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. 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.

  4. 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. PMID:26177618

  5. 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

  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. Lessons and key results from 30 years of imaging spectroscopy

    NASA Astrophysics Data System (ADS)

    Green, Robert O.

    2014-09-01

    Spectroscopy was first used in 1814 by Joseph von Fraunhofer as a scientific method for discovery, and to develop and test scientific hypotheses. From this beginning, spectroscopy evolved to a broadly used analytical tool for both science and applications. In the 1970's, technology began to enable a class of instruments that measure spectra for every point in an image. The first airborne imaging spectrometer developed at the Jet Propulsion Laboratory flew in 1982. Subsequently, a wide range of imaging spectrometers have been developed, many at the Jet Propulsion Laboratory, for airborne and space platforms and they have participated in NASA mission throughout the solar system. A key lesson over this time period has been the broad applicability of imaging spectrometers to pursue a range of science and application objectives wherever there is relevant signal in the spectral range from the ultra violet to the thermal infrared. As with all optical imaging instruments, imaging spectrometers have spectral, radiometric and spatial characteristics and related requirements. Of these, uniformity, radiometric precision, and calibration have been identified as critically important for the science and application utility of imaging spectrometer instruments. These key requirements are enabling for the most advanced imaging spectrometer algorithms that retrieve parameters with units and quantifiable uncertainties. The current trend in imaging spectrometer instrumentation is for broader spectral coverage and wider swath while improving uniformity, precision, and calibration. A companion emphasis is for lower mass, power and volume, with instruments taking advantage of the latest detector, optical, electronics and computational technologies. The number of imaging spectrometers in use is increasing every year and this trend is on track to continue.

  8. Human resource leadership: the key to improved results in health.

    PubMed

    O'Neil, Mary L

    2008-06-20

    This article is the lead article in the Human Resources for Health journal's first quarterly feature. The series of seven articles has been contributed by Management Sciences for Health (MSH) under the theme of leadership and management in public health and will be published article by article over the next few weeks. The journal has invited Dr Manuel M. Dayrit, Director of the WHO Department of Human Resources for Health and former Minister of Health for the Philippines to launch the feature with an opening editorial to be found in the journal's blog. This opening article describes the human resource challenges that managers around the world report and analyses why solutions often fail to be implemented. Despite rising attention to the acute shortage of health care workers, solutions to the human resource (HR) crisis are difficult to achieve, especially in the poorest countries. Although we are aware of the issues and have developed HR strategies, the problem is that some old systems of leading and managing human resources for health do not work in today's context. The Leadership Development Program (LDP) is grounded on the belief that good leadership and management can be learned and practiced at all levels. The case studies in this issue were chosen to illustrate results from using the LDP at different levels of the health sector. The LDP makes a profound difference in health managers' attitudes towards their work. Rather than feeling defeated by a workplace climate that lacks motivation, hope, and commitment to change, people report that they are mobilized to take action to change the status quo. The lesson is that without this capacity at all levels, global policy and national HR strategies will fail to make a difference.

  9. 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.

  10. 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

  11. 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…

  12. One Key LOGO and Hands-On Activity Cards.

    ERIC Educational Resources Information Center

    Friesen, Chuck; And Others

    Developed to assist primary school teachers who wish to implement LOGO and One-Key LOGO (OKL) in their schools, this document consists of a LOGO resource manual and 92 color-coded activity cards designed to guide a pre-reader or primary child through a series of problem solving steps. After a brief introduction, which contains computer terminology…

  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. 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…

  15. 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…

  16. 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. PMID:27386254

  17. Key Informants' Perspectives on Accredited Breast Cancer Centres: Results of a Survey.

    PubMed

    Kowalski, C; Wesselmann, S; Ansmann, L; Kreienberg, R; Pfaff, H

    2012-03-01

    This paper presents the results of a survey among key informants that was conducted between June and September 2011 in Breast Cancer Centers that were accredited according to the criteria of the German Cancer Society (DKG). The survey intended to assess the degree to which the breast cancer center concept was accepted among the key informants as well as to gain an overview over structures and processes in the centers. The Questionnaire for Breast Cancer Centres Key Informants 2011 (FRIZ 2011) was used with two reminders having been sent out. Questionnaires were sent back from 149 of the 243 initially contacted hospitals (response rate: 61.3 %). The vast majority of respondents indicated to be part of the Breast Cancer Center management. 110 of the 149 hospitals did also participate in the patient survey conducted in 2010. Among the key informants surveyed, the concept is highly accepted with regard to improvements in patient care. Overall, the concept is regarded as "good" or "very good" by almost all respondents. Both contact to resident doctors and the hospitals' reputations improved since the implementation of the concept. Quality and patient safety were more often on the agenda than financial performance in the quality circles with the main co-operation partners of the Breast Cancer Centers. PMID:25308982

  18. Physical Activity and Obesity: Biomechanical and Physiological Key Concepts

    PubMed Central

    Nantel, Julie; Mathieu, Marie-Eve; Prince, François

    2011-01-01

    Overweight (OW) and obesity (OB) are often associated with low levels of physical activity. Physical activity is recommended to reduce excess body weight, prevent body weight regain, and decrease the subsequent risks of developing metabolic and orthopedic conditions. However, the impact of OW and OB on motor function and daily living activities must be taken into account. OW and OB are associated with musculoskeletal structure changes, decreased mobility, modification of the gait pattern, and changes in the absolute and relative energy expenditures for a given activity. While changes in the gait pattern have been reported at the ankle, knee, and hip, modifications at the knee level might be the most challenging for articular integrity. This review of the literature combines concepts and aims to provide insights into the prescription of physical activity for this population. Topics covered include the repercussions of OW and OB on biomechanical and physiological responses associated with the musculoskeletal system and daily physical activity. Special attention is given to the effect of OW and OB in youth during postural (standing) and various locomotor (walking, running, and cycling) activities. PMID:21113311

  19. Are the American Psychological Association's Detainee Interrogation Policies Ethical and Effective?: Key Claims, Documents, and Results.

    PubMed

    Pope, Kenneth S

    2011-01-01

    After 9-11, the United States began interrogating detainees at settings such as Abu Ghraib, Bagram, and Guantanamo. The American Psychological Association (APA) supported psychologists' involvement in interrogations, adopted formal policies, and made an array of public assurances. This article's purpose is to highlight key APA decisions, policies, procedures, documents, and public statements in urgent need of rethinking and to suggest questions that may be useful in a serious assessment, such as, "However well intended, were APA's interrogation policies ethically sound?"; "Were they valid, realistic, and able to achieve their purpose?"; "Were other approaches available that would address interrogation issues more directly, comprehensively, and actively, that were more ethically and scientifically based, and that would have had a greater likelihood of success?"; and "Should APA continue to endorse its post-9-11 detainee interrogation policies?"

  20. Key role for transketolase activity in erythritol production by Trichosporonoides megachiliensis SN-G42.

    PubMed

    Sawada, Katsuhiko; Taki, Arihiro; Yamakawa, Takashi; Seki, Minoru

    2009-11-01

    Erythritol is an important sugar alcohol industrially produced only by fermentation. The highly osmophilic yeast-like fungi, Trichosporonoides megachiliensis SN-G42, enables commercial production of erythritol with a high conversion from glucose to erythritol of more than 47%. However, the microbial production pathway of erythritol remains unclear. In the present study, the activities of enzymes in the pentose phosphate pathway of Trichosporonoides megachiliensis SN-G42 used for industrial erythritol production were measured under various culture conditions to examine the production mechanism and the key-enzymes. As a result, the various enzyme activities of this organism are revealed in the pentose phosphate pathway, i.e., those of hexokinase, glucose-6-phosphate dehydrogenase, gluconate dehydrogenase, transketolase, transaldolase, and erythrose reductase. In the cultures in which erythritol was produced after completion of cell growth, the enzyme activities of the pentose phosphate pathway were higher than those of the TCA cycle. In particular, transketolase activity was correlated with erythritol productivity under various production cultures with different agitation speeds and thiamine concentrations. These results suggest that erythritol may be produced mainly through the pentose phosphate pathway. In addition, the high activity of transketolase is required to produce abundant intermediates, which results in high erythritol productivity. As such, transketolase appears to be a key-enzyme for erythritol production in the organism studied.

  1. Electroencephalogram γ-band activity during the perception of music key levels.

    PubMed

    Ma, Weiyi; Lai, Yongxiu; Zheng, Xiaojing; Yang, Hua; Yao, Dezhong

    2013-03-01

    An interdisciplinary research field, music perception involves various disciplines, such as psychology, neuroscience, and even physics. Research on music perception offers us a window into the mechanism of the brain. In music perception, the same distance of key shift in different directions tends to be perceived as different degrees of change. It, however, still remains unclear whether directional asymmetry is specific to key shift perception or a general phenomenon of key perception. Using both behavioral and electroencephalogram methods, this study examined Chinese nonmusicians' subjective ratings and electroencephalogram γ-band activity related to a piece of music performed at three different key levels and presented in three separate performances, none of which contained a key shift. This study showed that directional asymmetry is a general phenomenon of key level perception rather than specific to key shift perception. Furthermore, a counterclockwisely modulated key is related to stronger γ-band spectral power than a clockwisely modulated key.

  2. 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.

  3. The HIT-II Spherical Torus: Physics and Key Experimental Results

    NASA Astrophysics Data System (ADS)

    Redd, A. J.; Hamp, W. T.; Izzo, V. A.; Jarboe, T. R.; Nelson, B. A.; O'Neill, R. G.; Raman, R.; Sieck, P. E.; Smith, R. J.

    2004-11-01

    Discharges in the HIT-II spherical torus device [Redd et al., Phys. Plasmas 9, 2006 (2002)] can be driven by either Ohmic or Coaxial Helicity Injection (CHI) current drive. A new CHI operating regime has been explored, with toroidal plasma currents of up to 350 kA, I_p/I_TF ratios of up to 1.2, and internal probing data which may demonstrate the formation of a closed-flux core. The key to acheiving these results is the magnetic field shear in the CHI injector region, with a minimum shear necessary for current build-up. Ohmic plasma performance has also improved, with peak currents up to 300 kA, with and without transient CHI startup. The CHI startup technique [Raman et al., Phys. Plasmas 11, 2565 (2004)] provides more robust discharges, with a wider operating space and more efficient use of the transformer Volt-seconds, than unassisted Ohmic. Finally, CHI can be used to enhance an Ohmic plasma current without significantly degrading the quality of the discharge. Results will be presented for each HIT--II operating regime, including empirical performance scalings and applicable parametric operating spaces.

  4. 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.

  5. Video summarization using descriptors of motion activity: a motion activity based approach to key-frame extraction from video shots

    NASA Astrophysics Data System (ADS)

    Divakaran, Ajay; Radhakrishnan, Regunathan; Peker, Kadir A.

    2001-10-01

    We describe a video summarization technique that uses motion descriptors computed in the compressed domain. It can either speed up conventional color-based video summarization techniques, or rapidly generate a key-frame based summary by itself. The basic hypothesis of the work is that the intensity of motion activity of a video segment is a direct indication of its `summarizability,' which we experimentally verify using the MPEG-7 motion activity descriptor and the fidelity measure proposed in H. S. Chang, S. Sull, and S. U. Lee, `Efficient video indexing scheme for content-based retrieval,' IEEE Trans. Circuits Syst. Video Technol. 9(8), (1999). Note that the compressed domain extraction of motion activity intensity is much simpler than the color-based calculations. We are thus able to quickly identify easy to summarize segments of a video sequence since they have a low intensity of motion activity. We are able to easily summarize these segments by simply choosing their first frames. We can then apply conventional color-based summarization techniques to the remaining segments. We thus speed up color-based summarization by reducing the number of segments processed. Our results also motivate a simple and novel key-frame extraction technique that relies on a motion activity based nonuniform sampling of the frames. Our results indicate that it can either be used by itself or to speed up color-based techniques as explained earlier.

  6. 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.

  7. 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.

  8. Alemtuzumab in the treatment of multiple sclerosis: key clinical trial results and considerations for use

    PubMed Central

    Horakova, Dana; Kovarova, Ivana

    2015-01-01

    Alemtuzumab is a humanized monoclonal antibody therapy that has recently been approved in over 30 countries for patients with active relapsing-remitting multiple sclerosis. It acts by targeting CD52, an antigen primarily expressed on T and B lymphocytes, resulting in their depletion and subsequent repopulation. The alemtuzumab clinical development program used an active comparator, subcutaneous interferon beta-1a, to show that alemtuzumab is a highly efficacious disease-modifying therapy, with benefits on relapses, disability outcomes, and freedom from clinical disease and magnetic resonance imaging activity. The safety profile was consistent across studies and no new safety signals have emerged during follow-up in the extension study. Infusion-associated reactions are common with alemtuzumab, but rarely serious. Infection incidence was elevated with alemtuzumab in clinical studies; most infections were mild or moderate in severity. Autoimmune adverse events occurred in approximately a third of patients, manifesting mainly as thyroid disorders, and less frequently as immune thrombocytopenia or nephropathy. A comprehensive monitoring program lasting at least 4 years after the last alemtuzumab dose allows early detection and effective management of autoimmune adverse events. Further experience with alemtuzumab in the clinic will provide needed long-term data. PMID:25584072

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

    PubMed Central

    Rashid, Shirya

    2009-01-01

    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. PMID:21160575

  10. Activities of key metabolic enzymes in the heater organs of scombroid fishes.

    PubMed

    Tullis, A; Block, B A; Sidell, B D

    1991-11-01

    Maximal in vitro activities of key metabolic enzymes were measured in brain and eye heaters of five species of scombroid fishes. Istiophorid billfishes (blue marlin, striped marlin and Mediterranean spearfish), xiphiid billfishes (Pacific and Mediterranean stocks) and a scombrid fish (butterfly mackerel) were included in the analysis. Our main objectives were (1) to assess the maximum possible substrate flux in heater tissue, and (2) to determine what metabolic substrates could fuel heat production. Heater tissue of all scombroids examined showed extremely high oxidative capacity. Activities of citrate synthase, a commonly measured index of oxidative metabolism, included the highest value ever reported for vertebrate tissue. In most billfishes, citrate synthase activities were similar to or higher than those found for mammalian cardiac and avian flight muscle. Marker enzymes for aerobic carbohydrate metabolism (hexokinase) and fatty acid metabolism (carnitine palmitoyltransferase and 3-hydroxyacyl-CoA dehydrogenase) also displayed extraordinarily high activities. Activities of carnitine palmitoyltransferase measured in heater organs were among the highest reported for vertebrates. These results indicate that heat production could be fueled aerobically by either lipid or carbohydrate metabolism. Inter- and intraspecifically, heater organs of fishes from the colder Mediterranean waters had a higher aerobic capacity and, hence, a greater heat-generating potential, than fishes from the warmer waters of the Pacific. This difference may be attributed to different thermal environments or it may result from allometry, since fishes caught in the Mediterranean were considerably smaller than those caught in the Pacific.

  11. 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…

  12. 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…

  13. Keying Results on the CELT-Structure Test to U.S. Grade Level Instructional Materials

    ERIC Educational Resources Information Center

    Moran, Ross T.

    1978-01-01

    It would be beneficial for ESL instructors to know the U.S. grade equivalent English ability of their students for placement purposes, especially if their instructional materials are keyed for U.S. classrooms. For this purpose, the Stanford Intermediate Level I Reading Comprehension Test was compared with the CELT-Structure Test. (Author/RM)

  14. 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…

  15. 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…

  16. 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

  17. 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

    2013-07-01

    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.

  18. 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

  19. 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

  20. [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. PMID:21438253

  1. Parvoviruses Cause Nuclear Envelope Breakdown by Activating Key Enzymes of Mitosis

    PubMed Central

    Porwal, Manvi; Cohen, Sarah; Snoussi, Kenza; Popa-Wagner, Ruth; Anderson, Fenja; Dugot-Senant, Nathalie; Wodrich, Harald; Dinsart, Christiane; Kleinschmidt, Jürgen A.; Panté, Nelly; Kann, Michael

    2013-01-01

    Disassembly of the nuclear lamina is essential in mitosis and apoptosis requiring multiple coordinated enzymatic activities in nucleus and cytoplasm. Activation and coordination of the different activities is poorly understood and moreover complicated as some factors translocate between cytoplasm and nucleus in preparatory phases. Here we used the ability of parvoviruses to induce nuclear membrane breakdown to understand the triggers of key mitotic enzymes. Nuclear envelope disintegration was shown upon infection, microinjection but also upon their application to permeabilized cells. The latter technique also showed that nuclear envelope disintegration was independent upon soluble cytoplasmic factors. Using time-lapse microscopy, we observed that nuclear disassembly exhibited mitosis-like kinetics and occurred suddenly, implying a catastrophic event irrespective of cell- or type of parvovirus used. Analyzing the order of the processes allowed us to propose a model starting with direct binding of parvoviruses to distinct proteins of the nuclear pore causing structural rearrangement of the parvoviruses. The resulting exposure of domains comprising amphipathic helices was required for nuclear envelope disintegration, which comprised disruption of inner and outer nuclear membrane as shown by electron microscopy. Consistent with Ca++ efflux from the lumen between inner and outer nuclear membrane we found that Ca++ was essential for nuclear disassembly by activating PKC. PKC activation then triggered activation of cdk-2, which became further activated by caspase-3. Collectively our study shows a unique interaction of a virus with the nuclear envelope, provides evidence that a nuclear pool of executing enzymes is sufficient for nuclear disassembly in quiescent cells, and demonstrates that nuclear disassembly can be uncoupled from initial phases of mitosis. PMID:24204256

  2. Identification of key neoculin residues responsible for the binding and activation of the sweet taste receptor

    PubMed Central

    Koizumi, Taichi; Terada, Tohru; Nakajima, Ken-ichiro; Kojima, Masaki; Koshiba, Seizo; Matsumura, Yoshitaka; Kaneda, Kohei; Asakura, Tomiko; Shimizu-Ibuka, Akiko; Abe, Keiko; Misaka, Takumi

    2015-01-01

    Neoculin (NCL) is a heterodimeric protein isolated from the edible fruit of Curculigo latifolia. It exerts a taste-modifying activity by converting sourness to sweetness. We previously demonstrated that NCL changes its action on the human sweet receptor hT1R2-hT1R3 from antagonism to agonism as the pH changes from neutral to acidic values, and that the histidine residues of NCL molecule play critical roles in this pH-dependent functional change. Here, we comprehensively screened key amino acid residues of NCL using nuclear magnetic resonance (NMR) spectroscopy and alanine scanning mutagenesis. We found that the mutations of Arg48, Tyr65, Val72 and Phe94 of NCL basic subunit increased or decreased both the antagonist and agonist activities. The mutations had only a slight effect on the pH-dependent functional change. These residues should determine the affinity of NCL for the receptor regardless of pH. Their locations were separated from the histidine residues responsible for the pH-dependent functional change in the tertiary structure. From these results, we concluded that NCL interacts with hT1R2-hT1R3 through a pH-independent affinity interface including the four residues and a pH-dependent activation interface including the histidine residues. Thus, the receptor activation is induced by local structural changes in the pH-dependent interface. PMID:26263392

  3. 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.

  4. 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

  5. Src activation by β-adrenoreceptors is a key switch for tumour metastasis.

    PubMed

    Armaiz-Pena, Guillermo N; Allen, Julie K; Cruz, Anthony; Stone, Rebecca L; Nick, Alpa M; Lin, Yvonne G; Han, Liz Y; Mangala, Lingegowda S; Villares, Gabriel J; Vivas-Mejia, Pablo; Rodriguez-Aguayo, Cristian; Nagaraja, Archana S; Gharpure, Kshipra M; Wu, Zheng; English, Robert D; Soman, Kizhake V; Shahzad, Mian M K; Shazhad, Mian M K; Zigler, Maya; Deavers, Michael T; Zien, Alexander; Soldatos, Theodoros G; Jackson, David B; Wiktorowicz, John E; Torres-Lugo, Madeline; Young, Tom; De Geest, Koen; Gallick, Gary E; Bar-Eli, Menashe; Lopez-Berestein, Gabriel; Cole, Steve W; Lopez, Gustavo E; Lutgendorf, Susan K; Sood, Anil K

    2013-01-01

    Noradrenaline can modulate multiple cellular functions important for cancer progression; however, how this single extracellular signal regulates such a broad array of cellular processes is unknown. Here we identify Src as a key regulator of phosphoproteomic signalling networks activated in response to beta-adrenergic signalling in cancer cells. These results also identify a new mechanism of Src phosphorylation that mediates beta-adrenergic/PKA regulation of downstream networks, thereby enhancing tumour cell migration, invasion and growth. In human ovarian cancer samples, high tumoural noradrenaline levels were correlated with high pSrc(Y419) levels. Moreover, among cancer patients, the use of beta blockers was significantly associated with reduced cancer-related mortality. Collectively, these data provide a pivotal molecular target for disrupting neural signalling in the tumour microenvironment.

  6. 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

  7. Building an Evaluative Culture: The Key to Effective Evaluation and Results Management

    ERIC Educational Resources Information Center

    Mayne, John

    2009-01-01

    As many reviews of results-based performance systems have noted, a weak evaluative culture in an organization undermines attempts at building an effective evaluation and/or results management regime. This article sets out what constitutes a strong evaluative culture where information on performance results is deliberately sought in order to learn…

  8. 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.

  9. Lunar maria - result of mantle plume activity?

    NASA Astrophysics Data System (ADS)

    Sharkov, E.

    It is generally accepted that lunar maria are the result of catastrophic impact events. However, comparative studying of the Earth's and the Moon's tectonomagmatic evolution could evidence about another way of these specific structures origin. Such studies showed that the both planetary bodies evolved on the close scenario: their geological development began after solidification of global magmatic oceans which led to appearance of their primordial crusts: granitic on the Earth and anorthositic - on the Moon. The further evolution of the both bodies occurred in two stages. For their first stages, lasted ˜2.5 mlrd. years on the Earth and ˜1.5 mlrd. years on the Moon, were typical melts, generated in depleted mantle (Bogatikov et al., 2000). However, at the boundary 2.2-2.0 Ga ago on the Earth and 3.9-3.8 Ga on the Moon another type of magmas appeared: geochemical enriched Fe-Ti picrites and basalts, characteristic for the terrestrial Phanerozoic plume-related situations, and basaltic mare magmatism with high-Ti varieties on the Moon. It suggests that evolution of the Earth's magmatism was linked with ascending of mantle plumes (superplumes) of two generation: (1) generated in the mantle, depleted during solidification of magmatic ocean and Archean magmatic activity, and (2) generated at the core-mantle boundary (CMB). The latter were enriched in the mantle fluid components (Fe, Ti, alkalies, etc); this lighter material could ascend to shallower depths, leading to change of tectonic processes, in particular, to appearance of plate tectonics as the major type of tectonomagmatic activity till now (Bogatikov et al., 2000). By analogy to the Earth, magmatism of the Moon was also linked with ascending of mantle plumes: (1) generated in the depleted mantle (magnesian suite) and (2) generated at the lunar CMB with liquid at that time metallic core (mare basalt and picrites with high-Ti varieties). Like on the Earth, these plumes were lighter than the older plumes, and

  10. The 'Vertical Structure and Diabatic Processes of the Madden-Julian Oscillation' model evaluation project: Overview and key results (Invited)

    NASA Astrophysics Data System (ADS)

    Klingaman, N. P.; Jiang, X.; Xavier, P.; Petch, J.; Waliser, D. E.; Woolnough, S.

    2013-12-01

    -level temperature and humidity, evaluated against YoTC analyses, within 48 hours. These biases stem from large differences in cloud cover above the freezing level in models, which lead to discrepancies in the magnitude and even sign of the radiative temperature increments; this points to errors in cloud-radiative interactions in these models. In the 20-day hindcasts, there is no relationship between a model's ability to predict the MJO and its vertical profile of diabatic heating; models with similar diabatic-heating profiles have very different levels of skill in these hindcasts. A more consistent association is found between MJO skill and diabatic-moistening profiles, with high-skill models showing a clear transition from shallow moistening in suppressed conditions to deep moistening during the active phase. We will present an overview of the evaluation project, its goals and objectives; highlight key results from each components of the project; and discuss the next steps for further analysis, including the dissemination of data to the wider community.

  11. 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

  12. 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

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

    PubMed

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

    PubMed

    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.

  15. Phosphorylation of WASp is a key regulator of activity and stability in vivo

    PubMed Central

    Blundell, Michael P.; Bouma, Gerben; Metelo, Joao; Worth, Austen; Calle, Yolanda; Cowell, Lucy A.; Westerberg, Lisa S.; Moulding, Dale A.; Mirando, Samuel; Kinnon, Christine; Cory, Giles O.; Jones, Gareth E.; Snapper, Scott B.; Burns, Siobhan O.; Thrasher, Adrian J.

    2009-01-01

    The Wiskott-Aldrich syndrome protein (WASp) is a key cytoskeletal regulator in hematopoietic cells. Covalent modification of a conserved tyrosine by phosphorylation has emerged as an important potential determinant of activity, although the physiological significance remains uncertain. In a murine knockin model, mutation resulting in inability to phosphorylate Y293 (Y293F) mimicked many features of complete WASp-deficiency. Although a phosphomimicking mutant Y293E conferred enhanced actin-polymerization, the cellular phenotype was similar due to functional dysregulation. Furthermore, steady-state levels of Y293E-WASp were markedly reduced compared to wild-type WASp and Y293F-WASp, although partially recoverable by treatment of cells with proteasome inhibitors. Consequently, tyrosine phosphorylation plays a critical role in normal activation of WASp in vivo, and is indispensible for multiple tasks including proliferation, phagocytosis, chemotaxis, and assembly of adhesion structures. Furthermore, it may target WASp for proteasome-mediated degradation, thereby providing a default mechanism for self-limiting stimulation of the Arp2/3 complex. PMID:19805221

  16. 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.

  17. Determination of ideal-gas enthalpies of formation for key compounds: The 1988 project results

    SciTech Connect

    Steele, W.V.; Chirico, R.D.; Nguyen, A.; Hossenlopp, I.A.; Smith, N.K.

    1990-07-01

    The results of a study aimed at improvement of group contribution methodology for estimation of thermodynamic properties of organic substances are reported. Specific weakness 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 the condensed phase and vapor-pressure measurements. Ideal-gas enthalpies of formation are reported for 3-methylbuta-1,2-diene; 2,5-dimethylhexa-2,4-diene; acetaldoxime; N,N-diethylhydroxylamine; 1-methylpyrrolidin-2-one; and phenanthrene. Solid and liquid-phase enthalpies of formation at 298.15 K are determined for benzamide. Ring corrections, group terms, and next-nearest-neighbor interaction terms useful in the application of group contribution correlations are derived. 54 refs., 2 figs., 21 tabs.

  18. Determination of ideal-gas enthalpies of formation for key compounds: The 1988 project results

    NASA Astrophysics Data System (ADS)

    Steele, W. V.; Chirico, R. D.; Nguyen, A.; Hossenlopp, I. A.; Smith, N. K.

    1990-07-01

    The results of a study aimed at improvement of group contribution methodology for estimation of thermodynamic properties of organic substances are reported. Specific weakness 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 the condensed phase and vapor pressure measurements. Ideal-gas enthalpies of formation are reported for 3-methylbuta 1,2-diene; 2,5-dimethylhexa 2,4-diene; acetaldoxime; N,N-diethyl hydroxylamine; 1-methylpyrrolidin-2-one; and phenanthrene. Solid and liquid phase enthalpies of formation at 298.15 K are determined for benzamide. Ring corrections, group terms, and next-nearest-neighbor interaction terms useful in the application of group contribution correlations are derived.

  19. 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

  20. Determination of ideal-gas enthalpies of formation for key compounds: The 1989 project results

    NASA Astrophysics Data System (ADS)

    Steele, W. V.; Chirico, R. D.; Nguyen, A.; Hossenlopp, I. A.; Smith, N. K.

    1991-10-01

    The results of a study aimed at improvement of group-contribution methodology for estimation of thermodynamic properties of organic and organosilicon 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 the condensed phase, vapor pressure measurements, and differential scanning calorimetric (dsc) heat capacity measurements. Ideal gas enthalpies of formation of (+ or -) butan-2-ol, tetradecan-1-ol, hexan-1,6-diol, methacrylamide, benzoyl formic acid, naphthalene 2,6-dicarboxylic acid dimethyl ester, and tetraethylsilane are reported. A crystalline-phase enthalpy of formation at 298.15 K was determined for naphthalene-2,6-dicarboxylic acid, which decomposed at 695 K before melting. The combustion calorimetry of tetraethylsilane used the proven fluorine-additivity methodology. Critical temperature and critical density were determined for tetraethylsilane with differential scanning calorimeter and the critical pressure was derived. Group additivity parameters useful in the application of group contribution correlations are derived.

  1. Experimental demonstration of an active phase randomization and monitor module for quantum key distribution

    NASA Astrophysics Data System (ADS)

    Sun, Shi-Hai; Liang, Lin-Mei

    2012-08-01

    Phase randomization is a very important assumption in the BB84 quantum key distribution (QKD) system with weak coherent source; otherwise, eavesdropper may spy the final key. In this Letter, a stable and monitored active phase randomization scheme for the one-way and two-way QKD system is proposed and demonstrated in experiments. Furthermore, our scheme gives an easy way for Alice to monitor the degree of randomization in experiments. Therefore, we expect our scheme to become a standard part in future QKD systems due to its secure significance and feasibility.

  2. 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.

  3. 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.

  4. 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

  5. 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

  6. Arctigenic acid, the key substance responsible for the hypoglycemic activity of Fructus Arctii.

    PubMed

    Xu, Zhaohui; Gu, Chenchen; Wang, Kai; Ju, Jiaxing; Wang, Haiying; Ruan, Kefeng; Feng, Yi

    2015-01-15

    We have reported the antidiabetic activity of the total lignans from Fructus arctii (TLFA) against alloxan-induced diabetes in mice and rats. In this study, arctigenic acid was found to be the main metabolite in rat plasma detected by UPLC/MS and HPLC/MS/MS after oral administration of TLFA. For the first time, its hypoglycemic activity and acute oral toxicity were evaluated in Goto-Kakizaki (GK) rats, a spontaneous type 2 diabetic animal model, and ICR mice respectively. GK rats were orally given arctigenic acid (50 mg/kg) twice daily before each meal for 12 weeks. The treatment reduced the elevated plasma glucose, glycosylated hemoglobin and showed significant improvement in glucose tolerance in glucose fed hyperglycemic GK rats. We found that the hypoglycemic effect of arctigenic acid was partly due to the stimulation on insulin secretion, whereas the body weight was not affected by arctigenic acid administration in GK rats. Meanwhile, there was no observable acute toxicity of arctigenic acid treatment at the dosage of 280 mg/kg body weight daily in the acute 14-day toxicity study in mice. This study demonstrates that arctigenic acid may be the main metabolite in the rat serum after oral administration of TLFA, which showed significant hypoglycemic effect in GK rats, and low acute toxicity in ICR mice. The result prompts us that arctigenic acid is the key substance responsible for Fructus Arctii antidiabetic activity and it has a great potential to be further developed as a novel therapeutic agent for diabetes in humans.

  7. Arctigenic acid, the key substance responsible for the hypoglycemic activity of Fructus Arctii.

    PubMed

    Xu, Zhaohui; Gu, Chenchen; Wang, Kai; Ju, Jiaxing; Wang, Haiying; Ruan, Kefeng; Feng, Yi

    2015-01-15

    We have reported the antidiabetic activity of the total lignans from Fructus arctii (TLFA) against alloxan-induced diabetes in mice and rats. In this study, arctigenic acid was found to be the main metabolite in rat plasma detected by UPLC/MS and HPLC/MS/MS after oral administration of TLFA. For the first time, its hypoglycemic activity and acute oral toxicity were evaluated in Goto-Kakizaki (GK) rats, a spontaneous type 2 diabetic animal model, and ICR mice respectively. GK rats were orally given arctigenic acid (50 mg/kg) twice daily before each meal for 12 weeks. The treatment reduced the elevated plasma glucose, glycosylated hemoglobin and showed significant improvement in glucose tolerance in glucose fed hyperglycemic GK rats. We found that the hypoglycemic effect of arctigenic acid was partly due to the stimulation on insulin secretion, whereas the body weight was not affected by arctigenic acid administration in GK rats. Meanwhile, there was no observable acute toxicity of arctigenic acid treatment at the dosage of 280 mg/kg body weight daily in the acute 14-day toxicity study in mice. This study demonstrates that arctigenic acid may be the main metabolite in the rat serum after oral administration of TLFA, which showed significant hypoglycemic effect in GK rats, and low acute toxicity in ICR mice. The result prompts us that arctigenic acid is the key substance responsible for Fructus Arctii antidiabetic activity and it has a great potential to be further developed as a novel therapeutic agent for diabetes in humans. PMID:25636881

  8. 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.

  9. 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

  10. Exercise as Medicine: Key Concepts in Discussing Physical Activity with Patients who have Type 2 Diabetes.

    PubMed

    Armstrong, Marni J; Sigal, Ronald J

    2015-12-01

    People with type 2 diabetes stand to benefit substantially from being physically active. Practice guidelines consistently recommend that people with diabetes obtain at least 150 minutes of moderate to vigorous aerobic exercise per week. Although the message of 150 minutes per week is important, there are several other key messages regarding physical activity that may not be communicated as often or as clearly. This article gives an overview of the importance of resistance training, the dose-response relationship between physical activity and health outcomes, and the emerging evidence concerning the role of sedentary behavior in people with type 2 diabetes. This article provides valuable content for healthcare providers that will help to inform their discussions about physical activity with patients who have type 2 diabetes.

  11. Key Role of Ubc5 and Lysine-63 Polyubiquitination in Viral Activation of IRF3

    PubMed Central

    Zeng, Wenwen; Xu, Ming; Liu, Siqi; Sun, Lijun; Chen, Zhijian J.

    2009-01-01

    SUMMARY The mitochondrial antiviral signaling protein (MAVS; also known as IPS-1, VISA and CARDIF) is essential for innate immune response against RNA viruses. MAVS transduces signals from the cytosolic RIG-I-like receptors, which bind to viral RNAs, but how MAVS activates downstream transcription factors such as IRF3 to induce type-I interferons is not well understood. We have established a cell-free system in which mitochondria derived from virus-infected cells activates IRF3 in the cytosol. Fractionation of the cytosol led to the identification of Ubc5 as a ubiquitin-conjugating enzyme (E2) required for IRF3 activation. Using an inducible RNAi strategy, we demonstrate that catalytically active Ubc5 is required for IRF3 activation by viral infection. The activation of IRF3 also requires two ubiquitin-binding domains of NEMO. Furthermore, we show that replacement of endogenous ubiquitin with its K63R mutant abolishes viral activation of IRF3, demonstrating that K63 polyubiquitination plays a key role in IRF3 activation. PMID:19854139

  12. Laser spark ignition of premixed methane-air mixtures: parameter measurements and determination of key factors for ultimate ignition results.

    PubMed

    Li, Xiaohui; Smith, Benjamin W; Omenetto, Nicoló

    2014-01-01

    In this study, we present an experimental investigation of the parameters of the laser spark ignition of premixed methane-air mixtures and the determination of the key factors for the ultimate ignition result. Ignition is achieved in a mesh honeycomb burner using the 1064 nm output of a neodymium-doped yttrium aluminum garnet (Nd : YAG) laser. All pertinent laser ignition parameters, including the minimum ignition energy, the ignition time and blow out time, and the effects that the variation of experimental conditions, such as the spark energy, ignition position, equivalence ratio (ER), and flow rate, have on these parameters have been addressed systematically. To identify the key factors for the ultimate result of laser ignition, several parameters of the ignition processes are measured simultaneously, with an emphasis given to the temporal behavior of the hydroxyl (OH) radicals in relation to the data regarding the spark energy and the local ER. A clear finding of the study is that successful ignition events are always related to higher OH radical photon emissions, considered to be proportional to the concentration level of the OH radicals present, thus indicating a direct link between the OH level at early times (on a microsecond scale) and the ultimate result of laser ignition. Two-dimensional correlation plots of the spark energy, local ER, and OH radical photon count at early times with the ultimate results of laser ignition indicate that the spark energy and local ER do not play a critical role in determining the success or failure of the ignition and that the OH concentration in the early time range is the key factor in determining the final fate of laser ignition. Finally, on the basis of the results obtained here and in the existing literature, some considerations of the mechanism of laser ignition are presented. PMID:25226251

  13. Key factor in rice husk Ash/CaO sorbent for high flue gas desulfurization activity.

    PubMed

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

    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 factorfor 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, x1 (6-16 h), amount of RHA, x2 (5-15 g), amount of CaO, x3 (2-6 g), amount of water, x4 (90-110 mL), and hydration temperature, x5 (150-250 degrees C). The mathematical model developed was subjected to statistical tests and the model is adequate for predicting the SO2 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.

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

    PubMed Central

    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. PMID:25185230

  15. 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.

  16. Key beliefs related to decisions for physical activity engagement among first-in-family students transitioning to university.

    PubMed

    Cowie, Eloise; Hamilton, Kyra

    2014-08-01

    The current study investigated key beliefs related to decisions for physical activity (PA) engagement among first-in-family (FIF) students transitioning to university. FIF students (n = 157) completed an online questionnaire assessing standard theory of planned behaviour constructs and belief-based items. One week later, participants completed a follow-up questionnaire assessing self-reported PA during the previous week. Results identified a range of behavioural, normative, and control beliefs that were significantly correlated with both PA intention and behaviour. Various key beliefs were also identified in relation to FIF students' decisions to be regularly physically active, with behavioural beliefs such as "take up too much time", normative beliefs including "friends outside of university", and control beliefs such as "cost", identified. Finally, frequencies of those who strongly or fully accepted these beliefs were analysed, demonstrating that typically, a large number of FIF students did not hold the beliefs, and as such, these are relevant to target in resultant interventions. The current study effectively highlights a number of key beliefs that can be targeted in programs aimed at encouraging FIF students' PA. Further, the study addresses a gap in the literature of targeting FIF students, a cohort at risk for inactivity, and utilises a sound theoretical framework to identify the unique set of beliefs guiding decisions for PA for this at-risk community group. PMID:24381124

  17. Key beliefs related to decisions for physical activity engagement among first-in-family students transitioning to university.

    PubMed

    Cowie, Eloise; Hamilton, Kyra

    2014-08-01

    The current study investigated key beliefs related to decisions for physical activity (PA) engagement among first-in-family (FIF) students transitioning to university. FIF students (n = 157) completed an online questionnaire assessing standard theory of planned behaviour constructs and belief-based items. One week later, participants completed a follow-up questionnaire assessing self-reported PA during the previous week. Results identified a range of behavioural, normative, and control beliefs that were significantly correlated with both PA intention and behaviour. Various key beliefs were also identified in relation to FIF students' decisions to be regularly physically active, with behavioural beliefs such as "take up too much time", normative beliefs including "friends outside of university", and control beliefs such as "cost", identified. Finally, frequencies of those who strongly or fully accepted these beliefs were analysed, demonstrating that typically, a large number of FIF students did not hold the beliefs, and as such, these are relevant to target in resultant interventions. The current study effectively highlights a number of key beliefs that can be targeted in programs aimed at encouraging FIF students' PA. Further, the study addresses a gap in the literature of targeting FIF students, a cohort at risk for inactivity, and utilises a sound theoretical framework to identify the unique set of beliefs guiding decisions for PA for this at-risk community group.

  18. 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.

  19. 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. PMID:21270449

  20. 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.

  1. Subchronic exposure to leachate activates key markers linked with neurological disorder in Wistar male rat.

    PubMed

    Akintunde, J K; Oboh, G

    2015-12-01

    The linking of various environmental chemicals exposure to neurodegenerative disorders is current. This study was undertaken to elucidate the toxic effects and the underlying biochemical mechanism of leachate obtained from Elewi Odo municipal battery recycling site (EOMABRL) using key markers of neuronal damage in rat via an oral route. Analysis of the concentrations of heavy metals showed that lead, cadmium, nickel, chromium, manganese, and iron were higher than the acceptable limits set by the regulatory authority-the World Health Organization. Whereas, copper, zinc, and cobalt were lower than permissible limits. EOMABRL was administered at 0, 20, 40, 60, 80, and 100% concentrations to adult male rats for 60 days. An in vitro study was also carried out in the cerebellum to assess cholinesterase biochemistry assays. Following exposure, brain was collected to determine the antioxidant status. EOMABRL administration significantly increased superoxide dismutase (SOD) and catalase (CAT) activities, and a sequential decrease in reduced glutathione (GSH) level with a concomitant increase in the accumulation of hydrogen peroxide (H2O2) and malondialdehyde (MDA) level was observed, when compared with the control. The treated rat had a significant (P < 0.05) increase in the activities of acetycholinesterase (AChE) and butyrylcholinesterase (BuChE). Taken together, these findings conclude that some possible mechanisms by which EOMABRL elicits neuronal disorder in male rat could be through the activation of AChE and BuChE and induction of oxidative stress with necrosis of neuronal cells. PMID:26362636

  2. Activities of key enzymes in sucrose-to-starch conversion in wheat grains subjected to water deficit during grain filling.

    PubMed

    Yang, Jianchang; Zhang, Jianhua; Wang, Zhiqing; Xu, Guowei; Zhu, Qingsen

    2004-07-01

    This study tested the hypothesis that a controlled water deficit during grain filling of wheat (Triticum aestivum) could accelerate grain-filling rate through regulating the key enzymes involved in Suc-to-starch pathway in the grains. Two high lodging-resistant wheat cultivars were field grown. Well-watered and water-deficit (WD) treatments were imposed from 9 DPA until maturity. The WD promoted the reallocation of prefixed 14C from the stems to grains, shortened the grain-filling period, and increased grain-filling rate or starch accumulation rate (SAR) in the grains. Activities of Suc synthase (SuSase), soluble starch synthase (SSS), and starch branching enzyme (SBE) in the grains were substantially enhanced by WD and positively correlated with the SAR. ADP Glc pyrophosphorylase activity was also enhanced in WD grains initially and correlated with SAR with a smaller coefficient. Activities of granule-bound starch synthase and soluble and insoluble acid invertase in the grains were less affected by WD. Abscisic acid (ABA) content in the grains was remarkably enhanced by WD and very significantly correlated with activities of SuSase, SSS, and SBE. Application of ABA on well-watered plants showed similar results as those by WD. Spraying with fluridone, an ABA synthesis inhibitor, had the opposite effect. The results suggest that increased grain-filling rate is mainly attributed to the enhanced sink activity by regulating key enzymes involved in Suc-to-starch conversion, especially SuSase, SSS, and SBE, in wheat grains when subjected to a mild water deficit during grain filling, and ABA plays a vital role in the regulation of this process.

  3. Educational Consequences of Developmental Speech Disorder: Key Stage 1 National Curriculum Assessment Results in English and Mathematics

    ERIC Educational Resources Information Center

    Nathan, L.; Stackhouse, J.; Goulandris, N.; Snowling, M.J.

    2004-01-01

    Background: Children with speech difficulties may have associated educational problems. This paper reports a study examining the educational attainment of children at Key Stage 1 of the National Curriculum who had previously been identified with a speech difficulty. Aims: (1) To examine the educational attainment at Key Stage 1 of children…

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

    PubMed

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

    2016-01-20

    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.

  5. 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

  6. 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

  7. Active zone protein expression changes at the key stages of cerebellar cortex neurogenesis in the rat.

    PubMed

    Juranek, Judyta Karolina; Mukherjee, Konark; Siddiqui, Tabrez J; Kaplan, Benjamin J; Li, Jia Yi; Ahnert-Hilger, Gudrun; Jahn, Reinhard; Calka, Jaroslaw

    2013-07-01

    Signal transduction and neurotransmitter release in the vertebrate central nervous system are confined to the structurally complex presynaptic electron dense projections called "active zones." Although the nature of these projections remains a mystery, genetic and biochemical work has provided evidence for the active zone (AZ) associated proteins i.e. Piccolo/Aczonin, Bassoon, RIM1/Unc10, Munc13/Unc13, Liprin-α/SYD2/Dliprin and ELKS/CAST/BRP and their specific molecular functions. It still remains unclear, however, what their precise contribution is to the AZ assembly. In our project, we studied in Wistar rats the temporal and spatial distribution of AZ proteins and their colocalization with Synaptophysin in the developing cerebellar cortex at key stages of cerebellum neurogenesis. Our study demonstrated that AZ proteins were already present at the very early stages of cerebellar neurogenesis and exhibited distinct spatial and temporal variations in immunoexpression throughout the course of the study. Colocalization analysis revealed that the colocalization pattern was time-dependent and different for each studied protein. The highest collective mean percentage of colocalization (>85%) was observed at postnatal day (PD) 5, followed by PD10 (>83%) and PD15 (>80%). The findings of our study shed light on AZ protein immunoexpression changes during cerebellar cortex neurogenesis and help frame a hypothetical model of AZ assembly.

  8. CDK6 as a key regulator of hematopoietic and leukemic stem cell activation.

    PubMed

    Scheicher, Ruth; Hoelbl-Kovacic, Andrea; Bellutti, Florian; Tigan, Anca-Sarmiza; Prchal-Murphy, Michaela; Heller, Gerwin; Schneckenleithner, Christine; Salazar-Roa, María; Zöchbauer-Müller, Sabine; Zuber, Johannes; Malumbres, Marcos; Kollmann, Karoline; Sexl, Veronika

    2015-01-01

    The cyclin-dependent kinase 6 (CDK6) and CDK4 have redundant functions in regulating cell-cycle progression. We describe a novel role for CDK6 in hematopoietic and leukemic stem cells (hematopoietic stem cells [HSCs] and leukemic stem cells [LSCs]) that exceeds its function as a cell-cycle regulator. Although hematopoiesis appears normal under steady-state conditions, Cdk6(-/-) HSCs do not efficiently repopulate upon competitive transplantation, and Cdk6-deficient mice are significantly more susceptible to 5-fluorouracil treatment. We find that activation of HSCs requires CDK6, which interferes with the transcription of key regulators, including Egr1. Transcriptional profiling of HSCs is consistent with the central role of Egr1. The impaired repopulation capacity extends to BCR-ABL(p210+) LSCs. Transplantation with BCR-ABL(p210+)-infected bone marrow from Cdk6(-/-) mice fails to induce disease, although recipient mice do harbor LSCs. Egr1 knock-down in Cdk6(-/-) BCR-ABL(p210+) LSKs significantly enhances the potential to form colonies, underlining the importance of the CDK6-Egr1 axis. Our findings define CDK6 as an important regulator of stem cell activation and an essential component of a transcriptional complex that suppresses Egr1 in HSCs and LSCs.

  9. CDK6 as a key regulator of hematopoietic and leukemic stem cell activation

    PubMed Central

    Scheicher, Ruth; Hoelbl-Kovacic, Andrea; Bellutti, Florian; Tigan, Anca-Sarmiza; Prchal-Murphy, Michaela; Heller, Gerwin; Schneckenleithner, Christine; Salazar-Roa, María; Zöchbauer-Müller, Sabine; Zuber, Johannes; Malumbres, Marcos; Kollmann, Karoline

    2015-01-01

    The cyclin-dependent kinase 6 (CDK6) and CDK4 have redundant functions in regulating cell-cycle progression. We describe a novel role for CDK6 in hematopoietic and leukemic stem cells (hematopoietic stem cells [HSCs] and leukemic stem cells [LSCs]) that exceeds its function as a cell-cycle regulator. Although hematopoiesis appears normal under steady-state conditions, Cdk6−/− HSCs do not efficiently repopulate upon competitive transplantation, and Cdk6-deficient mice are significantly more susceptible to 5-fluorouracil treatment. We find that activation of HSCs requires CDK6, which interferes with the transcription of key regulators, including Egr1. Transcriptional profiling of HSCs is consistent with the central role of Egr1. The impaired repopulation capacity extends to BCR-ABLp210+ LSCs. Transplantation with BCR-ABLp210+–infected bone marrow from Cdk6−/− mice fails to induce disease, although recipient mice do harbor LSCs. Egr1 knock-down in Cdk6−/− BCR-ABLp210+ LSKs significantly enhances the potential to form colonies, underlining the importance of the CDK6-Egr1 axis. Our findings define CDK6 as an important regulator of stem cell activation and an essential component of a transcriptional complex that suppresses Egr1 in HSCs and LSCs. PMID:25342715

  10. Key amino acid residues for the endo-processive activity of GH74 xyloglucanase.

    PubMed

    Matsuzawa, Tomohiko; Saito, Yuji; Yaoi, Katsuro

    2014-05-01

    Unlike endo-dissociative-xyloglucanases, Paenibacillus XEG74 is an endo-processive xyloglucanase that contains four unique tryptophan residues in the negative subsites (W61 and W64) and the positive subsites (W318 and W319), as indicated by three-dimensional homology modelling. Selective replacement of the positive subsite residues with alanine mutations reduced the degree of processive activity and resulted in the more endo-dissociative-activity. The results showed that W318 and W319, which are found in the positive subsites, are essential for processive degradation and are responsible for maintaining binding interactions with xyloglucan polysaccharide through a stacking effect. PMID:24657616

  11. 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.

  12. Loss of delta-6-desaturase activity as a key factor in aging.

    PubMed

    Horrobin, D F

    1981-09-01

    Aging is characterized by a wide variety of defects, particularly in the cardiovascular and immune systems. Cyclic AMP levels fall, especially in lymphocytes. Delta-6-desaturase (D6D) levels have been found to fall rapidly in the testes and more slowly in the liver in aging rats. D6D is an enzyme which converts cis-linoleic acid to gamma-linolenic acid (GLA). Other factors which inhibit D6D activity are diabetes, alcohol and radiation, all of which may be associated with accelerated aging. In meat eaters or omnivores which can acquire arachidonic acid from food, the main consequences of D6D loss will be deficiencies of GLA, dihomogamma-linolenic acid (DGLA) and prostaglandin (PG) E1. PGE1 activates T lymphocytes, inhibits smooth muscle proliferation and thrombosis, is important in gonadal function and raises cyclic AMP levels in many tissues. It is a good candidate for a key factor lost in aging. Moderate food restriction, the only manoeuvre which consistently slows aging in homoiotherms, raises D6D activity by 300%. Other factors important in regulating D6D and the conversion of GLA to PGE1 are zinc, pyridoxine, ascorbic acid, the pineal hormone, melatonin, and possibly vitamin B3. GLA administration to humans has been found to lower blood pressure and cholesterol, and to cause clinical improvement in patients with Sjogren's syndrome, scleroderma and alcoholism. These diseases are associated with some features of accelerated aging. The proposition that D6D loss is not only a marker of aging but a cause of some of its major manifestations is amenable to experimental test even in humans. The blocked enzyme can be by-passed by giving GLA directly.

  13. 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.

  14. 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; 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 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

  15. 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.

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

    PubMed

    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, [Formula: see text], 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.

  17. 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

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

    PubMed

    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, [Formula: see text], 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

  19. 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).

  20. 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

  1. 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.; Chen, Kuan-Bei; Stonestrom, Aaron; Long, Maria; Keller, Cheryl A.; Cheng, Yong; Jain, Deepti; Visel, Axel; et al

    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

  2. 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.

  3. 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

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

    PubMed

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

    2015-03-01

    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.

  5. 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.

  6. 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. PMID:25479573

  7. Receptor density is key to the alpha2/beta interferon differential activities.

    PubMed

    Moraga, Ignacio; Harari, Daniel; Schreiber, Gideon; Uzé, Gilles; Pellegrini, Sandra

    2009-09-01

    Multiple type I interferons (IFN-alpha/beta) elicit Jak/Stat activation, rapid gene induction, and pleiotropic effects, such as differentiation, antiviral protection, and blocks in proliferation, which are dependent on the IFN subtype and the cellular context. To date, ligand- and receptor-specific molecular determinants underlying IFN-alpha/beta differential activities or potencies have been well characterized. To analyze cellular determinants that impact subtype-specific potency, human fibrosarcoma U5A-derived clones, exhibiting a gradient of IFN sensitivity by virtue of increasing receptor levels, were monitored for Jak/Stat signaling, gene induction, cell cycle lengthening, and apoptosis. In cells with scarce receptors, IFN-beta was more potent than IFN-alpha2 in antiproliferative activity, while the two subtypes were equipotent in all other readouts. Conversely, in cells with abundant receptors, IFN-alpha2 matched or even surpassed IFN-beta in all readouts tested. Our results suggest that the differential activities of the IFN subtypes are dictated not only by the intrinsic ligand/receptor binding kinetics but also by the density of cell surface receptor components.

  8. 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. PMID:25568077

  9. 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

  10. National Low-Level Waste Management Program final summary report of key activities and accomplishments for fiscal year 1996

    SciTech Connect

    Garcia, R.S.

    1996-12-01

    To assist the Department of Energy (DOE) in fulfilling its responsibilities under the Low-Level Radioactive Waste Policy Amendments Act of 1985, the National Low-Level Waste Management Program (NLLWMP) outlines the key activities tat the NLLWMP will accomplish in the following fiscal year. Additional activities are added during the fiscal year as necessary to accomplish programmatic goals. This report summarizes the activities and accomplishments of the NLLWMP during Fiscal Year 1996.

  11. Lysosomal pH Plays a Key Role in Regulation of mTOR Activity in Osteoclasts.

    PubMed

    Hu, Yingwei; Carraro-Lacroix, Luciene R; Wang, Andrew; Owen, Celeste; Bajenova, Elena; Corey, Paul N; Brumell, John H; Voronov, Irina

    2016-02-01

    Mammalian target of rapamycin (mTOR) is a serine/threonine kinase involved in the regulation of cell growth. It has been shown to play an important role in osteoclast differentiation, particularly at the earlier stages of osteoclastogenesis. mTOR activation and function, as part of mTORC1 complex, is dependent on lysosomal localization and the vacuolar H(+) -ATPase (V-ATPase) activity; however, the precise mechanism is still not well understood. Using primary mouse osteoclasts that are known to have higher lysosomal pH due to R740S mutation in the V-ATPase a3 subunit, we investigated the role of lysosomal pH in mTORC1 signaling. Our results demonstrated that +/R740S cells had increased basal mTOR protein levels and mTORC1 activity compared to +/+ osteoclasts, while mTOR gene expression was decreased. Treatment with lysosomal inhibitors chloroquine and ammonium chloride, compounds known to raise lysosomal pH, significantly increased mTOR protein levels in +/+ cells, confirming the importance of lysosomal pH in mTOR signaling. These results also suggested that mTOR could be degraded in the lysosome. To test this hypothesis, we cultured osteoclasts with chloroquine or proteasomal inhibitor MG132. Both chloroquine and MG132 increased mTOR and p-mTOR protein levels in +/+ osteoclasts, suggesting that mTOR undergoes both lysosomal and proteasomal degradation. Treatment with cycloheximide, an inhibitor of new protein synthesis, confirmed that mTOR is constitutively expressed and degraded. These results show that, in osteoclasts, the lysosome plays a key role not only in mTOR activation but also in its deactivation through protein degradation, representing a novel molecular mechanism of mTOR regulation.

  12. 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. PMID:26518482

  13. 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

  14. 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.

  15. Physical activity across the curriculum: year one process evaluation results

    PubMed Central

    Gibson, Cheryl A; Smith, Bryan K; DuBose, Katrina D; Greene, J Leon; Bailey, Bruce W; Williams, Shannon L; Ryan, Joseph J; Schmelzle, Kristin H; Washburn, Richard A; Sullivan, Debra K; Mayo, Matthew S; Donnelly, Joseph E

    2008-01-01

    Background Physical Activity Across the Curriculum (PAAC) is a 3-year elementary school-based intervention to determine if increased amounts of moderate intensity physical activity performed in the classroom will diminish gains in body mass index (BMI). It is a cluster-randomized, controlled trial, involving 4905 children (2505 intervention, 2400 control). Methods We collected both qualitative and quantitative process evaluation data from 24 schools (14 intervention and 10 control), which included tracking teacher training issues, challenges and barriers to effective implementation of PAAC lessons, initial and continual use of program specified activities, and potential competing factors, which might contaminate or lessen program effects. Results Overall teacher attendance at training sessions showed exceptional reach. Teachers incorporated active lessons on most days, resulting in significantly greater student physical activity levels compared to controls (p < 0.0001). Enjoyment ratings for classroom-based lessons were also higher for intervention students. Competing factors, which might influence program results, were not carried out at intervention or control schools or were judged to be minimal. Conclusion In the first year of the PAAC intervention, process evaluation results were instrumental in identifying successes and challenges faced by teachers when trying to modify existing academic lessons to incorporate physical activity. PMID:18606013

  16. Physical Activity in Childhood May Be the Key to Optimizing Lifespan Skeletal Health

    PubMed Central

    Gunter, Katherine B.; Almstedt, Hawley C.; Janz, Kathleen F

    2011-01-01

    Physical activities undertaken in childhood, particularly activities which apply large forces quickly convey optimal benefits to bone mass, size, and structure. Evidence is accumulating that benefits persist well beyond activity cessation. This review examines the potential for early childhood activity to improve bone mineralization and structure and explores childhood activity as prevention for osteoporosis in later life. PMID:21918458

  17. 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.

  18. 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

  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. O+OH-->O(2)+H: A key reaction for interstellar chemistry. New theoretical results and comparison with experiment.

    PubMed

    Lique, F; Jorfi, M; Honvault, P; Halvick, P; Lin, S Y; Guo, H; Xie, D Q; Dagdigian, P J; Kłos, J; Alexander, M H

    2009-12-14

    We report extensive, fully quantum, time-independent (TID) calculations of cross sections at low collision energies and rate constants at low temperatures for the O+OH reaction, of key importance in the production of molecular oxygen in cold, dark, interstellar clouds and in the chemistry of the Earth's atmosphere. Our calculations are compared with TID calculations within the J-shifting approximation, with wave-packet calculations, and with quasiclassical trajectory calculations. The fully quantum TID calculations yield rate constants higher than those from the more approximate methods and are qualitatively consistent with a low-temperature extrapolation of earlier experimental values but not with the most recent experiments at the lowest temperatures.

  1. Neuronal transmembrane chloride electrochemical gradient: a key player in GABA A receptor activation physiological effect.

    PubMed

    Cupello, A

    2003-06-01

    It has long been accepted that GABA is the main inhibitory neurotransmitter in the mammalian brain, acting via GABA(A) or GABA(B) receptors. However, new evidences have shown that it may work as an excitatory transmitter, especially in the brain of newly-born animals and acting via GABA(A) receptors. The difference in the end results of GABA(A) receptors activation in the two cases is not due to the receptor associated channels, which in both cases are chloride channels. The different physiological effect in the two cases is due to different electrochemical gradients for chloride. When GABA acting via GABA(A) receptors is inhibitory, either there is no transmembrane electrochemical gradient for chloride or there is one forcing such negative ions into the nerve cell, once chloride channels are open. Viceversa, GABA is excitatory when the electrochemical gradient is such to make chloride ions flow outside the cell, upon opening of the GABA activated chloride channels.In this review this concept is discussed in details and evidence in the scientific literature for the existence of different types of chloride pumps (either internalizing or extruding chloride) is compiled.

  2. Key amino acids of arabidopsis VKOR in the activity of phylloquinone reduction and disulfide bond formation.

    PubMed

    Yang, Xiao-Jian; Cui, Hao-Ran; Yu, Zhi-Bo; Du, Jia-Jia; Xu, Jia-Ning; Wang, Xiao-Yun

    2015-01-01

    Many proteins in chloroplast are regulated through the disulfide bond/thiol transformation to realize their activities. A homologue of VKOR (Vitamin K epoxide reductase) in Arabidopsis chloroplast is found to catalyze the disulfide bond formation in vivo and to mediate the specific phylloquinone reduction in vitro. It is also called LTO1 (Lumen Thiol Oxidoreductase 1). Investigations about functions and essential amino acid residues of AtVKOR have important theoretical significance to clarify the chloroplast redox regulation mechanism. In this study, several amino acids in the VKOR domain of AtVKOR were identified to be involved in binding of phylloquinone. Site-directed mutagenesis was used to study the function of these positions. The results suggested that residues Ser77, Leu87, Phe137 and Leu141 were quite important in the binding and catalyzing the reduction of phylloquinone. These residues were also involved in the electron transferring and disulfide bond formation of substrate proteins by motility assays in vivo, suggesting that the binding of phylloquinone not only affected the delivery of electrons to phylloquinone but also affected the whole electron transfer process. The conserved cysteines in the AtVKOR domain also played critical roles in phylloquinone reduction. When each of the four conserved cysteines was mutated to alanine, the mutants lost reduction activity entirely, suggesting that the four conserved cysteines played crucial roles in the electron transfer process. PMID:25267254

  3. Avoidance and activation as keys to depression: adaptation of the Behavioral Activation for Depression Scale in a Spanish sample.

    PubMed

    Barraca, Jorge; Pérez-Alvarez, Marino; Lozano Bleda, José Héctor

    2011-11-01

    In this paper we present the adaptation of the Behavioral Activation for Depression Scale (BADS), developed by Kanter, Mulick, Busch, Berlin, and Martell (2007), in a Spanish sample. The psychometric properties were tested in a sample of 263 participants (124 clinical and 139 non-clinical). The results show that, just as in the original English version, the Spanish BADS is a valid and internally consistent scale. Construct validity was examined by correlation with the BDI-II, AAQ, ATQ, MCQ-30, STAI and EROS. Factor analysis justified the four-dimensions of the original instrument (Activation, Avoidance/Rumination, Work/School Impairment and Social Impairment), although with some differences in the factor loadings of the items. Further considerations about the usefulness of the BADS in the clinical treatment of depressed patients are also suggested.

  4. A Unique Combination of Nutritionally Active Ingredients Can Prevent Several Key Processes Associated with Atherosclerosis In Vitro

    PubMed Central

    Moss, Joe W. E.; Davies, Thomas S.; Garaiova, Iveta; Plummer, Sue F.; Michael, Daryn R.; Ramji, Dipak P.

    2016-01-01

    Introduction Atherosclerosis is the underlying cause of cardiovascular disease that leads to more global mortalities each year than any other ailment. Consumption of active food ingredients such as phytosterols, omega-3 polyunsaturated fatty acids and flavanols are known to impart beneficial effects on cardiovascular disease although the combined actions of such agents in atherosclerosis is poorly understood. The aim of this study was to screen a nutritional supplement containing each of these active components for its anti-atherosclerotic effect on macrophages in vitro. Results The supplement attenuated the expression of intercellular adhesion molecule-1 and macrophage chemoattractant protein-1 in human and murine macrophages at physiologically relevant doses. The migratory capacity of human monocytes was also hindered, possibly mediated by eicosapentaenoic acid and catechin, while the ability of foam cells to efflux cholesterol was improved. The polarisation of murine macrophages towards a pro-inflammatory phenotype was also attenuated by the supplement. Conclusion The formulation was able to hinder multiple key steps of atherosclerosis development in vitro by inhibiting monocyte recruitment, foam cell formation and macrophage polarisation towards an inflammatory phenotype. This is the first time a combination these ingredients has been shown to elicit such effects and supports its further study in preclinical in vivo models. PMID:26950833

  5. 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.

  6. 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…

  7. 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

  8. 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.

  9. 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.

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. An Activity-Based Learning Approach for Key Geographical Information Systems (GIS) Concepts

    ERIC Educational Resources Information Center

    Srivastava, Sanjeev Kumar; Tait, Cynthia

    2012-01-01

    This study presents the effect of active learning methods of concepts in geographical information systems where students participated in a series of interlocked learning experiences. These activities spanned several teaching weeks and involved the creation of a hand drawn map that was scanned and geo-referenced with locations' coordinates derived…

  15. 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…

  16. Synthesis and quorum sensing inhibitory activity of key phenolic compounds of ginger and their derivatives.

    PubMed

    Kumar, N Vijendra; Murthy, Pushpa S; Manjunatha, J R; Bettadaiah, B K

    2014-09-15

    Phenolic components of ginger (Zingiber officinale Roscoe) viz. [6]-gingerol, [6]-shogaol and zingerone exhibited quorum sensing inhibitory activity (QSI) against Chromobacterium violaceum and Pseudomonas aeruginosa. The inhibitory activity of all the compounds was studied by zone inhibition, pyocyanin, and violacein assay. All the compounds displayed good inhibition at 500ppm. [6]-Azashogaol, a new derivative of [6]-shogaol has been synthesized by Beckmann rearrangement of its oxime in the presence of ZnCl2. The structure elucidation of this new derivative was carried out by 1D ((1)H NMR and (13)C NMR) and 2D-NMR (COSY, HSQC and NOESY) spectral studies. This compound showed good QSI activity against P. aeruginosa. An isoxazoline derivative of [6]-gingerol was prepared and it exhibited good QSI activity. Present study illustrated that, the phenolic compounds of ginger and their derivatives form a class of compounds with promising QSI activity. PMID:24767081

  17. 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. PMID:25775592

  18. 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.

  19. KEY COMPARISON: Final report on CCEM key comparison CCEM.RF-K10.CL (GT-RF/99-2) 'Power in 50 Ω coaxial lines, frequency: 50 MHz to 26 GHz' measurement techniques and results

    NASA Astrophysics Data System (ADS)

    Janik, Dieter; Inoue, T.; Michaud, A.

    2006-01-01

    This report summarizes the results and the measuring methods of an international key comparison between twelve national metrology institutes (NMIs) and is concerning the calibration factor of RF power sensors in the coaxial 3.5 mm line for frequencies up to 26 GHz. Two RF power travelling standards fitted with male PC 3.5 mm connectors were measured at seven frequencies. The following NMIs participated: NMIJ (Japan), NRC (Canada), NIST (USA), METAS (Switzerland), CSIR-NML (South Africa), NMIA (Australia), NPL (UK), SiQ (Slovenia), IEN (Italy), VNIIFTRI (Russian Federation), SPRING (Singapore) and PTB (Germany), as the pilot laboratory. 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 CCEM, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

  20. Monitoring the Future: National Results on Adolescent Drug Use. Overview of Key Findings 2005. NIH Publication No. 06-5882

    ERIC Educational Resources Information Center

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

    2006-01-01

    Results from the Monitoring the Future's 2005 nationwide survey of 8th, 10th, and 12th grade students are given in this report. Recent trends in the use of licit and illicit drugs are emphasized, as well as trends in the levels of perceived risk and personal disapproval associated with each drug. This study has shown these beliefs and attitudes to…

  1. Transcriptomic Analysis of Musca domestica to Reveal Key Genes of the Prophenoloxidase-Activating System.

    PubMed

    Li, Dianxiang; Liang, Yongli; Wang, Xianwei; Wang, Lei; Qi, Mei; Yu, Yang; Luan, Yuanyuan

    2015-09-01

    The proPO system regulates melanization in arthropods. However, the genes that are involved in the proPO system in housefly Musca domestica remain unclear. Thus, this study analyzed the combined transcriptome obtained from M. domestica larvae, pupae, and adults that were either normal or bacteria-challenged by an Escherichia coli and Staphylococcus aureus mixture. A total of 54,821,138 clean reads (4.93 Gb) were yielded by Illumina sequencing, which were de novo assembled into 89,842 unigenes. Of the 89,842 unigenes, based on a similarity search with known genes in other insects, 24 putative genes related to the proPO system were identified. Eight of the identified genes encoded for peptidoglycan recognition receptors, two encoded for prophenoloxidases, three encoded for prophenoloxidase-activating enzymes, and 11 encoded for serine proteinase inhibitors. The expression levels of these identified genes were investigated by qRT-PCR assay, which were consistent with expected activation process of the proPO system, and their activation functions were confirmed by the measurement of phenoloxidase activity in bacteria-infected larvae after proPO antibody blockage, suggesting these candidate genes might have potentially different roles in the activation of proPO system. Collectively, this study has provided the comprehensive transcriptomic data of an insect and some fundamental basis toward achieving understanding of the activation mechanisms and immune functions of the proPO system in M. domestica.

  2. Transcriptomic Analysis of Musca domestica to Reveal Key Genes of the Prophenoloxidase-Activating System

    PubMed Central

    Li, Dianxiang; Liang, Yongli; Wang, Xianwei; Wang, Lei; Qi, Mei; Yu, Yang; Luan, Yuanyuan

    2015-01-01

    The proPO system regulates melanization in arthropods. However, the genes that are involved in the proPO system in housefly Musca domestica remain unclear. Thus, this study analyzed the combined transcriptome obtained from M. domestica larvae, pupae, and adults that were either normal or bacteria-challenged by an Escherichia coli and Staphylococcus aureus mixture. A total of 54,821,138 clean reads (4.93 Gb) were yielded by Illumina sequencing, which were de novo assembled into 89,842 unigenes. Of the 89,842 unigenes, based on a similarity search with known genes in other insects, 24 putative genes related to the proPO system were identified. Eight of the identified genes encoded for peptidoglycan recognition receptors, two encoded for prophenoloxidases, three encoded for prophenoloxidase-activating enzymes, and 11 encoded for serine proteinase inhibitors. The expression levels of these identified genes were investigated by qRT-PCR assay, which were consistent with expected activation process of the proPO system, and their activation functions were confirmed by the measurement of phenoloxidase activity in bacteria-infected larvae after proPO antibody blockage, suggesting these candidate genes might have potentially different roles in the activation of proPO system. Collectively, this study has provided the comprehensive transcriptomic data of an insect and some fundamental basis toward achieving understanding of the activation mechanisms and immune functions of the proPO system in M. domestica. PMID:26156588

  3. 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

    2015-04-01

    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.

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

    NASA Astrophysics Data System (ADS)

    Montgomery, Edward E.

    2010-05-01

    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.

  5. 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.

  6. Surface Snowpack Key to Bromine Activation in a Changing Arctic Environment

    NASA Astrophysics Data System (ADS)

    Pratt, Kerri; Custard, Kyle; Shepson, Paul; Douglas, Thomas; Pöhler, Denis; Stephan, General; Zielcke, Johannes; Simpson, William; Platt, Ulrich; von Glasow, Roland; Tanner, David; Huey, L. Gregory; Carlsen, Mark; Stirm, Brian

    2013-04-01

    Arctic sea ice is rapidly declining and transforming from a multiyear ice pack to thinner, more saline, seasonal ice, which has important implications for Arctic atmospheric composition. Following springtime polar sunrise, "ozone depletion events", attributed to bromine chemistry, lead to episodic decreases in lower tropospheric ozone concentrations to near zero, concurrent with mercury depletion and deposition. Despite our increasing understanding of the spatial variability of BrO and possible reaction pathways based on laboratory studies, important questions remain regarding the most efficient sources of and mechanisms for Arctic halogen activation. During the March-April 2012 BRomine, Ozone, and Mercury EXperiment (BROMEX) in Barrow, Alaska, outdoor chamber experiments with snow and ice samples were conducted. Ozone was added as the precursor oxidant, and the samples were investigated with and without ambient sunlight. Samples included first-year sea ice, brine icicles, several layers of snow above first-year sea ice, and seasonal snow above the tundra. Chemical ionization mass spectrometry was utilized to monitor Br2 production. Tundra snow and surface snow above sea ice produced the most Br2, with no production resulting from sea ice and basal snow directly above sea ice. Overall, the most efficient Br2 production was observed from snow samples characterized by lower pH and higher bromide/chloride ratios. Br2 was only observed in the presence of sunlight, indicating the role of snowpack photochemical reactions and the hydroxyl radical in its production. Br2 production via the surface snowpack explains previously-observed BrO enhancements above sea ice, as well as observations of inland tundra hotspots in measured BrO by aircraft-based nadir MAX-DOAS (Multi Axis-Differential Optical Absorption Spectroscopy) measurements, conducted during BROMEX. The findings indicate that atmospherically processed snow is likely a major source of Arctic bromine release, which

  7. 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.

  8. 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.

  9. 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.

  10. Summary of the Results of STIS SMOV4 Calibration Activities

    NASA Astrophysics Data System (ADS)

    Proffitt, Charles R.; Aloisi, Alessandra; Bohlin, Ralph; Cox, Colin, Goudfrooij, Paul; Gull, Thodore, R.; Kaiser, Mary Beth; Lallo, Matt; Lennon, Daniel J.; Lindler, Don J.; Makidon, Russ; Niemi, Sami-Matias; Serrano, Beverly; Wheeler, Thomas; Wolfe, Michael E.; Serrano, Beverly; Woodgate, Bruce; Zheng, Wei

    2014-01-01

    After HST Servicing Mission 4 (SM4), there was a period of Science Mission Observatory Verification (SMOV4), to check out the new and repaired instruments. Here we summarize the execution and results of the Space Telescope Imaging Spectrograph (STIS) SMOV 4 activities undertaken to ensure that the repaired STIS instrument was ready to carry out its scheduled science program after a nearly five year hiatus in operation. The results of the initial aliveness and functional tests are reviewed, anomalies that aff ected the execution of the STIS SMOV plan are discussed, and the results of each STIS SMOV activity executed are summarized. In most respects the performance of STIS after the SM4 repair is very similar to that seen prior to the 2004 failure. Notable chang es include a significant and unexpected enhancement of the NUV MAMA dark rate that has been declining only very slowly, and continued degradation of the CCD performance due to radiation damage. Post - repair throughputs of most modes are close to expectation s based on extrapolation of previous trends.

  11. Complement activation plays a key role in the side-effects of rituximab treatment.

    PubMed

    van der Kolk, L E; Grillo-López, A J; Baars, J W; Hack, C E; van Oers, M H

    2001-12-01

    Treatment with rituximab, a chimaeric anti-CD20 monoclonal antibody, can be associated with moderate to severe first-dose side-effects, notably in patients with high numbers of circulating tumour cells. The aim of this study was to elucidate the mechanism of these side-effects. At multiple early time points during the first infusion of rituximab, complement activation products (C3b/c and C4b/c) and cytokines [tumour necrosis factor alpha (TNF-alpha), interleukin 6 (IL-6) and IL-8] were measured in five relapsed low-grade non-Hodgkin's lymphoma (NHL) patients. Infusion of rituximab induced rapid complement activation, preceding the release of TNF-alpha, IL-6 and IL-8. Although the study group was small, the level of complement activation appeared to be correlated both with the number of circulating B cells prior to the infusion (r = 0.85; P = 0.07) and with the severity of the side-effects. We conclude that complement plays a pivotal role in the pathogenesis of side-effects of rituximab treatment. As complement activation can not be prevented by corticosteroids, it might be relevant to study the possible role of complement inhibitors during the first administration of rituximab.

  12. 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.

  13. 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…

  14. 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…

  15. 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…

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

    PubMed

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

    2012-02-01

    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

  17. 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

  18. 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...

  19. Instrumenting Mathematical Activity: Reflections on Key Studies of the Educational Use of Computer Algebra Systems.

    ERIC Educational Resources Information Center

    Ruthven, Kenneth

    2002-01-01

    Examines the process through which students learn to make functional use of computer algebra systems (CAS) and the interaction between that process and the wider mathematical development of students. Highlights important challenges that arise in instrumenting classroom mathematical activity and instrumentalizing CAS correspondingly. Reveals…

  20. 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

  1. 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.

  2. Is Nox4 a key regulator of the activated state of fibroblasts in systemic sclerosis?

    PubMed

    Böhm, Markus; Dosoki, Heba; Kerkhoff, Claus

    2014-09-01

    The family of nicotinamide adenine dinucleotide phosphate (NADPH) oxidases consists of phagocytic gp91(phox) and six-related isoforms. Recent evidence indicates that the NADPH oxidase isoform Nox4 controls vascular, renal and pulmonary injury. We propose that Nox4 is an intrinsic regulator of the activated state of dermal fibroblasts in systemic sclerosis (SSc). Profibrotic cytokines on the one hand and antifibrogenic factors such as α-melanocyte-stimulating hormone on the other hand may target Nox4 as an intracellular nodal point. Via increased or decreased generation of reactive oxygen species and/or hydrogen peroxide, Nox4 could orchestrate collagen synthesis, differentiation of dermal fibroblasts into a profibrotic myofibroblast phenotype and thus dermal fibrosis. Confirmation of this hypothesis will have important consequences in our understanding of the activated state of dermal fibroblasts in SSc. Based on the availability of clinically useful Nox4 inhibitors, novel antifibrotic therapies of SSc can be envisioned. PMID:25040787

  3. Effect of feed starvation on side-stream anammox activity and key microbial populations.

    PubMed

    Reeve, Petra J; Mouilleron, Irina; Chuang, Hui-Ping; Thwaites, Ben; Hyde, Kylie; Dinesh, Nirmala; Krampe, Joerg; Lin, Tsair-Fuh; van den Akker, Ben

    2016-04-15

    The anaerobic ammonium oxidation (anammox) process is widely acknowledged to be susceptible to a wide range of environmental factors given the slow growth rate of the anammox bacteria. Surprisingly there is limited experimental data regarding the susceptibility of the anammox process to feed starvations which may be encountered in full-scale applications. Therefore, a study was established to investigate the impact of feed starvations on nitritation and anammox activity in a demonstration-scale sequencing batch reactor. Three starvation periods were trialled, lasting one fortnight (15 d), one month (33 d) and two months (62 d). Regardless of the duration of the starvation period, assessment of the ammonia removal performance demonstrated nitritation and anammox activity were reinstated within one day of recovery operation. Characterisation of the community structure using 16S rRNA and functional genes specific for nitrogen-related microbes showed there was no clear impact or shift in the microbial populations between starvation and recovery phases. PMID:26861222

  4. [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.

  5. [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. PMID:23726832

  6. 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.

  7. Novel ureas and thioureas of 15-membered azalides with antibacterial activity against key respiratory pathogens.

    PubMed

    Bukvić Krajacić, Mirjana; Novak, Predrag; Dumić, Miljenko; Cindrić, Mario; Paljetak, Hana Cipcić; Kujundzić, Nedjeljko

    2009-09-01

    The new ureas and thioureas of 15-membered azalides, N''-substituted 9a-(N'-carbamoyl-gamma-aminopropyl) (4), 9a-(N'-thiocarbamoyl-gamma-aminopropyl) (6), 9a-[N'-(beta-cyanoethyl)-N'-(carbamoyl-gamma-aminopropyl)] (8) and 9a-[N'-(beta-cyanoethyl)-N'-(thiocarbamoyl-gamma-aminopropyl)] (10) of 9-deoxo-9-dihydro-9a-aza-9a-homoerythromycin A (2), were synthesized and structurally characterized by NMR and IR spectroscopic methods and mass spectrometry. The new compounds were evaluated in vitro against a panel of erythromycin susceptible and erythromycin-resistant gram-positive and gram-negative bacterial strains. These compounds displayed an excellent overall antibacterial in vitro activity against erythromycin sensitive gram-positive strains, Streptococcus pneumoniae, Streptococcus pyogenes, Staphylococcus aureus, and good against negative strains, Moraxella catarrhalis and Haemophilus influenzae. In addition, several ureas with naphthyl substituents (4f, 4g, 4h) showed better activity in comparison to azithromycin against inducible resistant S. pyogenes. Ureas with naphthyl substituents 4g, 4h and thiourea 8h displayed moderate activity against constitutively resistant S. pneumoniae.

  8. [CREB activation is a key player for ischemic tolerance in the brain].

    PubMed

    Kitagawa, Kazuo; Sasaki, Tsutomu; Terasaki, Yasukazu; Yagita, Yoshiki; Mochizuki, Hideki

    2012-01-01

    Ischemic tolerance is as powerful and reproducible for neuro-protection as hypothermia. Several pathways could be involved in acquisition of ischemic tolerance. CREB is an abundant transcription factor in the brain and plays critical role on synaptic plasticity and neuronal survival. CREB activation has been also shown to be involved in ischemic tolerance. Ischemia or oxygen-glucose deprivation leads to release of glutamate, which binds to synaptic NMDA receptor. Then, influx of calcium ions into intracellular space activates calcium-calmodulin dependent protein kinase (CaMK). CaMK I/IV phosphorylates Ser 133 of CREB, and Thr 484 of salt-inducible kinase (SIK). Phosphorylation of SIK2 at Thr 484 triggers degradation of SIK2 through ubiquitin proteasome system. SIK2 maintains the phosphorylation level of CREB-regulated transcriptional co-activator (CRTC). Degradation of SIK2 induces dephosphorylation of CRTC1, and moves CRTC1 from cytoplasm into nucleus. Thus CRTC1 binds to basic ZIP domain of CREB. Both Ser133 phosphorylation and CRTC1 bound to the basic ZIP domain of CREB enhances CRE-mediated transcription, induces gene expression of survival factors, and renders the neurons resistant to subsequent severe ischemia.

  9. 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

  10. Paleoseismic investigations along a key active fault within the Gulf of Corinth, Greece

    NASA Astrophysics Data System (ADS)

    Koukouvelas, I. K.; Kokkalas, S.; Xypolias, P.

    2008-07-01

    The study of paleoseismological and archaeological excavations provide clues for the evolution of Helike Fault, located along the westernmost end of the Gulf of Corinth, that displays high activity and exerts control on the landscape. In this study we present evidence from paleoseismic trenches which revealed well defined fault strands and clear colluvial stratigraphy. We focus on the two main segments of the Helike Fault and their implications on strong earthquake activity. The Helike Fault is a major tectonic structure that influenced the evolution of ancient settlements on the Helike Delta, from the Early Bronze Age through the Byzantine period, till present times. The eastern fault segment appears to control the southern Gulf morphology, while the western segment is controlling the large Aigion basin. Interbedded organic-rich soils and gravels dominate in all trenches. Fault strands that control successive scarp-derived colluvial deposits were identified within the trenches and indicate the continuous seismic activity along the fault trace. Co-seismic offsets, open cracks filled with debris and liquefaction related deformation was also recognized. At least seven seismic events were identified inside the excavated trenches, during the last 10 ka. The estimated vertical throw along the fault segments, observed within the trenches, is on the order of 1 meter per event. Based on dating of colluvial wedges we estimated the Holocene slip rate on the Helike Fault, which shows an increase from ~0.3 mm/yr to 2 mm/yr in the last 2 ka. We consider the derived slip rates to be minimum values due to the implication of erosional effects and sediment accumulation from the upthrown block. The Helike fault appears to play a crucial role both in subsidence of the Helike delta plain and in shifting Kerynites river course that runs between the two Helike fault segments. The Helike Fault activity and the clustering of surface rupturing events on the Helike fault seems to fit well

  11. 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.

  12. Surface facet of palladium nanocrystals: a key parameter to the activation of molecular oxygen for organic catalysis and cancer treatment.

    PubMed

    Long, Ran; Mao, Keke; Ye, Xiaodong; Yan, Wensheng; Huang, Yaobing; Wang, Jianyong; Fu, Yao; Wang, Xisheng; Wu, Xiaojun; Xie, Yi; Xiong, Yujie

    2013-02-27

    In many organic reactions, the O(2) activation process involves a key step where inert ground triplet O(2) is excited to produce highly reactive singlet O(2). It remains elusive what factor induces the change in the electron spin state of O(2) molecules, although it has been discovered that the presence of noble metal nanoparticles can promote the generation of singlet O(2). In this work, we first demonstrate that surface facet is a key parameter to modulate the O(2) activation process on metal nanocrystals, by employing single-facet Pd nanocrystals as a model system. The experimental measurements clearly show that singlet O(2) is preferentially formed on {100} facets. The simulations further elucidate that the chemisorption of O(2) to the {100} facets can induce a spin-flip process in the O(2) molecules, which is achieved via electron transfer from Pd surface to O(2). With the capability of tuning O(2) activation, we have been able to further implement the {100}-faceted nanocubes in glucose oxidation. It is anticipated that this study will open a door to designing noble metal nanocatalysts for O(2) activation and organic oxidation. Another perspective of this work would be the controllability in tailoring the cancer treatment materials for high (1)O(2) production efficiency, based on the facet control of metal nanocrystals. In the cases of both organic oxidation and cancer treatment, it has been exclusively proven that the efficiency of producing singlet O(2) holds the key to the performance of Pd nanocrystals in the applications.

  13. 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

  14. Test results of an active magnetic regenerative refrigerator

    NASA Astrophysics Data System (ADS)

    Degregoria, A. J.; Feuling, L. J.; Laatsch, J. F.; Rowe, J. R.; Trueblood, J. R.; Wang, A. A.

    The principle of the Active Magnetic Regenerator (AMR) is tested with an experimental refrigerator designed to operate within the temperature range of about 4 to 80 K. Applications, including helium and hydrogen liquefaction and hydrogen slush generation, are envisioned. The device uses a single moveable superconducting solenoidal magnet in persistent mode to alternately charge and discharge two in-line beds of magnetic material. Between magnet motions, a double-acting piston displacer moves heat transfer fluid in the form of helium gas through the beds, absorbing heat at the cold heat exchanger and rejecting heat at the hot heat exchanger. A description of the refrigerator and performance results are presented. Comparisons to a detailed AMR model are shown.

  15. 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.

  16. 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. PMID:22555950

  17. 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.

  18. Key active site residues in the inhibition of acetylcholinesterases by soman.

    PubMed

    Qian, N; Kovach, I M

    1993-12-27

    Molecular modeling (GEMM 7.3) and molecular mechanics calculations (YETI V 5.3) using the X-ray coordinates for acetylcholinesterase (AChE) from Torpedo californica indicate electrostatic stabilization by the active site, Glu-199, of the developing positive charge on the incipient carbonium ion in the dealkylation in the adducts of AChE with PSCR and PSCS diastereomers of 2-(3,3-dimethylbutyl) methylphosphonofluoridate (soman). His-440 is indispensable as a general acid catalyst of C-O bond breaking in the dealkylation reaction and that of bond breaking to the Ser gamma-O in reactivation. This demand for catalysis seems to be satisfied for the reactivation of enzyme from the PSCS diastereomer of soman, but not from the P(S)C(R) diastereomer.

  19. 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.

  20. Is active management the key to the conservation of saproxylic biodiversity? Pollarding promotes the formation of tree hollows.

    PubMed

    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

  1. Activation of Benznidazole by Trypanosomal Type I Nitroreductases Results in Glyoxal Formation

    PubMed Central

    Hall, Belinda S.

    2012-01-01

    Benznidazole, a 2-nitroimidazole, is the front-line treatment used against American trypanosomiasis, a parasitic infection caused by Trypanosoma cruzi. Despite nearly 40 years of use, the trypanocidal activity of this prodrug is not fully understood. It has been proposed that benznidazole activation leads to the formation of reductive metabolites that can cause a series of deleterious effects, including DNA damage and thiol depletion. Here, we show that the key step in benznidazole activation involves an NADH-dependent trypanosomal type I nitroreductase. This catalyzes an oxygen-insensitive reaction with the interaction of enzyme, reductant, and prodrug occurring through a ping-pong mechanism. Liquid chromatography/mass spectrometry (LC/MS) analysis of the resultant metabolites identified 4,5-dihydro-4,5-dihydroxyimidazole as the major product of a reductive pathway proceeding through hydroxylamine and hydroxy intermediates. The breakdown of this product released the reactive dialdehyde glyoxal, which, in the presence of guanosine, generated guanosine-glyoxal adducts. These experiments indicate that the reduction of benznidazole by type I nitroreductase activity leads to the formation of highly reactive metabolites and that the expression of this enzyme is key to the trypanocidal properties displayed by the prodrug. PMID:22037852

  2. PP2A inhibition results in hepatic insulin resistance despite Akt2 activation.

    PubMed

    Galbo, Thomas; Perry, Rachel J; Nishimura, Erica; Samuel, Varman T; Quistorff, Bjørn; Shulman, Gerald I

    2013-10-01

    In the liver, insulin suppresses hepatic gluconeogenesis by activating Akt, which inactivates the key gluconeogenic transcription factor FoxO1 (Forkhead Box O1). Recent studies have implicated hyperactivity of the Akt phosphatase Protein Phosphatase 2A (PP2A) and impaired Akt signaling as a molecular defect underlying insulin resistance. We therefore hypothesized that PP2A inhibition would enhance insulin-stimulated Akt activity and decrease glucose production. PP2A inhibitors increased hepatic Akt phosphorylation and inhibited FoxO1in vitro and in vivo, and suppressed gluconeogenesis in hepatocytes. Paradoxically, PP2A inhibition exacerbated insulin resistance in vivo. This was explained by phosphorylation of both hepatic glycogen synthase (GS) (inactivation) and phosphorylase (activation) resulting in impairment of glycogen storage. Our findings underline the significance of GS and Phosphorylase as hepatic PP2A substrates and importance of glycogen metabolism in acute plasma glucose regulation. PMID:24150286

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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.

  8. 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

  9. 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

  10. 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

  11. 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

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

    PubMed

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

    2015-12-01

    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

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

    PubMed

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

    2015-12-01

    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

  14. (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.

  15. Solar activity variations of ionosonde measurements and modeling results

    NASA Astrophysics Data System (ADS)

    Altadill, D.; Arrazola, D.; Blanch, E.; Buresova, D.

    2008-08-01

    The time series of hourly electron density profiles N(h) obtained at several mid-latitude stations in Europe have been used to obtain N(h) profiles on a monthly basis and to extract both the expected bottomside parameters and a proxy of the ionospheric variability as functions of time and height. With these data we present advances on a “Local Model” technique for the parameters B0 and B1, its applicability to other ionospheric stations, to other bottomside ionospheric parameters, and to modeling the time/height variability of the profile. The Local Model (LM) is an empirical model based on the experimental results of the solar activity dependence of the daily and seasonal behavior of the above parameters. The LM improves the IRI-2001 prediction of the B0 and B1 by factor of two at mid-latitudes. Moreover, the LM can be used to simulate other ionospheric parameters and to build mean N(h) profiles and the deviations from them. The modeling of both the average N(h) profiles and their deviations is an useful tool for ionospheric model users who want to know both the expected patterns and their deviations.

  16. New approaches to enhance active steering system functionalities: preliminary results

    NASA Astrophysics Data System (ADS)

    Serarslan, Benan

    2014-09-01

    An important development of the steering systems in general is active steering systems like active front steering and steer-by-wire systems. In this paper the current functional possibilities in application of active steering systems are explored. A new approach and additional functionalities are presented that can be implemented to the active steering systems without additional hardware such as new sensors and electronic control units. Commercial active steering systems are controlling the steering angle depending on the driving situation only. This paper introduce methods for enhancing active steering system functionalities depending not only on the driving situation but also vehicle parameters like vehicle mass, tyre and road condition. In this regard, adaptation of the steering ratio as a function of above mentioned vehicle parameters is presented with examples. With some selected vehicle parameter changes, the reduction of the undesired influences on vehicle dynamics of these parameter changes has been demonstrated theoretically with simulations and with real-time driving measurements.

  17. 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

  18. KEY COMPARISON: Measurement of activity concentration of radionuclide Cs-137 in a solution (COOMET Project no 386/RU/06)

    NASA Astrophysics Data System (ADS)

    Kharitonov, I. A.; Zanevsky, A. V.; Milevski, V.; Ivaniukovich, A.; Oropesa Verdecia, P.; Moreno León, Y.; Svec, A.

    2008-01-01

    A COOMET.RI(II)-K2.Cs-137 comparison of the measurement of a standardized solution of Cs-137 has enabled three national metrology institutes in the COOMET to demonstrate their traceability to the SI. The results of the comparison will be used to evaluate degrees of equivalence for these institutes through the measurements of the linking laboratory in the key comparison BIPM.RI(II)-K1.Cs-137. 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 Section II, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

  19. Post-anthesis alternate wetting and moderate soil drying enhances activities of key enzymes in sucrose-to-starch conversion in inferior spikelets of rice.

    PubMed

    Zhang, Hao; Li, Hongwei; Yuan, Liming; Wang, Zhiqin; Yang, Jianchang; Zhang, Jianhua

    2012-01-01

    This study tested the hypothesis that a post-anthesis moderate soil drying can improve grain filling through regulating the key enzymes in the sucrose-to-starch pathway in the grains of rice (Oryza sativa L.). Two rice cultivars were field grown and two irrigation regimes, alternate wetting and moderate soil drying (WMD) and conventional irrigation (CI, continuously flooded), were imposed during the grain-filling period. The grain-filling rate and activities of four key enzymes in sucrose-to-starch conversion, sucrose synthase (SuSase), adenosine diphosphate-glucose pyrophosphorylase (AGPase), starch synthase (StSase), and starch branching enzyme (SBE), showed no significant difference between WMD and CI regimes for the earlier flowering superior spikelets. However, they were significantly enhanced by the WMD for the later flowering inferior spikelets. The activities of both soluble and insoluble acid invertase in the grains were little affected by the WMD. The two cultivars showed the same tendencies. The activities of SuSase, AGPase, StSase, and SBE in grains were very significantly correlated with the grain-filling rate. The abscisic acid (ABA) concentration in inferior spikelets was remarkably increased in the WMD and very significantly correlated with activities of SuSase, AGPase, StSase, and SBE. Application of ABA on plants under CI produced similar results to those seen in plants receiving WMD. Applying fluridone, an indirect inhibitor of ABA synthesis, produced the opposite effect. The results suggest that post-anthesis WMD could enhance sink strength by regulating the key enzymes involved, and consequently, increase the grain-filling rate and grain weight of inferior spikelets. ABA plays an important role in this process.

  20. 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. PMID:25897087

  1. 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

  2. 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.

  3. Structural Dissection of the Active Site of Thermotoga maritima β-Galactosidase Identifies Key Residues for Transglycosylating Activity.

    PubMed

    Talens-Perales, David; Polaina, Julio; Marín-Navarro, Julia

    2016-04-13

    Glycoside hydrolases, specifically β-galactosidases, can be used to synthesize galacto-oligosaccharides (GOS) due to the transglycosylating (secondary) activity of these enzymes. Site-directed mutagenesis of a thermoresistant β-galactosidase from Thermotoga maritima has been carried out to study the structural basis of transgalactosylation and to obtain enzymatic variants with better performance for GOS biosynthesis. Rational design of mutations was based on homologous sequence analysis and structural modeling. Analysis of mutant enzymes indicated that residue W959, or an alternative aromatic residue at this position, is critical for the synthesis of β-3'-galactosyl-lactose, the major GOS obtained with the wild-type enzyme. Mutants W959A and W959C, but not W959F, showed an 80% reduced synthesis of this GOS. Other substitutions, N574S, N574A, and F571L, increased the synthesis of β-3'-galactosyl-lactose about 40%. Double mutants F571L/N574S and F571L/N574A showed an increase of about 2-fold.

  4. 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

  5. KEY COMPARISON: BIPM comparison BIPM.RI(II)-K1.Cu-64 of the activity measurements of the radionuclide 64Cu

    NASA Astrophysics Data System (ADS)

    Michotte, C.; Courte, S.; Ratel, G.; Kossert, K.; Nähle, O. J.

    2009-01-01

    In 2009, the Physikalisch-Technische Bundesanstalt (PTB), Germany, submitted a sample of known activity of 64Cu to the International Reference System (SIR) for activity comparison at the Bureau International des Poids et Mesures (BIPM). The value of the activity submitted was about 9.3 MBq. The result of this new comparison has been approved for publication by Section II of the Consultative Committee for Ionizing Radiation (CCRI(II)), comparison identifier BIPM.RI(II)-K1.Cu-64. 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 Section II, according to the provisions of the CIPM Mutual Recognition Arrangement (MRA).

  6. Activation of Hypoxia‐Inducible Factor‐2 in Adipocytes Results in Pathological Cardiac Hypertrophy

    PubMed Central

    Lin, Qun; Huang, Yan; Booth, Carmen J.; Haase, Volker H.; Johnson, Randall S.; Celeste Simon, M.; Giordano, Frank J.; Yun, Zhong

    2013-01-01

    Background Obesity can cause structural and functional abnormalities of the heart via complex but largely undefined mechanisms. Emerging evidence has shown that obesity results in reduced oxygen concentrations, or hypoxia, in adipose tissue. We hypothesized that the adipocyte hypoxia‐signaling pathway plays an essential role in the development of obesity‐associated cardiomyopathy. Methods and Results Using a mouse model in which the hypoxia‐inducible factor (HIF) pathway is activated by deletion of the von Hippel–Lindau gene specifically in adipocytes, we found that mice with adipocyte–von Hippel–Lindau deletion developed lethal cardiac hypertrophy. HIF activation in adipocytes results in overexpression of key cardiomyopathy‐associated genes in adipose tissue, increased serum levels of several proinflammatory cytokines including interleukin‐1β and monocyte chemotactic protein‐1, and activation of nuclear factor–κB and nuclear factor of activated T cells in the heart. Interestingly, genetic deletion of Hif2a, but not Hif1a, was able to rescue cardiac hypertrophy and abrogate adipose inflammation. Conclusion We have discovered a previously uncharacterized mechanism underlying a critical and direct role of the adipocyte HIF‐2 transcription factor in the development of adipose inflammation and pathological cardiac hypertrophy. PMID:24326162

  7. 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. PMID:26119225

  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. Soil Moisture Active Passive Satellite Status and Recent Validation Results

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The Soil Moisture Active Passive (SMAP) mission was launched in January, 2015 and began its calibration and validation (cal/val) phase in May, 2015. Cal/Val will begin with a focus on instrument measurements, brightness temperature and backscatter, and evolve to the geophysical products that include...

  10. Active commuting and physical activity in adolescents from Europe: results from the HELENA study.

    PubMed

    Chillón, Palma; Ortega, Francisco B; Ruiz, Jonatan R; De Bourdeaudhuij, Ilse; Martínez-Gómez, David; Vicente-Rodriguez, Germán; Widhalm, Kurt; Molnar, Dénes; Gottrand, Frédéric; González-Gross, Marcela; Ward, Dianne S; Moreno, Luis A; Castillo, Manuel J; Sjöström, Michael

    2011-05-01

    We assessed commuting patterns in adolescents from 10 European cities and examined associations with physical activity (PA). A total of 3112 adolescents were included. PA was objectively measured with accelerometry. Commuting patterns and overall PA were self-reported using questions from the International Physical Activity Questionnaire modified for adolescents (IPAQ-A). Adolescents reported to spend 30 min (15,60) [expressed as median (25th, 75th percentiles)] walking. In boys, associations between active commuting (walking and biking) and PA levels were observed for moderate, moderate-to-vigorous and overall PA. In girls, these associations were observed for moderate and moderate-to-vigorous PA (walking). Similar results were found with the IPAQ-A. We observed positive associations between overall commuting and PA levels in European adolescents, yet due to the cross-sectional study design we cannot state the direction of these. Future studies should address the causation between active commuting and PA levels.

  11. α-linolenic acid concentration and not wounding per se is the key regulator of octadecanoid (oxylipin) pathway activity in rice (Oryza sativa L.) leaves.

    PubMed

    Christeller, John T; Galis, Ivan

    2014-10-01

    Using an in vitro system composed of crushed leaf tissues to simulate the wounding response in rice leaves, we established that synthesis of jasmonic acid (JA) and jasmonic acid-isoleucine (JA-Ile) can only occur in unwounded tissue and, in wounded tissue, that only the chloroplast-located section of the octadecanoid pathway is active, resulting in the accumulation of 12-oxo-phytodienoic acid (OPDA). We further showed that OPDA accumulation in vitro was inhibited by 90% using the general lipase inhibitor, tetrahydrolipstatin, indicating that production of α-linolenic acid was the rate-limiting step in octadecanoid pathway activity in rice following wounding and the enzyme capacity for an active pathway was already present. We confirmed this result by showing that added α-linolenic acid stimulated OPDA synthesis in vitro and stimulated OPDA, JA and JA-Ile synthesis in vivo in unwounded tissue. Thus, the response to wounding can be mimicked by the provision of free α-linolenic acid. Our results draw attention to the key importance of lipase activity in initiation of JA and JA-Ile biosynthesis and our lack of knowledge of the cognate lipase(s), lipase substrate identity and mechanism(s) of activation in wounded and unwounded tissue.

  12. 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

  13. 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.

  14. 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

  15. 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. PMID:23615061

  16. 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.

  17. Active X-ray mirror development at UCL: preliminary results

    NASA Astrophysics Data System (ADS)

    Atkins, Carolyn; Doel, Peter; Yao, Jun; Brooks, David; Thompson, Samantha; Willingale, Richard; Feldman, Charlotte; Button, Tim; Zhang, Dou; James, Ady

    2007-12-01

    The Smart X-ray Optics project is a UK based consortium consisting of several institutions to investigate the application of active/adaptive optics upon both small and large scale grazing incidence x-ray optics. The work done at University College London (UCL) focuses on the application of piezoelectric materials to large scale optics in order to actively deform the mirror's surface. These optics are geared towards the next generation of x-ray telescopes and it is hoped that the project will be able to achieve a resolution greater than that currently available by Chandra (0.5"). One of the aims of the consortium is to produce a working prototype. The initial design is based on a thin nickel ellipsoid segment with an x-ray reflective coating, on the back of which will be bonded a series of piezoelectric actuators. Investigation into the specification of the design of an active x-ray optic prototype and suitable support test structure has been undertaken. The dimensions and constraints upon the prototype, and the manufacturing process to produce a nickel shell are discussed. Finite element analysis (FEA) of the physical characteristics of piezoelectric materials has shown the ability to deform the nickel surface to correct for errors of several microns. FEA has also been utilised in the specification of the prototype's support structure to ensure that gravitational sag upon the optic is kept to a minimum. Laboratory experiments have tested a series of materials, different actuators and bonding methods, which could then be applied to the prototype.

  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. 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.

  20. CHP REGIONAL APPLICATION CENTERS: ACTIVITIES AND SELECTED RESULTS

    SciTech Connect

    Schweitzer, Martin

    2010-08-01

    Between 2001 and 2005, the U.S. Department of Energy (DOE) created a set of eight Regional Application Centers (RACs) to facilitate the development and deployment of Combined Heat and Power (CHP) technologies. By utilizing the thermal energy that is normally wasted when electricity is produced at central generating stations, Combined Heat and Power installations can save substantial amounts of energy compared to more traditional technologies. In addition, the location of CHP facilities at or near the point of consumption greatly reduces or eliminates electric transmission and distribution losses. The regional nature of the RACs allows each one to design and provide services that are most relevant to the specific economic and market conditions in its particular geographic area. Between them, the eight RACs provide services to all 50 states and the District of Columbia. Through the end of the federal 2009 fiscal year (FY 2009), the primary focus of the RACs was on providing CHP-related information to targeted markets, encouraging the creation and adoption of public policies and incentives favorable to CHP, and providing CHP users and prospective users with technical assistance and support on specific projects. Beginning with the 2010 fiscal year, the focus of the regional centers broadened to include district energy and waste heat recovery and these entities became formally known as Clean Energy Application Centers, as required by the Energy Independence and Security Act (EISA) of 2007. In 2007, ORNL led a cooperative effort to establish metrics to quantify the RACs accomplishments. That effort began with the development of a detailed logic model describing RAC operations and outcomes, which provided a basis for identifying important activities and accomplishments to track. A data collection spreadsheet soliciting information on those activities for FY 2008 and all previous years of RAC operations was developed and sent to the RACs in the summer of 2008. This

  1. Benchmark Active Controls Technology (BACT) Wing CFD Results

    NASA Technical Reports Server (NTRS)

    Schuster, David M.; Bartels, Robert E.

    2000-01-01

    The Benchmark Active Controls Technology (BACT) wing test (see chapter 8E) provides data for the validation of aerodynamic, aeroelastic, and active aeroelastic control simulation codes. These data provide a rich database for development and validation of computational aeroelastic and aeroservoelastic methods. In this vein, high-level viscous CFD analyses of the BACT wing have been performed for a subset of the test conditions available in the dataset. The computations presented in this section investigate the aerodynamic characteristics of the rigid clean wing configuration as well as simulations of the wing with a static and oscillating aileron and spoiler deflection. Two computational aeroelasticity codes extensively used at NASA Langley Research Center are implemented in this simulation. They are the ENS3DAE and CFL3DAE computational aeroelasticity programs. Both of these methods solve the three-dimensional compressible Navier-Stokes equations for both rigid and flexible vehicles, but they use significantly different approaches to the solution 6f the aerodynamic equations of motion. Detailed descriptions of both methods are presented in the following section.

  2. 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.

  3. 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

  4. 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.

  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. PMID:23180596

  6. 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.

  7. Selective photoregulation of the activity of glycogen synthase and glycogen phosphorylase, two key enzymes in glycogen metabolism.

    PubMed

    Díaz-Lobo, Mireia; Garcia-Amorós, Jaume; Fita, Ignacio; Velasco, Dolores; Guinovart, Joan J; Ferrer, Joan C

    2015-07-14

    Glycogen is a polymer of α-1,4- and α-1,6-linked glucose units that provides a readily available source of energy in living organisms. Glycogen synthase (GS) and glycogen phosphorylase (GP) are the two enzymes that control, respectively, the synthesis and degradation of this polysaccharide and constitute adequate pharmacological targets to modulate cellular glycogen levels, by means of inhibition of their catalytic activity. Here we report on the synthesis and biological evaluation of a selective inhibitor that consists of an azobenzene moiety glycosidically linked to the anomeric carbon of a glucose molecule. In the ground state, the more stable (E)-isomer of the azobenzene glucoside had a slight inhibitory effect on rat muscle GP (RMGP, IC50 = 4.9 mM) and Escherichia coli GS (EcGS, IC50 = 1.6 mM). After irradiation and subsequent conversion to the (Z)-form, the inhibitory potency of the azobenzene glucoside did not significantly change for RMGP (IC50 = 2.4 mM), while its effect on EcGS increased 50-fold (IC50 = 32 μM). Sucrose synthase 4 from potatoes, a glycosyltransferase that does not operate on glycogen, was only slightly inhibited by the (E)-isomer (IC50 = 0.73 mM). These findings could be rationalized on the basis of kinetic and computer-aided docking analysis, which indicated that both isomers of the azobenzene glucoside mimic the EcGS acceptor substrate and exert their inhibitory effect by binding to the glycogen subsite in the active center of the enzyme. The ability to selectively photoregulate the catalytic activity of key enzymes of glycogen metabolism may represent a new approach for the treatment of glycogen metabolism disorders.

  8. European activities in exobiology in earth orbit: results and perspectives

    NASA Astrophysics Data System (ADS)

    Horneck, G.

    1999-01-01

    A large portion of European activities in Earth orbit have concentrated on studies of the responses of resistant microbes to the harsh environment of space with the aim of providing experimental evidence testing the hypothesis that interplanetary transfer of life is possible. Various types of microorganisms, such as bacterial or fungal spores, as well as viruses and biomolecules, such as DNA, amino acids and liposomes, have been exposed to selected and combined space conditions outside the Earth's magnetic field (Apollo 16) or in low Earth orbit (Spacelab 1, Spacelab D2, ERA on EURECA, LDEF, BIOPAN on FOTON). Space parameters, such as high vacuum, intense solar ultraviolet radiation, different components of the cosmic radiation field and temperature extremes affected the genetic stability of the organisms in space, leading to increased mutation rates, DNA damage and inactivation. Extraterrestrial solar UV radiation was the most lethal factor. If shielded against the influx of solar UV, spores of Bacillus subtilis survived for more than 5 years in space. Future research will be directed towards long-term studies of microbes in artificial meteorites, as well as of microbial communities from special ecological niches, such as endolithic and endoevaporitic ecosystems. For these studies, the European Space Agency will provide the facility EXPOSE to be accommodated on the External Platform of the International Space Station during the Early Utilization Phase.

  9. 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

  10. 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.

  11. United States radiological health activities: inspection results of mammography facilities

    PubMed Central

    Spelic, DC; Kaczmarek, RV; Hilohi, M; Belella, S

    2007-01-01

    Purpose: The Mammography Quality Standards Act (MQSA) was enacted in 1992 to set national standards for high-quality mammography, including standards for mammographic X-ray equipment, patient dose, clinical image quality, and related technical parameters. The MQSA also requires minimum qualifications for radiologic technologists, interpreting physicians and medical physicists, mandates acceptable practices for quality-control, quality-assurance, and requires processes to audit medical outcomes. This paper presents the findings of MQSA inspections of facilities, which characterize significant factors affecting mammography quality in the United States. Materials and Methods: Trained inspectors collected data regarding X-ray technical factors, made exposure measurements for the determination of mean glandular dose (MGD), evaluated image quality, and inspected the quality of the film-processing environment. The average annual facility and total U.S. screening exam workloads were computed using workload data reported by facilities. Results: Mammography facilities have made technical improvements as evidenced by a narrower distribution of doses, higher phantom-film background optical densities associated with higher phantom image-quality scores, and better film processing. It is estimated that approximately 36 million screening mammography exams were conducted in 2006, a rate that is almost triple the exam volume estimated for 1997. Digital mammography (DM) is now in use at approximately 14% (1,191 of 8,834) of MQSA-certified mammography facilities. The results indicate that DM can offer lower dose to the patient while providing comparable or better image quality. PMID:21614276

  12. 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.

  13. 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.

  14. 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

  15. Results of mobile gamma scanning activities in St. Louis, Missouri

    SciTech Connect

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

    1991-06-01

    From 1942 through approximately 1966, the Mallinckrodt Chemical Works operated four plants in St. Louis, Missouri, for the Manhattan Engineer District and the Atomic Energy Commission. A variety of production processes using uranium- and radium-bearing ore materials were performed at the plants. It is the policy of the 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 Mallinckrodt properties have been previously investigated to determine the extent of on-site radiological contamination. At the request of DOE, Oak Ridge National Laboratory (ORNL) conducted a survey in May 1990, of public roadways and suspected haul routes between the Mallinckrodt plant and storage sites in St. Louis to ensure that no residual radioactive materials were conveyed off-site. A mobile gamma scanning van with an on-board computer system was used to identify possible anomalies. Suspect areas are those displaying measurements deviating from gamma exposure rates identified as typical for radiologically unenhanced areas in the vicinity of the areas of interest. The instrumentation highlighted three anomaly locations each of which measured less than 1m{sup 2} in size. None of the slightly elevated radiation levels originated from material associated with former AEC-related processing operations in the area. The anomalies resulted from elevated concentrations of radionuclides present in phosphate fertilizers, increased thorium in road-base gravel, and emanations from the radioactive storage site near the Latty Avenue airport. 9 refs., 3 figs.

  16. 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.

  17. 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

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

    PubMed

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

    2015-07-06

    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.

  19. Identification of a key catalytic intermediate demonstrates that nitrogenase is activated by the reversible exchange of N₂ for H₂.

    PubMed

    Lukoyanov, Dmitriy; Yang, Zhi-Yong; Khadka, Nimesh; Dean, Dennis R; Seefeldt, Lance C; Hoffman, Brian M

    2015-03-18

    Freeze-quenching nitrogenase during turnover with N2 traps an S = ½ intermediate that was shown by ENDOR and EPR spectroscopy to contain N2 or a reduction product bound to the active-site molybdenum-iron cofactor (FeMo-co). To identify this intermediate (termed here EG), we turned to a quench-cryoannealing relaxation protocol. The trapped state is allowed to relax to the resting E0 state in frozen medium at a temperature below the melting temperature; relaxation is monitored by periodically cooling the sample to cryogenic temperature for EPR analysis. During -50 °C cryoannealing of EG prepared under turnover conditions in which the concentrations of N2 and H2 ([H2], [N2]) are systematically and independently varied, the rate of decay of EG is accelerated by increasing [H2] and slowed by increasing [N2] in the frozen reaction mixture; correspondingly, the accumulation of EG is greater with low [H2] and/or high [N2]. The influence of these diatomics identifies EG as the key catalytic intermediate formed by reductive elimination of H2 with concomitant N2 binding, a state in which FeMo-co binds the components of diazene (an N-N moiety, perhaps N2 and two [e(-)/H(+)] or diazene itself). This identification combines with an earlier study to demonstrate that nitrogenase is activated for N2 binding and reduction through the thermodynamically and kinetically reversible reductive-elimination/oxidative-addition exchange of N2 and H2, with an implied limiting stoichiometry of eight electrons/protons for the reduction of N2 to two NH3. PMID:25741750

  20. Differential and Active Charging Results from the ATS Spacecraft.

    NASA Astrophysics Data System (ADS)

    Olsen, Richard Christopher

    1980-12-01

    This study of spacecraft charging concentrates on the differential charging and artificial particle emission experiments on ATS-5 and ATS-6. It was found that differential charging of spacecraft surfaces generated large electrostatic barriers to spacecraft generated electrons, from photoemission, secondary emission, and thermal emitters. The electrostatic barrier is a potential minimum outside the charged spacecraft which causes low energy electrons to be trapped near the spacecraft. The large dish antenna on ATS-6 was identified as the source of the electrostatic barrier around the Environmental Measurements Experiment package. Daylight charging on ATS-6 was shown to have behavior suggesting the dominance of differential charging on the absolute potential of the mainframe. Electron emission experiments on ATS-5 in eclipse charging environments showed that the electron emitter could partially or totally discharge the satellite, but the mainframe recharged negatively in a few 10's of seconds. The equilibrium emitter current was found to be .3 microamps, substantially below the milliamp capability of the emitter. The limiting of the current and the time dependence seen in the ATS-5 potential during these operations were explained as the result of differential charging of the insulating surfaces on the spacecraft, and the creation of an electrostatic barrier by the differential potential. This barrier limited the artificially generated electron current to the point that the net flux to the spacecraft was again negative. Both the daylight charging events of ATS-6 and the eclipse electron emission experiments of ATS-5 were further analyzed with a simple time dependent model which showed that the barrier height quickly reached an equilibrium value which limited but did not completely stop electron emission. Average and differential potentials developed in time subject to the constraint that the barrier height remain constant. Ion engine operations and plasma emission

  1. 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.

  2. 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…

  3. 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

  4. Absence of effects of dietary wheat bran on the activities of some key enzymes of carbohydrate and lipid metabolism in mouse liver and adipose tissue.

    PubMed

    Stanley, J C; Lambadarios, J A; Newsholme, E A

    1986-03-01

    1. The effects of a 100 g/kg dietary substitution of wheat bran on the body-weight gain, food consumption and faecal dry weight of mice given a high-sucrose diet and on the activities of some key enzymes of carbohydrate and lipid metabolism in liver and adipose tissue were studied. 2. Wheat bran had no effect on body-weight gain, food consumption or faecal dry weight. 3. Wheat bran had no effect on the activities of hepatic glucose-6-phosphate dehydrogenase (EC 1.1.1.49), 6-phosphogluconate dehydrogenase (EC 1.1.1.44), malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+) (EC 1.1.1.40), ATP-citrate (pro-3S)-lyase (EC 4.1.3.8), pyruvate kinase (EC 2.7.1.40) and fructose-1,6-bisphosphatase (EC 3.1.3.11). The activity of hepatic 6-phosphofructokinase (EC 2.7.1.11) increased but only when expressed on a body-weight basis. 4. Wheat bran had no effect on the activities of adipose tissue glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase, malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+), ATP-citrate (pro-3S)-lyase, hexokinase (EC 2.7.1.1), 6-phosphofructokinase and pyruvate kinase. 5. These results suggest that unlike guar gum and bagasse, wheat bran does not change the flux through some pathways of lipogenesis in liver and adipose tissue when mice are given high-sucrose diets.

  5. Unscheduled Akt-Triggered Activation of Cyclin-Dependent Kinase 2 as a Key Effector Mechanism of Apoptin's Anticancer Toxicity▿

    PubMed Central

    Maddika, Subbareddy; Panigrahi, Soumya; Wiechec, Emilia; Wesselborg, Sebastian; Fischer, Ute; Schulze-Osthoff, Klaus; Los, Marek

    2009-01-01

    Apoptin, a protein from the chicken anemia virus, has attracted attention because it specifically kills tumor cells while leaving normal cells unharmed. The reason for this tumor selectivity is unclear and depends on subcellular localization, as apoptin resides in the cytoplasm of normal cells but in the nuclei of transformed cells. It was shown that nuclear localization and tumor-specific killing crucially require apoptin's phosphorylation by an as yet unknown kinase. Here we elucidate the pathway of apoptin-induced apoptosis and show that it essentially depends on abnormal phosphatidylinositol 3-kinase (PI3-kinase)/Akt activation, resulting in the activation of the cyclin-dependent kinase CDK2. Inhibitors as well as dominant-negative mutants of PI3-kinase and Akt not only inhibited CDK2 activation but also protected cells from apoptin-induced cell death. Akt activated CDK2 by direct phosphorylation as well as by the phosphorylation-induced degradation of the inhibitor p27Kip1. Importantly, we also identified CDK2 as the principal kinase that phosphorylates apoptin and is crucially required for apoptin-induced cell death. Immortalized CDK2-deficient fibroblasts and CDK2 knockdown cells were markedly protected against apoptin. Thus, our results not only decipher the pathway of apoptin-induced cell death but also provide mechanistic insights for the selective killing of tumor cells. PMID:19103742

  6. Site-directed mutagenesis of the glycine-rich loop of death associated protein kinase (DAPK) identifies it as a key structure for catalytic activity.

    PubMed

    McNamara, Laurie K; Brunzelle, Joseph S; Schavocky, James P; Watterson, D Martin; Grum-Tokars, Valerie

    2011-05-01

    Death associated protein kinase (DAPK) is a calmodulin (CaM)-regulated protein kinase that is a therapeutic target for central nervous system (CNS) disorders. We report here the results of studies that test the hypothesis of McNamara et al. (2009) that conformational selection in DAPK's glycine-rich region is key for catalytic activity. The hypothesis was tested by site-directed mutagenesis of glutamine-23 (Q23) in the middle of this loop. The glycine-rich loop exhibits localized differences in structure among DAPK conformations that correlate with different stages of the catalytic cycle. Changing the Q23 to a Valine (V23), found at the corresponding position in another CaM regulated protein kinase, results in a reduced catalytic efficiency. High resolution X-ray crystal structures of various conformations of the Q23V mutant DAPK and their superimposition with the corresponding conformations from wild type catalytic domain reveal localized changes in the glycine-rich region. The effect of the mutation on DAPK catalytic activity and the finding of only localized changes in the DAPK structure provide experimental evidence implicating conformational selection in this domain with activity. This article is part of a Special Issue entitled: 11th European Symposium on Calcium.

  7. Copper(II) Ions Increase Plasminogen Activator Inhibitor Type 1 Dynamics in Key Structural Regions That Govern Stability.

    PubMed

    Bucci, Joel C; Trelle, Morten Beck; McClintock, Carlee S; Qureshi, Tihami; Jørgensen, Thomas J D; Peterson, Cynthia B

    2016-08-01

    Plasminogen activator inhibitor type 1 (PAI-1) regulates the fibrinolysis pathway by inhibiting the protease activity of plasminogen activators. PAI-1 works in concert with vitronectin (VN), an extracellular protein that aids in localization of active PAI-1 to tissues. The Peterson laboratory demonstrated that Cu(II) and other transition metals modulate the stability of PAI-1, exhibiting effects that are dependent on the presence or absence of the somatomedin B (SMB) domain of VN. The study presented here dissects the changes in molecular dynamics underlying the destabilizing effects of Cu(II) on PAI-1. We utilize backbone amide hydrogen/deuterium exchange monitored by mass spectrometry to assess PAI-1 dynamics in the presence and absence of Cu(II) ions with and without the SMB domain of VN. We show that Cu(II) produces an increase in dynamics in regions important for the function and overall stability of PAI-1, while the SMB domain elicits virtually the opposite effect. A mutant form of PAI-1 lacking two N-terminal histidine residues at positions 2 and 3 exhibits similar increases in dynamics upon Cu(II) binding compared to that of active wild-type PAI-1, indicating that the observed structural effects are not a result of coordination of Cu(II) to these histidine residues. Finally, addition of Cu(II) results in an acceleration of the local unfolding kinetics of PAI-1 presumed to be on pathway to the latency conversion. The effect of ligands on the dynamics of PAI-1 adds another intriguing dimension to the mechanisms for regulation of PAI-1 stability and function. PMID:27416303

  8. Copper(II) Ions Increase Plasminogen Activator Inhibitor Type 1 Dynamics in Key Structural Regions That Govern Stability.

    PubMed

    Bucci, Joel C; Trelle, Morten Beck; McClintock, Carlee S; Qureshi, Tihami; Jørgensen, Thomas J D; Peterson, Cynthia B

    2016-08-01

    Plasminogen activator inhibitor type 1 (PAI-1) regulates the fibrinolysis pathway by inhibiting the protease activity of plasminogen activators. PAI-1 works in concert with vitronectin (VN), an extracellular protein that aids in localization of active PAI-1 to tissues. The Peterson laboratory demonstrated that Cu(II) and other transition metals modulate the stability of PAI-1, exhibiting effects that are dependent on the presence or absence of the somatomedin B (SMB) domain of VN. The study presented here dissects the changes in molecular dynamics underlying the destabilizing effects of Cu(II) on PAI-1. We utilize backbone amide hydrogen/deuterium exchange monitored by mass spectrometry to assess PAI-1 dynamics in the presence and absence of Cu(II) ions with and without the SMB domain of VN. We show that Cu(II) produces an increase in dynamics in regions important for the function and overall stability of PAI-1, while the SMB domain elicits virtually the opposite effect. A mutant form of PAI-1 lacking two N-terminal histidine residues at positions 2 and 3 exhibits similar increases in dynamics upon Cu(II) binding compared to that of active wild-type PAI-1, indicating that the observed structural effects are not a result of coordination of Cu(II) to these histidine residues. Finally, addition of Cu(II) results in an acceleration of the local unfolding kinetics of PAI-1 presumed to be on pathway to the latency conversion. The effect of ligands on the dynamics of PAI-1 adds another intriguing dimension to the mechanisms for regulation of PAI-1 stability and function.

  9. 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

  10. 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

  11. 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)

  12. Key changes in wine aroma active compounds during bottle storage of Spanish red wines under different oxygen levels.

    PubMed

    Ferreira, Vicente; Bueno, Mónica; Franco-Luesma, Ernesto; Culleré, Laura; Fernández-Zurbano, Purificación

    2014-10-15

    Samples from 16 Spanish red wines have been stored for 6 months at 25 °C under different levels of oxygen (0-56 mg/L). Amino acids, metals, and phenolic compounds were analyzed and related to the production or depletion of key oxidation- and reduction-related aroma compounds. Oxidation brings about sensory-relevant increases in Strecker aldehydes, 1-octen-3-one, and vanillin. Formation of Strecker aldehydes correlates to the wine content on the corresponding amino acid precursor, Zn, and caffeic acid ethyl ester and negatively to some flavonols and anthocyanin derivatives. Formation of most carbonyls correlates to wine-combined SO2, suggesting that part of the increments are the result of the release of aldehydes forming bisulfite combinations once SO2 is oxidized. Methanethiol (MeSH) and dimethylsulfide (DMS), but not H2S levels, increase during storage. MeSH increments correlate to methionine levels and proanthocyanidins and negatively to resveratrol and aluminum. H2S, MeSH, and DMS levels all decreased with oxidation, and for the latter two, there are important effects of Mn and pH, respectively.

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

    PubMed

    Čipčić Paljetak, Hana; 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

    2016-09-01

    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.

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

    PubMed

    Čipčić Paljetak, Hana; 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

    2016-09-01

    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. Local Inflammation, Dissemination and Coalescence of Lesions Are Key for the Progression toward Active Tuberculosis: The Bubble Model

    PubMed Central

    Prats, Clara; Vilaplana, Cristina; Valls, Joaquim; Marzo, Elena; Cardona, Pere-Joan; López, Daniel

    2016-01-01

    The evolution of a tuberculosis (TB) infection toward active disease is driven by a combination of factors mostly related to the host response. The equilibrium between control of the bacillary load and the pathology generated is crucial as regards preventing the growth and proliferation of TB lesions. In addition, some experimental evidence suggests an important role of both local endogenous reinfection and the coalescence of neighboring lesions. Herein we propose a mathematical model that captures the essence of these factors by defining three hypotheses: (i) lesions grow logistically due to the inflammatory reaction; (ii) new lesions can appear as a result of extracellular bacilli or infected macrophages that escape from older lesions; and (iii) lesions can merge when they are close enough. This model was implemented in Matlab to simulate the dynamics of several lesions in a 3D space. It was also fitted to available microscopy data from infected C3HeB/FeJ mice, an animal model of active TB that reacts against Mycobacterium tuberculosis with an exaggerated inflammatory response. The results of the simulations show the dynamics observed experimentally, namely an initial increase in the number of lesions followed by fluctuations, and an exponential increase in the mean area of the lesions. In addition, further analysis of experimental and simulation results show a strong coincidence of the area distributions of lesions at day 21, thereby highlighting the consistency of the model. Three simulation series removing each one of the hypothesis corroborate their essential role in the dynamics observed. These results demonstrate that three local factors, namely an exaggerated inflammatory response, an endogenous reinfection, and a coalescence of lesions, are needed in order to progress toward active TB. The failure of one of these factors stops induction of the disease. This mathematical model may be used as a basis for developing strategies to stop the progression of

  16. The effect of dietary bagasse on the activities of some key enzymes of carbohydrate and lipid metabolism in mouse liver.

    PubMed

    Stanley, J C; Newsholme, E A

    1985-09-01

    The effects of a 100 g/kg diet substitution of bagasse on the body-weight gain, food consumption and faecal dry weight of mice given a high-sucrose diet and on the activities of hepatic glucose-6-phosphate dehydrogenase (EC I.I.I.49), 6-phosphogluconate dehydrogenase (EC I.I.I.44), malate dehydrogenase (oxaloacetate-decarboxylating) (NADP+) (EC I.I.I.40), ATP-citrate (pro-3S) lyase (EC 4.I.3.8), 6-phosphofructokinase EC 2.7.I.II), pyruvate kinase (EC 2.7.I.40) and fructose-1,6-bisphosphatase (EC 3.I.3.II) were studied. Bagasse had no effect on body-weight gain, food consumption or faecal dry weight. Bagasse decreased the activities of glucose-6-phosphate dehydrogenase, 6-phosphogluconate dehydrogenase and phosphofructokinase expressed on a wet weight basis and on a protein basis. Bagasse decreased the activities of glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase expressed on a body-weight basis. These results suggest that bagasse decreases the flux through some pathways of hepatic lipogenesis when mice are given high-sucrose diets.

  17. Dentin Sialophosphoprotein (DSPP) Gene-Silencing Inhibits Key Tumorigenic Activities in Human Oral Cancer Cell Line, OSC2

    PubMed Central

    Joshi, Rajeshree; Tawfik, Amany; Edeh, Nneka; McCloud, Veronica; Looney, Stephen; Lewis, Jill; Hsu, Stephen; Ogbureke, Kalu U. E.

    2010-01-01

    Background We determined recently that dentin sialophosphoprotein (DSPP), a member of the SIBLING (Small integrin-binding ligand N-linked glycoproteins) family of phosphoglycoproteins, is highly upregulated in human oral squamous cell carcinomas (OSCCs) where upregulation is associated with tumor aggressiveness. To investigate the effects of DSPP-silencing on the tumorigenic profiles of the oral cancer cell line, OSC2, short-hairpin RNA (shRNA) interference was employed to silence DSPP in OSC2 cells. Methodology/Principal Findings Multiple regions of DSPP transcript were targeted for shRNA interference using hDSP-shRNA lentiviral particles designed to silence DSPP gene expression. Control shRNA plasmid encoding a scrambled sequence incapable of degrading any known cellular mRNA was used for negative control. Following puromycin selection of stable lines of DSSP-silenced OSC2 cells, phenotypic hallmarks of oral carcinogenesis were assayed by western blot and RT-PCR analyses, MTT (cell-viability), colony-formation, modified Boyden-Chamber (migration and invasion), and flow cytometry (cell-cycle and apoptosis) analyses. DSPP-silenced OSC2 cells showed altered cell morphology, reduced viability, decreased colony-formation ability, decreased migration and invasion, G0/G1 cell-cycle arrest, and increased tumor cell sensitivity to cisplatin-induced apoptosis. Furthermore, MMP-2, MMP-3, MMP-9, VEGF, Ki-67, p53, and EGFR were down-regulated. There was a direct correlation between the degree of DSPP-silencing and MMP suppression, as indicated by least squares regression: MMP-2 {(y = 0.850x, p<0.001) (y = 1.156x, p<0.001)}, MMP-3 {(y = 0.994x, p<0.001) (y = 1.324x, p = 0.004)}, and MMP-9 {(y = 1.248x, p = 0.005, y = 0.809, p = 0.013)}. Conclusions/Significance DSPP-silencing in OSC2 cell decreased salient hallmarks of oral tumorigenesis and provides the first functional evidence of a potential key role for DSPP in oral cancer biology. The

  18. 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'.

  19. 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 Central

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

    2014-01-01

    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. PMID:24675475

  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

    2014-07-01

    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. The NASA Soil Moisture Active Passive (SMAP) Mission Status and Early Results

    NASA Astrophysics Data System (ADS)

    Entekhabi, D.; Yueh, S. H.; O'Neill, P. E.; Entin, J. K.; Njoku, E. G.; Kellogg, K.

    2015-12-01

    NASA's Soil Moisture Active Passive (SMAP) mission was launched on January 31, 2015. SMAP provides high-resolution, frequent revisit global mapping of soil moisture and freeze/thaw state based on coincident L-band radiometer and L-band radar measurements. The primary science goal of SMAP is to provide new perspectives on how the three fundamental cycles of the Earth system, the water, energy and carbon cycles, are linked together over land. Soil moisture is the key variable that links the three cycles and makes their co-variations synchronous in time. Soil moisture products with varying resolution and coverage are produced from the radiometer alone, radar alone, radiometer-radar combination and data assimilation. In this session the status of the SMAP observatory and early results based on the science data products will be included. The science data acquisition began in May 2015 following several weeks of observatory and instrument commissioning. An intense calibration and validation period followed. Preliminary science products on instrument measurements, soil moisture, landscape frozen or thawed status, and net ecosystem exchange are available at publicly-accessible data archives. The presentation will include early and summary results on the validation of these products. The instrument measurements can also be used to map sea-ice coverage, ocean surface winds and sea surface salinity. Examples of these global retrievals are also presented.

  2. Activation of RARα induces autophagy in SKBR3 breast cancer cells and depletion of key autophagy genes enhances ATRA toxicity

    PubMed Central

    Brigger, D; Schläfli, A M; Garattini, E; Tschan, M P

    2015-01-01

    All-trans retinoic acid (ATRA), a pan-retinoic acid receptor (RAR) agonist, is, along with other retinoids, a promising therapeutic agent for the treatment of a variety of solid tumors. On the one hand, preclinical studies have shown promising anticancer effects of ATRA in breast cancer; on the other hand, resistances occurred. Autophagy is a cellular recycling process that allows the degradation of bulk cellular contents. Tumor cells may take advantage of autophagy to cope with stress caused by anticancer drugs. We therefore wondered if autophagy is activated by ATRA in mammary tumor cells and if modulation of autophagy might be a potential novel treatment strategy. Indeed, ATRA induces autophagic flux in ATRA-sensitive but not in ATRA-resistant human breast cancer cells. Moreover, using different RAR agonists as well as RARα-knockdown breast cancer cells, we demonstrate that autophagy is dependent on RARα activation. Interestingly, inhibition of autophagy in breast cancer cells by either genetic or pharmacological approaches resulted in significantly increased apoptosis under ATRA treatment and attenuated epithelial differentiation. In summary, our findings demonstrate that ATRA-induced autophagy is mediated by RARα in breast cancer cells. Furthermore, inhibition of autophagy results in enhanced apoptosis. This points to a potential novel treatment strategy for a selected group of breast cancer patients where ATRA and autophagy inhibitors are applied simultaneously. PMID:26313912

  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. Modeling present hydrological conditions as a key to predict the future - results from a case study of a periglacial catchment in Greenland

    NASA Astrophysics Data System (ADS)

    Johansson, E.; Lindborg, T.; Berglund, S.

    2015-12-01

    The routing of water through periglacial landscapes is closely connected to the presence of permafrost, and freezing and thawing processes. To predict responses in the landscape to climate driven changes, we need to better understand the present day hydrology. The present hydrological processes, and the uncertainties in the data used to describe them, must be investigated and understood before we can develop models describing possible future conditions. In this work we have studied the hydrology of a catchment in the Kangerlussuaq region, Greenland. Johansson et al. (2015) presented a hydrological model of the catchment based on a new hydrological and meteorological data set from the catchment area. The present water balance was quantified, and the spatial and seasonal dynamics of the main hydrological fluxes were presented. It was shown that the model was able to reproduce the measured lake level dynamics and the measured components of the water balance. Based on this work we have used the numerical model to investigate the sensitivity in hydrological responses to different meteorological, geological and geometrical model input data. The aim with this study is to investigate the importance of the use of local data, but also to highlight the importance of present day site understanding when developing and applying the model for predicting responses to a changing climate. The results show that the site specific model is highly sensitive to the meteorological input data. Driving the model with precipitation data from a meteorological station only 30 km away from the catchment instead of local data from the studied catchment, or using local precipitation data not corrected for wind and adhesion losses, resulted in large discrepancies between measured and calculated lake levels. The modelled intra-annual dynamics of the active layer groundwater was shown to be sensitive both to the applied soil temperatures but also to the active layer depth and sediment stratigraphy.

  5. 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.

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

    NASA Astrophysics Data System (ADS)

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

    2015-10-01

    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.

  7. 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

  8. Putting Flow Theory into Educational Practice: The Key School's Flow Activities Room. Report to the Benton Center for Curriculum and Instruction, University of Chicago.

    ERIC Educational Resources Information Center

    Whalen, Samuel P.; Csikszentmihalyi, Mihaly

    The Key School in Indianapolis, an experimental elementary school, was founded by eight experienced teachers who believed that schools can be enjoyable as well as rigorous. This report focuses on one feature of the school, the Flow Activities Room (FAR). The development of the FAR was based on the school's commitment to the theories of multiple…

  9. Inhibitory activity on type 2 diabetes and hypertension key-enzymes, and antioxidant capacity of Veronica persica phenolic-rich extracts.

    PubMed

    Sharifi-Rad, M; Tayeboon, G S; Sharifi-Rad, J; Iriti, M; Varoni, E M; Razazi, S

    2016-05-30

    Veronica genus (Plantaginaceae) is broadly distributed in different habitats. In this study, the inhibitory activity of free soluble and conjugated phenolic extracts of Veronica persica on key enzymes associated to type 2 diabetes (α-glucosidase and α-amylase) and hypertension (angiotensin I converting enzyme, ACE) was assessed, as well as their antioxidant power. Our results showed that both the extracts inhibited α-amylase, α-glucosidase and ACE in a dose-dependent manner. In particular, free phenolic extract significantly (P<0.05) inhibited α-glucosidase (IC50 532.97 µg/mL), whereas conjugated phenolic extract significantly (P<0.05) inhibited α-amylase (IC50 489.73 µg/mL) and ACE (290.06 µg/mL). The enzyme inhibitory activities of the extracts were not associated with their phenolic content. Anyway, the inhibition of α-amylase, α-glucosidase and ACE, along with the antioxidant capacity of the phenolic-rich extracts, could represent a putative mechanism through which V. persica exerts its antidiabetes and antihypertension effects.

  10. 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

  11. Diversity and relationships in key traits for functional and apparent quality in a collection of eggplant: fruit phenolics content, antioxidant activity, polyphenol oxidase activity, and browning.

    PubMed

    Plazas, Mariola; López-Gresa, María P; Vilanova, Santiago; Torres, Cristina; Hurtado, Maria; Gramazio, Pietro; Andújar, Isabel; Herráiz, Francisco J; Bellés, José M; Prohens, Jaime

    2013-09-18

    Eggplant (Solanum melongena) varieties with increased levels of phenolics in the fruit present enhanced functional quality, but may display greater fruit flesh browning. We evaluated 18 eggplant accessions for fruit total phenolics content, chlorogenic acid content, DPPH scavenging activity, polyphenol oxidase (PPO) activity, liquid extract browning, and fruit flesh browning. For all the traits we found a high diversity, with differences among accessions of up to 3.36-fold for fruit flesh browning. Variation in total content in phenolics and in chlorogenic acid content accounted only for 18.9% and 6.0% in the variation in fruit flesh browning, and PPO activity was not significantly correlated with fruit flesh browning. Liquid extract browning was highly correlated with chlorogenic acid content (r = 0.852). Principal components analysis (PCA) identified four groups of accessions with different profiles for the traits studied. Results suggest that it is possible to develop new eggplant varieties with improved functional and apparent quality.

  12. Results and evaluation of key comparison CCM.P-K12.1 for very low helium flow rates (leak rates)

    NASA Astrophysics Data System (ADS)

    Šetina, Janez; Vičar, Martin; Pražák, Dominik

    2015-01-01

    The Czech Metrology Institute (CMI) took part and failed to prove equivalence in the Key Comparison CCM.P-K12 of helium leak artefacts (leak rates) into vacuum. After identifying and eliminating the cause of the failure, the Institute of Metals and Technology (IMT) of Slovenia, a successful participant in CCM.P-K12, volunteered to serve as pilot and link in a following bilateral comparison of IMT and CMI that obtained designation CCM.P-K12.1 in June 2012. It was decided to perform the comparison with a glass permeation helium leak artefact at nominally 3.10-11 mol/s (7.4.10-7 mbar.L.s-1) at 23 °C. Both the laboratory standards took part in CCM.P-K12 and were considered as primary. The comparison measurements were performed in October 2012. CMI proved equivalence both with IMT and with the reference value of the key comparison CCM.P-K12. 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 CCM, according to the provisions of the CIPM Mutual Recognition Arrangement (CIPM MRA).

  13. Key role of salsolinol in ethanol actions on dopamine neuronal activity of the posterior ventral tegmental area.

    PubMed

    Melis, Miriam; Carboni, Ezio; Caboni, Pierluigi; Acquas, Elio

    2015-01-01

    Ethanol excites dopamine (DA) neurons in the posterior ventral tegmental area (pVTA). This effect is responsible for ethanol's motivational properties and may contribute to alcoholism. Evidence indicates that catalase-mediated conversion of ethanol into acetaldehyde in pVTA plays a critical role in this effect. Acetaldehyde, in the presence of DA, condensates with it to generate salsolinol. Salsolinol, when administered in pVTA, excites pVTA DA cells, elicits DA transmission in nucleus accumbens and sustains its self-administration in pVTA. Here we show, by using ex vivo electrophysiology, that ethanol and acetaldehyde, but not salsolinol, failed to stimulate pVTA DA cell activity in mice administered α-methyl-p-tyrosine, a DA biosynthesis inhibitor that reduces somatodendritic DA release. This effect was specific for ethanol and acetaldehyde since morphine, similarly to salsolinol, was able to excite pVTA DA cells in α-methyl-p-tyrosine-treated mice. However, when DA was bath applied in slices from α-methyl-p-tyrosine-treated mice, ethanol-induced excitation of pVTA DA neurons was restored. This effect requires ethanol oxidation into acetaldehyde given that, when H2 O2 -catalase system was impaired by either 3-amino-1,2,4-triazole or in vivo administration of α-lipoic acid, ethanol did not enhance DA cell activity. Finally, high performance liquid chromatography-tandem mass spectrometry analysis of bath medium detected salsolinol only after co-application of ethanol and DA in α-methyl-p-tyrosine-treated mice. These results demonstrate the relationship between ethanol and salsolinol effects on pVTA DA neurons, help to untangle the mechanism(s) of action of ethanol in this area and contribute to an exciting research avenue prosperous of theoretical and practical consequences.

  14. Brachyury as a potential modulator of androgen receptor activity and a key player in therapy resistance in prostate cancer

    PubMed Central

    Pinto, Filipe; Pértega-Gomes, Nelma; Vizcaíno, José R.; Andrade, Raquel P.; Cárcano, Flavio M.; Reis, Rui Manuel

    2016-01-01

    Prostate cancer (PCa) is the most commonly diagnosed neoplasm and the second leading cause of cancer-related deaths in men. Acquisition of resistance to conventional therapy is a major problem for PCa patient management. Several mechanisms have been described to promote therapy resistance in PCa, such as androgen receptor (AR) activation, epithelial-to-mesenchymal transition (EMT), acquisition of stem cell properties and neuroendocrine transdifferentiation (NEtD). Recently, we identified Brachyury as a new biomarker of PCa aggressiveness and poor prognosis. In the present study we aimed to assess the role of Brachyury in PCa therapy resistance. We showed that Brachyury overexpression in prostate cancer cells lines increased resistance to docetaxel and cabazitaxel drugs, whereas Brachyury abrogation induced decrease in therapy resistance. Through ChiP-qPCR assays we further demonstrated that Brachyury is a direct regulator of AR expression as well as of the biomarker AMACR and the mesenchymal markers Snail and Fibronectin. Furthermore, in vitro Brachyury was also able to increase EMT and stem properties. By in silico analysis, clinically human Brachyury-positive PCa samples were associated with biomarkers of PCa aggressiveness and therapy resistance, including PTEN loss, and expression of NEtD markers, ERG and Bcl-2. Taken together, our results indicate that Brachyury contributes to tumor chemotherapy resistance, constituting an attractive target for advanced PCa patients. PMID:27049720

  15. The IGAC activity for the development of global emissions inventories: Description and initial results. Revision

    SciTech Connect

    Benkovitz, C.M.; Graedel, T.E.

    1992-02-01

    Modeling assessments of the atmospheric chemistry, air quality and climatic conditions of the past, present and future require as input inventories of emissions of the appropriate chemical species constructed on appropriate spatial and temporal scales. The task of the Global Emissions Inventories Activity (GEIA) of the International Global Atmospheric Chemistry Project (IGAC) is the production of global inventories suitable for a range of research applications. Current GEIA programs are generally based on addressing emissions by species; these include CO{sub 2}, NH{sub 3}/N{sub 2}O, SO{sub 2}/NO{sub x}, CFC, volatile organic compounds and radioisotopes. In addition a separate program to inventory emissions from biomass burning is also being structured, plus an additional program to address data management issues for all the developing inventories. Program priorities are based on current knowledge and tasks needed to produce the desired inventories. This paper will discuss the different types of global inventories to be developed by the GEIA programs, their key characteristics, and areas to be addressed in the compilation of such inventories. Results of the first GEIA task, a survey of existing inventories and auxiliary data, will be presented. The survey included status assessments for the available inventory information for nineteen different atmospheric species or groups of species on global and regional scales and over time. Of this entire body of information, the only inventory regarded as satisfactory was that for the global emissions of CFCs. An implication of the results of these assessments is that properly gridded emissions inventories are badly needed to support atmospheric modeling calculations on a variety of spatial and temporal scales. Initial studies in the development of global inventories of sulfur dioxide, currently the most advanced GEIA program, will be presented and discussed.

  16. The IGAC activity for the development of global emissions inventories: Description and initial results

    SciTech Connect

    Benkovitz, C.M. ); Graedel, T.E. )

    1992-02-01

    Modeling assessments of the atmospheric chemistry, air quality and climatic conditions of the past, present and future require as input inventories of emissions of the appropriate chemical species constructed on appropriate spatial and temporal scales. The task of the Global Emissions Inventories Activity (GEIA) of the International Global Atmospheric Chemistry Project (IGAC) is the production of global inventories suitable for a range of research applications. Current GEIA programs are generally based on addressing emissions by species; these include CO{sub 2}, NH{sub 3}/N{sub 2}O, SO{sub 2}/NO{sub x}, CFC, volatile organic compounds and radioisotopes. In addition a separate program to inventory emissions from biomass burning is also being structured, plus an additional program to address data management issues for all the developing inventories. Program priorities are based on current knowledge and tasks needed to produce the desired inventories. This paper will discuss the different types of global inventories to be developed by the GEIA programs, their key characteristics, and areas to be addressed in the compilation of such inventories. Results of the first GEIA task, a survey of existing inventories and auxiliary data, will be presented. The survey included status assessments for the available inventory information for nineteen different atmospheric species or groups of species on global and regional scales and over time. Of this entire body of information, the only inventory regarded as satisfactory was that for the global emissions of CFCs. An implication of the results of these assessments is that properly gridded emissions inventories are badly needed to support atmospheric modeling calculations on a variety of spatial and temporal scales. Initial studies in the development of global inventories of sulfur dioxide, currently the most advanced GEIA program, will be presented and discussed.

  17. 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.

  18. 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.

  19. 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).

  20. 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.

  1. AMP-activated protein kinase: a key regulator of energy balance with many roles in human disease.

    PubMed

    Grahame Hardie, D

    2014-12-01

    The AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that regulates cellular and whole-body energy balance. A recently reported crystal structure has illuminated the complex regulatory mechanisms by which AMP and ADP cause activation of AMPK, involving phosphorylation by the upstream kinase LKB1. Once activated by falling cellular energy status, AMPK activates catabolic pathways that generate ATP whilst inhibiting anabolic pathways and other cellular processes that consume ATP. A role of AMPK is implicated in many human diseases. Mutations in the γ2 subunit cause heart disease due to excessive glycogen storage in cardiac myocytes, leading to ventricular pre-excitation. AMPK-activating drugs reverse many of the metabolic defects associated with insulin resistance, and recent findings suggest that the insulin-sensitizing effects of the widely used antidiabetic drug metformin are mediated by AMPK. The upstream kinase LKB1 is a tumour suppressor, and AMPK may exert many of its antitumour effects. AMPK activation promotes the oxidative metabolism typical of quiescent cells, rather than the aerobic glycolysis observed in tumour cells and cells involved in inflammation, explaining in part why AMPK activators have both antitumour and anti-inflammatory effects. Salicylate (the major in vivo metabolite of aspirin) activates AMPK, and this could be responsible for at least some of the anticancer and anti-inflammatory effects of aspirin. In addition to metformin and salicylates, novel drugs that modulate AMPK are likely to enter clinical trials soon. Finally, AMPK may be involved in viral infection: downregulation of AMPK during hepatitis C virus infection appears to be essential for efficient viral replication. PMID:24824502

  2. Acetate Activation in Methanosaeta thermophila: Characterization of the Key Enzymes Pyrophosphatase and Acetyl-CoA Synthetase

    PubMed Central

    Berger, Stefanie; Welte, Cornelia; Deppenmeier, Uwe

    2012-01-01

    The thermophilic methanogen Methanosaeta thermophila uses acetate as sole substrate for methanogenesis. It was proposed that the acetate activation reaction that is needed to feed acetate into the methanogenic pathway requires the hydrolysis of two ATP, whereas the acetate activation reaction in Methanosarcina sp. is known to require only one ATP. As these organisms live at the thermodynamic limit that sustains life, the acetate activation reaction in Mt. thermophila seems too costly and was thus reevaluated. It was found that of the putative acetate activation enzymes one gene encoding an AMP-forming acetyl-CoA synthetase was highly expressed. The corresponding enzyme was purified and characterized in detail. It catalyzed the ATP-dependent formation of acetyl-CoA, AMP, and pyrophosphate (PPi) and was only moderately inhibited by PPi. The breakdown of PPi was performed by a soluble pyrophosphatase. This enzyme was also purified and characterized. The pyrophosphatase hydrolyzed the major part of PPi (KM = 0.27 ± 0.05 mM) that was produced in the acetate activation reaction. Activity was not inhibited by nucleotides or PPi. However, it cannot be excluded that other PPi-dependent enzymes take advantage of the remaining PPi and contribute to the energy balance of the cell. PMID:22927778

  3. Changes in the activities of key enzymes of glycolysis during the cell cycle in yeast: a rectification.

    PubMed

    de Koning, W; Groeneveld, K; Oehlen, L J; Berden, J A; van Dam, K

    1991-04-01

    Activities of glycolytic enzymes were determined in elutriation fractionated cultures of Saccharomyces cerevisiae grown on different carbon sources. Almost pure fractions of single cells at the G1 state of cell division were obtained for some of the growth conditions tested, whereas other stages were enriched in particular fractions. Specific activities of glucose-6-phosphate dehydrogenase and alcohol dehydrogenase were found to be constant during the cell cycle, as reported by van Doorn et al. (1988a), Journal of Bacteriology 170, 4808-4815, and (1988b), Journal of General Microbiology 134, 785-790. In contrast to the earlier reports, the activities of hexokinase, phosphofructokinase, pyruvate kinase and trehalase were also constant in different states of the cell cycle. For hexokinase and phosphofructokinase it was shown that the apparent specific activity in a cell-free extract strongly diminished when extracts contained less that 0.5-1 mg protein ml-1. In the experiments of van Doorn et al. (1988a) the protein content of the outer fractions was up to 20 times lower than that of the central fractions, suggesting an alternative explanation for the observed changes in enzyme activities during the cell cycle. Therefore, we want to rectify the observations presented by van Doorn et al. (1988a), and conclude that the activities of the glycolytic enzymes do not vary greatly during the cell cycle of S. cervisiae. PMID:1856683

  4. 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

  5. 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

  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

    2016-01-01

    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. Perinucleolar relocalization and nucleolin as crucial events in the transcriptional activation of key genes in mantle cell lymphoma.

    PubMed

    Allinne, Jeanne; Pichugin, Andrei; Iarovaia, Olga; Klibi, Manel; Barat, Ana; Zlotek-Zlotkiewicz, Ewa; Markozashvili, Diana; Petrova, Natalia; Camara-Clayette, Valérie; Ioudinkova, Elena; Wiels, Joëlle; Razin, Sergey V; Ribrag, Vincent; Lipinski, Marc; Vassetzky, Yegor S

    2014-03-27

    In mantle cell lymphoma (MCL), one allele of the cyclin D1 (Ccnd1) gene is translocated from its normal localization on chromosome 11 to chromosome 14. This is considered as the crucial event in the transformation process of a normal naive B-cell; however, the actual molecular mechanism leading to Ccnd1 activation remains to be deciphered. Using a combination of three-dimensional and immuno-fluorescence in situ hybridization experiments, the radial position of the 2 Ccnd1 alleles was investigated in MCL-derived cell lines and malignant cells from affected patients. The translocated Ccnd1 allele was observed significantly more distant from the nuclear membrane than its nontranslocated counterpart, with a very high proportion of IgH-Ccnd1 chromosomal segments localized next to a nucleolus. These perinucleolar areas were found to contain active RNA polymerase II (PolII) clusters. Nucleoli are rich in nucleolin, a potent transcription factor that we found to bind sites within the Ccnd1 gene specifically in MCL cells and to activate Ccnd1 transcription. We propose that the Ccnd1 transcriptional activation in MCL cells relates to the repositioning of the rearranged IgH-Ccnd1-carrying chromosomal segment in a nuclear territory with abundant nucleolin and active PolII molecules. Similar transforming events could occur in Burkitt and other B-cell lymphomas.

  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. PMID:26689172

  9. 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.

  10. 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…

  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 topics in…

  12. NADPH Oxidase Activity in Cerebral Arterioles Is a Key Mediator of Cerebral Small Vessel Disease-Implications for Prevention.

    PubMed

    McCarty, Mark F

    2015-01-01

    Cerebral small vessel disease (SVD), a common feature of brain aging, is characterized by lacunar infarcts, microbleeds, leukoaraiosis, and a leaky blood-brain barrier. Functionally, it is associated with cognitive decline, dementia, depression, gait abnormalities, and increased risk for stroke. Cerebral arterioles in this syndrome tend to hypertrophy and lose their capacity for adaptive vasodilation. Rodent studies strongly suggest that activation of Nox2-dependent NADPH oxidase activity is a crucial driver of these structural and functional derangements of cerebral arterioles, in part owing to impairment of endothelial nitric oxide synthase (eNOS) activity. This oxidative stress may also contribute to the breakdown of the blood-brain barrier seen in SVD. Hypertension, aging, metabolic syndrome, smoking, hyperglycemia, and elevated homocysteine may promote activation of NADPH oxidase in cerebral arterioles. Inhibition of NADPH oxidase with phycocyanobilin from spirulina, as well as high-dose statin therapy, may have potential for prevention and control of SVD, and high-potassium diets merit study in this regard. Measures which support effective eNOS activity in other ways-exercise training, supplemental citrulline, certain dietary flavonoids (as in cocoa and green tea), and capsaicin, may also improve the function of cerebral arterioles. Asian epidemiology suggests that increased protein intakes may decrease risk for SVD; conceivably, arginine and/or cysteine-which boosts tissue glutathione synthesis, and can be administered as N-acetylcysteine-mediate this benefit. Ameliorating the risk factors for SVD-including hypertension, metabolic syndrome, hyperglycemia, smoking, and elevated homocysteine-also may help to prevent and control this syndrome, although few clinical trials have addressed this issue to date. PMID:27417759

  13. NADPH Oxidase Activity in Cerebral Arterioles Is a Key Mediator of Cerebral Small Vessel Disease—Implications for Prevention

    PubMed Central

    McCarty, Mark F.

    2015-01-01

    Cerebral small vessel disease (SVD), a common feature of brain aging, is characterized by lacunar infarcts, microbleeds, leukoaraiosis, and a leaky blood-brain barrier. Functionally, it is associated with cognitive decline, dementia, depression, gait abnormalities, and increased risk for stroke. Cerebral arterioles in this syndrome tend to hypertrophy and lose their capacity for adaptive vasodilation. Rodent studies strongly suggest that activation of Nox2-dependent NADPH oxidase activity is a crucial driver of these structural and functional derangements of cerebral arterioles, in part owing to impairment of endothelial nitric oxide synthase (eNOS) activity. This oxidative stress may also contribute to the breakdown of the blood-brain barrier seen in SVD. Hypertension, aging, metabolic syndrome, smoking, hyperglycemia, and elevated homocysteine may promote activation of NADPH oxidase in cerebral arterioles. Inhibition of NADPH oxidase with phycocyanobilin from spirulina, as well as high-dose statin therapy, may have potential for prevention and control of SVD, and high-potassium diets merit study in this regard. Measures which support effective eNOS activity in other ways—exercise training, supplemental citrulline, certain dietary flavonoids (as in cocoa and green tea), and capsaicin, may also improve the function of cerebral arterioles. Asian epidemiology suggests that increased protein intakes may decrease risk for SVD; conceivably, arginine and/or cysteine—which boosts tissue glutathione synthesis, and can be administered as N-acetylcysteine—mediate this benefit. Ameliorating the risk factors for SVD—including hypertension, metabolic syndrome, hyperglycemia, smoking, and elevated homocysteine—also may help to prevent and control this syndrome, although few clinical trials have addressed this issue to date. PMID:27417759

  14. Electric utility/advocacy group interaction: A case history report on the key outcomes of DSM/IRP interactive efforts and related advocacy group activities

    SciTech Connect

    Schweitzer, M. ); English, M.; Schexnayder, S. . Energy, Environment and Resources Center); Altman, J.

    1995-01-01

    This article presents the findings derived from ten case studies of activities undertaken by energy efficiency advocacy groups (EEAGs) to influence the use of cost-effective Demand-Side Management (DSM) by electric utilities and to promote Integrated Resource Planning (IRP). Nine of these ten cases included some form of interactive effort involving utilities and, in almost all cases, other nonutility parties (NUPs) as well. All ten cases also included other EEAG activities. Key findings of the study include the following: interactive efforts had substantially greater effects on utility DSM usage and on relations among the involved parties than on regulatory policy; other EEAG activities had the great effect on regulatory policy and the least direct effect on utility DSM usage; and the discernible overall effects of interactive efforts were somewhat greater than those of the EEAGs' other activities, which often had less tangible and immediate effects.

  15. Communication is key: Reducing DEK1 activity reveals a link between cell-cell contacts and epidermal cell differentiation status.

    PubMed

    Galletti, Roberta; Ingram, Gwyneth C

    2015-01-01

    Plant epidermis development requires not only the initial acquisition of tissue identity, but also the ability to differentiate specific cell types over time and to maintain these differentiated states throughout the plant life. To set-up and maintain differentiation, plants activate specific transcriptional programs. Interfering with these programs can prevent differentiation and/or force differentiated cells to lose their identity and re-enter a proliferative state. We have recently shown that the Arabidopsis Defective Kernel 1 (DEK1) protein is required both for the differentiation of epidermal cells and for the maintenance of their fully differentiated state. Defects in DEK1 activity lead to a deregulation of the expression of epidermis-specific differentiation-promoting HD-ZIP IV transcription factors. Here we propose a working model in which DEK1, by maintaining cell-cell contacts, and thus communication between neighboring cells, influences HD-ZIP IV gene expression and epidermis differentiation. PMID:27064205

  16. 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

  17. Activity of key enzymes in microsomal and mitochondrial membranes depends on the redox reactions involving lipid radicals.

    PubMed

    Dmitriev, L F

    2001-07-01

    The work reviews membrane processes, such as monooxygenase reaction and oxidative phosphorylation with special reference to hydroxylation of a xenobiotic benzo(a)pyrene and the effects of the radical scavenger propyl gallate and radical generator Fe2+ ions on the reaction kinetics. A possibility is discussed that tocopherol provides for the activity of the lipid-radical cycles involving cytochrome b5. The lipid-radical cycles protect membrane lipids from oxidation and control the kinetics of membrane processes. The NADPH oxidation energy is transformed into the energy of lipid pulsations and this energy is used for activation of membrane enzymes. To account for the role of lipid pulsations in membrane processes, a new parameter is introduced - the internal temperature. It is supposed that there should be the equilibrium between the pro- and antioxidant factors in the membranes, and the presence of exogenous antioxidants (propyl gallate etc.) should be considered as a negative factor. PMID:11699868

  18. Towards predicting the lung fibrogenic activity of MWCNT: Key role of endocytosis, kinase receptors and ERK 1/2 signaling.

    PubMed

    Vietti, Giulia; Ibouraadaten, Saloua; Palmai-Pallag, Mihaly; Yakoub, Yousof; Piret, Jean-Pascal; Marbaix, Etienne; Lison, Dominique; van den Brule, Sybille

    2016-01-01

    Carbon nanotubes (CNT) have been reported to induce lung inflammation and fibrosis in rodents. We investigated the direct and indirect cellular mechanisms mediating the fibrogenic activity of multi-wall (MW) CNT on fibroblasts. We showed that MWCNT indirectly stimulate lung fibroblast (MLg) differentiation, via epithelial cells and macrophages, whereas no direct effect of MWCNT on fibroblast differentiation or collagen production was detected. MWCNT directly stimulated the proliferation of fibroblasts primed with low concentrations of growth factors, such as PDGF, TGF-β or EGF. MWCNT prolonged ERK 1/2 phosphorylation induced by low concentrations of PDGF or TGF-β in fibroblasts. This phenomenon and the proliferative activity of MWCNT on fibroblasts was abrogated by the inhibitors of ERK 1/2, PDGF-, TGF-β- and EGF-receptors. This activity was also reduced by amiloride, an endocytosis inhibitor. Finally, the lung fibrotic response to several MWCNT samples (different in length and diameter) correlated with their in vitro capacity to stimulate the proliferation of fibroblasts and to prolong ERK 1/2 signaling in these cells. Our findings point to a crosstalk between MWCNT, kinase receptors, ERK 1/2 signaling and endocytosis which stimulates the proliferation of fibroblasts. The mechanisms of action identified in this study contribute to predict the fibrogenic potential of MWCNT.

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

    PubMed

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

    2014-09-01

    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. PMID:25195876

  20. Oocyte-expressed yes-associated protein is a key activator of the early zygotic genome in mouse

    PubMed Central

    Yu, Chao; Ji, Shu-Yan; Dang, Yu-Jiao; Sha, Qian-Qian; Yuan, Yi-Feng; Zhou, Jian-Jie; Yan, Li-Ying; Qiao, Jie; Tang, Fuchou; Fan, Heng-Yu

    2016-01-01

    In early mammalian embryos, the genome is transcriptionally quiescent until the zygotic genome activation (ZGA) which occurs 2-3 days after fertilization. Despite a long-standing effort, maternal transcription factors regulating this crucial developmental event remain largely elusive. Here, using maternal and paternal mouse models of Yap1 deletion, we show that maternally accumulated yes-associated protein (YAP) in oocyte is essential for ZGA. Maternal Yap1-knockout embryos exhibit a prolonged two-cell stage and develop into the four-cell stage at a much slower pace than the wild-type controls. Transcriptome analyses identify YAP target genes in early blastomeres; two of which, Rpl13 and Rrm2, are required to mediate maternal YAP's effect in conferring developmental competence on preimplantation embryos. Furthermore, the physiological YAP activator, lysophosphatidic acid, can substantially improve early development of wild-type, but not maternal Yap1-knockout embryos in both oviduct and culture. These observations provide insights into the mechanisms of ZGA, and suggest potentials of YAP activators in improving the developmental competence of cultured embryos in assisted human reproduction and animal biotechnology. PMID:26902285

  1. Oocyte-expressed yes-associated protein is a key activator of the early zygotic genome in mouse.

    PubMed

    Yu, Chao; Ji, Shu-Yan; Dang, Yu-Jiao; Sha, Qian-Qian; Yuan, Yi-Feng; Zhou, Jian-Jie; Yan, Li-Ying; Qiao, Jie; Tang, Fuchou; Fan, Heng-Yu

    2016-03-01

    In early mammalian embryos, the genome is transcriptionally quiescent until the zygotic genome activation (ZGA) which occurs 2-3 days after fertilization. Despite a long-standing effort, maternal transcription factors regulating this crucial developmental event remain largely elusive. Here, using maternal and paternal mouse models of Yap1 deletion, we show that maternally accumulated yes-associated protein (YAP) in oocyte is essential for ZGA. Maternal Yap1-knockout embryos exhibit a prolonged two-cell stage and develop into the four-cell stage at a much slower pace than the wild-type controls. Transcriptome analyses identify YAP target genes in early blastomeres; two of which, Rpl13 and Rrm2, are required to mediate maternal YAP's effect in conferring developmental competence on preimplantation embryos. Furthermore, the physiological YAP activator, lysophosphatidic acid, can substantially improve early development of wild-type, but not maternal Yap1-knockout embryos in both oviduct and culture. These observations provide insights into the mechanisms of ZGA, and suggest potentials of YAP activators in improving the developmental competence of cultured embryos in assisted human reproduction and animal biotechnology.

  2. Improving the quality of emergency department documentation using the voice-activated word processor: interim results.

    PubMed Central

    Linn, N. A.; Rubenstein, R. M.; Bowler, A. E.; Dixon, J. L.

    1992-01-01

    We examined whether voice-activated word processors provide an acceptable means for emergency physicians to create medical records. Our study addressed three areas of inquiry: whether physicians can be induced to try this new technology, whether they will continue to use it after outside technical support is withdrawn, and the factors contributing to adoption and substantial use of voice-activated computers by practicing emergency physicians. This paper presents findings from the first half of the study, reflecting physicians' reported experiences while receiving onsite training followed by technical support for three months after system installation. Based on preliminary assessments, the keys to successful use appear to include physician and group commitment, acceptance of a steep learning curve, and flexibility in adapting the computer software and/or practice habits. PMID:1482976

  3. Extracting regulator activity profiles by integration of de novo motifs and expression data: characterizing key regulators of nutrient depletion responses in Streptomyces coelicolor

    PubMed Central

    Iqbal, Mudassar; Mast, Yvonne; Amin, Rafat; Hodgson, David A.; Wohlleben, Wolfgang; Burroughs, Nigel J.

    2012-01-01

    Determining transcriptional regulator activities is a major focus of systems biology, providing key insight into regulatory mechanisms and co-regulators. For organisms such as Escherichia coli, transcriptional regulator binding site data can be integrated with expression data to infer transcriptional regulator activities. However, for most organisms there is only sparse data on their transcriptional regulators, while their associated binding motifs are largely unknown. Here, we address the challenge of inferring activities of unknown regulators by generating de novo (binding) motifs and integrating with expression data. We identify a number of key regulators active in the metabolic switch, including PhoP with its associated directed repeat PHO box, candidate motifs for two SARPs, a CRP family regulator, an iron response regulator and that for LexA. Experimental validation for some of our predictions was obtained using gel-shift assays. Our analysis is applicable to any organism for which there is a reasonable amount of complementary expression data and for which motifs (either over represented or evolutionary conserved) can be identified in the genome. PMID:22406834

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

    PubMed Central

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

    2013-01-01

    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 μg/ 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 α-smooth muscle actin, transforming growth factor-β1, PDGF-Rβ, pro-inflammatory cytokines and enhanced expression of tissue inhibitor of metalloproteinase-1 and pro (α) 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. PMID:21134390

  5. 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.

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

    PubMed

    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 μg/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 α-smooth muscle actin, transforming growth factor-β1, PDGF-Rβ, pro-inflammatory cytokines and enhanced expression of tissue inhibitor of metalloproteinase-1 and pro(α) 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.

  7. Observing large-scale solar surface flows with GONG: Investigation of a key element in solar activity buildup

    NASA Technical Reports Server (NTRS)

    Beck, John G.; Simon, George W.; Hathaway, David H.

    1996-01-01

    The Global Oscillation Network Group (GONG) solar telescope network has begun regular operations, and will provide continuous Doppler images of large-scale nearly-steady motions at the solar surface, primarily those due to supergranulation. Not only the Sun's well-known magnetic network, but also flux diffusion, dispersal, and concentration at the surface appear to be controlled by supergranulation. Through such magnetoconvective interactions, magnetic stresses develop, leading to solar activity. We show a Doppler movie made from a 45.5 hr time series obtained 1995 May 9-10 using data from three of the six GONG sites (Learmonth, Tenerife, Tucson), to demonstrate the capability of this system.

  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. 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. PMID:27497348

  10. 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.

  11. 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.

  12. 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. PMID:26896315

  13. 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

  14. Key Beliefs for Targeted Interventions to Increase Physical Activity in Children: Analyzing Data from an Extended Version of the Theory of Planned Behaviour

    PubMed Central

    Bélanger-Gravel, A.; Godin, G.

    2010-01-01

    Given the high prevalence of overweight and low levels of physical activity among children, a better understanding of physical activity behaviour is an important step in intervention planning. This study, based on the theory of planned behaviour, was conducted among 313 fifth graders and their parents. Children completed a computer-based questionnaire to evaluate theoretical constructs and behaviour. Additional information was obtained from parents by means of a questionnaire. Correlates of children's physical activity were intention and self-identity. Determinants of intention were self-efficacy, self-identity, and attitude. Parental variables were mediated through cognitions. Among girls, practicing sedentary activities was an additional negative determinant of intention. Key beliefs of boys and girls were related to time management and difficulties associated with physical activity. For girls, social identification as an active girl was another important belief related to positive intention. This study provides theory-based information for the development of more effective interventions aimed at promoting physical activity among children. PMID:20652005

  15. 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.

  16. 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. PMID

  17. 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. PMID:26041271

  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. 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.

  20. 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.

  1. 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

  2. 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.

  3. Oscillatory phase modulates the timing of neuronal activations and resulting behavior.

    PubMed

    Coon, W G; Gunduz, A; Brunner, P; Ritaccio, A L; Pesaran, B; Schalk, G

    2016-06-01

    Human behavioral response timing is highly variable from trial to trial. While it is generally understood that behavioral variability must be due to trial-by-trial variations in brain function, it is still largely unknown which physiological mechanisms govern the timing of neural activity as it travels through networks of neuronal populations, and how variations in the timing of neural activity relate to variations in the timing of behavior. In our study, we submitted recordings from the cortical surface to novel analytic techniques to chart the trajectory of neuronal population activity across the human cortex in single trials, and found joint modulation of the timing of this activity and of consequent behavior by neuronal oscillations in the alpha band (8-12Hz). Specifically, we established that the onset of population activity tends to occur during the trough of oscillatory activity, and that deviations from this preferred relationship are related to changes in the timing of population activity and the speed of the resulting behavioral response. These results indicate that neuronal activity incurs variable delays as it propagates across neuronal populations, and that the duration of each delay is a function of the instantaneous phase of oscillatory activity. We conclude that the results presented in this paper are supportive of a general model for variability in the effective speed of information transmission in the human brain and for variability in the timing of human behavior. PMID:26975551

  4. Vertebrate opsins belonging to different classes vary in constitutively active properties resulting from salt-bridge mutations.

    PubMed

    Nickle, Benjamin; Wilkie, Susan E; Cowing, Jill A; Hunt, David M; Robinson, Phyllis R

    2006-06-13

    Vertebrate opsins are classified into one of five classes on the basis of amino acid similarity. These classes are short wavelength sensitive 1 and 2 (SWS1, SWS2), medium/long wavelength sensitive (M/LWS), and rod opsin like 1 and 2 (RH1, RH2). In bovine rod opsin (RH1), two critical amino acids form a salt bridge in the apoprotein that maintains the opsin in an inactive state. These residues are K296, which functions as the chromophore binding site, and E113, which functions as the counterion to the protonated Schiff base. Corresponding residues in each of the other vertebrate opsin classes are believed to play similar roles. Previous reports have demonstrated that mutations in these critical residues result in constitutive activation of transducin by RH1 class opsins in the absence of chromophore. Additionally, recent reports have shown that an E113Q mutation in SWS1 opsin is constitutively active. Here we ask if the other classes of vertebrate opsins maintain activation characteristics similar to that of bovine RH1 opsin. We approach this question by making the corresponding substitutions which disrupt the K296/E113 salt bridge in opsins belonging to the other vertebrate opsin classes. The mutant opsins are tested for their ability to constitutively activate bovine transducin. We demonstrate that mutations disrupting this key salt bridge produce constitutive activation in all classes. However, the mutant opsins differ in their ability to be quenched in the dark state by the addition of chromophore as well as in their level of constitutive activation. The differences in constitutive activation profiles suggest that structural differences exist among the opsin classes that may translate into a difference in activation properties.

  5. Activities Contributing to Total Energy Expenditure in the United States: Results from the NHAPS Study

    PubMed Central

    Dong, Linda; Block, Gladys; Mandel, Shelly

    2004-01-01

    Background Physical activity is increasingly recognized as an important factor influencing health and disease status. Total energy expenditure, both low-intensity and high-intensity, contributes to maintenance of healthy body weight. This paper presents the results of a quantitative approach to determining the activities that contribute to total energy expenditure in the United States. Methods Data from the National Human Activity Pattern Survey (NHAPS) were used. In 1992–1994 the NHAPS sampled 4,185 females and 3,330 males, aged 18 years and over, weighted to be representative of the 48 contiguous United States. A detailed report of each activity performed in the previous 24 hours was obtained. A score was created for each activity, by multiplying duration and intensity for each individual and summing across individuals. This score was then used to rank each activity according to its contribution to total population energy expenditure, for the total sample and separately for each gender, race, age, region, and season. Results This analysis reveals our society to be primarily sedentary; leisure time physical activity contributed only approximately 5% of the population's total energy expenditure. Not counting sleeping, the largest contributor to energy expenditure was "Driving a car", followed by "Office work" and "Watching TV". Household activities accounted for 20.1% and 33.3% of energy expenditure for males and females respectively. Conclusion The information presented in this paper may be useful in identifying common activities that could be appropriate targets for behavioral interventions to increase physical activity. PMID:15169563

  6. Active Learning in Large Classes: Can Small Interventions Produce Greater Results than Are Statistically Predictable?

    ERIC Educational Resources Information Center

    Adrian, Lynne M.

    2010-01-01

    Six online postings and six one-minute papers were added to an introductory first-year class, forming 5 percent of the final grade, but represented significant intervention in class functioning and amount of active learning. Active learning produced results in student performance beyond the percentage of the final grade it constituted. (Contains 1…

  7. 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…

  8. The p38α mitogen-activated protein kinase is a key regulator of myelination and remyelination in the CNS.

    PubMed

    Chung, S-H; Biswas, S; Selvaraj, V; Liu, X-B; Sohn, J; Jiang, P; Chen, C; Chmilewsky, F; Marzban, H; Horiuchi, M; Pleasure, D E; Deng, W

    2015-05-07

    The p38α mitogen-activated protein kinase (MAPK) is one of the serine/threonine kinases regulating a variety of biological processes, including cell-type specification, differentiation and migration. Previous in vitro studies using pharmacological inhibitors suggested that p38 MAPK is essential for oligodendrocyte (OL) differentiation and myelination. To investigate the specific roles of p38α MAPK in OL development and myelination in vivo, we generated p38α conditional knockout (CKO) mice under the PLP and nerve/glial antigen 2 (NG2) gene promoters, as these genes are specifically expressed in OL progenitor cells (OPCs). Our data revealed that myelin synthesis was completely inhibited in OLs differentiated from primary OPC cultures derived from the NG2 Cre-p38α CKO mouse brains. Although an in vivo myelination defect was not obvious after gross examination of these mice, electron microscopic analysis showed that the ultrastructure of myelin bundles was severely impaired. Moreover, the onset of myelination in the corpus callosum was delayed in the knockout mice compared with p38α fl/fl control mice. A delay in OL differentiation in the central nervous system was observed with concomitant downregulation in the expression of OPC- and OL-specific genes such as Olig1 and Zfp488 during early postnatal development. OPC proliferation was not affected during this time. These data indicate that p38α is a positive regulator of OL differentiation and myelination. Unexpectedly, we observed an opposite effect of p38α on remyelination in the cuprizone-induced demyelination model. The p38α CKO mice exhibited better remyelination capability compared with p38α fl/fl mice following demyelination. The opposing roles of p38α in myelination and remyelination could be due to a strong anti-inflammatory effect of p38α or a dual reciprocal regulatory action of p38α on myelin formation during development and on remyelination after demyelination.

  9. 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…

  10. 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…

  11. 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…

  12. 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…

  13. 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

  14. The Hubble Space Telescope Quasar Absorption Line Key Project. 10: Galactic H I 21 centimeter emission toward 143 quasars and active Galactic nuclei

    NASA Technical Reports Server (NTRS)

    Lockman, Felix J.; Savage, Blair D.

    1995-01-01

    Sensitive H I 21 cm emission line spectra have been measured for the directions to 143 quasars and active galactic nuclei (AGNs) chosen from the observing lists for the Hubble Space Telescope (HST) Quasar Absorption Line Key Project. Narrow-band and wide-band data were obtained with the National Radio Astronomy Observatory (NRAO) 43 m radio telescope for each object. The narrow-band data have a velocity resolution of 1 km/s, extend from -220 to +170 km/s, and are corrected for stray 21 cm radiation. The wide-band data have a resolution of 4 km/s and extend from -1000 to +1000 km/s. The data are important for the interpretation of ultraviolet absorption lines near zero redshift in Key Project spectra. Twenty-two percent of the quasars lie behind Galactic high-velocity H I clouds with absolute value of V(sub LSR) greater than 100 km/s whose presence can increase the equivalent width of interstellar absorption lines significantly. This paper contains the emission spectra and measures of the H I velocities and column densities along the sight line to each quasar. We discuss how the measurements can be used to estimate the visual and ultraviolet extinction toward each quasar and to predict the approximate strength of the strong ultraviolet resonance lines of neutral gas species in the HST Key Project spectra.

  15. 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.

  16. 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.

  17. 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.

  18. Exploration of the key microbes involved in the cellulolytic activity of a microbial consortium by serial dilution.

    PubMed

    Zhang, Qinghua; Tian, Min; Tang, Lei; Li, Huixing; Li, Wencheng; Zhang, Jianhua; Zhang, Hongjian; Mao, Zhonggui

    2013-03-01

    A highly cellulolytic consortium was serially diluted and incubated in fermentation medium with filter paper as carbon sources. The critical dilution point of the consortium for effective degradation of filter paper was 10(-5) as further dilution resulted in the loss of degradation ability of filter paper accompanied by the disappearance of four bands in denaturing gradient gel electrophoresis profiles. The loss of bands corresponding to 16S rRNA sequences from Clostridium clariflavum DSM 19732 and a Paenibacillus species coincided with the loss of degradation ability of filter paper.

  19. 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

  20. 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…

  1. Escherichia coli purine repressor: key residues for the allosteric transition between active and inactive conformations and for interdomain signaling.

    PubMed

    Lu, F; Brennan, R G; Zalkin, H

    1998-11-10

    The Escherichia coli purine repressor, PurR, exists in an equilibrium between open and closed conformations. Binding of a corepressor, hypoxanthine or guanine, shifts the allosteric equilibrium in favor of the closed conformation and increases the operator DNA binding affinity by 40-fold compared to aporepressor. Glu70 and Trp147 PurR mutations were isolated which perturb the allosteric equilibrium. Three lines of evidence indicate that the allosteric equilibrium of E70A and W147A aporepressors was shifted toward the closed conformation. First, compared to wild-type PurR, these mutant repressors had a 10-30-fold higher corepressor binding affinity. Second, the mutant aporepressors bound to operator DNA with an affinity that is characteristic of the wild-type PurR holorepressor. Third, binding of guanine to wild-type PurR resulted in a near-UV circular dichroism spectral change at 297-305 nm that is attributed to the closed conformation. The circular dichroism spectrum of the E70A aporepressor at 297-305 nm was that expected for the closed conformation, and it was not appreciably altered by corepressor binding. Mutational analysis was used to identify an Arg115-Ser46' interdomain intersubunit hydrogen bond that is necessary for transmitting the allosteric transition in the corepressor binding domain to the DNA binding domain. R115A and S46G PurR mutants were defective in DNA binding in vitro and repressor function in vivo although corepressor binding was identical to the wild type. These results establish that the hydrogen bond between the side chain NH2 of Arg115 and the main chain CO of Ser46' plays a critical role in interdomain signaling.

  2. Preliminary results from a study of the impact of digital activity trackers on health risk status.

    PubMed

    Rowe-Roberts, Dinah; Cercos, Robert; Mueller, Florian 'Floyd'

    2014-01-01

    Digital activity trackers are becoming increasingly more widespread and affordable, providing new opportunities to support participatory e-health programs in which participants take an active role. However, there is limited knowledge of how to deploy these activity trackers within these programs. In response, we conducted a 7-month study with 212 employees using a wireless activity tracker to log step count. Our results suggest that these devices can support improving physical activity levels and consequently reduce diabetes risk factors. Furthermore, the intervention seems more effective for people with higher risk factors. With our work we aim to contribute to a better understanding of the issues and challenges involved in the design of participatory e-health programs that include activity trackers. PMID:25087541

  3. Disruption of SF3B1 results in deregulated expression and splicing of key genes and pathways in myelodysplastic syndrome hematopoietic stem and progenitor cells.

    PubMed

    Dolatshad, H; Pellagatti, A; Fernandez-Mercado, M; Yip, B H; Malcovati, L; Attwood, M; Przychodzen, B; Sahgal, N; Kanapin, A A; Lockstone, H; Scifo, L; Vandenberghe, P; Papaemmanuil, E; Smith, C W J; Campbell, P J; Ogawa, S; Maciejewski, J P; Cazzola, M; Savage, K I; Boultwood, J

    2015-05-01

    The splicing factor SF3B1 is the most commonly mutated gene in the myelodysplastic syndrome (MDS), particularly in patients with refractory anemia with ring sideroblasts (RARS). We investigated the functional effects of SF3B1 disruption in myeloid cell lines: SF3B1 knockdown resulted in growth inhibition, cell cycle arrest and impaired erythroid differentiation and deregulation of many genes and pathways, including cell cycle regulation and RNA processing. MDS is a disorder of the hematopoietic stem cell and we thus studied the transcriptome of CD34(+) cells from MDS patients with SF3B1 mutations using RNA sequencing. Genes significantly differentially expressed at the transcript and/or exon level in SF3B1 mutant compared with wild-type cases include genes that are involved in MDS pathogenesis (ASXL1 and CBL), iron homeostasis and mitochondrial metabolism (ALAS2, ABCB7 and SLC25A37) and RNA splicing/processing (PRPF8 and HNRNPD). Many genes regulated by a DNA damage-induced BRCA1-BCLAF1-SF3B1 protein complex showed differential expression/splicing in SF3B1 mutant cases. This is the first study to determine the target genes of SF3B1 mutation in MDS CD34(+) cells. Our data indicate that SF3B1 has a critical role in MDS by affecting the expression and splicing of genes involved in specific cellular processes/pathways, many of which are relevant to the known RARS pathophysiology, suggesting a causal link.

  4. Disruption of SF3B1 results in deregulated expression and splicing of key genes and pathways in myelodysplastic syndrome hematopoietic stem and progenitor cells

    PubMed Central

    Dolatshad, H; Pellagatti, A; Fernandez-Mercado, M; Yip, B H; Malcovati, L; Attwood, M; Przychodzen, B; Sahgal, N; Kanapin, A A; Lockstone, H; Scifo, L; Vandenberghe, P; Papaemmanuil, E; Smith, C W J; Campbell, P J; Ogawa, S; Maciejewski, J P; Cazzola, M; Savage, K I; Boultwood, J

    2015-01-01

    The splicing factor SF3B1 is the most commonly mutated gene in the myelodysplastic syndrome (MDS), particularly in patients with refractory anemia with ring sideroblasts (RARS). We investigated the functional effects of SF3B1 disruption in myeloid cell lines: SF3B1 knockdown resulted in growth inhibition, cell cycle arrest and impaired erythroid differentiation and deregulation of many genes and pathways, including cell cycle regulation and RNA processing. MDS is a disorder of the hematopoietic stem cell and we thus studied the transcriptome of CD34+ cells from MDS patients with SF3B1 mutations using RNA sequencing. Genes significantly differentially expressed at the transcript and/or exon level in SF3B1 mutant compared with wild-type cases include genes that are involved in MDS pathogenesis (ASXL1 and CBL), iron homeostasis and mitochondrial metabolism (ALAS2, ABCB7 and SLC25A37) and RNA splicing/processing (PRPF8 and HNRNPD). Many genes regulated by a DNA damage-induced BRCA1–BCLAF1–SF3B1 protein complex showed differential expression/splicing in SF3B1 mutant cases. This is the first study to determine the target genes of SF3B1 mutation in MDS CD34+ cells. Our data indicate that SF3B1 has a critical role in MDS by affecting the expression and splicing of genes involved in specific cellular processes/pathways, many of which are relevant to the known RARS pathophysiology, suggesting a causal link. PMID:25428262

  5. Subliminal psychodynamic activation: updated comprehensive list of experimental results and comments on previous lists.

    PubMed

    Fudin, R; Benjamin, C

    1992-06-01

    A comprehensive list of results from visual subliminal psychodynamic activation experiments is presented. This list includes results reported since the publication of the last comprehensive list by Weinberger and Hardaway in 1990 and several results not found on that list. On the present list, SPA results are categorized according to criteria that we contend are more objective than those used previously. In contrast to conclusions drawn from previous lists prepared by Silverman in 1980 and 1983, by Weinberger and Hardaway in 1990, and by Weinberger and Silverman in 1987, the present list indicates that the results of a majority of experiments do not clearly support hypotheses tested by the subliminal psychodynamic activation method. Aspects of Hardaway's meta-analyses from 1987 and 1990 for major areas of research on subliminal psychodynamic activation are discussed in terms of suggestions for further research. PMID:1608734

  6. Comparative studies on the inhibitory activities of selected benzoic acid derivatives against secretory phospholipase A2, a key enzyme involved in the inflammatory pathway.

    PubMed

    Dileep, K V; Remya, C; Cerezo, J; Fassihi, A; Pérez-Sánchez, H; Sadasivan, C

    2015-07-01

    Inflammation is considered to be a key factor in major diseases like cancer, Alzheimer's disease, Parkinson's disease, etc. For the past few decades, pharmaceutical companies have explored new effective medications against inflammation. As a part of their detailed studies, many drug targets and drugs have been introduced against inflammation. In the present study, the inhibiting capacities of selected benzoic acid derivatives like gallic acid, vannilic acid, syringic acid and protocatechuic acid against secretory phospholipase A2 (sPLA2), a major enzyme involved in the inflammatory pathway, have been investigated. The detailed in vitro, biophysical and in silico studies carried out on these benzoic acid derivatives revealed that all the selected compounds have a uniform mode of binding in the active site of sPLA2 and are inhibitory in micromolar concentrations. The study also focuses on the non-selective inhibitory activity of an NSAID, aspirin, against sPLA2.

  7. Effects of the activities of key enzymes involved in starch biosynthesis on the fine structure of amylopectin in developing rice (Oryza sativa L.) endosperms.

    PubMed

    Lü, Bing; Guo, ZhiGang; Liang, JianSheng

    2008-10-01

    The dynamic changes of the activities of enzymes involving in starch biosynthesis, including ADP-glucose pyrophosphorylase (AGPase), soluble starch synthases (SSS), starch branching enzyme (SBE) and starch debranching enzymes (DBE) were studied, and changes of fine structure of amylopectin were characterized by isoamylase treatment during rice grain development, using trans anti-waxy gene rice plants. The relationships between the activities of those key enzymes were also analyzed. The amylose synthesis was significantly inhibited in transgenic Wanjing 9522, but the total starch content and final grain weight were less affected as compared with those of non-transgenic Wanjing 9522 rice cultivar. Analyses on the changes of activities of enzymes involving in starch biosynthesis showed that different enzyme activities were expressed differently during rice endosperm development. Soluble starch synthase is relatively highly expressed in earlier stage of endosperm development, whilst maximal expression of granule-bound starch synthase (GBSS) occurred in mid-stage of endosperm development. No obvious differences in changes of the activities of AGPase and SBE between two rice cultivars investigated, except the DBEs. Distribution patterns of branches of amylopectin changed continually during the development of rice grains and varied between two rice cultivars. It was suggested that amylopectin synthesis be prior to the synthesis of amylose and different enzymes have different roles in controlling syntheses of branches of amylopectin.

  8. Vitiligo-inducing phenols activate the unfolded protein response in melanocytes resulting in upregulation of IL6 and IL8.

    PubMed

    Toosi, Siavash; Orlow, Seth J; Manga, Prashiela

    2012-11-01

    Vitiligo is characterized by depigmented skin patches caused by loss of epidermal melanocytes. Oxidative stress may have a role in vitiligo onset, while autoimmunity contributes to disease progression. In this study, we sought to identify mechanisms that link disease triggers and spreading of lesions. A hallmark of melanocytes at the periphery of vitiligo lesions is dilation of the endoplasmic reticulum (ER). We hypothesized that oxidative stress results in redox disruptions that extend to the ER, causing accumulation of misfolded peptides, which activates the unfolded protein response (UPR). We used 4-tertiary butyl phenol and monobenzyl ether of hydroquinone, known triggers of vitiligo. We show that expression of key UPR components, including the transcription factor X-box-binding protein 1 (XBP1), is increased following exposure of melanocytes to phenols. XBP1 activation increases production of immune mediators IL6 and IL8. Co-treatment with XBP1 inhibitors reduced IL6 and IL8 production induced by phenols, while overexpression of XBP1 alone increased their expression. Thus, melanocytes themselves produce cytokines associated with activation of an immune response following exposure to chemical triggers of vitiligo. These results expand our understanding of the mechanisms underlying melanocyte loss in vitiligo and pathways linking environmental stressors and autoimmunity.

  9. β-Eliminative depolymerization of the fucosylated chondroitin sulfate and anticoagulant activities of resulting fragments.

    PubMed

    Gao, Na; Lu, Feng; Xiao, Chuang; Yang, Lian; Chen, Jun; Zhou, Kai; Wen, Dandan; Li, Zi; Wu, Mingyi; Jiang, Jianmin; Liu, Guangming; Zhao, Jinhua

    2015-01-01

    Fucosylated chondroitin sulfate (FCS) from sea cucumber with complex structure has potent anticoagulant activity by inhibition of intrinsic tenase; however, it could activate factor XII and platelet. To obtain FCS' fragments with selective inhibition on intrinsic tenase, a method for β-eliminative depolymerization of FCS was developed by treating FCS benzyl esters with alkaline in anhydrous solution. Our results demonstrated that the glycosidic linkages of GalNAc-β1, 4-GlcA were selectively cleaved and distinctive Δ(4,5) unsaturated hexuronic acid was formed at non-reducing end of resulting fragments, while the main structures were essentially stable during depolymerization. By this method, five depolymerized fragments (dFCSs) with various molecular sizes were prepared and their anticoagulant activities and activation activities of factor XII and platelet were compared. Overall, dFCSs with Mw 3.2-8.8 kDa reserved potent anticoagulant activities by inhibition of intrinsic tenase, and activation activities of factor XII or platelet could be diminished or eliminated.

  10. 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

  11. 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)

  12. The virion host shutoff RNase plays a key role in blocking the activation of protein kinase R in cells infected with herpes simplex virus 1.

    PubMed

    Sciortino, Maria Teresa; Parisi, Tiziana; Siracusano, Gabriel; Mastino, Antonio; Taddeo, Brunella; Roizman, Bernard

    2013-03-01

    Earlier studies have shown that active MEK blocks the activation of protein kinase R (PKR), a component of antiviral innate immune responses. In this report we show that the herpes simplex virus 1 virion host shutoff (VHS) RNase protein and MEK (mitogen-activated protein kinase kinase) act cooperatively in blocking the activation of PKR. This conclusion is based on the following. (i) In contrast to viral gene expression in the parental cell line or a cell line expressing a constitutively active MEK, the replication of a VHS mutant is particularly impaired in cells expressing dominant negative MEK. In this cell line PKR is activated by phosphorylation, and the accumulation of several viral proteins is delayed. (ii) In transfected cells, wild-type VHS blocked the activation of PKR, whereas PKR was activated in cells transfected with a mutant VHS or with plasmids encoding the VHS RNase and VP16 and VP22, the two viral proteins that neutralize the RNase activity of VHS. The results suggest that early in infection the VHS RNase degrades RNAs that activate PKR. Coupled with published data, the results suggest that inhibition of activation of PKR or its effect on viral replication is staged early in infection by VHS, postsynthesis of VP16 and VP22 by the γ(1)34.5 protein, and very late in infection by the U(S)11 protein.

  13. 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…

  14. Scanning L-Band Active Passive (SLAP) - Recent Results from an Airborne Simulator for SMAP

    NASA Technical Reports Server (NTRS)

    Kim, Edward

    2015-01-01

    Scanning L-band Active Passive (SLAP) is a recently-developed NASA airborne instrument specially tailored to simulate the new Soil Moisture Active Passive (SMAP) satellite instrument suite. SLAP conducted its first test flights in December, 2013 and participated in its first science campaign-the IPHEX ground validation campaign of the GPM mission-in May, 2014. This paper will present results from additional test flights and science observations scheduled for 2015.

  15. 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.

  16. Does pedometer goal setting improve physical activity among Native elders? Results from a randomized pilot study.

    PubMed

    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 between-group differences were found, within-group analyses indicated that elders significantly improved on the majority of step count, physical activity, health-related quality of life, and 6-minute walk outcomes.

  17. Cutting Edge: RIP1 kinase activity is dispensable for normal development but is a key regulator of inflammation in SHARPIN-deficient mice.

    PubMed

    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

    2014-06-15

    RIP1 (RIPK1) kinase is a key regulator of TNF-induced NF-κB 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. In this study, we generated RIP1 kinase-dead (Ripk1(K45A)) mice and showed they are viable and healthy, indicating that the kinase activity of RIP1, but not its scaffolding function, is dispensable for viability and homeostasis. After validating that the Ripk1(K45A) mice were specifically protected against necroptotic stimuli in vitro and in vivo, we crossed them with SHARPIN-deficient cpdm mice, which develop severe skin and multiorgan inflammation that has been hypothesized to be mediated by TNF-dependent apoptosis and/or necroptosis. Remarkably, crossing Ripk1(K45A) mice with 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.

  18. 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

  19. Early activation of caspases during T lymphocyte stimulation results in selective substrate cleavage in nonapoptotic cells.

    PubMed

    Alam, A; Cohen, L Y; Aouad, S; Sékaly, R P

    1999-12-20

    Apoptosis induced by T cell receptor (TCR) triggering in T lymphocytes involves activation of cysteine proteases of the caspase family through their proteolytic processing. Caspase-3 cleavage was also reported during T cell stimulation in the absence of apoptosis, although the physiological relevance of this response remains unclear. We show here that the caspase inhibitor benzyloxycarbonyl (Cbz)-Val-Ala-Asp(OMe)-fluoromethylketone (zVAD) blocks proliferation, major histocompatibility complex class II expression, and blastic transformation during stimulation of peripheral blood lymphocytes. Moreover, T cell activation triggers the selective processing and activation of downstream caspases (caspase-3, -6, and -7), but not caspase-1, -2, or -4, as demonstrated even in intact cells using a cell-permeable fluorescent substrate. Caspase-3 processing occurs in different T cell subsets (CD4(+), CD8(+), CD45RA(+), and CD45RO(+)), and in activated B lymphocytes. The pathway leading to caspase activation involves death receptors and caspase-8, which is also processed after TCR triggering, but not caspase-9, which remains as a proenzyme. Most importantly, caspase activity results in a selective substrate specificity, since poly(ADP-ribose) polymerase (PARP), lamin B, and Wee1 kinase, but not DNA fragmentation factor (DFF45) or replication factor C (RFC140), are processed. Caspase and substrate processing occur in nonapoptotic lymphocytes. Thus, caspase activation is an early and physiological response in viable, stimulated lymphocytes, and appears to be involved in early steps of lymphocyte activation. PMID:10601362

  20. NKG2D is a Key Receptor for Recognition of Bladder Cancer Cells by IL-2-Activated NK Cells and BCG Promotes NK Cell Activation

    PubMed Central

    García-Cuesta, Eva María; López-Cobo, Sheila; Álvarez-Maestro, Mario; Esteso, Gloria; Romera-Cárdenas, Gema; Rey, Mercedes; Cassady-Cain, Robin L.; Linares, Ana; Valés-Gómez, Alejandro; Reyburn, Hugh Thomson; Martínez-Piñeiro, Luis; Valés-Gómez, Mar

    2015-01-01

    Intravesical instillation of bacillus Calmette–Guérin (BCG) is used to treat superficial bladder cancer, either papillary tumors (after transurethral resection) or high-grade flat carcinomas (carcinoma in situ), reducing recurrence in about 70% of patients. Initially, BCG was proposed to work through an inflammatory response, mediated by phagocytic uptake of mycobacterial antigens and cytokine release. More recently, other immune effectors such as monocytes, natural killer (NK), and NKT cells have been suggested to play a role in this immune response. Here, we provide a comprehensive study of multiple bladder cancer cell lines as putative targets for immune cells and evaluated their recognition by NK cells in the presence and absence of BCG. We describe that different bladder cancer cells can express multiple activating and inhibitory ligands for NK cells. Recognition of bladder cancer cells depended mainly on NKG2D, with a contribution from NKp46. Surprisingly, exposure to BCG did not affect the immune phenotype of bladder cells nor increased NK cell recognition of purified IL-2-activated cell lines. However, NK cells were activated efficiently when BCG was included in mixed lymphocyte cultures, suggesting that NK activation after mycobacteria treatment requires the collaboration of various immune cells. We also analyzed the percentage of NK cells in peripheral blood of a cohort of bladder cancer patients treated with BCG. The total numbers of NK cells did not vary during treatment, indicating that a more detailed study of NK cell activation in the tumor site will be required to evaluate the response in each patient. PMID:26106390

  1. Aluminum-induced decrease in CO2 assimilation in citrus seedlings is unaccompanied by decreased activities of key enzymes involved in CO2 assimilation.

    PubMed

    Chen, Li-Song; Qi, Yi-Ping; Smith, Brandon Rhett; Liu, Xing-Hui

    2005-03-01

    'Cleopatra' tangerine (Citrus reshni Hort. ex Tanaka) seedlings were irrigated daily for 8 weeks with 1/4 strength Hoagland's nutrient solution containing 0 (control) or 2 mM aluminum (Al). Leaves from Al-treated plants had decreased CO2 assimilation and stomatal conductance, but increased intercellular CO2 concentrations compared with control leaves. On a leaf area basis, 2 mM Al increased activities of key enzymes in the Calvin cycle, including ribulose-1,5-bisphosphate carboxylase/oxygenase (Rubisco), NADP-glyceraldehyde-3-phosphate dehydrogenase (GAPDH), phosphoribulokinase (PRK), stromal fructose-1,6-bisphosphatase (FBPase), and a key enzyme in starch synthesis, ADP-glucose pyrophosphorylase (AGPase), compared with control leaves. Aluminum had no effect on cytosolic FBPase activity, but it decreased sucrose phosphate synthase (SPS) activity. Aluminum had no effect on area-based concentrations of carbohydrates, glucose-6-phosphate (G6P) and fructose 6-phosphate (F6P) or the G6P:F6P ratio, but it decreased the area-based concentration of 3-phosphoglycerate (PGA). Photochemical quenching coefficient (qP) and electron transport rate through PSII were greatly reduced by Al. Non-photochemical quenching coefficient (NPQ) was less affected by Al than qP and electron transport rate through PSII. We conclude that the reduced rate of CO2 assimilation in Al-treated leaves was probably caused by a combination of factors such as reduced electron transport rate through PSII, increased closure of PSII reaction centers and increased photorespiration.

  2. 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.

  3. Brain activation patterns resulting from learning letter forms through active self-production and passive observation in young children

    PubMed Central

    Kersey, Alyssa J.; James, Karin H.

    2013-01-01

    Although previous literature suggests that writing practice facilitates neural specialization for letters, it is unclear if this facilitation is driven by the perceptual feedback from the act of writing or the actual execution of the motor act. The present study addresses this issue by measuring the change in BOLD signal in response to hand-printed letters, unlearned cursive letters, and cursive letters that 7-year-old children learned actively, by writing, and passively, by observing an experimenter write. Brain activation was assessed using fMRI while perceiving letters—in both cursive and manuscript forms. Results showed that active training led to increased recruitment of the sensori-motor network associated with letter perception as well as the insula and claustrum, but passive observation did not. This suggests that perceptual networks for newly learned cursive letters are driven by motor execution rather than by perceptual feedback. PMID:24069007

  4. Brain activation patterns resulting from learning letter forms through active self-production and passive observation in young children.

    PubMed

    Kersey, Alyssa J; James, Karin H

    2013-01-01

    Although previous literature suggests that writing practice facilitates neural specialization for letters, it is unclear if this facilitation is driven by the perceptual feedback from the act of writing or the actual execution of the motor act. The present study addresses this issue by measuring the change in BOLD signal in response to hand-printed letters, unlearned cursive letters, and cursive letters that 7-year-old children learned actively, by writing, and passively, by observing an experimenter write. Brain activation was assessed using fMRI while perceiving letters-in both cursive and manuscript forms. Results showed that active training led to increased recruitment of the sensori-motor network associated with letter perception as well as the insula and claustrum, but passive observation did not. This suggests that perceptual networks for newly learned cursive letters are driven by motor execution rather than by perceptual feedback.

  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. Deriving rules from activity diary data: A learning algorithm and results of computer experiments

    NASA Astrophysics Data System (ADS)

    Arentze, Theo A.; Hofman, Frank; Timmermans, Harry J. P.

    Activity-based models consider travel as a derived demand from the activities households need to conduct in space and time. Over the last 15 years, computational or rule-based models of activity scheduling have gained increasing interest in time-geography and transportation research. This paper argues that a lack of techniques for deriving rules from empirical data hinders the further development of rule-based systems in this area. To overcome this problem, this paper develops and tests an algorithm for inductively deriving rules from activity-diary data. The decision table formalism is used to exhaustively represent the theoretically possible decision rules that individuals may use in sequencing a given set of activities. Actual activity patterns of individuals are supplied to the system as examples. In an incremental learning process, the system progressively improves on the selection of rules used for reproducing the examples. Computer experiments based on simulated data are performed to fine-tune rule selection and rule value update functions. The results suggest that the system is effective and fairly robust for parameter settings. It is concluded, therefore, that the proposed approach opens up possibilities to derive empirically tested rule-based models of activity scheduling. Follow-up research will be concerned with testing the system on empirical data.

  7. 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.

  8. 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

  9. Heparinase I-specific disaccharide unit of heparin is a key structure but insufficient for exerting anti-prion activity in prion-infected cells.

    PubMed

    Teruya, Kenta; Wakao, Masahiro; Sato, Masaki; Hamanaka, Taichi; Nishizawa, Keiko; Funayama, Yukino; Sakasegawa, Yuji; Suda, Yasuo; Doh-ura, Katsumi

    2015-05-15

    Glycosaminoglycans reportedly play important roles in prion formation, but because of their structural complexity, the chemical structures affecting prion formation have not been fully evaluated. Here, we compared two types of low molecular weight heparins and found that heparinase I-sensitive structures influenced anti-prion activity in prion-infected cells. Surface plasmon resonance analyses showed significant binding of a representative heparinase I substrate disaccharide unit, GlcNS6S-IdoA2S, to recombinant prion protein (PrP) fragments, such as full-length PrP23-231 and N-terminal domain PrP23-89, but not to PrP89-230. This binding was competitively inhibited by heparin or pentosan polysulfate, but not by Cu(2+). These PrP binding profiles of the disaccharide unit are consistent with those previously reported for heparin. However, synthetic compounds comprising disaccharide unit alone or its multimers exhibited no anti-prion activity in prion-infected cells. Consequently, the findings suggest that the heparin disaccharide unit that binds to the N-terminal region of PrP is a key structure, but it is insufficient for exerting anti-prion activity.

  10. 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

    2016-01-01

    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. PMID:27329850

  11. 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.

  12. "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)…

  13. [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.

  14. Elucidation of a key position for acyltransfer activity in Candida parapsilosis lipase/acyltransferase (CpLIP2) and in Pseudozyma antarctica lipase A (CAL-A) by rational design.

    PubMed

    Jan, Anne-Hélène; Subileau, Maeva; Deyrieux, Charlotte; Perrier, Véronique; Dubreucq, Éric

    2016-02-01

    Performing transesterifications in aqueous media is becoming a priority challenge in lipid biotechnology in order to develop more eco-friendly and efficient biocatalytic processes in systems containing both polar and apolar substrates. In this context, our group has explored for several years the high potential of the lipase/acyltransferase CpLIP2 from Candida parapsilosis and of several of its homologs, that catalyze efficiently acyltransfer reactions in lipid/water media with high water activity (aw>0.9). The discovery of a new member of this group, CduLAc from Candida dubliniensis, with a higher acyltransferase activity than CpLIP2, has provided a new insight on structure-function relationships in this group. Indeed, the comparison of sequences and 3D models, especially of CpLIP2 and CduLAc, with those of the phylogenetically related lipase A from Pseudozyma antarctica (CAL-A), allowed elucidating a key structural determinant of the acyltransferase activity: serine S369 in CpLIP2 and its equivalents E370 in CAL-A and A366 in CduLAc. Mutants obtained by rational design at this key position showed significant changes in acyltransfer activity. Whereas mutation S369E resulted in an increase in the hydrolytic activity of CpLIP2, S369A increased alcoholysis. More strikingly, the single E370A mutation in CAL-A drastically increased the acyltransferase activity of this enzyme, giving it the character of a lipase/acyltransferase. Indeed, this single mutation lowered the methanol concentration for which the initial rates of alcoholysis and hydrolysis are equal from 2M in CAL-A down to 0.3M in its mutant, while the exceptional stability of the parental enzyme toward alcohol and temperature was conserved.

  15. 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. PMID:15890680

  16. 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.

  17. Activity based financing in England: the need for continual refinement of payment by results.

    PubMed

    Street, Andrew; Maynard, Alan

    2007-10-01

    The English National Health Service is introducing activity based tariff systems or Payment by Results (PbR) as the basis for hospital funding. The funding arrangements provide incentives for increasing activity, particularly day surgery, and, uniquely, are based on costing data from all hospitals. But prices should not be based on average costs and the potential of PbR to improve the quality of care is yet to be exploited. Without refinement, PbR threatens to undermine expenditure control, to divert resources away from primary care, and to distort needs based funding. PMID:18634642

  18. 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

  19. Report of a successful ongoing pregnancy as a result of IMSI with assisted oocyte activation.

    PubMed

    Doroftei, Bogdan; Zlei, Mihaela; Simionescu, Gabriela; Maftei, Radu; Cumpata, Simona; Emerson, Geraldine

    2015-05-03

    We report a successful ongoing pregnancy obtained in a case of total globozoospermia after intracytoplasmic morphologically selected sperm injection (IMSI) with oocyte activation. The first semen analysis on investigation showed partial globozoospermia. However, under high magnification assessment at oocyte retrieval only round headed sperm were observed. Considering the high risk of a complete failure to fertilize from IMSI the couple gave written informed consent to the use of oocyte activation media post IMSI. One embryo fertilized, developed to a hatching blastocyst and was transferred resulting in an ongoing pregnancy. This successful outcome shows the use of IMSI is useful in the evaluation of total globozooozpermia and therefore aids in the justification of the use of oocyte activation media.

  20. HIV-1 Tat Protein Increases Microglial Outward K+ Current and Resultant Neurotoxic Activity

    PubMed Central

    Liu, Jianuo; Xu, Peng; Collins, Cory; Liu, Han; Zhang, Jingdong; Keblesh, James P.; Xiong, Huangui

    2013-01-01

    Microglia plays a crucial role in the pathogenesis of HIV-1-associated neurocognitive disorders. Increasing evidence indicates the voltage-gated potassium (Kv) channels are involved in the regulation of microglia function, prompting us to hypothesize Kv channels may also be involved in microglia-mediated neurotoxic activity in HIV-1-infected brain. To test this hypothesis, we investigated the involvement of Kv channels in the response of microglia to HIV-1 Tat protein. Treatment of rat microglia with HIV-1 Tat protein (200 ng/ml) resulted in pro-inflammatory microglial activation, as indicated by increases in TNF-α, IL-1β, reactive oxygen species, and nitric oxide, which were accompanied by enhanced outward K+ current and Kv1.3 channel expression. Suppression of microglial Kv1.3 channel activity, either with Kv1.3 channel blockers Margatoxin, 5-(4-Phenoxybutoxy)psoralen, or broad-spectrum K+ channel blocker 4-Aminopyridine, or by knockdown of Kv1.3 expression via transfection of microglia with Kv1.3 siRNA, was found to abrogate the neurotoxic activity of microglia resulting from HIV-1 Tat exposure. Furthermore, HIV-1 Tat-induced neuronal apoptosis was attenuated with the application of supernatant collected from K+ channel blocker-treated microglia. Lastly, the intracellular signaling pathways associated with Kv1.3 were investigated and enhancement of microglial Kv1.3 was found to correspond with an increase in Erk1/2 mitogen-activated protein kinase activation. These data suggest targeting microglial Kv1.3 channels may be a potential new avenue of therapy for inflammation-mediated neurological disorders. PMID:23738010

  1. WITNESSING THE KEY EARLY PHASE OF QUASAR EVOLUTION: AN OBSCURED ACTIVE GALACTIC NUCLEUS PAIR IN THE INTERACTING GALAXY IRAS 20210+1121

    SciTech Connect

    Piconcelli, Enrico; Fiore, Fabrizio; Maiolino, Roberto; Nicastro, Fabrizio; Vignali, Cristian; Bianchi, Stefano; Mathur, Smita; Guainazzi, Matteo; Lanzuisi, Giorgio

    2010-10-20

    We report the discovery of an active galactic nucleus (AGN) pair in the interacting galaxy system IRAS 20210+1121 at z = 0.056. An XMM-Newton observation reveals the presence of an obscured (N {sub H} {approx} 5 x 10{sup 23} cm{sup -2}), Seyfert-like (L {sub 2-10keV} = 4.7 x 10{sup 42} erg s{sup -1}) nucleus in the northern galaxy, which lacks unambiguous optical AGN signatures. Our spectral analysis also provides strong evidence that the IR-luminous southern galaxy hosts a Type 2 quasar embedded in a bright starburst emission. In particular, the X-ray primary continuum from the nucleus appears totally depressed in the XMM-Newton band as expected in the case of a Compton-thick absorber, and only the emission produced by Compton scattering ('reflection') of the continuum from circumnuclear matter is seen. As such, IRAS 20210+1121 seems to provide an excellent opportunity to witness a key, early phase in the quasar evolution predicted by the theoretical models of quasar activation by galaxy collisions.

  2. Probing the active site of MIO-dependent 2,3-aminomutases, key catalysts in the biosynthesis of beta-amino acids incorporated in secondary metabolites

    PubMed Central

    Bruner, Steven D.; Cooke, Heather

    2012-01-01

    The tyrosine aminomutase SgTAM produces (S)-β-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 α,β-unsaturated carboxylates. Studies of substrate specificity have been described for lyases but there have been no 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 α,β-unsaturated intermediates to form β-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 co-crystal 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. PMID:20577998

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Mannose-6-Phosphate Reductase, a Key Enzyme in Photoassimilate Partitioning, Is Abundant and Located in the Cytosol of Photosynthetically Active Cells of Celery (Apium graveolens L.) Source Leaves.

    PubMed

    Everard, J. D.; Franceschi, V. R.; Loescher, W. H.

    1993-06-01

    Mannitol, a major photosynthetic product and transport carbohydrate in many plants, accounts for approximately 50% of the carbon fixed by celery (Apium graveolens L.) leaves. Previous subfractionation studies of celery leaves indicated that the enzymes for mannitol synthesis were located in the cytosol, but these data are inconsistent with that published for the sites of sugar alcohol synthesis in other families and taxa, including apple (Malus) and a brown alga (Fucus). Using antibodies to a key synthetic enzyme, NADPH-dependent mannose-6-phosphate reductase (M6PR), and immunocytochemical techniques, we have resolved both the inter-cellular and intracellular sites of mannitol synthesis. In leaves, M6PR was found only in cells containing ribulose-1,5-bisphosphate carboxylase/oxygenase. M6PR was almost exclusively cytosolic in these cells, with the nucleus being the only organelle to show labeling. The key step in transport carbohydrate biosynthesis that is catalyzed by M6PR displays no apparent preferential association with vascular tissues or with the bundle sheath. These results show that M6PR and, thus, mannitol synthesis are closely associated with the distribution of photosynthetic carbon metabolism in celery leaves. The principal role of M6PR is, therefore, in the assimilation of carbon being exported from the chloroplast, and it seems unlikely that this enzyme plays even an indirect role in phloem loading of mannitol.

  8. 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.

  9. [Results of active surveillance in low and intermediate risk prostate cancer].

    PubMed

    Llorente, Carlos; Diaz Goizueta, Francisco Javier; Hernandez, Virginia; de la Morena, Jose Manuel; de la Peña, Enrique

    2014-06-01

    In this article we review the most significant published papers on active surveillance in prostate cancer and present the results of our case series. We used as main response variables the percentage of patients remaining in surveillance and the oncological results presented as global, cancer specific and metastasis free survivals. Globally, in published series 71.2% of patients included in active surveillance programs, 10-year overall survival is 68% in the series with longer follow up, and cancer-specific survival varies from 97% to 100%. In our series of 144 patients with median follow up of 3.2 years, 76.3% of the patients continue on surveillance. 24 patients (15.9%) stopped surveillance due to histological progression. 5 patients (21.3%) out of the 23 undergoing surgery presented unfavorable pathological criteria on prostatectomy specimen. No patient has died or developed metastases.

  10. 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. PMID:26820485

  11. 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.

  12. Results From NICLAKES Survey of Active Faulting Beneath Lake Nicaragua, Central American Volcanic Arc

    NASA Astrophysics Data System (ADS)

    Funk, J.; Mann, P.; McIntosh, K.; Wulf, S.; Dull, R.; Perez, P.; Strauch, W.

    2006-12-01

    In May of 2006 we used a chartered ferry boat to collect 520 km of seismic data, 886 km of 3.5 kHz subbottom profiler data, and 35 cores from Lake Nicaragua. The lake covers an area of 7700 km2 within the active Central American volcanic arc, forms the largest lake in Central America, ranks as the twentieth largest freshwater lake in the world, and has never been previously surveyed or cored in a systematic manner. Two large stratovolcanoes occupy the central part of the lake: Concepcion is presently active, Maderas was last active less than 2000 years ago. Four zones of active faulting and doming of the lake floor were mapped with seismic and 3.5 kHz subbottom profiling. Two of the zones consist of 3-5-km-wide, 20-30-km-long asymmetric rift structures that trend towards the inactive cone of Maderas Volcano in a radial manner. The northeastern rift forms a 20-27-m deep depression on the lake bottom that is controlled by a north-dipping normal fault. The southwestern rift forms a 25-35-m deep depression controlled by a northeast-dipping normal fault. Both depressions contain mound-like features inferred to be hydrothermal deposits. Two zones of active faulting are associated with the active Concepcion stratovolcano. A 600-m-wide and 6-km-long fault bounded horst block extends westward beneath the lake from a promontory on the west side of the volcano. Like the two radial rift features of Maderas, the horst points roughly towards the active caldera of Concepcion. A second north-south zone of active faulting, which also forms a high, extends off the north coast of Concepcion and corresponds to a localized zone of folding and faulting mapped by previous workers and inferred by them to have formed by gravitational spreading of the flank of the volcano. The close spatial relation of these faults to the two volcanic cones in the lake suggests that the mechanism for faulting is a result of either crustal movements related to magma intrusion or gravitational sliding and is

  13. 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

  14. OMP gene deletion results in an alteration in odorant-induced mucosal activity patterns.

    PubMed

    Youngentob, S L; Kent, P F; Margolis, F L

    2003-12-01

    Previous behavioral work, using a complex five-odorant identification task, demonstrated that olfactory marker protein (OMP) is critically involved in odor processing to the extent that its loss results in an alteration in odorant quality perception. Exactly how the lack of OMP exerts its influence on the perception of odorant quality is unknown. However, there is considerable neurophysiological evidence that different odorants produce different spatiotemporal patterns of neural activity at the level of the mucosa and that these patterns predict the psychophysically determined perceptual relationship among odorants. In this respect, OMP gene deletion is known to result in a constellation of physiologic defects (i.e., marked reduction in the electroolfactogram (EOG) and altered response and recovery kinetics) that would be expected to alter the odorant-induced spatiotemporal activity patterns that are characteristic of different odorants. This, in turn, would be expected to alter the spatiotemporal patterning of information that results from the mucosal projection onto the bulb, thereby changing odorant quality perception. To test the hypothesis that odorant-induced mucosal activity patterns are altered in mice lacking the gene for OMP, we optically recorded the fluorescent changes in response to odorant stimulation from both the septum and turbinates of both OMP-null and control mice using a voltage-sensitive dye (di-4-ANEPPS Molecular Probes, Eugene, OR) and a Dalsa 120 x 120, 12-bit CCD camera. To maintain continuity with the previous behavioral work, the odorants 2-propanol, citral, carvone, ethylacetoacetate, and propyl acetate were again used. Each odorant was randomly presented to each mucosal surface in a Latin-Square design. The results of this study demonstrated that, for both mouse strains, there do indeed exist different spatiotemporal activity patterns for different odorants. More importantly, however, these patterns significantly differed between OMP

  15. 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.

  16. Primary patellar tendon repair and early mobilization: results in an active-duty population.

    PubMed

    Enad, J G; Loomis, L L

    2001-01-01

    We retrospectively reviewed 13 patellar tendon repairs done over 32 months at a tertiary care, military medical center. Early mobilization was initiated within 2 weeks postoperatively. Clinical and functional results were statistically examined with relation to age, timing of surgery, length of follow-up, quadriceps atrophy, extensor lag, patella position, and time to full duty. At an average of 24 months' follow-up, six patients (46%) had thigh girth atrophy, and one patient (8%) had an extensor lag >5 degrees. Mean Lysholm score was 84 (range, 57 to 100). Maximum postoperative Tegner activity scores averaged 7.1 (range, 5 to 10). Clinical results classified five cases as excellent, three good, three fair, and two poor. Functional results classified three cases as excellent, four good, two fair, and four poor. Time to return to duty averaged 13 months. Our results suggest that adequate extensor function can be restored after primary repair and immediate motion therapy.

  17. The Fifth International Ice Nucleation Workshop Activities FIN-1 and FIN-2: Overview and Selected Results

    NASA Astrophysics Data System (ADS)

    Moehler, O.; Cziczo, D. J.; DeMott, P. J.; Hiranuma, N.; Petters, M. D.

    2015-12-01

    The role of aerosol particles for ice formation in clouds is one of the largest uncertainties in understanding the Earth's weather and climate systems, which is related to the poor knowledge of ice nucleation microphysics or of the nature and atmospheric abundance of ice nucleating particles (INPs). During the recent years, new mobile instruments were developed for measuring the concentration, size and chemical composition of INPs, which were tested during the three-part Fifth International Ice Nucleation (FIN) workshop. The FIN activities addressed not only instrument issues, but also important science topics like the nature of atmospheric INP and cloud ice residuals, the ice nucleation activity of relevant atmospheric aerosols, or the parameterization of ice formation in atmospheric weather and climate models. The first activity FIN-1 was conducted during November 2014 at the AIDA cloud chamber. It involved co-locating nine single particle mass spectrometers to evaluate how well they resolve the INP and ice residual composition and how spectra from different instruments compare for relevant atmospheric aerosols. We conducted about 90 experiments with mineral, carbonaceous and biological aerosol types, some also coated with organic and inorganic compounds. The second activity FIN-2 was conducted during March 2015 at the AIDA facility. A total of nine mobile INP instruments directly sampled from the AIDA aerosol chambers. Wet suspension and filter samples were also taken for offline INP processing. A refereed blind intercomparison was conducted during two days of the FIN-2 activity. The third activity FIN-3 will take place at the Desert Research Institute's Storm Peak Laboratory (SPL) in order to test the instruments' performance in the field. This contribution will introduce the FIN activities, summarize first results from the formal part of FIN-2, and discuss selected results, mainly from FIN-1 for the effect of coating on the ice nucleation (IN) by mineral

  18. SU-E-T-594: Preliminary Active Scanning Results of KHIMA

    SciTech Connect

    Kim, C; Yang, T; Chang, S; Kim, H; Lee, H; Kim, J; Jang, H; Han, G; Park, D; Hwang, W; Kim, G

    2014-06-01

    Purpose: To verify the design criteria on heavy ion beam irradiation, developing a proto type active scanning system was purposed. The active scanning system consists of scanning magnet, power supplies, beam monitors, energy modulation system, and irradiation control system. Methods: Each components of the active scanning system was designed for carbon beam first. For the fast ramping a laminated yoke was purposed. To measure incoming dose and profile, a plate and strip type of ion chambers were designed. Also, ridge filter and range shifter was manufactured. And, the scanning system was modified to adopt 45 MeV of proton beam because of the absence of carbon ion beam in Korea. The system was installed in a beam line at MC-50, KIRAMS. Also, the irradiation control system and planning software was provided. Results: The scanning experiment was performed by drawing KHIMA logo on GaF film. The logo was scanned by 237 scanning points through time normalized intensity modulation. Also, a grid points scanning was performed to measure the scanning resolution and intensity resolution. Conclusion: A prototype active scanning system was successfully designed and manufactured. Also, an initial experiment to print out a drawing on GaF film through the scanning system was completed. More experiments would be required to specify the system performance.

  19. 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.

  20. Massive transfusion protocol activation does not result in preferential use of older red blood cells.

    PubMed

    McDaniel, Lauren M; Triulzi, Darrell J; Cramer, James; Zuckerbraun, Brian S; Sperry, Jason L; Peitzman, Andrew B; Raval, Jay S; Neal, Matthew D

    2014-01-01

    Widespread, anecdotal belief exists that patients receiving massive transfusion, particularly those for whom a massive transfusion protocol (MTP) is activated, are more likely to receive older red blood cells (RBCs). Retrospective review of blood bank records from calendar year 2011 identified 131 patients emergently issued ≥10 RBC units (emergency release (ER)) prior to obtaining a type and screen. This cohort was subclassified based on whether there was MTP activation. For comparison, 176 identified patients transfused with ≥10 RBC units in a routine fashion over 24 hours represented the nonemergency release (nER) cohort. Though the median age of ER RBCs was 5 days older than nER RBCs (ER 20, nER 15 days, P < 0.001), both fell within the third week of storage. Regardless of MTP activation, transfused ER RBCs had the same median age (MTP 20, no-MTP 20 days, P = 0.069). In the ER cohort, transition to type-specific blood components increased the median age of transfused RBC units from 17 to 36 days (P < 0.001). These data refute the anecdotal belief that MTP activation results in transfusion of older RBCs. However, upon transition to type-specific blood components, the age of RBCs enters a range in which it is hypothesized that there may be a significant effect of storage age on clinical outcomes.

  1. Design of a Website on Nutrition and Physical Activity for Adolescents: Results From Formative Research

    PubMed Central

    Cullen, Karen Weber; Boushey, Carol; Konzelmann, Karen

    2012-01-01

    Background Teens do not meet guidelines for healthy eating and physical activity. The Internet may be an effective method for delivering programs that help them adopt healthy behaviors. Objective To collect information to design content and structure for a teen-friendly website promoting healthy eating and physical activity behaviors. Methods Qualitative research, encompassing both focus group and interview techniques, were used to design the website. Participants were 12-17 year olds in Houston, Texas, and West Lafayette, Indiana. Results A total of 133 participants took part in 26 focus groups while 15 participated in one-on-one interviews to provide guidance for the development of teen-friendly content and structure for an online behavior change program promoting healthy eating and physical activity to 12-17 year olds. The youth made suggestions to overcome common barriers to healthy eating and physical activity. Their feedback was used to develop “Teen Choice: Food & Fitness,” a 12-week online behavior change program, populated by 4 cartoon character role models. Conclusions It is critical that members of the target audience be included in formative research to develop behavior change programs that are relevant, appealing, and address their needs and interests. PMID:22538427

  2. 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

  3. 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

  4. Kras activation in p53-deficient myoblasts results in high-grade sarcoma formation with impaired myogenic differentiation

    PubMed Central

    McKinnon, Timothy; Venier, Rosemarie; Dickson, Brendan C.; Kabaroff, Leah; Alkema, Manon; Chen, Li; Shern, Jack F.; Yohe, Marielle E.; Khan, Javed; Gladdy, Rebecca A.

    2015-01-01

    While genomic studies have improved our ability to classify sarcomas, the molecular mechanisms involved in the formation and progression of many sarcoma subtypes are unknown. To better understand developmental origins and genetic drivers involved in rhabdomyosarcomagenesis, we describe a novel sarcoma model system employing primary murine p53-deficient myoblasts that were isolated and lentivirally transduced with KrasG12D. Myoblast cell lines were characterized and subjected to proliferation, anchorage-independent growth and differentiation assays to assess the effects of transgenic KrasG12D expression. KrasG12D overexpression transformed p53−/− myoblasts as demonstrated by an increased anchorage-independent growth. Induction of differentiation in parental myoblasts resulted in activation of key myogenic regulators. In contrast, Kras-transduced myoblasts had impaired terminal differentiation. p53−/− myoblasts transformed by KrasG12D overexpression resulted in rapid, reproducible tumor formation following orthotopic injection into syngeneic host hindlimbs. Pathological analysis revealed high-grade sarcomas with myogenic differentiation based on the expression of muscle-specific markers, such as Myod1 and Myog. Gene expression patterns of murine sarcomas shared biological pathways with RMS gene sets as determined by gene set enrichment analysis (GSEA) and were 61% similar to human RMS as determined by metagene analysis. Thus, our novel model system is an effective means to model high-grade sarcomas along the RMS spectrum. PMID:25992772

  5. The RNA-Binding Protein, Polypyrimidine Tract-Binding Protein 1 (PTBP1) Is a Key Regulator of CD4 T Cell Activation

    PubMed Central

    Valentín-Acevedo, Aníbal

    2016-01-01

    We have previously shown that the RNA binding protein, polypyrimidine tract-binding protein (PTBP1) plays a critical role in regulating the expression of CD40L in activated CD4 T cells. This is achieved mechanistically through message stabilization at late times of activation as well as by altered distribution of CD40L mRNA within distinct cellular compartments. PTBP1 has been implicated in many different processes, however whether PTBP1 plays a broader role in CD4 T cell activation is not known. To examine this question, experiments were designed to introduce shRNA into primary human CD4 T cells to achieve decreased, but not complete ablation of PTBP1 expression. Analyses of shPTB-expressing CD4 T cells revealed multiple processes including cell proliferation, activation-induced cell death and expression of activation markers and cytokines that were regulated in part by PTBP1 expression. Although there was an overall decrease in the steady-state level of several activation genes, only IL-2 and CD40L appeared to be regulated by PTBP1 at the level of RNA decay suggesting that PTBP1 is critical at different regulatory steps of expression that is gene-specific. Importantly, even though the IL-2 protein levels were reduced in cells with lowered PTBP1, the steady-state level of IL-2 mRNA was significantly higher in these cells suggesting a block at the translational level. Evaluation of T cell activation in shPTB-expressing T cells revealed that PTBP1 was linked primarily to the activation of the PLCγ1/ERK1/2 and the NF-κB pathways. Overall, our results reveal the importance of this critical RNA binding protein in multiple steps of T cell activation. PMID:27513449

  6. 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

  7. Changes in electrical activity in muscles resulting from chiropractic adjustment: a pilot study.

    PubMed

    Shambaugh, P

    1987-12-01

    This study examines the effects of chiropractic adjustment on the muscles of the back. Vertebrae that are hypomobile may be held in that state by the erector spinae muscle group; adjusting such vertebrae should result in less muscle tension. By measuring the change in electrical activity, such relaxation can be observed. Hypomobile vertebrae were found by motion palpation. The patient was then placed prone and surface electrodes were placed over the upper trapezius, upper erector spinae (T3-T5), and lumbar erector spinae (L1-L3) muscle groups on both sides of the body. The patient was adjusted using full spine toggle recoil thrusts, and postadjustment readings were taken. Results from this study show that significant changes in muscle electrical activity occur as a consequence of adjusting. On average, a 25% reduction in muscle activity was observed across the 20 subjects tested, while no significant reductions were observed with the control group of 14 subjects. Significant reductions in side-to-side imbalances were also observed.

  8. 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

  9. 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

  10. 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.

  11. 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

  12. Results From an Intervention to Improve Rural Home Food and Physical Activity Environments

    PubMed Central

    Kegler, Michelle C.; Alcantara, Iris; Veluswamy, J. K.; Haardörfer, Regine; Hotz, James A.; Glanz, Karen

    2013-01-01

    Background Ecological models of healthy eating and physical activity emphasize the influence of behavioral settings such as homes and worksites in shaping behavior. Research on home environments suggests that both social and physical aspects of the home may impact physical activity and healthy eating. Objective Using a community-based participatory research (CBPR) approach, the Emory Prevention Research Center (EPRC), Cancer Coalition of South Georgia, and the EPRC’s Community Advisory Board (CAB) designed and tested a coach-based intervention to make the home environment more supportive of healthy eating and physical activity for rural adults. Methods The 6-week intervention consisted of a tailored home environment profile, goal-setting, and behavioral contracting delivered through two home visits and two telephone calls. The study used a quasi-experimental design with data collected via telephone interviews at baseline, 2 and 4 months post-baseline. Ninety households (n = 90) completed all three telephone interviews. Results Multilevel models indicated that intervention households reported significant improvements in household food inventories, purchasing of fruit and vegetables, healthier meal preparation, meals with the TV off, and family support for healthy eating, relative to comparison households. Intervention households also reported increased exercise equipment and family support for physical activity relative to comparison households. Percent of fat intake decreased significantly, but no changes were observed for fruit and vegetable intake, physical activity, or weight among intervention relative to comparison households, although trends were generally in a positive direction. Conclusion Coaching combined with a focus on the home environment may be a promising strategy for weight gain prevention in adults. PMID:22982840

  13. 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

  14. 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

  15. Bursting activity in myelinated sensory neurons plays a key role in pain behavior induced by localized inflammation of the rat sensory anglion

    PubMed Central

    Xie, Wenrui; Strong, Judith A.; Kim, Daniel; Shahrestani, Sameam; Zhang, Jun-Ming

    2012-01-01

    Abnormal spontaneous activity of sensory neurons is observed in many different preclinical pain models, but its basis is not well understood. In this study mechanical and cold hypersensitivity were induced in rats after inflammation of the L5 dorsal root ganglion (DRG), initiated by local application of the immune stimulator zymosan in incomplete Freund’s adjuvant. Mechanical hypersensitivity was evident by day 1 and maintained for two months. The model also showed reduction of rearing behavior in a novel environment. Microelectrode recordings made in isolated whole DRG on day 3 after inflammation showed a marked increase of spontaneous activity, predominantly with a bursting pattern. The incidence was especially high (44%) in Aαβ cells. Spontaneous activity and subthreshold membrane potential oscillations were completely blocked by tetrodotoxin (500 nM) and by riluzole (10 μM), a blocker of persistent sodium currents. In vivo, local perfusion of the inflamed DRG for the first 7 days with riluzole gave long-lasting, dose-dependent reduction in mechanical pain behaviors. Riluzole perfusion did not affect mechanical sensitivity in normal animals. Unmyelinated C cells had a very low incidence of spontaneous activity and were much less affected by riluzole in vitro. Taken together these results suggest that high-frequency and/or bursting spontaneous bursting activity in Aαβ sensory neurons may play important roles in initiating pain behaviors resulting from inflammatory irritation of the DRG. PMID:22265726

  16. 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

  17. Improvement of IVF results and optimisation of quality control by using intermittent activity.

    PubMed

    Frydman, Nelly; Fanchin, Rénato; Le Dû, Anne; Bourrier, Marie Catherine; Tachdjian, Gérard; Frydman, René

    2004-11-01

    For several years the present authors' team had not been satisfied with the pregnancy rate achieved by their unit, especially in comparison with the results achieved by other teams with a similar population. A quality programme was established, and it was decided to switch from non-stop to intermittent activity. It was envisaged that this programme would provide a more realistic view of the team's activity and could also, as a secondary effect, improve its results. The team's experience of an in-series organization was presented for the management of 408 consecutive infertile couples, during 2002. The results obtained during 2002 were compared with those for two previous years. There was a significant increase (P < 0.01) in the clinical pregnancy rate per oocyte retrieval from 28.9% (2000) and 25.2% (2001) to 41% (2002) in IVF and from 23% (2000) and 26% (2001) to 38.5% (2002) in intracytoplasmic sperm injection (ICSI). A significant increase (P < 0.01) was also observed in the implantation rate, from 14.8% and 13.4% to 20% in IVF and from 12.1% and 12.9% to 23.5% in ICSI. The higher pregnancy rate was achieved without an increase in the multiple pregnancy rate. In conclusion, recent data support the hypothesis that the use of a quality management system, can, as in this case, have positive repercussions on pregnancy rates.

  18. 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.

  19. 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.

  20. Proteolysis of decellularized extracellular matrices results in loss of fibronectin and cell binding activity.

    PubMed

    Ramanathan, Anand; Karuri, Nancy

    2015-04-01

    Excessive inflammation in the chronic wound bed is believed to result in increased fibronectin (FN) proteolysis and poor tissue repair. However, FN fragments can prime the immune response and result in higher protease levels. The reciprocity between FN proteolysis and inflammation makes it challenging to determine the specific contribution of FN proteolysis in the extracellular matrix (ECM) on tissue responses. We studied the impact of proteolysis of decellularized extracellular matrices (dECMs) obtained from NIH 3T3 mouse fibroblasts on FN level and activity. The dECMs were treated with α chymotrypsin and proteolysis was stopped at different time points. The protease solution was obtained, the remaining dECM was scrapped and examined by immunoblotting and Bicinchoninic Acid assays. Fibronectin was 9.4 ± 1.8% of the total protein content in the dECM but was more susceptible to proteolysis. After 15 min of protease treatment there was a 67.6% and 11.1% decrease in FN and total protein, respectively, in the dECMs. Fibronectin fragments were present both in the proteolysis solution and in the dECM. Cell adhesion, spreading and actin extensions on dECMs decreased with increasing proteolysis time. Interestingly, the solutions obtained after proteolysis of the dECMs supported cell adhesion and spreading in a time dependent manner, thus demonstrating the presence of FN cell binding activity in the protease solution of dECMs. This study demonstrates the susceptibility of FN in the ECM to proteolysis and the resulting loss of cell adhesion due to the decrease of FN activity and places weight on bioengineering strategies to stabilize FN against proteolysis.

  1. Chronic ethanol consumption by mice results in activated splenic T cells.

    PubMed

    Song, Kejing; Coleman, Ruth A; Zhu, Xiaoyan; Alber, Carol; Ballas, Zuhair K; Waldschmidt, Thomas J; Cook, Robert T

    2002-12-01

    Previous studies have shown that T cells from human alcoholics overexpress activation or memory markers such as human leukocyte antigen-DR, CD45RO, CD57, and CD11b and may have reduced levels of CD62L. In those studies, we demonstrated that the increased CD57(+) T cell population rapidly produces interferon-gamma (IFN-gamma) and tumor necrosis factor alpha, independent of a second signal requirement, consistent with an increased effector T cell population. In contrast to the length of alcohol abuse by human alcoholics, most work with mice has involved 2-week ethanol exposures or less, which result in decreased IFN-gamma responses. In the present work, we have evaluated C57Bl/6 or BALB/c mice, which were administered 20% w/v ethanol in water for 3-13 weeks. In these mice, rapid cytoplasmic IFN-gamma expression by T cells after stimulation through the T cell receptor was significantly increased versus normals. Studies of surface-activation markers showed that T cells from chronically ethanol-fed mice had reduced CD62L expression and an increased percentage of CD44(hi) T cells. The CD44(hi) subset was largely second signal-independent for secreted IFN-gamma and interleukin (IL)-4 production at early times after stimulation. The enriched T cells of chronic ethanol mice secreted more IFN-gamma and IL-4 than controls and equivalent IL-2 at early times after stimulation (6-24 h). The overall results support the concept that in humans and mice, chronic alcohol exposure of sufficient duration results in T cell activation or sensitization in vivo and an increased percentage of the effector/memory subset.

  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. Active behavior of abdominal wall muscles: Experimental results and numerical model formulation.

    PubMed

    Grasa, J; Sierra, M; Lauzeral, N; Muñoz, M J; Miana-Mena, F J; Calvo, B

    2016-08-01

    In the present study a computational finite element technique is proposed to simulate the mechanical response of muscles in the abdominal wall. This technique considers the active behavior of the tissue taking into account both collagen and muscle fiber directions. In an attempt to obtain the computational response as close as possible to real muscles, the parameters needed to adjust the mathematical formulation were determined from in vitro experimental tests. Experiments were conducted on male New Zealand White rabbits (2047±34g) and the active properties of three different muscles: Rectus Abdominis, External Oblique and multi-layered samples formed by three muscles (External Oblique, Internal Oblique, and Transversus Abdominis) were characterized. The parameters obtained for each muscle were incorporated into a finite strain formulation to simulate active behavior of muscles incorporating the anisotropy of the tissue. The results show the potential of the model to predict the anisotropic behavior of the tissue associated to fibers and how this influences on the strain, stress and generated force during an isometric contraction. PMID:27111629

  10. Active behavior of abdominal wall muscles: Experimental results and numerical model formulation.

    PubMed

    Grasa, J; Sierra, M; Lauzeral, N; Muñoz, M J; Miana-Mena, F J; Calvo, B

    2016-08-01

    In the present study a computational finite element technique is proposed to simulate the mechanical response of muscles in the abdominal wall. This technique considers the active behavior of the tissue taking into account both collagen and muscle fiber directions. In an attempt to obtain the computational response as close as possible to real muscles, the parameters needed to adjust the mathematical formulation were determined from in vitro experimental tests. Experiments were conducted on male New Zealand White rabbits (2047±34g) and the active properties of three different muscles: Rectus Abdominis, External Oblique and multi-layered samples formed by three muscles (External Oblique, Internal Oblique, and Transversus Abdominis) were characterized. The parameters obtained for each muscle were incorporated into a finite strain formulation to simulate active behavior of muscles incorporating the anisotropy of the tissue. The results show the potential of the model to predict the anisotropic behavior of the tissue associated to fibers and how this influences on the strain, stress and generated force during an isometric contraction.

  11. Subconjunctival Sirolimus for the Treatment of Chronic Active Anterior Uveitis: Results of a Pilot Trial

    PubMed Central

    Sen, H. Nida; Larson, Theresa A.; Meleth, Annal D.; Smith, Wendy M.; Nussenblatt, Robert B.

    2012-01-01

    Purpose To evaluate the safety and possible efficacy of subconjunctival sirolimus for the treatment of chronic active anterior uveitis Design Prospective, non-randomized, open-label clinical trial. Methods This single-center pilot trial enrolled 5 patients with chronic active anterior uveitis. The study drug was administered as single subconjunctival injection of 30μL (1,320μg) sirolimus in the study eye at the baseline visit. Study visits were performed at baseline, 2 weeks, 4 weeks and monthly until 4 months, and included a complete ophthalmic exam, review of systems, adverse event assessment at each visit, physical exam and ancillary ophthalmic testing at some visits. The primary outcome measure was a 2-step reduction in the anterior chamber inflammation within 4 weeks of injection of the study drug. Results There were 3 females and 2 males; 4 patients had idiopathic anterior uveitis and one had psoriatic arthritis-associated anterior uveitis. Three of the five patients met the primary outcome criteria by showing at least a 2-step decrease in inflammation within 4 weeks, 2 patients showed a 1-step decrease in inflammation within the same time frame. No recurrence was encountered during a 4 month follow-up. There were no serious adverse events. Conclusions Subconjunctival sirolimus appears to be well tolerated in this pilot trial and shows promise as a treatment for active inflammation in patients with chronic anterior uveitis. Larger studies are needed to assess its usefulness in uveitis. PMID:22465364

  12. 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.

  13. RUNX1 Is a Key Target in t(4;11) Leukemias that Contributes to Gene Activation through an AF4-MLL Complex Interaction

    PubMed Central

    Wilkinson, Adam C.; Ballabio, Erica; Geng, Huimin; North, Phillip; Tapia, Marta; Kerry, Jon; Biswas, Debabrata; Roeder, Robert G.; Allis, C. David; Melnick, Ari; de Bruijn, Marella F.T.R.; Milne, Thomas A.

    2013-01-01

    Summary The Mixed Lineage Leukemia (MLL) protein is an important epigenetic regulator required for the maintenance of gene activation during development. MLL chromosomal translocations produce novel fusion proteins that cause aggressive leukemias in humans. Individual MLL fusion proteins have distinct leukemic phenotypes even when expressed in the same cell type, but how this distinction is delineated on a molecular level is poorly understood. Here, we highlight a unique molecular mechanism whereby the RUNX1 gene is directly activated by MLL-AF4 and the RUNX1 protein interacts with the product of the reciprocal AF4-MLL translocation. These results support a mechanism of transformation whereby two oncogenic fusion proteins cooperate by activating a target gene and then modulating the function of its downstream product. PMID:23352661

  14. 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.

  15. 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.

  16. Mek inhibition results in marked antitumor activity against metastatic melanoma patient-derived melanospheres and in melanosphere-generated xenografts.

    PubMed

    Sette, Giovanni; Fecchi, Katia; Salvati, Valentina; Lotti, Fiorenza; Pilozzi, Emanuela; Duranti, Enrico; Biffoni, Mauro; Pagliuca, Alfredo; Martinetti, Daniela; Memeo, Lorenzo; Milella, Michele; De Maria, Ruggero; Eramo, Adriana

    2013-11-16

    One of the key oncogenic pathways involved in melanoma aggressiveness, development and progression is the RAS/BRAF/MEK pathway, whose alterations are found in most patients. These molecular anomalies are promising targets for more effective anti-cancer therapies. Some Mek inhibitors showed promising antitumor activity, although schedules and doses associated with low systemic toxicity need to be defined. In addition, it is now accepted that cancers can arise from and be maintained by the cancer stem cells (CSC) or tumor-initiating cells (TIC), commonly expanded in vitro as tumorspheres from several solid tumors, including melanoma (melanospheres). Here, we investigated the potential targeting of MEK pathway by exploiting highly reliable in vitro and in vivo pre-clinical models of melanomas based on melanospheres, as melanoma initiating cells (MIC) surrogates. MEK inhibition, through PD0325901, provided a successful strategy to affect survival of mutated-BRAF melanospheres and growth of wild type-BRAF melanospheres. A marked citotoxicity was observed in differentated melanoma cells regardless BRAF mutational status. PD0325901 treatment, dramatically inhibited growth of melanosphere-generated xenografts and determined impaired tumor vascularization of both mutated- and wild type-BRAF tumors, in the absence of mice toxicity. These results suggest that MEK inhibition might represent a valid treatment option for patients with both mutated- or wild type-BRAF melanomas, affecting tumor growth through multiple targets.

  17. Results and Activities in RDA and their Potential for Efficient Data Processing

    NASA Astrophysics Data System (ADS)

    Wittenburg, Peter; Stehouwer, Herman; Pennington, Rob

    2015-04-01

    A large cross-disciplinary survey on data practices in Europe with about 120 interviews and intensive meetings revealed that working with data is extremely inefficient and costly. In addition our methods in the departments are such that only a small percentage of papers resulting from data intensive research is reproducible. A workshop organized by Research Data Alliance and MPS with leading scientists from various disciplines came to similar conclusions. This is the reason why the global and cross-disciplinary Research Data Alliance started working on aspects of data management, description/ annotation,access, re-use, interoperability etc. Already after 18 months the first working groups came up with their results that have the potential to help overcoming the current situation. Agreeing on a common basic data model would help in many data operations, re-using best practices for practical policies would improve reproducibility, making use of a common API for registering and resolving persistent identifiers would make usage of persistent identifier services much simpler and thus increase trust in data and making use of data type registries would help us to deal with unknown data types which is a usual phenomenon in data science. In addition, after 2 years of intensive discussions new groups have been formed such as Data Fabric which is analyzing data life cycle phases and the scientific data processing machinery to identify essential common components and services and place the activities of current working and interest groups into this language. Many data scientists are involved in these discussions which gives us hope in quick convergence. Based on a few projects that started to uptake these results and the broad interest in the new activities we can see the huge potential of them. In a presentation we will describe these first results and their potential impact for data intensive science and we will describe the objectives behind discussions of Data Fabric and

  18. A highly sensitive telomerase activity assay that eliminates false-negative results caused by PCR inhibitors.

    PubMed

    Yaku, Hidenobu; Murashima, Takashi; Miyoshi, Daisuke; Sugimoto, Naoki

    2013-01-01

    An assay for telomerase activity based on asymmetric polymerase chain reaction (A-PCR) on magnetic beads (MBs) and subsequent application of cycling probe technology (CPT) is described. In this assay, the telomerase reaction products are immobilized on MBs, which are then washed to remove PCR inhibitors that are commonly found in clinical samples. The guanine-rich sequences (5'-(TTAGGG)n-3') of the telomerase reaction products are then preferentially amplified by A-PCR, and the amplified products are subsequently detected via CPT, where a probe RNA with a fluorophore at the 5' end and a quencher at the 3' end is hydrolyzed by RNase H in the presence of the target DNA. The catalyst-mediated cleavage of the probe RNA enhances fluorescence from the 5' end of the probe. The assay allowed us to successfully detect HeLa cells selectively over normal human dermal fibroblast (NHDF) cells. Importantly, this selectivity produced identical results with regard to detection of HeLa cells in the absence and presence of excess NHDF cells; therefore, this assay can be used for practical clinical applications. The lower limit of detection for HeLa cells was 50 cells, which is lower than that achieved with a conventional telomeric repeat amplification protocol assay. Our assay also eliminated false-negative results caused by PCR inhibitors. Furthermore, we show that this assay is appropriate for screening among G-quadruplex ligands to find those that inhibit telomerase activity.

  19. OFF-GAS MERCURY CONTROL USING SULFUR-IMPREGNATED ACTIVATED CARBON – TEST RESULTS

    SciTech Connect

    Nick Soelberg

    2007-05-01

    Several laboratory and pilot-scale tests since the year 2000 have included demonstrations of off-gas mercury control using fixed bed, sulfur-impregnated activated carbon. These demonstrations have included operation of carbon beds with gas streams containing a wide range of mercury and other gas species concentrations representing off-gas from several U.S. Department of Energy (DOE) mixed waste treatment processes including electrical resistance heated (joule-heated) glass melters, fluidized bed calciners, and fluidized bed steam reformers. Surrogates of various DOE mixed waste streams (or surrogates of offgas from DOE mixed waste streams) including INL “sodium bearing waste” (SBW), liquid “low activity waste” (LAW) from the Pacific Northwest National Laboratory, and liquid waste from Savannah River National Laboratory (“Tank 48H waste”) have been tested. Test results demonstrate mercury control efficiencies up to 99.999%, high enough to comply with the Hazardous Waste (HWC) Combustor Maximum Achievable Control Technology (MACT) standards even when the uncontrolled off-gas mercury concentrations exceed 400,000 ug/dscm (at 7% O2), and confirm carbon bed design parameters for such high efficiencies. Results of several different pilot-scale and engineering-scale test programs performed over several years are presented and compared.

  20. A highly sensitive telomerase activity assay that eliminates false-negative results caused by PCR inhibitors.

    PubMed

    Yaku, Hidenobu; Murashima, Takashi; Miyoshi, Daisuke; Sugimoto, Naoki

    2013-01-01

    An assay for telomerase activity based on asymmetric polymerase chain reaction (A-PCR) on magnetic beads (MBs) and subsequent application of cycling probe technology (CPT) is described. In this assay, the telomerase reaction products are immobilized on MBs, which are then washed to remove PCR inhibitors that are commonly found in clinical samples. The guanine-rich sequences (5'-(TTAGGG)n-3') of the telomerase reaction products are then preferentially amplified by A-PCR, and the amplified products are subsequently detected via CPT, where a probe RNA with a fluorophore at the 5' end and a quencher at the 3' end is hydrolyzed by RNase H in the presence of the target DNA. The catalyst-mediated cleavage of the probe RNA enhances fluorescence from the 5' end of the probe. The assay allowed us to successfully detect HeLa cells selectively over normal human dermal fibroblast (NHDF) cells. Importantly, this selectivity produced identical results with regard to detection of HeLa cells in the absence and presence of excess NHDF cells; therefore, this assay can be used for practical clinical applications. The lower limit of detection for HeLa cells was 50 cells, which is lower than that achieved with a conventional telomeric repeat amplification protocol assay. Our assay also eliminated false-negative results caused by PCR inhibitors. Furthermore, we show that this assay is appropriate for screening among G-quadruplex ligands to find those that inhibit telomerase activity. PMID:24071983

  1. 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.

  2. Changes in diet and physical activity resulting from the Shape Up Somerville community intervention

    PubMed Central

    2013-01-01

    Background The purpose of this study is to describe the behavioral changes in children resulting from Shape Up Somerville (SUS), a community-based, participatory obesity prevention intervention that used a multi-level, systems-based approach. It was set in Somerville, an urban, culturally diverse community in Massachusetts, USA. Methods This was a non-randomized, controlled 2-year community-based intervention trial with children enrolled in grades 1 to 3 (ages 6-8 years). Overall, the SUS intervention was designed to create environmental and policy change to impact all aspects of a child’s day. Pre-post outcomes were compared between Somerville and two control communities that were chosen based on socio-demographic similarities. Behavioral outcomes were fruit and vegetable and sugar-sweetened beverage consumption; number of organized sports and physical activities per year; walking to and from school; screen and television time; television in bedroom; and dinner in room with television on. These measures were assessed by parent/caregiver report using a 68-item Family Survey Form. Data were analyzed using multiple linear regression, accounting for covariates and clustering by community. Results Intervention group children, compared to the control group, significantly reduced sugar-sweetened beverage consumption (-2.0 ounces per day; 95% CI -3.8 to -0.2), increased participation in organized sports and physical activities (0.20 sports or activities per year; 95% CI 0.06 to 0.33), and reduced their screen time (-0.24 hours per day; 95% CI -0.42 to -0.06). Conclusions Results of this study, particularly intake of sugar-sweetened beverages and screen time, are similar to others that used a multi-level approach to realize change in behavior. These results support the efficacy of a multi-level and systems-based approach for promoting the behavioral changes necessary for childhood obesity prevention. This study is registered at ClinicalTrials.gov as NCT00153322. PMID

  3. Active matrix organic light emitting diode (OLED)-XL life test results

    NASA Astrophysics Data System (ADS)

    Fellowes, David A.; Wood, Michael V.; Hastings, Arthur R., Jr.; Ghosh, Amalkumar P.; Prache, Olivier

    2008-04-01

    OLED displays have been known to exhibit high levels of performance with regards to contrast, response time, uniformity, and viewing angle, but a lifetime improvement has been perceived to be essential for broadening the applications of OLED's in the military and in the commercial market. As a result of this need, the US Army and eMagin Corporation established a Cooperative Research and Development Agreement (CRADA) to improve the lifetime of OLED displays. In 2006, eMagin Corporation developed long-life OLED-XL devices for use in their AMOLED microdisplays for head-worn applications, and RDECOM CERDEC NVESD ran life tests on these displays, finding over 200% lifetime improvement for the XL devices over the standard displays. Early results were published at the 2007 SPIE Defense and Security Symposium. Further life testing of XL and standard devices at ambient conditions and at high temperatures will be presented this year along with a recap of previous data. This should result in a better understanding of the applicability of AMOLEDs in military and commercial head mounted systems: where good fits are made, and where further development might be needed. This is a continuation of the paper "Life test results of OLED-XL long-life devices for use in active matrix organic light emitting diode (AMOLED) displays for head mounted applications" presented at SPIE DSS in 2007.

  4. Intravenous Tissue Plasminogen Activator Can Be Safely Given without Complete Blood Count Results Back

    PubMed Central

    Dong, Yi; Yang, Lumeng; Ren, Jinma; Nair, Deepak S.; Parker, Sarah; Jahnel, Jan L.; Swanson-Devlin, Teresa G.; Beck, Judith M.; Mathews, Maureen; McNeil, Clayton J.; Ling, Yifeng; Cheng, Xin; Gao, Yuan; Dong, Qiang; Wang, David Z.

    2015-01-01

    Introduction It is well known that the efficacy of intravenous (IV) tissue plasminogen activator (tPA) is time-dependent when used to treat patients with acute ischemic strokes. Aim Our study examines the safety issue of giving IV tPA without complete blood count (CBC) resulted. Materials and Methods This is a retrospective observational study by examining the database from Huashan Hospital in China and OSF/INI Comprehensive Stroke Center in United States. Patient data collected included demographics, occurrence of symptomatic intracranial hemorrhage, door to needle intervals, National Institute of Health Stroke Scale scores on admission, CBC results on admission and follow-up modified Rankin Scale scores. Linear regression and multivariable logistic regression analysis were used to identify factors that would have an impact on door-to-needle intervals. Results Our study included120 patients from Huashan Hospital and 123 patients from INI. Among them, 36 in Huashan Hospital and 51in INI received IV tPA prior to their CBC resulted. Normal platelet count was found in 98.8% patients after tPA was given. One patient had thrombocytopenia but no hemorrhagic event. A significantly shorter door to needle interval (DTN) was found in the group without CBC resulted. There was also a difference in treatment interval between the two hospitals. Door to needle intervals had a strong correlation to onset to treatment intervals and NIHSS scores on admission. Conclusion In patients presented with acute ischemic stroke, the risk of developing hemorrhagic event is low if IV tPA is given before CBC has resulted. The door to needle intervals can be significantly reduced. PMID:26147994

  5. Brain activity mapping in Mecp2 mutant mice reveals functional deficits in forebrain circuits, including key nodes in the default mode network, that are reversed with ketamine treatment.

    PubMed

    Kron, Miriam; Howell, C James; Adams, Ian T; Ransbottom, Michael; Christian, Diana; Ogier, Michael; Katz, David M

    2012-10-01

    Excitatory-inhibitory imbalance has been identified within specific brain microcircuits in models of Rett syndrome (RTT) and other autism spectrum disorders (ASDs). However, macrocircuit dysfunction across the RTT brain as a whole has not been defined. To approach this issue, we mapped expression of the activity-dependent, immediate-early gene product Fos in the brains of wild-type (Wt) and methyl-CpG-binding protein 2 (Mecp2)-null (Null) mice, a model of RTT, before and after the appearance of overt symptoms (3 and 6 weeks of age, respectively). At 6 weeks, Null mice exhibit significantly less Fos labeling than Wt in limbic cortices and subcortical structures, including key nodes in the default mode network. In contrast, Null mice exhibit significantly more Fos labeling than Wt in the hindbrain, most notably in cardiorespiratory regions of the nucleus tractus solitarius (nTS). Using nTS as a model, whole-cell recordings demonstrated that increased Fos expression in Nulls at 6 weeks of age is associated with synaptic hyperexcitability, including increased frequency of spontaneous and miniature EPSCs and increased amplitude of evoked EPSCs in Nulls. No such effect of genotype on Fos or synaptic function was seen at 3 weeks. In the mutant forebrain, reduced Fos expression, as well as abnormal sensorimotor function, were reversed by the NMDA receptor antagonist ketamine. In light of recent findings that the default mode network is hypoactive in autism, our data raise the possibility that hypofunction within this meta-circuit is a shared feature of RTT and other ASDs and is reversible. PMID:23035095

  6. Dust loading in Gusev crater, Mars: Results from two active dust devil seasons

    NASA Astrophysics Data System (ADS)

    Waller, D. A.; Greeley, R.; Neakrase, L. D.; Landis, G. A.; Whelley, P.; Thompson, S. D.

    2009-12-01

    Dust devils dominate the volcanic plains at the Mars Exploration Rover (MER) landing site within the Low Albedo Zone (LAZ) in Gusev Crater. Previous studies indicate that the inferred pressure drop within the dust devil core allows the vortex to lift large amounts of unconsolidated dust high into the atmosphere which contributes to the atmospheric haze. Previous laboratory results indicate that dust devils are efficient in lifting very fine-grained (<10 μm) material, even when boundary layer winds do not exceed previously predicted threshold wind speeds (~30-35 m/s at 1.5 m above the surface for Mars conditions). Since landing in Gusev crater in January 2004, MER Spirit has obtained data for two dust devil seasons (defined as the period of time when the first and last dust devils were imaged), with a third season currently being analyzed. These seasons typically correspond to southern spring and summer, when winds capable of lifting sediment are determined to be most frequent. All observations for Season One were taken as Spirit neared the summit of Husband Hill. During Season Two Spirit imaged dust devils in the plains as it traversed within the Inner Basin, a low-lying area in the Columbia Hills complex. All results were extrapolated so that they are representative of the entire LAZ. Season One lasted 270 sols (March 2005 to December 2005 corresponding to Ls 173.2 to 339.5 degrees), whereas Season Two lasted 153 sols (January 2007 to June 2007 corresponding to Ls 171.2 to 266.7 degrees) and ended suddenly on sol 1240 just after the dust devil frequency peaked for the season. This abrupt drop in dust devil activity corresponded to atmospheric opacity levels that exceeded 1.0 and the onset of a global dust storm that originated in the southern hemisphere that engulfed Gusev within weeks. Results show a large contrast in activity between the two seasons. An 81% decrease in dust devil frequency across the plains was found in Season Two. 533 dust devils were imaged

  7. 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

  8. 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…

  9. Commissioning activities and first results from the collective Thomson scattering diagnostic on ASDEX Upgrade (invited)

    SciTech Connect

    Meo, F.; Bindslev, H.; Korsholm, S. B.; Furtula, V.; Leipold, F.; Michelsen, P. K.; Nielsen, S. K.; Salewski, M.; Leuterer, F.; Woskov, P.; Stober, J.; Wagner, D.

    2008-10-15

    The collective Thomson scattering (CTS) diagnostic installed on ASDEX Upgrade uses millimeter waves generated by the newly installed 1 MW dual frequency gyrotron as probing radiation at 105 GHz. It measures backscattered radiation with a heterodyne receiver having 50 channels (between 100 and 110 GHz) to resolve the one-dimensional velocity distribution of the confined fast ions. The steerable antennas will allow different scattering geometries to fully explore the anisotropic fast ion distributions at different spatial locations. This paper covers the capabilities and operational limits of the diagnostic. It then describes the commissioning activities carried out to date. These activities include gyrotron studies, transmission line alignment, and beam pattern measurements in the vacuum vessel. Overlap experiments in near perpendicular and near parallel have confirmed the successful alignment of the system. First results in near perpendicular of scattered spectra in a neutral beam injection (NBI) and ion cyclotron resonance heating (ICRH) plasma (minority hydrogen) on ASDEX Upgrade have shown evidence of ICRH heating phase of hydrogen.

  10. Commissioning activities and first results from the collective Thomson scattering diagnostic on ASDEX Upgrade (invited).

    PubMed

    Meo, F; Bindslev, H; Korsholm, S B; Furtula, V; Leuterer, F; Leipold, F; Michelsen, P K; Nielsen, S K; Salewski, M; Stober, J; Wagner, D; Woskov, P

    2008-10-01

    The collective Thomson scattering (CTS) diagnostic installed on ASDEX Upgrade uses millimeter waves generated by the newly installed 1 MW dual frequency gyrotron as probing radiation at 105 GHz. It measures backscattered radiation with a heterodyne receiver having 50 channels (between 100 and 110 GHz) to resolve the one-dimensional velocity distribution of the confined fast ions. The steerable antennas will allow different scattering geometries to fully explore the anisotropic fast ion distributions at different spatial locations. This paper covers the capabilities and operational limits of the diagnostic. It then describes the commissioning activities carried out to date. These activities include gyrotron studies, transmission line alignment, and beam pattern measurements in the vacuum vessel. Overlap experiments in near perpendicular and near parallel have confirmed the successful alignment of the system. First results in near perpendicular of scattered spectra in a neutral beam injection (NBI) and ion cyclotron resonance heating (ICRH) plasma (minority hydrogen) on ASDEX Upgrade have shown evidence of ICRH heating phase of hydrogen.

  11. Oscillatory activity in developing prefrontal networks results from theta-gamma-modulated synaptic inputs.

    PubMed

    Bitzenhofer, Sebastian H; Sieben, Kay; Siebert, Kai D; Spehr, Marc; Hanganu-Opatz, Ileana L

    2015-04-21

    The hippocampus-driven entrainment of neonatal prefrontal circuits in theta-gamma oscillations contributes to the maturation of cognitive abilities, yet the underlying synaptic mechanisms are still unknown. Here we combine patch-clamp recordings from morphologically and neurochemically characterized layer V pyramidal neurons and interneurons in vivo, with extracellular recordings from the prelimbic cortex (PL) of awake and lightly anesthetized neonatal rats, to elucidate the synaptic framework of early network oscillations. We demonstrate that all neurons spontaneously fire bursts of action potentials. They receive barrages of fast and slow glutamatergic as well as GABAergic synaptic inputs. Oscillatory theta activity results from long-range coupling of pyramidal neurons, presumably within prelimbic-hippocampal circuits, and from local interactions between interneurons. In contrast, beta-low gamma activity requires external glutamatergic drive on prelimbic interneurons. High-frequency oscillations in layer V are independent of interactions at chemical synapses. Thus, specific theta-gamma-modulated synaptic interactions represent the substrate of network oscillations in the developing PL. PMID:25865885

  12. Results of IPS Observations in the Period Near Solar Activity Minimum

    NASA Astrophysics Data System (ADS)

    Chashei, I. V.; Shishov, V. I.; Tyul'bashev, S. A.; Subaev, I. A.; Oreshko, V. V.

    2013-07-01

    IPS observations with the Big Scanning Array of Lebedev Physical Institute (BSA LPI) radio telescope at the frequency 111 MHz have been monitored since 2006. All the sources, about several hundred daily, with a scintillating flux greater than 0.2 Jy are recorded for 24 hours in the 16 beams of the radio telescope covering a sky strip of 8∘ declination width. We present some results of IPS observations for the recent period of low solar activity considering a statistical ensemble of scintillating radio sources. The dependences of the averaged over ensemble scintillation index on heliocentric distance are considerably weaker than the dependence expected for a spherically symmetric geometry. The difference is especially pronounced in the year 2008 during the very deep solar activity minimum period. These features are explained by the influence of the heliospheric current sheet that is seen as a strong concentration of turbulent solar wind plasma aligned with the solar equatorial plane. A local maximum of the scintillation index is found in the anti-solar direction. Future prospects of IPS observations using BSA LPI are briefly discussed.

  13. Sonic hedgehog shedding results in functional activation of the solubilized protein.

    PubMed

    Ohlig, Stefanie; Farshi, Pershang; Pickhinke, Ute; van den Boom, Johannes; Höing, Susanne; Jakuschev, Stanislav; Hoffmann, Daniel; Dreier, Rita; Schöler, Hans R; Dierker, Tabea; Bordych, Christian; Grobe, Kay

    2011-06-14

    All Hedgehog (Hh) proteins are released from producing cells despite being synthesized as N- and C-terminally lipidated, membrane-tethered molecules. Thus, a cellular mechanism is needed for Hh solubilization. We previously suggested that a disintegrin and metalloprotease (ADAM)-mediated shedding of Sonic hedgehog (ShhNp) from its lipidated N and C termini results in protein solubilization. This finding, however, seemed at odds with the established role of N-terminal palmitoylation for ShhNp signaling activity. We now resolve this paradox by showing that N-palmitoylation of ShhNp N-terminal peptides is required for their proteolytic removal during solubilization. These peptides otherwise block ShhNp zinc coordination sites required for ShhNp binding to its receptor Patched (Ptc), explaining the essential yet indirect role of N-palmitoylation for ShhNp function. We suggest a functional model in which membrane-tethered multimeric ShhNp is at least partially autoinhibited in trans but is processed into fully active, soluble multimers upon palmitoylation-dependent cleavage of inhibitory N-terminal peptides. PMID:21664575

  14. 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.

  15. 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] .

  16. Tetraploidization of diploid Dioscorea results in activation of the antioxidant defense system and increased heat tolerance.

    PubMed

    Zhang, Xiao-Yi; Hu, Chun-Gen; Yao, Jia-Ling

    2010-01-15

    Polyploidy is reported to show increased tolerance to environmental stress. In this work, tetraploid plants of Dioscorea zingiberensis were obtained by colchicine treatment of shoots propagated in vitro. The highest tetraploid induction rate was achieved by treatment with 0.15% colchicine for 24h. Diploid and tetraploid plants were exposed to normal (28 degrees C) and high temperature (42 degrees C) for 5d during which physiological indices were measured. Compared with diploid plants, relative electrolyte leakage and contents of malondialdehyde, superoxide anions and hydrogen peroxide were lower in tetraploids, while activities of antioxidant enzymes, such as superoxide dismutase, peroxidase, catalase, ascorbate peroxidase and glutathione reductase, were stimulated and antioxidants (ascorbic acid and glutathione) were maintained at high concentrations. These results indicate that tetraploid plants possess a stronger antioxidant defense system and increased heat tolerance. PMID:19692145

  17. Characterization of a photon-counting intensified active pixel sensor (PC-IAPS): preliminary results

    NASA Astrophysics Data System (ADS)

    Uslenghi, Michela C.; Bonanno, Giovanni; Belluso, Massimiliano; Modica, Angelo; Bergamini, Paolo

    2001-12-01

    We report about preliminary results of the characterization of a new kind of MCP-based detector: a Photon Counting Intensified Active Pixel Sensor (APS). PC-IAPS appears as the natural evolution of the Intensified CCD, maintaining the basic characteristics, but with improved performance in terms of dynamic range, along with some other appealing properties: higher radiation hardness, more compact design, lower requirements on the external electronics, low power consumption. The prototype we realized is currently in an early stage of development. Nevertheless, it allows us to demonstrate the feasibility of the photon counter and to measure some of the basic parameters. Some of the characteristics of the APS, relevant to the use in intensified systems, are analyzed and compared with the CCD ones, demonstrating the potentiality of the new device and allowing us to set the basis of future development.

  18. 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%.

  19. 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.

  20. 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.

  1. 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.

  2. 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%. PMID:26737144

  3. 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.

  4. 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.

  5. Modulation of cortical activity as a result of voluntary postural sway direction: an EEG study

    PubMed Central

    Slobounov, Semyon; Hallett, Mark; Cao, Cheng; Newell, Karl

    2008-01-01

    There is increasing evidence demonstrating the role of the cerebral cortex in human postural control. Modulation of EEG both in voltage and frequency domains has been observed preceding and following self-paced postural movements and those induced by external perturbations. The current study set out to provide additional evidence regarding the role of cerebral cortex in human postural control by specifically examining modulation of EEG as a function of postural sway direction. Twelve neurologically normal subjects were instructed to produce self-paced voluntary postural sways in the anterior-posterior (AP) and medial-lateral (ML) directions. The center of pressure dynamics and EEG both in voltage and frequency domains were extracted by averaging and Morlet wavelet techniques, respectively. The amplitude of movement-related cortical potentials (MRCP) was significantly higher preceding ML sways. Also, time-frequency wavelet coefficients (TF) indicated differential modulation of EEG within alpha, beta and gamma bands as a function of voluntary postural sway direction. Thus, ML sway appear to be more difficult and energy demanding tasks than the AP sway as reflected in differential modulation of EEG. These results are discussed within the conceptual framework of differential patterns of brain activation as a result of postural task complexity. PMID:18639613

  6. 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.

  7. Disruption of PPARγ signaling results in mouse prostatic intraepithelial neoplasia involving active autophagy

    PubMed Central

    Jiang, Ming; Fernandez, Suzanne; Jerome, W. Gray; He, Yue; Yu, Xiuping; Cai, Hui; Boone, Braden; Yi, Yajun; Magnuson, Mark A.; Roy-Burman, Pradip; Matusik, Robert J.; Shappell, Scott B.; Hayward, Simon W.

    2009-01-01

    Peroxisome proliferator-activated receptor-gamma (PPARγ) regulates the interface between cellular lipid metabolism, redox status and organelle differentiation. Conditional prostatic epithelial knockout of PPARγ in mice resulted in focal hyperplasia which developed into mouse prostatic intraepithelial neoplasia (mPIN). The grade of PIN became more severe with time. Electron microscopy (EM) showed accumulated secondary lysosomes containing cellular organelles and debris suggestive of autophagy. Consistent with this analysis the autophagy marker LC3 was found to be upregulated in areas of PIN in PPARγ KO tissues. We selectively knocked down PPARγ2 isoform in wild-type mouse prostatic epithelial cells and examined the consequences of this in a tissue recombination model. Histopathologically grafted tissues resembled the conditional PPARγ KO mouse prostates. EM studies of PPARγ- and PPARγ2-deficient epithelial cells in vitro were suggestive of autophagy, consistent with the prostatic tissue analysis. This was confirmed by examining expression of beclin-1 and LC3. Gene expression profiling in PPARγ-/γ2-deficient cells indicated a major dysregulation of cell cycle control and metabolic signaling networks related to peroxisomal and lysosomal maturation, lipid oxidation and degradation. The putative autophagic phenotypes of PPARγ-deficient cells could be rescued by re-expression of either γ1 or γ2 isoform. We conclude that disruption of PPARγ signaling results in autophagy and oxidative stress during mPIN pathogenesis. PMID:19834493

  8. 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.

  9. 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…

  10. 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…

  11. 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

  12. 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

  13. Active Source Tomography of Stromboli Volcano (Italy): Results From the 2006 Seismic Experiment.

    NASA Astrophysics Data System (ADS)

    Zuccarello, L.; Patanè, D.; Cocina, O.; Castellano, M.; Sgroi, T.; Favali, P.; de Gori, P.

    2008-12-01

    Stromboli island, located in the Southern Tyrrhenian sea, is the emerged part (about 900 m a.s.l.) of a 3km-high strato-volcano. Its persistent Strombolian activity, documented for over 2000 years, is sometimes interrupted by lava effusions or major explosions. Despite the amount of recent published geophysical studies aimed to clarifying eruption dynamics, the spatial extend and geometrical characteristics of the plumbing system remain poorly understood. In fact, the knowledge of the inner structure and the zones of magma storage is limited to the upper few hundreds meters of the volcanic edifice and P- and S-waves velocity models are available only in restricted areas. In order to obtain a more suitable internal structural and velocity models of the volcano, from 25 November to 2 December 2006, a seismic tomography experiment through active seismics using air-gun sources was carried out and the final Vp model is here presented. The data has been inverted for the Vp structure by using the code Simulps13q, considering a 3D grid of nodes spaced 0.5 km down to 2 km depth, beneath the central part of volcano. The results show a relatively high velocity zones located both in the inner part of the volcanic structure, at about 1km b.s.l. and in the last 200-300 m a.s.l. in correspondence with the volcanic conduit. Slower zones were located around the summit craters in agreement with volcanological and petrological informations for the area. The relatively high velocity zones could suggest the presence of intrusive bodies related to the plumbing system.

  14. Active and passive cigarette smoking and breast cancer risk: results from the EPIC cohort.

    PubMed

    Dossus, Laure; Boutron-Ruault, Marie-Christine; Kaaks, Rudolf; Gram, Inger T; Vilier, Alice; Fervers, Béatrice; Manjer, Jonas; Tjonneland, Anne; Olsen, Anja; Overvad, Kim; Chang-Claude, Jenny; Boeing, Heiner; Steffen, Annika; Trichopoulou, Antonia; Lagiou, Pagona; Sarantopoulou, Maria; Palli, Domenico; Berrino, Franco; Tumino, Rosario; Vineis, Paolo; Mattiello, Amalia; Bueno-de-Mesquita, H Bas; van Duijnhoven, Franzel J B; Bakker, Marieke F; Peeters, Petra Hm; Weiderpass, Elisabete; Bjerkaas, Eivind; Braaten, Tonje; Menéndez, Virginia; Agudo, Antonio; Sanchez, Maria-Jose; Amiano, Pilar; Tormo, Maria-Jose; Barricarte, Aurelio; Butt, Salma; Khaw, Kay-Tee; Wareham, Nicholas; Key, Tim J; Travis, Ruth C; Rinaldi, Sabina; McCormack, Valerie; Romieu, Isabelle; Cox, David G; Norat, Teresa; Riboli, Elio; Clavel-Chapelon, Françoise

    2014-04-15

    Recent cohort studies suggest that increased breast cancer risks were associated with longer smoking duration, higher pack-years and a dose-response relationship with increasing pack-years of smoking between menarche and first full-term pregnancy (FFTP). Studies with comprehensive quantitative life-time measures of passive smoking suggest an association between passive smoking dose and breast cancer risk. We conducted a study within the European Prospective Investigation into Cancer and Nutrition to examine the association between passive and active smoking and risk of invasive breast cancer and possible effect modification by known breast cancer risk factors. Among the 322,988 women eligible for the study, 9,822 developed breast cancer (183,608 women with passive smoking information including 6,264 cases). When compared to women who never smoked and were not being exposed to passive smoking at home or work at the time of study registration, current, former and currently exposed passive smokers were at increased risk of breast cancer (hazard ratios (HR) [95% confidence interval (CI)] 1.16 [1.05-1.28], 1.14 [1.04-1.25] and 1.10 [1.01-1.20], respectively). Analyses exploring associations in different periods of life showed the most important increase in risk with pack-years from menarche to FFTP (1.73 [1.29-2.32] for every increase of 20 pack-years) while pack-years smoked after menopause were associated with a significant decrease in breast cancer risk (HR = 0.53, 95% CI: 0.34-0.82 for every increase of 20 pack-years). Our results provide an important replication, in the largest cohort to date, that smoking (passively or actively) increases breast cancer risk and that smoking between menarche and FFTP is particularly deleterious.

  15. The First Results of Monitoring Galactic Magnetar Activities with MAXI/GSC

    NASA Astrophysics Data System (ADS)

    Nakagawa, Yujin; Mihara, Tatehiro; Sugizaki, Mutsumi; Kohama, Mitsuhiro; Yamamoto, Takayuki; Suzuki, Motoko; Matsuoka, Masaru; Kawai, Nobuyuki; Morii, Mikio; Sugimori, Kohsuke; Yoshida, Atsumasa; Yamaoka, Kazu-Taka; Nakahira, Satoshi; Negoro, Hitoshi; Nakajima, Motoki; Isobe, Naoki; Maxi Team

    Magnetars are strongly magnetized neutron stars with surface magnetic fields up to 1015 G. In the galactic plane, 5 soft gamma repeaters (SGRs) and 8 anomalous X-ray pulsars (AXPs) are known as X-ray counterpart of the magnetars based on observational and theoretical studies. They exhibit thermal soft X-ray emission below ˜10 keV with a few mCrab fluxes. Interest-ingly, a hard power law component was found above ˜10 keV with a very hard index of -1 using INTEGRAL and Suzaku data. Some of the SGRs and AXPs presented a flux increasing by a factor of a few. During the high flux phases, some SGRs and AXPs exhibited high burst activities (e.g., Enoto et al. 2009) and/or enhanced quiescent emission with unusual spectral properties (e.g., Kaneko et al. 2010). In order to investigate radiation mechanisms, observa-tions of the high flux phases are important as well as those of the low flux phases. Therefore continuous monitoring of the SGRs and the AXPs are crucial to know their activities. Thanks to a wide field of view and a good sensitivity of the MAXI/GSC, it is suitable for the continuous monitoring of the SGRs and the AXPs. The MAXI/GSC has a better sensi-tivity than RXTE by a factor of a few in an energy range of 2-30 keV, and therefore detects ˜4 mCrab sources using accumulated data for ˜4 weeks. Among the 5 SGRs and 8 AXPs, AXP 4U 0142+614 and AXP 1E 1048.1-5937 are detected at least. In this paper, we will re-port the first results of monitoring the galactic SGRs and AXPs such as long-term light curves with the MAXI/GSC.

  16. Active and passive cigarette smoking and breast cancer risk: results from the EPIC cohort.

    PubMed

    Dossus, Laure; Boutron-Ruault, Marie-Christine; Kaaks, Rudolf; Gram, Inger T; Vilier, Alice; Fervers, Béatrice; Manjer, Jonas; Tjonneland, Anne; Olsen, Anja; Overvad, Kim; Chang-Claude, Jenny; Boeing, Heiner; Steffen, Annika; Trichopoulou, Antonia; Lagiou, Pagona; Sarantopoulou, Maria; Palli, Domenico; Berrino, Franco; Tumino, Rosario; Vineis, Paolo; Mattiello, Amalia; Bueno-de-Mesquita, H Bas; van Duijnhoven, Franzel J B; Bakker, Marieke F; Peeters, Petra Hm; Weiderpass, Elisabete; Bjerkaas, Eivind; Braaten, Tonje; Menéndez, Virginia; Agudo, Antonio; Sanchez, Maria-Jose; Amiano, Pilar; Tormo, Maria-Jose; Barricarte, Aurelio; Butt, Salma; Khaw, Kay-Tee; Wareham, Nicholas; Key, Tim J; Travis, Ruth C; Rinaldi, Sabina; McCormack, Valerie; Romieu, Isabelle; Cox, David G; Norat, Teresa; Riboli, Elio; Clavel-Chapelon, Françoise

    2014-04-15

    Recent cohort studies suggest that increased breast cancer risks were associated with longer smoking duration, higher pack-years and a dose-response relationship with increasing pack-years of smoking between menarche and first full-term pregnancy (FFTP). Studies with comprehensive quantitative life-time measures of passive smoking suggest an association between passive smoking dose and breast cancer risk. We conducted a study within the European Prospective Investigation into Cancer and Nutrition to examine the association between passive and active smoking and risk of invasive breast cancer and possible effect modification by known breast cancer risk factors. Among the 322,988 women eligible for the study, 9,822 developed breast cancer (183,608 women with passive smoking information including 6,264 cases). When compared to women who never smoked and were not being exposed to passive smoking at home or work at the time of study registration, current, former and currently exposed passive smokers were at increased risk of breast cancer (hazard ratios (HR) [95% confidence interval (CI)] 1.16 [1.05-1.28], 1.14 [1.04-1.25] and 1.10 [1.01-1.20], respectively). Analyses exploring associations in different periods of life showed the most important increase in risk with pack-years from menarche to FFTP (1.73 [1.29-2.32] for every increase of 20 pack-years) while pack-years smoked after menopause were associated with a significant decrease in breast cancer risk (HR = 0.53, 95% CI: 0.34-0.82 for every increase of 20 pack-years). Our results provide an important replication, in the largest cohort to date, that smoking (passively or actively) increases breast cancer risk and that smoking between menarche and FFTP is particularly deleterious. PMID:24590452

  17. 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

  18. Enhanced Cationic Charge is a Key Factor in Promoting Staphylocidal Activity of α-Melanocyte Stimulating Hormone via Selective Lipid Affinity.

    PubMed

    Singh, Jyotsna; Joshi, Seema; Mumtaz, Sana; Maurya, Nancy; Ghosh, Ilora; Khanna, Shivangi; Natarajan, Vivek T; Mukhopadhyay, Kasturi

    2016-01-01

    The steady rise in antimicrobial resistance poses a severe threat to global public health by hindering treatment of an escalating spectrum of infections. We have previously established the potent activity of α-MSH, a 13 residue antimicrobial peptide, against the opportunistic pathogen Staphylococcus aureus. Here, we sought to determine whether an increase in cationic charge in α-MSH could contribute towards improving its staphylocidal potential by increasing its interaction with anionic bacterial membranes. For this we designed novel α-MSH analogues by replacing polar uncharged residues with lysine and alanine. Similar to α-MSH, the designed peptides preserved turn/random coil conformation in artificial bacterial mimic 1,2-dimyristoyl-sn-glycero-3-phosphocholine:1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (7:3, w/w) vesicles and showed preferential insertion in the hydrophobic core of anionic membranes. Increased cationic charge resulted in considerable augmentation of antibacterial potency against MSSA and MRSA. With ~18-fold better binding than α-MSH to bacterial mimic vesicles, the most charged peptide KKK-MSH showed enhanced membrane permeabilization and depolarization activity against intact S. aureus. Scanning electron microscopy confirmed a membrane disruptive mode of action for KKK-MSH. Overall, increasing the cationic charge improved the staphylocidal activity of α-MSH without compromising its cell selectivity. The present study would help in designing more effective α-MSH-based peptides to combat clinically relevant staphylococcal infections. PMID:27526963

  19. Enhanced Cationic Charge is a Key Factor in Promoting Staphylocidal Activity of α-Melanocyte Stimulating Hormone via Selective Lipid Affinity.

    PubMed

    Singh, Jyotsna; Joshi, Seema; Mumtaz, Sana; Maurya, Nancy; Ghosh, Ilora; Khanna, Shivangi; Natarajan, Vivek T; Mukhopadhyay, Kasturi

    2016-08-16

    The steady rise in antimicrobial resistance poses a severe threat to global public health by hindering treatment of an escalating spectrum of infections. We have previously established the potent activity of α-MSH, a 13 residue antimicrobial peptide, against the opportunistic pathogen Staphylococcus aureus. Here, we sought to determine whether an increase in cationic charge in α-MSH could contribute towards improving its staphylocidal potential by increasing its interaction with anionic bacterial membranes. For this we designed novel α-MSH analogues by replacing polar uncharged residues with lysine and alanine. Similar to α-MSH, the designed peptides preserved turn/random coil conformation in artificial bacterial mimic 1,2-dimyristoyl-sn-glycero-3-phosphocholine:1,2-dimyristoyl-sn-glycero-3-phospho-rac-(1-glycerol) (7:3, w/w) vesicles and showed preferential insertion in the hydrophobic core of anionic membranes. Increased cationic charge resulted in considerable augmentation of antibacterial potency against MSSA and MRSA. With ~18-fold better binding than α-MSH to bacterial mimic vesicles, the most charged peptide KKK-MSH showed en