Northwest Open Automated Demand Response Technology Demonstration Project

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

Kiliccote, Sila; Piette, Mary Ann; Dudley, Junqiao

The Lawrence Berkeley National Laboratory (LBNL) Demand Response Research Center (DRRC) demonstrated and evaluated open automated demand response (OpenADR) communication infrastructure to reduce winter morning and summer afternoon peak electricity demand in commercial buildings the Seattle area. LBNL performed this demonstration for the Bonneville Power Administration (BPA) in the Seattle City Light (SCL) service territory at five sites: Seattle Municipal Tower, Seattle University, McKinstry, and two Target stores. This report describes the process and results of the demonstration. OpenADR is an information exchange model that uses a client-server architecture to automate demand-response (DR) programs. These field tests evaluated the feasibilitymore » of deploying fully automated DR during both winter and summer peak periods. DR savings were evaluated for several building systems and control strategies. This project studied DR during hot summer afternoons and cold winter mornings, both periods when electricity demand is typically high. This is the DRRC project team's first experience using automation for year-round DR resources and evaluating the flexibility of commercial buildings end-use loads to participate in DR in dual-peaking climates. The lessons learned contribute to understanding end-use loads that are suitable for dispatch at different times of the year. The project was funded by BPA and SCL. BPA is a U.S. Department of Energy agency headquartered in Portland, Oregon and serving the Pacific Northwest. BPA operates an electricity transmission system and markets wholesale electrical power at cost from federal dams, one non-federal nuclear plant, and other non-federal hydroelectric and wind energy generation facilities. Created by the citizens of Seattle in 1902, SCL is the second-largest municipal utility in America. SCL purchases approximately 40% of its electricity and the majority of its transmission from BPA through a preference contract. SCL also provides ancillary services within its own balancing authority. The relationship between BPA and SCL creates a unique opportunity to create DR programs that address both BPA's and SCL's markets simultaneously. Although simultaneously addressing both market could significantly increase the value of DR programs for BPA, SCL, and the end user, establishing program parameters that maximize this value is challenging because of complex contractual arrangements and the absence of a central Independent System Operator or Regional Transmission Organization in the northwest.« less

Demand response, behind-the-meter generation and air quality.

PubMed

Zhang, Xiyue; Zhang, K Max

2015-02-03

We investigated the implications of behind-the-meter (BTM) generation participating in demand response (DR) programs. Specifically, we evaluated the impacts of NOx emissions from BTM generators enrolled in the New York Independent System Operator (NYISO)'s reliability-based DR programs. Through analyzing the DR program enrollment data, DR event records, ozone air quality monitoring data, and emission characteristics of the generators, we found that the emissions from BTM generators very likely contribute to exceedingly high ozone concentrations in the Northeast Corridor region, and very likely account for a substantial fraction of total NOx emissions from electricity generation. In addition, a companion study showed that the emissions from BTM generators could also form near-source particulate matter (PM) hotspots. The important policy implications are that the absence of up-to-date regulations on BTM generators may offset the current efforts to reduce the emissions from peaking power plants, and that there is a need to quantify the environmental impacts of DR programs in designing sound policies related to demand-side resources. Furthermore, we proposed the concept of "Green" DR resources, referring to those that not only provide power systems reliability services, but also have verifiable environmental benefits or minimal negative environmental impacts. We argue that Green DR resources that are able to maintain resource adequacy and reduce emissions at the same time are key to achieving the cobenefits of power system reliability and protecting public health during periods with peak electricity demand.

Demand Response Availability Profiles for California in the Year 2020

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

Olsen, Daniel; Sohn, Michael; Piette, Mary Ann

2014-11-01

Demand response (DR) is being considered as a valuable resource for keeping the electrical grid stable and efficient, and deferring upgrades to generation, transmission, and distribution systems. However, simulations to determine how much infrastructure upgrades can be deferred are necessary in order to plan optimally. Production cost modeling is a technique, which simulates the dispatch of generators to meet demand and reserves in each hour of the year, at minimal cost. By integrating demand response resources into a production cost model (PCM), their value to the grid can be estimated and used to inform operations and infrastructure planning. DR availabilitymore » profiles and constraints for 13 end-uses in California for the year 2020 were developed by Lawrence Berkeley National Laboratory (LBNL), and integrated into a production cost model by Lawrence Livermore National Laboratory (LLNL), for the California Energy Commission’s Value of Energy Storage and Demand Response for Renewable Integration in California Study. This report summarizes the process for developing the DR availability profiles for California, and their aggregate capabilities. While LBNL provided potential DR hourly profiles for regulation product in the ancillary services market and five-minute load following product in the energy market for LLNL’s study, additional results in contingency reserves and an assumed flexible product are also defined. These additional products are included in the analysis for managing high ramps associated with renewable generation and capacity products and they are also presented in this report.« less

Comparison of particle swarm optimization and differential evolution for aggregators' profit maximization in the demand response system

NASA Astrophysics Data System (ADS)

Wisittipanit, Nuttachat; Wisittipanich, Warisa

2018-07-01

Demand response (DR) refers to changes in the electricity use patterns of end-users in response to incentive payment designed to prompt lower electricity use during peak periods. Typically, there are three players in the DR system: an electric utility operator, a set of aggregators and a set of end-users. The DR model used in this study aims to minimize the operator's operational cost and offer rewards to aggregators, while profit-maximizing aggregators compete to sell DR services to the operator and provide compensation to end-users for altering their consumption profiles. This article presents the first application of two metaheuristics in the DR system: particle swarm optimization (PSO) and differential evolution (DE). The objective is to optimize the incentive payments during various periods to satisfy all stakeholders. The results show that DE significantly outperforms PSO, since it can attain better compensation rates, lower operational costs and higher aggregator profits.

Optimizing Industrial Consumer Demand Response Through Disaggregation, Hour-Ahead Pricing, and Momentary Autonomous Control

NASA Astrophysics Data System (ADS)

Abdulaal, Ahmed

The work in this study addresses the current limitations of the price-driven demand response (DR) approach. Mainly, the dependability on consumers to respond in an energy aware conduct, the response timeliness, the difficulty of applying DR in a busy industrial environment, and the problem of load synchronization are of utmost concern. In order to conduct a simulation study, realistic price simulation model and consumers' building load models are created using real data. DR action is optimized using an autonomous control method, which eliminates the dependency on frequent consumer engagement. Since load scheduling and long-term planning approaches are infeasible in the industrial environment, the proposed method utilizes instantaneous DR in response to hour-ahead price signals (RTP-HA). Preliminary simulation results concluded savings at the consumer-side at the cost of increased supplier-side burden due to the aggregate effect of the universal DR policies. Therefore, a consumer disaggregation strategy is briefly discussed. Finally, a refined discrete-continuous control system is presented, which utilizes multi-objective Pareto optimization, evolutionary programming, utility functions, and bidirectional loads. Demonstrated through a virtual testbed fit with real data, the new system achieves momentary optimized DR in real-time while maximizing the consumer's wellbeing.

2015 California Demand Response Potential Study - Charting California’s Demand Response Future. Interim Report on Phase 1 Results

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

Alstone, Peter; Potter, Jennifer; Piette, Mary Ann

Demand response (DR) is an important resource for keeping the electricity grid stable and efficient; deferring upgrades to generation, transmission, and distribution systems; and providing other customer economic benefits. This study estimates the potential size and cost of the available DR resource for California’s three investor-owned utilities (IOUs), as the California Public Utilities Commission (CPUC) evaluates how to enhance the role of DR in meeting California’s resource planning needs and operational requirements. As the state forges a clean energy future, the contributions of wind and solar electricity from centralized and distributed generation will fundamentally change the power grid’s operational dynamics.more » This transition requires careful planning to ensure sufficient capacity is available with the right characteristics – flexibility and fast response – to meet reliability needs. Illustrated is a snapshot of how net load (the difference between demand and intermittent renewables) is expected to shift. Increasing contributions from renewable generation introduces steeper ramps and a shift, into the evening, of the hours that drive capacity needs. These hours of peak capacity need are indicated by the black dots on the plots. Ultimately this study quantifies the ability and the cost of using DR resources to help meet the capacity need at these forecasted critical hours in the state.« less

Automated Demand Response for Energy Sustainability

DTIC Science & Technology

2015-05-01

project’s stated performance objectives. Emerging opportunities to participate in wholesale electricity markets can provide important economic, energy, and...Response in Wholesale Electricity Markets ..................................................... 7 Figure 5. Demand Bidding Communication and Control...resource in response to market or reliability conditions Demand Bidding Program DR programs that encourage customers to bid into an electricity market

Price elasticity matrix of demand in power system considering demand response programs

NASA Astrophysics Data System (ADS)

Qu, Xinyao; Hui, Hongxun; Yang, Shengchun; Li, Yaping; Ding, Yi

2018-02-01

The increasing renewable energy power generations have brought more intermittency and volatility to the electric power system. Demand-side resources can improve the consumption of renewable energy by demand response (DR), which becomes one of the important means to improve the reliability of power system. In price-based DR, the sensitivity analysis of customer’s power demand to the changing electricity prices is pivotal for setting reasonable prices and forecasting loads of power system. This paper studies the price elasticity matrix of demand (PEMD). An improved PEMD model is proposed based on elasticity effect weight, which can unify the rigid loads and flexible loads. Moreover, the structure of PEMD, which is decided by price policies and load types, and the calculation method of PEMD are also proposed. Several cases are studied to prove the effectiveness of this method.

Field Testing and Modeling of Supermarket Refrigeration Systems as a Demand Response Resource

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

Deru, Michael; Hirsch, Adam; Clark, Jordan

Supermarkets offer a substantial demand response (DR) resource because of their high energy intensity and use patterns; however, refrigeration as the largest load has been challenging to access. Previous work has analyzed supermarket DR using heating, ventilating, and air conditioning; lighting; and anti-sweat heaters. This project evaluated and quantified the DR potential inherent in supermarket refrigeration systems in the Bonneville Power Administration service territory. DR events were carried out and results measured in an operational 45,590-ft2 supermarket located in Hillsboro, Oregon. Key results from the project include the rate of temperature increase in freezer reach-in cases and walk-ins when refrigerationmore » is suspended, the load shed amount for DR tests, and the development of calibrated models to quantify available DR resources. Simulations showed that demand savings of 15 to 20 kilowatts (kW) are available for 1.5 hours for a typical store without precooling and for about 2.5 hours with precooling using only the low-temperature, non-ice cream cases. This represents an aggregated potential of 20 megawatts within BPA's service territory. Inability to shed loads for medium-temperature (MT) products because of the tighter temperature requirements is a significant barrier to realizing larger DR for supermarkets. Store owners are reluctant to allow MT case set point changes, and laboratory tests of MT case DR strategies are needed so that owners become comfortable testing, and implementing, MT case DR. The next-largest barrier is the lack of proper controls in most supermarket displays over ancillary equipment, such as anti-sweat heaters, lights, and fans.« less

A Generalized Formulation of Demand Response under Market Environments

NASA Astrophysics Data System (ADS)

Nguyen, Minh Y.; Nguyen, Duc M.

2015-06-01

This paper presents a generalized formulation of Demand Response (DR) under deregulated electricity markets. The problem is scheduling and controls the consumption of electrical loads according to the market price to minimize the energy cost over a day. Taking into account the modeling of customers' comfort (i.e., preference), the formulation can be applied to various types of loads including what was traditionally classified as critical loads (e.g., air conditioning, lights). The proposed DR scheme is based on Dynamic Programming (DP) framework and solved by DP backward algorithm in which the stochastic optimization is used to treat the uncertainty, if any occurred in the problem. The proposed formulation is examined with the DR problem of different loads, including Heat Ventilation and Air Conditioning (HVAC), Electric Vehicles (EVs) and a newly DR on the water supply systems of commercial buildings. The result of simulation shows significant saving can be achieved in comparison with their traditional (On/Off) scheme.

Auto-DR and Pre-cooling of Buildings at Tri-City Corporate Center

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

Yin, Rongxin; Xu, Peng; Kiliccote, Sila

2008-11-01

Over the several past years, Lawrence Berkeley National Laboratory (LBNL) has conducted field tests for different pre-cooling strategies in different commercial buildings within California. The test results indicated that pre-cooling strategies were effective in reducing electric demand in these buildings during peak periods. This project studied how to optimize pre-cooling strategies for eleven buildings in the Tri-City Corporate Center, San Bernardino, California with the assistance of a building energy simulation tool -- the Demand Response Quick Assessment Tool (DRQAT) developed by LBNL's Demand Response Research Center funded by the California Energy Commission's Public Interest Energy Research (PIER) Program. From themore » simulation results of these eleven buildings, optimal pre-cooling and temperature reset strategies were developed. The study shows that after refining and calibrating initial models with measured data, the accuracy of the models can be greatly improved and the models can be used to predict load reductions for automated demand response (Auto-DR) events. This study summarizes the optimization experience of the procedure to develop and calibrate building models in DRQAT. In order to confirm the actual effect of demand response strategies, the simulation results were compared to the field test data. The results indicated that the optimal demand response strategies worked well for all buildings in the Tri-City Corporate Center. This study also compares DRQAT with other building energy simulation tools (eQUEST and BEST). The comparison indicate that eQUEST and BEST underestimate the actual demand shed of the pre-cooling strategies due to a flaw in DOE2's simulation engine for treating wall thermal mass. DRQAT is a more accurate tool in predicting thermal mass effects of DR events.« less

Design and Cosimulation of Hierarchical Architecture for Demand Response Control and Coordination

DOE PAGES

Bhattarai, Bishnu P.; Levesque, Martin; Bak-Jensen, Birgitte; ...

2016-12-07

Demand response (DR) plays a key role for optimum asset utilization and to avoid or delay the need of new infrastructure investment. However, coordinated execution of multiple DRs is desired to maximize the DR benefits. In this paper, we propose a hierarchical DR architecture (HDRA) to control and coordinate the performance of various DR categories such that the operation of every DR category is backed-up by time delayed action of the others. A reliable, cost-effective communication infrastructure based on ZigBee, WiMAX, and fibers is designed to facilitate the HDRA execution. The performance of the proposed HDRA is demonstrated from themore » power system and communication perspectives in a cosimulation environment applied to a 0.4 kV/400 kVA real distribution network considering electric vehicles as a potential DR resource (DRR). The power simulation is performed employing a real time digital simulator whereas the communication simulation is performed using OMNeT++. Finally, the HDRA performance demonstrated the maximum utilization of available DR potential by facilitating simultaneous execution of multiple DRs and enabling participation of single DRR for multiple grid applications.« less

Design and Cosimulation of Hierarchical Architecture for Demand Response Control and Coordination

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

Bhattarai, Bishnu P.; Levesque, Martin; Bak-Jensen, Birgitte

Demand response (DR) plays a key role for optimum asset utilization and to avoid or delay the need of new infrastructure investment. However, coordinated execution of multiple DRs is desired to maximize the DR benefits. In this paper, we propose a hierarchical DR architecture (HDRA) to control and coordinate the performance of various DR categories such that the operation of every DR category is backed-up by time delayed action of the others. A reliable, cost-effective communication infrastructure based on ZigBee, WiMAX, and fibers is designed to facilitate the HDRA execution. The performance of the proposed HDRA is demonstrated from themore » power system and communication perspectives in a cosimulation environment applied to a 0.4 kV/400 kVA real distribution network considering electric vehicles as a potential DR resource (DRR). The power simulation is performed employing a real time digital simulator whereas the communication simulation is performed using OMNeT++. Finally, the HDRA performance demonstrated the maximum utilization of available DR potential by facilitating simultaneous execution of multiple DRs and enabling participation of single DRR for multiple grid applications.« less

Impacts of demand response and renewable generation in electricity power market

NASA Astrophysics Data System (ADS)

Zhao, Zhechong

This thesis presents the objective of the research which is to analyze the impacts of uncertain wind power and demand response on power systems operation and power market clearing. First, in order to effectively utilize available wind generation, it is usually given the highest priority by assigning zero or negative energy bidding prices when clearing the day-ahead electric power market. However, when congestion occurs, negative wind bidding prices would aggravate locational marginal prices (LMPs) to be negative in certain locations. A load shifting model is explored to alleviate possible congestions and enhance the utilization of wind generation, by shifting proper amount of load from peak hours to off peaks. The problem is to determine proper amount of load to be shifted, for enhancing the utilization of wind generation, alleviating transmission congestions, and making LMPs to be non-negative values. The second piece of work considered the price-based demand response (DR) program which is a mechanism for electricity consumers to dynamically manage their energy consumption in response to time-varying electricity prices. It encourages consumers to reduce their energy consumption when electricity prices are high, and thereby reduce the peak electricity demand and alleviate the pressure to power systems. However, it brings additional dynamics and new challenges on the real-time supply and demand balance. Specifically, price-sensitive DR load levels are constantly changing in response to dynamic real-time electricity prices, which will impact the economic dispatch (ED) schedule and in turn affect electricity market clearing prices. This thesis adopts two methods for examining the impacts of different DR price elasticity characteristics on the stability performance: a closed-loop iterative simulation method and a non-iterative method based on the contraction mapping theorem. This thesis also analyzes the financial stability of DR load consumers, by incorporating explicit LMP formulations and consumer payment requirements into the network-constrained unit commitment (NCUC) problem. The proposed model determines the proper amount of DR loads to be shifted from peak hours to off-peaks under ISO's direct load control, for reducing the operation cost and ensuring that consumer payments of DR loads will not deteriorate significantly after load shifting. Both MINLP and MILP models are discussed, and improved formulation strategies are presented.

Electric Water Heater Modeling and Control Strategies for Demand Response

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

Diao, Ruisheng; Lu, Shuai; Elizondo, Marcelo A.

2012-07-22

Abstract— Demand response (DR) has a great potential to provide balancing services at normal operating conditions and emergency support when a power system is subject to disturbances. Effective control strategies can significantly relieve the balancing burden of conventional generators and reduce investment on generation and transmission expansion. This paper is aimed at modeling electric water heaters (EWH) in households and tests their response to control strategies to implement DR. The open-loop response of EWH to a centralized signal is studied by adjusting temperature settings to provide regulation services; and two types of decentralized controllers are tested to provide frequency supportmore » following generator trips. EWH models are included in a simulation platform in DIgSILENT to perform electromechanical simulation, which contains 147 households in a distribution feeder. Simulation results show the dependence of EWH response on water heater usage . These results provide insight suggestions on the need of control strategies to achieve better performance for demand response implementation. Index Terms— Centralized control, decentralized control, demand response, electrical water heater, smart grid« less

Automated Dynamic Demand Response Implementation on a Micro-grid

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

Kuppannagari, Sanmukh R.; Kannan, Rajgopal; Chelmis, Charalampos

In this paper, we describe a system for real-time automated Dynamic and Sustainable Demand Response with sparse data consumption prediction implemented on the University of Southern California campus microgrid. Supply side approaches to resolving energy supply-load imbalance do not work at high levels of renewable energy penetration. Dynamic Demand Response (D 2R) is a widely used demand-side technique to dynamically adjust electricity consumption during peak load periods. Our D 2R system consists of accurate machine learning based energy consumption forecasting models that work with sparse data coupled with fast and sustainable load curtailment optimization algorithms that provide the ability tomore » dynamically adapt to changing supply-load imbalances in near real-time. Our Sustainable DR (SDR) algorithms attempt to distribute customer curtailment evenly across sub-intervals during a DR event and avoid expensive demand peaks during a few sub-intervals. It also ensures that each customer is penalized fairly in order to achieve the targeted curtailment. We develop near linear-time constant-factor approximation algorithms along with Polynomial Time Approximation Schemes (PTAS) for SDR curtailment that minimizes the curtailment error defined as the difference between the target and achieved curtailment values. Our SDR curtailment problem is formulated as an Integer Linear Program that optimally matches customers to curtailment strategies during a DR event while also explicitly accounting for customer strategy switching overhead as a constraint. We demonstrate the results of our D 2R system using real data from experiments performed on the USC smartgrid and show that 1) our prediction algorithms can very accurately predict energy consumption even with noisy or missing data and 2) our curtailment algorithms deliver DR with extremely low curtailment errors in the 0.01-0.05 kWh range.« less

BEopt-CA (Ex): A Tool for Optimal Integration of EE, DR and PV in Existing California Homes

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

Christensen, Craig; Horowitz, Scott; Maguire, Jeff

2014-04-01

This project targeted the development of a software tool, BEopt-CA (Ex) (Building Energy Optimization Tool for California Existing Homes), that aims to facilitate balanced integration of energy efficiency (EE), demand response (DR), and photovoltaics (PV) in the residential retrofit1 market. The intent is to provide utility program managers and contractors in the EE/DR/PV marketplace with a means of balancing the integration of EE, DR, and PV

Enabling Automated Dynamic Demand Response: From Theory to Practice

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

Frincu, Marc; Chelmis, Charalampos; Aman, Saima

2015-07-14

Demand response (DR) is a technique used in smart grids to shape customer load during peak hours. Automated DR offers utilities a fine grained control and a high degree of confidence in the outcome. However the impact on the customer's comfort means this technique is more suited for industrial and commercial settings than for residential homes. In this paper we propose a system for achieving automated controlled DR in a heterogeneous environment. We present some of the main issues arising in building such a system, including privacy, customer satisfiability, reliability, and fast decision turnaround, with emphasis on the solutions wemore » proposed. Based on the lessons we learned from empirical results we describe an integrated automated system for controlled DR on the USC microgrid. Results show that while on a per building per event basis the accuracy of our prediction and customer selection techniques varies, it performs well on average when considering several events and buildings.« less

Important Factors for Early Market Microgrids: Demand Response and Plug-in Electric Vehicle Charging

NASA Astrophysics Data System (ADS)

White, David Masaki

Microgrids are evolving concepts that are growing in interest due to their potential reliability, economic and environmental benefits. As with any new concept, there are many unresolved issues with regards to planning and operation. In particular, demand response (DR) and plug-in electric vehicle (PEV) charging are viewed as two key components of the future grid and both will likely be active technologies in the microgrid market. However, a better understanding of the economics associated with DR, the impact DR can have on the sizing of distributed energy resource (DER) systems and how to accommodate and price PEV charging is necessary to advance microgrid technologies. This work characterizes building based DR for a model microgrid, calculates the DER systems for a model microgrid under DR through a minimization of total cost, and determines pricing methods for a PEV charging station integrated with an individual building on the model microgrid. It is shown that DR systems which consist only of HVAC fan reductions provide potential economic benefits to the microgrid through participation in utility DR programs. Additionally, peak shaving DR reduces the size of power generators, however increasing DR capacity does not necessarily lead to further reductions in size. As it currently stands for a microgrid that is an early adopter of PEV charging, current installation costs of PEV charging equipment lead to a system that is not competitive with established commercial charging networks or to gasoline prices for plug-in hybrid electric vehicles (PHEV).

Future Opportunities and Challenges with Using Demand Response as a Resource in Distribution System Operation and Planning Activities

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

Cappers, Peter; MacDonald, Jason; Page, Janie

2016-01-01

This scoping study focuses on identifying the ability for current and future demand response opportunities to contribute to distribution system management. To do so, this scoping study will identify the needs of a distribution system to operate efficiently, safely and reliably; summarize both benefits and challenges for the operation of the distribution system with high penetration levels of distributed energy resources; define a suite of services based on those changing operational needs that could be provided by resources; identify existing demand response opportunities sponsored by distribution utilities and/or aggregators of retail customers; assess the extent to which distribution system servicesmore » can be provided via DR opportunities both in their current form and with alterations to their design; and provide a qualitative assessment of coordination issues that bulk power and distribution system providers of DR opportunities will need to address.« less

An ILP based Algorithm for Optimal Customer Selection for Demand Response in SmartGrids

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

Kuppannagari, Sanmukh R.; Kannan, Rajgopal; Prasanna, Viktor K.

Demand Response (DR) events are initiated by utilities during peak demand periods to curtail consumption. They ensure system reliability and minimize the utility’s expenditure. Selection of the right customers and strategies is critical for a DR event. An effective DR scheduling algorithm minimizes the curtailment error which is the absolute difference between the achieved curtailment value and the target. State-of-the-art heuristics exist for customer selection, however their curtailment errors are unbounded and can be as high as 70%. In this work, we develop an Integer Linear Programming (ILP) formulation for optimally selecting customers and curtailment strategies that minimize the curtailmentmore » error during DR events in SmartGrids. We perform experiments on real world data obtained from the University of Southern California’s SmartGrid and show that our algorithm achieves near exact curtailment values with errors in the range of 10 -7 to 10 -5, which are within the range of numerical errors. We compare our results against the state-of-the-art heuristic being deployed in practice in the USC SmartGrid. We show that for the same set of available customer strategy pairs our algorithm performs 103 to 107 times better in terms of the curtailment errors incurred.« less

Increased Coal Plant Flexibility Can Improve Renewables Integration |

Science.gov Websites

practices that enable lower turndowns, faster starts and stops, and faster ramping between load set-points faster ramp rates and faster and less expensive starts. Flexible Load - Demand Response Resources Demand response (DR) is a load management practice of deliberately reducing or adding load to balance the system

2025 California Demand Response Potential Study - Charting California’s Demand Response Future. Final Report on Phase 2 Results

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

Alstone, Peter; Potter, Jennifer; Piette, Mary Ann

California’s legislative and regulatory goals for renewable energy are changing the power grid’s dynamics. Increased variable generation resource penetration connected to the bulk power system, as well as, distributed energy resources (DERs) connected to the distribution system affect the grid’s reliable operation over many different time scales (e.g., days to hours to minutes to seconds). As the state continues this transition, it will require careful planning to ensure resources with the right characteristics are available to meet changing grid management needs. Demand response (DR) has the potential to provide important resources for keeping the electricity grid stable and efficient, tomore » defer upgrades to generation, transmission and distribution systems, and to deliver customer economic benefits. This study estimates the potential size and cost of future DR resources for California’s three investor-owned utilities (IOUs): Pacific Gas and Electric Company (PG&E), Southern California Edison Company (SCE), and San Diego Gas & Electric Company (SDG&E). Our goal is to provide data-driven insights as the California Public Utilities Commission (CPUC) evaluates how to enhance DR’s role in meeting California’s resource planning needs and operational requirements. We address two fundamental questions: 1. What cost-competitive DR service types will meet California’s future grid needs as it moves towards clean energy and advanced infrastructure? 2. What is the size and cost of the expected resource base for the DR service types?« less

Modeling, Analysis, and Control of Demand Response Resources

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

Mathieu, Johanna L.

2012-05-01

While the traditional goal of an electric power system has been to control supply to fulfill demand, the demand-side can plan an active role in power systems via Demand Response (DR), defined by the Department of Energy (DOE) as “a tariff or program established to motivate changes in electric use by end-use customers in response to changes in the price of electricity over time, or to give incentive payments designed to induce lower electricity use at times of high market prices or when grid reliability is jeopardized” [29]. DR can provide a variety of benefits including reducing peak electric loadsmore » when the power system is stressed and fast timescale energy balancing. Therefore, DR can improve grid reliability and reduce wholesale energy prices and their volatility. This dissertation focuses on analyzing both recent and emerging DR paradigms. Recent DR programs have focused on peak load reduction in commercial buildings and industrial facilities (C&I facilities). We present methods for using 15-minute-interval electric load data, commonly available from C&I facilities, to help building managers understand building energy consumption and ‘ask the right questions’ to discover opportunities for DR. Additionally, we present a regression-based model of whole building electric load, i.e., a baseline model, which allows us to quantify DR performance. We use this baseline model to understand the performance of 38 C&I facilities participating in an automated dynamic pricing DR program in California. In this program, facilities are expected to exhibit the same response each DR event. We find that baseline model error makes it difficult to precisely quantify changes in electricity consumption and understand if C&I facilities exhibit event-to-event variability in their response to DR signals. Therefore, we present a method to compute baseline model error and a metric to determine how much observed DR variability results from baseline model error rather than real variability in response. We find that, in general, baseline model error is large. Though some facilities exhibit real DR variability, most observed variability results from baseline model error. In some cases, however, aggregations of C&I facilities exhibit real DR variability, which could create challenges for power system operation. These results have implications for DR program design and deployment. Emerging DR paradigms focus on faster timescale DR. Here, we investigate methods to coordinate aggregations of residential thermostatically controlled loads (TCLs), including air conditioners and refrigerators, to manage frequency and energy imbalances in power systems. We focus on opportunities to centrally control loads with high accuracy but low requirements for sensing and communications infrastructure. Specifically, we compare cases when measured load state information (e.g., power consumption and temperature) is 1) available in real time; 2) available, but not in real time; and 3) not available. We develop Markov Chain models to describe the temperature state evolution of heterogeneous populations of TCLs, and use Kalman filtering for both state and joint parameter/state estimation. We present a look-ahead proportional controller to broadcast control signals to all TCLs, which always remain in their temperature dead-band. Simulations indicate that it is possible to achieve power tracking RMS errors in the range of 0.26–9.3% of steady state aggregated power consumption. Results depend upon the information available for system identification, state estimation, and control. We find that, depending upon the performance required, TCLs may not need to provide state information to the central controller in real time or at all. We also estimate the size of the TCL potential resource; potential revenue from participation in markets; and break-even costs associated with deploying DR-enabling technologies. We find that current TCL energy storage capacity in California is 8–11 GWh, with refrigerators contributing the most. Annual revenues from participation in regulation vary from $10 to $220 per TCL per year depending upon the type of TCL and climate zone, while load following and arbitrage revenues are more modest at $2 to $35 per TCL per year. These results lead to a number of policy recommendations that will make it easier to engage residential loads in fast timescale DR.« less

User-Preference-Driven Model Predictive Control of Residential Building Loads and Battery Storage for Demand Response: Preprint

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

Jin, Xin; Baker, Kyri A.; Christensen, Dane T.

This paper presents a user-preference-driven home energy management system (HEMS) for demand response (DR) with residential building loads and battery storage. The HEMS is based on a multi-objective model predictive control algorithm, where the objectives include energy cost, thermal comfort, and carbon emission. A multi-criterion decision making method originating from social science is used to quickly determine user preferences based on a brief survey and derive the weights of different objectives used in the optimization process. Besides the residential appliances used in the traditional DR programs, a home battery system is integrated into the HEMS to improve the flexibility andmore » reliability of the DR resources. Simulation studies have been performed on field data from a residential building stock data set. Appliance models and usage patterns were learned from the data to predict the DR resource availability. Results indicate the HEMS was able to provide a significant amount of load reduction with less than 20% prediction error in both heating and cooling cases.« less

User-Preference-Driven Model Predictive Control of Residential Building Loads and Battery Storage for Demand Response

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

Jin, Xin; Baker, Kyri A; Isley, Steven C

This paper presents a user-preference-driven home energy management system (HEMS) for demand response (DR) with residential building loads and battery storage. The HEMS is based on a multi-objective model predictive control algorithm, where the objectives include energy cost, thermal comfort, and carbon emission. A multi-criterion decision making method originating from social science is used to quickly determine user preferences based on a brief survey and derive the weights of different objectives used in the optimization process. Besides the residential appliances used in the traditional DR programs, a home battery system is integrated into the HEMS to improve the flexibility andmore » reliability of the DR resources. Simulation studies have been performed on field data from a residential building stock data set. Appliance models and usage patterns were learned from the data to predict the DR resource availability. Results indicate the HEMS was able to provide a significant amount of load reduction with less than 20% prediction error in both heating and cooling cases.« less

DReAM: Demand Response Architecture for Multi-level District Heating and Cooling Networks

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

Bhattacharya, Saptarshi; Chandan, Vikas; Arya, Vijay

In this paper, we exploit the inherent hierarchy of heat exchangers in District Heating and Cooling (DHC) networks and propose DReAM, a novel Demand Response (DR) architecture for Multi-level DHC networks. DReAM serves to economize system operation while still respecting comfort requirements of individual consumers. Contrary to many present day DR schemes that work on a consumer level granularity, DReAM works at a level of hierarchy above buildings, i.e. substations that supply heat to a group of buildings. This improves the overall DR scalability and reduce the computational complexity. In the first step of the proposed approach, mathematical models ofmore » individual substations and their downstream networks are abstracted into appropriately constructed low-complexity structural forms. In the second step, this abstracted information is employed by the utility to perform DR optimization that determines the optimal heat inflow to individual substations rather than buildings, in order to achieve the targeted objectives across the network. We validate the proposed DReAM framework through experimental results under different scenarios on a test network.« less

Automated Demand Response for Energy Sustainability Cost and Performance Report

DTIC Science & Technology

2015-09-01

Install solar thermal system for pool heating in fitness Bldg 325 2022 $ 21,359 $ 7,199 3.6 yrs Renewable energy project p. 124- 126 Note: All data...and R. Bienert, 2011. Smart Grid Standards and Systems Interoperability: A Precedent with OpenADR, Lawrence Berkeley National Laboratory, LBNL...response (DR) system at Fort Irwin, CA. This demonstration employed industry-standard OpenADR (Open Automated Demand Response) technology to perform

Co-optimization of Energy and Demand-Side Reserves in Day-Ahead Electricity Markets

NASA Astrophysics Data System (ADS)

Surender Reddy, S.; Abhyankar, A. R.; Bijwe, P. R.

2015-04-01

This paper presents a new multi-objective day-ahead market clearing (DAMC) mechanism with demand-side reserves/demand response (DR) offers, considering realistic voltage-dependent load modeling. The paper proposes objectives such as social welfare maximization (SWM) including demand-side reserves, and load served error (LSE) minimization. In this paper, energy and demand-side reserves are cleared simultaneously through co-optimization process. The paper clearly brings out the unsuitability of conventional SWM for DAMC in the presence of voltage-dependent loads, due to reduction of load served (LS). Under such circumstances multi-objective DAMC with DR offers is essential. Multi-objective Strength Pareto Evolutionary Algorithm 2+ (SPEA 2+) has been used to solve the optimization problem. The effectiveness of the proposed scheme is confirmed with results obtained from IEEE 30 bus system.

Electricity demand and storage dispatch modeling for buildings and implications for the smartgrid

NASA Astrophysics Data System (ADS)

Zheng, Menglian; Meinrenken, Christoph

2013-04-01

As an enabler for demand response (DR), electricity storage in buildings has the potential to lower costs and carbon footprint of grid electricity while simultaneously mitigating grid strain and increasing its flexibility to integrate renewables (central or distributed). We present a stochastic model to simulate minute-by-minute electricity demand of buildings and analyze the resulting electricity costs under actual, currently available DR-enabling tariffs in New York State, namely a peak/offpeak tariff charging by consumed energy (monthly total kWh) and a time of use tariff charging by power demand (monthly peak kW). We then introduce a variety of electrical storage options (from flow batteries to flywheels) and determine how DR via temporary storage may increase the overall net present value (NPV) for consumers (comparing the reduced cost of electricity to capital and maintenance costs of the storage). We find that, under the total-energy tariff, only medium-term storage options such as batteries offer positive NPV, and only at the low end of storage costs (optimistic scenario). Under the peak-demand tariff, however, even short-term storage such as flywheels and superconducting magnetic energy offer positive NPV. Therefore, these offer significant economic incentive to enable DR without affecting the consumption habits of buildings' residents. We discuss implications for smartgrid communication and our future work on real-time price tariffs.

Costs to Automate Demand Response - Taxonomy and Results from Field Studies and Programs

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

Piette, Mary A.; Schetrit, Oren; Kiliccote, Sila

During the past decade, the technology to automate demand response (DR) in buildings and industrial facilities has advanced significantly. Automation allows rapid, repeatable, reliable operation. This study focuses on costs for DR automation in commercial buildings with some discussion on residential buildings and industrial facilities. DR automation technology relies on numerous components, including communication systems, hardware and software gateways, standards-based messaging protocols, controls and integration platforms, and measurement and telemetry systems. This report compares cost data from several DR automation programs and pilot projects, evaluates trends in the cost per unit of DR and kilowatts (kW) available from automated systems,more » and applies a standard naming convention and classification or taxonomy for system elements. Median costs for the 56 installed automated DR systems studied here are about $200/kW. The deviation around this median is large with costs in some cases being an order of magnitude great or less than the median. This wide range is a result of variations in system age, size of load reduction, sophistication, and type of equipment included in cost analysis. The costs to automate fast DR systems for ancillary services are not fully analyzed in this report because additional research is needed to determine the total cost to install, operate, and maintain these systems. However, recent research suggests that they could be developed at costs similar to those of existing hot-summer DR automation systems. This report considers installation and configuration costs and does include the costs of owning and operating DR automation systems. Future analysis of the latter costs should include the costs to the building or facility manager costs as well as utility or third party program manager cost.« less

Turnkey Heating, Ventilating, and Air Conditioning and Lighting Retrofit Solution Combining Energy Efficiency and Demand Response Benefits

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

Doebber, Ian; Deru, Michael; Trenbath, Kim

NREL worked with the Bonneville Power Administration's Technology Innovation Office to demonstrate a turnkey, retrofit technology that combines demand response (DR) and energy efficiency (EE) benefits for HVAC and lighting in retail buildings. As a secondary benefit, we also controlled various plug loads and electric hot water heaters (EHWH). The technology demonstrated was Transformative Wave's eIQ Building Management System (BMS) automatically responding to DR signals. The BMS controlled the HVAC rooftop units (RTU) using the CATALYST retrofit solution also developed by Transformative Wave. The non-HVAC loads were controlled using both hardwired and ZigBee wireless communication. The wireless controllers, manufactured bymore » Autani, were used when the building's electrical layout was too disorganized to leverage less expensive hardwired control. The six demonstration locations are within the Seattle metro area. Based on the assets curtailed by the BMS at each location, we projected the DR resource. We were targeting a 1.7 W/ft2 shed for the summer Day-Ahead events and a 0.7 W/ft2 shed for the winter events. While summarized in Table ES-1, only one summer DR event was conducted at Casino #2.« less

Field Testing of Telemetry for Demand Response Control of Small Loads

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

Lanzisera, Steven; Weber, Adam; Liao, Anna

The electricity system in California, from generation through loads, must be prepared for high renewable penetration and increased electrification of end uses while providing increased resilience and lower operating cost. California has an aggressive renewable portfolio standard that is complemented by world-leading greenhouse gas goals. The goal of this project was to evaluate methods of enabling fast demand response (DR) signaling to small loads for low-cost site enablement. We used OpenADR 2.0 to meet telemetry requirements for providing ancillary services, and we used a variety of low-cost devices coupled with open-source software to enable an end-to-end fast DR. The devices,more » architecture, implementation, and testing of the system is discussed in this report. We demonstrate that the emerging Internet of Things (IoT) and Smart Home movements provide an opportunity for diverse small loads to provide fast, low-cost demand response. We used Internet-connected lights, thermostats, load interruption devices, and water heaters to demonstrate an ecosystem of controllable devices. The system demonstrated is capable of providing fast load shed for between 20 dollars and $300 per kilowatt (kW) of available load. The wide range results from some loads may have very low cost but also very little shed capability (a 10 watt [W] LED light can only shed a maximum of 10 W) while some loads (e.g., water heaters or air conditioners) can shed several kilowatts but have a higher initial cost. These costs, however, compare well with other fast demand response costs, with typically are over $100/kilowatt of shed. We contend these loads are even more attractive than their price suggests because many of them will be installed for energy efficiency or non-energy benefits (e.g., improved lighting quality or controllability), and the ability to use them for fast DR is a secondary benefit. Therefore the cost of enabling them for DR may approach zero if a software-only solution can be deployed to enable fast DR after devices are installed for other reasons. We recommend that the DR research community continue to engage with the IoT community to encourage the use of documented and open development interfaces. A library of device drivers and machine-readable interface specifications would significantly reduce the burden on users or system integrators for deploying systems in large numbers of buildings in California.« less

To Boldly Go: America's Next Era in Space. Sustaining Life on the Earth

NASA Technical Reports Server (NTRS)

2004-01-01

Dr. France Cordova, NASA's Chief Scientist, opened this, the sixth seminar in the Administrator's Seminar Series, by introducing NASA Administrator Daniel S. Goldin. Mr Goldin welcomed the attendees and set the stage for Dr. Cordova's introduction of the first speaker, Dr. Robert Kates of Brown University. Dr. Kates primary concerns are global environmental changes, world hunger, and the size of the population. Human changes, he said, rival the changes of nature. Changes in the size of world population affect the need for more agricultural products, therefore more land for growing food, which leads to deforestation, which affects rainfall, and therefore the water supply which is in increased demand. Human ingenuity can reduce some shortages but generally doesn't keep up with increased demand for life-sustaining essentials. These problems require the concern of intergovernmental organizations, treaties and activities, as well as transnational corporations, and non-governmental and private, volunteer organizations. Next Dr. Diana Liverman of Pennsylvania State University spoke on human interactions regarding climate and society. She considered the effect of changes in land use on climate, using Mexico as an example. Mexicans changed from raising much wheat to raising more fruits and vegetables. This was in response to the demands of the market. The results were more industry, population growth, greater income, drought (because the new crops required more water), and conflicts over water supplies. Dr. Charles Kennel of the Office of Mission to Planet Earth joined Dr.s Cordova, Kates, and Liverman for the question and answer session that followed.

A Hybrid Demand Response Simulator Version 1.0

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

2012-05-02

A hybrid demand response simulator is developed to test different control algorithms for centralized and distributed demand response (DR) programs in a small distribution power grid. The HDRS is designed to model a wide variety of DR services such as peak having, load shifting, arbitrage, spinning reserves, load following, regulation, emergency load shedding, etc. The HDRS does not model the dynamic behaviors of the loads, rather, it simulates the load scheduling and dispatch process. The load models include TCAs (water heaters, air conditioners, refrigerators, freezers, etc) and non-TCAs (lighting, washer, dishwasher, etc.) The ambient temperature changes, thermal resistance, capacitance, andmore » the unit control logics can be modeled for TCA loads. The use patterns of the non-TCA can be modeled by probability of use and probabilistic durations. Some of the communication network characteristics, such as delays and errors, can also be modeled. Most importantly, because the simulator is modular and greatly simplified the thermal models for TCA loads, it is very easy and fast to be used to test and validate different control algorithms in a simulated environment.« less

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

Hummon, M.; Kiliccote, S.

Demand response (DR) resources present a potentially important source of grid flexibility however, DR in grid models is limited by data availability and modeling complexity. This presentation focuses on the co-optimization of DR resources to provide energy and ancillary services in a production cost model of the Colorado "test system". We assume each DR resource can provide energy services by either shedding load or shifting its use between different times, as well as operating reserves: frequency regulation, contingency reserve, and flexibility (or ramping) reserve. There are significant variations in the availabilities of different types of DR resources, which affect bothmore » the operational savings as well as the revenue for each DR resource. The results presented include the system-wide avoided fuel and generator start-up costs as well as the composite revenue for each DR resource by energy and operating reserves.« less

Learning to REDUCE: A Reduced Electricity Consumption Prediction Ensemble

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

Aman, Saima; Chelmis, Charalampos; Prasanna, Viktor

Utilities use Demand Response (DR) to balance supply and demand in the electric grid by involving customers in efforts to reduce electricity consumption during peak periods. To implement and adapt DR under dynamically changing conditions of the grid, reliable prediction of reduced consumption is critical. However, despite the wealth of research on electricity consumption prediction and DR being long in practice, the problem of reduced consumption prediction remains largely un-addressed. In this paper, we identify unique computational challenges associated with the prediction of reduced consumption and contrast this to that of normal consumption and DR baseline prediction.We propose a novelmore » ensemble model that leverages different sequences of daily electricity consumption on DR event days as well as contextual attributes for reduced consumption prediction. We demonstrate the success of our model on a large, real-world, high resolution dataset from a university microgrid comprising of over 950 DR events across a diverse set of 32 buildings. Our model achieves an average error of 13.5%, an 8.8% improvement over the baseline. Our work is particularly relevant for buildings where electricity consumption is not tied to strict schedules. Our results and insights should prove useful to the researchers and practitioners working in the sustainable energy domain.« less

Research on Simulation Requirements and Business Architecture of Automated Demand Response in Power Sales Side Market Liberalization

NASA Astrophysics Data System (ADS)

Liu, Yiqun; Zhou, Pengcheng; Zeng, Ming; Chen, Songsong

2018-01-01

With the gradual reform of the electricity market, the power sale side liberalization has become the focus of attention as the key task of reform. The open power market provides a good environment for DR (Demand Response). It is of great significance to research the simulation requirements and business architecture of ADR (Automatic Demand Response) in power sale side market liberalization. Firstly, this paper analyzes the simulation requirements of ADR. Secondly, it analyzes the influence factors that the business development of ADR from five aspects after power sale side market liberalization. Finally, Based on ADR technology support system, the business architecture of ADR after power sale side market liberalization is constructed.

Microgrid to enable optimal distributed energy retail and end-user demand response

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

Jin, Ming; Feng, Wei; Marnay, Chris

In the face of unprecedented challenges in environmental sustainability and grid resilience, there is an increasingly held consensus regarding the adoption of distributed and renewable energy resources such as microgrids (MGs), and the utilization of flexible electric loads by demand response (DR) to potentially drive a necessary paradigm shift in energy production and consumption patterns. However, the potential value of distributed generation and demand flexibility has not yet been fully realized in the operation of MGs. This study investigates the pricing and operation strategy with DR for a MG retailer in an integrated energy system (IES). Based on co-optimizing retailmore » rates and MG dispatch formulated as a mixed integer quadratic programming (MIQP) problem, our model devises a dynamic pricing scheme that reflects the cost of generation and promotes DR, in tandem with an optimal dispatch plan that exploits spark spread and facilitates the integration of renewables, resulting in improved retailer profits and system stability. Main issues like integrated energy coupling and customer bill reduction are addressed during pricing to ensure rates competitiveness and customer protection. By evaluating on real datasets, the system is demonstrated to optimally coordinate storage, renewables, and combined heat and power (CHP), reduce carbon dioxide emission while maintaining profits, and effectively alleviate the PV curtailment problem. Finally, the model can be used by retailers and MG operators to optimize their operations, as well as regulators to design new utility rates in support of the ongoing transformation of energy systems.« less

Microgrid to enable optimal distributed energy retail and end-user demand response

DOE PAGES

Jin, Ming; Feng, Wei; Marnay, Chris; ...

2018-06-07

In the face of unprecedented challenges in environmental sustainability and grid resilience, there is an increasingly held consensus regarding the adoption of distributed and renewable energy resources such as microgrids (MGs), and the utilization of flexible electric loads by demand response (DR) to potentially drive a necessary paradigm shift in energy production and consumption patterns. However, the potential value of distributed generation and demand flexibility has not yet been fully realized in the operation of MGs. This study investigates the pricing and operation strategy with DR for a MG retailer in an integrated energy system (IES). Based on co-optimizing retailmore » rates and MG dispatch formulated as a mixed integer quadratic programming (MIQP) problem, our model devises a dynamic pricing scheme that reflects the cost of generation and promotes DR, in tandem with an optimal dispatch plan that exploits spark spread and facilitates the integration of renewables, resulting in improved retailer profits and system stability. Main issues like integrated energy coupling and customer bill reduction are addressed during pricing to ensure rates competitiveness and customer protection. By evaluating on real datasets, the system is demonstrated to optimally coordinate storage, renewables, and combined heat and power (CHP), reduce carbon dioxide emission while maintaining profits, and effectively alleviate the PV curtailment problem. Finally, the model can be used by retailers and MG operators to optimize their operations, as well as regulators to design new utility rates in support of the ongoing transformation of energy systems.« less

Residential Consumer-Centric Demand-Side Management Based on Energy Disaggregation-Piloting Constrained Swarm Intelligence: Towards Edge Computing

PubMed Central

Hu, Yu-Chen

2018-01-01

The emergence of smart Internet of Things (IoT) devices has highly favored the realization of smart homes in a down-stream sector of a smart grid. The underlying objective of Demand Response (DR) schemes is to actively engage customers to modify their energy consumption on domestic appliances in response to pricing signals. Domestic appliance scheduling is widely accepted as an effective mechanism to manage domestic energy consumption intelligently. Besides, to residential customers for DR implementation, maintaining a balance between energy consumption cost and users’ comfort satisfaction is a challenge. Hence, in this paper, a constrained Particle Swarm Optimization (PSO)-based residential consumer-centric load-scheduling method is proposed. The method can be further featured with edge computing. In contrast with cloud computing, edge computing—a method of optimizing cloud computing technologies by driving computing capabilities at the IoT edge of the Internet as one of the emerging trends in engineering technology—addresses bandwidth-intensive contents and latency-sensitive applications required among sensors and central data centers through data analytics at or near the source of data. A non-intrusive load-monitoring technique proposed previously is utilized to automatic determination of physical characteristics of power-intensive home appliances from users’ life patterns. The swarm intelligence, constrained PSO, is used to minimize the energy consumption cost while considering users’ comfort satisfaction for DR implementation. The residential consumer-centric load-scheduling method proposed in this paper is evaluated under real-time pricing with inclining block rates and is demonstrated in a case study. The experimentation reported in this paper shows the proposed residential consumer-centric load-scheduling method can re-shape loads by home appliances in response to DR signals. Moreover, a phenomenal reduction in peak power consumption is achieved by 13.97%. PMID:29702607

Response to the Directorate of Health Care Studies and Clinical Investigations Final Report (Revised) Assessing Power Analysis Approaches for the Fort Bragg Evaluation Project

DTIC Science & Technology

1993-07-28

Below is a summary of Vanderbilt’s response, requested by Health Services Command ( HSC ), to the final report prepared by the Directorate of Health Care...Command’s ( HSC ) demands for client data it sought to use somehow in power analysis (see Appendix F). Dr. Kapadia’s statement is the standard view held...not involve actual data, the results from this method may be entirely misleading and not accurate." When HSC demanded client data for power analysis in

Laboratory Testing of Demand-Response Enabled Household Appliances

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

Sparn, B.; Jin, X.; Earle, L.

2013-10-01

With the advent of the Advanced Metering Infrastructure (AMI) systems capable of two-way communications between the utility's grid and the building, there has been significant effort in the Automated Home Energy Management (AHEM) industry to develop capabilities that allow residential building systems to respond to utility demand events by temporarily reducing their electricity usage. Major appliance manufacturers are following suit by developing Home Area Network (HAN)-tied appliance suites that can take signals from the home's 'smart meter,' a.k.a. AMI meter, and adjust their run cycles accordingly. There are numerous strategies that can be employed by household appliances to respond tomore » demand-side management opportunities, and they could result in substantial reductions in electricity bills for the residents depending on the pricing structures used by the utilities to incent these types of responses.The first step to quantifying these end effects is to test these systems and their responses in simulated demand-response (DR) conditions while monitoring energy use and overall system performance.« less

Laboratory Testing of Demand-Response Enabled Household Appliances

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

Sparn, B.; Jin, X.; Earle, L.

2013-10-01

With the advent of the Advanced Metering Infrastructure (AMI) systems capable of two-way communications between the utility's grid and the building, there has been significant effort in the Automated Home Energy Management (AHEM) industry to develop capabilities that allow residential building systems to respond to utility demand events by temporarily reducing their electricity usage. Major appliance manufacturers are following suit by developing Home Area Network (HAN)-tied appliance suites that can take signals from the home's 'smart meter,' a.k.a. AMI meter, and adjust their run cycles accordingly. There are numerous strategies that can be employed by household appliances to respond tomore » demand-side management opportunities, and they could result in substantial reductions in electricity bills for the residents depending on the pricing structures used by the utilities to incent these types of responses. The first step to quantifying these end effects is to test these systems and their responses in simulated demand-response (DR) conditions while monitoring energy use and overall system performance.« less

Impacts of Demand-Side Resources on Electric Transmission Planning

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

Hadley, Stanton W.; Sanstad, Alan H.

2015-01-01

Will demand resources such as energy efficiency (EE), demand response (DR), and distributed generation (DG) have an impact on electricity transmission requirements? Five drivers for transmission expansion are discussed: interconnection, reliability, economics, replacement, and policy. With that background, we review the results of a set of transmission studies that were conducted between 2010 and 2013 by electricity regulators, industry representatives, and other stakeholders in the three physical interconnections within the United States. These broad-based studies were funded by the US Department of Energy and included scenarios of reduced load growth due to EE, DR, and DG. While the studies weremore » independent and used different modeling tools and interconnect-specific assumptions, all provided valuable results and insights. However, some caveats exist. Demand resources were evaluated in conjunction with other factors, and limitations on transmission additions between scenarios made understanding the role of demand resources difficult. One study, the western study, included analyses over both 10- and 20-year planning horizons; the 10-year analysis did not show near-term reductions in transmission, but the 20-year indicated fewer transmission additions, yielding a 36percent capital cost reduction. In the eastern study the reductions in demand largely led to reductions in local generation capacity and an increased opportunity for low-cost and renewable generation to export to other regions. The Texas study evaluated generation changes due to demand, and is in the process of examining demand resource impacts on transmission.« less

Comparison of Actual Costs to Integrate Commercial Buildings with the Grid

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

Piette, Mary Ann; Black, Doug; Yin, Rongxin

During the past decade, the technology to automate demand response (DR) in buildings and industrial facilities has advanced significantly. Automation allows rapid, repeatable, reliable operation. This study focuses on costs for DR automation in commercial buildings with some discussion on residential buildings and industrial facilities. DR automation technology relies on numerous components, including communication systems, hardware and software gateways, standards-based messaging protocols, controls and integration platforms, and measurement and telemetry systems. This paper discusses the impact factors that contribute to the costs of automated DR systems, with a focus on OpenADR 1.0 and 2.0 systems. In addition, this report comparesmore » cost data from several DR automation programs and pilot projects, evaluates trends in the cost per unit of DR and kilowatts (kW) available from automated systems, and applies a standard naming convention and classification or taxonomy for system elements. In summary, median costs for the 56 installed automated DR systems studied here are about $200/kW. The deviation around this median is large with costs in some cases being an order of magnitude greater or less than median. Costs to automate fast DR systems for ancillary services are not fully analyzed in this report because additional research is needed to determine the total such costs.« less

Residential Consumer-Centric Demand-Side Management Based on Energy Disaggregation-Piloting Constrained Swarm Intelligence: Towards Edge Computing.

PubMed

Lin, Yu-Hsiu; Hu, Yu-Chen

2018-04-27

The emergence of smart Internet of Things (IoT) devices has highly favored the realization of smart homes in a down-stream sector of a smart grid. The underlying objective of Demand Response (DR) schemes is to actively engage customers to modify their energy consumption on domestic appliances in response to pricing signals. Domestic appliance scheduling is widely accepted as an effective mechanism to manage domestic energy consumption intelligently. Besides, to residential customers for DR implementation, maintaining a balance between energy consumption cost and users’ comfort satisfaction is a challenge. Hence, in this paper, a constrained Particle Swarm Optimization (PSO)-based residential consumer-centric load-scheduling method is proposed. The method can be further featured with edge computing. In contrast with cloud computing, edge computing—a method of optimizing cloud computing technologies by driving computing capabilities at the IoT edge of the Internet as one of the emerging trends in engineering technology—addresses bandwidth-intensive contents and latency-sensitive applications required among sensors and central data centers through data analytics at or near the source of data. A non-intrusive load-monitoring technique proposed previously is utilized to automatic determination of physical characteristics of power-intensive home appliances from users’ life patterns. The swarm intelligence, constrained PSO, is used to minimize the energy consumption cost while considering users’ comfort satisfaction for DR implementation. The residential consumer-centric load-scheduling method proposed in this paper is evaluated under real-time pricing with inclining block rates and is demonstrated in a case study. The experimentation reported in this paper shows the proposed residential consumer-centric load-scheduling method can re-shape loads by home appliances in response to DR signals. Moreover, a phenomenal reduction in peak power consumption is achieved by 13.97%.

Smart Grid Development: Multinational Demo Project Analysis

NASA Astrophysics Data System (ADS)

Oleinikova, I.; Mutule, A.; Obushevs, A.; Antoskovs, N.

2016-12-01

This paper analyses demand side management (DSM) projects and stakeholders' experience with the aim to develop, promote and adapt smart grid tehnologies in Latvia. The research aims at identifying possible system service posibilites, including demand response (DR) and determining the appropriate market design for such type of services to be implemented at the Baltic power system level, with the cooperation of distribution system operator (DSO) and transmission system operator (TSO). This paper is prepared as an extract from the global smart grid best practices, smart solutions and business models.

The Demand Reduction Potential of Smart Appliances in U.S. Homes

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

Makhmalbaf, Atefe; Srivastava, Viraj; Parker, Graham B.

The widespread deployment of demand respond (DR) enabled home appliances is expected to have significant reduction in the demand of electricity during peak hours. The work documented in this paper focuses on estimating the energy shift resulting from the installation of DR enabled smart appliances in the U.S. This estimation is based on analyzing the market for smart appliances and calculating the total energy demand that can potentially be shifted by DR control in appliances. Appliance operation is examined by considering their sub components individually to identify their energy consumptions and savings resulting from interrupting and shifting their load, e.g.,more » by delaying the refrigerator defrost cycle. In addition to major residential appliances, residential pool pumps are also included in this study given their energy consumption profiles that make them favorable for DR applications. In the market analysis study documented in this paper, the U.S. Energy Information Administration's (EIA) Residential Energy Consumption Survey (RECS) and National Association of Home Builders (NAHB) databases are used to examine the expected life of an appliance, the number of appliances installed in homes constructed in 10 year intervals after 1940 and home owner income. Conclusions about the effectiveness of the smart appliances in reducing electrical demand have been drawn and a ranking of appliances in terms of their contribution to load shift is presented. E.g., it was concluded that DR enabled water heaters result in the maximum load shift; whereas, dishwashers have the highest user elasticity and hence the highest potential for load shifting through DR. This work is part of a larger effort to bring novel home energy management concepts and technologies to reduce energy consumption, reduce peak electricity demand, integrate renewables and storage technology, and change homeowner behavior to manage and consume less energy and potentially save consumer energy costs.« less

Essays on Mathematical Optimization for Residential Demand Response in the Energy Sector

NASA Astrophysics Data System (ADS)

Palaparambil Dinesh, Lakshmi

In the electric utility industry, it could be challenging to adjust supply to match demand due to large generator ramp up times, high generation costs and insufficient in-house generation capacity. Demand response (DR) is a technique for adjusting the demand for electric power instead of the supply. Direct Load Control (DLC) is one of the ways to implement DR. DLC program participants sign up for power interruption contracts and are given financial incentives for curtailing electricity usage during peak demand time periods. This dissertation studies a DLC program for residential air conditioners using mathematical optimization models. First, we develop a model that determines what contract parameters to use in designing contracts between the provider and residential customers, when to turn which power unit on or off and how much power to cut during peak demand hours. The model uses information on customer preferences for choice of contract parameters such as DLC financial incentives and energy usage curtailment. In numerical experiments, the proposed model leads to projected cost savings of the order of 20%, compared to a current benchmark model used in practice. We also quantify the impact of factors leading to cost savings and study characteristics of customers picked by different contracts. Second, we study a DLC program in a macro economic environment using a Computable General Equilibrium (CGE) model. A CGE model is used to study the impact of external factors such as policy and technology changes on different economic sectors. Here we differentiate customers based on their preference for DLC programs by using different values for price elasticity of demand for electricity commodity. Consequently, DLC program customers could substitute demand for electricity commodity with other commodities such as transportation sector. Price elasticity of demand is calculated using a novel methodology that incorporates customer preferences for DLC contracts from the first model. The calculation of elasticity based on our methodology is useful since the prices of commodities are not only determined by aggregate demand and supply but also by customers' relative preferences for commodities. In addition to this we quantify the indirect substitution and rebound effects on sectoral activity levels, incomes and prices based on customer differences, when DLC is implemented.

Prediction Models for Dynamic Demand Response

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

Aman, Saima; Frincu, Marc; Chelmis, Charalampos

2015-11-02

As Smart Grids move closer to dynamic curtailment programs, Demand Response (DR) events will become necessary not only on fixed time intervals and weekdays predetermined by static policies, but also during changing decision periods and weekends to react to real-time demand signals. Unique challenges arise in this context vis-a-vis demand prediction and curtailment estimation and the transformation of such tasks into an automated, efficient dynamic demand response (D 2R) process. While existing work has concentrated on increasing the accuracy of prediction models for DR, there is a lack of studies for prediction models for D 2R, which we address inmore » this paper. Our first contribution is the formal definition of D 2R, and the description of its challenges and requirements. Our second contribution is a feasibility analysis of very-short-term prediction of electricity consumption for D 2R over a diverse, large-scale dataset that includes both small residential customers and large buildings. Our third, and major contribution is a set of insights into the predictability of electricity consumption in the context of D 2R. Specifically, we focus on prediction models that can operate at a very small data granularity (here 15-min intervals), for both weekdays and weekends - all conditions that characterize scenarios for D 2R. We find that short-term time series and simple averaging models used by Independent Service Operators and utilities achieve superior prediction accuracy. We also observe that workdays are more predictable than weekends and holiday. Also, smaller customers have large variation in consumption and are less predictable than larger buildings. Key implications of our findings are that better models are required for small customers and for non-workdays, both of which are critical for D 2R. Also, prediction models require just few days’ worth of data indicating that small amounts of historical training data can be used to make reliable predictions, simplifying the complexity of big data challenge associated with D 2R.« less

Smart Grid Risk Management

NASA Astrophysics Data System (ADS)

Abad Lopez, Carlos Adrian

Current electricity infrastructure is being stressed from several directions -- high demand, unreliable supply, extreme weather conditions, accidents, among others. Infrastructure planners have, traditionally, focused on only the cost of the system; today, resilience and sustainability are increasingly becoming more important. In this dissertation, we develop computational tools for efficiently managing electricity resources to help create a more reliable and sustainable electrical grid. The tools we present in this work will help electric utilities coordinate demand to allow the smooth and large scale integration of renewable sources of energy into traditional grids, as well as provide infrastructure planners and operators in developing countries a framework for making informed planning and control decisions in the presence of uncertainty. Demand-side management is considered as the most viable solution for maintaining grid stability as generation from intermittent renewable sources increases. Demand-side management, particularly demand response (DR) programs that attempt to alter the energy consumption of customers either by using price-based incentives or up-front power interruption contracts, is more cost-effective and sustainable in addressing short-term supply-demand imbalances when compared with the alternative that involves increasing fossil fuel-based fast spinning reserves. An essential step in compensating participating customers and benchmarking the effectiveness of DR programs is to be able to independently detect the load reduction from observed meter data. Electric utilities implementing automated DR programs through direct load control switches are also interested in detecting the reduction in demand to efficiently pinpoint non-functioning devices to reduce maintenance costs. We develop sparse optimization methods for detecting a small change in the demand for electricity of a customer in response to a price change or signal from the utility, dynamic learning methods for scheduling the maintenance of direct load control switches whose operating state is not directly observable and can only be inferred from the metered electricity consumption, and machine learning methods for accurately forecasting the load of hundreds of thousands of residential, commercial and industrial customers. These algorithms have been implemented in the software system provided by AutoGrid, Inc., and this system has helped several utilities in the Pacific Northwest, Oklahoma, California and Texas, provide more reliable power to their customers at significantly reduced prices. Providing power to widely spread out communities in developing countries using the conventional power grid is not economically feasible. The most attractive alternative source of affordable energy for these communities is solar micro-grids. We discuss risk-aware robust methods to optimally size and operate solar micro-grids in the presence of uncertain demand and uncertain renewable generation. These algorithms help system operators to increase their revenue while making their systems more resilient to inclement weather conditions.

Thermal Profiling of Residential Energy Use

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

Albert, A; Rajagopal, R

This work describes a methodology for informing targeted demand-response (DR) and marketing programs that focus on the temperature-sensitive part of residential electricity demand. Our methodology uses data that is becoming readily available at utility companies-hourly energy consumption readings collected from "smart" electricity meters, as well as hourly temperature readings. To decompose individual consumption into a thermal-sensitive part and a base load (non-thermally-sensitive), we propose a model of temperature response that is based on thermal regimes, i.e., unobserved decisions of consumers to use their heating or cooling appliances. We use this model to extract useful benchmarks that compose thermal profiles ofmore » individual users, i.e., terse characterizations of the statistics of these users' temperature-sensitive consumption. We present example profiles generated using our model on real consumers, and show its performance on a large sample of residential users. This knowledge may, in turn, inform the DR program by allowing scarce operational and marketing budgets to be spent on the right users-those whose influencing will yield highest energy reductions-at the right time. We show that such segmentation and targeting of users may offer savings exceeding 100% of a random strategy.« less

Modeling Framework and Validation of a Smart Grid and Demand Response System for Wind Power Integration

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

Broeer, Torsten; Fuller, Jason C.; Tuffner, Francis K.

2014-01-31

Electricity generation from wind power and other renewable energy sources is increasing, and their variability introduces new challenges to the power system. The emergence of smart grid technologies in recent years has seen a paradigm shift in redefining the electrical system of the future, in which controlled response of the demand side is used to balance fluctuations and intermittencies from the generation side. This paper presents a modeling framework for an integrated electricity system where loads become an additional resource. The agent-based model represents a smart grid power system integrating generators, transmission, distribution, loads and market. The model incorporates generatormore » and load controllers, allowing suppliers and demanders to bid into a Real-Time Pricing (RTP) electricity market. The modeling framework is applied to represent a physical demonstration project conducted on the Olympic Peninsula, Washington, USA, and validation simulations are performed using actual dynamic data. Wind power is then introduced into the power generation mix illustrating the potential of demand response to mitigate the impact of wind power variability, primarily through thermostatically controlled loads. The results also indicate that effective implementation of Demand Response (DR) to assist integration of variable renewable energy resources requires a diversity of loads to ensure functionality of the overall system.« less

National Renewable Energy Laboratory (NREL) Topic 2 Final Report: End-to-End Communication and Control System to Support Clean Energy Technologies

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

Hudgins, Andrew P.; Carrillo, Ismael M.; Jin, Xin

This document is the final report of a two-year development, test, and demonstration project, 'Cohesive Application of Standards- Based Connected Devices to Enable Clean Energy Technologies.' The project was part of the National Renewable Energy Laboratory's (NREL's) Integrated Network Testbed for Energy Grid Research and Technology (INTEGRATE) initiative hosted at Energy Systems Integration Facility (ESIF). This project demonstrated techniques to control distribution grid events using the coordination of traditional distribution grid devices and high-penetration renewable resources and demand response. Using standard communication protocols and semantic standards, the project examined the use cases of high/low distribution voltage, requests for volt-ampere-reactive (VAR)more » power support, and transactive energy strategies using Volttron. Open source software, written by EPRI to control distributed energy resources (DER) and demand response (DR), was used by an advanced distribution management system (ADMS) to abstract the resources reporting to a collection of capabilities rather than needing to know specific resource types. This architecture allows for scaling both horizontally and vertically. Several new technologies were developed and tested. Messages from the ADMS based on the common information model (CIM) were developed to control the DER and DR management systems. The OpenADR standard was used to help manage grid events by turning loads off and on. Volttron technology was used to simulate a homeowner choosing the price at which to enter the demand response market. Finally, the ADMS used newly developed algorithms to coordinate these resources with a capacitor bank and voltage regulator to respond to grid events.« less

BEopt-CA (Ex) -- A Tool for Optimal Integration of EE/DR/ES+PV in Existing California Homes. Cooperative Research and Development Final Report, CRADA Number CRD-11-429

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

Christensen, Craig

Opportunities for combining energy efficiency, demand response, and energy storage with PV are often missed, because the required knowledge and expertise for these different technologies exist in separate organizations or individuals. Furthermore, there is a lack of quantitative tools to optimize energy efficiency, demand response and energy storage with PV, especially for existing buildings. Our goal is to develop a modeling tool, BEopt-CA (Ex), with capabilities to facilitate identification and implementation of a balanced integration of energy efficiency (EE), demand response (DR), and energy storage (ES) with photovoltaics (PV) within the residential retrofit market. To achieve this goal, we willmore » adapt and extend an existing tool -- BEopt -- that is designed to identify optimal combinations of efficiency and PV in new home designs. In addition, we will develop multifamily residential modeling capabilities for use in California, to facilitate integration of distributed solar power into the grid in order to maximize its value to California ratepayers. The project is follow-on research that leverages previous California Solar Initiative RD&D investment in the BEopt software. BEopt facilitates finding the least cost combination of energy efficiency and renewables to support integrated DSM (iDSM) and Zero Net Energy (ZNE) in California residential buildings. However, BEopt is currently focused on modeling single-family houses and does not include satisfactory capabilities for modeling multifamily homes. The project brings BEopt's existing modeling and optimization capabilities to multifamily buildings, including duplexes, triplexes, townhouses, flats, and low-rise apartment buildings.« less

Development and Demonstration of the Open Automated Demand Response Standard for the Residential Sector

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

Herter, Karen; Rasin, Josh; Perry, Tim

2009-11-30

The goal of this study was to demonstrate a demand response system that can signal nearly every customer in all sectors through the integration of two widely available and non- proprietary communications technologies--Open Automated Demand Response (OpenADR) over lnternet protocol and Utility Messaging Channel (UMC) over FM radio. The outcomes of this project were as follows: (1) a software bridge to allow translation of pricing signals from OpenADR to UMC; and (2) a portable demonstration unit with an lnternet-connected notebook computer, a portfolio of DR-enabling technologies, and a model home. The demonstration unit provides visitors the opportunity to send electricity-pricingmore » information over the lnternet (through OpenADR and UMC) and then watch as the model appliances and lighting respond to the signals. The integration of OpenADR and UMC completed and demonstrated in this study enables utilities to send hourly or sub-hourly electricity pricing information simultaneously to the residential, commercial and industrial sectors.« less

Real Time Pricing as a Default or Optional Service for C&ICustomers: A Comparative Analysis of Eight Case Studies

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

Barbose, Galen; Goldman, Charles; Bharvirkar, Ranjit

Demand response (DR) has been broadly recognized to be an integral component of well-functioning electricity markets, although currently underdeveloped in most regions. Among the various initiatives undertaken to remedy this deficiency, public utility commissions (PUC) and utilities have considered implementing dynamic pricing tariffs, such as real-time pricing (RTP), and other retail pricing mechanisms that communicate an incentive for electricity consumers to reduce their usage during periods of high generation supply costs or system reliability contingencies. Efforts to introduce DR into retail electricity markets confront a range of basic policy issues. First, a fundamental issue in any market context is howmore » to organize the process for developing and implementing DR mechanisms in a manner that facilitates productive participation by affected stakeholder groups. Second, in regions with retail choice, policymakers and stakeholders face the threshold question of whether it is appropriate for utilities to offer a range of dynamic pricing tariffs and DR programs, or just ''plain vanilla'' default service. Although positions on this issue may be based primarily on principle, two empirical questions may have some bearing--namely, what level of price response can be expected through the competitive retail market, and whether establishing RTP as the default service is likely to result in an appreciable level of DR? Third, if utilities are to have a direct role in developing DR, what types of retail pricing mechanisms are most appropriate and likely to have the desired policy impact (e.g., RTP, other dynamic pricing options, DR programs, or some combination)? Given a decision to develop utility RTP tariffs, three basic implementation issues require attention. First, should it be a default or optional tariff, and for which customer classes? Second, what types of tariff design is most appropriate, given prevailing policy objectives, wholesale market structure, ratemaking practices and standards, and customer preferences? Third, if a primary goal for RTP implementation is to induce DR, what types of supplemental activities are warranted to support customer participation and price response (e.g., interval metering deployment, customer education, and technical assistance)?« less

Answering the big questions about differential response in Colorado: safety and cost outcomes from a randomized controlled trial.

PubMed

Winokur, Marc; Ellis, Raquel; Drury, Ida; Rogers, John

2015-01-01

Over the past 20 years, jurisdictions across the United States have implemented differential response (DR), which provides child protective services with the flexibility to tailor their response to reports of child abuse or neglect based on the level of risk. Given the widespread adoption of DR, there has been an increasing demand from policymakers, practitioners, and community stakeholders to build the evidence base for this innovative child welfare approach. This study was designed to answer the big questions regarding the effect of differential response on child welfare outcomes and costs using a randomized controlled trial in five Colorado counties. Specifically, the study examined the safety outcomes and costs of families who were randomly assigned to either a family assessment response (FAR) or an investigation response (IR). According to the regression results, there were no differences between the tracks on measures of system re-involvement. However, survival analysis findings indicate that FAR families were 18% less likely, over time, to have a high risk assessment after their initial accepted referral than were IR families. The cost study revealed no differences between the tracks on initial costs for caseworker contacts, services, and out-of-home placements. However, the results suggest that follow-up costs for IR cases were significantly higher (p<0.001) than for FAR cases. The authors discuss policy and practice implications for jurisdictions considering DR. Copyright © 2014 Elsevier Ltd. All rights reserved.

Data-driven modeling, control and tools for cyber-physical energy systems

NASA Astrophysics Data System (ADS)

Behl, Madhur

Energy systems are experiencing a gradual but substantial change in moving away from being non-interactive and manually-controlled systems to utilizing tight integration of both cyber (computation, communications, and control) and physical representations guided by first principles based models, at all scales and levels. Furthermore, peak power reduction programs like demand response (DR) are becoming increasingly important as the volatility on the grid continues to increase due to regulation, integration of renewables and extreme weather conditions. In order to shield themselves from the risk of price volatility, end-user electricity consumers must monitor electricity prices and be flexible in the ways they choose to use electricity. This requires the use of control-oriented predictive models of an energy system's dynamics and energy consumption. Such models are needed for understanding and improving the overall energy efficiency and operating costs. However, learning dynamical models using grey/white box approaches is very cost and time prohibitive since it often requires significant financial investments in retrofitting the system with several sensors and hiring domain experts for building the model. We present the use of data-driven methods for making model capture easy and efficient for cyber-physical energy systems. We develop Model-IQ, a methodology for analysis of uncertainty propagation for building inverse modeling and controls. Given a grey-box model structure and real input data from a temporary set of sensors, Model-IQ evaluates the effect of the uncertainty propagation from sensor data to model accuracy and to closed-loop control performance. We also developed a statistical method to quantify the bias in the sensor measurement and to determine near optimal sensor placement and density for accurate data collection for model training and control. Using a real building test-bed, we show how performing an uncertainty analysis can reveal trends about inverse model accuracy and control performance, which can be used to make informed decisions about sensor requirements and data accuracy. We also present DR-Advisor, a data-driven demand response recommender system for the building's facilities manager which provides suitable control actions to meet the desired load curtailment while maintaining operations and maximizing the economic reward. We develop a model based control with regression trees algorithm (mbCRT), which allows us to perform closed-loop control for DR strategy synthesis for large commercial buildings. Our data-driven control synthesis algorithm outperforms rule-based demand response methods for a large DoE commercial reference building and leads to a significant amount of load curtailment (of 380kW) and over $45,000 in savings which is 37.9% of the summer energy bill for the building. The performance of DR-Advisor is also evaluated for 8 buildings on Penn's campus; where it achieves 92.8% to 98.9% prediction accuracy. We also compare DR-Advisor with other data driven methods and rank 2nd on ASHRAE's benchmarking data-set for energy prediction.

Nutritional regimens with periodically recurring phases of dietary restriction extend lifespan in Drosophila.

PubMed

Romey-Glüsing, Renja; Li, Yang; Hoffmann, Julia; von Frieling, Jakob; Knop, Mirjam; Pfefferkorn, Roxana; Bruchhaus, Iris; Fink, Christine; Roeder, Thomas

2018-04-01

Nutritional interventions such as caloric and dietary restriction increase lifespan in various animal models. To identify alternative and less demanding nutritional interventions that extend lifespan, we subjected fruit flies ( Drosophila melanogaster) to weekly nutritional regimens that involved alternating a conventional diet with dietary restriction. Short periods of dietary restriction (up to 2 d) followed by longer periods of a conventional diet yielded minimal increases in lifespan. We found that 3 or more days of contiguous dietary restriction (DR) was necessary to yield a lifespan extension similar to that observed with persistent DR. Female flies were more responsive to these interventions than males. Physiologic changes known to be associated with prolonged DR, such as reduced metabolic rates, showed the same time course as lifespan extension. Moreover, concurrent transcriptional changes indicative of reduced insulin signaling were identified with DR. These physiologic and transcriptional changes were sustained, as they were detectable several days after switching to conventional diets. Taken together, diets with longer periods of DR extended lifespan concurrently with physiologic and transcriptional changes that may underlie this increase in lifespan.-Romey-Glüsing, R., Li, Y., Hoffmann, J., von Frieling, J., Knop, M., Pfefferkorn, R., Bruchhaus, I., Fink, C., Roeder, T. Nutritional regimens with periodically recurring phases of dietary restriction extend lifespan in Drosophila.

Smart Meter Driven Segmentation: What Your Consumption Says About You

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

Albert, A; Rajagopal, R

With the rollout of smart metering infrastructure at scale, demand-response (DR) programs may now be tailored based on users' consumption patterns as mined from sensed data. For issuing DR events it is key to understand the inter-temporal consumption dynamics as to appropriately segment the user population. We propose to infer occupancy states from consumption time series data using a hidden Markov model framework. Occupancy is characterized in this model by 1) magnitude, 2) duration, and 3) variability. We show that users may be grouped according to their consumption patterns into groups that exhibit qualitatively different dynamics that may be exploitedmore » for program enrollment purposes. We investigate empirically the information that residential energy consumers' temporal energy demand patterns characterized by these three dimensions may convey about their demographic, household, and appliance stock characteristics. Our analysis shows that temporal patterns in the user's consumption data can predict with good accuracy certain user characteristics. We use this framework to argue that there is a large degree of individual predictability in user consumption at a population level.« less

Distributed Energy Systems Integration and Demand Optimization for Autonomous Operations and Electric Grid Transactions

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

Ghatikar, Girish; Mashayekh, Salman; Stadler, Michael

Distributed power systems in the U.S. and globally are evolving to provide reliable and clean energy to consumers. In California, existing regulations require significant increases in renewable generation, as well as identification of customer-side distributed energy resources (DER) controls, communication technologies, and standards for interconnection with the electric grid systems. As DER deployment expands, customer-side DER control and optimization will be critical for system flexibility and demand response (DR) participation, which improves the economic viability of DER systems. Current DER systems integration and communication challenges include leveraging the existing DER and DR technology and systems infrastructure, and enabling optimized cost,more » energy and carbon choices for customers to deploy interoperable grid transactions and renewable energy systems at scale. Our paper presents a cost-effective solution to these challenges by exploring communication technologies and information models for DER system integration and interoperability. This system uses open standards and optimization models for resource planning based on dynamic-pricing notifications and autonomous operations within various domains of the smart grid energy system. It identifies architectures and customer engagement strategies in dynamic DR pricing transactions to generate feedback information models for load flexibility, load profiles, and participation schedules. The models are tested at a real site in California—Fort Hunter Liggett (FHL). Furthermore, our results for FHL show that the model fits within the existing and new DR business models and networked systems for transactive energy concepts. Integrated energy systems, communication networks, and modeling tools that coordinate supply-side networks and DER will enable electric grid system operators to use DER for grid transactions in an integrated system.« less

The Dominican Republic-Central American Free Trade Agreement (DR-CAFTA): Understanding the Reasons Why the Dominican Republic (DR) Joined the CAFTA Negotiations

DTIC Science & Technology

2009-06-01

the major issues that the DR faced was how to protect itself from imported U.S. beverages that contained high fructose corn syrup . Many Dominican... corn syrup as a sweetener.204 This was a controversial move, which gained support in the DR Congress after many sugar producers demanded increased...protection from foreign imports. The producers claimed that the introduction of imported corn syrup sweetened beverages would cause an approximate

Evaluation of the Demand Response Performance of Electric Water Heaters

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

Mayhorn, Ebony T.; Widder, Sarah H.; Parker, Steven A.

2015-03-17

The purpose of this project is to verify or refute many of the concerns raised by utilities regarding the ability of large tank HPWHs to perform DR by measuring the performance of HPWHs compared to ERWHs in providing DR services. perform DR by measuring the performance of HPWHs compared to ERWHs in providing DR services. This project was divided into three phases. Phase 1 consisted of week-long laboratory experiments designed to demonstrate technical feasibility of individual large-tank HPWHs in providing DR services compared to large-tank ERWHs. In Phase 2, the individual behaviors of the water heaters were then extrapolated tomore » a population by first calibrating readily available water heater models developed in GridLAB-D simulation software to experimental results obtained in Phase 1. These models were used to simulate a population of water heaters and generate annual load profiles to assess the impacts on system-level power and residential load curves. Such population modeling allows for the inherent and permanent load reduction accomplished by the more efficient HPWHs to be considered, in addition to the temporal DR services the water heater can provide by switching ON or OFF as needed by utilities. The economic and emissions impacts of using large-tank water heaters in DR programs are then analyzed from the utility and consumer perspective, based on National Impacts Analysis in Phase 3. Phase 1 is discussed in this report. Details on Phases 2 and 3 can be found in the companion report (Cooke et al. 2014).« less

Research on intelligent power consumption strategy based on time-of-use pricing

NASA Astrophysics Data System (ADS)

Fu, Wei; Gong, Li; Chen, Heli; He, Yu

2017-06-01

In this paper, through the analysis of shortcomings of the current domestic and foreign household power consumption strategy: Passive way of power consumption, ignoring the different priority of electric equipment, neglecting the actual load pressure of the grid, ignoring the interaction with the user, to decrease the peak-valley difference and improve load curve in residential area by demand response (DR technology), an intelligent power consumption scheme based on time-of-use(TOU) pricing for household appliances is proposed. The main contribution of this paper is: (1) Three types of household appliance loads are abstracted from different operating laws of various household appliances, and the control models and DR strategies corresponding to these types are established. (2) The fuzzified processing for the information of TOU price, which is based on the time intervals, is performed to get the price priority, in accordance with such DR events as the maximum restricted load of DR, the time of DR and the duration of interruptible load and so on, the DR control rule and pre-scheduling mechanism are led in. (3) The dispatching sequence of household appliances in the control and scheduling queue are switched and controlled to implement the equilibrium of peak and valley loads. The equilibrium effects and economic benefits of power system by pre-scheduling and DR dispatching are compared and analyzed by simulation example, and the results show that using the proposed household appliance control (HAC) scheme the overall cost of consumers can be reduced and the power system load can be alleviated, so the proposed household appliance control (HAC) scheme is feasible and reasonable.

Grid Connected Functionality

DOE Data Explorer

Baker, Kyri; Jin, Xin; Vaidynathan, Deepthi; Jones, Wesley; Christensen, Dane; Sparn, Bethany; Woods, Jason; Sorensen, Harry; Lunacek, Monte

2016-08-04

Dataset demonstrating the potential benefits that residential buildings can provide for frequency regulation services in the electric power grid. In a hardware-in-the-loop (HIL) implementation, simulated homes along with a physical laboratory home are coordinated via a grid aggregator, and it is shown that their aggregate response has the potential to follow the regulation signal on a timescale of seconds. Connected (communication-enabled), devices in the National Renewable Energy Laboratory's (NREL's) Energy Systems Integration Facility (ESIF) received demand response (DR) requests from a grid aggregator, and the devices responded accordingly to meet the signal while satisfying user comfort bounds and physical hardware limitations.

Hardware-in-the-Loop Simulation of a Distribution System with Air Conditioners under Model Predictive Control: Preprint

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

Sparn, Bethany F; Ruth, Mark F; Krishnamurthy, Dheepak

Many have proposed that responsive load provided by distributed energy resources (DERs) and demand response (DR) are an option to provide flexibility to the grid and especially to distribution feeders. However, because responsive load involves a complex interplay between tariffs and DER and DR technologies, it is challenging to test and evaluate options without negatively impacting customers. This paper describes a hardware-in-the-loop (HIL) simulation system that has been developed to reduce the cost of evaluating the impact of advanced controllers (e.g., model predictive controllers) and technologies (e.g., responsive appliances). The HIL simulation system combines large-scale software simulation with a smallmore » set of representative building equipment hardware. It is used to perform HIL simulation of a distribution feeder and the loads on it under various tariff structures. In the reported HIL simulation, loads include many simulated air conditioners and one physical air conditioner. Independent model predictive controllers manage operations of all air conditioners under a time-of-use tariff. Results from this HIL simulation and a discussion of future development work of the system are presented.« less

Field Experience with and Potential for Multi-time Scale Grid Transactions from Responsive Commercial Buildings

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

Piette, Mary Ann; Kiliccote, Sila; Ghatikar, Girish

2014-08-01

The need for and concepts behind demand response are evolving. As the electric system changes with more intermittent renewable electric supply systems, there is a need to allow buildings to provide more flexible demand. This paper presents results from field studies and pilots, as well as engineering estimates of the potential capabilities of fast load responsiveness in commercial buildings. We present a sector wide analysis of flexible loads in commercial buildings, which was conducted to improve resource planning and determine which loads to evaluate in future demonstrations. These systems provide important capabilities for future transactional systems. The field analysis ismore » based on results from California, plus projects in the northwest and east coast. End-uses considered include heating, ventilation, air conditioning and lighting. The timescales of control include day-ahead, as well as day-of, 10-minute ahead and even faster response. This technology can provide DR signals on different times scales to interact with responsive building loads. We describe the latency of the control systems in the building and the round trip communications with the wholesale grid operators.« less

Expression of Histophilus somni IbpA DR2 protective antigen in the diatom Thalassiosira pseudonana.

PubMed

Davis, Aubrey; Crum, Lauren T; Corbeil, Lynette B; Hildebrand, Mark

2017-07-01

Increasing demand for the low-cost production of valuable proteins has stimulated development of novel expression systems. Many challenges faced by existing technology may be overcome by using unicellular microalgae as an expression platform due to their ability to be cultivated rapidly, inexpensively, and in large scale. Diatoms are a particularly productive type of unicellular algae showing promise as production organisms. Here, we report the development of an expression system in the diatom Thalassiosira pseudonana by expressing the protective IbpA DR2 antigen from Histophilus somni for the production of a vaccine against bovine respiratory disease. The utilization of diatoms with their typically silicified cell walls permitted development of silicon-responsive transcription elements to induce protein expression. Specifically, we demonstrate that transcription elements from the silicon transporter gene SIT1 are sufficient to drive high levels of IbpA DR2 expression during silicon limitation and growth arrest. These culture conditions eliminate the flux of cellular resources into cell division processes, yet do not limit protein expression. In addition to improving protein expression levels by molecular manipulations, yield was dramatically increased through cultivation enhancement including elevated light and CO 2 supplementation. We substantially increased recombinant protein production over starting levels to 1.2% of the total sodium dodecyl sulfate-extractable protein in T. pseudonana, which was sufficient to conduct preliminary immunization trials in mice. Mice exposed to 5 μg of diatom-expressed DR2 in whole or sonicated cells (without protein purification) exhibited a modest immune response without the addition of adjuvant.

Expression Analysis of Dopamine Receptor Subtypes in Normal Human Pituitaries, Nonfunctioning Pituitary Adenomas and Somatotropinomas, and the Association between Dopamine and Somatostatin Receptors with Clinical Response to Octreotide-LAR in Acromegaly

PubMed Central

Neto, Leonardo Vieira; Machado, Evelyn de O.; Luque, Raul M.; Taboada, Giselle F.; Marcondes, Jorge B.; Chimelli, Leila M. C.; Quintella, Leonardo Pereira; Niemeyer, Paulo; de Carvalho, Denise P.; Kineman, Rhonda D.; Gadelha, Mônica R.

2009-01-01

Context: Dopamine receptor (DR) and somatostatin receptor subtype expression in pituitary adenomas may predict the response to postsurgical therapies. Objectives: Our objectives were to assess and compare the mRNA levels of DR1-5 and somatostatin receptors 1–5 in normal pituitaries (NPs), nonfunctioning pituitary adenomas (NFPAs), and somatotropinomas. In addition, we determined whether the level of DR expression correlates with the in vivo response to octreotide-LAR in acromegalic patients. Design and Patients: Eight NPs, 30 NFPAs, and 39 somatotropinomas were analyzed for receptor mRNA levels by real-time RT-PCR. The DR2 short variant was estimated as the DR2 long/DR2 total (DR2T). The relationship between DR expression and the postsurgical response to octreotide-LAR was assessed in 19 of the acromegalic patients. Results: DR3 was not detected. The relationship between expression levels of DR subtypes in NPs and somatotropinomas was DR2T⋙DR4≫DR5>DR1, whereas in NFPAs, DR2T⋙DR4≫DR1>DR5. The DR2 short variant was the predominant DR2 variant in the majority of samples. In acromegalics treated with octreotide-LAR, DR1 was negatively correlated with percent GH reduction (3 months: r = −0.67, P = 0.002; and 6 months: r = −0.58, P = 0.009), and DR5 was positively correlated with percent IGF-I reduction (3 months: r = 0.55, P = 0.01; and 6 months: r = 0.47, P = 0.04). Conclusions: DR2 is the predominant DR subtype in NPs, NFPAs, and somatotropinomas. The fact that DR1, DR4, and DR5 are also expressed in many adenomas tested suggests that these receptors might also play a role in the therapeutic impact of postsurgical medical therapies in patients with NFPA and acromegaly. This was supported by the finding that the in vivo response to octreotide-LAR was negatively associated with DR1 and positively associated with DR5. PMID:19293270

A survey of diagnostic radiology residency program directors and the increasing demands of program leadership.

PubMed

Webber, Grant R; Baumgarten, Deborah A; Chen, Zhengjia; Wang, Zhibo; Mullins, Mark E

2013-07-01

The aim of this study was to identify trends and opinions with respect to leadership turnover, leadership responsibilities, and residency requirements. Program directors (PDs) of diagnostic radiology (DR) residency programs were identified via the ACGME and the Fellowship and Residency Electronic Interactive Database, along with a programmatic website search. A web-based survey was e-mailed, with questions concerning lengths of time the current and prior PDs held their positions, residency size, amounts of time spent on and lengths of current and past Program Information Forms, and opinions on how the position has changed and how metrics, outcomes, and documentation may be affecting teaching, resident education, and patient care. Thirty-two percent (60 of 186) of US DR residency PDs answered at least 1 of the survey questions. The average length of time the current PDs held their positions was shorter compared with the previous PDs, and it has taken longer and required more pages to complete the current Program Information Forms compared with prior cycles. The majority of respondents felt that the job of PD was harder than 5 years ago and that turnover among PDs is a "current/impending" problem. The majority of respondents felt that time spent on metrics, outcomes, and documentation is taking away from teaching, learning, and taking care of patients. Many DR residency PDs have recognized increased administrative burdens in recent years. Some feel that these increased demands may in part have negative effects on resident education and patient care. Copyright © 2013 American College of Radiology. Published by Elsevier Inc. All rights reserved.

The NASA Ames Fatigue Countermeasures Program: The Next Generation

NASA Technical Reports Server (NTRS)

Rosekind, Mark R.; Neri, David F.; Miller, Donna L.; Gregory, Kevin B.; Webbon, Lissa L.; Oyung, Ray L.

1997-01-01

Twenty-four hour, global aviation operations pose unique challenges to humans. Physiological requirements related to sleep, the internal circadian clock, and human fatigue are critical factors that are known to affect safety, performance, and productivity. Understanding the human operators' physiological capabilities, and limitations, will be important to address these issues as global demand for aviation activities continues to increase. In 1980, in response to a Congressional request, the National Aeronautics and Space Administration (NASA) Ames Research Center initiated a Fatigue/Jet Lag Program to examine the role of fatigue in flight operations. Originally established by Dr. John K. Lauber and Dr. Charles E. Billings, the Program was designed to address three objectives: (1) determine the extent of fatigue, sleep loss, and circadian disruption in flight operations; (2) determine how fatigue affected flight crew performance; and (3) develop strategies to maximize performance and alertness during flight operations.

ISAAC Photometric Comparison of ECLIPSE Jitter and the ORAC-DR Equivalent Recipe for ISAAC

NASA Astrophysics Data System (ADS)

Currie, M. J.

2005-12-01

Motivated by a request from astronomers demanding accurate and consistent infrared photometry, I compare the photometry and quality of mosaics generated by the ECLIPSE jitter task and the ORAC-DR JITTER_SELF_FLAT recipe in two fields. The current (v4.9.0) ECLIPSE produces photometry a few percent fainter than ORAC-DR; the systematic trend with magnitude seen in v4.4.1 is now removed. Random errors arising from poor flat-fielding are not resolved. ECLIPSE generates noisier mosaics; ORAC-DR has poorer bias removal in crowded fields and defaults to larger mosaics. ORAC-DR runs a few times slower than ECLIPSE, but its recipe development is measured in weeks, not years.

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

Auslander, David; Culler, David; Wright, Paul

The goal of the 2.5 year Distributed Intelligent Automated Demand Response (DIADR) project was to reduce peak electricity load of Sutardja Dai Hall at UC Berkeley by 30% while maintaining a healthy, comfortable, and productive environment for the occupants. We sought to bring together both central and distributed control to provide “deep” demand response1 at the appliance level of the building as well as typical lighting and HVAC applications. This project brought together Siemens Corporate Research and Siemens Building Technology (the building has a Siemens Apogee Building Automation System (BAS)), Lawrence Berkeley National Laboratory (leveraging their Open Automated Demand Responsemore » (openADR), Auto-­Demand Response, and building modeling expertise), and UC Berkeley (related demand response research including distributed wireless control, and grid-­to-­building gateway development). Sutardja Dai Hall houses the Center for Information Technology Research in the Interest of Society (CITRIS), which fosters collaboration among industry and faculty and students of four UC campuses (Berkeley, Davis, Merced, and Santa Cruz). The 141,000 square foot building, occupied in 2009, includes typical office spaces and a nanofabrication laboratory. Heating is provided by a district heating system (steam from campus as a byproduct of the campus cogeneration plant); cooling is provided by one of two chillers: a more typical electric centrifugal compressor chiller designed for the cool months (Nov-­ March) and a steam absorption chiller for use in the warm months (April-­October). Lighting in the open office areas is provided by direct-­indirect luminaries with Building Management System-­based scheduling for open areas, and occupancy sensors for private office areas. For the purposes of this project, we focused on the office portion of the building. Annual energy consumption is approximately 8053 MWh; the office portion is estimated as 1924 MWh. The maximum peak load during the study period was 1175 kW. Several new tools facilitated this work, such as the Smart Energy Box, the distributed load controller or Energy Information Gateway, the web-­based DR controller (dubbed the Central Load-­Shed Coordinator or CLSC), and the Demand Response Capacity Assessment & Operation Assistance Tool (DRCAOT). In addition, an innovative data aggregator called sMAP (simple Measurement and Actuation Profile) allowed data from different sources collected in a compact form and facilitated detailed analysis of the building systems operation. A smart phone application (RAP or Rapid Audit Protocol) facilitated an inventory of the building’s plug loads. Carbon dioxide sensors located in conference rooms and classrooms allowed demand controlled ventilation. The extensive submetering and nimble access to this data provided great insight into the details of the building operation as well as quick diagnostics and analyses of tests. For example, students discovered a short-­cycling chiller, a stuck damper, and a leaking cooling coil in the first field tests. For our final field tests, we were able to see how each zone was affected by the DR strategies (e.g., the offices on the 7th floor grew very warm quickly) and fine-­tune the strategies accordingly.« less

Epitope Analysis of the Collagen Type V-Specific T Cell Response in Lung Transplantation Reveals an HLA-DRB1*15 Bias in Both Recipient and Donor

PubMed Central

Keller, Melissa R.; Haynes, Lynn D.; Jankowska-Gan, Ewa; Sullivan, Jeremy A.; Agashe, Vrushali V.; Burlingham, Scott R.; Burlingham, William J.

2013-01-01

Background IL-17-dependent cellular immune responses to the α1 chain of collagen type V are associated with development of bronchiolitis obliterans syndrome after lung transplantation, and with idiopathic pulmonary fibrosis and coronary artery disease, primary indications for lung or heart transplantation, respectively. Methodology/Principal Findings We found that 30% of the patients awaiting lung transplantation exhibited a strong cell-mediated immune response to col(V). Of these, 53% expressed HLA-DR15, compared to a 28% HLA-DR15 frequency in col(V) low-responders (p=0.02). After transplantation, patients with HLA-DR1 and -DR17, not -DR15, developed anti-col(V) responses most frequently (p=0.04 and 0.01 vs. controls, respectively). However, recipients of a lung from an HLA-DR15+ donor were at significantly elevated risk of developing anti-col(V) responses (p=0.02) and BOS (p=0.03). To determine the molecular basis of this unusual pattern of DR allele bias, a peptide library comprising the collagenous region of the α1(V) protein was screened for binding to HLA-DR0101, -DR1501, -DR0301 (DR17) or to HLA-DQ2 (DQA1*0501: DQB1*0201; in linkage disequilibrium with -DR17) and -DQ6 (DQA1*0102: DQB1*0602; linked to -DR15). Eight 15-mer peptides, six DR-binding and two DQ-binding, were identified. HLA-DR15 binding to two peptides yielded the highest binding scores: 650 (where 100 = positive control) for p799 (GIRGLKGTKGEKGED), and 193 for p1439 (LRGIPGPVGEQGLPG). These peptides, which also bound weakly to HLA-DR1, elicited responses in both HLA-DR1+ and -DR15+ col(V) reactive hosts, whereas binding and immunoreactivity of p1049 (KDGPPGLRGFPGDRG) was DR15-specific. Remarkably, a col(V)-reactive HLA-DR1+DR15neg lung transplant patient, whose donor was HLA-DR15+, responded not only to p799 and p1439, but also to p1049. Conclusions/Significance HLA-DR15 and IPF disease were independently associated with pre-transplant col(V) autoimmunity. The increased risk of de novo immunity to col(V) and BOS, associated with receiving a lung transplant from an HLA-DR15+ donor, may result from presentation by donor-derived HLA- DR15, of novel self-peptides to recipient T cells. PMID:24265781

The Story Behind the Story: Falling out of the Tree of Life

ERIC Educational Resources Information Center

Sis, Peter

2004-01-01

In this article, the author shares some of the background material that did not make it into his biography of Charles Darwin, "The Tree of Life." Specifically, he discusses the important role that teachers played in Darwin's life, from his demanding father (Dr. Darwin) to zoologist Dr. Robert Grant and taxidermist John Edmonstone (a freed slave).

DR5 as a reporter system to study auxin response in Populus.

PubMed

Chen, Yiru; Yordanov, Yordan S; Ma, Cathleen; Strauss, Steven; Busov, Victor B

2013-03-01

KEY MESSAGE : Auxin responsive promoter DR5 reporter system is functional in Populus to monitor auxin response in tissues including leaves, roots, and stems. We described the behavior of the DR5::GUS reporter system in stably transformed Populus plants. We found several similarities with Arabidopsis, including sensitivity to native and synthetic auxins, rapid induction after treatment in a variety of tissues, and maximal responses in root tissues. There were also several important differences from Arabidopsis, including slower time to maximum response and lower induction amplitude. Young leaves and stem sections below the apex showed much higher DR5 activity than did older leaves and stems undergoing secondary growth. DR5 activity was highest in cortex, suggesting high levels of auxin concentration and/or sensitivity in this tissue. Our study shows that the DR5 reporter system is a sensitive and facile system for monitoring auxin responses and distribution at cellular resolution in poplar.

Energy management and control of active distribution systems

NASA Astrophysics Data System (ADS)

Shariatzadeh, Farshid

Advancements in the communication, control, computation and information technologies have driven the transition to the next generation active power distribution systems. Novel control techniques and management strategies are required to achieve the efficient, economic and reliable grid. The focus of this work is energy management and control of active distribution systems (ADS) with integrated renewable energy sources (RESs) and demand response (DR). Here, ADS mean automated distribution system with remotely operated controllers and distributed energy resources (DERs). DER as active part of the next generation future distribution system includes: distributed generations (DGs), RESs, energy storage system (ESS), plug-in hybrid electric vehicles (PHEV) and DR. Integration of DR and RESs into ADS is critical to realize the vision of sustainability. The objective of this dissertation is the development of management architecture to control and operate ADS in the presence of DR and RES. One of the most challenging issues for operating ADS is the inherent uncertainty of DR and RES as well as conflicting objective of DER and electric utilities. ADS can consist of different layers such as system layer and building layer and coordination between these layers is essential. In order to address these challenges, multi-layer energy management and control architecture is proposed with robust algorithms in this work. First layer of proposed multi-layer architecture have been implemented at the system layer. Developed AC optimal power flow (AC-OPF) generates fair price for all DR and non-DR loads which is used as a control signal for second layer. Second layer controls DR load at buildings using a developed look-ahead robust controller. Load aggregator collects information from all buildings and send aggregated load to the system optimizer. Due to the different time scale at these two management layers, time coordination scheme is developed. Robust and deterministic controllers are developed to maximize the energy usage from rooftop photovoltaic (PV) generation locally and minimize heat-ventilation and air conditioning (HVAC) consumption while maintaining inside temperature within comfort zone. The performance of the developed multi-layer architecture has been analyzed using test case studies and results show the robustness of developed controller in the presence of uncertainty.

Establishment of HLA-DR4 Transgenic Mice for the Identification of CD4+ T Cell Epitopes of Tumor-Associated Antigens

PubMed Central

Harada, Kumiko; Michibata, Yayoi; Tsukamoto, Hirotake; Senju, Satoru; Tomita, Yusuke; Yuno, Akira; Hirayama, Masatoshi; Abu Sayem, Mohammad; Takeda, Naoki; Shibuya, Isao; Sogo, Shinji; Fujiki, Fumihiro; Sugiyama, Haruo; Eto, Masatoshi; Nishimura, Yasuharu

2013-01-01

Reports have shown that activation of tumor-specific CD4+ helper T (Th) cells is crucial for effective anti-tumor immunity and identification of Th-cell epitopes is critical for peptide vaccine-based cancer immunotherapy. Although computer algorithms are available to predict peptides with high binding affinity to a specific HLA class II molecule, the ability of those peptides to induce Th-cell responses must be evaluated. We have established HLA-DR4 (HLA-DRA*01:01/HLA-DRB1*04:05) transgenic mice (Tgm), since this HLA-DR allele is most frequent (13.6%) in Japanese population, to evaluate HLA-DR4-restricted Th-cell responses to tumor-associated antigen (TAA)-derived peptides predicted to bind to HLA-DR4. To avoid weak binding between mouse CD4 and HLA-DR4, Tgm were designed to express chimeric HLA-DR4/I-Ed, where I-Ed α1 and β1 domains were replaced with those from HLA-DR4. Th cells isolated from Tgm immunized with adjuvant and HLA-DR4-binding cytomegalovirus-derived peptide proliferated when stimulated with peptide-pulsed HLA-DR4-transduced mouse L cells, indicating chimeric HLA-DR4/I-Ed has equivalent antigen presenting capacity to HLA-DR4. Immunization with CDCA155-78 peptide, a computer algorithm-predicted HLA-DR4-binding peptide derived from TAA CDCA1, successfully induced Th-cell responses in Tgm, while immunization of HLA-DR4-binding Wilms' tumor 1 antigen-derived peptide with identical amino acid sequence to mouse ortholog failed. This was overcome by using peptide-pulsed syngeneic bone marrow-derived dendritic cells (BM-DC) followed by immunization with peptide/CFA booster. BM-DC-based immunization of KIF20A494-517 peptide from another TAA KIF20A, with an almost identical HLA-binding core amino acid sequence to mouse ortholog, successfully induced Th-cell responses in Tgm. Notably, both CDCA155-78 and KIF20A494-517 peptides induced human Th-cell responses in PBMCs from HLA-DR4-positive donors. Finally, an HLA-DR4 binding DEPDC1191-213 peptide from a new TAA DEPDC1 overexpressed in bladder cancer induced strong Th-cell responses both in Tgm and in PBMCs from an HLA-DR4-positive donor. Thus, the HLA-DR4 Tgm combined with computer algorithm was useful for preliminary screening of candidate peptides for vaccination. PMID:24386437

Sex differences in corticotropin-releasing factor receptor-1 action within the dorsal raphe nucleus in stress responsivity.

PubMed

Howerton, Alexis R; Roland, Alison V; Fluharty, Jessica M; Marshall, Anikò; Chen, Alon; Daniels, Derek; Beck, Sheryl G; Bale, Tracy L

2014-06-01

Women are twice as likely as men to suffer from stress-related affective disorders. Corticotropin-releasing factor (CRF) is an important link between stress and mood, in part through its signaling in the serotonergic dorsal raphe (DR). Development of CRF receptor-1 (CRFr1) antagonists has been a focus of numerous clinical trials but has not yet been proven efficacious. We hypothesized that sex differences in CRFr1 modulation of DR circuits might be key determinants in predicting therapeutic responses and affective disorder vulnerability. Male and female mice received DR infusions of the CRFr1 antagonist, NBI 35965, or CRF and were evaluated for stress responsivity. Sex differences in indices of neural activation (cFos) and colocalization of CRFr1 throughout the DR were examined. Whole-cell patch-clamp electrophysiology assessed sex differences in serotonin neuron membrane characteristics and responsivity to CRF. Males showed robust behavioral and hypothalamic-pituitary-adrenal axis responses to DR infusion of NBI 35965 and CRF, whereas females were minimally responsive. Sex differences were also found for both CRF-induced DR cFos and CRFr1 co-localization throughout the DR. Electrophysiologically, female serotonergic neurons showed blunted membrane excitability and divergent inhibitory postsynaptic current responses to CRF application. These studies demonstrate convincing sex differences in CRFr1 activity in the DR, where blunted female responses to NBI 35965 and CRF suggest unique stress modulation of the DR. These sex differences might underlie affective disorder vulnerability and differential sensitivity to pharmacologic treatments developed to target the CRF system, thereby contributing to a current lack of CRFr1 antagonist efficacy in clinical trials. © 2013 Published by Society of Biological Psychiatry on behalf of Society of Biological Psychiatry.

Obligations and frustrations with high-risk patients: ethics of physicians' evaluations.

PubMed

Jones, James W; McCullough, Laurence B

2015-02-01

A surgeon, Dr A. Droit, has been following a 97-year-old male with a type IV thoracoabdominal aneurysm, which became symptomatic this morning and is leaking. The patient is frail but active with no important comorbidities. The anatomy demands an open procedure. The patient is a former renowned physician who has been a longtime family friend of Dr Droit-like a grandfather. He presented incoherent with sagging blood pressure. A complicating factor is that Dr D. Rag, the chief anesthesiologist, decided that neither he nor any of his staff would provide anesthesia. Dr Droit knows an anesthesiologist who handles high-risk patients at another hospital in the medical center. The patient has worsened over the last hour, is becoming more unstable, and is unable to respond but his wife wishes to consent for surgery. What should Dr Droit do? Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Diabetic Retinopathy: Vascular and Inflammatory Disease

PubMed Central

Semeraro, F.; Cancarini, A.; dell'Omo, R.; Rezzola, S.; Romano, M. R.; Costagliola, C.

2015-01-01

Diabetic retinopathy (DR) is the leading cause of visual impairment in the working-age population of the Western world. The pathogenesis of DR is complex and several vascular, inflammatory, and neuronal mechanisms are involved. Inflammation mediates structural and molecular alterations associated with DR. However, the molecular mechanisms underlying the inflammatory pathways associated with DR are not completely characterized. Previous studies indicate that tissue hypoxia and dysregulation of immune responses associated with diabetes mellitus can induce increased expression of numerous vitreous mediators responsible for DR development. Thus, analysis of vitreous humor obtained from diabetic patients has made it possible to identify some of the mediators (cytokines, chemokines, and other factors) responsible for DR pathogenesis. Further studies are needed to better understand the relationship between inflammation and DR. Herein the main vitreous-related factors triggering the occurrence of retinal complication in diabetes are highlighted. PMID:26137497

Response to the Hughes et al. Paper on Differential Response

ERIC Educational Resources Information Center

Baird, Christopher; Park, Katherine; Lohrbach, Suzanne

2013-01-01

Ronald Hughes, Judith Rycus, and their colleagues have produced a seminal review of differential response (DR) programs implemented across the nation. Their review questions nearly every aspect of the DR movement, beginning with the concept on which all DR programs are based and ending with serious concerns about the quality of evaluations…

Dietary Restriction Affects Neuronal Response Property and GABA Synthesis in the Primary Visual Cortex.

PubMed

Yang, Jinfang; Wang, Qian; He, Fenfen; Ding, Yanxia; Sun, Qingyan; Hua, Tianmiao; Xi, Minmin

2016-01-01

Previous studies have reported inconsistent effects of dietary restriction (DR) on cortical inhibition. To clarify this issue, we examined the response properties of neurons in the primary visual cortex (V1) of DR and control groups of cats using in vivo extracellular single-unit recording techniques, and assessed the synthesis of inhibitory neurotransmitter GABA in the V1 of cats from both groups using immunohistochemical and Western blot techniques. Our results showed that the response of V1 neurons to visual stimuli was significantly modified by DR, as indicated by an enhanced selectivity for stimulus orientations and motion directions, decreased visually-evoked response, lowered spontaneous activity and increased signal-to-noise ratio in DR cats relative to control cats. Further, it was shown that, accompanied with these changes of neuronal responsiveness, GABA immunoreactivity and the expression of a key GABA-synthesizing enzyme GAD67 in the V1 were significantly increased by DR. These results demonstrate that DR may retard brain aging by increasing the intracortical inhibition effect and improve the function of visual cortical neurons in visual information processing. This DR-induced elevation of cortical inhibition may favor the brain in modulating energy expenditure based on food availability.

Dietary Restriction Affects Neuronal Response Property and GABA Synthesis in the Primary Visual Cortex

PubMed Central

Sun, Qingyan; Hua, Tianmiao; Xi, Minmin

2016-01-01

Previous studies have reported inconsistent effects of dietary restriction (DR) on cortical inhibition. To clarify this issue, we examined the response properties of neurons in the primary visual cortex (V1) of DR and control groups of cats using in vivo extracellular single-unit recording techniques, and assessed the synthesis of inhibitory neurotransmitter GABA in the V1 of cats from both groups using immunohistochemical and Western blot techniques. Our results showed that the response of V1 neurons to visual stimuli was significantly modified by DR, as indicated by an enhanced selectivity for stimulus orientations and motion directions, decreased visually-evoked response, lowered spontaneous activity and increased signal-to-noise ratio in DR cats relative to control cats. Further, it was shown that, accompanied with these changes of neuronal responsiveness, GABA immunoreactivity and the expression of a key GABA-synthesizing enzyme GAD67 in the V1 were significantly increased by DR. These results demonstrate that DR may retard brain aging by increasing the intracortical inhibition effect and improve the function of visual cortical neurons in visual information processing. This DR-induced elevation of cortical inhibition may favor the brain in modulating energy expenditure based on food availability. PMID:26863207

Parallel, Real-Time and Pipeline Data Reduction for the ROVER Sub-mm Heterodyne Polarimeter on the JCMT with ACSIS and ORAC-DR

NASA Astrophysics Data System (ADS)

Leech, J.; Dewitt, S.; Jenness, T.; Greaves, J.; Lightfoot, J. F.

2005-12-01

ROVER is a rotating waveplate polarimeter for use with (sub)mm heterodyne instruments, particularly the 16 element focal plane Heterodyne Array Receiver HARP tep{Smit2003} due for commissioning on the JCMT in 2004. The ROVER/HARP back-end will be a digital auto-correlation spectrometer, known as ACSIS, designed specifically for the demanding data volumes from the HARP array receiver. ACSIS is being developed by DRAO, Penticton and UKATC. This paper will describe the data reduction of ROVER polarimetry data both in real-time by ACSIS-DR, and through the ORAC-DR data reduction pipeline.

New NATO Members: Security Consumers or Producers?

DTIC Science & Technology

2009-04-01

political constraints.3 Dr. Jamie Shea Director of Policy Planning, NATO Burden-sharing can be defined as “the distribution of costs and risks among...certainly a “guns versus butter ” debate in the allocation of resources, the demand for military expenditures is more complex. Social welfare spending...Outputs. At the end of the day, political solidarity is more important than specific notions of equal numerical contributions.64 Dr. Jamie Shea Director

The clinical impact of the novel tumor marker DR-70 in unresectable gastric cancer patients.

PubMed

Hung, Yi-Ping; Chen, Ming-Huang; Lin, June-Seng; Hsiao, Chin-Fu; Shan, Yan-Shen; Chen, Yeu-Chin; Chen, Li-Tzong; Liu, Tsang-Wu; Li, Chung-Pin; Chao, Yee

2018-07-01

Gastric cancer tumor markers, such as carcinoembryonic antigen (CEA) and cancer antigen 19-9 (CA 19-9), have been applied in clinical practice to screen or monitor treatment responses. However, their sensitivity and specificity are unsatisfactory. Therefore, we assessed the novel tumor marker DR-70 and evaluated its performance in screening and response monitoring. The study included newly diagnosed patients with advanced gastric cancer from March 2012 to October 2015. We measured the DR-70, CEA, and CA 19-9 levels at the time of enrollment. The patients subsequently underwent chemotherapy. We followed-up the patients every 3 months; DR-70 levels and abdominal computed tomography scans were re-evaluated and repeated, respectively, at each follow-up. The correlation between treatment response and DR-70 level after chemotherapy was analyzed. The overall survival and progression-free survival rates were also evaluated. A total of 51 patients with gastric cancer were enrolled. Most (82.4%) had metastatic disease. At enrollment, the sensitivity of DR-70 in our study group was 78.4%, compared with 52.9% and 43.1% for CEA and CA 19-9, respectively. When we used the three tumor markers together, the sensitivity increased to 80.4%. We observed a correlation between treatment response and DR-70 level after chemotherapy. No difference in either overall survival or progression-free survival was observed between the DR-70 positive and negative groups. However, a trend toward poorer overall survival was observed for the high DR-70 group, although this was not statistically significant. DR-70 is a powerful tool not only for screening unresectable gastric cancer but also for treatment response evaluation. Copyright © 2018. Published by Elsevier Taiwan LLC.

Challenge Online Time Series Clustering For Demand Response A Theory to Break the ‘Curse of Dimensionality'

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

Pal, Ranjan; Chelmis, Charalampos; Aman, Saima

The advent of smart meters and advanced communication infrastructures catalyzes numerous smart grid applications such as dynamic demand response, and paves the way to solve challenging research problems in sustainable energy consumption. The space of solution possibilities are restricted primarily by the huge amount of generated data requiring considerable computational resources and efficient algorithms. To overcome this Big Data challenge, data clustering techniques have been proposed. Current approaches however do not scale in the face of the “increasing dimensionality” problem where a cluster point is represented by the entire customer consumption time series. To overcome this aspect we first rethinkmore » the way cluster points are created and designed, and then design an efficient online clustering technique for demand response (DR) in order to analyze high volume, high dimensional energy consumption time series data at scale, and on the fly. Our online algorithm is randomized in nature, and provides optimal performance guarantees in a computationally efficient manner. Unlike prior work we (i) study the consumption properties of the whole population simultaneously rather than developing individual models for each customer separately, claiming it to be a ‘killer’ approach that breaks the “curse of dimensionality” in online time series clustering, and (ii) provide tight performance guarantees in theory to validate our approach. Our insights are driven by the field of sociology, where collective behavior often emerges as the result of individual patterns and lifestyles.« less

Frequency Regulation Services from Connected Residential Devices: Short Paper

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

Baker, Kyri; Jin, Xin; Vaidhynathan, Deepthi

In this paper, we demonstrate the potential benefits that residential buildings can provide for frequency regulation services in the electric power grid. In a hardware-in-the- loop (HIL) implementation, simulated homes along with a physical laboratory home are coordinated via a grid aggregator, and it is shown that their aggregate response has the potential to follow the regulation signal on a timescale of seconds. Connected (communication-enabled), devices in the National Renewable Energy Laboratory's (NREL's) Energy Systems Integration Facility (ESIF) received demand response (DR) requests from a grid aggregator, and the devices responded accordingly to meet the signal while satisfying user comfortmore » bounds and physical hardware limitations. Future research will address the issues of cybersecurity threats, participation rates, and reducing equipment wear-and-tear while providing grid services.« less

Estimating irrigation water demand in the Moroccan Drâa Valley using contingent valuation.

PubMed

Storm, Hugo; Heckelei, Thomas; Heidecke, Claudia

2011-10-01

Irrigation water management is crucial for agricultural production and livelihood security in Morocco as in many other parts of the world. For the implementation of an effective water management, knowledge about farmers' demand for irrigation water is crucial to assess reactions to water pricing policy, to establish a cost-benefit analysis of water supply investments or to determine the optimal water allocation between different users. Previously used econometric methods providing this information often have prohibitive data requirements. In this paper, the Contingent Valuation Method (CVM) is adjusted to derive a demand function for irrigation water along farmers' willingness to pay for one additional unit of surface water or groundwater. An application in the Middle Drâa Valley in Morocco shows that the method provides reasonable results in an environment with limited data availability. For analysing the censored survey data, the Least Absolute Deviation estimator was found to be a more suitable alternative to the Tobit model as errors are heteroscedastic and non-normally distributed. The adjusted CVM to derive demand functions is especially attractive for water scarce countries under limited data availability. Copyright © 2011 Elsevier Ltd. All rights reserved.

Power management and frequency regulation for microgrid and smart grid: A real-time demand response approach

NASA Astrophysics Data System (ADS)

Pourmousavi Kani, Seyyed Ali

Future power systems (known as smart grid) will experience a high penetration level of variable distributed energy resources to bring abundant, affordable, clean, efficient, and reliable electric power to all consumers. However, it might suffer from the uncertain and variable nature of these generations in terms of reliability and especially providing required balancing reserves. In the current power system structure, balancing reserves (provided by spinning and non-spinning power generation units) usually are provided by conventional fossil-fueled power plants. However, such power plants are not the favorite option for the smart grid because of their low efficiency, high amount of emissions, and expensive capital investments on transmission and distribution facilities, to name a few. Providing regulation services in the presence of variable distributed energy resources would be even more difficult for islanded microgrids. The impact and effectiveness of demand response are still not clear at the distribution and transmission levels. In other words, there is no solid research reported in the literature on the evaluation of the impact of DR on power system dynamic performance. In order to address these issues, a real-time demand response approach along with real-time power management (specifically for microgrids) is proposed in this research. The real-time demand response solution is utilized at the transmission (through load-frequency control model) and distribution level (both in the islanded and grid-tied modes) to provide effective and fast regulation services for the stable operation of the power system. Then, multiple real-time power management algorithms for grid-tied and islanded microgrids are proposed to economically and effectively operate microgrids. Extensive dynamic modeling of generation, storage, and load as well as different controller design are considered and developed throughout this research to provide appropriate models and simulation environment to evaluate the effectiveness of the proposed methodologies. Simulation results revealed the effectiveness of the proposed methods in providing balancing reserves and microgrids' economic and stable operation. The proposed tools and approaches can significantly enhance the application of microgrids and demand response in the smart grid era. They will also help to increase the penetration level of variable distributed generation resources in the smart grid.

Customer response to day-ahead wholesale market electricity prices: Case study of RTP program experience in New York

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

Goldman, C.; Hopper, N.; Sezgen, O.

2004-07-01

There is growing interest in policies, programs and tariffs that encourage customer loads to provide demand response (DR) to help discipline wholesale electricity markets. Proposals at the retail level range from eliminating fixed rate tariffs as the default service for some or all customer groups to reinstituting utility-sponsored load management programs with market-based inducements to curtail. Alternative rate designs include time-of-use (TOU), day-ahead real-time pricing (RTP), critical peak pricing, and even pricing usage at real-time market balancing prices. Some Independent System Operators (ISOs) have implemented their own DR programs whereby load curtailment capabilities are treated as a system resource andmore » are paid an equivalent value. The resulting load reductions from these tariffs and programs provide a variety of benefits, including limiting the ability of suppliers to increase spot and long-term market-clearing prices above competitive levels (Neenan et al., 2002; Boren stein, 2002; Ruff, 2002). Unfortunately, there is little information in the public domain to characterize and quantify how customers actually respond to these alternative dynamic pricing schemes. A few empirical studies of large customer RTP response have shown modest results for most customers, with a few very price-responsive customers providing most of the aggregate response (Herriges et al., 1993; Schwarz et al., 2002). However, these studies examined response to voluntary, two-part RTP programs implemented by utilities in states without retail competition.1 Furthermore, the researchers had limited information on customer characteristics so they were unable to identify the drivers to price response. In the absence of a compelling characterization of why customers join RTP programs and how they respond to prices, many initiatives to modernize retail electricity rates seem to be stymied.« less

Intermittent Renewable Management Pilot Phase 2

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

Kiliccote, Sila; Homan, Gregory; Anderson, Robert

The Intermittent Renewable Management Pilot - Phase 2 (IRM2) was designed to study the feasibility of demand-side resources to participate into the California Independent System Operator (CAISO) wholesale market as proxy demand resources (PDR). The pilot study focused on understanding the issues related with direct participation of third-parties and customers including customer acceptance; market transformation challenges (wholesale market, technology); technical and operational feasibility; and value to the rate payers, DR resource owners and the utility on providing an enabling mechanism for DR resources into the wholesale markets. The customer had the option of committing to either three contiguous hour blocksmore » for 24 days or six contiguous hours for 12 days a month with day-ahead notification that aligned with the CAISO integrated forward market. As a result of their being available, the customer was paid $10/ kilowatt (kW)-month for capacity in addition to CAISO energy settlements. The participants were limited to no more than a 2 megawatt (MW) capacity with a six-month commitment. Four participants successfully engaged in the pilot. In this report, we provide the description of the pilot, participant performance results, costs and value to participants as well as outline some of the issues encountered through the pilot. Results show that participants chose to participate with storage and the value of CAISO settlements were significantly lower than the capacity payments provided by the utility as incentive payments. In addition, this pilot revealed issues both on the participant side and system operations side. These issues are summarized in the report.The Intermittent Renewable Management Pilot - Phase 2 (IRM2) was designed to study the feasibility of demand-side resources to participate into the California Independent System Operator (CAISO) wholesale market as proxy demand resources (PDR). The pilot study focused on understanding the issues related with direct participation of third-parties and customers including customer acceptance; market transformation challenges (wholesale market, technology); technical and operational feasibility; and value to the rate payers, DR resource owners and the utility on providing an enabling mechanism for DR resources into the wholesale markets.« less

Sex differences in body composition, fat storage, and gene expression profile in Caenorhabditis elegans in response to dietary restriction.

PubMed

Miersch, Claudia; Döring, Frank

2013-07-02

The metabolic and health-promoting effects of dietary restriction (DR) have been extensively studied in several species. The response to DR with respect to sex is essentially unknown. To address this question, we used the model organism Caenorhabditis elegans to analyze body composition and gene expression in males and hermaphrodites in response to DR. Unexpectedly, DR increased the fat-to-fat-free mass ratio and enlarged lipid droplets in both sexes to a similar extent. These effects were linked to a downregulation of the lipase-like 5 (lipl-5) gene in both sexes at two developmental stages. By contrast, the reductions in body size, protein content, and total RNA content in response to DR were more pronounced in hermaphrodites than in males. Functional enrichment analysis of gene expression data showed a DR-induced downregulation of several embryogenesis-associated genes concomitant with an ongoing expression of sperm-associated genes in hermaphrodites. In conclusion, DR increases fat stores in both sexes of C. elegans in the form of large and possibly lipolysis-resistant lipid droplets and markedly alters the reproductive program in hermaphrodites but not in males.

Japan, Indonesia to investigate condom plant feasibility.

PubMed

1981-04-01

The Japanese government has begun investigations on the possibility of constructing a condom manufacturing plant in Indonesia in response to a request by the Indonesian government. Indonesia, which hopes to reduce its birthrate as of 1971 by 1/2 by 1990, asked for Japanese assistance in building a condom plant based on the expectation that demand for this contraceptive method, although quite low at present, will increase rapidly in the near future with stepped-up motivation campaigns. As a 1st step in the investigation, the Japan International Cooperation Agency (JICA) sent a study team of family planning experts headed by Family Planning Federation of Japan Chairman Dr. Hidebumi Kubo and including JOICFP International Division Director MR. Tameyoshi Katagiri to Indonesia from March 15-24. During its visit, the JICA team held discussions with representatives of BKKBN (the National Family Planning Coordinating Board) including its Chairman and Minister of Health Dr. Suwardjono and reached agreement on the scope and schedule of work toward determining the feasibility of building and operating a condom plant in Indonesia. In defining the scope of work and the schedule, the JICA team and the BKKBN representatives decided on specific issues to be investigated in the feasibility study to be carried out by JICA and scheduled to be completed by the end of October of this year. To be included in the feasibility study are: estimation of future domestic demand for condoms, examination of the domestic supply of latex capacity, chemicals and packaging materials, and collection of information on infrastructure relating to water, energy, transportation, etc. Actual data collection for the study is expected to begin in late May or early June. Dr. Kubo and Mr. Katagiri, upon returning to Japan, reported great enthusiasm for the project in Indonesia and expressed the hope that the plant construction will be feasible so that the country's family planning program can be given a boost and the cooperative relationship between Indonesia and Japan deepened. full text

Change in Brooklyn and Queens: How New York?s Reforming the Energy Vision Program and Con Edison Are Reshaping Electric Distribution Planning

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

Coddington, Michael; Sciano, Damian; Fuller, Jason

In response to this tremendous growth in both population and electricity demand, Con Edison estimates that its cost to expand the “traditional” Brooklyn-Queens grid will be in the neighborhood of US$1.2 billion—a relatively high number, even for New York City and Con Edison. The complexity of the city’s underground electrical system along with the difficulties of construction in a highly congested urban environment with infrastructure both above and below ground mean that the costs for transmission, substations, and secondary networks are significantly higher than those of a typical electric utility. The New York State Public Service Commission (PSC) is inmore » the process revising its approach to acquiring and serving energy throughout the state of New York, and traditional expansion for this rather costly project was not likely to be approved. Instead, the PSC asked Con Edison to evaluate numerous alternatives. The PSC and Con Edison are now considering and adopting strategies that include renewable energy generation, demand response (DR), battery energy storage systems, fuel-cell distributed generation, combined heat and power, volt-volt ampere reactive (VAR) optimization (VVO), and a host of other innovative solutions that would both reduce electricity demand and transform how and when Con Edison’s consumers use electricity.« less

Evaluation of the DEIMS (Defense Economic Impact Modeling System) System.

DTIC Science & Technology

1984-07-01

AOORESS(H d~fereet m Caii~dl Offiee) IS. SECURITY CLASS. (of Wd e~w Vr OUSDRE (DoD-IDA Management Office) UCASFE 1801 N. Beauregard Street UCASFE...Defense Spending Mr. Paul Dickens, PA&E Labor Demand - Dr. David Blond Conclusion - Dr. David L. Mdicol 11:00 Break SESSION III - IMPACT OF DEFENSE...presented highlights of the industrial and labor impact of defense spending during. . 1985-89. Mr. Paul Dickens then analysed trends in the I- .""L- " ’•L

Diving Response in Rats: Role of the Subthalamic Vasodilator Area

PubMed Central

Golanov, Eugene V.; Shiflett, James M.; Britz, Gavin W.

2016-01-01

Diving response (DR) is a powerful integrative response targeted toward survival of the hypoxic/anoxic conditions. Being present in all animals and humans, it allows to survive adverse conditions like diving. Earlier, we discovered that forehead stimulation affords neuroprotective effect, decreasing infarction volume triggered by permanent occlusion of the middle cerebral artery in rats. We hypothesized that cold stimulation of the forehead induces DR in rats, which, in turn, exerts neuroprotection. We compared autonomic [AP, heart rate (HR), cerebral blood flow (CBF)] and EEG responses to the known DR-triggering stimulus, ammonia stimulation of the nasal mucosa, cold stimulation of the forehead, and cold stimulation of the glabrous skin of the tail base in anesthetized rats. Responses in AP, HR, CBF, and EEG to cold stimulation of the forehead and ammonia vapors instillation into the nasal cavity were comparable and differed significantly from responses to the cold stimulation of the tail base. Excitotoxic lesion of the subthalamic vasodilator area (SVA), which is known to participate in CBF regulation and to afford neuroprotection upon excitation, failed to affect autonomic components of the DR evoked by forehead cold stimulation or nasal mucosa ammonia stimulation. We conclude that cold stimulation of the forehead triggers physiological response comparable to the response evoked by ammonia vapor instillation into nasal cavity, which is considered as stimulus triggering protective DR. These observations may explain the neuroprotective effect of the forehead stimulation. Data demonstrate that SVA does not directly participate in the autonomic adjustments accompanying DR; however, it is involved in diving-evoked modulation of EEG. We suggest that forehead stimulation can be employed as a stimulus capable of triggering oxygen-conserving DR and can be used for neuroprotective therapy. PMID:27708614

Short Paper: Frequency Regulation Services from Connected Residential Devices: Preprint

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

Baker, Kyri; Jin, Xin; Vaidhynathan, Deepthi

In this paper, we demonstrate the potential benefits that residential buildings can provide for frequency regulation services in the electric power grid. In a hardware-in-the- loop (HIL) implementation, simulated homes along with a physical laboratory home are coordinated via a grid aggregator, and it is shown that their aggregate response has the potential to follow the regulation signal on a timescale of seconds. Connected (communication-enabled), devices in the National Renewable Energy Laboratory's (NREL's) Energy Systems Integration Facility (ESIF) received demand response (DR) requests from a grid aggregator, and the devices responded accordingly to meet the signal while satisfying user comfortmore » bounds and physical hardware limitations. Future research will address the issues of cybersecurity threats, participation rates, and reducing equipment wear-and-tear while providing grid services.« less

Component-Based Modelling for Scalable Smart City Systems Interoperability: A Case Study on Integrating Energy Demand Response Systems.

PubMed

Palomar, Esther; Chen, Xiaohong; Liu, Zhiming; Maharjan, Sabita; Bowen, Jonathan

2016-10-28

Smart city systems embrace major challenges associated with climate change, energy efficiency, mobility and future services by embedding the virtual space into a complex cyber-physical system. Those systems are constantly evolving and scaling up, involving a wide range of integration among users, devices, utilities, public services and also policies. Modelling such complex dynamic systems' architectures has always been essential for the development and application of techniques/tools to support design and deployment of integration of new components, as well as for the analysis, verification, simulation and testing to ensure trustworthiness. This article reports on the definition and implementation of a scalable component-based architecture that supports a cooperative energy demand response (DR) system coordinating energy usage between neighbouring households. The proposed architecture, called refinement of Cyber-Physical Component Systems (rCPCS), which extends the refinement calculus for component and object system (rCOS) modelling method, is implemented using Eclipse Extensible Coordination Tools (ECT), i.e., Reo coordination language. With rCPCS implementation in Reo, we specify the communication, synchronisation and co-operation amongst the heterogeneous components of the system assuring, by design scalability and the interoperability, correctness of component cooperation.

Component-Based Modelling for Scalable Smart City Systems Interoperability: A Case Study on Integrating Energy Demand Response Systems

PubMed Central

Palomar, Esther; Chen, Xiaohong; Liu, Zhiming; Maharjan, Sabita; Bowen, Jonathan

2016-01-01

Smart city systems embrace major challenges associated with climate change, energy efficiency, mobility and future services by embedding the virtual space into a complex cyber-physical system. Those systems are constantly evolving and scaling up, involving a wide range of integration among users, devices, utilities, public services and also policies. Modelling such complex dynamic systems’ architectures has always been essential for the development and application of techniques/tools to support design and deployment of integration of new components, as well as for the analysis, verification, simulation and testing to ensure trustworthiness. This article reports on the definition and implementation of a scalable component-based architecture that supports a cooperative energy demand response (DR) system coordinating energy usage between neighbouring households. The proposed architecture, called refinement of Cyber-Physical Component Systems (rCPCS), which extends the refinement calculus for component and object system (rCOS) modelling method, is implemented using Eclipse Extensible Coordination Tools (ECT), i.e., Reo coordination language. With rCPCS implementation in Reo, we specify the communication, synchronisation and co-operation amongst the heterogeneous components of the system assuring, by design scalability and the interoperability, correctness of component cooperation. PMID:27801829

HLA-DR4-associated T and B cell responses to specific determinants on the IA-2 autoantigen in type 1 diabetes.

PubMed

McLaughlin, Kerry A; Gulati, Kavita; Richardson, Carolyn C; Morgan, Diana; Bodansky, H Jonathan; Feltbower, Richard G; Christie, Michael R

2014-11-01

Autoantibodies to IA-2 in type 1 diabetes are associated with HLA-DR4, suggesting influences of HLA-DR4-restricted T cells on IA-2-specific B cell responses. The aim of this study was to investigate possible T-B cell collaboration by determining whether autoantibodies to IA-2 epitopes are associated with T cell responses to IA-2 peptides presented by DR4. T cells secreting the cytokines IFN-γ and IL-10 in response to seven peptides known to elicit T cell responses in type 1 diabetes were quantified by cytokine ELISPOT in HLA-typed patients characterized for Abs to IA-2 epitopes. T cell responses were detected to all peptides tested, but only IL-10 responses to 841-860 and 853-872 peptides were associated with DR4. Phenotyping by RT-PCR of FACS-sorted CD45RO(hi) T cells secreting IL-10 in response to these two peptides indicated that these expressed GATA-3 or T-bet, but not FOXP3, consistent with these being Th2 or Th1 memory T cells rather than of regulatory phenotype. T cell responses to the same two peptides were also associated with specific Abs: those to 841-860 peptide with Abs to juxtamembrane epitopes, which appear early in prediabetes, and those to peptide 853-872 with Abs to an epitope located in the 831-862 central region of the IA-2 tyrosine phosphatase domain. Abs to juxtamembrane and central region constructs were both DR4 associated. This study identifies a region of focus for B and T cell responses to IA-2 in HLA-DR4 diabetic patients that may explain HLA associations of IA-2 autoantibodies, and this region may provide a target for future immune intervention to prevent disease. Copyright © 2014 by The American Association of Immunologists, Inc.

Peptide immunisation of HLA-DR-transgenic mice permits the identification of a novel HLA-DRbeta1*0101- and HLA-DRbeta1*0401-restricted epitope from p53.

PubMed

Rojas, José Manuel; McArdle, Stephanie E B; Horton, Roger B V; Bell, Matthew; Mian, Shahid; Li, Geng; Ali, Selman A; Rees, Robert C

2005-03-01

Because of the central role of CD4(+) T cells in antitumour immunity, the identification of the MHC class II-restricted peptides to which CD4(+) T cells respond has become a priority of tumour immunologists. Here, we describe a strategy permitting us to rapidly determine the immunogenicity of candidate HLA-DR-restricted peptides using peptide immunisation of HLA-DR-transgenic mice, followed by assessment of the response in vitro. This strategy was successfully applied to the reported haemaglutinin influenza peptide HA(307-319), and then extended to three candidate HLA-DR-restricted p53 peptides predicted by the evidence-based algorithm SYFPEITHI to bind to HLA-DRbeta1*0101 (HLA-DR1) and HLA-DRbeta1*0401 (HLA-DR4) molecules. One of these peptides, p53(108-122), consistently induced responses in HLA-DR1- and in HLA-DR4-transgenic mice. Moreover, this peptide was naturally processed by dendritic cells (DCs), and induced specific proliferation in the splenocytes of mice immunised with p53 cDNA, demonstrating that immune responses could be naturally mounted to the peptide. Furthermore, p53(108-122) peptide was also immunogenic in HLA-DR1 and HLA-DR4 healthy donors. Thus, the use of this transgenic model permitted the identification of a novel HLA-DR-restricted epitope from p53 and constitutes an attractive approach for the rapid identification of novel immunogenic MHC class II-restricted peptides from tumour antigens, which can ultimately be incorporated in immunotherapeutic protocols.

Pathogenesis of human diffusely adhering Escherichia coli expressing Afa/Dr adhesins (Afa/Dr DAEC): current insights and future challenges.

PubMed

Servin, Alain L

2014-10-01

The pathogenicity and clinical pertinence of diffusely adhering Escherichia coli expressing the Afa/Dr adhesins (Afa/Dr DAEC) in urinary tract infections (UTIs) and pregnancy complications are well established. In contrast, the implication of intestinal Afa/Dr DAEC in diarrhea is still under debate. These strains are age dependently involved in diarrhea in children, are apparently not involved in diarrhea in adults, and can also be asymptomatic intestinal microbiota strains in children and adult. This comprehensive review analyzes the epidemiology and diagnosis and highlights recent progress which has improved the understanding of Afa/Dr DAEC pathogenesis. Here, I summarize the roles of Afa/Dr DAEC virulence factors, including Afa/Dr adhesins, flagella, Sat toxin, and pks island products, in the development of specific mechanisms of pathogenicity. In intestinal epithelial polarized cells, the Afa/Dr adhesins trigger cell membrane receptor clustering and activation of the linked cell signaling pathways, promote structural and functional cell lesions and injuries in intestinal barrier, induce proinflammatory responses, create angiogenesis, instigate epithelial-mesenchymal transition-like events, and lead to pks-dependent DNA damage. UTI-associated Afa/Dr DAEC strains, following adhesin-membrane receptor cell interactions and activation of associated lipid raft-dependent cell signaling pathways, internalize in a microtubule-dependent manner within urinary tract epithelial cells, develop a particular intracellular lifestyle, and trigger a toxin-dependent cell detachment. In response to Afa/Dr DAEC infection, the host epithelial cells generate antibacterial defense responses. Finally, I discuss a hypothetical role of intestinal Afa/Dr DAEC strains that can act as "silent pathogens" with the capacity to emerge as "pathobionts" for the development of inflammatory bowel disease and intestinal carcinogenesis. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Pathogenesis of Human Diffusely Adhering Escherichia coli Expressing Afa/Dr Adhesins (Afa/Dr DAEC): Current Insights and Future Challenges

PubMed Central

2014-01-01

SUMMARY The pathogenicity and clinical pertinence of diffusely adhering Escherichia coli expressing the Afa/Dr adhesins (Afa/Dr DAEC) in urinary tract infections (UTIs) and pregnancy complications are well established. In contrast, the implication of intestinal Afa/Dr DAEC in diarrhea is still under debate. These strains are age dependently involved in diarrhea in children, are apparently not involved in diarrhea in adults, and can also be asymptomatic intestinal microbiota strains in children and adult. This comprehensive review analyzes the epidemiology and diagnosis and highlights recent progress which has improved the understanding of Afa/Dr DAEC pathogenesis. Here, I summarize the roles of Afa/Dr DAEC virulence factors, including Afa/Dr adhesins, flagella, Sat toxin, and pks island products, in the development of specific mechanisms of pathogenicity. In intestinal epithelial polarized cells, the Afa/Dr adhesins trigger cell membrane receptor clustering and activation of the linked cell signaling pathways, promote structural and functional cell lesions and injuries in intestinal barrier, induce proinflammatory responses, create angiogenesis, instigate epithelial-mesenchymal transition-like events, and lead to pks-dependent DNA damage. UTI-associated Afa/Dr DAEC strains, following adhesin-membrane receptor cell interactions and activation of associated lipid raft-dependent cell signaling pathways, internalize in a microtubule-dependent manner within urinary tract epithelial cells, develop a particular intracellular lifestyle, and trigger a toxin-dependent cell detachment. In response to Afa/Dr DAEC infection, the host epithelial cells generate antibacterial defense responses. Finally, I discuss a hypothetical role of intestinal Afa/Dr DAEC strains that can act as “silent pathogens” with the capacity to emerge as “pathobionts” for the development of inflammatory bowel disease and intestinal carcinogenesis. PMID:25278576

NLRP1 deficiency attenuates diabetic retinopathy (DR) in mice through suppressing inflammation response.

PubMed

Li, Yan; Liu, Chang; Wan, Xin-Shun; Li, Shao-Wei

2018-06-22

Diabetic retinopathy (DR) is the common cause of diabetic vascular complications. The NOD-like receptor (NLR) family, pyrin domain containing 1 (NLRP1), also known as NALP1, inflammasome is the first member of the NLR family to be discovered, playing an important role in inflammatory response. However, its effect on DR development has not been reported. In the study, the wild type (WT) and NLRP1 -/- mice were injected with streptozotocin (STZ) to induce DR. The results indicated that NLRP1 -/- significantly increased bodyweight reduction and decreased blood glucose levels induced by STZ. WT/DR mice exhibited higher levels of NLRP1 in retinas. NLRP1 -/- ameliorated retinal abnormalities in DR mice using H&E staining. In addition, attenuated avascular areas and neovascular tufts were also observed in NLRP1 -/- /DR mice. The levels of pro-inflammatory cytokines in serum and retinas were highly induced in WT/DR mice, whereas being markedly reduced by NLRP1 -/- . In addition, vascular endothelial growth factor (VEGF) and Iba1 expressions induced by STZ in serum or retinas were significantly down-regulated in NLRP1 -/- /DR mice. Consistently, NLRP1 -/- attenuated ASC and Caspase-1 expressions in retinas of DR mice. Compared to WT/DR group, NLRP1 -/- markedly decreased retina p-nuclear factor-κB (NF-κB), interleukin-1β (IL-1β) and IL-18 levels. And similar results were confirmed in vitro that suppressing NLRP1/ASC inflammasome ameliorated inflammatory response in fructose-treated retinal ganglion cells. The results above indicated that the modulation of NLRP1 inflammasome might be a promising strategy for DR therapy. Copyright © 2018. Published by Elsevier Inc.

Gene Expression Ratios Lead to Accurate and Translatable Predictors of DR5 Agonism across Multiple Tumor Lineages.

PubMed

Reddy, Anupama; Growney, Joseph D; Wilson, Nick S; Emery, Caroline M; Johnson, Jennifer A; Ward, Rebecca; Monaco, Kelli A; Korn, Joshua; Monahan, John E; Stump, Mark D; Mapa, Felipa A; Wilson, Christopher J; Steiger, Janine; Ledell, Jebediah; Rickles, Richard J; Myer, Vic E; Ettenberg, Seth A; Schlegel, Robert; Sellers, William R; Huet, Heather A; Lehár, Joseph

2015-01-01

Death Receptor 5 (DR5) agonists demonstrate anti-tumor activity in preclinical models but have yet to demonstrate robust clinical responses. A key limitation may be the lack of patient selection strategies to identify those most likely to respond to treatment. To overcome this limitation, we screened a DR5 agonist Nanobody across >600 cell lines representing 21 tumor lineages and assessed molecular features associated with response. High expression of DR5 and Casp8 were significantly associated with sensitivity, but their expression thresholds were difficult to translate due to low dynamic ranges. To address the translational challenge of establishing thresholds of gene expression, we developed a classifier based on ratios of genes that predicted response across lineages. The ratio classifier outperformed the DR5+Casp8 classifier, as well as standard approaches for feature selection and classification using genes, instead of ratios. This classifier was independently validated using 11 primary patient-derived pancreatic xenograft models showing perfect predictions as well as a striking linearity between prediction probability and anti-tumor response. A network analysis of the genes in the ratio classifier captured important biological relationships mediating drug response, specifically identifying key positive and negative regulators of DR5 mediated apoptosis, including DR5, CASP8, BID, cFLIP, XIAP and PEA15. Importantly, the ratio classifier shows translatability across gene expression platforms (from Affymetrix microarrays to RNA-seq) and across model systems (in vitro to in vivo). Our approach of using gene expression ratios presents a robust and novel method for constructing translatable biomarkers of compound response, which can also probe the underlying biology of treatment response.

Gene Expression Ratios Lead to Accurate and Translatable Predictors of DR5 Agonism across Multiple Tumor Lineages

PubMed Central

Reddy, Anupama; Growney, Joseph D.; Wilson, Nick S.; Emery, Caroline M.; Johnson, Jennifer A.; Ward, Rebecca; Monaco, Kelli A.; Korn, Joshua; Monahan, John E.; Stump, Mark D.; Mapa, Felipa A.; Wilson, Christopher J.; Steiger, Janine; Ledell, Jebediah; Rickles, Richard J.; Myer, Vic E.; Ettenberg, Seth A.; Schlegel, Robert; Sellers, William R.

2015-01-01

Death Receptor 5 (DR5) agonists demonstrate anti-tumor activity in preclinical models but have yet to demonstrate robust clinical responses. A key limitation may be the lack of patient selection strategies to identify those most likely to respond to treatment. To overcome this limitation, we screened a DR5 agonist Nanobody across >600 cell lines representing 21 tumor lineages and assessed molecular features associated with response. High expression of DR5 and Casp8 were significantly associated with sensitivity, but their expression thresholds were difficult to translate due to low dynamic ranges. To address the translational challenge of establishing thresholds of gene expression, we developed a classifier based on ratios of genes that predicted response across lineages. The ratio classifier outperformed the DR5+Casp8 classifier, as well as standard approaches for feature selection and classification using genes, instead of ratios. This classifier was independently validated using 11 primary patient-derived pancreatic xenograft models showing perfect predictions as well as a striking linearity between prediction probability and anti-tumor response. A network analysis of the genes in the ratio classifier captured important biological relationships mediating drug response, specifically identifying key positive and negative regulators of DR5 mediated apoptosis, including DR5, CASP8, BID, cFLIP, XIAP and PEA15. Importantly, the ratio classifier shows translatability across gene expression platforms (from Affymetrix microarrays to RNA-seq) and across model systems (in vitro to in vivo). Our approach of using gene expression ratios presents a robust and novel method for constructing translatable biomarkers of compound response, which can also probe the underlying biology of treatment response. PMID:26378449

A Proteome Translocation Response to Complex Desert Stress Environments in Perennial Phragmites Sympatric Ecotypes with Contrasting Water Availability.

PubMed

Li, Li; Chen, Xiaodan; Shi, Lu; Wang, Chuanjing; Fu, Bing; Qiu, Tianhang; Cui, Suxia

2017-01-01

After a long-term adaptation to desert environment, the perennial aquatic plant Phragmites communis has evolved a desert-dune ecotype. The desert-dune ecotype (DR) of Phragmites communis showed significant differences in water activity and protein distribution compared to its sympatric swamp ecotype (SR). Many proteins that were located in the soluble fraction of SR translocated to the insoluble fraction of DR, suggesting that membrane-associated proteins were greatly reinforced in DR. The unknown phenomenon in plant stress physiology was defined as a proteome translocation response. Quantitative 2D-DIGE technology highlighted these 'bound' proteins in DR. Fifty-eight kinds of proteins were identified as candidates of the translocated proteome in Phragmites . The majority were chloroplast proteins. Unexpectedly, Rubisco was the most abundant protein sequestered by DR. Rubisco activase, various chaperons and 2-cysteine peroxiredoxin were major components in the translocation response. Conformational change was assumed to be the main reason for the Rubisco translocation due to no primary sequence difference between DR and SR. The addition of reductant in extraction process partially reversed the translocation response, implying that intracellular redox status plays a role in the translocation response of the proteome. The finding emphasizes the realistic significance of the membrane-association of biomolecule for plant long-term adaptation to complex stress conditions.

Technical and Economic Aspects of Designing an Efficient Room Air-Conditioner Program in India

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

Abhyankar, Nikit; Shah, Nihar; Phadke, Amol

Several studies have projected a massive increase in the demand for air conditioners (ACs) over the next two decades in India. By 2030, room ACs could add 140 GW to the peak load, equivalent to over 30% of the total projected peak load. Therefore, there is significant interest among policymakers, regulators, and utilities in managing room AC demand by enhancing energy efficiency. Building on the historical success of the Indian Bureau of Energy Efficiency’s star-labeling program, Energy Efficiency Services Limited recently announced a program to accelerate the sale of efficient room ACs using bulk procurement, similar to their successful UJALAmore » light-emitting diode (LED) bulk procurement program. This report discusses some of the key considerations in designing a bulk procurement or financial incentive program for enhancing room AC efficiency in India. We draw upon our previous research to demonstrate the overall technical potential and price impact of room AC efficiency improvement and its technical feasibility in India. We also discuss the importance of using low global warming potential (GWP) refrigerants and smart AC equipment that is demand response (DR) ready.« less

The worldwide epidemic of diabetic retinopathy

PubMed Central

Zheng, Yingfeng; He, Mingguang; Congdon, Nathan

2012-01-01

Diabetic retinopathy (DR), a major microvascular complication of diabetes, has a significant impact on the world's health systems. Globally, the number of people with DR will grow from 126.6 million in 2010 to 191.0 million by 2030, and we estimate that the number with vision-threatening diabetic retinopathy (VTDR) will increase from 37.3 million to 56.3 million, if prompt action is not taken. Despite growing evidence documenting the effectiveness of routine DR screening and early treatment, DR frequently leads to poor visual functioning and represents the leading cause of blindness in working-age populations. DR has been neglected in health-care research and planning in many low-income countries, where access to trained eye-care professionals and tertiary eye-care services may be inadequate. Demand for, as well as, supply of services may be a problem. Rates of compliance with diabetes medications and annual eye examinations may be low, the reasons for which are multifactorial. Innovative and comprehensive approaches are needed to reduce the risk of vision loss by prompt diagnosis and early treatment of VTDR. PMID:22944754

The worldwide epidemic of diabetic retinopathy.

PubMed

Zheng, Yingfeng; He, Mingguang; Congdon, Nathan

2012-01-01

Diabetic retinopathy (DR), a major microvascular complication of diabetes, has a significant impact on the world's health systems. Globally, the number of people with DR will grow from 126.6 million in 2010 to 191.0 million by 2030, and we estimate that the number with vision-threatening diabetic retinopathy (VTDR) will increase from 37.3 million to 56.3 million, if prompt action is not taken. Despite growing evidence documenting the effectiveness of routine DR screening and early treatment, DR frequently leads to poor visual functioning and represents the leading cause of blindness in working-age populations. DR has been neglected in health-care research and planning in many low-income countries, where access to trained eye-care professionals and tertiary eye-care services may be inadequate. Demand for, as well as, supply of services may be a problem. Rates of compliance with diabetes medications and annual eye examinations may be low, the reasons for which are multifactorial. Innovative and comprehensive approaches are needed to reduce the risk of vision loss by prompt diagnosis and early treatment of VTDR.

Parenting During Residency: Providing Support for Dr Mom and Dr Dad.

PubMed

Morris, Laura; Cronk, Nikole J; Washington, Karla T

2016-02-01

Parenting during family medicine residency is increasingly common. Relatively little is known about how the competing demands of work and family life affect residents. We conducted an exploratory qualitative study of parenting family medicine residents at one program in the Midwest utilizing focus groups to understand residents' perceptions of the positive and negative characteristics of their roles as physicians and parents. We used consensus coding to identify themes in the data and then developed a model to illustrate the relationships among the identified themes. Competing demands on their time require parenting family medicine residents to often make difficult choices, which result in both positive and negative outcomes for residents, their families, and their residency experience. Parenting family medicine residents experience numerous conflicts in their concurrent roles of learner, physician, and parent. Parenting-friendly residency training programs would likely offer valuable support for these individuals during this stressful life period.

Modulation of microglia in the retina: new insights into diabetic retinopathy.

PubMed

Arroba, Ana I; Valverde, Ángela M

2017-06-01

During last decades, the diagnosis of diabetes has been associated with several chronic complications such as diabetic retinopathy (DR). Recent studies of DR have revealed an inflammatory component, which precedes the detection of alterations in the visual function. During DR, the inflammatory process presents two opposite roles depending on the polarization of resident immune cells of the retina triggering proinflammatory (M1) or antiinflammatory (M2) actions. In an early stage of DR, the M2 response concurs with the M1 and is able to ameliorate inflammation and delay the progression of the disease. However, during the progression of DR, the M1 response is maintained whereas the M2 declines and, in this scenario, the classical proinflammatory signaling pathways are chronically activated leading to retinal neurodegeneration and the loss of visual function. The M1/M2 responses are closely related to the activation and polarization of microglial cells. This review aims to offer an overview of the recent insights into the role of microglial cells during inflammation in DR. We have focused on the possibility of modulating microglia polarization as a new therapeutic strategy in DR treatments.

Differential Response: What to Make of the Existing Research? A Response to Hughes et al.

ERIC Educational Resources Information Center

Drake, Brett

2013-01-01

This article is a response to "Issues in Differential Response", a review of the current evidence pertaining to differential response (DR) programs in child protective services (CPS). In my view, the Hughes, Rycus, Saunders-Adams, Hughes, and Hughes article suffers from several weaknesses. First, DR programs are critiqued as if they were…

A Proteome Translocation Response to Complex Desert Stress Environments in Perennial Phragmites Sympatric Ecotypes with Contrasting Water Availability

PubMed Central

Li, Li; Chen, Xiaodan; Shi, Lu; Wang, Chuanjing; Fu, Bing; Qiu, Tianhang; Cui, Suxia

2017-01-01

After a long-term adaptation to desert environment, the perennial aquatic plant Phragmites communis has evolved a desert-dune ecotype. The desert-dune ecotype (DR) of Phragmites communis showed significant differences in water activity and protein distribution compared to its sympatric swamp ecotype (SR). Many proteins that were located in the soluble fraction of SR translocated to the insoluble fraction of DR, suggesting that membrane-associated proteins were greatly reinforced in DR. The unknown phenomenon in plant stress physiology was defined as a proteome translocation response. Quantitative 2D-DIGE technology highlighted these ‘bound’ proteins in DR. Fifty-eight kinds of proteins were identified as candidates of the translocated proteome in Phragmites. The majority were chloroplast proteins. Unexpectedly, Rubisco was the most abundant protein sequestered by DR. Rubisco activase, various chaperons and 2-cysteine peroxiredoxin were major components in the translocation response. Conformational change was assumed to be the main reason for the Rubisco translocation due to no primary sequence difference between DR and SR. The addition of reductant in extraction process partially reversed the translocation response, implying that intracellular redox status plays a role in the translocation response of the proteome. The finding emphasizes the realistic significance of the membrane-association of biomolecule for plant long-term adaptation to complex stress conditions. PMID:28450873

The Changing Pattern of Doctoral Education in Public Health From 1985 to 2006 and the Challenge of Doctoral Training for Practice and Leadership

PubMed Central

Declercq, Eugene; Caldwell, Karen; Hobbs, Suzanne Havala; Guyer, Bernard

2008-01-01

We examined trends in doctoral education in public health and the challenges facing practice-oriented doctor of public health (DrPH) programs. We found a rapid rise in the numbers of doctoral programs and students. Most of the increase was in PhD students who in 2006 composed 73% of the total 5247 current public health doctoral students, compared with 53% in 1985. There has also been a substantial increase (40%) in students in DrPH programs since 2002. Challenges raised by the increased demand for DrPH practice-oriented education relate to admissions, curriculum, assessment processes, and faculty hiring and promotion. We describe approaches to practice-based doctoral education taken by three schools of public health. PMID:18633094

Topologically heterogeneous beta cell adaptation in response to high-fat diet in mice.

PubMed

Ellenbroek, Johanne H; Töns, Hendrica A; de Graaf, Natascha; Loomans, Cindy J; Engelse, Marten A; Vrolijk, Hans; Voshol, Peter J; Rabelink, Ton J; Carlotti, Françoise; de Koning, Eelco J

2013-01-01

Beta cells adapt to an increased insulin demand by enhancing insulin secretion via increased beta cell function and/or increased beta cell number. While morphological and functional heterogeneity between individual islets exists, it is unknown whether regional differences in beta cell adaptation occur. Therefore we investigated beta cell adaptation throughout the pancreas in a model of high-fat diet (HFD)-induced insulin resistance in mice. C57BL/6J mice were fed a HFD to induce insulin resistance, or control diet for 6 weeks. The pancreas was divided in a duodenal (DR), gastric (GR) and splenic (SR) region and taken for either histology or islet isolation. The capacity of untreated islets from the three regions to adapt in an extrapancreatic location was assessed by transplantation under the kidney capsule of streptozotocin-treated mice. SR islets showed 70% increased beta cell proliferation after HFD, whereas no significant increase was found in DR and GR islets. Furthermore, isolated SR islets showed twofold enhanced glucose-induced insulin secretion after HFD, as compared with DR and GR islets. In contrast, transplantation of islets isolated from the three regions to an extrapancreatic location in diabetic mice led to a similar decrease in hyperglycemia and no difference in beta cell proliferation. HFD-induced insulin resistance leads to topologically heterogeneous beta cell adaptation and is most prominent in the splenic region of the pancreas. This topological heterogeneity in beta cell adaptation appears to result from extrinsic factors present in the islet microenvironment.

Neurovascular cross talk in diabetic retinopathy: Pathophysiological roles and therapeutic implications

PubMed Central

Moran, Elizabeth P.; Wang, Zhongxiao; Chen, Jing; Sapieha, Przemyslaw; Smith, Lois E. H.

2016-01-01

Diabetic retinopathy (DR) is the leading cause of blindness in the working-age population in developed countries, and its prevalence will increase as the global incidence of diabetes grows exponentially. DR begins with an early nonproliferative stage in which retinal blood vessels and neurons degenerate as a consequence of chronic hyperglycemia, resulting in vasoregression and persistent retinal ischemia, metabolic disequilibrium, and inflammation. This is conducive to overcompensatory pathological neovascularization associated with advanced proliferative DR. Although DR is considered a microvascular complication, the retinal microvasculature is intimately associated with and governed by neurons and glia; neurodegeneration, neuroinflammation, and dysregulation of neurovascular cross talk are responsible in part for vascular abnormalities in both early nonproliferative DR and advanced proliferative DR. Neuronal activity directly regulates microvascular dilation and blood flow in the process of neurovascular coupling. Retinal neurons also secrete guidance cues in response to injury, ischemia, or metabolic stress that may either promote or suppress vascular outgrowth, either alleviating or exacerbating DR, contingent on the stage of disease and retinal microenvironment. Neurodegeneration, impaired neurovascular coupling, and dysregulation of neuronal guidance cues are key events in the pathogenesis of DR, and correcting these events may prevent or delay development of advanced DR. The review discusses the mechanisms of neurovascular cross talk and its dysregulation in DR, and their potential therapeutic implications. PMID:27473938

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

Cappers, Peter; MacDonald, Jason; Goldman, Charles

This study provides an examination of various market and policy barriers to demand response providing ancillary services in both ISO/RTO and non-ISO/RTO regions, especially at the program provider level. It is useful to classify barriers in order to create a holistic understanding and identify parties that could be responsible for their removal. This study develops a typology of barriers focusing on smaller customers that must rely on a program provider (i.e., electric investor owned utility or IOU, ARC) to create an aggregated DR resource in order to bring ancillary services to the balancing authority. The barriers were identified through examinationsmore » of regulatory structures, market environments, and product offerings; and discussions with industry stakeholders and regulators. In order to help illustrate the differences in barriers among various wholesale market designs and their constituent retail environments, four regions were chosen to use as case studies: Colorado, Texas, Wisconsin, and New Jersey.« less

Sharon Savage Appointed DCEG Clinical Director

Cancer.gov

Dr. Sharon Savage has been named as the new Clinical Director for DCEG, responsible for patient safety, research integrity, and responsible stewardship of research funding for all DCEG clinical activities. Learn more about Dr. Savage’s appointment

Retinal Imaging Techniques for Diabetic Retinopathy Screening

PubMed Central

Goh, James Kang Hao; Cheung, Carol Y.; Sim, Shaun Sebastian; Tan, Pok Chien; Tan, Gavin Siew Wei; Wong, Tien Yin

2016-01-01

Due to the increasing prevalence of diabetes mellitus, demand for diabetic retinopathy (DR) screening platforms is steeply increasing. Early detection and treatment of DR are key public health interventions that can greatly reduce the likelihood of vision loss. Current DR screening programs typically employ retinal fundus photography, which relies on skilled readers for manual DR assessment. However, this is labor-intensive and suffers from inconsistency across sites. Hence, there has been a recent proliferation of automated retinal image analysis software that may potentially alleviate this burden cost-effectively. Furthermore, current screening programs based on 2-dimensional fundus photography do not effectively screen for diabetic macular edema (DME). Optical coherence tomography is becoming increasingly recognized as the reference standard for DME assessment and can potentially provide a cost-effective solution for improving DME detection in large-scale DR screening programs. Current screening techniques are also unable to image the peripheral retina and require pharmacological pupil dilation; ultra-widefield imaging and confocal scanning laser ophthalmoscopy, which address these drawbacks, possess great potential. In this review, we summarize the current DR screening methods using various retinal imaging techniques, and also outline future possibilities. Advances in retinal imaging techniques can potentially transform the management of patients with diabetes, providing savings in health care costs and resources. PMID:26830491

Retinal Imaging Techniques for Diabetic Retinopathy Screening.

PubMed

Goh, James Kang Hao; Cheung, Carol Y; Sim, Shaun Sebastian; Tan, Pok Chien; Tan, Gavin Siew Wei; Wong, Tien Yin

2016-02-01

Due to the increasing prevalence of diabetes mellitus, demand for diabetic retinopathy (DR) screening platforms is steeply increasing. Early detection and treatment of DR are key public health interventions that can greatly reduce the likelihood of vision loss. Current DR screening programs typically employ retinal fundus photography, which relies on skilled readers for manual DR assessment. However, this is labor-intensive and suffers from inconsistency across sites. Hence, there has been a recent proliferation of automated retinal image analysis software that may potentially alleviate this burden cost-effectively. Furthermore, current screening programs based on 2-dimensional fundus photography do not effectively screen for diabetic macular edema (DME). Optical coherence tomography is becoming increasingly recognized as the reference standard for DME assessment and can potentially provide a cost-effective solution for improving DME detection in large-scale DR screening programs. Current screening techniques are also unable to image the peripheral retina and require pharmacological pupil dilation; ultra-widefield imaging and confocal scanning laser ophthalmoscopy, which address these drawbacks, possess great potential. In this review, we summarize the current DR screening methods using various retinal imaging techniques, and also outline future possibilities. Advances in retinal imaging techniques can potentially transform the management of patients with diabetes, providing savings in health care costs and resources. © 2016 Diabetes Technology Society.

Psychometric Approach to Error Analysis on Response Patterns of Achievement Tests.

DTIC Science & Technology

1980-02-01

Maxwell Dr. Richard L. Ferguson I Dr. Earl Hunt Department of Psychology The American Collage Testing Program Dept. of Psychology University of Houston...South Carolina Educational Testing Service Columbia. SC 29208 Princeton. NJ 08541 PROF. FiFIIKO SAMEJIMA 1 Dr. Kikumi Tatsuoka DEPT. OF PSYCHOLOGY ...Illinois Urbana Illinois PSYCHOMETRIC APPROACH TO ERROR ANALYSIS ON RESPONSE PATTERNS OF ACHIEVEMENT TESTS -.C, 0 ~KIKUMI K. TATSUOKA -’- MENUCHA

Oral administration of non-absorbable delayed release 6-mercaptopurine is locally active in the gut, exerts a systemic immune effect and alleviates Crohn’s disease with low rate of side effects: results of double blind Phase II clinical trial

PubMed Central

Israeli, E; Goldin, E; Fishman, S; Konikoff, F; Lavy, A; Chowers, Y; Melzer, E; Lahat, A; Mahamid, M; Shirin, H; Nussinson, E; Segol, O; Ya’acov, A Ben; Shabbat, Y; Ilan, Y

2015-01-01

Therapy for Crohn’s disease (CD) with thiopurines is limited by systemic side effects. A novel formulation of fixed-dose, delayed-release 6-mercaptopurine (DR-6MP) was developed, with local effect on the gut immune system and minimal absorption. The aim of this study was to evaluate the safety and efficacy of DR-6MP in patients with moderately severe CD compared to systemically delivered 6-mercaptopurine (Purinethol). Seventy CD patients were enrolled into a 12-week, double-blind controlled trial. The primary end-point was the percentage of subjects with clinical remission [Crohn’s Disease Activity Index (CDAI) < 150] or clinical response (100-point CDAI reduction). Twenty-six (56·5%) and 13 (54·2%) subjects from the DR-6MP and Purinethol cohorts, respectively, completed the study. DR-6MP had similar efficacy to Purinethol following 12 weeks of treatment. However, the time to maximal clinical response was 8 weeks for DR-6MP versus 12 weeks for Purinethol. A higher proportion of patients on DR-6MP showed clinical remission at week 8. A greater improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) score was noted in the DR-6MP group. DR-6MP led to a decrease of CD62+ expression on T cells, implying a reduction of lymphocyte adhesion to site of inflammation. DR-6MP was safer than Purinethol, with significantly fewer adverse events (AEs). There was no evidence of drug-induced leucopenia in the DR-6MP group; the proportion of subjects who developed hepatotoxicity was lower for the DR-6MP. Non-absorbable DR-6MP is safe and biologically active in the gut. It is clinically effective, exerting a systemic immune response with low systemic bioavailability and a low incidence of side effects. PMID:25846055

Oral administration of non-absorbable delayed release 6-mercaptopurine is locally active in the gut, exerts a systemic immune effect and alleviates Crohn's disease with low rate of side effects: results of double blind Phase II clinical trial.

PubMed

Israeli, E; Goldin, E; Fishman, S; Konikoff, F; Lavy, A; Chowers, Y; Melzer, E; Lahat, A; Mahamid, M; Shirin, H; Nussinson, E; Segol, O; Ya'acov, A Ben; Shabbat, Y; Ilan, Y

2015-08-01

Therapy for Crohn's disease (CD) with thiopurines is limited by systemic side effects. A novel formulation of fixed-dose, delayed-release 6-mercaptopurine (DR-6MP) was developed, with local effect on the gut immune system and minimal absorption. The aim of this study was to evaluate the safety and efficacy of DR-6MP in patients with moderately severe CD compared to systemically delivered 6-mercaptopurine (Purinethol). Seventy CD patients were enrolled into a 12-week, double-blind controlled trial. The primary end-point was the percentage of subjects with clinical remission [Crohn's Disease Activity Index (CDAI) < 150] or clinical response (100-point CDAI reduction). Twenty-six (56·5%) and 13 (54·2%) subjects from the DR-6MP and Purinethol cohorts, respectively, completed the study. DR-6MP had similar efficacy to Purinethol following 12 weeks of treatment. However, the time to maximal clinical response was 8 weeks for DR-6MP versus 12 weeks for Purinethol. A higher proportion of patients on DR-6MP showed clinical remission at week 8. A greater improvement in Inflammatory Bowel Disease Questionnaire (IBDQ) score was noted in the DR-6MP group. DR-6MP led to a decrease of CD62(+) expression on T cells, implying a reduction of lymphocyte adhesion to site of inflammation. DR-6MP was safer than Purinethol, with significantly fewer adverse events (AEs). There was no evidence of drug-induced leucopenia in the DR-6MP group; the proportion of subjects who developed hepatotoxicity was lower for the DR-6MP. Non-absorbable DR-6MP is safe and biologically active in the gut. It is clinically effective, exerting a systemic immune response with low systemic bioavailability and a low incidence of side effects. © 2015 British Society for Immunology.

Acute psychosocial stress and children's memory.

PubMed

de Veld, Danielle M J; Riksen-Walraven, J Marianne; de Weerth, Carolina

2014-07-01

We investigated whether children's performance on working memory (WM) and delayed retrieval (DR) tasks decreased after stress exposure, and how physiological stress responses related to performance under stress. About 158 children (83 girls; Mage = 10.61 years, SD = 0.52) performed two WM tasks (WM forward and WM backward) and a DR memory task first during a control condition, and 1 week later during a stress challenge. Salivary alpha-amylase (sAA) and cortisol were assessed during the challenge. Only WM backward performance declined over conditions. Correlations between physiological stress responses and performance within the stress challenge were present only for WM forward and DR. For WM forward, higher cortisol responses were related to better performance. For DR, there was an inverted U-shape relation between cortisol responses and performance, as well as a cortisol × sAA interaction, with concurrent high or low responses related to optimal performance. This emphasizes the importance of including curvilinear and interaction effects when relating physiology to memory.

Eating habits modulate short term memory and epigenetical regulation of brain derived neurotrophic factor in hippocampus of low- and high running capacity rats.

PubMed

Torma, Ferenc; Bori, Zoltan; Koltai, Erika; Felszeghy, Klara; Vacz, Gabriella; Koch, Lauren; Britton, Steven; Boldogh, Istvan; Radak, Zsolt

2014-08-01

Exercise capacity and dietary restriction (DR) are linked to improved quality of life, including enhanced brain function and neuro-protection. Brain derived neurotrophic factor (BDNF) is one of the key proteins involved in the beneficial effects of exercise on brain. Low capacity runner (LCR) and high capacity runner (HCR) rats were subjected to DR in order to investigate the regulation of BDNF. HCR-DR rats out-performed other groups in a passive avoidance test. BDNF content increased significantly in the hippocampus of HCR-DR groups compared to control groups (p<0.05). The acetylation of H3 increased significantly only in the LCR-DR group. However, chip-assay revealed that the specific binding between acetylated histone H3 and BNDF promoter was increased in both LCR-DR and HCR-DR groups. In spite of these increases in binding, at the transcriptional level only, the LCR-DR group showed an increase in BDNF mRNA content. Additionally, DR also induced the activity of cAMP response element-binding protein (CREB), while the content of SIRT1 was not altered. Peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) was elevated in HCR-DR groups. But, based on the levels of nuclear respiratory factor-1 and cytocrome c oxidase, it appears that DR did not cause mitochondrial biogenesis. The data suggest that DR-mediated induction of BDNF levels includes chromatin remodeling. Moreover, DR does not induce mitochondrial biogenesis in the hippocampus of LCR/HCR rats. DR results in different responses to a passive avoidance test, and BDNF regulation in LCR and HCR rats. Copyright © 2014 Elsevier Inc. All rights reserved.

Flexible stocking strategies for adapting to climatic variability

USDA-ARS?s Scientific Manuscript database

As a result of precipitation-induced variability on forage production, ranchers have difficulty matching animal demand with forage availability in their operations. Flexible stocking strategies could more effectively use extra forage in highly productive years and limit risk of overgrazing during dr...

Thinking Differentially: A Response to Issues in Differential Response

ERIC Educational Resources Information Center

Fluke, John D.; Merkel-Holguin, Lisa; Schene, Patricia

2013-01-01

This is a response to the document by Hughes et al. in this issue that offers a critique of the status of differential response (DR). We find the document to be helpful in intent, but do not find that it reflects scientifically sound methods, and contains many mischaracterizations of the status, impetus, research, and evaluation of DR to date. We…

Human leucocyte antigen (HLA-DR) gene expression is reduced in sepsis and correlates with impaired TNFα response: A diagnostic tool for immunosuppression?

PubMed Central

Winkler, Martin Sebastian; Rissiek, Anne; Priefler, Marion; Schwedhelm, Edzard; Robbe, Linda; Bauer, Antonia; Zahrte, Corinne; Zoellner, Christian; Kluge, Stefan; Nierhaus, Axel

2017-01-01

Background Sepsis is defined as a dysregulated immune response to infection. Impaired immune response in sepsis, often described as endotoxin tolerance, is characterized by unresponsiveness of monocytes on lipopolysaccharide (LPS) stimulation to release tumor necrosis factor α (TNFα). Furthermore, decreased monocyte surface protein expression of human leucocyte antigen DR (HLA-DR) is a marker for changes of the innate immune response during sepsis. Quantitative polymerase chain reaction (qPCR) and flow-cytometry (FACS) have been used to measure protein or gene expression of HLA-DR. We aimed to determine whether changes in mRNA expression of HLA-DR are associated with impaired TNFα response in human sepsis. Methods Surface protein together with mRNA expression of HLA-DR were measured by FACS and qPCR in a cohort of 9 sepsis patients and compared to 10 pre-operative control patients in a prospective study. In addition, 20 patients with post-surgical inflammation, 20 patients with sepsis or septic shock were included and TNFα was determined following ex vivo stimulation of whole blood with 500 pg/mL LPS. Total RNA was prepared from whole blood and subjected to qPCR analysis for expression analysis of HLA-DR alpha (HLA-DRA) to correlate TNFα response with HLA-DRA expression. Results Patients with sepsis presented higher numbers of monocytes in peripheral blood (P<0.001) but decreased surface protein and mRNA HLA-DR levels when compared to controls. In all patients mRNA expression of HLA-DRA was decreased by approximately 70% compared to controls (P<0.01) and was lowest in patients with sepsis or septic shock (P<0.01). TNFα response to LPS was decreased in all patients (median 319 pg/mL versus controls 1256 pg/mL; P<0.01) and lowest in patients with sepsis or septic shock (median 128 pg/mL; P<0.01). HLA-DRA correlated positively with TNFα response in all study participants (r +0.60, P<0.001) and within patients (r +0.67, P<0.001). The TNFα:HLA-DRA ratio correlated negatively with severity and the Sequential Organ Failure Assessment (SOFA) score (Spearman’s rho -0.59, P<0.001) Conclusion In this study, HLA-DRA expression was associated with a functional assay of the innate immune response. Future interventional studies aimed at the immune response during sepsis could make use of these methods for optimizing target groups based on biological plausibility and intervention effectiveness. PMID:28771573

Human leucocyte antigen (HLA-DR) gene expression is reduced in sepsis and correlates with impaired TNFα response: A diagnostic tool for immunosuppression?

PubMed

Winkler, Martin Sebastian; Rissiek, Anne; Priefler, Marion; Schwedhelm, Edzard; Robbe, Linda; Bauer, Antonia; Zahrte, Corinne; Zoellner, Christian; Kluge, Stefan; Nierhaus, Axel

2017-01-01

Sepsis is defined as a dysregulated immune response to infection. Impaired immune response in sepsis, often described as endotoxin tolerance, is characterized by unresponsiveness of monocytes on lipopolysaccharide (LPS) stimulation to release tumor necrosis factor α (TNFα). Furthermore, decreased monocyte surface protein expression of human leucocyte antigen DR (HLA-DR) is a marker for changes of the innate immune response during sepsis. Quantitative polymerase chain reaction (qPCR) and flow-cytometry (FACS) have been used to measure protein or gene expression of HLA-DR. We aimed to determine whether changes in mRNA expression of HLA-DR are associated with impaired TNFα response in human sepsis. Surface protein together with mRNA expression of HLA-DR were measured by FACS and qPCR in a cohort of 9 sepsis patients and compared to 10 pre-operative control patients in a prospective study. In addition, 20 patients with post-surgical inflammation, 20 patients with sepsis or septic shock were included and TNFα was determined following ex vivo stimulation of whole blood with 500 pg/mL LPS. Total RNA was prepared from whole blood and subjected to qPCR analysis for expression analysis of HLA-DR alpha (HLA-DRA) to correlate TNFα response with HLA-DRA expression. Patients with sepsis presented higher numbers of monocytes in peripheral blood (P<0.001) but decreased surface protein and mRNA HLA-DR levels when compared to controls. In all patients mRNA expression of HLA-DRA was decreased by approximately 70% compared to controls (P<0.01) and was lowest in patients with sepsis or septic shock (P<0.01). TNFα response to LPS was decreased in all patients (median 319 pg/mL versus controls 1256 pg/mL; P<0.01) and lowest in patients with sepsis or septic shock (median 128 pg/mL; P<0.01). HLA-DRA correlated positively with TNFα response in all study participants (r +0.60, P<0.001) and within patients (r +0.67, P<0.001). The TNFα:HLA-DRA ratio correlated negatively with severity and the Sequential Organ Failure Assessment (SOFA) score (Spearman's rho -0.59, P<0.001). In this study, HLA-DRA expression was associated with a functional assay of the innate immune response. Future interventional studies aimed at the immune response during sepsis could make use of these methods for optimizing target groups based on biological plausibility and intervention effectiveness.

The medical movement and Dr. Ismael Cosío Villegas. At half a century.

PubMed

Sandoval-Gutiérrez, José Luis

2018-01-01

In 1964, medical residents and interns of the Mexican Republic decided to carry out a work stoppage that stretched over for several months. Several prominent doctors decided to join the causes that motivated the movement, among which Dr. Ismael Cosío Villegas, who at that moment was the director general of the Huipulco hospital for tuberculosis patients; his participation and dedication are historical, and his determination caused for his resignation to be demanded. His trajectory remains practically unknown by the medical community. Copyright: © 2018 SecretarÍa de Salud.

Dietary restriction involves NAD⁺ -dependent mechanisms and a shift toward oxidative metabolism.

PubMed

Moroz, Natalie; Carmona, Juan J; Anderson, Edward; Hart, Anne C; Sinclair, David A; Blackwell, T Keith

2014-12-01

Interventions that slow aging and prevent chronic disease may come from an understanding of how dietary restriction (DR) increases lifespan. Mechanisms proposed to mediate DR longevity include reduced mTOR signaling, activation of the NAD⁺ -dependent deacylases known as sirtuins, and increases in NAD⁺ that derive from higher levels of respiration. Here, we explored these hypotheses in Caenorhabditis elegans using a new liquid feeding protocol. DR lifespan extension depended upon a group of regulators that are involved in stress responses and mTOR signaling, and have been implicated in DR by some other regimens [DAF-16 (FOXO), SKN-1 (Nrf1/2/3), PHA-4 (FOXA), AAK-2 (AMPK)]. Complete DR lifespan extension required the sirtuin SIR-2.1 (SIRT1), the involvement of which in DR has been debated. The nicotinamidase PNC-1, a key NAD⁺ salvage pathway component, was largely required for DR to increase lifespan but not two healthspan indicators: movement and stress resistance. Independently of pnc-1, DR increased the proportion of respiration that is coupled to ATP production but, surprisingly, reduced overall oxygen consumption. We conclude that stress response and NAD⁺ -dependent mechanisms are each critical for DR lifespan extension, although some healthspan benefits do not require NAD⁺ salvage. Under DR conditions, NAD⁺ -dependent processes may be supported by a DR-induced shift toward oxidative metabolism rather than an increase in total respiration. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

Dietary regulation of hypodermal polyploidization in C. elegans

PubMed Central

Tain, Luke S; Lozano, Encarnación; Sáez, Alberto G; Leroi, Armand M

2008-01-01

Background Dietary restriction (DR) results in increased longevity, reduced fecundity and reduced growth in many organisms. Though many studies have examined the effects of DR on longevity and fecundity, few have investigated the effects on growth. Results Here we use Caenorhabditis elegans to determine the mechanisms that regulate growth under DR. We show that rather than a reduction in cell number, decreased growth in wild type C. elegans under DR is correlated with lower levels of hypodermal polyploidization. We also show that mutants lacking wild type sensory ciliated neurons are small, exhibit hypo-polyploidization and more importantly, when grown under DR, reduce their levels of endoreduplication to a lesser extent than wild type, suggesting that these neurons are required for the regulation of hypodermal polyploidization in response to DR. Similarly, we also show that the cGMP-dependent protein kinase EGL-4 and the SMA/MAB signalling pathway regulate polyploidization under DR. Conclusion We show C. elegans is capable of actively responding to food levels to regulate adult ploidy. We suggest this response is dependent on the SMA/MAB signalling pathway. PMID:18366811

Dietary regulation of hypodermal polyploidization in C. elegans.

PubMed

Tain, Luke S; Lozano, Encarnación; Sáez, Alberto G; Leroi, Armand M

2008-03-12

Dietary restriction (DR) results in increased longevity, reduced fecundity and reduced growth in many organisms. Though many studies have examined the effects of DR on longevity and fecundity, few have investigated the effects on growth. Here we use Caenorhabditis elegans to determine the mechanisms that regulate growth under DR. We show that rather than a reduction in cell number, decreased growth in wild type C. elegans under DR is correlated with lower levels of hypodermal polyploidization. We also show that mutants lacking wild type sensory ciliated neurons are small, exhibit hypo-polyploidization and more importantly, when grown under DR, reduce their levels of endoreduplication to a lesser extent than wild type, suggesting that these neurons are required for the regulation of hypodermal polyploidization in response to DR. Similarly, we also show that the cGMP-dependent protein kinase EGL-4 and the SMA/MAB signalling pathway regulate polyploidization under DR. We show C. elegans is capable of actively responding to food levels to regulate adult ploidy. We suggest this response is dependent on the SMA/MAB signalling pathway.

Association of HLA-DR1 with the allergic response to the major mugwort pollen allergen: molecular background.

PubMed

Knapp, Bernhard; Fischer, Gottfried; Van Hemelen, Dries; Fae, Ingrid; Maillere, Bernard; Ebner, Christof; Schreiner, Wolfgang; Bohle, Barbara; Jahn-Schmid, Beatrice

2012-08-08

Mugwort pollen allergens represent the main cause of pollinosis in late summer. The major allergen, Art v 1, contains only one single immunodominant, solely HLA-DR-restricted T cell epitope (Art v 125-36). The frequency of HLA-DRB1*01 is highly increased in mugwort-allergic individuals and HLA-DR1 serves as restriction element for Art v 125-36. However, Art v 125-36 also binds to HLA-DR4 with high affinity and DR1-restricted Art v 125-36 -specific T cell receptors can be activated by HLA-DR4 molecules. To understand the predominance of HLA-DR1 in mugwort allergy in spite of the degeneracy in HLA/peptide-binding and TCR-recognition, we investigated the molecular background of Art v 125-36 /MHC/TCR interactions in the context of HLA-DR1 compared to -DR4. The majority of Art v 125-36 -specific T cell lines and clones from HLA-DR1 carrying, mugwort pollen-allergic donors reacted to synthetic and naturally processed Art v 1-peptides when presented by HLA-DR1 or HLA-DR4 expressing antigen presenting cells. However, at limiting peptide concentrations DR1 was more effective in T cell stimulation. In addition, the minimal epitope for 50% of Art v 125-36 -specific T cells was shorter for DR1 than for DR4. In vitro binding assays of Art v 125-36 mutant peptides to isolated DR1- and DR4-molecules indicated similar binding capacities and use of the same register. In silico simulation of Art v 125-36 binding to HLA-DR1 and -DR4 suggested similar binding of the central part of the peptide to either molecule, but a higher flexibility of the N- and C-terminal amino acids and detachment at the C-terminus in HLA-DR1. The predominance of HLA-DR1 in the response to Art v 125-36 may be explained by subtle conformation changes of the peptide bound to DR1 compared to DR4. Computer simulation supported our experimental data by demonstrating differences in peptide mobility within the HLA-DR complex that may influence TCR-binding. We suggest that the minor differences observed in vitro may be more relevant in the microenvironment in vivo, so that only presentation by HLA-DR1, but not -DR4 permits successful T cell activation.

Reply to Lawrence R. Solomon: Negative interaction of high folate status with biochemical and neurological response to vitamin B-12 treatment

USDA-ARS?s Scientific Manuscript database

We thank Dr. Lawrence Solomon for his observations and comments regarding our recent article on biochemical and neurological responses to vitamin B-12 treatment in asymptomatic Chilean elderly (1). Our article highlighted the most important effects of treatment; in our response to Dr. Solomon’s ques...

Hydrostatic Response of Submarine Nickel Aluminum Bronze Valves with Corrosion Damage

DTIC Science & Technology

2008-07-01

Engineering PO Box 1000 Halifax, Nova Scotia B3J 2X4 Project Manager: Dr. T.S. Koko , 902-425-5101 Contract Number: W7707-078022/001/HAL Contract...Manager: Dr. T.S. Koko , 902-425-5101 ext 243 Contract Number: W7707-078022/001/HAL Contract Scientific Authority: Dr. Y. Wang, 902-427-3035...Hydrostatic Response of Submarine Nickel Aluminum Bronze Valves with Corrosion Damage B.K.C. Yuen; T.S. Koko ; R. Warner; DRDC Atlantic CR 2008

Modeling of GE Appliances: Cost Benefit Study of Smart Appliances in Wholesale Energy, Frequency Regulation, and Spinning Reserve Markets

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

Fuller, Jason C.; Parker, Graham B.

This report is the second in a series of three reports describing the potential of GE’s DR-enabled appliances to provide benefits to the utility grid. The first report described the modeling methodology used to represent the GE appliances in the GridLAB-D simulation environment and the estimated potential for peak demand reduction at various deployment levels. The third report will explore the technical capability of aggregated group actions to positively impact grid stability, including frequency and voltage regulation and spinning reserves, and the impacts on distribution feeder voltage regulation, including mitigation of fluctuations caused by high penetration of photovoltaic distributed generation.more » In this report, a series of analytical methods were presented to estimate the potential cost benefit of smart appliances while utilizing demand response. Previous work estimated the potential technical benefit (i.e., peak reduction) of smart appliances, while this report focuses on the monetary value of that participation. The effects on wholesale energy cost and possible additional revenue available by participating in frequency regulation and spinning reserve markets were explored.« less

The influence of differential response on decision-making in child protective service agencies.

PubMed

Janczewski, Colleen E

2015-01-01

Differential response (DR) profoundly changes the decision pathways of public child welfare systems, yet little is known about how DR shapes the experiences of children whose reports receive an investigation rather than an alternate response. Using data from the National Child Abuse and Neglect Data System (NCANDS), this study examined the relationship between DR implementation and decision outcomes in neglect cases, as measured by investigation, substantiation, and removal rates in 297 U.S. counties. Multivariate regression models included county-level measures of child poverty and proportions of African American children. Path analyses were also conducted to identify mediating effects of prior decision points and moderating effects of DR on poverty and race's influence on decision outcomes. Results indicate that compared to non-DR counties, those implementing DR have significantly lower investigation and substantiation rates within county populations but higher substantiation rates among investigated cases. Regression models showed significant reductions in removal rates associated with DR implementation, but these effects became insignificant in path models that accounted for mediation effects of previous decision points. Findings also suggest that DR implementation may reduce the positive association between child poverty rates and investigation rates, but additional studies with larger samples are needed to confirm this moderation effect. Two methods of calculating decision outcomes, population- and decision-based enumeration, were used, and policy and research implications of each are discussed. This study demonstrates that despite their inherit complexity, large administrative datasets such as NCANDS can be used to assess the impact of wide-scale system change across jurisdictions. Copyright © 2014 Elsevier Ltd. All rights reserved.

T7-RNA Polymerase

NASA Technical Reports Server (NTRS)

1997-01-01

T7-RNA Polymerase grown on STS-81. Structure-Function Relationships of RNA Polymerase: DNA-dependent RNA polymerase is the key enzyme responsible for the biosynthesis of RNA, a process known as transcription. Principal Investigator's include Dr. Dan Carter, Dr. B.C. Wang, and Dr. John Rose of New Century Pharmaceuticals.

Testimony by Melissa Reeves

ERIC Educational Resources Information Center

Communique, 2010

2010-01-01

This article presents the testimony by Dr. Melissa Reeves, a school psychologist and faculty member in the school psychology program at Winthrop University. Dr. Reeves shares her view of the critical role schools must play in crisis response and recovery. In addition to being a graduate educator and a consulting school psychologist, Dr. Reeves is…

Dynamic Reciprocity in the Wound Microenvironment

PubMed Central

Schultz, Gregory S.; Davidson, Jeffrey M.; Kirsner, Robert S.; Bornstein, Paul; Herman, Ira M.

2011-01-01

Here, we define dynamic reciprocity (DR) as an ongoing, bidirectional interaction amongst cells and their surrounding microenvironment. In the review, we posit that DR is especially meaningful during wound healing as the DR-driven biochemical, biophysical and cellular responses to injury play pivotal roles in regulating tissue regenerative responses. Such cell-extracellular matrix interactions not only guide and regulate cellular morphology, but cellular differentiation, migration, proliferation, and survival during tissue development, including e.g. embryogenesis, angiogenesis, as well as during pathologic processes including cancer diabetes, hypertension and chronic wound healing. Herein, we examine DR within the wound microenvironment while considering specific examples across acute and chronic wound healing. This review also considers how a number of hypotheses that attempt to explain chronic wound pathophysiology, which may be understood within the DR framework. The implications of applying the principles of dynamic reciprocity to optimize wound care practice and future development of innovative wound healing therapeutics are also briefly considered. PMID:21362080

IN2 Profile: Go Electric Provides Grid Stabilizing Energy Service Solutions to Utilities

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

Pless, Shanti

Through the Wells Fargo Innovation Incubator (IN²) program, Go Electric will validate their Link DR technology, which is an advanced, uninterruptable power supply that provides secure power, lowers facility energy costs, integrates renewables, and generates income from utility demand response programs. The IN² program launched in October 2014 and is part of Wells Fargo’s 2020 Environmental Commitment to provide $100 million to environmentally-focused nonprofits and universities. The goal is to create an ecosystem that fosters and accelerates the commercialization of promising commercial buildings technologies that can provide scalable solutions to reduce the energy impact of buildings. According to the Departmentmore » of Energy, nearly 40 percent of energy consumption in the U.S. today comes from buildings at an estimated cost of $413 billion.« less

Item Construction and Psychometric Models Appropriate for Constructed Responses

DTIC Science & Technology

1991-08-01

which involve only one attribute per item. This is especially true when we are dealing with constructed-response items, we have to measure much more...Service University of Ilinois Educacional Testing Service Rosedal Road Capign. IL 61801 Princeton. K3 08541 Princeton. N3 08541 Dr. Charles LeiS Dr

The GLIMPSE project: Exploring strategies for meeting energy, environmental and climate objectives

EPA Science Inventory

Many of Chinas cities are struggling with high levels of air pollution. At the same time, Chinese planners are seeking to meet growing demands for energy in a manner that meets climate goals. In this presentation, Dr. Loughlin describes the linkages between energy, the environmen...

Physical Theatre Education: Beyond Knowledge Transfer

ERIC Educational Resources Information Center

Gaines, Andrew M.

2016-01-01

Teaching physical theatre successfully relies on a reverence for the human soul in order to cultivate risk-forward embodiment while demanding technical precision. In an effort to illuminate such praxis, this article documents and analyzes the experiences of novice physical theatre performers guided by master teaching artist and performer, Dr.…

Alterations in perivascular innervation function in mesenteric arteries from offspring of diabetic rats

PubMed Central

de Queiroz, D B; Sastre, E; Caracuel, L; Callejo, M; Xavier, F E; Blanco-Rivero, J; Balfagón, G

2015-01-01

Background and Purpose We have reported that exposure to a diabetic intrauterine environment during pregnancy increases blood pressure in adult offspring, but the mechanisms involved are not completely understood. This study was designed to analyse a possible role of perivascular sympathetic and nitrergic innervation in the superior mesenteric artery (SMA) in this effect. Experimental Approach Diabetes was induced in pregnant Wistar rats by a single injection of streptozotocin. Endothelium-denuded vascular rings from the offspring of control (O-CR) and diabetic rats (O-DR) were used. Vasomotor responses to electrical field stimulation (EFS), NA and the NO donor DEA-NO were studied. The expressions of neuronal NOS (nNOS) and phospho-nNOS (P-nNOS) and release of NA, ATP and NO were determined. Sympathetic and nitrergic nerve densities were analysed by immunofluorescence. Key Results Blood pressure was higher in O-DR animals. EFS-induced vasoconstriction was greater in O-DR animals. This response was decreased by phentolamine more in O-DR animals than their controls. L-NAME increased EFS-induced vasoconstriction more strongly in O-DR than in O-CR segments. Vasomotor responses to NA or DEA-NO were not modified. NA, ATP and NO release was increased in segments from O-DR. nNOS expression was not modified, whereas P-nNOS expression was increased in O-DR. Sympathetic and nitrergic nerve densities were similar in both experimental groups. Conclusions and Implications The activity of sympathetic and nitrergic innervation is increased in SMA from O-DR animals. The net effect is an increase in EFS-induced contractions in these animals. These effects may contribute to the increased blood pressure observed in the offspring of diabetic rats. PMID:26177571

CD14+ CD15- HLA-DR- myeloid-derived suppressor cells impair antimicrobial responses in patients with acute-on-chronic liver failure.

PubMed

Bernsmeier, Christine; Triantafyllou, Evangelos; Brenig, Robert; Lebosse, Fanny J; Singanayagam, Arjuna; Patel, Vishal C; Pop, Oltin T; Khamri, Wafa; Nathwani, Rooshi; Tidswell, Robert; Weston, Christopher J; Adams, David H; Thursz, Mark R; Wendon, Julia A; Antoniades, Charalambos Gustav

2018-06-01

Immune paresis in patients with acute-on-chronic liver failure (ACLF) accounts for infection susceptibility and increased mortality. Immunosuppressive mononuclear CD14 + HLA-DR - myeloid-derived suppressor cells (M-MDSCs) have recently been identified to quell antimicrobial responses in immune-mediated diseases. We sought to delineate the function and derivation of M-MDSC in patients with ACLF, and explore potential targets to augment antimicrobial responses. Patients with ACLF (n=41) were compared with healthy subjects (n=25) and patients with cirrhosis (n=22) or acute liver failure (n=30). CD14 + CD15 - CD11b + HLA-DR - cells were identified as per definition of M-MDSC and detailed immunophenotypic analyses were performed. Suppression of T cell activation was assessed by mixed lymphocyte reaction. Assessment of innate immune function included cytokine expression in response to Toll-like receptor (TLR-2, TLR-4 and TLR-9) stimulation and phagocytosis assays using flow cytometry and live cell imaging-based techniques. Circulating CD14 + CD15 - CD11b + HLA-DR - M-MDSCs were markedly expanded in patients with ACLF (55% of CD14+ cells). M-MDSC displayed immunosuppressive properties, significantly decreasing T cell proliferation (p=0.01), producing less tumour necrosis factor-alpha/interleukin-6 in response to TLR stimulation (all p<0.01), and reduced bacterial uptake of Escherichia coli (p<0.001). Persistently low expression of HLA-DR during disease evolution was linked to secondary infection and 28-day mortality. Recurrent TLR-2 and TLR-4 stimulation expanded M-MDSC in vitro. By contrast, TLR-3 agonism reconstituted HLA-DR expression and innate immune function ex vivo. Immunosuppressive CD14 + HLA-DR - M-MDSCs are expanded in patients with ACLF. They were depicted by suppressing T cell function, attenuated antimicrobial innate immune responses, linked to secondary infection, disease severity and prognosis. TLR-3 agonism reversed M-MDSC expansion and innate immune function and merits further evaluation as potential immunotherapeutic agent. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Modeling Incorrect Responses to Multiple-Choice Items with Multilinear Formula Score Theory.

DTIC Science & Technology

1987-08-01

Eisenhower Avenue University of Leyden Alexandria, VA 22333 Education Research Center Boerhaavelaan 2 Dr. John M. Eddins 2334 EN Leyden University of...22302-0268 Dr. William Montague NPRDC Code 13 Dr. William L. Maloy San Diego, CA 92152-6800 Chief of Naval Education and Training Ms. Kathleen Moreno

An Investigation of Methods for Reducing Sampling Error in Certain IRT (Item Response Theory) Procedures.

DTIC Science & Technology

1983-08-01

34th Streets Lawrence, KS 66045 Baltimore, MD 21218 ENIC Facility-Acquisitions 1 Dr. Ron Hambleton 4t33 Rugby Avenue School of Education Lcthesda, !ID...Sector Dr. V. R. R. Uppuluri 1 Dr. Rand R. Wilcox Union Carbide Corporation University of Southern California Nuclear Division Department of

Modeling Item Responses When Different Subjects Employ Different Solution Strategies.

DTIC Science & Technology

1987-10-01

Crombag Dr. Stephen Dunbar University of Leyden Lindquist Center Education Research l-enter for Measurement Boerhaavelaan 2 University of Iowa 2334 EN... Leyden Iowa City, IA 52242 The NEFHlPLANDS Dr. James A. F.arles Mr. Iimothy Davey Air Force Human Resources Lab iJniversity of Illinois Brooks AFB, TX...Education and Training Dr. William Montague Naval Air Station NPRDC Code 13 Pensacola, fL 32508 San Diego, CA 92152-6800 Dr. Gary Marco Ms. Kathleen Moreno

Models and Estimation Procedures for the Analysis of Subjects-by-Items Data Arrays.

DTIC Science & Technology

1982-06-30

Conclusions and recommendations The usefulness of Tukey’s model for model-based psychological testing is probably greatest for analyses of responses which are...22314 National Institute of Education Attn: TC 1200 19th Street NW Washington, DC 20208 Dr. William Graham Testing Directorate 1 Dr. Lorraine D. Eyde ...Educational Testing Service 1 Dr. Norman Cliff Princeton, NJ 08450 Dept. of Psychology Univ. of So. California 1 Dr. Ina Bilodeau University Park

The Manifest and Latent Functions of Differential Response in Child Welfare

ERIC Educational Resources Information Center

Ji, Daniel; Sullivan, Richard

2016-01-01

Although previous research has explored the efficacy of differential response (DR) programs in child welfare, there have been no studies to date about coding decisions between designations by child protection service agencies. Research has explored client satisfaction with DR as well as rates of recidivism and removal/placement but with limited…

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

Cappers, Peter; MacDonald, Jason; Goldman, Charles

In this study, we attempt to provide a comprehensive examination of various market and policy barriers to demand response providing ancillary services in both ISO/RTO and non-ISO/RTO regions, especially at the program provider level. It is useful to classify barriers in order to create a holistic understanding and identify parties that could be responsible for their removal. This study develops a typology of barriers focusing on smaller customers that must rely on a program provider (i.e., electric investor owned utility or IOU, ARC) to create an aggregated DR resource in order to bring ancillary services to the balancing authority.ii Themore » barriers were identified through examinations of regulatory structures, market environments, and product offerings; and discussions with industry stakeholders and regulators. In order to help illustrate the differences in barriers among various wholesale market designs and their constituent retail environments, four regions were chosen to use as case studies: Colorado, Texas, Wisconsin, and New Jersey. We highlight the experience in each area as it relates to the identified barriers.« less

Sarilumab for the treatment of rheumatoid arthritis.

PubMed

Cooper, Simon

2016-01-01

Simon Cooper has >18 years of global experience in the pharmaceutical industry. He joined Sanofi in July 2014 as the Vice President, Global Project Head. In his current position at Sanofi, Dr Cooper is responsible for the clinical development of sarilumab and the worldwide submission in rheumatoid arthritis. He joined Sanofi after serving as the Global Program Medical Director at Novartis since 2012. In this role, Dr Cooper acted as the clinical lead for secukinumab psoriasis submission. Prior to Novartis, Dr Cooper held various posts at Human Genome Sciences, USA, including Executive Director of Clinical Research, Senior Director of Clinical Research and Director of Clinical Research. During his tenure at Human Genome Sciences, USA, Dr Cooper was involved in the submission of belimumab leading to its approval for SLE, and was responsible for its subsequent clinical development program. Dr Cooper has also previously held positions at MedImmune Ltd, UK, Roche, Napp Pharmaceutical Research Ltd, Wyeth Research and Medeval Ltd. In these roles, his responsibilities ranged from medical oversight of clinical trials to medical support for commercial, medical affairs and business development. He received a Bachelor of Medicine and Bachelor of Surgery from University of Newcastle upon Tyne Medical School.

STAT3/NF-κB interactions determine the level of haptoglobin expression in male rats exposed to dietary restriction and/or acute phase stimuli.

PubMed

Uskoković, Aleksandra; Dinić, Svetlana; Mihailović, Mirjana; Grdović, Nevena; Arambašić, Jelena; Vidaković, Melita; Bogojević, Desanka; Ivanović-Matić, Svetlana; Martinović, Vesna; Petrović, Miodrag; Poznanović, Goran; Grigorov, Ilijana

2012-01-01

Haptoglobin is a constitutively expressed protein which is predominantly synthesized in the liver. During the acute-phase (AP) response haptoglobin is upregulated along with other AP proteins. Its upregulation during the AP response is mediated by cis-trans interactions between the hormone-responsive element (HRE) residing in the haptoglobin gene and inducible transcription factors STAT3 and C/EBP β. In male rats that have been subjected to chronic 50% dietary restriction (DR), the basal haptoglobin serum level is decreased. The aim of this study was to characterize the trans-acting factor(s) responsible for the reduction of haptoglobin expression in male rats subjected to 50% DR for 6 weeks. Protein-DNA interactions between C/EBP and STAT families of transcription factors and the HRE region of the haptoglobin gene were examined in livers of male rats subjected to DR, as well as during the AP response that was induced by turpentine administration. In DR rats, we observed associations between the HRE and C/EBPα/β, STAT5b and NF-κB p50, and the absence of interactions between STAT3 and NF-kB p65. Subsequent induction of the AP response in DR rats by turpentine administration elicited a normal, almost 2-fold increase in the serum haptoglobin level that was accompanied by HRE-binding of C/EBPβ, STAT3/5b and NF-kB p65/p50, and the establishment of interaction between STAT3 and NF-κB p65. These results suggest that STAT3 and NF-κB p65 crosstalk plays a central role while C/EBPβ acquires an accessory role in establishing the level of haptoglobin gene expression in male rats exposed to DR and AP stimuli.

Caspar Creek ecology project, annual report, 1968-69

Treesearch

Roger A. Barnhart

1969-01-01

On March 12, 1969, Dr. Roger A. Barnhart, Leader, California Fishery Unit, agreed to take over Humboldt State College's responsibility for the Caspar Creek Project since Dr. John DeWitt, Project Supervisor, accepted a temporary Peace Corps assignment in Egypt. Dr. DeWitt agreed to write the major portion of the '68-'69 progress report. Unfortunately,...

Serum fibroblast growth factor 23 is a useful marker to distinguish vitamin D-deficient rickets from hypophosphatemic rickets.

PubMed

Kubota, Takuo; Kitaoka, Taichi; Miura, Kohji; Fujiwara, Makoto; Ohata, Yasuhisa; Miyoshi, Yoko; Yamamoto, Keiko; Takeyari, Shinji; Yamamoto, Takehisa; Namba, Noriyuki; Ozono, Keiichi

2014-01-01

Vitamin D-deficient rickets (DR) has recently re-emerged among developed countries. Vitamin D deficiency can influence biochemical results of patients with fibroblast growth factor 23 (FGF23)-related hereditary hypophosphatemic rickets (HR), making differential diagnosis difficult. In the present study we evaluated the utility of serum FGF23 levels in the diagnosis of DR and during its treatment. The study group comprised 24 children with DR and 8 children with HR. Serum FGF23 levels and bone metabolism-related measurements were assessed. Serum FGF23 levels in patients with DR were less than 19 pg/ml, while those in patients with HR were more than 57 pg/ml. There were significant differences in serum levels of calcium, phosphate, parathyroid hormone, and 1,25-dihydroxyvitamin D, as well as tubular maximum phosphate reabsorption per glomerular filtration rate between patients with DR and HR, but these values were not fully mutually exclusive. In addition, serum FGF23 and phosphate levels were increased following treatment. Serum FGF23 level is the most critical biochemical marker for distinguishing DR from HR and might be a good indicator of biochemical response to the intervention. Serum FGF23 levels show utility for the diagnosis of DR and in the assessment of its response to treatment.

Expression of Death Receptor 4 Is Positively Regulated by MEK/ERK/AP-1 Signaling and Suppressed upon MEK Inhibition*

PubMed Central

Yao, Weilong; Oh, You-Take; Deng, Jiusheng; Yue, Ping; Deng, Liang; Huang, Henry; Zhou, Wei; Sun, Shi-Yong

2016-01-01

Death receptor 4 (DR4) is a cell surface receptor for tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and triggers apoptosis upon ligation with TRAIL or aggregation. MEK/ERK signaling is a well known and the best-studied effector pathway downstream of Ras and Raf. This study focuses on determining the impact of pharmacological MEK inhibition on DR4 expression and elucidating the underlying mechanism. We found that several MEK inhibitors including MEK162, AZD6244, and PD0325901 effectively decreased DR4 protein levels including cell surface DR4 in different cancer cell lines. Accordingly, pre-treatment of TRAIL-sensitive cancer cell lines with a MEK inhibitor desensitized them to TRAIL-induced apoptosis. These results indicate that MEK inhibition negatively regulates DR4 expression and cell response to TRAIL-induced apoptosis. MEK inhibitors did not alter DR4 protein stability, rather decreased its mRNA levels, suggesting a transcriptional regulation. In contrast, enforced activation of MEK/ERK signaling by expressing ectopic B-Raf (V600E) or constitutively activated MEK1 (MEK1-CA) or MEK2 (MEK2-CA) activated ERK and increased DR4 expression; these effects were inhibited when a MEK inhibitor was present. Promoter analysis through deletion and mutation identified the AP-1 binding site as an essential response element for enhancing DR4 transactivation by MEK1-CA. Furthermore, inhibition of AP-1 by c-Jun knockdown abrogated the ability of MEK1-CA to increase DR4 promoter activity and DR4 expression. These results suggest an essential role of AP-1 in mediating MEK/ERK activation-induced DR4 expression. Our findings together highlight a previously undiscovered mechanism that positively regulates DR4 expression through activation of the MEK/ERK/AP-1 signaling pathway. PMID:27576686

20 Years of Archival Ambition

ERIC Educational Resources Information Center

Byrne, Richard

2007-01-01

In this article, the author presents an interview with Thomas F. Staley, director of the Harry Ransom Humanities Research Center at the University of Texas. This interview touches on many issues that have cropped up in his long stay at the helm of the center, where Dr. Staley juggles the demands of multiple constituencies that include scholars,…

Genotype and environment effects on ethanol yield from pearl millet

USDA-ARS?s Scientific Manuscript database

In spite of rising feedstock costs and the grain-deficit status of the southeast, investors have committed to the construction of new ethanol plants in the region. The use of alternative feedstocks will help to alleviate market demand for corn both as a feedgrain and as an ethanol feedstock. As a dr...

How Can We Improve the Measurement of "Non-Academic" Competencies?

ERIC Educational Resources Information Center

Halpin, Peter F.

2017-01-01

The target paper, "Rethinking Traditional Methods of Survey Validation" (Andrew Maul), raises some interesting critical ideas, both old and new, about the validation of self-report surveys. As indicated by Dr. Maul, recent policy initiatives in the United States (e.g., ESSA) have led to a demand for assessments of…

Examining Teacher Attrition and Other Related Issues: A Conversation with Dr. D. Ray Reutzel

ERIC Educational Resources Information Center

Martin, Linda E.; Mulvihill, Thalia M.

2016-01-01

Teacher educators work diligently to prepare future teachers while navigating the surrounding political realities that challenge our schools. Demands placed on teacher educators are growing and are increasingly more complex. Well-prepared and successful teachers are exiting the profession at alarming rates in several places in the world, including…

Barriers and Opportunities to Broader Adoption of Integrated Demand Side Management at Electric Utilities: A Scoping Study

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

Potter, Jennifer; Stuart, Elizabeth; Cappers, P

Integrated demand-side management (IDSM) is a strategic approach to designing and delivering a portfolio of demand side management (DSM) programs to customers. IDSM typically delivers customer centric strategies with the goal of increasing the amount of DSM in the field, but doing so in a way that integrates various measures and technologies to improve their collective performance and/or penetration. Specifically, IDSM can be defined as the integrated or coordinated delivery of three or more of: (1) energy efficiency (EE), (2) demand response (DR), (3) distributed generation (DG), (4) storage, (5) electric vehicle (EV) technologies, and (6) time-based rate programs tomore » residential and commercial electric utility customers. The electric industry’s limited experience deploying IDSM to date suggests that significant barriers may exist. A Berkeley Lab report “Barriers and Opportunities to Broader Adoption of Integrated Demand Side Management at Electric Utilities: A Scoping Study” explores recent electric utility experience with IDSM to provide an assessment of the barriers and potential benefits perceived or experienced by program administrators in their attempts to implement integrated programs. The research draws on surveys and interviews with eleven staff from a sample of eight DSM program administrators and program implementers who were currently implementing or had previously attempted to implement an IDSM program or initiative. Respondents provided their perspectives on drivers for IDSM and barriers to broader deployment. They also reported on actions they had undertaken to promote expanded delivery of IDSM and provided their assessments of the most important under-tapped opportunities for expanding IDSM efforts, both for program administrator and regulatory organizations.« less

The Response of Frozen Soils to Vibratory Loads

DTIC Science & Technology

1975-06-01

Construction. i | The report was technically reviewed by Dr. Y . Nakano of USA CRREL, and A.F. Müller of the Office of Chief of Engineers. Their suggestions...B.I.S. Helme, Jr., t M.J. Dabney III, F. Berrego, R.N. Lachenmaier and D.J. Coombes. Dr. T.M. Lee, Dr. D.M. Norris, Jr. and Dr. Y . Nakano gave... y /g stress static confining pressure, (a, + 2a ^/3 axial (vertical) static pressure lateral static pressure dynamic stress (peak) phase shift

The dopamine D2 receptor regulates Akt and GSK-3 via Dvl-3.

PubMed

Sutton, Laurie P; Rushlow, Walter J

2012-08-01

The dopamine D2 receptor (D2DR) regulates Akt and may also target the Wnt pathway, two signalling cascades that inhibit glycogen synthase kinase-3 (GSK-3). This study examined whether the Wnt pathway is regulated by D2DR and the role of Akt and dishevelled-3 (Dvl-3) in regulating GSK-3 and the transcription factor β-catenin in the rat brain. Western blotting showed that subchronic treatment of raclopride (D2DR antagonist) increase phosphorylated Akt, Dvl-3, GSK-3, phosphorylated GSK-3 and β-catenin, whereas subchronic treatment of quinpirole (D2DR agonist) induced the opposite response. Co-immunopreciptations revealed an association between GSK-3 and the D2DR complex that was altered following raclopride and quinpirole, albeit in opposite directions. SCH23390 (D1DR antagonist) and nafadotride (D3DR antagonist) were also used to determine if the response was specific to the D2DR. Neither subchronic treatment affected Dvl-3, GSK-3, Akt nor β-catenin protein levels, although nafadotride altered the phosphorylation state of Akt and GSK-3. In addition, in-vitro experiments were conducted to manipulate Akt and Dvl-3 activity in SH-SY5Y cells to elucidate how the pattern of change observed following manipulation of D2DR developed. Results indicate that Akt affects the phosphorylation state of GSK-3 but has no effect on β-catenin levels. However, altering Dvl-3 levels resulted in changes in Akt and the Wnt pathway similar to what was observed following raclopride or quinpirole treatment. Collectively, the data suggests that the D2DR very specifically regulates Wnt and Akt signalling via Dvl-3.

SIDD: A Semantically Integrated Database towards a Global View of Human Disease

PubMed Central

Cheng, Liang; Wang, Guohua; Li, Jie; Zhang, Tianjiao; Xu, Peigang; Wang, Yadong

2013-01-01

Background A number of databases have been developed to collect disease-related molecular, phenotypic and environmental features (DR-MPEs), such as genes, non-coding RNAs, genetic variations, drugs, phenotypes and environmental factors. However, each of current databases focused on only one or two DR-MPEs. There is an urgent demand to develop an integrated database, which can establish semantic associations among disease-related databases and link them to provide a global view of human disease at the biological level. This database, once developed, will facilitate researchers to query various DR-MPEs through disease, and investigate disease mechanisms from different types of data. Methodology To establish an integrated disease-associated database, disease vocabularies used in different databases are mapped to Disease Ontology (DO) through semantic match. 4,284 and 4,186 disease terms from Medical Subject Headings (MeSH) and Online Mendelian Inheritance in Man (OMIM) respectively are mapped to DO. Then, the relationships between DR-MPEs and diseases are extracted and merged from different source databases for reducing the data redundancy. Conclusions A semantically integrated disease-associated database (SIDD) is developed, which integrates 18 disease-associated databases, for researchers to browse multiple types of DR-MPEs in a view. A web interface allows easy navigation for querying information through browsing a disease ontology tree or searching a disease term. Furthermore, a network visualization tool using Cytoscape Web plugin has been implemented in SIDD. It enhances the SIDD usage when viewing the relationships between diseases and DR-MPEs. The current version of SIDD (Jul 2013) documents 4,465,131 entries relating to 139,365 DR-MPEs, and to 3,824 human diseases. The database can be freely accessed from: http://mlg.hit.edu.cn/SIDD. PMID:24146757

Regulation of international energy markets: Economic effects of political actions

NASA Astrophysics Data System (ADS)

Shcherbakova, Anastasia V.

Recent increases in volatility of energy prices have led many governments to reevaluate their regard of national energy reserves and reconsider future exploration, production, and consumption patterns. The flurry of activity that has been generated by such price volatility has included large-scale nationalizations of energy sectors, unilateral renegotiations of foreign energy development contracts, and expropriations of resources from foreign energy firms on one hand, and on the other hand more rapid energy sector liberalization, intensified search for and development of renewable fuels and technologies, and development of incentives for increased energy efficiency and conservation. The aim of this dissertation is to examine and quantify the extent of positive and negative effects that have resulted from some of these activities. The first chapter focuses on quantifying the effect that nationalistic sentiment has had on economic attractiveness of energy sectors during the decade prior to the recent global economic crisis, as measured by foreign direct investment (FDI) inflows. Empirical results demonstrate that both political and economic conditions play an important role in investors' decisions. A combination of investment friendliness, corruption levels, and democracy all help to explain the trends in energy-sector investment levels over time in my sample countries, although differences in the types of corruption existing in these nations do not. Investment levels, in turn, appear to influence future levels of oil production, underscoring the significance of good investment policies for future success of energy sectors. Chapter two considers the response of energy stock prices to severe regulatory actions. It employs an event study framework to examine causal effects of critical informational announcements (i.e. events of expropriation and nationalization) on daily returns and cumulative losses in firm value of energy corporations. Results show that a firm's participation in a regulated market results in an average decline in its stock returns of up to 50 basis points per day, and a cumulative loss of more than 3.5% of its market value. Negative shocks to securities returns persist for at least two months. Participation in a regulated market, however, is not always unfavorable, as involved firms not directly targeted by regulatory action appear to gain sizable risk premiums. Additional evidence suggests that, although there is no direct linear relationship between firm size and effect magnitude, large firms tend to be hurt more in the short term, while small firms suffer bigger declines in returns over a longer time period. The last chapter turns to global electricity sectors to examine the development of Demand Response (DR) programs, which have become popular means of addressing the sector's central market failure of pricing below marginal generation cost. DR programs incorporate demand signals into retail electricity rates, and have the potential to effectively and inexpensively improve grid reliability and increase end-use efficiency. However, DR faces many challenges, arguably the most important of which is a general lack of information among consumers regarding usage levels and existence of alternative providers and rate plans. Financial considerations, lack of access to technological infrastructure, and misaligned producer incentives also play an important role in DR's limited success.

Timely and Needed Perspectives on Differential Response in Child Protective Services

ERIC Educational Resources Information Center

Ellett, Alberta J.

2013-01-01

This article is an invited commentary and analysis of the authors' completed systematic evaluation of Child Protective Services (CPS) differential response (DR) models. I write this commentary based on 25 years of public child welfare experience followed by 13 years as a social work professor and researcher. In their review of DR, the…

A Critical Appraisal of Issues in Differential Response: Moving the Field Forward

ERIC Educational Resources Information Center

Winokur, Marc A.; Gabel, George

2013-01-01

This reaction article highlights areas of agreement and disagreement with the study conducted by Hughes, Rycus, Saunders-Adams, Hughes, and Hughes on the current state of research and practice in differential response (DR). Overall, we agree with several of the arguments put forth by Hughes et al. regarding the limitations of DR research and the…

Novel topcoat materials with improved receding angles and dissolution properties for ArF immersion lithography

NASA Astrophysics Data System (ADS)

Yun, Sang Geun; Lee, Jin Young; Yang, Young Soo; Shin, Seung Wook; Lee, Sung Jae; Kwon, Hyo Young; Cho, Youn Jin; Choi, Seung Jib; Choi, Sang Jun; Kim, Jong Seob; Chang, Tuwon

2010-04-01

A topcoat material plays a significant role in achieving technology nodes below 45 nm via ArF immersion lithography. Switching the exposure medium between the lens and the photoresist (PR) film from gas (air, n=1) to liquid (H2O, n=1.44) may lead to leaching of the polymer, the photoacid generator (PAG), or the solvent. These substances can contaminate the lens or cause bubbles, which can lead to defects during the patterning. Previously reported topcoat materials mainly use hydrophobic fluoro-compounds and carboxylic acids to provide high dissolution rates (DR) to basic developers as well as high receding contact angles (RCA). Recently, the demand for a new top-coat material has risen since current materials cause water-mark defects and decreases in scan speeds, due to insufficient RCA's. However, RCA and DR are in a trade-off relationship as an increase in RCA generally results in a lower DR. To overcome this, a novel polymer with high-fluorine content was synthesized to produce a topcoat material with improved DR (120 nm/s in 2.38 wt% TMAH) and RCA (>70°). In addition, a strategy to control the pattern profile according to needs of customers was found.

IMF / World Bank boards of governors discuss population, migration.

PubMed

1994-05-01

A brief presentation was given of the statements Dr. Nafis Sadik, Executive Director of the UN Fund for Population Activities (UNFPA) and Secretary General of the 1994 International Conference on Population and Development (ICPD), made before a meeting of the International Monetary Fund (IMF) and the World Bank on resource flows to developing countries, population, international trade, and migration. The meeting was attended by finance ministers from 24 countries. The IMF Managing Director gave an overview at the meeting of the world economic situation and the need for international assistance for effective population and family planning programs. Dr. Sadik emphasized this need as a requirement for implementation of the 20-year ICPD Programme of Action. The increased investment was considered beneficial because it would increase life expectancy, lower demand for health and education services, reduce pressure in the job market, reduce economic hardship, and increase social stability. The growth of prosperity was considered by Dr. Sadik to be tied to increased demand for housing, energy, and utilities. A slower and more balanced population growth would allow for government services to meet demands and for the world to adjust to increasing numbers of people. Several ministers supported the call for increased funding of population programs and poverty reduction programs. A special communique by ministers recognized that the connections between economic growth, population, poverty reduction, health, investment in human resources, and environmental degradation must be integrated into population policy. Ministers urged the ICPD to emphasize improvements in primary school enrollment in low income countries, in access to family planning and health services, and in maternal and child mortality rates. Ministers wanted to see increases in the proportion of aid directed to population programs above the current 1.25%. Requests were made for more research into the social, political, and economic impact of international migration among both host and origin countries.

Making the Grid "Smart" Through "Smart" Microgrids: Real-Time Power Management of Microgrids with Multiple Distributed Generation Sources Using Intelligent Control

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

Nehrir, M. Hashem

In this Project we collaborated with two DOE National Laboratories, Pacific Northwest National Lab (PNNL) and Lawrence Berkeley National Lab (LBL). Dr. Hammerstrom of PNNL initially supported our project and was on the graduate committee of one of the Ph.D. students (graduated in 2014) who was supported by this project. He is also a committee member of a current graduate student of the PI who was supported by this project in the last two years (August 2014-July 2016). The graduate student is now supported be the Electrical and Computer Engineering (ECE) Department at Montana State University (MSU). Dr. Chris Marneymore » of LBL provided actual load data, and the software WEBOPT developed at LBL for microgrid (MG) design for our project. NEC-Labs America, a private industry, also supported our project, providing expert support and modest financial support. We also used the software “HOMER,” originally developed at the National Renewable Energy Laboratory (NREL) and the most recent version made available to us by HOMER Energy, Inc., for MG (hybrid energy system) unit sizing. We compared the findings from WebOpt and HOMER and designed appropriately sized hybrid systems for our case studies. The objective of the project was to investigate real-time power management strategies for MGs using intelligent control, considering maximum feasible energy sustainability, reliability and efficiency while, minimizing cost and undesired environmental impact (emissions). Through analytic and simulation studies, we evaluated the suitability of several heuristic and artificial-intelligence (AI)-based optimization techniques that had potential for real-time MG power management, including genetic algorithms (GA), ant colony optimization (ACO), particle swarm optimization (PSO), and multi-agent systems (MAS), which is based on the negotiation of smart software-based agents. We found that PSO and MAS, in particular, distributed MAS, were more efficient and better suited for our work. We investigated the following: • Intelligent load control - demand response (DR) - for frequency stabilization in islanded MGs (partially supported by PNNL). • The impact of high penetration of solar photovoltaic (PV)-generated power at the distribution level (partially supported by PNNL). • The application of AI approaches to renewable (wind, PV) power forecasting (proposed by the reviewers of our proposal). • Application of AI approaches and DR for real-time MG power management (partially supported by NEC Labs-America) • Application of DR in dealing with the variability of wind power • Real-time MG power management using DR and storage (partially supported by NEC Labs-America) • Application of DR in enhancing the performance of load-frequency controller • MAS-based whole-sale and retail power market design for smart grid A« less

Avenanthramide supplementation attenuates eccentric exercise-inflicted blood inflammatory markers in women.

PubMed

Koenig, Ryan T; Dickman, Jonathan R; Kang, Choung-Hun; Zhang, Tianou; Chu, Yi-Fang; Ji, Li Li

2016-01-01

Rigorous exercise is known to generate reactive oxygen species (ROS) and inflict inflammatory response. The present study investigated whether dietary supplementation of avenanthramides (AVA) in oats would increase antioxidant protection and reduce inflammation in humans after an acute bout of eccentric exercise. Young women (age 18-30 years, N = 16) were randomly divided into two groups in a double-blinded fashion, receiving two cookies made of oat flour providing 9.2 mg AVA (AVA) or 0.4 mg AVA (Control, C) each day for 8 weeks. Before and after the dietary regimen each group of subjects ran downhill (DR) on a treadmill at -9% grade for 1 h at a speed to elicit 75% of maximal heart rate. Blood samples were collected at rest, immediately and 24 h post-DR. Before dietary supplementation plasma creatine kinase activity and tumor necrosis factor (TNF)-α concentration were increased immediately after DR (P < 0.05), whereas neutrophil respiratory burst (NRB) was elevated 24 h post-DR (P < 0.05). CK and TNF-α response to DR was abolished during post-supplementation tests in both AVA and C groups, whereas NRB was blunted only in AVA but not in C. Plasma interleukin-6 level and mononuclear cell nuclear factor (NF) κB activity were not affected by DR either before or after dietary supplementation, but were lowered 24 h post-DR in AVA versus C (P < 0.05). Both groups increased plasma total antioxidant activity following 8-week dietary regimen (P < 0.05), whereas only AVA group increased resting plasma glutathione (GSH) concentration (P < 0.05), decreased glutathione disulfide response to DR, and lowered erythrocyte GSH peroxidase activity (P < 0.05). Our data of pre- and post-supplementation difference reflect an interaction between repeated measure effect of eccentric exercise and AVA in diet. Long-term AVA supplementation can attenuate blood inflammation markers, decrease ROS generation and NFkB activation, and increased antioxidant capacity during an eccentric exercise bout.

Death rattle: prevalence, prevention and treatment.

PubMed

Wildiers, Hans; Menten, Johan

2002-04-01

A retrospective analysis was performed to study the occurrence and treatment of death rattle (DR) in 107 consecutive dying patients on the palliative care unit of the University Hospital Leuven. The incidence of DR (23%) is lower than reported in literature, possibly due to low hydration. We found 2 types of rattle: "Real DR" responds generally very well to anticholinergic therapy, and is probably caused by non-expectorated secretions. "Pseudo DR" is poorly responsive to therapy and is probably caused by bronchial secretions due to pulmonary pathology, such as infection, tumor, fluid retention, or aspiration. Rattle disappeared in >90% for the patients with real DR. Real DR is a strong predictor for death, and 76% (19/25) died within 48h after onset. Administration of subcutaneous hyoscine hydrobromide, as a bolus or continuous infusion, is effective therapy for real DR and is comfortable for the patient and caregivers.

Multifocal electroretinography changes at the 1-year follow-up in a cohort of diabetic macular edema patients treated with ranibizumab.

PubMed

Baget-Bernaldiz, Marc; Romero-Aroca, Pedro; Bautista-Perez, Angel; Mercado, Joaquin

2017-10-01

To determine the changes in the multifocal electroretinogram (mfERG) at 1 year in a clinical series of diabetic macular edema (DME) patients treated with ranibizumab (RNBZ) using a pro re nata protocol. We analyzed a clinical series of 35 eyes of 35 patients with DME at baseline and after treating them with RNBZ over 1 year, in order to determine the change in the macular function, which was assessed by means of the response density and the implicit time of the first-order kernel (FOK) P1 wave of the mfERG at the foveola (R1), fovea (R2) and parafovea (R3). These electrophysiological parameters were studied taking into account different independent variables, such as DME type, degree of diabetic retinopathy (DR), level of preservation of both the ellipsoid zone (IS/OS) and the external limiting membrane (ELM) and changes in central retinal thickness (CRT) and total macular volume (TMV). We also studied the relationship between the response density and the best-corrected visual acuity (BCVA). Eyes with cystic and spongiform DME showed better response density with respect to the serous type (p < 0.001) at baseline. Similarly, eyes with high IS/OS and ELM preservation rates showed higher initial response density compared to the others (p < 0.001). Eyes with moderate DR had better response density compared to those with severe and proliferative DR (p = 0.001). At the beginning of the study, those eyes with proliferative and severe DR showed longer implicit times with respect to those with moderate DR (p = 0.04). The response density significantly increased in eyes that anatomically restored the IS/OS and the ELM after being treated with RNBZ (both p < 0.001). Similarly, eyes with spongiform DME further improved the response density with respect to those with cystic and serous DME (p < 0.001). On the contrary, eyes with hard exudates showed less improvement in their response density at the end of the study (p < 0.001). We observed a significant relationship between BCVA and the response density achieved at the end of the study (p = 0.012). Eyes with severe and proliferative DR significantly shortened implicit time compared to those with moderate DR (p = 0.04). The multifocal electroretinogram allowed us to differentiate groups of eyes with DME according to their electrophysiological profile, both initially and after being treated with RNBZ. Ranibizumab increased the response density in all DME types included in the study, with a maximum response in those eyes with spongiform type. Once treated with RNBZ, the macular electrophysiological activity improved in eyes that had a well-preserved ellipsoid zone and ELM. The presence of hard exudates was a limitation to the response density achieved at the foveola.

Retrieving clinically relevant diabetic retinopathy images using a multi-class multiple-instance framework

NASA Astrophysics Data System (ADS)

Chandakkar, Parag S.; Venkatesan, Ragav; Li, Baoxin

2013-02-01

Diabetic retinopathy (DR) is a vision-threatening complication from diabetes mellitus, a medical condition that is rising globally. Unfortunately, many patients are unaware of this complication because of absence of symptoms. Regular screening of DR is necessary to detect the condition for timely treatment. Content-based image retrieval, using archived and diagnosed fundus (retinal) camera DR images can improve screening efficiency of DR. This content-based image retrieval study focuses on two DR clinical findings, microaneurysm and neovascularization, which are clinical signs of non-proliferative and proliferative diabetic retinopathy. The authors propose a multi-class multiple-instance image retrieval framework which deploys a modified color correlogram and statistics of steerable Gaussian Filter responses, for retrieving clinically relevant images from a database of DR fundus image database.

Teacher Evaluation and Collective Bargaining: Resolving Policy at a Local Level

ERIC Educational Resources Information Center

Paige, Mark

2013-01-01

This case study analyzes controversial teacher evaluation policies in the context of collective bargaining. Dr. Jill Abrams, a new superintendent in a struggling school district, is at the center of the case. Her school board demands a form of teacher evaluation she finds problematic because it includes value-added modeling. Moreover, the board…

Stress in Professionals and Non-Professionals, Men and Women.

ERIC Educational Resources Information Center

Barko, Naomi

1983-01-01

Researchers are finding that high demands plus low control over how the job is done make a job stressful. According to Professor Robert Karasek of Columbia University, the statistics on heart disease and high blood pressure prove that nonprofessional workers such as typists are under more stress than professional workers such as teachers. Dr.…

Clinical Investigation Program, Reports Control Symbol MED-300(R1), Fiscal Year 1988

DTIC Science & Technology

1988-10-01

Dr. Venkataraman Balaraman, M.D. Department/Section: Clinical Investigation Key Words: arginine vasopressin (AVP); vascular smooth muscle responses...Kullama, Ph.D. Associate Investigators: Dr. Venkataraman Balaraman, M.D.; Dr. Kenneth T. Nakamura, M.D.; John R. Claybaugh, Ph.D. Department/Section...Harrison Hassell, MC Associate Investigators: John R. Claybaugh, Ph.D.; Arnold Siemsen, MD; Jon Streltzer, MD Department/Section: Medicine/ Nephrology

Ex vivo detection of adenovirus specific CD4{sup +} T-cell responses to HLA-DR-epitopes of the Hexon protein show a contracted specificity of T{sub HELPER} cells following stem cell transplantation

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

Serangeli, Celine; Bicanic, Oliver; Scheible, Michael H.

2010-02-20

Human adenovirus (HAdV) is a cause of significant morbidity and mortality in immunocompromised patients, especially after stem cell transplantation (SCT). Viral clearance has been attributed to CD4{sup +} T-cell responses against the Hexon-protein, but the frequency of specific T{sub HELPER} cells is extremely low or not detectable ex vivo and preference for different CD4{sup +} T-cell epitopes is variable among individuals. We therefore analyzed 44 healthy donors and 6 SCT-recipients for Hexon-specific CD4{sup +}-responses ex vivo, to identify epitopes which would be broadly applicable. We selected 19 candidate epitopes with predicted restriction to HLA-DR1/DR3/DR4/DR7; 16 were located within the highlymore » conserved regions, indicating cross-reactivity of T cells among HAdV-subspecies. Ten epitopes induced CD4{sup +}-proliferation in >50% of individuals, confirmed by intracellular IFN-gamma detection. Three SCT recipients who recovered from an infection with HAdV displayed reactivity towards only a single hexon epitope, whereas healthy individuals were responsive to two to eight epitopes (median 3). The ex vivo detection of Hexon-specific CD4{sup +} T-cells, without any long-term culture in vitro, enables the detection and generation of HAdV-specific CD4{sup +} T cells for adoptive T-cell transfer against HAdV-infection post SCT.« less

Motherhood and infant contact regulate neuroplasticity in the serotonergic midbrain dorsal raphe.

PubMed

Holschbach, M Allie; Lonstein, Joseph S

2017-02-01

The adult brain shows remarkable neuroplasticity in response to hormones and the socioemotional modifications that they influence. In females with reproductive and maternal experience, this neuroplasticity includes the birth and death of cells in several forebrain regions involved in maternal caregiving and postpartum affective state. Such plasticity in midbrain sites critical for these behavioral and emotional processes has never been examined, though. By visualizing bromodeoxyuridine (BrdU) to label mitotic cells, NeuroD for neuronal precursors, and TUNEL to identify dying cells, we found that the midbrain dorsal raphe nucleus (DR, the source of most ascending serotoninergic projections) exhibited significant neuroplasticity in response to motherhood. Specifically, BrdU analyses revealed that DR newborn cell survival (but not proliferation) was regulated by reproductive state, such that cells born early postpartum were less likely to survive 12 days to reach the late postpartum period compared to cells born during late pregnancy that survived 12 days to reach the early postpartum period. Many of the surviving cells in the DR were NeuN immunoreactive, suggesting a neuronal phenotype. Consistent with these findings, late postpartum rats had fewer NeuroD-immunoreactive DR cells than early postpartum rats. Maternal experience contributed to the late postpartum reduction in DR newborn cell survival because removing the litter at parturition increased cell survival as well as reduced cell death. Unlike cytogenesis in the maternal hippocampus, which is reduced by circulating glucocorticoids, DR newborn cell survival was unaffected by postpartum adrenalectomy. These effects of reproductive state and motherhood on DR plasticity were associated with concurrent changes in DR levels of serotonin's precursor, 5-HTP, and its metabolite, 5-HIAA. Our results demonstrate for the first time that cytogenesis occurs in the midbrain DR of any adult mammal, that DR plasticity is influenced by female reproductive state and maternal experience, and that this plasticity is accompanied by changes in DR serotonergic function. Because serotonin is critical for postpartum caregiving behaviors and maternal affective state, plasticity in the DR may contribute to the neurochemical changes necessary for successful motherhood. Copyright © 2016 Elsevier Ltd. All rights reserved.

Genome-Wide Distribution, Organisation and Functional Characterization of Disease Resistance and Defence Response Genes across Rice Species

PubMed Central

Singh, Sangeeta; Chand, Suresh; Singh, N. K.; Sharma, Tilak Raj

2015-01-01

The resistance (R) genes and defense response (DR) genes have become very important resources for the development of disease resistant cultivars. In the present investigation, genome-wide identification, expression, phylogenetic and synteny analysis was done for R and DR-genes across three species of rice viz: Oryza sativa ssp indica cv 93-11, Oryza sativa ssp japonica and wild rice species, Oryza brachyantha. We used the in silico approach to identify and map 786 R -genes and 167 DR-genes, 672 R-genes and 142 DR-genes, 251 R-genes and 86 DR-genes in the japonica, indica and O. brachyanth a genomes, respectively. Our analysis showed that 60.5% and 55.6% of the R-genes are tandemly repeated within clusters and distributed over all the rice chromosomes in indica and japonica genomes, respectively. The phylogenetic analysis along with motif distribution shows high degree of conservation of R- and DR-genes in clusters. In silico expression analysis of R-genes and DR-genes showed more than 85% were expressed genes showing corresponding EST matches in the databases. This study gave special emphasis on mechanisms of gene evolution and duplication for R and DR genes across species. Analysis of paralogs across rice species indicated 17% and 4.38% R-genes, 29% and 11.63% DR-genes duplication in indica and Oryza brachyantha, as compared to 20% and 26% duplication of R-genes and DR-genes in japonica respectively. We found that during the course of duplication only 9.5% of R- and DR-genes changed their function and rest of the genes have maintained their identity. Syntenic relationship across three genomes inferred that more orthology is shared between indica and japonica genomes as compared to brachyantha genome. Genome wide identification of R-genes and DR-genes in the rice genome will help in allele mining and functional validation of these genes, and to understand molecular mechanism of disease resistance and their evolution in rice and related species. PMID:25902056

Around Marshall

NASA Image and Video Library

1996-03-15

Portrait of Marshall's eighth Center Director Dr. Jerroll W. Littles (1996-1998). During the two short years as Center Director, Dr. Littles' administration was responsible for the space lab mission, the space science projects, alternative light-weight launch vehicles and their engine development.

[The role of Turkish physicians in the vaccination against typhus during the years of World War I].

PubMed

Karatepe, Mustafa

2008-04-01

During the years of World War I, several severe typhus epidemics were seen in Erzurum and nearby cities. A total of 164 health officers, 125 of whom were physicians, struggled against the epidemic in the region but also they lost their lives due to typhus. Vaccination against typhus was one of the means of fighting the epidemic. However, there were some claims that a small group of Turkish physicians injected typhus-contaminated serum into Armenian civilians during World War I, and that this should be accepted as a form of biological warfare against Armenian civilians. The purpose of this article is to set out how, by whom, and on whom, and under what conditions the typhus vaccination was applied in order to reveal the truth in terms of the evidence found in historical documents. The typhus vaccine was prepared from blood taken from febrile patients affected by the disease. After the blood of the patients were defibrinated and inactivated at 60 degrees C for an hour, it was used. As the amount of blood needed to prepare the vaccine was so great, the amount of available vaccine was always insufficient to meet the demand. Hence, the prepared vaccine was only applied to those which had the higher risk of contracting typhus such as physicians and nurses. The vaccine prepared by The Third Army Health Commander Dr. Tevfik Salim was first applied to nine officers, five of whom were physicians, and among whom were Dr. Haydar Cemal and Dr. Salahattin on March 28, 1915 in Hasankale, Erzurum. Furthermore, the same vaccine was applied to people in the vicinity by Dr. Alaattin in Erzurum, Dr. Abdulhalim Asim in Bayburt, Dr. Izak in Sivas and Dr. Mihran in Hasankale. Ali Ihsan Sabis and Fevzi Cakmak, who were high ranking officers, were among those who volunteered to have the vaccination. The Third Army Health Commander Dr. Tevfik Salim ordered that the vaccine should not be applied without blood inactivation. Despite this order, Dr. Hamit Osman, who had a mental illness, applied the vaccination without inactivating the blood to some people. Among those were physicians of the Red Crescent Hospital together with soldiers who were nursing in the hospitals in Erzincan. Dr. Hamdi Suat inactivated the blood by leaving it at -16 degrees C for 24-48 hours, and instead of giving a single dose, he applied three-doses with 3-day-intervals, followed by a one more dose, which he called "the vaccine for absolute immunization" to the same people after 10-23 days. This "vaccine for absolute immunization" was actually typhus-contaminated blood which had not been inactivated. It should be noted that he injected himself with the same form of vaccine. In his article published in German in 1916 and in Turkish in 1917, he stated that he injected "the vaccine for absolute immunization" to some subjects 'condemned to death'. Dr. Haydar Cemal claimed, in a newspaper dated December 23, 1918, that the people reported as subjects 'condemned to death' were indeed Armenians, and that the innocent Armenians marked out for deportation were inoculated with the blood of typhus fever patients, and that he eyewitnessed all these events. As a result of his claims, the Interior Ministry demanded an immediate investigation, and at the end of that investigation it was understood that Dr. Haydar Cemal and Dr. Hamdi Suat had never worked together in Erzincan at the time Dr. Haydar Cemal claimed. All the claims were refuted by the investigating committee and nobody was charged. During a severe typhus epidemic, Turkish physicians injected the typhus vaccine for the purpose of "saving a life from the fire". The typhus vaccine was prepared using the available scientific knowledge of the time. No racial or religious discrimination against the people vaccinated had been proved. According to the sources, the claim that some Turkish physicians used the blood of patients with typhus as a means of biological warfare does not reflect the historical truth.

Pre-Operative Diet Impacts the Adipose Tissue Response to Surgical Trauma

PubMed Central

Nguyen, Binh; Tao, Ming; Yu, Peng; Mauro, Christine; Seidman, Michael A.; Wang, Yaoyu E.; Mitchell, James; Ozaki, C. Keith

2012-01-01

Background Short-term changes in pre-operative nutrition can have profound effects on surgery related outcomes such as ischemia reperfusions injury in pre-clinical models. Dietary interventions that lend protection against stress in animal models (e.g. fasting, dietary restriction [DR]) impact adipose tissue quality/quantity. Adipose tissue holds high surgical relevance due to its anatomic location and high tissue volume, and it is ubiquitously traumatized during surgery. Yet the response of adipose tissue to trauma under clinically relevant circumstances including dietary status remains poorly defined. We hypothesized that pre-operative diet alters the adipose tissue response to surgical trauma. Methods A novel mouse model of adipose tissue surgical trauma was employed. Dietary conditions (diet induced obesity [DIO], pre-operative DR) were modulated prior to application of surgical adipose tissue trauma in the context of clinically common scenarios (different ages, simulated bacterial wound contamination). Local/distant adipose tissue phenotypic responses were measured as represented by gene expression of inflammatory, tissue remodeling/growth, and metabolic markers. Results Surgical trauma had a profound effect on adipose tissue phenotype at the site of trauma. Milder but significant distal effects on non-traumatized adipose tissue were also observed. DIO exacerbated the inflammatory aspects of this response, and pre-operative DR tended to reverse these changes. Age and LPS-simulated bacterial contamination also impacted the adipose tissue response to trauma, with young adult animals and LPS treatment exacerbating the proinflammatory response. Conclusions Surgical trauma dramatically impacts both local and distal adipose tissue biology. Short-term pre-operative DR may offer a strategy to attenuate this response. PMID:23274098

Impacts of Using Distributed Energy Resources to Reduce Peak Loads in Vermont

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

Ruth, Mark F.; Lunacek, Monte S.; Jones, Birk

To help the United States develop a modern electricity grid that provides reliable power from multiple resources as well as resiliency under extreme conditions, the U.S. Department of Energy (DOE) is leading the Grid Modernization Initiative (GMI) to help shape the future of the nation's grid. Under the GMI, DOE funded the Vermont Regional Initiative project to provide the technical support and analysis to utilities that need to mitigate possible impacts of increasing renewable generation required by statewide goals. Advanced control of distributed energy resources (DER) can both support higher penetrations of renewable energy by balancing controllable loads to windmore » and photovoltaic (PV) solar generation and reduce peak demand by shedding noncritical loads. This work focuses on the latter. This document reports on an experiment that evaluated and quantified the potential benefits and impacts of reducing the peak load through demand response (DR) using centrally controllable electric water heaters (EWHs) and batteries on two Green Mountain Power (GMP) feeders. The experiment simulated various hypothetical scenarios that varied the number of controllable EWHs, the amount of distributed PV systems, and the number of distributed residential batteries. The control schemes were designed with several objectives. For the first objective, the primary simulations focused on reducing the load during the independent system operator (ISO) peak when capacity charges were the primary concern. The second objective was to mitigate DR rebound to avoid new peak loads and high ramp rates. The final objective was to minimize customers' discomfort, which is defined by the lack of hot water when it is needed. We performed the simulations using the National Renewable Energy Laboratory's (NREL's) Integrated Energy System Model (IESM) because it can simulate both electric power distribution feeder and appliance end use performance and it includes the ability to simulate multiple control strategies.« less

The correlation between preoperative volumetry and real graft weight: comparison of two volumetry programs.

PubMed

Mussin, Nadiar; Sumo, Marco; Lee, Kwang-Woong; Choi, YoungRok; Choi, Jin Yong; Ahn, Sung-Woo; Yoon, Kyung Chul; Kim, Hyo-Sin; Hong, Suk Kyun; Yi, Nam-Joon; Suh, Kyung-Suk

2017-04-01

Liver volumetry is a vital component in living donor liver transplantation to determine an adequate graft volume that meets the metabolic demands of the recipient and at the same time ensures donor safety. Most institutions use preoperative contrast-enhanced CT image-based software programs to estimate graft volume. The objective of this study was to evaluate the accuracy of 2 liver volumetry programs (Rapidia vs . Dr. Liver) in preoperative right liver graft estimation compared with real graft weight. Data from 215 consecutive right lobe living donors between October 2013 and August 2015 were retrospectively reviewed. One hundred seven patients were enrolled in Rapidia group and 108 patients were included in the Dr. Liver group. Estimated graft volumes generated by both software programs were compared with real graft weight measured during surgery, and further classified into minimal difference (≤15%) and big difference (>15%). Correlation coefficients and degree of difference were determined. Linear regressions were calculated and results depicted as scatterplots. Minimal difference was observed in 69.4% of cases from Dr. Liver group and big difference was seen in 44.9% of cases from Rapidia group (P = 0.035). Linear regression analysis showed positive correlation in both groups (P < 0.01). However, the correlation coefficient was better for the Dr. Liver group (R 2 = 0.719), than for the Rapidia group (R 2 = 0.688). Dr. Liver can accurately predict right liver graft size better and faster than Rapidia, and can facilitate preoperative planning in living donor liver transplantation.

Mutual Regulation of NOD2 and RIG-I in Zebrafish Provides Insights into the Coordination between Innate Antibacterial and Antiviral Signaling Pathways.

PubMed

Nie, Li; Xu, Xiao-Xiao; Xiang, Li-Xin; Shao, Jian-Zhong; Chen, Jiong

2017-05-27

Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) and retinoic acid-inducible gene I (RIG-I) are two important cytosolic pattern recognition receptors (PRRs) in the recognition of pathogen-associated molecular patterns (PAMPs), initiating innate antibacterial and antiviral signaling pathways. However, the relationship between these PRRs, especially in teleost fish models, is rarely reported. In this article, we describe the mutual regulation of zebrafish NOD2 ( Dr NOD2) and RIG-I ( Dr RIG-I) in innate immune responses. Luciferase assays were conducted to determine the activation of NF-κB and interferon signaling. Morpholino-mediated knockdown and mRNA-mediated rescue were performed to further confirm the regulatory roles between Dr NOD2 and Dr RIG-I. Results showed that Dr NOD2 and Dr RIG-I shared conserved structural hallmarks with their mammalian counterparts, and activated Dr RIG-I signaling can induce Dr NOD2 production. Surprisingly, Dr NOD2-initiated signaling can also induce Dr RIG-I expression, indicating that a mutual regulatory mechanism may exist between them. Studies conducted using HEK293T cells and zebrafish embryos showed that Dr RIG-I could negatively regulate Dr NOD2-activated NF-κB signaling, and Dr NOD2 could inhibit Dr RIG-I-induced IFN signaling. Moreover, knocking down Dr RIG-I expression by morpholino could enhance Dr NOD2-initiated NF-κB activation, and vice versa, which could be rescued by their corresponding mRNAs. Results revealed a mutual feedback regulatory mechanism underlying NOD2 and RIG-I signaling pathways in teleosts. This mechanism reflects the coordination between cytosolic antibacterial and antiviral PRRs in the complex network of innate immunity.

Latin America multidisciplinary research on heat shock proteins and cell stress: proceedings of the first conference of the Latin America Chapter of the Cell Stress Society International.

PubMed

Bausero, María A

2015-09-01

The First Conference of the Latin America Chapter of the Cell Stress Society International (CSSI) organized by CSSI was held in Montevideo, Uruguay, on March 11-14, 2014. The Latin America Chapter of the CSSI (LAC-CSSI) was established at the Workshop on the Molecular Biology of the Stress Response, Porto Alegre, Brazil, May 2012. The chapter's first meeting took place in the beautiful city of Montevideo and was chaired by the first (LAC-CSSI) elected president Professor María Bausero. Forty-two invited speakers presented their work to more than 100 scientists. The first day of the conference was dedicated to an introductory program for students, young investigators, and participants new to the field of molecular chaperones and the stress response. These seminars were held in the Pasteur Institute of Montevideo and the Faculty of Sciences of the University of the Republic. These institutions were carefully selected to give foreign participants a broad view of the diversity of students and institutions doing research in Uruguay, as well as an opportunity for direct interaction with our scientists and students. Invited speakers for the seminar series were Dr. Wolfgang Schumann, Dr. Cristina Bonorino, Dr. Antonio De Maio, Dr. Ian Brown, Dr. Rafael Radi, Dr. Daniel Ciocca, and Dr. Celia Quijano. The remaining days of the conference took place at the Sheraton Hotel in Montevideo, and the scientific sessions are discussed below.

A Case of Uveal Colobomas Showing Marked Left-Right Difference in Diabetic Retinopathy.

PubMed

Moriya, Takeshi; Ochi, Ryosuke; Imagawa, Yukihiro; Sato, Bumpei; Morishita, Seita; Tonari, Masahiro; Fukumoto, Masanori; Suzuki, Hiroyuki; Kobayashi, Takatoshi; Kida, Teruyo; Ikeda, Tsunehiko

2016-01-01

Congenital uveal colobomas, including inferior iris and choroidal colobomas, are associated with microcornea and microphthalmia and often show left-right differences (laterality). The purpose of this study was to report a case of choroidal coloboma associated with left-right differences in diabetic retinopathy (DR). This study reports a 59-year-old male with bilateral iris and choroidal colobomas. The colobomatous area in the patient's right eye extended to the macula, and his right eye had been amblyopic since birth. The colobomatous area in his left eye was less extensive and did not involve the macula. Examination of the patient's left eye revealed multiple hemorrhages and hard exudates in the macula due to DR, but examination of his right eye showed almost no changes in DR, thus revealing a marked left-right difference. Optical coherence tomography showed more extensive retinal thinning in the patient's right eye than in his left eye. Fluorescein fundus angiography revealed a retinal nonperfusion area only in the left eye, and panretinal photocoagulation was subsequently performed. Our findings show that the reason for the left-right difference in DR was attributed to the more severe choroidal coloboma and retinal thinning in the patient's right eye compared to his left eye, thus reducing oxygen demand, as is also seen in eyes with severe myopia.

Womanpower Policies for the 1970's. Seminar on Manpower Policy and Program (Washington, D.C., April 13, 1967).

ERIC Educational Resources Information Center

Cohen, Wilbur J.

One of a series of proceedings of seminars on Manpower Policy and Program, this report presents a condensed transcript of a seminar. Dr. Wilbur J. Cohen discussed women in the labor force today, future trends in women's employment, future demands for workers, health personnel shortages, educational opportunities, homemaker services needed, and…

A framework for analyzing the cognitive complexity of computer-assisted clinical ordering.

PubMed

Horsky, Jan; Kaufman, David R; Oppenheim, Michael I; Patel, Vimla L

2003-01-01

Computer-assisted provider order entry is a technology that is designed to expedite medical ordering and to reduce the frequency of preventable errors. This paper presents a multifaceted cognitive methodology for the characterization of cognitive demands of a medical information system. Our investigation was informed by the distributed resources (DR) model, a novel approach designed to describe the dimensions of user interfaces that introduce unnecessary cognitive complexity. This method evaluates the relative distribution of external (system) and internal (user) representations embodied in system interaction. We conducted an expert walkthrough evaluation of a commercial order entry system, followed by a simulated clinical ordering task performed by seven clinicians. The DR model was employed to explain variation in user performance and to characterize the relationship of resource distribution and ordering errors. The analysis revealed that the configuration of resources in this ordering application placed unnecessarily heavy cognitive demands on the user, especially on those who lacked a robust conceptual model of the system. The resources model also provided some insight into clinicians' interactive strategies and patterns of associated errors. Implications for user training and interface design based on the principles of human-computer interaction in the medical domain are discussed.

The origins of the modern pain clinic at the Mayo Clinic.

PubMed

Weingarten, Toby N; Martin, David P; Bacon, Douglas R

2011-07-01

In the 1970s the practice of pain management evolved from the isolated anesthesiologist practicing pain "on the side" to a multi-disciplinary model. The impetus behind this change remains obscure. To understand how this national trend occurred locally and to examine national institutional challenges which should be reflected at the Mayo Clinic that stimulated the establishment of a modern academic pain practice, we interviewed appropriate staff members and reviewed relevant departmental meeting notes. Following the 1959 departure of Dr. John Lundy from Mayo, Dr. Robert Jones became the primary practitioner of pain procedures in addition to his anesthesiology practice. In 1973, close to his retirement, Jones wrote a letter to the department chairman, Dr. Richard Theye, expressing frustration because this divided practice hindered patient care, education, and research opportunities. In 1974 Dr. Lee Nauss joined Mayo upon residency completion at Virginia Mason where he received training in regional anesthesia and met Dr. John Bonica. Nauss introduced epidural steroid injections, which became in such great demand that other anesthesiologists needed to cover his rooms. Within two months, Theye asked Nauss to create a stand-alone pain clinic. Nauss recruited Dr. Tony Wang and opened the clinic that year. This pain clinic increased patient access, improved resident education, allowed for the establishment of a fellowship program, and produced ground-breaking research (e.g., the human administration of intrathecal morphine). The establishment of the pain clinic addressed the deficiencies of a mixed pain and anesthesia practice. The pain specialist could now focus attention on and provide better access for pain patients, keep current with clinical practice, engage in research, and educate future pain specialists.

Toxic shock syndrome: characterization of human immune responses to TSST-1 and evidence for sensitivity thresholds.

PubMed

Kimber, Ian; Nookala, Suba; Davis, Catherine C; Gerberick, G Frank; Tucker, Heidi; Foertsch, Leslie M; Dearman, Rebecca J; Parsonnet, Jeffrey; Goering, Richard V; Modern, Paul; Donnellen, Meghan; Morel, Jorge; Kotb, Malak

2013-07-01

Noninvasive vaginal infections by Staphylococcus aureus strains producing the superantigen TSST-1 can cause menstrual toxic shock syndrome (mTSS). With the objective of exploring the basis for differential susceptibility to mTSS, the relative responsiveness to TSST-1 of healthy women has been investigated. Peripheral blood mononuclear cells from healthy donors were incubated with purified TSST-1 or with the T-cell mitogen phytohemmaglutinin (PHA), and proliferation was measured. The concentrations of TSST-1 and PHA required to elicit a response equivalent to 15% of the maximal achievable response (EC15) were determined. Although with PHA, EC15 values were comparable between donors, subjects could be classified as being of high, medium, or low sensitivity based on responsiveness to TSST-1. Sensitivity to TSST-1-induced proliferation was associated with increased production of the cytokines interleukin-2 and interferon-γ. When the entire T lymphocyte population was considered, there were no differences between sensitivity groups with respect to the frequency of cells known to be responsive to TSST-1 (those bearing CD3(+) Vβ2(+)). However, there was an association between sensitivity to TSST-1 and certain HLA-class II haplotypes. Thus, the frequencies of DR7DQ2, DR14DQ5, DR4DQ8, and DR8DQ4 haplotypes were greater among those with high sensitivity, a finding confirmed by analysis of responses to immortalized homozygous B cell lines. Collectively, the results reveal that factors other than neutralizing antibody and the frequency of Vβ2(+) T lymphocytes determine immunological responsiveness to TSST-1. Differential responsiveness of lymphocytes to TSST-1 may form the basis of interindividual variations in susceptibility to mTSS.

Preserving genome integrity: the DdrA protein of Deinococcus radiodurans R1.

PubMed

Harris, Dennis R; Tanaka, Masashi; Saveliev, Sergei V; Jolivet, Edmond; Earl, Ashlee M; Cox, Michael M; Battista, John R

2004-10-01

The bacterium Deinococcus radiodurans can withstand extraordinary levels of ionizing radiation, reflecting an equally extraordinary capacity for DNA repair. The hypothetical gene product DR0423 has been implicated in the recovery of this organism from DNA damage, indicating that this protein is a novel component of the D. radiodurans DNA repair system. DR0423 is a homologue of the eukaryotic Rad52 protein. Following exposure to ionizing radiation, DR0423 expression is induced relative to an untreated control, and strains carrying a deletion of the DR0423 gene exhibit increased sensitivity to ionizing radiation. When recovering from ionizing-radiation-induced DNA damage in the absence of nutrients, wild-type D. radiodurans reassembles its genome while the mutant lacking DR0423 function does not. In vitro, the purified DR0423 protein binds to single-stranded DNA with an apparent affinity for 3' ends, and protects those ends from nuclease degradation. We propose that DR0423 is part of a DNA end-protection system that helps to preserve genome integrity following exposure to ionizing radiation. We designate the DR0423 protein as DNA damage response A protein.

Evaluation of the Maxillary Dental Midline Relative to the Face

DTIC Science & Technology

2008-06-01

at Chapel Hill in partial fulfillment of the requirements for the degree of Master of Science in the School of Dentistry ( Orthodontics ). Chapel Hill...2008 Approved by: Dr. Ceib Phillips Dr. H. Garland Hershey Dr. Harald 0. Heymann 20080630 214 REPORT DOCUMENTATION PAGE Form Approved I_ OMB No. 0704...0188 The public reporting burden for this collection of information is estimated to average 1 hour per response, including the time for reviewing

Health effects of fine particulate air pollution: lines that connect

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

Judith C. Chow; John G. Watson; Joe L. Mauderly

2006-10-15

In the 2006 A&WMA Critical Review on 'Health Effects of fine particulate air pollution: lines that connect' Drs. C. Arden Pope III and Douglas Dockery addressed the epidemiological evidence for the effects of particulate matter (PM) on human health indicators. The review documents substantial progress since the 1997 Critical Review in the areas of: (1) short-term exposure and mortality; (2) long-term exposure and mortality; (3) time scales of exposure; (4) the shape of the concentration-response function; (5) cardiovascular disease; and (6) biological plausibility. This critical review discussion was compiled from written submissions and presentation transcripts, which were revised for concisenessmore » and to minimize redundancy. The invited discussants were as follows were: Dr. Joe L. Mauderly, Dr. Daniel L. Costa, Dr. Ronald E. Wyzga, and Dr. Sverre Vedal. The contributing discussants were: Dr. George M. Hidy, Sam L. Altshuler, Dr. David Marrack, Jon M. Heuss, and Dr. George T. Wolff. See Coal Abstracts entry Sep 2006 00390 for the Critical Review. 80 refs.« less

Association of Systemic Inflammatory and Anti-inflammatory Responses with Adverse Outcomes in Acute Pancreatitis: Preliminary Results of an Ongoing Study.

PubMed

Sharma, Deepesh; Jakkampudi, Aparna; Reddy, Ratnakar; Reddy, Panyala Balakumar; Patil, Aasish; Murthy, H V V; Rao, G Venkat; Reddy, D Nageshwar; Talukdar, Rupjyoti

2017-12-01

This paper reports preliminary data of an ongoing study that evaluates the association of systemic inflammatory response (SIRS) with early severe acute pancreatitis (ESAP) and compensatory anti-inflammatory response syndrome (characterized by HLA-DR down-regulation) with infected pancreatic necrosis (IPN). Consecutive patients presenting within 72 h of symptom onset with organ dysfunction and/or local complications were included. Following parameters were recorded: demographics, etiology, SIRS, APACHE II, creatinine, BUN. Circulating IL-8, IL-6, IL-10, TNF-alpha concentrations and expression of HLA-DR and IL-10 by qRT-PCR in PBMCs were measured. Strength of associations of cytokine concentration and HLA-DR/IL-10 expression with outcomes was expressed as Hedges' G and relative risk (95% CI). Twenty-eight patients (10 MSAP; 18 SAP) fulfilled inclusion criteria. Twelve patients had ESAP and eight presented with organ failure. Admission SIRS worsened in eight (28.6%) patients over 48 h. Sixteen (57.1%) patients developed primary IPN. Twenty-one (75%) patients had HLA-DR down-regulation during the first week, which persisted to the second week in 12 (42.9%) patients. IL-8, IL-6, and TNF-α progressively increased from healthy controls to MAP to MSAP to SAP. IL-6 and TNF-α was higher in the patients who developed ESAP (p = 0.01 and 0.05, respectively). Patients who died within the first week also had a significantly elevated concentration of IL-6 and TNF-α (p = 0.02 and 0.01, respectively). The relative risk (95% CI) of developing primary IPN with persistent HLA-DR down-regulation till the second week of illness was 11.3 (1.6-82.4; p = 0.01). Our study objectively demonstrates significant association of ESAP and early mortality with primary cytokine response, and development of IPN with persistent HLA-DR down-regulation.

Systems modeling accurately predicts responses to genotoxic agents and their synergism with BCL-2 inhibitors in triple negative breast cancer cells.

PubMed

Lucantoni, Federico; Lindner, Andreas U; O'Donovan, Norma; Düssmann, Heiko; Prehn, Jochen H M

2018-01-19

Triple negative breast cancer (TNBC) is an aggressive form of breast cancer which accounts for 15-20% of this disease and is currently treated with genotoxic chemotherapy. The BCL2 (B-cell lymphoma 2) family of proteins controls the process of mitochondrial outer membrane permeabilization (MOMP), which is required for the activation of the mitochondrial apoptosis pathway in response to genotoxic agents. We previously developed a deterministic systems model of BCL2 protein interactions, DR_MOMP that calculates the sensitivity of cells to undergo mitochondrial apoptosis. Here we determined whether DR_MOMP predicts responses of TNBC cells to genotoxic agents and the re-sensitization of resistant cells by BCL2 inhibitors. Using absolute protein levels of BAX, BAK, BCL2, BCL(X)L and MCL1 as input for DR_MOMP, we found a strong correlation between model predictions and responses of a panel of TNBC cells to 24 and 48 h cisplatin (R 2  = 0.96 and 0.95, respectively) and paclitaxel treatments (R 2  = 0.94 and 0.95, respectively). This outperformed single protein correlations (best performer BCL(X)L with R 2 of 0.69 and 0.50 for cisplatin and paclitaxel treatments, respectively) and BCL2 proteins ratio (R 2 of 0.50 for cisplatin and 0.49 for paclitaxel). Next we performed synergy studies using the BCL2 selective antagonist Venetoclax /ABT199, the BCL(X)L selective antagonist WEHI-539, or the MCL1 selective antagonist A-1210477 in combination with cisplatin. In silico predictions by DR_MOMP revealed substantial differences in treatment responses of BCL(X)L, BCL2 or MCL1 inhibitors combinations with cisplatin that were successfully validated in cell lines. Our findings provide evidence that DR_MOMP predicts responses of TNBC cells to genotoxic therapy, and can aid in the choice of the optimal BCL2 protein antagonist for combination treatments of resistant cells.

A PerR-like protein involved in response to oxidative stress in the extreme bacterium Deinococcus radiodurans

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

Liu, Chengzhi; Wang, Liangyan; Li, Tao

2014-07-18

Highlights: • We report a novel PerR-like protein of Fur family in D. radiodurans that is not annotated in the current database. • drperR responses to H{sub 2}O{sub 2} and functions as a negative regulator of katE and dps. • We provided implications on how to utilize sequenced genome data and the importance of genome data mining. • This study adds knowledge to complicated regulatory network that responds to ROS stress in D. radiodurans. - Abstract: Response and defense systems against reactive oxygen species (ROS) contribute to the remarkable resistance of Deinococcus radiodurans to oxidative stress induced by oxidants ormore » radiation. However, mechanisms involved in ROS response and defense systems of D. radiodurans are not well understood. Fur family proteins are important in ROS response. Only a single Fur homolog is predicted by sequence similarity in the current D. radiodurans genome database. Our bioinformatics analysis demonstrated an additional guanine nucleotide in the genome of D. radiodurans that is not in the database, leading to the discovery of another Fur homolog DrPerR. Gene disruption mutant of DrPerR showed enhanced resistance to hydrogen peroxide (H{sub 2}O{sub 2}) and increased catalase activity in cell extracts. Real-time PCR results indicated that DrPerR functions as a repressor of the catalase gene katE. Meanwhile, derepression of dps (DNA-binding proteins from starved cells) gene under H{sub 2}O{sub 2} stress by DrPerR point to its regulatory role in metal ions hemostasis. Thus, DrPerR might function as a Fur homolog protein which is involved in ROS response and defense. These results help clarify the complicated regulatory network that responds to ROS stress in D. radiodurans.« less

Evolutionary Diagnosis of non-synonymous variants involved in differential drug response

PubMed Central

2015-01-01

Background Many pharmaceutical drugs are known to be ineffective or have negative side effects in a substantial proportion of patients. Genomic advances are revealing that some non-synonymous single nucleotide variants (nsSNVs) may cause differences in drug efficacy and side effects. Therefore, it is desirable to evaluate nsSNVs of interest in their ability to modulate the drug response. Results We found that the available data on the link between drug response and nsSNV is rather modest. There were only 31 distinct drug response-altering (DR-altering) and 43 distinct drug response-neutral (DR-neutral) nsSNVs in the whole Pharmacogenomics Knowledge Base (PharmGKB). However, even with this modest dataset, it was clear that existing bioinformatics tools have difficulties in correctly predicting the known DR-altering and DR-neutral nsSNVs. They exhibited an overall accuracy of less than 50%, which was not better than random diagnosis. We found that the underlying problem is the markedly different evolutionary properties between positions harboring nsSNVs linked to drug responses and those observed for inherited diseases. To solve this problem, we developed a new diagnosis method, Drug-EvoD, which was trained on the evolutionary properties of nsSNVs associated with drug responses in a sparse learning framework. Drug-EvoD achieves a TPR of 84% and a TNR of 53%, with a balanced accuracy of 69%, which improves upon other methods significantly. Conclusions The new tool will enable researchers to computationally identify nsSNVs that may affect drug responses. However, much larger training and testing datasets are needed to develop more reliable and accurate tools. PMID:25952014

Differential effects of exposure to low-light or high-light open-field on anxiety-related behaviors; relationship to c-Fos expression in serotonergic and non-serotonergic neurons in the dorsal raphe nucleus

PubMed Central

Bouwknecht, J. Adriaan; Spiga, Francesca; Staub, Daniel R.; Hale, Matthew W.; Shekhar, Anantha; Lowry, Christopher A.

2007-01-01

Serotonergic systems arising from the mid-rostrocaudal and caudal dorsal raphe nucleus (DR) have been implicated in the facilitation of anxiety-related behavioral responses by anxiogenic drugs or aversive stimuli. In this study we attempted to determine a threshold to engage serotonergic neurons in the DR following exposure to aversive conditions in an anxiety-related behavioral test. We manipulated the intensity of anxiogenic stimuli in studies of male Wistar rats by leaving them undisturbed (CO), briefly handling them (HA), or exposing them to an open-field arena for 15-min under low-light (LL: 8-13 lux) or high-light (HL: 400-500 lux) conditions. Rats exposed to HL conditions responded with reduced locomotor activity, reduced time spent exploring the center of the arena, a lower frequency of rearing and grooming, and an increased frequency of facing the corner of the arena compared to LL rats. Rats exposed to HL conditions had small but significant increases in c-Fos expression within serotonergic neurons in subdivisions of the rostral DR. Exposure to HL conditions did not alter c-Fos responses in serotonergic neurons in any other DR subdivision. In contrast, rats exposed to the open-field arena had increased c-Fos expression in non-serotonergic cells throughout the DR compared to CO rats, and this effect was particularly apparent in the dorsolateral part of the DR. We conclude that exposure to HL conditions, compared to LL conditions, increased anxiety-related behavioral responses in an open-field arena but this stimulus was at or below the threshold required to increase c-Fos expression in serotonergic neurons. PMID:17303505

Report to the Nuclear energy Research Advisory Committee (NERAC) Subcommittee on "Long-Term Isotope Research and Productions Plan" - Responses to Questions

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

Ammoniums

1999-07-01

This report presents responses to two series of questions that were raised by a subcommittee of the Nuclear Energy Research Advisory Committee (NERAC) that has been charged with producing a ''Long-Term Isotope Research and Production Plan.'' The NERAC subcommittee is chaired by Dr. Richard Reba, and the Hanford Site Visit team, which comprises a subset of the subcommittee members, is chaired by Dr. Thomas Ruth. The first set of questions raised by the subcommittee on isotope production at the Hanford Site was received from Dr. Ruth on May 10, 1999, and the second set was received from him on Julymore » 5, 1999. Responses to the first set of questions were prepared as part of a June 1999 report entitled ''Isotope Production at the Hanford Site in Richland, Washington'' (PNNL 1999a). The responses to these questions are summarized in this document, with frequent references to the June 1999 report for additional details. Responses to the second set of questions from the NERAC subcommittee are presented in this document for the first time.« less

Gaia DR1 documentation Chapter 6: Variability

NASA Astrophysics Data System (ADS)

Eyer, L.; Rimoldini, L.; Guy, L.; Holl, B.; Clementini, G.; Cuypers, J.; Mowlavi, N.; Lecoeur-Taïbi, I.; De Ridder, J.; Charnas, J.; Nienartowicz, K.

2017-12-01

This chapter describes the photometric variability processing of the Gaia DR1 data. Coordination Unit 7 is responsible for the variability analysis of over a billion celestial sources. In particular the definition, design, development, validation and provision of a software package for the data processing of photometrically variable objects. Data Processing Centre Geneva (DPCG) responsibilities cover all issues related to the computational part of the CU7 analysis. These span: hardware provisioning, including selection, deployment and optimisation of suitable hardware, choosing and developing software architecture, defining data and scientific workflows as well as operational activities such as configuration management, data import, time series reconstruction, storage and processing handling, visualisation and data export. CU7/DPCG is also responsible for interaction with other DPCs and CUs, software and programming training for the CU7 members, scientific software quality control and management of software and data lifecycle. Details about the specific data treatment steps of the Gaia DR1 data products are found in Eyer et al. (2017) and are not repeated here. The variability content of the Gaia DR1 focusses on a subsample of Cepheids and RR Lyrae stars around the South ecliptic pole, showcasing the performance of the Gaia photometry with respect to variable objects.

Evaluation of Safety and Efficacy of Qinming8631 DR Implantable Cardiac Pacemaker in Chinese Patients: A Prospective, Multicenter, Randomized Controlled Trial of the First Domestically Developed Pacemaker of China.

PubMed

Xiang, Mei-Xiang; Wang, Dong-Qi; Xu, Jing; Zhang, Zheng; Hu, Jian-Xin; Wang, Dong-Mei; Gu, Xiang; Liu, He-Ping; Guo, Tao; Yang, Xiang-Jun; Ling, Feng; Lin, Jia-Feng; Cai, Shang-Lang; Zhu, Guo-Bin; Wang, Jian-An

2016-11-20

High cost of imported pacemakers is a main obstacle for Chinese patients suffering from bradyarrhythmia, and a domestically developed pacemaker will help lower the burden. This study aimed to evaluate the safety and efficacy of Qinming8631 DR (Qinming Medical, Baoji, China), the first domestically developed dual-chamber pacemaker of China, compared with a commercially available pacemaker Talos DR (Biotronik, Berlin, Germany) in Chinese patients. A prospective randomized trial was conducted at 14 centers in China. Participants were randomized into trial (Qinming8631 DR) and control (Talos DR) groups. Parameters of the pacing systems were collected immediately after device implantation and during follow-ups. The effective pacing rate at 6-month follow-up was recorded as the primary end point. Electrical properties, magnet response, single- and double-pole polarity conversion, rate response function, and adverse events of the pacing system were analyzed. The Cochran-Mantel-Haenszel Chi-square test, paired t-test, and Wilcoxon signed-rank test were used for measuring primary qualitative outcomes and comparing normally and abnormally distributed measurement data. A total of 225 patients with a diagnosis of bradyarrhythmia and eligible for this study were randomly enrolled into the trial (n = 113) and control (n = 112) groups. They underwent successful pacemaker implantation with acceptable postoperative pacing threshold and sensitivity. Effective pacing rates of trial and control groups were comparable both in the full analysis set and the per protocol set (81.4% vs. 79.5%, P = 0.712 and 95.4% vs. 89.5%, P = 0.143, respectively). In both data sets, noninferiority of the trial group was above the predefined noninferiority limit(-9.5%). This study established the noninferiority of Qinming8631 DR to Talos DR. The safety and efficacy of Qinming8631 DR pacemaker were comparable to those of Talos DR in treating patients with cardiac bradyarrhythmia.

Contributions of vitamin D response elements and HLA promoters to multiple sclerosis risk.

PubMed

Nolan, David; Castley, Alison; Tschochner, Monika; James, Ian; Qiu, Wei; Sayer, David; Christiansen, Frank T; Witt, Campbell; Mastaglia, Frank; Carroll, William; Kermode, Allan

2012-08-07

The identification of a vitamin D-responsive (VDRE) motif within the HLA-DRB1*15:01 promoter region provides an attractive explanation for the combined effects of HLA-DR inheritance and vitamin D exposure on multiple sclerosis (MS) risk. We therefore sought to incorporate HLA-DRB1 promoter variation, including the VDRE motif, in an assessment of HLA-DRB1-associated MS risk. We utilized 32 homozygous HLA cell lines (covering 17 DRB1 alleles) and 53 heterozygote MS samples (20 DRB1 alleles) for HLA-DRB1 promoter sequencing. The influence of HLA-DRB1 variation on MS risk was then assessed among 466 MS cases and 498 controls. The majority of HLA*DRB1 alleles (including HLA-DRB1*15:01) express the functional VDRE motif, apart from HLA-DRB1*04, *07, and *09 alleles that comprise the HLA-DR53 serologic group. Allele-specific variation within functional X-box and Y-box motifs was also associated with serologically defined HLA-DR haplotypes. Incorporating these results in an analysis of MS risk, we identified a strong protective effect of HLA-DRB1*04, *07, and *09 (DR53) alleles (p = 10(-12)) and elevated risk associated with DRB1*15 and *16 (DR51) and *08 (DR8) alleles (p < 10(-18)). HLA-DRB1 groups corresponding to serologic HLA-DR profiles as well as promoter polymorphism haplotypes effectively stratified MS risk over an 11-fold range, suggesting functional relationships between risk-modifying HLA-DRB1 alleles. An independent contribution of VDRE motif variation to increase MS risk was not discernible, although vitamin D-dependent regulation of HLA-DR expression may still play an important role given that HLA-DRB1*04/*07/*09 (DR53) alleles that express the "nonresponsive" VDRE motif were associated with significantly reduced risk of MS.

Gaia Data Release 1. The archive visualisation service

NASA Astrophysics Data System (ADS)

Moitinho, A.; Krone-Martins, A.; Savietto, H.; Barros, M.; Barata, C.; Falcão, A. J.; Fernandes, T.; Alves, J.; Silva, A. F.; Gomes, M.; Bakker, J.; Brown, A. G. A.; González-Núñez, J.; Gracia-Abril, G.; Gutiérrez-Sánchez, R.; Hernández, J.; Jordan, S.; Luri, X.; Merin, B.; Mignard, F.; Mora, A.; Navarro, V.; O'Mullane, W.; Sagristà Sellés, T.; Salgado, J.; Segovia, J. C.; Utrilla, E.; Arenou, F.; de Bruijne, J. H. J.; Jansen, F.; McCaughrean, M.; O'Flaherty, K. S.; Taylor, M. B.; Vallenari, A.

2017-09-01

Context. The first Gaia data release (DR1) delivered a catalogue of astrometry and photometry for over a billion astronomical sources. Within the panoplyof methods used for data exploration, visualisation is often the starting point and even the guiding reference for scientific thought. However, this is a volume of data that cannot be efficiently explored using traditional tools, techniques, and habits. Aims: We aim to provide a global visual exploration service for the Gaia archive, something that is not possible out of the box for most people. The service has two main goals. The first is to provide a software platform for interactive visual exploration of the archive contents, using common personal computers and mobile devices available to most users. The second aim is to produce intelligible and appealing visual representations of the enormous information content of the archive. Methods: The interactive exploration service follows a client-server design. The server runs close to the data, at the archive, and is responsible for hiding as far as possible the complexity and volume of the Gaia data from the client. This is achieved by serving visual detail on demand. Levels of detail are pre-computed using data aggregation and subsampling techniques. For DR1, the client is a web application that provides an interactive multi-panel visualisation workspace as well as a graphical user interface. Results: The Gaia archive Visualisation Service offers a web-based multi-panel interactive visualisation desktop in a browser tab. It currently provides highly configurable 1D histograms and 2D scatter plots of Gaia DR1 and the Tycho-Gaia Astrometric Solution (TGAS) with linked views. An innovative feature is the creation of ADQL queries from visually defined regions in plots. These visual queries are ready for use in the Gaia Archive Search/data retrieval service. In addition, regions around user-selected objects can be further examined with automatically generated SIMBAD searches. Integration of the Aladin Lite and JS9 applications add support to the visualisation of HiPS and FITS maps. The production of the all-sky source density map that became the iconic image of Gaia DR1 is described in detail. Conclusions: On the day of DR1, over seven thousand users accessed the Gaia Archive visualisation portal. The system, running on a single machine, proved robust and did not fail while enabling thousands of users to visualise and explore the over one billion sources in DR1. There are still several limitations, most noticeably that users may only choose from a list of pre-computed visualisations. Thus, other visualisation applications that can complement the archive service are examined. Finally, development plans for Data Release 2 are presented.

Invariant Natural Killer T Cells Are Pathogenic in the HLA-DR4-Transgenic Humanized Mouse Model of Toxic Shock Syndrome and Can Be Targeted to Reduce Morbidity.

PubMed

Szabo, Peter A; Rudak, Patrick T; Choi, Joshua; Xu, Stacey X; Schaub, Robert; Singh, Bhagirath; McCormick, John K; Haeryfar, S M Mansour

2017-03-01

During toxic shock syndrome (TSS), bacterial superantigens trigger a polyclonal T -cell response leading to a potentially catastrophic "cytokine storm". Whether innate-like invariant natural killer T (iNKT) cells, with remarkable immunomodulatory properties, participate in TSS is unclear. Using genetic and cell depletion approaches, we generated iNKT cell-deficient, superantigen-sensitive HLA-DR4-transgenic (DR4tg) mice, which were compared with their iNKT-sufficient counterparts for responsiveness to staphylococcal enterotoxin B (SEB). Both approaches indicate that iNKT cells are pathogenic in TSS. Importantly, treating DR4tg mice with a TH2-polarizing glycolipid agonist of iNKT cells reduced SEB-inflicted morbidity/mortality. Therefore, iNKT cells may constitute an attractive therapeutic target in superantigen-mediated illnesses. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

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

Takahashi, Takeshi, E-mail: takeshi-takahashi@ciea.or.jp; Katano, Ikumi; Ito, Ryoji

Highlights: • β-Lactoglobulin (BLG) specific TCR genes were introduced to human HSC by retrovirus. • Human HSC with BLG-specific TCR were transplanted into NOG-HLA-DR4 I-A{sup −/−} mice. • BLG-specific TCR induced positive selection of thymocytes. • BLG-specific TCR positive CD4{sup +} T cells mediated immune responses in humanized mice. - Abstract: The development of severe immunodeficient mouse strains containing various human genes, including cytokines or HLA, has enabled the reconstitution of functional human immune systems after transplantation of human hematopoietic stem cells (HSC). Accumulating evidence has suggested that HLA-restricted antigen-specific human T-cell responses can be generated in these humanized mice.more » To directly monitor immune responses of human CD4{sup +} T cells, we introduced β-lactoglobulin (BLG)-specific T cell receptor (TCR) genes derived from CD4{sup +} T-cell clones of cow-milk allergy patients into HSCs, and subsequently transplanted them into NOG-HLA-DR4 transgenic/I-Aβ deficient mice (NOG-DR4/I-A{sup o}). In the thymus, thymocytes with BLG-specific TCR preferentially differentiated into CD4{sup +}CD8{sup −} single-positive cells. Adoptive transfer of mature CD4{sup +} T cells expressing the TCR into recipient NOG-DR4/I-A{sup o} mice demonstrated that human CD4{sup +} T cells proliferated in response to antigenic stimulation and produced IFN-γ in vivo, suggesting that functional T-cell reactions (especially Th1-skewed responses) were induced in humanized mice.« less

Assessing the risk of CMV reactivation and reconstitution of antiviral immune response post bone marrow transplantation by the QuantiFERON-CMV-assay and real time PCR.

PubMed

Krawczyk, Adalbert; Ackermann, Jessica; Goitowski, Birgit; Trenschel, Rudolf; Ditschkowski, Markus; Timm, Jörg; Ottinger, Hellmut; Beelen, Dietrich W; Grüner, Nico; Fiedler, Melanie

CMV reactivation is a major cause of severe complications in allogeneic hematopoietic stem cell transplant (HSCT) recipients. The risk of CMV reactivation depends on the serostatus (+/-) of the donor (D) and recipient (R). The reconstitution of CMV-specific T-cell responses after transplantation is crucial for the control of CMV reactivation. The study aimed to determine the cellular immune status correlating with protection from high-level CMV viremia (>5000 copies/ml) and disease. We monitored CMV-specific cellular immune responses in 9 high-risk (D-/R+), 14 intermediate risk (D+/R+) and 3 low risk individuals (D+/R-), and 8 CMV negative controls (D-/R-). Interferon- γ (IFN-γ) levels as a marker for the CD8+ T-cell response were determined by the QuantiFERON-CMV-assay and compared to viral loads determined by PCR. Early CMV reactivation was detected in all high-risk and 13/14 intermediate risk individuals. High-level viremia was detected in 5/7 high and 7/14 intermediate risk patients. Reconstitution of the CMV-specific cellular immune response started from 3 months after transplantation and resulted in protection against CMV reactivation. Re-establishing of CMV-specific T-cell immune responses with IFN- γ levels >8.9 IU/ml is crucial for protection from high-level CMV viremia. Monitoring of HSCT-recipients with the QuantiFERON-CMV-assay might be of great benefit to optimize antiviral treatment. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

Utilization of DR1 as true RARE in regulating the Ssm, a novel retinoic acid-target gene in the mouse testis.

PubMed

Han, Kyuyong; Song, Haengseok; Moon, Irene; Augustin, Robert; Moley, Kelle; Rogers, Melissa; Lim, Hyunjung

2007-03-01

Various nuclear receptors form dimers to activate target genes via specific response elements located within promoters or enhancers. Retinoid X receptor (RXR) serves as a dimerization partner for many nuclear receptors including retinoic acid receptor (RAR) and peroxisome proliferator-activated receptor (PPAR). Dimers show differential preference towards directly repeated response elements with 1-5 nucleotide spacing, and direct repeat 1 (DR1) is a promiscuous element which recruits RAR/RXR, RXR/RXR, and PPAR/RXR in vitro. In the present investigation, we report identification of a novel RAR/RXR target gene which is regulated by DR1s in the promoter region. This gene, namely spermatocyte-specific marker (Ssm), recruits all the three combinations of nuclear receptors in vitro, but in vivo regulation is observed by trans-retinoic acid-activated RAR/RXR dimer. Indeed, chromatin immunoprecipitation experiment demonstrates binding of RARbeta and RXRalpha in the promoter region of the Ssm. Interestingly, expression of Ssm is almost exclusively observed in spermatocytes in the adult mouse testis, where RA signaling is known to regulate developmental program of male germ cells. The results show that Ssm is a RAR/RXR target gene uniquely using DR1 and exhibits stage-specific expression in the mouse testis with potential function in later stages of spermatogenesis. This finding exemplifies usage of DR1s as retinoic acid response element (RARE) under a specific in vivo context.

Dynamic range of Nef-mediated evasion of HLA class II-restricted immune responses in early HIV-1 infection.

PubMed

Mahiti, Macdonald; Brumme, Zabrina L; Jessen, Heiko; Brockman, Mark A; Ueno, Takamasa

2015-07-31

HLA class II-restricted CD4(+) T lymphocytes play an important role in controlling HIV-1 replication, especially in the acute/early infection stage. But, HIV-1 Nef counteracts this immune response by down-regulating HLA-DR and up-regulating the invariant chain associated with immature HLA-II (Ii). Although functional heterogeneity of various Nef activities, including down-regulation of HLA class I (HLA-I), is well documented, our understanding of Nef-mediated evasion of HLA-II-restricted immune responses during acute/early infection remains limited. Here, we examined the ability of Nef clones from 47 subjects with acute/early progressive infection and 46 subjects with chronic progressive infection to up-regulate Ii and down-regulate HLA-DR and HLA-I from the surface of HIV-infected cells. HLA-I down-regulation function was preserved among acute/early Nef clones, whereas both HLA-DR down-regulation and Ii up-regulation functions displayed relatively broad dynamic ranges. Nef's ability to down-regulate HLA-DR and up-regulate Ii correlated positively at this stage, suggesting they are functionally linked in vivo. Acute/early Nef clones also exhibited higher HLA-DR down-regulation and lower Ii up-regulation functions compared to chronic Nef clones. Taken together, our results support enhanced Nef-mediated HLA class II immune evasion activities in acute/early compared to chronic infection, highlighting the potential importance of these functions following transmission. Copyright © 2015 Elsevier Inc. All rights reserved.

Preserving Genome Integrity: The DdrA Protein of Deinococcus radiodurans R1

PubMed Central

Harris, Dennis R; Tanaka, Masashi; Saveliev, Sergei V; Jolivet, Edmond; Earl, Ashlee M; Cox, Michael M

2004-01-01

The bacterium Deinococcus radiodurans can withstand extraordinary levels of ionizing radiation, reflecting an equally extraordinary capacity for DNA repair. The hypothetical gene product DR0423 has been implicated in the recovery of this organism from DNA damage, indicating that this protein is a novel component of the D. radiodurans DNA repair system. DR0423 is a homologue of the eukaryotic Rad52 protein. Following exposure to ionizing radiation, DR0423 expression is induced relative to an untreated control, and strains carrying a deletion of the DR0423 gene exhibit increased sensitivity to ionizing radiation. When recovering from ionizing-radiation-induced DNA damage in the absence of nutrients, wild-type D. radiodurans reassembles its genome while the mutant lacking DR0423 function does not. In vitro, the purified DR0423 protein binds to single-stranded DNA with an apparent affinity for 3′ ends, and protects those ends from nuclease degradation. We propose that DR0423 is part of a DNA end-protection system that helps to preserve genome integrity following exposure to ionizing radiation. We designate the DR0423 protein as DNA damage response A protein. PMID:15361932

KSC-94PC-0901

NASA Image and Video Library

1994-07-20

KENNEDY SPACE CENTER, FLA. -- Dr. Irene Duhart Long is the director, Biomedical Operations and Research Office, at the Kennedy Space Center effective July 24, 1994. She is responsible for the program management of the center's aerospace and occupational medicine, life sciences research, environmental health programs and the operations management of the life sciences support facilities. Dr. Long also is responsible for providing the coordinating medical, environmental monitoring and environmental health support to launch and landing activities and day-to-day institutional functions.

Fibroblast Growth Factor 8 Deficiency Compromises the Functional Response of the Serotonergic System to Stress

PubMed Central

Brooks, Leah R.; Pals, Heide L.; Enix, Courtney L.; Woolaver, Rachel A.; Paul, Evan D.; Lowry, Christopher A.; Tsai, Pei-San

2014-01-01

Functionally heterogeneous populations of serotonergic neurons, located within the dorsal raphe nucleus (DR), play a role in stress-related behaviors and neuropsychiatric illnesses such as anxiety and depression. Abnormal development of these neurons may permanently alter their structure and connections, making the organism more susceptible to anxiety-related disorders. A factor that critically regulates the development of serotonergic neurons is fibroblast growth factor 8 (Fgf8). In this study, we used acute restraint stress followed by behavioral testing to examine whether Fgf8 signaling during development is important for establishing functional stress- and anxiety-related DR neurocircuits in adulthood. Wild-type and heterozygous male mice globally hypomorphic for Fgf8 were exposed to acute restraint stress and then tested for anxiety-like behavior on the elevated plus-maze. Further, we measured c-Fos immunostaining as a marker of serotonergic neuronal activation and tissue 5-hydroxyindoleacetic acid concentrations as a marker of serotonin functional output. Results showed that Fgf8 hypomorphs exhibited 1) an exaggerated response of DR anxiety-promoting circuits and 2) a blunted response of a DR panic-inhibiting circuit to stress, effects that together were associated with increased baseline anxiety-like behavior. Overall, our results provide a neural substrate upon which Fgf8 deficiency could affect stress response and support the hypothesis that developmental disruptions of serotonergic neurons affect their postnatal functional integrity. PMID:24992493

Fibroblast growth factor 8 deficiency compromises the functional response of the serotonergic system to stress.

PubMed

Brooks, Leah R; Pals, Heide L; Enix, Courtney L; Woolaver, Rachel A; Paul, Evan D; Lowry, Christopher A; Tsai, Pei-San

2014-01-01

Functionally heterogeneous populations of serotonergic neurons, located within the dorsal raphe nucleus (DR), play a role in stress-related behaviors and neuropsychiatric illnesses such as anxiety and depression. Abnormal development of these neurons may permanently alter their structure and connections, making the organism more susceptible to anxiety-related disorders. A factor that critically regulates the development of serotonergic neurons is fibroblast growth factor 8 (Fgf8). In this study, we used acute restraint stress followed by behavioral testing to examine whether Fgf8 signaling during development is important for establishing functional stress- and anxiety-related DR neurocircuits in adulthood. Wild-type and heterozygous male mice globally hypomorphic for Fgf8 were exposed to acute restraint stress and then tested for anxiety-like behavior on the elevated plus-maze. Further, we measured c-Fos immunostaining as a marker of serotonergic neuronal activation and tissue 5-hydroxyindoleacetic acid concentrations as a marker of serotonin functional output. Results showed that Fgf8 hypomorphs exhibited 1) an exaggerated response of DR anxiety-promoting circuits and 2) a blunted response of a DR panic-inhibiting circuit to stress, effects that together were associated with increased baseline anxiety-like behavior. Overall, our results provide a neural substrate upon which Fgf8 deficiency could affect stress response and support the hypothesis that developmental disruptions of serotonergic neurons affect their postnatal functional integrity.

Responsiveness of a Neuromuscular Recovery Scale for Spinal Cord Injury: Inpatient and Outpatient Rehabilitation

DTIC Science & Technology

2013-10-01

Velozo’s research focus is on the development of functional outcome measures using Rasch measurement theory. Dr. Velozo’s research team has...functional outcome measures using Rasch measurement theory. Dr. Velozo’s research team has developed computerized adaptive measurement of physical

The Relationship Between Visual Sensor Equipment in Flying Insects and their Flight Performance -- a Neurobio-Engineering Approach

DTIC Science & Technology

2014-03-16

College in the Department of Bioengineering with: Dr Martyn Boutelle (Biosensors), Dr Simon Schultz (Neural Coding), Dr Manos Drakakis (Low-power VLSI...in the fly gaze stabilization system. PLoS Biology, 6(7):e173 (2008). O27. Saleem A, Krapp H.G., and Schultz S.R.: Spike-triggered independent...D., Krapp H.G., Schultz S.R.: Bimodal optomotor response to plaids in blowflies: mechanisms of component selectivity and evidence for pattern

The correlation between preoperative volumetry and real graft weight: comparison of two volumetry programs

PubMed Central

Mussin, Nadiar; Sumo, Marco; Choi, YoungRok; Choi, Jin Yong; Ahn, Sung-Woo; Yoon, Kyung Chul; Kim, Hyo-Sin; Hong, Suk Kyun; Yi, Nam-Joon; Suh, Kyung-Suk

2017-01-01

Purpose Liver volumetry is a vital component in living donor liver transplantation to determine an adequate graft volume that meets the metabolic demands of the recipient and at the same time ensures donor safety. Most institutions use preoperative contrast-enhanced CT image-based software programs to estimate graft volume. The objective of this study was to evaluate the accuracy of 2 liver volumetry programs (Rapidia vs. Dr. Liver) in preoperative right liver graft estimation compared with real graft weight. Methods Data from 215 consecutive right lobe living donors between October 2013 and August 2015 were retrospectively reviewed. One hundred seven patients were enrolled in Rapidia group and 108 patients were included in the Dr. Liver group. Estimated graft volumes generated by both software programs were compared with real graft weight measured during surgery, and further classified into minimal difference (≤15%) and big difference (>15%). Correlation coefficients and degree of difference were determined. Linear regressions were calculated and results depicted as scatterplots. Results Minimal difference was observed in 69.4% of cases from Dr. Liver group and big difference was seen in 44.9% of cases from Rapidia group (P = 0.035). Linear regression analysis showed positive correlation in both groups (P < 0.01). However, the correlation coefficient was better for the Dr. Liver group (R2 = 0.719), than for the Rapidia group (R2 = 0.688). Conclusion Dr. Liver can accurately predict right liver graft size better and faster than Rapidia, and can facilitate preoperative planning in living donor liver transplantation. PMID:28382294

What is the effect of fasting on the lifespan of neurons?

PubMed

Kalsi, Dilraj S

2015-11-01

Medical advancements have increased life expectancy but have consequently increased the incidence of age-related disease. Fasting or dietary restriction (DR) can help prevent these via anti-ageing effects; however, these effects in neurons are less well characterized. Here, a series of animal and human studies of the effects of DR on the structural and functional integrity of neurons and the underlying mechanisms are analyzed. DR improves the integrity of animal neurons via a wide range of possible mechanisms including changes in metabolism, oxidative damage, stress responses, growth factors, and gene expression. These mechanisms are extensively interlinked and point to an optimum range of calorie intake, above calorie deprivation and below burdensome calorie excess. Human studies also suggest that DR improves neuron integrity; however, due to ethical and methodological limitations, the most conclusive data on DR hinge upon on-going life-long monkey experiments. Rather than developing pharmacological mimetics of DR, our focus should be on educating the public about DR in order to minimize age-related disease. Copyright © 2015 Elsevier B.V. All rights reserved.

A benders decomposition approach to multiarea stochastic distributed utility planning

NASA Astrophysics Data System (ADS)

McCusker, Susan Ann

Until recently, small, modular generation and storage options---distributed resources (DRs)---have been installed principally in areas too remote for economic power grid connection and sensitive applications requiring backup capacity. Recent regulatory changes and DR advances, however, have lead utilities to reconsider the role of DRs. To a utility facing distribution capacity bottlenecks or uncertain load growth, DRs can be particularly valuable since they can be dispersed throughout the system and constructed relatively quickly. DR value is determined by comparing its costs to avoided central generation expenses (i.e., marginal costs) and distribution investments. This requires a comprehensive central and local planning and production model, since central system marginal costs result from system interactions over space and time. This dissertation develops and applies an iterative generalized Benders decomposition approach to coordinate models for optimal DR evaluation. Three coordinated models exchange investment, net power demand, and avoided cost information to minimize overall expansion costs. Local investment and production decisions are made by a local mixed integer linear program. Central system investment decisions are made by a LP, and production costs are estimated by a stochastic multi-area production costing model with Kirchhoff's Voltage and Current Law constraints. The nested decomposition is a new and unique method for distributed utility planning that partitions the variables twice to separate local and central investment and production variables, and provides upper and lower bounds on expected expansion costs. Kirchhoff's Voltage Law imposes nonlinear, nonconvex constraints that preclude use of LP if transmission capacity is available in a looped transmission system. This dissertation develops KVL constraint approximations that permit the nested decomposition to consider new transmission resources, while maintaining linearity in the three individual models. These constraints are presented as a heuristic for the given examples; future research will investigate conditions for convergence. A ten-year multi-area example demonstrates the decomposition approach and suggests the ability of DRs and new transmission to modify capacity additions and production costs by changing demand and power flows. Results demonstrate that DR and new transmission options may lead to greater capacity additions, but resulting production cost savings more than offset extra capacity costs.

A recombinant subunit vaccine for bovine RSV and Histophilus somni protects calves against dual pathogen challenge.

PubMed

Gershwin, Laurel J; Behrens, Nicole E; McEligot, Heather A; Carvallo-Chaigneau, Francisco R; Crum, Lauren T; Gunnarson, Brianna M; Corbeil, Lynette B

2017-04-04

Bovine respiratory syncytial virus (BRSV) and Histophilus somni synergize to cause respiratory disease in cattle. These pathogens cause enhanced disease during dual-infection and an IgE response to antigens of H. somni in dual-infected but not singly infected calves. Vaccines containing whole inactivated BRSV or H. somni have been associated with IgE responses A vaccine strategy that avoids stimulation of IgE antibodies would provide superior protection from dual infection. We hypothesized that a subunit vaccine consisting of the nucleoprotein (NP) from BRSV and the recombinant antigen IbpA DR2 (a surface antigen of H. somni with two toxic fic motifs) in Quil A adjuvant would elicit protection without disease enhancement. Three groups of calves were vaccinated twice with either: Formalin inactivated BRSV (FI) plus Somnivac®, NP & IbpA DR2 plus Quil A or Quil A alone, followed by BRSV and H. somni challenge. Clinical scores and antibody levels (to whole pathogens and to the subunits) were evaluated. Lungs were examined at necropsy on day 23 after infection. Clinical scores were significantly greatest for the FI & Somnivac® group and both clinical scores and lung pathology were lowest for the subunit group. All calves shed BRSV in nasal secretions. FI & Somnivac® induced IgE antibodies to H. somni and BRSV, but not to NP or DR2. The subunit vaccine did not induce an IgE antibody response to IbpA DR2 antigen and induced little IgE to H. somni. It did not induce an IgG antibody response to BRSV and H. somni, but stimulated production of IgG antibodies against the subunits. In summary, the subunit vaccine, consisting of the BRSV NP and H. somni IbpA DR2 in Quil A, protected against severe clinical signs and decreased lung pathology but did not prevent viral shedding. Importantly it prevented synergistic disease expression in response to dual infection. Copyright © 2017 Elsevier Ltd. All rights reserved.

Ethical Realism: A Guide to Action?

ERIC Educational Resources Information Center

Matkin, Gary

2008-01-01

This article presents the author's response to Gary Miller's essay entitled "Ethical Realism and Continuing Education." In his essay, Dr. Miller has provided a valuable opportunity to reflect on the practice of continuing education (CE) leadership. Dr. Miller reviews six principles that are encapsulated in the concept of ethical realism, but are…

Debate on the Chernobyl disaster: response to Dr. Sergei V. Jargin.

PubMed

Yablokov, Alexey

2012-01-01

The author responds, point by point, to Dr. Jargin's critique in this Journal issue of A. V. Yablokov, V. B. Nesterenko, and A. B. Nesterenko, Chernobyl: consequences of the catastrophe for people and the environment, published in 2009 by the New York Academy of Sciences.

Appropriateness Measurement with Polychotomous Item Response Models and Standardized Indices.

DTIC Science & Technology

1984-04-01

Knoxville, TN � Lawrence, KS 66045 I Dr. John B. Carroll I ERIC Facility-Acquisitions -. ’ 409 Elliott Rd. 4833 Rugby Avenue Chapel Hill, NC...90007 University of Missouri Columbia, MO 65201 1 German Military Representative ATTN: Wolfgang Wildegrube 1 Dr. V. R. R. Uppuluri Streitkraefteast Union

Global Proliferation-Dynamics, Acquisition Strategies, and Responses. Volume 2. Nuclear Proliferation

DTIC Science & Technology

1994-09-01

due to Marvin Atkins, Joel Bengston. Richard Blumstein. John Bulger, James Bushong, Burrus Carnahan, Alexis Castor, Emerory Chase, Edward Chaves...SCIENCE BOARDATTN: DR P G K MINSKI OSD (DDR&E) ATTN: DR VICTOR REIS DEPUTY ASSISTANT SECRETARY OSD COMPTROLLER ATTN: JANE MATTHIAS ATTN: HONORABLE JOHN

Different Weather

ERIC Educational Resources Information Center

Stephens, Jonathan

2007-01-01

This article is a response to Rhoda Bernard's (2005) article, "Making Music, Making Selves". The author first met Dr. Bernard several years ago in the UK, at an international music education research conference at the University of Exeter. Without realising he was in the audience, Dr. Bernard cited his 1995 article "Artist or Teacher?" as an early…

Hyperglycaemia in pregnant rats causes sex-related vascular dysfunction in adult offspring: role of cyclooxygenase-2.

PubMed

de Sá, Francine Gomes; de Queiroz, Diego Barbosa; Ramos-Alves, Fernanda Elizabethe; Santos-Rocha, Juliana; da Silva, Odair Alves; Moreira, Hicla Stefany; Leal, Geórgia Andrade; da Rocha, Marcelo Aurélio; Duarte, Gloria Pinto; Xavier, Fabiano Elias

2017-08-01

What is the central question of this study? Hyperglycaemia during pregnancy induces vascular dysfunction and hypertension in male offspring. Given that female offspring from other fetal programming models are protected from the effects of fetal insult, the present study investigated whether there are sex differences in blood pressure and vascular function in hyperglycaemia-programmed offspring. What is the main finding and its importance? We demonstrated that hyperglycaemia in pregnant rats induced vascular dysfunction and hypertension only in male offspring. We found sex differences in oxidative stress and cyclooxygenase-2-derived prostanoid production that might underlie the vascular dysfunction. These differences, particularly in resistance arteries, may in part explain the absence of hypertension in female offspring born to hyperglycaemic dams. Exposure to maternal hyperglycaemia induces hypertension and vascular dysfunction in adult male offspring. Given that female offspring from several fetal programming models are protected from the effects of fetal insult, in this study we analysed possible differences relative to sex in blood pressure and vascular function in hyperglycaemia-programmed offspring. Hyperglycaemia was induced on day 7 of gestation (streptozotocin, 50 mg kg -1 ). Blood pressure, acetylcholine and phenylephrine or noradrenaline responses were analysed in the aorta and mesenteric resistance arteries of 3-, 6- and 12-month-old male and female offspring. Thromboxane A 2 release was analysed with commercial kits and superoxide anion (O 2 - ) production by dihydroethidium-emitted fluorescence. Male but not female offspring of hyperglycaemic dams (O-DR) had higher blood pressure than control animals (O-CR). Contraction in response to phenylephrine increased and relaxation in response to acetylcholine decreased only in the aorta from 12-month-old male O-DR and not in age-matched O-CR. Contractile and vasodilator responses were preserved in both the aorta and mesenteric resistance arteries from female O-DR of all ages. Pre-incubation with tempol, superoxide dismutase, indomethacin, NS-398, furegrelate or SQ29548 decreased contraction in response to phenylephrine and potentiated relaxation in response to acetylcholine in 12-month-old male O-DR aorta. In this artery, thromboxane A 2 release and O 2 - generation were greater in O-DR than O-CR groups. In conclusion, exposure to hyperglycaemia in utero results in sex-specific and age-dependent hypertension. The fact that vascular function is preserved in female O-DR may in part explain the absence of hypertension in this group. In contrast, the peripheral artery dysfunction associated with increased cyclooxygenase-2-derived production of vasoconstrictor prostanoids could underlie the increased blood pressure in male O-DR. © 2017 The Authors. Experimental Physiology © 2017 The Physiological Society.

CancerDR: cancer drug resistance database.

PubMed

Kumar, Rahul; Chaudhary, Kumardeep; Gupta, Sudheer; Singh, Harinder; Kumar, Shailesh; Gautam, Ankur; Kapoor, Pallavi; Raghava, Gajendra P S

2013-01-01

Cancer therapies are limited by the development of drug resistance, and mutations in drug targets is one of the main reasons for developing acquired resistance. The adequate knowledge of these mutations in drug targets would help to design effective personalized therapies. Keeping this in mind, we have developed a database "CancerDR", which provides information of 148 anti-cancer drugs, and their pharmacological profiling across 952 cancer cell lines. CancerDR provides comprehensive information about each drug target that includes; (i) sequence of natural variants, (ii) mutations, (iii) tertiary structure, and (iv) alignment profile of mutants/variants. A number of web-based tools have been integrated in CancerDR. This database will be very useful for identification of genetic alterations in genes encoding drug targets, and in turn the residues responsible for drug resistance. CancerDR allows user to identify promiscuous drug molecules that can kill wide range of cancer cells. CancerDR is freely accessible at http://crdd.osdd.net/raghava/cancerdr/

Whose Death Is It Anyway? Perspectives on End-of-Life in Canada.

PubMed

Taylor, Maureen; Martin, Sandra

2014-01-01

People die every minute in Canada, but how they die has become increasingly contentious as the demand for physician-assisted death and euthanasia has become louder and more widespread. Several events have propelled the debate around choice in end-of-life care, including the posthumous release of a video in which infectious disease expert Dr. Donald Low expressed his frustrations over his inability to control the manner of his death, the passing of Bill 52 in Quebec and the Supreme Court's decision to hear the Carter case challenging the constitutionality of the law against assisted suicide. Baby boomers are demanding more autonomy and choice in dying. Is the medical profession listening?

The circumstances of the missing biographer or why Watson didn't narrate these four Sherlock Holmes stories.

PubMed

Caplan, R M

1982-06-01

The author provides arguments to explain why four of Arthur Conan Doyle's sixty stories about Sherlock Holmes were not narrated by Dr. Watson. The arguments relate to logical demands of the plot in the cases of the two stories told by an unidentified narrator. The two told by Holmes seem to demand Watson's absence because the final elucidation requires skill in cutaneous diagnosis; the presence of a medical man would have, or should have, relieved the dramatic tension of the mystery too soon. The Sherlock Holmes stories can provide delightful diversion as well as serve constantly to enhance our appreciation for highly alert and careful physical examination.

ARC-2010-ACD10-0243-002

NASA Image and Video Library

2010-12-22

Wireless crop water monitoring project: Dr. Chris Lund and Forrest Melton, California State University Monterey Bay research scientists who work at NASA Ames Research Center, check data being returned from a wireless soil moisture monitoring network, installed in an agricultural field. Data from the soil moisture sensor network will be used to assist in interpretation of the satellite estimates of crop water demand. Image of courtesy of Forrest S. Melton

miR-133b Regulation of Connective Tissue Growth Factor

PubMed Central

Gjymishka, Altin; Pi, Liya; Oh, Seh-Hoon; Jorgensen, Marda; Liu, Chen; Protopapadakis, Yianni; Patel, Ashnee; Petersen, Bryon E.

2017-01-01

miRNAs are involved in liver regeneration, and their expression is dysregulated in hepatocellular carcinoma (HCC). Connective tissue growth factor (CTGF), a direct target of miR-133b, is crucial in the ductular reaction (DR)/oval cell (OC) response for generating new hepatocyte lineages during liver injury in the context of hepatotoxin-inhibited hepatocyte proliferation. Herein, we investigate whether miR-133b regulation of CTGF influences HCC cell proliferation and migration, and DR/OC response. We analyzed miR-133b expression and found it to be down-regulated in HCC patient samples and induced in the rat DR/OC activation model of 2-acetylaminofluorene with partial hepatectomy. Furthermore, overexpression of miR-133b via adenoviral system in vitro led to decreased CTGF expression and reduced proliferation and Transwell migration of both HepG2 HCC cells and WBF-344 rat OCs. In vivo, overexpression of miR-133b in DR/OC activation models of 2-acetylaminofluorene with partial hepatectomy in rats, and 3,5-diethoxycarbonyl-1,4-dihydrocollidine in mice, led to down-regulation of CTGF expression and OC proliferation. Collectively, these results show that miR-133b regulation of CTGF is a novel mechanism critical for the proliferation and migration of HCC cells and OC response. PMID:26945106

Design and Implementation of Demand Response Information Interactive Service Platform Based on “Internet Plus” Smart Energy

NASA Astrophysics Data System (ADS)

Cui, Gaoying; Fan, Jie; Qin, Yuchen; Wang, Dong; Chen, Guangyan

2017-05-01

In order to promote the effective use of demand response load side resources, promote the interaction between supply and demand, enhance the level of customer service and achieve the overall utilization of energy, this paper briefly explain the background significance of design demand response information platform and current situation of domestic and foreign development; Analyse the new demand of electricity demand response combined with the application of Internet and big data technology; Design demand response information platform architecture, construct demand responsive system, analyse process of demand response strategy formulate and intelligent execution implement; study application which combined with the big data, Internet and demand response technology; Finally, from information interaction architecture, control architecture and function design perspective design implementation of demand response information platform, illustrate the feasibility of the proposed platform design scheme implemented in a certain extent.

Toward a US Army Pacific (USARPAC) rapid deployment medical component in support of Human Assistance/Disaster Relief (HA/DR) operations: challenges with "Going in Light".

PubMed

Johnson, Ralph J

2016-01-01

This article reports the exploratory development and study efforts regarding the viability of a novel "going-in light" or "Going Light" medical component in support of US Army Pacific (USARPAC) Humanitarian Assistance/Disaster Relief (HA/DR) missions, namely, a BLU-MED ® incremental modular equipment package along with a Rapid Deployment Medical Team (RDMT). The study was conducted to uncover a way for the U.S. Army to: (1) better medically support the greater U.S. military Pacific Command, (2) prepare the Army for Pacific HA/DR contingencies, and (3) imprint a swift presence and positive contribution to Pacific HA/DR operations. The findings were derived from an intensive quasi-Military Decision Making Planning (MDMP) process, specifically, the Oracle Delphi. This process was used to: (1) review a needs assessment on the profile of disasters in general and the Pacific in particular and (2) critically examine the viability and issues surrounding a Pacific HA/DR medical response of going in light and incrementally. The Pacific area of operations contains 9 of 15 countries most at risk for disasters in the most disaster-prone region of the world. So, it is not a matter of whether a major, potentially large-scale lethal disaster will occur but rather when. Solid empirical research has shown that by every outcome measured Joint Forces (Army, Navy, Air Force, and Marines) medical HA/DR operations have been inordinately successful and cost-effective when they employed U.S. Army medical assets inland near disasters' kinetic impact and combined sister services' logistical support and expertise. In this regard, USARPAC has the potential to go in light and successfully fill a vital HA/DR medical response gap with the RDMT and a BLU-MED ® . However, initially going in fast and light and expanding and contracting as the situation dictates comes with subsequent challenges as briefly described herein that must be addressed. The challenges to going in light are not insurmountable "show stoppers." They can be identified and addressed through planning and preparation. Hopefully, the acquisition rapid response light components will equip commanders with more effective options with which to conduct Pacific HA/DR operations and be a focal point for effective joint operations.

A dangerous movie? Hollywood does psychoanalysis.

PubMed

Ferrell, Donald R; Silverman, Martin A

2014-12-01

After the appearance of David Cronenberg's film A Dangerous Method in 2011, dealing with the relationships of Sigmund Freud, C. G. Jung and Sabina Spielrein, Dr. Donald Ferrell published: A Dangerous Method, A Film Directed by David Cronenberg: An Extended Review (Ferrell 2012) in the Journal of Religion and Health. Upon its publication, Dr. Ferrell's article was nominated for a Gradiva Award by the National Association for the Advancement of Psychoanalysis. On November 1, 2013, the Association for the Psychoanalysis of Culture and Society held its annual conference at Rutgers University, New Brunswick, NJ. Dr. Billie Pivnick, a member at large of the Board of Directors of the APCS and also on the Editorial Board of the Journal of Religion and Health, persuaded the 2013 Conference Program Committee that Cronenberg's film would make an interesting subject for discussion for conference participants. To that end, Dr. Pivnick invited Dr. Ferrell, C. G. Jung Institute of New York, Dr. Steven Reisner, Coalition for an Ethical Psychology, and Dr. Martin Silverman, Training and Supervising Analyst and Supervising Child Analyst at the Institute for Psychoanalytic Education, NYU College of Medicine, Training and Supervising Analyst at the Center for Psychotherapy and Psychoanalysis of New Jersey, and Associate Editor of The Psychoanalytic Quarterly to serve as panel members to discuss: A Dangerous Movie? Hollywood does Psychoanalysis. Presentations on Cronenberg's film and the early history of psychoanalysis were given by Drs. Ferrell and Reisner, followed by a response to their presentations by Dr. Silverman. Dr. Pivnick chaired the session. The articles presented here were given originally at the APCS conference by Dr. Ferrell and Dr. Silverman. Dr. Reisner declined the invitation to submit his presentation for publication. Dr. Silverman's remarks were based not only on the presentation given by Dr. Ferrell at the session on A Dangerous Movie?, but also on his close and careful reading of the extended review of Cronenberg's film Dr. Ferrell published in the Journal of Religion and Health, as well as Dr. Reisner's presentation. It was appropriate for Dr. Silverman to serve in his capacity as discussant since he had earlier published a critical review of A Secret Symmetry. Sabina Spielrein Between Jung and Freud by Aldo Carotenuto (Silverman 1985).

The lifespan-reproduction trade-off under dietary restriction is sex-specific and context-dependent.

PubMed

Adler, Margo I; Cassidy, Elizabeth J; Fricke, Claudia; Bonduriansky, Russell

2013-06-01

Adult dietary restriction (DR) extends lifespan, but the mechanisms that underlie this effect are not well understood. Many DR studies have demonstrated that lifespan extension tends to be accompanied by a reduction in female fecundity - a correlation widely interpreted as evidence that DR triggers an adaptive re - allocation of resources from reproduction to somatic maintenance. Yet, recent evidence suggests that survival and fecundity need not always trade off under DR, calling the re-allocation hypothesis into question. Because the effects of DR on both survival and reproduction have rarely been tested in both sexes, or under a range of ecologically-relevant environments, the generality of this trade-off remains unclear. We examined the effects of DR on survival and reproduction in both sexes and across a range of environments (larval diet quality and adult sex ratio) in the neriid fly Telostylinus angusticollis. We found that the lifespan-reproduction trade-off is both context- and sex-dependent. Although DR extended lifespan in both sexes by 65% and rendered females completely infertile, costs of DR on male fecundity were subtle and evident only in particular environmental combinations. Our findings suggest that a re-allocation of resources may not underlie the lifespan extension response to DR. Instead, full feeding may be associated with increased costs in comparison to DR, such that lifespan extension may be achieved without an increased resource investment to the soma. Copyright © 2013 Elsevier Inc. All rights reserved.

Human cytomegalovirus alters localization of MHC class II and dendrite morphology in mature Langerhans cells.

PubMed

Lee, Andrew W; Hertel, Laura; Louie, Ryan K; Burster, Timo; Lacaille, Vashti; Pashine, Achal; Abate, Davide A; Mocarski, Edward S; Mellins, Elizabeth D

2006-09-15

Hemopoietic stem cell-derived mature Langerhans-type dendritic cells (LC) are susceptible to productive infection by human CMV (HCMV). To investigate the impact of infection on this cell type, we examined HLA-DR biosynthesis and trafficking in mature LC cultures exposed to HCMV. We found decreased surface HLA-DR levels in viral Ag-positive as well as in Ag-negative mature LC. Inhibition of HLA-DR was independent of expression of unique short US2-US11 region gene products by HCMV. Indeed, exposure to UV-inactivated virus, but not to conditioned medium from infected cells, was sufficient to reduce HLA-DR on mature LC, implicating particle binding/penetration in this effect. Reduced surface levels reflected an altered distribution of HLA-DR because total cellular HLA-DR was not diminished. Accumulation of HLA-DR was not explained by altered cathepsin S activity. Mature, peptide-loaded HLA-DR molecules were retained within cells, as assessed by the proportion of SDS-stable HLA-DR dimers. A block in egress was implicated, as endocytosis of surface HLA-DR was not increased. Immunofluorescence microscopy corroborated the intracellular retention of HLA-DR and revealed markedly fewer HLA-DR-positive dendritic projections in infected mature LC. Unexpectedly, light microscopic analyses showed a dramatic loss of the dendrites themselves and immunofluorescence revealed that cytoskeletal elements crucial for the formation and maintenance of dendrites are disrupted in viral Ag-positive cells. Consistent with these dendrite effects, HCMV-infected mature LC exhibit markedly reduced chemotaxis in response to lymphoid chemokines. Thus, HCMV impedes MHC class II molecule trafficking, dendritic projections, and migration of mature LC. These changes likely contribute to the reduced activation of CD4+ T cells by HCMV-infected mature LC.

7(th) International Immunoglobulin Conference: Poster presentations.

PubMed

Warnatz, K; Ballow, M; Stangel, M; Bril, V

2014-12-01

Immunoglobulin (Ig) therapy is the mainstay of treatment for primary antibody deficiency disorders and has proved to be efficacious in specific autoimmune and inflammatory diseases. Additionally, due to the role of Ig in complement activation, it is being used increasingly in solid organ transplantation. Furthermore, Ig is the primary or secondary treatment in some immune-mediated neuropathies such as chronic inflammatory demyelinating polyneuropathy (CIDP) or multifocal motor neuropathy (MMN). This session discusses trends of Ig use in Europe, proposed mechanisms of action, adverse effects and the potential role of Ig therapy in transplantation. Dr Šedivá reported that Ig therapy is available in all European countries, although dosing is not always optimal, due partly to reimbursement plans. Subcutaneous immunoglobulin (SCIg) has become increasingly accessible in recent years; however, the chosen route of administration still varies widely between countries. Dr Berger's presentation on optimization of Ig therapy in neuropathies, and Dr Rojavin's report on a pharmacometric model to determine the serum IgG levels achieved by different dosing regimens in primary antibody deficiency (PAD) patients, led to the challenging concept of using individualized dosing strategies. Dr Klehmet reported on the potential benefit of using antigen-specific T cell responses as a biomarker of IVIg responsiveness in CIDP patients, while Dr von Gunten provided an insight into the mechanisms of action of Ig preparations, suggesting that the immunoregulatory effects of IgG may be mediated by IgG antibodies against glycans. Dr Basta reported on the potential thrombogenic adverse effects associated with Ig therapy. Although these adverse events are rare, further studies are needed to clarify the relationship between Ig replacement and immunomodulatory therapy and these adverse reactions. In transplantation, Dr Carbone described that prophylactic IVIg treatment was found to decrease the incidence of severe infection in IgG hypogammaglobulinaemia patients undergoing heart transplantations. Furthermore, Dr Clatworthy reported that inactivating polymorphisms in the inhibitory receptor FcγRIIB do not impact upon kidney allograft survival. © 2014 British Society for Immunology.

Wernher von Braun

NASA Image and Video Library

1968-01-22

Dr. Wernher Von Braun, stands in front of a Saturn IB Launch Vehicle at Kennedy Space Center (KSC). Dr. Von Braun was Marshall's first Center Director (1960-1970). Under his leadership Marshall was responsible for the development of the Saturn rockets, the Skylab project and getting the United States into Space and landing on the moon with the Apollo missions.

Reflections on a life in biomedicine: leading change.

PubMed

Nabel, Elizabeth G

2013-09-01

Dr. Elizabeth Nabel delivered the following presentation as the Lee E. Farr Lecturer on May 7, 2013, which served as the culmination of the annual Student Research Day at Yale School of Medicine. Dr. Nabel is President of the Brigham and Women's Hospital in Boston, Massachusetts, and Professor of Medicine at Harvard Medical School. Her lecture to Yale medical students portrayed her own personal and professional journey through medicine as a series of opportunities. Dr. Nabel focused on the roles and responsibilities of physicians to recognize need and to make change through focused advocacy.

The role of glutamic or aspartic acid in position four of the epitope binding motif and thyrotropin receptor-extracellular domain epitope selection in Graves' disease.

PubMed

Inaba, Hidefumi; Martin, William; Ardito, Matt; De Groot, Anne Searls; De Groot, Leslie J

2010-06-01

Development of Graves' disease (GD) is related to HLA-DRB1*0301 (DR3),and more specifically to arginine at position 74 of the DRB1 molecule. The extracellular domain (ECD) of human TSH receptor (hTSH-R) contains the target antigen. We analyzed the relation between hTSH-R-ECD peptides and DR molecules to determine whether aspartic acid (D) or glutamic acid (E) at position four in the binding motif influenced selection of functional epitopes. Peptide epitopes from TSH-R-ECD with D or E in position four (D/E+) had higher affinity for binding to DR3 than peptides without D/E (D/E-) (IC(50) 29.3 vs. 61.4, P = 0.0024). HLA-DR7, negatively correlated with GD, and DRB1*0302 (HLA-DR18), not associated with GD, had different profiles of epitope binding. Toxic GD patients who are DR3+ had higher responses to D/E+ peptides than D/E- peptides (stimulation index 1.42 vs. 1.22, P = 0.028). All DR3+ GD patients (toxic + euthyroid) had higher responses, with borderline significance (Sl; 1.32 vs. 1.18, P = 0.051). Splenocytes of DR3 transgenic mice immunized to TSH-R-ECD responded to D/E+ peptides more than D/E- peptides (stimulation index 1.95 vs. 1.69, P = 0.036). Seven of nine hTSH-R-ECD peptide epitopes reported to be reactive with GD patients' peripheral blood mononuclear cells contain binding motifs with D/E at position four. TSH-R-ECD epitopes with D/E in position four of the binding motif bind more strongly to DRB1*0301 than epitopes that are D/E- and are more stimulatory to GD patients' peripheral blood mononuclear cells and to splenocytes from mice immunized to hTSH-R. These epitopes appear important in immunogenicity to TSH-R due to their favored binding to HLA-DR3, thus increasing presentation to T cells.

Dietary restriction decreases coenzyme Q and ubiquinol potentially via changes in gene expression in the model organism C. elegans.

PubMed

Fischer, Alexandra; Klapper, Maja; Onur, Simone; Menke, Thomas; Niklowitz, Petra; Döring, Frank

2015-05-06

Dietary restriction (DR) is a robust intervention that extends both health span and life span in many organisms. Ubiquinol and ubiquinone represent the reduced and oxidized forms of coenzyme Q (CoQ). CoQ plays a central role in energy metabolism and functions in several cellular processes including gene expression. Here we used the model organism Caenorhabditis elegans to determine level and redox state of CoQ and expression of genes in response to DR. We found that DR down-regulates the steady-state expression levels of several evolutionary conserved genes (i.e. coq-1) that encode key enzymes of the mevalonate and CoQ-synthesizing pathways. In line with this, DR decreases the levels of total CoQ and ubiquinol. This CoQ-reducing effect of DR is obvious in adult worms but not in L4 larvae and is also evident in the eat-2 mutant, a genetic model of DR. In conclusion, we propose that DR reduces the level of CoQ and ubiquinol via gene expression in the model organism C. elegans. © 2015 International Union of Biochemistry and Molecular Biology.

The role of pharmacogenetics and advances in gene therapy in the treatment of diabetic retinopathy.

PubMed

Agarwal, Aniruddha; Ingham, Sally A; Harkins, Keegan A; Do, Diana V; Nguyen, Quan Dong

2016-02-01

Diabetic retinopathy (DR) and its complications such as diabetic macular edema continue to remain a major cause for legal blindness in the developed world. While the introduction of anti-tVEGF agents has significantly improved visual outcomes of patients with DR, unpredictable response, largely due to genetic polymorphisms, appears to be a challenge with this therapy. With advances in identification of various genetic biomarkers, novel therapeutic strategies consisting of gene transfer are being developed and tested for patients with DR. Application of pharmacogenetic principles appears to be a promising futuristic strategy to attenuate diabetes-mediated retinal vasculopathy. In this comprehensive review, data from recent studies in the field of pharmacogenomics for the treatment of DR have been provided.

Validation of automated screening for referable diabetic retinopathy with the IDx-DR device in the Hoorn Diabetes Care System.

PubMed

van der Heijden, Amber A; Abramoff, Michael D; Verbraak, Frank; van Hecke, Manon V; Liem, Albert; Nijpels, Giel

2018-02-01

To increase the efficiency of retinal image grading, algorithms for automated grading have been developed, such as the IDx-DR 2.0 device. We aimed to determine the ability of this device, incorporated in clinical work flow, to detect retinopathy in persons with type 2 diabetes. Retinal images of persons treated by the Hoorn Diabetes Care System (DCS) were graded by the IDx-DR device and independently by three retinal specialists using the International Clinical Diabetic Retinopathy severity scale (ICDR) and EURODIAB criteria. Agreement between specialists was calculated. Results of the IDx-DR device and experts were compared using sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), distinguishing between referable diabetic retinopathy (RDR) and vision-threatening retinopathy (VTDR). Area under the receiver operating characteristic curve (AUC) was calculated. Of the included 1415 persons, 898 (63.5%) had images of sufficient quality according to the experts and the IDx-DR device. Referable diabetic retinopathy (RDR) was diagnosed in 22 persons (2.4%) using EURODIAB and 73 persons (8.1%) using ICDR classification. Specific intergrader agreement ranged from 40% to 61%. Sensitivity, specificity, PPV and NPV of IDx-DR to detect RDR were 91% (95% CI: 0.69-0.98), 84% (95% CI: 0.81-0.86), 12% (95% CI: 0.08-0.18) and 100% (95% CI: 0.99-1.00; EURODIAB) and 68% (95% CI: 0.56-0.79), 86% (95% CI: 0.84-0.88), 30% (95% CI: 0.24-0.38) and 97% (95% CI: 0.95-0.98; ICDR). The AUC was 0.94 (95% CI: 0.88-1.00; EURODIAB) and 0.87 (95% CI: 0.83-0.92; ICDR). For detection of VTDR, sensitivity was lower and specificity was higher compared to RDR. AUC's were comparable. Automated grading using the IDx-DR device for RDR detection is a valid method and can be used in primary care, decreasing the demand on ophthalmologists. © 2017 The Authors. Acta Ophthalmologica published by John Wiley & Sons Ltd on behalf of Acta Ophthalmologica Scandinavica Foundation.

JPRS Report, Near East & South Asia

DTIC Science & Technology

1989-03-09

Sabah al-Ahmad, the committee chairman and Kuwait’s dep- uty prime minister and foreign minister, had a clear and specific visualization of the...Government Because It Has Failed To Solve Our Problems; Union Grouping Member: National Reconciliation Government Is Way Out of Crisis; Pharmacists Union...few days, demanding that the affected unions be given a share in their drafting." Plot To Silence Mouths The head of the Pharmacists ’ Union, Dr

Korean Affairs Report

DTIC Science & Technology

1985-09-11

president of Pyongyang Music and Dance Univers- ity Kim Tong-sop, president of University of Commerce, and academician, Dr and Prof Pak Si-hyong and...investigation of the building. They decided to demand a meeting with the American Ambassador to Korea and a press conference with reporters from both within and...Chong-chin and Sim Yong-chin who at the underground fountain of the Lotte Department Store at the Ulchiro en- trance collected rocks from the nearby

Development of a Subjective Evaluation Tool for Assessing Marksmanship Training Effectiveness

DTIC Science & Technology

2013-01-28

used to break down the marksmanship domain, as presented in the USMC Rifle Marksmanship Manual, into sub-tasks that were converted into training-task... Mangos for his expertise in survey development and, along with Dr. Joseph Chandler, for guidance on the analysis of a complicated data set; Mr. Clarke...alternative to lengthy and resource-demanding training effectiveness evaluations. A task analytic approach was used to break down the marksmanship domain, as

Locating an Imaging Radar in Canada for Identifying Spaceborne Objects

DTIC Science & Technology

1992-12-01

of residents. Daskin (11:48) extended that model to account for the chance that when a demand arrives at the system it will not be covered since all...Journal of Operational Research, 50: 280-297 (February 1991). 11. Daskin , Mark S. " A Maximum Expected Covering Location Model: Formulation...continue with this thesis-, and Dr. William Wiesel for his instruction and help in developing a satellite coordinate frame and understanding the mechanics

Army Business Transformation: The Utility of Using Corporate Business Models within the Institutional Army

DTIC Science & Technology

2007-06-01

Manufacturing by Dr. Robert N. Castellano,3 Essentials of Economics by Damodar Gujarati, New Product Management by Merle Crawford and Anthony Di... Essentials of Economics by Damodar Gujarati, New Product Management by Merle Crawford and Anthony Di Benedetto, Seeing What’s next by Clayton M...attempting to explain how corporations make money. The Essentials of Economics acknowledges that the law of supply and demand is a good model for

Opportunities for Automated Demand Response in California’s Dairy Processing Industry

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

Homan, Gregory K.; Aghajanzadeh, Arian; McKane, Aimee

During periods of peak electrical demand on the energy grid or when there is a shortage of supply, the stability of the grid may be compromised or the cost of supplying electricity may rise dramatically, respectively. Demand response programs are designed to mitigate the severity of these problems and improve reliability by reducing the demand on the grid during such critical times. In 2010, the Demand Response Research Center convened a group of industry experts to suggest potential industries that would be good demand response program candidates for further review. The dairy industry was suggested due to the perception thatmore » the industry had suitable flexibility and automatic controls in place. The purpose of this report is to provide an initial description of the industry with regard to demand response potential, specifically automated demand response. This report qualitatively describes the potential for participation in demand response and automated demand response by dairy processing facilities in California, as well as barriers to widespread participation. The report first describes the magnitude, timing, location, purpose, and manner of energy use. Typical process equipment and controls are discussed, as well as common impediments to participation in demand response and automated demand response programs. Two case studies of demand response at dairy facilities in California and across the country are reviewed. Finally, recommendations are made for future research that can enhance the understanding of demand response potential in this industry.« less

Response to Dr. Moya's Comments to Article by Thoene M et al., Nutrients 2016, 8, 451.

PubMed

Thoene, Melissa; Anderson-Berry, Ann

2016-12-16

This reply is a supplementary addition to our previous article entitled "Comparison of a Powdered, Acidified Liquid, and Non-Acidified Liquid Human Milk Fortifier on Clinical Outcomes in Premature Infants" as published in Nutrients in July 2016. It provides a response to a comment made by Dr. Fernando Moya to this original article, so the purpose of this is to compare and contrast various perspectives between researchers conducting nutrition research in the preterm infant population. It specifically focuses on human milk fortification and subsequent outcomes.

DR-nm23 expression affects neuroblastoma cell differentiation, integrin expression, and adhesion characteristics.

PubMed

Amendola, R; Martinez, R; Negroni, A; Venturelli, D; Tanno, B; Calabretta, B; Raschellà, G

2001-01-01

Nm23 gene family has been associated with metastasis suppression and differentiation. We studied DR-nm23 during neuroblastoma cells differentiation. DR-nm23 expression increased after retinoic acid induction of differentiation in human cell lines SK-N-SH and LAN-5. In several cell lines, overexpression of DR-nm23 was associated with more differentiated phenotypes. SK-N-SH cells increased vimentin expression, increased deposition of collagen type IV, modulated integrin expression, and underwent growth arrest; the murine neuroblastoma cell line N1E-115 showed neurite outgrowth and a striking enhancement of beta1 integrin expression. Up-regulation of beta1 integrin was specifically responsible for the increase in the adhesion to collagen type I-coated plates. Finally, cells overexpressing DR-nm23 were unable to growth in soft agar. In conclusion, DR-nm23 expression is directly involved in differentiation of neuroblastoma cells, and its ability to affects the adhesion to extracellular substrates and to inhibit growth in soft agar suggests an involvement in the metastatic potential of neuroblastoma.

76 FR 11526 - In the Matter of Dr. Gary Kao; Order Prohibiting Involvement In NRC-Licensed Activities

Federal Register 2010, 2011, 2012, 2013, 2014

2011-03-02

... patients until December 2007. In response to the reported medical events, the VA National Health Physics... health or to minimize the danger to life or property in compliance with the Commission's requirements. Therefore, the public health, safety and interest require that Dr. Kao be prohibited from any involvement in...

77 FR 9724 - Request for Petitions To Modify the Rules of Origin Under the Dominican Republic-Central America...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-17

... ministerial-level body responsible for supervising the implementation of the CAFTA-DR, agreed to consider... appropriate. Section 203(o)(3) of the Act authorizes the President to proclaim modifications to the CAFTA-DR...; and (3) the level and breadth of interest that manufacturers, processors, traders, and consumers in...

Why We Do Not Have Ethical Conduct: A Response to Dr. Sternberg

ERIC Educational Resources Information Center

Carson, Jamin

2014-01-01

In "We Need to Teach for Ethical Conduct," Dr. Robert Sternberg argued that students act unethically because they are unable to transfer principles of ethics into practice. While I agree that this is partially the case, it is also the case that unethical behavior is a result of the prevailing educational-philosophy: radical…

"The Butter Battle Book": Engaging Children's Thoughts of War.

ERIC Educational Resources Information Center

Barone, Diane

1993-01-01

Discusses how "The Butter Battle Book" by Dr. Seuss can be used to introduce the moral issue of war to young children. Studies the written responses of 1,187 children in grades kindergarten to 6 to the story. Notes that only the fourth- through sixth-grade students (who felt themselves beyond Dr. Seuss) understood the allegorical nature…

Drivers for the Value of Demand Response under Increased Levels of Wind and Solar Power; NREL (National Renewable Energy Laboratory)

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

Hale, Elaine

Demand response may be a valuable flexible resource for low-carbon electric power grids. However, there are as many types of possible demand response as there are ways to use electricity, making demand response difficult to study at scale in realistic settings. This talk reviews our state of knowledge regarding the potential value of demand response in several example systems as a function of increasing levels of wind and solar power, sometimes drawing on the analogy between demand response and storage. Overall, we find demand response to be promising, but its potential value is very system dependent. Furthermore, demand response, likemore » storage, can easily saturate ancillary service markets.« less

Knowledge, Attitude, and Perception of Barriers for Eye Care among Diabetic Persons Registered at Employee Health Department of a Tertiary Eye Hospital of Central Saudi Arabia.

PubMed

Al-Alawi, Abeer; Al-Hassan, Arif; Chauhan, Deepti; Al-Futais, Muneera; Khandekar, Rajiv

2016-01-01

To evaluate the level of knowledge, attitudes, and barriers to diabetic retinopathy (DR) screening among diabetic healthcare staff at a tertiary eye hospital in central Saudi Arabia. This was a descriptive survey using a closed-ended questionnaire. A. 5-grade. Likert scale was used for responses to each question. Data were collected on patient demographics and the status of diabetes. Survey responses related to knowledge, attitude, and barriers were grouped. The study sample was comprised of 45 diabetics employed at the hospital. The mean age was 49 ± 11 years and 33 diabetics were males. One-third of the study population was referred to the eye clinic for DR screening. DR screening was performed in 25% of diabetics over the previous year. Twenty-nine (64%; 95% confidence intervals: 50-78) participants had excellent knowledge of eyecare for diabetic complications. Thirteen percent of participants had a positive attitude toward periodic eye checkups. Travel distance to an eyecare unit, no referral from family physicians for annual eye checkups and the lack of availability of gender-specific eyecare professionals were the main perceived barriers. Annual DR screening needs to be promoted to primary healthcare providers and diabetic patients. Barriers should be addressed to improve the uptake of DR screening.

Knowledge, Attitude, and Perception of Barriers for Eye Care among Diabetic Persons Registered at Employee Health Department of a Tertiary Eye Hospital of Central Saudi Arabia

PubMed Central

Al-Alawi, Abeer; Al-Hassan, Arif; Chauhan, Deepti; Al-Futais, Muneera; Khandekar, Rajiv

2016-01-01

Purpose: To evaluate the level of knowledge, attitudes, and barriers to diabetic retinopathy (DR) screening among diabetic healthcare staff at a tertiary eye hospital in central Saudi Arabia. Methods: This was a descriptive survey using a closed-ended questionnaire. A. 5-grade. Likert scale was used for responses to each question. Data were collected on patient demographics and the status of diabetes. Survey responses related to knowledge, attitude, and barriers were grouped. Results: The study sample was comprised of 45 diabetics employed at the hospital. The mean age was 49 ± 11 years and 33 diabetics were males. One-third of the study population was referred to the eye clinic for DR screening. DR screening was performed in 25% of diabetics over the previous year. Twenty-nine (64%; 95% confidence intervals: 50–78) participants had excellent knowledge of eyecare for diabetic complications. Thirteen percent of participants had a positive attitude toward periodic eye checkups. Travel distance to an eyecare unit, no referral from family physicians for annual eye checkups and the lack of availability of gender-specific eyecare professionals were the main perceived barriers. Conclusion: Annual DR screening needs to be promoted to primary healthcare providers and diabetic patients. Barriers should be addressed to improve the uptake of DR screening. PMID:26957842

Issues in Differential Response

ERIC Educational Resources Information Center

Hughes, Ronald C.; Rycus, Judith S.; Saunders-Adams, Stacey M.; Hughes, Laura K.; Hughes, Kelli N.

2013-01-01

Differential response (DR), also referred to as alternative response (AR), family assessment response (FAR), or multiple track response, was developed to incorporate family-centered, strengths-based practices into child protective services (CPS), primarily by diverting lower risk families into an assessment track rather than requiring the…

Opportunities for Automated Demand Response in California Agricultural Irrigation

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

Olsen, Daniel; Aghajanzadeh, Arian; McKane, Aimee

Pumping water for agricultural irrigation represents a significant share of California’s annual electricity use and peak demand. It also represents a large source of potential flexibility, as farms possess a form of storage in their wetted soil. By carefully modifying their irrigation schedules, growers can participate in demand response without adverse effects on their crops. This report describes the potential for participation in demand response and automated demand response by agricultural irrigators in California, as well as barriers to widespread participation. The report first describes the magnitude, timing, location, purpose, and manner of energy use in California. Typical on-­farm controlsmore » are discussed, as well as common impediments to participation in demand response and automated demand response programs. Case studies of demand response programs in California and across the country are reviewed, and their results along with overall California demand estimates are used to estimate statewide demand response potential. Finally, recommendations are made for future research that can enhance the understanding of demand response potential in this industry.« less

Genomics, molecular imaging, bioinformatics, and bio-nano-info integration are synergistic components of translational medicine and personalized healthcare research.

PubMed

Yang, Jack Y; Yang, Mary Qu; Arabnia, Hamid R; Deng, Youping

2008-09-16

Supported by National Science Foundation (NSF), International Society of Intelligent Biological Medicine (ISIBM), International Journal of Computational Biology and Drug Design and International Journal of Functional Informatics and Personalized Medicine, IEEE 7th Bioinformatics and Bioengineering attracted more than 600 papers and 500 researchers and medical doctors. It was the only synergistic inter/multidisciplinary IEEE conference with 24 Keynote Lectures, 7 Tutorials, 5 Cutting-Edge Research Workshops and 32 Scientific Sessions including 11 Special Research Interest Sessions that were designed dynamically at Harvard in response to the current research trends and advances. The committee was very grateful for the IEEE Plenary Keynote Lectures given by: Dr. A. Keith Dunker (Indiana), Dr. Jun Liu (Harvard), Dr. Brian Athey (Michigan), Dr. Mark Borodovsky (Georgia Tech and President of ISIBM), Dr. Hamid Arabnia (Georgia and Vice-President of ISIBM), Dr. Ruzena Bajcsy (Berkeley and Member of United States National Academy of Engineering and Member of United States Institute of Medicine of the National Academies), Dr. Mary Yang (United States National Institutes of Health and Oak Ridge, DOE), Dr. Chih-Ming Ho (UCLA and Member of United States National Academy of Engineering and Academician of Academia Sinica), Dr. Andy Baxevanis (United States National Institutes of Health), Dr. Arif Ghafoor (Purdue), Dr. John Quackenbush (Harvard), Dr. Eric Jakobsson (UIUC), Dr. Vladimir Uversky (Indiana), Dr. Laura Elnitski (United States National Institutes of Health) and other world-class scientific leaders. The Harvard meeting was a large academic event 100% full-sponsored by IEEE financially and academically. After a rigorous peer-review process, the committee selected 27 high-quality research papers from 600 submissions. The committee is grateful for contributions from keynote speakers Dr. Russ Altman (IEEE BIBM conference keynote lecturer on combining simulation and machine learning to recognize function in 4D), Dr. Mary Qu Yang (IEEE BIBM workshop keynote lecturer on new initiatives of detecting microscopic disease using machine learning and molecular biology, http://ieeexplore.ieee.org/servlet/opac?punumber=4425386) and Dr. Jack Y. Yang (IEEE BIBM workshop keynote lecturer on data mining and knowledge discovery in translational medicine) from the first IEEE Computer Society BioInformatics and BioMedicine (IEEE BIBM) international conference and workshops, November 2-4, 2007, Silicon Valley, California, USA.

Genomics, molecular imaging, bioinformatics, and bio-nano-info integration are synergistic components of translational medicine and personalized healthcare research

PubMed Central

2008-01-01

Supported by National Science Foundation (NSF), International Society of Intelligent Biological Medicine (ISIBM), International Journal of Computational Biology and Drug Design and International Journal of Functional Informatics and Personalized Medicine, IEEE 7th Bioinformatics and Bioengineering attracted more than 600 papers and 500 researchers and medical doctors. It was the only synergistic inter/multidisciplinary IEEE conference with 24 Keynote Lectures, 7 Tutorials, 5 Cutting-Edge Research Workshops and 32 Scientific Sessions including 11 Special Research Interest Sessions that were designed dynamically at Harvard in response to the current research trends and advances. The committee was very grateful for the IEEE Plenary Keynote Lectures given by: Dr. A. Keith Dunker (Indiana), Dr. Jun Liu (Harvard), Dr. Brian Athey (Michigan), Dr. Mark Borodovsky (Georgia Tech and President of ISIBM), Dr. Hamid Arabnia (Georgia and Vice-President of ISIBM), Dr. Ruzena Bajcsy (Berkeley and Member of United States National Academy of Engineering and Member of United States Institute of Medicine of the National Academies), Dr. Mary Yang (United States National Institutes of Health and Oak Ridge, DOE), Dr. Chih-Ming Ho (UCLA and Member of United States National Academy of Engineering and Academician of Academia Sinica), Dr. Andy Baxevanis (United States National Institutes of Health), Dr. Arif Ghafoor (Purdue), Dr. John Quackenbush (Harvard), Dr. Eric Jakobsson (UIUC), Dr. Vladimir Uversky (Indiana), Dr. Laura Elnitski (United States National Institutes of Health) and other world-class scientific leaders. The Harvard meeting was a large academic event 100% full-sponsored by IEEE financially and academically. After a rigorous peer-review process, the committee selected 27 high-quality research papers from 600 submissions. The committee is grateful for contributions from keynote speakers Dr. Russ Altman (IEEE BIBM conference keynote lecturer on combining simulation and machine learning to recognize function in 4D), Dr. Mary Qu Yang (IEEE BIBM workshop keynote lecturer on new initiatives of detecting microscopic disease using machine learning and molecular biology, http://ieeexplore.ieee.org/servlet/opac?punumber=4425386) and Dr. Jack Y. Yang (IEEE BIBM workshop keynote lecturer on data mining and knowledge discovery in translational medicine) from the first IEEE Computer Society BioInformatics and BioMedicine (IEEE BIBM) international conference and workshops, November 2-4, 2007, Silicon Valley, California, USA. PMID:18831773

Dr.LiTHO: a development and research lithography simulator

NASA Astrophysics Data System (ADS)

Fühner, Tim; Schnattinger, Thomas; Ardelean, Gheorghe; Erdmann, Andreas

2007-03-01

This paper introduces Dr.LiTHO, a research and development oriented lithography simulation environment developed at Fraunhofer IISB to flexibly integrate our simulation models into one coherent platform. We propose a light-weight approach to a lithography simulation environment: The use of a scripting (batch) language as an integration platform. Out of the great variety of different scripting languages, Python proved superior in many ways: It exhibits a good-natured learning-curve, it is efficient, available on virtually any platform, and provides sophisticated integration mechanisms for existing programs. In this paper, we will describe the steps, required to provide Python bindings for existing programs and to finally generate an integrated simulation environment. In addition, we will give a short introduction into selected software design demands associated with the development of such a framework. We will especially focus on testing and (both technical and user-oriented) documentation issues. Dr.LiTHO Python files contain not only all simulation parameter settings but also the simulation flow, providing maximum flexibility. In addition to relatively simple batch jobs, repetitive tasks can be pooled in libraries. And as Python is a full-blown programming language, users can add virtually any functionality, which is especially useful in the scope of simulation studies or optimization tasks, that often require masses of evaluations. Furthermore, we will give a short overview of the numerous existing Python packages. Several examples demonstrate the feasibility and productiveness of integrating Python packages into custom Dr.LiTHO scripts.

Epigenetic mechanisms of dietary restriction induced aging in Drosophila.

PubMed

Lian, Ting; Gaur, Uma; Yang, Deying; Li, Diyan; Li, Ying; Yang, Mingyao

2015-12-01

Aging is a long-standing problem that people are always interested in. Thus, it is critical to understand the underlying molecular mechanisms in aging and explore the most efficient method to extend life expectancy. To achieve this goal, a wide range of systems including cells, rodent models, budding yeast, worms and flies have been employed for decades. In recent years, the effect of dietary restriction (DR) on lifespan is in the prime focus. Although we have confirmed that reduced insulin and/or insulin-like growth factor (IGF) and the target of rapamycin (TOR) signaling can increase Drosophila lifespan; the precise molecular mechanisms and nutritional response landscape of diet-mediated aging is ambiguous. Epigenetic events have been considered as the major contributors to lifespan extension with response to DR. The role of DNA methylation in aging is well acknowledged in mammals and rodents where it has been shown to impact aging by regulating the transcription, though the mechanism of regulation is not limited to only transcription. In Drosophila, the contribution of methylation during DR in aging is definitely less explored. In this review, we will update the advances in mechanisms of DR, with a particular focus on methylation as an upcoming target for aging studies and discuss Drosophila as a powerful model to understand mechanisms of aging with response to diet. Copyright © 2015 Elsevier Inc. All rights reserved.

Granuloma Encapsulation Is a Key Factor for Containing Tuberculosis Infection in Minipigs

PubMed Central

Vilaplana, Cristina; Tapia, Gustavo; Díaz, Jorge; Fort, María; Cáceres, Neus; Pinto, Sergio; Caylà, Joan; Corner, Leigh; Domingo, Mariano; Cardona, Pere-Joan

2010-01-01

A transthoracic infection involving a low dose of Mycobacterium tuberculosis has been used to establish a new model of infection in minipigs. The 20-week monitoring period showed a marked Th1 response and poor humoral response for the whole infection. A detailed histopathological analysis was performed after slicing the formalin-fixed whole lungs of each animal. All lesions were recorded and classified according to their microscopic aspect, their relationship with the intralobular connective network and their degree of maturity in order to obtain a dissemination ratio (DR) between recent and old lesions. CFU counts and evolution of the DR with time showed that the proposed model correlated with a contained infection, decreasing from week 9 onwards. These findings suggest that the infection induces an initial Th1 response, which is followed by local fibrosis and encapsulation of the granulomas, thereby decreasing the onset of new lesions. Two therapeutic strategies were applied in order to understand how they could influence the model. Thus, chemotherapy with isoniazid alone helped to decrease the total number of lesions, despite the increase in DR after week 9, with similar kinetics to those of the control group, whereas addition of a therapeutic M. tuberculosis fragment-based vaccine after chemotherapy increased the Th1 and humoral responses, as well as the number of lesions, but decreased the DR. By providing a local pulmonary structure similar to that in humans, the mini-pig model highlights new aspects that could be key to a better understanding tuberculosis infection control in humans. PMID:20386605

Granuloma encapsulation is a key factor for containing tuberculosis infection in minipigs.

PubMed

Gil, Olga; Díaz, Ivan; Vilaplana, Cristina; Tapia, Gustavo; Díaz, Jorge; Fort, María; Cáceres, Neus; Pinto, Sergio; Caylà, Joan; Corner, Leigh; Domingo, Mariano; Cardona, Pere-Joan

2010-04-06

A transthoracic infection involving a low dose of Mycobacterium tuberculosis has been used to establish a new model of infection in minipigs. The 20-week monitoring period showed a marked Th1 response and poor humoral response for the whole infection. A detailed histopathological analysis was performed after slicing the formalin-fixed whole lungs of each animal. All lesions were recorded and classified according to their microscopic aspect, their relationship with the intralobular connective network and their degree of maturity in order to obtain a dissemination ratio (DR) between recent and old lesions. CFU counts and evolution of the DR with time showed that the proposed model correlated with a contained infection, decreasing from week 9 onwards. These findings suggest that the infection induces an initial Th1 response, which is followed by local fibrosis and encapsulation of the granulomas, thereby decreasing the onset of new lesions. Two therapeutic strategies were applied in order to understand how they could influence the model. Thus, chemotherapy with isoniazid alone helped to decrease the total number of lesions, despite the increase in DR after week 9, with similar kinetics to those of the control group, whereas addition of a therapeutic M. tuberculosis fragment-based vaccine after chemotherapy increased the Th1 and humoral responses, as well as the number of lesions, but decreased the DR. By providing a local pulmonary structure similar to that in humans, the mini-pig model highlights new aspects that could be key to a better understanding tuberculosis infection control in humans.

DR3 regulation of apoptosis of naive T-lymphocytes in children with acute infectious mononucleosis.

PubMed

Filatova, Elena Nikolaevna; Anisenkova, Elena Viktorovna; Presnyakova, Nataliya Borisovna; Utkin, Oleg Vladimirovich

2016-09-01

Acute infectious mononucleosis (AIM) is a widespread viral disease that mostly affects children. Development of AIM is accompanied by a change in the ratio of immune cells. This is provided by means of different biological processes including the regulation of apoptosis of naive T-cells. One of the potential regulators of apoptosis of T-lymphocytes is a death receptor 3 (DR3). We have studied the role of DR3 in the regulation of apoptosis of naive CD4 + (nTh) and CD8 + (nCTL) T-cells in healthy children and children with AIM. In healthy children as well as in children with AIM, the activation of DR3 is accompanied by inhibition of apoptosis of nTh. In healthy children, the stimulation of DR3 resulted in the increase in apoptosis of nCTL. On the contrary, in children with AIM, the level of apoptosis of nCTL decreased after DR3 activation, which is a positive contribution to the antiviral immune response. In children with AIM, nCTL are characterized by reduced level of apoptosis as compared with healthy children. These results indicate that DR3 can be involved in the reduction of sensitivity of nCTL to apoptosis in children with AIM.

Effects of dietary restriction on the expression of insulin-signaling-related genes in long-lived mutant mice.

PubMed

Bartke, Andrzej; Masternak, Michal M; Al-Regaiey, Khalid A; Bonkowski, Michael S

2007-01-01

Hypopituitary Ames dwarf mice and growth-hormone-resistant (growth hormone receptor knockout, GHRKO) mice have reduced plasma levels of insulin-like growth factor 1 and insulin, enhanced insulin sensitivity and a remarkably increased life span. This resembles the phenotypic characteristics of genetically normal animals subjected to dietary restriction (DR). Interestingly, DR leads to further increases in insulin sensitivity and longevity in Ames dwarfs but not in GHRKO mice. It was therefore of interest to examine the effects of DR on the expression of insulin-related genes in these two types of long-lived mutant mice. The effects of DR partially overlapped but did not duplicate the effects of Ames dwarfism or GHR deletion on the expression of genes related to insulin signaling and cell responsiveness to insulin. Moreover, the effects of DR on the expression of the examined genes in different insulin target organs were not identical. Some of the insulin-related genes were similarly affected by DR in both GHRKO and normal mice, some were affected only in GHRKO mice and some only in normal animals. This last category is of particular interest since genes affected in normal but not GHRKO mice may be related to mechanisms by which DR extends longevity.

Energy Efficiency and Demand Response for Residential Applications

NASA Astrophysics Data System (ADS)

Wellons, Christopher J., II

The purpose of this thesis is to analyze the costs, feasibility and benefits of implementing energy efficient devices and demand response programs to a residential consumer environment. Energy efficiency and demand response are important for many reasons, including grid stabilization. With energy demand increasing, as the years' pass, the drain on the grid is going up. There are two key solutions to this problem, increasing supply by building more power plants and decreasing demand during peak periods, by increasing participation in demand response programs and by upgrading residential and commercial customers to energy efficient devices, to lower demand throughout the day. This thesis focuses on utilizing demand response methods and energy efficient device to reduce demand. Four simulations were created to analyze these methods. These simulations show the importance of energy efficiency and demand response participation to help stabilize the grid, integrate more alternative energy resources, and reduce emissions from fossil fuel generating facilities. The results of these numerical analyses show that demand response and energy efficiency can be beneficial to consumers and utilities. With demand response being the most beneficial to the utility and energy efficiency, specifically LED lighting, providing the most benefits to the consumer.

Gaia DR2 documentation Chapter 1: Introduction

NASA Astrophysics Data System (ADS)

de Bruijne, J. H. J.; Abreu, A.; Brown, A. G. A.; Castañeda, J.; Cheek, N.; Crowley, C.; De Angeli, F.; Drimmel, R.; Fabricius, C.; Fleitas, J.; Gracia-Abril, G.; Guerra, R.; Hutton, A.; Messineo, R.; Mora, A.; Nienartowicz, K.; Panem, C.; Siddiqui, H.

2018-04-01

This chapter of the Gaia DR2 documentation describes the Gaia mission, the Gaia spacecraft, and the organisation of the Gaia Data Processing and Analysis Consortium (DPAC), which is responsible for the processing and analysis of the Gaia data. Furthermore, various properties of the data release are summarised, including statistical properties, object statistics, completeness, selection and filtering criteria, and limitations of the data.

Response to Lessinger: The Great Day of Judgment.

ERIC Educational Resources Information Center

Bhaerman, Bob

Dr. Lessinger's position of accountability (see ED040 155) seems to be within a very limited view of the function of the school. Not all educators are well adjusted to the status quo; some hold that the school shall build a new social order. Dr. Lessinger seems to say that teachers should be accountable for the training component but not the more…

The Importance of What You Leave Behind: A Conversation with Carl Smith

ERIC Educational Resources Information Center

Teagarden, Jim; Zabel, Robert; Kaff, Marilyn

2017-01-01

Dr. Carl Smith shares his reflections on a varied career that included many different roles and responsibilities but shared a focus on children with behavior disorders. Dr. Smith also provides insight into where he believes the field is heading and offers his advice to those just entering the field. Perhaps the lasting advice to all is to focus on…

Response to Paper III Economics in the Civics Curriculum. A Reaction to Andrew F. Brimmer.

ERIC Educational Resources Information Center

Schug, Mark C.

According to the document, Dr. Andrew Brimmer did an excellent job of identifying emerging economic concerns. Dr. Brimmer's characterization of economics as a tool kit can help young people examine important social questions using principles of economics as the tool for analysis. One way to build an economics tool kit is by placing more stress on…

Glucose Deprivation Induces ATF4-Mediated Apoptosis through TRAIL Death Receptors

PubMed Central

Iurlaro, Raffaella; Püschel, Franziska; León-Annicchiarico, Clara Lucía; O'Connor, Hazel; Martin, Seamus J.; Palou-Gramón, Daniel; Lucendo, Estefanía

2017-01-01

ABSTRACT Metabolic stress occurs frequently in tumors and in normal tissues undergoing transient ischemia. Nutrient deprivation triggers, among many potential cell death-inducing pathways, an endoplasmic reticulum (ER) stress response with the induction of the integrated stress response transcription factor ATF4. However, how this results in cell death remains unknown. Here we show that glucose deprivation triggered ER stress and induced the unfolded protein response transcription factors ATF4 and CHOP. This was associated with the nontranscriptional accumulation of TRAIL receptor 1 (TRAIL-R1) (DR4) and with the ATF4-mediated, CHOP-independent induction of TRAIL-R2 (DR5), suggesting that cell death in this context may involve death receptor signaling. Consistent with this, the ablation of TRAIL-R1, TRAIL-R2, FADD, Bid, and caspase-8 attenuated cell death, although the downregulation of TRAIL did not, suggesting ligand-independent activation of TRAIL receptors. These data indicate that stress triggered by glucose deprivation promotes the ATF4-dependent upregulation of TRAIL-R2/DR5 and TRAIL receptor-mediated cell death. PMID:28242652

Nanoarchitectured electrochemical cytosensors for selective detection of leukemia cells and quantitative evaluation of death receptor expression on cell surfaces.

PubMed

Zheng, Tingting; Fu, Jia-Ju; Hu, Lihui; Qiu, Fan; Hu, Minjin; Zhu, Jun-Jie; Hua, Zi-Chun; Wang, Hui

2013-06-04

The variable susceptibility to the tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) treatment observed in various types of leukemia cells is related to the difference in the expression levels of death receptors, DR4 and DR5, on the cell surfaces. Quantifying the DR4/DR5 expression status on leukemia cell surfaces is of vital importance to the development of diagnostic tools to guide death receptor-based leukemia treatment. Taking the full advantages of novel nanobiotechnology, we have developed a robust electrochemical cytosensing approach toward ultrasensitive detection of leukemia cells with detection limit as low as ~40 cells and quantitative evaluation of DR4/DR5 expression on leukemia cell surfaces. The optimization of electron transfer and cell capture processes at specifically tailored nanobiointerfaces and the incorporation of multiple functions into rationally designed nanoprobes provide unique opportunities of integrating high specificity and signal amplification on one electrochemical cytosensor. The high sensitivity and selectivity of this electrochemical cytosensing approach also allows us to evaluate the dynamic alteration of DR4/DR5 expression on the surfaces of living cells in response to drug treatments. Using the TRAIL-resistant HL-60 cells and TRAIL-sensitive Jurkat cells as model cells, we have further verified that the TRAIL susceptibility of various types of leukemia cells is directly correlated to the surface expression levels of DR4/DR5. This versatile electrochemical cytosensing platform is believed to be of great clinical value for the early diagnosis of human leukemia and the evaluation of therapeutic effects on leukemia patients after radiation therapy or drug treatment.

Social stress alters inhibitory synaptic input to distinct subpopulations of raphe serotonin neurons.

PubMed

Crawford, LaTasha K; Rahman, Shumaia F; Beck, Sheryl G

2013-01-16

Anxiety disorders are among the most prevalent psychiatric disorders, yet much is unknown about the underlying mechanisms. The dorsal raphe (DR) is at the crux of the anxiety-inducing effects of uncontrollable stress, a key component of models of anxiety. Though DR serotonin (5-HT) neurons play a prominent role, anxiety-associated changes in the physiology of 5-HT neurons remain poorly understood. A 5-day social defeat model of anxiety produced a multifaceted, anxious phenotype in intruder mice that included increased avoidance behavior in the open field test, increased stress-evoked grooming, and increased bladder and heart weights when compared to control mice. Intruders were further compared to controls using electrophysiology recordings conducted in midbrain slices wherein recordings targeted 5-HT neurons of the ventromedial (vmDR) and lateral wing (lwDR) subfields of the DR. Though defining membrane characteristics of 5-HT neurons were unchanged, γ-aminobutyric-acid-mediated (GABAergic) synaptic regulation of 5-HT neurons was altered in a topographically specific way. In the vmDR of intruders, there was a decrease in the frequency and amplitude of GABAergic spontaneous inhibitory postsynaptic currents (sIPSCs). However, in the lwDR, there was an increase in the strength of inhibitory signals due to slower sIPSC kinetics. Synaptic changes were selective for GABAergic input, as glutamatergic synaptic input was unchanged in intruders. The distinct inhibitory regulation of DR subfields provides a mechanism for increased 5-HT output in vmDR target regions and decreased 5-HT output in lwDR target regions, divergent responses to uncontrollable stress that have been reported in the literature but were previously poorly understood.

BCL-2 system analysis identifies high-risk colorectal cancer patients.

PubMed

Lindner, Andreas U; Salvucci, Manuela; Morgan, Clare; Monsefi, Naser; Resler, Alexa J; Cremona, Mattia; Curry, Sarah; Toomey, Sinead; O'Byrne, Robert; Bacon, Orna; Stühler, Michael; Flanagan, Lorna; Wilson, Richard; Johnston, Patrick G; Salto-Tellez, Manuel; Camilleri-Broët, Sophie; McNamara, Deborah A; Kay, Elaine W; Hennessy, Bryan T; Laurent-Puig, Pierre; Van Schaeybroeck, Sandra; Prehn, Jochen H M

2017-12-01

The mitochondrial apoptosis pathway is controlled by an interaction of multiple BCL-2 family proteins, and plays a key role in tumour progression and therapy responses. We assessed the prognostic potential of an experimentally validated, mathematical model of BCL-2 protein interactions (DR_MOMP) in patients with stage III colorectal cancer (CRC). Absolute protein levels of BCL-2 family proteins were determined in primary CRC tumours collected from n=128 resected and chemotherapy-treated patients with stage III CRC. We applied DR_MOMP to categorise patients as high or low risk based on model outputs, and compared model outputs with known prognostic factors (T-stage, N-stage, lymphovascular invasion). DR_MOMP signatures were validated on protein of n=156 patients with CRC from the Cancer Genome Atlas (TCGA) project. High-risk stage III patients identified by DR_MOMP had an approximately fivefold increased risk of death compared with patients identified as low risk (HR 5.2, 95% CI 1.4 to 17.9, p=0.02). The DR_MOMP signature ranked highest among all molecular and pathological features analysed. The prognostic signature was validated in the TCGA colon adenocarcinoma (COAD) cohort (HR 4.2, 95% CI 1.1 to 15.6, p=0.04). DR_MOMP also further stratified patients identified by supervised gene expression risk scores into low-risk and high-risk categories. BCL-2-dependent signalling critically contributed to treatment responses in consensus molecular subtypes 1 and 3, linking for the first time specific molecular subtypes to apoptosis signalling. DR_MOMP delivers a system-based biomarker with significant potential as a prognostic tool for stage III CRC that significantly improves established histopathological risk factors. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Two subsets of HLA-DQA1 alleles mark phenotypic variation in levels of insulin autoantibodies in first degree relatives at risk for insulin-dependent diabetes.

PubMed Central

Pugliese, A; Bugawan, T; Moromisato, R; Awdeh, Z L; Alper, C A; Jackson, R A; Erlich, H A; Eisenbarth, G S

1994-01-01

Levels of insulin autoantibodies (IAA) vary among different first degree relatives of insulin-dependent diabetes mellitus patients, suggesting genetic regulation. We previously reported elevated IAA among DR4-positive at risk relatives. In this study, 72/82 at risk relatives were IAA positive, of whom 75% (54/72) carried DR4 versus 20% (2/10) of IAA-negative relatives (P = 0.0004). However, 69% (18/26) of DR4-negative relatives were IAA positive. Since DR4 did not account for all IAA positivity, we analyzed DQA1 and DQB1 alleles. Homozygosity for DQA1 alleles deriving from the evolutionary lineage 4 (*0401, *0501, *0601) was associated with low IAA levels, while lineage 1-3 alleles (*0101, *0102, *0103, *0201, *0301) correlated with higher levels. Most (93%, 65/70) relatives with lineage 1-3 alleles were IAA positive (mean = 360 +/- 63 SEM nU/ml). Only 7/12 relatives homozygous for lineage 4 alleles were IAA-positive, with lower levels than relatives with lineage 1-3 alleles (mean = 55 +/- 15 SEM nU/ml, P < 0.0001; 7/12 vs 65/70, P = 0.004). The amino acid sequences of lineage 1-3 alleles uniquely share glutamic acid (E) and phenylalanine (F) at positions 40 and 51 (EF alleles). Lineage 4 alleles have glycine (G) and leucine (L) at those positions (GL alleles). 90% (65/72) of IAA-positive relatives had an EF allele, while only 75% (54/72) had DR4 (P = 0.01). Homozygosity for GL alleles (often DQA1 *0501 on DR3 haplotypes) correlated with little or no humoral response to insulin. Thus, HLA-DQB1 GL alleles, or other genes on haplotypes (e.g., DR3) that carry these DQA1 alleles, may confer recessive low responsiveness to insulin. PMID:8200980

Near East/South Asia Report, No. 2702

DTIC Science & Technology

1983-02-03

8217--disagreement centered on that word--representative of the Palestinian people. Dr Ibrahim pointed out a number of other occasions during the fall when...much in demand on the world market: the substance in ques- tion is DAP (diammonium phosphate). And though the new ICM 3 plant will make it possible...Fertilizers" plant, by the construction of a new production unit for DAP and NPK [expansion unknown], made from the acid produced on site, imported ammonia

Crosstalk: The Journal of Defense Software Engineering. Volume 22, Number 4

DTIC Science & Technology

2009-06-01

ORGANIZATION REPORT NUMBER 9. SPONSORING/MONITORING AGENCY NAME(S) AND ADDRESS(ES) 10 . SPONSOR/MONITOR’S ACRONYM(S) 11. SPONSOR/MONITOR’S REPORT NUMBER...collaborate and produce quality results on a DoD project. by Dr. William R. Nichols, Anita D. Carleton, Watts S. Humphrey, and James W. Over Measuring...through both demanding software customers—and my own com- plaints during two- minute waits at the drive-thru window. Sometimes we just can- not get things

Cooling Requirements for the Ultra-Compact Combustor

DTIC Science & Technology

2012-03-01

Sir Frank Whittle and Dr. Hans von Ohain introduced the turbojet con- cept in the 1940’s, turbine engines have become an integral part in aviation com...munity and is the major propulsion system in modern aviation . Since the birth of turbine engines , the demand to expand the power output of the... turbine engine has in- creased. Over the past six decades, both civilian and military efforts have been made in achieving higher thrust out of aircraft

Synthetic Fuels and Biofuels: Questionable Replacements for Petroleum

DTIC Science & Technology

2008-12-31

Hardy, D.R. Biodiesels fuels: Use of Soy Oil as a Blending Stock for Middle Distillate Petroleum Fuels. Ind. Eng. Chem. Res. 2000, 39(10), 3945...BACKGROUND The world market supply of oil along with growing environmental concerns has led to an increase demand in production of biodiesel...which differs from the ASTM D975-06 specification for diesel fuel oils as shown in Table 1 [8,9], in addition to key property requirements that are

Homozygous parent affected sib pair method for detecting disease predisposing variants: application to insulin dependent diabetes mellitus.

PubMed

Robinson, W P; Barbosa, J; Rich, S S; Thomson, G

1993-01-01

For complex genetic diseases involving incomplete penetrance, genetic heterogeneity, and multiple disease genes, it is often difficult to determine the molecular variant(s) responsible for the disease pathogenesis. Linkage and association studies may help identify genetic regions and molecular variants suspected of being directly responsible for disease predisposition or protection, but, especially for complex diseases, they are less useful for determining when a predisposing molecular variant has been identified. In this paper, we expand upon the simple concept that if a genetic factor predisposing to disease has been fully identified, then a parent homozygous for this factor should transmit either of his/her copies at random to any affected children. Closely linked markers are used to determine identity by descent values in affected sib pairs from a parent homozygous for a putative disease predisposing factor. The expected deviation of haplotype sharing from 50%, when not all haplotypes carrying this factor are in fact equally predisposing, has been algebraically determined for a single locus general disease model. Equations to determine expected sharing for multiple disease alleles or multiple disease locus models have been formulated. The recessive case is in practice limiting and therefore can be used to estimate the maximum proportion of putative susceptibility haplotypes which are in fact predisposing to disease when the mode of inheritance of a disease is unknown. This method has been applied to 27 DR3/DR3 parents and 50 DR4/DR4 parents who have at least 2 children affected with insulin dependent diabetes mellitus (IDDM). The transmission of both DR3 and DR4 haplotypes is statistically different from 50% (P < 0.05 and P < 0.001, respectively). An upper estimate for the proportion of DR3 haplotypes associated with a high IDDM susceptibility is 49%, and for DR4 haplotypes 38%. Our results show that the joint presence of non-Asp at DQ beta position 57 and Arg at DQ alpha position 52, which has been proposed as a strong IDDM predisposing factor, is insufficient to explain the HLA component of IDDM predisposition.

Expression of CD 68, CD 45 and human leukocyte antigen-DR in central and peripheral giant cell granuloma, giant cell tumor of long bones, and tuberculous granuloma: An immunohistochemical study.

PubMed

Kumar, Anoop; Sherlin, Herald J; Ramani, Pratibha; Natesan, Anuja; Premkumar, Priya

2015-01-01

Multinucleated giant cells (MNCs) form an integral part of numerous bone and soft tissue tumors, tumor-like lesions and are often associated with granulomas of immunological and nonimmunological origin. The presence of various types of giant cells depends on the lesions in which they are present which are difficult to be diagnosed under routine histological techniques. Immunohistochemistry can be used for a better diagnosis and understanding of the origin of various giant cells using various markers of immune response like human leukocyte antigen-DR (HLA-DR) and those expressed on monocytes and macrophages like CD 68 and leukocyte common antigen (LCA). The study group consisted of 10 cases of giant cell tumor (GCT) of long bones, tuberculous granuloma, and giant cell granuloma to evaluate and analyze the expression pattern of LCA, CD 68, and HLA-DR in various giant cell lesions. Strong expression of CD 68 was observed in 80% of the lesions, strong and moderate expression of CD 45 observed in 70% of the lesions among and within the groups. In contrast, HLA-DR demonstrated negative expression in 80% of cases except for tuberculous granuloma where all the 10 cases showed moderate to strong immunoreactivity. CD 68 and CD 45 expression was found in central giant cell granuloma, peripheral giant cell granuloma and GCT, suggesting the origin from mononuclear phagocyte system and considering their clinical behavior of osteoclast type. High expressivity of HLA-DR in tuberculous granulomas which is an essential factor for presentation of the microbial antigen to CD 4 helper cells thus reassuring the fact that they are up-regulated in response to infection.

[Dr. Moritz Wallach--a century of medicine and tradition in Shaare Zedek].

PubMed

Navot, Orit

2003-06-01

Dr. Wallach, who founded the Shaare Zedek Hospital and managed the institution for forty-five years, was instrumental in providing modern medical care to Jerusalem residents since his arrival in the city in 1891. He dedicated his life to medicine, to the Jerusalem Jewish community, and to improving the quality of service provided by the existing medical establishment. He was one of the outstanding personalities in a city and community struggling for existence. The Jewish religious character that marks today's Shaare Zedek hospital was determined 100 years ago by Dr. Wallach, who integrated the ancient Jewish moral spirit into a modern medical service tradition. While fulfilling his daily tasks, both as a practicing physician and as the hospital-director, Dr. Wallach became a role model to those who followed him. He mixed freely with the "elite" and his personal relations with local dignitaries, political figures, influential westerners, intellectuals, and important foreign diplomats contributed significantly to the growth, success, and reputation the hospital enjoyed during the last century. On the other hand, he was also personally involved with destitute new immigrants to Eretz Israel and actively engaged in finding jobs, housing, and employment for them. Dr. Wallach became a legend in his own time, both locally and internationally. Due to his professional status and personality, Dr. Wallach became a representative of the Jewish community. He had the ability to speak for the Jews with the Ottoman authorities, and afterwards with the British Mandate authorities. He played a significant role in educating the population in public responsibility, while concurrently leaving his mark on generations of physicians who learned from him the value of precision, loyalty, professional secrecy, and medical responsibility. He was one of the "Giants" of the land (Yishuv) in its critical formative years.

Linear-No-Threshold Default Assumptions for Noncancer and Nongenotoxic Cancer Risks: A Mathematical and Biological Critique.

PubMed

Bogen, Kenneth T

2016-03-01

To improve U.S. Environmental Protection Agency (EPA) dose-response (DR) assessments for noncarcinogens and for nonlinear mode of action (MOA) carcinogens, the 2009 NRC Science and Decisions Panel recommended that the adjustment-factor approach traditionally applied to these endpoints should be replaced by a new default assumption that both endpoints have linear-no-threshold (LNT) population-wide DR relationships. The panel claimed this new approach is warranted because population DR is LNT when any new dose adds to a background dose that explains background levels of risk, and/or when there is substantial interindividual heterogeneity in susceptibility in the exposed human population. Mathematically, however, the first claim is either false or effectively meaningless and the second claim is false. Any dose-and population-response relationship that is statistically consistent with an LNT relationship may instead be an additive mixture of just two quasi-threshold DR relationships, which jointly exhibit low-dose S-shaped, quasi-threshold nonlinearity just below the lower end of the observed "linear" dose range. In this case, LNT extrapolation would necessarily overestimate increased risk by increasingly large relative magnitudes at diminishing values of above-background dose. The fact that chemically-induced apoptotic cell death occurs by unambiguously nonlinear, quasi-threshold DR mechanisms is apparent from recent data concerning this quintessential toxicity endpoint. The 2009 NRC Science and Decisions Panel claims and recommendations that default LNT assumptions be applied to DR assessment for noncarcinogens and nonlinear MOA carcinogens are therefore not justified either mathematically or biologically. © 2015 The Author. Risk Analysis published by Wiley Periodicals, Inc. on behalf of Society for Risk Analysis.

Characterization of beta-cell mass and insulin resistance in diet-induced obese and diet-resistant rats.

PubMed

Paulsen, Sarah J; Jelsing, Jacob; Madsen, Andreas N; Hansen, Gitte; Lykkegaard, Kirsten; Larsen, Leif K; Larsen, Philip J; Levin, Barry E; Vrang, Niels

2010-02-01

The selectively bred diet-induced obese (DIO) and diet-resistant (DR) rats represent a polygenetic animal model mimicking most clinical variables characterizing the human metabolic syndrome. When fed a high-energy (HE) diet DIO rats develop visceral obesity, dyslipidemia, hyperinsulinemia, and insulin resistance but never frank diabetes. To improve our understanding of the underlying cause for the deteriorating glucose and insulin parameters, we have investigated possible adaptive responses in DIO and DR rats at the level of the insulin-producing beta-cells. At the time of weaning, DR rats were found to have a higher body weight and beta-cell mass compared to DIO rats, and elevated insulin and glucose responses to an oral glucose load. However, at 2.5 months of age, and for the remaining study period, the effect of genotype became evident: the chow-fed DIO rats steadily increased their body weight and beta-cell mass, as well as insulin and glucose levels compared to the DR rats. HE feeding affected both DIO and DR rats leading to an increased body weight and an increased beta-cell mass. Interestingly, although the beta-cell mass in DR rats and chow-fed DIO rats appeared to constantly increase with age, the beta-cell mass in the HE-fed DIO rats did not continue to do so. This might constitute part of an explanation for their reduced glucose tolerance. Collectively, the data support the use of HE-fed DIO rats as a model of human obesity and insulin resistance, and accentuate its relevance for studies examining the benefit of pharmaceutical compounds targeting this disease complex.

Methylphenidate modulates dorsal raphe neuronal activity: Behavioral and neuronal recordings from adolescent rats.

PubMed

Kharas, Natasha; Whitt, Holly; Reyes-Vasquez, Cruz; Dafny, Nachum

2017-01-01

Methylphenidate (MPD) is a widely prescribed psychostimulants used for the treatment of attention deficit hyperactive disorder (ADHD). Unlike the psychostimulants cocaine and amphetamine, MPD does not exhibit direct actions on the serotonin transporter, however there is evidence suggesting that the therapeutic effects of MPD may be mediated in part by alterations in serotonin transmission. This study aimed to investigate the role of the dorsal raphe (DR) nucleus, one of the major sources of serotonergic innervation in the mammalian brain, in the response to MPD exposure. Freely behaving adolescent rats previously implanted bilaterally with permanent electrodes were used. An open field assay and a wireless neuronal recording system were used to concomitantly record behavioral and DR electrophysiological activity following acute and chronic MPD exposure. Four groups were used: one control (saline) and three experimental groups treated with 0.6, 2.5, and 10.0mg/kg MPD respectively. Animals received daily MPD or saline injections on experimental days 1-6, followed by 3 washout days and MPD rechallenge dose on experimental day (ED)10. The same chronic dose of MPD resulted in either behavioral sensitization or tolerance, and we found that neuronal activity recorded from the DR neuronal units of rats expressing behavioral sensitization to chronic MPD exposure responded significantly differently to MPD rechallenge on ED10 compared to the DR unit activity recorded from animals that expressed behavioral tolerance. This correlation between behavioral response and DR neuronal activity following chronic MPD exposure provides evidence that the DR is involved in the acute effects as well as the chronic effects of MPD in adolescent rats. Copyright © 2016 Elsevier Inc. All rights reserved.

Increased Cyclooxygenase-2-Derived Prostanoids Contributes to the Hyperreactivity to Noradrenaline in Mesenteric Resistance Arteries from Offspring of Diabetic Rats

PubMed Central

Santos-Rocha, Juliana; Duarte, Gloria P.; Xavier, Fabiano E.

2012-01-01

This study analyzed the effect of in utero exposure to maternal diabetes on contraction to noradrenaline in mesenteric resistance arteries (MRA) from adult offspring, focusing on the role of cyclooxygenase (COX)-derived prostanoids. Diabetes in the maternal rat was induced by a single injection of streptozotocin (50 mg/kg body weight) on day 7 of pregnancy. Contraction to noradrenaline was analyzed in isolated MRA from offspring of diabetic (O-DR) and non-diabetic (O-CR) rats at 3, 6 and 12 months of age. Release of thromboxane A2 (TxA2) and prostaglandins E2 (PGE2) and F2α (PGF2α), was measured by specific enzyme immunoassay kits. O-DR developed hypertension from 6 months of age compared with O-CR. Arteries from O-DR were hyperactive to noradrenaline only at 6 and 12 months of age. Endothelial removal abolished this hyperreactivity to noradrenaline between O-CR and O-DR. Preincubation with either the COX-1/2 (indomethacin) or COX-2 inhibitor (NS-398) decreased noradrenaline contraction only in 6- and 12-month-old O-DR, while it remained unmodified by COX-1 inhibitor SC-560. In vessels from 6-month-old O-DR, a similar reduction in the contraction to noradrenaline produced by NS-398 was observed when TP and EP receptors were blocked (SQ29548+AH6809). In 12-month-old O-DR, this effect was only achieved when TP, EP and FP were blocked (SQ29548+AH6809+AL8810). Noradrenaline-stimulated TxB2 and PGE2 release was higher in 6- and 12-month-old O-DR, whereas PGF2α was increased only in 12-month-old O-DR. Our results demonstrated that in utero exposure to maternal hyperglycaemia in rats increases the participation of COX-2-derived prostanoids on contraction to noradrenaline, which might help to explain the greater response to this agonist in MRA from 6- and 12-month-old offspring. As increased contractile response in resistance vessels may contribute to hypertension, our results suggest a role for these COX-2-derived prostanoids in elevating vascular resistance and blood pressure in offspring of diabetic rats. PMID:23209788

Insights from Smart Meters. Ramp-up, dependability, and short-term persistence of savings from Home Energy Reports

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

Todd, Annika; Perry, Michael; Smith, Brian

Smart meters, smart thermostats, and other new technologies provide previously unavailable high-frequency and location-specific energy usage data. Many utilities are now able to capture real-time, customer specific hourly interval usage data for a large proportion of their residential and small commercial customers. These vast, constantly growing streams of rich data (or, “big data”) have the potential to provide novel insights into key policy questions about how people make energy decisions. The richness and granularity of these data enable many types of creative and cutting-edge analytics. Technically sophisticated and rigorous statistical techniques can be used to pull useful insights out ofmore » this high-frequency, human-focused data. In this series, we call this “behavior analytics.” This kind of analytics has the potential to provide tremendous value to a wide range of energy programs. For example, disaggregated and heterogeneous information about actual energy use allows energy efficiency (EE) and/or demand response (DR) program implementers to target specific programs to specific households; enables evaluation, measurement and verification (EM&V) of energy efficiency programs to be performed on a much shorter time horizon than was previously possible; and may provide better insights into the energy and peak hour savings associated with EE and DR programs (e.g., behavior-based (BB) programs). The goal of this series is to enable evidence-based and data-driven decision making by policy makers and industry stakeholders, including program planners, program administrators, utilities, state regulatory agencies, and evaluators. We focus on research findings that are immediately relevant.« less

Effects of dietary restriction on adipose mass and biomarkers of healthy aging in human.

PubMed

Lettieri-Barbato, Daniele; Giovannetti, Esmeralda; Aquilano, Katia

2016-11-29

In developing countries the rise of obesity and obesity-related metabolic disorders, such as cardiovascular diseases and type 2 diabetes, reflects the changes in lifestyle habits and wrong dietary choices. Dietary restriction (DR) regimens have been shown to extend health span and lifespan in many animal models including primates. Identifying biomarkers predictive of clinical benefits of treatment is one of the primary goals of precision medicine. To monitor the clinical outcomes of DR interventions in humans, several biomarkers are commonly adopted. However, a validated link between the behaviors of such biomarkers and DR effects is lacking at present time. Through a systematic analysis of human intervention studies, we evaluated the effect size of DR (i.e. calorie restriction, very low calorie diet, intermittent fasting, alternate day fasting) on health-related biomarkers. We found that DR is effective in reducing total and visceral adipose mass and improving inflammatory cytokines profile and adiponectin/leptin ratio. By analysing the levels of canonical biomarkers of healthy aging, we also validated the changes of insulin, IGF-1 and IGFBP-1,2 to monitor DR effects. Collectively, we developed a useful platform to evaluate the human responses to dietary regimens low in calories.

Dissecting the Gene Network of Dietary Restriction to Identify Evolutionarily Conserved Pathways and New Functional Genes

PubMed Central

Wuttke, Daniel; Connor, Richard; Vora, Chintan; Craig, Thomas; Li, Yang; Wood, Shona; Vasieva, Olga; Shmookler Reis, Robert; Tang, Fusheng; de Magalhães, João Pedro

2012-01-01

Dietary restriction (DR), limiting nutrient intake from diet without causing malnutrition, delays the aging process and extends lifespan in multiple organisms. The conserved life-extending effect of DR suggests the involvement of fundamental mechanisms, although these remain a subject of debate. To help decipher the life-extending mechanisms of DR, we first compiled a list of genes that if genetically altered disrupt or prevent the life-extending effects of DR. We called these DR–essential genes and identified more than 100 in model organisms such as yeast, worms, flies, and mice. In order for other researchers to benefit from this first curated list of genes essential for DR, we established an online database called GenDR (http://genomics.senescence.info/diet/). To dissect the interactions of DR–essential genes and discover the underlying lifespan-extending mechanisms, we then used a variety of network and systems biology approaches to analyze the gene network of DR. We show that DR–essential genes are more conserved at the molecular level and have more molecular interactions than expected by chance. Furthermore, we employed a guilt-by-association method to predict novel DR–essential genes. In budding yeast, we predicted nine genes related to vacuolar functions; we show experimentally that mutations deleting eight of those genes prevent the life-extending effects of DR. Three of these mutants (OPT2, FRE6, and RCR2) had extended lifespan under ad libitum, indicating that the lack of further longevity under DR is not caused by a general compromise of fitness. These results demonstrate how network analyses of DR using GenDR can be used to make phenotypically relevant predictions. Moreover, gene-regulatory circuits reveal that the DR–induced transcriptional signature in yeast involves nutrient-sensing, stress responses and meiotic transcription factors. Finally, comparing the influence of gene expression changes during DR on the interactomes of multiple organisms led us to suggest that DR commonly suppresses translation, while stimulating an ancient reproduction-related process. PMID:22912585

Local and Systemic Inflammatory Biomarkers of Diabetic Retinopathy: An Integrative Approach.

PubMed

Vujosevic, Stela; Simó, Rafael

2017-05-01

To review the usefulness of local and systemic inflammatory biomarkers of diabetic retinopathy (DR) to implement a more personalized treatment. An integrated research (from ophthalmologist and diabetologist point of view) of most significant literature on serum, vitreous, and aqueous humor (AH) biochemical biomarkers related to inflammation at early and advanced stages of DR (including diabetic macular edema [DME] and proliferative DR) was performed. Moreover, novel imaging retinal biomarkers of local "inflammatory condition" were described. Multiple inflammatory cytokines and chemokines are increased in DR in both serum as well as in the eye (vitreous and AH). Nevertheless, local rather than systemic production of proinflammatory cytokines seems more relevant in the pathogenesis of both DR and DME. In the eye, retinal glia cells (macroglia and microglia) together with RPE are major sources of proinflammatory and angiogenic modulators. Retinal imaging allows for noninvasive clinical evaluation of retinal inflammatory response induced by diabetes mellitus. Proinflammatory cytokines/chemokines play an essential role in the pathogenesis of DR. Therefore, circulating biomarkers and retinal imaging aimed at assessing inflammation have emerged as useful tools for monitoring the onset and progression of DR. In addition, "liquid biopsy" of AH seems a good option in patients with advanced stages of DR requiring intravitreous injections. This strategy may permit us to implement a more personalized treatment with better visual function outcome. Further evaluation and validation of circulating and local biomarkers, as well as multimodal imaging is needed to gain new insights into this issue.

Enzyme Amplified Detection of Microbial Cell Wall Components

NASA Technical Reports Server (NTRS)

Wainwright, Norman R.

2004-01-01

This proposal is MBL's portion of NASA's Johnson Space Center's Astrobiology Center led by Principal Investigator, Dr. David McKay, entitled: 'Institute for the Study of Biomarkers in Astromaterials.' Dr. Norman Wainwright is the principal investigator at MBL and is responsible for developing methods to detect trace quantities of microbial cell wall chemicals using the enzyme amplification system of Limulus polyphemus and other related methods.

MicroRNAs to Pathways in Prostate Cancer Progression

DTIC Science & Technology

2015-12-01

PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Dr. Robert Blelloch and Dr. Cassandra Belair email: Robert.Blelloch@ucsf.edu 5e. TASK...Budget period of: 09/30/2013-09/29/2014: Name  Robert Blelloch  Project  Role  PI  Research Identifier Nearest person month  1.2  Contribution to... Project :  Dr. Blelloch was responsible for overall  coordination of this  project .  He was involved in  the design, interpretation and publication of all

Aberrant expression and function of death receptor-3 and death decoy receptor-3 in human cancer.

PubMed

Ge, Zhicheng; Sanders, Andrew J; Ye, Lin; Jiang, Wen G

2011-03-01

Death receptor-3 (DR3) and death decoy receptor-3 (DcR3) are both members of the tumour necrosis factor receptor (TNFR) superfamily. The TNFR superfamily contains eight death domain-containing receptors, including TNFR1 (also called DR1), Fas (also called DR2), DR3, DR4, DR5, DR6, NGFR and EDAR. Upon the binding of these receptors with their corresponding ligands, the death domain recruits various proteins that mediate both the death and proliferation of cells. Receptor function is negatively regulated by decoy receptors (DcR1, DcR2, DcR3 and OPG). DR3/DcR3 are a pair of positive and negative players with which vascular endothelial growth inhibitor (VEGI) interacts. VEGI has been suggested to be a potential tumour suppressor. The inhibitory effects of VEGI on cancer are manifested in three main areas: a direct effect on cancer cells, an anti-angiogenic effect on endothelial cells, and the stimulation of dendritic cell maturation. A recent study indicated that DR3 may be a new receptor for E-selectin, which has been reported to be associated with cancer metastasis. DcR3 is a soluble receptor, highly expressed in various tumours, which lacks an apparent transmembrane segment, prevents cytokine response through ligand binding and neutralization, and is an inhibitor of apoptosis. DcR3 serves as a decoy receptor for FasL, LIGHT and VEGI. The cytokine LIGHT activates various anti-tumour functions and is expected to be a promising candidate for cancer therapy. Certain tumours may escape FasL-dependent immune-cytotoxic attack by expressing DcR3, which blocks FasL function. DR3/DcR3 play profound roles in regulating cell death and proliferation in cancer. The present review briefly discusses DR3/DcR3 and attempts to elucidate the role of these negative and positive players in cancer.

Acquired Resistance Mechanisms to Combination Met-TKI/EGFR-TKI Exposure in Met-Amplified EGFR-TKI-Resistant Lung Adenocarcinoma Harboring an Activating EGFR Mutation.

PubMed

Yamaoka, Toshimitsu; Ohmori, Tohru; Ohba, Motoi; Arata, Satoru; Kishino, Yasunari; Murata, Yasunori; Kusumoto, Sojiro; Ishida, Hiroo; Shirai, Takao; Hirose, Takashi; Ohnishi, Tsukasa; Sasaki, Yasutsuna

2016-12-01

Met-amplified EGFR-tyrosine kinase inhibitor (TKI)-resistant non-small cell lung cancer (NSCLC) harboring an activating EGFR mutation is responsive to concurrent EGFR-TKI and Met-TKI treatment in a preclinical model. Here, we determined that Met-amplified gefitinib-resistant cells acquire dual resistance to inhibition of EGFR and Met tyrosine kinase activities. PC-9 lung adenocarcinoma cells harboring 15-bp deletions (Del E746_A750) in EGFR exon 19 were treated with increasing concentrations of the Met-TKI PHA665752 and 1 μmol/L gefitinib for 1 year; three resistant clones were established via Met amplification. The three dual-resistance cell lines (PC-9DR2, PC-9DR4, and PC-9DR6, designated as DR2, DR4, and DR6, respectively) exhibited different mechanisms for evading both EGFR and Met inhibition. None of the clones harbored a secondary mutation of EGFR T790M or a Met mutation. Insulin-like growth factor (IGF)/IGF1 receptor activation in DR2 and DR4 cells acted as a bypass signaling pathway. Met expression was attenuated to a greater extent in DR2 than in PC-9 cells, but was maintained in DR4 cells by overexpression of IGF-binding protein 3. In DR6 cells, Met was further amplified by association with HSP90, which protected Met from degradation and induced SET and MYND domain-containing 3 (SMYD3)-mediated Met transcription. This is the first report describing the acquisition of dual resistance mechanisms in NSCLC harboring an activating EGFR mutation to Met-TKI and EGFR-TKI following previous EGFR-TKI treatment. These results might inform the development of more effective therapeutic strategies for NSCLC treatment. Mol Cancer Ther; 15(12); 3040-54. ©2016 AACR. ©2016 American Association for Cancer Research.

Peritonitis from perforated peptic ulcer and immune response.

PubMed

Schietroma, Mario; Piccione, Federica; Carlei, Francesco; Sista, Federico; Cecilia, Emanuela Marina; Amicucci, Gianfranco

2013-10-01

Elevated intra-abdominal pressure during the laparoscopy may promote bacteremia, endotoxemia, and systemic inflammatory response. In patients with generalized peritonitis from perforated peptic ulcer (PPU), we sought to compare acute phase response, immunologic status, and bacterial translocation from laparoscopic and open approach. From July 2005 to September 2011, 115 consecutive patients underwent peptic ulcer repair for PPU: 58 cases laparoscopic peptic ulcer repair (LR) and 57 cases open peptic ulcer repair (OR). Bacteremia, endotoxemia, white blood cells population, human leukocyte antigen-DR (HLA-DR), neutrophil-elastase, interleukin-1 and 6 (IL-1 and IL-6), and C-reactive protein (CRP) were investigated. Patients characteristics and grade of peritoneal contamination were similar in the two groups. One hour after intervention, bacteremia was significantly higher in the "open" group than in the laparoscopic group (p < .001). A significantly higher concentration of systemic endotoxin was detected intraoperatively in the "open" group of patients in comparison to the laparoscopic group (p < .0001). Laparotomy caused a significant increase in neutrophil concentration, neutrophil-elastase, IL-1 and IL-6, CRP, and decrease of HLA-DR. We recorded six cases (10.3%) of intra-abdominal abscess in the "open" group and one (1.7%) in laparoscopic group (p < .001). OR, in case of peritonitis after PPU, increased the incidence of bacteremia, endotoxemia, and systemic inflammation compared with LR. Early enhanced postoperative systemic inflammation may cause lower transient immunologic defense after laparotomy (decrease of HLA-DR), leading to enhanced sepsis in these patients.

Technology enablers for improved aerospace x-ray NDE

NASA Astrophysics Data System (ADS)

Strabel, George; Ross, Joseph; Graham, Larry; Smith, Kevin

1996-11-01

In the current climate of reduced Military spending and lower commercial demand for aerospace products, it is of critical importance to allocate scarce technology development resources to meet projected needs. During the past decade, dramatic advances in x-ray nondestructive evaluation (NDE) technology have results in commercially viable digital radiography (DR) and computed tomography (CT) systems. X-ray CT has become an important NDE technique that not only provides data about material integrity, but also valuable volumetric data which is finding applications in reverse engineering, rapid prototyping, process control and 3D metrology. Industrial DR and CT systems have been available for almost 10 years, but are very costly, generally designed for specific applications and have well known limitations for both process development and final inspection. They have inadequate energy/flux to penetrate many large components and structures. In order to support the US Aerospace Industry in its drive towards global competitiveness, it is imperative that key enabling tools such as DR and CT be improved, made affordable, and implemented to meet the anticipated needs of the next decade of aerospace applications. This paper describes a strategy for a consortium of suppliers and users of x-ray NDE systems, academia and national laboratories to work together to attain this goal.

Naringin attenuates diabetic retinopathy by inhibiting inflammation, oxidative stress and NF-κB activation in vivo and in vitro

PubMed Central

Liu, Lihua; Zuo, Zhongfu; Lu, Sijing; Liu, Aihua; Liu, Xuezheng

2017-01-01

Objective(s): Naringin, an essential flavonoid, inhibits inflammatory response and oxidative stress in diabetes. However, whether naringin has beneficial effects on diabetic retinopathy (DR) remains unknown. Materials and Methods: Streptozotocin (STZ, 65 mg/kg) was intraperitoneally injected into male rats (8 weeks old weighting 200-250 g) to establish diabetic model, then naringin (20, 40 or 80 mg/kg/day) was intraperitoneally injected into the diabetic rats for twelve weeks. Glial fibrillary acidic protein (GFAP) level, thickness of ganglion cell layer (GCL) and ganglion cell counts were assessed in diabetic retina in vivo. Naringin (50 μM) that significantly inhibited high glucose (HG, 25 mM)-induced cell proliferation was used to treat rat Muller cell line (rMC1) in vitro. Inflammatory response, oxidative stress and activation of nuclear factor kappa B (NF-κB) p65 were evaluated in retina in vivo and in rMC1 cells in vitro. Results: Naringin alleviated DR symptoms as evidenced by the increased retinal ganglion cells and decreased GFAP level in rat retina. Naringin exhibited anti-inflammatory and antioxidative effects as confirmed by the down-regulated pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and the up-regulated antioxidants, glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in DR rats. Moreover, we found that naringin inhibited HG-induced proliferation, abnormal inflammatory response and oxidative stress in rMC1 cells. In addition, the enhanced nuclear translocation of NF-κB p65 in diabetic rat retina and HG-induced rMC1 cells was suppressed by naringin. Conclusion: Naringin attenuates inflammatory response, oxidative stress and NF-κB activation in experimental models of DR. PMID:28852447

Naringin attenuates diabetic retinopathy by inhibiting inflammation, oxidative stress and NF-κB activation in vivo and in vitro.

PubMed

Liu, Lihua; Zuo, Zhongfu; Lu, Sijing; Liu, Aihua; Liu, Xuezheng

2017-07-01

Naringin, an essential flavonoid, inhibits inflammatory response and oxidative stress in diabetes. However, whether naringin has beneficial effects on diabetic retinopathy (DR) remains unknown. Streptozotocin (STZ, 65 mg/kg) was intraperitoneally injected into male rats (8 weeks old weighting 200-250 g) to establish diabetic model, then naringin (20, 40 or 80 mg/kg/day) was intraperitoneally injected into the diabetic rats for twelve weeks. Glial fibrillary acidic protein (GFAP) level, thickness of ganglion cell layer (GCL) and ganglion cell counts were assessed in diabetic retina in vivo . Naringin (50 μM) that significantly inhibited high glucose (HG, 25 mM)-induced cell proliferation was used to treat rat Muller cell line (rMC1) in vitro . Inflammatory response, oxidative stress and activation of nuclear factor kappa B (NF-κB) p65 were evaluated in retina in vivo and in rMC1 cells in vitro . Naringin alleviated DR symptoms as evidenced by the increased retinal ganglion cells and decreased GFAP level in rat retina. Naringin exhibited anti-inflammatory and antioxidative effects as confirmed by the down-regulated pro-inflammatory cytokines, tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6), and the up-regulated antioxidants, glutathione (GSH), superoxide dismutase (SOD) and catalase (CAT) in DR rats. Moreover, we found that naringin inhibited HG-induced proliferation, abnormal inflammatory response and oxidative stress in rMC1 cells. In addition, the enhanced nuclear translocation of NF-κB p65 in diabetic rat retina and HG-induced rMC1 cells was suppressed by naringin. Naringin attenuates inflammatory response, oxidative stress and NF-κB activation in experimental models of DR.

Roles of the eye care workforce for task sharing in management of diabetic retinopathy in Cambodia

PubMed Central

Shah, Mufarriq; Ormsby, Gail M.; Noor, Ayesha; Chakrabarti, Rahul; Mörchen, Manfred; Islam, Fakir M Amirul; Harper, C Alex; Keeffe, Jill E

2018-01-01

AIM To identify the current roles of eye and health care workers in eye care delivery and investigate their potential roles in screening and detection for management of diabetic retinopathy (DR) through task sharing. METHODS Purposive sampling of 24 participants including health administrators, members from non-government organizations and all available eye care workers in Takeo province were recruited. This cross sectional mixed method study comprised a survey and in-depth interviews. Data were collected from medical records at Caritas Takeo Eye Hospital (CTEH) and Kiri Vong District Referral Hospital Vision Centre, and a survey and interviews with participants were done to explore the potential roles for task sharing in DR management. Qualitative data were transcribed into a text program and then entered into N-Vivo (version 10) software for data management and analysis. RESULTS From 2009 to 2012, a total of 105 178 patients were examined and 14 030 eye surgeries were performed in CTEH by three ophthalmologists supported by ophthalmic nurses in operating and eye examination for patients. Between January 2011 and September 2012, 151 patients (72 males) with retinal pathology including 125 (83%) with DR visited CTEH. In addition 170 patients with diabetes were referred to CTEH for eye examinations from Mo Po Tsyo screening programs for people with diabetes. Factors favouring task sharing included high demand for eye care services and scarcity of ophthalmologists. CONCLUSION Task sharing and team work for eye care services is functional. Participants favor the potential role of ophthalmic nurses in screening for DR through task sharing. PMID:29375999

On Contemporary War and the German Armed Forcs: The Afghan War and and Its Consequenes

DTIC Science & Technology

2014-06-01

Minister of Defense Volker Rühe, and in 2008 amended during the term of office of Minister of Defense Dr. Jung, it 38 Wolfgang Schneiderhahn, “Das Bild... Krause (Opladen: Verlag Barbara Budrich, 2006), 233. 134 Reiner Pommerin, “Vom ‘Kalten Krieg’ zu globaler Konfliktverhütung und Krisenbewältigung...Jahrhundert [Bundeswehr: The Next 50 Years, Demands on German Forces in the 21st Century], edited by Jan C. Irlenkaeuser, Joachim Krause . Opladen

Elusive Agreement: The Sporazum of 1939 and the Serb-croat Dispute in the Context of European Crisis

DTIC Science & Technology

1992-05-01

opportunities to verbalize and refine my ideas. I especially wish to thank Dr. Matt Taylor, A. J. Hood, Jeff Hooton, and Tom Little for their help and...Belgrade, provoked by the violence in Croatia, demanded "a war of extermination between the two South Slav peoples." (See Jelavich and Jelavich...June 1928, the legislative sessions had degenerated into scenes of riotous disorder, taunts, and fisticuffs. The violence reached a fatal crescendo on

Transgastric Local Pancreatic Hypothermia: A Novel, Rapid Multimodal Therapy for Acute Pancreatitis

DTIC Science & Technology

2016-02-01

PRINCIPAL INVESTIGATOR: Dr. Vijay P. Singh CONTRACTING ORGANIZATION: Mayo Clinic Arizona Scottsdale, AZ 85259. REPORT DATE : Feb 2016 TYPE OF REPORT...PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1. REPORT DATE Feb 2016 2. REPORT TYPE Annual Report 3. DATES COVERED 8Jan2015 - 7Jan2016 4...increased metabolic demand during severe (GTL) but not mild AP. Thus this concept/technology/ method may be used to make an early distinction between mild

Oroxylin A reverses CAM-DR of HepG2 cells by suppressing Integrinβ1 and its related pathway

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

Zhu, Binbin; Zhao, Li; Zhu, Litao

Oroxylin A, a naturally occurring monoflavonoid extracted from Scutellariae radix, shows effective anticancer activities and low toxicities both in vivo and in vitro in previous studies. In this study, we investigated whether the CAM-DR model of HepG2 cells showed resistance to cytotoxic agents compared with normally cultured HepG2 cells. Furthermore, after the treatment of Paclitaxel, less inhibitory effects and decreased apoptosis rate were detected in the model. Data also revealed increased expression of Integrinβ1 might be responsible for the resistance ability. Moreover, Integrinβ1-siRNA-transfected CAM-DR HepG2 cells exhibited more inhibitory effects and higher levels of apoptosis than the non-transfected CAM-DR cells.more » The data corroborated that Integrinβ1 played a significant role in CAM-DR. After the treatment of weakly-toxic concentrations of Oroxylin A, the apoptosis induced by Paclitaxel in the CAM-DR model increased dramatically. Western blot assay revealed Oroxylin A markedly down-regulated the expression of Integrinβ1 and the activity of related pathway. As a conclusion, Oroxylin A can reverse the resistance of CAM-DR via inhibition of Integrinβ1 and its related pathway. Oroxylin A may be a potential candidate of a CAM-DR reversal agent. Highlights: ► Adhesion of HepG2 cells to fibronectin exhibited resistance to Paclitaxel. ► The resistance was associated with the increased expression of Integrinβ1. ► Knocking down Integrinβ1 can increase the toxicity of Paclitaxel on CAM-DR model. ► Oroxylin A reversed the resistance by suppressing Integrinβ1 and related pathway.« less

Chronic Ca2+ influx through voltage-dependent Ca2+ channels enhance delayed rectifier K+ currents via activating Src family tyrosine kinase in rat hippocampal neurons.

PubMed

Yang, Yoon-Sil; Jeon, Sang-Chan; Kim, Dong-Kwan; Eun, Su-Yong; Jung, Sung-Cherl

2017-03-01

Excessive influx and the subsequent rapid cytosolic elevation of Ca 2+ in neurons is the major cause to induce hyperexcitability and irreversible cell damage although it is an essential ion for cellular signalings. Therefore, most neurons exhibit several cellular mechanisms to homeostatically regulate cytosolic Ca 2+ level in normal as well as pathological conditions. Delayed rectifier K + channels (I DR channels) play a role to suppress membrane excitability by inducing K + outflow in various conditions, indicating their potential role in preventing pathogenic conditions and cell damage under Ca 2+ -mediated excitotoxic conditions. In the present study, we electrophysiologically evaluated the response of I DR channels to hyperexcitable conditions induced by high Ca 2+ pretreatment (3.6 mM, for 24 hours) in cultured hippocampal neurons. In results, high Ca 2+ -treatment significantly increased the amplitude of I DR without changes of gating kinetics. Nimodipine but not APV blocked Ca 2+ -induced I DR enhancement, confirming that the change of I DR might be targeted by Ca 2+ influx through voltage-dependent Ca 2+ channels (VDCCs) rather than NMDA receptors (NMDARs). The VDCC-mediated I DR enhancement was not affected by either Ca 2+ -induced Ca 2+ release (CICR) or small conductance Ca 2+ -activated K + channels (SK channels). Furthermore, PP2 but not H89 completely abolished I DR enhancement under high Ca 2+ condition, indicating that the activation of Src family tyrosine kinases (SFKs) is required for Ca 2+ -mediated I DR enhancement. Thus, SFKs may be sensitive to excessive Ca 2+ influx through VDCCs and enhance I DR to activate a neuroprotective mechanism against Ca 2+ -mediated hyperexcitability in neurons.

Plasticity of vagal brainstem circuits in the control of gastrointestinal function

PubMed Central

Browning, Kirsteen N; Travagli, R. Alberto

2010-01-01

The afferent vagus transmits sensory information from the gastrointestinal (GI) tract and other viscera to the brainstem via a glutamatergic synapse at the level of the nucleus of the solitary tract (NTS). Second order NTS neurons integrate this sensory information with inputs from other CNS regions that regulate autonomic functions and homeostasis. Glutamatergic and GABAergic neurons are responsible for conveying the integrated response to other nuclei, including the adjacent dorsal motor nucleus of the vagus (DMV). The preganglionic neurons in the DMV are the source of the parasympathetic motor response back to the GI tract. The glutamatergic synapse between the NTS and DMV is unlikely to be tonically active in regulating gastric motility and tone although almost all neurotransmitters tested so far modulate transmission at this synapse. In contrast, the tonic inhibitory GABAergic input from the NTS to the DMV appears to be critical in setting the tone of gastric motility and, under basal conditions, is unaffected by many neurotransmitters or neurohormones. This review is based, in part, on a presentation by Dr Browning at the 2009 ISAN meeting in Sydney, Australia and discusses how neurohormones and macronutrients modulate glutamatergic transmission to NTS neurons and GABAergic transmission to DMV neurons in relation to sensory information that is received from the GI tract. These neurohormones and macronutrients appear to exert efficient “on-demand” control of the motor output from the DMV in response to ever-changing demands required to maintain homeostasis. PMID:21147043

Radio Frequency Controlled Stimulation of Intracellular Gold or Silver Nanoparticle Conjugates for Use as Potential Sensors or Modulators of Biological Function

DTIC Science & Technology

2010-09-01

SIGNED//___________ DAVID R. MATTIE , PhD, DR-III...RESPONSIBLE PERSON David R. Mattie a. REPORT U b. ABSTRACT U c. THIS PAGE U SAR 72 19b. TELEPHONE...used as a cellular model to determine the interaction of NPs with human skin. HaCaT cells were donated generously by Dr. James F. Dillman III, of the

Reply to comment by Rannik on "A simple method for estimating frequency response corrections for eddy covariance systems"

Treesearch

W. J. Massman

2001-01-01

First, my thanks to Dr. Ullar Rannik for his interest and insights in my recent study of spectral corrections and associated eddy covariance flux loss (Massman, 2000, henceforth denoted by M2000). His comments are important and germane to the attenuation of low frequencies of the turbulent cospectra due to recursive filtering and block averaging. Dr. Rannik addresses...

Thermospheric Neutral Wind Measurement Using the LWA1 and the AFRL Digisonde

DTIC Science & Technology

2014-09-26

Dr. Stephen White Project Manager, AFRL/RVBXS Chief, Battlespace Environment Division This report is published in the...CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON Dr. Stephen White a. REPORT Unclassified b...emission from meteors has not been previously detected, but this is not the first time its existence has been discussed. Hawkins (1958) conducted a

USAF/SCEEE Summer Faculty Research Program (1982). Management Report.

DTIC Science & Technology

1982-10-01

Patrick J. Sweeney, Ph.D., P.E. Mary Doddy, M.S. ABSTRACT This dynamic simulation computer model demonstrates the affects of C-forces upon the eyeball...Assistant Professor Specialty: Numerical Modeling and University of Lowell Computer Simulation of Mathematics Department Geophysical Problems Lowell...Problems And Promises 25 Modeling And Tracking Saccadic Dr. John D. Enderle Eye Movements 26 Dynamic Response Of Doubly Curved Dr. Fernando E. Fagundo

High Power Magnetohydrodynamic System

DTIC Science & Technology

1978-07-01

AFAPL/POD as the Program Manager. Dr. Daniel W. Swallom and Dr. Otto K. Sonju of Maxwell Laboratories, Inc. were responsible for the technical work. The...fabricated and tested. Figure 1 shows this hardware installed at the Santa Susana Field Laboratory (SSFL) for develop- ment testing. The cooled wall...development test program was conducted at Santa Susana Field Laboratory (SSFL) and a performance test program is to be conducted at AEDC. AEDC is to

STEADY-STATE SOLUTIONS TO PBPK MODELS AND THEIR APPLICATIONS TO RISK ASSESSMENT I: ROUTE-TO-ROUTE EXTRAPOLATION OF VOLATILE CHEMICALS - AUTHORS' RESPONSE TO LETTER BY DR. KENNETH BOGEN

EPA Science Inventory

Dear Editor: We are disappointed that Dr. Bogen felt our paper(1) “adds little new” to previously published work utilizing steady state solutions to PBPK models. Moreover, it was not our intention to be either “dismissive” or “misleading” in our admittedly brief citation of the...

[Story of three SS dentists during World War II: Pr Hugo Blaschke, Dr Hermann Pook and Dr Willy Frank].

PubMed

Riaud, Xavier

2006-12-01

This story of three SS dentists shows very clearly that the medical code of ethics, under a totalitarian regime, ends where ideology begins. Professor Hugo Blaschke provided dental care to the most eminent Nazi leaders, but he also was the senior SS dentist. He was in charge of dental care in the Waffen-SS, and therefore, he had responsibility for the stocks of dental gold collected from the mouths of those who died in the concentration camps, in order to make dentures for his soldiers. Dr Hermann Pook was the dentist in charge of all the other dentists practising in the concentration camps. He was responsible for gathering statistics on the dental care provided for prisoners in the camps. His instructions were very clear: "No conservation or restorative treatment. Only extractions, and with no anaesthesia!" He was also in charge of gathering the gold that was collected in the camps, for the financial department of the SS. Dr Willy Frank, an Auschwitz dentist, took part in the selection of some of the convoys for the gas chambers. His participation in the collection of gold from the mouths of the dead was also established. These three men were sentenced to prison for War Crimes and Crimes against Humanity.

Emergence of dendritic cells in the myocardium after acute myocardial infarction - implications for inflammatory myocardial damage.

PubMed

Yilmaz, Atilla; Dietel, Barbara; Cicha, Iwona; Schubert, Katja; Hausmann, Roland; Daniel, Werner G; Garlichs, Christoph D; Stumpf, Christian

2010-03-01

Dendritic cells (DC) are crucial for T cell mediated immune responses. Recently, we observed a significant decrease in circulating myeloid DC precursors in patients with acute myocardial infarction (AMI). The aim of the present study was to investigate whether myeloid DC are present in infarcted myocardium. Myocardial specimens of 10 patients with AMI and 7 accident victims (controls) were collected after autopsy. In immunostainings the presence of DC (CD209(+), fascin(+)), T cells (CD3(+)), macrophages (CD68(+)), and HLA-DR expression was analyzed. Significantly higher numbers of CD209(+)-DC (97 vs. 44 cells/0.25 mm(2), p=0.03), fascin(+)-DC (54 vs. 8 cells/0.25 mm(2), p=0.02), T cells (27 vs. 6 cells/0.25 mm(2), p=0.02), and macrophages (44 vs. 6 cells/0.25 mm(2), p=0.01) associated with high HLA-DR expression were detected in infarcted myocardium. Frequent colocalizations of DC and T cells were observed. In occluded coronary arteries numerous DC, T cells, macrophages and high HLA-DR expression were found. We show that DC are present in infarcted myocardium after AMI. High HLA-DR expression and the colocalization with T cells suggest that they might trigger an immune response leading to further myocardial damage.

Stress modulation of cognitive and affective processes

PubMed Central

CAMPEAU, SERGE; LIBERZON, ISRAEL; MORILAK, DAVID; RESSLER, KERRY

2012-01-01

This review summarizes the major discussion points of a symposium on stress modulation of cognitive and affective processes, which was held during the 2010 workshop on the neurobiology of stress (Boulder, CO, USA). The four discussants addressed a number of specific cognitive and affective factors that are modulated by exposure to acute or repeated stress. Dr David Morilak discussed the effects of various repeated stress situations on cognitive flexibility, as assessed with a rodent model of attentional set-shifting task, and how performance on slightly different aspects of this test is modulated by different prefrontal regions through monoaminergic neurotransmission. Dr Serge Campeau summarized the findings of several studies exploring a number of factors and brain regions that regulate habituation of various autonomic and neuroendocrine responses to repeated audiogenic stress exposures. Dr Kerry Ressler discussed a body of work exploring the modulation and extinction of fear memories in rodents and humans, especially focusing on the role of key neurotransmitter systems including excitatory amino acids and brain-derived neurotrophic factor. Dr Israel Liberzon presented recent results on human decision-making processes in response to exogenous glucocorticoid hormone administration. Overall, these discussions are casting a wider framework on the cognitive/affective processes that are distinctly regulated by the experience of stress and some of the brain regions and neurotransmitter systems associated with these effects. PMID:21790481

Dynamics Determine Signaling in a Multicomponent System Associated with Rheumatoid Arthritis.

PubMed

Lindgren, Cecilia; Tyagi, Mohit; Viljanen, Johan; Toms, Johannes; Ge, Changrong; Zhang, Naru; Holmdahl, Rikard; Kihlberg, Jan; Linusson, Anna

2018-05-24

Strategies that target multiple components are usually required for treatment of diseases originating from complex biological systems. The multicomponent system consisting of the DR4 major histocompatibility complex type II molecule, the glycopeptide CII259-273 from type II collagen, and a T-cell receptor is associated with development of rheumatoid arthritis (RA). We introduced non-native amino acids and amide bond isosteres into CII259-273 and investigated the effect on binding to DR4 and the subsequent T-cell response. Molecular dynamics simulations revealed that complexes between DR4 and derivatives of CII259-273 were highly dynamic. Signaling in the overall multicomponent system was found to depend on formation of an appropriate number of dynamic intramolecular hydrogen bonds between DR4 and CII259-273, together with the positioning of the galactose moiety of CII259-273 in the DR4 binding groove. Interestingly, the system tolerated modifications at several positions in CII259-273, indicating opportunities to use analogues to increase our understanding of how rheumatoid arthritis develops and for evaluation as vaccines to treat RA.

Design of demand side response model in energy internet demonstration park

NASA Astrophysics Data System (ADS)

Zhang, Q.; Liu, D. N.

2017-08-01

The implementation of demand side response can bring a lot of benefits to the power system, users and society, but there are still many problems in the actual operation. Firstly, this paper analyses the current situation and problems of demand side response. On this basis, this paper analyses the advantages of implementing demand side response in the energy Internet demonstration park. Finally, the paper designs three kinds of feasible demand side response modes in the energy Internet demonstration park.

Protecting paradise: tourism and AIDS in the Dominican Republic.

PubMed

Forsythe, S; Hasbún, J; Butler de Lister, M

1998-09-01

This study summarizes results from six data collection instruments administered to tourists, hotel workers, and commercial sex workers (CSWs) in the Dominican Republic (D.R.). The objective of this study was to assess: 1. how HIV/AIDS may affect tourism; 2. how tourists are likely to react to prevention campaigns; and 3. how tourism may affect the spread of HIV/AIDS. It was found that an overwhelming proportion of tourists did not consider the prevalence of HIV to be a factor when making their travel plans, and that most did not consider themselves at greater risk of becoming infected while on holiday than when they were at home. This study determined that the spread of HIV/AIDS was unlikely to affect the demand for tourism services in the D.R. The study also found that most tourists would respond positively to an HIV/AIDS prevention campaign and would not be discouraged from visiting the D.R. because of such campaigns. Those most receptive to prevention efforts were also those who felt they were at highest risk, according to study data. Finally, it was determined that while most tourists probably do not engage in high risk activities, there were some male and female tourists who do engage in sexual encounters with multiple Dominican CSWs and hotel employees. These encounters represent a risk to the health and economic development of the D.R., as well as to tourists and their other sexual partners. Based on these findings, it is recommended that in order to minimize the potential social and economic impact of HIV/AIDS in the D.R., prevention messages need to reach a number of groups which have not yet been adequately targeted. These groups include tourists, with a special emphasis on 'sex tourists', and hotel employees, with a special emphasis on entertainment staff.

Robust Unit Commitment Considering Uncertain Demand Response

DOE PAGES

Liu, Guodong; Tomsovic, Kevin

2014-09-28

Although price responsive demand response has been widely accepted as playing an important role in the reliable and economic operation of power system, the real response from demand side can be highly uncertain due to limited understanding of consumers' response to pricing signals. To model the behavior of consumers, the price elasticity of demand has been explored and utilized in both research and real practice. However, the price elasticity of demand is not precisely known and may vary greatly with operating conditions and types of customers. To accommodate the uncertainty of demand response, alternative unit commitment methods robust to themore » uncertainty of the demand response require investigation. In this paper, a robust unit commitment model to minimize the generalized social cost is proposed for the optimal unit commitment decision taking into account uncertainty of the price elasticity of demand. By optimizing the worst case under proper robust level, the unit commitment solution of the proposed model is robust against all possible realizations of the modeled uncertain demand response. Numerical simulations on the IEEE Reliability Test System show the e ectiveness of the method. Finally, compared to unit commitment with deterministic price elasticity of demand, the proposed robust model can reduce the average Locational Marginal Prices (LMPs) as well as the price volatility.« less

Effect of Eucommia ulmoides Oliv., Gynostemma pentaphyllum (Thunb.) Makino, and Curcuma longa L. on Th1- and Th2-cytokine responses and human leukocyte antigen-DR expression in peripheral blood mononuclear cells of septic patients.

PubMed

Wu, Huang-Pin; Lin, Yin-Ku

2018-05-10

Many traditional Chinese medicines (TCM), such as Eucommia ulmoides Oliv., Gynostemma pentaphyllum (Thunb.) Makino, and Curcuma longa L., have been reported to have various immune-modulatory effects. To determine the effects of extracts from these three TCM on type 1 T help (Th1)- and Th2-cytokine responses and human leukocyte antigen (HLA)-DR expression in peripheral blood mononuclear cells (PBMCs) obtained from septic patients. Lipopolysaccharide (LPS)-stimulated PBMCs of healthy controls and septic patients were cultured for 48 hs with or without 0.05/0.1 mg/ml of TCM extract. HLA-DR expression in monocytes was detected using flow cytofluorimetry. The interferon [IFN]-γ, tumor necrosis factor [TNF]-α, interleukin (IL)- 2, IL-5, IL-10, and IL-13 levels in supernatants were measured with a human enzyme-linked immunosorbent assay. Treatment with either 0.05 or 0.1 mg/ml of C. longa L. extract significantly restored the percentage of HLA-DR-positive monocytes, which was decreased by LPS in control and patient groups. Treatment with 0.05 or 0.1 mg/ml E. ulmoides Oliv. and C.longa L. extract decreased IL-10 production from LPS-stimulated PBMCs of controls and patients. In patients with sepsis, C. longa L. extract decreased IL-10 production to a greater degree than did E. ulmoides Oliv extract. Although IFN-γ, TNF-α, or IL-13 productions from LPS-stimulated PBMCs were influenced by E. ulmoides Oliv., G. pentaphyllum (Thunb.) Makino, or C. longa L. in control or sepsis groups in this study, only the influence of IL-10 was consistent in both control and sepsis groups. By enhancing monocyte HLA-DR expression and decreasing IL-10 production, C. longa L. might help restore inflammatory responses in septic patients to eradicate pathogens. Copyright © 2018 Elsevier B.V. All rights reserved.

Emerging Trends of HIV Drug Resistance in Chinese HIV-Infected Patients Receiving First-Line Highly Active Antiretroviral Therapy: A Systematic Review and Meta-Analysis

PubMed Central

Liu, Huixin; Ma, Ye; Su, Yingying; Smith, M. Kumi; Liu, Ying; Jin, Yantao; Gu, Hongqiu; Wu, Jing; Zhu, Lin; Wang, Ning

2014-01-01

Background. Highly active antiretroviral therapy (HAART) has led to a dramatic decrease in AIDS-related morbidity and mortality through sustained suppression of human immunodeficiency virus (HIV) replication and reconstitution of the immune response. Settings like China that experienced rapid HAART rollout and relatively limited drug selection face considerable challenges in controlling HIV drug resistance (DR). Methods. We conducted a systematic review and meta-analysis to describe trends in emergent HIV DR to first-line HAART among Chinese HIV-infected patients, as reflected in the point prevalence of HIV DR at key points and fixed intervals after treatment initiation, using data from cohort studies and cross-sectional studies respectively. Results. Pooled prevalence of HIV DR from longitudinal cohorts studies was 10.79% (95% confidence interval [CI], 5.85%–19.07%) after 12 months of HAART and 80.58% (95% CI, 76.6%–84.02%) after 72 months of HAART. The HIV DR prevalence from cross-sectional studies was measured in treatment intervals; during the 0–12-month HAART treatment interval, the pooled prevalence of HIV DR was 11.1% (95% CI, 7.49%–16.14%), which increased to 22.92% at 61–72 months (95% CI, 9.45%–45.86%). Stratified analyses showed that patients receiving a didanosine-based regimen had higher HIV DR prevalence than those not taking didanosine (15.82% vs 4.97%). Patients infected through former plasma donation and those receiving AIDS treatment at village clinics had higher HIV DR prevalence than those infected through sexual transmission or treated at a county-level hospital. Conclusions. Our findings indicate higher prevalence of HIV DR for patients with longer cumulative HAART exposure, highlighting important subgroups for future HIV DR surveillance and control. PMID:25053721

Losartan reverses COX-2-dependent vascular dysfunction in offspring of hyperglycaemic rats.

PubMed

de Queiroz, Diego Barbosa; Ramos-Alves, Fernanda Elizabethe; Santos-Rocha, Juliana; Duarte, Gloria Pinto; Xavier, Fabiano Elias

2017-09-01

This study examined whether chronic treatment with losartan, an angiotensin II type 1 receptor (AT 1 R) antagonist, might reverse COX-2-mediated vascular dysfunction in mesenteric resistance arteries (MRA) from offspring of hyperglycaemic rats. Male 12-month-old offspring of hyperglycaemic (O-DR) and normoglycaemic (O-CR) rats were treated with losartan (15mg·kg·day -1 ) during 2months. Third order MRA of untreated and losartan-treated O-DR and O-CR were mounted in wire myograph for isometric tension measurements. COX-2 expression was analyzed by Western blot; TxA 2 , PGE 2 and PGF 2α release was measured using commercial kits. O-DR showed increased blood pressure, impaired acetylcholine-induced vasodilation and increased noradrenaline-induced vasoconstriction than O-CR. All these parameters were normalized by losartan in O-DR. Pre-incubation of MRA with indomethacin (COX-1/2 inhibitor), NS-398 (COX-2 inhibitor) or tempol (superoxide dismutase mimetic) increased relaxation to acetylcholine and reduced contraction to noradrenaline only in O-DR. COX-2 expression, TxA 2 , PGE 2 and PGF 2α release were increased in O-DR. In losartan-treated O-DR, NS-398, indomethacin or tempol failed to produce any effect on acetylcholine or noradrenaline responses. Losartan treatment reduced COX-2 expression, TxA 2 , PGE 2 and PGF 2α release in O-DR. The present results reveal that chronic losartan administration in O-DR normalizes endothelial function in MRA by correcting the existing COX-2 overexpression and the imbalance between endothelium-derived relaxing and contracting factors. These findings not only support the beneficial effects of AT 1 receptor antagonist in O-DR, but also suggest the implication of angiotensin II as a putative mediator of hyperglycemia-programmed vascular dysfunction in rats. Copyright © 2017 Elsevier Inc. All rights reserved.

Alpha-1-antitrypsin ameliorates inflammation and neurodegeneration in the diabetic mouse retina.

PubMed

Ortiz, Gustavo; Lopez, Emiliano S; Salica, Juan P; Potilinski, Constanza; Fernández Acquier, Mariano; Chuluyan, Eduardo; Gallo, Juan E

2018-05-18

Diabetic retinopathy (DR) is the most common cause of blindness in the working age population. Early events of DR are accompanied by neurodegeneration of the inner retina resulting in ganglion cell loss. These findings together with reduced retinal thickness are observed within the first weeks of experimental DR. Besides, an inflammatory process is triggered in DR in which the innate immune response plays a relevant role. Alpha 1 antitrypsin (AAT), an inhibitor of serine proteases, has shown anti-inflammatory properties in several diseases. We aimed at evaluating the use of AAT to prevent the early changes induced by DR. Diabetic AAT-treated mice showed a delay on ganglion cell loss and retinal thinning. These animals showed a markedly reduced inflammatory status. AAT was able to preserve systemic and retinal TNF-α level similar to that of control mice. Furthermore, retinal macrophages found in the AAT-treated diabetic mouse exhibited M2 profile (F4/80 + CD206 + ) together with an anti-inflammatory microenvironment. We thus demonstrated that AAT-treated mice show less retinal neurodegenerative changes and have reduced levels of systemic and retinal TNF-α. Our results contribute to shed light on the use of AAT as a possible therapeutic option in DR. Copyright © 2018 Elsevier Ltd. All rights reserved.

Performance evaluation of the active-flow personal DataRAM PM 2.5 mass monitor (Thermo Anderson pDR-1200) designed for continuous personal exposure measurements

NASA Astrophysics Data System (ADS)

Chakrabarti, Bhabesh; Fine, Philip M.; Delfino, Ralph; Sioutas, Constantinos

The need for continuous personal monitoring for exposure to particulate matter has been demonstrated by recent health studies showing effects of PM exposure on time scales of less than a few hours. Filter-based methods cannot measure this short-term variation of PM levels, which can be quite significant considering human activity patterns. The goal of this study was to evaluate the active-flow personal DataRAM for PM 2.5 (MIE pDR-1200; Thermo Electron Corp., Franklin, MA) designed as a wearable monitor to continuously measure particle exposure. The instrument precision was found to be good (2.1%) and significantly higher than the passive pDR configuration tested previously. A comparison to other proven continuous monitors resulted in good agreement at low relative humidities. Results at higher humidity followed predictable trends and provided a correction scheme that improved the accuracy of pDR readings. The pDR response to particle size also corresponded to previously observed and theoretical errors. The active flow feature of the pDR allows collection of the sampled particles on a back-up filter. The 24-h mass measured on this filter was found to compare very well with a Federal Reference Method for PM 2.5 mass.

Synergistic interaction between baclofen administration into the median raphe nucleus and inconsequential visual stimuli on investigatory behavior of rats

PubMed Central

Vollrath-Smith, Fiori R.; Shin, Rick

2011-01-01

Rationale Noncontingent administration of amphetamine into the ventral striatum or systemic nicotine increases responses rewarded by inconsequential visual stimuli. When these drugs are contingently administered, rats learn to self-administer them. We recently found that rats self-administer the GABAB receptor agonist baclofen into the median (MR) or dorsal (DR) raphe nuclei. Objectives We examined whether noncontingent administration of baclofen into the MR or DR increases rats’ investigatory behavior rewarded by a flash of light. Results Contingent presentations of a flash of light slightly increased lever presses. Whereas noncontingent administration of baclofen into the MR or DR did not reliably increase lever presses in the absence of visual stimulus reward, the same manipulation markedly increased lever presses rewarded by the visual stimulus. Heightened locomotor activity induced by intraperitoneal injections of amphetamine (3 mg/kg) failed to concur with increased lever pressing for the visual stimulus. These results indicate that the observed enhancement of visual stimulus seeking is distinct from an enhancement of general locomotor activity. Visual stimulus seeking decreased when baclofen was co-administered with the GABAB receptor antagonist, SCH 50911, confirming the involvement of local GABAB receptors. Seeking for visual stimulus also abated when baclofen administration was preceded by intraperitoneal injections of the dopamine antagonist, SCH 23390 (0.025 mg/kg), suggesting enhanced visual stimulus seeking depends on intact dopamine signals. Conclusions Baclofen administration into the MR or DR increased investigatory behavior induced by visual stimuli. Stimulation of GABAB receptors in the MR and DR appears to disinhibit the motivational process involving stimulus–approach responses. PMID:21904820

Dual role of DR5 in death and survival signaling leads to TRAIL resistance in cancer cells

PubMed Central

Shlyakhtina, Yelyzaveta; Pavet, Valeria; Gronemeyer, Hinrich

2017-01-01

Besides its tumor-selective apoptotic activity, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) promotes pro-survival, proliferative or migratory signaling (NF-κB, PI3K/Akt, MAPK and JNK; referred to as 'non-apoptotic' cascades). Indeed, apoptosis and non-apoptotic signaling can be activated in clonal populations of cancer cells in response to treatment and, as a result, only a part of the initial cellular population dies while a fraction survives and develops resistance to TRAIL-induced apoptosis (referred to as 'fractional survival'). Notably, the molecular characterization of the protein platforms streaming into tumoricidal versus tumor-promoting cascades that control fractional survival remained elusive. Here we demonstrate that, in the context of DR4–DR5–DcR2 hetero-oligomeric complexes, a single death receptor (DR5) suffices to assemble composite plasma membrane-proximal pro-apoptotic/pro-survival platforms that propagate TRAIL signaling to both death and survival pathways in clonal populations of cancer cells. Moreover, we show that while all members of TRAIL-induced complexes support survival, none of them acted exclusively pro-apoptotic. Indeed, key apoptotic proteins as FADD and procaspase-8 were also involved in transducing non-apoptotic signaling in response to this cytokine. Collectively, this study reveals the Janus faces of DR5, and the contributions of other death complex components in fractional survival that foster the generation of resistance. Our data highlight a new level of complexity in TRAIL signaling and point to an improved therapeutic rationale in view of hitherto disappointing results. PMID:29048428

Commentary: taking a deep breath before reflecting on differential response.

PubMed

Merkel-Holguin, Lisa; Bross, Donald C

2015-01-01

Although there are certainly limitations to each and every research and evaluation project in child welfare, as with other fields of study, understanding DR as a CPS reform has been fostered through many thoughtful and rigorous studies that have employed random control trial evaluation designs. For each assumption addressed in this commentary, we have raised a few questions. For all interested in CPS reform, other questions arise because child protection and child welfare professionals are trying to encourage more scientific ways of thinking as a means of engendering improvements: 1. Has the research on DR spotlighted the inadequacy of CPS interventions, either AR or IR? A high percentage of CPS responses are short-term. Is it reasonable to expect significant differences between AR and IR families and improvements in the CPS population, given that families often present with problems characterized as intractable but the intensity of the CPS response, coupled with limited service availability and accessibility, may not be sufficient to meet family needs? 2. Has the DR research, which has mainly focused on AR families, also highlighted the glaring absence of quality research in what is effective in producing positive outcomes for families that receive traditional child abuse and neglect investigations? 3. Does the implementation of DR move the CPS field ahead in terms of making better triage decisions, identifying especially those that require CPS involvement as compared to those who will benefit from but might not absolutely need intervention? Is 'triage' an explicit assumption of the DR innovation? Is it an implicit assumption of DR, however defined? If triage is not part of the research, does the ability of child protection to respond both differentially and also correctly to cases needing most, some, or no attention remain unknown? Until there is a reliable and valid way for determining for which families services are most urgently needed, are many reforms in CPS at risk of not producing the outcomes desired? 4. Are there other unintended consequences of either accepting or rejecting DR that might not have been considered? Our current perspective is to state the obvious and point out that rarely are scientifically or "evidence-based" changes in practice achieved or discredited in a decade or two, much more a scant few years. Breathing deeply from time to time, and even pausing for reflection once in awhile, are useful habits for taking on long-range and difficult human endeavors.

Demand Response Resource Quantification with Detailed Building Energy Models

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

Hale, Elaine; Horsey, Henry; Merket, Noel

Demand response is a broad suite of technologies that enables changes in electrical load operations in support of power system reliability and efficiency. Although demand response is not a new concept, there is new appetite for comprehensively evaluating its technical potential in the context of renewable energy integration. The complexity of demand response makes this task difficult -- we present new methods for capturing the heterogeneity of potential responses from buildings, their time-varying nature, and metrics such as thermal comfort that help quantify likely acceptability of specific demand response actions. Computed with an automated software framework, the methods are scalable.

United States Air Force Research Initiation Program for 1988. Volume 3

DTIC Science & Technology

1990-04-01

Assignment for Dr. Kenneth M. Sobel Flight Control Design 210-9MG-035 90 Comparative Burning Rates and Duplex Dr. Forrest Thomas (1987) Loads of Solid...Patterson Air Force Base. The test configuration has been designed for injecting fuel droplets in a well controlled laminar on well-characterized turbulent...its counter response may be significant, our system has thus achieved some measure of control over when non -critical processing is actually performed

Detailed Measurements of the Aeroelastic Response of a Rigid Coaxial Rotor in Hover

DTIC Science & Technology

2017-08-11

included: hover testing of single and CCR rotors (Year 1), deformation measurement and modal identification of rotor blades in the non -rotating and...the rotor blades, as well as the detailed experimental data were shared with Dr. Rajneesh Singh and Dr. Hao Kang at Vehicle Technology Directorate...VTD), Aberdeen Proving Grounds, MD. In this way, the experimental data could be used to validate US Army comprehensive analysis tools, specifically

Welding technologies as applied to nuclear manufacturing

NASA Astrophysics Data System (ADS)

Roper, J. R.

1992-10-01

This is the trip report of John R. Roper, who traveled to England 25 Sep. through 8 Oct. 1992. Dr. Roper attended the US/UK JOWOG 22-D Joining Technical Exchange meeting and gave a presentation on Welding Finite Element Analysis and the Precision Joining Center at the Atomic Weapons Establishment in Aldermaston, United Kingdom. Dr. Roper also toured the Welding Institute in Abington, UK and discussed technology exchange of weld thermal and mechanical material responses.

Effect of chronic unpredictable stress on short term dietary restriction and its modulation by multivitamin-mineral supplementation.

PubMed

Hasan, Shirin; Fatima, Naureen; Bilal, Nayeem; Suhail, Nida; Fatima, Sabiha; Morgan, Enas N; Aldebasy, Yousef; Alzohairy, Mohammad A; Banu, Naheed

2013-06-01

Dietary restriction (DR) lowers steady-state levels of oxidative stress and alters behavioral, physiological and biochemical responses in mammals. However, various factors effect its application in humans like socio-cultural, appetite and the daily life stress. Physiological and psychological stress owing to fast-paced lifestyles, translates into oxidative stress. In this work, the role of chronic unpredictable stress (CUS) on the effects of short term DR in mice in terms of biochemical and oxidative stress parameters was investigated. Further, the modulatory role of multivitamin-mineral supplement (MVM) on CUS and DR induced biochemical changes was studied to delineate the role of micronutrient supplementation. DR treatment increased the antioxidant status in the circulation and liver of mice but in the presence of chronic stressors there was a significant shift towards the pro-oxidant state. A decrease was found in the activities of antioxidant enzymes superoxide dismutase, catalase, and glutathione-S-transferase and glutathione reductase in the rats exposed to CUS with DR (CUS+DR), with an increased malondialdehyde and a decreased glutathione (GSH) levels as compared to the controls. Liver function enzymes-glutamate oxaloacetate transaminase and glutamate pyruvate transaminase were increased and a significant DNA damage was observed. Oral MVM supplement significantly improved this oxidative deterioration. Hence, MVM supplementation appears to potentially offer an effective intervention in the DR regimen to combat daily life physical and mental stress. Copyright © 2013 Elsevier Ltd. All rights reserved.

DR2 blocker thioridazine: A promising drug for ovarian cancer therapy

PubMed Central

Yong, Min; Yu, Tinghe; Tian, Si; Liu, Shuaibin; Xu, Jiao; Hu, Jianguo; Hu, Lina

2017-01-01

Dopamine receptor 2 (DR2) may be a biomarker for various types of cancer. Ovarian cancer cells overexpress DR2; therefore, blocking DR2 may be a novel treatment strategy for ovarian cancer. Thioridazine, a DR2 blocker, has antineoplastic activity in a variety of cancer cells. In view of the requirement for novel therapeutic agents in ovarian cancer, the present study aimed to determine the potential effects of thioridazine in vitro and in vivo. It was revealed that the DR2 blocker thioridazine induced cell death in a dose-dependent manner in ovarian cancer cells. Thioridazine treatment induced apoptosis and autophagy, which may be attributed to an increased level of reactive oxygen species and associated DNA damage. Additionally, the expression of various proteins increased with oxidative stress, including nuclear factor E2-related factor 2, which is a pivotal transcriptional factor involved in cellular responses to oxidative stress. Heme oxygenase 1, NAPDH quinone dehydrogenase 1 and hypoxia inducible factor-1α and phosphorylated (p)-protein kinase B expression was significantly decreased, and the expression level of p-extracellular signal-related kinases and p-P38 was increased. Using 3-methyl adenine to inhibit autophagy caused the rate of apoptosis to increase. Thioridazine inhibited the growth of SKOV3 xenografts in nude mice. The present study demonstrated that the DR2 blocker thioridazine exhibited anticancer effects in vitro and in vivo, suggesting that thioridazine may be used as a potential drug in ovarian cancer therapy. PMID:29344260

49 CFR 37.77 - Purchase or lease of new non-rail vehicles by public entities operating a demand responsive...

Code of Federal Regulations, 2014 CFR

2014-10-01

... public entities operating a demand responsive system for the general public. 37.77 Section 37.77...-rail vehicles by public entities operating a demand responsive system for the general public. (a) Except as provided in this section, a public entity operating a demand responsive system for the general...

49 CFR 37.77 - Purchase or lease of new non-rail vehicles by public entities operating a demand responsive...

Code of Federal Regulations, 2010 CFR

2010-10-01

... public entities operating a demand responsive system for the general public. 37.77 Section 37.77...-rail vehicles by public entities operating a demand responsive system for the general public. (a) Except as provided in this section, a public entity operating a demand responsive system for the general...

49 CFR 37.77 - Purchase or lease of new non-rail vehicles by public entities operating a demand responsive...

Code of Federal Regulations, 2011 CFR

2011-10-01

... public entities operating a demand responsive system for the general public. 37.77 Section 37.77...-rail vehicles by public entities operating a demand responsive system for the general public. (a) Except as provided in this section, a public entity operating a demand responsive system for the general...

49 CFR 37.77 - Purchase or lease of new non-rail vehicles by public entities operating a demand responsive...

Code of Federal Regulations, 2012 CFR

2012-10-01

... public entities operating a demand responsive system for the general public. 37.77 Section 37.77...-rail vehicles by public entities operating a demand responsive system for the general public. (a) Except as provided in this section, a public entity operating a demand responsive system for the general...

Economics of Future Growth in Photovoltaics Manufacturing

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

Basore, Paul A.; Chung, Donald; Buonassisi, Tonio

2015-06-14

The past decade's record of growth in the photovoltaics manufacturing industry indicates that global investment in manufacturing capacity for photovoltaic modules tends to increase in proportion to the size of the industry. The slope of this proportionality determines how fast the industry will grow in the future. Two key parameters determine this slope. One is the annual global investment in manufacturing capacity normalized to the manufacturing capacity for the previous year (capacity-normalized capital investment rate, CapIR, units $/W). The other is how much capital investment is required for each watt of annual manufacturing capacity, normalized to the service life ofmore » the assets (capacity-normalized capital demand rate, CapDR, units $/W). If these two parameters remain unchanged from the values they have held for the past few years, global manufacturing capacity will peak in the next few years and then decline. However, it only takes a small improvement in CapIR to ensure future growth in photovoltaics. Any accompanying improvement in CapDR will accelerate that growth.« less

Decision regret in men undergoing dose-escalated radiation therapy for prostate cancer.

PubMed

Steer, Anna N; Aherne, Noel J; Gorzynska, Karen; Hoffman, Matthew; Last, Andrew; Hill, Jacques; Shakespeare, Thomas P

2013-07-15

Decision regret (DR) is a negative emotion associated with medical treatment decisions, and it is an important patient-centered outcome after therapy for localized prostate cancer. DR has been found to occur in up to 53% of patients treated for localized prostate cancer, and it may vary depending on treatment modality. DR after modern dose-escalated radiation therapy (DE-RT) has not been investigated previously, to our knowledge. Our primary aim was to evaluate DR in a cohort of patients treated with DE-RT. We surveyed 257 consecutive patients with localized prostate cancer who had previously received DE-RT, by means of a validated questionnaire. There were 220 responses (85.6% response rate). Image-guided intensity modulated radiation therapy was given in 85.0% of patients and 3-dimensional conformal radiation therapy in 15.0%. Doses received included 73.8 Gy (34.5% patients), 74 Gy (53.6%), and 76 Gy (10.9%). Neoadjuvant androgen deprivation (AD) was given in 51.8% of patients and both neoadjuvant and adjuvant AD in 34.5%. The median follow-up time was 23 months (range, 12-67 months). In all, 3.8% of patients expressed DR for their choice of treatment. When asked whether they would choose DE-RT or AD again, only 0.5% probably or definitely would not choose DE-RT again, compared with 8.4% for AD (P<.01). Few patients treated with modern DE-RT express DR, with regret appearing to be lower than in previously published reports of patients treated with radical prostatectomy or older radiation therapy techniques. Patients experienced more regret with the AD component of treatment than with the radiation therapy component, with implications for informed consent. Further research should investigate regret associated with individual components of modern therapy, including AD, radiation therapy and surgery. Crown Copyright © 2013. Published by Elsevier Inc. All rights reserved.

Decision Regret in Men Undergoing Dose-Escalated Radiation Therapy for Prostate Cancer

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

Steer, Anna N.; Aherne, Noel J., E-mail: noel.aherne@ncahs.health.nsw.gov.au; Rural Clinical School Faculty of Medicine, University of New South Wales, Coffs Harbour

2013-07-15

Purpose: Decision regret (DR) is a negative emotion associated with medical treatment decisions, and it is an important patient-centered outcome after therapy for localized prostate cancer. DR has been found to occur in up to 53% of patients treated for localized prostate cancer, and it may vary depending on treatment modality. DR after modern dose-escalated radiation therapy (DE-RT) has not been investigated previously, to our knowledge. Our primary aim was to evaluate DR in a cohort of patients treated with DE-RT. Methods and Materials: We surveyed 257 consecutive patients with localized prostate cancer who had previously received DE-RT, by meansmore » of a validated questionnaire. Results: There were 220 responses (85.6% response rate). Image-guided intensity modulated radiation therapy was given in 85.0% of patients and 3-dimensional conformal radiation therapy in 15.0%. Doses received included 73.8 Gy (34.5% patients), 74 Gy (53.6%), and 76 Gy (10.9%). Neoadjuvant androgen deprivation (AD) was given in 51.8% of patients and both neoadjuvant and adjuvant AD in 34.5%. The median follow-up time was 23 months (range, 12-67 months). In all, 3.8% of patients expressed DR for their choice of treatment. When asked whether they would choose DE-RT or AD again, only 0.5% probably or definitely would not choose DE-RT again, compared with 8.4% for AD (P<.01). Conclusion: Few patients treated with modern DE-RT express DR, with regret appearing to be lower than in previously published reports of patients treated with radical prostatectomy or older radiation therapy techniques. Patients experienced more regret with the AD component of treatment than with the radiation therapy component, with implications for informed consent. Further research should investigate regret associated with individual components of modern therapy, including AD, radiation therapy and surgery.« less

Genes, blame and loss of control: is there a place in criminal law for a 'genetic defense'?

PubMed

Gavaghan, Colin; Bastani, Amir

2014-01-01

In 2002, Caspi and colleagues proposed that a specific gene by environment (GxE) interaction is related to antisocial tendencies. Since then, a substantial body of literature has examined the potential implications of such a correlation for the criminal justice system, and in particular, for the attribution of responsibility and blame that lies at the core of that system. It is probably accurate to say that the majority position among criminal theorists is that evidence of such a nature does not undermine or seriously challenge existing notions of responsibility, and could not constitute a full defense to a criminal charge - although it may have a role to play in sentencing. Less consideration, however, has been given to the role such evidence may play in so-called 'partial defenses' - those like diminished responsibility (DR), which serve not to exculpate the defendant entirely, but rather, to mitigate his responsibility for the criminal act. This paper aims to assess the most important feature of the Caspi Sudy - the low variant gene for the production of Monoamine Oxidase Acid A gene (MAOA-L) - and its possible role in a defense of DR. We argue that, following the approach of common law jurisdictions to analogous situations, there is no principled reason to exclude evidence of MAOA-L as a basis of DR.

Assessment of frequency specific auditory steady-state response using amplitude modulation with 2-order exponential envelope.

PubMed

Cevallos-Larrea, Pablo; Pereira, Thobias; Santos, Wagner; Frota, Silvana M; Infantosi, Antonio F; Ichinose, Roberto M; Tierra-Criollo, Carlos

2016-08-01

This study investigated the performance of Frequency Specific Auditory Steady-State Response (FS-ASSR) detection elicited by the amplitude modulated tone with 2-order exponential envelope (AM2), using objective response detection (ORD) techniques of Spectral F-Test (SFT) and Magnitude Squared Coherence (MSC). ASSRs from 24 normal hearing adults were obtained during binaural multi-tone stimulation of amplitude-modulation (AM) and AM2 at intensities of 60, 45 and 30 dBSPL. The carrier frequencies were 500, 1000, 2000, and 4000 Hz, modulated between 77 and 105 Hz. AM2 achieve FS-ASSR amplitudes higher than AM by 16%, 18% and 12% at 60, 45 and 30 dBSPL, respectively, with a major increase at 500 Hz (22.5%). AMS2PL increased the Detection Rate (DR) up to 8.3% at 500 Hz for 30 dBSPL, which is particularly beneficial for FS-ASSR detection near the hearing threshold. In addition, responses in 1000 and 4000 Hz were consistently increased. The MSC and SFT presented no differences in Detection Rate (DR). False Detection Rate (FDR) was close to 5% for both techniques and tones. Detection times to reach DR over 90% were 3.5 and 4.9 min at 60 and 45 dBSPL, respectively. Further investigation concerning efficient multiple FS-ASSR is still necessary, such as testing subjects with hearing loss.

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

Kim, Joyce Jihyun; Yin, Rongxin; Kiliccote, Sila

Open Automated Demand Response (OpenADR), an XML-based information exchange model, is used to facilitate continuous price-responsive operation and demand response participation for large commercial buildings in New York who are subject to the default day-ahead hourly pricing. We summarize the existing demand response programs in New York and discuss OpenADR communication, prioritization of demand response signals, and control methods. Building energy simulation models are developed and field tests are conducted to evaluate continuous energy management and demand response capabilities of two commercial buildings in New York City. Preliminary results reveal that providing machine-readable prices to commercial buildings can facilitate bothmore » demand response participation and continuous energy cost savings. Hence, efforts should be made to develop more sophisticated algorithms for building control systems to minimize customer's utility bill based on price and reliability information from the electricity grid.« less

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

Piette, Mary Ann

California needs new, responsive, demand-side energy technologies to ensure that periods of tight electricity supply on the grid don't turn into power outages. Led by Berkeley Lab's Mary Ann Piette, the California Energy Commission (through its Public Interest Energy Research Program) has established a Demand Response Research Center that addresses two motivations for adopting demand responsiveness: reducing average electricity prices and preventing future electricity crises. The research seeks to understand factors that influence "what works" in Demand Response. Piette's team is investigating the two types of demand response, load response and price response, that may influence and reduce the usemore » of peak electric power through automated controls, peak pricing, advanced communications, and other strategies.« less

Saving Power at Peak Hours (LBNL Science at the Theater)

ScienceCinema

Piette, Mary Ann [Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)

2018-05-23

California needs new, responsive, demand-side energy technologies to ensure that periods of tight electricity supply on the grid don't turn into power outages. Led by Berkeley Lab's Mary Ann Piette, the California Energy Commission (through its Public Interest Energy Research Program) has established a Demand Response Research Center that addresses two motivations for adopting demand responsiveness: reducing average electricity prices and preventing future electricity crises. The research seeks to understand factors that influence "what works" in Demand Response. Piette's team is investigating the two types of demand response, load response and price response, that may influence and reduce the use of peak electric power through automated controls, peak pricing, advanced communications, and other strategies.

Estimating Ridership of Rural Demand-Response Transit Services for the General Public : 21177060-NCTR-NDSU08.

DOT National Transportation Integrated Search

2016-08-01

The objective of this study is to develop a model for estimating demand for rural demand-response transit services for the general public. Lack of data for demand-response service characteristics and geographic coverage has limited the development of...

Opportunities for Energy Efficiency and Automated Demand Response in Industrial Refrigerated Warehouses in California

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

Lekov, Alex; Thompson, Lisa; McKane, Aimee

2009-05-11

This report summarizes the Lawrence Berkeley National Laboratory's research to date in characterizing energy efficiency and open automated demand response opportunities for industrial refrigerated warehouses in California. The report describes refrigerated warehouses characteristics, energy use and demand, and control systems. It also discusses energy efficiency and open automated demand response opportunities and provides analysis results from three demand response studies. In addition, several energy efficiency, load management, and demand response case studies are provided for refrigerated warehouses. This study shows that refrigerated warehouses can be excellent candidates for open automated demand response and that facilities which have implemented energy efficiencymore » measures and have centralized control systems are well-suited to shift or shed electrical loads in response to financial incentives, utility bill savings, and/or opportunities to enhance reliability of service. Control technologies installed for energy efficiency and load management purposes can often be adapted for open automated demand response (OpenADR) at little additional cost. These improved controls may prepare facilities to be more receptive to OpenADR due to both increased confidence in the opportunities for controlling energy cost/use and access to the real-time data.« less

Prevalence of Diabetic Retinopathy in Urban Slums: The Aditya Jyot Diabetic Retinopathy in Urban Mumbai Slums Study-Report 2.

PubMed

Sunita, Mohan; Singh, Arvind Kumar; Rogye, Ashwini; Sonawane, Manish; Gaonkar, Ravina; Srinivasan, Radhika; Natarajan, Sundaram; Stevens, Fred C J; Scherpbier, A J J A; Kumaramanickavel, Govindasamy; McCarty, Catherine

2017-10-01

The aims of the study were to estimate the prevalence of diabetic retinopathy (DR) and enumerate history-based risk factors in the urban slums of Western India. The population-based study was conducted in seven wards of Mumbai urban slums, where we screened 6569 subjects of ≥ 40 years age, with a response rate of 98.4%, for type 2 diabetes mellitus (T2DM) based on American Diabetes Association criteria. All subjects with T2DM underwent dilated 30° seven-field stereo-fundus-photography for DR severity grading based on modified Airlie House classification. A multivariate logistic regression model was used to assess the correlation of DR with the history-based risk factors. The prevalence of DR in the general population of Mumbai urban slums was 1.41% (95% CI 0.59-2.23) and in the T2DM population it was 15.37% (95% CI 8.87-21.87). The positive associations with DR were the longer duration of DM (≥ 11 years: OR, 12.77; 95% CI 2.93-55.61) and male gender (OR, 2.05; 95% CI 1.08-3.89); increasing severity of retinopathy was also significantly associated with longer duration of DM (p < 0.001). However, history of hypertension, family history of DM, consanguineous marriage and migration status were not associated with DR in the study population. The prevalence of DR in the general population and T2DM subjects were 1.41% and 15.37% respectively in Mumbai urban slums. Duration of DM and male gender were significantly associated with DR. The slums in Western India show the trends of urban lifestyle influences similar to the rest of urban India.

Two-stage stochastic unit commitment model including non-generation resources with conditional value-at-risk constraints

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

Huang, Yuping; Zheng, Qipeng P.; Wang, Jianhui

2014-11-01

tThis paper presents a two-stage stochastic unit commitment (UC) model, which integrates non-generation resources such as demand response (DR) and energy storage (ES) while including riskconstraints to balance between cost and system reliability due to the fluctuation of variable genera-tion such as wind and solar power. This paper uses conditional value-at-risk (CVaR) measures to modelrisks associated with the decisions in a stochastic environment. In contrast to chance-constrained modelsrequiring extra binary variables, risk constraints based on CVaR only involve linear constraints and con-tinuous variables, making it more computationally attractive. The proposed models with risk constraintsare able to avoid over-conservative solutions butmore » still ensure system reliability represented by loss ofloads. Then numerical experiments are conducted to study the effects of non-generation resources ongenerator schedules and the difference of total expected generation costs with risk consideration. Sen-sitivity analysis based on reliability parameters is also performed to test the decision preferences ofconfidence levels and load-shedding loss allowances on generation cost reduction.« less

Preserving the national blood supply.

PubMed

Brittenham, G M; Klein, H G; Kushner, J P; Ajioka, R S

2001-01-01

This paper examines the current state of the blood supply in the US and focuses on the potential for augmenting blood availability by attention to the iron status of donors. Increasing demands are being made upon the national blood supply as rates of blood donation are declining, in part because of the loss of blood donors as a result of enhanced screening and testing procedures. Iron-related means of expanding the blood supply include the use of blood from individuals undergoing therapeutic phlebotomy for hereditary hemochromatosis and enhancing the retention and commitment of women of childbearing age as donors by using iron supplementation to prevent iron deficiency. In Section I, Dr. Klein discuss the circumstances responsible for a decline in the population of eligible donors, including public attitudes toward donation, factors influencing the retention of donors by blood centers, and the effects of increased screening and testing to maintain the safety of the blood supply. In Section II, Drs. Kushner and Ajioka focus on the consequences of the decision by the US Food and Drug Administration (FDA) to develop recommendations to permit blood centers to collect blood from patients with hereditary hemochromatosis and to distribute this blood obtained without disease labeling if all other screening and testing procedures are passed. After summarizing the pathophysiology of hereditary hemochromatosis, the use by blood centers of blood obtained from heterozygotes and homozygotes for hereditary hemochromatosis is considered. In Section III, Dr. Brittenham reviews the use of low dose, short-term carbonyl iron supplementation for women donors of childbearing age. Replacing the iron lost at donation can help prevent iron deficiency in women of childbearing age and, by decreasing deferral, enhance the retention and commitment of women who give blood regularly. He emphasizes the use by blood centers of iron-related means to enhance recruitment and retention of blood donors.

76 FR 78227 - Notice of Request for Extension of Approval of an Information Collection; Emergency Management...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-16

...] Notice of Request for Extension of Approval of an Information Collection; Emergency Management Response... approval of an information collection associated with the Emergency Management Response System. DATES: We...: For information on the Emergency Management Response System, contact Dr. Steven Finch, Senior Staff...

Increased expression of activation antigens on CD8+ T lymphocytes in Myalgic Encephalomyelitis/chronic fatigue syndrome: inverse associations with lowered CD19+ expression and CD4+/CD8+ ratio, but no associations with (auto)immune, leaky gut, oxidative and nitrosative stress biomarkers.

PubMed

Maes, Michael; Bosmans, Eugene; Kubera, Marta

2015-01-01

There is now evidence that specific subgroups of patients with Myalgic Encephalomyelitis / chronic fatigue syndrome (ME/CFS) suffer from a neuro-psychiatric-immune disorder. This study was carried out to delineate the expression of the activation markers CD38 and human leukocyte antigen (HLA) DR on CD4+ and CD8+ peripheral blood lymphocytes in ME/CFS. Proportions and absolute numbers of peripheral lymphocytes expressing CD3+, CD19+, CD4+, CD8+, CD38+ and HLA-DR+ were measured in ME/CFS (n=139), chronic fatigue (CF, n=65) and normal controls (n=40). The proportions of CD3+, CD8+, CD8+CD38+ and CD8+HLA-DR+ were significantly higher in ME/CFS patients than controls, while CD38+, CD8+CD38+, CD8+HLA-DR+ and CD38+HLA-DR+ were significantly higher in ME/CFS than CF. The percentage of CD19+ cells and the CD4+/CD8+ ratio were significantly lower in ME/CFS and CF than in controls. There were highly significant inverse correlations between the increased expression of CD38+, especially that of CD8+CD38+, and the lowered CD4+/CD8+ ratio and CD19+ expression. There were no significant associations between the flow cytometric results and severity or duration of illness and peripheral blood biomarkers of oxidative and nitrosative stress (O&NS, i.e. IgM responses to O&N modified epitopes), leaky gut (IgM or IgA responses to LPS of gut commensal bacteria), cytokines (interleukin-1, tumor necrosis factor-α), neopterin, lysozyme and autoimmune responses to serotonin. The results support that a) increased CD38 and HLA-DR expression on CD8+ T cells are biomarkers of ME/CFS; b) increased CD38 antigen expression may contribute to suppression of the CD4+/CD8+ ratio and CD19+ expression; c) there are different immune subgroups of ME/CFS patients, e.g. increased CD8+ activation marker expression versus inflammation or O&NS processes; and d) viral infections or reactivation may play a role in a some ME/CFS patients.

29 CFR 20.55 - Second and subsequent notifications.

Code of Federal Regulations, 2010 CFR

2010-07-01

... second and subsequent demands for payment, if payment or other appropriate response is not received within the time specified by the initial demand. Unless a response to the first or second demand indicates that a further demand would be futile or the debtor's response does not require rebuttal, the...

Yellow fever vaccination elicits broad functional CD4+ T cell responses that recognize structural and nonstructural proteins.

PubMed

James, Eddie A; LaFond, Rebecca E; Gates, Theresa J; Mai, Duy T; Malhotra, Uma; Kwok, William W

2013-12-01

Yellow fever virus (YFV) can induce acute, life-threatening disease that is a significant health burden in areas where yellow fever is endemic, but it is preventable through vaccination. The live attenuated 17D YFV strain induces responses characterized by neutralizing antibodies and strong T cell responses. This vaccine provides an excellent model for studying human immunity. While several studies have characterized YFV-specific antibody and CD8(+) T cell responses, less is known about YFV-specific CD4(+) T cells. Here we characterize the epitope specificity, functional attributes, and dynamics of YFV-specific T cell responses in vaccinated subjects by investigating peripheral blood mononuclear cells by using HLA-DR tetramers. A total of 112 epitopes restricted by seven common HLA-DRB1 alleles were identified. Epitopes were present within all YFV proteins, but the capsid, envelope, NS2a, and NS3 proteins had the highest epitope density. Antibody blocking demonstrated that the majority of YFV-specific T cells were HLA-DR restricted. Therefore, CD4(+) T cell responses could be effectively characterized with HLA-DR tetramers. Ex vivo tetramer analysis revealed that YFV-specific T cells persisted at frequencies ranging from 0 to 100 cells per million that are detectable years after vaccination. Longitudinal analysis indicated that YFV-specific CD4(+) T cells reached peak frequencies, often exceeding 250 cells per million, approximately 2 weeks after vaccination. As frequencies subsequently declined, YFV-specific cells regained CCR7 expression, indicating a shift from effector to central memory. Cells were typically CXCR3 positive, suggesting Th1 polarization, and produced gamma interferon and other cytokines after reactivation in vitro. Therefore, YFV elicits robust early effector CD4(+) T cell responses that contract, forming a detectable memory population.

Yellow Fever Vaccination Elicits Broad Functional CD4+ T Cell Responses That Recognize Structural and Nonstructural Proteins

PubMed Central

James, Eddie A.; LaFond, Rebecca E.; Gates, Theresa J.; Mai, Duy T.; Malhotra, Uma

2013-01-01

Yellow fever virus (YFV) can induce acute, life-threatening disease that is a significant health burden in areas where yellow fever is endemic, but it is preventable through vaccination. The live attenuated 17D YFV strain induces responses characterized by neutralizing antibodies and strong T cell responses. This vaccine provides an excellent model for studying human immunity. While several studies have characterized YFV-specific antibody and CD8+ T cell responses, less is known about YFV-specific CD4+ T cells. Here we characterize the epitope specificity, functional attributes, and dynamics of YFV-specific T cell responses in vaccinated subjects by investigating peripheral blood mononuclear cells by using HLA-DR tetramers. A total of 112 epitopes restricted by seven common HLA-DRB1 alleles were identified. Epitopes were present within all YFV proteins, but the capsid, envelope, NS2a, and NS3 proteins had the highest epitope density. Antibody blocking demonstrated that the majority of YFV-specific T cells were HLA-DR restricted. Therefore, CD4+ T cell responses could be effectively characterized with HLA-DR tetramers. Ex vivo tetramer analysis revealed that YFV-specific T cells persisted at frequencies ranging from 0 to 100 cells per million that are detectable years after vaccination. Longitudinal analysis indicated that YFV-specific CD4+ T cells reached peak frequencies, often exceeding 250 cells per million, approximately 2 weeks after vaccination. As frequencies subsequently declined, YFV-specific cells regained CCR7 expression, indicating a shift from effector to central memory. Cells were typically CXCR3 positive, suggesting Th1 polarization, and produced gamma interferon and other cytokines after reactivation in vitro. Therefore, YFV elicits robust early effector CD4+ T cell responses that contract, forming a detectable memory population. PMID:24049183

SIZ1 Regulation of Phosphate Starvation-Induced Root Architecture Remodeling Involves the Control of Auxin Accumulation1[C][W][OA

PubMed Central

Miura, Kenji; Lee, Jiyoung; Gong, Qingqiu; Ma, Shisong; Jin, Jing Bo; Yoo, Chan Yul; Miura, Tomoko; Sato, Aiko; Bohnert, Hans J.; Hasegawa, Paul M.

2011-01-01

Phosphate (Pi) limitation causes plants to modulate the architecture of their root systems to facilitate the acquisition of Pi. Previously, we reported that the Arabidopsis (Arabidopsis thaliana) SUMO E3 ligase SIZ1 regulates root architecture remodeling in response to Pi limitation; namely, the siz1 mutations cause the inhibition of primary root (PR) elongation and the promotion of lateral root (LR) formation. Here, we present evidence that SIZ1 is involved in the negative regulation of auxin patterning to modulate root system architecture in response to Pi starvation. The siz1 mutations caused greater PR growth inhibition and LR development of seedlings in response to Pi limitation. Similar root phenotypes occurred if Pi-deficient wild-type seedlings were supplemented with auxin. N-1-Naphthylphthalamic acid, an inhibitor of auxin efflux activity, reduced the Pi starvation-induced LR root formation of siz1 seedlings to a level equivalent to that seen in the wild type. Monitoring of the auxin-responsive reporter DR5::uidA indicated that auxin accumulates in PR tips at early stages of the Pi starvation response. Subsequently, DR5::uidA expression was observed in the LR primordia, which was associated with LR elongation. The time-sequential patterning of DR5::uidA expression occurred earlier in the roots of siz1 as compared with the wild type. In addition, microarray analysis revealed that several other auxin-responsive genes, including genes involved in cell wall loosening and biosynthesis, were up-regulated in siz1 relative to wild-type seedlings in response to Pi starvation. Together, these results suggest that SIZ1 negatively regulates Pi starvation-induced root architecture remodeling through the control of auxin patterning. PMID:21156857

Environmental Compliance Assessment and Management System (ECAMP), U.S. Air Force - German Supplement

DTIC Science & Technology

1993-10-01

ECP, was Associate Investigator. Dr. Diane K. Mann, CECER-ECP, is Acting Team Leader. Dr. John T. Bandy is Acting Chief, CECER-EC, and William D. Goran...Officer. (1)(3) Officer must discharge certain responsibilities - works toward improved safety on the installation (BImSchG, Section 58b). - informs the...objects, glass or mineral fibers, or materials in the form of webs or boards, including associated drying facilities, when the following are used: a

Electromagnetic Inverse Problems Involving Distributions of Dielectric Mechanisms and Parameters

DTIC Science & Technology

2005-08-17

0220 and in part by the National Institute of Aerospace (NIA) and NASA under grant NIA/NCSU-03-01-2536-NC. The authors would like to thank Dr. Richard...Albanese of the AFRL, Brooks AFB, and Dr. William P. Winfree, NASA Langley Research Center, for their valuable comments and suggestions during the...foods investigated by time-domain reflectometry , J. Food Science 68 (2003), 1396-1403. [46] P.G. Petropoulos, On the time-domain response of Cole-Cole

Phoenix, a High-Performance UNIX with an Emphasis on Dynamic Modification, Real-Time Response and Survivability

DTIC Science & Technology

1990-01-12

Communications COM-28, (April 1980 ) 425-432. [6] Munch-Anderson, B. and T.U. Zahle, Scheduling According to Job Priority With Prevention of Deadlock and...Interconnection, IEEE Transactions on Communications COM-28, (April 1980 ) 425-432. (4] Cook, R.P., StarMod, A Language for Distributed Programming...Research Triangle Park, NC 27709-2211 Attention: Dr. David W. Hislop * Electronics Division 51 Dr. David W. Hislop Electronics Division U. S. Army Research

Australian Disaster Research Directory (Including Some Contributions from New Zealand). Provisional--1983.

DTIC Science & Technology

1983-06-01

storm surge, cyclone,fire) * social and physical effects of nuclear attack * volcanic hazards statistics of abnormal sea levels * management of high...strengths and weaknesses of these responses * Impact of environmental change on present and future disaster strategies SOME QUESTIONNAIRE STATISTICS Some of...James Cook Univ Black , Mr R G 99 Sen Lec, Civil Eng, QIT Blackman. Dr D R 86 Sen Lec, Dept Mech Eng, V---ash Blong, Dr Russell 80 Sen Lec, Earth

Role of Superoxide Dismutase in the Photochemical Response of Cultured RPE Cells to Laser Exposure at 413 nm

DTIC Science & Technology

2007-11-01

TX 78228 Optical Radiation Branch 2624 Louis Bauer Dr. Brooks City-Base, TX 78235-5128 8. PERFORMING ORGANIZATION REPORT NUMBER AFRL 711...Effectiveness Directorate Directed Energy Bioeffects Division Optical Radiation Branch 2624 Louis Bauer Dr. Brooks City-Base, TX 78235-5128 711 HPW...K, Coherent) was used for its 413-nm line. Verification of laser wavelength was performed with a spectrometer (Ocean Optics ). Figure 1 provides a

Community control of health services. Dr. Martin Luther King, Jr. Health Center's community management system.

PubMed

Tichy, N M; Taylor, J I

1976-01-01

This article presents the case of Dr. Martin Luther King Jr. Health Center's unique community management system in which neighborhood workers have been developed to assume managerial responsibilities and are directing the Center. The Martin Luther King Center experience is instructive because the Center was able to achieve significant community control by focusing primarily on the internal dimension of control, namely, management, without experiencing destructive conflicts and the deterioration of health services.

Meeting Jentschke

ScienceCinema

None

2018-05-18

After an introduction about the latest research and news at CERN, the DG W. Jentschke speaks about future management of CERN with two new general managers, who will be in charge for the next 5 years: Dr. J.B. Adams who will focus on the administration of CERN and also the construction of buildings and equipment, and Dr. L. Van Hove who will be responsible for research activities. The DG speaks about expected changes, shared services, different divisions and their leaders, etc.

Study of decolorisation of binary dye mixture by response surface methodology.

PubMed

Khamparia, Shraddha; Jaspal, Dipika

2017-10-01

Decolorisation of a complex mixture of two different classes of textile dyes Direct Red 81 (DR81) and Rhodamine B (RHB), simulating one of the most important condition in real textile effluent was investigated onto deoiled Argemone Mexicana seeds (A. Mexicana). The adsorption behaviour of DR81 and RHB dyes was simultaneously analyzed in the mixture using derivative spectrophotometric method. Central composite design (CCD) was employed for designing the experiments for this complex binary mixture where significance of important parameters and possible interactions were analyzed by response surface methodology (RSM). Maximum adsorption of DR81 and RHB by A. Mexicana was obtained at 53 °C after 63.33 min with 0.1 g of adsorbent and 8 × 10 -6  M DR81, 12 × 10 -6  M RHB with composite desirability of 0.99. The predicted values for percentage removal of dyes from the mixture were in good agreement with the experimental values with R 2 > 96% for both the dyes. CCD superimposed RSM confirmed that presence of different dyes in a solution created a competition for the adsorbent sites and hence interaction of dyes was one of the most important factor to be studied to simulate the real effluent. The adsorbent showed remarkable adsorption capacities for both the dyes in the mixture. Copyright © 2017 Elsevier Ltd. All rights reserved.

Molecular Mechanisms of Enhanced Bacterial Growth on Hexadecane with Red Clay.

PubMed

Jung, Jaejoon; Jang, In-Ae; Ahn, Sungeun; Shin, Bora; Kim, Jisun; Park, Chulwoo; Jee, Seung Cheol; Sung, Jung-Suk; Park, Woojun

2015-11-01

Red clay was previously used to enhance bioremediation of diesel-contaminated soil. It was speculated that the enhanced degradation of diesel was due to increased bacterial growth. In this study, we selected Acinetobacter oleivorans DR1, a soil-borne degrader of diesel and alkanes, as a model bacterium and performed transcriptional analysis using RNA sequencing to investigate the cellular response during hexadecane utilization and the mechanism by which red clay promotes hexadecane degradation. We confirmed that red clay promotes the growth of A. oleivorans DR1 on hexadecane, a major component of diesel, as a sole carbon source. Addition of red clay to hexadecane-utilizing DR1 cells highly upregulated β-oxidation, while genes related to alkane oxidation were highly expressed with and without red clay. Red clay also upregulated genes related to oxidative stress defense, such as superoxide dismutase, catalase, and glutaredoxin genes, suggesting that red clay supports the response of DR1 cells to oxidative stress generated during hexadecane utilization. Increased membrane fluidity in the presence of red clay was confirmed by fatty acid methyl ester analysis at different growth phases, suggesting that enhanced growth on hexadecane could be due to increased uptake of hexadecane coupled with upregulation of downstream metabolism and oxidative stress defense. The monitoring of the bacterial community in soil with red clay for a year revealed that red clay stabilized the community structure.

The TL1A/DR3/DcR3 pathway in autoimmune rheumatic diseases.

PubMed

Siakavellas, Spyros I; Sfikakis, Petros P; Bamias, Giorgos

2015-08-01

TNF-like cytokine 1A (TL1A) and its receptors, death receptor 3 (DR3) and decoy receptor 3 (DcR3) are members of the TNF and TNF receptor superfamilies of proteins, respectively. They constitute a cytokine system that actively interferes with the regulation of immune responses and may participate in the pathogenesis of autoimmune diseases. This review aims to present the current knowledge on the role of the TL1A/DR3/DcR3 system in the pathophysiology of autoimmune rheumatic diseases, with a focus on rheumatoid arthritis (RA). An extensive literature search was performed in the PubMed database using the following keywords: TL1A, death receptor 3, DR3, decoy receptor 3, DcR3, TNFSF15, TNFRSF25, and TNFSF6B. Studies were assessed and selected in view of their relevance to autoimmune rheumatic diseases. The TL1A/DR3/DcR3 axis is a novel immune pathway that participates in the pathogenesis of a variety of autoimmune rheumatic diseases. These molecules may be promising therapeutic targets for inflammatory arthritis. Copyright © 2015 Elsevier Inc. All rights reserved.

Neuroprotection as a Therapeutic Target for Diabetic Retinopathy.

PubMed

Hernández, Cristina; Dal Monte, Massimo; Simó, Rafael; Casini, Giovanni

2016-01-01

Diabetic retinopathy (DR) is a multifactorial progressive disease of the retina and a leading cause of vision loss. DR has long been regarded as a vascular disorder, although neuronal death and visual impairment appear before vascular lesions, suggesting an important role played by neurodegeneration in DR and the appropriateness of neuroprotective strategies. Upregulation of vascular endothelial growth factor (VEGF), the main target of current therapies, is likely to be one of the first responses to retinal hyperglycemic stress and VEGF may represent an important survival factor in early phases of DR. Of central importance for clinical trials is the detection of retinal neurodegeneration in the clinical setting, and spectral domain optical coherence tomography seems the most indicated technique. Many substances have been tested in animal studies for their neuroprotective properties and for possible use in humans. Perhaps, the most intriguing perspective is the use of endogenous neuroprotective substances or nutraceuticals. Together, the data point to the central role of neurodegeneration in the pathogenesis of DR and indicate neuroprotection as an effective strategy for treating this disease. However, clinical trials to determine not only the effectiveness and safety but also the compliance of a noninvasive route of drug administration are needed.

Neuroprotection as a Therapeutic Target for Diabetic Retinopathy

PubMed Central

Hernández, Cristina; Simó, Rafael

2016-01-01

Diabetic retinopathy (DR) is a multifactorial progressive disease of the retina and a leading cause of vision loss. DR has long been regarded as a vascular disorder, although neuronal death and visual impairment appear before vascular lesions, suggesting an important role played by neurodegeneration in DR and the appropriateness of neuroprotective strategies. Upregulation of vascular endothelial growth factor (VEGF), the main target of current therapies, is likely to be one of the first responses to retinal hyperglycemic stress and VEGF may represent an important survival factor in early phases of DR. Of central importance for clinical trials is the detection of retinal neurodegeneration in the clinical setting, and spectral domain optical coherence tomography seems the most indicated technique. Many substances have been tested in animal studies for their neuroprotective properties and for possible use in humans. Perhaps, the most intriguing perspective is the use of endogenous neuroprotective substances or nutraceuticals. Together, the data point to the central role of neurodegeneration in the pathogenesis of DR and indicate neuroprotection as an effective strategy for treating this disease. However, clinical trials to determine not only the effectiveness and safety but also the compliance of a noninvasive route of drug administration are needed. PMID:27123463

[Clinic of environmental pediatric care in a high complexity hospital].

PubMed

Gaioli, Marisa; Amoedo, Diego; González, Daniel

2014-12-01

Children environmental health is considered by The World Health Organization as one of the main challenges of Public Health during the Century XXI. They promote the development of programs that allow approaching, disclosure or mitigation of the impact of polluting agents on health at every level of pediatric attention. The Children Hospital "Prof. Dr. Juan P. Garrahan" has created an Environmental Health Office in order to address the demands of those patients with suspected or verified exposure to environmental risks. An Environmental Clinical History has been elaborated with this purpose.

AGARD Flight Test Techniques Series. Volume 17. Electronic Warfare Test and Evaluation. (Les Essais et l’Evaluation du Materiel de Guerre Electronique)

DTIC Science & Technology

2000-03-01

FRIENDLY DR ENEMY PLOY OFOR DEGSRADING, ENEUTALY IG DEGRA E,’ EUTRALIE, OR DESTR Y concepts, procedures, and techniques that apply generically to CMA...Association of Old Crows, September 1984 Price, Alfred, "The History of Electronic Warfare," Volume 2, Association of Old Crows, October 1989 Claxton, John...Canada Les demandes de documents RTO ou AGARD doivent comporter la denomination "RTO" ou "AGARD" selon le cas, suivie du numdro de s~rie (par exemple

Transcervical Inoculation with Chlamydia trachomatis Induces Infertility in HLA-DR4 Transgenic and Wild-Type Mice.

PubMed

Pal, Sukumar; Tifrea, Delia F; Zhong, Guangming; de la Maza, Luis M

2018-01-01

Chlamydia trachomatis is the leading cause of infection-induced infertility in women. Attempts to control this epidemic with screening programs and antibiotic therapy have failed. Currently, a vaccine to prevent C. trachomatis infections is not available. In order to develop an animal model for evaluating vaccine antigens that can be applied to humans, we used C. trachomatis serovar D (strain UW-3/Cx) to induce infertility in mice whose major histocompatibility complex class II antigen was replaced with the human leukocyte antigen DR4 (HLA-DR4). Transcervical inoculation of medroxyprogesterone-treated HLA-DR4 transgenic mice with 5 × 10 5 C. trachomatis D inclusion forming units (IFU) induced a significant reduction in fertility, with a mean number of embryos/mouse of 4.4 ± 1.3 compared to 7.8 ± 0.5 for the uninfected control mice ( P < 0.05). A similar fertility reduction was elicited in the wild-type (WT) C57BL/6 mice (4.3 ± 1.4 embryos/mouse) compared to the levels of the WT controls (9.1 ± 0.4 embryos/mouse) ( P < 0.05). Following infection, WT mice mounted more robust humoral and cellular immune responses than HLA-DR4 mice. As determined by vaginal shedding, HLA-DR4 mice were more susceptible to a transcervical C. trachomatis D infection than WT mice. To assess if HLA-DR4 transgenic and WT mice could be protected by vaccination, 10 4 IFU of C. trachomatis D was delivered intranasally, and mice were challenged transcervically 6 weeks later with 5 × 10 5 IFU of C. trachomatis D. As determined by severity and length of vaginal shedding, WT C57BL/6 and HLA-DR4 mice were significantly protected by vaccination. The advantages and limitations of the HLA-DR4 transgenic mouse model for evaluating human C. trachomatis vaccine antigens are discussed. Copyright © 2017 American Society for Microbiology.

Intermittent fasting combined with supplementation with Ayurvedic herbs reduces anxiety in middle aged female rats by anti-inflammatory pathways.

PubMed

Singh, Harpal; Kaur, Taranjeet; Manchanda, Shaffi; Kaur, Gurcharan

2017-08-01

Intermittent fasting-dietary restriction (IF-DR) is an increasingly popular intervention to promote healthy aging and delay age associated decline in brain functions. Also, the use of herbal interventions is gaining attention due to their non-pharmacological approach to treat several abnormalities and promote general health with least side effects. The present study was aimed to investigate the synergistic effects of IF-DR regimen with herbal supplementation on anxiety-like behavior and neuroinflammation in middle aged female rats. We used dried leaf powder of Withania somnifera and dried stem powder of Tinospora cordifolia for our study. The rats were divided into three groups: (1) Control group fed ad libitum (AL); (2) rats deprived of food for full day and fed ad libitum on every alternate day (IF-DR); and (3) IF-DR and herbal extract (DRH) group in which rats were fed ad libitum with herbal extract supplemented diet, every alternate day. Post regimen, the rats were tested for anxiety-like behavior and further used for study of key inflammatory molecules (NFκB, Iba1, TNFα, IL-1β, IL-6) and glial marker (GFAP) in hippocampus and piriform cortex regions of brain. The study was further extended to explore the effect of DRH regimen on stress response protein (HSP70) and calcium dependent regulators of synaptic plasticity (CaMKIIα, Calcineurin). Our data demonstrated that DRH regimen reduced anxiety-like behavior in middle age female rats and associated neuroinflammation by ameliorating key inflammatory cytokines and modulated stress response. The present data may provide scientific validation for anxiolytic and anti-inflammatory potential of herbal intervention combined with short term IF-DR regimen.

Dietary restriction but not angiotensin II type 1 receptor blockade improves DNA damage-related vasodilator dysfunction in rapidly aging Ercc1Δ/- mice.

PubMed

Wu, Haiyan; van Thiel, Bibi S; Bautista-Niño, Paula K; Reiling, Erwin; Durik, Matej; Leijten, Frank P J; Ridwan, Yanto; Brandt, Renata M C; van Steeg, Harry; Dollé, Martijn E T; Vermeij, Wilbert P; Hoeijmakers, Jan H J; Essers, Jeroen; van der Pluijm, Ingrid; Danser, A H Jan; Roks, Anton J M

2017-08-01

DNA damage is an important contributor to endothelial dysfunction and age-related vascular disease. Recently, we demonstrated in a DNA repair-deficient, prematurely aging mouse model ( Ercc1 Δ/- mice) that dietary restriction (DR) strongly increases life- and health span, including ameliorating endothelial dysfunction, by preserving genomic integrity. In this mouse mutant displaying prominent accelerated, age-dependent endothelial dysfunction we investigated the signaling pathways involved in improved endothelium-mediated vasodilation by DR, and explore the potential role of the renin-angiotensin system (RAS). Ercc1 Δ/- mice showed increased blood pressure and decreased aortic relaxations to acetylcholine (ACh) in organ bath experiments. Nitric oxide (NO) signaling and phospho-Ser 1177 -eNOS were compromised in Ercc1 Δ / - DR improved relaxations by increasing prostaglandin-mediated responses. Increase of cyclo-oxygenase 2 and decrease of phosphodiesterase 4B were identified as potential mechanisms. DR also prevented loss of NO signaling in vascular smooth muscle cells and normalized angiotensin II (Ang II) vasoconstrictions, which were increased in Ercc1 Δ/- mice. Ercc1 Δ/ - mutants showed a loss of Ang II type 2 receptor-mediated counter-regulation of Ang II type 1 receptor-induced vasoconstrictions. Chronic losartan treatment effectively decreased blood pressure, but did not improve endothelium-dependent relaxations. This result might relate to the aging-associated loss of treatment efficacy of RAS blockade with respect to endothelial function improvement. In summary, DR effectively prevents endothelium-dependent vasodilator dysfunction by augmenting prostaglandin-mediated responses, whereas chronic Ang II type 1 receptor blockade is ineffective. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

Pharmacokinetics, Safety, and 48-Week Efficacy of Oral Raltegravir in HIV-1–Infected Children Aged 2 Through 18 Years

PubMed Central

Nachman, Sharon; Zheng, Nan; Acosta, Edward P.; Teppler, Hedy; Homony, Brenda; Graham, Bobbie; Fenton, Terence; Xu, Xia; Wenning, Larissa; Spector, Stephen A.; Frenkel, Lisa M.; Alvero, Carmelita; Worrell, Carol; Handelsman, Edward; Wiznia, Andrew; Moultrie, Harry; Kindra, Gurpreet; Sanders, Margaret Ann; Williams, Ruth; Jensen, Jennifer; Acevedo, Midnela; Fabregas, Lizbeth; Jurgrau, Andrea; Foca, Marc; Higgins, Alice; Deville, Jaime G.; Nielsen-Saines, Karin; Carter, Michele F.; Swetnam, John; Wilson, Joan; Donnelly, Margaret; Akleh, Siham; Rigaud, Mona; Kaul, Aditya; Patel, Nehali; Gaur, Aditya; Utech, L. Jill; Cardoso, Edmundo; Moreira, Ana Maria; Santos, Breno; Bobat, Raziya; Mngqibisa, Rosie; Burey, Marlene; Abadi, Jacob; Rosenberg, Michael; Luzuriaga, Katherine; Picard, Donna; Pagano-Therrien, Jessica; Dittmer, Sylvia; Ndiweni, Hilda Ntatule; Patel, Amisha; DelRey, Michelle; McMullen-Jackson, Chivon; Paul, Mary E.; Melvin, Ann; Venema-Weiss, Corry; Lane, Jenna; Beneri, Christy; Ferraro, Denise; Infanzon, Erin; McAuley, James B; Aziz, Mariam; McNichols, Maureen; Pelton, Stephen; McLaud, Deb; Clarke, Diana; Zeichner, Steven; Akar, Arezou; Thompson, Deidre; Douglas, Steven D.; Rutstein, Richard M.; Vincent, Carol A.; Vachon, Mary Elizabeth; Cavallo, Martha; Purswani, Murli Udharam; Masheto, Gaerolwe; Ogwu, Anthony; Kakhu, Tebogo; Viani, Rolando M.; Darcey, Anita,; Norris, Kimberly; Burchett, Sandra K.; Kneut, Catherine; Karthas, Nancy; Casey, Denise; Emmanuel, Patricia; Lujan-Zilbermann, Jorge; Rana, Sohail; Houston, Patricia; Mengistab, Mulu; Rathore, Mobeen; Mirza, Ayesha; Gayton, Tabetha; Barr, Emily; Dunn, Jennifer; Hahn, Kerry; Eysallenne, Zulma; Howard, F. Sholar; Graham, Kathleen; Negra, Marinella Della; Queiroz, Wladimir; Lian, Yu Ching; Wara, Diane; Ruel, Ted; VanDyke, Russell; Reilly, Patricia; Bradford, Sheila; van Rensburg, Anita Janse; Dobbels, Els; Bester, Marietjie; Bamji, Mahrukh; Paul, Santa; Sarza, Mirala; Kovacs, Andrea; Homans, James; Spencer, LaShonda; Hofer, Cristna; Abreu, Thalita; Oliveira, Ricardo; Joao, Esau C.; Pinto, Jorge; Ferreira, Flavia; Kakehasi, Fabiana; Cervi, Maria Celia; Isaac, Marcia De Lima; Losso, Marcelo H.; Stankievich, Erica; Foradori, Irene; Tucker, Diane; Church, Joseph; Belzer, Marvin; Hopkins, Johns; Ellen, Jonathan; Agwu, Allison; Laurel, Borkovic

2014-01-01

Background. IMPAACT P1066 is a phase I/II open-label multicenter trial to evaluate pharmacokinetics, safety, tolerability, and efficacy of multiple raltegravir formulations in human immunodeficiency virus (HIV)–infected youth. Methods. Dose selection for each cohort (I: 12 to <19 years; II: 6 to <12 years; and III: 2 to <6 years) was based on review of short-term safety (4 weeks) and intensive pharmacokinetic evaluation. Safety data through weeks 24 and 48, and grade ≥3 or serious adverse events (AEs) were assessed. The primary virologic endpoint was achieving HIV RNA <400 copies/mL or ≥1 log10 reduction between baseline and week 24. Results. The targeted pharmacokinetic parameters (AUC0-12h and C12h) were achieved for each cohort, allowing dose selection for 2 formulations. Of 96 final dose subjects, there were 15 subjects with grade 3 or higher clinical AEs (1 subject with drug-related [DR] psychomotor hyperactivity and insomnia); 16 subjects with grade 3 or higher laboratory AEs (1 with DR transaminase elevation); 14 subjects with serious clinical AEs (1 with DR rash); and 1 subjects with serious laboratory AEs (1 with DR transaminase increased). There were no discontinuations due to AEs and no DR deaths. Favorable virologic responses at week 48 were observed in 79.1% of patients, with a mean CD4 increase of 156 cells/µL (4.6%). Conclusions. Raltegravir as a film-coated tablet 400 mg twice daily (6 to <19 years, and ≥25 kg) and chewable tablet 6 mg/kg (maximum dose 300 mg) twice daily (2 to <12 years) was well tolerated and showed favorable virologic and immunologic responses. Clinical Trials Registration NCT00485264. PMID:24145879

The impact of diabetic retinopathy on quality of life: qualitative findings from an item bank development project.

PubMed

Fenwick, Eva K; Pesudovs, Konrad; Khadka, Jyoti; Dirani, Mohamed; Rees, Gwyn; Wong, Tien Y; Lamoureux, Ecosse L

2012-12-01

Assessing the efficacy of treatment modalities for diabetic retinopathy (DR) from the patient's perspective is restricted due to a lack of a comprehensive patient-reported outcome measure. We are developing a DR-specific quality of life (QoL) item bank, and we report here on the qualitative results from the first phase of this project. Eight focus groups and 18 semi-structured interviews were conducted with 57 patients with DR. The sessions were transcribed verbatim and iteratively analysed using the constant comparative method and NVIVO software. Participants had a median age of 58 years (range 27-83 years). Twenty-seven (47%) participants had proliferative DR in the better eye, and 14 (25%) had clinically significant macular oedema. Nine QoL domains were identified, namely visual symptoms, ocular surface symptoms, vision-related activity limitation, mobility, emotional well-being, health concerns, convenience, social, and economic. Participants described many vision-related activity limitations, particularly under challenging lighting conditions; however, socioemotional issues were equally important. Participants felt frustrated due to their visual restrictions, concerned about further vision loss and had difficulty coping with this uncertainty. Restrictions on driving were pervasive, affecting transport, social life, relationships, responsibilities, work and independence. Patients with DR experience many socioemotional issues in addition to vision-related activity limitations. Data from this study will be used to generate data for a DR-specific QoL item bank.

[Pharmacologists in the camps in the Third Reich--part second].

PubMed

Labuzek, Krzysztof; Prusek, Katarzyna; Gonciarz, Maciej; Okopień, Boguslaw

2013-10-01

SS Hygiene Institute provided adequate funding for research on the treatment of mycobacterial infections, and two scientists who became famous in the subject were Dr. Waldemar Hoven (KL Buchenwald) and Dr. Kurt Heissmeyer (KL Neuengamme). They conducted researches not only on adult prisoners, but also on the Jewish children. Studies of tuberculosis were also conducted under the auspices of the German Medical Association by Dr. Rudolf Brachtel. In turn, Dr. Klaus Schilling dealt with the treatment and immunoprophylaxis of malaria. He tested such substances, as pyramidon, aspirin, quinine and atebrin on more than 1200 prisoners. These sulfonamide-derived drugs, were also studied by prof. Karl Gebhardt and Dr. Fritz Fischer. They assessed the efficacy of these drugs in the treatment of "dirty" wounds incurred by German soldiers. Dr. Heinrich Schutz, Karl Babor and Waldemar Wolter they were enthusiasts in so-called biochemical therapy, based on the use of substances of natural origin, such as salt. After termination of War, during the Nuremberg Trials, many of them evaded responsibility, they were running medical practices, some were publishing. However, despite those facts, trials of Nazi war criminals were not result less, they opened world's eyes for the necessity of clarifying rudiments of human subject research, they gave foundations to define records like The Convention for the Protection of Human Rights and Dignity of the Human Being with regard to the Application of Biology and Medicine or Good Clinical Practice.

STD / AIDS prevention: new challenges for family planning programs.

PubMed

Williamson, N; Townsend, S

1991-12-01

Family planning (FP) professionals and programs are increasingly called upon to respond to increasing rates of sexually transmitted diseases (STD) and AIDS. While structural and ideological readjustment to meet these demands may seem problematic for some programs, the AIDS epidemic allows the opportunity for programs to expand into preventive health activities. Dr. Nancy Williamson, Director of Family Health International's Division of Program Evaluation and 1 of the authors of the World Health Organization's guidelines on family planning and AIDS, responds to questions most frequently posed by FP providers considering the need for and process of FP program restructuring. She holds that programmatic expansion for the prevention of HIV infection enhances the capability to provide good contraceptive services. FP programs are not expected to abandon their central missions of preventing unwanted pregnancies, but to engage in both the prevention of STD infection and unwanted pregnancies where possible. Sharing responsible sex behavior and the condom as common means of prevention, these 2 missions are far from mutually exclusive. The AIDS epidemic has impacted upon FP programs in a number of ways. Increased demand for condoms has been observed in countries with high levels of HIV seropositivity, greater concern has been placed upon counseling and sterile procedures, view have been altered to accept this dual role of contraception, and universal precautions for the protection of both client and workers from infection are of greater importance. Promoting the consistent use of condoms for the prevention of STDs has proved more challenging than promoting for contraceptive uses. Gaining the legitimacy of condoms among married couples while they are also promoted among high-risk groups also remains difficult. On other issues, promoting the routine use of 2 temporary methods is not recommended, questions must be posed to determine clients' risk status for infection, counseling and services should be provided to those HIV+, and alternative funding sources may need to be sought for FP program expansion. Arguments for and against such expansion are discussed. Most of sub-Saharan Africa, the Caribbean, and Thailand are in most serious need of programmatic changes, India and most of Central and South American need some changes, and other areas would benefit from minor changes. Dr. Williamson finally considers how programs should be modified, changes made thus far by programs, and suggests what programs may do to enhance their capability to provide contraceptive services.

History of the Kolff Laboratory turbine driven electrohydraulic artificial heart.

PubMed

Topaz, S R; Flinders, T; Topaz, H A; Jones, D

1998-11-01

The concept of an electrically powered total artificial heart has been pursued by Dr. Kolff and his associates since the 1960s. Since the 1980s these efforts have been concentrated upon the development of the electrohydraulic total artificial heart, a turbine pump powered by a brushless DC motor. Dr. Kolff realized the benefits of pulsatile flow and device response to Starling's Law, and these concepts have formed the basis of subsequent design decisions. Design iterations have both solved existing problems and exposed new challenges. The current device design is greatly improved over early attempts due to the incorporation of technologies that have recently become available as the result of progress in the fields of materials and electronics and due to the lessons learned over many years of research under the guidance of Dr. Kolff. This article describes, from its inception, the last major research project of Dr. Kolff prior to his retirement. The discussion centers around development, problems and their solutions, and the reasoning for given solutions.

12 CFR 602.23 - Responses to demands served on FCA employees.

Code of Federal Regulations, 2010 CFR

2010-01-01

... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Responses to demands served on FCA employees. 602.23 Section 602.23 Banks and Banking FARM CREDIT ADMINISTRATION ADMINISTRATIVE PROVISIONS RELEASING....23 Responses to demands served on FCA employees. (a) An employee served with a demand or a subpoena...

Jim Starnes' Contributions to Residual Strength Analysis Methods for Metallic Structures

NASA Technical Reports Server (NTRS)

Young, Richard D.; Rose, Cheryl A.; Harris, Charles E.

2005-01-01

A summary of advances in residual strength analyses methods for metallic structures that were realized under the leadership of Dr. James H. Starnes, Jr., is presented. The majority of research led by Dr. Starnes in this area was conducted in the 1990's under the NASA Airframe Structural Integrity Program (NASIP). Dr. Starnes, respectfully referred to herein as Jim, had a passion for studying complex response phenomena and dedicated a significant amount of research effort toward advancing damage tolerance and residual strength analysis methods for metallic structures. Jim's efforts were focused on understanding damage propagation in built-up fuselage structure with widespread fatigue damage, with the goal of ensuring safety in the aging international commercial transport fleet. Jim's major contributions in this research area were in identifying the effects of combined internal pressure and mechanical loads, and geometric nonlinearity, on the response of built-up structures with damage. Analytical and experimental technical results are presented to demonstrate the breadth and rigor of the research conducted in this technical area. Technical results presented herein are drawn exclusively from papers where Jim was a co-author.

Critical role of surfactants in the formation of digestively-ripened, ultra-small (r<2 nm) copper oxide quantum dots

NASA Astrophysics Data System (ADS)

Talluri, Bhusankar; Prasad, Edamana; Thomas, Tiju

2018-04-01

Synthesis of ultra-small (r < 2 nm) and monodispersed semiconductor quantum dots (QDs) have gained considerable attention due to their wide range of applications, ranging from photovoltaics to sensing. Digestive ripening (DR), a method for preparing uniformly-sized particles is critically influenced by nature and concentrations of the starting materials, solvent, and surfactant. To better understand the DR process there is a need to study the effect of each synthetic parameter. In this work, we investigate the effect of surfactant on a ceramic-DR process, with copper oxide as the chosen material. To study the influence of surfactant; aminoalcohols (triethanolamine, diethanolamine, monoethanolamine), alkylamines (ethyl amine) and aqua ligands are chosen. Digestively ripened quantum dots (QDs) are formed in case of all surfactants except ethyl amine and water. Aminoalchols based surfactants which contain both hydroxyl and amine moieties are efficient ligands (due to their chelation ability) for achieving DR. With the increase of denticity of the ligand, average size of QDs do not vary; however the variance in size does. QDs formed using aminoalchols are more monodispersed when compared to alkyl amine and aqua ligand systems. Furthermore, absorption and photoluminescence spectra suggest that choice of surfactant is important for achieving DR in ceramic nanostructures (when compared to other parameters). Hard-soft-acid-base-interactions between surfactant and copper oxide seem primarily responsible for the observed DR in copper oxide QDs. The absorption and photoluminescence spectra indicate that the energy migration and relaxation pathways taking place in DR QDs depend on the type of capping agent used.

Inflammatory factors mediate vulnerability to a social stress-induced depressive-like phenotype in passive coping rats

PubMed Central

Wood, Susan K.; Wood, Christopher S.; Lombard, Calliandra M.; Lee, Catherine S.; Zhang, Xiao-Yan; Finnell, Julie E.; Valentino, Rita J.

2014-01-01

Background Coping strategy impacts susceptibility to psychosocial stress. The locus coeruleus (LC) and dorsal raphe (DR) are monoamine nuclei that are implicated in stress-related disorders. This study was designed to identify genes in these nuclei that distinguish active and passive coping strategies in response to social stress. Methods Rats were exposed to repeated resident-intruder stress and coping strategy determined. Gene and protein expression in the LC and DR were determined by PCR array, ELISA, and compared between active and passive stress coping and unstressed rats. The effect of daily IL-1 receptor antagonist (IL-1ra, ICV) prior to stress on anhedonia was also determined. Results Rats exhibited passive or active coping strategies based on a short (SL) or longer latency (LL) to assume a defeat posture, respectively. Stress differentially regulated 19 and 26 genes in the LC and DR of SL and LL rats, respectively, many of which encoded for inflammatory factors. Notably, IL1β was increased in SL and decreased in LL rats in both the LC and DR. Protein changes were generally consistent with a proinflammatory response to stress in SL rats selectively. Stress produced anhedonia selectively in SL rats and this was prevented by IL-1ra, consistent with a role for IL1β in stress vulnerability. Conclusions This study highlighted distinctions in gene expression related to coping strategy in response to social stress. Passive coping was associated with a bias towards pro-inflammatory processes, particularly IL1β, whereas active coping and resistance to stress-related pathology was associated with suppression of inflammatory processes. PMID:25676490

Digit ratio (2D:4D) and salivary testosterone, oestradiol and cortisol levels under challenge: Evidence for prenatal effects on adult endocrine responses.

PubMed

Crewther, Blair; Cook, Christian; Kilduff, Liam; Manning, John

2015-08-01

Digit ratio (2D:4D) is a marker for prenatal sex steroids and a correlate of sporting performance. This association may exist because low 2D:4D is linked to high prenatal levels of testosterone (T) and low oestrogens (E). It was recently suggested that low 2D:4D, and particularly low right-left 2D:4D (or Dr-l), is a marker for T changes in response to physical and aggressive challenges. If correct, this link may in part explain the association between 2D:4D and sports performance. We tested this hypothesis in adults. Three experimental treatments were completed using a randomised, cross-over design; (i) cycle sprints plus an aggressive video (S+V), (ii) aggressive video plus cycle sprints (V+S), and (iii) a control session. 24 healthy adults (12 men and 12 women). Salivary T, oestradiol (E2) and cortisol (C) levels were measured on six occasions across each session and pooled for analysis. The S+V treatment was associated with a rise in T and C levels, and Dr-l was significantly and negatively correlated with T and E2 with these effects confined to men. The right 2D:4D and Dr-l were also negatively correlated with the T/C ratio and Dr-l negatively related to the E2/C ratio in men during the S+V treatment. We suggest that the hormonal responses to a challenge are programmed by prenatal levels of T and E with possible links to sporting performance in adulthood. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Prevalence and determinants of undiagnosed diabetic retinopathy and vision-threatening retinopathy in a multiethnic Asian cohort: the Singapore Epidemiology of Eye Diseases (SEED) study.

PubMed

Huang, Olivia S; Tay, Wan Ting; Ong, Peng Guan; Sabanayagam, Charumathi; Cheng, Ching-Yu; Tan, Gavin S; Cheung, Gemmy C M; Lamoureux, Ecosse L; Wong, Tien Y

2015-12-01

To determine the prevalence and risk factors of undiagnosed diabetic retinopathy (DR), in particular vision-threatening DR (VTDR) in a multiethnic Asian cohort. A population-based survey of 3353 Chinese, 3280 Malays and 3400 Indians (73.6% response) aged 40-80 years residing in Singapore. Diabetes mellitus (DM) was defined as random glucose ≥11.1 mmol/L, use of diabetic medication or a previous physician diagnosis. DR severity was graded from retinal photographs following the modified Airlie House classification. VTDR was defined as the presence of severe non-proliferative DR (NPDR), proliferative DR (PDR) or clinically significant macular oedema (CSMO), using the Eye Diseases Prevalence Research Group definition. Participants were deemed 'undiagnosed' if they reported no prior physician diagnosis in structured interviews, in those with the condition. Of 10 033 participants, 2376 had DM (23.7%), of which 805 (33.9%) had DR. Among 2376 with DM, 11.1% (n=263) were undiagnosed. Among 805 with DR, 671 (83.3%) were undiagnosed. Among 212 with VTDR, 59 (27.3%) were undiagnosed. In multivariate models, factors associated with undiagnosed VTDR were higher low-density lipoprotein (LDL) cholesterol (OR=1.53, 95% CI 0.99 to 2.35, p=0.05) and absence of visual impairment or blindness in any eye in terms of best-corrected vision OR=3.00, 95% CI 1.47 to 6.11, p=0.003). In this community, a quarter with VTDR is undiagnosed, and 8 in 10 with any DR are undiagnosed, compared with only 1 in 10 with DM undiagnosed. These findings suggest that screening for diabetes is successful, while screening for DR is currently inadequate in our population. Public health strategies to aid early diagnosis of DR in Singapore are urgently warranted to reduce blindness due to diabetes. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Educational Epistemology, Culture and History: Response to Joan Walton

ERIC Educational Resources Information Center

Inoue, Noriyuki

2016-01-01

In this response paper to Joan Walton's commentary on his article "The Role of Subjectivity in Teacher Expertise Development: Mindfully Embracing the 'Black Sheep' of Educational Research", Inoue acknowledges reading Dr. Walton's response to his paper with great interest and her discussion is a good follow up to the issues that he raised…

Differential Response: Response to Hughes and Colleagues

ERIC Educational Resources Information Center

Samuels, Bryan; Brown, Brett Vaughn

2013-01-01

In their critique of differential response (DR), Hughes and colleagues raise a number of important issues that are central to broader efforts at the Administration on Children, Youth, and Families (ACYF) including the need for greater reliance on evidence-based practice in child welfare, more rigorous evaluation methodologies, and a robust set of…

The influence of repressor DNA binding site architecture on transcriptional control.

PubMed

Park, Dan M; Kiley, Patricia J

2014-08-26

How the architecture of DNA binding sites dictates the extent of repression of promoters is not well understood. Here, we addressed the importance of the number and information content of the three direct repeats (DRs) in the binding and repression of the icdA promoter by the phosphorylated form of the global Escherichia coli repressor ArcA (ArcA-P). We show that decreasing the information content of the two sites with the highest information (DR1 and DR2) eliminated ArcA binding to all three DRs and ArcA repression of icdA. Unexpectedly, we also found that DR3 occupancy functions principally in repression, since mutation of this low-information-content site both eliminated DNA binding to DR3 and significantly weakened icdA repression, despite the fact that binding to DR1 and DR2 was intact. In addition, increasing the information content of any one of the three DRs or addition of a fourth DR increased ArcA-dependent repression but perturbed signal-dependent regulation of repression. Thus, our data show that the information content and number of DR elements are critical architectural features for maintaining a balance between high-affinity binding and signal-dependent regulation of icdA promoter function in response to changes in ArcA-P levels. Optimization of such architectural features may be a common strategy to either dampen or enhance the sensitivity of DNA binding among the members of the large OmpR/PhoB family of regulators as well as other transcription factors. In Escherichia coli, the response regulator ArcA maintains homeostasis of redox carriers under O2-limiting conditions through a comprehensive repression of carbon oxidation pathways that require aerobic respiration to recycle redox carriers. Although a binding site architecture comprised of a variable number of sequence recognition elements has been identified within the promoter regions of ArcA-repressed operons, it is unclear how this variable architecture dictates transcriptional regulation. By dissecting the role of multiple sequence elements within the icdA promoter, we provide insight into the design principles that allow ArcA to repress transcription within diverse promoter contexts. Our data suggest that the arrangement of recognition elements is tailored to achieve sufficient repression of a given promoter while maintaining appropriate signal-dependent regulation of repression, providing insight into how diverse binding site architectures link changes in O2 with the fine-tuning of carbon oxidation pathway levels. Copyright © 2014 Park and Kiley.

The Role of Subjectivity: Response to Noriyuki Inoue

ERIC Educational Resources Information Center

Walton, Joan

2016-01-01

This paper offers a response to Dr. Noriyuki Inoue's article published in this issue of the "International Journal for Transformative" research, entitled "The Role of Subjectivity in Teacher Expertise Development: Mindfully Embracing the 'Black Sheep' of Educational Research." Inoue freely uses the terms…

Envelope of Correlation Used with Deconvolution and Reconvolution to Remove the Direct Arrival in a Multipath Environment

DTIC Science & Technology

1990-03-01

London - Amsterdam:Geophysical Press, 1984. 3 Dicus, Ronald L., "Impulse response estimation with underwater explosive charge acoustic signals," Journal of... Ronald N. Bracewell, The Fourier Transform and Its Applications. New York: McGraw-Hill, 1978, pp 267-71. 6 Julius S. Bendat and Allan G. Pierson...Feuillade Code 212 Ted Kennedy L. Dolly Lee Code 240 Dr. Ron Wagstaff 833 Hancock Sq., Suite G Dr. Robert Farwell Bay St. Louis, MS 39520 Code 242 Roger

A Man-Portable Vector Sensor for Identification of Unexploded Ordnance

DTIC Science & Technology

2011-08-24

Hanover data of Section III-B2, and Dr. L. Pasion , J. Jacobson, and H. Ngo of Sky Research and Dr. L.-P. Song of the University of British Columbia for...of equivalent dipole polarizabilities in situ,” IEEE Trans. Geosci. Remote Sens., vol. 43, no. 7, pp. 1490–1498, Jul. 2005. [27] L. R. Pasion and D. W...P. Song, F. Shubitidze, L. R. Pasion , D. W. Oldenburg, and S. D. Billings, “Computing transient electromagnetic responses of a metallic object using

As Parents Go, So Go the Children. The Development and Adjustment of Children in the Military.

DTIC Science & Technology

1981-06-15

efforts are at least a beginning by the military to assume some responsibility in manag - ing the child abuse problems occurring within its ranks. Families ...the family (Allen, 1975). Treatment and prevention of child abuse and neglect in mili- tary families is promoted most effectively when it is managed ...and Management and Department of Psychology Dr. Larry Cummings College Park MD 20742 University of Wisconsin-Madison Graduate School of Business Dr. D

Report of the Defense Science Board Task Force on University Responsiveness to National Security Requirements.

DTIC Science & Technology

1982-01-01

R.ugustine Chairman iv OFFICE OF THE SECRETARY OF DEFENSE WASHINGTON, D.C. 20301 27 January 1982 DEFENSE SCIENCIE BOARD Mr. Norman R. Augustine Chai rman...Institute of Technology Dr. Norman Hackerman President Rice University Dr. Richard L. Haley Assistant Deputy Science and Technology USA Material ...Biological and Medical Sciences 51.8 67.8 22% Materials 53.2 65.1 13% Chemistry 47.8 60.1 17% Math and Computer Sciences 44.2 53.6 12% Oceanography 43.2

Proceedings of the NATO Radiological Human Response Subject Matter Expert Review Meeting, 26 June 2008, Albuquerque, New Mexico, United States of America

DTIC Science & Technology

2009-08-01

the proposed general casualty estimation process. The next two briefings described the technical details of the development and content of the...Forces Radiobiological Research Institute (AFRRI) Dr. Gene McClellan, Applied Research Associates (ARA) COL John Mercier, AFRRI Dr. Kyle Millage...marrow damage occurs; lethality ranges from LD50/60 to LD99/60; death occurs within 3.5 to 6 weeks with the radiation injury alone but is accelerated

A Study to Develop an Improved Organizational Structure for the Provision of Administrative Support for the Delivery of Health Care at Fitzsimons Army Medical Center

DTIC Science & Technology

1978-05-01

responsibility over their activities. The branch is comprised of an officer and a civilian clerk- steno - grapher. Major activities supervised include the...obtained during interviews with the following department chiefs: Colonel (Dr.) Nicholas C. Bethlenfalvay, MC, Department of Primary Care and Com- munity...January 1978. 121nterview with Colonel (Dr.) Nicholas C. Bethlenfalvay, MC, Chief, Department of Primary Care and Community Medicine, Fitzsimons Army

C3: The Compositional Construction of Context. A New, More Effective and Efficient Way to Marshal Inferences from Background Knowledge

DTIC Science & Technology

2014-09-01

quarter. Deep natural language understanding , efficient inference, pragmatics, background knowledge U U U SAR 4 Dr. David McDonald (781) 718-1964 C3...effective and efficient way to marshal inferences from background knowledge ’ N00014-13-1-0228 Dr. David McDonald Smart Information Flow Technologies, dba...for this collection of information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data

Electrocoagulation process to Chemical and Biological Oxygen Demand treatment from carwash grey water in Ahvaz megacity, Iran.

PubMed

Mohammadi, Mohammad Javad; Takdastan, Afshin; Jorfi, Sahand; Neisi, Abdolkazem; Farhadi, Majid; Yari, Ahmad Reza; Dobaradaran, Sina; Khaniabadi, Yusef Omidi

2017-04-01

In this work, we present the result of an electric coagulation process with iron and aluminum electrodes for removal of chemical and biological oxygen demand (COD and BOD) from grey water in different car washes of Ahvaz, Iran. Nowadays, one of the important dangerous that can contaminate water resources for drinking, agriculture and industrial is Car wash effluent [1,2]. In this study, initial COD and BOD concentration, pH of the solution, voltage power and reaction time was investigated. The concentration level of remaining COD and BOD in samples was measured, using DR/5000 UV-vis HACH spectrophotometer [3,4]. The effects of contact time, initial pH, electrical potential and voltage data on removal of COD and BOD were presented. Statistical analysis of the data was carried out using Special Package for Social Sciences (SPSS 16).

TRAIL overexpression co-regulated by Egr1 and HRE enhances radiosensitivity of hypoxic A549 cells depending on its apoptosis inducing role.

PubMed

Yang, Yan-Ming; Fang, Fang; Li, Xin; Yu, Lei; Wang, Zhi-Cheng

2017-01-01

Ionizing radiation can upregulate the expression levels of TRAIL and enhance tumor cell apoptosis. While Early growth response 1 (Egr1) gene promoter has radiation inducible characteristics, the expression for exogenous gene controlled by Egr1 promoter could be enhanced by ionizing radiation, but its efficiency is limited by tissue hypoxia. Hypoxia response elements (HREs) are important hypoxic response regulatory sequences and sensitivity enhancers. Therefore, we chose TRAIL as the gene radiotherapy to observe whether it is regulated by Egr1 and HER and its effects on A549 cells and its mechanism. The pcDNA3.1-Egr1-TRAIL (pc-E-hsT) and pcDNA3.1-HRE/Egr1-TRAIL (pc-H/E-hsT) plasmids containing Egr1-hsTRAIL and HRE/Egr1-hsTRAIL were transfected into A549 cells, the cells were treated by hypoxia and radiation. The TRAIL mRNA in the cells and protein concentration in the culture supernatants were measured by RT-PCR and ELISA, respectively. Mean lethal dose D0 value was evaluated with colony forming assay. The cell apoptotic rates were analyzed by FCM and TUNEL assay. Expression of DR4, DR5 and cleaved caspase-3 proteins were analyzed by western blotting. It showed that TRAIL mRNA expression and TRAIL concentration all significantly increased under hypoxia and/or radiation. D0 value of pc-H/E‑hsT transfected cells under hypoxia was lowest, indicating more high radiosensitivity. Hypoxia could not cause the pc-E-hsT transfected cell apoptotic rate increase, but there were promoting effects in pc-H/E-hsT transfected cells. DR4 had not obvious change in pc-E-hsT and pc-H/E-hsT transfected cells under normoxic and hypoxic condition, otherwise, DR5 and cleaved caspase-3 increased mostly in pc-H/E-hsT transfected cells under hypoxic condition. TRAIL overexpression was co-regulated by Egr1 and HRE. TRAIL might promote hypoxic A549 cell radiosensitivity and induce apoptosis depending on DR5 to caspase-3 pathways.

Effects of low and standard intra-abdominal pressure on systemic inflammation and immune response in laparoscopic adrenalectomy: A prospective randomised study.

PubMed

Schietroma, Mario; Pessia, Beatrice; Stifini, Derna; Lancione, Laura; Carlei, Francesco; Cecilia, Emanuela Marina; Amicucci, Gianfranco

2016-01-01

The advantages of laparoscopic adrenalectomy (LA) over open adrenalectomy are undeniable. Nevertheless, carbon dioxide (CO2) pneumoperitoneum may have an unfavourable effect on the local immune response. The aim of this study was to compare changes in the systemic inflammation and immune response in the early post-operative (p.o.) period after LA performed with standard and low-pressure CO2 pneumoperitoneum. We studied, in a prospective randomised study, 51 patients consecutively with documented adrenal lesion who had undergone a LA: 26 using standard-pressure (12-14 mmHg) and 25 using low-pressure (6-8 mmHg) pneumoperitoneum. White blood cells (WBC), peripheral lymphocyte subpopulation, human leucocyte antigen-DR (HLA-DR), neutrophil elastase, interleukin (IL)-6 and IL-1, and C-reactive protein (CRP) were investigated. Significantly higher concentrations of neutrophil elastase, IL-6 and IL-1 and CRP were detected p.o. in the standard-pressure group of patients in comparison with the low-pressure group (P < 0.05). A statistically significant change in HLA-DR expression was recorded p.o. at 24 h, as a reduction of this antigen expressed on the monocyte surface in patients from the standard group; no changes were noted in low-pressure group patients (P < 0.05). This study demonstrated that reducing the pressure of the pneumoperitoneum to 6-8 mmHg during LA reduced p.o. inflammatory response and averted p.o. immunosuppression.

Twenty years of Medicare and Medicaid: Covered populations, use of benefits, and program expenditures

PubMed Central

Gornick, Marian; Greenberg, Jay N.; Eggers, Paul W.; Dobson, Allen

1985-01-01

Marian Gornick is Director, Division of Beneficiary Studies, in the Office of Research, Health Care Financing Administration. She has been involved in research studies relating to Medicare and Medicaid since the programs were first implemented. Jay N. Greenberg is on the faculty of the Heller Graduate School, Brandeis University. Dr. Greenberg serves as the Associate Director for Research of the school's Health Policy Center. Paul W. Eggers is Chief, Program Evaluation Branch, in the Office of Research, Health Care Financing Administration (HCFA). Dr. Eggers’ research activities involve the evaluation of the impact of HCFA programs on the beneficiaries. Allen Dobson is Director, Office of Research, Health Care Financing Administration. Dr. Dobson is responsible for directing the planning and development of the Agency's research agenda. PMID:10311371

[Agustín Moreno: scientific psychology and women's legal responsibility in Spain].

PubMed

Bandrés, Javier; Llavona, Rafael

2011-11-01

Agustín Moreno Rodríguez (1886-1967) studied Medicine and Natural Sciences at the Central University of Spain, in Madrid. He was a student of Dr. Luis Simarro, the University's professor of Experimental Psychology and of Tomas Maestre, the University's professor of Medical Law, Toxicology and Psychiatry. In 1910, he published the text The woman's civil and penal responsibility during the menstrual period. In this work, he approaches the question of the legal responsibility of women, based on the principle of excitation/reaction of Claude Bernard and on his personal version of the concept of iteration elaborated by Luis Simarro. Dr. Moreno also defends the thesis that menstruation adds some uniqueness to the function of the feminine psyche and, therefore, modifies the responsibility of a woman's actions. We also comment on the predominant approach to the mind of women in the Spanish scientific psychology of that time and the reaction of the Spanish feminist intellectuals.

Three essays on the incentive structure of energy conservation programs

NASA Astrophysics Data System (ADS)

Okwelum, Edson Ogochukwu

This dissertation is comprised of three related essays examining the potential effectiveness of government energy efficiency programs from both the producer and consumer perspectives. The first chapter is based on a paper I coauthored with Corey Lang. In this manuscript, I address the question of whether strategic behavior by consumers could result in the erosion of energy savings in a demand response program. Understanding how the strategic behavior of consumers affects the net benefits from a demand response program has policy implications because of the increasing importance that demand response has come to play in utility load and reliability management during peak times. Using data from a large field experiment in California in 2007, we test the hypothesis that under a technology program, consumers' strategic behavior results in outcomes that are opposite what is obtainable under a program with price incentive or based of behavior. Chapter II is also an empirical study which explores how the preferences of consumers for large and heavy vehicles imposes costs on society in the form of external costs of accident. This chapter looks at how fleet changes in weight distribution due to corporate average fuel economy and consumer demand for heavier vehicles results in fatalities. It is important to understand how consumer behavior affects the accident rates so that one can obtain unbiased estimates of accident costs that go into benefit-cost analysis of the impact of regulations in automobiles. Chapter three addresses how unobserved heterogeneity and sorting affect the estimates of the consumer willingness to pay for reduction in future gasoline costs. This tradeoff is important to policy makers and manufactures because it could help explain why manufacturers fail to adopt technologies for which the fuel savings far outweigh the costs. The remainder of the abstract provides a more detailed outlines of the three essays. Chapter 1 explores strategic behavior by consumers in demand response programs. The chapter looks at how the confluences of consumer strategic behavior, technology and price incentives in demand response lead to conflicting outcomes. Demand response has become an important tool for utilities to manage load during peak periods. While the effects of demand response programs on peak load reductions are well studied and intuitive, assessments typically fail to recognize the potential for off-peak behavioral responses that may mitigate the total benefits of the program. Using smart meter consumption data on residential air conditioning units enrolled in a direct load control program, this paper examines changes in consumption prior to and after curtailment events. The manuscript rigorously estimates both peak and off peak changes in consumption to better understand net benefits of DR programs. We examine Pacific Gas and Electric's (PG&E) SmartAC program, which is designed to reduce peak cooling load by directly controlling air conditioning units of participants. Usually, program evaluation uses the availability of a control group to obtain unbiased estimates of program impacts. However, we do not have the luxury of a control group in our data. Instead we estimate unit-specific non-linear consumption models and then compare load on event days to predicted load. Importantly, we use data from the summer 2007 training period from a stratified random sample of 294 participating AC units. In contrast to subsequent summers and normal DR designs, during the training period curtailment days were called for many different temperature levels, not just the hottest days. This aspect means we are not predicting out of sample, and we can have greater confidence in our econometric evidence. Our methodology is validated by a falsification test in which we find no changes in consumption during peak or off-peak times on non-curtailment days that match the temperature and timing profile of actual curtailment days. Several key results emerge from this analysis. First, we confirm that the SmartAC program, like other DR and DLC programs, reduces peak load during event days. In this case, peak consumption was reduced 19% on average. However, we also find substantial increases in consumption in the hours preceding and the hours following an event by 8% and 7% respectively. Essentially, load is being displaced from peak to off-peak times. These behavioral changes mitigate the monetary benefits of the program by 41%. Chapter II addresses the question of how much accident risks would change if consumers who purchase larger, heavier vehicles of the existing fleet where to behave strategically given regulatory constraints imposed by corporate average fuel economy. The paper estimates both the risk of dying given a crash and the crash frequencies of different vehicles in the fleet. We use a unique data set that combines data from fatality analysis reporting system (FARS) and NASS General Estimates Systems. The estimation strategy used corrects for selection bias due to moral hazard problems. The two equations are estimated simultaneously using simulated maximum likelihood without the need for exclusion restrictions (Green 2003, 2007). This approach allows us to obtain estimates that are causal. One of the main issues that have been left unanswered in earlier works is the existence of Peltzman-type moral hazard problems and endogeneity of vehicle choice. In the presence of Peltzman-type moral hazard problems, drivers in heavier vehicles will find it advantageous to change their behavior in ways that have opposite effect to regulations. From a public policy perspective if increasing the weight of a vehicle increases the probability of its being involved in collisions, then we might be interested in more than the impact of heavier vehicles conditional on a crash occurring. We find that increasing the weight of any vehicle increases the probability of it being the heavier vehicle in a collision and the probability of it being involved in a fatal accident. The external costs translate to about 38 cents/gallon of gasoline. Chapter III explores how individual unobserved heterogeneity in tastes could lead to different customers sorting into different classes of fuel efficient vehicles and therefore affect estimates of consumer's ability to tradeoff vehicle costs and discounted future gasoline costs. The research question is important for several reasons. First, it is interesting from a theoretical basis if consumers make this trade off optimally. Many theoretical models in economics make the fundamental assumption that consumers equally weigh current and future events when making decisions today. However, plenty empirical and laboratory evidence conclude the contrary. Second, Regulatory Impact Analyses (RIA) of regulations on energy efficiency standards usually find that the benefits of these programs are in many times larger than the costs, with the fuel savings over the life of the vehicle accounting for the majority of the benefits. However, if fuel savings are large relative to costs, then the question is why are manufacturers not incorporating these technologies in their product offerings? Therefore understanding energy paradox is critical for evaluating the standards and regulations so that policy makers can identify baseline for assessment in cost-benefit analyses. In this paper, we contribute to the literature on Energy Paradox in Fuel Economy by providing empirical evidence that unobserved consumer heterogeneity could result in different consumers sorting into different classes of fuel efficient cars which results in consumers undervaluing fuel economy. Unlike existing literature in this topic, this paper accounts for sorting bias due unobserved heterogeneity by using a random coefficient logit with error components (Train and Winston 2007). We pair the random coefficient discrete choice model with a supply side model in which firms compete in Bertrand Nash fashion where price depends on elasticity of demand and marginal costs. With the random utility model, we can allow taste to vary across consumers. We treat the discounted operating costs and vehicle costs as random variables. We find that a substantial portion of upper the 95% of households in our sample correctly value fuel economy (61%) as they are willing to pay 0.99 to reduce obtain a 1.00 discounted future gasoline costs over the lifetime of the vehicle. And 29% of the upper 95% overvalue fuel economy as they are willing to pay $1.57. These results are in contrast to those reported elsewhere by Alcott and Wozny (2009) but support results from the simulation study by Bento et al 2012 who find that not accounting for sorting bias and consumer heterogeneity could lead to a conclusion that consumers undervalue fuel economy.

75 FR 15362 - Demand Response Compensation in Organized Wholesale Energy Markets

Federal Register 2010, 2011, 2012, 2013, 2014

2010-03-29

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission 18 CFR Part 35 [Docket No. RM10-17-000... FERC ] 61,213, PJM Interconnection, LLC, Docket No. EL09-68-000 Notice of Proposed Rulemaking Table of... Emergency Demand Response; NYISO's Emergency Demand Response Program; PJM's Emergency Load Response; and ISO...

Providing Reliability Services through Demand Response: A Prelimnary Evaluation of the Demand Response Capabilities of Alcoa Inc.

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

Starke, Michael R; Kirby, Brendan J; Kueck, John D

2009-02-01

Demand response is the largest underutilized reliability resource in North America. Historic demand response programs have focused on reducing overall electricity consumption (increasing efficiency) and shaving peaks but have not typically been used for immediate reliability response. Many of these programs have been successful but demand response remains a limited resource. The Federal Energy Regulatory Commission (FERC) report, 'Assessment of Demand Response and Advanced Metering' (FERC 2006) found that only five percent of customers are on some form of demand response program. Collectively they represent an estimated 37,000 MW of response potential. These programs reduce overall energy consumption, lower greenmore » house gas emissions by allowing fossil fuel generators to operate at increased efficiency and reduce stress on the power system during periods of peak loading. As the country continues to restructure energy markets with sophisticated marginal cost models that attempt to minimize total energy costs, the ability of demand response to create meaningful shifts in the supply and demand equations is critical to creating a sustainable and balanced economic response to energy issues. Restructured energy market prices are set by the cost of the next incremental unit of energy, so that as additional generation is brought into the market, the cost for the entire market increases. The benefit of demand response is that it reduces overall demand and shifts the entire market to a lower pricing level. This can be very effective in mitigating price volatility or scarcity pricing as the power system responds to changing demand schedules, loss of large generators, or loss of transmission. As a global producer of alumina, primary aluminum, and fabricated aluminum products, Alcoa Inc., has the capability to provide demand response services through its manufacturing facilities and uniquely through its aluminum smelting facilities. For a typical aluminum smelter, electric power accounts for 30% to 40% of the factory cost of producing primary aluminum. In the continental United States, Alcoa Inc. currently owns and/or operates ten aluminum smelters and many associated fabricating facilities with a combined average load of over 2,600 MW. This presents Alcoa Inc. with a significant opportunity to respond in areas where economic opportunities exist to help mitigate rising energy costs by supplying demand response services into the energy system. This report is organized into seven chapters. The first chapter is the introduction and discusses the intention of this report. The second chapter contains the background. In this chapter, topics include: the motivation for Alcoa to provide demand response; ancillary service definitions; the basics behind aluminum smelting; and a discussion of suggested ancillary services that would be particularly useful for Alcoa to supply. Chapter 3 is concerned with the independent system operator, the Midwest ISO. Here the discussion examines the evolving Midwest ISO market structure including specific definitions, requirements, and necessary components to provide ancillary services. This section is followed by information concerning the Midwest ISO's classifications of demand response parties. Chapter 4 investigates the available opportunities at Alcoa's Warrick facility. Chapter 5 involves an in-depth discussion of the regulation service that Alcoa's Warrick facility can provide and the current interactions with Midwest ISO. Chapter 6 reviews future plans and expectations for Alcoa providing ancillary services into the market. Last, chapter 7, details the conclusion and recommendations of this paper.« less

Synergistic Inhibition of Delayed Rectifier K+ and Voltage-Gated Na+ Currents by Artemisinin in Pituitary Tumor (GH3) Cells.

PubMed

So, Edmund Cheung; Wu, Sheng-Nan; Wu, Ping-Ching; Chen, Hui-Zhen; Yang, Chia-Jung

2017-01-01

Artemisinin (ART) is an anti-malarial agent reported to influence endocrine function. Effects of ART on ionic currents and action potentials (APs) in pituitary tumor (GH3) cells were evaluated by patch clamp techniques. ART inhibited the amplitude of delayed-rectifier K+ current (IK(DR)) in response to membrane depolarization and accelerated the process of current inactivation. It exerted an inhibitory effect on IK(DR) with an IC50 value of 11.2 µM and enhanced IK(DR) inactivation with a KD value of 14.7 µM. The steady-state inactivation curve of IK(DR) was shifted to hyperpolarization by 10 mV. Pretreatment of chlorotoxin (1 µM) or iloprost (100 nM) did not alter the magnitude of ART-induced inhibition of IK(DR) in GH3 cells. ART also decreased the peak amplitude of voltage-gated Na+ current (INa) with a concentration-dependent slowing in inactivation rate. Application of KMUP-1, an inhibitor of late INa, was effective at reversing ART-induced prolongation in inactivation time constant of INa. Under current-clamp recordings, ART alone reduced the amplitude of APs and prolonged the duration of APs. Under ART exposure, the inhibitory actions on both IK(DR) and INa could be a potential mechanisms through which this drug influences membrane excitability of endocrine or neuroendocrine cells appearing in vivo. © 2017 The Author(s). Published by S. Karger AG, Basel.

Lacking prognostic significance of beta 2-microglobulin, MHC class I and class II antigen expression in breast carcinomas.

PubMed Central

Wintzer, H. O.; Benzing, M.; von Kleist, S.

1990-01-01

To evaluate the impact of MHC antigen expression on the survival of patients with cancer, 77 human breast carcinomas were investigated for the expression of beta 2-microglobulin (beta 2m), HLA-A,B,C and HLA-DR. Thirty-one benign breast tumours were stained for comparison. The results for the carcinomas were related to the survival data of the cancer patients. The expression of beta 2m, HLA-A,B,C and HLA-DR was significantly lower in malignant tumours compared to the benign lesions. Whereas all benign tumours were positive for beta 2m and HLA-A,B,C and 28/31 positive for HLA-DR the following positivity rates were found in carcinomas: 74/77 for beta 2m, 57/77 for HLA-A,B,C and 10/77 for HLA-DR. The follow-up (median 45 months) of 66 cancer patients for overall survival and of 65 patients for disease-free survival revealed no influence of beta 2m, HLA-A,B,C or HLA-DR expression on the prognosis of this cancer. In conclusion, experimental data indicating the importance of MHC antigens in anti-tumour responses are not confirmed by the analysis of cancer patient survival data. Images Figure 1 Figure 2 Figure 3 Figure 4 PMID:2201398

Dr. Robert H. Goddard

NASA Image and Video Library

2010-01-04

Dr. Robert Hutchings Goddard (1882-1945). Dr. Goddard has been recognized as the father of American rocketry and as one of the pioneers in the theoretical exploration of space. Robert Hutchings Goddard, born in Worcester, Massachusetts, on October 5, 1882, was theoretical scientist as well as a practical engineer. His dream was the conquest of the upper atmosphere and ultimately space through the use of rocket propulsion. Dr. Goddard, died in 1945, but was probably as responsible for the dawning of the Space Age as the Wrights were for the beginning of the Air Age. Yet his work attracted little serious attention during his lifetime. However, when the United States began to prepare for the conquest of space in the 1950's, American rocket scientists began to recognize the debt owed to the New England professor. They discovered that it was virtually impossible to construct a rocket or launch a satellite without acknowledging the work of Dr. Goddard. More than 200 patents, many of which were issued after his death, covered this great legacy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Join us on Facebook

Dr. Robert Goddard

NASA Image and Video Library

2010-01-04

Dr. Robert Hutchings Goddard (1882-1945). Dr. Goddard has been recognized as the father of American rocketry and as one of the pioneers in the theoretical exploration of space. Robert Hutchings Goddard, born in Worcester, Massachusetts, on October 5, 1882, was theoretical scientist as well as a practical engineer. His dream was the conquest of the upper atmosphere and ultimately space through the use of rocket propulsion. Dr. Goddard, died in 1945, but was probably as responsible for the dawning of the Space Age as the Wrights were for the beginning of the Air Age. Yet his work attracted little serious attention during his lifetime. However, when the United States began to prepare for the conquest of space in the 1950's, American rocket scientists began to recognize the debt owed to the New England professor. They discovered that it was virtually impossible to construct a rocket or launch a satellite without acknowledging the work of Dr. Goddard. More than 200 patents, many of which were issued after his death, covered this great legacy. NASA Goddard Space Flight Center enables NASA’s mission through four scientific endeavors: Earth Science, Heliophysics, Solar System Exploration, and Astrophysics. Goddard plays a leading role in NASA’s accomplishments by contributing compelling scientific knowledge to advance the Agency’s mission. Follow us on Twitter Join us on Facebook

Expression and function of dopamine receptors in the developing medial frontal cortex and striatum of the rat

PubMed Central

Sillivan, Stephanie E.; Konradi, Christine

2011-01-01

The timeline of dopamine (DA) system maturation and the signaling properties of dopamine receptors (DRs) during rat brain development are not fully characterized. We used in situ hybridization and quantitative PCR to map DR mRNA transcripts in the medial frontal cortex (mFC) and striatum (STR) of the rat from embryonic day (E) 15 to E21. The developmental trajectory of DR mRNAs revealed distinct patterns of DA receptors 1 and 2 (DRD1, DRD2) in these brain regions. Whereas the mFC had a steeper increase in DRD1 mRNA, the STR had a steeper increase in DRD2 mRNA. Both DR mRNAs were expressed at a higher level in the STR compared to the mFC. To identify the functional properties of DRs during embryonic development, the phosphorylation states of cyclic AMP response element binding protein (CREB), extracellular signal-regulated kinase 1/2 (ERK1/2), and glycogen synthase kinase 3 beta (GSK3β) were examined after DR stimulation in primary neuronal cultures obtained from E15 and E18 embryos and cultured for 3 days to ensure a stable baseline level. DR-mediated signaling cascades were functional in E15 cultures in both brain regions. Because DA fibers do not reach the mFC by E15, and DA was not present in cultures, these data indicate that DRs can become functional in the absence of DA innervation. Since activation of DR signal transduction pathways can affect network organization of the developing brain, maternal exposure to drugs that affect DR activity may be liable to interfere with fetal brain development. PMID:22015925

Rapid Assessment of Avoidable Blindness and Diabetic Retinopathy in Gilan Province, Iran.

PubMed

Katibeh, Marzieh; Behboudi, Hassan; Moradian, Siamak; Alizadeh, Yousef; Beiranvand, Ramin; Sabbaghi, Hamideh; Ahmadieh, Hamid

2017-12-01

To conduct an assessment of avoidable blindness and diabetic retinopathy (DR) in Gilan, 2014. A cross-sectional population-based survey was performed on a representative sample of urban and rural individuals aged ≥50 years of the province. Blindness was defined as presenting visual acuity (PVA) <3/60 in the better eye. Moderate visual impairment (MVI) and severe visual impairment (SVI) were defined as 6/60 ≤ PVA <6/18 and 3/60 ≤ PVA <6/60 in the better eye, respectively. Diabetes mellitus (DM) was determined based on random blood sugar (RBS) levels ≥200 mg/dL or a previous diagnosis. We used the Scottish grading system to grade DR. We invited 2975 individuals from 85 clusters. Age- and sex-adjusted prevalence and 95% confidence interval (CI) of blindness, SVI, MVI, and DM in 2587 participants (response rate: 86.9%) were 1.5% (95% CI: 1.1-2.0), 1.5% (95% CI: 0.9-2.0), 11.3% (95% CI: 9.9-12.7) and 21.4% (95% CI: 19.2-23.7), respectively. The leading causes of blindness were cataract (47.1%), age-related macular degeneration (14.7%) and DR (8.8%). Cataract surgery (CS) coverage was 69.3%. The main challenges for CS were cost and unawareness. The outcome of CS was good in 66.9% of operated eyes. Any DR and/or maculopathy were observed in 25.3% (95% CI: 21.0-29.5) of subjects including 12.6% (95% CI: 9.7-15.6) sight-threatening DR. In previously known DM cases, 215 (41.7%) had never undergone an eye examination for DR. The proportion of avoidable blindness and DR is considerable in Gilan Province.

Demand Response and Energy Storage Integration Study

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

Ma, Ookie; Cheung, Kerry; Olsen, Daniel J.

2016-03-01

Demand response and energy storage resources present potentially important sources of bulk power system services that can aid in integrating variable renewable generation. While renewable integration studies have evaluated many of the challenges associated with deploying large amounts of variable wind and solar generation technologies, integration analyses have not yet fully incorporated demand response and energy storage resources. This report represents an initial effort in analyzing the potential integration value of demand response and energy storage, focusing on the western United States. It evaluates two major aspects of increased deployment of demand response and energy storage: (1) Their operational valuemore » in providing bulk power system services and (2) Market and regulatory issues, including potential barriers to deployment.« less

Demand Response and Energy Storage Integration Study

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

Ma, Ookie; Cheung, Kerry

Demand response and energy storage resources present potentially important sources of bulk power system services that can aid in integrating variable renewable generation. While renewable integration studies have evaluated many of the challenges associated with deploying large amounts of variable wind and solar generation technologies, integration analyses have not yet fully incorporated demand response and energy storage resources. This report represents an initial effort in analyzing the potential integration value of demand response and energy storage, focusing on the western United States. It evaluates two major aspects of increased deployment of demand response and energy storage: (1) Their operational valuemore » in providing bulk power system services and (2) Market and regulatory issues, including potential barriers to deployment.« less

Spatial discontinuity and temporal evolution of channel morphology along a mixed bedrock-alluvial river, upper Drôme River, southeast France: Contingent responses to external and internal controls

NASA Astrophysics Data System (ADS)

Toone, J.; Rice, S. P.; Piégay, H.

2014-01-01

The rehabilitation of degraded river channels is often guided by assumptions of continuity, yet in response to spatial and temporal variations in controlling conditions rivers typically display discontinuous response in space and time. This study examines the development of a 5 km reach of the Drôme River, S.E. France, characterised by alternating alluvial and bedrock zones that are separated by abrupt downstream transitions. This reach is representative of the Drôme River as a whole, and other rivers in the European Alps where braided channel planforms have been replaced by more complex, discontinuous morphologies. The primary aims are to understand how this spatial complexity has developed on the Drôme; evaluate how temporal channel changes have been affected by local factors, particularly bedrock exposures, and by long-term, catchment-scale changes in sediment supply and the flood activity; and consider the implications of this discontinuous geomorphology for reach management. The development of geomorphological zonation is examined by documenting sequential changes in channel planform between seven periods, using aerial photography (1948-2006) and by analysing change in bed elevation from profiles surveyed in 1928, 2003 and 2005. Between 1948 and 2001 bedrock exposed in the channel bed and along the floodplain margins defined discontinuities in sediment connectivity that were largely responsible for the configuration of channel zones. The impact of floods on this system was not proportional to flood magnitude. A modest flood in 1978 was an important event that, by incision and avulsion at key locations, defined a pattern of zonation that persisted until the end of the study in 2006. During the final 5 years of the study, alluvial zones that previously responded to large floods by widening underwent narrowing, despite the occurrence of a large flood, and led to an overall reduction in width variance. This resulted from progressive incision beneath and disconnection from formerly active channel areas, in response to long-term, catchment-scale reductions in sediment supply and flood frequency. In 2006 the pattern of zonation remains distinct, disguising this recent change in channel response and underlining the need for long-term and sequential perspectives of channel development to fully understand the processes in operation; contemporary snapshots of channel form may be misleading. Understanding interactions between inherent channel complexity and prevailing flow and sediment conditions, and how this shapes channel response to individual floods, is essential when interpreting future trajectories of channel change and likely response to management intervention.

Alveolar epithelial cells in idiopathic pulmonary fibrosis display upregulation of TRAIL, DR4 and DR5 expression with simultaneous preferential over-expression of pro-apoptotic marker p53.

PubMed

Akram, Khondoker M; Lomas, Nicola J; Forsyth, Nicholas R; Spiteri, Monica A

2014-01-01

Idiopathic pulmonary fibrosis (IPF) is a progressive, debilitating, and fatal lung disease of unknown aetiology with no current cure. The pathogenesis of IPF remains unclear but repeated alveolar epithelial cell (AEC) injuries and subsequent apoptosis are believed to be among the initiating/ongoing triggers. However, the precise mechanism of apoptotic induction is hitherto elusive. In this study, we investigated expression of a panel of pro-apoptotic and cell cycle regulatory proteins in 21 IPF and 19 control lung tissue samples. We reveal significant upregulation of the apoptosis-inducing ligand TRAIL and its cognate receptors DR4 and DR5 in AEC within active lesions of IPF lungs. This upregulation was accompanied by pro-apoptotic protein p53 overexpression. In contrast, myofibroblasts within the fibroblastic foci of IPF lungs exhibited high TRAIL, DR4 and DR5 expression but negligible p53 expression. Similarly, p53 expression was absent or negligible in IPF and control alveolar macrophages and lymphocytes. No significant differences in TRAIL expression were noted in these cell types between IPF and control lungs. However, DR4 and DR5 upregulation was detected in IPF alveolar macrophages and lymphocytes. The marker of cellular senescence p21(WAF1) was upregulated within affected AEC in IPF lungs. Cell cycle regulatory proteins Cyclin D1 and SOCS3 were significantly enhanced in AEC within the remodelled fibrotic areas of IPF lungs but expression was negligible in myofibroblasts. Taken together these findings suggest that, within the remodelled fibrotic areas of IPF, AEC can display markers associated with proliferation, senescence, and apoptotosis, where TRAIL could drive the apoptotic response. Clear understanding of disease processes and identification of therapeutic targets will direct us to develop effective therapies for IPF.

In Vitro and In Vivo Evaluation of 89Zr-DS-8273a as a Theranostic for Anti-Death Receptor 5 Therapy

PubMed Central

Burvenich, Ingrid J.G.; Lee, Fook-Thean; Guo, Nancy; Gan, Hui K.; Rigopoulos, Angela; Parslow, Adam C.; O'Keefe, Graeme J.; Gong, Sylvia J.; Tochon-Danguy, Henri; Rudd, Stacey E.; Donnelly, Paul S.; Kotsuma, Masakatsu; Ohtsuka, Toshiaki; Senaldi, Giorgio; Scott, Andrew M.

2016-01-01

Background: DS-8273a, an anti-human death receptor 5 (DR5) agonistic antibody, has cytotoxic activity against human cancer cells and induces apoptosis after specific binding to DR5. DS-8273a is currently being used in clinical Phase I trials. This study evaluated the molecular imaging of DR5 expression in vivo in mouse tumor models using SPECT/CT and PET/MRI, as a tool for drug development and trial design. Methods: DS-8273a was radiolabeled with indium-111 and zirconium-89. Radiochemical purity, immunoreactivity, antigen binding affinity and serum stability were assessed in vitro. In vivo biodistribution and pharmacokinetic studies were performed, including SPECT/CT and PET/MR imaging. A dose-escalation study using a PET/MR imaging quantitative analysis was also performed to determine DR5 receptor saturability in a mouse model. Results: 111In-CHX-A″-DTPA-DS-8273a and 89Zr-Df-Bz-NCS-DS-8273a showed high immunoreactivity (100%), high serum stability, and bound to DR5 expressing cells with high affinity (Ka, 1.02-1.22 × 1010 M-1). The number of antibodies bound per cell was 32,000. In vivo biodistribution studies showed high and specific uptake of 111In-CHX-A″-DTPA-DS-8273a and 89Zr-Df-Bz-NCS-DS-8273a in DR5 expressing COLO205 xenografts, with no specific uptake in normal tissues or in DR5-negative CT26 xenografts. DR5 receptor saturation was observed in vivo by biodistribution studies and quantitative PET/MRI analysis. Conclusion: 89Zr-Df-Bz-NCS-DS-8273a is a potential novel PET imaging reagent for human bioimaging trials, and can be used for effective dose assessment and patient response evaluation in clinical trials. PMID:27924159

GENESI-DR: Discovery, Access and on-Demand Processing in Federated Repositories

NASA Astrophysics Data System (ADS)

Cossu, Roberto; Pacini, Fabrizio; Parrini, Andrea; Santi, Eliana Li; Fusco, Luigi

2010-05-01

GENESI-DR (Ground European Network for Earth Science Interoperations - Digital Repositories) is a European Commission (EC)-funded project, kicked-off early 2008 lead by ESA; partners include Space Agencies (DLR, ASI, CNES), both space and no-space data providers such as ENEA (I), Infoterra (UK), K-SAT (N), NILU (N), JRC (EU) and industry as Elsag Datamat (I), CS (F) and TERRADUE (I). GENESI-DR intends to meet the challenge of facilitating "time to science" from different Earth Science disciplines in discovery, access and use (combining, integrating, processing, …) of historical and recent Earth-related data from space, airborne and in-situ sensors, which are archived in large distributed repositories. In fact, a common dedicated infrastructure such as the GENESI-DR one permits the Earth Science communities to derive objective information and to share knowledge in all environmental sensitive domains over a continuum of time and a variety of geographical scales so addressing urgent challenges such as Global Change. GENESI-DR federates data, information and knowledge for the management of our fragile planet in line with one of the major goals of the many international environmental programmes such as GMES, GEO/GEOSS. As of today, 12 different Digital Repositories hosting more than 60 heterogeneous dataset series are federated in GENESI-DR. Series include satellite data, in situ data, images acquired by airborne sensors, digital elevation models and model outputs. ESA has started providing access to: Category-1 data systematically available on Internet; level 3 data (e.g., GlobCover map, MERIS Global Vegetation Index); ASAR products available in ESA Virtual Archive and related to the Supersites initiatives. In all cases, existing data policies and security constraints are fully respected. GENESI-DR also gives access to Grid and Cloud computing resources allowing authorized users to run a number of different processing services on the available data. The GENESI-DR operational platform is currently being validated against several applications from different domains, such as: automatic orthorectification of SPOT data; SAR Interferometry; GlobModel results visualization and verification by comparison with satellite observations; ozone estimation from ERS-GOME products and comparison with in-situ LIDAR measures; access to ocean-related heterogeneous data and on-the-fly generated products. The project is adopting, ISO 19115, ISO 19139 and OGC standards for geospatial metadata discovery and processing, is compliant with the basis of INSPIRE Implementing Rules for Metadata and Discovery, and uses the OpenSearch protocol with Geo extensions for data and services discovery. OpenSearch is now considered by OGC a mass-market standard to provide machine accessible search interface to data repositories. GENESI-DR is gaining momentum in the Earth Science community thanks to the active participation to the GEO task force "Data Integration and Analysis Systems" and to the several collaborations with EC projects. It is now extending international cooperation agreements specifically with the NASA (Goddard Earth Sciences Data Information Services), with CEODE (the Center of Earth Observation for Digital Earth of Beijing), with the APN (Asia-Pacific Network), with University of Tokyo (Japanese GeoGrid and Data Integration and Analysis System).

Pupillary Response to Cognitive Demand in Parkinson’s Disease: A Pilot Study

PubMed Central

Kahya, Melike; Moon, Sanghee; Lyons, Kelly E.; Pahwa, Rajesh; Akinwuntan, Abiodun E.; Devos, Hannes

2018-01-01

Previous studies have shown that pupillary response, a physiological measure of cognitive workload, reflects cognitive demand in healthy younger and older adults. However, the relationship between cognitive workload and cognitive demand in Parkinson’s disease (PD) remains unclear. The aim of this pilot study was to examine the pupillary response to cognitive demand in a letter-number sequencing (LNS) task between 16 non-demented individuals with PD (age, median (Q1–Q3): 68 (62–72); 10 males) and 10 control participants (age: 63 (59–67); 2 males), matched for age, education, and Montreal Cognitive Assessment (MOCA) scores. A mixed model analysis was employed to investigate cognitive workload changes as a result of incremental cognitive demand for both groups. As expected, no differences were found in cognitive scores on the LNS between groups. Cognitive workload, exemplified by greater pupil dilation, increased with incremental cognitive demand in both groups (p = 0.003). No significant between-group (p = 0.23) or interaction effects were found (p = 0.45). In addition, individuals who achieved to complete the task at higher letter-number (LN) load responded differently to increased cognitive demand compared with those who completed at lower LN load (p < 0.001), regardless of disease status. Overall, the findings indicated that pupillary response reflects incremental cognitive demand in non-demented people with PD and healthy controls. Further research is needed to investigate the pupillary response to incremental cognitive demand of PD patients with dementia compared to non-demented PD and healthy controls. Highlights -Pupillary response reflects cognitive demand in both non-demented people with PD and healthy controls-Although not significant due to insufficient power, non-demented individuals with PD had increased cognitive workload compared to the healthy controls throughout the testing-Pupillary response may be a valid measure of cognitive demand in non-demented individuals with PD-In future, pupillary response might be used to detect cognitive impairment in individuals with PD PMID:29692720

[Countryside obstetrics--Dr. Franz von Ottenthal and the South Tyrolean Medical Market (1860-1869)].

PubMed

Hilber, Marina

2012-01-01

The paper focuses on the structure of the obstetric market in a rural region of alpine South Tyrol (today: Italy) throughout the 1860s. Besides midwives and parturient women, also male obstetricians are traceable in the actual research area of the Tauferer Ahrntal. Among them was the general practitioner Dr. Franz von Ottenthal, whose medical records (Historiae Morborum, 1847-1899) are used to reconstruct the participation of physicians in the obstetric market. Special emphasis lies on the evaluation of the predominant hierarchies (midwives/surgeons/physicians) and the position of Franz von Ottenthal in this specialized medical sub-segment. Therefore, the quantitative extent of obstetric intervention as well as the qualitative dimension of treatments (medication, surgeries) is investigated. So far, the relevance of Ottenthals obstetric practice as to the gender ratio has been measured as rather high, considering that he generally treated more female than male patients. An attempt will be made to estimate the significance of the obstetric segment within his practice in order to find an explanatory approach for the higher female medical demand.

Economics of Future Growth in Photovoltaics Manufacturing; NREL (National Renewable Energy Laboratory)

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

Basore, Paul; Chung, Donald; Buonassisi, Tonio

2015-06-14

The past decade’s record of growth in the photovoltaic manufacturing industry indicates that global investment in manufacturing capacity for photovoltaic modules tends to increase in proportion to the size of the industry. The slope of this proportionality determines how fast the industry will grow in the future. Two key parameters determine this slope. One is the annual global investment in manufacturing capacity normalized to the manufacturing capacity for the previous year (capacity-normalized capital investment rate, CapIR, units $/W). The other is how much capital investment is required for each watt of annual manufacturing capacity, normalized to the service life ofmore » the assets (capacity-normalized capital demand rate, CapDR, units $/W). If these two parameters remain unchanged from the values they have held for the past few years, global manufacturing capacity will peak in the next few years and then decline. However, it only takes a small improvement in CapIR to ensure future growth in photovoltaics. Any accompanying improvement in CapDR will accelerate that growth.« less

Comparison of conceptually based and regression rainfall-runoff models, Denver Metropolitan area, Colorado, and potential applications in urban areas

USGS Publications Warehouse

Lindner-Lunsford, J. B.; Ellis, S.R.

1987-01-01

Multievent, conceptually based models and a single-event, multiple linear-regression model for estimating storm-runoff quantity and quality from urban areas were calibrated and verified for four small (57 to 167 acres) basins in the Denver metropolitan area, Colorado. The basins represented different land-use types - light commercial, single-family housing, and multi-family housing. Both types of models were calibrated using the same data set for each basin. A comparison was made between the storm-runoff volume, peak flow, and storm-runoff loads of seven water quality constituents simulated by each of the models by use of identical verification data sets. The models studied were the U.S. Geological Survey 's Distributed Routing Rainfall-Runoff Model-Version II (DR3M-II) (a runoff-quantity model designed for urban areas), and a multievent urban runoff quality model (DR3M-QUAL). Water quality constituents modeled were chemical oxygen demand, total suspended solids, total nitrogen, total phosphorus, total lead, total manganese, and total zinc. (USGS)

Design, optimization and evaluation of a "smart" pixel sensor array for low-dose digital radiography

NASA Astrophysics Data System (ADS)

Wang, Kai; Liu, Xinghui; Ou, Hai; Chen, Jun

2016-04-01

Amorphous silicon (a-Si:H) thin-film transistors (TFTs) have been widely used to build flat-panel X-ray detectors for digital radiography (DR). As the demand for low-dose X-ray imaging grows, a detector with high signal-to-noise-ratio (SNR) pixel architecture emerges. "Smart" pixel is intended to use a dual-gate photosensitive TFT for sensing, storage, and switch. It differs from a conventional passive pixel sensor (PPS) and active pixel sensor (APS) in that all these three functions are combined into one device instead of three separate units in a pixel. Thus, it is expected to have high fill factor and high spatial resolution. In addition, it utilizes the amplification effect of the dual-gate photosensitive TFT to form a one-transistor APS that leads to a potentially high SNR. This paper addresses the design, optimization and evaluation of the smart pixel sensor and array for low-dose DR. We will design and optimize the smart pixel from the scintillator to TFT levels and validate it through optical and electrical simulation and experiments of a 4x4 sensor array.

A novel “humanized mouse” model for autoimmune hepatitis and the association of gut microbiota with liver inflammation

PubMed Central

Yuksel, Muhammed; Wang, Yipeng; Tai, Ningwen; Peng, Jian; Guo, Junhua; Beland, Kathie; Lapierre, Pascal; David, Chella; Alvarez, Fernando; Colle, Isabelle; Yan, Huiping; Mieli-Vergani, Giorgina; Vergani, Diego; Ma, Yun; Wen, Li

2016-01-01

Background Autoimmune hepatitis (AIH) in humans is a severe inflammatory liver disease, characterized by interface hepatitis, the presence of circulating autoantibodies and hyper-gammaglobulinemia. There are two types of AIH, type-1 (AIH-1) and type-2 (AIH-2) characterized by distinct autoimmune serology. Patients with AIH-1 are positive for anti-smooth muscle and/or anti-nuclear (SMA/ANA) autoantibodies whereas patients with AIH-2 have anti-liver kidney microsomal type 1 (anti-LKM1) and/or anti-liver cytosol type 1 (anti-LC1) autoantibodies. Cytochrome P4502D6 (CYP2D6) is the antigenic target of anti-LKM1 and formiminotransferase cyclodeaminase (FTCD) is the antigenic target of anti-LC1. It is known that AIH, both type-1 and type-2, is strongly linked to the Human Leukocyte Antigen (HLA) alleles -DR3, -DR4 and -DR7. However, the direct evidence of the association of HLA with AIH is lacking. Methods We developed a novel mouse model of AIH using the HLA-DR3 transgenic mouse on the non-obese diabetic (NOD) background (HLA-DR3 NOD) by immunization of HLA-DR3− and HLA-DR3+ NOD mice with a DNA plasmid, coding for human CYP2D6/FTCD fusion protein. Results Immunization with CYP2D6/FTCD leads to a sustained elevation of alanine aminotransferase (ALT), development of ANA and anti-LKM1/anti-LC1 autoantibodies, chronic immune cell infiltration and parenchymal fibrosis on liver histology in HLA-DR3+ mice. Immunized mice also showed an enhanced Th1 immune response and paucity of the frequency of regulatory T-cell (Treg) in the liver. Moreover, HLA-DR3+ mice with exacerbated AIH showed reduced diversity and total load of gut bacteria. Conclusion Our humanized animal model has provided a novel experimental tool to further elucidate the pathogenesis of AIH and to evaluate the efficacy and safety of immunoregulatory therapeutic interventions in vivo. PMID:26185095

National Defense Budget Estimates for FY 1990/1991

DTIC Science & Technology

1989-03-01

but have no effect on TOA. These are collections from the public that arise out of the business-type or market -oriented activities of the Government...magnitude and direction of changes in supply and demand in various markets . There are many different measures of inflation: a. GNP Implicit Price...m a Dmo 0 o~o 0 NCDC wm~ 0 CMI-r- CC40~ ’jU.", 101,0. >a% r- Ln -m I*CN Ln LA CO -4 M m 04 w-4 to 0 C Dr- CN c * -m oNLn -,r mm m -ddL -ia a o Nr, r

Responding to "Issues in Differential Response"

ERIC Educational Resources Information Center

Perry, Robin Ernest

2013-01-01

Hughes, Rycus, Saunders-Adams, Hughes, and Hughes's article represents an important effort to critically examine the foundation of thought and empirical evidence associated with the rise in prominence of differential response (DR) within child welfare systems throughout the United States. The insights and criticisms offered are an important…

76 FR 57717 - Endangered and Threatened Species; Take of Anadromous Fish

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-16

.... SUMMARY: NMFS has issued permit 15926 to UC Davis Department of Animal Science Genomic Variation Laboratory [Responsible Party: Dr. Bernie P. May], Department of Animal Science, University of California... [Responsible Party: Dave A. Vogel], P.O. Box 1210, Red Bluff, CA 96080; for purposes of scientific research...

The Quest for Relevant Air Power: Continental European Responses to the Air Power Challenges of the Post-Cold War Era

DTIC Science & Technology

2011-08-01

Air Power Centre]), Col (GS) Thomas Lorber, FüAk (Führungsakademie); Lt Col Dr. Wolfgang Schmidt, Military- Historical Research Office, Potsdam; Lt Gen...Col (GS) Dr. Michael Wolfgang Romba, Col (GS) Hans-Dieter Schön and his staff, Col (GS) Lothar Schmidt, and Lt Col (GS) Michael Trautermann. In the...Multinational Air Wing (DMAW) Project,” accessed 2 March 2007, http://www.euroairgroup.org/act_DMAW.htm. 75. Wolfgang Lange, “Lufttransport—Ansätze

Clarence Allen talks about the responsibilities in earthquake prediction

USGS Publications Warehouse

Spall, H.

1978-01-01

Dr. Clarence R. Allen is professor of geology and geophysics at the California Institute of Technology. He has been a member of advisory panels to the Executive Office of the President, National Academy of Sciences, National Science Foundation, U.S Geological Survey, UNESCO, California State Mining and Geology Board, and the California Department of Water Resources. Dr. Allen has been President of both the Geological Society of America and the Seismological Society of America (SSA). The title of this interview is based on his presidential address to the SSA in 1976. 

Epigenetic Mediation of Endocrine and Immune Response in an Animal Model of Gulf War Illness

DTIC Science & Technology

2015-10-01

Illness 5b. GRANT NUMBER W81XWH-14-1-0550 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Patrick O. McGowan, PhD, Gordon Broderick , PhD...ensure alignment with the overarching Consortium GW120045 (project W81XWH-12-2-0085; Morris, PI). Feb. 24-27 2015. Dr. Broderick met with Drs...Coordinated sharing of existing RNA sequencing data with McGowan group for first review of most promising target genes Mar. 30-31 2015. Dr. Broderick met

Report to Congress on the Activities of the DoD Office of Technology Transition

DTIC Science & Technology

2000-01-01

Form ApprovedOMB No. 0704-0188 Public reporting burden for the collection of information is estimated to average 1 hour per response, including the...development of military rations that look freshly prepared yet can be kept at room temperature for up to three years; • Dr. Mark Spano and Dr. Visarath In of...In the late 1990’s, an average of 1 million new people per year are certified or take introductory Scuba classes. If sales reach just 1% of new

Revisions to the PETROS 4 Shell Response Code.

DTIC Science & Technology

1984-02-01

change in the corresponding curvature tensor 𔃿’. DD(JLA) ftA cl &y()j * -. ,:"DD2(J,LA) DEL See ZETA 146,156 DELBAR 71 See ZETA 409 DELNOR See EQUIL2...Cleveland, OH 44135 1 AFML (LLN, Dr. Nicholas) 1 Bell Helicopter Textron Wright-Patterson AFB, OH 45433 ATTN: Mr. Nile Fischer P.O. Box 482 I ASD/ENFTV, Mr...2406A 1 Texas A&M University 1000 Western Avenue Dept Aerospace Eng West Lynn, MA 01905 ATTN: Dr. W. Haisler College Station, TX 77843 I Kaman Tempo

Loss of PTEN as a Predictive Biomarker of Response to Lithium Chloride, A Potential Targeted Treatment for Breast Cancer

DTIC Science & Technology

2013-11-01

COVERED (From - To) 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER...The grant was awarded on June 1st 2010. Dr. Higgins graduated from her Oncology Fellowship Program in Johns Hopkins Hospital on June 30th and... grant to support Dr. Higgins as she continued this work was submitted and processed in June 2010 in anticipation of this move. Johns Hopkins University

Gaia: Mapping the Milky Way: The Scientific Promise of Gaia DR2

NASA Astrophysics Data System (ADS)

Walton, Nicholas; ESA Gaia, Data Processing and Analysis Consortium (DPAC)

2018-06-01

The ESA Gaia mission will release its first major all sky astrometric catalogue (Gaia DR2), of more than 1.3 billion stars in our Galaxy, on 25 April 2018.This presentation will provide an overview of the Gaia mission, focussing on the significant scientific potential of the Gaia DR2 release. This is based on 22 months of input data and allows for a full Gaia stand alone astrometric solution, including parallaxes and proper motions, of over 1.3 billion sources. The astrometric uncertainties in Gaia DR2 will be at the level of tens of micro-arcsec for sources G<15.The Gaia DR2 release provides not only high precision full five parameter astrometry, but also a complete photometric catalogue of the sources on an all sky homogeneous photometric system in the Gaia G band and broad bands G_BP and G_RP. The release will include median radial velocities for more than six million stars (brighter that G_RVS = 12) together with a set of astrophysical parameters (including stellar temperatures) for some 150 million stars. Finally the Gaia DR2 release will include a set of additional data products including the light curves of more than half a million variable stars, and the positions of more than thirteen thousand objects in our Solar System.Together with the Gaia DR2 data products and associated release documentation, a small number of performance verification papers, using Gaia DR2 data only to provide new insights into a number of key areas of Gaia science, will be published in a special edition of A&A. These will provide demonstrations of the scientific potential of the Gaia DR2 catalogue, and also highlight some of the issues and limitations involved in the use of the Gaia DR2 data.The Gaia mission and Gaia Data Releases are made possible through the dedication and expertise of the community scientists and engineers involved in the design, construction, and operation of Gaia (led by ESA) and the collaboration of some 450 scientists and software engineers responsible for the complex task of analysing the processed data (the DPAC). The role of both will be covered in the presentation.The presentation will conclude with a brief look ahead to the longer term Gaia data release schedule.

Interoperability of Demand Response Resources Demonstration in NY

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

Wellington, Andre

2014-03-31

The Interoperability of Demand Response Resources Demonstration in NY (Interoperability Project) was awarded to Con Edison in 2009. The objective of the project was to develop and demonstrate methodologies to enhance the ability of customer sited Demand Response resources to integrate more effectively with electric delivery companies and regional transmission organizations.

Opportunities for Energy Efficiency and Open Automated Demand Response in Wastewater Treatment Facilities in California -- Phase I Report

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

Lekov, Alex; Thompson, Lisa; McKane, Aimee

This report summarizes the Lawrence Berkeley National Laboratory?s research to date in characterizing energy efficiency and automated demand response opportunities for wastewater treatment facilities in California. The report describes the characteristics of wastewater treatment facilities, the nature of the wastewater stream, energy use and demand, as well as details of the wastewater treatment process. It also discusses control systems and energy efficiency and automated demand response opportunities. In addition, several energy efficiency and load management case studies are provided for wastewater treatment facilities.This study shows that wastewater treatment facilities can be excellent candidates for open automated demand response and thatmore » facilities which have implemented energy efficiency measures and have centralized control systems are well-suited to shift or shed electrical loads in response to financial incentives, utility bill savings, and/or opportunities to enhance reliability of service. Control technologies installed for energy efficiency and load management purposes can often be adapted for automated demand response at little additional cost. These improved controls may prepare facilities to be more receptive to open automated demand response due to both increased confidence in the opportunities for controlling energy cost/use and access to the real-time data.« less

29 CFR 20.78 - Notifications.

Code of Federal Regulations, 2011 CFR

2011-07-01

... designee) of the creditor Labor Department agency shall send appropriate written demands to the debtor in... written demands at not more than 30-day intervals will normally be made unless a response to the first or second demand indicates that a further demand would be futile and the debtor's response does not require...

29 CFR 20.78 - Notifications.

Code of Federal Regulations, 2010 CFR

2010-07-01

... designee) of the creditor Labor Department agency shall send appropriate written demands to the debtor in... written demands at not more than 30-day intervals will normally be made unless a response to the first or second demand indicates that a further demand would be futile and the debtor's response does not require...

A Center for Advanced Electrical and Structural Polymers

DTIC Science & Technology

1988-10-31

REPORT I 3b. TIME COVERED 14. DATE OF REPORT (Year, Month, Oay) IS. PAGE COUNT Final j FROM TO 44 16. SUPPLEMENTARY NOTATION 17. COSATI CODES 18...Banhegyi Dr. N. Easwar Dr. Z. Chai Dr. K. Liang Dr. S. Choe Dr. G. Smyth Dr. P. Cifra Dr. J . Kim Dr. W. Huh Dr. Q. Bhatia Dr. J . Grobelny Dr. P... J . Chen (WSU) Dr. G. Quin Dr. M. Sinksy (WSU) Dr. N. Segudovic Dr. R. Miller (WSU) Dr. G. Shy Dr. Y. Gur Mr. L. Wu Dr. T. Bleha Dr. A. Sikora Dr. H

Joint Planning Of Energy Storage and Transmission Considering Wind-Storage Combined System and Demand Side Response

NASA Astrophysics Data System (ADS)

Huang, Y.; Liu, B. Z.; Wang, K. Y.; Ai, X.

2017-12-01

In response to the new requirements of the operation mode of wind-storage combined system and demand side response for transmission network planning, this paper presents a joint planning of energy storage and transmission considering wind-storage combined system and demand side response. Firstly, the charge-discharge strategy of energy storage system equipped at the outlet of wind farm and demand side response strategy are analysed to achieve the best comprehensive benefits through the coordination of the two. Secondly, in the general transmission network planning model with wind power, both energy storage cost and demand side response cost are added to the objective function. Not only energy storage operation constraints and but also demand side response constraints are introduced into the constraint condition. Based on the classical formulation of TEP, a new formulation is developed considering the simultaneous addition of the charge-discharge strategy of energy storage system equipped at the outlet of the wind farm and demand side response strategy, which belongs to a typical mixed integer linear programming model that can be solved by mature optimization software. The case study based on the Garver-6 bus system shows that the validity of the proposed model is verified by comparison with general transmission network planning model. Furthermore, the results demonstrate that the joint planning model can gain more economic benefits through setting up different cases.

Design for an aging brain.

PubMed

Thaler, David S

2002-01-01

Vaillancourt and Newell (Neurobiol. of Aging 2001) show that although many aging systems decrease in complexity as anticipated by Lipsitz and Goldberger (JAMA 1992), other aging systems increase in complexity. Vaillancourt and Newell explain the discrepancy by proposing that systems with a point attractor decrease in complexity with age, whereas those with an oscillating attractor increase in complexity with age. Vaillancourt and Newell are certainly correct that no one direction fits all results. Aging and death sometimes follow from a system being too simple, or, too complex. A perspective, based on the work of W. Ross Ashby (1956 and http://pespmc1.vub.ac.be/ASHBBOOK.html) is used in this commentary to consider why some systems become apparently more simple and others more complex as they age. In this Ashby-inspired view the measured complexity of a system's Responses to Disturbances is proportional to the ratio D/R, where D and R are sets containing the variety of possible disturbances and responses. The model expands on Ashby's by proposing that D consists of two components, Dp and Du. Dp consists of disturbances that are a function of the system's perception. Responses to Dp are often anticipatory and the response itself dominates the outcome. Du are disturbances that are unavoidable. Outcomes decrease or increase in measured entropy as a function of changes in (Dp + Du)/R. The variety of elements in both Dp and R decrease with age. When D/R decreases with age, the system shows less complexity. Conversely when D/R increases with Age, the results become more entropic.

Renewable Energy Resources Portfolio Optimization in the Presence of Demand Response

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

Behboodi, Sahand; Chassin, David P.; Crawford, Curran

In this paper we introduce a simple cost model of renewable integration and demand response that can be used to determine the optimal mix of generation and demand response resources. The model includes production cost, demand elasticity, uncertainty costs, capacity expansion costs, retirement and mothballing costs, and wind variability impacts to determine the hourly cost and revenue of electricity delivery. The model is tested on the 2024 planning case for British Columbia and we find that cost is minimized with about 31% renewable generation. We also find that demand responsive does not have a significant impact on cost at themore » hourly level. The results suggest that the optimal level of renewable resource is not sensitive to a carbon tax or demand elasticity, but it is highly sensitive to the renewable resource installation cost.« less

Ocular myasthenia gravis induced by human acetylcholine receptor ϵ subunit immunization in HLA DR3 transgenic mice.

PubMed

Wu, Xiaorong; Tuzun, Erdem; Saini, Shamsher S; Wang, Jun; Li, Jing; Aguilera-Aguirre, Leopoldo; Huda, Ruksana; Christadoss, Premkumar

2015-12-01

Extraocular muscles (EOM) are preferentially involved in myasthenia gravis (MG) and acetylcholine receptor (AChR) antibody positive MG patients may occasionally present with isolated ocular symptoms. Although experimental autoimmune myasthenia gravis (EAMG) induced by whole AChR immunization closely mimics clinical and immunopathological aspects of MG, EOM are usually not affected. We have previously developed an EAMG model, which imitates EOM symptoms of MG by immunization of human leukocyte antigen (HLA) transgenic mice with α or γ-subunits of human AChR (H-AChR). To investigate the significance of the ϵ-subunit in ocular MG, we immunized HLA-DR3 and HLA-DQ8 transgenic mice with recombinant H-AChR ϵ-subunit expressed in Escherichia coli. HLA-DR3 transgenic mice showed significantly higher clinical ocular and generalized MG severity scores and lower grip strength values than HLA-DQ8 mice. H-AChR ϵ-subunit-immunized HLA-DR3 transgenic mice had higher serum anti-AChR antibody (IgG, IgG1, IgG2b, IgG2c and IgM) levels, neuromuscular junction IgG and complement deposit percentages than ϵ-subunit-immunized HLA-DQ8 transgenic mice. Control mice immunized with E. coli extract or complete Freund adjuvant (CFA) did not show clinical and immunopathological features of ocular and generalized EAMG. Lymph node cells of ϵ-subunit-immunized HLA-DR3 mice showed significantly higher proliferative responses than those of ϵ-subunit-immunized HLA-DQ8 mice, crude E. coli extract-immunized and CFA-immunized transgenic mice. Our results indicate that the human AChR ϵ-subunit is capable of inducing myasthenic muscle weakness. Diversity of the autoimmune responses displayed by mice expressing different HLA class II molecules suggests that the interplay between HLA class II alleles and AChR subunits might have a profound impact on the clinical course of MG. Copyright © 2015 European Federation of Immunological Societies. Published by Elsevier B.V. All rights reserved.

You are my teachers.

PubMed

Edlich, Richard F

2005-01-01

Dr. Owen Wangensteen reminded Dr. Edlich that the chief responsibility of a teacher is to create an atmosphere friendly to learning. Dr Wangensteen indicated that the role of professor has been defined as that of teacher, clinician, and investigator. He then indicated that two more responsibilities must be added: (1) sideline cheerleader and (2) regimental water carrier. Above all those enumerated functions, he believed that the most important concern of a professor is to create an atmosphere friendly to learning. He/she must have the willingness to recognize every type of talent and ability and to encourage men/women of promise. He must be the professor of the open door, easily accessible to students, residents, and associates. The major goal of Dr. Edlich's comments, as he receives the Distinguished Medical Alumni Award from The Minneapolis Medical Alumni Association (Minneapolis, Minnesota, USA) is to acknowledge his distinguished colleagues and friends who have served as his teachers during his academic career. They include the following individuals: Theodore J. Edlich, III, President of Total Action Against Poverty; Elizabeth C. Edlic, Cofounder/Chairman and Chief Executive Officer of OneWorldLive; Richard F. Edlich, Jr., President of Edlich Realty; Rachel C. Edlich, Executive Vice President and Cofounder of OneWorldLive; William B. Long, III, MD, President and Medical Director of Trauma Specialists LLP; William P. Magee, MD, Cofounder and Director of Operation Smile; John Barrow, President of Coolibar Incorporated; Mary M. Barrow, Cofounder of Coolibar Incorporated; Kathryne L. Winters, Website Manager and Senior Research Assistant; Lise Borel, DDS, Independent Pharmaceutical/Biotechnical Consultant; Mary Jude Cox, MD, Board Certified Glaucoma Specialist, Teaching Staff at Wills Eye Hospital Glaucoma Service; John Wish, PhD, Member of the Board of The Association of Air Medical Services, Director of the Research Committee; and Dr. Andrew J. Gear, Plastic Surgical Resident, University of Minnesota Medical School.

HLA-DR polymorphisms influence in vivo responses to staphylococcal toxic shock syndrome toxin-1 in a transgenic mouse model.

PubMed

Krogman, A; Tilahun, A; David, C S; Chowdhary, V R; Alexander, M P; Rajagopalan, G

2017-01-01

Toxic shock syndrome toxin-1 (TSST-1) is a potent superantigen produced by Staphylococcus aureus. In addition to menstrual and nonmenstrual toxic shock syndromes, TSST-1 is also implicated in the immunopathogenesis of pneumonia, infective endocarditis, neonatal exanthematous disease, and atopic dermatitis among others. Superantigens first bind to major histocompatibility complex (MHC) class II molecules and then activate a large proportion of T cells by cross-linking their T cell receptor. As binding to MHC class II molecules is a critical step in the robust activation of the immune system by TSST-1 and other superantigens, polymorphic variations between different HLA-DR alleles could potentially influence the magnitude of immune activation and immunopathology caused by TSST-1. As TSST-1 is highly toxic to humans and given that multiple variations of alleles of HLA-DR and HLA-DQ are expressed in each individual, it is difficult to determine how HLA-DR polymorphisms quantitatively and qualitatively impact immune activation caused by TSST-1 in humans. However, such investigations can be conducted on transgenic mice lacking all endogenous MHC class II molecules and expressing specific HLA class II alleles. Therefore, transgenic mice expressing different HLA-DRB1 alleles (HLA-DRB1*15:01, HLA-DRB1*15:02, HLA-DRB1*03:01, HLA-DRB1*04:01), and sharing HLA-A1*01:01 chain, were systemically challenged with purified TSST-1 and multiple immune parameters were assessed. Among the HLA-DR alleles, mice expressing HLA-DRB1*15:01 allele elicited a significantly higher serum cytokine/chemokine response; greater splenic T cell expansion and most severe organ pathology. Our study highlights the potential utility of human leukocyte antigen (HLA) transgenic mice in understanding the impact of HLA polymorphisms on the outcomes of diseases caused by TSST-1 and other superantigens. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Circuit and synaptic mechanisms of repeated stress: Perspectives from differing contexts, duration, and development.

PubMed

Bath, Kevin G; Russo, Scott J; Pleil, Kristen E; Wohleb, Eric S; Duman, Ronald S; Radley, Jason J

2017-12-01

The current review is meant to synthesize research presented as part of a symposium at the 2016 Neurobiology of Stress workshop in Irvine California. The focus of the symposium was "Stress and the Synapse: New Concepts and Methods" and featured the work of several junior investigators. The presentations focused on the impact of various forms of stress (altered maternal care, binge alcohol drinking, chronic social defeat, and chronic unpredictable stress) on synaptic function, neurodevelopment, and behavioral outcomes. One of the goals of the symposium was to highlight the mechanisms accounting for how the nervous system responds to stress and their impact on outcome measures with converging effects on the development of pathological behavior. Dr. Kevin Bath's presentation focused on the impact of disruptions in early maternal care and its impact on the timing of hippocampus maturation in mice, finding that this form of stress drove accelerated synaptic and behavioral maturation, and contributed to the later emergence of risk for cognitive and emotional disturbance. Dr. Scott Russo highlighted the impact of chronic social defeat stress in adolescent mice on the development and plasticity of reward circuity, with a focus on glutamatergic development in the nucleus accumbens and mesolimbic dopamine system, and the implications of these changes for disruptions in social and hedonic response, key processes disturbed in depressive pathology. Dr. Kristen Pleil described synaptic changes in the bed nuclei of the stria terminalis that underlie the behavioral consequences of allostatic load produced by repeated cycles of alcohol binge drinking and withdrawal. Dr. Eric Wohleb and Dr. Ron Duman provided new data associating decreased mammalian target of rapamycin (mTOR) signaling and neurobiological changes in the synapses in response to chronic unpredictable stress, and highlighted the potential for the novel antidepressant ketamine to rescue synaptic and behavioral effects. In aggregate, these presentations showcased how divergent perspectives provide new insights into the ways in which stress impacts circuit development and function, with implications for understanding emergence of affective pathology.

Developmental considerations for substance use interventions from middle school through college.

PubMed

D'Amico, Elizabeth J; Ellickson, Phyllis L; Wagner, Eric F; Turrisi, Rob; Fromme, Kim; Ghosh-Dastidar, Bonnie; Longshore, Douglas L; McCaffrey, Daniel F; Montgomery, Marilyn J; Schonlau, Matthias; Wright, Dale

2005-03-01

This article summarizes a symposium organized by Dr. Elizabeth D'Amico and presented at the 2004 Annual Meeting of the Research Society on Alcoholism in Vancouver, Canada. The four presentations illustrate the importance of creating substance use interventions that are developmentally appropriate for youth. They represent innovative approaches to working with preteens, teenagers, and young adults. Dr. D'Amico's paper describes her research on the development of a voluntary brief intervention targeting alcohol use among middle school students. Findings indicated that by using school and community input, she was able to obtain a diverse a sample of youth across grades, sex, ethnicity, and substance use status. Dr. Ellickson's paper describes her research on Project ALERT, a school-based prevention program for middle school youth. Her findings indicate that Project ALERT worked for students at all levels of risk (low, moderate, and high) and for all students combined. Dr. Wagner's Teen Intervention Project was a randomized clinical trial to test the efficacy of a standardized Student Assistance Program for treating middle and high school students with alcohol and other drug problems. The study provided a unique opportunity to begin to examine how development may impact response to an alcohol or other drug intervention. Dr. Turrisi's paper examined processes underlying the nature of the effects of a parent intervention on college student drinking tendencies. Findings suggested that the parent intervention seems to have its impact on student drinking by reducing the influence of negative communications and decreasing the susceptibility of influences from closest friends. Dr. Kim Fromme provided concluding remarks.

Marked variation in newborn resuscitation practice: A national survey in the UK☆

PubMed Central

Mann, Chantelle; Ward, Carole; Grubb, Mark; Hayes-Gill, Barrie; Crowe, John; Marlow, Neil; Sharkey, Don

2012-01-01

Background Although international newborn resuscitation guidance has been in force for some time, there are no UK data on current newborn resuscitation practices. Objective Establish delivery room (DR) resuscitation practices in the UK, and identify any differences between neonatal intensive care units (NICU), and other local neonatal services. Methods We conducted a structured two-stage survey of DR management, among UK neonatal units during 2009–2010 (n = 192). Differences between NICU services (tertiary level) and other local neonatal services (non-tertiary) were analysed using Fisher's exact and Student's t-tests. Results There was an 89% response rate (n = 171). More tertiary NICUs institute DR CPAP than non-tertiary units (43% vs. 16%, P = 0.0001) though there was no significant difference in frequency of elective intubation and surfactant administration for preterm babies. More tertiary units commence DR resuscitation in air (62% vs. 29%, P < 0.0001) and fewer in 100% oxygen (11% vs. 41%, P < 0.0001). Resuscitation of preterm babies in particular, commences with air in 56% of tertiary units. Significantly more tertiary units use DR pulse oximeters (58% vs. 29%, P < 0.01) and titrate oxygen based on saturations. Almost all services use occlusive wrapping to maintain temperature for preterm infants. Conclusions In the UK, there are many areas of good evidence based DR practice. However, there is marked variation in management, including between units of different designation, suggesting a need to review practice to fulfil new resuscitation guidance, which will have training and resource implications. PMID:22245743

Protection against renal ischemia-reperfusion injury through hormesis? Dietary intervention versus cold exposure.

PubMed

Shushimita, Shushimita; Grefhorst, Aldo; Steenbergen, Jacobie; de Bruin, Ron W F; Ijzermans, Jan N M; Themmen, Axel P N; Dor, Frank J M F

2016-01-01

Dietary restriction (DR) and fasting (FA) induce robust protection against the detrimental effects of renal ischemia-reperfusion injury (I/RI). Several mechanisms of protection have been proposed, such as hormesis. Hormesis is defined as a life-supporting beneficial effect resulting from the cellular responses to single or multiple rounds of (mild) stress. The cold exposure (CE) model is a stress model similar to DR, and has been shown to have hormetic effects and has proved to increase longevity. CE is considered to be the most robust method to increase metabolism through activation of brown adipocytes. BAT has been considered important in etiology of obesity and its metabolic consequences. Since DR, FA, and CE models are proposed to work through hormesis, we investigated physiology of adipose tissue and effect on BAT in these models and compared them to ad libitum (AL) fed mice. We also studied the differential effect of these stress models on immunological changes, and effect of CE on renal I/RI. We show similar physiological changes in adiposity in male C57Bl/6 mice due to DR, FA and CE, but the CE mice were not protected against renal I/RI. The immunophenotypic changes observed in the CE mice were similar to the AL animals, in contrast to FA mice, that showed major immunophenotypic changes in the B and T cell development stages in primary and secondary lymphoid organs. Our findings thus demonstrate that DR, FA and CE are hormetic stress models. DR and FA protect against renal I/IR, whereas CE could not. Copyright © 2015 Elsevier Inc. All rights reserved.

Industrial Scale Energy Systems Integration; NREL (National Renewable Energy Laboratory)

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

Ruth, Mark

2015-07-28

The industrial sector consumes 25% of the total energy in the U.S. and produces 18% of the greenhouse gas (GHG) emissions. Energy Systems Integration (ESI) opportunities can reduce those values and increase the profitability of that sector. This presentation outlines several options. Combined heat and power (CHP) is an option that is available today for many applications. In some cases, it can be extended to trigeneration by adding absorbtion cooling. Demand response is another option in use by the industrial sector - in 2012, industry provided 47% of demand response capacity. A longer term option that combines the benefits ofmore » CHP with those of demand response is hybrid energy systems (HESs). Two possible HESs are described and development implications discussed. extended to trigeneration by adding absorbtion cooling. Demand response is another option in use by the industrial sector - in 2012, industry provided 47% of demand response capacity. A longer term option that combines the benefits of CHP with those of demand response is hybrid energy systems (HESs). Two possible HESs are described and development implications discussed.« less

Image restoration techniques as applied to Landsat MSS and TM data

USGS Publications Warehouse

Meyer, David

1987-01-01

Two factors are primarily responsible for the loss of image sharpness in processing digital Landsat images. The first factor is inherent in the data because the sensor's optics and electronics, along with other sensor elements, blur and smear the data. Digital image restoration can be used to reduce this degradation. The second factor, which further degrades by blurring or aliasing, is the resampling performed during geometric correction. An image restoration procedure, when used in place of typical resampled techniques, reduces sensor degradation without introducing the artifacts associated with resampling. The EROS Data Center (EDC) has implemented the restoration proceed for Landsat multispectral scanner (MSS) and thematic mapper (TM) data. This capability, developed at the University of Arizona by Dr. Robert Schowengerdt and Lynette Wood, combines restoration and resampling in a single step to produce geometrically corrected MSS and TM imagery. As with resampling, restoration demands a tradeoff be made between aliasing, which occurs when attempting to extract maximum sharpness from an image, and blurring, which reduces the aliasing problem but sacrifices image sharpness. The restoration procedure used at EDC minimizes these artifacts by being adaptive, tailoring the tradeoff to be optimal for individual images.

Termination Report

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

Bruce McCarl and Dhazngilly

2004-01-07

The results of this project include: (1) Development of econometrically estimated marginal abatement and associated production curves describing response of agricultural and forestry emissions/sink/offsets enhancements for use in integrated assessments. Curves were developed that reflected agricultural, and forestry production of traditional commodities, carbon and other greenhouse gas offsets and biofuels given signals of general commodity demand, and carbon and energy prices. (2) Integration of the non-dynamic curves from (1) into a version of the PNNL SGM integrated assessment model was done in cooperation with Dr. Ronald Sands at PNNL. The results were reported at the second DOE conference on sequestrationmore » in the paper listed and the abstract is in Annex B of this report. (3) Alternative agricultural sequestration estimates were developed in conjunction with personnel at Colorado State University using CENTURY and analyses can operate under the use of agricultural soil carbon data from either the EPIC or CENTURY models. (4) A major effort was devoted to understanding the possible role and applicable actions from agriculture. (5) Work was done with EPA and EIA to update the biofuel data and assumptions resulting in some now emerging results showing the criticality of biofuel assumptions.« less

Post-weaning social isolation of female rats, anxiety-related behavior, and serotonergic systems

PubMed Central

Lukkes, Jodi L.; Engelman, Glenn H.; Zelin, Naomi S.; Hale, Matthew W.; Lowry, Christopher A.

2012-01-01

Our previous studies have shown that post-weaning social isolation of male rats leads to sensitization of serotonergic systems and increases in anxiety-like behavior in adulthood. Although studies in humans suggest that females have an increased sensitivity to stress and risk for the development of neuropsychiatric illnesses, most studies involving laboratory rats have focused on males while females have been insufficiently studied. The objective of this study was to investigate the effects of post-weaning social isolation on subsequent responses of an anxiety-related dorsal raphe nucleus (DR)-basolateral amygdala system to pharmacological challenge with the anxiogenic drug, N-methyl-beta-carboline-3-carboxamide (FG-7142; a partial inverse agonist at the benzodiazepine allosteric site on the γ-aminobutyric acid (GABA)A receptor). Juvenile female rats were reared in isolation or in groups of three for a 3-week period from weaning to mid-adolescence, after which all rats were group-reared for an additional 2 weeks. We then used dual immunohistochemical staining for c-Fos and tryptophan hydroxylase in the DR or single immunohistochemical staining for c-Fos in the basolateral amygdala. Isolation-reared rats, but not group-reared rats, injected with FG-7142 had increased c-Fos expression within the basolateral amygdala and in serotonergic neurons in the dorsal, ventrolateral, caudal and interfascicular parts of the DR relative to appropriate vehicle-injected control groups. These data suggest that post-weaning social isolation of female rats sensitizes a DR-basolateral amygdala system to stress-related stimuli, which may lead to an increased sensitivity to stress- and anxiety-related responses in adulthood. PMID:22297173

Channel response to increased and decreased bedload supply from land use change: contrasts between two catchments

NASA Astrophysics Data System (ADS)

Kondolf, G. M.; Piégay, H.; Landon, N.

2002-06-01

The catchments of Pine Creek, Idaho, USA (200 km 2), and the Drôme River in the Drôme Department, France (1640 km 2), illustrate contrasting changes in land use, bedload sediment production, and channel response. Hard-rock mining began in the catchment of Pine Creek near the end of the 19th century and, together with road construction, timber harvest, and historically heavy grazing of uplands, resulted in increased tributary bedload yield. Increased bedload migrating to the channel, combined with removal of large cedar trees on the floodplain, resulted in channel instability, which propagated downstream over a period of decades. On many reaches of Pine Creek, active channel width has increased by over 50% since 1933. Over roughly the same time period, the Drôme River catchment was extensively reforested (after at least one century of denudation and heavy grazing) and numerous check dams were constructed on torrents to reduce erosion. As a result, the Drôme River has experienced a reduction in bedload sediment supply since the late 19th century. In addition, gravel has been extracted from some reaches. Consequently, the channel has degraded and gravel bars have been colonized with woody riparian vegetation. Channel widths in wide, braided reaches decreased from 1947 to 1970 by 60%. On Pine Creek, channel instability has resulted in bank erosion (exposing contaminated mine tailings) and increased flood hazard. On the Drôme River, degradation has undermined bridges and embankments, and lowered the water table in areas dependent on groundwater for irrigation, resulting in loss of 6 million m 3 of groundwater storage since 1960. Though they differ in drainage area by nearly an order of magnitude, Pine Creek and the Drôme River provide an excellent contrast in that they represent two sides of an epicycle of alluvial sedimentation set off in each case by land disturbance. In both cases, the most recent channel changes, though in opposite directions, were viewed as negative by river managers. On Pine Creek, managers have removed (or protected from erosion) mine tailings, and have attempted to train the stream into a more stable channel, and most rock waste piles (the principal sediment sources) have recently been controlled. On the Drôme River, managers have prohibited gravel mining and adopted new policies to permit coarse sediment to migrate through the river system.

Middle age onset short-term intermittent fasting dietary restriction prevents brain function impairments in male Wistar rats.

PubMed

Singh, Rumani; Manchanda, Shaffi; Kaur, Taranjeet; Kumar, Sushil; Lakhanpal, Dinesh; Lakhman, Sukhwinder S; Kaur, Gurcharan

2015-12-01

Intermittent fasting dietary restriction (IF-DR) is recently reported to be an effective intervention to retard age associated disease load and to promote healthy aging. Since sustaining long term caloric restriction regimen is not practically feasible in humans, so use of alternate approach such as late onset short term IF-DR regimen which is reported to trigger similar biological pathways is gaining scientific interest. The current study was designed to investigate the effect of IF-DR regimen implemented for 12 weeks in middle age rats on their motor coordination skills and protein and DNA damage in different brain regions. Further, the effect of IF-DR regimen was also studied on expression of energy regulators, cell survival pathways and synaptic plasticity marker proteins. Our data demonstrate that there was an improvement in motor coordination and learning response with decline in protein oxidative damage and recovery in expression of energy regulating neuropeptides. We further observed significant downregulation in nuclear factor kappa B (NF-κB) and cytochrome c (Cyt c) levels and moderate upregulation of mortalin and synaptophysin expression. The present data may provide an insight on how a modest level of short term IF-DR, imposed in middle age, can slow down or prevent the age-associated impairment of brain functions and promote healthy aging by involving multiple regulatory pathways aimed at maintaining energy homeostasis.

Restriction on an energy-dense diet improves markers of metabolic health and cellular aging in mice through decreasing hepatic mTOR activity.

PubMed

Schloesser, Anke; Campbell, Graeme; Glüer, Claus-Christian; Rimbach, Gerald; Huebbe, Patricia

2015-02-01

Dietary restriction (DR) on a normal low-fat diet improves metabolic health and may prolong life span. However, it is still uncertain whether restriction of an energy-dense, high-fat diet would also be beneficial and mitigate age-related processes. In the present study, we determined biomarkers of metabolic health, energy metabolism, and cellular aging in obesity-prone mice subjected to 30% DR on a high-fat diet for 6 months. Dietary-restricted mice had significantly lower body weights, less adipose tissue, lower energy expenditure, and altered substrate oxidation compared to their ad libitum-fed counterparts. Hepatic major urinary proteins (Mup) expression, which is linked to glucose and energy metabolism, and biomarkers of metabolic health, including insulin, glucose, cholesterol, and leptin/adiponectin ratio, were likewise reduced in high-fat, dietary-restricted mice. Hallmarks of cellular senescence such as Lamp2a and Hsc70 that mediate chaperone-mediated autophagy were induced and mechanistic target of rapamycin (mTOR) signaling mitigated upon high-fat DR. In contrast to DR applied in low-fat diets, anti-oxidant gene expression, proteasome activity, as well as 5'-adenosine monophosphate-activated protein kinase (AMPK) activation were not changed, suggesting that high-fat DR may attenuate some processes associated with cellular aging without the induction of cellular stress response or energy deprivation.

Nitration of the Pollen Allergen Bet v 1.0101 Enhances the Presentation of Bet v 1-Derived Peptides by HLA-DR on Human Dendritic Cells

PubMed Central

Mutschlechner, Sonja; Ferreira, Fatima; Lackner, Peter; Bohle, Barbara; Fischer, Gottfried F.; Vogt, Anne B.; Duschl, Albert

2012-01-01

Nitration of pollen derived allergens can occur by NO2 and ozone in polluted air and it has already been shown that nitrated major birch (Betula verrucosa) pollen allergen Bet v 1.0101 (Bet v 1) exhibits an increased potency to trigger an immune response. However, the mechanisms by which nitration might contribute to the induction of allergy are still unknown. In this study, we assessed the effect of chemically induced nitration of Bet v 1 on the generation of HLA-DR associated peptides. Human dendritic cells were loaded with unmodified Bet v 1 or nitrated Bet v 1, and the naturally processed HLA-DR associated peptides were subsequently identified by liquid chromatography-mass spectrometry. Nitration of Bet v 1 resulted in enhanced presentation of allergen-derived HLA-DR-associated peptides. Both the copy number of Bet v 1 derived peptides as well as the number of nested clusters was increased. Our study shows that nitration of Bet v 1 alters antigen processing and presentation via HLA-DR, by enhancing both the quality and the quantity of the Bet v 1-specific peptide repertoire. These findings indicate that air pollution can contribute to allergic diseases and might also shed light on the analogous events concerning the nitration of self-proteins. PMID:22348091

The Role of Demand Response in Reducing Water-Related Power Plant Vulnerabilities

NASA Astrophysics Data System (ADS)

Macknick, J.; Brinkman, G.; Zhou, E.; O'Connell, M.; Newmark, R. L.; Miara, A.; Cohen, S. M.

2015-12-01

The electric sector depends on readily available water supplies for reliable and efficient operation. Elevated water temperatures or low water levels can trigger regulatory or plant-level decisions to curtail power generation, which can affect system cost and reliability. In the past decade, dozens of power plants in the U.S. have curtailed generation due to water temperatures and water shortages. Curtailments occur during the summer, when temperatures are highest and there is greatest demand for electricity. Climate change could alter the availability and temperature of water resources, exacerbating these issues. Constructing alternative cooling systems to address vulnerabilities can be capital intensive and can also affect power plant efficiencies. Demand response programs are being implemented by electric system planners and operators to reduce and shift electricity demands from peak usage periods to other times of the day. Demand response programs can also play a role in reducing water-related power sector vulnerabilities during summer months. Traditionally, production cost modeling and demand response analyses do not include water resources. In this effort, we integrate an electricity production cost modeling framework with water-related impacts on power plants in a test system to evaluate the impacts of demand response measures on power system costs and reliability. Specifically, we i) quantify the cost and reliability implications of incorporating water resources into production cost modeling, ii) evaluate the impacts of demand response measures on reducing system costs and vulnerabilities, and iii) consider sensitivity analyses with cooling systems to highlight a range of potential benefits of demand response measures. Impacts from climate change on power plant performance and water resources are discussed. Results provide key insights to policymakers and practitioners for reducing water-related power plant vulnerabilities via lower cost methods.

Paeoniflorin Suppressed High Glucose-Induced Retinal Microglia MMP-9 Expression and Inflammatory Response via Inhibition of TLR4/NF-κB Pathway Through Upregulation of SOCS3 in Diabetic Retinopathy.

PubMed

Zhu, Su-Hua; Liu, Bing-Qian; Hao, Mao-Juan; Fan, Yi-Xin; Qian, Cheng; Teng, Peng; Zhou, Xiao-Wei; Hu, Liang; Liu, Wen-Tao; Yuan, Zhi-Lan; Li, Qing-Ping

2017-10-01

Diabetic retinopathy (DR) is a serious-threatening complication of diabetes and urgently needed to be treated. Evidence has accumulated indicating that microglia inflammation within the retina plays a critical role in DR. Microglial matrix metalloproteinase 9 (MMP-9) has an important role in the destruction of the integrity of the blood-retinal barrier (BRB) associated with the development of DR. MMP-9 was also considered important for regulating inflammatory responses. Paeoniflorin, a monoterpene glucoside, has a potent immunomodulatory effect on microglia. We hypothesized that paeoniflorin could significantly suppress microglial MMP-9 activation induced by high glucose and further relieve DR. BV2 cells were used to investigate the effects and mechanism of paeoniflorin. The activation of MMP-9 was measured by gelatin zymography. Cell signaling was measured by western blot assay and immunofluorescence assay. High glucose increased the activation of MMP-9 in BV2 cells, which was abolished by HMGB1, TLR4, p38 MAPK, and NF-κB inhibition. Phosphorylation of p38 MAPK induced by high glucose was decreased by TLR4 inhibition in BV2 cells. Paeoniflorin induced suppressor of cytokine signaling 3 (SOCS3) expression and reduced MMP-9 activation in BV2 cells. The effect of paeoniflorin on SOCS3 was abolished by the TLR4 inhibitor. In streptozotocin (STZ)-induced diabetes mice, paeoniflorin induced SOCS3 expression and reduced MMP-9 activation. Paeoniflorin suppressed STZ-induced IBA-1 and IL-1β expression and decreased STZ-induced high blood glucose level. In conclusion, paeoniflorin suppressed high glucose-induced retinal microglia MMP-9 expression and inflammatory response via inhibition of the TLR4/NF-κB pathway through upregulation of SOCS3 in diabetic retinopathy.

Cardiovascular and Perceptual Responses to an Ultraendurance Channel Swim: A Case Study.

PubMed

Judelson, Daniel A; Bagley, James R; Schumacher, Jennifer M; Wiersma, Lenny D

2015-09-01

Ultraendurance open water swimming presents unique physiological challenges. This case study aimed to describe cardiovascular and perceptual responses during a successful solo channel swim. Investigators followed a female swimmer's Catalina Channel (32.2 km) crossing, monitoring water temperature (T(water)) and air temperature (T(air)), distance remaining (DR), average velocity, and heart rate (HR(swim)) at regular intervals. Every 24 minutes, the swimmer reported perceived pain (on a scale of 0-10), rating of perceived exertion (RPE [scale of 6-20]), perceived thermal sensation (scale 0-8), and thirst (scale 1-9). Data are presented as mean ± SD where applicable. The participant finished in 9 hours, 2 minutes, and 48 seconds; T(water) averaged 19.1 ± 0.4ºC, and T(air) averaged 18.6 ± 0.9ºC. Her HR(swim) ranged from 148 to 155 beats/min, and thermal sensation ranged from 3 to 4. Pain inconsistently varied from 0 to 5 during the swim. The RPE remained between 12 and 14 for the first 8 hours, but increased dramatically near the end (reaching 18). Thirst sensation steadily increased throughout the swim, again reaching maximal values on completion. Physiologically and statistically significant correlations existed between thirst and DR (r = -0.905), RPE and HR(swim) (r = 0.741), RPE and DR (r = -0.694), and pain and DR (r = -0.671). The primary findings were that, despite fluctuations in perceptual stressors, the swimmer maintained a consistent exercise intensity as indicated by HR(swim); and during ultraendurance swimming, pain, RPE, and thirst positively correlated with distance swum. We hope these findings aid in the preparation and performance of future athletes by providing information on what swimmers may expect during an ultraendurance attempt and by increasing the understanding of physiological and perceptual responses during open water swimming. Copyright © 2015 Wilderness Medical Society. Published by Elsevier Inc. All rights reserved.

Reconstructing Montessori: On Being an Authentic Montessori School

ERIC Educational Resources Information Center

Monson, Michele

2006-01-01

In preparation for the centennial of Montessori education, school leaders have a unique responsibility--not only to the communities, but also to Dr. Montessori's memory--to revise the educational practices in a manner that is both respectful of her theories and responsive to a changing educational landscape. This article outlines one example of…

78 FR 21928 - Demand Response Coalition v. PJM Interconnection, L.L.C.; Notice of Complaint

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-12

... DEPARTMENT OF ENERGY Federal Energy Regulatory Commission [Docket No. EL13-57-000] Demand Response Coalition v. PJM Interconnection, L.L.C.; Notice of Complaint Take notice that on April 3, 2013, pursuant to... Demand Response Coalition \\1\\ (Complainant) filed a formal complaint against the PJM Interconnection, L.L...

Testimony of C. D. Zerby at hearing to show cause re testing operations for radioactive waste disposal, Baton Rouge, Louisiana, February 23, 1978

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

Not Available

1978-03-03

On February 23, 1978, a hearing was held in Baton Rouge, Louisiana, to show cause why the suspended drilling permits for drilling at Vacherie and Rayburn's Domes should not be permanently revoked. Presentations on behalf of the Department of Energy were made by Dr. J. D. Martinez, Dr. C. D. Zerby, and Dr. C. A. Heath. The text of this report presents the prepared testimony of C. D. Zerby. Not included are the many questions and answers. The testimony as presented may be incomplete since it was prepared from notes used by C. D. Zerby during the presentation. The presentationsmore » are concerned with responsibilities, National Waste Terminal Storage/Office of Waste Isolation programs, Louisiana exploration programs, Avery Island, environmental studies, facility description, other study areas, and previous communications regarding the program. (JRD)« less

Abidjan: new challenges. UNAIDS focus.

PubMed

1998-03-01

This article focuses on the challenges as a result of the AIDS epidemic in Africa. Updated surveillance uncovers 16,000 new infections a day and 30 million people are now living with HIV/AIDS. In addition, 1 in 100 adults in the 15-49 age group are infected with HIV and only 1 in 10 infected persons are aware of their HIV status. At the 10th International Conference on AIDS and Sexually Transmitted Diseases in Africa in 1997, Dr. Peter Piot, Executive Director of the Joint UN Program on HIV/AIDS, drew attention to the importance of unmasking what is in many places still an invisible epidemic. Dr. Piot said that the alarming situation calls for an unprecedented global effort. In conclusion, Dr. Piot issued these challenges of: breaking the silence, focusing on the next generation, making AIDS a development issue, and ensuring solidarity to help Africa scale up its response to the epidemic.

Modeling the relationship between body weight and energy intake: A molecular diffusion-based approach

PubMed Central

2012-01-01

Background Body weight is at least partly controlled by the choices made by a human in response to external stimuli. Changes in body weight are mainly caused by energy intake. By analyzing the mechanisms involved in food intake, we considered that molecular diffusion plays an important role in body weight changes. We propose a model based on Fick's second law of diffusion to simulate the relationship between energy intake and body weight. Results This model was applied to food intake and body weight data recorded in humans; the model showed a good fit to the experimental data. This model was also effective in predicting future body weight. Conclusions In conclusion, this model based on molecular diffusion provides a new insight into the body weight mechanisms. Reviewers This article was reviewed by Dr. Cabral Balreira (nominated by Dr. Peter Olofsson), Prof. Yang Kuang and Dr. Chao Chen. PMID:22742862

76 FR 20713 - Bureau of International Labor Affairs; Office of Trade and Labor Affairs; Request for Comments on...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-04-13

...This notice is a request for comments from the public to assist the Secretary of Labor and the United States Trade Representative in preparing a report on labor capacity-building efforts under Chapter 16 (``the Labor Chapter'') and Annex 16.5 of the Dominican Republic--Central America--United States Free Trade Agreement (``the CAFTA-DR''), as well as efforts made by the CAFTA-DR countries to implement the recommendations contained in the report entitled ``The Labor Dimension in Central America and the Dominican Republic--Building on Progress: Strengthening Compliance and Enhancing Capacity'' (``the White Paper''). This report is required under the Dominican Republic-- Central America--United States Free Trade Agreement Implementation Act (``the CAFTA-DR Implementation Act''). The reporting function and the responsibility for soliciting public comments required under this Act were assigned to the Secretary of Labor, in consultation with the United States Trade Representative.

Effects of coating spherical iron oxide nanoparticles

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

Milosevic, Irena; Motte, Laurence; Aoun, Bachir

2017-01-01

We investigate the effect of several coatings applied in biomedical applications to iron oxide nanoparticles on the size, structure and composition of the particles. The four structural techniques employed - TEM, DLS, VSM, SAXS and EXAFS - show no significant effects of the coatings on the spherical shape of the bare nanoparticles, the average sizes or the local order around the Fe atoms. The NPs coated with hydroxylmethylene bisphosphonate or catechol have a lower proportion of magnetite than the bare and citrated ones, raising the question whether the former are responsible for increasing the valence state of the oxide onmore » the NP surfaces and lowering the overall proportion of magnetite in the particles. VSM measurements show that these two coatings lead to a slightly higher saturation magnetization than the citrate. This article is part of a Special Issue entitled "Science for Life" Guest Editor: Dr. Austen Angell, Dr. Salvatore Magazu and Dr. Federica Migliardo.« less

Expression of lycopene biosynthesis genes fused in line with Shine-Dalgarno sequences improves the stress-tolerance of Lactococcus lactis.

PubMed

Dong, Xiangrong; Wang, Yanping; Yang, Fengyuan; Zhao, Shanshan; Tian, Bing; Li, Tao

2017-01-01

Lycopene biosynthetic genes from Deinococcus radiodurans were co-expressed in Lactococcus lactis to produce lycopene and improve its tolerance to stress. Lycopene-related genes from D. radiodurans, DR1395 (crtE), DR0862 (crtB), and DR0861 (crtI), were fused in line with S hine-Dalgarno (SD) sequences and co-expressed in L. lactis. The recombinant strain produced 0.36 mg lycopene g -1  dry cell wt after 48 h fermentation. The survival rate to UV irradiation of the recombinant strain was higher than that of the non-transformed strain. The L. lactis with co-expressed genes responsible for lycopene biosynthesis from D. radiodurans produced lycopene and exhibited increased resistance to UV stress, suggesting that the recombinant strain has important application potential in food industry.

Emerging Technologies Program Integration Report. Volume 1. Narrative, Analyses and Assessment

DTIC Science & Technology

1987-05-04

James S. (T) 31. GREGG, Dr. Michael C. (T) 61. REDDY, Dr. Raj (T) 2. ATLAS, Dr. David (T) 32. HADDAD, Dr. Genevieve M. 62. REDIKER, Dr. Robert H. 3...Dr. Martin C. 83. WEEKS, Dr. Wilford 6 24. FAETH, Dr. Gerald 54. MUNSON, Mr. John 84. WEINTRAUB, Dr. Daniel 1. (T) 25. FETTERMAN , Dr. Harold 55...T) 2. ATLAS, Dr. David (T) 32. HADDAD, Dr. Genevieve M. 62. REDIKER, Dr. Robert H. 3. BALDESCHWIELER, Dr. John (T) 33. HAMMOND, Dr. George S. 63

Demand Intensity, Market Parameters and Policy Responses towards Demand and Supply of Private Supplementary Tutoring in China

ERIC Educational Resources Information Center

Kwok, Percy Lai Yin

2010-01-01

Based on some longitudinal studies of private tutoring in twelve cities, towns, municipalities and provinces of China, the paper endeavours to depict demand intensity, articulate market parameters and reflect on policy responses towards the demand-supply mechanism of the vast shadowy educational phenomena at primary and secondary levels. Such…

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

Marks, Gary; Wilcox, Edmund; Olsen, Daniel

California agricultural irrigation consumes more than ten billion kilowatt hours of electricity annually and has significant potential for contributing to a reduction of stress on the grid through demand response, permanent load shifting, and energy efficiency measures. To understand this potential, a scoping study was initiated for the purpose of determining the associated opportunities, potential, and adoption challenges in California agricultural irrigation. The primary research for this study was conducted in two ways. First, data was gathered and parsed from published sources that shed light on where the best opportunities for load shifting and demand response lie within the agriculturalmore » irrigation sector. Secondly, a small limited survey was conducted as informal face-to-face interviews with several different California growers to get an idea of their ability and willingness to participate in permanent load shifting and/or demand response programs. Analysis of the data obtained from published sources and the survey reveal demand response and permanent load shifting opportunities by growing region, irrigation source, irrigation method, grower size, and utility coverage. The study examines some solutions for demand response and permanent load shifting in agricultural irrigation, which include adequate irrigation system capacity, automatic controls, variable frequency drives, and the contribution from energy efficiency measures. The study further examines the potential and challenges for grower acceptance of demand response and permanent load shifting in California agricultural irrigation. As part of the examination, the study considers to what extent permanent load shifting, which is already somewhat accepted within the agricultural sector, mitigates the need or benefit of demand response for agricultural irrigation. Recommendations for further study include studies on how to gain grower acceptance of demand response as well as other related studies such as conducting a more comprehensive survey of California growers.« less

77 FR 48967 - Marine Mammals; File No. 17350

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-15

... permit has been issued to the North Slope Borough Department of Wildlife Management, P.O. Box 69, Barrow, AK 99723 [Taqulik Hepa, Responsible Party; Dr. John C. George, Principal Investigator] to collect...

77 FR 37000 - Marine Mammals; File No. 814-1899

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-20

... hereby given that the North Slope Borough Department of Wildlife Management, P.O. Box 69, Barrow, AK 99723 [Taqulik Hepa, Responsible Party; Dr. John C. George, Principal Investigator], has been issued a...

Modelling surface hydrology with DR2-SAGA 1.0: development of a user-friendly interface for hillslope water balance assessments

NASA Astrophysics Data System (ADS)

López-Montero, Teresa; López-Vicente, Manuel; Navas, Ana

2013-04-01

Soil moisture variability and the depth of water stored in the arable layer of the soil are important topics in agricultural research and rangeland management. Additionally, runoff triggers soil detachment and sediment delivery, and thus is one of the most important factors in the soil erosion dynamic. Overland flow generation and accumulation are non-linear and scale-dependent processes and the development of prediction models helps researchers evaluate different scenarios at different temporal and spatial scales. In this study, we present the DR2-SAGA 1.0 module to the scientific community. The DR2 (Distributed Rainfall-Runoff) water balance model computes the depth of water stored within the soil profile (Waa) distinguishing five scenarios of the upslope contributing area, infiltration processes and climatic parameters, and assesses the soil moisture status (SMS) throughout the year for an average monthly rainfall event. The SAGA program is a free Geographical Information System (GIS) with support for vector and, specially, raster data. Its foundation is its Application Programming Interface (API), which provides data object models and basic definitions for the programming of scientific modules. Module libraries contain the scientific methods and are developed using C++ code. The new module was run in a medium size mountain Mediterranean catchment (246 ha; Spanish Central Pre-Pyrenees) at high spatial resolution (5 x 5 meters of cell size). The Estaña Lakes Catchment is affected by karstic processes which explain the presence of 15 endorheic sub-catchments and three fresh-water lakes. Additionally, this area is ungauged and offers the opportunity to test the performance of the new module in a non-conventional landscape. DR2-SAGA 1.0 demands 16 inputs and generates monthly and annual maps of initial and effective runoff depth, Waa and SMS. One user-friendly tab was created with SAGA 2.0.8 for each input and output file. The new module also includes a water balance routine to obtain accurate maps of effective cumulative runoff for any type of accumulation algorithm used. In order to make more readable the results and their legends, a predefined layout was created for each derived map. Further research seeks the development of an equation to add the Effective Hydrological Depth factor in order to improve the reliability of the model in shallow soils. A basic statistical analysis package will also appear in the next version of the module. The development of the DR2-SAGA 1.0 module in the open-source SAGA platform boosts the simulation capacity of the DR2 model in comparison with its application in other commercial GIS software. As a result, we present a scientific module that brings together the set of equations, mathematical calculations and GIS operations included in the DR2 model. DR2-SAGA 1.0 provides a powerful and efficient tool with an intuitive graphical user interface having a low computational cost. In general, DR2-SAGA 1.0 shows great potential for hydrological studies in small and medium size catchments and can be used by both advanced and non-expert users. The new module will be available in the web site of our research center in spring 2013.