Flood plain analysis for Petris, , Troas, and Monoros, tia watersheds, the Arad department, Romania

NASA Astrophysics Data System (ADS)

Győri, M.-M.; Haidu, I.

2012-04-01

The present study sets out to determine the flood plains corresponding to flood discharges having 10, 50 and 100 year recurrence intervals on the Monoroštia, Petriš and Troaš Rivers, located in Western Romania, the Arad department. The data of the study area is first collected and pre-processed in ArcGIS. It consists of land use data, soil data, the DEM, stream gauges' and meteorological stations' locations, on the basis of which the watersheds' hydrologic parameters' are computed using the Geospatial Hydrologic Modelling Extension (HEC Geo-HMS). HEC Geo-HMS functions as an interface between ArcGIS and HEC-HMS (Hydrologic Engineering Centre- Hydrologic Modelling System) and converts the data collected and generated in ArcGIS to data useable by HEC-HMS. The basin model component in HEC-HMS represents the physical watershed. It facilitates the effective rainfall computation on the basis of the input hyetograph, passing the results to a transform function that converts the excess precipitation into runoff at the subwatersheds' outlet. This enables the estimation and creation of hydrographs for the ungauged watersheds. In the present study, the results are achieved through the SCS CN loss method and the SCS Unit hydrograph transform method. The simulations use rainfall data that is registered at the stations situated in the catchments' vicinity, data that spans over two decades (1989-2009) and which allows the rainfall hyetographs to be determined for the above mentioned return periods. The model will be calibrated against measured streamflow data from the gauging stations on the main rivers, leading to the adjustment of watershed parameters, such as the CN parameter. As the flood discharges for 10, 50 and 100 year return periods have been determined, the profile of the water surface elevation along the channel will be computed through a steady flow analysis, with HEC-RAS (Hydrologic Engineering Centre- River Analysis System). For each of the flood frequencies, a water surface TIN is generated and intersected with the DEM in order to create the flood plain polygons. The final result consists of the flood plain delineation and the water inundation depths for the 10, 50 and 100 year return period flood events. These could be further employed in a risk assessment. Key words : flood plain analysis, frequency analysis, HEC-HMS, HEC-RAS. Aknowledgements This work was possible with the financial support of the Sectoral Operational Programme for Human Resources Development 2007-2013, co-financed by the European Social Fund, under the project number POSDRU/107/1.5/S/76841 with the title "Modern Doctoral Studies: Internationalization and Interdisciplinarity".

Model Integration for Real-Time Flood Forecasting Inundation Mapping for Nashville Tributaries

NASA Astrophysics Data System (ADS)

Charley, W.; Moran, B.; LaRosa, J.

2012-12-01

In May of 2010, between 14 and 19 inches of rain fell on the Nashville metro area in two days, quickly overwhelming tributaries to the Cumberland River and causing wide-spread, serious flooding. Tractor-trailers and houses were seen floating down Mill Creek, a primary tributary in the south eastern area of Nashville. Twenty-six people died and over 2 billion dollars in damage occurred as a result of the flood. Since that time, several other significant rainfall events have occurred in the area. Emergency responders were unable to deliver aid or preventive measures to areas under threat of flooding (or under water) in time to reduce damages because they could not identify those areas far enough in advance of the floods. Nashville Metro Water, the National Weather Service, the US Geological Survey and the US Army Corps of Engineers established a joint venture to seek ways to better forecast short-term flood events in the region. One component of this effort was a pilot project to compute and display real time inundation maps for Mill Creek, a 108 square-mile basin to the south east of Nashville. HEC-RTS (Real-Time Simulation) was used to assimilate and integrate the hydrologic model HEC-HMS with the hydraulics model HEC-RAS and the inundation mapping program HEC-RAS Mapper. The USGS, along with the other agencies, installed additional precipitation and flow/stage gages in the area. Measurements are recorded every 5-30 minutes and are posted on the USGS NWIS database, which are downloaded by HEC-RTS. Using this data in combination with QPFs (Quantitative Precipitation Forecasts) from the NWS, HEC-RTS applies HEC-HMS and HEC-RAS to estimate current and forecast stage hydrographs. The peak stages are read by HEC-RAS Mapper to compute inundation depths for 6 by 6 foot grid cells. HEC-RTS displays the inundation on a high resolution MrSid aerial photo, along with subbasin boundary, street and various other layers. When a user zooms in and "mouses" over a cell, the inundation depth for that cell is displayed as a tool-tip. This procedure for real-time inundation mapping provides a relatively accurate depiction of water depths throughout the basin, as it is computed using the temporal and spatial distribution of rainfall that has actually occurred and will compute depths based on forecasted rainfall. In addition, the HEC-RAS hydraulics model can be modified as the event is occurring to represent changes in the stream channels, such as obstructions at bridges. This paper covers the procedure used and provides results and images from the integrated models for various precipitation scenarios.

Estimation of Channel-Forming Discharge and Large-Event Geomorphic Response Using HEC-RAS

NASA Astrophysics Data System (ADS)

Hamilton, P.; Strom, K.; Hosseiny, S. M. H.

2015-12-01

The goal of the present work was to consider the functionality and applicability of HEC-RAS sediment transport simulations in two situations. The first was as a mode for obtaining quick estimates of the effective discharge, one measure of channel-forming discharge, and the second was as a mode to quickly estimate sediment transport and the commensurate potential erosion and deposition during large flood events. Though there are many other sediment transport and morphodynamic models available, e.g., CCHE1D, Nays2DH, we were interested in using HEC-RAS since this is the model of choice for many regulatory bodies, e.g., FEMA, cities, and counties. This makes using the sediment transport capability of HEC-RAS a natural extension of models that already otherwise exist and are well calibrated. In first looking at the utility of these models, we wanted to estimate the effective discharge of streams. Effective discharge is one way of defining the channel-forming discharge for a stream and is therefore an important parameter in natural channel design and restoration efforts. By running this range of floods, one can easily obtain an estimate for recurrence interval most responsible for moving the majority of sediment over a long time period. Results were compared to data collected within our research group on the Brazos River (TX). Effective discharge is an important estimate, particularly in understanding the equilibrium channel condition. Nevertheless, large floods are contemporaneously catastrophic and understanding their potential effects is desirable. Finally, we performed some sensitivity analysis to better understand the underlying assumptions of the various sediment transport model options and how they might affect the outcome of the aforementioned computations.

Antiemetic therapy in Asia Pacific countries for patients receiving moderately and highly emetogenic chemotherapy--a descriptive analysis of practice patterns, antiemetic quality of care, and use of antiemetic guidelines.

PubMed

Yu, Shiying; Burke, Thomas A; Chan, Alexandre; Kim, Hoon-Kyo; Hsieh, Ruey Kuen; Hu, Xichun; Liang, Jin-Tung; Baños, Ana; Spiteri, Carmel; Keefe, Dorothy M K

2015-01-01

This paper reports prescribing patterns for prophylaxis of chemotherapy-induced nausea and vomiting (CINV) after highly or moderately emetogenic chemotherapy (HEC or MEC) for cancer in six Asia Pacific countries. In a prospective noninterventional study, 31 sites in Australia, China, India, Singapore, South Korea, and Taiwan recorded details of CINV prophylaxis for the acute phase (first 24 h) and delayed phase (days 2-5) after single-day HEC or MEC for adult patients. Additional information on CINV prophylactic medications was collected from 6-day patient diaries. Primary antiemetic therapies were defined as corticosteroids, the 5-hydroxytryptamine-3 receptor antagonists (5HT3-RAs), and neurokinin-1 receptor antagonists (NK1-RAs). Evaluable patients in cycle 1 numbered 648 (318 [49%] HEC and 330 [51%] MEC) of mean (SD) age of 56 (12) years, including 58% women. For the acute phase after HEC, overall (and country range), 96% (91-100%) of patients received a 5HT3-RA, 87% (70-100%) a corticosteroid, and 43% (0-91%) an NK1-RA. CINV prophylaxis for the HEC delayed phase was more variable: including 22% (7-65%) 5HT3-RA, 52% (12-93%) corticosteroid, and 46% (0-88%) NK1-RA. For the MEC acute phase, 97% (87-100%) of patients received 5HT3-RA and 86% (73-97%) a corticosteroid. For the MEC delayed phase, 201 patients (61%) received a primary antiemetic, including 5HT3-RA (41%), corticosteroid (37%), and/or NK1-RA (4%). The 5HT3-RAs were prescribed consistently in all countries, while prescribing of other antiemetic therapies was variable, and corticosteroids were under-prescribed for CINV prophylaxis, particularly in the delayed phase.

River analysis and floodplain modeling using HEC-GeoRAS/RAS, GIS and ArcGIS: a case study for the Salinas River

NASA Astrophysics Data System (ADS)

Mishra, P. K.; Bernini Campos, H. E.

2016-12-01

The lower portion of the Salinas River in Monterey bay, California has a history of flood, lots of study has been made ab out the water quality since the river provides water for the crops around, but is still in need a detailed study about the river behavior and flood analysis. The floods did significant damage, affecting valuable landing farms, residences and businesses in Monterey County. The first step for this study is comprehend and collect the river bathymetry and surroundings and then analyze the discharge and how it is going to change with time. This thesis develops a model about the specific site, recruiting real data from GIS and performing a flow simulation according to flow data provided by USGS, to verify water surface elevation and floodplain. The ArcMap, developed by ESRI, was used along with an extension (HEC-GeoRAS) because it was indeed the most appropriate model to work with the Digital Elevation Model, develop the floodplain and characterizing the land surface accurately in the study site. The HEC-RAS software, developed by US Army Corp of Engineers, was used to compute one-dimension steady flow and two-dimension unsteady flow, providing flow velocity, water surface elevation and profiles, total surface area, head and friction loss and other characteristics, allowing the analysis of the flow. A mean discharge, a mean peak streamflow and a peak discharge were used for the steady flow and a Hydrograph was used for the unsteady flow, both are based on the 1995 flood and discharge history. This study provides important information about water surface elevation and water flow, allowing stakeholders and the government to analyze solutions to avoid damage to the society and landowners.

Physical Model Study of Cross Vanes and Ice

DTIC Science & Technology

2009-08-01

spacing since, in the pre-scour state, experiments and the HEC - RAS hydraulic model (USACE 2002b) found that water surface ele- vation merged with the...docs/eng-manuals/em1110- 2-1612/toc.htm. USACE (2002b) HEC - RAS , Hydraulic Reference Manual. US Army Corps of Engineers Hydrologic Engineering Center...Currently little design guidance is available for constructing these structures on ice-affected rivers . This study used physical and numerical

HEC-RAS 2.2 for backwater and scour analysis - phase one

DOT National Transportation Integrated Search

2000-09-01

The Kansas Department of Transportation (KDOT) and most bridge consultants in Kansas have been using the DOS-WSPRO program and the KDOT scour spreadsheets to perform bridge hydraulics and scour analysis for the past several years. Unfortunately, DOS-...

Hydraulic Characteristics of Bedrock Constrictions and Evaluation of One- and Two-Dimensional Models of Flood Flow on the Big Lost River at the Idaho National Engineering and Environmental Laboratory, Idaho

USGS Publications Warehouse

Berenbrock, Charles; Rousseau, Joseph P.; Twining, Brian V.

2007-01-01

A 1.9-mile reach of the Big Lost River, between the Idaho National Engineering and Environmental Laboratory (INEEL) diversion dam and the Pioneer diversion structures, was investigated to evaluate the effects of streambed erosion and bedrock constrictions on model predictions of water-surface elevations. Two one-dimensional (1-D) models, a fixed-bed surface-water flow model (HEC-RAS) and a movable-bed surface-water flow and sediment-transport model (HEC-6), were used to evaluate these effects. The results of these models were compared to the results of a two-dimensional (2-D) fixed-bed model [Transient Inundation 2-Dimensional (TRIM2D)] that had previously been used to predict water-surface elevations for peak flows with sufficient stage and stream power to erode floodplain terrain features (Holocene inset terraces referred to as BLR#6 and BLR#8) dated at 300 to 500 years old, and an unmodified Pleistocene surface (referred to as the saddle area) dated at 10,000 years old; and to extend the period of record at the Big Lost River streamflow-gaging station near Arco for flood-frequency analyses. The extended record was used to estimate the magnitude of the 100-year flood and the magnitude of floods with return periods as long as 10,000 years. In most cases, the fixed-bed TRIM2D model simulated higher water-surface elevations, shallower flow depths, higher flow velocities, and higher stream powers than the fixed-bed HEC-RAS and movable-bed HEC-6 models for the same peak flows. The HEC-RAS model required flow increases of 83 percent [100 to 183 cubic meters per second (m3/s)], and 45 percent (100 to 145 m3/s) to match TRIM2D simulations of water-surface elevations at two paleoindicator sites that were used to determine peak flows (100 m3/s) with an estimated return period of 300 to 500 years; and an increase of 13 percent (150 to 169 m3/s) to match TRIM2D water-surface elevations at the saddle area that was used to establish the peak flow (150 m3/s) of a paleoflood with a return period of 10,000 years. A field survey of the saddle area, however, indicated that the elevation of the lowest point on the saddle area was 1.2 feet higher than indicated on the 2-ft contour map that was used in the TRIM2D model. Because of this elevation discrepancy, HEC-RAS model simulations indicated that a peak flow of at least 210 m3/s would be needed to initiate flow across the 10,000-year old Pleistocene surface. HEC-6 modeling results indicated that to compensate for the effects of streambed scour, additional flow increases would be needed to match HEC-RAS and TRIM2D water-surface elevations along the upper and middle reaches of the river, and to compensate for sediment deposition, a slight decrease in flows would be needed to match HEC-RAS water-surface elevations along the lower reach of the river. Differences in simulated water-surface elevations between the TRIM2D and the HEC-RAS and HEC-6 models are attributed primarily to differences in topographic relief and to differences in the channel and floodplain geometries used in these models. Topographic differences were sufficiently large that it was not possible to isolate the effects of these differences on simulated water-surface elevations from those attributable to the effects of supercritical flow, streambed scour, and sediment deposition.

Applying 1D Sediment Models to Reservoir Flushing Studies: Measuring, Monitoring, and Modeling the Spencer Dam Sediment Flush with HEC-RAS

DTIC Science & Technology

2016-07-01

approximately 5 hours (hr) after opening main gates. Multiple channels eroded (Figure 5), moving sediment through the dam throughout the first day...additional sediment evacuation was observed over the next 4 weeks. ERDC/CHL CHETN-XIV-52 July 2016 5 Figure 5. Multiple channels eroded...2015. A physically-based channel - modeling framework integrating HEC-RAS sediment transport capabilities and the USDA-ARS Bank-Stability and Toe-Erosion

Independent technical review and analysis of hydraulic modeling and hydrology under low-flow conditions of the Des Plaines River near Riverside, Illinois

USGS Publications Warehouse

Over, Thomas M.; Straub, Timothy D.; Hortness, Jon E.; Murphy, Elizabeth A.

2012-01-01

The U.S. Geological Survey (USGS) has operated a streamgage and published daily flows for the Des Plaines River at Riverside since Oct. 1, 1943. A HEC-RAS model has been developed to estimate the effect of the removal of Hofmann Dam near the gage on low-flow elevations in the reach approximately 3 miles upstream from the dam. The Village of Riverside, the Illinois Department of Natural Resources-Office of Water Resources (IDNR-OWR), and the U. S. Army Corps of Engineers-Chicago District (USACE-Chicago) are interested in verifying the performance of the HEC-RAS model for specific low-flow conditions, and obtaining an estimate of selected daily flow quantiles and other low-flow statistics for a selected period of record that best represents current hydrologic conditions. Because the USGS publishes streamflow records for the Des Plaines River system and provides unbiased analyses of flows and stream hydraulic characteristics, the USGS served as an Independent Technical Reviewer (ITR) for this study.

Using HEC-RAS to Enhance Interpretive Capabilities of Geomorphic Assessments

NASA Astrophysics Data System (ADS)

Keefer, L. L.

2005-12-01

The purpose of a geomorphic assessment is to characterize and evaluate a fluvial system for determining the past watershed and channel conditions, current geomorphic character and potential future channel adjustments. The geomorphic assessment approach utilized by the Illinois State Water Survey assesses channel response to disturbance at multiple temporal and spatial scales to help identify the underlying factors and events which led to the existing channel morphology. This is accomplished through two phases of investigation that involve a historical and physical analysis of the watershed, disturbance history, and field work at increasing levels of detail. To infer future channel adjustments, the geomorphic assessment protocol combines two methods of analyses that are dependent on the quantity and detail of the available data. The first method is the compilation of multiple lines of evidence using qualitative information related to the dominant fluvial environment, channel gradient, stream power thresholds, and channel evolution models. The second method is the use of hydraulic models which provide additional interpretative skills to evaluate potential channel adjustments. The structured data collection framework of the geomorphic assessment approach is used for the development of a HEC-RAS model. The model results are then used as another tool to determine the influence of bridges and control structures on channel stability, stream power profiles to identify potential channel bed degradation zones, and provide data for physically-based bank stability models. This poster will demonstrate the advantages of using a hydraulic model, such as HEC-RAS, to expand the interpretive capabilities of geomorphic assessments. The results from applying this approach will be demonstrated for the Big Creek watershed of the Cache River Basin in southern Illinois.

Prevention of chemotherapy-induced nausea: the role of neurokinin-1 (NK1) receptor antagonists.

PubMed

Bošnjak, Snežana M; Gralla, Richard J; Schwartzberg, Lee

2017-05-01

Chemotherapy-induced nausea (CIN) has a significant negative impact on the quality of life of cancer patients. The use of 5-hydroxytryptamine-3 (5-HT 3 ) receptor antagonists (RAs) has reduced the risk of vomiting, but (except for palonosetron) their effect on nausea, especially delayed nausea, is limited. This article reviews the role of NK 1 RAs when combined with 5-HT 3 RA-dexamethasone in CIN prophylaxis. Aprepitant has not shown consistent superiority over a two-drug (ondansetron-dexamethasone) combination in nausea control after cisplatin- or anthracycline-cyclophosphamide (AC)-based highly emetogenic chemotherapy (HEC). Recently, dexamethasone and dexamethasone-metoclopramide were demonstrated to be non-inferior to aprepitant and aprepitant-dexamethasone, respectively, for the control of delayed nausea after HEC (AC/cisplatin), and are now recognized in the guidelines. The potential impact of the new NK 1 RAs rolapitant and netupitant (oral fixed combination with palonosetron, as NEPA) in CIN prophylaxis is discussed. While the clinical significance of the effect on nausea of the rolapitant-granisetron-dexamethasone combination after cisplatin is not conclusive, rolapitant addition showed no improvement in nausea prophylaxis after AC or moderately emetogenic chemotherapy (MEC). NEPA was superior to palonosetron in the control of nausea after HEC (AC/cisplatin). Moreover, the efficacy of NEPA in nausea control was maintained over multiple cycles of HEC/MEC. Recently, NK 1 RAs have been challenged by olanzapine, with olanzapine showing superior efficacy in nausea prevention after HEC. Fixed antiemetic combinations (such as NEPA) or new antiemetics with a long half-life that may be given once per chemotherapy cycle (rolapitant or NEPA) may improve patient compliance with antiemetic treatment.

Integrating Satellite Image Identification and River Routing Simulation into the Groundwater Simulation of Chou-Shui Basin

NASA Astrophysics Data System (ADS)

Yao, Y.; Yang, S.; Chen, Y.; Chang, L.; Chiang, C.; Huang, C.; Chen, J.

2012-12-01

Many groundwater simulation models have been developed for Chou-Shui River alluvial fan which is one of the most important groundwater areas in Taiwan. However, the exchange quantity between Chou-Shui River, the major river in this area, and the groundwater system itself is seldom studied. In this study, the exchange is evaluated using a river package (RIV) in the groundwater simulation model, MODFLOW 2000. Several critical parameters and variables used in RIV such as wet area and river level for each cell below the Chou-Shui River are respectively determined by satellite image identification and HEC-RAS simulation. The monthly average of river levels obtained from four stations include Chang-Yun Bridge, Xi-Bin Bridge, Chi-Chiang Bridge and Si-Jou Bridge during 2008 and the river cross-section measured on December 2007 are used in the construction of HEC-RAS model. Four FORMOSAT multispectral satellite images respectively obtained on January 2008, April 2008, July 2008, and November 2008 are used to identify the wet area of Chou-Shui River during different seasons. Integrating the simulation level provided by HEC-RAS and the identification result are used as the assignment of RIV. First, based on the simulation results of HEC-RAS, the water level differences between flooding period and draught period are 1.4 (m) and 2.0 (m) for Xi-Bin Bridge station (downstream) and Chang-Yun Bridge station (upstream) respectively. Second, based on the identified results, the wet areas for four seasons are 24, 24, 40 and 12 (km2) respectively. The variation range of areas in 2008 is huge that the area for winter is just 30% of the area for summer. Third, based on the simulation of MODFLOW 2000 and RIV, the exchange between the river and the groundwater system is 414 million cubic meters which contains 526 for recharge to river and 112 for discharging from river during 2008. The total recharge includes river exchange and recharge from non-river area is 2023 million cubic meters. The pumping quantity is 1930 million cubic meters.

Remediation scenarios for attenuating peak flows and reducing sediment transport in Fountain Creek, Colorado, 2013

USGS Publications Warehouse

Kohn, Michael S.; Fulton, John W.; Williams, Cory A.; Stogner, Sr., Robert W.

2014-01-01

The U.S. Geological Survey (USGS) in cooperation with the Fountain Creek Watershed, Flood Control and Greenway District assessed remediation scenarios to attenuate peak flows and reduce sediment loads in the Fountain Creek watershed. To evaluate these strategies, the U.S. Army Corps of Engineers Hydrologic Engineering Center (HEC) hydrologic and hydraulic models were employed. The U.S. Army Corps of Engineers modeling system HEC-HMS (Hydrologic Modeling System) version 3.5 was used to simulate runoff in the Fountain Creek watershed, Colorado, associated with storms of varying magnitude and duration. Rain-gage precipitation data and radar-based precipitation data from the April 28–30, 1999, and September 14–15, 2011, storm events were used in the calibration process for the HEC-HMS model. The curve number and lag time for each subwatershed and Manning's roughness coefficients for each channel reach were adjusted within an acceptable range so that the simulated and measured streamflow hydrographs for each of the 12 USGS streamgages approximated each other. The U.S. Army Corps of Engineers modeling system HEC-RAS (River Analysis System) versions 4.1 and 4.2 were used to simulate streamflow and sediment transport, respectively, for the Fountain Creek watershed generated by a particular storm event. Data from 15 USGS streamgages were used for model calibration and 7 of those USGS streamgages were used for model validation. The calibration process consisted of comparing the simulated water-surface elevations and the cross-section-averaged velocities from the model with those surveyed in the field at the cross section at the corresponding 15 and 7 streamgages, respectively. The final Manning’s roughness coefficients were adjusted between –30 and 30 percent at the 15 calibration streamgages from the original left, right, and channel-averaged Manning's roughness coefficients upon completion of calibration. The U.S. Army Corps of Engineers modeling system HEC-RAS version 4.2 was used to simulate streamflow and sediment transport for the Fountain Creek watershed generated by a design-storm event. The Laursen-Copeland sediment-transport function was used in conjunction with the Exner 5 sorting method and the Ruby fall-velocity method to predict sediment transport. Six USGS streamgages equipped with suspended-sediment samplers were used to develop sediment-flow rating curves for the sediment-transport-model calibration. The critical Shields number in the Laursen-Copeland sediment-transport function and the volume of sediment available at a given cross section were adjusted during the HEC-RAS sediment-model calibration process. HEC-RAS model simulations used to evaluate the 14 remediation scenarios were based on unsteady-state streamflows associated with a 24-hour, 1-percent annual exceedance probability (100-year) National Oceanic and Atmospheric Administration Type II precipitation event. Scenario 0 represents the baseline or current conditions in the watershed and was used to compare the remaining 13 scenarios. Scenarios 1–8 and 12 rely on side-detention facilities to reduce peak flows and sediment transport. Scenario 9 has a diversion channel, and scenario 10 has a reservoir. Scenarios 11 and 13 incorporate channel armoring and channel widening, respectively. Scenarios 8 and 10, the scenario with the most side-detention facilities, and the scenario with the reservoir, respectively, were the most effective at reducing sediment transport and peak flow at the Pueblo, Colorado, streamgage. Scenarios 8 and 10 altered the peak flow by –58.9 and –56.4 percent, respectively. In turn, scenarios 8 and 10 altered the sediment transport by –17.7 and –62.1 percent, respectively.

Impact of 5-HT(3) RA selection within triple antiemetic regimens on uncontrolled highly emetogenic chemotherapy-induced nausea/vomiting.

PubMed

Schwartzberg, Lee; Jackson, James; Jain, Gagan; Balu, Sanjeev; Buchner, Deborah

2011-08-01

It is recommended that patients initiate triple antiemetic therapy with one of the 5-hydroxytryptamine receptor antagonists (5-HT(3) RAs), aprepitant (or its intravenous prodrug fosaprepitant) and dexamethasone prior to the start of highly emetogenic chemotherapy (HEC). However, the impact of 5-HT(3) RA selection within triple antiemetic regimens on the risk of uncontrolled chemotherapy-induced nausea and vomiting (CINV) with HEC has not been well studied. To assess the likelihood of an uncontrolled CINV event following antiemetic prophylaxis with the 5-HT(3) RA palonosetron + aprepitant/fosaprepitant + dexamethasone (palonosetron cohort) versus any of the other 5-HT(3) RAs + aprepitant/fosaprepitant + dexamethasone (other 5-HT(3) RA cohort) among single-day HEC cycles. Single-day HEC cycles (a gap of at least 5 days between two administrations) among patients with a cancer diagnosis and receiving antiemetic prophylaxis with the aforementioned regimens between 1/1/2006 and 6/30/2010 were identified from the IMS LifeLink claims database. Uncontrolled CINV events were identified through ICD-9-CM codes (nausea and vomiting), Current Procedural Terminology codes (hydration), rescue medications and/or use of antiemetic therapy from days 2-5 following HEC administration. Risks for an uncontrolled CINV event among all patients, and within breast cancer and multiple cancer subpopulations, were analyzed at cycle level using logistic multivariate regression models. A total of 8018 cycles for the palonosetron cohort and 1926 cycles for the other 5-HT(3) RA cohort (3574 and 978 patients, respectively) were analyzed. Single-day HEC cycles received by the palonosetron cohort had a significantly lower unadjusted risk of an uncontrolled CINV event (17.5 vs 20.7% for the other 5-HT(3) RA cohort; p = 0.0010), with a 17% lower adjusted risk for palonosetron-administered cycles (odds ratio: 0.83; 95% CI: 0.73-0.94; p = 0.0042). Results in the breast cancer and multiple cancer subgroups were consistent with those for the overall population. In this retrospective claims data analysis, single-day HEC cycles administered with palonosetron + aprepitant/fosaprepitant + dexamethasone had a lower risk for an uncontrolled CINV event versus other 5-HT(3) RAs + aprepitant/fosaprepitant + dexamethasone.

Numerical modeling of rapidly varying flows using HEC-RAS and WSPG models.

PubMed

Rao, Prasada; Hromadka, Theodore V

2016-01-01

The performance of two popular hydraulic models (HEC-RAS and WSPG) for modeling hydraulic jump in an open channel is investigated. The numerical solutions are compared with a new experimental data set obtained for varying channel bottom slopes and flow rates. Both the models satisfactorily predict the flow depths and location of the jump. The end results indicate that the numerical models output is sensitive to the value of chosen roughness coefficient. For this application, WSPG model is easier to implement with few input variables.

The HEC RAS model of regulated stream for purposes of flood risk reduction

NASA Astrophysics Data System (ADS)

Fijko, Rastislav; Zeleňáková, Martina

2016-06-01

The work highlights the modeling of water flow in open channels using 1D mathematical model HEC-RAS in the area of interest Lopuchov village in eastern Slovakia. We created a digital model from a geodetic survey, which was used to show the area of inundation in ArcGIS software. We point out the modeling methodology with emphasis to collection of the data and their relevance for determination of boundary conditions in 3D model of the study area in GIS platform. The BIM objects can be exported to the defined model of the area. The obtained results were used for simulation of flooding. The results give to us clearly and distinctly defined areas of inundation, which we used in the processing of Cost benefit analysis. We used the developed model for stating the potential damages in flood vulnerable areas.

Flood Risk and Asset Management

DTIC Science & Technology

2011-06-15

Model cascade could include HEC - RAS , HR BREACH and Dynamic RFSM. Action HRW to consider model coupling and advise DM. It was felt useful to...simple loss of life approach. WL can provide input and advise on USACE LIFESIM approaches. To enable comparison with HEC FRM approaches, it was

Comparison of new generation low-complexity flood inundation mapping tools with a hydrodynamic model

NASA Astrophysics Data System (ADS)

Afshari, Shahab; Tavakoly, Ahmad A.; Rajib, Mohammad Adnan; Zheng, Xing; Follum, Michael L.; Omranian, Ehsan; Fekete, Balázs M.

2018-01-01

The objective of this study is to compare two new generation low-complexity tools, AutoRoute and Height Above the Nearest Drainage (HAND), with a two-dimensional hydrodynamic model (Hydrologic Engineering Center-River Analysis System, HEC-RAS 2D). The assessment was conducted on two hydrologically different and geographically distant test-cases in the United States, including the 16,900 km2 Cedar River (CR) watershed in Iowa and a 62 km2 domain along the Black Warrior River (BWR) in Alabama. For BWR, twelve different configurations were set up for each of the models, including four different terrain setups (e.g. with and without channel bathymetry and a levee), and three flooding conditions representing moderate to extreme hazards at 10-, 100-, and 500-year return periods. For the CR watershed, models were compared with a simplistic terrain setup (without bathymetry and any form of hydraulic controls) and one flooding condition (100-year return period). Input streamflow forcing data representing these hypothetical events were constructed by applying a new fusion approach on National Water Model outputs. Simulated inundation extent and depth from AutoRoute, HAND, and HEC-RAS 2D were compared with one another and with the corresponding FEMA reference estimates. Irrespective of the configurations, the low-complexity models were able to produce inundation extents similar to HEC-RAS 2D, with AutoRoute showing slightly higher accuracy than the HAND model. Among four terrain setups, the one including both levee and channel bathymetry showed lowest fitness score on the spatial agreement of inundation extent, due to the weak physical representation of low-complexity models compared to a hydrodynamic model. For inundation depth, the low-complexity models showed an overestimating tendency, especially in the deeper segments of the channel. Based on such reasonably good prediction skills, low-complexity flood models can be considered as a suitable alternative for fast predictions in large-scale hyper-resolution operational frameworks, without completely overriding hydrodynamic models' efficacy.

An Assessment of Hydrology, Fluvial Geomorphology, and Stream Ecology in the Cardwell Branch Watershed, Nebraska, 2003-04

USGS Publications Warehouse

Rus, David L.; Dietsch, Benjamin J.; Woodward, Brenda K.; Fry, Beth E.; Wilson, Richard C.

2007-01-01

An assessment of the 16.3-square-mile Cardwell Branch watershed characterized the hydrology, fluvial geomorphology, and stream ecology in 2003-04. The study - performed by the U.S. Geological Survey in cooperation with the City of Lincoln, Nebraska, and the Lower Platte South Natural Resources District - focused on the 7.7-square-mile drainage downstream from Yankee Hill Reservoir. Hydrologic and hydraulic models were developed using the Hydrologic Modeling System (HEC-HMS) and River Analysis System (HEC-RAS) of the U.S. Army Corps of Engineers Hydraulic Engineering Center. Estimates of streamflow and water-surface elevation were simulated for 24-hour-duration design rainstorms ranging from a 50-percent frequency to a 0.2-percent frequency. An initial HEC-HMS model was developed using the standardized parameter estimation techniques associated with the Soil Conservation Service curve number technique. An adjusted HEC-HMS model also was developed in which parameters were adjusted in order for the model output to better correspond to peak streamflows estimated from regional regression equations. Comparisons of peak streamflow from the two HEC-HMS models indicate that the initial HEC-HMS model may better agree with the regional regression equations for higher frequency storms, and the adjusted HEC-HMS model may perform more closely to regional regression equations for larger, rarer events. However, a lack of observed streamflow data, coupled with conflicting results from regional regression equations and local high-water marks, introduced considerable uncertainty into the model simulations. Using the HEC-RAS model to estimate water-surface elevations associated with the peak streamflow, the adjusted HEC-HMS model produced average increases in water-surface elevation of 0.2, 1.1, and 1.4 feet for the 50-, 1-, and 0.2-percent-frequency rainstorms, respectively, when compared to the initial HEC-HMS model. Cross-sectional surveys and field assessments conducted between November 2003 and March 2004 indicated that Cardwell Branch and its unnamed tributary appear to be undergoing incision (the process of downcutting) (with three locations showing 2 or more feet of streambed incision since 1978) that is somewhat moderated by the presence of grade controls and vegetation along the channel profile. Although streambank failures were commonly observed, 96 percent of the surveyed cross sections were classified as stable by planar and rotational failure analysis-a disconnect that may have been the result of assumed soil properties. Two process-based classification systems each indicated that the reaches within the study area were incising and widening, and the Rosgen classification system characterized the streams as either type E6 or B6c. E6 channels are hydraulically efficient with low width-depth ratios, low to moderate sinuosity, and gentle to moderately steep slopes. B6c channels typically are incised with low width-depth ratios maintained by riparian vegetation, low bedload transport, and high washload transport. No obvious nickpoints (interruption or break in slope) were observed in the thalweg profile (line of maximum streambed descent), and the most acute incision occurred immediately downstream from bridges and culverts. Nine water-quality samples were collected between August 2003 and November 2004 near the mouth of the watershed. Sediment-laden rainfall-runoff substantially affected the water quality in Cardwell Branch, leading to greater biochemical and chemical oxygen demands as well as increased concentrations of several nutrient, bacteriological, sediment, and pesticide constituents. The storage of rainfall runoff in Yankee Hill Reservoir may prolong the presence of runoff-related constituents downstream. Across the study area, there was a lack of habitat availability for aquatic biota because of low dissolved oxygen levels and low streamflows or dry channels. In August 2003, the aquatic community near the mouth of

The Cumberland River Flood of 2010 and Corps Reservoir Operations

NASA Astrophysics Data System (ADS)

Charley, W.; Hanbali, F.; Rohrbach, B.

2010-12-01

On Saturday, May 1, 2010, heavy rain began falling in the Cumberland River Valley and continued through the following day. 13.5 inches was measured at Nashville, an unprecedented amount that doubled the previous 2-day record, and exceeded the May monthly total record of 11 inches. Elsewhere in the valley, amounts of over 19 inches were measured. The frequency of this storm was estimated to exceed the one-thousand year event. This historic rainfall brought large scale flooding to the Cumberland-Ohio-Tennessee River Valleys, and caused over 2 billion dollars in damages, despite the numerous flood control projects in the area, including eight U.S. Army Corps of Engineers projects. The vast majority of rainfall occurred in drainage areas that are uncontrolled by Corps flood control projects, which lead to the wide area flooding. However, preliminary analysis indicates that operations of the Corps projects reduced the Cumberland River flood crest in Nashville by approximately five feet. With funding from the American Recovery and Reinvestment Act (ARRA) of 2009, hydrologic, hydraulic and reservoir simulation models have just been completed for the Cumberland-Ohio-Tennessee River Valleys. These models are being implemented in the Corps Water Management System (CWMS), a comprehensive data acquisition and hydrologic modeling system for short-term decision support of water control operations in real time. The CWMS modeling component uses observed rainfall and forecasted rainfall to compute forecasts of river flows into and downstream of reservoirs, using HEC-HMS. Simulation of reservoir operations, utilizing either the HEC-ResSim or CADSWES RiverWare program, uses these flow scenarios to provide operational decision information for the engineer. The river hydraulics program, HEC-RAS, computes river stages and water surface profiles for these scenarios. An inundation boundary and depth map of water in the flood plain can be calculated from the HEC-RAS results using ArcInfo. The economic impacts of the different inundation depths are computed by HEC-FIA. The user-configurable sequence of modeling software allows engineers to evaluate operational decisions for reservoirs and other control structures, and view and compare hydraulic and economic impacts for various “what if?” scenarios. This paper reviews the Cumberland River May 2010 event, the impact of Corps reservoirs and reservoir operations and the expected future benefits and effects of the ARRA funded models and CWMS on future events for this area.

Managing water and riparian habitats on the Bill Williams River with scientific benefit for other desert river systems

USGS Publications Warehouse

John Hickey,; Woodrow Fields,; Andrew Hautzinger,; Steven Sesnie,; Shafroth, Patrick B.; Dick Gilbert,

2016-01-01

This report details modeling to: 1) codify flow-ecology relationships for riparian species of the Bill Williams River as operational guidance for water managers, 2) test the guidance under different climate scenarios, and 3) revise the operational guidance as needed to address the effects of climate change. Model applications detailed herein include the River Analysis System  (HEC-RAS) and the Ecosystem Functions Model  (HEC-EFM), which was used to generate more than three million estimates of local seedling recruitment areas. Areas were aggregated and compared to determine which scenarios generated the most seedling area per unit volume of water. Scenarios that maximized seedling area were grouped into a family of curves that serve as guidance for water managers. This work has direct connections to water management decision-making and builds upon and adds to the rich history of science-based management for the Bill Williams River, Arizona, USA. 

Characterizing coarse bedload transport during floods with RFID and accelerometer tracers, in-stream RFID antennas and HEC-RAS modeling

NASA Astrophysics Data System (ADS)

Olinde, L.; Johnson, J. P.

2013-12-01

By monitoring the transport timing and distances of tracer grains in a steep mountains stream, we collected data that can constrain numerical bedload transport models considered for these systems. We captured bedload activity during a weeks-spanning snowmelt period in Reynolds Creek, Idaho by deploying Radio Frequency Identification (RFID) and accelerometer embedded tracers with in-stream stationary RFID antennas. During transport events, RFID dataloggers recorded the times when tracers passed over stationary antennas. The accelerometer tracers also logged x, y, z-axis accelerations every 10 minutes to identify times of motion and rest. After snowmelt flows receded, we found tracers with mobile antennas and surveyed their positions. We know the timing and tracer locations when accelerometer tracers were initially entrained, passed stationary antennas, and were finally deposited at the surveyed locations. The fraction of moving accelerometers over time correlates well with discharge. Comparisons of the transported tracer fraction between rising and falling limbs over multiple flood peaks suggest that some degree of clockwise hysteresis persisted during the snowmelt period. Additionally, we apply accelerometer transport durations and displacement distances to calculate virtual velocities over full tracer path lengths and over lengths between initial locations to stationary antennas as well as between stationary antennas to final positions. The accelerometer-based virtual velocities are significantly faster than those estimated from traditional tracer methods that estimate bedload transport durations by assuming threshold flow conditions. We also subsample the motion data to calculate how virtual velocities change over the measurement intervals. Regressions of these relations are in turn used to extrapolate virtual velocities at smaller sampling timescales. Minimum hop lengths are also evaluated for each accelerometer tracer. Finally, flow conditions during the snowmelt hydrograph are modeled over the 11 kilometers of surveyed stream by utilizing 1m airborne LiDAR and HEC-GeoRAS. Cross-sectional HEC-RAS results are used to estimate the spatial distribution of longitudinal shear velocities over the observed discharges. At final accelerometer tracer positions, we analyze the HEC-RAS generated flow conditions for each disentrainment discharge magnitude. The techniques developed here have the potential to link individual grain characteristics during floods to a range of time and length scales.

A physically-based channel-modeling framework integrating HEC-RAS sediment transport capabilities and the USDA-ARS bank-stability and toe-erosion model (BSTEM)

USDA-ARS?s Scientific Manuscript database

Classical, one-dimensional, mobile bed, sediment-transport models simulate vertical channel adjustment, raising or lowering cross-section node elevations to simulate erosion or deposition. This approach does not account for bank erosion processes including toe scour and mass failure. In many systems...

Flood Discharge Analysis with Nakayasu Method Using Combination of HEC-RAS Method on Deli River in Medan City

NASA Astrophysics Data System (ADS)

Harahap, Rumilla; Jeumpa, Kemala; Hadibroto, Bambang

2018-03-01

The problem in this research is how in the rainy season the water does not overflow, does not occur flood and during the dry season does not occur drought so it can adjust the condition or existence of Deli river which is around Medan city. Deli River floods often occur, either caused by a smaller capacity than the existing discharge, lack of maintenance and drainage and disposal systems that do not fit with the environment, resulting in flood subscriptions every year. The purpose of this research is to know flood discharge at Deli river as Flood control in Medan city. This research is analyzed on several methods such as log Pearson, Gumbel and hydrograph unit, while HEC-RAS method is modeling conducted in analyzing the water profile of the Deli River. Furthermore, the calculation of the periodic flood discharge using the Nakayasu Method. Calculation result at Deli River return period flood discharge 2 years with an area of 14.8 km2 annual flood hydrograph the total is 26.79 m3/sec on the hours at the 4th time. Return period flood discharge 5 years with an area of 14.8 km2 annual flood hydrograph the total is 73,44 m3/sec. While 25 annual return period total flood hydrograph is 146.50 m3/sec. With flood analysis can reduce and minimize the risk of losses and land can be mapped if in the area there is flooding.

Methodology for predicting maximum velocity and shear stress in a sinuous channel with bendway weirs using 1-D HEC-RAS modeling results

Treesearch

Paul Sclafani; Christopher I. Thornton; Amanda L. Cox; Steven R. Abt

2012-01-01

As with every natural process, river morphology incorporates a complex and nuanced set of processes that combine to produce an infinite set of possible outcomes. Natural laws that govern natural systems cause rivers to react to changes in the environment in order to maintain equilibrium. Changes in hydraulics, sediment transport, and habitat help keep natural systems...

Palonosetron versus older 5-HT3 receptor antagonists for nausea prevention in patients receiving chemotherapy: a multistudy analysis

PubMed Central

Morrow, Gary R; Schwartzberg, Lee; Barbour, Sally Y; Ballinari, Gianluca; Thorn, Michael D; Cox, David

2015-01-01

Background No clinical standard currently exists for the optimal management of nausea induced by emetogenic chemotherapy, particularly delayed nausea. Objective To compare the efficacy and safety of palonosetron with older 5-HT3 receptor antagonists (RAs) in preventing chemotherapy-induced nausea. Methods Data were pooled from 4 similarly designed multicenter, randomized, double-blind, clinical trials that compared single intravenous doses of palonosetron 0.25 mg or 0.75 mg with ondansetron 32 mg, dolasetron 100 mg, or granisetron 40 μg/kg, administered 30 minutes before moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC). Pooled data within each chemotherapy category (MEC: n = 1,132; HEC: n = 1,781) were analyzed by a logistic regression model. Nausea endpoints were complete control rates (ie, no more than mild nausea, no vomiting, and no rescue medication), nausea-free rates, nausea severity, and requirement for rescue antiemetic/antinausea medication over 5 days following chemotherapy. Pooled safety data were summarized descriptively. Results Numerically more palonosetron-treated patients were nausea-free on each day, and fewer had moderate-severe nausea. Similarly, usage of rescue medication was less frequent among palonosetron-treated patients. Complete control rates for palonosetron and older 5-HT3 RAs in the acute phase were 66% vs 63%, 52% vs 42% in the delayed phase (24-120 hours), and 46% vs 37% in the overall phase. The incidence of adverse events was similar for palonosetron and older 5-HT3 RAs. Limitations This post hoc analysis summarized data for palonosetron and several other 5-HT3 RAs but was not powered for statistical comparisons between individual agents. Because nausea is inherently subjective, the reliability of assessments of some aspects (eg, severity) may be influenced by interindividual variability. Conclusion Palonosetron may be more effective than older 5-HT3 RAs in preventing nausea, with comparable tolerability. PMID:25830233

Uncertainty of the peak flow reconstruction of the 1907 flood in the Ebro River in Xerta (NE Iberian Peninsula)

NASA Astrophysics Data System (ADS)

Ruiz-Bellet, Josep Lluís; Castelltort, Xavier; Balasch, J. Carles; Tuset, Jordi

2017-02-01

There is no clear, unified and accepted method to estimate the uncertainty of hydraulic modelling results. In historical floods reconstruction, due to the lower precision of input data, the magnitude of this uncertainty could reach a high value. With the objectives of giving an estimate of the peak flow error of a typical historical flood reconstruction with the model HEC-RAS and of providing a quick, simple uncertainty assessment that an end user could easily apply, the uncertainty of the reconstructed peak flow of a major flood in the Ebro River (NE Iberian Peninsula) was calculated with a set of local sensitivity analyses on six input variables. The peak flow total error was estimated at ±31% and water height was found to be the most influential variable on peak flow, followed by Manning's n. However, the latter, due to its large uncertainty, was the greatest contributor to peak flow total error. Besides, the HEC-RAS resulting peak flow was compared to the ones obtained with the 2D model Iber and with Manning's equation; all three methods gave similar peak flows. Manning's equation gave almost the same result than HEC-RAS. The main conclusion is that, to ensure the lowest peak flow error, the reliability and precision of the flood mark should be thoroughly assessed.

Conservation Reserve Program effects on floodplain land cover management.

PubMed

Jobe, Addison; Kalra, Ajay; Ibendahl, Elise

2018-05-15

Growing populations and industrialized agriculture practices have eradicated much of the United States wetlands along river floodplains. One program available for the restoration of floodplains is the Conservation Reserve Program (CRP). The current research explores the effects CRP land change has on flooding zones, utilizing Flood Modeller and HEC-RAS. Flood Modeller is proven a viable tool for flood modeling within the United States when compared to HEC-RAS. Application of the software is used in the Nodaway River system located in the western halves of Iowa and Missouri to model effects of introducing new forest areas within the region. Flood stage during the conversion first decreases in the early years, before rising to produce greater heights. Flow velocities where CRP land is present are reduced for long-term scopes. Velocity reduction occurs as the Manning's roughness increases due to tree diameter and brush density. Flood zones become more widespread with the implementation of CRP. Future model implementations are recommended to witness the effects of smaller flood recurrence intervals. Copyright © 2018 Elsevier Ltd. All rights reserved.

Calibrating a hydraulic model using water levels derived from time series high-resolution Radarsat-2 synthetic aperture radar images and elevation data

NASA Astrophysics Data System (ADS)

Trudel, M.; Desrochers, N.; Leconte, R.

2017-12-01

Knowledge of water extent (WE) and level (WL) of rivers is necessary to calibrate and validate hydraulic models and thus to better simulate and forecast floods. Synthetic aperture radar (SAR) has demonstrated its potential for delineating water bodies, as backscattering of water is much lower than that of other natural surfaces. The ability of SAR to obtain information despite cloud cover makes it an interesting tool for temporal monitoring of water bodies. The delineation of WE combined with a high-resolution digital terrain model (DTM) allows extracting WL. However, most research using SAR data to calibrate hydraulic models has been carried out using one or two images. The objectives of this study is to use WL derived from time series high resolution Radarsat-2 SAR images for the calibration of a 1-D hydraulic model (HEC-RAS). Twenty high-resolution (5 m) Radarsat-2 images were acquired over a 40 km reach of the Athabasca River, in northern Alberta, Canada, between 2012 and 2016, covering both low and high flow regimes. A high-resolution (2m) DTM was generated combining information from LIDAR data and bathymetry acquired between 2008 and 2016 by boat surveying. The HEC-RAS model was implemented on the Athabasca River to simulate WL using cross-sections spaced by 100 m. An image histogram thresholding method was applied on each Radarsat-2 image to derive WE. WE were then compared against each cross-section to identify those were the slope of the banks is not too abrupt and therefore amenable to extract WL. 139 observations of WL at different locations along the river reach and with streamflow measurements were used to calibrate the HEC-RAS model. The RMSE between SAR-derived and simulated WL is under 0.35 m. Validation was performed using in situ observations of WL measured in 2008, 2012 and 2016. The RMSE between the simulated water levels calibrated with SAR images and in situ observations is less than 0.20 m. In addition, a critical success index (CSI) was performed to compare the WE simulated by HEC-RAS and that derived from SARs images. The CSI is higher than 0.85 for each date, which means that simulated WE is highly similar to the WE derived from SARs images. Thereby, the results of our analysis indicate that calibration of a hydraulic model can be performed from WL derived from time series of high-resolution SAR images.

The Anticancer Effects of Radachlorin-mediated Photodynamic Therapy in the Human Endometrial Adenocarcinoma Cell Line HEC-1-A.

PubMed

Kim, Su-Mi; Rhee, Yun-Hee; Kim, Jong-Soo

2017-11-01

We investigated the effect of photodynamic therapy (PDT) using radachlorin on invasion, vascular formation and apoptosis by targeting epidermal growth factor receptor (EGFR)/vascular endothelial growth factor receptor 2 (VEGFR2) signaling pathways in the HEC-1-A endometrial adenocarcinoma cell line. To investigate the apoptotic pathway, we performed the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay, and western blot analysis. We also evaluated the effects of PDT on tubular capillary formation in and invasion by HEC-1-A cells with a tube formation assay, invasion assay, prostaglandin E2 (PGE2) assay, and western blot analysis. PDT had anticancer effects on HEC-1-A through activation of the intrinsic pathway of apoptosis via caspase-9 and poly-(ADP-ribose) polymerase (PARP). PDT also inhibited tubular capillary formation in and invasion by HEC-1-A under VEGF pretreatment, that resulted from down-regulation of VEGFR2, EGFR, Ras homolog gene family/ member A (RhoA) and PGE2. These results are indicative of the specificity of radachlorin-mediated PDT to VEGF. The major advantage of radachlorin-mediated PDT is its selectivity for cancer tissue while maintaining adjacent normal endometrial tissue. Therefore, radachlorin-mediated PDT might offer high anticancer efficacy for endometrial adenocarcinoma and an especially useful modality for preserving fertility. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

A Study on Estimation on Flood Warning Trigger Rainfall in medium and small Stream Affected by Urban Effects

NASA Astrophysics Data System (ADS)

Youngseok, Song; Moojong, Park; JungHo, Lee; HeeSup, Lee

2013-04-01

As extreme floods occur frequently in recent years due to global climate changes, an in sudden local flooding of great volume and short duration is becoming the significant danger and loss of life and property in the Korean Peninsula as well as most parts of the world. The desire for living without hazardous damages grows these days, the city strategy to make the safer community has become an issue. Previously most of flood prevention efforts have been made for relatively large watersheds near to channel flow. However, as economical development and the expansion of city near medium and small stream, human casualty and property by flood occurs frequently. Therefore, to reduce the damage of human lives and property by flood, we develop an assessment method for flood warning trigger rainfall considering urban effect. Considering complex land use, HEC-HMS is used for rural area and SWMM is adopted for sewer networks runoff. And relationship between runoff and stream water level, HEC-RAS is accompanied with runoff results. Proposed flood warning trigger rainfall assessment method shows good agreement with gauged data and could be used for another case to mitigate damage. Acknowledgement: "This research was supported by a grant [NEMA-NH-2011-45] from the Natural Hazard Mitigation Research Group, National Emergency Management Agency of Korea." Keyword: HEC-HMS, HEC-RAS, critical precipitation, medium and small stream

Stream profile analysis using a step backwater model for selected reaches in the Chippewa Creek basin in Medina, Wayne, and Summit Counties, Ohio

USGS Publications Warehouse

Straub, David E.; Ebner, Andrew D.

2011-01-01

The USGS, in cooperation with the Chippewa Subdistrict of the Muskingum Watershed Conservancy District, performed hydrologic and hydraulic analyses for selected reaches of three streams in Medina, Wayne, Stark, and Summit Counties in northeast Ohio: Chippewa Creek, Little Chippewa Creek, and River Styx. This study was done to facilitate assessment of various alternatives for mitigating flood hazards in the Chippewa Creek basin. StreamStats regional regression equations were used to estimate instantaneous peak discharges approximately corresponding to bankfull flows. Explanatory variables used in the regression equations were drainage area, main-channel slope, and storage area. Hydraulic models were developed to determine water-surface profiles along the three stream reaches studied for the bankfull discharges established in the hydrologic analyses. The HEC-RAS step-backwater hydraulic analysis model was used to determine water-surface profiles for the three streams. Starting water-surface elevations for all streams were established using normal depth computations in the HEC-RAS models. Cross-sectional elevation data, hydraulic-structure geometries, and roughness coefficients were collected in the field and (along with peak-discharge estimates) used as input for the models. Reach-averaged reductions in water-surface elevations ranged from 0.11 to 1.29 feet over the four roughness coefficient reduction scenarios.

Tumorigenesis of K-ras mutation in human endometrial carcinoma via upregulation of estrogen receptor.

PubMed

Tu, Zheng; Gui, Liming; Wang, Jianliu; Li, Xiaoping; Sun, Pengming; Wei, Lihui

2006-05-01

To investigate the tumorigenesis of mutant [12Asp]-K-ras in endometrial carcinoma and its relationship with ER. We constructed pcDI-[12Asp]K-ras4B by inserting full-length [12Asp]K-ras4B from human endometrial carcinoma Hec-1A cells, into pcDI vector. Cell proliferation of NIH3T3 after transfection with pcDI-[12Asp]K-ras4B was measured by MTT assay. The cell transformation was determined by colony formation and tumor nodule development. [12Asp]-K-ras4B-NIH3T3 cells were transfected with constitutively active pCMV-RafCAAX and dominant-negative pCMV-RafS621A. Cell growth was measured by MTT assay and [3H]thymidine incorporation. After transfected with pcDI-[12Asp]K-ras4B or pCMV-RafS621A, the cells were harvested for Western blot and reporter assay to determine the expression and transcriptional activity of ERalpha and ERbeta, respectively. [12Asp]-K-ras4B enhanced NIH3T3 cells proliferation after 48 h post-transfection (P < 0.05). More colonies were grown 10 days after incubating pcDI-[12Asp]-K-ras4B-NIH3T3 cells (13.48%) than pcDI-NIH3T3 (4.26%) or untreated NIH3T3 (2.33%). The pcDI-[12Asp]-K-ras4B-NIH3T3 cells injected to the nude mice Balb/C developed tumor nodules with poor-differentiated cells after 12 days. An increase of ERalpha and ERbeta was observed in pcDI-[12Asp]-K-ras4B-NIH3T3 cells. RafS621A downregulated ERalpha and ERbeta expression. Estrogen induced the ER transcriptional activity by 5-fold in pcDI-NIH3T3 cells, 13-fold in pcDI-[12Asp]K-ras4B-NIH3T3 and 19-fold in HEC-1A. RafS621A suppressed the ER transcriptional activity. K-ras mutation induces tumorigenesis in endometrium, and this malignant transformation involves Raf signaling pathway and ER.

Developing Sediment Transport and Dredging Prediction Model of Ohio River at Olmsted Locks and Dams Area using HEC-RAS (1D/2D)By Ganesh Raj Ghimire1 and Bruce A. Devantier 2

NASA Astrophysics Data System (ADS)

Ghimire, G. R.

2015-12-01

Sediment deposition is a serious issue in the construction and operation of large reservoir and inland navigation projects in the United States and around the world. Olmsted Locks and Dams in the Ohio River navigation system is facing similar challenges of huge sediment deposition during the ongoing in-wet construction methodology since 1993. HEC-RAS 5.0 integrated with ArcGIS, will be used to yield unsteady 2D hydrodynamic model of Ohio River at Olmsted area. Velocity, suspended sediment, bed sediment and hydrographic survey data acquired from public archives of USGS and USACE Louisville District will be input into the model. Calibration and validation of model will be performed against the measured stage, flow and velocity data. It will be subjected to completely unsteady 1D sediment transport modeling new to HEC-RAS 5.0 which incorporates sediment load and bed gradation via a DSS file, commercial dredging and BSTEM model. Sediment model will be calibrated to replicate the historical bed volume changes. Excavated cross-sections at Olmsted area will also be used to predict the sediment volume trapped inside the ditch over the period between excavations and placement of dam shells at site. Model will attempt to replicate historical dredging volume data and compare with the deposition volume from simulation model to formulate the dredging prediction model. Hence, the results of this research will generate a model that can form a basis for scheduling the dredging event prior to the placement of off-shore cast shells replacing the current as and when required approach of dredging plan. 1 Graduate Student, Department of Civil Engineering, Southern Illinois University Carbondale Carbondale, Illinois, 62901-6603 2 Professor, Department of Civil Engineering, Southern Illinois University Carbondale Carbondale, Illinois, 62901-6603

Flood Study of Warren Brook in Alstead and Cold River in Alstead, Langdon, and Walpole, New Hampshire, 2005

USGS Publications Warehouse

Flynn, Robert H.

2006-01-01

This report presents water-surface elevations and profiles as determined using the U.S. Army Corps of Engineers (USACE) one-dimensional Hydrologic Engineering Center River Analysis System, also known as HEC-RAS. Steady flow water-surface profiles were developed for two stream reaches: the Cold River from its confluence with the Connecticut River in Walpole, through Alstead to the McDermott Bridge in Langdon, NH, and Warren Brook from its confluence with the Cold River to Warren Lake in Alstead, NH. Flood events of a magnitude, which are expected to be equaled or exceeded once on the average during any 10-, 50-, 100-, or 500-year period (recurrence interval), were modeled using HEC-RAS as these flood events are recognized as being significant for flood-plain management, determination of flood insurance rates, and design of structures such as bridges and culverts. These flood events are referred to as the 10-, 50-, 100-, and 500-year floods and have a 10-, 2-, 1-, and 0.2-percent chance, respectively, of being equaled or exceeded during any year. The recurrence intervals represent the long-term average between floods of a specific magnitude. The risk of experiencing rare floods at short intervals or within the same year increases when periods greater than one year are considered. The analyses in this study reflect the flooding potentials based on conditions existing in the communities of Walpole, Alstead and Langdon at the time of completion of this study.

Jackson Bar Training Structure Study

DTIC Science & Technology

2015-05-01

comparison of the one-dimensional bridge hydraulic routines from: HEC - RAS , HEC -2, and WSPRO. Davis, CA: U.S. Army Corps of Engineers, Hydrologic Engineering...ER D C/ CH L TR -1 5- 4 Jackson Bar Training Structure Study Co as ta l a nd H yd ra ul ic s La bo ra to ry Jeremy A. Sharp and...The hydrodynamic model was validated with gage data from the U.S. Geological Survey 02470050 Tombigbee River at Steamplant near Leroy, AL, gage

Rolapitant: A Review in Chemotherapy-Induced Nausea and Vomiting.

PubMed

Heo, Young-A; Deeks, Emma D

2017-10-01

Oral rolapitant (Varubi™; Varuby ® ), a long-acting neurokinin-1 (NK 1 ) receptor antagonist (RA), is indicated in the USA and EU as part of an antiemetic regimen to prevent delayed chemotherapy-induced nausea and vomiting (CINV) in adults receiving highly or moderately emetogenic chemotherapy (HEC or MEC). In randomized, phase III trials, a single oral dose of rolapitant 180 mg was effective in preventing delayed CINV compared with placebo, when each was used in combination with a 5-HT 3 RA plus dexamethasone, in adults receiving their first course of HEC or MEC. The benefits of rolapitant were maintained over multiple cycles of chemotherapy. The tolerability profile of rolapitant is similar to that of placebo and consistent with that of other NK 1 RAs. However, rolapitant differs from other existing NK 1 RAs in that it does not interact with CYP3A4, thereby negating the need for dexamethasone dose adjustments and potentially making rolapitant a more suitable option for patients receiving CYP3A4 substrates. Thus, oral rolapitant is an effective and well tolerated NK 1 RA that expands the treatment options for preventing delayed CINV in adults receiving HEC or MEC.

Developing an Approach to Prioritize River Restoration using Data Extracted from Flood Risk Information System Databases.

NASA Astrophysics Data System (ADS)

Vimal, S.; Tarboton, D. G.; Band, L. E.; Duncan, J. M.; Lovette, J. P.; Corzo, G.; Miles, B.

2015-12-01

Prioritizing river restoration requires information on river geometry. In many states in the US detailed river geometry has been collected for floodplain mapping and is available in Flood Risk Information Systems (FRIS). In particular, North Carolina has, for its 100 Counties, developed a database of numerous HEC-RAS models which are available through its Flood Risk Information System (FRIS). These models that include over 260 variables were developed and updated by numerous contractors. They contain detailed surveyed or LiDAR derived cross-sections and modeled flood extents for different extreme event return periods. In this work, over 4700 HEC-RAS models' data was integrated and upscaled to utilize detailed cross-section information and 100-year modelled flood extent information to enable river restoration prioritization for the entire state of North Carolina. We developed procedures to extract geomorphic properties such as entrenchment ratio, incision ratio, etc. from these models. Entrenchment ratio quantifies the vertical containment of rivers and thereby their vulnerability to flooding and incision ratio quantifies the depth per unit width. A map of entrenchment ratio for the whole state was derived by linking these model results to a geodatabase. A ranking of highly entrenched counties enabling prioritization for flood allowance and mitigation was obtained. The results were shared through HydroShare and web maps developed for their visualization using Google Maps Engine API.

Palonosetron versus older 5-HT3 receptor antagonists for nausea prevention in patients receiving chemotherapy: a multistudy analysis.

PubMed

Morrow, Gary R; Schwartzberg, Lee; Barbour, Sally Y; Ballinari, Gianluca; Thorn, Michael D; Cox, David

2014-07-01

No clinical standard currently exists for the optimal management of nausea induced by emetogenic chemotherapy, 7particularly delayed nausea. To compare the effcacy and safety of palonosetron with older 5-HT3 receptor antagonists (RAs) in preventing chemotherapy-induced nausea. Data were pooled from 4 similarly designed multicenter, randomized, double-blind, clinical trials that compared single intravenous doses of palonosetron 0.25 mg or 0.75 mg with ondansetron 32 mg, dolasetron 100 mg, or granisetron 40 μg/kg, administered 30 minutes before moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC). Pooled data within each chemotherapy category (MEC: n = 1,132; HEC: n = 1,781) were analyzed by a logistic regression model. Nausea endpoints were complete control rates (ie, no more than mild nausea, no vomiting, and no rescue medication), nausea-free rates, nausea severity, and requirement for rescue antiemetic/antinausea medication over 5 days following chemotherapy. Pooled safety data were summarized descriptively. Numerically more palonosetron-treated patients were nausea-free on each day, and fewer had moderate-severe nausea. Similarly, usage of rescue medication was less frequent among palonosetron-treated patients. Complete control rates for palonosetron and older 5-HT3 RAs in the acute phase were 66% vs 63%, 52% vs 42% in the delayed phase (24-120 hours), and 46% vs 37% in the overall phase. The incidence of adverse events was similar for palonosetron and older 5-HT3 RAs. This post hoc analysis summarized data for palonosetron and several other 5-HT3 RAs but was not powered for statistical comparisons between individual agents. Because nausea is inherently subjective, the reliability of assessments of some aspects (eg, severity) may be infuenced by interindividual variability. Palonosetron may be more effective than older 5-HT3 RAs in preventing nausea, with comparable tolerability. Dr Schwartzberg is a consultant to and Dr Cox an employee at Esai. Mr Ballinari is a member of staff at and Dr Thorn consults for Helsinn Healthcare SA. Funding to support this study and the preparation of this manuscript was provided by Eisai Inc. 2014 FrontlineMedical Communications.

[Aromatase activities of endometrial carcinomas and both basic and clinical analyses of endometrial hyperplasia as a premalignant disease].

PubMed

Sasaki, H

1993-08-01

Paraffin-embedded materials obtained from 117 cases of endometrial hyperplasia and 84 cases of carcinoma were used for measurement of both ki-ras and p53 gene mutation and aromatase (ARO) and TGF-alpha immunostaining. The overall incidence of ki-ras mutations in the hyperplasia specimens (16%) was similar to the incidence detected in carcinomas (18%). None of 117 endometrial hyperplasias were found to have mutations in the p53 gene, whereas mutations were seen in 3 (13.3%) endometrial carcinomas. The intensity of both ARO and TGF-alpha immunostaining was increased in glands of both hyperplasia and carcinoma, and also in the interstitium of carcinoma. The positive sites of both ARO and TGF-alpha were almost the same, with an incidence below 40% in both hyperplasias and carcinomas. The cultured cells of endometrial carcinoma showed aromatase activity below MCF-7 cells, because testosterone was converted to estradiol (E2). TGF-alpha induced cell growth with at an optimal concentration. In HEC-59 cells, TGF-alpha increased both ARO-activity and mRNA. Some promoters on ARO-exon 1 in HEC-59 cells were different from those in BeWo cells. Progesterone inhibited the E2-induced excretion of pre TGF-alpha in endometrial carcinoma cells. These findings suggest that endometrial hyperplasia can be a premalignant condition of carcinoma, and can be initiated by both ki-ras codon 12 mutation and abnormal activity of ARO induced by TGF-alpha. In addition, HEC-59 cells may possess autocrine/paracrine properties involving ARO, E2 and TGF-alpha.

[The factors involved in invasive ability of endometrial carcinoma cells].

PubMed

Mori, Y; Mizuuchi, H; Sato, K; Okamura, N; Kudo, R

1994-06-01

The in vitro invasive ability, the expression of cell adhesion molecule E-cadherin, activity of matrix metalloproteinase (MMP) and K-ras point mutation were investigated in eight human endometrial carcinoma cell lines. 1) In vitro invasive abilities of endometrial carcinoma cell lines depend on the degree of cell differentiation and the origin of cell lines. A poorly-differentiated carcinoma cell line (NUE-1) and a cell line derived from metastatic lymph node (SNG-M) were more invasive than moderately-(HEC-1A, HEC-1BE) and well-differentiated (HEC-6, Ishikawa) cell lines. 2) Immunohistochemically, less or non-invasive cell lines expressed E-cadherin strongly, whereas a highly invasive cell line (NUE-1) expressed E-cadherin weakly. 3) When cultured on Matrigel-coated dishes, the tumor cells derived from moderately- and well-differentiated carcinoma aggregated with each other and did not invade Matrigel in the invasion assay. The aggregated cells expressed E-cadherin more strongly when cultured on Matrigel. 4) 72-kD gelatinase (MMP-2) was secreted in serum-free conditioned medium of all cell lines. In an invasive cell line (NUE-1,SNG-M), the activity of MMP-2 was stronger than in other cell lines. And the activity of 92-kDa gelatinase (MMP-9) was detected in most invasive cell line (NUE-1). 5) Point mutation of K-ras codon 12 was detected in four of eight (50%) cell lines by the PCR-RFLP method. The changes in the DNA sequence were identified, but K-ras point mutation was not correlated with in vitro invasiveness of the tumor cells.

Comparison of physical and semi-empirical hydraulic models for flood inundation mapping

NASA Astrophysics Data System (ADS)

Tavakoly, A. A.; Afshari, S.; Omranian, E.; Feng, D.; Rajib, A.; Snow, A.; Cohen, S.; Merwade, V.; Fekete, B. M.; Sharif, H. O.; Beighley, E.

2016-12-01

Various hydraulic/GIS-based tools can be used for illustrating spatial extent of flooding for first-responders, policy makers and the general public. The objective of this study is to compare four flood inundation modeling tools: HEC-RAS-2D, Gridded Surface Subsurface Hydrologic Analysis (GSSHA), AutoRoute and Height Above the Nearest Drainage (HAND). There is a trade-off among accuracy, workability and computational demand in detailed, physics-based flood inundation models (e.g. HEC-RAS-2D and GSSHA) in contrast with semi-empirical, topography-based, computationally less expensive approaches (e.g. AutoRoute and HAND). The motivation for this study is to evaluate this trade-off and offer guidance to potential large-scale application in an operational prediction system. The models were assessed and contrasted via comparability analysis (e.g. overlapping statistics) by using three case studies in the states of Alabama, Texas, and West Virginia. The sensitivity and accuracy of physical and semi-eimpirical models in producing inundation extent were evaluated for the following attributes: geophysical characteristics (e.g. high topographic variability vs. flat natural terrain, urbanized vs. rural zones, effect of surface roughness paratermer value), influence of hydraulic structures such as dams and levees compared to unobstructed flow condition, accuracy in large vs. small study domain, effect of spatial resolution in topographic data (e.g. 10m National Elevation Dataset vs. 0.3m LiDAR). Preliminary results suggest that semi-empericial models tend to underestimate in a flat, urbanized area with controlled/managed river channel around 40% of the inundation extent compared to the physical models, regardless of topographic resolution. However, in places where there are topographic undulations, semi-empericial models attain relatively higher level of accuracy than they do in flat non-urbanized terrain.

Modeling Alpine Meadow Restoration Techniques and their Effects on Stream Stage Regimes

NASA Astrophysics Data System (ADS)

Moore, C. E.; Lundquist, J. D.; Loheide, S. P.

2010-12-01

Meadow ecosystems in the Sierra Nevada of California often suffer from negative anthropogenic impacts, resulting in stream incision and meadow aridification. Groundwater dependent ecosystems, such as meadows, are especially vulnerable to channel degradation because alteration of stream stage propagates through the groundwater system to affect riparian vegetation. Restoration aimed at raising water table elevation of degraded meadow systems is becoming a salient and viable option as managers recognize the importance of intact headwaters. Stream stage controls groundwater levels and thus, vegetation communities, more dramatically than stream discharge in groundwater dependent ecosystems. Here we use a one dimensional hydraulic model, Hydraulic Engineering Center - River Analysis System (HEC-RAS) to model stream stage along the Tuolumne River, given a time series of stream discharge. Extensive hydroclimatic monitoring since 2001, and groundwater monitoring since 2006, make Tuolumne Meadows, in Yosemite National Park, California a prime location for a validated case study, applicable to other snow dominated basins. In order to determine the most plausible, efficient and effective strategy of restoring impacted meadows, different management scenarios are modeled. HEC-RAS modeling provides critical stream stage boundary conditions for groundwater modeling. Scenarios are chosen that are most effective at increasing stream stage and therefore water table levels. The effectiveness is quantified by modeling how each scenario changes the rating curve for a particular channel. Additionally, surface stage modeling allows decision makers to see under what flow conditions and what time period of the hydrograph is affected by restoration. Quantification of stream stage alterations is key for understanding restoration impacts during the short growing season in alpine meadows. Results of HEC-RAS modeling at Tuolumne Meadows are presented in the following formats to highlight the ways in which this work can be used as a vital tool in management decisions regarding meadow restoration. First, direct changes to the resulting stream stage time series are used to illustrate the magnitude of change among scenarios. Second, synthetic rating curves are compared so that the flow regimes which are highly sensitive to a particular restoration strategy can be readily identified. Third, an empirical probability density function describing the stream stage regime will be provided for each scenario to illustrate the overall effectiveness of each restoration technique in changing water levels. Finally, the probability of exceedance for bankfull stage, the depth associated with the onset of oxygen stress, and the depth associated with the onset of water stress will be presented to demonstrate changes to stream levels that are believed to have ecological significance. Investigation of multiple scenarios allows an informed decision based on sound science that will help achieve restoration goals in the future.

Genotyping of K-ras codons 12 and 13 mutations in colorectal cancer by capillary electrophoresis.

PubMed

Chen, Yen-Ling; Chang, Ya-Sian; Chang, Jan-Gowth; Wu, Shou-Mei

2009-06-26

Point mutations of the K-ras gene located in codons 12 and 13 cause poor responses to the anti-epidermal growth factor receptor (anti-EGFR) therapy of colorectal cancer (CRC) patients. Besides, mutations of K-ras gene have also been proven to play an important role in human tumor progression. We established a simple and effective capillary electrophoresis (CE) method for simultaneous point mutation detection in codons 12 and 13 of K-ras gene. We combined one universal fluorescence-based nonhuman-sequence primer and two fragment-oriented primers in one tube, and performed this two-in-one polymerase chain reaction (PCR). PCR fragments included wild type and seven point mutations at codons 12 and 13 of K-ras gene. The amplicons were analyzed by single-strand conformation polymorphism (SSCP)-CE method. The CE analysis was performed by using a 1x Tris-borate-EDTA (TBE) buffer containing 1.5% (w/v) hydroxyethylcellulose (HEC) (MW 250,000) under reverse polarity with 15 degrees C and 30 degrees C. Ninety colorectal cancer patients were blindly genotyped using this developed method. The results showed good agreement with those of DNA sequencing method. The SSCP-CE was feasible for mutation screening of K-ras gene in populations.

Flood Prediction for the Tam Nong District in Mekong Delta Using Hydrological Modelling and Hydrologic Remote Sensing Technique

NASA Astrophysics Data System (ADS)

Kappas, Martin; Nguyen Hong, Quang; Thanh, Nga Pham Thi; Thu, Hang Le Thi; Nguyen Vu, Giang; Degener, Jan; Rafiei Emam, Ammar

2017-04-01

There has been an increasing attention to the large trans-boundary Mekong river basin due to various problems related to water management and flood control, for instance. Vietnam Mekong delta is located at the downstream of the river basin where is affected most by this human-induced reduction in flows from the upstream. On the other hand, the flood plain of nine anastomosing channels is increasingly effected by the seawater intrusion due to sea level rising of climate change. This results in negative impacts of salinization, drought, and floods, while formerly flooding had frequently brought positive natural gain of irrigation water and alluvial aggradation. In this research, our aim is to predict flooding for the better water management adaptation and control. We applied the model HEC-SSP 2.1 to analyze flood flow frequency, two-dimensional unsteady flow calculations in HEC-RAS 5.0 for simulating a floodplain inundation. Remote sensing-based water level (Jason-2) and inundation map were used for validation and comparison with the model simulations. The results revealed a reduction of water level at all the monitoring stations, particularly in the last decade. In addition, a trend of the inundation extension gradually declined, but in some periods it remained severe due to water release from upstream reservoirs during the rainy season (October-November). We found an acceptable agreement between the HEC-RAS and remote sensing flooding maps (around 70%). Based on the flood routine analysis, we could conclude that the water level will continue lower and lead to a trend of drought and salinization harsher in the near future. Keywords: Mekong delta, flood control, inundation, water management, hydrological modelling, remote sensing

Corps Water Management System (CWMS) Decision Support Modeling and Integration Use in the June 2007 Texas Floods

NASA Astrophysics Data System (ADS)

Charley, W. J.; Luna, M.

2007-12-01

The U.S. Army Corps of Engineers Corps Water Management System (CWMS) is a comprehensive data acquisition and hydrologic modeling system for short-term decision support of water control operations in real time. It encompasses data collection, validation and transformation, data storage, visualization, real time model simulation for decision-making support, and data dissemination. CWMS uses an Oracle database and Sun Solaris workstations for data processes, storage and the execution of models, with a client application (the Control and Visualization Interface, or CAVI) that can run on a Windows PC. CWMS was used by the Lower Colorado River Authority (LCRA) to make hydrologic forecasts of flows on the Lower Colorado River and operate reservoirs during the June 2007 event in Texas. The LCRA receives real-time observed gridded spatial rainfall data from OneRain, Inc. that which is a result of adjusting NexRad rainfall data with precipitation gages. This data is used, along with future precipitation estimates, for hydrologic forecasting by the rainfall-runoff modeling program HEC-HMS. Forecasted flows from HEC-HMS and combined with observed flows and reservoir information to simulate LCRA's reservoir operations and help engineers make release decisions based on the results. The river hydraulics program, HEC-RAS, computes river stages and water surface profiles for the computed flow. An inundation boundary and depth map of water in the flood plain can be calculated from the HEC-RAS results using ArcInfo. By varying future precipitation and releases, engineers can evaluate different "What if?" scenarios. What was described as an "extraordinary cluster of thunderstorms" that stalled over Burnet and Llano counties in Texas on June 27, 2007, dropped 17 to 19 inches of rainfall over a 6-hour period. The storm was classified over a 500-year event and the resulting flow over some of the smaller tributaries as a 100-year or better. CWMS was used by LCRA for flood forecasting and reservoir operations. The models accurately forecasting the flows and allowed engineers to determine that only four floodgates needed to be opened for Mansfield dam, in the Chain of Highland lakes. CWMS also forecasted the peak of the flood well before it happened. Smaller rain storms continued for a period of weeks and CWMS was used throughout the event calculating lake levels, closing of gates along with a hydro-generation schedule.

Error of the modelled peak flow of the hydraulically reconstructed 1907 flood of the Ebro River in Xerta (NE Iberian Peninsula)

NASA Astrophysics Data System (ADS)

Lluís Ruiz-Bellet, Josep; Castelltort, Xavier; Carles Balasch, J.; Tuset, Jordi

2016-04-01

The estimation of the uncertainty of the results of the hydraulic modelling has been deeply analysed, but no clear methodological procedures as to its determination have been formulated when applied to historical hydrology. The main objective of this study was to calculate the uncertainty of the resulting peak flow of a typical historical flood reconstruction. The secondary objective was to identify the input variables that influenced the result the most and their contribution to peak flow total error. The uncertainty of 21-23 October 1907 flood of the Ebro River (NE Iberian Peninsula) in the town of Xerta (83,000 km2) was calculated with a series of local sensitivity analyses of the main variables affecting the resulting peak flow. Besides, in order to see to what degree the result depended on the chosen model, the HEC-RAS resulting peak flow was compared to the ones obtained with the 2D model Iber and with Manning's equation. The peak flow of 1907 flood in the Ebro River in Xerta, reconstructed with HEC-RAS, was 11500 m3·s-1 and its total error was ±31%. The most influential input variable over HEC-RAS peak flow results was water height; however, the one that contributed the most to peak flow error was Manning's n, because its uncertainty was far greater than water height's. The main conclusion is that, to ensure the lowest peak flow error, the reliability and precision of the flood mark should be thoroughly assessed. The peak flow was 12000 m3·s-1 when calculated with the 2D model Iber and 11500 m3·s-1 when calculated with the Manning equation.

Digital Elevation Model Correction for the thalweg values of Obion River system, TN

NASA Astrophysics Data System (ADS)

Dullo, T. T.; Bhuyian, M. N. M.; Hawkins, S. A.; Kalyanapu, A. J.

2016-12-01

Obion River system is located in North-West Tennessee and discharges into the Mississippi River. To facilitate US Department of Agriculture (USDA) to estimate water availability for agricultural consumption a one-dimensional HEC-RAS model has been proposed. The model incorporates the major tributaries (north and south), main stem of Obion River along with a segment of the Mississippi River. A one-meter spatial resolution Light Detection and Ranging (LiDAR) derived Digital Elevation Model (DEM) was used as the primary source of topographic data. LiDAR provides fine-resolution terrain data over given extent. However, it lacks in accurate representation of river bathymetry due to limited penetration beyond a certain water depth. This reduces the conveyance along river channel as represented by the DEM and affects the hydrodynamic modeling performance. This research focused on proposing a method to overcome this issue and test the qualitative improvement by the proposed method over an existing technique. Therefore, objective of this research is to compare effectiveness of a HEC-RAS based bathymetry optimization method with an existing hydraulic based DEM correction technique (Bhuyian et al., 2014) for Obion River system in Tennessee. Accuracy of hydrodynamic simulations (upon employing bathymetry from respective sources) would be regarded as the indicator of performance. The aforementioned river system includes nine major reaches with a total river length of 310 km. The bathymetry of the river was represented via 315 cross sections equally spaced at about one km. This study targeted to selecting best practice for treating LiDAR based terrain data over complex river system at a sub-watershed scale.

The impact of 5-hydroxytryptamine-receptor antagonists on chemotherapy treatment adherence, treatment delay, and nausea and vomiting.

PubMed

Palli, Swetha Rao; Grabner, Michael; Quimbo, Ralph A; Rugo, Hope S

2015-01-01

To determine the incidence of chemotherapy-induced nausea/vomiting (CINV) and chemotherapy treatment delay and adherence among patients receiving palonosetron versus other 5-hydroxytryptamine receptor antagonist (5-HT3 RA) antiemetics. This retrospective claims analysis included adults with primary malignancies who initiated treatment consisting of single-day intravenous highly emetogenic chemotherapy (HEC) or moderately EC (MEC) regimens. Treatment delay was defined as a gap in treatment at least twice the National Comprehensive Cancer Network-specified cycle length, specific to each chemotherapy regimen. Treatment adherence was determined by the percentage of patients who received the regimen-specific recommended number of chemotherapy cycles within the recommended time frame. We identified 1,832 palonosetron and 2,387 other 5-HT3 RA ("other") patients who initiated HEC therapy, and 1,350 palonosetron users and 1,379 patients on other antiemetics who initiated MEC therapy. Fewer patients receiving palonosetron experienced CINV versus other (HEC, 27.5% versus 32.2%, P=0.0011; MEC, 36.1% versus 41.7%, P=0.0026), and fewer treatment delays occurred among patients receiving palonosetron versus other (HEC, 3.2% versus 6.0%, P<0.0001; MEC, 17.0% versus 26.8%, P<0.0001). Compared with the other cohort, patients receiving palonosetron were significantly more adherent to the index chemotherapy regimen with respect to the recommended time frame (HEC, 74.7% versus 69.7%, P=0.0004; MEC, 43.1% versus 37.3%, P=0.0019) and dosage (HEC, 27.3% versus 25.8%, P=0.0004; MEC, 15.0% versus 12.6%, P=0.0019). Palonosetron more effectively reduced occurrence of CINV in patients receiving HEC or MEC compared with other agents in this real-world setting. Additionally, patients receiving palonosetron had better adherence and fewer treatment delays than patients receiving other 5-HT3 RAs.

The impact of 5-hydroxytryptamine-receptor antagonists on chemotherapy treatment adherence, treatment delay, and nausea and vomiting

PubMed Central

Palli, Swetha Rao; Grabner, Michael; Quimbo, Ralph A; Rugo, Hope S

2015-01-01

Purpose To determine the incidence of chemotherapy-induced nausea/vomiting (CINV) and chemotherapy treatment delay and adherence among patients receiving palonosetron versus other 5-hydroxytryptamine receptor antagonist (5-HT3 RA) antiemetics. Materials and methods This retrospective claims analysis included adults with primary malignancies who initiated treatment consisting of single-day intravenous highly emetogenic chemotherapy (HEC) or moderately EC (MEC) regimens. Treatment delay was defined as a gap in treatment at least twice the National Comprehensive Cancer Network-specified cycle length, specific to each chemotherapy regimen. Treatment adherence was determined by the percentage of patients who received the regimen-specific recommended number of chemotherapy cycles within the recommended time frame. Results We identified 1,832 palonosetron and 2,387 other 5-HT3 RA (“other”) patients who initiated HEC therapy, and 1,350 palonosetron users and 1,379 patients on other antiemetics who initiated MEC therapy. Fewer patients receiving palonosetron experienced CINV versus other (HEC, 27.5% versus 32.2%, P=0.0011; MEC, 36.1% versus 41.7%, P=0.0026), and fewer treatment delays occurred among patients receiving palonosetron versus other (HEC, 3.2% versus 6.0%, P<0.0001; MEC, 17.0% versus 26.8%, P<0.0001). Compared with the other cohort, patients receiving palonosetron were significantly more adherent to the index chemotherapy regimen with respect to the recommended time frame (HEC, 74.7% versus 69.7%, P=0.0004; MEC, 43.1% versus 37.3%, P=0.0019) and dosage (HEC, 27.3% versus 25.8%, P=0.0004; MEC, 15.0% versus 12.6%, P=0.0019). Conclusion Palonosetron more effectively reduced occurrence of CINV in patients receiving HEC or MEC compared with other agents in this real-world setting. Additionally, patients receiving palonosetron had better adherence and fewer treatment delays than patients receiving other 5-HT3 RAs. PMID:26124681

Assessment Approach for Identifying Compatibility of Restoration Projects with Geomorphic and Flooding Processes in Gravel Bed Rivers

NASA Astrophysics Data System (ADS)

DeVries, Paul; Aldrich, Robert

2015-08-01

A critical requirement for a successful river restoration project in a dynamic gravel bed river is that it be compatible with natural hydraulic and sediment transport processes operating at the reach scale. The potential for failure is greater at locations where the influence of natural processes is inconsistent with intended project function and performance. We present an approach using practical GIS, hydrologic, hydraulic, and sediment transport analyses to identify locations where specific restoration project types have the greatest likelihood of working as intended because their function and design are matched with flooding and morphologic processes. The key premise is to identify whether a specific river analysis segment (length ~1-10 bankfull widths) within a longer reach is geomorphically active or inactive in the context of vertical and lateral stabilities, and hydrologically active for floodplain connectivity. Analyses involve empirical channel geometry relations, aerial photographic time series, LiDAR data, HEC-RAS hydraulic modeling, and a time-integrated sediment transport budget to evaluate trapping efficiency within each segment. The analysis segments are defined by HEC-RAS model cross sections. The results have been used effectively to identify feasible projects in a variety of alluvial gravel bed river reaches with lengths between 11 and 80 km and 2-year flood magnitudes between ~350 and 1330 m3/s. Projects constructed based on the results have all performed as planned. In addition, the results provide key criteria for formulating erosion and flood management plans.

Assessment Approach for Identifying Compatibility of Restoration Projects with Geomorphic and Flooding Processes in Gravel Bed Rivers.

PubMed

DeVries, Paul; Aldrich, Robert

2015-08-01

A critical requirement for a successful river restoration project in a dynamic gravel bed river is that it be compatible with natural hydraulic and sediment transport processes operating at the reach scale. The potential for failure is greater at locations where the influence of natural processes is inconsistent with intended project function and performance. We present an approach using practical GIS, hydrologic, hydraulic, and sediment transport analyses to identify locations where specific restoration project types have the greatest likelihood of working as intended because their function and design are matched with flooding and morphologic processes. The key premise is to identify whether a specific river analysis segment (length ~1-10 bankfull widths) within a longer reach is geomorphically active or inactive in the context of vertical and lateral stabilities, and hydrologically active for floodplain connectivity. Analyses involve empirical channel geometry relations, aerial photographic time series, LiDAR data, HEC-RAS hydraulic modeling, and a time-integrated sediment transport budget to evaluate trapping efficiency within each segment. The analysis segments are defined by HEC-RAS model cross sections. The results have been used effectively to identify feasible projects in a variety of alluvial gravel bed river reaches with lengths between 11 and 80 km and 2-year flood magnitudes between ~350 and 1330 m(3)/s. Projects constructed based on the results have all performed as planned. In addition, the results provide key criteria for formulating erosion and flood management plans.

"Flooding Risk Analysis and the Understanding of Hydrological Disturbance due to the Rapid Urbanization in a Low-Scale Subwatershed in Houston Area". ( The project develops a relavant Model of flooding risk assessment to define the connection between increased streamflow/flooding and the rapid urban land development).

NASA Astrophysics Data System (ADS)

Geldiyev, P.

2017-12-01

Rapid urban development and changing climate influences the frequency and magnitude of flooding in Houston area. This proposed project aims to evaluate the flooding risks with the current and future land use changes by 2040 for one subbasin of the San Jacinto Brazos/Neches-Trinity Coastal basin. Surface environments and streamflow data of the Clear Creek are analyzed and stimulated to discuss the possible impact of urbanization on the occurrence of floods. The streamflow data is analyzed and simulated with the application of the Geographic Information Systems and its extensions. Both hydrologic and hydraulic models of the Clear Creek are created with the use of HEC-HMS and HEC-RAS software. Both models are duplicated for the year 2040, based on projected 2040 Landcover Maps developed by Houston and Galveston Area Council. This project examines a type of contemporary hydrologic disturbance and the interaction between land cover and changes in hydrological processes. Expected results will be very significant for urban development and flooding management.

Combined Hydrologic (AGWA-KINEROS2) and Hydraulic (HEC2) Modeling for Post-Fire Runoff and Inundation Risk Assessment through a Set of Python Tools

NASA Astrophysics Data System (ADS)

Barlow, J. E.; Goodrich, D. C.; Guertin, D. P.; Burns, I. S.

2016-12-01

Wildfires in the Western United States can alter landscapes by removing vegetation and changing soil properties. These altered landscapes produce more runoff than pre-fire landscapes which can lead to post-fire flooding that can damage infrastructure and impair natural resources. Resources, structures, historical artifacts and others that could be impacted by increased runoff are considered values at risk. .The Automated Geospatial Watershed Assessment tool (AGWA) allows users to quickly set up and execute the Kinematic Runoff and Erosion model (KINEROS2 or K2) in the ESRI ArcMap environment. The AGWA-K2 workflow leverages the visualization capabilities of GIS to facilitate evaluation of rapid watershed assessments for post-fire planning efforts. High relative change in peak discharge, as simulated by K2, provides a visual and numeric indicator to investigate those channels in the watershed that should be evaluated for more detailed analysis, especially if values at risk are within or near that channel. Modeling inundation extent along a channel would provide more specific guidance about risk along a channel. HEC-2 and HEC-RAS can be used for hydraulic modeling efforts at the reach and river system scale. These models have been used to address flood boundaries and, accordingly, flood risk. However, data collection and organization for hydraulic models can be time consuming and therefore a combined hydrologic-hydraulic modeling approach is not often employed for rapid assessments. A simplified approach could streamline this process and provide managers with a simple workflow and tool to perform a quick risk assessment for a single reach. By focusing on a single reach highlighted by large relative change in peak discharge, data collection efforts can be minimized and the hydraulic computations can be performed to supplement risk analysis. The incorporation of hydraulic analysis through a suite of Python tools (as outlined by HEC-2) with AGWA-K2 will allow more rapid applications of combined hydrologic-hydraulic modeling. This combined modeling approach is built in the ESRI ArcGIS application to enable rapid model preparation, execution and result visualization for risk assessment in post-fire environments.

New Techniques for Real-Time Stage Forecasting for Tributaries in the Nashville Area

NASA Astrophysics Data System (ADS)

Charley, W.; Moran, B.; LaRosa, J.

2011-12-01

On Saturday, May 1, 2010, heavy rain began falling in the Cumberland River Valley, Tennessee, and continued through the following day. 13.5 inches was measured at Nashville, an unprecedented amount that doubled the previous 2-day record, and exceeded the May monthly total record of 11 inches. Elsewhere in the valley, amounts of over 19 inches were measured. This intensity of rainfall quickly overwhelmed tributaries to the Cumberland in the Nashville area, causing wide-spread and serious flooding. Tractor-trailers and houses were seen floating down Mill Creek, a primary tributary in the south eastern area of Nashville. Twenty-six people died and over 2 billion dollars in damage occurred as a result of the flood. Since that time, several other significant rainfall events have occurred in the area. As a result of the flood, agencies in the Nashville area want better capabilities to forecast stages for the local tributaries. Better stage forecasting will help local agencies close roads, evacuate homes and businesses and similar actions. An interagency group, consisting of Metro Nashville Water Services and Office of Emergency Management, the National Weather Service, the US Geological Survey and the US Army Corps of Engineers, has been established to seek ways to better forecast short-term events in the region. It should be noted that the National Weather Service has the official responsibility of forecasting stages. This paper examines techniques and algorithms that are being developed to meet this need and the practical aspects of integrating them into a usable product that can quickly and accurately forecast stages in the short-time frame of the tributaries. This includes not only the forecasting procedure, but also the procedure to acquire the latest precipitation and stage data to make the forecasts. These procedures are integrated into the program HEC-RTS, the US Army Corps of Engineers Real-Time Simulation program. HEC-RTS is a Java-based integration tool that has been derived from the Corps Water Management System (CWMS). The modeling component takes observed and forecasted rainfall to compute river flow with the program HEC-HMS. The river hydraulics program, HEC-RAS, computes river stages and water surface profiles. An inundation boundary and depth map of water in the flood plain is computed from HEC-RAS Mapper. The user-configurable sequence of modeling software allows engineers to evaluate and compare hydraulic impacts for various "what if?" scenarios. The implementation of these techniques and HEC-RTS is examined for the Mill Creek basin, the 108 square mile tributary basin south east of Nashville. Mill Creek has an average annual flow of 150 CFS and a short response time. It has suffered major damage from the 2010 and other events. The accuracy and effectiveness of the techniques in the integrated tool HEC-RTS is evaluated.

Application of the FluEgg model to predict transport of Asian carp eggs in the Saint Joseph River (Great Lakes tributary)

USGS Publications Warehouse

Garcia, Tatiana; Murphy, Elizabeth A.; Jackson, P. Ryan; Garcia, Marcelo H.

2015-01-01

The Fluvial Egg Drift Simulator (FluEgg) is a three-dimensional Lagrangian model that simulates the movement and development of Asian carp eggs until hatching based on the physical characteristics of the flow field and the physical and biological characteristics of the eggs. This tool provides information concerning egg development and spawning habitat suitability including: egg plume location, egg vertical and travel time distribution, and egg-hatching risk. A case study of the simulation of Asian carp eggs in the Lower Saint Joseph River, a tributary of Lake Michigan, is presented. The river hydrodynamic input for FluEgg was generated in two ways — using hydroacoustic data and using HEC-RAS model data. The HEC-RAS model hydrodynamic input data were used to simulate 52 scenarios covering a broad range of flows and water temperatures with the eggs at risk of hatching ranging from 0 to 93% depending on river conditions. FluEgg simulations depict the highest percentage of eggs at risk of hatching occurs at the lowest discharge and at peak water temperatures. Analysis of these scenarios illustrates how the interactive relation among river length, hydrodynamics, and water temperature influence egg transport and hatching risk. An improved version of FluEgg, which more realistically simulates dispersion and egg development, is presented. Also presented is a graphical user interface that facilitates the use of FluEgg and provides a set of post-processing analysis tools to support management decision-making regarding the prevention and control of Asian carp reproduction in rivers with or without Asian carp populations.

Sedimentation Impacts Modeling for the Lower Elwha River

NASA Astrophysics Data System (ADS)

Beggs, M.; Kosaka, M.; Sigel, A.; Vandermause, R.; Lauer, J. W.

2012-12-01

The removal of Glines Canyon and Elwha Dams from the Elwha River, northwest Washington, is intended to restore natural geomorphic and ecological processes to the Elwha River basin. Prior to the start of dam removal, over 16 million cubic meters of sediment had accumulated in the reservoirs above the two dams. As dam removal progresses, a portion of this sediment will erode and then be deposited on the downstream river bed and floodplain. To address uncertainty in downstream response to the project, the United States Bureau of Reclamation is implementing an adaptive management plan that relies upon continuous monitoring of water levels at a set of stream gages along the river. To interpret the monitoring data and allow for rapid assessment of the rate of downstream sedimentation, we developed rating curves at several locations along the lower Elwha River. The curves consider a range of possible sedimentation scenarios, each involving different sedimentation levels and/or locations. One scenario considers sedimentation primarily in the river channel, another considers sedimentation primarily on the floodplain, and a third considers both possibilities in tandem. We modeled these scenarios using two separate approaches. First, we modified the cross sections in an existing U.S. Army Corps of Engineers HEC-RAS model to represent possible changes associated with geomorphic adjustment to the dam removals. In-channel sedimentation was assumed to occur as a constant fraction of the bankfull depth at any given section, thereby focusing geomorphic change in relatively deep pool areas. In the HEC-RAS model, off-channel sedimentation was assumed uniform. The HEC-RAS model showed that both low-flow and flood hydraulics are much more sensitive to plausible levels of in-channel sedimentation than to plausible levels of overbank sedimentation. The wide floodplain, complex secondary channels, and geomorphic evolution since the original cross sections were surveyed raise some questions regarding the validity of our 1-D HEC-RAS results and motivated our second approach, which involved developing an independent 2-D hydraulic model using the U.S. Bureau of Reclamation SRH-2d program. This model had the added benefit of being able to utilize more recently surveyed bathymetric and topographic data. The 2-D model was used to improve the representation of spatial variability of likely floodplain sedimentation. For this, we used a preliminary run of the program to characterize the water surface elevation for a typical flood event. We then used the modeled water surface as an input for an eight direction pour point determination of flow direction in ArcGIS. This allowed us to approximate the flow distance from the main channel along streamlines crossing the floodplain. Using observed levee morphology, we developed an ad-hoc exponential function for overbank sedimentation as a function of flow distance from the channel. This tended to focus deposition on natural levees at the upstream side of point bars or meander necks. Despite the more narrowly focused zone of floodplain sedimentation, however, the results were consistent with the 1-D result that in-channel sedimentation is like to have a greater relative impact on system-wide hydraulics than does overbank sedimentation.

Numerical Limitations of 1D Hydraulic Models Using MIKE11 or HEC-RAS software - Case study of Baraolt River, Romania

NASA Astrophysics Data System (ADS)

Andrei, Armas; Robert, Beilicci; Erika, Beilicci

2017-10-01

MIKE 11 is an advanced hydroinformatic tool, a professional engineering software package for simulation of one-dimensional flows in estuaries, rivers, irrigation systems, channels and other water bodies. MIKE 11 is a 1-dimensional river model. It was developed by DHI Water · Environment · Health, Denmark. The basic computational procedure of HEC-RAS for steady flow is based on the solution of the one-dimensional energy equation. Energy losses are evaluated by friction and contraction / expansion. The momentum equation may be used in situations where the water surface profile is rapidly varied. These situations include hydraulic jumps, hydraulics of bridges, and evaluating profiles at river confluences. For unsteady flow, HEC-RAS solves the full, dynamic, 1-D Saint Venant Equation using an implicit, finite difference method. The unsteady flow equation solver was adapted from Dr. Robert L. Barkau’s UNET package. Fluid motion is controlled by the basic principles of conservation of mass, energy and momentum, which form the basis of fluid mechanics and hydraulic engineering. Complex flow situations must be solved using empirical approximations and numerical models, which are based on derivations of the basic principles (backwater equation, Navier-Stokes equation etc.). All numerical models are required to make some form of approximation to solve these principles, and consequently all have their limitations. The study of hydraulics and fluid mechanics is founded on the three basic principles of conservation of mass, energy and momentum. Real-life situations are frequently too complex to solve without the aid of numerical models. There is a tendency among some engineers to discard the basic principles taught at university and blindly assume that the results produced by the model are correct. Regardless of the complexity of models and despite the claims of their developers, all numerical models are required to make approximations. These may be related to geometric limitations, numerical simplification, or the use of empirical correlations. Some are obvious: one-dimensional models must average properties over the two remaining directions. It is the less obvious and poorly advertised approximations that pose the greatest threat to the novice user. Some of these, such as the inability of one-dimensional unsteady models to simulate supercritical flow can cause significant inaccuracy in the model predictions.

The Impact of Corps Flood Control Reservoirs in the June 2008 Upper Mississippi Flood

NASA Astrophysics Data System (ADS)

Charley, W. J.; Stiman, J. A.

2008-12-01

The US Army Corps of Engineers is responsible for a multitude of flood control project on the Mississippi River and its tributaries, including levees that protect land from flooding, and dams to help regulate river flows. The first six months of 2008 were the wettest on record in the upper Mississippi Basin. During the first 2 weeks of June, rainfall over the Midwest ranged from 6 to as much as 16 inches, overwhelming the flood protection system, causing massive flooding and damage. Most severely impacted were the States of Iowa, Illinois, Indiana, Missouri, and Wisconsin. In Iowa, flooding occurred on almost every river in the state. On the Iowa River, record flooding occurred from Marshalltown, Iowa, downstream to its confluence with the Mississippi River. At several locations, flooding exceeded the 500-year event. The flooding affected agriculture, transportation, and infrastructure, including homes, businesses, levees, and other water-control structures. It has been estimated that there was at least 7 billion dollars in damages. While the flooding in Iowa was extraordinary, Corps of Engineers flood control reservoirs helped limit damage and prevent loss of life, even though some reservoirs were filled beyond their design capacity. Coralville Reservoir on the Iowa River, for example, filled to 135% of its design flood storage capacity, with stage a record five feet over the crest of the spillway. In spite of this, the maximum reservoir release was limited to 39,500 cfs, while a peak inflow of 57,000 cfs was observed. CWMS, the Corps Water Management System, is used to help regulate Corps reservoirs, as well as track and evaluate flooding and flooding potential. CWMS is a comprehensive data acquisition and hydrologic modeling system for short-term decision support of water control operations in real time. It encompasses data collection, validation and transformation, data storage, visualization, real time model simulation for decision-making support, and data dissemination. The system uses precipitation and flow data, collected in real-time, along with forecasted flow from the National Weather Service to model and optimize reservoir operations and forecast downstream flows and stages, providing communities accurate and timely information to aid their flood-fighting. This involves integrating several simulation modeling programs, including HEC-HMS to forecast flows, HEC-ResSim to model reservoir operations and HEC-RAS to compute forecasted stage hydrographs. An inundation boundary and depth map of water in the flood plain can be calculated from the HEC-RAS results using ArcInfo. By varying future precipitation and releases, engineers can evaluate different "What if?" scenarios. The effectiveness of this tool and Corps reservoirs are examined.

Investigating the Performance of One- and Two-dimensional Flood Models in a Channelized River Network: A Case Study of the Obion River System

NASA Astrophysics Data System (ADS)

Kalyanapu, A. J.; Dullo, T. T.; Thornton, J. C.; Auld, L. A.

2015-12-01

Obion River, is located in the northwestern Tennessee region, and discharges into the Mississippi River. In the past, the river system was largely channelized for agricultural purposes that resulted in increased erosion, loss of wildlife habitat and downstream flood risks. These impacts are now being slowly reversed mainly due to wetland restoration. The river system is characterized by a large network of "loops" around the main channels that hold water either from excess flows or due to flow diversions. Without data on each individual channel, levee, canal, or pond it is not known where the water flows from or to. In some segments along the river, the natural channel has been altered and rerouted by the farmers for their irrigation purposes. Satellite imagery can aid in identifying these features, but its spatial coverage is temporally sparse. All the alterations that have been done to the watershed make it difficult to develop hydraulic models, which could predict flooding and droughts. This is especially true when building one-dimensional (1D) hydraulic models compared to two-dimensional (2D) models, as the former cannot adequately simulate lateral flows in the floodplain and in complex terrains. The objective of this study therefore is to study the performance of 1D and 2D flood models in this complex river system, evaluate the limitations of 1D models and highlight the advantages of 2D models. The study presents the application of HEC-RAS and HEC-2D models developed by the Hydrologic Engineering Center (HEC), a division of the US Army Corps of Engineers. The broader impacts of this study is the development of best practices for developing flood models in channelized river systems and in agricultural watersheds.

Evaluation of multiple hydraulic models in generating design/near-real time flood inundation extents under various geophysical settings

NASA Astrophysics Data System (ADS)

Liu, Z.; Rajib, M. A.; Jafarzadegan, K.; Merwade, V.

2015-12-01

Application of land surface/hydrologic models within an operational flood forecasting system can provide probable time of occurrence and magnitude of streamflow at specific locations along a stream. Creating time-varying spatial extent of flood inundation and depth requires the use of a hydraulic or hydrodynamic model. Models differ in representing river geometry and surface roughness which can lead to different output depending on the particular model being used. The result from a single hydraulic model provides just one possible realization of the flood extent without capturing the uncertainty associated with the input or the model parameters. The objective of this study is to compare multiple hydraulic models toward generating ensemble flood inundation extents. Specifically, relative performances of four hydraulic models, including AutoRoute, HEC-RAS, HEC-RAS 2D, and LISFLOOD are evaluated under different geophysical conditions in several locations across the United States. By using streamflow output from the same hydrologic model (SWAT in this case), hydraulic simulations are conducted for three configurations: (i) hindcasting mode by using past observed weather data at daily time scale in which models are being calibrated against USGS streamflow observations, (ii) validation mode using near real-time weather data at sub-daily time scale, and (iii) design mode with extreme streamflow data having specific return periods. Model generated inundation maps for observed flood events both from hindcasting and validation modes are compared with remotely sensed images, whereas the design mode outcomes are compared with corresponding FEMA generated flood hazard maps. The comparisons presented here will give insights on probable model-specific nature of biases and their relative advantages/disadvantages as components of an operational flood forecasting system.

Palonosetron versus other 5-HT₃ receptor antagonists for prevention of chemotherapy-induced nausea and vomiting in patients with hematologic malignancies treated with emetogenic chemotherapy in a hospital outpatient setting in the United States.

PubMed

Craver, Chris; Gayle, Julie; Balu, Sanjeev; Buchner, Deborah

2011-01-01

This study evaluated the rate of uncontrolled chemotherapy-induced nausea and vomiting (CINV) after initiating antiemetic prophylaxis with palonosetron versus other 5-HT₃ receptor antagonists (RAs) in patients diagnosed with hematologic malignancies (lymphoma and leukemia) and receiving highly emetogenic chemotherapy (HEC) or moderately emetogenic chemotherapy (MEC) in a hospital outpatient setting. Patients aged ≥ 18 years and diagnosed with hematologic malignancies initiating HEC or MEC and antiemetic prophylaxis with palonosetron (Group 1) and other 5-HT₃ RAs (Group 2) for the first time in a hospital outpatient setting between 4/1/2007 and 3/31/2009 were identified from the Premier Perspective Database. Within each cycle, CINV events were identified (in the hospital outpatient, inpatient, and emergency room settings) through ICD-9 codes for nausea, vomiting, and/or volume depletion (from each CT administration day 1 until the end of the CT cycle), or use of rescue medications (day 2 until the end of the CT cycle). Negative binomial distribution generalized linear multivariate regression model estimating the CINV event rate on CT, specific CT cycles, and cancer diagnosis (leukemia/lymphoma)-matched groups in the follow-up period (first of 8 cycles or 6 months) was developed. Of 971 identified patients, 211 initiated palonosetron (Group 1). Group 1 patients comprised of more females [50.2 vs. 41.4%; p = 0.0226], Whites [74.4 vs. 70.4%, and Hispanics [7.6 vs. 6.3%; all races p = 0.0105], received more HEC treatments [89.6 vs. 84.2%; all CT types p = 0.0129], and had more lymphoma diagnosed patients [89.6 vs. 76.3%; all cancer types p = 0.0033] at baseline. After controlling for differences in several demographic and clinical variables, the regression model predicted a 20.4% decrease in CINV event rate per CT cycle for Group 1 versus Group 2 patients. Study limitations include potential lack of generalizability, absence of data on certain confounders including alcohol consumption and prior history of motion sickness, potential underestimation of incidence of uncontrolled CINV, and inability to draw conclusions pertaining to cause and effect relationship. In this retrospective hospital study, patients with hematologic malignancies treated with HEC or MEC and initiated on antiemetic prophylaxis with palonosetron in the hospital outpatient setting were more likely to experience significantly lower CINV event rates (in the hospital outpatient, inpatient, and emergency room settings) versus patients initiated on other 5-HT₃ RAs.

Further development and implementation of the DIWA distributed hydrological model-based integrated hydroinformatics system in the Danube River Basin for supporting decision making in water management

NASA Astrophysics Data System (ADS)

Szabó, J. A.; Réti, G. Z.; Tóth, T.

2012-04-01

Today, the most significant mission of the decision makers on integrated water management issues is to carry out sustainable management for sharing the resources between a variety of users and the environment under conditions of considerable uncertainty (such as climate/land use/population/etc. change) conditions. In light of this increasing water management complexity, we consider that the most pressing needs is to develop and implement up-to-date Spatial Decision Support Systems (SDSS) for aiding decision-making processes to improve water management. One of the most important parts of such an SDSS is a distributed hydrologic model-based integrated hydroinformatics system to analyze the different scenarios. The less successful statistical and/or empirical model-experiments of earlier decades have highlighted the importance of paradigm shift in hydrological modelling approach towards the physically based distributed models, to better describe the complex hydrological processes even on catchments of more ten thousands of square km. Answers to questions like what are the effects of human actions in the catchment area (e. g. forestation or deforestation) or the changing of climate/land use on the flood, drought, or water scarcity, or what is the optimal strategy for planning and/or operating reservoirs, have become increasingly important. Nowadays the answers to this kind of questions can be provided more easily than before. The progress of applied mathematical methods, the advanced state of computer technology as well as the development of remote sensing and meteorological radar technology have accelerated the research capable of answering these questions using well-designed integrated hydroinformatics systems. With most emphasis on the recent years of extensive scientific and computational development HYDROInform UnLtd developed a distributed hydrological model-based integrated hydroinformatics system for supporting the various decisions in water management. Our developed integrated model has two basic pillars: the DIWA (DIstributed WAtershed) hydrologic, and the well-known HEC-RAS hydraulic models. The DIWA is a dynamic water-balance model that distributed both in space and its parameters, and which was developed along combined principles but its mostly based on physical foundations. According to the philosophy of the distributed model approach the catchment is divided into basic elements, cells where the basin characteristics, parameters, physical properties, and the boundary conditions are applied in the centre of the cell, and the cell is supposed to be homogenous between the block boundaries. The neighbouring cells are connected to each other according to runoff hierarchy (local drain direction). Applying the hydrological mass balance and the adequate dynamic equations to these cells, the result is a distributed hydrological model on a continuous, 3D gridded domain. For calculating the water level as well the HEC-RASS hydraulic model has been embedded into DIWA model. In this integration the DIWA model provides the upper boundary conditions for HEC-RAS, and then HEC-RAS provides the water levels along the lowland parts of the river-network. In this presentation, our recently developed integrated hydroinformatics system and its implementation for the middle-upper part of the Danube River Basin will be reported. Following an outline of the backgrounds, an overview on the DIWA and the integrated model-system will be given. The implementation of this integrated hydroinformatics system in the Danube River Basin will also be presented, including a summary of the developed 1km resolution geo-dataset for the modelling. Then some demonstrative results of the use of the pre-calibrated system will be discussed. Finally, an outline of the future steps of the development will be discussed.

A characterization methodology for post-wildfire flood hazard assessments

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

McLin, Stephen G.; Van Eeckhout, M. E.; Springer, E. P.

A combined GIS-HEC modeling application for floodplain analysis of pre- and post-burned watersheds is described. The burned study area is located on Pajarito Plateau near Los Alamos, New Mexico (USA), where the Cerro Grande Wildfire burned 17,353 ha (42,878 ac) in May 2000. This area is dominated by rugged mountains that are dissected by numerous steep canyons having both ephemeral and perennial channel reaches. Vegetation consists of pinon-juniper woodlands located between 1,829-2,134 m (6,000-7,000 ft) above mean sea level (m MSL), and Ponderosa pine stands between 2,134-3,048 m MSL (7,000-10,000 ft). Approximately seventeen percent of the burned area is locatedmore » within Los Alamos National Laboratory, and the remainder is located in upstream or adjacent watersheds. Pre-burn floodplains were previously mapped in 1991-92 using early HEC models as part of the RCRA/HSWA permitting process. Numerous recording precipitation and stream gages have also been installed. These data provide essential information characterizing rainfall-runoff relationships before and after the fire. They are also being used to monitor spatial and temporal changes as forest recovery progresses. Post-burn changes in HEC-HMS predicted rainfall-runoff patterns are related to changes in watershed vegetation cover and hydrophobic soil conditions. Stream channel cross-sectional geometries were extracted from 0.3 m (1 ft) DEM data using ArcView GIS. Then floodpool topwidths, depths, and flow velocities were remapped using the HEC-RAS model. Finally, numerous surveyed channel sections were selectively made at crucial sites for model verification. Direct comparisons are made between alternative data acquisition and mapping techniques.« less

Integrated hazard assessment of Cirenmaco glacial lake in Zhangzangbo valley, Central Himalayas

NASA Astrophysics Data System (ADS)

Wang, Weicai; Gao, Yang; Iribarren Anacona, Pablo; Lei, Yanbin; Xiang, Yang; Zhang, Guoqing; Li, Shenghai; Lu, Anxin

2018-04-01

Glacial lake outburst floods (GLOFs) have recently become one of the primary natural hazards in the Himalayas. There is therefore an urgent need to assess GLOF hazards in the region. Cirenmaco, a moraine-dammed lake located in the upstream portion of Zhangzangbo valley, Central Himalayas, has received public attention after its damaging 1981 outburst flood. Here, by combining remote sensing methods, bathymetric survey and 2D hydraulic modeling, we assessed the hazard posed by Cirenmaco in its current status. Inter-annual variation of Cirenmaco lake area indicates a rapid lake expansion from 0.10 ± 0.08 km2 in 1988 to 0.39 ± 0.04 km2 in 2013. Bathymetric survey shows the maximum water depth of the lake in 2012 was 115 ± 2 m and the lake volume was calculated to be 1.8 × 107 m3. Field geomorphic analysis shows that Cirenmaco glacial lake is prone to GLOFs as mass movements and ice and snow avalanches can impact the lake and the melting of the dead ice in the moraine can lower the dam level. HEC-RAS 2D model was then used to simulate moraine dam failure of the Cirenmaco and assess GLOF impacts downstream. Reconstruction of Cirenmaco 1981 GLOF shows that HEC-RAS can produce reasonable flood extent and water depth, thus demonstrate its ability to effectively model complex GLOFs. GLOF modeling results presented can be used as a basis for the implementation of disaster prevention and mitigation measures. As a case study, this work shows how we can integrate different methods to GLOF hazard assessment.

[The Role of 5-Aza-CdR on Methylation of Promoter in RASSF1A Gene in Endometrial Carcinoma].

PubMed

Huang, Li-ping; Chen, Chen; Wang, Xue-ping; Liu, Hui

2015-05-01

To explore the effect of demethylating drug 5-Aza-2'-deoxycytidine (5-Aza-CdR) on methtylation status of the Ras-association domain familylA gene (RASSF1A) in human endometrial carcinoma. Randomly'assign the human endometrial carcinoma cell line HEC-1-B into groups and use demethylating drug 5-Aza-CdR of different concentration to treat them. Then Methylation-specific polymerase chain reaction (MSP), real-time PCR, Western blot, TUNEL technology were used to analyze methylation status of RASSF1A promoter CpG islands, RASSF1A mRNA expression, RASSF1A protein expression and apoptosis of HEC-1-B cell. High DNA methylation in RASSF1A gene promoter region, low RASSF1A mRNA level and protein expression and out of control of human endometrial carcinoma cell HEC-1-B apoptosis were observed. 5-Aza-CdR of different concentration could reverse RASSF1A gene's methylation status, recover the expression of mRNA and protein, and control the growth of HEC-1-B by inducing apoptosis. Aberrant methylation of RASSF1A in endometrial cancer as a therapeutic target, demethylating agent 5-Aza-CdR could be an effective way of gene therapy.

Hydrologic modeling of Guinale River Basin using HEC-HMS and synthetic aperture radar

NASA Astrophysics Data System (ADS)

Bien, Ferdinand E.; Plopenio, Joanaviva C.

2017-09-01

This paper presents the methods and results of hydrologic modeling of Guinale river basin through the use of HEC-HMS software and Synthetic Aperture Radar Digital Elevation Model (SAR DEM). Guinale River Basin is located in the province of Albay, Philippines which is one of the river basins covered by the Ateneo de Naga University (ADNU) Phil-LiDAR 1. This research project was funded by the Department of Science and Technology (DOST) through the Philippine Council for Industry, Energy and Emerging Technology Research and Development (PCIEERD). Its objectives are to simulate the hydrologic model of Guinale River basin using HEC-HMS software and SAR DEM. Its basin covers an area of 165.395 sq.km. and the hydrologic model was calibrated using the storm event typhoon Nona (international name Melor). Its parameter had undergone a series of optimization processes of HEC-HMS software in order to produce an acceptable level of model efficiency. The Nash-Sutcliffe (E), Percent Bias and Standard Deviation Ratio were used to measure the model efficiency, giving values of 0.880, 0.260 and 0.346 respectively which resulted to a "very good" performance rating of the model. The flood inundation model was simulated using Legazpi Rainfall Intensity Duration Frequency Curves (RIDF) and HEC-RAS software developed by the US Army corps of Engineers (USACE). This hydrologic model will provide the Municipal Disaster Risk Reduction Management Office (MDRRMO), Local Government units (LGUs) and the community a tool for the prediction of runoff in the area.

Robust Prediction of Hydraulic Roughness

DTIC Science & Technology

2011-03-01

Manning’s n were required as input for further hydraulic analyses with HEC - RAS . HYDROCAL was applied to compare different estimates of resistance... River Restoration Science Synthesis (NRRSS) demonstrated that, in 2007, river and stream restoration projects and funding were at an all time high...behavior makes this parameter very difficult to quan- tify repeatedly and accurately. A fundamental concept of hydraulic theory in the context of river

USACE Regional Sediment Management and Engineering with Nature 2013 Workshop Summary

DTIC Science & Technology

2014-08-01

Tools into HEC-RAS St. Louis Kaskaskia River Navigation Channel Mobile Biodegradable Containment Structures for RSM Honolulu Hawaii RSM – Haleiwa...sediment from USACE to private entities for use. Share successes and lessons learned.  Increase the use of vegetation and other biodegradable ...beaches, and submerged mounds) and construction materials (e.g., reef balls, combination of rock sills and oyster bags , native plants, and

Evaluating the effects of dam breach methodologies on Consequence Estimation through Sensitivity Analysis

NASA Astrophysics Data System (ADS)

Kalyanapu, A. J.; Thames, B. A.

2013-12-01

Dam breach modeling often includes application of models that are sophisticated, yet computationally intensive to compute flood propagation at high temporal and spatial resolutions. This results in a significant need for computational capacity that requires development of newer flood models using multi-processor and graphics processing techniques. Recently, a comprehensive benchmark exercise titled the 12th Benchmark Workshop on Numerical Analysis of Dams, is organized by the International Commission on Large Dams (ICOLD) to evaluate the performance of these various tools used for dam break risk assessment. The ICOLD workshop is focused on estimating the consequences of failure of a hypothetical dam near a hypothetical populated area with complex demographics, and economic activity. The current study uses this hypothetical case study and focuses on evaluating the effects of dam breach methodologies on consequence estimation and analysis. The current study uses ICOLD hypothetical data including the topography, dam geometric and construction information, land use/land cover data along with socio-economic and demographic data. The objective of this study is to evaluate impacts of using four different dam breach methods on the consequence estimates used in the risk assessments. The four methodologies used are: i) Froehlich (1995), ii) MacDonald and Langridge-Monopolis 1984 (MLM), iii) Von Thun and Gillete 1990 (VTG), and iv) Froehlich (2008). To achieve this objective, three different modeling components were used. First, using the HEC-RAS v.4.1, dam breach discharge hydrographs are developed. These hydrographs are then provided as flow inputs into a two dimensional flood model named Flood2D-GPU, which leverages the computer's graphics card for much improved computational capabilities of the model input. Lastly, outputs from Flood2D-GPU, including inundated areas, depth grids, velocity grids, and flood wave arrival time grids, are input into HEC-FIA, which provides the consequence assessment for the solution to the problem statement. For the four breach methodologies, a sensitivity analysis of four breach parameters, breach side slope (SS), breach width (Wb), breach invert elevation (Elb), and time of failure (tf), is conducted. Up to, 68 simulations are computed to produce breach hydrographs in HEC-RAS for input into Flood2D-GPU. The Flood2D-GPU simulation results were then post-processed in HEC-FIA to evaluate: Total Population at Risk (PAR), 14-yr and Under PAR (PAR14-), 65-yr and Over PAR (PAR65+), Loss of Life (LOL) and Direct Economic Impact (DEI). The MLM approach resulted in wide variability in simulated minimum and maximum values of PAR, PAR 65+ and LOL estimates. For PAR14- and DEI, Froehlich (1995) resulted in lower values while MLM resulted in higher estimates. This preliminary study demonstrated the relative performance of four commonly used dam breach methodologies and their impacts on consequence estimation.

Fifty-year flood-inundation maps for El Progreso, Honduras

USGS Publications Warehouse

Kresch, David L.; Mastin, Mark C.; Olsen, T.D.

2002-01-01

After the devastating floods caused by Hurricane Mitch in 1998, maps of the areas and depths of the 50-year-flood inundation at 15 municipalities in Honduras were prepared as a tool for agencies involved in reconstruction and planning. This report, which is one in a series of 15, presents maps of areas in the municipality of El Progreso that would be inundated by a 50-year flood of Rio Pelo. Geographic Information System (GIS) coverages of the flood inundation are available on a computer in the municipality of El Progreso as part of the Municipal GIS project and on the Internet at the Flood Hazard Mapping Web page (http://mitchnts1.cr.usgs.gov/projects/floodhazard.html). These coverages allow users to view the flood inundation in much more detail than is possible using the maps in this report. Water-surface elevations for a 50-year-flood on Rio Pelo at El Progreso were estimated using HEC-RAS, a one-dimensional, steady-flow, step-backwater computer program. The channel and floodplain cross sections used in HEC-RAS were developed from an airborne light-detection-and-ranging (LIDAR) topographic survey of the area. There are no nearby long-term stream-gaging stations on Rio Pelo; therefore, the 50-year-flood discharge for Rio Pelo, 235 cubic meters per second, was estimated using a regression equation that relates the 50-year-flood discharge to drainage area and mean annual precipitation. The drainage area and mean annual precipitation estimated for Rio Pelo at El Progreso are 47.4 square kilometers and 1,920 millimeters, respectively.

Fifty-year flood-inundation maps for Choloma, Honduras

USGS Publications Warehouse

Mastin, Mark C.; Olsen, T.D.

2002-01-01

After the devastating floods caused by Hurricane Mitch in 1998, maps of the areas and depths of the 50-year-flood inundation at 15 municipalities in Honduras were prepared as a tool for agencies involved in reconstruction and planning. This report, which is one in a series of 15, presents maps of areas in the municipality of Choloma that would be inundated by a 50-year flood of Rio Choloma. Geographic Information System (GIS) coverages of the flood inundation are available on a computer in the municipality of Choloma as part of the in the Municipal GIS project and on the Internet at the Flood Hazard Mapping Web page (http://mitchnts1.cr.usgs.gov/projects/floodhazard.html). These coverages allow users to view the flood inundation in much more detail than is possible using the maps in this report. Water-surface elevations for a 50-year-flood on Rio Choloma at Choloma were determined using HEC-RAS, a one-dimensional, steady-flow, step-backwater computer program. The channel and floodplain cross sections used in HEC-RAS were developed from an airborne light detection and ranging (LIDAR) topographic survey of the area. There are no nearby long-term stream-gaging stations on Rio Choloma; therefore, the 50-year-flood discharge for Rio Choloma, 370 cubic meters per second, was estimated using a regression equation that relates the 50-year-flood discharge to drainage area and mean annual precipitation. The drainage area and mean annual precipitation estimated for Rio Choloma at Choloma are 89.5 square kilometers and 2,164 millimeters, respectively.

Fifty-year flood-inundation maps for Catacamas, Honduras

USGS Publications Warehouse

Kresch, David L.; Mastin, Mark C.; Olsen, T.D.

2002-01-01

After the devastating floods caused by Hurricane Mitch in 1998, maps of the areas and depths of the 50-year-flood inundation at 15 municipalities in Honduras were prepared as a tool for agencies involved in reconstruction and planning. This report, which is one in a series of 15, presents maps of areas in the municipality of Catacamas that would be inundated by a 50-year-flood of Rio Catacamas. Geographic Information System (GIS) coverages of the flood inundation are available on a computer in the municipality of Catacamas as part of the Municipal GIS project and on the Internet at the Flood Hazard Mapping Web page (http://mitchnts1.cr.usgs.gov/projects/ floodhazard.html). These coverages allow users to view the flood inundation in much more detail than is possible using the maps in this report. Water-surface elevations for a 50-year-flood on Rio Catacamas at Catacamas were estimated using HEC-RAS, a one-dimensional, steady-flow, step-backwater computer program. The channel and floodplain cross sections used in HEC-RAS were developed from an airborne light-detection-and-ranging (LIDAR) topographic survey of the area. The 50-year-flood discharge for Rio Catacamas at Catacamas, 216 cubic meters per second, was estimated using a regression equation that relates the 50-year-flood discharge to drainage area and mean annual precipitation because there are no long-term stream-gaging stations on the river from which to estimate the discharge. The drainage area and mean annual precipitation estimated for Rio Catacamas at Catacamas are 45.4 square kilometers and 1,773 millimeters, respectively.

Fifty-year flood-inundation maps for Olanchito, Honduras

USGS Publications Warehouse

Kresch, David L.; Mastin, M.C.; Olsen, T.D.

2002-01-01

After the devastating floods caused by Hurricane Mitch in 1998, maps of the areas and depths of the 50-year-flood inundation at 15 municipalities in Honduras were prepared as a tool for agencies involved in reconstruction and planning. This report, which is one in a series of 15, presents maps of areas in the municipality of Olanchito that would be inundated by a 50-year-flood of Rio Uchapa. Geographic Information System (GIS) coverages of the flood inundation are available on a computer in the municipality of Olanchito as part of the Municipal GIS project and on the Internet at the Flood Hazard Mapping Web page (http://mitchnts1.cr.usgs.gov/projects/floodhazard.html). These coverages allow users to view the flood inundation in much more detail than is possible using the maps in this report. Water-surface elevations for a 50-year-flood discharge of 243 cubic meters per second on Rio Uchapa at Olanchito were estimated using HEC-RAS, a one-dimensional, steady-flow, step-backwater computer program. The channel and floodplain cross sections used in HEC-RAS were developed from an airborne light-detection-and-ranging (LIDAR) topographic survey of the area. There are no nearby long-term stream-gaging stations on Rio Uchapa; therefore, the 50-year-flood discharge for Rio Uchapa was estimated using a regression equation that relates the 50-year-flood discharge to drainage area and mean annual precipitation. The drainage area and mean annual precipitation estimated for Rio Uchapa at Olanchito are 97.1 square kilometers and 1,178 millimeters, respectively.

Fifty-year flood-inundation maps for La Ceiba, Honduras

USGS Publications Warehouse

Kresch, David L.; Mastin, M.C.; Olsen, T.D.

2002-01-01

After the devastating floods caused by Hurricane Mitch in 1998, maps of the areas and depths of the 50-year-flood inundation at 15 municipalities in Honduras were prepared as a tool for agencies involved in reconstruction and planning. This report, which is one in a series of 15, presents maps of areas in the municipality of La Ceiba that would be inundated by a 50-year-flood of Rio Cangrejal. Geographic Information System (GIS) coverages of the flood inundation are available on a computer in the municipality of La Ceiba as part of the Municipal GIS project and on the Internet at the Flood Hazard Mapping Web page (http://mitchnts1.cr.usgs.gov/projects/floodhazard.html). These coverages allow users to view the flood inundation in much more detail than is possible using the maps in this report. Water-surface elevations for a 50-year-flood discharge of 1,030 cubic meters per second on Rio Cangrejal at La Ceiba were computed using HEC-RAS, a one-dimensional, steady-flow, step-backwater computer program. The channel and floodplain cross sections used in HEC-RAS were developed from an airborne light-detection-and-ranging (LIDAR) topographic survey of the area. There are no nearby long-term stream-gaging stations on Rio Cangrejal; therefore, the 50-year-flood discharge for Rio Cangrejal at La Ceiba was estimated using a regression equation that relates the 50-year-flood discharge to drainage area and mean annual precipitation. The drainage area and mean annual precipitation estimated for Rio Cangrejal at La Ceiba are 498 square kilometers and 2,306 millimeters, respectively.

Quantifying Changes in Los Angeles River Breakout Triggered by Sea Level Rise Using a Hydrodynamic Model

NASA Astrophysics Data System (ADS)

Mallakpour, I.; Shakeri Majd, M.; AghaKouchak, A.; Moftakhari, H.; Sadegh, M.; Vahedifard, F.

2017-12-01

Sea Level Rise (SLR) has been identified as a global phenomenon that will challenge coastal communities and infrastructures through escalating risk of erosion and subsidence, as well as elevating storm surge heights. Overall, SLR not only increases frequency of future coastal flooding in low-land coastal areas, but also changes flow dynamics in rivers connected to oceans. Changes in flow dynamics (e.g., peaks, flow intensities) can elevate water surface profile locally, leading to river breakout and flooding. Quantifying river breakout provides invaluable information to local authorities when it comes to SLR mitigation and adaptation efforts. Los Angeles River (LAR) which is located in southern part of California is protected with levee systems. The focus of this study is about 18 miles of the river, starting from Pacific Ocean to Downtown Los Angeles, which protects residence and major infrastructures. We use the Hydrologic Engineering Center's River Analysis System (HEC-RAS) to simulate flow and its interactions with coastal water levels. HEC-RAS is capable of simulating flow in one- and two-dimensional systems, resolving Diffusive Wave Equation and Shallow Water Equation, respectively. In this study, the hydraulic model consists of one- and two-dimensional models connected through the LAR's levee system. This approach enables us to identify the onset of river breakout location alongside the LAR. The inflow data incorporated into the model obtained from a gage records and represents a significant event occurred in February 2005. This model utilizes a detail terrain model with 0.3 m LiDAR data. In order to explore effects of SLR associated with future climate changes on LAR and its levee system, two Representative Concentration Pathways (RCP of 4.5 and 8.5) are considered. Based on our RCPs, 24 projected SLRs are computed for future years (2030, 2050, and 2100) for three different quantiles. Our simulation results show SLR, which varies from 0.05 to 2.8 m, causes backwater at the mouth of the river, at Pacific Ocean. Consequently, flow velocities and depth changes in channel, which results in changes in onset and location of the river breakout. Our findings emphasize needs for incorporating effects of SLR in hydraulic models in order to support mitigation and adaption efforts.

Appropriate rehabilitation strategy for a traditional irrigation supply system: a case from the Babai area in Nepal.

PubMed

Adhikari, B; Verhoeven, R; Troch, P

2009-01-01

This paper studies primary canals of three traditional irrigation systems in the southern plains of Nepal. It offers a scientific interpretation of the indigenous technology applied to the systems, which facilitates to use the same channel network for irrigation, drainage and flood management. The flood management technology of the farmers by diverting as much discharge as possible to the field channels results in the reduction of discharge towards the downstream part of the main channel. It is depicted in the simulation study that uses the river analysis program HEC-RAS 4.0. A cascade of weirs is found to be the most cost effective and user-friendly option to upgrade these systems preserving the existing irrigation, drainage as well as flood management functions. This study suggests that the conventional irrigation design principles should be applied very cautiously with full knowledge of the existing socio-institutional setting, hydro-ecological regime and indigenous technology for upgrading any traditional irrigation system successfully. The indigenous flood management technology strengthens the emerging concept that the floods in the Ganges plain are to be managed, not controlled.

Improving a DSM Obtained by Unmanned Aerial Vehicles for Flood Modelling

NASA Astrophysics Data System (ADS)

Mourato, Sandra; Fernandez, Paulo; Pereira, Luísa; Moreira, Madalena

2017-12-01

According to the EU flood risks directive, flood hazard map must be used to assess the flood risk. These maps can be developed with hydraulic modelling tools using a Digital Surface Runoff Model (DSRM). During the last decade, important evolutions of the spatial data processing has been developed which will certainly improve the hydraulic models results. Currently, images acquired with Red/Green/Blue (RGB) camera transported by Unmanned Aerial Vehicles (UAV) are seen as a good alternative data sources to represent the terrain surface with a high level of resolution and precision. The question is if the digital surface model obtain with this data is adequate enough for a good representation of the hydraulics flood characteristics. For this purpose, the hydraulic model HEC-RAS was run with 4 different DSRM for an 8.5 km reach of the Lis River in Portugal. The computational performance of the 4 modelling implementations is evaluated. Two hydrometric stations water level records were used as boundary conditions of the hydraulic model. The records from a third hydrometric station were used to validate the optimal DSRM. The HEC-RAS results had the best performance during the validation step were the ones where the DSRM with integration of the two altimetry data sources.

[Carcinogenesis and its mechanism of mutant-type[12Asp]K-ras4B gene].

PubMed

Gui, Li-ming; Wei, Li-hui; Zhang, Ying-mei; Wang, Jian-liu; Wang, Ying; Chen, Ying; Ma, Da-long

2002-01-01

Ras gene plays an important role in the extra- and intra-cellular signal transduction pathway. It mediates series cascade reactions, and eventually actives transcriptional factors in nucleus. It is unknown on the mechanism of carcinogenesis of Ras gene in endometrial carcinoma, though K-ras mutant is very common in endometrial atypical hyperplasia and carcinoma. On basis of discovering the mutation in 12th codon of K-ras in endometrial carcinoma cell line, HEC-1A, we explored the carcinogenesis and molecular mechanism of mutant-type [12Asp] K-ras4B gene. (1) Full-length [12Asp]K-ras4B cDNA was amplified with RT-PCR, then inserted into pcDI eukaryotic expressive vector. (2) Morphological change, growth kinetics in vitro and tumorigencity in nude mice in vivo after-before transfection were observed. (3) To test the cell growth kinetics by methyl thiazolium tetrazolium (MTT) and [3H]thymidine incorporation method. (1) The authors have successfully constructed eukaryotic expression plasmid pcDI-[12Asp] K-ras4B; (2) To confirm that [12Asp] K-ras4B mutant can trigger the neoplastic transformation of NIH3T3 cells by test in vitro and in vivo. (3) After pMCV-RasN17 plasmid, a Ras mutant were transfected into pcDI-[12Asp] K-ras4B cells, the growth of this cell were restrained significantly in comparison with control group. (4) These findings indicate the expression of RafS621A resulted in remarkable inhibition in proliferation of pcDI-[12Asp]K-ras4B cell (P < 0.05). However, RafCAAX mutant can enhance pcDI-[12Asp]K-ras4B cell growth (P < 0.05). (1) [12Asp]K-ras4B gene alone is able to cause neoplastic transformation in NIH3T3 cells in vitro and in vivo. (2) [12Asp]K-ras4B-induced NIH3T3 cells neoplastic transformation required Raf signaling pathway.

Fifty-year flood-inundation maps for Siguatepeque, Honduras

USGS Publications Warehouse

Kresch, David L.; Mastin, Mark C.; Olsen, T.D.

2002-01-01

After the devastating floods caused by Hurricane Mitch in 1998, maps of the areas and depths of the 50-year-flood inundation at 15 municipalities in Honduras were prepared as a tool for agencies involved in reconstruction and planning. This report, which is one in a series of 15, presents maps of areas in the municipality of Siguatepeque that would be inundated by 50-year floods on Rio Selguapa, Rio Guique, Rio Celan, Rio Calan, and Quebrada Chalantuma. Geographic Information System (GIS) coverages of the flood inundation are available on a computer in the municipality of Siguatepeque as part of the Municipal GIS project and on the Internet at the Flood Hazard Mapping Web page (http://mitchnts1.cr.usgs.gov/projects/floodhazard.html). These coverages allow users to view the flood inundation in much more detail than is possible using the maps in this report. Water-surface elevations for 50-year-floods on each of the streams studied were computed using HEC-RAS, a one-dimensional, steady-flow, step-backwater computer program. The channel and floodplain cross sections used in HEC-RAS were developed from an airborne light-detection-and-ranging (LIDAR) topographic survey of the area and ground surveys at six bridges. There are no nearby long-term stream-gaging stations on any of the streams studied; therefore, the 50-year-flood discharges were estimated using a regression equation that relates the 50-year-flood discharge to drainage area and mean annual precipitation. The 50-year-flood discharges estimated for Rio Selguapa, Rio Guique, Rio Celan, Rio Calan, and Quebrada Chalantuma are 323, 168, 161, 146, and 90 cubic meters per second, respectively.

Fifty-year flood-inundation maps for Sonaguera, Honduras

USGS Publications Warehouse

Kresch, David L.; Mastin, Mark C.; Olsen, T.D.

2002-01-01

After the devastating floods caused by Hurricane Mitch in 1998, maps of the areas and depths of the 50-year-flood inundation at 15 municipalities in Honduras were prepared as a tool for agencies involved in reconstruction and planning. This report, which is one in a series of 15, presents maps of areas in the municipality of Sonaguera that would be inundated by a 50-year flood of Rio Sonaguera and its tributary, Rio Juan Lazaro. Geographic Information System (GIS) coverages of the flood inundation are available on a computer in the municipality of Sonaguera as part of the Municipal GIS project and on the Internet at the Flood Hazard Mapping Web page (http://mitchnts1.cr.usgs.gov/projects/floodhazard.html). These coverages allow users to view the flood inundation in much more detail than is possible using the maps in this report. Water-surface elevations for an estimated 50-year-flood on Rio Sonaguera and Rio Juan Lazaro at Sonaguera were determined using HEC-RAS, a one-dimensional, steady-flow, step-backwater computer program. The channel and floodplain cross sections used in HEC-RAS were developed from an airborne light-detection-and-ranging (LIDAR) topographic survey of the area and a ground survey at the bridge. There are no nearby long-term stream-gaging stations on Rio Sonaguera or Rio Juan Lazaro; therefore, the 50-year-flood discharge for Rio Sonaguera above the confluence with Rio Juan Lazaro, 194 cubic meters per second; for Rio Juan Lazaro at its mouth, 168 cubic meters per second, and for Rio Sonaguera at the downstream end of the study area, 282 cubic meters per second; were estimated using a regression equation that relates the 50-year-flood discharge to drainage area and mean annual precipitation.

Analysis of flood vulnerability in urban area; a case study in deli watershed

NASA Astrophysics Data System (ADS)

Indrawan, I.; Siregar, R. I.

2018-03-01

Based on the National Disaster Management Agency of Indonesia, the distribution of disasters and victims died until the year 2016 is the largest flood disaster. Deli River is a river that has the greatest flood potential through Medan City. In Deli Watershed, flow discharge affected by the discharge from its tributaries, the high rainfall intensity and human activity. We should anticipate reducing and preventing the occurrence of losses due to flood damage. One of the ways to anticipate flood disaster is to predict which part of urban area is would flood. The objective of this study is to analyze the flood inundation areas due to overflow of Deli River through Medan city. Two-dimensional modeling by HEC-RAS 5.0.3 is a widely used hydraulic software tool developed by the U.S Army Corps of Engineers, which combined with the HEC-HMS for hydrological modeling. The result shows flood vulnerability in Medan by a map to present the spot that vulnerable about flood. The flooded area due to the overflowing of Deli River consists of seven sub districts, namely Medan Johor, Medan Selayang, Medan Kota, Medan Petisah, Medan Maimun, Medan Perjuangan and Medan Barat.

Combining abiotic and biotic models - Hydraulical modeling to fill the gap between catchment and hydro-dynamic models

NASA Astrophysics Data System (ADS)

Guse, B.; Sulc, D.; Schmalz, B.; Fohrer, N.

2012-04-01

The European Water Framework Directive (WFD) requires a catchment-based approach, which is assessed in the IMPACT project by combining abiotic and biotic models. The core point of IMPACT is a model chain (catchment model -> 1-D-hydraulic model -> 3-D-hydro-morphodynamic model -> biotic habitat model) with the aim to estimate the occurrence of the target species of the WFD. Firstly, the model chain is developed for the current land use and climate conditions. Secondly, land use and climate change scenarios are developed at the catchment scale. The outputs of the catchment model for the scenarios are used as input for the next models within the model chain to estimate the effect of these changes on the target species. The eco-hydrological catchment model SWAT is applied for the Treene catchment in Northern Germany and delivers discharge and water quality parameters as a spatial explicit output for each subbasin. There is no water level information given by SWAT. However, water level values are needed as lower boundary condition for the hydro-dynamic and habitat models which are applied for the 300 m candidate reference reach. In order to fill the gap between the catchment and the hydro-morphodynamic model, the 1-D hydraulic model HEC-RAS is applied for a 3 km long reach transect from the next upstream hydrological station until the upper bound of the candidate study reach. The channel geometry for HEC-RAS was estimated based on 96 cross-sections which were measured in the IMPACT project. By using available discharge and water level measurements from the hydrological station and own flow velocity measurements, the channel resistence was estimated. HEC-RAS was run with different statistical indices (mean annual drought, mean discharge, …) for steady flow conditions. The rating curve was then constructed for the target cross-section, i.e. the lower bound of the candidate study reach, to fulfill the combining with the hydro- and morphodynamic models. These statistical indices can also be calculated for the discharge series provided by land use and climate scenarios. In this way, the effect of land use and climate change on the catchment and the hydraulic processes can be assessed.

Methodology for predicting maximum velocity and shear stress in a sinuous channel with bendway weirs using 1-D HEC-RAS modeling results

Treesearch

Paul Sclafani

2011-01-01

The Middle Rio Grande is a 29-mi reach of the Rio Grande River in central New Mexico that extends from downstream of Cochiti Dam to Bernalillo, New Mexico. A series of anthropogenic factors including the construction of flood control levees and Cochiti Dam have altered the historically-braided morphology of the Middle Rio Grande to a more sinuous, degrading reach, with...

Predicting floodplain boundary changes following the Cerro Grande wildfire

NASA Astrophysics Data System (ADS)

McLin, Stephen G.; Springer, Everett P.; Lane, Leonard J.

2001-10-01

A combined ArcView GIS-HEC modelling application for floodplain analysis of pre- and post-burned watersheds is described. The burned study area is located on Pajarito Plateau near Los Alamos National Laboratory (the Laboratory), where the Cerro Grande Wildfire burned 42 878 acres (17 352 ha) in May 2000. This area is dominated by rugged mountains that are dissected by numerous steep canyons having both ephemeral and perennial channel reaches. Vegetation consists of pinon-juniper woodlands located between 6000 and 7000 ft (1829-2134 m) above mean sea level (MSL), and Ponderosa pine stands between 7000 and 10000 ft MSL (2134-3048 m). Approximately 17% of the burned area is located within the Laboratory, and the remainder is located in upstream or adjacent watersheds. Pre-burn floodplains were previously mapped in 1990-91 using early HEC models as part of the hazardous waste site permitting process. Precipitation and stream gauge data provide essential information characterizing rainfall-runoff relationships before and after the fire. They also provide a means of monitoring spatial and temporal changes as forest recovery progresses. The 2000 summer monsoon began in late June and provided several significant runoff events for model calibration. HEC-HMS modelled responses were sequentially refined so that observed and predicted hydrograph peaks were matched at numerous channel locations. The 100 year, 6 h design storm was eventually used to predict peak hydrographs at critical sites. These results were compared with pre-fire simulations so that new flood-prone areas could be systematically identified. Stream channel cross-sectional geometries were extracted from a gridded 1 ft (0·3 m) digital elevation model (DEM) using ArcView GIS. Then floodpool topwidths, depths, and flow velocities were remapped using the HEC-RAS model. Finally, numerous surveyed channel sections were selectively made at crucial sites for DEM verification. These evaluations provided timely guidance that influenced the decision to construct several flood detention structures that were completed in September 2000. Published in 2001 John Wiley & Sons, Ltd.

Fifty-year flood-inundation maps for Choluteca, Honduras

USGS Publications Warehouse

Kresch, David L.; Mastin, Mark C.; Olsen, T.D.

2002-01-01

After the devastating floods caused by Hurricane Mitch in 1998, maps of the areas and depths of 50-year-flood inundation at 15 municipalities in Honduras were prepared as a tool for agencies involved in reconstruction and planning. This report, which is one in a series of 15, presents maps of areas in the municipality of Choluteca that would be inundated by 50-year floods on Rio Choluteca and Rio Iztoca. Geographic Information System (GIS) coverages of the flood inundation are available on a computer in the municipality of Choluteca as part of the Municipal GIS project and on the Internet at the Flood Hazard Mapping Web page (http://mitchnts1.cr.usgs.gov/projects/floodhazard.html). These coverages allow users to view the flood inundation in much more detail than is possible using the maps in this report. Water-surface elevations for 50-year-floods on Rio Choluteca and Rio Iztoca at Choluteca were estimated using HEC-RAS, a one-dimensional, steady-flow, step-backwater computer program. The channel and floodplain cross sections used in HEC-RAS were developed from an airborne light-detection-and-ranging (LIDAR) topographic survey of the area. The estimated 50-year-flood discharge for Rio Choluteca at Choluteca is 4,620 cubic meters per second, which is the drainage-area-adjusted weighted-average of two independently estimated 50-year-flood discharges for the gaging station Rio Choluteca en Puente Choluteca. One discharge, 4,913 cubic meters per second, was estimated from a frequency analysis of the 17 years of peak discharge record for the gage, and the other, 2,650 cubic meters per second, was estimated from a regression equation that relates the 50-year-flood discharge to drainage area and mean annual precipitation. The weighted-average of the two discharges at the gage is 4,530 cubic meters per second. The 50-year-flood discharge for the study area reach of Rio Choluteca was estimated by multiplying the weighted discharge at the gage by the ratio of the drainage areas upstream from the two locations. The 50-year-flood discharge for Rio Iztoca, which was estimated from the regression equation, is 430 cubic meters per second.

Fifty-year flood-inundation maps for Juticalpa, Honduras

USGS Publications Warehouse

Kresch, David L.; Mastin, M.C.; Olsen, T.D.

2002-01-01

After the devastating floods caused by Hurricane Mitch in 1998, maps of the areas and depths of 50-year-flood inundation at 15 municipalities in Honduras were prepared as a tool for agencies involved in reconstruction and planning. This report, which is one in a series of 15, presents maps of areas in the municipality of Juticalpa that would be inundated by a 50-year flood of Rio Juticalpa. Geographic Information System (GIS) coverages of the flood inundation are available on a computer in the municipality of Juticalpa as part of the Municipal GIS project and on the Internet at the Flood Hazard Mapping Web page (http://mitchnts1.cr.usgs.gov/projects/floodhazard.html). These coverages allow users to view the flood inundation in much more detail than is possible using the maps in this report. Water-surface elevations for a 50-year-flood on Rio Juticalpa at Juticalpa were estimated using HEC-RAS, a one-dimensional, steady-flow, step-backwater computer program. The channel and floodplain cross sections used in HEC-RAS were developed from an airborne light-detection-and-ranging (LIDAR) topographic survey of the area. The estimated 50-year-flood discharge for Rio Juticalpa at Juticalpa, 1,360 cubic meters per second, was computed as the drainage-area-adjusted weighted average of two independently estimated 50-year-flood discharges for the gaging station Rio Juticalpa en El Torito, located about 2 kilometers upstream from Juticalpa. One discharge, 1,551 cubic meters per second, was estimated from a frequency analysis of the 33 years of peak-discharge record for the gage, and the other, 486 cubic meters per second, was estimated from a regression equation that relates the 50-year-flood discharge to drainage area and mean annual precipitation. The weighted-average of the two discharges at the gage is 1,310 cubic meters per second. The 50-year flood discharge for the study area reach of Rio Juticalpa was estimated by multiplying the weighted discharge at the gage by the ratio of the drainage areas upstream from the two locations.

Flood study of the Suncook River in Epsom, Pembroke, and Allenstown, New Hampshire, 2009

USGS Publications Warehouse

Flynn, Robert H.

2010-01-01

On May 15, 2006, a breach in the riverbank caused an avulsion in the Suncook River in Epsom, NH. The breach in the riverbank and subsequent avulsion changed the established flood zones along the Suncook River; therefore, a new flood study was needed to reflect this change and aid in flood recovery and restoration. For this flood study, the hydrologic and hydraulic analyses for the Suncook River were conducted by the U.S. Geological Survey, in cooperation with the Federal Emergency Management Agency. This report presents water-surface elevations and profiles determined using the U.S. Army Corps of Engineers one-dimensional Hydrologic Engineering Center River Analysis System model, also known as HEC-RAS. Steady-state water-surface profiles were developed for the Suncook River from its confluence with the Merrimack River in the Village of Suncook (in Allenstown and Pembroke, NH) to the upstream corporate limit of the town of Epsom, NH (approximately 15.9 river miles). Floods of magnitudes that are expected to be equaled or exceeded once on the average during any 2-, 5-, 10-, 25-, 50-, 100-, or 500-year period (recurrence interval) were modeled using HEC-RAS. These flood events are referred to as the 2-, 5-, 10-, 25-, 50-, 100-, and 500-year floods and have a 50-, 20-, 10-, 4-, 2-, 1-, and 0.2-percent chance, respectively, of being equaled or exceeded during any year. The 10-, 50-, 100-, and 500-year flood events are important for flood-plain management, determination of flood-insurance rates, and design of structures such as bridges and culverts. The analyses in this study reflect flooding potentials that are based on existing conditions in the communities of Epsom, Pembroke, and Allenstown at the time of completion of this study (2009). Changes in the 100-year recurrence-interval flood elevation from the 1979 flood study were typically less than 2 feet with the exception of a location 900 feet upstream from the avulsion that, because of backwater from the dams in the abandoned channel, was 12 feet higher in the 1979 flood study than in this study.

Integration of contributed data with HEC-RAS hydrodynamic model for flood inundation and damage assessment: 2015 Dallas Texas Case Study

NASA Astrophysics Data System (ADS)

Sava, E.; Thornton, J. C.; Kalyanapu, A. J.; Cervone, G.

2016-12-01

Transportation infrastructure networks in urban areas are highly sensitive to natural disasters, yet are a very critical source for the success of rescue, recovery, and renovation operations. Therefore, prompt restoration of such networks is of high importance for disaster relief services. Satellite and aerial images provide data with high spatial and temporal resolution and are a powerful tool for monitoring the environment and mapping the spatio-temporal variability of the Earth's surface. They provide a synoptic overview and give useful environmental information for a wide range of scales, from entire continents to urban areas, with spatial pixel resolutions ranging from kilometers to centimeters. However, sensor limitations are often a serious drawback since no single sensor offers the optimal spectral, spatial, and temporal resolution at the same time. Specific data may not be collected in the time and space most urgently required and/or may it contain gaps as a result of the satellite revisit time, atmospheric opacity, or other obstructions. In this study, the feasibility of integrating multiple sources of contributed data including remotely sensed datasets and open-source geospatial datasets, into hydrodynamic models for flood inundation simulations is assessed. The 2015 Dallas floods that caused up to $61 million dollars in damage was selected for this study. A Hydraulic Engineering Center - River Analysis System (HEC-RAS) model was developed for the study area, using reservoir surcharge releases and geometry provided by the U.S. Army Corps of Engineers Fort Worth District. The simulated flood inundation is compared with the "contributed data" for the location (such as Civil Air Patrol data and WorldView 3 dataset) which indicated the model's lack of representing lateral inflows near the upstream section. An Artificial Neural Network (ANN) model is developed that used local precipitation and discharge values in the vicinity to estimate the lateral flows. This addition of estimated lateral inflows is expected to improve the model performance to match with the observed flows. Future work will focus on extending this preliminary work to assess the model performance after integrating these additional data sources.

Vulnerability Assessment Using LIDAR Data in Silang-Sta Rosa Subwatershed, Philippines

NASA Astrophysics Data System (ADS)

Bragais, M. A.; Magcale-Macandog, D. B.; Arizapa, J. L.; Manalo, K. M.

2016-10-01

Silang-Sta. Rosa Subwatershed is experiencing rapid urbanization. Its downstream area is already urbanized and the development is moving fast upstream. With the rapid land conversion of pervious to impervious areas and increase frequency of intense rainfall events, the downstream of the watershed is at risk of flood hazard. The widely used freeware HEC-RAS (Hydrologic Engineering Center- River Analysis System) model was used to implement the 2D unsteady flow analysis to develop a flood hazard map. The LiDAR derived digital elevation model (DEM) with 1m resolution provided detailed terrain that is vital for producing reliable flood extent map that can be used for early warning system. With the detailed information from the simulation like areas to be flooded, the predicted depth and duration, we can now provide specific flood forecasting and mitigation plan even at community level. The methodology of using 2D unsteady flow modelling and high resolution DEM in a watershed can be replicated to other neighbouring watersheds specially those areas that are not yet urbanized so that their development will be guided to be flood hazard resilient. LGUs all over the country will benefit from having a high resolution flood hazard map.

Molecularly imprinted polymer doped with Hectorite for selective recognition of sinomenine hydrochloride.

PubMed

Zhang, W; Fu, H L; Li, X Y; Zhang, H; Wang, N; Li, W; Zhang, X X

2016-01-01

In this work, a new and facile method was introduced to prepare molecularly imprinted polymers (MIPs) based on nano clay hectorite (Hec) for sinomenine hydrochloride (SM) analysis. Hec was firstly dissolved in distilled water in order to swell adequately, followed by a common precipitation polymerization with SM as the template, methacrylic acid as monomer, ethylene glycol dimethacrylate as a crosslinker and 2,2-azobisisobutyronitrile as an initiator. Hec@SM-MIPs were characterized by Fourier transform infrared spectrometer, transmission electron microscopy, scanning electron microscopy, energy dispersive X-ray spectroscopy and X-ray diffraction. The maximum binding capacity of Hec@SM-MIPs, SM-MIPs and non-imprinted polymers (NIPs) (Hec@NIPs) was 57.4, 16.8 and 11.6 mg/g, respectively. The reason for this result may be that Hec@SM-MIPs have more binding sites and imprinted cavities for template molecule. Equilibrium data were described by the Langmuir and Freundlich isotherm models. The results showed that the Hec@SM-MIPs adsorption data correlated better with the Langmuir equation than the Freundlich equation under the studied concentration range. In vitro drug release experiment, Hec@SM-MIPs have a better ability to control SM release than SM-MIPs. Therefore, Hec@SM-MIPs were successfully applied to extraction of SM and used as the materials for drug delivery system.

An uncertainty analysis of the flood-stage upstream from a bridge.

PubMed

Sowiński, M

2006-01-01

The paper begins with the formulation of the problem in the form of a general performance function. Next the Latin hypercube sampling (LHS) technique--a modified version of the Monte Carlo method is briefly described. The essential uncertainty analysis of the flood-stage upstream from a bridge starts with a description of the hydraulic model. This model concept is based on the HEC-RAS model developed for subcritical flow under a bridge without piers in which the energy equation is applied. The next section contains the characteristic of the basic variables including a specification of their statistics (means and variances). Next the problem of correlated variables is discussed and assumptions concerning correlation among basic variables are formulated. The analysis of results is based on LHS ranking lists obtained from the computer package UNCSAM. Results fot two examples are given: one for independent and the other for correlated variables.

An Integrated Ensemble-Based Operational Framework to Predict Urban Flooding: A Case Study of Hurricane Sandy in the Passaic and Hackensack River Basins

NASA Astrophysics Data System (ADS)

Saleh, F.; Ramaswamy, V.; Georgas, N.; Blumberg, A. F.; Wang, Y.

2016-12-01

Advances in computational resources and modeling techniques are opening the path to effectively integrate existing complex models. In the context of flood prediction, recent extreme events have demonstrated the importance of integrating components of the hydrosystem to better represent the interactions amongst different physical processes and phenomena. As such, there is a pressing need to develop holistic and cross-disciplinary modeling frameworks that effectively integrate existing models and better represent the operative dynamics. This work presents a novel Hydrologic-Hydraulic-Hydrodynamic Ensemble (H3E) flood prediction framework that operationally integrates existing predictive models representing coastal (New York Harbor Observing and Prediction System, NYHOPS), hydrologic (US Army Corps of Engineers Hydrologic Modeling System, HEC-HMS) and hydraulic (2-dimensional River Analysis System, HEC-RAS) components. The state-of-the-art framework is forced with 125 ensemble meteorological inputs from numerical weather prediction models including the Global Ensemble Forecast System, the European Centre for Medium-Range Weather Forecasts (ECMWF), the Canadian Meteorological Centre (CMC), the Short Range Ensemble Forecast (SREF) and the North American Mesoscale Forecast System (NAM). The framework produces, within a 96-hour forecast horizon, on-the-fly Google Earth flood maps that provide critical information for decision makers and emergency preparedness managers. The utility of the framework was demonstrated by retrospectively forecasting an extreme flood event, hurricane Sandy in the Passaic and Hackensack watersheds (New Jersey, USA). Hurricane Sandy caused significant damage to a number of critical facilities in this area including the New Jersey Transit's main storage and maintenance facility. The results of this work demonstrate that ensemble based frameworks provide improved flood predictions and useful information about associated uncertainties, thus improving the assessment of risks as when compared to a deterministic forecast. The work offers perspectives for short-term flood forecasts, flood mitigation strategies and best management practices for climate change scenarios.

Application of HEC-RAS for flood forecasting in perched river-A case study of hilly region, China

NASA Astrophysics Data System (ADS)

Sun, Pingping; Wang, Shuqian; Gan, Hong; Liu, Bin; Jia, Ling

2017-04-01

Flooding in small and medium rivers are seriously threatening the safety of human beings’ life and property. The simulation forecasting of the river flood and bank risk in hilly region has gradually become a hotspot. At present, there are few studies on the simulation of hilly perched river, especially in the case of lacking section flow data. And the method of how to determine the position of the levee breach along the river bank is not much enough. Based on the characteristics of the sections in hilly perched river, an attempt is applied in this paper which establishes the correlation between the flow profile computed by HEC-RAS model and the river bank. A hilly perched river in Lingshi County, Shanxi Province of China, is taken as the study object, the levee breach positions along the bank are simulated under four different design storm. The results show that the flood control standard of upper reach is high, which can withstand the design storm of 100 years. The current standard of lower reach is low, which is the flooding channel with high frequency. As the standard of current channel between the 2rd and the 11th section is low, levee along that channel of the river bank is considered to be heighten and reinforced. The study results can provide some technical support for flood proofing in hilly region and some reference for the reinforcement of river bank.

Redesigning reservoir compensation releases for ecological beenfit

NASA Astrophysics Data System (ADS)

Maynard, Carly

2010-05-01

River regulation is commonplace in England and much of the UK. Regulation for the purposes of public water supply causes flows downstream of a reservoir to be attenuated and the flow regime of the channel to be altered. The impact of channel impoundment on a small, upland UK river, has been assessed and methods for mitigation of ecological impacts explored. The method utilised a unique macroinvertebrate data set for pre- and post-impoundment periods to quantify the impact of Derwent Reservoir and the steady, continuous compensation release into the River Derwent, Northumberland. Impacts on the hydrological regime were also investigated and links drawn between changes in flow regime and changes in macroinvertebrate richness and diversity as a result of impoundment. In response to the claim that the impoundment has caused a change in flow regime and had deleterious effects on fish and macroinvertebrates, a compensation redesign tool (CRAB: Compensation Release Assessment at the Broad scale) was employed to design new compensation release regimes from the reservoir which account for the seasonal flow requirements of a number of key fish species. The impact of impoundment on the current flow regime was modelled and the impacts of predicted new regimes were predicted, using a 1D hydrodynamic model (HEC-RAS), as part of a modelling process known as CRAM (Compensation Release Assessment at the Meso-scale). Depth and velocity were the foci of the analysis as they are the two habitat requirements most well documented for the fish species in question, they could be modelled using HEC-RAS and they can act as surrogates for other habitat parameters such as temperature and substrate. The suitability of the depth and velocity combinations predicted using the HEC-RAS model were assessed using fuzzy-rule based modelling, which allowed the habitat quality of a given parameter combination to be quantified. Based on the results of the investigation it was concluded that there has been a change in flow regime and in ecological community structure since impoundment. The flow regime of the River Derwent has become less flashy with fewer extreme events, while macroinvertebrate richness and diversity have increased. The new flow regimes that were designed by CRAB, based on the depth and velocity requirements of brown trout, grayling and Atlantic salmon were predicted through CRAM to have minimal benefits for the fish populations of the River Derwent and it was concluded that no changes to flow regime should be made based solely on the assessment of habitat for fish. Impacts for the macroinvertebrate communities must also be considered as well as the impacts on other aspects of fish habitat including temperature, substrate and cover. A more detailed, micro-scale investigation into the effects of changing flow regime would be required to warrant a change in compensation release regime from Derwent Reservoir.

Impact of sea level rise on tide gate function.

PubMed

Walsh, Sean; Miskewitz, Robert

2013-01-01

Sea level rise resulting from climate change and land subsidence is expected to severely impact the duration and associated damage resulting from flooding events in tidal communities. These communities must continuously invest resources for the maintenance of existing structures and installation of new flood prevention infrastructure. Tide gates are a common flood prevention structure for low-lying communities in the tidal zone. Tide gates close during incoming tides to prevent inundation from downstream water propagating inland and open during outgoing tides to drain upland areas. Higher downstream mean sea level elevations reduce the effectiveness of tide gates by impacting the hydraulics of the system. This project developed a HEC-RAS and HEC-HMS model of an existing tide gate structure and its upland drainage area in the New Jersey Meadowlands to simulate the impact of rising mean sea level elevations on the tide gate's ability to prevent upstream flooding. Model predictions indicate that sea level rise will reduce the tide gate effectiveness resulting in longer lasting and deeper flood events. The results indicate that there is a critical point in the sea level elevation for this local area, beyond which flooding scenarios become dramatically worse and would have a significantly negative impact on the standard of living and ability to do business in one of the most densely populated areas of America.

Pool Formation in Boulder-Bed Streams: Implications From 1-D and 2-D Numerical Modeling

NASA Astrophysics Data System (ADS)

Harrison, L. R.; Keller, E. A.

2003-12-01

In mountain rivers of Southern California, boulder-large roughness elements strongly influence flow hydraulics and pool formation and maintenance. In these systems, boulders appear to control the stream morphology by converging flow and producing deep pools during channel forming discharges. Our research goal is to develop quantitative relationships between boulder roughness elements, temporal patterns of scour and fill, and geomorphic processes that are important in producing pool habitat. The longitudinal distribution of shear stress, unit stream power and velocity were estimated along a 48 m reach on Rattlesnake Creek, using the HEC-RAS v 3.0 and River 2-D numerical models. The reach has an average slope of 0.02 and consists of a pool-riffle sequence with a large boulder constriction directly above the pool. Model runs were performed for a range of stream discharges to test if scour and fill thresholds for pool and riffle environments could be identified. Results from the HEC-RAS simulations identified that thresholds in shear stress, unit stream power and mean velocity occur above a discharge of 5.0 cms. Results from the one-dimensional analysis suggest that the reversal in competency is likely due to changes in cross-sectional width at varying flows. River 2-D predictions indicated that strong transverse velocity gradients were present through the pool at higher modeled discharges. At a flow of 0.5 cms (roughly 1/10th bankfull discharge), velocities are estimated at 0.6 m/s and 1.3 m/s for the pool and riffle, respectively. During discharges of 5.15 cms (approximate bankfull discharge), the maximum velocity in the pool center increased to nearly 3.0 m/s, while the maximum velocity over the riffle is estimated at approximately 2.5 cms. These results are consistent with those predicted by HEC-RAS, though the reversal appears to be limited to a narrow jet that occurs through the pool head and pool center. Model predictions suggest that the velocity reversal is produced by a boulder-bedrock constriction that rapidly decreases the channel width above the pool by roughly 25 percent. The width constriction creates highly turbulent flow capable of scouring bed material through the pool. The high velocity core that is produced through the pool center appears to be enhanced by the formation of a large eddy directly below the boulder. Values of unit stream power and shear stress indicate that the pool exit is an area of deposition of bed material due to a decrease in tractive force. The presence of a strong transverse velocity gradient suggests that only a portion of the flow is responsible for scouring bed material. After we eliminate the dead water zone, the lowest five percent of the velocity range, patterns of effective width between pools and riffles begin to emerge. The ratio of flow width between adjacent pools and riffles is one measure of flow convergence. At a discharge of 0.5 cms, the ratio of effective width between pools and riffles is roughly 1:1, implying that there is uniform flow with little flow convergence. At a discharge of 5.15 cms the width ratio between the pool and riffle is about 1:3, demonstrating the strong convergent flow patterns at the pool head. The observed effective width relationship suggests that when considering restoration designs, boulders should be placed in areas that replicate natural convergence and divergence patterns in order to maximize pool area and depth.

Numerical Model Study of the Tuscarawas River below Dover Dam, Ohio

DTIC Science & Technology

2009-09-01

chl.erdc.usace.army.mil/sms). Cross-sections from a ERDC/CHL TR-09-17 7 HEC - RAS model provided by the district, along with aerial photographs for proper alignment...ER D C/ CH L TR -0 9 -1 7 Numerical Model Study of the Tuscarawas River below Dover Dam, Ohio Richard L. Stockstill and Jane M. Vaughan...September 2009 C oa st al a n d H yd ra u lic s La b or at or y Approved for public release; distribution is unlimited. ERDC/CHL TR-09

Development of a HEC-RAS temperature model for the North Santiam River, northwestern Oregon

USGS Publications Warehouse

Stonewall, Adam J.; Buccola, Norman L.

2015-01-01

Much of the error in temperature predictions resulted from the model’s inability to accurately simulate the full range of diurnal fluctuations during the warmest months. Future iterations of the model could be improved by the collection and inclusion of additional streamflow and temperature data, especially near the mouth of the South Santiam River. Presently, the model is able to predict hourly and daily water temperatures under a wide variety of conditions with a typical error of 0.8 and 0.7 °C, respectively.

Fifty-year flood-inundation maps for Tocoa, Honduras

USGS Publications Warehouse

Kresch, David L.; Mastin, Mark C.; Olsen, T.D.

2002-01-01

After the devastating floods caused by Hurricane Mitch in 1998, maps of the areas and depths of the 50-year-flood inundation at 15 municipalities in Honduras were prepared as a tool for agencies involved in reconstruction and planning. This report, which is one in a series of 15, presents maps of areas in the municipality of Tocoa that would be inundated by a 50-year flood of Rio Tocoa. Geographic Information System (GIS) coverages of the flood inundation are available on a computer in the municipality of Tocoa as part of the Municipal GIS project and on the Internet at the Flood Hazard Mapping Web page (http://mitchnts1.cr.usgs.gov/projects/floodhazard.html). These coverages allow users to view the flood inundation in much more detail than is possible using the maps in this report. Water-surface elevations for an estimated 50-year-flood on Rio Tocoa at Tocoa were estimated using HEC-RAS, a one-dimensional, steady-flow, step-backwater computer program. The channel and floodplain cross sections used in HEC-RAS were developed from an airborne light-detection-and-ranging (LIDAR) topographic survey of the area and a ground survey at one bridge. There are no nearby long-term stream-gaging stations on Rio Tocoa; therefore, the 50-year-flood discharge for Rio Tocoa, 552 cubic meters per second, was estimated using a regression equation that relates the 50-year-flood discharge to drainage area and mean annual precipitation. The drainage area and mean annual precipitation estimated for Rio Tocoa at Tocoa are 204 square kilometers and 1,987 millimeters, respectively. It was assumed that a portion of the 50-year flood, 200 cubic meters per second, would escape the main channel and flow down a side channel before re-entering the main channel again near the lower end of the study area.

Fifty-year flood-inundation maps for Tegucigalpa, Honduras

USGS Publications Warehouse

Mastin, Mark C.; Olsen, T.D.

2002-01-01

After the devastating floods caused by Hurricane Mitch in 1998, maps of the areas and depths of the 50-year-flood inundation at 15 municipalities in Honduras were prepared as a tool for agencies involved in reconstruction and planning. This report, which is one in a series of 15, presents maps of areas in the municipality of Tegucigalpa that would be inundated by a 50-year flood of Rio Choluteca, Rio Grande, Rio Guacerique, and Rio Chiquito. Geographic Information System (GIS) coverages of the flood inundation are available on a computer in the municipality of Tegucigalpa as part of the Municipal GIS project and on the Internet at the Flood Hazard Mapping Web page (http://mitchnts1.cr.usgs.gov/projects/floodhazard.html). These coverages allow users to view the flood inundation in much more detail than is possible using the maps in this report. Water-surface elevations for an estimated 50-year-flood on Rio Choluteca, Rio Grande, Rio Guacerique, and Rio Chiquito at Tegucigalpa were determined using HEC-RAS, a one-dimensional, steady-flow, step-backwater computer program. The channel and floodplain cross sections used in HEC-RAS were developed from an airborne light-detection-and-ranging (LIDAR) topographic survey of the area and ground surveys at bridges. There are no nearby long-term stream-gaging stations; therefore, the 50-year-flood discharges were estimated using a regression equation that relates the 50-year-flood discharge to drainage area and mean annual precipitation. The estimated 50-year-flood discharge is 922 cubic meters per second at Rio Choluteca at downstream end of the study area boundary, 663 cubic meters per second at the mouth of the Rio Grande, 475 cubic meters per second at the mouth of the Rio Guacerique, and 254 cubic meters per second at the mouth of the Rio Chiquito.

A coupled hydrological-hydraulic flood inundation model calibrated using post-event measurements and integrated uncertainty analysis in a poorly gauged Mediterranean basin

NASA Astrophysics Data System (ADS)

Hdeib, Rouya; Abdallah, Chadi; Moussa, Roger; Colin, Francois

2017-04-01

Developing flood inundation maps of defined exceedance probabilities is required to provide information on the flood hazard and the associated risk. A methodology has been developed to model flood inundation in poorly gauged basins, where reliable information on the hydrological characteristics of floods are uncertain and partially captured by the traditional rain-gauge networks. Flood inundation is performed through coupling a hydrological rainfall-runoff (RR) model (HEC-HMS) with a hydraulic model (HEC-RAS). The RR model is calibrated against the January 2013 flood event in the Awali River basin, Lebanon (300 km2), whose flood peak discharge was estimated by post-event measurements. The resulting flows of the RR model are defined as boundary conditions of the hydraulic model, which is run to generate the corresponding water surface profiles and calibrated against 20 post-event surveyed cross sections after the January-2013 flood event. An uncertainty analysis is performed to assess the results of the models. Consequently, the coupled flood inundation model is simulated with design storms and flood inundation maps are generated of defined exceedance probabilities. The peak discharges estimated by the simulated RR model were in close agreement with the results from different empirical and statistical methods. This methodology can be extended to other poorly gauged basins facing common stage-gauge failure or characterized by floods with a stage exceeding the gauge measurement level, or higher than that defined by the rating curve.

[Transforming gene in human esophageal carcinoma tissue].

PubMed

Jiang, W

1988-09-01

The transforming gene in human esophageal carcinoma (HEC) tissues collected from Lin-xian county, a high incidence area of esophageal cancer was studied. Eight primary HEC tissues were used as sources for the preparation of DNA. High molecular weight DNAs were separately added to NIH 3T3 cells by the calcium phosphate coprecipitation method. Of the 8 HEC tissues examined, 3 DNAs showed transforming activity and produced secondary transformants. The use of uncloned NIH 3T3 cells resulted in the appearances of non-transforming. The efficiency of primary transfection foci was low (0.025--0.05 focus per ug of DNA). In the secondary transfection, the efficiency was increased (0.30 focus per ug of DNA). The primary and secondary transformants were capable of forming colonies in soft agar (0.33%) in contrast to the control NIH 3T3 cells, which did not show any anchorage-independent growth. About 1 X 10(6) cells of the cloned secondary transformants were injected subcutaneously into athymic BALB/c nude mice. The mice developed large tumors (approximately 20-30 mm in diameter) within 5--15 days after injection. No tumor developed in mice injected with control NIH 3T3 cells even after 2 months. The transforming DNA had a linkage to the Alu sequence, indicating that a common human DNA fragment is conserved in the tumors. H-ras was found in the transforming DNA using Southern blot assay.

Fifty-year flood-inundation maps for Nacaome, Honduras

USGS Publications Warehouse

Kresch, David L.; Mastin, M.C.; Olsen, T.D.

2002-01-01

After the devastating floods caused by Hurricane Mitch in 1998, maps of the areas and depths of 50-year-flood inundation at 15 municipalities in Honduras were prepared as a tool for agencies involved in reconstruction and planning. This report, which is one in a series of 15, presents maps of areas in the municipality of Nacaome that would be inundated by 50-year floods on Rio Nacaome, Rio Grande, and Rio Guacirope. Geographic Information System (GIS) coverages of the flood inundation are available on a computer in the municipality of Nacaome as part of the Municipal GIS project and on the Internet at the Flood Hazard Mapping Web page (http://mitchnts1.cr.usgs.gov/projects/floodhazard.html). These coverages allow users to view the flood inundation in much more detail than is possible using the maps in this report. Water-surface elevations for 50-year-floods on Rio Nacaome, Rio Grande, and Rio Guacirope at Nacaome were computed using HEC-RAS, a one-dimensional, steady-flow, step-backwater computer program. The channel and floodplain cross sections used in HEC-RAS were developed from an airborne light-detection-and-ranging (LIDAR) topographic survey of the area and ground surveys at two bridges. The estimated 50-year-flood discharge for Rio Nacaome at Nacaome, 5,040 cubic meters per second, was computed as the drainage-area-adjusted weighted average of two independently estimated 50-year-flood discharges for the gaging station Rio Nacaome en Las Mercedes, located about 13 kilometers upstream from Nacaome. One of the discharges, 4,549 cubic meters per second, was estimated from a frequency analysis of the 16 years of peak-discharge record for the gage, and the other, 1,922 cubic meters per second, was estimated from a regression equation that relates the 50-year-flood discharge to drainage area and mean annual precipitation. The weighted-average of the two discharges is 3,770 cubic meters per second. The 50-year-flood discharges for Rio Grande, 3,890 cubic meters per second, and Rio Guacirope, 1,080 cubic meters per second, were also computed by adjusting the weighted-average 50-year-flood discharge for the Rio Nacaome en Las Mercedes gaging station for the difference in drainage areas between the gage and these river reaches.

Prostaglandin receptor EP3 regulates cell proliferation and migration with impact on survival of endometrial cancer patients

PubMed Central

Zhu, Junyan; Trillsch, Fabian; Mayr, Doris; Kuhn, Christina; Rahmeh, Martina; Hofmann, Simone; Vogel, Marianne; Mahner, Sven; Jeschke, Udo; von Schönfeldt, Viktoria

2018-01-01

Background Prostaglandin E2 (PGE2) receptor 3 (EP3) regulates tumor cell proliferation, migration, and invasion in numerous cancers. The role of EP3 as a prognostic biomarker in endometrial cancer remains unclear. The primary aim of this study was to analyze the prognostic significance of EP3 expression in endometrial cancer. Methods We analyzed the EP3 expression of 140 endometrial carcinoma patients by immunohistochemistry. RL95-2 endometrial cancer cell line was chosen from four endometrial cancer cell lines (RL95-2, Ishikawa, HEC-1-A, and HEC-1-B) according to EP3 expression level. Treated with PGE2 and EP3 antagonist, RL95-2 cells were investigated by MTT, BrdU, and wound healing assay for functional assessment of EP3. Results EP3 staining differed significantly according to WHO tumor grading in both whole cohort (p = 0.01) and the subgroup of endometrioid carcinoma (p = 0.01). Patients with high EP3 expression in their respective tumors had impaired progression-free survival as well as overall survival in both cohorts above. EP3 expression in the overall cohort was identified as an independent prognostic marker for progression-free survival (HR 1.014, 95%CI 1.003-1.024, p = 0.01) when adjusted for age, stage, grading, and recurrence. Treatment with EP3 antagonists induced upregulation of estrogen receptor β and decreased activity of Ras and led to attenuated proliferation and migration of RL95-2 cells. Conclusions EP3 seems to play a crucial role in endometrial cancer progression. In the context of limited systemic treatment options for endometrial cancer, this explorative analysis identifies EP3 as a potential target for diagnostic workup and therapy. PMID:29416671

Prostaglandin receptor EP3 regulates cell proliferation and migration with impact on survival of endometrial cancer patients.

PubMed

Zhu, Junyan; Trillsch, Fabian; Mayr, Doris; Kuhn, Christina; Rahmeh, Martina; Hofmann, Simone; Vogel, Marianne; Mahner, Sven; Jeschke, Udo; von Schönfeldt, Viktoria

2018-01-02

Prostaglandin E2 (PGE2) receptor 3 (EP3) regulates tumor cell proliferation, migration, and invasion in numerous cancers. The role of EP3 as a prognostic biomarker in endometrial cancer remains unclear. The primary aim of this study was to analyze the prognostic significance of EP3 expression in endometrial cancer. We analyzed the EP3 expression of 140 endometrial carcinoma patients by immunohistochemistry. RL95-2 endometrial cancer cell line was chosen from four endometrial cancer cell lines (RL95-2, Ishikawa, HEC-1-A, and HEC-1-B) according to EP3 expression level. Treated with PGE2 and EP3 antagonist, RL95-2 cells were investigated by MTT, BrdU, and wound healing assay for functional assessment of EP3. EP3 staining differed significantly according to WHO tumor grading in both whole cohort (p = 0.01) and the subgroup of endometrioid carcinoma (p = 0.01). Patients with high EP3 expression in their respective tumors had impaired progression-free survival as well as overall survival in both cohorts above. EP3 expression in the overall cohort was identified as an independent prognostic marker for progression-free survival (HR 1.014, 95%CI 1.003-1.024, p = 0.01) when adjusted for age, stage, grading, and recurrence. Treatment with EP3 antagonists induced upregulation of estrogen receptor β and decreased activity of Ras and led to attenuated proliferation and migration of RL95-2 cells. EP3 seems to play a crucial role in endometrial cancer progression. In the context of limited systemic treatment options for endometrial cancer, this explorative analysis identifies EP3 as a potential target for diagnostic workup and therapy.

Buried waste integrated demonstration human engineered control station. Final report

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

Not Available

1994-09-01

This document describes the Human Engineered Control Station (HECS) project activities including the conceptual designs. The purpose of the HECS is to enhance the effectiveness and efficiency of remote retrieval by providing an integrated remote control station. The HECS integrates human capabilities, limitations, and expectations into the design to reduce the potential for human error, provides an easy system to learn and operate, provides an increased productivity, and reduces the ultimate investment in training. The overall HECS consists of the technology interface stations, supporting engineering aids, platform (trailer), communications network (broadband system), and collision avoidance system.

A geomorphic approach to 100-year floodplain mapping for the Conterminous United States

NASA Astrophysics Data System (ADS)

Jafarzadegan, Keighobad; Merwade, Venkatesh; Saksena, Siddharth

2018-06-01

Floodplain mapping using hydrodynamic models is difficult in data scarce regions. Additionally, using hydrodynamic models to map floodplain over large stream network can be computationally challenging. Some of these limitations of floodplain mapping using hydrodynamic modeling can be overcome by developing computationally efficient statistical methods to identify floodplains in large and ungauged watersheds using publicly available data. This paper proposes a geomorphic model to generate probabilistic 100-year floodplain maps for the Conterminous United States (CONUS). The proposed model first categorizes the watersheds in the CONUS into three classes based on the height of the water surface corresponding to the 100-year flood from the streambed. Next, the probability that any watershed in the CONUS belongs to one of these three classes is computed through supervised classification using watershed characteristics related to topography, hydrography, land use and climate. The result of this classification is then fed into a probabilistic threshold binary classifier (PTBC) to generate the probabilistic 100-year floodplain maps. The supervised classification algorithm is trained by using the 100-year Flood Insurance Rated Maps (FIRM) from the U.S. Federal Emergency Management Agency (FEMA). FEMA FIRMs are also used to validate the performance of the proposed model in areas not included in the training. Additionally, HEC-RAS model generated flood inundation extents are used to validate the model performance at fifteen sites that lack FEMA maps. Validation results show that the probabilistic 100-year floodplain maps, generated by proposed model, match well with both FEMA and HEC-RAS generated maps. On average, the error of predicted flood extents is around 14% across the CONUS. The high accuracy of the validation results shows the reliability of the geomorphic model as an alternative approach for fast and cost effective delineation of 100-year floodplains for the CONUS.

Northrop Grumman HEC flight coaxial cryocoolers performance

NASA Astrophysics Data System (ADS)

Nguyen, T.; Russo, J.; Basel, G.; Chi, D.; Abelson, L.

2018-05-01

The Northrop Grumman Aerospace Systems (NGAS) has expanded the cryocooler product line to include a single stage High Efficiency Cryocooler (HEC) cooler with a coaxial pulse tube cold head that operates at temperatures down to 45K. The HEC coaxial pulse tube cooler has been adopted by several customers, and has completed acceptance testing to meet program flight requirements. The NGAS TRL 9 HEC is a pulse tube cryocooler with a flexure bearing compressor which has been delivered for a number of flight payloads that are currently operating in space. To date, NGAS has delivered space cryocoolers in several configurations including single stage with a linear cold head and two stage with both linear and coaxial cold heads. The new HEC coaxial cooler uses the same TRL9 HEC compressor with a passive pulse tube cold head, to maintain the flight heritage of the HEC linear cooler. In this paper, we present the flight acceptance test data of the HEC coaxial cryocooler, which includes thermal performance, launch vibration and thermal cycling. The HEC coaxial cooler has demonstrated excellent performance in family with the flight qualified HEC linear cooler. The HEC coaxial cooler provides users with additional flexibility in selecting the cold head configuration to meet their particular applications.

Simulations of flow and prediction of sediment movement in Wymans Run, Cochranton Borough, Crawford County, Pennsylvania

USGS Publications Warehouse

Hittle, Elizabeth

2011-01-01

In small watersheds, runoff entering local waterways from large storms can cause rapid and profound changes in the streambed that can contribute to flooding. Wymans Run, a small stream in Cochranton Borough, Crawford County, experienced a large rain event in June 2008 that caused sediment to be deposited at a bridge. A hydrodynamic model, Flow and Sediment Transport and Morphological Evolution of Channels (FaSTMECH), which is incorporated into the U.S. Geological Survey Multi-Dimensional Surface-Water Modeling System (MD_SWMS) was constructed to predict boundary shear stress and velocity in Wymans Run using data from the June 2008 event. Shear stress and velocity values can be used to indicate areas of a stream where sediment, transported downstream, can be deposited on the streambed. Because of the short duration of the June 2008 rain event, streamflow was not directly measured but was estimated using U.S. Army Corps of Engineers one-dimensional Hydrologic Engineering Centers River Analysis System (HEC-RAS). Scenarios to examine possible engineering solutions to decrease the amount of sediment at the bridge, including bridge expansion, channel expansion, and dredging upstream from the bridge, were simulated using the FaSTMECH model. Each scenario was evaluated for potential effects on water-surface elevation, boundary shear stress, and velocity.

Fifty-year flood-inundation maps for Comayagua, Hondura

USGS Publications Warehouse

Kresch, David L.; Mastin, Mark C.; Olsen, T.D.

2002-01-01

After the devastating floods caused by Hurricane Mitch in 1998, maps of the areas and depths of the 50-year-flood inundation at 15 municipalities in Honduras were prepared as a tool for agencies involved in reconstruction and planning. This report, which is one in a series of 15, presents maps of areas in the municipality of Comayagua that would be inundated by 50-year floods on Rio Humuya and Rio Majada. Geographic Information System (GIS) coverages of the flood inundation are available on a computer in the municipality of Comayagua as part of the Municipal GIS project and on the Internet at the Flood Hazard Mapping Web page (http://mitchnts1.cr.usgs.gov/projects/floodhazard.html). These coverages allow users to view the flood inundation in much more detail than is possible using the maps in this report. Water-surface elevations for 50-year-floods on Rio Humuya and Rio Majada at Comayagua were estimated using HEC-RAS, a one-dimensional, steady-flow, step-backwater computer program. The channel and floodplain cross sections used in HEC-RAS were developed from an airborne light-detection-and-ranging (LIDAR) topographic survey of the area. The 50-year-flood discharge for Rio Humuya at Comayagua, 1,400 cubic meters per second, was estimated using a regression equation that relates the 50-year-flood discharge to drainage area and mean annual precipitation. The reasonableness of the regression discharge was evaluated by comparing it with drainage-area-adjusted 50-year-flood discharges estimated for three long-term Rio Humuya stream-gaging stations. The drainage-area-adjusted 50-year-flood discharges estimated from the gage records ranged from 946 to 1,365 cubic meters per second. Because the regression equation discharge agrees closely with the high end of the range of discharges estimated from the gaging-station records, it was used for the hydraulic modeling to ensure that the resulting 50-year-flood water-surface elevations would not be underestimated. The 50-year-flood discharge for Rio Majada at Comayagua (230 cubic meters per second) was estimated using the regression equation because there are no long-term gaging-stations on this river from which to estimate the discharge.

Assessment of Environmental Flows for the Rivers of Western Ganges Delta with Special Reference to Indian Sundarban

NASA Astrophysics Data System (ADS)

Bhadra, T.; Hazra, S.; Ghosh, S.; Barman, B. C.

2016-12-01

The Indian Sundarban, situated on the western tide-dominated part of the Ganges delta was formed by the sedimentation of the Ganges and its tributaries. Freshwater is a scarce resource in the Sundarban though it is traversed by rivers. Most of the rivers of Western Ganges Delta, which used to nourish the Sundarban, have become defunct with the passage of time. To ensure sustainable flow and to enhance the flow-dependent ecosystem services in this region, assessment of environmental flows within the system is required. A pilot assessment of environment flows, supported by IUCN has been carried out in some specific river reaches of Western Ganges Delta under the present study. The holistic Building Block Methodology (BBM) has been modified and used for the assessment of environmental flows. In the modified BBM, three distinctive blocks namely Hydro-Morphology, Ecology and Socio-Economy have been selected and indicators like Ganges Dolphin (Platanista gangetica), Sundari tree (Heritiera fomes) and Hilsa fish (Tenualosa ilisha) etc. have been determined to assess the environmental flows. As the discharge data of the selected rivers are restricted in the public domain, the SWAT model has been run to generate the discharge data of the classified rivers. The Hydraulic model, HEC-RAS has been calibrated in the selected River reaches to assess the habitat availability and its changes for indicator species under different flow condition. The study reveals that River Bhagirathi-Hugli requires 150-427 cumec additional water in monsoon and 850-1127 cumec additional water in post-monsoon months for Hilsa migration, whereas 327-486 cumec additional water in pre-monsoon and dry season and 227-386 cumec additional water in post-monsoon months are required for Dolphin movement. Flow requirement of river Ichhamati has also been estimated under the present study. The total required flow for the Sundarban ecosystem to reduce the salinity level from 30ppt to 14ppt during the dry and pre-monsoon months has been estimated as 1700 cumec. The pilot study observes that the present level of flow in the river systems is inadequate to sustain the ecosystem function and the in-stream flow requirement is more than the presently available flow. Keyword: Building Block Methodology, Environmental Flows, HEC-RAS, Indian Sundarban, SWAT.

Comparative evaluation of 1D and quasi-2D hydraulic models based on benchmark and real-world applications for uncertainty assessment in flood mapping

NASA Astrophysics Data System (ADS)

Dimitriadis, Panayiotis; Tegos, Aristoteles; Oikonomou, Athanasios; Pagana, Vassiliki; Koukouvinos, Antonios; Mamassis, Nikos; Koutsoyiannis, Demetris; Efstratiadis, Andreas

2016-03-01

One-dimensional and quasi-two-dimensional hydraulic freeware models (HEC-RAS, LISFLOOD-FP and FLO-2d) are widely used for flood inundation mapping. These models are tested on a benchmark test with a mixed rectangular-triangular channel cross section. Using a Monte-Carlo approach, we employ extended sensitivity analysis by simultaneously varying the input discharge, longitudinal and lateral gradients and roughness coefficients, as well as the grid cell size. Based on statistical analysis of three output variables of interest, i.e. water depths at the inflow and outflow locations and total flood volume, we investigate the uncertainty enclosed in different model configurations and flow conditions, without the influence of errors and other assumptions on topography, channel geometry and boundary conditions. Moreover, we estimate the uncertainty associated to each input variable and we compare it to the overall one. The outcomes of the benchmark analysis are further highlighted by applying the three models to real-world flood propagation problems, in the context of two challenging case studies in Greece.

Hydrologic Simulation in Mediterranean flood prone Watersheds using high-resolution quality data

NASA Astrophysics Data System (ADS)

Eirini Vozinaki, Anthi; Alexakis, Dimitrios; Pappa, Polixeni; Tsanis, Ioannis

2015-04-01

Flooding is a significant threat causing lots of inconveniencies in several societies, worldwide. The fact that the climatic change is already happening, increases the flooding risk, which is no longer a substantial menace to several societies and their economies. The improvement of spatial-resolution and accuracy of the topography and land use data due to remote sensing techniques could provide integrated flood inundation simulations. In this work hydrological analysis of several historic flood events in Mediterranean flood prone watersheds (island of Crete/Greece) takes place. Satellite images of high resolution are elaborated. A very high resolution (VHR) digital elevation model (DEM) is produced from a GeoEye-1 0.5-m-resolution satellite stereo pair and is used for floodplain management and mapping applications such as watershed delineation and river cross-section extraction. Sophisticated classification algorithms are implemented for improving Land Use/ Land Cover maps accuracy. In addition, soil maps are updated with means of Radar satellite images. The above high-resolution data are innovatively used to simulate and validate several historical flood events in Mediterranean watersheds, which have experienced severe flooding in the past. The hydrologic/hydraulic models used for flood inundation simulation in this work are HEC-HMS and HEC-RAS. The Natural Resource Conservation Service (NRCS) curve number (CN) approach is implemented to account for the effect of LULC and soil on the hydrologic response of the catchment. The use of high resolution data provides detailed validation results and results of high precision, accordingly. Furthermore, the meteorological forecasting data, which are also combined to the simulation model results, manage the development of an integrated flood forecasting and early warning system tool, which is capable of confronting or even preventing this imminent risk. The research reported in this paper was fully supported by the "ARISTEIA II" Action ("REINFORCE" program) of the "Operational Education and Life Long Learning programme" and is co-funded by the European Social Fund (ESF) and National Resources.

Determination of Flood Reduction Alternatives for Climate Change Adaptation in Gyeongancheon basin

NASA Astrophysics Data System (ADS)

Han, D.; Joo, H. J.; Jung, J.; Kim, H. S.

2017-12-01

Recently, the frequency of extreme rainfall event has increased due to the climate change and the impermeable area in an urban watershed has also increased due to the rapid urbanization. Therefore, the flood risk is increasing and we ought to prepare countermeasures for flood damage reduction. For the determination of appropriate measures or alternatives, firstly, this study estimated the frequency based rainfall considering the climate change according to the each target period(reference : 1971˜2010, Target period Ⅰ : 2011˜2040, Target period Ⅱ : 2041˜2070, Target period Ⅲ : 2071˜2100). Then the future flood discharge was computed by using HEC-HMS model. We set 5 sizes of drainage pumps and detention ponds respectively as the flood reduction alternatives and the flood level in the river was obtained by each alternative through HEC-RAS model. The flood inundation map was constructed using topographical data and flood water level in the river and the economic analysis was conducted for the flood damage reduction studies using Multi Dimensional Flood Damage Analysis (MD-FDA) tool. As a result of the effectiveness analysis of the flood reduction alternatives, the flood level by drainage pump was reduced by 0.06m up to 0.44m while it was reduced by 0.01m up to 1.86m in the case of the detention pond. The flooded area was shrunk by up to 32.64% from 0.3% and inundation depth was also dropped. As a result of a comparison of the Benefit/Cost ratio estimated by the economic analysis, a detention pond E in the target period Ⅰ and the pump D in the periods Ⅱ and Ⅲ were considered as the appropriate alternatives for the flood damage reduction under the climate change. AcknowledgementsThis research was supported by Basic Science Research Program through the National Research Foundation of Korea(NRF) funded by the Ministry of Science, ICT & Future Planning(2017R1A2B3005695)

Helmet Exhalation Capture System (HECS) Sizing Evaluation for an Advanced Space Suit Portable Life Support System

NASA Technical Reports Server (NTRS)

Paul, Heather L.; Waguespack, Glenn M.; Paul, Thomas H.; Conger, Bruce C.

2008-01-01

As part of NASA s initiative to develop an advanced portable life support system (PLSS), a baseline schematic has been chosen that includes gaseous oxygen in a closed circuit ventilation configuration. Supply oxygen enters the suit at the back of the helmet and return gases pass over the astronaut s body to be extracted at the astronaut s wrists and ankles through the liquid cooling and ventilation garment (LCVG). The extracted gases are then treated using a rapid cycling amine (RCA) system for carbon dioxide and water removal and activated carbon for trace gas removal before being mixed with makeup oxygen and reintroduced into the helmet. Thermal control is provided by a suit water membrane evaporator (SWME). As an extension of the original schematic development, NASA evaluated several Helmet Exhalation Capture System (HECS) configurations as alternatives to the baseline. The HECS configurations incorporate the use of full contact masks or non-contact masks to reduce flow requirements within the PLSS ventilation subsystem. The primary scope of this study was to compare the alternatives based on mass and volume considerations; however other design issues were also briefly investigated. This paper summarizes the results of this sizing analysis task.

Hydrological Modeling of Storm Water Drainage System due to Frequent and Intense Precipitation of Dhaka city using Storm Water Management Model (SWMM)

NASA Astrophysics Data System (ADS)

Hossain, S., Jr.

2015-12-01

Rainfall induced flooding during rainy season is a regular phenomenon in Dhaka City. Almost every year a significant part of the city suffers badly with drainage congestion. There are some highly dense areas with lower ground elevation which submerge under water even with an intense precipitation of few hours. The higher areas also suffer with the drainage problem due to inadequate maintenance of the system and encroachment or illegal filling up of the drainage canals and lakes. Most part of the city suffered from long term urban flooding during historical extreme rainfall events in September 2004, 2007 and July 2009. The situation is likely to worsen in the future due to Climate Change, which may lead to more frequent and intense precipitation. To assess the major and minor drainage systems and elements of the urban basins using the hydrodynamic modelling and, through this, identifying the flooding events and areas, taking into account the current situation and future flood or drainage scenarios. Stormwater modeling has a major role in preventing issues such as flash floods and urban water-quality problems. Stormwater models of a lowered spatial resolution would thus appear valuable if only their ability to provide realistic results could be proved. The present scenario of urban morphology of Dhaka city and existing drainage system is complex for hydrological and hydrodynamic modeling. Furthermore limitations of background data and uncertain future urban scenarios may confine the potential outputs of a model. Although several studies were carried out including modeling for drainage master planning, a detail model for whole DAP (Detaile Area Plan) of Dhaka city area is not available. The model developed under this study is covering the existing drainage system in the study area as well as natural flows in the fringe area. A good number of models are available for hydrological and hydraulic analysis of urban areas. These are MIKE 11, MOUSE, HEC-RAS, HEC HMS and EPA SWMM. EPA-SWMM is used for the study area which is mostly developed and consists pipe networks, open channels and water bodies. This study proposes a methodology for rapid catchment delineation and stormwater management model (SWMM) set-up in a large urban area with model calibration and validation.

Adsorption and Exchange Dynamics in Aging Hydroxyethylcellulose Layers on Silica.

PubMed

Mubarekyan; Santore

2000-07-15

The adsorption kinetics of hydroxyethylcellulose (HEC) on silica and relaxations in adsorbed HEC layers were probed using total internal reflectance fluorescence and near-Brewster reflectivity. Like many random-coil polymers, HEC was found to adsorb at the transport-limited rate. Relaxations occurred at nearly constant interfacial mass when HEC layers were exposed to aqueous solvent, causing the subsequent exchange of chains between the layer and the free solution to become increasingly hindered. Eventually, on the time scale of a day, layers became immobilized and unable to accommodate chains from free solution. A continued fluorescence decay, beyond time scales that could be probed with self exchange, suggested further relaxations of the adsorbed HEC. The polydisperse HEC system (with an average molecular weight near 450,000) behaved qualitatively similar to molecular weight standard polyethylene oxide (PEO) layers on silica. For instance, relaxations in PEO layers occurred on a time scale of 10-20 h, like the HEC layers. Young layers of the latter, however, exhibited self-exchange kinetics that were an order of magnitude slower than PEO layers of similar age. This difference in adsorbed layer dynamics was attributed to HEC's stiffer backbone, compared with flexible PEO. Copyright 2000 Academic Press.

A preliminary comparison of hydrodynamic approaches for flood inundation modeling of urban areas in Jakarta Ciliwung river basin

NASA Astrophysics Data System (ADS)

Rojali, Aditia; Budiaji, Abdul Somat; Pribadi, Yudhistira Satya; Fatria, Dita; Hadi, Tri Wahyu

2017-07-01

This paper addresses on the numerical modeling approaches for flood inundation in urban areas. Decisive strategy to choose between 1D, 2D or even a hybrid 1D-2D model is more than important to optimize flood inundation analyses. To find cost effective yet robust and accurate model has been our priority and motivation in the absence of available High Performance Computing facilities. The application of 1D, 1D/2D and full 2D modeling approach to river flood study in Jakarta Ciliwung river basin, and a comparison of approaches benchmarked for the inundation study are presented. This study demonstrate the successful use of 1D/2D and 2D system to model Jakarta Ciliwung river basin in terms of inundation results and computational aspect. The findings of the study provide an interesting comparison between modeling approaches, HEC-RAS 1D, 1D-2D, 2D, and ANUGA when benchmarked to the Manggarai water level measurement.

Thermal and Hydraulic Conditions Supporting the Recruitment of Asian Carp in Seiche Affected Rivers of Lake Erie Basin - A Case Study of the Lower Sandusky River in Ohio

NASA Astrophysics Data System (ADS)

Soong, D. T.; Santacruz, S.; Jones, L.; Garcia, T.; Kočovský, P. M.; Embke, H.

2017-12-01

Grass Carp Ctenopharyngodon idella (Cyprinidae) is an invasive fish species that spawns in rivers during high-flow events. In their native range, it is believed eggs must hatch within the riverine environment in order to eventually result in production of adult fish. The lower Sandusky River is approximately 26 km long extending from its confluence with Sandusky Bay upstream to the Ballville Dam, which is impassible for Grass Carp. Grass Carp are known to have spawned in the Sandusky River, a tributary to Lake Erie, in 2011, 2013, 2015, and 2017. This study characterizes the thermal and hydraulic conditions under which these eggs could hatch in the lower Sandusky River, a relatively short river reach for egg hatching. Grass Carp eggs collected in 2015 were previously analyzed for hatching locations using a one-dimensional steady-state HEC-RAS hydraulic model. In this study we refine estimates of hatching locations by incorporating the influence of fluctuating water levels downstream due to seiches in Lake Erie and overland and tributary inflows using an unsteady 1D/2D HEC-RAS hydraulic model. Additionally, conditions conducive to successful hatching, which occurs when eggs reach the hatching stage within the river, were analyzed from nine high-flow events between 2011 and 2015. Simulated hydraulic and water temperature data were used as inputs to the Fluvial Egg Drift Simulator (FluEgg) model, which was used to analyze the transport and dispersal of Grass carp eggs until hatching. We will describe the differences in steady- and unsteady-state hydraulic modeling in predicting hatching locations of Grass Carp eggs for the 2015 spawning events. Results will also include hydraulic and temperature variables that contribute to the successful/unsuccessful in-river hatching for the nine flow events simulated.

Sele coastal plain flood risk due to wave storm and river flow interaction

NASA Astrophysics Data System (ADS)

Benassai, Guido; Aucelli, Pietro; Di Paola, Gianluigi; Della Morte, Renata; Cozzolino, Luca; Rizzo, Angela

2016-04-01

Wind waves, elevated water levels and river discharge can cause flooding in low-lying coastal areas, where the water level is the interaction between wave storm elevated water levels and river flow interaction. The factors driving the potential flood risk include weather conditions, river water stage and storm surge. These data are required to obtain inputs to run the hydrological model used to evaluate the water surface level during ordinary and extreme events regarding both the fluvial overflow and storm surge at the river mouth. In this paper we studied the interaction between the sea level variation and the river hydraulics in order to assess the location of the river floods in the Sele coastal plain. The wave data were acquired from the wave buoy of Ponza, while the water level data needed to assess the sea level variation were recorded by the tide gauge of Salerno. The water stages, river discharges and rating curves for Sele river were provided by Italian Hydrographic Service (Servizio Idrografico e Mareografico Nazionale, SIMN).We used the dataset of Albanella station (40°29'34.30"N, 15°00'44.30"E), located around 7 km from the river mouth. The extreme river discharges were evaluated through the Weibull equation, which were associated with their return period (TR). The steady state river water levels were evaluated through HEC-RAS 4.0 model, developed by Hydrologic Engineering Center (HEC) of the United States Army Corps of Engineers Hydrologic Engineering Center (USACE,2006). It is a well-known 1D model that computes water surface elevation (WSE) and velocity at discrete cross-sections by solving continuity, energy and flow resistance (e.g., Manning) equation. Data requirements for HEC-RAS include topographic information in the form of a series of cross-sections, friction parameter in the form of Manning's n values across each cross-section, and flow data including flow rates, flow change locations, and boundary conditions. For a steady state sub-critical simulation, the boundary condition is a known downstream WSE, in this case the elevated water level due to wave setup, wind setup and inverted barometer, while the upstream boundary condition consisted in WSE corresponding to river discharges associated to different return periods. The results of the simulations evidence, for the last 10 kilometers of the river, the burst of critical inundation scenarios even with moderate flow discharge, if associated with concurrent storm surge which increase the water level at the river mouth, obstructing normal flow discharge.

Analysis of the transport of sediment by the Suncook River in Epsom, Pembroke, and Allenstown, New Hampshire, after the May 2006 flood

USGS Publications Warehouse

Flynn, Robert H.

2011-01-01

During May 13-16, 2006, rainfall in excess of 8.8 inches flooded central and southern New Hampshire. On May 15, 2006, a breach in a bank of the Suncook River in Epsom, New Hampshire, caused the river to follow a new path. In order to assess and predict the effect of the sediment in, and the subsequent flooding on, the river and flood plain, a study by the U.S. Geological Survey (USGS) characterizing sediment transport in the Suncook River was undertaken in cooperation with the Federal Emergency Management Agency (FEMA) and the New Hampshire Department of Environmental Services (NHDES). The U.S. Army Corps of Engineers (USACE) Hydrologic Engineering Center-River Analysis System (HEC-RAS) model was used to simulate flow and the transport of noncohesive sediments in the Suncook River from the upstream corporate limit of Epsom to the river's confluence with the Merrimack River in the Village of Suncook (Allenstown and Pembroke, N.H.), a distance of approximately 16 miles. In addition to determining total sediment loads, analyses in this study reflect flooding potentials for selected recurrence intervals that are based on the Suncook River streamgage flow data (streamgage 01089500) and on streambed elevations predicted by HEC-RAS for the end of water year 2010 (September 30, 2010) in the communities of Epsom, Pembroke, and Allenstown. This report presents changes in streambed and water-surface elevations predicted by the HEC-RAS model using data through the end of water year 2010 for the 50-, 10-, 2-, 1-, 0.2-percent annual exceedence probabilities (2-, 10-, 50-, 100-, and 500-year recurrence-interval floods, respectively), calculated daily and annual total sediment loads, and a determination of aggrading and degrading stream reaches. The model was calibrated and evaluated for a 400-day span from May 8, 2008 through June 11, 2009; these two dates coincided with field collection of stream cross-sectional elevation data. Seven sediment-transport functions were evaluated in the model with the Laursen (Copeland) sediment-transport function best describing the sediment load, transport behavior, and changes in streambed elevation for the specified spatial and temporal conditions of the 400-day calibration period. Simulation results from the model and field-collected sediment data indicate that, downstream of the avulsion channel, for the average daily mean flow during the study period, approximately 100 to 400 tons per day of sediment (varying with daily mean flow) was moving past the Short Falls Road Bridge over the Suncook River in Epsom, while approximately 0.05 to 0.5 tons per day of sediment was moving past the Route 28 bridge in Pembroke and Allenstown, and approximately 1 to 10 tons per day was moving past the Route 3 bridge in Pembroke and Allenstown. Changes in water-surface elevation that the model predicted for the end of water year 2010 to be a result of changes in streambed elevation ranged from a mean increase of 0.20 feet (ft) for the 50-percent annual exceedence-probability flood (2-year recurrence-interval flood) due to an average thalweg increase of 0.88 ft between the Short Falls Road Bridge and the Buck Street Dams in Pembroke and Allenstown to a mean decrease of 0.41 ft for the 50-percent annual exceedence-probability flood due to an average thalweg decrease of 0.49 ft above the avulsion in Epsom. An analysis of shear stress (force created by a fluid acting on sediment particles) was undertaken to determine potential areas of erosion and deposition. Based on the median grain size (d50) and shear stress analysis, the study found that in general, for floods greater than the 50-percent annual exceedence probability flood, the shear stress in the streambed is greater than the critical shear stress in much of the river study reach. The result is an expectation of streambed-sediment movement and erosion even at high exceedence-probability events, pending although the stream ultimately attains equilibrium through stream-stabilization measures or the adjustment of the river over time. The potential for aggradation in the Suncook River is greatest in the reach downstream of the avulsion. Specifically, these reaches are (1) downstream of the former sand pit from adjacent to Round Pond to downstream of the flood chute at the large meander bends, and (2) downstream of the Short Falls Road Bridge to approximately 3,800 ft upstream of the Route 28 bridge. The potential for degradation-net lowering of the streambed-is greatest for the reach upstream of the avulsion to the Route 4 bridge.

Assessing the Impacts of Flooding Caused by Extreme Rainfall Events Through a Combined Geospatial and Numerical Modeling Approach

NASA Astrophysics Data System (ADS)

Santillan, J. R.; Amora, A. M.; Makinano-Santillan, M.; Marqueso, J. T.; Cutamora, L. C.; Serviano, J. L.; Makinano, R. M.

2016-06-01

In this paper, we present a combined geospatial and two dimensional (2D) flood modeling approach to assess the impacts of flooding due to extreme rainfall events. We developed and implemented this approach to the Tago River Basin in the province of Surigao del Sur in Mindanao, Philippines, an area which suffered great damage due to flooding caused by Tropical Storms Lingling and Jangmi in the year 2014. The geospatial component of the approach involves extraction of several layers of information such as detailed topography/terrain, man-made features (buildings, roads, bridges) from 1-m spatial resolution LiDAR Digital Surface and Terrain Models (DTM/DSMs), and recent land-cover from Landsat 7 ETM+ and Landsat 8 OLI images. We then used these layers as inputs in developing a Hydrologic Engineering Center Hydrologic Modeling System (HEC HMS)-based hydrologic model, and a hydraulic model based on the 2D module of the latest version of HEC River Analysis System (RAS) to dynamically simulate and map the depth and extent of flooding due to extreme rainfall events. The extreme rainfall events used in the simulation represent 6 hypothetical rainfall events with return periods of 2, 5, 10, 25, 50, and 100 years. For each event, maximum flood depth maps were generated from the simulations, and these maps were further transformed into hazard maps by categorizing the flood depth into low, medium and high hazard levels. Using both the flood hazard maps and the layers of information extracted from remotely-sensed datasets in spatial overlay analysis, we were then able to estimate and assess the impacts of these flooding events to buildings, roads, bridges and landcover. Results of the assessments revealed increase in number of buildings, roads and bridges; and increase in areas of land-cover exposed to various flood hazards as rainfall events become more extreme. The wealth of information generated from the flood impact assessment using the approach can be very useful to the local government units and the concerned communities within Tago River Basin as an aid in determining in an advance manner all those infrastructures (buildings, roads and bridges) and land-cover that can be affected by different extreme rainfall event flood scenarios.

SAM 2.1—A computer program for plotting and formatting surveying data for estimating peak discharges by the slope-area method

USGS Publications Warehouse

Hortness, J.E.

2004-01-01

The U.S. Geological Survey (USGS) measures discharge in streams using several methods. However, measurement of peak discharges is often impossible or impractical due to difficult access, inherent danger of making measurements during flood events, and timing often associated with flood events. Thus, many peak discharge values often are calculated after the fact by use of indirect methods. The most common indirect method for estimating peak dis- charges in streams is the slope-area method. This, like other indirect methods, requires measuring the flood profile through detailed surveys. Processing the survey data for efficient entry into computer streamflow models can be time demanding; SAM 2.1 is a program designed to expedite that process. The SAM 2.1 computer program is designed to be run in the field on a portable computer. The program processes digital surveying data obtained from an electronic surveying instrument during slope- area measurements. After all measurements have been completed, the program generates files to be input into the SAC (Slope-Area Computation program; Fulford, 1994) or HEC-RAS (Hydrologic Engineering Center-River Analysis System; Brunner, 2001) computer streamflow models so that an estimate of the peak discharge can be calculated.

MOLAR: Modular Linux and Adaptive Runtime Support for HEC OS/R Research

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

Frank Mueller

2009-02-05

MOLAR is a multi-institution research effort that concentrates on adaptive, reliable,and efficient operating and runtime system solutions for ultra-scale high-end scientific computing on the next generation of supercomputers. This research addresses the challenges outlined by the FAST-OS - forum to address scalable technology for runtime and operating systems --- and HECRTF --- high-end computing revitalization task force --- activities by providing a modular Linux and adaptable runtime support for high-end computing operating and runtime systems. The MOLAR research has the following goals to address these issues. (1) Create a modular and configurable Linux system that allows customized changes based onmore » the requirements of the applications, runtime systems, and cluster management software. (2) Build runtime systems that leverage the OS modularity and configurability to improve efficiency, reliability, scalability, ease-of-use, and provide support to legacy and promising programming models. (3) Advance computer reliability, availability and serviceability (RAS) management systems to work cooperatively with the OS/R to identify and preemptively resolve system issues. (4) Explore the use of advanced monitoring and adaptation to improve application performance and predictability of system interruptions. The overall goal of the research conducted at NCSU is to develop scalable algorithms for high-availability without single points of failure and without single points of control.« less

Fifty-year flood-inundation maps for La Lima, Honduras

USGS Publications Warehouse

Mastin, Mark C.; Olsen, T.D.

2002-01-01

After the devastating floods caused by Hurricane Mitch in 1998, maps of the areas and depths of the 50-year-flood inundation at 15 municipalities in Honduras were prepared as a tool for agencies involved in reconstruction and planning. This report, which is one in a series of 15, presents maps of areas in the municipality of La Lima that would be inundated by Rio Chamelecon with a discharge of 500 cubic meters per second, the approximate capacity of the river channel through the city of La Lima. The 50-year flood (2,400 cubic meters per second), the original design flow to be mapped, would inundate the entire area surveyed for this municipality. Because water-surface elevations of the 50-year flood could not be mapped properly without substantially expanding the area of the survey, the available data were used instead to estimate the channel capacity of Rio Chamelecon in La Lima by trial-and-error runs of different flows in a numerical model and to estimate the increase in height of levees needed to contain flows of 1,000 and 2,400 cubic meters per second. Geographic Information System (GIS) coverages of the flood inundation are available on a computer in the municipality of La Lima as part of the Municipal GIS project and on the Internet at the Flood Hazard Mapping Web page (http://mitchnts1.cr.usgs.gov/projects/floodhazard.html). These coverages allow users to view the flood inundation in much more detail than is possible using the maps in this report. Water-surface elevations for various discharges on Rio Chamelecon at La Lima were determined using HEC-RAS, a one-dimensional, steady-flow, step-backwater computer program. The channel and floodplain cross sections used in HEC-RAS were developed from an airborne light-detection-and-ranging (LIDAR) topographic survey of the area and ground surveys at three bridges. Top-of-levee or top-of-channel-bank elevations and locations at the cross sections were critical to estimating the channel capacity of Rio Chamelecon. These elevations and locations are provided along with the water-surface elevations for the 500-cubic-meter-per-second flow of Rio Chamelecon. Also, water-surface elevations of the 1,000 and 2,400 cubic-meter-per-second flows are provided, assuming that the existing levees are raised to contained the flows.

Plasma ctDNA RAS mutation analysis for the diagnosis and treatment monitoring of metastatic colorectal cancer patients

PubMed Central

Vidal, J; Muinelo, L; Dalmases, A; Jones, F; Edelstein, D; Iglesias, M; Orrillo, M; Abalo, A; Rodríguez, C; Brozos, E; Vidal, Y; Candamio, S; Vázquez, F; Ruiz, J; Guix, M; Visa, L; Sikri, V; Albanell, J; Bellosillo, B; López, R; Montagut, C

2017-01-01

Abstract Background RAS assessment is mandatory for therapy decision in metastatic colorectal cancer (mCRC) patients. This determination is based on tumor tissue, however, genotyping of circulating tumor (ct)DNA offers clear advantages as a minimally invasive method that represents tumor heterogeneity. Our study aims to evaluate the use of ctDNA as an alternative for determining baseline RAS status and subsequent monitoring of RAS mutations during therapy as a component of routine clinical practice. Patients and methods RAS mutational status in plasma was evaluated in mCRC patients by OncoBEAM™ RAS CRC assay. Concordance of results in plasma and tissue was retrospectively evaluated. RAS mutations were also prospectively monitored in longitudinal plasma samples from selected patients. Results Analysis of RAS in tissue and plasma samples from 115 mCRC patients showed a 93% overall agreement. Plasma/tissue RAS discrepancies were mainly explained by spatial and temporal tumor heterogeneity. Analysis of clinico-pathological features showed that the site of metastasis (i.e. peritoneal, lung), the histology of the tumor (i.e. mucinous) and administration of treatment previous to blood collection negatively impacted the detection of RAS in ctDNA. In patients with baseline mutant RAS tumors treated with chemotherapy/antiangiogenic, longitudinal analysis of RAS ctDNA mirrored response to treatment, being an early predictor of response. In patients RAS wt, longitudinal monitoring of RAS ctDNA revealed that OncoBEAM was useful to detect emergence of RAS mutations during anti-EGFR treatment. Conclusion The high overall agreement in RAS mutational assessment between plasma and tissue supports blood-based testing with OncoBEAM™ as a viable alternative for genotyping RAS of mCRC patients in routine clinical practice. Our study describes practical clinico-pathological specifications to optimize RAS ctDNA determination. Moreover, OncoBEAM™ is useful to monitor RAS in patients undergoing systemic therapy to detect resistance and evaluate the efficacy of particular treatments. PMID:28419195

Properties and in vitro drug release of hyaluronic acid-hydroxyethyl cellulose hydrogels for transdermal delivery of isoliquiritigenin.

PubMed

Kong, Bong Ju; Kim, Ayoung; Park, Soo Nam

2016-08-20

In the present study, the properties of hydrogel systems based on hyaluronic acid (HA)-hydroxyethyl cellulose (HEC) were investigated for effective transdermal delivery of isoliquiritigenin (ILTG). Hydrogels were synthesized by chemical cross-linking, and network structures were characterised using scanning electron microscopy (SEM) and surface area analyser. Texture properties and swelling of HA-HEC hydrogels were found to be closely linked to cross-linker concentration and swelling medium. Water in HA-HEC hydrogels was found to exist mostly in the form of free water. The viscoelasticity and the network stabilization of the hydrogels were analysed via rheological studies. The release kinetics of the hydrogel followed Fickian diffusion mechanism. In an in vitro skin penetration study, the system substantially improved the delivery of ILTG into the skin. These results indicate that the hydrogel system composed of HA and HEC has potential as a transdermal delivery system, with cross-linking density and the swelling medium influencing the properties. Copyright © 2016 Elsevier Ltd. All rights reserved.

Comparison of two plethysmography systems in assessment of forearm blood flow.

PubMed

Leslie, Stephen J; Attinà, Teresa; Hultsch, Ellen; Bolscher, Luc; Grossman, Matthias; Denvir, Martin A; Webb, David J

2004-05-01

Venous occlusion plethysmography is widely used to assess forearm blood flow (FBF). We compared the established Hokanson system (HEC4) with a newly developed Filtrass 2001 system (F2001). The HEC4 uses mercury-in-Silastic strain gauges, whereas F2001 detects volume changes with a nonmercury linear displacement device. The aim of this study was to evaluate the new F2001 against the HEC4 in terms of repeatability and systematic bias. Ten subjects were studied on 4 separate days in random order using either the HEC4 on both arms, the F2001 on both arms, the HEC4 on the right arm with the F2001 on the left, or the F2001 on the right arm and the HEC4 on the left. Stroop's colored word conflict test and postocclusive hyperemia were used to increase FBF, and lower body negative pressure was used to lower FBF. Stroop's colored word conflict test and lower body negative pressure increased (24.6 +/- 1.5%, n = 240, P < 0.0001) and decreased (18.7 +/- 0.8%, n = 240, P < 0.0001) FBF, respectively. Postocclusive hyperemia after occlusion times of 5, 8, and 13 min substantially increased FBF by 390 +/- 86, 756 +/- 217, and 851 +/- 132%, respectively. Repeatability was not different between the devices (0.10 +/- 2.37 vs. -0.47 +/- 1.92 l/min, n = 125, P > 0.05), and there was no systematic bias. The F2001 is a newly developed plethysmography system that does not utilize mercury and is suitable for assessing changes of FBF in physiological studies.

[Effect of GPER on the activation of PI3K/Akt induced by 17β-estradiol in endometrial carcinoma cells].

PubMed

Zhang, Yan-Cai; Guo, Rui-Xia; Ge, Xin; Qiao, Yu-Huan

2012-04-01

To investigate the expression of G protein-coupled ER (GPER) and ER in the activation of phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) induced by 17β-estradiol (17β-E(2))in endometrial carcinoma cells, Ishikawa and HEC-1A. Expressions of GPER, ERα and ERβ protein in Ishikawa and HEC-1A cells were detected by immunohistochemical SP method. Levels of GPER, ERα and ERβ were examined by western blot in Ishikawa and HEC-1A cells after treated with 1×10(-6) mol/L 17β-E(2) at different time (0, 15, 30, 60, 120 minutes). GPER was positive expressed in Ishikawa and HEC-1A cells. ERα and ERβ were both positive expressed in Ishikawa cells. While, ERα was weakly expressed and ERβ was almost negatively expressed in HEC-1A cells. Western blot analysis showed that 1×10(-6) mol/L 17β-E(2) treatment, the Ishikawa and HEC-1A cells GPER protein level for 15 minutes markedly increased (P < 0.05), which Ishikawa 30 minutes, when cells reached the highest level (0.192 ± 0.004), HEC-1A cells for 15 minutes and reached the highest level (0.184 ± 0.006); Ishikawa and HEC-1A cells, Akt, activation of 15 minutes from the treatment start was significantly increased (P < 0.05), which Ishikawa cells for 30 minutes and reached the highest level (0.666 ± 0.021), HEC-1A cells for 15 minutes and reached maximum (0.788 ± 0.035); Ishikawa and HEC-1A cells, ERα and ERβ protein expression did not change significantly (P > 0.05). GPER likely involved in non-nuclear activation of PI3K/Akt signaling pathways in endometrial carcinoma cells, Ishikawa and HEC-1A.

Carbohydrate-protein interactions investigated on plastic chips statically coated with hydrophobically modified hydroxyethylcellulose.

PubMed

Dang, Fuquan; Maeda, Eiki; Osafune, Tomo; Nakajima, Kazuki; Kakehi, Kazuaki; Ishikawa, Mitsuru; Baba, Yoshinobu

2009-12-15

We developed a novel method for rapid screening of carbohydrate-protein interactions using poly(methyl methacrylate) (PMMA) channels statically coated with hydrophobically modified hydroxyethylcellulose (HM-HEC). We found that a self-assembled monolayer (SAM) of HM-HEC on a PMMA surface intact by water allows rapid and reproducible separations of glycan samples using a 20 mM phosphate without HM-HEC. The underlying mechanism for dynamic and static coatings on the PMMA surface is discussed. Simultaneous analysis of the molecular interaction between a complex mixture of carbohydrates from alpha1-acid glycoprotein and proteins has been successfully achieved in PMMA channels statically coated with a SAM of HM-HEC.

Hydroxyethyl cellulose hydrogel for wound dressing: Fabrication, characterization and in vitro evaluation.

PubMed

El Fawal, Gomaa F; Abu-Serie, Marwa M; Hassan, Mohamed A; Elnouby, Mohamed S

2018-05-01

In this study, new hydrogel membranes were developed based on hydroxyethyl cellulose (HEC) supplemented with tungsten oxide for further implementing in wound treatment. HEC hydrogel membranes were fabricated and crosslinked using citric acid (CA). Various tests were carried out including FTIR, XRD, porosity measurements, swelling, mechanical properties, gel fraction, and thermal gravimetric analysis to evaluate the efficiency of the prepared membranes as wound dressing material. In addition, wound healing activity of the examined membranes for human dermal fibroblast cell line was investigated employing in vitro scratching model. Furthermore, the potency of the prepared membranes to suppress wound complications was studied via determination of their anti-inflammatory and antibacterial activities exploiting MTT, ELISA, and disk agar diffusion methods. The results demonstrated that the HEC hydrogel membranes revealed an anti-inflammatory and antibacterial efficacy. Moreover, HEC improved the safety of tungsten oxide toward normal human cells (white blood cells and dermal fibroblast). Furthermore, HEC membranes loaded with WO 3 revealed the highest activities against Salmonella sp. pursued by P. aeruginosa in compared with the negative HEC hydrogel membrane. The current approach corroborated that HEC amended by tungsten oxide could be applied as a promising safe candidate for wound dressing material. Copyright © 2018 Elsevier B.V. All rights reserved.

Hemodynamic responses to acute and gradual renal artery stenosis in pigs.

PubMed

Rognant, Nicolas; Rouvière, Olivier; Janier, Marc; Lê, Quoc Hung; Barthez, Paul; Laville, Maurice; Juillard, Laurent

2010-11-01

Reduction of renal blood flow (RBF) due to a renal artery stenosis (RAS) can lead to renal ischemia and atrophy. However in pigs, there are no data describing the relationship between the degree of RAS, the reduction of RBF, and the increase of systemic plasma renin activity (PRA). Therefore, we conducted a study in order to measure the effect of acute and gradual RAS on RBF, mean arterial pressure (MAP), and systemic PRA in pigs. RAS was induced experimentally in six pigs using an occluder placed around the renal artery downstream of an ultrasound flow probe. The vascular occluder was inflated gradually to reduce RBF. At each inflation step, percentage of RAS was measured by digital subtraction angiography (DSA) with simultaneous measurements of RBF, MAP, and PRA. Data were normalized to baseline values obtained before RAS induction. Piecewise regression analysis was performed between percentage of RAS and relative RBF, MAP, and PRA, respectively. In all pigs, the relationship between the degree of RAS and RBF was similar. RBF decreased over a threshold of 42% of RAS, with a rapid drop in RBF when RAS reached 70%. PRA increased dramatically over a threshold of 58% of RAS (+1,300% before occlusion). MAP increased slightly (+15% before occlusion) without identifiable threshold. This study emphasizes that the relation between the degree of RAS and RBF and systemic PRA is not linear and that a high degree of RAS must be reached before the occurrence of significant hemodynamic and humoral effects.

Abiotic controls of emergent macrophyte density in a bedrock channel - The Cahaba River, AL (USA)

NASA Astrophysics Data System (ADS)

Vaughn, Ryan S.; Davis, Lisa

2015-10-01

Research examining bedrock channels is growing. Despite this, biotic-abiotic interactions remain a topic mostly addressed in alluvial systems. This research identified hydrogeomorphic factors operating at the patch-scale (100-102 m) in bedrock shoals of the Cahaba River (AL) that help determine the distribution of the emergent aquatic macrophyte, Justicia americana. Macrophyte patch density (number of stems/m2) and percent bedrock void surface area (rock surface area/m2 occupied by joints, fractures, and potholes) were measured (n = 24 within two bedrock shoals) using stem counts and underwater photography, respectively. One-dimensional hydrologic modeling (HEC-RAS 4.1.0) was completed for a section within a shoal to examine velocity and channel depth as controlling variables for macrophyte patch density. Results from binary logistic regression analysis identified depth and velocity as good predictors of the presence or absence of Justicia americana within shoal structures (depth p = 0.001, velocity p = 0.007), which is a similar finding to previous research conducted in alluvial systems. Correlation analysis between bedrock surface void area and stem density demonstrated a statistically significant positive correlation (r = 0.665, p = 0.01), elucidating a link between abiotic-biotic processes that may well be unique to bedrock channels. These results suggest that the amount of void space present in bedrock surfaces, in addition to localized depth and velocity, helps control macrophyte patch density in bedrock shoal complexes. The utility of geomorphology in explaining patch-scale habitat heterogeneity in this study highlights geomorphology's potential to help understand macrophyte habitat heterogeneity at the reach scale, while also demonstrating its promise for mapping and understanding habitat heterogeneity at the system scale.

Ngas Multi-Stage Coaxial High Efficiency Cooler (hec)

NASA Astrophysics Data System (ADS)

Nguyen, T.; Toma, G.; Jaco, C.; Raab, J.

2010-04-01

This paper presents the performance data of the single and two-stage High Efficiency Cooler (HEC) tested with coaxial cold heads. The single stage coaxial cold head has been optimized to operate at temperatures of 40 K and above. The two-stage parallel cold head configuration has been optimized to operate at 30 K and above and provides a long-life, low mass and efficient two-stage version of the Northrop Grumman Aerospace Systems (NGAS) flight qualified single stage HEC cooler. The HEC pulse tube cryocoolers are the latest generation of flight coolers with heritage to the 12 Northrop Grumman Aerospace Systems (NGAS) coolers currently on orbit with 2 operating for more than 11.5 years. This paper presents the performance data of the one and two-stage versions of this cooler under a wide range of heat rejection temperature, cold head temperature and input power.

Hydrologic, Hydraulic, and Flood Analyses of the Blackberry Creek Watershed, Kendall County, Illinois

USGS Publications Warehouse

Murphy, Elizabeth A.; Straub, Timothy D.; Soong, David T.; Hamblen, Christopher S.

2007-01-01

Results of the hydrologic model, flood-frequency, hydraulic model, and flood-hazard analysis of the Blackberry Creek watershed in Kendall County, Illinois, indicate that the 100-year and 500-year flood plains cover approximately 3,699 and 3,762 acres of land, respectively. On the basis of land-cover data for 2003, most of the land in the flood plains was cropland and residential land. Although many acres of residential land were included in the flood plain, this land was mostly lawns, with 25 homes within the 100-year flood plain, and 41 homes within the 500-year flood plain in the 2003 aerial photograph. This report describes the data collection activities to refine the hydrologic and hydraulic models used in an earlier study of the Kane County part of the Blackberry Creek watershed and to extend the flood-frequency analysis through water year 2003. The results of the flood-hazard analysis are presented in graphical and tabular form. The hydrologic model, Hydrological Simulation Program - FORTRAN (HSPF), was used to simulate continuous water movement through various land-use patterns in the watershed. Flood-frequency analysis was applied to an annual maximum series to determine flood quantiles in subbasins for flood-hazard analysis. The Hydrologic Engineering Center- River Analysis System (HEC-RAS) hydraulic model was used to determine the 100-year and 500-year flood elevations, and the 100-year floodway. The hydraulic model was calibrated and verified using observations during three storms at two crest-stage gages and the U.S. Geological Survey streamflowgaging station near Yorkville. Digital maps of the 100-year and 500-year flood plains and the 100-year floodway for each tributary and the main stem of Blackberry Creek were compiled.

High-End Computing Challenges in Aerospace Design and Engineering

NASA Technical Reports Server (NTRS)

Bailey, F. Ronald

2004-01-01

High-End Computing (HEC) has had significant impact on aerospace design and engineering and is poised to make even more in the future. In this paper we describe four aerospace design and engineering challenges: Digital Flight, Launch Simulation, Rocket Fuel System and Digital Astronaut. The paper discusses modeling capabilities needed for each challenge and presents projections of future near and far-term HEC computing requirements. NASA's HEC Project Columbia is described and programming strategies presented that are necessary to achieve high real performance.

Freedom space for rivers: An economically viable river management concept in a changing climate

NASA Astrophysics Data System (ADS)

Buffin-Bélanger, Thomas; Biron, Pascale M.; Larocque, Marie; Demers, Sylvio; Olsen, Taylor; Choné, Guénolé; Ouellet, Marie-Audray; Cloutier, Claude-André; Desjarlais, Claude; Eyquem, Joanna

2015-12-01

The freedom space concept applies hydrogeomorphic principles to delineate zones that are either frequently flooded or actively eroding, or that include riparian wetlands. Freedom space limits mapped for three rivers in southern Quebec (Canada) were assessed to determine whether they would still be valid under a future climate using a sensitivity analysis approach with numerical models predicting mobility of meanders (RVRMeander) and flood stage (HEC-RAS). The freedom space limits were also used in a cost-benefit analysis over a 50-year period where costs consist of loss or limitations to the right of farming and construction in this zone, whereas benefits are avoided costs for existing or future bank stabilization structures and avoided costs of flooding in agricultural areas. The economic value of ecosystem services provided by riparian wetlands and increased buffer zones within the freedom space were also included in the analysis. Results show that freedom space limits would be robust in future climate, and show net present values ranging from CDN0.7 to 3.7 million for the three rivers, with ratios of benefits over costs ranging between 1.5:1 and 4.8:1. River management based on freedom space is thus beneficial for society over a 50-year period.

Creating a Flood Risk Index to Improve Community Resilience

NASA Astrophysics Data System (ADS)

Klima, K.; El Gammal, L.

2017-12-01

While flood risk reduction is an existent discourse and agenda in policy and insurance, vulnerabilities vary between communities; some communities may have aging infrastructure, or an older/poorer population less able to absorb a flood, putting them at increased risk from the hazards. As a result, some are considering environmental justice aspects of flood risk reduction. To date, catastrophe models have focused on creating floodmaps (e.g., NOAA's Sea Level Rise Viewer, Climate Central's Surging Seas), or on linking hydrological models to economic loss models (e.g., HEC-RAS + HAZUS). However, this approach may be highly inequitable between areas of different income (as well as other demographics). Some have begun work on combining hydrology with vulnerability information (e.g., USACE's North Atlantic Comprehensive Coastal Study). To our knowledge, no one has tried to adapt the more advanced known heat risk theory to water risk by combining hydrology information (e.g., HEC-RAS, floodplain maps) with the social vulnerability (e.g., Cutter et al.) of the residents. This project will create a method to combine water hazard data with a derived water vulnerability index to help a community understand their current and future water risk. We will use the case study area of Pittsburgh, PA, which faces severe precipitation and riverine flooding hazards. Building on present literature of factors influencing water vulnerability contextualized to the Pittsburgh region, we will identify, quantify, and map the top factors impacting water vulnerability. We will combine these with flood maps to identify the geospatial distribution of water risk. This work will allow policy makers to identify location-specific aspects of water vulnerability and risk in any community, thus promoting environmental justice. It is possible that this type of original research would create maps of relative water risk that may prove as understandable to the general public as other flood maps, and may also help to promote "just resilience". This presentation will present a method to combine water hazard data with a derived water vulnerability index to present work on the geospatial distribution of water risk in Pittsburgh, PA.

Comparison of 2D numerical models for river flood hazard assessment: simulation of the Secchia River flood in January, 2014

NASA Astrophysics Data System (ADS)

Shustikova, Iuliia; Domeneghetti, Alessio; Neal, Jeffrey; Bates, Paul; Castellarin, Attilio

2017-04-01

Hydrodynamic modeling of inundation events still brings a large array of uncertainties. This effect is especially evident in the models run for geographically large areas. Recent studies suggest using fully two-dimensional (2D) models with high resolution in order to avoid uncertainties and limitations coming from the incorrect interpretation of flood dynamics and an unrealistic reproduction of the terrain topography. This, however, affects the computational efficiency increasing the running time and hardware demands. Concerning this point, our study evaluates and compares numerical models of different complexity by testing them on a flood event that occurred in the basin of the Secchia River, Northern Italy, on 19th January, 2014. The event was characterized by a levee breach and consequent flooding of over 75 km2 of the plain behind the dike within 48 hours causing population displacement, one death and economic losses in excess of 400 million Euro. We test the well-established TELEMAC 2D, and LISFLOOD-FP codes, together with the recently launched HEC-RAS 5.0.3 (2D model), all models are implemented using different grid size (2-200 m) based on the 1 m digital elevation model resolution. TELEMAC is a fully 2D hydrodynamic model which is based on the finite-element or finite-volume approach. Whereas HEC-RAS 5.0.3 and LISFLOOD-FP are both coupled 1D-2D models. All models are calibrated against observed inundation extent and maximum water depths, which are retrieved from remotely sensed data and field survey reports. Our study quantitatively compares the three modeling strategies highlighting differences in terms of the ease of implementation, accuracy of representation of hydraulic processes within floodplains and computational efficiency. Additionally, we look into the different grid resolutions in terms of the results accuracy and computation time. Our study is a preliminary assessment that focuses on smaller areas in order to identify potential modeling schemes that would be efficient for simulating flooding scenarios for large and very large floodplains. This research aims at contributing to the reduction of uncertainties and limitations in hazard and risk assessment.

Design of cellulose ether-based macromolecular prodrugs of ciprofloxacin for extended release and enhanced bioavailability.

PubMed

Amin, Muhammad; Abbas, Nazia Shahana; Hussain, Muhammad Ajaz; Sher, Muhammad; Edgar, Kevin J

2018-07-01

The present study reveals the syntheses of hydroxypropylcellulose‑(HPC) and hydroxyethylcellulose‑(HEC) based macromolecular prodrugs (MPDs) of ciprofloxacin (CIP) using homogeneous reaction methodology. Covalently loaded drug content (DC) of each prodrug was quantified using UV-Vis spectrophotometry to determine degree of substitution (DS). HPC-ciprofloxacin (HPC-CIP) conjugates showed DS of CIP in the range 0.87-1.15 whereas HEC-ciprofloxacin (HEC-CIP) conjugates showed DS range 0.51-0.75. Transmission electron microscopy revealed that HPC-CIP conjugate 2 and HEC-CIP conjugate 6 self-assembled into nanoparticles of 150-300 and 180-250nm, respectively. Size exclusion chromatography revealed HPC-CIP conjugate 2 and HEC-CIP conjugate 6 as monodisperse systems. In vitro drug release studies indicated 15 and 43% CIP release from HPC-CIP conjugate 2 after 6h in simulated gastric and simulated intestinal fluids (SGF and SIF), respectively. HEC-CIP conjugate 6 showed 16% and 46% release after 6h in SGF and SIF, respectively. HPC-CIP conjugate 2 and HEC-CIP conjugate 6 exhibited half-lives of 10.87 and 11.71h, respectively with area under the curve values of 164 and 175hμgmL -1 , respectively, indicating enhanced bioavailability and improved pharmacokinetic profiles in animal model. Equal antibacterial activities to that of unmodified CIP confirmed their competitive efficacies. Cytotoxicity studies supported their non-toxic nature and biocompatibility. Copyright © 2018 Elsevier B.V. All rights reserved.

Preparation and characterization of poly(acrylic acid)-hydroxyethyl cellulose graft copolymer.

PubMed

Abdel-Halim, E S

2012-10-01

Poly(acrylic acid) hydroxyethyl cellulose [poly(AA)-HEC] graft copolymer was prepared by polymerizing acrylic acid (AA) with hydroxyethyl cellulose (HEC) using potassium bromate/thiourea dioxide (KBrO(3)/TUD) as redox initiation system. The polymerization reaction was carried out under a variety of conditions including concentrations of AA, KBrO(3) and TUD, material to liquor ratio and polymerization temperature. The polymerization reaction was monitored by withdrawing samples from the reaction medium and measuring the total conversion. The rheological properties of the poly(AA)-HEC graft copolymer were investigated. The total conversion and rheological properties of the graft copolymer depended on the ratio of KBrO(3) to TUD and on acrylic acid concentration as well as temperature and material to liquor ratio. Optimum conditions of the graft copolymer preparation were 30 mmol KBrO(3) and 30 mmol TUD/100g HEC, 100% AA (based on weight of HEC), duration 2h at temperature 50 °C using a material to liquor ratio of 1:10. Copyright © 2012. Published by Elsevier Ltd.

Graphene-oxide stabilization in electrolyte solutions using hydroxyethyl cellulose for drug delivery application.

PubMed

Mianehrow, Hanieh; Moghadam, Mohamad Hasan Mohamadzadeh; Sharif, Farhad; Mazinani, Saeedeh

2015-04-30

Stabilization of graphene oxide (GO) in physiological solution is performed using hydroxyethyl cellulose (HEC) to make the resultant nanohybrid suitable for targeted drug delivery purposes. Short and long term stability of GO suspensions with different ionic strengths were assessed using ultraviolet-visible spectroscopy (UV-vis), atomic force microscopy (AFM) and zeta potential measurements. Results depicted that HEC effectively stabilized GO in electrolyte solutions and the mechanism of stabilization appeares to be depended on HEC content. Drug loading and release behavior of folic acid (FA) as a model drug, from GO-HEC nanohybrid were studied to assess its application in drug delivery systems. Results showed the nanohybrid could be highly loaded by folic acid. Moreover, HEC content in the nanohybrid played an important role in final application to make it applicable either as a carrier for controllable drug release or as a folate-targeted drug carrier. In addition, according to cytotoxicity results, the nanohybrid showed good biocompatibility which indeed confirms its potential application as a drug carrier. Copyright © 2015 Elsevier B.V. All rights reserved.

Slow-release granisetron (APF530) versus palonosetron for chemotherapy-induced nausea/vomiting: analysis by American Society of Clinical Oncology emetogenicity criteria.

PubMed

Raftopoulos, Harry; Boccia, Ralph; Cooper, William; O'Boyle, Erin; Gralla, Richard J

2015-09-01

APF530 is a novel sustained-release formulation of granisetron. In a Phase III trial, APF530 500 mg was noninferior to palonosetron 0.25 mg in preventing acute chemotherapy-induced nausea and vomiting (CINV) after moderately (MEC) or highly emetogenic chemotherapy (HEC) and delayed CINV after MEC, but not superior in preventing delayed CINV after HEC. Emetogenicity was classified by Hesketh criteria; this reanalysis uses newer American Society of Clinical Oncology criteria. Complete responses (no emesis or rescue medication) after cycle one were reanalyzed after reclassification of MEC and HEC by American Society of Clinical Oncology criteria. APF530 maintained noninferiority to palonosetron. Single-dose APF530 is a promising alternative to palonosetron for preventing acute and delayed CINV after MEC or HEC. The Clinicaltrials.gov identifier for this study is NCT00343460.

The Impact of Renin-Angiotensin System Blockade on Renal Outcomes and Mortality in Pre-Dialysis Patients with Advanced Chronic Kidney Disease.

PubMed

Oh, Yun Jung; Kim, Sun Moon; Shin, Byung Chul; Kim, Hyun Lee; Chung, Jong Hoon; Kim, Ae Jin; Ro, Han; Chang, Jae Hyun; Lee, Hyun Hee; Chung, Wookyung; Lee, Chungsik; Jung, Ji Yong

2017-01-01

Renin-angiotensin-system (RAS) blockade is thought to slow renal progression in patients with chronic kidney disease (CKD). However, it remains uncertain if the habitual use of RAS inhibitors affects renal progression and outcomes in pre-dialysis patients with advanced CKD. In this multicenter retrospective cohort study, we identified 2,076 pre-dialysis patients with advanced CKD (stage 4 or 5) from a total of 33,722 CKD patients. RAS blockade users were paired with non-users for analyses using inverse probability of treatment-weighted (IPTW) and propensity score (PS) matching. The outcomes were renal death, all-cause mortality, hospitalization for hyperkalemia, and interactive factors as composite outcomes. RAS blockade users showed an increased risk of renal death in PS-matched analysis (hazard ratio [HR], 1.381; 95% CI, 1.071-1.781; P = 0.013), which was in agreement with the results of IPTW analysis (HR, 1.298; 95% CI, 1.123-1.500; P < 0.001). The risk of composite outcomes was higher in RAS blockade users in IPTW (HR, 1.154; 95% CI, 1.016-1.310; P = 0.027), but was marginal significance in PS matched analysis (HR, 1.243; 95% CI, 0.996-1.550; P = 0.054). The habitual use of RAS blockades in pre-dialysis patients with advanced CKD may have a detrimental effect on renal outcome without improving all-cause mortality. Further studies are warranted to determine whether withholding RAS blockade may lead to better outcomes in these patients.

An Undergraduate Research Experience Studying Ras and Ras Mutants

ERIC Educational Resources Information Center

Griffeth, Nancy; Batista, Naralys; Grosso, Terri; Arianna, Gianluca; Bhatia, Ravnit; Boukerche, Faiza; Crispi, Nicholas; Fuller, Neno; Gauza, Piotr; Kingsbury, Lyle; Krynski, Kamil; Levine, Alina; Ma, Rui Yan; Nam, Jennifer; Pearl, Eitan; Rosa, Alessandro; Salarbux, Stephanie; Sun, Dylan

2016-01-01

Each January from 2010 to 2014, an undergraduate workshop on modeling biological systems was held at Lehman College of the City University of New York. The workshops were funded by a National Science Foundation (NSF) Expedition in Computing, "Computational Modeling and Analysis of Complex Systems (CMACS)." The primary goal was to…

Applications of ASFCM(Assessment System of Flood Control Measurement) in Typhoon Committee Members

NASA Astrophysics Data System (ADS)

Kim, C.

2013-12-01

Due to extreme weather environment such as global warming and greenhouse effect, the risks of having flood damage has been increased with larger scale of flood damages. Therefore, it became necessary to consider modifying climate change, flood damage and its scale to the previous dimension measurement evaluation system. In this regard, it is needed to establish a comprehensive and integrated system to evaluate the most optimized measures for flood control through eliminating uncertainties of socio-economic impacts. Assessment System of Structural Flood Control Measures (ASFCM) was developed for determining investment priorities of the flood control measures and establishing the social infrastructure projects. ASFCM consists of three modules: 1) the initial setup and inputs module, 2) the flood and damage estimation module, and 3) the socio-economic analysis module. First, we have to construct the D/B for flood damage estimation, which is the initial and input data about the estimation unit, property, historical flood damages, and applied area's topographic & hydrological data. After that, it is important to classify local characteristic for constructing flood damage data. Five local characteristics (big city, medium size city, small city, farming area, and mountain area) are classified by criterion of application (population density). Next step is the floodplain simulation with HEC-RAS which is selected to simulate inundation. Through inputting the D/B and damage estimation, it is able to estimate the total damage (only direct damage) that is the amount of cost to recover the socio-economic activities back to the safe level before flood did occur. The last module suggests the economic analysis index (B/C ratio) with Multidimensional Flood Damage Analysis. Consequently, ASFCM suggests the reference index in constructing flood control measures and planning non-structural systems to reduce water-related damage. It is possible to encourage flood control planners and managers to consider and apply the socio-economic analysis results. ASFCM was applied in Republic of Korea, Thailand and Philippines to review efficiency and applicability. Figure 1. ASFCM Application(An-yang Stream, Republic of Korea)

Impact of the Columbia Supercomputer on NASA Space and Exploration Mission

NASA Technical Reports Server (NTRS)

Biswas, Rupak; Kwak, Dochan; Kiris, Cetin; Lawrence, Scott

2006-01-01

NASA's 10,240-processor Columbia supercomputer gained worldwide recognition in 2004 for increasing the space agency's computing capability ten-fold, and enabling U.S. scientists and engineers to perform significant, breakthrough simulations. Columbia has amply demonstrated its capability to accelerate NASA's key missions, including space operations, exploration systems, science, and aeronautics. Columbia is part of an integrated high-end computing (HEC) environment comprised of massive storage and archive systems, high-speed networking, high-fidelity modeling and simulation tools, application performance optimization, and advanced data analysis and visualization. In this paper, we illustrate the impact Columbia is having on NASA's numerous space and exploration applications, such as the development of the Crew Exploration and Launch Vehicles (CEV/CLV), effects of long-duration human presence in space, and damage assessment and repair recommendations for remaining shuttle flights. We conclude by discussing HEC challenges that must be overcome to solve space-related science problems in the future.

Systemic Regulation of RAS/MAPK Signaling by the Serotonin Metabolite 5-HIAA.

PubMed

Schmid, Tobias; Snoek, L Basten; Fröhli, Erika; van der Bent, M Leontien; Kammenga, Jan; Hajnal, Alex

2015-05-01

Human cancer is caused by the interplay of mutations in oncogenes and tumor suppressor genes and inherited variations in cancer susceptibility genes. While many of the tumor initiating mutations are well characterized, the effect of genetic background variation on disease onset and progression is less understood. We have used C. elegans genetics to identify genetic modifiers of the oncogenic RAS/MAPK signaling pathway. Quantitative trait locus analysis of two highly diverged C. elegans isolates combined with allele swapping experiments identified the polymorphic monoamine oxidase A (MAOA) gene amx-2 as a negative regulator of RAS/MAPK signaling. We further show that the serotonin metabolite 5-hydroxyindoleacetic acid (5-HIAA), which is a product of MAOA catalysis, systemically inhibits RAS/MAPK signaling in different organs of C. elegans. Thus, MAOA activity sets a global threshold for MAPK activation by controlling 5-HIAA levels. To our knowledge, 5-HIAA is the first endogenous small molecule that acts as a systemic inhibitor of RAS/MAPK signaling.

Granisetron Extended-Release Injection: A Review in Chemotherapy-Induced Nausea and Vomiting.

PubMed

Deeks, Emma D

2016-12-01

An extended-release (ER) subcutaneously injectable formulation of the first-generation 5-HT 3 receptor antagonist granisetron is now available in the USA (Sustol ® ), where it is indicated for the prevention of acute and delayed chemotherapy-induced nausea and vomiting (CINV) following moderately emetogenic chemotherapy (MEC) or anthracycline and cyclophosphamide combination chemotherapy regimens in adults. Granisetron ER is administered as a single subcutaneous injection and uses an erosion-controlled drug-delivery system to allow prolonged granisetron release. Primary endpoint data from phase III studies after an initial cycle of chemotherapy indicate that, when used as part of an antiemetic regimen, granisetron ER injection is more effective than intravenous ondansetron in preventing delayed CINV following highly emetogenic chemotherapy (HEC); is noninferior to intravenous palonosetron in preventing both acute CINV following MEC or HEC and delayed CINV following MEC; and is similar, but not superior, to palonosetron in preventing delayed CINV following HEC. The benefits of granisetron ER were seen in various patient subgroups, including those receiving anthracycline plus cyclophosphamide-based HEC, and (in an extension of one of the studies) over multiple MEC or HEC cycles. Granisetron ER injection is generally well tolerated, with an adverse event profile similar to that of ondansetron or palonosetron. Thus, granisetron ER injection expands the options for preventing both acute and delayed CINV in adults with cancer receiving MEC or anthracycline plus cyclophosphamide-based HEC.

Thiolated hydroxyethylcellulose: synthesis and in vitro evaluation.

PubMed

Sarti, Federica; Staaf, Alexander; Sakloetsakun, Duangkamon; Bernkop-Schnürch, Andreas

2010-11-01

In recent years, thiomers have received considerable interest due to advantageous characteristics, such as improved mucoadhesive and permeation enhancing properties. Thiolated polymers, however, are characterized by an ionic charge which represents for various applications a great limitation. The aim of this study was therefore to synthesize a novel thiolated polymer not exhibiting ionizable groups. Hydroxyethylcellulose (HEC) was chosen as polymer backbone. The chemical modification was achieved by the replacement of hydroxyl groups on the carbohydrate structure with thiol moieties, using thiourea as thiolating reagent. The resulting thiolated hydroxyethylcellulose (HEC-SH) was characterized in vitro regarding its gelling properties, swelling behaviour, mucoadhesion on freshly excised porcine intestinal mucosa and permeation enhancing effect across rat intestinal mucosa. The new thiomer displayed up to 131.58 ± 11.17 μmol thiol groups per gram polymer, which are responsible for the observed in situ gelling capacity. The swelling behaviour and the mucoadhesive properties of tablets based on HEC-SH were 1.5-fold and 4-fold improved compared with unmodified HEC, respectively. The permeation enhancing effect of 0.5% (m/v) HEC-SH on rhodamine 123 (Rho-123) transport was 1.9-fold improved compared with buffer only. According to these results, HEC-SH seems to represent a promising tool for the development of in situ gelling, mucoadhesive delivery systems with permeation enhancing properties. Copyright © 2010 Elsevier B.V. All rights reserved.

Predicting the occurrence of channelized debris flow by an integrated cascading model: A case study of a small debris flow-prone catchment in Zhejiang Province, China

NASA Astrophysics Data System (ADS)

Wei, Zhen-lei; Xu, Yue-Ping; Sun, Hong-yue; Xie, Wei; Wu, Gang

2018-05-01

Excessive water in a channel is an important factor that triggers channelized debris flows. Floods and debris flows often occur in a cascading manner, and thus, calculating the amount of runoff accurately is important for predicting the occurrence of debris flows. In order to explore the runoff-rainfall relationship, we placed two measuring facilities at the outlet of a small, debris flow-prone headwater catchment to explore the hydrological response of the catchment. The runoff responses generally consisted of a rapid increase in runoff followed by a slower decrease. The peak runoff often occurred after the rainfall ended. The runoff discharge data were simulated by two different modeling approaches, i.e., the NAM model and the Hydrologic Engineering Center-Hydrologic Modeling System (HEC-HMS) model. The results showed that the NAM model performed better than the HEC-HMS model. The NAM model provided acceptable simulations, while the HEC-HMS model did not. Then, we coupled the calculated results of the NAM model with an empirically based debris flow initiation model to obtain a new integrated cascading disaster modeling system to provide improved disaster preparedness and hazard management. In this case study, we found that the coupled model could correctly predict the occurrence of debris flows. Furthermore, we evaluated the effect of the range of input parameter values on the hydrographical shape of the runoff. We also used the grey relational analysis to conduct a sensitivity analysis of the parameters of the model. This study highlighted the important connections between rainfall, hydrological processes, and debris flow, and it provides a useful prototype model system for operational forecasting of debris flows.

Assessing potential removal of low-head dams in urban settings: an example from the Ottawa River, NW Ohio.

PubMed

Roberts, Sheila J; Gottgens, Johan F; Spongberg, Alison L; Evans, James E; Levine, Norman S

2007-01-01

This is a study of the scientific component of an effort to restore an urban river by removing a low-head dam. The Secor Dam is owned by a local government entity near Toledo, Ohio. The proposed removal of the last structure impeding flow on the Ottawa River has broad appeal, but the owner is concerned about liability issues, particularly potential changes to the flood regime, the presence of contaminated sediments behind the dam, and possible downstream transport of reservoir sediments. Assessing sediment contamination involved sediment sampling and analysis of trace metals and organic contaminants. Forecasting sediment transport involved field methods to determine the volume and textural properties of reservoir and upstream sediment and calculations to determine the fate of reservoir sediments. Forecasting changes in the flood regime involved HEC-RAS hydrological models to determine before and after dam removal flood scenarios using LiDAR data imported into an ArcGIS database. The resulting assessment found potential sediment contamination to be minor, and modeling showed that the removal of the dam would have minimal impacts on sediment transport and flood hazards. Based on the assessment, the removal of the dam has been approved by its owners.

Flood evolution assessment and monitoring using hydrological modelling techniques: analysis of the inundation areas at a regional scale

NASA Astrophysics Data System (ADS)

Podhoranyi, M.; Kuchar, S.; Portero, A.

2016-08-01

The primary objective of this study is to present techniques that cover usage of a hydrodynamic model as the main tool for monitoring and assessment of flood events while focusing on modelling of inundation areas. We analyzed the 2010 flood event (14th May - 20th May) that occurred in the Moravian-Silesian region (Czech Republic). Under investigation were four main catchments: Opava, Odra, Olše and Ostravice. Four hydrodynamic models were created and implemented into the Floreon+ platform in order to map inundation areas that arose during the flood event. In order to study the dynamics of the water, we applied an unsteady flow simulation for the entire area (HEC-RAS 4.1). The inundation areas were monitored, evaluated and recorded semi-automatically by means of the Floreon+ platform. We focused on information about the extent and presence of the flood areas. The modeled flooded areas were verified by comparing them with real data from different sources (official reports, aerial photos and hydrological networks). The study confirmed that hydrodynamic modeling is a very useful tool for mapping and monitoring of inundation areas. Overall, our models detected 48 inundation areas during the 2010 flood event.

Performance Analysis of AeroRP with Ground Station Advertisements

DTIC Science & Technology

2012-03-12

results showed that AeroRP outperforms the traditional MANET routing protocols in terms of throughput and packet delivery ra - tio (PDR) [5, 6]. AeroRP...and waiting for the source to re- send the packet increases the end-to-end delay. The AeroNP corruption indicator and HEC -CRC (header error check...Dev ID | NP HEC CRC-16 | +-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+-+ \\ \\ / AeroTP Payload

Flood extent and water level estimation from SAR using data-model integration

NASA Astrophysics Data System (ADS)

Ajadi, O. A.; Meyer, F. J.

2017-12-01

Synthetic Aperture Radar (SAR) images have long been recognized as a valuable data source for flood mapping. Compared to other sources, SAR's weather and illumination independence and large area coverage at high spatial resolution supports reliable, frequent, and detailed observations of developing flood events. Accordingly, SAR has the potential to greatly aid in the near real-time monitoring of natural hazards, such as flood detection, if combined with automated image processing. This research works towards increasing the reliability and temporal sampling of SAR-derived flood hazard information by integrating information from multiple SAR sensors and SAR modalities (images and Interferometric SAR (InSAR) coherence) and by combining SAR-derived change detection information with hydrologic and hydraulic flood forecast models. First, the combination of multi-temporal SAR intensity images and coherence information for generating flood extent maps is introduced. The application of least-squares estimation integrates flood information from multiple SAR sensors, thus increasing the temporal sampling. SAR-based flood extent information will be combined with a Digital Elevation Model (DEM) to reduce false alarms and to estimate water depth and flood volume. The SAR-based flood extent map is assimilated into the Hydrologic Engineering Center River Analysis System (Hec-RAS) model to aid in hydraulic model calibration. The developed technology is improving the accuracy of flood information by exploiting information from data and models. It also provides enhanced flood information to decision-makers supporting the response to flood extent and improving emergency relief efforts.

Translating and culturally adapting the shortened version of the Hospital Ethical Climate Survey (HECS-S) - retaining or modifying validated instruments.

PubMed

Pergert, Pernilla; Bartholdson, Cecilia; Wenemark, Marika; Lützén, Kim; Af Sandeberg, Margareta

2018-05-10

The Hospital Ethical Climate Survey (HECS) was developed in the USA and later shortened (HECS-S). HECS has previously been translated into Swedish and the aim of this study was to describe a process of translating and culturally adapting HECS-S and to develop a Swedish multi-professional version, relevant for paediatrics. Another aim was to describe decisions about retaining versus modifying the questionnaire in order to keep the Swedish version as close as possible to the original while achieving a good functional level and trustworthiness. In HECS-S, the respondents are asked to indicate the veracity of statements. In HECS and HECS-S the labels of the scale range from 'almost never true' to 'almost always true'; while the Swedish HECS labels range from 'never' to 'always'. The procedure of translating and culturally adapting the Swedish version followed the scientific structure of guidelines. Three focus group interviews and three cognitive interviews were conducted with healthcare professionals. Furthermore, descriptive data were used from a previous study with healthcare professionals (n = 89), employing a modified Swedish HECS. Decisions on retaining or modifying items were made in a review group. The Swedish HECS-S consists of 21 items including all 14 items from HECS-S and items added to develop a multi-professional version, relevant for paediatrics. The descriptive data showed that few respondents selected 'never' and 'always'. To obtain a more even distribution of responses and keep Swedish HECS-S close to HECS-S, the original labels were retained. Linguistic adjustments were made to retain the intended meaning of the original items. The word 'respect' was used in HECS-S with two different meanings and was replaced in one of these because participants were concerned that respecting patients' wishes implied always complying with them. The process of developing a Swedish HECS-S included decisions on whether to retain or modify. Only minor adjustments were needed to achieve a good functional level and trustworthiness although some items needed to be added. Adjustments made could be used to also improve the English HECS-S. The results shed further light on the need to continuously evaluate even validated instruments and adapt them before use.

Varying effects of geomorphic change on floodplain inundation and forest communities

NASA Astrophysics Data System (ADS)

Keim, R.; Johnson, E. L.; Edwards, B. L.; King, S. L.; Hupp, C. R.

2015-12-01

Overbank flooding in floodplains is an important control on vegetation, but effects of changing flooding are difficult to predict because sensitivities of plant communities to multidimensional flooding (frequency, depth, duration, and timing) are not well understood. We used HEC-RAS to model the changing flooding regime in the lower White River floodplain, Arkansas, in response to rapid incision of the Mississippi River in the 1930s, and quantified flood frequency, depth, and duration by forest community type. Incision has decreased flooding especially in terms of frequency, which is one of the most important variables for ecological processes. Modeled depth-duration curves varied more among floodplain reaches than among forest communities within the same reach, but forest communities are now arranged in accordance with new flood regimes in place after river incision. Forest responses to subtle geomorphic change are slower than other vegetation communities, so detection of the full ramifications of ecohydrologic change may require decades.

A simulation for the gated weir opening of Wonokromo River, Rungkut District, Surabaya

NASA Astrophysics Data System (ADS)

Handajani, N.; Wahjudijanto, I.; Mu'afi, M.

2018-01-01

The gated weir is a weir that the crest elevation could be operated based on the flow through the river. The upstream water level of the gated weir could be controlled with gate opening or closing. This study applied a simulation with HEC-RAS 4,0 program in order to know the river hydraulic condition after the gated weir has built. According to the rainfall intensity from each sub-watershed, Distribution Log Pearson III with return period 50 years (Q50) was determined to calculate the design flood discharge. By using Rational Method, the design flood discharge is 470 m3/s. The Results show that capacity of the river is able to accomodate Q50 with discharge 470 m3/s and the gate should be fully opened during flood. This condition could passed the normal discharge at + 5.00 m elevation.

Oil-in-Water Emulsions Stabilized by Saponified Epoxidized Soybean Oil-Grafted Hydroxyethyl Cellulose.

PubMed

Huang, Xujuan; Li, Qiaoguang; Liu, He; Shang, Shibin; Shen, Minggui; Song, Jie

2017-05-03

An oil-in-water emulsion stabilized by saponified epoxidized soybean oil-grafted hydroxyethyl cellulose (H-ESO-HEC) was investigated. By using an ultrasonic method, oil-in-water emulsions were prepared by blending 50 wt % soybean oil and 50 wt % H-ESO-HEC aqueous suspensions. The influence of H-ESO-HEC concentrations on the properties of oil-in-water emulsions was examined. The H-ESO-HEC concentrations in the aqueous phase varied from 0.02 to 0.40 wt %. When the H-ESO-HEC concentration was 0.4 wt %, the emulsion remained stable for >80 days. The mean droplet sizes of the emulsions decreased by increasing the H-ESO-HEC concentration and extending the ultrasonic time. The adsorption amounts of H-ESO-HEC at the oil-water interface increased when the H-ESO-HEC concentrations in the aqueous phase increased. The rheological property revealed that the apparent viscosity of the H-ESO-HEC-stabilized oil-in-water emulsions increased when the H-ESO-HEC concentrations increased. Steady flow curves indicated an interfacial film formation in the emulsions. The evolution of G', G″, and tan η indicated the predominantly elastic behaviors of all the emulsions.

Evaluation of sub daily satellite rainfall estimates through flash flood modelling in the Lower Middle Zambezi Basin

NASA Astrophysics Data System (ADS)

Matingo, Thomas; Gumindoga, Webster; Makurira, Hodson

2018-05-01

Flash floods are experienced almost annually in the ungauged Mbire District of the Middle Zambezi Basin. Studies related to hydrological modelling (rainfall-runoff) and flood forecasting require major inputs such as precipitation which, due to shortage of observed data, are increasingly using indirect methods for estimating precipitation. This study therefore evaluated performance of CMORPH and TRMM satellite rainfall estimates (SREs) for 30 min, 1 h, 3 h and daily intensities through hydrologic and flash flood modelling in the Lower Middle Zambezi Basin for the period 2013-2016. On a daily timestep, uncorrected CMORPH and TRMM show Probability of Detection (POD) of 61 and 59 %, respectively, when compared to rain gauge observations. The best performance using Correlation Coefficient (CC) was 70 and 60 % on daily timesteps for CMORPH and TRMM, respectively. The best RMSE for CMORPH was 0.81 % for 30 min timestep and for TRMM was 2, 11 % on 3 h timestep. For the year 2014 to 2015, the HEC-HMS (Hydrological Engineering Centre-Hydrological Modelling System) daily model calibration Nash Sutcliffe efficiency (NSE) for Musengezi sub catchment was 59 % whilst for Angwa it was 55 %. Angwa sub-catchment daily NSE results for the period 2015-2016 was 61 %. HEC-RAS flash flood modeling at 100, 50 and 25 year return periods for Angwa sub catchment, inundated 811 and 867 ha for TRMM rainfall simulated discharge at 3 h and daily timesteps, respectively. For CMORPH generated rainfall, the inundation was 818, 876, 890 and 891 ha at daily, 3 h, 1 h and 30 min timesteps. The 30 min time step for CMORPH effectively captures flash floods with the measure of agreement between simulated flood extent and ground control points of 69 %. For TRMM, the 3 h timestep effectively captures flash floods with coefficient of 67 %. The study therefore concludes that satellite products are most effective in capturing localized hydrological processes such as flash floods for sub-daily rainfall, because of improved spatial and temporal resolution.

Development of Probabilistic Flood Inundation Mapping For Flooding Induced by Dam Failure

NASA Astrophysics Data System (ADS)

Tsai, C.; Yeh, J. J. J.

2017-12-01

A primary function of flood inundation mapping is to forecast flood hazards and assess potential losses. However, uncertainties limit the reliability of inundation hazard assessments. Major sources of uncertainty should be taken into consideration by an optimal flood management strategy. This study focuses on the 20km reach downstream of the Shihmen Reservoir in Taiwan. A dam failure induced flood herein provides the upstream boundary conditions of flood routing. The two major sources of uncertainty that are considered in the hydraulic model and the flood inundation mapping herein are uncertainties in the dam break model and uncertainty of the roughness coefficient. The perturbance moment method is applied to a dam break model and the hydro system model to develop probabilistic flood inundation mapping. Various numbers of uncertain variables can be considered in these models and the variability of outputs can be quantified. The probabilistic flood inundation mapping for dam break induced floods can be developed with consideration of the variability of output using a commonly used HEC-RAS model. Different probabilistic flood inundation mappings are discussed and compared. Probabilistic flood inundation mappings are hoped to provide new physical insights in support of the evaluation of concerning reservoir flooded areas.

Validation of methods to control for immortal time bias in a pharmacoepidemiologic analysis of renin-angiotensin system inhibitors in type 2 diabetes.

PubMed

Yang, Xilin; Kong, Alice Ps; Luk, Andrea Oy; Ozaki, Risa; Ko, Gary Tc; Ma, Ronald Cw; Chan, Juliana Cn; So, Wing Yee

2014-01-01

Pharmacoepidemiologic analysis can confirm whether drug efficacy in a randomized controlled trial (RCT) translates to effectiveness in real settings. We examined methods used to control for immortal time bias in an analysis of renin-angiotensin system (RAS) inhibitors as the reference cardioprotective drug. We analyzed data from 3928 patients with type 2 diabetes who were recruited into the Hong Kong Diabetes Registry between 1996 and 2005 and followed up to July 30, 2005. Different Cox models were used to obtain hazard ratios (HRs) for cardiovascular disease (CVD) associated with RAS inhibitors. These HRs were then compared to the HR of 0.92 reported in a recent meta-analysis of RCTs. During a median follow-up period of 5.45 years, 7.23% (n = 284) patients developed CVD and 38.7% (n = 1519) were started on RAS inhibitors, with 39.1% of immortal time among the users. In multivariable analysis, time-dependent drug-exposure Cox models and Cox models that moved immortal time from users to nonusers both severely inflated the HR, and time-fixed models that included immortal time deflated the HR. Use of time-fixed Cox models that excluded immortal time resulted in a HR of only 0.89 (95% CI, 0.68-1.17) for CVD associated with RAS inhibitors, which is closer to the values reported in RCTs. In pharmacoepidemiologic analysis, time-dependent drug exposure models and models that move immortal time from users to nonusers may introduce substantial bias in investigations of the effects of RAS inhibitors on CVD in type 2 diabetes.

The effect of renin-angiotensin system inhibitors on mortality and heart failure hospitalization in patients with heart failure and preserved ejection fraction: a systematic review and meta-analysis.

PubMed

Shah, Ravi V; Desai, Akshay S; Givertz, Michael M

2010-03-01

Although renin-angiotensin system (RAS) inhibitors have little demonstrable effect on mortality in patients with heart failure and preserved ejection fraction (HF-PEF), some trials have suggested a benefit with regard to reduction in HF hospitalization. Here, we systematically review and evaluate prospective clinical studies of RAS inhibitors enrolling patients with HF-PEF, including the 3 major trials of RAS inhibition (Candesartan in Patients with Chronic Heart Failure and Preserved Left Ventricular Ejection Fraction [CHARM-Preserved], Irbesartan in Patients with Heart Failure and Preserved Ejection Fraction [I-PRESERVE], and Perindopril in Elderly People with Chronic Heart Failure [PEP-CHF]). We also conducted a pooled analysis of 8021 patients in the 3 major randomized trials of RAS inhibition in HF-PEF (CHARM-Preserved, I-PRESERVE, and PEP-CHF) in fixed-effect models, finding no clear benefit with regard to all-cause mortality (odds ratio [OR] 1.03, 95% confidence interval [CI], 0.92-1.15; P=.62), or HF hospitalization (OR 0.90, 95% CI 0.80-1.02; P=.09). Although RAS inhibition may be valuable in the management of comorbidities related to HF-PEF, RAS inhibition in HF-PEF is not associated with consistent reduction in HF hospitalization or mortality in this emerging cohort. Copyright (c) 2010 Elsevier Inc. All rights reserved.

Flood risk assessment through 1D/2D couple HEC-RAS hydrodynamic modeling- A case study of Surat City, Lower Tapi Basin, India

NASA Astrophysics Data System (ADS)

Patel, Dhruvesh; Ramirez, Jorge; Srivastava, Prashant; Bray, Michaela; Han, Dawei

2017-04-01

Surat, known as the diamond city of Gujart is situated 100 km downstream of Ukai dam and near the mouth of river Tapi and affected by the flood at every alternate year. The city experienced catastrophic floods in 1933, 1959, 1968, 1970, 1994, 1998 and 2006. It is estimated that a single flood event during August 6-12, 2006 in Surat and Hazira twin-city, caused heavy damages, resulted in the death of 300 people and property damage worth € 289 million. The peak discharge of 25768 m3 s-1 release from Ukai dam was responsible for the disastrous flood in Surat city. To identifylow lying areas prone to inundation and reduce the uncertainty in flood mitigation measures, HEC-RAS based 1D/2D Couple hydrodynamic modeling is carried out for Surat city. Release from the Ukai dam and tidal level of the sea are considered for upstream and downstream boundary condition. 299 surveyed cross-sections have been considered for 1D modeling, whereas a topographic map at 0.5 m contour interval was used to produce a 5 m grid and SRTM (30 & 90 m) grid has been considered for Suart and Lower Tapi Basin (LTB). Flow is simulated under unsteady conditions, calibrated for the year 1998 and validated for the year 2006. The simulated result shows that the 9th August 18.00 hr was the worst day for Surat city and maximum 75-77 % area was under inundation. Most of the flooded area experienced 0.25 m/s water velocity with the duration of 90 hr. Due to low velocity and high duration of the flood, a low lying area within the west zone and south-west zone of the city was badly affected by the flood, whereas the south zone and south-east zone was least. Simulated results show good correlation when compared with an observed flood level map. The simulated results will be helpful to improve the flood resilience strategy at Surat city and reduce the uncertainty for flood inundation mapping for future dam releases. The present case study shows the applicability of 1D/2D coupled hydrodynamic modeling for flood inundation mapping and can be applied for flood assessment at locations with similar geographical conditions.

Assessment of Hydraulic Conditions Supporting the Recruitment of Asian Carp in the Illinois Waterway - A Case Study Using Known Spawning Events of 2015

NASA Astrophysics Data System (ADS)

Soong, D. T.; Garcia, T.; Duncker, J.; Zhu, Z.; Butler, S.; Diana, M.; Wahl, D.

2016-12-01

The upstream movement of Asian carp in the Illinois Waterway poses a potential threat to the Great Lakes. If established within the Great Lakes, Asian carp may disrupt the food web and harm the ecosystems of the Great Lakes. Understanding the Asian carp reproduction, including the timing and locations of adult spawning and the transport and dispersal of eggs and larvae, is essential information for managing the Asian carp population in the Illinois Waterway. The Fluvial Egg Drift Simulator (FluEgg) model, a Lagrangian particle tracking model, has been used to study the transport and dispersal of eggs and larvae. The FluEgg model inputs are water temperature and hydraulic properties. At present, field measured or modeled hydraulics from steady-state simulations have been used in FluEgg modeling and the applications have shown useful results for evaluating Asian carp reproduction in the Illinois Waterway. However, there is a need to use data based on more representative time-variable hydraulic conditions from spawning to the time larvae reach the Gas Bladder Inflation Stage (GBI). The GBI stage is critical because that is the stage when the young fish seek nursery habitat. In June 2015, Asian carp spawning was observed at two locations along the Illinois Waterway, one below Starved Rock Lock and Dam near Utica, and the one in the La Grange Pool near Havana, Illinois. This study analyzes how hydraulic modeling can improve the predictability of the FluEgg model. An unsteady HEC-RAS hydraulic model of the Illinois Waterway from Brandon Road Lock and Dam to Grafton, Illinois was used to reproduce the June 2015 flood event. Hydraulic data from HEC-RAS modeling, including predicted spatial and temporal discharge, water depth, and shear velocity; and measured water temperature data were used as input to the FluEgg model. FluEgg simulation results illustrate the downstream drifting of eggs and larvae until reaching the GBI stage. These simulation results can be analyzed, along with habitat maps, to evaluate the possibility of successful recruitment and to identify nursery habitats. This presentation communicates the important connections between hydraulic characteristics, thermal conditions, the development of eggs and larvae of Asian carp, and the likelihood of recruitment success.

Evaluating Capability of Devils Lake Emergency Outlets in Lowering Lake Water Levels While Controlling flooding Damage to Downstream

NASA Astrophysics Data System (ADS)

Scanlon, B. R.; Zhang, Z.; Sun, A.; Save, H.; Mueller Schmied, H.; Wada, Y.; Doll, P. M.; Eisner, S.

2016-12-01

Devils Lake is an endorheic lake locate in the Red River of the North Basin with a natural outlet at a level of 444.7 meters above the sea level flowing into the Sheyenne River. Historical accumulation of salts has dramatically increased the concentration of salts in the lake, particularly of the sulfates, that are much greater than the surrounding water bodies. Since 1993, the lake water level has risen by nearly 10 meters and caused extensive flooding in the surrounding area, and greatly increased the chance of natural spillage to the Sheyenne River. To mitigate Devils Lake flooding and to prevent its natural spillage, two outlets were constructed at the west and east sides of the lake to drain the water to the Sheyenne River in a controlled fashion. However, pumping water from Devils Lake has degraded water quality of the Sheyenne River. In an earlier study, we coupled Soil and Water Assessment Tools (SWAT) and CE-QUAL-W2 models to investigate the changes of sulfate distribution as the lake water level rises. We found that, while operating the two outlets has lowered Devils Lake water level by 0.7 meter, it has also significantly impaired the Sheyenne River water quality, increasing the Sheyenne River average sulfate concentration from 105 to 585 mg l-1 from 2012 to 2014 In this study, we investigate the impact of the outlets on the Sheyenne River floodplain by coupling SWAT and HEC-RAS model. The SWAT model performed well in simulating daily streamflow in the Sheyenne River with R2>0.56 and ENS > 0.52. The simulated water depths and floodplain by HEC-RAS model for the Sheyenne River agreed well with observations. Operating the outlets from April to October can draw down the Devil Lake water level by 0.45 m, but the drained water would almost double the extension of the Sheyenne River floodplain and elevate the sulfate concentration in the Sheyenne River above the 450 mg l-1 North Dakota sulfate concentration standard for stream class I. Operating the outlets is a wicked problem solving Devils Lake flooding leads to extra discharge and water quality degradation in the Sheyenne River. Solving this problem requires trade of between Devils Lake flood control and the Sheyenne River water quality preservation.

Evaluating Capability of Devils Lake Emergency Outlets in Lowering Lake Water Levels While Controlling flooding Damage to Downstream

NASA Astrophysics Data System (ADS)

Shabani, A.; Zhang, X.

2017-12-01

Devils Lake is an endorheic lake locate in the Red River of the North Basin with a natural outlet at a level of 444.7 meters above the sea level flowing into the Sheyenne River. Historical accumulation of salts has dramatically increased the concentration of salts in the lake, particularly of the sulfates, that are much greater than the surrounding water bodies. Since 1993, the lake water level has risen by nearly 10 meters and caused extensive flooding in the surrounding area, and greatly increased the chance of natural spillage to the Sheyenne River. To mitigate Devils Lake flooding and to prevent its natural spillage, two outlets were constructed at the west and east sides of the lake to drain the water to the Sheyenne River in a controlled fashion. However, pumping water from Devils Lake has degraded water quality of the Sheyenne River. In an earlier study, we coupled Soil and Water Assessment Tools (SWAT) and CE-QUAL-W2 models to investigate the changes of sulfate distribution as the lake water level rises. We found that, while operating the two outlets has lowered Devils Lake water level by 0.7 meter, it has also significantly impaired the Sheyenne River water quality, increasing the Sheyenne River average sulfate concentration from 105 to 585 mg l-1 from 2012 to 2014 In this study, we investigate the impact of the outlets on the Sheyenne River floodplain by coupling SWAT and HEC-RAS model. The SWAT model performed well in simulating daily streamflow in the Sheyenne River with R2>0.56 and ENS > 0.52. The simulated water depths and floodplain by HEC-RAS model for the Sheyenne River agreed well with observations. Operating the outlets from April to October can draw down the Devil Lake water level by 0.45 m, but the drained water would almost double the extension of the Sheyenne River floodplain and elevate the sulfate concentration in the Sheyenne River above the 450 mg l-1 North Dakota sulfate concentration standard for stream class I. Operating the outlets is a wicked problem solving Devils Lake flooding leads to extra discharge and water quality degradation in the Sheyenne River. Solving this problem requires trade of between Devils Lake flood control and the Sheyenne River water quality preservation.

Chemotherapy-induced nausea and vomiting is less controlled at delayed phase in patients with esophageal cancer: a prospective registration study by the CINV Study Group of Japan.

PubMed

Baba, Yoshifumi; Baba, Hideo; Yamamoto, Sachiko; Shimada, Hideaki; Shibata, Tomotaka; Miyazaki, Tatsuya; Yoshikawa, Takaki; Nakajima, Yasuaki; Tsuji, Yasushi; Shimokawa, Mototsugu; Kitagawa, Yuko; Aiba, Keisuke

2017-02-01

Chemotherapy is an indispensable therapeutic approach for esophageal cancer. Although chemotherapy-induced nausea and vomiting (CINV) is one of the most crucial adverse events, the current state of CINV in patients with esophageal cancer remains unclear. This multicenter prospective observational study analyzed data for 192 patents with esophageal cancer who underwent moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC). The patients recorded their CINV incidence and severity daily for 7 days after receiving chemotherapy, using visual analog scales (VAS). Of the 192 patients, 181 received HEC including cisplatin, and 11 patients received MEC including nedaplatin. Approximately 81% of HEC and 82% of MEC patients received antiemetic therapy in compliance with guidelines. Although CINV was controlled relatively well in the early phase (days 1-4), it was not fully controlled in late phase (days 5-7) for both the HEC and MEC groups. Female sex was a major risk factor for delayed vomiting (P=0.034). Multivariate logistic regression analysis for VAS revealed that motion sickness, age, and use of other antiemetics were risk factors for delayed nausea. Adherence to antiemetic guidelines effectively controls vomiting but is less effective against delayed CINV in both HEC and MEC patients. Identification of individual risk factors, such as female sex, will help develop personalized treatments for CINV. In the clinical setting for esophageal cancer, regimens that include nedaplatin might need to be treated as HEC. © 2016 International Society for Diseases of the Esophagus.

The Intracrine Renin-Angiotensin System

PubMed Central

Kumar, Rajesh; Thomas, Candice M.; Yong, Qian Chen; Chen, Wen; Baker, Kenneth M.

2014-01-01

The renin-angiotensin system (RAS) is one of the earliest and most extensively studied hormonal systems. The RAS is an atypical hormonal system in several ways. The major bioactive peptide of the system, angiotensin (Ang) II, is neither synthesized in, nor targets one specific organ. New research has identified additional peptides with important physiological and pathological roles. More peptides also mean newer enzymatic cascades that generate these peptides and more receptors that mediate the function. In addition, completely different roles of components that constitute the RAS have been uncovered, such as that for prorenin via the prorenin receptor. Complexity of the RAS is further enhanced by the presence of sub-systems in tissues, which act in an autocrine/paracrine manner independent of the endocrine system. The RAS seems relevant at the cellular level, wherein individual cells have a complete system, termed the intracellular RAS. Thus, from cells to tissues to the entire organism, the RAS exhibits continuity while maintaining independent control at different levels. The intracellular RAS is a relatively new concept for the RAS. The current review presents a synopsis of the literature on this system in different tissues. PMID:22590974

Modeling chemical accumulation in sediment of small waterbodies accounting for sediment transport and water-sediment exchange processes over long periods.

PubMed

Patterson, David Albert; Strehmel, Alexander; Erzgräber, Beate; Hammel, Klaus

2017-12-01

In a recent scientific opinion of the European Food Safety Authority it is argued that the accumulation of plant protection products in sediments over long time periods may be an environmentally significant process. Therefore, the European Food Safety Authority proposed a calculation to account for plant protection product accumulation. This calculation, however, considers plant protection product degradation within sediment as the only dissipation route, and does not account for sediment dynamics or back-diffusion into the water column. The hydraulic model Hydrologic Engineering Center-River Analysis System (HEC-RAS; US Army Corps of Engineers) was parameterized to assess sediment transport and deposition dynamics within the FOrum for Co-ordination of pesticide fate models and their USe (FOCUS) scenarios in simulations spanning 20 yr. The results show that only 10 to 50% of incoming sediment would be deposited. The remaining portion of sediment particles is transported across the downstream boundary. For a generic plant protection product substance this resulted in deposition of only 20 to 50% of incoming plant protection product substance. In a separate analysis, the FOCUS TOXSWA model was utilized to examine the relative importance of degradation versus back-diffusion as loss processes from the sediment compartment for a diverse range of generic plant protection products. In simulations spanning 20 yr, it was shown that back-diffusion was generally the dominant dissipation process. The results of the present study show that sediment dynamics and back-diffusion should be considered when calculating long-term plant protection product accumulation in sediment. Neglecting these may lead to a systematic overestimation of accumulation. Environ Toxicol Chem 2017;36:3223-3231. © 2017 SETAC. © 2017 SETAC.

Growth of MCF-7 breast cancer cells and efficacy of anti-angiogenic agents in a hydroxyethyl chitosan/glycidyl methacrylate hydrogel.

PubMed

Wang, Hejing; Qian, Junmin; Zhang, Yaping; Xu, Weijun; Xiao, Juxiang; Suo, Aili

2017-01-01

Breast cancer negatively affects women's health worldwide. The tumour microenvironment plays a critical role in tumour initiation, proliferation, and metastasis. Cancer cells are traditionally grown in two-dimensional (2D) cultures as monolayers on a flat solid surface lacking cell-cell and cell-matrix interactions. These experimental conditions deviate from the clinical situation. Improved experimental systems that can mimic the in vivo situation are required to discover new therapies, particularly for anti-angiogenic agents that mainly target intercellular factors and play an essential role in treating some cancers. Chitosan can be modified to construct three-dimensional (3D) tumour models. Here, we report an in vitro 3D tumour model using a hydroxyethyl chitosan/glycidyl methacrylate (HECS-GMA) hydrogel produced by a series of chitosan modifications. Parameters relating to cell morphology, viability, proliferation, and migration were analysed using breast cancer MCF-7 cells. In a xenograft model, secretion of angiogenesis-related growth factors and the anti-angiogenic efficacy of Endostar and Bevacizumab in cells grown in HECS-GMA hydrogels were assessed by immunohistochemistry. Hydroxyethyl chitosan/glycidyl methacrylate hydrogels had a highly porous microstructure, mechanical properties, swelling ratio, and morphology consistent with a 3D tumour model. Compared with a 2D monolayer culture, breast cancer MCF-7 cells residing in the HECS-GMA hydrogels grew as tumour-like clusters in a 3D formation. In a xenograft model, MCF-7 cells cultured in the HECS-GMA hydrogels had increased secretion of angiogenesis-related growth factors. Recombinant human endostatin (Endostar), but not Bevacizumab (Avastin), was an effective anti-angiogenic agent in HECS-GMA hydrogels. The HECS-GMA hydrogel provided a 3D tumour model that mimicked the in vivo cancer microenvironment and supported the growth of MCF7 cells better than traditional tissue culture plates. The HECS-GMA hydrogel may offer an improved platform to minimize the gap between traditional tissue culture plates and clinical applicability. In addition, the anti-angiogenic efficacy of drugs such as Endostar and Bevacizumab can be more comprehensively studied and assessed in HECS-GMA hydrogels.

Cost-utility and budget impact analyses of the use of NEPA for chemotherapy-induced nausea and vomiting prophylaxis in Italy

PubMed Central

Restelli, Umberto; Saibene, Gabriella; Nardulli, Patrizia; Di Turi, Roberta; Bonizzoni, Erminio; Scolari, Francesca; Perrone, Tania; Croce, Davide; Celio, Luigi

2017-01-01

Objective To evaluate the efficiency of resources allocation and sustainability of the use of netupitant+palonosetron (NEPA) for chemotherapy-induced nausea and vomiting (CINV) prophylaxis assuming the Italian National Health Service (NHS) perspective. A published Markov model was adapted to assess the incremental cost-utility ratio of NEPA compared with aprepitant (APR) + palonosetron (PALO), fosaprepitant (fAPR) + PALO, APR + ondansetron (ONDA), fAPR + ONDA in patients receiving a highly emetogenic chemotherapy (HEC) and with APR + PALO and fAPR + PALO in patients receiving a moderately emetogenic chemotherapy (MEC). Setting Oncology hospital department in Italy. Methods A Markov model was used to determine the impact of NEPA on the budget of the Italian NHS on a 5-day time horizon, corresponding to the acute and delayed CINV prophylaxis phases. Direct medical costs considered were related to antiemetic drugs, adverse events management, CINV episodes management. Clinical and quality of life data referred to previously published works. The budget impact analysis considered the aforementioned therapies plus PALO alone (for HEC and MEC) on a 5-year time horizon, comparing two scenarios: one considering the use of NEPA and one not considering its use. Primary and secondary outcome measures Incremental cost per quality adjusted life year (QALY) and differential economic impact for the Italian NHS between the two scenarios considered. Results NEPA is more effective and less expensive (dominant) compared with APR + PALO (for HEC and MEC), fAPR + PALO (for HEC and MEC), APR + ONDA (for HEC), fAPR + ONDA (for HEC). The use of NEPA would lead to a 5-year cost decrease of €63.7 million (€42.7 million for HEC and €20.9 million for MEC). Conclusions NEPA allows an efficient allocation of resources for the Italian NHS and it is sustainable, leading to a cost decrease compared with a scenario which does not consider its use. PMID:28765126

Effects of mutant human Ki-ras{sup G12C} gene dosage on murine lung tumorigenesis and signaling to its downstream effectors

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

Dance-Barnes, Stephanie T.; Kock, Nancy D.; Floyd, Heather S.

2008-08-15

Studies in cell culture have suggested that the level of RAS expression can influence the transformation of cells and the signaling pathways stimulated by mutant RAS expression. However, the levels of RAS expression in vivo appear to be subject to feedback regulation, limiting the total amount of RAS protein that can be expressed. We utilized a bitransgenic mouse lung tumor model that expressed the human Ki-ras{sup G12C} allele in a tetracycline-inducible, lung-specific manner. Treatment for 12 months with 500 {mu}g/ml of doxycycline (DOX) allowed for maximal expression of the human Ki-ras{sup G12C} allele in the lung, and resulted in themore » development of focal hyperplasia and adenomas. We determined if different levels of mutant RAS expression would influence the phenotype of the lung lesions. Treatment with 25, 100 and 500 {mu}g/ml of DOX resulted in dose-dependent increases in transgene expression and tumor multiplicity. Microscopic analysis of the lungs of mice treated with the 25 {mu}g/ml dose of DOX revealed infrequent foci of hyperplasia, whereas mice treated with the 100 and 500 {mu}g/ml doses exhibited numerous hyperplastic foci and also adenomas. Immunohistochemical and RNA analysis of the downstream effector pathways demonstrated that different levels of mutant RAS transgene expression resulted in differences in the expression and/or phosphorylation of specific signaling molecules. Our results suggest that the molecular alterations driving tumorigenesis may differ at different levels of mutant Ki-ras{sup G12C} expression, and this should be taken into consideration when inducible transgene systems are utilized to promote tumorigenesis in mouse models.« less

Review: Intracardiac intracellular angiotensin system in diabetes

PubMed Central

Kumar, Rajesh; Yong, Qian Chen; Thomas, Candice M.

2012-01-01

The renin-angiotensin system (RAS) has mainly been categorized as a circulating and a local tissue RAS. A new component of the local system, known as the intracellular RAS, has recently been described. The intracellular RAS is defined as synthesis and action of ANG II intracellularly. This RAS appears to differ from the circulating and the local RAS, in terms of components and the mechanism of action. These differences may alter treatment strategies that target the RAS in several pathological conditions. Recent work from our laboratory has demonstrated significant upregulation of the cardiac, intracellular RAS in diabetes, which is associated with cardiac dysfunction. Here, we have reviewed evidence supporting an intracellular RAS in different cell types, ANG II's actions in cardiac cells, and its mechanism of action, focusing on the intracellular cardiac RAS in diabetes. We have discussed the significance of an intracellular RAS in cardiac pathophysiology and implications for potential therapies. PMID:22170614

Numerical modeling techniques for flood analysis

NASA Astrophysics Data System (ADS)

Anees, Mohd Talha; Abdullah, K.; Nawawi, M. N. M.; Ab Rahman, Nik Norulaini Nik; Piah, Abd. Rahni Mt.; Zakaria, Nor Azazi; Syakir, M. I.; Mohd. Omar, A. K.

2016-12-01

Topographic and climatic changes are the main causes of abrupt flooding in tropical areas. It is the need to find out exact causes and effects of these changes. Numerical modeling techniques plays a vital role for such studies due to their use of hydrological parameters which are strongly linked with topographic changes. In this review, some of the widely used models utilizing hydrological and river modeling parameters and their estimation in data sparse region are discussed. Shortcomings of 1D and 2D numerical models and the possible improvements over these models through 3D modeling are also discussed. It is found that the HEC-RAS and FLO 2D model are best in terms of economical and accurate flood analysis for river and floodplain modeling respectively. Limitations of FLO 2D in floodplain modeling mainly such as floodplain elevation differences and its vertical roughness in grids were found which can be improve through 3D model. Therefore, 3D model was found to be more suitable than 1D and 2D models in terms of vertical accuracy in grid cells. It was also found that 3D models for open channel flows already developed recently but not for floodplain. Hence, it was suggested that a 3D model for floodplain should be developed by considering all hydrological and high resolution topographic parameter's models, discussed in this review, to enhance the findings of causes and effects of flooding.

Validation of Methods to Control for Immortal Time Bias in a Pharmacoepidemiologic Analysis of Renin–Angiotensin System Inhibitors in Type 2 Diabetes

PubMed Central

Yang, Xilin; Kong, Alice PS; Luk, Andrea OY; Ozaki, Risa; Ko, Gary TC; Ma, Ronald CW; Chan, Juliana CN; So, Wing Yee

2014-01-01

Background Pharmacoepidemiologic analysis can confirm whether drug efficacy in a randomized controlled trial (RCT) translates to effectiveness in real settings. We examined methods used to control for immortal time bias in an analysis of renin–angiotensin system (RAS) inhibitors as the reference cardioprotective drug. Methods We analyzed data from 3928 patients with type 2 diabetes who were recruited into the Hong Kong Diabetes Registry between 1996 and 2005 and followed up to July 30, 2005. Different Cox models were used to obtain hazard ratios (HRs) for cardiovascular disease (CVD) associated with RAS inhibitors. These HRs were then compared to the HR of 0.92 reported in a recent meta-analysis of RCTs. Results During a median follow-up period of 5.45 years, 7.23% (n = 284) patients developed CVD and 38.7% (n = 1519) were started on RAS inhibitors, with 39.1% of immortal time among the users. In multivariable analysis, time-dependent drug-exposure Cox models and Cox models that moved immortal time from users to nonusers both severely inflated the HR, and time-fixed models that included immortal time deflated the HR. Use of time-fixed Cox models that excluded immortal time resulted in a HR of only 0.89 (95% CI, 0.68–1.17) for CVD associated with RAS inhibitors, which is closer to the values reported in RCTs. Conclusions In pharmacoepidemiologic analysis, time-dependent drug exposure models and models that move immortal time from users to nonusers may introduce substantial bias in investigations of the effects of RAS inhibitors on CVD in type 2 diabetes. PMID:24747198

Design and synthesis of a novel cationic thiolated polymer.

PubMed

Rahmat, Deni; Sakloetsakun, Duangkamon; Shahnaz, Gul; Perera, Glen; Kaindl, Reinhard; Bernkop-Schnürch, Andreas

2011-06-15

The purpose of this study was to design and characterize a novel cationic thiolated polymer. In this regard a hydroxyethylcellulose-cysteamine conjugate (HEC-cysteamine) was synthesized. Oxidative ring opening with periodate and reductive amination with cysteamine were performed in order to immobilize free thiol groups to HEC. The resulting HEC-cysteamine displayed 2035 ± 162 μmol immobilized free thiol groups and 185 ± 64 μmol disulfide bonds per gram of polymer being soluble in both acidic and basic conditions. Unlike the unmodified HEC, in case of HEC-cysteamine, a three-fold increase in the viscosity was observed when equal volumes of the polymer were mixed with mucin solution. Tablets based on HEC-cysteamine remained attached on freshly excised porcine mucosa for 8 0h and displayed increased disintegration time of 2h. Swelling behavior of HEC-cysteamine tablets in 0.1M phosphate buffer pH 6.8 indicated swelling ratio of 19 within 8h. In contrast, tablets comprising unmodified HEC detached from the mucosa within few seconds and immediately disintegrated. In addition, they did not exhibit swelling behavior. The transport of rhodamine 123 across freshly excised rat intestine enhanced by a value of approximately 1.6-fold (p-value = 0.0024) in the presence of 0.5% (m/v) HEC-cysteamine as compared to buffer control. Result from cytotoxicity test of HEC-cysteamine applied to Caco-2 cells in concentration of 0.5% (m/v) revealed 82.4 ± 4.60% cell viability. According to these results, HEC-cysteamine seems to be a promising polymer for various pharmaceutical applications especially for intestinal drug delivery. Copyright © 2011. Published by Elsevier B.V.

Clinical Practices and Outcomes on Chemotherapy-Induced Nausea and Vomiting Management in South Korea: Comparison with Asia-Pacific Data of the Pan Australasian Chemotherapy Induced Emesis Burden of Illness Study

PubMed Central

Lee, Myung Ah; Cho, Eun Kyung; Oh, Sung Yong; Ahn, Joong Bae; Lee, Ji Yun; Thomas, Burke; Jung, Hun; Kim, Jong Gwang

2016-01-01

Purpose This study reported patient outcomes of chemotherapy-induced nausea and vomiting (CINV) prophylaxis for highly emetogenic chemotherapy (HEC) and moderately emetogenic chemotherapy (MEC) regimens and evaluated its adherence to acute-phase CINV prophylaxis in the Korean population subset of the Pan Australasian Chemotherapy Induced Emesis burden of illness (PrACTICE) study. Materials and Methods This subgroup analysis evaluated 158 Korean patients receiving HEC or MEC and compared the data (wherever possible) with that of 648 patients from the Asia-Pacific (AP) region. Study endpoints included evaluation of primary CINV prophylaxis and adherence to acute-phase CINV prophylaxis in cycle 1 (American Society of Clinical Oncology [ASCO] Quality Oncology Practice Initiative [QOPI]). Results In South Korea and the AP, a 5-hydroxytryptamine-3 receptor antagonist (5HT3-RA) prophylaxis for the acute phase was administered to 79/80 patients (98.8%) for HEC and 70/71 patients (98.6%) for MEC regimens (QOPI-1). Triple regimen (corticosteroid–5HT3-RA–neurokinin 1-RA) was initiated in 46/80 patients (57.5%) for prophylaxis of acute CINV in cycle 1 of HEC (QOPI-3). Double regimen (corticosteroid–5HT3-RA, with or within NK1-RA) was initiated in 61/71 patients (83.1%) for control of acute CINV in cycle 1 of MEC a(QOPI-2). Conclusion Active management of CINV is necessary in cycle 1 of HEC in South Korea, despite higher rates than the AP region. Adherence to the international guidelines for CINV prophylaxis requires attention in the acute phase in cycle 1 of the HEC regimen. PMID:26875197

Sediment Transport Dynamic in a Meandering Fluvial System: Case Study of Chini River

NASA Astrophysics Data System (ADS)

Nazir, M. H. M.; Awang, S.; Shaaban, A. J.; Yahaya, N. K. E. M.; Jusoh, A. M.; Arumugam, M. A. R. M. A.; Ghani, A. A.

2016-07-01

Sedimentation in river reduces the flood carrying capacity which lead to the increasing of inundation area in the river basin. Basic sediment transport can predict the fluvial processes in natural rivers and stream through modeling approaches. However, the sediment transport dynamic in a small meandering and low-lying fluvial system is considered scarce in Malaysia. The aim of this study was to analyze the current riverbed erosion and sedimentation scenarios along the Chini River, Pekan, Pahang. The present study revealed that silt and clay has potentially been eroded several parts of the river. Sinuosity index (1.98) indicates that Chini River is very unstable and continuous erosion process in waterways has increase the riverbank instability due to the meandering factors. The riverbed erosional and depositional process in the Chini River is a sluggish process since the lake reduces the flow velocity and causes the deposited particles into the silt and clay soil at the bed of the lake. Besides, the bed layer of the lake comprised of cohesive silt and clayey composition that tend to attach the larger grain size of sediment. The present study estimated the total sediment accumulated along the Chini River is 1.72 ton. The HEC-RAS was employed in the simulations and in general the model performed well, once all parameters were set within their effective ranges.

Ha-ras(val12) induces HSP70b transcription via the HSE/HSF1 system, but HSP70b expression is suppressed in Ha-ras(val12)-transformed cells.

PubMed

Stanhill, A; Levin, V; Hendel, A; Shachar, I; Kazanov, D; Arber, N; Kaminski, N; Engelberg, D

2006-03-09

Heat shock proteins (Hsps) are overexpressed in many tumors, but are downregulated in some tumors. To check for a direct effect of Ha-Ras(val12) on HSP70 transcription, we transiently expressed the oncoprotein in Rat1 fibroblasts and monitored its effect on HSP70b promoter-driven reporter gene. We show that expression of Ha-Ras(val12) induced this promoter. Promoter analysis via systematic deletions and point mutations revealed that Ha-Ras(val12) induces HSP70b transcription via heat shock elements (HSEs). Also, Ha-Ras(val12) induction of HSE-mediated transcription was dramatically reduced in HSF1-/- cells. Yet, residual effect of Ha-Ras(val12) that was still measured in HSF1-/- cells suggests that some of the Ha-Ras(val12) effect is Hsf1-independent. When HSF1-/- cells, stably expressing Ha-Ras(val12), were grown on soft agar only small colonies were formed suggesting a role for heat shock factor 1 (Hsf1) in Ha-Ras(val12)-mediated transformation. Although Ha-ras(Val12) seems to be an inducer of HSP70's expression, we found that in Ha-ras(Val12-)transformed fibroblasts expression of this gene is suppressed. This suppression is correlated with higher sensitivity of Ha-ras(val12)-transformed cells to heat shock. We suggest that Ha-ras(Val12) is involved in Hsf1 activation, thereby inducing the cellular protective response. Cells that repress this response are perhaps those that acquire the capability to further proliferate and become transformed clones.

Stimuli sensitive super-macroporous cryogels based on photo-crosslinked 2-hydroxyethylcellulose and chitosan.

PubMed

Stoyneva, Veselina; Momekova, Denitsa; Kostova, Bistra; Petrov, Petar

2014-01-01

Original pH sensitive cryogels, based on two biodegradable natural polymers chitosan (CS) and 2-hydroxyethylcellulose (HEC), were obtained via cryogenic treatment of semi-dilute aqueous solutions and UV induced crosslinking in frozen state. H₂O₂ and N,N'-methylenebisacrylamide (BisAAm) were used as photoinitiator and crosslinking agent, respectively. BisAAm facilitated the formation of polymer co-network and increased both the gel fraction yield and mechanical strength of cryogels. The influence of chitosan content on the physico-mechanical properties of HEC-CS cryogels was investigated. In general, the increase of CS fraction in the polymer co-network increased the degree of swelling and enhanced significantly the storage modulus of materials. All HEC-CS cryogels obtained were opalescent sponge-like materials, which quickly release/uptake water due to their open porous structure. The incorporation of CS provided pH dependent swelling and good bioadhesive properties of cryogels. HEC-CS cryogels were further exploited as drug delivery systems of the highly water soluble drug metronidazole belonging to BCS Class l. Copyright © 2013 Elsevier Ltd. All rights reserved.

Phosphorylation of microtubule-binding protein Hec1 by mitotic kinase Aurora B specifies spindle checkpoint kinase Mps1 signaling at the kinetochore.

PubMed

Zhu, Tongge; Dou, Zhen; Qin, Bo; Jin, Changjiang; Wang, Xinghui; Xu, Leilei; Wang, Zhaoyang; Zhu, Lijuan; Liu, Fusheng; Gao, Xinjiao; Ke, Yuwen; Wang, Zhiyong; Aikhionbare, Felix; Fu, Chuanhai; Ding, Xia; Yao, Xuebiao

2013-12-13

The spindle assembly checkpoint (SAC) is a quality control device to ensure accurate chromosome attachment to spindle microtubule for equal segregation of sister chromatid. Aurora B is essential for SAC function by sensing chromosome bi-orientation via spatial regulation of kinetochore substrates. However, it has remained elusive as to how Aurora B couples kinetochore-microtubule attachment to SAC signaling. Here, we show that Hec1 interacts with Mps1 and specifies its kinetochore localization via its calponin homology (CH) domain and N-terminal 80 amino acids. Interestingly, phosphorylation of the Hec1 by Aurora B weakens its interaction with microtubules but promotes Hec1 binding to Mps1. Significantly, the temporal regulation of Hec1 phosphorylation orchestrates kinetochore-microtubule attachment and Mps1 loading to the kinetochore. Persistent expression of phosphomimetic Hec1 mutant induces a hyperactivation of SAC, suggesting that phosphorylation-elicited Hec1 conformational change is used as a switch to orchestrate SAC activation to concurrent destabilization of aberrant kinetochore attachment. Taken together, these results define a novel role for Aurora B-Hec1-Mps1 signaling axis in governing accurate chromosome segregation in mitosis.

Phosphorylation of Microtubule-binding Protein Hec1 by Mitotic Kinase Aurora B Specifies Spindle Checkpoint Kinase Mps1 Signaling at the Kinetochore*

PubMed Central

Zhu, Tongge; Dou, Zhen; Qin, Bo; Jin, Changjiang; Wang, Xinghui; Xu, Leilei; Wang, Zhaoyang; Zhu, Lijuan; Liu, Fusheng; Gao, Xinjiao; Ke, Yuwen; Wang, Zhiyong; Aikhionbare, Felix; Fu, Chuanhai; Ding, Xia; Yao, Xuebiao

2013-01-01

The spindle assembly checkpoint (SAC) is a quality control device to ensure accurate chromosome attachment to spindle microtubule for equal segregation of sister chromatid. Aurora B is essential for SAC function by sensing chromosome bi-orientation via spatial regulation of kinetochore substrates. However, it has remained elusive as to how Aurora B couples kinetochore-microtubule attachment to SAC signaling. Here, we show that Hec1 interacts with Mps1 and specifies its kinetochore localization via its calponin homology (CH) domain and N-terminal 80 amino acids. Interestingly, phosphorylation of the Hec1 by Aurora B weakens its interaction with microtubules but promotes Hec1 binding to Mps1. Significantly, the temporal regulation of Hec1 phosphorylation orchestrates kinetochore-microtubule attachment and Mps1 loading to the kinetochore. Persistent expression of phosphomimetic Hec1 mutant induces a hyperactivation of SAC, suggesting that phosphorylation-elicited Hec1 conformational change is used as a switch to orchestrate SAC activation to concurrent destabilization of aberrant kinetochore attachment. Taken together, these results define a novel role for Aurora B-Hec1-Mps1 signaling axis in governing accurate chromosome segregation in mitosis. PMID:24187132

Impact of periodic health examination on surgical treatment for uterine fibroids in Beijing: a case-control study.

PubMed

Wu, Hai-Yun; Yang, Ling-Ling; Zhou, Shan

2010-12-07

During the past 2 decades, there has been a rapid proliferation of "health examination center (HEC)" across China. The effects of their services on public's health have not been systemically investigated. This study aimed to assess the impact of periodic health examination (PHE) at HEC on surgical treatment for uterine fibroids in Beijing residents. We identified 224 patients with a primary diagnosis of uterine fibroids who had surgical treatment at four Level-1 general hospitals in Beijing, from June 1, 2009 to October 20, 2009. Controls were women who did not have surgery for uterine fibroids, matched (1:1 ratio) for age (within 2 years). A standard questionnaire was used to inquire about whether participants had PHE at HEC during the previous 2 years. PHE at HEC within 2 years were associated with surgical treatment for uterine fibroids. Odds ratios was 4.05 (95% CI, 2.61-6.29 P < 0.001), after adjustment for marital status, whether have children, annual family income, health insurance, education level and self-rated uterine fibroids-related symptom severity. Our study showed PHE currently provided at HEC in China were associated with significantly increased use of surgical treatment for uterine fibroids in women. Further studies are needed to assess the effects of PHE on clinical as well as on broad societal outcomes in Chinese in contemporary medical settings.

Geomorphological and sedimentological analysis of flash-flood deposits: The case of the 1997 Rivillas flood (Spain)

NASA Astrophysics Data System (ADS)

Ortega, Jose A.; Garzón Heydt, Guillermina

2009-11-01

On the basis of the description of the 1997 Rivillas flood deposits, a morphosedimentary feature classification is proposed. Mapping of the main morphosedimentary deposits in seven reaches along the basin has provided abundant data for each defined typology and for a better adjustment of their stability fields. Because of their unstable preservation environment, immediate post-flood field surveys with descriptions of erosive and depositional features were undertaken. Up to 18 features were classified as either sedimentary or erosive and mapped according to their genetic environments. Anthropic interference such as land use changes produce modification of sediment supply and in channel and floodplain erosive processes causing flash-floods to be more catastrophic. Erosive features are dominant over sedimentary ones, as the sedimentary budget in the river is negative. By means of HEC-RAS (Hydrologic Engineering Center) modelling, we were able to obtain mean values of the main variables limiting feature stability (velocity, depth, stream powers and shear stress). These provide information regarding maximum stability threshold and peak flood discharge. The ephemeral nature of riverine flash-flood deposits in this type of setting does not mean that they are not significant, and their interpretation after recent floods can significantly improve interpretation of the event dynamics and its flood hydrology and also be useful for flood risk mapping.

A regulatory framework for shoot stem cell control integrating metabolic, transcriptional, and phytohormone signals.

PubMed

Schuster, Christoph; Gaillochet, Christophe; Medzihradszky, Anna; Busch, Wolfgang; Daum, Gabor; Krebs, Melanie; Kehle, Andreas; Lohmann, Jan U

2014-02-24

Plants continuously maintain pluripotent stem cells embedded in specialized tissues called meristems, which drive long-term growth and organogenesis. Stem cell fate in the shoot apical meristem (SAM) is controlled by the homeodomain transcription factor WUSCHEL (WUS) expressed in the niche adjacent to the stem cells. Here, we demonstrate that the bHLH transcription factor HECATE1 (HEC1) is a target of WUS and that it contributes to SAM function by promoting stem cell proliferation, while antagonizing niche cell activity. HEC1 represses the stem cell regulators WUS and CLAVATA3 (CLV3) and, like WUS, controls genes with functions in metabolism and hormone signaling. Among the targets shared by HEC1 and WUS are phytohormone response regulators, which we show to act as mobile signals in a universal feedback system. Thus, our work sheds light on the mechanisms guiding meristem function and suggests that the underlying regulatory system is far more complex than previously anticipated. Copyright © 2014 Elsevier Inc. All rights reserved.

The renin-angiotensin system in thyroid disorders and its role in cardiovascular and renal manifestations.

PubMed

Vargas, Félix; Rodríguez-Gómez, Isabel; Vargas-Tendero, Pablo; Jimenez, Eugenio; Montiel, Mercedes

2012-04-01

Thyroid disorders are among the most common endocrine diseases and affect virtually all physiological systems, with an especially marked impact on cardiovascular and renal systems. This review summarizes the effects of thyroid hormones on the renin-angiotensin system (RAS) and the participation of the RAS in the cardiovascular and renal manifestations of thyroid disorders. Thyroid hormones are important regulators of cardiac and renal mass, vascular function, renal sodium handling, and consequently blood pressure (BP). The RAS acts globally to control cardiovascular and renal functions, while RAS components act systemically and locally in individual organs. Various authors have implicated the systemic and local RAS in the mediation of functional and structural changes in cardiovascular and renal tissues due to abnormal thyroid hormone levels. This review analyzes the influence of thyroid hormones on RAS components and discusses the role of the RAS in BP, cardiac mass, vascular function, and renal abnormalities in thyroid disorders.

Changes in the renin angiotensin system during the development of colorectal cancer liver metastases.

PubMed

Neo, Jaclyn H; Ager, Eleanor I; Angus, Peter W; Zhu, Jin; Herath, Chandana B; Christophi, Christopher

2010-04-10

Blockade of the renin angiotensin system (RAS) via angiotensin I converting enzyme (ACE) inhibition reduces growth of colorectal cancer (CRC) liver metastases in a mouse model. In this work we defined the expression of the various components of the RAS in both tumor and liver during the progression of this disease. Immunohistochemistry and quantitative RT-PCR was used to examine RAS expression in a mouse CRC liver metastases model. CRC metastases and liver tissue was assessed separately at key stages of CRC liver metastases development in untreated (control) mice and in mice treated with the ACE inhibitor captopril (750 mg/kg/day). Non-tumor induced (sham) mice indicated the effect of tumors on normal liver RAS. The statistical significance of multiple comparisons was determined using one-way analysis of variance followed by Bonferroni adjustment with SAS/STAT software. Reduced volume of CRC liver metastases with captopril treatment was evident. Local RAS of CRC metastases differed from the surrounding liver, with lower angiotensin II type 1 receptor (AT1R) expression but increased ANG-(1-7) receptor (MasR) compared to the liver. The AT1R localised to cancer and stromal infiltrating cells, while other RAS receptors were detected in cancer cells only. Tumor induction led to an initial increase in AT1R and ACE expression while captopril treatment significantly increased ACE expression in the final stages of tumor growth. Conversely, captopril treatment decreased expression of AT1R and angiotensinogen. These results demonstrate significant changes in RAS expression in the tumor-bearing captopril treated liver and in CRC metastases. The data suggests the existence of a tumor-specific RAS that can be independently targeted by RAS blockade.

Changes in the renin angiotensin system during the development of colorectal cancer liver metastases

PubMed Central

2010-01-01

Background Blockade of the renin angiotensin system (RAS) via angiotensin I converting enzyme (ACE) inhibition reduces growth of colorectal cancer (CRC) liver metastases in a mouse model. In this work we defined the expression of the various components of the RAS in both tumor and liver during the progression of this disease. Methods Immunohistochemistry and quantitative RT-PCR was used to examine RAS expression in a mouse CRC liver metastases model. CRC metastases and liver tissue was assessed separately at key stages of CRC liver metastases development in untreated (control) mice and in mice treated with the ACE inhibitor captopril (750 mg/kg/day). Non-tumor induced (sham) mice indicated the effect of tumors on normal liver RAS. The statistical significance of multiple comparisons was determined using one-way analysis of variance followed by Bonferroni adjustment with SAS/STAT software. Results Reduced volume of CRC liver metastases with captopril treatment was evident. Local RAS of CRC metastases differed from the surrounding liver, with lower angiotensin II type 1 receptor (AT1R) expression but increased ANG-(1-7) receptor (MasR) compared to the liver. The AT1R localised to cancer and stromal infiltrating cells, while other RAS receptors were detected in cancer cells only. Tumor induction led to an initial increase in AT1R and ACE expression while captopril treatment significantly increased ACE expression in the final stages of tumor growth. Conversely, captopril treatment decreased expression of AT1R and angiotensinogen. Conclusions These results demonstrate significant changes in RAS expression in the tumor-bearing captopril treated liver and in CRC metastases. The data suggests the existence of a tumor-specific RAS that can be independently targeted by RAS blockade. PMID:20380732

Changing stakeholder relationships in nature reserve management: a case study on Snake Island-Laotie Mountain National Nature Reserve, Liaoning, China.

PubMed

Zhou, Dan; Wang, Ziyan; Lassoie, James; Wang, Xiaoping; Sun, Lixin

2014-12-15

The number and total area of nature reserves in China has increased rapidly over the past couple of decades; however, the ability to effectively manage these reserves has not kept pace and conflicts between conservation efforts and economic development have emerged. The Snake Island-Laotie Mountain National Nature Reserve (SILMNNR) currently is experiencing the challenges of balancing conservation with local community development. This paper uses components analysis of human ecosystems (HEC) to examine conflicts arising from the management of the nature reserve and uses a stakeholder analysis to identify and better understand stakeholder inter-relationships in the SILMNNR-HEC. The goal of this study is to identify critical factors influencing stakeholder relationships in order to find ways of relieving conflicts between the reserve management and development. The stakeholder analysis revealed that the key stakeholders in the SILMNNR-HEC are natural resources, the Liaoning SILMNNR Authority, local residents, and enterprise developers; however, there was unequal power among stakeholders in the decision making process affecting the nature reserve. The paper evaluated the conditions and processes of SILMNNR-HEC through a framework of stakeholder relationships where critical factors, such as policy, finance, technology, and labor, and their respective strengths and feedbacks among stakeholders, were assessed and showed unequal flows of power among stakeholders. Two approaches are provided for transforming the unbalanced relationships into a stable and sustainable framework to sustainably manage the nature reserve: the first is by changing stakeholder relationships from opposition to cooperation; and the second by enhancing feedbacks and dynamics among stakeholders. The analysis used in this paper can be used as a model to assess conflicts around other protected areas in China and elsewhere. Copyright © 2014 Elsevier Ltd. All rights reserved.

Renal artery stenosis in children: therapeutic percutaneous balloon and stent angioplasty.

PubMed

Colyer, Jessica H; Ratnayaka, Kanishka; Slack, Michael C; Kanter, Joshua P

2014-06-01

Renal artery stenosis (RAS) accounts for 10 % of cases of systemic hypertension in children. Initial management involves anti-hypertensive therapy. Percutaneous interventions are documented for the treatment of RAS in the adult population. In children, case reports suggest benefit. This is a retrospective analysis of consecutive patients referred for catheterization for RAS between 2002 and 2010 at a single institution. Recorded variables included: age, weight, systemic blood pressure, minimal luminal diameter, interventional devices, antihypertensive medications, contrast volume, and complications. Twelve patients (median age 8.2, IQR 6-12.4 years); median weight 42.8 kg, IQR: 25-47.4 kg) were referred for renal artery catheterization and underwent percutaneous intervention. Overall, minimal luminal diameter (MLD) increased by 1.2 ± 0.9 mm for all patients (p < 0.05) and by 1.3 ± 0.9 mm for post-renal transplant patients (p < 0.05). Only stent angioplasty patients demonstrated significant improved blood pressure (p < 0.05). One patient had stent thrombosis requiring re-intervention with repeat balloon angioplasty. This retrospective analysis suggests that percutaneous intervention might play a role in the management of RAS, with an improvement in MLD in children with RAS. Transcatheter intervention is technically feasible with low morbidity. A prospective, longitudinal study is warranted to compare standard medical therapy with percutaneous interventions.

Land cover change impact on urban flood modeling (case study: Upper Citarum watershed)

NASA Astrophysics Data System (ADS)

Siregar, R. I.

2018-03-01

The upper Citarum River watershed utilizes remote sensing technology in Geographic Information System to provide information on land coverage by interpretation of objects in the image. Rivers that pass through urban areas will cause flooding problems causing disadvantages, and it disrupts community activities in the urban area. Increased development in a city is related to an increase in the number of population growth that added by increasing quality and quantity of life necessities. Improved urban lifestyle changes have an impact on land cover. The impact in over time will be difficult to control. This study aims to analyze the condition of flooding in urban areas caused by upper Citarum watershed land-use change in 2001 with the land cover change in 2010. This modeling analyzes with the help of HEC-RAS to describe flooded inundation urban areas. Land cover change in upper Citarum watershed is not very significant; it based on the results of data processing of land cover has the difference of area that changed is not enormous. Land cover changes for the floods increased dramatically to a flow coefficient for 2001 is 0.65 and in 2010 at 0.69. In 2001, the inundation area about 105,468 hectares and it were about 92,289 hectares in 2010.

A probabilistic bridge safety evaluation against floods.

PubMed

Liao, Kuo-Wei; Muto, Yasunori; Chen, Wei-Lun; Wu, Bang-Ho

2016-01-01

To further capture the influences of uncertain factors on river bridge safety evaluation, a probabilistic approach is adopted. Because this is a systematic and nonlinear problem, MPP-based reliability analyses are not suitable. A sampling approach such as a Monte Carlo simulation (MCS) or importance sampling is often adopted. To enhance the efficiency of the sampling approach, this study utilizes Bayesian least squares support vector machines to construct a response surface followed by an MCS, providing a more precise safety index. Although there are several factors impacting the flood-resistant reliability of a bridge, previous experiences and studies show that the reliability of the bridge itself plays a key role. Thus, the goal of this study is to analyze the system reliability of a selected bridge that includes five limit states. The random variables considered here include the water surface elevation, water velocity, local scour depth, soil property and wind load. Because the first three variables are deeply affected by river hydraulics, a probabilistic HEC-RAS-based simulation is performed to capture the uncertainties in those random variables. The accuracy and variation of our solutions are confirmed by a direct MCS to ensure the applicability of the proposed approach. The results of a numerical example indicate that the proposed approach can efficiently provide an accurate bridge safety evaluation and maintain satisfactory variation.

Extreme Changes in Stream Geomorphic Conditions induced by Fluvial Scour in Bridges

NASA Astrophysics Data System (ADS)

Özcan, O.; Ozcan, O.

2016-12-01

The numerous complexities associated with bridge scour have caused scour to be one of the most active topics of stream geomorphic research. The assessment of local scouring mechanism around bridge piers provides information for decision-making regarding the pile footing design, predicting the safety of bridges under critical scoured conditions, and as a result, may help prevent unnecessary loses. In the study, bridge design plans and HEC-RAS modeling were used for the assessment of changes in stream geomorphic conditions. The derived fluvial scour depths were compared with the field measurements and the empirical formula which is based on stream flow discharge rate, streambed condition and shape of river. Preliminary results revealed that bridge damage resulting from the flood event in 2003 induced substantial scour around bridge piles. Afterwards, significant stream bed change was observed under the influence of fluvial scour in another flood occurred in 2009. Consequently, geomorphic conditions of the stream bed should be considered in the structural design of the bridges.

An inverse method to estimate the flow through a levee breach

NASA Astrophysics Data System (ADS)

D'Oria, Marco; Mignosa, Paolo; Tanda, Maria Giovanna

2015-08-01

We propose a procedure to estimate the flow through a levee breach based on water levels recorded in river stations downstream and/or upstream of the failure site. The inverse problem is solved using a Bayesian approach and requires the execution of several forward unsteady flow simulations. For this purpose, we have used the well-known 1-D HEC-RAS model, but any unsteady flow model could be adopted in the same way. The procedure has been tested using four synthetic examples. Levee breaches with different characteristics (free flow, flow with tailwater effects, etc.) have been simulated to collect the synthetic level data used at a later stage in the inverse procedure. The method was able to accurately reproduce the flow through the breach in all cases. The practicability of the procedure was then confirmed applying it to the inundation of the Polesine Region (Northern Italy) which occurred in 1951 and was caused by three contiguous and almost simultaneous breaches on the left embankment of the Po River.

Metabolic Rate Regulation by the Renin-Angiotensin System: Brain vs. Body

PubMed Central

Grobe, Justin L.; Rahmouni, Kamal; Liu, Xuebo; Sigmund, Curt D.

2013-01-01

Substantial evidence supports a role for the renin-angiotensin system (RAS) in the regulation of metabolic function, but an apparent paradox exists where genetic or pharmacological inhibition of the RAS occasionally have similar physiological effects as chronic angiotensin infusion. Similarly, while RAS targeting in animal models has robust metabolic consequences, effects in humans are more subtle. Here we review the data supporting a role for the RAS in metabolic rate regulation and propose a model where the local brain RAS works in opposition to the peripheral RAS, thus helping to explain the paradoxically similar effects of RAS supplementation and inhibition. Selectively modulating the peripheral RAS or brain RAS may thus provide a more effective treatment paradigm for obesity and obesity-related disorders. PMID:22491893

Qualitative simulation of bathymetric changes due to reservoir sedimentation: A Japanese case study

PubMed Central

Dai, Wenhong; Larson, Magnus; Beebo, Qaid Naamo; Xie, Qiancheng

2017-01-01

Sediment-dynamics modeling is a useful tool for estimating a dam’s lifespan and its cost–benefit analysis. Collecting real data for sediment-dynamics analysis from conventional field survey methods is both tedious and expensive. Therefore, for most rivers, the historical record of data is either missing or not very detailed. Available data and existing tools have much potential and may be used for qualitative prediction of future bathymetric change trend. This study shows that proxy approaches may be used to increase the spatiotemporal resolution of flow data, and hypothesize the river cross-sections and sediment data. Sediment-dynamics analysis of the reach of the Tenryu River upstream of Sakuma Dam in Japan was performed to predict its future bathymetric changes using a 1D numerical model (HEC-RAS). In this case study, only annually-averaged flow data and the river’s longitudinal bed profile at 5-year intervals were available. Therefore, the other required data, including river cross-section and geometry and sediment inflow grain sizes, had to be hypothesized or assimilated indirectly. The model yielded a good qualitative agreement, with an R2 (coefficient of determination) of 0.8 for the observed and simulated bed profiles. A predictive simulation demonstrated that the useful life of the dam would end after the year 2035 (±5 years), which is in conformity with initial detailed estimates. The study indicates that a sediment-dynamic analysis can be performed even with a limited amount of data. However, such studies may only assess the qualitative trends of sediment dynamics. PMID:28384361

Qualitative simulation of bathymetric changes due to reservoir sedimentation: A Japanese case study.

PubMed

Bilal, Ahmed; Dai, Wenhong; Larson, Magnus; Beebo, Qaid Naamo; Xie, Qiancheng

2017-01-01

Sediment-dynamics modeling is a useful tool for estimating a dam's lifespan and its cost-benefit analysis. Collecting real data for sediment-dynamics analysis from conventional field survey methods is both tedious and expensive. Therefore, for most rivers, the historical record of data is either missing or not very detailed. Available data and existing tools have much potential and may be used for qualitative prediction of future bathymetric change trend. This study shows that proxy approaches may be used to increase the spatiotemporal resolution of flow data, and hypothesize the river cross-sections and sediment data. Sediment-dynamics analysis of the reach of the Tenryu River upstream of Sakuma Dam in Japan was performed to predict its future bathymetric changes using a 1D numerical model (HEC-RAS). In this case study, only annually-averaged flow data and the river's longitudinal bed profile at 5-year intervals were available. Therefore, the other required data, including river cross-section and geometry and sediment inflow grain sizes, had to be hypothesized or assimilated indirectly. The model yielded a good qualitative agreement, with an R2 (coefficient of determination) of 0.8 for the observed and simulated bed profiles. A predictive simulation demonstrated that the useful life of the dam would end after the year 2035 (±5 years), which is in conformity with initial detailed estimates. The study indicates that a sediment-dynamic analysis can be performed even with a limited amount of data. However, such studies may only assess the qualitative trends of sediment dynamics.

Cost-utility and budget impact analyses of the use of NEPA for chemotherapy-induced nausea and vomiting prophylaxis in Italy.

PubMed

Restelli, Umberto; Saibene, Gabriella; Nardulli, Patrizia; Di Turi, Roberta; Bonizzoni, Erminio; Scolari, Francesca; Perrone, Tania; Croce, Davide; Celio, Luigi

2017-08-01

To evaluate the efficiency of resources allocation and sustainability of the use of netupitant+palonosetron (NEPA) for chemotherapy-induced nausea and vomiting (CINV) prophylaxis assuming the Italian National Health Service (NHS) perspective. A published Markov model was adapted to assess the incremental cost-utility ratio of NEPA compared with aprepitant (APR) + palonosetron (PALO), fosaprepitant (fAPR) + PALO, APR + ondansetron (ONDA), fAPR + ONDA in patients receiving a highly emetogenic chemotherapy (HEC) and with APR + PALO and fAPR + PALO in patients receiving a moderately emetogenic chemotherapy (MEC). Oncology hospital department in Italy. A Markov model was used to determine the impact of NEPA on the budget of the Italian NHS on a 5-day time horizon, corresponding to the acute and delayed CINV prophylaxis phases. Direct medical costs considered were related to antiemetic drugs, adverse events management, CINV episodes management. Clinical and quality of life data referred to previously published works. The budget impact analysis considered the aforementioned therapies plus PALO alone (for HEC and MEC) on a 5-year time horizon, comparing two scenarios: one considering the use of NEPA and one not considering its use. Incremental cost per quality adjusted life year (QALY) and differential economic impact for the Italian NHS between the two scenarios considered. NEPA is more effective and less expensive (dominant) compared with APR + PALO (for HEC and MEC), fAPR + PALO (for HEC and MEC), APR + ONDA (for HEC), fAPR + ONDA (for HEC). The use of NEPA would lead to a 5-year cost decrease of €63.7 million (€42.7 million for HEC and €20.9 million for MEC). NEPA allows an efficient allocation of resources for the Italian NHS and it is sustainable, leading to a cost decrease compared with a scenario which does not consider its use. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Stable and pH-responsive core-shell nanoparticles based on HEC and PMAA networks via template copolymerization

NASA Astrophysics Data System (ADS)

Zhang, Y.; Jin, Q.; Chen, Y.; Zhao, J.

2011-10-01

Taking advantage of the specific hydrogen bonding interactions, stable and pH-responsive core-shell nanoparticles based on hydroxyethyl cellulose (HEC) and polymethacrylic acid (PMAA) networks, with a < D h > size ranging from 190 to 250 nm, can be efficiently prepared via facile one-step co-polymerization of methacrylic acid (MAA) and N, N'-methylenebisacrylamide (MBA) on HEC template in water. Using dynamic light scattering, electrophoretic light scattering, fluorescence spectrometry, thermo-gravimetric analysis, TEM, and AFM observations, the influence of crosslinker MBA as well as the reaction parameters were studied. The results show that after the introduction of crosslinker MBA, the nanoparticles became less compact; their size exhibited a smaller pH sensitivity, and their stability against pH value was improved greatly. Furthermore, the size, structure, and pH response of the nanoparticles can be adjusted via varying the reaction parameters: nanoparticles of smaller size, more compact structure, and higher swelling capacity were produced as pH value of the reaction medium increased or the HEC/MAA ratio decreased; while nanoparticles of smaller size, less compact structure and smaller swelling capacity were produced as the total feeding concentration increased.

Differences in Chlamydia trachomatis Serovar E Growth Rate in Polarized Endometrial and Endocervical Epithelial Cells Grown in Three-Dimensional Culture▿

PubMed Central

Guseva, Natalia V.; Dessus-Babus, Sophie; Moore, Cheryl G.; Whittimore, Judy D.; Wyrick, Priscilla B.

2007-01-01

In vitro studies of obligate intracellular chlamydia biology and pathogenesis are highly dependent on the use of experimental models and growth conditions that mimic the mucosal architecture and environment these pathogens encounter during natural infections. In this study, the growth of Chlamydia trachomatis genital serovar E was monitored in mouse fibroblast McCoy cells and compared to more relevant host human epithelial endometrium-derived HEC-1B and cervix-derived HeLa cells, seeded and polarized on collagen-coated microcarrier beads, using a three-dimensional culture system. Microscopy analysis of these cell lines prior to infection revealed morphological differences reminiscent of their in vivo architecture. Upon infection, early chlamydial inclusion distribution was uniform in McCoy cells but patchy in both epithelial cell lines. Although no difference in chlamydial attachment to or entry into the two genital epithelial cell lines was noted, active bacterial genome replication and transcription, as well as initial transformation of elementary bodies to reticulate bodies, were detected earlier in HEC-1B than in HeLa cells, suggesting a faster growth, which led to higher progeny counts and titers in HEC-1B cells upon completion of the developmental cycle. Chlamydial development in the less relevant McCoy cells was very similar to that in HeLa cells, although higher progeny counts were obtained. In conclusion, this three-dimensional bead culture system represents an improved model for harvesting large quantities of infectious chlamydia progeny from their more natural polarized epithelial host cells. PMID:17088348

Molecular analysis of bacterial communities and detection of potential pathogens in a recirculating aquaculture system for Scophthalmus maximus and Solea senegalensis.

PubMed

Martins, Patrícia; Cleary, Daniel F R; Pires, Ana C C; Rodrigues, Ana Maria; Quintino, Victor; Calado, Ricardo; Gomes, Newton C M

2013-01-01

The present study combined a DGGE and barcoded 16S rRNA pyrosequencing approach to assess bacterial composition in the water of a recirculating aquaculture system (RAS) with a shallow raceway system (SRS) for turbot (Scophthalmus maximus) and sole (Solea senegalensis). Barcoded pyrosequencing results were also used to determine the potential pathogen load in the RAS studied. Samples were collected from the water supply pipeline (Sup), fish production tanks (Pro), sedimentation filter (Sed), biofilter tank (Bio), and protein skimmer (Ozo; also used as an ozone reaction chamber) of twin RAS operating in parallel (one for each fish species). Our results revealed pronounced differences in bacterial community composition between turbot and sole RAS, suggesting that in the systems studied there is a strong species-specific effect on water bacterial communities. Proteobacteria was the most abundant phylum in the water supply and all RAS compartments. Other important taxonomic groups included the phylum Bacteriodetes. The saltwater supplied displayed a markedly lower richness and appeared to have very little influence on bacterial composition. The following potentially pathogenic species were detected: Photobacterium damselae in turbot (all compartments), Tenacibaculum discolor in turbot and sole (all compartments), Tenacibaculum soleae in turbot (all compartments) and sole (Pro, Sed and Bio), and Serratia marcescens in turbot (Sup, Sed, Bio and Ozo) and sole (only Sed) RAS. Despite the presence of these pathogens, no symptomatic fish were observed. Although we were able to identify potential pathogens, this approach should be employed with caution when monitoring aquaculture systems, as the required phylogenetic resolution for reliable identification of pathogens may not always be possible to achieve when employing 16S rRNA gene fragments.

Molecular Analysis of Bacterial Communities and Detection of Potential Pathogens in a Recirculating Aquaculture System for Scophthalmus maximus and Solea senegalensis

PubMed Central

Martins, Patrícia; Cleary, Daniel F. R.; Pires, Ana C. C.; Rodrigues, Ana Maria; Quintino, Victor; Calado, Ricardo; Gomes, Newton C. M.

2013-01-01

The present study combined a DGGE and barcoded 16S rRNA pyrosequencing approach to assess bacterial composition in the water of a recirculating aquaculture system (RAS) with a shallow raceway system (SRS) for turbot (Scophthalmus maximus) and sole (Solea senegalensis). Barcoded pyrosequencing results were also used to determine the potential pathogen load in the RAS studied. Samples were collected from the water supply pipeline (Sup), fish production tanks (Pro), sedimentation filter (Sed), biofilter tank (Bio), and protein skimmer (Ozo; also used as an ozone reaction chamber) of twin RAS operating in parallel (one for each fish species). Our results revealed pronounced differences in bacterial community composition between turbot and sole RAS, suggesting that in the systems studied there is a strong species-specific effect on water bacterial communities. Proteobacteria was the most abundant phylum in the water supply and all RAS compartments. Other important taxonomic groups included the phylum Bacteriodetes. The saltwater supplied displayed a markedly lower richness and appeared to have very little influence on bacterial composition. The following potentially pathogenic species were detected: Photobacterium damselae in turbot (all compartments), Tenacibaculum discolor in turbot and sole (all compartments), Tenacibaculum soleae in turbot (all compartments) and sole (Pro, Sed and Bio), and Serratia marcescens in turbot (Sup, Sed, Bio and Ozo) and sole (only Sed) RAS. Despite the presence of these pathogens, no symptomatic fish were observed. Although we were able to identify potential pathogens, this approach should be employed with caution when monitoring aquaculture systems, as the required phylogenetic resolution for reliable identification of pathogens may not always be possible to achieve when employing 16S rRNA gene fragments. PMID:24278329

Molecular Dynamics Simulations and Dynamic Network Analysis Reveal the Allosteric Unbinding of Monobody to H-Ras Triggered by R135K Mutation.

PubMed

Ni, Duan; Song, Kun; Zhang, Jian; Lu, Shaoyong

2017-10-26

Ras proteins, as small GTPases, mediate cell proliferation, survival and differentiation. Ras mutations have been associated with a broad spectrum of human cancers and thus targeting Ras represents a potential way forward for cancer therapy. A recently reported monobody NS1 allosterically disrupts the Ras-mediated signaling pathway, but its efficacy is reduced by R135K mutation in H-Ras. However, the detailed mechanism is unresolved. Here, using molecular dynamics (MD) simulations and dynamic network analysis, we explored the molecular mechanism for the unbinding of NS1 to H-Ras and shed light on the underlying allosteric network in H-Ras. MD simulations revealed that the overall structures of the two complexes did not change significantly, but the H-Ras-NS1 interface underwent significant conformational alteration in the mutant Binding free energy analysis showed that NS1 binding was unfavored after R135K mutation, which resulted in the unfavorable binding of NS1. Furthermore, the critical residues on H-Ras responsible for the loss of binding of NS1 were identified. Importantly, the allosteric networks for these important residues were revealed, which yielded a novel insight into the allosteric regulatory mechanism of H-Ras.

Computer Operations Study of Reservoir Operations for Six Mississippi River Headwaters Dams. Appendix A.

DTIC Science & Technology

1982-06-01

p*A C.._ _ __ _ _ A, d.tibutiou is unhimta 4 iit 84~ L0 TABLE OF CONTENTS APPENDIX SCOPE OF WORK B MERGE AND COST PROGRAM DOCUMENTATION C FATSCO... PROGRAM TO COMPUTE TIME SERIES FREQUENCY RELATIONSHIPS D HEC-DSS - TIME SERIES DATA FILE MANAGEMENT SYSTEM E PLAN 1 -TIM SERIES DATA PLOTS AND ANNUAL...University of Minnesota, utilized an early version of the Hydrologic Engineering * Center’s (HEC) EEC-5c Computer Program . EEC is a Corps of Engineers

Flood Frequency Analysis using different flood descriptors - the Warsaw reach of the river Vistula case study

NASA Astrophysics Data System (ADS)

Karamuz, Emilia; Kochanek, Krzysztof; Romanowicz, Renata

2014-05-01

Flood frequency analysis (FFA) is customarily performed using annual maximum flows. However, there is a number of different flood descriptors that could be used. Among them are water levels, peaks over the threshold, flood-wave duration, flood volume, etc. In this study we compare different approaches to FFA for their suitability for flood risk assessment. The main goal is to obtain the FFA curve with the smallest possible uncertainty limits, in particular for the distribution tail. The extrapolation of FFA curves is crucial in future flood risk assessment in a changing climate. We compare the FFA curves together with their uncertainty limits obtained using flows, water levels, flood inundation area and volumes for the Warsaw reach of the river Vistula. Moreover, we derive the FFA curves obtained using simulated flows. The results are used to derive the error distribution for the maximum simulated and observed values under different modelling techniques and assess its influence on flood risk predictions for ungauged catchments. MIKE11, HEC-RAS and transfer function model are applied in average and extreme conditions to model flow propagation in the Warsaw Vistula reach. The additional questions we want to answer are what is the range of application of different modelling tools under various flow conditions and how can the uncertainty of flood risk assessment be decreased. This work was partly supported by the projects "Stochastic flood forecasting system (The River Vistula reach from Zawichost to Warsaw)" and "Modern statistical models for analysis of flood frequency and features of flood waves", carried by the Institute of Geophysics, Polish Academy of Sciences on the order of the National Science Centre (contracts Nos. 2011/01/B/ST10/06866 and 2012/05/B/ST10/00482, respectively). The water level and flow data were provided by the Institute of Meteorology and Water Management (IMGW), Poland.

Impact of The Protective Renin-Angiotensin System (RAS) on The Vasoreparative Function of CD34+ CACs in Diabetic Retinopathy

NASA Technical Reports Server (NTRS)

Duan, Yaqian; Moldovan, Leni; Miller, Rehae C.; Beli, Eleni; Salazar, Tatiana; Hazra, Sugata; Al-Sabah, Jude; Chalam, KV; Raghunandan, Sneha; Vyas, Ruchi;

Potentiality of rainwater harvesting for an urban community in Bangladesh

NASA Astrophysics Data System (ADS)

Akter, Aysha; Ahmed, Shoukat

2015-09-01

Due to cost effectiveness, rainwater harvesting (RWH) systems are practicing already in some rural parts of Bangladesh but very few in urban areas. This paper aimed to evaluate the potentiality of RWH systems in the South Agrabad in Chittagong city with an average annual precipitation of 3000 mm, experiencing both water scarcity and urban flooding in the same year. The adopted approach was Analytic Hierarchy Process (AHP) based multicriteria decision analysis technique, and the evaluation criteria were roof area, slope, drainage density and runoff coefficient. Geospatial Hydrologic Modeling Extension supported hydrologic model viz. HEC-HMS used to simulate the precipitation-runoff process, the model outcomes showed RWH potentiality which could minimize stagnant storm water up to 26% through supplementing city water supply annually up to 20 liter/person/day. Then, assigning suitable weightage to the evaluation criteria with their associated features in ArcGIS 9.3, the study area was reasonably divided into three potential zones i.e. good, moderate and poor covering 19%, 64% and 17% of the total area respectively. Thus, this is envisaged AHP using HEC-HMS could provide important guidance to the decision supporting system not only for urban areas but also for the wide sub-basin/basin context.

Flood Hazard Mapping Assessment for El-Awali River Catchment-Lebanon

NASA Astrophysics Data System (ADS)

Hdeib, Rouya; Abdallah, Chadi; Moussa, Roger; Hijazi, Samar

2016-04-01

River flooding prediction and flood forecasting has become an essential stage in the major flood mitigation plans worldwide. Delineation of floodplains resulting from a river flooding event requires coupling between a Hydrological rainfall-runoff model to calculate the resulting outflows of the catchment and a hydraulic model to calculate the corresponding water surface profiles along the river main course. In this study several methods were applied to predict the flood discharge of El-Awali River using the available historical data and gauging records and by conducting several site visits. The HEC-HMS Rainfall-Runoff model was built and applied to calculate the flood hydrographs along several outlets on El-Awali River and calibrated using the storm that took place on January 2013 and caused flooding of the major Lebanese rivers and by conducting additional site visits to calculate proper river sections and record witnesses of the locals. The Hydraulic HEC-RAS model was then applied to calculate the corresponding water surface profiles along El-Awali River main reach. Floodplain delineation and Hazard mapping for 10,50 and 100 years return periods was performed using the Watershed Modeling System WMS. The results first show an underestimation of the flood discharge recorded by the operating gauge stations on El-Awali River, whereas, the discharge of the 100 years flood may reach up to 506 m3/s compared by lower values calculated using the traditional discharge estimation methods. Second any flooding of El-Awali River may be catastrophic especially to the coastal part of the catchment and can cause tragic losses in agricultural lands and properties. Last a major floodplain was noticed in Marj Bisri village this floodplain can reach more than 200 meters in width. Overall, performance was good and the Rainfall-Runoff model can provide valuable information about flows especially on ungauged points and can perform a great aid for the floodplain delineation and flood prediction methods in poorly gauged basins, but further model updates and calibration is always required to compensate the weaknesses in such model and attain better results.

Mapping the functional versatility and fragility of Ras GTPase signaling circuits through in vitro network reconstitution.

PubMed

Coyle, Scott M; Lim, Wendell A

2016-01-14

The Ras-superfamily GTPases are central controllers of cell proliferation and morphology. Ras signaling is mediated by a system of interacting molecules: upstream enzymes (GEF/GAP) regulate Ras's ability to recruit multiple competing downstream effectors. We developed a multiplexed, multi-turnover assay for measuring the dynamic signaling behavior of in vitro reconstituted H-Ras signaling systems. By including both upstream regulators and downstream effectors, we can systematically map how different network configurations shape the dynamic system response. The concentration and identity of both upstream and downstream signaling components strongly impacted the timing, duration, shape, and amplitude of effector outputs. The distorted output of oncogenic alleles of Ras was highly dependent on the balance of positive (GAP) and negative (GEF) regulators in the system. We found that different effectors interpreted the same inputs with distinct output dynamics, enabling a Ras system to encode multiple unique temporal outputs in response to a single input. We also found that different Ras-to-GEF positive feedback mechanisms could reshape output dynamics in distinct ways, such as signal amplification or overshoot minimization. Mapping of the space of output behaviors accessible to Ras provides a design manual for programming Ras circuits, and reveals how these systems are readily adapted to produce an array of dynamic signaling behaviors. Nonetheless, this versatility comes with a trade-off of fragility, as there exist numerous paths to altered signaling behaviors that could cause disease.

RNA interference of pax2 inhibits growth of transplanted human endometrial cancer cells in nude mice

PubMed Central

Zhang, Li-Ping; Shi, Xiao-Yan; Zhao, Chang-Yin; Liu, Yong-Zhen; Cheng, Ping

2011-01-01

The development of human endometrial carcinoma (HEC) is a complex pathologic process involves several oncogenes and tumor suppressor genes. The full-length paired-box gene 2 (pax2), a recently discovered Oncogene, promotes cell proliferation and growth and inhibits apoptosis of HEC cells. Here, we examined the effect of pax2 small interfering RNA (siRNA) on the growth of transplanted HEC cells in nude mice. The expression of Pax2 in 21 cases of normal endometrium and 38 cases of HEC was examined by immohistochemistry (IHC). HEC models were developed by subcutaneously transferring HEC cells into nude mice, followed by treatment with empty lentivirus vector, lentivirus vector-based pax2 siRNA, and phosphate buffered saline, respectively. Four weeks later, tumor size was measured, tumor inhibition rate was calculated, and histological analyses were conducted after staining with hematoxylin and eosin. The expression of Pax2 and Bcl-2 was detected by Western blot; proliferating cell nuclear antigen (PCNA) was detected by IHC. Significant differences were observed in the positive rate of Pax2 between normal endometrium and HEC (14.2% vs. 60.5%, P < 0.01). The expression index of Pax2 in well differentiated tumors was 1.88 ± 1.68, much lower than that in tumors of moderate (3.07 ± 1.96, P < 0.05) or poor differentiation (5.45 ± 2.76, P < 0.01). Tumor necrosis increased, nuclear basophilia stain decreased, tumor growth was inhibited, and PCNA, Pax2, and Bcl-2 expression was reduced in HEC models treated with pax2 siRNA. These results indicate that Pax2 expression is related to HEC tumor biology with the increased expression of Pax2 correlated to malignancy. pax2 siRNA down-regulates Pax2 expression and inhibits tumorigenesis of HEC in nude mice, possibly due to cell apoptosis and the inhibition of tumor proliferation induced by down-regulation of Bcl-2. PMID:21627862

Flood hydrology and dam-breach hydraulic analyses of four reservoirs in the Black Hills, South Dakota

USGS Publications Warehouse

Hoogestraat, Galen K.

2011-01-01

Extensive information about the construction of dams or potential downstream hazards in the event of a dam breach is not available for many small reservoirs within the Black Hills National Forest. In 2009, the U.S. Forest Service identified the need for reconnaissance-level dam-breach assessments for four of these reservoirs within the Black Hills National Forest (Iron Creek, Horsethief, Lakota, and Mitchell Lakes) with the potential to flood downstream structures. Flood hydrology and dam-breach hydraulic analyses for the four selected reservoirs were conducted by the U.S. Geological Survey in cooperation with the U.S. Forest service to estimate the areal extent of downstream inundation. Three high-flow breach scenarios were considered for cases when the dam is in place (overtopped) and when a dam break (failure) occurs: the 100-year recurrence 24-hour precipitation, 500-year recurrence peak flow, and the probable maximum precipitation. Inundation maps were developed that show the estimated extent of downstream floodwaters from simulated scenarios. Simulation results were used to determine the hazard classification of a dam break (high, significant, or low), based primarily on the potential for loss of life or property damage resulting from downstream inundation because of the flood surge.The inflow design floods resulting from the two simulated storm events (100-year 24-hour and probable maximum precipitation) were determined using the U.S. Army Corps of Engineers Hydrologic Engineering Center Hydrologic Modeling System (HEC-HMS). The inflow design flood for the 500-year recurrence peak flow was determined by using regional regression equations developed for streamflow-gaging stations with similar watershed characteristics. The step-backwater hydraulic analysis model, Hydrologic Engineering Center's River Analysis System (HEC-RAS), was used to determine water-surface profiles of in-place and dam-break scenarios for the three inflow design floods that were simulated. Inundation maps for in-place and dam-break scenarios were developed for the area downstream from the dam to the mouth of each stream.Dam-break scenarios for three of the four reservoirs assessed in this study were rated as low hazards owing to absence of permanent structures downstream from the dams. Iron Creek Lake's downstream channel to its mouth does not include any permanent structures within the inundation flood plains. For the two reservoirs with the largest watershed areas, Lakota and Mitchell Lake, the additional floodwater surge resulting from a dam break would be minor relative to the magnitude of the large flood streamflow into the reservoirs, based on the similar areal extent of inundation for the in-place and dam-break scenarios as indicated by the developed maps. A dam-break scenario at Horsethief Lake is rated as a significant hazard because of potential lives-in-jeopardy in downstream dwellings and appreciable economic loss.

Effects of dexamethasone-21-isonicotinate on peripheral insulin action in dairy cows 5 days after surgical correction of abomasal displacement.

PubMed

Kusenda, M; Kaske, M; Piechotta, M; Locher, L; Starke, A; Huber, K; Rehage, J

2013-01-01

Dexamethasone frequently is used for treatment of ketosis in dairy cows, but its effects are not fully understood. Dexamethasone treatment affects whole body insulin sensitivity. Twelve German Holstein cows, 2-4 weeks postpartum, 5 days after omentopexy to correct left abomasal displacement. Randomized, blinded, case-control study. Treatment with dexamethasone-21-isonicotinate (DG; 40 μg/kg IM; n = 6) or saline (control group [CG], 15 mL IM, n = 6) on day 0 (d0). Blood samples were obtained before (d0) and after treatment (d1 and d2), and analyzed for glucose, insulin, and nonesterified fatty acid (NEFA) concentrations. Hepatic triglycerides (TAG) were measured in liver samples taken on d0 and d2. Five consecutive hyperinsulinemic-euglycemic clamps (HEC-I-V; insulin dosages: 0.1, 0.5, 2, 5, 10 mU/kg/min, respectively) were performed on d1 and steady state glucose infusion rate (SSGIR), insulin concentration (SSIC), insulin sensitivity index (ISI = SSGIR/SSIC), and plasma NEFA concentration (SSNEFA) were assessed. Compared with CG-cows, DG-cows on d1 had higher plasma glucose (P = .004) and insulin (P < .001) concentrations, decreased SSGIR (HEC-II, P = .002; HEC-IV, P = .033), ISI (HEC-I, P < .015; HEC-II, P = .004), and insulin-stimulated decrease in SSNEFA (HEC-II, P = .006; HEC-III, P = .01; HEC-IV, P = .003; HEC-V, P = .011). Decrease in hepatic TAG content in DG-cows was higher compared with CG-cows (P < .001). Dexamethasone decreases whole body insulin sensitivity and affects glucose and lipid metabolism in early lactating dairy cows. Copyright © 2012 by the American College of Veterinary Internal Medicine.

Application of Virtual Rain and Stream Gauge Information Service for Improved Flood Early Warning System in Lower Mekong Countries

NASA Astrophysics Data System (ADS)

Basnayake, S. B.; Jayasinghe, S.; Meechaiya, C.; Markert, K. N.; Lee, H.; Towashiraporn, P.; Anderson, E.; Okeowo, M. A.

2017-12-01

Asia is the most vulnerable region in the world to hydro-meteorological extreme events, exacerbated by climate variability and change. Impacts of floods have been on the rapid increase in the recent decades. Myanmar is one of the most vulnerable countries in the lower Mekong region due to its socioeconomic situation (eg; Nargis in 2008, monsoon floods in 2015, etc). Early warning is an effective way to prepare for hydro-meteorological hazards, to minimize disaster risks; however, early warning systems in Myanmar are seriously hampered by limited observation networks. The Virtual Rain and Stream Gauge Information Service (VRSGIS) has been developed by SERVIR-Mekong program of Asian Disaster Preparedness Center (ADPC) to address these gaps and to provide dense, satellite-based rainfall and water level data, which are calibrated and validated with available in-situ observations. This service would enhance decision making in lower Mekong countries, including Myanmar, to minimize impacts of impending disasters. This service contains rainfall data from GPM IMERG and GSMap, CMORPH, TRMM, and CHIRPS, and water levels for 15 locations using Jason-2/3 altimetry. The virtual daily rainfall data sets are being calibrated with Gamma distribution method and are made publicly accessible through a user-friendly web interface.This paper presents a case study of satellite-derived rainfall data accessed from VRSGIS for hydrological modeling in Myanmar, to estimate inundation areas in Kalay township area of Chindwin River basin during the country's worst flood in 2015. Twelve out of fourteen States of Myanmar were severely affected, 103 people were killed, and one million were displaced due to heavy rains associated with Komen cyclone. The aforementioned rainfall data products are used as inputs for HEC-HMS hydrological runoff model to calculate river flows along Chindwin River, and HEC-RAS hydraulic model is used to estimate inundation areas in downstream including Kalay township area. Model results (inundations) are compared with the estimates of water levels of Jason 2/3 measurements from two locations along the river. The results encourage us to use satellite-derived rainfall data over upstream areas to improve flood modeling, which contributes to improved flood early warning in Myanmar and other lower Mekong countries.

Exploring the interactions of the RAS family in the human protein network and their potential implications in RAS-directed therapies

PubMed Central

Bueno, Anibal; Morilla, Ian; Diez, Diego; Moya-Garcia, Aurelio A.; Lozano, José; Ranea, Juan A.G.

2016-01-01

RAS proteins are the founding members of the RAS superfamily of GTPases. They are involved in key signaling pathways regulating essential cellular functions such as cell growth and differentiation. As a result, their deregulation by inactivating mutations often results in aberrant cell proliferation and cancer. With the exception of the relatively well-known KRAS, HRAS and NRAS proteins, little is known about how the interactions of the other RAS human paralogs affect cancer evolution and response to treatment. In this study we performed a comprehensive analysis of the relationship between the phylogeny of RAS proteins and their location in the protein interaction network. This analysis was integrated with the structural analysis of conserved positions in available 3D structures of RAS complexes. Our results show that many RAS proteins with divergent sequences are found close together in the human interactome. We found specific conserved amino acid positions in this group that map to the binding sites of RAS with many of their signaling effectors, suggesting that these pairs could share interacting partners. These results underscore the potential relevance of cross-talking in the RAS signaling network, which should be taken into account when considering the inhibitory activity of drugs targeting specific RAS oncoproteins. This study broadens our understanding of the human RAS signaling network and stresses the importance of considering its potential cross-talk in future therapies. PMID:27713118

Continuous hydrologic simulation and flood-frequency, hydraulic, and flood-hazard analysis of the Blackberry Creek watershed, Kane County, Illinois

USGS Publications Warehouse

Soong, David T.; Straub, Timothy D.; Murphy, Elizabeth A.

2006-01-01

Results of hydrologic model, flood-frequency, hydraulic model, and flood-hazard analysis of the Blackberry Creek watershed in Kane County, Illinois, indicate that the 100-year and 500-year flood plains range from approximately 25 acres in the tributary F watershed (a headwater subbasin at the northeastern corner of the watershed) to almost 1,800 acres in Blackberry Creek main stem. Based on 1996 land-cover data, most of the land in the 100-year and 500-year flood plains was cropland, forested and wooded land, and grassland. A relatively small percentage of urban land was in the flood plains. The Blackberry Creek watershed has undergone rapid urbanization in recent decades. The population and urbanized lands in the watershed are projected to double from the 1990 condition by 2020. Recently, flood-induced damage has occurred more frequently in urbanized areas of the watershed. There are concerns about the effect of urbanization on flood peaks and volumes, future flood-mitigation plans, and potential effects on the water quality and stream habitats. This report describes the procedures used in developing the hydrologic models, estimating the flood-peak discharge magnitudes and recurrence intervals for flood-hazard analysis, developing the hydraulic model, and the results of the analysis in graphical and tabular form. The hydrologic model, Hydrological Simulation Program-FORTRAN (HSPF), was used to perform the simulation of continuous water movements through various patterns of land uses in the watershed. Flood-frequency analysis was applied to an annual maximum series to determine flood quantiles in subbasins for flood-hazard analysis. The Hydrologic Engineering Center-River Analysis System (HEC-RAS) hydraulic model was used to determine the 100-year and 500-year flood elevations, and to determine the 100-year floodway. The hydraulic model was calibrated and verified using high water marks and observed inundation maps for the July 17-18, 1996, flood event. Digital maps of the 100-year and 500-year flood plains and the 100-year floodway for each tributary and the main stem of Blackberry Creek were compiled.

Intestinal Targeting of Ganciclovir Release Employing a Novel HEC-PAA Blended Lyomatrix.

PubMed

Mabrouk, Mostafa; Mulla, Jameel A S; Kumar, Pradeep; Chejara, Dharmesh R; Badhe, Ravindra V; Choonara, Yahya E; du Toit, Lisa C; Pillay, Viness

2016-10-01

A hydroxyethylcellulose-poly(acrylic acid) (HEC-PAA) lyomatrix was developed for ganciclovir (GCV) intestine targeting to overcome its undesirable degradation in the stomach. GCV was encapsulated within the HEC-PAA lyomatrix prepared by lyophilization. Conventional tablets were also prepared with identical GCV concentrations in order to compare the GCV release behavior from the lyomatrix and tablets. GCV incorporation (75.12%) was confirmed using FTIR, DSC, and TGA. The effect of GCV loading on the microstructure properties of the lyomatrix was evaluated by SEM, AFM, and BET surface area measurements. The in vitro drug release study showed steady and rapid release profiles from the GCV-loaded lyomatrix compared with the tablet formulation at identical pH values. Minimum GCV release was observed at acidic pH (≤40%) and maximum release occurred at intestinal pH values (≥90%) proving the intestinal targeting ability of the lyomatrix. Kinetic modeling revealed that the GCV-loaded lyomatrix exhibited zero-order release kinetics (n = 1), while the tablets were best described via the Peppas model. Textural analysis highlighted enhanced matrix resilience and rigidity gradient (12.5%, 20 Pa) for the GCV-loaded lyomatrix compared to the pure (7%, 9.5 Pa) HEC-PAA lyomatrix. Bench-top MRI imaging was used to confirm the mechanism of GCV release behavior by monitoring the swelling and erosion rates. The swelling and erosion rate of the tablets was not sufficient to achieve rapid zero-order GCV release as with the lyomatrix. These combined results suggest that the HEC-PAA lyomatrix may be suitable for GCV intestinal targeting after oral administration.

The Affordable Medicines Facility-malaria (AMFm): are remote areas benefiting from the intervention?

PubMed

Ye, Yazoume; Arnold, Fred; Noor, Abdisalan; Wamukoya, Marilyn; Amuasi, John; Blay, Samuel; Mberu, Blessing; Ren, Ruilin; Kyobutungi, Catherine; Wekesah, Frederick; Gatakaa, Hellen; Toda, Mitsuru; Njogu, Julius; Evance, Illah; O'Connell, Kathryn; Shewchuk, Tanya; Thougher, Sarah; Mann, Andrea; Willey, Barbara; Goodman, Catherine; Hanson, Kara

2015-10-09

To assess the availability, price and market share of quality-assured artemisinin-based combination therapy (QAACT) in remote areas (RAs) compared with non-remote areas (nRAs) in Kenya and Ghana at end-line of the Affordable Medicines Facility-malaria (AMFm) intervention. Areas were classified by remoteness using a composite index computed from estimated travel times to three levels of service centres. The index was used to five categories of remoteness, which were then grouped into two categories of remote and non-remote areas. The number of public or private outlets with the potential to sell or distribute anti-malarial medicines, screened in nRAs and RAs, respectively, was 501 and 194 in Ghana and 9980 and 2353 in Kenya. The analysis compares RAs with nRAs in terms of availability, price and market share of QAACT in each country. QAACT were similarly available in RAs as nRAs in Ghana and Kenya. In both countries, there was no statistical difference in availability of QAACT with AMFm logo between RAs and nRAs in public health facilities (PHFs), while private-for-profit (PFP) outlets had lower availability in RA than in nRAs (Ghana: 66.0 vs 82.2 %, p < 0.0001; Kenya: 44.9 vs 63.5 %, p = <0.0001. The median price of QAACT with AMFm logo for PFP outlets in RAs (USD1.25 in Ghana and USD0.69 in Kenya) was above the recommended retail price in Ghana (US$0.95) and Kenya (US$0.46), and much higher than in nRAs for both countries. QAACT with AMFm logo represented the majority of QAACT in RAs and nRAs in Kenya and Ghana. In the PFP sector in Ghana, the market share for QAACT with AMFm logo was significantly higher in RAs than in nRAs (75.6 vs 51.4 %, p < 0.0001). In contrast, in similar outlets in Kenya, the market share of QAACT with AMFm logo was significantly lower in RAs than in nRAs (39.4 vs 65.1 %, p < 0.0001). The findings indicate the AMFm programme contributed to making QAACT more available in RAs in these two countries. Therefore, the AMFm approach can inform other health interventions aiming at reaching hard-to-reach populations, particularly in the context of universal access to health interventions. However, further examination of the factors accounting for the deep penetration of the AMFm programme into RAs is needed to inform actions to improve the healthcare delivery system, particularly in RAs.

Moral Reasoning among HEC Members: An Empirical Evaluation of the Relationship of Theory and Practice in Clinical Ethics Consultation.

PubMed

Wasserman, Jason Adam; Stevenson, Shannon Lindsey; Claxton, Cassandra; Krug, Ernest F

2015-01-01

In light of the ongoing development and implementation of core competencies in bioethics, it is important to proceed with a clear sense of how bioethics knowledge is utilized in the functioning of hospital ethics committees (HECs). Without such an understanding, we risk building a costly edifice on a foundation that is ambiguous at best. This article examines the empirical relationship between traditional paradigms of bioethics theory and actual decision making by HEC members using survey data from HEC members. The assumption underlying the standardization of qualifications and corresponding call for increased education of HEC members is that they will base imminent case decisions on inculcated knowledge. Our data suggest, however, that HEC members first decide intuitively and then look for justification, thereby highlighting the need to re-examine the pedagogical processes of ethics education in the process of standardizing and improving competencies. Copyright 2015 The Journal of Clinical Ethics. All rights reserved.

Molecular Dynamics Simulations and Dynamic Network Analysis Reveal the Allosteric Unbinding of Monobody to H-Ras Triggered by R135K Mutation

PubMed Central

Song, Kun; Zhang, Jian; Lu, Shaoyong

2017-01-01

Ras proteins, as small GTPases, mediate cell proliferation, survival and differentiation. Ras mutations have been associated with a broad spectrum of human cancers and thus targeting Ras represents a potential way forward for cancer therapy. A recently reported monobody NS1 allosterically disrupts the Ras-mediated signaling pathway, but its efficacy is reduced by R135K mutation in H-Ras. However, the detailed mechanism is unresolved. Here, using molecular dynamics (MD) simulations and dynamic network analysis, we explored the molecular mechanism for the unbinding of NS1 to H-Ras and shed light on the underlying allosteric network in H-Ras. MD simulations revealed that the overall structures of the two complexes did not change significantly, but the H-Ras–NS1 interface underwent significant conformational alteration in the mutant Binding free energy analysis showed that NS1 binding was unfavored after R135K mutation, which resulted in the unfavorable binding of NS1. Furthermore, the critical residues on H-Ras responsible for the loss of binding of NS1 were identified. Importantly, the allosteric networks for these important residues were revealed, which yielded a novel insight into the allosteric regulatory mechanism of H-Ras. PMID:29072601

Opening the black box of ethics policy work: evaluating a covert practice.

PubMed

Frolic, Andrea; Drolet, Katherine; Bryanton, Kim; Caron, Carole; Cupido, Cynthia; Flaherty, Barb; Fung, Sylvia; McCall, Lori

2012-01-01

Hospital ethics committees (HECs) and ethicists generally describe themselves as engaged in four domains of practice: case consultation, research, education, and policy work. Despite the increasing attention to quality indicators, practice standards, and evaluation methods for the other domains, comparatively little is known or published about the policy work of HECs or ethicists. This article attempts to open the "black box" of this health care ethics practice by providing two detailed case examples of ethics policy reviews. We also describe the development and application of an evaluation strategy to assess the quality of ethics policy review work, and to enable continuous improvement of ethics policy review processes. Given the potential for policy work to impact entire patient populations and organizational systems, it is imperative that HECs and ethicists develop clearer roles, responsibilities, procedural standards, and evaluation methods to ensure the delivery of consistent, relevant, and high-quality ethics policy reviews.

Resistance and resilience of small-scale recirculating aquaculture systems (RAS) with or without algae to pH perturbation

PubMed Central

Giatsis, Christos; Md Yusoff, Fatimah; Verreth, Johan; Verdegem, Marc

2018-01-01

The experimental set-up of this study mimicked recirculating aquaculture systems (RAS) where water quality parameters such as dissolved oxygen, pH, temperature, and turbidity were controlled and wastes produced by fish and feeding were converted to inorganic forms. A key process in the RAS was the conversion of ammonia to nitrite and nitrite to nitrate through nitrification. It was hypothesized that algae inclusion in RAS would improve the ammonia removal from the water; thereby improving RAS water quality and stability. To test this hypothesis, the stability of the microbiota community composition in a freshwater RAS with (RAS+A) or without algae (RAS-A) was challenged by introducing an acute pH drop (from pH 7 to 4 during three hours) to the system. Stigeoclonium nanum, a periphytic freshwater microalga was used in this study. No significant effect of the algae presence was found on the resistance to the acute pH drop on ammonia conversion to nitrite and nitrite conversion to nitrate. Also the resilience of the ammonia conversion to the pH drop disruption was not affected by the addition of algae. This could be due to the low biomass of algae achieved in the RAS. However, with regard to the conversion step of nitrite to nitrate, RAS+A was significantly more resilient than RAS-A. In terms of overall bacterial communities, the composition and predictive function of the bacterial communities was significantly different between RAS+A and RAS-A. PMID:29659617

The Evolution of American Hospital Ethics Committees: A Systematic Review.

PubMed

Courtwright, Andrew; Jurchak, Martha

2016-01-01

During the 1970s and 1980s, legal precedent, governmental recommendations, and professional society guidelines drove the formation of hospital ethics committees (HECs). The Joint Commission on Accreditation of Health Care Organization's requirements in the early 1990s solidified the role of HECs as the primary mechanism to address ethical issues in patient care. Because external factors drove the rapid growth of HECs on an institution-by-institution basis, however, no initial consensus formed around the structure and function of these committees. There are now almost 40 years of empirical studies on the composition, administration, and activities of HECs in the United States. We conducted a systematic review of the available empirical literature on HECs to describe their evolution. As HECs changed over time, they increased their total number of members and percentage of members from nursing and the community. Although physicians increasingly chaired these committees, their presence as a percentage of overall members declined. The percentage of administrative members remained steady, although committees became increasingly likely to have at least one administrative member. HECs were also increasingly likely to report to an administrative body or to the board of trustees or directors rather than to the medical staff. Finally, consultation volume increased steadily over time. There has not, however, been a national survey of the composition of ethics committees, their administration, or volume of consultation in more than 10 years, despite increasing calls for professional standards and quality improvement assessments among HECs. Copyright 2016 The Journal of Clinical Ethics. All rights reserved.

Using HEC-HMS: Application to Karkheh river basin

USDA-ARS?s Scientific Manuscript database

This paper aims to facilitate the use of HEC-HMS model using a systematic event-based technique for manual calibration of soil moisture accounting and snowmelt degree-day parameters. Manual calibration, which helps ensure the HEC-HMS parameter values are physically-relevant, is often a time-consumin...

Expression of renin–angiotensin system components in the early bovine embryo

PubMed Central

Pijacka, Wioletta; Hunter, Morag G; Broughton Pipkin, Fiona; Luck, Martin R

2012-01-01

The renin–angiotensin system (RAS), mainly associated with the regulation of blood pressure, has been recently investigated in female reproductive organs and the developing foetus. Angiotensin II (Ang II) influences oviductal gamete movements and foetal development, but there is no information about RAS in the early embryo. The aim of this study was to determine whether RAS components are present in the pre-implantation embryo, to determine how early they are expressed and to investigate their putative role at this stage of development. Bovine embryos produced in vitro were used for analysis of RAS transcripts (RT-PCR) and localisation of the receptors AGTR1 and AGTR2 (immunofluorescent labelling). We also investigated the effects of Ang II, Olmesartan (AGTR1 antagonist) and PD123319 (AGTR2 antagonist) on oocyte cleavage, embryo expansion and hatching. Pre-implanted embryos possessed AGTR1 and AGTR2 but not the other RAS components. Both receptors were present in the trophectoderm and in the inner cell mass of the blastocyst. AGTR1 was mainly localised in granular-like structures in the cytoplasm, suggesting its internalisation into clathrin-coated vesicles, and AGTR2 was found mainly in the nuclear membrane and in the mitotic spindle of dividing trophoblastic cells. Treating embryos with PD123319 increased the proportion of hatched embryos compared with the control. These results, the first on RAS in the early embryo, suggest that the pre-implanted embryo responds to Ang II from the mother rather than from the embryo itself. This may be a route by which the maternal RAS influences blastocyst hatching and early embryonic development. PMID:23781300

Extent of areal inundation of riverine wetlands along Cypress Creek and the Peace, Alafia, North Prong Alafia, and South Prong Alafia Rivers, west-central Florida

USGS Publications Warehouse

Lewelling, B.R.

2003-01-01

Riverine and palustrine system wetlands are a major ecological component of river basins in west-central Florida. Healthy wetlands are dependent upon the frequency and duration of periodic flooding or inundation. This report assesses the extent, area, depth, frequency, and duration of periodic flooding and the effects of potential surface-water withdrawals on the wetlands along Cypress Creek and the Peace, Alafia, North Prong Alafia, and South Prong Alafia Rivers. Results of the study were derived from step-backwater analysis performed at each of the rivers using the U.S. Army Corps of Engineers Hydrologic Engineering Center-River Analysis System (HEC-RAS) one-dimensional model. The step-backwater analysis was performed using selected daily mean discharges at the 10th, 50th, 70th, 80th, 90th, 98th, 99.5th, and 99.9th percentiles to compute extent of areal inundation, area of inundation, and hydraulic depth to assess the net reduction of areal inundation if 10 percent of the total river flow were diverted for potential withdrawals. The extent of areal inundation is determined by cross-sectional topography and the degree to which the channel is incised. Areal inundation occurs along the broad, low relief of the Cypress Creek floodplain during all selected discharge percentiles. However, areal inundation of the Peace and Alafia Rivers floodplains, which generally have deeply incised channels, occurs at or above discharges at the 80th percentile. The greatest area of inundation along the three rivers generally occurs between the 90th and 98th percentile discharges. The decrease in inundated area resulting from a potential 10-percent withdrawal in discharge ranged as follows: Cypress Creek, 22 to 395 acres (1.7 to 8.4 percent); Peace River, 17 to 1,900 acres (2.1 to 13.6 percent); Alafia River, 1 to 90 acres (1 to 19.6 percent); North Prong Alafia River, 1 to 46 acres (0.7 to 23.4 percent); and South Prong Alafia River, 1 to 75 acres (1.5 to 13.4 percent).

Multi-Hazard Assessment of Scour Damaged Bridges with UAS-Based Measurements

NASA Astrophysics Data System (ADS)

Özcan, O.; Ozcan, O.

2017-12-01

Flood and stream induced scour occurring in bridge piers constructed on rivers is one of the mostly observed failure reasons in bridges. Scour induced failure risk in bridges and determination of the alterations in bridge safety under seismic effects has the ultimate importance. Thus, for the determination of bridge safety under the scour effects, the scour amount under bridge piers should be designated realistically and should be tracked and updated continuously. Hereby, the scour induced failures in bridge foundation systems will be prevented and bridge substructure design will be conducted safely. In this study, in order to measure the amount of scour in bridge load bearing system (pile foundations and pile abutments) and to attain very high definition 3 dimensional models of river flood plain for the flood analysis, unmanned aircraft system (UAS) based measurement methods were implemented. UAS based measurement systems provide new and practical approach and bring high precision and reliable solutions considering recent measurement systems. For this purpose, the reinforced concrete (RC) bridge that is located on Antalya Boğaçayı River, Turkey and that failed in 2003 due to flood-induced scour was selected as the case study. The amount of scour occurred in bridge piers and piles was determined realistically and the behavior of bridge piers under scour effects was investigated. Future flood effects and the resultant amount of scour was determined with HEC-RAS software by using digital surface models that were obtained at regular intervals using UAS for the riverbed. In the light of the attained scour measurements and expected scour after a probable flood event, the behavior of scour damaged RC bridge was investigated by pushover and time history analyses under lateral and vertical seismic loadings. In the analyses, the load and displacement capacity of bridge was observed to diminish significantly under expected scour. Thus, the deterioration in multi hazard performance of the bridge was monitored significantly in the light of updated bridge load bearing system capacity. Regarding the case study, UAS based and continuously updated bridge multi hazard risk detection system was established that can be used for bridges located on riverbed.

Surface-modified anodic aluminum oxide membrane with hydroxyethyl celluloses as a matrix for bilirubin removal.

PubMed

Xue, Maoqiang; Ling, Yisheng; Wu, Guisen; Liu, Xin; Ge, Dongtao; Shi, Wei

2013-01-01

Microporous anodic aluminum oxide (AAO) membranes were modified by 3-glycidoxypropyltrimethoxysilane to produce terminal epoxy groups. These were used to covalently link hydroxyethyl celluloses (HEC) to amplify reactive groups of AAO membrane. The hydroxyl groups of HEC-AAO composite membrane were further modified with 1,4-butanediol diglycidyl ether to link arginine as an affinity ligand. The contents of HEC and arginine of arginine-immobilized HEC-AAO membrane were 52.1 and 19.7mg/g membrane, respectively. As biomedical adsorbents, the arginine-immobilized HEC-AAO membranes were tested for bilirubin removal. The non-specific bilirubin adsorption on the unmodified HEC-AAO composite membranes was 0.8mg/g membrane. Higher bilirubin adsorption values, up to 52.6mg/g membrane, were obtained with the arginine-immobilized HEC-AAO membranes. Elution of bilirubin showed desorption ratio was up to 85% using 0.3M NaSCN solution as the desorption agent. Comparisons equilibrium and dynamic capacities showed that dynamic capacities were lower than the equilibrium capacities. In addition, the adsorption mechanism of bilirubin and the effects of temperature, initial concentration of bilirubin, albumin concentration and ionic strength on adsorption were also investigated. Copyright © 2012 Elsevier B.V. All rights reserved.

Hydrological and hydraulic models for determination of flood-prone and flood inundation areas

NASA Astrophysics Data System (ADS)

Aksoy, Hafzullah; Sadan Ozgur Kirca, Veysel; Burgan, Halil Ibrahim; Kellecioglu, Dorukhan

2016-05-01

Geographic Information Systems (GIS) are widely used in most studies on water resources. Especially, when the topography and geomorphology of study area are considered, GIS can ease the work load. Detailed data should be used in this kind of studies. Because of, either the complication of the models or the requirement of highly detailed data, model outputs can be obtained fast only with a good optimization. The aim in this study, firstly, is to determine flood-prone areas in a watershed by using a hydrological model considering two wetness indexes; the topographical wetness index, and the SAGA (System for Automated Geoscientific Analyses) wetness index. The wetness indexes were obtained in the Quantum GIS (QGIS) software by using the Digital Elevation Model of the study area. Flood-prone areas are determined by considering the wetness index maps of the watershed. As the second stage of this study, a hydraulic model, HEC-RAS, was executed to determine flood inundation areas under different return period-flood events. River network cross-sections required for this study were derived from highly detailed digital elevation models by QGIS. Also river hydraulic parameters were used in the hydraulic model. Modelling technology used in this study is made of freely available open source softwares. Based on case studies performed on watersheds in Turkey, it is concluded that results of such studies can be used for taking precaution measures against life and monetary losses due to floods in urban areas particularly.

Hydrology and Flood Profiles of Duck Creek and Jordan Creek Downstream from Egan Drive, Juneau, Alaska

USGS Publications Warehouse

Curran, Janet H.

2007-01-01

Hydrologic and hydraulic updates for Duck Creek and the lower part of Jordan Creek in Juneau, Alaska, included computation of new estimates of peak streamflow magnitudes and new water-surface profiles for the 10-, 50-, 100-, and 500-year floods. Computations for the 2-, 5-, 10-, 25-, 50-, 100-, 200-, and 500-year recurrence interval flood magnitudes for both streams used data from U.S. Geological Survey stream-gaging stations weighted with regional regression equations for southeast Alaska. The study area for the hydraulic model consisted of three channels: Duck Creek from Taku Boulevard near the stream's headwaters to Radcliffe Road near the end of the Juneau International Airport runway, an unnamed tributary to Duck Creek from Valley Boulevard to its confluence with Duck Creek, and Jordan Creek from a pedestrian bridge upstream from Egan Drive to Crest Street at Juneau International Airport. Field surveys throughout the study area provided channel geometry for 206 cross sections, and geometric and hydraulic characteristics for 29 culverts and 15 roadway, driveway, or pedestrian bridges. Hydraulic modeling consisted of application of the U.S. Army Corps of Engineers' Hydrologic Engineering Center River Analysis System (HEC-RAS) for steady-state flow at the selected recurrence intervals using an assumed high tide of 20 feet and roughness coefficients refined by calibration to measured water-surface elevations from a 2- to 5-year flood that occurred on November 21, 2005. Model simulation results identify inter-basin flow from Jordan Creek to the southeast at Egan Drive and from Duck Creek to Jordan Creek downstream from Egan Drive at selected recurrence intervals.

Decentralized State Estimation and Remedial Control Action for Minimum Wind Curtailment Using Distributed Computing Platform

DOE PAGES

Liu, Ren; Srivastava, Anurag K.; Bakken, David E.; ...

2017-08-17

Intermittency of wind energy poses a great challenge for power system operation and control. Wind curtailment might be necessary at the certain operating condition to keep the line flow within the limit. Remedial Action Scheme (RAS) offers quick control action mechanism to keep reliability and security of the power system operation with high wind energy integration. In this paper, a new RAS is developed to maximize the wind energy integration without compromising the security and reliability of the power system based on specific utility requirements. A new Distributed Linear State Estimation (DLSE) is also developed to provide the fast andmore » accurate input data for the proposed RAS. A distributed computational architecture is designed to guarantee the robustness of the cyber system to support RAS and DLSE implementation. The proposed RAS and DLSE is validated using the modified IEEE-118 Bus system. Simulation results demonstrate the satisfactory performance of the DLSE and the effectiveness of RAS. Real-time cyber-physical testbed has been utilized to validate the cyber-resiliency of the developed RAS against computational node failure.« less

Decentralized State Estimation and Remedial Control Action for Minimum Wind Curtailment Using Distributed Computing Platform

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

Liu, Ren; Srivastava, Anurag K.; Bakken, David E.

Intermittency of wind energy poses a great challenge for power system operation and control. Wind curtailment might be necessary at the certain operating condition to keep the line flow within the limit. Remedial Action Scheme (RAS) offers quick control action mechanism to keep reliability and security of the power system operation with high wind energy integration. In this paper, a new RAS is developed to maximize the wind energy integration without compromising the security and reliability of the power system based on specific utility requirements. A new Distributed Linear State Estimation (DLSE) is also developed to provide the fast andmore » accurate input data for the proposed RAS. A distributed computational architecture is designed to guarantee the robustness of the cyber system to support RAS and DLSE implementation. The proposed RAS and DLSE is validated using the modified IEEE-118 Bus system. Simulation results demonstrate the satisfactory performance of the DLSE and the effectiveness of RAS. Real-time cyber-physical testbed has been utilized to validate the cyber-resiliency of the developed RAS against computational node failure.« less

S-protected thiolated hydroxyethyl cellulose (HEC): Novel mucoadhesive excipient with improved stability.

PubMed

Leonaviciute, Gintare; Bonengel, Sonja; Mahmood, Arshad; Ahmad Idrees, Muneeb; Bernkop-Schnürch, Andreas

2016-06-25

The aim of this study was the design of novel S-protected thiolated hydroxyethyl cellulose (HEC) and the assessment of its mucoadhesive properties and biodegradability compared to the corresponding unmodified polymer. Thiolated HEC was S-protected via disulfide bond formation between 6-mercaptonicotinamide (6-MNA) and the thiol substructures of the polymer. In vitro screening of mucoadhesive properties was accomplished using two different methods: rotating cylinder studies and viscosity measurements. Moreover, biodegradability of these polymers by cellulase, xylanase and lysozyme was evaluated. MTT and LDH assays were performed on Caco-2 cells to determine the cytotoxicity of S-protected thiolated HEC. Thiolated HEC displayed 280.09±1.70μmol of free thiol groups per gram polymer. S-protected thiolated HEC exhibiting 270.8±21.11μmol immobilized 6-MNA ligands per gram of polymer was shown being 2.4-fold more mucoadhesive compared to thiolated HEC. No mucoadhesion was observed in case of unmodified HEC. Results were in a good agreement with rheological studies. The presence of free thiol moieties likely caused lower degree of hydrolysis by xylanase, whereas the degradation by both enzymes cellulase and xylanase was more hampered when 6-MNA was introduced as ligand for thiol group's protection. Findings in cell viability revealed that all three conjugates were non-toxic. S-protection of thiolated hydroxyethyl cellulose improved mucoadhesive properties and provided pronounced stability towards enzymatic attack, that makes this excipient superior for non-invasive drug administration over thiolated and unmodified forms. Copyright © 2016 Elsevier Ltd. All rights reserved.

The RAS mutation status predicts survival in patients undergoing hepatic resection for colorectal liver metastases: The results from a genetic analysis of all-RAS.

PubMed

Amikura, Katsumi; Akagi, Kiwamu; Ogura, Toshiro; Takahashi, Amane; Sakamoto, Hirohiko

2018-03-01

We investigated the impact of mutations in KRAS exons 3-4 and NRAS exons 2-3 in addition to KRAS exon 2, so-called all-RAS mutations, in patients with colorectal liver metastasis (CLM) undergoing hepatic resection. We analyzed 421 samples from CLM patients for their all-RAS mutation status to compare the overall survival rate (OS), recurrence-free survival rate (RFS), and the pattern of recurrence between the patients with and without RAS mutations. RAS mutations were detected in 191 (43.8%). Thirty-two rare mutations (12.2%) were detected in 262 patients with KRAS exon 2 wild-type. After excluding 79 patients who received anti-EGFR antibody therapy, 168 were classified as all-RAS wild-type, and 174 as RAS mutant-type. A multivariate analysis of factors associated with OS and RFS identified the RAS status as an independent factor (OS; hazard ratio [HR] = 1.672, P = 0.0031, RFS; HR = 1.703, P = 0.0024). Recurrence with lung metastasis was observed significantly more frequent in patients with RAS mutations than in patients with RAS wild-type (P = 0.0005). Approximately half of CLM patients may have a RAS mutation. CLM patients with RAS mutations had a significantly worse survival rate in comparison to patients with RAS wild-type, regardless of the administration of anti-EGFR antibody therapy. © 2017 Wiley Periodicals, Inc.

Dynamic remedial action scheme using online transient stability analysis

NASA Astrophysics Data System (ADS)

Shrestha, Arun

Economic pressure and environmental factors have forced the modern power systems to operate closer to their stability limits. However, maintaining transient stability is a fundamental requirement for the operation of interconnected power systems. In North America, power systems are planned and operated to withstand the loss of any single or multiple elements without violating North American Electric Reliability Corporation (NERC) system performance criteria. For a contingency resulting in the loss of multiple elements (Category C), emergency transient stability controls may be necessary to stabilize the power system. Emergency control is designed to sense abnormal conditions and subsequently take pre-determined remedial actions to prevent instability. Commonly known as either Remedial Action Schemes (RAS) or as Special/System Protection Schemes (SPS), these emergency control approaches have been extensively adopted by utilities. RAS are designed to address specific problems, e.g. to increase power transfer, to provide reactive support, to address generator instability, to limit thermal overloads, etc. Possible remedial actions include generator tripping, load shedding, capacitor and reactor switching, static VAR control, etc. Among various RAS types, generation shedding is the most effective and widely used emergency control means for maintaining system stability. In this dissertation, an optimal power flow (OPF)-based generation-shedding RAS is proposed. This scheme uses online transient stability calculation and generator cost function to determine appropriate remedial actions. For transient stability calculation, SIngle Machine Equivalent (SIME) technique is used, which reduces the multimachine power system model to a One-Machine Infinite Bus (OMIB) equivalent and identifies critical machines. Unlike conventional RAS, which are designed using offline simulations, online stability calculations make the proposed RAS dynamic and adapting to any power system configuration and operating state. The generation-shedding cost is calculated using pre-RAS and post-RAS OPF costs. The criteria for selecting generators to trip is based on the minimum cost rather than minimum amount of generation to shed. For an unstable Category C contingency, the RAS control action that results in stable system with minimum generation shedding cost is selected among possible candidate solutions. The RAS control actions update whenever there is a change in operating condition, system configuration, or cost functions. The effectiveness of the proposed technique is demonstrated by simulations on the IEEE 9-bus system, the IEEE 39-bus system, and IEEE 145-bus system. This dissertation also proposes an improved, yet relatively simple, technique for solving Transient Stability-Constrained Optimal Power Flow (TSC-OPF) problem. Using the SIME method, the sets of dynamic and transient stability constraints are reduced to a single stability constraint, decreasing the overall size of the optimization problem. The transient stability constraint is formulated using the critical machines' power at the initial time step, rather than using the machine rotor angles. This avoids the addition of machine steady state stator algebraic equations in the conventional OPF algorithm. A systematic approach to reach an optimal solution is developed by exploring the quasi-linear behavior of critical machine power and stability margin. The proposed method shifts critical machines active power based on generator costs using an OPF algorithm. Moreover, the transient stability limit is based on stability margin, and not on a heuristically set limit on OMIB rotor angle. As a result, the proposed TSC-OPF solution is more economical and transparent. The proposed technique enables the use of fast and robust commercial OPF tool and time-domain simulation software for solving large scale TSC-OPF problem, which makes the proposed method also suitable for real-time application.

The Social Effects of the Australian Higher Education Contribution Scheme (HECS)

ERIC Educational Resources Information Center

Marks, Gary Neil

2009-01-01

Australia's Higher Education Contribution Scheme (HECS) is an income contingent loan scheme, in which university students pay back part of the costs of their tuition after their post-university income reaches a certain threshold, is an important policy innovation for the financing of higher education. However, its critics claim that HECS increases…

Arabidopsis HECATE genes function in phytohormone control during gynoecium development.

PubMed

Schuster, Christoph; Gaillochet, Christophe; Lohmann, Jan U

2015-10-01

The fruit, which develops from the fertilised gynoecium formed in the innermost whorl of the flower, is the reproductive organ and one of the most complex structures of an angiosperm plant. Phytohormones play important roles during flower and fruit patterning, morphogenesis and growth, and there is emerging evidence for a cross-talk between different classes of plant hormones throughout these processes. Here, we show that the bHLH transcription factors HECATE 1 (HEC1), HEC2 and HEC3, which have previously been identified as essential components of transmitting tract formation, affect both auxin and cytokinin responses during reproductive tissue development. We find that HEC1 interacts with SPATULA (SPT) to control carpel fusion and that both transcription factors restrict sensitivity to cytokinin in the gynoecium. In addition, HEC1 is tightly integrated into the auxin-signalling network at the levels of biosynthesis, transport and transcriptional response. Based on this data, we propose that HEC1 acts as a local modulator of auxin and cytokinin responses to control gynoecium development in Arabidopsis. © 2015. Published by The Company of Biologists Ltd.

Rat embryo cells immortalized with transfected oncogenes are transformed by gamma irradiation.

PubMed

Endlich, B; Salavati, R; Sullivan, T; Ling, C C

1992-12-01

Cesium-137 gamma rays were used to transform rat embryo cells (REC) which were first transfected with activated c-myc or c-Ha-ras oncogenes to produce immortal cell lines (REC:myc and REC:ras). When exposed to 6 Gy of 137Cs gamma rays, some cells became morphologically transformed with focus formation frequencies of approximately 3 x 10(-4) for REC:myc and approximately 1 x 10(-4) for REC:ras, respectively. Cells isolated from foci of gamma-ray-transformed REC:myc (REC:myc:gamma) formed anchorage-independent colonies and were tumorigenic in nude mice, but foci from gamma-ray-transformed REC:ras (REC:ras:gamma) did not exhibit either of these criteria of transformation. Similar to the results with gamma irradiation, we observed a sequence-dependent phenomenon when myc and ras were transfected into REC, one at a time. REC immortalized by ras transfection were not converted to a tumorigenic phenotype by secondary transfection with myc, but REC transfected with myc were very susceptible to transformation by subsequent ras transfection. This suggests that myc-immortalized cells are more permissive to transformation via secondary treatments. In sequentially transfected REC, myc expression was high whether it was transfected first or second, whereas ras expression was highest when the ras gene was transfected secondarily into myc-containing REC. Molecular analysis of REC:ras:gamma transformants showed no alterations in structure of the transfected ras or of the endogenous ras, myc, p53, or fos genes. The expression of ras and p53 was increased in some isolates of REC:ras:gamma, but myc and fos expression were not affected. Similarly, REC:myc:gamma transformants did not demonstrate rearrangement or amplification of the transfected or the endogenous myc genes, or of the potentially cooperating Ha-, Ki-, or N-ras genes. Northern hybridization analysis revealed increased expression of N-ras in two isolates, REC:myc:gamma 33 and gamma 41, but no alterations in the expression of myc, raf, Ha-ras, or Ki-ras genes in any REC:myc transformant. DNA from several transformed REC:myc:gamma cell lines induced focus formation in recipient C3H 10T1/2 and NIH 3T3 cells. The NIH 3T3 foci tested positive when hybridized to a probe for rat repetitive DNA. A detailed analysis of the NIH 3T3 transformants generated from REC:myc:gamma 33 and gamma 41 DNA failed to detect Ha-ras, Ki-ras, raf, neu, trk, abl, fms, or src oncogenes of rat origin.(ABSTRACT TRUNCATED AT 400 WORDS)

Advanced airway management in hoist and longline operations in mountain HEMS - considerations in austere environments: a narrative review This review is endorsed by the International Commission for Mountain Emergency Medicine (ICAR MEDCOM).

PubMed

Pietsch, Urs; Knapp, Jürgen; Kreuzer, Oliver; Ney, Ludwig; Strapazzon, Giacomo; Lischke, Volker; Albrecht, Roland; Phillips, Patrick; Rauch, Simon

2018-04-03

Providing sufficient oxygenation and ventilation is of paramount importance for the survival of emergency patients. Therefore, advanced airway management is one of the core tasks for every rescue team. Endotracheal intubation is the gold standard to secure the airway in the prehospital setting. This review aims to highlight special considerations for advanced airway management preceding human external cargo (HEC) evacuations. We systematically searched MEDLINE, EMBASE, and PubMed in August 2017 for articles on airway management and ventilation in patients before hoist or longline operation in HEMS. Relevant reference lists were hand-searched. Three articles with regard to advanced airway management and five articles concerning the epidemiology of advanced airway management in hoist or longline rescue missions were included. We found one case report regarding ventilation during hoist operations. The exact incidence of advanced airway management before evacuation of a patient by HEC is unknown but seems to be very low (< 5%). There are several hazards which can impede mechanical ventilation of patients during HEC extractions: loss of equipment, hyperventilation, inability to ventilate and consequent hypoxia, as well as inadequacy of monitoring. Advanced airway management prior to HEC operation is rarely performed. If intubation before helicopter hoist operations (HHO) and human cargo sling (HCS) extraction is considered by the rescue team, a risk/benefit analysis should be performed and a clear standard operating procedure (SOP) should be defined. Continuous and rigorous training including the whole crew is required. An international registry on airway management during HEC extraction would be desirable.

Efficacy and safety of rolapitant for prevention of chemotherapy-induced nausea and vomiting over multiple cycles of moderately or highly emetogenic chemotherapy.

PubMed

Rapoport, Bernardo; Schwartzberg, Lee; Chasen, Martin; Powers, Dan; Arora, Sujata; Navari, Rudolph; Schnadig, Ian

2016-04-01

Rolapitant, a novel neurokinin-1 receptor antagonist (RA), was shown to protect against delayed chemotherapy-induced nausea and vomiting (CINV) during the first cycle of moderately emetogenic chemotherapy (MEC) or highly emetogenic chemotherapy (HEC) in randomized, double-blind trials. This analysis explored the efficacy and safety of rolapitant in preventing CINV over multiple cycles of MEC or HEC. Patients in one phase III MEC, one phase II HEC, and two phase III HEC clinical trials were randomized to receive oral rolapitant (180 mg) or placebo in combination with a 5-hydroxytryptamine type 3 RA and dexamethasone. Regardless of response in cycle 1, patients could continue the same antiemetic treatment for up to six cycles. On days 6-8 of each subsequent chemotherapy cycle, patients reported the incidence of emesis and/or nausea interfering with normal daily life. Post hoc analyses of pooled safety and efficacy data from the four trials were performed for cycles 2-6. Significantly more patients receiving rolapitant than control reported no emesis or interfering nausea (combined measure) in cycles 2 (p = 0.006), 3 (p < 0.001), 4 (p = 0.001), and 5 (p = 0.021). Over cycles 1-6, time-to-first emesis was significantly longer with rolapitant than with control (p < 0.001). The incidence of treatment-related adverse events during cycles 2-6 was similar in rolapitant (5.5%) and control (6.8%) arms. No cumulative toxicity was observed. Over multiple cycles of MEC or HEC, rolapitant provided superior CINV protection and reduced emesis and nausea interfering with daily life compared with control and remained well tolerated. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

New insights into RAS biology reinvigorate interest in mathematical modeling of RAS signaling

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

Erickson, Keesha E.; Rukhlenko, Oleksii S.; Posner, Richard G.

RAS is the most frequently mutated gene across human cancers, but developing inhibitors of mutant RAS has proven to be challenging. Given the difficulties of targeting RAS directly, drugs that impact the other components of pathways where mutant RAS operates may potentially be effective. However, the system-level features, including different localizations of RAS isoforms, competition between downstream effectors, and interlocking feedback and feed-forward loops, must be understood to fully grasp the opportunities and limitations of inhibiting specific targets. Mathematical modeling can help us discern the system-level impacts of these features in normal and cancer cells. New technologies enable the acquisitionmore » of experimental data that will facilitate development of realistic models of oncogenic RAS behavior. In light of the wealth of empirical data accumulated over decades of study and the advancement of experimental methods for gathering new data, modelers now have the opportunity to advance progress toward realization of targeted treatment for mutant RAS-driven cancers.« less

New insights into RAS biology reinvigorate interest in mathematical modeling of RAS signaling

DOE PAGES

Erickson, Keesha E.; Rukhlenko, Oleksii S.; Posner, Richard G.; ...

2018-03-05

RAS is the most frequently mutated gene across human cancers, but developing inhibitors of mutant RAS has proven to be challenging. Given the difficulties of targeting RAS directly, drugs that impact the other components of pathways where mutant RAS operates may potentially be effective. However, the system-level features, including different localizations of RAS isoforms, competition between downstream effectors, and interlocking feedback and feed-forward loops, must be understood to fully grasp the opportunities and limitations of inhibiting specific targets. Mathematical modeling can help us discern the system-level impacts of these features in normal and cancer cells. New technologies enable the acquisitionmore » of experimental data that will facilitate development of realistic models of oncogenic RAS behavior. In light of the wealth of empirical data accumulated over decades of study and the advancement of experimental methods for gathering new data, modelers now have the opportunity to advance progress toward realization of targeted treatment for mutant RAS-driven cancers.« less

New insights into RAS biology reinvigorate interest in mathematical modeling of RAS signaling.

PubMed

Erickson, Keesha E; Rukhlenko, Oleksii S; Posner, Richard G; Hlavacek, William S; Kholodenko, Boris N

2018-03-05

RAS is the most frequently mutated gene across human cancers, but developing inhibitors of mutant RAS has proven to be challenging. Given the difficulties of targeting RAS directly, drugs that impact the other components of pathways where mutant RAS operates may potentially be effective. However, the system-level features, including different localizations of RAS isoforms, competition between downstream effectors, and interlocking feedback and feed-forward loops, must be understood to fully grasp the opportunities and limitations of inhibiting specific targets. Mathematical modeling can help us discern the system-level impacts of these features in normal and cancer cells. New technologies enable the acquisition of experimental data that will facilitate development of realistic models of oncogenic RAS behavior. In light of the wealth of empirical data accumulated over decades of study and the advancement of experimental methods for gathering new data, modelers now have the opportunity to advance progress toward realization of targeted treatment for mutant RAS-driven cancers. Copyright © 2018 Elsevier Ltd. All rights reserved.

Cognitive performance, symptoms and counter-regulation during hypoglycaemia in patients with type 1 diabetes and high or low renin-angiotensin system activity.

PubMed

Høi-Hansen, Thomas; Pedersen-Bjergaard, Ulrik; Andersen, Rikke Due; Kristensen, Peter Lommer; Thomsen, Carsten; Kjaer, Troels; Høgenhaven, Hans; Smed, Annelise; Holst, Jens Juul; Dela, Flemming; Boomsma, Frans; Thorsteinsson, Birger

2009-12-01

High basal renin-angiotensin system (RAS) activity is associated with increased risk of severe hypoglycaemia in type 1 diabetes. We tested whether this might be explained by more pronounced cognitive dysfunction during hypoglycaemia in patients with high RAS activity than in patients with low RAS activity. Nine patients with type 1 diabetes and high and nine with low RAS activity were subjected to hypoglycaemia and euglycaemia in a cross-over study using an intravenous insulin infusion protocol. Cognitive function, electroencephalography, auditory evoked potentials and hypoglycaemic symptoms were recorded. At a hypoglycaemic nadir of 2.2 (SD 0.3) mmol/L the high RAS group displayed significant deterioration in cognitive performance during hypoglycaemia in the three most complex reaction time tasks. In the low RAS group, hypoglycaemia led to cognitive dysfunction in only one reaction time task. The high RAS group reported lower symptom scores during hypoglycaemia than the low RAS group, suggesting poorer hypoglycaemia awareness. High RAS activity is associated with increased cognitive dysfunction and blunted symptoms during mild hypoglycaemia compared to low RAS activity. This may explain why high RAS activity is a risk factor for severe hypoglycaemia in type 1 diabetes.

Incoherent feedforward control governs adaptation of activated ras in a eukaryotic chemotaxis pathway.

PubMed

Takeda, Kosuke; Shao, Danying; Adler, Micha; Charest, Pascale G; Loomis, William F; Levine, Herbert; Groisman, Alex; Rappel, Wouter-Jan; Firtel, Richard A

2012-01-03

Adaptation in signaling systems, during which the output returns to a fixed baseline after a change in the input, often involves negative feedback loops and plays a crucial role in eukaryotic chemotaxis. We determined the dynamical response to a uniform change in chemoattractant concentration of a eukaryotic chemotaxis pathway immediately downstream from G protein-coupled receptors. The response of an activated Ras showed near-perfect adaptation, leading us to attempt to fit the results using mathematical models for the two possible simple network topologies that can provide perfect adaptation. Only the incoherent feedforward network accurately described the experimental results. This analysis revealed that adaptation in this Ras pathway is achieved through the proportional activation of upstream components and not through negative feedback loops. Furthermore, these results are consistent with a local excitation, global inhibition mechanism for gradient sensing, possibly with a Ras guanosine triphosphatase-activating protein acting as a global inhibitor.

Mapping the functional versatility and fragility of Ras GTPase signaling circuits through in vitro network reconstitution

PubMed Central

Coyle, Scott M; Lim, Wendell A

2016-01-01

The Ras-superfamily GTPases are central controllers of cell proliferation and morphology. Ras signaling is mediated by a system of interacting molecules: upstream enzymes (GEF/GAP) regulate Ras’s ability to recruit multiple competing downstream effectors. We developed a multiplexed, multi-turnover assay for measuring the dynamic signaling behavior of in vitro reconstituted H-Ras signaling systems. By including both upstream regulators and downstream effectors, we can systematically map how different network configurations shape the dynamic system response. The concentration and identity of both upstream and downstream signaling components strongly impacted the timing, duration, shape, and amplitude of effector outputs. The distorted output of oncogenic alleles of Ras was highly dependent on the balance of positive (GAP) and negative (GEF) regulators in the system. We found that different effectors interpreted the same inputs with distinct output dynamics, enabling a Ras system to encode multiple unique temporal outputs in response to a single input. We also found that different Ras-to-GEF positive feedback mechanisms could reshape output dynamics in distinct ways, such as signal amplification or overshoot minimization. Mapping of the space of output behaviors accessible to Ras provides a design manual for programming Ras circuits, and reveals how these systems are readily adapted to produce an array of dynamic signaling behaviors. Nonetheless, this versatility comes with a trade-off of fragility, as there exist numerous paths to altered signaling behaviors that could cause disease. DOI: http://dx.doi.org/10.7554/eLife.12435.001 PMID:26765565

Hospital/clinical ethics committees' notion: an overview

PubMed Central

Hajibabaee, Fatemeh; Joolaee, Soodabeh; Cheraghi, Mohammad Ali; Salari, Pooneh; Rodney, Patricia

2016-01-01

Hospital ethics committees (HECs) help clinicians deal with the ethical challenges which have been raised during clinical practice. A comprehensive literature review was conducted to provide a historical background of the development of HECs internationally and describe their functions and practical challenges of their day to day work. This is the first part of a comprehensive literature review conducted between February 2014 and August 2016 by searching through scientific databases. The keyword ethics committee, combined with hospital, clinic, and institution, was used without a time limitation. All original and discussion articles, as well as other scientific documents were included. Of all the articles and theses found using these keywords, only 56 were consistent with the objectives of the study. Based on the review goals, the findings were divided into three main categories; the inception of HECs in the world, the function of HECs, and the challenges of HECs. According to the results, the Americas Region and European Region countries have been the most prominent considering the establishment of HECs. However, the majority of the Eastern Mediterranean Region and South-East Asia Region countries are only beginning to establish these committees in their hospitals. The results highlight the status and functions of HECs in different countries and may be used as a guide by health policymakers and managers who are at the inception of establishing these committees in their hospitals. PMID:28523118

Quantitative two-dimensional gel electrophoresis analysis of human fibroblasts transformed by ras oncogenes.

PubMed

Miller, M J; Maher, V M; McCormick, J J

1992-11-01

Quantitative two-dimensional gel electrophoresis was used to compare the cellular protein patterns of a normal foreskin-derived human fibroblasts cell line (LG1) and three immortal derivatives of LG1. One derivative, designated MSU-1.1 VO, was selected for its ability to grow in the absence of serum and is non-tumorigenic in athymic mice. The other two strains were selected for focus-formation following transfection with either Ha-ras or N-ras oncogenes and form high grade malignant tumors. Correspondence and cluster analysis provided a nonbiased estimate of the relative similarity of the different two-dimensional patterns. These techniques separated the gel patterns into three distinct classes: LG1, MSU-1.1 VO, and the ras transformed cell strains. The MSU-1.1 VO cells were more closely related to the parental LG1 than to the ras-transformed cells. The differences between the three classes were primarily quantitative in nature: 16% of the spots demonstrated statistically significant changes (P < 0.01, T test, mean ratio of intensity > 2) in the rate of incorporation of radioactive amino acids. The patterns from the two ras-transformed cell strains were similar, and variations in the expression of proteins that occurred between the separate experiments obscured consistent differences between the Ha-ras and N-ras transformed cells. However, while only 9 out of 758 spots were classified as different (1%), correspondence analysis could consistently separate the two ras transformants. One of these spots was five times more intense in the Ha-ras transformed cells than the N-ras.(ABSTRACT TRUNCATED AT 250 WORDS)

Deconstruction of the Ras switching cycle through saturation mutagenesis

PubMed Central

Bandaru, Pradeep; Shah, Neel H; Bhattacharyya, Moitrayee; Barton, John P; Kondo, Yasushi; Cofsky, Joshua C; Gee, Christine L; Chakraborty, Arup K; Kortemme, Tanja; Ranganathan, Rama; Kuriyan, John

2017-01-01

Ras proteins are highly conserved signaling molecules that exhibit regulated, nucleotide-dependent switching between active and inactive states. The high conservation of Ras requires mechanistic explanation, especially given the general mutational tolerance of proteins. Here, we use deep mutational scanning, biochemical analysis and molecular simulations to understand constraints on Ras sequence. Ras exhibits global sensitivity to mutation when regulated by a GTPase activating protein and a nucleotide exchange factor. Removing the regulators shifts the distribution of mutational effects to be largely neutral, and reveals hotspots of activating mutations in residues that restrain Ras dynamics and promote the inactive state. Evolutionary analysis, combined with structural and mutational data, argue that Ras has co-evolved with its regulators in the vertebrate lineage. Overall, our results show that sequence conservation in Ras depends strongly on the biochemical network in which it operates, providing a framework for understanding the origin of global selection pressures on proteins. DOI: http://dx.doi.org/10.7554/eLife.27810.001 PMID:28686159

Home-Made Money: Consumer's Guide to Home Equity Conversion.

ERIC Educational Resources Information Center

Scholen, Ken

This guide was written to introduce consumers to home equity conversion (HEC) plans that are currently available and to explain the current state of HEC developments. It describes how the basic types of HEC plans work, gives examples of how how they can be used, discusses their advantages and disadvantages, and tells where they are available.…

The intracellular angiotensin system buffers deleterious effects of the extracellular paracrine system

PubMed Central

Villar-Cheda, Begoña; Costa-Besada, Maria A; Valenzuela, Rita; Perez-Costas, Emma; Melendez-Ferro, Miguel; Labandeira-Garcia, Jose L

2017-01-01

The ‘classical’ renin–angiotensin system (RAS) is a circulating system that controls blood pressure. Local/paracrine RAS, identified in a variety of tissues, including the brain, is involved in different functions and diseases, and RAS blockers are commonly used in clinical practice. A third type of RAS (intracellular/intracrine RAS) has been observed in some types of cells, including neurons. However, its role is still unknown. The present results indicate that in brain cells the intracellular RAS counteracts the intracellular superoxide/H2O2 and oxidative stress induced by the extracellular/paracrine angiotensin II acting on plasma membrane receptors. Activation of nuclear receptors by intracellular or internalized angiotensin triggers a number of mechanisms that protect the cell, such as an increase in the levels of protective angiotensin type 2 receptors, intracellular angiotensin, PGC-1α and IGF-1/SIRT1. Interestingly, this protective mechanism is altered in isolated nuclei from brains of aged animals. The present results indicate that at least in the brain, AT1 receptor blockers acting only on the extracellular or paracrine RAS may offer better protection of cells. PMID:28880266

H-Ras and K-Ras Oncoproteins Induce Different Tumor Spectra When Driven by the Same Regulatory Sequences.

PubMed

Drosten, Matthias; Simón-Carrasco, Lucía; Hernández-Porras, Isabel; Lechuga, Carmen G; Blasco, María T; Jacob, Harrys K C; Fabbiano, Salvatore; Potenza, Nicoletta; Bustelo, Xosé R; Guerra, Carmen; Barbacid, Mariano

2017-02-01

Genetic studies in mice have provided evidence that H-Ras and K-Ras proteins are bioequivalent. However, human tumors display marked differences in the association of RAS oncogenes with tumor type. Thus, to further assess the bioequivalence of oncogenic H-Ras and K-Ras, we replaced the coding region of the murine K-Ras locus with H-Ras G12V oncogene sequences. Germline expression of H-Ras G12V or K-Ras G12V from the K-Ras locus resulted in embryonic lethality. However, expression of these genes in adult mice led to different tumor phenotypes. Whereas H-Ras G12V elicited papillomas and hematopoietic tumors, K-Ras G12V induced lung tumors and gastric lesions. Pulmonary expression of H-Ras G12V created a senescence-like state caused by excessive MAPK signaling. Likewise, H-Ras G12V but not K-Ras G12V induced senescence in mouse embryonic fibroblasts. Label-free quantitative analysis revealed that minor differences in H-Ras G12V expression levels led to drastically different biological outputs, suggesting that subtle differences in MAPK signaling confer nonequivalent functions that influence tumor spectra induced by RAS oncoproteins. Cancer Res; 77(3); 707-18. ©2016 AACR. ©2016 American Association for Cancer Research.

Impact of Emergent Circulating Tumor DNA RAS Mutation in Panitumumab-Treated Chemoresistant Metastatic Colorectal Cancer.

PubMed

Kim, Tae Won; Peeters, Marc; Thomas, Anne L; Gibbs, Peter; Hool, Kristina; Zhang, Jianqi; Ang, Agnes; Bach, Bruce Allen; Price, Timothy

2018-06-13

The accumulation of emergent RAS mutations during anti-epidermal growth factor receptor (EGFR) therapy is of interest as a mechanism for acquired resistance to anti-EGFR treatment. Plasma analysis of circulating tumor (ct) DNA is a minimally invasive and highly sensitive method to determine RAS mutational status. This biomarker analysis of the global phase III ASPECCT study used next-generation sequencing to detect expanded RAS ctDNA mutations in panitumumab-treated patients. Plasma samples collected at baseline and posttreatment were analyzed categorically for the presence of RAS mutations by the Plasma Select -R™ 64-gene panel at 0.1% sensitivity. Among panitumumab-treated patients with evaluable plasma samples at baseline (n = 238), 188 (79%) were wild-type (WT) RAS, and 50 (21%) were mutant RAS Of the 188 patients with baseline ctDNA WT RAS status, 164 had evaluable posttreatment results with a 32% rate of emergent RAS mutations. The median overall survival (OS) for WT and RAS mutant status by ctDNA at baseline was 13.7 (95% confidence interval: 11.5-15.4) and 7.9 months (6.4-9.6), respectively ( P < 0.0001). Clinical outcomes were not significantly different between patients with and without emergent ctDNA RAS mutations. Although patients with baseline ctDNA RAS mutations had worse outcomes than patients who were WT RAS before initiating treatment, emergent ctDNA RAS mutations were not associated with less favorable patient outcomes in panitumumab-treated patients. Further research is needed to determine a clinically relevant threshold for baseline and emergent ctDNA RAS mutations. Copyright ©2018, American Association for Cancer Research.

Nurses' knowledge, attitudes and willingness to participate officially in workplace Healthcare Ethics Committees (HEC).

PubMed

Rubinstein, Dorit; Tabak, Nili

2012-03-01

This research was designed to assess nurses' perceptions, knowledge, attitudes and intentions in relation to nurse participation in Healthcare Ethics Committees (HECs). A convenience sample of 87 nurses from five Israeli hospitals completed a self-administered questionnaire, whose data were then analyzed by quantitative statistics. The main findings were that large percentages of nurses were totally ignorant of the existence and functioning of the HEC in their workplaces. Nurses in managerial roles were (a) much more knowledgeable on these matters than staff nurses and (b) regarded more positively the idea that nurses had an obligation to sit on such committees. Workplace role and rank in the organizational hierarchy had a stronger impact on nurse attitudes to HEC work than level of education. Overall, nurse willingness to sit on an HEC and to take special training in preparation for such a role were high.

Quantification of systemic renin-angiotensin system peptides of hypertensive black and white African men established from the RAS-Fingerprint®.

PubMed

van Rooyen, J M; Poglitsch, M; Huisman, H W; Mels, Cmc; Kruger, R; Malan, L; Botha, S; Lammertyn, L; Gafane, L; Schutte, A E

2016-10-01

The objective of this study was to make use of a quantitative and qualitative approach comparing the systemic renin-angiotensin system (RAS) of hypertensive black and white African men by using RAS equilibrium analysis. This sub-study involved 23 black (n = 15) and white (n = 8) hypertensive men aged 39.5-41 years, living in the North West Province of South Africa. The RAS-Fingerprinting was determined with LC-MS/MS quantification of angiotensin peptides. Blood pressure and other variables were determined with known methods. The main finding of this study was the significant lower Ang I (<5.0 and 45.1 pg/ml; p = 0.005) and Ang II (15.6 and 123.9 pg/ml; p ⩽ 0.001) encountered in the hypertensive black African men compared to their white counterparts. Levels of Ang 1-5 (downstream metabolite of Ang 1-7) (1.8 and 3.0 pg/ml), were detected in black and white hypertensive men, respectively. The observed differences between circulating RAS components, which are reflected via equilibrium angiotensin levels, point to a distinctive molecular regulation of the RAAS in the two study cohorts. The increased peripheral resistance observed in hypertensive black individuals might take over a dominant role in control of blood pressure in this study population. A novel highly sensitive LC-MS/MS method resolved the issue of peptide recovery variations during sample preparation by using internal standards for each individual angiotensin metabolite. © The Author(s) 2016.

A universal method for the mutational analysis of K-ras and p53 gene in non-small-cell lung cancer using formalin-fixed paraffin-embedded tissue.

PubMed

Sarkar, F H; Valdivieso, M; Borders, J; Yao, K L; Raval, M M; Madan, S K; Sreepathi, P; Shimoyama, R; Steiger, Z; Visscher, D W

1995-12-01

The p53 tumor suppressor gene has been found to be altered in almost all human solid tumors, whereas K-ras gene mutations have been observed in a limited number of human cancers (adenocarcinoma of colon, pancreas, and lung). Studies of mutational inactivation for both genes in the same patient's sample on non-small-cell lung cancer have been limited. In an effort to perform such an analysis, we developed and compared methods (for the mutational detection of p53 and K-ras gene) that represent a modified and universal protocol, in terms of DNA extraction, polymerase chain reaction (PCR) amplification, and nonradioisotopic PCR-single-strand conformation polymorphism (PCR-SSCP) analysis, which is readily applicable to either formalin-fixed, paraffin-embedded tissues or frozen tumor specimens. We applied this method to the evaluation of p53 (exons 5-8) and K-ras (codon 12 and 13) gene mutations in 55 cases of non-small-cell lung cancer. The mutational status in the p53 gene was evaluated by radioisotopic PCR-SSCP and compared with PCR-SSCP utilizing our standardized nonradioisotopic detection system using a single 6-microns tissue section. The mutational patterns observed by PCR-SSCP were subsequently confirmed by PCR-DNA sequencing. The mutational status in the K-ras gene was similarly evaluated by PCR-SSCP, and the specific mutation was confirmed by Southern slot-blot hybridization using 32P-labeled sequence-specific oligonucleotide probes for codons 12 and 13. Mutational changes in K-ras (codon 12) were found in 10 of 55 (18%) of non-small-cell lung cancers. Whereas adenocarcinoma showed K-ras mutation in 33% of the cases at codon 12, only one mutation was found at codon 13. As expected, squamous cell carcinoma samples (25 cases) did not show K-ras mutations. Mutations at exons 5-8 of the p53 gene were documented in 19 of 55 (34.5%) cases. Ten of the 19 mutations were single nucleotide point mutations, leading to amino acid substitution. Six showed insertional mutation, and three showed deletion mutations. Only three samples showed mutations of both K-ras and p53 genes. We conclude that although K-ras and p53 gene mutations are frequent in non-small-cell lung cancer, mutations of both genes in the same patient's samples are not common. We also conclude that this universal nonradioisotopic method is superior to other similar methods and is readily applicable to the rapid screening of large numbers of formalin-fixed, paraffin-embedded or frozen samples for the mutational analysis of multiple genes.

Flash flood hazard assessment through modelling in small semi-arid watersheds. The example of the Beni Mellal watershed in Morocco

NASA Astrophysics Data System (ADS)

Werren, G.; Balin, D.; Reynard, E.; Lane, S. N.

2012-04-01

Flood modelling is essential for flood hazard assessment. Modelling becomes a challenge in small, ungauged watersheds prone to flash floods, like the ones draining the town of Beni Mellal (Morocco). Four temporary streams meet in the urban area of Beni Mellal, producing every year sheet floods, harmful to infrastructure and to people. Here, statistical analysis may not give realistic results, but the study of these repeated real flash flood events may provide a better understanding of watershed specific hydrology. This study integrates a larger cooperation project between Switzerland and Morroco, aimed at knowledge transfer in disaster risk reduction, especially through hazard mapping and land-use planning, related to implementation of hazard maps. Hydrologic and hydraulic modelling was carried out to obtain hazard maps. An important point was to find open source data and methods that could still produce a realistic model for the area concerned, in order to provide easy-to-use, cost-effective tools for risk management in developing countries like Morocco, where routine data collection is largely lacking. The data used for modelling is the Web available TRMM 3-Hour 0.25 degree rainfall data provided by the Tropical Rainfall Measurement Mission Project (TRMM). Hydrologic modelling for discharge estimation was undertaken using methods available in the HEC-HMS software provided by the US Army Corps of Engineers® (USACE). Several transfer models were used, so as to choose the best-suited method available. As no model calibration was possible for no measured flow data was available, a one-at-the-time sensitivity analysis was performed on the parameters chosen, in order to detect their influence on the results. But the most important verification method remained field observation, through post-flood field campaigns aimed at mapping water surfaces and depths in the flooded areas, as well as river section monitoring, where rough discharge estimates could be obtained using empirical equations. Another information source was local knowledge, as people could give a rough estimation of concentration time by describing flood evolution. Finally, hydraulic modelling of the flooded areas in the urban perimeter was performed using the USACE HEC-RAS® software capabilities. A specific challenge at this stage was field morphology, as the flooded areas form large alluvial fans, with very different flood behaviour compared to flood plains. Model "calibration" at this stage was undertaken using the mapped water surfaces and depths. Great care was taken for field geometry design, where field observations, measured cross sections and field images were used to improve the existing DTM data. The model included protection dikes already built by local authorities in their flood-fight effort. Because of flash-flood specific behaviour, only maximal flooded surfaces and flow velocities were simulated through steady flow analysis in HEC-RAS. The discharge estimates obtained for the chosen event were comparable to 10-year return periods as estimated by the watershed authorities. Times of concentration correspond to this previous estimation and to local people descriptions. The modelled water surfaces reflect field reality. Flash-flood modelling demands extensive knowledge of the studied field in order to compensate data scarcity. However, more precise data, like radar rainfall estimates available in Morocco, would definitely improve outputs. In this perspective, better data access at the local level and good use of the available methods could benefit the disaster risk reduction effort as a whole.

Design of bridge deck drainage : HEC 21

DOT National Transportation Integrated Search

1993-05-01

The manual provides guidelines and procedures for designing bridge deck drainage systems, inclusing illustrative examples. Should the design process indicate a drainage system is needed, utilization of the most hydraulically efficient and maintenance...

Effectiveness evaluation of flood defence structures in different geomorphological contexts

NASA Astrophysics Data System (ADS)

Morelli, Stefano; Pazzi, Veronica; Fanti, Riccardo

2017-04-01

The flood risk in different geomorphological contexts of two less developed countries are investigated in order to evaluate the efficacy of the existing flood defence structures. In particular, a recent floodplain crossed by a wide meandering river and a narrow mountain valley flowed by creek with a torrential regime have been chosen for such analysis in North Albania and central Mexico, respectively. Both areas have been affected by disastrous floods in past years with considerable damages to properties and people. Some safety countermeasures have been performed over time, even if in a non-systematic way. For this reason, the current inclination to flood risk was assessed by means of a freeware software designed to perform one-dimensional (1D) hydraulic modelling for a full network of natural and anthropic channels (HEC-RAS software by Hydrologic Engineering Center River Analysis System). This new analyses take into account: i) the natural morphological variability along the river path, ii) the anthropic interventions on the fluvial dynamics, iii) the landscape appearance after the soil exploitation in the past years, and iv) all the changes induced by an exceeded informal urbanization. The reconstruction of the river and bordering areas geometric data was carried out according to the physical characteristics of the local environment: a bathymetric survey and near-river DGPS acquisitions for the open spaces of the Albanian floodplain, and traditional topographic methods for the highly vegetated Mexican valley. In both cases, the results show that the existing works are, on their own, poorly efficient in containing the predictable floods. Albanians levees seem underdimensioned, while the channelling works are too narrow to contain large amounts of water and solid transport as typical of the Mexican study area. Evidently, a new territorial planning is required in these areas, and some projects are now in place. However, it would be desirable that local authorities were profitably inspired by the criticalities here mentioned.

A cross-sectional study examining the expression of splice variants K-RAS4A and K-RAS4B in advanced non-small-cell lung cancer patients.

PubMed

Aran, Veronica; Masson Domingues, Pedro; Carvalho de Macedo, Fabiane; Moreira de Sousa, Carlos Augusto; Caldas Montella, Tatiane; de Souza Accioly, Maria Theresa; Ferreira, Carlos Gil

2018-02-01

Mammalian cells differently express 4 RAS isoforms: H-RAS, N-RAS, K-RAS4A and K-RAS4B, which are important in promoting oncogenic processes when mutated. In lung cancer, the K-RAS isoform is the most frequently altered RAS protein, being also a difficult therapeutic target. Interestingly, there are two K-RAS splice variants (K-RAS4A and K-RAS4B) and little is known about the role of K-RAS4A. Most studies targeting K-RAS, or analysing it as a prognostic factor, have not taken into account the two isoforms. Consequently, the in-depth investigation of them is needed. The present study analysed 98 specimens from advanced non-small cell lung cancer (NSCLC) adenocarcinoma patients originated from Brazil. The alterations present in K-RAS at the DNA level (Sanger sequencing) as well as the expression of the splicing isoforms at the RNA (qRT-PCR) and protein levels (immunohistochemistry analysis), were evaluated. Possible associations between clinicopathological features and the molecular findings were also investigated. Our results showed that in the non-smoking population, the cancer incidence was higher among women. In contrast, in smokers and former smokers, the incidence was higher among men. Regarding sequencing results, 10.5% of valid samples presented mutations in exon 2, being all wild-type for exon 3, and the most frequently occurring base change was the transversion G → T. Our qRT-PCR and immunohistochemical analysis showed that both, K-RAS4A and K-RAS4B, were differently expressed in NSCLC tumour samples. For example, tumour specimens showed higher K-RAS4A mRNA expression in relation to commercial normal lung control than did K-RAS4B. In addition, K-RAS4B protein expression was frequently stronger than K-RAS4A in the patients analysed. Our results highlight the differential expression of K-RAS4A and K-RAS4B in advanced adenocarcinoma NSCLC patients and underline the need to further clarify the enigma behind their biological significance in various cancer types, including NSCLC. Copyright © 2017 Elsevier B.V. All rights reserved.

LANDSAT technology transfer to the private and public sectors through community colleges and other locally available institutions, phase 2 program

NASA Technical Reports Server (NTRS)

Rogers, R. H. (Principal Investigator)

1982-01-01

A program established by NASA with the Environmental Research Institute of Michigan (ERIM) applies a network where the major participants are NASA, universities or research institutes, community colleges, and local private and public organizations. Local users are given an opportunity to obtain "hands on" training in LANDSAT data analysis and Geographic Information System (GIS) techniques using a desk top, interactive remote analysis station (RAS). The RAS communicates with a central computing facility via telephone line, and provides for generation of land use and land suitability maps and other data products via remote command. During the period from 22 September 1980 - 6 March 1982, 15 workshops and other training activities were successfully conducted throughout Michigan providing hands on training on the RAS terminals for 250 or more people and user awareness activities such as exhibits and demonstrations for 2,000 or more participants.

Coupled excitable Ras and F-actin activation mediates spontaneous pseudopod formation and directed cell movement

PubMed Central

van Haastert, Peter J. M.; Keizer-Gunnink, Ineke; Kortholt, Arjan

2017-01-01

Many eukaryotic cells regulate their mobility by external cues. Genetic studies have identified >100 components that participate in chemotaxis, which hinders the identification of the conceptual framework of how cells sense and respond to shallow chemical gradients. The activation of Ras occurs during basal locomotion and is an essential connector between receptor and cytoskeleton during chemotaxis. Using a sensitive assay for activated Ras, we show here that activation of Ras and F-actin forms two excitable systems that are coupled through mutual positive feedback and memory. This coupled excitable system leads to short-lived patches of activated Ras and associated F-actin that precede the extension of protrusions. In buffer, excitability starts frequently with Ras activation in the back/side of the cell or with F-actin in the front of the cell. In a shallow gradient of chemoattractant, local Ras activation triggers full excitation of Ras and subsequently F-actin at the side of the cell facing the chemoattractant, leading to directed pseudopod extension and chemotaxis. A computational model shows that the coupled excitable Ras/F-actin system forms the driving heart for the ordered-stochastic extension of pseudopods in buffer and for efficient directional extension of pseudopods in chemotactic gradients. PMID:28148648

Flood area and damage estimation in Zhejiang, China.

PubMed

Liu, Renyi; Liu, Nan

2002-09-01

A GIS-based method to estimate flood area and damage is presented in this paper, which is oriented to developing countries like China, where labor is readily available for GIS data collecting, and tools such as, HEC-GeoRAS might not be readily available. At present local authorities in developing countries are often not predisposed to pay for commercial GIS platforms. To calculate flood area, two cases, non-source flood and source flood, are distinguished and a seed-spread algorithm suitable for source-flooding is described. The flood damage estimation is calculated in raster format by overlaying the flood area range with thematic maps and relating this to other socioeconomic data. Several measures used to improve the geometric accuracy and computing efficiency are presented. The management issues related to the application of this method, including the cost-effectiveness of approximate method in practice and supplementing two technical lines (self-programming and adopting commercial GIS software) to each other, are also discussed. The applications show that this approach has practical significance to flood fighting and control in developing countries like China.

Development of a 3D Stream Network and Topography for Improved Large-Scale Hydraulic Modeling

NASA Astrophysics Data System (ADS)

Saksena, S.; Dey, S.; Merwade, V.

2016-12-01

Most digital elevation models (DEMs) used for hydraulic modeling do not include channel bed elevations. As a result, the DEMs are complimented with additional bathymetric data for accurate hydraulic simulations. Existing methods to acquire bathymetric information through field surveys or through conceptual models are limited to reach-scale applications. With an increasing focus on large scale hydraulic modeling of rivers, a framework to estimate and incorporate bathymetry for an entire stream network is needed. This study proposes an interpolation-based algorithm to estimate bathymetry for a stream network by modifying the reach-based empirical River Channel Morphology Model (RCMM). The effect of a 3D stream network that includes river bathymetry is then investigated by creating a 1D hydraulic model (HEC-RAS) and 2D hydrodynamic model (Integrated Channel and Pond Routing) for the Upper Wabash River Basin in Indiana, USA. Results show improved simulation of flood depths and storage in the floodplain. Similarly, the impact of river bathymetry incorporation is more significant in the 2D model as compared to the 1D model.

Assessing and optimising flood control options along the Arachthos river floodplain (Epirus, Greece)

NASA Astrophysics Data System (ADS)

Drosou, Athina; Dimitriadis, Panayiotis; Lykou, Archontia; Kossieris, Panagiotis; Tsoukalas, Ioannis; Efstratiadis, Andreas; Mamassis, Nikos

2015-04-01

We present a multi-criteria simulation-optimization framework for the optimal design and setting of flood protection structures along river banks. The methodology is tested in the lower course of the Arachthos River (Epirus, Greece), downstream of the hydroelectric dam of Pournari. The entire study area is very sensitive, particularly because the river crosses the urban area of Arta, which is located just after the dam. Moreover, extended agricultural areas that are crucial for the local economy are prone to floods. In the proposed methodology we investigate two conflicting criteria, i.e. the minimization of flood hazards (due to damages to urban infrastructures, crops, etc.) and the minimization of construction costs of the essential hydraulic structures (e.g. dikes). For the hydraulic simulation we examine two flood routing models, named 1D HEC-RAS and quasi-2D LISFLOOD, whereas the optimization is carried out through the Surrogate-Enhanced Evolutionary Annealing-Simplex (SE-EAS) algorithm that couples the strengths of surrogate modeling with the effectiveness and efficiency of the EAS method.

[Estimation of spur dike-affected fish habitat area].

PubMed

Ray-Shyan, Wu; Yan-Ru, Chen; Yi-Liang, Ge

2012-04-01

Based on the HEC-RAS and River 2D modes, and taking 5% change rate of weighted usable area (WUA) as the threshold to define the spur dike- affected area of target fish species Acrossocheilus paradoxus in Fazi River in Taiwan, this paper studied the affected area of the fish habitat by spur dike, and, in combining with the references about the installations of spur dikes in Taiwan in recent 10 years, analyzed the relative importance of related affecting factors such as dike height, dike length (water block rate), average slope gradient of river way, single or double spur dike, and flow discharge. In spite of the length of the dike, the affected area in downstream was farther, and was about 2-6 times as large as that in upstream. The ratio of the affected area in downstream / upstream decreased with increasing slope gradient, but increased with increasing dike length and flow discharge. When the discharge was approximate to 10 years return periods, the ratio of the affected area would be close to a constant of 2. Building double spur dike would produce a better WUA than building single spur dike.

The optimization of high resolution topographic data for 1D hydrodynamic models

NASA Astrophysics Data System (ADS)

Ales, Ronovsky; Michal, Podhoranyi

2016-06-01

The main focus of our research presented in this paper is to optimize and use high resolution topographical data (HRTD) for hydrological modelling. Optimization of HRTD is done by generating adaptive mesh by measuring distance of coarse mesh and the surface of the dataset and adapting the mesh from the perspective of keeping the geometry as close to initial resolution as possible. Technique described in this paper enables computation of very accurate 1-D hydrodynamic models. In the paper, we use HEC-RAS software as a solver. For comparison, we have chosen the amount of generated cells/grid elements (in whole discretization domain and selected cross sections) with respect to preservation of the accuracy of the computational domain. Generation of the mesh for hydrodynamic modelling is strongly reliant on domain size and domain resolution. Topographical dataset used in this paper was created using LiDAR method and it captures 5.9km long section of a catchment of the river Olše. We studied crucial changes in topography for generated mesh. Assessment was done by commonly used statistical and visualization methods.

The optimization of high resolution topographic data for 1D hydrodynamic models

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

Ales, Ronovsky, E-mail: ales.ronovsky@vsb.cz; Michal, Podhoranyi

2016-06-08

The main focus of our research presented in this paper is to optimize and use high resolution topographical data (HRTD) for hydrological modelling. Optimization of HRTD is done by generating adaptive mesh by measuring distance of coarse mesh and the surface of the dataset and adapting the mesh from the perspective of keeping the geometry as close to initial resolution as possible. Technique described in this paper enables computation of very accurate 1-D hydrodynamic models. In the paper, we use HEC-RAS software as a solver. For comparison, we have chosen the amount of generated cells/grid elements (in whole discretization domainmore » and selected cross sections) with respect to preservation of the accuracy of the computational domain. Generation of the mesh for hydrodynamic modelling is strongly reliant on domain size and domain resolution. Topographical dataset used in this paper was created using LiDAR method and it captures 5.9km long section of a catchment of the river Olše. We studied crucial changes in topography for generated mesh. Assessment was done by commonly used statistical and visualization methods.« less

Hydrologic and Hydraulic Analyses of Selected Streams in Lorain County, Ohio, 2003

USGS Publications Warehouse

Jackson, K. Scott; Ostheimer, Chad J.; Whitehead, Matthew T.

2003-01-01

Hydrologic and hydraulic analyses were done for selected reaches of nine streams in Lorain County Ohio. To assess the alternatives for flood-damage mitigation, the Lorain County Engineer and the U.S. Geological Survey (USGS) initiated a cooperative study to investigate aspects of the hydrology and hydraulics of the nine streams. Historical streamflow data and regional regression equations were used to estimate instantaneous peak discharges for floods having recurrence intervals of 2, 5, 10, 25, 50, and 100 years. Explanatory variables used in the regression equations were drainage area, main-channel slope, and storage area. Drainage areas of the nine stream reaches studied ranged from 1.80 to 19.3 square miles. The step-backwater model HEC-RAS was used to determine water-surface-elevation profiles for the 10-year-recurrence-interval (10-year) flood along a selected reach of each stream. The water-surface pro-file information was used then to generate digital mapping of flood-plain boundaries. The analyses indicate that at the 10-year flood elevation, road overflow results at numerous hydraulic structures along the nine streams.

Habitable evaporated cores: transforming mini-Neptunes into super-Earths in the habitable zones of M dwarfs.

PubMed

Luger, R; Barnes, R; Lopez, E; Fortney, J; Jackson, B; Meadows, V

2015-01-01

We show that photoevaporation of small gaseous exoplanets ("mini-Neptunes") in the habitable zones of M dwarfs can remove several Earth masses of hydrogen and helium from these planets and transform them into potentially habitable worlds. We couple X-ray/extreme ultraviolet (XUV)-driven escape, thermal evolution, tidal evolution, and orbital migration to explore the types of systems that may harbor such "habitable evaporated cores" (HECs). We find that HECs are most likely to form from planets with ∼1 M⊕ solid cores with up to about 50% H/He by mass, though whether or not a given mini-Neptune forms a HEC is highly dependent on the early XUV evolution of the host star. As terrestrial planet formation around M dwarfs by accumulation of local material is likely to form planets that are small and dry, evaporation of small migrating mini-Neptunes could be one of the dominant formation mechanisms for volatile-rich Earths around these stars.

Effect of sieving polymer concentration on separation of 100 bp DNA Ladder by capillary gel electrophoresis

NASA Astrophysics Data System (ADS)

Nakazumi, T.; Hara, Y.

2017-09-01

We studied the effect of sieving polymer concentration on separation of a 100 bp DNA Ladder by capillary gel electrophoresis (CGE) using hydroxyethyl cellulose (HEC) with a molecular size of 1000 k. For measurement purposes, we selected a fused silica capillary with total length of 15 cm and effective length of 7.5 cm; this was applied to compact CGE equipment for a Point-Care-Testing (POCT) system. Measurement results of the 100 bp DNA Ladder sample indicated that small DNA separation was significantly affected by HEC sieving polymer concentration. This was due to the level of entanglement between small DNA molecules and the sieving polymer chain significantly influencing migration time, mobility, and resolution length of the CGE process. We concluded that 1.0 w/v % HEC sieving polymer concentration was optimal for CGE separation of DNA ≥1000bp in the 100 bp DNA Ladder (100-1500 bp) when using the short-length capillary.

Evaluation of transplant renal artery blood flow by Doppler sound-spectrum analysis.

PubMed

Reinitz, E R; Goldman, M H; Sais, J; Rittgers, S E; Lee, H M; Mendez-Picon, G; Muakkassa, W F; Barnes, R W

1983-04-01

Doppler ultrasonography sound-spectrum analysis (SSA) was used to evaluate blood flow in the transplanted kidney and its renal artery. Seven patients with posttransplant hypertension and a bruit over the transplanted kidney were screened for renal artery stenosis (RAS). In five patients, RAS was diagnosed by SSA, and in two it was not. These findings were confirmed by subsequent angiography in all patients. Three patients studied after surgical correction of their RAS had improvement in their SSA patterns. Fourteen hypertensive patients with a cause other than RAS were evaluated by SSA. None of them had SSA findings suggestive of RAS. Doppler ultrasonography with SSA is an effective, noninvasive technique of monitoring transplant renal blood flow, especially in the screening of hypertensive transplant recipients for transplant RAS.

Development and validation of an automated delirium risk assessment system (Auto-DelRAS) implemented in the electronic health record system.

PubMed

Moon, Kyoung-Ja; Jin, Yinji; Jin, Taixian; Lee, Sun-Mi

2018-01-01

A key component of the delirium management is prevention and early detection. To develop an automated delirium risk assessment system (Auto-DelRAS) that automatically alerts health care providers of an intensive care unit (ICU) patient's delirium risk based only on data collected in an electronic health record (EHR) system, and to evaluate the clinical validity of this system. Cohort and system development designs were used. Medical and surgical ICUs in two university hospitals in Seoul, Korea. A total of 3284 patients for the development of Auto-DelRAS, 325 for external validation, 694 for validation after clinical applications. The 4211 data items were extracted from the EHR system and delirium was measured using CAM-ICU (Confusion Assessment Method for Intensive Care Unit). The potential predictors were selected and a logistic regression model was established to create a delirium risk scoring algorithm to construct the Auto-DelRAS. The Auto-DelRAS was evaluated at three months and one year after its application to clinical practice to establish the predictive validity of the system. Eleven predictors were finally included in the logistic regression model. The results of the Auto-DelRAS risk assessment were shown as high/moderate/low risk on a Kardex screen. The predictive validity, analyzed after the clinical application of Auto-DelRAS after one year, showed a sensitivity of 0.88, specificity of 0.72, positive predictive value of 0.53, negative predictive value of 0.94, and a Youden index of 0.59. A relatively high level of predictive validity was maintained with the Auto-DelRAS system, even one year after it was applied to clinical practice. Copyright © 2017. Published by Elsevier Ltd.

1D and 2D urban dam-break flood modelling in Istanbul, Turkey

NASA Astrophysics Data System (ADS)

Ozdemir, Hasan; Neal, Jeffrey; Bates, Paul; Döker, Fatih

2014-05-01

Urban flood events are increasing in frequency and severity as a consequence of several factors such as reduced infiltration capacities due to continued watershed development, increased construction in flood prone areas due to population growth, the possible amplification of rainfall intensity due to climate change, sea level rise which threatens coastal development, and poorly engineered flood control infrastructure (Gallegos et al., 2009). These factors will contribute to increased urban flood risk in the future, and as a result improved modelling of urban flooding according to different causative factor has been identified as a research priority (Gallegos et al., 2009; Ozdemir et al. 2013). The flooding disaster caused by dam failures is always a threat against lives and properties especially in urban environments. Therefore, the prediction of dynamics of dam-break flows plays a vital role in the forecast and evaluation of flooding disasters, and is of long-standing interest for researchers. Flooding occurred on the Ayamama River (Istanbul-Turkey) due to high intensity rainfall and dam-breaching of Ata Pond in 9th September 2009. The settlements, industrial areas and transportation system on the floodplain of the Ayamama River were inundated. Therefore, 32 people were dead and millions of Euros economic loses were occurred. The aim of this study is 1 and 2-Dimensional flood modelling of the Ata Pond breaching using HEC-RAS and LISFLOOD-Roe models and comparison of the model results using the real flood extent. The HEC-RAS model solves the full 1-D Saint Venant equations for unsteady open channel flow whereas LISFLOOD-Roe is the 2-D shallow water model which calculates the flow according to the complete Saint Venant formulation (Villanueva and Wright, 2006; Neal et al., 2011). The model consists a shock capturing Godunov-type scheme based on the Roe Riemann solver (Roe, 1981). 3 m high resolution Digital Surface Model (DSM), natural characteristics of the pond and its breaching such as depth, wide, length, volume and breaching shape and daily total rainfall data were used in the models. The simulated flooding in the both models were compared with the real flood extent which gathered from photos taken after the flood event, high satellite images acquired after 20 days from the flood event, and field works. The results show that LISFLOOD-Roe hydraulic model gives more than 80% fit to the extent of real flood event. Also both modelling results show that the embankment breaching of the Ata Pond directly affected the flood magnitude and intensity on the area. This study reveals that modelling of the probable flooding in urban areas is necessary and very important in urban planning. References Gallegos, H. A., Schubert, J. E., and Sanders, B. F.: Two dimensional, high-resolution modeling of urban dam-break flooding: A case study of Baldwin Hills California, Adv. Water Resour., 32, 1323-1335, 2009. Neal, J., Villanueva, I., Wright, N., Willis, T., Fewtrell, T. and Bates, P.: How mush physical complexity is needed to model flood inundation? Hydrological Processes, DOI: 10.1002/hyp.8339. Ozdemir H., Sampson C., De Almeida G., Bates P.D.: Evaluating scale and roughness effects in urban flood modelling using terrestrial LiDAR data, Hydrology and Earth System Sciences, vol.17, pp.4015-4030, 2013. Roe P.: Approximate Riemann solvers, parameter vectors, and difference-schemes. Journal of Computational Physics 43(2): 357-372, 1981. Villanueva I, Wright NG.: Linking Riemann and storage cell models for flood prediction. Proceedings of the Institution of Civil Engineers, Journal of Water Management 159: 27-33, 2006.

Recovery of phenotypes obtained by adaptive evolution through inverse metabolic engineering.

PubMed

Hong, Kuk-Ki; Nielsen, Jens

2012-11-01

In a previous study, system level analysis of adaptively evolved yeast mutants showing improved galactose utilization revealed relevant mutations. The governing mutations were suggested to be in the Ras/PKA signaling pathway and ergosterol metabolism. Here, site-directed mutants having one of the mutations RAS2(Lys77), RAS2(Tyr112), and ERG5(Pro370) were constructed and evaluated. The mutants were also combined with overexpression of PGM2, earlier proved as a beneficial target for galactose utilization. The constructed strains were analyzed for their gross phenotype, transcriptome and targeted metabolites, and the results were compared to those obtained from reference strains and the evolved strains. The RAS2(Lys77) mutation resulted in the highest specific galactose uptake rate among all of the strains with an increased maximum specific growth rate on galactose. The RAS2(Tyr112) mutation also improved the specific galactose uptake rate and also resulted in many transcriptional changes, including ergosterol metabolism. The ERG5(Pro370) mutation only showed a small improvement, but when it was combined with PGM2 overexpression, the phenotype was almost the same as that of the evolved mutants. Combination of the RAS2 mutations with PGM2 overexpression also led to a complete recovery of the adaptive phenotype in galactose utilization. Recovery of the gross phenotype by the reconstructed mutants was achieved with much fewer changes in the genome and transcriptome than for the evolved mutants. Our study demonstrates how the identification of specific mutations by systems biology can direct new metabolic engineering strategies for improving galactose utilization by yeast.

A Histidine pH sensor regulates activation of the Ras-specific guanine nucleotide exchange factor RasGRP1.

PubMed

Vercoulen, Yvonne; Kondo, Yasushi; Iwig, Jeffrey S; Janssen, Axel B; White, Katharine A; Amini, Mojtaba; Barber, Diane L; Kuriyan, John; Roose, Jeroen P

2017-09-27

RasGRPs are guanine nucleotide exchange factors that are specific for Ras or Rap, and are important regulators of cellular signaling. Aberrant expression or mutation of RasGRPs results in disease. An analysis of RasGRP1 SNP variants led to the conclusion that the charge of His 212 in RasGRP1 alters signaling activity and plasma membrane recruitment, indicating that His 212 is a pH sensor that alters the balance between the inactive and active forms of RasGRP1. To understand the structural basis for this effect we compared the structure of autoinhibited RasGRP1, determined previously, to those of active RasGRP4:H-Ras and RasGRP2:Rap1b complexes. The transition from the autoinhibited to the active form of RasGRP1 involves the rearrangement of an inter-domain linker that displaces inhibitory inter-domain interactions. His 212 is located at the fulcrum of these conformational changes, and structural features in its vicinity are consistent with its function as a pH-dependent switch.

Structural analysis of autoinhibition in the Ras-specific exchange factor RasGRP1

PubMed Central

Iwig, Jeffrey S; Vercoulen, Yvonne; Das, Rahul; Barros, Tiago; Limnander, Andre; Che, Yan; Pelton, Jeffrey G; Wemmer, David E; Roose, Jeroen P; Kuriyan, John

2013-01-01

RasGRP1 and SOS are Ras-specific nucleotide exchange factors that have distinct roles in lymphocyte development. RasGRP1 is important in some cancers and autoimmune diseases but, in contrast to SOS, its regulatory mechanisms are poorly understood. Activating signals lead to the membrane recruitment of RasGRP1 and Ras engagement, but it is unclear how interactions between RasGRP1 and Ras are suppressed in the absence of such signals. We present a crystal structure of a fragment of RasGRP1 in which the Ras-binding site is blocked by an interdomain linker and the membrane-interaction surface of RasGRP1 is hidden within a dimerization interface that may be stabilized by the C-terminal oligomerization domain. NMR data demonstrate that calcium binding to the regulatory module generates substantial conformational changes that are incompatible with the inactive assembly. These features allow RasGRP1 to be maintained in an inactive state that is poised for activation by calcium and membrane-localization signals. DOI: http://dx.doi.org/10.7554/eLife.00813.001 PMID:23908768

Subcellular characteristics of functional intracellular renin–angiotensin systems☆

PubMed Central

Abadir, Peter M.; Walston, Jeremy D.; Carey, Robert M.

2013-01-01

The renin–angio tensin system (RAS) is now regarded as an integral component in not only the development of hypertension, but also in physiologic and pathophysiologic mechanisms in multiple tissues and chronic disease states. While many of the endocrine (circulating), paracrine (cell-to-different cell) and autacrine (cell-to-same cell) effects of the RAS are believed to be mediated through the canonical extracellular RAS, a complete, independent and differentially regulated intracellular RAS (iRAS) has also been proposed. Angiotensinogen, the enzymes renin and angiotensin-converting enzyme (ACE) and the angiotensin peptides can all be synthesized and retained intracellularly. Angiotensin receptors (types I and 2) are also abundant intracellularly mainly at the nuclear and mitochondrial levels. The aim of this review is to focus on the most recent information concerning the subcellular localization, distribution and functions of the iRAS and to discuss the potential consequences of activation of the subcellular RAS on different organ systems. PMID:23032352

Helium isotope, C/3He, and Ba-Nb-Ti signatures in the northern Lau Basin: Distinguishing arc, back-arc, and hotspot affinities

NASA Astrophysics Data System (ADS)

Lupton, John; Rubin, Ken H.; Arculus, Richard; Lilley, Marvin; Butterfield, David; Resing, Joseph; Baker, Edward; Embley, Robert

2015-04-01

The northern Lau Basin hosts a complicated pattern of volcanism, including Tofua Arc volcanoes, several back-arc spreading centers, and individual "rear-arc" volcanoes not associated with these structures. Elevated 3He/4He ratios in lavas of the NW Lau Spreading Center suggest the influence of a mantle plume, possibly from Samoa. We show that lavas from mid-ocean ridges, volcanic arcs, and hotspots occupy distinct, nonoverlapping fields in a 3He/4He versus C/3He plot. Applied to the northern Lau Basin, this approach shows that most of Lau back-arc spreading systems have mid-ocean ridge 3He/4He-C/3He characteristics, except the NW Lau spreading center, which has 3He/4He-C/3He similar to "high 3He" hotspots such as Loihi, Kilauea, and Yellowstone, but with slightly lower C/3He. Niua seamount, on the northern extension of the Tofua Arc, falls squarely in the arc field. All the NE Lau rear-arc volcanoes, including the recently erupting West Mata, also have arc-like 3He/4He-C/3He characteristics. Ba-Nb-Ti contents of the lavas, which are more traditional trace element indicators of mantle source enrichment, depletion, and subduction input, likewise indicate arc and hot spot influences in the lavas of the northern Lau Basin, but in a more ambiguous fashion because of a complex prior history. This verifies that 3He/4He-C/3He systematics are useful for differentiating between mid-ocean ridge, arc, and hotspot affinities in submarine volcanic systems, that all three of these affinities are expressed in the northern Lau Basin, and provides additional support for the Samoan plume influence in the region.

Integrating a Typhoon Event Database with an Optimal Flood Operation Model on the Real-Time Flood Control of the Tseng-Wen Reservoir

NASA Astrophysics Data System (ADS)

Chen, Y. W.; Chang, L. C.

2012-04-01

Typhoons which normally bring a great amount of precipitation are the primary natural hazard in Taiwan during flooding season. Because the plentiful rainfall quantities brought by typhoons are normally stored for the usage of the next draught period, the determination of release strategies for flood operation of reservoirs which is required to simultaneously consider not only the impact of reservoir safety and the flooding damage in plain area but also for the water resource stored in the reservoir after typhoon becomes important. This study proposes a two-steps study process. First, this study develop an optimal flood operation model (OFOM) for the planning of flood control and also applies the OFOM on Tseng-wun reservoir and the downstream plain related to the reservoir. Second, integrating a typhoon event database with the OFOM mentioned above makes the proposed planning model have ability to deal with a real-time flood control problem and names as real-time flood operation model (RTFOM). Three conditions are considered in the proposed models, OFOM and RTFOM, include the safety of the reservoir itself, the reservoir storage after typhoons and the impact of flooding in the plain area. Besides, the flood operation guideline announced by government is also considered in the proposed models. The these conditions and the guideline can be formed as an optimization problem which is solved by the genetic algorithm (GA) in this study. Furthermore, a distributed runoff model, kinematic-wave geomorphic instantaneous unit hydrograph (KW-GIUH), and a river flow simulation model, HEC-RAS, are used to simulate the river water level of Tseng-wun basin in the plain area and the simulated level is shown as an index of the impact of flooding. Because the simulated levels are required to re-calculate iteratively in the optimization model, applying a recursive artificial neural network (recursive ANN) instead of the HEC-RAS model can significantly reduce the computational burden of the entire optimization problem. This study applies the developed methodology to Tseng-wun Reservoir. Forty typhoon events are collected as the historical database and six typhoon events are used to verify the proposed model. These typhoons include Typhoon Sepat and Typhoon Korsa in 2007 and Typhoon Kalmaegi, Typhoon Fung-Wong, Typhoon Sinlaku and Typhoon Jangmi in 2008. The results show that the proposed model can reduce the flood duration at the downstream area. For example, the real-time flood control model can reduce the flood duration by four and three hours for Typhoon Korsa and Typhoon Sinlaku respectively. This results indicate that the developed model can be a very useful tool for real-time flood control operation of reservoirs.

Aerodynamic Comparison of Hyper-Elliptic Cambered Span (HECS) Wings with Conventional Configurations

NASA Technical Reports Server (NTRS)

Lazos, Barry S.; Visser, Kenneth D.

2006-01-01

An experimental study was conducted to examine the aerodynamic and flow field characteristics of hyper-elliptic cambered span (HECS) wings and compare results with more conventional configurations used for induced drag reduction. Previous preliminary studies, indicating improved L/D characteristics when compared to an elliptical planform prompted this more detailed experimental investigation. Balance data were acquired on a series of swept and un-swept HECS wings, a baseline elliptic planform, two winglet designs and a raked tip configuration. Seven-hole probe wake surveys were also conducted downstream of a number of the configurations. Wind tunnel results indicated aerodynamic performance levels of all but one of the HECS wings exceeded that of the other configurations. The flow field data surveys indicate the HECS configurations displaced the tip vortex farther outboard of the wing than the Baseline configuration. Minimum drag was observed on the raked tip configuration and it was noted that the winglet wake lacked the cohesive vortex structure present in the wakes of the other configurations.

Impact of 5-HT3 receptor antagonists on chemotherapy-induced nausea and vomiting: a retrospective cohort study

PubMed Central

2012-01-01

Background 1st generation 5-hydroxytryptamine receptor antagonists (5-HT3 RAs), and palonosetron, a 2nd generation 5-HT3 RA, are indicated for the prevention of chemotherapy (CT)-induced nausea and vomiting (CINV) associated with moderately (MEC) and highly emetogenic CT agents (HEC). This study explores the impact of step therapy policies requiring use of an older 5-HT3 RA before palonosetron on risk of CINV associated with hospital or emergency department (ED) admissions. Methods Patients who received cyclophosphamide post breast cancer (BC) surgery or who were diagnosed with lung cancer on carboplatin (LC-carboplatin) or cisplatin (LC-cisplatin) were selected from PharMetrics’ (IMS LifeLink) claims dataset (2005-2008). Patients were followed for 6 months from initial CT administration for CINV events identified through ICD-9-CM codes. Patients were grouped into those initiated with older, generic 5-HT3 RAs (ondansetron, granisetron, and dolasetron) and those initiated and maintained on palonosetron throughout study follow-up. CINV events and CINV days were analyzed using multivariate regressions controlling for demographic and clinical variables. Results Eligible patients numbered 3,606 in BC, 4,497 in LC-carboplatin and 1,154 in LC-cisplatin cohorts, with 52%, 40%, and 34% in the palonosetron group, respectively. There was no significant difference between the two 5-HT3 RA groups in age or Charlson Comorbidity Index among the two MEC cohorts (BC and LC-carboplatin). Among the LC-cisplatin cohort, palonosetron users were older with more males than the older 5-HT3 RA group (age: 60.1 vs. 61.3; males, 66.9% vs. 56.9%). Compared to the older 5-HT3 RAs, the palonosetron groups incurred 22%-51% fewer 5-HT3 RA pharmacy claims, had fewer patients with CINV events (3.5% vs. 5.5% in BC, 9.5% vs. 12.8% in LC-carboplatin, 16.4% vs. 21.7% in LC-cisplatin), and had lower risk for CINV events (odds ratios 0.62, 0.71, or 0.71, respectively; p < 0.05). The BC and LC-carboplatin palonosetron groups experienced 50% and 30% fewer CINV days than the generic 5-HT3 RA group (p < 0.05). Conclusions Patients with breast or lung cancer initiated and maintained on palonosetron were at significantly lower risk for potentially costly CINV versus those on older 5-HT3 RAs. Further studies on impact of step therapy policy are warranted in order to minimize the clinical and economic burden of CINV. PMID:22823909

Impact of 5-HT3 receptor antagonists on chemotherapy-induced nausea and vomiting: a retrospective cohort study.

PubMed

Lin, Swu-Jane; Hatoum, Hind T; Buchner, Deborah; Cox, David; Balu, Sanjeev

2012-07-23

1st generation 5-hydroxytryptamine receptor antagonists (5-HT3 RAs), and palonosetron, a 2nd generation 5-HT3 RA, are indicated for the prevention of chemotherapy (CT)-induced nausea and vomiting (CINV) associated with moderately (MEC) and highly emetogenic CT agents (HEC). This study explores the impact of step therapy policies requiring use of an older 5-HT3 RA before palonosetron on risk of CINV associated with hospital or emergency department (ED) admissions. Patients who received cyclophosphamide post breast cancer (BC) surgery or who were diagnosed with lung cancer on carboplatin (LC-carboplatin) or cisplatin (LC-cisplatin) were selected from PharMetrics' (IMS LifeLink) claims dataset (2005-2008). Patients were followed for 6 months from initial CT administration for CINV events identified through ICD-9-CM codes. Patients were grouped into those initiated with older, generic 5-HT3 RAs (ondansetron, granisetron, and dolasetron) and those initiated and maintained on palonosetron throughout study follow-up. CINV events and CINV days were analyzed using multivariate regressions controlling for demographic and clinical variables. Eligible patients numbered 3,606 in BC, 4,497 in LC-carboplatin and 1,154 in LC-cisplatin cohorts, with 52%, 40%, and 34% in the palonosetron group, respectively. There was no significant difference between the two 5-HT3 RA groups in age or Charlson Comorbidity Index among the two MEC cohorts (BC and LC-carboplatin). Among the LC-cisplatin cohort, palonosetron users were older with more males than the older 5-HT3 RA group (age: 60.1 vs. 61.3; males, 66.9% vs. 56.9%). Compared to the older 5-HT3 RAs, the palonosetron groups incurred 22%-51% fewer 5-HT3 RA pharmacy claims, had fewer patients with CINV events (3.5% vs. 5.5% in BC, 9.5% vs. 12.8% in LC-carboplatin, 16.4% vs. 21.7% in LC-cisplatin), and had lower risk for CINV events (odds ratios 0.62, 0.71, or 0.71, respectively; p<0.05). The BC and LC-carboplatin palonosetron groups experienced 50% and 30% fewer CINV days than the generic 5-HT3 RA group (p<0.05). Patients with breast or lung cancer initiated and maintained on palonosetron were at significantly lower risk for potentially costly CINV versus those on older 5-HT3 RAs. Further studies on impact of step therapy policy are warranted in order to minimize the clinical and economic burden of CINV.

Urinary Angiotensinogen Excretion Level Is Associated With Elevated Blood Pressure in the Normotensive General Population.

PubMed

Sato, Emiko; Wang, An Yi; Satoh, Michihiro; Nishikiori, Yoko; Oba-Yabana, Ikuko; Yoshida, Mai; Sato, Hiroshi; Ito, Sadayoshi; Hida, Wataru; Mori, Takefumi

2018-05-07

Inflammation, intrarenal renin-angiotensin system (RAS) activation, oxidative stress, and carbonyl stress have been postulated to play a fundamental role in controlling blood pressure. However, little is known about the association among renal RAS activation, carbonyl stress, and blood pressure elevation. We evaluated the relationship between blood pressure elevation and either renal RAS activity or carbonyl stress in the general population (N = 355) in Japan. To minimize the effect of antihypertensive drug therapy, we divided participants into 3 groups (normotensive, hypertensive-with-non-medication, and hypertensive-with-medication). Intrarenal RAS activity and carbonyl stress were indicated by the urinary angiotensinogen (AGT) and carbonyl compound excretion levels, respectively. The urinary AGT and carbonyl compound excretion levels were significantly associated with blood pressure. Using a stepwise multiple regression analysis, we found that the urinary AGT excretion levels were strongly associated with blood pressure elevation, compared with inflammation, oxidative stress, and carbonyl stress markers, in all groups. Urinary carbonyl compound excretion was significantly associated with blood pressure in only the hypertensive-without-medication group. Furthermore, blood pressure was significantly increased in these participants, and both the urinary AGT and carbonyl compound levels were high. The urinary AGT excretion levels were strongly associated with elevated blood pressure in normotensive people, and inappropriate renal RAS activity and carbonyl stress independently contributed to the development of hypertension. These findings suggest that RAS activation, particularly renal RAS activation exert a fundamental role in the pathogenesis of hypertension in the general population.

The NM23-H1/H2 homolog NDK-1 is required for full activation of Ras signaling in C. elegans

PubMed Central

Masoudi, Neda; Fancsalszky, Luca; Pourkarimi, Ehsan; Vellai, Tibor; Alexa, Anita; Reményi, Attila; Gartner, Anton; Mehta, Anil; Takács-Vellai, Krisztina

2013-01-01

The group I members of the Nm23 (non-metastatic) gene family encode nucleoside diphosphate kinases (NDPKs) that have been implicated in the regulation of cell migration, proliferation and differentiation. Despite their developmental and medical significance, the molecular functions of these NDPKs remain ill defined. To minimize confounding effects of functional compensation between closely related Nm23 family members, we studied ndk-1, the sole Caenorhabditis elegans ortholog of group I NDPKs, and focused on its role in Ras/mitogen-activated protein kinase (MAPK)-mediated signaling events during development. ndk-1 inactivation leads to a protruding vulva phenotype and affects vulval cell fate specification through the Ras/MAPK cascade. ndk-1 mutant worms show severe reduction of activated, diphosphorylated MAPK in somatic tissues, indicative of compromised Ras/MAPK signaling. A genetic epistasis analysis using the vulval induction system revealed that NDK-1 acts downstream of LIN-45/Raf, but upstream of MPK-1/MAPK, at the level of the kinase suppressors of ras (KSR-1/2). KSR proteins act as scaffolds facilitating Ras signaling events by tethering signaling components, and we suggest that NDK-1 modulates KSR activity through direct physical interaction. Our study reveals that C. elegans NDK-1/Nm23 influences differentiation by enhancing the level of Ras/MAPK signaling. These results might help to better understand how dysregulated Nm23 in humans contributes to tumorigenesis. PMID:23900546

Identification of Ras-degrading small molecules that inhibit the transformation of colorectal cancer cells independent of β-catenin signaling.

PubMed

Shin, Wookjin; Lee, Sang-Kyu; Hwang, Jeong-Ha; Park, Jong-Chan; Cho, Yong-Hee; Ro, Eun Ji; Song, Yeonhwa; Seo, Haeng Ran; Choi, Kang-Yell

2018-06-06

Although the development of drugs that control Ras is an emerging topic in cancer therapy, no clinically applicable drug is currently available. We have previously utilized knowledge of the Wnt/β-catenin signaling-dependent mechanism of Ras protein stability regulation to identify small molecules that inhibit the proliferation and transformation of various colorectal cancer (CRC) cells via degradation of both β-catenin and Ras. Due to the absence of Ras degradation in cells expressing a nondegradable mutant form of β-catenin and the need to determine an alternative mechanism of Ras degradation, we designed a cell-based system to screen compounds that degrade Ras independent of the Wnt/β-catenin signaling pathway. A cell-based high-content screening (HCS) system that monitors the levels of EGFP-K-Ras G12V was established using HCT-116 cells harboring a nondegradable mutant CTNNB1 (ΔS45). Through HCS of a chemical library composed of 10,000 compounds and subsequent characterization of hits, we identified several compounds that degrade Ras without affecting the β-catenin levels. KY7749, one of the most effective compounds, inhibited the proliferation and transformation of CRC cells, especially KRAS-mutant cells that are resistant to the EGFR monoclonal antibody cetuximab. Small molecules that degrade Ras independent of β-catenin may able to be used in treatments for cancers caused by aberrant EGFR and Ras.

Freshwater Recirculating Aquaculture System Operations Drive Biofilter Bacterial Community Shifts around a Stable Nitrifying Consortium of Ammonia-Oxidizing Archaea and Comammox Nitrospira

PubMed Central

Bartelme, Ryan P.; McLellan, Sandra L.; Newton, Ryan J.

2017-01-01

Recirculating aquaculture systems (RAS) are unique engineered ecosystems that minimize environmental perturbation by reducing nutrient pollution discharge. RAS typically employ a biofilter to control ammonia levels produced as a byproduct of fish protein catabolism. Nitrosomonas (ammonia-oxidizing), Nitrospira, and Nitrobacter (nitrite-oxidizing) species are thought to be the primary nitrifiers present in RAS biofilters. We explored this assertion by characterizing the biofilter bacterial and archaeal community of a commercial scale freshwater RAS that has been in operation for >15 years. We found the biofilter community harbored a diverse array of bacterial taxa (>1000 genus-level taxon assignments) dominated by Chitinophagaceae (~12%) and Acidobacteria (~9%). The bacterial community exhibited significant composition shifts with changes in biofilter depth and in conjunction with operational changes across a fish rearing cycle. Archaea also were abundant, and were comprised solely of a low diversity assemblage of Thaumarchaeota (>95%), thought to be ammonia-oxidizing archaea (AOA) from the presence of AOA ammonia monooxygenase genes. Nitrosomonas were present at all depths and time points. However, their abundance was >3 orders of magnitude less than AOA and exhibited significant depth-time variability not observed for AOA. Phylogenetic analysis of the nitrite oxidoreductase beta subunit (nxrB) gene indicated two distinct Nitrospira populations were present, while Nitrobacter were not detected. Subsequent identification of Nitrospira ammonia monooxygenase alpha subunit genes in conjunction with the phylogenetic placement and quantification of the nxrB genotypes suggests complete ammonia-oxidizing (comammox) and nitrite-oxidizing Nitrospira populations co-exist with relatively equivalent and stable abundances in this system. It appears RAS biofilters harbor complex microbial communities whose composition can be affected directly by typical system operations while supporting multiple ammonia oxidation lifestyles within the nitrifying consortium. PMID:28194147

Comparison of an extended-release formulation of granisetron (APF530) versus palonosetron for the prevention of chemotherapy-induced nausea and vomiting associated with moderately or highly emetogenic chemotherapy: results of a prospective, randomized, double-blind, noninferiority phase 3 trial.

PubMed

Raftopoulos, Harry; Cooper, William; O'Boyle, Erin; Gabrail, Nashat; Boccia, Ralph; Gralla, Richard J

2015-03-01

Subcutaneous APF530 provides controlled sustained release of granisetron to prevent acute (0-24 h) and delayed (24-120 h) chemotherapy-induced nausea and vomiting (CINV). This randomized, double-blind phase 3 trial compared APF530 and palonosetron in preventing acute and delayed CINV after moderately (MEC) or highly emetogenic chemotherapy (HEC). Patients receiving single-day MEC or HEC received single-dose APF530 250 or 500 mg subcutaneously (SC) (granisetron 5 or 10 mg) or intravenous palonosetron 0.25 mg. Primary objectives were to establish APF530 noninferiority to palonosetron for preventing acute CINV following MEC or HEC and delayed CINV following MEC and to determine APF530 superiority to palonosetron for preventing delayed CINV following HEC. The primary efficacy end point was complete response (CR [using CI difference for APF530-palonosetron]). A lower confidence bound greater than -15 % indicated noninferiority. In the modified intent-to-treat population (MEC = 634; HEC = 707), both APF530 doses were noninferior to palonosetron in preventing acute CINV after MEC (CRs 74.8 % [-9.8, 9.3] and 76.9 % [-7.5, 11.4], respectively, vs. 75.0 % palonosetron) and after HEC (CRs 77.7 % [-11.5, 5.5] and 81.3 % [-7.7, 8.7], respectively, vs. 80.7 % palonosetron). APF530 500 mg was noninferior to palonosetron in preventing delayed CINV after MEC (CR 58.5 % [-9.5, 12.1] vs. 57.2 % palonosetron) but not superior in preventing delayed CINV after HEC. Adverse events were generally mild and unrelated to treatment, the most common (excluding injection-site reactions) being constipation. A single subcutaneous APF530 injection offers a convenient alternative to palonosetron for preventing acute and delayed CINV after MEC or HEC.

Tg.rasH2 Mice and not CByB6F1 Mice Should Be Used for 28-Day Dose Range Finding Studies Prior to 26-Week Tg.rasH2 Carcinogenicity Studies.

PubMed

Paranjpe, Madhav G; Belich, Jessica; Vidmar, Tom J; Elbekai, Reem H; McKeon, Marie; Brown, Caren

Our recent retrospective analysis of data, collected from 29 Tg.rasH2 mouse carcinogenicity studies, determined how successful the strategy of choosing the high dose for the 26-week studies was based on the estimated maximum tolerated dose (EMTD) derived from earlier 28-day dose range finding (DRF) studies conducted in CByB6F1 mice. Our analysis demonstrated that the high doses applied at EMTD in the 26-week Tg.rasH2 studies failed to detect carcinogenic effects. To investigate why the dose selection process failed in the 26-week carcinogenicity studies, the initial body weights, terminal body weights, body weight gains, food consumption, and mortality from the first 4 weeks of 26-week studies with Tg.rasH2 mice were compared with 28-day DRF studies conducted with CByB6F1 mice. Both the 26-week and the earlier respective 28-day studies were conducted with the exact same vehicle, test article, and similar dose levels. The analysis of our results further emphasizes that the EMTD and subsequent lower doses, determined on the basis of the 28-day studies in CByB6F1 mice, may not be an accurate strategy for selecting appropriate dose levels for the 26-week carcinogenicity studies in Tg.rasH2 mice. Based on the analysis presented in this article, we propose that the Tg.rasH2 mice and not the CByB6F1 mice should be used in future DRF studies. The Tg.rasH2 mice demonstrate more toxicity than the CByB6F1 mice, possibly because of their smaller size compared to CByB6F1 mice. Also, the Tg.rasH2 males appear to be more sensitive than the female Tg.rasH2 mice.

Economic evaluation study (CHEER-compliant): Cost-effectiveness analysis of RAS screening for treatment of metastatic colorectal cancer based on the CALGB 80405 trial.

PubMed

Zhou, Jing; Zhao, Rongce; Wen, Feng; Zhang, Pengfei; Tang, Ruilei; Chen, Hongdou; Zhang, Jian; Li, Qiu

2016-07-01

Cetuximab (Cetux)/Bevacizumab (Bev) treatments have shown considerably survival benefits for patients with metastatic colorectal cancer (mCRC) in the last decade. But they are costly. Currently, no data is available on the health economic implications of testing for extended RAS wild-type (wt) prior to Cetux/Bev treatments of patients with mCRC. This paper aimed to evaluate the cost-effectiveness of predictive testing for extended RAS-wt status in mCRC in the context of targeting the use of Cetux/Bev.Markov model 1 was conducted to provide evidence evaluating the cost-effectiveness of predictive testing for KRAS-wt or extended RAS-wt status based on treatments of chemotherapy plus Cetux/Bev. Markov model 2 assessed the cost-effectiveness of FOLFOX plus Cetux/Bev or FOLFIRI plus Cetux/Bev in extended RAS-wt population. Primary base case data were identified from the CALGB 80405 trial and the literatures. Costs were estimated from West China Hospital, Sichuan University, China. Survival benefits were reported in quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio (ICER) was calculated.In analysis 1, the cost per QALY was $88,394.09 for KRAS-Cetux, $80,797.82 for KRAS-Bev, $82,590.72 for RAS-Cetux, and $75,358.42 for RAS-Bev. The ICER for RAS-Cetux versus RAS-Bev was $420,700.50 per QALY gained. In analysis 2, the cost per QALY was $81,572.61, $80,856.50, $80,592.22, and $66,794.96 for FOLFOX-Cetux, FOLFOX-Bev, FOLFIRI-Cetux, and FOLFIRI-Bev, respectively. The analyses showed that the extended RAS-wt testing was less costly and more effective versus KRAS-wt testing before chemotherapy plus Cetux/Bev. Furthermore, FOLFIRI plus Bev was the most cost-effective strategy compared with others in extended RAS-wt population.It was economically favorable to identify patients with extended RAS-wt status. Furthermore, FOLFIRI plus Bev was the preferred strategy in extended RAS-wt patients.

Opposing tissue-specific roles of angiotensin in the pathogenesis of obesity, and implications for obesity-related hypertension

PubMed Central

Littlejohn, Nicole K.

2015-01-01

Metabolic disease, specifically obesity, has now become the greatest challenge to improving cardiovascular health. The renin-angiotensin system (RAS) exists as both a circulating hormone system and as a local paracrine signaling mechanism within various tissues including the brain, kidney, and adipose, and this system is strongly implicated in cardiovascular health and disease. Growing evidence also implicates the RAS in the control of energy balance, supporting the concept that the RAS may be mechanistically involved in the pathogenesis of obesity and obesity hypertension. Here, we review the involvement of the RAS in the entire spectrum of whole organism energy balance mechanisms, including behaviors (food ingestion and spontaneous physical activity) and biological processes (digestive efficiency and both aerobic and nonaerobic resting metabolic rates). We hypothesize that opposing, tissue-specific effects of the RAS to modulate these various components of energy balance can explain the apparently paradoxical results reported by energy-balance studies that involve stimulating, versus disrupting, the RAS. We propose a model in which such opposing and tissue-specific effects of the RAS can explain the failure of simple, global RAS blockade to result in weight loss in humans, and hypothesize that obesity-mediated uncoupling of endogenous metabolic rate control mechanisms can explain the phenomenon of obesity-related hypertension. PMID:26491099

Combination Use of Water Quality Modelling and Cost-Effective Analysis to Assess Environmental Benefit of a Watershed - A Case Study of Various Engineering and Management Strategy Arrangements in Taiwan

NASA Astrophysics Data System (ADS)

Fan, C.; Wu, C. Y.

2017-12-01

This study aimed to evaluate the potential environmental benefits using the water quality modelling integrated with cost-effective analysis to assess several proposed scenarios of engineering and management arrangements based on regional development planning and pollution mitigation strategy. The QUAL2Kw models of Erhjen river and its major tributary, Sanye creek, were established to simulate the river pollution indices of dissolved oxygen (DO), biochemical oxygen demand (BOD), suspended solids (SS) and ammonia nitrogen (NH3-N). The HEC-RAS was employed to calculate the hydraulic parameters and dilution impact of tidal effect in the downstream section. The verified integrated model was applied to estimating the water quality variations for several given scenarios considering the possible re-arrangement of projected pollution mitigation implementations, such as sewage system construction facilitation, additional on-site treatment facilities establishment and pig-manure anaerobic fermentation for biogas power generation in the Erhjen river watershed. As a result, the water quality of the Sanye creek was apparently improved after the completion of sewage system construction. The ammonia nitrogen concentration reduced from the level 6 to 10 times above severely-polluted standard to the merely-above level. By ignoring the impact of ammonia nitrogen on river pollution index calculation, the water quality of the lower section of the Sanye creek was improved to slightly-polluted or non-polluted level. In the scenario of anaerobic fermentation promotion, if manure anaerobic fermentation facilities were installed in all the pig farms with livestock number more than 2000, water quality was estimated to be improved slightly only. Furthermore, if all the manure waste from pig-farms is collected for subsequent electricity generation in the investigated watershed, the river pollution index is estimated to improve to moderately-polluted category for all the length of Erhjen river. Among these investigated scenarios, the one in which (1) the adjustment on sewage system scale was conducted by optimization calculation and (2) two sewage system construction was allowed at most in a year was recommended as the most cost-effective one, which increases a net present value of 2.6 billion more than the baseline.

Comparative clinical effectiveness of various 5-HT3 RA antiemetic regimens on chemotherapy-induced nausea and vomiting associated with hospital and emergency department visits in real world practice.

PubMed

Hatoum, Hind T; Lin, Swu-Jane; Buchner, Deborah; Cox, David

2012-05-01

The aim of this study was to compare the risk of chemotherapy-induced nausea and vomiting (CINV) events for various 5-HT(3) RAs in patients who received moderately (MEC) or highly emetogenic chemotherapy (HEC) by evaluating hospital or emergency department (ED) admissions. PharMetrics claims database was used to identify patients diagnosed with breast cancer (BC) who were initiated on cyclophosphamide-based adjuvant chemotherapy or with lung cancer (LC) initiated on carboplatin-based or cisplatin-based chemotherapy between 2005 and 2008. Patients were stratified in two groups: those initiated and maintained on palonosetron versus those treated with any other 5-HT(3) RA regimens in the 6-month post first chemotherapy. Risk for CINV events, identified by ICD-9-CM for nausea, vomiting, and/or dehydration, were estimated using logistic regressions, controlling for age, gender, comorbidity, and total chemotherapy doses or days. Of the 4,868 cyclophosphamide-treated BC, 5,414 carboplatin-treated LC, and 1,692 cisplatin-treated LC identified, there were 1,864 BC (38.5%), 1,806 carboplatin-treated LC (33.4%), and 390 cisplatin-treated LC (23.0%) in the palonosetron-only group. Palonosetron-only group had significantly lower probability of CINV events associated with ED/hospital admissions in all three cohorts (3.5% vs. 6.3% in BC, 9.5% vs. 13.8% in carboplatin-treated LC, and 16.4% vs. 22.6% in cisplatin-treated LC, all at p < 0.05). Logistic regressions found palonosetron-only group had significantly lower risk of CINV events (odds ratios = 0.550, 0.653, and 0.689 in BC, carboplatin-treated LC and cisplatin-treated LC, respectively, p < 0.05). Patients with lung or breast cancer receiving MEC or HEC had significantly lower risk of CINV events associated with hospital/ED admissions if initiated and maintained on palonosetron relative to patients receiving 5-HT(3) RA regimens.

K-Ras mutation detection in liquid biopsy and tumor tissue as prognostic biomarker in patients with pancreatic cancer: a systematic review with meta-analysis.

PubMed

Li, Tao; Zheng, Yuanting; Sun, Hong; Zhuang, Rongyuan; Liu, Jing; Liu, Tianshu; Cai, Weimin

2016-07-01

K-Ras gene mutations have been found in most pancreatic cancers; however, conflicting data on the prognostic value of K-Ras mutations in pancreatic cancer have been published. We conducted a meta-analysis to assess its prognostic significance. Literature searches of PubMed, EMBASE, Cochrane Library, Web of Science and Google Scholar were performed through December 2015 to identify publications exploring the association of K-Ras mutation with overall survival. Forty eligible studies involving 3427 patients with pancreatic cancer were included in the present meta-analysis. Our analysis showed a hazard ratio (HR) of negative association with survival of 1.61 [95 % confidence interval (CI) 1.36-1.90; p < 0.01] in K-Ras mutant pancreatic cancer patients. In subgroup analyses, K-Ras mutations detected in tumor tissues and in liquid biopsies had HRs of 1.37 (95 % CI 1.20-1.57; p < 0.01) and 3.16 (95 % CI 2.1-4.71; p < 0.01), respectively. In addition, the HR was higher when K-Ras mutations were detected in fresh frozen samples (HR = 2.01, 95 % CI 1.28-3.16, p = 0.002) than in formalin-fixed, paraffin-embedded (FFPE) samples (HR = 1.29, 95 % CI 1.12-1.49, p < 0.01). Though K-Ras alterations are more frequent among non-East Asian individuals than East Asian individuals, there were no significant differences in HRs of survival between the two ethnic subgroups. In conclusion, this meta-analysis suggests that K-Ras mutations are associated with a worse overall survival in pancreatic cancer patients, especially when mutations are detected in liquid biopsies or fresh frozen tumor tissue samples.

Role of the renin-angiotensin system in hepatic fibrosis and portal hypertension.

PubMed

Shim, Kwang Yong; Eom, Young Woo; Kim, Moon Young; Kang, Seong Hee; Baik, Soon Koo

2018-05-01

The renin-angiotensin system (RAS) is an important regulator of cirrhosis and portal hypertension. As hepatic fibrosis progresses, levels of the RAS components angiotensin (Ang) II, Ang-(1-7), angiotensin-converting enzyme (ACE), and Ang II type 1 receptor (AT1R) are increased. The primary effector Ang II regulates vasoconstriction, sodium homoeostasis, fibrosis, cell proliferation, and inflammation in various diseases, including liver cirrhosis, through the ACE/Ang II/AT1R axis in the classical RAS. The ACE2/Ang-(1-7)/Mas receptor and ACE2/Ang-(1-9)/AT2R axes make up the alternative RAS and promote vasodilation, antigrowth, proapoptotic, and anti-inflammatory effects; thus, countering the effects of the classical RAS axis to reduce hepatic fibrogenesis and portal hypertension. Patients with portal hypertension have been treated with RAS antagonists such as ACE inhibitors, Ang receptor blockers, and aldosterone antagonists, with very promising hemodynamic results. In this review, we examine the RAS, its roles in hepatic fibrosis and portal hypertension, and current therapeutic approaches based on the use of RAS antagonists in patients with portal hypertension.

On the Role of Specific Interactions in the Diffusion of Nanoparticles in Aqueous Polymer Solutions

PubMed Central

2013-01-01

Understanding nanoparticle diffusion within non-Newtonian biological and synthetic fluids is essential in designing novel formulations (e.g., nanomedicines for drug delivery, shampoos, lotions, coatings, paints, etc.), but is presently poorly defined. This study reports the diffusion of thiolated and PEGylated silica nanoparticles, characterized by small-angle neutron scattering, in solutions of various water-soluble polymers such as poly(acrylic acid) (PAA), poly(N-vinylpyrrolidone) (PVP), poly(ethylene oxide) (PEO), and hydroxyethylcellulose (HEC) probed using NanoSight nanoparticle tracking analysis. Results show that the diffusivity of nanoparticles is affected by their dimensions, medium viscosity, and, in particular, the specific interactions between nanoparticles and the macromolecules in solution; strong attractive interactions such as hydrogen bonding hamper diffusion. The water-soluble polymers retarded the diffusion of thiolated particles in the order PEO > PVP > PAA > HEC whereas for PEGylated silica particles retardation followed the order PAA > PVP = HEC > PEO. In the absence of specific interactions with the medium, PEGylated nanoparticles exhibit enhanced mobility compared to their thiolated counterparts despite some increase in their dimensions. PMID:24354390

On the role of specific interactions in the diffusion of nanoparticles in aqueous polymer solutions.

PubMed

Mun, Ellina A; Hannell, Claire; Rogers, Sarah E; Hole, Patrick; Williams, Adrian C; Khutoryanskiy, Vitaliy V

2014-01-14

Understanding nanoparticle diffusion within non-Newtonian biological and synthetic fluids is essential in designing novel formulations (e.g., nanomedicines for drug delivery, shampoos, lotions, coatings, paints, etc.), but is presently poorly defined. This study reports the diffusion of thiolated and PEGylated silica nanoparticles, characterized by small-angle neutron scattering, in solutions of various water-soluble polymers such as poly(acrylic acid) (PAA), poly(N-vinylpyrrolidone) (PVP), poly(ethylene oxide) (PEO), and hydroxyethylcellulose (HEC) probed using NanoSight nanoparticle tracking analysis. Results show that the diffusivity of nanoparticles is affected by their dimensions, medium viscosity, and, in particular, the specific interactions between nanoparticles and the macromolecules in solution; strong attractive interactions such as hydrogen bonding hamper diffusion. The water-soluble polymers retarded the diffusion of thiolated particles in the order PEO > PVP > PAA > HEC whereas for PEGylated silica particles retardation followed the order PAA > PVP = HEC > PEO. In the absence of specific interactions with the medium, PEGylated nanoparticles exhibit enhanced mobility compared to their thiolated counterparts despite some increase in their dimensions.

Focal adhesions and Ras are functionally and spatially integrated to mediate IL-1 activation of ERK

PubMed Central

Wang, Qin; Downey, Gregory P.; McCulloch, Christopher A.

2011-01-01

In connective tissue cells, IL-1-induced ERK activation leading to matrix metalloproteinase (MMP)-3 expression is dependent on cooperative interactions between focal adhesions and the endoplasmic reticulum (ER). As Ras can be activated on the ER, we investigated the role of Ras in IL-1 signaling and focal adhesion formation. We found that constitutively active H-Ras, K-Ras or N-Ras enhanced focal adhesion maturation and β1-integrin activation. IL-1 promoted the accumulation of Ras isoforms in ER and focal adhesion fractions, as shown in cells cotransfected with GFP-tagged Ras isoforms and YFP-ER protein and by analysis of subcellular fractions enriched for ER or focal adhesion proteins. Dominant-negative H-Ras or K-Ras reduced accumulation of H-Ras and K-Ras in focal adhesions induced by IL-1 and also blocked ERK activation and focal adhesion maturation. Ras-GRF was enriched constitutively in focal adhesion fractions and was required for Ras recruitment to focal adhesions. We conclude that Ras activation and IL-1 signaling are interactive processes that regulate the maturation of focal adhesions, which, in turn, is required for ERK activation.—Wang, Q., Downey, G. P., McCulloch, C. A. Focal adhesions and Ras are functionally and spatially integrated to mediate IL-1 activation of ERK. PMID:21719512

Effects of alkalinity on ammonia removal, carbon dioxide stripping, and system pH in semi-commercial scale water recirculating aquaculture systems operated with moving bed bioreactors

USDA-ARS?s Scientific Manuscript database

When operating water recirculating systems (RAS) with high make-up water flushing rates in locations that have low alkalinity in the raw water, such as Norway, knowledge about the required RAS alkalinity concentration is important. Flushing RAS with make-up water containing low alkalinity washes out...

A bipartite signal mediates the transfer of type IV secretion substrates of Bartonella henselae into human cells.

PubMed

Schulein, Ralf; Guye, Patrick; Rhomberg, Thomas A; Schmid, Michael C; Schröder, Gunnar; Vergunst, Annette C; Carena, Ilaria; Dehio, Christoph

2005-01-18

Bacterial type IV secretion (T4S) systems mediate the transfer of macromolecular substrates into various target cells, e.g., the conjugative transfer of DNA into bacteria or the transfer of virulence proteins into eukaryotic host cells. The T4S apparatus VirB of the vascular tumor-inducing pathogen Bartonella henselae causes subversion of human endothelial cell (HEC) function. Here we report the identification of multiple protein substrates of VirB, which, upon translocation into HEC, mediate all known VirB-dependent cellular changes. These Bartonella-translocated effector proteins (Beps) A-G are encoded together with the VirB system and the T4S coupling protein VirD4 on a Bartonella-specific pathogenicity island. The Beps display a modular architecture, suggesting an evolution by extensive domain duplication and reshuffling. The C terminus of each Bep harbors at least one copy of the Bep-intracellular delivery domain and a short positively charged tail sequence. This biparte C terminus constitutes a transfer signal that is sufficient to mediate VirB/VirD4-dependent intracellular delivery of reporter protein fusions. The Bep-intracellular delivery domain is also present in conjugative relaxases of bacterial conjugation systems. We exemplarily show that the C terminus of such a conjugative relaxase mediates protein transfer through the Bartonella henselae VirB/VirD4 system into HEC. Conjugative relaxases may thus represent the evolutionary origin of the here defined T4S signal for protein transfer into human cells.

Mutation Screening of Her-2, N-ras and Nf1 Genes in Brain Tumor Biopsies.

PubMed

Yapijakis, Christos; Adamopoulou, Maria; Tasiouka, Konstantina; Voumvourakis, Costas; Stranjalis, George

2016-09-01

A deeper understanding of the complex molecular pathology of brain malignancies is needed in order to develop more effective and targeted therapies of these highly lethal disorders. In an effort to further enlighten the molecular pathology of brain oncogenesis involving the her-2 (erbB-2/neu/ngl)/N-ras/nf1 pathway, we screened the genotypes of specimens from various types of brain tumors. The studied specimens included 35 biopsies of four general categories: 13 neuroglial tumors (4 astrocytomas, 2 oligodendrogliomas, 7 glioblastomas multiforme), 14 meningiomas, 3 other nervous system tumors (2 schwannomas, 1 craniopharyngioma) and 5 metastatic tumors (such as lung carcinomas and chronic myelocytic leukemia). Screening for most common mutations in oncogenes her-2, N-ras and tumor suppressor gene nf1 was conducted with molecular hybridization techniques (Southern blotting, dot blot and single-strand conformational polymorphism (SSCP) analysis, respectively), and was confirmed by DNA sequencing. Gene amplification of her-2 was observed in only two cases (6%), namely in one glioblastoma and in one meningioma. Screening of 3 hot spot codons of the N-ras gene (12, 13 and 61) and subsequent DNA sequencing revealed mutations in 19 biopsies encompassing all categories (54%). Screening for mutations in exons of the nf1 gene by SSCP analysis detected a novel nonsense mutation in exon 31 in a unique case of a glioblastoma biopsy (3%) taken from a patient without neurofibromatosis type I. Activated N-ras appears to be a major oncogene in brain oncogenesis, exhibiting the most important role in the her-2/N-ras/nf1 pathway. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Effects of Telephone Counseling Intervention by Pharmacists (TelCIP) on Medication Adherence; Results of a Cluster Randomized Trial

PubMed Central

Kooij, Marcel J.; Heerdink, Eibert R.; van Dijk, Liset; van Geffen, Erica C. G.; Belitser, Svetlana V.; Bouvy, Marcel L.

2016-01-01

Objectives: To assess the effect of a pharmacist telephone counseling intervention on patients' medication adherence. Design: Pragmatic cluster randomized controlled trial. Setting: 53 Community pharmacies in The Netherlands. Participants: Patients ≥18 years initiating treatment with antidepressants, bisphosphonates, Renin-Angiotensin System (RAS)-inhibitors, or statins (lipid lowering drugs). Pharmacies in arm A provided the intervention for antidepressants and bisphosphonates and usual care for RAS-inhibitors and statins. Pharmacies in arm B provided the intervention for RAS-inhibitors and statins and usual care for antidepressants and bisphosphonates. Intervention: Intervention consisted of a telephone counseling intervention 7–21 days after the start of therapy. Counseling included assessment of practical and perceptual barriers and provision of information and motivation. Main outcome measure: Primary outcome was refill adherence measured over 1 year expressed as continuous outcome and dichotomous (refill rate≥80%). Secondary outcome was discontinuation within 1 year. Results: In the control arms 3627 patients were eligible and in the intervention arms 3094 patients. Of the latter, 1054 patients (34%) received the intervention. Intention to treat analysis showed no difference in adherence rates between the intervention and the usual care arm (74.7%, SD 37.5 respectively 74.5%, 37.9). More patients starting with RAS-inhibitors had a refill ratio ≥80% in the intervention arm compared to usual care (81.4 vs. 74.9% with odds ratio (OR) 1.43, 95%CI 1.11–1.99). Comparing patients with counseling to patients with usual care (per protocol analysis), adherence was statistically significant higher for patients starting with RAS-inhibitors, statins and bisphosphonates. Patients initiating antidepressants did not benefit from the intervention. Conclusions: Telephone counseling at start of therapy improved adherence in patients initiating RAS-inhibitors. The per protocol analysis indicated an improvement for lipid lowering drugs and bisphosphonates. No effect for on adherence in patients initiating antidepressants was found. The trial was registered at www.trialregister.nl under the identifier NTR3237. PMID:27625605

Incidence and predictors of radial artery spasm during transradial coronary angiography and intervention.

PubMed

Jia, De-An; Zhou, Yu-Jie; Shi, Dong-Mei; Liu, Yu-Yang; Wang, Jian-Long; Liu, Xiao-Li; Wang, Zhi-Jian; Yang, Shi-Wei; Ge, Hai-Long; Hu, Bin; Yan, Zhen-Xian; Chen, Yi; Gao, Fei

2010-04-05

Radial artery spasm (RAS) is the most common complication in transradial coronary angiography and intervention. In this study, we designed to investigate the incidence of RAS during transradial procedures in Chinese, find out the independent predictors through multiple regression, and analyze the clinical effect of RAS during follow-up. Patients arranged to receive transradial coronary angiography and intervention were consecutively enrolled. The incidence of RAS was recorded. Univariate analysis was performed to find out the influence factors of RAS, and logistic regression analysis was performed to find out the independent predictors of RAS. The patients were asked to return 1 month later for the assessment of the radial access. The incidence of RAS was 7.8% (112/1427) in all the patients received transradial procedure. Univariate analysis indicates that young (P = 0.038), female (P = 0.026), small diameter of radial artery (P < 0.001), diabetes (P = 0.026), smoking (P = 0.019), moderate or severe pain during radial artery cannulation (P < 0.001), unsuccessful access at first attempt (P = 0.002), big sheath (P = 0.004), number of catheters (> 3) (P = 0.048), rapid baseline heart rate (P = 0.032) and long operation time (P = 0.021) were associated with RAS. Logistic regression showed that female (OR = 1.745, 95%CI: 1.148 - 3.846, P = 0.024), small radial artery diameter (OR = 4.028, 95%CI: 1.264 - 12.196, P = 0.008), diabetes (OR = 2.148, 95%CI: 1.579 - 7.458, P = 0.019) and unsuccessful access at first attempt (OR = 1.468, 95%CI: 1.212 - 2.591, P = 0.032) were independent predictors of RAS. Follow-up at (28 +/- 7) days after the procedure showed that, compared with non-spasm patients, the RAS patients had higher portion of pain (11.8% vs. 6.2%, P = 0.043). The occurrences of hematoma (7.3% vs. 5.6%, P = 0.518) and radial artery occlusion (3.6% vs. 2.6%, P = 0.534) were similar. The incidence of RAS during transradial coronary procedure was 7.8%. Logistic regression analysis showed that female, small radial artery diameter, diabetes and unsuccessful access at first attempt were the independent predictors of RAS.

ACE insertion/deletion polymorphism (rs1799752) modifies the renoprotective effect of renin-angiotensin system blockade in patients with IgA nephropathy.

PubMed

Teranishi, Junya; Yamamoto, Ryohei; Nagasawa, Yasuyuki; Shoji, Tatsuya; Iwatani, Hirotsugu; Okada, Noriyuki; Moriyama, Toshiki; Yamauchi, Atsushi; Tsubakihara, Yoshiharu; Imai, Enyu; Rakugi, Hiromi; Isaka, Yoshitaka

2015-09-01

Little is known about genetic predictors that modify the renoprotective effect of renin-angiotensin system (RAS) blockade in IgA nephropathy (IgAN). The present multicenter retrospective observational study examined effect modification between RAS blockade and three RAS-related gene polymorphisms in 237 IgAN patients, including ACE I/D (rs1799752), AT1R A1166C (rs5186) and AGT T704C (rs699). During 9.9 ± 4.2 years of observation, 63 patients progressed to a 50% increase in serum creatinine level. Only ACE I/D predicted the outcome (ACE DD vs ID/II, hazard ratio 1.86 (95% confidence interval 1.03, 3.33)) and modified the renoprotective effect of RAS blockade (p for interaction between ACE DD and RAS blockade = 0.087). RAS blockade suppressed progression in ACE DD patients but not in ID/II patients (ACE ID/II with RAS blockade as a reference; ID/II without RAS blockade 1.45 (0.72, 2.92); DD without RAS blockade 3.06 (1.39, 6.73); DD with RAS blockade 1.51 (0.54, 4.19)), which was ascertained in a model with the outcome of slope of estimated glomerular filtration rate (p = 0.045 for interaction). ACE I/D predicted the IgAN progression and the renoprotective effect of RAS blockade in IgAN patients whereas neither AT1R A1166C nor AGT T704C did. © The Author(s) 2014.

Renin-angiotensin system: an old player with novel functions in skeletal muscle.

PubMed

Cabello-Verrugio, Claudio; Morales, María Gabriela; Rivera, Juan Carlos; Cabrera, Daniel; Simon, Felipe

2015-05-01

Skeletal muscle is a tissue that shows the most plasticity in the body; it can change in response to physiological and pathological stimuli. Among the diseases that affect skeletal muscle are myopathy-associated fibrosis, insulin resistance, and muscle atrophy. A common factor in these pathologies is the participation of the renin-angiotensin system (RAS). This system can be functionally separated into the classical and nonclassical RAS axis. The main components of the classical RAS pathway are angiotensin-converting enzyme (ACE), angiotensin II (Ang-II), and Ang-II receptors (AT receptors), whereas the nonclassical axis is composed of ACE2, angiotensin 1-7 [Ang (1-7)], and the Mas receptor. Hyperactivity of the classical axis in skeletal muscle has been associated with insulin resistance, atrophy, and fibrosis. In contrast, current evidence supports the action of the nonclassical RAS as a counter-regulator axis of the classical RAS pathway in skeletal muscle. In this review, we describe the mechanisms involved in the pathological effects of the classical RAS, advances in the use of pharmacological molecules to inhibit this axis, and the beneficial effects of stimulation of the nonclassical RAS pathway on insulin resistance, atrophy, and fibrosis in skeletal muscle. © 2015 Wiley Periodicals, Inc.

3-Dimensional Root Cause Diagnosis via Co-analysis

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

Zheng, Ziming; Lan, Zhiling; Yu, Li

2012-01-01

With the growth of system size and complexity, reliability has become a major concern for large-scale systems. Upon the occurrence of failure, system administrators typically trace the events in Reliability, Availability, and Serviceability (RAS) logs for root cause diagnosis. However, RAS log only contains limited diagnosis information. Moreover, the manual processing is time-consuming, error-prone, and not scalable. To address the problem, in this paper we present an automated root cause diagnosis mechanism for large-scale HPC systems. Our mechanism examines multiple logs to provide a 3-D fine-grained root cause analysis. Here, 3-D means that our analysis will pinpoint the failure layer,more » the time, and the location of the event that causes the problem. We evaluate our mechanism by means of real logs collected from a production IBM Blue Gene/P system at Oak Ridge National Laboratory. It successfully identifies failure layer information for 219 failures during 23-month period. Furthermore, it effectively identifies the triggering events with time and location information, even when the triggering events occur hundreds of hours before the resulting failures.« less

Osteopontin Promotes Invasion, Migration and Epithelial-Mesenchymal Transition of Human Endometrial Carcinoma Cell HEC-1A Through AKT and ERK1/2 Signaling.

PubMed

Li, Yinghua; Xie, Yunpeng; Cui, Dan; Ma, Yanni; Sui, Linlin; Zhu, Chenyang; Kong, Hui; Kong, Ying

2015-01-01

Osteopontin (OPN) is an Extracellular Matrix (ECM) molecule and is involved in many physiologic and pathologic processes, including cell adhesion, angiogenesis and tumor metastasis. OPN is a well-known multifunctional factor involved in various aspects of cancer progression, including endometrial cancer. In this study, we examined the significance of OPN in endometrial cancer. The proliferation, migration and invasion ability of HEC-1A cells were detected by Cell Counting Kit-8 (CCK-8), Wound scratch assay and transwell. Western blots were employed to detect the expression of Matrix metalloproteinase-2 (MMP-2) and epithelial-mesenchymal transition (EMT)-related factors in HEC-1A cells treated with rhOPN. rhOPN promotes cell proliferation, migration and invasion in HEC-1A cells. rhOPN influenced EMT-related factors and MMP-2 expression in HEC-1A cells. rhOPN promoted HEC-1A cells migration, invasion and EMT through protein kinase B (PKB/AKT) and Extracellular regulated protein kinases (ERK1/2) signaling pathway. These results may open up a novel therapeutic strategy for endometrial cancer: namely, rhOPN have important roles in controlling growth of endometrial of cancer cells and suggest a novel target pathway for treatment of this cancer. © 2015 The Author(s) Published by S. Karger AG, Basel.

Hydrogel-based electrochemical sensor for non-invasive and continuous glucose monitoring

NASA Astrophysics Data System (ADS)

Park, Habeen; Lee, Ji-Young; Kim, Dong-Chul; Koh, Younggook; Cha, Junhoe

2017-07-01

Monitoring blood glucose level of diabetic patients is crucial in diabetes care from life threating complications. Selfmonitoring blood glucose (SMBG) that involves finger prick to draw blood samples into the measurement system is a widely-used method of routine measurement of blood glucose levels to date. SMBG includes, however, unavoidable pain problems resulting from the repetitive measurements. We hereby present a hydrogel-based electrochemical (H-EC) sensor to monitor the glucose level, non-invasively. Glucose oxidase (GOx) was immobilized in the disc-type hydroxyethyl methacrylate (HEMA) based hydrogel and kept intact in the hydrogel. Fast electron transfer mediated by Prussian blue (PB, hexacyanoferrate) generated efficient signal amplifications to facilitate the detection of the extracted glucose from the interstitial fluid. The linear response and the selectivity against glucose of the H-EC sensor were validated by chronoamperometry. For the practical use, the outcomes from the correlation of the extracted glucose concentration and the blood glucose value by on-body extraction, as well as the validation of the hydrogel-based electrochemical (H-EC) device, were applied to the on-body glucose monitoring.

Discovery of 4-aryl-N-arylcarbonyl-2-aminothiazoles as Hec1/Nek2 inhibitors. Part I: optimization of in vitro potencies and pharmacokinetic properties.

PubMed

Lee, Ying-Shuan E; Chuang, Shih-Hsien; Huang, Lynn Y L; Lai, Chun-Liang; Lin, Yu-Hsiang; Yang, Ju-Ying; Liu, Chia-Wei; Yang, Sheng-chuan; Lin, Her-Sheng; Chang, Chia-chi; Lai, Jun-Yu; Jian, Pei-Shiou; Lam, King; Chang, Jia-Ming; Lau, Johnson Y N; Huang, Jiann-Jyh

2014-05-22

A series of 4-aryl-N-arylcarbonyl-2-aminothiazoles of scaffold 4 was designed and synthesized as Hec1/Nek2 inhibitors. Structural optimization of 4 led to compound 32 bearing C-4' 4-methoxyphenoxy and 4-(o-fluoropyridyl)carbonyl groups that showed low nanomolar in vitro antiproliferative activity (IC50: 16.3-42.7 nM), high intravenous AUC (64.9 μM·h, 2.0 mg/kg) in SD rats, and significant in vivo antitumor activity (T/C = 32%, 20 mg/kg, IV) in mice bearing human MDA-MB-231 xenografts. Cell responses resulting from Hec1/Nek2 inhibition were observed in cells treated with 32, including a reduced level of Hec1 coimmunoprecipitated with Nek2, degradation of Nek2, mitotic abnormalities, and apoptosis. Compound 32 showed selectivity toward cancer cells over normal phenotype cells and was inactive in a [(3)H]astemizole competitive binding assay for hERG liability screening. Therefore, 32 is as a good lead toward the discovery of a preclinical candidate targeting Hec1/Nek2 interaction.

Role of High-End Computing in Meeting NASA's Science and Engineering Challenges

NASA Technical Reports Server (NTRS)

Biswas, Rupak

2006-01-01

High-End Computing (HEC) has always played a major role in meeting the modeling and simulation needs of various NASA missions. With NASA's newest 62 teraflops Columbia supercomputer, HEC is having an even greater impact within the Agency and beyond. Significant cutting-edge science and engineering simulations in the areas of space exploration, Shuttle operations, Earth sciences, and aeronautics research, are already occurring on Columbia, demonstrating its ability to accelerate NASA s exploration vision. The talk will describe how the integrated supercomputing production environment is being used to reduce design cycle time, accelerate scientific discovery, conduct parametric analysis of multiple scenarios, and enhance safety during the life cycle of NASA missions.

Reasoning Backwards by Design: Commentary on "Moral Reasoning among HEC Members".

PubMed

Stephens, Ashley L; Heitman, Elizabeth

2015-01-01

Empirical assessment of the practice of clinical ethics is made difficult by the limited standardization of settings, structures, processes, roles, and training for ethics consultation, as well as by whether individual ethics consultants or hospital ethics committees (HECs) provide consultation. Efforts to study the relationship between theory and practice in the work of HECs likewise require the spelling out of assumptions and definition of key variables, based in knowledge of the core concepts of clinical ethics and logistics of clinical consultation. The survey of HEC members reported by Wasserman and colleagues illustrates the difficulty of such research and calls attention to need for studies of real-time, complex decision making to inform conclusions about how theory affects practice. Copyright 2015 The Journal of Clinical Ethics. All rights reserved.

Incidence of and risk factors for newly diagnosed hyperkalemia after hospital discharge in non-dialysis-dependent CKD patients treated with RAS inhibitors.

PubMed

Saito, Yuki; Yamamoto, Hiroyuki; Nakajima, Hideki; Takahashi, Osamu; Komatsu, Yasuhiro

2017-01-01

Renin-angiotensin system (RAS) inhibitors have been increasingly prescribed due to their beneficial effects on end-organ protection. Iatrogenic hyperkalemia is a well-known life-threatening complication of RAS inhibitor use in chronic kidney disease (CKD) patients. We hypothesized that CKD patients treated with RAS inhibitors frequently develop hyperkalemia after hospital discharge even if they were normokalemic during their hospitalization because their lifestyles change substantially after discharge. The present study aimed to examine the incidence of newly diagnosed hyperkalemia, the timing of hyperkalemia, and its risk factors in CKD patients treated with RAS inhibitors at the time of hospital discharge. We retrospectively enrolled patients aged 20 years or older with CKD G3-5 (estimated glomerular filtration rate < 60 mL/min/1.73 m2) and who were treated with RAS inhibitors and discharged from St. Luke's International Hospital between July 2011 and December 2015. Patients who were under maintenance dialysis or had hyperkalemic events before discharge were excluded. Data regarding the patients' age, sex, CKD stage, diabetes mellitus status, malignancy status, combined use of RAS inhibitors, concurrent medication, and hyperkalemic events after discharge were extracted from the hospital database. Our primary outcome was hyperkalemia, defined as serum potassium ≥ 5.5 mEq/L. Multiple logistic regression and Kaplan-Meier analyses were performed to identify the risk factors for and the timing of hyperkalemia, respectively. Among the 986 patients, 121 (12.3%) developed hyperkalemia after discharge. In the regression analysis, relative to CKD G3a, G3b [odds ratio (OR): 1.88, 95% confidence interval 1.20-2.97] and G4-5 (OR: 3.40, 1.99-5.81) were significantly associated with hyperkalemia. The use of RAS inhibitor combinations (OR: 1.92, 1.19-3.10), malignancy status (OR: 2.10, 1.14-3.86), and baseline serum potassium (OR: 1.91, 1.23-2.97) were also significantly associated with hyperkalemia. The Kaplan-Meier analysis showed that hyperkalemia was most frequent during the early period after discharge, particularly within one month. Hyperkalemia was frequent during the early period after discharge among previously normokalemic CKD patients who were treated with RAS inhibitors. Appropriate follow-up after discharge should be required for these patients, particularly those with advanced CKD or malignancy status, such as hematological malignancy or late-stage malignancy, and those who are treated with multiple RAS inhibitors.

Incidence of and risk factors for newly diagnosed hyperkalemia after hospital discharge in non-dialysis-dependent CKD patients treated with RAS inhibitors

PubMed Central

Saito, Yuki; Nakajima, Hideki; Takahashi, Osamu; Komatsu, Yasuhiro

2017-01-01

Introduction Renin-angiotensin system (RAS) inhibitors have been increasingly prescribed due to their beneficial effects on end-organ protection. Iatrogenic hyperkalemia is a well-known life-threatening complication of RAS inhibitor use in chronic kidney disease (CKD) patients. We hypothesized that CKD patients treated with RAS inhibitors frequently develop hyperkalemia after hospital discharge even if they were normokalemic during their hospitalization because their lifestyles change substantially after discharge. The present study aimed to examine the incidence of newly diagnosed hyperkalemia, the timing of hyperkalemia, and its risk factors in CKD patients treated with RAS inhibitors at the time of hospital discharge. Methods We retrospectively enrolled patients aged 20 years or older with CKD G3-5 (estimated glomerular filtration rate < 60 mL/min/1.73 m2) and who were treated with RAS inhibitors and discharged from St. Luke’s International Hospital between July 2011 and December 2015. Patients who were under maintenance dialysis or had hyperkalemic events before discharge were excluded. Data regarding the patients’ age, sex, CKD stage, diabetes mellitus status, malignancy status, combined use of RAS inhibitors, concurrent medication, and hyperkalemic events after discharge were extracted from the hospital database. Our primary outcome was hyperkalemia, defined as serum potassium ≥ 5.5 mEq/L. Multiple logistic regression and Kaplan-Meier analyses were performed to identify the risk factors for and the timing of hyperkalemia, respectively. Results Among the 986 patients, 121 (12.3%) developed hyperkalemia after discharge. In the regression analysis, relative to CKD G3a, G3b [odds ratio (OR): 1.88, 95% confidence interval 1.20–2.97] and G4-5 (OR: 3.40, 1.99–5.81) were significantly associated with hyperkalemia. The use of RAS inhibitor combinations (OR: 1.92, 1.19–3.10), malignancy status (OR: 2.10, 1.14–3.86), and baseline serum potassium (OR: 1.91, 1.23–2.97) were also significantly associated with hyperkalemia. The Kaplan-Meier analysis showed that hyperkalemia was most frequent during the early period after discharge, particularly within one month. Conclusion Hyperkalemia was frequent during the early period after discharge among previously normokalemic CKD patients who were treated with RAS inhibitors. Appropriate follow-up after discharge should be required for these patients, particularly those with advanced CKD or malignancy status, such as hematological malignancy or late-stage malignancy, and those who are treated with multiple RAS inhibitors. PMID:28877239

Mitigation of Remedial Action Schemes by Decentralized Robust Governor Control

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

Elizondo, Marcelo A.; Marinovici, Laurentiu D.; Lian, Jianming

This paper presents transient stability improvement by a new distributed hierarchical control architecture (DHC). The integration of remedial action schemes (RAS) to the distributed hierarchical control architecture is studied. RAS in power systems are designed to maintain stability and avoid undesired system conditions by rapidly switching equipment and/or changing operating points according to predetermined rules. The acceleration trend relay currently in use in the US western interconnection is an example of RAS that trips generators to maintain transient stability. The link between RAS and DHC is through fast acting robust turbine/governor control that can also improve transient stability. In thismore » paper, the influence of the decentralized robust turbine/governor control on the design of RAS is studied. Benefits of combining these two schemes are increasing power transfer capability and mitigation of RAS generator tripping actions; the later benefit is shown through simulations.« less

Galectin-1 dimers can scaffold Raf-effectors to increase H-ras nanoclustering

PubMed Central

Blaževitš, Olga; Mideksa, Yonatan G.; Šolman, Maja; Ligabue, Alessio; Ariotti, Nicholas; Nakhaeizadeh, Hossein; Fansa, Eyad K.; Papageorgiou, Anastassios C.; Wittinghofer, Alfred; Ahmadian, Mohammad R.; Abankwa, Daniel

2016-01-01

Galectin-1 (Gal-1) dimers crosslink carbohydrates on cell surface receptors. Carbohydrate-derived inhibitors have been developed for cancer treatment. Intracellularly, Gal-1 was suggested to interact with the farnesylated C-terminus of Ras thus specifically stabilizing GTP-H-ras nanoscale signalling hubs in the membrane, termed nanoclusters. The latter activity may present an alternative mechanism for how overexpressed Gal-1 stimulates tumourigenesis. Here we revise the current model for the interaction of Gal-1 with H-ras. We show that it indirectly forms a complex with GTP-H-ras via a high-affinity interaction with the Ras binding domain (RBD) of Ras effectors. A computationally generated model of the Gal-1/C-Raf-RBD complex is validated by mutational analysis. Both cellular FRET as well as proximity ligation assay experiments confirm interaction of Gal-1 with Raf proteins in mammalian cells. Consistently, interference with H-rasG12V-effector interactions basically abolishes H-ras nanoclustering. In addition, an intact dimer interface of Gal-1 is required for it to positively regulate H-rasG12V nanoclustering, but negatively K-rasG12V nanoclustering. Our findings suggest stacked dimers of H-ras, Raf and Gal-1 as building blocks of GTP-H-ras-nanocluster at high Gal-1 levels. Based on our results the Gal-1/effector interface represents a potential drug target site in diseases with aberrant Ras signalling. PMID:27087647

A Self-Powered Thin-Film Radiation Detector Using Intrinsic High-Energy Current (HEC) (Author’s Final Version)

DTIC Science & Technology

2016-09-08

10.1118/1.4935531. A new radiation detection method relies on high-energy current (HEC) formed by secondary charged particles in the detector material...photocurrent, radiation detection , self-powered, thin-film U U U SAR 17 Dr. Joseph Wander Reset A Self-powered thin-film radiation detector using intrinsic...Program, Lowell, MA 01854 Purpose: We introduce a radiation detection method that relies on high-energy current (HEC) formed by secondary 10 charged

Loss of Life, Evacuation and Emergency Management: Comparison and Application to Case Studies in the USA

DTIC Science & Technology

2013-01-22

eK ay a nd M cC le lla nd G ra ha m Katrina HEC -FIA LifeSim Figure 1: Comparison of loss of life models (based on Johnstone et al., 2005...Katrina HEC FIA Lifesim Application: flood types Levee breaching, river , coastal Levee breaching, river , coastal levee breaching, dam failure...Mortality – Overtopping with breach Center Side of American River (OTSC) Figure 31: Mortality for the HEC -FIA method for the two

Genetic analysis of Ras genes in epidermal development and tumorigenesis

PubMed Central

Drosten, Matthias; Lechuga, Carmen G; Barbacid, Mariano

2013-01-01

Proliferation and differentiation of epidermal keratinocytes are tightly controlled to ensure proper development and homeostasis of the epidermis. The Ras family of small GTPases has emerged as a central node in the coordination of cell proliferation in the epidermis. Recent genetic evidence from mouse models has revealed that the intensity of Ras signaling modulates the proliferative capacity of epidermal keratinocytes. Interfering with Ras signaling either by combined elimination of the 3 Ras genes from the basal layer of the epidermis or by overexpression of dominant-negative Ras isoforms caused epidermal thinning due to hypoproliferation of keratinocytes. In contrast, overexpression of oncogenic Ras mutants in different epidermal cell layers led to hyperproliferative phenotypes including the development of papillomas and squamous cell carcinomas. Here, we discuss the value of loss- and gain-of-function studies in mouse models to assess the role of Ras signaling in the control of epidermal proliferation. PMID:24150175

Integration of rainfall/runoff and geomorphological analyses flood hazard in small catchments: case studies from the southern Apennines (Italy)

NASA Astrophysics Data System (ADS)

Palumbo, Manuela; Ascione, Alessandra; Santangelo, Nicoletta; Santo, Antonio

2017-04-01

We present the first results of an analysis of flood hazard in ungauged mountain catchments that are associated with intensely urbanized alluvial fans. Assessment of hydrological hazard has been based on the integration of rainfall/runoff modelling of drainage basins with geomorphological analysis and mapping. Some small and steep, ungauged mountain catchments located in various areas of the southern Apennines, in southern Italy, have been chosen as test sites. In the last centuries, the selected basins have been subject to heavy and intense precipitation events, which have caused flash floods with serious damages in the correlated alluvial fan areas. Available spatial information (regional technical maps, DEMs, land use maps, geological/lithological maps, orthophotos) and an automated GIS-based procedure (ArcGis tools and ArcHydro tools) have been used to extract morphological, hydrological and hydraulic parameters. Such parameters have been used to run the HEC (Hydrologic Engineering Center of the US Army Corps of Engineers) software (GeoHMS, GeoRAS, HMS and RAS) based on rainfall-runoff models, which have allowed the hydrological and hydraulic simulations. As the floods occurred in the studied catchments have been debris flows dominated, the solid load simulation has been also performed. In order to validate the simulations, we have compared results of the modelling with the effects produced by past floods. Such effects have been quantified through estimations of both the sediment volumes within each catchment that have the potential to be mobilised (pre-event) during a sediment transfer event, and the volume of sediments delivered by the debris flows at basins' outlets (post-event). The post-event sediment volume has been quantified through post-event surveys and Lidar data. Evaluation of the pre-event sediment volumes in single catchments has been based on mapping of sediment storages that may constitute source zones of bed load transport and debris flows. For such an approach has been used a methodology that consists of the application of a process-based geomorphological mapping, based on data derived from GIS analysis using high-resolution DEMs, field measurements and aerial photograph interpretations. Our integrated approach, which allows quantification of the flow rate and a semi-quantitative assessment of sediment that can be mobilized during hydro-meteorological events, is applied for the first time to torrential catchmenmts of the southern Apennines and may significantly contribute to previsional studies aimed at risk mitigation in the study region.

Optimizing depuration of salmon in RAS

USDA-ARS?s Scientific Manuscript database

Fish cultured within water recirculating aquaculture systems (RAS) can acquire "earthy" or "musty" off-flavors due to bioaccumulation of the compounds geosmin and 2-methylisoborneol (MIB), respectively, which are produced by certain bacterial species present in RAS biosolids and microbial biofilms. ...

RAS mutation prevalence among patients with metastatic colorectal cancer: a meta-analysis of real-world data.

PubMed

Kafatos, George; Niepel, Daniela; Lowe, Kimberley; Jenkins-Anderson, Sophie; Westhead, Hal; Garawin, Tamer; Traugottová, Zuzana; Bilalis, Antonios; Molnar, Edit; Timar, Jozsef; Toth, Erika; Gouvas, Nikolaos; Papaxoinis, George; Murray, Samuel; Mokhtar, Nadia; Vosmikova, Hana; Fabian, Pavel; Skalova, Alena; Wójcik, Piotr; Tysarowski, Andrzej; Barugel, Mario; van Krieken, J Han; Trojan, Jörg

2017-07-27

A confirmed wild-type RAS tumor status is commonly required for prescribing anti-EGFR treatment for metastatic colorectal cancer. This noninterventional, observational research project estimated RAS mutation prevalence from real-world sources. Aggregate RAS mutation data were collected from 12 sources in three regions. Each source was analyzed separately; pooled prevalence estimates were then derived from meta-analyses. The pooled RAS mutation prevalence from 4431 tumor samples tested for RAS mutation status was estimated to be 43.6% (95% CI: 38.8-48.5%); ranging from 33.7% (95% CI: 28.4-39.3%) to 54.1% (95% CI: 51.7-56.5%) between sources. The RAS mutation prevalence estimates varied among sources. The reasons for this are not clear and highlight the need for further research.

Model-Aided Altimeter-Based Water Level Forecasting System in Mekong River

NASA Astrophysics Data System (ADS)

Chang, C. H.; Lee, H.; Hossain, F.; Okeowo, M. A.; Basnayake, S. B.; Jayasinghe, S.; Saah, D. S.; Anderson, E.; Hwang, E.

2017-12-01

Mekong River, one of the massive river systems in the world, has drainage area of about 795,000 km2 covering six countries. People living in its drainage area highly rely on resources given by the river in terms of agriculture, fishery, and hydropower. Monitoring and forecasting the water level in a timely manner, is urgently needed over the Mekong River. Recently, using TOPEX/Poseidon (T/P) altimetry water level measurements in India, Biancamaria et al. [2011] has demonstrated the capability of an altimeter-based flood forecasting system in Bangladesh, with RMSE from 0.6 - 0.8 m for lead times up to 5 days on 10-day basis due to T/P's repeat period. Hossain et al. [2013] further established a daily water level forecasting system in Bangladesh using observations from Jason-2 in India and HEC-RAS hydraulic model, with RMSE from 0.5 - 1.5 m and an underestimating mean bias of 0.25 - 1.25 m. However, such daily forecasting system relies on a collection of Jason-2 virtual stations (VSs) to ensure frequent sampling and data availability. Since the Mekong River is a meridional river with few number of VSs, the direct application of this system to the Mekong River becomes challenging. To address this problem, we propose a model-aided altimeter-based forecasting system. The discharge output by Variable Infiltration Capacity hydrologic model is used to reconstruct a daily water level product at upstream Jason-2 VSs based on the discharge-to-level rating curve. The reconstructed daily water level is then used to perform regression analysis with downstream in-situ water level to build regression models, which are used to forecast a daily water level. In the middle reach of the Mekong River from Nakhon Phanom to Kratie, a 3-day lead time forecasting can reach RMSE about 0.7 - 1.3 m with correlation coefficient around 0.95. For the lower reach of the Mekong River, the water flow becomes more complicated due to the reversal flow between the Tonle Sap Lake and the Mekong River, while ocean tide can also propagate into this region. By considering the influence of Tonle Sap Lake and the Mekong River through multi-variable regression analysis, the forecasting results from Prek Kdam to Chau Doc/Tan Chau reach RMSE from about 0.3 - 0.65 m and correlation coefficient about 0.93- 0.97 with 5-day lead time.

Lysophosphatidic acid (LPA) effects on endometrial carcinoma in vitro proliferation, invasion, and matrix metalloproteinase activity.

PubMed

Wang, Feng-qiang; Ariztia, Edgardo V; Boyd, Leslie R; Horton, Faith R; Smicun, Yoel; Hetherington, Jessica A; Smith, Phillip J; Fishman, David A

2010-04-01

Lysophosphatidic acid (LPA) has potent growth-regulatory effect in many cell types and has been linked to the in vivo tumor growth and metastasis in several malignancies. The goal of this study was to assess the regulation of (EC) microenvironment by LPA through the examination of its effect on cell proliferation, migration, invasion, uPA activity, and matrix metalloproteinase (MMP) secretion/activation. All experiments were performed in vitro using an EC cell line, HEC-1A. Cell proliferation was determined using the Promega MTS proliferation assay following 48 h of exposures to different concentrations of LPA (0.1, 1.0 and 10.0 microM). Cell invasion was assessed using a modified Boyden chamber assay with collagen I coated on the membrane. HEC-1A motility was examined by Boyden chamber migration assay as well as the scratch wound closure assay on type I collagen. MMP secretion/activation in HEC-1A conditioned medium was detected by gelatin zymography. MMP-7 mRNA expression was determined using real-time PCR. uPA activity was measured using a coupled colorimetric assay. LPA, at the concentrations of 0.1 and 1.0 microM, significantly induced the proliferation of HEC-1A cells (p<0.01). At 10 microM, LPA- induced HEC-1A proliferation to a less extent and showed no significant effect on HEC-1A invasion and migration (p>0.05). Gelatin zymogram showed that HEC-1A cells secreted high levels of MMP-7, while MMP-2 and MMP-9 are barely detectable. In addition, LPA significantly enhanced uPA activity in HEC-1A conditioned medium in a concentration-dependent manner. LPA is a potent modulator of cellular proliferation and invasion for EC cells. It also has the capacity to stimulate the secretion/activity of uPA and MMP-7. Those results suggest that LPA is a bioactive modulator of EC microenvironment and may have a distinct regulation mechanism as observed in epithelial ovarian cancer. Copyright 2009. Published by Elsevier Inc.

Nitrative and oxidative DNA damage caused by K-ras mutation in mice

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

Ohnishi, Shiho; Saito, Hiromitsu; Suzuki, Noboru

2011-09-23

Highlights: {yields} Mutated K-ras in transgenic mice caused nitrative DNA damage, 8-nitroguanine. {yields} The mutagenic 8-nitroguanine seemed to be generated by iNOS via Ras-MAPK signal. {yields} Mutated K-ras produces additional mutagenic lesions, as a new oncogenic role. -- Abstract: Ras mutation is important for carcinogenesis. Carcinogenesis consists of multi-step process with mutations in several genes. We investigated the role of DNA damage in carcinogenesis initiated by K-ras mutation, using conditional transgenic mice. Immunohistochemical analysis revealed that mutagenic 8-nitroguanine and 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG) were apparently formed in adenocarcinoma caused by mutated K-ras. 8-Nitroguanine was co-localized with iNOS, eNOS, NF-{kappa}B, IKK, MAPK, MEK,more » and mutated K-ras, suggesting that oncogenic K-ras causes additional DNA damage via signaling pathway involving these molecules. It is noteworthy that K-ras mutation mediates not only cell over-proliferation but also the accumulation of mutagenic DNA lesions, leading to carcinogenesis.« less

Extent of areal inundation of riverine wetlands along five river systems in the upper Hillsborough river watershed, west-central Florida

USGS Publications Warehouse

Lewelling, B.R.

2004-01-01

Riverine and palustrine wetlands are a major ecological component of river basins in west-central Florida. Healthy wetlands are dependent, in part, upon the frequency and duration of periodic flooding or inundation. This report assesses the extent, area, depth, frequency, and duration of periodic flooding and the effects of potential surface-water withdrawals on wetlands along five river systems in the upper Hillsborough River watershed: Hillsborough and New Rivers, Blackwater and Itchepackesassa Creeks, and East Canal. Results of the study were derived from step-backwater analyses performed for each of the river systems using the U.S. Army Corps of Engineers Hydrologic Engineering Center-River Analysis System (HEC-RAS) one-dimensional model. Step-backwater analyses were performed based on daily mean discharges at the 10th, 50th, 70th, 80th, 90th, 95th, 99.5th, and 99.97th percentiles for selected periods. The step-backwater analyses computed extent of inundation, area of inundation, and hydraulic depth. An assessment of the net reduction of areal inundation for each of the selected percentile discharges was computed if 10 percent of the total river flow were diverted for potential withdrawals. The extent of areal inundation at a cross section is controlled by discharge volume, topography, and the degree to which the channel is incised. Areal inundation can occur in reaches characterized by low topographic relief in the upper Hillsborough watershed during most, if not all, selected discharge percentiles. Most river systems in the watershed, however, have well defined and moderately incised channels that generally confine discharges within the banks at the 90th percentile. The greatest increase in inundated area along the five river systems generally occurred between the 95th to 99.5th percentile discharges. The decrease in inundated area that would result from a potential 10-percent discharge withdrawal at the five river systems ranged as follows: Hillsborough River, 7 to 940 acres (2.0 to 6.0 percent); and New River, 0.2 to 58.9 acres (0 to 11.9 percent); Blackwater Creek, 3.3 to 148 acres (2.2 to 9.4 percent); Itchepackesassa Creek, 1.0 to 104 acres (0.9 to 10.8 percent); and East Canal 0.7 to 34.6 acres (0.5 to 7.6 percent).

Physicochemical properties of pH-sensitive hydrogels based on hydroxyethyl cellulose-hyaluronic acid and for applications as transdermal delivery systems for skin lesions.

PubMed

Kwon, Soon Sik; Kong, Bong Ju; Park, Soo Nam

2015-05-01

We investigated the physicochemical properties of pH-sensitive hydroxyethyl cellulose (HEC)/hyaluronic acid (HA) complex hydrogels containing isoliquiritigenin (ILTG), and discussed potential applications as transdermal delivery systems for the treatment of skin lesions caused by pH imbalance. HA has skin compatibility and pH functional groups and HEC serves as scaffold to build hydrogels with varied HCE:HA mass ratio. Hydrogels were synthesized via chemical cross-linking, and three-dimensional network structures were characterized via scanning electron microscopy (SEM). The swelling properties and polymer ratios of the hydrogels were investigated at pH values in the range 1-13. HECHA13 (i.e., an HEC:HA mass ratio of 1:3) was found to have optimal rheological and adhesive properties, and was used to investigate the drug release efficiency as a function of pH; the efficiency was greater than 70% at pH 7. Antimicrobial activity assays against Propionibacterium acnes were conducted to take advantage of the pH-sensitive properties of HECHA13. At pH 7, we found that HECHA13, which contained ILTG, inhibited the growth of P. acnes. Furthermore, HECHA13 was found to exhibit excellent permeability into the skin, which penetrated mostly via the hair follicle. These results indicate that this pH-sensitive hydrogel is effective as a transdermal delivery system for antimicrobial therapeutics, with potential applications in the treatment of acne. Copyright © 2015 Elsevier B.V. All rights reserved.

Psychometric properties of the Persian version of the “Hospital Ethical Climate Survey”

PubMed Central

Khalesi, Nader; Arabloo, Jalal; Khosravizadeh, Omid; Taghizadeh, Sanaz; Heyrani, Ali; Ebrahimian, Abbasali

2014-01-01

In order to improve the ethical climate in health care organizations, it is important to apply a valid measure. This study aimed to investigate the psychometric properties of the Persian version of the Hospital Ethical Climate Survey (HECS) and to assess nurses’ perceptions of the ethical climate in teaching hospitals of Iran. A cross-sectional study of randomly selected nurses (n = 187) was conducted in three teaching general hospitals of Tehran, capital of Iran. Olson’s Hospital Ethical Climate Survey (HECS), a self-administered questionnaire, was used to assess the nurses’ perceptions of the hospital ethical climate. Descriptive statistics, confirmatory factor analysis (CFA), internal consistency, and correlation were used to analyze the data. CFA showed acceptable model fit: an standardized root mean square residual (SRMR) of 0.064, an non-normalized fit index (NNFI) of 0.96, a comparative fit index (CFI) of 0.96, and an root mean square error of approximation (RMSEA) of 0.075. The Cronbach’s alpha values were acceptable and ranging from 0.69 to 0.85. The overall Cronbach’s alpha coefficient was 0.94. The factor loadings for all ethical climate items were between 0.50 and 0.80, which revealed good structure of the Persian version of the HECS. Survey findings showed that the “managers” subscale had the highest score and the subscale of “doctors” had the lowest score. This study shows that the Persian version of the HECS is a valid and reliable instrument for measuring nurses’ perceptions of the ethical climate in hospitals of Iran PMID:25512834

Influences of neutralization of superabsorbent hydrogel from hydroxyethyl cellulose on water swelling capacities

NASA Astrophysics Data System (ADS)

Adair, Ajaman; Klinpituksa, Pairote; Kaesaman, Azizon

2017-08-01

In this research, superabsorbent hydrogels were synthesized by graft copolymerization of hydroxyethyl cellulose (HEC) and polyacrylamide (PAM) under the initiation of potassium persulfate (KPS). The polymer networks were constructed using N,N'-methylenebisacrylamide (MBA), and the reaction was performed in an aqueous solution. The extent of grafting products was evaluated form grafting efficiency (%GE) and percentage of add-ons at HEC/AM ratios of 1: 10. The water swelling capacities, in terms of swelling capacity and weight loss, of resultant superabsorbent polymers (SAPs) after solvent extraction were determined for swelling behaviors. The result showed that the SAP had poor water absorption of approximately up to 23 g/g. To enhance swelling capacity of SAPs, an alkaline hydrolysis was done by using two types of alkaline bases, i.e., 2 M NaOH and 2 M KOH solution. The obtained treatment SAPs were neutralized by washing with distilled water and 0.5 M HCl until the liquors pH was nearly 7. They were found that the treatment SAPs showed the highest water absorption up to 317 g/g. Influences of various fluids pH values ranging between 4 and 10, on water swelling capacities of SAPs were also investigated. Under optimal pH value, the highest water absorptions of SAP was 382 g/g. To confirm the grafting reaction of PAM onto HEC backbone, FT-IR analysis was used. The results revealed absorption bands of the HEC backbone and new absorption bands from the grafted copolymer. Furthermore, the FT-IR spectrum was proved that washing with distilled water can alter the chemical functional group of SAPs.

A bipartite signal mediates the transfer of type IV secretion substrates of Bartonella henselae into human cells

PubMed Central

Schulein, Ralf; Guye, Patrick; Rhomberg, Thomas A.; Schmid, Michael C.; Schröder, Gunnar; Vergunst, Annette C.; Carena, Ilaria; Dehio, Christoph

2005-01-01

Bacterial type IV secretion (T4S) systems mediate the transfer of macromolecular substrates into various target cells, e.g., the conjugative transfer of DNA into bacteria or the transfer of virulence proteins into eukaryotic host cells. The T4S apparatus VirB of the vascular tumor-inducing pathogen Bartonella henselae causes subversion of human endothelial cell (HEC) function. Here we report the identification of multiple protein substrates of VirB, which, upon translocation into HEC, mediate all known VirB-dependent cellular changes. These Bartonella-translocated effector proteins (Beps) A-G are encoded together with the VirB system and the T4S coupling protein VirD4 on a Bartonella-specific pathogenicity island. The Beps display a modular architecture, suggesting an evolution by extensive domain duplication and reshuffling. The C terminus of each Bep harbors at least one copy of the Bep-intracellular delivery domain and a short positively charged tail sequence. This biparte C terminus constitutes a transfer signal that is sufficient to mediate VirB/VirD4-dependent intracellular delivery of reporter protein fusions. The Bep-intracellular delivery domain is also present in conjugative relaxases of bacterial conjugation systems. We exemplarily show that the C terminus of such a conjugative relaxase mediates protein transfer through the Bartonella henselae VirB/VirD4 system into HEC. Conjugative relaxases may thus represent the evolutionary origin of the here defined T4S signal for protein transfer into human cells. PMID:15642951

Enhancement of Th1 immune responses to recombinant influenza nucleoprotein by Ribi adjuvant.

PubMed

Cargnelutti, Diego E; Sanchez, María A V; Alvarez, Paula; Boado, Lorena; Mattion, Nora; Scodeller, Eduardo A

2013-04-01

A broad coverage influenza vaccine against multiple viral strains based on the viral nucleoprotein (NP) is a goal pursued by many laboratories. If the goal is to formulate the vaccine with recombinant NP it is essential to count on adjuvants capable of inducing cellular immunity. This work have studied the effect of the monophosphoryl lipid A and trehalose dimycolate, known as the Ribi Adjuvant System (RAS), in the immune response induced in mice immunized with recombinant NP. The NP was formulated with RAS and used to immunize BALB/c mice. Immunizations with NP-RAS increased the humoral and cellular immune responses compared to unadjuvanted NP. The predominant antibody isotype was IgG2a, suggesting the development of a Th1 response. Analysis of the cytokines from mice immunized with NP-RAS showed a significant increase in the production of IFN-g and a decreased production of IL-10 and IL-4 compared to controls without RAS. These results are similar to those usually obtained using Freund’s adjuvant, known to induce Th1 and CTL responses when co-administered with purified proteins, and suggest that a similar approach may be possible to enhance the performance of a T-cell vaccine containing NP.

Effect of Angiotensin II and Small GTPase Ras Signaling Pathway Inhibition on Early Renal Changes in a Murine Model of Obstructive Nephropathy

PubMed Central

Rodríguez-Peña, Ana B.; Fuentes-Calvo, Isabel; Docherty, Neil G.; Arévalo, Miguel; Grande, María T.; Eleno, Nélida; Pérez-Barriocanal, Fernando; López-Novoa, José M.

2014-01-01

Tubulointerstitial fibrosis is a major feature of chronic kidney disease. Unilateral ureteral obstruction (UUO) in rodents leads to the development of renal tubulointerstitial fibrosis consistent with histopathological changes observed in advanced chronic kidney disease in humans. The purpose of this study was to assess the effect of inhibiting angiotensin II receptors or Ras activation on early renal fibrotic changes induced by UUO. Animals either received angiotensin II or underwent UUO. UUO animals received either losartan, atorvastatin, and farnesyl transferase inhibitor (FTI) L-744,832, or chaetomellic acid A (ChA). Levels of activated Ras, phospho-ERK1/2, phospho-Akt, fibronectin, and α-smooth muscle actin were subsequently quantified in renal tissue by ELISA, Western blot, and/or immunohistochemistry. Our results demonstrate that administration of angiotensin II induces activation of the small GTPase Ras/Erk/Akt signaling system, suggesting an involvement of angiotensin II in the early obstruction-induced activation of renal Ras. Furthermore, upstream inhibition of Ras signalling by blocking either angiotensin AT1 type receptor or by inhibiting Ras prenylation (atorvastatin, FTI o ChA) reduced the activation of the Ras/Erk/Akt signaling system and decreased the early fibrotic response in the obstructed kidney. This study points out that pharmacological inhibition of Ras activation may hold promise as a future strategy in the prevention of renal fibrosis. PMID:25101263

Effect of angiotensin II and small GTPase Ras signaling pathway inhibition on early renal changes in a murine model of obstructive nephropathy.

PubMed

Rodríguez-Peña, Ana B; Fuentes-Calvo, Isabel; Docherty, Neil G; Arévalo, Miguel; Grande, María T; Eleno, Nélida; Pérez-Barriocanal, Fernando; López-Novoa, José M

2014-01-01

Tubulointerstitial fibrosis is a major feature of chronic kidney disease. Unilateral ureteral obstruction (UUO) in rodents leads to the development of renal tubulointerstitial fibrosis consistent with histopathological changes observed in advanced chronic kidney disease in humans. The purpose of this study was to assess the effect of inhibiting angiotensin II receptors or Ras activation on early renal fibrotic changes induced by UUO. Animals either received angiotensin II or underwent UUO. UUO animals received either losartan, atorvastatin, and farnesyl transferase inhibitor (FTI) L-744,832, or chaetomellic acid A (ChA). Levels of activated Ras, phospho-ERK1/2, phospho-Akt, fibronectin, and α-smooth muscle actin were subsequently quantified in renal tissue by ELISA, Western blot, and/or immunohistochemistry. Our results demonstrate that administration of angiotensin II induces activation of the small GTPase Ras/Erk/Akt signaling system, suggesting an involvement of angiotensin II in the early obstruction-induced activation of renal Ras. Furthermore, upstream inhibition of Ras signalling by blocking either angiotensin AT1 type receptor or by inhibiting Ras prenylation (atorvastatin, FTI o ChA) reduced the activation of the Ras/Erk/Akt signaling system and decreased the early fibrotic response in the obstructed kidney. This study points out that pharmacological inhibition of Ras activation may hold promise as a future strategy in the prevention of renal fibrosis.

The effect of renin-angiotensin system blockade on renal protection in chronic kidney disease patients with hyperkalemia.

PubMed

Lee, Ju-Hyun; Kwon, Young Eun; Park, Jung Tak; Lee, Mi Jung; Oh, Hyung Jung; Han, Seung Hyeok; Kang, Shin-Wook; Choi, Kyu Hun; Yoo, Tae-Hyun

2014-12-01

The aim of this study was to determine the effects of renin-angiotensin system (RAS) blockade maintenance on renal protection in chronic kidney disease (CKD) patients with hyperkalemia occurring during treatment with RAS blockade. CKD III or IV patients, who were prescribed with RAS blockers and also had hyperkalemia, were included. The study population was divided into two groups based on maintenance or withdrawal of RAS blocker. Renal outcomes (doubling of creatinine or end-stage renal disease) and incidence of hyperkalemia were compared between the two groups. Out of 258 subjects who developed hyperkalemia during treatment with RAS blockers, 150 (58.1%) patients continued on RAS blockades, while RAS blockades were discontinued for more than 3 months in the remaining 108 patients. Renal event-free survival was significantly higher in the maintenance group compared with the withdrawal group. Cox proportional hazard ratio for renal outcomes was 1.35 (95% CI: 1.08-1.92, p=0.04) in the withdrawal group compared with the maintenance group. However, the incidence of hyperkalemia and hyperkalemia-related hospitalization or mortality did not differ between the two groups. This study demonstrated that the maintenance of RAS blockade is beneficial for the preservation of renal function and relatively tolerable in patients with CKD and hyperkalemia occurring during treatment with RAS blockade. © The Author(s) 2014.

Structure of the c-Ki-ras gene in a rat fibrosarcoma induced by 1,8-dinitropyrene.

PubMed Central

Tahira, T; Hayashi, K; Ochiai, M; Tsuchida, N; Nagao, M; Sugimura, T

1986-01-01

Restriction enzyme maps were made of the region around exons 1 and 2 of activated c-Ki-ras of a fibrosarcoma (1,8-DNP2) induced in a rat by 1,8-dinitropyrene. Nucleotide sequence analysis revealed that activated c-Ki-ras shows a G----T transversion in codon 12 and consequently encodes cysteine instead of glycine in normal rat c-Ki-ras. PMID:3023884

Effect of Rhythmic Auditory Stimulation on Hemiplegic Gait Patterns.

PubMed

Shin, Yoon-Kyum; Chong, Hyun Ju; Kim, Soo Ji; Cho, Sung-Rae

2015-11-01

The purpose of our study was to investigate the effect of gait training with rhythmic auditory stimulation (RAS) on both kinematic and temporospatial gait patterns in patients with hemiplegia. Eighteen hemiplegic patients diagnosed with either cerebral palsy or stroke participated in this study. All participants underwent the 4-week gait training with RAS. The treatment was performed for 30 minutes per each session, three sessions per week. RAS was provided with rhythmic beats using a chord progression on a keyboard. Kinematic and temporospatial data were collected and analyzed using a three-dimensional motion analysis system. Gait training with RAS significantly improved both proximal and distal joint kinematic patterns in hip adduction, knee flexion, and ankle plantar flexion, enhancing the gait deviation index (GDI) as well as ameliorating temporal asymmetry of the stance and swing phases in patients with hemiplegia. Stroke patients with previous walking experience demonstrated significant kinematic improvement in knee flexion in mid-swing and ankle dorsiflexion in terminal stance. Among stroke patients, subacute patients showed a significantly increased GDI score compared with chronic patients. In addition, household ambulators showed a significant effect on reducing anterior tilt of the pelvis with an enhanced GDI score, while community ambulators significantly increased knee flexion in mid-swing phase and ankle dorsiflexion in terminal stance phase. Gait training with RAS has beneficial effects on both kinematic and temporospatial patterns in patients with hemiplegia, providing not only clinical implications of locomotor rehabilitation with goal-oriented external feedback using RAS but also differential effects according to ambulatory function.

The potential of targeting Ras proteins in lung cancer.

PubMed

McCormick, Frank

2015-04-01

The Ras pathway is a major driver in lung adenocarcinoma: over 75% of all cases harbor mutations that activate this pathway. While spectacular clinical successes have been achieved by targeting activated receptor tyrosine kinases in this pathway, little, if any, significant progress has been achieved targeting Ras proteins themselves or cancers driven by oncogenic Ras mutants. New approaches to drug discovery, new insights into Ras function, new ways of attacking undruggable proteins through RNA interference and new ways of harnessing the immune system could change this landscape in the relatively near future.

Ras trafficking, localization and compartmentalized signalling

PubMed Central

Prior, Ian A.; Hancock, John F.

2012-01-01

Ras proteins are proto-oncogenes that are frequently mutated in human cancers. Three closely related isoforms, HRAS, KRAS and NRAS, are expressed in all cells and have overlapping but distinctive functions. Recent work has revealed how differences between the Ras isoforms in their trafficking, localization and protein-membrane orientation enable signalling specificity to be determined. We review the various strategies used to characterize compartmentalized Ras localization and signalling. Localization is an important contextual modifier of signalling networks and insights from the Ras system are of widespread relevance for researchers interested in signalling initiated from membranes. PMID:21924373

Graded inhibition of oncogenic Ras-signaling by multivalent Ras-binding domains

PubMed Central

2014-01-01

Background Ras is a membrane-associated small G-protein that funnels growth and differentiation signals into downstream signal transduction pathways by cycling between an inactive, GDP-bound and an active, GTP-bound state. Aberrant Ras activity as a result of oncogenic mutations causes de novo cell transformation and promotes tumor growth and progression. Results Here, we describe a novel strategy to block deregulated Ras activity by means of oligomerized cognate protein modules derived from the Ras-binding domain of c-Raf (RBD), which we named MSOR for multivalent scavengers of oncogenic Ras. The introduction of well-characterized mutations into RBD was used to adjust the affinity and hence the blocking potency of MSOR towards activated Ras. MSOR inhibited several oncogenic Ras-stimulated processes including downstream activation of Erk1/2, induction of matrix-degrading enzymes, cell motility and invasiveness in a graded fashion depending on the oligomerization grade and the nature of the individual RBD-modules. The amenability to accurate experimental regulation was further improved by engineering an inducible MSOR-expression system to render the reversal of oncogenic Ras effects controllable. Conclusion MSOR represent a new tool for the experimental and possibly therapeutic selective blockade of oncogenic Ras signals. PMID:24383791

Improving Watershed-Scale Hydrodynamic Models by Incorporating Synthetic 3D River Bathymetry Network

NASA Astrophysics Data System (ADS)

Dey, S.; Saksena, S.; Merwade, V.

2017-12-01

Digital Elevation Models (DEMs) have an incomplete representation of river bathymetry, which is critical for simulating river hydrodynamics in flood modeling. Generally, DEMs are augmented with field collected bathymetry data, but such data are available only at individual reaches. Creating a hydrodynamic model covering an entire stream network in the basin requires bathymetry for all streams. This study extends a conceptual bathymetry model, River Channel Morphology Model (RCMM), to estimate the bathymetry for an entire stream network for application in hydrodynamic modeling using a DEM. It is implemented at two large watersheds with different relief and land use characterizations: coastal Guadalupe River basin in Texas with flat terrain and a relatively urban White River basin in Indiana with more relief. After bathymetry incorporation, both watersheds are modeled using HEC-RAS (1D hydraulic model) and Interconnected Pond and Channel Routing (ICPR), a 2-D integrated hydrologic and hydraulic model. A comparison of the streamflow estimated by ICPR at the outlet of the basins indicates that incorporating bathymetry influences streamflow estimates. The inundation maps show that bathymetry has a higher impact on flat terrains of Guadalupe River basin when compared to the White River basin.

Local bone marrow renin-angiotensin system in primitive, definitive and neoplastic haematopoiesis.

PubMed

Haznedaroglu, Ibrahim C; Beyazit, Yavuz

2013-03-01

The locally active ligand peptides, mediators, receptors and signalling pathways of the haematopoietic BM (bone marrow) autocrine/paracrine RAS (renin-angiotensin system) affect the essential steps of definitive blood cell production. Haematopoiesis, erythropoiesis, myelopoiesis, formation of monocytic and lymphocytic lineages, thrombopoiesis and other stromal cellular elements are regulated by the local BM RAS. The local BM RAS is present and active even in primitive embryonic haematopoiesis. ACE (angiotensin-converting enzyme) is expressed on the surface of the first endothelial and haematopoietic cells, forming the marrow cavity in the embryo. ACE marks early haematopoietic precursor cells and long-term blood-forming CD34(+) BM cells. The local autocrine tissue BM RAS may also be active in neoplastic haematopoiesis. Critical RAS mediators such as renin, ACE, AngII (angiotensin II) and angiotensinogen have been identified in leukaemic blast cells. The local tissue RAS influences tumour growth and metastases in an autocrine and paracrine fashion via the modulation of numerous carcinogenic events, such as angiogenesis, apoptosis, cellular proliferation, immune responses, cell signalling and extracellular matrix formation. The aim of the present review is to outline the known functions of the local BM RAS within the context of primitive, definitive and neoplastic haematopoiesis. Targeting the actions of local RAS molecules could represent a valuable therapeutic option for the management of neoplastic disorders.

Positive feedback can lead to dynamic nanometer-scale clustering on cell membranes

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

Wehrens, Martijn; Rein ten Wolde, Pieter; Mugler, Andrew, E-mail: amugler@purdue.edu

2014-11-28

Clustering of molecules on biological membranes is a widely observed phenomenon. A key example is the clustering of the oncoprotein Ras, which is known to be important for signal transduction in mammalian cells. Yet, the mechanism by which Ras clusters form and are maintained remains unclear. Recently, it has been discovered that activated Ras promotes further Ras activation. Here we show using particle-based simulation that this positive feedback is sufficient to produce persistent clusters of active Ras molecules at the nanometer scale via a dynamic nucleation mechanism. Furthermore, we find that our cluster statistics are consistent with experimental observations ofmore » the Ras system. Interestingly, we show that our model does not support a Turing regime of macroscopic reaction-diffusion patterning, and therefore that the clustering we observe is a purely stochastic effect, arising from the coupling of positive feedback with the discrete nature of individual molecules. These results underscore the importance of stochastic and dynamic properties of reaction diffusion systems for biological behavior.« less

Swelling/Floating Capability and Drug Release Characterizations of Gastroretentive Drug Delivery System Based on a Combination of Hydroxyethyl Cellulose and Sodium Carboxymethyl Cellulose

PubMed Central

Chen, Ying-Chen; Ho, Hsiu-O; Liu, Der-Zen; Siow, Wen-Shian; Sheu, Ming-Thau

2015-01-01

The aim of this study was to characterize the swelling and floating behaviors of gastroretentive drug delivery system (GRDDS) composed of hydroxyethyl cellulose (HEC) and sodium carboxymethyl cellulose (NaCMC) and to optimize HEC/NaCMC GRDDS to incorporate three model drugs with different solubilities (metformin, ciprofloxacin, and esomeprazole). Various ratios of NaCMC to HEC were formulated, and their swelling and floating behaviors were characterized. Influences of media containing various NaCl concentrations on the swelling and floating behaviors and drug solubility were also characterized. Finally, release profiles of the three model drugs from GRDDS formulation (F1-4) and formulation (F1-1) were examined. Results demonstrated when the GRDDS tablets were tested in simulated gastric solution, the degree of swelling at 6 h was decreased for each formulation that contained NaCMC in comparison to those in de-ionized water (DIW). Of note, floating duration was enhanced when in simulated gastric solution compared to DIW. Further, the hydration of tablets was found to be retarded as the NaCl concentration in the medium increased resulting in smaller gel layers and swelling sizes. Dissolution profiles of the three model drugs in media containing various concentrations of NaCl showed that the addition of NaCl to the media affected the solubility of the drugs, and also their gelling behaviors, resulting in different mechanisms for controlling a drug’s release. The release mechanism of the freely water-soluble drug, metformin, was mainly diffusion-controlled, while those of the water-soluble drug, ciprofloxacin, and the slightly water-soluble drug, esomeprazole, were mainly anomalous diffusion. Overall results showed that the developed GRDDS composed of HEC 250HHX and NaCMC of 450 cps possessed proper swelling extents and desired floating periods with sustained-release characteristics. PMID:25617891

RAS mutations affect pattern of metastatic spread and increase propensity for brain metastasis in colorectal cancer.

PubMed

Yaeger, Rona; Cowell, Elizabeth; Chou, Joanne F; Gewirtz, Alexandra N; Borsu, Laetitia; Vakiani, Efsevia; Solit, David B; Rosen, Neal; Capanu, Marinela; Ladanyi, Marc; Kemeny, Nancy

2015-04-15

RAS and PIK3CA mutations in metastatic colorectal cancer (mCRC) have been associated with worse survival. We sought to evaluate the impact of RAS and PIK3CA mutations on cumulative incidence of metastasis to potentially curable sites of liver and lung and other sites such as bone and brain. We performed a computerized search of the electronic medical record of our institution for mCRC cases genotyped for RAS or PIK3CA mutations from 2008 to 2012. Cases were reviewed for patient characteristics, survival, and site-specific metastasis. Among the 918 patients identified, 477 cases were RAS wild type, and 441 cases had a RAS mutation (394 at KRAS exon 2, 29 at KRAS exon 3 or 4, and 18 in NRAS). RAS mutation was significantly associated with shorter median overall survival (OS) and on multivariate analysis independently predicted worse OS (HR, 1.6; P < .01). RAS mutant mCRC exhibited a significantly higher cumulative incidence of lung, bone, and brain metastasis and on multivariate analysis was an independent predictor of involvement of these sites (HR, 1.5, 1.6, and 3.7, respectively). PIK3CA mutations occurred in 10% of the 786 cases genotyped, did not predict for worse survival, and did not exhibit a site-specific pattern of metastatic spread. The metastatic potential of CRC varies with the presence of RAS mutation. RAS mutation is associated with worse OS and increased incidence of lung, bone, and brain metastasis. An understanding of this site-specific pattern of spread may help to inform physicians' assessment of symptoms in patients with mCRC. © 2014 American Cancer Society.

Andrographolide derivatives inhibit guanine nucleotide exchange and abrogate oncogenic Ras function

PubMed Central

Hocker, Harrison J.; Cho, Kwang-Jin; Chen, Chung-Ying K.; Rambahal, Nandini; Sagineedu, Sreenivasa Rao; Shaari, Khozirah; Stanslas, Johnson; Hancock, John F.; Gorfe, Alemayehu A.

2013-01-01

Aberrant signaling by oncogenic mutant rat sarcoma (Ras) proteins occurs in ∼15% of all human tumors, yet direct inhibition of Ras by small molecules has remained elusive. Recently, several small-molecule ligands have been discovered that directly bind Ras and inhibit its function by interfering with exchange factor binding. However, it is unclear whether, or how, these ligands could lead to drugs that act against constitutively active oncogenic mutant Ras. Using a dynamics-based pocket identification scheme, ensemble docking, and innovative cell-based assays, here we show that andrographolide (AGP)—a bicyclic diterpenoid lactone isolated from Andrographis paniculata—and its benzylidene derivatives bind to transient pockets on Kirsten-Ras (K-Ras) and inhibit GDP–GTP exchange. As expected for inhibitors of exchange factor binding, AGP derivatives reduced GTP loading of wild-type K-Ras in response to acute EGF stimulation with a concomitant reduction in MAPK activation. Remarkably, however, prolonged treatment with AGP derivatives also reduced GTP loading of, and signal transmission by, oncogenic mutant K-RasG12V. In sum, the combined analysis of our computational and cell biology results show that AGP derivatives directly bind Ras, block GDP–GTP exchange, and inhibit both wild-type and oncogenic K-Ras signaling. Importantly, our findings not only show that nucleotide exchange factors are required for oncogenic Ras signaling but also demonstrate that inhibiting nucleotide exchange is a valid approach to abrogating the function of oncogenic mutant Ras. PMID:23737504

N-ras Mutation Detection by Pyrosequencing in Adult Patients with Acute Myeloid Leukemia at a Single Institution

PubMed Central

Jeong, Ji Hun; Park, Soon Ho; Park, Mi Jung; Kim, Moon Jin; Kim, Kyung Hee; Park, Pil Whan; Seo, Yiel Hea; Lee, Jae Hoon; Park, Jinny; Hong, Junshik

2013-01-01

Background N-ras mutations are one of the most commonly detected abnormalities of myeloid origin. N-ras mutations result in a constitutively active N-ras protein that induces uncontrolled cell proliferation and inhibits apoptosis. We analyzed N-ras mutations in adult patients with AML at a particular institution and compared pyrosequencing analysis with a direct sequencing method for the detection of N-ras mutations. Methods We analyzed 90 bone marrow samples from 83 AML patients. We detected N-ras mutations in codons 12, 13, and 61 using the pyrosequencing method and subsequently confirmed all data by direct sequencing. Using these methods, we screened the N-ras mutation quantitatively and determined the incidence and characteristic of N-ras mutation. Results The incidence of N-ras mutation was 7.2% in adult AML patients. The patients with N-ras mutations showed significant higher hemoglobin levels (P=0.022) and an increased incidence of FLT3 mutations (P=0.003). We observed 3 cases with N-ras mutations in codon 12 (3.6%), 2 cases in codon 13 (2.4%), and 1 case in codon 61 (1.2%). All the mutations disappeared during chemotherapy. Conclusions There is a low incidence (7.2%) of N-ras mutations in AML patients compared with other populations. Similar data is obtained by both pyrosequencing and direct sequencing. This study showed the correlation between the N-ras mutation and the therapeutic response. However, pyrosequencing provides quantitative data and is useful for monitoring therapeutic responses. PMID:23667841

Oncogenic Ras induces inflammatory cytokine production by up-regulating the squamous cell carcinoma antigens SerpinB3/B4

PubMed Central

Pan, Ji-An; Sun, Yu; Shi, Chanjuan; Li, Jinyu; Powers, R. Scott; Crawford, Howard C.; Zong, Wei-Xing

2014-01-01

Mounting evidence indicates that oncogenic Ras can modulate cell autonomous inflammatory cytokine production, although the underlying mechanism remains unclear. Here we show that squamous cell carcinoma antigens 1 and 2 (SCCA1/2), members of the Serpin family of serine/cysteine protease inhibitors, are transcriptionally up-regulated by oncogenic Ras via MAPK and the ETS family transcription factor PEA3. Increased SCCA expression leads to inhibition of protein turnover, unfolded protein response, activation of NF-κB, and is essential for Ras-mediated cytokine production and tumor growth. Analysis of human colorectal and pancreatic tumor samples reveals a positive correlation between Ras mutation, enhanced SCCA expression, and IL-6 expression. These results indicate that SCCA is a Ras-responsive factor that has a role in Ras-associated cytokine production and tumorigenesis. PMID:24759783

Suitability Measurement and Analysis for Fort Bliss Naval Air Facility OLS. Opportune Landing Site Program

DTIC Science & Technology

2008-09-01

bushes on the RAS. ERDC/CRREL TR-08-16 71 d. Delphinium virescens.4 e. Nolina microcarpa .5 f. Lygodesmia exigua.6 Figure 27 (cont’d...4 There are a few of these plants along the RAS. 5 There are a few nolinas on the RAS

A PLC-γ1-independent, RasGRP1-ERK dependent pathway drives lymphoproliferative disease in LAT-Y136F mutant mice

PubMed Central

Kortum, Robert L.; Rouquette-Jazdanian, Alexandre K.; Miyaji, Michihiko; Merrill, Robert K.; Markegard, Evan; Pinski, John M.; Wesselink, Amelia; Nath, Nandan N.; Alexander, Clayton P.; Li, Wenmei; Kedei, Noemi; Roose, Jeroen P.; Blumberg, Peter M.; Samelson, Lawrence E.; Sommers, Connie L.

2012-01-01

Mice expressing a germline mutation in the PLC-γ1 binding site of LAT (linker for activation of T cells) show progressive lymphoproliferation and ultimately die at 4–6 months of age. The hyper-activated T cells in these mice show defective TCR-induced calcium flux, but enhanced Ras/ERK activation that is critical for disease progression. Despite the loss of LAT-dependent PLC-γ1 binding and activation, genetic analysis revealed RasGRP1, and not Sos1 or Sos2, to be the major RasGEF responsible for ERK activation and the lymphoproliferative phenotype in these mice. Analysis of isolated CD4+ T cells from LAT-Y136F mice showed altered proximal TCR-dependent kinase signaling, which activated a Zap70- and LAT-independent pathway. Moreover, LAT-Y136F T cells showed ERK activation that was dependent on Lck and/or Fyn, PKCθ, and RasGRP1. These data demonstrate a novel route to Ras activation in vivo in a pathological setting. PMID:23209318

Upregulation of c-mesenchymal epithelial transition expression and RAS mutations are associated with late lung metastasis and poor prognosis in colorectal carcinoma.

PubMed

Liu, Jianhua; Zeng, Weiqiang; Huang, Chengzhi; Wang, Junjiang; Xu, Lishu; Ma, Dong

2018-05-01

The present study aimed to investigate whether c-mesenchymal epithelial transition factor (C-MET) overexpression combined with RAS (including KRAS, NRAS and HRAS ) or BRAF mutations were associated with late distant metastases and the prognosis of patients with colorectal cancer (CRC). A total of 374 patients with stage III CRC were classified into 4 groups based on RAS/BRAF and C-MET status for comprehensive analysis. Mutations in RAS / BRAF were determined using Sanger sequencing and C-MET expression was examined using immunohistochemistry. The associations between RAS/BRAF mutations in combination with C-MET overexpression and clinicopathological variables including survival were evaluated. In addition, their predictive value for late distant metastases were statistically analyzed via logistic regression and receiver operating characteristic analysis. Among 374 patients, mutations in KRAS, NRAS, HRAS, BRAF and C-MET overexpression were observed in 43.9, 2.4, 0.3, 5.9 and 71.9% of cases, respectively. Considering RAS/BRAF mutations and C-MET overexpression, vascular invasion (P=0.001), high carcino-embryonic antigen level (P=0.031) and late distant metastases (P<0.001) were more likely to occur in patients of group 4. Furthermore, survival analyses revealed RAS/BRAF mutations may have a more powerful impact on survival than C-MET overexpression, although they were both predictive factors for adverse prognosis. Further logistic regression suggested that RAS/BRAF mutations and C-MET overexpression may predict late distant metastases. In conclusion, RAS/BRAF mutations and C-MET overexpression may serve as predictive indicators for metastatic behavior and poor prognosis of CRC.

RAS testing of liquid biopsy correlates with the outcome of metastatic colorectal cancer patients treated with first-line FOLFIRI plus cetuximab in the CAPRI-GOIM trial.

PubMed

Normanno, N; Esposito Abate, R; Lambiase, M; Forgione, L; Cardone, C; Iannaccone, A; Sacco, A; Rachiglio, A M; Martinelli, E; Rizzi, D; Pisconti, S; Biglietto, M; Bordonaro, R; Troiani, T; Latiano, T P; Giuliani, F; Leo, S; Rinaldi, A; Maiello, E; Ciardiello, F

2018-01-01

Liquid biopsy is an alternative to tissue for RAS testing in metastatic colorectal carcinoma (mCRC) patients. Little information is available on the predictive role of liquid biopsy RAS testing in patients treated with first-line anti-EGFR monoclonal antibody-based therapy. In the CAPRI-GOIM trial, 340 KRAS exon-2 wild-type mCRC patients received first-line cetuximab plus FOLFIRI. Tumor samples were retrospectively assessed by next generation sequencing (NGS). Baseline plasma samples were analyzed for KRAS and NRAS mutations using beads, emulsion, amplification, and magnetics digital PCR (BEAMing). Discordant cases were solved by droplet digital PCR (ddPCR) or deep-sequencing. A subgroup of 92 patients with available both NGS data on tumor samples and baseline plasma samples were included in this study. Both NGS analysis of tumor tissue and plasma testing with BEAMing identified RAS mutations in 33/92 patients (35.9%). However, 10 cases were RAS tissue mutant and plasma wild-type, and additional 10 cases were tissue wild-type and plasma mutant, resulting in a concordance rate of 78.3%. Analysis of plasma samples with ddPCR detected RAS mutations in 2/10 tissue mutant, plasma wild-type patients. In contrast, in all tissue wild-type and plasma mutant cases, ddPCR or deep-sequencing analysis of tumor tissue confirmed the presence of RAS mutations at allelic frequencies ranging between 0.15% and 1.15%. The median progression-free survival of RAS mutant and wild-type patients according to tissue (7.9 versus 12.6 months; P = 0.004) and liquid biopsy testing (7.8 versus 13.8 moths; P < 0.001) were comparable. Similar findings were observed for the median overall survival of RAS mutant and wild-type patients based on tissue (22.1 versus 35.8 months; P = 0.016) and plasma (19.9 versus 35.8 months; P = 0.013) analysis. This study indicates that RAS testing of liquid biopsy results in a similar outcome when compared with tissue testing in mCRC patients receiving first-line anti-EGFR monoclonal antibodies. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

The Remote Analysis Station (RAS) as an instructional system

NASA Technical Reports Server (NTRS)

Rogers, R. H.; Wilson, C. L.; Dye, R. H.; Jaworski, E.

1981-01-01

"Hands-on" training in LANDSAT data analysis techniques can be obtained using a desk-top, interactive remote analysis station (RAS) which consists of a color CRT imagery display, with alphanumeric overwrite and keyboard, as well as a cursor controller and modem. This portable station can communicate via modem and dial-up telephone with a host computer at 1200 baud or it can be hardwired to a host computer at 9600 baud. A Z80 microcomputer controls the display refresh memory and remote station processing. LANDSAT data is displayed as three-band false-color imagery, one-band color-sliced imagery, or color-coded processed imagery. Although the display memory routinely operates at 256 x 256 picture elements, a display resolution of 128 x 128 can be selected to fill the display faster. In the false color mode the computer packs the data into one 8-bit character. When the host is not sending pictorial information the characters sent are in ordinary ASCII code. System capabilities are described.

Renin angiotensin system blockers-associated angioedema in the Thai population: analysis from Thai National Pharmacovigilance Database.

PubMed

Win, Thet Su Zin; Chaiyakunapruk, Nathorn; Suwankesawong, Wimon; Dilokthornsakul, Piyameth; Nathisuwan, Surakit

2015-09-01

Renin-angiotensin-aldosterone system (RAS) blockers are commonly used for cardiovascular diseases. Currently, little information exists for the Asian population on angioedema, a rare yet serious adverse event. This study aimed to describe characteristics of RAS blockers-associated angioedema (RASBA) in Thai patients. A retrospective study using the national pharmacovigilance database of Thailand was undertaken. Cases indicating the presence of angioedema with RAS blockers uses from 1984-2011 were identified. Patient demographics, co-morbidities, concomitant drugs, information for the RAS blockers and angioedema were obtained as well as causality assessment and quality of reports. A total of 895 cases were identified. Mean age was 59.9+12.8 years and 66.5% being female. Most angioedema events (48.6%) occurred during the first week of treatment. Angiotensin converting enzyme inhibitors (87.7%) were the most commonly implicated agents followed by angiotensin receptor blockers (10.5%), aldosterone antagonist (2.1%) and direct renin inhibitor (0.2%). Out of the 895 cases incorporated in this study, 165 (18.4%) were classified as serious events and resulted in hospitalization. The overall case fatality rate was 0.4%. Respiratory disturbance occurred in 46 cases (5.1%). Patients with respiratory complications tended to be younger (53.4+13.9 vs 60.3+12.7 years old; p=0.002) and with higher frequency of allergy history (26.1% vs 14.7%; p=0.032) compared to those without respiratory complications. Based on multivariate logistic regression, the adjusted OR for history of allergy was 2.23 (95%CI: 1.04 - 4.78, p = 0.041). RASBA in Thai population occurred mostly in elderly female patients and often led to hospitalization. Since large number of patients is regularly exposed to RAS-blockers, a nationwide attempt to raise awareness of clinicians when prescribing RAS-blockers is prudent.

Some Comparative Aspects of the Renin-Angiotensin System.

ERIC Educational Resources Information Center

Malvin, Richard L.

1984-01-01

The renin-angiotensin system (RAS) maintains salt and water balance. Discusses functions of the RAS as defined in mammalian species, considering how the system arose and what its original function was. Also discusses where some of the changes occurred in the system (and why) as well as other topics. (JN)

Nonaqueous lithium-ion capacitors with high energy densities using trigol-reduced graphene oxide nanosheets as cathode-active material.

PubMed

Aravindan, Vanchiappan; Mhamane, Dattakumar; Ling, Wong Chui; Ogale, Satishchandra; Madhavi, Srinivasan

2013-12-01

One HEC of a material: The use of trigol-reduced graphene oxide nanosheets as cathode material in hybrid lithium-ion electrochemical capacitors (Li-HECs) results in an energy density of 45 Wh kg(-1) ; much enhanced when compared to similar devices. The mass loading of the active materials is optimized, and the devices show good cycling performance. Li-HECs employing these materials outperform other supercapacitors, making them attractive for use in power sources. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Loss of Life, Evacuation and Emergency Management - Application of Dutch Models to US Case Studies

DTIC Science & Technology

2012-12-18

Risks to people M es o: Z on e or lo ca tio n Instability tests Jonkman 1953 D eK ay a nd M cC le lla nd G ra ha m Katrina HEC -FIA...mortality functions (Jonkman) o 2.2.2 New Orleans / Katrina mortality functions (Jonkman) o 2.2.3 HEC FIA approach (USACE) o 2.2.4. Loss of life methods...comparison (USACE) • 2.3 Dutch Evacuation and Evacuaid approach (Kolen) o 2.3.1 Evacuation approach implemented in HEC FIA (USACE) o 2.3.2 Evacuation

Ethiopian Central Rift Valley basin hydrologic modelling using HEC-HMS and ArcSWAT

NASA Astrophysics Data System (ADS)

Pascual-Ferrer, Jordi; Candela, Lucila; Pérez-Foguet, Agustí

2013-04-01

An Integrated Water Resources Management (IWRM) shall be applied to achieve a sustainable development, to increase population incomes without affecting lives of those who are highly dependent on the environment. First step should be to understand water dynamics at basin level, starting by modeling the basin water resources. For model implementation, a large number of data and parameters are required, but those are not always available, especially in some developing countries where different sources may have different data, there is lack of information on data collection, etc. The Ethiopian Central Rift Valley (CRV) is an endorheic basin covering an area of approximately 10,000 km2. For the period 1996-2005, the average annual volume of rainfall accounted for 9.1 Mm3, and evapotranspiration for 8 Mm3 (Jansen et al., 2007). From the environmental point of view, basin ecosystems are endangered due to human activities. Also, poverty is widespread all over the basin, with population mainly living from agriculture on a subsistence economy. Hence, there is an urgent need to set an IWRM, but datasets required for water dynamics simulation are not too reliable. In order to reduce uncertainty of numerical simulation, two semi-distributed open software hydrologic models were implemented: HEC-HMS and ArcSWAT. HEC-HMS was developed by the United States Army Corps of Engineers (USACoE) Hydrologic Engineering Center (HEC) to run precipitation-runoff simulations for a variety of applications in dendritic watershed systems. ArcSWAT includes the SWAT (Soil and Water Assessment Tool, Arnold et al., 1998) model developed for the USDA Agricultural Research Service into ArcGIS (ESRI®). SWAT was developed to assess the impact of land management practices on large complex watersheds with varying soils, land use and management conditions over long periods of time (Neitsch et al., 2005). According to this, ArcSWAT would be the best option for IWRM implementation in the basin. However, considering data uncertainty and model complexity a previous hydrologic assessment of the basin based in HEC-HMS simulation is advisable. As a first approach HEC-HMS was implemented for basin modeling in order to get physical parameters of interest, results from HEC-HMS calibration were used to setup the accuracy of the ArcSWAT numerical modelling. References Arnold, J.G., Srinivasan, R., Muttiah, R.S. & Williams, J.R. (1998). Large Area Hydrologic Modeling and Assessment Part I: Model Development. JAWRA Journal of the American Water Resources Association, Vol. 34, No. 1, pp. 73-89. Jansen, H., Hengsdijk, H., Legesse, D., Ayenew, T., Hellegers, P. & Spliethoff, P. (2007). Land and water resources assessment in the Ethiopian Central Rift Valley. In Alterra report 1587. Wageningen: Alterra. p. 81. Neitsch, S.L., Arnold, J.G., Kiniry, J.R. & Williams, J.R. (2005). Soil and Water Assessment Tool Theoretical Documentation. Version 2005, Temple, Texas.

Bacillus subtilis Intramembrane Protease RasP Activity in Escherichia coli and In Vitro.

PubMed

Parrell, Daniel; Zhang, Yang; Olenic, Sandra; Kroos, Lee

2017-10-01

RasP is a predicted intramembrane metalloprotease of Bacillus subtilis that has been proposed to cleave the stress response anti-sigma factors RsiW and RsiV, the cell division protein FtsL, and remnant signal peptides within their transmembrane segments. To provide evidence for direct effects of RasP on putative substrates, we developed a heterologous coexpression system. Since expression of catalytically inactive RasP E21A inhibited expression of other membrane proteins in Escherichia coli , we added extra transmembrane segments to RasP E21A, which allowed accumulation of most other membrane proteins. A corresponding active version of RasP appeared to promiscuously cleave coexpressed membrane proteins, except those with a large periplasmic domain. However, stable cleavage products were not observed, even in clpP mutant E. coli Fusions of transmembrane segment-containing parts of FtsL and RsiW to E. coli maltose-binding protein (MBP) also resulted in proteins that appeared to be RasP substrates upon coexpression in E. coli , including FtsL with a full-length C-terminal domain (suggesting that prior cleavage by a site 1 protease is unnecessary) and RsiW designed to mimic the PrsW site 1 cleavage product (suggesting that further trimming by extracytoplasmic protease is unnecessary). Purified RasP cleaved His 6 -MBP-RsiW(73-118) in vitro within the RsiW transmembrane segment based on mass spectrometry analysis, demonstrating that RasP is an intramembrane protease. Surprisingly, purified RasP failed to cleave His 6 -MBP-FtsL(23-117). We propose that the lack of α-helix-breaking residues in the FtsL transmembrane segment creates a requirement for the membrane environment and/or an additional protein(s) in order for RasP to cleave FtsL. IMPORTANCE Intramembrane proteases govern important signaling pathways in nearly all organisms. In bacteria, they function in stress responses, cell division, pathogenesis, and other processes. Their membrane-associated substrates are typically inferred from genetic studies in the native bacterium. Evidence for direct effects has come sometimes from coexpression of the enzyme and potential substrate in a heterologous host and rarely from biochemical reconstitution of cleavage in vitro We applied these two approaches to the B. subtilis enzyme RasP and its proposed substrates RsiW and FtsL. We discovered potential pitfalls and solutions in heterologous coexpression experiments in E. coli , providing evidence that both substrates are cleaved by RasP in vivo but, surprisingly, that only RsiW was cleaved in vitro , suggesting that FtsL has an additional requirement. Copyright © 2017 American Society for Microbiology.

Imaging of Ras/Raf activity induced by low energy laser irradiation in living cell using FRET

NASA Astrophysics Data System (ADS)

Wang, Fang; Chen, Tong-Sheng; Xing, Da

2005-01-01

Ras/Raf signaling pathway is an important signaling pathway that governs cell proliferation, differential and apoptosis. Low-energy laser irradiation (LELI) was found to modulate various processes. Generally, cell proliferation is induced by low doses LELI and apoptosis is induced by high doses LELI. Mechanism of biological effect of LELI has not been clear. Recently, activation of MEK (mitogen-activated protein kinase) and ERK (extracellular-signal-regulated kinase), which are downstream protein kinases of Ras/Raf, are observed during LELI-induced cell proliferation by immunoprecipitation and western blot analysis. RaichuRas reporter consisting of fusions of H-ras, the Ras-binding domain of Raf (RafRBD), a cyan fluorescent protein (CFP) and a yellow fluorescent protein (YFP). Therefore, intramolecular binding of GTP-Ras to RafRBD brings CFP close to YFP and increases FRET between CFP and YFP. Human lung adenocarcinoma cell line (ASTC-a-1) was transfected with the plasmid (pRaichuRas) and then treated with LELI at dose of 60J/cm2. Effect of LELI on Ras/Raf in physiological condition of living cells was observed by fluorescence resonance energy transfer (FRET) technique during lung adenocarcinoma cell apoptosis induced by high dose (60J/cm2) LELI. Experimental results showed that after high dose LELI treatment, the binding of Ras and Raf decreases obviously, Ras/Raf signaling pathway deregulates and cell apoptosis occurs.

Ovarian expression of cellular Ki-ras p21 varies with physiological status.

PubMed Central

Palejwala, S; Goldsmith, L T

1992-01-01

To elucidate the potential role of the ras protooncogene proteins in a specific tissue, the present study determined the levels of individual c-ras-encoded p21 proteins in the rat ovary during various stages of physiological function. p21 protein was extracted from ovaries taken from immature normal female rats, mature nonpregnant animals in the metestrus stage of the estrus cycle, rats at various stages of pregnancy, and actively lactating animals. Levels of individual p21s were evaluated by immunoblot analysis with specific antibodies to the p21 proteins encoded by the Kirsten, Harvey, and neuroblastoma c-ras protooncogenes, c-Ki-ras, c-Ha-ras, and N-ras. Results showed that c-Ki-ras p21 is at its lowest level in the immature ovary and increases with development of the corpora lutea to its highest levels at day 16 of pregnancy, after which levels decline and then rise again during lactation. This pattern, which mimics that of circulating progesterone levels, suggests that ovarian c-Ki-ras p21 levels are regulated and that c-Ki-ras p21 plays a role in the differentiated function of the rat ovary, likely the luteal compartment. In contrast, levels of c-N-ras p21 did not appear to vary with changes in the physiological function of the ovary but appeared to be constitutive. A preferential role for the c-Ki-ras p21 may be due to the documented unique differences in the structure of the carboxyl terminus of this particular c-ras p21. Images PMID:1570348

Effect of Rhythmic Auditory Stimulation on Hemiplegic Gait Patterns

PubMed Central

Shin, Yoon-Kyum; Chong, Hyun Ju

2015-01-01

Purpose The purpose of our study was to investigate the effect of gait training with rhythmic auditory stimulation (RAS) on both kinematic and temporospatial gait patterns in patients with hemiplegia. Materials and Methods Eighteen hemiplegic patients diagnosed with either cerebral palsy or stroke participated in this study. All participants underwent the 4-week gait training with RAS. The treatment was performed for 30 minutes per each session, three sessions per week. RAS was provided with rhythmic beats using a chord progression on a keyboard. Kinematic and temporospatial data were collected and analyzed using a three-dimensional motion analysis system. Results Gait training with RAS significantly improved both proximal and distal joint kinematic patterns in hip adduction, knee flexion, and ankle plantar flexion, enhancing the gait deviation index (GDI) as well as ameliorating temporal asymmetry of the stance and swing phases in patients with hemiplegia. Stroke patients with previous walking experience demonstrated significant kinematic improvement in knee flexion in mid-swing and ankle dorsiflexion in terminal stance. Among stroke patients, subacute patients showed a significantly increased GDI score compared with chronic patients. In addition, household ambulators showed a significant effect on reducing anterior tilt of the pelvis with an enhanced GDI score, while community ambulators significantly increased knee flexion in mid-swing phase and ankle dorsiflexion in terminal stance phase. Conclusion Gait training with RAS has beneficial effects on both kinematic and temporospatial patterns in patients with hemiplegia, providing not only clinical implications of locomotor rehabilitation with goal-oriented external feedback using RAS but also differential effects according to ambulatory function. PMID:26446657

Intrinsic K-Ras dynamics: A novel molecular dynamics data analysis method shows causality between residue pair motions

NASA Astrophysics Data System (ADS)

Vatansever, Sezen; Gümüş, Zeynep H.; Erman, Burak

2016-11-01

K-Ras is the most frequently mutated oncogene in human cancers, but there are still no drugs that directly target it in the clinic. Recent studies utilizing dynamics information show promising results for selectively targeting mutant K-Ras. However, despite extensive characterization, the mechanisms by which K-Ras residue fluctuations transfer allosteric regulatory information remain unknown. Understanding the direction of information flow can provide new mechanistic insights for K-Ras targeting. Here, we present a novel approach -conditional time-delayed correlations (CTC) - using the motions of all residue pairs of a protein to predict directionality in the allosteric regulation of the protein fluctuations. Analyzing nucleotide-dependent intrinsic K-Ras motions with the new approach yields predictions that agree with the literature, showing that GTP-binding stabilizes K-Ras motions and leads to residue correlations with relatively long characteristic decay times. Furthermore, our study is the first to identify driver-follower relationships in correlated motions of K-Ras residue pairs, revealing the direction of information flow during allosteric modulation of its nucleotide-dependent intrinsic activity: active K-Ras Switch-II region motions drive Switch-I region motions, while α-helix-3L7 motions control both. Our results provide novel insights for strategies that directly target mutant K-Ras.

The cornerstone K-RAS mutation in pancreatic adenocarcinoma: From cell signaling network, target genes, biological processes to therapeutic targeting.

PubMed

Jonckheere, Nicolas; Vasseur, Romain; Van Seuningen, Isabelle

2017-03-01

RAS belongs to the super family of small G proteins and plays crucial roles in signal transduction from membrane receptors in the cell. Mutations of K-RAS oncogene lead to an accumulation of GTP-bound proteins that maintains an active conformation. In the pancreatic ductal adenocarcinoma (PDAC), one of the most deadly cancers in occidental countries, mutations of the K-RAS oncogene are nearly systematic (>90%). Moreover, K-RAS mutation is the earliest genetic alteration occurring during pancreatic carcinogenetic sequence. In this review, we discuss the central role of K-RAS mutations and their tremendous diversity of biological properties by the interconnected regulation of signaling pathways (MAPKs, NF-κB, PI3K, Ral…). In pancreatic ductal adenocarcinoma, transcriptome analysis and preclinical animal models showed that K-RAS mutation alters biological behavior of PDAC cells (promoting proliferation, migration and invasion, evading growth suppressors, regulating mucin pattern, and miRNA expression). K-RAS also impacts tumor microenvironment and PDAC metabolism reprogramming. Finally we discuss therapeutic targeting strategies of K-RAS that have been developed without significant clinical success so far. As K-RAS is considered as the undruggable target, targeting its multiple effectors and target genes should be considered as potential alternatives. Copyright © 2017 Elsevier B.V. All rights reserved.

Coordinated Fault-Tolerance for High-Performance Computing Final Project Report

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

Panda, Dhabaleswar Kumar; Beckman, Pete

2011-07-28

With the Coordinated Infrastructure for Fault Tolerance Systems (CIFTS, as the original project came to be called) project, our aim has been to understand and tackle the following broad research questions, the answers to which will help the HEC community analyze and shape the direction of research in the field of fault tolerance and resiliency on future high-end leadership systems. Will availability of global fault information, obtained by fault information exchange between the different HEC software on a system, allow individual system software to better detect, diagnose, and adaptively respond to faults? If fault-awareness is raised throughout the system throughmore » fault information exchange, is it possible to get all system software working together to provide a more comprehensive end-to-end fault management on the system? What are the missing fault-tolerance features that widely used HEC system software lacks today that would inhibit such software from taking advantage of systemwide global fault information? What are the practical limitations of a systemwide approach for end-to-end fault management based on fault awareness and coordination? What mechanisms, tools, and technologies are needed to bring about fault awareness and coordination of responses on a leadership-class system? What standards, outreach, and community interaction are needed for adoption of the concept of fault awareness and coordination for fault management on future systems? Keeping our overall objectives in mind, the CIFTS team has taken a parallel fourfold approach. Our central goal was to design and implement a light-weight, scalable infrastructure with a simple, standardized interface to allow communication of fault-related information through the system and facilitate coordinated responses. This work led to the development of the Fault Tolerance Backplane (FTB) publish-subscribe API specification, together with a reference implementation and several experimental implementations on top of existing publish-subscribe tools. We enhanced the intrinsic fault tolerance capabilities representative implementations of a variety of key HPC software subsystems and integrated them with the FTB. Targeting software subsystems included: MPI communication libraries, checkpoint/restart libraries, resource managers and job schedulers, and system monitoring tools. Leveraging the aforementioned infrastructure, as well as developing and utilizing additional tools, we have examined issues associated with expanded, end-to-end fault response from both system and application viewpoints. From the standpoint of system operations, we have investigated log and root cause analysis, anomaly detection and fault prediction, and generalized notification mechanisms. Our applications work has included libraries for fault-tolerance linear algebra, application frameworks for coupled multiphysics applications, and external frameworks to support the monitoring and response for general applications. Our final goal was to engage the high-end computing community to increase awareness of tools and issues around coordinated end-to-end fault management.« less

Application of HEC-6 to ephemeral rivers of Arizona

DOT National Transportation Integrated Search

1986-01-01

The U.S. Army Corps of Engineers, computer program HEC-6--"Scour and Deposition in Rivers and Reservoirs" was applied to three ephemeral rivers of Arizona--Agua Fria River, Salt River, and Rillito Creek. The input data development techniques and resu...

Combined Inhibition of the Renin-Angiotensin System and Neprilysin Positively Influences Complex Mitochondrial Adaptations in Progressive Experimental Heart Failure

PubMed Central

Reinders, Jörg; Schröder, Josef; Dietl, Alexander; Schmid, Peter M.; Jungbauer, Carsten; Resch, Markus; Maier, Lars S.; Luchner, Andreas; Birner, Christoph

2017-01-01

Background Inhibitors of the renin angiotensin system and neprilysin (RAS-/NEP-inhibitors) proved to be extraordinarily beneficial in systolic heart failure. Furthermore, compelling evidence exists that impaired mitochondrial pathways are causatively involved in progressive left ventricular (LV) dysfunction. Consequently, we aimed to assess whether RAS-/NEP-inhibition can attenuate mitochondrial adaptations in experimental heart failure (HF). Methods and Results By progressive right ventricular pacing, distinct HF stages were induced in 15 rabbits, and 6 animals served as controls (CTRL). Six animals with manifest HF (CHF) were treated with the RAS-/NEP-inhibitor omapatrilat. Echocardiographic studies and invasive blood pressure measurements were undertaken during HF progression. Mitochondria were isolated from LV tissue, respectively, and further worked up for proteomic analysis using the SWATH technique. Enzymatic activities of citrate synthase and the electron transfer chain (ETC) complexes I, II, and IV were assessed. Ultrastructural analyses were performed by transmission electron microscopy. During progression to overt HF, intricate expression changes were mainly detected for proteins belonging to the tricarboxylic acid cycle, glucose and fat metabolism, and the ETC complexes, even though ETC complex I, II, or IV enzymatic activities were not significantly influenced. Treatment with a RAS-/NEP-inhibitor then reversed some maladaptive metabolic adaptations, positively influenced the decline of citrate synthase activity, and altered the composition of each respiratory chain complex, even though this was again not accompanied by altered ETC complex enzymatic activities. Finally, ultrastructural evidence pointed to a reduction of autophagolytic and degenerative processes with omapatrilat-treatment. Conclusions This study describes complex adaptations of the mitochondrial proteome in experimental tachycardia-induced heart failure and shows that a combined RAS-/NEP-inhibition can beneficially influence mitochondrial key pathways. PMID:28076404

Angiotensin peptides in the non-gravid uterus: Paracrine actions beyond circulation.

PubMed

Casalechi, Maíra; Dela Cruz, Cynthia; Lima, Luiza C; Maciel, Luciana P; Pereira, Virgínia M; Reis, Fernando M

2018-03-01

The renin-angiotensin system (RAS) involves a complex network of precursors, peptides, enzymes and receptors comprising a systemic (endocrine) and a local (paracrine/autocrine) system. The local RAS plays important roles in tissue modulation and may operate independently of or in close interaction with the circulatory RAS, acting in a complementary fashion. Angiotensin (Ang) II, its receptor AT 1 and Ang-(1-7) expression in the endometrium vary with menstrual cycle, and stromal cell decidualization in vitro is accompanied by local synthesis of angiotensinogen and prorenin. Mas receptor is unlikely to undergo marked changes accompanying the cyclic ovarian steroid hormone fluctuations. Studies investigating the functional relevance of the RAS in the non-gravid uterus show a number of paracrine effects beyond circulation and suggest that RAS peptides may be involved in the pathophysiology of proliferative and fibrotic diseases. Endometrial cancer is associated with increased expression of Ang II, Ang-converting enzyme 1 and AT 1 in the tumoral tissue compared to neighboring non-neoplastic endometrium, and also with a gene polymorphism that enhances AT 1 signal. Ang II induces human endometrial cells to transdifferentiate into cells with myofibroblast phenotype and to synthetize extracellular matrix components that might contribute to endometrial fibrosis. Altogether, these findings point to a fully operating RAS within the uterus, but since many concepts rely on preliminary evidence further studies are needed to clarify the role of the local RAS in uterine physiology and pathophysiology. Copyright © 2018 Elsevier Inc. All rights reserved.

The Non-Classical Renin-Angiotensin System and Renal Function

PubMed Central

Chappell, Mark C.

2014-01-01

The renin-angiotensin-system (RAS) constitutes one of the most important hormonal systems in the physiological regulation of blood pressure through renal and non-renal mechanisms. Indeed, dysregulation of the RAS is considered a major factor in the development of cardiovascular pathologies including kidney injury and blockade of this system by the inhibition of angiotensin converting enzyme (ACE) or blockade of the angiotensin type 1 receptor (AT1R) by selective antagonists constitutes an effective therapeutic regimen. It is now apparent with the identification of multiple components of the RAS within the kidney and other tissues that the system is actually composed of different angiotensin peptides with diverse biological actions mediated by distinct receptor subtypes. The classic RAS can be defined as the ACE-Ang II AT1R axis that promotes vasoconstriction, water intake, sodium retention and other mechanisms to maintain blood pressure, as well as increase oxidative stress, fibrosis, cellular growth and inflammation in pathological conditions. In contrast, the non-classical RAS composed primarily of the AngII/Ang III–AT2R pathway and the ACE2-Ang-(1-7)-AT7R axis generally opposes the actions of a stimulated Ang II-AT1R axis through an increase in nitric oxide and prostaglandins and mediates vasodilation, natriuresis, diuresis, and a reduced oxidative stress. Moreover, increasing evidence suggests that these non-classical RAS components contribute to the therapeutic blockade of the classical system to reduce blood pressure and attenuate various indices of renal injury, as well as contribute to normal renal function. PMID:23720263

p21ras independent down-regulation of ras-induced increases in natural antibody binding during tumor progression.

PubMed

Tough, D F; Feng, X; Chow, D A

1995-01-01

Selective outgrowth of v-H-ras-infected 10T1/2 cells based on the cointroduction of a gene for resistance to geneticin (G418), yielded cells which exhibited an increased capacity to bind polyclonal serum natural antibody (NAb). This demonstrated an NAb-susceptible phase of tumor development which would be a basic requirement for NAb-mediated surveillance of tumors. The ras-oncogene dependence of the high-NAb-binding phenotype provided a model for assessing NAb resistance against ras transformants in vivo and for a comparative analysis of phenotypic and genetic alterations contributing to the progression of ras transformants. Variants were developed through in vitro and in vivo models of tumor progression. T24-H-ras and v-H-ras transformants were isolated in vitro through more rigorous growth conditions, focus formation in the presence of untransformed cells with no selecting drug. These clones expressed p21ras but exhibited little or no increase in NAb binding. Variants recovered following growth from intravenous or threshold subcutaneous (s.c.) inocula of high-NAb-binding ras transformants in syngeneic C3H/HeN mice exhibited decreases in NAb binding but no uniform change in p21ras. Concurring inverse correlations between NAb binding and s.c. tumorigenicity were exhibited by the T24-H-ras transformant clones, the ras transformants grown in vivo, and the v-H-ras-transformed clones isolated in the presence versus the absence of untransformed cells. This consistent inverse correlation, together with the reduced NAb binding of the ras transformants grown in vivo, provides strong evidence that NAb participates in the defense against ras-transformed cells in vivo. The lack of any direct correlation between p21ras expression and the reduction in NAb binding or the increase in tumorigenicity of cells generated through progression in vivo suggested the regulatory action of additional genes. Hybridization studies between high- and low-NAb-binding clones implicated the activation of an additional oncogene and inactivation of an antioncogene in the down-regulation of the ras-induced increases in NAb binding associated with tumor progression.

Losartan, an Angiotensin type I receptor, restores erectile function by downregulation of cavernous renin-angiotensin system in streptozocin-induced diabetic rats.

PubMed

Yang, Rong; Yang, Bin; Wen, Yanting; Fang, Feng; Cui, Souxi; Lin, Guiting; Sun, Zeyu; Wang, Run; Dai, Yutian

2009-03-01

The high incidence of erectile dysfunction (ED) in diabetes highlights the need for good treatment strategies. Recent evidence indicates that blockade of the angiotensin type I receptor (AT1) may reverse ED from various diseases. To explore the role of cavernous renin-angiotensin system (RAS) in the pathogenesis of diabetic ED and the role of losartan in the treatment of diabetic ED. The AT1 blocker (ARB) losartan (30 mg/kg/d) was administered to rats with streptozocin (65 mg/kg)-induced diabetes. Erectile function, cavernous structure, and tissue gene and protein expression of RAS in the corpora cavernosa were studied. We sought to determine the changes of cavernous RAS in the condition of diabetes and after treatment with losartan. RAS components (angiotensinogen, [pro]renin receptor, angiotensin-converting enzyme [ACE], and AT1) were expressed in cavernosal tissue. In diabetic rats, RAS components were upregulated, resulting in the increased concentration of angiotensin II (Ang II) in the corpora. A positive feedback loop for Ang II formation in cavernosum was also identified, which could contribute to overactivity of cavernous RAS in diabetic rats. Administration of losartan blocked the effect of Ang II, downregulated the expression of AT1 and Ang II generated locally, and partially restored erectile function (losartan-treated group revealed an improved intracavernous pressure/mean systemic arterial pressure ratio as compared with the diabetic group (0.480 +/- 0.031 vs. 0.329 +/- 0.020, P < 0.01). However, losartan could not elevate the reduced smooth muscle/collagen ratio in diabetic rats. The cavernous RAS plays a role in modulating erectile function in corpora cavernosa and is involved in the pathogenesis of diabetic ED. ARB can restore diabetic ED through downregulating cavernous RAS.

Endometrial Cancer Side-Population Cells Show Prominent Migration and Have a Potential to Differentiate into the Mesenchymal Cell Lineage

PubMed Central

Kato, Kiyoko; Takao, Tomoka; Kuboyama, Ayumi; Tanaka, Yoshihiro; Ohgami, Tatsuhiro; Yamaguchi, Shinichiro; Adachi, Sawako; Yoneda, Tomoko; Ueoka, Yousuke; Kato, Keiji; Hayashi, Shinichi; Asanoma, Kazuo; Wake, Norio

2010-01-01

Cancer stem-like cell subpopulations, referred to as “side-population” (SP) cells, have been identified in several tumors based on their ability to efflux the fluorescent dye Hoechst 33342. Although SP cells have been identified in the normal human endometrium and endometrial cancer, little is known about their characteristics. In this study, we isolated and characterized the SP cells in human endometrial cancer cells and in rat endometrial cells expressing oncogenic human K-Ras protein. These SP cells showed i) reduction in the expression levels of differentiation markers; ii) long-term proliferative capacity of the cell cultures; iii) self-renewal capacity in vitro; iv) enhancement of migration, lamellipodia, and, uropodia formation; and v) enhanced tumorigenicity. In nude mice, SP cells formed large, invasive tumors, which were composed of both tumor cells and stromal-like cells with enriched extracellular matrix. The expression levels of vimentin, α-smooth muscle actin, and collagen III were enhanced in SP tumors compared with the levels in non-SP tumors. In addition, analysis of microdissected samples and fluorescence in situ hybridization of Hec1-SP-tumors showed that the stromal-like cells with enriched extracellular matrix contained human DNA, confirming that the stromal-like cells were derived from the inoculated cells. Moreober, in a Matrigel assay, SP cells differentiated into α-smooth muscle actin-expressing cells. These findings demonstrate that SP cells have cancer stem-like cell features, including the potential to differentiate into the mesenchymal cell lineage. PMID:20008133

Evaluation of pier-scour equations for coarse-bed streams

USGS Publications Warehouse

Chase, Katherine J.; Holnbeck, Stephen R.

2004-01-01

Streambed scour at bridge piers is among the leading causes of bridge failure in the United States. Several pier-scour equations have been developed to calculate potential scour depths at existing and proposed bridges. Because many pier-scour equations are based on data from laboratory flumes and from cohesionless silt- and sand-bottomed streams, they tend to overestimate scour for piers in coarse-bed materials. Several equations have been developed to incorporate the mitigating effects of large particle sizes on pier scour, but further investigations are needed to evaluate how accurately pier-scour depths calculated by these equations match measured field data. This report, prepared in cooperation with the Montana Department of Transportation, describes the evaluation of five pier-scour equations for coarse-bed streams. Pier-scour and associated bridge-geometry, bed-material, and streamflow-measurement data at bridges over coarse-bed streams in Montana, Alaska, Maryland, Ohio, and Virginia were selected from the Bridge Scour Data Management System. Pier scour calculated using the Simplified Chinese equation, the Froehlich equation, the Froehlich design equation, the HEC-18/Jones equation and the HEC-18/Mueller equation for flood events with approximate recurrence intervals of less than 2 to 100 years were compared to 42 pier-scour measurements. Comparison of results showed that pier-scour depths calculated with the HEC-18/Mueller equation were seldom smaller than measured pier-scour depths. In addition, pier-scour depths calculated using the HEC-18/Mueller equation were closer to measured scour than for the other equations that did not underestimate pier scour. However, more data are needed from coarse-bed streams and from less frequent flood events to further evaluate pier-scour equations.

Bibliography of Selected SCSD, URBS, SSP, SEF, and RAS Publications.

ERIC Educational Resources Information Center

Stanford Univ., CA. School Planning Lab.

The annotated bibliography contains publications and report listings of the following sources--(1) School Construction Systems Development (SCSD), (2) University Residential Building Systems (URBS), (3) Florida Schoolhouse Systems Project (SSP), (4) Study of Educational Facilities (SEF), and (5) Recherches en Amenagements Scolaires (RAS) Building…

Development of recombinant adeno-associated virus vectors carrying small interfering RNA (shHec1)-mediated depletion of kinetochore Hec1 protein in tumor cells.

PubMed

Li, L; Yang, L; Scudiero, D A; Miller, S A; Yu, Z-X; Stukenberg, P T; Shoemaker, R H; Kotin, R M

2007-05-01

Transcript depletion using small interfering RNA (siRNA) technology represents a potentially valuable technique for the treatment of cancer. However, delivering therapeutic quantities of siRNA into solid tumors by chemical transfection is not feasible, whereas viral vectors efficiently transduce many human tumor cell lines. Yet producing sufficient quantities of viral vectors that elicit acute and selective cytotoxicity remains a major obstacle for preclinical and clinical trials. Using the invertebrate Spodoptera frugiperda (Sf9) cell line, we were able to produce high titer stocks of cytotoxic recombinant adeno-associated virus (rAAV) that express short hairpin RNA (shRNA) and that efficiently deplete Hec1 (highly expressed in cancer 1), or Kntc2 (kinetochore-associated protein 2), a kinetochore protein directly involved in kinetochore microtubule interactions, chromosome congression and spindle checkpoint signaling. Depletion of Hec1 protein results in persistent spindle checkpoint activation followed by cell death. Because Hec1 expression and activity are only present in mitotic cells, non-dividing cells were not affected by rAAV treatment. On the basis of the results of screening 56 human tumor cell lines with three different serotype vectors, we used a tumor xenograft model to test the effects in vivo. The effects of the shHec1 vector were evident in sectioned and stained tumors. The experiments with rAAV-shRNA vectors demonstrate the utility of producing vectors in invertebrate cells to obtain sufficient concentrations and quantities for solid tumor therapy. This addresses an important requirement for cancer gene therapy, to produce cytotoxic vectors in sufficient quantities and concentrations to enable quantitative transduction and selective killing of solid tumor cells.

Occurrence of putative virulence genes on Arcobacter butzleri isolated from three different environmental sites throughout the dairy chain.

PubMed

Piva, S; Gariano, G R; Bonilauri, P; Giacometti, F; Decastelli, L; Florio, D; Massella, E; Serraino, A

2017-04-01

This comparative study investigated the occurrence of cadF, cj1349, ciaB, pldA, tlyA, hecA, hecB, mviN, irgA and IroE genes in 212 Arcobacter butzleri isolated from three different environmental sites linked to the dairy chain (farms, industrial and artisanal dairy plants) located in three Italian regions (Lombardy, Emilia-Romagna and Calabria). According to the presence of these genes, different pathotypes (P-types) were determined. The main genes detected were ciaB, mviN, tlyA, cj1349, pldA and cadF, while the least common genes were iroE, hecA, hecB and irgA. TlyA, irgA, hecA, hecB and iroE, which were significantly more frequent in isolates recovered in industrial dairy plants. Twelve P-types were detected. The occurrence of the most frequently detected P-types (P-types 1, 2, 3 and 5) differed significantly (P < 0·001) in relation to both the environmental site and geographical area of isolation. The highest diversity in P-types was observed in industrial dairy plants and in the Calabria region. The results of this study show a correlation between the occurrence of putative virulence genes and virulence genotype variability depending on the environmental site and geographical origin of the isolates. The present study provides insights into the similar distribution of putative virulence genes in a dairy chain and other sources' isolates and also into a geographical distribution of some P-types. We have shown that industrial dairy plants may represent an environmental site favouring a selection of the isolates with a higher pathogenetic pattern. © 2017 The Society for Applied Microbiology.

Physical exercise enhances protein kinase C delta activity and insulin receptor tyrosine phosphorylation in diabetes-prone psammomys obesus.

PubMed

Heled, Yuval; Shapiro, Yair; Shani, Yoav; Moran, Dani S; Langzam, Leah; Braiman, Liora; Sampson, Sanford R; Meyerovitch, Joseph

2003-08-01

We recently reported that physical exercise prevents the progression of type 2 diabetes mellitus in Psammomys obesus, an animal model of nutritionally induced type 2 diabetes mellitus. In the present study we characterized the effect of physical exercise on protein kinase C delta (PKC delta) activity, as a mediator of the insulin-signaling cascade in vivo. Three groups of Psammomys obesus were exposed to a 4-week protocol: high-energy diet (HE/C), high-energy diet and exercise (HE/EX), or low-energy diet (LE/C). None of the animals in the HE/EX group became diabetic, whereas all the animals in the HE/C group became diabetic. After overnight fast, intraperitoneal (IP) insulin (1U) caused a greater reduction in blood glucose levels in the HE/EX and LE/C groups compared to the HE/C group. Tyrosine phosphorylation of insulin receptor (IR), insulin receptor substrate-1 (IRS-1), and phosphatidylinositol 3 kinase (PI3 kinase) was significantly higher in the HE/EX and LE/C groups compared with the HE/C group. Finally, IR-associated PKC delta was higher in the HE/EX and LE/C groups compared to the HE/C group. Coprecipitation of PKC delta with IR was higher in the HE/EX and LE/C groups compared to the HE/C group. Thus, we suggest that 4 weeks of physical exercise results in improved insulin-signaling response in Psammomys obesus accompanied by a direct connection between PKC delta and IR. We conclude that this mechanism may be involved in the preventive effect of exercise on type 2 diabetes mellitus in Psammomys obesus.

Breeding of a sake yeast mutant with enhanced ethyl caproate productivity in sake brewing using rice milled at a high polishing ratio.

PubMed

Takahashi, Toshinari; Ohara, Yusuke; Sueno, Kazuo

2017-06-01

Sake yeast produces a fruity flavor known as ginjo-ko-which is mainly attributable to ethyl caproate and isoamyl acetate-during fermentation in sake brewing. The production of these flavor components is inhibited by unsaturated fatty acids derived from the outer layer of rice as raw material. We isolated three mutants (hec2, hec3, and hec6) with enhanced ethyl caproate productivity in sake brewing using rice milled at a high polishing ratio from a cerulenin-resistant mutant derived from the hia1 strain, which shows enhanced isoamyl acetate productivity. The hec2 mutant had the homozygous FAS2 mutation Gly1250Ser, which is known to confer high ethyl caproate productivity. When the homozygous FAS2 mutation Gly1250Ser was introduced into strain hia1, ethyl caproate productivity was increased but neither this nor intracellular caproic acid content approached the levels observed in the hec2 mutant, indicating that a novel mutation was responsible for the high ethyl caproate productivity. We also found that the expression of EEB1 encoding acyl-coenzyme A:ethanol O-acyltransferase (AEATase) and enzymatic activity were increased in the hec2 mutant. These results suggest that the upregulation of EEB1 expression and AEATase activity may also have contributed to the enhancement of ethyl caproate synthesis from ethanol and caproyl-CoA. Our findings are useful for the brewing of sake with improved flavor due to high levels of isoamyl acetate and ethyl caproate. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

DRoP: a water analysis program identifies Ras-GTP-specific pathway of communication between membrane-interacting regions and the active site.

PubMed

Kearney, Bradley M; Johnson, Christian W; Roberts, Daniel M; Swartz, Paul; Mattos, Carla

2014-02-06

Ras GTPase mediates several cellular signal transduction pathways and is found mutated in a large number of cancers. It is active in the GTP-bound state, where it interacts with effector proteins, and at rest in the GDP-bound state. The catalytic domain is tethered to the membrane, with which it interacts in a nucleotide-dependent manner. Here we present the program Detection of Related Solvent Positions (DRoP) for crystallographic water analysis on protein surfaces and use it to study Ras. DRoP reads and superimposes multiple Protein Data Bank coordinates, transfers symmetry-related water molecules to the position closest to the protein surface, and ranks the waters according to how well conserved and tightly clustered they are in the set of structures. Coloring according to this rank allows visualization of the results. The effector-binding region of Ras is hydrated with highly conserved water molecules at the interface between the P-loop, switch I, and switch II, as well as at the Raf-RBD binding pocket. Furthermore, we discovered a new conserved water-mediated H-bonding network present in Ras-GTP, but not in Ras-GDP, that links the nucleotide sensor residues R161 and R164 on helix 5 to the active site. The double mutant RasN85A/N86A, where the final link between helix 5 and the nucleotide is not possible, is a severely impaired enzyme, while the single mutant RasN86A, with partial connection to the active site, has a wild-type hydrolysis rate. DRoP was instrumental in determining the water-mediated connectivity networks that link two lobes of the catalytic domain in Ras. Copyright © 2013 Elsevier Ltd. All rights reserved.

Chattahoochee River Water Quality Analysis.

DTIC Science & Technology

1978-04-01

in 1972 with WRE for addition of storm water quality computations. Since then the HEC has added other capabilities including snowmelt and land surface...Geological Survey. The storm water quality data were reported in reference 2. Quantity The quantity calibration involved adjusting the pervious area

Design and Evaluation of Scour for Bridges Using HEC-18 : technical brief.

DOT National Transportation Integrated Search

2017-07-01

This project developed a new approach for evaluating erosive scour at New Jersey bridges over non-tidal waterways. The main deliverable was the Scour Evaluation Model (SEM), which offers new analysis procedures, while still retaining the applicable p...

Rearing Water Treatment Induces Microbial Selection Influencing the Microbiota and Pathogen Associated Transcripts of Cod (Gadus morhua) Larvae.

PubMed

Vestrum, Ragnhild I; Attramadal, Kari J K; Winge, Per; Li, Keshuai; Olsen, Yngvar; Bones, Atle M; Vadstein, Olav; Bakke, Ingrid

2018-01-01

We have previously shown that K-selection and microbial stability in the rearing water increases survival and growth of Atlantic cod ( Gadus morhua ) larvae, and that recirculating aquaculture systems (RAS) are compatible with this. Here, we have assessed how water treatment influenced the larval microbiota and host responses at the gene expression level. Cod larvae were reared with two different rearing water systems: a RAS and a flow-through system (FTS). The water microbiota was examined using a 16S rDNA PCR/DGGE strategy. RNA extracted from larvae at 8, 13, and 17 days post hatching was used for microbiota and microarray gene expression analysis. Bacterial cDNA was synthesized and used for 16S rRNA amplicon 454 pyrosequencing of larval microbiota. Both water and larval microbiota differed significantly between the systems, and the larval microbiota appeared to become more dissimilar between systems with time. In total 4 phyla were identified for all larvae: Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria. The most profound difference in larval microbiota was a high abundance of Arcobacter (Epsilonproteobacteria) in FTS larvae (34 ± 9% of total reads). Arcobacter includes several species that are known pathogens for humans and animals. Cod larval transcriptome responses were investigated using an oligonucleotide gene expression microarray covering approximately 24,000 genes. Interestingly, FTS larvae transcriptional profiles revealed an overrepresentation of upregulated transcripts associated with responses to pathogens and infections, such as c1ql3-like , pglyrp-2-like and zg16, compared to RAS larvae. In conclusion, distinct water treatment systems induced differences in the larval microbiota. FTS larvae showed up-regulation of transcripts associated with responses to microbial stress. These results are consistent with the hypothesis that RAS promotes K-selection and microbial stability by maintaining a microbial load close to the carrying capacity of the system, and ensuring long retention times for both bacteria and water in the system.

Rearing Water Treatment Induces Microbial Selection Influencing the Microbiota and Pathogen Associated Transcripts of Cod (Gadus morhua) Larvae

PubMed Central

Vestrum, Ragnhild I.; Attramadal, Kari J. K.; Winge, Per; Li, Keshuai; Olsen, Yngvar; Bones, Atle M.; Vadstein, Olav; Bakke, Ingrid

2018-01-01

We have previously shown that K-selection and microbial stability in the rearing water increases survival and growth of Atlantic cod (Gadus morhua) larvae, and that recirculating aquaculture systems (RAS) are compatible with this. Here, we have assessed how water treatment influenced the larval microbiota and host responses at the gene expression level. Cod larvae were reared with two different rearing water systems: a RAS and a flow-through system (FTS). The water microbiota was examined using a 16S rDNA PCR/DGGE strategy. RNA extracted from larvae at 8, 13, and 17 days post hatching was used for microbiota and microarray gene expression analysis. Bacterial cDNA was synthesized and used for 16S rRNA amplicon 454 pyrosequencing of larval microbiota. Both water and larval microbiota differed significantly between the systems, and the larval microbiota appeared to become more dissimilar between systems with time. In total 4 phyla were identified for all larvae: Actinobacteria, Bacteroidetes, Firmicutes, and Proteobacteria. The most profound difference in larval microbiota was a high abundance of Arcobacter (Epsilonproteobacteria) in FTS larvae (34 ± 9% of total reads). Arcobacter includes several species that are known pathogens for humans and animals. Cod larval transcriptome responses were investigated using an oligonucleotide gene expression microarray covering approximately 24,000 genes. Interestingly, FTS larvae transcriptional profiles revealed an overrepresentation of upregulated transcripts associated with responses to pathogens and infections, such as c1ql3-like, pglyrp-2-like and zg16, compared to RAS larvae. In conclusion, distinct water treatment systems induced differences in the larval microbiota. FTS larvae showed up-regulation of transcripts associated with responses to microbial stress. These results are consistent with the hypothesis that RAS promotes K-selection and microbial stability by maintaining a microbial load close to the carrying capacity of the system, and ensuring long retention times for both bacteria and water in the system. PMID:29765364

Combination use of medicines from two classes of renin-angiotensin system blocking agents: risk of hyperkalemia, hypotension, and impaired renal function.

PubMed

Esteras, Raquel; Perez-Gomez, Maria Vanessa; Rodriguez-Osorio, Laura; Ortiz, Alberto; Fernandez-Fernandez, Beatriz

2015-08-01

European and United States regulatory agencies recently issued warnings against the use of dual renin-angiotensin system (RAS) blockade therapy through the combined use of angiotensin-converting enzyme inhibitors (ACEIs), angiotensin II receptor blockers (ARBs) or aliskiren in any patient, based on absence of benefit for most patients and increased risk of hyperkalemia, hypotension, and renal failure. Special emphasis was made not to use these combinations in patients with diabetic nephropathy. The door was left open to therapy individualization, especially for patients with heart failure, when the combined use of an ARB and ACEI is considered absolutely essential, although renal function, electrolytes and blood pressure should be closely monitored. Mineralocorticoid receptor antagonists were not affected by this warning despite increased risk of hyperkalemia. We now critically review the risks associated with dual RAS blockade and answer the following questions: What safety issues are associated with dual RAS blockade? Can the safety record of dual RAS blockade be improved? Is it worth trying to improve the safety record of dual RAS blockade based on the potential benefits of the combination? Is dual RAS blockade dead? What is the role of mineralocorticoid antagonists in combination with other RAS blocking agents: RAAS blockade?

Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis.

PubMed

Trentin, Luca; Bresolin, Silvia; Giarin, Emanuela; Bardini, Michela; Serafin, Valentina; Accordi, Benedetta; Fais, Franco; Tenca, Claudya; De Lorenzo, Paola; Valsecchi, Maria Grazia; Cazzaniga, Giovanni; Kronnie, Geertruy Te; Basso, Giuseppe

2016-10-04

To induce and sustain the leukaemogenic process, MLL-AF4+ leukaemia seems to require very few genetic alterations in addition to the fusion gene itself. Studies of infant and paediatric patients with MLL-AF4+ B cell precursor acute lymphoblastic leukaemia (BCP-ALL) have reported mutations in KRAS and NRAS with incidences ranging from 25 to 50%. Whereas previous studies employed Sanger sequencing, here we used next generation amplicon deep sequencing for in depth evaluation of RAS mutations in 36 paediatric patients at diagnosis of MLL-AF4+ leukaemia. RAS mutations including those in small sub-clones were detected in 63.9% of patients. Furthermore, the mutational analysis of 17 paired samples at diagnosis and relapse revealed complex RAS clone dynamics and showed that the mutated clones present at relapse were almost all originated from clones that were already detectable at diagnosis and survived to the initial therapy. Finally, we showed that mutated patients were indeed characterized by a RAS related signature at both transcriptional and protein levels and that the targeting of the RAS pathway could be of beneficial for treatment of MLL-AF4+ BCP-ALL clones carrying somatic RAS mutations.

DNA profiling analysis of endometrial and ovarian cell lines reveals misidentification, redundancy and contamination.

PubMed

Korch, Christopher; Spillman, Monique A; Jackson, Twila A; Jacobsen, Britta M; Murphy, Susan K; Lessey, Bruce A; Jordan, V Craig; Bradford, Andrew P

2012-10-01

Cell lines derived from human ovarian and endometrial cancers, and their immortalized non-malignant counterparts, are critical tools to investigate and characterize molecular mechanisms underlying gynecologic tumorigenesis, and facilitate development of novel therapeutics. To determine the extent of misidentification, contamination and redundancy, with evident consequences for the validity of research based upon these models, we undertook a systematic analysis and cataloging of endometrial and ovarian cell lines. Profiling of cell lines by analysis of DNA microsatellite short tandem repeats (STR), p53 nucleotide polymorphisms and microsatellite instability was performed. Fifty-one ovarian cancer lines were profiled with ten found to be redundant and five (A2008, OV2008, C13, SK-OV-4 and SK-OV-6) identified as cervical cancer cells. Ten endometrial cell lines were analyzed, with RL-92, HEC-1A, HEC-1B, HEC-50, KLE, and AN3CA all exhibiting unique, uncontaminated STR profiles. Multiple variants of Ishikawa and ECC-1 endometrial cancer cell lines were genotyped and analyzed by sequencing of mutations in the p53 gene. The profile of ECC-1 cells did not match the EnCa-101 tumor, from which it was reportedly derived, and all ECC-1 isolates were genotyped as Ishikawa cells, MCF-7 breast cancer cells, or a combination thereof. Two normal, immortalized endometrial epithelial cell lines, HES cells and the hTERT-EEC line, were identified as HeLa cervical carcinoma and MCF-7 breast cancer cells, respectively. Results demonstrate significant misidentification, duplication, and loss of integrity of endometrial and ovarian cancer cell lines. Authentication by STR DNA profiling is a simple and economical method to verify and validate studies undertaken with these models. Copyright © 2012 Elsevier Inc. All rights reserved.

Expression and Functional Significance of HtrA1 Loss in Endometrial Cancer

PubMed Central

Mullany, Sally A.; Moslemi-Kebria, Mehdi; Rattan, Ramandeep; Khurana, Ashwani; Clayton, Amy; Ota, Takayo; Mariani, Andrea; Podratz, Karl C.; Chien, Jeremy; Shridhar, Viji

2010-01-01

Purpose The purpose of this study was to determine if loss of serine protease HtrA1 in endometrial cancer will promote the invasive potential of EC cell lines. Experimental design Western blot analysis and immunohistochemistry methods were used to determine HtrA1 expression in EC cell lines and primary tumors, respectively. Migration, invasion assays and in vivo xenograft experiment were performed to compare the extent of metastasis between HtrA1 expressing and HtrA-1 knocked down clones. Results Western blot analysis of HtrA1 in 13 EC cell lines revealed complete loss of HtrA1 expression in all 7 papillary serous EC cell lines. Downregulation of HtrA1 in Hec1A and Hec1B cell lines resulted in a 3-4 fold increase in the invasive potential. Exogenous expression of HtrA1 in Ark 1 and Ark 2 cells resulted in 3-4 fold decrease in both invasive and migration potential of these cells. There was an increased rate of metastasis to the lungs associated with HtrA1 downregulation in Hec1B cells compared to control cells with endogenous HtrA1 expression. Enhanced expression of HtrA1 in Ark 2 cells resulted in significantly less tumor nodules metastasizing to the lungs compared to parental or protease deficient (SA mutant) Ark 2 cells. Immunohistochemical (IHC) analysis showed 57% (105/184) of primary EC tumors had low HtrA1 expression. The association of low HtrA1 expression with high-grade endometrioid tumors was statistically significant (p=0.016). Conclusions Collectively, these data indicate loss of HtrA1 may contribute to the aggressiveness and metastatic ability of endometrial tumors. PMID:21098697

Forecasting skills of the ensemble hydro-meteorological system for the Po river floods

NASA Astrophysics Data System (ADS)

Ricciardi, Giuseppe; Montani, Andrea; Paccagnella, Tiziana; Pecora, Silvano; Tonelli, Fabrizio

2013-04-01

The Po basin is the largest and most economically important river-basin in Italy. Extreme hydrological events, including floods, flash floods and droughts, are expected to become more severe in the next future due to climate change, and related ground effects are linked both with environmental and social resilience. A Warning Operational Center (WOC) for hydrological event management was created in Emilia Romagna region. In the last years, the WOC faced challenges in legislation, organization, technology and economics, achieving improvements in forecasting skill and information dissemination. Since 2005, an operational forecasting and modelling system for flood modelling and forecasting has been implemented, aimed at supporting and coordinating flood control and emergency management on the whole Po basin. This system, referred to as FEWSPo, has also taken care of environmental aspects of flood forecast. The FEWSPo system has reached a very high level of complexity, due to the combination of three different hydrological-hydraulic chains (HEC-HMS/RAS - MIKE11 NAM/HD, Topkapi/Sobek), with several meteorological inputs (forecasted - COSMOI2, COSMOI7, COSMO-LEPS among others - and observed). In this hydrological and meteorological ensemble the management of the relative predictive uncertainties, which have to be established and communicated to decision makers, is a debated scientific and social challenge. Real time activities face professional, modelling and technological aspects but are also strongly interrelated with organization and human aspects. The authors will report a case study using the operational flood forecast hydro-meteorological ensemble, provided by the MIKE11 chain fed by COSMO_LEPS EQPF. The basic aim of the proposed approach is to analyse limits and opportunities of the long term forecast (with a lead time ranging from 3 to 5 days), for the implementation of low cost actions, also looking for a well informed decision making and the improvement of flood preparedness and crisis management for basins greater than 1.000 km2.

Dam-breach analysis and flood-inundation mapping for Lakes Ellsworth and Lawtonka near Lawton, Oklahoma

USGS Publications Warehouse

Rendon, Samuel H.; Ashworth, Chad E.; Smith, S. Jerrod

2012-01-01

Dams provide beneficial functions such as flood control, recreation, and reliable water supplies, but they also entail risk: dam breaches and resultant floods can cause substantial property damage and loss of life. The State of Oklahoma requires each owner of a high-hazard dam, which the Federal Emergency Management Agency defines as dams for which failure or misoperation probably will cause loss of human life, to develop an emergency action plan specific to that dam. Components of an emergency action plan are to simulate a flood resulting from a possible dam breach and map the resulting downstream flood-inundation areas. The resulting flood-inundation maps can provide valuable information to city officials, emergency managers, and local residents for planning the emergency response if a dam breach occurs. Accurate topographic data are vital for developing flood-inundation maps. This report presents results of a cooperative study by the city of Lawton, Oklahoma, and the U.S. Geological Survey (USGS) to model dam-breach scenarios at Lakes Ellsworth and Lawtonka near Lawton and to map the potential flood-inundation areas of such dam breaches. To assist the city of Lawton with completion of the emergency action plans for Lakes Ellsworth and Lawtonka Dams, the USGS collected light detection and ranging (lidar) data that were used to develop a high-resolution digital elevation model and a 1-foot contour elevation map for the flood plains downstream from Lakes Ellsworth and Lawtonka. This digital elevation model and field measurements, streamflow-gaging station data (USGS streamflow-gaging station 07311000, East Cache Creek near Walters, Okla.), and hydraulic values were used as inputs for the dynamic (unsteady-flow) model, Hydrologic Engineering Center's River Analysis System (HEC-RAS). The modeled flood elevations were exported to a geographic information system to produce flood-inundation maps. Water-surface profiles were developed for a 75-percent probable maximum flood scenario and a sunny-day dam-breach scenario, as well as for maximum flood-inundation elevations and flood-wave arrival times for selected bridge crossings. Some areas of concern near the city of Lawton, if a dam breach occurs at Lakes Ellsworth or Lawtonka, include water treatment plants, wastewater treatment plants, recreational areas, and community-services offices.

[Clinical relevance of the K-ras oncogene in colorectal cancer: experience in a Mexican population].

PubMed

Cabrera-Mendoza, F; Gainza-Lagunes, S; Castañeda-Andrade, I; Castro-Zárate, A

2014-01-01

Colorectal cancer is frequent in the developed countries, with a cancer-specific mortality rate of 33%. Different biomarkers are associated with overall survival and the prediction of monoclonal treatment effectiveness. The presence of mutations in the K-ras oncogene alters the response to target therapy with cetuximab and could be an independent prognostic factor. To analyze the difference in survival between patients with mutated K-ras and those with K-ras wild-type status. Thirty-one clinical records were retrospectively analyzed of patients presenting with colorectal cancer that underwent K-ras sequencing through real-time polymerase chain reaction within the time frame of 2009 to 2012 at the Hospital de Alta Especialidad de Veracruz of the Instituto para la Salud y Seguridad Social de los Trabajadores del Estado (HAEV-ISSSTE). Survival analysis for patients with and without K-ras mutation was performed using the Kaplan Meier method. Contrast of covariates was performed using logarithmic transformations. No statistically significant difference was found in relation to survival in the patients with mutated K-ras vs. those with K-ras wild-type (P=.416), nor were significant differences found when analyzing the covariants and survival in the patients with mutated K-ras: ECOG scale (P=.221); age (less than, equal to or greater than 65years, P=.441); clinical stage according to the AJCC (P=.057), and primary lesion site (P=.614). No relation was found between the K-ras oncogene mutation and reduced survival, in contrast to what has been established in the international medical literature. Further studies that include both a larger number of patients and those receiving monoclonal treatment, need to be conducted. There were only 5 patients in the present study that received cetuximab, resulting in a misleading analysis. Copyright © 2013 Asociación Mexicana de Gastroenterología. Published by Masson Doyma México S.A. All rights reserved.

Production of cobia in recirculating systems

USDA-ARS?s Scientific Manuscript database

Only limited information exists with respect to rearing juvenile cobia Rachycentron canadum to stocker and marketable sizes using recirculating aquaculture systems (RAS). To investigate this topic, two rearing trials were conducted using commercial scale RAS. In Trial 1, juvenile cobia (29 g) we...

Freshwater Institute: Focused on improving recirculating aquaculture system technology

USDA-ARS?s Scientific Manuscript database

Recirculating aquaculture system (RAS) technologies help to overcome barriers to domestic aquaculture expansion and enhance the sustainability of the modern fish farming industry through reduction in environmental impacts. With RAS, fish farm expansion is no longer highly constrained by competition ...

TAN-1813, a novel Ras-farnesyltransferase inhibitor produced by Phoma sp. taxonomy, fermentation, isolation and biological activities in vitro and in vivo.

PubMed

Ishii, T; Hayashi, K; Hida, T; Yamamoto, Y; Nozaki, Y

2000-08-01

A novel Ras-farnesyltransferase inhibitor designated TAN-1813 was isolated from the culture broth of a fungus strain, FL-41510, isolated as a plant endophyte. The producer was taxonomically characterized as Phoma sp. FL-41510. TAN-1813 inhibited rat brain farnesyltransferase and geranylgeranyltransferase I activity with IC50 values of 23 microg/ml and 47/microg/ml, respectively. TAN-1813 showed mixed-type inhibition with respect to farnesylpyrophosphate and noncompetitive inhibition with respect to a K-Ras C-terminal peptide. It also inhibited the in situ farnesylation of cellular Ras proteins in a K-ras transformant (NIH3T3/K-ras) of mouse embryonic fibroblast cell line NIH3T3. TAN- 1813 inhibited the proliferation of various human cancer cells, some of which harbor activated ras alleles, with IC50 values of 15 approximately 110 ng/ml as well as that of NIH3T3 and NIH3T3/K-ras cells with IC50S of 540 and 310 ng/ml, respectively. Flow cytometric analysis indicated that TAN-1813 arrests NIH3T3/K-ras cells at both G1 and G2/M phases of the cell cycle. In addition, TAN-1813 was found to induce morphological reversion of NIH3T3/K-ras cells from the transformed phenotype. Antitumor activity of TAN-1813 against human fibrosarcoma HT-1080 and NIH3T3/K-ras tumors in nude mice was also verified.

Analysis of Binding Site Hot Spots on the Surface of Ras GTPase

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

Buhrman, Greg; O; #8242

2012-09-17

We have recently discovered an allosteric switch in Ras, bringing an additional level of complexity to this GTPase whose mutants are involved in nearly 30% of cancers. Upon activation of the allosteric switch, there is a shift in helix 3/loop 7 associated with a disorder to order transition in the active site. Here, we use a combination of multiple solvent crystal structures and computational solvent mapping (FTMap) to determine binding site hot spots in the 'off' and 'on' allosteric states of the GTP-bound form of H-Ras. Thirteen sites are revealed, expanding possible target sites for ligand binding well beyond themore » active site. Comparison of FTMaps for the H and K isoforms reveals essentially identical hot spots. Furthermore, using NMR measurements of spin relaxation, we determined that K-Ras exhibits global conformational dynamics very similar to those we previously reported for H-Ras. We thus hypothesize that the global conformational rearrangement serves as a mechanism for allosteric coupling between the effector interface and remote hot spots in all Ras isoforms. At least with respect to the binding sites involving the G domain, H-Ras is an excellent model for K-Ras and probably N-Ras as well. Ras has so far been elusive as a target for drug design. The present work identifies various unexplored hot spots throughout the entire surface of Ras, extending the focus from the disordered active site to well-ordered locations that should be easier to target.« less

RAS and sex differences in diabetic nephropathy.

PubMed

Clotet, Sergi; Riera, Marta; Pascual, Julio; Soler, Maria José

2016-03-09

The incidence and progression of kidney diseases are influenced by sex. The renin-angiotensin system (RAS) is an important regulator of cardiovascular and renal function. Sex differences in the renal response to RAS blockade have been demonstrated. Circulating and renal RAS has been shown to be altered in type 1 and type 2 diabetes; this enzymatic cascade plays a critical role in the development of diabetic nephropathy (DN). Angiotensin converting enzyme (ACE) and ACE2 are differentially regulated depending on its localization within the diabetic kidney. Furthermore, clinical and experimental studies have shown that circulating levels of sex hormones are clearly modulated in the context of diabetes, suggesting that sex-dependent RAS regulation may be also be affected in these individuals. The effect of sex hormones on circulating and renal RAS may be involved in the sex differences observed in DN progression. In this paper we will review the influence of sex hormones on RAS expression and its relation to diabetic kidney disease. A better understanding of the sex dimorphism on RAS might provide a new approach for diabetic kidney disease treatment. Copyright © 2015, American Journal of Physiology - Renal Physiology.

77 FR 56581 - Airworthiness Directives; Sikorsky Aircraft Corporation Helicopters

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-13

... HEC, in this model helicopter that now meets the Category A performance standard. DATES: We must... airworthiness directive (AD) for the Sikorsky Aircraft Corporation (Sikorsky) Model S-92A helicopter, which... external load operations, including human external cargo (HEC), because this model helicopter was not...

NEPA, a new fixed combination of netupitant and palonosetron, is a cost-effective intervention for the prevention of chemotherapy-induced nausea and vomiting in the UK

PubMed Central

Cawston, Helene; Bourhis, Francois; Eriksson, Jennifer; Ruffo, Pierfrancesco; D’Agostino, Paolo; Turini, Marco; Schwartzberg, Lee; McGuire, Alistair

2017-01-01

Background The objective was to evaluate the cost-effectiveness of NEPA, an oral fixed combination netupitant (NETU, 300 mg) and palonosetron (PA, 0.5 mg) compared with aprepitant and palonosetron (APPA) or palonosetron (PA) alone, to prevent chemotherapy-induced nausea and vomiting (CINV) in patients undergoing treatment with highly or moderately emetogenic chemotherapy (HEC or MEC) in the UK. Scope A systematic literature review and meta-analysis were undertaken to compare NEPA with currently recommended anti-emetics. Relative effectiveness was estimated over the acute (day 1) and overall treatment (days 1–5) phases, taking complete response (CR, no emesis and no rescue medication) and complete protection (CP, CR and no more than mild nausea [VAS scale <25 mm]) as primary efficacy outcomes. A three-health-state Markov cohort model, including CP, CR and incomplete response (no CR) for HEC and MEC, was constructed. A five-day time horizon and UK NHS perspective were adopted. Transition probabilities were obtained by combining the response rates of CR and CP from NEPA trials and odds ratios from the meta-analysis. Utilities of 0.90, 0.70 and 0.24 were defined for CP, CR and incomplete response, respectively. Costs included medications and management of CINV-related events and were obtained from the British National Formulary and NHS Reference Costs. The expected budgetary impact of NEPA was also evaluated. Findings In HEC patients, the NEPA strategy was more effective than APPA (quality-adjusted life days [QALDs] of 4.263 versus 4.053; incremental emesis-free and CINV-free days of +0.354 and +0.237, respectively) and was less costly (£80 versus £124), resulting in NEPA being the dominant strategy. In MEC patients, NEPA was cost effective, cumulating in an estimated 0.182 extra QALDs at an incremental cost of £6.65 compared with PA. Conclusion Despite study limitations (study setting, time horizon, utility measure), the results suggest NEPA is cost effective for preventing CINV associated with HEC and MEC in the UK. PMID:28392826

Head-to-head comparison of H2-receptor antagonists and proton pump inhibitors in the treatment of erosive esophagitis: A meta-analysis

PubMed Central

Wang, Wei-Hong; Huang, Jia-Qing; Zheng, Ge-Fan; Xia, Harry Hua-Xiang; Wong, Wai-Man; Lam, Shiu-Kum; Wong, Benjamin Chun-Yu

2005-01-01

AIM: To systematically evaluate the efficacy of H2-receptor antagonists (H2RAs) and proton pump inhibitors in healing erosive esophagitis (EE). METHODS: A meta-analysis was performed. A literature search was conducted in PubMed, Medline, Embase, and Cochrane databases to include randomized controlled head-to-head comparative trials evaluating the efficacy of H2RAs or proton pump inhibitors in healing EE. Relative risk (RR) and 95% confidence interval (CI) were calculated under a random-effects model. RESULTS: RRs of cumulative healing rates for each comparison at 8 wk were: high dose vs standard dose H2RAs, 1.17 (95%CI, 1.02-1.33); standard dose proton pump inhibitors vs standard dose H2RAs, 1.59 (95%CI, 1.44-1.75); standard dose other proton pump inhibitors vs standard dose omeprazole, 1.06 (95%CI, 0.98-1.06). Proton pump inhibitors produced consistently greater healing rates than H2RAs of all doses across all grades of esophagitis, including patients refractory to H2RAs. Healing rates achieved with standard dose omeprazole were similar to those with other proton pump inhibitors in all grades of esophagitis. CONCLUSION: H2RAs are less effective for treating patients with erosive esophagitis, especially in those with severe forms of esophagitis. Standard dose proton pump inhibitors are significantly more effective than H2RAs in healing esophagitis of all grades. Proton pump inhibitors given at the recommended dose are equally effective for healing esophagitis. PMID:15996033

Angiotensins in Alzheimer's disease - friend or foe?

PubMed

Kehoe, Patrick G; Miners, Scott; Love, Seth

2009-12-01

The renin-angiotensin system (RAS) is an important regulator of blood pressure. Observational and experimental studies suggest that alterations in blood pressure and components of the brain RAS contribute to the development and progression of Alzheimer's disease (AD), resulting in changes that can lead or contribute to cognitive decline. The complexity of the RAS and diversity of its interactions with neurological processes have recently become apparent but large gaps in our understanding still remain. Modulation of activity of components of the brain RAS offers substantial opportunities for the treatment and prevention of dementia, including AD. This paper reviews molecular, genetic, experimental and clinical data as well as the therapeutic opportunities that relate to the involvement of the RAS in AD.

Ras-Induced Changes in H3K27me3 Occur after Those in Transcriptional Activity

PubMed Central

Hosogane, Masaki; Funayama, Ryo; Nishida, Yuichiro; Nagashima, Takeshi; Nakayama, Keiko

2013-01-01

Oncogenic signaling pathways regulate gene expression in part through epigenetic modification of chromatin including DNA methylation and histone modification. Trimethylation of histone H3 at lysine-27 (H3K27), which correlates with transcriptional repression, is regulated by an oncogenic form of the small GTPase Ras. Although accumulation of trimethylated H3K27 (H3K27me3) has been implicated in transcriptional regulation, it remains unclear whether Ras-induced changes in H3K27me3 are a trigger for or a consequence of changes in transcriptional activity. We have now examined the relation between H3K27 trimethylation and transcriptional regulation by Ras. Genome-wide analysis of H3K27me3 distribution and transcription at various times after expression of oncogenic Ras in mouse NIH 3T3 cells identified 115 genes for which H3K27me3 level at the gene body and transcription were both regulated by Ras. Similarly, 196 genes showed Ras-induced changes in transcription and H3K27me3 level in the region around the transcription start site. The Ras-induced changes in transcription occurred before those in H3K27me3 at the genome-wide level, a finding that was validated by analysis of individual genes. Depletion of H3K27me3 either before or after activation of Ras signaling did not affect the transcriptional regulation of these genes. Furthermore, given that H3K27me3 enrichment was dependent on Ras signaling, neither it nor transcriptional repression was maintained after inactivation of such signaling. Unexpectedly, we detected unannotated transcripts derived from intergenic regions at which the H3K27me3 level is regulated by Ras, with the changes in transcript abundance again preceding those in H3K27me3. Our results thus indicate that changes in H3K27me3 level in the gene body or in the region around the transcription start site are not a trigger for, but rather a consequence of, changes in transcriptional activity. PMID:24009517

A Principal Components Analysis of the Rathus Assertiveness Schedule.

ERIC Educational Resources Information Center

Law, H. G.; And Others

1979-01-01

Investigated the adequacy of the Rathus Assertiveness Schedule (RAS) as a global measure of assertiveness. Analysis indicated that the RAS does not provide a unidimensional index of assertiveness, but rather measures a number of factors including situation-specific assertive behavior, aggressiveness, and a more general assertiveness. (Author)

Clay Nanoparticles Elicit Long-Term Immune Responses by Forming Biodegradable Depots for Sustained Antigen Stimulation.

PubMed

Chen, Weiyu; Zuo, Huali; Li, Bei; Duan, Chengcheng; Rolfe, Barbara; Zhang, Bing; Mahony, Timothy J; Xu, Zhi Ping

2018-05-01

Nanomaterials have been widely tested as new generation vaccine adjuvants, but few evoke efficient immunoreactions. Clay nanoparticles, for example, layered double hydroxide (LDH) and hectorite (HEC) nanoparticles, have shown their potent adjuvanticity in generating effective and durable immune responses. However, the mechanism by which clay nanoadjuvants stimulate the immune system is not well understood. Here, it is demonstrated that LDH and HEC-antigen complexes form loose agglomerates in culture medium/serum. They also form nodules with loose structures in tissue after subcutaneous injection, where they act as a depot for up to 35 d. More importantly, clay nanoparticles actively and continuously recruit immune cells into the depot for up to one month, and stimulate stronger immune responses than FDA-approved adjuvants, Alum and QuilA. Sustained antigen release is also observed in clay nanoparticle depots, with 50-60% antigen released after 35 d. In contrast, Alum-antigen complexes show minimal antigen release from the depot. Importantly, LDH and HEC are more effective than QuilA and Alum in promoting memory T-cell proliferation. These findings suggest that both clay nanoadjuvants can serve as active vaccine platforms for sustained and potent immune responses. © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Association of IL-6-174 G/C and IL10-1082 G/A polymorphisms with recurrent aphthous stomatitis risk: A meta-analysis.

PubMed

Yang, Shuo; Zhang, Bin; Shi, Quan; Liu, Jinglong; Xu, Juan; Huo, Na

2017-12-01

Recurrent aphthous stomatitis (RAS) is a common oral disease with unknown etiology. The association between IL-6-174 G/C and IL10-1082 G/A polymorphisms and the risk of RAS remains controversial. Therefore, we conducted this meta-analysis to gain more evidence-based information. Four online databases, PubMed, Embase, Web of Science, and Cochrane Library, were searched, and the relevant publications were collected. An odds ratio (OR) with a 95% confidence interval (CI) was applied to assess the association of the IL-6-174 G/C and IL10-1082 G/A polymorphisms with RAS susceptibility. Nine published case-control studies with 779 patients and 1016 controls were collected. The overall analysis proved that the IL10-1082 G/A polymorphism was significantly associated with the risk of RAS in a dominant model (GG + AG vs AA: OR = 1.49, 95% CI = 1.10-2.01, P = .01). A subgroup analysis based on ethnicity revealed significant associations in Asian populations in allelic, heterozygote, and dominant models (G vs A: OR = 1.55, 95% CI = 1.04-2.31, P = .03; AG vs AA: OR = 1.76, 95% CI = 1.16-2.67, P = .01; GG + AG vs AA: OR = 2.04, 95% CI = 1.37-3.03, P = .00). The association in Caucasians and people of mixed ethnicity requires further study. No significant association was detected between the IL-6-174 G/C polymorphism and RAS in any of the genetic models. However, subgroup analysis by ethnicity revealed that the Caucasians were more likely to develop RAS in 4 genetic models (G vs C: OR = 2.36, 95% CI = 1.26-4.41, P = .01; GG vs CC: OR = 7.05, 95% CI = 3.50-14.18, P = .00; GG + CG vs CC: OR = 4.28, 95% CI = 2.17-8.45, P = .00; GG vs CG + CC: OR = 2.59, 95% CI = 1.05-6.41, P = .04). In addition, a significantly decreased risk of RAS susceptibility was found in Asians (CG vs CC: OR = 0.27, 95% CI = 0.07-0.99, P = .049; GG + CG vs CC: OR = 0.27, 95% CI = 0.07-0.98, P = .047). Our meta-analysis indicated that the IL10-1082 G/A polymorphism is associated with RAS susceptibility, especially in Asians. In contrast, the IL-6-174 G/C polymorphism does not have a statistically significant association with RAS susceptibility. However, it may play a different role during the development of RAS in different ethnicities. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

Association between renin-angiotensin system antagonist use and mortality in heart failure with severe renal insufficiency: a prospective propensity score-matched cohort study.

PubMed

Edner, Magnus; Benson, Lina; Dahlström, Ulf; Lund, Lars H

2015-09-07

In heart failure (HF) with reduced ejection fraction (EF), renin-angiotensin receptor (RAS) antagonists reduce mortality. However, severe renal insufficiency was an exclusion criterion in trials. We tested the hypothesis that RAS antagonists are associated with reduced mortality also in HF with severe renal insufficiency. We studied patients with EF ≤39% registered in the prospective Swedish Heart Failure Registry. In patients with creatinine >221 µmol/L or creatinine clearance <30 mL/min, propensity scores for RAS-antagonist use were derived from 36 variables. The association between RAS antagonist use and all-cause mortality was assessed with Cox regression in a cohort matched 1:1 based on age and propensity score. To assess consistency, we performed the same analysis as a 'positive control' in patients without severe renal insufficiency. Between 2000 and 2013, there were 24 283 patients of which 2410 [age, mean (SD), 82 (9), 45% women] had creatinine >221 µmol/L or creatinine clearance <30 mL/min and were treated (n = 1602) or not treated (n = 808) with RAS antagonists. In the matched cohort of 602 vs. 602 patients [age 83 (8), 42% women], RAS antagonist use was associated with 55% [95% confidence interval (CI) 51-59] vs. 45% (41-49) 1-year survival, P < 0.001, with a hazard ratio (HR) for mortality of 0.76 (95% CI 0.67-0.86, P < 0.001). In positive control patients without severe renal insufficiency [n = 21 873; age 71 (12), 27% women], the matched HR was 0.79 (95% CI 0.72-0.86, P < 0.001). In HF with severe renal insufficiency, the use of RAS antagonists was associated with lower all-cause mortality. Prospective randomized trials are needed before these findings can be applied to clinical practice. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.

Lin28-let7 Modulates Radiosensitivity of Human Cancer Cells With Activation of K-Ras

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

Oh, Jee-Sun.; Kim, Jae-Jin; Byun, Ju-Yeon

2010-01-15

Purpose: To evaluate the potential of targeting Lin28-let7 microRNA regulatory network for overcoming the radioresistance of cancer cells having activated K-Ras signaling. Methods and Materials: A549 lung carcinoma cells and ASPC1 pancreatic cancer cells possessing K-RAS mutation were transfected with pre-let7a microRNA or Lin28 siRNA, respectively. Clonogenic assay, quantitative reverse transcription polymerase chain reaction, and Western analysis were performed. The effects of Lin28 on SQ20B cells having wild-type K-RAS, and a normal fibroblast were also assessed. Results: The overexpression of let-7a decreased expression of K-Ras and radiosensitized A549 cells. Inhibition of Lin28, a repressor of let-7, attenuated K-Ras expression andmore » radiosensitized A549 and ASPC1 cells. Neither SQ20B cells expressing wild-type K-RAS nor HDF, the normal human fibroblasts, were radiosensitized by this approach. Conclusions: The Lin28-let7 regulatory network may be a potentially useful therapeutic target for overcoming the radioresistance of human cancers having activated K-Ras signaling.« less

K-Ras(G12D)-selective inhibitory peptides generated by random peptide T7 phage display technology

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

Sakamoto, Kotaro; Kamada, Yusuke; Sameshima, Tomoya

Amino-acid mutations of Gly{sup 12} (e.g. G12D, G12V, G12C) of V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-Ras), the most promising drug target in cancer therapy, are major growth drivers in various cancers. Although over 30 years have passed since the discovery of these mutations in most cancer patients, effective mutated K-Ras inhibitors have not been marketed. Here, we report novel and selective inhibitory peptides to K-Ras(G12D). We screened random peptide libraries displayed on T7 phage against purified recombinant K-Ras(G12D), with thorough subtraction of phages bound to wild-type K-Ras, and obtained KRpep-2 (Ac-RRCPLYISYDPVCRR-NH{sub 2}) as a consensus sequence. KRpep-2 showedmore » more than 10-fold binding- and inhibition-selectivity to K-Ras(G12D), both in SPR analysis and GDP/GTP exchange enzyme assay. K{sub D} and IC{sub 50} values were 51 and 8.9 nM, respectively. After subsequent sequence optimization, we successfully generated KRpep-2d (Ac-RRRRCPLYISYDPVCRRRR-NH{sub 2}) that inhibited enzyme activity of K-Ras(G12D) with IC{sub 50} = 1.6 nM and significantly suppressed ERK-phosphorylation, downstream of K-Ras(G12D), along with A427 cancer cell proliferation at 30 μM peptide concentration. To our knowledge, this is the first report of a K-Ras(G12D)-selective inhibitor, contributing to the development and study of K-Ras(G12D)-targeting drugs. - Highlights: • The first K-Ras(G12D)-selective inhibitory peptides were generated. • These peptides showed more than 10-fold binding- and inhibition-selectivity to K-Ras(G12D) in compared to wild type K-Ras. • The peptide KRpep-2d suppressed downstream signal of K-Ras(G12D) and cell proliferations of cancer cell line A427.« less

Pharmacodynamic effects of C-domain-specific ACE inhibitors on the renin-angiotensin system in myocardial infarcted rats.

PubMed

Sharp, Sarah; Poglitsch, Marko; Zilla, Peter; Davies, Neil H; Sturrock, Edward D

2015-12-01

The renin-angiotensin system (RAS) is a dynamic network that plays a critical role in blood pressure regulation and fluid and electrolyte homeostasis. Modulators of the RAS, such as angiotensin-converting enzyme (ACE) inhibitors, are widely used to treat hypertension, heart failure and myocardial infarction. The effect of ACE inhibitors (lisinopril and C-domain-selective LisW-S) on the constituent peptides of the RAS following myocardial infarction was examined in rats. Ten angiotensin peptides were analysed using a sensitive LC-MS/MS-based assay to examine both the circulating and equilibrium levels of these peptides. Administration of lisinopril or LisW-S caused a significant decrease in Ang 1-8/Ang 1-10 ratios as determined by circulating and equilibrium peptide level analysis. Furthermore, Ang 1-7 levels were elevated by both ACE inhibitors, but only lisinopril decreased the Ang 1-5/Ang 1-7 ratio. This indicates LisW-S C-domain specificity as Ang 1-5 is generated by hydrolysis of Ang 1-7 by the N-domain. Further corroboration of LisW-S C-domain specificity is that only lisinopril increased the circulating levels of the N-domain ACE substrate Ac-SDKP. LisW-S is able to effectively block ACE in vivo by C-domain-selective inhibition. The LC-MS/MS-based assay allows the evaluation of the pharmacologic impact of RAS inhibitors in different pathophysiological conditions. © The Author(s) 2015.

Erythropoietin during hypoglycaemia in type 1 diabetes: relation to basal renin-angiotensin system activity and cognitive function.

PubMed

Kristensen, Peter Lommer; Høi-Hansen, Thomas; Olsen, Niels Vidiendal; Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

2009-07-01

Preservation of cognitive function during hypoglycaemic episodes is crucial for patients with insulin-treated diabetes to avoid severe hypoglycaemic events. Erythropoietin has neuroprotective potential. However, the role of erythropoietin during hypoglycaemia is unclear. The aim of the study was to explore plasma erythropoietin response to hypoglycaemia and the relationship to basal renin-angiotensin system (RAS) activity and cognitive function. We performed a single-blinded, controlled, cross-over study with induced hypoglycaemia or maintained glycaemic level. Nine patients with type 1 diabetes with high and nine with low activity in RAS were studied. Hypoglycaemia was induced using a standardized insulin-infusion. Overall, erythropoietin concentrations increased during hypoglycaemia. In the high RAS group erythropoietin rose 29% (p=0.032) whereas no significant response was observed in the low RAS group (7% increment; p=0.43). Independently, both hypoglycaemia and high RAS activity were associated with higher levels of erythropoietin (p=0.02 and 0.04, respectively). Low plasma erythropoietin at baseline was associated with poorer cognitive performance during hypoglycaemia. Hypoglycaemia triggers a rise in plasma erythropoietin in patients with type 1 diabetes. The response is influenced by basal RAS activity. Erythropoietin may carry a neuroprotective potential during hypoglycaemia.

No evidence for a local renin-angiotensin system in liver mitochondria

PubMed Central

Astin, Ronan; Bentham, Robert; Djafarzadeh, Siamak; Horscroft, James A.; Kuc, Rhoda E.; Leung, Po Sing; Skipworth, James R. A.; Vicencio, Jose M.; Davenport, Anthony P.; Murray, Andrew J.; Takala, Jukka; Jakob, Stephan M.; Montgomery, Hugh; Szabadkai, Gyorgy

2013-01-01

The circulating, endocrine renin-angiotensin system (RAS) is important to circulatory homeostasis, while ubiquitous tissue and cellular RAS play diverse roles, including metabolic regulation. Indeed, inhibition of RAS is associated with improved cellular oxidative capacity. Recently it has been suggested that an intra-mitochondrial RAS directly impacts on metabolism. Here we sought to rigorously explore this hypothesis. Radiolabelled ligand-binding and unbiased proteomic approaches were applied to purified mitochondrial sub-fractions from rat liver, and the impact of AngII on mitochondrial function assessed. Whilst high-affinity AngII binding sites were found in the mitochondria-associated membrane (MAM) fraction, no RAS components could be detected in purified mitochondria. Moreover, AngII had no effect on the function of isolated mitochondria at physiologically relevant concentrations. We thus found no evidence of endogenous mitochondrial AngII production, and conclude that the effects of AngII on cellular energy metabolism are not mediated through its direct binding to mitochondrial targets. PMID:23959064

Microarray pathway analysis indicated that mitogen-activated protein kinase/extracellular signal-regulated kinase and insulin growth factor 1 signaling pathways were inhibited by small interfering RNA against AT-rich interactive domain 1A in endometrial cancer

PubMed Central

Yang, Ye; Bao, Wei; Sang, Zhengyu; Yang, Yongbing; Lu, Meng; Xi, Xiaowei

2018-01-01

Mutations in the gene encoding AT-rich interactive domain 1A (ARID1A) are frequently observed in endometrial cancer (EC) but the molecular mechanisms linking the genetic changes remain to be fully understood. The present study aimed to elucidate the influence of ARID1A mutations on signaling pathways. Missense, synonymous and nonsense heterozygous ARID1A mutations in the EC HEC-1-A cell line were verified by Sanger sequencing. Mutated ARID1A small interfering RNA was transfected into HEC-1-A cells. Biochemical microarray analysis revealed 13 upregulated pathways, 17 downregulated pathways, 14 significantly affected disease states and functions, 662 upstream and 512 downstream genes in mutated ARID1A-depleted HEC-1-A cells, among which the mitogen-activated protein kinase/extracellular signal-regulated kinase and insulin-like growth factor-1 (IGF1) signaling pathways were the 2 most downregulated pathways. Furthermore, the forkhead box protein O1 pathway was upregulated, while the IGF1 receptor, insulin receptor substrate 1 and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit b pathways were downregulated. Carcinoma tumorigenesis, tumor cell mitosis and tumor cell death were significantly upregulated disease states and functions, while cell proliferation and tumor growth were significantly downregulated. The results of the present study suggested that ARID1A may be a potential prognostic and therapeutic molecular drug target for the prevention of EC progression. PMID:29399196

RAS mutations predict radiologic and pathologic response in patients treated with chemotherapy prior to resection of colorectal liver metastases

PubMed Central

Mise, Yoshihiro; Kopetz, Scott; Loyer, Evelyne M.; Andreou, Andreas; Cooper, Amanda B.; Kaur, Harmeet; Aloia, Thomas A.; Maru, Dipen M.; Vauthey, Jean-Nicolas

2014-01-01

Purpose RAS mutations have been reported to be a potential prognostic factor in patients with colorectal liver metastases (CLM). However, the impact of RAS mutations on response to chemotherapy remains unclear. We sought to determine the association between RAS mutations and response to preoperative chemotherapy and their impact on survival in patients undergoing curative resection of CLM. Methods RAS mutational status was assessed and its relation to morphologic response and pathologic response was investigated in 184 patients meeting inclusion criteria. Predictors of survival were assessed. The prognostic impact of RAS mutational status was then analyzed using two different multivariate models including either radiologic morphologic response (model 1) or pathologic response (model 2). Results Optimal morphologic response and major pathologic response were more common in patients with wild-type RAS (32.9% and 58.9%, respectively) than in patients with RAS mutations (10.5% and 36.8%; P =.006 and .015, respectively). Multivariate analysis confirmed that wild-type RAS was a strong predictor of optimal morphologic response (odds ratio [OR], 4.38; 95% CI, 1.45-13.2) and major pathologic response (OR,2.79; 95% CI, 1.29-6.04). RAS mutations were independently correlated with both overall survival and recurrence free-survival (hazard ratios, 3.25 and 2.02, respectively, in model 1, and 3.19 and 2.23, respectively, in model 2). Subanalysis revealed that RAS mutational status clearly stratified prognosis in patients with inadequate response to preoperative chemotherapy. Conclusion RAS mutational status can be used to complement the current prognostic indicators for patients undergoing curative resection of CLM after preoperative modern chemotherapy. PMID:25227306

RAS mutations predict radiologic and pathologic response in patients treated with chemotherapy before resection of colorectal liver metastases.

PubMed

Zimmitti, Giuseppe; Shindoh, Junichi; Mise, Yoshihiro; Kopetz, Scott; Loyer, Evelyne M; Andreou, Andreas; Cooper, Amanda B; Kaur, Harmeet; Aloia, Thomas A; Maru, Dipen M; Vauthey, Jean-Nicolas

2015-03-01

RAS mutations have been reported to be a potential prognostic factor in patients with colorectal liver metastases (CLM). However, the impact of RAS mutations on response to chemotherapy remains unclear. The purpose of this study was to investigate the correlation between RAS mutations and response to preoperative chemotherapy and their impact on survival in patients undergoing curative resection of CLM. RAS mutational status was assessed and its relation to morphologic response and pathologic response was investigated in 184 patients meeting inclusion criteria. Predictors of survival were assessed. The prognostic impact of RAS mutational status was then analyzed using two different multivariate models, including either radiologic morphologic response (model 1) or pathologic response (model 2). Optimal morphologic response and major pathologic response were more common in patients with wild-type RAS (32.9 and 58.9%, respectively) than in patients with RAS mutations (10.5 and 36.8%; P = 0.006 and 0.015, respectively). Multivariate analysis confirmed that wild-type RAS was a strong predictor of optimal morphologic response [odds ratio (OR), 4.38; 95% CI 1.45-13.15] and major pathologic response (OR, 2.61; 95% CI 1.17-5.80). RAS mutations were independently correlated with both overall survival and recurrence free-survival (hazard ratios, 3.57 and 2.30, respectively, in model 1, and 3.19 and 2.09, respectively, in model 2). Subanalysis revealed that RAS mutational status clearly stratified survival in patients with inadequate response to preoperative chemotherapy. RAS mutational status can be used to complement the current prognostic indicators for patients undergoing curative resection of CLM after preoperative modern chemotherapy.

K-Ras(G12D)-selective inhibitory peptides generated by random peptide T7 phage display technology.

PubMed

Sakamoto, Kotaro; Kamada, Yusuke; Sameshima, Tomoya; Yaguchi, Masahiro; Niida, Ayumu; Sasaki, Shigekazu; Miwa, Masanori; Ohkubo, Shoichi; Sakamoto, Jun-Ichi; Kamaura, Masahiro; Cho, Nobuo; Tani, Akiyoshi

2017-03-11

Amino-acid mutations of Gly 12 (e.g. G12D, G12V, G12C) of V-Ki-ras2 Kirsten rat sarcoma viral oncogene homolog (K-Ras), the most promising drug target in cancer therapy, are major growth drivers in various cancers. Although over 30 years have passed since the discovery of these mutations in most cancer patients, effective mutated K-Ras inhibitors have not been marketed. Here, we report novel and selective inhibitory peptides to K-Ras(G12D). We screened random peptide libraries displayed on T7 phage against purified recombinant K-Ras(G12D), with thorough subtraction of phages bound to wild-type K-Ras, and obtained KRpep-2 (Ac-RRCPLYISYDPVCRR-NH 2 ) as a consensus sequence. KRpep-2 showed more than 10-fold binding- and inhibition-selectivity to K-Ras(G12D), both in SPR analysis and GDP/GTP exchange enzyme assay. K D and IC 50 values were 51 and 8.9 nM, respectively. After subsequent sequence optimization, we successfully generated KRpep-2d (Ac-RRRRCPLYISYDPVCRRRR-NH 2 ) that inhibited enzyme activity of K-Ras(G12D) with IC 50  = 1.6 nM and significantly suppressed ERK-phosphorylation, downstream of K-Ras(G12D), along with A427 cancer cell proliferation at 30 μM peptide concentration. To our knowledge, this is the first report of a K-Ras(G12D)-selective inhibitor, contributing to the development and study of K-Ras(G12D)-targeting drugs. Copyright © 2017 Elsevier Inc. All rights reserved.

Factors determining electrostatic fields in molecular dynamics simulations of the Ras/effector interface.

PubMed

Ensign, Daniel L; Webb, Lauren J

2011-12-01

Using molecular dynamics simulations, we explore geometric and physical factors contributing to calculated electrostatic fields at the binding surface of the GTPase Ras with a spectroscopically labeled variant of a downstream effector, the Ras-binding domain of Ral guanine nucleotide dissociation stimulator (RalGDS). A related system (differing by mutation of one amino acid) has been studied in our group using vibrational Stark effect spectroscopy, a technique sensitive to electrostatic fields. Electrostatic fields were computed using the AMBER 2003 force field and averaged over snapshots from molecular dynamics simulation. We investigate geometric factors by exploring how the orientation of the spectroscopic probe changes on Ras-effector binding. In addition, we explore the physical origin of electrostatic fields at our spectroscopic probe by comparing contributions to the field from discrete components of the system, such as explicit solvent, residues on the Ras surface, and residues on the RalGDS surface. These models support our experimental hypothesis that vibrational Stark shifts are caused by Ras binding to its effector and not the structural rearrangements of the effector surface or probe reorientation on Ras-effector binding, for at least some of our experimental probes. These calculations provide physical insight into the origin, magnitude, and importance of electrostatic fields in protein-protein interactions and suggest new experiments to probe the field's role in protein docking. Copyright © 2011 Wiley-Liss, Inc.

Renin-angiotensin system blockers regulate the metabolism of isolated fat cells in vitro

PubMed Central

Caminhotto, R de O.; Sertié, R.A.L.; Andreotti, S.; Campaãa, A.B.; Lima, F.B.

2016-01-01

Due to the presence of the renin-angiotensin system (RAS) in tissues and its specific influence on white adipose tissue, fat cells are possible targets of pharmacological RAS blockers commonly used as anti-hypertensive drugs. In the present study, we investigated the effects of different RAS blockers on fat cell metabolism, more specifically on lipolysis, lipogenesis and oxidation of energy substrates. Isolated primary adipocytes were incubated with different RAS blockers (aliskiren, captopril and losartan) in vitro for 24 h and lipolysis, lipogenesis and glucose oxidation capacities were determined in dose-response assays to a β-adrenergic agonist and to insulin. Although no change was found in lipolytic capacity, the RAS blockers modulated lipogenesis and glucose oxidation in a different way. While captopril decreased insulin-stimulated lipogenesis (−19% of maximal response and −60% of insulin responsiveness) due to reduced glucose derived glycerol synthesis (−19% of maximal response and 64% of insulin responsiveness), aliskiren increased insulin-stimulated glucose oxidation (+49% of maximal response and +292% of insulin responsiveness) in fat cells. Our experiments demonstrate that RAS blockers can differentially induce metabolic alterations in adipocyte metabolism, characterized by a reduction in lipogenic responsiveness or an increase in glucose oxidation. The impact of RAS blockers on adipocyte metabolism may have beneficial implications on metabolic disorders during their therapeutic use in hypertensive patients. PMID:27487419

The Association Between Renin-Angiotensin System Blockade and Long-term Outcomes in Renal Transplant Recipients: The Wisconsin Allograft Recipient Database (WisARD).

PubMed

Shin, Jung-Im; Palta, Mari; Djamali, Arjang; Kaufman, Dixon B; Astor, Brad C

2016-07-01

Renin-angiotensin system (RAS) blockade reduces mortality in the general population and among non-dialysis-dependent patients with chronic kidney disease. The RAS blockade also decreases proteinuria and protects renal function in non-transplant patients with chronic kidney disease. It remains controversial, however, whether this translates to improved patient or graft survival among transplant recipients. We analyzed 2684 primary kidney transplant recipients at the University of Wisconsin in 1994 to 2010 who had a functioning graft at 6 months after transplantation. We assessed the association of RAS blockade with patient and graft survival using time-dependent Cox and marginal structural models. Three hundred seventy-seven deaths and 329 graft failures before death (638 total graft losses) occurred during a median of 5.4 years of follow-up. The RAS blockade was associated with an adjusted-hazard ratio of 0.63 (95% confidence interval, 0.53-0.75) for total graft loss, 0.69 (0.55-0.86) for death, and 0.62 (0.49-0.78) for death-censored graft failure. The associations of RAS blockade with a lower risk of total graft loss and mortality were stronger with more severe proteinuria. The RAS blockade was associated with a 2-fold higher risk of hyperkalemia. Our findings suggest RAS blockade is associated with better patient and graft survival in renal transplant recipients.

Fillet quality and processing attributes of postsmolt Atlantic salmon, Salmo salar, fed a fishmeal-free diet and a fishmeal-based diet in recirculation aquaculture systems

USDA-ARS?s Scientific Manuscript database

Many studies have evaluated the adequacy of alternate ingredient diets for Atlantic salmon, Salmo salar, mainly with focus on fish performance and health; however, comprehensive analysis of fillet quality is lacking, particularly for salmon fed these diets in recirculation aquaculture systems (RAS)....

Novel Cardiac Intracrine Mechanisms Based on Ang-(1-12)/Chymase Axis Require a Revision of Therapeutic Approaches in Human Heart Disease.

PubMed

Reyes, Santiago; Varagic, Jasmina; Ahmad, Sarfaraz; VonCannon, Jessica; Kon, Neal D; Wang, Hao; Groban, Leanne; Cheng, Che Ping; Dell'Italia, Louis J; Ferrario, Carlos M

2017-02-01

Drugs targeting the renin-angiotensin system (RAS), namely angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers, are the most commonly prescribed drugs for patients with or at risk for cardiovascular events. However, new treatment strategies aimed at mitigating the rise of the heart failure pandemic are warranted because clinical trials show that RAS blockers have limited benefits in halting disease progression. The main goal of this review is to put forward the concept of an intracrine RAS signaling through the novel angiotensin-(1-12)/chymase axis as the main source of deleterious angiotensin II (Ang II) in cardiac maladaptive remodeling leading to heart failure (HF). Expanding traditional knowledge, Ang II can be produced in tissues independently from the circulatory renin-angiotensin system. In the heart, angiotensin-(1-12) [Ang-(1-12)], a recently discovered derivative of angiotensinogen, is a precursor of Ang II, and chymase rather than ACE is the main enzyme contributing to the direct production of Ang II from Ang-(1-12). The Ang-(1-12)/chymase axis is an independent intracrine pathway accounting for the trophic, contractile, and pro-arrhythmic Ang II actions in the human heart. Ang-(1-12) expression and chymase activity have been found elevated in the left atrial appendage of heart disease subjects, suggesting a pivotal role of this axis in the progression of HF. Recent meta-analysis of large clinical trials on the use of ACE inhibitors and angiotensin receptor blockers in cardiovascular disease has demonstrated an imbalance between patients that significantly benefit from these therapeutic agents and those that remain at risk for heart disease progression. Looking to find an explanation, detailed investigation on the RAS has unveiled a previously unrecognized complexity of substrates and enzymes in tissues ultimately associated with the production of Ang II that may explain the shortcomings of ACE inhibition and angiotensin receptor blockade. Discovery of the Ang-(1-12)/chymase axis in human hearts, capable of producing Ang II independently from the circulatory RAS, has led to the notion that a tissue-delimited RAS signaling in an intracrine fashion may account for the deleterious effects of Ang II in the heart, contributing to the transition from maladaptive cardiac remodeling to heart failure. Targeting intracellular RAS signaling may improve current therapies aimed at reducing the burden of heart failure.

Trabecular meshwork ECM remodeling in glaucoma: could RAS be a target?

PubMed

Agarwal, Puneet; Agarwal, Renu

2018-06-14

Disturbances of extracellular matrix (ECM) homeostasis in trabecular meshwork (TM) cause increased aqueous outflow resistance leading to elevated intraocular pressure (IOP) in glaucomatous eyes. Therefore, restoration of ECM homeostasis is a rational approach to prevent disease progression. Since renin-angiotensin system (RAS) inhibition positively alters ECM homeostasis in cardiovascular pathologies involving pressure and volume overload, it is likely that RAS inhibitors reduce IOP primarily by restoring ECM homeostasis. Areas covered: Current evidence showing the presence of RAS components in ocular tissue and its role in regulating aqueous humor dynamics is briefly summarized. The role of RAS in ECM remodeling is discussed both in terms of its effects on ECM synthesis and its breakdown. The mechanisms of ECM remodeling involving interactions of RAS with transforming growth factor-β, Wnt/β-catenin signaling, bone morphogenic proteins, connective tissue growth factor, and matrix metalloproteinases in ocular tissue are discussed. Expert opinion: Current literature strongly indicates a significant role of RAS in ECM remodeling in TM of hypertensive eyes. Hence, IOP-lowering effect of RAS inhibitors may primarily be attributed to restoration of ECM homeostasis in aqueous outflow pathways rather than its vascular effects. However, the mechanistic targets for RAS inhibitors have much wider distribution and consequences, which remain relatively unexplored in TM.

Circadian rhythm of blood pressure and the renin-angiotensin system in the kidney.

PubMed

Ohashi, Naro; Isobe, Shinsuke; Ishigaki, Sayaka; Yasuda, Hideo

2017-05-01

Activation of the intrarenal renin-angiotensin system (RAS) has a critical role in the pathophysiology of the circadian rhythm of blood pressure (BP) and renal injury, independent of circulating RAS. Although it is clear that the circulating RAS has a circadian rhythm, reports of a circadian rhythm in tissue-specific RAS are limited. Clinical studies evaluating intrarenal RAS activity by urinary angiotensinogen (AGT) levels have indicated that urinary AGT levels were equally low during both the daytime and nighttime in individuals without chronic kidney disease (CKD) and that urinary AGT levels were higher during the daytime than at nighttime in patients with CKD. Moreover, urinary AGT levels of the night-to-day (N/D) ratio of urinary AGT were positively correlated with the levels of N/D of urinary protein, albumin excretion and BP. In addition, animal studies have demonstrated that the expression of intrarenal RAS components, such as AGT, angiotensin II (AngII) and AngII type 1 receptor proteins, increased and peaked at the same time as BP and urinary protein excretion during the resting phase, and the amplitude of the oscillations of these proteins was augmented in a chronic progressive nephritis animal compared with a control. Thus, the circadian rhythm of intrarenal RAS activation may lead to renal damage and hypertension, which both are associated with diurnal variations in BP. It is possible that augmented glomerular permeability increases AGT excretion levels into the tubular lumen and that circadian fluctuation of glomerular permeability influences the circadian rhythm of the intrarenal RAS.

A Corpus-Based Lexical Study on Frequency and Distribution of Coxhead's Awl Word Families in Medical Research Articles (RAs)

ERIC Educational Resources Information Center

Chen, Qi; Guang-Chun, Ge

2007-01-01

We conducted a lexical study on the word frequency and the text coverage of the 570 word families from Coxhead's Academic Word List (AWL) in medical research articles (RAs) based on a corpus of 50 medical RAs written in English with 190425 running words. By computer analysis, we found that the text coverage of the AWL words accounted for around…

Immunohistochemical evalulation of activated Ras and Rac1 as potential downstream effectors of aquaporin-5 in breast cancer in vivo.

PubMed

Jensen, Helene H; Login, Frédéric H; Park, Ji-Young; Kwon, Tae-Hwan; Nejsum, Lene N

2017-11-25

Aberrant levels of aquaporin-5 (AQP5) expression have been observed in several types of cancer, including breast cancer, where AQP5 overexpression is associated with metastasis and poor prognosis. In cultured cancer cells, AQP5 facilitates cell migration and activates Ras signaling. Both increased cell migration and Ras activation are associated with cancer metastasis, but so far it is unknown if AQP5 also affects these processes in vivo. Therefore, we investigated if high AQP5 expression in breast cancer tissue correlated with increased activation of Ras and of Rac1, which is a GTPase also involved in cell migration. This was accomplished by immunohistochemical analysis of invasive ductal carcinoma of breast tissue sections from human patients, followed by qualitative and quantitative correlation analysis between AQP5 and activated Ras and Rac1. Immunohistochemistry revealed that activation of Ras and Rac1 was positively correlated. There was, however, no correlation between high AQP5 expression and activation of Ras, whereas a nonsignificant, but positive, tendency between the levels of AQP5 and activated Rac1 levels was observed. In summary, this is the first report that correlates AQP5 expression levels to downstream signaling partners in breast cancer tissue sections. The results suggest Rac1 as a potential downstream signaling partner of AQP5 in vivo. Copyright © 2017 Elsevier Inc. All rights reserved.

Structural Patterns in Empirical Research Articles: A Cross-Disciplinary Study

ERIC Educational Resources Information Center

Lin, Ling; Evans, Stephen

2012-01-01

This paper presents an analysis of the major generic structures of empirical research articles (RAs), with a particular focus on disciplinary variation and the relationship between the adjacent sections in the introductory and concluding parts. The findings were derived from a close "manual" analysis of 433 recent empirical RAs from high-impact…

Deoxycholate-hydrogels: novel drug carrier systems for topical use.

PubMed

Valenta, C; Nowack, E; Bernkop-Schnürch, A

1999-08-05

Na-deoxycholate (Na-DOC) forms a viscous thixotropic gel when in contact with excess buffer systems. The resulting gels have been tested as novel drug carrier systems for topical use. The influence of differing amounts of mannitol, glycerol and xylitol on the viscous modulus (G"/Pa) was evaluated by oscillatory measurements. Na-DOC (0.5%) in phosphate buffered saline (PBS) with 5% mannitol was chosen as an optimised formulation, taking into account viscosity, distribution and appearance. The release rate of the model drug rutin through an artificial membrane was higher than those from hydroxyethylcellulose- (HEC) and sodium polyacrylate (NaC934)-gels; permeation through excised rat skin was also highest for the Na-DOC systems. The results indicate that Na-DOC significantly increases the membrane permeability. The microbial stability was in the same range as HEC- and NaC934-gels, making a preservation necessary. Na-DOC-gels are novel low molecular weight, multifunctional drug carriers, which also act as penetration enhancers. Their thixotropy is an additional advantage for better application to large skin areas, nasal, vaginal and buccal membranes. Therefore, Na-DOC-gels can be considered promising, alternative drug carrier systems for topical pharmaceutical as well as cosmetic use.

Experimental Investigation and Analysis of HEC-6 River Morphological Model

NASA Astrophysics Data System (ADS)

Tingsanchali, Tawatchai; Supharatid, Seree

1996-05-01

Only comparatively few experimental studies have been carried out to investigate the performance of the HEC-6 river morphological model. The model was developed by the Hydrologic Engineering Center of the US Army Corps of Engineers. In this study, experiments were carried out in a 20 m long concrete flume 0.6 m wide with varying rectangular cross-sections. The channel bed is paved with uniform sand of D50 = 0.9 mm and D90 = 1.2 mm within the test reach of 12 m. Two types of experiments were carried out with sediment transport, one under steady uniform flow and another under steady non-uniform flow conditions. Nine steady uniform flow experiments were carried out to compare the measured equilibrium relationship of flow and sediment transport rate with two bedload formulae, namely, Du Boys and Meyer-Peter and Muller, and with three total load formulae, namely, Toffaleti, Laursen and Yang. It was found that even though the sediment transport consists of a certain portion of bedload, the total load formulae give satisfactory results and better agreement than the two bedload formulae. Five steady non-uniform flow experiments were carried out under various conditions of varying bed profile and channel width and also with sediment addition and withdrawal. The measured transient water surface and bed profiles are compared with the computed results from the HEC-6 model. It was found that the Toffaleti and Yang total load formulae used in the HEC-6 model give the most satisfactory prediction of actual bed profiles under various conditions of non-uniform flow and sediment transport. The effects of Manning's n, variations of sediment inflow, various sediment transport formulae, sediment grain size and the model numerical parameters, i.e. distance interval x and numerical weighting factor, on the computed water surface and bed profiles were determined. It was found that the selection of the sediment transport formulae has the most significant effect on the computed results. It can be concluded that the HEC-6 model can predict satisfactorily a long-term average pattern of local scour and deposition along a channel with either a small abrupt change in geometry or gradually varying cross-sections. However, the accuracy of the model prediction is reduced in the regions where highly non-uniform flow occurs.

Cetuximab in treatment of metastatic colorectal cancer: final survival analyses and extended RAS data from the NORDIC-VII study.

PubMed

Guren, Tormod Kyrre; Thomsen, Maria; Kure, Elin H; Sorbye, Halfdan; Glimelius, Bengt; Pfeiffer, Per; Österlund, Pia; Sigurdsson, Fridbjörn; Lothe, Inger Marie Bowitz; Dalsgaard, Astrid Marie; Skovlund, Eva; Christoffersen, Thoralf; Tveit, Kjell Magne

2017-05-09

The NORDIC-VII study is a randomised phase III trial of cetuximab plus continuous or intermittent fluorouracil, folinic acid, and oxaliplatin (Nordic FLOX) vs FLOX alone in first-line treatment of metastatic colorectal cancer. The present report presents an updated and final survival analysis with BRAF and extended RAS mutational status, 5 years after the primary analysis. A total of 566 patients were included in the intention-to-treat (ITT) population of the NORDIC-VII study. Updated survival status was obtained from 176 patients who were alive in the primary survival analyses. Samples from 223 tumours previously found to be KRAS (exon 2) and BRAF (V600E) wild-type, were re-analysed for KRAS (exons 3 and 4) and NRAS (exons 2-4) mutations. Including the extended RAS analyses, RAS and BRAF mutational status was available from 457 patients (81% of the ITT population). RAS was mutated in 46% and BRAF in 12% of the tumours. RAS and BRAF, if mutated, were negative prognostic factors. The updated analyses confirmed the finding of the primary report that cetuximab did not provide any additional benefit when added to FLOX in patients with RAS/BRAF wild-type tumours, neither on progression-free nor overall survival. However, the outcomes in a subset of patients, which, after the first eight treatment cycles, received cetuximab alone, suggested a beneficial effect of cetuximab monotherapy. Adding cetuximab to Nordic FLOX did not provide any clinical benefit, but the data suggested an effect of cetuximab monotherapy in patients with RAS/BRAF wild-type tumours in the NORDIC-VII cohort. The data were compatible with a negative interaction between cetuximab and the Nordic FLOX chemotherapy backbone.

Exploring the Factor Structure of a Recovery Assessment Measure among Substance-Abusing Youth.

PubMed

Gonzales, Rachel; Hernandez, Mayra; Douglas, Samantha B; Yu, Chong Ho

2015-01-01

To date, the measurement of recovery in the field of substance abuse is limited. Youth recovery from substance abuse is an important area to consider, given the complexities of such issues. The Recovery Assessment Scale (RAS) has been validated with mental health patient populations; however, its measurement characteristics have not been examined for individuals in substance abuse treatment. The current study explored the factor structure of the RAS with a sample of 80 substance-abusing youth who participated in a pilot aftercare study (Mage 20.5, SD=3.5; 71.3% male). Reliability analysis showed an internal consistency of α=.90 for the entire RAS measure among the youth sample. Results of exploratory factor analysis identified the following four factors: personal determination, skills for recovery, self-control in recovery, and social support/moving beyond recovery among the substance-abusing youth sample. The RAS also demonstrated sound convergent and divergent validity in comparison to other validated measures of functioning, sobriety, and well-being. Collectively, results support that the RAS has adequate psychometric properties for measuring recovery among substance-abusing youth.

HPMC supplementation reduces abdominal fat content, intestinal permeability, inflammation, and insulin resistance in diet-induced obese mice

USDA-ARS?s Scientific Manuscript database

Cationic hydroxyethyl cellulose (cHEC) , was fed to hamsters to determine if this new soluble fiber had an effect on hypercholesterolemia and dyslipidemia associated with cardiovascular disease. In this study, Golden Syrian hamsters were supplemented with 3-8% cHEC or microcrystalline cellulose (MC...

Does Homeownership Counseling Affect the Prepayment and Default Behavior of Affordable Mortgage Borrowers?

ERIC Educational Resources Information Center

Quercia, Roberto; Spader, Jonathan

2008-01-01

The lack of industry wide data on homeownership education and counseling (HEC) programs has severely limited evaluation. In particular, very little evidence exists on the relationship between HEC completion and loan prepayment, an outcome of interest to both mortgage lenders and consumer advocates. Where mortgage prepayment directly influences the…

Simulation of Sediment Transport Caused by Landslide at Nanhua Reservoir Watershed in Southern Taiwan

NASA Astrophysics Data System (ADS)

Lee, Ming-Hsi; Huang, Cong-Gi; Lin, Huan-Hsuan

2016-04-01

As a result of heavy rainfall, steep topography, young and weak geological formations, earthquakes, loose soils, slope land cultivation and other human disturbance, much area in Taiwan are prone to the occurrence of disastrous mass movements such as landslides and sediment disasters. During recent years, the extreme rainfall events brought huge amounts of rainfall and triggered severe changes in watershed environments. Typhoon Morakot in August 2009 caused severe landslides, debris flow, flooding and sediment disasters induced by record-break rainfall. The maximum rainfall of mountain area in Chiayi, Tainan, Kaohsiung and Pingtung County were over 2,900 mm. The study area is located at Nanhua reservoir watershed in southern Taiwan. The numerical model (HEC-RAS 4.1 and FLO-2D) will be used to simulate the sediment transport caused by landslide and the study will find out the separating location of erosion and deposition in the river, the danger area of riverbank, and the safety of the river terrace village under the return period of 50-year, 100-year and 200-year (such as Typhoon Morakot). The results of this study can provide for the disaster risk management of administrative decisions to lessen the impacts of natural hazards and may also be useful for time-space variation of sediment disasters caused by Climate Change.

Flood hazard mapping of Palembang City by using 2D model

NASA Astrophysics Data System (ADS)

Farid, Mohammad; Marlina, Ayu; Kusuma, Muhammad Syahril Badri

2017-11-01

Palembang as the capital city of South Sumatera Province is one of the metropolitan cities in Indonesia that flooded almost every year. Flood in the city is highly related to Musi River Basin. Based on Indonesia National Agency of Disaster Management (BNPB), the level of flood hazard is high. Many natural factors caused flood in the city such as high intensity of rainfall, inadequate drainage capacity, and also backwater flow due to spring tide. Furthermore, anthropogenic factors such as population increase, land cover/use change, and garbage problem make flood problem become worse. The objective of this study is to develop flood hazard map of Palembang City by using two dimensional model. HEC-RAS 5.0 is used as modelling tool which is verified with field observation data. There are 21 sub catchments of Musi River Basin in the flood simulation. The level of flood hazard refers to Head Regulation of BNPB number 2 in 2012 regarding general guideline of disaster risk assessment. The result for 25 year return per iod of flood shows that with 112.47 km2 area of inundation, 14 sub catchments are categorized in high hazard level. It is expected that the hazard map can be used for risk assessment.

Hydraulic modeling of flow impact on bridge structures: a case study on Citarum bridge

NASA Astrophysics Data System (ADS)

Siregar, R. I.

2018-02-01

Flood waves because of the rapid catchment response to high intense rainfall, breaches of flood defenses may induce huge impact forces on structures, causing structural damage or even failures. Overflowing stream that passes over the bridge, it means to discharge flood water level is smaller than the capacity of the river flow. In this study, the researches present the methodological approach of flood modeling on bridge structures. The amount of force that obtained because of the hydrostatic pressure received by the bridge at the time of the flood caused the bridge structure disrupted. This paper presents simulation of flow impact on bridge structures with some event flood conditions. Estimating the hydrostatic pressure developed new model components, to quantify the flow impact on structures. Flow parameters applied the model for analyzing, such as discharge, velocity, and water level or head that effect of bridge structures. The simulation will illustrate the capability of bridge structures with some event flood river and observe the behavior of the flow that occurred during the flood. Hydraulic flood modeling use HEC-RAS for simulation. This modeling will describe the impact on bridge structures. Based on the above modelling resulted, in 2008 has flood effect more than other years on the Citarum Bridge, because its flow overflow on the bridge.

K-RasG12D–induced T-cell lymphoblastic lymphoma/leukemias harbor Notch1 mutations and are sensitive to γ-secretase inhibitors

PubMed Central

Cornejo, Melanie G.; Scholl, Claudia; Liu, Jianing; Leeman, Dena S.; Haydu, J. Erika; Fröhling, Stefan; Lee, Benjamin H.; Gilliland, D. Gary

2008-01-01

To study the impact of oncogenic K-Ras on T-cell leukemia/lymphoma development and progression, we made use of a conditional K-RasG12D murine knockin model, in which oncogenic K-Ras is expressed from its endogenous promoter. Transplantation of whole bone marrow cells that express oncogenic K-Ras into wild-type recipient mice resulted in a highly penetrant, aggressive T-cell leukemia/lymphoma. The lymphoblasts were composed of a CD4/CD8 double-positive population that aberrantly expressed CD44. Thymi of primary donor mice showed reduced cellularity, and immunophenotypic analysis demonstrated a block in differentiation at the double-negative 1 stage. With progression of disease, approximately 50% of mice acquired Notch1 mutations within the PEST domain. Of note, primary lymphoblasts were hypersensitive to γ-secretase inhibitor treatment, which is known to impair Notch signaling. This inhibition was Notch-specific as assessed by down-regulation of Notch1 target genes and intracellular cleaved Notch. We also observed that the oncogenic K-Ras-induced T-cell disease was responsive to rapamycin and inhibitors of the RAS/MAPK pathway. These data indicate that patients with T-cell leukemia with K-Ras mutations may benefit from therapies that target the NOTCH pathway alone or in combination with inhibition of the PI3K/AKT/MTOR and RAS/MAPK pathways. PMID:18663146

Vascular endothelial growth factor during hypoglycemia in patients with type 1 diabetes mellitus: relation to cognitive function and renin-angiotensin system activity.

PubMed

Kristensen, Peter Lommer; Høi-Hansen, Thomas; Boomsma, Frans; Pedersen-Bjergaard, Ulrik; Thorsteinsson, Birger

2009-10-01

In healthy adults, levels of vascular endothelial growth factor (VEGF) increase in response to mild hypoglycemia. VEGF is implicated in glucose transport over the blood-brain barrier, and the increase during hypoglycemia has been positively correlated with preservation of cognitive function during hypoglycemia. High activity in the renin-angiotensin system (RAS) is associated with an increased risk of severe hypoglycemia in patients with type 1 diabetes mellitus. Renin-angiotensin system possibly exerts its mechanism in hypoglycemia via VEGF. We studied the impact of mild hypoglycemia on plasma VEGF in patients with type 1 diabetes mellitus and high or low RAS activity and analyzed associations between VEGF levels and cognitive function during hypoglycemia. Eighteen patients with type 1 diabetes mellitus-9 with high and 9 with low RAS activity-underwent a single-blinded, placebo-controlled, crossover study with either mild hypoglycemia or stable glycemia. Cognitive function was assessed by the California Cognitive Assessment Package and the Alzheimer Quick Test. Nadir plasma glucose was 2.2 (0.3) mmol/L. During the control study, plasma VEGF did not change. During hypoglycemia, plasma VEGF increased from 39 to 58 pg/L in the high-RAS group (P = .004) and from 76 to 109 pg/L in the low-RAS group (P = .01), with no difference between RAS groups (P = .9). A weak association between reduced preservation of cognitive function during hypoglycemia and low VEGF response was observed. Plasma VEGF levels increase during mild, short-term hypoglycemia in patients with type 1 diabetes mellitus. The VEGF response is not dependent on RAS activity and only weakly associated with preservation of cognitive function during hypoglycemia. Thus, the previously described association between low RAS activity and better cognitive performance during hypoglycemia does not seem to be mediated by VEGF.

Activation of K-ras by codon 13 mutations in C57BL/6 X C3H F1 mouse tumors induced by exposure to 1,3-butadiene.

PubMed

Goodrow, T; Reynolds, S; Maronpot, R; Anderson, M

1990-08-01

1,3-Butadiene has been detected in urban air, gasoline vapors, and cigarette smoke. It has been estimated that 65,000 workers are exposed to this chemical in occupational settings in the United States. Lymphomas, lung, and liver tumors were induced in female and male C57BL/6 X C3H F1 (hereafter called B6C3F1) mice by inhalation of 6.25 to 625 ppm 1,3-butadiene for 1 to 2 years. The objective of this study was to examine these tumors for the presence of activated protooncogenes by the NIH 3T3 transfection and nude mouse tumorigenicity assays. Transfection of DNA isolated from 7 of 9 lung tumors and 7 of 12 liver tumors induced morphological transformation of NIH 3T3 cells. Southern blot analysis indicated that the transformation induced by 6 lung and 3 liver tumor DNA samples was due to transfer of a K-ras oncogene. Four of the 7 liver tumors that were positive upon transfection contained an activated H-ras gene. The identity of the transforming gene in one of the lung tumors has not been determined but was not a member of the ras family or a met or raf gene. Eleven 1,3-butadiene-induced lymphomas were examined for transforming genes using the nude mouse tumorigenicity assay. Activated K-ras genes were detected in 2 of the 11 lymphomas assayed. DNA sequencing of polymerase chain reaction-amplified ras gene exons revealed that 9 of 11 of the activating K-ras mutations were G to C transversions in codon 13. One liver tumor contained an activated K-ras gene with mutations in both codons 60 and 61. The activating mutation in one of the K-ras genes from a lymphoma was not identified but DNA sequence analysis of amplified regions in proximity to codons 12, 13, and 61 demonstrated that the mutation was not located in or near these codons. Activation of K-ras genes by codon 13 mutations has not been found in any lung or liver tumors or lymphomas from untreated B6C3F1 mice. Thus, the K-ras activation found in 1,3-butadiene-induced B6C3F1 mouse tumors probably occurred as a result of genotoxic effects of this chemical. The oncogenes most frequently detected in human pulmonary adenocarcinomas are K-ras genes. Activated K-ras genes have also been found in some human lymphomas. This suggest that activation of K-ras may be important in the induction of human pulmonary adenocarcinomas and lymphomas.(ABSTRACT TRUNCATED AT 400 WORDS)

Retrospective study of RAS/PIK3CA/BRAF tumor mutations as predictors of response to first-line chemotherapy with bevacizumab in metastatic colorectal cancer patients.

PubMed

Nakayama, Izuma; Shinozaki, Eiji; Matsushima, Tomohiro; Wakatsuki, Takeru; Ogura, Mariko; Ichimura, Takashi; Ozaka, Masato; Takahari, Daisuke; Suenaga, Mitsukuni; Chin, Keisho; Mizunuma, Nobuyuki; Yamaguchi, Kensei

2017-01-09

After analysis of minor RAS mutations (KRAS exon 3, 4/NRAS) in the FIRE-3 and PRIME studies, an expanded range of RAS mutations were established as a negative predictive marker for the efficacy of anti-EGFR antibody treatment. BRAF and PIK3CA mutations may be candidate biomarkers for anti-EGFR targeted therapies. However, it remains unknown whether RAS/PIK3CA/BRAF tumor mutations can predict the efficacy of bevacizumab in metastatic colorectal cancer. We assessed whether selection according to RAS/PIK3CA/BRAF mutational status could be beneficial for patients treated with bevacizumab as first-line treatment for metastatic colorectal cancer. Of the 1001 consecutive colorectal cancer patients examined for RAS, PIK3CA, and BRAF tumor mutations using a multiplex kit (Luminex®), we studied 90 patients who received combination chemotherapy with bevacizumab as first-line treatment for metastatic colorectal cancer. The objective response rate (ORR) and progression-free survival (PFS) were evaluated according to mutational status. The ORR was higher among patients with wild-type tumors (64.3%) compared to those with tumors that were only wild type with respect to KRAS exon 2 (54.8%), and the differences in ORR between patients with wild-type and mutant-type tumors were greater when considering only KRAS exon 2 mutations (6.8%) rather than RAS/PIK3CA/BRAF mutations (18.4%). There were no statistically significant differences in ORR or PFS between all wild-type tumors and tumors carrying any of the mutations. Multivariate analysis revealed that liver metastasis and RAS and BRAF mutations were independent negative factors for disease progression after first-line treatment with bevacizumab. Patient selection according to RAS/PIK3CA/BRAF mutations could help select patients who will achieve a better response to bevacizumab treatment. We found no clinical benefit of restricting combination therapy with bevacizumab for metastatic colorectal cancer patients with EGFR-wild type tumors.

Associations of Proton-Pump Inhibitors and H2 Receptor Antagonists with Chronic Kidney Disease: A Meta-Analysis.

PubMed

Wijarnpreecha, Karn; Thongprayoon, Charat; Chesdachai, Supavit; Panjawatanana, Panadeekarn; Ungprasert, Patompong; Cheungpasitporn, Wisit

2017-10-01

The aim of this meta-analysis was to assess the risks of chronic kidney disease (CKD) and/or end-stage kidney disease (ESRD) in patients who are taking proton-pump inhibitors (PPIs) and/or H2 receptor antagonists (H2RAs). Comprehensive literature review was conducted utilizing MEDLINE and EMBASE databases through April 2017 to identify all studies that investigated the risks of CKD or ESRD in patients taking PPIs/H2RAs versus those without PPIs/H2RAs. Pooled risk ratios (RR) and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method of DerSimonian and Laird. The protocol for this study is registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42017067252). Five studies with 536,902 participants were patients were identified and included in the data analysis. When compared with non-PPIs users, the pooled risk ratio (RR) of CKD or ESRD in patients with PPI use was 1.33 (95% CI 1.18-1.51). Pre-specified subgroup analysis (stratified by CKD or ESRD status) demonstrated pooled RRs of 1.22 (95% CI 1.14-1.30) for association between PPI use and CKD and 1.88 (95% CI 1.71-2.06) for association between PPI use and ESRD, respectively. However, there was no association between the use of H2RAs and CKD with a pooled RR of 1.02 (95% CI 0.83-1.25). When compared with the use of H2RAs, the pooled RR of CKD in patients with PPI use was 1.29 (95% CI 1.22-1.36). Our study demonstrates statistically significant 1.3-fold increased risks of CKD and ESRD in patients using PPIs, but not in patients using H2RAs.

Nanofluidic Digital PCR and Extended Genotyping of RAS and BRAF for Improved Selection of Metastatic Colorectal Cancer Patients for Anti-EGFR Therapies.

PubMed

Azuara, Daniel; Santos, Cristina; Lopez-Doriga, Adriana; Grasselli, Julieta; Nadal, Marga; Sanjuan, Xavier; Marin, Fátima; Vidal, Joana; Montal, Robert; Moreno, Victor; Bellosillo, Beatriz; Argiles, Guillem; Elez, Elena; Dienstmann, Rodrigo; Montagut, Clara; Tabernero, Josep; Capellá, Gabriel; Salazar, Ramon

2016-05-01

The clinical significance of low-frequent RAS pathway-mutated alleles and the optimal sensitivity cutoff value in the prediction of response to anti-EGFR therapy in metastatic colorectal cancer (mCRC) patients remains controversial. We aimed to evaluate the added value of genotyping an extended RAS panel using a robust nanofluidic digital PCR (dPCR) approach. A panel of 34 hotspots, including RAS (KRAS and NRAS exons 2/3/4) and BRAF (V600E), was analyzed in tumor FFPE samples from 102 mCRC patients treated with anti-EGFR therapy. dPCR was compared with conventional quantitative PCR (qPCR). Response rates, progression-free survival (PFS), and overall survival (OS) were correlated to the mutational status and the mutated allele fraction. Tumor response evaluations were not available in 9 patients and were excluded for response rate analysis. Twenty-two percent of patients were positive for one mutation with qPCR (mutated alleles ranged from 2.1% to 66.6%). Analysis by dPCR increased the number of positive patients to 47%. Mutated alleles for patients only detected by dPCR ranged from 0.04% to 10.8%. An inverse correlation between the fraction of mutated alleles and radiologic response was observed. ROC analysis showed that a fraction of 1% or higher of any mutated alleles offered the best predictive value for all combinations of RAS and BRAF analysis. In addition, this threshold also optimized prediction both PFS and OS. We conclude that mutation testing using an extended gene panel, including RAS and BRAF with a threshold of 1% improved prediction of response to anti-EGFR therapy. Mol Cancer Ther; 15(5); 1106-12. ©2016 AACR. ©2016 American Association for Cancer Research.

An Investigation of Generic Structures of Pakistani Doctoral Thesis Acknowledgements

ERIC Educational Resources Information Center

Rofess, Sakander; Mahmood, Muhammad Asim

2015-01-01

This paper investigates Pakistani doctoral thesis acknowledgements from genre analysis perspective. A corpus of 235 PhD thesis acknowledgements written in English was taken from Pakistani doctoral theses collected from eight different disciplines. HEC Research Repository of Pakistan was used as a data sources. The theses written by Pakistani…

Development of curcumin-loaded poly(hydroxybutyrate- co-hydroxyvalerate) nanoparticles as anti-inflammatory carriers to human-activated endothelial cells

NASA Astrophysics Data System (ADS)

Simion, Viorel; Stan, Daniela; Gan, Ana-Maria; Pirvulescu, Monica Madalina; Butoi, Elena; Manduteanu, Ileana; Deleanu, Mariana; Andrei, Eugen; Durdureanu-Angheluta, Anamaria; Bota, Marian; Enachescu, Marius; Calin, Manuela; Simionescu, Maya

2013-12-01

Curcumin (Cm)-loaded poly(hydroxybutyrate- co-hydroxyvalerate) (PHBV) nanoparticles (CmPN) were obtained and characterized and their effect on human endothelial cells (HEC) was assessed. Different CmPN formulations have been prepared using the emulsion solvent evaporation technique, and characterized for size, structure, Zeta potential, Cm entrapment efficiency, and in vitro Cm release. CmPN cytotoxicity and cellular uptake have been followed using HEC. Also, the effect of CmPN treatment on the p38MAPK signaling pathway in endothelial cells was investigated. The results obtained by electron and atomic force microscopy revealed the spherical shape of the CmPN formulation. Based on size and encapsulation efficiency, the CmPN formulation with the average diameter of 186 nm and with the highest encapsulation efficiency (83 %) has been used in the further studies. The release of Cm from CmPN was 18 % after 8 h of incubation at 37 °C, followed by a slow release until 144 h, when it reached 44 %, indicating a controlled release. CmPN are taken up by HEC and exhibited low cytotoxicity at concentrations up to 10 μM. The pre-treatment of HEC with CmPN before exposure to tumor necrosis factor-alpha (TNF-α) determined a decrease of p38MAPK phosphorylation. In conclusion, Cm encapsulated into PHBV nanoparticles, at concentration up to 10 μM, has low cytotoxicity and display anti-inflammatory activity on TNF-α-activated HEC by suppressing the phosphorylation of p38MAPK.

RAS in the central nervous system: Potential role in neuropsychiatric disorders.

PubMed

Rocha, Natalia Pessoa; Simões e Silva, Ana Cristina; Prestes, Thiago Ruiz Rodrigues; Feracin, Victor; Machado, Caroline Amaral; Ferreira, Rodrigo Novaes; Teixeira, Antonio Lucio; de Miranda, Aline Silva

2018-02-25

The Renin-Angiotensin System (RAS) is a key regulator of cardiovascular and renal homeostasis, but also plays important roles in mediating physiological functions in the central nervous system (CNS). The effects of the RAS were classically described as mediated by angiotensin (Ang) II via angiotensin type 1 (AT1) receptors. However, another arm of the RAS formed by the angiotensin converting enzyme 2 (ACE2), Ang-(1-7) and the Mas receptor has been a matter of investigation due to its important physiological roles, usually counterbalancing the classical effects exerted by Ang II. We aim to provide an overview of effects elicited by the RAS, especially Ang-(1-7), in the brain. We also aim to discuss the therapeutic potential for neuropsychiatric disorders of the modulation of RAS. We carried out an extensive literature search in PubMed central. Within the brain, Ang-(1-7) contributes to the regulation of blood pressure by acting at regions that control cardiovascular functions. In contrast with Ang II, Ang-(1-7) improves baroreflex sensitivity and plays an inhibitory role in hypothalamic noradrenergic neurotransmission. Ang-(1-7) not only exerts effects related to blood pressure regulation, but also acts as a neuroprotective component of the RAS, for instance, by reducing cerebral infarct size, inflammation, oxidative stress and neuronal apoptosis. Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and haemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

Sleep Disruption is Associated with Increased Ventricular Ectopy and Cardiac Arrest in Hospitalized Adults

PubMed Central

Miner, Steven Edward Stuart; Pahal, Dev; Nichols, Laurel; Darwood, Amanda; Nield, Lynne Elizabeth; Wulffhart, Zaev

2016-01-01

Study Objectives: To determine whether sleep disruption increases ventricular ectopy and the risk of cardiac arrest in hospitalized patients. Methods: Hospital emergency codes (HEC) trigger multiple hospital-wide overhead announcements. In 2014 an electronic “code white” program was instituted to protect staff from violent patients. This resulted in an increase in nocturnal HEC. Telemetry data was examined between September 14 and October 2, 2014. The frequency of nocturnal announcements was correlated with changes in frequency of premature ventricular complexes per hour (PVC/h). Cardiac arrest data were examined over a 3-y period. All HEC were assumed to have triggered announcements. The relationship between nocturnal HEC and the incidence of subsequent cardiac arrest was examined. Results: 2,603 hours of telemetry were analyzed in 87 patients. During nights with two or fewer announcements, PVC/h decreased 33% and remained 30% lower the next day. On nights with four or more announcements, PVC/h increased 23% (P < 0.001) and further increased 85% the next day (P = 0.001). In 2014, following the introduction of the code white program, the frequency of all HEC increased from 1.1/day to 6.2/day (P < 0.05). The frequency of cardiac arrest/24 h rose from 0.46/day in 2012–2013 to 0.62/day in 2014 (P = 0.001). During daytime hours (06:00–22:00), from 2012 through 2014, the frequency of cardiac arrest following zero, one or at least two nocturnal HEC were 0.331 ± 0.03, 0.396 ± 0.04 and 0.471 ± 0.09 respectively (R2 = 0.99, P = 0.03). Conclusions: Sleep disruption is associated with increased ventricular ectopy and increased frequency of cardiac arrest. Citation: Miner SE, Pahal D, Nichols L, Darwood A, Nield LE, Wulffart Z. Sleep disruption is associated with increased ventricular ectopy and cardiac arrest in hospitalized adults. SLEEP 2016;39(4):927–935. PMID:26715226

Development of swelling/floating gastroretentive drug delivery system based on a combination of hydroxyethyl cellulose and sodium carboxymethyl cellulose for Losartan and its clinical relevance in healthy volunteers with CYP2C9 polymorphism.

PubMed

Chen, Ray-Neng; Ho, Hsiu-O; Yu, Chiao-Ya; Sheu, Ming-Thau

2010-01-31

The aim of this study was to develop an optimal gastroretentive drug delivery system (GRDDS) for administering Losartan. Additionally, the influence of optimized GRDDS on the bioavailability of Losartan and the formation extent of active metabolite E3174 by CYP2C9 polymorphism was investigated. Swellable and floatable GRDDS tablets combining hydroxyethyl cellulose (HEC), sodium carboxymethyl cellulose (NaCMC), and sodium bicarbonate were prepared at various compression pressures for evaluating swelling characteristics and floating capacity. Then Losartan was incorporated into optimized formulations for in vitro and in vivo characterizations. An appropriate ratio of HEC to NaCMC, addition of sodium bicarbonate, and compression at lower pressures resulted in the tablets floating over SGF for more than 16 h and swelling to 2 cm in diameter within 3h. The release patterns of Losartan from these tablets were pH-dependent. Results of the clinical trials showed that the mean bioavailability from GRD-A (HEC 91.67%, sodium bicarbonate 3.33% and Losartan 8.33%) was approximately 164%, relative to the immediate-release product (Cozaar). MRT and t(max) values were greater and C(max) values were lower for the GRDDS tablets compared with Cozaa. The lower bioavailability of Losartan in the CYP2C9*1/*1 subjects than CYP2C9*1/*3 subjects was found and could be due to the variety of enzymatic activity. Copyright 2009 Elsevier B.V. All rights reserved.

Cooperative transforming activities of ras, myc, and src viral oncogenes in nonestablished rat adrenocortical cells.

PubMed Central

MacAuley, A; Pawson, T

1988-01-01

Early-passage rat adrenocortical cells were infected with Kirsten murine sarcoma virus and MMCV mouse myc virus, two retroviruses carrying the v-Ki-ras and v-myc oncogenes, respectively. Efficient morphological transformation required coinfection with the two viruses, was dependent on the presence of high serum concentrations, and was not immediately accompanied by growth in soft agar. The doubly infected cells coordinately acquired the capacity for anchorage- and serum-independent growth during passage in culture. The appearance of such highly transformed cells was correlated with the emergence of a dominant clone, as suggested by an analysis of retrovirus integration sites. These results indicate that the concerted expression of v-Ki-ras and v-myc could induce rapid morphological transformation of nonestablished adrenocortical cells but that an additional genetic or epigenetic event was required to permit full transformation by these two oncogenes. In contrast, v-src, introduced by retrovirus infection in conjunction with v-myc, rapidly induced serum- and anchorage-independent growth. Therefore, the p60v-src protein-tyrosine kinase, unlike p21v-ras, is apparently not restricted in the induction of a highly transformed phenotype in adrenocortical cells. This system provides an in vitro model for the progressive transformation of epithelial cells by dominantly acting oncogenes. Images PMID:2846881

The muscular expression of RAS in patients with achalasia.

PubMed

Casselbrant, A; Kostic, S; Lönroth, H

2015-09-01

Angiotensin II (AngII) elicits smooth muscle contractions via activation of AngII type 1 receptor (AT1R) in the intestinal wall and in sphincter regions in several species. Achalasia is a rare swallowing disorder and is characterized by a loss of the wave-like contraction that forces food through the oesophagus and a failure of the lower oesophageal sphincter to relax during swallowing. The present study was undertaken to elucidate expression and distribution of a local renin-angiotensin system (RAS) in the muscular layer of distal normal human oesophagus as well as in patients with achalasia using western blot analysis, immunohistochemistry and polymerase chain reaction (PCR). AT1R, together with enzyme renin and cathepsin D expression were decreased in patients with achalasia. In contrast, the mast cells chymase, cathepsin G, neprilysin and the receptor for angiotensin 1-7 peptides, the MAS receptor, were increased in patients with achalasia. The results showed the existence of a local RAS in human oesophageal muscular layer. The enzymes responsible for AngII production are different and there has been a shift in receptor physiology from AT1R to MAS receptor in patients with achalasia. These changes in the RAS might play a significant role in the physiological motor control for patients with achalasia. © The Author(s) 2014.

Final Analysis of Outcomes and RAS/BRAF Status in a Randomized Phase 3 Study of Panitumumab and Best Supportive Care in Chemorefractory Wild Type KRAS Metastatic Colorectal Cancer.

PubMed

Kim, Tae Won; Elme, Anneli; Park, Joon Oh; Udrea, Anghel Adrian; Kim, Sun Young; Ahn, Joong Bae; Valencia, Ricardo Villalobos; Krishnan, Srinivasan; Manojlovic, Nebojsa; Guan, Xuesong; Lofton-Day, Catherine; Jung, A Scott; Vrdoljak, Eduard

2018-03-21

Tumor rat sarcoma gene (RAS) status is a negative predictive biomarker for anti-epidermal growth factor receptor (EGFR) therapy in metastatic colorectal cancer (mCRC). We analyzed outcomes according to RAS and v-Raf murine sarcoma viral oncogene homolog B (BRAF) mutational status, and evaluated early tumor shrinkage (ETS) and depth of response (DpR) for patients with wild type RAS. Patients with confirmed metastatic colon or rectum adenocarcinoma, wild type Kristen rat sarcoma gene tumor exon 2 status, clinical/radiologic disease progression or toxicity during irinotecan or oxaliplatin treatment, and no previous anti-EGFR therapy were randomized 1:1 to receive best supportive care (BSC) with or without panitumumab (6.0 mg/kg, intravenously, on day 1 of each 14-day cycle) in this open-label, multicenter, phase III study (20100007). RAS and BRAF mutation status were determined using Sanger sequencing. ETS was evaluated as maximum percentage change from baseline to week 8; DpR was calculated as the percentage change for tumor shrinkage at nadir versus baseline. Overall, 270 patients had RAS wild type mCRC (panitumumab with BSC, n = 142; BSC, n = 128). For patients with wild type RAS tumors, median overall survival (OS; hazard ratio [HR], 0.72; P = .015) and progression-free survival (PFS; HR, 0.45; P < .0001) were improved with panitumumab with BSC versus BSC. Similar improvements were seen for patients with wild type RAS, and wild type BRAF tumors (OS: HR, 0.75; P = .04; PFS: HR, 0.45; P < .0001). Median DpR was 16.9% for the evaluable panitumumab with BSC wild type RAS population. Overall, 69.5% experienced any type of tumor shrinkage at week 8; 38.2% experienced ≥ 20% shrinkage. Similar improvements in OS and PFS were seen with stratification according to ETS. This analysis showed that panitumumab improved outcomes in wild type RAS mCRC and indicated that ETS and DpR could be used as additional efficacy markers. Copyright © 2018 The Authors. Published by Elsevier Inc. All rights reserved.

[Robot-assisted surgery in the head and neck region].

PubMed

Hoffmann, T K; Friedrich, D T; Schuler, P J

2016-09-01

Robot-assisted surgery (RAS) in the head and neck region is believed to have a large potential for the improvement of patient care. Several systems with a master-slave setup are already in routine clinical use, particularly for oncologic surgery. Although specific patient groups may benefit from RAS, there is a lack of randomized clinical studies validating the advantages of these new technological systems in comparison to the existing standard procedures. On the other hand, RAS in the head and neck region is being constantly developed. Currently, the main limitations are the technical miniaturization of the tools and the loss of haptic feedback, as well as the high costs for acquisition and maintenance without financial reimbursement. In any case, the current generation of head and neck surgeons will face the technical, scientific, and ethical challenges of RAS.

[Angiotensin converting enzyme 2 and its emerging role in the regulation of the renin angiotensin system].

PubMed

Soler, María José; Lloveras, Josep; Batlle, Daniel

2008-07-12

The renin-angiotensin system (RAS) plays a key role in the regulation of cardiovascular and renal function. Thus, RAS blockade with an angiotensin-converting enzyme (ACE) and/or angiotensin receptor blocker decreases blood pressure, cardiovascular events, and delays the progression of kidney disease. The discovery of ACE2, a homologue of ACE, capable of degrading angiotensin II to angiotensin 1-7, may offer new insights into the RAS. In this review we discuss the possible protective role of ACE2 in different organs, namely heart, lungs and kidneys. The role of this enzyme is inferred from recent studies performed using genetically manipulated mice that lack the ACE2 gene and also mice treated with pharmacological ACE2 inhibitors. These results suggest that ACE2 might be a new therapeutic target within the RAS.

Comparison of real-world effectiveness between valsartan and non-RAS inhibitor monotherapy on the incidence of new diabetes in Chinese hypertensive patients: An electronic health recording system based study.

PubMed

Shen, Tian; Wang, Jiwei; Yu, Yingjun; Yu, Jinming

2018-05-21

This study aimed to compare the real-world effectiveness of valsartan and non renin-angiotensin system (non-RAS) agent monotherapy on the incidence of new on-set diabetes (NOD) in Chinese hypertensive patients. It was based on an electronic Health Recording System database from Minhang District of Shanghai. Hypertensive patients aged ≥18 years continuously taking either valsartan or non-RAS agent monotherapy for >12 months were included. Hazard ratios (HR) of NOD events were estimated using propensity score matching method and multivariate regression. Of 29295 patients, there were 2107 in valsartan group, 21397 in CCB group, 4094 in β-blockers group and 1697 in diuretics group. Two-year follow-up revealed NOD rates of 11.09 and 14.22 per 100 persons per year in valsartan and non-RAS inhibitor groups (HR = 0.77, 95% confidence interval 0.65-0.93, P = 0.006), respectively. Among non-RAS agents, CCB group had the highest incidence of NOD (21.72 per 100 persons per year). Comparisons between CCB sub-groups revealed the highest NOD incidence for nifedipine, followed by amlodipine and felodipine. NOD incidences in β-blockers and diuretics groups (11.70 and 10.50 per 100 persons per year, respectively) were not significantly different from valsartan group. Compared with non-RAS inhibitors, particularly CCBs, valsartan could significantly reduce the incidence of NOD.

Effects of reduced return activated sludge flows and volume on anaerobic zone performance for a septic wastewater biological phosphorus removal system.

PubMed

Magro, Daniel; Elias, Steven L; Randall, Andrew Amis

2005-01-01

Enhanced biological phosphorous removal (EBPR) performance was found to be adequate with reduced return-activated sludge (RAS) flows (50% of available RAS) to the anaerobic tank and smaller-than-typical anaerobic zone volume (1.08 hours hydraulic retention time [HRT]). Three identical parallel biological nutrient removal pilot plants were fed with strong, highly fermented (160 mg/L volatile fatty acids [VFAs]), domestic and industrial wastewater from a full-scale wastewater treatment facility. The pilot plants were operated at 100, 50, 40, and 25% RAS (percent of available RAS) flows to the anaerobic tank, with the remaining RAS to the anoxic tank. In addition, varying anaerobic HRT (1.08 and 1.5 hours) and increased hydraulic loading (35% increase) were examined. The study was divided into four phases, and the effect of these process variations on EBPR were studied by having one different variable between two identical systems. The most significant conclusion was that returning part of the RAS to the anaerobic zone did not decrease EBPR performance; instead, it changed the location of phosphorous release and uptake. Bringing less RAS to the anaerobic and more to the anoxic tank decreased anaerobic phosphorus release and increased anoxic phosphorus release (or decreased anoxic phosphorus uptake). Equally important is that, with VFA-rich influent wastewater, excessive anaerobic volume was shown to hurt overall phosphorus removal, even when it resulted in increased anaerobic phosphorus release.

Possible involvement of MSX-2 homeoprotein in v-ras-induced transformation.

PubMed

Takahashi, C; Akiyama, N; Kitayama, H; Takai, S; Noda, M

1997-04-01

A truncated MSX-2 homeoprotein was found to induce flat reversion when expressed in v-Ki-ras-transformed NIH3T3 cells. Although the expression of endogenous MSX-2 gene is low in most of the normal adult tissues examined, it is frequently activated in carcinoma-derived cell lines. Likewise, the gene is inactive in untransformed cells but is transcriptionally activated after transformation by v-Ki-ras oncogene, suggesting that the intact MSX-2 may play a positive, rather than suppressive, role in cell transformation. To test this possibility, we isolated a full-length human MSX-2 cDNA and tested its activities in two cell systems: fibroblast and myoblast. In NIH3T3 fibroblasts, although the gene by itself failed to confer a transformed phenotype, antisense MSX-2 cDNA as well as truncated MSX-2 cDNA interfered with the transforming activities of both v-Ki-ras and v-raf oncogene. In C2C12 myoblasts, MSX-2 was found to suppress MyoD gene expression, as do activated ras oncogenes, under certain culture conditions, and truncated MSX-2 cDNA was found to inhibit the activities of both MSX-2 and ras in this system as well. Our findings not only suggest that the truncated version MSX-2 may act as a dominant suppressor of intact MSX-2 but also raise the possibility that MSX-2 gene may be an important downstream target for the Ras signaling pathways.

Role of the intrarenal renin-angiotensin system in the progression of renal disease.

PubMed

Urushihara, Maki; Kagami, Shoji

2017-09-01

The intrarenal renin-angiotensin system (RAS) has many well-documented pathophysiologic functions in both blood pressure regulation and renal disease development. Angiotensin II (Ang II) is the major bioactive product of the RAS. It induces inflammation, renal cell growth, mitogenesis, apoptosis, migration, and differentiation. In addition, Ang II regulates the gene expression of bioactive substances and activates multiple intracellular signaling pathways that are involved in renal damage. Activation of the Ang II type 1 (AT1) receptor pathway results in the production of proinflammatory mediators, intracellular formation of reactive oxygen species, cell proliferation, and extracellular matrix synthesis, which in turn facilities renal injury. Involvement of angiotensinogen (AGT) in intrarenal RAS activation and development of renal disease has previously been reported. Moreover, studies have demonstrated that the urinary excretion rates of AGT provide a specific index of the intrarenal RAS status. Enhanced intrarenal AGT levels have been observed in experimental models of renal disease, supporting the concept that AGT plays an important role in the development and progression of renal disease. In this review, we focus on the role of intrarenal RAS activation in the pathophysiology of renal disease. Additionally, we explored the potential of urinary AGT as a novel biomarker of intrarenal RAS status in renal disease.

Impairment of K-Ras signaling networks and increased efficacy of epidermal growth factor receptor inhibitors by a novel synthetic miR-143.

PubMed

Akao, Yukihiro; Kumazaki, Minami; Shinohara, Haruka; Sugito, Nobuhiko; Kuranaga, Yuki; Tsujino, Takuya; Yoshikawa, Yuki; Kitade, Yukio

2018-05-01

Despite considerable research on K-Ras inhibitors, none had been established until now. We synthesized nuclease-resistant synthetic miR-143 (miR-143#12), which strongly silenced K-Ras, its effector signal molecules AKT and ERK, and the K-Ras activator Sos1. We examined the anti-proliferative effect of miR-143#12 and the mechanism in human colon cancer DLD-1 cell (G13D) and other cell types harboring K-Ras mutations. Cell growth was markedly suppressed in a concentration-dependent manner by miR-143#12 (IC 50 : 1.32 nmol L -1 ) with a decrease in the K-Ras mRNA level. Interestingly, this mRNA level was also downregulated by either a PI3K/AKT or MEK inhibitor, which indicates a positive circuit of K-Ras mRNA expression. MiR-143#12 silenced cytoplasmic K-Ras mRNA expression and impaired the positive circuit by directly targeting AKT and ERK mRNA. Combination treatment with miR-143#12 and a low-dose EGFR inhibitor induced a synergistic inhibition of growth with a marked inactivation of both PI3K/AKT and MAPK/ERK signaling pathways. However, silencing K-Ras by siR-KRas instead of miR-143#12 did not induce this synergism through the combined treatment with the EGFR inhibitor. Thus, miR-143#12 perturbed the K-Ras expression system and K-Ras activation by silencing Sos1 and, resultantly, restored the efficacy of the EGFR inhibitors. The in vivo results also supported those of the in vitro experiments. The extremely potent miR-143#12 enabled us to understand K-Ras signaling networks and shut them down by combination treatment with this miRNA and EGFR inhibitor in K-Ras-driven colon cancer cell lines. © 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Carboxyl methylation of Ras-related proteins during signal transduction in neutrophils.

PubMed

Philips, M R; Pillinger, M H; Staud, R; Volker, C; Rosenfeld, M G; Weissmann, G; Stock, J B

1993-02-12

In human neutrophils, as in other cell types, Ras-related guanosine triphosphate-binding proteins are directed toward their regulatory targets in membranes by a series of posttranslational modifications that include methyl esterification of a carboxyl-terminal prenylcysteine residue. In intact cells and in a reconstituted in vitro system, the amount of carboxyl methylation of Ras-related proteins increased in response to the chemoattractant N-formyl-methionyl-leucyl-phenylalanine (FMLP). Activation of Ras-related proteins by guanosine-5'-O-(3-thiotriphosphate) had a similar effect and induced translocation of p22rac2 from cytosol to plasma membrane. Inhibitors of prenylcysteine carboxyl methylation effectively blocked neutrophil responses to FMLP. These findings suggest a direct link between receptor-mediated signal transduction and the carboxyl methylation of Ras-related proteins.

Evaluation of in vitro anticancer activity of 1,8-Cineole-containing n-hexane extract of Callistemon citrinus (Curtis) Skeels plant and its apoptotic potential.

PubMed

Sampath, Sowndarya; Veeramani, Vidhya; Krishnakumar, Gopal Shankar; Sivalingam, Udhayakumar; Madurai, Suguna Lakshmi; Chellan, Rose

2017-09-01

Plants are the source of a variety of secondary metabolites, which are often used in the anticancer activity. Discovering new anticancer drug from herbal source is more important in both biological and pharmacological activities. Hence, the objective of this study is to identify the anticancer agent in Callistemon citrinus (Curtis) Skeels (CC) for the treatment of cancer. Very recently we have reported an increased antioxidant activity in the ethanolic and methanolic extracts (EE and ME) of CC but significantly reduced activity (rather increased cytotoxicity), in the n-hexane extract (HE). In this study, the cytotoxicity of all the three solvent extracts was tested against A431, MG-63 and HaCaT cell lines by MTT assay. Interestingly HE has showed increased anti-proliferative effect against the cancer cells but was resisted by non-malignant cells. HPLC and GC-MS analysis revealed the presence of 1,8-Cineole as a predominant compound in HE, the semi-purified bioactive extract. Henceforth, this would be called HE-C and be used for further analyses to understand its mode of action on induced apoptosis/necrosis. Alamar blue assay of HE-C showed cytotoxicity and change in morphological characteristics, which was confirmed by AO/EB staining using fluorescence microscopy, ultra-structural features of apoptosis using SEM and TEM. HE-C induced cell death was also detected by FACS using FITC-labelled Annexin-V and Propidium iodide. ROS generation was monitored using DCF-DA by flow cytometry. The overall results suggested that the selective extract (HE-C) containing 1,8-Cineole has shown potential anti-cancer activity in a dose-dependent manner, and cell death was induced through ROS-mediated apoptosis. Our findings provide an insight into the potential of 1,8-Cineole as a novel drug for killing cancer cells. Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Prototypes of self-powered radiation detectors employing intrinsic high-energy current.

PubMed

Zygmanski, Piotr; Shrestha, Suman; Briovio, Davide; Karellas, Andrew; Sajo, Erno

2016-01-01

The authors experimentally investigate the effect of direct energy conversion of x-rays via selfpowered Auger- and photocurrent, potentially suitable to practical radiation detection and dosimetry in medical applications. Experimental results are compared to computational predictions. The detector the authors consider is a thin-film multilayer device, composed of alternating disparate electrically conductive and insulating layers. This paper focuses on the experiments while a companion paper introduces the fundamental concepts of high-energy current (HEC) detectors. The energy of ionizing radiation is directly converted to detector signal via electric current induced by high-energy secondary electrons generated in the detector material by the incident primary radiation. The HEC electrons also ionize the dielectric and the resultant charge carriers are selfcollected due to the contact potential of the disparate electrodes. Thus, an electric current is induced in the conductors in two different ways without the need for externally applied bias voltage or amplification. Thus, generated signal in turn is digitized by a data acquisition system. To determine the fundamental properties of the HEC detector and to demonstrate its feasibility for medical applications, the authors used a planar geometry composed of multilayer microstructures. Various detectors with up to seven conducting layers with different combinations of materials (250 μm Al, 35 μm Cu, 100 μm Pb) and air gaps (100 μm) were exposed to nearly plane-parallel 60-120 kVp x-ray beams. For the experimental design and verification, the authors performed coupled electron-photon radiation transport computations. The detector signal was measured using a commercial data acquisition system with 24 bits dynamic range, 0.4 fC sensitivity, and 0.9 ms sampling time. Measured signals for the prototype detector varied depending on the number of layers, material type, and incident photon energy, and it was in the range of 30-150 nA/cm(2) for unit air kerma (1 Gy), which is viable for practical applications. The experiments had an excellent agreement with the computations. Within the examined range of 60-120 kVp, the energy dependence of the HEC (normalized to the x-ray tube output) was relatively small. Based on the experimental results for 100 ms sampling time, it would be possible to measure the time dependence of x-ray beams for x-ray tube current of 0.1 mA or higher. Significant advantages of the HEC device are that generation of its signal does not require external power supply, it can be made in any size and shape, including flexible curvilinear forms, and it is inexpensive. It remains to be determined, which of the potential applications in medical dosimetry (both in vivo and external), or radiation protection would benefit from such selfpowered detectors.

Frequencies and prognostic impact of RAS mutations in MLL-rearranged acute lymphoblastic leukemia in infants

PubMed Central

Driessen, Emma M.C.; van Roon, Eddy H.J.; Spijkers-Hagelstein, Jill A.P.; Schneider, Pauline; de Lorenzo, Paola; Valsecchi, Maria Grazia; Pieters, Rob; Stam, Ronald W.

2013-01-01

Acute lymphoblastic leukemia in infants represents an aggressive malignancy associated with a high incidence (approx. 80%) of translocations involving the Mixed Lineage Leukemia (MLL) gene. Attempts to mimic Mixed Lineage Leukemia fusion driven leukemogenesis in mice raised the question whether these fusion proteins require secondary hits. RAS mutations are suggested as candidates. Earlier results on the incidence of RAS mutations in Mixed Lineage Leukemia-rearranged acute lymphoblastic leukemia are inconclusive. Therefore, we studied frequencies and relation with clinical parameters of RAS mutations in a large cohort of infant acute lymphoblastic leukemia patients. Using conventional sequencing analysis, we screened neuroblastoma RAS viral (v-ras) oncogene homolog gene (NRAS), v-Ki-ras Kirsten rat sarcoma viral oncogene homolog gene (KRAS), and v-raf murine sarcoma viral oncogene homolog B1 gene (BRAF) for mutations in a large cohort (n=109) of infant acute lymphoblastic leukemia patients and studied the mutations in relation to several clinical parameters, and in relation to Homeobox gene A9 expression and the presence of ALL1 fused gene 4-Mixed Lineage Leukemia (AF4-MLL). Mutations were detected in approximately 14% of all cases, with a higher frequency of approximately 24% in t(4;11)-positive patients (P=0.04). Furthermore, we identified RAS mutations as an independent predictor (P=0.019) for poor outcome in Mixed Lineage Leukemia-rearranged infant acute lymphoblastic leukemia, with a hazard ratio of 3.194 (95% confidence interval (CI):1.211–8.429). Also, RAS-mutated infants have higher white blood cell counts at diagnosis (P=0.013), and are more resistant to glucocorticoids in vitro (P<0.05). Finally, we demonstrate that RAS mutations, and not the lack of Homeobox gene A9 expression nor the expression of AF4-MLL are associated with poor outcome in t(4;11)-rearranged infants. We conclude that the presence of RAS mutations in Mixed Lineage Leukemia-rearranged infant acute lymphoblastic leukemia is an independent predictor for a poor outcome. Therefore, future risk-stratification based on abnormal RAS-pathway activation and RAS-pathway inhibition could be beneficial in RAS-mutated infant acute lymphoblastic leukemia patients. PMID:23403319

Recurrent aphthous stomatitis: clinical characteristics and associated systemic disorders.

PubMed

Rogers, R S

1997-12-01

Recurrent aphthous stomatitis (RAS), commonly known as canker sores, has been reported as recurrent oral ulcers, recurrent aphthous ulcers, or simple or complex aphthosis. RAS is the most common inflammatory ulcerative condition of the oral mucosa in North American patients. One of its variants is the most painful condition of the oral mucosa. Recurrent aphthous stomatitis has been the subject of active investigation along multiple lines of research, including epidemiology, immunology, clinical correlations, and therapy. Clinical evaluation of the patient requires correct diagnosis of RAS and classification of the disease based on morphology (MiAU, MjAU, HU) and severity (simple versus complex). The natural history of individual lesions of RAS is important, because it is the bench mark against which treatment benefits are measured. The lesions of RAS are not caused by a single factor but occur in an environment that is permissive for development of lesions. These factors include trauma, smoking, stress, hormonal state, family history, food hypersensitivity and infectious or immunologic factors. The clinician should consider these elements of a multifactorial process leading to the development of lesions of RAS. To properly diagnose and treat a patient with lesions of RAS, the clinician must identify or exclude associated systemic disorders or "correctable causes." Behçet's disease and complex aphthosis variants, such as ulcus vulvae acutum, mouth and genital ulcers with inflamed cartilage (MAGIC) syndrome, fever, aphthosis, pharyngitis, and adenitis (FAPA) syndrome, and cyclic neutropenia, should be considered. The aphthous-like oral ulcerations of patients with human immunodeficiency virus (HIV) disease represent a challenging differential diagnosis. The association of lesions of RAS with hematinic deficiencies and gastrointestinal diseases provides an opportunity to identify a "correctable cause," which, with appropriate treatment, can result in a remission or substantial lessening of disease activity.

Assessment of insulin sensitivity by the hyperinsulinemic euglycemic clamp: Comparison with the spectral analysis of photoplethysmography.

PubMed

De Souza, Aglecio Luiz; Batista, Gisele Almeida; Alegre, Sarah Monte

2017-01-01

We compare spectral analysis of photoplethysmography (PTG) with insulin resistance measured by the hyperinsulinemic euglycemic clamp (HEC) technique. A total of 100 nondiabetic subjects, 43 men and 57 women aged 20-63years, 30 lean, 42 overweight and 28 obese were enrolled in the study. These patients underwent an examination with HEC, and an examination with the PTG spectral analysis and calculation of the PTG Total Power (PTG-TP). Receiver-operating characteristic (ROC) curves were constructed to determine the specificity and sensitivity of PTG-TP in the assessment of insulin resistance. There is a moderate correlation between insulin sensitivity (M-value) and PTG-TP (r=- 0.64, p<0.0001). The ROC curves showed that the most relevant cutoff to the whole study group was a PTG-TP>406.2. This cut-off had a sensitivity=95.7%, specificity =84,4% and the area under the ROC curve (AUC)=0.929 for identifying insulin resistance. All AUC ROC curve analysis were significant (p<0.0001). The use of the PTG-TP marker measured from the PTG spectral analysis is a useful tool in screening and follow up of IR, especially in large-scale studies. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Gender aspects in heart failure. Pathophysiology and medical therapy.

PubMed

Regitz-Zagrosek, V; Lehmkuhl, E; Lehmkuhl, H B; Hetzer, R

2004-09-01

Gender differences in the syndrome of heart failure (HF) occur in etiology and pathophysiology and lead to differences in the clinical presentation and course of the syndrome. In addition, gender specific treatment responses and gender associated differences in the behavior of treating physicians are found. Hypertension and diabetes play a major role as causes of HF in women and both interact in their pathophysiology with the renin angiotensin system (RAS). Modulation of the RAS by estrogens explains specific differences between pre- and post-menopausal women and men. Myocardial growth processes and myocardial calcium handling are differentially regulated in female and male myocytes. Myocardial remodeling with age and as a consequence of mechanical load differs in women and men. For yet unknown reasons, HF with preserved systolic function seems to be more frequent in women than in men and the clinical course of systolic HF is different in both genders. Medical therapy in heart failure has usually not been specified according to gender and gender specific analysis has been neglected in most large survival trials. Only a post-hoc analysis of gender differences led to the recognition of increased mortality with digitalis therapy in women. Single studies on angiotensin converting enzyme inhibitors (ACEI) or beta-receptor blockers did not reach significant end points in women whereas meta-analyses showed overall positive effects. Side effects of ACEI are more common and pharmacokinetics of beta-blockers are different in women. Angiotensin receptor blockers (ARB) are equally well tolerated in women and men. RAS inhibition may be particularly advantageous in postmenopausal women in whom the natural modulation of the RAS by estrogens is lost.

Base (100-year) flood elevations for selected sites in Livingston County, Missouri

USGS Publications Warehouse

Southard, Rodney E.; Richards, Joseph M.

2002-01-01

The primary criteria for community participation in the National Flood Insurance Program is the adoption and enforcement of floodplain management requirements that minimize the potential for flood damages to existing and proposed development in flood-hazard areas. This report provides base flood elevations (BFE) for a 100-year recurrence-interval flood for use in the management and regulation of 18 flood-hazard areas designated by the Federal Emergency Management Agency as approximate Zone A areas in Livingston County, Missouri. The one-dimensional surface-water flow models HEC-RAS and Water-Surface PROfile (WSPRO) were used to compute base (100-year) flood elevations for 18 Zone A sites. The HEC-RAS model was used at BFE sites 1 to 6, 9, 10, and 15 to 18. The WSPRO model was used at BFE sites 7, 8, and 11 to 14. The 18 sites are all located in Livingston County, Missouri, at U.S., State, or County road crossings, and the base flood elevation was determined at the upstream side of each crossing. The base (100-year) flood elevations for BFE 1, 2, and 3 on Shoal Creek at Dawn and Shoal Creek Drainage Ditch near Dawn are 701.0, 701.0, and 696.5 feet, respectively. The base (100-year) flood elevations for BFE 4 and 5 on Indian Branch near Sampsel and a tributary to Indian Branch near Sampsel are 711.7 and 755.4 feet, respectively. Site BFE 6 is located on Honey Creek near Farmersville and the base (100-year) flood elevation for this site is 730.8 feet. One site (BFE 7) is located on No Creek near Farmersville. The base (100-year) flood elevation for this site is 731.3 feet. Site BFE 8 is located on Crooked Creek near Chillicothe and the base (100-year) elevation is 716.4 feet. One site (BFE 9) is located on a tributary to Coon Creek at Chillicothe. The base (100-year) flood elevation for this site is 734.9 feet. Two sites (BFE 10 and 11) are located on Blackwell Branch at Chillicothe. The base (100-year) flood elevation for BFE 10 is 738.9 feet and for BFE 11 is 701.7 feet. The base (100-year) flood elevation for BFE 12 on Medicine Creek near Chula is 721.7 feet. Sites BFE 13 and 15 are on Muddy Creek and for BFE 14 is on Little Muddy Creek near Chula. The base (100-year) flood elevations for BFE 13 and 15 are 733.0 and 717.9 feet, respectively and for BFE 14 is 734.6 feet. Downstream from BFE 12 is site BFE 16 on Medicine Creek near Wheeling. The base (100-year) flood elevation for site BFE 16 is 686.1 feet. One site (BFE 17) is located on Campbell Creek near Bedford. The base (100-year) flood elevation at this site is 691.8 feet. Site BFE 18 is located on Towstring Creek near Hale. The base (100-year) flood elevation for site BFE 18 is 667.4 feet.

Reconstruction and modelling of the 1977 Glacial Lake Outburst Flood (GLOF) of the Engaño Lake, Chilean Patagonia.

NASA Astrophysics Data System (ADS)

Iribarren Anacona, Pablo; Norton, Kevin; Mackintosh, Andrew

2015-04-01

Floods from moraine-dammed lake failures can result in severe damage to mountain communities. GLOFs can also cause long-standing effects in riverine landscapes, due to the high intensity (i.e. great depth and high velocities) and long reach capacity of these events. GLOFs may increase in frequency as glaciers retreat and new lakes develop, highlighting the need for a better understanding of GLOF dynamics and the measures to reduce their negative outcomes. In Patagonia at least 16 moraine-dammed lakes have failed in historic time, however, data about GLOF dynamics and impacts are limited since GLOFs have mainly affected uninhabited areas and ungauged rivers. In March 1977, however, a GLOF flooded a small village (~130 inhabitants) in Chilean Patagonia. We reconstruct the dynamics of this event by semi-structured interviews, interpretation of satellite images (Landsat MSS) and two dimensional (2D) hydraulic modelling (using HEC-RAS 5.0 BETA and the SRTM v4 DEM). This reconstruction provides insights into GLOF behaviour, as well as the planning issues that led to socioeconomic consequences, which included relocation of the village. We mapped the flood extent and compiled data of flood depth and timing to constrain the 2D GLOF simulations. Modelling shows that the water released by the GLOF was in the order of 12-13 million cubic metres and that the flood reached Bahía Murta Viejo, located ~26 km from the failed lake, 2-3 hours after the moraine dam was breached. The flood lasted for about ten hours (at the village), although the peak discharge occurred after only one hour at this site. The maximum water depth at Bahía Murta Viejo was 1.5 m, however, water depths of up to 20 metres were simulated in upstream constricted reaches. The overall flood dynamics suggested by interviews and geomorphic mapping, including hydraulic ponding upstream of bedrock gorges, was well represented in the 2D simulations in spite of the coarse resolution (~80 m) of the DEM used. The simulated flood intensity and the damage to buildings reported by Bahía Murta inhabitants also showed a good correspondence. The Engaño Lake had several characteristics in common with other failed lakes in Patagonia. For example, it was dammed by a narrow and steep moraine, and the lake was in contact with a retreating glacier at the time of breaching. However, the GLOF hazard was not identified prior the 1977 flood. Thus, lack of awareness and planning amplified the negative socioeconomic consequences of the GLOF. The 1977 GLOF contributed to the village's gradual relocation to a higher and safer place a few kilometres from the original settlement. The Río Engaño GLOF shows the utility of the HEC-RAS 5.0 2D capabilities in GLOF modelling and illustrates a small-scale and short-distance migration as a coping strategy to a natural hazard which may increase in frequency as atmospheric temperature rise and glaciers retreat.

Renin-angiotensin system within the diabetic podocyte.

PubMed

Márquez, Eva; Riera, Marta; Pascual, Julio; Soler, María José

2015-01-01

Diabetic kidney disease is the leading cause of end-stage renal disease. Podocytes are differentiated cells necessary for the development and maintenance of the glomerular basement membrane and the capillary tufts, as well as the function of the glomerular filtration barrier. The epithelial glomerular cells express a local renin-angiotensin system (RAS) that varies in different pathological situations such as hyperglycemia or mechanical stress. RAS components have been shown to be altered in diabetic podocytopathy, and their modulation may modify diabetic nephropathy progression. Podocytes are a direct target for angiotensin II-mediated injury by altered expression and distribution of podocyte proteins. Furthermore, angiotensin II promotes podocyte injury indirectly by inducing cellular hypertrophy, increased apoptosis, and changes in the anionic charge of the glomerular basement membrane, among other effects. RAS blockade has been shown to decrease the level of proteinuria and delay the progression of chronic kidney disease. This review summarizes the local intraglomerular RAS and its imbalance in diabetic podocytopathy. A better understanding of the intrapodocyte RAS might provide a new approach for diabetic kidney disease treatment. Copyright © 2015 the American Physiological Society.

Defining the Collision Avoidance Region for DAA Systems

NASA Technical Reports Server (NTRS)

Thipphavong, David; Cone, Andrew; Park, Chunki; Lee, Seung Man; Santiago, Confesor

2016-01-01

Unmanned aircraft systems (UAS) will be required to equip with a detect-­-and-­-avoid (DAA) system in order to satisfy the federal aviation regulations to maintain well clear of other aircraft, some of which may be equipped with a Traffic Collision Avoidance System (TCAS) to mitigate the possibility of mid-­-air collisions. As such, the minimum operational performance standards (MOPS) for UAS DAA systems are being designed with TCAS interoperability in mind by a group of industry, government, and academic institutions named RTCA Special Committee-228 (SC-228). This document will discuss the development of the spatial-­-temporal volume known as the collision avoidance region in which the DAA system is not allowed to provide vertical guidance to maintain or regain DAA well clear that could conflict with resolution advisories (RAs) issued by the intruder aircraft's TCAS system. Three collision avoidance region definition candidates were developed based on the existing TCAS RA and DAA alerting definitions. They were evaluated against each other in terms of their interoperability with TCAS RAs and DAA alerts in an unmitigated factorial encounter analysis of 1.3 million simulated pairs.

Studying the Immunomodulatory Effects of Small Molecule Ras-Inhibitors in Animal Models of Rheumatoid Arthritis

DTIC Science & Technology

2015-10-01

Studying the Immunomodulatory Effects of Small Molecule Ras-Inhibitors in Animal Models of Rheumatoid Arthritis 5a. CONTRACT NUMBER 5b. GRANT NUMBER...Importantly, T cells from patients with Rheumatoid Arthritis (RA) display augmented activation of the Ras/Raf/MEK/ERK1/2 signaling pathway, and...analysis. The proposed project is highly relevant to the FY13 PRMRP topic area of Rheumatoid Arthritis (RA). The short-term impact of our research will

Alphavirus production is inhibited in neurofibromin 1-deficient cells through activated RAS signalling

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

Kolokoltsova, Olga A.; Domina, Aaron M.; Kolokoltsov, Andrey A.

2008-07-20

Virus-host interactions essential for alphavirus pathogenesis are poorly understood. To address this shortcoming, we coupled retrovirus insertional mutagenesis and a cell survival selection strategy to generate clonal cell lines broadly resistant to Sindbis virus (SINV) and other alphaviruses. Resistant cells had significantly impaired SINV production relative to wild-type (WT) cells, although virus binding and fusion events were similar in both sets of cells. Analysis of the retroviral integration sites identified the neurofibromin 1 (NF1) gene as disrupted in alphavirus-resistant cell lines. Subsequent analysis indicated that expression of NF1 was significantly reduced in alphavirus-resistant cells. Importantly, independent down-regulation of NF1 expressionmore » in WT HEK 293 cells decreased virus production and increased cell viability during SINV infection, relative to infected WT cells. Additionally, we observed hyperactive RAS signalling in the resistant HEK 293 cells, which was anticipated because NF1 is a negative regulator of RAS. Expression of constitutively active RAS (HRAS-G12V) in a WT HEK 293 cell line resulted in a marked delay in virus production, compared with infected cells transfected with parental plasmid or dominant-negative RAS (HRAS-S17N). This work highlights novel host cell determinants required for alphavirus pathogenesis and suggests that RAS signalling may play an important role in neuronal susceptibility to SINV infection.« less

RAS mutation status predicts survival and patterns of recurrence in patients undergoing hepatectomy for colorectal liver metastases.

PubMed

Vauthey, Jean-Nicolas; Zimmitti, Giuseppe; Kopetz, Scott E; Shindoh, Junichi; Chen, Su S; Andreou, Andreas; Curley, Steven A; Aloia, Thomas A; Maru, Dipen M

2013-10-01

To determine the impact of RAS mutation status on survival and patterns of recurrence in patients undergoing curative resection of colorectal liver metastases (CLM) after preoperative modern chemotherapy. RAS mutation has been reported to be associated with aggressive tumor biology. However, the effect of RAS mutation on survival and patterns of recurrence after resection of CLM remains unclear. Somatic mutations were analyzed using mass spectroscopy in 193 patients who underwent single-regimen modern chemotherapy before resection of CLM. The relationship between RAS mutation status and survival outcomes was investigated. Detected somatic mutations included RAS (KRAS/NRAS) in 34 (18%), PIK3CA in 13 (7%), and BRAF in 2 (1%) patients. At a median follow-up of 33 months, 3-year overall survival (OS) rates were 81% in patients with wild-type versus 52.2% in patients with mutant RAS (P = 0.002); 3-year recurrence-free survival (RFS) rates were 33.5% with wild-type versus 13.5% with mutant RAS (P = 0.001). Liver and lung recurrences were observed in 89 and 83 patients, respectively. Patients with RAS mutation had a lower 3-year lung RFS rate (34.6% vs 59.3%, P < 0.001) but not a lower 3-year liver RFS rate (43.8% vs 50.2%, P = 0.181). In multivariate analyses, RAS mutation predicted worse OS [hazard ratio (HR) = 2.3, P = 0.002), overall RFS (HR = 1.9, P = 0.005), and lung RFS (HR = 2.0, P = 0.01), but not liver RFS (P = 0.181). RAS mutation predicts early lung recurrence and worse survival after curative resection of CLM. This information may be used to individualize systemic and local tumor-directed therapies and follow-up strategies.

RAS mutation status predicts survival and patterns of recurrence in patients undergoing hepatectomy for colorectal liver metastases

PubMed Central

Vauthey, Jean-Nicolas; Zimmitti, Giuseppe; Kopetz, Scott E.; Shindoh, Junichi; Chen, Su S.; Andreou, Andreas; Curley, Steven A.; Aloia, Thomas A.; Maru, Dipen M.

2013-01-01

Objective To determine the impact of RAS mutation status on survival and patterns of recurrence in patients undergoing curative resection of colorectal liver metastases (CLM) after preoperative modern chemotherapy. Summary Background Data RAS mutation has been reported to be associated with aggressive tumor biology. However, the effect of RAS mutation on survival and patterns of recurrence after resection of CLM remains unclear. Methods Somatic mutations were analyzed using mass spectroscopy in 193 patients who underwent single-regimen modern chemotherapy before resection of CLM. The relationship between RAS mutation status and survival outcomes was investigated. Results Detected somatic mutations included RAS (KRAS/NRAS) in 34 patients (18%), PIK3CA in 13 (7%), and BRAF in 2 (1%). At a median follow-up of 33 months, 3-year overall survival (OS) rates were 81% in patients with wild-type vs 52.2% in patients with mutant RAS (P=0.002); 3-year recurrence-free survival (RFS) rates were 33.5% with wild-type vs 13.5% with mutant RAS (P=0.001). Liver and lung recurrences were observed in 89 and 83 patients, respectively. Patients with RAS mutation had a lower 3-year lung RFS rate (34.6% vs 59.3%, P<0.001), but not a lower 3-year liver RFS rate (43.8% vs 50.2%, P=0.181). In multivariate analyses, RAS mutation predicted worse OS (hazard ratio [HR] 2.3, P=0.002), overall RFS (HR 1.9, P=0.005), and lung RFS (HR 2.0, P=0.01), but not liver RFS (P=0.181). Conclusions RAS mutation predicts early lung recurrence and worse survival after curative resection of CLM. This information may be used to individualize systemic and local tumor-directed therapies and follow-up strategies. PMID:24018645

Long-term follow-up of chronic pancreatitis patients with K-ras mutation in the pancreatic juice.

PubMed

Kamisawa, Terumi; Takuma, Kensuke; Tabata, Taku; Egawa, Naoto; Yamaguchi, Toshikazu

2011-01-01

Pancreatic cancer is known to occur during the course of chronic pancreatitis in some patients. This study aimed to identify a high risk group for developing pancreatic cancer associated with chronic pancreatitis, particularly the presence of K-ras mutations in the pancreatic juice. K-ras mutation was analyzed by enriched polymerase chain reaction-enzyme linked mini-sequence assay in endoscopically-collected pancreatic juice of 21 patients with chronic pancreatitis between 1995 and 2000. All of them were followed-up for 6.0 +/- 3.8 (mean +/- SD) years (range, 2.1-14.2 years). K-ras point mutation was observed in the pancreatic juice of 11 patients with chronic pancreatitis (2+, n=2; 1+, n=6; +/-, n=3). Of these, 2 chronic pancreatitis patients with 2+K-ras point mutation developed pancreatic cancer 4.5 and 10.8 years, respectively, after the examination. Two chronic pancreatitis patients with K-ras mutation developed pancreatic cancer 4.5 and 10.8 years later. Semiquantitative analysis of K-ras mutation in endoscopically-collected pancreatic juice appears to be a useful tool for identifying chronic pancreatitis patients at high risk for developing pancreatic cancer.

The Ras effector RASSF2 is a novel tumor-suppressor gene in human colorectal cancer.

PubMed

Akino, Kimishige; Toyota, Minoru; Suzuki, Hiromu; Mita, Hiroaki; Sasaki, Yasushi; Ohe-Toyota, Mutsumi; Issa, Jean-Pierre J; Hinoda, Yuji; Imai, Kohzoh; Tokino, Takashi

2005-07-01

Activation of Ras signaling is a hallmark of colorectal cancer (CRC), but the roles of negative regulators of Ras are not fully understood. Our aim was to address that question by surveying genetic and epigenetic alterations of Ras-Ras effector genes in CRC cells. The expression and methylation status of 6 RASSF family genes were examined using RT-PCR and bisulfite PCR in CRC cell lines and in primary CRCs and colorectal adenomas. Colony formation assays and flow cytometry were used to assess the tumor suppressor activities of RASSF1 and RASSF2. Immunofluorescence microscopy was used to determine the effect of altered RASSF2 expression on cell morphology. Mutations of K- ras , BRAF, and p53 were identified using single-strand conformation analysis and direct sequencing. Aberrant methylation and histone deacetylation of RASSF2 was associated with the gene's silencing in CRC. The activities of RASSF2, which were distinct from those of RASSF1, included induction of morphologic changes and apoptosis; moreover, its ability to prevent cell transformation suggests that RASSF2 acts as a tumor suppressor in CRC. Primary CRCs that showed K- ras /BRAF mutations also frequently showed RASSF2 methylation, and inactivation of RASSF2 enhanced K- ras -induced oncogenic transformation. RASSF2 methylation was also frequently identified in colorectal adenomas. RASSF2 is a novel tumor suppressor gene that regulates Ras signaling and plays a pivotal role in the early stages of colorectal tumorigenesis.

Evolution and Diversity of the Ras Superfamily of Small GTPases in Prokaryotes

PubMed Central

Wuichet, Kristin; Søgaard-Andersen, Lotte

2015-01-01

The Ras superfamily of small GTPases are single domain nucleotide-dependent molecular switches that act as highly tuned regulators of complex signal transduction pathways. Originally identified in eukaryotes for their roles in fundamental cellular processes including proliferation, motility, polarity, nuclear transport, and vesicle transport, recent studies have revealed that single domain GTPases also control complex functions such as cell polarity, motility, predation, development and antibiotic resistance in bacteria. Here, we used a computational genomics approach to understand the abundance, diversity, and evolution of small GTPases in prokaryotes. We collected 520 small GTPase sequences present in 17% of 1,611 prokaryotic genomes analyzed that cover diverse lineages. We identified two discrete families of small GTPases in prokaryotes that show evidence of three distinct catalytic mechanisms. The MglA family includes MglA homologs, which are typically associated with the MglB GTPase activating protein, whereas members of the Rup (Ras superfamily GTPase of unknown function in prokaryotes) family are not predicted to interact with MglB homologs. System classification and genome context analyses support the involvement of small GTPases in diverse prokaryotic signal transduction pathways including two component systems, laying the foundation for future experimental characterization of these proteins. Phylogenetic analysis of prokaryotic and eukaryotic GTPases supports that the last universal common ancestor contained ancestral MglA and Rup family members. We propose that the MglA family was lost from the ancestral eukaryote and that the Ras superfamily members in extant eukaryotes are the result of vertical and horizontal gene transfer events of ancestral Rup GTPases. PMID:25480683

Combined use of drugs inhibiting the renin-angiotensin system: prescribing patterns and risk of acute kidney injury in German nursing home residents.

PubMed

Dörks, Michael; Herget-Rosenthal, Stefan; Hoffmann, Falk; Jobski, Kathrin

2018-01-01

In 2012, the European Medicines Agency reviewed the safety of dual renin-angiotensin system (RAS) blockade because of potentially increased risks for inter alia acute kidney injury (AKI). Since residents of nursing homes are particularly vulnerable to adverse drug outcomes, the aims of our study were to describe RAS-inhibiting drug use in German nursing home residents and examine the risk of AKI associated with dual RAS blockade. Based on claims data, a nested case-control study within a cohort of RAS-inhibiting drug users was conducted. Using conditional logistic regression, confounder-adjusted odds ratios (aORs) and 95% confidence intervals (CI) were obtained for the risk of AKI associated with dual RAS blockade. Subgroup analyses were performed in patients with diabetes or chronic kidney disease and both comorbidities. Of all 127,227 nursing home residents, the study cohort included 64,567 (50.7%) who were treated with at least one RAS-inhibiting drug. More than three quarters of the study population were female (77.1%). Mean age was 86.0 ± 6.8 years. Most residents were treated with angiotensin-converting enzyme inhibitors (77.8%), followed by angiotensin II receptor blockers (21.6%) and aliskiren (0.2%). Annual prevalence of dual RAS blockade declined from 9.6 (95% CI 7.8-11.8) in 2010 to 4.7 (95% CI 4.0-5.4) per 1,000 users in 2014. In the overall cohort, AKI was not significantly associated with dual RAS blockade (aOR 1.99; 0.77-5.17). However, significantly increased aORs were observed when considering patients with diabetes (3.47; 1.27-9.47), chronic kidney disease (4.74; 1.24-18.13) or both (11.17; 2.65-47.15). Prescribing of drugs inhibiting the RAS is common in German nursing homes. Though the prevalence of dual RAS blockade declined, our study showed an increased risk of AKI in patients with diabetes and/or chronic kidney disease. Therefore, cautious use is warranted in these vulnerable patients.

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

Murphy, Lynea A.; Moore, Tanya; Nesnow, Stephen, E-mail: nesnow.stephen@epa.gov

Propiconazole is a mouse hepatotumorigenic fungicide designed to inhibit CYP51, a key enzyme in the biosynthesis of ergosterol in fungi and is widely used in agriculture to prevent fungal growth. Metabolomic studies in mice revealed that propiconazole increased levels of hepatic cholesterol metabolites and bile acids, and transcriptomic studies revealed that genes within the cholesterol biosynthesis, cholesterol metabolism and bile acid biosyntheses pathways were up-regulated. Hepatic cell proliferation was also increased by propiconazole. AML12 immortalized hepatocytes were used to study propiconazole's effects on cell proliferation focusing on the dysregulation of cholesterol biosynthesis and resulting effects on Ras farnesylation and Erk1/2more » activation as a primary pathway. Mevalonate, a key intermediate in the cholesterol biosynthesis pathway, increases cell proliferation in several cancer cell lines and tumors in vivo and serves as the precursor for isoprenoids (e.g. farnesyl pyrophosphate) which are crucial in the farnesylation of the Ras protein by farnesyl transferase. Farnesylation targets Ras to the cell membrane where it is involved in signal transduction, including the mitogen-activated protein kinase (MAPK) pathway. In our studies, mevalonic acid lactone (MVAL), a source of mevalonic acid, increased cell proliferation in AML12 cells which was reduced by farnesyl transferase inhibitors (L-744,832 or manumycin) or simvastatin, an HMG-CoA reductase inhibitor, indicating that this cell system responded to alterations in the cholesterol biosynthesis pathway. Cell proliferation in AML12 cells was increased by propiconazole which was reversed by co-incubation with L-744,832 or simvastatin. Increasing concentrations of exogenous cholesterol muted the proliferative effects of propiconazole and the inhibitory effects of L-733,832, results ascribed to reduced stimulation of the endogenous cholesterol biosynthesis pathway. Western blot analysis of subcellular fractions from control, MVAL or propiconazole-treated cells revealed increased Ras protein in the cytoplasmic fraction of L-744,832-treated cells, while propiconazole or MVAL reversed these effects. Western blot analysis indicated that phosphorylation of Erk1/2, a protein downstream of Ras, was increased by propiconazole. These data indicate that propiconazole increases cell proliferation by increasing the levels of cholesterol biosynthesis intermediates presumably through a negative feedback mechanism within the pathway, a result of CYP51 inhibition. This feedback mechanism increases Erk1/2 signaling through mevalonate-mediated Ras activation. These results provide an explanation for the observed effects of propiconazole on hepatic cholesterol pathways and on the increased hepatic cell proliferation induced by propiconazole in mice. Highlights: ► Propiconazole increases cell proliferation in AML12 mouse hepatocytes. ► Propiconazole increases Ras farnesylation and alters Ras membrane localization. ► Propiconazole increases Erk1/2 phosphorylation. ► Dysregulation of the cholesterol biosynthesis pathway can explain these results. ► These results can explain similar effects induced by propiconazole in mice.« less

Analysis of factors causing hyperkalemia.

PubMed

Takaichi, Kenmei; Takemoto, Fumi; Ubara, Yoshifumi; Mori, Yasumichi

2007-01-01

Patients with impaired renal function or diabetes are considered to be prone to hyperkalemia. Furthermore, hyperkalemia is an adverse drug reaction of inhibitors of the renin-angiotensin system (RAS) that are established to be efficacious in these patients. However, the current status of hyperkalemia in the clinical setting remains obscure. A total of 9,117 patients treated at Toranomon Hospital between January and October 2005, who had serum creatinine levels below 5 mg/dL were studied. Patients on dialysis and patients using cation exchange resin or diuretics that lower serum potassium were excluded. Serum potassium increased significantly accompanying the increase in serum creatinine, and was significantly elevated in diabetic patients compared to non-diabetic patients. Serum potassium also increased significantly with the administration of angiotensin-II receptor blockers (ARB), angiotensin-converting-enzyme inhibitors (ACEI) or beta-blockers. A combination of diabetes and RAS inhibitor administration significantly increased serum potassium compared to each factor alone in patients with a serum creatinine level below 1.5 mg/dL but not in those with a higher serum creatinine level. According to step-wise multiple regression analyses, an elevated serum creatinine level had the strongest positive correlation with the serum potassium level, followed by diabetes, ACEI use, ARB use, and age. Lowered renal function, diabetes, use of RAS inhibitors and old age are independent factors that increase the serum potassium level. Caution should be exercised when using RAS inhibitors in diabetic patients even if their renal function is relatively preserved. In selected patients with diabetes or impaired renal function, however, RAS inhibitors can be used without hyperkalemia.

Plasma concentrations and subcutaneous adipose tissue mRNA expression of clusterin in obesity and type 2 diabetes mellitus: the effect of short-term hyperinsulinemia, very-low-calorie diet and bariatric surgery.

PubMed

Kloučková, J; Lacinová, Z; Kaválková, P; Trachta, P; Kasalický, M; Haluzíková, D; Mráz, M; Haluzík, M

2016-07-18

Clusterin is a heterodimeric glycoprotein with wide range of functions. To further explore its possible regulatory role in energy homeostasis and in adipose tissue, we measured plasma clusterin and its mRNA expression in subcutaneous adipose tissue (SCAT) of 15 healthy lean women, 15 obese women (OB) and 15 obese women with type 2 diabetes mellitus (T2DM) who underwent a 2-week very low-calorie diet (VLCD), 10 obese women without T2DM who underwent laparoscopic sleeve gastrectomy (LSG) and 8 patients with T2DM, 8 patients with impaired glucose tolerance (IGT) and 8 normoglycemic patients who underwent hyperinsulinemic euglycemic clamp (HEC). VLCD decreased plasma clusterin in OB but not in T2DM patients while LSG and HEC had no effect. Clusterin mRNA expression in SCAT at baseline was increased in OB and T2DM patients compared with controls. Clusterin mRNA expression decreased 6 months after LSG and remained decreased 12 months after LSG. mRNA expression of clusterin was elevated at the end of HEC compared with baseline only in normoglycemic but not in IGT or T2DM patients. In summary, our data suggest a possible local regulatory role for clusterin in the adipose tissue rather than its systemic involvement in the regulation of energy homeostasis.

Air Emission Reduction Benefits of Biogas Electricity Generation at Municipal Wastewater Treatment Plants.

PubMed

Gingerich, Daniel B; Mauter, Meagan S

2018-02-06

Conventional processes for municipal wastewater treatment facilities are energy and materially intensive. This work quantifies the air emission implications of energy consumption, chemical use, and direct pollutant release at municipal wastewater treatment facilities across the U.S. and assesses the potential to avoid these damages by generating electricity and heat from the combustion of biogas produced during anaerobic sludge digestion. We find that embedded and on-site air emissions from municipal wastewater treatment imposed human health, environmental, and climate (HEC) damages on the order of $1.63 billion USD in 2012, with 85% of these damages attributed to the estimated consumption of 19 500 GWh of electricity by treatment processes annually, or 0.53% of the US electricity demand. An additional 11.8 million tons of biogenic CO 2 are directly emitted by wastewater treatment and sludge digestion processes currently installed at plants. Retrofitting existing wastewater treatment facilities with anaerobic sludge digestion for biogas production and biogas-fueled heat and electricity generation has the potential to reduce HEC damages by up to 24.9% relative to baseline emissions. Retrofitting only large plants (>5 MGD), where biogas generation is more likely to be economically viable, would generate HEC benefits of $254 annually. These findings reinforce the importance of accounting for use-phase embedded air emissions and spatially resolved marginal damage estimates when designing sustainable infrastructure systems.

Drug discovery in renin-angiotensin system intervention: past and future.

PubMed

Williams, Bryan

2016-06-01

The renin-angiotensin system (RAS) plays a central role in the control of blood pressure in the body and the way this interacts with other systems is widely recognized. This has not always been the case and this review summarizes how our knowledge has evolved from the initial discovery of renin by Tigerstedt and Berman in 1898. This includes the identification of angiotensin in the 1950s to the proposed relationship between this system, hypertension and ultimately cardiovascular disease. While the RAS is far more complex than originally thought, much is now known about this system and the wide ranging effects of angiotensin in the body. This has enabled the development of therapies that target the various proteins in this pathway and hence are implicated in disease. The first of these treatments was the angiotensin converting enzyme inhibitors (ACE-Is), followed by the angiotensin receptor blockers (ARBs), and more recently the direct renin inhibitors (DRIs). Clinical outcome trials have shown these drugs to be effective, but as they act at contrasting points in the RAS, there are differences in their efficacy and safety profiles. RAS blockade is the foundation of modern combination therapy with a calcium channel blocker and/or a diuretic given to reduce blood pressure and limit the impact of RAS activation. Other options that complement these treatments may be available in the future and will offer more choice to clinicians. © The Author(s), 2016.

[Farnesyl transferase inhibitors (anti-Ras). A new class of anticancer agents].

PubMed

Levy, R

Ras genes are frequently activated in human tumours. The role of their product, the P21 proteins, in the transduction of the mitogenic signal makes them attractive targets for an anti-neoplastic therapy. The p21 ras proteins are linked to the plasma membrane and transformed into an active form for signal transmission. Their effect is to mediate the effects of growth factors. Two drug families, the Benzodiazepine peptidomimetics and the CAAX tetrapeptides which inhibit the farnesylation of P21-Ras proteins abolish the transforming properties of mutated P21. These promising drugs could rapidly have clinical applications. They have been shown to be highly active at precise concentrations on ras-transformed cells but at the same concentrations are not toxic for untransformed cells. They do not effect other similar enzyme systems within the cell, underlining their selective capacity. Theoretically anti-ras therapy could only suspend cell transformation although it might be possible that if given long enough, a lethal threshold could be reached.

Uncertainty estimation of water levels for the Mitch flood event in Tegucigalpa

NASA Astrophysics Data System (ADS)

Fuentes Andino, D. C.; Halldin, S.; Lundin, L.; Xu, C.

2012-12-01

Hurricane Mitch in 1998 left a devastating flood in Tegucigalpa, the capital city of Honduras. Simulation of elevated water surfaces provides a good way to understand the hydraulic mechanism of large flood events. In this study the one-dimensional HEC-RAS model for steady flow conditions together with the two-dimensional Lisflood-fp model were used to estimate the water level for the Mitch event in the river reaches at Tegucigalpa. Parameters uncertainty of the model was investigated using the generalized likelihood uncertainty estimation (GLUE) framework. Because of the extremely large magnitude of the Mitch flood, no hydrometric measurements were taken during the event. However, post-event indirect measurements of discharge and observed water levels were obtained in previous works by JICA and USGS. To overcome the problem of lacking direct hydrometric measurement data, uncertainty in the discharge was estimated. Both models could well define the value for channel roughness, though more dispersion resulted from the floodplain value. Analysis of the data interaction showed that there was a tradeoff between discharge at the outlet and floodplain roughness for the 1D model. The estimated discharge range at the outlet of the study area encompassed the value indirectly estimated by JICA, however the indirect method used by the USGS overestimated the value. If behavioral parameter sets can well reproduce water surface levels for past events such as Mitch, more reliable predictions for future events can be expected. The results acquired in this research will provide guidelines to deal with the problem of modeling past floods when no direct data was measured during the event, and to predict future large events taking uncertainty into account. The obtained range of the uncertain flood extension will be an outcome useful for decision makers.

Development of Urban Inundation Warning Model at Cyclic Artificial Water Way in Song-do International City, Republic of Korea

NASA Astrophysics Data System (ADS)

Lee, T.; Lee, C.; Kim, H.

2016-12-01

Abstract Song-do international city was constructed by reclaiming land from the coastal waters of Yeonsu-gu, Incheon Metropolitan City, Republic of Korea. The □-shaped cyclic artificial water way has been considered for improving water quality, waterfront and internal drainage in Song-do international city. By improving water quality, various marine facilities, such as marina, artificial beach, marine terminal, and so on, will be set up around the artificial water way for the waterfront. Since the water stage of the artificial water way changes depending on water gates operations, it is necessary to develop an urban inundation warning model to evaluate safeties of the waterfront facilities and its passengers. By considering characteristics of urban watershed, we calculate discharge flowing into the water way using XP-SWMM model. As a result of estimating 100-year flood frequency, although there are slight differences in drainage sections, the maximum flood discharge occurs in 90-min rainfall duration. In order to consider impacts of tide and hydraulic structure, we establish Inland drainage plans through the analysis of unsteady flow using HEC-RAS. The urban inundation warning model is configured to issue a warning when the water plain elevation exceeds EL. 1.5m which is usually managed at EL. 1.0m. In this study, the design flood stage of artificial water way and urban inundation warning model are developed for Song-do international city, and therefore it is expected that a reliability of management and operation of the waterfront facilities is improved. Keywords : Artificial Water Way; Waterfront; Urban Inundation Warning Model. Acknowlegement This research was supported by a grant [MPSS-NH-2015-79] through the Disaster and Safety Management Institute funded by Ministry of Public Safety and Security of Korean government.