Science.gov

Sample records for activity key results

  1. Job Interviews: Keys for Results

    ERIC Educational Resources Information Center

    Miller, Donald S.; Catt, Stephen E.; Slocombe, Thomas E.

    2014-01-01

    Many students seem disinterested in learning to handle employment interviews effectively. This article discusses students' motivation to become skilled interviewees and steps educators and counselors can take to increase students' interest in this crucial career activity. The article also discusses mistakes students frequently make during…

  2. New Security Results on Encrypted Key Exchange

    SciTech Connect

    Bresson, Emmanuel; Chevassut, Olivier; Pointcheval, David

    2003-12-15

    Schemes for encrypted key exchange are designed to provide two entities communicating over a public network, and sharing a (short) password only, with a session key to be used to achieve data integrity and/or message confidentiality. An example of a very efficient and ''elegant'' scheme for encrypted key exchange considered for standardization by the IEEE P1363 Standard working group is AuthA. This scheme was conjectured secure when the symmetric-encryption primitive is instantiated via either a cipher that closely behaves like an ''ideal cipher,'' or a mask generation function that is the product of the message with a hash of the password. While the security of this scheme in the former case has been recently proven, the latter case was still an open problem. For the first time we prove in this paper that this scheme is secure under the assumptions that the hash function closely behaves like a random oracle and that the computational Diffie-Hellman problem is difficult. Furthermore, since Denial-of-Service (DoS) attacks have become a common threat we enhance AuthA with a mechanism to protect against them.

  3. Quasi-normal frequencies: key analytic results

    NASA Astrophysics Data System (ADS)

    Boonserm, Petarpa; Visser, Matt

    2011-03-01

    The study of exact quasi-normal modes [QNMs], and their associated quasi-normal frequencies [QNFs], has had a long and convoluted history — replete with many rediscoveries of previously known results. In this article we shall collect and survey a number of known analytic results, and develop several new analytic results — specifically we shall provide several new QNF results and estimates, in a form amenable for comparison with the extant literature. Apart from their intrinsic interest, these exact and approximate results serve as a backdrop and a consistency check on ongoing efforts to find general model-independent estimates for QNFs, and general model-independent bounds on transmission probabilities. Our calculations also provide yet another physics application of the Lambert W function. These ideas have relevance to fields as diverse as black hole physics, (where they are related to the damped oscillations of astrophysical black holes, to greybody factors for the Hawking radiation, and to more speculative state-counting models for the Bekenstein entropy), to quantum field theory (where they are related to Casimir energies in unbounded systems), through to condensed matter physics, (where one may literally be interested in an electron tunnelling through a physical barrier).

  4. Key results from SB8 simulant flowsheet studies

    SciTech Connect

    Koopman, D. C.

    2013-04-26

    Key technically reviewed results are presented here in support of the Defense Waste Processing Facility (DWPF) acceptance of Sludge Batch 8 (SB8). This report summarizes results from simulant flowsheet studies of the DWPF Chemical Process Cell (CPC). Results include: Hydrogen generation rate for the Sludge Receipt and Adjustment Tank (SRAT) and Slurry Mix Evaporator (SME) cycles of the CPC on a 6,000 gallon basis; Volume percent of nitrous oxide, N2O, produced during the SRAT cycle; Ammonium ion concentrations recovered from the SRAT and SME off-gas; and, Dried weight percent solids (insoluble, soluble, and total) measurements and density.

  5. Active magnetic radiation shielding system analysis and key technologies.

    PubMed

    Washburn, S A; Blattnig, S R; Singleterry, R C; Westover, S C

    2015-01-01

    Many active magnetic shielding designs have been proposed in order to reduce the radiation exposure received by astronauts on long duration, deep space missions. While these designs are promising, they pose significant engineering challenges. This work presents a survey of the major systems required for such unconfined magnetic field design, allowing the identification of key technologies for future development. Basic mass calculations are developed for each system and are used to determine the resulting galactic cosmic radiation exposure for a generic solenoid design, using a range of magnetic field strength and thickness values, allowing some of the basic characteristics of such a design to be observed. This study focuses on a solenoid shaped, active magnetic shield design; however, many of the principles discussed are applicable regardless of the exact design configuration, particularly the key technologies cited.

  6. Key uncertainties in climate change policy: Results from ICAM-2

    SciTech Connect

    Dowlatabadi, H.; Kandlikar, M.

    1995-12-31

    A critical aspect of climate change decision-making is uncertainties in current understanding of the socioeconomic, climatic and biogeochemical processes involved. Decision-making processes are much better informed if these uncertainties are characterized and their implications understood. Quantitative analysis of these uncertainties serve to: inform decision makers about the likely outcome of policy initiatives; and help set priorities for research so that outcome ambiguities faced by the decision-makers are reduced. A family of integrated assessment models of climate change have been developed at Carnegie Mellon. These models are distinguished from other integrated assessment efforts in that they were designed from the outset to characterize and propagate parameter, model, value, and decision-rule uncertainties. The most recent of these models is ICAM 2.0. This model includes demographics, economic activities, emissions, atmospheric chemistry, climate change, sea level rise and other impact modules and the numerous associated feedbacks. The model has over 700 objects of which over 1/3 are uncertain. These have been grouped into seven different classes of uncertain items. The impact of uncertainties in each of these items can be considered individually or in combinations with the others. In this paper we demonstrate the relative contribution of various sources of uncertainty to different outcomes in the model. The analysis shows that climatic uncertainties are most important, followed by uncertainties in damage calculations, economic uncertainties and direct aerosol forcing uncertainties. Extreme uncertainties in indirect aerosol forcing and behavioral response to climate change (adaptation) were characterized by using bounding analyses; the results suggest that these extreme uncertainties can dominate the choice of policy outcomes.

  7. Prominences: The Key to Understanding Solar Activity

    NASA Technical Reports Server (NTRS)

    Karpen, Judy T.

    2011-01-01

    Prominences are spectacular manifestations of both quiescent and eruptive solar activity. The largest examples can be seen with the naked eye during eclipses, making prominences among the first solar features to be described and catalogued. Steady improvements in temporal and spatial resolution from both ground- and space-based instruments have led us to recognize how complex and dynamic these majestic structures really are. Their distinguishing characteristics - cool knots and threads suspended in the hot corona, alignment along inversion lines in the photospheric magnetic field within highly sheared filament channels, and a tendency to disappear through eruption - offer vital clues as to their origin and dynamic evolution. Interpreting these clues has proven to be contentious, however, leading to fundamentally different models that address the basic questions: What is the magnetic structure supporting prominences, and how does so much cool, dense plasma appear in the corona? Despite centuries of increasingly detailed observations, the magnetic and plasma structures in prominences are poorly known. Routine measurements of the vector magnetic field in and around prominences have become possible only recently, while long-term monitoring of the underlying filament-channel formation process also remains scarce. The process responsible for prominence mass is equally difficult to establish, although we have long known that the chromosphere is the only plausible source. As I will discuss, however, the motions and locations of prominence material can be used to trace the coronal field, thus defining the magnetic origins of solar eruptions. A combination of observations, theory, and numerical modeling must be used to determine whether any of the competing theories accurately represents the physics of prominences. I will discuss the criteria for a successful prominence model, compare the leading models, and present in detail one promising, comprehensive scenario for

  8. Increase in physical activities in kindergarten children with cerebral palsy by employing MaKey-MaKey-based task systems.

    PubMed

    Lin, Chien-Yu; Chang, Yu-Ming

    2014-09-01

    In this study, we employed Flash- and Scratch-based multimedia by using a MaKey-MaKey-based task system to increase the motivation level of children with cerebral palsy to perform physical activities. MaKey MaKey is a circuit board that converts physical touch to a digital signal, which is interpreted by a computer as a keyboard message. In this study, we used conductive materials to control this interaction. This study followed single-case design using ABAB models in which A indicated the baseline and B indicated the intervention. The experiment period comprised 1 month and a half. The experimental results demonstrated that in the case of two kindergarten children with cerebral palsy, their scores were considerably increased during the intervention phrases. The developmental applications of the results are also discussed.

  9. Active listening: The key of successful communication in hospital managers

    PubMed Central

    Jahromi, Vahid Kohpeima; Tabatabaee, Seyed Saeed; Abdar, Zahra Esmaeili; Rajabi, Mahboobeh

    2016-01-01

    Introduction One of the important causes of medical errors and unintentional harm to patients is ineffective communication. The important part of this skill, in case it has been forgotten, is listening. The objective of this study was to determine whether managers in hospitals listen actively. Methods This study was conducted between May and June 2014 among three levels of managers at teaching hospitals in Kerman, Iran. Active Listening skill among hospital managers was measured by self-made Active Listening Skill Scale (ALSS), which consists of the key elements of active listening and has five subscales, i.e., Avoiding Interruption, Maintaining Interest, Postponing Evaluation, Organizing Information, and Showing Interest. The data were analyzed by IBM-SPSS software, version 20, and the Pearson product-moment correlation coefficient, the chi-squared test, and multiple linear regressions. Results The mean score of active listening in hospital managers was 2.32 out of 3.The highest score (2.27) was obtained by the first-level managers, and the top managers got the lowest score (2.16). Hospital mangers were best in showing interest and worst in avoiding interruptions. The area of employment was a significant predictor of avoiding interruption and the managers’ gender was a strong predictor of skill in maintaining interest (p < 0.05). The type of management and education can predict postponing evaluation, and the length of employment can predict showing interest (p < 0.05). Conclusion There is a necessity for the development of strategies to create more awareness among the hospital managers concerning their active listening skills. PMID:27123221

  10. Exploring Key Sustainable Development Themes through Learning Activities

    ERIC Educational Resources Information Center

    Cruickshank, Heather; Fenner, Richard

    2012-01-01

    Purpose: The purpose of the paper is to examine how a number of key themes are introduced in the Master's programme in Engineering for Sustainable Development, at Cambridge University, through student-centred activities. These themes include dealing with complexity, uncertainty, change, other disciplines, people, environmental limits, whole life…

  11. Monitoring the Future: National Results on Adolescent Drug Use. Overview of Key Findings, 2006

    ERIC Educational Resources Information Center

    Johnston, Lloyd D., O'Malley, Patrick M.; Bachman, Jerald G.; Schulenberg, John E.

    2007-01-01

    This report provides a summary of drug use trends from a survey of nearly 50,000 eighth-, tenth-, and twelfth- grade students nationwide. It also includes perceived risk, personal disapproval, and perceived availability of each drug by this group. A synopsis of the methods used in the study and an overview of the key results from the 2006 survey…

  12. Key Performance Indicators: From Promise to Payoff. The Productivity for Results Series No. 2

    ERIC Educational Resources Information Center

    Casserly, Michael; Eugene, Michael

    2014-01-01

    This paper draws upon the expertise of two leading educators, Michael Casserly, director of the Council of the Great City Schools, and Michael Eugene, chief operating officer of the Orange County Public Schools in Florida. They outline a set of key performance indicators that some urban districts use to benchmark the results of their operating…

  13. Activeness as a key to counter democratic balance

    NASA Astrophysics Data System (ADS)

    Qian, Shen; Liu, Yijun; Galam, Serge

    2015-08-01

    According to the classic Galam model of opinion dynamics, each agent participates at each update of an opinion interaction. While the scheme gives everyone the same chance to influence others, in reality, social activity and influence vary considerably from one agent to another. To account for such a feature, we introduce a new individual attribute-"activeness"-which makes some agents more inclined than others at engaging in local discussions. To enhance the corresponding effect, opinion updates are shifted from all-out agent interaction cycles to few agent interaction cycles. Using dynamic analysis and simulations the resulting model is found to exhibit a "Minority Counteroffensive" phenomenon, which under some initial conditions makes the minority to win the opinion competition despite a threshold tipping point at fifty percent. The associated probabilistic phenomenon persists in the case "activeness" is held equal for all agents. The effect of "opinion leaders" is also investigated. Indeed, a leader is an inflexible agent, i.e., an agent who does not change opinion. The results reveal that two opinion leaders with moderate social influence may have a stronger effect than one opinion leader with a strong social influence. The model may shed a new light to the understanding of opinion formation and public voting.

  14. Keys to active ageing: new communication technologies and lifelong learning.

    PubMed

    Díaz-López, M Del Pilar; López-Liria, Remedios; Aguilar-Parra, José M; Padilla-Góngora, David

    2016-01-01

    The purpose of this study is to describe the creation and implementation of an ICT education program for the elderly in various Active Participation Centers in Almería (Spain), assessing its impact on quality of life. From a randomized sample of 200 individuals over the age of 55. Results reveal a high degree of participant satisfaction (76.6 %), as well as improvements in quality of life as compared to the control group after the 3 month program health factor: p = 0.004; leisure and activity factor: p = 0.001; Satisfaction with Life Factor: p < 0.001. The analysis conducted to determine the influence of age and gender on quality of life indicates that there are statistically significant differences in regards to age (the younger groups had higher scores) and gender (the males). This study may serve to facilitate similar works that promotes on-going education in different locations and across the lifespan.

  15. Exercise and Activity: Key Elements in the Management of OI

    MedlinePlus

    ... in both children and adults. Research indicates that physical activity is important because it promotes: general health through cardiovascular fitness mental alertness weight control improved sleep quality ...

  16. A novel active contour model for unsupervised low-key image segmentation

    NASA Astrophysics Data System (ADS)

    Mei, Jiangyuan; Si, Yulin; Karimi, Hamid; Gao, Huijun

    2013-06-01

    Unsupervised image segmentation is greatly useful in many vision-based applications. In this paper, we aim at the unsupervised low-key image segmentation. In low-key images, dark tone dominates the background, and gray level distribution of the foreground is heterogeneous. They widely exist in the areas of space exploration, machine vision, medical imaging, etc. In our algorithm, a novel active contour model with the probability density function of gamma distribution is proposed. The flexible gamma distribution gives a better description for both of the foreground and background in low-key images. Besides, an unsupervised curve initialization method is designed, which helps to accelerate the convergence speed of curve evolution. The experimental results demonstrate the effectiveness of the proposed algorithm through comparison with the CV model. Also, one real-world application based on our approach is described in this paper.

  17. The mid-IR and near-IR interferometry of AGNs: key results and their implications

    NASA Astrophysics Data System (ADS)

    Kishimoto, M.

    2015-09-01

    Infrared interferometry has been very productive in directly probing the structure of AGNs at sub-pc scales. With tens of objects already probed in the mid-IR and near-IR, I will summarize the key results and im- plications from this direct exploration. The Keck interferometry in the near-IR and VLTI in the mid-IR shaped the luminosity dependence of the torus size and structure, while the latter also revealed an equatorial structure at several Rsub (dust sublimation radius), and a polar-elongated region at a few tens of Rsub. Notably, this polar component seems to dominate the compact mid-IR flux. This component can persuasively be attributed to a polar outflow. However, interferometry, through emissivity estimations, also indicates that it is not a UV-optically-thin cloud but participating in the obscuration of the nucleus. I will discuss how to accommodate all these facts to build a consistent picture.

  18. Client satisfaction. Operations research activities and results.

    PubMed

    1998-06-01

    Operations research (OR) is a major component of the Quality Assurance Project's (QAP) strategy for improving the quality of health care delivery worldwide. QAP's Operations Research Program aims to improve the feasibility, utility, and cost-effectiveness of quality assurance strategies in developing countries. QAP and its field partners work to maximize the utility of each field study's findings. As such, the project hopes to disseminate information on all aspects of important OR projects, from the initial design to implementation and results. Over the course of the project, QAP's staff and their partners will develop studies in 16 technical areas. One key area of interest is the study of client satisfaction with health care delivery. The project currently has two major studies on client satisfaction underway in Niger and Peru. Phase one results from the Niger research and QAP and the Max Salud Institute in Peru are discussed.

  19. Key results for the NRC`s Short Cracks in Piping and Piping Welds Research Program

    SciTech Connect

    Wilkowski, G.; Krishnaswamy, P.; Brust, F.

    1995-04-01

    The overall objective of the Short Cracks in Piping and Piping Welds Program is to verify and improve engineering analyses to predict the fracture behavior of circumferentially cracked pipe under quasi-static loading with particular attention to crack lengths typically used in LBB or flaw evaluation criteria. The USNCRC program at Battelle was initiated in March 1990 and is scheduled to be completed in December 1994. This paper discusses key results from the overall program with particular emphasis on the efforts since the last WRSIM meeting. The program consists of eight technical tasks as listed below: task 1 short through-wall-cracked (TWC) pipe evaluations; task 2 short surface-cracked (SC) pipe evaluations; task 3 bi-metallic weld crack evaluations; task 4 dynamic strain aging and crack instabilities; task 5 fracture evaluations of anisotropic pipe; task 6 crack-opening-area evaluations; task 7 NRCPIPE code improvements; task 8 additional efforts. Task 8 is a collection of new efforts initiated during the coarse of the program. A list of the full-scale pipe experiments in this program is given in Table 1. All of the experiments have been completed. The most recent accomplishments in each of the tasks listed above are discussed below. The details of all the results in the eight tasks are published in the semiannual reports as well as topical reports from the program.

  20. Parker Lecture - Prominences: the key to understanding solar activity

    NASA Astrophysics Data System (ADS)

    Karpen, Judith T.

    2011-05-01

    Prominences are spectacular manifestations of both quiescent and eruptive solar activity. The largest examples can be seen with the naked eye during eclipses, making prominences among the first solar features to be described and catalogued. Steady improvements in temporal and spatial resolution from both ground- and space-based instruments have led us to recognize how complex and dynamic these majestic structures really are. Their distinguishing characteristics - cool knots and threads suspended in the hot corona, alignment along inversion lines in the photospheric magnetic field within highly sheared filament channels, and a tendency to disappear through eruption - offer vital clues as to their origin and dynamic evolution. Interpreting these clues has proven to be contentious, however, leading to fundamentally different models that address the basic questions: What is the magnetic structure supporting prominences, and how does so much cool, dense plasma appear in the corona? Despite centuries of increasingly detailed observations, the magnetic and plasma structures in prominences are poorly known. Routine measurements of the vector magnetic field in and around prominences have become possible only recently, while long-term monitoring of the underlying filament-channel formation process remains scarce. The process responsible for prominence mass is equally difficult to establish, although we have long known that the chromosphere is the only plausible source. As I will discuss, however, the motions and locations of prominence material can be used to trace the coronal field, thus defining the magnetic origins of solar eruptions. A combination of observations, theory, and numerical modeling must be used to determine whether any of the competing theories accurately represents the physics of prominences. I will discuss the criteria for a successful prominence model, compare the leading models, and present in detail one promising, comprehensive scenario for prominence

  1. North Atlantic Aerosol Properties and Direct Radiative Effects: Key Results from TARFOX and ACE-2

    NASA Technical Reports Server (NTRS)

    Russell, P. B.; Livingston, J. M.; Schmid, B.; Bergstrom, R. A.; Hignett, P.; Hobbs, P. V.; Durkee, P. A.; Condon, Estelle (Technical Monitor)

    1998-01-01

    Aerosol effects on atmospheric radiative fluxes provide a forcing function that can change the climate in potentially significant ways. This aerosol radiative Forcing is a major source of uncertainty in understanding the observed climate change of the past century and in predicting, future climate. To help reduce this uncertainty, the International Global Atmospheric Chemistry Project (IGAC) has endorsed a series of multiplatform aerosol field campaigns. The Tropospheric Aerosol Radiative Forcing Observational Experiment (TARFOX) and the second Aerosol Characterization Experiment (ACE-2) were the first IGAC campaigns to address the impact of anthropogenic aerosols. Both TARFOX and ACE-2 gathered extensive data sets on aerosol properties and radiative effects. TARFOX focused on the urban-industrial haze plume flowing from the eastern United States over the western Atlantic Ocean, whereas ACE-2 studied aerosols carried over the eastern Atlantic from both European urban/industrial and African mineral sources. These aerosols often have a marked influence on the top-of-atmosphere radiances measured by satellites, as illustrated in Figure 1. Shown there are contours of aerosol optical depth derived from radiances measured by the AVHRR sensor on the NOAA-11 satellite. The contours readily show that aerosols originating in North America, Europe, and Africa impact the radiative properties of air over the North Atlantic. However, the accurate derivation of flux chances, or radiative forcing, from the satellite-measured radiances or 'etrieved optical depths remains a difficult challenge. In this paper we summarize key Initial results from TARFOX and, to a lesser extent ACE-2, with a focus on those results that allow an improved assessment of the flux changes caused by North Atlantic aerosols at middle and high latitudes.

  2. North Atlantic Aerosol Properties and Direct Radiative Effects: Key Results from TARFOX and ACE-2

    NASA Technical Reports Server (NTRS)

    Russell, P. B.; Livingston, J. M.; Schmid, B.; Bergstrom, Robert A.; Hignett, P.; Hobbs, P. V.; Durkee, P. A.

    2000-01-01

    Aerosol effects on atmospheric radiative fluxes provide a forcing function that can change the climate In potentially significant ways. This aerosol radiative forcing is a major source of uncertainty in understanding the observed climate change of the past century and in predicting future climate. To help reduce this uncertainty, the International Global Atmospheric Chemistry Project (IGAC) has endorsed a series of multiplatform aerosol field campaigns. The Tropospheric Aerosol Radiative Forcing Observational Experiment (TARFOX) and the second Aerosol Characterization Experiment (ACE-2) were the first IGAC campaigns to address the impact of anthropogenic aerosols, Both TARFOX and ACE-2 gathered extensive data sets on aerosol properties and radiative effects, TARFOX focused on the urban-industrial haze plume flowing from the eastern United States over the western Atlantic Ocean, whereas ACE-2 studied aerosols carried over the eastern Atlantic from both European urban/industrial and African mineral sources. These aerosols often have a marked influence on the top-of-atmosphere radiances measured by satellites. Shown there are contours of aerosol optical depth derived from radiances measured by the AVHRR sensor on the NOAA-11 satellite. The contours readily show that aerosols originating in North America, Europe, and Africa impact the radiative properties of air over the North Atlantic. However, the accurate derivation of flux changes, or radiative forcing, from the satellite measured radiances or retrieved optical depths remains a difficult challenge. In this paper we summarize key initial results from TARFOX and, to a lesser extent, ACE-2, with a focus on those results that allow an improved assessment of the flux changes caused by North Atlantic aerosols at middle latitudes.

  3. Key questions resulting from the JUPITER trial assessing cardiovascular disease intervention with rosuvastatin.

    PubMed

    Rashid, Shirya

    2009-12-31

    THIS PAPER PRESENTS AN ANALYSIS OF THE RECENTLY PUBLISHED JUSTIFICATION FOR THE USE OF STATINS IN PREVENTION (JUPITER: an intervention trial evaluating rosuvastatin) trial, which tested the statin rosuvastatin in apparently healthy individuals with no prior cardiovascular (CVD) disease and with normal plasma low density lipoprotein (LDL) cholesterol concentrations but with raised plasma high sensitivity C-reactive protein (hsCRP) levels. The rate of the combined primary CVD endpoint was significantly reduced in the treatment arm after a median of under 2 years. The JUPITER trial is distinct from previous studies examining statin use in primary prevention groups because the target group for drug therapy was apparently healthy men and women at low or intermediate risk for developing CVD. On the basis of JUPITER's findings, there are key questions that should be assessed on the therapeutic intervention of CVD regarding: the primary prevention groups that should be targeted for statin therapy, the utility of targets in addition to plasma LDL cholesterol levels, and the need to consider the metabolic state of individuals targeted for therapy (including the presence of obesity and inflammation). The conclusion from the current analysis is that the JUPITER results warrant further LDL cholesterol lowering than is currently targeted in primary prevention groups that have a pre-existing condition or lifestyle that elevates CVD risk but still do not have a high global CVD risk (as assessed with current algorithms). This group is not captured in current widely used CVD risk calculations, however, with the identification of useful biomarkers, such as hsCRP, this group can be better identified and targeted for intervention.

  4. Monitoring the Future National Results on Adolescent Drug Use: Overview of Key Findings, 2001.

    ERIC Educational Resources Information Center

    Johnston, Lloyd D.; O'Malley, Patrick M.; Bachman, Jerald G.

    This report presents an overview of the key findings from the Monitoring the Future 2001 nationwide survey of 8th, 10th, and 12th grade students. A particular emphasis is placed on recent trends in the use of licit and illicit drugs. Trends in the levels of perceived risk and personal disapproval associated with each drug--which this study has…

  5. Monitoring the Future: National Results on Adolescent Drug Use. Overview of Key Findings, 2002.

    ERIC Educational Resources Information Center

    Michigan Univ., Ann Arbor. Inst. for Social Research.

    This report presents an overview of the key findings from the Monitoring the Future 2002 nationwide survey of 8th, 10th, and 12th grade students. A particular emphasis is placed on recent trends in the use of licit and illicit drugs. Trends in the levels of perceived risk and personal disapproval associated with each drug--which this study has…

  6. Gemini Planet Imager Exoplanet Survey: Key Results Two Years Into The Survey

    NASA Astrophysics Data System (ADS)

    Marchis, Franck; Rameau, Julien; Nielsen, Eric L.; De Rosa, Robert J.; Esposito, Thomas; Draper, Zachary H.; Macintosh, Bruce; Graham, James R.; GPIES

    2016-10-01

    The Gemini Planet Imager Exoplanet Survey (GPIES) is targeting 600 young, nearby stars using the GPI instrument. We report here on recent results obtained with this instrument from our team.Rameau et al. (ApJL, 822 2, L2, 2016) presented astrometric monitoring of the young exoplanet HD 95086 b obtained with GPI between 2013 and 2016. Efficient Monte Carlo techniques place preliminary constraints on the orbital parameters of HD 95086 b. Under the assumption of a coplanar planet-disk system, the periastron of HD 95086 b is beyond 51 AU. Therefore, HD 95086 b cannot carve the entire gap inferred from the measured infrared excess in the SED of HD 95086. Additional photometric and spectroscopic measurements reported by de Rosa et al. (2016, apJ, in press) showed that the spectral energy distribution of HD 95086 b is best fit by low temperature (T~800-1300 K), low surface gravity spectra from models which simulate high photospheric dust content. Its temperature is typical to L/T transition objects, but the spectral type is poorly constrained. HD 95086 b is an important exoplanet to test our models of atmospheric properties of young extrasolar planets.Direct detections of debris disk are keys to infer the collisional past and understand the formation of planetary systems. Two debris disks were recently studied with GPI:- Draper et al. (submitted to ApJ, 2016) show the resolved circumstellar debris disk around HD 111520 at a projected range of ~30-100 AU using both total and polarized H-band intensity. Structures in the disks such as a large brightness asymmetry and symmetric polarization fraction are seen. Additional data would confirm if a large disruption event from a stellar fly-by or planetary perturbations altered the disk density- Esposito et al. (submitted to ApJ, 2016) combined Keck NIRC2 data taken at 1.2-2.3 microns and GPI 1.6 micron total intensity and polarized light detections that probes down to projected separations less than 10 AU to show that the HD

  7. Law, Policy and Nonproliferation Project Events and Workshops: Key Themes, Results and Related Materials 2008 - 2009

    DTIC Science & Technology

    2010-04-01

    treaty negotiating process to fill gaps in the international legal regime in the field of WMD SECTION TWO: KEY THEMES LAW, POLICY AND...science behind identifying the source of fissile materials used in a nuclear detonation. The process involves identifying the radiological signature of...fissile materials, which varies depending on whether uranium or plutonium serves as the basis of the nuclear fuel, and what enrichment processes were

  8. Identifying Key Features of Effective Active Learning: The Effects of Writing and Peer Discussion

    ERIC Educational Resources Information Center

    Linton, Debra L.; Pangle, Wiline M.; Wyatt, Kevin H.; Powell, Karli N.; Sherwood, Rachel E.

    2014-01-01

    We investigated some of the key features of effective active learning by comparing the outcomes of three different methods of implementing active-learning exercises in a majors introductory biology course. Students completed activities in one of three treatments: discussion, writing, and discussion + writing. Treatments were rotated weekly between…

  9. Physically Active Adults: An Analysis of the Key Variables That Keep Them Moving

    ERIC Educational Resources Information Center

    Downs, Andrew

    2016-01-01

    Background: A large proportion of adults are insufficiently physically active, and researchers have yet to determine the factors that enable individuals to maintain adequate levels of physical activity throughout adulthood. Purpose: This study sought to identify the key variables linked with consistent physical activity in adulthood as elucidated…

  10. Mont Terri Underground Rock Laboratory, Switzerland-Research Program And Key Results

    NASA Astrophysics Data System (ADS)

    Nussbaum, C. O.; Bossart, P. J.

    2012-12-01

    Argillaceous formations generally act as aquitards because of their low hydraulic conductivities. This property, together with the large retention capacity of clays for cationic contaminants and the potential for self-sealing, has brought clay formations into focus as potential host rocks for the geological disposal of radioactive waste. Excavated in the Opalinus Clay formation, the Mont Terri underground rock laboratory in the Jura Mountains of NW Switzerland is an important international test site for researching clay formations. Research is carried out in the underground facility, which is located adjacent to the security gallery of the Mont Terri motorway tunnel. Fifteen partners from European countries, USA, Canada and Japan participate in the project. The objectives of the research program are to analyze the hydrogeological, geochemical and rock mechanical properties of the Opalinus Clay, to determine the changes induced by the excavation of galleries and by heating of the rock formation, to test sealing and container emplacement techniques and to evaluate and improve suitable investigation techniques. For the safety of deep geological disposal, it is of key importance to understand the processes occurring in the undisturbed argillaceous environment, as well as the processes in a disturbed system, during the operation of the repository. The objectives are related to: 1. Understanding processes and mechanisms in undisturbed clays and 2. Experiments related to repository-induced perturbations. Experiments of the first group are dedicated to: i) Improvement of drilling and excavation technologies and sampling methods; ii) Estimation of hydrogeological, rock mechanical and geochemical parameters of the undisturbed Opalinus Clay. Upscaling of parameters from laboratory to in situ scale; iii) Geochemistry of porewater and natural gases; evolution of porewater over time scales; iv) Assessment of long-term hydraulic transients associated with erosion and thermal

  11. [Results of 2 years of activity].

    PubMed

    Panigazzi, M

    2010-01-01

    Work-related injuries and occupational diseases are a scourge of modern, western societies, which, although technologically advanced, have difficulty in preventing, treating and rehabilitating victims with speed and efficiency. The current hospital neuromotor rehabilitation centres, whether public or accredited private structures, have notable difficulty in meeting the demand, which despite annual fluctuations and variable needs, does not, overall, seem to be decreasing. We present the results of an organization model developed at the "Fondazione Maugeri" Scientific Institute (Pavia, Italy), the criteria used for the activity, the technological innovations employed to determine ability, and the prospects for further development. This model is effective from a health care-rehabilitative point of view, also in the light of the new legislative scenarios, and is sustainable from an economic points of view; overall it is, therefore, efficient.

  12. Magnesium impacts myosin V motor activity by altering key conformational changes in the mechanochemical cycle.

    PubMed

    Trivedi, Darshan V; Muretta, Joseph M; Swenson, Anja M; Thomas, David D; Yengo, Christopher M

    2013-07-09

    We investigated how magnesium (Mg) impacts key conformational changes during the ADP binding/release steps in myosin V and how these alterations impact the actomyosin mechanochemical cycle. The conformation of the nucleotide binding pocket was examined with our established FRET system in which myosin V labeled with FlAsH in the upper 50 kDa domain participates in energy transfer with mant labeled nucleotides. We examined the maximum actin-activated ATPase activity of MV FlAsH at a range of free Mg concentrations (0.1-9 mM) and found that the highest activity occurs at low Mg (0.1-0.3 mM), while there is a 50-60% reduction in activity at high Mg (3-9 mM). The motor activity examined with the in vitro motility assay followed a similar Mg-dependence, and the trend was similar with dimeric myosin V. Transient kinetic FRET studies of mantdADP binding/release from actomyosin V FlAsH demonstrate that the transition between the weak and strong actomyosin.ADP states is coupled to movement of the upper 50 kDa domain and is dependent on Mg with the strong state stabilized by Mg. We find that the kinetics of the upper 50 kDa conformational change monitored by FRET correlates well with the ATPase and motility results over a wide range of Mg concentrations. Our results suggest the conformation of the upper 50 kDa domain is highly dynamic in the Mg free actomyosin.ADP state, which is in agreement with ADP binding being entropy driven in the absence of Mg. Overall, our results demonstrate that Mg is a key factor in coupling the nucleotide- and actin-binding regions. In addition, Mg concentrations in the physiological range can alter the structural transition that limits ADP dissociation from actomyosin V, which explains the impact of Mg on actin-activated ATPase activity and in vitro motility.

  13. Tellurium in active volcanic environments: Preliminary results

    NASA Astrophysics Data System (ADS)

    Milazzo, Silvia; Calabrese, Sergio; D'Alessandro, Walter; Brusca, Lorenzo; Bellomo, Sergio; Parello, Francesco

    2014-05-01

    Tellurium is a toxic metalloid and, according to the Goldschmidt classification, a chalcophile element. In the last years its commercial importance has considerably increased because of its wide use in solar cells, thermoelectric and electronic devices of the last generation. Despite such large use, scientific knowledge about volcanogenic tellurium is very poor. Few previous authors report result of tellurium concentrations in volcanic plume, among with other trace metals. They recognize this element as volatile, concluding that volcanic gases and sulfur deposits are usually enriched with tellurium. Here, we present some results on tellurium concentrations in volcanic emissions (plume, fumaroles, ash leachates) and in environmental matrices (soils and plants) affected by volcanic emissions and/or deposition. Samples were collected at Etna and Vulcano (Italy), Turrialba (Costa Rica), Miyakejima, Aso, Asama (Japan), Mutnovsky (Kamchatka) at the crater rims by using common filtration techniques for aerosols (polytetrafluoroethylene filters). Filters were both eluted with Millipore water and acid microwave digested, and analyzed by inductively coupled plasma mass spectrometry (ICP-MS). Volcanic ashes emitted during explosive events on Etna and Copahue (Argentina) were analyzed for tellurium bulk composition and after leaching experiments to evaluate the soluble fraction of tellurium. Soils and leaves of vegetation were also sampled close to active volcanic vents (Etna, Vulcano, Nisyros, Nyiragongo, Turrialba, Gorely and Masaya) and investigated for tellurium contents. Preliminary results showed very high enrichments of tellurium in volcanic emissions comparing with other volatile elements like mercury, arsenic, thallium and bismuth. This suggests a primary transport in the volatile phase, probably in gaseous form (as also suggested by recent studies) and/or as soluble salts (halides and/or sulfates) adsorbed on the surface of particulate particles and ashes. First

  14. Phosphatase activity in relation to key litter and soil properties in mature subtropical forests in China.

    PubMed

    Hou, Enqing; Chen, Chengrong; Wen, Dazhi; Liu, Xian

    2015-05-15

    Phosphatase-mediated phosphorus (P) mineralization is one of the critical processes in biogeochemical cycling of P and determines soil P availability in forest ecosystems; however, the regulation of soil phosphatase activity remains elusive. This study investigated the potential extracellular activities of acid phosphomonoesterase (AcPME) and phosphodiesterase (PDE) and how they were related to key edaphic properties in the L horizon (undecomposed litter) and F/H horizon (fermented and humified litter) and the underlying mineral soil at the 0-15cm depth in eight mature subtropical forests in China. AcPME activity decreased significantly in the order of F/H horizon>L horizon>mineral soil horizon, while the order for PDE activity was L horizon=F/H horizon>mineral soil horizon. AcPME (X axis) and PDE (Y axis) activities were positively correlated in all horizons with significantly higher slope in the L and F/H horizons than in the mineral soil horizon. Both AcPME and PDE activities were positively related to microbial biomass C, moisture content and water-holding capacity in the L horizon, and were positively related to soil C:P, N:P and C:N ratios and fine root (diameter≤2mm) biomass in the mineral soil horizon. Both enzyme activities were also interactively affected by forest and horizon, partly due to the interactive effect of forest and horizon on microbial biomass. Our results suggest that modulator(s) of the potential extracellular activity of phosphatases vary with horizon, depending on the relative C, P and water availability of the horizon.

  15. The SEDIBUD (Sediment Budgets in Cold Environments) Programme: Current activities and future key tasks

    NASA Astrophysics Data System (ADS)

    Beylich, A. A.; Lamoureux, S. F.; Decaulne, A.

    2012-04-01

    Projected climate change in cold regions is expected to alter melt season duration and intensity, along with the number of extreme rainfall events, total annual precipitation and the balance between snowfall and rainfall. Similarly, changes to the thermal balance are expected to reduce the extent of permafrost and seasonal ground frost and increase active layer depths. These effects will undoubtedly change surface environments in cold regions and alter the fluxes of sediments, nutrients and solutes, but the absence of quantitative data and coordinated process monitoring and analysis to understand the sensitivity of the Earth surface environment is acute in cold climate environments. The International Association of Geomorphologists (I.A.G./A.I.G.)SEDIBUD (Sediment Budgets in Cold Environments) Programme was formed in 2005 to address this existing key knowledge gap. SEDIBUD currently has about 400 members worldwide and the Steering Committee of this international programme is composed of ten scientists from eight different countries: Achim A. Beylich (Chair) (Norway), Armelle Decaulne (Secretary) (France), John C. Dixon (USA), Scott F. Lamoureux (Vice-Chair) (Canada), John F. Orwin (Canada), Jan-Christoph Otto (Austria), Irina Overeem (USA), Thorsteinn Saemundsson (Iceland), Jeff Warburton (UK), Zbigniew Zwolinski (Poland). The central research question of this global group of scientists is to: Assess and model the contemporary sedimentary fluxes in cold climates, with emphasis on both particulate and dissolved components. Initially formed as European Science Foundation (ESF) Network SEDIFLUX (2004-2006), SEDIBUD has further expanded to a global group of researchers with field research sites located in polar and alpine regions in the northern and southern hemisphere. Research carried out at each of the close to 50 defined SEDIBUD key test sites varies by programme, logistics and available resources, but typically represent interdisciplinary collaborations of

  16. Key Recent Scientific Results from the Opportunity Rover's Exploration of Cape Tribulation, Endeavour Crater, Mars

    NASA Astrophysics Data System (ADS)

    Arvidson, R. E.; Squyres, S. W.; Gellert, R.; Herkenhoff, K. E.; Mittlefehldt, D. W.; Crumpler, L. S.; McLennan, S. M.; Farrand, W. H.; Jolliff, B. L.; Morris, R. V.

    2015-12-01

    The Opportunity Rover is in its 11th year of exploration, currently exploring the Cape Tribulation rim segment of the ~22 km wide Noachian Endeavour Crater and its tilted and fractured outcrops. A key target for Opportunity's measurements has been the Spirit of Saint Louis crater (SoSL), which is ~25 m wide, oval in plan view, shallow, flat-floored, and has a slightly raised rim. SoSL crater is surrounded by an apron of bright, polygonally-shaped outcrops and is superimposed on a gentle swale in Cape Tribulation. Rocks in a thin reddish zone on the rim are enriched in hematite, Si, and Ge, and depleted in Fe, relative to surrounding rocks. Apron rocks include an outcrop also enriched in Si and Ge, and slightly depleted in Fe. In general rocks in the crater and apron have elevated S levels relative to Shoemaker formation breccias, tracking values observed in the Cook Haven (gentle swale superimposed on Murray Ridge and site of Opportunity's 5th winter site) and the Hueytown fracture (running perpendicular to Cape Tribulation) outcrops. SoSL crater lies just to the west of Marathon Valley, a key target for exploration by Opportunity because five separate CRISM observations indicate the presence of Fe/Mg smectites on the upper valley floor. Opportunity data show that low relief, relatively bright, wind-scoured outcrops dominate the valley floor where not covered by scree and soil shed from surrounding walls. Initial reconnaissance shows that the outcrops are breccias with compositions similar to the typical SoSL crater apron and floor rocks, although only the very upper portion of the valley has been explored as of August 2015. Pervasive but modest aqueous alteration of Endeavour's rim is implied by the combination of CRISM and Opportunity data, providing insight into early aqueous processes dominated in this location by relatively low water to rock ratios, and at least in part associated with enhanced fluid flow along fractures.

  17. KEY COMPARISON: Results of the key comparison CCM.FF-K4 for volume of liquids at 20 L and 100 mL

    NASA Astrophysics Data System (ADS)

    Arias, Roberto; Maldonado, Manuel; Wright, John; Jacques, Claude; Lachance, Christian; Lau, Peter; Többen, Helmut; Cignolo, Giorgio; Lorefice, Salvatore; Man, John; Aibe, Valter Y.

    2006-01-01

    A key comparison was performed in order to compare national measurement systems to determine volume of liquids, particularly at fixed volumes of 20 L and 100 mL. The participants were CENAM (Mexico), NIST (United States of America), NRC/MC (Canada), SP (Sweden), PTB (Germany), INRIM (former IMGC, Italy), NMIA (Australia) and INMETRO (Brazil). CENAM acted as pilot laboratory. The measurements were carried out from December 2003 to March 2005. The chosen values of volume (20 L and 100 mL) are both representatives of the Calibration and Measurement Capabilities (CMCs) declared by most of the participating national metrology institutes. The transfer standards (TSs) were three stainless steel pipettes for volume at 20 L and six commercially available glass pycnometers for volume at 100 mL. Prior to the beginning of the key comparison, the 20 L TSs were tested by CENAM, SP and NMIA The results of the test phase showed excellent values for both repeatability and reproducibility. During the CCM.FF-K4, the results of most of the laboratories showed good agreement with the reference values. The best estimation of the measurands, as reported by the participants showed a general agreement better than ±0.0025% for volume of liquids at 100 mL and 20 L. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

  18. Key Recent Scientific Results from the Opportunity Rover's Exploration of Endeavour Crater, Mars

    NASA Technical Reports Server (NTRS)

    Arvidson, R. E.; Squyres, S. W.; Gellert, R.; Herkenhoff, K.; Mittlefehldt, D.; Crumpler, L.; McLennan, S.; Farrand, W. H.; Joliff, B. L.; Morris, R. V.

    2015-01-01

    The Opportunity Rover is currently in its 11th year of operations, exploring the rim of the approximately 22 km wide Noachian-age Endeavour Crater. Opportunity spent its 5th winter season in Cook Haven, a gentle swale along Murray Ridge. Two small rocks serendipitously overturned by rover wheel motions show evidence for aqueous precipitation of sulfates, and interaction with a strong oxidant (e.g., O2) to form a thin, high valence state Mn oxide coating. After the winter, Opportunity headed south to Cape Tribulation and explored Shoemaker formation impact breccias, finding numerous Ca-sulfate veins cutting across outcrops. A key target for Opportunity's measurements has been the Spirit of Saint Louis crater (SoSL), which is approximately 25 m wide, oval in plan view, shallow, flat-floored, and has a slightly raised rim. SoSL crater is surrounded by an apron of bright, polygonally-shaped outcrops and is superimposed on a gentle swale in Cape Tribulation. Rocks in a thin reddish zone on the rim are enriched in hematite, Si, and Ge, and depleted in Fe, relative to surrounding rocks. Apron rocks include an outcrop also enriched in Si and Ge, and slightly depleted in Fe. In general rocks in the crater and apron have elevated S relative to Shoemaker formation breccias, tracking values observed in the Cook Haven and the Hueytown (fracture running perpendicular to Cape Tribulation) outcrops. SoSL crater lies just to the west of Marathon Valley, a key target for exploration by Opportunity because five separate CRISM observations indicate the presence of Fe/Mg smectites on the upper valley floor. Opportunity data show that low relief, relatively bright polygonal outcrops dominate the valley floor where not covered by scree and soil shed from surrounding walls. Initial reconnaissance shows that the outcrops are breccias with compositions similar to the typical SoSL crater apron and floor rocks, although only the very upper portion of the valley has been explored as of August

  19. The ClinicalTrials.gov Results Database — Update and Key Issues

    PubMed Central

    Zarin, Deborah A.; Tse, Tony; Williams, Rebecca J.; Califf, Robert M.; Ide, Nicholas C.

    2011-01-01

    BACKGROUND The ClinicalTrials.gov trial registry was expanded in 2008 to include a database for reporting summary results. We summarize the structure and contents of the results database, provide an update of relevant policies, and show how the data can be used to gain insight into the state of clinical research. METHODS We analyzed ClinicalTrials.gov data that were publicly available between September 2009 and September 2010. RESULTS As of September 27, 2010, ClinicalTrials.gov received approximately 330 new and 2000 revised registrations each week, along with 30 new and 80 revised results submissions. We characterized the 79,413 registry and 2178 results of trial records available as of September 2010. From a sample cohort of results records, 78 of 150 (52%) had associated publications within 2 years after posting. Of results records available publicly, 20% reported more than two primary outcome measures and 5% reported more than five. Of a sample of 100 registry record outcome measures, 61% lacked specificity in describing the metric used in the planned analysis. In a sample of 700 results records, the mean number of different analysis populations per study group was 2.5 (median, 1; range, 1 to 25). Of these trials, 24% reported results for 90% or less of their participants. CONCLUSIONS ClinicalTrials.gov provides access to study results not otherwise available to the public. Although the database allows examination of various aspects of ongoing and completed clinical trials, its ultimate usefulness depends on the research community to submit accurate, informative data. PMID:21366476

  20. Overview of Key Results from the Exploration of the Pluto System by New Horizons

    NASA Astrophysics Data System (ADS)

    Stern, S. A.; Weaver, H. A., Jr.; Young, L. A.; Olkin, C.; Ennico Smith, K.; Moore, J. M.; Spencer, J. R.; McKinnon, W. B.; Grundy, W. M.; Cruikshank, D. P.; Bagenal, F.; Gladstone, R.; Summers, M. E.

    2015-12-01

    Pluto and its satellites were explored by NASA's New Horizons spacecraft in 2015, with closest approach to Pluto on 14 July 2015. Pluto's surface is found to be remarkably diverse in terms of its range of landforms, terrain ages, and albedo, color, and composition gradients. Strong evidence was found for geologically young surface units, a water-ice crust, ice convection, and glacial flow. Pluto's wide range of surface expressions and long term activity raise fundamental questions about how small planets can have active processes billions of years after their formation. Pluto's atmosphere was found to be more extended than anticipated, to have an extensive global haze layer, several new trace species, and a low surface pressure of ~10 microbars. Pluto's large satellite Charon's surface geology is also diverse, displaying tectonics and evidence for a heterogeneous crustal composition; Charon's north pole displays puzzling dark terrain; no evidence for a Charon atmosphere has been found. Sizes and reflectivities for all four of Pluto's small satellites will be reported. Despite much improved diameter limits, no new satellites of Pluto were detected by New Horizons. In this review talk I will summarize these and other findings about the Pluto system.

  1. Key clinical activities for quality asthma care. Recommendations of the National Asthma Education and Prevention Program.

    PubMed

    Williams, Seymour G; Schmidt, Diana K; Redd, Stephen C; Storms, William

    2003-03-28

    In 1997, the National Asthma Education and Prevention Program (NAEPP), coordinated by the National Heart, Lung, and Blood Institute, published the second Expert Panel Report (EPR-2): Guidelines for the Diagnosis and Management of Asthma (National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. Expert Panel Report 2: Guidelines for the diagnosis and management of asthma. Bethesda MD: US Department of Health and Human Services, National Institutes of Health, 1997; publication no. 97-4051. Available at http://www.nhlbi.nih.gov/guidelines/ asthma/asthgdln.pdf). Subsequently, the NAEPP Expert Panel identified key questions regarding asthma management that were submitted to an evidence practice center of the Agency for Healthcare Research and Quality to conduct a systematic review of the evidence. The resulting evidence report was used by the Expert Panel to update recommendations for clinical practice on selected topics. These recommendations (EPR-Update 2002) were published in 2002. (National Heart, Lung, and Blood Institute, National Asthma Education and Prevention Program. Guidelines for the diagnosis and management of asthma--update on selected topics 2002. J Allergy Clin Immunol 2002;110[November 2002, part 2]. Available at http://www.nhlbi.nih.gov/guidelines/asthma/index.htm). To improve the implementation of these guidelines, a working group of the Professional Education Subcommittee of the NAEPP extracted key clinical activities that should be considered as essential for quality asthma care in accordance with the EPR-2 guidelines and the EPR-Update 2002. The purpose was to develop a report that would help purchasers and planners of health care define the activities that are important to quality asthma care, particularly in reducing symptoms and preventing exacerbations, and subsequently reducing the overall national burden of illness and death from asthma. This report is intended to help employer health benefits managers and

  2. The Key Role of Sulfation and Branching on Fucoidan Antitumor Activity.

    PubMed

    Oliveira, Catarina; Ferreira, Andreia S; Novoa-Carballal, Ramon; Nunes, Cláudia; Pashkuleva, Iva; Neves, Nuno M; Coimbra, Manuel A; Reis, Rui L; Martins, Albino; Silva, Tiago H

    2016-12-20

    There is an urgent need for antitumor bioactive agents with minimal or no side effects over normal adjacent cells. Fucoidan is a marine-origin polymer with known antitumor activity. However, there are still some concerns about its application due to the inconsistent experimental results, specifically its toxicity over normal cells and the mechanism behind its action. Herein, three fucoidan extracts (FEs) have been tested over normal and breast cancer cell lines. From cytotoxicity results, only one of the extracts shows selective antitumor behavior (at 0.2 mg mL(-1) ), despite similarities in sulfation degree and carbohydrates composition. Although the three FEs present different molecular weights, depolymerization of selected samples discarded Mw as the key factor in the antitumor activity. Significant differences in sulfates position and branching are observed, presenting FE 2 the higher branching degree. Based on all these experimental data, it is believed that these last two properties are the ones that influence the cytotoxic effects of fucoidan extracts.

  3. Key results of battery performance and life tests at Argonne National Laboratory

    NASA Astrophysics Data System (ADS)

    Deluca, W. H.; Gillie, K. R.; Kulaga, J. E.; Smaga, J. A.; Tummillo, A. F.; Webster, C. E.

    1991-12-01

    Advanced battery technology evaluations are performed under simulated electric vehicle operating conditions at Argonne National Laboratory's & Diagnostic Laboratory (ADL). The ADL provide a common basis for both performance characterization and life evaluation with unbiased application of tests and analyses. This paper summarizes the performance characterizations and life evaluations conducted in 1991 on twelve single cells and eight 3- to 360-cell modules that encompass six battery technologies (Na/S, Li/MS, Ni/MH, Zn/Br, Ni/Fe, and Pb-Acid). These evaluations were performed for the Department of Energy, Office of Transportation Technologies, Electric and Hybrid Propulsion Division. The results measure progress in battery R & D programs, compare battery technologies, and provide basic data for modeling and continuing R & D to battery users, developers, and program managers.

  4. Key results of battery performance and life tests at Argonne National Laboratory

    SciTech Connect

    DeLuca, W.H.; Gillie, K.R.; Kulaga, J.E.; Smaga, J.A.; Tummillo, A.F.; Webster, C.E.

    1991-12-31

    Advanced battery technology evaluations are performed under simulated electric vehicle operating conditions at Argonne National Laboratory`s & Diagnostic Laboratory (ADL). The ADL provide a common basis for both performance characterization and life evaluation with unbiased application of tests and analyses. This paper summarizes the performance characterizations and life evaluations conducted in 1991 on twelve single cells and eight 3- to 360-cell modules that encompass six battery technologies (Na/S, Li/MS, Ni/MH, Zn/Br, Ni/Fe, and Pb-Acid). These evaluations were performed for the Department of Energy, Office of Transportation Technologies, Electric and Hybrid Propulsion Division. The results measure progress in battery R & D programs, compare battery technologies, and provide basic data for modeling and continuing R & D to battery users, developers, and program managers.

  5. Key results of battery performance and life tests at Argonne National Laboratory

    SciTech Connect

    DeLuca, W.H.; Gillie, K.R.; Kulaga, J.E.; Smaga, J.A.; Tummillo, A.F.; Webster, C.E.

    1991-01-01

    Advanced battery technology evaluations are performed under simulated electric vehicle operating conditions at Argonne National Laboratory's Diagnostic Laboratory (ADL). The ADL provide a common basis for both performance characterization and life evaluation with unbiased application of tests and analyses. This paper summarizes the performance characterizations and life evaluations conducted in 1991 on twelve single cells and eight 3- to 360-cell modules that encompass six battery technologies (Na/S, Li/MS, Ni/MH, Zn/Br, Ni/Fe, and Pb-Acid). These evaluations were performed for the Department of Energy, Office of Transportation Technologies, Electric and Hybrid Propulsion Division. The results measure progress in battery R D programs, compare battery technologies, and provide basic data for modeling and continuing R D to battery users, developers, and program managers.

  6. Canine leishmaniasis: the key points for qPCR result interpretation

    PubMed Central

    2011-01-01

    Background Diagnosis and follow up of CanL is difficult since the range of clinical signs is varied and seroprevalence is high in endemic areas. The aims of this study were: i) demonstrate the advantages of Leishmania qPCR to diagnose and control CanL and highlight its prognostic value and ii) propose guidelines for tissue selection and infection monitoring. Findings This study included 710 dogs living in an endemic area of leishmaniasis. Forty percent (285/710) exhibited clinical signs consistent with CanL. Infection was detected in 36.3% (258/710) of the dogs of which 4.5% (32/710) were detected by qPCR, 16.2% (115/710) detected by ELISA and 15.6% (111/710) tested positive for both tests. Only 17.9% (127/710) of the dogs were classified sick (affected) with CanL. All symptomatic dogs with medium or high ELISA titers were qPCR-positive in blood samples. All dogs with inconclusive or low ELISA results with high or medium qPCR parasitemia values developed the disease. Seventy one percent of asymptomatic ELISA-positive dogs confirmed by qPCR (medium to high parasitemia) developed the disease. Bone marrow or lymph node aspirate should be selected to ensure the absence of the parasite in asymptomatic dogs: 100-1,000 parasites/ml in bone marrow are detectable in blood, whereas lower parasite loads are usually negative. Almost 10% of negative samples in blood were positive in conjunctival swabs. Conclusions Because qPCR allows parasite quantification, it is an effective tool to confirm a diagnosis of CanL in (i) cases of inconclusive ELISA results, (ii) when the dog has not yet seroconverted, or (iii) for treatment monitoring. PMID:21489253

  7. Sustained impact of community-based physical activity interventions: key elements for success

    PubMed Central

    2013-01-01

    Background Compelling evidence supports the cost effectiveness and potential impact of physical activity on chronic disease prevention and health promotion. Quality of evidence is one piece, but certainly not the sole determinant of whether public health interventions, physical activity focused or otherwise, achieve their full potential for impact. Health promotion at both population and community levels must progress beyond health intervention models that isolate individuals from social, environmental, and political systems of influence. We offer a critical evaluation of lessons learned from two successful research initiatives to provide insights as to how health promotion research contributes to sustained impact. We highlight factors key to success including the theoretical and methodological integration of: i) a social ecological approach; ii) participatory action research (PAR) methods; and iii) an interdisciplinary team. Methods To identify and illustrate the key elements of our success we layered an evaluation of steps taken atop a review of relevant literature. Results In the school-based case study (Action Schools! BC), the success of our approach included early and sustained engagement with a broad cross-section of stakeholders, establishing partnerships across sectors and at different levels of government, and team members across multiple disciplines. In the neighbourhood built environment case study, the three domains guided our approach through study design and team development, and the integration of older adults’ perspectives into greenway design plans. In each case study we describe how elements of the domains serve as a guide for our work. Conclusion To sustain and maximize the impact of community-based public health interventions we propose the integration of elements from three domains of research that acknowledge the interplay between social, environmental and poilitical systems of influence. We emphasize that a number of key factors determine

  8. Standardization activities for harmonization of test results.

    PubMed

    Dati, F; Brand, B

    2000-07-01

    In the last years the search for sensitive and specific markers of renal damage and/or renal function has conducted to the development of laboratory assays for measurement of urinary proteins such as albumin, beta(2)-microglobulin, alpha(1)-microglobulin, cystatin C, etc. Furthermore, there have been new applications of already known markers based on different, reformulated methods which often rely on more advanced technologies. It is evident that such developments are connected with analytical and interpretative problems for laboratory managers and clinicians. In this situation, it is essential that international societies develop comprehensive measures for the quality management of these assays and issue uniform and carefully elaborated guidelines to ensure optimal test utilization. International activities are also directed to the development of optimized and standardized methods as well as to the production and evaluation of appropriate reference materials and, finally, to the establishment of appropriate reference ranges and cut-off values for specific analytes. The main use of reference materials is in the transfer of their accurately assigned values to the calibrators of diagnostic companies for calibration of commercially available test systems. These international standardization activities and strategies will allow a harmonized approach to disease management using a more reliable laboratory testing based on quality and value.

  9. Direct transcriptional activation of BT genes by NLP transcription factors is a key component of the nitrate response in Arabidopsis.

    PubMed

    Sato, Takeo; Maekawa, Shugo; Konishi, Mineko; Yoshioka, Nozomi; Sasaki, Yuki; Maeda, Haruna; Ishida, Tetsuya; Kato, Yuki; Yamaguchi, Junji; Yanagisawa, Shuichi

    2017-01-29

    Nitrate modulates growth and development, functioning as a nutrient signal in plants. Although many changes in physiological processes in response to nitrate have been well characterized as nitrate responses, the molecular mechanisms underlying the nitrate response are not yet fully understood. Here, we show that NLP transcription factors, which are key regulators of the nitrate response, directly activate the nitrate-inducible expression of BT1 and BT2 encoding putative scaffold proteins with a plant-specific domain structure in Arabidopsis. Interestingly, the 35S promoter-driven expression of BT2 partially rescued growth inhibition caused by reductions in NLP activity in Arabidopsis. Furthermore, simultaneous disruption of BT1 and BT2 affected nitrate-dependent lateral root development. These results suggest that direct activation of BT1 and BT2 by NLP transcriptional activators is a key component of the molecular mechanism underlying the nitrate response in Arabidopsis.

  10. 5 CFR 591.241 - What are the key activities of the COLA Advisory Committees?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... SERVICE REGULATIONS ALLOWANCES AND DIFFERENTIALS Cost-of-Living Allowance and Post Differential-Nonforeign Areas Program Administration § 591.241 What are the key activities of the COLA Advisory Committees? (a) The COLA Advisory Committees may— (1) Advise and assist OPM in planning living-cost surveys;...

  11. Determining barriers to creating an enabling environment in Cambodia: results from a baseline study with key populations and police

    PubMed Central

    Schneiders, Mira L; Weissman, Amy

    2016-01-01

    Introduction Cambodian law enforcement's limited acceptance of harm reduction has hindered HIV program effectiveness. With funding from the Australian Department of Foreign Affairs and Trade, FHI 360 supported the Ministry of Interior to implement the Police Community Partnership Initiative (PCPI) in Cambodia's capital Phnom Penh. To guide this, FHI 360 conducted a baseline study examining police and key populations’ attitudes and practices towards one another, including fear and occurrence of arrest. Methods Between December 2012 and January 2013, a cross-sectional survey of 199 police post officers, 199 people who use drugs (PWUD) including people who inject drugs (PWID), 199 men who have sex with men (MSM), 200 transgender women (TGW) and 200 female entertainment workers (FEW) was conducted in five Phnom Penh districts. Eligible participants were ≥18 years, members of a key population from selected hotspots or police officers, deputy chiefs or chiefs. Results Key populations’ median age was 25 years (IQR: 22–30); 40% had completed only primary school. Police were male (99.5%), with median age 43 years (IQR: 30 to 47), and 45 and 25% high school and university completion rates, respectively. Key populations feared arrest for carrying needles and syringes (67%), condoms (23%) and 19% felt afraid to access health services. Close to 75% of police reported body searching and 58% arresting key populations in the past six months for using drugs (64%), selling or distributing drugs (36%) or being violent (13%). Self-reported arrests (23% PWUD, 6% MSM, 6% TGW, 12% FEW; p<0.05), being verbally threatened (45% PWUD, 21% MSM, 25% TGW, 27% FEW; p<0.001) and body searched (44% PWUD, 28% MSM, 23% TGW, 8% FEW; p<0.001) was significantly higher among PWUD than other key populations. The majority (94%) of police believed arrest was an appropriate solution to reduce HIV and drug use and reported selling sex (88%) and carrying needles and syringes (55%) as valid reasons for

  12. Autocrine abscisic acid plays a key role in quartz-induced macrophage activation.

    PubMed

    Magnone, Mirko; Sturla, Laura; Jacchetti, Emanuela; Scarfì, Sonia; Bruzzone, Santina; Usai, Cesare; Guida, Lucrezia; Salis, Annalisa; Damonte, Gianluca; De Flora, Antonio; Zocchi, Elena

    2012-03-01

    Inhalation of quartz induces silicosis, a lung disease where alveolar macrophages release inflammatory mediators, including prostaglandin-E(2) (PGE(2)) and tumor necrosis factor α (TNF-α). Here we report the pivotal role of abscisic acid (ABA), a recently discovered human inflammatory hormone, in silica-induced activation of murine RAW264.7 macrophages and of rat alveolar macrophages (AMs). Stimulation of both RAW264.7 cells and AMs with quartz induced a significant increase of ABA release (5- and 10-fold, respectively), compared to untreated cells. In RAW264.7 cells, autocrine ABA released after quartz stimulation sequentially activates the plasma membrane receptor LANCL2 and NADPH oxidase, generating a Ca(2+) influx resulting in NFκ B nuclear translocation and PGE(2) and TNF-α release (3-, 2-, and 3.5-fold increase, respectively, compared to control, unstimulated cells). Quartz-stimulated RAW264.7 cells silenced for LANCL2 or preincubated with a monoclonal antibody against ABA show an almost complete inhibition of NFκ B nuclear translocation and PGE(2) and TNF-α release compared to controls electroporated with a scramble oligonucleotide or preincubated with an unrelated antibody. AMs showed similar early and late ABA-induced responses as RAW264.7 cells. These findings identify ABA and LANCL2 as key mediators in quartz-induced inflammation, providing possible new targets for antisilicotic therapy.

  13. Sublethal Effects of Insecticide Exposure on Megacopta cribraria (Fabricius) Nymphs: Key Biological Traits and Acetylcholinesterase Activity

    PubMed Central

    Miao, Jin; Reisig, Dominic D.; Li, Guoping; Wu, Yuqing

    2016-01-01

    Megacopta cribraria F. (Hemiptera: Plataspidae), the kudzu bug, is an invasive insect pest of U.S. soybean. At present, insecticide application is the primary and most effective control option for M. cribraria. In this study, the potential effects of sublethal and low-lethal concentrations (LC10 and LC40) of three common insecticides on key biological traits and acetylcholinesterase (AChE) activity of the treated nymphal stage of insect were assessed. The results show that the sublethal concentration of imidacloprid significantly reduced adult emergence rate of M. cribraria. A low-lethal concentration of imidacloprid significantly increased nymphal development time, but significantly decreased adult emergence rate and adult longevity. Both sublethal and low-lethal concentrations of acephate caused an increase in nymphal development time and a reduction in adult emergence rate and adult longevity. Fecundity of females was significantly reduced only by exposure to low-lethal concentrations of acephate. Sublethal and low-lethal concentrations of bifenthrin increased nymphal development time, but significantly decreased adult emergence rate. In addition, we found that the AChE activity of M. cribraria was significantly increased only by LC40 imidacloprid, but strongly inhibited by acephate. PMID:27638957

  14. Adenosine monophosphate-activated kinase and its key role in catabolism: structure, regulation, biological activity, and pharmacological activation.

    PubMed

    Krishan, Sukriti; Richardson, Des R; Sahni, Sumit

    2015-01-01

    Adenosine monophosphate-activated protein kinase (AMPK) is a cellular energy sensor, which once activated, plays a role in several processes within the cell to restore energy homeostasis. The protein enhances catabolic pathways, such as β-oxidation and autophagy, to generate ATP, and inhibits anabolic processes that require energy, including fatty acid, cholesterol, and protein synthesis. Due to its key role in the regulation of critical cellular pathways, deregulation of AMPK is associated with the pathology of many diseases, including cancer, Wolff-Parkinson-White syndrome, neurodegenerative disorders, diabetes, and metabolic syndrome. In fact, AMPK is a target of some pharmacological agents implemented in the treatment of diabetes (metformin and thiazolidinediones) as well as other naturally derived products, such as berberine, which is used in traditional medicine. Due to its critical role in the cell and the pathology of several disorders, research into developing AMPK as a therapeutic target is becoming a burgeoning and exciting field of pharmacological research. A profound understanding of the regulation and activity of AMPK would enhance its development as a promising therapeutic target.

  15. Prediction of Geomagnetic Activity and Key Parameters in High-Latitude Ionosphere-Basic Elements

    NASA Technical Reports Server (NTRS)

    Lyatsky, W.; Khazanov, G. V.

    2007-01-01

    Prediction of geomagnetic activity and related events in the Earth's magnetosphere and ionosphere is an important task of the Space Weather program. Prediction reliability is dependent on the prediction method and elements included in the prediction scheme. Two main elements are a suitable geomagnetic activity index and coupling function -- the combination of solar wind parameters providing the best correlation between upstream solar wind data and geomagnetic activity. The appropriate choice of these two elements is imperative for any reliable prediction model. The purpose of this work was to elaborate on these two elements -- the appropriate geomagnetic activity index and the coupling function -- and investigate the opportunity to improve the reliability of the prediction of geomagnetic activity and other events in the Earth's magnetosphere. The new polar magnetic index of geomagnetic activity and the new version of the coupling function lead to a significant increase in the reliability of predicting the geomagnetic activity and some key parameters, such as cross-polar cap voltage and total Joule heating in high-latitude ionosphere, which play a very important role in the development of geomagnetic and other activity in the Earth s magnetosphere, and are widely used as key input parameters in modeling magnetospheric, ionospheric, and thermospheric processes.

  16. Hydrogenosome Metabolism Is the Key Target for Antiparasitic Activity of Resveratrol against Trichomonas vaginalis

    PubMed Central

    Mallo, Natalia; Lamas, Jesús

    2013-01-01

    Metronidazole (MDZ) and related 5-nitroimidazoles are the recommended drugs for treatment of trichomoniasis, a sexually transmitted disease caused by the protozoan parasite Trichomonas vaginalis. However, novel treatment options are needed, as recent reports have claimed resistance to these drugs in T. vaginalis isolates. In this study, we analyzed for the first time the in vitro effects of the natural polyphenol resveratrol (RESV) on T. vaginalis. At concentrations of between 25 and 100 μM, RESV inhibited the in vitro growth of T. vaginalis trophozoites; doses of 25 μM exerted a cytostatic effect, and higher doses exerted a cytotoxic effect. At these concentrations, RESV caused inhibition of the specific activity of a 120-kDa [Fe]-hydrogenase (Tvhyd). RESV did not affect Tvhyd gene expression and upregulated pyruvate-ferredoxin oxidoreductase (a hydrogenosomal enzyme) gene expression only at a high dose (100 μM). At doses of 50 to 100 μM, RESV also caused overexpression of heat shock protein 70 (Hsp70), a protective protein found in the hydrogenosome of T. vaginalis. The results demonstrate the potential of RESV as an antiparasitic treatment for trichomoniasis and suggest that the mechanism of action involves induction of hydrogenosomal dysfunction. In view of the results, we propose hydrogenosomal metabolism as a key target in the design of novel antiparasitic drugs. PMID:23478970

  17. Hydrogenosome metabolism is the key target for antiparasitic activity of resveratrol against Trichomonas vaginalis.

    PubMed

    Mallo, Natalia; Lamas, Jesús; Leiro, José M

    2013-06-01

    Metronidazole (MDZ) and related 5-nitroimidazoles are the recommended drugs for treatment of trichomoniasis, a sexually transmitted disease caused by the protozoan parasite Trichomonas vaginalis. However, novel treatment options are needed, as recent reports have claimed resistance to these drugs in T. vaginalis isolates. In this study, we analyzed for the first time the in vitro effects of the natural polyphenol resveratrol (RESV) on T. vaginalis. At concentrations of between 25 and 100 μM, RESV inhibited the in vitro growth of T. vaginalis trophozoites; doses of 25 μM exerted a cytostatic effect, and higher doses exerted a cytotoxic effect. At these concentrations, RESV caused inhibition of the specific activity of a 120-kDa [Fe]-hydrogenase (Tvhyd). RESV did not affect Tvhyd gene expression and upregulated pyruvate-ferredoxin oxidoreductase (a hydrogenosomal enzyme) gene expression only at a high dose (100 μM). At doses of 50 to 100 μM, RESV also caused overexpression of heat shock protein 70 (Hsp70), a protective protein found in the hydrogenosome of T. vaginalis. The results demonstrate the potential of RESV as an antiparasitic treatment for trichomoniasis and suggest that the mechanism of action involves induction of hydrogenosomal dysfunction. In view of the results, we propose hydrogenosomal metabolism as a key target in the design of novel antiparasitic drugs.

  18. Diagnosing Key Drivers of Job Impact and Business Results Attributable to Training at the Defense Acquisition University

    DTIC Science & Technology

    2011-10-01

    Management Science , 33(6), 687–705. Wold , H. (1975). Path models with latent variables: The NIPALS approach. In H. M. Blalock, A. Aganbegian, F. M...developed by Wold (1975), and it focuses on maximizing the Diagnosing Key Drivers of Job impact and Business Results October 2011 Attributable to Training...perfectly would have an R2 value of 100 percent, although this situation is virtually impossible to achieve in social science research. To put this

  19. Maintenance of a health promotion program in elementary schools: results from the CATCH-ON study key informant interviews.

    PubMed

    Lytle, Leslie A; Ward, Jerri; Nader, Phillip R; Pedersen, Sheryl; Williston, B J

    2003-08-01

    To better understand the institutionalization process in Child and Adolescent Trial for Cardiovascular Health (CATCH) intervention and control schools, 199 key informant interviews were conducted with school food service staff, physical education teachers, classroom teachers, and administrators at the four CATCH-ON field centers. School personnel were asked to talk about the degree of CATCH program implementation, who at the school or school district was instrumental in promoting CATCH, and the conditions that facilitated or impeded the institutionalization of CATCH activities and philosophies. The CATCH Physical Education (PE) component appeared to have the highest level of institutionalization, and the CATCH classroom curriculum and family components appeared to have the lowest levels of institutionalization. The primary barriers expressed included the low priority for health promotion activities and time constraints of schools: lack of mechanisms for training of school staff; and lack of sufficient funds for materials, equipment, and lower fat vendor products.

  20. Identification of guanine exchange factor key residues involved in exchange activity and Ras interaction.

    PubMed

    Camus, C; Hermann-Le Denmat, S; Jacquet, M

    1995-09-07

    We have carried out a functional analysis of the human HGRF55 exchange factor in the yeast Saccharomyces cerevisiae. Twelve residues conserved among most of all known guanine exchange factors (GEFs) have been independently changed to alanine. Taking advantage of the ability of Hgrf55p to replace the yeast Cdc25p exchange factor, and using the two-hybrid system with RAS2ala22 allele, we have identified key residues for the interaction with Ras and/or its activation. Substitution of arginine 392 to alanine leads to a complete loss of interaction with Ras, though the protein remains stable. Substitution of Asp266 or Arg359 to alanine results in inactive proteins at 39 degrees C, still able however to interact with Ras. The other charged-to-alanine substitutions led to no detectable phenotype when present alone but most of them dramatically increased the temperature sensitive phenotype observed with [Asp266Ala] substitution. Surprisingly, the cysteine to alanine substitution in the highly conserved PCVPF/Y motif proved to be without effect, suggesting that the sulfhydryl group is not essential for stability or interaction with Ras.

  1. Regulation of sucrose metabolism in higher plants: localization and regulation of activity of key enzymes

    NASA Technical Reports Server (NTRS)

    Winter, H.; Huber, S. C.; Brown, C. S. (Principal Investigator)

    2000-01-01

    Sucrose (Suc) plays a central role in plant growth and development. It is a major end product of photosynthesis and functions as a primary transport sugar and in some cases as a direct or indirect regulator of gene expression. Research during the last 2 decades has identified the pathways involved and which enzymes contribute to the control of flux. Availability of metabolites for Suc synthesis and 'demand' for products of sucrose degradation are important factors, but this review specifically focuses on the biosynthetic enzyme sucrose-phosphate synthase (SPS), and the degradative enzymes, sucrose synthase (SuSy), and the invertases. Recent progress has included the cloning of genes encoding these enzymes and the elucidation of posttranslational regulatory mechanisms. Protein phosphorylation is emerging as an important mechanism controlling SPS activity in response to various environmental and endogenous signals. In terms of Suc degradation, invertase-catalyzed hydrolysis generally has been associated with cell expansion, whereas SuSy-catalyzed metabolism has been linked with biosynthetic processes (e.g., cell wall or storage products). Recent results indicate that SuSy may be localized in multiple cellular compartments: (1) as a soluble enzyme in the cytosol (as traditionally assumed); (2) associated with the plasma membrane; and (3) associated with the actin cytoskeleton. Phosphorylation of SuSy has been shown to occur and may be one of the factors controlling localization of the enzyme. The purpose of this review is to summarize some of the recent developments relating to regulation of activity and localization of key enzymes involved in sucrose metabolism in plants.

  2. Biological activity in Technosols as a key factor of their structure

    NASA Astrophysics Data System (ADS)

    Watteau, Françoise; Villemin, Geneviève; Bouchard, Adeline; Monserié, Marie-France; Séré, Geoffroy; Schwartz, Christophe; Morel, Jean-Louis

    2010-05-01

    The studies of the dynamics of organic matters within soils, show that their structural stability depends on the biological activity bound to the degradation of organic products. We wondered what it was for Technosols there. We then tried to specify the contribution of this biological activity to the structure of three contrasted technosols : - Technosol 1: a material originated from a former steel industry containing steel and coke residues, which was deposited two years ago in lysimetric plots - Technosol 2: a constructed soil (30 months) resulting from the combination of paper-mill sludge, thermally treated soil material excavated from a former coking plant site, and green-waste compost - Technosol 3: 30 years old technosol developed on flotation ponds of a former steel mill with strong metallic pollution, on which grows a forest ecosystem If these 3 technosols presented initially a similar organic carbon content (around 70 g.kg-1), the origin of organic matters was different A follow-up of the structural stability of these 3 systems, based on techniques of granulometric soil fractionation and morphological/analytical characterization at ultrastructural scale (TEM/EDX), was realized. Results showed the specific contribution of organic matters to the formation of stable organo-mineral associations, in particular those belonging to (0-50 μm) fraction. They mainly involved organic matter from vegetal origin coming from the spontaneous colonization of these 3 sites, but also from microbial origin corresponding to rhizospheric bacteria producing exopolymers. Organic matters from the compost and cellulosic fibers from the paper-mill sludge also contributed to the formation of organo-mineral associations all the more that compost was also a source of microorganisms. Organic matters were also associated to pollutant metallic elements (Pb, Zn, Mn) initially brought by the materials, then highlighting their possible transfer and questioning about their (bio

  3. Roles of key active-site residues in flavocytochrome P450 BM3.

    PubMed Central

    Noble, M A; Miles, C S; Chapman, S K; Lysek, D A; MacKay, A C; Reid, G A; Hanzlik, R P; Munro, A W

    1999-01-01

    The effects of mutation of key active-site residues (Arg-47, Tyr-51, Phe-42 and Phe-87) in Bacillus megaterium flavocytochrome P450 BM3 were investigated. Kinetic studies on the oxidation of laurate and arachidonate showed that the side chain of Arg-47 contributes more significantly to stabilization of the fatty acid carboxylate than does that of Tyr-51 (kinetic parameters for oxidation of laurate: R47A mutant, Km 859 microM, kcat 3960 min-1; Y51F mutant, Km 432 microM, kcat 6140 min-1; wild-type, Km 288 microM, kcat 5140 min-1). A slightly increased kcat for the Y51F-catalysed oxidation of laurate is probably due to decreased activation energy (DeltaG) resulting from a smaller DeltaG of substrate binding. The side chain of Phe-42 acts as a phenyl 'cap' over the mouth of the substrate-binding channel. With mutant F42A, Km is massively increased and kcat is decreased for oxidation of both laurate (Km 2. 08 mM, kcat 2450 min-1) and arachidonate (Km 34.9 microM, kcat 14620 min-1; compared with values of 4.7 microM and 17100 min-1 respectively for wild-type). Amino acid Phe-87 is critical for efficient catalysis. Mutants F87G and F87Y not only exhibit increased Km and decreased kcat values for fatty acid oxidation, but also undergo an irreversible conversion process from a 'fast' to a 'slow' rate of substrate turnover [for F87G (F87Y)-catalysed laurate oxidation: kcat 'fast', 760 (1620) min-1; kcat 'slow', 48.0 (44.6) min-1; kconv (rate of conversion from fast to slow form), 4.9 (23.8) min-1]. All mutants showed less than 10% uncoupling of NADPH oxidation from fatty acid oxidation. The rate of FMN-to-haem electron transfer was shown to become rate-limiting in all mutants analysed. For wild-type P450 BM3, the rate of FMN-to-haem electron transfer (8340 min-1) is twice the steady-state rate of oxidation (4100 min-1), indicating that other steps contribute to rate limitation. Active-site structures of the mutants were probed with the inhibitors 12-(imidazolyl

  4. Identification of Key Residues Determining Isomerohydrolase Activity of Human RPE65*

    PubMed Central

    Takahashi, Yusuke; Moiseyev, Gennadiy; Ma, Jian-xing

    2014-01-01

    RPE65 is the retinoid isomerohydrolase that converts all-trans-retinyl ester to 11-cis-retinol, a key reaction in the retinoid visual cycle. We have previously reported that cone-dominant chicken RPE65 (cRPE65) shares 90% sequence identity with human RPE65 (hRPE65) but exhibits substantially higher isomerohydrolase activity than that of bovine RPE65 or hRPE65. In this study, we sought to identify key residues responsible for the higher enzymatic activity of cRPE65. Based on the amino acid sequence comparison of mammalian and other lower vertebrates' RPE65, including cone-dominant chicken, 8 residues of hRPE65 were separately replaced by their counterparts of cRPE65 using site-directed mutagenesis. The enzymatic activities of cRPE65, hRPE65, and its mutants were measured by in vitro isomerohydrolase activity assay, and the retinoid products were analyzed by HPLC. Among the mutants analyzed, two single point mutants, N170K and K297G, and a double mutant, N170K/K297G, of hRPE65 exhibited significantly higher catalytic activity than WT hRPE65. Further, when an amino-terminal fragment (Met1–Arg33) of the N170K/K297G double mutant of hRPE65 was replaced with the corresponding cRPE65 fragment, the isomerohydrolase activity was further increased to a level similar to that of cRPE65. This finding contributes to the understanding of the structural basis for isomerohydrolase activity. This highly efficient human isomerohydrolase mutant can be used to improve the efficacy of RPE65 gene therapy for retinal degeneration caused by RPE65 mutations. PMID:25112876

  5. Key factor in rice husk ash/CaO sorbent for high flue gas desulfurization activity

    SciTech Connect

    Irvan Dahlan; Keat Teong Lee; Azlina Harun Kamaruddin; Abdul Rahman Mohamed

    2006-10-01

    Siliceous materials such as rice husk ash (RHA) have potential to be utilized as high performance sorbents for the flue gas desulfurization process in small-scale industrial boilers. This study presents findings on identifying the key factor for high desulfurization activity in sorbents prepared from RHA. Initially, a systematic approach using central composite rotatable design was used to develop a mathematical model that correlates the sorbent preparation variables to the desulfurization activity of the sorbent. The sorbent preparation variables studied are hydration period, x{sub 1} (6-16 h), amount of RHA, x{sub 2} (5-15 g), amount of CaO, x{sub 3} (2-6 g), amount of water, x{sub 4} (90-110 mL), and hydration temperature, x{sub 5} (150-250{sup o}C). The mathematical model developed was subjected to statistical tests and the model is adequate for predicting the SO{sub 2} desulfurization activity of the sorbent within the range of the sorbent preparation variables studied. Based on the model, the amount of RHA, amount of CaO, and hydration period used in the preparation step significantly influenced the desulfurization activity of the sorbent. The ratio of RHA and CaO used in the preparation mixture was also a significant factor that influenced the desulfurization activity of the sorbent. A RHA to CaO ratio of 2.5 leads to the formation of specific reactive species in the sorbent that are believed to be the key factor responsible for high desulfurization activity in the sorbent. Other physical properties of the sorbent such as pore size distribution and surface morphology were found to have insignificant influence on the desulfurization activity of the sorbent. 31 refs., 5 figs., 3 tabs.

  6. Biochemical evidence of key residues for the activation and autoprocessing of tomato type II metacaspase.

    PubMed

    Wen, Shuai; Ma, Qiu-Min; Zhang, Ya-Li; Yang, Ji-Ping; Zhao, Guang-Hua; Fu, Da-Qi; Luo, Yun-Bo; Qu, Gui-Qin

    2013-08-19

    To investigate the autolysis pattern and activation of metacaspase in higher plants, the biochemical characteristics of purified recombinant type II metacaspase (LeMCA1) from tomato were explored. Western blotting analysis indicated that four cleaved bands were formed; two N-terminal fragments and two C-terminal fragments. N-terminal sequencing confirmed that LeMCA1 cleaves at Lys223 and Arg332. Site mutants indicated that catalytic Cys139, cleaved Lys223, Arg332 and predicted calcium binding Asp116/Asp117 are the key residues that are responsible for its Ca²⁺ and pH dependent activation. The cleavage of the full-size fragment seemed crucial for the activation of LeMCA1 in vitro.

  7. Identifying key features of effective active learning: the effects of writing and peer discussion.

    PubMed

    Linton, Debra L; Pangle, Wiline M; Wyatt, Kevin H; Powell, Karli N; Sherwood, Rachel E

    2014-01-01

    We investigated some of the key features of effective active learning by comparing the outcomes of three different methods of implementing active-learning exercises in a majors introductory biology course. Students completed activities in one of three treatments: discussion, writing, and discussion + writing. Treatments were rotated weekly between three sections taught by three different instructors in a full factorial design. The data set was analyzed by generalized linear mixed-effect models with three independent variables: student aptitude, treatment, and instructor, and three dependent (assessment) variables: change in score on pre- and postactivity clicker questions, and coding scores on in-class writing and exam essays. All independent variables had significant effects on student performance for at least one of the dependent variables. Students with higher aptitude scored higher on all assessments. Student scores were higher on exam essay questions when the activity was implemented with a writing component compared with peer discussion only. There was a significant effect of instructor, with instructors showing different degrees of effectiveness with active-learning techniques. We suggest that individual writing should be implemented as part of active learning whenever possible and that instructors may need training and practice to become effective with active learning.

  8. Cold-water event of January 2010 results in catastrophic benthic mortality on patch reefs in the Florida Keys

    NASA Astrophysics Data System (ADS)

    Colella, M. A.; Ruzicka, R. R.; Kidney, J. A.; Morrison, J. M.; Brinkhuis, V. B.

    2012-06-01

    The Florida Keys are periodically exposed to extreme cold-water events that can have pronounced effects on coral reef community structure. In January 2010, the Florida Keys experienced one of the coldest 12-day periods on record, during which water temperatures decreased below the lethal limit for many tropical reef taxa for several consecutive days. This study provides a quantitative assessment of the scleractinian mortality and acute changes to benthic cover at four patch reefs in the middle and upper Keys that coincided with this cold-water event. Significant decreases in benthic cover of scleractinian corals, gorgonians, sponges, and macroalgae were observed between summer 2009 and February 2010. Gorgonian cover declined from 25.6 ± 4.6% (mean ± SE) to 13.3 ± 2.7%, scleractinian cover from 17.6 ± 1.4% to 10.7 ± 0.9%, macroalgal cover from 8.2 ± 5.2% to 0.7 ± 0.3%, and sponge cover from 3.8 ± 1.4% to 2.3 ± 1.2%. Scleractinian mortality varied across sites depending upon the duration of lethal temperatures and the community composition. Montastraea annularis complex cover was reduced from 4.4 ± 2.4% to 0.6 ± 0.2%, and 93% of all colonies surveyed suffered complete or partial mortality. Complete or partial mortality was also observed in >50% of all Porites astreoides and Montastraea cavernosa colonies and resulted in a significant reduction in cover. When compared with historical accounts of cold-water-induced mortality, our results suggest that the 2010 winter mortality was one of the most severe on record. The level of coral mortality on patch reefs is of particular concern because corals in these habitats had previously demonstrated resistance against stressors (e.g., disease and warm-water bleaching) that had negatively affected corals in other habitats in the Florida Keys during recent decades.

  9. Activity of key enzymes in glucose catabolism during the growth and metacyclogenesis of Leishmania infantum.

    PubMed

    Louassini, M; Foulquié, M R; Benítez, R; Adroher, F J

    1999-04-01

    This paper follows the development in the activity of the key enzymes of glycolysis and dehydrogenases of the pentose phosphate shunt throughout the in vitro growth and metacyclogenesis of two human strains of Leishmania infantum - one visceral (VL) and the other cutaneous (CL) - together with changes in the glucose, ammonium, and proton concentrations in the culture medium. In the first stage, ammonium was generated and no glucose was consumed. Later on, all the glucose was consumed and, finally, ammonium was generated again. The ammonium concentration increased 16- and 21-fold in cultures of VL and CL strains, respectively. The activities of the glycosomal enzymes hexokinase and phosphofructokinase differed in each strain, always being higher in CL than in VL and increasing throughout the culture period in CL while decreasing in VL. This probably indicates a different capability to adapt to the culture medium conditions. The activities of the pentose phosphate shunt enzymes examined indicate that 6-phosphogluconate dehydrogenase is possibly a rate-limiting enzyme for this pathway. Pyruvate kinase is a cytosolic control enzyme of glycolysis in trypanosomatids, and its activity decreased throughout the growth and differentiation of both strains of L. infantum, as occurs in other trypanosomatids. It was also observed that glucose catabolism was more active in the cutaneous strain than in the visceral one.

  10. The Hubble Space Telescope quasar absorption line key project. III - First observational results on Milky Way gas

    NASA Technical Reports Server (NTRS)

    Savage, Blair D.; Lu, Limin; Bahcall, John N.; Bergeron, Jacqueline; Boksenberg, Alec; Hartig, George F.; Jannuzi, Buell T.; Kirhakos, Sofia; Lockman, Felix J.; Sargent, W. L. W.

    1993-01-01

    Absorption lines found near zero redshift due to Milky Way disk and halo gas in the spectra of 15 quasars observed with the Faint Object Spectrograph (FOS) of the HST at a resolution of about 230 km/s are reported. Results show that Milky Way absorption lines comprise about 44 percent of all absorption lines seen in the first group of Key Project FOS spectra. Milky Way lines were observed for 3C 273 and H1821 + 643. Limits to the Mg-to-H abundance ratio obtained for very high velocity Mg II absorption detections imply gas-phase Mg abundances for the very high velocity gas ranging from more than 0.059 to more than 0.32 times the solar abundance. In all cases where high-velocity H I emission is seen, corresponding high-velocity metal-line absorption is observed.

  11. Casein kinase 1δ activity: a key element in the zebrafish circadian timing system.

    PubMed

    Smadja Storz, Sima; Tovin, Adi; Mracek, Philipp; Alon, Shahar; Foulkes, Nicholas S; Gothilf, Yoav

    2013-01-01

    Zebrafish have become a popular model for studies of the circadian timing mechanism. Taking advantage of its rapid development of a functional circadian clock and the availability of light-entrainable clock-containing cell lines, much knowledge has been gained about the circadian clock system in this species. However, the post-translational modifications of clock proteins, and in particular the phosphorylation of PER proteins by Casein kinase I delta and epsilon (CK1δ and CK1ε), have so far not been examined in the zebrafish. Using pharmacological inhibitors for CK1δ and CK1ε, a pan-CK1δ/ε inhibitor PF-670462, and a CK1ε -selective inhibitor PF-4800567, we show that CK1δ activity is crucial for the functioning of the circadian timing mechanism of zebrafish, while CK1ε plays a minor role. The CK1δ/ε inhibitor disrupted circadian rhythms of promoter activity in the circadian clock-containing zebrafish cell line, PAC-2, while the CK1ε inhibitor had no effect. Zebrafish larvae that were exposed to the CK1δ/ε inhibitor showed no rhythms of locomotor activity while the CK1ε inhibitor had only a minor effect on locomotor activity. Moreover, the addition of the CK1δ/ε inhibitor disrupted rhythms of aanat2 mRNA expression in the pineal gland. The pineal gland is considered to act as a central clock organ in fish, delivering a rhythmic hormonal signal, melatonin, which is regulated by AANAT2 enzymatic activity. Therefore, CK1δ plays a key role in the circadian timing system of the zebrafish. Furthermore, the effect of CK1δ inhibition on rhythmic locomotor activity may reflect its effect on the function of the central clock in the pineal gland as well as its regulation of peripheral clocks.

  12. 25 CFR 558.2 - Review of notice of results for a key employee or primary management official.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... management official. 558.2 Section 558.2 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR GAMING LICENSES AND BACKGROUND INVESTIGATIONS FOR KEY EMPLOYEES AND PRIMARY MANAGEMENT OFFICIALS GAMING LICENSES FOR KEY EMPLOYEES AND PRIMARY MANAGEMENT OFFICIALS § 558.2 Review of notice of...

  13. 25 CFR 558.2 - Review of notice of results for a key employee or primary management official.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... management official. 558.2 Section 558.2 Indians NATIONAL INDIAN GAMING COMMISSION, DEPARTMENT OF THE INTERIOR GAMING LICENSES AND BACKGROUND INVESTIGATIONS FOR KEY EMPLOYEES AND PRIMARY MANAGEMENT OFFICIALS GAMING LICENSES FOR KEY EMPLOYEES AND PRIMARY MANAGEMENT OFFICIALS § 558.2 Review of notice of...

  14. I 5683 you: dialing phone numbers on cell phones activates key-concordant concepts.

    PubMed

    Topolinski, Sascha

    2011-03-01

    When people perform actions, effects associated with the actions are activated mentally, even if those effects are not apparent. This study tested whether sequences of simulations of virtual action effects can be integrated into a meaning of their own. Cell phones were used to test this hypothesis because pressing a key on a phone is habitually associated with both digits (dialing numbers) and letters (typing text messages). In Experiment 1, dialing digit sequences induced the meaning of words that share the same key sequence (e.g., 5683, LOVE). This occurred even though the letters were not labeled on the keypad, and participants were not aware of the digit-letter correspondences. In Experiment 2, subjects preferred dialing numbers implying positive words (e.g., 37326, DREAM) over dialing numbers implying negative words (e.g., 75463, SLIME). In Experiment 3, subjects preferred companies with phone numbers implying a company-related word (e.g., LOVE for a dating agency, CORPSE for a mortician) compared with companies with phone numbers implying a company-unrelated word.

  15. Colorectal Cancer Screening Programme in Spain: Results of Key Performance Indicators After Five Rounds (2000–2012)

    PubMed Central

    Binefa, Gemma; Garcia, Montse; Milà, Núria; Fernández, Esteve; Rodríguez-Moranta, Francisco; Gonzalo, Núria; Benito, Llúcia; Clopés, Ana; Guardiola, Jordi; Moreno, Víctor

    2016-01-01

    Effective quality assurance is essential in any screening programme. This article provides a unique insight into key quality indicators of five rounds of the first population-based colorectal cancer screening programme implemented in Spain (2000–2012), providing the results according to the type of screening (prevalent or first screen and incident or subsequent screen) and test (guaiac or immunochemical). The total crude participation rate increased from 17.2% (11,011) in the first round to 35.9% (22,988) in the last one. Rescreening rate was very high (88.6% in the fifth round). Positivity rate was superior with the faecal immunochemical test (6.2%) than with the guaiac-based test (0.7%) (p < 0.0001) and detection rates were also better with the immunochemical test. The most significant rise in detection rate was observed for high risk adenoma in men (45.5 per 1,000 screened). Most cancers were diagnosed at an early stage (61.4%) and there was a statistically significant difference between those detected in first or subsequent screening (52.6% and 70.0% respectively; p = 0.024). The availability of these results substantially improves data comparisons and the exchange of experience between screening programmes. PMID:26787510

  16. Effects of gas periodic stimulation on key enzyme activity in gas double-dynamic solid state fermentation (GDD-SSF).

    PubMed

    Chen, Hongzhang; Shao, Meixue; Li, Hongqiang

    2014-03-05

    The heat and mass transfer have been proved to be the important factors in air pressure pulsation for cellulase production. However, as process of enzyme secretion, the cellulase formation has not been studied in the view of microorganism metabolism and metabolic key enzyme activity under air pressure pulsation condition. Two fermentation methods in ATPase activity, cellulase productivity, weight lose rate and membrane permeability were systematically compared. Results indicated that gas double-dynamic solid state fermentation had no obviously effect on cell membrane permeability. However, the relation between ATPase activity and weight loss rate was linearly dependent with r=0.9784. Meanwhile, the results also implied that gas periodic stimulation had apparently strengthened microbial metabolism through increasing ATPase activity during gas double-dynamic solid state fermentation, resulting in motivating the production of cellulase by Trichoderma reesei YG3. Therefore, the increase of ATPase activity would be another crucial factor to strengthen fermentation process for cellulase production under gas double-dynamic solid state fermentation.

  17. Carotenoid derivatives inhibit nuclear factor kappa B activity in bone and cancer cells by targeting key thiol groups.

    PubMed

    Linnewiel-Hermoni, Karin; Motro, Yair; Miller, Yifat; Levy, Joseph; Sharoni, Yoav

    2014-10-01

    Aberrant activation of the nuclear factor kappa B (NFkB) transcription system contributes to cancer progression, and has a harmful effect on bone health. Several major components of the NFkB pathway such as IkB Kinase (IKK) and the NFkB subunits contain cysteine residues that are critical for their activity. The interaction of electrophiles with these cysteine residues results in NFkB inhibition. Carotenoids, hydrophobic plant pigments, are devoid of electrophilic groups, and we have previously demonstrated that carotenoid derivatives, but not the native compounds activate the Nrf2 transcription system. The aim of the current study was to examine whether carotenoid derivatives inhibit NFkB, and, if so, to determine the molecular mechanism underpinning the inhibitory action. We report in the present study that a mixture of oxidized derivatives, prepared by ethanol extraction from partially oxidized lycopene preparation, inhibited NFkB reporter gene activity. In contrast, the intact carotenoid was inactive. A series of synthetic dialdehyde carotenoid derivatives inhibited reporter activity as well as several stages of the NFkB pathway in both cancer and bone cells. The activity of the carotenoid derivatives depended on the reactivity of the electrophilic groups in reactions such as Michael addition to sulfhydryl groups of proteins. Specifically, carotenoid derivatives directly interacted with two key proteins of the NFkB pathway: the IKKβ and the p65 subunit. Direct interaction with IKKβ was found in an in vitro kinase assay with a recombinant enzyme. The inhibition by carotenoid derivatives of p65 transcriptional activity was observed in a reporter gene assay performed in the presence of excess p65. This inhibition action resulted, at least in part, from direct interaction of the carotenoid derivative with p65 leading to reduced binding of the protein to DNA as evidenced by electrophoretic mobility shift assay (EMSA) experiments. Importantly, we found by using

  18. How to Tackle Key Challenges in the Promotion of Physical Activity among Older Adults (65+): The AEQUIPA Network Approach.

    PubMed

    Forberger, Sarah; Bammann, Karin; Bauer, Jürgen; Boll, Susanne; Bolte, Gabriele; Brand, Tilman; Hein, Andreas; Koppelin, Frauke; Lippke, Sonia; Meyer, Jochen; Pischke, Claudia R; Voelcker-Rehage, Claudia; Zeeb, Hajo

    2017-04-04

    The paper introduces the theoretical framework and methods/instruments used by the Physical Activity and Health Equity: Primary Prevention for Healthy Ageing (AEQUIPA) prevention research network as an interdisciplinary approach to tackle key challenges in the promotion of physical activity among older people (65+). Drawing on the social-ecological model, the AEQUIPA network developed an interdisciplinary methodological design including quantitative/qualitative studies and systematic reviews, while combining expertise from diverse fields: public health, psychology, urban planning, sports sciences, health technology and geriatrics. AEQUIPA tackles key challenges when promoting physical activity (PA) in older adults: tailoring of interventions, fostering community readiness and participation, strengthening intersectoral collaboration, using new technological devices and evaluating intervention generated inequalities. AEQUIPA aims to strengthen the evidence base for age-specific preventive PA interventions and to yield new insights into the explanatory power of individual and contextual factors. Currently, the empirical work is still underway. First experiences indicate that thenetwork has achieved a strong regional linkage with communities, local stakeholders and individuals. However, involving inactive persons and individuals from minority groups remained challenging. A review of existing PA intervention studies among the elderly revealed the potential to assess equity effects. The results will add to the theoretical and methodological discussion on evidence-based age-specific PA interventions and will contribute to the discussion about European and national health targets.

  19. PLASMINOGEN ACTIVATOR INHIBITOR-1 (PAI-1): A KEY FACTOR LINKING FIBRINOLYSIS AND AGE-RELATED SUBCLINICAL AND CLINICAL CONDITIONS

    PubMed Central

    Cesari, Matteo; Pahor, Marco; Incalzi, Raffaele Antonelli

    2010-01-01

    The close relationship existing between aging and thrombosis has growingly been studied in this last decade. The age-related development of a pro-thrombotic imbalance in the fibrinolysis homeostasis has been hypothesized at the basis of this increased cardiovascular and cerebrovascular risk. Fibrinolysis is the resulting of the interactions among multiple plasminogen activators and inhibitors constituing the enzymatic cascade, and ultimately leading to the degradation of fibrin. The plasminogen activator system plays a key role in a wide range of physiological and pathological processes. Plasminogen activator inhibitor-1 (PAI-1) is a member of the superfamily of serine-protease inhibitors (or serpins), and the principal inhibitor of both the tissue-type and the urinary-type plasminogen activator, the two plasminogen activators able to activate plasminogen. In this review, current evidence describing the central role played by PAI-1 in a number of age-related subclinical (i.e., inflammation, atherosclerosis, insulin resistance) and clinical (i.e., obesity, comorbidities, Werner syndrome) conditions is presented. Despite some controversial and unclear issues, PAI-1 represents an extremely promising marker which may become a biological parameter to be growingly considered in the prognostic evaluation, in the disease monitoring, and as treatment target of age-related conditions in the next future. PMID:20626406

  20. Unlocking Doors without Keys: Activation of Src by Truncated C-terminal Intracellular Receptor Tyrosine Kinases Lacking Tyrosine Kinase Activity

    PubMed Central

    Mezquita, Belén; Mezquita, Pau; Pau, Montserrat; Mezquita, Jovita; Mezquita, Cristóbal

    2014-01-01

    One of the best examples of the renaissance of Src as an open door to cancer has been the demonstration that just five min of Src activation is sufficient for transformation and also for induction and maintenance of cancer stem cells [1]. Many tyrosine kinase receptors, through the binding of their ligands, become the keys that unlock the structure of Src and activate its oncogenic transduction pathways. Furthermore, intracellular isoforms of these receptors, devoid of any tyrosine kinase activity, still retain the ability to unlock Src. This has been shown with a truncated isoform of KIT (tr-KIT) and a truncated isoform of VEGFR-1 (i21-VEGFR-1), which are intracellular and require no ligand binding, but are nonetheless able to activate Src and induce cell migration and invasion of cancer cells. Expression of the i21-VEGFR-1 is upregulated by the Notch signaling pathway and repressed by miR-200c and retinoic acid in breast cancer cells. Both Notch inhibitors and retinoic acid have been proposed as potential therapies for invasive breast cancer. PMID:24709904

  1. Quantification of key long-term risks at CO₂ sequestration sites: Latest results from US DOE's National Risk Assessment Partnership (NRAP) Project

    DOE PAGES

    Pawar, Rajesh; Bromhal, Grant; Carroll, Susan; ...

    2014-12-31

    Risk assessment for geologic CO₂ storage including quantification of risks is an area of active investigation. The National Risk Assessment Partnership (NRAP) is a US-Department of Energy (US-DOE) effort focused on developing a defensible, science-based methodology and platform for quantifying risk profiles at geologic CO₂ sequestration sites. NRAP has been developing a methodology that centers round development of an integrated assessment model (IAM) using system modeling approach to quantify risks and risk profiles. The IAM has been used to calculate risk profiles with a few key potential impacts due to potential CO₂ and brine leakage. The simulation results are alsomore » used to determine long-term storage security relationships and compare the long-term storage effectiveness to IPCC storage permanence goal. Additionally, we also demonstrate application of IAM for uncertainty quantification in order to determine parameters to which the uncertainty in model results is most sensitive.« less

  2. Quantification of key long-term risks at CO₂ sequestration sites: Latest results from US DOE's National Risk Assessment Partnership (NRAP) Project

    SciTech Connect

    Pawar, Rajesh; Bromhal, Grant; Carroll, Susan; Chu, Shaoping; Dilmore, Robert; Gastelum, Jason; Oldenburg, Curt; Stauffer, Philip; Zhang, Yingqi; Guthrie, George

    2014-12-31

    Risk assessment for geologic CO₂ storage including quantification of risks is an area of active investigation. The National Risk Assessment Partnership (NRAP) is a US-Department of Energy (US-DOE) effort focused on developing a defensible, science-based methodology and platform for quantifying risk profiles at geologic CO₂ sequestration sites. NRAP has been developing a methodology that centers round development of an integrated assessment model (IAM) using system modeling approach to quantify risks and risk profiles. The IAM has been used to calculate risk profiles with a few key potential impacts due to potential CO₂ and brine leakage. The simulation results are also used to determine long-term storage security relationships and compare the long-term storage effectiveness to IPCC storage permanence goal. Additionally, we also demonstrate application of IAM for uncertainty quantification in order to determine parameters to which the uncertainty in model results is most sensitive.

  3. New seismic reflection results in the central Eromanga Basin, Queensland, Australia: The key to understanding its tectonic evolution

    NASA Astrophysics Data System (ADS)

    Wake-Dyster, K. D.; Moss, F. J.; Sexton, M. J.

    1983-12-01

    Regional seismic traverses were recorded from 1980 to 1982 by the Bureau of Mineral Resources, Geology and Geophysics as part of a major multidisciplinary program aimed at studying the geological evolution of the central Eromanga Basin area and its petroleum potential. Six-fold CDP reflection data were obtained to 20 s reflection time on 1400 km of traverses, up to 400 km long, crossing the main structural features of the area. Additional seismic reflection information to complement the study was obtained from 2300 km of older, mainly single coverage analogue data, which was transcribed to digital format and reprocessed. The central Eromanga Basin area has a complex history and contains four Phanerozoic potentially hydrocarbon-bearing basins each separated by unconformities, i.e. the Devonian Adavale Basin, the Late Carboniferous to Triassic Cooper and Galilee basins, and the Jurassic-Cretaceous Eromanga Basin. The seismic results are being interpreted, with the aid of synthetic seismograms from key wells, to provide information on the extent, nature and relationship of these basins. The quality of the reflection data from the Devonian sequence is generally very good and these data are proving to be most useful in the study. Thick Devonian sediments were deposited over a wide area well beyond the present confines of the Adavale Basin and its associated troughs. Intensive folding and faulting accompanied by major basement uplift, including the Canaway Ridge in the centre of the area, took place during the mid-Carboniferous Kanimblan Orogeny. This was followed by a period of erosion which truncated the Devonian sequence and resulted in separation of the Adavale Basin from the other Devonian Troughs in the area. The preliminary seismic results give some indication also of the extent and nature of the Cooper and Galilee basins sediments. These are generally thin in the central area and thicken to the west and east respectively where coal measures produce good

  4. Constructing a Cross-Domain Resource Inventory: Key Components and Results of the EarthCube CINERGI Project.

    NASA Astrophysics Data System (ADS)

    Zaslavsky, I.; Richard, S. M.; Malik, T.; Hsu, L.; Gupta, A.; Grethe, J. S.; Valentine, D. W., Jr.; Lehnert, K. A.; Bermudez, L. E.; Ozyurt, I. B.; Whitenack, T.; Schachne, A.; Giliarini, A.

    2015-12-01

    While many geoscience-related repositories and data discovery portals exist, finding information about available resources remains a pervasive problem, especially when searching across multiple domains and catalogs. Inconsistent and incomplete metadata descriptions, disparate access protocols and semantic differences across domains, and troves of unstructured or poorly structured information which is hard to discover and use are major hindrances toward discovery, while metadata compilation and curation remain manual and time-consuming. We report on methodology, main results and lessons learned from an ongoing effort to develop a geoscience-wide catalog of information resources, with consistent metadata descriptions, traceable provenance, and automated metadata enhancement. Developing such a catalog is the central goal of CINERGI (Community Inventory of EarthCube Resources for Geoscience Interoperability), an EarthCube building block project (earthcube.org/group/cinergi). The key novel technical contributions of the projects include: a) development of a metadata enhancement pipeline and a set of document enhancers to automatically improve various aspects of metadata descriptions, including keyword assignment and definition of spatial extents; b) Community Resource Viewers: online applications for crowdsourcing community resource registry development, curation and search, and channeling metadata to the unified CINERGI inventory, c) metadata provenance, validation and annotation services, d) user interfaces for advanced resource discovery; and e) geoscience-wide ontology and machine learning to support automated semantic tagging and faceted search across domains. We demonstrate these CINERGI components in three types of user scenarios: (1) improving existing metadata descriptions maintained by government and academic data facilities, (2) supporting work of several EarthCube Research Coordination Network projects in assembling information resources for their domains

  5. Geology is the Key to Explain Igneous Activity in the Mediterranean Area

    NASA Astrophysics Data System (ADS)

    Lustrino, M.

    2014-12-01

    Igneous activity in tectonically complex areas can be interpreted in many different ways, producing completely different petrogenetic models. Processes such as oceanic and continental subduction, lithospheric delamination, changes in subduction polarity, slab break-off and mantle plumes have all been advocated as causes for changes in plate boundaries and magma production, including rate and temporal distribution, in the circum-Mediterranean area. This region thus provides a natural laboratory to investigate a range of geodynamic and magmatic processes. Although many petrologic and tectonic models have been proposed, a number of highly controversial questions still remain. No consensus has yet been reached about the capacity of plate-tectonic processes to explain the origin and style of the magmatism. Similarly, there is still not consensus on the ability of geochemical and petrological arguments to reveal the geodynamic evolution of the area. The wide range of chemical and mineralogical magma compositions produced within and around the Mediterranean, from carbonatites to strongly silica-undersaturated silico-carbonatites and melilitites to strongly silica-oversaturated rhyolites, complicate models and usually require a large number of unconstrained assumptions. Can the calcalkaline-sodic alkaline transition be related to any common petrogenetic point? Is igneous activity plate-tectonic- (top-down) or deep-mantle-controlled (bottom-up)? Do the rare carbonatites and carbonate-rich igneous rocks derive from the deep mantle or a normal, CO2-bearing upper mantle? Do ultrapotassic compositions require continental subduction? Understanding chemically complex magmas emplaced in tectonically complex areas require open minds, and avoiding dogma and assumptions. Studying the geology and shallow dynamics, not speculating about the deep lower mantle, is the key to understanding the igneous activity.

  6. Occupancy by key transcription factors is a more accurate predictor of enhancer activity than histone modifications or chromatin accessibility

    SciTech Connect

    Dogan, Nergiz; Wu, Weisheng; Morrissey, Christapher S.; Chen, Kuan-Bei; Stonestrom, Aaron; Long, Maria; Keller, Cheryl A.; Cheng, Yong; Jain, Deepti; Visel, Axel; Pennacchio, Len A.; Weiss, Mitchell J.; Blobel, Gerd A.; Hardison, Ross C.

    2015-04-23

    Regulated gene expression controls organismal development, and variation in regulatory patterns has been implicated in complex traits. Thus accurate prediction of enhancers is important for further understanding of these processes. Genome-wide measurement of epigenetic features, such as histone modifications and occupancy by transcription factors, is improving enhancer predictions, but the contribution of these features to prediction accuracy is not known. Given the importance of the hematopoietic transcription factor TAL1 for erythroid gene activation, we predicted candidate enhancers based on genomic occupancy by TAL1 and measured their activity. Contributions of multiple features to enhancer prediction were evaluated based on the results of these and other studies. Results: TAL1-bound DNA segments were active enhancers at a high rate both in transient transfections of cultured cells (39 of 79, or 56%) and transgenic mice (43 of 66, or 65%). The level of binding signal for TAL1 or GATA1 did not help distinguish TAL1-bound DNA segments as active versus inactive enhancers, nor did the density of regulation-related histone modifications. A meta-analysis of results from this and other studies (273 tested predicted enhancers) showed that the presence of TAL1, GATA1, EP300, SMAD1, H3K4 methylation, H3K27ac, and CAGE tags at DNase hypersensitive sites gave the most accurate predictors of enhancer activity, with a success rate over 80% and a median threefold increase in activity. Chromatin accessibility assays and the histone modifications H3K4me1 and H3K27ac were sensitive for finding enhancers, but they have high false positive rates unless transcription factor occupancy is also included. Conclusions: Occupancy by key transcription factors such as TAL1, GATA1, SMAD1, and EP300, along with evidence of transcription, improves the accuracy of enhancer predictions based on epigenetic features.

  7. Photocatalytic Properties of TiO2: Evidence of the Key Role of Surface Active Sites in Water Oxidation.

    PubMed

    Bak, Tadeusz; Li, Wenxian; Nowotny, Janusz; Atanacio, Armand J; Davis, Joel

    2015-09-10

    Photocatalytic activity of oxide semiconductors is commonly considered in terms of the effect of the band gap on the light-induced performance. The present work considers a combined effect of several key performance-related properties (KPPs) on photocatalytic activity of TiO2 (rutile), including the chemical potential of electrons (Fermi level), the concentration of surface active sites, and charge transport, in addition to the band gap. The KPPs have been modified using defect engineering. This approach led to imposition of different defect disorders and the associated KPPs, which are defect-related. This work shows, for the first time, a competitive influence of different KPPs on photocatalytic activity that was tested using oxidation of methylene blue (MB). It is shown that the increase of oxygen activity in the TiO2 lattice from 10(-12) Pa to 10(5) Pa results in (i) increase in the band gap from 2.42 to 2.91 eV (direct transitions) or 2.88 to 3 eV (indirect transitions), (ii) increase in the population of surface active sites, (iii) decrease of the Fermi level, and (iv) decrease of the charge transport. It is shown that the observed changes in the photocatalytic activity are determined by two dominant KPPs: the concentration of active surface sites and the Fermi level, while the band gap and charge transport have a minor effect on the photocatalytic performance. The effect of the defect-related properties on photoreactivity of TiO2 with water is considered in terms of a theoretical model offering molecular-level insight into the process.

  8. Plutonium recycle test reactor characterization activities and results

    SciTech Connect

    Cornwell, B.C.

    1997-05-01

    Report contains results of PRTR core and associated structures characterization performed in January and February of 1997. Radiation survey data are presented, along with recommendations for stabilization activities before transitioning to a decontamination and decommissioning function. Recommendations are also made about handling the waste generated by the stabilization activities, and actions suggested by the Decontamination and Decommissioning organization.

  9. Toll-like receptors: key activators of leucocytes and regulator of haematopoiesis.

    PubMed

    McGettrick, Anne F; O'Neill, Luke A J

    2007-10-01

    Toll-like receptors (TLRs) play a critical role in the induction of the immune response to invading pathogens. The detection of pathogens by TLRs initiates a signalling cascade that results in the activation of transcription factors such as nuclear factor (NF)-kappaB and interferon regulatory factors leading to the production of pro-inflammatory cytokines and type 1 interferons. Five cytoplasmic adaptors, MyD88, Mal, Trif, TRAM and SARM, are utilized by the TLRs to activate these signalling pathways. Through the years the main focus of research has been on the activation and function of TLRs in monocytic cells. This review discusses several additional roles of TLRs. TLR activation plays a role in influencing the differentiation of haematopoietic stem cells. Their activation also prevents apoptosis in neutrophils following pathogen invasion. B cells and T cells proliferation and differentiation is influenced by TLR activation and the possible therapeutic benefits of using TLR ligands for the treatment of chronic lymphocytic leukaemia will also be discussed.

  10. Key Factors Influencing Rates of Heterotrophic Sulfate Reduction in Active Seafloor Hydrothermal Massive Sulfide Deposits

    PubMed Central

    Frank, Kiana L.; Rogers, Karyn L.; Rogers, Daniel R.; Johnston, David T.; Girguis, Peter R.

    2015-01-01

    Hydrothermal vents are thermally and geochemically dynamic habitats, and the organisms therein are subject to steep gradients in temperature and chemistry. To date, the influence of these environmental dynamics on microbial sulfate reduction has not been well constrained. Here, via multivariate experiments, we evaluate the effects of key environmental variables (temperature, pH, H2S, SO42−, DOC) on sulfate reduction rates and metabolic energy yields in material recovered from a hydrothermal flange from the Grotto edifice in the Main Endeavor Field, Juan de Fuca Ridge. Sulfate reduction was measured in batch reactions across a range of physico-chemical conditions. Temperature and pH were the strongest stimuli, and maximum sulfate reduction rates were observed at 50°C and pH 6, suggesting that the in situ community of sulfate-reducing organisms in Grotto flanges may be most active in a slightly acidic and moderate thermal/chemical regime. At pH 4, sulfate reduction rates increased with sulfide concentrations most likely due to the mitigation of metal toxicity. While substrate concentrations also influenced sulfate reduction rates, energy-rich conditions muted the effect of metabolic energetics on sulfate reduction rates. We posit that variability in sulfate reduction rates reflect the response of the active microbial consortia to environmental constraints on in situ microbial physiology, toxicity, and the type and extent of energy limitation. These experiments help to constrain models of the spatial contribution of heterotrophic sulfate reduction within the complex gradients inherent to seafloor hydrothermal deposits. PMID:26733984

  11. T-2 toxin inhibits gene expression and activity of key steroidogenesis enzymes in mouse Leydig cells.

    PubMed

    Yang, Jian Ying; Zhang, Yong Fa; Meng, Xiang Ping; Li, Yuan Xiao; Ma, Kai Wang; Bai, Xue Fei

    2015-08-01

    T-2 toxin is one of the mycotoxins, a group of type A trichothecenes produced by several fungal genera including Fusarium species, which may lead to the decrease of the testosterone secretion in the primary Leydig cells derived from the mouse testis. The previous study demonstrated the effects of T-2 toxin through direct decrease of the testosterone biosynthesis in the primary Leydig cells derived from the mouse testis. In this study, we further examined the direct biological effects of T-2 toxin on steroidogenesis production, primarily in Leydig cells of mice. Mature mouse Leydig cells were purified by Percoll gradient centrifugation and the cell purity was determined by 3β-hydroxysteroid dehydrogenase (3β-HSD) staining. To examine T-2 toxin-induced testosterone secretion decrease, we measured the transcription levels of 3 key steroidogenic enzymes and 5 enzyme activities including 3β-HSD-1, P450scc, StAR, CYP17A1, and 17β-HSD in T-2 toxin/human chorionicgonadotropin (hCG) co-treated cells. Our previous study showed that T-2 toxin (10(-7) M, 10(-8) M and 10(-9) M) significantly suppressed hCG (10 ng/ml)-induced testosterone secretion. The studies demonstrated that the suppressive effect is correlated with the decreases in the levels of transcription of 3β-HSD-1, P450scc, and StAR (P<0.05) and also in enzyme activities of 3β-HSD-1, P450scc, StAR, CYP17A1, and 17β-HSD (P<0.05).

  12. Antenna Heights for the Optimum Utilization of the Oceanic Evaporation Duct. Part 1. Results from the Pacific Measurements. Part 2. Results from the Key West Measurements. Volume 1

    DTIC Science & Technology

    1988-01-01

    evaporation ducting measurements wore conducted over a period of 1 year in the Southern California off- shore area and for 2 weeks between Key Wast and the...WORD In the early 1970s, a series of extensive evaporation ducting measurements was conducted in different ocean areas . The purpose of the measurements...period of one year in the Southern California off-shore area . The purpose of the measurements was to determine antenna heights for optimum

  13. Deletion of the carboxyl-terminal region of 1-aminocyclopropane-1-carboxylic acid synthase, a key protein in the biosynthesis of ethylene, results in catalytically hyperactive, monomeric enzyme.

    PubMed

    Li, N; Mattoo, A K

    1994-03-04

    1-Aminocyclopropane-1-carboxylic acid (ACC) synthase is a key enzyme regulating biosynthesis of the plant hormone ethylene. The expression of an enzymatically active, wound-inducible tomato (Lycopersicon esculentum L. cv Pik-Red) ACC synthase (485 amino acids long) in a heterologous Escherichia coli system allowed us to study the importance of hypervariable COOH terminus in enzymatic activity and protein conformation. We constructed several deletion mutants of the gene, expressed these in E. coli, purified the protein products to apparent homogeneity, and analyzed both conformation and enzyme kinetic parameters of the wild-type and truncated ACC syntheses. Deletion of the COOH terminus through Arg429 results in complete inactivation of the enzyme. Deletion of 46-52 amino acids from the COOH terminus results in an enzyme that has nine times higher affinity for the substrate S-adenosylmethionine than the wild-type enzyme. The highly efficient, truncated ACC synthase was found to be a monomer of 52 +/- 1.8 kDa as determined by gel filtration, whereas the wild-type ACC synthase, analyzed under similar conditions, is a dimer. These results demonstrate that the non-conserved COOH terminus of ACC synthase affects its enzymatic function as well as dimerization.

  14. Occupancy by key transcription factors is a more accurate predictor of enhancer activity than histone modifications or chromatin accessibility

    DOE PAGES

    Dogan, Nergiz; Wu, Weisheng; Morrissey, Christapher S.; ...

    2015-04-23

    Regulated gene expression controls organismal development, and variation in regulatory patterns has been implicated in complex traits. Thus accurate prediction of enhancers is important for further understanding of these processes. Genome-wide measurement of epigenetic features, such as histone modifications and occupancy by transcription factors, is improving enhancer predictions, but the contribution of these features to prediction accuracy is not known. Given the importance of the hematopoietic transcription factor TAL1 for erythroid gene activation, we predicted candidate enhancers based on genomic occupancy by TAL1 and measured their activity. Contributions of multiple features to enhancer prediction were evaluated based on the resultsmore » of these and other studies. Results: TAL1-bound DNA segments were active enhancers at a high rate both in transient transfections of cultured cells (39 of 79, or 56%) and transgenic mice (43 of 66, or 65%). The level of binding signal for TAL1 or GATA1 did not help distinguish TAL1-bound DNA segments as active versus inactive enhancers, nor did the density of regulation-related histone modifications. A meta-analysis of results from this and other studies (273 tested predicted enhancers) showed that the presence of TAL1, GATA1, EP300, SMAD1, H3K4 methylation, H3K27ac, and CAGE tags at DNase hypersensitive sites gave the most accurate predictors of enhancer activity, with a success rate over 80% and a median threefold increase in activity. Chromatin accessibility assays and the histone modifications H3K4me1 and H3K27ac were sensitive for finding enhancers, but they have high false positive rates unless transcription factor occupancy is also included. Conclusions: Occupancy by key transcription factors such as TAL1, GATA1, SMAD1, and EP300, along with evidence of transcription, improves the accuracy of enhancer predictions based on epigenetic features.« less

  15. Effect of urethane, dimethylnitrosamine, paraquat, and butylated hydroxytoluene on the activities of glycolytic key enzymes in mouse lung

    SciTech Connect

    Arany, I.; Rady, P.; Bojan, I.; Kertai, P.

    1981-12-01

    Effects of carcinogens and noncarcinogenic pulmonary toxicants on the activities of glycolytic key enzymes in the mouse lung were investigated. The carcinogens urethane (URTH) and dimethylnitrosamine (DMN) permanently enhanced, and the noncarcinogenic pulmonary toxicants paraquat (PAR) and butylated hydroxytoluene (BHT) temporarily, enhanced the activities of hexokinase (HK), phosphofructokinase (PFK), and pyruvate kinase (PK) in the lungs of mice.

  16. The importance of delineating networks by activity type in bottlenose dolphins (Tursiops truncatus) in Cedar Key, Florida

    PubMed Central

    Gazda, Stefanie; Iyer, Swami; Killingback, Timothy; Connor, Richard; Brault, Solange

    2015-01-01

    Network analysis has proved to be a valuable tool for studying the behavioural patterns of complex social animals. Often such studies either do not distinguish between different behavioural states of the organisms or simply focus attention on a single behavioural state to the exclusion of all others. In either of these approaches it is impossible to ascertain how the behavioural patterns of individuals depend on the type of activity they are engaged in. Here we report on a network-based analysis of the behavioural associations in a population of bottlenose dolphins (Tursiops truncatus) in Cedar Key, Florida. We consider three distinct behavioural states—socializing, travelling and foraging—and analyse the association networks corresponding to each activity. Moreover, in constructing the different activity networks we do not simply record a spatial association between two individuals as being either present or absent, but rather quantify the degree of any association, thus allowing us to construct weighted networks describing each activity. The results of these weighted activity networks indicate that networks can reveal detailed patterns of bottlenose dolphins at the population level; dolphins socialize in large groups with preferential associations; travel in small groups with preferential associates; and spread out to forage in very small, weakly connected groups. There is some overlap in the socialize and travel networks but little overlap between the forage and other networks. This indicates that the social bonds maintained in other activities are less important as they forage on dispersed, solitary prey. The overall network, not sorted by activity, does not accurately represent any of these patterns. PMID:26064611

  17. Catalytic efficiency of HAP phytases is determined by a key residue in close proximity to the active site.

    PubMed

    Fu, Dawei; Li, Zhongyuan; Huang, Huoqing; Yuan, Tiezheng; Shi, Pengjun; Luo, Huiying; Meng, Kun; Yang, Peilong; Yao, Bin

    2011-05-01

    The maximum activity of Yersinia enterocolitica phytase (YeAPPA) occurs at pH 5.0 and 45 °C, and notably, its specific activity (3.28 ± 0.24 U mg(-1)) is 800-fold less than that of its Yersinia kristeensenii homolog (YkAPPA; 88% amino acid sequence identity). Sequence alignment and molecular modeling show that the arginine at position 79 (Arg79) in YeAPPA corresponding to Gly in YkAPPA as well as other histidine acid phosphatase (HAP) phytases is the only non-conserved residue near the catalytic site. To characterize the effects of the corresponding residue on the specific activities of HAP phytases, Escherichia coli EcAPPA, a well-characterized phytase with a known crystal structure, was selected for mutagenesis-its Gly73 was replaced with Arg, Asp, Glu, Ser, Thr, Leu, or Tyr. The results show that the specific activities of all of the corresponding EcAPPA mutants (17-2,400 U mg(-1)) were less than that of the wild-type phytase (3,524 U mg(-1)), and the activity levels were approximately proportional to the molecular volumes of the substituted residues' side chains. Site-directed replacement of Arg79 in YeAPPA (corresponding to Gly73 of EcAPPA) with Ser, Leu, and Gly largely increased the specific activity, which further verified the key role of the residue at position 79 for determining phytase activity. Thus, a new determinant that influences the catalytic efficiency of HAP phytases has been identified.

  18. The time of day differently influences fatigue and locomotor activity: is body temperature a key factor?

    PubMed

    Machado, Frederico Sander Mansur; Rodovalho, Gisele Vieira; Coimbra, Cândido Celso

    2015-03-01

    The aim of this study was to verify the possible interactions between exercise capacity and spontaneous locomotor activity (SLA) during the oscillation of core body temperature (Tb) that occurs during the light/dark cycle. Wistar rats (n=11) were kept at an animal facility under a light/dark cycle of 14/10h at an ambient temperature of 23°C and water and food ad libitum. Initially, in order to characterize the daily oscillation in SLA and Tb of the rats, these parameters were continuously recorded for 24h using an implantable telemetric sensor (G2 E-Mitter). The animals were randomly assigned to two progressive exercise test protocols until fatigue during the beginning of light and dark-phases. Fatigue was defined as the moment rats could not keep pace with the treadmill. We assessed the time to fatigue, workload and Tb changes induced by exercise. Each test was separated by 3days. Our results showed that exercise capacity and heat storage were higher during the light-phase (p<0.05). In contrast, we observed that both SLA and Tb were higher during the dark-phase (p<0.01). Notably, the correlation analysis between the amount of SLA and the running capacity observed at each phase of the daily cycle revealed that, regardless of the time of the day, both types of locomotor physical activity have an important inherent component (r=0.864 and r=0.784, respectively, p<0.01) without a direct relationship between them. This finding provides further support for the existence of specific control mechanisms for each type of physical activity. In conclusion, our data indicate that the relationship between the body temperature and different types of physical activity might be affected by the light/dark cycle. These results mean that, although exercise performance and spontaneous locomotor activity are not directly associated, both are strongly influenced by daily cycles of light and dark.

  19. Spaceflight and simulated microgravity cause a significant reduction of key gene expression in early T-cell activation.

    PubMed

    Martinez, Emily M; Yoshida, Miya C; Candelario, Tara Lynne T; Hughes-Fulford, Millie

    2015-03-15

    Healthy immune function depends on precise regulation of lymphocyte activation. During the National Aeronautics and Space Administration (NASA) Apollo and Shuttle eras, multiple spaceflight studies showed depressed lymphocyte activity under microgravity (μg) conditions. Scientists on the ground use two models of simulated μg (sμg): 1) the rotating wall vessel (RWV) and 2) the random positioning machine (RPM), to study the effects of altered gravity on cell function before advancing research to the true μg when spaceflight opportunities become available on the International Space Station (ISS). The objective of this study is to compare the effects of true μg and sμg on the expression of key early T-cell activation genes in mouse splenocytes from spaceflight and ground animals. For the first time, we compared all three conditions of microgravity spaceflight, RPM, and RWV during immune gene activation of Il2, Il2rα, Ifnγ, and Tagap; moreover, we confirm two new early T-cell activation genes, Iigp1 and Slamf1. Gene expression for all samples was analyzed using quantitative real-time PCR (qRT-PCR). Our results demonstrate significantly increased gene expression in activated ground samples with suppression of mouse immune function in spaceflight, RPM, and RWV samples. These findings indicate that sμg models provide an excellent test bed for scientists to develop baseline studies and augment true μg in spaceflight experiments. Ultimately, sμg and spaceflight studies in lymphocytes may provide insight into novel regulatory pathways, benefiting both future astronauts and those here on earth suffering from immune disorders.

  20. Spaceflight and simulated microgravity cause a significant reduction of key gene expression in early T-cell activation

    PubMed Central

    Martinez, Emily M.; Yoshida, Miya C.; Candelario, Tara Lynne T.

    2015-01-01

    Healthy immune function depends on precise regulation of lymphocyte activation. During the National Aeronautics and Space Administration (NASA) Apollo and Shuttle eras, multiple spaceflight studies showed depressed lymphocyte activity under microgravity (μg) conditions. Scientists on the ground use two models of simulated μg (sμg): 1) the rotating wall vessel (RWV) and 2) the random positioning machine (RPM), to study the effects of altered gravity on cell function before advancing research to the true μg when spaceflight opportunities become available on the International Space Station (ISS). The objective of this study is to compare the effects of true μg and sμg on the expression of key early T-cell activation genes in mouse splenocytes from spaceflight and ground animals. For the first time, we compared all three conditions of microgravity spaceflight, RPM, and RWV during immune gene activation of Il2, Il2rα, Ifnγ, and Tagap; moreover, we confirm two new early T-cell activation genes, Iigp1 and Slamf1. Gene expression for all samples was analyzed using quantitative real-time PCR (qRT-PCR). Our results demonstrate significantly increased gene expression in activated ground samples with suppression of mouse immune function in spaceflight, RPM, and RWV samples. These findings indicate that sμg models provide an excellent test bed for scientists to develop baseline studies and augment true μg in spaceflight experiments. Ultimately, sμg and spaceflight studies in lymphocytes may provide insight into novel regulatory pathways, benefiting both future astronauts and those here on earth suffering from immune disorders. PMID:25568077

  1. KEY COMPARISON: Activity measurements of the radionuclide 153Sm for the ANSTO, Australia in the ongoing comparison BIPM.RI(II)-K1.Sm-153

    NASA Astrophysics Data System (ADS)

    Ratel, G.; Michotte, C.; Reinhard, M.; Alexiev, D.; Mo, L.

    2005-01-01

    In 2004, the Australian Nuclear Science and Technology Organisation (ANSTO) submitted two samples of known activity of 153Sm to the International Reference System (SIR). The value of the activity submitted was about 920 MBq. This key comparison result has been added to the matrix of degrees of equivalence in the key comparison database that now contains five results, identifier BIPM.RI(II)-K1.Sm-153. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by Section II of the Consultative Committee for Ionizing Radiation (CCRI(II)), according to the provisions of the Mutual Recognition Arrangement (MRA).

  2. Disrupting a key hydrophobic pair in the oligomerization interface of the actinoporins impairs their pore-forming activity.

    PubMed

    Mesa-Galloso, Haydeé; Delgado-Magnero, Karelia H; Cabezas, Sheila; López-Castilla, Aracelys; Hernández-González, Jorge E; Pedrera, Lohans; Alvarez, Carlos; Peter Tieleman, D; García-Sáez, Ana J; Lanio, Maria E; Ros, Uris; Valiente, Pedro A

    2017-03-01

    Crystallographic data of the dimeric and octameric forms of fragaceatoxin C (FraC) suggested the key role of a small hydrophobic protein-protein interaction surface for actinoporins oligomerization and pore formation in membranes. However, site-directed mutagenesis studies supporting this hypothesis for others actinoporins are still lacking. Here, we demonstrate that disrupting the key hydrophobic interaction between V60 and F163 (FraC numbering scheme) in the oligomerization interface of FraC, equinatoxin II (EqtII), and sticholysin II (StII) impairs the pore formation activity of these proteins. Our results allow for the extension of the importance of FraC protein-protein interactions in the stabilization of the oligomeric intermediates of StII and EqtII pointing out that all of these proteins follow a similar pathway of membrane disruption. These findings support the hybrid pore proposal as the universal model of actinoporins pore formation. Moreover, we reinforce the relevance of dimer formation, which appears to be a functional intermediate in the assembly pathway of some different pore-forming proteins.

  3. Identifying key areas for active interprofessional learning partnerships: A facilitated dialogue.

    PubMed

    Steven, Kathryn; Angus, Allyson; Breckenridge, Jenna; Davey, Peter; Tully, Vicki; Muir, Fiona

    2016-11-01

    Student and service user involvement is recognised as an important factor in creating interprofessional education (IPE) opportunities. We used a team-based learning approach to bring together undergraduate health professional students, early career professionals (ECPs), public partners, volunteers, and carers to explore learning partnerships. Influenced by evaluative inquiry, this qualitative study used a free text response to allow participants to give their own opinion. A total of 153 participants (50 public partners and 103 students and professionals representing 11 healthcare professions) took part. Participants were divided into mixed groups of six (n = 25) and asked to identify areas where students, professionals, and public could work together to improve health professional education. Each group documented their discussions by summarising agreed areas and next steps. Responses were collected and transcribed for inductive content analysis. Seven key themes (areas for joint working) were identified: communication, public as partners, standards of conduct, IPE, quality improvement, education, and learning environments. The team-based learning format enabled undergraduate and postgraduate health professionals to achieve consensus with public partners on areas for IPE and collaboration. Some of our results may be context-specific but the approach is generalisable to other areas.

  4. Silver residues as a possible key to a remarkable oxidative catalytic activity of nanoporous gold.

    PubMed

    Moskaleva, Lyudmila V; Röhe, Sarah; Wittstock, Arne; Zielasek, Volkmar; Klüner, Thorsten; Neyman, Konstantin M; Bäumer, Marcus

    2011-03-14

    Recently, several forms of unsupported gold were shown to display a remarkable activity to catalyze oxidation reactions. Experimental evidence points to the crucial role of residual silver present in very small concentrations in these novel catalysts. We focus on the catalytic properties of nanoporous gold (np-Au) foams probed via CO and oxygen adsorption/co-adsorption. Experimental results are analyzed using theoretical models represented by the flat Au(111) and the kinked Au(321) slabs with Ag impurities. We show that Ag atoms incorporated into gold surfaces can facilitate the adsorption and dissociation of molecular oxygen on them. CO adsorbed on top of 6-fold coordinated Au atoms can in turn be stabilized by co-adsorbed atomic oxygen by up to 0.2 eV with respect to the clean unsubstituted gold surface. Our experiments suggest a linking of that most strongly bound CO adsorption state to the catalytic activity of np-Au. Thus, our results shed light on the role of silver admixtures in the striking catalytic activity of unsupported gold nanostructures.

  5. Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains

    PubMed Central

    Ulianov, Sergey V.; Khrameeva, Ekaterina E.; Gavrilov, Alexey A.; Flyamer, Ilya M.; Kos, Pavel; Mikhaleva, Elena A.; Penin, Aleksey A.; Logacheva, Maria D.; Imakaev, Maxim V.; Chertovich, Alexander; Gelfand, Mikhail S.; Shevelyov, Yuri Y.; Razin, Sergey V.

    2016-01-01

    Recent advances enabled by the Hi-C technique have unraveled many principles of chromosomal folding that were subsequently linked to disease and gene regulation. In particular, Hi-C revealed that chromosomes of animals are organized into topologically associating domains (TADs), evolutionary conserved compact chromatin domains that influence gene expression. Mechanisms that underlie partitioning of the genome into TADs remain poorly understood. To explore principles of TAD folding in Drosophila melanogaster, we performed Hi-C and poly(A)+ RNA-seq in four cell lines of various origins (S2, Kc167, DmBG3-c2, and OSC). Contrary to previous studies, we find that regions between TADs (i.e., the inter-TADs and TAD boundaries) in Drosophila are only weakly enriched with the insulator protein dCTCF, while another insulator protein Su(Hw) is preferentially present within TADs. However, Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes. Accordingly, we find that binding of insulator proteins dCTCF and Su(Hw) predicts TAD boundaries much worse than active chromatin marks do. Interestingly, inter-TADs correspond to decompacted inter-bands of polytene chromosomes, whereas TADs mostly correspond to densely packed bands. Collectively, our results suggest that TADs are condensed chromatin domains depleted in active chromatin marks, separated by regions of active chromatin. We propose the mechanism of TAD self-assembly based on the ability of nucleosomes from inactive chromatin to aggregate, and lack of this ability in acetylated nucleosomal arrays. Finally, we test this hypothesis by polymer simulations and find that TAD partitioning may be explained by different modes of inter-nucleosomal interactions for active and inactive chromatin. PMID:26518482

  6. Active chromatin and transcription play a key role in chromosome partitioning into topologically associating domains.

    PubMed

    Ulianov, Sergey V; Khrameeva, Ekaterina E; Gavrilov, Alexey A; Flyamer, Ilya M; Kos, Pavel; Mikhaleva, Elena A; Penin, Aleksey A; Logacheva, Maria D; Imakaev, Maxim V; Chertovich, Alexander; Gelfand, Mikhail S; Shevelyov, Yuri Y; Razin, Sergey V

    2016-01-01

    Recent advances enabled by the Hi-C technique have unraveled many principles of chromosomal folding that were subsequently linked to disease and gene regulation. In particular, Hi-C revealed that chromosomes of animals are organized into topologically associating domains (TADs), evolutionary conserved compact chromatin domains that influence gene expression. Mechanisms that underlie partitioning of the genome into TADs remain poorly understood. To explore principles of TAD folding in Drosophila melanogaster, we performed Hi-C and poly(A)(+) RNA-seq in four cell lines of various origins (S2, Kc167, DmBG3-c2, and OSC). Contrary to previous studies, we find that regions between TADs (i.e., the inter-TADs and TAD boundaries) in Drosophila are only weakly enriched with the insulator protein dCTCF, while another insulator protein Su(Hw) is preferentially present within TADs. However, Drosophila inter-TADs harbor active chromatin and constitutively transcribed (housekeeping) genes. Accordingly, we find that binding of insulator proteins dCTCF and Su(Hw) predicts TAD boundaries much worse than active chromatin marks do. Interestingly, inter-TADs correspond to decompacted inter-bands of polytene chromosomes, whereas TADs mostly correspond to densely packed bands. Collectively, our results suggest that TADs are condensed chromatin domains depleted in active chromatin marks, separated by regions of active chromatin. We propose the mechanism of TAD self-assembly based on the ability of nucleosomes from inactive chromatin to aggregate, and lack of this ability in acetylated nucleosomal arrays. Finally, we test this hypothesis by polymer simulations and find that TAD partitioning may be explained by different modes of inter-nucleosomal interactions for active and inactive chromatin.

  7. Variation in key genes of serotonin and norepinephrine function predicts gamma-band activity during goal-directed attention.

    PubMed

    Enge, Sören; Fleischhauer, Monika; Lesch, Klaus-Peter; Reif, Andreas; Strobel, Alexander

    2014-05-01

    Recent evidence shows that genetic variations in key regulators of serotonergic (5-HT) signaling explain variance in executive tasks, which suggests modulatory actions of 5-HT on goal-directed selective attention as one possible underlying mechanism. To investigate this link, 130 volunteers were genotyped for the 5-HT transporter gene-linked polymorphic region (5-HTTLPR) and for a variation (TPH2-703 G/T) of the TPH2 gene coding for the rate-limiting enzyme of 5-HT synthesis in the brain. Additionally, a functional polymorphism of the norepinephrine transporter gene (NET -3081 A/T) was considered, which was recently found to predict attention and working memory processes in interaction with serotonergic genes. The flanker-based Attention Network Test was used to assess goal-directed attention and the efficiency of attentional networks. Event-related gamma-band activity served to indicate selective attention at the intermediate phenotype level. The main findings were that 5-HTTLPR s allele and TPH2 G-allele homozygotes showed increased induced gamma-band activity during target processing when combined with the NET A/A genotype compared with other genotype combinations, and that gamma activity mediates the genotype-specific effects on task performance. The results further support a modulatory role of 5-HT and NE function in the top-down attentional selection of motivationally relevant over competing or irrelevant sensory input.

  8. SolarSyngas: Results from a virtual institute developing materials and key components for solar thermochemical fuel production

    NASA Astrophysics Data System (ADS)

    Roeb, Martin; Steinfeld, Aldo; Borchardt, Günter; Feldmann, Claus; Schmücker, Martin; Sattler, Christian; Pitz-Paal, Robert

    2016-05-01

    The Helmholtz Virtual Institute (VI) SolarSynGas brings together expertise from solar energy research and materials science to develop metal oxide based redox materials and to integrate them in a suitable way into related process technologies for two-step thermochemical production of hydrogen and carbon monoxide from water and CO2. One of the foci of experimental investigation was exploring the impact of doping on the feasibility of ceria-based materials - mainly by Zr-doping. The results indicate that a certain Zr-content enhances the reducibility and therefore the splitting performance. Increasing the Zr-content to x = 0.15 improved the specific CO2-splitting performance by 50% compared to pure ceria. This finding agrees with theoretical studies attributing the improvements to lattice modification caused by the introduction of Zr4+. Thermogravimetric relaxation experiments and equilibrium oxygen isotope exchange experiments with subsequent depth profiling analysis were carried out on ceria. As a result the reduction reaction of even dense samples of pure ceria with a grain size of about 20 µm is surface reaction controlled. The structure of the derived expression for the apparent activation energy suggests that the chemical surface exchange coefficient should show only a very weak dependence on temperature for ceria doped with lower valence cations. A solar receiver reactor exhibiting a foam-type reticulated porous ceramics made of ceria was tested. It could be shown that applying dual-scale porosity to those foams with mm-size pores for effective radiative heat transfer during reduction and μm-size pores within its struts for enhanced kinetics during oxidation allows enhancing the performance of the reactor significantly. Also a particle process concept applying solid-solid heat recovery from redox particles in a high temperature solar thermochemical process was analysed that uses ceramic spheres as solid heat transfer medium. This concept can be implemented

  9. [Integrated sustainability-oriented reporting--key indicators for communities and cities. Results of a research and development project].

    PubMed

    Süss, W; Glismann, W; Trojan, A

    2005-02-01

    In our research project -- supported by the German Federal Ministry for Education and Research (BMBF) - 35 key indicators were developed in an ongoing process in co-operation with 10 East German cities, which are all members in the German cities healthy network. With these indicators the cities should take up integrated sustainability - oriented health reporting, from which actions and projects for health promotion and prevention can be derived. The conceptual background for the research project and the reports to be made by the project in co-operation with the cities, are the three policy programmes that to be realised on a county level: Healthy Cities, Local Agenda 21 and the German city development programme "Soziale Stadt (socially oriented city)". The common goal of these programmes is the sustainable improvement of the quality of life in the counties. The project is part of the BMBF-supported research field "problem - oriented regional reporting systems", in which other projects are involved which are mainly being conducted in the newly-formed East German "Lander". In this article we describe the co-operative process of the development of the indicators. A synopsis of already applied or proposed sets of indicators for municipal reporting was the basis for the development of the project's set of 35 key indicators. The set of indicators is presented according to its usefulness for planning and realisation of actions for health promotion on county level. For each of the 35 indicators a meta - data description was made to support the counties and cities in our project for health reporting. These indicator profiles are also helpful and supportive for all counties and citiesaiming at such health reporting. The project started in May 2002 and lasts till Mai 2005, so that most reports should be completed in the spring of 2005.

  10. Lipophilicity is a key factor to increase the antiviral activity of HIV neutralizing antibodies.

    PubMed

    Augusto, Marcelo T; Hollmann, Axel; Troise, Fulvia; Veiga, Ana S; Pessi, Antonello; Santos, Nuno C

    2017-04-01

    The HIV broadly neutralizing antibody 2F5 targets the transiently exposed epitope in the membrane proximal external region (MPER) of HIV-1 gp41, by a two-step mechanism involving the viral membrane and this viral glycoprotein. It was recently shown that 2F5 conjugation with a cholesterol moiety outside of the antibody paratope substantially increases its antiviral activity. Additionally, the antiviral activity of D5, a human antibody that binds to the N-terminal heptad repeat (NHR) of gp41 and lacks membrane binding, was boosted by the same cholesterol conjugation. In this work, we evaluated the membrane affinity of both antibodies towards membranes of different compositions, using surface plasmon resonance. A correlation was found between membrane affinity and antiviral activity against HIV-1. We propose that the conjugation of cholesterol to 2F5 or D5 allows a higher degree of antibody pre-concentration at the viral membrane. This way, the antibodies become more available to bind efficiently to the gp41 epitope, blocking viral fusion faster than the unconjugated antibody. These results set up a relevant strategy to improve the rational design of therapeutic antibodies against HIV.

  11. Key Issues in the Role of Peroxisome Proliferator–Activated Receptor Agonism and Cell Signaling in Trichloroethylene Toxicity

    PubMed Central

    Keshava, Nagalakshmi; Caldwell, Jane C.

    2006-01-01

    Peroxisome proliferator–activated receptor α (PPARα) is thought to be involved in several different diseases, toxic responses, and receptor pathways. The U.S. Environmental Protection Agency 2001 draft trichloroethylene (TCE) risk assessment concluded that although PPAR may play a role in liver tumor induction, the role of its activation and the sequence of subsequent events important to tumorigenesis are not well defined, particularly because of uncertainties concerning the extraperoxisomal effects. In this article, which is part of a mini-monograph on key issues in the health risk assessment of TCE, we summarize some of the scientific literature published since that time on the effects and actions of PPARα that help inform and illustrate the key scientific questions relevant to TCE risk assessment. Recent analyses of the role of PPARα in gene expression changes caused by TCE and its metabolites provide only limited data for comparison with other PPARα agonists, particularly given the difficulties in interpreting results involving PPARα knockout mice. Moreover, the increase in data over the last 5 years from the broader literature on PPARα agonists presents a more complex array of extraperoxisomal effects and actions, suggesting the possibility that PPARα may be involved in modes of action (MOAs) not only for liver tumors but also for other effects of TCE and its metabolites. In summary, recent studies support the conclusion that determinations of the human relevance and susceptibility to PPARα-related MOA(s) of TCE-induced effects cannot rely on inferences regarding peroxisome proliferation per se and require a better understanding of the interplay of extraperoxisomal events after PPARα agonism. PMID:16966106

  12. S100A8/A9 activate key genes and pathways in colon tumor progression.

    PubMed

    Ichikawa, Mie; Williams, Roy; Wang, Ling; Vogl, Thomas; Srikrishna, Geetha

    2011-02-01

    The tumor microenvironment plays an important role in modulating tumor progression. Earlier, we showed that S100A8/A9 proteins secreted by myeloid-derived suppressor cells (MDSC) present within tumors and metastatic sites promote an autocrine pathway for accumulation of MDSC. In a mouse model of colitis-associated colon cancer, we also showed that S100A8/A9-positive cells accumulate in all regions of dysplasia and adenoma. Here we present evidence that S100A8/A9 interact with RAGE and carboxylated glycans on colon tumor cells and promote activation of MAPK and NF-κB signaling pathways. Comparison of gene expression profiles of S100A8/A9-activated colon tumor cells versus unactivated cells led us to identify a small cohort of genes upregulated in activated cells, including Cxcl1, Ccl5 and Ccl7, Slc39a10, Lcn2, Zc3h12a, Enpp2, and other genes, whose products promote leukocyte recruitment, angiogenesis, tumor migration, wound healing, and formation of premetastatic niches in distal metastatic organs. Consistent with this observation, in murine colon tumor models we found that chemokines were upregulated in tumors, and elevated in sera of tumor-bearing wild-type mice. Mice lacking S100A9 showed significantly reduced tumor incidence, growth and metastasis, reduced chemokine levels, and reduced infiltration of CD11b(+)Gr1(+) cells within tumors and premetastatic organs. Studies using bone marrow chimeric mice revealed that S100A8/A9 expression on myeloid cells is essential for development of colon tumors. Our results thus reveal a novel role for myeloid-derived S100A8/A9 in activating specific downstream genes associated with tumorigenesis and in promoting tumor growth and metastasis.

  13. Activities of Daily Living in Mexican American Caregivers: The Key to Continuing Informal Care

    PubMed Central

    Evans, Bronwynne C.; Belyea, Michael J.; Coon, David W.; Ume, Ebere

    2013-01-01

    La familia drives elder care in Mexican–American (MA) families, but nursing home placement can result from day-to-day caregiving demands that increase caregiver difficulty with activities of daily living (ADLs). Using life course perspective, this article describes the initial data wave of 31 MA caregivers from a descriptive, longitudinal, mixed-methods study of 110 MA caregivers and care recipients over 15 months in their caregiving trajectories. Fifteen of 31 caregivers consistently indicated “no help needed” on the Katz ADL, whereas all but one reported “help needed” during semistructured interviews with cultural brokers. In addition to the discrepancy between results on the Katz ADL and interviews, findings include consideration of nursing home placement by moderately acculturated caregivers and minimization of their illnesses by caregivers. Additional methods of MA caregiver assessment may be needed due to the questionable accuracy of the Katz ADL; additional research should explore minimization and acculturation in MA caregivers. PMID:22740307

  14. The stellar wind as a key to the understanding of the spectral activity of IN Com

    NASA Astrophysics Data System (ADS)

    Kozlova, O. V.; Alekseev, I. Yu.

    2014-06-01

    We present long-term spectral observations ( R = 20000) of IN Com in the region of the Hα, Hβ, and He I 5876 lines. One distinguishing characteristic of the stellar spectrum is the presence in the Hα line of an extended two-component emission with limits up to ±400 km/s. Emission parameters show the rotation modulation with the stellar rotation period and a significant variability on the long-term scale. Similar emissions are also observed in the Hβ and He I 5876 lines. Our results allow us to conclude that observational emission profiles are formed in an optically thin hot gas. This is a result of the presence of a circumstellar gas disk around IN Com. Its size does not exceed several stellar radii. The material for the disk is supported by the stellar wind from IN Com. The detected variability of Hα-emission parameters shows a clear connection with the photopolarimetric activity of the star. This fact allows us to associate the long-term spectral variability with cycles of stellar activity of IN Com.

  15. Flagellin acting via TLR5 is the major activator of key signaling pathways leading to NF-κB and proinflammatory gene program activation in intestinal epithelial cells

    PubMed Central

    Tallant, Thomas; Deb, Amitabha; Kar, Niladri; Lupica, Joseph; de Veer, Michael J; DiDonato, Joseph A

    2004-01-01

    Background Infection of intestinal epithelial cells by pathogenic Salmonella leads to activation of signaling cascades that ultimately initiate the proinflammatory gene program. The transcription factor NF-κB is a key regulator/activator of this gene program and is potently activated. We explored the mechanism by which Salmonella activates NF-κB during infection of cultured intestinal epithelial cells and found that flagellin produced by the bacteria and contained on them leads to NF-κB activation in all the cells; invasion of cells by the bacteria is not required to activate NF-κB. Results Purified flagellin activated the mitogen activated protein kinase (MAPK), stress-activated protein kinase (SAPK) and Ikappa B kinase (IKK) signaling pathways that lead to expression of the proinflammatory gene program in a temporal fashion nearly identical to that of infection of intestinal epithelial cells by Salmonella. Flagellin expression was required for Salmonella invasion of host cells and it activated NF-κB via toll-like receptor 5 (TLR5). Surprisingly, a number of cell lines found to be unresponsive to flagellin express TLR5 and expression of exogenous TLR5 in these cells induces NF-κB activity in response to flagellin challenge although not robustly. Conversely, overexpression of dominant-negative TLR5 alleles only partially blocks NF-κB activation by flagellin. These observations are consistent with the possibility of either a very stable TLR5 signaling complex, the existence of a low abundance flagellin co-receptor or required adapter, or both. Conclusion These collective results provide the evidence that flagellin acts as the main determinant of Salmonella mediated NF-κB and proinflammatory signaling and gene activation by this flagellated pathogen. In addition, expression of the fli C gene appears to play an important role in the proper functioning of the TTSS since mutants that fail to express fli C are defective in expressing a subset of Sip proteins and

  16. Active Aging Promotion: Results from the Vital Aging Program

    PubMed Central

    Caprara, Mariagiovanna; Molina, María Ángeles; Schettini, Rocío; Santacreu, Marta; Orosa, Teresa; Mendoza-Núñez, Víctor Manuel; Rojas, Macarena; Fernández-Ballesteros, Rocío

    2013-01-01

    Active aging is one of the terms in the semantic network of aging well, together with others such as successful, productive, competent aging. All allude to the new paradigm in gerontology, whereby aging is considered from a positive perspective. Most authors in the field agree active aging is a multidimensional concept, embracing health, physical and cognitive fitness, positive affect and control, social relationships and engagement. This paper describes Vital Aging, an individual active aging promotion program implemented through three modalities: Life, Multimedia, and e-Learning. The program was developed on the basis of extensive evidence about individual determinants of active aging. The different versions of Vital Aging are described, and four evaluation studies (both formative and summative) are reported. Formative evaluation reflected participants' satisfaction and expected changes; summative evaluations yielded some quite encouraging results using quasi-experimental designs: those who took part in the programs increased their physical exercise, significantly improved their diet, reported better memory, had better emotional balance, and enjoyed more cultural, intellectual, affective, and social activities than they did before the course, thus increasing their social relationships. These results are discussed in the context of the common literature within the field and, also, taking into account the limitations of the evaluations accomplished. PMID:23476644

  17. The "10 Keys" to Healthy Aging: 24-Month Follow-Up Results from an Innovative Community-Based Prevention Program

    ERIC Educational Resources Information Center

    Robare, Joseph F.; Bayles, Constance M.; Newman, Anne B.; Williams, Kathy; Milas, Carole; Boudreau, Robert; McTigue, Kathleen; Albert, Steven M.; Taylor, Christopher; Kuller, Lewis H.

    2011-01-01

    The purpose of this report was to evaluate a prevention program to reduce risk factors for common diseases among older individuals in a lower income community. This randomized community-based study enrolled older adults into a Brief Education and Counseling Intervention or a Brief Education and Counseling Intervention plus a physical activity and…

  18. The root iron reductase assay: an examination of key factors that must be respected to generate meaningful assay results

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Plant iron researchers have been quantifying root iron reductase activity since the 1970's, using a simple spectrophotometric method based on the color change of a ferrous iron chromophore. The technique was used by Chaney, Brown, and Tiffin (1972) to demonstrate the obligatory reduction of ferric i...

  19. Cell proliferation is a key determinant of the outcome of FOXO3a activation

    SciTech Connect

    Poulsen, Raewyn C. Carr, Andrew J.; Hulley, Philippa A.

    2015-06-19

    The FOXO family of forkhead transcription factors have a pivotal role in determining cell fate in response to oxidative stress. FOXO activity can either promote cell survival or induce cell death. Increased FOXO-mediated cell death has been implicated in the pathogenesis of degenerative diseases affecting musculoskeletal tissues. The aim of this study was to determine the conditions under which one member of the FOXO family, FOXO3a, promotes cell survival as opposed to cell death. Treatment of primary human tenocytes with 1 pM hydrogen peroxide for 18 h resulted in increased protein levels of FOXO3a. In peroxide-treated cells cultured in low serum media, FOXO3a inhibited cell proliferation and protected against apoptosis. However in peroxide treated cells cultured in high serum media, cell proliferation was unchanged but level of apoptosis significantly increased. Similarly, in tenocytes transduced to over-express FOXO3a, cell proliferation was inhibited and level of apoptosis unchanged in cells cultured in low serum. However there was a robust increase in cell death in FOXO3a-expressing cells cultured in high serum. Inhibition of cell proliferation in either peroxide-treated or FOXO3a-expressing cells cultured in high serum protected against apoptosis induction. Conversely, addition of a Chk2 inhibitor to peroxide-treated or FOXO3a-expressing cells overrode the inhibitory effect of FOXO3a on cell proliferation and led to increased apoptosis in cells cultured in low serum. This study demonstrates that proliferating cells may be particularly susceptible to the apoptosis-inducing actions of FOXO3a. Inhibition of cell proliferation by FOXO3a may be a critical event in allowing the pro-survival rather than the pro-apoptotic activity of FOXO3a to prevail. - Highlights: • FOXO3a activity can result in either promotion of cell survival or apoptosis. • The outcome of FOXO3a activation differs in proliferating compared to non-proliferating cells. • Proliferating

  20. Nitric oxide-mediated cyclooxygenase activation. A key event in the antiplatelet effects of nitrovasodilators.

    PubMed Central

    Salvemini, D; Currie, M G; Mollace, V

    1996-01-01

    We have evaluated the contributions of nitric oxide (NO) and prostacyclin (PGI2) in the in vivo antiplatelet effects of clinically useful nitrovasodilators. In rats, intravenous infusion of three NO donors, glyceryl trinitrate, sodium nitroprusside, or 3'-morpholinosydnonimine, the stable metabolite of molsidomine, released 6-keto PGF1alpha (the stable metabolite of PGI2) and inhibited ex vivo human platelet aggregation to adenosine diphosphate by at least 80%. In in vitro studies, glyceryl trinitrate, sodium nitroprusside, and 3'-morpholinosydnonimine, at clinically attainable concentrations, increased cyclooxygenase activity in endothelial cells (EC), which resulted in a four- to sixfold release of 6-keto PGF1alpha. Pretreatment of the EC with hemoglobin which binds to and inactivates the biological actions of NO, but not by methylene blue (MelB), attenuated the NO-mediated PGI2 from the EC by at least 70%. Release of 6-keto PGF1alpha by the NO donors increased the ability of these compounds to inhibit thrombin-induced human platelet aggregation by at least 10 times; this potentiation was inhibited by hemoglobin but not by MeB. MeB blocked the direct anti-platelet effect of the NO donors in the absence of EC. In summary, we have demonstrated that NO, directly as well as together with an NO-driven cyclooxygenase activation (and hence PGI2), release contributes to the marked anti-platelet effects observed after the in vivo administration of clinically used nitrovasodilators. PMID:8647949

  1. Activation of the immune response is a key feature of aging in mice.

    PubMed

    Brink, Thore C; Regenbrecht, Christian; Demetrius, Lloyd; Lehrach, Hans; Adjaye, James

    2009-12-01

    The process of aging is complex involving numerous factors centered on transcriptional changes with advanced age. This study was aimed at elucidating mechanisms involved in mouse aging by conducting both gene expression and biochemical analyses on isolated mouse brain, heart and kidney. The gene expression analysis was not aimed at solely highlighting age-related transcriptional changes but also revealing regulated biological processes, cellular compartments, signaling and metabolic pathways. We have uncovered a conserved increase in the expression of genes mediating immune responses in all the tissues analyzed. In addition, elevated levels of lipid hydroperoxides (LPO)—an indicator of increased levels of radical oxygen species, implicate an oxidative stress-mediated activity of NF-kB signaling. In summary, these results suggest that transcriptional changes are most probably the downstream effect of environmental and endogenous factors constantly affecting the organism during its lifetime. In addition, we propose LPO as a potential biomarker of aging.

  2. First Results of the TIGRE Chromospheric Activity Survey

    NASA Astrophysics Data System (ADS)

    Mittag, M.; Hempelmann, A.; Gonzalez-Perez, J. N.; Schmitt, J. H. M. M.

    2015-01-01

    We present the first results of the stellar activity survey with TIGRE (Telescopio Internacional de Guanajuato, Robótico-Espectroscópico). This long term program was started in August 2013 with the monitoring of a larger number of stars. We aim at measuring the short- and long-term variability of stellar activity for stars of different spectral types and luminosity classes, using indicators of different spectral lines (mainly Ca II S-Index, Ca II IR triplet, H_α and sodium D). A transformation equation of the TIGRE S-Index into the Mount Wilson S-index was derived in order to compare our results to the vast body of existing S-index measurements. Furthermore, the correlation between the S-index and the lines of the Ca II IR triplet has been studied, based on strictly simultaneous observations.

  3. PDF neuron firing phase-shifts key circadian activity neurons in Drosophila.

    PubMed

    Guo, Fang; Cerullo, Isadora; Chen, Xiao; Rosbash, Michael

    2014-06-17

    Our experiments address two long-standing models for the function of the Drosophila brain circadian network: a dual oscillator model, which emphasizes the primacy of PDF-containing neurons, and a cell-autonomous model for circadian phase adjustment. We identify five different circadian (E) neurons that are a major source of rhythmicity and locomotor activity. Brief firing of PDF cells at different times of day generates a phase response curve (PRC), which mimics a light-mediated PRC and requires PDF receptor expression in the five E neurons. Firing also resembles light by causing TIM degradation in downstream neurons. Unlike light however, firing-mediated phase-shifting is CRY-independent and exploits the E3 ligase component CUL-3 in the early night to degrade TIM. Our results suggest that PDF neurons integrate light information and then modulate the phase of E cell oscillations and behavioral rhythms. The results also explain how fly brain rhythms persist in constant darkness and without CRY.

  4. Human Ebola virus infection results in substantial immune activation.

    PubMed

    McElroy, Anita K; Akondy, Rama S; Davis, Carl W; Ellebedy, Ali H; Mehta, Aneesh K; Kraft, Colleen S; Lyon, G Marshall; Ribner, Bruce S; Varkey, Jay; Sidney, John; Sette, Alessandro; Campbell, Shelley; Ströher, Ute; Damon, Inger; Nichol, Stuart T; Spiropoulou, Christina F; Ahmed, Rafi

    2015-04-14

    Four Ebola patients received care at Emory University Hospital, presenting a unique opportunity to examine the cellular immune responses during acute Ebola virus infection. We found striking activation of both B and T cells in all four patients. Plasmablast frequencies were 10-50% of B cells, compared with less than 1% in healthy individuals. Many of these proliferating plasmablasts were IgG-positive, and this finding coincided with the presence of Ebola virus-specific IgG in the serum. Activated CD4 T cells ranged from 5 to 30%, compared with 1-2% in healthy controls. The most pronounced responses were seen in CD8 T cells, with over 50% of the CD8 T cells expressing markers of activation and proliferation. Taken together, these results suggest that all four patients developed robust immune responses during the acute phase of Ebola virus infection, a finding that would not have been predicted based on our current assumptions about the highly immunosuppressive nature of Ebola virus. Also, quite surprisingly, we found sustained immune activation after the virus was cleared from the plasma, observed most strikingly in the persistence of activated CD8 T cells, even 1 mo after the patients' discharge from the hospital. These results suggest continued antigen stimulation after resolution of the disease. From these convalescent time points, we identified CD4 and CD8 T-cell responses to several Ebola virus proteins, most notably the viral nucleoprotein. Knowledge of the viral proteins targeted by T cells during natural infection should be useful in designing vaccines against Ebola virus.

  5. Reducing conditions are the key for efficient production of active ribonuclease inhibitor in Escherichia coli

    PubMed Central

    2011-01-01

    Background The eukaryotic RNase ribonuclease/angiogenin inhibitors (RI) are a protein group distinguished by a unique structure - they are composed of hydrophobic leucine-rich repeat motifs (LRR) and contain a high amount of reduced cysteine residues. The members of this group are difficult to produce in E. coli and other recombinant hosts due to their high aggregation tendency. Results In this work dithiothreitol (DTT) was successfully applied for improving the yield of correctly folded ribonuclease/angiogenin inhibitor in E. coli K12 periplasmic and cytoplasmic compartments. The feasibility of the in vivo folding concepts for cytoplasmic and periplasmic production were demonstrated at batch and fed-batch cultivation modes in shake flasks and at the bioreactor scale. Firstly, the best secretion conditions of RI in the periplasmic space were evaluated by using a high throughput multifactorial screening approach of a vector library, directly with the Enbase fed-batch production mode in 96-well plates. Secondly, the effect of the redox environment was evaluated in isogenic dsbA+ and dsbA- strains at the various cultivation conditions with reducing agents in the cultivation medium. Despite the fusion to the signal peptide, highest activities were found in the cytoplasmic fraction. Thus by removing the signal peptide the positive effect of the reducing agent DTT was clearly proven also for the cytoplasmic compartment. Finally, optimal periplasmic and cytoplasmic RI fed-batch production processes involving externally added DTT were developed in shake flasks and scaled up to the bioreactor scale. Conclusions DTT highly improved both, periplasmic and cytoplasmic accumulation and activity of RI at low synthesis rate, i.e. in constructs harbouring weak recombinant synthesis rate stipulating genetic elements together with cultivation at low temperature. In a stirred bioreactor environment RI folding was strongly improved by repeated pulse addition of DTT at low aeration

  6. Computational Method for the Systematic Identification of Analog Series and Key Compounds Representing Series and Their Biological Activity Profiles.

    PubMed

    Stumpfe, Dagmar; Dimova, Dilyana; Bajorath, Jürgen

    2016-08-25

    A computational methodology is introduced for detecting all unique series of analogs in large compound data sets, regardless of chemical relationships between analogs. No prior knowledge of core structures or R-groups is required, which are automatically determined. The approach is based upon the generation of retrosynthetic matched molecular pairs and analog networks from which distinct series are isolated. The methodology was applied to systematically extract more than 17 000 distinct series from the ChEMBL database. For comparison, analog series were also isolated from screening compounds and drugs. Known biological activities were mapped to series from ChEMBL, and in more than 13 000 of these series, key compounds were identified that represented substitution sites of all analogs within a series and its complete activity profile. The analog series, key compounds, and activity profiles are made freely available as a resource for medicinal chemistry applications.

  7. Muscle RANK is a key regulator of Ca2+ storage, SERCA activity, and function of fast-twitch skeletal muscles.

    PubMed

    Dufresne, Sébastien S; Dumont, Nicolas A; Boulanger-Piette, Antoine; Fajardo, Val A; Gamu, Daniel; Kake-Guena, Sandrine-Aurélie; David, Rares Ovidiu; Bouchard, Patrice; Lavergne, Éliane; Penninger, Josef M; Pape, Paul C; Tupling, A Russell; Frenette, Jérôme

    2016-04-15

    Receptor-activator of nuclear factor-κB (RANK), its ligand RANKL, and the soluble decoy receptor osteoprotegerin are the key regulators of osteoclast differentiation and bone remodeling. Here we show that RANK is also expressed in fully differentiated myotubes and skeletal muscle. Muscle RANK deletion has inotropic effects in denervated, but not in sham, extensor digitorum longus (EDL) muscles preventing the loss of maximum specific force while promoting muscle atrophy, fatigability, and increased proportion of fast-twitch fibers. In denervated EDL muscles, RANK deletion markedly increased stromal interaction molecule 1 content, a Ca(2+)sensor, and altered activity of the sarco(endo)plasmic reticulum Ca(2+)-ATPase (SERCA) modulating Ca(2+)storage. Muscle RANK deletion had no significant effects on the sham or denervated slow-twitch soleus muscles. These data identify a novel role for RANK as a key regulator of Ca(2+)storage and SERCA activity, ultimately affecting denervated skeletal muscle function.

  8. HIV-1 Nef Impairs Key Functional Activities in Human Macrophages through CD36 Downregulation

    PubMed Central

    Olivetta, Eleonora; Tirelli, Valentina; Chiozzini, Chiara; Scazzocchio, Beatrice; Romano, Ignazio; Arenaccio, Claudia; Sanchez, Massimo

    2014-01-01

    Monocytes and macrophages utilize the class A and B scavenger receptors to recognize and perform phagocytosis of invading microbes before a pathogen-specific immune response is generated. HIV-1 Nef protein affects the innate immune system impairing oxidative burst response and phagocytic capacity of macrophages. Our data show that exogenous recombinant myristoylated Nef protein induces a marked CD36 downregulation in monocytes from Peripheral Blood Mononuclear Cells, in Monocyte-Derived Macrophages (MDMs) differentiated by cytokines and in MDMs contained in a mixed culture obtained expanding PBMCs under Human Erythroid Massive Amplification condition. Under the latter culture condition we identify three main populations after 6 days of expansion: lymphocytes (37.8±14.7%), erythroblasts (46.7±6.1%) and MDMs (15.7±7.5%). The Nef addition to the cell culture significantly downregulates CD36 expression in MDMs, but not in erythroid cells. Furthermore, CD36 inhibition is highly specific since it does not modify the expression levels of other MDM markers such as CD14, CD11c, CD86, CD68, CD206, Toll-like Receptor 2 and Toll-like Receptor 4. Similar results were obtained in MDMs infected with VSV-G pseudotyped HIV-1-expressing Nef. The reduced CD36 membrane expression is associated with decrease of correspondent CD36 mRNA transcript. Furthermore, Nef-induced CD36 downregulation is linked to both impaired scavenger activity with reduced capability to take up oxidized lipoproteins and to significant decreased phagocytosis of fluorescent beads and GFP-expressing Salmonella tiphymurium. In addition we observed that Nef induces TNF-α release in MDMs. Although these data suggest a possible involvement of TNF-α in mediating Nef activity, our results exclude a possible relationship between Nef-induced TNF-α release and Nef-mediated CD36 downregulation. The present work shows that HIV-1 Nef protein may have a role in the strategies elaborated by HIV-1 to alter pathogen

  9. Development of radiometric assays for quantification of enzyme activities of the key enzymes of thyroid hormones metabolism.

    PubMed

    Pavelka, S

    2014-01-01

    We newly elaborated and adapted several radiometric enzyme assays for the determination of activities of the key enzymes engaged in the biosynthesis (thyroid peroxidase, TPO) and metabolic transformations (conjugating enzymes and iodothyronine deiodinases, IDs) of thyroid hormones (THs) in the thyroid gland and in peripheral tissues, especially in white adipose tissue (WAT). We also elaborated novel, reliable radiometric methods for extremely sensitive determination of enzyme activities of IDs of types 1, 2 and 3 in microsomal fractions of different rat and human tissues, as well as in homogenates of cultured mammalian cells. The use of optimized TLC separation of radioactive products from the unconsumed substrates and film-less autoradiography of radiochromatograms, taking advantage of storage phosphor screens, enabled us to determine IDs enzyme activities as low as 10(-18) katals. In studies of the interaction of fluoxetine (Fluox) with the metabolism of THs, we applied adapted radiometric enzyme assays for iodothyronine sulfotransferases (ST) and uridine 5'-diphospho-glucuronyltransferase (UDP-GT). Fluox is the most frequently used representative of a new group of non-tricyclic antidepressant drugs--selective serotonin re-uptake inhibitors. We used the elaborated assays for quantification the effects of Fluox and for the assessment of the degree of potential induction of rat liver ST and/or UDP-GT enzyme activities by Fluox alone or in combination with T(3). Furthermore, we studied possible changes in IDs activities in murine adipose tissue under the conditions that promoted either tissue hypertrophy (obesogenic treatment) or involution (caloric restriction), and in response to leptin, using our newly developed radiometric enzyme assays for IDs. Our results suggest that deiodinase D1 has a functional role in WAT, with D1 possibly being involved in the control of adipose tissue metabolism and/or accumulation of the tissue. Significant positive correlation between

  10. Acidosis is a key regulator of osteoblast ecto-nucleotidase pyrophosphatase/phosphodiesterase 1 (NPP1) expression and activity.

    PubMed

    Orriss, Isabel R; Key, Michelle L; Hajjawi, Mark O R; Millán, José L; Arnett, Timothy R

    2015-12-01

    Previous work has shown that acidosis prevents bone nodule formation by osteoblasts in vitro by inhibiting mineralisation of the collagenous matrix. The ratio of phosphate (Pi ) to pyrophosphate (PPi ) in the bone microenvironment is a fundamental regulator of bone mineralisation. Both Pi and PPi , a potent inhibitor of mineralisation, are generated from extracellular nucleotides by the actions of ecto-nucleotidases. This study investigated the expression and activity of ecto-nucleotidases by osteoblasts under normal and acid conditions. We found that osteoblasts express mRNA for a number of ecto-nucleotidases including NTPdase 1-6 (ecto-nucleoside triphosphate diphosphohydrolase) and NPP1-3 (ecto-nucleotide pyrophosphatase/phosphodiesterase). The rank order of mRNA expression in differentiating rat osteoblasts (day 7) was Enpp1 > NTPdase 4 > NTPdase 6 > NTPdase 5 >  alkaline phosphatase > ecto-5-nucleotidase > Enpp3 > NTPdase 1 > NTPdase 3 > Enpp2 > NTPdase 2. Acidosis (pH 6.9) upregulated NPP1 mRNA (2.8-fold) and protein expression at all stages of osteoblast differentiation compared to physiological pH (pH 7.4); expression of other ecto-nucleotidases was unaffected. Furthermore, total NPP activity was increased up to 53% in osteoblasts cultured in acid conditions (P < 0.001). Release of ATP, one of the key substrates for NPP1, from osteoblasts, was unaffected by acidosis. Further studies showed that mineralised bone formation by osteoblasts cultured from NPP1 knockout mice was increased compared with wildtypes (2.5-fold, P < 0.001) and was partially resistant to the inhibitory effect of acidosis. These results indicate that increased NPP1 expression and activity might contribute to the decreased mineralisation observed when osteoblasts are exposed to acid conditions.

  11. Structural effects of nucleobase variations at key active site residue Ade38 in the hairpin ribozyme

    PubMed Central

    MacElrevey, Celeste; Salter, Jason D.; Krucinska, Jolanta; Wedekind, Joseph E.

    2008-01-01

    The hairpin ribozyme requires functional groups from Ade38 to achieve efficient bond cleavage or ligation. To identify molecular features that contribute to catalysis, structures of position 38 base variants 2,6-diaminopurine (DAP), 2-aminopurine (AP), cytosine (Cyt), and guanine (Gua) were determined between 2.2 and 2.8 Å resolution. For each variant, two substrate modifications were compared: (1) a 2′-O-methyl-substituent at Ade-1 was used in lieu of the nucleophile to mimic the precatalytic state, and (2) a 3′-deoxy-2′,5′-phosphodiester linkage between Ade-1 and Gua+1 was used to mimic a reaction-intermediate conformation. While the global fold of each variant remained intact, the results revealed the importance of Ade38 N1 and N6 groups. Absence of N6 resulting from AP38 coincided with failure to localize the precatalytic scissile phosphate. Cyt38 severely impaired catalysis in a prior study, and its structures here indicated an anti base conformation that sequesters the imino moiety from the scissile bond. Gua38 was shown to be even more deleterious to activity. Although the precatalytic structure was nominally affected, the reaction-intermediate conformation indicated a severe electrostatic clash between the Gua38 keto oxygen and the pro-Rp oxygen of the scissile bond. Overall, position 38 modifications solved in the presence of 2′-OMe Ade-1 deviated from in-line geometry, whereas variants with a 2′,5′ linkage exhibited S-turn destabilization, as well as base conformational changes from syn to anti. These findings demonstrate the importance of the Ade38 Watson–Crick face in attaining a reaction-intermediate state and the sensitivity of the RNA fold to restructuring when electrostatic and shape features fail to complement. PMID:18596253

  12. Power Beamed Photon Sails: New Capabilities Resulting From Recent Maturation Of Key Solar Sail And High Power Laser Technologies

    SciTech Connect

    Montgomery, Edward E. IV

    2010-05-06

    This paper revisits some content in the First International Symposium on Beamed Energy Propulsion in 2002 related to the concept of propellantless in-space propulsion utilizing an external high energy laser to provide momentum to an ultralightweight (gossamer) spacecraft. The design and construction of the NanoSail-D solar sail demonstration spacecraft has demonstrated in space flight hardware the concept of small, very light--yet capable--spacecraft. The results of the Joint High Power Solid State Laser (JHPSSL) have also increased the effectiveness and reduced the cost of an entry level laser source. This paper identifies the impact from improved system parameters on current mission applications.

  13. DIPPER project 871 determination of ideal-gas enthalpies of formation for key compounds, The 1991 project results

    SciTech Connect

    Steele, W.V.; Chirico, R.D.; Knipmeyer, S.E.; Nguyen, A.; Tasker, I.R.

    1993-09-01

    Results of a study aimed at improving group-contribution methodology for estimating thermodynamic properties of organic substances are reported. Specific weaknesses where particular group-contribution terms were unknown, or estimated because of lack of experimental data, are addressed by experimental studies of enthalpies of combustion in condensed phase, vapor-pressure measurements, and differential scanning calorimetric (d.s.c.) heat-capacity measurements. Ideal-gas enthalpies of formation of cyclohexene, phthalan (2,5-dihydrobenzo-3,4-furan), isoxazole, n-octylamine, di-n-octylamine, tri-n-octylamine, phenyl isocyanate, and 1,4,5,6-tetrahydropyrimidine are reported. Two-phase (liquid + vapor) heat capacities were determined for phthalan, isoxazole, the three octylamines, and phenyl isocyanate. Liquid-phase densities along the saturation line were measured for phthalan and isoxazole at 298 to 425 K. The critical temperature and critical density of n-octylamine were determined from d.s.c. results and critical pressure derived from the fitting procedures. Fitting procedures were used to derive critical temperatures, pressures, and densities for cyclohexene (pressure and density only), phthalan, isoxazole, di-n-octylamine, and phenyl isocyanate. Group-additivity parameters or ring-correction terms are derived.

  14. Physical Activity in Child-Care Centers: Do Teachers Hold the Key to the Playground?

    ERIC Educational Resources Information Center

    Copeland, Kristen A.; Kendeigh, Cassandra A.; Saelens, Brian E.; Kalkwarf, Heidi J.; Sherman, Susan N.

    2012-01-01

    Many (56%) US children aged 3-5 years are in center-based childcare and are not obtaining recommended levels of physical activity. In order to determine what child-care teachers/providers perceived as benefits and barriers to children's physical activity in child-care centers, we conducted nine focus groups and 13 one-on-one interviews with 49…

  15. p38 MAPK Is Activated but Does Not Play a Key Role during Apoptosis Induction by Saturated Fatty Acid in Human Pancreatic β-Cells

    PubMed Central

    Šrámek, Jan; Němcová-Fürstová, Vlasta; Balušíková, Kamila; Daniel, Petr; Jelínek, Michael; James, Roger F.; Kovář, Jan

    2016-01-01

    Saturated stearic acid (SA) induces apoptosis in the human pancreatic β-cells NES2Y. However, the molecular mechanisms involved are unclear. We showed that apoptosis-inducing concentrations of SA activate the p38 MAPK signaling pathway in these cells. Therefore, we tested the role of p38 MAPK signaling pathway activation in apoptosis induction by SA in NES2Y cells. Crosstalk between p38 MAPK pathway activation and accompanying ERK pathway inhibition after SA application was also tested. The inhibition of p38 MAPK expression by siRNA silencing resulted in a decrease in MAPKAPK-2 activation after SA application, but it had no significant effect on cell viability or the level of phosphorylated ERK pathway members. The inhibition of p38 MAPK activity by the specific inhibitor SB202190 resulted in inhibition of MAPKAPK-2 activation and noticeable activation of ERK pathway members after SA treatment but in no significant effect on cell viability. p38 MAPK overexpression by plasmid transfection produced an increase in MAPKAPK-2 activation after SA exposure but no significant influence on cell viability or ERK pathway activation. The activation of p38 MAPK by the specific activator anisomycin resulted in significant activation of MAPKAPK-2. Concerning the effect on cell viability, application of the activator led to apoptosis induction similar to application of SA (PARP cleavage and caspase-7, -8, and -9 activation) and in inhibition of ERK pathway members. We demonstrated that apoptosis-inducing concentrations of SA activate the p38 MAPK signaling pathway and that this activation could be involved in apoptosis induction by SA in the human pancreatic β-cells NES2Y. However, this involvement does not seem to play a key role. Crosstalk between p38 MAPK pathway activation and ERK pathway inhibition in NES2Y cells seems likely. Thus, the ERK pathway inhibition by p38 MAPK activation does not also seem to be essential for SA-induced apoptosis. PMID:26861294

  16. Continuum Level Results from Particle Simulations of Active Suspensions

    NASA Astrophysics Data System (ADS)

    Delmotte, Blaise; Climent, Eric; Plouraboue, Franck; Keaveny, Eric

    2014-11-01

    Accurately simulating active suspensions on the lab scale is a technical challenge. It requires considering large numbers of interacting swimmers with well described hydrodynamics in order to obtain representative and reliable statistics of suspension properties. We have developed a computationally scalable model based on an extension of the Force Coupling Method (FCM) to active particles. This tool can handle the many-body hydrodynamic interactions between O (105) swimmers while also accounting for finite-size effects, steady or time-dependent strokes, or variable swimmer aspect ratio. Results from our simulations of steady-stroke microswimmer suspensions coincide with those given by continuum models, but, in certain cases, we observe collective dynamics that these models do not predict. We provide robust statistics of resulting distributions and accurately characterize the growth rates of these instabilities. In addition, we explore the effect of the time-dependent stroke on the suspension properties, comparing with those from the steady-stroke simulations. Authors acknowledge the ANR project Motimo for funding and the Calmip computing centre for technical support.

  17. High Fc Density Particles Result in Binary Complement Activation but Tunable Macrophage Phagocytosis

    NASA Astrophysics Data System (ADS)

    Sulchek, Todd; Pacheco, Patricia; White, David

    2014-03-01

    Macrophage phagocytosis and complement system activation represent two key components of the immune system and both can be activated through the presentation of multiple Fc domains of IgG antibodies. We have created functionalized micro- and nanoparticles with various densities of Fc domains to understand the modulation of the immune system for eventual use as a novel immunomodulation platform. Phagocytosis assays were carried out by adding functionalized particles to macrophage cells and quantitatively determined using fluorescent microscopy and flow cytometry. Complement system activation by the functionalized particles in human serum was quantified with an enzyme immunoassay. Our phagocytosis assay revealed a strong dependence on particle size and Fc density. For small particles, as the Fc density increased, the number of particles phagocytosed also increased. Large particles were phagocytosed at significantly lower levels and showed no dependency on Fc density. Complement was successfully activated at levels comparable to positive controls for small particles at high Fc densities. However at low Fc densities, there is a significant decrease in complement activation. This result suggests a binary response for complement system activation with a threshold density for successful activation. Therefore, varying the Fc density on micro/nanoparticles resulted in a tunable response in macrophage phagocytosis while a more binary response for complement activation.

  18. Differences in activation of aryl hydrocarbon receptors of white sturgeon relative to lake sturgeon are predicted by identities of key amino acids in the ligand binding domain.

    PubMed

    Doering, Jon A; Farmahin, Reza; Wiseman, Steve; Beitel, Shawn C; Kennedy, Sean W; Giesy, John P; Hecker, Markus

    2015-04-07

    Dioxin-like compounds (DLCs) are pollutants of global environmental concern. DLCs elicit their adverse outcomes through activation of the aryl hydrocarbon receptor (AhR). However, there is limited understanding of the mechanisms that result in differences in sensitivity to DLCs among different species of fishes. Understanding these mechanisms is critical for protection of the diversity of fishes exposed to DLCs, including endangered species. This study investigated specific mechanisms that drive responses of two endangered fishes, white sturgeon (Acipenser transmontanus) and lake sturgeon (Acipenser fulvescens) to DLCs. It determined whether differences in sensitivity to activation of AhRs (AhR1 and AhR2) can be predicted based on identities of key amino acids in the ligand binding domain (LBD). White sturgeon were 3- to 30-fold more sensitive than lake sturgeon to exposure to 5 different DLCs based on activation of AhR2. There were no differences in sensitivity between white sturgeon and lake sturgeon based on activation of AhR1. Adverse outcomes as a result of exposure to DLCs have been shown to be mediated through activation of AhR2, but not AhR1, in all fishes studied to date. This indicates that white sturgeon are likely to have greater sensitivity in vivo relative to lake sturgeon. Homology modeling and in silico mutagenesis suggests that differences in sensitivity to activation of AhR2 result from differences in key amino acids at position 388 in the LBD of AhR2 of white sturgeon (Ala-388) and lake sturgeon (Thr-388). This indicates that identities of key amino acids in the LBD of AhR2 could be predictive of both in vitro activation by DLCs and in vivo sensitivity to DLCs in these, and potentially other, fishes.

  19. Receptor Activator for Nuclear Factor kappa B Ligand (RANKL) as an osteoimmune key regulator in bone physiology and pathology.

    PubMed

    Narducci, Paola; Bareggi, Renato; Nicolin, Vanessa

    2011-02-01

    The strength and integrity of the human skeleton depends on a delicate equilibrium between bone resorption and bone formation. Bone resorption is an elementary cellular activity in the modelling of the skeleton during growth and development. Later in life a most important physiological process in the skeleton is bone remodelling, which is locally initiated by resorption. During remodelling bone resorption is coupled to new bone formation that ensures renewal of bone with only minor local and temporary bone loss. Cells responsible for bone resorption and subsequent bone formation are the osteoclasts and osteoblasts, respectively. The osteoclast is derived from the pluripotent hematopoietic stem cell, which gives rise to a myeloid stem cell that can further differentiate into megakaryocytes, granulocytes, monocytes/macrophages and osteoclasts. The respective bone resorbing and forming actions of osteoclasts and osteoblasts are finely coupled, so that bone mass remains remarkably stable in a healthy adult. Imbalance between osteoclast and osteoblast activities can arise from a wide variety of hormonal changes or perturbations of inflammatory and growth factors resulting in postmenopausal osteoporosis, Paget's disease, lytic bone metastases, or rheumatoid arthritis, leading to increased bone resorption and crippling bone damage. In view of the critical role of osteoclasts in diverse pathology, there has been immense effort aimed at understanding the biology of this unique cell. The present review is focused on the current knowledge of the mechanisms that regulate the functional links between bone turnover and the immune system helping us to understand the main factors that lead to bone loss observed in osteoporosis, cancer and in rheumatoid arthritis. The aim of this review paper is to consider the key molecular interactions involved in the formation of osteoclast cells in normal and pathological conditions.

  20. Disk-driven hydromagnetic winds as a key ingredient of active galactic nuclei unification schemes

    NASA Technical Reports Server (NTRS)

    Konigl, Arieh; Kartje, John F.

    1994-01-01

    Centrifugally driven winds from the surfaces of magnetized accretion disks have been recognized as an attractive mechanism of removing the angular momentum of the accreted matter and of producing the bipolar outflows and jets that are often associated with compact astronomical objects. As previously suggested in the context of young stellar objects, such winds have unique observational manifestations stemming from their highly stratified density and velocity structure and from their exposure to the strong continuum radiation field of the compact object. We have applied this scenario to active galactic nuclei (AGNs) and investigated the properties of hydromagnetic outflows that originate within approximately 10(M(sub 8)) pc of the central 10(exp 8)(M(sub 8)) solar mass black hole. On the basis of our results, we propose that hydromagnetic disk-driven winds may underlie the classification of broad-line and narrow-line AGNs (e.g., the Seyfert 1/Seyfert 2 dichotomy) as well as the apparent dearth of luminous Seyfert 2 galaxies. More generally, we demonstrate that such winds could strongly influence the spectral characteristics of Seyfert galaxies, QSOs, and BL Lac objects (BLOs). In our picture, the torus is identified with the outer regions of the wind where dust uplifted from the disk surfaces by gas-grain collisions is embedded in the outflow. Using an efficient radiative transfer code, we show that the infrared emission of Seyfert galaxies and QSOs can be attributed to the reprocessing of the UV/soft X-ray AGN continuum by the dust in the wind and the disk. We demonstrate that the radiation pressure force flattens the dust distribution in objects with comparatively high (but possibly sub-Eddington) bolometric luminosities, and we propose this as one likely reason for the apparent paucity of narrow-line objects among certain high-luminosity AGNs. Using the XSTAR photoionization code, we show that the inner regions of the wind could naturally account for the warm

  1. Key mediators of intracellular amino acids signaling to mTORC1 activation.

    PubMed

    Duan, Yehui; Li, Fengna; Tan, Kunrong; Liu, Hongnan; Li, Yinghui; Liu, Yingying; Kong, Xiangfeng; Tang, Yulong; Wu, Guoyao; Yin, Yulong

    2015-05-01

    Mammalian target of rapamycin complex 1 (mTORC1) is activated by amino acids to promote cell growth via protein synthesis. Specifically, Ras-related guanosine triphosphatases (Rag GTPases) are activated by amino acids, and then translocate mTORC1 to the surface of late endosomes and lysosomes. Ras homolog enriched in brain (Rheb) resides on this surface and directly activates mTORC1. Apart from the presence of intracellular amino acids, Rag GTPases and Rheb, other mediators involved in intracellular amino acid signaling to mTORC1 activation include human vacuolar sorting protein-34 (hVps34) and mitogen-activating protein kinase kinase kinase kinase-3 (MAP4K3). Those molecular links between mTORC1 and its mediators form a complicate signaling network that controls cellular growth, proliferation, and metabolism. Moreover, it is speculated that amino acid signaling to mTORC1 may start from the lysosomal lumen. In this review, we discussed the function of these mediators in mTORC1 pathway and how these mediators are regulated by amino acids in details.

  2. Prediction of Geomagnetic Activity and Key Parameters in High-latitude Ionosphere

    NASA Technical Reports Server (NTRS)

    Khazanov, George V.; Lyatsky, Wladislaw; Tan, Arjun; Ridley, Aaron

    2007-01-01

    Prediction of geomagnetic activity and related events in the Earth's magnetosphere and ionosphere are important tasks of US Space Weather Program. Prediction reliability is dependent on the prediction method, and elements included in the prediction scheme. Two of the main elements of such prediction scheme are: an appropriate geomagnetic activity index, and an appropriate coupling function (the combination of solar wind parameters providing the best correlation between upstream solar wind data and geomagnetic activity). We have developed a new index of geomagnetic activity, the Polar Magnetic (PM) index and an improved version of solar wind coupling function. PM index is similar to the existing polar cap PC index but it shows much better correlation with upstream solar wind/IMF data and other events in the magnetosphere and ionosphere. We investigate the correlation of PM index with upstream solar wind/IMF data for 10 years (1995-2004) that include both low and high solar activity. We also have introduced a new prediction function for the predicting of cross-polar-cap voltage and Joule heating based on using both PM index and upstream solar wind/IMF data. As we show such prediction function significantly increase the reliability of prediction of these important parameters. The correlation coefficients between the actual and predicted values of these parameters are approx. 0.9 and higher.

  3. Florida Keys

    NASA Technical Reports Server (NTRS)

    2002-01-01

    The Florida Keys are a chain of islands, islets and reefs extending from Virginia Key to the Dry Tortugas for about 309 kilometers (192 miles). The keys are chiefly limestone and coral formations. The larger islands of the group are Key West (with its airport), Key Largo, Sugarloaf Key, and Boca Chica Key. A causeway extends from the mainland to Key West.

    This image was acquired on October 28, 2001, by the Advanced Spaceborne Thermal Emission and Reflection Radiometer (ASTER) on NASA's Terra satellite. With its 14 spectral bands from the visible to the thermal infrared wavelength region, and its high spatial resolution of 15 to 90 meters (about 50 to 300 feet), ASTER images Earth to map and monitor the changing surface of our planet.

    ASTER is one of five Earth-observing instruments launched December 18, 1999, on NASA's Terra satellite. The instrument was built by Japan's Ministry of Economy, Trade and Industry. A joint U.S./Japan science team is responsible for validation and calibration of the instrument and the data products.

    The broad spectral coverage and high spectral resolution of ASTER will provide scientists in numerous disciplines with critical information for surface mapping, and monitoring of dynamic conditions and temporal change. Example applications are: monitoring glacial advances and retreats; monitoring potentially active volcanoes; identifying crop stress; determining cloud morphology and physical properties; wetlands evaluation; thermal pollution monitoring; coral reef degradation; surface temperature mapping of soils and geology; and measuring surface heat balance.

    Dr. Anne Kahle at NASA's Jet Propulsion Laboratory, Pasadena, Calif., is the U.S. Science team leader; Bjorn Eng of JPL is the project manager. The Terra mission is part of NASA's Earth Science Enterprise, a long- term research effort to understand and protect our home planet. Through the study of Earth, NASA will help to provide sound science to policy and economic

  4. Active Spacecraft Potential Control: Results From the Double Star Project

    NASA Astrophysics Data System (ADS)

    Torkar, K.; Fazakerley, A.; Steiger, W.

    2006-10-01

    The ion emitter instrument "active spacecraft potential control" (ASPOC) has been used successfully in several magnetospheric missions including the European Space Agency Cluster Project. An improved version has been developed for the equatorial spacecraft of the Chinese-European Double Star mission (TC-1) launched in December 2003. The modifications include a new design of the ion emitter modules. As a result, higher currents than in previous missions can be achieved. The main objective of the investigation is the reduction of positive spacecraft potential in order to minimize perturbations to the plasma measurements onboard, in particular to the plasma electron instrument PEACE. These data show an almost complete suppression of photoelectrons when ASPOC is emitting at 30- to 50-muA beam current. The angular distribution of the electrons in the presence of the ion beam is investigated in detail. The measurement of ambient electron distributions is highly improved.

  5. Cues Resulting in Desire for Sexual Activity in Women

    PubMed Central

    McCall, Katie; Meston, Cindy

    2010-01-01

    Introduction A number of questionnaires have been created to assess levels of sexual desire in women, but to our knowledge, there are currently no validated measures for assessing cues that result in sexual desire. A questionnaire of this nature could be useful for both clinicians and researchers, because it considers the contextual nature of sexual desire and it draws attention to individual differences in factors that can contribute to sexual desire. Aim The aim of the present study was to create a multidimensional assessment tool of cues for sexual desire in women that is validated in women with and without hypoactive sexual desire disorder (HSDD). Methods Factor analyses conducted on both an initial sample (N = 874) and a community sample (N = 138) resulted in the Cues for Sexual Desire Scale (CSDS) which included four factors: (i) Emotional Bonding Cues; (ii) Erotic/ Explicit Cues; (iii) Visual/Proximity Cues; and (iv) Implicit/Romantic Cues. Main Outcome Measures Scale construction of cues associated with sexual desire and differences between women with and without sexual dysfunction. Results The CSDS demonstrated good reliability and validity and was able to detect significant differences between women with and without HSDD. Results from regression analyses indicated that both marital status and level of sexual functioning predicted scores on the CSDS. The CSDS provided predictive validity for the Female Sexual Function Index desire and arousal domain scores, and increased cues were related to a higher reported frequency of sexual activity in women. Conclusions The findings from the present study provide valuable information regarding both internal and external triggers that can result in sexual desire for women. We believe that the CSDS could be beneficial in therapeutic settings to help identify cues that do and do not facilitate sexual desire in women with clinically diagnosed desire difficulties. PMID:16942529

  6. Behavioral science in video games for children's diet and physical activity change: Key research needs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Innovative intervention programs are needed to overcome the limitations in previous programs that promoted change in diabetes risk behaviors in children. Serious video games show promise of changing dietary and physical activity behaviors, but research is needed on the optimal design of behavior-cha...

  7. Enjoyment Fosters Engagement: The Key to Involving Middle School Students in Physical Education and Physical Activity

    ERIC Educational Resources Information Center

    Pharez, Emily S.

    2016-01-01

    This article describes the challenges faced by a middle school teacher who inherited a recreation-based physical education program in which students had been accustomed to choosing what they wanted to do. Stressing the importance of implementing a standards-based program in which students of all skill levels and activity preferences were able to…

  8. Collaboration with aviation — The key to commercialisation of space activities

    NASA Astrophysics Data System (ADS)

    Collins, Patrick; Funatsu, Yoshiyuki

    2000-07-01

    The US government's Commercial Space Act of 1998 and commitment to commercialise the International Space Station's operations have changed the direction of space development in the post-cold-war world definitively. During 1998 also the feasibility and great economic potential of space travel by the general public was acknowledged in publications by NASA, AIAA and the Japanese Keidanren. However, crewed space activities are all taxpayer-funded, primarily for scientific research; they have involved only a few hundred people traveling to space to date; and those involved have no experience of commercial passenger service operations. By contrast, aviation is a global industry, largely commercial, involving the range of activities from engineering design to marketing, and serving more than 1 billion passengers/year. Aviation has very high safety levels developed over decades of experience of carrying billions of passengers. Furthermore, the aviation industry also has extensive experience of operating rocket-powered piloted vehicles: during the 1950s several countries operated such vehicles sufficiently frequently to develop routine operations, maintenance and repair procedures. Consequently, in order to develop safe and profitable passenger travel services to, from and in space, people, companies and organisations with experience of space activities have a great deal to gain from collaboration with all parts of the aviation industry. Due to the potential economic value of this development, and the high cost to taxpayers of space activities today, governments should take steps to start this collaboration as soon as possible.

  9. Physical activity in child-care centers: do teachers hold the key to the playground?

    PubMed Central

    Copeland, Kristen A.; Kendeigh, Cassandra A.; Saelens, Brian E.; Kalkwarf, Heidi J.; Sherman, Susan N.

    2012-01-01

    Many (56%) US children aged 3–5 years are in center-based childcare and are not obtaining recommended levels of physical activity. In order to determine what child-care teachers/providers perceived as benefits and barriers to children’s physical activity in child-care centers, we conducted nine focus groups and 13 one-on-one interviews with 49 child-care teachers/providers in Cincinnati, OH. Participants noted physical and socio-emotional benefits of physical activity particular to preschoolers (e.g. gross motor skill development, self-confidence after mastery of new skills and improved mood, attention and napping after exercise) but also noted several barriers including their own personal attitudes (e.g. low self-efficacy) and preferences to avoid the outdoors (e.g. don’t like hot/cold weather, getting dirty, chaos of playground). Because individual teachers determine daily schedules and ultimately make the decision whether to take the children outdoors, they serve as gatekeepers to the playground. Participants discussed a spectrum of roles on the playground, from facilitator to chaperone to physical activity inhibitor. These findings suggest that children could have very different gross motor experiences even within the same facility (with presumably the same environment and policies), based on the beliefs, creativity and level of engagement of their teacher. PMID:21804083

  10. Increasing AIP Macrocycle Size Reveals Key Features of agr Activation in Staphylococcus aureus.

    PubMed

    Johnson, Jeffrey G; Wang, Boyuan; Debelouchina, Galia T; Novick, Richard P; Muir, Tom W

    2015-05-04

    The agr locus in the commensal human pathogen, Staphylococcus aureus, is a two-promoter regulon with allelic variability that produces a quorum-sensing circuit involved in regulating virulence within the bacterium. Secretion of unique autoinducing peptides (AIPs) and detection of their concentrations by AgrC, a transmembrane receptor histidine kinase, coordinates local bacterial population density with global changes in gene expression. The finding that staphylococcal virulence can be inhibited through antagonism of this quorum-sensing pathway has fueled tremendous interest in understanding the structure-activity relationships underlying the AIP-AgrC interaction. The defining structural feature of the AIP is a 16-membered, thiolactone-containing macrocycle. Surprisingly, the importance of ring size on agr activation or inhibition has not been explored. In this study, we address this deficiency through the synthesis and functional analysis of AIP analogues featuring enlarged and reduced macrocycles. Notably, this study is the first to interrogate AIP function by using both established cell-based reporter gene assays and newly developed in vitro AgrC-I binding and autophosphorylation activity assays. Based on our data, we present a model for robust agr activation involving a cooperative, three-points-of-contact interaction between the AIP macrocycle and AgrC.

  11. Making Physics Fun: Key Concepts, Classroom Activities, and Everyday Examples, Grades K-8

    ERIC Educational Resources Information Center

    Prigo, Robert

    2007-01-01

    Teaching physical science in the elementary and middle grades can be challenging for busy teachers faced with growing science demands and limited classroom resources. Robert Prigo provides fun and engaging activities using safe, available materials that educators can easily incorporate into lesson plans. Extensive examples, sample inquiry…

  12. The Key Factors of an Active Learning Method in a Microprocessors Course

    ERIC Educational Resources Information Center

    Carpeno, A.; Arriaga, J.; Corredor, J.; Hernandez, J.

    2011-01-01

    The creation of the European Higher Education Area (EHEA) is promoting a change toward a new model of education focused on the student. It is impelling methodological innovation processes in many European universities, leading more teachers to apply methods based on active and cooperative learning in their classrooms. However, the successful…

  13. Key programmatic steps and activities for implementing the Uranium Mill Tailings Remedial Action Project. [UMTRA Project

    SciTech Connect

    Not Available

    1985-07-01

    The Uranium Mill Tailings Radiation Control Act of 1978 (UMTRCA) was enacted based upon findings by Congress that uranium mill tailings located at active and inactive hazard to the public, and that protection of the public health, safety and welfare, and the regulations of interstate commerce, require that every reasonable effort be made to provide for the stabilization, disposal, and control in a safe and environmentally sound manner of such tailings in order to prevent or minimize radon diffusion into the environment and to prevent or minimize other environmental hazards from such tailings.'' A general understanding of the steps leading to elimination of the hazards associated with designated uranium mill tailings sites, and the parties involved in that effort, are presented in this document. A representative schedule is also presented in this document to show both program sequence and activity interdependence. Those activities that have the most potential to influence program duration, because of the significant amount of additional time that may be required, include identification and selection of a suitable site, field data collection delays due to weather, actual acquisition of the designated or alternate disposal site, construction delays due to weather, and site licensing. This document provides an understanding of the steps, the sequence, the parties involved, and a representative duration of activities leading to remedial action and cleanup at the designated inactive uranium mill tailings sites. 10 refs., 5 figs., 1 tab.

  14. Activated macrophages as key mediators of capsule formation on adipose constructs in tissue engineering chamber models.

    PubMed

    Zhan, Weiqing; Lu, Feng

    2017-04-01

    In plastic and reconstructive field, it would be much beneficial to fabricate an engineered adipose tissue substitute allowing reliable and complete fat tissue regeneration. Tissue engineering chamber (TEC) holds the promise to optimize an adipogenic configuration that is efficacious as well as reproducible. A frequently occurring complication involves the adipose tissue flap encapsulation and, effectively, its shielding, by a thick fibrous membrane, which hinders development into the proliferative stage. The reason for the deposition of the collagen capsule remains unclear. Numerous studies have highlighted that macrophages play a key role in adipogenesis in a TEC model using a silicone chamber enclosing the fat flap with a superficial epigastric pedicle. As a verification of the role of macrophages in capsule formation, we propose the inhibition of transforming growth factor β1 (TGF-β1) synthesis by macrophage populations in the local microenvironment by administrating tranilast into the TEC. We hypothesize that upon reduction of TGF-β1 levels, capsule formation and inhibition of new adipose tissue development will decrease. Furthermore, we propose that a tissue engineering chamber model in which macrophages are closely related to both neo-adipogenesis and capsule formation.

  15. KEY COMPARISON: Update of the BIPM comparison BIPM.RI(II)-K1.F-18 of activity measurements of the radionuclide 18F to include the NPL

    NASA Astrophysics Data System (ADS)

    Ratel, G.; Michotte, C.; Woods, M. J.

    2003-01-01

    Since 2001, four national metrology institutes (NMIs) have submitted four samples of known activity of 18F to the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures, the most recent being that of the NPL (UK). The activities ranged from about 1 MBq to 8 MBq. The key comparison reference value (KCRV) has been recalculated to include the latest value and the degrees of equivalence between each equivalent activity measured in the SIR and the key comparison reference value (KCRV) have been calculated and the results are given in the form of a matrix. A graphical presentation is also given. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by Section II of the Consultative Committee for Ionizing Radiation (CCRI(II)), comparison identifier BIPM.RI(II)-K1.F-18, according to the provisions of the Mutual Recognition Arrangement (MRA).

  16. KEY COMPARISON: Update of the BIPM comparison BIPM.RI(II)-K1.F-18 of activity measurements of the radionuclide 18F to include the CIEMAT

    NASA Astrophysics Data System (ADS)

    Ratel, G.; Michotte, C.; García-Toraño, E.; Los Arcos, J.-M.

    2004-01-01

    Since 2001, five national metrology institutes (NMIs) have submitted five samples of known activity of 18F to the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures (BIPM), the most recent being that of the CIEMAT (Spain). The activities ranged from about 1 MBq to 18 MBq. The key comparison reference value (KCRV) has been recalculated to include the latest value and the degrees of equivalence between each equivalent activity measured in the SIR have been calculated and the results are given in the form of a matrix. A graphical presentation is also given for this key comparison with identifier BIPM.RI(II)-K1.F-18. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by Section II of the Consultative Committee for Ionizing Radiation (CCRI(II)), according to the provisions of the Mutual Recognition Arrangement (MRA).

  17. KEY COMPARISON: Update of the BIPM comparison BIPM.RI(II)-K1.F-18 of activity measurements of the radionuclide 18F to include the PTB

    NASA Astrophysics Data System (ADS)

    Ratel, G.; Michotte, C.; Kossert, K.; Janßen, H.

    2006-01-01

    Since 2001, six national metrology institutes (NMIs) have submitted six samples of known activity of 18F to the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures (BIPM), the most recent being that of the PTB (Germany). The activities ranged from about 1 MBq to 18 MBq. The key comparison reference value (KCRV) has been recalculated to include the latest value, with the agreement of the CCRI(II). The degrees of equivalence between each equivalent activity measured in the SIR have been recalculated and the results are given in the form of a matrix. A graphical presentation is also given for this key comparison with identifier BIPM.RI(II)-K1.F-18. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by Section II of the Consultative Committee for Ionizing Radiation (CCRI(II)), according to the provisions of the Mutual Recognition Arrangement (MRA).

  18. [The referral of infectious diseases is a key activity for infectious diseases departments and units, as well as for the hospital].

    PubMed

    Cisneros, José Miguel; Palomino-Nicás, Julián; Pachón-Diaz, Jerónimo

    2014-12-01

    Infectious diseases referrals (IDR) is a core activity of infectious diseases departments, and is certainly the one with the greatest potential impact on the hospital due to their cross-sectional nature, and with the emergence of a bacterial resistance and antimicrobial crisis. However, there is no standard model for IDR, no official training, and evaluation is merely descriptive. Paradoxically IDR are at risk in a health system that demands more quality and efficiency. The aim of this review is to assess what is known about IDR, its definition, key features, objectives, method, and the evaluation of results, and to suggest improvements to this key activity for the infectious diseases departments and the hospital.

  19. PIASxbeta is a key regulator of osterix transcriptional activity and matrix mineralization in osteoblasts.

    PubMed

    Ali, Md Moksed; Yoshizawa, Tatsuya; Ishibashi, Osamu; Matsuda, Akio; Ikegame, Mika; Shimomura, Junko; Mera, Hisashi; Nakashima, Kazuhisa; Kawashima, Hiroyuki

    2007-08-01

    We recently reported that tensile stress induces osteoblast differentiation and osteogenesis in the mouse calvarial suture in vitro. Using this experimental system, we identified PIASxbeta, a splice isoform of Pias2, as one of the genes most highly upregulated by tensile stress. Further study using cell culture revealed that this upregulation was transient and was accompanied by upregulation of other differentiation markers, including osterix, whereas expression of Runx2 was unaffected. Runx2 and osterix are the two master proteins controlling osteoblast differentiation, with Runx2 being upstream of osterix. Targeted knockdown of PIASxbeta by small interfering RNA (siRNA) markedly suppressed osteoblastic differentiation and matrix mineralization, whereas transient overexpression of PIASxbeta caused the exact opposite effects. Regardless of PIASxbeta expression level, Runx2 expression remained constant. Reporter assays demonstrated that osterix enhanced its own promoter activity, which was further stimulated by PIASxbeta but not by its sumoylation-defective mutant. NFATc1 and NFATc3 additionally increased osterix transcriptional activity when co-transfected with PIASxbeta. Because osterix has no consensus motif for sumoylation, other proteins are probably involved in the PIASxbeta-mediated activation and NFAT proteins may be among such targets. This study provides the first line of evidence that PIASxbeta is indispensable for osteoblast differentiation and matrix mineralization, and that this signaling molecule is located between Runx2 and osterix.

  20. Lactic acid bacterial symbionts in honeybees - an unknown key to honey's antimicrobial and therapeutic activities.

    PubMed

    Olofsson, Tobias C; Butler, Èile; Markowicz, Pawel; Lindholm, Christina; Larsson, Lennart; Vásquez, Alejandra

    2016-10-01

    Could honeybees' most valuable contribution to mankind besides pollination services be alternative tools against infections? Today, due to the emerging antibiotic-resistant pathogens, we are facing a new era of searching for alternative tools against infections. Natural products such as honey have been applied against human's infections for millennia without sufficient scientific evidence. A unique lactic acid bacterial (LAB) microbiota was discovered by us, which is in symbiosis with honeybees and present in large amounts in fresh honey across the world. This work investigates if the LAB symbionts are the source to the unknown factors contributing to honey's properties. Hence, we tested the LAB against severe wound pathogens such as methicillin-resistant Staphylococcus aureus (MRSA), Pseudomonas aeruginosa and vancomycin-resistant Enterococcus (VRE) among others. We demonstrate a strong antimicrobial activity from each symbiont and a synergistic effect, which counteracted all the tested pathogens. The mechanisms of action are partly shown by elucidating the production of active compounds such as proteins, fatty acids, anaesthetics, organic acids, volatiles and hydrogen peroxide. We show that the symbionts produce a myriad of active compounds that remain in variable amounts in mature honey. Further studies are now required to investigate if these symbionts have a potential in clinical applications as alternative tools against topical human and animal infections.

  1. Optimal active vibration absorber: Design and experimental results

    NASA Technical Reports Server (NTRS)

    Lee-Glauser, Gina; Juang, Jer-Nan; Sulla, Jeffrey L.

    1992-01-01

    An optimal active vibration absorber can provide guaranteed closed-loop stability and control for large flexible space structures with collocated sensors/actuators. The active vibration absorber is a second-order dynamic system which is designed to suppress any unwanted structural vibration. This can be designed with minimum knowledge of the controlled system. Two methods for optimizing the active vibration absorber parameters are illustrated: minimum resonant amplitude and frequency matched active controllers. The Controls-Structures Interaction Phase-1 Evolutionary Model at NASA LaRC is used to demonstrate the effectiveness of the active vibration absorber for vibration suppression. Performance is compared numerically and experimentally using acceleration feedback.

  2. p38 mitogen-activated protein kinase plays a key role in regulating MAPKAPK2 expression

    SciTech Connect

    Sudo, Tatsuhiko . E-mail: sudo@riken.jp; Kawai, Kayoko; Matsuzaki, Hiroshi; Osada, Hiroyuki

    2005-11-18

    One of three major families of the mitogen-activated kinases (MAPK), p38 as well as JNK, has been shown to transduce extracellular stress stimuli into cellular responses by phospho-relay cascades. Among p38 families, p38{alpha} is a widely characterized isoform and the biological phenomena are explained by its kinase activity regulating functions of its downstream substrates. However, its specific contributions to each phenomenon are yet not fully elucidated. For better understanding of the role of MAPKs, especially p38{alpha}, we utilized newly established mouse fibroblast cell lines originated from a p38{alpha} null mouse, namely, a parental cell line without p38{alpha} gene locus, knockout of p38{alpha} (KOP), Zeosin-resistant (ZKOP), revertant of p38{alpha} (RKOP), and Exip revertant (EKOP). EKOP is smaller in size but grows faster than the others. Although comparable amounts of ERK and JNK are expressed in each cell line, ERK is highly phosphorylated in EKOP even in normal culture conditions. Serum stimulation after serum starvation led to ERK phosphorylation in RKOP and ZKOP, but not in EKOP as much. On the contrary, relative phosphorylation level of JNK to total JNK in response to UV was low in RKOP. And its phosphorylation as well as total JNK is slightly lower in EKOP. RKOP is less sensitive to UV irradiation as judged by the survival rate. Stress response upon UV or sorbitol stimuli, leading to mitogen activate protein kinase activated kinase 2 (MAPKAPK2) phosphorylation, was only observed in RKOP. Further experiments reveal that MAPKAPK2 expression is largely suppressed in ZKOP and EKOP. Its expression was recovered by re-introduction of p38{alpha}. The loss of MAPKAPK2 expression accompanied by the defect of p38{alpha} is confirmed in an embryonic extract prepared from p38{alpha} null mice. These data demonstrate that p38 signal pathway is regulated not only by phosphorylation but also by modulation of the expression of its component. Together, we have

  3. Behavioral science in video games for children's diet and physical activity change: key research needs.

    PubMed

    Baranowski, Tom; Baranowski, Janice; Thompson, Debbe; Buday, Richard

    2011-03-01

    Innovative intervention programs are needed to overcome the limitations in previous programs that promoted change in diabetes risk behaviors in children. Serious video games show promise of changing dietary and physical activity behaviors, but research is needed on the optimal design of behavior-change procedures in video games, the mechanisms that account for changes obtained, and the groups in which these interventions work best. Such research will permit the optimal design of serious video games for diabetes and obesity prevention in the future.

  4. Mitochondrial ClpX activates a key enzyme for heme biosynthesis and erythropoiesis

    PubMed Central

    Kardon, Julia R.; Yien, Yvette Y.; Huston, Nicholas C.; Branco, Diana S.; Hildick-Smith, Gordon J.; Rhee, Kyu Y.; Paw, Barry H.; Baker, Tania A.

    2015-01-01

    SUMMARY The mitochondrion maintains and regulates its proteome with chaperones primarily inherited from its bacterial endosymbiont ancestor. Among these chaperones is the AAA+ unfoldase ClpX, an important regulator of prokaryotic physiology with poorly defined function in the eukaryotic mitochondrion. We observed phenotypic similarity in S. cerevisiae genetic interaction data between mitochondrial ClpX (mtClpX) and genes contributing to heme biosynthesis, an essential mitochondrial function. Metabolomic analysis revealed that 5-aminolevulinic acid (ALA), the first heme precursor, is five-fold reduced in yeast lacking mtClpX activity, and total heme is reduced by half. mtClpX directly stimulates ALA synthase in vitro by catalyzing incorporation of its cofactor, pyridoxal phosphate. This activity is conserved in mammalian homologs; additionally, mtClpX depletion impairs vertebrate erythropoiesis, which requires massive upregulation of heme biosynthesis to supply hemoglobin. mtClpX therefore is a widely conserved stimulator of an essential biosynthetic pathway, and employs a previously unrecognized mechanism for AAA+ unfoldases. PMID:25957689

  5. KEY COMPARISON: BIPM comparison BIPM.RI(II)-K1.Rn-222 of activity measurements of the radionuclide 222Rn

    NASA Astrophysics Data System (ADS)

    Ratel, G.; Michotte, C.; Bochud, F. O.

    2004-01-01

    Since 2001, a national metrology institute, the Institut de Radiophysique Appliquée (IRA), Switzerland, has submitted two samples of known activity of 222Rn to the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures (BIPM). The activities ranged from about 13 kBq to 370 kBq. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by Section II of the Consultative Committee for Ionizing Radiation (CCRI(II)), with comparison identifier BIPM.RI(II)-K1.Rn-222, according to the provisions of the Mutual Recognition Arrangement (MRA).

  6. National Low-Level Waste Management Program final summary report of key activities and accomplishments for fiscal year 1997

    SciTech Connect

    Rittenberg, R.B.

    1998-03-01

    The US Department of Energy (DOE) has responsibilities under the Low-Level Radioactive Waste Policy Amendments Act of 1985 to assist states and compacts in their siting and licensing efforts for low-level radioactive waste disposal facilities. The National Low-Level Waste Management Program (NLLWMP) is the element of the DOE that performs the key support activities under the Act. The NLLWMP`s activities are driven by the needs of the states and compacts as they prepare to manage their low-level waste under the Act. Other work is added during the fiscal year as necessary to accommodate new requests brought on by status changes in states` and compacts` siting and licensing efforts. This report summarizes the activities and accomplishments of the NLLWMP during FY 1997.

  7. Active Region Oscillations: Results from SOHO JOP 097

    NASA Astrophysics Data System (ADS)

    O'Shea, E.; Fleck, B.; Muglach, K.; Sütterlin, P.

    2001-05-01

    We present here an analysis of data obtained in a sunspot region, using the Coronal Diagnostic Spectrometer (CDS) on SOHO. These data were obtained in the context of the Joint Observing Program (JOP) 97 which, together with CDS, included the Michelson Doppler Imaging (MDI) instrument on SOHO, the TRACE satellite and various ground based observatories, e.g. the DOT on La Palma. Using the lines of Fe XVI 335, Mg IX 368, He I 584, O III 599, Mg X 624 and O V 624 of CDS time series data were obtained in the pore and plage regions of sunspots associated with active regions AR 9166, 9166 and 9169 between September 19-29 2000. In addition to the time series datasets we also obtained 240 arcsec x 240 arcsec raster images of the sunspot regions examined. Using different time series analysis techniques we analyse the different periods of oscillation found in time series datasets and present the results here. This research is part of the European Solar Magnetometry Network supported by the EC through the TMR programme.

  8. ICARUS T600: physics results and future activities

    NASA Astrophysics Data System (ADS)

    Zani, Andrea

    2016-11-01

    The ICARUS T600 detector has proven the effectiveness of Liquid Argon TPC technology with a successful three-year long run at the INFN Gran Sasso National Laboratories (LNGS). ICARUS T600 LNGS data strongly contributed to the global effort in searching for neutrino oscillations mediated by sterile states. A definitive clarification of the sterile neutrino puzzle will come from the new multi-station, Short Baseline Neutrino (SBN) experiment at the Booster Neutrino Beam (BNB) at Fermilab, where a refurbished T600 will act as Far Detector. Presently the T600 detector is located at CERN, undergoing a major overhauling which will allow its participation in the 5 years program of the Fermilab upcoming SBN project. Moreover, ICARUS T600 is also foreseen to collect data with the NUMI Beam to be later exploited in the wider picture of the DUNE Long-Baseline project, recently undertaken by the United States community. This contribution will report the present physics results obtained by the ICARUS Collaboration, as well as describe the overhauling activities and the physics program for the detector in its future deployment at Fermilab.

  9. The flavonoid paradox: conjugation and deconjugation as key steps for the biological activity of flavonoids.

    PubMed

    Perez-Vizcaino, Francisco; Duarte, Juan; Santos-Buelga, Celestino

    2012-07-01

    Flavonoids have been proposed to exert beneficial effects in the prevention of a large number of diseases, including cancer, cardiovascular disease, and neurodegenerative disorders. Paradoxically, despite the most representative flavonoid--quercetin--exerting biologically demonstrable systemic effects, it is not found in plasma after oral administration and its circulating metabolites show weak activity in vitro. The current available evidence indicates that quercetin is extensively metabolized into methylated and glucurono- and sulfo-conjugated metabolites, which are the plasma circulating forms; and glucurono-, but not sulfo-conjugates, can be hydrolyzed at the vascular level, yielding the parent aglycone which accumulates in tissues. Thus conjugation is a reversible process and, at least regarding the vasodilator and antihypertensive effects, the conjugation-deconjugation cycle appears to be an absolute requirement. Glucuronidated derivatives transport quercetin and its methylated form, and deliver to the tissues the free aglycone, which is the final effector.

  10. Antibacterial activity of silver nanoparticles target sara through srna-teg49, a key mediator of hfq, in staphylococcus aureus

    PubMed Central

    Tian, Hu; Liao, Qiande; Liu, Meizhou; Hou, Jianhong; Zhang, Yangde; Liu, Ju

    2015-01-01

    Attributed to its antimicrobial effect, Silver nanoparticles (AgNPs) is widely used in various fields, such as biomedicine, textiles, health care products and food, etc. However, the antibacterial mechanism of AgNPs in staphylococcus aureus (S. aureus) by regulating sRNA expression remains largely unknown. Objectives: This study was performed to investigate the involvement of the antibacterial mechanism of AgNPs through sRNA-TEG49, a key mediator of Hfq, in S. aureus. Methods: Through the antimicrobial tests of AgNPs, its antibacterial laps and minimum inhibitory concentration was measured. A hierarchical cluster analysis of the differentially expressed sRNA in S. aureus was performed to investigate the relationship between AgNPs and sRNA. Expression of genes was analyzed by real-time PCR. Results: In the present study we found that at the concentrations higher than 1 mg/L, AgNPs could completely restrain bacteria growth, and the antibacterial activity of AgNPs apparently declined at the concentrations lower than 1 mg/L. S. aureus exposure to AgNPs, the expression of sRNA-TEG49, Hfq and sarA was significantly up-regulated in wild-type S. aureus. Moreover, Hfq loss-of-function inhibited the expression of sRNA-TEG49 in mutant-type S. aureus. Furthermore, sRNA-TEG49 loss-of-function associated with down-regulation the expression of sarA in mutant-type S. aureus. Conclusions: It was reasonable that Hfq regulated a distinct underlying molecular and antibacterial mechanism of AgNPs by forming a positive feedback loop with sRNA-TEG49. These observations suggested that Hfq plays an important role in the antibacterial mechanism of AgNPs by regulating sRNA-TEG49 expression, via its target sarA. PMID:26131167

  11. Is Active Management the Key to the Conservation of Saproxylic Biodiversity? Pollarding Promotes the Formation of Tree Hollows

    PubMed Central

    Sebek, Pavel; Altman, Jan; Platek, Michal; Cizek, Lukas

    2013-01-01

    Trees with hollows are key features sustaining biodiversity in wooded landscapes. They host rich assemblages of often highly specialised organisms. Hollow trees, however, have become rare and localised in Europe. Many of the associated biota is thus declining or endangered. The challenge of its conservation, therefore, is to safeguard the presence of hollow trees in sufficient numbers. Populations of numerous species associated with tree hollows and dead wood are often found in habitats that were formed by formerly common traditional silvicultural practices such as coppicing, pollarding or pasture. Although it has been occasionally mentioned that such practices increase the formation of hollows and the availability of often sun-exposed dead wood, their effect has never been quantified. Our study examined the hollow incidence in pollard and non-pollard (unmanaged) willows and the effect of pollarding on incremental growth rate by tree ring analysis. The probability of hollow occurrence was substantially higher in pollard than in non-pollard trees. Young pollards, especially, form hollows much more often than non-pollards; for instance, in trees of 50 cm DBH, the probability of hollow ocurrence was ∼0.75 in pollards, but only ∼0.3 in non-pollards. No difference in growth rate was found. Pollarding thus leads to the rapid formation of tree hollows, a habitat usually associated with old trees. It is therefore potentially a very important tool in the restoration of saproxylic habitats and conservation of hollow-dependent fauna. If applied along e.g. roads and watercourses, pollarding could also be used to increase landscape connectivity for saproxylic organisms. In reserves where pollarding was formerly practiced, its restoration would be necessary to prevent loss of saproxylic biodiversity. Our results point to the importance of active management measures for maintaining availability, and spatial and temporal continuity of deadwood microhabitats. PMID:23544142

  12. Representing Microbial Dormancy in Soil Decomposition Models Improves Model Performance and Reveals Key Ecosystem Controls on Microbial Activity

    NASA Astrophysics Data System (ADS)

    He, Y.; Yang, J.; Zhuang, Q.; Wang, G.; Liu, Y.

    2014-12-01

    Climate feedbacks from soils can result from environmental change and subsequent responses of plant and microbial communities and nutrient cycling. Explicit consideration of microbial life history traits and strategy may be necessary to predict climate feedbacks due to microbial physiology and community changes and their associated effect on carbon cycling. In this study, we developed an explicit microbial-enzyme decomposition model and examined model performance with and without representation of dormancy at six temperate forest sites with observed soil efflux ranged from 4 to 10 years across different forest types. We then extrapolated the model to all temperate forests in the Northern Hemisphere (25-50°N) to investigate spatial controls on microbial and soil C dynamics. Both models captured the observed soil heterotrophic respiration (RH), yet no-dormancy model consistently exhibited large seasonal amplitude and overestimation in microbial biomass. Spatially, the total RH from temperate forests based on dormancy model amounts to 6.88PgC/yr, and 7.99PgC/yr based on no-dormancy model. However, no-dormancy model notably overestimated the ratio of microbial biomass to SOC. Spatial correlation analysis revealed key controls of soil C:N ratio on the active proportion of microbial biomass, whereas local dormancy is primarily controlled by soil moisture and temperature, indicating scale-dependent environmental and biotic controls on microbial and SOC dynamics. These developments should provide essential support to modeling future soil carbon dynamics and enhance the avenue for collaboration between empirical soil experiment and modeling in the sense that more microbial physiological measurements are needed to better constrain and evaluate the models.

  13. Efficient production of optically pure L-lactic acid from food waste at ambient temperature by regulating key enzyme activity.

    PubMed

    Li, Xiang; Chen, Yinguang; Zhao, Shu; Chen, Hong; Zheng, Xiong; Luo, Jinyang; Liu, Yanan

    2015-03-01

    Bio-production of optically pure L-lactic acid from food waste has attracted much interest as it can treat organic wastes with simultaneous recovery of valuable by-products. However, the yield of L-lactic acid was very low and no optically pure L-lactic acid was produced in the literature due to (1) the lower activity of enzymes involved in hydrolysis and L-lactic acid generation, and (2) the participation of other enzymes related to D-lactic acid and acetic and propionic acids production. In this paper, a new strategy was reported for effective production of optically pure L-lactic acid from food waste at ambient temperature, i.e. via regulating key enzyme activity by sewage sludge supplement and intermittent alkaline fermentation. It was found that not only optically pure L-lactic acid was produced, but the yield was enhanced by 2.89-fold. The mechanism study showed that the activities of enzymes relevant to food waste hydrolysis and lactic acid production were enhanced, and the key enzymes related to volatile fatty acids and D-lactic acid generations were severally decreased or inhibited. Also, the microbes responsible for L-lactic acid production were selectively proliferated. Finally, the pilot-scale continuous experiment was conducted to testify the feasibility of this new technique.

  14. Assessment Results Following Inquiry and Traditional Physics Laboratory Activities

    ERIC Educational Resources Information Center

    Bryan, Joel Arthur

    2006-01-01

    Preservice elementary teachers in a conceptual physics course were given multiple resources to use during several inquiry activities in order to investigate how materials were chosen, used, and valued. These students performed significantly better on assessment items related to the inquiry physics activities than on items related to traditional…

  15. Key Role of Active-Site Water Molecules in Bacteriorhodopsin Proton-Transfer Reactions

    SciTech Connect

    Bondar, A.N.; Baudry, Jerome Y; Suhai, Sandor; Fischer, S.; Smith, Jeremy C

    2008-10-01

    The functional mechanism of the light-driven proton pump protein bacteriorhodopsin depends on the location of water molecules in the active site at various stages of the photocycle and on their roles in the proton-transfer steps. Here, free energy computations indicate that electrostatic interactions favor the presence of a cytoplasmic-side water molecule hydrogen bonding to the retinal Schiff base in the state preceding proton transfer from the retinal Schiff base to Asp85. However, the nonequilibrium nature of the pumping process means that the probability of occupancy of a water molecule in a given site depends both on the free energies of insertion of the water molecule in this and other sites during the preceding photocycle steps and on the kinetic accessibility of these sites on the time scale of the reaction steps. The presence of the cytoplasmic-side water molecule has a dramatic effect on the mechanism of proton transfer: the proton is channeled on the Thr89 side of the retinal, whereas the transfer on the Asp212 side is hindered. Reaction-path simulations and molecular dynamics simulations indicate that the presence of the cytoplasmic-side water molecule permits a low-energy bacteriorhodopsin conformer in which the water molecule bridges the twisted retinal Schiff base and the proton acceptor Asp85. From this low-energy conformer, proton transfer occurs via a concerted mechanism in which the water molecule participates as an intermediate proton carrier.

  16. A Detailed Data-Driven Network Model of Prefrontal Cortex Reproduces Key Features of In Vivo Activity

    PubMed Central

    Hass, Joachim; Hertäg, Loreen; Durstewitz, Daniel

    2016-01-01

    The prefrontal cortex is centrally involved in a wide range of cognitive functions and their impairment in psychiatric disorders. Yet, the computational principles that govern the dynamics of prefrontal neural networks, and link their physiological, biochemical and anatomical properties to cognitive functions, are not well understood. Computational models can help to bridge the gap between these different levels of description, provided they are sufficiently constrained by experimental data and capable of predicting key properties of the intact cortex. Here, we present a detailed network model of the prefrontal cortex, based on a simple computationally efficient single neuron model (simpAdEx), with all parameters derived from in vitro electrophysiological and anatomical data. Without additional tuning, this model could be shown to quantitatively reproduce a wide range of measures from in vivo electrophysiological recordings, to a degree where simulated and experimentally observed activities were statistically indistinguishable. These measures include spike train statistics, membrane potential fluctuations, local field potentials, and the transmission of transient stimulus information across layers. We further demonstrate that model predictions are robust against moderate changes in key parameters, and that synaptic heterogeneity is a crucial ingredient to the quantitative reproduction of in vivo-like electrophysiological behavior. Thus, we have produced a physiologically highly valid, in a quantitative sense, yet computationally efficient PFC network model, which helped to identify key properties underlying spike time dynamics as observed in vivo, and can be harvested for in-depth investigation of the links between physiology and cognition. PMID:27203563

  17. A Detailed Data-Driven Network Model of Prefrontal Cortex Reproduces Key Features of In Vivo Activity.

    PubMed

    Hass, Joachim; Hertäg, Loreen; Durstewitz, Daniel

    2016-05-01

    The prefrontal cortex is centrally involved in a wide range of cognitive functions and their impairment in psychiatric disorders. Yet, the computational principles that govern the dynamics of prefrontal neural networks, and link their physiological, biochemical and anatomical properties to cognitive functions, are not well understood. Computational models can help to bridge the gap between these different levels of description, provided they are sufficiently constrained by experimental data and capable of predicting key properties of the intact cortex. Here, we present a detailed network model of the prefrontal cortex, based on a simple computationally efficient single neuron model (simpAdEx), with all parameters derived from in vitro electrophysiological and anatomical data. Without additional tuning, this model could be shown to quantitatively reproduce a wide range of measures from in vivo electrophysiological recordings, to a degree where simulated and experimentally observed activities were statistically indistinguishable. These measures include spike train statistics, membrane potential fluctuations, local field potentials, and the transmission of transient stimulus information across layers. We further demonstrate that model predictions are robust against moderate changes in key parameters, and that synaptic heterogeneity is a crucial ingredient to the quantitative reproduction of in vivo-like electrophysiological behavior. Thus, we have produced a physiologically highly valid, in a quantitative sense, yet computationally efficient PFC network model, which helped to identify key properties underlying spike time dynamics as observed in vivo, and can be harvested for in-depth investigation of the links between physiology and cognition.

  18. Strong Nonadditivity as a Key Structure–Activity Relationship Feature: Distinguishing Structural Changes from Assay Artifacts

    PubMed Central

    2015-01-01

    Nonadditivity in protein–ligand affinity data represents highly instructive structure–activity relationship (SAR) features that indicate structural changes and have the potential to guide rational drug design. At the same time, nonadditivity is a challenge for both basic SAR analysis as well as many ligand-based data analysis techniques such as Free-Wilson Analysis and Matched Molecular Pair analysis, since linear substituent contribution models inherently assume additivity and thus do not work in such cases. While structural causes for nonadditivity have been analyzed anecdotally, no systematic approaches to interpret and use nonadditivity prospectively have been developed yet. In this contribution, we lay the statistical framework for systematic analysis of nonadditivity in a SAR series. First, we develop a general metric to quantify nonadditivity. Then, we demonstrate the non-negligible impact of experimental uncertainty that creates apparent nonadditivity, and we introduce techniques to handle experimental uncertainty. Finally, we analyze public SAR data sets for strong nonadditivity and use recourse to the original publications and available X-ray structures to find structural explanations for the nonadditivity observed. We find that all cases of strong nonadditivity (ΔΔpKi and ΔΔpIC50 > 2.0 log units) with sufficient structural information to generate reasonable hypothesis involve changes in binding mode. With the appropriate statistical basis, nonadditivity analysis offers a variety of new attempts for various areas in computer-aided drug design, including the validation of scoring functions and free energy perturbation approaches, binding pocket classification, and novel features in SAR analysis tools. PMID:25760829

  19. A historical analysis of Plinian unrest and the key promoters of explosive activity.

    NASA Astrophysics Data System (ADS)

    Winson, A. E. G.; Newhall, C. G.; Costa, F.

    2015-12-01

    Plinian eruptions are the largest historically recorded volcanic phenomena, and have the potential to be widely destructive. Yet when a volcano becomes newly restless we are unable to anticipate whether or not a large eruption is imminent. We present the findings from a multi-parametric study of 42 large explosive eruptions (29 Plinian and 13 Sub-plinian) that form the basis for a new Bayesian Belief network that addresses this question. We combine the eruptive history of the volcanoes that have produced these large eruptions with petrological studies, and reported unrest phenomena to assess the probability of an eruption being plinian. We find that the 'plinian probability' is increased most strongly by the presence of an exsolved volatile phase in the reservoir prior to an eruption. In our survey 60% of the plinian eruptions, had an excess SO2 gas phase of more than double than it is calculated by petrologic studies alone. Probability is also increased by three related and more easily observable parameters: a high plinian Ratio (that is the ratio of VEI≥4 eruptions in a volcanoes history to the number of all VEI≥2 eruptions in the history), a repose time of more than 1000 years, and a Repose Ratio (the ratio of the average return of VEI≥4 eruptions in the volcanic record to the repose time since the last VEI≥4) of greater than 0.7. We looked for unrest signals that potentially are indicative of future plinian activity and report a few observations from case studies but cannot say if these will generally appear. Finally we present a retrospective analysis of the probabilities of eruptions in our study becoming plinian, using our Bayesian belief network. We find that these probabilities are up to about 4 times greater than those calculate from an a priori assessment of the global eruptive catalogue.

  20. Addressing key concepts in physical geography through interactive learning activities in an online geo-ICT environment

    NASA Astrophysics Data System (ADS)

    Verstraeten, Gert; Steegen, An; Martens, Lotte

    2016-04-01

    The increasing number of geospatial datasets and free online geo-ICT tools offers new opportunities for education in Earth Sciences. Geospatial technology indeed provides an environment through which interactive learning can be introduced in Earth Sciences curricula. However, the effectiveness of such e-learning approaches in terms of learning outcomes has rarely been addressed. Here, we present our experience with the implementation of digital interactive learning activities within an introductory Physical Geography course attended by 90 undergraduate students in Geography, Geology, Biology and Archaeology. Two traditional lectures were replaced by interactive sessions (each 2 h) in a flexible classroom where students had to work both in team and individually in order to explore some key concepts through the integrated use of geospatial data within Google EarthTM. A first interactive lesson dealt with the classification of river systems and aimed to examine the conditions under which rivers tend to meander or to develop a braided pattern. Students were required to collect properties of rivers (river channel pattern, channel slope, climate, discharge, lithology, vegetation, etc). All these data are available on a global scale and have been added as separate map layers in Google EarthTM. Each student collected data for at least two rivers and added this information to a Google Drive Spreadsheet accessible to the entire group. This resulted in a database of more than one hundred rivers spread over various environments worldwide. In a second phase small groups of students discussed the potential relationships between river channel pattern and its controlling factors. Afterwards, the findings of each discussion group were presented to the entire audience. The same set-up was followed in a second interactive session to explore spatial variations in ecosystem properties such as net primary production and soil carbon content. The qualitative evaluation of both interactive

  1. Mitochondrial Activity and Cyr1 Are Key Regulators of Ras1 Activation of C. albicans Virulence Pathways

    PubMed Central

    Grahl, Nora; Demers, Elora G.; Lindsay, Allia K.; Harty, Colleen E.; Willger, Sven D.; Piispanen, Amy E.; Hogan, Deborah A.

    2015-01-01

    Candida albicans is both a major fungal pathogen and a member of the commensal human microflora. The morphological switch from yeast to hyphal growth is associated with disease and many environmental factors are known to influence the yeast-to-hyphae switch. The Ras1-Cyr1-PKA pathway is a major regulator of C. albicans morphogenesis as well as biofilm formation and white-opaque switching. Previous studies have shown that hyphal growth is strongly repressed by mitochondrial inhibitors. Here, we show that mitochondrial inhibitors strongly decreased Ras1 GTP-binding and activity in C. albicans and similar effects were observed in other Candida species. Consistent with there being a connection between respiratory activity and GTP-Ras1 binding, mutants lacking complex I or complex IV grew as yeast in hypha-inducing conditions, had lower levels of GTP-Ras1, and Ras1 GTP-binding was unaffected by respiratory inhibitors. Mitochondria-perturbing agents decreased intracellular ATP concentrations and metabolomics analyses of cells grown with different respiratory inhibitors found consistent perturbation of pyruvate metabolism and the TCA cycle, changes in redox state, increased catabolism of lipids, and decreased sterol content which suggested increased AMP kinase activity. Biochemical and genetic experiments provide strong evidence for a model in which the activation of Ras1 is controlled by ATP levels in an AMP kinase independent manner. The Ras1 GTPase activating protein, Ira2, but not the Ras1 guanine nucleotide exchange factor, Cdc25, was required for the reduction of Ras1-GTP in response to inhibitor-mediated reduction of ATP levels. Furthermore, Cyr1, a well-characterized Ras1 effector, participated in the control of Ras1-GTP binding in response to decreased mitochondrial activity suggesting a revised model for Ras1 and Cyr1 signaling in which Cyr1 and Ras1 influence each other and, together with Ira2, seem to form a master-regulatory complex necessary to integrate

  2. Where’s the Noise? Key Features of Spontaneous Activity and Neural Variability Arise through Learning in a Deterministic Network

    PubMed Central

    Hartmann, Christoph; Lazar, Andreea; Nessler, Bernhard; Triesch, Jochen

    2015-01-01

    Even in the absence of sensory stimulation the brain is spontaneously active. This background “noise” seems to be the dominant cause of the notoriously high trial-to-trial variability of neural recordings. Recent experimental observations have extended our knowledge of trial-to-trial variability and spontaneous activity in several directions: 1. Trial-to-trial variability systematically decreases following the onset of a sensory stimulus or the start of a motor act. 2. Spontaneous activity states in sensory cortex outline the region of evoked sensory responses. 3. Across development, spontaneous activity aligns itself with typical evoked activity patterns. 4. The spontaneous brain activity prior to the presentation of an ambiguous stimulus predicts how the stimulus will be interpreted. At present it is unclear how these observations relate to each other and how they arise in cortical circuits. Here we demonstrate that all of these phenomena can be accounted for by a deterministic self-organizing recurrent neural network model (SORN), which learns a predictive model of its sensory environment. The SORN comprises recurrently coupled populations of excitatory and inhibitory threshold units and learns via a combination of spike-timing dependent plasticity (STDP) and homeostatic plasticity mechanisms. Similar to balanced network architectures, units in the network show irregular activity and variable responses to inputs. Additionally, however, the SORN exhibits sequence learning abilities matching recent findings from visual cortex and the network’s spontaneous activity reproduces the experimental findings mentioned above. Intriguingly, the network’s behaviour is reminiscent of sampling-based probabilistic inference, suggesting that correlates of sampling-based inference can develop from the interaction of STDP and homeostasis in deterministic networks. We conclude that key observations on spontaneous brain activity and the variability of neural responses can be

  3. Stellar activity and coronal heating: an overview of recent results

    PubMed Central

    Testa, Paola; Saar, Steven H.; Drake, Jeremy J.

    2015-01-01

    Observations of the coronae of the Sun and of solar-like stars provide complementary information to advance our understanding of stellar magnetic activity, and of the processes leading to the heating of their outer atmospheres. While solar observations allow us to study the corona at high spatial and temporal resolution, the study of stellar coronae allows us to probe stellar activity over a wide range of ages and stellar parameters. Stellar studies therefore provide us with additional tools for understanding coronal heating processes, as well as the long-term evolution of solar X-ray activity. We discuss how recent studies of stellar magnetic fields and coronae contribute to our understanding of the phenomenon of activity and coronal heating in late-type stars. PMID:25897087

  4. Stellar activity and coronal heating: an overview of recent results.

    PubMed

    Testa, Paola; Saar, Steven H; Drake, Jeremy J

    2015-05-28

    Observations of the coronae of the Sun and of solar-like stars provide complementary information to advance our understanding of stellar magnetic activity, and of the processes leading to the heating of their outer atmospheres. While solar observations allow us to study the corona at high spatial and temporal resolution, the study of stellar coronae allows us to probe stellar activity over a wide range of ages and stellar parameters. Stellar studies therefore provide us with additional tools for understanding coronal heating processes, as well as the long-term evolution of solar X-ray activity. We discuss how recent studies of stellar magnetic fields and coronae contribute to our understanding of the phenomenon of activity and coronal heating in late-type stars.

  5. (Un-)expected nocturnal activity in "Diurnal" Lemur catta supports cathemerality as one of the key adaptations of the lemurid radiation.

    PubMed

    Donati, Giuseppe; Santini, Luca; Razafindramanana, Josia; Boitani, Luigi; Borgognini-Tarli, Silvana

    2013-01-01

    The ability to operate during the day and at night (i.e., cathemerality) is common among mammals but has rarely been identified in primates. Adaptive hypotheses assume that cathemerality represents a stable adaptation in primates, while nonadaptive hypotheses propose that it is the result of an evolutionary disequilibrium arising from human impacts on natural habitats. Madagascar offers a unique opportunity to study the evolution of activity patterns as there we find a monophyletic primate radiation that shows nocturnal, diurnal, and cathemeral patterns. However, when and why cathemeral activity evolved in lemurs is the subject of intense debate. Thus far, this activity pattern has been regularly observed in only three lemurid genera but the actual number of lemur species exhibiting this activity is as yet unknown. Here we show that the ring-tailed lemur, Lemur catta, a species previously considered to be diurnal, can in fact be cathemeral in the wild. In neighboring but distinct forest areas these lemurs exhibited either mainly diurnal or cathemeral activity. We found that, as in other cathemeral lemurs, activity was entrained by photoperiod and masked by nocturnal luminosity. Our results confirm the relationship between transitional eye anatomy and physiology and 24-h activity, thus supporting the adaptive scenario. Also, on the basis of the most recent strepsirrhine phylogenetic reconstruction, using parsimony criterion, our findings suggest pushing back the emergence of cathemerality to stem lemurids. Flexible activity over 24-h could thus have been one of the key adaptations of the early lemurid radiation possibly driven by Madagascar's island ecology.

  6. Charpy impact test results for low-activation ferritic alloys

    SciTech Connect

    Cannon, N.S.; Hu, W.L.; Gelles, D.S.

    1987-05-01

    The objective of this work is to evaluate the shift of the ductile to brittle transition temperature (DBTT) and the reduction of the upper shelf energy (USE) due to neutron irradiation of low activation ferritic alloys. Six low activation ferritic alloys have been tested following irradiation at 365/sup 0/C to 10 dpa and compared with control specimens in order to assess the effect of irradiation on Charpy impact properties.

  7. Tc-99 Adsorption on Selected Activated Carbons - Batch Testing Results

    SciTech Connect

    Mattigod, Shas V.; Wellman, Dawn M.; Golovich, Elizabeth C.; Cordova, Elsa A.; Smith, Ronald M.

    2010-12-01

    CH2M HILL Plateau Remediation Company (CHPRC) is currently developing a 200-West Area groundwater pump-and-treat system as the remedial action selected under the Comprehensive Environmental Response, Compensation, and Liability Act Record of Decision for Operable Unit (OU) 200-ZP-1. This report documents the results of treatability tests Pacific Northwest National Laboratory researchers conducted to quantify the ability of selected activated carbon products (or carbons) to adsorb technetium-99 (Tc-99) from 200-West Area groundwater. The Tc-99 adsorption performance of seven activated carbons (J177601 Calgon Fitrasorb 400, J177606 Siemens AC1230AWC, J177609 Carbon Resources CR-1240-AW, J177611 General Carbon GC20X50, J177612 Norit GAC830, J177613 Norit GAC830, and J177617 Nucon LW1230) were evaluated using water from well 299-W19-36. Four of the best performing carbons (J177606 Siemens AC1230AWC, J177609 Carbon Resources CR-1240-AW, J177611 General Carbon GC20X50, and J177613 Norit GAC830) were selected for batch isotherm testing. The batch isotherm tests on four of the selected carbons indicated that under lower nitrate concentration conditions (382 mg/L), Kd values ranged from 6,000 to 20,000 mL/g. In comparison. Under higher nitrate (750 mg/L) conditions, there was a measureable decrease in Tc-99 adsorption with Kd values ranging from 3,000 to 7,000 mL/g. The adsorption data fit both the Langmuir and the Freundlich equations. Supplemental tests were conducted using the two carbons that demonstrated the highest adsorption capacity to resolve the issue of the best fit isotherm. These tests indicated that Langmuir isotherms provided the best fit for Tc-99 adsorption under low nitrate concentration conditions. At the design basis concentration of Tc 0.865 µg/L(14,700 pCi/L), the predicted Kd values from using Langmuir isotherm constants were 5,980 mL/g and 6,870 mL/g for for the two carbons. These Kd values did not meet the target Kd value of 9,000 mL/g. Tests

  8. Benchmarking Evaluation Results for Prototype Extravehicular Activity Gloves

    NASA Technical Reports Server (NTRS)

    Aitchison, Lindsay; McFarland, Shane

    2012-01-01

    The Space Suit Assembly (SSA) Development Team at NASA Johnson Space Center has invested heavily in the advancement of rear-entry planetary exploration suit design but largely deferred development of extravehicular activity (EVA) glove designs, and accepted the risk of using the current flight gloves, Phase VI, for unique mission scenarios outside the Space Shuttle and International Space Station (ISS) Program realm of experience. However, as design reference missions mature, the risks of using heritage hardware have highlighted the need for developing robust new glove technologies. To address the technology gap, the NASA Game-Changing Technology group provided start-up funding for the High Performance EVA Glove (HPEG) Project in the spring of 2012. The overarching goal of the HPEG Project is to develop a robust glove design that increases human performance during EVA and creates pathway for future implementation of emergent technologies, with specific aims of increasing pressurized mobility to 60% of barehanded capability, increasing the durability by 100%, and decreasing the potential of gloves to cause injury during use. The HPEG Project focused initial efforts on identifying potential new technologies and benchmarking the performance of current state of the art gloves to identify trends in design and fit leading to establish standards and metrics against which emerging technologies can be assessed at both the component and assembly levels. The first of the benchmarking tests evaluated the quantitative mobility performance and subjective fit of four prototype gloves developed by Flagsuit LLC, Final Frontier Designs, LLC Dover, and David Clark Company as compared to the Phase VI. All of the companies were asked to design and fabricate gloves to the same set of NASA provided hand measurements (which corresponded to a single size of Phase Vi glove) and focus their efforts on improving mobility in the metacarpal phalangeal and carpometacarpal joints. Four test

  9. Identification of key residues in virulent canine distemper virus hemagglutinin that control CD150/SLAM-binding activity.

    PubMed

    Zipperle, Ljerka; Langedijk, Johannes P M; Orvell, Claes; Vandevelde, Marc; Zurbriggen, Andreas; Plattet, Philippe

    2010-09-01

    Morbillivirus cell entry is controlled by hemagglutinin (H), an envelope-anchored viral glycoprotein determining interaction with multiple host cell surface receptors. Subsequent to virus-receptor attachment, H is thought to transduce a signal triggering the viral fusion glycoprotein, which in turn drives virus-cell fusion activity. Cell entry through the universal morbillivirus receptor CD150/SLAM was reported to depend on two nearby microdomains located within the hemagglutinin. Here, we provide evidence that three key residues in the virulent canine distemper virus A75/17 H protein (Y525, D526, and R529), clustering at the rim of a large recessed groove created by beta-propeller blades 4 and 5, control SLAM-binding activity without drastically modulating protein surface expression or SLAM-independent F triggering.

  10. Key Immune Cell Cytokines Affects the Telomere Activity of Cord Blood Cells In vitro

    PubMed Central

    Brazvan, Balal; Farahzadi, Raheleh; Mohammadi, Seyede Momeneh; Montazer Saheb, Soheila; Shanehbandi, Dariush; Schmied, Laurent; Soleimani Rad, Jafar; Darabi, Masoud; Nozad Charoudeh, Hojjatollah

    2016-01-01

    Purpose: Telomere is a nucleoprotein complex at the end of eukaryotic chromosomes and its length is regulated by telomerase. The number of DNA repeat sequence (TTAGGG)n is reduced with each cell division in differentiated cells. The aim of this study was to evaluate the effect of SCF (Stem Cell Factor), Flt3 (Fms- Like tyrosine kinase-3), Interleukin-2, 7 and 15 on telomere length and hTERT gene expression in mononuclear and umbilical cord blood stem cells (CD34+ cells) during development to lymphoid cells. Methods: The mononuclear cells were isolated from umbilical cord blood by Ficoll-Paque density gradient. Then cells were cultured for 21 days in the presence of different cytokines. Telomere length and hTERT gene expression were evaluated in freshly isolated cells, 7, 14 and 21 days of culture by real-time PCR. The same condition had been done for CD34+ cells but telomere length and hTERT gene expression were measured at initial and day 21 of the experiment. Results: Highest hTERT gene expression and maximum telomere length were measured at day14 of MNCs in the presence of IL-7 and IL-15. Also, there was a significant correlation between telomere length and telomerase gene expression in MNCs at 14 days in a combination of IL-7 and IL-15 (r = 0.998, p =0.04). In contrast, IL-2 showed no distinct effect on telomere length and hTERT gene expression in cells. Conclusion: Taken together, IL-7 and IL-15 increased telomere length and hTERT gene expression at 14 day of the experiment. In conclusion, it seems likely that cells maintain naïve phenotype due to prolonged exposure of IL-7 and IL-15. PMID:27478776

  11. Silencing of Doublecortin-Like (DCL) Results in Decreased Mitochondrial Activity and Delayed Neuroblastoma Tumor Growth

    PubMed Central

    Verissimo, Carla S.; Elands, Rachel; Cheng, Sou; Saaltink, Dirk-Jan; ter Horst, Judith P.; Alme, Maria N.; Pont, Chantal; van de Water, Bob; Håvik, Bjarte; Fitzsimons, Carlos P.; Vreugdenhil, Erno

    2013-01-01

    Doublecortin-like (DCL) is a microtubule-binding protein crucial for neuroblastoma (NB) cell proliferation. We have investigated whether the anti-proliferative effect of DCL knockdown is linked to reduced mitochondrial activity. We found a delay in tumor development after DCL knockdown in vivo in doxycycline-inducible NB tumor xenografts. To understand the mechanisms underlying this tumor growth retardation we performed a series of in vitro experiments in NB cell lines. DCL colocalizes with mitochondria, interacts with the mitochondrial outer membrane protein OMP25/ SYNJ2BP and DCL knockdown results in decreased expression of genes involved in oxidative phosphorylation. Moreover, DCL knockdown decreases cytochrome c oxidase activity and ATP synthesis. We identified the C-terminal Serine/Proline-rich domain and the second microtubule-binding area as crucial DCL domains for the regulation of cytochrome c oxidase activity and ATP synthesis. Furthermore, DCL knockdown causes a significant reduction in the proliferation rate of NB cells under an energetic challenge induced by low glucose availability. Together with our previous studies, our results corroborate DCL as a key player in NB tumor growth in which DCL controls not only mitotic spindle formation and the stabilization of the microtubule cytoskeleton, but also regulates mitochondrial activity and energy availability, which makes DCL a promising molecular target for NB therapy. PMID:24086625

  12. Annoyance resulting from intrusion of aircraft sounds upon various activities

    NASA Technical Reports Server (NTRS)

    Gunn, W. J.; Shepherd, W. T.; Fletcher, J. L.

    1975-01-01

    An experiment was conducted in which subjects were engaged in TV viewing, telephone listening, or reverie (no activity) for a 1/2-hour session. During the session, they were exposed to a series of recorded aircraft sounds at the rate of one flight every 2 minutes. Within each session, four levels of flyover noise, separated by dB increments, were presented several times in a Latin Square balanced sequence. The peak level of the noisiest flyover in any session was fixed at 95, 90, 85, 75, or 70 dBA. At the end of the test session, subjects recorded their responses to the aircraft sounds, using a bipolar scale which covered the range from very pleasant to extremely annoying. Responses to aircraft noises were found to be significantly affected by the particular activity in which the subjects were engaged. Not all subjects found the aircraft sounds to be annoying.

  13. Citric-acid cycle key enzyme activities during in vitro growth and metacyclogenesis of Leishmania infantum promastigotes.

    PubMed

    Louassini, M; Foulquié, M; Benítez, R; Adroher, J

    1999-08-01

    The activities of 5 key regulatory enzymes in most energetic systems, namely citrate synthase (EC 4.1.3.7, CS), NADP-specific isocitrate dehydrogenase (EC 1.1.1.42, ICDH), succinate dehydrogenase (EC 1.3.99.1, SDH), L-malate dehydrogenase (EC 1.1.1.37, MDH), and decarboxylating malic enzyme (EC 1.1.1.40, ME), were measured during the growth and metacyclogenesis of a cutaneous (CL) and a visceral (VL) strain of Leishmania infantum. As occurs with other Leishmania species, infective promastigotes were present along all phases of growth, but their percentages were higher at the early stationary phase for VL and the end of the same phase for CL. High CS and SDH activities were detected in both strains, as compared with other trypanosomatids, bringing more evidence for an actively functional citric-acid cycle in L. infantum. Both strains showed higher levels of CS, ICDH, and MDH and lower SDH and ME activities when more metacyclic promastigotes were present, but in VL these changes paralleled an increase in glucose consumption, whereas in CL these changes coincided with an NH3 hyperproduction. This suggests that the energy metabolism during L. infantum growth and metacyclogenesis is affected by regulated enzymes that probably respond to changes in the culture medium in the levels of glucose and amino acids.

  14. NLRP3 inflammasome activation by mitochondrial reactive oxygen species plays a key role in long-term cognitive impairment induced by paraquat exposure.

    PubMed

    Chen, Liuji; Na, Ren; Boldt, Erin; Ran, Qitao

    2015-09-01

    Exposure to environmental toxins such as pesticides is implicated in increasing Alzheimer's disease risk. In this study, we investigated the long-term effects of paraquat exposure on cognition of Alzheimer's disease animal model APP/PS1 mice and wild-type (WT) mice. Our results showed that APP/PS1 mice had exacerbated cognition impairment and elevated Aβ levels at 5 months after paraquat exposure, and that WT mice had cognition impairment at 5 and 16 months after paraquat exposure. In addition, increased mitochondrial oxidative stress and augmented brain inflammation were observed in both paraquat-exposed APP/PS1 mice and WT mice. Interestingly, activation of NLRP3 inflammasome, which triggers inflammation in response to mitochondrial stress, was enhanced in paraquat-exposed mice. Moreover, transgenic mice overexpressing Prdx3, a key enzyme in detoxifying mitochondrial H2O2, had suppressed NLRP3 inflammasome activation, reduced brain inflammation, and attenuated cognition impairment after paraquat exposure. Together, our results indicate that NLRP3 inflammasome activation induced by mitochondrial reactive oxygen species plays a key role in mediating paraquat-induced long-term cognition decline by elevating brain inflammation.

  15. A mental health needs assessment of children and adolescents in post-conflict Liberia: results from a quantitative key-informant survey

    PubMed Central

    Borba, Christina P.C.; Ng, Lauren C.; Stevenson, Anne; Vesga-Lopez, Oriana; Harris, Benjamin L.; Parnarouskis, Lindsey; Gray, Deborah A.; Carney, Julia R.; Domínguez, Silvia; Wang, Edward K.S.; Boxill, Ryan; Song, Suzan J.; Henderson, David C.

    2016-01-01

    Between 1989 and 2004, Liberia experienced a devastating civil war that resulted in widespread trauma with almost no mental health infrastructure to help citizens cope. In 2009, the Liberian Ministry of Health and Social Welfare collaborated with researchers from Massachusetts General Hospital to conduct a rapid needs assessment survey in Liberia with local key informants (n = 171) to examine the impact of war and post-war events on emotional and behavioral problems of, functional limitations of, and appropriate treatment settings for Liberian youth aged 5–22. War exposure and post-conflict sexual violence, poverty, infectious disease and parental death negatively impacted youth mental health. Key informants perceived that youth displayed internalizing and externalizing symptoms and mental health-related functional impairment at home, school, work and in relationships. Medical clinics were identified as the most appropriate setting for mental health services. Youth in Liberia continue to endure the harsh social, economic and material conditions of everyday life in a protracted post-conflict state, and have significant mental health needs. Their observed functional impairment due to mental health issues further limited their access to protective factors such as education, employment and positive social relationships. Results from this study informed Liberia's first post-conflict mental health policy. PMID:26807147

  16. A mental health needs assessment of children and adolescents in post-conflict Liberia: results from a quantitative key-informant survey.

    PubMed

    Borba, Christina P C; Ng, Lauren C; Stevenson, Anne; Vesga-Lopez, Oriana; Harris, Benjamin L; Parnarouskis, Lindsey; Gray, Deborah A; Carney, Julia R; Domínguez, Silvia; Wang, Edward K S; Boxill, Ryan; Song, Suzan J; Henderson, David C

    2016-01-02

    Between 1989 and 2004, Liberia experienced a devastating civil war that resulted in widespread trauma with almost no mental health infrastructure to help citizens cope. In 2009, the Liberian Ministry of Health and Social Welfare collaborated with researchers from Massachusetts General Hospital to conduct a rapid needs assessment survey in Liberia with local key informants (n = 171) to examine the impact of war and post-war events on emotional and behavioral problems of, functional limitations of, and appropriate treatment settings for Liberian youth aged 5-22. War exposure and post-conflict sexual violence, poverty, infectious disease and parental death negatively impacted youth mental health. Key informants perceived that youth displayed internalizing and externalizing symptoms and mental health-related functional impairment at home, school, work and in relationships. Medical clinics were identified as the most appropriate setting for mental health services. Youth in Liberia continue to endure the harsh social, economic and material conditions of everyday life in a protracted post-conflict state, and have significant mental health needs. Their observed functional impairment due to mental health issues further limited their access to protective factors such as education, employment and positive social relationships. Results from this study informed Liberia's first post-conflict mental health policy.

  17. Experimental results using active control of traveling wave power flow

    NASA Technical Reports Server (NTRS)

    Miller, David W.; Hall, Steven R.

    1991-01-01

    Active structural control experiments conducted on a 24-ft pinned-free beam derived feedback compensators on the basis of a traveling-wave approach. A compensator is thus obtained which eliminates resonant behavior by absorbing all impinging power. A causal solution is derived for this noncausal compensator which mimics its behavior in a given frequency range, using the Wiener-Hopf. This optimal Wiener-Hopf compensator's structure-damping performance is found to exceed any obtainable by means of rate feedback. Performance limitations encompassed the discovery of frequencies above which the sensor and actuator were no longer dual and an inadvertent coupling of the control hardware to unmodeled structure torsion modes.

  18. Towards active capsular endoscopy: preliminary results on a legged platform.

    PubMed

    Menciassi, Arianna; Stefanini, Cesare; Orlandi, Giovanni; Quirini, Marco; Dario, Paolo

    2006-01-01

    This paper illustrates the problem of active locomotion in the gastrointestinal tract for endoscopic capsules. Authors analyze the problem of locomotion in unstructured, flexible and tubular environments and explain the reasons leading to the selection of a legged system. They present a theoretical simulation of legged capsule locomotion, which is used to define the optimal parameters for capsule design and gait selection. Finally, a legged capsule--about 3 cm3 in volume--is presented; it consists of 4 back legs whose actuation is achieved thanks to a miniaturized DC brushless motor. In vitro tests demonstrate good performance in terms of achievable speed (92 mm/min).

  19. The SEDIBUD (Sediment Budgets in Cold Environments) Programme: Ongoing activities and selected key tasks for the coming years

    NASA Astrophysics Data System (ADS)

    Beylich, Achim A.; Lamoureux, Scott F.; Decaulne, Armelle

    2012-09-01

    Projected climate change in cold environments is expected to alter melt-season duration and intensity, along with the number of extreme rainfall events, total annual precipitation and the balance between snowfall and rainfall. In addition, changes to the thermal balance are expected to reduce the extent of permafrost and seasonal ground frost and increase active layer depths. The combined effects of these changes will alter surface environments in cold climate regions and change the fluxes of sediments, nutrients and solutes, but the absence of data, coordinated process monitoring and coordinated quantitative analysis to understand the sensitivity of the Earth surface environment are acute in cold climate environments. The International Association of Geomorphologists (I.A.G./A.I.G.) SEDIBUD (Sediment Budgets in Cold Environments) Programme has been formed to address this key knowledge gap and builds on the earlier European Science Foundation (ESF) SEDIFLUX (Sedimentary Source-to-Sink-Fluxes in Cold Environments) Network. Coordinated efforts are carried out to monitor, quantify, compare and model sedimentary fluxes and possible effects of predicted climate change in currently 44 selected SEDIBUD Key Test Sites (cold climate environment catchments) worldwide.

  20. Hellenic Amateur Astronomy Association's activities: Preliminary results on Perseids 2010

    NASA Astrophysics Data System (ADS)

    Maravelias, G.

    2011-01-01

    Preliminary results on the Perseids 2010 are presented. Visual and video observations were obtained by the author and a first reduction of the visual data shows that a maximum of ZHR ~120 was reached during the night 12-13 of August 2010. Moreover, a video setup was tested (DMK camera and UFO Capture v2) and the results show that, under some limitations, valuable data can be obtained.

  1. Probing the catalytic mechanism of bovine CD38/NAD+ glycohydrolase by site directed mutagenesis of key active site residues.

    PubMed

    Kuhn, Isabelle; Kellenberger, Esther; Cakir-Kiefer, Céline; Muller-Steffner, Hélène; Schuber, Francis

    2014-07-01

    Bovine CD38/NAD(+) glycohydrolase catalyzes the hydrolysis of NAD(+) to nicotinamide and ADP-ribose and the formation of cyclic ADP-ribose via a stepwise reaction mechanism. Our recent crystallographic study of its Michaelis complex and covalently-trapped intermediates provided insights into the modalities of substrate binding and the molecular mechanism of bCD38. The aim of the present work was to determine the precise role of key conserved active site residues (Trp118, Glu138, Asp147, Trp181 and Glu218) by focusing mainly on the cleavage of the nicotinamide-ribosyl bond. We analyzed the kinetic parameters of mutants of these residues which reside within the bCD38 subdomain in the vicinity of the scissile bond of bound NAD(+). To address the reaction mechanism we also performed chemical rescue experiments with neutral (methanol) and ionic (azide, formate) nucleophiles. The crucial role of Glu218, which orients the substrate for cleavage by interacting with the N-ribosyl 2'-OH group of NAD(+), was highlighted. This contribution to catalysis accounts for almost half of the reaction energy barrier. Other contributions can be ascribed notably to Glu138 and Asp147 via ground-state destabilization and desolvation in the vicinity of the scissile bond. Key interactions with Trp118 and Trp181 were also proven to stabilize the ribooxocarbenium ion-like transition state. Altogether we propose that, as an alternative to a covalent acylal reaction intermediate with Glu218, catalysis by bCD38 proceeds through the formation of a discrete and transient ribooxocarbenium intermediate which is stabilized within the active site mostly by electrostatic interactions.

  2. Summary of FY15 results of benchmark modeling activities

    SciTech Connect

    Arguello, J. Guadalupe

    2015-08-01

    Sandia is participating in the third phase of an is a contributing partner to a U.S.-German "Joint Project" entitled "Comparison of current constitutive models and simulation procedures on the basis of model calculations of the thermo-mechanical behavior and healing of rock salt." The first goal of the project is to check the ability of numerical modeling tools to correctly describe the relevant deformation phenomena in rock salt under various influences. Achieving this goal will lead to increased confidence in the results of numerical simulations related to the secure storage of radioactive wastes in rock salt, thereby enhancing the acceptance of the results. These results may ultimately be used to make various assertions regarding both the stability analysis of an underground repository in salt, during the operating phase, and the long-term integrity of the geological barrier against the release of harmful substances into the biosphere, in the post-operating phase.

  3. Identifying tier one key suppliers.

    PubMed

    Wicks, Steve

    2013-01-01

    In today's global marketplace, businesses are becoming increasingly reliant on suppliers for the provision of key processes, activities, products and services in support of their strategic business goals. The result is that now, more than ever, the failure of a key supplier has potential to damage reputation, productivity, compliance and financial performance seriously. Yet despite this, there is no recognised standard or guidance for identifying a tier one key supplier base and, up to now, there has been little or no research on how to do so effectively. This paper outlines the key findings of a BCI-sponsored research project to investigate good practice in identifying tier one key suppliers, and suggests a scalable framework process model and risk matrix tool to help businesses effectively identify their tier one key supplier base.

  4. Results of Skylab medical experiment M171: Metabolic activity

    NASA Technical Reports Server (NTRS)

    Michel, E. L.; Rummel, J. A.; Sawin, C. F.; Buderer, M. C.; Lem, J. D.

    1974-01-01

    The experiment was conducted to establish whether man's ability to perform mechanical work would be progressively altered as a result of exposure to the weightless environment of space flight. The Skylab crewmen exercised on a bicycle ergometer at workloads approximating 25, 50, and 75 percent of their maximum aerobic capacity. The physiological parameters monitored were respiratory gas exchange, blood pressure, and vectorcardiogram/heart rate. The results of these tests indicate that the crewmen had no significant decrement in their responses to exercise during their exposure to zero gravity. The results of the third manned Skylab mission (Skylab 4) are presented and a comparison is made of the overall results obtained from the three successively longer Skylab manned missions. The Skylab 4 crewmembers' 84-day in-flight responses to exercise were no worse and were probably better than the responses of the crewmen on the first two Skylab missions. Indications that exercise was an important contributing factor in maintaining this response are discussed.

  5. Hydrophobic interactions as key determinants to the KCa3.1 channel closed configuration. An analysis of KCa3.1 mutants constitutively active in zero Ca2+.

    PubMed

    Garneau, Line; Klein, Hélène; Banderali, Umberto; Longpré-Lauzon, Ariane; Parent, Lucie; Sauvé, Rémy

    2009-01-02

    In this study we present evidence that residue Val282 in the S6 transmembrane segment of the calcium-activated KCa3.1 channel constitutes a key determinant of channel gating. A Gly scan of the S6 transmembrane segment first revealed that the substitutions A279G and V282G cause the channel to become constitutively active in zero Ca2+. Constitutive activity was not observed when residues extending from Cys276 to Ala286, other than Ala279 and Val282, were substituted to Gly. The accessibility of Cys engineered at Val275 deep in the channel cavity was next investigated for the ion-conducting V275C/V282G mutant and closed V275C channel in zero Ca2+ using Ag+ as probe. These experiments demonstrated that internal Ag+ ions have free access to the channel cavity independently of the channel conducting state, arguing against an activation gate located at the S6 segment C-terminal end. Experiments were also conducted where Val282 was substituted by residues differing in size and/or hydrophobicity. We found a strong correlation between constitutive activity in zero Ca2+ and the hydrophobic energy for side chain burial. Single channel recordings showed finally that constitutive activation in zero Ca2+ is better explained by a model where the channel is locked in a low conducting state with a high open probability rather than resulting from a change in the open/closed energy balance that would favor channel openings to a full conducting state in the absence of Ca2+. We conclude that hydrophobic interactions involving Val282 constitute key determinants to KCa3.1 gating by modulating the ion conducting state of the selectivity filter through an effect on the S6 transmembrane segment.

  6. The uses and results of active tetanus immunization

    PubMed Central

    Scheibel, Inga

    1955-01-01

    Both in animal experiments and in the course of two world wars active immunization has proved a safe method of protection against tetanus, and a method superior to passive serum prophylaxis. The three types of vaccine—plain, combined, and precipitated or adsorbed—all have their advantages and disadvantages, and the choice between them must be left to individual national health authorities. They should, however, be administered in two or three doses to confer basic immunity. What amount of circulating antitoxin is necessary to give full protection has not been accurately determined, but it is clear that one recall dose should be given about a year after the first injections as part of the routine course of injections. This seems enough to provide a long-lasting immunity, but a dose of vaccine should also be given at the time of injury. General immunization of the population is not practicable, but children, who are among the groups most at risk, can be immunized relatively simply by combined diphtheria and tetanus vaccine; in many countries, indeed, this is being done on an ever-increasing scale. PMID:13270078

  7. Current Results and Proposed Activities in Microgravity Fluid Dynamics

    NASA Technical Reports Server (NTRS)

    Polezhaev, V. I.

    1996-01-01

    The Institute for Problems in Mechanics' Laboratory work in mathematical and physical modelling of fluid mechanics develops models, methods, and software for analysis of fluid flow, instability analysis, direct numerical modelling and semi-empirical models of turbulence, as well as experimental research and verification of these models and their applications in technological fluid dynamics, microgravity fluid mechanics, geophysics, and a number of engineering problems. This paper presents an overview of the results in microgravity fluid dynamics research during the last two years. Nonlinear problems of weakly compressible and compressible fluid flows are discussed.

  8. Screening active components from Yu-ping-feng-san for regulating initiative key factors in allergic sensitization.

    PubMed

    Shen, Dandan; Xie, Xuejian; Zhu, Zhijie; Yu, Xi; Liu, Hailiang; Wang, Huizhu; Fan, Hongwei; Wang, Dawei; Jiang, Guorong; Hong, Min

    2014-01-01

    Yu-ping-feng-san (YPFS) is a Chinese medical formula that is used clinically for allergic diseases and characterized by reducing allergy relapse. Our previous studies demonstrated that YPFS efficiently inhibited T helper 2 cytokines in allergic inflammation. The underlying mechanisms of action of YPFS and its effective components remain unclear. In this study, it was shown that YPFS significantly inhibited production of thymic stromal lymphopoietin (TSLP), an epithelial cell-derived initiative factor in allergic inflammation, in vitro and in vivo. A method of human bronchial epithelial cell (16HBE) binding combined with HPLC-MS (named 16HBE-HPLC-MS) was established to explore potential active components of YPFS. The following five components bound to 16HBE cells: calycosin-7-glucoside, ononin, claycosin, sec-o-glucosylhamaudol and formononetin. Serum from YPFS-treated mice was analyzed and three major components were detected claycosin, formononetin and cimifugin. Among these, claycosin and formononetin were detected by 16HBE-HPLC-MS and in the serum of YPFS-treated mice. Claycosin and formononetin decreased the level of TSLP markedly at the initial stage of allergic inflammation in vivo. Nuclear factor (NF)-κB, a key transcription factor in TSLP production, was also inhibited by claycosin and formononetin, either in terms of transcriptional activation or its nuclear translocation in vitro. Allergic inflammation was reduced by claycosin and formononetin when they are administered only at the initial stage in a murine model of atopic contact dermatitis. Thus, epithelial cell binding combined with HPLC-MS is a valid method for screening active components from complex mixtures of Chinese medicine. It was demonstrated that the compounds screened from YPFS significantly attenuated allergic inflammation probably by reducing TSLP production via regulating NF-κB activation.

  9. AMP-activated kinase in human spermatozoa: identification, intracellular localization, and key function in the regulation of sperm motility.

    PubMed

    Calle-Guisado, Violeta; de Llera, Ana Hurtado; Martin-Hidalgo, David; Mijares, Jose; Gil, Maria C; Alvarez, Ignacio S; Bragado, Maria J; Garcia-Marin, Luis J

    2016-09-27

    AMP-activated kinase (AMPK), a protein that regulates energy balance and metabolism, has recently been identified in boar spermatozoa where regulates key functional sperm processes essential for fertilization. This work's aims are AMPK identification, intracellular localization, and their role in human spermatozoa function. Semen was obtained from healthy human donors. Sperm AMPK and phospho-Thr172-AMPK were analyzed by Western blotting and indirect immunofluorescence. High- and low-quality sperm populations were separated by a 40%-80% density gradient. Human spermatozoa motility was evaluated by an Integrated Semen Analysis System (ISAS) in the presence or absence of the AMPK inhibitor compound C (CC). AMPK is localized along the human spermatozoa, at the entire acrosome, midpiece and tail with variable intensity, whereas its active form, phospho-Thr172-AMPK, shows a prominent staining at the acrosome and sperm tail with a weaker staining in the midpiece and the postacrosomal region. Interestingly, spermatozoa bearing an excess residual cytoplasm show strong AMPK staining in this subcellular compartment. Both AMPK and phospho-Thr172-AMPK human spermatozoa contents exhibit important individual variations. Moreover, active AMPK is predominant in the high motility sperm population, where shows a stronger intensity compared with the low motility sperm population. Inhibition of AMPK activity in human spermatozoa by CC treatment leads to a significant reduction in any sperm motility parameter analyzed: percent of motile sperm, sperm velocities, progressivity, and other motility coefficients. This work identifies and points out AMPK as a new molecular mechanism involved in human spermatozoa motility. Further AMPK implications in the clinical efficiency of assisted reproduction and in other reproductive areas need to be studied.

  10. Preliminary results and future activities at the GARFIELD apparatus

    NASA Astrophysics Data System (ADS)

    Gramegna, F.; Mastinu, P. F.; Vannucci, L.; Bruno, M.; D'Agostino, M.; Fiandri, L.; Lanchais, A.; Vannini, G.; Casini, G.; Chiari, M.; Nannini, A.; Bonasera, A.; Cavallaro, S.; Cosmano, A.; Moroni, A.; Ordine, A.; Abbondanno, U.; Milazzo, P. M.; Margagliotti, G. M.

    2002-01-01

    A new apparatus has been designed and built to study reaction mechanisms in the energy regime of the ALPI linear accelerator of the Laboratori Nazionali di Legnaro (E/A = 5 - 20 MeV). In this paper the importance of studying these mechanisms will be underlined, no more as a problem limited to a narrow energy range or a single process, but as a continuous trend from low to high energies and from the physics of stable nuclei to that one regarding instabilities. With this remarks in mind, a first experiment has been performed studying the reaction 32S+58Ni at 11AMeV. Preliminary results show that important information can be derived on multi-body emission, which can contribute to renew the interest in this energy regime.

  11. Mapping of transcription factor motifs in active chromatin identifies IRF5 as key regulator in classical Hodgkin lymphoma

    PubMed Central

    Kreher, Stephan; Bouhlel, M. Amine; Cauchy, Pierre; Lamprecht, Björn; Li, Shuang; Grau, Michael; Hummel, Franziska; Köchert, Karl; Anagnostopoulos, Ioannis; Jöhrens, Korinna; Hummel, Michael; Hiscott, John; Wenzel, Sören-Sebastian; Lenz, Peter; Schneider, Markus; Küppers, Ralf; Scheidereit, Claus; Giefing, Maciej; Siebert, Reiner; Rajewsky, Klaus; Lenz, Georg; Cockerill, Peter N.; Janz, Martin; Dörken, Bernd; Bonifer, Constanze; Mathas, Stephan

    2014-01-01

    Deregulated transcription factor (TF) activities are commonly observed in hematopoietic malignancies. Understanding tumorigenesis therefore requires determining the function and hierarchical role of individual TFs. To identify TFs central to lymphomagenesis, we identified lymphoma type-specific accessible chromatin by global mapping of DNaseI hypersensitive sites and analyzed enriched TF-binding motifs in these regions. Applying this unbiased approach to classical Hodgkin lymphoma (HL), a common B-cell–derived lymphoma with a complex pattern of deregulated TFs, we discovered interferon regulatory factor (IRF) sites among the top enriched motifs. High-level expression of the proinflammatory TF IRF5 was specific to HL cells and crucial for their survival. Furthermore, IRF5 initiated a regulatory cascade in human non-Hodgkin B-cell lines and primary murine B cells by inducing the TF AP-1 and cooperating with NF-κB to activate essential characteristic features of HL. Our strategy efficiently identified a lymphoma type-specific key regulator and uncovered a tumor promoting role of IRF5. PMID:25288773

  12. Active Pin1 is a key target of all-trans retinoic acid in acute promyelocytic leukemia and breast cancer

    PubMed Central

    Wei, Shuo; Kozono, Shingo; Kats, Lev; Nechama, Morris; Li, Wenzong; Guarnerio, Jlenia; Luo, Manli; You, Mi-Hyeon; Yao, Yandan; Kondo, Asami; Hu, Hai; Bozkurt, Gunes; Moerke, Nathan J.; Cao, Shugeng; Reschke, Markus; Chen, Chun-Hau; Rego, Eduardo M.; LoCoco, Francesco; Cantley, Lewis; Lee, Tae Ho; Wu, Hao; Zhang, Yan; Pandolfi, Pier Paolo; Zhou, Xiao Zhen; Lu, Kun Ping

    2015-01-01

    A common key regulator of oncogenic signaling pathways in multiple tumor types is the unique isomerase Pin1. However, available Pin1 inhibitors lack the required specificity and potency. Using mechanism-based screening, here we find that all-trans retinoic acid (ATRA)--a therapy for acute promyelocytic leukemia (APL) that is considered the first example of targeted therapy in cancer, but its drug target remains elusive--inhibits and degrades active Pin1 selectively in cancer cells by directly binding to the substrate phosphate- and proline-binding pockets in the Pin1 active site. ATRA-induced Pin1 ablation degrades the fusion oncogene PML-RARα and treats APL in cell and animal models and human patients. ATRA-induced Pin1 ablation also inhibits triple negative breast cancer cell growth in human cells and in animal models by acting on many Pin1 substrate oncogenes and tumor suppressors. Thus, ATRA simultaneously blocks multiple Pin1-regulated cancer-driving pathways, an attractive property for treating aggressive and drug-resistant tumors. PMID:25849135

  13. Mapping of transcription factor motifs in active chromatin identifies IRF5 as key regulator in classical Hodgkin lymphoma.

    PubMed

    Kreher, Stephan; Bouhlel, M Amine; Cauchy, Pierre; Lamprecht, Björn; Li, Shuang; Grau, Michael; Hummel, Franziska; Köchert, Karl; Anagnostopoulos, Ioannis; Jöhrens, Korinna; Hummel, Michael; Hiscott, John; Wenzel, Sören-Sebastian; Lenz, Peter; Schneider, Markus; Küppers, Ralf; Scheidereit, Claus; Giefing, Maciej; Siebert, Reiner; Rajewsky, Klaus; Lenz, Georg; Cockerill, Peter N; Janz, Martin; Dörken, Bernd; Bonifer, Constanze; Mathas, Stephan

    2014-10-21

    Deregulated transcription factor (TF) activities are commonly observed in hematopoietic malignancies. Understanding tumorigenesis therefore requires determining the function and hierarchical role of individual TFs. To identify TFs central to lymphomagenesis, we identified lymphoma type-specific accessible chromatin by global mapping of DNaseI hypersensitive sites and analyzed enriched TF-binding motifs in these regions. Applying this unbiased approach to classical Hodgkin lymphoma (HL), a common B-cell-derived lymphoma with a complex pattern of deregulated TFs, we discovered interferon regulatory factor (IRF) sites among the top enriched motifs. High-level expression of the proinflammatory TF IRF5 was specific to HL cells and crucial for their survival. Furthermore, IRF5 initiated a regulatory cascade in human non-Hodgkin B-cell lines and primary murine B cells by inducing the TF AP-1 and cooperating with NF-κB to activate essential characteristic features of HL. Our strategy efficiently identified a lymphoma type-specific key regulator and uncovered a tumor promoting role of IRF5.

  14. Results of mobile gamma scanning activities in Tonawanda, New York

    SciTech Connect

    Cottrell, W.D.; Witt, D.A.; Rodriguez, R.E.; Carrier, R.F.

    1990-12-01

    During the 1940s, the Linde Air Products Division of Union Carbide operated a plant in Tonawanda, New York, for the Manhattan Engineer District (MED) and the Atomic Energy Commission (AEC). Uranium production and some nickel processing were conducted at the site. It is the policy of the US Department of Energy (DOE) to verify that radiological conditions at such sites or facilities comply with current DOE guidelines. Guidelines for release and use of such sites have become more stringent as research has provided more information since previous cleanups. The Formerly Utilized Sites Remedial Action Program (FUSRAP) was established as part of that effort to confirm the closeout status of facilities under contract to agencies preceding DOE during early nuclear energy development. Under the FUSRAP program, the Linde site itself has been previously investigated to determine the extent of on-site radiological contamination. As a precaution to insure that no residual radioactive materials were transported off-site, the Department of Energy requested that ORNL survey the area in the vicinity of the Linde Plant, the waste water treatment facility on Tower Road, the Sheridan Park Fire Station (District 4), and the Tonawanda Landfill to assess whether any residual radioactive material could be detected. The survey was conducted the week of April 3, 1990. Results of analysis of soil samples from the Tonawanda Landfill revealed slightly elevated concentrations of {sup 238}U and {sup 226}Ra suggestive of residuals from former Linde Plant operations. Therefore, it is recommended that additional surveying of the landfill property and of Sheridan Creek from south of the Linde property to its confluence with the Niagara River be conducted. The survey should include the measurement of gamma radiation levels and radionuclide analysis of silt samples. 6 refs., 4 figs., 1 tab.

  15. Key results of the mini-dome Fresnel lens concentrator array development program under recently completed NASA and SDIO SBIR projects

    NASA Technical Reports Server (NTRS)

    Oneill, Mark J.; Piszczor, Michael F.; Fraas, Lewis M.

    1991-01-01

    Since 1986, ENTECH and the NASA Lewis Research Center have been developing a new photovoltaic concentrator system for space power applications. The unique refractive system uses small, dome shaped Fresnel lenses to focus sunlight onto high efficiency photovoltaic concentrator cells which use prismatic cell covers to further increase their performance. Highlights of the five-year development include near Air Mass Zero (AM0) Lear Jet flight testing of mini-dome lenses (90 pct. net optical efficiency achieved); tests verifying sun-pointing error tolerance with negligible power loss; simulator testing of prism-covered GaAs concentrator cells (24 pct. AM0 efficiency); testing of prism-covered Boeing GaAs/GaSb tandem cells (31 pct. AM0 efficiency); and fabrication and outdoor testing of a 36-lens/cell element panel. These test results have confirmed previous analytical predictions which indicate substantial performance improvements for this technology over current array systems. Based on program results to date, it appears than an array power density of 300 watts/sq m and a specific power of 100 watts/kg can be achieved in the near term. All components of the array appear to be readily manufacturable from space-durable materials at reasonable cost. A concise review is presented of the key results leading to the current array, and further development plans for the future are briefly discussed.

  16. Results.

    ERIC Educational Resources Information Center

    Zemsky, Robert; Shaman, Susan; Shapiro, Daniel B.

    2001-01-01

    Describes the Collegiate Results Instrument (CRI), which measures a range of collegiate outcomes for alumni 6 years after graduation. The CRI was designed to target alumni from institutions across market segments and assess their values, abilities, work skills, occupations, and pursuit of lifelong learning. (EV)

  17. Structural characterization of native autoinducing peptides and abiotic analogues reveals key features essential for activation and inhibition of an AgrC quorum sensing receptor in Staphylococcus aureus.

    PubMed

    Tal-Gan, Yftah; Ivancic, Monika; Cornilescu, Gabriel; Cornilescu, Claudia C; Blackwell, Helen E

    2013-12-11

    Staphylococcus aureus is a major human pathogen that uses quorum sensing (QS) to control virulence. Its QS system is regulated by macrocyclic peptide signals (or autoinducing peptides (AIPs)) and their cognate transmembrane receptors (AgrCs). Four different specificity groups of S. aureus have been identified to date (groups I-IV), each of which uses a different AIP:AgrC pair. Non-native ligands capable of intercepting AIP:AgrC binding, and thereby QS, in S. aureus have attracted considerable interest as chemical tools to study QS pathways and as possible antivirulence strategies for the treatment of infection. We recently reported a set of analogues of the group-III AIP that are capable of strongly modulating the activity of all four AgrC receptors. Critical to the further development of such ligands is a detailed understanding of the structural features of both native AIPs and non-native analogues that are essential for activity. Herein, we report the first three-dimensional structural analysis of the known native AIP signals (AIPs-I-IV) and several AIP-III analogues with varied biological activities using NMR spectroscopy. Integration of these NMR studies with the known agonism and antagonism profiles of these peptides in AgrC-III revealed two key structural elements that control AIP-III (and non-native peptide) activity: (1) a tri-residue hydrophobic "knob" essential for both activation and inhibition and (2) a fourth anchor point on the exocyclic tail needed for receptor activation. These results provide strong structural support for a mechanism of AIP-mediated AgrC activation and inhibition in S. aureus , and should facilitate the design of new AgrC ligands with enhanced activities (as agonists or antagonists) and simplified chemical structures.

  18. Identification of key functional residues in the active site of human {beta}1,4-galactosyltransferase 7: a major enzyme in the glycosaminoglycan synthesis pathway.

    PubMed

    Talhaoui, Ibtissam; Bui, Catherine; Oriol, Rafael; Mulliert, Guillermo; Gulberti, Sandrine; Netter, Patrick; Coughtrie, Michael W H; Ouzzine, Mohamed; Fournel-Gigleux, Sylvie

    2010-11-26

    Glycosaminoglycans (GAGs) play a central role in many pathophysiological events, and exogenous xyloside substrates of β1,4-galactosyltransferase 7 (β4GalT7), a major enzyme of GAG biosynthesis, have interesting biomedical applications. To predict functional peptide regions important for substrate binding and activity of human β4GalT7, we conducted a phylogenetic analysis of the β1,4-galactosyltransferase family and generated a molecular model using the x-ray structure of Drosophila β4GalT7-UDP as template. Two evolutionary conserved motifs, (163)DVD(165) and (221)FWGWGREDDE(230), are central in the organization of the enzyme active site. This model was challenged by systematic engineering of point mutations, combined with in vitro and ex vivo functional assays. Investigation of the kinetic properties of purified recombinant wild-type β4GalT7 and selected mutants identified Trp(224) as a key residue governing both donor and acceptor substrate binding. Our results also suggested the involvement of the canonical carboxylate residue Asp(228) acting as general base in the reaction catalyzed by human β4GalT7. Importantly, ex vivo functional tests demonstrated that regulation of GAG synthesis is highly responsive to modification of these key active site amino acids. Interestingly, engineering mutants at position 224 allowed us to modify the affinity and to modulate the specificity of human β4GalT7 toward UDP-sugars and xyloside acceptors. Furthermore, the W224H mutant was able to sustain decorin GAG chain substitution but not GAG synthesis from exogenously added xyloside. Altogether, this study provides novel insight into human β4GalT7 active site functional domains, allowing manipulation of this enzyme critical for the regulation of GAG synthesis. A better understanding of the mechanism underlying GAG assembly paves the way toward GAG-based therapeutics.

  19. Exogenous ceramide-1-phosphate (C1P) and phospho-ceramide analogue-1 (PCERA-1) regulate key macrophage activities via distinct receptors

    PubMed Central

    Katz, Sebastián; Ernst, Orna; Avni, Dorit; Athamna, Muhammad; Philosoph, Amir; Arana, Lide; Ouro, Alberto; Hoeferlin, L. Alexis; Meijler, Michael M.; Chalfant, Charles E.; Gómez-Muñoz, Antonio; Zor, Tsaffrir

    2016-01-01

    Inflammation is an ensemble of tightly regulated steps, in which macrophages play an essential role. Previous reports showed that the natural sphingolipid ceramide 1-phosphate (C1P) stimulates macrophages migration, while the synthetic C1P mimic, phospho-ceramide analogue-1 (PCERA-1), suppresses production of the key pro-inflammatory cytokine TNFα and amplifies production of the key anti-inflammatory cytokine IL-10 in LPS-stimulated macrophages, via one or more unidentified G-protein coupled receptors. We show that C1P stimulated RAW264.7 macrophages migration via the NFκB pathway and MCP-1 induction, while PCERA-1 neither mimicked nor antagonized these activities. Conversely, PCERA-1 synergistically elevated LPS-dependent IL-10 expression in RAW264.7 macrophages via the cAMP-PKA-CREB signaling pathway, while C1P neither mimicked nor antagonized these activities. Interestingly, both compounds have the capacity to additively inhibit TNFα secretion; PCERA-1, but not C1P, suppressed LPS-induced TNFα expression in macrophages in a CREB-dependent manner, while C1P, but not PCERA-1, directly inhibited recombinant TNFα converting enzyme (TACE). Finally, PCERA-1 failed to interfere with binding of C1P to either the cell surface receptor or to TACE. These results thus indicate that the natural sphingolipid C1P and its synthetic analog PCERA-1 bind and activate distinct receptors expressed in RAW264.7 macrophages. Identification of these receptors will be instrumental for elucidation of novel activities of extra-cellular sphingolipids, and may pave the way for the design of new sphingolipid mimics for the treatment of inflammatory diseases, and pathologies which depend on cell migration, as in metastatic tumors. PMID:26656944

  20. A survey of Lab Tests Online-UK users: a key resource for patients to empower and help them understand their laboratory test results.

    PubMed

    Leyland, Rebecca; Freedman, Danielle B

    2016-11-01

    Background Lab Tests Online-UK celebrated its 10th anniversary in 2014 and to mark the occasion the first comprehensive survey of website users was undertaken. Methods A pop-up box with a link to Survey Monkey was used to offer website users the chance to participate in the survey, which was live from 4 March 2014 to 11 April 2014. Results Six hundred and sixty-one participants started the questionnaire and 338 completed all of the demographic questions. Although the website is designed and aimed at patients and the public, a significant number of respondents were health-care professionals (47%). The majority of survey participants found the Lab Tests Online-UK website via a search engine and were visiting the site for themselves. The majority of participants found what they were looking for on the website and found the information very easy or fairly easy to understand. The patient respondents were keen to see their laboratory test results (87%), but the majority did not have access (60%) at the time of the survey. Conclusions This survey provides good evidence that the Lab Tests Online-UK website is a useful resource for patients and health-care professionals alike. It comes at a poignant time as the release of results direct to patients starts with access to their medical records. The Lab Tests Online-UK website has a key role in enabling patients to understand their lab test results, and therefore empowering them to take an interest and engage in their own healthcare.

  1. Waste-Activated Sludge Fermentation for Polyacrylamide Biodegradation Improved by Anaerobic Hydrolysis and Key Microorganisms Involved in Biological Polyacrylamide Removal

    PubMed Central

    Dai, Xiaohu; Luo, Fan; Zhang, Dong; Dai, Lingling; Chen, Yinguang; Dong, Bin

    2015-01-01

    During the anaerobic digestion of dewatered sludge, polyacrylamide (PAM), a chemical conditioner, can usually be consumed as a carbon and nitrogen source along with other organic matter (e.g., proteins and carbohydrates in the sludge). However, a significant accumulation of acrylamide monomers (AMs) was observed during the PAM biodegradation process. To improve the anaerobic hydrolysis of PAM, especially the amide hydrolysis process, and to avoid the generation of the intermediate product AM, a new strategy is reported herein that uses an initial pH of 9, 200 mg COD/L of PAM and a fermentation time of 17 d. First, response surface methodology (RSM) was applied to optimize PAM removal in the anaerobic digestion of the sludge. The biological hydrolysis of PAM reached 86.64% under the optimal conditions obtained from the RSM. Then, the mechanisms for the optimized parameters that significantly improved the biological hydrolysis of PAM were investigated by the synergistic effect of the main organic compounds in the sludge, the floc size distribution, and the enzymatic activities. Finally, semi-continuous-flow experiments for a microbial community study were investigated based on the determination of key microorganisms involved in the biological hydrolysis of PAM. PMID:26144551

  2. RNA interference (RNAi)-induced suppression of nicotine demethylase activity reduces levels of a key carcinogen in cured tobacco leaves.

    PubMed

    Lewis, Ramsey S; Jack, Anne M; Morris, Jerry W; Robert, Vincent J M; Gavilano, Lily B; Siminszky, Balazs; Bush, Lowell P; Hayes, Alec J; Dewey, Ralph E

    2008-05-01

    Technologies for reducing the levels of tobacco product constituents that may contribute to unwanted health effects are desired. Target compounds include tobacco-specific nitrosamines (TSNAs), a class of compounds generated through the nitrosation of pyridine alkaloids during the curing and processing of tobacco. Studies have reported the TSNA N'-nitrosonornicotine (NNN) to be carcinogenic in laboratory animals. NNN is formed via the nitrosation of nornicotine, a secondary alkaloid produced through enzymatic N-demethylation of nicotine. Strategies to lower nornicotine levels in tobacco (Nicotiana tabacum L.) could lead to a corresponding decrease in NNN accumulation in cured leaves. The major nicotine demethylase gene of tobacco has recently been isolated. In this study, a large-scale field trial was conducted to evaluate transgenic lines of burley tobacco carrying an RNA interference (RNAi) construct designed to inhibit the expression of this gene. Selected transgenic lines exhibited a six-fold decrease in nornicotine content relative to untransformed controls. Analysis of cured leaves revealed a commensurate decrease in NNN and total TSNAs. The inhibition of nicotine demethylase activity is an effective means of decreasing significantly the level of a key defined animal carcinogen present in tobacco products.

  3. BRCA1 is a key regulator of breast differentiation through activation of Notch signalling with implications for anti-endocrine treatment of breast cancers

    PubMed Central

    Buckley, Niamh E.; Nic An tSaoir, Caoimhe B.; Blayney, Jaine K.; Oram, Lisa C.; Crawford, Nyree T.; D’Costa, Zenobia C.; Quinn, Jennifer E.; Kennedy, Richard D.; Harkin, D. Paul; Mullan, Paul B.

    2013-01-01

    Here, we show for the first time, that the familial breast/ovarian cancer susceptibility gene BRCA1 activates the Notch pathway in breast cells by transcriptional upregulation of Notch ligands and receptors in both normal and cancer cells. We demonstrate through chromatin immunoprecipitation assays that BRCA1 is localized to a conserved intronic enhancer region within the Notch ligand Jagged-1 (JAG1) gene, an event requiring ΔNp63. We propose that this BRCA1/ΔNp63-mediated induction of JAG1 may be important the regulation of breast stem/precursor cells, as knockdown of all three proteins resulted in increased tumoursphere growth and increased activity of stem cell markers such as Aldehyde Dehydrogenase 1 (ALDH1). Knockdown of Notch1 and JAG1 phenocopied BRCA1 knockdown resulting in the loss of Estrogen Receptor-α (ER-α) expression and other luminal markers. A Notch mimetic peptide could activate an ER-α promoter reporter in a BRCA1-dependent manner, whereas Notch inhibition using a γ-secretase inhibitor reversed this process. We demonstrate that inhibition of Notch signalling resulted in decreased sensitivity to the anti-estrogen drug Tamoxifen but increased expression of markers associated with basal-like breast cancer. Together, these findings suggest that BRCA1 transcriptional upregulation of Notch signalling is a key event in the normal differentiation process in breast tissue. PMID:23863842

  4. Small-scale home composting of biodegradable household waste: overview of key results from a 3-year research programme in West London.

    PubMed

    Smith, Stephen R; Jasim, Sharon

    2009-12-01

    Home composting (HC) is recognized by both local and national Governments for its contribution to reducing household waste disposal in landfill. However, the quantitative impact of HC on the diversion of household waste from landfill is uncertain. An overview of key results is presented from a 3-year research programme on HC in the West London area of Runnymede Borough Council (RBC), Surrey, UK. The amount of biodegradable household waste diverted from landfill disposal by HC was measured in a 2-year monitoring study involving 64 homeowners. The total average annual waste input to a standard 290 L HC bin was approximately 370 kg per household. The average relative mass inputs of kitchen, paper and garden waste were 29, 2 and 69%, respectively. A survey of the study area indicated that approximately 20% of households were engaged in HC and, based on inputs to HC bins, this corresponded to an overall recycling/diversion rate equivalent to 20% of household biodegradable waste. Temperature and gas composition measurements indicated organic matter decomposition by HC was aerobic and only traces of CH(4) were occasionally detected. A field trial examined the end-use of composted products for the growth of Petunia grandiflora. Flower production increased with home-produced composts in comparison with peat-amended or untreated control soil. Compost chemical composition, bioaerosol emissions and vector attraction were also investigated.

  5. Behavior Change After 20 Months of a Radio Campaign Addressing Key Lifesaving Family Behaviors for Child Survival: Midline Results From a Cluster Randomized Trial in Rural Burkina Faso

    PubMed Central

    Sarrassat, Sophie; Meda, Nicolas; Ouedraogo, Moctar; Some, Henri; Bambara, Robert; Head, Roy; Murray, Joanna; Remes, Pieter; Cousens, Simon

    2015-01-01

    Background: In Burkina Faso, a comprehensive 35-month radio campaign addressed key, multiple family behaviors for improving under-5 child survival and was evaluated using a repeated cross-sectional, cluster randomized design. The primary outcome of the trial was postneonatal under-5 child mortality. This paper reports on behavior change achieved at midline. Method: Fourteen community radio stations in 14 geographic areas were selected based on their high listenership. Seven areas were randomly allocated to receive the intervention while the other 7 areas served as controls. The campaign was launched in March 2012. Cross-sectional surveys of about 5,000 mothers of under-5 children, living in villages close to the radio stations, were conducted at baseline (from December 2011 to February 2012) and at midline (in November 2013), after 20 months of campaigning. Statistical analyses were based on cluster-level summaries using a difference-in-difference (DiD) approach and adjusted for imbalances between arms at baseline. In addition, routine health facility data were analyzed for evidence of changes in health facility utilization. Results: At midline, 75% of women in the intervention arm reported recognizing radio spots from the campaign. There was some evidence of the campaign having positive effects on care seeking for diarrhea (adjusted DiD, 17.5 percentage points; 95% confidence interval [CI], 2.5 to 32.5; P = .03), antibiotic treatment for fast/difficult breathing (adjusted DiD, 29.6 percentage points; 95% CI, 3.5 to 55.7; P = .03), and saving money during pregnancy (adjusted DiD, 12.8 percentage points; 95% CI, 1.4 to 24.2; P = .03). For other target behaviors, there was little or no evidence of an impact of the campaign after adjustment for baseline imbalances and confounding factors. There was weak evidence of a positive correlation between the intensity of broadcasting of messages and reported changes in target behaviors. Routine health facility data

  6. Simple and robust determination of the activity signature of key carbohydrate metabolism enzymes for physiological phenotyping in model and crop plants.

    PubMed

    Jammer, Alexandra; Gasperl, Anna; Luschin-Ebengreuth, Nora; Heyneke, Elmien; Chu, Hyosub; Cantero-Navarro, Elena; Großkinsky, Dominik K; Albacete, Alfonso A; Stabentheiner, Edith; Franzaring, Jürgen; Fangmeier, Andreas; van der Graaff, Eric; Roitsch, Thomas

    2015-09-01

    The analysis of physiological parameters is important to understand the link between plant phenotypes and their genetic bases, and therefore is needed as an important element in the analysis of model and crop plants. The activities of enzymes involved in primary carbohydrate metabolism have been shown to be strongly associated with growth performance, crop yield, and quality, as well as stress responses. A simple, fast, and cost-effective method to determine activities for 13 key enzymes involved in carbohydrate metabolism has been established, mainly based on coupled spectrophotometric kinetic assays. The comparison of extraction buffers and requirement for dialysis of crude protein extracts resulted in a universal protein extraction protocol, suitable for the preparation of protein extracts from different organs of various species. Individual published kinetic activity assays were optimized and adapted for a semi-high-throughput 96-well assay format. These assays proved to be robust and are thus suitable for physiological phenotyping, enabling the characterization and diagnosis of the physiological state. The potential of the determination of distinct enzyme activity signatures as part of a physiological fingerprint was shown for various organs and tissues from three monocot and five dicot model and crop species, including two case studies with external stimuli. Differential and specific enzyme activity signatures are apparent during inflorescence development and upon in vitro cold treatment of young inflorescences in the monocot ryegrass, related to conditions for doubled haploid formation. Likewise, treatment of dicot spring oilseed rape with elevated CO2 concentration resulted in distinct patterns of enzyme activity responses in leaves.

  7. Starting Right: Using "Biophilia," Organism Cards, & Key Themes in Biology to Introduce Student-Centered Active-Learning Strategies at the Beginning of a Course

    ERIC Educational Resources Information Center

    Metzger, Kelsey

    2013-01-01

    To create rich learning experiences, it is important to engage students from the very beginning of a course and lay the foundation for constructing a community of active learners. The activities described here using "organism cards" connect students' previous knowledge to course goals and address key themes in biology while initiating…

  8. Hydathode trichomes actively secreting water from leaves play a key role in the physiology and evolution of root-parasitic rhinanthoid Orobanchaceae

    PubMed Central

    Světlíková, Petra; Hájek, Tomáš; Těšitel, Jakub

    2015-01-01

    Background and Aims Root hemiparasites from the rhinanthoid clade of Orobanchaceae possess metabolically active glandular trichomes that have been suggested to function as hydathode trichomes actively secreting water, a process that may facilitate resource acquisition from the host plant’s root xylem. However, no direct evidence relating the trichomes to water secretion exists, and carbon budgets associated with this energy-demanding process have not been determined. Methods Macro- and microscopic observations of the leaves of hemiparasitic Rhinanthus alectorolophus were conducted and night-time gas exchange was measured. Correlations were examined among the intensity of guttation, respiration and transpiration, and analysis of these correlations allowed the carbon budget of the trichome activity to be quantified. We examined the intensity of guttation, respiration and transpiration, correlations among which indicate active water secretion. Key Results Guttation was observed on the leaves of 50 % of the young, non-flowering plants that were examined, and microscopic observations revealed water secretion from the glandular trichomes present on the abaxial leaf side. Night-time rates of respiration and transpiration and the presence of guttation drops were positively correlated, which is a clear indicator of hydathode trichome activity. Subsequent physiological measurements on older, flowering plants indicated neither intense guttation nor the presence of correlations, which suggests that the peak activity of hydathodes is in the juvenile stage. Conclusions This study provides the first unequivocal evidence for the physiological role of the hydathode trichomes in active water secretion in the rhinanthoid Orobanchaceae. Depending on the concentration of organic elements calculated to be in the host xylem sap, the direct effect of water secretion on carbon balance ranges from close to neutral to positive. However, it is likely to be positive in the xylem-only feeding

  9. Novel mechanisms for superoxide-scavenging activity of human manganese superoxide dismutase determined by the K68 key acetylation site.

    PubMed

    Lu, Jiaqi; Cheng, Kuoyuan; Zhang, Bo; Xu, Huan; Cao, Yuanzhao; Guo, Fei; Feng, Xudong; Xia, Qing

    2015-08-01

    Superoxide is the primary reactive oxygen species generated in the mitochondria. Manganese superoxide dismutase (SOD2) is the major enzymatic superoxide scavenger present in the mitochondrial matrix and one of the most crucial reactive oxygen species-scavenging enzymes in the cell. SOD2 is activated by sirtuin 3 (SIRT3) through NAD(+)-dependent deacetylation. However, the exact acetylation sites of SOD2 are ambiguous and the mechanisms underlying the deacetylation-mediated SOD2 activation largely remain unknown. We are the first to characterize SOD2 mutants of the acetylation sites by investigating the relative enzymatic activity, structures, and electrostatic potential of SOD2 in this study. These SOD2 mutations affected the superoxide-scavenging activity in vitro and in HEK293T cells. The lysine 68 (K68) site is the most important acetylation site contributing to SOD2 activation and plays a role in cell survival after paraquat treatment. The molecular basis underlying the regulation of SOD2 activity by K68 was investigated in detail. Molecular dynamics simulations revealed that K68 mutations induced a conformational shift of residues located in the active center of SOD2 and altered the charge distribution on the SOD2 surface. Thus, the entry of the superoxide anion into the coordinated core of SOD2 was inhibited. Our results provide a novel mechanistic insight, whereby SOD2 acetylation affects the structure and charge distribution of SOD2, its tetramerization, and p53-SOD2 interactions of SOD2 in the mitochondria, which may play a role in nuclear-mitochondrial communication during aging.

  10. Oxidative stress status accompanying diabetic bladder cystopathy results in the activation of protein degradation pathways

    PubMed Central

    Kanika, Nirmala; Chang, Jinsook; Tong, Yuehong; Tiplitsky, Scott; Lin, Juan; Yohannes, Elizabeth; Tar, Moses; Chance, Mark; Christ, George J.; Melman, Arnold; Davies, Kelvin

    2010-01-01

    Objectives To investigate the role that oxidative stress plays in the development of diabetic cystopathy. Materials and methods Comparative gene expression in the bladder of non-diabetic and streptozotocin (STZ)-induced 2-month-old diabetic rats was carried out using microarray analysis. Evidence of oxidative stress was investigated in the bladder by analyzing glutathione S-transferase activity, lipid peroxidation, and carbonylation and nitrosylation of proteins. The activity of protein degradation pathways was assessed using western blot analysis. Results Analysis of global gene expression showed that detrusor smooth muscle tissue of STZ-induced diabetes undergoes significant enrichment in targets involved in the production or regulation of reactive oxygen species (P = 1.27 × 10−10). The microarray analysis was confirmed by showing that markers of oxidative stress were all significantly increased in the diabetic bladder. It was hypothesized that the sequelae to oxidative stress would be increased protein damage and apoptosis. This was confirmed by showing that two key proteins involved in protein degradation (Nedd4 and LC3B) were greatly up-regulated in diabetic bladders compared to controls by 12.2 ± 0.76 and 4.4 ± 1.0-fold, respectively, and the apoptosis inducing protein, BAX, was up-regulated by 6.76 ± 0.76-fold. Conclusions Overall, the findings obtained in the present study add to the growing body of evidence showing that diabetic cystopathy is associated with oxidative damage of smooth muscle cells, and results in protein damage and activation of apoptotic pathways that may contribute to a deterioration in bladder function. PMID:21518418

  11. Key role of persistent free radicals in hydrogen peroxide activation by biochar: implications to organic contaminant degradation.

    PubMed

    Fang, Guodong; Gao, Juan; Liu, Cun; Dionysiou, Dionysios D; Wang, Yu; Zhou, Dongmei

    2014-01-01

    We investigated the activation of hydrogen peroxide (H2O2) by biochars (produced from pine needles, wheat, and maize straw) for 2-chlorobiphenyl (2-CB) degradation in the present study. It was found that H2O2 can be effectively activated by biochar, which produces hydroxyl radical ((•)OH) to degrade 2-CB. Furthermore, the activation mechanism was elucidated by electron paramagnetic resonance (EPR) and salicylic acid (SA) trapping techniques. The results showed that biochar contains persistent free radicals (PFRs), typically ∼ 10(18) unpaired spins/gram. Higher trapped [(•)OH] concentrations were observed with larger decreases in PFRs concentration, when H2O2 was added to biochar, indicating that PFRs were the main contributor to the formation of (•)OH. This hypothesis was supported by the linear correlations between PFRs concentration and trapped [(•)OH], as well as kobs of 2-CB degradation. The correlation coefficients (R(2)) were 0.723 and 0.668 for PFRs concentration vs trapped [(•)OH], and PFRs concentration vs kobs, respectively, when all biochars pyrolyzed at different temperatures were included. For the same biochar washed by different organic solvents (methanol, hexane, dichloromethane, and toluene), the correlation coefficients markedly increased to 0.818-0.907. Single-electron transfer from PFRs to H2O2 was a possible mechanism for H2O2 activation by biochars, which was supported by free radical quenching studies. The findings of this study provide a new pathway for biochar implication and insight into the mechanism of H2O2 activation by carbonaceous materials (e.g., activated carbon and graphite).

  12. Dogs motivate obese children for physical activity: key elements of a motivational theory of animal-assisted interventions

    PubMed Central

    Wohlfarth, Rainer; Mutschler, Bettina; Beetz, Andrea; Kreuser, Friederike; Korsten-Reck, Ulrike

    2013-01-01

    Background: There is empirical evidence that the presence of a companion animal can have a positive impact on performance. The available evidence can be viewed in terms of differing hypotheses that attempt to explain the mechanisms behind the positive effects. Little attention has been given to motivation as a potential mode of action with regards to human-animal interactions. First we give an overview of evidence that animals might promote motivation. Second we present a study to examine the effect of a therapy dog on exercise performance in children with obesity. Methods: Twelve children, aged 8–12 years old, were randomly assigned to two groups in a crossover design: dog-group and human confederate group. Several types of physical activities via accelerometer and subjective ratings of wellbeing, satisfaction, and motivation were assessed. Data were analyzed using analysis of variance for repeated measures on one factor. Results: The main effect of condition was significant for all performance variables. There was less passive behavior and more physical activity for all performance variables in the presence of the dog than in that of the human confederate. Between dog- and human- condition there was no difference in the subjective rating of motivation, wellbeing, or satisfaction. Discussion: The results demonstrate that the presence of a therapy dog has the potential to increase physical activity in obese children. Task performance as a declarative measure was increased by the presence of the dog in comparison to a human confederate, but self-report measures of motivation, satisfaction or wellbeing did not differ between the two conditions. Therefore, it stands to reason that a dog could trigger implicit motives which enhance motivation for activity. The results of our study indicate the potentially beneficial effect of incorporating dogs into outpatient training for obese children. PMID:24194726

  13. Investigation of the Key Pharmacological Activities of Ficus racemosa and Analysis of Its Major Bioactive Polyphenols by HPLC-DAD

    PubMed Central

    Sumi, Salma Akter; Siraj, Md. Afjalus; Hossain, Amir; Mia, Md. Sagir; Afrin, Seagufta

    2016-01-01

    Objective. Oxidative stress leads to numerous physiological disorders including infectious diseases, inflammation, and cancer. The present study was carried out to investigate antioxidant, antibacterial, and cytotoxic activity of methanol crude extract of leaves and fruits of the Ficus racemosa (LCME and FCME, resp.) and to analyse its major bioactive polyphenols by HPLC-DAD. Methods. Antioxidant capacity of the extracts was evaluated by DPPH free radical scavenging, reducing power, total phenolic, total flavonoid, total tannin content assay, superoxide radical, hydroxyl radical, and hydrogen peroxide scavenging assay. Identification and quantification of bioactive polyphenols were done by HPLC-DAD method. Antibacterial activity was tested by “disc diffusion” method. Brine shrimp lethality assay was carried out to check the cytotoxic potential. Result. Both LCME and FCME showed DPPH scavenging ability and concentration dependent reducing power activity. They had phenolic content, flavonoid content, and tannin content. Both the extracts showed superoxide radical scavenging ability, hydroxyl radical scavenging ability, and hydrogen peroxide scavenging ability. HPLC analysis of LCME and FCME indicated the presence of significant amount of gallic acid along with other phenolic constituents. Conclusion. Significant amount of gallic acid along with other phenolic constituents might have played an important role in the observed antioxidant, antibacterial, and cytotoxic activity. PMID:28105059

  14. Macrolones Are a Novel Class of Macrolide Antibiotics Active against Key Resistant Respiratory Pathogens In Vitro and In Vivo

    PubMed Central

    Verbanac, Donatella; Padovan, Jasna; Dominis-Kramarić, Miroslava; Kelnerić, Željko; Perić, Mihaela; Banjanac, Mihailo; Ergović, Gabrijela; Simon, Nerrisa; Broskey, John; Holmes, David J.; Eraković Haber, Vesna

    2016-01-01

    As we face an alarming increase in bacterial resistance to current antibacterial chemotherapeutics, expanding the available therapeutic arsenal in the fight against resistant bacterial pathogens causing respiratory tract infections is of high importance. The antibacterial potency of macrolones, a novel class of macrolide antibiotics, against key respiratory pathogens was evaluated in vitro and in vivo. MIC values against Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, and Haemophilus influenzae strains sensitive to macrolide antibiotics and with defined macrolide resistance mechanisms were determined. The propensity of macrolones to induce the expression of inducible erm genes was tested by the triple-disk method and incubation in the presence of subinhibitory concentrations of compounds. In vivo efficacy was assessed in a murine model of S. pneumoniae-induced pneumonia, and pharmacokinetic (PK) profiles in mice were determined. The in vitro antibacterial profiles of macrolones were superior to those of marketed macrolide antibiotics, including the ketolide telithromycin, and the compounds did not induce the expression of inducible erm genes. They acted as typical protein synthesis inhibitors in an Escherichia coli transcription/translation assay. Macrolones were characterized by low to moderate systemic clearance, a large volume of distribution, a long half-life, and low oral bioavailability. They were highly efficacious in a murine model of pneumonia after intraperitoneal application even against an S. pneumoniae strain with constitutive resistance to macrolide-lincosamide-streptogramin B antibiotics. Macrolones are the class of macrolide antibiotics with an outstanding antibacterial profile and reasonable PK parameters resulting in good in vivo efficacy. PMID:27353268

  15. Chemical genetics unveils a key role of mitochondrial dynamics, cytochrome c release and IP3R activity in muscular dystrophy.

    PubMed

    Giacomotto, Jean; Brouilly, Nicolas; Walter, Ludivine; Mariol, Marie-Christine; Berger, Joachim; Ségalat, Laurent; Becker, Thomas S; Currie, Peter D; Gieseler, Kathrin

    2013-11-15

    Duchenne muscular dystrophy (DMD) is a neuromuscular disease caused by mutations in the dystrophin gene. The subcellular mechanisms of DMD remain poorly understood and there is currently no curative treatment available. Using a Caenorhabditis elegans model for DMD as a pharmacologic and genetic tool, we found that cyclosporine A (CsA) reduces muscle degeneration at low dose and acts, at least in part, through a mitochondrial cyclophilin D, CYN-1. We thus hypothesized that CsA acts on mitochondrial permeability modulation through cyclophilin D inhibition. Mitochondrial patterns and dynamics were analyzed, which revealed dramatic mitochondrial fragmentation not only in dystrophic nematodes, but also in a zebrafish model for DMD. This abnormal mitochondrial fragmentation occurs before any obvious sign of degeneration can be detected. Moreover, we demonstrate that blocking/delaying mitochondrial fragmentation by knocking down the fission-promoting gene drp-1 reduces muscle degeneration and improves locomotion abilities of dystrophic nematodes. Further experiments revealed that cytochrome c is involved in muscle degeneration in C. elegans and seems to act, at least in part, through an interaction with the inositol trisphosphate receptor calcium channel, ITR-1. Altogether, our findings reveal that mitochondria play a key role in the early process of muscle degeneration and may be a target of choice for the design of novel therapeutics for DMD. In addition, our results provide the first indication in the nematode that (i) mitochondrial permeability transition can occur and (ii) cytochrome c can act in cell death.

  16. The effects of exogenous hormones on rooting process and the activities of key enzymes of Malus hupehensis stem cuttings.

    PubMed

    Zhang, Wangxiang; Fan, Junjun; Tan, Qianqian; Zhao, Mingming; Zhou, Ting; Cao, Fuliang

    2017-01-01

    Malus hupehensis is an excellent Malus rootstock species, known for its strong adverse-resistance and apomixes. In the present study, stem cuttings of M. hupehensis were treated with three types of exogenous hormones, including indole acetic acid (IAA), naphthalene acetic acid (NAA), or green growth regulator (GGR). The effects and mechanisms of exogenous hormone treatment and antioxidant enzyme activity on adventitious root formation were investigated. The results showed that the apparent morphology of the adventitious root had four stages, including root pre-emergence stage (S0), early stage of root formation (S1), massive root formation stage (S2), and later stage of root formation (S3). The suitable concentrations of the three exogenous hormones, IAA, NAA and GGR, were 100 mg·L-1, 300 mg·L-1, and 300 mg·L-1, respectively. They shortened the rooting time by 25-47.4% and increased the rooting percentages of cuttings by 0.9-1.3 times, compared with that in the control. The dispersion in S0 stage was 3.6 times of that in the S1 stage after exogenous hormone application. The earlier the third critical point (P3) appeared, the shorter the rooting time and the greater the rooting percentage of the cuttings. During rhizogenesis, the activities of three antioxidant enzymes (POD, SOD, and PPO) showed an A-shaped trend. However, peak values of enzyme activity appeared at different points, which were 9 d before the P3, P3, and the fourth critical point (P4), respectively. Exogenous hormone treatment reduced the time to reach the peak value by 18 days, although the peak values of the enzymatic activities did not significantly changed. Our results suggested that exogenous hormone treatment mainly acted during the root pre-emergence stage, accelerated the synthesis of antioxidant enzymes, reduced the rooting time, and consequently promoted root formation. The three kinds of antioxidant enzymes acted on different stages of rooting.

  17. Differential role of reactive oxygen species in the activation of mitogen-activated protein kinases and Akt by key receptors on B-lymphocytes: CD40, the B cell antigen receptor, and CXCR4

    PubMed Central

    Lee, Rosaline L.; Westendorf, Jens

    2007-01-01

    Background Antibodies produced by B-lymphocytes play a key role in the host defense against infection. The development, survival, and activation of B cell is regulated by multiple receptors including the B cell antigen receptor (BCR), which detects the presence of pathogens, CD40, which binds co-stimulatory molecules on activated T cells, and chemokines such as SDF-1 (CXCL12) that play key roles in B cell development and trafficking. Signaling by many receptors results in the generation of reactive oxygen species (ROS) that function as second messengers by regulating the activity of redox-sensitive kinases and phosphatases. We investigated the role of ROS in signaling by the BCR, CD40, and CXCR4, the receptor for SDF-1. We focused on activation of ERK, JNK, p38, and Akt, kinases that regulate multiple processes including cell survival, proliferation, and migration. Results Using the anti-oxidants N-acetyl L-cysteine (NAC) and ebselen to deplete intracellular ROS, we identified a differential requirement for ROS in the activation of ERK, JNK, p38, and Akt by these receptors. We found that CD40 activated JNK, p38, and Akt via redox-dependent pathways that were sensitive to ROS depletion by NAC and ebselen. In contrast, BCR-induced activation of ERK, JNK, p38, and Akt was not affected by ROS depletion. We also found that CXCR4-induced Akt activation was ROS-dependent even though activation of the ERK, JNK, and p38 MAP kinases by CXCR4 occurred via ROS-independent pathways. Conclusion The differential requirement for ROS in the activation of ERK, JNK, p38, and Akt by the BCR, CD40, and CXCR4 likely reflects the multiplicity of upstream activators for each of these kinases, only some of which may be regulated in a redox-dependent manner. These findings support the idea that ROS are important second messengers in B cells and suggest that oxidants or anti-oxidants could be used to modulate B cell activation. PMID:18481208

  18. Long-range Electrostatic Complementarity Governs Substrate Recognition by Human Chymotrypsin C, a Key Regulator of Digestive Enzyme Activation*

    PubMed Central

    Batra, Jyotica; Szabó, András; Caulfield, Thomas R.; Soares, Alexei S.; Sahin-Tóth, Miklós; Radisky, Evette S.

    2013-01-01

    Human chymotrypsin C (CTRC) is a pancreatic serine protease that regulates activation and degradation of trypsinogens and procarboxypeptidases by targeting specific cleavage sites within their zymogen precursors. In cleaving these regulatory sites, which are characterized by multiple flanking acidic residues, CTRC shows substrate specificity that is distinct from that of other isoforms of chymotrypsin and elastase. Here, we report the first crystal structure of active CTRC, determined at 1.9-Å resolution, revealing the structural basis for binding specificity. The structure shows human CTRC bound to the small protein protease inhibitor eglin c, which binds in a substrate-like manner filling the S6-S5′ subsites of the substrate binding cleft. Significant binding affinity derives from burial of preferred hydrophobic residues at the P1, P4, and P2′ positions of CTRC, although acidic P2′ residues can also be accommodated by formation of an interfacial salt bridge. Acidic residues may also be specifically accommodated in the P6 position. The most unique structural feature of CTRC is a ring of intense positive electrostatic surface potential surrounding the primarily hydrophobic substrate binding site. Our results indicate that long-range electrostatic attraction toward substrates of concentrated negative charge governs substrate discrimination, which explains CTRC selectivity in regulating active digestive enzyme levels. PMID:23430245

  19. Dopaminergic D2 receptor is a key player in the substantia nigra pars compacta neuronal activation mediated by REM sleep deprivation.

    PubMed

    Proença, Mariana B; Dombrowski, Patrícia A; Da Cunha, Claudio; Fischer, Luana; Ferraz, Anete C; Lima, Marcelo M S

    2014-01-01

    Currently, several studies addresses the novel link between sleep and dopaminergic neurotransmission, focusing most closely on the mechanisms by which Parkinson's disease (PD) and sleep may be intertwined. Therefore, variations in the activity of afferents during the sleep cycles, either at the level of DA cell bodies in the ventral tegmental area (VTA) and/or substantia nigra pars compacta (SNpc) or at the level of dopamine (DA) terminals in limbic areas may impact functions such as memory. Accordingly, we performed striatal and hippocampal neurochemical quantifications of DA, serotonin (5-HT) and metabolites of rats intraperitoneally treated with haloperidol (1.5 mg/kg) or piribedil (8 mg/kg) and submitted to REM sleep deprivation (REMSD) and sleep rebound (REB). Also, we evaluated the effects of REMSD on motor and cognitive parameters and SNpc c-Fos neuronal immunoreactivity. The results indicated that DA release was strongly enhanced by piribedil in the REMSD group. In opposite, haloperidol prevented that alteration. A c-Fos activation characteristic of REMSD was affected in a synergic manner by piribedil, indicating a strong positive correlation between striatal DA levels and nigral c-Fos activation. Hence, we suggest that memory process is severely impacted by both D2 blockade and REMSD and was even more by its combination. Conversely, the activation of D2 receptor counteracted such memory impairment. Therefore, the present evidence reinforce that the D2 receptor is a key player in the SNpc neuronal activation mediated by REMSD, as a consequence these changes may have direct impact for cognitive and sleep abnormalities found in patients with PD. This article is part of the Special Issue entitled 'The Synaptic Basis of Neurodegenerative Disorders'.

  20. Phenobarbital and propiconazole toxicogenomic profiles in mice show major similarities consistent with the key role that constitutive androstane receptor (CAR) activation plays in their mode of action.

    PubMed

    Currie, Richard A; Peffer, Richard C; Goetz, Amber K; Omiecinski, Curtis J; Goodman, Jay I

    2014-07-03

    Toxicogenomics (TGx) is employed frequently to investigate underlying molecular mechanisms of the compound of interest and, thus, has become an aid to mode of action determination. However, the results and interpretation of a TGx dataset are influenced by the experimental design and methods of analysis employed. This article describes an evaluation and reanalysis, by two independent laboratories, of previously published TGx mouse liver microarray data for a triazole fungicide, propiconazole (PPZ), and the anticonvulsant drug phenobarbital (PB). Propiconazole produced an increase incidence of liver tumors in male CD-1 mice only at a dose that exceeded the maximum tolerated dose (2500 ppm). Firstly, we illustrate how experimental design differences between two in vivo studies with PPZ and PB may impact the comparisons of TGx results. Secondly, we demonstrate that different researchers using different pathway analysis tools can come to different conclusions on specific mechanistic pathways, even when using the same datasets. Finally, despite these differences the results across three different analyses also show a striking degree of similarity observed for PPZ and PB treated livers when the expression data are viewed as major signaling pathways and cell processes affected. Additional studies described here show that the postulated key event of hepatocellular proliferation was observed in CD-1 mice for both PPZ and PB, and that PPZ is also a potent activator of the mouse CAR nuclear receptor. Thus, with regard to the events which are hallmarks of CAR-induced effects that are key events in the mode of action (MOA) of mouse liver carcinogenesis with PB, PPZ-induced tumors can be viewed as being promoted by a similar PB-like CAR-dependent MOA.

  1. National level promotion of physical activity: results from England's ACTIVE for LIFE campaign

    PubMed Central

    Hillsdon, M; Cavill, N; Nanchahal, K; Diamond, A; White, I

    2001-01-01

    STUDY OBJECTIVE—To assess the impact of a national campaign on awareness of the campaign, change in knowledge of physical activity recommendations and self reported physical activity.
DESIGN—three year prospective longitudinal survey using a multi-stage, cluster random probability design to select participants.
SETTING—England.
PARTICIPANTS—A nationally representative sample of 3189 adults aged 16-74 years.
MAIN OUTCOME MEASURES—Awareness of the advertising element of the campaign, changes in knowledge of physical activity recommendations for health and self reported physical activity.
RESULTS—38% of participants were aware of the main advertising images, assessed six to eight months after the main television advertisement. The proportion of participants knowledgeable about moderate physical activity recommendations increased by 3.0% (95% CI: 1.4%, 4.5%) between waves 1 and 2 and 3.7% (95% CI: 2.1%, 5.3%) between waves 1 and 3. The change in proportion of active people between baseline and waves 1 and 2 was
−0.02 (95% CI: −2.0 to +1.7) and between waves 1 and 3 was −9.8 (−7.9 to −11.7).
CONCLUSION—The proportion of participants who were knowledgeable about the new recommendations, increased significantly after the campaign. There was however, no significant difference in knowledge by awareness of the main campaign advertisement. There is no evidence that ACTIVE for LIFE improved physical activity, either overall or in any subgroup.


Keywords: exercise; mass media; follow up studies; health promotion; physical activity PMID:11553661

  2. The effects of exogenous hormones on rooting process and the activities of key enzymes of Malus hupehensis stem cuttings

    PubMed Central

    Tan, Qianqian; Zhao, Mingming; Zhou, Ting; Cao, Fuliang

    2017-01-01

    Malus hupehensis is an excellent Malus rootstock species, known for its strong adverse-resistance and apomixes. In the present study, stem cuttings of M. hupehensis were treated with three types of exogenous hormones, including indole acetic acid (IAA), naphthalene acetic acid (NAA), or green growth regulator (GGR). The effects and mechanisms of exogenous hormone treatment and antioxidant enzyme activity on adventitious root formation were investigated. The results showed that the apparent morphology of the adventitious root had four stages, including root pre-emergence stage (S0), early stage of root formation (S1), massive root formation stage (S2), and later stage of root formation (S3). The suitable concentrations of the three exogenous hormones, IAA, NAA and GGR, were 100 mg·L-1, 300 mg·L-1, and 300 mg·L-1, respectively. They shortened the rooting time by 25–47.4% and increased the rooting percentages of cuttings by 0.9–1.3 times, compared with that in the control. The dispersion in S0 stage was 3.6 times of that in the S1 stage after exogenous hormone application. The earlier the third critical point (P3) appeared, the shorter the rooting time and the greater the rooting percentage of the cuttings. During rhizogenesis, the activities of three antioxidant enzymes (POD, SOD, and PPO) showed an A-shaped trend. However, peak values of enzyme activity appeared at different points, which were 9 d before the P3, P3, and the fourth critical point (P4), respectively. Exogenous hormone treatment reduced the time to reach the peak value by 18 days, although the peak values of the enzymatic activities did not significantly changed. Our results suggested that exogenous hormone treatment mainly acted during the root pre-emergence stage, accelerated the synthesis of antioxidant enzymes, reduced the rooting time, and consequently promoted root formation. The three kinds of antioxidant enzymes acted on different stages of rooting. PMID:28231330

  3. Key Nutrients.

    ERIC Educational Resources Information Center

    Federal Extension Service (USDA), Washington, DC.

    Lessons written to help trainer agents prepare aides for work with families in the Food and Nutrition Program are presented in this booklet. The key nutrients discussed in the 10 lessons are protein, carbohydrates, fat, calcium, iron, iodine, and Vitamins A, B, C, and D. the format of each lesson is as follows: Purpose, Presentation, Application…

  4. EPRRI's Research Activities into the Impact of Key NCLBA Requirements. EPRRI Policy Updates. Issue Three, Fall 2004.

    ERIC Educational Resources Information Center

    Educational Policy Reform Research Institute, 2004

    2004-01-01

    The Educational Policy Reform Research Institute (EPRRI), with funding from the U.S. Department of Education's Office of Special Education Programs, investigates the impact of educational accountability reforms on students with disabilities and on special education. EPRRI addresses the research needs of policymakers and other key stakeholders by…

  5. Polarization: A Key Difference between Man-made and Natural Electromagnetic Fields, in regard to Biological Activity

    PubMed Central

    Panagopoulos, Dimitris J.; Johansson, Olle; Carlo, George L.

    2015-01-01

    In the present study we analyze the role of polarization in the biological activity of Electromagnetic Fields (EMFs)/Electromagnetic Radiation (EMR). All types of man-made EMFs/EMR - in contrast to natural EMFs/EMR - are polarized. Polarized EMFs/EMR can have increased biological activity, due to: 1) Ability to produce constructive interference effects and amplify their intensities at many locations. 2) Ability to force all charged/polar molecules and especially free ions within and around all living cells to oscillate on parallel planes and in phase with the applied polarized field. Such ionic forced-oscillations exert additive electrostatic forces on the sensors of cell membrane electro-sensitive ion channels, resulting in their irregular gating and consequent disruption of the cell’s electrochemical balance. These features render man-made EMFs/EMR more bioactive than natural non-ionizing EMFs/EMR. This explains the increasing number of biological effects discovered during the past few decades to be induced by man-made EMFs, in contrast to natural EMFs in the terrestrial environment which have always been present throughout evolution, although human exposure to the latter ones is normally of significantly higher intensities/energy and longer durations. Thus, polarization seems to be a trigger that significantly increases the probability for the initiation of biological/health effects. PMID:26456585

  6. Polarization: A Key Difference between Man-made and Natural Electromagnetic Fields, in regard to Biological Activity.

    PubMed

    Panagopoulos, Dimitris J; Johansson, Olle; Carlo, George L

    2015-10-12

    In the present study we analyze the role of polarization in the biological activity of Electromagnetic Fields (EMFs)/Electromagnetic Radiation (EMR). All types of man-made EMFs/EMR - in contrast to natural EMFs/EMR - are polarized. Polarized EMFs/EMR can have increased biological activity, due to: 1) Ability to produce constructive interference effects and amplify their intensities at many locations. 2) Ability to force all charged/polar molecules and especially free ions within and around all living cells to oscillate on parallel planes and in phase with the applied polarized field. Such ionic forced-oscillations exert additive electrostatic forces on the sensors of cell membrane electro-sensitive ion channels, resulting in their irregular gating and consequent disruption of the cell's electrochemical balance. These features render man-made EMFs/EMR more bioactive than natural non-ionizing EMFs/EMR. This explains the increasing number of biological effects discovered during the past few decades to be induced by man-made EMFs, in contrast to natural EMFs in the terrestrial environment which have always been present throughout evolution, although human exposure to the latter ones is normally of significantly higher intensities/energy and longer durations. Thus, polarization seems to be a trigger that significantly increases the probability for the initiation of biological/health effects.

  7. Quantum Key Distribution

    NASA Astrophysics Data System (ADS)

    Hughes, Richard

    2004-05-01

    Quantum key distribution (QKD) uses single-photon communications to generate the shared, secret random number sequences that are used to encrypt and decrypt secret communications. The unconditional security of QKD is based on the interplay between fundamental principles of quantum physics and information theory. An adversary can neither successfully tap the transmissions, nor evade detection (eavesdropping raises the key error rate above a threshold value). QKD could be particularly attractive for free-space optical communications, both ground-based and for satellites. I will describe a QKD experiment performed over multi-kilometer line-of-sight paths, which serves as a model for a satellite-to-ground key distribution system. The system uses single-photon polarization states, without active polarization switching, and for the first time implements the complete BB84 QKD protocol including, reconciliation, privacy amplification and the all-important authentication stage. It is capable of continuous operation throughout the day and night, achieving the self-sustaining production of error-free, shared, secret bits. I will also report on the results of satellite-to-ground QKD modeling.

  8. Targeted Ablation, Silencing, and Activation Establish Glycinergic Dorsal Horn Neurons as Key Components of a Spinal Gate for Pain and Itch

    PubMed Central

    Foster, Edmund; Wildner, Hendrik; Tudeau, Laetitia; Haueter, Sabine; Ralvenius, William T.; Jegen, Monika; Johannssen, Helge; Hösli, Ladina; Haenraets, Karen; Ghanem, Alexander; Conzelmann, Karl-Klaus; Bösl, Michael; Zeilhofer, Hanns Ulrich

    2015-01-01

    Summary The gate control theory of pain proposes that inhibitory neurons of the spinal dorsal horn exert critical control over the relay of nociceptive signals to higher brain areas. Here we investigated how the glycinergic subpopulation of these neurons contributes to modality-specific pain and itch processing. We generated a GlyT2::Cre transgenic mouse line suitable for virus-mediated retrograde tracing studies and for spatially precise ablation, silencing, and activation of glycinergic neurons. We found that these neurons receive sensory input mainly from myelinated primary sensory neurons and that their local toxin-mediated ablation or silencing induces localized mechanical, heat, and cold hyperalgesia; spontaneous flinching behavior; and excessive licking and biting directed toward the corresponding skin territory. Conversely, local pharmacogenetic activation of the same neurons alleviated neuropathic hyperalgesia and chloroquine- and histamine-induced itch. These results establish glycinergic neurons of the spinal dorsal horn as key elements of an inhibitory pain and itch control circuit. PMID:25789756

  9. The emotional importance of key: do Beatles songs written in different keys convey different emotional tones?

    PubMed

    Whissel, R; Whissel, C

    2000-12-01

    Lyrics from 155 songs written by the Lennon-McCartney team were scored using the Dictionary of Affect in Language. Resultant scores (pleasantness, activation, and imagery of words) were compared across key signatures using one way analyses of variance. Words from songs written in minor keys were less pleasant and less active than those from songs written in major keys. Words from songs written in the key of F scored extremely low on all three measures. Lyrics from the keys of C, D, and G were relatively active in tone. Results from Dictionary scoring were compared with assignments of character to keys made more than one century ago and with current musicians' opinions.

  10. Overview of JT-60U results towards the resolution of key physics and engineering issues in ITER and JT-60SA

    NASA Astrophysics Data System (ADS)

    Isayama, A.; JT-60 Team

    2011-09-01

    This paper presents an overview of recent results from JT-60U. Topics we particularly focus on are (1) the mechanism determining the rotation profile and the effect of rotation on/from transport and stability, (2) the edge localized mode (ELM) physics and active ELM control and (3) plasma-wall interactions. An analysis of the momentum transport showed that rotation with a high pressure gradient can be reproduced by introducing a residual stress term proportional to the momentum diffusivity and the pressure gradient. Also, the momentum diffusivity in an internal transport barrier (ITB) region was reduced to an order similar to that of the ion thermal diffusivity. A comparison of the edge pedestal characteristics between JT-60U and JET with matched shape and operational parameters showed that the edge pressure did not change with increasing toroidal field (TF) ripple up to 1%, whereas a linear shift of the rotation velocity to the counter-direction was observed with increasing TF ripple. The absolute evaluation of tungsten accumulation in the core plasma by a spectroscopic method clarified that tungsten accumulation increased with increasing toroidal rotation in the counter-direction while an H-mode was sustained even at a tungsten density of 10-3 times the electron density. Active control of neoclassical tearing mode (NTM) islands by the electron cyclotron current drive showed that the growth of NTM islands decelerated the plasma rotation. A transition to a low-rotation frequency state occurred for larger NTM islands. A statistical analysis of the precursor of type I ELM showed a small growth rate of γ/ωA ~ 10-3 (where γ and ωA are the growth rate and Alfvén angular frequency, respectively). The measurement of the precursor at different toroidal locations showed that the toroidal mode number was 8-10 or 14-16. Energetic-particle-driven wall modes (EWMs) were found to trigger ELMs and decrease the ELM amplitude to half of that without EWMs. Enhancement of the

  11. Balloon-related activities of the IMK/FZK: instruments, activities and results

    NASA Astrophysics Data System (ADS)

    Friedl-Vallon, Felix; Oelhaf, Hermann; Kleinert, Anne; Lengel, Anton; Maucher, Guido; Nordmeyer, Hans; Stowasser, Markus; Wetzel, Gerald; Fischer, Herbert

    2001-08-01

    The Institut für Meteorologie und Klimaforschung of the Forschungszentrum Karlsruhe (IMK/FZK) is operating a balloon-borne instrument for atmospheric research since the late eighties. The MIPAS-B (Michelson Interferometer for Passive Atmospheric Sounding - Balloon) instrument, a cryogenic Fourier spectrometer for limb emission measurements has flown 13 times in two different versions from France and Sweden. In this time the instrument has participated in three large international campaigns (EASOE, SESAME, THESEO) and several smaller field-activities (CHORUS, CHELOSBA, POSTA) concerning stratospheric chemistry from which important contributions to the understanding of the Arctic ozone depletion mechanisms have been achieved. Additionally, the instrument participated as core payload in the validation of the Japanese ILAS instrument on-board ADEOS and supported the validation of the American CLAES instrument onboard UARS. MIPAS-B data served also to test the level 2 algorithms for the MIPAS-instrument on-board ENVISAT. Present activities focus on the understanding of the composition and role of polar stratospheric clouds. The second centre of attention in the next years will be the validation of the European satellite sensors GOMOS, MIPAS, and SCIAMACHY with the established MIPAS-B version.

  12. CCN Activity, Hygroscopicity, and Droplet Activation Kinetics of Secondary Organic Aerosol Resulting from the 2010 Gulf Oil Spill

    NASA Astrophysics Data System (ADS)

    Moore, R.; Lathem, T. L.; Cerully, K.; Bahreini, R.; Brock, C. A.; Langridge, J. M.; Middlebrook, A. M.; Nenes, A.; Calnex Science Team

    2010-12-01

    We present an analysis of the hygroscopicity and droplet activation kinetics of cloud condensation nuclei (CCN) sampled onboard the National Oceanic and Atmospheric Administration WP-3D aircraft downwind of the Deepwater Horizon oil spill site on June 8th and 10th, 2010. This set of measurements provides a unique case study for assessing in-situ the impact of fresh, hydrocarbonlike aerosols, which are expected to be formed via gas-to-particle conversion of the semi-volatile vapors released from oil evaporation. Similar hydrocarbon-rich aerosols constitute an important local emissions source in urban areas, but often coexist as an external/partially-internal mixture with more-oxidized, aged organic and sulfate aerosol. The DWH site provides the means to study the hygroscopic properties of these less-oxidized organic aerosols above a cleaner environmental background typical of marine environments in order to better discern their contribution to CCN activity and droplet growth. Measurements were performed with a Droplet Measurement Technologies Streamwise, Thermal-Gradient CCN counter, operating both as a counter (s=0.3%) and as a spectrometer (s=0.2-0.6%) using the newly-developed Scanning Flow CCN Analysis (SFCA) technique [1]. The instrument measures both the number concentration of particles able to nucleate droplets and also their resulting droplet sizes. The measured size information combined with a comprehensive computational fluid dynamics instrument model enables us to determine the rate of water uptake onto the particles and parameterize it in terms of an effective mass transfer coefficient [2], a key parameter needed to predict the number of activated droplets in ambient clouds. Non-refractory aerosol chemical composition was measured with an Aerodyne compact time-of-flight aerosol mass spectrometer. It was observed that the aerosols sampled downwind of the site on both days were composed predominantly of organics with a low degree of oxidation and low

  13. [Change in the activity of the key gluconeogenesis enzymes in the rat liver and kidneys during the action of subextreme and extreme factors on the body].

    PubMed

    Panin, L E; Kolosova, I E; Nechaev, Iu S

    1979-06-01

    The activity of glucogenesis key enzymes (phosphoenolpyruvate carboxinase, fructoso-1,6-siphosphatase, glucoso-6-phosphatase) of the rat liver and kidneys was studied simultaneously under the effect of extreme and subextreme factors on the organism. The low initial phosphoenolpyruvate carboxikinase activity in the liver and its high inductivity under extreme conditions suggest a role of this enzyme as limiting link in glyconeogenesis. The activity of phosphoenolpyruvate carboxinase in the kidneys is comparable to that of fructoso-1,6-diphosphatase; it is considerably higher than the activity of glucoso-6-phosphatase. The phosphoenolpyruvate carboxinase activity in the kidneys is 5--6 times higher than in the liver. The activity of phosphoenolpyruvate carboxinase and glucoso-6-phosphatase is increased under the effect of extreme factors, and that of fructoso-1,6-diphosphatase remains unchanged. The lack of clear synchronous changes in the activity of glucogenesis key enzymes in the liver and kidneys indicates that the cells of these organs do not provide the united operon for phosphoenolpyruvate carboxinase, fructoso-1,6-diphosphatase and glucoso-6-phosphatase with common regulation mechanism.

  14. The Nisi Fault as a key structure for understanding the active deformation of the NW Peloponnese, Greece

    NASA Astrophysics Data System (ADS)

    Zygouri, V.; Koukouvelas, I. K.; Kokkalas, S.; Xypolias, P.; Papadopoulos, G. A.

    2015-05-01

    The previously unknown Nisi Fault in NW Peloponnese was ruptured during the 2008 Movri Mountain earthquake attaining a maximum offset of 25 cm. The fault is interpreted as a branch of a flower structure above a blind strike-slip fault. We investigate the Nisi Fault seismotectonic evolution using morphotectonic analysis in order to determine whether the landscape is affected by tectonic forcing and paleoseismology to determine earthquake recurrence interval and fault slip rates. We applied several geomorphic indices, such as the asymmetry factor (AF), the stream length-gradient index (SL), the valley floor width to valley height ratio (Vf), the mountain-front sinuosity (Smf), the drainage basin shape (Bs) and the hypsometric curve (Hc), in four large drainage basins of the study area. The results show that fault-related vertical motions and the associated tilting influenced the drainage geometry and the landscape development. Values of stream-gradient indices (SL) are relatively high close to the fault trace. Mountain-front sinuosity (Smf) mean values along the fault zones range from 1.12 to 1.23. Valley floor width to valley height ratios (Vf) mean values along the studied fault range between 0.21 and 2.50. Drainage basin shape (BS) mean values along the fault range from 1.04 to 3.72. Lateral fault growth was likely achieved by propagation primarily towards north-northwestward. The paleoseismic history of the fault, investigated by a trench and 14C dating of seven samples, indicates two morphogenic earthquakes in the last 1 kyr. Therefore, we suggest that the Nisi Fault displays a slip rate on the order of 1 mm/yr and a recurrence interval ranging between 300 and 600 years. From a seismotectonic point of view, the fault is classified as high activity rate, with abundant but discontinuous geomorphic evidence of its activity. Other similar faults affecting the western Peloponnese can be envisaged with a similar procedure. Additionally, the seismic history and surface

  15. The crystal structure of necrosis- and ethylene-inducing protein 2 from the causal agent of cacao's Witches' Broom disease reveals key elements for its activity.

    PubMed

    Zaparoli, Gustavo; Barsottini, Mario Ramos de Oliveira; de Oliveira, Juliana Ferreira; Dyszy, Fabio; Teixeira, Paulo José Pereira Lima; Barau, Joan Grande; Garcia, Odalys; Costa-Filho, Antonio José; Ambrosio, Andre Luis Berteli; Pereira, Gonçalo Amarante Guimarães; Dias, Sandra Martha Gomes

    2011-11-15

    The necrosis- and ethylene-inducing peptide 1 (NEP1)-like proteins (NLPs) are proteins secreted from bacteria, fungi and oomycetes, triggering immune responses and cell death in dicotyledonous plants. Genomic-scale studies of Moniliophthora perniciosa, the fungus that causes the Witches' Broom disease in cacao, which is a serious economic concern for South and Central American crops, have identified five members of this family (termed MpNEP1-5). Here, we show by RNA-seq that MpNEP2 is virtually the only NLP expressed during the fungus infection. The quantitative real-time polymerase chain reaction results revealed that MpNEP2 has an expression pattern that positively correlates with the necrotic symptoms, with MpNEP2 reaching its highest level of expression at the advanced necrotic stage. To improve our understanding of MpNEP2's molecular mechanism of action, we determined the crystallographic structure of MpNEP2 at 1.8 Å resolution, unveiling some key structural features. The implications of a cation coordination found in the crystal structure were explored, and we show that MpNEP2, in contrast to another previously described member of the NLP family, NLP(Pya) from Pythium aphanidermatum, does not depend on an ion to accomplish its necrosis- and electrolyte leakage-promoting activities. Results of site-directed mutagenesis experiments confirmed the importance of a negatively charged cavity and an unforeseen hydrophobic β-hairpin loop for MpNEP2 activity, thus offering a platform for compound design with implications for disease control. Electron paramagnetic resonance and fluorescence assays with MpNEP2 performed in the presence of lipid vesicles of different compositions showed no sign of interaction between the protein and the lipids, implying that MpNEP2 likely requires other anchoring elements from the membrane to promote cytolysis or send death signals.

  16. Understanding central carbon metabolism of rapidly proliferating mammalian cells based on analysis of key enzymatic activities in GS-CHO cell lines.

    PubMed

    Zou, Wu; Al-Rubeai, Mohamed

    2016-09-01

    The central carbon metabolism (glycolysis, the pentose phosphate pathway [PPP], and the tricarboxylic acid [TCA] cycle) plays an essential role in the supply of biosynthetic precursors and energy. How the central carbon metabolism changes with the varying growth rates in the in vitro cultivation of rapidly proliferating mammalian cells, such as cancer cells and continuous cell lines for recombinant protein production, remains elusive. Based on relationships between the growth rate and the activity of seven key enzymes from six cell clones, this work reports finding an important metabolic characteristic in rapidly proliferating glutamine synthetase-Chinese hamster ovary cells. The key enzymatic activity involved in the TCA cycle that is responsible for the supply of energy became elevated as the growth rate exhibited increases, while the activity of key enzymes in metabolic pathways (glycolysis and the PPP), responsible for the supply of biosynthetic precursors, tended to decrease-suggesting that rapidly proliferating cells still depended predominantly on the TCA cycle rather than on aerobic glycolysis for their energetic demands. Meanwhile, the growth-limiting resource was most likely biosynthetic substrates rather than energy provision. In addition, the multifaceted role of glucose-6-phosphate isomerase (PGI) was confirmed, based on a significant correlation between PGI activity and the percentage of G2/M-phase cells.

  17. Results of a workshop concerning impacts of various activities on the functions of bottomland hardwoods

    USGS Publications Warehouse

    Roelle, James E.; Auble, Gregor T.; Hamilton, David B.; Horak, Gerald C.; Johnson, Richard L.; Segelquist, Charles A.

    1987-01-01

    Under Section 404 of the Clean Water Act, the U.S. Environmental Protection Agency (EPA) has regulatory responsibilities related to the discharge of dredged or fill material into the Nation’s waters. In addition to its advisory role in the U.S. Army Corps of Engineers' permit program, EPA has a number of specific authorities, including formulation of the Section 404(b)(1) guidelines, use of Section 404(c) to prohibit disposal at particular sites, and enforcement actions for unauthorized discharges. A number of recent court cases focus on the geographic scope of Section 404 jurisdiction in potential bottomland hardwood (BLH) wetlands and the nature of landclearing activities in these areas that require a permit under Section 404. Accordingly, EPA needs to establish the scientific basis for implementing its responsibilities under Section 404 in bottomland hardwoods. EPA is approaching this task through a series of workshops designed to provide current scientific information on bottomland hardwoods and to organize that information in a manner pertinent to key policy questions. The first two workshops in the series were originally conceived as technically oriented meetings that would provide the information necessary to develop policy options at the third workshop. More specifically, the first workshop was designed to examine a zonation concept as a means of characterizing different BLH communities and describing variations in their functions along a soil moisture gradient. The second workshop was perceived as an attempt to evaluate the impacts of various activities on those functions. However, one conclusion of the first workshop, which was held in December 1984 in St. Francisville, Louisiana, was that the zonation approach does not describe the variability in the functions performed by BLH ecosystems sufficiently well to allow its use as the sole basis for developing a regulatory framework. That is, factors other than zone were considered critical for an effective

  18. 76 FR 67142 - Certain Activated Carbon From the People's Republic of China: Final Results and Partial...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-10-31

    ...-activation chemical treatment (chemical or water washing, chemical impregnation or other treatment), or... dehydrates molecules in the raw material, and results in the formation of water that is removed from the raw... analysis memoranda. \\13\\ CCT submitted Active Carbon India Private Limited's (``Active Carbon'')...

  19. Structural Descriptors of Zeolitic-Imidazolate Frameworks Are Keys to the Activity of Fe-N-C Catalysts.

    PubMed

    Armel, Vanessa; Hindocha, Sheena; Salles, Fabrice; Bennett, Stephen; Jones, Deborah; Jaouen, Frédéric

    2017-01-11

    Active and inexpensive catalysts for oxygen reduction are crucially needed for the widespread development of polymer electrolyte fuel cells and metal-air batteries. While iron-nitrogen-carbon materials pyrolytically prepared from ZIF-8, a specific zeolitic imidazolate framework (ZIF) with sodalite topology, have shown enhanced activities toward oxygen reduction in acidic electrolyte, the rational design of sacrificial metal-organic frameworks toward this application has hitherto remained elusive. Here, we report for the first time that the oxygen reduction activity of Fe-N-C catalysts positively correlates with the cavity size and mass-specific pore volume in pristine ZIFs. The high activity of Fe-N-C materials prepared from ZIF-8 could be rationalized, and another ZIF structure leading to even higher activity was identified. In contrast, the ORR activity is mostly unaffected by the ligand chemistry in pristine ZIFs. These structure-property relationships will help identifying novel sacrificial ZIF or porous metal-organic frameworks leading to even more active Fe-N-C catalysts. The findings are of great interest for a broader application of the class of inexpensive metal-nitrogen-carbon catalysts that have shown promising activity also for the hydrogen evolution (Co-N-C) and carbon dioxide reduction (Fe-N-C and Mn-N-C).

  20. Fhl2 deficiency results in osteopenia due to decreased activity of osteoblasts

    PubMed Central

    Günther, Thomas; Poli, Cecilia; Müller, Judith M; Catala-Lehnen, Philip; Schinke, Thorsten; Yin, Na; Vomstein, Sandra; Amling, Michael; Schüle, Roland

    2005-01-01

    Osteoporosis is one of the major health problems today, yet little is known about the loss of bone mass caused by reduced activity of the bone-forming osteoblasts. Here we show that mice deficient for the transcriptional cofactor four and a half LIM domains 2 (Fhl2) exhibit a dramatic decrease of bone mass in both genders. Osteopenia is caused by a reduced bone formation rate that is solely due to the diminished activity of Fhl2-deficient osteoblasts, while their number remains unchanged. The number and activity of the bone-resorbing cells, the osteoclasts, is not altered. Enforced expression of Fhl2 in differentiated osteoblasts boosts mineralization in cell culture and, importantly, enhances bone formation in transgenic animals. Fhl2 increases the transcriptional activity of runt-related transcription factor 2 (Runx2), a key regulator of osteoblast function, and both proteins interact in vitro and in vivo. In summary, we present Fhl2-deficient mice as a unique model for osteopenia due to decreased osteoblast activity. Our data offer a novel concept to fight osteoporosis by modulating the anabolic activity of osteoblasts via Fhl2. PMID:16079911

  1. Histochemical location of key enzyme activities involved in receptivity and self-incompatibility in the olive tree (Olea europaea L.).

    PubMed

    Serrano, Irene; Olmedilla, Adela

    2012-12-01

    Stigma-surface and style enzymes are important for pollen reception, selection and germination. This report deals with the histochemical location of the activity of four basic types of enzyme involved in these processes in the olive (Olea europaea L.). The detection of peroxidase, esterase and acid-phosphatase activities at the surface of the stigma provided evidence of early receptivity in olive pistils. The stigma maintained its receptivity until the arrival of pollen. Acid-phosphatase activity appeared in the style at the moment of anthesis and continued until the fertilization of the ovule. RNase activity was detected in the extracellular matrix of the styles of flowers just before pollination and became especially evident in pistils after self-pollination. This activity gradually decreased until it practically disappeared in more advanced stages. RNase activity was also detected in pollen tubes growing in pollinated pistils and appeared after in vitro germination in the presence of self-incompatible pistils. These findings suggest that RNases may well be involved in intraspecific pollen rejection in olive flowers. To the best of our knowledge this is the first time that evidence of enzyme activity in stigma receptivity and pollen selection has been described in this species.

  2. KEY COMPARISON: Comparisons CCRI(II)-K3.F-18 and APMP.RI(II)-K3.F-18 of activity measurements of the radionuclide 18F and links to the key comparison reference value of the BIPM.RI(II)-K1.F-18 comparison

    NASA Astrophysics Data System (ADS)

    Ratel, G.; Michotte, C.; Woods, M. J.

    2005-01-01

    In 2003, the CCRI(II) decided that an indirect comparison of 18F measurements piloted by the National Physical Laboratory (NPL), UK in 2001 was sufficiently well constructed that it could be converted into a CCRI(II) comparison, with comparison identifier CCRI(II)-K3.F-18. At the same time, the pilot laboratory made a bilateral comparison with the institute in Chinese Taipei, comparison identifier APMP.RI(II)-K3.F-18. The results of the comparisons have been reported and the key comparison working group (KCWG) of the CCRI(II) has approved the mechanism to link all the results to the key comparison reference value (KCRV) of 18F. The KCRV has been determined through the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures (BIPM), with comparison identifier BIPM.RI(II)-K1.F-18. These comparisons have enabled a further four results to be added to the matrix of degrees of equivalence for 18F activity measurements. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by Section II of the Consultative Committee for Ionizing Radiation (CCRI(II)), according to the provisions of the Mutual Recognition Arrangement (MRA).

  3. Effect of Ethanol Accumulation on Porcine Interferon-α Production by Pichia pastoris and Activities of Key Enzymes in Carbon Metabolism.

    PubMed

    Ding, Jian; Gao, Minjie; Hou, Guoli; Liang, Kexue

    2015-08-01

    In production of porcine interferon α (pIFN-α) by Pichia pastoris, improper glycerol feeding strategy leads to ethanol accumulation in the last stage of growth phase. In the present study, taking two runs with low ethanol accumulation under 2 g/L as control group, effects of long-term (>4 h) and instantaneous high ethanol concentration (>10 g/L) on pIFN-α production, and activities of key enzymes in carbon metabolism were discussed. As a result, compared with control group, pIFN-α expression level was decreased about 4~12 folds under long-term high ethanol concentration, from the level above 3 g/L to the level under 1 g/L; pIFN-α expression level was decreased about 8 folds under instantaneous high ethanol concentration, reaching to the low level of 0.42 g/L. The low production of pIFN-α was caused by the severe inhibitory effect of ethanol on these enzymes.

  4. MicroRNA-29 fine-tunes the expression of key FOXA2-activated lipid metabolism genes and is dysregulated in animal models of insulin resistance and diabetes.

    PubMed

    Kurtz, C Lisa; Peck, Bailey C E; Fannin, Emily E; Beysen, Carine; Miao, Ji; Landstreet, Stuart R; Ding, Shengli; Turaga, Vandana; Lund, P Kay; Turner, Scott; Biddinger, Sudha B; Vickers, Kasey C; Sethupathy, Praveen

    2014-09-01

    MicroRNAs (miRNAs) have emerged as biomarkers of metabolic status, etiological factors in complex disease, and promising drug targets. Recent reports suggest that miRNAs are critical regulators of pathways underlying the pathophysiology of type 2 diabetes. In this study, we demonstrate by deep sequencing and real-time quantitative PCR that hepatic levels of Foxa2 mRNA and miR-29 are elevated in a mouse model of diet-induced insulin resistance. We also show that Foxa2 and miR-29 are significantly upregulated in the livers of Zucker diabetic fatty (fa/fa) rats and that the levels of both returned to normal upon treatment with the insulin-sensitizing agent pioglitazone. We present evidence that miR-29 expression in human hepatoma cells is controlled in part by FOXA2, which is known to play a critical role in hepatic energy homeostasis. Moreover, we demonstrate that miR-29 fine-tunes FOXA2-mediated activation of key lipid metabolism genes, including PPARGC1A, HMGCS2, and ABHD5. These results suggest that miR-29 is an important regulatory factor in normal metabolism and may represent a novel therapeutic target in type 2 diabetes and related metabolic syndromes.

  5. Sets, Subsets, and Dichotomous Keys

    ERIC Educational Resources Information Center

    Cole, E. James

    1973-01-01

    Discusses the procedures that should be observed in constructing a dichotomous key. The keying exercise described was used as a laboratory activity in a biology course for elementary education majors, however it could be used in other courses. (JR)

  6. Biochemical and toxicological evaluation of nano-heparins in cell functional properties, proteasome activation and expression of key matrix molecules.

    PubMed

    Piperigkou, Zoi; Karamanou, Konstantina; Afratis, Nikolaos A; Bouris, Panagiotis; Gialeli, Chrysostomi; Belmiro, Celso L R; Pavão, Mauro S G; Vynios, Dimitrios H; Tsatsakis, Aristidis M

    2016-01-05

    The glycosaminoglycan heparin and its derivatives act strongly on blood coagulation, controlling the activity of serine protease inhibitors in plasma. Nonetheless, there is accumulating evidence highlighting different anticancer activities of these molecules in numerous types of cancer. Nano-heparins may have great biological significance since they can inhibit cell proliferation and invasion as well as inhibiting proteasome activation. Moreover, they can cause alterations in the expression of major modulators of the tumor microenvironment, regulating cancer cell behavior. In the present study, we evaluated the effects of two nano-heparin formulations: one isolated from porcine intestine and the other from the sea squirt Styela plicata, on a breast cancer cell model. We determined whether these nano-heparins are able to affect cell proliferation, apoptosis and invasion, as well as proteasome activity and the expression of extracellular matrix molecules. Specifically, we observed that nano-Styela compared to nano-Mammalian analogue has higher inhibitory role on cell proliferation, invasion and proteasome activity. Moreover, nano-Styela regulates cell apoptosis, expression of inflammatory molecules, such as IL-6 and IL-8 and reduces the expression levels of extracellular matrix macromolecules, such as the proteolytic enzymes MT1-MMP, uPA and the cell surface proteoglycans syndecan-1 and -2, but not on syndecan-4. The observations reported in the present article indicate that nano-heparins and especially ascidian heparin are effective agents for heparin-induced effects in critical cancer cell functions, providing an important possibility in pharmacological targeting.

  7. Key role of the loop connecting the two beta strands of mussel defensin in its antimicrobial activity.

    PubMed

    Romestand, Bernard; Molina, Franck; Richard, Véronique; Roch, Philippe; Granier, Claude

    2003-07-01

    To elucidate the structural features of the mussel defensin MGD1 required for antimicrobial activity, we synthesized a series of peptides corresponding to the main known secondary structures of the molecule and evaluated their activity towards Gram-positive and Gram-negative bacteria, and filamentous fungi. We found that the nonapeptide corresponding to residues 25-33 of MGD1 (CGGWHRLRC) exhibited bacteriostatic activity once it was cyclized by a non-naturally occurring disulfide bridge. Longer peptides corresponding to the amino acid sequences of the alpha-helical part or to the beta-strands of MGD1 had no detectable activity. The bacteriostatic activity of the sequence 25-33 was strictly dependent on the bridging of Cys25 and Cys33 and was proportional to the theoretical isoelectric point of the peptide, as deduced from the variation of activity in a set of peptide analogues of the 25-33 sequence with different numbers of cationic charges. By using confocal fluorescence microscopy, we found that the cyclic peptides bound to Gram-positive bacteria without apparent lysis. However, by using a fluorescent dye, we observed that dead bacteria had been permeated by the cyclic peptide 25-33. Sequence comparisons in the family of arthopod defensins indicate that MGD1 belongs to a subfamily of the insect defensins, characterized by the constant occurrence of both positively charged and hydrophobic amino acids in the loop. Modelling studies showed that in the MGD1 structure, positively charged and hydrophobic residues are organized in two layered clusters, which might have a functional significance in the docking of MGD1 to the bacterial membrane.

  8. Direct Synthesis of Protoberberine Alkaloids by Rh-Catalyzed C-H Bond Activation as the Key Step.

    PubMed

    Jayakumar, Jayachandran; Cheng, Chien-Hong

    2016-01-26

    A one-pot reaction of substituted benzaldehydes with alkyne-amines by a Rh-catalyzed C-H activation and annulation to afford various natural and unnatural protoberberine alkaloids is reported. This reaction provides a convenient route for the generation of a compound library of protoberberine salts, which recently have attracted great attention because of their diverse biological activities. In addition, pyridinium salt derivatives can also be formed in good yields from α,β-unsaturated aldehydes and amino-alkynes. This reaction proceeds with excellent regioselectivity and good functional group compatibility under mild reaction conditions by using O2 as the oxidant.

  9. Testing Models: A Key Aspect to Promote Teaching Activities Related to Models and Modelling in Biology Lessons?

    ERIC Educational Resources Information Center

    Krell, Moritz; Krüger, Dirk

    2016-01-01

    This study investigated biology teachers' (N = 148) understanding of models and modelling (MoMo), their model-related teaching activities and relations between the two. A framework which distinguishes five aspects of MoMo in science ("nature of models," "multiple models," "purpose of models," "testing…

  10. The Online Interactive Curriculum Portal as One Key to the Well-Structured Learning Activity of Students.

    ERIC Educational Resources Information Center

    Lehtonen, Miika

    In contrast to traditional types of learning and teaching processes and learning media, such as printed material for Web and hypermedia learning resources, Web resources and Web-based activities are quite often unfortunately more or less separate parts of the planning process and curriculum documentation in an organization's traditional…

  11. Motivational Activities for High School Economics, Keyed to the New York State Syllabus "Economics and Economic Decision Making."

    ERIC Educational Resources Information Center

    Dawson, George G.

    This manual provides secondary school teachers with ideas for relating economics to student needs, interests, and experiences. The tentative syllabus "Economics and Economic Decision Making," designed for 12th grade social studies by the New York State Education Department in 1987, is used as a guide. Motivational activities for the 18…

  12. [Insulin-like growth factor 1 and the key markers of proteolysis during the acute period of readaptation of the muscle atrophied as a result of unloading].

    PubMed

    Kachaeva, E V; Turtikova, O V; Leĭnsoo, T A; Shenkman, B S

    2010-01-01

    It has been shown that, after prolonged disuse, the accumulation of muscle mass and the recovery of soleus fibers volume are caused by water accumulation rather than protein synthesis intensification. At the same time, expression rate of the main markers of the activity of ubiquitin-proteasome system remained increased on the 3rd day of reloading and decreased to the control by the 7th day. Both the quantity of the insulin-like growth factor 1 and the number of satellite cells fused with muscle fibers and of myonuclei began to increase only on the 7th day of reloading. The data obtained evidenced a significant inertness of the postural muscle during its adaptation to the load (normal gravity) after prolonged disuse.

  13. Plastid Localization of the Key Carotenoid Enzyme Phytoene Synthase Is Altered by Isozyme, Allelic Variation, and Activity[W

    PubMed Central

    Shumskaya, Maria; Bradbury, Louis M.T.; Monaco, Regina R.; Wurtzel, Eleanore T.

    2012-01-01

    Plant carotenoids have unique physiological roles related to specific plastid suborganellar locations. Carotenoid metabolic engineering could enhance plant adaptation to climate change and improve food security and nutritional value. However, lack of fundamental knowledge on carotenoid pathway localization limits targeted engineering. Phytoene synthase (PSY), a major rate-controlling carotenoid enzyme, is represented by multiple isozymes residing at unknown plastid sites. In maize (Zea mays), the three isozymes were transiently expressed and found either in plastoglobuli or in stroma and thylakoid membranes. PSY1, with one to two residue modifications of naturally occurring functional variants, exhibited altered localization, associated with distorted plastid shape and formation of a fibril phenotype. Mutating the active site of the enzyme reversed this phenotype. Discovery of differential PSY locations, linked with activity and isozyme type, advances the engineering potential for modifying carotenoid biosynthesis. PMID:23023170

  14. The relative protein abundance of UGT1A alternative splice variants as a key determinant of glucuronidation activity in vitro.

    PubMed

    Rouleau, Mélanie; Roberge, Joannie; Falardeau, Sarah-Ann; Villeneuve, Lyne; Guillemette, Chantal

    2013-04-01

    Alternative splicing (AS) is one of the most significant components of the functional complexity of human UDP-glucuronosyltransferase enzymes (UGTs), particularly for the UGT1A gene, which represents one of the best examples of a drug-metabolizing gene regulated by AS. Shorter UGT1A isoforms [isoform 2 (i2)] are deficient in glucuronic acid transferase activity but function as negative regulators of enzyme activity through protein-protein interaction. Their abundance, relative to active UGT1A enzymes, is expected to be a determinant of the global transferase activity of cells and tissues. Here we tested whether i2-mediated inhibition increases with greater abundance of the i2 protein relative to the isoform 1 (i1) enzyme, using the extrahepatic UGT1A7 as a model and a series of 23 human embryonic kidney 293 clonal cell lines expressing variable contents of i1 and i2 proteins. Upon normalization for i1, a significant reduction of 7-ethyl-10-hydroxycamptothecin glucuronide formation was observed for i1+i2 clones (mean of 53%) compared with the reference i1 cell line. In these clones, the i2 protein content varied greatly (38-263% relative to i1) and revealed two groups: 17 clones with i2 < i1 (60% ± 3%) and 6 clones with i2 ≥ i1 (153% ± 24%). The inhibition induced by i2 was more substantial for clones displaying i2 ≥ i1 (74.5%; P = 0.001) compared with those with i2 < i1 (45.5%). Coimmunoprecipitation supports a more substantial i1-i2 complex formation when i2 exceeds i1. We conclude that the relative abundance of regulatory i2 proteins has the potential to drastically alter the local drug metabolism in the cells, particularly when i2 surpasses the protein content of i1.

  15. Elevated glycogen synthase kinase-3 activity in Fragile X mice: Key metabolic regulator with evidence for treatment potential

    PubMed Central

    Min, Wenzhong William; Yuskaitis, Christopher J.; Yan, Qijiang; Sikorski, Christopher; Chen, Shengqiang; Jope, Richard S.; Bauchwitz, Robert P.

    2009-01-01

    Significant advances have been made in understanding the underlying defects of and developing potential treatments for Fragile X syndrome (FXS), the most common heritable mental retardation. It has been shown that neuronal metabotropic glutamate receptor 5 (mGluR5)-mediated signaling is affected in FX animal models, with consequent alterations in activity-dependent protein translation and synaptic spine functionality. We demonstrate here that a central metabolic regulatory enzyme, glycogen synthase kinase-3 (GSK3) is present in a form indicating elevated activity in several regions of the FX mouse brain. Furthermore, we show that selective GSK3 inhibitors, as well as lithium, are able to revert mutant phenotypes of the FX mouse. Lithium, in particular, remained effective with chronic administration, although its effects were reversible even when given from birth. The combination of an mGluR5 antagonist and GSK3 inhibitors was not additive. Instead, it was discovered that mGluR5 signaling and GSK3 activation in the FX mouse are coordinately elevated, with inhibition of mGluR5 leading to inhibition of GSK3. These findings raise the possibility that GSK3 is a fundamental and central component of FXS pathology, with a substantial treatment potential. PMID:18952114

  16. Strength of object representation: its key role in object-based attention for determining the competition result between Gestalt and top-down objects.

    PubMed

    Zhao, Jingjing; Wang, Yonghui; Liu, Donglai; Zhao, Liang; Liu, Peng

    2015-10-01

    It was found in previous studies that two types of objects (rectangles formed according to the Gestalt principle and Chinese words formed in a top-down fashion) can both induce an object-based effect. The aim of the present study was to investigate how the strength of an object representation affects the result of the competition between these two types of objects based on research carried out by Liu, Wang and Zhou [(2011) Acta Psychologica, 138(3), 397-404]. In Experiment 1, the rectangles were filled with two different colors to increase the strength of Gestalt object representation, and we found that the object effect changed significantly for the different stimulus types. Experiment 2 used Chinese words with various familiarities to manipulate the strength of the top-down object representation. As a result, the object-based effect induced by rectangles was observed only when the Chinese word familiarity was low. These results suggest that the strength of object representation determines the result of competition between different types of objects.

  17. Improving Instruction for Students with Learning Disabilities: The Results of Three Research Syntheses. Keys to Successful Learning: A National Summit on Research in Learning Disabilities.

    ERIC Educational Resources Information Center

    National Center for Learning Disabilities, Inc., New York, NY.

    This booklet presents three brief papers that summarize three meta-analytic research syntheses of instruction for students with learning disabilities. The first paper is "Intervention Research for Students with Learning Disabilities" by H. Lee Swanson. Findings that resulted from a review of 272 studies are grouped into those on most effective…

  18. New species of Diabrotica Chevrolat (Coleoptera: Chrysomelidae: Galerucinae) and a key to Diabrotica and related genera: results of a synopsis of North and Central American Diabrotica species

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The following 18 new species of Diabrotica are described and illustrated as a result of the synopsis of North and Centrla American species: D. barclayi nov. sp. Guatemala, D. caveyi nov. sp. Costa Rica, D. costaricensis nov. sp. Costa Rica, D. dmitryogloblini nov. sp. Mexico, D. duckworthae nov. sp....

  19. Recent Reanalysis Activities at ECMWF: Results from ERA-20C and Plans for ERA5

    NASA Astrophysics Data System (ADS)

    Dragani, R.; Hersbach, H.; Poli, P.; Pebeuy, C.; Hirahara, S.; Simmons, A.; Dee, D.

    2015-12-01

    This presentation will provide an overview of the most recent reanalysis activities performed at the European Centre for Medium-Range Weather Forecasts (ECMWF). A pilot reanalysis of the 20th-century (ERA-20C) has recently been completed. Funded through the European FP7 collaborative project ERA-CLIM, ERA-20C is part of a suite of experiments that also includes a model-only integration (ERA-20CM) and a land-surface reanalysis (ERA-20CL). Its data assimilation system is constrained by only surface observations obtained from ISPD (3.2.6) and ICOADS (2.5.1). Surface boundary conditions are provided by the Hadley Centre (HadISST2.1.0.0) and radiative forcing follows CMIP5 recommended data sets. First-guess uncertainty estimates are based on a 10-member ensemble of Data Assimilations, ERA-20C ensemble, run prior to ERA-20C using ten SST and sea-ice realizations from the Hadley Centre. In November 2014, the European Commission entrusted ECMWF to run on its behalf the Copernicus Climate Change Service (C3S) aiming at producing quality-assured information about the past, current and future states of the climate at both European and global scales. Reanalysis will be one of the main components of the C3S portfolio and the first one to be produced is a global modern era reanalysis (ERA5) covering the period from 1979 onwards. Based on a recent version of the ECMWF data assimilation system, ERA5 will replace the widely used ERA-Interim dataset. This new production will benefit from a much improved model, and better characterized and exploited observations compared to its predecessor. The first part of the presentation will focus on the ERA-20C production, provide an overview of its main characteristics and discuss some of the key results from its assessment. The second part of the talk will give an overview of ERA5, and briefly discuss some of its challenges.

  20. Holocene glacier activity on Kerguelen Island: preliminary results from a novel proglacial lake sediment record

    NASA Astrophysics Data System (ADS)

    Støren, Eivind; Bakke, Jostein; Arnaud, Fabien; Poulenard, Jérôme; Fanget, Bernard; Malet, Emmanuel; Sabatier, Pierre

    2016-04-01

    The Polar-regions are changing rapidly as greenhouse warming is continuing with huge impact on e.g. sea ice extent and snow cover. This change triggers teleconnections to low latitude areas challenging societies and human activity. We have, however, very little quantitative information of past climate in the Polar-regions that can be used to evaluate the potential responses and the response patterns to forcing changes and changes in boundary conditions. Whatever anthropogenic changes may occur in the future, they will be superimposed on, and interact with, natural climate variations due to all the forcing we are aware of. This means we need to better document past climate/environmental variability of the Polar-regions. Especially in the Southern Ocean there are few time series recording past climate due to few suitable land areas and the few Sub-Antarctic Islands is remote and has cumbersome logistics. Continuous terrestrial records from this region are therefore urgently needed for constraining future scenarios from earth system models. Glaciers and ice caps are still ubiquitous in the Polar-regions, although they are rapidly shrinking due to the on-going warming. The continuous sedimentary records produced by glaciers, which are stored in downstream lakes, represent supreme archives of past variability wherefrom quantitative information of key climate system components can be extracted. Kerguelen Island is located within the Antarctic Circumpolar Current and the Southern Westerly wind belt and contains several glaciers and smaller ice caps. Terrestrial archives recording past history of the glaciers at Kerguelen thus have a unique potential to record past changes in oceanic and atmospheric circulation patterns from southern mid-latitudes. Here we present preliminary results from the first distal glacier-fed lake that is sampled from Kerguelen Island. A 2.8 m long sediment core was obtained from Lac Guynemer (121masl.) located at the Peninsule Loranchet at the

  1. Low dose cadmium poisoning results in sustained ERK phosphorylation and caspase activation

    SciTech Connect

    Martin, Patrick . E-mail: pmartin@unice.fr; Poggi, Marie Christine . E-mail: poggi@unice.fr; Chambard, Jean Claude . E-mail: chambard@unice.fr; Boulukos, Kim E. . E-mail: boulukos@unice.fr; Pognonec, Philippe . E-mail: pognonec@unice.fr

    2006-11-24

    Cadmium poisoning has been known to result in a wide variety of cellular responses, including oxidative stress and kinase activation. It has been reported that ERK is activated following acute cadmium exposure, and this response is commonly seen as a classical ERK survival mechanism. Here, we analyzed different cell types for their responses to low concentrations of cadmium poisoning. We found that there is an association between cell susceptibility to cadmium toxicity and ERK activation. This activation is atypical, since it consists of a sustained ERK phosphorylation, that lasts up to 6 days post stimulation. This activation is associated with the appearance of cleaved caspases 8 and 3, processed PARP, and irreversible damage. Pharmacological inhibition of ERK phosphorylation results in the ability of cells to resist cadmium poisoning. Our data indicate that low cadmium concentrations result in an unconventional ERK sustained phosphorylation, which in turn leads to death signaling.

  2. The Saccharomyces cerevisiae Leu3 protein activates expression of GDH1, a key gene in nitrogen assimilation.

    PubMed

    Hu, Y; Cooper, T G; Kohlhaw, G B

    1995-01-01

    The Leu3 protein of Saccharomyces cerevisiae has been shown to be a transcriptional regulator of genes encoding enzymes of the branched-chain amino acid biosynthetic pathways. Leu3 binds to upstream activating sequences (UASLEU) found in the promoters of LEU1, LEU2, LEU4, ILV2, and ILV5. In vivo and in vitro studies have shown that activation by Leu3 requires the presence of alpha-isopropylmalate. In at least one case (LEU2), Leu3 actually represses basal-level transcription when alpha-isopropylmalate is absent. Following identification of a UASLEU-homologous sequence in the promoter of GDH1, the gene encoding NADP(+)-dependent glutamate dehydrogenase, we demonstrate that Leu3 specifically interacts with this UASLEU element. We then show that Leu3 is required for full activation of the GDH1 gene. First, the expression of a GDH1-lacZ fusion gene is three- to sixfold lower in a strain lacking the LEU3 gene than in an isogenic LEU3+ strain. Expression is restored to near-normal levels when the leu3 deletion cells are transformed with a LEU3-bearing plasmid. Second, a significant decrease in GDH1-lacZ expression is also seen when the UASLEU of the GDH1-lacZ construct is made nonfunctional by mutation. Third, the steady-state level of GDH1 mRNA decreases about threefold in leu3 null cells. The decrease in GDH1 expression in leu3 null cells is reflected in a diminished specific activity of NADP(+)-dependent glutamate dehydrogenase. We also demonstrate that the level of GDH1-lacZ expression correlates with the cells' ability to generate alpha-isopropylmalate and is lowest in cells unable to produce alpha-isopropylmalate. We conclude that GDH1, which plays an important role in the assimilation of ammonia in yeast cells, is, in part, activated by a Leu3-alpha-isopropylmalate complex. This conclusion suggests that Leu3 participates in transcriptional regulation beyond the branched-chain amino acid biosynthetic pathways.

  3. KEY COMPARISON: BIPM comparison BIPM.RI(II)-K1.Yb-169 of activity measurements of the radionuclide 169Yb and links for the 1997 regional comparison EUROMET.RI(II)-K2.Yb-169

    NASA Astrophysics Data System (ADS)

    Ratel, G.; Michotte, C.; Coursol, N.; Morel, J.

    2004-01-01

    Since 1978, six national metrology institutes (NMI) have submitted eleven samples of known activity of 169Yb to the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures (BIPM), with comparison identifier BIPM.RI(II)-K1.Yb-169. The activities ranged from about 200 kBq to 46 MBq. The degrees of equivalence between each equivalent activity measured in the SIR and the key comparison reference value (KCRV) have been calculated and the results are given in the form of a matrix for four NMIs. A graphical presentation is also given. The results of a EUROMET regional comparison, comparison identifier EUROMET.RI(II)-K2.Yb-169, completed in 1997 for this radionuclide have been linked to the SIR results through those of the BNM-LNHB and the IRA. This has enabled five other NMIs and an international laboratory to have degrees of equivalence in the KCDB and two other NMIs to update their earlier results in the SIR. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by Section II of the Consultative Committee for Ionizing Radiation (CCRI(II)), according to the provisions of the Mutual Recognition Arrangement (MRA).

  4. HrcT is a key component of the type III secretion system in Xanthomonas spp. and also regulates the expression of the key hrp transcriptional activator HrpX.

    PubMed

    Liu, Zhi-Yang; Zou, Li-Fang; Xue, Xiao-Bo; Cai, Lu-Lu; Ma, Wen-Xiu; Xiong, Li; Ji, Zhi-Yuan; Chen, Gong-You

    2014-07-01

    The type III secretion system (T3SS), encoded by hrp (hypersensitive response and pathogenicity) genes in Gram-negative phytopathogenic bacteria, delivers repertoires of T3SS effectors (T3SEs) into plant cells to trigger the hypersensitive response (HR) in nonhost or resistant-host plants and promote pathogenicity in susceptible plants. The expression of hrp genes in Xanthomonas is regulated by two key regulatory proteins, HrpG and HrpX. However, the interactions between hrp gene products in directing T3SE secretion are largely unknown. Here we demonstrated that HrcT of X. oryzae pv. oryzicola functions as a T3SS component and positively regulates the expression of hrpX. Transcription of hrcT occurs via two distinct promoters; one (T1) is with the hrpB operon and the second (T3) within hrpB7 Via either promoter T1 or T3, the defect in Hrp phenotype by hrcT deletion was corrected in the presence of hrcT only from Xanthomonas species but not from other phytopathogenic bacteria. An N-terminally truncated HrcT was able to bind the hrpX promoter and activate the expression of hrpX, supporting that HrcT is a positive regulator of hrpX. A revised model showing the regulatory interactions between HrcT, HrpX, and HrpG is proposed.

  5. Does Pedometer Goal Setting Improve Physical Activity among Native Elders? Results from a Randomized Pilot Study

    ERIC Educational Resources Information Center

    Sawchuk, Craig N.; Russo, Joan E.; Charles, Steve; Goldberg, Jack; Forquera, Ralph; Roy-Byrne, Peter; Buchwald, Dedra

    2011-01-01

    We examined if step-count goal setting resulted in increases in physical activity and walking compared to only monitoring step counts with pedometers among American Indian/Alaska Native elders. Outcomes included step counts, self-reported physical activity and well-being, and performance on the 6-minute walk test. Although no significant…

  6. A Study Of The Radionuclidic Content Of The Environmental Samples Resulting From NIPNE Activities

    SciTech Connect

    Stochioiu, Ana I.; Bercea, Sorin I.; Ivan, Constantin G.; Dumitru, Octavian R.; Pantelica, Ana I.

    2007-04-23

    The results of alpha, beta, gamma global activity measurements and gamma spectrometric measurements are presented. For more detailed characterization of samples, gamma-spectrometric measurement, implying identification of radionuclides and their activities are carried-out on significant ambiental annual samples.

  7. Oxidative stress and hepatic stellate cell activation are key events in arsenic induced liver fibrosis in mice

    SciTech Connect

    Ghatak, Subhadip; Biswas, Ayan; Dhali, Gopal Krishna; Chowdhury, Abhijit; Boyer, James L.; Santra, Amal

    2011-02-15

    Arsenic is an environmental toxicant and carcinogen. Exposure to arsenic is associated with development of liver fibrosis and portal hypertension through ill defined mechanisms. We evaluated hepatic fibrogenesis after long term arsenic exposure in a murine model. BALB/c mice were exposed to arsenic by daily gavages of 6 {mu}g/gm body weight for 1 year and were evaluated for markers of hepatic oxidative stress and fibrosis, as well as pro-inflammatory, pro-apoptotic and pro-fibrogenic factors at 9 and 12 months. Hepatic NADPH oxidase activity progressively increased in arsenic exposure with concomitant development of hepatic oxidative stress. Hepatic steatosis with occasional collection of mononuclear inflammatory cells and mild portal fibrosis were the predominant liver lesion observed after 9 months of arsenic exposure, while at 12 months, the changes included mild hepatic steatosis, inflammation, necrosis and significant fibrosis in periportal areas. The pathologic changes in the liver were associated with markers of hepatic stellate cells (HSCs) activation, matrix reorganization and fibrosis including {alpha}-smooth muscle actin, transforming growth factor-{beta}1, PDGF-R{beta}, pro-inflammatory cytokines and enhanced expression of tissue inhibitor of metalloproteinase-1 and pro({alpha}) collagen type I. Moreover, pro-apoptotic protein Bax was dominantly expressed and Bcl-2 was down-regulated along with increased number of TUNEL positive hepatocytes in liver of arsenic exposed mice. Furthermore, HSCs activation due to increased hepatic oxidative stress observed after in vivo arsenic exposure was recapitulated in co-culture model of isolated HSCs and hepatocytes exposed to arsenic. These findings have implications not only for the understanding of the pathology of arsenic related liver fibrosis but also for the design of preventive strategies in chronic arsenicosis.

  8. Rooibos flavonoids inhibit the activity of key adrenal steroidogenic enzymes, modulating steroid hormone levels in H295R cells.

    PubMed

    Schloms, Lindie; Swart, Amanda C

    2014-03-24

    Major rooibos flavonoids--dihydrochalcones, aspalathin and nothofagin, flavones--orientin and vitexin, and a flavonol, rutin, were investigated to determine their influence on the activity of adrenal steroidogenic enzymes, 3β-hydroxysteroid dehydrogenase (3βHSD2) and cytochrome P450 (P450) enzymes, P450 17α-hydroxylase/17,20-lyase (CYP17A1), P450 21-hydroxylase (CYP21A2) and P450 11β-hydroxylase (CYP11B1). All the flavonoids inhibited 3βHSD2 and CYP17A1 significantly, while the inhibition of downstream enzymes, CYP21A2 and CYP11B1, was both substrate and flavonoid specific. The dihydrochalcones inhibited the activity of CYP21A2, but not that of CYP11B1. Although rutin, orientin and vitexin inhibited deoxycortisol conversion by CYP11B1 significantly, inhibition of deoxycorticosterone was <20%. These three flavonoids were unable to inhibit CYP21A2, with negligible inhibition of deoxycortisol biosynthesis only. Rooibos inhibited substrate conversion by CYP17A1 and CYP21A2, while the inhibition of other enzyme activities was <20%. In H295R cells, rutin had the greatest inhibitory effect on steroid production upon forskolin stimulation, reducing total steroid output 2.3-fold, while no effect was detected under basal conditions. Nothofagin and vitexin had a greater inhibitory effect on overall steroid production compared to aspalathin and orientin, respectively. The latter compounds contain two hydroxyl groups on the B ring, while nothofagin and vitexin contain a single hydroxyl group. In addition, all of the flavonoids are glycosylated, albeit at different positions--dihydrochalcones at C3' and flavones at C8 on ring A, while rutin, a larger molecule, has a rutinosyl moiety at C3 on ring C. Structural differences regarding the number and position of hydroxyl and glucose moieties as well as structural flexibility could indicate different mechanisms by which these flavonoids influence the activity of adrenal steroidogenic enzymes.

  9. Do Media Use and Physical Activity Compete in Adolescents? Results of the MoMo Study

    PubMed Central

    Spengler, Sarah; Mess, Filip; Woll, Alexander

    2015-01-01

    Purpose The displacement hypothesis predicts that physical activity and media use compete in adolescents; however, findings are inconsistent. A more differentiated approach at determining the co-occurrence of physical activity and media use behaviors within subjects may be warranted. The aim of this study was to determine the co-occurrence of physical activity and media use by identifying clusters of adolescents with specific behavior patterns including physical activity in various settings (school, sports club, leisure time) and different types of media use (watching TV, playing console games, using PC / Internet). Methods Cross-sectional data of 2,083 adolescents (11–17 years) from all over Germany were collected between 2009 and 2012 in the Motorik-Modul Study. Physical activity and media use were self-reported. Cluster analyses (Ward’s method and K-means analysis) were used to identify behavior patterns of boys and girls separately. Results Eight clusters were identified for boys and seven for girls. The clusters demonstrated that a high proportion of boys (33%) as well as girls (42%) show low engagement in both physical activity and media use, irrespective of setting or type of media. Other adolescents are engaged in both behaviors, but either physical activity (35% of boys, 27% of girls) or media use (31% of boys and girls) predominates. These adolescents belong to different clusters, whereat in most clusters either one specific setting of physical activity or a specific combination of different types of media predominates. Conclusion The results of this study support to some extent the hypothesis that media use and physical activity compete: Very high media use occurred with low physical activity behavior, but very high activity levels co-occurred with considerable amounts of time using any media. There was no evidence that type of used media was related to physical activity levels, neither setting of physical activity was related to amount of media use

  10. A highly potent agonist to protease-activated receptor-2 reveals apical activation of the airway epithelium resulting in Ca2+-regulated ion conductance

    PubMed Central

    Sherwood, Cara L.; Daines, Michael O.; Price, Theodore J.; Vagner, Josef

    2014-01-01

    The airway epithelium provides a barrier that separates inhaled air and its various particulates from the underlying tissues. It provides key physiological functions in both sensing the environment and initiating appropriate innate immune defenses to protect the lung. Protease-activated receptor-2 (PAR2) is expressed both apically and basolaterally throughout the airway epithelium. One consequence of basolateral PAR2 activation is the rapid, Ca2+-dependent ion flux that favors secretion in the normally absorptive airway epithelium. However, roles for apically expressed PAR2 activation have not been demonstrated, in part due to the lack of specific, high-potency PAR2 ligands. In the present study, we used the newly developed PAR2 ligand 2at-LIGRLO(PEG3-Pam)-NH2 in combination with well-differentiated, primary cultured airway epithelial cells from wild-type and PAR2−/− mice to examine the physiological role of PAR2 in the conducting airway after apical activation. Using digital imaging microscopy of intracellular Ca2+ concentration changes, we verified ligand potency on PAR2 in primary cultured airway cells. Examination of airway epithelial tissue in an Ussing chamber showed that apical activation of PAR2 by 2at-LIGRLO(PEG3-Pam)-NH2 resulted in a transient decrease in transepithelial resistance that was due to increased apical ion efflux. We determined pharmacologically that this increase in ion conductance was through Ca2+-activated Cl− and large-conductance K+ channels that were blocked with a Ca2+-activated Cl− channel inhibitor and clotrimazole, respectively. Stimulation of Cl− efflux via PAR2 activation at the airway epithelial surface can increase airway surface liquid that would aid in clearing the airway of noxious inhaled agents. PMID:25143347

  11. Alkaline Leaching of Key, Non-Radioactive Components from Simulants and Hanford Tank Sludge 241-S-110: Results of FY01 Studies

    SciTech Connect

    Rapko, Brian M.; Vienna, John D.; Sinkov, Serguei I.; Kim, Jinseong; Cisar, Alan J.

    2002-09-10

    This study addressed three aspects in selected alkaline leaching: first, the use of oxidants persulfate, permanganate, and ferrate as selective chromium-leaching agents from washed Hanford Tank S-110 solids under varying conditions of hydroxide concentration, temperature, and time was investigated. Second, the selective dissolution of solids containing mercury(II) oxide under alkaline conditions was examined. Various compounds were studied for their effectiveness in dissolving mercury under varying conditions of time, temperature, and hydroxide concentration in the leachate. Three compounds were studied: cysteine, iodide, and diethyldithiophosphoric acid (DEDTPA). Finally, the possibility of whether an oxidant bound to an anion-exchange resin can be used to effectively oxidize chromium(III) in alkaline solutions was addressed. The experimental results remain ambiguous to date; further work is required to reach any definitive conclusions as to the effectiveness of this approach.

  12. Mortality as a key driver of the spatial distribution of aboveground biomass in Amazonian forests: results from a Dynamic Vegetation Model

    NASA Astrophysics Data System (ADS)

    Delbart, N.; Ciais, P.; Chave, J.; Viovy, N.; Malhi, Y.; Le Toan, T.

    2010-04-01

    Dynamic Vegetation Models (DVMs) simulate energy, water and carbon fluxes between the ecosystem and the atmosphere, between the vegetation and the soil, and between plant organs. They also estimate the potential biomass of a forest in equilibrium having grown under a given climate and atmospheric CO2 level. In this study, we evaluate the above ground woody biomass (AGWB) and the above ground woody Net Primary Productivity (NPPAGW) simulated by the DVM ORCHIDEE across Amazonian forests, by comparing the simulation results to a large set of ground measurements (220 sites for biomass, 104 sites for NPPAGW). We found that the NPPAGW is on average overestimated by 63%. We also found that the fraction of biomass that is lost through mortality is 85% too high. These model biases nearly compensate each other to give an average simulated AGWB close to the ground measurement average. Nevertheless, the simulated AGWB spatial distribution differs significantly from the observations. Then, we analyse the discrepancies in biomass with regards to discrepancies in NPPAGW and those in the rate of mortality. When we correct for the error in NPPAGW, the errors on the spatial variations in AGWB are exacerbated, showing clearly that a large part of the misrepresentation of biomass comes from a wrong modelling of mortality processes. Previous studies showed that Amazonian forests with high productivity have a higher mortality rate than forests with lower productivity. We introduce this relationship, which results in strongly improved modelling of biomass and of its spatial variations. We discuss the possibility of modifying the mortality modelling in ORCHIDEE, and the opportunity to improve forest productivity modelling through the integration of biomass measurements, in particular from remote sensing.

  13. Mortality as a key driver of the spatial distribution of aboveground biomass in Amazonian forest: results from a dynamic vegetation model

    NASA Astrophysics Data System (ADS)

    Delbart, N.; Ciais, P.; Chave, J.; Viovy, N.; Malhi, Y.; Le Toan, T.

    2010-10-01

    Dynamic Vegetation Models (DVMs) simulate energy, water and carbon fluxes between the ecosystem and the atmosphere, between the vegetation and the soil, and between plant organs. They also estimate the potential biomass of a forest in equilibrium having grown under a given climate and atmospheric CO2 level. In this study, we evaluate the Above Ground Woody Biomass (AGWB) and the above ground woody Net Primary Productivity (NPPAGW) simulated by the DVM ORCHIDEE across Amazonian forests, by comparing the simulation results to a large set of ground measurements (220 sites for biomass, 104 sites for NPPAGW). We found that the NPPAGW is on average overestimated by 63%. We also found that the fraction of biomass that is lost through mortality is 85% too high. These model biases nearly compensate each other to give an average simulated AGWB close to the ground measurement average. Nevertheless, the simulated AGWB spatial distribution differs significantly from the observations. Then, we analyse the discrepancies in biomass with regards to discrepancies in NPPAGW and those in the rate of mortality. When we correct for the error in NPPAGW, the errors on the spatial variations in AGWB are exacerbated, showing clearly that a large part of the misrepresentation of biomass comes from a wrong modelling of mortality processes. Previous studies showed that Amazonian forests with high productivity have a higher mortality rate than forests with lower productivity. We introduce this relationship, which results in strongly improved modelling of biomass and of its spatial variations. We discuss the possibility of modifying the mortality modelling in ORCHIDEE, and the opportunity to improve forest productivity modelling through the integration of biomass measurements, in particular from remote sensing.

  14. Incomplete suppression of distractor-related activity in the frontal eye field results in curved saccades.

    PubMed

    McPeek, Robert M

    2006-11-01

    Saccades in the presence of distractors show significant trajectory curvature. Based on previous work in the superior colliculus (SC), we speculated that curvature arises when a movement is initiated before competition between the target and distractor goals has been fully resolved. To test this hypothesis, we recorded frontal eye field (FEF) activity for curved and straight saccades in search. In contrast to the SC, activity in FEF is normally poorly correlated with saccade dynamics. However, the FEF, like the SC, is involved in target selection. Thus if curvature is caused by incomplete target selection, we expect to see its neural correlates in the FEF. We found that saccades that curve toward a distractor are accompanied by an increase in perisaccadic activity of FEF neurons coding the distractor location, and saccades that curve away are accompanied by a decrease in activity. In contrast, for FEF neurons coding the target location, there is no significant difference in activity between curved and straight saccades. To establish that the distractor-related activity is causally related to saccade curvature, we applied microstimulation to sites in the FEF before saccades to targets presented without distractors. The stimulation was subthreshold for evoking saccades and the temporal structure of the stimulation train resembled the activity recorded for curved saccades. The resulting movements curved toward the location coded by the stimulation site. These results support the idea that saccade curvature results from incomplete suppression of distractor-related activity during target selection.

  15. Cooperative hydration effect causes thermal unfolding of proteins and water activity plays a key role in protein stability in solutions.

    PubMed

    Miyawaki, Osato; Dozen, Michiko; Hirota, Kaede

    2016-08-01

    The protein unfolding process observed in a narrow temperature range was clearly explained by evaluating the small difference in the enthalpy of hydrogen-bonding between amino acid residues and the hydration of amino acid residue separately. In aqueous solutions, the effect of cosolute on the protein stability is primarily dependent on water activity, aw, the role of which has been long neglected in the literature. The effect of aw on protein stability works as a power law so that a small change in aw is amplified substantially through the cooperative hydration effect. In the present approach, the role of hydrophobic interaction stands behind. This affects protein stability indirectly through the change in solution structure caused by the existence of cosolute.

  16. A key parameter on the adsorption of diluted aniline solutions with activated carbons: The surface oxygen content.

    PubMed

    Pardo, Beatrice; Ferrer, Nabí; Sempere, Julià; Gonzalez-Olmos, Rafael

    2016-11-01

    A total of 11 different commercial activated carbons (AC) with well characterized textural properties and oxygen surface content were tested as adsorbents for the removal of aniline as a target water pollutant. The maximum adsorption capacity of aniline for the studied AC was from 138.9 to 257.9 mg g(-1) at 296.15 K and it was observed to be strongly related to the textural properties of the AC, mainly with the BET surface area and the micropore volume. It was not observed any influence of the oxygen surface content of the AC on the maximum adsorption capacity. However, it was found that at low aniline aqueous concentration, the presence of oxygen surface groups plays a dominant role during the adsorption. A high concentration of oxygen surface groups, mainly carboxylic and phenolic groups, decreases the aniline adsorption regardless of the surface area of the AC.

  17. NETosis and lack of DNase activity are key factors in Echis carinatus venom-induced tissue destruction

    PubMed Central

    Katkar, Gajanan D.; Sundaram, Mahalingam S.; NaveenKumar, Somanathapura K.; Swethakumar, Basavarajaiah; Sharma, Rachana D.; Paul, Manoj; Vishalakshi, Gopalapura J.; Devaraja, Sannaningaiah; Girish, Kesturu S.; Kemparaju, Kempaiah

    2016-01-01

    Indian Echis carinatus bite causes sustained tissue destruction at the bite site. Neutrophils, the major leukocytes in the early defence process, accumulate at the bite site. Here we show that E. carinatus venom induces neutrophil extracellular trap (NET) formation. The NETs block the blood vessels and entrap the venom toxins at the injection site, promoting tissue destruction. The stability of NETs is attributed to the lack of NETs-degrading DNase activity in E. carinatus venom. In a mouse tail model, mice co-injected with venom and DNase 1, and neutropenic mice injected with the venom, do not develop NETs, venom accumulation and tissue destruction at the injected site. Strikingly, venom-induced mice tail tissue destruction is also prevented by the subsequent injection of DNase 1. Thus, our study suggests that DNase 1 treatment may have a therapeutic potential for preventing the tissue destruction caused by snake venom. PMID:27093631

  18. IGF-I activity may be a key determinant of stroke risk--a cautionary lesson for vegans.

    PubMed

    McCarty, M F

    2003-09-01

    IGF-I acts on vascular endothelium to activate nitric oxide synthase, thereby promoting vascular health; there is reason to believe that this protection is especially crucial to the cerebral vasculature, helping to ward off thrombotic strokes. IGF-I may also promote the structural integrity of cerebral arteries, thereby offering protection from hemorrhagic stroke. These considerations may help to explain why tallness is associated with low stroke risk, whereas growth hormone deficiency increases stroke risk--and why age-adjusted stroke mortality has been exceptionally high in rural Asians eating quasi-vegan diets, but has been declining steadily in Asia as diets have become progressively higher in animal products. There is good reason to suspect that low-fat vegan diets tend to down-regulate systemic IGF-I activity; this effect would be expected to increase stroke risk in vegans. Furthermore, epidemiology suggests that low serum cholesterol, and possibly also a low dietary intake of saturated fat--both characteristic of those adopting low-fat vegan diets--may also increase stroke risk. Vegans are thus well advised to adopt practical countermeasures to minimize stroke risk--the most definitive of which may be salt restriction. A high potassium intake, aerobic exercise training, whole grains, moderate alcohol consumption, low-dose aspirin, statin or policosanol therapy, green tea, and supplementation with fish oil, taurine, arginine, and B vitamins--as well as pharmacotherapy of hypertension if warranted--are other practical measures for lowering stroke risk. Although low-fat vegan diets may markedly reduce risk for coronary disease, diabetes, and many common types of cancer, an increased risk for stroke may represent an 'Achilles heel'. Nonetheless, vegans have the potential to achieve a truly exceptional 'healthspan' if they face this problem forthrightly by restricting salt intake and taking other practical measures that promote cerebrovascular health.

  19. Essential role of PSM/SH2-B variants in insulin receptor catalytic activation and the resulting cellular responses.

    PubMed

    Zhang, Manchao; Deng, Youping; Tandon, Ruchi; Bai, Cheng; Riedel, Heimo

    2008-01-01

    The positive regulatory role of PSM/SH2-B downstream of various mitogenic receptor tyrosine kinases or gene disruption experiments in mice support a role of PSM in the regulation of insulin action. Here, four alternative PSM splice variants and individual functional domains were compared for their role in the regulation of specific metabolic insulin responses. We found that individual PSM variants in 3T3-L1 adipocytes potentiated insulin-mediated glucose and amino acid transport, glycogenesis, lipogenesis, and key components in the metabolic insulin response including p70 S6 kinase, glycogen synthase, glycogen synthase kinase 3 (GSK3), Akt, Cbl, and IRS-1. Highest activity was consistently observed for PSM alpha, followed by beta, delta, and gamma with decreasing activity. In contrast, dominant-negative peptide mimetics of the PSM Pro-rich, pleckstrin homology (PH), or src homology 2 (SH2) domains inhibited any tested insulin response. Potentiation of the insulin response originated at the insulin receptor (IR) kinase level by PSM variant-specific regulation of the Km (ATP) whereas the Vmax remained unaffected. IR catalytic activation was inhibited by peptide mimetics of the PSM SH2 or dimerization domain (DD). Either peptide should disrupt the complex of a PSM dimer linked to IR via SH2 domains as proposed for PSM activation of tyrosine kinase JAK2. Either peptide abolished downstream insulin responses indistinguishable from PSM siRNA knockdown. Our results implicate an essential role of the PSM variants in the activation of the IR kinase and the resulting metabolic insulin response. PSM variants act as internal IR ligands that in addition to potentiating the insulin response stimulate IR catalytic activation even in the absence of insulin.

  20. Late Quaternary reef growth history of Les Saintes submarine plateau: a key to constrain active faulting kinematics in Guadeloupe (FWI)

    NASA Astrophysics Data System (ADS)

    Leclerc, F.; Feuillet, N.; Deplus, C.; Cabioch, G.; Tapponnier, P.; LeBrun, J.; Bazin, S.; Beauducel, F.; Boudon, G.; Le Friant, A.; De Min, L.; Melezan, D.

    2012-12-01

    hazard. Joint analysis of the aftershocks sequence and the fault map provide a good image of the fault system recent activity. Finally, we deduced fault kinematics with respect to Holocene reef demise timing, and obtained a mean slip rate of several tenth of mm/yr on each fault, comparable to the slip rate of the near active Morne-Piton fault. Thus, the fault system could generate a Mw 6 earthquake every 250 yrs.

  1. Heterolytic Activation of C-H Bonds on Cr(III)-O Surface Sites Is a Key Step in Catalytic Polymerization of Ethylene and Dehydrogenation of Propane.

    PubMed

    Conley, Matthew P; Delley, Murielle F; Núñez-Zarur, Francisco; Comas-Vives, Aleix; Copéret, Christophe

    2015-06-01

    We describe the reactivity of well-defined chromium silicates toward ethylene and propane. The initial motivation for this study was to obtain a molecular understanding of the Phillips polymerization catalyst. The Phillips catalyst contains reduced chromium sites on silica and catalyzes the polymerization of ethylene without activators or a preformed Cr-C bond. Cr(II) sites are commonly proposed active sites in this catalyst. We synthesized and characterized well-defined chromium(II) silicates and found that these materials, slightly contaminated with a minor amount of Cr(III) sites, have poor polymerization activity and few active sites. In contrast, chromium(III) silicates have 1 order of magnitude higher activity. The chromium(III) silicates initiate polymerization by the activation of a C-H bond of ethylene. Density functional theory analysis of this process showed that the C-H bond activation step is heterolytic and corresponds to a σ-bond metathesis type process. The same well-defined chromium(III) silicate catalyzes the dehydrogenation of propane at elevated temperatures with activities similar to those of a related industrial chromium-based catalyst. This reaction also involves a key heterolytic C-H bond activation step similar to that described for ethylene but with a significantly higher energy barrier. The higher energy barrier is consistent with the higher pKa of the C-H bond in propane compared to the C-H bond in ethylene. In both cases, the rate-determining step is the heterolytic C-H bond activation.

  2. Influence of mesophase activation conditions on the specific capacitance of the resulting carbons

    NASA Astrophysics Data System (ADS)

    Mora, E.; Ruiz, V.; Santamaría, R.; Blanco, C.; Granda, M.; Menéndez, R.; Juarez-Galán, J. M.; Rodríguez-Reinoso, F.

    Mesophase pitch AR24 was directly activated with KOH using different proportions of the activating agent and activation temperatures, to study the effect on the textural characteristics of the resultant activated carbons and how these characteristics influence their behaviour as electrodes in supercapacitors. The textural properties of the activated carbons were studied by gas adsorption and immersion calorimetry. The results indicate that all the carbons produced were mainly microporous, with pore size around 1 nm. The behaviour of these carbons as electrodes in supercapacitors was studied from galvanostatic charge-discharge cycles. The specific capacitance values obtained were very high, reaching 400 and 200 F g -1 at low and high current densities respectively, for the sample activated with (5:1) KOH to mesophase ratio. Nevertheless, the reasons for this high capacitance values cannot be explained only on the basis of the textural characteristics of the activated carbons, as the results indicated that other factors might be also playing a significant role in their electrochemical behaviour.

  3. Uiavy sobi: uchnivs'ski zoshyt [and] vidpovidi do uchnivs'koho zoshyta (Just Imagine: Activity Book [and] Answer Key to Student Activity Book). Collage 3: A Ukrainian Language Development Series.

    ERIC Educational Resources Information Center

    Boruszczak, Bohdan, Comp.

    This workbook is one of four intermediate- to advanced-level activity books in a series for teaching the Ukrainian language to both native speakers and second language learners. It offers a selection of exercises, vocabulary builders, dialogs, and writing exercises for language skill development. A teacher's answer key to accompany the activity…

  4. Tsikave: uchnivs'ski zoshyt [and] vidpovidi do uchnivs'koho zoshyta (It's Interesting: Activity Book [and] Answer Key to Student Activity Book). Collage 3: A Ukrainian Language Development Series.

    ERIC Educational Resources Information Center

    Boruszczak, Bohdan, Comp.

    This workbook is one of four intermediate- to advanced-level activity books in a series for teaching the Ukrainian language to both native speakers and second language learners. It offers a selection of exercises, vocabulary builders, dialogs, and writing exercises for language skill development. A teacher's answer key to accompany the activity…

  5. I smikh, i plach: uchnivs'ski zoshyt [and] vidpovidi do uchnivs'koho zoshyta (Laughter and Tears: Activity Book [and] Answer Key to Student Activity Book). Collage 3: A Ukrainian Language Development Series.

    ERIC Educational Resources Information Center

    Boruszczak, Bohdan, Comp.

    This workbook is one of four intermediate- to advanced-level activity books in a series for teaching the Ukrainian language to both native speakers and second language learners. It offers a selection of exercises, vocabulary builders, dialogs, and writing exercises for language skill development. A teacher's answer key to accompany the activity…

  6. Dva shliakhy: uchnivs'ski zoshyt [and] vidpovidi do uchnivs'koho zoshyta (Two Paths: Student Activity Book [and] Answer Key to Student Activity Book). Collage 3: A Ukrainian Language Development Series.

    ERIC Educational Resources Information Center

    Boruszczak, Bohdan, Comp.

    This workbook is one of four intermediate- to advanced-level activity books in a series for teaching the Ukrainian language to both native speakers and second language learners. It offers a selection of exercises, vocabulary builders, dialogs, and writing exercises for language skill development. A teacher's answer key to accompany the activity…

  7. Modification of Pulsed Electric Field Conditions Results in Distinct Activation Profiles of Platelet-Rich Plasma

    PubMed Central

    Frelinger, Andrew L.; Gerrits, Anja J.; Garner, Allen L.; Torres, Andrew S.; Caiafa, Antonio; Morton, Christine A.; Berny-Lang, Michelle A.; Carmichael, Sabrina L.; Neculaes, V. Bogdan; Michelson, Alan D.

    2016-01-01

    Background Activated autologous platelet-rich plasma (PRP) used in therapeutic wound healing applications is poorly characterized and standardized. Using pulsed electric fields (PEF) to activate platelets may reduce variability and eliminate complications associated with the use of bovine thrombin. We previously reported that exposing PRP to sub-microsecond duration, high electric field (SMHEF) pulses generates a greater number of platelet-derived microparticles, increased expression of prothrombotic platelet surfaces, and differential release of growth factors compared to thrombin. Moreover, the platelet releasate produced by SMHEF pulses induced greater cell proliferation than plasma. Aims To determine whether sub-microsecond duration, low electric field (SMLEF) bipolar pulses results in differential activation of PRP compared to SMHEF, with respect to profiles of activation markers, growth factor release, and cell proliferation capacity. Methods PRP activation by SMLEF bipolar pulses was compared to SMHEF pulses and bovine thrombin. PRP was prepared using the Harvest SmartPreP2 System from acid citrate dextrose anticoagulated healthy donor blood. PEF activation by either SMHEF or SMLEF pulses was performed using a standard electroporation cuvette preloaded with CaCl2 and a prototype instrument designed to take into account the electrical properties of PRP. Flow cytometry was used to assess platelet surface P-selectin expression, and annexin V binding. Platelet-derived growth factor (PDGF), vascular endothelial growth factor (VEGF), endothelial growth factor (EGF) and platelet factor 4 (PF4), and were measured by ELISA. The ability of supernatants to stimulate proliferation of human epithelial cells in culture was also evaluated. Controls included vehicle-treated, unactivated PRP and PRP with 10 mM CaCl2 activated with 1 U/mL bovine thrombin. Results PRP activated with SMLEF bipolar pulses or thrombin had similar light scatter profiles, consistent with the

  8. Modeling synchronous theta activity in the medial septum: key role of local communications between different cell populations.

    PubMed

    Mysin, Ivan E; Kitchigina, Valentina F; Kazanovich, Yakov

    2015-08-01

    It is widely believed that the theta rhythm in the hippocampus is caused by the rhythmic input from the medial septum-diagonal band of Broca (MSDB). The main MSDB output is formed by GABAergic projection neurons which are divided into two subpopulations and fire at different phases of the hippocampal theta rhythm. The MSDB also contains projection cholinergic, glutamatergic, and non-projection GABAergic neurons. These cell populations innervate each other and also GABAergic projection neurons and participate in the formation of the synchronous rhythmic output to the hippocampus. The purpose of this study is to work out a model of interactions between all neural populations of the MSDB that underlie the formation of the synchronous septal theta signal. The model is built from biologically plausible neurons of the Hodgkin-Huxley type and its architecture reflects modern data on the morphology of neural connections in the MSDB. The model satisfies the following requirements: (1) a large portion of neurons is fast-spiking; (2) the subpopulations of GABAergic projection neurons contain endogenous pacemaker neurons; (3) the phase shift of activity between subpopulations of GABAergic projection neurons is equal to about 150°; and (4) the strengths of bidirectional connections between the subpopulations of GABAergic projection cells are different. It is shown that the theta rhythm generation can be performed by a system of glutamatergic and GABAergic non-projection neurons. We also show that bursting pacemaker neurons in the subpopulation of projection GABAergic neurons play a significant role in the formation of stable antiphase outputs from the MSDB to the hippocampus.

  9. Activation/modulation of adaptive immunity emerges simultaneously after 17DD yellow fever first-time vaccination: is this the key to prevent severe adverse reactions following immunization?

    PubMed Central

    Martins, M Â; Silva, M L; Marciano, A P V; Peruhype-Magalhães, V; Eloi-Santos, S M; Ribeiro, J G L; Correa-Oliveira, R; Homma, A; Kroon, E G; Teixeira-Carvalho, A; Martins-Filho, O A

    2007-01-01

    Over past decades the 17DD yellow fever vaccine has proved to be effective in controlling yellow fever and promises to be a vaccine vector for other diseases, but the cellular and molecular mechanisms by which it elicits such broad-based immunity are still unclear. In this study we describe a detailed phenotypic investigation of major and minor peripheral blood lymphocyte subpopulations aimed at characterizing the kinetics of the adaptive immune response following primary 17DD vaccination. Our major finding is a decreased frequency of circulating CD19+ cells at day 7 followed by emerging activation/modulation phenotypic features (CD19+interleukin(IL)10R+/CD19+CD32+) at day 15. Increased frequency of CD4+human leucocyte antigen D-related(HLA-DR+) at day 7 and CD8+HLA-DR+ at day 30 suggest distinct kinetics of T cell activation, with CD4+ T cells being activated early and CD8+ T cells representing a later event following 17DD vaccination. Up-regulation of modulatory features on CD4+ and CD8+ cells at day 15 seems to be the key event leading to lower frequency of CD38+ T cells at day 30. Taken together, our findings demonstrate the co-existence of phenotypic features associated with activation events and modulatory pathways. Positive correlations between CD4+HLA-DR+ cells and CD4+CD25high regulatory T cells and the association between the type 0 chemokine receptor CCR2 and the activation status of CD4+ and CD8+ cells further support this hypothesis. We hypothesize that this controlled microenviroment seems to be the key to prevent the development of serious adverse events, and even deaths, associated with the 17DD vaccine reported in the literature. PMID:17309541

  10. Post-Knowledge of Results Delay: Effects of Interpolated Activity on Learning and Performance.

    ERIC Educational Resources Information Center

    Benedetti, Carol; McCullagh, Penny

    1987-01-01

    Experimental evidence strongly supports the assumption that knowledge of results (KR) is necessary for learning to occur. This study compares the effects of KR or no-KR with the effects of an interpolated verbal activity on learning and performance of a timed motor task. Results are presented. (Author/MT)

  11. We Are What We Eat! But Who Controls Our Choice? An Active Learning Project on Food & Nutrition with Activities for Key Stages 1, 2, 3, and 4.

    ERIC Educational Resources Information Center

    Jarvis, Heather

    This activity book is designed to create awareness about all the issues attached to food supply and a healthy diet with factual information. Materials are provided for teachers to teach children about food in its entirety. The nine units include: (1) "Starting Activities: Sorting Foods and Factors Which Control Our Diet"; (2) "Food Likes and…

  12. Key Results of Interaction Models with Centering

    ERIC Educational Resources Information Center

    Afshartous, David; Preston, Richard A.

    2011-01-01

    We consider the effect on estimation of simultaneous variable centering and interaction effects in linear regression. We technically define, review, and amplify many of the statistical issues for interaction models with centering in order to create a useful and compact reference for teachers, students, and applied researchers. In addition, we…

  13. ADAM12 redistributes and activates MMP-14, resulting in gelatin degradation, reduced apoptosis and increased tumor growth.

    PubMed

    Albrechtsen, Reidar; Kveiborg, Marie; Stautz, Dorte; Vikeså, Jonas; Noer, Julie B; Kotzsh, Alexander; Nielsen, Finn Cilius; Wewer, Ulla M; Fröhlich, Camilla

    2013-10-15

    Matrix metalloproteinases (MMPs), in particular MMP-2, MMP-9 and MMP-14, play a key role in various aspects of cancer pathology. Likewise, ADAMs (a disintegrin and metalloproteinases), including ADAM12, are upregulated in malignant tumors and contribute to the pathology of cancers. Here, we show that there is a positive correlation between MMP-14 and ADAM12 expression in human breast cancer. We demonstrated that in 293-VnR and human breast cancer cells expressing ADAM12 at the cell surface, endogenous MMP-14 was recruited to the cell surface, resulting in its activation. Subsequent to this activation, gelatin degradation was stimulated and tumor cell apoptosis was decreased, with reduced expression of the pro-apoptotic proteins BCL2L11 and BIK. The effect on gelatin degradation was abrogated by inhibition of the MMP-14 activity and appeared to be dependent on cell surface αVβ3 integrin localization, but neither the catalytic activity of ADAM12 nor the cytoplasmic tail of ADAM12 were required. The significance of ADAM12-induced activation of MMP-14 was underscored by a reduction in MMP-14-mediated gelatin degradation and abolition of apoptosis-protective effects by specific monoclonal antibodies against ADAM12. Furthermore, orthotopic implantation of ADAM12-expressing MCF7 cells in nude mice produced tumors with increased levels of activated MMP-14 and confirmed that ADAM12 protects tumor cells against apoptosis, leading to increased tumor progression. In conclusion, our data suggest that a ternary protein complex composed of ADAM12, αVβ3 integrin and MMP-14 at the tumor cell surface regulates the function of MMP-14. This interaction might point to a novel concept for the development of MMP-14-targeting drugs in treating cancer.

  14. Plasticity of hypothalamic dopamine neurons during lactation results in dissociation of electrical activity and release.

    PubMed

    Romanò, Nicola; Yip, Siew H; Hodson, David J; Guillou, Anne; Parnaudeau, Sébastien; Kirk, Siobhan; Tronche, François; Bonnefont, Xavier; Le Tissier, Paul; Bunn, Stephen J; Grattan, Dave R; Mollard, Patrice; Martin, Agnès O

    2013-03-06

    Tuberoinfundibular dopamine (TIDA) neurons are the central regulators of prolactin (PRL) secretion. Their extensive functional plasticity allows a change from low PRL secretion in the non-pregnant state to the condition of hyperprolactinemia that characterizes lactation. To allow this rise in PRL, TIDA neurons are thought to become unresponsive to PRL at lactation and functionally silenced. Here we show that, contrary to expectations, the electrical properties of the system were not modified during lactation and that the neurons remained electrically responsive to a PRL stimulus, with PRL inducing an acute increase in their firing rate during lactation that was identical to that seen in non-pregnant mice. Furthermore, we show a long-term organization of TIDA neuron electrical activity with an harmonization of their firing rates, which remains intact during lactation. However, PRL-induced secretion of dopamine (DA) at the median eminence was strongly blunted during lactation, at least in part attributable to lack of phosphorylation of tyrosine hydroxylase, the key enzyme involved in DA synthesis. We therefore conclude that lactation, rather than involving electrical silencing of TIDA neurons, represents a condition of decoupling between electrical activity at the cell body and DA secretion at the median eminence.

  15. Electrocardiograhic findings resulting in inappropriate cardiac catheterization laboratory activation for ST-segment elevation myocardial infarction

    PubMed Central

    Shamim, Shariq; McCrary, Justin; Wayne, Lori; Gratton, Matthew

    2014-01-01

    Background Prompt reperfusion has been shown to improve outcomes in patients with acute ST-segment elevation myocardial infarction (STEMI) with a goal of culprit vessel patency in <90 minutes. This requires a coordinated approach between the emergency medical services (EMS), emergency department (ED) and interventional cardiology. The urgency of this process can contribute to inappropriate cardiac catheterization laboratory (CCL) activations. Objectives One of the major determinants of inappropriate activations has been misinterpretation of the electrocardiogram (ECG) in the patient with acute chest pain. Methods We report the ECG findings for all CCL activations over an 18-month period after the inception of a STEMI program at our institution. Results There were a total of 139 activations with 77 having a STEMI diagnosis confirmed and 62 activations where there was no STEMI. The inappropriate activations resulted from a combination of atypical symptoms and misinterpretation of the ECG (45% due to anterior ST-segment elevation) on patient presentation. The electrocardiographic abnormalities were particularly problematic in African-Americans with left ventricular hypertrophy. Conclusions In this single-center, prospective observational study, nearly half of the inappropriate STEMI activations were due to the misinterpretation of anterior ST-segment elevation and this finding was commonly seen in African-Americans with left ventricular hypertrophy. PMID:25009790

  16. The Supernova Key Project

    NASA Astrophysics Data System (ADS)

    Howell, Dale Andrew

    2017-01-01

    Las Cumbres Observatory is a global network of robotic telescopes specializing in time domain astronomy. It currently has nine 1m telescopes, two 2m telescopes, and seven 0.4m telescopes. The Supernova Key Project is a 3 year program to obtain light curves and spectra of 500 supernovae with Las Cumbres Observatory. Here we show recent results, detail plans for the next Supernova Key Project, and explain how the US community can get involved.

  17. T cells, osteoblasts, and osteocytes: interacting lineages key for the bone anabolic and catabolic activities of parathyroid hormone.

    PubMed

    Pacifici, Roberto

    2016-01-01

    Osteoimmunology is a field of research dedicated to the study of the interactions between the immune system and bone. Among the cells of the immune system that regulate bone turnover and the responsiveness of bone cells to calciothropic hormones are bone marrow T lymphocytes. T cells secrete osteoclastogenic cytokines such as RANKL and TNF-α, as well as factors that stimulate bone formation, one of which is Wnt10b. In addition, T cells regulate the differentiation and life span of stromal cells (SCs) and their responsiveness to parathyroid hormone (PTH) via costimulatory molecules expressed on their surface. The conditioning effect of T cells on SCs is inherited by the osteoblastic and osteocytic progeny of SCs. As a result, osteoblastic cells of T cell-deficient mice have functional characteristics different from corresponding cells of T cell-replete mice. These differences include the ratio of RANKL/OPG produced in response to continuous PTH treatment, and the osteoblastogenic response to intermittent PTH treatment. This article reviews the evidence indicating that the effects of PTH are mediated not only by osteoblasts and osteocytes but also by T cells.

  18. T cells, osteoblasts, and osteocytes: interacting lineages key for the bone anabolic and catabolic activities of parathyroid hormone

    PubMed Central

    Pacifici, Roberto

    2015-01-01

    Osteoimmunology is field of research dedicated to the study of the interactions between the immune system and bone. Among the cells of the immune system that regulate bone turnover and the responsiveness of bone cells to calciothropic hormones are bone marrow T lymphocytes. T cells secrete osteoclastogenic cytokines such as RANKL and TNF-α, as well as factors that stimulate bone formation, one of which is Wnt10b. In addition, T cells regulate the differentiation and life span of stromal cells and their responsiveness to parathyroid hormone (PTH) via costimulatory molecules expressed on their surface. The conditioning effect of T cells on stromal cells (SCs) is inherited by the osteoblastic and osteocytic progeny of SCs. As a result, osteoblastic cells of T cell–deficient mice have functional characteristics different from corresponding cells of T cell–replete mice. These differences include the ratio of RANKL/OPG produced in response to continuous PTH treatment, and the osteoblastogenic response to intermittent PTH treatment. This article reviews the evidence indicating that the effects of parathyroid hormone are mediated not only by osteoblasts and osteocytes but also by T cells. PMID:26662934

  19. Quantitative Proteomic analysis on Activated Hepatic Stellate Cells reversion Reveal STAT1 as a key regulator between Liver Fibrosis and recovery

    PubMed Central

    Zhang, Hongyu; Chen, Fangyan; Fan, Xu; Lin, Cong; Hao, Yunwei; Wei, Handong; Lin, Weiran; Jiang, Ying; He, Fuchu

    2017-01-01

    Understanding the changes of activated HSCs reversion is an essential step toward clarifying the potential roles of HSCs in the treatment of liver fibrosis. In this study, we chose adipocyte differentiation mixture to induce LX-2 cells for 2 days in vitro as reversion phase, comparing with normal cultured LX-2 cells as activation phase. Mass spectrometric-based SILAC technology was adopted to study differentially expressed proteome of LX-2 cells between reversion and activation. Compared with activated HSCs, 273 proteins showed significant differences in reverted HSCs. The main pathway of up-regulated proteins associated with reversion of HSCs mainly related to oxidation-reduction and lipid metabolism, while the top pathway of down-regulated proteins was found in regulated cytoskeleton formation. Changes in the expression levels of selected proteins were verified by Western blotting analysis, especially STAT1, FLNA, LASP1, and NAMPT proteins. The distinct roles of STAT1 were further analyzed between activated and reverted of HSCs, it was found that STAT1 could affect cell proliferation of HSCs and could be viewed as a key regulator in the reversion of HSCs. Thus, the proteomic analysis could accelerate our understanding of the mechanisms of HSC reversion on cessation of fibrogenic stimuli and provide new targets for antifibrotic liver therapy. PMID:28322315

  20. Progress, opportunities, and key fields for groundwater quality research under the impacts of human activities in China with a special focus on western China.

    PubMed

    Li, Peiyue; Tian, Rui; Xue, Chenyang; Wu, Jianhua

    2017-03-10

    Groundwater quality research is extremely important for supporting the safety of the water supply and human health in arid and semi-arid areas of China. This review article was constructed to report the latest research progress of groundwater quality in western China where groundwater quality is undergoing fast deterioration because of fast economic development and extensive anthropogenic activities. The opportunities brought by increasing public awareness of groundwater quality protection were also highlighted and discussed. To guide and promote further development of groundwater quality research in China, especially in western China, ten key groundwater quality research fields were proposed. The review shows that the intensification of human activities and the associated impacts on groundwater quality in China, especially in western China, has made groundwater quality research increasingly important, and has caught the attention of local, national, and international agencies and scholars. China has achieved some progress in groundwater quality research in terms of national and regional laws, regulations, and financial supports. The future of groundwater quality research in China, especially in western China, is promising reflected by the opportunities highlighted. The key research fields proposed in this article may also inform groundwater quality protection and management at the national and international level.

  1. Zymogen activation confers thermodynamic stability on a key peptide bond and protects human cationic trypsin from degradation.

    PubMed

    Szabó, András; Radisky, Evette S; Sahin-Tóth, Miklós

    2014-02-21

    Human cationic trypsinogen, precursor of the digestive enzyme trypsin, can be rapidly degraded to protect the pancreas when pathological conditions threaten, while trypsin itself is impressively resistant to degradation. For either form, degradation is controlled by two necessary initial proteolytic events: cleavage of the Leu81-Glu82 peptide bond by chymotrypsin C (CTRC) and cleavage of the Arg122-Val123 peptide bond by trypsin. Here we demonstrate that the Leu81-Glu82 peptide bond of human cationic trypsin, but not trypsinogen, is thermodynamically stable, such that cleavage by CTRC leads to an equilibrium mixture containing 10% cleaved and 90% uncleaved trypsin. When cleaved trypsin was incubated with CTRC, the Leu81-Glu82 peptide bond was re-synthesized to establish the same equilibrium. The thermodynamic stability of the scissile peptide bond was not dependent on CTRC or Leu-81, as re-synthesis was also accomplished by other proteases acting on mutated cationic trypsin. The Leu81-Glu82 peptide bond is located within a calcium binding loop, and thermodynamic stability of the bond was strictly dependent on calcium and on the calcium-coordinated residue Glu-85. Trypsinolytic cleavage of the Arg122-Val123 site was also delayed in trypsin relative to trypsinogen in a calcium-dependent manner, but for this bond cleavage was modulated by kinetic rather than thermodynamic control. Our results reveal that the trypsinogen to trypsin conformational switch modulates cleavage susceptibility of nick sites by altering both the thermodynamics and kinetics of cleavage to protect human cationic trypsin from premature degradation.

  2. Efficacy of physical activity in the adjunctive treatment of major depressive disorders: preliminary results

    PubMed Central

    2007-01-01

    Background No controlled trials have evaluated the long term efficacy of exercise activity to improve the treatment of patients with Major Depressive Disorders. The aim of the present study was to confirm the efficacy of the adjunctive physical activity in the treatment of major depressive disorders, with a long term follow up (8 months). Methods Trial with randomized naturalistic control. Patients selected from the clinical activity registries of the Psychiatric Unit of the University of Cagliari, Italy. Inclusion criteria: female, between 40 and 60 years, diagnosis of Major Depressive Disorders (DSM-IV TR) resistant to the ongoing treatment. Exclusion criteria: diagnosis of psychotic disorders; any contraindications to physical activity. 30 patients (71.4% of the eligible) participated to the study. Cases: 10 randomized patients undergoing pharmacological treatment plus physical activity. Controls: 20 patients undergoing only pharmacological therapy. The following tools were collected from each patient by two different psychiatric physicians at baseline and 8 month after the beginning of exercise program: SCID-I, HAM-D, CGI (Clinical Global Impression), GAF. Results The patients that made physical activity had their HAM-D, GAF and CGI score improved from T0 to T8, all differences were statistically significant. In the control group HAM-D, GAF and CGI scores do not show any statistically significant differences between T0 and T8. Limits Small sample size limited to female in adult age; control group was not subject to any structured rehabilitation activity or placebo so it was impossible to evaluate if the improvement was due to a non specific therapeutic effect associated with taking part in a social activity. Conclusion Physical activity seems a good adjunctive treatment in the long term management of patients with MDD. Randomized placebo controlled trials are needed to confirm the results. PMID:17620123

  3. aPKC Phosphorylation of HDAC6 Results in Increased Deacetylation Activity

    PubMed Central

    Du, Yifeng; Seibenhener, Michael L.; Yan, Jin; Jiang, Jianxiong; Wooten, Michael C.

    2015-01-01

    The Class II histone deacetylase, HDAC6, has been shown to be involved in cell motility, aggresome formation and mitochondria transport. HDAC6 deacetylase activity regulates α-tubulin acetylation levels and thus plays a critical role in these processes. In turn, HDAC6 activity can be regulated by interaction with various proteins including multiple kinases. Kinase mediated phosphorylation of HDAC6 can lead to either increased or reduced activity. Our previous research has shown that sequestosome1/p62 (SQSTM1/p62) interacts with HDAC6 and regulates its activity. As SQSTM1/p62 is a scaffolding protein known to interact directly with the zeta isoform of Protein Kinase C (PKCζ), we sought to examine if HDAC6 could be a substrate for PKCζ phosphorylation and if so, how its activity might be regulated. Our data demonstrate that HDAC6 is not only present in a protein complex with PKCζ but can also be phosphorylated by PKCζ. We also show that specific phosphorylation of HDAC6 by PKCζ increases HDAC6 deacetylase activity resulting in reduced acetylated tubulin levels. Our findings provide novel insight into the molecular mechanism by which HDAC6, PKCζ and SQSTM1/p62 function together in protein aggregate clearance. These results also highlight a new research direction which may prove fruitful for understanding the underlying cause of several neurodegenerative diseases. PMID:25860570

  4. aPKC phosphorylation of HDAC6 results in increased deacetylation activity.

    PubMed

    Du, Yifeng; Seibenhener, Michael L; Yan, Jin; Jiang, Jianxiong; Wooten, Michael C

    2015-01-01

    The Class II histone deacetylase, HDAC6, has been shown to be involved in cell motility, aggresome formation and mitochondria transport. HDAC6 deacetylase activity regulates α-tubulin acetylation levels and thus plays a critical role in these processes. In turn, HDAC6 activity can be regulated by interaction with various proteins including multiple kinases. Kinase mediated phosphorylation of HDAC6 can lead to either increased or reduced activity. Our previous research has shown that sequestosome1/p62 (SQSTM1/p62) interacts with HDAC6 and regulates its activity. As SQSTM1/p62 is a scaffolding protein known to interact directly with the zeta isoform of Protein Kinase C (PKCζ), we sought to examine if HDAC6 could be a substrate for PKCζ phosphorylation and if so, how its activity might be regulated. Our data demonstrate that HDAC6 is not only present in a protein complex with PKCζ but can also be phosphorylated by PKCζ. We also show that specific phosphorylation of HDAC6 by PKCζ increases HDAC6 deacetylase activity resulting in reduced acetylated tubulin levels. Our findings provide novel insight into the molecular mechanism by which HDAC6, PKCζ and SQSTM1/p62 function together in protein aggregate clearance. These results also highlight a new research direction which may prove fruitful for understanding the underlying cause of several neurodegenerative diseases.

  5. Return to sporting activity after Birmingham hip resurfacing arthroplasty: Mid term results

    PubMed Central

    Sandiford, Nemandra; Muirhead-Allwood, SK; Skinner, JA

    2015-01-01

    Background: Hip resurfacing arthroplasty (HRA) is primarily indicated for young, active patients with disabling coxarthrosis who wish to remain active and return to sports after surgery. Relatively few prospective studies have assessed return to sporting activity and impact of gender and age on this. Materials and Methods: Seventy-nine consecutive patients treated with HRA were included. Patients were reviewed clinically and radiologically. Function was assessed using the modified University of California Los Angeles (UCLA) activity score. The Oxford, Harris and WOMAC hip scores were calculated. Results: Average age at the time of surgery was 54.9 years (range 34.5–73.6 years). Average preoperative and postoperative UCLA scores were 4 and 7.6 respectively. Patients were involved in 2 (0–4) sporting activities preoperatively and 2 (0–5) postoperatively. Preoperative and postoperative Oxford Hip Scores, Harris Hip Score and WOMAC scores were 40, 46 and 51 and 16, 94 and 3 respectively (P < 0.0001). Patients returned to sports at an average of 3 months postoperatively. Conclusion: Patients were able to return to sports by 3 months and perform the same number of activities at preoperative intensity. Activity levels are maintained up to the medium term with few complications. PMID:26806965

  6. CHP REGIONAL APPLICATION CENTERS: A PRELIMINARY INVENTORY OF ACTIVITIES AND SELECTED RESULTS

    SciTech Connect

    Schweitzer, Martin

    2009-10-01

    Eight Regional CHP Application Centers (RACs) are funded by the U.S. Department of Energy (DOE) to facilitate the development and deployment of Combined Heat and Power (CHP) technologies in all 50 states. The RACs build end-user awareness by providing CHP-related information to targeted markets through education and outreach; they work with the states and regulators to encourage the creation and adoption of favorable public policies; and they provide CHP users and prospective users with technical assistance and support on specific projects. The RACs were started by DOE as a pilot program in 2001 to support the National CHP Roadmap developed by industry to accelerate deployment of energy efficient CHP technologies (U.S. Combined Heat and Power Association 2001). The intent was to foster a regional presence to build market awareness, address policy issues, and facilitate project development. Oak Ridge National Laboratory (ORNL) has supported DOE with the RAC program since its inception. In 2007, ORNL led a cooperative effort involving DOE and some CHP industry stakeholders to establish quantitative metrics for measuring the RACs accomplishments. This effort incorporated the use of logic models to define and describe key RAC activities, outputs, and outcomes. Based on this detailed examination of RAC operations, potential metrics were identified associated with the various key sectors addressed by the RACs: policy makers; regulatory agencies; investor owned utilities; municipal and cooperative utilities; financiers; developers; and end users. The final product was reviewed by a panel of representatives from DOE, ORNL, RACs, and the private sector. The metrics developed through this effort focus on major RAC activities as well as on CHP installations and related outcomes. All eight RACs were contacted in August 2008 and asked to provide data for every year of Center operations for those metrics on which they kept records. In addition, data on CHP installations and

  7. Zinc-finger protein 91 plays a key role in LIGHT-induced activation of non-canonical NF-{kappa}B pathway

    SciTech Connect

    Jin, Hong Ri; Jin, Xuejun; Lee, Jung Joon

    2010-10-01

    Research highlights: {yields} LIGHT induces ZFP91expression and nuclear translocation of p65, p52, and RelB in LT{beta}R signaling. {yields} ZFP91 knock-down abolishes DNA-binding activity of p52 and RelB but not of p65. {yields} ZFP91 regulates LIGHT-induced stabilization and activation of NIK. {yields} ZFP91 is required for the expression of non-canonical NF-{kappa}B target genes. -- Abstract: LIGHT is a member of tumor necrosis factor (TNF) superfamily, and its function is mediated through lymphotoxin-{beta} receptor (LT{beta}R), which is known to play important roles in inflammatory and immune responses through activation of NF-{kappa}B signaling pathways. However, molecular mechanism of LT{beta}R ligation-induced NF-{kappa}B signaling remains incompletely understood. In this report we demonstrate that a novel zinc-finger protein 91 (ZFP91) is a critical regulator in LIGHT-induced activation of non-canonical NF-{kappa}B pathway. ZFP91 appears to be required for NF-{kappa}B2 (p100) processing to p52, nuclear translocation of p52 and RelB, and DNA-binding activity of NF-{kappa}B in LIGHT-induced activation of non-canonical NF-{kappa}B pathway. Furthermore, ZFP91 knock-down by RNA interference blocks the LIGHT-induced accumulation of NIK and p100 processing, as well as the expression of non-canonical NF-{kappa}B target genes. These data clearly indicate that ZFP91 is a key regulator in LIGHT-induced activation of non-canonical NF-{kappa}B pathway in LT{beta}R signaling.

  8. Status of data, major results, and plans for geophysical activities, Yucca Mountain Project

    SciTech Connect

    Oliver, H.W.; Hardin, E.L.; Nelson, P.H.

    1990-07-01

    This report describes past and planned geophysical activities associated with the Yucca Mountain Project and is intended to serve as a starting point for integration of geophysical activities. This report relates past results to site characterization plans, as presented in the Yucca Mountain Site Characterization Plan (SCP). This report discusses seismic exploration, potential field methods, geoelectrical methods, teleseismic data collection and velocity structural modeling, and remote sensing. This report discusses surface-based, airborne, borehole, surface-to-borehole, crosshole, and Exploratory Shaft Facility-related activities. The data described in this paper, and the publications discussed, have been selected based on several considerations; location with respect to Yucca Mountain, whether the success or failure of geophysical data is important to future activities, elucidation of features of interest, and judgment as to the likelihood that the method will produce information that is important for site characterization. 65 refs., 19 figs., 12 tabs.

  9. Changes in breath trihalomethane levels resulting from household water-use activities.

    PubMed

    Gordon, Sydney M; Brinkman, Marielle C; Ashley, David L; Blount, Benjamin C; Lyu, Christopher; Masters, John; Singer, Philip C

    2006-04-01

    Common household water-use activities such as showering, bathing, drinking, and washing clothes or dishes are potentially important contributors to individual exposure to trihalomethanes (THMs), the major class of disinfection by-products of water treated with chlorine. Previous studies have focused on showering or bathing activities. In this study, we selected 12 common water-use activities and determined which may lead to the greatest THM exposures and result in the greatest increase in the internal dose. Seven subjects performed the various water-use activities in two residences served by water utilities with relatively high and moderate total THM levels. To maintain a consistent exposure environment, the activities, exposure times, air exchange rates, water flows, water temperatures, and extraneous THM emissions to the indoor air were carefully controlled. Water, indoor air, blood, and exhaled-breath samples were collected during each exposure session for each activity, in accordance with a strict, well-defined protocol. Although showering (for 10 min) and bathing (for 14 min), as well as machine washing of clothes and opening mechanical dishwashers at the end of the cycle, resulted in substantial increases in indoor air chloroform concentrations, only showering and bathing caused significant increases in the breath chloroform levels. In the case of bromodichloromethane (BDCM), only bathing yielded a significantly higher air level in relation to the preexposure concentration. For chloroform from showering, strong correlations were observed for indoor air and exhaled breath, blood and exhaled breath, indoor air and blood, and tap water and blood. Only water and breath, and blood and breath were significantly associated for chloroform from bathing. For BDCM, significant correlations were obtained for blood and air, and blood and water from showering. Neither dibromochloromethane nor bromoform gave measurable breath concentrations for any of the activities

  10. Control of a Shunt Active Power Filter with Neural Networks—Theory and Practical Results

    NASA Astrophysics Data System (ADS)

    Villalva, Marcelo G.; Filho, Ernesto Ruppert

    This paper presents theoretical studies and practical results obtained with a four-wire shunt active power filter fully controlled with neural networks. The paper is focused on a current compensation method based on adaptive linear elements (adalines), which are powerful and easy-to-use neural networks. The reader will find here an introduction about these networks, an explanatory section about the achievement of Fourier series with adalines, and the full description of an adaline-based selective current compensator. The paper also brings a quick discussion about the use of a feedforward neural network in the current controller of the active filter, as well as simulation and experimental results obtained with the prototype of an active power filter.

  11. RIP1 kinase activity is dispensable for normal development but is a key regulator of inflammation in SHARPIN-deficient mice

    PubMed Central

    Berger, Scott B.; Kasparcova, Viera; Hoffman, Sandy; Swift, Barb; Dare, Lauren; Schaeffer, Michelle; Capriotti, Carol; Cook, Michael; Finger, Joshua; Hughes-Earle, Angela; Harris, Philip A.; Kaiser, William J.; Mocarski, Edward S.; Bertin, John; Gough, Peter J.

    2014-01-01

    RIP1 kinase is a key regulator of TNF-induced NFκB activation, apoptosis and necroptosis through its kinase and scaffolding activities. Dissecting the balance of RIP1 kinase activity and scaffolding function in vivo during development and TNF-dependent inflammation has been hampered by the perinatal lethality of RIP1-deficient mice. Here we generated RIP1 kinase-dead (Ripk1K45A) mice and showed they are viable and healthy, indicating that kinase activity of RIP1, but not its scaffolding function, is dispensable for viability and homeostasis. After validating that the Ripk1K45A mice were specifically protected against necroptotic stimuli in vitro and in vivo, we crossed these mice to SHARPIN-deficient cpdm mice, which develop severe skin and multi-organ inflammation that has been hypothesized to be mediated by TNF-dependent apoptosis and/or necroptosis. Remarkably, crossing Ripk1K45A mice to the cpdm strain protected against all cpdm-related pathology. Together, these data suggest that RIP1 kinase represents an attractive therapeutic target for TNF-driven inflammatory diseases. PMID:24821972

  12. Building Technologies Program Key Activities

    SciTech Connect

    2011-12-15

    The Building Technologies Program (BTP) employs a balanced approach to making buildings more energy efficient. The three pillars of our program, research and development (R&D), market stimulation, and building and equipment standards, help meet our strategic vision.

  13. [The results of the introduction of a protocol of preventive activities in a primary care center].

    PubMed

    Tamayo Marco, B; Deniel Rosanas, J; López Plana, A; Trallero Fort, J C; Lafuente Navarro, A; Lafuente Navarro, C

    1991-04-01

    A sample of 360 people was analyzed. They had received the protocol of preventive activities of the "Unitat Docent de Medicina Familiar i Comunitària de Barcelona" during 1989. The results of those activities directed to the prevention of cardiovascular risk and to the detection of excessive alcohol intake are reported, as they are those with the easiest and widest implementation. Overall results include hypercholesterolemia in 43.9%, abnormal blood pressure in 10.5%, a rate of smokers of 31.7%, 7.7% with an excessive alcohol intake, and 51.9% of obese individuals. The results are also shown by age and sex groups. In the discussion, the results are compared with those expected for our population. It is concluded that preventive measures should be encouraged by primary health are teams.

  14. "Exercise Dependence"--A Problem or Natural Result of High Activity?

    ERIC Educational Resources Information Center

    Phelan, Suzanne; Bond, Dale S.; Lang, Wei; Jordan, Dustin; Wing, Rena R.

    2011-01-01

    Objectives: To compare physical activity (PA) and exercise dependence (ED) in 267 weight-loss maintainers (WLM) and 213 normal-weight (NW) controls. Methods: PA and ED assessed via accelerometery and the Exercise Dependence Questionnaire. Results: WLM had higher PA levels and ED scores than those of NW (P less than 0.0001). WLM status (P = 0.006)…

  15. Dynamic Docking Test System (DDTS) active table frequency response test results. [Apollo Soyuz Test Project

    NASA Technical Reports Server (NTRS)

    Gates, R. M.

    1974-01-01

    Results are presented of the frequency response test performed on the dynamic docking test system (DDTS) active table. Sinusoidal displacement commands were applied to the table and the dynamic response determined from measured actuator responses and accelerometers mounted to the table and one actuator.

  16. Social Work Roles and Activities Regarding Psychiatric Medication: Results of a National Survey

    ERIC Educational Resources Information Center

    Bentley, Kia J.; Walsh, Joseph; Farmer, Rosemary L.

    2005-01-01

    This article reports the findings of a 2001 national survey of social workers regarding their everyday practice roles and activities regarding psychiatric medication. The results of this quantitative study indicate variability in the types of roles carried out by social workers with regard to psychiatric medication, but that perceptions of…

  17. Prolactin increases the synthesis of 7alpha-hydroxypregnenolone, a key factor for induction of locomotor activity, in breeding male Newts.

    PubMed

    Haraguchi, Shogo; Koyama, Teppei; Hasunuma, Itaru; Vaudry, Hubert; Tsutsui, Kazuyoshi

    2010-05-01

    We recently found that the Japanese red-bellied newt, Cynops pyrrhogaster, actively produces 7alpha-hydroxypregnenolone, a previously undescribed amphibian neurosteroid. 7alpha-Hydroxypregnenolone stimulates locomotor activity of male newts. Locomotor activity of male newts increases during the breeding period as in other wild animals, but the molecular mechanism for such a change in locomotor activity is poorly understood. Here we show that the adenohypophyseal hormone prolactin (PRL) stimulates 7alpha-hydroxypregnenolone synthesis in the brain, thus increasing locomotor activity of breeding male newts. In this study, cytochrome P450(7alpha) (CYP7B), a steroidogenic enzyme catalyzing the formation of 7alpha-hydroxypregnenolone, was first identified to analyze seasonal changes in 7alpha-hydroxypregnenolone synthesis. Only males exhibited marked seasonal changes in 7alpha-hydroxypregnenolone synthesis and CYP7B expression in the brain, with a maximum level in the spring breeding period when locomotor activity of males increases. Subsequently we identified PRL as a key component of the mechanism regulating 7alpha-hydroxypregnenolone synthesis. Hypophysectomy decreased 7alpha-hydroxypregnenolone synthesis in the male brain, whereas administration of PRL but not gonadotropins to hypophysectomized males caused a dose-dependent increase in 7alpha-hydroxypregnenolone synthesis. To analyze the mode of PRL action, CYP7B and the receptor for PRL were localized in the male brain. PRL receptor was expressed in the neurons expressing CYP7B in the magnocellular preoptic nucleus. Thus, PRL appears to act directly on neurosteroidogenic magnocellular preoptic nucleus neurons to regulate 7alpha-hydroxypregnenolone synthesis, thus inducing seasonal locomotor changes in male newts. This is the first report describing the regulation of neurosteroidogenesis in the brain by an adenohypophyseal hormone in any vertebrate.

  18. [Physical activity: results of the German Health Interview and Examination Survey for Adults (DEGS1)].

    PubMed

    Krug, S; Jordan, S; Mensink, G B M; Müters, S; Finger, J; Lampert, T

    2013-05-01

    Regular physical activity can have a positive effect on health at any age. Today's lifestyles, however, can often be characterised as sedentary. Therefore, the promotion of physical activity and sports has become an integral part of public health measures. The representative data of adults aged 18 to 79 years in Germany obtained from the "German Health Interview and Examination Survey for Adults" (DEGS1) provide an overview of self-estimated current physical activity behaviour. The results show that one third of the adult population claims to pay close attention to reaching a sufficient level of physical activity and one fourth participates in sports for at least 2 h/week on a regular basis. Thus, the percentage of adults regularly engaged in sports has increased compared to the previous "German National Health Interview and Examination Survey 1998". Still, four out of five adults do not achieve at least 2.5 h/week of moderate-intensity physical activity as recommended by the World Health Organisation. Consequently, future individual-level and population-level interventions should focus on target group-specific measures while continuing to promote regular physical activity in all segments of the population. An English full-text version of this article is available at SpringerLink as supplemental.

  19. Sequential activation of ground pads reduces skin heating during radiofrequency tumor ablation: in vivo porcine results.

    PubMed

    Schutt, David J; Swindle, M Michael; Helke, Kristi L; Bastarrika, Gorka; Schwarz, Florian; Haemmerich, Dieter

    2010-03-01

    Skin burns below ground pads during monopolar RF ablation are increasingly prevalent, thereby hindering the development of higher power RF generators capable of creating larger tumor ablation zones in combination with multiple or new applicators. Our goal was to evaluate reduction in skin temperatures via additional ground pads in an in vivo porcine model. Three ground pads placed on the animal's abdomen were activated either simultaneously or sequentially, where activation timing was adjusted to equilibrate skin temperature below each pad. Thirteen RF ablations (n = 4 simultaneous at 300 W, n = 5 sequential at 300 W, and n = 4 sequential at 375 W) were performed for 12 min via two internally cooled cluster electrodes placed in the gluteus maximus of domestic swine. Temperature rise at each pad and burn degree as determined via histology were compared. Ablation zone size was determined via T2-weighted MRI. Maximum temperature rise was significantly higher with simultaneous activation than with either of the sequential activation group (21.4 degrees C versus 8.1 degrees C or 9.6 degrees C, p < 0.01). Ablation zone diameters during simultaneous (300 W) and sequential activations (300 and 375 W) were and 6.9 +/- 0.3, 5.6 +/- 0.3, and 7.5 +/- 0.6 cm, respectively. Sequential activation of multiple ground pads results in significantly lower skin temperatures and less severe burns, as measured by histological examination.

  20. Modulation of fructokinase activity of potato (Solanum tuberosum) results in substantial shifts in tuber metabolism.

    PubMed

    Davies, Howard V; Shepherd, Louise V T; Burrell, Michael M; Carrari, Fernando; Urbanczyk-Wochniak, Ewa; Leisse, Andrea; Hancock, Robert D; Taylor, Mark; Viola, Roberto; Ross, Heather; McRae, Diane; Willmitzer, Lothar; Fernie, Alisdair R

    2005-07-01

    Potato plants (Solanum tuberosum L. cvs Desiree and Record) transformed with sense and antisense constructs of a cDNA encoding the potato fructokinase StFK1 exhibited altered transcription of this gene, altered amount of protein and altered enzyme activities. Measurement of the maximal catalytic activity of fructokinase revealed a 2-fold variation in leaf (from 90 to 180% of wild type activity) and either a 10- or 30-fold variation in tuber (from 10 or 30% to 300% in Record and Desiree, respectively) activity. The comparative effect of the antisense construct in leaf and tuber tissue suggests that this isoform is only a minor contributor to the total fructokinase activity in the leaf but the predominant isoform in the tuber. Antisense inhibition of the fructokinase resulted in a reduced tuber yield; however, its overexpression had no impact on this parameter. The modulation of fructokinase activity had few, consistent effects on carbohydrate levels, with the exception of a general increase in glucose content in the antisense lines, suggesting that this enzyme is not important for the control of starch synthesis. However, when metabolic fluxes were estimated, it became apparent that the transgenic lines display a marked shift in metabolism, with the rate of redistribution of radiolabel to sucrose markedly affected by the activity of fructokinase. These data suggest an important role for fructokinase, acting in concert with sucrose synthase, in maintaining a balance between sucrose synthesis and degradation by a mechanism independent of that controlled by the hexose phosphate-mediated activation of sucrose phosphate synthase.

  1. The International Prevalence Study on Physical Activity: results from 20 countries

    PubMed Central

    Bauman, Adrian; Bull, Fiona; Chey, Tien; Craig, Cora L; Ainsworth, Barbara E; Sallis, James F; Bowles, Heather R; Hagstromer, Maria; Sjostrom, Michael; Pratt, Michael

    2009-01-01

    Background Physical activity (PA) is one of the most important factors for improving population health, but no standardised systems exist for international surveillance. The International Physical Activity Questionnaire (IPAQ) was developed for international surveillance. The purpose of this study was a comparative international study of population physical activity prevalence across 20 countries. Methods Between 2002–2004, a standardised protocol using IPAQ was used to assess PA participation in 20 countries [total N = 52,746, aged 18–65 years]. The median survey response rate was 61%. Physical activity levels were categorised as "low", "moderate" and "high". Age-adjusted prevalence estimates are presented by sex. Results The prevalence of "high PA" varied from 21–63%; in eight countries high PA was reported for over half of the adult population. The prevalence of "low PA" varied from 9% to 43%. Males more frequently reported high PA than females in 17 of 20 countries. The prevalence of low PA ranged from 7–41% among males, and 6–49% among females. Gender differences were noted, especially for younger adults, with males more active than females in most countries. Markedly lower physical activity prevalence (10% difference) with increasing age was noted in 11 of 19 countries for males, but only in three countries for women. The ways populations accumulated PA differed, with some reporting mostly vigorous intensity activities and others mostly walking. Conclusion This study demonstrated the feasibility of international PA surveillance, and showed that IPAQ is an acceptable surveillance instrument, at least within countries. If assessment methods are used consistently over time, trend data will inform countries about the success of their efforts to promote physical activity. PMID:19335883

  2. Neural activity underlying tinnitus generation: results from PET and fMRI.

    PubMed

    Lanting, C P; de Kleine, E; van Dijk, P

    2009-09-01

    Tinnitus is the percept of sound that is not related to an acoustic source outside the body. For many forms of tinnitus, mechanisms in the central nervous system are believed to play an important role in the pathology. Specifically, three mechanisms have been proposed to underlie tinnitus: (1) changes in the level of spontaneous neural activity in the central auditory system, (2) changes in the temporal pattern of neural activity, and (3) reorganization of tonotopic maps. The neuroimaging methods fMRI and PET measure signals that presumably reflect the firing rates of multiple neurons and are assumed to be sensitive to changes in the level of neural activity. There are two basic paradigms that have been applied in functional neuroimaging of tinnitus. Firstly, sound-evoked responses as well as steady state neural activity have been measured to compare tinnitus patients to healthy controls. Secondly, paradigms that involve modulation of tinnitus by a controlled stimulus allow for a within-subject comparison that identifies neural activity that may be correlated to the tinnitus percept. Even though there are many differences across studies, the general trend emerging from the neuroimaging studies, is that tinnitus in humans may correspond to enhanced neural activity across several centers of the central auditory system. Also, neural activity in non-auditory areas including the frontal areas, the limbic system and the cerebellum seems associated with the perception of tinnitus. These results indicate that in addition to the auditory system, non-auditory systems may represent a neural correlate of tinnitus. Although the currently published neuroimaging studies typically show a correspondence between tinnitus and enhanced neural activity, it will be important to perform future studies on subject groups that are closely matched for characteristics such as age, gender and hearing loss in order to rule out the contribution of these factors to the abnormalities specifically

  3. Disability Weights for Chronic Mercury Intoxication Resulting from Gold Mining Activities: Results from an Online Pairwise Comparisons Survey

    PubMed Central

    Steckling, Nadine; Devleesschauwer, Brecht; Winkelnkemper, Julia; Fischer, Florian; Ericson, Bret; Krämer, Alexander; Hornberg, Claudia; Fuller, Richard; Plass, Dietrich; Bose-O’Reilly, Stephan

    2017-01-01

    In artisanal small-scale gold mining, mercury is used for gold-extraction, putting miners and nearby residents at risk of chronic metallic mercury vapor intoxication (CMMVI). Burden of disease (BoD) analyses allow the estimation of the public health relevance of CMMVI, but until now there have been no specific CMMVI disability weights (DWs). The objective is to derive DWs for moderate and severe CMMVI. Disease-specific and generic health state descriptions of 18 diseases were used in a pairwise comparison survey. Mercury and BoD experts were invited to participate in an online survey. Data were analyzed using probit regression. Local regression was used to make the DWs comparable to the Global Burden of Disease (GBD) study. Alternative survey (visual analogue scale) and data analyses approaches (linear interpolation) were evaluated in scenario analyses. A total of 105 participants completed the questionnaire. DWs for moderate and severe CMMVI were 0.368 (0.261–0.484) and 0.588 (0.193–0.907), respectively. Scenario analyses resulted in higher mean values. The results are limited by the sample size, group of interviewees, questionnaire extent, and lack of generally accepted health state descriptions. DWs were derived to improve the data basis of mercury-related BoD estimates, providing useful information for policy-making. Integration of the results into the GBD DWs enhances comparability. PMID:28075395

  4. Disability Weights for Chronic Mercury Intoxication Resulting from Gold Mining Activities: Results from an Online Pairwise Comparisons Survey.

    PubMed

    Steckling, Nadine; Devleesschauwer, Brecht; Winkelnkemper, Julia; Fischer, Florian; Ericson, Bret; Krämer, Alexander; Hornberg, Claudia; Fuller, Richard; Plass, Dietrich; Bose-O'Reilly, Stephan

    2017-01-10

    In artisanal small-scale gold mining, mercury is used for gold-extraction, putting miners and nearby residents at risk of chronic metallic mercury vapor intoxication (CMMVI). Burden of disease (BoD) analyses allow the estimation of the public health relevance of CMMVI, but until now there have been no specific CMMVI disability weights (DWs). The objective is to derive DWs for moderate and severe CMMVI. Disease-specific and generic health state descriptions of 18 diseases were used in a pairwise comparison survey. Mercury and BoD experts were invited to participate in an online survey. Data were analyzed using probit regression. Local regression was used to make the DWs comparable to the Global Burden of Disease (GBD) study. Alternative survey (visual analogue scale) and data analyses approaches (linear interpolation) were evaluated in scenario analyses. A total of 105 participants completed the questionnaire. DWs for moderate and severe CMMVI were 0.368 (0.261-0.484) and 0.588 (0.193-0.907), respectively. Scenario analyses resulted in higher mean values. The results are limited by the sample size, group of interviewees, questionnaire extent, and lack of generally accepted health state descriptions. DWs were derived to improve the data basis of mercury-related BoD estimates, providing useful information for policy-making. Integration of the results into the GBD DWs enhances comparability.

  5. Hemoglobin induced cell trauma indirectly influences endothelial TLR9 activity resulting in pulmonary vascular smooth muscle cell activation

    PubMed Central

    Loomis, Zoe; Eigenberger, Paul; Redinius, Katherine; Lisk, Christina; Karoor, Vijaya; Nozik-Grayck, Eva; Ferguson, Scott K.; Hassell, Kathryn; Nuss, Rachelle; Stenmark, Kurt; Buehler, Paul; Irwin, David C.

    2017-01-01

    It is now well established that both inherited and acquired forms of hemolytic disease can promote pulmonary vascular disease consequent of free hemoglobin (Hb) induced NO scavenging, elevations in reactive oxygen species and lipid peroxidation. It has recently been reported that oxidative stress can activate NFkB through a toll-like receptor 9 (TLR9) mediated pathway; further, TLR9 can be activated by either nuclear or mitochondrial DNA liberated by stress induced cellular trauma. We hypothesis that Hb induced lipid peroxidation and subsequent endothelial cell trauma is linked to TLR9 activation, resulting in IL-6 mediated pulmonary smooth muscle cell proliferation. We examined the effects of Hb on rat pulmonary artery endothelial and smooth muscle cells (rPAEC and rPASMC, respectively), and then utilized TLR9 and IL6 inhibitors, as well as the Hb and heme binding proteins (haptoglobin (Hp) and hemopexin (Hpx), respectively) to further elucidate the aforementioned mediators. Further, we explored the effects of Hb in vivo utilizing endothelial cell (EC) specific myeloid differentiation primary response gene-88 (MyD88) and TLR9 null mice. Our data show that oxidized Hb induces lipid peroxidation, cellular toxicity (5.5 ± 1.7 fold; p≤0.04), increased TLR9 activation (60%; p = 0.01), and up regulated IL6 expression (1.75±0.3 fold; p = 0.04) in rPAEC. Rat PASMC exhibited a more proliferative state (13 ± 1%; p = 0.01) when co-cultured with Hb activated rPAEC. These effects were attenuated with the sequestration of Hb or heme by Hp and Hpx as well as with TLR9 an IL-6 inhibition. Moreover, in both EC-MyD88 and TLR9 null mice Hb-infusion resulted in less lung IL-6 expression compared to WT cohorts. These results demonstrate that Hb-induced lipid peroxidation can initiate a modest TLR9 mediated inflammatory response, subsequently generating an activated SMC phenotype. PMID:28152051

  6. Phenolic compounds, antioxidant activity and in vitro inhibitory potential against key enzymes relevant for hyperglycemia and hypertension of commonly used medicinal plants, herbs and spices in Latin America.

    PubMed

    Ranilla, Lena Galvez; Kwon, Young-In; Apostolidis, Emmanouil; Shetty, Kalidas

    2010-06-01

    Traditionally used medicinal plants, herbs and spices in Latin America were investigated to determine their phenolic profiles, antioxidant activity and in vitro inhibitory potential against key enzymes relevant for hyperglycemia and hypertension. High phenolic and antioxidant activity-containing medicinal plants and spices such as Chancapiedra (Phyllantus niruri L.), Zarzaparrilla (Smilax officinalis), Yerba Mate (Ilex paraguayensis St-Hil), and Huacatay (Tagetes minuta) had the highest anti-hyperglycemia relevant in vitro alpha-glucosidase inhibitory activities with no effect on alpha-amylase. Molle (Schinus molle), Maca (Lepidium meyenii Walp), Caigua (Cyclanthera pedata) and ginger (Zingiber officinale) inhibited significantly the hypertension relevant angiotensin I-converting enzyme (ACE). All evaluated pepper (Capsicum) genus exhibited both anti-hyperglycemia and anti-hypertension potential. Major phenolic compounds in Matico (Piper angustifolium R.), Guascas (Galinsoga parviflora) and Huacatay were chlorogenic acid and hydroxycinnamic acid derivatives. Therefore, specific medicinal plants, herbs and spices from Latin America have potential for hyperglycemia and hypertension prevention associated with Type 2 diabetes.

  7. An unsuspected ecdysteroid/steroid phosphatase activity in the key T-cell regulator, Sts-1: surprising relationship to insect ecdysteroid phosphate phosphatase.

    PubMed

    Davies, Lyndsay; Anderson, Ian P; Turner, Philip C; Shirras, Alan D; Rees, Huw H; Rigden, Daniel J

    2007-05-15

    The insect enzyme ecdysteroid phosphate phosphatase (EPP) mobilizes active ecdysteroids from an inactive phosphorylated pool. Previously assigned to a novel class, it is shown here that it resides in the large histidine phosphatase superfamily related to cofactor-dependent phosphoglycerate mutase, a superfamily housing notably diverse catalytic activities. Molecular modeling reveals a plausible substrate-binding mode for EPP. Analysis of genomic and transcript data for a number of insect species shows that EPP may exist in both the single domain form previously characterized and in a longer, multidomain form. This latter form bears a quite unexpected relationship in sequence and domain architecture to vertebrate proteins, including Sts-1, characterized as a key regulator of T-cell activity. Long form Drosophila melanogaster EPP, human Sts-1, and a related protein from Caenorhabditis elegans have all been cloned, assayed, and shown to catalyse the hydrolysis of ecdysteroid and steroid phosphates. The surprising relationship described and explored here between EPP and Sts-1 has implications for our understanding of the function(s) of both.

  8. Epidermal Platelet-activating Factor Receptor Activation and Ultraviolet B Radiation Result in Synergistic Tumor Necrosis Factor-alpha Production

    PubMed Central

    Wolverton, Jay E.; Al-Hassani, Mohammed; Yao, Yongxue; Zhang, Qiwei; Travers, Jeffrey B.

    2010-01-01

    Ultraviolet B radiation (UVB) is a potent stimulator of epidermal cytokine production which has been implicated in photoaggravated dermatoses. In addition to cytokines such as tumor necrosis factor-α (TNF-α), UVB generates bioactive lipids including platelet-activating factor (PAF). Our previous studies have demonstrated that UVB-mediated production of keratinocyte TNF-α is in part due to PAF. The current studies use a human PAF-receptor (PAF-R) negative epithelial cell line transduced with PAF-Rs and PAF–R-deficient mice to demonstrate that activation of the epidermal PAF-R along with UVB irradiation results in a synergistic production of TNF-α. It should be noted that PAF-R effects are mimicked by the protein kinase C (PKC) agonist phorbol myristic acetate, and are inhibited by pharmacological antagonists of the PKC gamma isoenzyme. These studies suggest that concomitant PAF-R activation and UVB irradiation results in a synergistic production of the cytokine TNF-α which is mediated in part via PKC. These studies provide a novel potential mechanism for photosensitivity responses. PMID:19769579

  9. Results from the Nearby Stars (NStars) Program: Chromospheric Activity in a Sample of Nearby Solar Analogs

    NASA Astrophysics Data System (ADS)

    Corbally, Christopher J.; J., S.; Gray, R. O.

    2010-01-01

    Since the year 2000, our institutions have been engaged in a study of the nearby dwarf and giant stars earlier than spectral type M0 in the Hipparcos catalog and within 40 parsecs of the Sun (3600 stars). This study has used classification-resolution spectra to provide new, precise spectral types and basic physical parameters (effective temperature, surface gravity and metallicity). In addition, we are providing measures of the chromospheric activity for these stars. Results so far have been published in Gray et al. (2003, 2006). Here we outline the continuation of this study to which recent improvements have been made. These are both to the estimation of chromospheric activity, now closer to the Mount Wilson system, and to the derivation of stellar parameters through use of Kurucz's newer, Atlas12 atmospheric models. For a limited, improved sample, activity and evolutionary age are compared.

  10. Results From the Bipartisan Policy Center's CEO Council Physical Activity Challenge to American Business

    PubMed Central

    Berko, Jeff; Goetzel, Ron Z.; Roemer, Enid Chung; Kent, Karen; Marchibroda, Janet

    2016-01-01

    Objective: The aim of this study was to describe findings from a survey of employees at 10 businesses participating in the “Building Better Health: Physical Activity Challenge,” an effort led by the Bipartisan Policy Center's CEO Council on Health and Innovation. Methods: Employers provided employees with pedometers as part of an 8-week Physical Activity Challenge (Challenge). Employees were then asked to complete a survey about their awareness of, participation in, and satisfaction with the Challenge. Results: One hundred three thousand three hundred eighty-three employees participated in the Challenge, averaging 6886 steps per day per participant. Of the 3820 respondents to an employee survey sent to all workers, 62% reported enrolling in the program, and of those, the majority reported positive impacts on health (76%), fitness (73%), and lifestyle (70%). Conclusion: A brief, workplace-based physical activity challenge can achieve positive self-reported health impacts when supported by senior management of the company. PMID:27930485

  11. A strong strand displacement activity of thermostable DNA polymerase markedly improves the results of DNA amplification.

    PubMed

    Ignatov, Konstantin B; Barsova, Ekaterina V; Fradkov, Arkady F; Blagodatskikh, Konstantin A; Kramarova, Tatiana V; Kramarov, Vladimir M

    2014-08-01

    The sensitivity and robustness of various DNA detection and amplification techniques are to a large extent determined by the properties of the DNA polymerase used. We have compared the performance of conventional Taq and Bst DNA polymerases to a novel Taq DNA polymerase mutant (SD DNA polymerase), which has a strong strand displacement activity, in PCR (including amplification of GC-rich and complex secondary structure templates), long-range PCR (LR PCR), loop-mediated amplification (LAMP), and polymerase chain displacement reaction (PCDR). Our results demonstrate that the strand displacement activity of SD DNA polymerase, in combination with the robust polymerase activity, provides a notable improvement in the sensitivity and efficiency of all these methods.

  12. Detailed profiling of anti-desmoglein autoantibodies identifies anti-Dsg1 reactivity as a key driver of disease activity and clinical expression in pemphigus vulgaris.

    PubMed

    Naseer, S Y; Seiffert-Sinha, K; Sinha, A A

    2015-06-01

    With their near-universal presence in patients and ease of clinical measurement, anti-desmoglein (Dsg) antibodies serve as primary candidates for creating prognostic tools in Pemphigus vulgaris (PV). Although the desmoglein compensation hypothesis postulates a clear relationship between anti-Dsg autoantibodies and clinical phenotype in PV, recent studies have questioned the fidelity of this hypothesis as a predictor of lesion morphology. Moreover, few studies address the association of anti-Dsg antibodies to other clinical parameters such as disease phase and age at onset. Using the largest patient repository to date in PV, we present a detailed analysis of anti-desmoglein antibody profiles across a comprehensive range of dynamic (disease phase, therapy, lesion morphology) and temporal (disease duration, age at sampling, age at onset) clinical parameters. Our data highlight the non-traditional but key role of anti-Dsg1 levels in tracking disease activity. We show that declining anti-Dsg1 levels may predict progression from active phase to early remission and long-term maintenance of remission, regardless of lesion morphology. In contrast, many remittent patients have elevated levels of anti-Dsg3 without lesional activity. Furthermore, we describe a unique subset of remittent patients that develop chronic transient lesions (lasting <1 week) in the setting of elevated anti-Dsg3 levels but do not meet the consensus criteria for active phase. Re-classification of patients with transient lesions as "active" may shed new light on pathophysiological processes underlying cycles of blister formation and rapid spontaneous healing in PV. Additionally, we provide evidence for the potential attenuation of the immune response with prolonged disease duration. Our data fit into the broader effort of immunoprofiling to promote data-informed decision-making regarding diagnosis, prognosis and treatment of complex diseases.

  13. Differential expression of key regulators of Toll-like receptors in ulcerative colitis and Crohn's disease: a role for Tollip and peroxisome proliferator-activated receptor gamma?

    PubMed

    Fernandes, P; MacSharry, J; Darby, T; Fanning, A; Shanahan, F; Houston, A; Brint, E

    2016-03-01

    The innate immune system is currently seen as the probable initiator of events which culminate in the development of inflammatory bowel disease (IBD) with Toll-like receptors (TLRs) known to be involved in this disease process. Many regulators of TLRs have been described, and dysregulation of these may also be important in the pathogenesis of IBD. The aim of this study was to perform a co-ordinated analysis of the expression levels of both key intestinal TLRs and their inhibitory proteins in the same IBD cohorts, both ulcerative colitis (UC) and Crohn's disease (CD), in order to evaluate the potential roles of these proteins in the pathogenesis of IBD. Of the six TLRs (TLRs 1, 2, 4, 5, 6 and 9) examined, only TLR-4 was increased significantly in IBD, specifically in active UC. In contrast, differential alterations in expression of TLR inhibitory proteins were observed. A20 and suppressor of cytokine signalling 1 (SOCS1) were increased only in active UC while interleukin-1 receptor-associated kinase 1 (IRAK-m) and B cell lymphoma 3 protein (Bcl-3) were increased in both active UC and CD. In contrast, expression of both peroxisome proliferator-activated receptor gamma (PPARγ) and Toll interacting protein (Tollip) was decreased in both active and inactive UC and CD and at both mRNA and protein levels. In addition, expression of both PPARγ and A20 expression was increased by stimulation of a colonic epithelial cell line Caco-2 with both TLR ligands and commensal bacterial strains. These data suggest that IBD may be associated with distinctive changes in TLR-4 and TLR inhibitory proteins, implying that alterations in these may contribute to the pathogenesis of IBD.

  14. An immunogen containing four tandem 10E8 epitope repeats with exposed key residues induces antibodies that neutralize HIV-1 and activates an ADCC reporter gene.

    PubMed

    Sun, Zhiwu; Zhu, Yun; Wang, Qian; Ye, Ling; Dai, Yanyan; Su, Shan; Yu, Fei; Ying, Tianlei; Yang, Chinglai; Jiang, Shibo; Lu, Lu

    2016-06-22

    After three decades of intensive research efforts, an effective vaccine against HIV-1 remains to be developed. Several broadly neutralizing antibodies to HIV-1, such as 10E8, recognize the membrane proximal external region (MPER) of the HIV-1 gp41 protein. Thus, the MPER is considered to be a very important target for vaccine design. However, the MPER segment has very weak immunogenicity and tends to insert its epitope residues into the cell membrane, thereby avoiding antibody binding. To address this complication in vaccine development, we herein designed a peptide, designated 10E8-4P, containing four copies of the 10E8 epitope as an immunogen. As predicted by structural simulation, 10E8-4P exhibits a well-arranged tandem helical conformation, with the key residues in the 10E8 epitope oriented at different angles, thus suggesting that some of these key residues may be exposed outside of the lipid membrane. Compared with a peptide containing a single 10E8 epitope (10E8-1P), 10E8-4P not only exhibited better antigenicity but also elicited neutralizing antibody response against HIV-1 pseudoviruses, whereas 10E8-1P could not induce detectable neutralizing antibody response. Importantly, antibodies elicited by 10E8-4P also possessed a strong ability to activate an antibody-dependent cell-mediated cytotoxicity (ADCC) reporter gene, thus suggesting that they may have ADCC activity. Therefore, this strategy shows promise for further optimization and application in future HIV-1 vaccine design.

  15. Improving Nutrition and Physical Activity Policies in Afterschool Programs: Results from a Group-Randomized Controlled Trial

    PubMed Central

    Kenney, Erica L.; Giles, Catherine M.; deBlois, Madeleine E.; Gortmaker, Steven L.; Chinfatt, Sherene; Cradock, Angie L.

    2017-01-01

    OBJECTIVE Afterschool programs can be health-promoting environments for children. Written policies positively influence nutrition and physical activity (PA) environments, but effective strategies for building staff capacity to write such policies have not been evaluated. This study measures the comprehensiveness of written nutrition, PA, and screen time policies in afterschool programs and assesses impact of the Out of School Nutrition and Physical Activity (OSNAP) intervention on key policies. METHODS Twenty afterschool programs in Boston, MA participated in a group-randomized, controlled trial from September 2010 to June 2011. Intervention program staff attended learning collaboratives focused on practice and policy change. The Out-of-School Time (OST) Policy Assessment Index evaluated written policies. Inter-rater reliability and construct validity of the measure and impact of the intervention on written policies were assessed. RESULTS The measure demonstrated moderate to excellent inter-rater reliability (Spearman’s r=0.53 to 0.97) and construct validity. OSNAP was associated with significant increases in standards-based policy statements surrounding snacks (+2.6, p=0.003), beverages (+2.3, p=0.008), screen time (+0.8, p=0.046), family communication (+2.2, p=0.002), and a summary index of OSNAP goals (+3.3, p=0.02). CONCLUSIONS OSNAP demonstrated success in building staff capacity to write health-promoting policy statements. Future research should focus on determining policy change impact on practices. PMID:24941286

  16. Preliminary results of systematic sampling of gas manifestations in geodynamically active areas of Greece

    NASA Astrophysics Data System (ADS)

    Daskalopoulou, Kyriaki; D'Alessandro, Walter; Calabrese, Sergio; Kyriakopoulos, Konstantinos

    2016-04-01

    Greece is located on a convergent plate boundary comprising the subduction of the African Plate beneath the Eurasian, while the Arabian plate approaches the Eurasian in a northwestward motion. It is considered to be one of the most tectonically active regions of Earth with a complex geodynamic setting, deriving from a long and complicated geological history. Due to this specific geological background, conditions for the formation of many thermal springs are favoured. In the past years, almost all the already known sites of degassing (fumaroles, soil gases, mofettes, gas bubbling in cold and thermal waters) located in the Hellenic area were sampled at least one time. Collected samples were analysed for their chemical (He, Ne, Ar, O2, N2, H2, H2S, CO, CH4 and CO2) and isotopic composition (He, C and N). Some of these sites have been selected for systematic sampling. Four of them have records longer than 10 years with tens of samplings also considering some literature data. Two of the sites are located in active volcanic areas (Santorini and Nisyros) while the other two are close to actively spreading graben structures with intense seismic activity (Gulf of Korinth and Sperchios basin). Results allowed to define long term background values and also some interesting variation related to seismic or volcanic activity.

  17. Uncoupling Malt1 threshold function from paracaspase activity results in destructive autoimmune inflammation.

    PubMed

    Gewies, Andreas; Gorka, Oliver; Bergmann, Hanna; Pechloff, Konstanze; Petermann, Franziska; Jeltsch, Katharina M; Rudelius, Martina; Kriegsmann, Mark; Weichert, Wilko; Horsch, Marion; Beckers, Johannes; Wurst, Wolfgang; Heikenwalder, Mathias; Korn, Thomas; Heissmeyer, Vigo; Ruland, Jürgen

    2014-11-20

    The paracaspase Malt1 is a central regulator of antigen receptor signaling that is frequently mutated in human lymphoma. As a scaffold, it assembles protein complexes for NF-κB activation, and its proteolytic domain cleaves negative NF-κB regulators for signal enforcement. Still, the physiological functions of Malt1-protease are unknown. We demonstrate that targeted Malt1-paracaspase inactivation induces a lethal inflammatory syndrome with lymphocyte-dependent neurodegeneration in vivo. Paracaspase activity is essential for regulatory T cell (Treg) and innate-like B cell development, but it is largely dispensable for overcoming Malt1-dependent thresholds for lymphocyte activation. In addition to NF-κB inhibitors, Malt1 cleaves an entire set of mRNA stability regulators, including Roquin-1, Roquin-2, and Regnase-1, and paracaspase inactivation results in excessive interferon gamma (IFNγ) production by effector lymphocytes that drive pathology. Together, our results reveal distinct threshold and modulatory functions of Malt1 that differentially control lymphocyte differentiation and activation pathways and demonstrate that selective paracaspase blockage skews systemic immunity toward destructive autoinflammation.

  18. Defective CFTR-dependent CREB activation results in impaired spermatogenesis and azoospermia.

    PubMed

    Xu, Wen Ming; Chen, Jing; Chen, Hui; Diao, Rui Ying; Fok, Kin Lam; Dong, Jian Da; Sun, Ting Ting; Chen, Wen Ying; Yu, Mei Kuen; Zhang, Xiao Hu; Tsang, Lai Ling; Lau, Ann; Shi, Qi Xian; Shi, Qing Hua; Huang, Ping Bo; Chan, Hsiao Chang

    2011-01-01

    Cystic fibrosis (CF) is the most common life-limiting recessive genetic disease among Caucasians caused by mutations of the cystic fibrosis transmembrane conductance regulator (CFTR) with over 95% male patients infertile. However, whether CFTR mutations could affect spermatogenesis and result in azoospermia remains an open question. Here we report compromised spermatogenesis, with significantly reduced testicular weight and sperm count, and decreased cAMP-responsive element binding protein (CREB) expression in the testes of CFTR knockout mice. The involvement of CFTR in HCO(3) (-) transport and the expression of the HCO(3) (-) sensor, soluble adenylyl cyclase (sAC), are demonstrated for the first time in the primary culture of rat Sertoli cells. Inhibition of CFTR or depletion of HCO(3) (-) could reduce FSH-stimulated, sAC-dependent cAMP production and phosphorylation of CREB, the key transcription factor in spermatogenesis. Decreased CFTR and CREB expression are also observed in human testes with azoospermia. The present study reveals a previously undefined role of CFTR and sAC in regulating the cAMP-CREB signaling pathway in Sertoli cells, defect of which may result in impaired spermatogenesis and azoospermia. Altered CFTR-sAC-cAMP-CREB functional loop may also underline the pathogenesis of various CF-related diseases.

  19. F-8 digital fly-by-wire flight test results viewed from an active controls perspective

    NASA Technical Reports Server (NTRS)

    Zalai, K. J.; Deets, D. A.

    1975-01-01

    The results of the NASA F-8 digital fly-by-wire flight test program are presented, along with the implications for active controls applications. The closed loop performance of the digital control system agreed well with the sampled-data system design predictions. The digital fly-by-wire mechanization also met pilot flying qualities requirements. The advantages of mechanizing the control laws in software became apparent during the flight program and were realized without sacrificing overall system reliability. This required strict software management. The F-8 flight test results are shown to be encouraging in light of the requirements that must be met by control systems for flight-critical active controls applications.

  20. Testing and Oxygen Assessment Results for a Next Generation Extravehicular Activity Portable Life Support System Fan

    NASA Technical Reports Server (NTRS)

    Paul, Heather L.; Jennings, Mallory A.; Rivera, Fatonia L.; Martin, Devin

    2011-01-01

    NASA is designing a next generation Extravehicular Activity (EVA) Portable Life Support System (PLSS) for use in future surface exploration endeavors. To meet the new requirements for ventilation flow at nominal and buddy modes, a fan has been developed and tested. This paper summarizes the results of the performance and life cycle testing efforts conducted at the NASA Johnson Space Center. Additionally, oxygen compatibility assessment results from an evaluation conducted at White Sands Test Facility (WSTF) are provided, and lessons learned and future recommendations are outlined.

  1. Role of FKBP5 in emotion processing: results on amygdala activity, connectivity and volume.

    PubMed

    Holz, Nathalie E; Buchmann, Arlette F; Boecker, Regina; Blomeyer, Dorothea; Baumeister, Sarah; Wolf, Isabella; Rietschel, Marcella; Witt, Stephanie H; Plichta, Michael M; Meyer-Lindenberg, Andreas; Banaschewski, Tobias; Brandeis, Daniel; Laucht, Manfred

    2015-01-01

    Accumulating evidence suggests a role of FKBP5, a co-chaperone regulating the glucocorticoid receptor sensitivity, in the etiology of depression and anxiety disorders. Based on recent findings of altered amygdala activity following childhood adversity, the present study aimed at clarifying the impact of genetic variation in FKBP5 on threat-related neural activity and coupling as well as morphometric alterations in stress-sensitive brain systems. Functional magnetic resonance imaging during an emotional face-matching task was performed in 153 healthy young adults (66 males) from a high-risk community sample followed since birth. Voxel-based morphometry was applied to study structural alterations and DNA was genotyped for FKBP5 rs1360780. Childhood adversity was measured using retrospective self-report (Childhood Trauma Questionnaire) and by a standardized parent interview assessing childhood family adversity. Depression was assessed by the Beck Depression Inventory. There was a main effect of FKBP5 on the left amygdala, with T homozygotes showing the highest activity, largest volume and increased coupling with the left hippocampus and the orbitofrontal cortex (OFC). Moreover, amygdala-OFC coupling proved to be associated with depression in this genotype. In addition, our results support previous evidence of a gene-environment interaction on right amygdala activity with respect to retrospective assessment of childhood adversity, but clarify that this does not generalize to the prospective assessment. These findings indicated that activity in T homozygotes increased with the level of adversity, whereas the opposite pattern emerged in C homozygotes, with CT individuals being intermediate. The present results point to a functional involvement of FKBP5 in intermediate phenotypes associated with emotional processing, suggesting a possible mechanism for this gene in conferring susceptibility to stress-related disorders.

  2. Activation of hip prostheses in high energy radiotherapy and resultant dose to nearby tissue.

    PubMed

    Keehan, Stephanie; Smith, Ryan L; Millar, Jeremy; Esser, Max; Taylor, Michael L; Lonski, Peta; Kron, Tomas; Franich, Rick D

    2017-03-01

    High energy radiotherapy can produce contaminant neutrons through the photonuclear effect. Patients receiving external beam radiation therapy to the pelvis may have high-density hip prostheses. Metallic materials such as those in hip prostheses, often have high cross-sections for neutron interaction. In this study, Thackray (UK) prosthetic hips have been irradiated by 18 MV radiotherapy beams to evaluate the additional dose to patients from the activation products. Hips were irradiated in- and out-of field at various distances from the beam isocenter to assess activation caused in-field by photo-activation, and neutron activation which occurs both in and out-of-field. NaI(Tl) scintillator detectors were used to measure the subsequent gamma-ray emissions and their half-lives. High sensitivity Mg, Cu, P doped LiF thermoluminescence dosimeter chips (TLD-100H) were used to measure the subsequent dose at the surface of a prosthesis over the 12 h following an in-field irradiation of 10,000 MU to a hip prosthesis located at the beam isocenter in a water phantom. (53) Fe, (56) Mn, and (52) V were identified within the hip following irradiation by radiotherapy beams. The dose measured at the surface of a prosthesis following irradiation in a water phantom was 0.20 mGy over 12 h. The dose at the surface of prostheses irradiated to 200 MU was below the limit of detection (0.05 mGy) of the TLD100H. Prosthetic hips are activated by incident photons and neutrons in high energy radiotherapy, however, the dose resulting from activation is very small.

  3. Results of the pilot proof of the inquiry activities conducted in the science center

    NASA Astrophysics Data System (ADS)

    Kireš, Marián; BilišÅanská, Mária

    2017-01-01

    The science center SteelPARK Košice offers more than 60 interactive exhibits focused on presenting scientific principles and technical solutions connected to the production and manufacture of steel, research of its properties and its various industrial uses. We are trying to enhance the attractivity of the modern style of the exhibitions and its potential to engage students of ground and middle schools in acquiring new knowledge and capabilities, by means of the inquiry science center. Two laboratory measurements, for 5 three-person teams are provided once a month. During the introductory discussion on the activity, they are asked to answer a series of conceptual questions, which help determine their level of understanding at the beginning of the exercise. The measurements are based in guided inquiry, where the work progress is given a forehand, but the desired result is not. Every activity is focused on developing specific research capabilities. This is being monitored through a self-evaluation card, which every participants is required to fill out immediately after completing the activity. The work is tutored by a lecturer from the students of didactics. During two years and running 15 different activities, we have been able to gather information from more than 6000 students of ground and middle schools. Specific physics measurements, their respective conceptual questions, worksheets and final reports are being presented in this article. We evaluate the present level of conceptual understanding based on the acquired data and give recommendation to teachers on ways to improve the student's capabilities. The teacher, by way of observing the activity, the work of the lecturer and the students, is able to form an understanding of the inquiry activity for their own school practice, for which he/she can use all available methodical and work materials.

  4. How to report results of prothrombin and activated partial thromboplastin times.

    PubMed

    Tripodi, Armando; Lippi, Giuseppe; Plebani, Mario

    2016-02-01

    Prothrombin time (PT) and activated partial thromboplastin time (APTT) are the most widely used tests to investigate coagulation abnormalities. Varied result reporting have been introduced over the years for the two tests, thus making their interpretation rather confusing in different clinical settings. PT results have been reported as clotting time, percentage activity, PT-ratio (patient-to-normal clotting time) and as international normalized ratio (INR). The INR scale has been devised to harmonize results stemming from different thromboplastins from patients on treatment with vitamin K antagonists. Therefore, there are some theoretical and evidence-based considerations that make the INR formally invalid when the test is used to analyze patients in other clinical settings. Unfortunately, this limitation has been frequently overlooked, and the INR has been (and is currently) used as a universal system of results harmonization. The APTT has been historically reported as clotting time or as ratio (patient-to-normal clotting time). In this opinion paper we review the current state-of-the-art for result reporting and attempt to give practical guidance on how PT and APTT should be reported in different clinical conditions for which the tests are requested.

  5. Secure key storage and distribution

    DOEpatents

    Agrawal, Punit

    2015-06-02

    This disclosure describes a distributed, fault-tolerant security system that enables the secure storage and distribution of private keys. In one implementation, the security system includes a plurality of computing resources that independently store private keys provided by publishers and encrypted using a single security system public key. To protect against malicious activity, the security system private key necessary to decrypt the publication private keys is not stored at any of the computing resources. Rather portions, or shares of the security system private key are stored at each of the computing resources within the security system and multiple security systems must communicate and share partial decryptions in order to decrypt the stored private key.

  6. Evaluation of fine-particle catalysts: Activity testing results and phase identification using Mossbauer spectroscopy

    SciTech Connect

    Stohl, F.V.; Diegert, K.V.; Goodnow, D.; Rao, K.R.P.M.; Huggins, F.; Huffman, G.P.

    1994-10-01

    To evaluate and compare the activities/selectivities of fine- particle size catalysts being developed in the DOE/PETC Advanced Research (AR) Coal Liquefaction program by using standard coal liquefaction activity test procedures. Previously reported results have described the standard test procedure that was developed at Sandia to evaluate fine-particle size iron catalysts being developed in DOE/PETC`s AR Coal Liquefaction Program. This test uses DECS-17 Blind Canyon Coal, phenanthrene as the reaction solvent, and a factorial experimental design that enables evaluation of a catalyst over ranges of temperature (350 to 400{degrees}C), time (20 to 60 minutes), and catalyst loading (0 to 1 wt% on a dmmf coal basis). Testing has been performed on Pacific Northwest Laboratories` (PNL) 6-line ferrihydrite catalyst. Results showed that this catalyst is more active than the University of Pittsburgh`s sulfated iron oxide catalyst that was evaluated previously. PNL has also produced two additional batches of catalyst in an effort to optimize their preparation procedures for larger batches. Sandia has observed significant differences in activities among these three catalysts; these differences might be due to particle size effects, the type of drying procedure, or the amount of moisture present. Mossbauer characterization of the iron phases in the coal, catalyst precursors, and tetrahydrofuran (THF) insoluble material from liquefaction reactions has been performed on the University of Pittsburgh`s catalyst and the first PNL catalyst that was tested at Sandia. The Mossbauer results were obtained at the University of Kentucky and will be presented. Future work will include testing additional catalysts being developed in the AR Coal Liquefaction Program, developing procedures to characterize reaction products, and determining the kinetics of the reactions.

  7. An Activating Mutation in STAT3 Results in Neonatal Diabetes Through Reduced Insulin Synthesis.

    PubMed

    Velayos, Teresa; Martínez, Rosa; Alonso, Milagros; Garcia-Etxebarria, Koldo; Aguayo, Anibal; Camarero, Cristina; Urrutia, Inés; Martínez de LaPiscina, Idoia; Barrio, Raquel; Santin, Izortze; Castaño, Luis

    2017-04-01

    Neonatal diabetes mellitus (NDM) is a rare form of diabetes diagnosed within the first 6 months of life. Genetic studies have allowed the identification of several genes linked to the development of NDM; however, genetic causes for ∼20% of the cases remain to be clarified. Most cases of NDM involve isolated diabetes, but sometimes NDM appears in association with other pathological conditions, including autoimmune diseases. Recent reports have linked activating mutations in STAT3 with early-onset autoimmune disorders that include diabetes of autoimmune origin, but the functional impact of STAT3-activating mutations have not been characterized at the pancreatic β-cell level. By using whole-exome sequencing, we identified a novel missense mutation in the binding domain of the STAT3 protein in a patient with NDM. The functional analyses showed that the mutation results in an aberrant activation of STAT3, leading to deleterious downstream effects in pancreatic β-cells. The identified mutation leads to hyperinhibition of the transcription factor Isl-1 and, consequently, to a decrease in insulin expression. These findings represent the first functional indication of a direct link between an NDM-linked activating mutation in STAT3 and pancreatic β-cell dysfunction.

  8. Activation of thalamus in motor imagery results from gating by hypnosis.

    PubMed

    Müller, Katharina; Bacht, Katrin; Prochnow, Denise; Schramm, Stefanie; Seitz, Rüdiger J

    2013-02-01

    The ability to mentally imagine the performance of automatic movements has been well-established being employed in sports and physiotherapy as a tool for motor learning and rehabilitation. This is probably mediated by engagement of the same brain areas as during real motor performance. Here we investigated the effect of hypnotic trance on the cerebral activation pattern engaged in motor imagery in 16 healthy, right-handed subjects using fMRI. Motor imagery as compared with rest was related to activations in the left medial frontal areas (preSMA/SMA), prefrontal- and frontal areas, putamen and inferior parietal areas. When compared with performance of the same movements motor imagery resulted in activation of the left middle frontal cortex, precuneus, and posterior cingulate. Under hypnotic trance there was one extra-activation in the left thalamus which occurred specifically in the motor imagery condition. The regional beta indices were highly correlated among the areas of the cortical-subcortical motor network. Our data accord with the notion that hypnotic trance enhances the motor control circuit engaged in motor imagery by modulating the gating function of the thalamus.

  9. Healthful Eating and Physical Activity in the Home Environment: Results from Multi-Family Focus Groups

    PubMed Central

    Berge, Jerica M.; Arikian, Aimee; Doherty, William J.; Neumark-Sztainer, Dianne

    2012-01-01

    Objective To explore multiple family members’ perceptions of risk and protective factors for healthy eating and physical activity in the home. Design Ten multi-family focus groups were conducted with 26 families. Setting Community setting. Participants Primarily Black and White families. Family members (n = 103) were between the ages of 8–61 years. Analysis A grounded hermeneutic approach. Phenomenon of Interest Risk and protective factors for healthy eating and physical activity in the home environment. Results Ten major themes were identified by family members related to health behaviors in the home environment, including: (a) accessibility to healthy foods and activity, (b) time constraints, (c) stage of youth development, (d) individual investment in health behaviors, (e) family investment in health behaviors, (f) family meals and shared activities, (g) parent modeling, (h) making health behaviors fun, (i) making health behaviors part of the family lifestyle, and (j) community investment in family health behaviors. Conclusions and Implications This study identified the importance of the family system and the reciprocal influences within the home environment on health behaviors. In addition, individual and community-level suggestions were identified. Insights from the families provide leads for future research and ideas for the prevention of youth obesity. PMID:22192951

  10. Activities and geochronology of (137)Cs in lake sediments resulting from sediment resuspension.

    PubMed

    Matisoff, Gerald

    2017-02-01

    In lakes with a large surface area to watershed ratio (137)Cs delivery is primarily by direct atmospheric fallout to the lake surface, where its activity in the sediments has been used to estimate the exposure to organisms and sediment mass deposition rates. Comparison of (137)Cs in the historical atmospheric fallout record with (137)Cs activity profiles in sediment cores reveals that although the general features of a maxima in the fallout deposition can be matched to activity peaks in the core, the general shape of the (137)Cs profile is not an exact replica of the fallout history. Instead, the sediment reflects post-depositional processes such as resuspension, bioturbation, partitioning of (137)Cs between the sediment solids and the pore fluids, and molecular diffusion of (137)Cs through the pore fluids. Presented here is a model that couples these processes to a system time averaging (STA) model that accounts for the time history of (137)Cs fallout and the particle residence time in the water column or in the 'active' surface sediment subject to resuspension. Sediment profiles are examined by comparing reasonable ranges of each of the coefficients of each of these major processes and by applying the model to cores collected from two large, shallow lakes, Lake Erie (USA/Canada) and Lake Winnipeg (Canada). The results indicate that the STA model with molecular diffusion and sediment resuspension best describes the data from these large, shallow lakes.

  11. Mediated semiquantum key distribution

    NASA Astrophysics Data System (ADS)

    Krawec, Walter O.

    2015-03-01

    In this work, we design a quantum key distribution protocol, allowing two limited semiquantum or "classical" users to establish a shared secret key with the help of a fully quantum server. A semiquantum user can prepare and measure qubits only in the computational basis and so must rely on this quantum server to produce qubits in alternative bases and also to perform alternative measurements. However, we assume that the server is untrusted and we prove the unconditional security of our protocol even in the worst case: when this quantum server is an all-powerful adversary. We also compute a lower bound of the key rate of our protocol, in the asymptotic scenario, as a function of the observed error rate in the channel, allowing us to compute the maximally tolerated error of our protocol. Our results show that a semiquantum protocol may hold similar security to a fully quantum one.

  12. Probing the Active Site of MIO-dependent Aminomutases, Key Catalysts in the Biosynthesis of amino Acids Incorporated in Secondary Metabolites

    SciTech Connect

    Cooke, H.; Bruner, S

    2010-01-01

    The tyrosine aminomutase SgTAM produces (S)-{beta}-tyrosine from L-tyrosine in the biosynthesis of the enediyne antitumor antibiotic C-1027. This conversion is promoted by the methylideneimidazole-5-one (MIO) prosthetic group. MIO was first identified in the homologous family of ammonia lyases, which deaminate aromatic amino acids to form {alpha},{beta}-unsaturated carboxylates. Studies of substrate specificity have been described for lyases but there have been limited reports in altering the substrate specificity of aminomutases. Furthermore, it remains unclear as to what structural properties are responsible for catalyzing the presumed readdition of the amino group into the {alpha},{beta}-unsaturated intermediates to form {beta}-amino acids. Attempts to elucidate specificity and mechanistic determinants of SgTAM have also proved to be difficult as it is recalcitrant to perturbations to the active site via mutagenesis. An X-ray cocrystal structure of the SgTAM mutant of the catalytic base with L-tyrosine verified important substrate binding residues as well as the enzymatic base. Further mutagenesis revealed that removal of these crucial interactions renders the enzyme inactive. Proposed structural determinants for mutase activity probed via mutagenesis, time-point assays and X-ray crystallography revealed a complicated role for these residues in maintaining key quaternary structure properties that aid in catalysis.

  13. Overview on calibration and validation activities and first results for ESA's Soil Moisture and Ocean Salinity Mission

    NASA Astrophysics Data System (ADS)

    Mecklenburg, Susanne; Bouzinac, Catherine; Delwart, Steven; Lopez-Baeza, Ernesto

    The Soil Moisture and Ocean Salinity (SMOS) mission, launched on 2 November 2009, is the European Space Agency's (ESA) second Earth Explorer Opportunity mission. The scientific objectives of the SMOS mission directly respond to the current lack of global observations of soil moisture and ocean salinity, two key variables used in predictive hydrological, oceanographic and atmospheric models. SMOS observations will also provide information on the characteri-sation of ice and snow covered surfaces and the sea ice effect on ocean-atmosphere heat fluxes and dynamics, which affects large-scale processes of the Earth's climate system. A major undertaking in any environmental science related satellite mission are the calibration and validation activities. Calibration is an important prerequisite to the performance verifica-tion, which demonstrates that the instrument meets its requirements. It is also important for the validation of geophysical parameters, such as soil moisture and sea surface salinity. The validation of the data will be handled through a combination of ESA led activities and national efforts. The SMOS Validation and Retrieval Team (SVRT) comprises the scientific contributions that will be made by the projects selected in response to the SMOS calibration and validation Announcement of Opportunity in 2005 as well as the two level 2 Expert Support Laboratories being involved in the development of the soil moisture and sea surface salinity data products. For the validation of the soil moisture data products ESA's activities will focus on two main sites, the Valencia Anchor Station, located in the East of Spain, and the Upper Danube Catchment, located in the South of Germany. In preparation to the SMOS commissioning phase, airborne rehearsal campaigns were conducted in spring 2008 over both aforementioned key sites and will be repeated, in collaboration with the French Space Agency CNES, in spring 2010. These will be coupled with a SMOS matchup generation

  14. Whole Blood Activation Results in Altered T Cell and Monocyte Cytokine Production Profiles by Flow Cytometry

    NASA Technical Reports Server (NTRS)

    Crucian, Brian E.; Sams, Clarence F.

    2001-01-01

    An excellent monitor of the immune balance of peripheral circulating cells is to determine their cytokine production patterns in response to stimuli. Using flow cytometry, a positive identification of cytokine producing cells in a mixed culture may be achieved. Recently, the ability to assess cytokine production following a whole-blood activation culture has been described. In this study, whole blood activation was compared to traditional PBMC activation and the individual cytokine secretion patterns for both T cells, T cell subsets and monocytes was determined by flow cytometry. RESULTS: For T cell cytokine assessment (IFNg/IL-10 and IL-21/L-4) following PMA +ionomycin activation: (1) a Significantly greater percentages of T cells producing IFNgamma and IL-2 were observed following whole-blood culture and (2) altered T cell cytokine production kinetics were observed by varying whole blood culture times. Four-color analysiS was used to allow assessment of cytokine production by specific T cell subsets. It was found that IFNgamma production was significantly elevated in the CD3+/CD8+ T cell population as compared to the CD3+/CD8- population following five hours of whole blood activation. Conversely, IL-2 and IL-10 production were Significantly elevated in the CD3+/CD8- T cell population as compared to the CD3+/CD8+ population. Monocyte cytokine production was assessed in both culture systems following LPS activation for 24 hours. A three-color flow cytometric was used to assess two cytokines (IL-1a/IL-12 and TNFa/IL-10) in conjunction with CD14. Nearly all monocytes were stimulated to produce IL-1a, IL-12 and TNFa. equally well in both culture systems, however monocyte production of IL-10 was significantly elevated in whole blood culture as compared to PBMC culture. IL-12 producing monocytes appeared to be a distinct subpopulation of the IL-1a producing set, whereas IL-10 and TNFa producing monocytes were largely mutually exclusive. IL-10 and TNFa producing

  15. Additive reductions in zebrafish PRPS1 activity result in a spectrum of deficiencies modeling several human PRPS1-associated diseases

    PubMed Central

    Pei, Wuhong; Xu, Lisha; Varshney, Gaurav K.; Carrington, Blake; Bishop, Kevin; Jones, MaryPat; Huang, Sunny C.; Idol, Jennifer; Pretorius, Pamela R.; Beirl, Alisha; Schimmenti, Lisa A.; Kindt, Katie S.; Sood, Raman; Burgess, Shawn M.

    2016-01-01

    Phosphoribosyl pyrophosphate synthetase-1 (PRPS1) is a key enzyme in nucleotide biosynthesis, and mutations in PRPS1 are found in several human diseases including nonsyndromic sensorineural deafness, Charcot-Marie-Tooth disease-5, and Arts Syndrome. We utilized zebrafish as a model to confirm that mutations in PRPS1 result in phenotypic deficiencies in zebrafish similar to those in the associated human diseases. We found two paralogs in zebrafish, prps1a and prps1b and characterized each paralogous mutant individually as well as the double mutant fish. Zebrafish prps1a mutants and prps1a;prps1b double mutants showed similar morphological phenotypes with increasingly severe phenotypes as the number of mutant alleles increased. Phenotypes included smaller eyes and reduced hair cell numbers, consistent with the optic atrophy and hearing impairment observed in human patients. The double mutant also showed abnormal development of primary motor neurons, hair cell innervation, and reduced leukocytes, consistent with the neuropathy and recurrent infection of the human patients possessing the most severe reductions of PRPS1 activity. Further analyses indicated the phenotypes were associated with a prolonged cell cycle likely resulting from reduced nucleotide synthesis and energy production in the mutant embryos. We further demonstrated the phenotypes were caused by delays in the tissues most highly expressing the prps1 genes. PMID:27425195

  16. Enhancing activated-peroxide formulations for porous materials: Test methods and results

    SciTech Connect

    Krauter, Paula; Tucker, Mark D.; Tezak, Matthew S.; Boucher, Raymond

    2012-12-01

    During an urban wide-area incident involving the release of a biological warfare agent, the recovery/restoration effort will require extensive resources and will tax the current capabilities of the government and private contractors. In fact, resources may be so limited that decontamination by facility owners/occupants may become necessary and a simple decontamination process and material should be available for this use. One potential process for use by facility owners/occupants would be a liquid sporicidal decontaminant, such as pHamended bleach or activated-peroxide, and simple application devices. While pH-amended bleach is currently the recommended low-tech decontamination solution, a less corrosive and toxic decontaminant is desirable. The objective of this project is to provide an operational assessment of an alternative to chlorine bleach for low-tech decontamination applications activated hydrogen peroxide. This report provides the methods and results for activatedperoxide evaluation experiments. The results suggest that the efficacy of an activated-peroxide decontaminant is similar to pH-amended bleach on many common materials.

  17. Modulation of the hormone setting by Rhodococcus fascians results in ectopic KNOX activation in Arabidopsis.

    PubMed

    Depuydt, Stephen; Dolezal, Karel; Van Lijsebettens, Mieke; Moritz, Thomas; Holsters, Marcelle; Vereecke, Danny

    2008-03-01

    The biotrophic actinomycete Rhodococcus fascians has a profound impact on plant development and a common aspect of the symptomatology is the deformation of infected leaves. In Arabidopsis (Arabidopsis thaliana), the serrated leaf margins formed upon infection resemble the leaf phenotype of transgenic plants with ectopic expression of KNOTTED-like homeobox (KNOX) genes. Through transcript profiling, we demonstrate that class-I KNOX genes are transcribed in symptomatic leaves. Functional analysis revealed that BREVIPEDICELLUS/KNOTTED-LIKE1 and mainly SHOOT MERISTEMLESS were essential for the observed leaf dissection. However, these results also positioned the KNOX genes downstream in the signaling cascade triggered by R. fascians infection. The much faster activation of ARABIDOPSIS RESPONSE REGULATOR5 and the establishment of homeostatic and feedback mechanisms to control cytokinin (CK) levels support the overrepresentation of this hormone in infected plants due to the secretion by the pathogen, thereby placing the CK response high up in the cascade. Hormone measurements show a net decrease of tested CKs, indicating either that secretion by the bacterium and degradation by the plant are in balance, or, as suggested by the strong reaction of 35S:CKX plants, that other CKs are at play. At early time points of the interaction, activation of gibberellin 2-oxidase presumably installs a local hormonal setting favorable for meristematic activity that provokes leaf serrations. The results are discussed in the context of symptom development, evasion of plant defense, and the establishment of a specific niche by R. fascians.

  18. Incorporation of Cobalt‐Cyclen Complexes into Templated Nanogels Results in Enhanced Activity

    PubMed Central

    Jorge, Ana Rita; Chernobryva, Mariya; Rigby, Stephen E. J.

    2015-01-01

    Abstract Recent advances in nanomaterials have identified nanogels as an excellent matrix for novel biomimetic catalysts using the molecular imprinting approach. Polymerisable Co‐cyclen complexes with phosphonate and carbonate templates have been prepared, fully characterised and used to obtain nanogels that show high activity and turnover with low catalytic load, compared to the free complex, in the hydrolysis of 4‐nitrophenyl phosphate, a nerve agent simulant. This work demonstrates that the chemical structure of the template has an impact on the coordination geometry and oxidation state of the metal centre in the polymerisable complex resulting in very significant changes in the catalytic properties of the polymeric matrix. Both pseudo‐octahedral cobalt(III) and trigonal‐bipyramidal cobalt(II) structures have been used for the synthesis of imprinted nanogels, and the catalytic data demonstrate that: i) the imprinted nanogels can be used in 15 % load and show turnover; ii) the structural differences in the polymeric matrices resulting from the imprinting approach with different templates are responsible for the molecular recognition capabilities and the catalytic activity. Nanogel P1, imprinted with the carbonate template, shows >50 % higher catalytic activity than P2 imprinted with the phosphonate. PMID:26661923

  19. Changes in the cardiac muscle electric activity as a result of Coronary Artery Bypass Graft operation

    NASA Astrophysics Data System (ADS)

    Grajek, Magdalena; Krzyminiewski, Ryszard; Kalawski, Ryszard; Kulczak, Mariusz

    2008-01-01

    Many bioelectric signals have a complex internal structure that can be a rich source of information on the tissue or cell processes. The structure of such signals can be analysed in detail by applying digital methods of signal processing. Therefore, of substantial use in diagnosis of the coronary arterial disease is the method of digital enhancement of increasing signal resolution ECG (NURSE-ECG), permitting detection of temporary changes in the electric potentials in the cardiac muscle in the process of depolarisation. Thanks to the application of NURSE-ECG it has become possible to detect relatively small changes in the electric activity of particular fragments of the cardiac muscle undetectable by the standard ECG method, caused by ischemia, the effect of a drug or infarct. The aim of this study was to identify and analyse changes in the electric activity of the cardiac muscle as a result of the Coronary Artery Bypass Graft (CABG) operation. In this study the method of NURSE-ECG has been applied in order to identify and analyse changes in the electric activity of the cardiac muscle as a result of the CABG operation. In the study performed in cooperation of the Institute of Physics Adam Mickiewicz University and the Strus Hospital, Cardiac Surgery Ward, 37 patients with advanced coronary arterial disease were asked to participate. The patients were examined prior to the operation, on the day after the operation and two months after the operation and a year after the operation. The ECG recordings were subjected to a numerical procedure of resolution enhancement by a NURSE-ECG program to reveal the tentative changes in the electric potential of the cardiac muscle on its depolarisation. Results of the study have shown that the NURSE ECG method can be applied to monitor changes in the electric activity of the cardiac muscle occurring as a result of CABG operation. One the second day after the operation in the majority of patients (70%) a rapid decrease of the total

  20. Automated secured cost effective key refreshing technique to enhance WiMAX privacy key management

    NASA Astrophysics Data System (ADS)

    Sridevi, B.; Sivaranjani, S.; Rajaram, S.

    2013-01-01

    In all walks of life the way of communication is transformed by the rapid growth of wireless communication and its pervasive use. A wireless network which is fixed and richer in bandwidth is specified as IEEE 802.16, promoted and launched by an industrial forum is termed as Worldwide Interoperability for Microwave Access (WiMAX). This technology enables seamless delivery of wireless broadband service for fixed and/or mobile users. The obscurity is the long delay which occurs during the handoff management in every network. Mobile WiMAX employs an authenticated key management protocol as a part of handoff management in which the Base Station (BS) controls the distribution of keying material to the Mobile Station (MS). The protocol employed is Privacy Key Management Version 2- Extensible Authentication Protocol (PKMV2-EAP) which is responsible for the normal and periodical authorization of MSs, reauthorization as well as key refreshing. Authorization key (AK) and Traffic Encryption key (TEK) plays a vital role in key exchange. When the lifetime of key expires, MS has to request for a new key to BS which in turn leads to repetition of authorization, authentication as well as key exchange. To avoid service interruption during reauthorization , two active keys are transmitted at the same time by BS to MS. The consequences of existing work are hefty amount of bandwidth utilization, time consumption and large storage. It is also endured by Man in the Middle attack and Impersonation due to lack of security in key exchange. This paper designs an automatic mutual refreshing of keys to minimize bandwidth utilization, key storage and time consumption by proposing Previous key and Iteration based Key Refreshing Function (PKIBKRF). By integrating PKIBKRF in key generation, the simulation results indicate that 21.8% of the bandwidth and storage of keys are reduced and PKMV2 mutual authentication time is reduced by 66.67%. The proposed work is simulated with Qualnet model and

  1. Mitogen-Activated Protein Kinase Phosphatase-1 Is a Key Regulator of Hypoxia-Induced Vascular Endothelial Growth Factor Expression and Vessel Density in Lung

    PubMed Central

    Shields, Kristin M.; Panzhinskiy, Evgeniy; Burns, Nana; Zawada, W. Michael; Das, Mita

    2011-01-01

    Although mitogen-activated protein kinase phosphatase-1 (MKP-1) is a key deactivator of MAP kinases, known effectors of lung vessel formation, whether it plays a role in the expression of proangiogenic vascular endothelial growth factor (VEGF) in hypoxic lung is unknown. We therefore hypothesized that MKP-1 is a crucial modulator of hypoxia-stimulated vessel development by regulating lung VEGF levels. Wild-type MKP-1+/+, heterozygous MKP-1+/−, and deficient MKP-1−/− mice were exposed to sea level (SL), Denver altitude (DA) (1609 m [5280 feet]), and severe high altitude (HYP) (∼5182 m [∼17,000 feet]) for 6 weeks. Hypoxia enhanced phosphorylation of p38 MAP kinase, a substrate of MKP-1, as well as α smooth muscle actin (αSMA) expression in vessels, respiratory epithelium, and interstitium of phosphatase-deficient lung. αSMA-positive vessel (<50 μm outside diameter) densities were markedly reduced, whereas vessel wall thickness was increased in hypoxic MKP-1−/− lung. Mouse embryonic fibroblasts (MEFs) of all three genotypes were isolated to pinpoint the mechanism involved in hypoxia-induced vascular abnormalities of MKP-1−/− lung. Sustained phosphorylation of p38 MAP kinase was observed in MKP-1-null MEFs in response to hypoxia exposure. Although hypoxia up-regulated VEGF levels in MKP-1+/+ MEFs eightfold, only a 70% increase in VEGF expression was observed in MKP-1-deficient cells. Therefore, our data strongly suggest that MKP-1 might be the key regulator of vascular densities through the regulation of VEGF levels in hypoxic lung. PMID:21224048

  2. Structural and Biochemical Characterization of a Copper-Binding Mutant of the Organomercurial Lyase MerB: Insight into the Key Role of the Active Site Aspartic Acid in Hg-Carbon Bond Cleavage and Metal Binding Specificity.

    PubMed

    Wahba, Haytham M; Lecoq, Lauriane; Stevenson, Michael; Mansour, Ahmed; Cappadocia, Laurent; Lafrance-Vanasse, Julien; Wilkinson, Kevin J; Sygusch, Jurgen; Wilcox, Dean E; Omichinski, James G

    2016-02-23

    In bacterial resistance to mercury, the organomercurial lyase (MerB) plays a key role in the detoxification pathway through its ability to cleave Hg-carbon bonds. Two cysteines (C96 and C159; Escherichia coli MerB numbering) and an aspartic acid (D99) have been identified as the key catalytic residues, and these three residues are conserved in all but four known MerB variants, where the aspartic acid is replaced with a serine. To understand the role of the active site serine, we characterized the structure and metal binding properties of an E. coli MerB mutant with a serine substituted for D99 (MerB D99S) as well as one of the native MerB variants containing a serine residue in the active site (Bacillus megaterium MerB2). Surprisingly, the MerB D99S protein copurified with a bound metal that was determined to be Cu(II) from UV-vis absorption, inductively coupled plasma mass spectrometry, nuclear magnetic resonance, and electron paramagnetic resonance studies. X-ray structural studies revealed that the Cu(II) is bound to the active site cysteine residues of MerB D99S, but that it is displaced following the addition of either an organomercurial substrate or an ionic mercury product. In contrast, the B. megaterium MerB2 protein does not copurify with copper, but the structure of the B. megaterium MerB2-Hg complex is highly similar to the structure of the MerB D99S-Hg complexes. These results demonstrate that the active site aspartic acid is crucial for both the enzymatic activity and metal binding specificity of MerB proteins and suggest a possible functional relationship between MerB and its only known structural homologue, the copper-binding protein NosL.

  3. Maintaining physical activity during head and neck cancer treatment: Results of a pilot controlled trial

    PubMed Central

    Zhao, Shuang G.; Alexander, Neil B.; Djuric, Zora; Zhou, Jessica; Tao, Yebin; Schipper, Matthew; Feng, Felix Y.; Eisbruch, Avraham; Worden, Francis P.; Strath, Scott J.; Jolly, Shruti

    2017-01-01

    Background Concurrent chemoradiotherapy (concurrent CRT) to treat head and neck cancer is associated with significant reductions of weight, mobility, and quality of life (QOL). An intervention focusing on functional exercise may attenuate these losses. Methods We allocated patients to a 14-week functional resistance and walking program designed to maintain physical activity during cancer treatment (MPACT group; n = 11), or to usual care (control group; n = 9). Outcomes were assessed at baseline, and 7 and 14 weeks. Results Compared to controls, the MPACT participants had attenuated decline or improvement in several strength, mobility, physical activity, diet, and QOL endpoints. These trends were statistically significant (p < .05) in knee strength, mental health, head and neck QOL, and barriers to exercise. Conclusion In this pilot study of patients with head and neck cancer undergoing concurrent CRT, MPACT training was feasible and maintained or improved function and QOL, thereby providing the basis for larger future interventions with longer follow-up. PMID:26445898

  4. TRPA1 activation by lidocaine in nerve terminals results in glutamate release increase

    SciTech Connect

    Piao, L.-H.; Fujita, Tsugumi; Jiang, C.-Y.; Liu Tao; Yue, H.-Y.; Nakatsuka, Terumasa; Kumamoto, Eiichi

    2009-02-20

    We examined the effects of local anesthetics lidocaine and procaine on glutamatergic spontaneous excitatory transmission in substantia gelatinosa (SG) neurons in adult rat spinal cord slices with whole-cell patch-clamp techniques. Bath-applied lidocaine (1-5 mM) dose-dependently and reversibly increased the frequency but not the amplitude of spontaneous excitatory postsynaptic current (sEPSC) in SG neurons. Lidocaine activity was unaffected by the Na{sup +}-channel blocker, tetrodotoxin, and the TRPV1 antagonist, capsazepine, but was inhibited by the TRP antagonist, ruthenium red. In the same neuron, the TRPA1 agonist, allyl isothiocyanate, and lidocaine both increased sEPSC frequency. In contrast, procaine did not produce presynaptic enhancement. These results indicate that lidocaine activates TRPA1 in nerve terminals presynaptic to SG neurons to increase the spontaneous release of L-glutamate.

  5. TRPA1 activation by lidocaine in nerve terminals results in glutamate release increase.

    PubMed

    Piao, Lian-Hua; Fujita, Tsugumi; Jiang, Chang-Yu; Liu, Tao; Yue, Hai-Yuan; Nakatsuka, Terumasa; Kumamoto, Eiichi

    2009-02-20

    We examined the effects of local anesthetics lidocaine and procaine on glutamatergic spontaneous excitatory transmission in substantia gelatinosa (SG) neurons in adult rat spinal cord slices with whole-cell patch-clamp techniques. Bath-applied lidocaine (1-5 mM) dose-dependently and reversibly increased the frequency but not the amplitude of spontaneous excitatory postsynaptic current (sEPSC) in SG neurons. Lidocaine activity was unaffected by the Na(+)-channel blocker, tetrodotoxin, and the TRPV1 antagonist, capsazepine, but was inhibited by the TRP antagonist, ruthenium red. In the same neuron, the TRPA1 agonist, allyl isothiocyanate, and lidocaine both increased sEPSC frequency. In contrast, procaine did not produce presynaptic enhancement. These results indicate that lidocaine activates TRPA1 in nerve terminals presynaptic to SG neurons to increase the spontaneous release of L-glutamate.

  6. Interleukin-1 activates a novel protein kinase cascade that results in the phosphorylation of Hsp27.

    PubMed

    Freshney, N W; Rawlinson, L; Guesdon, F; Jones, E; Cowley, S; Hsuan, J; Saklatvala, J

    1994-09-23

    An IL-1-stimulated protein kinase cascade resulting in phosphorylation of the small heat shock protein hsp27 has been identified in KB cells. It is distinct from the p42 MAP kinase cascade. An upstream activator kinase phosphorylated a 40 kDa kinase (p40) upon threonine and tyrosine residues, which in turn phosphorylated a 50 kDa kinase (p50) upon threonine (and some serine) residues. p50 phosphorylated hsp27 upon serine. p40 and p50 were purified to near homogeneity. All three components were inactivated by protein phosphatase 2A, and p40 was inactivated by protein tyrosine phosphatase 1B. The substrate specificity of p40 differed from that of p42 and p54 MAP kinases. The upstream activator was not a MAP kinase kinase. p50 resembled MAPKAPK-2 and may be identical.

  7. Social support and physical activity change in Latinas: Results from the Seamos Saludables trial

    PubMed Central

    Marquez, Becky; Dunsiger, Shira I.; Pekmezi, Dori; Larsen, Britta A.; Marcus, Bess H.

    2016-01-01

    Objective Family responsibilities and poor social support are barriers to physical activity among Latinas. This study evaluated the effects of a home- and print-based intervention on social support, moderating effects of familial ties on support and moderate-to-vigorous physical activity (MVPA), and mediating effects of support on MVPA. Methods Participants were randomized to receive through the mail either individually tailored physical activity intervention or general wellness print materials. Familial ties and social support were assessed by marital and child status and the social support for physical activity measure, respectively. MVPA was measured using the 7-day Physical Activity Recall Interview and accelerometer. Assessments were conducted at baseline, 6 months post-treatment, and 12 months follow-up. Results Participants (n=266; 40.6 ± 9.9 years old) were mostly immigrant and Spanish-speaking Latinas. The intervention group achieved greater increases in family and friend support compared to the wellness control group from baseline to post-treatment and follow-up (p<0.05). Intervention changes in support did not depend on marital or child status. The intervention also increased minutes per week of MVPA more than the wellness control (p<0.05) and the effect did not depend on marital or child status. There were significant indirect effects of treatment, indicating the intervention achieved greater increases in MVPA by increasing family (ab=5.21, SE=2.94, 95% CI=0.91–14.11) and friend (ab=6.83, SE=5.15, 95% CI=0.16–20.56) support. Conclusions The intervention improved and sustained support from family and friends and MVPA irrespective of familial ties. Social support mediated increases in MVPA. PMID:26863464

  8. Delta-1 Activation of Notch-1 Signaling Results in HES-1 Transactivation

    PubMed Central

    Jarriault, Sophie; Le Bail, Odile; Hirsinger, Estelle; Pourquié, Olivier; Logeat, Frédérique; Strong, Clare F.; Brou, Christel; Seidah, Nabil G.; Israël, Alain

    1998-01-01

    The Notch receptor is involved in many cell fate determination events in vertebrates and invertebrates. It has been shown in Drosophila melanogaster that Delta-dependent Notch signaling activates the transcription factor Suppressor of Hairless, leading to an increased expression of the Enhancer of Split genes. Genetic evidence has also implicated the kuzbanian gene, which encodes a disintegrin metalloprotease, in the Notch signaling pathway. By using a two-cell coculture assay, we show here that vertebrate Dl-1 activates the Notch-1 cascade. Consistent with previous data obtained with active forms of Notch-1 a HES-1-derived promoter construct is transactivated in cells expressing Notch-1 in response to Dl-1 stimulation. Impairing the proteolytic maturation of the full-length receptor leads to a decrease in HES-1 transactivation, further supporting the hypothesis that only mature processed Notch is expressed at the cell surface and activated by its ligand. Furthermore, we observed that Dl-1-induced HES-1 transactivation was dependent both on Kuzbanian and RBP-J activities, consistent with the involvement of these two proteins in Notch signaling in Drosophila. We also observed that exposure of Notch-1-expressing cells to Dl-1 results in an increased level of endogenous HES-1 mRNA. Finally, coculture of Dl-1-expressing cells with myogenic C2 cells suppresses differentiation of C2 cells into myotubes, as previously demonstrated for Jagged-1 and Jagged-2, and also leads to an increased level of endogenous HES-1 mRNA. Thus, Dl-1 behaves as a functional ligand for Notch-1 and has the same ability to suppress cell differentiation as the Jagged proteins do. PMID:9819428

  9. Gender, body mass index and rheumatoid arthritis disease activity: results from the QUEST-RA study

    PubMed Central

    Jawaheer, Damini; Olsen, Jørn; Lahiff, Maureen; Forsberg, Sinikka; Lähteenmäki, Jukka; Silveira, Ines Guimaraes da; Rocha, Francisco Airton; Laurindo, Ieda Maria Magalhães; Mota, Licia Maria Henrique da; Drosos, Alexandros A.; Murphy, Eithne; Sheehy, Claire; Quirke, Edel; Cutolo, Maurizio; Rexhepi, Sylejman; Dadoniene, Jolanta; Verstappen, Suzan M.M.; Sokka, Tuulikki

    2010-01-01

    Objective To investigate whether body mass index (BMI), as a proxy for body fat, influences rheumatoid arthritis (RA) disease activity in a gender-specific manner. Methods Consecutive patients with RA were enrolled from 25 countries into the QUEST-RA program between 2005 and 2008. Clinical and demographic data were collected by treating rheumatologists and by patient self-report. Distributions of Disease Activity Scores (DAS28), BMI, age, and disease duration were assessed for each country and for the entire dataset; mean values between genders were compared using Student’s t-tests. An association between BMI and DAS28 was investigated using linear regression, adjusting for age, disease duration and country. Results A total of 5,161 RA patients (4,082 women and 1,079 men) were included in the analyses. Overall, women were younger, had longer disease duration, and higher DAS28 scores than men, but BMI was similar between genders. The mean DAS28 scores increased with increasing BMI from normal to overweight and obese, among women, whereas the opposite trend was observed among men. Regression results showed BMI (continuous or categorical) to be associated with DAS28. Compared to the normal BMI range, being obese was associated with a larger difference in mean DAS28 (0.23, 95% CI: 0.11, 0.34) than being overweight (0.12, 95% CI: 0.03, 0.21); being underweight was not associated with disease activity. These associations were more pronounced among women, and were not explained by any single component of the DAS28. Conclusion BMI appears to be associated with RA disease activity in women, but not in men. PMID:20810033

  10. Long term results of mechanical prostheses for treatment of active infective endocarditis

    PubMed Central

    Guerra, J; Tornos, M; Permanyer-Miralda, G; Almirante, B; Murtra, M; Soler-Soler, J

    2001-01-01

    OBJECTIVE—To analyse the long term results of mechanical prostheses for treating active infective endocarditis.
DESIGN—Prospective cohort study of a consecutive series of patients diagnosed with infective endocarditis and operated on in the active phase of the infection for insertion of a mechanical prosthesis.
SETTING—Tertiary referral centre in a metropolitan area.
RESULTS—Between 1975 and 1997, 637 cases of infective endocarditis were diagnosed in the centre. Of these, 436 were left sided (with overall mortality of 20.3%). Surgical treatment in the active phase of the infection was needed in 141 patients (72% native, 28% prosthetic infective endocarditis). Mechanical prostheses were used in 131 patients. Operative mortality was 30.5% (40 patients). Ninety one survivors were followed up prospectively for (mean (SD)) 5.4 (4.5) years. Thirteen patients developed prosthetic valve dysfunction. Nine patients suffered reinfection: four of these (4%) were early and five were late. The median time from surgery for late reinfection was 1.4 years. During follow up, 12 patients died. Excluding operative mortality, actuarial survival was 86.6% at five years and 83.7% at 10 years; actuarial survival free from death, reoperation, and reinfection was 73.1% at five years and 59.8% at 10 years.
CONCLUSIONS—In patients surviving acute infective endocarditis and receiving mechanical prostheses, the rate of early reinfection compares well with reported results of homografts. In addition, prosthesis dysfunction rate is low and long term survival is good. These data should prove useful for comparison with long term studies, when available, using other types of valve surgery in active infective endocarditis.


Keywords: infective endocarditis; surgery; mechanical prosthesis PMID:11410564

  11. Environmental systems and management activities on the Kennedy Space Center, Merritt Island, Florida: results of a modeling workshop

    USGS Publications Warehouse

    Hamilton, David B.; Andrews, Austin K.; Auble, Gregor T.; Ellison, Richard A.; Farmer, Adrian H.; Roelle, James E.

    1985-01-01

    In the early 1960's, the National Aeronautics and Space Administration (NASA) began purchasing 140,000 acres on Merritt Island, Florida, in order to develop a center for space exploration. Most of this land was acquired to provide a safety and security buffer around NASA facilities. NASA, as the managing agency for the Kennedy Space Center (KSC), is responsible for preventing or controlling environmental pollution from the Federal facilities and activities at the Space Center and is committed to use all practicable means to protect and enhance the quality of the surrounding environment. The Merritt Island National Wildlife Refuge was established in 1963 when management authority for undeveloped lands at KSC was transferred to the U.S. Fish and Wildlife Service. In addition to manage for 11 Federally-listed threatened and endangered species and other resident and migratory fish and wildlife populations, the Refuge has comanagement responsibility for 19,000 acres of mosquito control impoundments and 2,500 acres of citrus groves. The Canaveral National Seashore was developed in 1975 when management of a portion of the coastal lands was transferred from NASA to the National Park Service. This multiagency jurisdiction on Merritt Island has resulted in a complex management environment. The modeling workshop described in this report was conducted May 21-25, 1984, at the Kennedy Space Center to: (1) enhance communication among the agencies with management responsibilities on Merritt Island; (2) integrate available information concerning the development, management, and ecology of Merritt Island; and (3) identify key research and monitoring needs associated with the management and use of the island's resources. The workshop was structured around the formulation of a model that would simulate primary management and use activities on Merritt Island and their effects on upland, impoundment, and estuarine vegetation and associated wildlife. The simulation model is composed of

  12. Activation of TLR3/interferon signaling pathway by bluetongue virus results in HIV inhibition in macrophages.

    PubMed

    Dai, Ming; Wang, Xu; Li, Jie-Liang; Zhou, Yu; Sang, Ming; Liu, Jin-Biao; Wu, Jian-Guo; Ho, Wen-Zhe

    2015-12-01

    Bluetongue virus (BTV), a nonenveloped double-stranded RNA virus, is a potent inducer of type Ι interferons in multiple cell systems. In this study, we report that BTV16 treatment of primary human macrophages induced both type I and III IFN expression, resulting in the production of multiple antiviral factors, including myxovirus resistance protein A, 2',5'-oligoadenylate synthetase, and the IFN-stimulated gene 56. Additionally, BTV-treated macrophages expressed increased HIV restriction factors (apolipoprotein B mRNA-editing enzyme catalytic polypeptide 3 G/F/H) and CC chemokines (macrophage inflammatory protein 1-α, macrophage inflammatory protein 1-β, regulated on activation of normal T cell expressed and secreted), the ligands for HIV entry coreceptor CC chemokine receptor type 5. BTV16 also induced the expression of tetherin, which restricts HIV release from infected cells. Furthermore, TLR3 signaling of macrophages by BTV16 resulted in the induction of several anti-HIV microRNAs (miRNA-28, -29a, -125b, -150, -223, and -382). More importantly, the induction of antiviral responses by BTV resulted in significant suppression of HIV in macrophages. These findings demonstrate the potential of BTV-mediated TLR3 activation in macrophage innate immunity against HIV.

  13. Salton Sea Scientific Drilling Project: A summary of drilling and engineering activities and scientific results

    SciTech Connect

    Ross, H.P.; Forsgren, C.K.

    1992-04-01

    The Salton Sea Scientific g Project (SSSDP) completed the first major well in the United States Continental Scientific Drilling Program. The well (State 2-14) was drilled to 10,W ft (3,220 m) in the Salton Sea Geothermal Field in California's Imperial Valley, to permit scientific study of a deep, high-temperature portion of an active geothermal system. The program was designed to investigate, through drilling and testing, the subsurface thermal, chemical, and mineralogical environments of this geothermal area. Extensive samples and data, including cores, cuttings, geothermal fluids and gases, and geophysical logs, were collected for future scientific analysis, interpretation, and publication. Short duration flow tests were conducted on reservoirs at a depth of approximately 6,120 ft (1,865 m) and at 10,136 ft (3,089 m). This report summarizes all major activities of the SSSDP, from project inception in the fall of 1984 through brine-pond cleanup and site restoration, ending in February 1989. This report presents a balanced summary of drilling, coring, logging, and flow-test operations, and a brief summary of technical and scientific results. Frequent reference is made to original records, data, and publication of results. The report also reviews the proposed versus the final well design, and operational summaries, such as the bit record, the casing and cementing program, and the coring program. Summaries are and the results of three flow tests. Several teamed during the project.

  14. Results from the Nuclear Plant Aging Research Program: Their use in inspection activities

    SciTech Connect

    Gunther, W.; Taylor, J. )

    1990-09-01

    The US NCR's Nuclear Plant Aging Research (NPAR) Program has determined the susceptibility to aging of components and systems, and the potential for aging to impact plant safety and availability. The NPAR Program also identified methods for detecting and mitigating aging in components. This report describes the NPAR results which can enhance NRC inspection activities. Recommendations are provided for communicating pertinent information to NRC inspectors. These recommendations are based on a detailed assessment of the NRC's Inspection Program, and feedback from resident and regional inspectors as described within. Examples of NPAR report summaries and aging inspection guides for components and systems are included. 13 refs., 3 figs., 4 tabs.

  15. Video and film analysis with correlation tracking and active result presentation (Abstract Only)

    NASA Astrophysics Data System (ADS)

    Rowa, Per

    1990-08-01

    Experience with a turnkey analysis system featuring high resolution video input and display, a modular video disc system and a 16 mm cine film scanner with 2600-point resolution, is presented. Tracking is performed with a high-speed correlation process, requiring no special markers. Software packages for evaluating two and three-dimensional results are interactively accessible. Combining the original image sequence with real-time graphic overlays and active drawing of graphic diagrams, provides for an excellent understanding and documentation of the motion sequences.

  16. The working group ``Science with the SRT'': tasks, activities, and results

    NASA Astrophysics Data System (ADS)

    Prandoni, I.; Felli, M.

    The Working Group Science with the SRT was formed in May 2004, with the aim of providing scientific input to the Board of the SRT, in order to plan the focal plane instrumentation development of the SRT. In the present contribution, tasks and activities of the Working Group are outlined, and the main indications and results are briefly summarized. For a detailed discussion we refer to the IRA Internal Report ``The Sardinia Radio Telescope (SRT). Science and Technical Requirements'' produced by the members of the Working Group.

  17. The Formation of CIRs at Stream-Stream Interfaces and Resultant Geomagnetic Activity

    NASA Technical Reports Server (NTRS)

    Richardson, I. G.

    2005-01-01

    Corotating interaction regions (CIRs) are regions of compressed plasma formed at the leading edges of corotating high-speed solar wind streams originating in coronal holes as they interact with the preceding slow solar wind. Although particularly prominent features of the solar wind during the declining and minimum phases of the 11-year solar cycle, they may also be present at times of higher solar activity. We describe how CIRs are formed, and their geomagnetic effects, which principally result from brief southward interplanetary magnetic field excursions associated with Alfven waves. Seasonal and long-term variations in these effects are briefly discussed.

  18. Active vibration absorber for the CSI evolutionary model - Design and experimental results. [Controls Structures Interaction

    NASA Technical Reports Server (NTRS)

    Bruner, Anne M.; Belvin, W. Keith; Horta, Lucas G.; Juang, Jer-Nan

    1991-01-01

    The development of control of large flexible structures technology must include practical demonstrations to aid in the understanding and characterization of controlled structures in space. To support this effort, a testbed facility has been developed to study practical implementation of new control technologies under realistic conditions. The paper discusses the design of a second order, acceleration feedback controller which acts as an active vibration absorber. This controller provides guaranteed stability margins for collocated sensor/actuator pairs in the absence of sensor/actuator dynamics and computational time delay. Experimental results in the presence of these factors are presented and discussed. The robustness of this design under model uncertainty is demonstrated.

  19. Fluctuations and resulting competing pathways in RNA folding: The activation of splicing

    NASA Astrophysics Data System (ADS)

    Fernández, Ariel

    1991-01-01

    We implement a parallel processing Monte Carlo simulation to explore RNA configuration space that takes into account fluctuations in base-pairing patterns. The choice of folding pathways is biased by the refolding events that occur as the chain is being assembled. We prove that fluctuations in the initial stages of folding might lead to either active or inactive emerging structures. As an illustration, competing pathways that are the result of fluctuation propagation are computed for the splicing YC4 intron (a segment of the mitochondrial RNA from fungi), and the emerging structures are proved to be biologically relevant.

  20. Charpy impact test results for low activation ferritic alloys irradiated to 30 dpa

    SciTech Connect

    Schubert, L.E.; Hamilton, M.L.; Gelles, D.S.

    1996-04-01

    Miniature specimens of six low activation ferritic alloys have been impact field tested following irradiation at 370{degrees}C to 30 dpa. Comparison of the results with those of control specimens and specimens irradiated to 10 dpa indicates that degradation in the impact behavior appears to have saturated by {approx}10 dpa in at least four of these alloys. The 7.5Cr-2W alloy referred to as GA3X appears most promising for further consideration as a candidate structural material in fusion reactor applications, although the 9Cr-1V alloy may also warrant further investigation.

  1. Field Test Results from a 10 kW Wind Turbine with Active Flow Control

    NASA Astrophysics Data System (ADS)

    Rice, Thomas; Bychkova, Veronika; Taylor, Keith; Clingman, Dan; Amitay, Michael

    2015-11-01

    Active flow control devices including synthetic jets and dynamic vortex generators were tested on a 10 kW wind turbine at RPI. Previous work has shown that load oscillations caused by dynamic stall could be modified through the use of active flow control by injecting momentum into the flow field near the leading edge of a dynamically pitching model. In this study, this work has been extended to its logical conclusion, field-testing active flow control on a real wind turbine. The blades in the current study have a 0.28m chord and 3.05m span, no twist or taper, and were retrofitted with six synthetic jets on one blade and ten dynamic vortex generators on a second blade. The third blade of this turbine was not modified, in order to serve as a control. Strain gauges were installed on each blade to measure blades' deflection. A simple closed loop control was demonstrated and preliminary results indicate reduced vibrational amplitude. Future testing will be conducted on a larger scale, 600kW machine at NREL, incorporating information collected during this study.

  2. The smelling of Hedione results in sex-differentiated human brain activity.

    PubMed

    Wallrabenstein, I; Gerber, J; Rasche, S; Croy, I; Kurtenbach, S; Hummel, T; Hatt, H

    2015-06-01

    A large family of vomeronasal receptors recognizes pheromone cues in many animals including most amphibia, reptiles, rhodents, and other mammals. Humans possess five vomeronasal-type 1 receptor genes (VN1R1-VN1R5), which code for proteins that are functional in recombinant expression systems. We used two different recombinant expression systems and identified Hedione as a ligand for the putative human pheromone receptor VN1R1 expressed in the human olfactory mucosa. Following the ligand identification, we employed functional magnetic resonance imaging (fMRI) in healthy volunteers to characterize the in vivo action of the VN1R1 ligand Hedione. In comparison to a common floral odor (phenylethyl alcohol), Hedione exhibited significantly enhanced activation in limbic areas (amygdala, hippocampus) and elicited a sex-differentiated response in a hypothalamic region that is associated with hormonal release. Utilizing a novel combination of methods, our results indicate that the putative human pheromone receptor VN1R1 is involved in extra-olfactory neuronal activations induced by the odorous substance Hedione. The activation of VN1R1 might play a role in gender-specific modulation of hormonal secretion in humans.

  3. Nighttime instabilities of neurophysiological, cardiovascular, and respiratory activity: integrative modeling and preliminary results

    PubMed Central

    Shusterman, Vladimir; Troy, William C.; Abdelmessih, Medhat; Hoffman, Stacy; Nemec, Jan; Strollo, Patrick J.; London, Barry; Lampert, Rachel

    2015-01-01

    Unstable (cyclical alternating pattern, or CAP) sleep is associated with surges of sympathetic nervous system activity, increased blood pressure and vasoconstriction, heightened baroreflex sensitivity, and unstable heart rhythm and breathing. In susceptible persons, CAP sleep provokes clinically significant events, including hypertensive crises, sleep-disordered breathing, and cardiac arrhythmias. Here we explore the neurophysiology of CAP sleep and its impact on cardiovascular and respiratory functions. We show that: (i) an increase in neurophysiological recovery rate can explain the emergence of slow, self-sustained, hypersynchronized A1 CAP-sleep pattern and its transition to the faster A2-A3 CAP-sleep patterns; (ii) in a two-dimensional, continuous model of cardiac tissue with heterogeneous action potential duration (APD) distribution, heart rate accelerations during CAP sleep may encounter incompletely recovered electrical excitability in cell clusters with longer APD. If the interaction between short cycle length and incomplete, spatially heterogeneous repolarization persists over multiple cycles, irregularities and asymmetry of depolarization front may accumulate and ultimately lead to a conduction block, retrograde conduction, breakup of activation waves, reentrant activity, and arrhythmias; and (iii) these modeling results are consistent with the nighttime data obtained from patients with structural heart disease (N=13) that show clusters of atrial and ventricular premature beats occurring during the periods of unstable heart rhythm and respiration that accompany CAP sleep. In these patients, CAP sleep is also accompanied by delayed adaptation of QT intervals and T-wave alternans. PMID:26341647

  4. Regional distribution pattern of groundwater heavy metals resulting from agricultural activities

    NASA Astrophysics Data System (ADS)

    Nouri, J.; Mahvi, A. H.; Jahed, G. R.; Babaei, A. A.

    2008-09-01

    Contaminations of groundwater by heavy metals due to agricultural activities are growing recently. The objective of this study was to evaluate and map regional patterns of heavy metals (Cd, Zn and Cu) in groundwater on a plain with high agricultural activities. The study was conducted to investigate the concentration of heavy metals and distribution in groundwater in regions of Shush Danial and Andimeshk aquifers in the southern part of Iran. Presently, groundwater is the only appropriate and widely used source of drinking water for rural and urban communities in this region. The region covers an area of 1,100 km2 between the Dez and Karkhe rivers, which lead to the Persian Gulf. For this study, the region was divided into four sub-regions A, B, C and D. Additionally, 168 groundwater samples were collected from 42 water wells during the earlier months of 2004. The flame atomic absorption spectrometry (AAS-Flame) was used to measure the concentration of heavy metals in water samples and the Surfer software was used for determination of the contour map of metal distribution. The results demonstrated that in all of the samples, Cd and Zn concentrations were below the EPA MCLG and EPA secondary standard, respectively. However, the Cu contents of 4.8 % of all samples were higher than EPA MCL. It is also indicated that the concentrations of metals were more pronounced at the southern part of the studied region than at the others. The analysis of fertilizers applied for agricultural activities at this region also indicated that a great majority of the above-mentioned heavy metals were discharged into the environment. Absence of confining layers, proximity to land surface, excess agricultural activities in the southern part and groundwater flow direction that is generally from the north to the southern parts in this area make the southern region of the Shush plain especially vulnerable to pollution by heavy metals than by other contaminants.

  5. Hypouricaemic action of mangiferin results from metabolite norathyriol via inhibiting xanthine oxidase activity.

    PubMed

    Niu, Yanfen; Liu, Jia; Liu, Hai-Yang; Gao, Li-Hui; Feng, Guo-Hua; Liu, Xu; Li, Ling

    2016-09-01

    Context Mangiferin has been reported to possess a potential hypouricaemic effect. However, the pharmacokinetic studies in rats showed that its oral bioavailability was only 1.2%, suggesting that mangiferin metabolites might exert the action. Objective The hypouricaemic effect and the xanthine oxidase inhibition of mangiferin and norathyriol, a mangiferin metabolite, were investigated. Inhibition of norathyriol analogues (compounds 3-9) toward xanthine oxidase was also evaluated. Materials and methods For a dose-dependent study, mangiferin (1.5-6.0 mg/kg) and norathyriol (0.92-3.7 mg/kg) were administered intragastrically to mice twice daily for five times. For a time-course study, mice received mangiferin and norathyriol both at a single dose of 7.1 μmol/kg. In vitro, inhibition of test compounds (2.4-2.4 mM) against xanthine oxidase activity was evaluated by the spectrophotometrical method. The inhibition type was identified from Lineweaver-Burk plots. Results Norathyriol (0.92, 1.85 and 3.7 mg/kg) dose dependently decreased the serum urate levels by 27.0, 33.6 and 37.4%, respectively. The action was more potent than that of mangiferin at the low dose, but was equivalent at the higher doses. Additionally, the hypouricaemic action of them exhibited a time dependence. In vitro, norathyriol markedly inhibited the xanthine oxidase activities, with the IC50 value of 44.6 μM, but mangiferin did not. The kinetic studies showed that norathyriol was an uncompetitive inhibitor by Lineweaver-Burk plots. The structure-activity relationships exhibited that three hydroxyl groups in norathyriol at the C-1, C-3 and C-6 positions were essential for maintaining xanthine oxidase inhibition. Discussion and conclusion Norathyriol was responsible for the hypouricaemic effect of mangiferin via inhibiting xanthine oxidase activity.

  6. The status of the CABRI test program: Recent results and future activities

    SciTech Connect

    Schmitz, F.; Gonnier, Ch.; Papin, J.

    1997-01-01

    The first five CABRI experiments of the REP-Na series, all with UO2 fuel and up to a maximum local burnup of 64 GWd/t, have been examined and analyzed and are now reasonably well understood. In March 1996, the first MOX test with a 3 cycle irradiated fuel at 47 GWd/t radially averaged, local maximum burnup has been successfully performed. The rod did not fail and detailed examinations are being obtained and still in progress presently. The available results and findings are presented in this paper. Three experiments of the REP-Na test matrix are still to be performed, REP-Na7, a 4 cycle MOX test, is scheduled in November 1996. The last two experiments, REP-Na 8 the key experiment of the UO2 matrix, and REP-Na 9, a 2 cycle MOX fuel test, will be performed during the first half of 1997. The CABRI tests made with sodium cooling have a good representativity of reactor conditions during some tens of milliseconds. For better simulation on a longer time range, a project study has been undertaken in view of the implementation of a pressurized-water loop into the CABRI reactor. The design of this loop and the performance parameters of the upgraded driver core of CABRI is presented. Finally, the planning of the CABRI transformation and the outlines of the future test matrix is given. The most optimistic estimation allows to predict that the first tests under prototypical test conditions could be performed before the end of 1999.

  7. Understanding Active Galactic Nuclei using near-infrared high angular resolution polarimetry II: Preliminary results

    NASA Astrophysics Data System (ADS)

    Marin, F.; Grosset, L.; Goosmann, R.; Gratadour, D.; Rouan, D.; Clénet, Y.; Pelat, D.; Rojas Lobos, P. A.

    2016-12-01

    In this second research note of a series of two, we present the first near-infrared results we obtained when modeling Active Galactic Nuclei (AGN). Our first proceedings showed the comparison between the MontAGN and STOKES Monte Carlo codes. Now we use our radiative transfer codes to simulate the polarization maps of a prototypical, NGC 1068-like, type-2 radio-quiet AGN. We produced high angular resolution infrared (1 μm) polarization images to be compared with recent observations in this wavelength range. Our preliminary results already show a good agreement between the models and observations but cannot account for the peculiar linear polarization angle of the torus such as observed. tet{Gratadour2015} found a polarization position angle being perpendicular to the bipolar outflows axis. Further work is needed to improve the models by adding physical phenomena such as dichroism and clumpiness.

  8. Carbon fiber composites inspection and defect characterization using active infrared thermography: numerical simulations and experimental results.

    PubMed

    Fernandes, Henrique; Zhang, Hai; Figueiredo, Alisson; Ibarra-Castanedo, Clemente; Guimarares, Gilmar; Maldague, Xavier

    2016-12-01

    Composite materials are widely used in the aeronautic industry. One of the reasons is because they have strength and stiffness comparable to metals, with the added advantage of significant weight reduction. Infrared thermography (IT) is a safe nondestructive testing technique that has a fast inspection rate. In active IT, an external heat source is used to stimulate the material being inspected in order to generate a thermal contrast between the feature of interest and the background. In this paper, carbon-fiber-reinforced polymers are inspected using IT. More specifically, carbon/PEEK (polyether ether ketone) laminates with square Kapton inserts of different sizes and at different depths are tested with three different IT techniques: pulsed thermography, vibrothermography, and line scan thermography. The finite element method is used to simulate the pulsed thermography experiment. Numerical results displayed a very good agreement with experimental results.

  9. Multi-object active shape model construction for abdomen segmentation: preliminary results.

    PubMed

    Gollmer, Sebastian T; Simon, Martin; Bischof, Arpad; Barkhausen, Jorg; Buzug, Thorsten M

    2012-01-01

    The automatic segmentation of abdominal organs is a pre-requisite for many medical applications. Successful methods typically rely on prior knowledge about the to be segmented anatomy as it is for instance provided by means of active shape models (ASMs). Contrary to most previous ASM based methods, this work does not focus on individual organs. Instead, a more holistic approach that aims at exploiting inter-organ relationships to eventually segment a complex of organs is proposed. Accordingly, a flexible framework for automatic construction of multi-object ASMs is introduced, employed for coupled shape modeling, and used for co-segmentation of liver and spleen based on a new coupled shape/separate pose approach. Our first results indicate feasible segmentation accuracies, whereas pose decoupling leads to substantially better segmentation results and performs in average also slightly better than the standard single-object ASM approach.

  10. First experimental results on active and slim-edge silicon sensors for XFEL

    NASA Astrophysics Data System (ADS)

    Pancheri, L.; Benkechcache, M. E. A.; Dalla Betta, G.-F.; Xu, H.; Verzellesi, G.; Ronchin, S.; Boscardin, M.; Ratti, L.; Grassi, M.; Lodola, L.; Malcovati, P.; Vacchi, C.; Manghisoni, M.; Re, V.; Traversi, G.; Batignani, G.; Bettarini, S.; Casarosa, G.; Giorgi, M.; Forti, F.; Paladino, A.; Paoloni, E.; Rizzo, G.; Morsani, F.; Fabris, L.

    2016-12-01

    This work presents the first characterization results obtained on a pilot fabrication run of planar sensors, tailored for X-ray imaging applications at FELs, developed in the framework of INFN project PixFEL. Active and slim-edge p-on-n sensors are fabricated on n-type high-resistivity silicon with 450 μm thickness, bonded to a support wafer. Both diodes and pixelated sensors with a pitch of 110 μm are included in the design. Edge structures with different number of guard rings are designed to comply with the large bias voltage required by the application after accumulating an ionizing radiation dose as large as 1GGy. Preliminary results from the electrical characterization of the produced sensors, providing a first assessment of the proposed approach, are discussed. A functional characterization of the sensors with a pulsed infrared laser is also presented, demonstrating the validity of slim-edge configurations.

  11. Immune Activation Resulting from NKG2D/Ligand Interaction Promotes Atherosclerosis

    PubMed Central

    Xia, Mingcan; Guerra, Nadia; Sukhova, Galina K.; Yang, Kangkang; Miller, Carla K.; Shi, Guo-Ping; Raulet, David H.; Xiong, Na

    2012-01-01

    Background The interplay between the immune system and abnormal metabolic conditions sustains and propagates a vicious feedback cycle of chronic inflammation and metabolic dysfunction that is critical for atherosclerotic progression. It is well established that abnormal metabolic conditions, such as dyslipidemia and hyperglycemia, cause various cellular stress responses that induce tissue inflammation and immune cell activation, which in turn exacerbate the metabolic dysfunction. However, molecular events linking these processes are not well understood. Methods and Results Tissues and organs of humans and mice with hyperglycemia and hyperlipidemia were examined for expression of ligands for NKG2D, a potent immune activating receptor expressed by several types of immune cells, and the role of NKG2D in atherosclerosis and metabolic diseases was probed using mice lacking NKG2D or by blocking NKG2D with monoclonal antibodies. NKG2D ligands were upregulated in multiple organs, particularly atherosclerotic aortae and inflamed livers. Ligand upregulation was induced in vitro by abnormal metabolites associated with metabolic dysfunctions. Using ApoE-/- mouse models we demonstrated that preventing NKG2D functions resulted in a dramatic reduction in plaque formation, suppressed systemic and organ inflammation mediated by multiple immune cell types, and alleviated abnormal metabolic conditions. Conclusions The NKG2D/ligand interaction is a critical molecular link in the vicious cycle of chronic inflammation and metabolic dysfunction that promotes atherosclerosis and might be a useful target for therapeutic intervention in the disease. PMID:22104546

  12. High fat diet feeding results in gender specific steatohepatitis and inflammasome activation

    PubMed Central

    Ganz, Michal; Csak, Timea; Szabo, Gyongyi

    2014-01-01

    AIM: To develop an animal model that encompasses the different facets of non-alcoholic steatohepatitis (NASH), which has been a challenge. METHODS: In this study, we used a high fat diet (HFD) feeding supplemented with fructose and sucrose in the water mimicking the high-fructose corn syrup that is abundant in the diet in the United States. We used C57Bl/6 wild-type mice for short and long-term feedings of 6 and 16 wk respectively, and evaluated the extent of liver damage, steatosis, and inflammasome activation. Our methods included histopathological analysis to assess liver damage and steatosis, which involved H and E and oil-red-o staining; biochemical studies to look at ALT and triglyceride levels; RNA analysis using quantitative polymerase chain reaction; and cytokine analysis, which included the enzyme-linked immunosorbent assay method to look at interleukin (IL)-1β and tumor necrosis factor-α (TNFα) levels. Furthermore, at each length of feeding we also looked at insulin resistance and glucose tolerance using insulin tolerance tests (ITT) and glucose tolerance tests. RESULTS: There was no insulin resistance, steatosis, or inflammasome activation at 6 wk. In contrast, at 16 wk we found significant insulin resistance demonstrated by impaired glucose and ITT in male, but not female mice. In males, elevated alanine aminotransferase and triglyceride levels, indicated liver damage and steatosis, respectively. Increased liver TNFα and monocyte chemoattractant protein-1 mRNA and protein, correlated with steatohepatitis. The inflammasome components, adaptor molecule, Aim2, and NOD-like receptor 4, increased at the mRNA level, and functional inflammasome activation was indicated by increased caspase-1 activity and IL-1β protein levels in male mice fed a long-term HFD. Male mice on HFD had increased α-smooth muscle actin and pro-collagen-1 mRNA indicating evolving fibrosis. In contrast, female mice displayed only elevated triglyceride levels, steatosis, and no

  13. Antineoplastic activity of povidone-iodine on different mesothelioma cell lines: results of in vitro study†

    PubMed Central

    Fiorelli, Alfonso; Pentimalli, Francesca; D'Urso, Vittorio; Di Marzo, Domenico; Forte, Iris Maria; Giordano, Antonio; Di Domenico, Marina; Accardo, Marina; Di Serio, Umberto; Santini, Mario

    2014-01-01

    OBJECTIVE Povidone-iodine (PVP-I) or Betadine, owing to its antineoplastic activity, is also used as an adjuvant during intra-abdominal or intrathoracic surgery. However, the protocol of PVP-I administration has not been optimized to achieve the best antitumoural efficacy. We aimed to determine the optimal concentration of PVP-I, the time of incubation and the mechanism of cell death by analysing the effect of different doses and time of administration of PVP-I on the cell viability of different mesothelioma cell lines. METHODS Four different cell lines (MET 5A/normal mesothelium; H2052/sarcomatoid mesothelioma; ISTMES2/epithelial mesothelioma; MSTO/biphasic mesothelioma) were incubated with increasing concentrations of diluted PVP-I (0.0001; 0.001; 0.01; 0.1; 1%) for 5, 10, 30, 60 min and 24 h, respectively. Cell viability was determined using cell direct cytotoxicity assay and cell death was determined through flow cytometry assay analysis. The superoxide dismutase activity was assessed functionally through a specific inhibitor to evaluate the mechanism of cell death. RESULTS The antiproliferative effect of PVP-I varied largely among different cell lines in a dose- and time-dependent manner. At 0.1% concentration for 10 min of incubation, the percentage of viable cells was 0.5 ± 0.1; 0.8 ± 0.5 and 0% (P < 0.01) for MET5A, ISTMES2 and MSTO, respectively. Conversely, the same concentration did not significantly affect the H2052 cell line which was completely suppressed at a 1% concentration of PVP-I. Double staining of Annexin V and DNA showed that PVP-I induced cell death in all four cell lines via necrosis depending on PVP-I concentration. However, H2052 was found to be more resistant than MSTO, ISTMES2 and MET 5A cells lines. The activity of superoxide dismutase was significantly inhibited in all cell lines. CONCLUSIONS Our results confirmed the anti-neoplastic activity of PVP-I especially on ISTMES2 and MSTO cell lines. With respect to chemotherapy pleural

  14. Cryptographic Key Management System

    SciTech Connect

    No, author

    2014-02-21

    This report summarizes the outcome of U.S. Department of Energy (DOE) contract DE-OE0000543, requesting the design of a Cryptographic Key Management System (CKMS) for the secure management of cryptographic keys for the energy sector infrastructure. Prime contractor Sypris Electronics, in collaboration with Oak Ridge National Laboratories (ORNL), Electric Power Research Institute (EPRI), Valicore Technologies, and Purdue University's Center for Education and Research in Information Assurance and Security (CERIAS) and Smart Meter Integration Laboratory (SMIL), has designed, developed and evaluated the CKMS solution. We provide an overview of the project in Section 3, review the core contributions of all contractors in Section 4, and discuss bene ts to the DOE in Section 5. In Section 6 we describe the technical construction of the CKMS solution, and review its key contributions in Section 6.9. Section 7 describes the evaluation and demonstration of the CKMS solution in different environments. We summarize the key project objectives in Section 8, list publications resulting from the project in Section 9, and conclude with a discussion on commercialization in Section 10 and future work in Section 11.

  15. Update of the BIPM comparison BIPM.RI(II)-K1.Cs-134 of activity measurements of the radionuclide 134Cs to include the 2008 results of the BEV (Austria), the 2009 result of the IRA (Switzerland) and the 2010 results of the NMISA (South Africa)

    NASA Astrophysics Data System (ADS)

    Michotte, C.; Ratel, G.; Courte, S.; Maringer, F. J.; Caffari, Y.; van Wyngaardt, W. M.

    2013-01-01

    Since 2008, three national metrology institutes have submitted ampoules for the measurement of 134Cs in the International Reference System (SIR). The values of the activity submitted were between about 0.17 MBq and 2.3 MBq. The primary standardization result for the IRA, Switzerland, replaces their earlier result of 1978 but no change is proposed for the key comparison reference value at the present time. There are now 14 results in the BIPM.RI(II)-K1.Cs-134 comparison. Main text. To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  16. Alteration of rare earth element distribution as a result of microbial activity and empirical methane injection

    NASA Astrophysics Data System (ADS)

    Castillo, D. J.; Davies, N. W.; Thurber, A. R.; Haley, B. A.; Colwell, F. S.

    2014-12-01

    As a result of warming, methane is being released into the marine environment in areas that have not historically experienced methane input. While methane is a potent greenhouse gas, microbial oxidation of methane within the sediment greatly limits the role of marine methane sources on atmospheric forcing. However, in these areas of new methane release, consumption of methane prior to its release into the atmosphere is a result of the response of the microbial community to this new input of methane. Further, rare earth elements (REEs) are not currently thought to be involved with microbial activity, but this assumption has not been rigorously tested. Here we test that: (1) microbial communities will rapidly respond to the onset of methane emission, and (2) the microbial response to this methane input will impact the distribution of REEs within the sediment. Undisturbed cores sampled from a tidal flat at Yaquina Bay, OR, were brought back to a lab and injected with anoxic seawater (as a control) or anoxic sea water saturated with methane gas for a total of 2 weeks. Aerobic methanotrophs proliferated over this short time period, becoming an abundant member of the microbial community as identified using fatty acid biomarkers. Excitingly, the experimental injection of methane also shifted the distribution of REEs within the sediment, a trend that appeared to follow the microbial response and that was different from the control cores. Further, the lightest REEs appeared to be used more than the heavier ones, supporting that the REEs are being actively used by the microbes. While we focused on identifying the response of those microbes responsible in methane-cycling, we also identified how the entire microbial community shifts as a result of methane input, and correlating with shifts in REE distribution. Here we have empirically demonstrated the rapid response of methanotrophs to the onset of methane emission and that REE distribution within the sediment is likely

  17. Update of the BIPM comparison BIPM.RI(II)-K1.Co-60 of activity measurements of the radionuclide 60Co to include the 2011 result of the CNEA (Argentina), the 2012 results of the BARC (India) and the NRC (Canada), and the 2014 result of the NIM (China)

    NASA Astrophysics Data System (ADS)

    Michotte, C.; Ratel, G.; Courte, S.; Arenillas, P.; Balpardo, C.; Joseph, L.; Anuradha, R.; Kulkarni, D. B.; Galea, R.; Moore, K.; Stroak, A.; Zhang, Ming; Liang, Juncheng; Liu, Haoran

    2017-01-01

    Since 2010, four national metrology institutes (NMI) have each submitted a sample of known activity of 60Co to the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures (BIPM), with comparison identifier BIPM.RI(II)-K1.Co-60. The values of the activity submitted were between about 175 kBq and 1600 kBq. The primary standardization results for the CNEA, Argentina and the BARC, India replace their earlier result of 2003 and 2001, respectively. There are now seventeen results in the BIPM.RI(II)-K1.Co-60 comparison. The key comparison reference value (KCRV) has been updated using the power-moderated weighted mean. The degrees of equivalence between each equivalent activity measured in the SIR and the KCRV have been calculated and the results are given in the form of a table. A graphical presentation is also given. Main text To reach the main text of this paper, click on Final Report. Note that this text is that which appears in Appendix B of the BIPM key comparison database kcdb.bipm.org/. The final report has been peer-reviewed and approved for publication by the CCRI, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  18. Youth Civic Engagement in China: Results from a Program Promoting Environmental Activism

    ERIC Educational Resources Information Center

    Johnson, Laura R.; Johnson-Pynn, Julie S.; Pynn, Thomas M.

    2007-01-01

    China is a key player on the global stage, and nearly 300 million Chinese youth stand to be affected by rapid social and ecological transformations. Programs that promote developmental assets in Chinese youth could increase their resilience in the face of contemporary stressors and enhance their capacity to contribute to China's development. In…

  19. Twist Model Development and Results from the Active Aeroelastic Wing F/A-18 Aircraft

    NASA Technical Reports Server (NTRS)

    Lizotte, Andrew M.; Allen, Michael J.

    2007-01-01

    Understanding the wing twist of the active aeroelastic wing (AAW) F/A-18 aircraft is a fundamental research objective for the program and offers numerous benefits. In order to clearly understand the wing flexibility characteristics, a model was created to predict real-time wing twist. A reliable twist model allows the prediction of twist for flight simulation, provides insight into aircraft performance uncertainties, and assists with computational fluid dynamic and aeroelastic issues. The left wing of the aircraft was heavily instrumented during the first phase of the active aeroelastic wing program allowing deflection data collection. Traditional data processing steps were taken to reduce flight data, and twist predictions were made using linear regression techniques. The model predictions determined a consistent linear relationship between the measured twist and aircraft parameters, such as surface positions and aircraft state variables. Error in the original model was reduced in some cases by using a dynamic pressure-based assumption. This technique produced excellent predictions for flight between the standard test points and accounted for nonlinearities in the data. This report discusses data processing techniques and twist prediction validation, and provides illustrative and quantitative results.

  20. Twist Model Development and Results From the Active Aeroelastic Wing F/A-18 Aircraft

    NASA Technical Reports Server (NTRS)

    Lizotte, Andrew; Allen, Michael J.

    2005-01-01

    Understanding the wing twist of the active aeroelastic wing F/A-18 aircraft is a fundamental research objective for the program and offers numerous benefits. In order to clearly understand the wing flexibility characteristics, a model was created to predict real-time wing twist. A reliable twist model allows the prediction of twist for flight simulation, provides insight into aircraft performance uncertainties, and assists with computational fluid dynamic and aeroelastic issues. The left wing of the aircraft was heavily instrumented during the first phase of the active aeroelastic wing program allowing deflection data collection. Traditional data processing steps were taken to reduce flight data, and twist predictions were made using linear regression techniques. The model predictions determined a consistent linear relationship between the measured twist and aircraft parameters, such as surface positions and aircraft state variables. Error in the original model was reduced in some cases by using a dynamic pressure-based assumption and by using neural networks. These techniques produced excellent predictions for flight between the standard test points and accounted for nonlinearities in the data. This report discusses data processing techniques and twist prediction validation, and provides illustrative and quantitative results.

  1. Peptide modification results in the formation of a dimer with a 60-fold enhanced antimicrobial activity

    PubMed Central

    Thamri, Amal; Létourneau, Myriam; Djoboulian, Alex; Chatenet, David; Déziel, Eric; Perreault, Jonathan

    2017-01-01

    Cationic antimicrobial peptides (CAMPs) occur naturally in numerous organisms and are considered as a class of antibiotics with promising potential against multi-resistant bacteria. Herein, we report a strategy that can lead to the discovery of novel small CAMPs with greatly enhanced antimicrobial activity and retained antibiofilm potential. We geared our efforts towards i) the N-terminal cysteine functionalization of a previously reported small synthetic cationic peptide (peptide 1037, KRFRIRVRV-NH2), ii) its dimerization through a disulfide bond, and iii) a preliminary antimicrobial activity assessment of the newly prepared dimer against Pseudomonas aeruginosa and Burkholderia cenocepacia, pathogens responsible for the formation of biofilms in lungs of individuals with cystic fibrosis. This dimer is of high interest as it does not only show greatly enhanced bacterial growth inhibition properties compared to its pep1037 precursor (up to 60 times), but importantly, also displays antibiofilm potential at sub-MICs. Our results suggest that the reported dimer holds promise for its use in future adjunctive therapy, in combination with clinically-relevant antibiotics. PMID:28296935

  2. Increases in Physical Activity Result in Diminishing Increments in Daily Energy Expenditure in Mice.

    PubMed

    O'Neal, Timothy J; Friend, Danielle M; Guo, Juen; Hall, Kevin D; Kravitz, Alexxai V

    2017-02-06

    Exercise is a common component of weight loss strategies, yet exercise programs are associated with surprisingly small changes in body weight [1-4]. This may be due in part to compensatory adaptations, in which calories expended during exercise are counteracted by decreases in other aspects of energy expenditure [1, 5-10]. Here we examined the relationship between a rodent model of voluntary exercise- wheel running- and total daily energy expenditure. Use of a running wheel for 3 to 7 days increased daily energy expenditure, resulting in a caloric deficit of ∼1 kcal/day; however, total daily energy expenditure remained stable after the first week of wheel access, despite further increases in wheel use. We hypothesized that compensatory mechanisms accounted for the lack of increase in daily energy expenditure after the first week. Supporting this idea, we observed a decrease in off-wheel ambulation when mice were using the wheels, indicating behavioral compensation. Finally, we asked whether individual variation in wheel use within a group of mice would be associated with different levels of daily energy expenditure. Despite a large variation in wheel running, we did not observe a significant relationship between the amount of daily wheel running and total daily energy expenditure or energy intake across mice. Together, our experiments support a model in which the transition from sedentary to light activity is associated with an increase in daily energy expenditure, but further increases in physical activity produce diminishingly small increments in daily energy expenditure.

  3. Experimentally activated immune defence in female pied flycatchers results in reduced breeding success.

    PubMed

    Ilmonen, P; Taarna, T; Hasselquist, D

    2000-04-07

    Traditional explanations for the negative fitness consequences of parasitism have focused on the direct pathogenic effects of infectious agents. However, because of the high selection pressure by the parasites, immune defences are likely to be costly and trade off with other fitness-related traits, such as reproductive effort. In a field experiment, we immunized breeding female flycatchers with non-pathogenic antigens (diphtheria-tetanus vaccine), which excluded the direct negative effects of parasites, in order to test the consequences of activated immune defence on hosts' investment in reproduction and self-maintenance. Immunized females decreased their feeding effort and investment in self-maintenance (rectrix regrowth) and had lower reproductive output (fledgling quality and number) than control females injected with saline. Our results reveal the phenotypic cost of immune defence by showing that an activated immune system per se can lower the host's breeding success. This may be caused by an energetic or nutritional trade-off between immune function and physical workload when feeding young or be an adaptive response to 'infection' to avoid physiological disorders such as oxidative stress and immunopathology.

  4. Optimal placement of piezoelectric plates for active vibration control of gas turbine blades: experimental results

    NASA Astrophysics Data System (ADS)

    Botta, F.; Marx, N.; Gentili, S.; Schwingshackl, C. W.; Di Mare, L.; Cerri, G.; Dini, D.

    2012-04-01

    It is well known that the gas turbine blade vibrations can give rise to catastrophic failures and a reduction of the blades life because of fatigue related phenomena[1]-[3] . In last two decades, the adoption of piezoelectric elements, has received considerable attention by many researcher for its potential applicability to different areas of mechanical, aerospace, aeronautical and civil engineering. Recently, a number of studies of blades vibration control via piezoelectric plates and patches have been reported[4]-[6] . It was reported that the use of piezoelectric elements can be very effective in actively controlling vibrations. In one of their previous contributions[7] , the authors of the present manuscript studied a model to control the blade vibrations by piezoelectric elements and validated their results using a multi-physics finite elements package (COMSOL) and results from the literature. An optimal placement method of piezoelectric plate has been developed and applied to different loading scenarios for realistic configurations encountered in gas turbine blades. It has been demonstrated that the optimal placement depends on the spectrum of the load, so that segmented piezoelectric patches have been considered and, for different loads, an optimal combination of sequential and/or parallel actuation and control of the segments has been studied. In this paper, an experimental investigation carried out by the authors using a simplified beam configuration is reported and discussed. The test results obtained by the investigators are then compared with the numerical predictions [7] .

  5. New Activity of Chiron: Results from 5 Years of Photometric Monitoring

    NASA Astrophysics Data System (ADS)

    Duffard, René; Lazzaro, Daniela; Pinto, Sandro; Carvano, Jorge; Angeli, Claudia; Alvarez-Candal, Alvaro; Fernández, Silvia

    2002-11-01

    The results of photometric observations of Centaur object Chiron carried out at the Observatório do Pico dos Dias (OPD, Brazil), the Estación Astrofı´sica de Bosque Alegre (EABA, Argentina), and Complejo Astronómico El Leoncito (CASLEO, Argentina) from 1997 to 2001 are presented here. The analysis of the photometric data shows that the brightness of Chiron reached a minimum value in 1999 and began increasing again in 2000. The absolute magnitude, HV, varied from 7.26 in June 1999 to 5.78 in April 2001. The data tend to indicate that Chiron is starting a new outburst of activity which is compatible with a sporadic cometary behavior not related to heliocentric distance.

  6. Fuzzy-logic-based hybrid locomotion mode classification for an active pelvis orthosis: Preliminary results.

    PubMed

    Yuan, Kebin; Parri, Andrea; Yan, Tingfang; Wang, Long; Munih, Marko; Vitiello, Nicola; Wang, Qining

    2015-01-01

    In this paper, we present a fuzzy-logic-based hybrid locomotion mode classification method for an active pelvis orthosis. Locomotion information measured by the onboard hip joint angle sensors and the pressure insoles is used to classify five locomotion modes, including two static modes (sitting, standing still), and three dynamic modes (level-ground walking, ascending stairs, and descending stairs). The proposed method classifies these two kinds of modes first by monitoring the variation of the relative hip joint angle between the two legs within a specific period. Static states are then classified by the time-based absolute hip joint angle. As for dynamic modes, a fuzzy-logic based method is proposed for the classification. Preliminary experimental results with three able-bodied subjects achieve an off-line classification accuracy higher than 99.49%.

  7. Loss of succinate dehydrogenase activity results in dependency on pyruvate carboxylation for cellular anabolism.

    PubMed

    Lussey-Lepoutre, Charlotte; Hollinshead, Kate E R; Ludwig, Christian; Menara, Mélanie; Morin, Aurélie; Castro-Vega, Luis-Jaime; Parker, Seth J; Janin, Maxime; Martinelli, Cosimo; Ottolenghi, Chris; Metallo, Christian; Gimenez-Roqueplo, Anne-Paule; Favier, Judith; Tennant, Daniel A

    2015-11-02

    The tricarboxylic acid (TCA) cycle is a central metabolic pathway responsible for supplying reducing potential for oxidative phosphorylation and anabolic substrates for cell growth, repair and proliferation. As such it thought to be essential for cell proliferation and tissue homeostasis. However, since the initial report of an inactivating mutation in the TCA cycle enzyme complex, succinate dehydrogenase (SDH) in paraganglioma (PGL), it has become clear that some cells and tissues are not only able to survive with a truncated TCA cycle, but that they are also able of supporting proliferative phenotype observed in tumours. Here, we show that loss of SDH activity leads to changes in the metabolism of non-essential amino acids. In particular, we demonstrate that pyruvate carboxylase is essential to re-supply the depleted pool of aspartate in SDH-deficient cells. Our results demonstrate that the loss of SDH reduces the metabolic plasticity of cells, suggesting vulnerabilities that can be targeted therapeutically.

  8. Active vibration absorber for CSI evolutionary model: Design and experimental results

    NASA Technical Reports Server (NTRS)

    Bruner, Anne M.; Belvin, W. Keith; Horta, Lucas G.; Juang, Jer-Nan

    1991-01-01

    The development of control of large flexible structures technology must include practical demonstration to aid in the understanding and characterization of controlled structures in space. To support this effort, a testbed facility was developed to study practical implementation of new control technologies under realistic conditions. The design is discussed of a second order, acceleration feedback controller which acts as an active vibration absorber. This controller provides guaranteed stability margins for collocated sensor/actuator pairs in the absence of sensor/actuator dynamics and computational time delay. The primary performance objective considered is damping augmentation of the first nine structural modes. Comparison of experimental and predicted closed loop damping is presented, including test and simulation time histories for open and closed loop cases. Although the simulation and test results are not in full agreement, robustness of this design under model uncertainty is demonstrated. The basic advantage of this second order controller design is that the stability of the controller is model independent.

  9. Synthesizing Nanomaterials for Energy Applications: Probing Activity as a Function of Composition, Morphology and Purity to Address Key Issues Associated with Fuel Cells and Li-Ion Batteries

    NASA Astrophysics Data System (ADS)

    Scofield, Megan Elaine

    With the growing need to find alternative clean energy sources to fossil fuels, research into developing efficient fuel cells and batteries stands at the forefront of this grand effort. However, before mass commercialization, fundamental key issues need to be addressed. For example, fuel cells are subject to high catalyst costs and poor durability of the underlying carbon support. As a way to alleviate these issues, we have synthesized ultrathin one-dimensional (1D) alloy nanowires to probe the effect of composition, purity, and one-dimensionality upon the observed overall activity, performance, and durability. In terms of chemical composition, crystalline ultrathin PtM alloy nanowires (NWs) ('M' = Fe, Co, Ru, Cu, and Au) were generated and subsequently evaluated for the hydrogen oxidation reaction (HOR). Additionally, ternary-based catalysts were synthesized (PtRuFe) in order to analyze how chemical composition influences CO tolerance as well as methanol oxidation reaction (MOR) and formic acid oxidation reaction (FAOR) activities. In both cases, we utilized a sustainably mild, ambient wet-synthesis method for the fabrication of chemically pure and crystalline systems in order to fabricate ultrathin, homogeneous alloy NWs. Moreover, in these studies, our NW systems exhibit favorable synergistic electronic effects with respect to controls. To address another fundamental issue associated with the durability of fuel cells, we have synthesized various metal oxide and perovskite materials of different sizes and chemical compositions as supports for Pt nanoparticles (NPs). Specifically, we have demonstrated favorable metal support interactions between the Pt NPs and the SrRuO3 NP supports, which lead to increased MOR activity as compared with not only the other metal oxide supports tested but also the commercial Pt NP/C standard. In terms of Li-ion batteries, LiFePO4 materials have become increasingly popular as a cathode material due to the many benefits they possess

  10. LIM-homeodomain transcription factor Awh is a key component activating all three fibroin genes, fibH, fibL and fhx, in the silk gland of the silkworm, Bombyx mori.

    PubMed

    Kimoto, Mai; Tsubota, Takuya; Uchino, Keiro; Sezutsu, Hideki; Takiya, Shigeharu

    2015-01-01

    In the silkworm Bombyx mori, three fibroin genes, fibroin-heavy-chain (fibH), fibroin-light-chain (fibL) and fibrohexamerin (fhx), are coexpressed only in the posterior silk gland (PSG) cells, while the sericin genes encoding silk glue proteins are expressed in the middle silk gland (MSG) cells. Silk gland factor-2 (SGF-2) is a PSG-specific activator complex of fibH, composed of a LIM-homeodomain protein, Awh, and its cofactors, Ldb and Lcaf. We investigated whether SGF-2 can activate other fibroin genes using transgenic silkworms. The genes for Ldb and Lcaf were expressed ubiquitously in various tissues, while the gene for Awh was expressed strictly specific in PSG of the wild type silkworms. Misexpression of Awh in transgenic silkworms induced ectopic expression of fibL and fhx as well as fibH in MSG. Coincidently with the induction of fibL and fhx by Awh, binding of SGF-2 to the promoter of fibL and fhx was detected in vitro, and SGF-2 binds directly to the fhx core promoter. Ectopic expression of the fibroin genes was observed at high levels in the middle part of MSG. Moreover, fibL and fhx were induced in the anterior silk gland (ASG) of the transgenic silkworms, but fibH was not. These results indicate that Awh is a key activator of all three fibroin genes, and the activity is probably regulated in conjunction with additional factors.

  11. UV-induced expression of key component of the tanning process, the POMC and MC1R genes, is dependent on the p-38-activated upstream stimulating factor-1 (USF-1).

    PubMed

    Corre, Sébastien; Primot, Aline; Sviderskaya, Elena; Bennett, Dorothy C; Vaulont, Sophie; Goding, Colin R; Galibert, Marie-Dominique

    2004-12-03

    Protection against UV-mediated DNA damage and the onset of oncogenesis is afforded by the tanning response in which UV irradiation triggers melanocytes to increase production of melanin that is then transferred to keratinocytes. A key component of the tanning process is the UV-mediated induction of the pro-opiomelanocortin (POMC) and MC1R genes encoding the alpha-melanocyte-stimulating hormone and its receptor, respectively, which play a crucial role in pigmentation by regulating the intracellular levels of cAMP. How these genes are regulated in response to UV irradiation is not known. Here we have shown that UV-induced activation of the POMC and MC1R promoters is mediated by p38 stress-activated kinase signaling to the transcription factor, upstream stimulating factor-1 (USF-1). Importantly, melanocytes derived from USF-1 -/- mice exhibit a defective UV response and fail to activate POMC and MC1R expression in response to UV irradiation. The results define USF-1 as a critical UV-responsive activator of genes implicated in protection from solar radiation.

  12. Key Brainstem Structures Activated during Hypoxic Exposure in One-day-old Mice Highlight Characteristics for Modeling Breathing Network in Premature Infants

    PubMed Central

    Joubert, Fanny; Loiseau, Camille; Perrin-Terrin, Anne-Sophie; Cayetanot, Florence; Frugière, Alain; Voituron, Nicolas; Bodineau, Laurence

    2016-01-01

    We mapped and characterized changes in the activity of brainstem cell groups under hypoxia in one-day-old newborn mice, an animal model in which the central nervous system at birth is particularly immature. The classical biphasic respiratory response characterized by transient hyperventilation, followed by severe ventilation decline, was associated with increased c-FOS immunoreactivity in brainstem cell groups: the nucleus of the solitary tract, ventral reticular nucleus of the medulla, retrotrapezoid/parafacial region, parapyramidal group, raphe magnus nucleus, lateral, and medial parabrachial nucleus, and dorsal subcoeruleus nucleus. In contrast, the hypoglossal nucleus displayed decreased c-FOS immunoreactivity. There were fewer or no activated catecholaminergic cells activated in the medulla oblongata, whereas ~45% of the c-FOS-positive cells in the dorsal subcoeruleus were co-labeled. Approximately 30% of the c-FOS-positive cells in the parapyramidal group were serotoninergic, whereas only a small portion were labeled for serotonin in the raphe magnus nucleus. None of the c-FOS-positive cells in the retrotrapezoid/parafacial region were co-labeled for PHOX2B. Thus, the hypoxia-activated brainstem neuronal network of one-day-old mice is characterized by (i) the activation of catecholaminergic cells of the dorsal subcoeruleus nucleus, a structure implicated in the strong depressive pontine influence previously reported in the fetus but not in newborns, (ii) the weak activation of catecholaminergic cells of the ventral reticular nucleus of the medulla, an area involved in hypoxic hyperventilation, and (iii) the absence of PHOX2B-positive cells activated in the retrotrapezoid/parafacial region. Based on these results, one-day-old mice could highlight characteristics for modeling the breathing network of premature infants. PMID:28018238

  13. Visualizing changes in circuit activity resulting from denervation and reinnervation using immediate early gene expression.

    PubMed

    Temple, Meredith D; Worley, Paul F; Steward, Oswald

    2003-04-01

    We describe a novel strategy to evaluate circuit function after brain injury that takes advantage of experience-dependent immediate early gene (IEG) expression. When normal rats undergo training or are exposed to a novel environment, there is a strong induction of IEG expression in forebrain regions, including the hippocampus. This gene induction identifies the neurons that are engaged during the experience. Here, we demonstrate that experience-dependent IEG induction is diminished after brain injury in young adult rats (120-200 gm), specifically after unilateral lesions of the entorhinal cortex (EC), and then recovers with a time course consistent with reinnervation. In situ hybridization techniques were used to assess the expression of the activity-regulated cytoskeleton-associated protein Arc at various times after the lesion (4, 8, 12, 16, or 30 d). One group of rats was allowed to explore a complex novel environment for 1 hr; control operated animals remained in their home cage. In unoperated animals, exposure to the novel environment induced Arc mRNA levels in most pyramidal neurons in CA1, in many pyramidal neurons in CA3, and in a small number of dentate granule cells. This characteristic pattern of induction was absent at early time points after unilateral EC lesions (4 and 8 d) but recovered progressively at later time points. The recovery of Arc expression occurred with approximately the same time course as the reinnervation of the dentate gyrus as a result of postlesion sprouting. These results document a novel approach for quantitatively assessing activity-regulated gene expression in polysynaptic circuits after trauma.

  14. Metal dispersion resulting from mining activities in coastal environments: a pathways approach

    USGS Publications Warehouse

    Koski, Randolph A.

    2012-01-01

    Acid rock drainage (ARD) and disposal of tailings that result from mining activities impact coastal areas in many countries. The dispersion of metals from mine sites that are both proximal and distal to the shoreline can be examined using a pathways approach in which physical and chemical processes guide metal transport in the continuum from sources (sulfide minerals) to bioreceptors (marine biota). Large amounts of metals can be physically transported to the coastal environment by intentional or accidental release of sulfide-bearing mine tailings. Oxidation of sulfide minerals results in elevated dissolved metal concentrations in surface waters on land (producing ARD) and in pore waters of submarine tailings. Changes in pH, adsorption by insoluble secondary minerals (e.g., Fe oxyhydroxides), and precipitation of soluble salts (e.g., sulfates) affect dissolved metal fluxes. Evidence for bioaccumulation includes anomalous metal concentrations in bivalves and reef corals, and overlapping Pb isotope ratios for sulfides, shellfish, and seaweed in contaminated environments. Although bioavailability and potential toxicity are, to a large extent, functions of metal speciation, specific uptake pathways, such as adsorption from solution and ingestion of particles, also play important roles. Recent emphasis on broader ecological impacts has led to complementary methodologies involving laboratory toxicity tests and field studies of species richness and diversity.

  15. Anaerobic homolactate fermentation with Saccharomyces cerevisiae results in depletion of ATP and impaired metabolic activity.

    PubMed

    Abbott, Derek A; van den Brink, Joost; Minneboo, Inge M K; Pronk, Jack T; van Maris, Antonius J A

    2009-05-01

    Conversion of glucose to lactic acid is stoichiometrically equivalent to ethanol formation with respect to ATP formation from substrate-level phosphorylation, redox equivalents and product yield. However, anaerobic growth cannot be sustained in homolactate fermenting Saccharomyces cerevisiae. ATP-dependent export of the lactate anion and/or proton, resulting in net zero ATP formation, is suspected as the underlying cause. In an effort to understand the mechanisms behind the decreased lactic acid production rate in anaerobic homolactate cultures of S. cerevisiae, aerobic carbon-limited chemostats were performed and subjected to anaerobic perturbations in the presence of high glucose concentrations. Intracellular measurements of adenosine phosphates confirmed ATP depletion and decreased energy charge immediately upon anaerobicity. Unexpectedly, readily available sources of carbon and energy, trehalose and glycogen, were not activated in homolactate strains as they were in reference strains that produce ethanol. Finally, the anticipated increase in maximal velocity (V(max)) of glycolytic enzymes was not observed in homolactate fermentation suggesting the absence of protein synthesis that may be attributed to decreased energy availability. Essentially, anaerobic homolactate fermentation results in energy depletion, which, in turn, hinders protein synthesis, central carbon metabolism and subsequent energy generation.

  16. Characteristics of Physical Activity Programs for Older Adults: Results of a Multisite Survey

    ERIC Educational Resources Information Center

    Hughes, Susan L.; Williams, Barbara; Molina, Lourdes C.; Bayles, Constance; Bryant, Lucinda L.; Harris, Jeffrey R.; Hunter, Rebecca; Ivey, Susan; Watkins, Ken

    2005-01-01

    Purpose: Although increased participation in physical activity by older adults is a major public health goal, little is known about the supply and use of physical activity programs in the United States. Design and Methods: Seven academic centers in diverse geographic areas surveyed physical activity programs for older adults. Five sites conducted…

  17. Physical Education and Physical Activity: Results from the School Health Policies and Programs Study 2006

    ERIC Educational Resources Information Center

    Lee, Sarah M.; Burgeson, Charlene R.; Fulton, Janet E.; Spain, Christine G.

    2007-01-01

    Background: Comprehensive school-based physical activity programs consist of physical education and other physical activity opportunities including recess and other physical activity breaks, intramurals, interscholastic sports, and walk and bike to school initiatives. This article describes the characteristics of school physical education and…

  18. 78 FR 26748 - Certain Activated Carbon From the People's Republic of China: Preliminary Results of Antidumping...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-05-08

    ... International Trade Administration Certain Activated Carbon From the People's Republic of China: Preliminary... duty order on certain activated carbon from the People's Republic of China (``PRC'') for the period of... The merchandise subject to the order is certain activated carbon.\\1\\ The products are...

  19. Preliminary Results from the iMUSH Active Source Seismic Experiment

    NASA Astrophysics Data System (ADS)

    Levander, Alan; Kiser, Eric; Palomeras, Imma; Zelt, Colin; Schmandt, Brandon; Hansen, Steve; Harder, Steven; Creagar, Kenneth; Vidale, John; Abers, Geoffrey

    2015-04-01

    iMUSH (imaging Magma Under Saint Helens) is a US NSF sponsored multi-disciplinary investigation of Mount Saint Helens (MSH), currently the most active volcano in the Cascades arc in the northwestern United States. The project consists of active and passive seismic experiments, extensive magnetotelluric sounding, and geological/geochemical studies involving scientists at 7 institutions in the U.S. and Europe. The long-term goal of the seismic project is to combine analysis of the active source data with that of data from the 70 element broadband seismograph operating from summer 2014 until 2016. Combining seismic and MT analyses with other data, we hope to image the MSH volcanic plumbing system from the surface to the subducting Juan de Fuca slab. Here we describe preliminary results of the iMUSH active source seismic experiment, conducted in July and August 2014. The active source experiment consisted of twenty-three 454 or 908 kg weight shots recorded by ~3500 seismographs deployed at ~6,000 locations. Of these instruments, ~900 Nodal Seismic instruments were deployed continuously for two weeks in an areal array within 10 km of the MSH summit. 2,500 PASSCAL Texan instruments were deployed twice for five days in 3 areal arrays and 2 dense orthogonal linear arrays that extended from MSH to distances > 80 km. Overall the data quality from the shots is excellent. The seismograph arrays also recorded dozens of micro-earthquakes beneath the MSH summit and along the MSH seismic zone, and numerous other local and regional earthquakes. In addition, at least one low frequency event beneath MSH was recorded during the experiment. At this point we have begun various types of analysis of the data set: We have determined an average 1D Vp structure from stacking short-term/long-term average ratios, we have determined the 2-D Vp structure from ray-trace inversions along the two orthogonal profiles (in the NW-SE and NE-SW directions), and we have made low-fold CMP stacks of the

  20. Soil hydrological and soil property changes resulting from termite activity on agricultural fields in Burkina Faso

    NASA Astrophysics Data System (ADS)

    Mettrop, I.; Cammeraat, L. H.; Verbeeten, E.

    2009-04-01

    Termites are important ecosystem-engineers in subtropical and tropical regions. The effect of termite activity affecting soil infiltration is well documented in the Sahelian region. Most studies find increased infiltration rates on surfaces that are affected by termite activity in comparison to crusted areas showing non-termite presence. Crusted agricultural fields in the Sanmatenga region in Burkina Faso with clear termite activity were compared to control fields without visual ground dwelling termite activity. Fine scale rainfall simulations were carried out on crusted termite affected and control sites. Furthermore soil moisture change, bulk density, soil organic matter as well as general soil characteristics were studied. The top soils in the study area were strongly crusted (structural crust) after the summer rainfall and harvest of millet. They have a loamy sand texture underlain by a shallow sandy loam Bt horizon. The initial soil moisture conditions were significantly higher on the termite plots when compared to control sites. It was found that the amount of runoff produced on the termite plots was significantly higher, and also the volumetric soil moisture content after the experiments was significantly lower if compared to the control plots. Bulk density showed no difference whereas soil organic matter was significantly higher under termite affected areas, in comparison to the control plots. Lab tests showed no significant difference in hydrophobic behavior of the topsoil and crust material. Micro and macro-structural properties of the topsoil did not differ significantly between the termite sites and the control sites. The texture of the top 5 cm of the soil was also found to be not significantly different. The infiltration results are contradictory to the general literature, which reports increased infiltration rates after prolonged termite activity although mostly under different initial conditions. The number of nest entrances was clearly higher in

  1. The constitutive active/androstane receptor facilitates unique phenobarbital-induced expression changes of genes involved in key pathways in precancerous liver and liver tumors.

    PubMed

    Phillips, Jennifer M; Burgoon, Lyle D; Goodman, Jay I

    2009-08-01

    Our overall goal is to elucidate progressive changes, in expression and methylation status, of genes which play key roles in phenobarbital (PB)-induced liver tumorigenesis, with an emphasis on their potential to affect signaling through critical pathways involved in the regulation of cell growth and differentiation. PB-elicited unique expression changes of genes, including some of those identified previously as exhibiting regions of altered DNA methylation, were discerned in precancerous liver tissue and/or individual liver tumors from susceptible constitutive active/androstane receptor (CAR) wild-type (WT) compared with resistant CAR knockout (KO) mice. Many of these function in crucial cancer-related processes, for example, angiogenesis, apoptosis, cell cycle, DNA methylation, Hedgehog signaling, invasion/metastasis, Notch signaling, and Wnt signaling. Furthermore, a subset of the uniquely altered genes contained CAR response elements (CAREs). This included Gadd45b, a coactivator of CAR and inhibitor of apoptosis, and two DNA methyltransferases (Dnmt1, Dnmt3a). The presence of CAREs in Dnmts suggests a potential direct link between PB and altered DNA methylation. The current data are juxtaposed with the effects of PB on DNA methylation and gene expression which occurred uniquely in liver tumor-prone B6C3F1 mice, as compared with the resistant C57BL/6, following 2 or 4 weeks of treatment. Collectively, these data reveal a comprehensive view of PB-elicited molecular alterations (i.e., changes in gene expression and DNA methylation) that can facilitate hepatocarcinogenesis. Notably, candidate genes for initial "fingerprints" of early and late stages of PB-induced tumorigenesis are proposed.

  2. The Constitutive Active/Androstane Receptor Facilitates Unique Phenobarbital-Induced Expression Changes of Genes Involved in Key Pathways in Precancerous Liver and Liver Tumors

    PubMed Central

    Phillips, Jennifer M.; Burgoon, Lyle D.; Goodman, Jay I.

    2009-01-01

    Our overall goal is to elucidate progressive changes, in expression and methylation status, of genes which play key roles in phenobarbital (PB)–induced liver tumorigenesis, with an emphasis on their potential to affect signaling through critical pathways involved in the regulation of cell growth and differentiation. PB-elicited unique expression changes of genes, including some of those identified previously as exhibiting regions of altered DNA methylation, were discerned in precancerous liver tissue and/or individual liver tumors from susceptible constitutive active/androstane receptor (CAR) wild-type (WT) compared with resistant CAR knockout (KO) mice. Many of these function in crucial cancer-related processes, for example, angiogenesis, apoptosis, cell cycle, DNA methylation, Hedgehog signaling, invasion/metastasis, Notch signaling, and Wnt signaling. Furthermore, a subset of the uniquely altered genes contained CAR response elements (CAREs). This included Gadd45b, a coactivator of CAR and inhibitor of apoptosis, and two DNA methyltransferases (Dnmt1, Dnmt3a). The presence of CAREs in Dnmts suggests a potential direct link between PB and altered DNA methylation. The current data are juxtaposed with the effects of PB on DNA methylation and gene expression which occurred uniquely in liver tumor-prone B6C3F1 mice, as compared with the resistant C57BL/6, following 2 or 4 weeks of treatment. Collectively, these data reveal a comprehensive view of PB-elicited molecular alterations (i.e., changes in gene expression and DNA methylation) that can facilitate hepatocarcinogenesis. Notably, candidate genes for initial “fingerprints” of early and late stages of PB-induced tumorigenesis are proposed. PMID:19482888

  3. Addition of prothrombin to plasma can result in a paradoxical increase in activated partial thromboplastin time.

    PubMed

    Hansson, Kenny M; Björkqvist, Jenny; Deinum, Johanna

    2014-12-01

    In the activated partial thromboplastin time (APTT) assay, a variety of nonphysiological reagents is used to induce contact activation. The sensitivity of the APTT response for different thrombin inhibitors has previously been found to be dependent on the used reagent. Recently, infusion of prothrombin (FII) has been used in in-vivo coagulopathy models and its effect has been analyzed in different assays. Therefore, we investigated whether the FII plasma concentration might affect APTT using different commercial reagents, applying both turbidimetry and viscometry. We compared both plasma-derived human FII (pd-hFII) and recombinant human FII (r-hFII). Similar results were found for pd-hFII and r-hFII with different APTT reagents. As expected, no effect on APTT was found by increasing the plasma concentration of FII using APTT reagents consisting of ellagic acid (Actin FS or Actin). Although with Pathromtin SL, consisting of SiO2, only a slight increase was found, with most other commercial APTT reagents, consisting of SiO2 or kaolin, APTT dose-dependently increased by increasing concentration of FII. Therefore, both Pathromtin SL and Actin FS were used to compare r-hFII and pd-hFII by determining the KM at 37C using FII-depleted plasma, providing values of 6 ± 0.3 nmol/l FII for both. Thus, at normal plasma concentrations of FII, the maximal initial thrombin generation rate should be reached and no effect on the coagulation time is expected at higher FII concentrations. To completely avoid the paradoxical effect in the APTT assay at FII concentrations higher than normal, Actin or Actin FS is the preferable reagent.

  4. Repeated Activation of a CS-US-Contingency Memory Results in Sustained Conditioned Responding

    PubMed Central

    Joos, Els; Vansteenwegen, Debora; Vervliet, Bram; Hermans, Dirk

    2013-01-01

    Individuals seem to differ in conditionability, i.e., the ease by which the contingent presentation of two stimuli will lead to a conditioned response. In contemporary learning theory, individual differences in the etiology and maintenance of anxiety disorders are, among others, explained by individual differences in temperamental variables (Mineka and Zinbarg, 2006). One such individual difference variable is how people process a learning experience when the conditioning stimuli are no longer present. Repeatedly thinking about the conditioning experience, as in worry or rumination, might prolong the initial (fear) reactions and as such, might leave certain individuals more vulnerable to developing an anxiety disorder. However, in human conditioning research, relatively little attention has been devoted to the processing of a memory trace after its initial acquisition, despite its potential influences on subsequent performance. Post-acquisition processing can be induced by mental reiteration of a conditioned stimulus-unconditioned stimulus (CS-US)-contingency. Using a human conditioned suppression paradigm, we investigated the effect of repeated activations of a CS-US-contingency memory on the level of conditioned responding at a later test. Results of three experiments showed more sustained responding to a “rehearsed” CS+ as compared to a “non-rehearsed” CS+. Moreover, the second experiment showed no effect of rehearsal when only the CS was rehearsed instead of the CS-US-contingency. The third experiment demonstrated that mental CS-US-rehearsal has the same effect regardless of whether it was cued by the CS and a verbal reference to the US or by a neutral signal, making the rehearsal “purely mental.” In sum, it was demonstrated that post-acquisition activation of a CS-US-contingency memory can impact conditioned responding, underlining the importance of post-acquisition processes in conditioning. This might indicate that individuals who are more prone

  5. Repeated Activation of a CS-US-Contingency Memory Results in Sustained Conditioned Responding.

    PubMed

    Joos, Els; Vansteenwegen, Debora; Vervliet, Bram; Hermans, Dirk

    2013-01-01

    Individuals seem to differ in conditionability, i.e., the ease by which the contingent presentation of two stimuli will lead to a conditioned response. In contemporary learning theory, individual differences in the etiology and maintenance of anxiety disorders are, among others, explained by individual differences in temperamental variables (Mineka and Zinbarg, 2006). One such individual difference variable is how people process a learning experience when the conditioning stimuli are no longer present. Repeatedly thinking about the conditioning experience, as in worry or rumination, might prolong the initial (fear) reactions and as such, might leave certain individuals more vulnerable to developing an anxiety disorder. However, in human conditioning research, relatively little attention has been devoted to the processing of a memory trace after its initial acquisition, despite its potential influences on subsequent performance. Post-acquisition processing can be induced by mental reiteration of a conditioned stimulus-unconditioned stimulus (CS-US)-contingency. Using a human conditioned suppression paradigm, we investigated the effect of repeated activations of a CS-US-contingency memory on the level of conditioned responding at a later test. Results of three experiments showed more sustained responding to a "rehearsed" CS+ as compared to a "non-rehearsed" CS+. Moreover, the second experiment showed no effect of rehearsal when only the CS was rehearsed instead of the CS-US-contingency. The third experiment demonstrated that mental CS-US-rehearsal has the same effect regardless of whether it was cued by the CS and a verbal reference to the US or by a neutral signal, making the rehearsal "purely mental." In sum, it was demonstrated that post-acquisition activation of a CS-US-contingency memory can impact conditioned responding, underlining the importance of post-acquisition processes in conditioning. This might indicate that individuals who are more prone to mentally

  6. Upper Pleistocene - Holocene activity of the Carrascoy Fault (Murcia, SE Spain): preliminary results from paleoseismological research.

    NASA Astrophysics Data System (ADS)

    Martin-Banda, Raquel; Garcia-Mayordomo, Julian; Insua-Arevalo, Juan M.; Salazar, Angel; Rodriguez-Escudero, Emilio; Alvarez-Gomez, Jose A.; Martinez-Diaz, Jose J.; Herrero, Maria J.; Medialdea, Alicia

    2014-05-01

    The Carrascoy Fault is located in the Internal Zones of the Betic Cordillera (Southern Spain). In particular, the Carrascoy Fault is one of the major faults forming the Eastern Betic Shear Zone, the main structure accommodating the convergence between Nubian and Eurasian plates in the westernmost Mediterranean. So far, the Carrascoy Fault has been defined as a left-lateral strike-slip fault. It extends for at least 31 km in a NE-SW trend from the village of Zeneta (Murcia) at its northeastern tip, to the Cañaricos village, controlling the northern edge of the Carrascoy Range and its linkage to the Guadalentin Depression towards the southwest. This is an area of moderate seismic activity, but densely populated, the capital of the region, Murcia, being settled very close to the fault. Hence, the knowledge of the structure and kinematics of the Carrascoy Fault is essential for assessing reliably the seismic hazard of the region. We present a detailed-scale geological and geomorphological map along the fault zone created from a LIDAR DEM combined with fieldwork, and geological and geophysical information. Furthermore, a number of trenches have been dug across the fault at different locations providing insights in the fault most recent activity as well as paleoseismic data. Preliminary results suggest that the Cararscoy Fault has recently changed its kinematic showing a near pure reverse motion. According to this, the fault can be divided into two distinct segments, the eastern one: Zeneta - Fuensanta, and the western one: Fuensanta - Cañaricos, each one having its own characteristic style and geodynamics. Some new active strands of the fault locate at the foot of the very first relief towards the North of the older strand, forming the current southern border of the Guadalentin Depression. These new faults show an increasingly reverse component westwards, so that the Fuensanta - Cañaricos segment is constituted by thrusts, which are blind at its western end

  7. Understanding dog owners' increased levels of physical activity: results from RESIDE.

    PubMed

    Cutt, Hayley; Giles-Corti, Billie; Knuiman, Matthew; Timperio, Anna; Bull, Fiona

    2008-01-01

    We examined the influence of dog ownership on physical activity, independent of demographic, intrapersonal, and perceived environmental factors, in a cross-sectional survey of 1813 adults. Although only 23% of the dog owners walked their dogs 5 or more times per week, the adjusted odds of achieving sufficient physical activity and walking were 57% to 77% higher among dog owners compared with those not owning dogs (P< .05). Dog ownership was independently associated with physical activity and walking. Actively encouraging more dog walking may increase community physical activity levels.

  8. Can leisure-time physical activity improve health checkup results? Evidence from Japanese occupational panel data

    PubMed Central

    Oshio, Takashi; Tsutsumi, Akizumi; Inoue, Akiomi

    2016-01-01

    Objectives: We examined the extent to which changes in worker health, as measured by health checkup items, were associated with increased intensity of leisure-time physical activity (LTPA) after controlling for individual time-invariant attributes. Methods: We used panel data from two to four waves of a Japanese occupational cohort survey, focusing on 30,206 observations of 10,106 individuals (7,669 men and 2,437 women) aged 18-76 years. We estimated first-difference and mean-centered fixed effects models to examine how changes in 10 health checkup items were associated with changes in LTPA intensity. We considered four LTPA intensity levels (none, low, moderate, and vigorous), based on self-reported assessments. Results: For men, low-density lipoprotein cholesterol levels, glycated hemoglobin levels, body mass index, and waist circumference improved when LTPA intensity was increased even at a low level, whereas triglyceride, high-density lipoprotein cholesterol, and fasting blood glucose levels improved when LTPA intensity was increased to moderate or vigorous levels. Blood pressure (both systolic and diastolic) and total cholesterol levels were only modestly responsive to changes in LTPA intensity. For women, blood pressure (both systolic and diastolic) and waist circumference were negatively associated with LTPA intensity, whereas the other variables showed more modest effects. Conclusions: The results suggest that even low- to moderate-intensity LTPA can improve health checkup results; however, the lowest LTPA intensity associated with improvement in health depends on health-risk factors as well as gender. PMID:27265532

  9. Physical activity in solid organ transplant recipients: organizational aspects and preliminary results of the Italian project.

    PubMed

    Roi, G S; Stefoni, S; Mosconi, G; Brugin, E; Burra, P; Ermolao, A; Granito, M; Macini, P; Mastrosimone, S; Nacchia, F; Pegoraro, C; Rigotti, P; Sella, G; Sgarzi, S; Tamè, M R; Totti, V; Trerotola, M; Tripi, F; Nanni Costa, A

    2014-09-01

    Most of the difficulties when trying to realize the proposal to prescribe physical activity for transplantation patients come from patient attitudes and cultural beliefs that ignore the benefits of exercise, but there also are organizational aspects arising from the difficulties that these patients face in accessing supervised exercise facilities. To address these difficulties, the Italian study project "Transplant … and Now Sport" was developed based on a model of cooperation among transplantation specialists, sports physicians, and exercise specialists organized as a team combining their specific skills to effectively actuate the physical exercise programs. This preliminary report is based on 26 patients (16 male, 10 female; 47.8±10.0 years old; 21 kidney and 5 liver transplantations; time from transplantation 2.3±1.4 years) who performed prescribed and supervised exercises consisting of 3 sessions per week of aerobic and strengthening exercises for 1 year. Preliminary results show a significant decrease in body mass index (t=1.966; P<.05) and a significant increase in peak aerobic power (t=4.535; P<.01) and maximum workload (t=4.665; P<.01) on the incremental cycling test. Also maximum strength of knee extensors (t=2.933; P<.05) and elbow flexors (t=2.450; P<.05) and countermovement jump performance (t=2.303; P<.05) significantly increased. Creatinine and proteinuria tended to decrease, but the differences were not significant. In health-related quality of life assessed by the SF-36 questionnaire, the Bodily Pain, General Health, Vitality, Social Functioning, and Role Emotional scale scores showed a significant improvement (P<.05). Preliminary results of the study protocol "Transplant…and Now Sport" show the positive effects of the model based on cooperation among transplantation centers, sports medicine centers, and gyms in the administration of a supervised exercise prescription. These data should be considered a contribution to developing and promoting

  10. The P 2 ' residue is a key determinant of mesotrypsin specificity: Engineering a high-affinity inhibitor with anticancer activity

    SciTech Connect

    Salameh, Moh'd A.; Soares, Alexei S.; Hockla, Alexandra; Radisky, Derek C.; Radisky, Evette S.

    2011-11-15

    PRSS3/mesotrypsin is an atypical isoform of trypsin, the up-regulation of which has been implicated in promoting tumour progression. Mesotrypsin inhibitors could potentially provide valuable research tools and novel therapeutics, but small-molecule trypsin inhibitors have low affinity and little selectivity, whereas protein trypsin inhibitors bind poorly and are rapidly degraded by mesotrypsin. In the present study, we use mutagenesis of a mesotrypsin substrate, APPI (amyloid precursor protein Kunitz protease inhibitor domain), and of a poor mesotrypsin inhibitor, BPTI (bovine pancreatic trypsin inhibitor), to dissect mesotrypsin specificity at the key P2' position. We find that bulky and charged residues strongly disfavour binding, whereas acidic residues facilitate catalysis. Crystal structures of mesotrypsin complexes with BPTI variants provide structural insights into mesotrypsin specificity and inhibition. Through optimization of the P1 and P2' residues of BPTI, we generate a stable high-affinity mesotrypsin inhibitor with an equilibrium binding constant Ki of 5.9 nM, a >2000-fold improvement in affinity over native BPTI. Using this engineered inhibitor, we demonstrate the efficacy of pharmacological inhibition of mesotrypsin in assays of breast cancer cell malignant growth and pancreatic cancer cell invasion. Although further improvements in inhibitor selectivity will be important before clinical potential can be realized, the results of the present study support the feasibility of engineering protein protease inhibitors of mesotrypsin and highlight their therapeutic potential.

  11. The P2’ residue is a key determinant of mesotrypsin specificity: Engineering a high-affinity inhibitor with anticancer activity

    SciTech Connect

    Salameh, M.A.; Soares, A.; Hockla, A.; Radisky, D. C.; Radisky, E. S.

    2011-11-15

    PRSS3/mesotrypsin is an atypical isoform of trypsin, the up-regulation of which has been implicated in promoting tumor progression. Mesotrypsin inhibitors could potentially provide valuable research tools and novel therapeutics, but small-molecule trypsin inhibitors have low affinity and little selectivity, whereas protein trypsin inhibitors bind poorly and are rapidly degraded by mesotrypsin. In the present study, we use mutagenesis of a mesotrypsin substrate, APPI (amyloid precursor protein Kunitz protease inhibitor domain), and of a poor mesotrypsin inhibitor, BPTI (bovine pancreatic trypsin inhibitor), to dissect mesotrypsin specificity at the key P'{sub 2} position. We find that bulky and charged residues strongly disfavor binding, whereas acidic residues facilitate catalysis. Crystal structures of mesotrypsin complexes with BPTI variants provide structural insights into mesotrypsin specificity and inhibition. Through optimization of the P{sub 1} and P'{sub 2} residues of BPTI, we generate a stable high-affinity mesotrypsin inhibitor with an equilibrium binding constant K{sub i} of 5.9 nM, a >2000-fold improvement in affinity over native BPTI. Using this engineered inhibitor, we demonstrate the efficacy of pharmacological inhibition of mesotrypsin in assays of breast cancer cell malignant growth and pancreatic cancer cell invasion. Although further improvements in inhibitor selectivity will be important before clinical potential can be realized, the results of the present study support the feasibility of engineering protein protease inhibitors of mesotrypsin and highlight their therapeutic potential.

  12. Right ventromedial prefrontal lesions result in paradoxical cardiovascular activation with emotional stimuli.

    PubMed

    Hilz, Max J; Devinsky, Orrin; Szczepanska, Hanna; Borod, Joan C; Marthol, Harald; Tutaj, Marcin

    2006-12-01

    Ventromedial prefrontal cortex (VMPFC) lesions can alter emotional and autonomic responses. In animals, VMPFC activation results in cardiovascular sympathetic inhibition. In humans, VMPFC modulates emotional processing and autonomic response to arousal (e.g. accompanying decision-making). The specific role of the left or right VMPFC in mediating somatic responses to non-arousing, daily-life pleasant or unpleasant stimuli is unclear. To further evaluate VMPFC interaction with autonomic processing of non-stressful emotional stimuli and assess the effects of stimulus valence, we studied patients with unilateral VMPFC lesions and assessed autonomic modulation at rest and during physical challenge, and heart rate (HR) and blood pressure (BP) responses to non-stressful neutral, pleasant and unpleasant visual stimulation (VES) via emotionally laden slides. In 6 patients (54.0 +/- 7.2 years) with left-sided VMPFC lesions (VMPFC-L), 7 patients (43.3 +/- 11.6 years) with right-sided VMPFC lesions (VMPFC-R) and 13 healthy volunteers (44.7 +/- 11.6 years), we monitored HR as R-R interval (RRI), BP, respiration, end-tidal carbon dioxide levels, and oxygen saturation at rest, during autonomic challenge by metronomic breathing, a Valsalva manoeuvre and active standing, and in response to non-stressful pleasant, unpleasant and neutral VES. Pleasantness versus unpleasantness of slides was rated on a 7-point Likert scale. At rest, during physical autonomic challenge, and during neutral VES, parameters did not differ between the patient groups and volunteers. During VES, Likert scores also were similar across the three groups. During pleasant and unpleasant VES, HR decreased (i.e. RRI increased) significantly whereas BP remained unchanged in volunteers. In VMPFC-L patients, HR decrease was insignificant with pleasant and unpleasant VES. BP slightly increased (P = 0.06) with pleasant VES but was stable with unpleasant VES. In contrast, VMPFC-R patients had significant increases in HR

  13. Plasminogen Activator Inhibitor-1 in depression: Results from Animal and Clinical Studies

    PubMed Central

    Jiang, Haitang; Li, Xiaoli; Chen, Suzhen; Lu, Na; Yue, Yingying; Liang, Jinfeng; Zhang, Zhijun; Yuan, Yonggui

    2016-01-01

    Evidence suggests that plasminogen activator inhibitor-1 (PAI-1) is a stress-related factor, and serum PAI-1 levels are increased in patients with major depressive disorders (MDD). Herein, we analysed PAI-1 protein levels in the brain, cerebrospinal fluid (CSF) and serum of rodents exposed to chronic unpredictable mild stress or treated with escitalopram. In addition, we examined PAI-1 concentrations in serum obtained from 17 drug-free depressed patients before and after escitalopram treatment. We found that PAI-1 expression was increased in area 1 of the cingulate cortex and prelimbic cortex of the medial prefrontal cortex as well as in the hippocampal cornu ammonis 3 and dentate gyrus in stressed rats. A downregulation of PAI-1 following chronic escitalopram treatment was also found. PAI-1 levels were higher in the CSF and serum in stressed rats than in controls, although the difference did not reach statistical significance in the serum. Escitalopram treatment significantly decreased PAI-1 levels in the serum, but not in the CSF. MDD patients had significantly greater serum PAI-1 concentrations than controls. Our results suggest that PAI-1 is implicated in the pathophysiology of depression. PMID:27456456

  14. The global unified parallel file system (GUPFS) project: FY 2002 activities and results

    SciTech Connect

    Butler, Gregory F.; Lee, Rei Chi; Welcome, Michael L.

    2003-04-07

    The Global Unified Parallel File System (GUPFS) project is a multiple-phase, five-year project at the National Energy Research Scientific Computing (NERSC) Center to provide a scalable, high performance, high bandwidth, shared file system for all the NERSC production computing and support systems. The primary purpose of the GUPFS project is to make it easier to conduct advanced scientific research using the NERSC systems. This is to be accomplished through the use of a shared file system providing a unified file namespace, operating on consolidated shared storage that is directly accessed by all the NERSC production computing and support systems. During its first year, FY 2002, the GUPFS project focused on identifying, testing, and evaluating existing and emerging shared/cluster file system, SAN fabric, and storage technologies; identifying NERSC user input/output (I/O) requirements, methods, and mechanisms; and developing appropriate benchmarking methodologies and benchmark codes for a parallel environment. This report presents the activities and progress of the GUPFS project during its first year, the results of the evaluations conducted, and plans for near-term and longer-term investigations.

  15. Defective Phagocytic Corpse Processing Results in Neurodegeneration and Can Be Rescued by TORC1 Activation

    PubMed Central

    Etchegaray, Jon Iker; Elguero, Emma J.; Tran, Jennifer A.; Sinatra, Vincent; Feany, Mel B.

    2016-01-01

    The removal of apoptotic cell corpses is important for maintaining homeostasis. Previously, defects in apoptotic cell clearance have been linked to neurodegeneration. However, the mechanisms underlying this are still poorly understood. In this study, we report that the absence of the phagocytic receptor Draper in glia leads to a pronounced accumulation of apoptotic neurons in the brain of Drosophila melanogaster. These dead cells persist in the brain throughout the lifespan of the organism and are associated with age-dependent neurodegeneration. Our data indicate that corpses persist because of defective phagosome maturation, rather than recognition defects. TORC1 activation, or inhibition of Atg1, in glia is sufficient to rescue corpse accumulation as well as neurodegeneration. These results suggest that phagocytosis of apoptotic neurons by glia during development is essential for brain homeostasis in adult flies. Furthermore, it suggests that TORC1 regulates Draper-mediated phagosome maturation. SIGNIFICANCE STATEMENT Previously, defects in dead cell clearance were linked to neurodegeneration, but the exact mechanisms are not well understood. In this study, we report that the absence of an engulfment receptor leads to a pronounced accumulation of dead neurons in the brain of the fruit fly Drosophila melanogaster. These dead cells persist in the brain throughout the lifespan of the organism and are associated with age-dependent neurodegeneration. Our data indicate that corpses persist because of defective degradation of cells rather than recognition of dead cells. PMID:26985028

  16. Granular Activated Carbon Treatment May Result in Higher Predicted Genotoxicity in the Presence of Bromide.

    PubMed

    Krasner, Stuart W; Lee, Tiffany Chih Fen; Westerhoff, Paul; Fischer, Natalia; Hanigan, David; Karanfil, Tanju; Beita-Sandí, Wilson; Taylor-Edmonds, Liz; Andrews, Robert C

    2016-09-06

    Certain unregulated disinfection byproducts (DBPs) are more of a health concern than regulated DBPs. Brominated species are typically more cytotoxic and genotoxic than their chlorinated analogs. The impact of granular activated carbon (GAC) on controlling the formation of regulated and selected unregulated DBPs following chlorine disinfection was evaluated. The predicted cyto- and genotoxicity of DBPs was calculated using published potencies based on the comet assay for Chinese hamster ovary cells (assesses the level of DNA strand breaks). Additionally, genotoxicity was measured using the SOS-Chromotest (detects DNA-damaging agents). The class sum concentrations of trihalomethanes, haloacetic acids, and unregulated DBPs, and the SOS genotoxicity followed the breakthrough of dissolved organic carbon (DOC), however the formation of brominated species did not. The bromide/DOC ratio was higher than the influent through much of the breakthrough curve (GAC does not remove bromide), which resulted in elevated brominated DBP concentrations in the effluent. Based on the potency of the haloacetonitriles and halonitromethanes, these nitrogen-containing DBPs were the driving agents of the predicted genotoxicity. GAC treatment of drinking or reclaimed waters with appreciable levels of bromide and dissolved organic nitrogen may not control the formation of unregulated DBPs with higher genotoxicity potencies.

  17. Active shield technology for space craft protection revisited in new laboratory results and analysis

    NASA Astrophysics Data System (ADS)

    Bamford, R.; Gibson, K. J.; Thornton, A. T.; Bradford, J.; Bingham, R.; Gargate, L.; Silva, L. O.; Fonseca, R. A.; Hapgood, M.; Norberg, C.; Todd, T.; Stamper, R.

    2009-04-01

    Energetic ions in the solar wind plasma are a known hazard to both spacecraft electronics and to astronaut's health. Of primary concern is the exposure to keV--MeV protons on manned space flights to the Moon and Mars that extend over long periods of time. Attempts to protect the spacecraft include active shields that are reminiscent of Star Trek "deflector" shields. Here we describe a new experiment to test the shielding concept of a dipole-like magnetic field and plasma, surrounding the spacecraft forming a "mini magnetosphere". Initial laboratory experiments have been conducted to determine the effectiveness of a magnetized plasma barrier to be able to expel an impacting, low beta, supersonic flowing energetic plasma representing the Solar Wind. Optical and Langmuir probe data of the plasma density, the plasma flow velocity, and the intensity of the dipole field clearly show the creation of a narrow transport barrier region and diamagnetic cavity virtually devoid of energetic plasma particles. This demonstrates the potential viability of being able to create a small "hole" in a Solar Wind plasma, of the order of the ion Larmor orbit width, in which an inhabited spacecraft could reside in relative safety. The experimental results have been quantitatively compared to a 3D particle-in-cell ‘hybrid' code simulation that uses kinetic ions and fluid electrons, showing good qualitative agreement and excellent quantitative agreement. Together the results demonstrate the pivotal role of particle kinetics in determining generic plasma transport barriers. [1] [1] R Bamford et al., "The interaction of a flowing plasma with a dipole magnetic field: measurements and modelling of a diamagnetic cavity relevant to spacecraft protection." 2008 Plasma Phys. Control. Fusion 50 124025 (11pp) doi: 10.1088/0741-3335/50/12/124025

  18. Activation of platelet-activating factor receptor in SZ95 sebocytes results in inflammatory cytokine and prostaglandin E2 production.

    PubMed

    Zhang, Qiwei; Seltmann, Holger; Zouboulis, Christos C; Travers, Jeffrey B

    2006-10-01

    Platelet-activating factor (PAF) is a group of phosphocholines with various biological effects mediated by the PAF receptor (PAF-R). Activation of the epidermal PAF-R induces the expression of inflammatory mediators, including cyclooxygenase-2 (COX-2) and prostaglandin E(2) (PGE(2)). The upregulation of COX-2 expression has been shown to be involved in sebocyte proliferation, sebaceous gland inflammation and carcinogenesis. The present study was designed to investigate whether PAF-R activation could induce the expression of COX-2 and production of PGE(2), as well as secretion of the inflammatory cytokine, interleukin-8 (IL-8), in the immortalized sebaceous gland cell line SZ95. Using calcium mobilization studies, we first confirmed that PAF can signal through PAF-R in SZ95 sebocytes. We then found that the production of IL-8 was induced following treatment with PAF-R agonist, however blocked by a specific PAF-R antagonist. Induction of COX-2 expression and increased PGE(2) production were observed in SZ95 sebocytes after PAF-R activation. Finally, it was demonstrated that the production of PGE(2), induced by PAF-R activation and mediated by COX-2 expression, was blocked following PAF-R antagonism in SZ95 sebocytes. These studies suggest that SZ95 sebocytes express functional PAF-Rs and PAF-Rs are involved in regulating the expression of inflammatory mediators, including COX-2, PGE(2) and IL-8.

  19. Mechanism of Flavoprotein l-6-Hydroxynicotine Oxidase: pH and Solvent Isotope Effects and Identification of Key Active Site Residues.

    PubMed

    Fitzpatrick, Paul F; Chadegani, Fatemeh; Zhang, Shengnan; Dougherty, Vi

    2017-02-14

    The flavoenzyme l-6-hydroxynicotine oxidase is a member of the monoamine oxidase family that catalyzes the oxidation of (S)-6-hydroxynicotine to 6-hydroxypseudooxynicotine during microbial catabolism of nicotine. While the enzyme has long been understood to catalyze oxidation of the carbon-carbon bond, it has recently been shown to catalyze oxidation of a carbon-nitrogen bond [Fitzpatrick, P. F., et al. (2016) Biochemistry 55, 697-703]. The effects of pH and mutagenesis of active site residues have now been utilized to study the mechanism and roles of active site residues. Asn166 and Tyr311 bind the substrate, while Lys287 forms a water-mediated hydrogen bond with flavin N5. The N166A and Y311F mutations result in ∼30- and ∼4-fold decreases in kcat/Km and kred for (S)-6-hydroxynicotine, respectively, with larger effects on the kcat/Km value for (S)-6-hydroxynornicotine. The K287M mutation results in ∼10-fold decreases in these parameters and a 6000-fold decrease in the kcat/Km value for oxygen. The shapes of the pH profiles are not altered by the N166A and Y311F mutations. There is no solvent isotope effect on the kcat/Km value for amines. The results are consistent with a model in which both the charged and neutral forms of the amine can bind, with the former rapidly losing a proton to a hydrogen bond network of water and amino acids in the active site prior to the transfer of hydride to the flavin.

  20. Do Sedentary Older Adults Benefit from Community-Based Exercise? Results from the Active Start Program

    ERIC Educational Resources Information Center

    Yan, Tingjian; Wilber, Kathleen H.; Aguirre, Rosa; Trejo, Laura

    2009-01-01

    Purpose: This study assessed the effectiveness of Active Start, a community-based behavior change and fitness program, designed to promote physical activity among sedentary community-dwelling older adults. Design and Methods: A quasi-experimental design was used. Data were analyzed using a within-group pretest-post-test design to calculate changes…