Science.gov

Sample records for activity restriction scale

  1. Activities of microorganisms and enzymes in water-restricted environments: biological activities in aqueous compartments at micron scale

    NASA Astrophysics Data System (ADS)

    Hoppert, Michael; Mlejnek, Klaus; Seiffert, Beatrix; Mayer, Frank

    1997-07-01

    In water-in-oil microemulsions, microdroplets of water, surrounded by a layer of surfactant molecules (reversed micelles), are dispersed in an organic solvent. Various microorganisms (unicellular algae and cyanobacteria) and isolated enzymes were dispersed in microemulsions without loss of biological activity. Each biological system needed a defined quantity of water in the microemulsion for maximum activity. Under optimum conditions, microbial enzymes for various sources (hydrogenases, dehydrogenases) exhibited, besides ten-fold increase in specific activity, a temperature optimum up to 16 degree(s)C higher as compared to aqueous solutions. These experimental findings, together with theoretical considerations, imply that water structure inside reversed micelles is very different from free water, but similar to water in narrow compartments with polar or ionic surfaces. These compartments may represent a model system for environments, where (liquid) water is not available in bulk amounts, but embedded in an anhydrous matrix.

  2. Activity Scale.

    ERIC Educational Resources Information Center

    Kerpelman, Larry C.; Weiner, Michael J.

    This twenty-four item scale assesses students' actual and desired political-social activism in terms of physical participation, communication activities, and information-gathering activities. About ten minutes are required to complete the instrument. The scale is divided into two subscales. The first twelve items (ACT-A) question respondents on…

  3. 45 CFR 3.42 - Restricted activities.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 1 2012-10-01 2012-10-01 false Restricted activities. 3.42 Section 3.42 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CONDUCT OF PERSONS AND TRAFFIC ON... contrary to security regulations or Department of Health and Human Services policies, or where...

  4. 45 CFR 3.42 - Restricted activities.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 45 Public Welfare 1 2011-10-01 2011-10-01 false Restricted activities. 3.42 Section 3.42 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CONDUCT OF PERSONS AND TRAFFIC ON... contrary to security regulations or Department of Health and Human Services policies, or where...

  5. 45 CFR 3.42 - Restricted activities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 45 Public Welfare 1 2010-10-01 2010-10-01 false Restricted activities. 3.42 Section 3.42 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CONDUCT OF PERSONS AND TRAFFIC ON... contrary to security regulations or Department of Health and Human Services policies, or where...

  6. 45 CFR 3.42 - Restricted activities.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 1 2014-10-01 2014-10-01 false Restricted activities. 3.42 Section 3.42 Public Welfare Department of Health and Human Services GENERAL ADMINISTRATION CONDUCT OF PERSONS AND TRAFFIC ON... contrary to security regulations or Department of Health and Human Services policies, or where...

  7. 45 CFR 3.42 - Restricted activities.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 1 2013-10-01 2013-10-01 false Restricted activities. 3.42 Section 3.42 Public Welfare DEPARTMENT OF HEALTH AND HUMAN SERVICES GENERAL ADMINISTRATION CONDUCT OF PERSONS AND TRAFFIC ON... contrary to security regulations or Department of Health and Human Services policies, or where...

  8. 5 CFR 734.104 - Restriction of political activity.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... service members; (d) Schedule C employees, 5 CFR 213.3301, 213.3302; and (e) Any other employees who serve... 5 Administrative Personnel 2 2010-01-01 2010-01-01 false Restriction of political activity. 734... REGULATIONS (CONTINUED) POLITICAL ACTIVITIES OF FEDERAL EMPLOYEES General Provisions § 734.104 Restriction...

  9. 5 CFR 734.104 - Restriction of political activity.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... service members; (d) Schedule C employees, 5 CFR 213.3301, 213.3302; and (e) Any other employees who serve... 5 Administrative Personnel 2 2014-01-01 2014-01-01 false Restriction of political activity. 734... REGULATIONS (CONTINUED) POLITICAL ACTIVITIES OF FEDERAL EMPLOYEES General Provisions § 734.104 Restriction...

  10. 5 CFR 734.104 - Restriction of political activity.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... service members; (d) Schedule C employees, 5 CFR 213.3301, 213.3302; and (e) Any other employees who serve... 5 Administrative Personnel 2 2012-01-01 2012-01-01 false Restriction of political activity. 734... REGULATIONS (CONTINUED) POLITICAL ACTIVITIES OF FEDERAL EMPLOYEES General Provisions § 734.104 Restriction...

  11. 5 CFR 734.104 - Restriction of political activity.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... service members; (d) Schedule C employees, 5 CFR 213.3301, 213.3302; and (e) Any other employees who serve... 5 Administrative Personnel 2 2011-01-01 2011-01-01 false Restriction of political activity. 734... REGULATIONS (CONTINUED) POLITICAL ACTIVITIES OF FEDERAL EMPLOYEES General Provisions § 734.104 Restriction...

  12. 5 CFR 734.104 - Restriction of political activity.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... service members; (d) Schedule C employees, 5 CFR 213.3301, 213.3302; and (e) Any other employees who serve... 5 Administrative Personnel 2 2013-01-01 2013-01-01 false Restriction of political activity. 734... REGULATIONS (CONTINUED) POLITICAL ACTIVITIES OF FEDERAL EMPLOYEES General Provisions § 734.104 Restriction...

  13. Using shotgun sequence data to find active restriction enzyme genes.

    PubMed

    Zheng, Yu; Posfai, Janos; Morgan, Richard D; Vincze, Tamas; Roberts, Richard J

    2009-01-01

    Whole genome shotgun sequence analysis has become the standard method for beginning to determine a genome sequence. The preparation of the shotgun sequence clones is, in fact, a biological experiment. It determines which segments of the genome can be cloned into Escherichia coli and which cannot. By analyzing the complete set of sequences from such an experiment, it is possible to identify genes lethal to E. coli. Among this set are genes encoding restriction enzymes which, when active in E. coli, lead to cell death by cleaving the E. coli genome at the restriction enzyme recognition sites. By analyzing shotgun sequence data sets we show that this is a reliable method to detect active restriction enzyme genes in newly sequenced genomes, thereby facilitating functional annotation. Active restriction enzyme genes have been identified, and their activity demonstrated biochemically, in the sequenced genomes of Methanocaldococcus jannaschii, Bacillus cereus ATCC 10987 and Methylococcus capsulatus. PMID:18988632

  14. Activity restriction in mild COPD: a challenging clinical problem.

    PubMed

    O'Donnell, Denis E; Gebke, Kevin B

    2014-01-01

    Dyspnea, exercise intolerance, and activity restriction are already apparent in mild chronic obstructive pulmonary disease (COPD). However, patients may not seek medical help until their symptoms become troublesome and persistent and significant respiratory impairment is already present; as a consequence, further sustained physical inactivity may contribute to disease progression. Ventilatory and gas exchange impairment, cardiac dysfunction, and skeletal muscle dysfunction are present to a variable degree in patients with mild COPD, and collectively may contribute to exercise intolerance. As such, there is increasing interest in evaluating exercise tolerance and physical activity in symptomatic patients with COPD who have mild airway obstruction, as defined by spirometry. Simple questionnaires, eg, the modified British Medical Research Council dyspnea scale and the COPD Assessment Test, or exercise tests, eg, the 6-minute or incremental and endurance exercise tests can be used to assess exercise performance and functional status. Pedometers and accelerometers are used to evaluate physical activity, and endurance tests (cycle or treadmill) using constant work rate protocols are used to assess the effects of interventions such as pulmonary rehabilitation. In addition, alternative outcome measurements, such as tests of small airway dysfunction and laboratory-based exercise tests, are used to measure the extent of physiological impairment in individuals with persistent dyspnea. This review describes the mechanisms of exercise limitation in patients with mild COPD and the interventions that can potentially improve exercise tolerance. Also discussed are the benefits of pulmonary rehabilitation and the potential role of pharmacologic treatment in symptomatic patients with mild COPD. PMID:24940054

  15. Activity restriction in mild COPD: a challenging clinical problem

    PubMed Central

    O’Donnell, Denis E; Gebke, Kevin B

    2014-01-01

    Dyspnea, exercise intolerance, and activity restriction are already apparent in mild chronic obstructive pulmonary disease (COPD). However, patients may not seek medical help until their symptoms become troublesome and persistent and significant respiratory impairment is already present; as a consequence, further sustained physical inactivity may contribute to disease progression. Ventilatory and gas exchange impairment, cardiac dysfunction, and skeletal muscle dysfunction are present to a variable degree in patients with mild COPD, and collectively may contribute to exercise intolerance. As such, there is increasing interest in evaluating exercise tolerance and physical activity in symptomatic patients with COPD who have mild airway obstruction, as defined by spirometry. Simple questionnaires, eg, the modified British Medical Research Council dyspnea scale and the COPD Assessment Test, or exercise tests, eg, the 6-minute or incremental and endurance exercise tests can be used to assess exercise performance and functional status. Pedometers and accelerometers are used to evaluate physical activity, and endurance tests (cycle or treadmill) using constant work rate protocols are used to assess the effects of interventions such as pulmonary rehabilitation. In addition, alternative outcome measurements, such as tests of small airway dysfunction and laboratory-based exercise tests, are used to measure the extent of physiological impairment in individuals with persistent dyspnea. This review describes the mechanisms of exercise limitation in patients with mild COPD and the interventions that can potentially improve exercise tolerance. Also discussed are the benefits of pulmonary rehabilitation and the potential role of pharmacologic treatment in symptomatic patients with mild COPD. PMID:24940054

  16. Activity Restrictions after Gynecologic Surgery: Is There Evidence?

    PubMed Central

    Nygaard, Ingrid E.; Hamad, Nadia M.; Shaw, Janet M.

    2013-01-01

    Introduction Many surgeons recommend rest and restricting activities to their patients after surgery. The aim of this review is to summarize the literature regarding types of activities gynecologic surgeons restrict and intra-abdominal pressure during specific activities and to provide an overview of negative effects of sedentary behavior (rest). Methods We searched Pubmed and Scopus for years 1970 until present and excluded studies that described recovery of activities of daily living after surgery as well as those that assessed intra-abdominal pressure for other reasons such as abdominal compartment syndrome and hypertension. For our review of intra-abdominal pressure, we excluded studies that did not include a generally healthy population, or did not report maximal intra-abdominal pressures. Results We identified no randomized trial or prospective cohort study that studied the association between post-operative activity and surgical success after pelvic floor repair. The ranges of intra-abdominal pressures during specific activities are large and such pressures during activities commonly restricted and not restricted after surgery overlap considerably. There is little concordance in mean peak intra-abdominal pressures across studies. Intra-abdominal pressure depends on many factors, but not least the manner in which it is measured and reported. Conclusions Given trends towards shorter hospital stays and off work intervals, which both predispose women to higher levels of physical activity, we urge research efforts towards understanding the role of physical activity on recurrence of pelvic organ prolapse and urinary incontinence after surgery. PMID:23340879

  17. Measurement of Daily Activity in Restrictive Type Anorexia Nervosa

    PubMed Central

    Harris, Ann M.; McAlpine, Donald E.; Shirbhate, Rashmi; Manohar, Chinmay U.; Levine, James A.

    2009-01-01

    Objective The assessment of daily activity in patients with restrictive type anorexia nervosa is limited by an absence of accurate and precise technology. We wanted to test a daily activity detecting device named, the Physical Activity Monitoring System (PAMS). Method Women participants with restrictive type anorexia nervosa (n = 8, 36 ± 11 years, 17 ± 2 kg/m2) and healthy women participants (n = 8, 30 ± 11 years, 27 ± 7 kg/m2) were asked to lie, sit and stand motionless, and walk at 0.5, 1.0, 1.5, 2.0, 2.5 and 3.0 mph whilst wearing PAMS. Results For all restrictive type anorexia nervosa and healthy participants, body posture was correctly detected for all measurements (300/300). There was excellent correlation of an individual’s body acceleration with walking velocity and walking energy expenditure (r2> 0.99). Conclusions The PAMS technology could serve as a tool for lending insight into the pathophysiology of restrictive type anorexia nervosa; and potentially measuring compliance with activity recommendations for medical professionals treating individuals with restrictive type anorexia nervosa. PMID:18004719

  18. Prolonged Activity Restriction After Concussion: Are We Worsening Outcomes?

    PubMed

    DiFazio, Marc; Silverberg, Noah D; Kirkwood, Michael W; Bernier, Raquel; Iverson, Grant L

    2016-05-01

    The current treatment of concussion or mild traumatic brain injury (mTBI) is primarily based on expert consensus. Most clinical practice guidelines advise cognitive and physical rest after injury including withdrawal from normal life activities such as school attendance, sports participation, and technology use until symptoms resolve. Some individuals who sustain an mTBI experience persistent physical, cognitive, and mental health problems. Activity restriction itself may contribute to protracted recovery and other complications. Williamson's Activity Restriction Model of Depression, formulated more than 20 years ago, is central to this hypothesis. We review research evidence for potential harms of prolonged activity restriction and report an mTBI case as an example of how an "activity restriction cascade" can unfold. According to this model, psychological consequences of removal from validating life activities, combined with physical deconditioning, contribute to the development and persistence of postconcussive symptoms after mTBI in some youth. A modification to mTBI guidelines that emphasizes prompt reengagement in life activities as tolerated is encouraged. PMID:26130391

  19. 24 CFR 570.309 - Restriction on location of activities.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 24 Housing and Urban Development 3 2011-04-01 2010-04-01 true Restriction on location of activities. 570.309 Section 570.309 Housing and Urban Development Regulations Relating to Housing and Urban... HOUSING AND URBAN DEVELOPMENT COMMUNITY FACILITIES COMMUNITY DEVELOPMENT BLOCK GRANTS Entitlement...

  20. Are Dietary Restraint Scales Valid Measures of Acute Dietary Restriction? Unobtrusive Observational Data Suggest Not

    ERIC Educational Resources Information Center

    Stice, Eric; Fisher, Melissa; Lowe, Michael R.

    2004-01-01

    The finding that dietary restraint scales predict onset of bulimic pathology has been interpreted as suggesting that dieting causes this eating disturbance, despite the dearth of evidence that these scales are valid measures of dietary restriction. The authors conducted 4 studies that tested whether dietary restraint scales were inversely…

  1. Controlling the enzymatic activity of a restriction enzyme by light

    PubMed Central

    Schierling, Benno; Noël, Ann-Josée; Wende, Wolfgang; Hien, Le Thi; Volkov, Eugeny; Kubareva, Elena; Oretskaya, Tatiana; Kokkinidis, Michael; Römpp, Andreas; Spengler, Bernhard; Pingoud, Alfred

    2010-01-01

    For many applications it would be desirable to be able to control the activity of proteins by using an external signal. In the present study, we have explored the possibility of modulating the activity of a restriction enzyme with light. By cross-linking two suitably located cysteine residues with a bifunctional azobenzene derivative, which can adopt a cis- or trans-configuration when illuminated by UV or blue light, respectively, enzymatic activity can be controlled in a reversible manner. To determine which residues when cross-linked show the largest “photoswitch effect,” i.e., difference in activity when illuminated with UV vs. blue light, > 30 variants of a single-chain version of the restriction endonuclease PvuII were produced, modified with azobenzene, and tested for DNA cleavage activity. In general, introducing single cross-links in the enzyme leads to only small effects, whereas with multiple cross-links and additional mutations larger effects are observed. Some of the modified variants, which carry the cross-links close to the catalytic center, can be modulated in their DNA cleavage activity by a factor of up to 16 by illumination with UV (azobenzene in cis) and blue light (azobenzene in trans), respectively. The change in activity is achieved in seconds, is fully reversible, and, in the case analyzed, is due to a change in V max rather than K m. PMID:20080559

  2. Physically Active Rats Lose More Weight during Calorie Restriction

    PubMed Central

    Smyers, Mark E.; Bachir, Kailey Z.; Britton, Steven L.; Koch, Lauren G.; Novak, Colleen M.

    2014-01-01

    Daily physical activity shows substantial inter-individual variation, and low physical activity is associated with obesity and weight gain. Elevated physical activity is also associated with high intrinsic aerobic capacity, which confers considerable metabolic health benefits. Rats artificially selected for high intrinsic aerobic capacity (high-capacity runners, HCR) are more physically active than their low-capacity counterparts (low-capacity runners, LCR). To test the hypothesis that physical activity counters metabolic thriftiness, we measured physical activity and weight loss during three weeks of 50% calorie restriction (CR) in the HCR and LCR rat lines. At baseline, HCR ate more and were more active than LCR; this was seen in male rats, where LCR are considerably heavier than HCR, as well as in a set of female rats where body weight did not differ between the lines, demonstrating that this effect is consistent across sex and not secondary to body weight. We show for the first time that HCR lose more weight than LCR relative to baseline. Physical activity levels declined throughout CR, and this was more pronounced in HCR than in LCR, yet some aspects of activity remained elevated in HCR relative to LCR even during CR. This is consistent with the idea that low physical activity contributes to metabolic thriftiness during food restriction, allowing LCR to defend body mass, particularly lean mass. This has implications for physical activity during diet-induced weight loss, the genetic underpinnings of individual differences in weight loss during a diet, and the potential evolutionary opposition between metabolic thriftiness and aerobic capacity. PMID:25449411

  3. Physically active rats lose more weight during calorie restriction.

    PubMed

    Smyers, Mark E; Bachir, Kailey Z; Britton, Steven L; Koch, Lauren G; Novak, Colleen M

    2015-02-01

    Daily physical activity shows substantial inter-individual variation, and low physical activity is associated with obesity and weight gain. Elevated physical activity is also associated with high intrinsic aerobic capacity, which confers considerable metabolic health benefits. Rats artificially selected for high intrinsic aerobic capacity (high-capacity runners, HCR) are more physically active than their low-capacity counterparts (low-capacity runners, LCR). To test the hypothesis that physical activity counters metabolic thriftiness, we measured physical activity and weight loss during three weeks of 50% calorie restriction (CR) in the HCR and LCR rat lines. At baseline, HCR ate more and were more active than LCR; this was seen in male rats, where LCR are considerably heavier than HCR, as well as in a set of female rats where body weight did not differ between the lines, demonstrating that this effect is consistent across sex and not secondary to body weight. We show for the first time that HCR lose more weight than LCR relative to baseline. Physical activity levels declined throughout CR, and this was more pronounced in HCR than in LCR, yet some aspects of activity remained elevated in HCR relative to LCR even during CR. This is consistent with the idea that low physical activity contributes to metabolic thriftiness during food restriction, allowing LCR to defend body mass, particularly lean mass. This has implications for physical activity during diet-induced weight loss, the genetic underpinnings of individual differences in weight loss during a diet, and the potential evolutionary opposition between metabolic thriftiness and aerobic capacity. PMID:25449411

  4. Interactive Effects of Dorsomedial Hypothalamic Nucleus and Time-Restricted Feeding on Fractal Motor Activity Regulation.

    PubMed

    Lo, Men-Tzung; Chiang, Wei-Yin; Hsieh, Wan-Hsin; Escobar, Carolina; Buijs, Ruud M; Hu, Kun

    2016-01-01

    One evolutionary adaptation in motor activity control of animals is the anticipation of food that drives foraging under natural conditions and is mimicked in laboratory with daily scheduled food availability. Food anticipation is characterized by increased activity a few hours before the feeding period. Here we report that 2-h food availability during the normal inactive phase of rats not only increases activity levels before the feeding period but also alters the temporal organization of motor activity fluctuations over a wide range of time scales from minutes up to 24 h. We demonstrate this multiscale alteration by assessing fractal patterns in motor activity fluctuations-similar fluctuation structure at different time scales-that are robust in intact animals with ad libitum food access but are disrupted under food restriction. In addition, we show that fractal activity patterns in rats with ad libitum food access are also perturbed by lesion of the dorsomedial hypothalamic (DMH)-a neural node that is involved in food anticipatory behavior. Instead of further disrupting fractal regulation, food restriction restores the disrupted fractal patterns in these animals after the DMH lesion despite the persistence of the 24-h rhythms. This compensatory effect of food restriction is more clearly pronounced in the same animals after the additional lesion of the suprachiasmatic nucleus (SCN)-the central master clock in the circadian system that generates and orchestrates circadian rhythms in behavior and physiological functions in synchrony with day-night cycles. Moreover, all observed influences of food restriction persist even when data during the food anticipatory and feeding period are excluded. These results indicate that food restriction impacts dynamics of motor activity at different time scales across the entire circadian/daily cycle, which is likely caused by the competition between the food-induced time cue and the light-entrained circadian rhythm of the SCN. The

  5. Interactive Effects of Dorsomedial Hypothalamic Nucleus and Time-Restricted Feeding on Fractal Motor Activity Regulation

    PubMed Central

    Lo, Men-Tzung; Chiang, Wei-Yin; Hsieh, Wan-Hsin; Escobar, Carolina; Buijs, Ruud M.; Hu, Kun

    2016-01-01

    One evolutionary adaptation in motor activity control of animals is the anticipation of food that drives foraging under natural conditions and is mimicked in laboratory with daily scheduled food availability. Food anticipation is characterized by increased activity a few hours before the feeding period. Here we report that 2-h food availability during the normal inactive phase of rats not only increases activity levels before the feeding period but also alters the temporal organization of motor activity fluctuations over a wide range of time scales from minutes up to 24 h. We demonstrate this multiscale alteration by assessing fractal patterns in motor activity fluctuations—similar fluctuation structure at different time scales—that are robust in intact animals with ad libitum food access but are disrupted under food restriction. In addition, we show that fractal activity patterns in rats with ad libitum food access are also perturbed by lesion of the dorsomedial hypothalamic (DMH)—a neural node that is involved in food anticipatory behavior. Instead of further disrupting fractal regulation, food restriction restores the disrupted fractal patterns in these animals after the DMH lesion despite the persistence of the 24-h rhythms. This compensatory effect of food restriction is more clearly pronounced in the same animals after the additional lesion of the suprachiasmatic nucleus (SCN)—the central master clock in the circadian system that generates and orchestrates circadian rhythms in behavior and physiological functions in synchrony with day-night cycles. Moreover, all observed influences of food restriction persist even when data during the food anticipatory and feeding period are excluded. These results indicate that food restriction impacts dynamics of motor activity at different time scales across the entire circadian/daily cycle, which is likely caused by the competition between the food-induced time cue and the light-entrained circadian rhythm of the

  6. Factor Structure of the Restricted Academic Situation Scale: Implications for ADHD

    ERIC Educational Resources Information Center

    Karama, Sherif; Amor, Leila Ben; Grizenko, Natalie; Ciampi, Antonio; Mbekou, Valentin; Ter-Stepanian, Marina; Lageix, Philippe; Baron, Chantal; Schwartz, George; Joober, Ridha

    2009-01-01

    Background: To study the factor structure of the Restricted Academic Situation Scale (RASS), a psychometric tool used to assess behavior in children with ADHD, 117 boys and 21 girls meeting "Diagnostic and Statistical Manual of Mental Disorders" (4th ed.; "DSM-IV") criteria for ADHD and aged between 6 and 12 years were recruited. Assessments were…

  7. Scaling behavior of online human activity

    NASA Astrophysics Data System (ADS)

    Zhao, Zhi-Dan; Cai, Shi-Min; Huang, Junming; Fu, Yan; Zhou, Tao

    2012-11-01

    The rapid development of the Internet technology enables humans to explore the web and record the traces of online activities. From the analysis of these large-scale data sets (i.e., traces), we can get insights about the dynamic behavior of human activity. In this letter, the scaling behavior and complexity of human activity in the e-commerce, such as music, books, and movies rating, are comprehensively investigated by using the detrended fluctuation analysis technique and the multiscale entropy method. Firstly, the interevent time series of rating behaviors of these three types of media show similar scaling properties with exponents ranging from 0.53 to 0.58, which implies that the collective behaviors of rating media follow a process embodying self-similarity and long-range correlation. Meanwhile, by dividing the users into three groups based on their activities (i.e., rating per unit time), we find that the scaling exponents of the interevent time series in the three groups are different. Hence, these results suggest that a stronger long-range correlations exist in these collective behaviors. Furthermore, their information complexities vary in the three groups. To explain the differences of the collective behaviors restricted to the three groups, we study the dynamic behavior of human activity at the individual level, and find that the dynamic behaviors of a few users have extremely small scaling exponents associated with long-range anticorrelations. By comparing the interevent time distributions of four representative users, we can find that the bimodal distributions may bring forth the extraordinary scaling behaviors. These results of the analysis of the online human activity in the e-commerce may not only provide insight into its dynamic behaviors but may also be applied to acquire potential economic interest.

  8. 33 CFR 334.763 - Naval Support Activity Panama City; Gulf of Mexico; restricted area.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... City; Gulf of Mexico; restricted area. 334.763 Section 334.763 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE DANGER ZONE AND RESTRICTED AREA REGULATIONS § 334.763 Naval Support Activity Panama City; Gulf of Mexico; restricted area. (a) The area. The area...

  9. 33 CFR 334.763 - Naval Support Activity Panama City; Gulf of Mexico; restricted area.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... City; Gulf of Mexico; restricted area. 334.763 Section 334.763 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE DANGER ZONE AND RESTRICTED AREA REGULATIONS § 334.763 Naval Support Activity Panama City; Gulf of Mexico; restricted area. (a) The area. The area...

  10. 33 CFR 334.763 - Naval Support Activity Panama City; Gulf of Mexico; restricted area.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... City; Gulf of Mexico; restricted area. 334.763 Section 334.763 Navigation and Navigable Waters CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE DANGER ZONE AND RESTRICTED AREA REGULATIONS § 334.763 Naval Support Activity Panama City; Gulf of Mexico; restricted area. (a) The area. The area...

  11. Characteristics Associated with Fear of Falling and Activity Restriction in Community-Living Older Persons

    PubMed Central

    Murphy, Susan L.; Williams, Christianna S.; Gill, Thomas M.

    2011-01-01

    OBJECTIVES To identify the characteristics associated with restricting activity because of fear of falling (activity restriction) and to determine which characteristics distinguish older persons who restrict activity from those who have fear of falling but do not restrict their activities (fear of falling alone). DESIGN Population-based cross-sectional study. SETTING General community. PARTICIPANTS One thousand sixty-four community-living persons aged 72 and older. MEASUREMENTS Candidate predictors were identified from the following domains: demographic, health status, physical, psychosocial, and fall-related. The outcome measure was the report of no fear of falling, fear of falling alone, or activity restriction. RESULTS Fifty-seven percent of the cohort reported no fear of falling, 24% reported fear of falling alone, and 19% reported restricting activity. The proportion of participants with poor health status, slow timed physical performance, activities of daily living disability, and poor psychosocial function was highest in those with activity restriction, intermediate in those with fear of falling alone, and lowest in those with no fear of falling. Of participants with fear of falling, characteristics independently associated with activity restriction were history of an injurious fall, slow timed physical performance, two or more chronic conditions, and depressive symptoms. CONCLUSION Older persons who restrict activity are more physically frail and have a greater burden of chronic conditions and depressive symptoms than those who have fear of falling alone. These differences between persons with fear of falling may guide the refinement of clinical interventions and preventative programs. PMID:11943049

  12. 15 CFR 400.33 - Restrictions on manufacturing and processing activity.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false Restrictions on manufacturing and...-TRADE ZONES BOARD Manufacturing and Processing Activity-Reviews § 400.33 Restrictions on manufacturing and processing activity. (a) In general. In approving manufacturing or processing activity for a...

  13. 15 CFR 400.33 - Restrictions on manufacturing and processing activity.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 2 2010-01-01 2010-01-01 false Restrictions on manufacturing and...-TRADE ZONES BOARD Manufacturing and Processing Activity-Reviews § 400.33 Restrictions on manufacturing and processing activity. (a) In general. In approving manufacturing or processing activity for a...

  14. 15 CFR 400.33 - Restrictions on manufacturing and processing activity.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 2 2012-01-01 2012-01-01 false Restrictions on manufacturing and...-TRADE ZONES BOARD Manufacturing and Processing Activity-Reviews § 400.33 Restrictions on manufacturing and processing activity. (a) In general. In approving manufacturing or processing activity for a...

  15. Manufacturing and design of the offshore structure Froude scale model related to basin restrictions

    NASA Astrophysics Data System (ADS)

    Scurtu, I. C.

    2015-11-01

    Manufacturing steps for a modern three - column semi-submersible structure are delivered using CFD/CAE software and actual Froude scaled model testing. The three- column offshore is part of the Wind Float Project already realized as prototype for wind energy extraction in water depths more than 40 meters, and the actual model will not consider the wind turbine. The model will have heave plates for a smaller heave motion in order to compare it with the case without heave plates. The heave plates will be part of the Froude scale model.. Using a smaller model will determine a smaller heave motion and this will affect predictions of the vertical movement of the three- column offshore structure in real sea. The Froude criterion is used for the time, speed and acceleration scale. The scale model is manufactured from steel and fiberglass and all parts are subjected to software analysis in order to get the smallest stress in connections inside the model. The model mass was restricted by scale dimensions and also the vertical position of centre gravity will be considered during the manufacturing and design process of the Froude scale offshore structure. All conditions must converge in model manufacturing and design in order to get the best results to compare with real sea states and heave motion data.

  16. Efficacy of physical activity counseling plus sleep restriction therapy on the patients with chronic insomnia

    PubMed Central

    Wang, Jihui; Yin, Guangxia; Li, Guanying; Liang, Wenjing; Wei, Qinling

    2015-01-01

    Objective Lack of physical activity (PA) is common in patients with chronic insomnia. Studies to increase PA and decrease sedentary behavior in those patients are limited. Therefore, we investigated the efficacy of “PA counseling combined with sleep restriction (SR) therapy (PASR)” vs only SR in the patients with chronic insomnia. Methods Seventy-one outpatients were assigned to either PASR (n=35), consisting of four weekly PA counseling sessions based on 5A model (assess, advise, agree, assist, and arrange) + SR, or SR (n=36), consisting of four weekly SR. International Physical Activity Questionnaire (Chinese version) and pedometer-based daily steps were evaluated as the primary endpoints. Insomnia Severity Index, Epworth Sleepiness Scale, Fatigue Scale-14, and Sleep Diary were evaluated as the secondary endpoints. Results The results showed that the patients in the PASR group gained more benefits than the SR group in terms of PA level and pedometer-based daily steps (all P<0.05). Better improvements of the study group were also shown in Epworth Sleepiness Scale, Fatigue Scale-14, and Sleep efficiency (all P<0.05). Conclusion We conclude that PA counseling based on 5A model combined with SR cannot only effectively increase the PA levels but also improve the sleep quality for patients with chronic insomnia. PMID:26566369

  17. 33 CFR 334.761 - Naval Support Activity Panama City; St. Andrews Bay; restricted areas.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... City; St. Andrews Bay; restricted areas. 334.761 Section 334.761 Navigation and Navigable Waters CORPS... REGULATIONS § 334.761 Naval Support Activity Panama City; St. Andrews Bay; restricted areas. (a) The areas—(1... in this section shall be enforced by the Commanding Officer, Naval Support Activity, Panama...

  18. 15 CFR 744.6 - Restrictions on certain activities of U.S. persons.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 2 2012-01-01 2012-01-01 false Restrictions on certain activities of... REGULATIONS CONTROL POLICY: END-USER AND END-USE BASED § 744.6 Restrictions on certain activities of U.S...). (b) Additional prohibitions on U.S. persons informed by BIS. BIS may inform U.S. persons,...

  19. 15 CFR 744.6 - Restrictions on certain activities of U.S. persons.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 2 2014-01-01 2014-01-01 false Restrictions on certain activities of... REGULATIONS CONTROL POLICY: END-USER AND END-USE BASED § 744.6 Restrictions on certain activities of U.S...). (b) Additional prohibitions on U.S. persons informed by BIS. BIS may inform U.S. persons,...

  20. 15 CFR 744.6 - Restrictions on certain activities of U.S. persons.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 2 2013-01-01 2013-01-01 false Restrictions on certain activities of... REGULATIONS CONTROL POLICY: END-USER AND END-USE BASED § 744.6 Restrictions on certain activities of U.S...). (b) Additional prohibitions on U.S. persons informed by BIS. BIS may inform U.S. persons,...

  1. 15 CFR 744.6 - Restrictions on certain activities of U.S. persons.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false Restrictions on certain activities of... REGULATIONS CONTROL POLICY: END-USER AND END-USE BASED § 744.6 Restrictions on certain activities of U.S...). (b) Additional prohibitions on U.S. persons informed by BIS. BIS may inform U.S. persons,...

  2. 33 CFR 334.763 - Naval Support Activity Panama City; Gulf of Mexico; restricted area.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Naval Support Activity Panama City; Gulf of Mexico; restricted area. 334.763 Section 334.763 Navigation and Navigable Waters CORPS OF....763 Naval Support Activity Panama City; Gulf of Mexico; restricted area. (a) The area. The area...

  3. Physical activity: benefit or weakness in metabolic adaptations in a mouse model of chronic food restriction?

    PubMed

    Méquinion, Mathieu; Caron, Emilie; Zgheib, Sara; Stievenard, Aliçia; Zizzari, Philippe; Tolle, Virginie; Cortet, Bernard; Lucas, Stéphanie; Prévot, Vincent; Chauveau, Christophe; Viltart, Odile

    2015-02-01

    In restrictive-type anorexia nervosa (AN) patients, physical activity is usually associated with food restriction, but its physiological consequences remain poorly characterized. In female mice, we evaluated the impact of voluntary physical activity with/without chronic food restriction on metabolic and endocrine parameters that might contribute to AN. In this protocol, FRW mice (i.e., food restriction with running wheel) reached a crucial point of body weight loss (especially fat mass) faster than FR mice (i.e., food restriction only). However, in contrast to FR mice, their body weight stabilized, demonstrating a protective effect of a moderate, regular physical activity. Exercise delayed meal initiation and duration. FRW mice displayed food anticipatory activity compared with FR mice, which was strongly diminished with the prolongation of the protocol. The long-term nature of the protocol enabled assessment of bone parameters similar to those observed in AN patients. Both restricted groups adapted their energy metabolism differentially in the short and long term, with less fat oxidation in FRW mice and a preferential use of glucose to compensate for the chronic energy imbalance. Finally, like restrictive AN patients, FRW mice exhibited low leptin levels, high plasma concentrations of corticosterone and ghrelin, and a disruption of the estrous cycle. In conclusion, our model suggests that physical activity has beneficial effects on the adaptation to the severe condition of food restriction despite the absence of any protective effect on lean and bone mass. PMID:25465889

  4. 5 CFR 7001.102 - Restrictions on outside employment and business activities.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 3 2010-01-01 2010-01-01 false Restrictions on outside employment and business activities. 7001.102 Section 7001.102 Administrative Personnel UNITED STATES POSTAL SERVICE SUPPLEMENTAL STANDARDS OF ETHICAL CONDUCT FOR EMPLOYEES OF THE UNITED STATES POSTAL SERVICE § 7001.102 Restrictions on outside employment and...

  5. Poor Vision, Functioning, and Depressive Symptoms: A Test of the Activity Restriction Model

    ERIC Educational Resources Information Center

    Bookwala, Jamila; Lawson, Brendan

    2011-01-01

    Purpose: This study tested the applicability of the activity restriction model of depressed affect to the context of poor vision in late life. This model hypothesizes that late-life stressors contribute to poorer mental health not only directly but also indirectly by restricting routine everyday functioning. Method: We used data from a national…

  6. TRIM5 Retroviral Restriction Activity Correlates with the Ability To Induce Innate Immune Signaling

    PubMed Central

    Lascano, Josefina; Uchil, Pradeep D.; Mothes, Walther

    2015-01-01

    ABSTRACT Host restriction factor TRIM5 inhibits retroviral transduction in a species-specific manner by binding to and destabilizing the retroviral capsid lattice before reverse transcription is completed. However, the restriction mechanism may not be that simple since TRIM5 E3 ubiquitin ligase activity, the proteasome, autophagy, and TAK1-dependent AP-1 signaling have been suggested to contribute to restriction. Here, we show that, among a panel of seven primate and Carnivora TRIM5 orthologues, each of which has potential for potent retroviral restriction activity, all activated AP-1 signaling. In contrast, TRIM family paralogues most closely related to TRIM5 did not. While each primate species has a single TRIM5 gene, mice have at least seven TRIM5 homologues that cluster into two groups, Trim12a, -b, and -c and Trim30a, -b, -c, and -d. The three Trim12 proteins activated innate immune signaling, while the Trim30 proteins did not, though none of the murine Trim5 homologues restricted any of a panel of cloned retroviruses. To determine if any mouse TRIM5 homologues had potential for restriction activity, each was fused to the human immunodeficiency virus type 1 (HIV-1) CA binding protein cyclophilin A (CypA). The three Trim12-CypA fusions all activated AP-1 and restricted HIV-1 transduction, whereas the Trim30-CypA fusions did neither. AP-1 activation and HIV-1 restriction by the Trim12-CypA fusions were inhibited by disruption of TAK1. Overall then, these experiments demonstrate that there is a strong correlation between TRIM5 retroviral restriction activity and the ability to activate TAK1-dependent innate immune signaling. IMPORTANCE The importance of retroviruses for the evolution of susceptible host organisms cannot be overestimated. Eight percent of the human genome is retrovirus sequence, fixed in the germ line during past infection. Understanding how metazoa protect their genomes from mutagenic retrovirus infection is therefore of fundamental importance to

  7. Restricted gene flow and fine-scale population structuring in tool using New Caledonian crows

    NASA Astrophysics Data System (ADS)

    Rutz, C.; Ryder, T. B.; Fleischer, R. C.

    2012-04-01

    New Caledonian crows Corvus moneduloides are the most prolific avian tool users. It has been suggested that some aspects of their complex tool use behaviour are under the influence of cultural processes, involving the social transmission—and perhaps even progressive refinement—of tool designs. Using microsatellite and mt-haplotype profiling of crows from three distinct habitats (dry forest, farmland and beachside habitat), we show that New Caledonian crow populations can exhibit significant fine-scale genetic structuring. Our finding that some sites of <10 km apart were highly differentiated demonstrates considerable potential for genetic and/or cultural isolation of crow groups. Restricted movement of birds between local populations at such small spatial scales, especially across habitat boundaries, illustrates how specific tool designs could be preserved over time, and how tool technologies of different crow groups could diverge due to drift and local selection pressures. Young New Caledonian crows have an unusually long juvenile dependency period, during which they acquire complex tool-related foraging skills. We suggest that the resulting delayed natal dispersal drives population-divergence patterns in this species. Our work provides essential context for future studies that examine the genetic makeup of crow populations across larger geographic areas, including localities with suspected cultural differences in crow tool technologies.

  8. 15 CFR 970.103 - Prohibited activities and restrictions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES General § 970... United States or any other nation; and any other activity designed to harass deep seabed...

  9. 15 CFR 970.103 - Prohibited activities and restrictions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES General § 970... United States or any other nation; and any other activity designed to harass deep seabed...

  10. 15 CFR 970.103 - Prohibited activities and restrictions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR EXPLORATION LICENSES General § 970... United States or any other nation; and any other activity designed to harass deep seabed...

  11. Reduced Activity Restriction Buffers the Relations Between Chronic Stress and Sympathetic Nervous System Activation

    PubMed Central

    2014-01-01

    Objectives. Caregivers of dementia patients are at risk for developing cardiovascular disease (CVD), and this risk increases the longer they provide care. Greater perceptions that caregiving restricts social/recreational activities (i.e., activity restriction [AR]) has been associated with poorer health, and AR may exacerbate the relations between stress and health outcomes. The current study examined the interactive role of greater exposure to stress and increased AR on plasma catecholamine (CAT) levels: norepinephrine (NE) and epinephrine (EPI). Method. A total of 84 dementia caregivers completed a standard assessment battery, and a nurse collected blood, which was assayed for NE and EPI. Separate regressions for NE and EPI were used to determine whether the relations between years caregiving and CATs were greater in those with high versus low AR. Results. A significant interaction was found between years caregiving and AR in predicting resting EPI (p = .032) but not resting NE (p = .103). Post hoc analyses indicated that years caregiving was significantly associated with EPI when AR was high (p = .008) but not when AR was low (p = .799). Additionally, years caregiving was not significantly associated with NE when AR was high or low. Discussion. The subjective experience of AR can play an important role in determining risk for detrimental physical health outcomes, particularly CVD risk. PMID:23685924

  12. 15 CFR 971.103 - Prohibited activities and restrictions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... any pending application to which priority of right for issuance applies under 15 CFR part 970 or this... THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY PERMITS General... the effect of harassing, persons conducting deep seabed mining activities authorized by...

  13. 15 CFR 971.103 - Prohibited activities and restrictions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... any pending application to which priority of right for issuance applies under 15 CFR part 970 or this... THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY PERMITS General... the effect of harassing, persons conducting deep seabed mining activities authorized by...

  14. 15 CFR 971.103 - Prohibited activities and restrictions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... any pending application to which priority of right for issuance applies under 15 CFR part 970 or this... THE ENVIRONMENTAL DATA SERVICE DEEP SEABED MINING REGULATIONS FOR COMMERCIAL RECOVERY PERMITS General... the effect of harassing, persons conducting deep seabed mining activities authorized by...

  15. 33 CFR 334.761 - Naval Support Activity Panama City; St. Andrews Bay; restricted areas.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Naval Support Activity Panama... REGULATIONS § 334.761 Naval Support Activity Panama City; St. Andrews Bay; restricted areas. (a) The areas—(1... in this section shall be enforced by the Commanding Officer, Naval Support Activity, Panama...

  16. 33 CFR 334.761 - Naval Support Activity Panama City; St. Andrews Bay; restricted areas.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 3 2010-07-01 2010-07-01 false Naval Support Activity Panama... REGULATIONS § 334.761 Naval Support Activity Panama City; St. Andrews Bay; restricted areas. (a) The areas—(1... in this section shall be enforced by the Commanding Officer, Naval Support Activity, Panama...

  17. 33 CFR 334.763 - Naval Support Activity Panama City; Gulf of Mexico; restricted area.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 3 2011-07-01 2011-07-01 false Naval Support Activity Panama....763 Naval Support Activity Panama City; Gulf of Mexico; restricted area. (a) The area. The area is... enforced by the Commanding Officer, Naval Support Activity, Panama City Florida, and such agencies as...

  18. Restricted dynamics of molecular hydrogen confined in activated carbon nanopores

    SciTech Connect

    Contescu, Cristian I; Saha, Dipendu; Gallego, Nidia C; Mamontov, Eugene; Kolesnikov, Alexander I; Bhat, Vinay V

    2012-01-01

    Quasi-elastic neutron scattering was used for characterization of dynamics of molecular hydrogen confined in narrow nanopores of two activated carbon materials: PFAC (derived from polyfurfuryl alcohol) and UMC (ultramicroporous carbon). Fast, but incomplete ortho-para conversion was observed at 10 K, suggesting that scattering originates from the fraction of unconverted ortho isomer which is rotation-hindered because of confinement in nanopores. Hydrogen molecules entrapped in narrow nanopores (<7 ) were immobile below 22-25 K. Mobility increased rapidly with temperature above this threshold, which is 8 K higher than the melting point of bulk hydrogen. Diffusion obeyed fixed-jump length mechanism, indistinguishable between 2D and 3D processes. Thermal activation of diffusion was characterized between ~22 and 37 K, and structure-dependent differences were found between the two carbons. Activation energy of diffusion was higher than that of bulk solid hydrogen. Classical notions of liquid and solid do not longer apply for H2 confined in narrow nanopores.

  19. 33 CFR 334.761 - Naval Support Activity Panama City; St. Andrews Bay; restricted areas.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... City; St. Andrews Bay; restricted areas. 334.761 Section 334.761 Navigation and Navigable Waters CORPS... REGULATIONS § 334.761 Naval Support Activity Panama City; St. Andrews Bay; restricted areas. (a) The areas—(1... waterline to 30°09′57.5″ N, 085°44′37″ W; then northerly to point of origin. (2) Area BA-1. The area...

  20. 33 CFR 334.761 - Naval Support Activity Panama City; St. Andrews Bay; restricted areas.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... City; St. Andrews Bay; restricted areas. 334.761 Section 334.761 Navigation and Navigable Waters CORPS... REGULATIONS § 334.761 Naval Support Activity Panama City; St. Andrews Bay; restricted areas. (a) The areas—(1... waterline to 30°09′57.5″ N, 085°44′37″ W; then northerly to point of origin. (2) Area BA-1. The area...

  1. [Is restriction of physical activity indicated in the prevention of retinal detachment?].

    PubMed

    Karel, I

    1993-06-01

    The author evaluates the importance of different vitreoretinal factors and the role of indirect injury in the pathogenesis of detachment of the retina/DR/and holds the following view as regards subjects inclined to pursue physical activity. Numerous and frequent vitreoretinal risk factors are a forecast of DR only in a small fraction of patients. Indirect injury is not recognized as a cause of DR. Risk factors incl. medium-grade and high-grade myopia are not an indication for restriction of physical activity nor for Caesarean section in pregnant women. Restriction of physical activity acts as a psychic trauma and does not prevent the development of DR. PMID:8348645

  2. 5 CFR 7001.102 - Restrictions on outside employment and business activities.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ..., including 5 CFR part 2635, which includes, among other provisions, the principle stated at 5 CFR 2635.101(b... business activities. 7001.102 Section 7001.102 Administrative Personnel UNITED STATES POSTAL SERVICE... Restrictions on outside employment and business activities. (a) Prohibited outside employment and...

  3. 5 CFR 7001.102 - Restrictions on outside employment and business activities.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ..., including 5 CFR part 2635, which includes, among other provisions, the principle stated at 5 CFR 2635.101(b... business activities. 7001.102 Section 7001.102 Administrative Personnel UNITED STATES POSTAL SERVICE... Restrictions on outside employment and business activities. (a) Prohibited outside employment and...

  4. 5 CFR 7001.102 - Restrictions on outside employment and business activities.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ..., including 5 CFR part 2635, which includes, among other provisions, the principle stated at 5 CFR 2635.101(b... business activities. 7001.102 Section 7001.102 Administrative Personnel UNITED STATES POSTAL SERVICE... Restrictions on outside employment and business activities. (a) Prohibited outside employment and...

  5. 5 CFR 7001.102 - Restrictions on outside employment and business activities.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ..., including 5 CFR part 2635, which includes, among other provisions, the principle stated at 5 CFR 2635.101(b... business activities. 7001.102 Section 7001.102 Administrative Personnel UNITED STATES POSTAL SERVICE... Restrictions on outside employment and business activities. (a) Prohibited outside employment and...

  6. The ribonuclease activity of SAMHD1 is required for HIV-1 restriction

    PubMed Central

    Ryoo, Jeongmin; Choi, Jongsu; Oh, Changhoon; Kim, Sungchul; Seo, Minji; Kim, Seokyoung; Seo, Daekwan; Kim, Jongkyu; White, Tommy E.; Brandariz-Nunez, Alberto; Diaz-Griffero, Felipe; Yun, Cheol-Heui; Hollenbaugh, Joseph A.; Kim, Baek; Baek, Daehyun

    2015-01-01

    The HIV-1 restriction factor SAMHD11,2 is proposed to inhibit HIV-1 replication by depleting the intracellular dNTP pool3-5. However, the phosphorylation of SAMHD1 regulates its ability to restrict HIV-1 without decreasing cellular dNTP levels6-8, which is not consistent with a role for SAMHD1 dNTPase activity in HIV-1 restriction. Here, we show that SAMHD1 possesses RNase activity and that the RNase but not the dNTPase function is essential for HIV-1 restriction. By enzymatically characterizing Aicardi-Goutières syndrome (AGS)-associated SAMHD1 mutations and mutations in the allosteric dGTP-binding site of SAMHD1, we identify SAMHD1 mutants that are RNase-positive but dNTPase-negative (SAMHD1D137N) or RNase-negative but dNTPase-positive (SAMHD1Q548A). The allosteric mutant SAMHD1D137N is able to restrict HIV-1 infection, whereas the AGS mutant SAMHD1Q548A is defective for HIV-1 restriction. SAMHD1 associates with HIV-1 RNA and degrades it during the early phases of infection. SAMHD1 silencing in macrophages and CD4+ T cells from healthy donors increases HIV-1 RNA stability, rendering the cells permissive for HIV-1 infection. Furthermore, the phosphorylation of SAMHD1 at T592 negatively regulates its RNase activity in vivo and impedes HIV-1 restriction. Our results reveal that the RNase activity of SAMHD1 is responsible for preventing HIV-1 infection by directly degrading the HIV-1 RNA. PMID:25038827

  7. Effects of Experimental Sleep Restriction on Caloric Intake and Activity Energy Expenditure

    PubMed Central

    Calvin, Andrew D.; Carter, Rickey E.; Adachi, Taro; G. Macedo, Paula; Albuquerque, Felipe N.; van der Walt, Christelle; Bukartyk, Jan; Davison, Diane E.; Levine, James A.

    2013-01-01

    Background: Epidemiologic studies link short sleep duration to obesity and weight gain. Insufficient sleep appears to alter circulating levels of the hormones leptin and ghrelin, which may promote appetite, although the effects of sleep restriction on caloric intake and energy expenditure are unclear. We sought to determine the effect of 8 days/8 nights of sleep restriction on caloric intake, activity energy expenditure, and circulating levels of leptin and ghrelin. Methods: We conducted a randomized study of usual sleep vs a sleep restriction of two-thirds of normal sleep time for 8 days/8 nights in a hospital-based clinical research unit. The main outcomes were caloric intake, activity energy expenditure, and circulating levels of leptin and ghrelin. Results: Caloric intake in the sleep-restricted group increased by +559 kcal/d (SD, 706 kcal/d, P = .006) and decreased in the control group by −118 kcal/d (SD, 386 kcal/d, P = .51) for a net change of +677 kcal/d (95% CI, 148-1,206 kcal/d; P = .014). Sleep restriction was not associated with changes in activity energy expenditure (P = .62). No change was seen in levels of leptin (P = .27) or ghrelin (P = .21). Conclusions: Sleep restriction was associated with an increase in caloric consumption with no change in activity energy expenditure or leptin and ghrelin concentrations. Increased caloric intake without any accompanying increase in energy expenditure may contribute to obesity in people who are exposed to long-term sleep restriction. Trial Registration: ClinicalTrials.gov; No.: NCT01334788; URL: www.clinicaltrials.gov PMID:23392199

  8. A dual active-restrictive approach to incorporating environmental flow targets into existing reservoir operation rules

    NASA Astrophysics Data System (ADS)

    Shiau, Jenq-Tzong; Wu, Fu-Chun

    2010-08-01

    Environmental flow schemes may be implemented through active or restrictive strategies. The former may be applied via reservoir releases, and the latter can be executed by reducing water demands. We present a dual active-restrictive approach to devising the optimal reservoir operation rules that aim to secure off-stream water supplies while maximizing environmental benefits. For the active part, a multicomponent environmental flow target (including the minimum and monthly flows) is incorporated in the operation rules. For the restrictive counterpart, we use a novel demands partitioning and prioritizing (DPP) approach to reallocating the demands of various sectors. The DPP approach partitions the existing off-stream demand and newly incorporated environmental demand and reassembles the two as the first- and second-priority demands. Water is reallocated to each demand according to the ratios derived from the prioritized demands. The proposed approach is coupled with a multicriteria optimization framework to seek the optimal operation rules for the existing Feitsui Reservoir system (Taiwan) under various scenarios. The best overall performance is achieved by an optimal dual strategy whose operational parameters are all determined by optimization. The optimal environmental flow target may well be a top-priority constant base flow rather than the variable quantities. The active strategy would outperform the restrictive one. For the former, a top-priority base flow target is essential; for the latter, the off-stream demand can become vanishingly small in compensation for the eliminated base flow target, thus promoting the monthly flow target as nearly the top-priority demand. For either the active or restrictive strategy, a prioritized environmental flow demand would provide a path toward the optimal overall performance. A significantly improved overall performance over the existing operation rules is unlikely if the active and restrictive parameters are both favorable

  9. 13 CFR 120.828 - Minimum level of 504 loan activity and restrictions on portfolio concentrations.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 13 Business Credit and Assistance 1 2012-01-01 2012-01-01 false Minimum level of 504 loan activity and restrictions on portfolio concentrations. 120.828 Section 120.828 Business Credit and Assistance... concentrations. (a) A CDC is required to receive SBA approval of at least four 504 loan approvals during...

  10. 13 CFR 120.828 - Minimum level of 504 loan activity and restrictions on portfolio concentrations.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 13 Business Credit and Assistance 1 2014-01-01 2014-01-01 false Minimum level of 504 loan activity and restrictions on portfolio concentrations. 120.828 Section 120.828 Business Credit and Assistance... concentrations. (a) A CDC is required to receive SBA approval of at least four 504 loan approvals during...

  11. 13 CFR 120.828 - Minimum level of 504 loan activity and restrictions on portfolio concentrations.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 13 Business Credit and Assistance 1 2013-01-01 2013-01-01 false Minimum level of 504 loan activity and restrictions on portfolio concentrations. 120.828 Section 120.828 Business Credit and Assistance... concentrations. (a) A CDC is required to receive SBA approval of at least four 504 loan approvals during...

  12. 13 CFR 120.828 - Minimum level of 504 loan activity and restrictions on portfolio concentrations.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 13 Business Credit and Assistance 1 2011-01-01 2011-01-01 false Minimum level of 504 loan activity and restrictions on portfolio concentrations. 120.828 Section 120.828 Business Credit and Assistance... concentrations. (a) A CDC is required to receive SBA approval of at least four 504 loan approvals during...

  13. 13 CFR 120.828 - Minimum level of 504 loan activity and restrictions on portfolio concentrations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 13 Business Credit and Assistance 1 2010-01-01 2010-01-01 false Minimum level of 504 loan activity and restrictions on portfolio concentrations. 120.828 Section 120.828 Business Credit and Assistance SMALL BUSINESS ADMINISTRATION BUSINESS LOANS Development Company Loan Program (504) Requirements for Cdc Certification and Operation §...

  14. Korean Children's Evaluation of Parental Restrictions Regarding Gender-Stereotypic Peer Activities

    ERIC Educational Resources Information Center

    Park, Yoonjung; Lee-Kim, Jennie; Killen, Melanie; Park, Kyoungja; Kim, Jihyun

    2012-01-01

    Korean children's evaluations of parental restrictions of children's activities based on gender stereotypic expectations were investigated. Third and sixth grade Korean (N = 128) children evaluated scenarios in which a boy or girl desired to play ballet or soccer. Participants used stereotypes to support children's desires to play…

  15. Restrictive pattern on spirometry: association with cardiovascular risk and level of physical activity in asymptomatic adults

    PubMed Central

    Sperandio, Evandro Fornias; Arantes, Rodolfo Leite; Matheus, Agatha Caveda; da Silva, Rodrigo Pereira; Lauria, Vinícius Tonon; Romiti, Marcello; Gagliardi, Antônio Ricardo de Toledo; Dourado, Victor Zuniga

    2016-01-01

    Objective : To determine whether a restrictive pattern on spirometry is associated with the level of physical activity in daily life (PADL), as well as with cardiovascular disease (CVD) risk factors, in asymptomatic adults. Methods : A total of 374 participants (mean age, 41 ± 14 years) underwent spirometry, which included the determination of FVC and FEV1. A restrictive pattern on spirometry was defined as an FEV1/FVC ratio > 0.7 and an FVC < 80% of the predicted value. After conducting demographic, anthropometric, and CVD risk assessments, we evaluated body composition, muscle function, and postural balance, as well as performing cardiopulmonary exercise testing and administering the six-minute walk test. The PADL was quantified with a triaxial accelerometer. Results : A restrictive pattern on spirometry was found in 10% of the subjects. After multivariate logistic regression, adjusted for confounders (PADL and cardiorespiratory fitness), the following variables retained significance (OR; 95% CI) as predictors of a restrictive pattern: systemic arterial hypertension (17.5; 1.65-184.8), smoking (11.6; 1.56-87.5), physical inactivity (8.1; 1.43-46.4), larger center-of-pressure area while standing on a force platform (1.34; 1.05-1.71); and dyslipidemia (1.89; 1.12-1.98). Conclusions : A restrictive pattern on spirometry appears to be common in asymptomatic adults. We found that CVD risk factors, especially systemic arterial hypertension, smoking, and physical inactivity, were directly associated with a restrictive pattern, even when the analysis was adjusted for PADL and cardiorespiratory fitness. Longitudinal studies are needed in order to improve understanding of the etiology of a restrictive pattern as well as to aid in the design of preventive strategies. PMID:26982037

  16. Activity restriction and the mechanistic basis for extinctions under climate warming.

    PubMed

    R Kearney, Michael

    2013-12-01

    Correlative analyses predict that anthropogenic climate warming will cause widespread extinction but the nature and generality of the underlying mechanisms is unclear. Warming-induced activity restriction has been proposed as a general explanatory mechanism for recent population extinctions in lizards, and has been used to forecast future extinction. Here, I test this hypothesis using globally applied biophysical calculations of the effects of warming and shade reduction on potential activity time and whole-life-cycle energy budgets. These 'thermodynamic niche' analyses show that activity restriction from climate warming is unlikely to provide a general explanation of recent extinctions, and that loss of shade is viable alternative explanation. Climate warming could cause population declines, even under increased activity potential, through joint impacts on fecundity and mortality rates. However, such responses depend strongly on behaviour, habitat (shade, food) and life history, all of which should be explicitly incorporated in mechanistic forecasts of extinction risk under climate change. PMID:24118740

  17. Inquiry-Based Experiments for Large-Scale Introduction to PCR and Restriction Enzyme Digests

    ERIC Educational Resources Information Center

    Johanson, Kelly E.; Watt, Terry J.

    2015-01-01

    Polymerase chain reaction and restriction endonuclease digest are important techniques that should be included in all Biochemistry and Molecular Biology laboratory curriculums. These techniques are frequently taught at an advanced level, requiring many hours of student and faculty time. Here we present two inquiry-based experiments that are…

  18. The effects of graded levels of calorie restriction: V. Impact of short term calorie and protein restriction on physical activity in the C57BL/6 mouse

    PubMed Central

    Mitchell, Sharon E.; Delville, Camille; Konstantopedos, Penelope; Derous, Davina; Green, Cara L.; Wang, Yingchun; Han, Jing-Dong J.; Promislow, Daniel E.L.; Douglas, Alex; Chen, Luonan; Lusseau, David; Speakman, John R.

    2016-01-01

    Calorie restriction (CR) delays the onset of age-related disease and extends lifespan in a number of species. When faced with reduced energy supply animals need to lower energy demands, which may be achieved in part by reducing physical activity (PA). We monitored changes in PA using implanted transmitters in male C57BL/6 mice in response to graded levels of CR (10 to 40%) or matched levels of graded protein restriction (PR) for 3 months. Mice were fed at lights out and ad libitum controls were limited to dark-phase feeding (12AL) or 24hr/day. Total daily PA declined in a non-linear manner over the first 30 days of CR or PR, remaining stable thereafter. Total daily PA was not related to the level of CR or PR. Total daily PA over the last 20 days of restriction was related to circulating leptin, insulin, tumor necrosis factor-α (TNF-α) and insulin-like growth factor (IGF)-1 levels, measured after 3 months. Mice under restriction showed a high level of activity in the 2hrs before feeding (food anticipatory activity: FAA). FAA followed a complex pattern, peaking around day 20, falling on ∼day 37 then increasing again. FAA was also positively related to the level of restriction and inversely to leptin, insulin, TNF-α and IGF-1. Non-FAA, in contrast, declined over the period of restriction, generally more so in mice under greater restriction, thereby offsetting to some extent the increase in FAA. Mice under PR displayed no changes in PA over time or in comparison to 12AL, and showed no increase in FAA. PMID:27007156

  19. The PML gene is linked to a megabase-scale insertion/deletion restriction fragment length polymorphism

    SciTech Connect

    Goy, A.; Xiao, Y.H.; Passalaris, T.

    1995-03-20

    The PML gene located on chromosome band 15q22 is involved with the RAR{alpha} locus (17q21) in a balanced reciprocal translocation uniquely observed in acute promyelocytic leukemia. Physical mapping studies by pulsed-field gel electrophoresis revealed that the PML gene is flanked by two CpG islands that are separated by a variable distance in normal individuals. Several lines of evidence demonstrate that this is the consequence of a large insertion/deletion polymorphism linked to the PML locus: (1) overlapping fragments obtained with a variety of rare-cutting restriction enzymes demonstrated the same variability in distance between the flanking CpG islands; (2) mapping with restriction enzymes insensitive to CpG methylation confirmed that the findings were not a consequence of variable methylation of CpG dinucleotides; (3) the polymorphism followed a Mendelian inheritance pattern. This polymorphism is localized 3{prime} to the PML locus. There are five common alleles, described on the basis of BssHII fragments, ranging from 220 to 350 kb with increments of approximately 30 kb between alleles. Both heterozygous (61%) and homozygous (391%) patterns were observed in normal individuals. Mega-base-scale insertion/deletion restriction fragment length polymorphisms are very rare and have been described initially in the context of multigene families. Such structures have been also reported as likely regions of genetic instability. High-resolution restriction mapping of this particular structure linked to the PML locus is underway. 47 refs., 4 figs., 1 tab.

  20. Interplay of Notch and FGF signaling restricts cell fate and MAPK activation in the Drosophila trachea.

    PubMed

    Ikeya, T; Hayashi, S

    1999-10-01

    The patterned branching in the Drosophila tracheal system is triggered by the FGF-like ligand Branchless that activates a receptor tyrosine kinase Breathless and the MAP kinase pathway. A single fusion cell at the tip of each fusion branch expresses the zinc-finger gene escargot, leads branch migration in a stereotypical pattern and contacts with another fusion cell to mediate fusion of the branches. A high level of MAP kinase activation is also limited to the tip of the branches. Restriction of such cell specialization events to the tip is essential for tracheal tubulogenesis. Here we show that Notch signaling plays crucial roles in the singling out process of the fusion cell. We found that Notch is activated in tracheal cells by Branchless signaling through stimulation of &Dgr; expression at the tip of tracheal branches and that activated Notch represses the fate of the fusion cell. In addition, Notch is required to restrict activation of MAP kinase to the tip of the branches, in part through the negative regulation of Branchless expression. Notch-mediated lateral inhibition in sending and receiving cells is thus essential to restrict the inductive influence of Branchless on the tracheal tubulogenesis. PMID:10498681

  1. Inquiry-based experiments for large-scale introduction to PCR and restriction enzyme digests.

    PubMed

    Johanson, Kelly E; Watt, Terry J

    2015-01-01

    Polymerase chain reaction and restriction endonuclease digest are important techniques that should be included in all Biochemistry and Molecular Biology laboratory curriculums. These techniques are frequently taught at an advanced level, requiring many hours of student and faculty time. Here we present two inquiry-based experiments that are designed for introductory laboratory courses and combine both techniques. In both approaches, students must determine the identity of an unknown DNA sequence, either a gene sequence or a primer sequence, based on a combination of PCR product size and restriction digest pattern. The experimental design is flexible, and can be adapted based on available instructor preparation time and resources, and both approaches can accommodate large numbers of students. We implemented these experiments in our courses with a combined total of 584 students and have an 85% success rate. Overall, students demonstrated an increase in their understanding of the experimental topics, ability to interpret the resulting data, and proficiency in general laboratory skills. PMID:26503481

  2. Large scale optimization of beam weights under dose-volume restrictions.

    PubMed

    Langer, M; Brown, R; Urie, M; Leong, J; Stracher, M; Shapiro, J

    1990-04-01

    The problem of choosing weights for beams in a multifield plan which maximizes tumor dose under conditions that recognize the volume dependence of organ tolerance to radiation is considered, and its solution described. Structures are modelled as collections of discrete points, and the weighting problem described as a combinatorial linear program (LP). The combinatorial LP is solved as a mixed 0/1 integer program with appropriate restrictions on normal tissue dose. The method is illustrated through the assignment of weights to a set of 10 beams incident on a pelvic target. Dose-volume restrictions are placed on surrounding bowel, bladder, and rectum, and a limit placed on tumor dose inhomogeneity. Different tolerance restrictions are examined, so that the sensitivity of the target dose to changes in the normal tissue constraints may be explored. It is shown that the distributions obtained satisfy the posed constraints. The technique permits formal solution of the optimization problem, in a time short enough to meet the needs of treatment planners. PMID:2323977

  3. Mouse Activity across Time Scales: Fractal Scenarios

    PubMed Central

    Lima, G. Z. dos Santos; Lobão-Soares, B.; do Nascimento, G. C.; França, Arthur S. C.; Muratori, L.; Ribeiro, S.; Corso, G.

    2014-01-01

    In this work we devise a classification of mouse activity patterns based on accelerometer data using Detrended Fluctuation Analysis. We use two characteristic mouse behavioural states as benchmarks in this study: waking in free activity and slow-wave sleep (SWS). In both situations we find roughly the same pattern: for short time intervals we observe high correlation in activity - a typical 1/f complex pattern - while for large time intervals there is anti-correlation. High correlation of short intervals ( to : waking state and to : SWS) is related to highly coordinated muscle activity. In the waking state we associate high correlation both to muscle activity and to mouse stereotyped movements (grooming, waking, etc.). On the other side, the observed anti-correlation over large time scales ( to : waking state and to : SWS) during SWS appears related to a feedback autonomic response. The transition from correlated regime at short scales to an anti-correlated regime at large scales during SWS is given by the respiratory cycle interval, while during the waking state this transition occurs at the time scale corresponding to the duration of the stereotyped mouse movements. Furthermore, we find that the waking state is characterized by longer time scales than SWS and by a softer transition from correlation to anti-correlation. Moreover, this soft transition in the waking state encompass a behavioural time scale window that gives rise to a multifractal pattern. We believe that the observed multifractality in mouse activity is formed by the integration of several stereotyped movements each one with a characteristic time correlation. Finally, we compare scaling properties of body acceleration fluctuation time series during sleep and wake periods for healthy mice. Interestingly, differences between sleep and wake in the scaling exponents are comparable to previous works regarding human heartbeat. Complementarily, the nature of these sleep-wake dynamics could lead to a better

  4. 33 CFR 334.762 - Naval Support Activity Panama City; North Bay and West Bay; restricted areas.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... City; North Bay and West Bay; restricted areas. 334.762 Section 334.762 Navigation and Navigable Waters... REGULATIONS § 334.762 Naval Support Activity Panama City; North Bay and West Bay; restricted areas. (a) The..., Naval Support Activity, Panama City Florida, and such agencies as he/she may designate....

  5. 33 CFR 334.762 - Naval Support Activity Panama City; North Bay and West Bay; restricted areas.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... City; North Bay and West Bay; restricted areas. 334.762 Section 334.762 Navigation and Navigable Waters... REGULATIONS § 334.762 Naval Support Activity Panama City; North Bay and West Bay; restricted areas. (a) The..., Naval Support Activity, Panama City Florida, and such agencies as he/she may designate....

  6. 33 CFR 334.762 - Naval Support Activity Panama City; North Bay and West Bay; restricted areas.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... City; North Bay and West Bay; restricted areas. 334.762 Section 334.762 Navigation and Navigable Waters... REGULATIONS § 334.762 Naval Support Activity Panama City; North Bay and West Bay; restricted areas. (a) The..., Naval Support Activity, Panama City Florida, and such agencies as he/she may designate....

  7. 33 CFR 334.762 - Naval Support Activity Panama City; North Bay and West Bay; restricted areas.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... City; North Bay and West Bay; restricted areas. 334.762 Section 334.762 Navigation and Navigable Waters... REGULATIONS § 334.762 Naval Support Activity Panama City; North Bay and West Bay; restricted areas. (a) The..., Naval Support Activity, Panama City Florida, and such agencies as he/she may designate....

  8. 33 CFR 334.762 - Naval Support Activity Panama City; North Bay and West Bay; restricted areas.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... City; North Bay and West Bay; restricted areas. 334.762 Section 334.762 Navigation and Navigable Waters... REGULATIONS § 334.762 Naval Support Activity Panama City; North Bay and West Bay; restricted areas. (a) The..., Naval Support Activity, Panama City Florida, and such agencies as he/she may designate....

  9. Specific induction of endogenous viral restriction factors using CRISPR/Cas-derived transcriptional activators

    PubMed Central

    Bogerd, Hal P.; Kornepati, Anand V. R.; Marshall, Joy B.; Kennedy, Edward M.; Cullen, Bryan R.

    2015-01-01

    Whereas several mammalian proteins can restrict the replication of HIV-1 and other viruses, these are often not expressed in relevant target cells. A potential method to inhibit viral replication might therefore be to use synthetic transcription factors to induce restriction factor expression. In particular, mutants of the RNA-guided DNA binding protein Cas9 that have lost their DNA cleavage activity could be used to recruit transcription activation domains to specific promoters. However, initial experiments revealed only weak activation unless multiple promoter-specific single guide RNAs (sgRNAs) were used. Recently, the recruitment of multiple transcription activation domains by a single sgRNA, modified to contain MS2-derived stem loops that recruit fusion proteins consisting of the MS2 coat protein linked to transcription activation domains, was reported to induce otherwise silent cellular genes. Here, we demonstrate that such “synergistic activation mediators” can induce the expression of two restriction factors, APOBEC3G (A3G) and APOBEC3B (A3B), in human cells that normally lack these proteins. We observed modest activation of endogenous A3G or A3B expression using single sgRNAs but high expression when two sgRNAs were used. Whereas the induced A3G and A3B proteins both blocked infection by an HIV-1 variant lacking a functional vif gene by inducing extensive dC-to-dU editing, only the induced A3B protein inhibited wild-type HIV-1. These data demonstrate that Cas9-derived transcriptional activators have the potential to be used for screens for endogenous genes that affect virus replication and raise the possibility that synthetic transcription factors might prove clinically useful if efficient delivery mechanisms could be developed. PMID:26668372

  10. Specific induction of endogenous viral restriction factors using CRISPR/Cas-derived transcriptional activators.

    PubMed

    Bogerd, Hal P; Kornepati, Anand V R; Marshall, Joy B; Kennedy, Edward M; Cullen, Bryan R

    2015-12-29

    Whereas several mammalian proteins can restrict the replication of HIV-1 and other viruses, these are often not expressed in relevant target cells. A potential method to inhibit viral replication might therefore be to use synthetic transcription factors to induce restriction factor expression. In particular, mutants of the RNA-guided DNA binding protein Cas9 that have lost their DNA cleavage activity could be used to recruit transcription activation domains to specific promoters. However, initial experiments revealed only weak activation unless multiple promoter-specific single guide RNAs (sgRNAs) were used. Recently, the recruitment of multiple transcription activation domains by a single sgRNA, modified to contain MS2-derived stem loops that recruit fusion proteins consisting of the MS2 coat protein linked to transcription activation domains, was reported to induce otherwise silent cellular genes. Here, we demonstrate that such "synergistic activation mediators" can induce the expression of two restriction factors, APOBEC3G (A3G) and APOBEC3B (A3B), in human cells that normally lack these proteins. We observed modest activation of endogenous A3G or A3B expression using single sgRNAs but high expression when two sgRNAs were used. Whereas the induced A3G and A3B proteins both blocked infection by an HIV-1 variant lacking a functional vif gene by inducing extensive dC-to-dU editing, only the induced A3B protein inhibited wild-type HIV-1. These data demonstrate that Cas9-derived transcriptional activators have the potential to be used for screens for endogenous genes that affect virus replication and raise the possibility that synthetic transcription factors might prove clinically useful if efficient delivery mechanisms could be developed. PMID:26668372

  11. Restricted psychological horizon in active methamphetamine users: future, past, probability, and social discounting

    PubMed Central

    Yi, Richard; Carter, Anne E.; Landes, Reid D.

    2014-01-01

    Methamphetamine users (MAU) exhibit an exaggerated bias for immediate rewards that reflects a restricted time horizon, where outcomes in the future are excessively discounted. An accumulating literature indicates that time in the future shares features with other dimensions of psychological distances including time in the past probability, and social distance, suggesting that bias for immediacy may be reducible to a more general restriction of psychological horizon. The purpose of the present study was to explore generalized restricted psychological horizon in active MAU by assessing future, past, probability, and social discounting. Compared with nonusing controls, MAU preferred psychologically proximal outcomes, resulting in higher rates for all types of discounting, which supports the conceptualization that MAU insufficiently integrate outcomes of psychological distance (i.e. in the future, the past, probabilistic, for others) into the valuation of current behavioral alternatives. The present results are suggestive of a more fundamental process of problematic decision-making associated with methamphetamine use, indicating the necessity of more comprehensive approaches to address the generalized limitations of restricted psychological horizon. PMID:22743602

  12. Exercise performance, core temperature, and metabolism after prolonged restricted activity and retraining in dogs

    NASA Technical Reports Server (NTRS)

    Nazar, K.; Greenleaf, J. E.; Pohoska, E.; Turlejska, E.; Kaciuba-Uscilko, H.; Kozlowski, S.

    1992-01-01

    Physiological effects of restricted activity (RA) and subsequent retraining have been studied. Ten male mongrel dogs performed a submaximal exercise endurance test on a treadmill during kennel control, after 8 weeks of cage confinement and after eight weeks of retraining using the same treadmill protocol 1 h/d for 6 d/week. Data obtained show that RA reduces exercise endurance, the effectiveness of exercise thermoregulation, muscle glycogen stores, and the lipolytic response to exercise and to noradrenaline stimulation.

  13. Creation of chimeric human/rabbit APOBEC1 with HIV-1 restriction and DNA mutation activities.

    PubMed

    Ikeda, Terumasa; Ong, Eugene Boon Beng; Watanabe, Nobumoto; Sakaguchi, Nobuo; Maeda, Kazuhiko; Koito, Atsushi

    2016-01-01

    APOBEC1 (A1) proteins from lagomorphs and rodents have deaminase-dependent restriction activity against HIV-1, whereas human A1 exerts a negligible effect. To investigate these differences in the restriction of HIV-1 by A1 proteins, a series of chimeric proteins combining rabbit and human A1s was constructed. Homology models of the A1s indicated that their activities derive from functional domains that likely act in tandem through a dimeric interface. The C-terminal region containing the leucine-rich motif and the dimerization domains of rabbit A1 is important for its anti-HIV-1 activity. The A1 chimeras with strong anti-HIV-1 activity were incorporated into virions more efficiently than those without anti-HIV-1 activity, and exhibited potent DNA-mutator activity. Therefore, the C-terminal region of rabbit A1 is involved in both its packaging into the HIV-1 virion and its deamination activity against both viral cDNA and genomic RNA. This study identifies the novel molecular mechanism underlying the target specificity of A1. PMID:26738439

  14. Creation of chimeric human/rabbit APOBEC1 with HIV-1 restriction and DNA mutation activities

    NASA Astrophysics Data System (ADS)

    Ikeda, Terumasa; Ong, Eugene Boon Beng; Watanabe, Nobumoto; Sakaguchi, Nobuo; Maeda, Kazuhiko; Koito, Atsushi

    2016-01-01

    APOBEC1 (A1) proteins from lagomorphs and rodents have deaminase-dependent restriction activity against HIV-1, whereas human A1 exerts a negligible effect. To investigate these differences in the restriction of HIV-1 by A1 proteins, a series of chimeric proteins combining rabbit and human A1s was constructed. Homology models of the A1s indicated that their activities derive from functional domains that likely act in tandem through a dimeric interface. The C-terminal region containing the leucine-rich motif and the dimerization domains of rabbit A1 is important for its anti-HIV-1 activity. The A1 chimeras with strong anti-HIV-1 activity were incorporated into virions more efficiently than those without anti-HIV-1 activity, and exhibited potent DNA-mutator activity. Therefore, the C-terminal region of rabbit A1 is involved in both its packaging into the HIV-1 virion and its deamination activity against both viral cDNA and genomic RNA. This study identifies the novel molecular mechanism underlying the target specificity of A1.

  15. Creation of chimeric human/rabbit APOBEC1 with HIV-1 restriction and DNA mutation activities

    PubMed Central

    Ikeda, Terumasa; Ong, Eugene Boon Beng; Watanabe, Nobumoto; Sakaguchi, Nobuo; Maeda, Kazuhiko; Koito, Atsushi

    2016-01-01

    APOBEC1 (A1) proteins from lagomorphs and rodents have deaminase-dependent restriction activity against HIV-1, whereas human A1 exerts a negligible effect. To investigate these differences in the restriction of HIV-1 by A1 proteins, a series of chimeric proteins combining rabbit and human A1s was constructed. Homology models of the A1s indicated that their activities derive from functional domains that likely act in tandem through a dimeric interface. The C-terminal region containing the leucine-rich motif and the dimerization domains of rabbit A1 is important for its anti-HIV-1 activity. The A1 chimeras with strong anti-HIV-1 activity were incorporated into virions more efficiently than those without anti-HIV-1 activity, and exhibited potent DNA-mutator activity. Therefore, the C-terminal region of rabbit A1 is involved in both its packaging into the HIV-1 virion and its deamination activity against both viral cDNA and genomic RNA. This study identifies the novel molecular mechanism underlying the target specificity of A1. PMID:26738439

  16. Chronic hyperhydration and hematological changes in trained subjects during prolonged restriction of motor activity

    NASA Astrophysics Data System (ADS)

    Zorbas, Yan G.; Yaroshenko, Michael N.; Federenko, Youri F.

    1995-08-01

    The objective of this investigation was to evaluate the effect of a daily intake of fluid and salt supplementation (FSS) on the hemoglobin content of endurance trained athletes during hypokinesia (decreased number of steps from 10,000 to 3000 steps per day). The studies were performed on 30 long-distance runners who had a VO 2max average of 66 ml kg -1 min -1 and were in the age range of 19-24 years. Prior to their exposure to hypokinesia (HK) of 364 days, all volunteers were on an average of 10,000 steps per day. All volunteers were divided into three equal groups: the first group underwent normal ambulatory life (control subjects), the second group was kept under continuous restriction of motor activity (hypokinetic subjects) and the third group was placed under continuous restriction of motor activity and consumed 26 ml water kg -1 body weight daily and 0.1 g sodium chloride kg -1 body weight in the form of supplementation (hyperhydrated subjects). For simulation of the hypokinetic effect, the number of steps taken per day by the second and third groups of volunteers was restricted to an average of 3000. During the hypokinetic period we determined reticulocytes (Rt), hemoglobin (Hb), hematocrit (Hct), plasma volume (PV), red blood cell (RBC) mass and VO 2max. In hyperhydrated volunteers the content of Hb and Hct decreased significantly, while PV, RBC mass and Rt count increased significantly. In hypokinetic volunteers Hb and Hct increased, while PV, RBC and Rt decreased significantly. It was concluded that chronic hyperhydration may be used to attentuate an increase in the Hb content of physically conditioned subjects during prolonged restriction of motor activity.

  17. HIPK2 restricts SIRT1 activity upon severe DNA damage by a phosphorylation-controlled mechanism.

    PubMed

    Conrad, E; Polonio-Vallon, T; Meister, M; Matt, S; Bitomsky, N; Herbel, C; Liebl, M; Greiner, V; Kriznik, B; Schumacher, S; Krieghoff-Henning, E; Hofmann, T G

    2016-01-01

    Upon severe DNA damage a cellular signalling network initiates a cell death response through activating tumour suppressor p53 in association with promyelocytic leukaemia (PML) nuclear bodies. The deacetylase Sirtuin 1 (SIRT1) suppresses cell death after DNA damage by antagonizing p53 acetylation. To facilitate efficient p53 acetylation, SIRT1 function needs to be restricted. How SIRT1 activity is regulated under these conditions remains largely unclear. Here we provide evidence that SIRT1 activity is limited upon severe DNA damage through phosphorylation by the DNA damage-responsive kinase HIPK2. We found that DNA damage provokes interaction of SIRT1 and HIPK2, which phosphorylates SIRT1 at Serine 682 upon lethal damage. Furthermore, upon DNA damage SIRT1 and HIPK2 colocalize at PML nuclear bodies, and PML depletion abrogates DNA damage-induced SIRT1 Ser682 phosphorylation. We show that Ser682 phosphorylation inhibits SIRT1 activity and impacts on p53 acetylation, apoptotic p53 target gene expression and cell death. Mechanistically, we found that DNA damage-induced SIRT1 Ser682 phosphorylation provokes disruption of the complex between SIRT1 and its activator AROS. Our findings indicate that phosphorylation-dependent restriction of SIRT1 activity by HIPK2 shapes the p53 response. PMID:26113041

  18. HIPK2 restricts SIRT1 activity upon severe DNA damage by a phosphorylation-controlled mechanism

    PubMed Central

    Conrad, E; Polonio-Vallon, T; Meister, M; Matt, S; Bitomsky, N; Herbel, C; Liebl, M; Greiner, V; Kriznik, B; Schumacher, S; Krieghoff-Henning, E; Hofmann, T G

    2016-01-01

    Upon severe DNA damage a cellular signalling network initiates a cell death response through activating tumour suppressor p53 in association with promyelocytic leukaemia (PML) nuclear bodies. The deacetylase Sirtuin 1 (SIRT1) suppresses cell death after DNA damage by antagonizing p53 acetylation. To facilitate efficient p53 acetylation, SIRT1 function needs to be restricted. How SIRT1 activity is regulated under these conditions remains largely unclear. Here we provide evidence that SIRT1 activity is limited upon severe DNA damage through phosphorylation by the DNA damage-responsive kinase HIPK2. We found that DNA damage provokes interaction of SIRT1 and HIPK2, which phosphorylates SIRT1 at Serine 682 upon lethal damage. Furthermore, upon DNA damage SIRT1 and HIPK2 colocalize at PML nuclear bodies, and PML depletion abrogates DNA damage-induced SIRT1 Ser682 phosphorylation. We show that Ser682 phosphorylation inhibits SIRT1 activity and impacts on p53 acetylation, apoptotic p53 target gene expression and cell death. Mechanistically, we found that DNA damage-induced SIRT1 Ser682 phosphorylation provokes disruption of the complex between SIRT1 and its activator AROS. Our findings indicate that phosphorylation-dependent restriction of SIRT1 activity by HIPK2 shapes the p53 response. PMID:26113041

  19. Calorigenic effect of adrenaline in rats under conditions of restricted motor activity

    NASA Technical Reports Server (NTRS)

    Tomaszewska, L.; Kaciuba-Uscilko, H.; Kozlowski, S.

    1980-01-01

    In previous studies, it was demonstrated that long term restricted motor activity in rats induces a decrease in body weight, an increase in release of adrenaline, and a decrease in the release of noradrenaline with the urine, as well as a reduction in activity of the thymus gland and level of thyroxin in the blood. At the same time, a decrease was found in the internal body temperature that was accompanied by an increase in the rate of metabolism in the state of rest. An investigation is presented which attempts to clarify whether the calorigenic effect of adrenaline under conditions of increased metabolism in the period of immobility is exposed to changes.

  20. Psychometric Validation of the Self-Efficacy for Restricting Dietary Salt in Hemodialysis Scale

    PubMed Central

    Clark-Cutaia, Maya N.; Ren, Dianxu; Hoffman, Leslie A.; Snetselaar, Linda; Sevick, Mary Ann

    2014-01-01

    The development and progression of left ventricular hypertrophy is a consequence of multiple comorbid conditions associated with end-stage renal disease and large variations in interdialytic weight gains. The literature suggests that dietary sodium restriction alone significantly reduces interdialytic weight gains. A total of 124 hemodialysis participants in an ongoing randomized control trial participated in the validation in which psychometric properties of a self-efficacy survey were a secondary analysis. We evaluated the internal consistency, construct validity, and convergent validity of the instrument. The overall Cronbach α was 0.93. Three factors extracted explain 67.8% of the variance of the white and African American participants. The Self-Efficacy Survey has adequate internal consistency and construct and convergent validity. Future research is needed to evaluate the stability and discriminant validity of the instrument. PMID:26213444

  1. Restricted use of ET as an indicator of soil moisture: Limitation of Observation Scale or Process Scale?

    NASA Astrophysics Data System (ADS)

    Gaur, N.; Mohanty, B. P.

    2010-12-01

    Evapotranspiration (ET) plays a vital role in the water balance cycle by altering the total available soil moisture. This study explores the utility of using ET, estimated at two different scales from 2 different sensors (MASTER, 7.5m and LANDSAT, 120m) as an indicator of the soil moisture content. The study area comprises of two irrigated almond orchards in Kern County, California and ET estimates were made using the simplified- surface energy balance index (S-SEBI) algorithm. It was found that in a row plantation, ET estimates from only the MASTER sensor which has a scale of observation comparable to spacing between the crops are good indicators of soil moisture. It is seen that this arises as a result of the difference in spatial resolutions or the ‘observation scale’ of the two sensors. The effect of using NDVI inputs in the same model from two different sensors at different scales has also been examined. The difference in bandwidths of the near infra red band in different sensors is a very important factor since it can change the reflectance signal from the plant canopy depending upon the water content and thus, affect the NDVI estimates. At a coarser scale NDVI becomes a better indicator of soil moisture differences.

  2. WRKY6 Transcription Factor Restricts Arsenate Uptake and Transposon Activation in Arabidopsis[W

    PubMed Central

    Castrillo, Gabriel; Sánchez-Bermejo, Eduardo; de Lorenzo, Laura; Crevillén, Pedro; Fraile-Escanciano, Ana; TC, Mohan; Mouriz, Alfonso; Catarecha, Pablo; Sobrino-Plata, Juan; Olsson, Sanna; Leo del Puerto, Yolanda; Mateos, Isabel; Rojo, Enrique; Hernández, Luis E.; Jarillo, Jose A.; Piñeiro, Manuel; Paz-Ares, Javier; Leyva, Antonio

    2013-01-01

    Stress constantly challenges plant adaptation to the environment. Of all stress types, arsenic was a major threat during the early evolution of plants. The most prevalent chemical form of arsenic is arsenate, whose similarity to phosphate renders it easily incorporated into cells via the phosphate transporters. Here, we found that arsenate stress provokes a notable transposon burst in plants, in coordination with arsenate/phosphate transporter repression, which immediately restricts arsenate uptake. This repression was accompanied by delocalization of the phosphate transporter from the plasma membrane. When arsenate was removed, the system rapidly restored transcriptional expression and membrane localization of the transporter. We identify WRKY6 as an arsenate-responsive transcription factor that mediates arsenate/phosphate transporter gene expression and restricts arsenate-induced transposon activation. Plants therefore have a dual WRKY-dependent signaling mechanism that modulates arsenate uptake and transposon expression, providing a coordinated strategy for arsenate tolerance and transposon gene silencing. PMID:23922208

  3. Amplitude Scaling of Active Separation Control

    NASA Technical Reports Server (NTRS)

    Stalnov, Oksana; Seifert, Avraham

    2010-01-01

    Three existing and two new excitation magnitude scaling options for active separation control at Reynolds numbers below one Million. The physical background for the scaling options was discussed and their relevance was evaluated using two different sets of experimental data. For F+ approx. 1, 2D excitation: a) The traditional VR and C(mu) - do not scale the data. b) Only the Re*C(mu) is valid. This conclusion is also limited for positive lift increment.. For F+ > 10, 3D excitation, the Re corrected C(mu), the St corrected velocity ratio and the vorticity flux coefficient, all scale the amplitudes equally well. Therefore, the Reynolds weighted C(mu) is the preferred choice, relevant to both excitation modes. Incidence also considered, using Ue from local Cp.

  4. Development of the Occupational Activities Knee Scale.

    PubMed

    Styron, Joseph F; Singer, Mendel E; Barsoum, Wael K

    2010-06-01

    A primary concern of many knee surgery patients is their ability to return to work following surgery, but it is often difficult to predict the practicality of returning due to a job's unclear knee demands. A cross-sectional study of employed patients and general population participants was conducted. Study participants were asked if their job required nine separate tasks and if their job had low, moderate, or high physical demands. The relative risk of each task placing high demands on the knee was calculated, and those risk ratios were summated to calculate a scaled score. The scaled score accurately distinguishes the levels of job demands with each reported level of job demands having a significantly higher mean scaled score than the level below it (p < 0.0001). The Occupational Activities Knee Scale offers occupational and health care providers greater precision in comparing the physical requirements of jobs for knee surgery patients. PMID:21141686

  5. Live Scale Active Shooter Exercise: Lessons Learned

    ERIC Educational Resources Information Center

    Ervin, Randy

    2008-01-01

    On October 23, 2007, the Lake Land College Public Safety Department conducted a full-scale live exercise that simulated an active shooter and barricaded hostage. In this article, the author will emphasize what they learned, and how they intend to benefit from it. He will list the law enforcement issues and general issues they encountered, and then…

  6. Analysis of the restricting factors of laser countermeasure active detection technology

    NASA Astrophysics Data System (ADS)

    Zhang, Yufa; Sun, Xiaoquan

    2016-07-01

    The detection effect of laser active detection system is affected by various kinds of factors. In view of the application requirement of laser active detection, the influence factors for laser active detection are analyzed. The mathematical model of cat eye target detection distance has been built, influence of the parameters of laser detection system and the environment on detection range and the detection efficiency are analyzed. Various parameters constraint detection performance is simulated. The results show that the discovery distance of laser active detection is affected by the laser divergence angle, the incident angle and the visibility of the atmosphere. For a given detection range, the laser divergence angle and the detection efficiency are mutually restricted. Therefore, in view of specific application environment, it is necessary to select appropriate laser detection parameters to achieve optimal detection effect.

  7. Electrochemical biosensor modified with dsDNA monolayer for restriction enzyme activity determination.

    PubMed

    Zajda, Joanna; Górski, Łukasz; Malinowska, Elżbieta

    2016-06-01

    A simple and cost effective method for the determination of restriction endonuclease activity is presented. dsDNA immobilized at a gold electrode surface is used as the enzymatic substrate, and an external cationic redox probe is employed in voltammetric measurements for analytical signal generation. The assessment of enzyme activity is based on a decrease of a current signal derived from reduction of methylene blue which is present in the sample solution. For this reason, the covalent attachment of the label molecule is not required which significantly reduces costs of the analysis and simplifies the entire determination procedure. The influence of buffer components on utilized dsDNA/MCH monolayer stability and integrity is also verified. Electrochemical impedance spectroscopy measurements reveal that due to pinhole formation during enzyme activity measurement the presence of any surfactants should be avoided. Additionally, it is shown that the sensitivity of the electrochemical biosensor can be tuned by changing the restriction site location along the DNA length. Under optimal conditions the proposed biosensor exhibits a linear response toward PvuII activity within a range from 0.25 to 1.50 U/μL. PMID:26859430

  8. Recording of brain activity across spatial scales.

    PubMed

    Lewis, C M; Bosman, C A; Fries, P

    2015-06-01

    Brain activity reveals exquisite coordination across spatial scales, from local microcircuits to brain-wide networks. Understanding how the brain represents, transforms and communicates information requires simultaneous recordings from distributed nodes of whole brain networks with single-cell resolution. Realizing multi-site recordings from communicating populations is hampered by the need to isolate clusters of interacting cells, often on a day-to-day basis. Chronic implantation of multi-electrode arrays allows long-term tracking of activity. Lithography on thin films provides a means to produce arrays of variable resolution, a high degree of flexibility, and minimal tissue displacement. Sequential application of surface arrays to monitor activity across brain-wide networks and subsequent implantation of laminar arrays to target specific populations enables continual refinement of spatial scale while maintaining coverage. PMID:25544724

  9. Increasing cleavage specificity and activity of restriction endonuclease KpnI

    PubMed Central

    Vasu, Kommireddy; Nagamalleswari, Easa; Zahran, Mai; Imhof, Petra; Xu, Shuang-yong; Zhu, Zhenyu; Chan, Siu-Hong; Nagaraja, Valakunja

    2013-01-01

    Restriction enzyme KpnI is a HNH superfamily endonuclease requiring divalent metal ions for DNA cleavage but not for binding. The active site of KpnI can accommodate metal ions of different atomic radii for DNA cleavage. Although Mg2+ ion higher than 500 μM mediates promiscuous activity, Ca2+ suppresses the promiscuity and induces high cleavage fidelity. Here, we report that a conservative mutation of the metal-coordinating residue D148 to Glu results in the elimination of the Ca2+-mediated cleavage but imparting high cleavage fidelity with Mg2+. High cleavage fidelity of the mutant D148E is achieved through better discrimination of the target site at the binding and cleavage steps. Biochemical experiments and molecular dynamics simulations suggest that the mutation inhibits Ca2+-mediated cleavage activity by altering the geometry of the Ca2+-bound HNH active site. Although the D148E mutant reduces the specific activity of the enzyme, we identified a suppressor mutation that increases the turnover rate to restore the specific activity of the high fidelity mutant to the wild-type level. Our results show that active site plasticity in coordinating different metal ions is related to KpnI promiscuous activity, and tinkering the metal ion coordination is a plausible way to reduce promiscuous activity of metalloenzymes. PMID:23963701

  10. Constitutive activation of casein kinase 2 in glioblastomas: Absence of class restriction and broad therapeutic potential.

    PubMed

    Dubois, Nadege; Willems, Marie; Nguyen-Khac, Minh-Tuan; Kroonen, Jerome; Goffart, Nicolas; Deprez, Manuel; Bours, Vincent; Robe, Pierre A

    2016-06-01

    Casein kinase II contributes to the growth and survival of malignant gliomas and attracts increasing attention as a therapeutic target in these tumors. Several reports have suggested that this strategy might be most relevant for specific subgroups of patients, namely Verhaak's classical and TP53 wild-type tumors. Using kinase assays and microarray genetic profiling in a series of 27 proprietary fresh frozen surgical glioma samples, we showed that constitutive CK2 kinase activation is not restricted to tumors that present increased copy numbers or mRNA expression of its catalytic or regulatory subunits, and can result from a functional activation by various cytokines from the glioma microenvironment. Using corresponding primary tumor and human astrocyte cell cultures as well as glioma cell lines, we confirmed that CK2 inhibition is selectively toxic to malignant glial tumors, without any restriction to tumor class or to TP53 status. We finally showed that while the contribution of CK2 to the constitutive NF-κB hyperactivation in malignant gliomas is at best moderate, a delayed activation of NF-κB may associate with the therapeutic resistance of glioma cells to CK2 inhibition. PMID:27098015

  11. Conformationally restricted elongation factor G retains GTPase activity but is inactive in translocation on the ribosome.

    PubMed

    Peske, F; Matassova, N B; Savelsbergh, A; Rodnina, M V; Wintermeyer, W

    2000-08-01

    Elongation factor G (EF-G) from Escherichia coli is a large, five-domain GTPase that promotes tRNA translocation on the ribosome. Full activity requires GTP hydrolysis, suggesting that a conformational change of the factor is important for function. To restrict the intramolecular mobility, two cysteine residues were engineered into domains 1 and 5 of EF-G that spontaneously formed a disulfide cross-link. Cross-linked EF-G retained GTPase activity on the ribosome, whereas it was inactive in translocation as well as in turnover. Both activities were restored when the cross-link was reversed by reduction. These results strongly argue against a GTPase switch-type model of EF-G function and demonstrate that conformational mobility is an absolute requirement for EF-G function on the ribosome. PMID:10983996

  12. Commercial scale fabrication method for fabricating a gradient refractive-index rod: Overcoming volume shrinkage and chemical restrictions.

    PubMed

    Cho, Hansol; Son, Young Mok; Kim, Mu Gyeom; Ra, Byoung Joo; Park, Joon-Yong; Lee, Seung Hui; Choi, Jin Sung; Song, Min Young; Park, O Ok; Kim, Youn Cheol; Hwang, Jin Taek

    2006-10-01

    We report a fabrication method for a gradient refractive-index polymeric object from a binary comonomer system, regardless of the monomers' reactivity ratio and the molar volume criteria of gradient refractive-index development. To fabricate a large gradient refractive-index rod consisting of a methyl methacrylate and 2,2,3,3-tetrafluoropropyl methacrylate comonomer pair that has not been used for fabrication of a copolymer gradient refractive-index rod by previous conventional methods because of chemical restrictions in molar volume and reactivity ratio difference, we use the so-called successive UV polymerization in a controlled radial volume in conjunction with an automatic refill reactor. Simultaneously and automatically, the volume shrinkage problem, an inevitable shortcoming for the fabrication of a large polymeric object in a commercial production scale, is overcome and exploited. The theoretical features of the refractive-index profile generation of this method are also compared with those of conventional methods for which the chemical restrictions of monomers are crucial for the shape of a refractive-index profile. PMID:16983409

  13. Restrictions on two Higgs doublet models and CP violation at the unification scale

    SciTech Connect

    Athanasiu, G.G.

    1987-04-01

    Bounds on charged Higgs masses and couplings in models with two Higgs doublets are examined that came from CP violation in the neutral K system. Bounds on charged Higgs masses and couplings in two Higgs doublet models are also obtained from their effects on neutral-B-meson mixing. The bounds are found to be comparable to those obtained with additional assumptions from the neutral K system. The three generation phase invariant measure of CP violation is shown to satisfy a simple and solvable renormalization group equation. Its value is seen to fall by four to eight orders of magnitude between the weak and grand unification scales in the standard model, as well as in its two Higgs and supersymmetric extensions. (LEW)

  14. A novel measure of compulsive food restriction in anorexia nervosa: validation of the Self-Starvation Scale (SS).

    PubMed

    Godier, Lauren R; Park, Rebecca J

    2015-04-01

    The characteristic relentless self-starvation behaviour seen in Anorexia Nervosa (AN) has been described as evidence of compulsivity, with increasing suggestion of transdiagnostic parallels with addictive behaviour. There is a paucity of standardised self-report measures of compulsive behaviour in eating disorders (EDs). Measures that index the concept of compulsive self-starvation in AN are needed to explore the suggested parallels with addictions. With this aim a novel measure of self-starvation was developed (the Self-Starvation Scale, SS). 126 healthy participants, and 78 individuals with experience of AN, completed the new measure along with existing measures of eating disorder symptoms, anxiety and depression. Initial validation in the healthy sample indicated good reliability and construct validity, and incremental validity in predicting eating disorder symptoms. The psychometric properties of the SS scale were replicated in the AN sample. The ability of this scale to predict ED symptoms was particularly strong in individuals currently suffering from AN. These results suggest the SS may be a useful index of compulsive food restriction in AN. The concept of 'starvation dependence' in those with eating disorders, as a parallel with addiction, may be of clinical and theoretical importance. PMID:25528717

  15. Muscle mitochondrial density after exhaustive exercise in dogs - Prolonged restricted activity and retraining

    NASA Technical Reports Server (NTRS)

    Nazar, K.; Greenleaf, J. E.; Philpott, D.; Pohoska, E.; Olszewska, K.; Kaciuba-Uscilko, H.

    1993-01-01

    The effect of exhaustive treadmill exercise on mitochondrial density (MD) and ultrastructural changes in quadriceps femoris muscle was studied in 7 normal, healthy, male mongrel dogs before and after restricted activity (RA) and following a subsequent 2-month exercise retraining period. Mean time to exhaustion in the 2-month group decreased from 177 +/- 11 min before to 90 +/- 16 min after RA; retraining increased tolerance to 219 +/- 36 min above the pre-RA and 143 percent above the post-RA time. Post-RA exhaustion time in the 5-months group was 25 and 45 min. Muscle samples taken after RA showed abnormalities indicative of degeneration, which were reversed by retraining. Resting MD decreased from a control level of 27.8 percent to 14.7 percent and 16.3 percent, and was restored to 27.1 percent after retraining. Exhaustive exercise caused an increase in MD under control conditions and after RA, but not following retraining. Disruption of mitochondria after exercise was evident after 5-month confinement. Factors causing mitochondrial changes and eventually their disruption during exercise after restricted activity are not related as much to the state of fatigue as to the pre-exercise quality of the muscle modified by disease or training.

  16. Relationship between activity limitations and participation restriction in school-aged children with cerebral palsy

    PubMed Central

    Park, Eun-Young; Kim, Won-Ho

    2015-01-01

    [Purpose] This study investigated the relationship between activity limitation and participation restriction in school-aged children with cerebral palsy. [Subjects and Methods] Data were collected from 109 children with cerebral palsy aged 6–12 years. Activity limitations were assessed by using functional classification systems including the Korean-Gross Motor Function Classification System, the Korean-Manual Ability Classification System, and the Korean-Communication Function Classification System. Participation restriction was measured using the Korean-Frequency of Participation Questionnaire. Physical or occupational therapists and parents collected the data. [Results] All levels of the functional classification systems were significantly negatively correlated with Korean-Frequency of Participation Questionnaire ratings (r= −0.382 to −0.477). The Korean-Frequency of Participation Questionnaire ratings differed significantly with respect to the functional classification systems; in particular, the differences in the ratings of levels I and V were significant. The Korean-Communication Function Classification System and Korean-Gross Motor Function Classification System were significant predictors of participation, explaining 26.5% of the variance. [Conclusion] Intervention programs are required to promote communication skills and gross motor ability in order to improve the participation of children with cerebral palsy. PMID:26357445

  17. Are Dietary Restraint Scales Valid Measures of Moderate- to Long-Term Dietary Restriction? Objective Biological and Behavioral Data Suggest Not

    ERIC Educational Resources Information Center

    Stice, Eric; Cooper, Jamie A.; Schoeller, Dale A.; Tappe, Karyn; Lowe, Michael R.

    2007-01-01

    Prospective studies indicate that elevated scores on dietary restraint scales predict bulimic symptom onset, but experiments indicate that assignment to dietary restriction interventions reduces bulimic symptoms. One possible explanation for the inconsistent findings is that the dietary restraint scales used in the former studies are not valid…

  18. Sleep active cortical neurons expressing neuronal nitric oxide synthase are active after both acute sleep deprivation and chronic sleep restriction.

    PubMed

    Zielinski, M R; Kim, Y; Karpova, S A; Winston, S; McCarley, R W; Strecker, R E; Gerashchenko, D

    2013-09-01

    Non-rapid eye movement (NREM) sleep electroencephalographic (EEG) delta power (~0.5-4 Hz), also known as slow wave activity (SWA), is typically enhanced after acute sleep deprivation (SD) but not after chronic sleep restriction (CSR). Recently, sleep-active cortical neurons expressing neuronal nitric oxide synthase (nNOS) were identified and associated with enhanced SWA after short acute bouts of SD (i.e., 6h). However, the relationship between cortical nNOS neuronal activity and SWA during CSR is unknown. We compared the activity of cortical neurons expressing nNOS (via c-Fos and nNOS immuno-reactivity, respectively) and sleep in rats in three conditions: (1) after 18-h of acute SD; (2) after five consecutive days of sleep restriction (SR) (18-h SD per day with 6h ad libitum sleep opportunity per day); (3) and time-of-day matched ad libitum sleep controls. Cortical nNOS neuronal activity was enhanced during sleep after both 18-h SD and 5 days of SR treatments compared to control treatments. SWA and NREM sleep delta energy (the product of NREM sleep duration and SWA) were positively correlated with enhanced cortical nNOS neuronal activity after 18-h SD but not 5days of SR. That neurons expressing nNOS were active after longer amounts of acute SD (18h vs. 6h reported in the literature) and were correlated with SWA further suggest that these cells might regulate SWA. However, since these neurons were active after CSR when SWA was not enhanced, these findings suggest that mechanisms downstream of their activation are altered during CSR. PMID:23685166

  19. Rapid restriction enzyme free detection of DNA methyltransferase activity based on DNA-templated silver nanoclusters.

    PubMed

    Kermani, Hanie Ahmadzade; Hosseini, Morteza; Dadmehr, Mehdi; Ganjali, Mohammad Reza

    2016-06-01

    DNA methylation has significant roles in gene regulation. DNA methyltransferase (MTase) enzyme characterizes DNA methylation and also induces an aberrant methylation pattern that is related to many diseases, especially cancers. Thus, it is required to develop a method to detect the DNA MTase activity. In this study, we developed a new sensitive and reliable method for methyltransferase activity assay by employing DNA-templated silver nanoclusters (DNA/Ag NCs) without using restriction enzymes. The Ag NCs have been utilized for the determination of M.SssI MTase activity and its inhibition. We designed an oligonucleotide probe which contained an inserted six-cytosine loop as Ag NCs formation template. The changes in fluorescence intensity were monitored to quantify the M.SssI activity. The fluorescence spectra showed a linear decrease in the range of 0.4 to 20 U/ml with a detection limit of 0.1 U/ml, which was significant compared with previous reports. The proposed method was applied successfully for demonstrating the Gentamicin effect as MTase inhibitor. The proposed method showed convenient reproducibility and sensitivity indicating its potential for the determination of methyltransferase activity. PMID:27052776

  20. A restricted population of CB1 cannabinoid receptors with neuroprotective activity

    PubMed Central

    Chiarlone, Anna; Bellocchio, Luigi; Blázquez, Cristina; Resel, Eva; Soria-Gómez, Edgar; Cannich, Astrid; Ferrero, José J.; Sagredo, Onintza; Benito, Cristina; Romero, Julián; Sánchez-Prieto, José; Lutz, Beat; Fernández-Ruiz, Javier; Galve-Roperh, Ismael; Guzmán, Manuel

    2014-01-01

    The CB1 cannabinoid receptor, the main molecular target of endocannabinoids and cannabis active components, is the most abundant G protein-coupled receptor in the mammalian brain. Of note, CB1 receptors are expressed at the synapses of two opposing (i.e., GABAergic/inhibitory and glutamatergic/excitatory) neuronal populations, so the activation of one and/or another receptor population may conceivably evoke different effects. Despite the widely reported neuroprotective activity of the CB1 receptor in animal models, the precise pathophysiological relevance of those two CB1 receptor pools in neurodegenerative processes is unknown. Here, we first induced excitotoxic damage in the mouse brain by (i) administering quinolinic acid to conditional mutant animals lacking CB1 receptors selectively in GABAergic or glutamatergic neurons, and (ii) manipulating corticostriatal glutamatergic projections remotely with a designer receptor exclusively activated by designer drug pharmacogenetic approach. We next examined the alterations that occur in the R6/2 mouse, a well-established model of Huntington disease, upon (i) fully knocking out CB1 receptors, and (ii) deleting CB1 receptors selectively in corticostriatal glutamatergic or striatal GABAergic neurons. The data unequivocally identify the restricted population of CB1 receptors located on glutamatergic terminals as an indispensable player in the neuroprotective activity of (endo)cannabinoids, therefore suggesting that this precise receptor pool constitutes a promising target for neuroprotective therapeutic strategies. PMID:24843137

  1. A Krebs Cycle Component Limits Caspase Activation Rate through Mitochondrial Surface Restriction of CRL Activation.

    PubMed

    Aram, Lior; Braun, Tslil; Braverman, Carmel; Kaplan, Yosef; Ravid, Liat; Levin-Zaidman, Smadar; Arama, Eli

    2016-04-01

    How cells avoid excessive caspase activity and unwanted cell death during apoptotic caspase-mediated removal of large cellular structures is poorly understood. We investigate caspase-mediated extrusion of spermatid cytoplasmic contents in Drosophila during spermatid individualization. We show that a Krebs cycle component, the ATP-specific form of the succinyl-CoA synthetase β subunit (A-Sβ), binds to and activates the Cullin-3-based ubiquitin ligase (CRL3) complex required for caspase activation in spermatids. In vitro and in vivo evidence suggests that this interaction occurs on the mitochondrial surface, thereby limiting the source of CRL3 complex activation to the vicinity of this organelle and reducing the potential rate of caspase activation by at least 60%. Domain swapping between A-Sβ and the GTP-specific SCSβ (G-Sβ), which functions redundantly in the Krebs cycle, show that the metabolic and structural roles of A-Sβ in spermatids can be uncoupled, highlighting a moonlighting function of this Krebs cycle component in CRL activation. PMID:27052834

  2. Tissue Plasminogen Activator Expression Is Restricted to Subsets of Excitatory Pyramidal Glutamatergic Neurons.

    PubMed

    Louessard, Morgane; Lacroix, Alexandre; Martineau, Magalie; Mondielli, Gregoire; Montagne, Axel; Lesept, Flavie; Lambolez, Bertrand; Cauli, Bruno; Mothet, Jean-Pierre; Vivien, Denis; Maubert, Eric

    2016-09-01

    Although the extracellular serine protease tissue plasminogen activator (tPA) is involved in pathophysiological processes such as learning and memory, anxiety, epilepsy, stroke, and Alzheimer's disease, information about its regional, cellular, and subcellular distribution in vivo is lacking. In the present study, we observed, in healthy mice and rats, the presence of tPA in endothelial cells, oligodendrocytes, mastocytes, and ependymocytes, but not in pericytes, microglial cells, and astrocytes. Moreover, blockage of the axo-dendritic transport unmasked tPA expression in neurons of cortical and hippocampal areas. Interestingly, combined electrophysiological recordings, single-cell reverse transcription polymerase chain reaction (RT-PCR), and immunohistological analyses revealed that the presence of tPA is restricted to subsets of excitatory pyramidal glutamatergic neurons. We further evidenced that tPA is stored in synaptobrevin-2-positive glutamatergic synaptic vesicles. Based on all these data, we propose the existence of tPA-ergic neurons in the mature brain. PMID:26377106

  3. Restricted mobility of specific functional groups reduces anti-cancer drug activity in healthy cells

    DOE PAGESBeta

    Martins, Murillo L.; Ignazzi, Rosanna; Eckert, Juergen; Watts, Benjamin; Kaneno, Ramon; Zambuzzi, Willian F.; Daemen, Luke; Saeki, Margarida J.; Bordallo, Heloisa N.

    2016-03-02

    Here, the most common cancer treatments currently available are radio- and chemo-therapy. These therapies have, however, drawbacks, such as, the reduction in quality of life and the low efficiency of radiotherapy in cases of multiple metastases. To lessen these effects, we have encapsulated an anti-cancer drug into a biocompatible matrix. In-vitro assays indicate that this bio-nanocomposite is able to interact and cause morphological changes in cancer cells. Meanwhile, no alterations were observed in monocytes and fibroblasts, indicating that this system might carry the drug in living organisms with reduced clearance rate and toxicity. X-rays and neutrons were used to investigatemore » the carrier structure, as well as to assess the drug mobility within the bio-nanocomposite. In conclusion, from these unique data we show that partial mobility restriction of active groups of the drug molecule suggests why this carrier design is potentially safer to healthy cells.« less

  4. Restricted mobility of specific functional groups reduces anti-cancer drug activity in healthy cells

    PubMed Central

    Martins, Murillo L.; Ignazzi, Rosanna; Eckert, Juergen; Watts, Benjamin; Kaneno, Ramon; Zambuzzi, Willian F.; Daemen, Luke; Saeki, Margarida J.; Bordallo, Heloisa N.

    2016-01-01

    The most common cancer treatments currently available are radio- and chemo-therapy. These therapies have, however, drawbacks, such as, the reduction in quality of life and the low efficiency of radiotherapy in cases of multiple metastases. To lessen these effects, we have encapsulated an anti-cancer drug into a biocompatible matrix. In-vitro assays indicate that this bio-nanocomposite is able to interact and cause morphological changes in cancer cells. Meanwhile, no alterations were observed in monocytes and fibroblasts, indicating that this system might carry the drug in living organisms with reduced clearance rate and toxicity. X-rays and neutrons were used to investigate the carrier structure, as well as to assess the drug mobility within the bio-nanocomposite. From these unique data we show that partial mobility restriction of active groups of the drug molecule suggests why this carrier design is potentially safer to healthy cells. PMID:26932808

  5. Restricted mobility of specific functional groups reduces anti-cancer drug activity in healthy cells

    NASA Astrophysics Data System (ADS)

    Martins, Murillo L.; Ignazzi, Rosanna; Eckert, Juergen; Watts, Benjamin; Kaneno, Ramon; Zambuzzi, Willian F.; Daemen, Luke; Saeki, Margarida J.; Bordallo, Heloisa N.

    2016-03-01

    The most common cancer treatments currently available are radio- and chemo-therapy. These therapies have, however, drawbacks, such as, the reduction in quality of life and the low efficiency of radiotherapy in cases of multiple metastases. To lessen these effects, we have encapsulated an anti-cancer drug into a biocompatible matrix. In-vitro assays indicate that this bio-nanocomposite is able to interact and cause morphological changes in cancer cells. Meanwhile, no alterations were observed in monocytes and fibroblasts, indicating that this system might carry the drug in living organisms with reduced clearance rate and toxicity. X-rays and neutrons were used to investigate the carrier structure, as well as to assess the drug mobility within the bio-nanocomposite. From these unique data we show that partial mobility restriction of active groups of the drug molecule suggests why this carrier design is potentially safer to healthy cells.

  6. Restricted mobility of specific functional groups reduces anti-cancer drug activity in healthy cells.

    PubMed

    Martins, Murillo L; Ignazzi, Rosanna; Eckert, Juergen; Watts, Benjamin; Kaneno, Ramon; Zambuzzi, Willian F; Daemen, Luke; Saeki, Margarida J; Bordallo, Heloisa N

    2016-01-01

    The most common cancer treatments currently available are radio- and chemo-therapy. These therapies have, however, drawbacks, such as, the reduction in quality of life and the low efficiency of radiotherapy in cases of multiple metastases. To lessen these effects, we have encapsulated an anti-cancer drug into a biocompatible matrix. In-vitro assays indicate that this bio-nanocomposite is able to interact and cause morphological changes in cancer cells. Meanwhile, no alterations were observed in monocytes and fibroblasts, indicating that this system might carry the drug in living organisms with reduced clearance rate and toxicity. X-rays and neutrons were used to investigate the carrier structure, as well as to assess the drug mobility within the bio-nanocomposite. From these unique data we show that partial mobility restriction of active groups of the drug molecule suggests why this carrier design is potentially safer to healthy cells. PMID:26932808

  7. Amplicon restriction patterns associated with nitrogenase activity of root nodules for selection of superior Myrica seedlings.

    PubMed

    Yanthan, Mhathung; Misra, Arvind K

    2013-11-01

    Trees of Myrica sp. grow abundantly in the forests of Meghalaya, India. These trees are actinorhizal and harbour nitrogen-fixing Frankia in their root nodules and contribute positively towards the enhancement of nitrogen status of forest areas. They can be used in rejuvenation of mine spoils and nitrogen-depleted fallow lands generated due to slash and burn agriculture practiced in the area. We have studied the association of amplicon restriction patterns (ARPs) of Myrica ribosomal RNA gene and internal transcribed spacer (ITS) region and nitrogenase activity of its root nodules. We found that ARPs thus obtained could be used as markers for early screening of seedlings that could support strains of Frankia that fix atmospheric nitrogen more efficiently. PMID:24287658

  8. Influence of age and caloric restriction on liver glycolytic enzyme activities and metabolite concentrations in mice.

    PubMed

    Hagopian, Kevork; Ramsey, Jon J; Weindruch, Richard

    2003-03-01

    The influence of caloric restriction (CR) from 2 months of age on the activities of liver glycolytic enzymes and metabolite levels was studied in young and old mice. Livers were sampled 48 h after the last scheduled feeding time. Old mice on CR showed significant decreases in the activities of all the enzymes studied, except for aldolase, triosephosphate isomerase and phosphoglycerate mutase, which were unchanged. The metabolites glucose, glucose-6-phosphate, fructose-6-phosphate, pyruvate and lactate were lower while fructose-1,6-bisphosphate, glyceraldehyde-3-phosphate, dihydroxyacetone phosphate, 3-phosphoglycerate and phosphoenolpyruvate were increased in old CR. Young mice on CR also showed reduced enzyme activities, except for aldolase, triosephosphate isomerase and enolase which were unchanged when compared with young controls. The metabolites glucose, glucose-6-phosphate, fructose-6-phosphate and pyruvate were decreased when compared with young controls, while phosphoenolpyruvate was increased. Ketone bodies increased (65%) in old, but not young, CR mice while fructose-2,6-bisphosphate decreased in both young (22%) and old CR (28%) mice. The results indicate that decreased hepatic glucose levels in CR mice are associated with decreased enzyme activities but not a uniform decrease in metabolite levels. Increased ketone body levels indicate increased utilization of non-carbohydrate fuels while decreased fructose-2,6-bisphosphate level suggests its importance in the control of glycolysis in CR. PMID:12581789

  9. Synthesis and antioxidant activity of polyhydroxylated trans-restricted 2-arylcinnamic acids.

    PubMed

    Miliovsky, Mitko; Svinyarov, Ivan; Prokopova, Elena; Batovska, Daniela; Stoyanov, Simeon; Bogdanov, Milen G

    2015-01-01

    A series of sixteen polyhydroxylated trans-restricted 2-arylcinnamic acid analogues 3a-p were synthesized through a one-pot reaction between homophthalic anhydrides and various aromatic aldehydes, followed by treatment with BBr3. The structure of the newly synthesized compounds was confirmed by spectroscopic methods and the configuration around the double bond was unequivocally estimated by means of gated decoupling 13C-NMR spectra. It was shown that the trans-cinnamic acid fragment incorporated into the target compounds' structure ensures the cis-configuration of the stilbene backbone and prevents further isomerization along the carbon-carbon double bond. The antioxidant activity of compounds 3a-p was measured against 1,1-diphenyl-2-picrylhydrazyl (DPPH●), hydroxyl (OH●) and superoxide (O2●▬) radicals. The results obtained showed that the tested compounds possess higher activities than natural antioxidants such as protocatechuic acid, caffeic acid and gallic acid. Moreover, it was shown that a combination of two different and independently acting fragments of well-known pharmacological profiles into one covalently bonded hybrid molecule evoke a synergistic effect resulting in higher than expected activity. To rationalize the apparent antioxidant activity and to establish the mechanism of action, a SAR analysis and DFT quantum chemical computations were also performed. PMID:25648597

  10. Kremen1 restricts Dkk activity during posterior lateral line development in zebrafish

    PubMed Central

    McGraw, Hillary F.; Culbertson, Maya D.; Nechiporuk, Alex V.

    2014-01-01

    Canonical Wnt signaling plays crucial roles during development and disease. How Wnt signaling is modulated in different in vivo contexts is currently not well understood. Here, we investigate the modulation of Wnt signaling in the posterior lateral line primordium (pLLP), a cohort of ∼100 cells that collectively migrate along the trunk of the zebrafish embryo. The pLLP comprises proliferative progenitor cells and organized epithelial cells that will form the mechanosensory organs of the posterior lateral line. Wnt signaling is active in the leading progenitor zone of the pLLP and restricted from the trailing zone through expression of the secreted Wnt inhibitors dkk1b and dkk2. We have identified a zebrafish strain, krm1nl10, which carries a mutation in the kremen1 gene, a non-obligate co-receptor for the Dkk family of proteins. Previous studies have shown that Kremen1 inhibits Wnt signaling by facilitating internalization of the Kremen1-Dkk-Lrp5/6 complex. Surprisingly, we found that disruption of Kremen1 in the pLLP exhibited molecular and cellular phenotypes associated with a decrease rather than overactivation of Wnt signaling. Transplantation of wild-type cells into the mutant primordia failed to rescue the krm1nl10 phenotype, thus revealing that the effects of Kremen1 loss are non-cell-autonomous. Finally, ectopic expression of Dkk1b-mTangerine protein revealed larger spread of the fusion protein in the mutant primordia compared with the wild type. Based on our data, we propose a novel mechanism in which Kremen1 modulates Wnt activity by restricting the range of secreted Dkk proteins during collective cell migration in the pLLP. PMID:25038040

  11. Kremen1 restricts Dkk activity during posterior lateral line development in zebrafish.

    PubMed

    McGraw, Hillary F; Culbertson, Maya D; Nechiporuk, Alex V

    2014-08-01

    Canonical Wnt signaling plays crucial roles during development and disease. How Wnt signaling is modulated in different in vivo contexts is currently not well understood. Here, we investigate the modulation of Wnt signaling in the posterior lateral line primordium (pLLP), a cohort of ~100 cells that collectively migrate along the trunk of the zebrafish embryo. The pLLP comprises proliferative progenitor cells and organized epithelial cells that will form the mechanosensory organs of the posterior lateral line. Wnt signaling is active in the leading progenitor zone of the pLLP and restricted from the trailing zone through expression of the secreted Wnt inhibitors dkk1b and dkk2. We have identified a zebrafish strain, krm1(nl10), which carries a mutation in the kremen1 gene, a non-obligate co-receptor for the Dkk family of proteins. Previous studies have shown that Kremen1 inhibits Wnt signaling by facilitating internalization of the Kremen1-Dkk-Lrp5/6 complex. Surprisingly, we found that disruption of Kremen1 in the pLLP exhibited molecular and cellular phenotypes associated with a decrease rather than overactivation of Wnt signaling. Transplantation of wild-type cells into the mutant primordia failed to rescue the krm1(nl10) phenotype, thus revealing that the effects of Kremen1 loss are non-cell-autonomous. Finally, ectopic expression of Dkk1b-mTangerine protein revealed larger spread of the fusion protein in the mutant primordia compared with the wild type. Based on our data, we propose a novel mechanism in which Kremen1 modulates Wnt activity by restricting the range of secreted Dkk proteins during collective cell migration in the pLLP. PMID:25038040

  12. Activation of individual L1 retrotransposon instances is restricted to cell-type dependent permissive loci

    PubMed Central

    Philippe, Claude; Vargas-Landin, Dulce B; Doucet, Aurélien J; van Essen, Dominic; Vera-Otarola, Jorge; Kuciak, Monika; Corbin, Antoine; Nigumann, Pilvi; Cristofari, Gaël

    2016-01-01

    LINE-1 (L1) retrotransposons represent approximately one sixth of the human genome, but only the human-specific L1HS-Ta subfamily acts as an endogenous mutagen in modern humans, reshaping both somatic and germline genomes. Due to their high levels of sequence identity and the existence of many polymorphic insertions absent from the reference genome, the transcriptional activation of individual genomic L1HS-Ta copies remains poorly understood. Here we comprehensively mapped fixed and polymorphic L1HS-Ta copies in 12 commonly-used somatic cell lines, and identified transcriptional and epigenetic signatures allowing the unambiguous identification of active L1HS-Ta copies in their genomic context. Strikingly, only a very restricted subset of L1HS-Ta loci - some being polymorphic among individuals - significantly contributes to the bulk of L1 expression, and these loci are differentially regulated among distinct cell lines. Thus, our data support a local model of L1 transcriptional activation in somatic cells, governed by individual-, locus-, and cell-type-specific determinants. DOI: http://dx.doi.org/10.7554/eLife.13926.001 PMID:27016617

  13. Setdb1 maintains hematopoietic stem and progenitor cells by restricting the ectopic activation of nonhematopoietic genes.

    PubMed

    Koide, Shuhei; Oshima, Motohiko; Takubo, Keiyo; Yamazaki, Satoshi; Nitta, Eriko; Saraya, Atsunori; Aoyama, Kazumasa; Kato, Yuko; Miyagi, Satoru; Nakajima-Takagi, Yaeko; Chiba, Tetsuhiro; Matsui, Hirotaka; Arai, Fumio; Suzuki, Yutaka; Kimura, Hiroshi; Nakauchi, Hiromitsu; Suda, Toshio; Shinkai, Yoichi; Iwama, Atsushi

    2016-08-01

    Setdb1, also known as Eset, is a methyltransferase that catalyzes trimethylation of H3K9 (H3K9me3) and plays an essential role in the silencing of endogenous retroviral elements (ERVs) in the developing embryo and embryonic stem cells (ESCs). Its role in somatic stem cells, however, remains unclear because of the early death of Setdb1-deficient embryos. We demonstrate here that Setdb1 is the first H3K9 methyltransferase shown to be essential for the maintenance of hematopoietic stem and progenitor cells (HSPCs) in mice. The deletion of Setdb1 caused the rapid depletion of hematopoietic stem and progenitor cells (HSPCs), as well as leukemic stem cells. In contrast to ESCs, ERVs were largely repressed in Setdb1-deficient HSPCs. A list of nonhematopoietic genes was instead ectopically activated in HSPCs after reductions in H3K9me3 levels, including key gluconeogenic enzyme genes fructose-1,6-bisphosphatase 1 (Fbp1) and Fbp2 The ectopic activation of gluconeogenic enzymes antagonized glycolysis and impaired ATP production, resulting in a compromised repopulating capacity of HSPCs. Our results demonstrate that Setdb1 maintains HSPCs by restricting the ectopic activation of nonhematopoietic genes detrimental to their function and uncover that the gluconeogenic pathway is one of the critical targets of Setdb1 in HSPCs. PMID:27301860

  14. Effect of restricted motion in high temperature on enzymatic activity of the pancreas

    NASA Technical Reports Server (NTRS)

    Abdusattarov, A.; Smirnova, G. I.

    1980-01-01

    Effects of 30 day hypodynamia coupled with high temperature (35-36 C) on enzymatic activity of the pancreas of male adult rats were studied. The test animals were divided into four groups. Group one served as controls (freedom of movement and a temperature of 25-26 C, considered optimal). The remaining animals were divided into three additional groups: Group two freedom of movement but high temperature (35-36 C); group three hypodynamia but an optimal temperature; group four hypodynamia and 35-36 C. Considerable change in the enzymatic activity in the pancreas of the four groups is observed in three experimental groups (two, three, and four) as compared to the control (group one). The results indicate that adaption of the organism to the thermal factor and restricted movement is accompanied by a change in the enzymatic spectrum of the pancreas. With the combined effect of these two stresses under conditions of the adaption of the organism especially sharp shifts occur in the enzymatic activity.

  15. Restricting activation-induced cytidine deaminase tumorigenic activity in B lymphocytes.

    PubMed

    Casellas, Rafael; Yamane, Arito; Kovalchuk, Alexander L; Potter, Michael

    2009-03-01

    DNA breaks play an essential role in germinal centre B cells as intermediates to immunoglobulin class switching, a recombination process initiated by activation-induced cytidine deaminase (AID). Immunoglobulin gene hypermutation is likewise catalysed by AID but is believed to occur via single-strand DNA breaks. When improperly repaired, AID-mediated lesions can promote chromosomal translocations (CTs) that juxtapose the immunoglobulin loci to heterologous genomic sites, including oncogenes. Two of the most studied translocations are the t(8;14) and T(12;15), which deregulate cMyc in human Burkitt's lymphomas and mouse plasmacytomas, respectively. While a complete understanding of the aetiology of such translocations is lacking, recent studies using diverse mouse models have shed light on two important issues: (1) the extent to which non-specific or AID-mediated DNA lesions promote CTs, and (2) the safeguard mechanisms that B cells employ to prevent AID tumorigenic activity. Here we review these advances and discuss the usage of pristane-induced mouse plasmacytomas as a tool to investigate the origin of Igh-cMyc translocations and B-cell tumorigenesis. PMID:19302140

  16. Dietary salt restriction activates mineralocorticoid receptor signaling in volume-overloaded heart failure.

    PubMed

    Mori, Tatsuhiko; Kurumazuka, Daisuke; Matsumoto, Chika; Shirakawa, Hisashi; Kimura, Sayaka; Kitada, Kento; Kobayashi, Kana; Matsuda, Hirohisa; Hayashi, Tetsuya; Kitaura, Yasushi; Matsumura, Yasuo

    2009-11-25

    Whether a high plasma aldosterone concentration induced by strict salt restriction promotes cardiac remodeling remains controversial. Male Sprague-Dawley rats at 10weeks of age were given normal salt (NS) (1.5% NaCl) or low salt (LS) (0.05% NaCl) diets. Each animal underwent aortocaval fistula creation for volume-overloaded heart failure or sham surgery. All rats with a fistula received either vehicle or a non-hypotensive dose of spironolactone (200mg/kg/day) by gavage. Two weeks later, the LS diet significantly increased the plasma aldosterone level in the sham-operated and fistula-created rats (2677+/-662pg/ml and 2406+/-422pg/ml) compared with that in rats given the NS diet (518+/-18pg/ml and 362+/-45pg/ml, respectively). In sham-operated rats, the difference in plasma aldosterone level did not affect the extent of myocardial fibrosis (1.8+/-0.1% with LS diet vs. 1.5+/-0.3% with NS diet). However, the increase in myocardial fibrosis in fistula-created rats was more prominent with the LS diet than with the NS diet (4.7+/-0.3% vs. 3.4+/-0.1%). In addition, the fistula-created rats on the LS diet expressed significantly increased oxidative stress and transforming growth factor-beta compared with those on the NS diets (P<0.05). These increases in the fistula-created rats on the LS diet were significantly suppressed by the non-hypotensive dose of spironolactone (P<0.05). These results suggest that increased plasma aldosterone level with strict salt restriction activated the mineralocorticoid receptor signaling in volume-overloaded condition, resulting in increased myocardial fibrosis. PMID:19766104

  17. AMP Activated Protein Kinase Is Indispensable for Myocardial Adaptation to Caloric Restriction in Mice

    PubMed Central

    Chen, Kai; Kobayashi, Satoru; Xu, Xianmin; Viollet, Benoit; Liang, Qiangrong

    2013-01-01

    Caloric restriction (CR) is a robust dietary intervention known to enhance cardiovascular health. AMP activated protein kinase (AMPK) has been suggested to mediate the cardioprotective effects of CR. However, this hypothesis remains to be tested by using definitive loss-of-function animal models. In the present study, we subjected AMPKα2 knockout (KO) mice and their wild type (WT) littermates to a CR regimen that reduces caloric intake by 20%–40% for 4 weeks. CR decreased body weight, heart weight and serum levels of insulin in both WT and KO mice to the same degree, indicating the effectiveness of the CR protocol. CR activated cardiac AMPK signaling in WT mice, but not in AMPKα2 KO mice. Correspondingly, AMPKα2 KO mice had markedly reduced cardiac function during CR as determined by echocardiography and hemodynamic measurements. The compromised cardiac function was associated with increased markers of oxidative stress, endoplasmic reticulum stress and myocyte apoptosis. Mechanistically, CR down-regulated the expression of ATP5g2, a subunit of mitochondrial ATP synthase, and reduced ATP content in AMPKα2 KO hearts, but not in WT hearts. In addition, CR accelerated cardiac autophagic flux in WT mice, but failed to do so in AMPKα2 KO mice. These results demonstrated that without AMPK, CR triggers adverse effects that can lead to cardiac dysfunction, suggesting that AMPK signaling pathway is indispensible for energy homeostasis and myocardial adaptation to CR, a dietary intervention that normally produces beneficial cardiac effects. PMID:23527250

  18. Tracking the activity-dependent diffusion of synaptic proteins using restricted photoconversion of Dendra2

    PubMed Central

    Cassé, Frédéric; Martin, Stéphane

    2015-01-01

    Spines are small protrusions on dendritic membranes receiving inputs from axonal termini. They consist in a head connected to the dendritic shaft by a narrow neck and contain multiple synaptic proteins that interact in a coordinated manner to allow for synaptic communication. This process involves many proteins that are moving in and out spines. However, comparing this synaptodendritic movement in basal and stimulated conditions is very challenging. Here we describe an elegant method to measure the activity-dependent diffusion of synaptic proteins using Dendra2 photoconversion. We provide a successful method to obtain Dendra2-photoconverted images and a step-by-step procedure to analyze the data. This live-imaging approach may also apply to investigate the diffusion of proteins across other subcellular compartments or organelles including but not restricted to, nucleus, nucleolus, ER, or vesicular structures. Once the imaging system is set up, data can be acquired in 1–30 min and analyzed in approximately 1–4 h. PMID:26441538

  19. Activation of Nod1 Signaling Induces Fetal Growth Restriction and Death through Fetal and Maternal Vasculopathy

    PubMed Central

    Nishio, Hisanori; Takada, Hidetoshi; Sakai, Yasunari; Nanishi, Etsuro; Ochiai, Masayuki; Onimaru, Mitsuho; Chen, Si Jing; Matsui, Toshiro; Hara, Toshiro

    2016-01-01

    Intrauterine fetal growth restriction (IUGR) and death (IUFD) are both serious problems in the perinatal medicine. Fetal vasculopathy is currently considered to account for a pathogenic mechanism of IUGR and IUFD. We previously demonstrated that an innate immune receptor, the nucleotide-binding oligomerization domain-1 (Nod1), contributed to the development of vascular inflammations in mice at postnatal stages. However, little is known about the deleterious effects of activated Nod1 signaling on embryonic growth and development. We report that administration of FK565, one of the Nod1 ligands, to pregnant C57BL/6 mice induced IUGR and IUFD. Mass spectrometry analysis revealed that maternally injected FK565 was distributed to the fetal tissues across placenta. In addition, maternal injection of FK565 induced robust increases in the amounts of CCL2, IL-6, and TNF proteins as well as NO in maternal, placental and fetal tissues. Nod1 was highly expressed in fetal vascular tissues, where significantly higher levels of CCL2 and IL-6 mRNAs were induced with maternal injection of FK565 than those in other tissues. Using Nod1-knockout mice, we verified that both maternal and fetal tissues were involved in the development of IUGR and IUFD. Furthermore, FK565 induced upregulation of genes associated with immune response, inflammation, and apoptosis in fetal vascular tissues. Our data thus provided new evidence for the pathogenic role of Nod1 in the development of IUGR and IUFD at the maternal-fetal interface. PMID:26880761

  20. Muscle ultrastructural changes from exhaustive exercise performed after prolonged restricted activity and retraining in dogs

    NASA Technical Reports Server (NTRS)

    Nazar, K.; Greenleaf, J. E.; Philpott, D.; Pohoska, E.; Olszewska, K.; Kaciuba-Uscilko, H.

    1991-01-01

    The effect of exhaustive treadmill exercise on ultrastructural changes in the quadriceps femoris muscle was studied in 7 normal, healthy dogs, before and after restricted activity (RA), and following a subsequent 2 month treadmill exercise retraining period for the 5 mo group. Mean time to exhaustion in the 2 mo group decreased from 177 + or - 22 min before to 90 + or - 32 min after RA. Retraining increased tolerance to 219 + or - 73 min; 24 pct. above the before RA and 143 pct. above the after RA time. After RA exhaustion time in the 5 mo group was 25 and 45 min. Before RA, pre-exercise muscle structure was normal and post exercise there was only slight swelling of mitochondria. After RA, pre-exercise, numerous glycogen granules and lipid droplets appeared in the muscle fibers, mitochondria were smaller, and sarcoplasmic reticulum channels widened; post exercise these changes were accentuated and some areas were devoid of glycogen, and there was fiber degradation. After 5 mo RA pre-exercise there were more pronounced changes; mitochondria were very small and dense, there were many lipid droplets, myofibrils were often separated, and the fibers appeared edematous and degenerating; post exercise the sarcoplasmic reticulum was swollen, no glycogen was present, and there was marked swelling and deformation of mitochondria. After retraining, both pre-exercise and post exercise there was still evidence of fiber degeneration. Thus, susceptibility of active skeletal muscle structures and subcellular elements, e.g., mitochondria, to the action of damaging factors occurring during exhaustive exercise is enhanced considerably by prolonged disuse.

  1. An overview of the issues: physiological effects of bed rest and restricted physical activity

    NASA Technical Reports Server (NTRS)

    Convertino, V. A.; Bloomfield, S. A.; Greenleaf, J. E.

    1997-01-01

    Reduction of exercise capacity with confinement to bed rest is well recognized. Underlying physiological mechanisms include dramatic reductions in maximal stroke volume, cardiac output, and oxygen uptake. However, bed rest by itself does not appear to contribute to cardiac dysfunction. Increased muscle fatigue is associated with reduced muscle blood flow, red cell volume, capillarization and oxidative enzymes. Loss of muscle mass and bone density may be reflected by reduced muscle strength and higher risk for injury to bones and joints. The resultant deconditioning caused by bed rest can be independent of the primary disease and physically debilitating in patients who attempt to reambulate to normal active living and working. A challenge to clinicians and health care specialists has been the identification of appropriate and effective methods to restore physical capacity of patients during or after restricted physical activity associated with prolonged bed rest. The examination of physiological responses to bed rest deconditioning and exercise training in healthy subjects has provided significant information to develop effective rehabilitation treatments. The successful application of acute exercise to enhance orthostatic stability, daily endurance exercise to maintain aerobic capacity, or specific resistance exercises to maintain musculoskeletal integrity rather than the use of surgical, pharmacological, and other medical treatments for clinical conditions has been enhanced by investigation and understanding of underlying mechanisms that distinguish physical deconditioning from the disease. This symposium presents an overview of cardiovascular and musculoskeletal deconditioning associated with reduced physical work capacity following prolonged bed rest and exercise training regimens that have proven successful in ameliorating or reversing these adverse effects.

  2. Restricted feeding-induced sleep, activity, and body temperature changes in normal and preproghrelin-deficient mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Behavioral and physiological rhythms can be entrained by daily restricted feeding (RF), indicating the existence of a food-entrainable oscillator (FEO). One manifestation of the presence of FEO is anticipatory activity to regularly scheduled feeding. In the present study, we tested if intact ghrelin...

  3. Scaling and Criticality in Large-Scale Neuronal Activity

    NASA Astrophysics Data System (ADS)

    Linkenkaer-Hansen, K.

    The human brain during wakeful rest spontaneously generates large-scale neuronal network oscillations at around 10 and 20 Hz that can be measured non-invasively using magnetoencephalography (MEG) or electroencephalography (EEG). In this chapter, spontaneous oscillations are viewed as the outcome of a self-organizing stochastic process. The aim is to introduce the general prerequisites for stochastic systems to evolve to the critical state and to explain their neurophysiological equivalents. I review the recent evidence that the theory of self-organized criticality (SOC) may provide a unifying explanation for the large variability in amplitude, duration, and recurrence of spontaneous network oscillations, as well as the high susceptibility to perturbations and the long-range power-law temporal correlations in their amplitude envelope.

  4. Partial Sleep Restriction Activates Immune Response-Related Gene Expression Pathways: Experimental and Epidemiological Studies in Humans

    PubMed Central

    Rantanen, Ville; Kronholm, Erkki; Surakka, Ida; van Leeuwen, Wessel M. A.; Lehto, Maili; Matikainen, Sampsa; Ripatti, Samuli; Härmä, Mikko; Sallinen, Mikael; Salomaa, Veikko; Jauhiainen, Matti; Alenius, Harri; Paunio, Tiina; Porkka-Heiskanen, Tarja

    2013-01-01

    Epidemiological studies have shown that short or insufficient sleep is associated with increased risk for metabolic diseases and mortality. To elucidate mechanisms behind this connection, we aimed to identify genes and pathways affected by experimentally induced, partial sleep restriction and to verify their connection to insufficient sleep at population level. The experimental design simulated sleep restriction during a working week: sleep of healthy men (N = 9) was restricted to 4 h/night for five nights. The control subjects (N = 4) spent 8 h/night in bed. Leukocyte RNA expression was analyzed at baseline, after sleep restriction, and after recovery using whole genome microarrays complemented with pathway and transcription factor analysis. Expression levels of the ten most up-regulated and ten most down-regulated transcripts were correlated with subjective assessment of insufficient sleep in a population cohort (N = 472). Experimental sleep restriction altered the expression of 117 genes. Eight of the 25 most up-regulated transcripts were related to immune function. Accordingly, fifteen of the 25 most up-regulated Gene Ontology pathways were also related to immune function, including those for B cell activation, interleukin 8 production, and NF-κB signaling (P<0.005). Of the ten most up-regulated genes, expression of STX16 correlated negatively with self-reported insufficient sleep in a population sample, while three other genes showed tendency for positive correlation. Of the ten most down-regulated genes, TBX21 and LGR6 correlated negatively and TGFBR3 positively with insufficient sleep. Partial sleep restriction affects the regulation of signaling pathways related to the immune system. Some of these changes appear to be long-lasting and may at least partly explain how prolonged sleep restriction can contribute to inflammation-associated pathological states, such as cardiometabolic diseases. PMID:24194869

  5. Effect of hyperhydration on bone mineralization in physically healthy subjects after prolonged restriction of motor activity

    NASA Astrophysics Data System (ADS)

    Zorbas, Yan G.; Federenko, Youri F.; Naexu, Konstantin A.

    The objective of this investigation was to evaluate the effect of a daily intake of fluid and salt supplementation (FSS) on bone mineralization in physically healthy male volunteers after exposure to hypokinesia (decreased number of steps taken/day) over a period of 364 days. The studies were performed after exposure to 364 days of hypokinesia (HK) on 18 physically healthy male volunteers who had an average VO2max of 65 ml/kg/min and were aged between 19 and 24 years. For the simulation of the hypokinetic effect the volunteers were kept under an average of 1000 steps/day. The subjects were divided into three equal groups of 6: 6 underwent a normal ambulatory life (control group), 6 were placed under HK (hypokinetic group) and the remaining 6 were subjected to HK and consumed a daily FSS (water 26 ml/kg body wt and NaCl 0.10 mg/kg body wt) (hyperhydrated group). The density of the ulnar, radius, tibia, fibular, lumbar vertebrae and calcenous was measured. Calcium and phosphorus changes, plasma volume, blood pressure and body weight were determined. Calcium content in the examined skeletal bones decreased more in the hypokinetic subjects than in the hyperhydrated subjects. Urinary calcium and phosphorus losses were more pronounced in hypokinetic than hyperhydrated subjects. Plasma volume and body weight increased in hyperhydrated subjects, while it decreased in hypokinetic subjects. It was concluded that a daily intake of FSS may be used to neutralize bone demineralization in physically healthy subjects during prolonged restriction of motor activity.

  6. Caloric restriction stimulates autophagy in rat cortical neurons through neuropeptide Y and ghrelin receptors activation.

    PubMed

    Ferreira-Marques, Marisa; Aveleira, Célia A; Carmo-Silva, Sara; Botelho, Mariana; Pereira de Almeida, Luís; Cavadas, Cláudia

    2016-07-01

    Caloric restriction is an anti-aging intervention known to extend lifespan in several experimental models, at least in part, by stimulating autophagy. Caloric restriction increases neuropeptide Y (NPY) in the hypothalamus and plasma ghrelin, a peripheral gut hormone that acts in hypothalamus to modulate energy homeostasis. NPY and ghrelin have been shown to be neuroprotective in different brain areas and to induce several physiological modifications similar to those induced by caloric restriction. However, the effect of NPY and ghrelin in autophagy in cortical neurons is currently not known. Using a cell culture of rat cortical neurons we investigate the involvement of NPY and ghrelin in caloric restriction-induced autophagy. We observed that a caloric restriction mimetic cell culture medium stimulates autophagy in rat cortical neurons and NPY or ghrelin receptor antagonists blocked this effect. On the other hand, exogenous NPY or ghrelin stimulate autophagy in rat cortical neurons. Moreover, NPY mediates the stimulatory effect of ghrelin on autophagy in rat cortical neurons. Since autophagy impairment occurs in aging and age-related neurodegenerative diseases, NPY and ghrelin synergistic effect on autophagy stimulation may suggest a new strategy to delay aging process. PMID:27441412

  7. Caloric restriction stimulates autophagy in rat cortical neurons through neuropeptide Y and ghrelin receptors activation

    PubMed Central

    Carmo-Silva, Sara; Botelho, Mariana; de Almeida, Luís Pereira; Cavadas, Cláudia

    2016-01-01

    Caloric restriction is an anti-aging intervention known to extend lifespan in several experimental models, at least in part, by stimulating autophagy. Caloric restriction increases neuropeptide Y (NPY) in the hypothalamus and plasma ghrelin, a peripheral gut hormone that acts in hypothalamus to modulate energy homeostasis. NPY and ghrelin have been shown to be neuroprotective in different brain areas and to induce several physiological modifications similar to those induced by caloric restriction. However, the effect of NPY and ghrelin in autophagy in cortical neurons is currently not known. Using a cell culture of rat cortical neurons we investigate the involvement of NPY and ghrelin in caloric restriction-induced autophagy. We observed that a caloric restriction mimetic cell culture medium stimulates autophagy in rat cortical neurons and NPY or ghrelin receptor antagonists blocked this effect. On the other hand, exogenous NPY or ghrelin stimulate autophagy in rat cortical neurons. Moreover, NPY mediates the stimulatory effect of ghrelin on autophagy in rat cortical neurons. Since autophagy impairment occurs in aging and age-related neurodegenerative diseases, NPY and ghrelin synergistic effect on autophagy stimulation may suggest a new strategy to delay aging process. PMID:27441412

  8. Reliability and Validity of the Physical Education Activities Scale

    ERIC Educational Resources Information Center

    Thomason, Diane L.; Feng, Du

    2016-01-01

    Background: Measuring adolescent perceptions of physical education (PE) activities is necessary in understanding determinants of school PE activity participation. This study assessed reliability and validity of the Physical Education Activities Scale (PEAS), a 41-item visual analog scale measuring high school adolescent perceptions of school PE…

  9. Does prey capture induce area-restricted search? A fine-scale study using GPS in a marine predator, the wandering albatross.

    PubMed

    Weimerskirch, Henri; Pinaud, David; Pawlowski, Frédéric; Bost, Charles-André

    2007-11-01

    In a patchy environment, predators are expected to increase turning rate and start an area-restricted search (ARS) when prey have been encountered, but few empirical data exist for large predators. By using GPS loggers with devices measuring prey capture, we studied how a marine predator adjusts foraging movements at various scales in relation to prey capture. Wandering albatrosses use two tactics, sit and wait and foraging in flight, the former tactic being three times less efficient than the latter. During flight foraging, birds caught large isolated prey and used ARS at scales varying from 5 to 90 km, with large-scale ARS being used only by young animals. Birds did not show strong responses to prey capture at a large scale, few ARS events occurred after prey capture, and birds did not have high rates of prey capture in ARS. Only at small scales did birds increase sinuosity after prey captures for a limited time period, and this occurred only after they had caught a large prey item within an ARS zone. When this species searches over a large scale, the most effective search rule was to follow a nearly straight path. ARS may be used to restrict search to a particular environment where prey capture is more predictable and profitable. PMID:17926295

  10. Scale-free brain activity: past, present and future

    PubMed Central

    He, Biyu J.

    2014-01-01

    Brain activity observed at many spatiotemporal scales exhibits a 1/f-like power spectrum, including neuronal membrane potentials, neural field potentials, noninvasive electroencephalography, magnetoencephalography and functional magnetic resonance imaging signals. A 1/f-like power spectrum is indicative of arrhythmic brain activity that does not contain a predominant temporal scale (hence, “scale-free”). This characteristic of scale-free brain activity distinguishes it from brain oscillations. While scale-free brain activity and brain oscillations coexist, our understanding of the former remains very limited. Recent research has shed light on the spatiotemporal organization, functional significance and potential generative mechanisms of scale-free brain activity, as well as its developmental and clinical relevance. A deeper understanding of this prevalent brain signal should provide new insights and analytical tools for cognitive neuroscience. PMID:24788139

  11. Ovine maternal nutrient restriction from mid to late gestation decreases heptic progesterone inactivating enzyme activity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Previously we have shown increased concentrations of progesterone and decreased liver weight in mid to late pregnant ewes provided a nutrient restricted vs. adequate diet. This alteration in peripheral progesterone could be due to increased synthesis and/or decreased clearance of progesterone. There...

  12. Caloric restriction.

    PubMed

    Speakman, John R; Mitchell, Sharon E

    2011-06-01

    Restricting the intake of calories has been practiced as a method for increasing both the length and quality of life for over 500 years. Experimental work confirming the success of this approach in animals has accumulated over the last 100 years. Lifelong caloric restriction (CR) may extend life by up to 50% in rodents, with progressively less impact the later in life it is started. This effect is matched by profound impacts on age related diseases including reduced risk of cancer, neurodegenerative disorders, autoimmune disease, cardiovascular disease and type II diabetes mellitus. The disposable soma theory of ageing suggests that CR evolved as a somatic protection response to enable animals to survive periods of food shortage. The shutdown of reproductive function during CR is consistent with this suggestion, but other features of the phenomenon are less consistent with this theory, and some have suggested that in rodents it may be mostly an artifact of domestication. CR induces profound effects on animals at all levels from the transcriptome to whole animal physiology and behavior. Animals under CR lose weight which is disproportionately contributed to by white adipose tissue. Generally animals on CR change their activity patterns so that they are more active prior to food delivery each day but total activity may be unchanged or reduced. Considerable debate has occurred over the effects of CR on resting metabolic rate (RMR). Total RMR declines, but as body mass and body composition also change it is unclear whether metabolism at the tissue level also declines, is unchanged or even increases. Body temperature universally decreases. Hunger is increased and does not seem to abate even with very long term restriction. Circulating adipokines are reduced reflecting the reduction in white adipose tissue (WAT) mass under restriction and there is a large reduction in circulating insulin and glucose levels. There are profound tissue level changes in metabolism with a

  13. Large-scale recording of astrocyte activity

    PubMed Central

    Nimmerjahn, Axel; Bergles, Dwight E.

    2015-01-01

    Astrocytes are highly ramified glial cells found throughout the central nervous system (CNS). They express a variety of neurotransmitter receptors that can induce widespread chemical excitation, placing these cells in an optimal position to exert global effects on brain physiology. However, the activity patterns of only a small fraction of astrocytes have been examined and techniques to manipulate their behavior are limited. As a result, little is known about how astrocytes modulate CNS function on synaptic, microcircuit, or systems levels. Here, we review current and emerging approaches for visualizing and manipulating astrocyte activity in vivo. Deciphering how astrocyte network activity is controlled in different physiological and pathological contexts is critical for defining their roles in the healthy and diseased CNS. PMID:25665733

  14. Caloric restriction impedes age-related decline of mitochondrial function and neuronal activity

    PubMed Central

    Lin, Ai-Ling; Coman, Daniel; Jiang, Lihong; Rothman, Douglas L; Hyder, Fahmeed

    2014-01-01

    Caloric restriction (CR) prolongs lifespan and retards many detrimental effects of aging, but its effect on brain mitochondrial function and neuronal activity—especially in healthy aging—remains unexplored. Here we measured rates of neuronal glucose oxidation and glutamate–glutamine neurotransmitter cycling in young control, old control (i.e., healthy aging), and old CR rats using in vivo nuclear magnetic resonance spectroscopy. We found that, compared with the young control, neuronal energy production and neurotransmission rates were significantly reduced in healthy aging, but were preserved in old CR rats. The results suggest that CR mitigated the age-related deceleration of brain physiology. PMID:24984898

  15. Retinoic Acid Activity in Undifferentiated Neural Progenitors Is Sufficient to Fulfill Its Role in Restricting Fgf8 Expression for Somitogenesis

    PubMed Central

    Cunningham, Thomas J.; Brade, Thomas; Sandell, Lisa L.; Lewandoski, Mark; Trainor, Paul A.; Colas, Alexandre; Mercola, Mark; Duester, Gregg

    2015-01-01

    Bipotent axial stem cells residing in the caudal epiblast during late gastrulation generate neuroectodermal and presomitic mesodermal progeny that coordinate somitogenesis with neural tube formation, but the mechanism that controls these two fates is not fully understood. Retinoic acid (RA) restricts the anterior extent of caudal fibroblast growth factor 8 (Fgf8) expression in both mesoderm and neural plate to control somitogenesis and neurogenesis, however it remains unclear where RA acts to control the spatial expression of caudal Fgf8. Here, we found that mouse Raldh2-/- embryos, lacking RA synthesis and displaying a consistent small somite defect, exhibited abnormal expression of key markers of axial stem cell progeny, with decreased Sox2+ and Sox1+ neuroectodermal progeny and increased Tbx6+ presomitic mesodermal progeny. The Raldh2-/- small somite defect was rescued by treatment with an FGF receptor antagonist. Rdh10 mutants, with a less severe RA synthesis defect, were found to exhibit a small somite defect and anterior expansion of caudal Fgf8 expression only for somites 1–6, with normal somite size and Fgf8 expression thereafter. Rdh10 mutants were found to lack RA activity during the early phase when somites are small, but at the 6-somite stage RA activity was detected in neural plate although not in presomitic mesoderm. Expression of a dominant-negative RA receptor in mesoderm eliminated RA activity in presomitic mesoderm but did not affect somitogenesis. Thus, RA activity in the neural plate is sufficient to prevent anterior expansion of caudal Fgf8 expression associated with a small somite defect. Our studies provide evidence that RA restriction of Fgf8 expression in undifferentiated neural progenitors stimulates neurogenesis while also restricting the anterior extent of the mesodermal Fgf8 mRNA gradient that controls somite size, providing new insight into the mechanism that coordinates somitogenesis with neurogenesis. PMID:26368825

  16. Functional characterization of neural-restrictive silencer element in mouse pituitary adenylate cyclase-activating polypeptide (PACAP) gene expression.

    PubMed

    Sugawara, Hideki; Tominaga, Aiko; Inoue, Kazuhiko; Takeda, Yasuo; Yamada, Katsushi; Miyata, Atsuro

    2014-11-01

    Pituitary adenylate cyclase-activating polypeptide (PACAP) is predominantly localized in the nervous system, but the underlying mechanism in its neuron-specific expression remains unclear. In addition to two neural-restrictive silencer-like element (NRSLE1 and 2), as reported previously, we have identified the third element in -1,601 to -1,581 bp from the translational initiation site of mouse PACAP gene and termed it as NRSLE3, of which, the sequence and location were highly conserved among mouse, rat, and human PACAP genes. In luciferase reporter assay, the deletion or site-directed mutagenesis of NRSLE3 in the reporter gene construct, driven by heterologous SV40 promoter, cancelled the repression of luciferase activity in non-neuronal Swiss-3T3 cells. Furthermore, its promoter activity was significantly repressed in Swiss-3T3 cells, but not in neuronal-differentiated PC12 cells. The electrophoretic mobility shift assay (EMSA) with nuclear extracts of Swiss-3T3 cells demonstrated a specific complex with NRSLE3 probe that exhibited the same migration with the neural-restrictive silencer element (NRSE) probe of rat type II sodium channel gene. During neuronal differentiation of PC12 cells, the increment of PACAP mRNA exhibited the correlation with that of REST4 mRNA, which is a neuron-specific variant form of neural-restrictive silencer factor (NRSF). In undifferentiated PC12 cells, trichostatin A (TSA), a histone deacetylase (HDAC) inhibitor, which indirectly inhibits NRSF-mediated gene silencing, increased PACAP mRNA level and attenuated the repression of promoter activity of 5' flanking region of mouse PACAP gene containing NRSLEs. These suggest that the NRSE-NRSF system implicates in the regulatory mechanism of neuron-specific expression of PACAP gene. PMID:24939248

  17. Reconsidering Physical Activity Restrictions for Mononephric Survivors of Childhood Cancer: A Report From the Children's Oncology Group.

    PubMed

    Okada, Maki; Hockenberry, Marilyn J; Koh, Chester J; Meeske, Kathleen A; Rangan, Kasey E; Rodgers, Cheryl; Rosenthal, Yael; Ruccione, Kathleen S; Freyer, David R

    2016-07-01

    Although traditional recommendations for mononephric childhood cancer survivors are to avoid contact sports in order to protect the remaining kidney, review of available evidence suggests that the majority of renal loss is caused by accidents not involving sports. An interdisciplinary team performed a review of the English literature published from 1999 to 2012 within the PubMed, Cochrane, Google Scholar, and National Guidelines Clearinghouse databases. The level of evidence and proposed recommendations were graded according to an established rubric and GRADE criteria. Our review found that kidney loss is most commonly caused by nonsports activities such as motor vehicle accidents and falls, implying that restrictions on sports-related activity in mononephric pediatric survivors are not well supported. This favors encouraging ordinary sports and related activities without restriction in mononephric childhood cancer survivors because the known benefits of exercise outweigh the exceedingly low risk of renal loss. Accordingly, activity recommendations for mononephric patients have been revised in the most current version of the Children's Oncology Group Long-term Follow-Up Guidelines for Survivors of Childhood, Adolescent and Young Adult Cancers. This has important implications for this and similar populations who may now undertake individual and organized sports without undue regard for their mononephric status. PMID:26589357

  18. The inner nuclear membrane protein Emerin regulates β-catenin activity by restricting its accumulation in the nucleus

    PubMed Central

    Markiewicz, Ewa; Tilgner, Katarzyna; Barker, Nick; van de Wetering, Mark; Clevers, Hans; Dorobek, Margareth; Hausmanowa-Petrusewicz, Irena; Ramaekers, Frans C S; Broers, Jos L V; Blankesteijn, W Matthijs; Salpingidou, Georgia; Wilson, Robert G; Ellis, Juliet A; Hutchison, Christopher J

    2006-01-01

    Emerin is a type II inner nuclear membrane (INM) protein of unknown function. Emerin function is likely to be important because, when it is mutated, emerin promotes both skeletal muscle and heart defects. Here we show that one function of Emerin is to regulate the flux of β-catenin, an important transcription coactivator, into the nucleus. Emerin interacts with β-catenin through a conserved adenomatous polyposis coli (APC)-like domain. When GFP-emerin is expressed in HEK293 cells, β-catenin is restricted to the cytoplasm and β-catenin activity is inhibited. In contrast, expression of an emerin mutant, lacking its APC-like domain (GFP-emerinΔ), dominantly stimulates β-catenin activity and increases nuclear accumulation of β-catenin. Human fibroblasts that are null for emerin have an autostimulatory growth phenotype. This unusual growth phenotype arises through enhanced nuclear accumulation and activity of β-catenin and can be replicated in wild-type fibroblasts by transfection with constitutively active β-catenin. Our results support recent findings that suggest that INM proteins can influence signalling pathways by restricting access of transcription coactivators to the nucleus. PMID:16858403

  19. Synergic chemoprevention with dietary carbohydrate restriction and supplementation of AMPK-activating phytochemicals: the role of SIRT1

    PubMed Central

    Choi, Min-Ah; Ro, Simon Weonsang; Yang, Woo Ick; Cho, Arthur E.H.; Ju, Hye-Lim; Baek, Sinhwa; Chung, Sook In; Kang, Won Jun; Yun, Mijin; Park, Jeon Han

    2016-01-01

    Calorie restriction or a low-carbohydrate diet (LCD) can increase life span in normal cells while inhibiting carcinogenesis. Various phytochemicals also have calorie restriction-mimetic anticancer properties. We investigated whether an isocaloric carbohydrate-restriction diet and AMP-activated protein kinase (AMPK)-activating phytochemicals induce synergic tumor suppression. We used a mixture of AMPK-activating phytochemical extracts including curcumin, quercetin, catechins, and resveratrol. Survival analysis was carried out in a B16F10 melanoma model fed a control diet (62.14% kcal carbohydrate, 24.65% kcal protein and 13.2% kcal fat), a control diet with multiple phytochemicals (MP), LCD (16.5, 55.2, and 28.3% kcal, respectively), LCD with multiple phytochemicals (LCDmp), a moderate-carbohydrate diet (MCD, 31.9, 62.4, and 5.7% kcal, respectively), or MCD with phytochemicals (MCDmp). Compared with the control group, MP, LCD, or MCD intervention did not produce survival benefit, but LCDmp (22.80±1.58 vs. 28.00±1.64 days, P=0.040) and MCDmp (23.80±1.08 vs. 30.13±2.29 days, P=0.008) increased the median survival time significantly. Suppression of the IGF-1R/PI3K/Akt/mTOR signaling, activation of the AMPK/SIRT1/LKB1pathway, and NF-κB suppression were the critical tumor-suppression mechanisms. In addition, SIRT1 suppressed proliferation of the B16F10 and A375SM cells under a low-glucose condition. Alterations in histone methylation within Pten and FoxO3a were observed after the MCDmp intervention. In the transgenic liver cancer model developed by hydrodynamic transfection of the HrasG12V and shp53, MCDmp and LCDmp interventions induced significant cancer-prevention effects. Microarray analysis showed that PPARα increased with decreased IL-6 and NF-κB within the hepatocytes after an MCDmp intervention. In conclusion, an isocaloric carbohydrate-restriction diet and natural AMPK-activating agents induce synergistic anticancer effects. SIRT1 acts as a

  20. Constitutively Active MAVS Inhibits HIV-1 Replication via Type I Interferon Secretion and Induction of HIV-1 Restriction Factors

    PubMed Central

    Gupta, Sachin; Termini, James M.; Issac, Biju; Guirado, Elizabeth; Stone, Geoffrey W.

    2016-01-01

    Type I interferon is known to inhibit HIV-1 replication through the induction of interferon stimulated genes (ISG), including a number of HIV-1 restriction factors. To better understand interferon-mediated HIV-1 restriction, we constructed a constitutively active form of the RIG-I adapter protein MAVS. Constitutive MAVS was generated by fusion of full length MAVS to a truncated form of the Epstein Barr virus protein LMP1 (ΔLMP1). Supernatant from ΔLMP1-MAVS-transfected 293T cells contained high levels of type I interferons and inhibited HIV replication in both TZM-bl and primary human CD4+ T cells. Supernatant from ΔLMP1-MAVS-transfected 293T cells also inhibited replication of VSV-G pseudotyped single cycle SIV in TZM-bl cells, suggesting restriction was post-entry and common to both HIV and SIV. Gene array analysis of ΔLMP1-MAVS-transfected 293T cells and trans-activated CD4+ T cells showed significant upregulation of ISG, including previously characterized HIV restriction factors Viperin, Tetherin, MxB, and ISG56. Interferon blockade studies implicated interferon-beta in this response. In addition to direct viral inhibition, ΔLMP1-MAVS markedly enhanced secretion of IFN-β and IL-12p70 by dendritic cells and the activation and maturation of dendritic cells. Based on this immunostimulatory activity, an adenoviral vector (Ad5) expressing ΔLMP1-MAVS was tested as a molecular adjuvant in an HIV vaccine mouse model. Ad5-Gag antigen combined with Ad5-ΔLMP1-MAVS enhanced control of vaccinia-gag replication in a mouse challenge model, with 4/5 animals showing undetectable virus following challenge. Overall, ΔLMP1-MAVS is a promising reagent to inhibit HIV-1 replication in infected tissues and enhance vaccine-mediated immune responses, while avoiding toxicity associated with systemic type I interferon administration. PMID:26849062

  1. p21-activated kinase 1 restricts tonic endocannabinoid signaling in the hippocampus

    PubMed Central

    Xia, Shuting; Zhou, Zikai; Leung, Celeste; Zhu, Yuehua; Pan, Xingxiu; Qi, Junxia; Morena, Maria; Hill, Matthew N; Xie, Wei; Jia, Zhengping

    2016-01-01

    PAK1 inhibitors are known to markedly improve social and cognitive function in several animal models of brain disorders, including autism, but the underlying mechanisms remain elusive. We show here that disruption of PAK1 in mice suppresses inhibitory neurotransmission through an increase in tonic, but not phasic, secretion of endocannabinoids (eCB). Consistently, we found elevated levels of anandamide (AEA), but not 2-arachidonoylglycerol (2-AG) following PAK1 disruption. This increased tonic AEA signaling is mediated by reduced cyclooxygenase-2 (COX-2), and COX-2 inhibitors recapitulate the effect of PAK1 deletion on GABAergic transmission in a CB1 receptor-dependent manner. These results establish a novel signaling process whereby PAK1 upregulates COX-2, reduces AEA and restricts tonic eCB-mediated processes. Because PAK1 and eCB are both critically involved in many other organ systems in addition to the brain, our findings may provide a unified mechanism by which PAK1 regulates these systems and their dysfunctions including cancers, inflammations and allergies. DOI: http://dx.doi.org/10.7554/eLife.14653.001 PMID:27296803

  2. p21-activated kinase 1 restricts tonic endocannabinoid signaling in the hippocampus.

    PubMed

    Xia, Shuting; Zhou, Zikai; Leung, Celeste; Zhu, Yuehua; Pan, Xingxiu; Qi, Junxia; Morena, Maria; Hill, Matthew N; Xie, Wei; Jia, Zhengping

    2016-01-01

    PAK1 inhibitors are known to markedly improve social and cognitive function in several animal models of brain disorders, including autism, but the underlying mechanisms remain elusive. We show here that disruption of PAK1 in mice suppresses inhibitory neurotransmission through an increase in tonic, but not phasic, secretion of endocannabinoids (eCB). Consistently, we found elevated levels of anandamide (AEA), but not 2-arachidonoylglycerol (2-AG) following PAK1 disruption. This increased tonic AEA signaling is mediated by reduced cyclooxygenase-2 (COX-2), and COX-2 inhibitors recapitulate the effect of PAK1 deletion on GABAergic transmission in a CB1 receptor-dependent manner. These results establish a novel signaling process whereby PAK1 upregulates COX-2, reduces AEA and restricts tonic eCB-mediated processes. Because PAK1 and eCB are both critically involved in many other organ systems in addition to the brain, our findings may provide a unified mechanism by which PAK1 regulates these systems and their dysfunctions including cancers, inflammations and allergies. PMID:27296803

  3. Restriction to large-scale gene flow vs. regional panmixia among cold seep Escarpia spp. (Polychaeta, Siboglinidae).

    PubMed

    Cowart, Dominique A; Huang, Chunya; Arnaud-Haond, Sophie; Carney, Susan L; Fisher, Charles R; Schaeffer, Stephen W

    2013-08-01

    The history of colonization and dispersal in fauna distributed among deep-sea chemosynthetic ecosystems remains enigmatic and poorly understood because of an inability to mark and track individuals. A combination of molecular, morphological and environmental data improves understanding of spatial and temporal scales at which panmixia, disruption of gene flow or even speciation may occur. Vestimentiferan tubeworms of the genus Escarpia are important components of deep -sea cold seep ecosystems, as they provide long-term habitat for many other taxa. Three species of Escarpia, Escarpia spicata [Gulf of California (GoC)], Escarpia laminata [Gulf of Mexico (GoM)] and Escarpia southwardae (West African Cold Seeps), have been described based on morphology, but are not discriminated through the use of mitochondrial markers (cytochrome oxidase subunit 1; large ribosomal subunit rDNA, 16S; cytochrome b). Here, we also sequenced the exon-primed intron-crossing Haemoglobin subunit B2 intron and genotyped 28 microsatellites to (i) determine the level of genetic differentiation, if any, among the three geographically separated entities and (ii) identify possible population structure at the regional scale within the GoM and West Africa. Results at the global scale support the occurrence of three genetically distinct groups. At the regional scale among eight sampling sites of E. laminata (n = 129) and among three sampling sites of E. southwardae (n = 80), no population structure was detected. These findings suggest that despite the patchiness and isolation of seep habitats, connectivity is high on regional scales. PMID:23879204

  4. Effects of T592 phosphomimetic mutations on tetramer stability and dNTPase activity of SAMHD1 can not explain the retroviral restriction defect.

    PubMed

    Bhattacharya, Akash; Wang, Zhonghua; White, Tommy; Buffone, Cindy; Nguyen, Laura A; Shepard, Caitlin N; Kim, Baek; Demeler, Borries; Diaz-Griffero, Felipe; Ivanov, Dmitri N

    2016-01-01

    SAMHD1, a dNTP triphosphohydrolase, contributes to interferon signaling and restriction of retroviral replication. SAMHD1-mediated retroviral restriction is thought to result from the depletion of cellular dNTP pools, but it remains controversial whether the dNTPase activity of SAMHD1 is sufficient for restriction. The restriction ability of SAMHD1 is regulated in cells by phosphorylation on T592. Phosphomimetic mutations of T592 are not restriction competent, but appear intact in their ability to deplete cellular dNTPs. Here we use analytical ultracentrifugation, fluorescence polarization and NMR-based enzymatic assays to investigate the impact of phosphomimetic mutations on SAMHD1 tetramerization and dNTPase activity in vitro. We find that phosphomimetic mutations affect kinetics of tetramer assembly and disassembly, but their effects on tetramerization equilibrium and dNTPase activity are insignificant. In contrast, the Y146S/Y154S dimerization-defective mutant displays a severe dNTPase defect in vitro, but is indistinguishable from WT in its ability to deplete cellular dNTP pools and to restrict HIV replication. Our data suggest that the effect of T592 phosphorylation on SAMHD1 tetramerization is not likely to explain the retroviral restriction defect, and we hypothesize that enzymatic activity of SAMHD1 is subject to additional cellular regulatory mechanisms that have not yet been recapitulated in vitro. PMID:27511536

  5. Effects of T592 phosphomimetic mutations on tetramer stability and dNTPase activity of SAMHD1 can not explain the retroviral restriction defect

    PubMed Central

    Bhattacharya, Akash; Wang, Zhonghua; White, Tommy; Buffone, Cindy; Nguyen, Laura A.; Shepard, Caitlin N.; Kim, Baek; Demeler, Borries; Diaz-Griffero, Felipe; Ivanov, Dmitri N.

    2016-01-01

    SAMHD1, a dNTP triphosphohydrolase, contributes to interferon signaling and restriction of retroviral replication. SAMHD1-mediated retroviral restriction is thought to result from the depletion of cellular dNTP pools, but it remains controversial whether the dNTPase activity of SAMHD1 is sufficient for restriction. The restriction ability of SAMHD1 is regulated in cells by phosphorylation on T592. Phosphomimetic mutations of T592 are not restriction competent, but appear intact in their ability to deplete cellular dNTPs. Here we use analytical ultracentrifugation, fluorescence polarization and NMR-based enzymatic assays to investigate the impact of phosphomimetic mutations on SAMHD1 tetramerization and dNTPase activity in vitro. We find that phosphomimetic mutations affect kinetics of tetramer assembly and disassembly, but their effects on tetramerization equilibrium and dNTPase activity are insignificant. In contrast, the Y146S/Y154S dimerization-defective mutant displays a severe dNTPase defect in vitro, but is indistinguishable from WT in its ability to deplete cellular dNTP pools and to restrict HIV replication. Our data suggest that the effect of T592 phosphorylation on SAMHD1 tetramerization is not likely to explain the retroviral restriction defect, and we hypothesize that enzymatic activity of SAMHD1 is subject to additional cellular regulatory mechanisms that have not yet been recapitulated in vitro. PMID:27511536

  6. Plasma membrane restricted RhoGEF activity is sufficient for RhoA-mediated actin polymerization

    PubMed Central

    van Unen, Jakobus; Reinhard, Nathalie R.; Yin, Taofei; Wu, Yi I.; Postma, Marten; Gadella, Theodorus W.J.; Goedhart, Joachim

    2015-01-01

    The small GTPase RhoA is involved in cell morphology and migration. RhoA activity is tightly regulated in time and space and depends on guanine exchange factors (GEFs). However, the kinetics and subcellular localization of GEF activity towards RhoA are poorly defined. To study the mechanism underlying the spatiotemporal control of RhoA activity by GEFs, we performed single cell imaging with an improved FRET sensor reporting on the nucleotide loading state of RhoA. By employing the FRET sensor we show that a plasma membrane located RhoGEF, p63RhoGEF, can rapidly activate RhoA through endogenous GPCRs and that localized RhoA activity at the cell periphery correlates with actin polymerization. Moreover, synthetic recruitment of the catalytic domain derived from p63RhoGEF to the plasma membrane, but not to the Golgi apparatus, is sufficient to activate RhoA. The synthetic system enables local activation of endogenous RhoA and effectively induces actin polymerization and changes in cellular morphology. Together, our data demonstrate that GEF activity at the plasma membrane is sufficient for actin polymerization via local RhoA signaling. PMID:26435194

  7. CD252 regulates mast cell mediated, CD1d-restricted NKT-cell activation in mice.

    PubMed

    Gonzalez Roldan, Nestor; Orinska, Zane; Ewers, Hanno; Bulfone-Paus, Silvia

    2016-02-01

    The interaction between tissue-resident mast cells (MCs) and recruited immune cells contributes to tissue immunosurveillance. However, the cells, mechanisms, and receptors involved in this crosstalk remain ill defined. Invariant natural killer T (iNKT) cells are CD1d-restricted innate lymphocytes that recognize glycolipid antigens and have emerged as critical players in immunity. Here, we show that primary mouse peritoneal MCs express surface CD1d, which is upregulated in vivo following administration of alpha-galactosylceramide. In contrast, in BM-derived MCs CD1d was found to be stored intracellularly and to relocate at the cell surface upon IgE-mediated degranulation. Activated BM-derived MCs expressing surface CD1d and loaded with alpha-galactosylceramide were found to induce iNKT-cell proliferation and the release of IFN-γ, IL-13, and IL-4 in a CD1d-restricted manner. Moreover, the costimulatory molecules CD48, CD137L, CD252, CD274, and CD275 affected MC-induced IFN-γ release and iNKT-cell proliferation. Interestingly, among the costimulatory molecules, CD48 and CD252 exhibited a distinctly regulatory activity on iNKT-cell release of both IFN-γ and IL-13. In conclusion, we demonstrate that the crosstalk between MCs and iNKT cells may regulate inflammatory immune responses. PMID:26564814

  8. A Natural Polymorphism in rDNA Replication Origins Links Origin Activation with Calorie Restriction and Lifespan

    PubMed Central

    Kwan, Elizabeth X.; Foss, Eric J.; Tsuchiyama, Scott; Alvino, Gina M.; Kruglyak, Leonid; Kaeberlein, Matt; Raghuraman, M. K.; Brewer, Bonita J.; Kennedy, Brian K.; Bedalov, Antonio

    2013-01-01

    Aging and longevity are complex traits influenced by genetic and environmental factors. To identify quantitative trait loci (QTLs) that control replicative lifespan, we employed an outbred Saccharomyces cerevisiae model, generated by crossing a vineyard and a laboratory strain. The predominant QTL mapped to the rDNA, with the vineyard rDNA conferring a lifespan increase of 41%. The lifespan extension was independent of Sir2 and Fob1, but depended on a polymorphism in the rDNA origin of replication from the vineyard strain that reduced origin activation relative to the laboratory origin. Strains carrying vineyard rDNA origins have increased capacity for replication initiation at weak plasmid and genomic origins, suggesting that inability to complete genome replication presents a major impediment to replicative lifespan. Calorie restriction, a conserved mediator of lifespan extension that is also independent of Sir2 and Fob1, reduces rDNA origin firing in both laboratory and vineyard rDNA. Our results are consistent with the possibility that calorie restriction, similarly to the vineyard rDNA polymorphism, modulates replicative lifespan through control of rDNA origin activation, which in turn affects genome replication dynamics. PMID:23505383

  9. Junctionally restricted RhoA activity is necessary for apical constriction during phase 2 inner ear placode invagination.

    PubMed

    Sai, Xiaorei; Yonemura, Shigenobu; Ladher, Raj K

    2014-10-15

    After induction, the inner ear is transformed from a superficially located otic placode into an epithelial vesicle embedded in the mesenchyme of the head. Invagination of this epithelium is biphasic: phase 1 involves the expansion of the basal aspect of the otic cells, and phase 2, the constriction of their apices. Apical constriction is important not only for otic invagination, but also the invagination of many other epithelia; however, its molecular basis is still poorly understood. Here we show that phase 2 otic morphogenesis, like phase 1 morphogenesis, results from the activation of myosin-II. However unlike the actin depolymerising activity observed basally, active myosin-II results in actomyosin contractility. Myosin-II activation is triggered by the accumulation of the planar cell polarity (PCP) core protein, Celsr1 in apical junctions (AJ). Apically polarized Celsr1 orients and recruits the Rho Guanine exchange factor (GEF) ArhGEF11 to apical junctions, thus restricting RhoA activity to the junctional membrane where it activates the Rho kinase ROCK. We suggest that myosin-II and RhoA activation results in actomyosin dependent constriction in an apically polarised manner driving otic epithelium invagination. PMID:25173873

  10. Serotonin suppresses food anticipatory activity and synchronizes the food-entrainable oscillator during time-restricted feeding.

    PubMed

    Rozenblit-Susan, Sigal; Chapnik, Nava; Genzer, Yoni; Froy, Oren

    2016-01-15

    The serotonergic and circadian systems are intertwined as serotonin modulates the response of the central brain suprachiasmatic nuclei (SCN) clock to light. Time-restricted feeding (RF) is characterized by increased food anticipatory activity (FAA) and controlled by the food-entrainable oscillator (FEO) rather than the SCN. Our objective was to test whether serotonin affects the FEO. Mice were treated with the selective serotonin reuptake inhibitor (SSRI) fluvoxamine (FLX) or the tryptophan hydroxylase inhibitor parachlorophenylalanine (PCPA) and locomotor activity under ad libitum feeding, RF and different lighting conditions was monitored. Under AL, FLX administration did not affect 24-h locomotor activity, while mice treated with PCPA exhibited increased activity. RF-FLX-treated mice showed less FAA 2h before food availability (ZT2-ZT4) compared to RF- or RF-PCPA-fed mice. Under DD, RF-PCPA-treated mice displayed increased activity, as was seen under LD conditions. Surprisingly, RF-PCPA-treated mice showed free running in the FAA component. These results emphasize the role of serotonin in SCN-mediated activity inhibition and FEO entrainment and activity. PMID:26467604

  11. The Validation of the Active Learning in Health Professions Scale

    ERIC Educational Resources Information Center

    Kammer, Rebecca; Schreiner, Laurie; Kim, Young K.; Denial, Aurora

    2015-01-01

    There is a need for an assessment tool for evaluating the effectiveness of active learning strategies such as problem-based learning in promoting deep learning and clinical reasoning skills within the dual environments of didactic and clinical settings in health professions education. The Active Learning in Health Professions Scale (ALPHS)…

  12. Psychometric Properties of the Commitment to Physical Activity Scale

    ERIC Educational Resources Information Center

    DeBate, Rita DiGioacchino; Huberty, Jennifer; Pettee, Kelley

    2009-01-01

    Objective: To assess psychometric properties of the Commitment to Physical Activity Scale (CPAS). Methods: Girls in third to fifth grades (n = 932) completed the CPAS before and after a physical activity intervention. Psychometric measures included internal consistency, factor analysis, and concurrent validity. Results: Three CPAS factors emerged:…

  13. Francisella tularensis Catalase Restricts Immune Function by Impairing TRPM2 Channel Activity.

    PubMed

    Shakerley, Nicole L; Chandrasekaran, Akshaya; Trebak, Mohamed; Miller, Barbara A; Melendez, J Andrés

    2016-02-19

    As an innate defense mechanism, macrophages produce reactive oxygen species that weaken pathogens and serve as secondary messengers involved in immune function. The Gram-negative bacterium Francisella tularensis utilizes its antioxidant armature to limit the host immune response, but the mechanism behind this suppression is not defined. Here we establish that F. tularensis limits Ca(2+) entry in macrophages, thereby limiting actin reorganization and IL-6 production in a redox-dependent fashion. Wild type (live vaccine strain) or catalase-deficient F. tularensis (ΔkatG) show distinct profiles in their H2O2 scavenging rates, 1 and 0.015 pm/s, respectively. Murine alveolar macrophages infected with ΔkatG display abnormally high basal intracellular Ca(2+) concentration that did not increase further in response to H2O2. Additionally, ΔkatG-infected macrophages displayed limited Ca(2+) influx in response to ionomycin, as a result of ionophore H2O2 sensitivity. Exogenously added H2O2 or H2O2 generated by ΔkatG likely oxidizes ionomycin and alters its ability to transport Ca(2+). Basal increases in cytosolic Ca(2+) and insensitivity to H2O2-mediated Ca(2+) entry in ΔkatG-infected cells are reversed by the Ca(2+) channel inhibitors 2-aminoethyl diphenylborinate and SKF-96365. 2-Aminoethyl diphenylborinate but not SKF-96365 abrogated ΔkatG-dependent increases in macrophage actin remodeling and IL-6 secretion, suggesting a role for H2O2-mediated Ca(2+) entry through the transient receptor potential melastatin 2 (TRPM2) channel in macrophages. Indeed, increases in basal Ca(2+), actin polymerization, and IL-6 production are reversed in TRPM2-null macrophages infected with ΔkatG. Together, our findings provide compelling evidence that F. tularensis catalase restricts reactive oxygen species to temper macrophage TRPM2-mediated Ca(2+) signaling and limit host immune function. PMID:26679996

  14. Psychological, Physical and Sensory Correlates of Fear of Falling and Consequent Activity Restriction in the Elderly: The InCHIANTI Study

    PubMed Central

    Deshpande, Nandini; Metter, E. Jeffery; Bandinelli, Stefania; Lauretani, Fulvio; Windham, B. Gwen; Ferrucci, Luigi

    2008-01-01

    OBJECTIVE To identify psychological, physical and sensory function parameters that are specifically associated with fear of falling (FF) and fear-induced activity restriction in a population-based sample of older adults. DESIGN FF, fear-induced activity restriction, cognition, depression, personal mastery, chair stand performance, standing balance, lower limb and grip strength, visual acuity and contrast sensitivity and vibrotactile sensitivity were evaluated in the population-based older cohort (n=926, age ≥ 65) enrolled in the InCHIANTI study. RESULTS Nearly 50% participants reported FF. Of these, 65% reported some activity restriction. Personal mastery (p< .001) and chair standing performance (p= .001) were independently associated with FF. In those who did not have depression, personal mastery, standing balance, lower limb strength and visual contrast sensitivity were associated with activity restriction (p<.001 to .011). In those who were depressed, Total FF was the major factor strongly associated with activity restriction (p< .001) with marginal but significant association for cognition (p= .027) and standing balance (p= .015). CONCLUSION Psychological and physical factors are independently associated with FF. Presence of depression possibly modulates what factors in addition to fear of falling affect fear-induced activity restriction. A longitudinal study is warranted to substantiate causal relationships. PMID:18174852

  15. The effects of lighting conditions and food restriction paradigms on locomotor activity of common spiny mice, Acomys cahirinus

    PubMed Central

    2012-01-01

    Background An endogenous circadian clock controls locomotor activity in common spiny mice (Acomys cahirinus). However, little is known about the effects of constant light (LL) on this activity or about the existence of an additional food entrainable clock. A series of experiments were performed to investigate the effects of LL and DD on tau and activity levels. Methods Spiny mice were housed individually and their running wheel activity monitored. One group of mice was exposed to LD, DD and several intensities of LL. Another group was exposed to a restricted feeding (RF) paradigm in light: dark (LD) during one hour before the L to D transition. Significance of rhythmicity was assessed using Lomb-Scargle periodograms. Results In LD all animals exhibited nocturnal activity rhythms that persisted in DD. When animals were exposed to RF (during L), all of these animals (n = 11) demonstrated significant food anticipatory activity as well as an increase in diurnal activity. This increase in diurnal activity persisted in 4/11 animals during subsequent ad libitum conditions. Under LL conditions, the locomotor rhythms of 2/11 animals appeared to entrain to RF. When animals were exposed to sequentially increasing LL intensities, rhythmicity persisted and, while activity decreased significantly, the free-running period was relatively unaffected. In addition, the period in LL was significantly longer than the period in DD. Exposure to LL also induced long-term changes (after-effects) on period and activity when animals were again exposed to DD. Conclusions Overall these studies demonstrate clear and robust circadian rhythms of wheel-running in A. cahirinus. In addition, LL clearly inhibited activity in this species and induced after-effects. The results also confirm the presence of a food entrainable oscillator in this species. PMID:22958374

  16. Repetitive and Retinotopically Restricted Activation of the Dorsal Lateral Geniculate Nucleus with Optogenetics

    PubMed Central

    Castonguay, Alexandre; Thomas, Sébastien; Lesage, Frédéric; Casanova, Christian

    2014-01-01

    Optogenetics allows the control of cellular activity using focused delivery of light pulses. In neuroscience, optogenetic protocols have been shown to efficiently inhibit or stimulate neuronal activity with a high temporal resolution. Among the technical challenges associated with the use of optogenetics, one is the ability to target a spatially specific population of neurons in a given brain structure. To address this issue, we developed a side-illuminating optical fiber capable of delivering light to specific sites in a target nucleus with added flexibility through rotation and translation of the fiber and by varying the output light power. The designed optical fiber was tested in vivo in visual structures of ChR2-expressing transgenic mice. To assess the spatial extent of neuronal activity modulation, we took advantage of the hallmark of the visual system: its retinotopic organization. Indeed, the relative position of ganglion cells in the retina is transposed in the cellular topography of both the dorsal lateral geniculate nucleus (LGN) in the thalamus and the primary visual cortex (V1). The optical fiber was inserted in the LGN and by rotating it with a motor, it was possible to sequentially activate different neuronal populations within this structure. The activation of V1 neurons by LGN projections was recorded using intrinsic optical imaging. Increasing light intensity (from 1.4 to 8.9 mW/mm2) led to increasing activation surfaces in V1. Optogenetic stimulation of the LGN at different translational and rotational positions was associated with different activation maps in V1. The position and/or orientation of the fiber inevitably varied across experiments, thus limiting the capacity to pool data. With the optogenetic design presented here, we demonstrate for the first time a transitory and spatially-concise activation of a deep neuronal structure. The optogenetic design presented here thus opens a promising avenue for studying the function of deep brain

  17. Repetitive and retinotopically restricted activation of the dorsal lateral geniculate nucleus with optogenetics.

    PubMed

    Castonguay, Alexandre; Thomas, Sébastien; Lesage, Frédéric; Casanova, Christian

    2014-01-01

    Optogenetics allows the control of cellular activity using focused delivery of light pulses. In neuroscience, optogenetic protocols have been shown to efficiently inhibit or stimulate neuronal activity with a high temporal resolution. Among the technical challenges associated with the use of optogenetics, one is the ability to target a spatially specific population of neurons in a given brain structure. To address this issue, we developed a side-illuminating optical fiber capable of delivering light to specific sites in a target nucleus with added flexibility through rotation and translation of the fiber and by varying the output light power. The designed optical fiber was tested in vivo in visual structures of ChR2-expressing transgenic mice. To assess the spatial extent of neuronal activity modulation, we took advantage of the hallmark of the visual system: its retinotopic organization. Indeed, the relative position of ganglion cells in the retina is transposed in the cellular topography of both the dorsal lateral geniculate nucleus (LGN) in the thalamus and the primary visual cortex (V1). The optical fiber was inserted in the LGN and by rotating it with a motor, it was possible to sequentially activate different neuronal populations within this structure. The activation of V1 neurons by LGN projections was recorded using intrinsic optical imaging. Increasing light intensity (from 1.4 to 8.9 mW/mm²) led to increasing activation surfaces in V1. Optogenetic stimulation of the LGN at different translational and rotational positions was associated with different activation maps in V1. The position and/or orientation of the fiber inevitably varied across experiments, thus limiting the capacity to pool data. With the optogenetic design presented here, we demonstrate for the first time a transitory and spatially-concise activation of a deep neuronal structure. The optogenetic design presented here thus opens a promising avenue for studying the function of deep brain

  18. Disability due to restrictions in childhood epilepsy.

    PubMed

    Carpay, H A; Vermeulen, J; Stroink, H; Brouwer, O F; Peters, A C; van Donselaar, C A; Aldenkamp, A P; Arts, W F

    1997-08-01

    Parents and doctors impose restrictions on children with epilepsy to avoid seizure-related injuries. We intended to quantify disability due to such restrictions by using a newly developed parent-completed 10-item scale (The Hague Restrictions in Childhood Epilepsy Scale, HARCES). Parents reported disability on at least one item of the HARCES in 83% of 122 children with epilepsy and a remission from seizures for less than 1 year. Psychometric analysis of the scale's reliability demonstrated good internal consistency and retest stability. Its validity was supported by the association between HARCES scores and the physicians' advice imposing restrictions. We found no substantial association with such variables as seizure type, short-term remission, or seizure activity. These findings suggest that in children with recurrent seizures, restrictions were probably not optimally adapted to seizure-related risks. A repeat test after 1 year showed that a seizure remission of more than 1 year substantially reduced restrictions, which is probably associated with an improvement in quality of life. PMID:9295847

  19. Activation of different Stat5 isoforms contributes to cell-type-restricted signaling in response to interferons.

    PubMed Central

    Meinke, A; Barahmand-Pour, F; Wöhrl, S; Stoiber, D; Decker, T

    1996-01-01

    Tyrosine phosphorylation and activation of the transcription factor Stat5 occur in response to stimuli like granulocyte-macrophage colony-stimulating factor, interleukin-3, or erythropoietin that stimulate both proliferation and differentiation of hematopoietic cells. It is unclear whether Stat5 is part of a proliferative response or part of the events leading to cellular differentiation. Here we report that agents promoting differentiation but not proliferation of hematopoietic cells, like phorbol ester or both types of interferons (IFNs), activate Stat5 in promonocytic U937 cells. Both IFN types caused tyrosine phosphorylation and DNA binding of predominantly one Stat5 isoform (Stat5a) despite expression of both Stat5a and Stat5b proteins. Monocytic differentiation of U937 cells led to a strong decrease in IFN-gamma-mediated activation of Stat5 but not of Stat1. Transactivation of Stat5-target genes occurred in response to IFN-gamma, which activates both Stat5 and Stat1, but not in response to granulocyte-macrophage colony-stimulating factor, which activates only Stat5. Tyrosine phosphorylation of Stat5 is not generally part of the IFN response. IFN-gamma did not cause Stat5 activation in HeLa cells, despite the expression of both Stat5 isoforms at similar levels. By contrast, IFN-alpha caused tyrosine phosphorylation and DNA binding of exclusively the b isoform of Stat5, and activated Stat5b formed a DNA binding activity previously found in HeLa cells and designated IFN-alpha activation factor 2. Taken together, our results demonstrate that ligand binding of IFN receptors leads to an isoform-specific activation of Stat5 in a restricted number of cell lineages. Moreover, they suggest that Stat5 might be part of the differentiation response of myeloid cells. PMID:8943349

  20. Apigenin Restricts FMDV Infection and Inhibits Viral IRES Driven Translational Activity

    PubMed Central

    Qian, Suhong; Fan, Wenchun; Qian, Ping; Zhang, Dong; Wei, Yurong; Chen, Huanchun; Li, Xiangmin

    2015-01-01

    Foot-and-mouth disease (FMD) is a highly contagious disease of domestic and wild ruminants that is caused by FMD virus (FMDV). FMD outbreaks have occurred in livestock-containing regions worldwide. Apigenin, which is a flavonoid naturally existing in plant, possesses various pharmacological effects, including anti-inflammatory, anticancer, antioxidant and antiviral activities. Results show that apigenin can inhibit FMDV-mediated cytopathogenic effect and FMDV replication in vitro. Further studies demonstrate the following: (i) apigenin inhibits FMDV infection at the viral post-entry stage; (ii) apigenin does not exhibit direct extracellular virucidal activity; and (iii) apigenin interferes with the translational activity of FMDV driven by internal ribosome entry site. Studies on applying apigein in vivo are required for drug development and further identification of potential drug targets against FDMV infection. PMID:25835532

  1. A continuous enzyme-coupled assay for triphosphohydrolase activity of HIV-1 restriction factor SAMHD1.

    PubMed

    Arnold, Laurence H; Kunzelmann, Simone; Webb, Martin R; Taylor, Ian A

    2015-01-01

    The development of deoxynucleoside triphosphate (dNTP)-based drugs requires a quantitative understanding of any inhibition, activation, or hydrolysis by off-target cellular enzymes. SAMHD1 is a regulatory dNTP-triphosphohydrolase that inhibits HIV-1 replication in human myeloid cells. We describe here an enzyme-coupled assay for quantifying the activation, inhibition, and hydrolysis of dNTPs, nucleotide analogues, and nucleotide analogue inhibitors by triphosphohydrolase enzymes. The assay facilitates mechanistic studies of triphosphohydrolase enzymes and the quantification of off-target effects of nucleotide-based antiviral and chemotherapeutic agents. PMID:25331707

  2. Large-scale filament formation inhibits the activity of CTP synthetase

    PubMed Central

    Barry, Rachael M; Bitbol, Anne-Florence; Lorestani, Alexander; Charles, Emeric J; Habrian, Chris H; Hansen, Jesse M; Li, Hsin-Jung; Baldwin, Enoch P; Wingreen, Ned S; Kollman, Justin M; Gitai, Zemer

    2014-01-01

    CTP Synthetase (CtpS) is a universally conserved and essential metabolic enzyme. While many enzymes form small oligomers, CtpS forms large-scale filamentous structures of unknown function in prokaryotes and eukaryotes. By simultaneously monitoring CtpS polymerization and enzymatic activity, we show that polymerization inhibits activity, and CtpS's product, CTP, induces assembly. To understand how assembly inhibits activity, we used electron microscopy to define the structure of CtpS polymers. This structure suggests that polymerization sterically hinders a conformational change necessary for CtpS activity. Structure-guided mutagenesis and mathematical modeling further indicate that coupling activity to polymerization promotes cooperative catalytic regulation. This previously uncharacterized regulatory mechanism is important for cellular function since a mutant that disrupts CtpS polymerization disrupts E. coli growth and metabolic regulation without reducing CTP levels. We propose that regulation by large-scale polymerization enables ultrasensitive control of enzymatic activity while storing an enzyme subpopulation in a conformationally restricted form that is readily activatable. DOI: http://dx.doi.org/10.7554/eLife.03638.001 PMID:25030911

  3. 15 CFR 744.6 - Restrictions on certain activities of U.S. persons.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... activities unrelated to exports. No U.S. person shall, without a license from BIS: (i) Perform any contract... 740 of the EAR); or (ii) Perform any contract, service, or employment that the U.S. person knows will... apply to the prohibitions described in paragraphs (a) and (b) of this section. (e) License...

  4. 20 CFR 668.350 - Are there any restrictions on allowable activities?

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... LABOR (CONTINUED) INDIAN AND NATIVE AMERICAN PROGRAMS UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT..., as described in WIA section 181(d) and 20 CFR 667.268. (e) INA grantees must only use WIA funds for activities which are in addition to those that would otherwise be available to the Native American...

  5. 20 CFR 668.350 - Are there any restrictions on allowable activities?

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... LABOR (CONTINUED) INDIAN AND NATIVE AMERICAN PROGRAMS UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT..., as described in WIA section 181(d) and 20 CFR 667.268. (e) INA grantees must only use WIA funds for activities which are in addition to those that would otherwise be available to the Native American...

  6. 20 CFR 668.350 - Are there any restrictions on allowable activities?

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... LABOR (CONTINUED) INDIAN AND NATIVE AMERICAN PROGRAMS UNDER TITLE I OF THE WORKFORCE INVESTMENT ACT..., as described in WIA section 181(d) and 20 CFR 667.268. (e) INA grantees must only use WIA funds for activities which are in addition to those that would otherwise be available to the Native American...

  7. 20 CFR 668.350 - Are there any restrictions on allowable activities?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    .... 195(4).) (d) INA grantees are prohibited from using funds to encourage the relocation of a business, as described in WIA section 181(d) and 20 CFR 667.268. (e) INA grantees must only use WIA funds for... way affect union organizing. (g) Under 20 CFR 667.266, sectarian activities involving WIA...

  8. The Geriatric Hand: Correlation of Hand-Muscle Function and Activity Restriction in Elderly

    ERIC Educational Resources Information Center

    Incel, Nurgul Arinci; Sezgin, Melek; As, Ismet; Cimen, Ozlem Bolgen; Sahin, Gunsah

    2009-01-01

    On the basis of the importance of hand manipulation in activities of daily living (ADL), deterioration of hand function because of various factors reduces quality and independence of life of the geriatric population. The aim of this study was to identify age-induced changes in manual function and to quantify the correlations between hand-muscle…

  9. Calcium metabolism in bone and teeth of rats during exposure to restriction of motor activity and to swimming exercise.

    PubMed

    Zorbas, Y G; Charapakhin, K P; Kuznetsov, N A; Kakurin, V J

    1999-06-01

    The effects of motor activity restriction for 90 days (hypokinesia, HK) and swimming training (T) on calcium metabolism in rat bones and teeth were evaluated. Male Wistar rats were distributed in four groups: untrained vivarium control rats (UVCR), untrained hypokinetic rats (UHKR), trained hypokinetic rats (THKR) and trained vivarium control rats (TVCR). Hypokinesia was obtained keeping the animals for 90 days in small individual cages which restricted their movements in all directions without hindering food and water intakes. Rats of THKR and TVCR were forced to swim for 15 to 90 minutes everyday. On the 1st, 7th, 15th day of a prehypokinetic period and on the 5th, 10th, 20th, 40th, 60th and 90th day of the hypokinetic period, six rats of each group were decapitated. Radioactive calcium was injected to the animals 70 days before autopsy. Calcium and phosphorus in serum, bones (molars, incisors, upper and lower jaws, parietal, scapular, clavicle, pelvic and tibial bones) and in the respective ash residues were measured. Body and bone weights, and radioactive calcium were also determined. Under prolonged exposure to HK (THKR and UHKR groups), bone weights and bone and ash Ca and P concentrations decreased, whereas serum Ca and P and 45Ca resorption increased, in comparison to the respective values in the UVCR and TVCR groups. Swimming exercise apparently did not modify calcium metabolism in the hypokinetic or control rats. PMID:10517263

  10. Synthesis and Antitumor Activity of 1,5-Disubstituted 1,2,4-Triazoles as Cis-Restricted Combretastatin Analogues

    PubMed Central

    Romagnoli, Romeo; Baraldi, Pier Giovanni; Cruz-Lopez, Olga; Lopez Cara, Carlota; Carrion, Maria Dora; Brancale, Andrea; Hamel, Ernest; Chen, Longchuan; Bortolozzi, Roberta; Basso, Giuseppe; Viola, Giampietro

    2010-01-01

    A series of 1-aryl-5-(3′,4′,5′-trimethoxyphenyl) derivatives and their related 1-(3′,4′,5′-trimethoxyphenyl)-5-aryl-1,2,4-triazoles, designed as cis-restricted combretastatin analogues, were synthesized and evaluated for antiproliferative activity, inhibitory effects on tubulin polymerization, cell cycle effects, and apoptosis induction. Their activity was greater than, or comparable with, that of the reference compound CA-4. Flow cytometry studies showed that HeLa and Jurkat cells treated with the most active compounds 4l and 4o were arrested in the G2/M phase of the cell cycle in a concentration dependent manner. This effect was accompanied by apoptosis of the cells, mitochondrial depolarization, generation of reactive oxygen species, activation of caspase-3, and PARP cleavage. Compound 4l was also shown to have potential antivascular activity, since it induced endothelial cell shape change in vitro and disrupted the sprouting of endothelial cells in the chick aortic ring assay. PMID:20420439

  11. Enzymes of Glycerol and Glyceraldehyde Metabolism in Mouse Liver: Effects of Caloric Restriction and Age on Activities

    PubMed Central

    Hagopian, Kevork; Ramsey, Jon J.; Weindruch, Richard

    2008-01-01

    Synopsis The influence of caloric restriction on hepatic glyceraldehyde and glycerol metabolizing enzyme activities of young and old mice were studied. Glycerol kinase and cytoplasmic glycerol-3-phosphate dehydrogenase activities were increased in both young and old CR mice when compared to controls, while triokinase increased only in old CR mice. Aldehyde dehydrogenase and aldehyde reductase activities in both young and old CR were unchanged by CR. Mitochondrial glycerol-3-phosphate dehydrogenase showed a trend towards an increased activity in old CR mice, while a trend towards a decreased activity in alcohol dehydrogenase was observed in both young and old CR mice. Serum glycerol levels decreased in young and old CR mice. Therefore, increases in glycerol kinase and glycerol-3-phosphate dehydrogenase were associated with a decrease in fasting blood glycerol levels in CR animals. A prominent role for triokinase in glyceraldehyde metabolism with CR was also observed. The results indicate that long-term CR induces sustained increases in the capacity for gluconeogenesis from glycerol. PMID:18429748

  12. Restoration of physical performance capacity of athletes after prolonged restriction of their motor activity

    NASA Technical Reports Server (NTRS)

    Soldatov, A. D.; Finogeyev, V. I.

    1980-01-01

    The effects of different regimens of treatment following prolonged hypokinesia were studied in order to determine the most effective program. The types of programs considered were passive means, consisting of physical therapy; active means, consisting of athletic training; and a combined program. In the first stage of the experiment, the effects of a 10 day period of hypokinesia were studied. It was determined that the restoration programs must address the problems of: (1) increasing defense function and general tone of the body; (2) restore orthostatic stability; and (3) increase general endurance. In later stages, groups of athletes and nonathletes underwent 30 day periods of hypokinesia. Restoration was carefully monitored for groups treated with the various regimens. It was determined that the most effective treatment was a comprehensive program of passive and active therapy.

  13. GTP activator and dNTP substrates of HIV-1 restriction factor SAMHD1 generate a long-lived activated state

    PubMed Central

    Hansen, Erik C.; Seamon, Kyle J.; Cravens, Shannen L.; Stivers, James T.

    2014-01-01

    The HIV-1 restriction factor sterile α-motif/histidine-aspartate domain-containing protein 1 (SAMHD1) is a tetrameric protein that catalyzes the hydrolysis of all dNTPs to the deoxynucleoside and tripolyphosphate, which effectively depletes the dNTP substrates of HIV reverse transcriptase. Here, we establish that SAMHD1 is activated by GTP binding to guanine-specific activator sites (A1) as well as coactivation by substrate dNTP binding to a distinct set of nonspecific activator sites (A2). Combined activation by GTP and dNTPs results in a long-lived tetrameric form of SAMHD1 that persists for hours, even after activating nucleotides are withdrawn from the solution. These results reveal an ordered model for assembly of SAMHD1 tetramer from its inactive monomer and dimer forms, where GTP binding to the A1 sites generates dimer and dNTP binding to the A2 and catalytic sites generates active tetramer. Thus, cellular regulation of active SAMHD1 is not determined by GTP alone but instead, the levels of all dNTPs and the generation of a persistent tetramer that is not in equilibrium with free activators. The significance of the long-lived activated state is that SAMHD1 can remain active long after dNTP pools have been reduced to a level that would lead to inactivation. This property would be important in resting CD4+ T cells, where dNTP pools are reduced to nanomolar levels to restrict infection by HIV-1. PMID:24753578

  14. Cardiac Glycosides Activate the Tumor Suppressor and Viral Restriction Factor Promyelocytic Leukemia Protein (PML)

    PubMed Central

    Milutinovic, Snezana; Heynen-Genel, Susanne; Chao, Elizabeth; Dewing, Antimone; Solano, Ricardo; Milan, Loribelle; Barron, Nikki; He, Min; Diaz, Paul W.; Matsuzawa, Shu-ichi; Reed, John C.; Hassig, Christian A.

    2016-01-01

    Cardiac glycosides (CGs), inhibitors of Na+/K+-ATPase (NKA), used clinically to treat heart failure, have garnered recent attention as potential anti-cancer and anti-viral agents. A high-throughput phenotypic screen designed to identify modulators of promyelocytic leukemia protein (PML) nuclear body (NB) formation revealed the CG gitoxigenin as a potent activator of PML. We demonstrate that multiple structurally distinct CGs activate the formation of PML NBs and induce PML protein SUMOylation in an NKA-dependent fashion. CG effects on PML occur at the post-transcriptional level, mechanistically distinct from previously described PML activators and are mediated through signaling events downstream of NKA. Curiously, genomic deletion of PML in human cancer cells failed to abrogate the cytotoxic effects of CGs and other apoptotic stimuli such as ceramide and arsenic trioxide that were previously shown to function through PML in mice. These findings suggest that alternative pathways can compensate for PML loss to mediate apoptosis in response to CGs and other apoptotic stimuli. PMID:27031987

  15. Cardiac Glycosides Activate the Tumor Suppressor and Viral Restriction Factor Promyelocytic Leukemia Protein (PML).

    PubMed

    Milutinovic, Snezana; Heynen-Genel, Susanne; Chao, Elizabeth; Dewing, Antimone; Solano, Ricardo; Milan, Loribelle; Barron, Nikki; He, Min; Diaz, Paul W; Matsuzawa, Shu-ichi; Reed, John C; Hassig, Christian A

    2016-01-01

    Cardiac glycosides (CGs), inhibitors of Na+/K+-ATPase (NKA), used clinically to treat heart failure, have garnered recent attention as potential anti-cancer and anti-viral agents. A high-throughput phenotypic screen designed to identify modulators of promyelocytic leukemia protein (PML) nuclear body (NB) formation revealed the CG gitoxigenin as a potent activator of PML. We demonstrate that multiple structurally distinct CGs activate the formation of PML NBs and induce PML protein SUMOylation in an NKA-dependent fashion. CG effects on PML occur at the post-transcriptional level, mechanistically distinct from previously described PML activators and are mediated through signaling events downstream of NKA. Curiously, genomic deletion of PML in human cancer cells failed to abrogate the cytotoxic effects of CGs and other apoptotic stimuli such as ceramide and arsenic trioxide that were previously shown to function through PML in mice. These findings suggest that alternative pathways can compensate for PML loss to mediate apoptosis in response to CGs and other apoptotic stimuli. PMID:27031987

  16. Restriction of Replication Fork Regression Activities by a Conserved SMC Complex

    PubMed Central

    Xue, Xiaoyu; Choi, Koyi; Bonner, Jaclyn; Chiba, Tamara; Kwon, Youngho; Xu, Yuanyuan; Sanchez, Humberto; Wyman, Claire; Niu, Hengyao; Zhao, Xiaolan; Sung, Patrick

    2014-01-01

    SUMMARY Conserved, multi-tasking DNA helicases mediate diverse DNA transactions and are relevant for human disease pathogenesis. These helicases and their regulation help maintain genome stability during DNA replication and repair. We show that the structural maintenance of chromosome complex Smc5-Smc6 restrains the replication fork regression activity of Mph1 helicase, but not its D-loop disruptive activity. This regulatory mechanism enables flexibility in replication fork repair without interfering with DNA break repair. In vitro studies find that Smc5-Smc6 binds to a Mph1 region required for efficient fork regression, preventing assembly of Mph1 oligomers at the junction of DNA forks. In vivo impairment of this regulatory mechanism compensates for the inactivation of another fork regression helicase and increases reliance on joint DNA structure removal or avoidance. Our findings provide molecular insights into replication fork repair regulation and uncover a role of Smc5-Smc6 in directing Mph1 activity towards a specific biochemical outcome. PMID:25439736

  17. Multi-scale statistical analysis of coronal solar activity

    DOE PAGESBeta

    Gamborino, Diana; del-Castillo-Negrete, Diego; Martinell, Julio J.

    2016-07-08

    Multi-filter images from the solar corona are used to obtain temperature maps that are analyzed using techniques based on proper orthogonal decomposition (POD) in order to extract dynamical and structural information at various scales. Exploring active regions before and after a solar flare and comparing them with quiet regions, we show that the multi-scale behavior presents distinct statistical properties for each case that can be used to characterize the level of activity in a region. Information about the nature of heat transport is also to be extracted from the analysis.

  18. Multi-scale statistical analysis of coronal solar activity

    NASA Astrophysics Data System (ADS)

    Gamborino, Diana; del-Castillo-Negrete, Diego; Martinell, Julio J.

    2016-07-01

    Multi-filter images from the solar corona are used to obtain temperature maps that are analyzed using techniques based on proper orthogonal decomposition (POD) in order to extract dynamical and structural information at various scales. Exploring active regions before and after a solar flare and comparing them with quiet regions, we show that the multi-scale behavior presents distinct statistical properties for each case that can be used to characterize the level of activity in a region. Information about the nature of heat transport is also to be extracted from the analysis.

  19. A restricted parabrachial pontine region is active during non-REM sleep

    PubMed Central

    Torterolo, Pablo; Sampogna, Sharon; Chase, Michael H.

    2011-01-01

    The principal site that generates both REM sleep and wakefulness is located in the mesopontine reticular formation, whereas non-REM sleep (NREM) is primarily dependent upon the functioning of neurons that are located in the preoptic region of the hypothalamus. In the present study, we were interested in determining whether the occurrence of NREM might also depend on the activity of mesopontine structures, as has been shown for wakefulness and REM sleep. Adult cats were maintained in one of the following states: quiet wakefulness (QW), alert wakefulness (AW), NREM, or REM sleep induced by microinjections of carbachol into the nucleus pontis oralis (REM-carbachol). Subsequently, they were euthanized and single labeling immunohistochemical studies were undertaken to determine state-dependent patterns of neuronal activity in the brainstem based upon the expression of the protein Fos. In addition, double labeling immunohistochemical studies were carried out to detect neurons that expressed Fos as well as choline acetyltransferase, tyrosine hydroxylase or GABA. During NREM, only a few Fos immunoreactive cells were present in different regions of the brainstem; however, a discrete cluster of Fos+ neurons was observed in the caudolateral peribrachial region (CLPB). The number of the Fos+ neurons in the CLPB during NREM was significantly greater (67.9 ± 10.9, P < 0.0001) compared to QW (8.0 ± 6.7), AW (5.2 ± 4.2) or REM-carbachol (8.0 ± 4.7). In addition, there was a positive correlation (R = 0.93) between the time the animals spent in NREM and the number of Fos+ neurons in the CLPB. Fos-immunoreactive neurons in the CLPB were neither cholinergic nor catecholaminergic; however about 50% of these neurons were GABAergic. We conclude that a group of GABAergic and unidentified neurons in the CLPB are active during NREM and likely involved in the control of this behavioral state. These data open new avenues for the study of NREM, as well as for the explorations of

  20. A spectroscopic method to determine the activity of the restriction endonuclease EcoRV that involves a single reaction.

    PubMed

    Huang, Qing; Quiñones, Edwin

    2016-03-15

    A one-step protocol is presented to determine the activity of EcoRV as a model of restriction enzymes. The protocol involved a molecular beacon as DNA substrate, with the target sequence recognized by EcoRV in the stem. EcoRV cleaved the stem forming two fragments, one of which contained the fluorophore and quencher, initially bound by 3 bp. This shorter fragment rapidly dissociated at 37 °C, causing an increase of fluorescence intensity that was used to gauge the reaction kinetics. The reaction can be described using the Michaelis-Menten mechanism, and the kinetic parameters obtained were compared with literature values involving other protocols. PMID:18489897

  1. Second-order perturbative corrections to the restricted active space configuration interaction with the hole and particle approach

    NASA Astrophysics Data System (ADS)

    Casanova, David

    2014-04-01

    Second-order corrections to the restricted active space configuration interaction (RASCI) with the hole and particle truncation of the excitation operator are developed. Theoretically, the computational cost of the implemented perturbative approach, abbreviated as RASCI(2), grows like its single reference counterpart in MP2. Two different forms of RASCI(2) have been explored, that is the generalized Davidson-Kapuy and the Epstein-Nesbet partitions of the Hamiltonian. The preliminary results indicate that the use of energy level shift of a few tenths of a Hartree might systematically improve the accuracy of the RASCI(2) energies. The method has been tested in the computation of the ground state energy profiles along the dissociation of the hydrogen fluoride and N2 molecules, the computation of correlation energy in the G2/97 molecular test set, and in the computation of excitation energies to low-lying states in small organic molecules.

  2. Second-order perturbative corrections to the restricted active space configuration interaction with the hole and particle approach

    SciTech Connect

    Casanova, David

    2014-04-14

    Second-order corrections to the restricted active space configuration interaction (RASCI) with the hole and particle truncation of the excitation operator are developed. Theoretically, the computational cost of the implemented perturbative approach, abbreviated as RASCI(2), grows like its single reference counterpart in MP2. Two different forms of RASCI(2) have been explored, that is the generalized Davidson-Kapuy and the Epstein-Nesbet partitions of the Hamiltonian. The preliminary results indicate that the use of energy level shift of a few tenths of a Hartree might systematically improve the accuracy of the RASCI(2) energies. The method has been tested in the computation of the ground state energy profiles along the dissociation of the hydrogen fluoride and N{sub 2} molecules, the computation of correlation energy in the G2/97 molecular test set, and in the computation of excitation energies to low-lying states in small organic molecules.

  3. Scale Development for Perceived School Climate for Girls’ Physical Activity

    PubMed Central

    Birnbaum, Amanda S.; Evenson, Kelly R.; Motl, Robert W.; Dishman, Rod K.; Voorhees, Carolyn C.; Sallis, James F.; Elder, John P.; Dowda, Marsha

    2008-01-01

    Objectives To test an original scale assessing perceived school climate for girls’ physical activity in middle school girls. Methods Confirmatory factor analysis (CFA) and structural equation modeling (SEM). Results CFA retained 5 of 14 original items. A model with 2 correlated factors, perceptions about teachers’ and boys’ behaviors, respectively, fit the data well in both sixth and eighth graders. SEM detected a positive, significant direct association of the teacher factor, but not the boy factor, with girls’ self-reported physical activity. Conclusions School climate for girls’ physical activity is a measurable construct, and preliminary evidence suggests a relationship with physical activity. PMID:15899688

  4. Conserved Overlapping Gene Arrangement, Restricted Expression, and Biochemical Activities of DNA Polymerase ν (POLN)*

    PubMed Central

    Takata, Kei-ichi; Tomida, Junya; Reh, Shelley; Swanhart, Lisa M.; Takata, Minoru; Hukriede, Neil A.; Wood, Richard D.

    2015-01-01

    DNA polymerase ν (POLN) is one of 16 DNA polymerases encoded in vertebrate genomes. It is important to determine its gene expression patterns, biological roles, and biochemical activities. By quantitative analysis of mRNA expression, we found that POLN from the zebrafish Danio rerio is expressed predominantly in testis. POLN is not detectably expressed in zebrafish embryos or in mouse embryonic stem cells. Consistent with this, injection of POLN-specific morpholino antisense oligonucleotides did not interfere with zebrafish embryonic development. Analysis of transcripts revealed that vertebrate POLN has an unusual gene expression arrangement, sharing a first exon with HAUS3, the gene encoding augmin-like complex subunit 3. HAUS3 is broadly expressed in embryonic and adult tissues, in contrast to POLN. Differential expression of POLN and HAUS3 appears to arise by alternate splicing of transcripts in mammalian cells and zebrafish. When POLN was ectopically overexpressed in human cells, it specifically coimmunoprecipitated with the homologous recombination factors BRCA1 and FANCJ, but not with previously suggested interaction partners (HELQ and members of the Fanconi anemia core complex). Purified zebrafish POLN protein is capable of thymine glycol bypass and strand displacement, with activity dependent on a basic amino acid residue known to stabilize the primer-template. These properties are conserved with the human enzyme. Although the physiological function of pol ν remains to be clarified, this study uncovers distinctive aspects of its expression control and evolutionarily conserved properties of this DNA polymerase. PMID:26269593

  5. Adipose tissue and vascular phenotypic modulation by voluntary physical activity and dietary restriction in obese insulin-resistant OLETF rats

    PubMed Central

    Crissey, Jacqueline M.; Jenkins, Nathan T.; Lansford, Kasey A.; Thorne, Pamela K.; Bayless, David S.; Vieira-Potter, Victoria J.; Rector, R. Scott; Thyfault, John P.; Laughlin, M. Harold

    2014-01-01

    Adipose tissue (AT)-derived cytokines are proposed to contribute to obesity-associated vascular insulin resistance. We tested the hypothesis that voluntary physical activity and diet restriction-induced maintenance of body weight would both result in decreased AT inflammation and concomitant improvements in insulin-stimulated vascular relaxation in the hyperphagic, obese Otsuka Long-Evans Tokushima fatty (OLETF) rat. Rats (aged 12 wk) were randomly assigned to sedentary (SED; n = 10), wheel running (WR; n = 10), or diet restriction (DR; n = 10; fed 70% of SED) for 8 wk. WR and DR rats exhibited markedly lower adiposity (7.1 ± 0.4 and 15.7 ± 1.1% body fat, respectively) relative to SED (27 ± 1.2% body fat), as well as improved blood lipid profiles and systemic markers of insulin resistance. Reduced adiposity in both WR and DR was associated with decreased AT mRNA expression of inflammatory genes (e.g., MCP-1, TNF-α, and IL-6) and markers of immune cell infiltration (e.g., CD8, CD11c, and F4/80). The extent of these effects were most pronounced in visceral AT compared with subcutaneous and periaortic AT. Markers of inflammation in brown AT were upregulated with WR but not DR. In periaortic AT, WR- and DR-induced reductions in expression and secretion of cytokines were accompanied with a more atheroprotective gene expression profile in the adjacent aortic wall. WR, but not DR, resulted in greater insulin-stimulated relaxation in the aorta; an effect that was, in part, mediated by a decrease in insulin-induced endothelin-1 activation in WR aorta. Collectively, we show in OLETF rats that lower adiposity leads to less AT and aortic inflammation, as well as an exercise-specific improvement in insulin-stimulated vasorelaxation. PMID:24523340

  6. Stringent restriction from the growth of large-scale structure on apparent acceleration in inhomogeneous cosmological models.

    PubMed

    Ishak, Mustapha; Peel, Austin; Troxel, M A

    2013-12-20

    Probes of cosmic expansion constitute the main basis for arguments to support or refute a possible apparent acceleration due to different expansion rates in the Universe as described by inhomogeneous cosmological models. We present in this Letter a separate argument based on results from an analysis of the growth rate of large-scale structure in the Universe as modeled by the inhomogeneous cosmological models of Szekeres. We use the models with no assumptions of spherical or axial symmetries. We find that while the Szekeres models can fit very well the observed expansion history without a Λ, they fail to produce the observed late-time suppression in the growth unless Λ is added to the dynamics. A simultaneous fit to the supernova and growth factor data shows that the cold dark matter model with a cosmological constant (ΛCDM) provides consistency with the data at a confidence level of 99.65%, while the Szekeres model without Λ achieves only a 60.46% level. When the data sets are considered separately, the Szekeres with no Λ fits the supernova data as well as the ΛCDM does, but provides a very poor fit to the growth data with only 31.31% consistency level compared to 99.99% for the ΛCDM. This absence of late-time growth suppression in inhomogeneous models without a Λ is consolidated by a physical explanation. PMID:24483736

  7. Conformational Restriction Leading to a Selective CB2 Cannabinoid Receptor Agonist Orally Active Against Colitis

    PubMed Central

    2014-01-01

    The CB2 cannabinoid receptor has been implicated in the regulation of intestinal inflammation. Following on from the promising activity of a series of 4-oxo-1,4-dihydroquinoline-3-carboxamide, we developed constrained analogues based on a 2H-pyrazolo[4,3-c]quinolin-3(5H)-one scaffold, with improved affinity for the hCB2 receptor and had very high selectivity over the hCB1 receptor. Importantly, the lead of this series (26, hCB2: Ki = 0.39 nM, hCB1: Ki > 3000 nM) was found to protect mice against experimental colitis after oral administration. PMID:25699149

  8. Human-restricted bacterial pathogens block shedding of epithelial cells by stimulating integrin activation.

    PubMed

    Muenzner, Petra; Bachmann, Verena; Zimmermann, Wolfgang; Hentschel, Jochen; Hauck, Christof R

    2010-09-01

    Colonization of mucosal surfaces is the key initial step in most bacterial infections. One mechanism protecting the mucosa is the rapid shedding of epithelial cells, also termed exfoliation, but it is unclear how pathogens counteract this process. We found that carcinoembryonic antigen (CEA)-binding bacteria colonized the urogenital tract of CEA transgenic mice, but not of wild-type mice, by suppressing exfoliation of mucosal cells. CEA binding triggered de novo expression of the transforming growth factor receptor CD105, changing focal adhesion composition and activating beta1 integrins. This manipulation of integrin inside-out signaling promotes efficient mucosal colonization and represents a potential target to prevent or cure bacterial infections. PMID:20813953

  9. Basic properties of magnetic flux tubes and restrictions on theories of solar activity

    NASA Technical Reports Server (NTRS)

    Parker, E. N.

    1976-01-01

    It is shown that the mean longitudinal field in a magnetic flux tube is reduced, rather than enhanced, by twisting the tube to form a rope. It is shown that there is no magnetohydrostatic equilibrium when one twisted rope is wound around another. Instead there is rapid line cutting (neutral point annihilation). It is shown that the twisting increases, and the field strength decreases, along a flux tube extending upward through a stratified atmosphere. These facts are at variance with Piddington's (1975) recent suggestion that solar activity is to be understood as the result of flux tubes which are enormously concentrated by twisting, which consist of several twisted ropes wound around each other, and which came untwisted where they emerge through the photosphere.

  10. Restricted Heterochromatin Formation Links NFATc2 Repressor Activity With Growth Promotion in Pancreatic Cancer

    PubMed Central

    BAUMGART, SANDRA; GLESEL, ELISABETH; SINGH, GARIMA; CHEN, NAI-MING; REUTLINGER, KRISTINA; ZHANG, JINSAN; BILLADEAU, DANIEL D.; FERNANDEZ-ZAPICO, MARTIN E.; GRESS, THOMAS M.; SINGH, SHIV K.; ELLENRIEDER, VOLKER

    2012-01-01

    BACKGROUND & AIMS Transcriptional silencing of the p15INK4b tumor suppressor pathway overcomes cellular protection against unrestrained proliferation in cancer. Here we show a novel pathway involving the oncogenic transcription factor nuclear factor of activated T cells (NFAT) c2 targeting a p15INK4b-mediated failsafe mechanism to promote pancreatic cancer tumor growth. METHODS Immunohistochemistry, real-time polymerase chain reaction, immunoblotting, and immunofluorescence microscopy were used for expression studies. Cancer growth was assessed in vitro by [3H]thymidine incorporation, colony formation assays, and in vivo using xenograft tumor models. Protein-protein interactions, promoter regulation, and local histone modifications were analyzed by immunoprecipitation, DNA pull-down, reporter, and chromatin immunoprecipitation assays. RESULTS Our study uncovered induction of NFATc2 in late-stage pancreatic intraepithelial neoplasia lesions with increased expression in tumor cell nuclei of advanced cancers. In the nucleus, NFATc2 targets the p15INK4b promoter for inducible heterochromatin formation and silencing. NFATc2 binding to its cognate promoter site induces stepwise recruitment of the histone methyltransferase Suv39H1, causes local H3K9 trimethylation, and allows docking of heterochromatin protein HP1γ to the repressor complex. Conversely, inactivation of NFATc2 disrupts this repressor complex assembly and local heterochromatin formation, resulting in restoration of p15INK4b expression and inhibition of pancreatic cancer growth in vitro and in vivo. CONCLUSIONS Here we describe a novel mechanism for NFATc2-mediated gene regulation and identify a functional link among its repressor activity, the silencing of the suppressor pathway p15INK4b, and its pancreatic cancer growth regulatory functions. Thus, we provide evidence that inactivation of oncogenic NFATc2 might be an attractive strategy in treatment of pancreatic cancer. PMID:22079596

  11. Prolactin prevents hepatocellular carcinoma by restricting innate immune activation of c-Myc in mice.

    PubMed

    Hartwell, Hadley J; Petrosky, Keiko Y; Fox, James G; Horseman, Nelson D; Rogers, Arlin B

    2014-08-01

    Women are more resistant to hepatocellular carcinoma (HCC) than men despite equal exposure to major risk factors, such as hepatitis B or C virus infection. Female resistance is hormone-dependent, as evidenced by the sharp increase in HCC incidence in postmenopausal women who do not take hormone replacement therapy. In rodent models sex-dimorphic HCC phenotypes are pituitary-dependent, suggesting that sex hormones act via the gonadal-hypophyseal axis. We found that the estrogen-responsive pituitary hormone prolactin (PRL), signaling through hepatocyte-predominant short-form prolactin receptors (PRLR-S), constrained TNF receptor-associated factor (TRAF)-dependent innate immune responses invoked by IL-1β, TNF-α, and LPS/Toll-like receptor 4 (TLR4), but not TRIF-dependent poly(I:C)/TLR3. PRL ubiquitinated and accelerated poststimulatory decay of a "trafasome" comprised of IRAK1, TRAF6, and MAP3K proteins, abrogating downstream activation of c-Myc-interacting pathways, including PI3K/AKT, mTORC1, p38 MAPK, and NF-κB. Consistent with this finding, we documented exaggerated male liver responses to immune stimuli in mice and humans. Tumor promotion through, but regulation above, the level of c-Myc was demonstrated by sex-independent HCC eruption in Alb-Myc transgenic mice. PRL deficiency accelerated liver carcinogenesis in Prl(-/-) mice of both sexes. Conversely, pharmacologic PRL mobilization using the dopamine D2 receptor antagonist domperidone prevented HCC in tumor-prone C3H/HeN males. Viewed together, our results demonstrate that PRL constrains tumor-promoting liver inflammation by inhibiting MAP3K-dependent activation of c-Myc at the level of the trafasome. PRL-targeted therapy may hold promise for reducing the burden of liver cancer in high-risk men and women. PMID:25049387

  12. Solar Irradiance Variations on Active Region Time Scales

    NASA Technical Reports Server (NTRS)

    Labonte, B. J. (Editor); Chapman, G. A. (Editor); Hudson, H. S. (Editor); Willson, R. C. (Editor)

    1984-01-01

    The variations of the total solar irradiance is an important tool for studying the Sun, thanks to the development of very precise sensors such as the ACRIM instrument on board the Solar Maximum Mission. The largest variations of the total irradiance occur on time scales of a few days are caused by solar active regions, especially sunspots. Efforts were made to describe the active region effects on total and spectral irradiance.

  13. Food restriction and spontaneous motor activity in male mice: effects of feeding pattern, far-infrared ray and bamboo grass leaf extract.

    PubMed

    Nagasawa, H; Murayama, Y; Ishigame, H

    2001-01-01

    The effects on spontaneous motor activity of the pattern of restricted feeding, far-infrared ray (FIR) irradiation or free access in drinking water containing Sasa Health, a bamboo grass leafextract, were examined in SHN male mice at 2-3 months of age. In mice whose diet was restricted to 60% of the control, fed at 9:00 or 17:00 hours, the level of spontaneous behaviour was elevated 1 hour before the respective feeding time (8:00 or 16:00 hours). The activity was stimulated by FIR in both the control and food-restricted mice, but to a much higher degree in the latter. Treatment with Sasa Health in drinking water lowered the elevated activity level in food-restricted mice. Plasma component levels and organ weights were modulated by FIR or Sasa Health. The findings revealed that, not only the restricted feeding itsel, but also its pattern, significantly affected behaviour and that FIR and Sasa Health modified the deleterious effects of restricted feeding. PMID:11695223

  14. SciDAC Institute for Ultra-Scale Visualization: Activity Recognition for Ultra-Scale Visualization

    SciTech Connect

    Silver, Deborah

    2014-04-30

    Understanding the science behind ultra-scale simulations requires extracting meaning from data sets of hundreds of terabytes or more. Developing scalable parallel visualization algorithms is a key step enabling scientists to interact and visualize their data at this scale. However, at extreme scales, the datasets are so huge, there is not even enough time to view the data, let alone explore it with basic visualization methods. Automated tools are necessary for knowledge discovery -- to help sift through the information and isolate characteristic patterns, thereby enabling the scientist to study local interactions, the origin of features and their evolution in large volumes of data. These tools must be able to operate on data of this scale and work with the visualization process. In this project, we developed a framework for activity detection to allow scientists to model and extract spatio-temporal patterns from time-varying data.

  15. Development of the Faith Activities in the Home Scale (FAITHS)

    ERIC Educational Resources Information Center

    Lambert, Nathaniel M.; Dollahite, David C.

    2010-01-01

    This article reports the development of the Faith Activities In The Home Scale (FAITHS). The initial FAITHS measure was improved on and expanded by using qualitative data of two separate samples and then empirically tested on three separate samples. Study 1 comprised two samples totaling 57 highly religious families from New England and California…

  16. Scale Development for Perceived School Climate for Girls' Physical Activity

    ERIC Educational Resources Information Center

    Birnbaum, Amanda S.; Evenson, Kelly R.; Motl, Robert W.; Dishman, Rod K.; Voorhees, Carolyn C.; Sallis, James F.; Elder, John P.; Dowda, Marsha

    2005-01-01

    Objectives: To test an original scale assessing perceived school climate for girls' physical activity in middle school girls. Methods: Confirmatory factor analysis (CFA) and structural equation modeling (SEM). Results: CFA retained 5 of 14 original items. A model with 2 correlated factors, perceptions about teachers' and boys' behaviors,…

  17. Restrictive cardiomyopathy

    MedlinePlus

    ... blood returns from the body (diastole). When the disease progresses, the heart may not pump blood strongly. The abnormal heart function can affect the lungs, liver, and other body systems. Restrictive cardiomyopathy may affect either or both of the ...

  18. Restrictive cardiomyopathy

    MedlinePlus

    ... blood returns from the body (diastole). When the disease progresses, the heart may not pump blood strongly. The abnormal heart function can affect the lungs, liver, and other body systems. Restrictive cardiomyopathy may affect ...

  19. Anatomically restricted synergistic anti-viral activities of innate and adaptive immune cells in the skin

    PubMed Central

    Hickman, Heather D.; Reynoso, Glennys V.; Ngudiankama, Barbara F.; Rubin, Erica J.; Magadán, Javier G.; Cush, Stephanie S.; Gibbs, James; Molon, Barbara; Bronte, Vincenzo; Bennink, Jack R.; Yewdell, Jonathan W.

    2013-01-01

    SUMMARY Despite extensive ex vivo investigation, the spatiotemporal organization of immune cells interacting with virus-infected cells in tissues remains uncertain. To address this, we used intravital multiphoton microscopy to visualize immune cell interactions with virus-infected cells following epicutaneous vaccinia virus (VV) infection of mice. VV infects keratinocytes in epidermal foci, and numerous migratory dermal inflammatory monocytes outlying the foci. We observed Ly6G+ innate immune cells infiltrating and controlling foci, while CD8+ T cells remained on the periphery killing infected monocytes. Most antigen-specific CD8+ T cells in the skin did not interact with virus-infected cells. Blocking the generation of reactive nitrogen species relocated CD8+ T cells into foci, modestly reducing viral titers. Depletion of Ly6G+ and CD8+ cells dramatically increased viral titers, consistent with their synergistic but spatially segregated viral clearance activities. These findings highlight previously unappreciated differences in the anatomic specialization of antiviral immune cell subsets. PMID:23414756

  20. Calorie restriction leads to greater Akt2 activity and glucose uptake by insulin-stimulated skeletal muscle from old rats.

    PubMed

    Wang, Haiyan; Arias, Edward B; Cartee, Gregory D

    2016-03-01

    Skeletal muscle insulin resistance is associated with many common age-related diseases, but moderate calorie restriction (CR) can substantially elevate glucose uptake by insulin-stimulated skeletal muscle from both young and old rats. The current study evaluated the isolated epitrochlearis muscle from ∼24.5-mo-old rats that were either fed ad libitum (AL) or subjected to CR (consuming ∼65% of ad libitum, AL, intake beginning at ∼22.5 mo old). Some muscles were also incubated with MK-2206, a potent and selective Akt inhibitor. The most important results were that in isolated muscles, CR vs. AL resulted in 1) greater insulin-stimulated glucose uptake 2) that was accompanied by significantly increased insulin-mediated activation of Akt2, as indicated by greater phosphorylation on both Thr(309) and Ser(474) along with greater Akt2 activity, 3) concomitant with enhanced phosphorylation of several Akt substrates, including an Akt substrate of 160 kDa on Thr(642) and Ser(588), filamin C on Ser(2213) and proline-rich Akt substrate of 40 kDa on Thr(246), but not TBC1D1 on Thr(596); and 4) each of the CR effects was eliminated by MK-2206. These data provide compelling new evidence linking greater Akt2 activation to the CR-induced elevation of insulin-stimulated glucose uptake by muscle from old animals. PMID:26739650

  1. Effect of calorie restriction on spontaneous physical activity and body mass in mice divergently selected for basal metabolic rate (BMR).

    PubMed

    Brzęk, Paweł; Gębczyński, Andrzej K; Książek, Aneta; Konarzewski, Marek

    2016-07-01

    Spontaneous physical activity (SPA) represents an important component of daily energy expenditures in animals and humans. Intra-specific variation in SPA may be related to the susceptibility to metabolic disease or obesity. In particular, reduced SPA under conditions of limited food availability may conserve energy and prevent loss of body and fat mass ('thrifty genotype hypothesis'). However, both SPA and its changes during food restriction show wide inter-individual variations. We studied the effect of 30% caloric restriction (CR) on SPA in laboratory mice divergently selected for high (H-BMR) and low (L-BMR) basal metabolic rate. Selection increased SPA in the H-BMR line but did not change it in the L-BMR mice. This effect reflected changes in SPA intensity but not SPA duration. CR increased SPA intensity more strongly in the L-BMR line than in the H-BMR line and significantly modified the temporal variation of SPA. However, the initial between-line differences in SPA were not affected by CR. Loss of body mass during CR did not differ between both lines. Our results show that the H-BMR mice can maintain their genetically determined high SPA under conditions of reduced food intake without sacrificing their body mass. We hypothesize that this pattern may reflect the higher flexibility in the energy budget in the H-BMR line, as we showed previously that mice from this line reduced their BMR during CR. These energy savings may allow for the maintenance of elevated SPA in spite of reduced food intake. We conclude that the effect of CR on SPA is in large part determined by the initial level of BMR, whose variation may account for the lack of universal pattern of behavioural responses to CR. PMID:27090226

  2. MHC-I non-restricted cytotoxic activity in Macaca sylvana experimentally inoculated with HIV2 and SIV/mac.

    PubMed

    Charaf, B; Sanhadji, K; Sekkat, S; Farouqui, B; Touraine, J L; Benslimane, A

    1993-08-01

    The anti-retrovirus cell-mediated immunity was repeatedly investigated in seven monkeys (Macaca sylvana). Four of these animals were injected with cell-free supernatants containing human immunodeficiency viruses: two monkeys received HIV1 Bru (2.5 x 10(6) cpm), two received HIV2 Rod (1.5 x 10(6) cpm). Two additional animals were injected with a cell-free supernatant containing simian immunodeficiency virus SIV/mac 251 (1.5 x 10(6) cpm) and the last animal served as control. The four macaques infected with HIV2 Rod and SIV/mac 251 seroconverted. Freshly isolated and non stimulated peripheral blood mononuclear cells from these infected macaques and from the uninfected control were repeatedly assessed for cytolytic activity. Target cells consisted of heterologous human cell lines expressing HIV1 Bru, HIV2 Rod or SIV/mac proteins. A significant cytotoxic activity, non-restricted at the major histocompatibility complex class I (MHC-I), was demonstrated in one HIV2 Rod-infected animal (F8) and in one SIV/mac 251-infected animal (M1). This last animal showed progressively diminishing cytolytic activity that was correlated with a pronounced decrease in CD4+ lymphocytes. An AIDS-like disease developed in M1, with presence of lymphadenopathy, weight loss, diarrhea and opportunistic infections. Cytotoxic activity was active against SIV and HIV2-infected target cells in an MHC-unrestricted manner; it was specific to virus-infected cells and there was cross-reactivity between HIV2 and SIV. Cytotoxic effectors appeared to be mainly CD8+ cells. This model may prove to be very useful in evaluating the capacity of candidate AIDS vaccines to elicit effective cell-mediated immune responses. PMID:7905683

  3. The retinal determination gene Dachshund restricts cell proliferation by limiting the activity of the Homothorax-Yorkie complex.

    PubMed

    Brás-Pereira, Catarina; Casares, Fernando; Janody, Florence

    2015-04-15

    The Drosophila transcriptional co-activator protein Yorkie and its vertebrate orthologs YAP and TAZ are potent oncogenes, whose activity is normally kept in check by the upstream Hippo kinase module. Upon its translocation into the nucleus, Yorkie forms complexes with several tissue-specific DNA-binding partners, which help to define the tissue-specific target genes of Yorkie. In the progenitor cells of the eye imaginal disc, the DNA-binding transcription factor Homothorax is required for Yorkie-promoted proliferation and survival through regulation of the bantam microRNA (miRNA). The transit from proliferating progenitors to cell cycle quiescent precursors is associated with the progressive loss of Homothorax and gain of Dachshund, a nuclear protein related to the Sno/Ski family of co-repressors. We have identified Dachshund as an inhibitor of Homothorax-Yorkie-mediated cell proliferation. Loss of dachshund induces Yorkie-dependent tissue overgrowth. Conversely, overexpressing dachshund inhibits tissue growth, prevents Yorkie or Homothorax-mediated cell proliferation of disc epithelia and restricts the transcriptional activity of the Yorkie-Homothorax complex on the bantam enhancer in Drosophila cells. In addition, Dachshund collaborates with the Decapentaplegic receptor Thickveins to repress Homothorax and Cyclin B expression in quiescent precursors. The antagonistic roles of Homothorax and Dachshund in Yorkie activity, together with their mutual repression, ensure that progenitor and precursor cells are under distinct proliferation regimes. Based on the crucial role of the human dachshund homolog DACH1 in tumorigenesis, our work suggests that DACH1 might prevent cellular transformation by limiting the oncogenic activity of YAP and/or TAZ. PMID:25790852

  4. n-back task performance and corresponding brain-activation patterns in women with restrictive and bulimic eating-disorder variants: preliminary findings.

    PubMed

    Israel, Mimi; Klein, Michael; Pruessner, Jens; Thaler, Lea; Spilka, Michael; Efanov, Simona; Ouellette, Anne-Sophie; Berlim, Marcelo; Ali, Nida; Beaudry, Thomas; Van den Eynde, Frederique; Walker, Claire-Dominique; Steiger, Howard

    2015-04-30

    Eating disorder (ED) variants characterized by "binge-eating/purging" symptoms differ from "restricting-only" variants along diverse clinical dimensions, but few studies have compared people with these different eating-disorder phenotypes on measures of neurocognitive function and brain activation. We tested the performances of 19 women with "restricting-only" eating syndromes and 27 with "binge-eating/purging" variants on a modified n-back task, and used functional magnetic resonance imaging (fMRI) to examine task-induced brain activations in frontal regions of interest. When compared with "binge-eating/purging" participants, "restricting-only" participants showed superior performance. Furthermore, in an intermediate-demand condition, "binge-eating/purging" participants showed significantly less event-related activation than did "restricting-only" participants in a right posterior prefrontal region spanning Brodmann areas 6-8-a region that has been linked to planning of motor responses, working memory for sequential information, and management of uncertainty. Our findings suggest that working memory is poorer in eating-disordered individuals with binge-eating/purging behaviors than in those who solely restrict food intake, and that observed performance differences coincide with interpretable group-based activation differences in a frontal region thought to subserve planning and decision making. PMID:25707581

  5. Cost and sensitivity of restricted active-space calculations of metal L-edge X-ray absorption spectra.

    PubMed

    Pinjari, Rahul V; Delcey, Mickaël G; Guo, Meiyuan; Odelius, Michael; Lundberg, Marcus

    2016-02-15

    The restricted active-space (RAS) approach can accurately simulate metal L-edge X-ray absorption spectra of first-row transition metal complexes without the use of any fitting parameters. These characteristics provide a unique capability to identify unknown chemical species and to analyze their electronic structure. To find the best balance between cost and accuracy, the sensitivity of the simulated spectra with respect to the method variables has been tested for two models, [FeCl6 ](3-) and [Fe(CN)6 ](3-) . For these systems, the reference calculations give deviations, when compared with experiment, of ≤1 eV in peak positions, ≤30% for the relative intensity of major peaks, and ≤50% for minor peaks. When compared with these deviations, the simulated spectra are sensitive to the number of final states, the inclusion of dynamical correlation, and the ionization potential electron affinity shift, in addition to the selection of the active space. The spectra are less sensitive to the quality of the basis set and even a double-ζ basis gives reasonable results. The inclusion of dynamical correlation through second-order perturbation theory can be done efficiently using the state-specific formalism without correlating the core orbitals. Although these observations are not directly transferable to other systems, they can, together with a cost analysis, aid in the design of RAS models and help to extend the use of this powerful approach to a wider range of transition metal systems. PMID:26502979

  6. Restricted active space calculations of L-edge X-ray absorption spectra: From molecular orbitals to multiplet states

    SciTech Connect

    Pinjari, Rahul V.; Delcey, Mickaël G.; Guo, Meiyuan; Lundberg, Marcus; Odelius, Michael

    2014-09-28

    The metal L-edge (2p → 3d) X-ray absorption spectra are affected by a number of different interactions: electron-electron repulsion, spin-orbit coupling, and charge transfer between metal and ligands, which makes the simulation of spectra challenging. The core restricted active space (RAS) method is an accurate and flexible approach that can be used to calculate X-ray spectra of a wide range of medium-sized systems without any symmetry constraints. Here, the applicability of the method is tested in detail by simulating three ferric (3d{sup 5}) model systems with well-known electronic structure, viz., atomic Fe{sup 3+}, high-spin [FeCl{sub 6}]{sup 3−} with ligand donor bonding, and low-spin [Fe(CN){sub 6}]{sup 3−} that also has metal backbonding. For these systems, the performance of the core RAS method, which does not require any system-dependent parameters, is comparable to that of the commonly used semi-empirical charge-transfer multiplet model. It handles orbitally degenerate ground states, accurately describes metal-ligand interactions, and includes both single and multiple excitations. The results are sensitive to the choice of orbitals in the active space and this sensitivity can be used to assign spectral features. A method has also been developed to analyze the calculated X-ray spectra using a chemically intuitive molecular orbital picture.

  7. Adenosine diphosphate restricts the protein remodeling activity of the Hsp104 chaperone to Hsp70 assisted disaggregation

    PubMed Central

    Kłosowska, Agnieszka; Chamera, Tomasz; Liberek, Krzysztof

    2016-01-01

    Hsp104 disaggregase provides thermotolerance in yeast by recovering proteins from aggregates in cooperation with the Hsp70 chaperone. Protein disaggregation involves polypeptide extraction from aggregates and its translocation through the central channel of the Hsp104 hexamer. This process relies on adenosine triphosphate (ATP) hydrolysis. Considering that Hsp104 is characterized by low affinity towards ATP and is strongly inhibited by adenosine diphosphate (ADP), we asked how Hsp104 functions at the physiological levels of adenine nucleotides. We demonstrate that physiological levels of ADP highly limit Hsp104 activity. This inhibition, however, is moderated by the Hsp70 chaperone, which allows efficient disaggregation by supporting Hsp104 binding to aggregates but not to non-aggregated, disordered protein substrates. Our results point to an additional level of Hsp104 regulation by Hsp70, which restricts the potentially toxic protein unfolding activity of Hsp104 to the disaggregation process, providing the yeast protein-recovery system with substrate specificity and efficiency in ATP consumption. DOI: http://dx.doi.org/10.7554/eLife.15159.001 PMID:27223323

  8. Nature of the promoter activated by C.PvuII, an unusual regulatory protein conserved among restriction-modification systems.

    PubMed

    Knowle, Dieter; Lintner, Robert E; Touma, Yara M; Blumenthal, Robert M

    2005-01-01

    A widely distributed family of small regulators, called C proteins, controls a subset of restriction-modification systems. The C proteins studied to date activate transcription of their own genes and that of downstream endonuclease genes; this arrangement appears to delay endonuclease expression relative to that of the protective methyltransferase when the genes enter a new cell. C proteins bind to conserved sequences called C boxes. In the PvuII system, the C boxes have been reported to extend from -23 to +3 relative to the transcription start for the gene for the C protein, an unexpected starting position relative to a bound activator. This study suggests that transcript initiation within the C boxes represents initial, C-independent transcription of pvuIICR. The major C protein-dependent transcript appears to be a leaderless mRNA starting farther downstream, at the initiation codon for the pvuIIC gene. This conclusion is based on nuclease S1 transcript mapping and the effects of a series of nested deletions in the promoter region. Furthermore, replacing the region upstream of the pvuIIC initiation codon with a library of random oligonucleotides, followed by selection for C-dependent transcription, yielded clones having sequences that resemble -10 promoter hexamers. The -35 hexamer of this promoter would lie within the C boxes. However, the spacing between C boxes/-35 and the apparent -10 hexamer can be varied by +/-4 bp with little effect. This suggests that, like some other activator-dependent promoters, PpvuIICR may not require a -35 hexamer. Features of this transcription activation system suggest explanations for its broad host range. PMID:15629920

  9. Deubiquitinase USP2a Sustains Interferons Antiviral Activity by Restricting Ubiquitination of Activated STAT1 in the Nucleus

    PubMed Central

    Liu, Jin; Yuan, Yukang; Cheng, Qiao; Zuo, Yibo; Qian, Liping; Guo, Tingting; Qian, Guanghui; Li, Lemin; Ge, Jun; Dai, Jianfeng; Xiong, Sidong; Zheng, Hui

    2016-01-01

    STAT1 is a critical transcription factor for regulating host antiviral defenses. STAT1 activation is largely dependent on phosphorylation at tyrosine 701 site of STAT1 (pY701-STAT1). Understanding how pY701-STAT1 is regulated by intracellular signaling remains a major challenge. Here we find that pY701-STAT1 is the major form of ubiquitinated-STAT1 induced by interferons (IFNs). While total STAT1 remains relatively stable during the early stages of IFNs signaling, pY701-STAT1 can be rapidly downregulated by the ubiquitin-proteasome system. Moreover, ubiquitinated pY701-STAT1 is located predominantly in the nucleus, and inhibiting nuclear import of pY701-STAT1 significantly blocks ubiquitination and downregulation of pY701-STAT1. Furthermore, we reveal that the deubiquitinase USP2a translocates into the nucleus and binds to pY701-STAT1, and inhibits K48-linked ubiquitination and degradation of pY701-STAT1. Importantly, USP2a sustains IFNs-induced pY701-STAT1 levels, and enhances all three classes of IFNs- mediated signaling and antiviral activity. To our knowledge, this is the first identified deubiquitinase that targets activated pY701-STAT1. These findings uncover a positive mechanism by which IFNs execute efficient antiviral signaling and function, and may provide potential targets for improving IFNs-based antiviral therapy. PMID:27434509

  10. Effects of blood flow restriction duration on muscle activation and microvascular oxygenation during low-volume isometric exercise.

    PubMed

    Cayot, Trent E; Lauver, Jakob D; Silette, Christopher R; Scheuermann, Barry W

    2016-07-01

    The purpose of the investigation was to observe how varying occlusion durations affected neuromuscular activation and microvascular oxygenation during low-volume isometric knee extension exercise. Healthy, recreationally active males performed isometric knee extension at a variety of submaximal intensities under different blood flow restriction (BFR) occlusion durations. The occlusion pressure (130% SBP) was applied either 5 min prior to exercise (PO), immediately prior to exercise (IO) or not during exercise (CON). Surface electromyography (sEMG) and near-infrared spectroscopy (NIRS) was used to record the neuromuscular activation and microvascular oxygenation of the knee extensors during exercise. No difference in sEMG was observed in the vastus lateralis or vastus medialis during any exercise condition or any submaximal intensity. PO elicited greater microvascular deoxygenation (deoxy-[Hb + Mb]) compared to CON (P≤0·05) at all submaximal intensities and also compared to IO at 20% maximal voluntary contraction (MVC). IO resulted in a greater deoxy-[Hb + Mb] response during low-intensity exercise (20% and 40% MVC) compared to CON (P≤0·05). These findings suggest that applying BFR 5 min before exercise can enhance the exercise-induced metabolic stress (i.e. deoxy-[Hb + Mb]), measured via NIRS, during low-intensity exercise (20% MVC) compared to applying BFR immediately prior to exercise. Furthermore, the increased metabolic stress observed during IO is attenuated during high-intensity (60% MVC, 80% MVC) exercise when compared to CON conditions. Knowledge of the changes in exercise-induced metabolic stress between the various occlusion durations may assist in developing efficient BFR exercise programmes. PMID:25564998

  11. Simulation of Active-Region-Scale Flux Emergence

    NASA Astrophysics Data System (ADS)

    Manchester, W.; van der Holst, B.

    2015-12-01

    Shear flows long observed in solar active regions are now understood to be a consequence of the Lorentz force that develops from a complex interaction between magnetic fields and the thermal pressure of the Sun's gravitationally stratified atmosphere. The shearing motions transport magnetic flux and energy from the submerged portion of the field to the corona providing the necessary energy for flares, filament eruptions and CMEs. To further examine this shearing process, we simulate flux emergence on the scale of active regions with a large-scale model of the near surface convection zone constructed on an adaptive spherical grid. This model is designed to simulate flux emerging on the scale of active regions from a depth of 30 Mm. Here, we show results of a twisted flux rope emerging through the hierarchy of granular convection, and examine the flow patterns that arise as the flux approaches the photosphere. We show how these organized flows driven by the Lorentz force cause the coronal field evolve to a highly non-potential configuration capable of driving solar eruptions such as CMEs and flares.

  12. How Large Scales Flows May Influence Solar Activity

    NASA Technical Reports Server (NTRS)

    Hathaway, D. H.

    2004-01-01

    Large scale flows within the solar convection zone are the primary drivers of the Sun's magnetic activity cycle and play important roles in shaping the Sun's magnetic field. Differential rotation amplifies the magnetic field through its shearing action and converts poloidal field into toroidal field. Poleward meridional flow near the surface carries magnetic flux that reverses the magnetic poles at about the time of solar maximum. The deeper, equatorward meridional flow can carry magnetic flux back toward the lower latitudes where it erupts through the surface to form tilted active regions that convert toroidal fields into oppositely directed poloidal fields. These axisymmetric flows are themselves driven by large scale convective motions. The effects of the Sun's rotation on convection produce velocity correlations that can maintain both the differential rotation and the meridional circulation. These convective motions can also influence solar activity directly by shaping the magnetic field pattern. While considerable theoretical advances have been made toward understanding these large scale flows, outstanding problems in matching theory to observations still remain.

  13. Interstitial Fluid Flow Intensity Modulates Endothelial Sprouting in Restricted Src-Activated Cell Clusters During Capillary Morphogenesis

    PubMed Central

    Hernández Vera, Rodrigo; Genové, Elsa; Alvarez, Lery; Borrós, Salvador; Kamm, Roger; Lauffenburger, Douglas

    2009-01-01

    Development of tissues in vitro with dimensions larger than 150 to 200 μm requires the presence of a functional vascular network. Therefore, we have studied capillary morphogenesis under controlled biological and biophysical conditions with the aim of promoting vascular structures in tissue constructs. We and others have previously demonstrated that physiological values of interstitial fluid flow normal to an endothelial monolayer in combination with vascular endothelial growth factor play a critical role during capillary morphogenesis by promoting cell sprouting. In the present work, we studied the effect that a range of interstitial flow velocities (0–50 μm/min) has in promoting the amount, length, and branching of developing sprouts during capillary morphogenesis. The number of capillary-like structures developed from human umbilical vein endothelial cell monolayers across the interstitial flow values tested was not significantly affected. Instead, the length and branching degree of the sprouts presented a significant maximum at flow velocities of 10 to 20 μm/min. More-over, at these same flow values, the phosphorylation level of Src also showed its peak. We discovered that capillary morphogenesis is restricted to patches of Src-activated cells (phosphorylated Src (pSrc)) at the monolayer, suggesting that the transduction pathway in charge of sensing the mechanical stimulus induced by flow is promoting predetermined mechanically sensitive areas (pSrc) to undergo capillary morphogenesis. PMID:18636940

  14. Time-dependent restricted-active-space self-consistent-field singles method for many-electron dynamics

    SciTech Connect

    Miyagi, Haruhide; Bojer Madsen, Lars

    2014-04-28

    The time-dependent restricted-active-space self-consistent-field singles (TD-RASSCF-S) method is presented for investigating TD many-electron dynamics in atoms and molecules. Adopting the SCF notion from the muticonfigurational TD Hartree-Fock (MCTDHF) method and the RAS scheme (single-orbital excitation concept) from the TD configuration-interaction singles (TDCIS) method, the TD-RASSCF-S method can be regarded as a hybrid of them. We prove that, for closed-shell N{sub e}-electron systems, the TD-RASSCF-S wave function can be fully converged using only N{sub e}/2 + 1 ⩽ M ⩽ N{sub e} spatial orbitals. Importantly, based on the TD variational principle, the converged TD-RASSCF-S wave function with M = N{sub e} is more accurate than the TDCIS wave function. The accuracy of the TD-RASSCF-S approach over the TDCIS is illustrated by the calculation of high-order harmonic generation spectra for one-dimensional models of atomic helium, beryllium, and carbon in an intense laser pulse. The electronic dynamics during the process is investigated by analyzing the behavior of electron density and orbitals. The TD-RASSCF-S method is accurate, numerically tractable, and applicable for large systems beyond the capability of the MCTDHF method.

  15. Cardiac Sirt1 mediates the cardioprotective effect of caloric restriction by suppressing local complement system activation after ischemia-reperfusion.

    PubMed

    Yamamoto, Tsunehisa; Tamaki, Kayoko; Shirakawa, Kohsuke; Ito, Kentaro; Yan, Xiaoxiang; Katsumata, Yoshinori; Anzai, Atsushi; Matsuhashi, Tomohiro; Endo, Jin; Inaba, Takaaki; Tsubota, Kazuo; Sano, Motoaki; Fukuda, Keiichi; Shinmura, Ken

    2016-04-15

    Caloric restriction (CR) confers cardioprotection against ischemia-reperfusion (I/R) injury. We previously found the essential roles of endothelial nitric oxide synthase in the development of CR-induced cardioprotection and Sirt1 activation during CR (Shinmura K, Tamaki K, Ito K, Yan X, Yamamoto T, Katsumata Y, Matsuhashi T, Sano M, Fukuda K, Suematsu M, Ishii I. Indispensable role of endothelial nitric oxide synthase in caloric restriction-induced cardioprotection against ischemia-reperfusion injury.Am J Physiol Heart Circ Physiol308: H894-H903, 2015). However, the exact mechanism by which Sirt1 in cardiomyocytes mediates the cardioprotective effect of CR remains undetermined. We subjected cardiomyocyte-specificSirt1knockout (CM-Sirt1(-/-)) mice and the corresponding control mice to either 3-mo ad libitum feeding or CR (-40%). Isolated perfused hearts were subjected to 25-min global ischemia, followed by 60-min reperfusion. The recovery of left ventricle function after I/R was improved, and total lactate dehydrogenase release into the perfusate during reperfusion was attenuated in the control mice treated with CR, but a similar cardioprotective effect of CR was not observed in the CM-Sirt1(-/-)mice. The expression levels of cardiac complement component 3 (C3) at baseline and the accumulation of C3 and its fragments in the ischemia-reperfused myocardium were attenuated by CR in the control mice, but not in the CM-Sirt1(-/-)mice. Resveratrol treatment also attenuated the expression levels of C3 protein in cultured neonatal rat ventricular cardiomyocytes. Moreover, the degree of myocardial I/R injury in conventionalC3knockout (C3(-/-)) mice treated with CR was similar to that in the ad libitum-fedC3(-/-)mice, although the expression levels of Sirt1 were enhanced by CR. These results demonstrate that cardiac Sirt1 plays an essential role in CR-induced cardioprotection against I/R injury by suppressing cardiac C3 expression. This is the first report suggesting that

  16. Activation of Nucleotide Oligomerization Domain 2 (NOD2) by Human Cytomegalovirus Initiates Innate Immune Responses and Restricts Virus Replication

    PubMed Central

    Kapoor, Arun; Forman, Michael; Arav-Boger, Ravit

    2014-01-01

    Nucleotide-binding oligomerization domain 2 (NOD2) is an important innate immune sensor of bacterial pathogens. Its induction results in activation of the classic NF-κB pathway and alternative pathways including type I IFN and autophagy. Although the importance of NOD2 in recognizing RNA viruses has recently been identified, its role in sensing DNA viruses has not been studied. We report that infection with human cytomegalovirus (HCMV) results in significant induction of NOD2 expression, beginning as early as 2 hours post infection and increasing steadily 24 hours post infection and afterwards. Infection with human herpesvirus 1 and 2 does not induce NOD2 expression. While the HCMV-encoded glycoprotein B is not required for NOD2 induction, a replication competent virion is necessary. Lentivirus-based NOD2 knockdown in human foreskin fibroblasts (HFFs) and U373 glioma cells leads to enhanced HCMV replication along with decreased levels of interferon beta (IFN-β) and the pro-inflammatory cytokine, IL8. NOD2 induction in HCMV-infected cells activates downstream NF-κB and interferon pathways supported by reduced nuclear localization of NF-κB and pIRF3 in NOD2 knockdown HFFs. Stable overexpression of NOD2 in HFFs restricts HCMV replication in association with increased levels of IFN-β and IL8. Similarly, transient overexpression of NOD2 in U373 cells or its downstream kinase, RIPK2, results in decreased HCMV replication and enhanced cytokine responses. However, overexpression of a mutant NOD2, 3020insC, associated with severe Crohn's disease, results in enhanced HCMV replication and decreased levels of IFN-β in U373 cells. These results show for the first time that NOD2 plays a significant role in HCMV replication and may provide a model for studies of HCMV recognition by the host cell and HCMV colitis in Crohn's disease. PMID:24671169

  17. Transient medium-scale wave activity in the summer stratosphere

    NASA Technical Reports Server (NTRS)

    Miles, T.; Grose, W. L.

    1986-01-01

    Observations of medium-scale transient wave activity in the middle-latitude Southern Hemisphere summer stratosphere are interpreted using isentropic potential vorticity (IPV) distributions inferred from temperature data from the Nimbus-7 Limb Infrared Monitor of the Stratosphere (LIMS) instrument. Despite problems with errors in reference-level synoptic height information, the derived IPV distributions clearly exhibit dynamically coherent signatures of eddy mixing due to medium-scale disturbances in the lower-middle stratosphere during early January 1979. The IPV distributions are shown to be strongly correlated with those of a contemporaneous set of isentropic maps of quasi-conservative tracers such as ozone and nitric acid. The results suggest that IPV maps inferred from satellite temperature data provide a useful diagnostic for studies of large-scale dynamics and/or transport in the extratropical stratosphere. Furthermore, the comparatively high vertical resolution of the LIMS data has enabled the vertical attenuation of Southern Hemisphere wave activity to be diagnosed in greater detail than could be achieved from nadir-viewing satellite information.

  18. The active commuting route environment scale (ACRES): development and evaluation

    PubMed Central

    2010-01-01

    Background Route environments can be a potentially important factor in influencing people's behaviours in relation to active commuting. To better understand these possible relationships, assessments of route environments are needed. We therefore developed a scale; the Active Commuting Route Environment Scale (ACRES), for the assessment of bicyclists' and pedestrians' perceptions of their commuting route environments. Here we will report on the development and the results of validity and reliability assessments thereof. Methods Active commuters (n = 54) were recruited when they bicycled in Stockholm, Sweden. Traffic planning and environmental experts from the Municipality of Stockholm were assembled to form an expert panel (n = 24). The active commuters responded to the scale on two occasions, and the expert panel responded to it once. To test criterion-related validity, differences in ratings of the inner urban and suburban environments of Greater Stockholm were compared between the experts and the commuters. Furthermore, four items were compared with existing objective measures. Test-retest reproducibility was assessed with three types of analysis: order effect, typical error and intraclass correlation. Results There was a concordance in sizes and directions of differences in ratings of inner urban and suburban environments between the experts and the commuters. Furthermore, both groups' ratings were in line with existing objectively measured differences between the two environmental settings. Order effects between test and retest were observed in 6 of 36 items. The typical errors ranged from 0.93 to 2.54, and the intraclass correlation coefficients ranged from 'moderate' (0.42) to 'almost perfect' (0.87). Conclusions The ACRES was characterized by considerable criterion-related validity and reasonable test-retest reproducibility. PMID:20609250

  19. Stoichiometry of soil enzyme activity at global scale.

    PubMed

    Sinsabaugh, Robert L; Lauber, Christian L; Weintraub, Michael N; Ahmed, Bony; Allison, Steven D; Crenshaw, Chelsea; Contosta, Alexandra R; Cusack, Daniela; Frey, Serita; Gallo, Marcy E; Gartner, Tracy B; Hobbie, Sarah E; Holland, Keri; Keeler, Bonnie L; Powers, Jennifer S; Stursova, Martina; Takacs-Vesbach, Cristina; Waldrop, Mark P; Wallenstein, Matthew D; Zak, Donald R; Zeglin, Lydia H

    2008-11-01

    Extracellular enzymes are the proximate agents of organic matter decomposition and measures of these activities can be used as indicators of microbial nutrient demand. We conducted a global-scale meta-analysis of the seven-most widely measured soil enzyme activities, using data from 40 ecosystems. The activities of beta-1,4-glucosidase, cellobiohydrolase, beta-1,4-N-acetylglucosaminidase and phosphatase g(-1) soil increased with organic matter concentration; leucine aminopeptidase, phenol oxidase and peroxidase activities showed no relationship. All activities were significantly related to soil pH. Specific activities, i.e. activity g(-1) soil organic matter, also varied in relation to soil pH for all enzymes. Relationships with mean annual temperature (MAT) and precipitation (MAP) were generally weak. For hydrolases, ratios of specific C, N and P acquisition activities converged on 1 : 1 : 1 but across ecosystems, the ratio of C : P acquisition was inversely related to MAP and MAT while the ratio of C : N acquisition increased with MAP. Oxidative activities were more variable than hydrolytic activities and increased with soil pH. Our analyses indicate that the enzymatic potential for hydrolyzing the labile components of soil organic matter is tied to substrate availability, soil pH and the stoichiometry of microbial nutrient demand. The enzymatic potential for oxidizing the recalcitrant fractions of soil organic material, which is a proximate control on soil organic matter accumulation, is most strongly related to soil pH. These trends provide insight into the biogeochemical processes that create global patterns in ecological stoichiometry and organic matter storage. PMID:18823393

  20. Meat Feeding Restricts Rapid Cold Hardening Response and Increases Thermal Activity Thresholds of Adult Blow Flies, Calliphora vicina (Diptera: Calliphoridae)

    PubMed Central

    2015-01-01

    Virtually all temperate insects survive the winter by entering a physiological state of reduced metabolic activity termed diapause. However, there is increasing evidence that climate change is disrupting the diapause response resulting in non-diapause life stages encountering periods of winter cold. This is a significant problem for adult life stages in particular, as they must remain mobile, periodically feed, and potentially initiate reproductive development at a time when resources should be diverted to enhance stress tolerance. Here we present the first evidence of protein/meat feeding restricting rapid cold hardening (RCH) ability and increasing low temperature activity thresholds. No RCH response was noted in adult female blow flies (Calliphora vicina Robineau-Desvoidy) fed a sugar, water and liver (SWL) diet, while a strong RCH response was seen in females fed a diet of sugar and water (SW) only. The RCH response in SW flies was induced at temperatures as high as 10°C, but was strongest following 3h at 0°C. The CTmin (loss of coordinated movement) and chill coma (final appendage twitch) temperature of SWL females (-0.3 ± 0.5°C and -4.9 ± 0.5°C, respectively) was significantly higher than for SW females (-3.2 ± 0.8°C and -8.5 ± 0.6°C). We confirmed this was not directly the result of altered extracellular K+, as activity thresholds of alanine-fed adults were not significantly different from SW flies. Instead we suggest the loss of cold tolerance is more likely the result of diverting resource allocation to egg development. Between 2009 and 2013 winter air temperatures in Birmingham, UK, fell below the CTmin of SW and SWL flies on 63 and 195 days, respectively, suggesting differential exposure to chill injury depending on whether adults had access to meat or not. We conclude that disruption of diapause could significantly impact on winter survival through loss of synchrony in the timing of active feeding and reproductive development with favourable

  1. Large-Scale Chaos and Fluctuations in Active Nematics

    NASA Astrophysics Data System (ADS)

    Ngo, Sandrine; Peshkov, Anton; Aranson, Igor S.; Bertin, Eric; Ginelli, Francesco; Chaté, Hugues

    2014-07-01

    We show that dry active nematics, e.g., collections of shaken elongated granular particles, exhibit large-scale spatiotemporal chaos made of interacting dense, ordered, bandlike structures in a parameter region including the linear onset of nematic order. These results are obtained from the study of both the well-known (deterministic) hydrodynamic equations describing these systems and of the self-propelled particle model they were derived from. We prove, in particular, that the chaos stems from the generic instability of the band solution of the hydrodynamic equations. Revisiting the status of the strong fluctuations and long-range correlations in the particle model, we show that the giant number fluctuations observed in the chaotic phase are a trivial consequence of density segregation. However anomalous, curvature-driven number fluctuations are present in the homogeneous quasiordered nematic phase and characterized by a nontrivial scaling exponent.

  2. Weight-Loss Induced Changes in Physical Activity and Activity Energy Expenditure in Overweight and Obese Subjects before and after Energy Restriction

    PubMed Central

    Bonomi, Alberto G.; Soenen, Stijn; Goris, Annelies H. C.; Westerterp, Klaas R.

    2013-01-01

    Activity energy expenditure (AEE) is the component of daily energy expenditure that is mainly influenced by the amount of physical activity (PA) and by the weight of the body displaced. This study aimed at analyzing the effect of weight loss on PA and AEE. The body weight and PA of 66 overweight and obese subjects were measured at baseline and after 12 weeks of 67% energy restriction. PA was measured using a tri-axial accelerometer for movement registration (Tracmor) and quantified in activity counts. Tracmor recordings were also processed using a classification algorithm to recognize 6 common activity types engaged in during the day. A doubly-labeled water validated equation based on Tracmor output was used to estimate AEE. After weight loss, body weight decreased by 13±4%, daily activity counts augmented by 9% (95% CI: +2%, +15%), and this increase was weakly associated with the decrease in body weight (R2 = 7%; P<0.05). After weight loss subjects were significantly (P<0.05) less sedentary (–26 min/d), and increased the time spent walking (+11 min/d) and bicycling (+4 min/d). However, AEE decreased by 0.6±0.4 MJ/d after weight loss. On average, a 2-hour/day reduction of sedentary time by increasing ambulatory and generic activities was required to restore baseline levels of AEE. In conclusion, after weight loss PA increased but the related metabolic demand did not offset the reduction in AEE due to the lower body weight. Promoting physical activity according to the extent of weight loss might increase successfulness of weight maintenance. PMID:23555733

  3. Spatiotemporal dynamics of large-scale brain activity

    NASA Astrophysics Data System (ADS)

    Neuman, Jeremy

    Understanding the dynamics of large-scale brain activity is a tough challenge. One reason for this is the presence of an incredible amount of complexity arising from having roughly 100 billion neurons connected via 100 trillion synapses. Because of the extremely high number of degrees of freedom in the nervous system, the question of how the brain manages to properly function and remain stable, yet also be adaptable, must be posed. Neuroscientists have identified many ways the nervous system makes this possible, of which synaptic plasticity is possibly the most notable one. On the other hand, it is vital to understand how the nervous system also loses stability, resulting in neuropathological diseases such as epilepsy, a disease which affects 1% of the population. In the following work, we seek to answer some of these questions from two different perspectives. The first uses mean-field theory applied to neuronal populations, where the variables of interest are the percentages of active excitatory and inhibitory neurons in a network, to consider how the nervous system responds to external stimuli, self-organizes and generates epileptiform activity. The second method uses statistical field theory, in the framework of single neurons on a lattice, to study the concept of criticality, an idea borrowed from physics which posits that in some regime the brain operates in a collectively stable or marginally stable manner. This will be examined in two different neuronal networks with self-organized criticality serving as the overarching theme for the union of both perspectives. One of the biggest problems in neuroscience is the question of to what extent certain details are significant to the functioning of the brain. These details give rise to various spatiotemporal properties that at the smallest of scales explain the interaction of single neurons and synapses and at the largest of scales describe, for example, behaviors and sensations. In what follows, we will shed some

  4. Simulations of iron K pre-edge X-ray absorption spectra using the restricted active space method.

    PubMed

    Guo, Meiyuan; Sørensen, Lasse Kragh; Delcey, Mickaël G; Pinjari, Rahul V; Lundberg, Marcus

    2016-01-28

    The intensities and relative energies of metal K pre-edge features are sensitive to both geometric and electronic structures. With the possibility to collect high-resolution spectral data it is important to find theoretical methods that include all important spectral effects: ligand-field splitting, multiplet structures, 3d-4p orbital hybridization, and charge-transfer excitations. Here the restricted active space (RAS) method is used for the first time to calculate metal K pre-edge spectra of open-shell systems, and its performance is tested against on six iron complexes: [FeCl6](n-), [FeCl4](n-), and [Fe(CN)6](n-) in ferrous and ferric oxidation states. The method gives good descriptions of the spectral shapes for all six systems. The mean absolute deviation for the relative energies of different peaks is only 0.1 eV. For the two systems that lack centrosymmetry [FeCl4](2-/1-), the ratios between dipole and quadrupole intensity contributions are reproduced with an error of 10%, which leads to good descriptions of the integrated pre-edge intensities. To gain further chemical insight, the origins of the pre-edge features have been analyzed with a chemically intuitive molecular orbital picture that serves as a bridge between the spectra and the electronic structures. The pre-edges contain information about both ligand-field strengths and orbital covalencies, which can be understood by analyzing the RAS wavefunction. The RAS method can thus be used to predict and rationalize the effects of changes in both the oxidation state and ligand environment in a number of hard X-ray studies of small and medium-sized molecular systems. PMID:26742851

  5. Restriction on an Energy-Dense Diet Improves Markers of Metabolic Health and Cellular Aging in Mice Through Decreasing Hepatic mTOR Activity

    PubMed Central

    Schloesser, Anke; Campbell, Graeme; Glüer, Claus-Christian; Rimbach, Gerald

    2015-01-01

    Abstract Dietary restriction (DR) on a normal low-fat diet improves metabolic health and may prolong life span. However, it is still uncertain whether restriction of an energy-dense, high-fat diet would also be beneficial and mitigate age-related processes. In the present study, we determined biomarkers of metabolic health, energy metabolism, and cellular aging in obesity-prone mice subjected to 30% DR on a high-fat diet for 6 months. Dietary-restricted mice had significantly lower body weights, less adipose tissue, lower energy expenditure, and altered substrate oxidation compared to their ad libitum–fed counterparts. Hepatic major urinary proteins (Mup) expression, which is linked to glucose and energy metabolism, and biomarkers of metabolic health, including insulin, glucose, cholesterol, and leptin/adiponectin ratio, were likewise reduced in high-fat, dietary-restricted mice. Hallmarks of cellular senescence such as Lamp2a and Hsc70 that mediate chaperone-mediated autophagy were induced and mechanistic target of rapamycin (mTOR) signaling mitigated upon high-fat DR. In contrast to DR applied in low-fat diets, anti-oxidant gene expression, proteasome activity, as well as 5′-adenosine monophosphate–activated protein kinase (AMPK) activation were not changed, suggesting that high-fat DR may attenuate some processes associated with cellular aging without the induction of cellular stress response or energy deprivation. PMID:25405871

  6. Large-scale cortical correlation structure of spontaneous oscillatory activity

    PubMed Central

    Hipp, Joerg F.; Hawellek, David J.; Corbetta, Maurizio; Siegel, Markus; Engel, Andreas K.

    2013-01-01

    Little is known about the brain-wide correlation of electrophysiological signals. Here we show that spontaneous oscillatory neuronal activity exhibits frequency-specific spatial correlation structure in the human brain. We developed an analysis approach that discounts spurious correlation of signal power caused by the limited spatial resolution of electrophysiological measures. We applied this approach to source estimates of spontaneous neuronal activity reconstructed from magnetoencephalography (MEG). Overall, correlation of power across cortical regions was strongest in the alpha to beta frequency range (8–32 Hz) and correlation patterns depended on the underlying oscillation frequency. Global hubs resided in the medial temporal lobe in the theta frequency range (4–6 Hz), in lateral parietal areas in the alpha to beta frequency range (8–23 Hz), and in sensorimotor areas for higher frequencies (32–45 Hz). Our data suggest that interactions in various large-scale cortical networks may be reflected in frequency specific power-envelope correlations. PMID:22561454

  7. Role of TRIM5α RING domain E3 ubiquitin ligase activity in capsid disassembly, reverse transcription blockade, and restriction of simian immunodeficiency virus.

    PubMed

    Kim, Jonghwa; Tipper, Christopher; Sodroski, Joseph

    2011-08-01

    The mammalian tripartite motif protein, TRIM5α, recognizes retroviral capsids entering the cytoplasm and blocks virus infection. Depending on the particular TRIM5α protein and retrovirus, complete disruption of the TRIM5α RING domain decreases virus-restricting activity to various degrees. TRIM5α exhibits RING domain-dependent E3 ubiquitin ligase activity, but the specific role of this activity in viral restriction is unknown. We created a panel of African green monkey TRIM5α (TRIM5α(AGM)) mutants, many of which are specifically altered in RING domain E3 ubiquitin ligase function, and characterized the phenotypes of these mutants with respect to restriction of simian and human immunodeficiency viruses (SIV(mac) and HIV-1, respectively). TRIM5α(AGM) ubiquitin ligase activity was essential for both the accelerated disassembly of SIV(mac) capsids and the disruption of reverse transcription. The levels of SIV(mac) particulate capsids in the cytosol of target cells expressing the TRIM5α variants strongly correlated with the levels of viral late reverse transcripts. RING-mediated ubiquitylation and B30.2(SPRY) domain-determined capsid binding independently contributed to the potency of SIV(mac) restriction by TRIM5α(AGM). In contrast, TRIM5α proteins attenuated in RING ubiquitin ligase function still accelerated HIV-1 capsid disassembly, inhibited reverse transcription, and blocked infection. Replacement of the helix-4/5 loop in the SIV(mac) capsid with the corresponding region of the HIV-1 capsid diminished the dependence of restriction on TRIM5α RING function. Thus, ubiquitylation mediated by the RING domain of TRIM5α(AGM) is essential for blocking SIV(mac) infection at the stage of capsid uncoating. PMID:21680520

  8. DISCOVERY OF FOUR kpc-SCALE BINARY ACTIVE GALACTIC NUCLEI

    SciTech Connect

    Liu Xin; Greene, Jenny E.; Strauss, Michael A.; Shen Yue

    2010-05-20

    We report the discovery of four kpc-scale binary active galactic nuclei (AGNs). These objects were originally selected from the Sloan Digital Sky Survey based on double-peaked [O III] {lambda}{lambda}4959, 5007 emission lines in their fiber spectra. The double peaks could result from pairing active supermassive black holes (SMBHs) in a galaxy merger or could be due to bulk motions of narrow-line region gas around a single SMBH. Deep near-infrared (NIR) images and optical slit spectra obtained from the Magellan 6.5 m and the Apache Point Observatory 3.5 m telescopes strongly support the binary SMBH scenario for the four objects. In each system, the NIR images reveal tidal features and double stellar components with a projected separation of several kpc, while optical slit spectra show two Seyfert 2 nuclei spatially coincident with the stellar components, with line-of-sight velocity offsets of a few hundred km s{sup -1}. These objects were drawn from a sample of only 43 objects, demonstrating the efficiency of this technique to find kpc-scale binary AGNs.

  9. Photonic crystal lasers using wavelength-scale embedded active region

    NASA Astrophysics Data System (ADS)

    Matsuo, Shinji; Sato, Tomonari; Takeda, Koji; Shinya, Akihiko; Nozaki, Kengo; Kuramochi, Eiichi; Taniyama, Hideaki; Notomi, Masaya; Fujii, Takuro; Hasebe, Koichi; Kakitsuka, Takaaki

    2014-01-01

    Lasers with ultra-low operating energy are desired for use in chip-to-chip and on-chip optical interconnects. If we are to reduce the operating energy, we must reduce the active volume. Therefore, a photonic crystal (PhC) laser with a wavelength-scale cavity has attracted a lot of attention because a PhC provides a large Q-factor with a small volume. To improve this device's performance, we employ an embedded active region structure in which the wavelength-scale active region is buried with an InP PhC slab. This structure enables us to achieve effective confinement of both carriers and photons, and to improve the thermal resistance of the device. Thus, we have obtained a large external differential quantum efficiency of 55% and an output power of -10 dBm by optical pumping. For electrical pumping, we use a lateral p-i-n structure that employs Zn diffusion and Si ion implantation for p-type and n-type doping, respectively. We have achieved room-temperature continuous-wave operation with a threshold current of 7.8 µA and a maximum 3 dB bandwidth of 16.2 GHz. The results of an experimental bit error rate measurement with a 10 Gbit s-1 NRZ signal reveal the minimum operating energy for transferring a single bit of 5.5 fJ. These results show the potential of this laser to be used for very short reach interconnects. We also describe the optimal design of cavity quality (Q) factor in terms of achieving a large output power with a low operating energy using a calculation based on rate equations. When we assume an internal absorption loss of 20 cm-1, the optimized coupling Q-factor is 2000.

  10. Habitual physical activity and plasma metabolomic patterns distinguish individuals with low vs. high weight loss during controlled energy restriction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Weight loss (WL) induced by energy restriction is highly variable even in controlled clinical trials. An integrative analysis of the plasma metabolome coupled to traditional clinical variables may reveal a WL “responder” phenotype. Therfore, we predicted WL in overweight and obese individuals on a...

  11. Habitual physical activity and plasma metabolomics patterns distinguish individuals with low- versus high-weight loss during controlled energy restriction

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Weight loss (WL) induced by energy restriction is highly variable even in controlled clinical trials. An integrative analysis of the plasma metabolome coupled to traditional clinical variables may reveal a WL “responder” phenotype. Therfore, we predicted WL in overweight and obese individuals on a...

  12. Measuring Parental Support for Children’s Physical Activity in White and African American Parents: The Activity Support Scale for Multiple Groups (ACTS-MG)

    PubMed Central

    Davison, Kirsten K.; Li, Kaigang; Baskin, Monica L.; Cox, Tiffany; Affuso, Olivia

    2010-01-01

    Objectives The Activity Support Scale (ACTS) was expanded for use with African American families. Its factorial invariance and internal reliability were examined for non-Hispanic white and African American parents. Methods The ACTS was modified to improve its applicability to African American families based on information from five focus groups with 27 African American parents of elementary school-aged children. Between 2006 and 2008, the revised scale was administered to 119 African American and 117 non-Hispanic white parents in northeastern NY and Alabama. Its factorial invariance across race/ethnicity and internal consistency were examined. Results Factor analysis of the revised scale, the Activity Support Scale for Multiple Groups (ACTS-MG), identified four parenting factors in white and African American parents including logistic support, modeling, use of community resources to promote physical activity (PA), and restriction of sedentary behaviors. Results supported the scale’s internal reliability and factorial invariance across race/ethnicity. Conclusion The ACTS-MG is appropriate for use with non-Hispanic white and African American families and will enable the extension of current research with white families to the examination of strategies supporting PA in African American families. Additional psychometric work with the ACTS-MG is encouraged. PMID:21111755

  13. COMMUNICATION: Neuron network activity scales exponentially with synapse density

    NASA Astrophysics Data System (ADS)

    Brewer, G. J.; Boehler, M. D.; Pearson, R. A.; DeMaris, A. A.; Ide, A. N.; Wheeler, B. C.

    2009-02-01

    Neuronal network output in the cortex as a function of synapse density during development has not been explicitly determined. Synaptic scaling in cortical brain networks seems to alter excitatory and inhibitory synaptic inputs to produce a representative rate of synaptic output. Here, we cultured rat hippocampal neurons over a three-week period to correlate synapse density with the increase in spontaneous spiking activity. We followed the network development as synapse formation and spike rate in two serum-free media optimized for either (a) neuron survival (Neurobasal/B27) or (b) spike rate (NbActiv4). We found that while synaptophysin synapse density increased linearly with development, spike rates increased exponentially in developing neuronal networks. Synaptic receptor components NR1, GluR1 and GABA-A also increase linearly but with more excitatory receptors than inhibitory. These results suggest that the brain's information processing capability gains more from increasing connectivity of the processing units than increasing processing units, much as Internet information flow increases much faster than the linear number of nodes and connections.

  14. Soil biological activity at European scale - two calculation concepts

    NASA Astrophysics Data System (ADS)

    Krüger, Janine; Rühlmann, Jörg

    2014-05-01

    The CATCH-C project aims to identify and improve the farm-compatibility of Soil Management Practices including to promote productivity, climate change mitigation and soil quality. The focus of this work concentrates on turnover conditions for soil organic matter (SOM). SOM is fundamental for the maintenance of quality and functions of soils while SOM storage is attributed a great importance in terms of climate change mitigation. The turnover conditions depend on soil biological activity characterized by climate and soil properties. To assess the turnover conditions two model concepts are applied: (I) Biological active time (BAT) regression approach derived from CANDY model (Franko & Oelschlägel 1995) expresses the variation of air temperature, precipitation and soil texture as a timescale and an indicator of biological activity for soil organic matter (SOM) turnover. (II) Re_clim parameter within the Introductory Carbon Balance Model (Andrén & Kätterer 1997) states the soil temperature and soil water to estimate soil biological activity. The modelling includes two strategies to cover the European scale and conditions. BAT was calculated on a 20x20 km grid basis. The European data sets of precipitation and air temperature (time period 1901-2000, monthly resolution), (Mitchell et al. 2004) were used to derive long-term averages. As we focus on agricultural areas we included CORINE data (2006) to extract arable land. The resulting BATs under co-consideration of the main soil textures (clay, silt, sand and loam) were investigated per environmental zone (ENZs, Metzger et al. 2005) that represents similar conditions for precipitation, temperature and relief to identify BAT ranges and hence turnover conditions for each ENZ. Re_clim was quantified by climatic time series of more than 250 weather stations across Europe presented by Klein Tank et al. (2002). Daily temperature, precipitation and potential evapotranspiration (maximal thermal extent) were used to calculate

  15. Production Scale-Up or Activated Carbons for Ultracapacitors

    SciTech Connect

    Dr. Steven D. Dietz

    2007-01-10

    Transportation use accounts for 67% of the petroleum consumption in the US. Electric and hybrid vehicles are promising technologies for decreasing our dependence on petroleum, and this is the objective of the FreedomCAR & Vehicle Technologies Program. Inexpensive and efficient energy storage devices are needed for electric and hybrid vehicle to be economically viable, and ultracapacitors are a leading energy storage technology being investigated by the FreedomCAR program. The most important parameter in determining the power and energy density of a carbon-based ultracapacitor is the amount of surface area accessible to the electrolyte, which is primarily determined by the pore size distribution. The major problems with current carbons are that their pore size distribution is not optimized for liquid electrolytes and the best carbons are very expensive. TDA Research, Inc. (TDA) has developed methods to prepare porous carbons with tunable pore size distributions from inexpensive carbohydrate based precursors. The use of low-cost feedstocks and processing steps greatly lowers the production costs. During this project with the assistance of Maxwell Technologies, we found that an impurity was limiting the performance of our carbon and the major impurity found was sulfur. A new carbon with low sulfur content was made and found that the performance of the carbon was greatly improved. We also scaled-up the process to pre-production levels and we are currently able to produce 0.25 tons/year of activated carbon. We could easily double this amount by purchasing a second rotary kiln. More importantly, we are working with MeadWestvaco on a Joint Development Agreement to scale-up the process to produce hundreds of tons of high quality, inexpensive carbon per year based on our processes.

  16. Synthesis and structure-activity relationship studies of O-biphenyl-3-yl carbamates as peripherally restricted fatty acid amide hydrolase inhibitors.

    PubMed

    Moreno-Sanz, Guillermo; Duranti, Andrea; Melzig, Laurin; Fiorelli, Claudio; Ruda, Gian Filippo; Colombano, Giampiero; Mestichelli, Paola; Sanchini, Silvano; Tontini, Andrea; Mor, Marco; Bandiera, Tiziano; Scarpelli, Rita; Tarzia, Giorgio; Piomelli, Daniele

    2013-07-25

    The peripherally restricted fatty acid amide hydrolase (FAAH) inhibitor URB937 (3, cyclohexylcarbamic acid 3'-carbamoyl-6-hydroxybiphenyl-3-yl ester) is extruded from the brain and spinal cord by the Abcg2 efflux transporter. Despite its inability to enter the central nervous system (CNS), 3 exerts profound antinociceptive effects in mice and rats, which result from the inhibition of FAAH in peripheral tissues and the consequent enhancement of anandamide signaling at CB1 cannabinoid receptors localized on sensory nerve endings. In the present study, we examined the structure-activity relationships (SAR) for the biphenyl region of compound 3, focusing on the carbamoyl and hydroxyl groups in the distal and proximal phenyl rings. Our SAR studies generated a new series of peripherally restricted FAAH inhibitors and identified compound 35 (cyclohexylcarbamic acid 3'-carbamoyl-5-hydroxybiphenyl-3-yl ester) as the most potent brain-impermeant FAAH inhibitor disclosed to date. PMID:23822179

  17. Affective Response to Physical Activity: Testing for Measurement Invariance of the Physical Activity Affect Scale across Active and Non-Active Individuals

    ERIC Educational Resources Information Center

    Carpenter, Laura C.; Tompkins, Sara Anne; Schmiege, Sarah J.; Nilsson, Renea; Bryan, Angela

    2010-01-01

    Affective responses to physical activity are assumed to play a role in exercise initiation and maintenance. The Physical Activity Affect Scale measures four dimensions of an individual's affective response to exercise. Group differences in the interpretation of scale items can impact the interpretability of mean differences, underscoring the need…

  18. Time-dependent multiconfiguration self-consistent-field method based on the occupation-restricted multiple-active-space model for multielectron dynamics in intense laser fields

    NASA Astrophysics Data System (ADS)

    Sato, Takeshi; Ishikawa, Kenichi L.

    2015-02-01

    The time-dependent multiconfiguration self-consistent-field method based on the occupation-restricted multiple-active-space model is proposed (TD-ORMAS) for multielectron dynamics in intense laser fields. Extending the previously proposed time-dependent complete-active-space self-consistent-field method [TD-CASSCF; Phys. Rev. A 88, 023402 (2013), 10.1103/PhysRevA.88.023402], which divides the occupied orbitals into core and active orbitals, the TD-ORMAS method further subdivides the active orbitals into an arbitrary number of subgroups and poses the occupation restriction by giving the minimum and maximum number of electrons distributed in each subgroup. This enables highly flexible construction of the configuration-interaction (CI) space, allowing a large-active-space simulation of dynamics, e.g., the core excitation or ionization. The equations of motion for both CI coefficients and spatial orbitals are derived based on the time-dependent variational principle, and an efficient algorithm is proposed to solve for the orbital time derivatives. In-depth descriptions of the computational implementation are given in a readily programmable manner. The numerical application to the one-dimensional lithium hydride cluster models demonstrates that the high flexibility of the TD-ORMAS framework allows for the cost-effective simulations of multielectron dynamics by exploiting systematic series of approximations to the TD-CASSCF method.

  19. Ultrafast Outflows: Galaxy-scale Active Galactic Nucleus Feedback

    NASA Astrophysics Data System (ADS)

    Wagner, A. Y.; Umemura, M.; Bicknell, G. V.

    2013-01-01

    We show, using global three-dimensional grid-based hydrodynamical simulations, that ultrafast outflows (UFOs) from active galactic nuclei (AGNs) result in considerable feedback of energy and momentum into the interstellar medium (ISM) of the host galaxy. The AGN wind interacts strongly with the inhomogeneous, two-phase ISM consisting of dense clouds embedded in a tenuous, hot, hydrostatic medium. The outflow floods through the intercloud channels, sweeps up the hot ISM, and ablates and disperses the dense clouds. The momentum of the UFO is primarily transferred to the dense clouds via the ram pressure in the channel flow, and the wind-blown bubble evolves in the energy-driven regime. Any dependence on UFO opening angle disappears after the first interaction with obstructing clouds. On kpc scales, therefore, feedback by UFOs operates similarly to feedback by relativistic AGN jets. Negative feedback is significantly stronger if clouds are distributed spherically rather than in a disk. In the latter case, the turbulent backflow of the wind drives mass inflow toward the central black hole. Considering the common occurrence of UFOs in AGNs, they are likely to be important in the cosmological feedback cycles of galaxy formation.

  20. ULTRAFAST OUTFLOWS: GALAXY-SCALE ACTIVE GALACTIC NUCLEUS FEEDBACK

    SciTech Connect

    Wagner, A. Y.; Umemura, M.; Bicknell, G. V.

    2013-01-20

    We show, using global three-dimensional grid-based hydrodynamical simulations, that ultrafast outflows (UFOs) from active galactic nuclei (AGNs) result in considerable feedback of energy and momentum into the interstellar medium (ISM) of the host galaxy. The AGN wind interacts strongly with the inhomogeneous, two-phase ISM consisting of dense clouds embedded in a tenuous, hot, hydrostatic medium. The outflow floods through the intercloud channels, sweeps up the hot ISM, and ablates and disperses the dense clouds. The momentum of the UFO is primarily transferred to the dense clouds via the ram pressure in the channel flow, and the wind-blown bubble evolves in the energy-driven regime. Any dependence on UFO opening angle disappears after the first interaction with obstructing clouds. On kpc scales, therefore, feedback by UFOs operates similarly to feedback by relativistic AGN jets. Negative feedback is significantly stronger if clouds are distributed spherically rather than in a disk. In the latter case, the turbulent backflow of the wind drives mass inflow toward the central black hole. Considering the common occurrence of UFOs in AGNs, they are likely to be important in the cosmological feedback cycles of galaxy formation.

  1. Regulatory circuit based on autogenous activation-repression: roles of C-boxes and spacer sequences in control of the PvuII restriction-modification system

    PubMed Central

    Mruk, Iwona; Rajesh, Preeti; Blumenthal, Robert M.

    2007-01-01

    Type II restriction-modification (R-M) systems comprise a restriction endonuclease (REase) and a protective methyltransferase (MTase). After R-M genes enter a new cell, MTase must appear before REase or the chromosome will be cleaved. PvuII and some other R-M systems achieve this delay by cotranscribing the REase gene with the gene for an autogenous transcription activator (the controlling or ‘C’ protein C.PvuII). This study reveals, through in vivo titration, that C.PvuII is not only an activator but also a repressor for its own gene. In other systems, this type of circuit can result in oscillatory behavior. Despite the use of identical, symmetrical C protein-binding sequences (C-boxes) in the left and right operators, C.PvuII showed higher in vitro affinity for OL than for OR, implicating the spacer sequences in this difference. Mutational analysis associated the repression with OR, which overlaps the promoter −35 hexamer but is otherwise dispensable for activation. A nonrepressing mutant exhibited poor establishment in new cells. Comparing promoter-operator regions from PvuII and 29 R-M systems controlled by C proteins revealed that the most-highly conserved sequence is the tetranucleotide spacer separating OL from OR. Any changes in that spacer reduced the stability of C.PvuII-operator complexes and abolished activation. PMID:17933763

  2. Regulatory circuit based on autogenous activation-repression: roles of C-boxes and spacer sequences in control of the PvuII restriction-modification system.

    PubMed

    Mruk, Iwona; Rajesh, Preeti; Blumenthal, Robert M

    2007-01-01

    Type II restriction-modification (R-M) systems comprise a restriction endonuclease (REase) and a protective methyltransferase (MTase). After R-M genes enter a new cell, MTase must appear before REase or the chromosome will be cleaved. PvuII and some other R-M systems achieve this delay by cotranscribing the REase gene with the gene for an autogenous transcription activator (the controlling or 'C' protein C.PvuII). This study reveals, through in vivo titration, that C.PvuII is not only an activator but also a repressor for its own gene. In other systems, this type of circuit can result in oscillatory behavior. Despite the use of identical, symmetrical C protein-binding sequences (C-boxes) in the left and right operators, C.PvuII showed higher in vitro affinity for O(L) than for O(R), implicating the spacer sequences in this difference. Mutational analysis associated the repression with O(R), which overlaps the promoter -35 hexamer but is otherwise dispensable for activation. A nonrepressing mutant exhibited poor establishment in new cells. Comparing promoter-operator regions from PvuII and 29 R-M systems controlled by C proteins revealed that the most-highly conserved sequence is the tetranucleotide spacer separating O(L) from O(R). Any changes in that spacer reduced the stability of C.PvuII-operator complexes and abolished activation. PMID:17933763

  3. Arylesterase activity is associated with antioxidant intake and paraoxonase-1 (PON1) gene methylation in metabolic syndrome patients following an energy restricted diet

    PubMed Central

    de la Iglesia, Rocio; Mansego, Maria L.; Sánchez-Muniz, Francisco J.; Zulet, M. Angeles; Martinez, J. Alfredo

    2014-01-01

    The arylesterase (ARE) activity linked to the paraoxonase-1 (PON1) gene is known to protect lipoproteins from oxidation and provide defense against metabolic syndrome (MetS) and cardiovascular diseases. The epigenetic regulation of enzymatic activities is gaining importance nowadays. This research aimed to assess the potential relationships between the ARE activity with the methylation levels of the PON1 gene transcriptional regulatory region, anthropometrics, biochemical markers and antioxidant dietary components. Forty-seven subjects (47 ± 10 y.o; BMI 36.2 ± 3.8 kg/m2; 46.8 % female) with MetS features, who followed a six-month energy-restricted dietary weight-loss intervention, were included in this study (www.clinicaltrials.gov; NCT01087086). Anthropometric, biochemical, enzymatic and dietary data were assessed using validated procedures. PON1 transcriptional regulatory region methylation was analyzed by a microarray technical approach. Volunteers reduced ARE activity in parallel with body weight (p = 0.005), BMI (p = 0.006), total fat mass (p = 0.020), diastolic blood pressure (p = 0.018), mean blood pressure (p = 0.022) and triglycerides (p = 0.014). Methylation levels of some CpG sites of the PON1 gene correlated negatively with ARE activity (p < 0.05). Interestingly, dietary vitamin C (p = 0.001), tocopherols (p = 0.009) and lycopene (p = 0.038) were positively associated with ARE activity and showed an inverse correlation (p = 0.004, p = 0.029 and p = 0.021, respectively) with the methylation of some selected CpG sites of the PON1 gene. In conclusion, ARE activity decreased in parallel with MetS-related markers associated to the energy restriction, while dietary antioxidants might enhance the ARE activity by lowering the PON1 gene methylation in patients with MetS features. PMID:26417268

  4. H11/HSPB8 Restricts HIV-2 Vpx to Restore the Anti-Viral Activity of SAMHD1

    PubMed Central

    Kudoh, Ayumi; Miyakawa, Kei; Matsunaga, Satoko; Matsushima, Yuki; Kosugi, Isao; Kimura, Hirokazu; Hayakawa, Satoshi; Sawasaki, Tatsuya; Ryo, Akihide

    2016-01-01

    Virus–host interactions play vital roles in viral replication and virus-induced pathogenesis. Viruses rely entirely upon host cells to reproduce progeny viruses; however, host factors positively or negatively regulate virus replication by interacting with viral proteins. The elucidation of virus–host protein interaction not only provides a better understanding of the molecular mechanisms by which host cells combat viral infections, but also facilitates the development of new anti-viral therapeutics. Identification of relevant host factors requires techniques that enable comprehensive characterization of virus–host protein interactions. In this study, we developed a proteomic approach to systematically identify human protein kinases that interact potently with viral proteins. For this purpose, we synthesized 412 full-length human protein kinases using the wheat germ cell-free protein synthesis system, and screened them for their association with a virus protein using the amplified luminescent proximity homogenous assay (AlphaScreen). Using this system, we attempted to discover a robust anti-viral host restriction mechanism targeting virus protein X (Vpx) of HIV-2. The screen identified H11/HSPB8 as a Vpx-binding protein that negatively regulates the stability and function of Vpx. Indeed, overexpression of H11/HSPB8 promoted the degradation of Vpx via the ubiquitin–proteasome pathway and inhibited its interaction with SAMHD1, a host restriction factor responsible for blocking replication of HIV. Conversely, targeted knockdown of H11/HSPB8 in human trophoblast cells, which ordinarily express high levels of this protein, restored the expression and function of Vpx, making the cells highly susceptible to viral replication. These results demonstrate that our proteomic approach represents a powerful tool for revealing virus–host interaction not yet identified by conventional methods. Furthermore, we showed that H11/HSPB8 could be a potential host regulatory

  5. Novel Role for Protein Inhibitor of Activated STAT 4 (PIAS4) in the Restriction of Herpes Simplex Virus 1 by the Cellular Intrinsic Antiviral Immune Response

    PubMed Central

    Conn, Kristen L.; Wasson, Peter; McFarlane, Steven; Tong, Lily; Brown, James R.; Grant, Kyle G.; Domingues, Patricia

    2016-01-01

    ABSTRACT Small ubiquitin-like modifier (SUMO) is used by the intrinsic antiviral immune response to restrict viral pathogens, such as herpes simplex virus 1 (HSV-1). Despite characterization of the host factors that rely on SUMOylation to exert their antiviral effects, the enzymes that mediate these SUMOylation events remain to be defined. We show that unconjugated SUMO levels are largely maintained throughout infection regardless of the presence of ICP0, the HSV-1 SUMO-targeted ubiquitin ligase. Moreover, in the absence of ICP0, high-molecular-weight SUMO-conjugated proteins do not accumulate if HSV-1 DNA does not replicate. These data highlight the continued importance for SUMO signaling throughout infection. We show that the SUMO ligase protein inhibitor of activated STAT 4 (PIAS4) is upregulated during HSV-1 infection and localizes to nuclear domains that contain viral DNA. PIAS4 is recruited to sites associated with HSV-1 genome entry through SUMO interaction motif (SIM)-dependent mechanisms that are destabilized by ICP0. In contrast, PIAS4 accumulates in replication compartments through SIM-independent mechanisms irrespective of ICP0 expression. Depletion of PIAS4 enhances the replication of ICP0-null mutant HSV-1, which is susceptible to restriction by the intrinsic antiviral immune response. The mechanisms of PIAS4-mediated restriction are synergistic with the restriction mechanisms of a characterized intrinsic antiviral factor, promyelocytic leukemia protein, and are antagonized by ICP0. We provide the first evidence that PIAS4 is an intrinsic antiviral factor. This novel role for PIAS4 in intrinsic antiviral immunity contrasts with the known roles of PIAS proteins as suppressors of innate immunity. IMPORTANCE Posttranslational modifications with small ubiquitin-like modifier (SUMO) proteins regulate multiple aspects of host immunity and viral replication. The protein inhibitor of activated STAT (PIAS) family of SUMO ligases is predominantly associated

  6. Measuring Enjoyment of Physical Activity in Children: Validation of the Physical Activity Enjoyment Scale

    PubMed Central

    2009-01-01

    This study sought to determine the reliability and validity of the Physical Activity Enjoyment Scale (PACES) in elementary school children. The sample consisted of 564 3rd grade students (M age = 8.72 ± .54; 268 male, 296 female) surveyed at the beginning of the fall semester. Results indicated that the PACES displayed good internal consistency and item-total correlations. Confirmatory factor analyses supported a unidimensional factor structure. Scores on the PACES were significantly correlated with task goal orientation (r = .65, p < .01), athletic competence (r = .23, p < .01), physical appearance (r = .20, p < .01), and self-reported physical activity (r = .16, p < .01). However, results of invariance analysis suggested the factor structure is variant across sex. The present findings suggest support for the validity of the PACES as a valid measure of enjoyment of physical activity in children; nevertheless, further research examining the invariance of the factor structure across sex is warranted. PMID:20209028

  7. Development of scales to assess children's perceptions of friend and parental influences on physical activity

    PubMed Central

    Jago, Russell; Fox, Kenneth R; Page, Angie S; Brockman, Rowan; Thompson, Janice L

    2009-01-01

    Background Many children do not meet physical activity guidelines. Parents and friends are likely to influence children's physical activity but there is a shortage of measures that are able to capture these influences. Methods A new questionnaire with the following three scales was developed: 1) Parental influence on physical activity; 2) Motives for activity with friends scale; and 3) Physical activity and sedentary group normative values. Content for each scale was informed by qualitative work. One hundred and seventy three, 10-11 year old children completed the new questionnaire twice, one week apart. Participants also wore an accelerometer for 5 days and mean minutes of moderate to vigorous physical activity, light physical activity and sedentary time per day were obtained. Test-retest reliability of the items was calculated and Principal Component analysis of the scales performed and sub-scales produced. Alphas were calculated for main scales and sub-scales. Correlations were calculated among sub-scales. Correlations between each sub-scale and accelerometer physical activity variables were calculated for all participants and stratified by sex. Results The Parental influence scale yielded four factors which accounted for 67.5% of the variance in the items and had good (α > 0.7) internal consistency. The Motives for physical activity scale yielded four factors that accounted for 66.1% and had good internal consistency. The Physical activity norms scale yielded 4 factors that accounted for 67.4% of the variance, with good internal consistency for the sub-scales and alpha of .642 for the overall scale. Associations between the sub-scales and physical activity differed by sex. Although only 6 of the 11 sub-scales were significantly correlated with physical activity there were a number of associations that were positively correlated >0.15 indicating that these factors may contribute to the explanation of children's physical activity. Conclusion Three scales that

  8. Design implications of extremely restricted patterning

    NASA Astrophysics Data System (ADS)

    Vaidyanathan, Kaushik; Liu, Renzhi; Liebmann, Lars; Lai, Kafai; Strojwas, Andzrej J.; Pileggi, Larry

    2014-07-01

    Escalating manufacturing cost and complexity is challenging the premise of affordable scaling. With lithography accounting for a large fraction of wafer costs, researchers are actively exploring several cost-effective alternative lithographic techniques, such as directed self-assembly, self-aligned multiple patterning, etc. However, most of the alternative lithographic techniques are restrictive, and it is important to understand the impact of such pattering restrictions on system-on-chip (SoC) design. To this end, we artificially restricted all layers in a 14 nm process to be pure gratings and observed that the pure gratings approach results in an inefficient SoC design with several process integration concerns. To come up with a technology definition that is mindful of designer requirements, it is essential to undertake a holistic design technology co-optimization (DTCO) considering several SoC design elements, such as standard cell logic, static random access memory bitcells, analog blocks, and physical synthesis. Our DTCO on the IBM 14 nm process with additional 10- and 7-nm node-like pattern restrictions leads us to converge on a set of critical pattern constructs that are required for an efficient and affordable SoC design.

  9. Validation of psychosocial scales for physical activity in university students.

    PubMed

    Tassitano, Rafael Miranda; de Farias Júnior, José Cazuza; Rech, Cassiano Ricardo; Tenório, Maria Cecília Marinho; Cabral, Poliana Coelho; da Silva, Giselia Alves Pontes

    2015-01-01

    OBJECTIVE Translate the Patient-centered Assessment and Counseling for Exercise questionnaire, adapt it cross-culturally and identify the psychometric properties of the psychosocial scales for physical activity in young university students. METHODS The Patient-centered Assessment and Counseling for Exercise questionnaire is made up of 39 items divided into constructs based on the social cognitive theory and the transtheoretical model. The analyzed constructs were, as follows: behavior change strategy (15 items), decision-making process (10), self-efficacy (6), support from family (4), and support from friends (4). The validation procedures were conceptual, semantic, operational, and functional equivalences, in addition to the equivalence of the items and of measurements. The conceptual, of items and semantic equivalences were performed by a specialized committee. During measurement equivalence, the instrument was applied to 717 university students. Exploratory factor analysis was used to verify the loading of each item, explained variance and internal consistency of the constructs. Reproducibility was measured by means of intraclass correlation coefficient. RESULTS The two translations were equivalent and back-translation was similar to the original version, with few adaptations. The layout, presentation order of the constructs and items from the original version were kept in the same form as the original instrument. The sample size was adequate and was evaluated by the Kaiser-Meyer-Olkin test, with values between 0.72 and 0.91. The correlation matrix of the items presented r < 0.8 (p < 0.05). The factor loadings of the items from all the constructs were satisfactory (> 0.40), varying between 0.43 and 0.80, which explained between 45.4% and 59.0% of the variance. Internal consistency was satisfactory (α ≥ 0.70), with support from friends being 0.70 and 0.92 for self-efficacy. Most items (74.3%) presented values above 0.70 for the reproducibility test

  10. Validation of psychosocial scales for physical activity in university students

    PubMed Central

    Tassitano, Rafael Miranda; de Farias, José Cazuza; Rech, Cassiano Ricardo; Tenório, Maria Cecília Marinho; Cabral, Poliana Coelho; da Silva, Giselia Alves Pontes

    2015-01-01

    OBJECTIVE Translate the Patient-centered Assessment and Counseling for Exercise questionnaire, adapt it cross-culturally and identify the psychometric properties of the psychosocial scales for physical activity in young university students. METHODS The Patient-centered Assessment and Counseling for Exercise questionnaire is made up of 39 items divided into constructs based on the social cognitive theory and the transtheoretical model. The analyzed constructs were, as follows: behavior change strategy (15 items), decision-making process (10), self-efficacy (6), support from family (4), and support from friends (4). The validation procedures were conceptual, semantic, operational, and functional equivalences, in addition to the equivalence of the items and of measurements. The conceptual, of items and semantic equivalences were performed by a specialized committee. During measurement equivalence, the instrument was applied to 717 university students. Exploratory factor analysis was used to verify the loading of each item, explained variance and internal consistency of the constructs. Reproducibility was measured by means of intraclass correlation coefficient. RESULTS The two translations were equivalent and back-translation was similar to the original version, with few adaptations. The layout, presentation order of the constructs and items from the original version were kept in the same form as the original instrument. The sample size was adequate and was evaluated by the Kaiser-Meyer-Olkin test, with values between 0.72 and 0.91. The correlation matrix of the items presented r < 0.8 (p < 0.05). The factor loadings of the items from all the constructs were satisfactory (> 0.40), varying between 0.43 and 0.80, which explained between 45.4% and 59.0% of the variance. Internal consistency was satisfactory (α ≥ 0.70), with support from friends being 0.70 and 0.92 for self-efficacy. Most items (74.3%) presented values above 0.70 for the reproducibility test

  11. A Combination of Activation and Repression by a Colinear Hox Code Controls Forelimb-Restricted Expression of Tbx5 and Reveals Hox Protein Specificity

    PubMed Central

    Nishimoto, Satoko; Minguillon, Carolina; Wood, Sophie; Logan, Malcolm P. O.

    2014-01-01

    Tight control over gene expression is essential for precision in embryonic development and acquisition of the regulatory elements responsible is the predominant driver for evolution of new structures. Tbx5 and Tbx4, two genes expressed in forelimb and hindlimb-forming regions respectively, play crucial roles in the initiation of limb outgrowth. Evolution of regulatory elements that activate Tbx5 in rostral LPM was essential for the acquisition of forelimbs in vertebrates. We identified such a regulatory element for Tbx5 and demonstrated Hox genes are essential, direct regulators. While the importance of Hox genes in regulating embryonic development is clear, Hox targets and the ways in which each protein executes its specific function are not known. We reveal how nested Hox expression along the rostro-caudal axis restricts Tbx5 expression to forelimb. We demonstrate that Hoxc9, which is expressed in caudal LPM where Tbx5 is not expressed, can form a repressive complex on the Tbx5 forelimb regulatory element. This repressive capacity is limited to Hox proteins expressed in caudal LPM and carried out by two separate protein domains in Hoxc9. Forelimb-restricted expression of Tbx5 and ultimately forelimb formation is therefore achieved through co-option of two characteristics of Hox genes; their colinear expression along the body axis and the functional specificity of different paralogs. Active complexes can be formed by Hox PG proteins present throughout the rostral-caudal LPM while restriction of Tbx5 expression is achieved by superimposing a dominant repressive (Hoxc9) complex that determines the caudal boundary of Tbx5 expression. Our results reveal the regulatory mechanism that ensures emergence of the forelimbs at the correct position along the body. Acquisition of this regulatory element would have been critical for the evolution of limbs in vertebrates and modulation of the factors we have identified can be molecular drivers of the diversity in limb morphology

  12. Method and apparatus for actively controlling a micro-scale flexural plate wave device

    DOEpatents

    Dohner, Jeffrey L.

    2001-01-01

    An actively controlled flexural plate wave device provides a micro-scale pump. A method of actively controlling a flexural plate wave device produces traveling waves in the device by coordinating the interaction of a magnetic field with actively controlled currents. An actively-controlled flexural plate wave device can be placed in a fluid channel and adapted for use as a micro-scale fluid pump to cool or drive micro-scale systems, for example, micro-chips, micro-electrical-mechanical devices, micro-fluid circuits, or micro-scale chemical analysis devices.

  13. Listening to patients: using verbal data in the validation of the Aberdeen Measures of Impairment, Activity Limitation and Participation Restriction (Ab-IAP)

    PubMed Central

    2010-01-01

    Background The purpose of the study was to evaluate the validity of the self-administered Aberdeen Measures of Impairment, Activity Limitation and Participation Restriction (Ab-IAP): by investigating how participants interpret and respond to questions using the cognitive interviewing technique. Methods Twenty patients with osteoarthritis of the knee or hip participated in a cognitive interview whilst completing the Ab-IAP. Interviews were conducted using the concurrent 'think aloud' design. All interviews were audio recorded and transcribed verbatim and analysed (i) using a standardised classification scheme to identify four types of response problems and (ii) thematically using the constant comparative technique. Results Participants used various response strategies when answering questions about impairment, activity limitations and participation restriction. Problems were judged to be present in 3.1% of participants' responses for the item Ab-IAP. Thematic analysis provided insight into the type and nature of problems people experienced when completing the Ab-IAP measures. The problems identified were mainly comprehension and response problems. Conclusions Participants had minimal difficulties completing the Ab-IAP; however those difficulties identified have prompted suggestions for improving the measures. The cognitive interviews produced results that were compatible with statistical analysis of the measures.. Cognitive interviewing was beneficial for testing the validity and acceptability of new Ab-IAP measures. The results demonstrates that the Ab-IAP, in addition to being theoretically-based and having good psychometric properties, elicits appropriate responses. PMID:20704724

  14. Differential inhibition of restriction enzyme cleavage by chromophore-modified analogues of the antitumour antibiotics mithramycin and chromomycin reveals structure-activity relationships.

    PubMed

    Mansilla, Sylvia; Garcia-Ferrer, Irene; Méndez, Carmen; Salas, José A; Portugal, José

    2010-05-15

    Differential cleavage at three restriction enzyme sites was used to determine the specific binding to DNA of the antitumour antibiotics mithramycin A (MTA), chromomycin A(3) (CRO) and six chromophore-modified analogues bearing shorter side chains attached at C-3, instead of the pentyl chain. All these antibiotics were obtained through combinatorial biosynthesis in the producer organisms. MTA, CRO and their six analogues showed differences in their capacity for inhibiting the rate of cleavage by restriction enzymes that recognize C/G-rich tracts. Changes in DNA melting temperature produced by these molecules were also analyzed, as well as their antiproliferative activities against a panel of colon, ovarian and prostate human carcinoma cell lines. Moreover, the cellular uptake of several analogues was examined to identify whether intracellular retention was related to cytotoxicity. These experimental approaches provided mutually consistent evidence of a seeming correlation between the strength of binding to DNA and the antiproliferative activity of the chromophore-modified molecules. Four of the analogues (mithramycin SK, mithramycin SDK, chromomycin SK and chromomycin SDK) showed promising biological profiles. PMID:20093108

  15. The Tobacco Control Scale: a new scale to measure country activity

    PubMed Central

    Joossens, L; Raw, M

    2006-01-01

    Objectives To quantify the implementation of tobacco control policies at country level using a new Tobacco Control Scale and to report initial results using the scale. Method A questionnaire sent to correspondents in 30 European countries, using a scoring system designed with the help of a panel of international tobacco control experts. Results The 30 countries are ranked by their total score on the scale out of a maximum possible score of 100. Only four countries (Ireland, United Kingdom, Norway, Iceland) scored 70 or more, with an eight point gap (most differences in scores are small) to the fifth country, Malta, on 62. Only 13 countries scored above 50, 11 of them from the European Union (EU), and the second largest points gap occurs between Denmark on 45 and Portugal on 39, splitting the table into three groups: 70 and above, 45 to 62, 39 and below. Ireland had the highest overall score, 74 out of 100, and Luxembourg was bottom with 26 points. However even Ireland, much praised for their ban on smoking in public places, did not increase tobacco taxes in 2005, for the first time since 1995. Conclusions Although the Tobacco Control Scale has limitations, this is the first time such a scale has been developed and applied to so many countries. We hope it will be useful in encouraging countries to strengthen currently weak areas of their tobacco control policy. PMID:16728757

  16. How High Is It? An Educator's Guide with Activities Focused on Scale Models of Distances.

    ERIC Educational Resources Information Center

    Rosenberg, Carla B.; Rogers, Melissa J. B.

    This guide focuses on scale models of distances. Activities also incorporate mathematics but can be used in science and technology grades 5-8 classes. The content of the book is divided into three sections: (1) Introductory Activities; (2) Core Activities; and (3) Activity/Assessment. Activities include: (1) KWL Chart; (2) Ball and String…

  17. Scales

    MedlinePlus

    Scales are a visible peeling or flaking of outer skin layers. These layers are called the stratum ... Scales may be caused by dry skin, certain inflammatory skin conditions, or infections. Eczema , ringworm , and psoriasis ...

  18. Measuring the Restrictiveness of Living Environments for Children and Youth: Reconceptualizing Restriction

    ERIC Educational Resources Information Center

    Rauktis, Mary E.; Huefner, Jonathan C.; O'Brien, Kirk; Pecora, Peter J.; Doucette, Ann; Thompson, Ronald W.

    2009-01-01

    The "Restrictiveness of Living Environment Scale" has long been the primary way to conceptualize the "restrictiveness" of a child's living situation. However, changes in systems of care and other factors have created a need to revisit how restrictiveness is conceptualized and measured. A measure was created to assess an environment's level of…

  19. Ribosomal frameshifting and dual-target antiactivation restrict quorum-sensing–activated transfer of a mobile genetic element

    PubMed Central

    Ramsay, Joshua P.; Tester, Laura G. L.; Major, Anthony S.; Sullivan, John T.; Edgar, Christina D.; Kleffmann, Torsten; Patterson-House, Jackson R.; Hall, Drew A.; Tate, Warren P.; Hynes, Michael F.; Ronson, Clive W.

    2015-01-01

    Symbiosis islands are integrative and conjugative mobile genetic elements that convert nonsymbiotic rhizobia into nitrogen-fixing symbionts of leguminous plants. Excision of the Mesorhizobium loti symbiosis island ICEMlSymR7A is indirectly activated by quorum sensing through TraR-dependent activation of the excisionase gene rdfS. Here we show that a +1 programmed ribosomal frameshift (PRF) fuses the coding sequences of two TraR-activated genes, msi172 and msi171, producing an activator of rdfS expression named Frameshifted excision activator (FseA). Mass-spectrometry and mutational analyses indicated that the PRF occurred through +1 slippage of the tRNAphe from UUU to UUC within a conserved msi172-encoded motif. FseA activated rdfS expression in the absence of ICEMlSymR7A, suggesting that it directly activated rdfS transcription, despite being unrelated to any characterized DNA-binding proteins. Bacterial two-hybrid and gene-reporter assays demonstrated that FseA was also bound and inhibited by the ICEMlSymR7A-encoded quorum-sensing antiactivator QseM. Thus, activation of ICEMlSymR7A excision is counteracted by TraR antiactivation, ribosomal frameshifting, and FseA antiactivation. This robust suppression likely dampens the inherent biological noise present in the quorum-sensing autoinduction circuit and ensures that ICEMlSymR7A transfer only occurs in a subpopulation of cells in which both qseM expression is repressed and FseA is translated. The architecture of the ICEMlSymR7A transfer regulatory system provides an example of how a set of modular components have assembled through evolution to form a robust genetic toggle that regulates gene transcription and translation at both single-cell and cell-population levels. PMID:25787256

  20. Similar time restriction for intracytoplasmic sperm injection and round spermatid injection into activated oocytes for efficient offspring production.

    PubMed

    Kishigami, Satoshi; Wakayama, Sayaka; Nguyen, Van Thuan; Wakayama, Teruhiko

    2004-06-01

    The injection of male haploid germ cells, such as spermatozoa and round spermatids, into preactivated mouse oocytes can result in the development of viable embryos and offspring. However, it is not clear how the timing of intracytoplasmic sperm injection (ICSI) and round spermatid injection (ROSI) affects the production of offspring. We carried out ICSI and ROSI every 20 min for up to 4 h after the activation of mouse oocytes by Sr(2+) and compared the late-stage development of ICSI- and ROSI- treated oocytes, including the formation of pronuclei, blastocyst formation, and offspring production. The rate of pronucleus formation (RPF) after carrying out ICSI started to decrease from >95% at 100 min following oocyte activation and declined to <20% by 180 min. In comparison, RPF by ROSI decreased gradually from >70% between 0 and 4 h after activation. The RPFs were closely correlated with blastocyst formation. Offspring production for both ICSI and ROSI decreased significantly when injections were conducted after 100 min, a time at which activated oocytes were in the early G1 stage of the cell cycle. These results suggest that spermatozoa and round spermatids have different potentials for inducing the formation of a male pronucleus in activated oocytes, but ICSI and ROSI are both subject to the same time constraint for the efficient production of offspring, which is determined by the cell cycle of the activated oocyte. PMID:14985245

  1. Calorie restriction does not restore brain mitochondrial function in P301L tau mice, but it does decrease mitochondrial F0F1-ATPase activity.

    PubMed

    Delic, Vedad; Brownlow, Milene; Joly-Amado, Aurelie; Zivkovic, Sandra; Noble, Kenyaria; Phan, Tam-Anh; Ta, Yen; Zhang, Yumeng; Bell, Stephen D; Kurien, Crupa; Reynes, Christian; Morgan, Dave; Bradshaw, Patrick C

    2015-07-01

    Calorie restriction (CR) has been shown to increase lifespan and delay aging phenotypes in many diverse eukaryotic species. In mouse models of Alzheimer's disease (AD), CR has been shown to decrease amyloid-beta and hyperphosphorylated tau levels and preserve cognitive function. Overexpression of human mutant tau protein has been shown to induce deficits in mitochondrial electron transport chain complex I activity. Therefore, experiments were performed to determine the effects of 4-month CR on brain mitochondrial function in Tg4510 mice, which express human P301L tau. Expression of mutant tau led to decreased ADP-stimulated respiratory rates, but not uncoupler-stimulated respiratory rates. The membrane potential was also slightly higher in mitochondria from the P301L tau mice. As shown previously, tau expression decreased mitochondrial complex I activity. The decreased complex I activity, decreased ADP-stimulated respiratory rate, and increased mitochondrial membrane potential occurring in mitochondria from Tg4510 mice were not restored by CR. However, the CR diet did result in a genotype independent decrease in mitochondrial F0F1-ATPase activity. This decrease in F0F1-ATPase activity was not due to lowered levels of the alpha or beta subunits of F0F1-ATPase. The possible mechanisms through which CR reduces the F0F1-ATPase activity in brain mitochondria are discussed. PMID:26048366

  2. Spatially restricted electrical activation of retinal ganglion cells in the rabbit retina by hexapolar electrode return configuration

    NASA Astrophysics Data System (ADS)

    Habib, Amgad G.; Cameron, Morven A.; Suaning, Gregg J.; Lovell, Nigel H.; Morley, John W.

    2013-06-01

    Objective. Visual prostheses currently in development aim to restore some form of vision to patients suffering from diseases such as age-related macular degeneration and retinitis pigmentosa. Most rely on electrically stimulating inner retinal cells via electrodes implanted on or near the retina, resulting in percepts of light termed ‘phosphenes’. Activation of spatially distinct populations of cells in the retina is key for pattern vision to be produced. To achieve this, the electrical stimulation must be localized, activating cells only in the direct vicinity of the stimulating electrode(s). With this goal in mind, a hexagonal return (hexapolar) configuration has been proposed as an alternative to the traditional monopolar or bipolar return configurations for electrically stimulating the retina. This study investigated the efficacy of the hexapolar configuration in localizing the activation of retinal ganglion cells (RGCs), compared to a monopolar configuration. Approach. Patch-clamp electrophysiology was used to measure the activation thresholds of RGCs in whole-mount rabbit retina to monopolar and hexapolar electrical stimulation, applied subretinally. Main results. Hexapolar activation thresholds for RGCs located outside the hex guard were found to be significantly (>2 fold) higher than those located inside the area of tissue bounded by the hex guard. The hexapolar configuration localized the activation of RGCs more effectively than its monopolar counterpart. Furthermore, no difference in hexapolar thresholds or localization was observed when using cathodic-first versus anodic-first stimulation. Significance. The hexapolar configuration may provide an improved method for electrically stimulating spatially distinct populations of cells in retinal tissue.

  3. Broken detailed balance at mesoscopic scales in active biological systems.

    PubMed

    Battle, Christopher; Broedersz, Chase P; Fakhri, Nikta; Geyer, Veikko F; Howard, Jonathon; Schmidt, Christoph F; MacKintosh, Fred C

    2016-04-29

    Systems in thermodynamic equilibrium are not only characterized by time-independent macroscopic properties, but also satisfy the principle of detailed balance in the transitions between microscopic configurations. Living systems function out of equilibrium and are characterized by directed fluxes through chemical states, which violate detailed balance at the molecular scale. Here we introduce a method to probe for broken detailed balance and demonstrate how such nonequilibrium dynamics are manifest at the mesosopic scale. The periodic beating of an isolated flagellum from Chlamydomonas reinhardtii exhibits probability flux in the phase space of shapes. With a model, we show how the breaking of detailed balance can also be quantified in stationary, nonequilibrium stochastic systems in the absence of periodic motion. We further demonstrate such broken detailed balance in the nonperiodic fluctuations of primary cilia of epithelial cells. Our analysis provides a general tool to identify nonequilibrium dynamics in cells and tissues. PMID:27126047

  4. 12 CFR 347.113 - Restrictions applicable to activities by a foreign organization in the United States.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...) Activities that are permissible for an Edge corporation in the United States under 12 CFR 211.6; or (ii... foreign organization in the United States. 347.113 Section 347.113 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY INTERNATIONAL BANKING §...

  5. 12 CFR 347.113 - Restrictions applicable to activities by a foreign organization in the United States.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...) Activities that are permissible for an Edge corporation in the United States under 12 CFR 211.6; or (ii... foreign organization in the United States. 347.113 Section 347.113 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY INTERNATIONAL BANKING §...

  6. 12 CFR 347.113 - Restrictions applicable to activities by a foreign organization in the United States.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...) Activities that are permissible for an Edge corporation in the United States under 12 CFR 211.6; or (ii... foreign organization in the United States. 347.113 Section 347.113 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY INTERNATIONAL BANKING §...

  7. 12 CFR 347.113 - Restrictions applicable to activities by a foreign organization in the United States.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) Activities that are permissible for an Edge corporation in the United States under 12 CFR 211.6; or (ii... foreign organization in the United States. 347.113 Section 347.113 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY INTERNATIONAL BANKING §...

  8. 12 CFR 347.113 - Restrictions applicable to activities by a foreign organization in the United States.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) Activities that are permissible for an Edge corporation in the United States under 12 CFR 211.6; or (ii... foreign organization in the United States. 347.113 Section 347.113 Banks and Banking FEDERAL DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY INTERNATIONAL BANKING §...

  9. Analysis and Management of Large-Scale Activities Based on Interface

    NASA Astrophysics Data System (ADS)

    Yang, Shaofan; Ji, Jingwei; Lu, Ligang; Wang, Zhiyi

    Based on the concepts of system safety engineering, life-cycle and interface that comes from American system safety standard MIL-STD-882E, and apply them to the process of risk analysis and management of large-scale activities. Identify the involved personnel, departments, funds and other contents throughout the life cycle of large-scale activities. Recognize and classify the ultimate risk sources of people, objects and environment of large-scale activities from the perspective of interface. Put forward the accident cause analysis model according to the previous large-scale activities' accidents and combine with the analysis of the risk source interface. Analyze the risks of each interface and summary various types of risks the large-scale activities faced. Come up with the risk management consciousness, policies and regulations, risk control and supervision departments improvement ideas.

  10. Glucose restriction decreases telomerase activity and enhances its inhibitor response on breast cancer cells: possible extra-telomerase role of BIBR 1532

    PubMed Central

    2014-01-01

    Background Considerable progress has been made to understand the association between lifestyle and diet in cancer initiation and promotion. Because excessive glucose consumption is a key metabolic hallmark of cancer cells, glucose restriction (GR) decreases the proliferation, and promotes the differentiation and transformation of cancer cells to quiescent cells. The immortality of cancerous cells is largely assured by telomerase, which is an interesting target for inhibition by BIBR 1532. In this study, we investigated the effect of GR on telomerase activity and on the efficacy of its inhibition by BIBR 1532. Methods Breast cancer MDA-MB 231 and MCF-7 cells were cultured in DMEM (Dulbecco’s modified eagle’s media) with 0, 1 or 4.5 g/l of glucose. The telomerase activity was measured via quantitative Real-Time PCR, and the two telomerase subunits were semi-quantified by RT-PCR. Proliferation test and mitochondrial metabolism were assessed via tetrazolium salt reduction and cell counts; apoptosis was assessed via caspase-3 quantification and flow cytometry. Results A decrease in the telomerase activity of more than 75% was associated with a significant reduction in the mRNA expression of its catalytic subunit hTERT (Reverse Transcriptase) and a decrease in the mitochondrial metabolism by more than 80% under restricted glucose conditions. In addition, GR increased the effect of BIBR 1532. Glucose deprivation induces apoptosis via BIBR 1532-mediated telomerase inhibition in triple negative breast cancer cells, as assessed by caspase-3 measurements and Annexin analysis. Conclusions Taken together, our results suggest that the effect of BIBR 1532 is potentiated by GR to induce triple negative breast cancer cell death. PMID:25089119

  11. Salt restriction leads to activation of adult renal mesenchymal stromal cell-like cells via prostaglandin E2 and E-prostanoid receptor 4.

    PubMed

    Yang, Yanqiang; Gomez, Jose A; Herrera, Marcela; Perez-Marco, Romelia; Repenning, Peter; Zhang, Zhiping; Payne, Alan; Pratt, Richard E; Koller, Beverly; Beierwaltes, William H; Coffman, Thomas; Mirotsou, Maria; Dzau, Victor J

    2015-05-01

    Despite the importance of juxtaglomerular cell recruitment in the pathophysiology of cardiovascular diseases, the mechanisms that underlie renin production under conditions of chronic stimulation remain elusive. We have previously shown that CD44+ mesenchymal-like cells (CD44+ cells) exist in the adult kidney. Under chronic sodium deprivation, these cells are recruited to the juxtaglomerular area and differentiate to new renin-expressing cells. Given the proximity of macula densa to the juxtaglomerular area and the importance of macula densa released prostanoids in renin synthesis and release, we hypothesized that chronic sodium deprivation induces macula densa release of prostanoids, stimulating renal CD44+ cell activation and differentiation. CD44+ cells were isolated from adult kidneys and cocultured with the macula densa cell line, MMDD1, in normal or low-sodium medium. Low sodium stimulated prostaglandin E2 production by MMDD1 and induced migration of CD44+ cells. These effects were inhibited by addition of a cyclooxygenase 2 inhibitor (NS398) or an E-prostanoid receptor 4 antagonist (AH23848) to MMDD1 or CD44+ cells, respectively. Addition of prostaglandin E2 to CD44+ cells increased cell migration and induced renin expression. In vivo activation of renal CD44+ cells during juxtaglomerular recruitment was attenuated in wild-type mice subjected to salt restriction in the presence of cyclooxygenase 2 inhibitor rofecoxib. Similar results were observed in E-prostanoid receptor 4 knockout mice subjected to salt restriction. These results show that the prostaglandin E2/E-prostanoid receptor 4 pathway plays a key role in the activation of renal CD44+ mesenchymal stromal cell-like cells during conditions of juxtaglomerular recruitment; highlighting the importance of this pathway as a key regulatory mechanism of juxtaglomerular recruitment. PMID:25776075

  12. Food restriction alters N'-propyl-4,5,6,7-tetrahydrobenzothiazole-2,6-diamine dihydrochloride (pramipexole)-induced yawning, hypothermia, and locomotor activity in rats: evidence for sensitization of dopamine D2 receptor-mediated effects.

    PubMed

    Collins, Gregory T; Calinski, Diane M; Newman, Amy Hauck; Grundt, Peter; Woods, James H

    2008-05-01

    Food restriction enhances sensitivity to the reinforcing effects of a variety of drugs of abuse including opiates, nicotine, and psychostimulants. Food restriction has also been shown to alter a variety of behavioral and pharmacological responses to dopaminergic agonists, including an increased sensitivity to the locomotor stimulatory effects of direct- and indirect-dopamine agonists, elevated extracellular dopamine levels in responses to psychostimulants, as well as suppression of agonist-induced yawning. Behavioral and molecular studies suggest that augmented dopaminergic responses observed in food-restricted animals result from a sensitization of the dopamine D2 receptor; however, little is known about how food restriction affects dopamine D3 receptor function. The current studies were aimed at better defining the effects of food restriction on D2 and D3 receptor function by assessing the capacity of N'-propyl-4,5,6,7-tetrahydrobenzothiazole-2,6-diamine dihydrochloride (pramipexole) to induce yawning, penile erection (PE), hypothermia, and locomotor activity in free-fed and food-restricted rats. Food restriction resulted in a suppression of pramipexole-induced yawning, a sensitized hypothermic response, and an enhanced locomotor response to pramipexole, effects that are suggestive of an enhanced D2 receptor activity; no effect on pramipexole-induced PE was observed. Antagonist studies further supported a food restriction-induced enhancement of the D2 receptor activity because the D2 antagonist 3-[4-(4-chlorophenyl)-4-hydroxypiperidin-l-yl]methyl-1H-indole (L741,626) recovered pramipexole-induced yawning to free-fed levels, whereas yawning and PE were suppressed following pretreatment with the D3 antagonist N-{4-[4-(2,3-dichlorophenyl)-piperazin-1-yl]-trans-but-2-enyl}-4-pyridine-2-yl-benzamide hydrochloride (PG01037). The results of the current studies suggest that food restriction sensitized rats to the D2-mediated effects of pramipexole while having no effect

  13. HDAC6-mediated EGFR stabilization and activation restrict cell response to sorafenib in non-small cell lung cancer cells.

    PubMed

    Wang, Zhihao; Hu, Pengchao; Tang, Fang; Xie, Conghua

    2016-05-01

    Sorafenib is a multi-targeted kinase inhibitor and has been the subject of extensive clinical research in advanced non-small cell lung cancer (NSCLC). However, sorafenib fails to improve overall survival of patients with advanced NSCLC. The molecular mechanisms that account for this phenomenon are unclear. Here we show that sorafenib treatment stabilizes epidermal growth factor receptor (EGFR) and activates EGFR pathway. Moreover, this is partly mediated by stabilization of histone deacetylase 6 (HDAC6), which has been shown to regulate EGFR endocytic trafficking and degradation. Overexpression of HDAC6 confers resistance to sorafenib in NSCLC cells. Inhibition of HDAC6 with selective inhibitors synergizes with sorafenib to kill NSCLC cells via inhibition of sorafenib-mediated EGFR pathway activation. Taken together, our findings might partly explain the failure of Phase III trial of sorafenib in improving overall survival of advanced NSCLC patients and bear possible implications for the improvement on the efficacy of sorafenib in treatment of NSCLC. PMID:27090797

  14. A model of EcoRII restriction endonuclease action: the active complex is most likely formed by one protein subunit and one DNA recognition site

    NASA Technical Reports Server (NTRS)

    Karpova, E. A.; Kubareva, E. A.; Shabarova, Z. A.

    1999-01-01

    To elucidate the mechanism of interaction of restriction endonuclease EcoRII with DNA, we studied by native gel electrophoresis the binding of this endonuclease to a set of synthetic DNA-duplexes containing the modified or canonical recognition sequence 5'-d(CCA/TGG)-3'. All binding substrate or substrate analogues tested could be divided into two major groups: (i) duplexes that, at the interaction with endonuclease EcoRII, form two types of stable complexes on native gel in the absence of Mg2+ cofactor; (ii) duplexes that form only one type of complex, observed both in the presence and absence of Mg2+. Unlike the latter, duplexes under the first group can be hydrolyzed by endonuclease. Data obtained suggest that the active complex is most likely formed by one protein subunit and one DNA recognition sequence. A model of EcoRII endonuclease action is presented.

  15. Lactobacillus fermentum CRL1446 Ameliorates Oxidative and Metabolic Parameters by Increasing Intestinal Feruloyl Esterase Activity and Modulating Microbiota in Caloric-Restricted Mice

    PubMed Central

    Russo, Matias; Fabersani, Emanuel; Abeijón-Mukdsi, María C.; Ross, Romina; Fontana, Cecilia; Benítez-Páez, Alfonso; Gauffin-Cano, Paola; Medina, Roxana B.

    2016-01-01

    The purpose of this study was to determine whether the administration of the feruloyl esterase (FE)-producing strain Lactobacillus fermentum CRL1446 enhances metabolic and oxidative parameters in caloric-restricted (CR) mice. Balb/c male mice were divided into ad libitum fed Group (ALF Group), CR diet Group (CR Group) and CR diet plus L. fermentum Group (CR-Lf Group). CR diet was administered during 45 days and CRL1446 strain was given in the dose of 108 cells/mL/day/mouse. FE activity was determined in intestinal mucosa and content at Day 1, 20 and 45. Triglyceride, total cholesterol, glucose, thiobarbituric acid reactive substances (TBARS) levels and glutathione reductase activity were determined in plasma. Gut microbiota was evaluated by high-throughput sequencing of 16S rRNA gene amplicons. At Day 45, total intestinal FE activity in CR-Lf Group was higher (p = 0.020) than in CR and ALF groups and an improvement in both metabolic (reductions in triglyceride (p = 0.0025), total cholesterol (p = 0.005) and glucose (p < 0.0001) levels) and oxidative (decrease of TBARS levels and increase of plasmatic glutathione reductase activity (p = 0.006)) parameters was observed, compared to ALF Group. CR diet increased abundance of Bacteroidetes and CRL1446 administration increased abundance of Bifidobacterium and Lactobacillus genus. L. fermentun CRL1446 exerted a bifidogenic effect under CR conditions. PMID:27399766

  16. Lactobacillus fermentum CRL1446 Ameliorates Oxidative and Metabolic Parameters by Increasing Intestinal Feruloyl Esterase Activity and Modulating Microbiota in Caloric-Restricted Mice.

    PubMed

    Russo, Matias; Fabersani, Emanuel; Abeijón-Mukdsi, María C; Ross, Romina; Fontana, Cecilia; Benítez-Páez, Alfonso; Gauffin-Cano, Paola; Medina, Roxana B

    2016-01-01

    The purpose of this study was to determine whether the administration of the feruloyl esterase (FE)-producing strain Lactobacillus fermentum CRL1446 enhances metabolic and oxidative parameters in caloric-restricted (CR) mice. Balb/c male mice were divided into ad libitum fed Group (ALF Group), CR diet Group (CR Group) and CR diet plus L. fermentum Group (CR-Lf Group). CR diet was administered during 45 days and CRL1446 strain was given in the dose of 10⁸ cells/mL/day/mouse. FE activity was determined in intestinal mucosa and content at Day 1, 20 and 45. Triglyceride, total cholesterol, glucose, thiobarbituric acid reactive substances (TBARS) levels and glutathione reductase activity were determined in plasma. Gut microbiota was evaluated by high-throughput sequencing of 16S rRNA gene amplicons. At Day 45, total intestinal FE activity in CR-Lf Group was higher (p = 0.020) than in CR and ALF groups and an improvement in both metabolic (reductions in triglyceride (p = 0.0025), total cholesterol (p = 0.005) and glucose (p < 0.0001) levels) and oxidative (decrease of TBARS levels and increase of plasmatic glutathione reductase activity (p = 0.006)) parameters was observed, compared to ALF Group. CR diet increased abundance of Bacteroidetes and CRL1446 administration increased abundance of Bifidobacterium and Lactobacillus genus. L. fermentun CRL1446 exerted a bifidogenic effect under CR conditions. PMID:27399766

  17. Scaling and Transition of the Explosive Activity at Stromboli Volcano

    NASA Astrophysics Data System (ADS)

    Ripepe, M.; Marchetti, E.; Genco, R.; Lacanna, G.; Delle Donne, D.; Valade, S.; Ulivieri, G.

    2014-12-01

    Explosive activity at Stromboli volcano covers a wide energetic and temporal spectrum, spanning from small puffing to violent paroxysms and with the corresponding mass discharge rate ranging 7 orders of magnitude. At the lowest end, puffing activity is characterized by discrete small pulses of gas and fragments with limited excess pressure, driving gas and ejecta at the rate of 1 kg/s few meters high above the vents and repeating almost persistently at the rate of ~ 1 event every 2 seconds. With increasing mass discharge rate ordinary explosive activity (103 kg/s) is repeating every ~ few minutes ejecting hot lava fragments at ~200 m height whereas larger (Mayor) explosions are occurring every year with a mass eruptive rate of 105 kg/s driving progressively higher eruptive clouds at ~500 m above the vent. At the other end of the activity, the paroxysms have a mass discharge rate of 107 kg/s, driving the eruptive column up to few km above the crater and repeating at a rate of one event every ~10 years. Clear limits among these different eruptive styles have not been defined and the dynamics driving this broad explosive spectrum is still debated. We show how seismic, ground tilt and infrasonic data collected at Stromboli since 2008 for a total of ~24000 events provide a geophysical-based classification of explosive activity at Stromboli volcano highlighting changes in eruptive dynamics.

  18. Metabolic Benefit of Chronic Caloric Restriction and Activation of Hypothalamic AGRP/NPY Neurons in Male Mice Is Independent of Ghrelin.

    PubMed

    Rogers, Nicole H; Walsh, Heidi; Alvarez-Garcia, Oscar; Park, Seongjoon; Gaylinn, Bruce; Thorner, Michael O; Smith, Roy G

    2016-04-01

    Aging is associated with attenuated ghrelin signaling. During aging, chronic caloric restriction (CR) produces health benefits accompanied by enhanced ghrelin production. Ghrelin receptor (GH secretagogue receptor 1a) agonists administered to aging rodents and humans restore the young adult phenotype; therefore, we tested the hypothesis that the metabolic benefits of CR are mediated by endogenous ghrelin. Three month-old male mice lacking ghrelin (Ghrelin-/-) or ghrelin receptor (Ghsr-/-), and their wild-type (WT) littermates were randomly assigned to 2 groups: ad libitum (AL) fed and CR, where 40% food restriction was introduced gradually to allow Ghrelin-/- and Ghsr-/- mice to metabolically adapt and avoid severe hypoglycemia. Twelve months later, plasma ghrelin, metabolic parameters, ambulatory activity, hypothalamic and liver gene expression, as well as body composition were measured. CR increased plasma ghrelin and des-acyl ghrelin concentrations in WT and Ghsr-/- mice. CR of WT, Ghsr-/-, and Ghrelin-/- mice markedly improved metabolic flexibility, enhanced ambulatory activity, and reduced adiposity. Inactivation of Ghrelin or Ghsr had no effect on AL food intake or food anticipatory behavior. In contrast to the widely held belief that endogenous ghrelin regulates food intake, CR increased expression of hypothalamic Agrp and Npy, with reduced expression of Pomc across genotypes. In the AL context, ablation of ghrelin signaling markedly inhibited liver steatosis, which correlated with reduced Pparγ expression and enhanced Irs2 expression. Although CR and administration of GH secretagogue receptor 1a agonists both benefit the aging phenotype, we conclude the benefits of chronic CR are a consequence of enhanced metabolic flexibility independent of endogenous ghrelin or des-acyl ghrelin signaling. PMID:26812158

  19. Long-term calorie restriction decreases metabolic cost of movement and prevents decrease of physical activity during aging in the rhesus monkeys

    PubMed Central

    Yamada, Yosuke; Colman, Ricki J; Kemnitz, Joseph W.; Baum, Scott T.; Anderson, Rozalyn M.; Weindruch, Richard; Schoeller, Dale A.

    2013-01-01

    Background Short-term (<1 year) calorie restriction (CR) has been reported to decrease physical activity and metabolic rate in humans and non-human primate models; however, studies examining the very long-term (>10 year) effect of CR on these parameters are lacking. Objective The objective of this study was to examine metabolic and behavioral adaptations to long-term CR longitudinally in rhesus macaques. Design Eighteen (10 male, 8 female) control (C) and 24 (14 male, 10 female) age matched CR rhesus monkeys between 19.6 and 31.9 years old were examined after 13 and 18 years of moderate adult-onset CR. Energy expenditure (EE) was examined by doubly labeled water (DLW; TEE) and respiratory chamber (24hrEE). Physical activity was assessed both by metabolic equivalent (MET) in a respiratory chamber and by an accelerometer. Metabolic cost of movements during 24h were also calculated. Age and fat-free mass were included as covariates. Results Adjusted total and 24hr EE were not different between C and CR. Sleeping metabolic rate was significantly lower, and physical activity level was higher in CR than in C independent from the CR-induced changes in body composition. The duration of physical activity above 1.6 METs was significantly higher in CR than in C, and CR had significantly higher accelerometer activity counts than C. Metabolic cost of movements during 24h were significantly lower in CR than in C. The accelerometer activity counts were significantly decreased after seven years in C animals, but not in CR animals. Conclusions The results suggest that long-term CR decreases basal metabolic rate, but maintains higher physical activity with lower metabolic cost of movements compared with C. PMID:23954367

  20. Validity Evidence for the State Mindfulness Scale for Physical Activity

    ERIC Educational Resources Information Center

    Cox, Anne E.; Ullrich-French, Sarah; French, Brian F.

    2016-01-01

    Being attentive to and aware of one's experiences in the present moment with qualities of acceptance and openness reflects the state of mindfulness. Positive associations exist between state mindfulness and state autonomous motivation for everyday activities. Though this suggests that state mindfulness links with adaptive motivational experiences,…

  1. Scaling of strontium-vapor laser active volume

    NASA Astrophysics Data System (ADS)

    Soldatov, A. N.; Polunin, Yu. P.

    2008-01-01

    Variations in the energy performance of a self-terminating Sr-vapor laser (SrVL) are examined. The active laser volume is varied between 20 and 650 cm 3. A linear relation is revealed between the average power delivered by the SrVL and its active volume. The SrVL efficiency is found to increase with active volume and to be comparable with that of a copper-vapor laser for an active volume V = 650 cm 3 (0.45 %). As the volume is increased, the total lasing pulse duration increases from 30 to 120 ns. The beam divergence problems associated with the use of a Fabry-Perot cavity or an unstable resonator of the telescopic type are discussed. A total average power of 13.5 W is obtained from V = 650 cm 3 at a lasing PRR F = 19 kHz. The output power generated at different laser wavelengths is as follows: 10.4 W at λ = 6.456 μm, 2.6 W at λ = 3 μm, and 0.5 W at λ = 1 μm. The wavelength dependence of the lasing pulse duration is considered.

  2. Phenotypic debrisoquine 4-hydroxylase activity among extensive metabolizers is unrelated to genotype as determined by the Xba-I restriction fragment length polymorphism.

    PubMed Central

    Turgeon, J; Evans, W E; Relling, M V; Wilkinson, G R; Roden, D M

    1991-01-01

    1. The major pathway for 4-hydroxylation of debrisoquine in man is polymorphic and under genetic control. More than 90% of subjects (extensive metabolizers, EMs) have active debrisoquine 4-hydroxylase (cytochrome P450IID6) while in the remainder (poor metabolizers, PMs), cytochrome P450IID6 activity is greatly impaired. 2. Within the EM group, cytochrome P450IID6-mediated metabolism of a range of substrates varies widely. Some of this intra-phenotype non-uniformity may be explained by the presence of two subsets of subjects with different genotypes (heterozygotes and homozygotes). 3. Cytochrome P450IID6 substrates have not differentiated between these two genotypes. However, a restriction fragment length polymorphism (RFLP) which identifies mutant alleles of cytochrome P450IID6 locus has been described and can definitively assign genotype in some heterozygous EM subjects. 4. In this study, we used RFLP analysis and encainide as a model substrate to determine if non-uniformity in cytochrome P450IID6 activity among EMs is related to genotype. We tested the hypothesis that heterozygotes exhibit intermediate metabolic activity and that homozygous dominants exhibit the highest activity. We proposed encainide as a useful substrate for this purpose since cytochrome P450IID6 catalyzes not only its biotransformation to O-desmethyl encainide (ODE) but also the subsequent metabolism of ODE to 3-methoxy-O-desmethyl encainide (MODE). 5. A single 50 mg oral dose of encainide was administered to 139 normal volunteers and 14 PMs were identified. Urinary ratios among encainide, ODE and MODE in the remaining 125 EM subjects revealed a wide range of cytochrome P450IID6 activity. However, Southern blotting of genomic DNA digested with XbaI identified obligate heterozygotes in both extremes of all ratio distributions.(ABSTRACT TRUNCATED AT 250 WORDS) Images Figure 2 PMID:1685663

  3. Development of the chronic obstructive pulmonary disease activity rating scale: reliability, validity and factorial structure.

    PubMed

    Morimoto, Michiko; Takai, Kenichi; Nakajima, Kazuo; Kagawa, Koujiro

    2003-03-01

    The purpose of the present study was to develop the Chronic Obstructive Pulmonary Disease (COPD) Activity Rating Scale (CARS) to measure life-related activity in patients with COPD, and to confirm its reliability and constructive validity in a factorial structure model. The subjects consisted of 114 patients with COPD. An 88-item life-related activity list, generated previously from a literature review, was administered. The secondary structural model consisted of four factors with 12 items. The results of the confirmatory factor analysis by structural equation modeling showed the fit criteria to be statistically significant. The internal consistency of the 12 items was highly reliable (Cronbach's alpha = 0.924). The CARS score was correlated with pulmonary function tests, breathlessness, and the health-related quality of life (QOL) scales in Pearson correlation coefficient. The results suggest that the COPD Activity Rating Scale is a valid scale for the assessment of life-related activity in patients with COPD. PMID:12603718

  4. The Behavioral Activation for Depression Scale-Short Form: Development and Validation

    ERIC Educational Resources Information Center

    Manos, Rachel C.; Kanter, Jonathan W.; Luo, Wen

    2011-01-01

    Following a landmark component analysis of cognitive therapy by Jacobson and colleagues (1996), there has been renewed interest in behavioral activation (BA) treatments for depression. The Behavioral Activation for Depression Scale (BADS) was developed to measure when and how clients become activated over the course of BA treatment. Multiple…

  5. Factor- and Item-Level Analyses of the 38-Item Activities Scale for Kids-Performance

    ERIC Educational Resources Information Center

    Bagley, Anita M.; Gorton, George E.; Bjornson, Kristie; Bevans, Katherine; Stout, Jean L.; Narayanan, Unni; Tucker, Carole A.

    2011-01-01

    Aim: Children and adolescents highly value their ability to participate in relevant daily life and recreational activities. The Activities Scale for Kids-performance (ASKp) instrument measures the frequency of performance of 30 common childhood activities, and has been shown to be valid and reliable. A revised and expanded 38-item ASKp (ASKp38)…

  6. Solid discharge and landslide activity at basin scale

    NASA Astrophysics Data System (ADS)

    Ardizzone, F.; Guzzetti, F.; Iadanza, C.; Rossi, M.; Spizzichino, D.; Trigila, A.

    2012-04-01

    This work presents a preliminary analysis aimed at understanding the relationship between landslide sediment supply and sediment yield at basin scale in central and southern Italy. A database of solid discharge measurements regarding 116 gauging stations, located along the Apennines chain in Italy, has been compiled by investigating the catalogues, named Annali Idrologici, published by Servizio Idrografico e Mareografico Italiano in the period from 1917 to 1997. The database records several information about the 116 gauging stations, and especially reports the sediment yield monthly measurements (103 ton) and the catchments area (km2). These data have been used to calculate the average solid yield and the normalized solid yield for each station in the observation period. The Italian Landslide Inventory (Progetto IFFI) has been used to obtained the size of the landslides, in order to estimate the landslide mobilization rates. The IFFI Project funded by the Italian Government is realized by ISPRA (Italian National Institute for Environmental Protection and Research - Geological Survey of Italy) in partnership with the 21 Regions and Self Governing Provinces. 21 of the 116 gauging stations and the related catchments have been selected on the basis of the length of the solid discharge observation period and excluding the catchments with dams located upstream the stations. The landslides inside the selected catchments have been extracted from the IFFI inventory, calculating the planimetric area of each landslide. Considering both the shallow and deep landslides, the landslide volume has been estimated using an empirical power law relation (landslide area vs. volume). The total landslide volume in the study areas and the average sediment yield measured at the gauging stations have been compared, analysing the behaviour of the basins which drainage towards the Tyrrhenian sea and the basins which drainage towards the Adriatic sea.

  7. Social Support and Peer Norms Scales for Physical Activity in Adolescents

    PubMed Central

    Ling, Jiying; Robbins, Lorraine B.; Resnicow, Ken; Bakhoya, Marion

    2015-01-01

    Objectives To evaluate psychometric properties of a Social Support and Peer Norms Scale in 5th-7th grade urban girls. Methods Baseline data from 509 girls and test-retest data from another 94 girls in the Midwestern US were used. Results Cronbach's alpha was .83 for the Social Support Scale and .72 for the Peer Norms Scale, whereas test-re-test reliability was .78 for both scales. Exploratory factor analysis suggested a single factor structure for the Social Support Scale, and a 3-factor structure for the Peer Norms Scale. Social support was correlated with accelerometer-measured physical activity (r = .13, p = .006), and peer norms (r = .50, p < .0001). Conclusions Both scales have adequate psychometric properties. PMID:25207514

  8. Passive and Active Vibrations Allow Self-Organization in Large-Scale Electromechanical Systems

    NASA Astrophysics Data System (ADS)

    Buscarino, Arturo; Fortuna, Carlo Famoso Luigi; Frasca, Mattia

    2016-06-01

    In this paper, the role of passive and active vibrations for the control of nonlinear large-scale electromechanical systems is investigated. The mathematical model of the system is discussed and detailed experimental results are shown in order to prove that coupling the effects of feedback and vibrations elicited by proper control signals makes possible to regularize imperfect uncertain large-scale systems.

  9. Active assembly for large-scale manufacturing of integrated nanostructures.

    SciTech Connect

    Spoerke, Erik David; Bunker, Bruce Conrad; Orendorff, Christopher J.; Bachand, George David; Hendricks, Judy K.; Matzke, Carolyn M.

    2007-01-01

    Microtubules and motor proteins are protein-based biological agents that work cooperatively to facilitate the organization and transport of nanomaterials within living organisms. This report describes the application of these biological agents as tools in a novel, interdisciplinary scheme for assembling integrated nanostructures. Specifically, selective chemistries were used to direct the favorable adsorption of active motor proteins onto lithographically-defined gold electrodes. Taking advantage of the specific affinity these motor proteins have for microtubules, the motor proteins were used to capture polymerized microtubules out of suspension to form dense patterns of microtubules and microtubule bridges between gold electrodes. These microtubules were then used as biofunctionalized templates to direct the organization of functionalized nanocargo including single-walled carbon nanotubes and gold nanoparticles. This biologically-mediated scheme for nanomaterials assembly has shown excellent promise as a foundation for developing new biohybrid approaches to nanoscale manufacturing.

  10. Restricting 32-128 km horizontal scales hardly affects the MJO in the Superparameterized Community Atmosphere Model v.3.0 but the number of cloud-resolving grid columns constrains vertical mixing

    NASA Astrophysics Data System (ADS)

    Pritchard, Michael S.; Bretherton, Christopher S.; DeMott, Charlotte A.

    2014-09-01

    The effects of artificially restricting the 32-128 km horizontal scale regime on MJO dynamics in the Superparameterized Community Atmosphere Model v.3.0 have been explored through reducing the extent of its embedded cloud resolving model (CRM) arrays. Two and four-fold reductions in CRM extent (from 128 to 64 km and 32 km) produce statistical composite MJO signatures with spatial scale, zonal phase speed, and intrinsic wind-convection anomaly structure that are all remarkably similar to the standard SPCAM's MJO. This suggests that the physics of mesoscale convective organization on 32-128 km scales are not critical to MJO dynamics in SPCAM and that reducing CRM extent may be a viable strategy for 400% more computationally efficient analysis of superparameterized MJO dynamics. However several unexpected basic state responses caution that extreme CRM domain reduction can lead to systematic mean state issues in superparameterized models. We hypothesize that an artificial limit on the efficiency of vertical updraft mixing is set by the number of grid columns available for compensating subsidence in the embedded CRM arrays. This can lead to reduced moisture ventilation supporting too much liquid cloud and thus an overly strong cloud shortwave radiative forcing, particularly in regions of deep convection.

  11. Free-Hand Small-Scale Maps: Activities for Cognitive Mapping.

    ERIC Educational Resources Information Center

    Saveland, Robert N.

    1978-01-01

    Suggests that small-scale mapping activities can be used in geography courses to help students understand geographic concepts such as latitude, longitude, situation, relative location, and national boundaries. (Author/DB)

  12. Nitrogen-doped Ge3Te2 materials with self-restricted active region for low power phase-change memory

    NASA Astrophysics Data System (ADS)

    Peng, Cheng; Yang, Pingxiong; Wu, Liangcai; Song, Zhitang; Rao, Feng; Song, Sannian; Zhou, Dong; Chu, Junhao

    2013-01-01

    In this paper, nitrogen-doped Ge3Te2 materials have been investigated for low power phase-change memory. Nitrogen incorporated in Ge3Te2 increases the crystallization temperature, electrical resistance, and band gap significantly. The introduced GeNx pile up at the grain-boundaries and suppress the crystal growth of Ge3Te2, which further leads to larger crystalline resistance and smaller active region. 10-year data retention of nitrogen-doped Ge3Te2 film reaches a peak value with a N2 flow of 2 sccm, while it decreases sharply as the N2 flow reaches 3 sccm. This is due to the formation of inhomogeneous nucleation sites at the GeNx-GeTe interface. Phase-change memory device based on nitrogen-doped Ge3Te2 film shows much lower RESET power consumption than that of pure Ge3Te2. It's considered that the self-restricted active region and effect of GeNx microheaters play an important role in cutting down the power consumption.

  13. Decreased systemic IGF-1 in response to calorie restriction modulates murine tumor cell growth, nuclear factor-κB activation, and inflammation-related gene expression.

    PubMed

    Harvey, Alison E; Lashinger, Laura M; Otto, Glen; Nunez, Nomeli P; Hursting, Stephen D

    2013-12-01

    Calorie restriction (CR) prevents obesity and has potent anticancer effects associated with altered hormones and cytokines. We tested the hypothesis that CR inhibits MC38 mouse colon tumor cell growth through modulation of hormone-stimulated nuclear factor (NF)-κB activation and protumorigenic gene expression. Female C57BL/6 mice were randomized (n = 30/group) to receive control diet or 30% CR diet. At 20 wk, 15 mice/group were killed for body composition analysis. At 21 wk, serum was obtained for hormone analysis. At 22 wk, mice were injected with MC38 cells; tumor growth was monitored for 24 d. Gene expression in excised tumors and MC38 cells was analyzed using real-time RT-PCR. In vitro MC38 NF-κB activation (by p65 ELISA and immunofluorescence) were measured in response to varying IGF-1 concentrations (1-400 ng/mL). Relative to controls, CR mice had decreased tumor volume, body weight, body fat, serum IGF-1, serum leptin, and serum insulin, and increased serum adiponectin (P < 0.05, each). Tumors from CR mice, versus controls, had downregulated inflammation- and/or cancer-related gene expression, including interleukin (IL)-6, IL-1β, tumor necrosis factor-α, cyclooxygenase-2, chemokine (C-C motif) ligand-2, S100A9, and F4/80, and upregulated 15-hydroxyprostaglandin dehydrogenase expression. In MC38 cells in vitro, IGF-1 increased NF-κB activation and NF-κB downstream gene expression (P < 0.05, each). We conclude that CR, in association with reduced systemic IGF-1, modulates MC38 tumor growth, NF-κB activation, and inflammation-related gene expression. Thus, IGF-1 and/or NF-κB inhibition may pharmacologically mimic the anticancer effects of CR to break the obesity-colon cancer link. PMID:22778026

  14. Active osmotic exchanger for advanced filtration at the nano scale

    NASA Astrophysics Data System (ADS)

    Marbach, Sophie; Bocquet, Lyderic

    2015-11-01

    One of the main functions of the kidney is to remove the waste products of an organism, mostly by excreting concentrated urea while reabsorbing water and other molecules. The human kidney is capable of recycling about 200 liters of water per day, at the relatively low cost of 0.5 kJ/L (standard dialysis requiring at least 150 kJ/L). Kidneys are constituted of millions of parallel filtration networks called nephrons. The nephrons of all mammalian kidneys present a specific loop geometry, the Loop of Henle, that is believed to play a key role in the urinary concentrating mechanism. One limb of the loop is permeable to water and the other contains sodium pumps that exchange with a common interstitium. In this work, we take inspiration from this osmotic exchanger design to propose new nanofiltration principles. We first establish simple analytical results to derive general operating principles, based on coupled water permeable pores and osmotic pumps. The best filtration geometry, in terms of power required for a given water recycling ratio, is comparable in many ways to the mammalian nephron. It is not only more efficient than traditional reverse osmosis systems, but can also work at much smaller pressures (of the order of the blood pressure, 0.13 bar, as compared to more than 30 bars for pressure-retarded osmosis systems). We anticipate that our proof of principle will be a starting point for the development of new filtration systems relying on the active osmotic exchanger principle.

  15. Modelling large scale human activity in San Francisco

    NASA Astrophysics Data System (ADS)

    Gonzalez, Marta

    2010-03-01

    Diverse group of people with a wide variety of schedules, activities and travel needs compose our cities nowadays. This represents a big challenge for modeling travel behaviors in urban environments; those models are of crucial interest for a wide variety of applications such as traffic forecasting, spreading of viruses, or measuring human exposure to air pollutants. The traditional means to obtain knowledge about travel behavior is limited to surveys on travel journeys. The obtained information is based in questionnaires that are usually costly to implement and with intrinsic limitations to cover large number of individuals and some problems of reliability. Using mobile phone data, we explore the basic characteristics of a model of human travel: The distribution of agents is proportional to the population density of a given region, and each agent has a characteristic trajectory size contain information on frequency of visits to different locations. Additionally we use a complementary data set given by smart subway fare cards offering us information about the exact time of each passenger getting in or getting out of the subway station and the coordinates of it. This allows us to uncover the temporal aspects of the mobility. Since we have the actual time and place of individual's origin and destination we can understand the temporal patterns in each visited location with further details. Integrating two described data set we provide a dynamical model of human travels that incorporates different aspects observed empirically.

  16. APOBECs and Virus Restriction

    PubMed Central

    Harris, Reuben S.; Dudley, Jaquelin P.

    2015-01-01

    The APOBEC family of single-stranded DNA cytosine deaminases comprises a formidable arm of the vertebrate innate immune system. Pre-vertebrates express a single APOBEC, whereas some mammals produce as many as eleven enzymes. The APOBEC3 subfamily displays both copy number variation and polymorphisms, consistent with ongoing pathogenic pressures. These enzymes restrict the replication of many DNA-based parasites, such as exogenous viruses and endogenous transposable elements. APOBEC1 and activation-induced cytosine deaminase (AID) have specialized functions in RNA editing and antibody gene diversification, respectively, whereas APOBEC2 and APOBEC4 appear to have different functions. Nevertheless, the APOBEC family protects against both periodic viral zoonoses as well as exogenous and endogenous parasite replication. This review highlights viral pathogens that are restricted by APOBEC enzymes, but manage to escape through unique mechanisms. The sensitivity of viruses that lack counterdefense measures highlights the need to develop APOBEC-enabling small molecules as a new class of anti-viral drugs. PMID:25818029

  17. Scale

    ERIC Educational Resources Information Center

    Schaffhauser, Dian

    2009-01-01

    The common approach to scaling, according to Christopher Dede, a professor of learning technologies at the Harvard Graduate School of Education, is to jump in and say, "Let's go out and find more money, recruit more participants, hire more people. Let's just keep doing the same thing, bigger and bigger." That, he observes, "tends to fail, and fail…

  18. Multistability in Large Scale Models of Brain Activity

    PubMed Central

    Golos, Mathieu; Jirsa, Viktor; Daucé, Emmanuel

    2015-01-01

    Noise driven exploration of a brain network’s dynamic repertoire has been hypothesized to be causally involved in cognitive function, aging and neurodegeneration. The dynamic repertoire crucially depends on the network’s capacity to store patterns, as well as their stability. Here we systematically explore the capacity of networks derived from human connectomes to store attractor states, as well as various network mechanisms to control the brain’s dynamic repertoire. Using a deterministic graded response Hopfield model with connectome-based interactions, we reconstruct the system’s attractor space through a uniform sampling of the initial conditions. Large fixed-point attractor sets are obtained in the low temperature condition, with a bigger number of attractors than ever reported so far. Different variants of the initial model, including (i) a uniform activation threshold or (ii) a global negative feedback, produce a similarly robust multistability in a limited parameter range. A numerical analysis of the distribution of the attractors identifies spatially-segregated components, with a centro-medial core and several well-delineated regional patches. Those different modes share similarity with the fMRI independent components observed in the “resting state” condition. We demonstrate non-stationary behavior in noise-driven generalizations of the models, with different meta-stable attractors visited along the same time course. Only the model with a global dynamic density control is found to display robust and long-lasting non-stationarity with no tendency toward either overactivity or extinction. The best fit with empirical signals is observed at the edge of multistability, a parameter region that also corresponds to the highest entropy of the attractors. PMID:26709852

  19. Multistability in Large Scale Models of Brain Activity.

    PubMed

    Golos, Mathieu; Jirsa, Viktor; Daucé, Emmanuel

    2015-12-01

    Noise driven exploration of a brain network's dynamic repertoire has been hypothesized to be causally involved in cognitive function, aging and neurodegeneration. The dynamic repertoire crucially depends on the network's capacity to store patterns, as well as their stability. Here we systematically explore the capacity of networks derived from human connectomes to store attractor states, as well as various network mechanisms to control the brain's dynamic repertoire. Using a deterministic graded response Hopfield model with connectome-based interactions, we reconstruct the system's attractor space through a uniform sampling of the initial conditions. Large fixed-point attractor sets are obtained in the low temperature condition, with a bigger number of attractors than ever reported so far. Different variants of the initial model, including (i) a uniform activation threshold or (ii) a global negative feedback, produce a similarly robust multistability in a limited parameter range. A numerical analysis of the distribution of the attractors identifies spatially-segregated components, with a centro-medial core and several well-delineated regional patches. Those different modes share similarity with the fMRI independent components observed in the "resting state" condition. We demonstrate non-stationary behavior in noise-driven generalizations of the models, with different meta-stable attractors visited along the same time course. Only the model with a global dynamic density control is found to display robust and long-lasting non-stationarity with no tendency toward either overactivity or extinction. The best fit with empirical signals is observed at the edge of multistability, a parameter region that also corresponds to the highest entropy of the attractors. PMID:26709852

  20. Centennial Scale Variations in Lake Productivity Linked to Solar Activity

    NASA Astrophysics Data System (ADS)

    Englebrecht, A.; Bhattacharyya, S.; Guilderson, T. P.; Ingram, L.; Byrne, R.

    2012-12-01

    Solar variations on both decadal and centennial timescales have been associated with climate phenomena (van Loon et al., 2004; Hodell et al., 2001; White et al., 1997). The energy received by the Earth at the peak of the solar cycle increases by <0.1%; so the question has remained of how this could be amplified to produce an observable climate response. Recent modeling shows that the response of the Earth's climate system to the 11-year solar cycle may be amplified through stratosphere and ocean feedbacks and has the potential to impact climate variability on a multidecadal to centennial timescales (Meehl et al., 2009). Here, we report a 1000-year record of changes in the stratigraphy and carbon isotope composition of varved lake sediment from Isla Isabela (22°N, 106°W) in the subtropical northeast Pacific. Stable carbon isotopes and carbonate stratigraphy can be used to infer surface productivity in the lake. Our analysis shows variations in primary productivity on centennial timescales and suggests that solar activity may be an important component of Pacific climate variability. A possible response during solar maxima acts to keep the eastern equatorial Pacific cooler and drier than usual, producing conditions similar to a La Niña event. In the region around Isla Isabela peak solar years were characterized by decreased surface temperatures and suppressed precipitation (Meehl et al., 2009), which enhance productivity at Isabela (Kienel et al. 2011). In the future, we plan to analyze the data using advanced time series analysis techniques like the wavelets together with techniques to handle irregularly spaced time series data. This work performed under the auspices of the U.S. Department of Energy by Lawrence Livermore National Laboratory under Contract DE-AC52-07NA27344. LLNL-ABS-571672

  1. Associations between chronic conditions, body functions, activity limitations and participation restrictions: a cross-sectional approach in Spanish non-clinical populations

    PubMed Central

    Rodríguez-Blázquez, Carmen; Damián, Javier; Andrés-Prado, María José; Almazán-Isla, Javier; Alcalde-Cabero, Enrique; Forjaz, Maria João; Castellote, Juan Manuel; González-Enríquez, Jesús; Martínez-Martín, Pablo; Comín, Magdalena; de Pedro-Cuesta, Jesús

    2016-01-01

    Objectives To analyse the relationships between chronic conditions, body functions, activity limitations and participation restrictions in the International Classification of Functioning, Disability and Health (ICF) framework. Design A cross-sectional study. Setting 2 geographical areas in the Autonomous Region of Aragon, Spain, namely, a rural area, Cinco Villas, and an urban area in the city of Zaragoza. Participants 864 individuals selected by simple random sampling from the register of Social Security card holders, aged 50 years and over, positive to disability screening. Main outcome measures ICF Checklist—body function domains, WHO Disability Assessment Schedule 2.0 (WHODAS 2.0, 36-item (WHODAS-36)) global scores and medical diagnoses (chronic conditions) from primary care records. Results Mild disability (WHODAS-36 level 5–24%) was present in 51.5% of the sample. In the adjusted ordinal regression model with WHODAS-36 as the dependent variable, disability was substantially associated with moderate-to-complete impairment in the following functions: mental, OR 212.8 (95% CI 72 to 628.9); neuromusculoskeletal, OR 44.8 (24.2 to 82.8); and sensory and pain, OR 6.3 (3.5 to 11.2). In the relationship between health conditions and body function impairments, the strongest links were seen for: dementia with mental functions, OR 50.6 (25.1 to 102.1); cerebrovascular disease with neuromusculoskeletal function, OR 5.8 (3.5 to 9.7); and chronic renal failure with sensory function and pain, OR 3.0 (1.49 to 6.4). Dementia, OR 8.1 (4.4 to 14.7) and cerebrovascular disease, OR 4.1 (2.7 to 6.4) were associated with WHODAS-36 scores. Conclusions Body functions are heterogeneously linked to limitations in activities and restrictions on participation, with the highest impact being due to mental and musculoskeletal functions. This may be relevant for disability assessment and intervention design, particularly if defined on a body function basis. Control of specific health

  2. Constitutive activation of Epstein-Barr virus (EBV) nuclear antigen 1 gene transcription by IRF1 and IRF2 during restricted EBV latency.

    PubMed Central

    Schaefer, B C; Paulson, E; Strominger, J L; Speck, S H

    1997-01-01

    The Epstein-Barr virus (EBV) EBNA1 gene promoter active in the type I program of restricted viral latency was recently identified and shown to reside in the viral BamHI Q fragment. This promoter, Qp, is active in a wide variety of cell lines and has an architecture reminiscent of eukaryotic housekeeping gene promoters (B. C. Schaefer, J. L. Strominger, and S. H. Speck, Proc. Natl. Acad. Sci. USA 92:10565-10569, 1995; B. C. Schaefer, J. L. Strominger, and S. H. Speck, Mol. Cell. Biol. 17:364-377, 1997). Here we demonstrate by deletion analysis that the important cis-acting elements regulating Qp are clustered in a relatively small region (ca. 80 bp) surrounding the site of transcription initiation. Immediately upstream of the site of initiation is a region which is protected from DNase I digestion by crude nuclear extracts. Electrophoretic mobility shift analyses (EMSA) employing probes spanning this region demonstrated the presence of two major protein complexes. Deletion analysis of Qp demonstrated that at least one of these complexes plays an important role in Qp activity. Evidence that interferon response factor 2 (IRF2) is a major constituent of the most prominent EMSA complex and that IRF1 may be a minor component of this complex is presented. Transfections into IRF1-/-, IRF2-/-, and IRF1,2-/- fibroblasts demonstrated that absence of both IRF1 and IRF2 reduced Qp activity to approximately the same extent as mutation of the IRF-binding site in Qp, strongly implicating IRF2, and perhaps IRF1, in the regulation of Qp activity. Notably, transcription from Qp was not inducible by either alpha or gamma interferon in EBV-negative B cells but rather was shown to be constitutively activated by IRF1 and IRF2. This observation suggests that IRF1 and IRF2 have a previously unrecognized role as constitutive activators of specific genes. Additionally, data presented indicate that a protein complex containing the nonhistone architectural protein HMG-I(Y) binds to the region

  3. [Can solar/geomagnetic activity restrict the occurrence of some shellfish poisoning outbreaks? The example of PSP caused by Gymnodinium catenatum at the Atlantic Portuguese coast].

    PubMed

    Vale, P

    2013-01-01

    Cyclic outbreaks of accumulation of paralytic shellfish poisoning (PSP) toxins in mussels attributed to Gymnodinium catenatum blooms displayed several of the highest inter-annual maxima coincidental with minima of the 11-year solar sunspot number (SSN) cycle. The monthly distribution of PSP was associated with low levels of the solar radio flux, a more quantitative approach than SSN for fluctuations in solar activity. A comparison between monthly distribution of PSP and other common biotoxins (okadaic acid (OA), dinophysistoxin-2 (DTX2) and amnesic shellfish poisoning (ASP) toxins) demonstrated that only PSP was significantly associated with low levels of radio flux (p < 0.01). PSP occurrence suggests a prior decline in solar activity could be required to act as a trigger, in a similar manner to a photoperiodic signal. The seasonal frequency increased towards autumn during the study period, which might be related to the progressive atmospheric cut-off of deleterious radiation associated with the seasonal change in solar declination, and might play an additional role in seasonal signal-triggering. PSP distribution was also associated with low levels of the geomagnetic index Aa. A comparison between monthly distribution of PSP and other common biotoxins, also demonstrated that only PSP was significantly associated with low levels of the Aa index (p < 0.01). In some years of SSN minima no significant PSP-outbreaks in mussels were detected. This was attributed to a steady rise in geomagnetic activity that could disrupt the triggering signal. Global distribution patterns show that hotspots for G. catenatum blooms are regions with deficient crustal magnetic anomalies. In addition to the variable magnetic field mostly of solar origin, static fields related to magnetized rocks in the crust and upper mantle might play a role in restricting worldwide geographic distribution. PMID:24455892

  4. The structure of the KlcA and ArdB proteins reveals a novel fold and antirestriction activity against Type I DNA restriction systems in vivo but not in vitro

    PubMed Central

    Serfiotis-Mitsa, Dimitra; Herbert, Andrew P.; Roberts, Gareth A.; Soares, Dinesh C.; White, John H.; Blakely, Garry W.; Uhrín, Dušan; Dryden, David T. F.

    2010-01-01

    Plasmids, conjugative transposons and phage frequently encode anti-restriction proteins to enhance their chances of entering a new bacterial host that is highly likely to contain a Type I DNA restriction and modification (RM) system. The RM system usually destroys the invading DNA. Some of the anti-restriction proteins are DNA mimics and bind to the RM enzyme to prevent it binding to DNA. In this article, we characterize ArdB anti-restriction proteins and their close homologues, the KlcA proteins from a range of mobile genetic elements; including an ArdB encoded on a pathogenicity island from uropathogenic Escherichia coli and a KlcA from an IncP-1b plasmid, pBP136 isolated from Bordetella pertussis. We show that all the ArdB and KlcA act as anti-restriction proteins and inhibit the four main families of Type I RM systems in vivo, but fail to block the restriction endonuclease activity of the archetypal Type I RM enzyme, EcoKI, in vitro indicating that the action of ArdB is indirect and very different from that of the DNA mimics. We also present the structure determined by NMR spectroscopy of the pBP136 KlcA protein. The structure shows a novel protein fold and it is clearly not a DNA structural mimic. PMID:20007596

  5. Design, synthesis and biological activity of new neurohypophyseal hormones analogues conformationally restricted in the N-terminal part of the molecule. Highly potent OT receptor antagonists.

    PubMed

    Kwiatkowska, Anna; Ptach, Monika; Borovičková, Lenka; Slaninová, Jiřina; Lammek, Bernard; Prahl, Adam

    2012-08-01

    In this study we present the synthesis and some pharmacological properties of fourteen new analogues of neurohypophyseal hormones conformationally restricted in the N-terminal part of the molecule. All new peptides were substituted at position 2 with cis-1-amino-4-phenylcyclohexane-1-carboxylic acid (cis-Apc). Moreover, one of the new analogues: [cis-Apc(2), Val(4)]AVP was also prepared in N-acylated forms with various bulky acyl groups. All the peptides were tested for pressor, antidiuretic, and in vitro uterotonic activities. We also determined the binding affinity of the selected compounds to human OT receptor. Our results showed that introduction of cis -Apc(2) in position 2 of either AVP or OT resulted in analogues with high antioxytocin potency. Two of the new compounds, [Mpa(1),cis-Apc(2)]AVP and [Mpa(1),cis-Apc(2),Val(4)]AVP, were exceptionally potent antiuterotonic agents (pA(2) = 8.46 and 8.40, respectively) and exhibited higher affinities for the human OT receptor than Atosiban (K (i) values 5.4 and 9.1 nM). Moreover, we have demonstrated for the first time that N -terminal acylation of AVP analogue can improve its selectivity. Using this approach, we obtained compound Aba[cis-Apc(2),Val(4)]AVP (XI) which turned out to be a moderately potent and exceptionally selective OT antagonist (pA(2) = 7.26). PMID:22038179

  6. Immunoreceptor tyrosine-based activation motif phosphorylation during engulfment of Neisseria gonorrhoeae by the neutrophil-restricted CEACAM3 (CD66d) receptor.

    PubMed

    McCaw, Shannon E; Schneider, Jutta; Liao, Edward H; Zimmermann, Wolfgang; Gray-Owen, Scott D

    2003-08-01

    Gonorrhea is characterized by a purulent urethral or cervical discharge consisting primarily of neutrophils associated with Neisseria gonorrhoeae. These interactions are facilitated by gonococcal colony opacity-associated (Opa) protein binding to host cellular CEACAM receptors. Of these, CEACAM3 is restricted to neutrophils and contains an immunoreceptor tyrosine-based activation motif (ITAM) reminiscent of that found within certain phagocytic Fc receptors. CEACAM3 was tyrosine phosphorylated by a Src family kinase-dependent process upon infection by gonococci expressing CEACAM-specific Opa proteins. This phosphorylation was necessary for efficient bacterial uptake; however, a less efficient uptake process became evident when kinase inhibitors or mutagenesis of the ITAM were used to prevent phosphorylation. Ligated CEACAM3 was recruited to a cytoskeleton-containing fraction, intense foci of polymerized actin were evident where bacteria attached to HeLa-CEACAM3, and disruption of polymerized actin by cytochalasin D blocked all bacterial uptake by these cells. These data support a model whereby CEACAM3 can mediate the Opa-dependent uptake of N. gonorrhoeae via either an efficient, ITAM phosphorylation-dependent process that resembles phagocytosis or a less efficient, tyrosine phosphorylation-independent mechanism. PMID:12864848

  7. Cloning and characterization of the 2B4 gene encoding a molecule associated with non-MHC-restricted killing mediated by activated natural killer cells and T cells

    SciTech Connect

    Mathew, P.A.; Garni-Wagner, B.A.; Land, K.; Takashima, A.; Stoneman, E.; Bennett, M.; Kumar, V. )

    1993-11-15

    The authors have recently described a signal transducing molecule, 2B4, expressed on all NK and T cells that mediate non-MHC-restricted killing. The gene encoding this molecule was cloned and its nucleotide sequence determined. The encoded protein of 398 amino acids has a leader peptide of 18 amino acids and a transmembrane region of 24 amino acids. The predicted protein has eight N-linked glycosylation sites, suggesting that it is highly glycosylated. Comparison of 2B4 with sequences in the databanks indicates that 2B4 is a member of the Ig supergene family, and it shows homology to murine and rat CD48 and human LFA-3. Northern blot analysis has shown at least three transcripts for 2B4 in adherent lymphokine-activated killer cells of several mouse strains and TCR-[gamma]/[delta] dendritic epidermal T cell lines but not in allospecific T cell clones. These three mRNA are the products of differential splicing of heterogeneous nuclear RNA. Southern blot analysis of genomic DNA from several mouse strains revealed that 2B4 belongs to a family of closely related genes. The 2B4 gene has been mapped to mouse chromosome 1 by analysis of 2B4 expression in recombinant inbred mouse strains. 48 refs., 6 figs., 2 tabs.

  8. Scaling equations to model variations in operating conditions for activation calculations

    SciTech Connect

    Ho, S.K.

    1994-11-01

    A simple approximate scheme of calculating the variations of fusion activation-induced radioactive inventories with reactor operating conditions (power and time) by scaling equations is formulated. Application of the scheme to evaluate radiological dose-contributing activation products for HT-9 ferritic steel first wall shows decent agreements with numerical results.

  9. Scales of Active Citizenship: New Zealand Teachers' Diverse Perceptions and Practices

    ERIC Educational Resources Information Center

    Wood, Bronwyn Elisabeth

    2012-01-01

    The heightened focus on "active" citizenship in New Zealand's current curriculum (Ministry of Education, 2007) mirrors a pattern observed in many nation's curricula in the past decade. The scale of active citizenship in this curriculum includes an expectation that students will participate in local and national communities but also extends to…

  10. The maximum shortening velocity of muscle should be scaled with activation.

    PubMed

    Chow, J W; Darling, W G

    1999-03-01

    The purpose of this study was to determine whether the maximum shortening velocity (Vmax) in Hill's mechanical model (A. V. Hill. Proc. R. Soc. London Ser. B. 126: 136-195, 1938) should be scaled with activation, measured as a fraction of the maximum isometric force (Fmax). By using the quick-release method, force-velocity (F-V) relationships of the wrist flexors were gathered at five different activation levels (20-100% of maximum at intervals of 20%) from four subjects. The F-V data at different activation levels can be fitted remarkably well with Hill's characteristic equation. In general, the shortening velocity decreases with activation. With the assumption of nonlinear relationships between Hill constants and activation level, a scaled Vmax model was developed. When the F-V curves for submaximal activation were forced to converge at the Vmax obtained with maximum activation (constant Vmax model), there were drastic changes in the shape of the curves. The differences in Vmax values generated by the scaled and constant Vmax models were statistically significant. These results suggest that, when a Hill-type model is used in musculoskeletal modeling, the Vmax should be scaled with activation. PMID:10066719

  11. A Validation and Reliability Study of Community Service Activities Scale in Turkey: A Social Evaluation

    ERIC Educational Resources Information Center

    Demir, Özden; Kaya, Halil Ibrahim; Tasdan, Murat

    2014-01-01

    The purpose of this study is to test the reliability and validity of Community Service Activities Scale (CSAS) developed by Demir, Kaya and Tasdan (2012) with a view to identify perceptions of Faculty of Education students regarding community service activities. The participants of the study are 313 randomly chosen students who attend six…

  12. Low-order chaos in sympathetic nerve activity and scaling of heartbeat intervals

    NASA Astrophysics Data System (ADS)

    Osaka, Motohisa; Kumagai, Hiroo; Sakata, Katsufumi; Onami, Toshiko; Chon, Ki H.; Watanabe, Mari A.; Saruta, Takao

    2003-04-01

    The mechanism of 1/f scaling of heartbeat intervals remains unknown. We recorded heartbeat intervals, sympathetic nerve activity, and blood pressure in conscious rats with normal or high blood pressure. Using nonlinear analyses, we demonstrate that the dynamics of this system of three variables is low-order chaos, and that sympathetic nerve activity leads to heartbeat interval and blood pressure changes. It is suggested that impaired regulation of blood pressure by sympathetic nerve activity is likely to cause experimentally observable steeper scaling of heartbeat intervals in hypertensive (high blood pressure) rats.

  13. The Rasch-built Pompe-specific activity (R-PAct) scale.

    PubMed

    van der Beek, N A M E; Hagemans, M L C; van der Ploeg, A T; van Doorn, P A; Merkies, I S J

    2013-03-01

    We constructed a patient-based interval scale using Rasch analysis, specifically suited to quantify the effects of Pompe disease on patient's ability to carry out daily life activities and their social participation: Rasch-built Pompe-specific Activity scale. Between July 2005 and April 2011, 186 patients aged 16 or older, participated to develop this scale. External construct validity was determined through correlations with the MRC sumscore and Rotterdam Handicap Scale. Furthermore, test-retest reliability was determined in a subgroup of 44 patients. Finally, individual person-level responsiveness was used to determine the proportion of patients demonstrating significant improvement or deterioration during their natural disease course, or during treatment with enzyme replacement therapy. Of the original 49 items, 31 were removed after investigation of model fit, internal reliability, threshold examination, item bias, and local dependency. The remaining 18 items were ordered on a linearly weighted scale and demonstrated good discriminative ability (Person Separation Index 0.96), external construct validity (intraclass correlation coefficient (ICC) for MRC sumscore 0.82, and for the Rotterdam handicap scale 0.86), reliability of person's location (ability comparison: ICC 0.95), and responsiveness. We therefore conclude that the R-PAct scale enables us to accurately detect limitations in activities and social participation throughout the entire disease spectrum in patients with Pompe disease. PMID:23273871

  14. Hypothalamic-pituitary-adrenal activity and pro-opiomelanocortin mRNA levels in the hypothalamus and pituitary of the rat are differentially modulated by acute intermittent morphine with or without water restriction stress.

    PubMed

    Zhou, Y; Spangler, R; Maggos, C E; Wang, X M; Han, J S; Ho, A; Kreek, M J

    1999-11-01

    Acute administration of morphine stimulates the secretion of hypothalamic-pituitary-adrenal (HPA) hormones, ACTH, beta-endorphin and corticosterone in the rat. In this study we investigated the effects of repeated multiple-dose morphine on HPA activity under two different conditions: without or with water restriction stress. Rats received six intermittent injections of morphine (6.25 mg/kg per injection, s.c.) every 2 h and were killed 30 min after the last injection. The results were as follows. (1) Morphine significantly elevated plasma ACTH and corticosterone levels; water restriction also significantly increased ACTH secretion, but with no significant increase of plasma corticosterone levels. In contrast, rats treated with morphine under the water restriction condition failed to show any increases of either ACTH or corticosterone levels. (2) Morphine did not change pro-opiomelanocortin (POMC) mRNA levels in the anterior pituitary; whereas water restriction significantly increased the POMC mRNA levels. The water restriction-induced increases of POMC mRNA in the anterior pituitary were absent in the rats which received morphine. (3) Morphine significantly increased POMC mRNA levels in the hypothalamus; water restriction had no effect. The morphine-induced increases in POMC mRNA in the hypothalamus were absent in the rat under the water restriction condition. These findings, that the effects of morphine on HPA activation or POMC mRNA expression depend on the presence of stress, suggest a counter-regulatory role of opiates on a stress response and opioid gene expression. PMID:10556776

  15. Scales

    ScienceCinema

    Murray Gibson

    2010-01-08

    Musical scales involve notes that, sounded simultaneously (chords), sound good together. The result is the left brain meeting the right brain ? a Pythagorean interval of overlapping notes. This synergy would suggest less difference between the working of the right brain and the left brain than common wisdom would dictate. The pleasing sound of harmony comes when two notes share a common harmonic, meaning that their frequencies are in simple integer ratios, such as 3/2 (G/C) or 5/4 (E/C).

  16. Scales

    SciTech Connect

    Murray Gibson

    2007-04-27

    Musical scales involve notes that, sounded simultaneously (chords), sound good together. The result is the left brain meeting the right brain — a Pythagorean interval of overlapping notes. This synergy would suggest less difference between the working of the right brain and the left brain than common wisdom would dictate. The pleasing sound of harmony comes when two notes share a common harmonic, meaning that their frequencies are in simple integer ratios, such as 3/2 (G/C) or 5/4 (E/C).

  17. Leucine supplementation of a chronically restricted protein and energy diet enhances mTOR pathway activation but not muscle protein synthesis in neonatal pigs.

    PubMed

    Manjarín, Rodrigo; Columbus, Daniel A; Suryawan, Agus; Nguyen, Hanh V; Hernandez-García, Adriana D; Hoang, Nguyet-Minh; Fiorotto, Marta L; Davis, Teresa

    2016-01-01

    Suboptimal nutrient intake represents a limiting factor for growth and long-term survival of low-birth weight infants. The objective of this study was to determine if in neonates who can consume only 70 % of their protein and energy requirements for 8 days, enteral leucine supplementation will upregulate the mammalian target of rapamycin (mTOR) pathway in skeletal muscle, leading to an increase in protein synthesis and muscle anabolism. Nineteen 4-day-old piglets were fed by gastric tube 1 of 3 diets, containing (kg body weight(-1) · day(-1)) 16 g protein and 190 kcal (CON), 10.9 g protein and 132 kcal (R), or 10.8 g protein + 0.2 % leucine and 136 kcal (RL) at 4-h intervals for 8 days. On day 8, plasma AA and insulin levels were measured during 6 post-feeding intervals, and muscle protein synthesis rate and mTOR signaling proteins were determined at 120 min post-feeding. At 120 min, leucine was highest in RL (P < 0.001), whereas insulin, isoleucine and valine were lower in RL and R compared to CON (P < 0.001). Compared to RL and R, the CON diet increased (P < 0.01) body weight, protein synthesis, phosphorylation of S6 kinase (p-S6K1) and 4E-binding protein (p-4EBP1), and activation of eukaryotic initiation factor 4 complex (eIF4E · eIF4G). RL increased (P ≤ 0.01) p-S6K1, p-4EBP1 and eIF4E · eIF4G compared to R. In conclusion, when protein and energy intakes are restricted for 8 days, leucine supplementation increases muscle mTOR activation, but does not improve body weight gain or enhance skeletal muscle protein synthesis in neonatal pigs. PMID:26334346

  18. Synthesis, Protein Levels, Activity and Phosphorylation State of Tyrosine Hydroxylase in Mesoaccumbens and Nigrostriatal Dopamine Pathways of Chronically Food-restricted Rats

    PubMed Central

    Pan, Yan; Berman, Yemiliya; Haberny, Sandra; Meller, Emanuel; Carr, Kenneth D.

    2006-01-01

    Chronic food restriction (FR) enhances the rewarding and motor-activating effects of abused drugs, and is accompanied by changes in dopamine (DA) dynamics and increased D-1 DA receptor-mediated cell signaling and transcriptional responses in nucleus accumbens (NAc). However, little is known about effects of FR on DA synthetic activity in the mesoaccumbens and nigrostriatal pathways. In Experiment 1 of the present study, tyrosine hydroxylase (TH) gene expression was measured in ventral tegmental area and substantia nigra, using real time RT-PCR and in situ hybridization; no differences were observed between FR and ad libitum fed (AL) rats. In Experiment 2, TH protein levels, determined by Western blot, were found to be elevated in NAc and caudate-putamen (CPu) of FR relative to AL rats. In the absence of increased transcription, this may reflect a slowing of TH degradation. In Experiments 3 and 4, DA synthetic activity was assessed by Western blot measurement of TH phosphorylation at Ser-40, and HPLC measurement of in vivo tyrosine hydroxylation rate, as reflected by DOPA accumulation following administration of a decarboxylase inhibitor (NSD-1015; 100 mg/kg, i.p.). Basal phospho-Ser(40)-TH levels did not differ between groups but DOPA accumulation was decreased by FR. Decreased DOPA synthesis, despite increased levels of TH protein, may reflect the inhibitory effect of increased DA binding to TH protein or decreased concentrations of cofactor tetrahydrobiopterin. Finally, in response to d-amphetamine (0.5 and 5.0 mg/kg, i.p.), phospho-Ser(40)-TH was selectively decreased in NAc of FR rats. This suggests increased feedback inhibition of DA synthesis - a possible consequence of postsynaptic receptor hypersensitivity, or increased extracellular DA concentration. These results indicate that FR increases TH protein levels, but may decrease the capacity for DA synthesis by decreasing TH activity. According to this scheme, the previously observed upregulation of striatal

  19. How Large Scale Flows in the Solar Convection Zone may Influence Solar Activity

    NASA Technical Reports Server (NTRS)

    Hathaway, D. H.

    2004-01-01

    Large scale flows within the solar convection zone are the primary drivers of the Sun s magnetic activity cycle. Differential rotation can amplify the magnetic field and convert poloidal fields into toroidal fields. Poleward meridional flow near the surface can carry magnetic flux that reverses the magnetic poles and can convert toroidal fields into poloidal fields. The deeper, equatorward meridional flow can carry magnetic flux toward the equator where it can reconnect with oppositely directed fields in the other hemisphere. These axisymmetric flows are themselves driven by large scale convective motions. The effects of the Sun s rotation on convection produce velocity correlations that can maintain the differential rotation and meridional circulation. These convective motions can influence solar activity themselves by shaping the large-scale magnetic field pattern. While considerable theoretical advances have been made toward understanding these large scale flows, outstanding problems in matching theory to observations still remain.

  20. Telomere Restriction Fragment (TRF) Analysis

    PubMed Central

    Mender, Ilgen; Shay, Jerry W.

    2016-01-01

    While telomerase is expressed in ~90% of primary human tumors, most somatic tissue cells except transiently proliferating stem-like cells do not have detectable telomerase activity (Shay and Wright, 1996; Shay and Wright, 2001). Telomeres progressively shorten with each cell division in normal cells, including proliferating stem-like cells, due to the end replication (lagging strand synthesis) problem and other causes such as oxidative damage, therefore all somatic cells have limited cell proliferation capacity (Hayflick limit) (Hayflick and Moorhead, 1961; Olovnikov, 1973). The progressive telomere shortening eventually leads to growth arrest in normal cells, which is known as replicative senescence (Shay et al., 1991). Once telomerase is activated in cancer cells, telomere length is stabilized by the addition of TTAGGG repeats to the end of chromosomes, thus enabling the limitless continuation of cell division (Shay and Wright, 1996; Shay and Wright, 2001). Therefore, the link between aging and cancer can be partially explained by telomere biology. There are many rapid and convenient methods to study telomere biology such as Telomere Restriction Fragment (TRF), Telomere Repeat Amplification Protocol (TRAP) (Mender and Shay, 2015b) and Telomere dysfunction Induced Foci (TIF) analysis (Mender and Shay, 2015a). In this protocol paper we describe Telomere Restriction Fragment (TRF) analysis to determine average telomeric length of cells. Telomeric length can be indirectly measured by a technique called Telomere Restriction Fragment analysis (TRF). This technique is a modified Southern blot, which measures the heterogeneous range of telomere lengths in a cell population using the length distribution of the terminal restriction fragments (Harley et al., 1990; Ouellette et al., 2000). This method can be used in eukaryotic cells. The description below focuses on the measurement of human cancer cells telomere length. The principle of this method relies on the lack of

  1. Scale-dependent geomorphic responses to active restoration and implications for cutthroat trout

    NASA Astrophysics Data System (ADS)

    Salant, N.; Miller, S. W.

    2009-12-01

    The predominant goal of instream habitat restoration is to increase the diversity, density and/or biomass of aquatic organisms through enhanced physical heterogeneity and increased food availability. In physically homogenized systems, habitat restoration is most commonly achieved at the reach-scale through the addition of structures or channel reconfiguration. Despite the completion of over 6,000 restoration projects in the United States, studies of fish responses to habitat restoration have largely produced equivocal results. Paradoxically, restoration monitoring overwhelmingly focuses on fish response without understanding how these responses link to the physical variables being altered and the scale at which geomorphic changes occur. Our study investigates whether instream habitat restoration affects geomorphic conditions at spatial scales relevant to the organism of interest (i.e. the spatial scale of the variables limiting to that organism). We measure the effects of active restoration on geomorphic metrics at three spatial scales (local, unit, and reach) using a before-after-control-impact design in a historically disturbed and heavily managed cutthroat trout stream. Observed trout habitat preferences (for spawning and juvenile/adult residence) are used to identify the limiting physical variables and are compared to the scale of spatially explicit geomorphic responses. Four reaches representing three different stages of restoration (before, one month and one year after) are surveyed for local-scale physical conditions, unit- and reach-scale morphology, resident fish use, and redd locations. Local-scale physical metrics include depth, nearbed and average velocity, overhead cover, particle size, and water quality metrics. Point measurements stratified by morphological unit are used to determine physical variability among unit types. Habitat complexity and availability are assessed at the reach-scale from topographic surveys and unit maps. Our multi-scale

  2. The temporal structures and functional significance of scale-free brain activity

    PubMed Central

    He, Biyu J.; Zempel, John M.; Snyder, Abraham Z.; Raichle, Marcus E.

    2010-01-01

    SUMMARY Scale-free dynamics, with a power spectrum following P ∝ f-β, are an intrinsic feature of many complex processes in nature. In neural systems, scale-free activity is often neglected in electrophysiological research. Here, we investigate scale-free dynamics in human brain and show that it contains extensive nested frequencies, with the phase of lower frequencies modulating the amplitude of higher frequencies in an upward progression across the frequency spectrum. The functional significance of scale-free brain activity is indicated by task performance modulation and regional variation, with β being larger in default network and visual cortex and smaller in hippocampus and cerebellum. The precise patterns of nested frequencies in the brain differ from other scale-free dynamics in nature, such as earth seismic waves and stock market fluctuations, suggesting system-specific generative mechanisms. Our findings reveal robust temporal structures and behavioral significance of scale-free brain activity and should motivate future study on its physiological mechanisms and cognitive implications. PMID:20471349

  3. The temporal structures and functional significance of scale-free brain activity.

    PubMed

    He, Biyu J; Zempel, John M; Snyder, Abraham Z; Raichle, Marcus E

    2010-05-13

    Scale-free dynamics, with a power spectrum following P proportional to f(-beta), are an intrinsic feature of many complex processes in nature. In neural systems, scale-free activity is often neglected in electrophysiological research. Here, we investigate scale-free dynamics in human brain and show that it contains extensive nested frequencies, with the phase of lower frequencies modulating the amplitude of higher frequencies in an upward progression across the frequency spectrum. The functional significance of scale-free brain activity is indicated by task performance modulation and regional variation, with beta being larger in default network and visual cortex and smaller in hippocampus and cerebellum. The precise patterns of nested frequencies in the brain differ from other scale-free dynamics in nature, such as earth seismic waves and stock market fluctuations, suggesting system-specific generative mechanisms. Our findings reveal robust temporal structures and behavioral significance of scale-free brain activity and should motivate future study on its physiological mechanisms and cognitive implications. PMID:20471349

  4. Connecting multiple spatial scales to decode the population activity of grid cells

    PubMed Central

    Stemmler, Martin; Mathis, Alexander; Herz, Andreas V. M.

    2015-01-01

    Mammalian grid cells fire when an animal crosses the points of an imaginary hexagonal grid tessellating the environment. We show how animals can navigate by reading out a simple population vector of grid cell activity across multiple spatial scales, even though neural activity is intrinsically stochastic. This theory of dead reckoning explains why grid cells are organized into discrete modules within which all cells have the same lattice scale and orientation. The lattice scale changes from module to module and should form a geometric progression with a scale ratio of around 3/2 to minimize the risk of making large-scale errors in spatial localization. Such errors should also occur if intermediate-scale modules are silenced, whereas knocking out the module at the smallest scale will only affect spatial precision. For goal-directed navigation, the allocentric grid cell representation can be readily transformed into the egocentric goal coordinates needed for planning movements. The goal location is set by nonlinear gain fields that act on goal vector cells. This theory predicts neural and behavioral correlates of grid cell readout that transcend the known link between grid cells of the medial entorhinal cortex and place cells of the hippocampus. PMID:26824061

  5. Connecting multiple spatial scales to decode the population activity of grid cells.

    PubMed

    Stemmler, Martin; Mathis, Alexander; Herz, Andreas V M

    2015-12-01

    Mammalian grid cells fire when an animal crosses the points of an imaginary hexagonal grid tessellating the environment. We show how animals can navigate by reading out a simple population vector of grid cell activity across multiple spatial scales, even though neural activity is intrinsically stochastic. This theory of dead reckoning explains why grid cells are organized into discrete modules within which all cells have the same lattice scale and orientation. The lattice scale changes from module to module and should form a geometric progression with a scale ratio of around 3/2 to minimize the risk of making large-scale errors in spatial localization. Such errors should also occur if intermediate-scale modules are silenced, whereas knocking out the module at the smallest scale will only affect spatial precision. For goal-directed navigation, the allocentric grid cell representation can be readily transformed into the egocentric goal coordinates needed for planning movements. The goal location is set by nonlinear gain fields that act on goal vector cells. This theory predicts neural and behavioral correlates of grid cell readout that transcend the known link between grid cells of the medial entorhinal cortex and place cells of the hippocampus. PMID:26824061

  6. Trim9 regulates activity-dependent fine-scale topography in Drosophila.

    PubMed

    Yang, Limin; Li, Ruonan; Kaneko, Takuya; Takle, Kendra; Morikawa, Rei K; Essex, Laura; Wang, Xin; Zhou, Jie; Emoto, Kazuo; Xiang, Yang; Ye, Bing

    2014-05-01

    Topographic projection of afferent terminals into 2D maps in the CNS is a general strategy used by the nervous system to encode the locations of sensory stimuli. In vertebrates, it is known that although guidance cues are critical for establishing a coarse topographic map, neural activity directs fine-scale topography between adjacent afferent terminals [1-4]. However, the molecular mechanism underlying activity-dependent regulation of fine-scale topography is poorly understood. Molecular analysis of the spatial relationship between adjacent afferent terminals requires reliable localization of the presynaptic terminals of single neurons as well as genetic manipulations with single-cell resolution in vivo. Although both requirements can potentially be met in Drosophila melanogaster [5, 6], no activity-dependent topographic system has been identified in flies [7]. Here we report a topographic system that is shaped by neuronal activity in Drosophila. With this system, we found that topographic separation of the presynaptic terminals of adjacent nociceptive neurons requires different levels of Trim9, an evolutionarily conserved signaling molecule [8-11]. Neural activity regulates Trim9 protein levels to direct fine-scale topography of sensory afferents. This study offers both a novel mechanism by which neural activity directs fine-scale topography of axon terminals and a new system to study this process at single-neuron resolution. PMID:24746793

  7. Bone marrow mesenchymal stem cells express a restricted set of functionally active chemokine receptors capable of promoting migration to pancreatic islets.

    PubMed

    Sordi, Valeria; Malosio, Maria Luisa; Marchesi, Federica; Mercalli, Alessia; Melzi, Raffaella; Giordano, Tiziana; Belmonte, Nathalie; Ferrari, Giuliana; Leone, Biagio Eugenio; Bertuzzi, Federico; Zerbini, Gianpaolo; Allavena, Paola; Bonifacio, Ezio; Piemonti, Lorenzo

    2005-07-15

    Bone marrow-derived mesenchymal stem cells (BM-MSCs) are stromal cells with the ability to proliferate and differentiate into many tissues. Although they represent powerful tools for several therapeutic settings, mechanisms regulating their migration to peripheral tissues are still unknown. Here, we report chemokine receptor expression on human BM-MSCs and their role in mediating migration to tissues. A minority of BM-MSCs (2% to 25%) expressed a restricted set of chemokine receptors (CXC receptor 4 [CXCR4], CX3C receptor 1 [CX3CR1], CXCR6, CC chemokine receptor 1 [CCR1], CCR7) and, accordingly, showed appreciable chemotactic migration in response to the chemokines CXC ligand 12 (CXCL12), CX3CL1, CXCL16, CC chemokine ligand 3 (CCL3), and CCL19. Using human pancreatic islets as an in vitro model of peripheral tissue, we showed that islet supernatants released factors able to attract BM-MSCs in vitro, and this attraction was principally mediated by CX3CL1 and CXCL12. Moreover, cells with features of BM-MSCs were detected within the pancreatic islets of mice injected with green fluorescent protein (GFP)-positive BM. A population of bona fide MSCs that also expressed CXCR4, CXCR6, CCR1, and CCR7 could be isolated from normal adult human pancreas. This study defines the chemokine receptor repertoire of human BM-MSCs that determines their migratory activity. Modulation of homing capacity may be instrumental for harnessing the therapeutic potential of BM-MSCs. PMID:15784733

  8. 32 CFR 806.24 - Fee restrictions.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 6 2011-07-01 2011-07-01 false Fee restrictions. 806.24 Section 806.24 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION AIR FORCE FREEDOM OF INFORMATION ACT PROGRAM § 806.24 Fee restrictions. For FOIA purposes, Air Force activities will consider...

  9. 32 CFR 806.24 - Fee restrictions.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 6 2010-07-01 2010-07-01 false Fee restrictions. 806.24 Section 806.24 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION AIR FORCE FREEDOM OF INFORMATION ACT PROGRAM § 806.24 Fee restrictions. For FOIA purposes, Air Force activities will consider...

  10. 32 CFR 806.24 - Fee restrictions.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 32 National Defense 6 2013-07-01 2013-07-01 false Fee restrictions. 806.24 Section 806.24 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION AIR FORCE FREEDOM OF INFORMATION ACT PROGRAM § 806.24 Fee restrictions. For FOIA purposes, Air Force activities will consider...

  11. 32 CFR 806.24 - Fee restrictions.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 32 National Defense 6 2012-07-01 2012-07-01 false Fee restrictions. 806.24 Section 806.24 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION AIR FORCE FREEDOM OF INFORMATION ACT PROGRAM § 806.24 Fee restrictions. For FOIA purposes, Air Force activities will consider...

  12. 32 CFR 806.24 - Fee restrictions.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 32 National Defense 6 2014-07-01 2014-07-01 false Fee restrictions. 806.24 Section 806.24 National Defense Department of Defense (Continued) DEPARTMENT OF THE AIR FORCE ADMINISTRATION AIR FORCE FREEDOM OF INFORMATION ACT PROGRAM § 806.24 Fee restrictions. For FOIA purposes, Air Force activities will consider...

  13. Restricted Interests and Teacher Presentation of Items

    ERIC Educational Resources Information Center

    Stocco, Corey S.; Thompson, Rachel H.; Rodriguez, Nicole M.

    2011-01-01

    Restricted and repetitive behavior (RRB) is more pervasive, prevalent, frequent, and severe in individuals with autism spectrum disorders (ASDs) than in their typical peers. One subtype of RRB is restricted interests in items or activities, which is evident in the manner in which individuals engage with items (e.g., repetitious wheel spinning),…

  14. Development and psychometric testing of the active aging scale for Thai adults

    PubMed Central

    Thanakwang, Kattika; Isaramalai, Sang-arun; Hatthakit, Urai

    2014-01-01

    Background Active aging is central to enhancing the quality of life for older adults, but its conceptualization is not often made explicit for Asian elderly people. Little is known about active aging in older Thai adults, and there has been no development of scales to measure the expression of active aging attributes. Purpose The aim of this study was to develop a culturally relevant composite scale of active aging for Thai adults (AAS-Thai) and to evaluate its reliability and validity. Methods Eight steps of scale development were followed: 1) using focus groups and in-depth interviews, 2) gathering input from existing studies, 3) developing preliminary quantitative measures, 4) reviewing for content validity by an expert panel, 5) conducting cognitive interviews, 6) pilot testing, 7) performing a nationwide survey, and 8) testing psychometric properties. In a nationwide survey, 500 subjects were randomly recruited using a stratified sampling technique. Statistical analyses included exploratory factor analysis, item analysis, and measures of internal consistency, concurrent validity, and test–retest reliability. Results Principal component factor analysis with varimax rotation resulted in a final 36-item scale consisting of seven factors of active aging: 1) being self-reliant, 2) being actively engaged with society, 3) developing spiritual wisdom, 4) building up financial security, 5) maintaining a healthy lifestyle, 6) engaging in active learning, and 7) strengthening family ties to ensure care in later life. These factors explained 69% of the total variance. Cronbach’s alpha coefficient for the overall AAS-Thai was 0.95 and varied between 0.81 and 0.91 for the seven subscales. Concurrent validity and test–retest reliability were confirmed. Conclusion The AAS-Thai demonstrated acceptable overall validity and reliability for measuring the multidimensional attributes of active aging in a Thai context. This newly developed instrument is ready for use as a

  15. Development of scaling factors for the activated concrete of the KRR-2.

    PubMed

    Hong, Sang-Bum; Kang, Mun-Ja; Lee, Ki-Won; Chung, Un-Soo

    2009-01-01

    The biological shielding concrete of KRR-2 was activated by a thermal neutron reaction during the operation of the reactor, thus a variety of radionuclides were generated in the concrete. In order to verify the radioactivity for the final disposal of waste and to achieve a more efficient cutting of the concrete, the radioactivity inventories and distributions of the activated concrete were evaluated. The activity of gamma-emitting radionuclides was measured by using an HPGe detector. The beta-emitting radionuclides were measured by an oxidation/combustion method for (3)H and (14)C and a combined method of an extraction chromatography and a liquid scintillation for (55)Fe and (63)Ni. The dominant radioactive nuclides in the activated concrete were (3)H, (14)C, (55)Fe and (60)Co, and the maximum gamma activity was 105Bq/g at the surface around the thermal column. The specific activities of all the nuclides were found to decrease almost linearly on a logarithmic scale along the depth from the inner surface of the concrete. Equations for scaling factors were obtained by a linear regression of logarithms from the radioactivity data of (3)H/(60)Co, (14)C/(60)Co and (55)Fe/(60)Co nuclide pairs of the activated concrete. The scaling factors can be utilized for the estimation of beta radioactivity without the time consuming separation processes of the nuclides. PMID:19303787

  16. ActivitySim: large-scale agent based activity generation for infrastructure simulation

    SciTech Connect

    Gali, Emmanuel; Eidenbenz, Stephan; Mniszewski, Sue; Cuellar, Leticia; Teuscher, Christof

    2008-01-01

    The United States' Department of Homeland Security aims to model, simulate, and analyze critical infrastructure and their interdependencies across multiple sectors such as electric power, telecommunications, water distribution, transportation, etc. We introduce ActivitySim, an activity simulator for a population of millions of individual agents each characterized by a set of demographic attributes that is based on US census data. ActivitySim generates daily schedules for each agent that consists of a sequence of activities, such as sleeping, shopping, working etc., each being scheduled at a geographic location, such as businesses or private residences that is appropriate for the activity type and for the personal situation of the agent. ActivitySim has been developed as part of a larger effort to understand the interdependencies among national infrastructure networks and their demand profiles that emerge from the different activities of individuals in baseline scenarios as well as emergency scenarios, such as hurricane evacuations. We present the scalable software engineering principles underlying ActivitySim, the socia-technical modeling paradigms that drive the activity generation, and proof-of-principle results for a scenario in the Twin Cities, MN area of 2.6 M agents.

  17. Exogenous progesterone exacerbates running response of adolescent female mice to repeated food restriction stress by changing α4-GABAA receptor activity of hippocampal pyramidal cells.

    PubMed

    Wable, G S; Chen, Y-W; Rashid, S; Aoki, C

    2015-12-01

    Adolescent females are particularly vulnerable to mental illnesses with co-morbidity of anxiety, such as anorexia nervosa (AN). We used an animal model of AN, called activity-based anorexia (ABA), to investigate the neurobiological basis of vulnerability to repeated, food restriction (FR) stress-evoked anxiety. Twenty-one of 23 adolescent female mice responded to the 1st FR with increased wheel-running activity (WRA), even during the limited period of food access, thereby capturing AN's symptoms of voluntary FR and over-exercise. Baseline WRA was an excellent predictor of FR-elicited WRA (severity of ABA, SOA), with high baseline runners responding to FR with minimal SOA (i.e., negative correlation). Nine gained resistance to ABA following the 1st FR. Even though allopregnanolone (3α-OH-5α-pregnan-20-one, THP), the metabolite of progesterone (P4), is a well-recognized anxiolytic agent, subcutaneous P4 to these ABA-resistant animals during the 2nd FR was exacerbative, evoking greater WRA than the counterpart resistant group that received oil vehicle, only. Moreover, P4 had no WRA-reducing effect on animals that remained ABA-vulnerable. To explain the sensitizing effect of P4 upon the resistant mice, we examined the relationship between P4 treatment and levels of the α4 subunit of GABAARs at spines of pyramidal cells of the hippocampal CA1, a parameter previously shown to correlate with resistance to ABA. α4 levels at spine membrane correlated strongly and negatively with SOA during the 1st ABA (prior to P4 injection), confirming previous findings. α4 levels were greater among P4-treated animals that had gained resistance than of vehicle-treated resistant animals or of the vulnerable animals with or without P4. We propose that α4-GABAARs play a protective role by counterbalancing the ABA-induced increase in excitability of CA1 pyramidal neurons, and although exogenous P4's metabolite, THP, enhances α4 expression, especially among those that can gain resistance

  18. BrainModes: a principled approach to modeling and measuring large-scale neuronal activity.

    PubMed

    Breakspear, Michael J; Daffertshofer, Andreas; Ritter, Petra

    2009-09-30

    Complex systems, such as the brain, exhibit multiple levels of organization due to processes which support the separation of scales across time and/or space. That is, cooperative phenomena--or "modes" of activity--occurring at one scale give rise to coherent spatiotemporal structures at a coarser scale. In turn, structures at the coarser scale constrain--and hence influence--emerging activity at a finer scale. BrainModes is an annual scientific summit which seeks to bring together experimental, computational and theoretical neuroscientists engaged at different levels of organization, with the goal of advancing a principled approach to understanding brain function based on the concept of cooperative phenomena in complex systems. Phenomena of particular interest include synchronization, stochastic influences, and spatiotemporal processes in both healthy and pathological states such as seizures. This Special Issue reports the 2008 BrainModes Workshop, held in Amsterdam (December 2008) which focused on the application of this framework to the analysis of brain oscillations and synchronization phenomena across time scales. PMID:19607859

  19. EVALUATION OF FULL SCALE ACTIVATED SLUDGE SYSTEMS UTILIZING POWDERED ACTIVATED CARBON ADDITION WITH WET AIR REGENERATION

    EPA Science Inventory

    The addition of powdered activated carbon (PAC) to activated sludge systems is a proven method of wastewater treatment. Of eleven POTWs in the U.S. that were designed for PAC use, ten included wet air regeneration (WAR) for the destruction of secondary sludge solids and recovery ...

  20. Scaling laws of coronal loops compared to a 3D MHD model of an active region

    NASA Astrophysics Data System (ADS)

    Bourdin, Ph.-A.; Bingert, S.; Peter, H.

    2016-04-01

    Context. The structure and heating of coronal loops have been investigated for decades. Established scaling laws relate fundamental quantities like the loop apex temperature, pressure, length, and coronal heating. Aims: We test these scaling laws against a large-scale 3D magneto-hydrodynamics (MHD) model of the solar corona, which became feasible with current high-performance computing. Methods: We drove an active region simulation with photospheric observations and find strong similarities to the observed coronal loops in X-rays and extreme-ultraviolet (EUV) wavelength. A 3D reconstruction of stereoscopic observations shows that our model loops have a realistic spatial structure. We compared scaling laws to our model data extracted along an ensemble of field lines. Finally, we fit a new scaling law that represents hot loops and also cooler structures, which was not possible before based only on observations. Results: Our model data gives some support for scaling laws that were established for hot and EUV-emissive coronal loops. For the Rosner-Tucker-Vaiana (RTV) scaling law we find an offset to our model data, which can be explained by 1D considerations of a static loop with a constant heat input and conduction. With a fit to our model data we set up a new scaling law for the coronal heat input along magnetic field lines. Conclusions: RTV-like scaling laws were fitted to hot loops and therefore do not predict well the coronal heat input for cooler structures that are barely observable. The basic differences between 1D and self-consistent 3D modeling account for deviations between earlier scaling laws and ours. We also conclude that a heating mechanism by MHD-turbulent dissipation within a braided flux tube would heat the corona stronger than is consistent with our model corona.

  1. Summary of pilot-scale activities with resorcinol ion exchange resin

    SciTech Connect

    Cicero, C.A.; Bickford, D.F.; Sargent, T.N.; Andrews, M.K.; Bibler, J.P.; Bibler, N.E.; Jantzen, C.M.

    1995-10-02

    The Mixed Waste Focus Area (MWFA) of the Department of Energy (DOE) is currently investigating vitrification technology for treatment of low level mixed wastes (LLMW). They have chartered the Savannah River Technology Center (SRTC) to study vitrification of the wastes through an Office of Technology Development (OTD) Technical Task Plan (TTP). SRTC`s efforts have included crucible-scale studies and pilot scale testing on simulated LLMW sludges, resins, soils, and other solid wastes. Results from the crucible-scale studies have been used as the basis for the pilot-scale demonstrations. As part of the fiscal year (FY) 1995 activities, SRTC performed crucible-scale studies with organic resins. This waste stream was selected because of the large number of DOE sites, as well as commercial industries, that use resins for treatment of liquid wastes. Pilot-scale studies were to be completed in FY 1995, but could not be due to a reduction in funding. Instead, a compilation of pilot-scale tests with organic resins performed under the guidance of SRTC was provided in this report. The studies which will be discussed used a resorcinol- formaldehyde resin loaded with non-radioactive cesium, which was fed with simulated wastewater treatment sludge feed. The first study was performed at the SRTC in the mini-melter, 1/100th scale of the Defense Waste Processing Facility (DWPF) melter, and also involved limited crucible-scale studies to determine the resin loading obtainable. The other study was performed at the DOE/Industrial Center for Vitrification Research (Center) and involved both crucible and pilot-scale testing in the Stir-Melter stirred-melter. Both studies were successful in vitrifying the resin in simulated radioactive sludge and glass additive feeds.

  2. Plant chlorophyll fluorescence: active and passive measurements at canopy and leaf scales with different nitrogen treatments

    PubMed Central

    Cendrero-Mateo, M. Pilar; Moran, M. Susan; Papuga, Shirley A.; Thorp, K.R.; Alonso, L.; Moreno, J.; Ponce-Campos, G.; Rascher, U.; Wang, G.

    2016-01-01

    Most studies assessing chlorophyll fluorescence (ChlF) have examined leaf responses to environmental stress conditions using active techniques. Alternatively, passive techniques are able to measure ChlF at both leaf and canopy scales. However, the measurement principles of both techniques are different, and only a few datasets concerning the relationships between them are reported in the literature. In this study, we investigated the potential for interchanging ChlF measurements using active techniques with passive measurements at different temporal and spatial scales. The ultimate objective was to determine the limits within which active and passive techniques are comparable. The results presented in this study showed that active and passive measurements were highly correlated over the growing season across nitrogen treatments at both canopy and leaf-average scale. At the single-leaf scale, the seasonal relation between techniques was weaker, but still significant. The variability within single-leaf measurements was largely related to leaf heterogeneity associated with variations in CO2 assimilation and stomatal conductance, and less so to variations in leaf chlorophyll content, leaf size or measurement inputs (e.g. light reflected and emitted by the leaf and illumination conditions and leaf spectrum). This uncertainty was exacerbated when single-leaf analysis was limited to a particular day rather than the entire season. We concluded that daily measurements of active and passive ChlF at the single-leaf scale are not comparable. However, canopy and leaf-average active measurements can be used to better understand the daily and seasonal behaviour of passive ChlF measurements. In turn, this can be used to better estimate plant photosynthetic capacity and therefore to provide improved information for crop management. PMID:26482242

  3. Plant chlorophyll fluorescence: active and passive measurements at canopy and leaf scales with different nitrogen treatments.

    PubMed

    Cendrero-Mateo, M Pilar; Moran, M Susan; Papuga, Shirley A; Thorp, K R; Alonso, L; Moreno, J; Ponce-Campos, G; Rascher, U; Wang, G

    2016-01-01

    Most studies assessing chlorophyll fluorescence (ChlF) have examined leaf responses to environmental stress conditions using active techniques. Alternatively, passive techniques are able to measure ChlF at both leaf and canopy scales. However, the measurement principles of both techniques are different, and only a few datasets concerning the relationships between them are reported in the literature. In this study, we investigated the potential for interchanging ChlF measurements using active techniques with passive measurements at different temporal and spatial scales. The ultimate objective was to determine the limits within which active and passive techniques are comparable. The results presented in this study showed that active and passive measurements were highly correlated over the growing season across nitrogen treatments at both canopy and leaf-average scale. At the single-leaf scale, the seasonal relation between techniques was weaker, but still significant. The variability within single-leaf measurements was largely related to leaf heterogeneity associated with variations in CO2 assimilation and stomatal conductance, and less so to variations in leaf chlorophyll content, leaf size or measurement inputs (e.g. light reflected and emitted by the leaf and illumination conditions and leaf spectrum). This uncertainty was exacerbated when single-leaf analysis was limited to a particular day rather than the entire season. We concluded that daily measurements of active and passive ChlF at the single-leaf scale are not comparable. However, canopy and leaf-average active measurements can be used to better understand the daily and seasonal behaviour of passive ChlF measurements. In turn, this can be used to better estimate plant photosynthetic capacity and therefore to provide improved information for crop management. PMID:26482242

  4. Chronic, Wireless Recordings of Large Scale Brain Activity in Freely Moving Rhesus Monkeys

    PubMed Central

    Schwarz, David A.; Lebedev, Mikhail A.; Hanson, Timothy L.; Dimitrov, Dragan F.; Lehew, Gary; Meloy, Jim; Rajangam, Sankaranarayani; Subramanian, Vivek; Ifft, Peter J.; Li, Zheng; Ramakrishnan, Arjun; Tate, Andrew; Zhuang, Katie; Nicolelis, Miguel A.L.

    2014-01-01

    Advances in techniques for recording large-scale brain activity contribute to both the elucidation of neurophysiological principles and the development of brain-machine interfaces (BMIs). Here we describe a neurophysiological paradigm for performing tethered and wireless large-scale recordings based on movable volumetric three-dimensional (3D) multielectrode implants. This approach allowed us to isolate up to 1,800 units per animal and simultaneously record the extracellular activity of close to 500 cortical neurons, distributed across multiple cortical areas, in freely behaving rhesus monkeys. The method is expandable, in principle, to thousands of simultaneously recorded channels. It also allows increased recording longevity (5 consecutive years), and recording of a broad range of behaviors, e.g. social interactions, and BMI paradigms in freely moving primates. We propose that wireless large-scale recordings could have a profound impact on basic primate neurophysiology research, while providing a framework for the development and testing of clinically relevant neuroprostheses. PMID:24776634

  5. Individual differences in FFA activity suggest independent processing at different spatial scales.

    PubMed

    Gauthier, Isabel; Curby, Kim M; Skudlarski, Pawel; Epstein, Russell A

    2005-06-01

    The brain processes images at different spatial scales, but it is unclear how far into the visual stream different scales remain segregated. Using functional magnetic resonance imaging, we found evidence that BOLD activity in the fusiform face area (FFA) reflects computations based on separate spatial frequency inputs. When subjects perform different tasks (attend location vs. identity; attend whole vs. parts) or the same task with different stimuli (upright or inverted) with high- and low-pass images of cars and faces, individual differences in the FFA in one condition are correlated with those in the other condition. However, FFA activity in response to low-pass stimuli is independent of its response to high-pass stimuli. These results suggest that spatial scales are not integrated before the FFA and that processing in this area could support the flexible use of different sources of information present in broad-pass images. PMID:16180628

  6. Reconstructing the Rasch-Built Myotonic Dystrophy Type 1 Activity and Participation Scale

    PubMed Central

    Hermans, Mieke C. E.; Hoeijmakers, Janneke G. J.; Faber, Catharina G.; Merkies, Ingemar S. J.

    2015-01-01

    Introduction A previously published Rasch-built activity and participation scale specifically designed for patients with myotonic dystrophy type 1 (DM1) was criticized for having been constructed in a relatively small cohort of patients and containing items too broadly phrased for DM1 patients, thus hampering its clinical use. Methods We report the results of the reconstructed Rasch-built DM1 activity and participation scale for clinical use (DM1-ActivC) through Rasch analyses using an expanded questionnaire containing 146 more simply phrased activity and participation inquiries completed by 340 patients with DM1. Results Through stepwise investigation including data quality control, model fit, response category ordering, local dependency and item bias, we succeeded in reconstructing the DM1-ActivC consisting of 25 items that showed good Rasch model fit, including construct convergent validity, items’ weights and persons’ locations reliability, and unidimensionality. Conclusion The DM1-ActivC scale has been reconstructed and fulfills all modern clinimetric requirements. Its use is recommended in future longitudinal trials in patients with DM1 to determine its responsiveness. PMID:26484877

  7. Evaluation of Social Cognitive Scaling Response Options in the Physical Activity Domain

    ERIC Educational Resources Information Center

    Rhodes, Ryan E.; Matheson, Deborah Hunt; Mark, Rachel

    2010-01-01

    The purpose of this study was to compare the reliability, variability, and predictive validity of two common scaling response formats (semantic differential, Likert-type) and two numbers of response options (5-point, 7-point) in the physical activity domain. Constructs of the theory of planned behavior were chosen in this analysis based on its…

  8. FULL-SCALE DEMONSTRATION OF OPEN TANK OXYGEN ACTIVATED SLUDGE TREATMENT

    EPA Science Inventory

    This report presents an operating summary of a full-scale demonstration of the FMC open tank pure oxygen (FMC O2) activated sludge system, conducted at the facilities of the Metropolitan Denver Sewage Disposal District No. 1 (Metro) in Denver, Colorado. The system was operated ov...

  9. Psychometric Evaluation of the Physical Activity Enjoyment Scale in Adults with Functional Limitations.

    PubMed

    Murrock, Carolyn J; Bekhet, Abir; Zauszniewski, Jaclene A

    2016-01-01

    Enjoyment is an important construct for understanding physical activity participation, and it has not been examined in adults with functional limitations. This secondary analysis reported the reliability and validity of the Physical Activity Enjoyment Scale (PACES) in a convenience sample of 40 adults with functional limitations. The participants completed the PACES, Center for Epidemiological Studies Depression Scale (CES-D), and the Late Life Function and Disability Instrument (LLFDI) prior to beginning a 12-week feasibility dance intervention study. Results indicated reliability as Cronbach's alpha was .95 and mean inter-item correlation was .52. To further support reliability, homogeneity of the instrument was evaluated using item-to-total scale correlations. Homogeneity was supported as all items had corrected item-to-total correlations greater than .30. For validity, the PACES was significantly related to only the Physical Function component of the LLFDI (r = .38, p = .02), but not the CES-D. Exploratory factor analysis revealed a 3-factor structure that accounted for 73.76% of the variance. This feasibility intervention dance study represented the first attempt to examine the psychometric properties of the PACES in adults with functional limitations. The findings demonstrate support for the scale's reliability and validity among adults with functional limitations. Results are informative as further psychometric testing of the PACES is recommended using randomized clinical trials with larger sample sizes. Enjoyment for physical activity is an important construct for understanding physical activity participation in adults with functional limitations. PMID:26980666

  10. Estimates of genetic parameters among scale activity scores, growth, and fatness in pigs

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Genetic parameters for scale activity score were estimated from generations 5, 6, and 7 of a randomly selected, composite population composed of Duroc, Large White, and two sources of Landrace (n = 2,186). At approximately 156 d of age, pigs were weighed (WT) and ultrasound backfat measurements (BF1...

  11. Reliability and Construct Validity of Turkish Version of Physical Education Activities Scale

    ERIC Educational Resources Information Center

    Memis, Ugur Altay

    2013-01-01

    This research was conducted to examine the reliability and construct validity of Turkish version of physical education activities scale (PEAS) which was developed by Thomason (2008). Participants in this study included 313 secondary and high school students from 7th to 11th grades. To analyse the data, confirmatory factor analysis, post hoc…

  12. Genetic Parameter Estimates Among Scale Activity Score and Farrowing Disposition with Reproductive Traits in Swine

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Scale activity score (SA) at 5 months of age ranged from 1 to 5. Farrowing disposition score (FD) ranged from 1 to 3. Reproductive traits included age at puberty (AP), number born alive (NBA), number born dead (NBD), litter birth weight (LBW), average birth weight (ABW), number weaned adjusted for c...

  13. Motivations Underlying Career Decision-Making Activities: The Career Decision-Making Autonomy Scale (CDMAS)

    ERIC Educational Resources Information Center

    Guay, Frederic

    2005-01-01

    The purpose of the present research was to develop and validate a measure of motivation toward career decision-making activities, the Career Decision-Making Autonomy Scale (CDMAS). The CDMAS is designed to assess the constructs of intrinsic motivation, identified regulation, introjected regulation, and external regulation. A longitudinal study was…

  14. CURRENT HELICITY OF ACTIVE REGIONS AS A TRACER OF LARGE-SCALE SOLAR MAGNETIC HELICITY

    SciTech Connect

    Zhang, H.; Gao, Y.; Xu, H.; Moss, D.; Kleeorin, N.; Rogachevskii, I.; Kuzanyan, K.; Sokoloff, D.

    2012-05-20

    We demonstrate that the current helicity observed in solar active regions traces the magnetic helicity of the large-scale dynamo generated field. We use an advanced two-dimensional mean-field dynamo model with dynamo saturation based on the evolution of the magnetic helicity and algebraic quenching. For comparison, we also studied a more basic two-dimensional mean-field dynamo model with simple algebraic alpha-quenching only. Using these numerical models we obtained butterfly diagrams both for the small-scale current helicity and also for the large-scale magnetic helicity, and compared them with the butterfly diagram for the current helicity in active regions obtained from observations. This comparison shows that the current helicity of active regions, as estimated by -A {center_dot} B evaluated at the depth from which the active region arises, resembles the observational data much better than the small-scale current helicity calculated directly from the helicity evolution equation. Here B and A are, respectively, the dynamo generated mean magnetic field and its vector potential. A theoretical interpretation of these results is given.

  15. A Fundamental Study for Efficient Implementaion of Online Collaborative Activities in Large-Scale Classes

    ERIC Educational Resources Information Center

    Matsuba, Ryuichi; Suzuki, Yusei; Kubota, Shin-Ichiro; Miyazaki, Makoto

    2015-01-01

    We study tactics for writing skills development through cross-disciplinary learning in online large-scale classes, and particularly are interested in implementation of online collaborative activities such as peer reviewing of writing. The goal of our study is to carry out collaborative works efficiently via online effectively in large-scale…

  16. Validity and Reliability of a Turkish Version of the Friendship Activity Scale

    ERIC Educational Resources Information Center

    Nalbant, Sibel; Aktop, Abdurrahman; Ozer, Dilara; Hutzler, Yeshayahu

    2011-01-01

    The purpose of this study was to develop a valid and reliable Turkish version of the Friendship Activity Scale (FAS). Both the English and Turkish versions of the FAS were administered to 36 students to check for language equivalence. The Turkish version of the FAS was then administered to 226 students to ensure internal consistency, and to 61…

  17. Dietary restrictions and cancer.

    PubMed Central

    Hart, R W; Turturro, A

    1997-01-01

    Dietary restriction (DR) alters a significant environmental factor in carcinogenesis, dietary intake, thus inhibiting both spontaneous and induced tumorigenesis. Potential mechanisms for the inhibition of spontaneous cancer may include the effects of DR to do the following: decrease body weight, which decreases cellular proliferation and increases apoptosis in a number of organs that increase and decrease with body size; decrease body temperature, thereby lowering the amount of endogenous DNA damage temperature generates; decrease oxidative damage, by increasing antioxidant damage defense systems; decrease, generally, cellular proliferation; and protect the fidelity of the genome by decreasing DNA damage, increasing DNA repair, and preventing aberrant gene expression. Potential mechanisms for reducing induced tumor incidence include lowering agent activation, changing agent disposition, decreasing the adducts most associated with agent toxicity, and inhibiting tumor progression through mechanisms similar to those that can effect spontaneous tumorigenesis. As a method to control a major source of environmental cancer, and as the major modulator of the agent induction of this disease, understanding how DR works may significantly contribute to the efforts to explain how diet impacts on development of cancer in the United States, and may suggest methods to reduce the adverse impacts of other environmental agents on the disease. PMID:9255593

  18. 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. PMID:22059343

  19. Using Rasch modeling to re-evaluate three scales related to physical activity: enjoyment, perceived benefits and perceived barriers.

    PubMed

    Heesch, K C; Mâsse, L C; Dunn, A L

    2006-12-01

    Studies suggest that enjoyment, perceived benefits and perceived barriers may be important mediators of physical activity. However, the psychometric properties of these scales have not been assessed using Rasch modeling. The purpose of this study was to use Rasch modeling to evaluate the properties of three scales commonly used in physical activity studies: the Physical Activity Enjoyment Scale, the Benefits of Physical Activity Scale and the Barriers to Physical Activity Scale. The scales were administered to 378 healthy adults, aged 25-75 years (50% women, 62% Whites), at the baseline assessment for a lifestyle physical activity intervention trial. The ConQuest software was used to assess model fit, item difficulty, item functioning and standard error of measurement. For all scales, the partial credit model fit the data. Item content of one scale did not adequately cover all respondents. Response options of each scale were not targeting respondents appropriately, and standard error of measurement varied across the total score continuum of each scale. These findings indicate that each scale's effectiveness at detecting differences among individuals may be limited unless changes in scale content and response format are made. PMID:16849389

  20. Active Transport and Diffusion Barriers Restrict Joubert Syndrome-Associated ARL13B/ARL-13 to an Inv-like Ciliary Membrane Subdomain

    PubMed Central

    Cevik, Sebiha; Clarke, Lara; van Reeuwijk, Jeroen; Hori, Yuji; Horn, Nicola; Hetterschijt, Lisette; Wdowicz, Anita; Mullins, Andrea; Kida, Katarzyna; Kaplan, Oktay I.; van Beersum, Sylvia E. C.; Man Wu, Ka; Letteboer, Stef J. F.; Mans, Dorus A.; Katada, Toshiaki; Kontani, Kenji; Ueffing, Marius; Roepman, Ronald; Kremer, Hannie; Blacque, Oliver E.

    2013-01-01

    Cilia are microtubule-based cell appendages, serving motility, chemo-/mechano-/photo- sensation, and developmental signaling functions. Cilia are comprised of distinct structural and functional subregions including the basal body, transition zone (TZ) and inversin (Inv) compartments, and defects in this organelle are associated with an expanding spectrum of inherited disorders including Bardet-Biedl syndrome (BBS), Meckel-Gruber Syndrome (MKS), Joubert Syndrome (JS) and Nephronophthisis (NPHP). Despite major advances in understanding ciliary trafficking pathways such as intraflagellar transport (IFT), how proteins are transported to subciliary membranes remains poorly understood. Using Caenorhabditis elegans and mammalian cells, we investigated the transport mechanisms underlying compartmentalization of JS-associated ARL13B/ARL-13, which we previously found is restricted at proximal ciliary membranes. We now show evolutionary conservation of ARL13B/ARL-13 localisation to an Inv-like subciliary membrane compartment, excluding the TZ, in many C. elegans ciliated neurons and in a subset of mammalian ciliary subtypes. Compartmentalisation of C. elegans ARL-13 requires a C-terminal RVVP motif and membrane anchoring to prevent distal cilium and nuclear targeting, respectively. Quantitative imaging in more than 20 mutants revealed differential contributions for IFT and ciliopathy modules in defining the ARL-13 compartment; IFT-A/B, IFT-dynein and BBS genes prevent ARL-13 accumulation at periciliary membranes, whereas MKS/NPHP modules additionally inhibit ARL-13 association with TZ membranes. Furthermore, in vivo FRAP analyses revealed distinct roles for IFT and MKS/NPHP genes in regulating a TZ barrier to ARL-13 diffusion, and intraciliary ARL-13 diffusion. Finally, C. elegans ARL-13 undergoes IFT-like motility and quantitative protein complex analysis of human ARL13B identified functional associations with IFT-B complexes, mapped to IFT46 and IFT74 interactions. Together

  1. Reliability and construct validity of the Participation in Life Activities Scale for children and adolescents with asthma: an instrument evaluation study

    PubMed Central

    Kintner, Eileen K; Sikorskii, Alla

    2008-01-01

    Background The purpose of this study was to evaluate the reliability and construct validity of the Participation in Life Activities Scale, an instrument designed to measure older school-age child and early adolescent level of involvement in chosen pursuits. Methods A cross-sectional design was used. The convenience sample consisted of 313 school-age children and early adolescents with asthma, ages 9–15 years. The self-report summative scale of interest is a 3-indicator survey. Higher scores are reflective of higher levels of participation. Internal consistency reliability and construct validity for the entire sample and sub groups of the sample were evaluated. Results The instrument was deemed sound for the entire sample as well as sub groups based on sex, race, age, socioeconomic status, and severity of illness. Cronbach's alpha coefficient for internal consistency reliability for the entire sample was .74. Exploratory factor analysis indicated a single component solution (loadings .79–.85) accounting for 66% of the explained variance. Construct validity was established by testing the posed relationship between participation in life activities scores and severity of illness. Confirmatory factor analysis revealed a good fit between the data and specified model, χ2(10, n = 302) = 8.074, p = .62. Conclusion This instrument could be used (a) in clinical settings to diagnose restricted participation in desired activities, guide decision-making about treatment plans to increase participation, and motivate behavioral change in the management of asthma; and (b) in research settings to explore factors influencing and consequences of restricted and unrestricted participation, and as an outcome measure to evaluate the effectiveness of programs designed to foster child and early adolescent management of asthma. PMID:18533017

  2. Identification of active denitrifiers in full-scale nutrient removal wastewater treatment systems.

    PubMed

    McIlroy, Simon Jon; Starnawska, Anna; Starnawski, Piotr; Saunders, Aaron Marc; Nierychlo, Marta; Nielsen, Per Halkjaer; Nielsen, Jeppe Lund

    2016-01-01

    Denitrification is essential to the removal of nitrogen from wastewater during treatment, yet an understanding of the diversity of the active denitrifying bacteria responsible in full-scale wastewater treatment plants (WWTPs) is lacking. In this study, stable-isotope probing (SIP) was applied in combination with microautoradiography (MAR)-fluorescence in situ hybridization (FISH) to identify previously unrecognized active denitrifying phylotypes in a full-scale WWTP with biological N and P removal. Acknowledging that different denitrifiers will have specific carbon source preferences, a fully (13)C-labelled complex substrate was used for SIP incubations, under nitrite-reducing conditions, in order to maximize the capture of the potentially metabolically diverse denitrifiers likely present. Members of the Rhodoferax, Dechloromonas, Sulfuritalea, Haliangium and Thermomonas were represented in the 16S rRNA gene clone libraries from DNA enriched in (13)C, with FISH probes optimized here for their in situ characterization. FISH and MAR confirmed that they were all active denitrifiers in the community. The combined approach of SIP and MAR-FISH represents an excellent approach for identifying and characterizing an un-described diversity of active denitrifiers in full-scale systems. PMID:25181571

  3. Active mechanics in living oocytes reveal molecular-scale force kinetics

    NASA Astrophysics Data System (ADS)

    Ahmed, Wylie; Fodor, Etienne; Almonacid, Maria; Bussonnier, Matthias; Verlhac, Marie-Helene; Gov, Nir; Visco, Paolo; van Wijland, Frederic; Betz, Timo

    Unlike traditional materials, living cells actively generate forces at the molecular scale that change their structure and mechanical properties. This nonequilibrium activity is essential for cellular function, and drives processes such as cell division. Single molecule studies have uncovered the detailed force kinetics of isolated motor proteins in-vitro, however their behavior in-vivo has been elusive due to the complex environment inside the cell. Here, we quantify active forces and intracellular mechanics in living oocytes using in-vivo optical trapping and laser interferometry of endogenous vesicles. We integrate an experimental and theoretical framework to connect mesoscopic measurements of nonequilibrium properties to the underlying molecular- scale force kinetics. Our results show that force generation by myosin-V drives the cytoplasmic-skeleton out-of-equilibrium (at frequencies below 300 Hz) and actively softens the environment. In vivo myosin-V activity generates a force of F ~ 0 . 4 pN, with a power-stroke of length Δx ~ 20 nm and duration τ ~ 300 μs, that drives vesicle motion at vv ~ 320 nm/s. This framework is widely applicable to characterize living cells and other soft active materials.

  4. Large-Scale Coronal Heating from "Cool" Activity in the Solar Magnetic Network

    NASA Technical Reports Server (NTRS)

    Falconer, D. A.; Moore, R. L.; Porter, J. G.; Hathaway, D. H.

    1999-01-01

    In Fe XII images from SOHO/EIT, the quiet solar corona shows structure on scales ranging from sub-supergranular (i.e., bright points and coronal network) to multi-supergranular (large-scale corona). In Falconer et al 1998 (Ap.J., 501, 386) we suppressed the large-scale background and found that the network-scale features are predominantly rooted in the magnetic network lanes at the boundaries of the supergranules. Taken together, the coronal network emission and bright point emission are only about 5% of the entire quiet solar coronal Fe XII emission. Here we investigate the relationship between the large-scale corona and the network as seen in three different EIT filters (He II, Fe IX-X, and Fe XII). Using the median-brightness contour, we divide the large-scale Fe XII corona into dim and bright halves, and find that the bright-half/dim half brightness ratio is about 1.5. We also find that the bright half relative to the dim half has 10 times greater total bright point Fe XII emission, 3 times greater Fe XII network emission, 2 times greater Fe IX-X network emission, 1.3 times greater He II network emission, and has 1.5 times more magnetic flux. Also, the cooler network (He II) radiates an order of magnitude more energy than the hotter coronal network (Fe IX-X, and Fe XII). From these results we infer that: 1) The heating of the network and the heating of the large-scale corona each increase roughly linearly with the underlying magnetic flux. 2) The production of network coronal bright points and heating of the coronal network each increase nonlinearly with the magnetic flux. 3) The heating of the large-scale corona is driven by widespread cooler network activity rather than by the exceptional network activity that produces the network coronal bright points and the coronal network. 4) The large-scale corona is heated by a nonthermal process since the driver of its heating is cooler than it is. This work was funded by the Solar Physics Branch of NASA's office of

  5. Seasonal prediction of lightning activity in North Western Venezuela: Large-scale versus local drivers

    NASA Astrophysics Data System (ADS)

    Muñoz, Á. G.; Díaz-Lobatón, J.; Chourio, X.; Stock, M. J.

    2016-05-01

    The Lake Maracaibo Basin in North Western Venezuela has the highest annual lightning rate of any place in the world (~ 200 fl km- 2 yr- 1), whose electrical discharges occasionally impact human and animal lives (e.g., cattle) and frequently affect economic activities like oil and natural gas exploitation. Lightning activity is so common in this region that it has a proper name: Catatumbo Lightning (plural). Although short-term lightning forecasts are now common in different parts of the world, to the best of the authors' knowledge, seasonal prediction of lightning activity is still non-existent. This research discusses the relative role of both large-scale and local climate drivers as modulators of lightning activity in the region, and presents a formal predictability study at seasonal scale. Analysis of the Catatumbo Lightning Regional Mode, defined in terms of the second Empirical Orthogonal Function of monthly Lightning Imaging Sensor (LIS-TRMM) and Optical Transient Detector (OTD) satellite data for North Western South America, permits the identification of potential predictors at seasonal scale via a Canonical Correlation Analysis. Lightning activity in North Western Venezuela responds to well defined sea-surface temperature patterns (e.g., El Niño-Southern Oscillation, Atlantic Meridional Mode) and changes in the low-level meridional wind field that are associated with the Inter-Tropical Convergence Zone migrations, the Caribbean Low Level Jet and tropical cyclone activity, but it is also linked to local drivers like convection triggered by the topographic configuration and the effect of the Maracaibo Basin Nocturnal Low Level Jet. The analysis indicates that at seasonal scale the relative contribution of the large-scale drivers is more important than the local (basin-wide) ones, due to the synoptic control imposed by the former. Furthermore, meridional CAPE transport at 925 mb is identified as the best potential predictor for lightning activity in the Lake

  6. Restriction/modification polypeptides, polynucleotides, and methods

    SciTech Connect

    Westpheling, Janet; Chung, DaeHwan; Huddleston, Jennifer; Farkas, Joel A

    2015-02-24

    The present invention relates to the discovery of a novel restriction/modification system in Caldicellulosiruptor bescii. The discovered restriction enzyme is a HaeIII-like restriction enzyme that possesses a thermophilic activity profile. The restriction/modification system also includes a methyltransferase, M.CbeI, that methylates at least one cytosine residue in the CbeI recognition sequence to m.sup.4C. Thus, the invention provides, in various aspects, isolated CbeI or M.CbeI polypeptides, or biologically active fragments thereof; isolated polynucleotides that encode the CbeI or M.CbeI polypeptides or biologically active fragments thereof, including expression vectors that include such polynucleotide sequences; methods of digesting DNA using a CbeI polypeptide; methods of treating a DNA molecule using a M.CbeI polypeptide; and methods of transforming a Caldicellulosiruptor cell.

  7. Activation of Nonclassical CD1d-Restricted NK T Cells Induces Airway Hyperreactivity in β2-Microglobulin-Deficient Mice1

    PubMed Central

    Meyer, Everett H.; Pichavant, Muriel; Akbari, Omid; Yasumi, Takahiro; Savage, Paul B.; DeKruyff, Rosemarie H.; Umetsu, Dale T.

    2016-01-01

    Allergic asthma is characterized by Th2-driven eosinophilic airway inflammation and by a central feature called airway hyperreactivity (AHR), development of which requires the presence of classical type I invariant NK T (iNKT) cells. Allergen-induced AHR, however, develops in β2-microglobulin (β2m)−/− mice, which lack classical iNKT cells, suggesting that in some situations iNKT cells may be dispensable for the development of AHR. In contrast, our studies now suggest that a CD1d-restricted, NK1.1+ noninvariant TCR NKT cell population is present in β2m−/− mice and is responsible for the development of AHR but not for Th2 responses. Furthermore, treatment of β2m−/− mice with anti-CD1d mAb or anti-NK1.1 mAb unexpectedly abolished allergen-induced AHR. The CD1-restricted NKT cells in these mice, which failed to respond to α-galactosylceramide and which therefore were not classical type I iNKT cells, appear to represent an NKT cell subset restricted by a β2m-independent form of CD1d. These results indicate that, although classical type I iNKT cells are normally required for the development of AHR, under different circumstances other NKT cell subsets, including nonclassical NKT cells, may substitute for classical iNKT cells and induce AHR. PMID:18802058

  8. Active open boundary forcing using dual relaxation time-scales in downscaled ocean models

    NASA Astrophysics Data System (ADS)

    Herzfeld, M.; Gillibrand, P. A.

    2015-05-01

    Regional models actively forced with data from larger scale models at their open boundaries often contain motion at different time-scales (e.g. tidal and low frequency). These motions are not always individually well specified in the forcing data, and one may require a more active boundary forcing while the other exert less influence on the model interior. If a single relaxation time-scale is used to relax toward these data in the boundary equation, then this may be difficult. The method of fractional steps is used to introduce dual relaxation time-scales in an open boundary local flux adjustment scheme. This allows tidal and low frequency oscillations to be relaxed independently, resulting in a better overall solution than if a single relaxation parameter is optimized for tidal (short relaxation) or low frequency (long relaxation) boundary forcing. The dual method is compared to the single relaxation method for an idealized test case where a tidal signal is superimposed on a steady state low frequency solution, and a real application where the low frequency boundary forcing component is derived from a global circulation model for a region extending over the whole Great Barrier Reef, and a tidal signal subsequently superimposed.

  9. Continuous clarification and thickening of activated sludge by electrolytic bubbles under control of scale deposition.

    PubMed

    Cho, Kang Woo; Chung, Chong Min; Kim, Yun Jung; Chung, Tai Hak

    2010-05-01

    Electroflotation (EF) was investigated as a final clarification of an activated sludge process, to intensify its novel clarification and thickening efficiency. During operation of a biological reactor combined with an EF clarifier, deterioration of clarification efficiency was observed. Scale deposition on electrodes caused a coarse electrode surface, significantly increasing the size of the electrolytic bubbles. The average bubble size was initially 34 microm and increased to 80 microm after bulk cell electrolysis for 150 h. X-ray diffractometry and scanning electron microscopy further characterized the scale deposition as a cluster of calcite (CaCO(3)) and brucite (Mg(OH)(2)). Switching the polarity of electrical current clearly alleviated the increase of bubble size, when applied before scale growth. Under the control of scale deposition, excellent clarification was observed, with the effluent turbidity consistently lower than 2 NTU. An efficient thickening, with the concentration of return activated sludge higher than 15 g L(-1), was additional advantage of the EF clarifier. PMID:20071165

  10. Spontaneous Neuronal Activity in Developing Neocortical Networks: From Single Cells to Large-Scale Interactions

    PubMed Central

    Luhmann, Heiko J.; Sinning, Anne; Yang, Jenq-Wei; Reyes-Puerta, Vicente; Stüttgen, Maik C.; Kirischuk, Sergei; Kilb, Werner

    2016-01-01

    Neuronal activity has been shown to be essential for the proper formation of neuronal circuits, affecting developmental processes like neurogenesis, migration, programmed cell death, cellular differentiation, formation of local and long-range axonal connections, synaptic plasticity or myelination. Accordingly, neocortical areas reveal distinct spontaneous and sensory-driven neuronal activity patterns already at early phases of development. At embryonic stages, when immature neurons start to develop voltage-dependent channels, spontaneous activity is highly synchronized within small neuronal networks and governed by electrical synaptic transmission. Subsequently, spontaneous activity patterns become more complex, involve larger networks and propagate over several neocortical areas. The developmental shift from local to large-scale network activity is accompanied by a gradual shift from electrical to chemical synaptic transmission with an initial excitatory action of chloride-gated channels activated by GABA, glycine and taurine. Transient neuronal populations in the subplate (SP) support temporary circuits that play an important role in tuning early neocortical activity and the formation of mature neuronal networks. Thus, early spontaneous activity patterns control the formation of developing networks in sensory cortices, and disturbances of these activity patterns may lead to long-lasting neuronal deficits. PMID:27252626

  11. Spontaneous Neuronal Activity in Developing Neocortical Networks: From Single Cells to Large-Scale Interactions.

    PubMed

    Luhmann, Heiko J; Sinning, Anne; Yang, Jenq-Wei; Reyes-Puerta, Vicente; Stüttgen, Maik C; Kirischuk, Sergei; Kilb, Werner

    2016-01-01

    Neuronal activity has been shown to be essential for the proper formation of neuronal circuits, affecting developmental processes like neurogenesis, migration, programmed cell death, cellular differentiation, formation of local and long-range axonal connections, synaptic plasticity or myelination. Accordingly, neocortical areas reveal distinct spontaneous and sensory-driven neuronal activity patterns already at early phases of development. At embryonic stages, when immature neurons start to develop voltage-dependent channels, spontaneous activity is highly synchronized within small neuronal networks and governed by electrical synaptic transmission. Subsequently, spontaneous activity patterns become more complex, involve larger networks and propagate over several neocortical areas. The developmental shift from local to large-scale network activity is accompanied by a gradual shift from electrical to chemical synaptic transmission with an initial excitatory action of chloride-gated channels activated by GABA, glycine and taurine. Transient neuronal populations in the subplate (SP) support temporary circuits that play an important role in tuning early neocortical activity and the formation of mature neuronal networks. Thus, early spontaneous activity patterns control the formation of developing networks in sensory cortices, and disturbances of these activity patterns may lead to long-lasting neuronal deficits. PMID:27252626

  12. Evidence of parsec-scale jets in low-luminosity active galactic nuclei

    SciTech Connect

    Mezcua, M.; Prieto, M. A.

    2014-05-20

    The nuclear radio emission of low-luminosity active galactic nuclei (LLAGNs) is often associated with unresolved cores. In this paper we show that most LLAGNs present extended jet radio emission when observed with sufficient angular resolution and sensitivity. They are thus able to power, at least, parsec-scale radio jets. To increase the detection rate of jets in LLAGNs, we analyze subarcsecond resolution data of three low-ionization nuclear emission regions. This yields the detection of extended jet-like radio structures in NGC 1097 and NGC 2911 and the first resolved parsec-scale jet of NGC 4594 (Sombrero). The three sources belong to a sample of nearby LLAGNs for which high-spatial-resolution spectral energy distribution of their core emission is available. This allows us to study their accretion rate and jet power (Q {sub jet}) without drawing on (most) of the ad hoc assumptions usually considered in large statistical surveys. We find that those LLAGNs with large-scale radio jets (>100 pc) have Q {sub jet} > 10{sup 42} erg s{sup –1}, while the lowest Q {sub jet} correspond to those LLAGNs with parsec-scale (≤100 pc) jets. The Q {sub jet} is at least as large as the radiated bolometric luminosity for all LLAGN, in agreement with previous statistical studies. Our detection of parsec-scale jets in individual objects further shows that the kinematic jet contribution is equally important in large- or parsec-scale objects. We also find that the Eddington-scaled accretion rate is still highly sub-Eddingtonian (<10{sup –4}) when adding the Q {sub jet} to the total emitted luminosity (radiated plus kinetic). This indicates that LLAGNs are not only inefficient radiators but that they also accrete inefficiently or are very efficient advectors.

  13. Evidence of Parsec-scale Jets in Low-luminosity Active Galactic Nuclei

    NASA Astrophysics Data System (ADS)

    Mezcua, M.; Prieto, M. A.

    2014-05-01

    The nuclear radio emission of low-luminosity active galactic nuclei (LLAGNs) is often associated with unresolved cores. In this paper we show that most LLAGNs present extended jet radio emission when observed with sufficient angular resolution and sensitivity. They are thus able to power, at least, parsec-scale radio jets. To increase the detection rate of jets in LLAGNs, we analyze subarcsecond resolution data of three low-ionization nuclear emission regions. This yields the detection of extended jet-like radio structures in NGC 1097 and NGC 2911 and the first resolved parsec-scale jet of NGC 4594 (Sombrero). The three sources belong to a sample of nearby LLAGNs for which high-spatial-resolution spectral energy distribution of their core emission is available. This allows us to study their accretion rate and jet power (Q jet) without drawing on (most) of the ad hoc assumptions usually considered in large statistical surveys. We find that those LLAGNs with large-scale radio jets (>100 pc) have Q jet > 1042 erg s-1, while the lowest Q jet correspond to those LLAGNs with parsec-scale (<=100 pc) jets. The Q jet is at least as large as the radiated bolometric luminosity for all LLAGN, in agreement with previous statistical studies. Our detection of parsec-scale jets in individual objects further shows that the kinematic jet contribution is equally important in large- or parsec-scale objects. We also find that the Eddington-scaled accretion rate is still highly sub-Eddingtonian (<10-4) when adding the Q jet to the total emitted luminosity (radiated plus kinetic). This indicates that LLAGNs are not only inefficient radiators but that they also accrete inefficiently or are very efficient advectors.

  14. Summary Report on FY12 Small-Scale Test Activities High Temperature Electrolysis Program

    SciTech Connect

    James O'Brien

    2012-09-01

    This report provides a description of the apparatus and the single cell testing results performed at Idaho National Laboratory during January–August 2012. It is an addendum to the Small-Scale Test Report issued in January 2012. The primary program objectives during this time period were associated with design, assembly, and operation of two large experiments: a pressurized test, and a 4 kW test. Consequently, the activities described in this report represent a much smaller effort.

  15. Millisecond time scale atmospheric light pulses associated with solar and magnetospheric activity.

    NASA Technical Reports Server (NTRS)

    Ogelman, H.

    1973-01-01

    By using a wide-angle photomultiplier system a class of millisecond time scale diffuse atmospheric light emission of terrestrial origin has been discovered. These fast atmospheric pulsation events also show damped oscillations around 10-kHz frequency, which distinguishes them from ordinary lightning-type events. Evidence is presented for the enhancement in the rate of these events induced by solar flare activity.

  16. Temporal Taylor's scaling of facial electromyography and electrodermal activity in the course of emotional stimulation

    NASA Astrophysics Data System (ADS)

    Chołoniewski, Jan; Chmiel, Anna; Sienkiewicz, Julian; Hołyst, Janusz A.; Küster, Dennis; Kappas, Arvid

    2016-09-01

    High frequency psychophysiological data create a challenge for quantitative modeling based on Big Data tools since they reflect the complexity of processes taking place in human body and its responses to external events. Here we present studies of fluctuations in facial electromyography (fEMG) and electrodermal activity (EDA) massive time series and changes of such signals in the course of emotional stimulation. Zygomaticus major (ZYG, "smiling" muscle) activity, corrugator supercilii (COR, "frowning"bmuscle) activity, and phasic skin conductance (PHSC, sweating) levels of 65 participants were recorded during experiments that involved exposure to emotional stimuli (i.e., IAPS images, reading and writing messages on an artificial online discussion board). Temporal Taylor's fluctuations scaling were found when signals for various participants and during various types of emotional events were compared. Values of scaling exponents were close to 1, suggesting an external origin of system dynamics and/or strong interactions between system's basic elements (e.g., muscle fibres). Our statistical analysis shows that the scaling exponents enable identification of high valence and arousal levels in ZYG and COR signals.

  17. The Possibilities for Activity Scale (PActS): Development, validity, and reliability

    PubMed Central

    Pergolotti, Mackenzi; Cutchin, Malcolm P.

    2016-01-01

    Background Laliberte-Rudman (2005) proposed the concept of occupational possibilities to represent what older adults feel they “should be” and “could be” doing. Purpose This study aimed to develop and validate a measure of perceived occupational possibilities: the Possibilities for Activity Scale (PActS). Method Two factors of the PActS, activity expectations and activity self-efficacy, were operationalized in a 14-item instrument. The instrument was then evaluated with a sample of older adults diagnosed with cancer (n = 179). Findings The PActS demonstrated promising internal consistency reliability (stratified coefficient α =.77) and construct-related (r =. 58; p < .0001), structural (Chi-square, 61.57; CFI, .97; RMSEA, 0.05; TLI, .96; NFI, .91) and known-groups validity. Implications The PActS appears to be a useful measure of internalized occupational possibilities for participation in activity for older adults with cancer. This scale can enhance the measurement of participation in activity by evaluating the perceptions of occupational possibilities. PMID:26281432

  18. Imaging large-scale cellular activity in spinal cord of freely behaving mice.

    PubMed

    Sekiguchi, Kohei J; Shekhtmeyster, Pavel; Merten, Katharina; Arena, Alexander; Cook, Daniela; Hoffman, Elizabeth; Ngo, Alexander; Nimmerjahn, Axel

    2016-01-01

    Sensory information from mechanoreceptors and nociceptors in the skin plays key roles in adaptive and protective motor behaviours. To date, very little is known about how this information is encoded by spinal cord cell types and their activity patterns, particularly under freely behaving conditions. To enable stable measurement of neuronal and glial cell activity in behaving mice, we have developed fluorescence imaging approaches based on two- and miniaturized one-photon microscopy. We show that distinct cutaneous stimuli activate overlapping ensembles of dorsal horn neurons, and that stimulus type and intensity is encoded at the single-cell level. In contrast, astrocytes show large-scale coordinated calcium responses to intense but not weak sensory inputs. Sensory-evoked activity is potently suppressed by anaesthesia. By revealing the cellular and computational logic of spinal cord networks under behaving conditions, our approach holds promise for better understanding of healthy and aberrant spinal cord processes. PMID:27121084

  19. Imaging large-scale cellular activity in spinal cord of freely behaving mice

    PubMed Central

    Sekiguchi, Kohei J.; Shekhtmeyster, Pavel; Merten, Katharina; Arena, Alexander; Cook, Daniela; Hoffman, Elizabeth; Ngo, Alexander; Nimmerjahn, Axel

    2016-01-01

    Sensory information from mechanoreceptors and nociceptors in the skin plays key roles in adaptive and protective motor behaviours. To date, very little is known about how this information is encoded by spinal cord cell types and their activity patterns, particularly under freely behaving conditions. To enable stable measurement of neuronal and glial cell activity in behaving mice, we have developed fluorescence imaging approaches based on two- and miniaturized one-photon microscopy. We show that distinct cutaneous stimuli activate overlapping ensembles of dorsal horn neurons, and that stimulus type and intensity is encoded at the single-cell level. In contrast, astrocytes show large-scale coordinated calcium responses to intense but not weak sensory inputs. Sensory-evoked activity is potently suppressed by anaesthesia. By revealing the cellular and computational logic of spinal cord networks under behaving conditions, our approach holds promise for better understanding of healthy and aberrant spinal cord processes. PMID:27121084

  20. Restricting mutualistic partners to enforce trade reliance.

    PubMed

    Wyatt, Gregory A K; Kiers, E Toby; Gardner, Andy; West, Stuart A

    2016-01-01

    Mutualisms are cooperative interactions between members of different species, often involving the trade of resources. Here, we suggest that otherwise-cooperative mutualists might be able to gain a benefit from actively restricting their partners' ability to obtain resources directly, hampering the ability of the restricted partner to survive and/or reproduce without the help of the restricting mutualist. We show that (i) restriction can be favoured when it makes the resources of the restricting individual more valuable to their partner, and thus allows them to receive more favourable terms of trade; (ii) restriction maintains cooperation in conditions where cooperative behaviour would otherwise collapse; and (iii) restriction can lead to either an increase or decrease in a restricted individual's fitness. We discuss the applicability of this scenario to mutualisms such as those between plants and mycorrhizal fungi. These results identify a novel conflict in mutualisms as well as several public goods dilemmas, but also demonstrate how conflict can help maintain cooperation. PMID:26813888

  1. Restricting mutualistic partners to enforce trade reliance

    PubMed Central

    Wyatt, Gregory A. K.; Kiers, E. Toby; Gardner, Andy; West, Stuart A.

    2016-01-01

    Mutualisms are cooperative interactions between members of different species, often involving the trade of resources. Here, we suggest that otherwise-cooperative mutualists might be able to gain a benefit from actively restricting their partners' ability to obtain resources directly, hampering the ability of the restricted partner to survive and/or reproduce without the help of the restricting mutualist. We show that (i) restriction can be favoured when it makes the resources of the restricting individual more valuable to their partner, and thus allows them to receive more favourable terms of trade; (ii) restriction maintains cooperation in conditions where cooperative behaviour would otherwise collapse; and (iii) restriction can lead to either an increase or decrease in a restricted individual's fitness. We discuss the applicability of this scenario to mutualisms such as those between plants and mycorrhizal fungi. These results identify a novel conflict in mutualisms as well as several public goods dilemmas, but also demonstrate how conflict can help maintain cooperation. PMID:26813888

  2. RESPONSIVENESS OF THE ACTIVITIES OF DAILY LIVING SCALE OF THE KNEE OUTCOME SURVEY AND NUMERIC PAIN RATING SCALE IN PATIENTS WITH PATELLOFEMORAL PAIN

    PubMed Central

    Piva, Sara R.; Gil, Alexandra B.; Moore, Charity G.; Fitzgerald, G. Kelley

    2016-01-01

    Objective To assess internal and external responsiveness of the Activity of Daily Living Scale of the Knee Outcome Survey and Numeric Pain Rating Scale on patients with patellofemoral pain. Design One group pre-post design. Subjects A total of 60 individuals with patellofemoral pain (33 women; mean age 29.9 (standard deviation 9.6) years). Methods The Activity of Daily Living Scale and the Numeric Pain Rating Scale were assessed before and after 8 weeks of physical therapy program. Patients completed a global rating of change scale at the end of therapy. The standardized effect size, Guyatt responsiveness index, and the minimum clinical important difference were calculated. Results Standardized effect size of the Activity of Daily Living Scale was 0.63, Guyatt responsiveness index was 1.4, area under the curve was 0.83 (95% confidence interval: 0.72, 0.94), and the minimum clinical important difference corresponded to an increase of 7.1 percentile points. Standardized effect size of the Numeric Pain Rating Scale was 0.72, Guyatt responsiveness index was 2.2, area under the curve was 0.80 (95% confidence interval: 0.70, 0.92), and the minimum clinical important difference corresponded to a decrease of 1.16 points. Conclusion Information from this study may be helpful to therapists when evaluating the effectiveness of rehabilitation intervention on physical function and pain, and to power future clinical trials on patients with patellofemoral pain. PMID:19229444

  3. Tracking and visualization of space-time activities for a micro-scale flu transmission study

    PubMed Central

    2013-01-01

    Background Infectious diseases pose increasing threats to public health with increasing population density and more and more sophisticated social networks. While efforts continue in studying the large scale dissemination of contagious diseases, individual-based activity and behaviour study benefits not only disease transmission modelling but also the control, containment, and prevention decision making at the local scale. The potential for using tracking technologies to capture detailed space-time trajectories and model individual behaviour is increasing rapidly, as technological advances enable the manufacture of small, lightweight, highly sensitive, and affordable receivers and the routine use of location-aware devices has become widespread (e.g., smart cellular phones). The use of low-cost tracking devices in medical research has also been proved effective by more and more studies. This study describes the use of tracking devices to collect data of space-time trajectories and the spatiotemporal processing of such data to facilitate micro-scale flu transmission study. We also reports preliminary findings on activity patterns related to chances of influenza infection in a pilot study. Methods Specifically, this study employed A-GPS tracking devices to collect data on a university campus. Spatiotemporal processing was conducted for data cleaning and segmentation. Processed data was validated with traditional activity diaries. The A-GPS data set was then used for visual explorations including density surface visualization and connection analysis to examine space-time activity patterns in relation to chances of influenza infection. Results When compared to diary data, the segmented tracking data demonstrated to be an effective alternative and showed greater accuracies in time as well as the details of routes taken by participants. A comparison of space-time activity patterns between participants who caught seasonal influenza and those who did not revealed interesting

  4. Scaling up of HIV-TB collaborative activities: Achievements and challenges in India.

    PubMed

    Deshmukh, Rajesh; Shah, Amar; Sachdeva, K S; Sreenivas, A N; Gupta, R S; Khaparde, S D

    2016-01-01

    India has been implementing HIV/TB collaborative activities since 2001 with rapid scale-up of infrastructure across the country during past decade in National AIDS Control Programme and Revised National TB Control Programme. India has shown over 50% reduction in new infections and around 35% reduction in AIDS-related deaths, thereby being one of the success stories globally. Substantial progress in the implementation of collaborative TB/HIV activities has occurred in India and it is marching towards target set out in the Global Plan to Stop TB and endorsed by the UN General Assembly to halve HIV associated TB deaths by 2015. While the successful approaches have led to impressive gains in HIV/TB control in India, there are emerging challenges including newer pockets with rising HIV trends in North India, increasing drug resistance, high mortality among co-infected patients, low HIV testing rates among TB patients in northern and eastern states in India, treatment delays and drop-outs, stigma and discrimination, etc. In spite of these difficulties, established HIV/TB coordination mechanisms at different levels, rapid scale-up of facilities with decentralisation of treatment services, regular joint supervision and monitoring, newer initiatives like use of rapid diagnostics for early diagnosis of TB among people living with HIV, TB notification, etc. have led to success in combating the threat of HIV/TB in India. This article highlights the steps taken by India, one of the largest HIV/TB programmes in world, in scaling up of the joint HIV-TB collaborative activities, the achievements so far and discusses the emerging challenges which could provide important lessons for other countries in scaling up their programmes. PMID:27235937

  5. 7 CFR 1710.125 - Restrictions on lobbying.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... and Basic Policies § 1710.125 Restrictions on lobbying. Borrowers are required to comply with certain requirements with respect to restrictions on lobbying activities. See 7 CFR part 3018. ... 7 Agriculture 11 2010-01-01 2010-01-01 false Restrictions on lobbying. 1710.125 Section...

  6. 33 CFR 141.15 - Restrictions on employment.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 33 Navigation and Navigable Waters 2 2010-07-01 2010-07-01 false Restrictions on employment. 141.15 Section 141.15 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES PERSONNEL Restrictions on Employment § 141.15 Restrictions...

  7. 33 CFR 141.15 - Restrictions on employment.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 33 Navigation and Navigable Waters 2 2011-07-01 2011-07-01 false Restrictions on employment. 141.15 Section 141.15 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES PERSONNEL Restrictions on Employment § 141.15 Restrictions...

  8. 33 CFR 141.15 - Restrictions on employment.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 2 2014-07-01 2014-07-01 false Restrictions on employment. 141.15 Section 141.15 Navigation and Navigable Waters COAST GUARD, DEPARTMENT OF HOMELAND SECURITY (CONTINUED) OUTER CONTINENTAL SHELF ACTIVITIES PERSONNEL Restrictions on Employment § 141.15 Restrictions on employment. (a) Each employer of personnel...

  9. Activity-dependent scaling of GABAergic synapse strength is regulated by brain-derived neurotrophic factor

    PubMed Central

    Swanwick, Catherine Croft; Murthy, Namita R.; Kapur, Jaideep

    2010-01-01

    The homeostatic plasticity hypothesis suggests that neuronal activity scales synaptic strength. This study analyzed effects of activity deprivation on GABAergic synapses in cultured hippocampal neurons using patch clamp electrophysiology to record mIPSCs and immunocytochemistry to visualize presynaptic GAD-65 and the γ2 subunit of the GABAA receptor. When neural activity was blocked for 48 h with tetrodotoxin (TTX, 1 μM), the amplitude of mIPSCs was reduced, corresponding with diminished sizes of GAD-65 puncta and γ2 clusters. Treatment with the NMDA receptor antagonist APV (50 μM) or the AMPA receptor antagonist DNQX (20 μM) mimicked these effects, and co-application of brain-derived neurotrophic factor (BDNF, 100 ng/mL) overcame them. Moreover, when neurons were treated with BDNF alone for 48 h, these effects were reversed via the TrkB receptor. Overall, these results suggest that activity-dependent scaling of inhibitory synaptic strength can be modulated by BDNF/TrkB-mediated signaling. PMID:16330218

  10. Reconstruction of the solar coronal magnetic field, from active region to large scale

    NASA Astrophysics Data System (ADS)

    Amari, T.; Canou, A.; Delyon, F.; Aly, J. J.; Frey, P.; Alauzet, F.

    2011-12-01

    The low solar corona is dominated by the magnetic field which is created inside the sun by a dynamo process and then emerges into the atmosphere. This magnetic field plays an important role in most structures and phenomena observed at various wavelengths such as prominences, small and large scale eruptive events, and continuous heating of the plasma, and therefore it is important to understand its three-dimensional properties in order to elaborate efficient theoretical models. Unfortunately, the magnetic field is difficult to measure locally in the hot and tenuous corona. But this can be done at the level of the cooler and denser photosphere, and several instruments with high resolution vector magnetographs are currently available (THEMIS, Imaging Vector Magnetograph (IVM), the Advanced Stokes Polarimeter (ASP), SOLIS, HINODE, Solar Dynamics Observatory (SDO), or will be shortly available by future telescopes such as EST and solar missions as SOLAR-ORBITER. This has lead solar physicists to develop an approach which consists in " reconstructing" the coronal magnetic field from boundary data given on the photosphere. We will discuss some of the issues encountered in solving this problem as well our recent progress and results at the scale of active region scales or the larger one such as full sun scale.

  11. Large-scale pattern formation in active particles suspensions: from interacting microtubules to swimming bacteria

    NASA Astrophysics Data System (ADS)

    Aranson, Igor

    2006-03-01

    We consider two biological systems of active particles exhibiting large-scale collective behavior: microtubules interacting with molecular motors and hydrodynamically entrained swimming bacteria. Starting from a generic stochastic microscopic model of inelastically colliding polar rods with an anisotropic interaction kernel, we derive set of equations for the local rods concentration and orientation. Above certain critical density of rods the model exhibits orientational instability and onset of large-scale coherence. For the microtubules and molecular motors system we demonstrate that the orientational instability leads to the formation of vortices and asters seen in recent experiments. Similar approach is applied to colonies of swimming bacteria Bacillus subtilis confined in thin fluid film. The model is formulated in term of two-dimensional equations for local density and orientation of bacteria coupled to the low Reynolds number Navier-Stokes equation for the fluid flow velocity. The collective swimming of bacteria is represented by additional source term in the Navier-Stokes equation. We demonstrate that this system exhibits formation of dynamic large-scale patterns with the typical scale determined by the density of bacteria.

  12. Fishing for Space: Fine-Scale Multi-Sector Maritime Activities Influence Fisher Location Choice

    PubMed Central

    Tidd, Alex N.; Vermard, Youen; Marchal, Paul; Pinnegar, John; Blanchard, Julia L.; Milner-Gulland, E. J.

    2015-01-01

    The European Union and other states are moving towards Ecosystem Based Fisheries Management to balance food production and security with wider ecosystem concerns. Fishing is only one of several sectors operating within the ocean environment, competing for renewable and non-renewable resources that overlap in a limited space. Other sectors include marine mining, energy generation, recreation, transport and conservation. Trade-offs of these competing sectors are already part of the process but attempts to detail how the seas are being utilised have been primarily based on compilations of data on human activity at large spatial scales. Advances including satellite and shipping automatic tracking enable investigation of factors influencing fishers’ choice of fishing grounds at spatial scales relevant to decision-making, including the presence or avoidance of activities by other sectors. We analyse the determinants of English and Welsh scallop-dredging fleet behaviour, including competing sectors, operating in the eastern English Channel. Results indicate aggregate mining activity, maritime traffic, increased fishing costs, and the English inshore 6 and French 12 nautical mile limits negatively impact fishers’ likelihood of fishing in otherwise suitable areas. Past success, net-benefits and fishing within the 12 NM predispose fishers to use areas. Systematic conservation planning has yet to be widely applied in marine systems, and the dynamics of spatial overlap of fishing with other activities have not been studied at scales relevant to fisher decision-making. This study demonstrates fisher decision-making is indeed affected by the real-time presence of other sectors in an area, and therefore trade-offs which need to be accounted for in marine planning. As marine resource extraction demands intensify, governments will need to take a more proactive approach to resolving these trade-offs, and studies such as this will be required as the evidential foundation for

  13. Fishing for space: fine-scale multi-sector maritime activities influence fisher location choice.

    PubMed

    Tidd, Alex N; Vermard, Youen; Marchal, Paul; Pinnegar, John; Blanchard, Julia L; Milner-Gulland, E J

    2015-01-01

    The European Union and other states are moving towards Ecosystem Based Fisheries Management to balance food production and security with wider ecosystem concerns. Fishing is only one of several sectors operating within the ocean environment, competing for renewable and non-renewable resources that overlap in a limited space. Other sectors include marine mining, energy generation, recreation, transport and conservation. Trade-offs of these competing sectors are already part of the process but attempts to detail how the seas are being utilised have been primarily based on compilations of data on human activity at large spatial scales. Advances including satellite and shipping automatic tracking enable investigation of factors influencing fishers' choice of fishing grounds at spatial scales relevant to decision-making, including the presence or avoidance of activities by other sectors. We analyse the determinants of English and Welsh scallop-dredging fleet behaviour, including competing sectors, operating in the eastern English Channel. Results indicate aggregate mining activity, maritime traffic, increased fishing costs, and the English inshore 6 and French 12 nautical mile limits negatively impact fishers' likelihood of fishing in otherwise suitable areas. Past success, net-benefits and fishing within the 12 NM predispose fishers to use areas. Systematic conservation planning has yet to be widely applied in marine systems, and the dynamics of spatial overlap of fishing with other activities have not been studied at scales relevant to fisher decision-making. This study demonstrates fisher decision-making is indeed affected by the real-time presence of other sectors in an area, and therefore trade-offs which need to be accounted for in marine planning. As marine resource extraction demands intensify, governments will need to take a more proactive approach to resolving these trade-offs, and studies such as this will be required as the evidential foundation for future

  14. Neuroaesthetics: range and restrictions.

    PubMed

    Chatterjee, Anjan

    2013-04-01

    Bullot & Reber (B&R) should be commended for highlighting tensions between scientific aesthetics and art history. The question of how each tradition can learn from the other is timely. While I am sympathetic to their views, their diagnosis of the problem appears exaggerated and their solution partial. They underestimate the reach of scientific aesthetics while failing to identify its inherent restrictions. PMID:23507092

  15. Reference Values for the Marx Activity Rating Scale in a Young Athletic Population

    PubMed Central

    Cameron, Kenneth L.; Peck, Karen Y.; Thompson, Brandon S.; Svoboda, Steven J.; Owens, Brett D.; Marshall, Stephen W.

    2015-01-01

    Background: Activity-related patient-reported outcome measures are an important component of assessment after knee ligament injury in young and physically active patients; however, normative data for most activity scales are limited. Objective: To present reference values by sex for the Marx Activity Rating Scale (MARS) within a young and physically active population while accounting for knee ligament injury history and sex. Study Design: Cross-sectional study. Level of Evidence: Level 2. Methods: All incoming freshman entering a US Service Academy in June of 2011 were recruited to participate in this study. MARS was administered to 1169 incoming freshmen (203 women) who consented to participate within the first week of matriculation. All subjects were deemed healthy and medically fit for military service on admission. Subjects also completed a baseline questionnaire that asked for basic demographic information and injury history. We calculated means with standard deviations, medians with interquartile ranges, and percentiles for ordinal and continuous variables, and frequencies and proportions for dichotomous variables. We also compared median scores by sex and history of knee ligament injury using the Kruskal-Wallis test. MARS was the primary outcome of interest. Results: The median MARS score was significantly higher for men when compared with women (χ2 = 13.22, df = 1, P < 0.001) with no prior history of knee ligament injury. In contrast, there was no significant difference in median MARS scores between men and women (χ2 = 0.47, df = 1, P = 0.493) who reported a history of injury. Overall, median MARS scores were significantly higher among those who reported a history of knee ligament injury when compared with those who did not (χ2 = 9.06, df = 1, P = 0.003). Conclusion: Assessing activity as a patient-reported outcome after knee ligament injury is important, and reference values for these instruments need to account for the influence of prior injury and sex

  16. One-hundred-km-scale basins on Enceladus: Evidence for an active ice shell

    NASA Astrophysics Data System (ADS)

    Schenk, Paul M.; McKinnon, William B.

    2009-08-01

    Stereo-derived topographic mapping of ˜50% of Enceladus reveals at least 6 large-scale, ovoid depressions (basins) 90-175 km across and 800-to-1500 m deep and uncorrelated with geologic boundaries. In contrast, the south polar depression is larger and apparently shallower and correlates with active resurfacing. The shape and scale of the basins is inconsistent with impact, geoid surface deflections, or with dynamically supported topography. Isostatic thinning of Enceladus' ice shell associated with upwellings (and tidally-driven ice melting) can plausibly account for these basins. Thinning implies upwarping of the base of the shell of ˜10-20 km beneath the depressions, depending on total shell thickness; loss of near-surface porosity due to enhanced heat flow may also contribute to basin lows. Alternatively, the basins may overly cold, inactive, and hence denser ice, but thermal isostasy alone requires thermal expansion more consistent with clathrate hydrate than water ice.

  17. Multi-scale integration and predictability in resting state brain activity

    PubMed Central

    Kolchinsky, Artemy; van den Heuvel, Martijn P.; Griffa, Alessandra; Hagmann, Patric; Rocha, Luis M.; Sporns, Olaf; Goñi, Joaquín

    2014-01-01

    The human brain displays heterogeneous organization in both structure and function. Here we develop a method to characterize brain regions and networks in terms of information-theoretic measures. We look at how these measures scale when larger spatial regions as well as larger connectome sub-networks are considered. This framework is applied to human brain fMRI recordings of resting-state activity and DSI-inferred structural connectivity. We find that strong functional coupling across large spatial distances distinguishes functional hubs from unimodal low-level areas, and that this long-range functional coupling correlates with structural long-range efficiency on the connectome. We also find a set of connectome regions that are both internally integrated and coupled to the rest of the brain, and which resemble previously reported resting-state networks. Finally, we argue that information-theoretic measures are useful for characterizing the functional organization of the brain at multiple scales. PMID:25104933

  18. Performance Enhancement of a Full-Scale Vertical Tail Model Equipped with Active Flow Control

    NASA Technical Reports Server (NTRS)

    Whalen, Edward A.; Lacy, Douglas; Lin, John C.; Andino, Marlyn Y.; Washburn, Anthony E.; Graff, Emilio; Wygnanski, Israel J.

    2015-01-01

    This paper describes wind tunnel test results from a joint NASA/Boeing research effort to advance active flow control (AFC) technology to enhance aerodynamic efficiency. A full-scale Boeing 757 vertical tail model equipped with sweeping jet actuators was tested at the National Full-Scale Aerodynamics Complex (NFAC) 40- by 80-Foot Wind Tunnel (40x80) at NASA Ames Research Center. The model was tested at a nominal airspeed of 100 knots and across rudder deflections and sideslip angles that covered the vertical tail flight envelope. A successful demonstration of AFC-enhanced vertical tail technology was achieved. A 31- actuator configuration significantly increased side force (by greater than 20%) at a maximum rudder deflection of 30deg. The successful demonstration of this application has cleared the way for a flight demonstration on the Boeing 757 ecoDemonstrator in 2015.

  19. Locally activated Monte Carlo method for long-time-scale simulations

    NASA Astrophysics Data System (ADS)

    Kaukonen, M.; Peräjoki, J.; Nieminen, R. M.; Jungnickel, G.; Frauenheim, Th.

    2000-01-01

    We present a technique for the structural optimization of atom models to study long time relaxation processes involving different time scales. The method takes advantage of the benefits of both the kinetic Monte Carlo (KMC) and the molecular dynamics simulation techniques. In contrast to ordinary KMC, our method allows for an estimation of a true lower limit for the time scale of a relaxation process. The scheme is fairly general in that neither the typical pathways nor the typical metastable states need to be known prior to the simulation. It is independent of the lattice type and the potential which describes the atomic interactions. It is adopted to study systems with structural and/or chemical inhomogeneity which makes it particularly useful for studying growth and diffusion processes in a variety of physical systems, including crystalline bulk, amorphous systems, surfaces with adsorbates, fluids, and interfaces. As a simple illustration we apply the locally activated Monte Carlo to study hydrogen diffusion in diamond.

  20. The effect of local and large-scale environments on nuclear activity and star formation

    NASA Astrophysics Data System (ADS)

    Argudo-Fernández, M.; Shen, S.; Sabater, J.; Duarte Puertas, S.; Verley, S.; Yang, X.

    2016-07-01

    Context. Active galactic nuclei (AGN) are one of the main drivers for the transition from star-forming disk to passive spheroidal galaxies, however, the role of large-scale environment versus one-on-one interactions in triggering different types of AGN is still uncertain. We present a statistical study of the prevalence of the nuclear activity in isolated galaxies and physically bound isolated pairs. Aims: For the purpose of this study we considered optically and radio selected nuclear activity types. We aim to assess the effect of one-on-one interaction on the fraction of AGN and the role of their large-scale environment. Methods: To study the effect of one-on-one interaction on the fraction of AGN in isolated galaxy pairs, we compare these AGN with a sample of isolated galaxies homogeneously selected under the same isolation criterion. We examine the effect of the large-scale environment by comparing isolated systems with control samples of single galaxies and galaxy pairs. We use the tidal strength parameter to quantify the effects of local and large-scale environments. Results: In general we found no difference in the prevalence of optical AGN for the considered samples. For massive galaxies, the fraction of optical AGN in isolated galaxies is slightly higher than that in the control samples. Also, the fraction of passives in high mass isolated galaxies is smaller than in any other sample. Generally, there is no dependence on optical nuclear activity with local environment. On the other hand, we found evidence that radio AGN are strongly affected by the local environment. Conclusions: The optical AGN phenomenon is related to cold gas accretion, while radio AGN are related to hot gas accretion. In this context, there is more cold gas, fuelling the central optical AGN, in isolated systems. Our results are in agreement with a scenario where cold gas accretion by secular evolution is the main driver of optical AGN, while hot gas accretion and one

  1. Bacterial diversity and active biomass in full-scale granular activated carbon filters operated at low water temperatures.

    PubMed

    Kaarela, Outi E; Härkki, Heli A; Palmroth, Marja R T; Tuhkanen, Tuula A

    2015-01-01

    Granular activated carbon (GAC) filtration enhances the removal of natural organic matter and micropollutants in drinking water treatment. Microbial communities in GAC filters contribute to the removal of the biodegradable part of organic matter, and thus help to control microbial regrowth in the distribution system. Our objectives were to investigate bacterial community dynamics, identify the major bacterial groups, and determine the concentration of active bacterial biomass in full-scale GAC filters treating cold (3.7-9.5°C), physicochemically pretreated, and ozonated lake water. Three sampling rounds were conducted to study six GAC filters of different operation times and flow modes in winter, spring, and summer. Total organic carbon results indicated that both the first-step and second-step filters contributed to the removal of organic matter. Length heterogeneity analysis of amplified 16S rRNA genes illustrated that bacterial communities were diverse and considerably stable over time. α-Proteobacteria, β-Proteobacteria, and Nitrospira dominated in all of the GAC filters, although the relative proportion of dominant phylogenetic groups in individual filters differed. The active bacterial biomass accumulation, measured as adenosine triphosphate, was limited due to low temperature, low flux of nutrients, and frequent backwashing. The concentration of active bacterial biomass was not affected by the moderate seasonal temperature variation. In summary, the results provided an insight into the biological component of GAC filtration in cold water temperatures and the operational parameters affecting it. PMID:25242545

  2. The TMS Map Scales with Increased Stimulation Intensity and Muscle Activation.

    PubMed

    van de Ruit, Mark; Grey, Michael J

    2016-01-01

    One way to study cortical organisation, or its reorganisation, is to use transcranial magnetic stimulation (TMS) to construct a map of corticospinal excitability. TMS maps are reported to be acquired with a wide variety of stimulation intensities and levels of muscle activation. Whilst MEPs are known to increase both with stimulation intensity and muscle activation, it remains to be established what the effect of these factors is on the map's centre of gravity (COG), area, volume and shape. Therefore, the objective of this study was to systematically examine the effect of stimulation intensity and muscle activation on these four key map outcome measures. In a first experiment, maps were acquired with a stimulation intensity of 110, 120 and 130% of resting threshold. In a second experiment, maps were acquired at rest and at 5, 10, 20 and 40% of maximum voluntary contraction. Map area and map volume increased with both stimulation intensity (P < 0.01) and muscle activation (P < 0.01). Neither the COG nor the map shape changed with either stimulation intensity or muscle activation (P > 0.09 in all cases). This result indicates the map simply scales with stimulation intensity and muscle activation. PMID:26337508

  3. Molecular mechanism of vinculin activation and nano-scale spatial organization in focal adhesions

    PubMed Central

    Case, Lindsay B.; Baird, Michelle A.; Shtengel, Gleb; Campbell, Sharon L.; Hess, Harald F.; Davidson, Michael W.; Waterman, Clare M.

    2015-01-01

    Focal adhesions (FAs) link the extracellular matrix (ECM) to the actin cytoskeleton to mediate cell adhesion, migration, mechanosensing and signaling. FAs have conserved nanoscale protein organization, suggesting that the position of proteins within FAs regulates their activity and function. Vinculin binds different FA proteins to mediate distinct cellular functions, but how vinculin’s interactions are spatiotemporally organized within FA is unknown. Using interferometric photo-activation localization (iPALM) super-resolution microscopy to assay vinculin nanoscale localization and a FRET biosensor to assay vinculin conformation, we found that upward repositioning within the FA during FA maturation facilitates vinculin activation and mechanical reinforcement of FA. Inactive vinculin localizes to the lower integrin signaling layer in FA by binding to phospho-paxillin. Talin binding activates vinculin and targets active vinculin higher in FA where vinculin can engage retrograde actin flow. Thus, specific protein interactions are spatially segregated within FA at the nano-scale to regulate vinculin activation and function. PMID:26053221

  4. Large scale organization of rat sensorimotor cortex based on a motif of large activation spreads

    PubMed Central

    Frostig, Ron D.; Xiong, Ying; Chen-Bee, Cynthia H.; Kvašňák, Eugen; Stehberg, Jimmy

    2008-01-01

    Parcellation according to function (e.g., visual, somatosensory, auditory, motor) is considered a fundamental property of sensorimotor cortical organization, traditionally defined from cytoarchitectonics and mapping studies relying on peak evoked neuronal activity. In the adult rat, stimulation of single whiskers evokes peak activity at topographically appropriate locations within somatosensory cortex and provides an example of cortical functional specificity. Here, we show that single whisker stimulation also evokes symmetrical areas of supra- and sub-threshold neuronal activation that spread extensively away from peak activity, effectively ignoring cortical borders by spilling deeply into multiple cortical territories of different modalities (auditory, visual and motor), where they were blocked by localized neuronal activity blocker injections and thus ruled out as possibly due to ‘volume conductance’. These symmetrical activity spreads were supported by underlying border-crossing, long-range horizontal connections as confirmed with transection experiments and injections of anterograde neuronal tracer experiments. We found such large evoked activation spreads and their underlying connections irrespective of whisker identity, cortical layer, or axis of recorded responses, thereby revealing a large scale nonspecific organization of sensorimotor cortex based on a motif of large symmetrical activation spreads. Because the large activation spreads and their underlying horizontal connections ignore anatomical borders between cortical modalities, sensorimotor cortex could therefore be viewed as a continuous entity rather than a collection of discrete, delineated unimodal regions – an organization that could co-exist with established specificity of cortical organization and that could serve as a substrate for associative learning, direct multimodal integration and recovery of function following injury. PMID:19052219

  5. Large-scale organization of rat sensorimotor cortex based on a motif of large activation spreads.

    PubMed

    Frostig, Ron D; Xiong, Ying; Chen-Bee, Cynthia H; Kvasnák, Eugen; Stehberg, Jimmy

    2008-12-01

    Parcellation according to function (e.g., visual, somatosensory, auditory, motor) is considered a fundamental property of sensorimotor cortical organization, traditionally defined from cytoarchitectonics and mapping studies relying on peak evoked neuronal activity. In the adult rat, stimulation of single whiskers evokes peak activity at topographically appropriate locations within somatosensory cortex and provides an example of cortical functional specificity. Here, we show that single whisker stimulation also evokes symmetrical areas of suprathreshold and subthreshold neuronal activation that spread extensively away from peak activity, effectively ignoring cortical borders by spilling deeply into multiple cortical territories of different modalities (auditory, visual and motor), where they were blocked by localized neuronal activity blocker injections and thus ruled out as possibly caused by "volume conductance." These symmetrical activity spreads were supported by underlying border-crossing, long-range horizontal connections as confirmed with transection experiments and injections of anterograde neuronal tracer experiments. We found such large evoked activation spreads and their underlying connections regardless of whisker identity, cortical layer, or axis of recorded responses, thereby revealing a large scale nonspecific organization of sensorimotor cortex based on a motif of large symmetrical activation spreads. Because the large activation spreads and their underlying horizontal connections ignore anatomical borders between cortical modalities, sensorimotor cortex could therefore be viewed as a continuous entity rather than a collection of discrete, delineated unimodal regions, an organization that could coexist with established specificity of cortical organization and that could serve as a substrate for associative learning, direct multimodal integration and recovery of function after injury. PMID:19052219

  6. Restricted growth of U-type infectious haematopoietic necrosis virus (IHNV) in rainbow trout cells may be linked to casein kinase II activity

    USGS Publications Warehouse

    Park, J.-W.; Moon, C.H.; Harmache, A.; Wargo, A.R.; Purcell, M.K.; Bremont, M.; Kurath, G.

    2011-01-01

    Previously, we demonstrated that a representative M genogroup type strain of infectious haematopoietic necrosis virus (IHNV) from rainbow trout grows well in rainbow trout-derived RTG-2 cells, but a U genogroup type strain from sockeye salmon has restricted growth, associated with reduced genome replication and mRNA transcription. Here, we analysed further the mechanisms for this growth restriction of U-type IHNV in RTG-2 cells, using strategies that assessed differences in viral genes, host immune regulation and phosphorylation. To determine whether the viral glycoprotein (G) or non-virion (NV) protein was responsible for the growth restriction, four recombinant IHNV viruses were generated in which the G gene of an infectious IHNV clone was replaced by the G gene of U- or M-type IHNV and the NV gene was replaced by NV of U- or M-type IHNV. There was no significant difference in the growth of these recombinants in RTG-2 cells, indicating that G and NV proteins are not major factors responsible for the differential growth of the U- and M-type strains. Poly I:C pretreatment of RTG-2 cells suppressed the growth of both U- and M-type IHNV, although the M virus continued to replicate at a reduced level. Both viruses induced type 1 interferon (IFN1) and the IFN1 stimulated gene Mx1, but the expression levels in M-infected cells were significantly higher than in U-infected cells and an inhibitor of the IFN1-inducible protein kinase PKR, 2-aminopurine (2-AP), did not affect the growth of U- or M-type IHNV in RTG-2 cells. These data did not indicate a role for the IFN1 system in the restricted growth of U-type IHNV in RTG-2 cells. Prediction of kinase-specific phosphorylation sites in the viral phosphoprotein (P) using the NetPhosK program revealed differences between U- and M-type P genes at five phosphorylation sites. Pretreatment of RTG-2 cells with a PKC inhibitor or a p38MAPK inhibitor did not affect the growth of the U- and M-type viruses. However, 100 μm of the

  7. MHC-restricted recognition of immunogenic T cell epitopes of pertussis toxin reveals determinants in man distinct from the ADP-ribosylase active site

    PubMed Central

    1988-01-01

    The S1 subunit of Pertussis toxin (PT) is responsible for the reactogenicity and in part the immunogenicity of Bordetella pertussis vaccine. The critical residues associated with the immunomodulatory effects of PT were located around Glu140 in the S1 subunit. In man, T cell responses to PT are directed at S1 peptides distinct from Glu140. Two such epitopes, p64-75 and p151-161, are immunogenic in a panel of individuals covering a wide range of HLA genotypes. The response to PT peptides is HLA class II restricted. The response to p64-75 is blocked by an anti-HLA-DQ mAb, while that to p151-161 is blocked by an anti-HLA- DR mAb. These findings may allow for the development of a B. pertussis vaccine free from reactogenicity. PMID:2460578

  8. Unconventional critical activated scaling of two-dimensional quantum spin glasses

    NASA Astrophysics Data System (ADS)

    Matoz-Fernandez, D. A.; Romá, F.

    2016-07-01

    We study the critical behavior of two-dimensional short-range quantum spin glasses by numerical simulations. Using a parallel tempering algorithm, we calculate the Binder cumulant for the Ising spin glass in a transverse magnetic field with two different short-range bond distributions, the bimodal and the Gaussian ones. Through an exhaustive finite-size analysis, we show that the cumulant probably follows an unconventional activated scaling, which we interpret as new evidence supporting the hypothesis that the quantum critical behavior is governed by an infinite randomness fixed point.

  9. Virulent Mycobacterium fortuitum restricts NO production by a gamma interferon-activated J774 cell line and phagosome-lysosome fusion.

    PubMed

    Da Silva, Tânia Regina Marques; De Freitas, Juliana Ribeiro; Silva, Queilan Chagas; Figueira, Cláudio Pereira; Roxo, Eliana; Leão, Sylvia Cardoso; De Freitas, Luiz Antônio Rodrigues; Veras, Patrícia Sampaio Tavares

    2002-10-01

    The virulence of different isolates of Mycobacterium has been associated with two morphologically distinguishable colonial variants: opaque (SmOp) and transparent (SmTr). In this report we used an in vitro assay to compare macrophage (Mphi) responses to SmOp and SmTr Mycobacterium fortuitum variants, taking advantage of the fact that these variants were derived from the same isolate. Cells preactivated or not with gamma interferon (IFN-gamma) were infected with SmOp or SmTr M. fortuitum. We showed that SmOp and SmTr induced different levels of nitric oxide (NO) production by IFN-gamma-stimulated Mphi. Indeed, the amount of IFN-gamma-induced NO production by J774 cells was 4.8 to 9.0 times higher by SmOp (23.1 to 37.7 micro M) compared to SmTr infection (3.9 to 4.8 micro M) (P = 0.0332), indicating that virulent SmTr bacilli restricted NO production. In addition, IFN-gamma-induced NO production by Mphi was higher when correlated with reduction of only avirulent SmOp bacillus viability. SNAP (S-nitroso-N-acetyl-DL-penicillamine)-induced NO production did not modify SmTr viability, indicating its resistance to nitrogen radicals. Electron microscopy studies were performed to evaluate the capacity of phagosomes to fuse with lysosomes labeled with bovine serum albumin-colloidal gold particles. By 24 h postinfection, 69% more phagosome-containing SmOp variant had fused with lysosomes compared to the SmTr-induced phagosomes. In conclusion, these data indicate that virulent SmTr bacilli may escape host defense by restricting IFN-gamma-induced NO production, resisting nitrogen toxic radicals, and limiting phagosome fusion with lysosomes. PMID:12228291

  10. Validation of the Italian version of Mini-ICF-APP, a short instrument for rating activity and participation restrictions in psychiatric disorders.

    PubMed

    Balestrieri, M; Isola, M; Bonn, R; Tam, T; Vio, A; Linden, M; Maso, E

    2013-03-01

    Aims. The assessment of limitations in social capacities can be done with the Mini-ICF-APP, a rating scale built in reference to the International Classification of Functioning, Disability and Health (ICF). The aim of this study was to assess the reliability and the convergent validity of the Italian version of this scale. Methods. We recruited 120 consecutive patients diagnosed with schizophrenia, major depression, bipolar I disorder and anxiety disorders. Included measures were the Brief Psychiatric Rating Scale (BPRS), the Clinical Global Impression Scale (CGI-S), the Personal and Social Performance Scale (PSP) and the Social and Occupational Functioning Assessment Scale (SOFAS). Results. The median CGI-S and BPRS scores were 5 and 16.5. Mean Mini-ICF-APP total score was 18.1. Schizophrenics' Mini-ICF-APP score was higher, while that of anxious patients was lower than in the other diagnoses. Intra-class correlations (ICC) revealed a significant inter-rater agreement for total score (ICC 0.987) and for each item of the Mini-ICF-APP. The test-retest agreement was also highly significant (ICC 0.993). The total score of the Mini-ICF-APP obtained good negative correlations with PSP (r s = -0.767) and with SOFAS scores (r s = -0.790). The distribution items of the Mini-ICF-APP showed some skewness, indicating that self-care (item 12) and mobility (item 13) were amply preserved in most patients. The Mini-ICF-APP total score was significantly correlated with both CGI-S (r s = 0.777) and BPRS (r s = 0.729). Conclusions. As a short instrument, the Mini-ICF-APP scale seems to be well suited to everyday psychiatric practice as a means of monitoring changes in psychosocial functioning, in particular in schizophrenic patients. PMID:22989494

  11. Field-Scale Stable-Isotope Probing of Active Methanotrophs in a Landfill-Cover Soil

    NASA Astrophysics Data System (ADS)

    Schroth, M. H.; Henneberger, R.; Chiri, E.

    2012-12-01

    The greenhouse gas methane (CH4) is an important contributor to global climate change. While its atmospheric concentration is increasing, a large portion of produced CH4 never reaches the atmosphere, but is consumed by aerobic methane-oxidizing bacteria (MOB). The latter are ubiquitous in soils and utilize CH4 as sole source of energy and carbon. Among other methods, MOB may be differentiated based on characteristic phospholipid fatty acids (PLFA). Stable-isotope probing (SIP) on PLFA has been widely applied to identify active members of MOB communities in laboratory incubation studies, but results are often difficult to extrapolate to the field. Thus, novel field-scale approaches are needed to link activity and identity of MOB in their natural environment. We present results of field experiments in which we combined PLFA-SIP with gas push-pull tests (GPPTs) to label active MOB at the field-scale while simultaneously quantifying CH4 oxidation activity. During a SIP-GPPT, a mixture of reactive (here 13CH4, O2) and non-reactive tracer gases (e.g., Ar, Ne, He) is injected into the soil at a location of interest. Thereafter, gas flow is reversed and the gas mixture diluted with soil air is extracted from the same location and sampled periodically. Rate constants for CH4 oxidation can be calculated by analyzing breakthrough curves of 13CH4 and a suitable non-reactive tracer gas. SIP-GPPTs were performed in a landfill-cover soil, and feasibility of this novel approach was tested at several locations along a gradient of MOB activity and soil temperature. Soil samples were collected before and after SIP-GPPTs, total PLFA were extracted, and incorporation of 13C in the polar lipid fraction was analyzed. Potential CH4 oxidation rates derived from SIP-GPPTs were similar to those derived from regular GPPTs (using unlabeled CH4) performed at the same locations prior to SIP-GPPTs, indicating that application of 13CH4 did not adversely affect bacterial CH4 oxidation rates. Rates

  12. An activated sludge model based on activated sludge model number 3 for full-scale wastewater treatment plant simulation.

    PubMed

    Fan, Ji; Lu, Shu-Guang; Qiu, Zhao-fu; Wang, Xiao-Xia; Li, Wen-Zhen

    2009-06-01

    A modified model based on the activated sludge model no. 3 was established to simulate a full-scale municipal wastewater treatment plant in Shanghai, China. The activated sludge model no. 3 was modified to describe the simultaneous storage and growth processes occurring in activated sludge systems under aerobic and anoxic conditions. The mechanism of soluble microbial product formation and degradation by microorganisms was considered in this proposed model. Three months simulation was conducted including soluble chemical oxygen demand, NH4(+)-N, NO(X)(-)-N and T-N parameters, and compared with measured data from the Quyang wastewater treatment plant. Results indicated that the calculated effluent chemical oxygen demand and NH4(+)-N using this proposed model were in good agreement with the measured data. Results also showed that besides inert soluble organic matter contributing to the effluent chemical oxygen demand, soluble microbial products played an important part in the effluent chemical oxygen demand and, therefore, demonstrated that these products composed an important portion of effluent soluble chemical oxygen demand in wastewater treatment plants and should not be neglected. PMID:19705601

  13. Failure and deformation mechanisms at macro- and nano-scales of alkali activated clay

    NASA Astrophysics Data System (ADS)

    Sekhar Das, Pradip; Bhattacharya, Manjima; Chanda, Dipak Kr; Dalui, Srikanta; Acharya, Saikat; Ghosh, Swapankumar; Mukhopadhyay, Anoop Kumar

    2016-06-01

    Here we report two qualitative models on failure and deformation mechanisms at macro- and nano-scales of alkali activated clay (AACL), a material of extraordinary importance as a low cost building material. The models were based on experimental data of compressive failure and nanoindentation response of the AACL materials. A 420% improvement in compressive strength (σ c) of the AACL was achieved after 28 days (d) of curing at room temperature and it correlated well with the decrements in the residual alkali and pH concentrations with the increase in curing time. Based on extensive post-mortem FE-SEM examinations, a schematic model for the compressive failure mechanism of AACL was proposed. In addition, the nanoindentation results of AACL provided the first ever experimental evidence of the presence of nano-scale plasticity and a nano-scale contact deformation resistance that increased with the applied load. These results meant the development of a unique strain tolerant microstructure in the AACL of Indian origin. The implications of these new observations were discussed in terms of a qualitative model based on the deformation of layered clay structure.

  14. Active Self-Testing Noise Measurement Sensors for Large-Scale Environmental Sensor Networks

    PubMed Central

    Domínguez, Federico; Cuong, Nguyen The; Reinoso, Felipe; Touhafi, Abdellah; Steenhaut, Kris

    2013-01-01

    Large-scale noise pollution sensor networks consist of hundreds of spatially distributed microphones that measure environmental noise. These networks provide historical and real-time environmental data to citizens and decision makers and are therefore a key technology to steer environmental policy. However, the high cost of certified environmental microphone sensors render large-scale environmental networks prohibitively expensive. Several environmental network projects have started using off-the-shelf low-cost microphone sensors to reduce their costs, but these sensors have higher failure rates and produce lower quality data. To offset this disadvantage, we developed a low-cost noise sensor that actively checks its condition and indirectly the integrity of the data it produces. The main design concept is to embed a 13 mm speaker in the noise sensor casing and, by regularly scheduling a frequency sweep, estimate the evolution of the microphone's frequency response over time. This paper presents our noise sensor's hardware and software design together with the results of a test deployment in a large-scale environmental network in Belgium. Our middle-range-value sensor (around €50) effectively detected all experienced malfunctions, in laboratory tests and outdoor deployments, with a few false positives. Future improvements could further lower the cost of our sensor below €10. PMID:24351634

  15. Brain activity mapping at multiple scales with silicon microprobes containing 1,024 electrodes

    PubMed Central

    Shobe, Justin L.; Claar, Leslie D.; Parhami, Sepideh; Bakhurin, Konstantin I.

    2015-01-01

    The coordinated activity of neural ensembles across multiple interconnected regions has been challenging to study in the mammalian brain with cellular resolution using conventional recording tools. For instance, neural systems regulating learned behaviors often encompass multiple distinct structures that span the brain. To address this challenge we developed a three-dimensional (3D) silicon microprobe capable of simultaneously measuring extracellular spike and local field potential activity from 1,024 electrodes. The microprobe geometry can be precisely configured during assembly to target virtually any combination of four spatially distinct neuroanatomical planes. Here we report on the operation of such a device built for high-throughput monitoring of neural signals in the orbitofrontal cortex and several nuclei in the basal ganglia. We perform analysis on systems-level dynamics and correlations during periods of conditioned behavioral responding and rest, demonstrating the technology's ability to reveal functional organization at multiple scales in parallel in the mouse brain. PMID:26133801

  16. License restrictions at Barnwell

    SciTech Connect

    Autry, V.R.

    1991-12-31

    The State of South Carolina was delegated the authority by the US Nuclear Regulatory Commission to regulate the receipt, possession, use and disposal of radioactive material as an Agreement State. Since 1970, the state has been the principal regulatory authority for the Barnwell Low-Level Waste Disposal Facility operated by Chem-Nuclear Systems, Inc. The radioactive material license issued authorizing the receipt and disposal of low-level waste contains numerous restrictions to ensure environmental protection and compliance with shallow land disposal performance criteria. Low-level waste has evolved from minimally contaminated items to complex waste streams containing high concentrations of radionuclides and processing chemicals which necessitated these restrictions. Additionally, some waste with their specific radionuclides and concentration levels, many classified as low-level radioactive waste, are not appropriate for shallow land disposal unless additional precautions are taken. This paper will represent a number of these restrictions, the rationale for them, and how they are being dealt with at the Barnwell disposal facility.

  17. Quantity-activity relationship of denitrifying bacteria and environmental scaling in streams of a forested watershed

    NASA Astrophysics Data System (ADS)

    O'Connor, Ben L.; Hondzo, Miki; Dobraca, Dina; Lapara, Timothy M.; Finlay, Jacques C.; Brezonik, Patrick L.

    2006-12-01

    The spatial variability of subreach denitrification rates in streams was evaluated with respect to controlling environmental conditions, molecular examination of denitrifying bacteria, and dimensional analysis. Denitrification activities ranged from 0 and 800 ng-N gsed-1 d-1 with large variations observed within short distances (<50 m) along stream reaches. A log-normal probability distribution described the range in denitrification activities and was used to define low (16% of the probability distribution), medium (68%), and high (16%) denitrification potential groups. Denitrifying bacteria were quantified using a competitive polymerase chain reaction (cPCR) technique that amplified the nirK gene that encodes for nitrite reductase. Results showed a range of nirK quantities from 103 to 107 gene-copy-number gsed-1. A nonparametric statistical test showed no significant difference in nirK quantities among stream reaches, but revealed that samples with a high denitrification potential had significantly higher nirK quantities. Denitrification activity was positively correlated with nirK quantities with scatter in the data that can be attributed to varying environmental conditions along stream reaches. Dimensional analysis was used to evaluate denitrification activities according to environmental variables that describe fluid-flow properties, nitrate and organic material quantities, and dissolved oxygen flux. Buckingham's pi theorem was used to generate dimensionless groupings and field data were used to determine scaling parameters. The resulting expressions between dimensionless NO3- flux and dimensionless groupings of environmental variables showed consistent scaling, which indicates that the subreach variability in denitrification rates can be predicted by the controlling physical, chemical, and microbiological conditions.

  18. Quantity-activity relationship of denitrifying bacteria and environmental scaling in streams of a forested watershed

    USGS Publications Warehouse

    O'Connor, B.L.; Hondzo, Miki; Dobraca, D.; LaPara, T.M.; Finlay, J.A.; Brezonik, P.L.

    2006-01-01

    The spatial variability of subreach denitrification rates in streams was evaluated with respect to controlling environmental conditions, molecular examination of denitrifying bacteria, and dimensional analysis. Denitrification activities ranged from 0 and 800 ng-N gsed-1 d-1 with large variations observed within short distances (<50 m) along stream reaches. A log-normal probability distribution described the range in denitrification activities and was used to define low (16% of the probability distributibn), medium (68%), and high (16%) denitrification potential groups. Denitrifying bacteria were quantified using a competitive polymerase chain reaction (cPCR) technique that amplified the nirK gene that encodes for nitrite reductase. Results showed a range of nirK quantities from 103 to 107 gene-copy-number gsed.-1 A nonparametric statistical test showed no significant difference in nirK quantifies among stream reaches, but revealed that samples with a high denitrification potential had significantly higher nirK quantities. Denitrification activity was positively correlated with nirK quantities with scatter in the data that can be attributed to varying environmental conditions along stream reaches. Dimensional analysis was used to evaluate denitrification activities according to environmental variables that describe fluid-flow properties, nitrate and organic material quantities, and dissolved oxygen flux. Buckingham's pi theorem was used to generate dimensionless groupings and field data were used to determine scaling parameters. The resulting expressions between dimensionless NO3- flux and dimensionless groupings of environmental variables showed consistent scaling, which indicates that the subreach variability in denitrification rates can be predicted by the controlling physical, chemical, and microbiological conditions. Copyright 2006 by the American Geophysical Union.

  19. A Validation and Reliability Study of the Physical Activity and Healthy Food Efficacy Scale for Children (PAHFE)

    ERIC Educational Resources Information Center

    Perry, Christina M.; De Ayala, R. J.; Lebow, Ryan; Hayden, Emily

    2008-01-01

    The purpose of this study was to obtain validity evidence for the Physical Activity and Healthy Food Efficacy Scale for Children (PAHFE). Construct validity evidence identifies four subscales: Goal-Setting for Physical Activity, Goal-Setting for Healthy Food Choices, Decision-Making for Physical Activity, and Decision-Making for Healthy Food…

  20. Fine-scale differences in diel activity among nocturnal freshwater planarias (Platyhelminthes: Tricladida)

    PubMed Central

    2011-01-01

    Background Although most freshwater planarias are well known photonegative organisms, their diel rhythms have never been quantified. Differences in daily activity rhythms may be particularly important for temperate-climate, freshwater planarias, which tend to overlap considerably in spatial distribution and trophic requirements. Methods Activity of stress-free, individually tested young adults of three common planarian species was recorded at 3-h intervals in a 10-d experiment under natural sunlight and photoperiod during autumnal equinox (D:L ~12:12). Individual activity status was averaged over the 10-d experiment, each tested individual thus serving as a true replicate. Twelve individuals per species were tested. Food was provided every 36 h, resulting in alternating day- and nighttime feeding events. Activity during the first post-feeding h was recorded and analyzed separately. Statistical procedures included ANOVAs, correlations, and second-order analyses of angles. Results Dugesia (= Girardia) tigrina Girard 1850 exhibited clear nocturnal behavior, Dugesia (= Schmidtea) polychroa Schmidt 1861 was predominantly but not exclusively nocturnal, and Polycelis tenuis Ijima 1884 was relatively more active from midnight through noon. Species-specific activity peaks were statistically similar, with peaks at dawn for P. tenuis and just before midnight for the two dugesiids; however, D. tigrina was comparatively more active in the early night hours, while D. polychroa was more active than D. tigrina during daytime. D. tigrina also responded less readily to daytime food addition. P. tenuis remained poorly active and unresponsive throughout the experiment. Individual variability in diel behavior was highest for D. polychroa and lowest for D. tigrina. P. tenuis's general low degree of activity and late activity peak in the experiment may be related to a strong reliance on external stimuli. Conclusions The tested species are mainly nocturnal, consistent with their

  1. Observations of Small-scale IRIS Bombs (Reconnection Events) in an Evolving Active Region

    NASA Astrophysics Data System (ADS)

    Madsen, C. A.; Tian, H.; DeLuca, E. E.

    2015-12-01

    We present the first Interface Region Imaging Spectrograph (IRIS) observations of small-scale bombs evolving with their host active region. Bombs appear most clearly in the IRIS 1330 Å and 1400 Å slit-jaw images as small (~1 arcsec), compact, intense brightenings at transition region temperatures. Their NUV/FUV emission spectra exhibit dramatic line splitting and strong absorption features indicative of bidirectional flows from magnetic reconnection embedded deep within the cool lower solar atmosphere. The bombs may contribute significantly to the heating of the solar atmosphere in active regions; however, it's unclear how prevalent the bombs are throughout the lifetime of an active region. Using a semi-automated detection method, we locate bombs within AR 11850 over the course of four observations from 06:00 UT on September 25, 2013 until 11:30 UT the next day. The active region is first observed in an emerging phase and rapidly grows into a mature active region with well-developed sunspots. The bomb occurrence rate drops dramatically as the active region fully emerges. We also find that the bombs fall into two distinct populations: one appears largely during active region emergence and contains a majority of the bombs, while the other population is present regardless of active region age. The first population of bombs is typically found embedded in the low-lying loops prominent in the young active region. Furthermore, we use Solar Dynamics Observatory/Helioseismic and Magnetic Imager (SDO/HMI) line-of-sight magnetograms to show that the bombs associated with the first population occur at the boundaries between the upward and downward flux of small, isolated bipolar regions. These regions dissipate as the active region emerges and reconfigures its magnetic field into two large network patches of upward and downward flux with a clear inversion line. The second, smaller population of bombs usually occurs far from the active region loop structures in the plage and

  2. Coronal holes, large-scale magnetic field, and activity complexes in solar cycle 23

    NASA Astrophysics Data System (ADS)

    Tavastsherna, K. S.; Polyakow, E. V.

    2014-12-01

    A correlation among coronal holes (CH), a large-scale magnetic field (LMF), and activity complexes (AC) is studied in this work for 1997-2007 with the use of a coronal hole series obtained from observations at the Kitt Peak Observatory in the HeI 10830 Å line in 1975-2003 and SOHO/EIT-195 Å in 1996-2012 (Tlatov et al., 2014), synoptic Hα charts from Kislovodsk Mountain Astonomical Station, and the catalog of AC cores (Yazev, 2012). From the imposition of CH boundaries on Hα charts, which characterize the positions of neutral lines of the radial components of a large-scale solar magnetic field, it turns out that 70% of CH are located in unipolar regions of their sign during the above period, 10% are in the region of an opposite sign, and 20% are mainly very large CH, which are often crossed by the neutral lines of several unipolar regions. Data on mutual arrangement of CH and AC cores were obtained. It was shown that only some activity comples cores have genetic relationships with CH.

  3. Quantifying the metabolic activities of human-associated microbial communities across multiple ecological scales

    PubMed Central

    Maurice, Corinne Ferrier; Turnbaugh, Peter James

    2013-01-01

    Humans are home to complex microbial communities, whose aggregate genomes and their encoded metabolic activities are referred to as the human microbiome. Recently, researchers have begun to appreciate that different human body habitats and the activities of their resident microorganisms can be better understood in ecological terms, as a range of spatial scales encompassing single cells, guilds of microorganisms responsive to a similar substrate, microbial communities, body habitats, and host populations. However, the bulk of the work to date has focused on studies of culturable microorganisms in isolation or on DNA sequencing-based surveys of microbial diversity in small to moderately sized cohorts of individuals. Here, we discuss recent work that highlights the potential for assessing the human microbiome at a range of spatial scales, and for developing novel techniques that bridge multiple levels: for example, through the combination of single cell methods and metagenomic sequencing. These studies promise to not only provide a much-needed epidemiological and ecological context for mechanistic studies of culturable and genetically tractable microorganisms, but may also lead to the discovery of fundamental rules that govern the assembly and function of host-associated microbial communities. PMID:23550823

  4. Ignition dynamics and activation energies of metallic thermites: From nano- to micron-scale particulate composites

    SciTech Connect

    Hunt, Emily M.; Pantoya, Michelle L.

    2005-08-01

    Ignition behaviors associated with nano- and micron-scale particulate composite thermites were studied experimentally and modeled theoretically. The experimental analysis utilized a CO{sub 2} laser ignition apparatus to ignite the front surface of compacted nickel (Ni) and aluminum (Al) pellets at varying heating rates. Ignition delay time and ignition temperature as a function of both Ni and Al particle size were measured using high-speed imaging and microthermocouples. The apparent activation energy was determined from this data using a Kissinger isoconversion method. This study shows that the activation energy is significantly lower for nano- compared with micron-scale particulate media (i.e., as low as 17.4 compared with 162.5 kJ/mol, respectively). Two separate Arrhenius-type mathematical models were developed that describe ignition in the nano- and the micron-composite thermites. The micron-composite model is based on a heat balance while the nanocomposite model incorporates the energy of phase transformation in the alumina shell theorized to be an initiating step in the solid-solid diffusion reaction and uniquely appreciable in nanoparticle media. These models were found to describe the ignition of the Ni/Al alloy for a wide range of heating rates.

  5. Ignition dynamics and activation energies of metallic thermites: From nano- to micron-scale particulate composites

    NASA Astrophysics Data System (ADS)

    Hunt, Emily M.; Pantoya, Michelle L.

    2005-08-01

    Ignition behaviors associated with nano- and micron-scale particulate composite thermites were studied experimentally and modeled theoretically. The experimental analysis utilized a CO2 laser ignition apparatus to ignite the front surface of compacted nickel (Ni) and aluminum (Al) pellets at varying heating rates. Ignition delay time and ignition temperature as a function of both Ni and Al particle size were measured using high-speed imaging and microthermocouples. The apparent activation energy was determined from this data using a Kissinger isoconversion method. This study shows that the activation energy is significantly lower for nano- compared with micron-scale particulate media (i.e., as low as 17.4 compared with 162.5kJ /mol, respectively). Two separate Arrhenius-type mathematical models were developed that describe ignition in the nano- and the micron-composite thermites. The micron-composite model is based on a heat balance while the nanocomposite model incorporates the energy of phase transformation in the alumina shell theorized to be an initiating step in the solid-solid diffusion reaction and uniquely appreciable in nanoparticle media. These models were found to describe the ignition of the Ni /Al alloy for a wide range of heating rates.

  6. The Issue of Range Restriction in Bookmark Standard Setting

    ERIC Educational Resources Information Center

    Wyse, Adam E.

    2015-01-01

    This article uses data from a large-scale assessment program to illustrate the potential issue of range restriction with the Bookmark method in the context of trying to set cut scores to closely align with a set of college and career readiness benchmarks. Analyses indicated that range restriction issues existed across different response…

  7. Laser active imaging-guided anti-tank missile system small-scale integration design

    NASA Astrophysics Data System (ADS)

    Yan, Mingliang; Shan, Xiangqian; Qu, Zhou

    2010-10-01

    At present, the domestic and international third-generation anti-tank missiles, laser-guided missiles are mostly divided into active laser-guided and laser semi-active guidance, this guidance system, there are vulnerable to electronic interference, can not be fully realized after launching deficiencies. Article based on this, an in-depth understanding of imaging-guided laser-active working principle, based on the pairs of third-generation anti-tank missile guidance system, boldly proposed to improve the anti-tank missiles, laser-active small-scale integration of imaging guidance system design, the main purpose is to improve a certain type of The optical target missile, TV angle measurement, laser-guided instruction transmission means, so that anti-tank missiles to achieve forward-looking, the next obstacle avoidance TV and multi-functional integration of the entire after launching smart missiles, and in theory be able to study the new antitank missiles play a certain reference.

  8. T & I--Drafting, Reading the Architect's Scale. Kit No. 16. Instructor's Manual [and] Student Learning Activity Guide.

    ERIC Educational Resources Information Center

    Jones, Philip

    An instructor's manual and student activity guide on reading the architect's scale and the metric scale are provided in this set of prevocational education materials which focuses on the vocational area of trade and industry (drafting). (This set of materials is one of ninety-two prevocational education sets arranged around a cluster of seven…

  9. Synthesis and biological activities of tricyclic conformationally restricted tetrahydropyrido annulated furo[2,3-d]pyrimidines as inhibitors of dihydrofolate reductases.

    PubMed

    Gangjee, A; Elzein, E; Queener, S F; McGuire, J J

    1998-04-23

    The synthesis of seven 2,4-diamino-5,6,7,8-tetrahydro-7-substituted pyrido[4',3':4,5]furo[2,3-d]pyrimidines 1-6 are reported as nonclassical antifolate inhibitors of dihydrofolate reductase (DHFR) and compound 7 as a classical antifolate inhibitor of tumor cells in culture. The compounds were designed as conformationally restricted analogues of trimetrexate. The synthesis was accomplished from the cyclocondensation of 3-bromo-4-piperidone with 2, 4-diamino-6-hydroxypyrimidine to afford regiospecifically 2, 4-diamino-5,6,7,8-tetrahydropyrido[4',3':4,5]furo[2, 3-d]pyrimidine-7-hydrobromide (16). This in turn was alkylated with the appropriate benzyl halide to afford the target compounds 1-6. The classical antifolate 7 utilized 4-(chloromethyl)benzoyl-l-glutamic acid diethyl ester (17) instead of the benzyl halide for alkylation, followed by saponification to afford 7. Compounds 1-6 showed moderate inhibitory potency against DHFR from Pneumocystis carinii, Toxoplasma gondii, Mycobacterium avium, and rat liver. The classical analogue 7 was 88-fold more potent against M. avium DHFR than against rat liver DHFR. The classical analogue was also inhibitory against the growth of tumor cells, CCRF-CEM, and FaDu, in culture. PMID:9554874

  10. Suppression of osteoclastic activities by calcitonin in the scales of goldfish (freshwater teleost) and nibbler fish (seawater teleost).

    PubMed

    Suzuki, N; Suzuki, T; Kurokawa, T

    2000-01-01

    Using a tartrate-resistant acid phosphatase (TRACP) activity, the effects of calcitonin (CT) and estradiol-17beta(E(2)) on osteoclastic activities in cultured scales of goldfish (freshwater fish) and nibbler fish (seawater fish) were examined. In mature male and female goldfish, scales were collected and incubated in Earle's minimun essential medium (MEM) supplemented with either CT (100 ng/ml) or E(2) (100 ng/ml). In both sexes, CT suppressed TRACP activities in the scales, whereas E(2) increased them. When CT (100 ng/ml) and E(2) (100 ng/ml) were added simultaneously to MEM, TRACP activities in the scales did not change as compared with the control. Similar results were obtained with the scales of female nibbler fish. In goldfish, furthermore, the activation of scale TRACP by E(2) was suppressed, depending on CT concentrations (100 pg/ml to 1 microg/ml). In fish reproduction, this function of CT may be useful to protect scales from excess degradation of calcium at vitellogenesis. PMID:10704727

  11. Physics of active flow control around a pillar at the micro scale

    NASA Astrophysics Data System (ADS)

    Jung, Junkyu

    2011-12-01

    The use of microchannels for heat transfer enhancement has been studied for the last few decades. To take full advantage of a microchannel, various approaches such as two-phase flow, enhanced heat transfer surface, and flow boiling across pin fins entrenched inside a microchannel have been studied. Among them, micro pin fins heat exchangers, similar to their conventional counterparts have been seriously considered due to their superior heat removal performance throughout the extended surface area. In addition, an early transition to turbulent flow via micro pin fins is believed to improve heat transfer at the micro scale. Therefore, the aim of this study is to extend fundamental knowledge of flow around a micro pin fin with and without active flow. The flow field around a micro pillar was measured using micro particle image velocimetry (muPIV), and the turbulent kinetic energy (TKE ) of the flow was measured to quantify flow mixing around the micro pillar. It was found that an early transition to an unsteady flow was not achieved through the micro pillar due to the inherently small height-to-diameter ratio of the pillar, and the corresponding TKE around the micro pillar was not significant in a quasi-steady flow regime. Active flow control via a steady jet was employed through the slit on the micro pillar surface, where the circumferential location of the slit was varied. The velocity field as well as the TKE of the controlled flow was measured to determine the effect of active flow control at the micro scale. Parametric studies were performed and comparison of the various momentum coefficient, flow regime, and the azimuthal location of the control jet were conducted. Suction was introduced as alternative control scheme, and compared to a steady jet. It was found that mixing was significantly enhanced through the steady jet whereas suction was not successful with same momentum coefficients.

  12. Ice stream activity scaled to ice sheet volume during Laurentide Ice Sheet deglaciation.

    PubMed

    Stokes, C R; Margold, M; Clark, C D; Tarasov, L

    2016-02-18

    The contribution of the Greenland and West Antarctic ice sheets to sea level has increased in recent decades, largely owing to the thinning and retreat of outlet glaciers and ice streams. This dynamic loss is a serious concern, with some modelling studies suggesting that the collapse of a major ice sheet could be imminent or potentially underway in West Antarctica, but others predicting a more limited response. A major problem is that observations used to initialize and calibrate models typically span only a few decades, and, at the ice-sheet scale, it is unclear how the entire drainage network of ice streams evolves over longer timescales. This represents one of the largest sources of uncertainty when predicting the contributions of ice sheets to sea-level rise. A key question is whether ice streams might increase and sustain rates of mass loss over centuries or millennia, beyond those expected for a given ocean-climate forcing. Here we reconstruct the activity of 117 ice streams that operated at various times during deglaciation of the Laurentide Ice Sheet (from about 22,000 to 7,000 years ago) and show that as they activated and deactivated in different locations, their overall number decreased, they occupied a progressively smaller percentage of the ice sheet perimeter and their total discharge decreased. The underlying geology and topography clearly influenced ice stream activity, but--at the ice-sheet scale--their drainage network adjusted and was linked to changes in ice sheet volume. It is unclear whether these findings can be directly translated to modern ice sheets. However, contrary to the view that sees ice streams as unstable entities that can accelerate ice-sheet deglaciation, we conclude that ice streams exerted progressively less influence on ice sheet mass balance during the retreat of the Laurentide Ice Sheet. PMID:26887494

  13. Survival and catabolic activity of natural and genetically engineered bacteria in a laboratory-scale activated-sludge unit

    SciTech Connect

    McClure, N.C.; Fry, J.C.; Weightman, A.J. )

    1991-02-01

    The survival of selected naturally occurring and genetically engineered bacteria in a fully functional laboratory-scale activated-sludge unit (ASU) was investigated. The effect of the presence of 3-chlorobenzoate (3CB) on the survival of Pseudomonas putida UWC1, with or without a chimeric plasmid, pD10, which encodes 3CB catabolism, was determined. P. putida UWC1(pD10) did not enhance 3CB breakdown in the ASU, even following inoculation at a high concentration (3 x 10(8) CFU/ml). The emergence of a natural, 3CB-degrading population appeared to have a detrimental effect on the survival of strain UWC1 in the ASU. The fate of two 3CB-utilizing bacteria, derived from activated-sludge microflora, was studied in experiments in which these strains were inoculated into the ASU. Both strains, AS2, an unmanipulated natural isolate which flocculated readily in liquid media, and P. putida ASR2.8, a transconjugant containing the recombinant plasmid pD10, survived for long periods in the ASU and enhanced 3CB breakdown at 15 degrees C. The results reported in this paper illustrate the importance of choosing strains which are well adapted to environmental conditions if the use of microbial inoculants for the breakdown of target pollutants is to be successful.

  14. Performance of a novel wafer scale CMOS active pixel sensor for bio-medical imaging.

    PubMed

    Esposito, M; Anaxagoras, T; Konstantinidis, A C; Zheng, Y; Speller, R D; Evans, P M; Allinson, N M; Wells, K

    2014-07-01

    Recently CMOS active pixels sensors (APSs) have become a valuable alternative to amorphous silicon and selenium flat panel imagers (FPIs) in bio-medical imaging applications. CMOS APSs can now be scaled up to the standard 20 cm diameter wafer size by means of a reticle stitching block process. However, despite wafer scale CMOS APS being monolithic, sources of non-uniformity of response and regional variations can persist representing a significant challenge for wafer scale sensor response. Non-uniformity of stitched sensors can arise from a number of factors related to the manufacturing process, including variation of amplification, variation between readout components, wafer defects and process variations across the wafer due to manufacturing processes. This paper reports on an investigation into the spatial non-uniformity and regional variations of a wafer scale stitched CMOS APS. For the first time a per-pixel analysis of the electro-optical performance of a wafer CMOS APS is presented, to address inhomogeneity issues arising from the stitching techniques used to manufacture wafer scale sensors. A complete model of the signal generation in the pixel array has been provided and proved capable of accounting for noise and gain variations across the pixel array. This novel analysis leads to readout noise and conversion gain being evaluated at pixel level, stitching block level and in regions of interest, resulting in a coefficient of variation ⩽1.9%. The uniformity of the image quality performance has been further investigated in a typical x-ray application, i.e. mammography, showing a uniformity in terms of CNR among the highest when compared with mammography detectors commonly used in clinical practice. Finally, in order to compare the detection capability of this novel APS with the technology currently used (i.e. FPIs), theoretical evaluation of the detection quantum efficiency (DQE) at zero-frequency has been performed, resulting in a higher DQE for this

  15. Proton-synchrotron radiation of large-scale jets in active galactic nuclei

    NASA Astrophysics Data System (ADS)

    Aharonian, F. A.

    2002-05-01

    The X-radiation of large-scale extragalactic jets poses a serious challenge for the conventional electron-synchrotron or inverse Compton models suggested to explain the overall non-thermal emission of the resolved knots and hotspots. In this paper I propose an alternative mechanism for X-ray emission - synchrotron radiation by extremely high-energy protons - and discuss implications of this model for the extended jet features resolved by Chandra in several prominent radio galaxies and active galactic nuclei (AGN) - Pictor A, 3C 120, PKS 0637-752 and 3C 273. I show that if protons are indeed accelerated to energies E p >=1018 eV, it is possible to construct a realistic model that allows an effective cooling of protons via synchrotron radiation on quite `comfortable' time-scales of about 107 -108 yr, i.e. on time-scales that provide effective propagation of protons over the jet structures on kpc scales. This explains quite naturally the diffuse character of the observed X-ray emission, as well as the broad range of spectral X-ray indices observed from different objects. Yet, as long as the proton synchrotron cooling time is comparable with both the particle escape time and the age of the jet, the proton-synchrotron model offers an adequate radiation efficiency. The model requires relatively large magnetic field of about 1mG, and proton acceleration rates ranging from L p ~1043 to 1046 ergs-1 . These numbers could be reduced significantly if the jet structures are moving relativistically towards the observer. I discuss also possible contributions of synchrotron radiation by secondary electrons produced at interactions of relatively low energy (E p <=1013 eV) protons with the compressed gas in the jet structures. This is an interesting possibility which however requires a very large product of the ambient gas density and total amount of accelerated protons. Therefore it could be treated as a viable working hypothesis only if one can reduce the intrinsic X

  16. Performance of a novel wafer scale CMOS active pixel sensor for bio-medical imaging

    NASA Astrophysics Data System (ADS)

    Esposito, M.; Anaxagoras, T.; Konstantinidis, A. C.; Zheng, Y.; Speller, R. D.; Evans, P. M.; Allinson, N. M.; Wells, K.

    2014-07-01

    Recently CMOS active pixels sensors (APSs) have become a valuable alternative to amorphous silicon and selenium flat panel imagers (FPIs) in bio-medical imaging applications. CMOS APSs can now be scaled up to the standard 20 cm diameter wafer size by means of a reticle stitching block process. However, despite wafer scale CMOS APS being monolithic, sources of non-uniformity of response and regional variations can persist representing a significant challenge for wafer scale sensor response. Non-uniformity of stitched sensors can arise from a number of factors related to the manufacturing process, including variation of amplification, variation between readout components, wafer defects and process variations across the wafer due to manufacturing processes. This paper reports on an investigation into the spatial non-uniformity and regional variations of a wafer scale stitched CMOS APS. For the first time a per-pixel analysis of the electro-optical performance of a wafer CMOS APS is presented, to address inhomogeneity issues arising from the stitching techniques used to manufacture wafer scale sensors. A complete model of the signal generation in the pixel array has been provided and proved capable of accounting for noise and gain variations across the pixel array. This novel analysis leads to readout noise and conversion gain being evaluated at pixel level, stitching block level and in regions of interest, resulting in a coefficient of variation ⩽1.9%. The uniformity of the image quality performance has been further investigated in a typical x-ray application, i.e. mammography, showing a uniformity in terms of CNR among the highest when compared with mammography detectors commonly used in clinical practice. Finally, in order to compare the detection capability of this novel APS with the technology currently used (i.e. FPIs), theoretical evaluation of the detection quantum efficiency (DQE) at zero-frequency has been performed, resulting in a higher DQE for this

  17. Effect of acceleration on osteoblastic and osteoclastic activities: Analysis of bone metabolism using goldfish scale as a model for bone

    NASA Astrophysics Data System (ADS)

    Suzuki, S.; Kitamura, K.; Nemoto, N.; Shimizu, S.; Wada, W.; Kondo, K.; Tabata, T.; Sodeyama, S.; Ijiri, I.; Hattori, H.

    It is well known that hypo-gravity and hyper-gravity influence bone metabolism However basic data concerning the mechanism are a few because no in vitro model system of human bone is available Human bone consists of osteoblasts osteoclasts and the bone matrix No technique for the co-culture of these components has ever been developed Fish scale is a calcified tissue that contains osteoblasts osteoclasts and bone matrix all of which are similar to those found in human bone Recently we developed a new in vitro model system using goldfish scale This system can simultaneously detect the activities of both scale osteoclasts and osteoblasts with tartrate-resistant acid phosphatase and alkaline phosphatase as the respective markers Using this system we analyzed the bone metabolism under acceleration with a custom-made G-load apparatus Osteoclastic activity in the goldfish scales was suppressed under low-acceleration 0 5-G while osteoblastic activity did not change under this acceleration Under high-acceleration 6-G however the osteoblastic activity of the scales increased In addition the osteoclastic activity of the scales decreased These results suggest that both osteoblastic and osteoclastic activities are regulated by the strength of acceleration Therefore we strongly believe that our in vitro system is useful for analysis of bone metabolism under acceleration

  18. RESTRICTED INTERESTS AND TEACHER PRESENTATION OF ITEMS

    PubMed Central

    Stocco, Corey S; Thompson, Rachel H; Rodriguez, Nicole M

    2011-01-01

    Restricted and repetitive behavior (RRB) is more pervasive, prevalent, frequent, and severe in individuals with autism spectrum disorders (ASDs) than in their typical peers. One subtype of RRB is restricted interests in items or activities, which is evident in the manner in which individuals engage with items (e.g., repetitious wheel spinning), the types of items or activities they select (e.g., preoccupation with a phone book), or the range of items or activities they select (i.e., narrow range of items). We sought to describe the relation between restricted interests and teacher presentation of items. Overall, we observed 5 teachers interacting with 2 pairs of students diagnosed with an ASD. Each pair included 1 student with restricted interests. During these observations, teachers were free to present any items from an array of 4 stimuli selected by experimenters. We recorded student responses to teacher presentation of items and analyzed the data to determine the relation between teacher presentation of items and the consequences for presentation provided by the students. Teacher presentation of items corresponded with differential responses provided by students with ASD, and those with restricted preferences experienced a narrower array of items. PMID:21941381

  19. Restricted interests and teacher presentation of items.

    PubMed

    Stocco, Corey S; Thompson, Rachel H; Rodriguez, Nicole M

    2011-01-01

    Restricted and repetitive behavior (RRB) is more pervasive, prevalent, frequent, and severe in individuals with autism spectrum disorders (ASDs) than in their typical peers. One subtype of RRB is restricted interests in items or activities, which is evident in the manner in which individuals engage with items (e.g., repetitious wheel spinning), the types of items or activities they select (e.g., preoccupation with a phone book), or the range of items or activities they select (i.e., narrow range of items). We sought to describe the relation between restricted interests and teacher presentation of items. Overall, we observed 5 teachers interacting with 2 pairs of students diagnosed with an ASD. Each pair included 1 student with restricted interests. During these observations, teachers were free to present any items from an array of 4 stimuli selected by experimenters. We recorded student responses to teacher presentation of items and analyzed the data to determine the relation between teacher presentation of items and the consequences for presentation provided by the students. Teacher presentation of items corresponded with differential responses provided by students with ASD, and those with restricted preferences experienced a narrower array of items. PMID:21941381

  20. MgcRacGAP restricts active RhoA at the cytokinetic furrow and both RhoA and Rac1 at cell–cell junctions in epithelial cells

    PubMed Central

    Breznau, Elaina B.; Semack, Ansley C.; Higashi, Tomohito; Miller, Ann L.

    2015-01-01

    Localized activation of Rho GTPases is essential for multiple cellular functions, including cytokinesis and formation and maintenance of cell–cell junctions. Although MgcRacGAP (Mgc) is required for spatially confined RhoA-GTP at the equatorial cortex of dividing cells, both the target specificity of Mgc's GAP activity and the involvement of phosphorylation of Mgc at Ser-386 are controversial. In addition, Mgc's function at cell–cell junctions remains unclear. Here, using gastrula-stage Xenopus laevis embryos as a model system, we examine Mgc's role in regulating localized RhoA-GTP and Rac1-GTP in the intact vertebrate epithelium. We show that Mgc's GAP activity spatially restricts accumulation of both RhoA-GTP and Rac1-GTP in epithelial cells—RhoA at the cleavage furrow and RhoA and Rac1 at cell–cell junctions. Phosphorylation at Ser-386 does not switch the specificity of Mgc's GAP activity and is not required for successful cytokinesis. Furthermore, Mgc regulates adherens junction but not tight junction structure, and the ability to regulate adherens junctions is dependent on GAP activity and signaling via the RhoA pathway. Together these results indicate that Mgc's GAP activity down-regulates the active populations of RhoA and Rac1 at localized regions of epithelial cells and is necessary for successful cytokinesis and cell–cell junction structure. PMID:25947135

  1. Antibody-independent activation of the classical pathway of human serum complement by lipid A is restricted to re-chemotype lipopolysaccharide and purified lipid A.

    PubMed Central

    Vukajlovich, S W

    1986-01-01

    Incubation of most bacterial lipopolysaccharides (LPS) with normal human sera at 37 degrees C activates the serum complement system, resulting in decreased levels of hemolytic complement. A panel of R-chemotype LPS preparations isolated from Salmonella minnesota rough mutant strains, as well as smooth wild-type LPS from S. minnesota, Escherichia coli O55-B5, Serratia marcescens, and Yersinia enterolitica, were used to examine the effect of LPS polysaccharide chain length on LPS lipid (lipid A)-dependent activation of the classical pathway of complement (CPC). To examine specific lipid A-dependent activation of the CPC, sera deficient in alternative pathway of complement activity were prepared by the removal of factor D. Absorption of normal human sera with formalinized rabbit erythrocytes was found to remove natural antibodies, factors capable of forming LPS complexes which activate the CPC, or both. By using such factor D-depleted formalinized rabbit erythrocyte-absorbed normal human sera, only isolated lipid A and Re-chemotype LPS (R595 LPS) were found to activate the CPC. Thus, the presence of the additional monosaccharide L-glycero-D-mannoheptose in the Rd2 LPS oligosaccharide chain compared with the L-glycero-D-mannoheptose-deficient Re-chemotype LPS structure is sufficient to block lipid A-dependent activation of the CPC by LPS. PMID:3744547

  2. Effect of nano-scale characteristics of graphene on electrochemical performance of activated carbon supercapacitor electrodes

    NASA Astrophysics Data System (ADS)

    Jasni, M. R. M.; Deraman, M.; Suleman, M.; Hamdan, E.; Sazali, N. E. S.; Nor, N. S. M.; Shamsudin, S. A.

    2016-02-01

    Graphene with its typical nano-scale characteristic properties has been widely used as an additive in activated carbon electrodes in order to enhance the performance of the electrodes for their use in high performance supercapacitors. Activated carbon monoliths (ACMs) electrodes have been prepared by carbonization and activation of green monoliths (GMs) of pre-carbonized fibers of oil palm empty fruit bunches or self-adhesive carbon grains (SACGs) and SACGs added with 6 wt% of KOH-treated multi-layer graphene. ACMs electrodes have been assembled in symmetrical supercapacitor cells that employed aqueous KOH electrolyte (6 M). The cells have been tested with cyclic voltammetry, electrochemical impedance spectroscopy and galvanostatic charge discharge methods to investigate the effect of graphene addition on the specific capacitance (Csp), specific energy (E), specific power (P), equivalent series resistance (ESR) and response time (τo) of the supercapacitor cells. The results show that the addition of graphene in the GMs change the values of Csp, Emax, Pmax, ESR and τo from (61-96) F/g, 2 Wh/kg, 104 W/kg, 2.6 Ω and 38 s, to the respective values of (110-124) F/g, 3 Wh/kg, 156 W/kg, 3.4 Ω and 63 s. This study demonstrates that the graphene addition in the GMs has a significant effect on the electrochemical behavior of the electrodes.

  3. Temporal and spatial variability of soil biological activity at European scale

    NASA Astrophysics Data System (ADS)

    Mallast, Janine; Rühlmann, Jörg

    2015-04-01

    The CATCH-C project aims to identify and improve the farm-compatibility of Soil Management Practices including to promote productivity, climate change mitigation and soil quality. The focus of this work concentrates on turnover conditions for soil organic matter (SOM). SOM is fundamental for the maintenance of quality and functions of soils while SOM storage is attributed a great importance in terms of climate change mitigation. The turnover conditions depend on soil biological activity characterized by climate and soil properties. Soil biological activity was investigated using two model concepts: a) Re_clim parameter within the ICBM (Introductory Carbon Balance Model) (Andrén & Kätterer 1997) states a climatic factor summarizing soil water storage and soil temperature and its influence on soil biological activity. b) BAT (biological active time) approach derived from model CANDY (CArbon and Nitrogen Dynamic) (Franko & Oelschlägel 1995) expresses the variation of soil moisture, soil temperature and soil aeration as a time scale and an indicator of biological activity for soil organic matter (SOM) turnover. During an earlier stage both model concepts, Re_clim and BAT, were applied based on a monthly data to assess spatial variability of turnover conditions across Europe. This hampers the investigation of temporal variability (e.g. intra-annual). The improved stage integrates daily data of more than 350 weather stations across Europe presented by Klein Tank et al. (2002). All time series data (temperature, precipitation and potential evapotranspiration and soil texture derived from the European Soil Database (JRC 2006)), are used to calculate soil biological activity in the arable layer. The resulting BAT and Re_clim values were spatio-temporal investigated. While "temporal" refers to a long-term trend analysis, "spatial" includes the investigation of soil biological activity variability per environmental zone (ENZ, Metzger et al. 2005 representing similar

  4. Development and validation of a scale to measure Latino parenting strategies related to children's obesigenic behaviors. The parenting strategies for eating and activity scale (PEAS).

    PubMed

    Larios, Sandra E; Ayala, Guadalupe X; Arredondo, Elva M; Baquero, Barbara; Elder, John P

    2009-02-01

    Research has shown that children's dietary and activity-related behaviors are shaped by the family environment and parenting behaviors. The present study describes the development and validation of a bilingual (Spanish and English) scale assessing parenting strategies associated with children's dietary and activity-related behaviors in the home. Items were generated from focus groups with Latina mothers and a review of the literature, and two different samples were used to assess the scale's psychometric properties, including an examination of predictive validity using measured child body mass index. Factor analysis of the first sample (N=91) yielded a 5-factor solution (limit setting, monitoring, discipline, control and concern) and accounted for 65% of the variance. Confirmatory factor analyses on a second sample of Latina mothers recruited into a childhood obesity prevention study (N=714) showed that a 26-item 5-factor solution (limit setting, monitoring, discipline, control and reinforcement) provided the best fit for the data. Parenting strategies characterized as controlling were associated with a lower BMI among children. After using multiple samples and establishing its validity, the parenting strategies for eating and activity scale (PEAS) was found to be valid and reliable in measuring Latino parenting strategies related to children's dietary and activity-related behaviors. PMID:18845197

  5. Range Restriction and Attenuation Corrections.

    ERIC Educational Resources Information Center

    Mumford, Michael D.; Mendoza, Jorge L.

    The present paper reviews the techniques commonly used to correct an observed correlation coefficient for the simultaneous influence of attenuation and range restriction effects. It is noted that the procedure which is currently in use may be somewhat biased because it treats range restriction and attenuation as independent restrictive influences.…

  6. Development and Validation of the Comprehensive Health Activities Scale: A New Approach to Health Literacy Measurement

    PubMed Central

    CURTIS, LAURA M.; REVELLE, WILLIAM; AND, KATHERINE WAITE; WILSON, ELIZABETH A. H.; CONDON, DAVID M.; BOJARSKI, ELIZABETH; PARK, DENISE C.; AND, DAVID W. BAKER; WOLF, MICHAEL S.

    2014-01-01

    Current health literacy measures have been criticized for solely measuring reading and numeracy skills when a broader set of skills is necessary for making informed health decisions, especially when information is often conveyed verbally and through multimedia video. We devised nine health tasks and a corresponding 190 item assessment to more comprehensively measure health literacy skills. A sample of 826 participants age 55-74 recruited from an academic General Internal Medicine practice and three Federally Qualified Health Centers in Chicago, Illinois completed the assessment. Items were reduced using hierarchical factor analysis and item response theory resulting in the 45-item Comprehensive Health Activities Scale (CHAS). All 45 items loaded on one general latent trait and the resulting scale demonstrated high reliability and strong construct validity using measures of health literacy and global cognitive functioning. The predictive validity of the CHAS using self-reported general, physical, and mental health status was comparable to or better than widely used measures of health literacy, depending on the outcome. Despite comprehensively measuring health literacy skills, items in the CHAS supported one primary construct. With similar psychometric properties, current measures may be adequate, depending on the purpose of the assessment. PMID:25375025

  7. Lab-scale experimental strategy for determining micropollutant partition coefficient and biodegradation constants in activated sludge.

    PubMed

    Pomiès, M; Choubert, J M; Wisniewski, C; Miège, C; Budzinski, H; Coquery, M

    2015-03-01

    The nitrifying/denitrifying activated sludge process removes several micropollutants from wastewater by sorption onto sludge and/or biodegradation. The objective of this paper is to propose and evaluate a lab-scale experimental strategy for the determination of partition coefficient and biodegradation constant for micropollutant with an objective of modelling their removal. Four pharmaceutical compounds (ibuprofen, atenolol, diclofenac and fluoxetine) covering a wide hydrophobicity range (log Kow from 0.16 to 4.51) were chosen. Dissolved and particulate concentrations were monitored for 4 days, inside two reactors working under aerobic and anoxic conditions, and under different substrate feed conditions (biodegradable carbon and nitrogen). We determined the mechanisms responsible for the removal of the target compounds: (i) ibuprofen was biodegraded, mainly under aerobic conditions by cometabolism with biodegradable carbon, whereas anoxic conditions suppressed biodegradation; (ii) atenolol was biodegraded under both aerobic and anoxic conditions (with a higher biodegradation rate under aerobic conditions), and cometabolism with biodegradable carbon was the main mechanism; (iii) diclofenac and fluoxetine were removed by sorption only. Finally, the abilities of our strategy were evaluated by testing the suitability of the parameters for simulating effluent concentrations and removal efficiency at a full-scale plant. PMID:25300180

  8. Pilot-scale study of powdered activated carbon recirculation for micropollutant removal.

    PubMed

    Meinel, F; Sperlich, A; Jekel, M

    2016-01-01

    Adsorption onto powdered activated carbon (PAC) is a promising technique for the removal of organic micropollutants (OMPs) from treated wastewater. To enhance the adsorption efficiency, PAC is recycled back into the adsorption stage. This technique was examined in pilot scale in comparison to a reference without recirculation. Coagulation with Fe(3+) was carried out simultaneously to adsorption. Extensive OMP measurements showed that recirculation significantly increased OMP eliminations. Thus, significant PAC savings were feasible. The PAC concentration in the contact reactor proved to be an important operating parameter that can be surrogated by the easily measurable total suspended solids (TSS) concentration. OMP eliminations increased with increasing TSS concentrations. At 20 mg PAC L(-1) and 2.8 g TSS L(-1) in the contact reactor, well-adsorbable carbamazepine was eliminated by 97%, moderately adsorbable diclofenac was eliminated by 92% and poorly-adsorbable acesulfame was eliminated by 54% in comparison to 49%, 35% and 18%, respectively, without recirculation. The recirculation system represents an efficient technique, as the PAC's adsorption capacity is practically completely used. Small PAC dosages yield high OMP eliminations. Poorly-adsorbable gabapentin was eliminated to an unexpectedly high degree. A laboratory-scale biomass inhibition study showed that aerobic biodegradation removed gabapentin in addition to adsorption. PMID:27533867

  9. Formation of δ-Sunspot in Simulations of Active-Region-Scale Flux Emergence

    NASA Astrophysics Data System (ADS)

    Fang, Fang; Fan, Yuhong

    2015-04-01

    δ-sunspots, with highly complex magnetic structures, are very productive in energetic eruptive events, such as X-class flares and homologous eruptions. We here study the formation of such complex magnetic structures by numerical simulations of magnetic flux emergence from the convection zone into the corona in an active-region-scale domain. In our simulation, two pairs of bipolar sunspots form on the surface, originating from two buoyant segments of a single subsurface twisted flux rope. Expansion and rotation of the emerging fields in the two bipoles drive the two opposite polarities into each other with apparent rotating motion, producing a compact δ-sunspot with a sharp polarity inversion line. The formation of the δ-sunspot in such a realistic-scale domain produces emerging pattherns similar to those formed in observations, e.g. the inverted polarity against Hale’s law, the curvilinear motion of the spot, strong transverse field with highly sheared magnetic and velocity fields at the PIL. Strong current builds up at the PIL, giving rise to reconnection, which produces a complex coronal magnetic connectivity with non-potential fields in the -spot overlaid by more relaxed fields connecting the two polarities at the two ends.

  10. δ-Sunspot Formation in Simulation of Active-region-scale Flux Emergence

    NASA Astrophysics Data System (ADS)

    Fang, Fang; Fan, Yuhong

    2015-06-01

    δ-sunspots, with highly complex magnetic structures, are very productive in energetic eruptive events, such as X-class flares and homologous eruptions. We here study the formation of such complex magnetic structures by numerical simulations of magnetic flux emergence from the convection zone into the corona in an active-region-scale domain. In our simulation, two pairs of bipolar sunspots form on the surface, originating from two buoyant segments of a single subsurface twisted flux rope, following the approach of Toriumi et al. Expansion and rotation of the emerging fields in the two bipoles drive the two opposite polarities into each other with apparent rotating motion, producing a compact δ-sunspot with a sharp polarity inversion line. The formation of the δ-sunspot in such a realistic-scale domain produces emerging patterns similar to those formed in observations, e.g., the inverted polarity against Hale's law, the curvilinear motion of the spot, and strong transverse field with highly sheared magnetic and velocity fields at the polarity inversion line (PIL). Strong current builds up at the PIL, giving rise to reconnection, which produces a complex coronal magnetic connectivity with non-potential fields in the δ-spot overlaid by more relaxed fields connecting the two polarities at the two ends.

  11. Scaling law for the ion-induced electronic sputtering of intact biomolecules: Evidence of thermal activation

    SciTech Connect

    Szenes, G.

    2004-09-01

    A linear scaling is found for intact biomolecules in the form of ln(Y/S{sub e})-1/S{sub e} where Y, and S{sub e} are the sputtering yield and the electronic stopping power, respectively. The law is in good agreement with the experimental data for valine, leucine, and insulin molecules in various charge states in a broad range of S{sub e}. The thermal spike model of the author is applied and the activation energies of desorption U are obtained from the slope of the semilogarithmic lines. U is considerably higher for neutral leucine molecules than for ions. The Coulomb contribution to U for molecular ions does not depend on S{sub e} in a broad range. During sputtering, the specific heat is approximately 10% of its room temperature value for valine and leucine.

  12. Assessment of impairment in activities of daily living in mild cognitive impairment using an individualized scale.

    PubMed

    Chaves, Giseli de Fátima Dos Santos; Oliveira, Alexandra Martini; Chaves, Juliana Aparecida Dos Santos; Forlenza, Orestes Vicente; Aprahamian, Ivan; Nunes, Paula Villela

    2016-07-01

    Mild impairment in activities of daily living (ADL) can occur in Mild Cognitive Impairment (MCI), but the nature and extent of these difficulties need to be further explored. The Canadian occupational performance measure (COPM) is one of the few individualized scales designed to identify self-perceived difficulties in ADL. The present study investigated impairments in ADL using the COPM in elderly with MCI. A total of 58 MCI patients were submitted to the COPM for studies of its validity and reliability. The COPM proved a valid and consistent instrument for evaluating ADL in elderly MCI patients. A total of 74.6% of the MCI patients reported difficulties in ADL. Of these problems, 41.2% involved self-care, 31.4% productivity and 27.4% leisure. This data further corroborates recent reports of possible functional impairment in complex ADL in MCI. PMID:27487375

  13. Design of plasmonic photodetector with high absorptance and nano-scale active regions.

    PubMed

    Guo, Jingshu; Wu, Zhiwei; Li, Yuan; Zhao, Yanli

    2016-08-01

    We propose a novel plasmonic photodetector with high responsivity, utilizing nano-scale active regions. This design can be applied to diverse materials (group III-V or IV materials) and different operation wavelengths covering the O-U bands. The periodic structure utilizing Surface Plasmon Polariton Bloch Waves (SPP-BWs) has low optical power loss. FDTD simulation shows an absorptance of 74.4% which means a responsivity of about 0.74 A/W at 1550 nm. The low capacitance brings low noise, reduced power consumption, and a high electrical bandwidth which is estimated to be 140 GHz. Among the plasmonic PDs with inherent high speeds but low responsivities, our design makes the obvious progress on improving the absorptance. PMID:27505787

  14. The largest mid-infrared atlas of active galactic nuclei at sub-arcsecond spatial scales

    NASA Astrophysics Data System (ADS)

    Asmus, Daniel; Gandhi, Poshak; Honig, Sebastian F.; Smette, Alain

    2012-12-01

    We present the largest mid-infrared atlas of active galactic nuclei at sub-arcsecond spatial scales containing 249 objects. It comprises all ground-based HR MIR observations performed to date. This catalog includes a large number of new observations. The photometry in multiple filters allows for characterizing the properties of the dust emission for most objects. Because of its size and characteristics, this sample is very well-suited for AGN unification studies. In particular, we discuss the enlarged MIR-X-ray correlation which extends over six orders of magnitude in luminosity and potentially probes different physical mechanisms. Finally, tests for intrinsic differences between the AGN types are presented and we discuss dependencies of MIR-X-ray properties with respect to fundamental AGN parameters such as accretion rate and the column density and covering factor of obscuring material.

  15. The Growth Factor Receptor ERBB2 Regulates Mitochondrial Activity on a Signaling Time Scale*

    PubMed Central

    Patel, Nirav; Barrientos, Antoni; Landgraf, Ralf

    2013-01-01

    Overexpression of the ERBB2 receptor tyrosine kinase and the mitochondrial inner membrane protein UCP2 occurs frequently in aggressive cancers with dysfunctional mitochondria. Overexpressed ERBB2 signals constitutively and elevated UCP2 can uncouple mitochondria and alleviate oxidative stress. However, the physiological contributions of UCP2 and ERBB2 at the low expression levels that are typical of most tissues, as well as the path to oncogenic deregulation, are poorly understood. We now show that ERBB2 directly controls UCP2 levels, both at low physiological levels and oncogenic overexpression. At low levels of receptor and UCP2, ligand stimulation creates a distinct temporal response pattern driven by the opposing forces of translational suppression of the exceptionally short lived UCP2 protein and a time delayed transcriptional up-regulation. The latter becomes dominant through constitutive signaling by overexpressed ERBB2, resulting in high levels of UCP2 that contribute mitochondrial uncoupling. By contrast, ligand stimulation of non-overexpressed ERBB2 transiently removes UCP2 and paradoxically reduces the mitochondrial membrane potential, oxygen consumption, and OXPHOS on a signaling time scale. However, neither the transporter activity nor down-regulation of already low UCP2 levels drive this reduction in mitochondrial activity. Instead, UCP2 is required to establish mitochondria that are capable of responding to ligand. UCP2 knockdown impairs proliferation at high glucose but its absence specifically impairs ligand-induced growth when glucose levels fluctuate. These findings demonstrate the ability of growth factor signaling to control oxidative phosphorylation on a signaling time scale and point toward a non-transporter role for low levels of UCP2 in establishing dynamic response capability. PMID:24142693

  16. [A behavioural rating scale of activity engagement in psychogeriatric day care].

    PubMed

    Diesfeldt, H F A

    2014-09-01

    The Participation Scale was developed as an observational measure of activity engagement (as rated by group facilitators) of adult day care clients with mild to moderate dementia. In a consecutive sample of 448 subjects Mokken scaling procedure was conducted to assess the latent structure of 27 questionnaire items. The study included an exploratory and a confirmatory approach. For that purpose the sample was randomly divided into two halves. Exploratory analysis revealed three dimensions of participation that adequately captured the item structure: motivation (10 items; Loevinger's H = 0.48), competence (7 items; H = 0.56) and self-confidence (4 items; H = 0.57). The structure was validated in a confirmatory analysis. In a stepwise multiple regression model 49% of the variance in motivation was explained by independent behavioural measures of apathy and affect. Apathy and cognitive impairment were significant predictors of competence in participation (R(2) = 31.2%). Negative affect was the main predictor of reduced self-confidence (R(2) = 37.9%). Cross-validation of these exploratory regression models on the confirmatory sample explained 39.6%, 29.2% and 23.1% of the variance in motivation, competence and self-confidence, respectively. Test-retest intraclass correlation coefficients (ICC2(A,1)) as determined in a random subsample of 56 participants, were 0.77 (motivation), 0.85 (competence) and 0.76 (self-confidence). The three measures allow the differentiation and ordering of individual participants on separate dimensions of activity engagement in psychogeriatric day care. PMID:25007866

  17. The Student-Centered Active Learning Environment for Undergraduate Programs (SCALE-UP) Project

    NASA Astrophysics Data System (ADS)

    Beichner, Robert J.

    2011-04-01

    How do you keep a classroom of 100 undergraduates actively learning? Can students practice communication and teamwork skills in a large class? How do you boost the performance of underrepresented groups? The Student-Centered Active Learning Environment for Undergraduate Programs (SCALE-UP) Project has addressed these concerns. Because of their inclusion in a leading introductory physics textbook, project materials are used by more than 1/3 of all science, math, and engineering majors nationwide. The room design and pedagogy have been adopted at more than 100 leading institutions across the country. Physics, chemistry, math, astronomy, biology, engineering, earth sciences, and even literature classes are currently being taught this way. Educational research indicates that students should collaborate on interesting tasks and be deeply involved with the material they are studying. We promote active learning in a redesigned classroom for 100 students or more. (Of course, smaller classes can also benefit.) Class time is spent primarily on "tangibles" and "ponderables"--hands-on activities, simulations, and interesting questions. Nine students sit in three teams at round tables. Instructors circulate and engage in Socratic dialogues. The setting looks like a banquet hall, with lively interactions nearly all the time. Hundreds of hours of classroom video and audio recordings, transcripts of numerous interviews and focus groups, data from conceptual learning assessments (using widely-recognized instruments in a pretest/posttest protocol), and collected portfolios of student work are part of our rigorous assessment effort. Our findings (based on data from over 16,000 students collected over five years as well as replications at adopting sites) can be summarized as the following: 1) Female failure rate is 1/5 of previous levels, even though more is demanded of students. 2) Minority failure rate is 1/4 that seen in traditionally taught courses. 3) At-risk students are more

  18. Removal of micropollutants and reduction of biological activity in a full scale reclamation plant using ozonation and activated carbon filtration.

    PubMed

    Reungoat, J; Macova, M; Escher, B I; Carswell, S; Mueller, J F; Keller, J

    2010-01-01

    Pharmaceutical compounds are found in secondary treated effluents up to microg L(-1) levels and therefore discharged into surface waters. Since the long term effects of these compounds on the environment and human health are, to date, largely unknown, implementation of advanced treatment of wastewaters is envisaged to reduce their discharge. This is of particular relevance where surface waters are used as drinking water sources and when considering indirect potable reuse. This study aimed at assessing the removal of organic micropollutants and the concurrent reduction of their biological activity in a full scale reclamation plant treating secondary effluent. The treatment consists of 6 stages: denitrification, pre-ozonation, coagulation/flocculation/dissolved air flotation and filtration (DAFF), main ozonation, activated carbon filtration and final ozonation for disinfection. For that purpose, representative 24-hour composite samples were collected after each stage. The occurrence of 85 compounds was monitored by LC/MS-MS. A battery of 6 bioassays was also used as a complementary tool to evaluate non-specific toxicity and 5 specific toxic modes of action. Results show that, among the 54 micropollutants quantified in the influent water, 50 were removed to below their limit of quantification representing more than 90% of concentration reduction. Biological activity was reduced, depending on the specific response that was assessed, from a minimum of 62% (AhR response) to more than 99% (estrogenicity). The key processes responsible for the plant's performances were the coagulation/flocculation/DAFF, main ozonation and activated carbon filtration. The effect of these 3 processes varied from one compound or bioassay to another but their combination was almost totally responsible for the overall observed reduction. Bioassays yielded complementary information, e.g. estrogenic compounds were not detected in the secondary effluent by chemical analysis, but the samples had an

  19. Determination of paleoseismic activity over a large time-scale: Fault scarp dating with 36Cl

    NASA Astrophysics Data System (ADS)

    Mozafari Amiri, Nasim; Tikhomirov, Dmitry; Sümer, Ökmen; Özkaymak, Çaǧlar; Uzel, Bora; Ivy-Ochs, Susan; Vockenhuber, Christof; Sözbilir, Hasan; Akçar, Naki

    2016-04-01

    Bedrock fault scarps are the most direct evidence of past earthquakes to reconstruct seismic activity in a large time-scale using cosmogenic 36Cl dating if built in carbonates. For this method, a surface along the fault scarp with a minimum amount of erosion is required to be chosen as an ideal target point. The section of the fault selected for sampling should cover at least two meters of the fault surface from the lower part of the scarp, where intersects with colluvium wedge. Ideally, sampling should be performed on a continuous strip along the direction of the fault slip direction. First, samples of 10 cm high and 15 cm wide are marked on the fault surface. Then, they are collected using cutters, hammer and chisel in a thickness of 3 cm. The main geometrical factors of scarp dip, scarp height, top surface dip and colluvium dip are also measured. Topographic shielding in the sampling spot is important to be estimated as well. Moreover, density of the fault scarp and colluvium are calculated. The physical and chemical preparations are carried in laboratory for AMS and chemical analysis of the samples. A Matlab® code is used for modelling of seismically active periods based on increasing production rate of 36Cl following each rupture, when a buried section of a fault is exposed. Therefore, by measuring the amount of cosmogenic 36Cl versus height, the timing of major ruptures and their offsets are determined. In our study, Manastır, Mugırtepe and Rahmiye faults in Gediz graben, Priene-Sazlı, Kalafat and Yavansu faults in Büyük Menderes graben and Ören fault in Gökava half-graben have been examined in the seismically active region of Western Turkey. Our results reconstruct at least five periods of high seismic activity during the Holocene time, three of which reveal seismic ruptures beyond the historical pre-existing data.

  20. From baseline to epileptiform activity: A path to synchronized rhythmicity in large-scale neural networks

    NASA Astrophysics Data System (ADS)

    Shusterman, Vladimir; Troy, William C.

    2008-06-01

    In large-scale neural networks in the brain the emergence of global behavioral patterns, manifested by electroencephalographic activity, is driven by the self-organization of local neuronal groups into synchronously functioning ensembles. However, the laws governing such macrobehavior and its disturbances, in particular epileptic seizures, are poorly understood. Here we use a mean-field population network model to describe a state of baseline physiological activity and the transition from the baseline state to rhythmic epileptiform activity. We describe principles which explain how this rhythmic activity arises in the form of spatially uniform self-sustained synchronous oscillations. In addition, we show how the rate of migration of the leading edge of the synchronous oscillations can be theoretically predicted, and compare the accuracy of this prediction with that measured experimentally using multichannel electrocorticographic recordings obtained from a human subject experiencing epileptic seizures. The comparison shows that the experimentally measured rate of migration of the leading edge of synchronous oscillations is within the theoretically predicted range of values. Computer simulations have been performed to investigate the interactions between different regions of the brain and to show how organization in one spatial region can promote or inhibit organization in another. Our theoretical predictions are also consistent with the results of functional magnetic resonance imaging (fMRI), in particular with observations that lower-frequency electroencephalographic (EEG) rhythms entrain larger areas of the brain than higher-frequency rhythms. These findings advance the understanding of functional behavior of interconnected populations and might have implications for the analysis of diverse classes of networks.

  1. Ozonation effects for excess sludge reduction on bacterial communities composition in a full-scale activated sludge plant for domestic wastewater treatment.

    PubMed

    Chiellini, C; Gori, R; Tiezzi, A; Brusetti, L; Pucciarelli, S; D'Amato, E; Chiavola, A; Sirini, P; Lubello, C; Petroni, G

    2014-01-01

    Activated sludge process is the most widely diffused system to treat wastewater to control the discharge of pollutants into the environment. Microorganisms are responsible for the removal of organic matter, nitrogen, phosphorous and other emerging contaminants. The environmental conditions of biological reactors significantly affects the ecology of the microbial community and, therefore, the performance of the treatment process. In the last years, ozone has been used to reduce excess sludge production by wastewater treatment plants (WWTPs), whose disposal represents one of the most relevant operational costs. The ozonation process has demonstrated to be a viable method to allow a consistent reduction in excess sludge. This study was carried out in a full-scale plant treating municipal wastewater in two parallel lines, one ozonated in the digestion tank and another used as a control. Bacterial communities of samples collected from both lines of digestion thanks were then compared to assess differences related to the ozonation treatment. Data were then analysed with terminal restriction fragment length polymorphism (T-RFLP) analysis on 16S rRNA gene. Differences between bacterial communities of both treated and untreated line appeared 2 weeks after the beginning of the treatment. Results demonstrated that ozonation treatment significantly affected the activated sludge in WWTP. PMID:24701944

  2. Network effect of knowledge spillover: Scale-free networks stimulate R&D activities and accelerate economic growth

    NASA Astrophysics Data System (ADS)

    Konno, Tomohiko

    2016-09-01

    We study how knowledge spillover networks affect research and development (R&D) activities and economic growth. For this purpose, we extend a Schumpeterian growth model to the one on networks that depict the knowledge spillover relationships of R&D. We show that scale-free networks stimulate R&D activities and accelerate economic growth.

  3. Cohort Profile of the Goals Study: A Large-Scale Research of Physical Activity in Dutch Students

    ERIC Educational Resources Information Center

    de Groot, Renate H. M.; van Dijk, Martin L.; Kirschner, Paul A.

    2015-01-01

    The GOALS study (Grootschalig Onderzoek naar Activiteiten van Limburgse Scholieren [Large-scale Research of Activities in Dutch Students]) was set up to investigate possible associations between different forms of physical activity and inactivity with cognitive performance, academic achievement and mental well-being. It was conducted at a…

  4. A Step Towards Seascape Scale Conservation: Using Vessel Monitoring Systems (VMS) to Map Fishing Activity

    PubMed Central

    Witt, Matthew J.; Godley, Brendan J.

    2007-01-01

    Background Conservation of marine ecosystems will require a holistic understanding of fisheries with concurrent spatial patterns of biodiversity. Methodology/Principal Findings Using data from the UK Government Vessel Monitoring System (VMS) deployed on UK-registered large fishing vessels we investigate patterns of fisheries activity on annual and seasonal scales. Analysis of VMS data shows that regions of the UK European continental shelf (i.e. Western Channel and Celtic Sea, Northern North Sea and the Goban Spur) receive consistently greater fisheries pressure than the rest of the UK continental shelf fishing zone. Conclusions/Significance VMS provides a unique and independent method from which to derive patterns of spatially and temporally explicit fisheries activity. Such information may feed into ecosystem management plans seeking to achieve sustainable fisheries while minimising putative risk to non-target species (e.g. cetaceans, seabirds and elasmobranchs) and habitats of conservation concern. With multilateral collaboration VMS technologies may offer an important solution to quantifying and managing ecosystem disturbance, particularly on the high-seas. PMID:17971874

  5. Vertebrate Protein CTCF and its Multiple Roles in a Large-Scale Regulation of Genome Activity

    PubMed Central

    Nikolaev, L.G; Akopov, S.B; Didych, D.A; Sverdlov, E.D

    2009-01-01

    The CTCF transcription factor is an 11 zinc fingers multifunctional protein that uses different zinc finger combinations to recognize and bind different sites within DNA. CTCF is thought to participate in various gene regulatory networks including transcription activation and repression, formation of independently functioning chromatin domains and regulation of imprinting. Sequencing of human and other genomes opened up a possibility to ascertain the genomic distribution of CTCF binding sites and to identify CTCF-dependent cis-regulatory elements, including insulators. In the review, we summarized recent data on genomic distribution of CTCF binding sites in the human and other genomes within a framework of the loop domain hypothesis of large-scale regulation of the genome activity. We also tried to formulate possible lines of studies on a variety of CTCF functions which probably depend on its ability to specifically bind DNA, interact with other proteins and form di- and multimers. These three fundamental properties allow CTCF to serve as a transcription factor, an insulator and a constitutive dispersed genome-wide demarcation tool able to recruit various factors that emerge in response to diverse external and internal signals, and thus to exert its signal-specific function(s). PMID:20119526

  6. Vertebrate Protein CTCF and its Multiple Roles in a Large-Scale Regulation of Genome Activity.

    PubMed

    Nikolaev, L G; Akopov, S B; Didych, D A; Sverdlov, E D

    2009-08-01

    The CTCF transcription factor is an 11 zinc fingers multifunctional protein that uses different zinc finger combinations to recognize and bind different sites within DNA. CTCF is thought to participate in various gene regulatory networks including transcription activation and repression, formation of independently functioning chromatin domains and regulation of imprinting. Sequencing of human and other genomes opened up a possibility to ascertain the genomic distribution of CTCF binding sites and to identify CTCF-dependent cis-regulatory elements, including insulators. In the review, we summarized recent data on genomic distribution of CTCF binding sites in the human and other genomes within a framework of the loop domain hypothesis of large-scale regulation of the genome activity. We also tried to formulate possible lines of studies on a variety of CTCF functions which probably depend on its ability to specifically bind DNA, interact with other proteins and form di- and multimers. These three fundamental properties allow CTCF to serve as a transcription factor, an insulator and a constitutive dispersed genome-wide demarcation tool able to recruit various factors that emerge in response to diverse external and internal signals, and thus to exert its signal-specific function(s). PMID:20119526

  7. Dielectric elastomer based active layer for macro-scaled industrial application in roto-flexographic printing

    NASA Astrophysics Data System (ADS)

    Pinto, F.; D'Oriano, G.; Meo, M.

    2014-03-01

    The use of dielectric elastomer (DE) for the realisation of new generation actuators has attracted the interest of many researchers in the last ten years due to their high efficiency, a very good electromechanical coupling and large achievable strains [1-3]. Although these properties constitute a very important advantage, the industrial exploitation of such systems is hindered by the high voltages required for the actuation [4] that could potentially constitute also a risk for the operators. In this work we present a DE based active layer that can be used in different macro-scaled parts of industrial equipment for roto-flexographic printing substituting traditional mechanical devices, reducing manufacturing costs and enhancing its reliability. Moreover, the specific configuration of the system requires the driving voltage to be applied only in the mounting/dismounting step thus lowering further the operative costs without posing any threat for the workers. Starting from the industrial requirements, a complete thermo-mechanical characterisation using DSC and DMA was undertaken on acrylic elastomer films in order to investigate their behaviour under the operative frequencies and solicitations. Validation of the active layer was experimentally evaluated by manufacturing a DE actuator controlling both prestrain and nature of the complaint electrodes, and measuring the electrically induced Maxwell's strain using a laser vibrometer to evaluate the relative displacement along the z-axis.

  8. Comparison of dielectric materials for the activation of a macro-scale hinge configuration

    NASA Astrophysics Data System (ADS)

    Jordi, C.; Schmidt, A.; Kovacs, G.; Ermanni, Paolo

    2011-04-01

    While much of the research on dielectric elastomer actuators used to concentrate on VHB 4910 as dielectric material, lately many new, specifically developed materials have come into focus. The acrylic VHB has been thoroughly characterized in a macro-scale agonist-antagonist configuration on an active hinge. This was carried out with the aim of using it on an airship, which was activated, undulating body and a fin and thus propelled in a fish-like manner. The concept was proved in flight, but still lifetime and viscosity of the actuators and the time-costing fabrication due to the necessary large pre-stretches of the dielectric membrane caused severe inconveniences. In order to evaluate the usability of other materials for this specific purpose, two other materials, a corrugated silicone with silver electrodes (by PolyPower) and an acrylic with interpenetrating network (IPN) developed by Pei et al. were characterized under similar conditions. The influence of the material on performance and design of the actuators and the conclusions for the use of the materials on the airship (and on applications with similar performance requirements) are presented.

  9. Infrared-active quadruple contrast FePt nanoparticles for multiple scale molecular imaging.

    PubMed

    Chou, Shang-Wei; Liu, Chien-Liang; Liu, Tzu-Ming; Shen, Yu-Fang; Kuo, Lun-Chang; Wu, Cheng-Ham; Hsieh, Tsung-Yuan; Wu, Pei-Chun; Tsai, Ming-Rung; Yang, Che-Chang; Chang, Kai-Yao; Lu, Meng-Hua; Li, Pai-Chi; Chen, Shi-Ping; Wang, Yu-Hsin; Lu, Chen-Wen; Chen, Yi-An; Huang, Chih-Chia; Wang, Churng-Ren Chris; Hsiao, Jong-Kai; Li, Meng-Lin; Chou, Pi-Tai

    2016-04-01

    A single nanomaterial with multiple imaging contrasts and functions is highly desired for multiscale theragnosis. Herein, we demonstrate single 1-1.9 μm infrared-active FePt alloy nanoparticles (FePt NPs) offering unprecedented four-contrast-in-one molecular imaging - computed tomography (CT), magnetic resonance imaging (MRI), photoacoustic (PA) imaging, and high-order multiphoton luminescence (HOMPL) microscopy. The PA response of FePt NPs outperforms that of infrared-active gold nanorods by 3- to 5.6-fold under identical excitation fluence and particle concentrations. HOMPL (680 nm) of an isolated FePt NP renders spatial full-width-at-half-maximum values of 432 nm and 300 nm beyond the optical diffraction limit for 1230-nm and 920-nm excitation, respectively. The in vivo targeting function was successfully visualized using HOMPL, PA imaging, CT, and MRI, thereby validating FePt as a single nanomaterial system covering up to four types (Optical/PA/CT/MRI) of molecular imaging contrast, ranging from the microscopic level to whole-body scale investigation. PMID:26854391

  10. Active and Social Data Curation: Reinventing the Business of Community-scale Lifecycle Data Management

    NASA Astrophysics Data System (ADS)

    McDonald, R. H.; Kumar, P.; Plale, B. A.; Myers, J.; Hedstrom, M. L.

    2012-12-01

    Effective long-term curation and preservation of data for community use has historically been limited to high-value and homogeneous collections produced by mission-oriented organizations. The technologies and practices that have been applied in these cases, e.g. relational data bases, development of comprehensive standardized vocabularies, and centralized support for reference data collections, are arguably applicable to the much broader range of data generated by the long tail of investigator-led research, with the logical conclusion of such an argument leading to the call for training, evangelism, and vastly increased funding as the best means of broadening community-scale data management. In this paper, we question this reasoning and explore how alternative approaches focused on the overall data lifecycle and the sociological and business realities of distributed multi-disciplinary research communities might dramatically lower costs, increase value, and consequently drive dramatic advances in our ability to use and re-use data, and ultimately enable more rapid scientific advance. Specifically, we introduce the concepts of active and social curation as a means to decrease coordination costs, align costs and values for individual data producers and data consumers, and improve the immediacy of returns for data curation investments. Further, we describe the specific architecture and services for active and social curation that are being prototyped within the Sustainable Environment - Actionable Data (SEAD) project within NSF's DataNet network and discuss how they are motivated by the long-tail dynamics in the cross-disciplinary sustainability research community.

  11. Activation of CD1d-restricted natural killer T cells can inhibit cancer cell proliferation during chemotherapy by promoting the immune responses in murine mesothelioma.

    PubMed

    Wu, Licun; Yun, Zhihong; Tagawa, Tetsuzo; De la Maza, Luis; Wu, Matthew Onn; Yu, Julie; Zhao, Yidan; de Perrot, Marc

    2014-12-01

    We studied the impact of natural killer T (NKT) cell activation by alpha-galactocysylceramide (α-GalCer, α-GC) on cancer cell repopulation during chemotherapy in murine mesothelioma. The number of NKT cells was found to be increased during the development of murine mesothelioma. NKT cells specifically recognize α-GC through CD1d resulting in their activation and expansion. Tumor-bearing mice were treated with chemotherapy once weekly, and α-GC was followed after each cycle of chemotherapy. Anti-tumor effect was evaluated on wild-type (WT) and CD1d knockout (CD1dKO) mice. Cancer cell proliferation and apoptosis were evaluated by Ki67 and TUNEL immunohistochemistry. CD4(+) and CD8(+) T cell proportion and activation in tumor, spleen, draining lymph node and peripheral blood were determined by flow cytometry, and gene expression of activated T cell-related cytokines was quantified by reverse transcription PCR. NKT cells were identified by CD1d-α-GC-tetramer staining. In WT mice, tumor growth delay was achieved by cisplatin (Cis), and this effect was improved in combination with α-GC, but α-GC alone had little effect. Cancer cell proliferation during chemotherapy was significantly inhibited by α-GC, while cancer cell death was significantly upregulated. α-GC following chemotherapy resulted in NKT cell expansion and an increase of interferon-γ production in the draining lymph node, blood and spleen. Gene expression of immune-associated cytokines was upregulated. Strikingly, the percentage of inducible T cell co-stimulator(+)CD4 T cells, Th17/Tc17 cells increased in splenocytes. In CD1d KO mice, however, Cis alone was less effective and Cis + α-GC provided no additional benefit over Cis alone. α-GC alone had minimal effect in both mice. NKT activation between cycles of chemotherapy could improve the outcome of mesothelioma treatment. PMID:25183171

  12. Video monitoring of meso-scale aeolian activity on a narrow beach

    NASA Astrophysics Data System (ADS)

    Hage, Pam; Ruessink, Gerben

    2014-05-01

    The morphologic evolution of coastal dunes is inextricably linked to the neighbouring beach through the incessant exchange of sand. Intense storm-wave processes erode the foredune within a few hours and transport its sand sand seaward, while aeolian processes return the eroded sand from the beach into the dune system, although at a much lower pace (months to years, or meso scale). Here we use an 8-year long data set of half-hourly snapshot video images, collected from an ≡ 50 m high tower on Egmond Beach (The Netherlands), and a concurrent meteorological and water level data set, to examine which factors affect aeolian sand delivery into the dunes. Egmond is a north-south oriented, micro- to meso-tidal, wave-dominated site that faces the North Sea. Its beach is relatively narrow ( ~ 100 m at spring low tide) and mildly sloping (~ 1 : 30), and consists of quartz sand with a median diameter of about 300 μm. Aeolian activity is clearly visible on the images as sand streamers and, in particular, sand strips, defined as low-amplitude, large-wavelength and slipfaceless deposits that migrate slowly in the wind direction and, depending on wind direction, can have orientations from almost shore-parallel to shore-normal. Beach width in combination with wind direction appeared to be the dominant factors in controlling aeolian activity. Many high wind (>≡ 13 m/s) events, especially from the west and northwest, were associated with a storm surge that inundated almost the entire beach with, accordingly, no possibility for aeolian transport. In contrast, sand-strip fields covered the entire beach during medium wind (≡ 12 - 13 m/s) events, especially when the wind was nearly shore-parallel. Many sand-strip events were observed to be regulated by the tide. Prominent sand-strip fields on the intertidal and upper beach were largely limited to low-tide situations with a wide beach, with a rising tide obviously destroying the intertidal sand strips and sometimes also negatively

  13. Scale Development for Measuring and Predicting Adolescents’ Leisure Time Physical Activity Behavior

    PubMed Central

    Ries, Francis; Romero Granados, Santiago; Arribas Galarraga, Silvia

    2009-01-01

    The aim of this study was to develop a scale for assessing and predicting adolescents’ physical activity behavior in Spain and Luxembourg using the Theory of Planned Behavior as a framework. The sample was comprised of 613 Spanish (boys = 309, girls = 304; M age =15.28, SD =1.127) and 752 Luxembourgish adolescents (boys = 343, girls = 409; M age = 14.92, SD = 1.198), selected from students of two secondary schools in both countries, with a similar socio-economic status. The initial 43-items were all scored on a 4-point response format using the structured alternative format and translated into Spanish, French and German. In order to ensure the accuracy of the translation, standardized parallel back-translation techniques were employed. Following two pilot tests and subsequent revisions, a second order exploratory factor analysis with oblimin direct rotation was used for factor extraction. Internal consistency and test-retest reliabilities were also tested. The 4-week test-retest correlations confirmed the items’ time stability. The same five factors were obtained, explaining 63.76% and 63.64% of the total variance in both samples. Internal consistency for the five factors ranged from α = 0.759 to α = 0. 949 in the Spanish sample and from α = 0.735 to α = 0.952 in the Luxembourgish sample. For both samples, inter-factor correlations were all reported significant and positive, except for Factor 5 where they were significant but negative. The high internal consistency of the subscales, the reported item test-retest reliabilities and the identical factor structure confirm the adequacy of the elaborated questionnaire for assessing the TPB-based constructs when used with a population of adolescents in Spain and Luxembourg. The results give some indication that they may have value in measuring the hypothesized TPB constructs for PA behavior in a cross-cultural context. Key points When using the structured alternative format, weak internal consistency was obtained

  14. The restricted promoter activity of the liver transcription factor hepatocyte nuclear factor 3 beta involves a cell-specific factor and positive autoactivation.

    PubMed Central

    Pani, L; Quian, X B; Clevidence, D; Costa, R H

    1992-01-01

    The transcription factor hepatocyte nuclear factor 3 (HNF-3) is involved in the coordinate expression of several liver genes. HNF-3 DNA binding activity is composed of three different liver proteins which recognize the same DNA site. The HNF-3 proteins (designated alpha, beta, and gamma) possess homology in the DNA binding domain and in several additional regions. To understand the cell-type-specific expression of HNF-3 beta, we have defined the regulatory sequences that elicit hepatoma-specific expression. Promoter activity requires -134 bp of HNF-3 beta proximal sequences and binds four nuclear proteins, including two ubiquitous factors. One of these promoter sites interacts with a novel cell-specific factor, LF-H3 beta, whose binding activity correlates with the HNF-3 beta tissue expression pattern. Furthermore, there is a binding site for the HNF-3 protein within its own promoter, suggesting that an autoactivation mechanism is involved in the establishment of HNF-3 beta expression. We propose that both the LF-H3 beta and HNF-3 sites play an important role in the cell-type-specific expression of the HNF-3 beta transcription factor. Images PMID:1732730

  15. Characterization of a cell-type-restricted negative regulatory activity of the human granulocyte-macrophage colony-stimulating factor gene.

    PubMed Central

    Fraser, J K; Guerra, J J; Nguyen, C Y; Indes, J E; Gasson, J C; Nimer, S D

    1994-01-01

    Human granulocyte-macrophage colony-stimulating factor (GM-CSF) stimulates the proliferation and maturation of normal myeloid progenitor cells and can also stimulate the growth of acute myelogenous leukemia (AML) blasts. GM-CSF is not normally produced by resting cells but is expressed by a variety of activated cells including T lymphocytes, macrophages, and certain cytokine-stimulated fibroblasts and endothelial cells. Production of GM-CSF by cultured AML cells has been demonstrated, and GM-CSF expression by normal myeloid progenitors has been postulated to play a role in myelopoiesis. We have investigated the regulation of expression of GM-CSF in AML cell lines, and our results demonstrate the presence of a strong constitutive promoter element contained within 53 bp upstream of the cap site. We have also identified a negative regulatory element located immediately upstream of the positive regulatory element (within 69 bp of the cap site) that is active in AML cell lines but not T cells or K562 CML cells. Competition transfection and mobility shift studies demonstrate that this activity correlates with binding of a 45-kDa protein. Images PMID:8114751

  16. Dietary restriction with and without caloric restriction for healthy aging

    PubMed Central

    Lee, Changhan; Longo, Valter

    2016-01-01

    Caloric restriction is the most effective and reproducible dietary intervention known to regulate aging and increase the healthy lifespan in various model organisms, ranging from the unicellular yeast to worms, flies, rodents, and primates. However, caloric restriction, which in most cases entails a 20–40% reduction of food consumption relative to normal intake, is a severe intervention that results in both beneficial and detrimental effects. Specific types of chronic, intermittent, or periodic dietary restrictions without chronic caloric restriction have instead the potential to provide a significant healthspan increase while minimizing adverse effects. Improved periodic or targeted dietary restriction regimens that uncouple the challenge of food deprivation from the beneficial effects will allow a safe intervention feasible for a major portion of the population. Here we focus on healthspan interventions that are not chronic or do not require calorie restriction. PMID:26918181

  17. Restrictive vs. non-restrictive composition: a magnetoencephalography study

    PubMed Central

    Leffel, Timothy; Lauter, Miriam; Westerlund, Masha; Pylkkänen, Liina

    2014-01-01

    Recent research on the brain mechanisms underlying language processing has implicated the left anterior temporal lobe (LATL) as a central region for the composition of simple phrases. Because these studies typically present their critical stimuli without contextual information, the sensitivity of LATL responses to contextual factors is unknown. In this magnetoencephalography (MEG) study, we employed a simple question-answer paradigm to manipulate whether a prenominal adjective or determiner is interpreted restrictively, i.e., as limiting the set of entities under discussion. Our results show that the LATL is sensitive to restriction, with restrictive composition eliciting higher responses than non-restrictive composition. However, this effect was only observed when the restricting element was a determiner, adjectival stimuli showing the opposite pattern, which we hypothesise to be driven by the special pragmatic properties of non-restrictive adjectives. Overall, our results demonstrate a robust sensitivity of the LATL to high level contextual and potentially also pragmatic factors. PMID:25379512

  18. Crustal-scale active deformation along the Ecuadorian Andes using Persistent Scatterers SAR Interferometry

    NASA Astrophysics Data System (ADS)

    Champenois, J.; Baize, S.; Audin, L.; Pinel, V.; Alvarado, A.; Jomard, H.; Yepes, H. A.

    2013-12-01

    Located in the Northern Andes along the active subduction zone of the Nazca plate beneath the South American continent, Ecuador is highly exposed to seismic hazard. For the last ten years, numerous multidisciplinary studies focused on major seismicity related to the subduction, whereas few investigations concentrated on M>7 crustal seismicity in the upper plate (like 1797 Riobamba earthquake, ML 8.3, 12.000 deaths). The active faults producing these earthquakes are poorly known in term of slip rate and for some cases are even not identified yet. Additionnally, Ecuador is one of the most active volcanic areas of the northern Andean volcanic zone. Three among the nine active volcanoes are actually erupting (Reventador, Tungurahua, and Sangay). For the last 5 years, geodetic networks have been deployed in Ecuador to enhance crustal deformation monitoring, but these point-wise techniques cannot provide spatially dense maps of ground deformation and are quite expensive methods. To address this issue, we applied the Persistent Scatterers SAR Interferometry technique (StaMPS/MTI freeware developed by A. Hooper) to ENVISAT SAR data between 2003 and 2009. Using these cost-effective techniques, we are able to investigate both tectonic and volcanic surface deformations with an unprecedented spatial density of measurements. This study presents new PS-InSAR results along the Ecuadorian Andes, close to the area of Riobamba. We generated average velocity maps and consistent time-series of displacements measured along the radar line of sight. These results evidence large scale deformation localized on the Pallatanga fault system (locked fault) compatible with a model of locked strike slip fault. Moreover, these results show an important growth of the Tungurahua volcanic complex (maximum rate about 9 mm/yr) with a rapid uplift prior and post 2006 explosive eruption. We investigate the time-series of displacement for 22 images. Our results permitted to propose two crustal source

  19. Spectral damping scaling factors for shallow crustal earthquakes in active tectonic regions

    USGS Publications Warehouse

    Rezaeian, Sanaz; Bozorgnia, Yousef; Idriss, I.M.; Campbell, Kenneth; Abrahamson, Norman; Silva, Walter

    2012-01-01

    Ground motion prediction equations (GMPEs) for elastic response spectra, including the Next Generation Attenuation (NGA) models, are typically developed at a 5% viscous damping ratio. In reality, however, structural and non-structural systems can have damping ratios other than 5%, depending on various factors such as structural types, construction materials, level of ground motion excitations, among others. This report provides the findings of a comprehensive study to develop a new model for a Damping Scaling Factor (DSF) that can be used to adjust the 5% damped spectral ordinates predicted by a GMPE to spectral ordinates with damping ratios between 0.5 to 30%. Using the updated, 2011 version of the NGA database of ground motions recorded in worldwide shallow crustal earthquakes in active tectonic regions (i.e., the NGA-West2 database), dependencies of the DSF on variables including damping ratio, spectral period, moment magnitude, source-to-site distance, duration, and local site conditions are examined. The strong influence of duration is captured by inclusion of both magnitude and distance in the DSF model. Site conditions are found to have less significant influence on DSF and are not included in the model. The proposed model for DSF provides functional forms for the median value and the logarithmic standard deviation of DSF. This model is heteroscedastic, where the variance is a function of the damping ratio. Damping Scaling Factor models are developed for the “average” horizontal ground motion components, i.e., RotD50 and GMRotI50, as well as the vertical component of ground motion.

  20. One-Hundred-km-Scale Basins on Enceladus: Evidence for an Active Ice Shell

    NASA Technical Reports Server (NTRS)

    Schenk, Paul M.; McKinnon, William B.

    2009-01-01

    Stereo-derived topographic mapping of 50% of Enceladus reveals at least 6 large-scale, ovoid depressions (basins) 90-175 km across and 800-to-1500 m deep and uncorrelated with geologic boundaries. Their shape and scale are inconsistent with impact, geoid deflection, or with dynamically supported topography. Isostatic thinning of Enceladus ice shell associated with upwellings (and tidally-driven ice melting) can plausibly account for the basins. Thinning implies upwarping of the base of the shell of 10-20 km beneath the depressions, depending on total shell thickness; loss of near-surface porosity due to enhanced heat flow may also contribute to basin lows. Alternatively, the basins may overly cold, inactive, and hence denser ice, but thermal isostasy alone requires thermal expansion more consistent with clathrate hydrate than water ice. In contrast to the basins, the south polar depression (SPD) is larger (350 wide) and shallower (0.4-to-0.8 km deep) and correlates with the area of tectonic deformation and active resurfacing. The SPD also differs in that the floor is relatively flat (i.e., conforms roughly to the global triaxial shape, or geoid) with broad, gently sloping flanks. The relative flatness across the SPD suggests that it is in or near isostatic equilibrium, and underlain by denser material, supporting the polar sea hypothesis of Collins and Goodman. Near flatness is also predicted by a crustal spreading origin for the "tiger stripes (McKinnon and Barr 2007, Barr 2008); the extraordinary, high CIRS heat flows imply half-spreading rates in excess of 10 cm/yr, a very young surface age (250,000 yr), and a rather thin lithosphere (hence modest thermal topography). Topographic rises in places along the outer margin of the SPD correlate with parallel ridges and deformation along the edge of the resurfaced terrain, consistent with a compressional, imbricate thrust origin for these ridges, driven by the spreading.