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. Maternal activity restriction and the prevention of preterm birth.

    PubMed

    Sciscione, Anthony C

    2010-03-01

    Activity restriction is 1 of the most common interventions used in obstetrics. Although it is used for many reasons, 1 of the most common is to prevent preterm birth in those at risk. This review of the literature describes the potential advantages, disadvantages, and efficacy of activity restriction for the prevention of preterm birth.

  3. Perceived risk of osteoporosis: Restricted physical activities?

    PubMed Central

    Dalsgaard Reventlow, Susanne

    2007-01-01

    Objective To explore elderly women's physical activity in relation to their perception of the risk of osteoporosis. Design Qualitative study using in-depth interviews. Setting Informants were purposely selected from a Danish population-based, age-specific cohort study conducted in the county of Copenhagen with people born in 1936. Subjects Women in their sixties. Results Women who perceived a current risk of osteoporosis tended to reduce their physical activity in an attempt to reduce the risk of bone damage. This behaviour was related to the imagined fragility of the bones (the risk inside the body), and the actual situations (the risk outside the body), including places and activities. Knowledge of a reduced bone mass reinforced the women's uncertainty about what their bones could endure. Experiences managing physical activity without injury resulted in reinterpretations of their risk of bone fractures and increased physical activity. Conclusions Perceived risk of osteoporosis may lead to decreased physical activity and hence actually increase the risk. When informing individuals about health risk people's images and imaginations of the actual risk have to be acknowledged. When a bone scan is being considered, explicit advice encouraging physical activity – especially the weight-bearing kind – should be stressed. PMID:17846934

  4. Response-restriction analysis: II. Alteration of activity preferences.

    PubMed Central

    Hanley, Gregory P; Iwata, Brian A; Roscoe, Eileen M; Thompson, Rachel H; Lindberg, Jana S

    2003-01-01

    We used response-restriction (RR) assessments to identify the preferences of 7 individuals with mental retardation for a variety of vocational and leisure activities. We subsequently increased their engagement in nonpreferred activities using several procedures: response restriction per se versus a Premack-type contingency (Study 1), supplemental reinforcement for engagement in target activities (Study 2), and noncontingent pairing of reinforcers with nonpreferred activities (Study 3). Results indicated that preferences are not immutable and can be altered through a variety of relatively benign interventions and that the results of RR assessments may be helpful in determining which types of procedures may be most effective on an individual basis. PMID:12723867

  5. Pleasant Events, Activity Restriction, and Blood Pressure in Dementia Caregivers

    PubMed Central

    Chattillion, Elizabeth A.; Ceglowski, Jenni; Roepke, Susan K.; von Känel, Roland; Losada, Andres; Mills, Paul J.; Romero-Moreno, Rosa; Grant, Igor; Patterson, Thomas L.; Mausbach, Brent T.

    2012-01-01

    Objective A combination of high engagement in pleasurable activities and low perceived activity restriction is potentially protective for a number of health and quality of life outcomes. This study tests the newly proposed Pleasant Events and Activity Restriction (PEAR) model to explain level of blood pressure (BP) in a sample of elderly dementia caregivers. Methods This cross-sectional study included 66 caregivers, ≥ 55 years of age, providing in-home care to a relative with dementia. Planned comparisons were made to assess group differences in BP between caregivers reporting high engagement in pleasant events plus low perceived activity restriction (HPLR; N = 22) to those with low pleasure plus high restriction (LPHR; N = 23) or those with either high pleasure plus high restriction or low pleasure plus low restriction (HPHR/LPLR; N = 21). Results After adjustments for age, sex, body mass index, use of anti-hypertensive medication, physical activity, and number of health problems, HPLR participants (86.78 mm Hg) had significantly lower mean arterial pressure compared to LPHR participants (94.70 mm Hg) (p = .01, Cohen’s d=0.89) and HPHR/LPLR participants (94.84 mm Hg) (p = .023, d=0.91). Similar results were found in post-hoc comparisons of both systolic and diastolic BP. Conclusions This study extends support for the PEAR model to physical health outcomes. Differences in BP between the HPLR group and other groups were of large magnitude and thus clinically meaningful. The findings may inform intervention studies aimed at investigating whether increasing pleasant events and lowering perceived activity restriction may lower BP. PMID:22888824

  6. 15 CFR 971.103 - Prohibited activities and restrictions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... of the following activities: (i) Scientific research, including that concerning hard mineral... claim in the United States or any other nation; and any other activity designed to harass, or which has...) Restrictions on issuance of permits. The Administrator will not issue any permit— (1) After the date on...

  7. 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…

  8. 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...

  9. 24 CFR 570.309 - Restriction on location of activities.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 24 Housing and Urban Development 3 2010-04-01 2010-04-01 false Restriction on location of activities. 570.309 Section 570.309 Housing and Urban Development Regulations Relating to Housing and Urban Development (Continued) OFFICE OF ASSISTANT SECRETARY FOR COMMUNITY PLANNING AND DEVELOPMENT, DEPARTMENT...

  10. Quantitative determination of effective nibbling activities contaminating restriction endonuclease preparations.

    PubMed

    Hashimoto-Gotoh, T

    1995-10-10

    A simple and sensitive procedure with which to detect residual exonucleolytic nibbling activities contaminating restriction endonuclease preparations is described. The procedure uses the kyosei-plasmid, pKF4, which confers kanamycin resistance and enforces streptomycin sensitivity encoded by the trp promoter/operator-driven rpsL+amber(PO(trp)-rpsL+4(am)) gene onto Escherichia coli streptomycin-resistant, amber-suppressive, trp repressor-negative strains such as TH5. When TH5 cells transformed by pKF4 were selected on agar medium containing kanamycin plus streptomycin, the efficiency of transformation plating was substantially lower than that on agar containing kanamycin alone. However, when pKF4 DNA was digested by restriction enzymes that cut once per molecule within PO(trp)-rpsL+4(am) and relegated, the plating efficiency increased depending on the degree of contamination of exonucleolytic nibbling activities in the enzyme preparations, due to deletion mutation at the ligand junction. Plating efficiency was converted to "effective nibbling activity" corresponding to Bal31 nuclease-equivalent units. Using this procedure, effective nibbling activities were detected in 17 of 34 commercial samples of restriction enzymes tested. The method is simple and more sensitive than the procedures used by the commercial suppliers and it is applicable to the quality control testing of more than 100 restriction enzymes.

  11. 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

  12. 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…

  13. 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.

  14. 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

  15. A criterion of orthogonality on the assumption and restrictions in subgrid-scale modelling of turbulence

    NASA Astrophysics Data System (ADS)

    Fang, L.; Sun, X. Y.; Liu, Y. W.

    2016-12-01

    In order to shed light on understanding the subgrid-scale (SGS) modelling methodology, we analyze and define the concepts of assumption and restriction in the modelling procedure, then show by a generalized derivation that if there are multiple stationary restrictions in a modelling, the corresponding assumption function must satisfy a criterion of orthogonality. Numerical tests using one-dimensional nonlinear advection equation are performed to validate this criterion. This study is expected to inspire future research on generally guiding the SGS modelling methodology.

  16. Effect of early feed restriction and enzyme supplementation on digestive enzyme activities in broilers.

    PubMed

    Pinheiro, D F; Cruz, V C; Sartori, J R; Vicentini Paulino, M L M

    2004-09-01

    The effect of feed restriction and enzymatic supplementation on intestinal and pancreatic enzyme activities and weight gain was studied in broiler chickens. Quantitative feed restriction was applied to chickens from 7 to 14 d of age. An enzyme complex mainly consisting of protease and amylase was added to the chicken ration from hatching to the end of the experiment. Birds subjected to feed restriction whose diet was not supplemented showed an increase in sucrase, amylase, and lipase activities immediately after the restriction period. Amylase, lipase, and chymotrypsin activities were higher in chickens subjected to feed restriction and fed a supplemented diet than in those only subjected to feed restriction. Trypsin activity increased after feed restriction and after supplementation, but there was no interaction between these effects. Early feed restriction had no effect on enzyme activity in 42-d-old chickens. Chickens subjected to early restriction and fed the supplemented diet presented higher sucrase, maltase, and lipase activities than nonsupplemented ones (P < 0.05). There was no effect of early feed restriction or diet supplementation on weight gain to 42 d. Percentage weight gain from 14 to 42 d of age was equivalent in feed-restricted and ad libitum fed birds. Feed-restricted broilers fed a supplemented diet showed a higher percentage weight gain than nonsupplemented birds. We conclude that enzymatic supplementation potentiates the effect of feed restriction on digestive enzyme activity and on weight gain.

  17. 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 OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE DANGER ZONE AND RESTRICTED AREA REGULATIONS § 334.761 Naval Support Activity Panama City; St. Andrews Bay; restricted areas. (a) The...

  18. 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...

  19. 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...

  20. 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.

  1. 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...

  2. 33 CFR 334.761 - Naval Support Activity Panama City; St. Andrews Bay; restricted areas.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 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...

  3. 33 CFR 334.763 - Naval Support Activity Panama City; Gulf of Mexico; restricted area.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 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 is... enforced by the Commanding Officer, Naval Support Activity, Panama City Florida, and such agencies as...

  4. 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 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...

  5. 33 CFR 334.763 - Naval Support Activity Panama City; Gulf of Mexico; restricted area.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 33 Navigation and Navigable Waters 3 2014-07-01 2014-07-01 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...

  6. Implementation of the velocity scaling method for elliptic restricted three-body problems

    NASA Astrophysics Data System (ADS)

    Wang, Shou-Cheng; Wu, Xin; Liu, Fu-Yao

    2016-12-01

    The velocity scaling method of Ma et al., as an extension of Nacozy's manifold correction scheme, can frequently take the solution of a numerical integration back to a surface determined by an integral of the equations of motion. An elliptic restricted three-body Hamiltonian of the Sun, major and minor planets in a rotating frame is explicitly dependent on time and, therefore, is not a conserved quantity. In this case, there is no Jacobi conservative integral available but there is a Jacobi non-conservative integral. This seems to be an obstacle to applying the velocity scaling correction method. Here are two points about an effective way to overcome this obstacle. First, because of the Hamiltonian having momentum- and coordinate-dependent terms associated with the contributions from the non-inertial frame, a scaling correction factor should be used to act on the velocities in the Jacobi non-conservative integral although the momenta are integration variables. Secondly, at each integration step, the value of the Hamiltonian obtained from an integral invariant relation is referred to as a more accurate reference value; the scaling factor versus the velocities is given by constraining the numerical solution to remain on the Jacobi non-conservative integral along this reference value. Numerical experiments show that a lower-order non-symplectic algorithm plus the velocity scaling scheme demonstrates good numerical performance in suppressing the rapid growth of integration errors, compared to the lower-order uncorrected algorithm. The correction scheme is powerful for eliminating spurious non-physical chaos due to integration errors. It is found that a larger eccentricity of the giant planet will increase the possibility of chaos or escape of the asteroid.

  7. 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.

  8. 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…

  9. The geriatric hand: correlation of hand-muscle function and activity restriction in elderly.

    PubMed

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

    2009-09-01

    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 function and activity restriction in the geriatric age group, through grip and pinch measurements and a set of questionnaires. Twenty-four geriatric (aged 65-79 years) volunteers participated in the study. Bilateral grip and pinch strengths have been recorded. To document impairment of manual functions, self-estimated hand function, Duruöz and Dreiser hand indices, Geriatrics-Arthritis Impact Measurement Scale (GERI-AIMS) manual dexterity questionnaires have been completed. Activity restriction and quality of life of these patients were inquired with short form (SF)-36 and Instrumental Activities of Daily Living (IADL) scores. Grip and pinch strengths correlated best with Duruöz and Dreiser indices. Similarly, SF-36 and IADL had higher correlation coefficients for Duruöz and Dreiser indices. A very good correlation between IADL and SF-36 was calculated too. Male and female participants revealed statistically significant differences for grip and pinch strengths as well as self-estimated hand function and SF-36. Another result was that none of our parameters, including grip strength and SF-36 had differed significantly between the 65-70 and 70-79 years age subgroups. However, grip strength displayed statistically significant lower values when compared with young adult mean values of a previous study. Our data in this study support the hypothesis that hand-muscle function correlates with functional dependency in the elderly. Manual function can be determined by grip strength in addition to multiple available functional tools. In this study, Dreiser and Duruöz hand function indices were the best to correlate with ADL and

  10. 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

  11. Public Relations and Propaganda: Restrictions on Executive Agency Activities

    DTIC Science & Technology

    2005-03-21

    executive branch agencies’ expenditures of appropriated funds on public relations activities, some of which have been characterized as propagandistic...Congress may ask the Government Accountability Office (GAO) to examine an agency’s expenditures on public relations activities with a view to their...7 Tracking Expenditures

  12. Emergence and scaling of synchronization in moving-agent networks with restrictive interactions

    NASA Astrophysics Data System (ADS)

    Kim, Beomseok; Do, Younghae; Lai, Ying-Cheng

    2013-10-01

    In fields such as robotics and sensor networks, synchronization among mobile and dynamic agents is a basic task. We articulate an effective strategy to achieve synchronization in dynamic networks of moving chaotic agents. Our counterintuitive idea is to restrict agents’ ability to interact with each other, which can be implemented by designating a finite number of fixed zones in the space, in which agents are allowed to interact with each other but agents outside the zones are deprived of the ability of mutual interaction. Our setting is thus different from the one used in existing works on synchronization of mobile agents where each agent is associated with an interacting zone that moves with the agent. We find, through a mathematical analysis, that an optimal interval exists in the interaction probability, where stable synchronization emerges. An inverse square-root scaling law is uncovered which relates the interval with the system size, i.e., the total number of moving agents. Extensive numerical support for physical spaces of one, two, and three dimensions is provided.

  13. Activity Restriction and Depression in Medical Patients and their Caregivers: A Meta Analysis

    PubMed Central

    Mausbach, Brent T; Chattillion, Elizabeth A; Moore, Raeanne C; Roepke, Susan K; Depp, Colin A; Roesch, Scott

    2011-01-01

    Depression commonly occurs in conjunction with a variety of medical conditions. In addition, family members who care for patients with medical diagnoses often suffer from depression. Therefore, in addition to treating illnesses, physicians and other healthcare professionals are often faced with managing secondary mental health consequences. We conducted a systematic review and meta-analysis of the association between activity restriction and depression in medical patients and their caregivers. A total of 34 studies (N = 8,053) documenting the relationship between activity restriction and depression were identified for the period between January 1980 and June 2010. Effect sizes were calculated as Pearson r correlations using random-effects models. The correlation between activity restriction and depression was positive and of large magnitude (r = 0.39; 95% CI, .34–.44). Activity restriction was most strongly correlated with depression in medical patients (r = 0.45; 95% CI, 0.42–0.48), followed by caregivers (r = 0.34; 95% CI, 0.28–0.41) and community-dwelling adults (r = 0.28; 95% CI, 0.25–0.31). Activity restriction associated with medical conditions is a significant threat to well-being and quality of life, as well as to the lives of their caregivers. Assessment and treatment of activity restriction may be particularly helpful in preventing depression. PMID:21600868

  14. 15 CFR 970.103 - Prohibited activities and restrictions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 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...

  15. 15 CFR 970.103 - Prohibited activities and restrictions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 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...

  16. 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...

  17. 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...

  18. 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...

  19. 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.

  20. Effect of neck flexion restriction on sternocleidomastoid and abdominal muscle activity during curl-up exercises.

    PubMed

    Lee, Dong-Kyu; Moon, Dong-Chul; Hong, Ki-Hoon

    2016-01-01

    [Purpose] The purpose of this study was to investigate the effect of neck flexion restriction on sternocleidomastoid (SCM), rectus abdominis (RA), and external oblique (EO) muscle activity during a traditional curl-up exercise and a curl-up with neck flexion restriction. [Subjects] In total, 13 healthy male subjects volunteered for this study. [Methods] All subjects performed a traditional curl-up exercise and a curl-up exercise in which neck flexion was restricted by the subject's hand. Surface electromyography (EMG) signals were recorded from the SCM, RA, and EO during the curl-up. [Results] There was significantly lower EMG activity of the SCM during the curl-up exercise with neck flexion restriction compared to the traditional curl-up exercise. Conversely, the activity of the RA and EO muscles was significantly higher in the curl-up exercise with neck flexion restriction than in the traditional curl-up exercise. [Conclusion] Neck flexion restriction is recommended to prevent excessive activation of superficial cervical flexors during the curl-up exercise.

  1. Effect of neck flexion restriction on sternocleidomastoid and abdominal muscle activity during curl-up exercises

    PubMed Central

    Lee, Dong-Kyu; Moon, Dong-Chul; Hong, Ki-Hoon

    2016-01-01

    [Purpose] The purpose of this study was to investigate the effect of neck flexion restriction on sternocleidomastoid (SCM), rectus abdominis (RA), and external oblique (EO) muscle activity during a traditional curl-up exercise and a curl-up with neck flexion restriction. [Subjects] In total, 13 healthy male subjects volunteered for this study. [Methods] All subjects performed a traditional curl-up exercise and a curl-up exercise in which neck flexion was restricted by the subject’s hand. Surface electromyography (EMG) signals were recorded from the SCM, RA, and EO during the curl-up. [Results] There was significantly lower EMG activity of the SCM during the curl-up exercise with neck flexion restriction compared to the traditional curl-up exercise. Conversely, the activity of the RA and EO muscles was significantly higher in the curl-up exercise with neck flexion restriction than in the traditional curl-up exercise. [Conclusion] Neck flexion restriction is recommended to prevent excessive activation of superficial cervical flexors during the curl-up exercise. PMID:26957735

  2. Protein aggregation activates erratic stress response in dietary restricted yeast cells

    PubMed Central

    Bhadra, Ankan Kumar; Das, Eshita; Roy, Ipsita

    2016-01-01

    Chronic stress and prolonged activation of defence pathways have deleterious consequences for the cell. Dietary restriction is believed to be beneficial as it induces the cellular stress response machinery. We report here that although the phenomenon is beneficial in a wild-type cell, dietary restriction leads to an inconsistent response in a cell that is already under proteotoxicity-induced stress. Using a yeast model of Huntington’s disease, we show that contrary to expectation, aggregation of mutant huntingtin is exacerbated and activation of the unfolded protein response pathway is dampened under dietary restriction. Global proteomic analysis shows that when exposed to a single stress, either protein aggregation or dietary restriction, the expression of foldases like peptidyl-prolyl isomerase, is strongly upregulated. However, under combinatorial stress, this lead is lost, which results in enhanced protein aggregation and reduced cell survival. Successful designing of aggregation-targeted therapeutics will need to take additional stressors into account. PMID:27633120

  3. 15 CFR 712.2 - Restrictions on activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... Schedule 1 chemicals. 712.2 Section 712.2 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.2 Restrictions on activities...

  4. 15 CFR 712.2 - Restrictions on activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... Schedule 1 chemicals. 712.2 Section 712.2 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.2 Restrictions on activities...

  5. 15 CFR 712.2 - Restrictions on activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... Schedule 1 chemicals. 712.2 Section 712.2 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.2 Restrictions on activities...

  6. 15 CFR 712.2 - Restrictions on activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Schedule 1 chemicals. 712.2 Section 712.2 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL WEAPONS CONVENTION REGULATIONS ACTIVITIES INVOLVING SCHEDULE 1 CHEMICALS § 712.2 Restrictions on activities...

  7. Molecular Links between Caloric Restriction and Sir2/SIRT1 Activation

    PubMed Central

    2014-01-01

    Ageing is the most significant risk factor for a range of prevalent diseases, including cancer, cardiovascular disease, and diabetes. Accordingly, interventions are needed for delaying or preventing disorders associated with the ageing process, i.e., promotion of healthy ageing. Calorie restriction is the only nongenetic and the most robust approach to slow the process of ageing in evolutionarily divergent species, ranging from yeasts, worms, and flies to mammals. Although it has been known for more than 80 years that calorie restriction increases lifespan, a mechanistic understanding of this phenomenon remains elusive. Yeast silent information regulator 2 (Sir2), the founding member of the sirtuin family of protein deacetylases, and its mammalian homologue Sir2-like protein 1 (SIRT1), have been suggested to promote survival and longevity of organisms. SIRT1 exerts protective effects against a number of age-associated disorders. Caloric restriction increases both Sir2 and SIRT1 activity. This review focuses on the mechanistic insights between caloric restriction and Sir2/SIRT1 activation. A number of molecular links, including nicotinamide adenine dinucleotide, nicotinamide, biotin, and related metabolites, are suggested to be the most important conduits mediating caloric restriction-induced Sir2/SIRT1 activation and lifespan extension. PMID:25349818

  8. 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…

  9. 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 CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE DANGER ZONE AND RESTRICTED AREA REGULATIONS § 334.762 Naval Support Activity Panama City; North Bay and West Bay; restricted areas. (a)...

  10. 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 CORPS OF ENGINEERS, DEPARTMENT OF THE ARMY, DEPARTMENT OF DEFENSE DANGER ZONE AND RESTRICTED AREA REGULATIONS § 334.762 Naval Support Activity Panama City; North Bay and West Bay; restricted areas. (a)...

  11. A Pronounced Inflammatory Activity Characterizes the Early Fracture Healing Phase in Immunologically Restricted Patients.

    PubMed

    Hoff, Paula; Gaber, Timo; Strehl, Cindy; Jakstadt, Manuela; Hoff, Holger; Schmidt-Bleek, Katharina; Lang, Annemarie; Röhner, Eric; Huscher, Dörte; Matziolis, Georg; Burmester, Gerd-Rüdiger; Schmidmaier, Gerhard; Perka, Carsten; Duda, Georg N; Buttgereit, Frank

    2017-03-08

    Immunologically restricted patients such as those with autoimmune diseases or malignancies often suffer from delayed or insufficient fracture healing. In human fracture hematomas and the surrounding bone marrow obtained from immunologically restricted patients, we analyzed the initial inflammatory phase on cellular and humoral level via flow cytometry and multiplex suspension array. Compared with controls, we demonstrated higher numbers of immune cells like monocytes/macrophages, natural killer T (NKT) cells, and activated T helper cells within the fracture hematomas and/or the surrounding bone marrow. Also, several pro-inflammatory cytokines such as Interleukin (IL)-6 and Tumor necrosis factor α (TNFα), chemokines (e.g., Eotaxin and RANTES), pro-angiogenic factors (e.g., IL-8 and Macrophage migration inhibitory factor: MIF), and regulatory cytokines (e.g., IL-10) were found at higher levels within the fracture hematomas and/or the surrounding bone marrow of immunologically restricted patients when compared to controls. We conclude here that the inflammatory activity on cellular and humoral levels at fracture sites of immunologically restricted patients considerably exceeds that of control patients. The initial inflammatory phase profoundly differs between these patient groups and is probably one of the reasons for prolonged or insufficient fracture healing often occurring within immunologically restricted patients.

  12. A Pronounced Inflammatory Activity Characterizes the Early Fracture Healing Phase in Immunologically Restricted Patients

    PubMed Central

    Hoff, Paula; Gaber, Timo; Strehl, Cindy; Jakstadt, Manuela; Hoff, Holger; Schmidt-Bleek, Katharina; Lang, Annemarie; Röhner, Eric; Huscher, Dörte; Matziolis, Georg; Burmester, Gerd-Rüdiger; Schmidmaier, Gerhard; Perka, Carsten; Duda, Georg N.; Buttgereit, Frank

    2017-01-01

    Immunologically restricted patients such as those with autoimmune diseases or malignancies often suffer from delayed or insufficient fracture healing. In human fracture hematomas and the surrounding bone marrow obtained from immunologically restricted patients, we analyzed the initial inflammatory phase on cellular and humoral level via flow cytometry and multiplex suspension array. Compared with controls, we demonstrated higher numbers of immune cells like monocytes/macrophages, natural killer T (NKT) cells, and activated T helper cells within the fracture hematomas and/or the surrounding bone marrow. Also, several pro-inflammatory cytokines such as Interleukin (IL)-6 and Tumor necrosis factor α (TNFα), chemokines (e.g., Eotaxin and RANTES), pro-angiogenic factors (e.g., IL-8 and Macrophage migration inhibitory factor: MIF), and regulatory cytokines (e.g., IL-10) were found at higher levels within the fracture hematomas and/or the surrounding bone marrow of immunologically restricted patients when compared to controls. We conclude here that the inflammatory activity on cellular and humoral levels at fracture sites of immunologically restricted patients considerably exceeds that of control patients. The initial inflammatory phase profoundly differs between these patient groups and is probably one of the reasons for prolonged or insufficient fracture healing often occurring within immunologically restricted patients. PMID:28282868

  13. 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

  14. 12 CFR 303.207 - Restricted activities for critically undercapitalized institutions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... further the purposes of section 38 of the FDI Act (12 U.S.C. 1831o): (1) Enter into any material... Federal Reserve Act (12 U.S.C. 371c(b)); (6) Pay excessive compensation or bonuses. Part 364 of this... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Restricted activities for...

  15. 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…

  16. 15 CFR 712.2 - Restrictions on activities involving Schedule 1 chemicals.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 2 2011-01-01 2011-01-01 false Restrictions on activities involving Schedule 1 chemicals. 712.2 Section 712.2 Commerce and Foreign Trade Regulations Relating to Commerce and Foreign Trade (Continued) BUREAU OF INDUSTRY AND SECURITY, DEPARTMENT OF COMMERCE CHEMICAL...

  17. 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.

  18. 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

  19. Activation of geminivirus V-sense promoters in roots is restricted to nematode feeding sites.

    PubMed

    Escobar, Carolina; García, Alejandra; Aristizábal, Fabio; Portillo, Mary; Herreros, Esther; Munoz-Martín, M Angeles; Grundler, Florian; Mullineaux, Phillip M; Fenoll, Carmen

    2010-05-01

    Obligate sedentary endoparasitic nematodes, such as the root-knot and cyst nematodes, elicit the differentiation of specialized nematode nurse or feeding cells [nematode feeding sites (NFS), giant cells and syncytia, respectively]. During NFS differentiation, marked changes in cell cycle progression occur, partly similar to those induced by some geminiviruses. In this work, we describe the activation of V-sense promoters from the Maize streak virus (MSV) and Wheat dwarf virus (WDV) in NFS formed by root-knot and cyst nematodes. Both promoters were transiently active in microinjection experiments. In tobacco and Arabidopsis transgenic lines carrying promoter-beta-glucuronidase fusions, the MSV V-sense promoter was activated in the vascular tissues of aerial plant parts, primarily leaf and cotyledon phloem tissue and some floral structures. Interestingly, in roots, promoter activation was restricted to syncytia and giant cells tested with four different nematode populations, but undetectable in the rest of the root system. As the activity of the promoter in transgenic rootstocks should be restricted to NFS only, the MSV promoter may have utility in engineering grafted crops for nematode control. Therefore, this study represents a step in the provision of some of the much needed additional data on promoters with restricted activation in NFS useful in biotechnological nematode control strategies.

  20. 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.

  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. Disruption of running activity rhythm following restricted feeding in female mice: Preventive effects of antidepressants.

    PubMed

    Miyawaki, Kazumi; Araki, Hiroaki; Yoshimura, Hiroyuki

    2015-03-01

    Biological rhythms are critical in the etiology of mood disorders; therefore, effective mood disorder treatments should address rhythm disturbances. Among the variables synchronized with the light-dark cycle, spontaneous activity in rodents is useful for investigating circadian rhythms. However, previous studies have focused only on the increase of wheel-running activity under restricted feeding conditions, while little information is available on circadian rhythm of running activity. In this study, chronometrical analysis was used to assess whether circadian rhythms during wheel-running are altered by restricted feeding and affected by antidepressant drugs. Wheel revolutions were automatically recorded and analyzed using cosinor-rhythmometry in 8-week old ICR albino mice. When feeding was restricted to 1 h per day (21:00-22:00), wheel-running rhythms were reliably disrupted. Female mice exhibited marked alterations in the pattern and extent of wheel-running beginning on day 1. Subchronic treatment with imipramine or paroxetine, as well as tandospirone and (-)-DOI, prevented wheel-running rhythm disruption. Thus, altering the circadian activity rhythms of female mice on a 1-h feeding schedule may be useful for investigating disturbances in biological rhythms.

  3. 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…

  4. 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....

  5. Successful removal of zinc sulfide scale restriction from a hot, deep, sour gas well

    SciTech Connect

    Kenrick, A.J.; Ali, S.A.

    1997-07-01

    Removal of zinc sulfide scale with hydrochloric acid from a hot, deep, Norphlet Sandstone gas well in the Gulf of Mexico resulted in a 29% increase in the production rates. The zinc sulfide scale was determined to be in the near-wellbore area. The presence of zinc sulfide is explained by the production of 25 ppm H{sub 2}S gas, and the loss of 50--100 bbl of zinc bromide fluid to the formation. Although zinc sulfide scale has been successfully removed with hydrochloric acid in low-to-moderate temperature wells, no analogous treatment data were available for high temperature, high pressure (HTHP) Norphlet wells. Therefore laboratory testing was initiated to identify suitable acid systems for scale removal, and select a high quality corrosion inhibitor that would mitigate detrimental effects of the selected acid on downhole tubulars and surface equipment. This case history presents the first successful use of hydrochloric acid in removing zinc sulfide scale from a HTHP Norphlet sour gas well.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. Scaling laws of human interaction activity.

    PubMed

    Rybski, Diego; Buldyrev, Sergey V; Havlin, Shlomo; Liljeros, Fredrik; Makse, Hernán A

    2009-08-04

    Even though people in our contemporary technological society are depending on communication, our understanding of the underlying laws of human communicational behavior continues to be poorly understood. Here we investigate the communication patterns in 2 social Internet communities in search of statistical laws in human interaction activity. This research reveals that human communication networks dynamically follow scaling laws that may also explain the observed trends in economic growth. Specifically, we identify a generalized version of Gibrat's law of social activity expressed as a scaling law between the fluctuations in the number of messages sent by members and their level of activity. Gibrat's law has been essential in understanding economic growth patterns, yet without an underlying general principle for its origin. We attribute this scaling law to long-term correlation patterns in human activity, which surprisingly span from days to the entire period of the available data of more than 1 year. Further, we provide a mathematical framework that relates the generalized version of Gibrat's law to the long-term correlated dynamics, which suggests that the same underlying mechanism could be the source of Gibrat's law in economics, ranging from large firms, research and development expenditures, gross domestic product of countries, to city population growth. These findings are also of importance for designing communication networks and for the understanding of the dynamics of social systems in which communication plays a role, such as economic markets and political systems.

  11. 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.

  12. The LIM Protein Ajuba Restricts the Second Heart Field Progenitor Pool by Regulating Isl1 Activity

    PubMed Central

    Witzel, Hagen R.; Jungblut, Benno; Choe, Chong Pyo; Crump, J. Gage; Braun, Thomas; Dobreva, Gergana

    2013-01-01

    SUMMARY Morphogenesis of the heart requires tight control of cardiac progenitor cell specification, expansion, and differentiation. Retinoic acid (RA) signaling restricts expansion of the second heart field (SHF), serving as an important morphogen in heart development. Here, we identify the LIM domain protein Ajuba as a crucial regulator of the SHF progenitor cell specification and expansion. Ajuba-deficient zebra-fish embryos show an increased pool of Isl1+ cardiac progenitors and, subsequently, dramatically increased numbers of cardiomyocytes at the arterial and venous poles. Furthermore, we show that Ajuba binds Isl1, represses its transcriptional activity, and is also required for autorepression of Isl1 expression in an RA-dependent manner. Lack of Ajuba abrogates the RA-dependent restriction of Isl1+ cardiac cells. We conclude that Ajuba plays a central role in regulating the SHF during heart development by linking RA signaling to the function of Isl1, a key transcription factor in cardiac progenitor cells. PMID:22771034

  13. 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

  14. Factors That Moderate Activity Limitation and Participation Restriction in People With Multiple Sclerosis.

    PubMed

    Goverover, Yael; Strober, Lauren; Chiaravalloti, Nancy; DeLuca, John

    2015-01-01

    We examined the variables most associated with activity limitation (i.e., cooking) and participation restriction (i.e., employment) in 72 people with multiple sclerosis (MS). Participants underwent a comprehensive neuropsychological test battery assessing memory, executive functions, visual perception, and processing speed and completed questionnaires assessing activity, participation, fatigue, and affective symptoms. Results showed that processing speed was the only variable consistently significantly related to both activity and participation. When examining specific aspects of activity and participation in isolation, employment status was significantly associated with education level, visual memory, fatigue, and processing speed. Cooking ability was associated with performance on tasks of working memory, verbal memory, and processing speed. These findings suggest that processing speed is a primary cognitive factor in MS influencing quality of both activity and participation in everyday life.

  15. Qualitative analysis of sequence specific binding of flavones to DNA using restriction endonuclease activity assays.

    PubMed

    Duran, Elizabeth; Ramsauer, Victoria P; Ballester, Maria; Torrenegra, Ruben D; Rodriguez, Oscar E; Winkle, Stephen A

    2013-08-01

    Flavones, found in nature as secondary plant metabolites, have shown efficacy as anti-cancer agents. We have examined the binding of two flavones, 5,7-dihydroxy-3,6,8-trimethoxy-2-phenyl-4H-chromen-4-one (5,7-dihydroxy-3,6,8-trimethoxy flavone; FlavA) and 3,5-dihydroxy-6,7,8-trimethoxy-2-phenyl-4H-chromen-4-one (3,5-dihydroxy-6,7,8-trimethoxy flavone; FlavB), to phiX174 RF DNA using restriction enzyme activity assays employing the restriction enzymes Alw44, AvaII, BssHII, DraI, MluI, NarI, NciI, NruI, PstI, and XhoI. These enzymes possess differing target and flanking sequences allowing for observation of sequence specificity analysis. Using restriction enzymes that cleave once with a mixture of supercoiled and relaxed DNA substrates provides for observation of topological effects on binding. FlavA and FlavB show differing sequence specificities in their respective binding to phiX. For example, with relaxed DNA, FlavA shows inhibition of cleavage with DraI (reaction site (5') TTTAAA) but not BssHII ((5') GCGCGC) while FlavB shows the opposite results. Evidence for tolological specificity is also observed, Molecular modeling and conformational analysis of the flavones suggests that the phenyl ring of FlavB is coplanar with the flavonoid ring while the phenyl ring of FlavA is at an angle relative to the flavonoid ring. This may account for aspects of the observed sequence and topological specificities in the effects on restriction enzyme activity.

  16. A Highly Active Isoform of Lentivirus Restriction Factor SAMHD1 in Mouse.

    PubMed

    Bloch, Nicolin; Gläsker, Sabine; Sitaram, Poojitha; Hofmann, Henning; Shepard, Caitlin N; Schultz, Megan L; Kim, Baek; Landau, Nathaniel R

    2017-01-20

    The triphosphohydrolase SAMHD1 (sterile α motif and histidine-aspartate domain-containing protein 1) restricts HIV-1 replication in nondividing myeloid cells by depleting the dNTP pool, preventing reverse transcription. SAMHD1 is also reported to have ribonuclease activity that degrades the virus genomic RNA. Human SAMHD1 is regulated by phosphorylation of its carboxyl terminus at Thr-592, which abrogates its antiviral function yet has only a small effect on its phosphohydrolase activity. In the mouse, SAMHD1 is expressed as two isoforms (ISF1 and ISF2) that differ at the carboxyl terminus due to alternative splicing of the last coding exon. In this study we characterized the biochemical and antiviral properties of the two mouse isoforms of SAMHD1. Both are antiviral in nondividing cells. Mass spectrometry analysis showed that SAMHD1 is phosphorylated at several amino acid residues, one of which (Thr-634) is homologous to Thr-592. Phosphomimetic mutation at Thr-634 of ISF1 ablates its antiviral activity yet has little effect on phosphohydrolase activity in vitro dGTP caused ISF1 to tetramerize, activating its catalytic activity. In contrast, ISF2, which lacks the phosphorylation site, was significantly more active, tetramerized, and was active without added dGTP. Neither isoform nor human SAMHD1 had detectable RNase activity in vitro or affected HIV-1 genomic RNA stability in newly infected cells. These data support a model in which SAMHD1 catalytic activity is regulated through tetramer stabilization by the carboxyl-terminal tail, phosphorylation destabilizing the complexes and inactivating the enzyme. ISF2 may serve to reduce the dNTP pool to very low levels as a means of restricting virus replication.

  17. 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.

  18. Vitamin E Restriction in the Diet Enhances Phagocytic Activation by Dichloroacetate and Trichloroacetate in Mice

    PubMed Central

    Hassoun, Ezdihar A.; Al-Dieri, Ali

    2011-01-01

    The effects of a Vitamin E-restricted diet on the induction of phagocytic activation by dichloro-acetate (DCA) and trichloroacetate (TCA) was investigated. Groups of B6C3F1 male mice were either kept on standard diet (Std diet group) or diet that had the vitamin provided only by its natural ingredients (Low-E diet group). The animals in each diet group were administered 77 mg of DCA or TCA/ kg/day, or 5 ml/kg water (controls), by gavage, for 13 weeks. Thereafter, peritoneal lavage cells (PLC) were assayed for superoxide anion (SA), tumor necrosis factor (TNF)-α, and myeloperoxidase (MPO), as well as for the activities of the anti-oxidant enzymes superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GSH-Px). SA and TNFα production, as well as MPO, SOD, CAT and GSH-Px activities were significantly increased in the cells from the Low-E diet group treated with the compounds as compared with cells from hosts in the Std-diet group that received the corresponding treatments. The results indicate that consumption of a Vitamin E-restricted diet enhances the induction of phagocytic activation by DCA and TCA, a mechanism that was previously suggested to be an initial adaptive/protective response against the compounds long-term effects. PMID:22178223

  19. The fragment structure of a putative HsdR subunit of a type I restriction enzyme from Vibrio vulnificus YJ016: implications for DNA restriction and translocation activity

    PubMed Central

    Uyen, Nguyen To; Park, Suk-Youl; Choi, Ji-Woo; Lee, Hyun-Ju; Nishi, Kosuke; Kim, Jeong-Sun

    2009-01-01

    Among four types of bacterial restriction enzymes that cleave a foreign DNA depending on its methylation status, type I enzymes composed of three subunits are interesting because of their unique DNA cleavage and translocation mechanisms performed by the restriction subunit (HsdR). The elucidated N-terminal fragment structure of a putative HsdR subunit from Vibrio vulnificus YJ016 reveals three globular domains. The nucleolytic core within an N-terminal nuclease domain (NTD) is composed of one basic and three acidic residues, which include a metal-binding site. An ATP hydrolase (ATPase) site at the interface of two RecA-like domains (RDs) is located close to the probable DNA-binding site for translocation, which is far from the NTD nucleolytic core. Comparison of relative domain arrangements with other functionally related ATP and/or DNA complex structures suggests a possible translocation and restriction mechanism of the HsdR subunit. Furthermore, careful analysis of its sequence and structure implies that a linker helix connecting two RDs and an extended region within the nuclease domain may play a central role in switching the DNA translocation into the restriction activity. PMID:19625490

  20. 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.

  1. Effects of restrictive clothing on lumbar range of motion and trunk muscle activity in young adult worker manual material handling.

    PubMed

    Eungpinichpong, Wichai; Buttagat, Vitsarut; Areeudomwong, Pattanasin; Pramodhyakul, Noppol; Swangnetr, Manida; Kaber, David; Puntumetakul, Rungthip

    2013-11-01

    The objective of this study was to examine the effect of wearing restrictive trousers on lumbar spine movement, trunk muscle activity and low back discomfort (LBD) in simulations of manual material handling (MMH) tasks. Twenty-eight young adults participated in the study performing box lifting, liquid container handling while squatting, and forward reaching while sitting on a task chair when wearing tight pants (sizes too small for the wearer) vs. fit pants (correct size according to anthropometry). Each task was repeated three times and video recordings were used as a basis for measuring lumbar range of motion (LRoM). The response was normalized in terms on baseline hip mobility. Trunk muscle activity of rectus abdominis (RA) and erector spinae (ES) muscles were also measured in each trial and normalized. At the close of each trial, participants rated LBD using a visual analog scale. Results revealed significant effects of both pants and task types on the normalized LRoM, trunk muscle activity and subjective ratings of LBD. The LRoM was higher and trunk muscle (ES) activity was lower for participants when wearing tight pants, as compared to fit pants. Discomfort ratings were significantly higher for tight pants than fit. These results provide guidance for recommendations on work clothing fit in specific types of MMH activities in order to reduce the potential of low-back pain among younger workers in industrial companies.

  2. 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…

  3. Low replacement doses of thyroxine during food restriction restores type 1 deiodinase activity in rats and promotes body protein loss.

    PubMed

    Araujo, Renata Lopes; de Andrade, Bruno Moulin; de Figueiredo, Alvaro Souto Padron; da Silva, Monique Leandro; Marassi, Michelle Porto; Pereira, Valmara dos Santos; Bouskela, Eliete; Carvalho, Denise P

    2008-07-01

    During food restriction, decreased basal metabolic rate secondary to reduced serum thyroid hormones levels contributes to weight loss resistance. Thyroxine (T(4)) and 3,3',5-tri-iodothyronine (T(3)) administration during caloric restriction produce deleterious side effects; however, the administration of physiological doses of T(4) during food restriction has never been evaluated. The aim of this study was to analyze the effects of low replacement doses of T(4) in Wistar rats subjected to 40% food restriction. Food restriction for 30 days led to significantly reduced liver type 1 deiodinase activity, serum TSH, leptin, T(4), T(3), metabolic rate, and body mass. The significant reduction in hepatic deiodinase activity found during food restriction was normalized in a dose-dependent manner by T(4) replacement, showing that decreased type 1 deiodinase (D1) activity is secondary to decreased serum thyroid hormone levels during caloric restriction. The lowest replacement dose of T(4) did not normalize resting metabolic rate, but was able to potentiate the effects of food restriction on carcass fat loss and did not spare body protein. The highest dose of T(4) produced a normalization of daily oxygen consumption and determined a significant reduction in both carcass fat and protein content. Our results show that serum T(4) normalization during food restriction restores serum T(3) and liver D1 activity, while body protein is not spared. Thus, decreased serum T(4) during caloric restriction corresponds to a protective mechanism to avoid body protein loss, highlighting the importance of other strategies to reduce body mass without lean mass loss.

  4. 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.

  5. Site-restricted plasminogen activation mediated by group A streptococcal streptokinase variants.

    PubMed

    Cook, Simon M; Skora, Amanda; Walker, Mark J; Sanderson-Smith, Martina L; McArthur, Jason D

    2014-02-15

    SK (streptokinase) is a secreted plasminogen activator and virulence factor of GAS (group A Streptococcus). Among GAS isolates, SK gene sequences are polymorphic and are grouped into two sequence clusters (cluster type-1 and cluster type-2) with cluster type-2 being further classified into subclusters (type-2a and type-2b). In the present study, we examined the role of bacterial and host-derived cofactors in SK-mediated plasminogen activation. All SK variants, apart from type-2b, can form an activator complex with Glu-Plg (Glu-plasminogen). Specific ligand-binding-induced conformational changes in Glu-Plg mediated by fibrinogen, PAM (plasminogen-binding group A streptococcal M protein), fibrinogen fragment D or fibrin, were required for type-2b SK to form a functional activator complex with Glu-Plg. In contrast with type-1 and type-2a SK, type-2b SK activator complexes were inhibited by α2-antiplasmin unless bound to fibrin or to the GAS cell-surface via PAM in combination with fibrinogen. Taken together, these data suggest that type-2b SK plasminogen activation may be restricted to specific microenvironments within the host such as fibrin deposits or the bacterial cell surface through the action of α2-antiplasmin. We conclude that phenotypic SK variation functionally underpins a pathogenic mechanism whereby SK variants differentially focus plasminogen activation, leading to specific niche adaption within the host.

  6. 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

    2013-09-05

    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.

  7. Asymmetric hydration structure around calcium ion restricted in micropores fabricated in activated carbons

    NASA Astrophysics Data System (ADS)

    Ohkubo, Takahiro; Kusudo, Tomoko; Kuroda, Yasushige

    2016-11-01

    The adsorbed phase and hydration structure of an aqueous solution of Ca(NO3)2 restricted in micropores fabricated in activated carbons (ACs) having different average pore widths (0.63 and 1.1 nm) were investigated with the analysis of adsorption isotherms and x-ray absorption fine structure (XAFS) spectra on Ca K-edge. The adsorbed density of Ca2+ per unit micropore volume in the narrower pore was higher than in the wider pore, while the adsorbed amount per unit mass of carbon with the narrower pore was half of the amount of ACs with the larger pore. On the other hand, variations in the bands assigned to double-electron (KM I) and 1s  →  3d excitations in XAFS spectra demonstrate the formation of a distorted hydration cluster around Ca2+ in the micropore, although the structural parameters of hydrated Ca2+ in the micropores were almost consistent with the bulk aqueous solution, as revealed by the analysis of extended XAFS (EXAFS) spectra. In contrast to the hydration structure of monovalent ions such as Rb+, which generally presents a dehydrated structure in smaller than 1 nm micropores in ACs, the present study clearly explains that the non-spherically-symmetric structure of hydrated Ca2+ restricted in carbon micropores whose sizes are around 1 nm is experimentally revealed where any dehydration phenomena from the first hydration shell around Ca2+ could not be observed.

  8. On the role of steric clashes in methylation control of restriction endonuclease activity

    PubMed Central

    Mierzejewska, Karolina; Bochtler, Matthias; Czapinska, Honorata

    2016-01-01

    Restriction-modification systems digest non-methylated invading DNA, while protecting host DNA against the endonuclease activity by methylation. It is widely believed that the methylated DNA would not ‘fit’ into the binding site of the endonuclease in the productive orientation, and thus steric clashes should account for most of the protection. We test this concept statistically by grafting methyl groups in silico onto non-methylated DNA in co-crystal structures with restriction endonucleases. Clash scores are significantly higher for protective than non-protective methylation (P < 0.05% according to the Wilcoxon rank sum test). Structural data alone are sufficient to distinguish between protective and non-protective DNA methylation with 90% confidence and decision thresholds of 1.1 Å and 48 Å3 for the most severe distance-based and cumulative volume-based clash with the protein, respectively (0.1 Å was deducted from each interatomic distance to allow for coordinate errors). The most severe clashes are more pronounced for protective methyl groups attached to the nitrogen atoms (N6-methyladenines and N4-methylcytosines) than for C5-methyl groups on cytosines. Cumulative clashes are comparable for all three types of protective methylation. PMID:26635397

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

    PubMed

    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

    2014-06-03

    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.

  10. Screening for catalytically active Type II restriction endonucleases using segregation-induced methylation deficiency

    PubMed Central

    Ukanis, Mindaugas; Sapranauskas, Rimantas; Lubys, Arvydas

    2012-01-01

    Type II restriction endonucleases (REases) are one of the basic tools of recombinant DNA technology. They also serve as models for elucidation of mechanisms for both site-specific DNA recognition and cleavage by proteins. However, isolation of catalytically active mutants from their libraries is challenging due to the toxicity of REases in the absence of protecting methylation, and techniques explored so far had limited success. Here, we present an improved SOS induction-based approach for in vivo screening of active REases, which we used to isolate a set of active variants of the catalytic mutant, Cfr10IE204Q. Detailed characterization of plasmids from 64 colonies screened from the library of ∼200 000 transformants revealed 29 variants of cfr10IR gene at the level of nucleotide sequence and 15 variants at the level of amino acid sequence, all of which were able to induce SOS response. Specific activity measurements of affinity-purified mutants revealed >200-fold variance among them, ranging from 100% (wild-type isolates) to 0.5% (S188C mutant), suggesting that the technique is equally suited for screening of mutants possessing high or low activity and confirming that it may be applied for identification of residues playing a role in catalysis. PMID:22753027

  11. 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

    2016-04-04

    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.

  12. Impairments, activity limitations, and participation restrictions of the international classification of functioning, disability, and health model in children with ambulatory cerebral palsy

    PubMed Central

    Mutlu, Akmer; Büğüsan, Sema; Kara, Özgün K.

    2017-01-01

    Objectives: To examine the impairments, activity limitations, and participation restrictions in children with spastic unilateral and bilateral cerebral palsy (CP). We investigated the relationship between these factors according to the international classification of functioning, disability, and health (ICF) model. Methods: This prospective cross sectional study included 60 children aged between 4-18 years with spastic CP (30 unilateral, 30 bilateral involvement) classified as Levels I and II on the gross motor function classification system. Children had been referred to the Pediatric Rehabilitation Unit in the Department of Physiotherapy and Rehabilitation, Hacettepe University, Ankara, Turkey between March 2014 and March 2015. The Physician Rating scale was used to assess body functions and structures. The Gillette Functional Assessment Questionnaire 22-item skill set, Pediatric Functional Independence Measure, and Pediatric Outcomes Data Collection Instrument were used to assess activity and participation levels. Results: There was a significant positive correlation between impairments and activity limitations (r=0.558; p=0.000), as well as between activity limitations and participation restrictions (r=0.354, p=0.005). Conclusion: These results show that activity limitations in children with unilateral and bilateral ambulatory CP may be related to their impairments and participation restrictions, although the sample size of our study is not large enough for generalizations. Overall, our study highlights the need for up-to-date, practical evaluation methods according to the ICF model. PMID:28133691

  13. 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.

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

    SciTech Connect

    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 investigate 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.

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

    DOE PAGES

    Martins, Murillo L.; Ignazzi, Rosanna; Eckert, Juergen; ...

    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

  16. Follicular B cell trafficking within the spleen actively restricts humoral immune responses

    PubMed Central

    Hoek, Kristen L.; Gordy, Laura E.; Collins, Patrick L.; Parekh, Vrajesh V.; Aune, Thomas M.; Joyce, Sebastian; Thomas, James W.; Van Kaer, Luc; Sebzda, Eric

    2010-01-01

    Summary Follicular (FO) and marginal zone (MZ) B cells are maintained in distinct locations within the spleen but the genetic basis for this separation is still enigmatic. We now report that B cell sequestration requires lineage-specific regulation of migratory receptors by the transcription factor, Klf2. Moreover, using gene-targeted mice we show that altered splenic B cell migration confers a significant in vivo gain-of-function phenotype to FO B cells, including the ability to quickly respond to MZ-associated antigens and pathogens in a T cell-dependent manner. This work demonstrates that in wild-type animals, naïve FO B cells are actively removed from the MZ, thus restricting their capacity to respond to blood-borne pathogens. PMID:20691614

  17. 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

  18. Small molecule activators of SIRT1 replicate signaling pathways triggered by calorie restriction in vivo

    PubMed Central

    Smith, Jesse J; Kenney, Renée Deehan; Gagne, David J; Frushour, Brian P; Ladd, William; Galonek, Heidi L; Israelian, Kristine; Song, Jeffrey; Razvadauskaite, Giedre; Lynch, Amy V; Carney, David P; Johnson, Robin J; Lavu, Siva; Iffland, Andre; Elliott, Peter J; Lambert, Philip D; Elliston, Keith O; Jirousek, Michael R; Milne, Jill C; Boss, Olivier

    2009-01-01

    Background Calorie restriction (CR) produces a number of health benefits and ameliorates diseases of aging such as type 2 diabetes. The components of the pathways downstream of CR may provide intervention points for developing therapeutics for treating diseases of aging. The NAD+-dependent protein deacetylase SIRT1 has been implicated as one of the key downstream regulators of CR in yeast, rodents, and humans. Small molecule activators of SIRT1 have been identified that exhibit efficacy in animal models of diseases typically associated with aging including type 2 diabetes. To identify molecular processes induced in the liver of mice treated with two structurally distinct SIRT1 activators, SIRT501 (formulated resveratrol) and SRT1720, for three days, we utilized a systems biology approach and applied Causal Network Modeling (CNM) on gene expression data to elucidate downstream effects of SIRT1 activation. Results Here we demonstrate that SIRT1 activators recapitulate many of the molecular events downstream of CR in vivo, such as enhancing mitochondrial biogenesis, improving metabolic signaling pathways, and blunting pro-inflammatory pathways in mice fed a high fat, high calorie diet. Conclusion CNM of gene expression data from mice treated with SRT501 or SRT1720 in combination with supporting in vitro and in vivo data demonstrates that SRT501 and SRT1720 produce a signaling profile that mirrors CR, improves glucose and insulin homeostasis, and acts via SIRT1 activation in vivo. Taken together these results are encouraging regarding the use of small molecule activators of SIRT1 for therapeutic intervention into type 2 diabetes, a strategy which is currently being investigated in multiple clinical trials. PMID:19284563

  19. Influence of conformationally restricted pyrimidines on the activity of 10-23 DNAzymes.

    PubMed

    Robaldo, Laura; Izzo, Franco; Dellafiore, María; Proietti, Cecilia; Elizalde, Patricia V; Montserrat, Javier M; Iribarren, Adolfo M

    2012-04-15

    The catalytic core of a 10-23 DNAzyme was modified introducing conformationally restricted nucleosides such as (2'R)-, (2'S)-2'-deoxy-2'-C-methyluridine, (2'R)-, (2'S)-2'-deoxy-2'-C-methylcytidine, 2,2'-anhydrouridine and LNA-C, in one, two or three positions. Catalytic activities under pseudo first order conditions were compared at different Mg(2+) concentrations using a short RNA substrate. At low Mg(2+) concentrations, triple modified DNAzymes with similar kinetic performance to that displayed by the non-modified control were identified. In the search for a partial explanation of the obtained results, in silico studies were carried out in order to explore the conformational behavior of 2'-deoxy-2'-C-methylpyrimidines in the context of a loop structure, suggesting that at least partial flexibility is needed for the maintenance of activity. Finally, the modified 2'-C-methyl DNAzyme activity was tested assessing the inhibition of Stat3 expression and the decrease in cell proliferation using the human breast cancer cell line T47D.

  20. 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.

  1. Intestinal PPARγ signalling is required for sympathetic nervous system activation in response to caloric restriction

    PubMed Central

    Duszka, Kalina; Picard, Alexandre; Ellero-Simatos, Sandrine; Chen, Jiapeng; Defernez, Marianne; Paramalingam, Eeswari; Pigram, Anna; Vanoaica, Liviu; Canlet, Cécile; Parini, Paolo; Narbad, Arjan; Guillou, Hervé; Thorens, Bernard; Wahli, Walter

    2016-01-01

    Nuclear receptor PPARγ has been proven to affect metabolism in multiple tissues, and has received considerable attention for its involvement in colon cancer and inflammatory disease. However, its role in intestinal metabolism has been largely ignored. To investigate this potential aspect of PPARγ function, we submitted intestinal epithelium-specific PPARγ knockout mice (iePPARγKO) to a two-week period of 25% caloric restriction (CR), following which iePPARγKO mice retained more fat than their wild type littermates. In attempting to explain this discrepancy, we analysed the liver, skeletal muscle, intestinal lipid trafficking, and the microbiome, none of which appeared to contribute to the adiposity phenotype. Interestingly, under conditions of CR, iePPARγKO mice failed to activate their sympathetic nervous system (SNS) and increase CR-specific locomotor activity. These KO mice also manifested a defective control of their body temperature, which was overly reduced. Furthermore, the white adipose tissue of iePPARγKO CR mice showed lower levels of both hormone-sensitive lipase, and its phosphorylated form. This would result from impaired SNS signalling and possibly cause reduced lipolysis. We conclude that intestinal epithelium PPARγ plays an essential role in increasing SNS activity under CR conditions, thereby contributing to energy mobilization during metabolically stressful episodes. PMID:27853235

  2. Mimetics of caloric restriction include agonists of lipid-activated nuclear receptors.

    PubMed

    Corton, J Christopher; Apte, Udayan; Anderson, Steven P; Limaye, Pallavi; Yoon, Lawrence; Latendresse, John; Dunn, Corrie; Everitt, Jeffrey I; Voss, Kenneth A; Swanson, Cynthia; Kimbrough, Carie; Wong, Jean S; Gill, Sarjeet S; Chandraratna, Roshantha A S; Kwak, Mi-Kyoung; Kensler, Thomas W; Stulnig, Thomas M; Steffensen, Knut R; Gustafsson, Jan-Ake; Mehendale, Harihara M

    2004-10-29

    The obesity epidemic in industrialized countries is associated with increases in cardiovascular disease (CVD) and certain types of cancer. In animal models, caloric restriction (CR) suppresses these diseases as well as chemical-induced tissue damage. These beneficial effects of CR overlap with those altered by agonists of nuclear receptors (NR) under control of the fasting-responsive transcriptional co-activator, peroxisome proliferator-activated co-activator 1alpha (PGC-1alpha). In a screen for compounds that mimic CR effects in the liver, we found statistically significant overlaps between the CR transcript profile in wild-type mice and the profiles altered by agonists of lipid-activated NR, including peroxisome proliferator-activated receptor alpha (PPARalpha), liver X receptor, and their obligate heterodimer partner, retinoid X receptor. The overlapping genes included those involved in CVD (lipid metabolism and inflammation) and cancer (cell fate). Based on this overlap, we hypothesized that some effects of CR are mediated by PPARalpha. As determined by transcript profiling, 19% of all gene expression changes in wild-type mice were dependent on PPARalpha, including Cyp4a10 and Cyp4a14, involved in fatty acid omega-oxidation, acute phase response genes, and epidermal growth factor receptor but not increases in PGC-1alpha. CR protected the livers of wild-type mice from damage induced by thioacetamide, a liver toxicant and hepatocarcinogen. CR protection was lost in PPARalpha-null mice due to inadequate tissue repair. These results demonstrate that PPARalpha mediates some of the effects of CR and indicate that a pharmacological approach to mimicking many of the beneficial effects of CR may be possible.

  3. Dietary calcium restriction affects mesenchymal stem cell activity and bone development in neonatal pigs.

    PubMed

    Mahajan, Avanika; Alexander, Lindsey S; Seabolt, Brynn S; Catrambone, Daniel E; McClung, James P; Odle, Jack; Pfeiler, T Wayne; Loboa, Elizabeth G; Stahl, Chad H

    2011-03-01

    The effects of dietary calcium (Ca) deficiency on skeletal integrity are well characterized in growing and mature mammals; however, less is known about Ca nutrition during the neonatal period. In this study, we examined the effects of neonatal Ca nutrition on bone integrity, endocrine hormones, and mesenchymal stem cell (MSC) activity. Neonatal pigs (24 ± 6 h of age) received either a Ca-adequate (1.2 g/100 g) or an ~40% Ca-deficient diet for 18 d. Ca deficiency reduced (P < 0.05) bone flexural strength and bone mineral density without major differences in plasma indicators of Ca status. There were no meaningful differences in plasma Ca, phosphate (PO(4)), parathyroid hormone, or 1,25-dihydroxycholecalciferol due to Ca nutrition throughout the study. Calcium deficiency also reduced (P < 0.05) the in vivo proliferation of MSC by ~50%. In vitro studies utilizing homologous sera demonstrated that MSC activity was affected (P < 0.05) by both the Ca status of the pig and the sera as well as by their interaction. The results indicate that neonatal Ca nutrition is crucial for bone integrity and suggest that early-life Ca restriction may have long-term effects on bone integrity via programming of MSC.

  4. Let's Not Waste Time: Using Temporal Information in Clustered Activity Estimation with Spatial Adjacency Restrictions (CAESAR) for Parcellating FMRI Data.

    PubMed

    Janssen, Ronald J; Jylänki, Pasi; van Gerven, Marcel A J

    2016-01-01

    We have proposed a Bayesian approach for functional parcellation of whole-brain FMRI measurements which we call Clustered Activity Estimation with Spatial Adjacency Restrictions (CAESAR). We use distance-dependent Chinese restaurant processes (dd-CRPs) to define a flexible prior which partitions the voxel measurements into clusters whose number and shapes are unknown a priori. With dd-CRPs we can conveniently implement spatial constraints to ensure that our parcellations remain spatially contiguous and thereby physiologically meaningful. In the present work, we extend CAESAR by using Gaussian process (GP) priors to model the temporally smooth haemodynamic signals that give rise to the measured FMRI data. A challenge for GP inference in our setting is the cubic scaling with respect to the number of time points, which can become computationally prohibitive with FMRI measurements, potentially consisting of long time series. As a solution we describe an efficient implementation that is practically as fast as the corresponding time-independent non-GP model with typically-sized FMRI data sets. We also employ a population Monte-Carlo algorithm that can significantly speed up convergence compared to traditional single-chain methods. First we illustrate the benefits of CAESAR and the GP priors with simulated experiments. Next, we demonstrate our approach by parcellating resting state FMRI data measured from twenty participants as taken from the Human Connectome Project data repository. Results show that CAESAR affords highly robust and scalable whole-brain clustering of FMRI timecourses.

  5. 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

  6. Impact of 6-month caloric restriction on autonomic nervous system activity in healthy, overweight, individuals.

    PubMed

    de Jonge, Lilian; Moreira, Emilia A M; Martin, Corby K; Ravussin, Eric

    2010-02-01

    Caloric restriction (CR) increases maximum lifespan but the mechanisms are unclear. Dominance of the sympathetic nervous system (SNS) over the parasympathetic nervous system (PNS) has been shown to be a strong risk factor for cardiovascular disease. Obesity and aging are associated with increased SNS activity, and weight loss and/or exercise seem to have positive effects on this balance. We therefore evaluated the effect of different approaches of CR on autonomic function in 28 overweight individuals participating in the Comprehensive Assessment of Long-term Effects of Reducing Intake of Energy (CALERIE) trial. Participants were randomized to either control, CR: 25% decrease in energy intake, CREX: 12.5% CR + 12.5% increase in energy expenditure, or LCD: low-calorie diet until 15% weight reduction followed by weight maintenance. Autonomic function was assessed by spectral analysis of heart-rate variability (HRV) while fasting and after a meal. Measurements were performed at baseline and 6 months. HR and SNS index decreased and PNS index increased in all intervention groups but reached significance only in CREX. HR and SNS index increased and PNS index decreased in response to the meal in all intervention groups. The results therefore suggest that weight loss improved SNS/PNS balance especially when CR is combined with exercise.

  7. Effect of restricted suckling on ovarian activity and uterine involution in Brahman cows.

    PubMed

    Bastidas, P; Trocóniz, J; Verde, O; Silva, O

    1984-04-01

    Seventy-six Brahman cows and first-calf heifers ranging in age from three to five or more years were used to determine the effects of restricted suckling on postpartum ovarian activity and uterine involution. At 30 days postcalving, cows were randomly assigned to one of two groups: 1)normal suckling (34 cows) and 2)twice-daily suckling (42 cows). The cows were examined by rectal palpation weekly from parturition until the onset of the breeding season. The average interval from parturition to the presence of the first follicle larger than 10 mm (PPFI) was 36.0 +/- 1.0 days, and twice-daily suckling decreased PPFI length 8.1 days (P < 0.01); likewise, first- and second-calf heifers tended to have longer PPFI length (P < 0.05) than cows with three or more calvings. The average interval from parturition to first corpus luteum (PPCLI) was 59.0 +/- 2.0 days. PPCLI was affected by the age (P < 0.05) and weight of the cow at 30 days postpartum (P < 0.10). The average interval from parturition to first estrus (PPEI) was 68.0 +/- 5.0 days. PPEI was affected by suckling (P < 0.10) and month of parturition (P < 0.05). The average interval from parturition to uterine involution was 33.0 +/- 1.0 days. Uterine involution was influenced by month of calving (P < 0.01) and age of the cow (P < 0.05).

  8. Herpes simplex virus 1 counteracts tetherin restriction via its virion host shutoff activity.

    PubMed

    Zenner, Helen L; Mauricio, Rui; Banting, George; Crump, Colin M

    2013-12-01

    The interferon-inducible membrane protein tetherin (Bst-2, or CD317) is an antiviral factor that inhibits enveloped virus release by cross-linking newly formed virus particles to the producing cell. The majority of viruses that are sensitive to tetherin restriction appear to be those that acquire their envelopes at the plasma membrane, although many viruses, including herpesviruses, envelope at intracellular membranes, and the effect of tetherin on such viruses has been less well studied. We investigated the tetherin sensitivity and possible countermeasures of herpes simplex virus 1 (HSV-1). We found that overexpression of tetherin inhibits HSV-1 release and that HSV-1 efficiently depletes tetherin from infected cells. We further show that the virion host shutoff protein (Vhs) is important for depletion of tetherin mRNA and protein and that removal of tetherin compensates for defects in replication and release of a Vhs-null virus. Vhs is known to be important for HSV-1 to evade the innate immune response in vivo. Taken together, our data suggest that tetherin has antiviral activity toward HSV-1 and that the removal of tetherin by Vhs is important for the efficient replication and dissemination of HSV-1.

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

    PubMed

    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.

  10. A nutrient-sensitive restriction point is active during retinal progenitor cell differentiation

    PubMed Central

    Love, Nicola K.; Keshavan, Nandaki; Lewis, Rebecca; Harris, William A.; Agathocleous, Michalis

    2014-01-01

    In many growing tissues, slowly dividing stem cells give rise to rapidly proliferating progenitors that eventually exit the cell cycle and differentiate. Growth rates are limited by nutrient availability, but it is unclear which steps of the proliferation-differentiation programme are particularly sensitive to fuel supplies. We examined how nutrient deprivation (ND) affects stem and progenitor cells in the ciliary marginal zone (CMZ) of the amphibian retina, a well-characterised neurogenic niche. We show that ND specifically blocks the proliferation and differentiation of progenitor cells through an mTOR-mediated mechanism. By contrast, the identity and proliferation of retinal stem cells are insensitive to ND and mTOR inhibition. Re-feeding starved retinas in vitro rescues both proliferation and differentiation, and activation of mTOR is sufficient to stimulate differentiation even in ND retinas. These results suggest that an mTOR-mediated restriction point operates in vivo to couple nutrient abundance to the proliferation and differentiation programme in retinal progenitor cells. PMID:24449845

  11. 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…

  12. 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.

  13. 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.

  14. Activity limitations and participation restrictions in women with hand osteoarthritis: patients' descriptions and associations between dimensions of functioning

    PubMed Central

    Kjeken, I; Dagfinrud, H; Slatkowsky-Christ..., B; Mowinckel, P; Uhlig, T; Kvien, T; Finset, A

    2005-01-01

    Objective: To describe the functional consequences of hand osteoarthritis, and analyse associations between personal factors, hand impairment, activity limitations, and participation restrictions within the framework of the International Classification of Functioning (ICF). Methods: 87 women with hand osteoarthritis completed a clinical examination including recording of sociodemographic data, measures of hand impairment, and completion of self reported health status measures. The function subscale of the AUSCAN Osteoarthritis Hand Index was used as a measure of hand related activity limitations, while the Canadian Occupational Performance Measure (COPM) was used to describe and measure activity limitations and participation restrictions as perceived by the individual. The study variables were categorised using the dimensions in the ICF framework and analysed using bivariate and multivariate statistical approaches. Results: The patients described problems in many domains of activity and participation. The most frequently described hand related problems were activities requiring considerable grip strength combined with twisting of the hands. On the impairment level, the patients had reduced grip force and joint mobility in the hands, and resisted motion was painful. Regression analyses showed that hand related activity limitations were associated with measures of hand impairment, while activity and participation (as measured by the COPM) were more strongly associated with personal factors than with hand impairment. Conclusions: Hand osteoarthritis has important functional consequences in terms of pain, reduced hand mobility and grip force, activity limitations, and participation restrictions. Rehabilitation programmes should therefore be multidisciplinary and multidimensional, focusing on hand function, occupational performance, and coping strategies. PMID:15829571

  15. 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...

  16. 45 CFR 2550.90 - Are there any restrictions on the activities of the members of State Commissions or Alternative...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 45 Public Welfare 4 2013-10-01 2013-10-01 false Are there any restrictions on the activities of the members of State Commissions or Alternative Administrative Entities? 2550.90 Section 2550.90 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND...

  17. 45 CFR 2550.90 - Are there any restrictions on the activities of the members of State Commissions or Alternative...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 45 Public Welfare 4 2014-10-01 2014-10-01 false Are there any restrictions on the activities of the members of State Commissions or Alternative Administrative Entities? 2550.90 Section 2550.90 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND...

  18. 45 CFR 2550.90 - Are there any restrictions on the activities of the members of State Commissions or Alternative...

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 45 Public Welfare 4 2012-10-01 2012-10-01 false Are there any restrictions on the activities of the members of State Commissions or Alternative Administrative Entities? 2550.90 Section 2550.90 Public Welfare Regulations Relating to Public Welfare (Continued) CORPORATION FOR NATIONAL AND...

  19. 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

  20. 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

  1. 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.

  2. Time-dependent restricted-active-space self-consistent-field theory with space partition

    NASA Astrophysics Data System (ADS)

    Miyagi, Haruhide; Madsen, Lars Bojer

    2017-02-01

    Aiming at efficient numerical analysis of time-dependent (TD) many-electron dynamics of atoms involving multielectron continua, the TD restricted-active-space self-consistent-field theory with space partition (TD-RASSCF-SP) is presented. The TD-RASSCF-SP wave function is expanded in terms of TD configuration-interaction coefficients with Slater determinants composed of two kinds of TD orbitals: M ̂ orbitals are defined to be nonvanishing in the inner region (V ̂), a small volume around the atomic nucleus, and M ˇ orbitals are nonvanishing in the large outer region (V ˇ). For detailed discussion of the SP strategy, the equations of motion are derived by two different formalisms for comparison. To ensure continuous differentiability of the wave function across the two regions, one of the formalisms makes use of the property of the finite-element discrete-variable-representation (FEDVR) functions and introduces additional time-independent orbitals. The other formalism is more general and is based on the Bloch operator as in the R -matrix theory, but turns out to be less practical for numerical applications. Hence, using the FEDVR-based formalism, the numerical performance is tested by computing double-ionization dynamics of atomic beryllium in intense light fields. To achieve high accuracy, M ̂ should be set large to take into account the strong many-electron correlation around the nucleus. On the other hand, M ˇ can be set much smaller than M ̂ for capturing the weaker correlation between the two outgoing photoelectrons. As a result, compared with more accurate multiconfigurational TD Hartree-Fock (MCTDHF) method, the TD-RASSCF-SP method may achieve comparable accuracy in the description of the double-ionization dynamics. There are, however, difficulties related to the stiffness of the equations of motion of the TD-RASSCF-SP method, which makes the required time step for this method smaller than the one needed for the MCTDHF approach.

  3. An inhibitory activity in human cells restricts the function of an avian-like influenza virus polymerase.

    PubMed

    Mehle, Andrew; Doudna, Jennifer A

    2008-08-14

    Transmission of avian influenza virus into human populations has the potential to cause pandemic outbreaks. A major determinant of species tropism is the identity of amino acid 627 in the PB2 subunit of the heterotrimeric influenza polymerase; glutamic acid predominates in avian PB2, whereas lysine occupies this position in human isolates. We show that a dominant inhibitory activity in human cells potently and selectively restricts the function of polymerases containing an avian-like PB2 with glutamic acid at residue 627. Restricted polymerases fail to assemble into ribonucleoprotein complexes, resulting in decreased genome transcription, replication, and virus production without any significant effect on relative viral infectivity. Understanding the molecular basis of this species-specific restriction should provide strategies to prevent and treat avian influenza outbreaks in humans.

  4. 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

  5. Effect of Methionine Restriction on Bone Density and NK Cell Activity

    PubMed Central

    Dong, Jingming

    2016-01-01

    Methionine restriction (MR) is proven to increase the lifespan; and it also affects the bone density and the innate immune system. The aim of this study is to explore the effect of methionine restriction on bone density and natural killer (NK) cells. C57BL/6J mice were subjected to either basal diet (BD, containing 0.80% methionine) or methionine-restricted diet (containing 0.14% methionine). Mice with MR diet displayed reduced bone mass and decrease in the cytotoxicity of NK from the spleen, compared to BD animals. Also, mice with MR diet had an inferior body weight (P < 0.05) and higher plasma levels of adiponectin and FGF21 (P < 0.05) but lower concentrations of leptin and IGF-1 (P < 0.05). Overall, the investigation shows that methionine affects bone density and NK cell cytotoxicity. PMID:27882323

  6. 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...

  7. Acute effects of blood flow restriction on muscle activity and endurance during fatiguing dynamic knee extensions at low load.

    PubMed

    Wernbom, Mathias; Järrebring, Rickard; Andreasson, Mikael A; Augustsson, Jesper

    2009-11-01

    The purpose of this study was to investigate muscle activity and endurance during fatiguing low-intensity dynamic knee extension exercise with and without blood flow restriction. Eleven healthy subjects with strength training experience performed 3 sets of unilateral knee extensions with no relaxation between repetitions to concentric torque failure at 30% of the 1 repetition maximum. One leg was randomized to exercise with cuff occlusion and the other leg to exercise without occlusion. The muscle activity in the quadriceps was recorded with electromyography (EMG). Ratings of perceived exertion (RPE) and acute pain were collected immediately, and delayed onset muscle soreness (DOMS) was rated before and at 24, 48, and 72 hours after exercise. The results demonstrated high EMG levels in both experimental conditions, but there were no significant differences regarding maximal muscle activity, except for a higher EMG in the eccentric phase in set 3 for the nonoccluded condition (p = 0.005). Significantly more repetitions were performed with the nonoccluded leg in every set (p < 0.05). The RPE and acute pain ratings were similar, but DOMS was higher in the nonoccluded leg (p < 0.05). We conclude that blood flow restriction during low-intensity dynamic knee extension decreases the endurance but does not increase the maximum muscle activity compared with training without restriction when both regimes are performed to failure. The high levels of muscle activity suggest that performing low-load dynamic knee extensions in a no-relaxation manner may be a useful method in knee rehabilitation settings when large forces are contraindicated. However, similarly to fatiguing blood flow restricted exercise, this method is associated with ischemic muscle pain, and thus its applications may be limited to highly motivated individuals.

  8. Restricted active space spin-flip configuration interaction: theory and examples for multiple spin flips with odd numbers of electrons.

    PubMed

    Zimmerman, Paul M; Bell, Franziska; Goldey, Matthew; Bell, Alexis T; Head-Gordon, Martin

    2012-10-28

    The restricted active space spin flip (RAS-SF) method is extended to allow ground and excited states of molecular radicals to be described at low cost (for small numbers of spin flips). RAS-SF allows for any number of spin flips and a flexible active space while maintaining pure spin eigenfunctions for all states by maintaining a spin complete set of determinants and using spin-restricted orbitals. The implementation supports both even and odd numbers of electrons, while use of resolution of the identity integrals and a shared memory parallel implementation allow for fast computation. Examples of multiple-bond dissociation, excited states in triradicals, spin conversions in organic multi-radicals, and mixed-valence metal coordination complexes demonstrate the broad usefulness of RAS-SF.

  9. Exercise restrictions trigger psychological difficulty in active and athletic adults with hypertrophic cardiomyopathy

    PubMed Central

    Luiten, Rebecca C; Ormond, Kelly; Post, Lisa; Asif, Irfan M; Wheeler, Matthew T; Caleshu, Colleen

    2016-01-01

    Objective We examined the extent and nature of the psychological difficulty experienced by athletic adults with hypertrophic cardiomyopathy (HCM), correlates of that difficulty and coping mechanisms. Methods A survey assessed athletic history and psychological impact of exercise restrictions. LASSO penalised linear regression identified factors associated with psychological difficulty. Semistructured interviews provided deeper insight into the nature and origins of psychological difficulty. Results 54 individuals (33% female, mean age 55.9) completed the survey. The majority were recreational athletes at the time of restriction (67%). There was a drop in athleticism after diagnosis, including time spent exercising (p=0.04) and identification as an athlete (p=0.0005). Most respondents (54%) found it stressful and/or difficult to adjust to exercise restrictions. Greater psychological morbidity was associated with history of elite or competitive athletics, athletic identity and decrease in time spent exercising. 16 individuals (44% female, mean age 52.4) were interviewed. Long-term effects included weight gain and uncertainty about exercising safely. The role of exercise in interviewees' lives contracted significantly after restriction, from multiple functions (eg, social, stress relief, fitness) to solely health maintenance. Interviewees reported a unique form of social support: having family and friends participate with them in lower intensity exercise. Lack of understanding from family or friends and avoiding exercise completely were detrimental to coping. Conclusions Athletic adults with HCM experience multifaceted, lasting difficulty adjusting to exercise recommendations. These data can guide clinicians in identifying patients at highest risk for distress and in helping to bolster coping and adaptation. PMID:27843566

  10. The Extent of Restrictions on the Service of Active-Component Military Women

    DTIC Science & Technology

    2012-01-01

    plans (see Table C.2 in Appendix C for details). The type and magnitude of gender restrictions based on unit closures differs by rank group. Marine...privacy for Sailors. The Navy reports that there are currently no plans to modify submarine berthing during routine maintenance to accommodate both men...Liaison Officers Naval gunfire liaison officers advise force commanders on naval gunfire support, plan and direct gunfire support, and carry out

  11. Mothers impose physical activity restrictions on their asthmatic children and adolescents: an analytical cross-sectional study

    PubMed Central

    2014-01-01

    Background Physical activities are important for children and adolescents, especially asthmatics. A significant proportion is considered less active than their non-asthmatic peers and mother’s beliefs about asthma are thought to be a determinant factor. The research objectives were to investigate whether mothers try to impose limitations on the physical activity (PA) of their asthmatic children/adolescents; identify associated factors; and explore if this attitude has any impact on children’s PA levels. Methods In this cross sectional investigation, we studied 115 asthmatics aged between 9 and 19 years and their mothers. Asthma severity, PA level and exercise induced bronchospasm (EIB) were evaluated. Mothers were questioned on their beliefs about physical activity in non-asthmatic and asthmatic children, if they imposed restrictions on their children’s physical activity, on EIB perception and personal levels of anxiety and depression. Results Ninety six percent of the mothers answered that PA are important for children and adolescents. Despite this, 37% of them admitted imposing restrictions to their children’s PA. This attitude was associated with mother’s negative opinions about asthmatics doing PA, perception of children’s dyspnea after running on a treadmill, mother’s anxiety level and children’s asthma severity. The mother’s restrictive attitudes were not associated with children’s lower PA levels. Conclusion A high proportion of the mothers said that they restrained their asthmatic children from engaging in physical activity. This fact should be recognized by health professionals and discussed with parents and caregivers as these negative beliefs may lead to conflicts and prejudiced attitudes that could discourage children’s involvement in physical activities and sports. PMID:24673939

  12. Fluctuation scaling of quotation activities in the foreign exchange market

    NASA Astrophysics Data System (ADS)

    Sato, Aki-Hiro; Nishimura, Maiko; Hołyst, Janusz A.

    2010-07-01

    We study the scaling behavior of quotation activities for various currency pairs in the foreign exchange market. The components’ centrality is estimated from multiple time series and visualized as a currency pair network. The power-law relationship between a mean of quotation activity and its standard deviation for each currency pair is found. The scaling exponent α and the ratio between common and specific fluctuations η increase with the length of the observation time window Δt. The result means that although for Δt=1 (min), the market dynamics are governed by specific processes, and at a longer time scale Δt>100 (min) the common information flow becomes more important. We point out that quotation activities are not independently Poissonian for Δt=1 (min), and temporally or mutually correlated activities of quotations can happen even at this time scale. A stochastic model for the foreign exchange market based on a bipartite graph representation is proposed.

  13. Breathlessness in the Elderly During the Last Year of Life Sufficient to Restrict Activity: Prevalence, Pattern and Associated Factors

    PubMed Central

    Johnson, Miriam J.; Bland, J. Martin; Gahbauer, Evelyne A.; Ekström, Magnus; Sinnarajah, Aynharan; Gill, Thomas M.; Currow, David C.

    2015-01-01

    Objectives Breathlessness is prevalent in older people. Symptom control at the end of life is important. This study investigated relationships between age, clinical characteristics and breathlessness sufficient to have people spend at least one half a day in that month in bed or cut down on their usual activities (restricting breathlessness) during the last year of life. Design Secondary data-analysis Setting General community Participants 754 non-disabled persons, aged 70 and older. Monthly telephone interviews were conducted to determine the occurrence of restricting breathlessness. The primary outcome was the percentage of months with restricting breathlessness reported during the last year of life. Results Data regarding breathlessness were available for 548/589 (93.0%) decedents (mean age 86.7 years (range 71 to 106; males 38.8%). 311/548 (56.8%) reported restricting breathlessness at some time-point during the last year of life but no-one reported this every month. Frequency increased in the months closer to death irrespective of cause. Restricting breathlessness was associated with anxiety, (0.25 percentage point increase in months breathlessness per percentage point months reported anxiety, 95% CI 0.16 to 0.34, P<0.001), depression (0.14, 0.05 to 0.24, P=0.003) and mobility problems (0.07, 0.03 to 0.1, P<0.001). Percentage months of restricting breathlessness increased if chronic lung disease was noted at the most recent comprehensive assessment (6.62 percentage points, 95% CI 4.31 to 8.94, P<0.001), heart failure (3.34, 0.71 to 5.97, P<0.01), and ex-smoker status (3.01, 0.94 to 5.07, P=0.004), but decreased with older age (−0.19, −0.37 to −0.02, P=0.03). Conclusion Restricting breathlessness increased in this elderly population in the months preceding death from any cause. Breathlessness should be assessed and managed in the context of poor prognosis. PMID:26782854

  14. Leptin-sensitive neurons in the arcuate nucleus integrate activity and temperature circadian rhythms and anticipatory responses to food restriction.

    PubMed

    Wiater, Michael F; Li, Ai-Jun; Dinh, Thu T; Jansen, Heiko T; Ritter, Sue

    2013-10-15

    Previously, we investigated the role of neuropeptide Y and leptin-sensitive networks in the mediobasal hypothalamus in sleep and feeding and found profound homeostatic and circadian deficits with an intact suprachiasmatic nucleus. We propose that the arcuate nuclei (Arc) are required for the integration of homeostatic circadian systems, including temperature and activity. We tested this hypothesis using saporin toxin conjugated to leptin (Lep-SAP) injected into Arc in rats. Lep-SAP rats became obese and hyperphagic and progressed through a dynamic phase to a static phase of growth. Circadian rhythms were examined over 49 days during the static phase. Rats were maintained on a 12:12-h light-dark (LD) schedule for 13 days and, thereafter, maintained in continuous dark (DD). After the first 13 days of DD, food was restricted to 4 h/day for 10 days. We found that the activity of Lep-SAP rats was arrhythmic in DD, but that food anticipatory activity was, nevertheless, entrainable to the restricted feeding schedule, and the entrained rhythm persisted during the subsequent 3-day fast in DD. Thus, for activity, the circuitry for the light-entrainable oscillator, but not for the food-entrainable oscillator, was disabled by the Arc lesion. In contrast, temperature remained rhythmic in DD in the Lep-SAP rats and did not entrain to restricted feeding. We conclude that the leptin-sensitive network that includes the Arc is required for entrainment of activity by photic cues and entrainment of temperature by food, but is not required for entrainment of activity by food or temperature by photic cues.

  15. Restrictive cardiomyopathy

    MedlinePlus

    Cardiomyopathy - restrictive; Infiltrative cardiomyopathy; Idiopathic myocardial fibrosis ... In a case of restrictive cardiomyopathy, the heart muscle is of normal size or slightly enlarged. Most of the time, it also pumps normally. However, it does ...

  16. 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)…

  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.

  18. 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.

  19. 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

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

    PubMed

    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

    2014-07-16

    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.

  1. Calorie restriction-induced SIRT6 activation delays aging by suppressing NF-κB signaling

    PubMed Central

    Zhang, Nannan; Li, Zhongchi; Mu, Wei; Li, Liyuan; Liang, Yaru; Lu, Maoyang; Wang, Zhuoran; Qiu, Ying; Wang, Zhao

    2016-01-01

    ABSTRACT Calorie restriction (CR) extends lifespan from yeast to mammals. SIRT6 is a member of the sirtuin family of NAD+-dependent histone deacetylases, which is responsible for mediating the effects of CR. The transcription factor NF-κB, which is involved in inflammation and aging, has been shown to be regulated by SIRT6. Here we describe the crucial role of SIRT6 in aging and inflammation. We show that CR had improved renal insufficiency and enhanced SIRT6 expression after 6-month treatment in aged mice. Culture cells in low glucose (LG) conditions also showed resistance to cell senescence and enhanced SIRT6 expression compared to normal glucose (NG) group, showing beneficial effects of the CR-mimic cultural conditions. Moreover, SIRT6 overexpression is sufficient to delay the replicative senescence of WI38 by attenuating NF-κB signaling, while SIRT6 knockdown results in accelerated cell senescence and overactive NF-κB signaling. These findings confirm the key status of CR and disclose the critical role of SIRT6 on aging and inflammation. PMID:26940461

  2. Intrinsic restriction activity by AID/APOBEC family of enzymes against the mobility of retroelements

    PubMed Central

    Ikeda, Terumasa

    2011-01-01

    A large portion of the mammalian genome is derived from ancient transposable elements. Retroelements, transported by an intracellular copy-and-paste process involving an RNA intermediate (retrotransposition), constitute a majority of these mobile genetic elements. Endogenous retroviruses are LTR-type retroelements accounting for around 8% of human or murine genomic DNA. Non-LTR members are present in extremely high copy numbers; with LINE-1 contributing to nearly 40% of human and murine genomes. These LINE-1 elements modify mammalian genomes not only through insertions, but also by indirect replication of nonautonomous retrotransposons such as SINEs. As expected, cellular machineries of vertebrate's innate immunity have evolved to support a balance between retroelement insertions that cause deleterious gene disruptions and those that confer beneficial genetic diversity. The ability of APOBEC3 cytidine deaminases targeting DNA to restrict a broad number of retroviruses and retro-elements is now well established. More recently, the RNA editing family member APOBEC1, a protein involved in lipid transport, has also been shown to be involved in keeping mobile elements under control. This review discusses current understanding of the mechanism of action of the AID/APOBEC family, and their role in controlling the retrotransposition of endogenous retroelements. PMID:22479686

  3. 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

  4. Multi-scale statistical analysis of coronal solar activity

    DOE PAGES

    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.

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

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... matter, except daily newspapers; or (2) Engage in any sales activity, including the solicitation of... of postage; (ii) Primarily engaged in the business of sending advertising, promotional, or...

  6. 5 CFR 7001.102 - Restrictions on outside employment and business activities.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... matter, except daily newspapers; or (2) Engage in any sales activity, including the solicitation of... of postage; (ii) Primarily engaged in the business of sending advertising, promotional, or...

  7. 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

  8. 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

  9. Prevalence and Stability of Active Play, Restricted Movement and Television Viewing in Infants

    ERIC Educational Resources Information Center

    Hesketh, Kylie D.; Crawford, David A.; Abbott, Gavin; Campbell, Karen J.; Salmon, Jo

    2015-01-01

    This study describes engagement in and stability of physical activity and sedentary behaviours in early life, and assesses associations with sex, maternal education and developmental stage. Maternal-report data at child age 4, 9 and 20 months were collected from 542 families in the Melbourne Infant Feeding Activity and Nutrition Trial Program.…

  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.

  11. 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

  12. 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.

  13. 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.

  14. Secreted Vago restricts West Nile virus infection in Culex mosquito cells by activating the Jak-STAT pathway.

    PubMed

    Paradkar, Prasad N; Trinidad, Lee; Voysey, Rhonda; Duchemin, Jean-Bernard; Walker, Peter J

    2012-11-13

    Although West Nile virus (WNV) and other arthropod-borne viruses are a major public health problem, the mechanisms of antiviral immunity in mosquitoes are poorly understood. Dicer-2, responsible for the RNAi-mediated response through the C-terminal RNase-III domain, also contains an N-terminal DExD/H-box helicase domain similar to mammalian RIG-I/MDA5 which, in Drosophila, was found to be required for activation of an antiviral gene, Vago. Here we show that the Culex orthologue of Vago (CxVago) is up-regulated in response to WNV infection in a Dicer-2-dependent manner. Further, our data show that CxVago is a secreted peptide that restricts WNV infection by activation of the Jak-STAT pathway. Thus, Vago appears to function as an IFN-like antiviral cytokine in mosquitoes.

  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. 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.

  17. 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... activities which are in addition to those that would otherwise be available to the Native American...

  18. 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... activities which are in addition to those that would otherwise be available to the Native American...

  19. 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... activities which are in addition to those that would otherwise be available to the Native American...

  20. 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

  1. The APC/C E3 Ligase Complex Activator FZR1 Restricts BRAF Oncogenic Function.

    PubMed

    Wan, Lixin; Chen, Ming; Cao, Juxiang; Dai, Xiangpeng; Yin, Qing; Zhang, Jinfang; Song, Su-Jung; Lu, Ying; Liu, Jing; Inuzuka, Hiroyuki; Katon, Jesse M; Berry, Kelsey; Fung, Jacqueline; Ng, Christopher; Liu, Pengda; Song, Min Sup; Xue, Lian; Bronson, Roderick T; Kirschner, Marc W; Cui, Rutao; Pandolfi, Pier Paolo; Wei, Wenyi

    2017-02-07

    BRAF drives tumorigenesis by coordinating the activation of RAS/RAF/MEK/ERK oncogenic signaling cascade. However, upstream pathway(s) governing BRAF kinase activity and protein stability remains undefined. Here, we report that in primary cells with active APCFZR1, APCFZR1 earmarks BRAF for ubiquitination-mediated proteolysis, while in cancer cells with APC-free FZR1, FZR1 suppresses BRAF through disrupting BRAF dimerization. Moreover, we identified FZR1 as a direct target of ERK and CYCLIN D1/CDK4 kinases. Phosphorylation of FZR1 inhibits APCFZR1, leading to elevation of a cohort of oncogenic APCFZR1 substrates to facilitate melanomagenesis. Importantly, CDK4 and/or BRAF/MEK inhibitors restore APCFZR1 E3 ligase activity, which might be critical for their clinical effects. Furthermore, FZR1 depletion co-operates with AKT hyper-activation to transform primary melanocytes, while genetic ablation of Fzr1 synergizes with Pten loss, leading to aberrant co-activation of BRAF/ERK and AKT signaling in mice. Our findings therefore reveal a reciprocal suppression mechanism between FZR1 and BRAF in controlling tumorigenesis.

  2. Reference distribution functions for magnetically confined plasmas from the minimum entropy production theorem and the MaxEnt principle, subject to the scale-invariant restrictions

    NASA Astrophysics Data System (ADS)

    Sonnino, Giorgio; Cardinali, Alessandro; Steinbrecher, Gyorgy; Peeters, Philippe; Sonnino, Alberto; Nardone, Pasquale

    2013-12-01

    We derive the expression of the reference distribution function for magnetically confined plasmas far from the thermodynamic equilibrium. The local equilibrium state is fixed by imposing the minimum entropy production theorem and the maximum entropy (MaxEnt) principle, subject to scale invariance restrictions. After a short time, the plasma reaches a state close to the local equilibrium. This state is referred to as the reference state. The aim of this Letter is to determine the reference distribution function (RDF) when the local equilibrium state is defined by the above mentioned principles. We prove that the RDF is the stationary solution of a generic family of stochastic processes corresponding to an universal Landau-type equation with white parametric noise. As an example of application, we consider a simple, fully ionized, magnetically confined plasmas, with auxiliary Ohmic heating. The free parameters are linked to the transport coefficients of the magnetically confined plasmas, by the kinetic theory.

  3. 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,…

  4. Correlation Between Fetal Activity and the Neonatal Behavorial Assessment Scale.

    ERIC Educational Resources Information Center

    Ishikawa, Akashi; Minamide, Etsuko

    1984-01-01

    A total of 14 women recorded fetal movements during one week of their pregnancies, and Brazelton Neonatal Behavorial Assessment Scale exams were performed on the infants during their first week of life. Correlations were computed between fetal activity and neonatal behavior. (Author/RH)

  5. Gastric bypass surgery, but not caloric restriction, decreases dipeptidyl peptidase-4 activity in obese patients with type 2 diabetes

    PubMed Central

    Alam, M. L.; Van der Schueren, B. J.; Ahren, B.; Wang, G. C.; Swerdlow, N. J.; Arias, S.; Bose, M.; Gorroochurn, P.; Teixeira, J.; McGinty, J.; Laferrère, B.

    2013-01-01

    The mechanism by which incretins and their effect on insulin secretion increase markedly following gastric bypass (GBP) surgery is not fully elucidated. We hypothesized that a decrease in the activity of dipeptidyl peptidase-4 (DPP-4), the enzyme which inactivates incretins, may explain the rise in incretin levels post-GBP. Fasting plasma DPP-4 activity was measured after 10-kg equivalent weight loss by GBP (n = 16) or by caloric restriction (CR, n = 14) in obese patients with type 2 diabetes. DPP-4 activity decreased after GBP by 11.6% (p = 0.01), but not after CR. The increased peak glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) response to oral glucose after GBP did not correlate with DPP-4 activity. The decrease in fasting plasma DPP-4 activity after GBP occurred by a mechanism independent of weight loss and did not relate to change in incretin concentrations. Whether the change in DPP-4 activity contributes to improved diabetes control after GBP remains therefore to be determined. PMID:21210936

  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.

  7. 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

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

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... required by the Postal Service for use by its employees or customers; (ii) The transportation of mail under... 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 §...

  10. 20 CFR 668.350 - Are there any restrictions on allowable activities?

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... in the Act. Individuals in OJT must: (1) Be compensated at the same rates, including periodic... in the area in the absence of such funds. (WIA sec. 195(2).) (f) INA grantees must not spend funds on activities that displace currently employed individuals, impair existing contracts for services, or in...

  11. Enhanced Locomotor Activity Is Required to Exert Dietary Restriction-Dependent Increase of Stress Resistance in Drosophila.

    PubMed

    Ghimire, Saurav; Kim, Man Su

    2015-01-01

    Dietary restriction (DR) is known to be one of the most effective interventions to increase stress resistance, yet the mechanisms remain elusive. One of the most obvious DR-induced changes in phenotype is an increase in locomotor activity. Although it is conceptually perceivable that nutritional scarcity should prompt enhanced foraging behavior to garner additional dietary resources, the significance of enhanced movement activity has not been associated with the DR-dependent increase of stress resistance. In this study, we confirmed that flies raised on DR exhibited enhanced locomotive activity and increased stress resistance. Excision of fly wings minimized the DR-induced increase in locomotive activity, which resulted in attenuation of the DR-dependent increase of stress resistance. The possibility that wing clipping counteracts the DR by coercing flies to have more intake was ruled out since it did not induce any weight gain. Rather it was found that elimination of reactive oxygen species (ROS) that is enhanced by DR-induced upregulation of expression of antioxidant genes was significantly reduced by wing clipping. Collectively, our data suggests that DR increased stress resistance by increasing the locomotor activity, which upregulated expression of protective genes including, but not limited to, ROS scavenger system.

  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. 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

  14. Intracellular multiplication of Paracoccidioides brasiliensis in macrophages: killing and restriction of multiplication by activated macrophages.

    PubMed Central

    Brummer, E; Hanson, L H; Restrepo, A; Stevens, D A

    1989-01-01

    The effect of coculturing yeast-form Paracoccidioides brasiliensis with murine cells was studied. Coculture of resident peritoneal or pulmonary macrophages with P. brasiliensis for 72 h dramatically enhanced fungal multiplication 19.3 +/- 2.4- and 4.7 +/- 0.8-fold, respectively, compared with cocultures with lymph node cells or complete tissue culture medium alone. Support of P. brasiliensis multiplication by resident peritoneal macrophages was macrophage dose dependent. Lysates of macrophages, supernatants from macrophage cultures, or McVeigh-Morton broth, like complete tissue culture medium, did not support multiplication of P. brasiliensis in 72-h cultures. Time course microscopic studies of cocultures in slide wells showed that macrophages ingested P. brasiliensis cells and that the ingested cells multiplied intracellularly. In sharp contrast to resident macrophages, lymphokine-activated peritoneal and pulmonary macrophages not only prevented multiplication but reduced inoculum CFU by 96 and 100%, respectively, in 72 h. Microscopic studies confirmed killing and digestion of P. brasiliensis ingested by activated macrophages in 48 h. These findings indicate that resident macrophages are permissive for intracellular multiplication of P. brasiliensis and that this could be a factor in pathogenicity. By contrast, activated macrophages are fungicidal for P. brasiliensis. Images PMID:2744848

  15. CRL4A(CRBN) E3 ubiquitin ligase restricts BK channel activity and prevents epileptogenesis.

    PubMed

    Liu, Jiye; Ye, Jia; Zou, Xiaolong; Xu, Zhenghao; Feng, Yan; Zou, Xianxian; Chen, Zhong; Li, Yuezhou; Cang, Yong

    2014-05-21

    Ion channels regulate membrane excitation, and mutations of ion channels often cause serious neurological disorders including epilepsy. Compared with extensive analyses of channel protein structure and function, much less is known about the fine tuning of channel activity by post-translational modification. Here we report that the large conductance, Ca(2+)- and voltage-activated K(+) (BK) channels are targeted by the E3 ubiquitin ligase CRL4A(CRBN) for polyubiquitination and retained in the endoplasmic reticulum (ER). Inactivation of CRL4A(CRBN) releases deubiquitinated BK channels from the ER to the plasma membrane, leading to markedly enhanced channel activity. Mice with CRL4A(CRBN) mutation in the brain or treated with a CRL4A(CRBN) inhibitor are very sensitive to seizure induction, which can be attenuated by blocking BK channels. Finally, the mutant mice develop spontaneous epilepsy when aged. Therefore, ubiquitination of BK channels before their cell surface expression is an important step to prevent systemic neuronal excitability and epileptogenesis.

  16. 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

  17. A restricted parabrachial pontine region is active during non-rapid eye movement sleep.

    PubMed

    Torterolo, P; Sampogna, S; Chase, M H

    2011-09-08

    The principal site that generates both rapid eye movement (REM) sleep and wakefulness is located in the mesopontine reticular formation, whereas non-rapid eye movement (NREM) sleep 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 parabrachial region (CLPB). The number of Fos+ neurons in the CLPB during NREM was significantly greater (67.9±10.9, P<0.0001) compared with 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

  18. 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.

  19. 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

  20. Species-Specific Activity of SIV Nef and HIV-1 Vpu in Overcoming Restriction by Tetherin/BST2

    PubMed Central

    Neidermyer, William; Rahmberg, Andrew; Mackey, John; Fofana, Ismael Ben; Johnson, Welkin E.; Westmoreland, Susan; Evans, David T.

    2009-01-01

    Tetherin, also known as BST2, CD317 or HM1.24, was recently identified as an interferon-inducible host–cell factor that interferes with the detachment of virus particles from infected cells. HIV-1 overcomes this restriction by expressing an accessory protein, Vpu, which counteracts tetherin. Since lentiviruses of the SIVsmm/mac/HIV-2 lineage do not have a vpu gene, this activity has likely been assumed by other viral gene products. We found that deletion of the SIVmac239 nef gene significantly impaired virus release in cells expressing rhesus macaque tetherin. Virus release could be restored by expressing Nef in trans. However, Nef was unable to facilitate virus release in the presence of human tetherin. Conversely, Vpu enhanced virus release in the presence of human tetherin, but not in the presence of rhesus tetherin. In accordance with the species-specificity of Nef in mediating virus release, SIV Nef downregulated cell-surface expression of rhesus tetherin, but did not downregulate human tetherin. The specificity of SIV Nef for rhesus tetherin mapped to four amino acids in the cytoplasmic domain of the molecule that are missing from human tetherin, whereas the specificity of Vpu for human tetherin mapped to amino acid differences in the transmembrane domain. Nef alleles of SIVsmm, HIV-2 and HIV-1 were also able to rescue virus release in the presence of both rhesus macaque and sooty mangabey tetherin, but were generally ineffective against human tetherin. Thus, the ability of Nef to antagonize tetherin from these Old World primates appears to be conserved among the primate lentiviruses. These results identify Nef as the viral gene product of SIV that opposes restriction by tetherin in rhesus macaques and sooty mangabeys, and reveal species-specificity in the activities of both Nef and Vpu in overcoming tetherin in their respective hosts. PMID:19436700

  1. Impairments, activity limitations and participation restrictions experienced in the first year following a critical illness: protocol for a systematic review

    PubMed Central

    Coffey Scott, Jacqueline; Hinman, Rana S; Lee, Alan Chong; Smith, James M

    2017-01-01

    Introduction Critical illness requiring intensive care unit (ICU) management is a life-altering event with ∼25% of ICU survivors experiencing persistent reductions in physical functioning, impairments in mental health, cognitive dysfunction and decreased quality of life. This constellation of problems is known as ‘postintensive care syndrome’ (PICS) and may persist for months and/or years. The purpose of this systematic review is to identify the scope and magnitude of physical problems associated with PICS during the first year after discharge from ICU, using the International Classification of Functioning, Disability and Health framework to elucidate the impairments of body functions and structures, activity limitations and participation restrictions. Methods and analysis Medline (Ovid), Cochrane Database of Systematic Reviews (Ovid), Cochrane Central Register of Controlled Trials (Ovid), PubMed, CINAHL (EBSCO), Web of Science and EMBASE will be systematically searched for observational studies reporting the physical impairments of body functions and structures, activity limitations and participation restrictions associated with PICS. Two reviewers will assess the articles for eligibility according to prespecified selection criteria, after which an independent reviewer will perform data extraction which will be validated by a second independent reviewer. Quality appraisal will be performed by two independent reviewers. Outcomes of the included studies will be summarised in tables and in narrative format and meta-analyses will be conducted where appropriate. Ethics and dissemination Formal ethical approval is not required as no primary data is collected. This systematic review will identify the scope and magnitude of physical problems associated with PICS during the first year after discharge from ICU and will be disseminated through a peer-reviewed publication and at conference meetings, to inform practice and future research on the physical problems

  2. TAP, a novel T cell-activating protein involved in the stimulation of MHC-restricted T lymphocytes

    PubMed Central

    1986-01-01

    Five mAbs have been generated and used to characterize TAP (T cell activating protein) a novel, functional murine T cell membrane antigen. The TAP molecule is a 12-kD protein that is synthesized by T cells. By antibody crossblocking, it appears to be closely associated with a 16- kD protein on the T cell membrane also identified with a novel mAb. These molecules are clearly distinct from the major well-characterized murine T cell antigens previously described. Antibody binding to TAP can result in the activation of MHC-restricted, antigen-specific inducer T cell hybridomas that is equivalent in magnitude to maximal antigen or lectin stimulation. This is a direct effect of soluble antibody and does not require accessory cells or other factors. The activating anti-TAP mAbs are also mitogenic for normal heterogeneous T lymphocytes in the presence of accessory cells or IL-1. In addition, these antibodies are observed to modulate specific immune stimulation. Thus, the activating anti-TAP mAbs synergise with antigen-specific stimulation of T cells, while a nonactivating anti-TAP mAb inhibits antigen driven activation. These observations suggest that the TAP molecule may participate in physiologic T cell activation. The possible relationship of TAP to known physiologic triggering structures, the T3- T cell receptor complex, is considered. TAP is expressed on 70% of peripheral T cells and therefore defines a major T cell subset, making it perhaps the first example of a murine subset-specific activating protein. PMID:2418146

  3. 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

  4. 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

  5. Effects of potassium chloride on plasma renin activity during sodium restriction in normal man.

    PubMed

    Bauer, J H; Gauntner, W C; Nolph, K D; Van Stone, J C

    1977-08-01

    Previous studies have suggested that large intakes of potassium (K) will suppress plasma renin activity (PRA) in normal man. The effect of more modest intakes of K on PRA is unclear. The present study was designed to compare the PRA in 11 normal volunteers maintained on an electrolyte-free diet (7000 J), with and without the addition of 50 mEq/day of potassium chloride (7000 J + KCl), well within the limits of usual dietary consumption. Control recumbent and 2 hr of upright PRA determinations were made by radioimmunoassay prior to the initiation of either the 7000 J diet or the 7000 J + KCl diet and on the fourth day of the diet, at a time when urinary sodium, K, and chloride excretions were near intakes. Mean (+/- S.E.M.) PRA's are indicated in Table II. There are significant (p less than 0.01) differences between (1) all respective recumbent and upright posture positions and (2) before and after the administration of 7000 J and 7000 J + KCl. However, there are no significant differences between (1) control periods or (2) before and after the addition of KCl to the electrolyte-free diet. We conclude from these studies that K, given in modest amounts, has no inhibiting effect on PRA.

  6. Ephrin-mediated restriction of ERK1/2 activity delimits the number of pigment cells in the Ciona CNS

    PubMed Central

    Haupaix, Nicolas; Abitua, Philip B.; Sirour, Cathy; Yasuo, Hitoyoshi; Levine, Michael; Hudson, Clare

    2014-01-01

    Recent evidence suggests that ascidian pigment cells are related to neural crest-derived melanocytes of vertebrates. Using live-imaging, we determine a revised cell lineage of the pigment cells in Ciona intestinalis embryos. The neural precursors undergo successive rounds of anterior-posterior (A-P) oriented cell divisions, starting at the blastula 64-cell stage. A previously unrecognized fourth A-P oriented cell division in the pigment cell lineage leads to the generation of the post-mitotic pigment cell precursors. We provide evidence that MEK/ERK signals are required for pigment cell specification until approximately 30 minutes after the final cell division has taken place. Following each of the four A-P oriented cell divisions, ERK1/2 is differentially activated in the posterior sister cells, into which the pigment cell lineage segregates. Eph/ephrin signals are critical during the third A-P oriented cell division to spatially restrict ERK1/2 activation to the posterior daughter cell. Targeted inhibition of Eph/ephrin signals results in, at neurula stages, anterior expansion of both ERK1/2 activation and a pigment cell lineage marker and subsequently, at larval stages, supernumerary pigment cells. We discuss the implications of these findings with respect to the evolution of the vertebrate neural crest. PMID:25062608

  7. A dietary regimen of caloric restriction or pharmacological activation of SIRT1 to delay the onset of neurodegeneration

    PubMed Central

    Gräff, Johannes; Kahn, Martin; Samiei, Alireza; Gao, Jun; Ota, Kristie T.; Rei, Damien; Tsai, Li-Huei

    2013-01-01

    Caloric restriction (CR) is a dietary regimen known to promote lifespan by slowing down the occurrence of age-dependent diseases. The greatest risk factor for neurodegeneration in the brain is age, from which follows that CR might also attenuate the progressive loss of neurons that is often associated with impaired cognitive capacities. In this study, we used a transgenic mouse model that allows for a temporally and spatially controlled onset of neurodegeneration to test the potentially beneficial effects of CR. We found that in this model, CR significantly delayed the onset of neurodegeneration, synaptic loss and dysfunction, and thereby preserved cognitive capacities. Mechanistically, CR induced the expression of the known lifespan-regulating protein SIRT1, prompting us to test whether a pharmacological activation of SIRT1 might recapitulate CR. We found that oral administration of a SIRT1-activating compound essentially replicated the beneficial effects of CR. Thus, SIRT1-activating compounds might provide a pharmacological alternative to the regimen of CR against neurodegeneration and its associated ailments. PMID:23699506

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

    PubMed Central

    Wang, Haiyan; Arias, Edward B.

    2016-01-01

    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 Thr309 and Ser474 along with greater Akt2 activity, 3) concomitant with enhanced phosphorylation of several Akt substrates, including an Akt substrate of 160 kDa on Thr642 and Ser588, filamin C on Ser2213 and proline-rich Akt substrate of 40 kDa on Thr246, but not TBC1D1 on Thr596; 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

  9. Ephrin-mediated restriction of ERK1/2 activity delimits the number of pigment cells in the Ciona CNS.

    PubMed

    Haupaix, Nicolas; Abitua, Philip B; Sirour, Cathy; Yasuo, Hitoyoshi; Levine, Michael; Hudson, Clare

    2014-10-01

    Recent evidence suggests that ascidian pigment cells are related to neural crest-derived melanocytes of vertebrates. Using live-imaging, we determine a revised cell lineage of the pigment cells in Ciona intestinalis embryos. The neural precursors undergo successive rounds of anterior-posterior (A-P) oriented cell divisions, starting at the blastula 64-cell stage. A previously unrecognized fourth A-P oriented cell division in the pigment cell lineage leads to the generation of the post-mitotic pigment cell precursors. We provide evidence that MEK/ERK signals are required for pigment cell specification until approximately 30min after the final cell division has taken place. Following each of the four A-P oriented cell divisions, ERK1/2 is differentially activated in the posterior sister cells, into which the pigment cell lineage segregates. Eph/ephrin signals are critical during the third A-P oriented cell division to spatially restrict ERK1/2 activation to the posterior daughter cell. Targeted inhibition of Eph/ephrin signals results in, at neurula stages, anterior expansion of both ERK1/2 activation and a pigment cell lineage marker and subsequently, at larval stages, supernumerary pigment cells. We discuss the implications of these findings with respect to the evolution of the vertebrate neural crest.

  10. 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.

  11. Caloric Restriction Is More Efficient than Physical Exercise to Protect from Cisplatin Nephrotoxicity via PPAR-Alpha Activation.

    PubMed

    Estrela, Gabriel R; Wasinski, Frederick; Batista, Rogério O; Hiyane, Meire I; Felizardo, Raphael J F; Cunha, Flavia; de Almeida, Danilo C; Malheiros, Denise M A C; Câmara, Niels O S; Barros, Carlos C; Bader, Michael; Araujo, Ronaldo C

    2017-01-01

    The antineoplastic drug cisplatin promotes renal injury, which limits its use. Protocols that reduce renal cisplatin toxicity will allow higher doses to be used in cisplatin treatment. Here, we compare physical exercise and caloric restriction (CR) as protocols to reduce cisplatin renal injury in mice. Male C57BL/6 were divided into four groups: Control, cisplatin, exercise + cisplatin, and 30% CR + cisplatin. Animals were injected with a single dose of cisplatin (20 mg/kg i.p.) and sacrificed 96 h after injection. Quantitative real time PCR, histological analyses, immunohistochemistry, and biochemical measurements were performed to investigate renal injury, necrosis, apoptosis, and inflammatory mechanisms. Both protocols protected against cisplatin renal injury, but CR was more effective in reducing uraemia and renal necrosis. The CR + Cisplatin group exhibited reduced serum IL-1β and TNF-α levels. No differences were noted in the renal mRNA expression of cytokines. Both interventions reduced apoptosis, but only the CR + Cisplatin group decreased TNFR2 protein expression. PPAR-α was activated in mice after CR. An antagonist of PPAR-α blocked the protective effect of CR. Both interventions attenuated the nephrotoxicity caused by cisplatin injection, but CR + Cisplatin showed a better response by modulating TNFR2. Moreover, part of the CR benefit depends on PPAR-α activation.

  12. Caloric Restriction Is More Efficient than Physical Exercise to Protect from Cisplatin Nephrotoxicity via PPAR-Alpha Activation

    PubMed Central

    Estrela, Gabriel R.; Wasinski, Frederick; Batista, Rogério O.; Hiyane, Meire I.; Felizardo, Raphael J. F.; Cunha, Flavia; de Almeida, Danilo C.; Malheiros, Denise M. A. C.; Câmara, Niels O. S.; Barros, Carlos C.; Bader, Michael; Araujo, Ronaldo C.

    2017-01-01

    The antineoplastic drug cisplatin promotes renal injury, which limits its use. Protocols that reduce renal cisplatin toxicity will allow higher doses to be used in cisplatin treatment. Here, we compare physical exercise and caloric restriction (CR) as protocols to reduce cisplatin renal injury in mice. Male C57BL/6 were divided into four groups: Control, cisplatin, exercise + cisplatin, and 30% CR + cisplatin. Animals were injected with a single dose of cisplatin (20 mg/kg i.p.) and sacrificed 96 h after injection. Quantitative real time PCR, histological analyses, immunohistochemistry, and biochemical measurements were performed to investigate renal injury, necrosis, apoptosis, and inflammatory mechanisms. Both protocols protected against cisplatin renal injury, but CR was more effective in reducing uraemia and renal necrosis. The CR + Cisplatin group exhibited reduced serum IL-1β and TNF-α levels. No differences were noted in the renal mRNA expression of cytokines. Both interventions reduced apoptosis, but only the CR + Cisplatin group decreased TNFR2 protein expression. PPAR-α was activated in mice after CR. An antagonist of PPAR-α blocked the protective effect of CR. Both interventions attenuated the nephrotoxicity caused by cisplatin injection, but CR + Cisplatin showed a better response by modulating TNFR2. Moreover, part of the CR benefit depends on PPAR-α activation. PMID:28303105

  13. Distinct activation phenotype of a highly conserved novel HLA-B57-restricted epitope during dengue virus infection

    PubMed Central

    Townsley, Elizabeth; Woda, Marcia; Thomas, Stephen J; Kalayanarooj, Siripen; Gibbons, Robert V; Nisalak, Ananda; Srikiatkhachorn, Anon; Green, Sharone; Stephens, Henry AF; Rothman, Alan L; Mathew, Anuja

    2014-01-01

    Variation in the sequence of T-cell epitopes between dengue virus (DENV) serotypes is believed to alter memory T-cell responses during second heterologous infections. We identified a highly conserved, novel, HLA-B57-restricted epitope on the DENV NS1 protein. We predicted higher frequencies of B57-NS126–34-specific CD8+ T cells in peripheral blood mononuclear cells from individuals undergoing secondary rather than primary DENV infection. However, high tetramer-positive T-cell frequencies during acute infection were seen in only one of nine subjects with secondary infection. B57-NS126–34-specific and other DENV epitope-specific CD8+ T cells, as well as total CD8+ T cells, expressed an activated phenotype (CD69+ and/or CD38+) during acute infection. In contrast, expression of CD71 was largely limited to DENV epitope-specific CD8+ T cells. In vitro stimulation of cell lines indicated that CD71 expression was differentially sensitive to stimulation by homologous and heterologous variant peptides. CD71 may represent a useful marker of antigen-specific T-cell activation. PMID:23941420

  14. Cell type-restricted activity of hnRNPM promotes breast cancer metastasis via regulating alternative splicing.

    PubMed

    Xu, Yilin; Gao, Xin D; Lee, Jae-Hyung; Huang, Huilin; Tan, Haiyan; Ahn, Jaegyoon; Reinke, Lauren M; Peter, Marcus E; Feng, Yue; Gius, David; Siziopikou, Kalliopi P; Peng, Junmin; Xiao, Xinshu; Cheng, Chonghui

    2014-06-01

    Tumor metastasis remains the major cause of cancer-related death, but its molecular basis is still not well understood. Here we uncovered a splicing-mediated pathway that is essential for breast cancer metastasis. We show that the RNA-binding protein heterogeneous nuclear ribonucleoprotein M (hnRNPM) promotes breast cancer metastasis by activating the switch of alternative splicing that occurs during epithelial-mesenchymal transition (EMT). Genome-wide deep sequencing analysis suggests that hnRNPM potentiates TGFβ signaling and identifies CD44 as a key downstream target of hnRNPM. hnRNPM ablation prevents TGFβ-induced EMT and inhibits breast cancer metastasis in mice, whereas enforced expression of the specific CD44 standard (CD44s) splice isoform overrides the loss of hnRNPM and permits EMT and metastasis. Mechanistically, we demonstrate that the ubiquitously expressed hnRNPM acts in a mesenchymal-specific manner to precisely control CD44 splice isoform switching during EMT. This restricted cell-type activity of hnRNPM is achieved by competition with ESRP1, an epithelial splicing regulator that binds to the same cis-regulatory RNA elements as hnRNPM and is repressed during EMT. Importantly, hnRNPM is associated with aggressive breast cancer and correlates with increased CD44s in patient specimens. These findings demonstrate a novel molecular mechanism through which tumor metastasis is endowed by the hnRNPM-mediated splicing program.

  15. 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

  16. Assessment of Fetal Autonomic Nervous System Activity by Fetal Magnetocardiography: Comparison of Normal Pregnancy and Intrauterine Growth Restriction

    PubMed Central

    Fukushima, Akimune; Nakai, Kenji; Kanasugi, Tomonobu; Terata, Miyuki; Sugiyama, Toru

    2011-01-01

    Objective. To clarify the developmental activity of the autonomic nervous system (ANS) of the normal fetus and intrauterine growth restriction (IUGR) cases using fetal magnetocardiography (FMCG). Subjects and Methods. Normal pregnancy (n = 35) and IUGR (n = 12) cases at 28–39 and 32–37 weeks of gestation, respectively, were included in this study. The R-R interval variability was used to calculate the coefficient of variance (CVRR) and low frequency/high frequency (LF/HF) ratio. Results. The value of CVRR in the normal pregnancy group displayed a slight increasing trend with gestational age. However, no such trend was observed in the IUGR group. In contrast, the LF/HF ratio in both the normal pregnancy group and the IUGR group clearly increased over the gestational period; the normal group showing statistical significance. Conclusion. The development of fetal ANS activity in IUGR cases might differ from that observed in the normal pregnancy group, and this may facilitate early detection of IUGR. PMID:21547087

  17. 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.

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

    PubMed

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

    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(5)) model systems with well-known electronic structure, viz., atomic Fe(3+), high-spin [FeCl6](3-) with ligand donor bonding, and low-spin [Fe(CN)6](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.

  19. Distinct activation phenotype of a highly conserved novel HLA-B57-restricted epitope during dengue virus infection.

    PubMed

    Townsley, Elizabeth; Woda, Marcia; Thomas, Stephen J; Kalayanarooj, Siripen; Gibbons, Robert V; Nisalak, Ananda; Srikiatkhachorn, Anon; Green, Sharone; Stephens, Henry A F; Rothman, Alan L; Mathew, Anuja

    2014-01-01

    Variation in the sequence of T-cell epitopes between dengue virus (DENV) serotypes is believed to alter memory T-cell responses during second heterologous infections. We identified a highly conserved, novel, HLA-B57-restricted epitope on the DENV NS1 protein. We predicted higher frequencies of B57-NS1(26-34) -specific CD8(+) T cells in peripheral blood mononuclear cells from individuals undergoing secondary rather than primary DENV infection. However, high tetramer-positive T-cell frequencies during acute infection were seen in only one of nine subjects with secondary infection. B57-NS1(26-34) -specific and other DENV epitope-specific CD8(+) T cells, as well as total CD8(+) T cells, expressed an activated phenotype (CD69(+) and/or CD38(+)) during acute infection. In contrast, expression of CD71 was largely limited to DENV epitope-specific CD8(+) T cells. In vitro stimulation of cell lines indicated that CD71 expression was differentially sensitive to stimulation by homologous and heterologous variant peptides. CD71 may represent a useful marker of antigen-specific T-cell activation.

  20. Long-range scaling behaviours of human colonic pressure activities

    NASA Astrophysics Data System (ADS)

    Yan, Rongguo; Yan, Guozheng; Zhang, Wenqiang; Wang, Long

    2008-11-01

    The long-range scaling behaviours of human colonic pressure activities under normal physiological conditions are studied by using the method of detrended fluctuation analysis (DFA). The DFA is an effective period representation with a single quantitative scaling exponent α to accurately quantify long-range correlations naturally presented in a complex non-stationary time series. The method shows that the colonic activities of the healthy subjects exhibit long-range power-law correlations; however such correlations either will be destroyed if we randomly shuffle the original data or will cease to be of a power-law form if we chop some high-amplitude spikes off. These facts indicate that the colonic tissue or enteric nervous system (ENS) with a good functional motility has a good memory to its past behaviours and generates well-organized colonic spikes; however such good memory becomes too long to be remembered for the colonic activity of the slow transit constipation (STC) patient and colonic dysmotility occurs.

  1. Let’s Not Waste Time: Using Temporal Information in Clustered Activity Estimation with Spatial Adjacency Restrictions (CAESAR) for Parcellating FMRI Data

    PubMed Central

    Jylänki, Pasi; van Gerven, Marcel A. J.

    2016-01-01

    We have proposed a Bayesian approach for functional parcellation of whole-brain FMRI measurements which we call Clustered Activity Estimation with Spatial Adjacency Restrictions (CAESAR). We use distance-dependent Chinese restaurant processes (dd-CRPs) to define a flexible prior which partitions the voxel measurements into clusters whose number and shapes are unknown a priori. With dd-CRPs we can conveniently implement spatial constraints to ensure that our parcellations remain spatially contiguous and thereby physiologically meaningful. In the present work, we extend CAESAR by using Gaussian process (GP) priors to model the temporally smooth haemodynamic signals that give rise to the measured FMRI data. A challenge for GP inference in our setting is the cubic scaling with respect to the number of time points, which can become computationally prohibitive with FMRI measurements, potentially consisting of long time series. As a solution we describe an efficient implementation that is practically as fast as the corresponding time-independent non-GP model with typically-sized FMRI data sets. We also employ a population Monte-Carlo algorithm that can significantly speed up convergence compared to traditional single-chain methods. First we illustrate the benefits of CAESAR and the GP priors with simulated experiments. Next, we demonstrate our approach by parcellating resting state FMRI data measured from twenty participants as taken from the Human Connectome Project data repository. Results show that CAESAR affords highly robust and scalable whole-brain clustering of FMRI timecourses. PMID:27935937

  2. 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

  3. Differential regulation of parvocellular neuronal activity in the paraventricular nucleus of the hypothalamus following single vs. repeated episodes of water restriction-induced drinking.

    PubMed

    Arnhold, Michelle M; Wotus, Cheryl; Engeland, William C

    2007-07-01

    Acute activation of the hypothalamic-pituitary-adrenal (HPA) axis releases glucocorticoids to maintain homeostasis, whereas prolonged exposure to elevated glucocorticoids has deleterious effects. Due to the potential benefits of limiting stress-induced glucocorticoid secretion, the present study uses drinking in dehydrated rats as a model to delineate mechanisms mobilized to rapidly inhibit HPA activity during stress. Using Fos expression as an indicator of neuronal activation, the effect of a single or repeated episode of dehydration-induced drinking on the activity of magnocellular and parvocellular neurons in the paraventricular nucleus (PVN) of the hypothalamus was examined. Adult male rats underwent a single episode or repeated (six) episodes of water restriction and were sacrificed before or after drinking water in the AM. Plasma osmolality, vasopressin (AVP), adrenocorticotropic hormone (ACTH) and corticosterone were elevated by water restriction and reduced after drinking in both models. Fos expression was elevated in AVP-positive magnocellular PVN neurons and AVP- and corticotropin releasing hormone (CRH)-positive parvocellular PVN neurons after water restriction. Fos expression was reduced in magnocellular AVP neurons after both models of restriction-induced drinking. In contrast, Fos expression did not change in AVP and CRH parvocellular neurons after a single episode of restriction-induced drinking, but was reduced after repeated episodes of restriction-induced drinking. These data indicate that drinking-induced decreases in glucocorticoids in dehydrated rats involve multiple factors including reduction in magnocellular release of vasopressin and reduction in parvocellular neuronal activity. The differential inhibition of PVN parvocellular neurons after repeated rehydration may reflect a conditioned response to repeated stress reduction.

  4. Large-scale multielectrode recording and stimulation of neural activity

    NASA Astrophysics Data System (ADS)

    Sher, A.; Chichilnisky, E. J.; Dabrowski, W.; Grillo, A. A.; Grivich, M.; Gunning, D.; Hottowy, P.; Kachiguine, S.; Litke, A. M.; Mathieson, K.; Petrusca, D.

    2007-09-01

    Large circuits of neurons are employed by the brain to encode and process information. How this encoding and processing is carried out is one of the central questions in neuroscience. Since individual neurons communicate with each other through electrical signals (action potentials), the recording of neural activity with arrays of extracellular electrodes is uniquely suited for the investigation of this question. Such recordings provide the combination of the best spatial (individual neurons) and temporal (individual action-potentials) resolutions compared to other large-scale imaging methods. Electrical stimulation of neural activity in turn has two very important applications: it enhances our understanding of neural circuits by allowing active interactions with them, and it is a basis for a large variety of neural prosthetic devices. Until recently, the state-of-the-art in neural activity recording systems consisted of several dozen electrodes with inter-electrode spacing ranging from tens to hundreds of microns. Using silicon microstrip detector expertise acquired in the field of high-energy physics, we created a unique neural activity readout and stimulation framework that consists of high-density electrode arrays, multi-channel custom-designed integrated circuits, a data acquisition system, and data-processing software. Using this framework we developed a number of neural readout and stimulation systems: (1) a 512-electrode system for recording the simultaneous activity of as many as hundreds of neurons, (2) a 61-electrode system for electrical stimulation and readout of neural activity in retinas and brain-tissue slices, and (3) a system with telemetry capabilities for recording neural activity in the intact brain of awake, naturally behaving animals. We will report on these systems, their various applications to the field of neurobiology, and novel scientific results obtained with some of them. We will also outline future directions.

  5. Restrictive cardiomyopathies.

    PubMed

    Nihoyannopoulos, Petros; Dawson, David

    2009-12-01

    Restrictive cardiomyopathies constitute a heterogenous group of heart muscle conditions that all have, in common, the symptoms of heart failure. Diastolic dysfunction with preserved systolic function is often the only echocardiographic abnormality that may be noted, although systolic dysfunction may also be an integral part of some specific pathologies, particularly in the most advanced cases such as amyloid infiltration of the heart. By far, the majority of restrictive cardiomyopathies are secondary to a systemic disorder such as amyloidosis, sarcoidosis, scleroderma, haemochromatosis, eosinophilic heart disease, or as a result of radiation treatment. The much more rare diagnosis of idiopathic restrictive cardiomyopathy is supported only by the absence of specific pathology on either endomyocardial biopsies or at post-mortem. Restrictive cardiomyopathy is diagnosed based on medical history, physical examination, and tests: such as blood tests, electrocardiogram, chest X-ray, echocardiography, and magnetic resonance imaging. With its wide availability, echocardiography is probably the most important investigation to identify the left ventricular dysfunction and should be performed early and by groups that are familiar with the wide variety of aetiologies. Finally, on rare occasions, the differential diagnosis from constrictive pericarditis may be necessary.

  6. Relationships between persistent large-scale flow anomalies and variation in synoptic-scale eddy activity and cyclogenesis

    NASA Technical Reports Server (NTRS)

    Dole, Randall M.; Neilley, Peter P.

    1988-01-01

    Observational analyses to study the relationships between large-scale flow anomalies and variations in synoptic-scale eddy activity and cyclogenesis are presented. The way in which changes in the large-scale flow influence the behavior of synoptic-scale eddies and the way in which changes in eddies may feedback to influence the large-scale flow anomalies are examined. Situations characterized by differing large-scale flows are compared, showing well-defined diferences in synoptic-scale eddy activity. The net forcings of anomalous mean flows by eddies as deduced from tendency methods and E-vector analyses suggest that synoptic-scale eddies may play an important role in maintaining certain anomalous flow patterns such as blocking.

  7. 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

  8. Short-term dietary energy restriction reduces lean body mass but not performance in physically active men and women.

    PubMed

    Zachwieja, J J; Ezell, D M; Cline, A D; Ricketts, J C; Vicknair, P C; Schorle, S M; Ryan, D H

    2001-05-01

    We studied the effect of moderate, short-term energy restriction on physical performance in physically fit men (n = 13) and women (n = 11) in a controlled clinical research setting with a metabolic kitchen, exercise testing laboratory and training facility. The experiment consisted of a 10 d baseline period followed by either 2 wk of dietary energy restriction (750 kcal/d; n = 16) or energy balance (control; n = 8). During this 24 day study, exercise energy expenditure averaged 465 +/- 5.7 kcal/d in all subjects and was accomplished through treadmill running at a self-selected pace. Body weight was maintained in the control group (-0.36 +/- 0.24kg), but energy restriction resulted in weight loss of -1.29 +/- 0.16 kg (p < 0.001). There was a trend for lean body mass to decline more in the energy restriction group (p = 0.093), accounting for 61% of the weight loss, and urinary nitrogen excretion also tended to be higher in the energy restriction vs. control group (i.e., 13.2 +/- 1.1 vs. 11.2 +/- 1.0g/d; p = 0.089). Muscle strength (leg & shoulder press; 1 repetition maximum) was maintained or increased during the energy restriction period. Muscle endurance, assessed by leg squats to fatigue, and 5 mile run time improved following two weeks of energy restriction or balance. Anaerobic capacity (Wingate Test) increased slightly in the restriction (+ 368 +/- 219 joules) but declined in the control group 649 +/- 288 joules; p<0.05). We conclude that short-term (2 weeks) moderate energy restriction (approximately 750 kcal/d) results in weight loss but does not impair performance in physically fit young men and women.

  9. 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 Physiol 308: H894-H903, 2015). However, the exact mechanism by which Sirt1 in cardiomyocytes mediates the cardioprotective effect of CR remains undetermined. We subjected cardiomyocyte-specific Sirt1 knockout (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 conventional C3 knockout (C3(-/-)) mice treated with CR was similar to that in the ad libitum-fed C3(-/-)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

  10. Mutagenesis of the redox-active disulfide in mercuric ion reductase: Catalysis by mutant enzymes restricted to flavin redox chemistry

    SciTech Connect

    Distefano, M.D.; Au, K.G.; Walsh, C.T. )

    1989-02-07

    Mercuric reductase, a flavoenzyme that possesses a redox-active cystine, Cys{sub 135}Cys{sub 140}, catalyzes the reduction of Hg(II) to Hg(0) by NADPH. As a probe of mechanism, the authors have constructed mutants lacking a redox-active disulfide by eliminating Cys{sub 135} (Ala{sub 135}Cys{sub 140}), Cys{sub 14} (Cys{sub 135}Ala{sub 140}), or both (Ala{sub 135}Ala{sub 140}). Additionally, they have made double mutants that lack Cys{sub 135} (Ala{sub 135}Cys{sub 139}Cys{sub 140}) or Cys{sub 140} (Cys{sub 135}Cys{sub 139}Ala{sub 140}) but introduce a new Cys in place of Gly{sub 139} with the aim of constructing dithiol pairs in the active site that do not form a redox-active disulfide. The resulting mutant enzymes all lack redox-active disulfides and are hence restricted to FAD/FADH{sub 2} redox chemistry. Each mutant enzyme possesses unique physical and spectroscopic properties that reflect subtle differences in the FAD microenvironment. Preliminary evidence for the Ala{sub 135}Cys{sub 139}Cys{sub 14} mutant enzyme suggests that this protein forms a disulfide between the two adjacent Cys residues. Hg(II) titration experiments that correlate the extent of charge-transfer quenching with Hg(II) binding indicate that the Ala{sub 135}Cys{sub 140} protein binds Hg(II) with substantially less avidity than does the wild-type enzyme. All mutant mercuric reductases catalyze transhydrogenation and oxygen reduction reactions through obligatory reduced flavin intermediates at rates comparable to or greater than that of the wild-type enzyme. In multiple-turnover assays which monitored the production of Hg(0), two of the mutant enzymes were observed to proceed through at least 30 turnovers at rates ca. 1000-fold slower than that of wild-type mercuric reductase. They conclude that the Cys{sub 135} and Cys{sub 140} thiols serve as Hg(II) ligands that orient the Hg(II) for subsequent reduction by a reduced flavin intermediate.

  11. Mapping brain activity at scale with cluster computing.

    PubMed

    Freeman, Jeremy; Vladimirov, Nikita; Kawashima, Takashi; Mu, Yu; Sofroniew, Nicholas J; Bennett, Davis V; Rosen, Joshua; Yang, Chao-Tsung; Looger, Loren L; Ahrens, Misha B

    2014-09-01

    Understanding brain function requires monitoring and interpreting the activity of large networks of neurons during behavior. Advances in recording technology are greatly increasing the size and complexity of neural data. Analyzing such data will pose a fundamental bottleneck for neuroscience. We present a library of analytical tools called Thunder built on the open-source Apache Spark platform for large-scale distributed computing. The library implements a variety of univariate and multivariate analyses with a modular, extendable structure well-suited to interactive exploration and analysis development. We demonstrate how these analyses find structure in large-scale neural data, including whole-brain light-sheet imaging data from fictively behaving larval zebrafish, and two-photon imaging data from behaving mouse. The analyses relate neuronal responses to sensory input and behavior, run in minutes or less and can be used on a private cluster or in the cloud. Our open-source framework thus holds promise for turning brain activity mapping efforts into biological insights.

  12. Comparative analysis of anti-restriction activities of ArdA (ColIb-P9) and Ocr (T7) proteins.

    PubMed

    Zavilgelsky, G B; Kotova, V Yu; Rastorguev, S M

    2008-08-01

    Anti-restriction proteins ArdA and Ocr are specific inhibitors of type I restriction-modification enzymes. The IncI1 transmissible plasmid ColIb-P9 ardA and bacteriophage T7 0.3(ocr) genes were cloned in pUC18 vector. Both ArdA (ColIb-P9) and Ocr (T7) proteins inhibit both restriction and modification activities of the type I restriction-modification enzyme (EcoKI) in Escherichia coli K12 cells. ColIb-P9 ardA, T7 0.3(ocr), and the Photorhabdus luminescens luxCDABE genes were cloned in pZ-series vectors with the P(ltetO-1) promoter, which is tightly repressible by the TetR repressor. Controlling the expression of the lux-genes encoding bacterial luciferase demonstrates that the P(ltetO-1) promoter can be regulated over an up to 5000-fold range by supplying anhydrotetracycline to the E. coli MG1655Z1 tetR(+) cells. Effectiveness of the anti-restriction activity of the ArdA and Ocr proteins depended on the intracellular concentration. It is shown that the dissociation constants K(d) for ArdA and Ocr proteins with EcoKI enzyme differ 1700-fold: K(d) (Ocr) = 10(-10) M, K(d) (ArdA) = 1.7.10(-7) M.

  13. 45 CFR 2550.90 - Are there any restrictions on the activities of the members of State Commissions or Alternative...

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... submission of the application, officers, directors, trustees, full-time volunteers or employees. The... a quorum. If this general restriction creates a situation in which a Commission or AAE does not have... matters relating to the Commission or AAE....

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

    PubMed

    Coleman, Paul C; Bale, Jeffrey S; Hayward, Scott A L

    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

  15. 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

  16. Scaling and extended scaling in sediment registers of a paleolake perturbed by volcanic activity

    NASA Astrophysics Data System (ADS)

    Ugalde, Edgardo; Martínez-Mekler, Gustavo; Vilaclara, Gloria

    2006-07-01

    We analyze a sequence of density variations of sedimentary material from an extinct paleolake of the state of Tlaxcala, Mexico, which we previously obtained by means of computer-aided tomography [J. Miranda, A. Oliver, G. Vilaclara, R. Rico-Montiel, V.M. Macias, J.L. Ruvalcava, M.A. Zenteno, Nucl. Instrum. Methods Phys. Res. B 85 (1994) 886]. In the stratified blocks chiselled out of mines at the lake bed, low-density sediments have a high concentration of diatomite, while high-density strata show a considerable amount of material external to the lake, mostly of volcanic origin. Two regions can be distinguished by visual inspection: a darker and older one which we attribute to a strongly externally perturbed regime, and a whiter more recent one which appears to have been subjected to less frequent volcanic perturbations. By means of a scaling analysis of the distribution function of density fluctuations, we show that for the most recent region there is a range of scales where these fluctuations present a self-similar behavior. We attribute this observation to a rare event response, namely, the onset of correlations in the lake relaxation processes to steady-state conditions following intense volcanic disturbances. Based on scaling properties of the structure function, we also show that the complete data series presents extended self-similarity as encountered in turbulence studies [R. Benzi, S. Ciliberto, R. Tripiccione, C. Baudet, F. Massoli, S. Succi, Phys. Rev. E 48 (1993) R29]. Our characterization of the statistical behavior of the density fluctuations contributes to our knowledge of the volcanic activity over a period of thousands of years, as well as aspects of ecological interest of the lake's response to these disturbances [G. Vilaclara, E. Ugalde, E. Cuna, G. Martinez-Mekler, Complex dynamics of the evolution of a Paleolake subjected to volcanic activity: geology meets ecology, submitted for publication]. Our approach can be implemented in general to other

  17. 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.

  18. The closed/open model for lipase activation. Addressing intermediate active forms of fungal enzymes by trapping of conformers in water-restricted environments.

    PubMed

    González-Navarro, H; Bañó, M C; Abad, C

    2001-03-13

    The behavior of prototypic fungal lipases in a water-restricted environment has been investigated by exploiting the reported experimental strategy that allows the trapping (freeze-drying) of the enzyme in the conformation present in aqueous solution and to subsequently assay it in nonaqueous media [Mingarro, I., Abad, C., and Braco, L. (1995) Proc. Natl. Acad. Sci. U.S.A. 92, 3308-3312]. We now report, using simple esterification as well as acidolysis (triglycerides as substrates) as nonaqueous model reactions, that the presence of a detergent (n-octyl-beta-glucopyranoside) in the freeze-drying buffer, at concentrations below the critical micellar concentration, generates different catalytically active (kinetically trapped) conformational states of the enzyme. These activated forms exquisitely discriminate between short- and long-chain fatty acids, suggesting that they can be correlated with intermediate conformations of the protein sufficiently open to permit the access of relatively small but not large substrates. Additional data obtained from aqueous solution activity measurements in the presence of detergent revealed that the fungal lipase retains an active conformation induced by high detergent concentration (30 mM) for a long period of time, a 'memory effect', which is stabilized in the absence of a well-defined interface by few detergent molecules. Together these results provide support to a model of lipase action involving several equilibrium states (closed, intermediate, and open), which can be modulated by the composition of the microenvironment, i.e., by the detergent concentration.

  19. Speckle imaging of solar small scale structure. 2: Study of small scale structure in active regions

    NASA Astrophysics Data System (ADS)

    von der Luehe, O.

    1994-01-01

    The speckle imaging technique which is described in the first paper of this series (von der Luehe 1993) was used to analyze time series of high angular resolution images of solar small scale structure at a wavelength of 585 nm in active regions with the 76 cm diameter vacuum tower telescope at National Solar Observatory (NSO)/Sac Peak. Two sets of reconstructed images with a field of 4 by 4 arcsec which cover a period of 36 min and 83 min were generated and analyzed. The image reconstructions are supplemented with simultaneous large field photographs taken within a 15 A passband centered on the Ca II K (3933) line. The prime objective of the observing program was the study of the structure and the dynamics of the continuum wavelength counterpart of facular points which appear with high contrast in the Ca pictures, i.e., continuum bright points (CBPs). In addition to CBPs, the reconstructions allow studying other small scale phenomena. Results of the studies are given.

  20. 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.

  1. Active galactic nuclei as scaled-up Galactic black holes.

    PubMed

    McHardy, I M; Koerding, E; Knigge, C; Uttley, P; Fender, R P

    2006-12-07

    A long-standing question is whether active galactic nuclei (AGN) vary like Galactic black hole systems when appropriately scaled up by mass. If so, we can then determine how AGN should behave on cosmological timescales by studying the brighter and much faster varying Galactic systems. As X-ray emission is produced very close to the black holes, it provides one of the best diagnostics of their behaviour. A characteristic timescale--which potentially could tell us about the mass of the black hole--is found in the X-ray variations from both AGN and Galactic black holes, but whether it is physically meaningful to compare the two has been questioned. Here we report that, after correcting for variations in the accretion rate, the timescales can be physically linked, revealing that the accretion process is exactly the same for small and large black holes. Strong support for this linkage comes, perhaps surprisingly, from the permitted optical emission lines in AGN whose widths (in both broad-line AGN and narrow-emission-line Seyfert 1 galaxies) correlate strongly with the characteristic X-ray timescale, exactly as expected from the AGN black hole masses and accretion rates. So AGN really are just scaled-up Galactic black holes.

  2. Lv4 Is a Capsid-Specific Antiviral Activity in Human Blood Cells That Restricts Viruses of the SIVMAC/SIVSM/HIV-2 Lineage Prior to Integration.

    PubMed

    Pizzato, Massimo; McCauley, Sean Matthew; Neagu, Martha R; Pertel, Thomas; Firrito, Claudia; Ziglio, Serena; Dauphin, Ann; Zufferey, Madeleine; Berthoux, Lionel; Luban, Jeremy

    2015-07-01

    HIV-2 and SIVMAC are AIDS-causing, zoonotic lentiviruses that jumped to humans and rhesus macaques, respectively, from SIVSM-bearing sooty mangabey monkeys. Cross-species transmission events such as these sometimes necessitate virus adaptation to species-specific, host restriction factors such as TRIM5. Here, a new human restriction activity is described that blocks viruses of the SIVSM/SIVMAC/HIV-2 lineage. Human T, B, and myeloid cell lines, peripheral blood mononuclear cells and dendritic cells were 4 to >100-fold less transducible by VSV G-pseudotyped SIVMAC, HIV-2, or SIVSM than by HIV-1. In contrast, transduction of six epithelial cell lines was equivalent to that by HIV-1. Substitution of HIV-1 CA with the SIVMAC or HIV-2 CA was sufficient to reduce HIV-1 transduction to the level of the respective vectors. Among such CA chimeras there was a general trend such that CAs from epidemic HIV-2 Group A and B isolates were the most infectious on human T cells, CA from a 1° sooty mangabey isolate was the least infectious, and non-epidemic HIV-2 Group D, E, F, and G CAs were in the middle. The CA-specific decrease in infectivity was observed with either HIV-1, HIV-2, ecotropic MLV, or ALV Env pseudotypes, indicating that it was independent of the virus entry pathway. As2O3, a drug that suppresses TRIM5-mediated restriction, increased human blood cell transduction by SIVMAC but not by HIV-1. Nonetheless, elimination of TRIM5 restriction activity did not rescue SIVMAC transduction. Also, in contrast to TRIM5-mediated restriction, the SIVMAC CA-specific block occurred after completion of reverse transcription and the formation of 2-LTR circles, but before establishment of the provirus. Transduction efficiency in heterokaryons generated by fusing epithelial cells with T cells resembled that in the T cells, indicative of a dominant-acting SIVMAC restriction activity in the latter. These results suggest that the nucleus of human blood cells possesses a restriction factor

  3. Diencephalic Size Is Restricted by a Novel Interplay Between GCN5 Acetyltransferase Activity and Retinoic Acid Signaling.

    PubMed

    Wilde, Jonathan J; Siegenthaler, Julie A; Dent, Sharon Y R; Niswander, Lee A

    2017-03-08

    Diencephalic defects underlie an array of neurological diseases. Previous studies have suggested that retinoic acid (RA) signaling is involved in diencephalic development at late stages of embryonic development, but its roles and mechanisms of action during early neural development are still unclear. Here we demonstrate that mice lacking enzymatic activity of the acetyltransferase GCN5 ((Gcn5(hat/hat) )), which were previously characterized with respect to their exencephalic phenotype, exhibit significant diencephalic expansion, decreased diencephalic RA signaling, and increased diencephalic WNT and SHH signaling. Using a variety of molecular biology techniques in both cultured neuroepithelial cells treated with a GCN5 inhibitor and forebrain tissue from (Gcn5(hat/hat) ) embryos, we demonstrate that GCN5, RARα/γ, and the poorly characterized protein TACC1 form a complex in the nucleus that binds specific retinoic acid response elements in the absence of RA. Furthermore, RA triggers GCN5-mediated acetylation of TACC1, which results in dissociation of TACC1 from retinoic acid response elements and leads to transcriptional activation of RA target genes. Intriguingly, RA signaling defects caused by in vitro inhibition of GCN5 can be rescued through RA-dependent mechanisms that require RARβ. Last, we demonstrate that the diencephalic expansion and transcriptional defects seen in (Gcn5(hat/hat) ) mutants can be rescued with gestational RA supplementation, supporting a direct link between GCN5, TACC1, and RA signaling in the developing diencephalon. Together, our studies identify a novel, nonhistone substrate for GCN5 whose modification regulates a previously undescribed, tissue-specific mechanism of RA signaling that is required to restrict diencephalic size during early forebrain development.SIGNIFICANCE STATEMENT Changes in diencephalic size and shape, as well as SNPs associated with retinoic acid (RA) signaling-associated genes, have been linked to neuropsychiatric

  4. 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

  5. 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.

  6. 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

  7. Activation of NLRC4 by flagellated bacteria triggers caspase-1-dependent and -independent responses to restrict Legionella pneumophila replication in macrophages and in vivo.

    PubMed

    Pereira, Marcelo S F; Morgantetti, Giuliano F; Massis, Liliana M; Horta, Catarina V; Hori, Juliana I; Zamboni, Dario S

    2011-12-15

    Although NLRC4/IPAF activation by flagellin has been extensively investigated, the downstream signaling pathways and the mechanisms responsible for infection clearance remain unclear. In this study, we used mice deficient for the inflammasome components in addition to wild-type (WT) Legionella pneumophila or bacteria deficient for flagellin (flaA) or motility (fliI) to assess the pathways responsible for NLRC4-dependent growth restriction in vivo and ex vivo. By comparing infections with WT L. pneumophila, fliI, and flaA, we found that flagellin and motility are important for the colonization of the protozoan host Acanthamoeba castellanii. However, in macrophages and mammalian lungs, flagellin expression abrogated bacterial replication. The flagellin-mediated growth restriction was dependent on NLRC4, and although it was recently demonstrated that NLRC4 is able to recognize bacteria independent of flagellin, we found that the NLRC4-dependent restriction of L. pneumophila multiplication was fully dependent on flagellin. By examining infected caspase-1(-/-) mice and macrophages with flaA, fliI, and WT L. pneumophila, we could detect greater replication of flaA, which suggests that caspase-1 only partially accounted for flagellin-dependent growth restriction. Conversely, WT L. pneumophila multiplied better in macrophages and mice deficient for NLRC4 compared with that in macrophages and mice deficient for caspase-1, supporting the existence of a novel caspase-1-independent response downstream of NLRC4. This response operated early after macrophage infection and accounted for the restriction of bacterial replication within bacteria-containing vacuoles. Collectively, our data indicate that flagellin is required for NLRC4-dependent responses to L. pneumophila and that NLRC4 triggers caspase-1-dependent and -independent responses for bacterial growth restriction in macrophages and in vivo.

  8. 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...

  9. 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...

  10. Study of Procedures for Determining the Least Restrictive Environment (LRE) Placement of Handicapped Children. Final Report. Activity 3: Legal Analysis.

    ERIC Educational Resources Information Center

    Applied Management Sciences, Inc., Silver Spring, MD.

    The study examined standards applied by judges and hearing officers in deciding disputes related to the least restrictive environment (LRE) placement of handicapped children. The historical basis of the requirement is reviewed, focusing on court decisions; the requirements of P.L. 94-142, the Education for All Handicapped Children Act regarding…

  11. 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.

  12. 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.

  13. Large-scale field trials of active immunizing agents

    PubMed Central

    Cockburn, W. Charles

    1955-01-01

    In this discussion of the methods to be used in large-scale field trials of active immunizing agents and of the results to be expected from such trials, special emphasis is laid on pertussis vaccine trials in Great Britain. After a review of the criteria for strictly controlled field studies and of the investigation of typhoid vaccines conducted in 1904-08 by the Antityphoid Committee of the British Army, the author describes the pertussis vaccine studies which have been and are now being carried by the Whooping-Cough Immunization Committee of the Medical Research Council of Great Britain. The original strictly controlled trials have been completed and the results published. Studies are now being made of vaccines prepared by different methods and evaluated both in the field and in the laboratory. Each vaccine is given to some 2000-3000 children of 4-6 months to 4 years of age. By the end of the studies 30 000-40 000 children will have been followed up for a period of two years. Since in the current studies all the children are vaccinated and none are left as unvaccinated controls, the relative and not the absolute protective value of the vaccines will be measured. PMID:13270079

  14. Patterns of Naturally Occurring Restriction Map Variation, Dopa Decarboxylase Activity Variation and Linkage Disequilibrium in the Ddc Gene Region of Drosophila Melanogaster

    PubMed Central

    Aquadro, C. F.; Jennings-Jr, R. M.; Bland, M. M.; Laurie, C. C.; Langley, C. H.

    1992-01-01

    Forty-six second-chromosome lines of Drosophila melanogaster isolated from five natural populations were surveyed for restriction map variation in a 65-kb region surrounding the gene (Ddc) encoding dopa decarboxylase (DDC). Sixty-nine restriction sites were scored, 13 of which were polymorphic. Average heterozygosity per nucleotide was estimated to be 0.005. Eight large (0.7-5.0 kb) inserts, two small inserts (100 and 200 bp) and three small deletions (100-300 bp) were also observed across the 65-kb region. We see no evidence for a reduction in either nucleotide heterozygosity or insertion/deletion variation in the central 26-kb segment containing Ddc and a dense cluster of lethal complementation groups and transcripts (>/=9 genes) compared to that seen in the adjacent regions (totaling 39 kb) in which only a single gene and transcript has been detected, or to that observed for other gene regions in D. melanogaster. The distribution of restriction site variation shows no significant departure from that expected under an equilibrium neutral model. However insertions and deletions show a significant departure from neutrality in that they are too rare in frequency, consistent with them being deleterious on average. Significant linkage disequilibrium among variants exists across much of the 65-kb region. Lower regional rates of recombination combined with the influence of polymorphic chromosomal inversions, rather than epistatic selection among genes in the dense cluster, probably are sufficient explanations for the creation and/or maintenance of the linkage disequilibrium observed in the Ddc region. We have also assayed adult DDC enzyme activity in these same lines. Twofold variation in activity among lines is observed within our sample. Significant associations are observed between level of DDC enzyme activity and restriction map variants. Surprisingly, one line with a 5.0-kb insert within an intron and one line with a 1.5-kb insert near the 5' end of Ddc each show

  15. A general fluorescent sensor design strategy for "turn-on" activity detection of exonucleases and restriction endonucleases based on graphene oxide.

    PubMed

    Zhang, Qi; Kong, De-Ming

    2013-11-07

    Using graphene oxide (GO) as a nanoquencher, a universal sensor design strategy was developed on the basis of significantly different binding affinities of GO to single-stranded DNAs (ss-DNAs) with different lengths. The proposed sensors could be used for the activity detection of both exonucleases and restriction endonucleases. To achieve this, a single-labeled fluorescent oligonucleotide probe, which had a single-stranded structure or a hairpin structure with a long single-stranded loop, was used. Such a probe could be efficiently absorbed on the surface of GO, resulting in the quenching of the fluorescent signal. Excision of the single-stranded probe by exonucleases or site-specific cleavage at the double-stranded stem of the hairpin probe by restriction endonuclease released fluorophore-labeled nucleotide, which could not be efficiently absorbed by GO, thus leading to increase in fluorescence of the corresponding sensing system. As examples, three sensors, which were used for activity detection of the exonuclease Exo 1 and the restriction endonucleases EcoR I and Hind III, were developed. These three sensors could specifically and sensitively detect the activities of Exo 1, EcoR I and Hind III with detection limits of 0.03 U mL(-1), 0.06 U mL(-1) and 0.04 U mL(-1), respectively. Visual detection was also possible.

  16. A positive role for nucleosome mobility in the transcriptional activity of chromatin templates: restriction by linker histones.

    PubMed Central

    Ura, K; Hayes, J J; Wolffe, A P

    1995-01-01

    Nucleosome mobility facilitates the transcription of chromatin templates containing only histone octamers. Inclusion of linker histones in chromatin inhibits nucleosome mobility, directs nucleosome positioning and represses transcription. Transcriptional repression by linker histone occurs preferentially on templates associated with histone octamers relative to naked DNA. Mobile nucleosomes and the restriction of mobility by linker histones might be expected to exert a major influence on the accessibility of chromatin to regulatory molecules. Images PMID:7641694

  17. 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

  18. Calorie restriction and stroke

    PubMed Central

    2011-01-01

    Stroke, a major cause of disability and mortality in the elderly, occurs when a cerebral blood vessel is occluded or ruptured, resulting in ischemic damage and death of brain cells. The injury mechanism involves metabolic and oxidative stress, excitotoxicity, apoptosis and inflammatory processes, including activation of glial cells and infiltration of leukocytes. In animal models, dietary energy restriction, by daily calorie reduction (CR) or intermittent fasting (IF), extends lifespan and decreases the development of age-related diseases. Dietary energy restriction may also benefit neurons, as suggested by experimental evidence showing that CR and IF protect neurons against degeneration in animal models. Recent findings by our group and others suggest the possibility that dietary energy restriction may protect against stroke induced brain injury, in part by inducing the expression of neurotrophic factors, such as brain-derived neurotrophic factor (BDNF) and basic fibroblast growth factor (bFGF); protein chaperones, including heat shock protein 70 (Hsp70) and glucose regulated protein 78 (GRP78); antioxidant enzymes, such as superoxide dismutases (SOD) and heme oxygenase-1 (HO-1), silent information regulator T1 (SIRT1), uncoupling proteins and anti-inflammatory cytokines. This article discusses the protective mechanisms activated by dietary energy restriction in ischemic stroke. PMID:21910904

  19. The accessibility of thiophosphorylated groups in DNA fragments to the enzymatic activity of ligases and restriction endonuclease Bbs I.

    PubMed

    Schenk, J A; Heymann, S; Micheel, B

    1995-08-01

    The aim of this paper was to test the possibility to ligate and hydrolyse DNA sequences containing thiomodified ends and bonds. T4 DNA ligase was shown to ligate DNA fragments regardless of whether it contains phosphorylated or thiophosphorylated 5'-end. But the cleavage of an internally thiomodified phosphodiester bond was found to be totally inhibited when using the non-palindromic restrictase Bbs I. The special properties of this restriction endonuclease should allow the development of an oriented cloning strategy when combined with T4 ligase and a thiophosphorylation of DNA fragments.

  20. 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 ...

  1. K restriction inhibits protein phosphatase 2B (PP2B) and suppression of PP2B decreases ROMK channel activity in the CCD

    PubMed Central

    Zhang, Yan; Lin, Dao-Hong; Wang, Zhi-Jian; Jin, Yan; Yang, Baofeng; Wang, Wen-Hui

    2009-01-01

    We used Western blot analysis to examine the effect of dietary K intake on the expression of serine/threonine protein phosphatase in the kidney. K restriction significantly decreased the expression of catalytic subunit of protein phosphatase (PP)2B but increased the expression of PP2B regulatory subunit in both rat and mouse kidney. However, K depletion did not affect the expression of PP1 and PP2A. Treatment of M-1 cells, mouse cortical collecting duct (CCD) cells, or 293T cells with glucose oxidase (GO), which generates superoxide anions through glucose metabolism, mimicked the effect of K restriction on PP2B expression and significantly decreased expression of PP2B catalytic subunits. However, GO treatment increased expression of regulatory subunit of PP2B and had no effect on expression of PP1, PP2A, and protein tyrosine phosphatase 1D. Moreover, deletion of gp91-containing NADPH oxidase abolished the effect of K depletion on PP2B. Thus superoxide anions or related products may mediate the inhibitory effect of K restriction on the expression of PP2B catalytic subunit. We also used patch-clamp technique to study the effect of inhibiting PP2B on renal outer medullary K (ROMK) channels in the CCD. Application of cyclosporin A or FK506, inhibitors of PP2B, significantly decreased ROMK channels, and the effect of PP2B inhibitors was abolished by blocking p38 mitogen-activated protein kinase (MAPK) and ERK. Furthermore, Western blot demonstrated that inhibition of PP2B with cyclosporin A or small interfering RNA increased the phosphorylation of ERK and p38 MAPK. We conclude that K restriction suppresses the expression of PP2B catalytic subunits and that inhibition of PP2B decreases ROMK channel activity through stimulation of MAPK in the CCD. PMID:18184875

  2. 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

  3. 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.

  4. 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

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

    PubMed

    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/m(2); 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.

  6. 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

  7. 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…

  8. Restricting feeding to the active phase in middle-aged mice attenuates adverse metabolic effects of a high-fat diet.

    PubMed

    Duncan, M J; Smith, J T; Narbaiza, J; Mueez, F; Bustle, L B; Qureshi, S; Fieseler, C; Legan, S J

    2016-12-01

    Time-restricted feeding ameliorates the deleterious effects of a high-fat diet on body weight and metabolism in young adult mice. Because obesity is highly prevalent in the middle-aged population, this study tested the hypothesis that time-restricted feeding alleviates the adverse effects of a high-fat diet in male middle-aged (12months) mice. C57BL6/J mice were fed one of three diets for 21-25weeks: 1) high-fat diet (60% total calories from fat) ad-libitum (HFD-AL), 2) HFD, time-restricted feeding (HFD-TRF), and 3) low-fat diet (10% total calories from fat) ad-libitum (LFD-AL) (n=15 each). HFD-TRF mice only had food access for 8h/day during their active period. HFD-TRF mice gained significantly less weight than HFD-AL mice (~20% vs 55% of initial weight, respectively). Caloric intake differed between these groups only during the first 8weeks and accounted for most but not all of their body weight difference during this time. TRF of a HFD lowered glucose tolerance in terms of incremental area under the curve (iAUC) (p<0.02) to that of LFD-AL mice. TRF of a HFD lowered liver weight (p<0.0001), but not retroperitoneal or epididymal fat pad weight, to that of LFD-AL mice. Neither HFD-AL nor HFD-TRF had any effect on performance in the novel object recognition or object location memory tests. Circulating corticosterone levels either before or after restraint stress were not affected by diet. In conclusion, TRF without caloric restriction is an effective strategy in middle-aged mice for alleviating the negative effects of a HFD on body weight, liver weight, and glucose tolerance.

  9. 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

  10. 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

  11. Cyclin A-dependent phosphorylation of the ETS-related protein, MEF, restricts its activity to the G1 phase of the cell cycle.

    PubMed

    Miyazaki, Y; Boccuni, P; Mao, S; Zhang, J; Erdjument-Bromage, H; Tempst, P; Kiyokawa, H; Nimer, S D

    2001-11-02

    MEF, a recently identified member of the E74 family of ETS-related transcription factors, is a strong transcriptional activator of cytokine gene expression. Using a green fluorescent protein gene reporter plasmid regulated by an MEF-responsive promoter, we determined that the transcriptional activity of MEF is largely restricted to the G1 phase of the cell cycle. MEF-dependent transcription was suppressed by the expression of cyclin A but not by cyclin D or cyclin E. This effect was due to the kinase activity generated by cyclin A expression, as co-expression of the cyclin-dependent kinase inhibitors p21 or p27, or a dominant negative form of CDK2 (DNK2), abrogated the reduction of MEF transcriptional activity by cyclin A. Cyclin A-CDK2 phosphorylated MEF protein in vitro more efficiently than cyclin D-CDK4 or cyclin E-CDK2, and phosphorylation of MEF by cyclin A-CDK2 reduced its ability to bind DNA. We determined one site of phosphorylation by cyclin A-CDK2 at the C terminus of MEF, using mass-spectrometry; mutation of three serine or threonine residues in this region significantly reduced phosphorylation of MEF by cyclin A and reduced cyclin A-mediated suppression of its transactivating activity. These amino acid substitutions also reduced the restriction of MEF activity to G1. Phosphorylation of MEF by the cyclin A-CDK2 complex controls its transcriptional activity during the cell cycle, establishing a novel link between the ETS family of proteins and the cell cycle machinery.

  12. Effects of short-term exercise training and activity restriction on functional capacity in patients with severe chronic congestive heart failure.

    PubMed

    Meyer, K; Schwaibold, M; Westbrook, S; Beneke, R; Hajric, R; Görnandt, L; Lehmann, M; Roskamm, H

    1996-11-01

    Previous exercise training studies in patients with chronic congestive heart failure (CHF) were performed for periods lasting > 2 months, and effects of activity restriction on exercise induced-benefits were not systematically assessed. With one exception study, patients were not reported to be transplant candidates. In this random-order crossover study, effects of 3 weeks of exercise training and 3 weeks of activity restriction on functional capacity in 18 hospitalized patients with severe CHF [(mean +/- SEM) age 52 +/- 2 years; ejection fraction 21 +/- 1%; half of them on a transplant waiting list] were assessed. The training program consisted of interval exercise with bicycle ergometer (15 minutes) 5 times weekly, interval treadmill walking (10 minutes), and exercises (20 minutes), each 3 times weekly. With training, the onset of ventilatory threshold was delayed (p < 0.001), with increased work rate by 57% (p < 0.001) and oxygen uptake by 23.7% (p < 0.001). On average, there was a 14.6% decrease in slope of ventilation/carbon dioxide production before the onset of ventilatory threshold (p < 0.05), and ventilatory equivalent of carbon dioxide production by 10.3% (p < 0.01). At the highest comparable work rate (56 +/- 5 W) the following variables were decreased: heart rate (7.3%; p < 0.05), lactate (26.6%; p < 0.001), and ratings of perceived leg fatigue and dyspnea (14.5% and 16.5%; p < 0.001 each). At peak exercise, oxygen uptake was increased by 19.7% (p < 0.01) and oxygen pulse by 14.2% (p < 0.01). There was a correlation of baseline peak oxygen uptake and increase of peak oxygen uptake due to training (r = -0.75; p < 0.004). Independently of the random order, data after activity restriction did not differ significantly from data measured at baseline. Patients with stable, severe CHF can achieve significant improvements in aerobic and ventilatory capacity and symptomology by short-term exercise training using interval exercise methods. Impairments due to

  13. Diffuse glutamine synthetase overexpression restricted to areas of peliosis in a β-catenin-activated hepatocellular adenoma: a potential pitfall in glutamine synthetase interpretation.

    PubMed

    Berry, Ryan S; Gullapalli, Rama R; Wu, Jin; Morris, Katherine; Hanson, Joshua A

    2014-08-01

    Hepatocellular adenomas have recently been classified into four subtypes based on molecular findings: hepatocyte nuclear factor 1α (HNF1α) inactivated, inflammatory/telangiectatic, β-catenin activated, and unclassifiable. β-catenin-activated adenomas have the potential for malignant transformation and are thus important to recognize. Diffuse glutamine synthetase immunohistochemical positivity has been shown to be a reliable surrogate marker for β-catenin activation, though variations in staining patterns may be difficult to interpret. We report a case of a peliotic adenoma that was morphologically consistent with a β-catenin wild-type hepatocellular adenoma but harbored a β-catenin mutation by molecular analysis. The tumor lacked nuclear β-catenin positivity and demonstrated a hitherto undescribed pattern of glutamine synthetase overexpression restricted to areas of peliosis with mostly negative staining in non-peliotic areas. This pattern was initially interpreted as physiologic and may represent a potential pitfall in glutamine synthetase interpretation.

  14. Biochemical Characterization of APOBEC3H Variants: Implications for Their HIV-1 Restriction Activity and mC Modification.

    PubMed

    Gu, Jiang; Chen, Qihan; Xiao, Xiao; Ito, Fumiaki; Wolfe, Aaron; Chen, Xiaojiang S

    2016-11-20

    APOBEC3H (A3H) is the most polymorphic member of the APOBEC3 family. Seven haplotypes (hap I-VII) and four mRNA splicing variants (SV) of A3H have been identified. The various haplotypes differ in anti-HIV activity, which is attributed to differences in protein stability, subcellular distribution, and/or RNA binding and virion packaging. Here, we report the first comparative biochemical studies of all the A3H variants using highly purified proteins. We show that all haplotypes were stably expressed and could be purified to homogeneity by Escherichia coli expression. Surprisingly, four out of the seven haplotypes showed high cytosine (C) deaminase activity, with hap V displaying extremely high activity that was comparable to the highly active A3A. Furthermore, all four haplotypes that were active in C deamination were also highly active on methylated C (mC), with hap II displaying almost equal deamination efficiency on both. The deamination activity of these A3H variants correlates well with their reported anti-HIV activity for the different haplotypes, suggesting that deaminase activity may be an important factor in determining their respective anti-HIV activities. Moreover, mC deamination of A3H displayed a strong preference for the sequence motif of T-mCpG-C/G, which may suggest a potential role in genomic mC modification at the characteristic "CpG" island motif.

  15. 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.

  16. Circulating factors induced by caloric restriction in the nonhuman primate Macaca mulatta activate angiogenic processes in endothelial cells.

    PubMed

    Csiszar, Anna; Sosnowska, Danuta; Tucsek, Zsuzsanna; Gautam, Tripti; Toth, Peter; Losonczy, Gyorgy; Colman, Ricki J; Weindruch, Richard; Anderson, Rozalyn M; Sonntag, William E; Ungvari, Zoltan

    2013-03-01

    Moderate caloric restriction (CR) without malnutrition increases healthspan in virtually every species studied, including nonhuman primates. In mice, CR exerts significant microvascular protective effects resulting in increased microvascular density in the heart and the brain, which likely contribute to enhanced tolerance to ischemia and improved cardiac performance and cognitive function. Yet, the underlying mechanisms by which CR confer microvascular protection remain elusive. To test the hypothesis that circulating factors triggered by CR regulate endothelial angiogenic capacity, we treated cultured human endothelial cells with sera derived from Macaca mulatta on long-term (over 10 years) CR. Cells treated with sera derived from ad-libitum-fed control monkeys served as controls. We found that factors present in CR sera upregulate vascular endothelial growth factor (VEGF) signaling and stimulate angiogenic processes, including endothelial cell proliferation and formation of capillary-like structures. Treatment with CR sera also tended to increase cellular migration (measured by a wound-healing assay using electric cell-substrate impedance sensing [ECIS] technology) and adhesion to collagen. Collectively, we find that circulating factors induced by CR promote endothelial angiogenic processes, suggesting that increased angiogenesis may be a potential mechanism by which CR improves cardiac function and prevents vascular cognitive impairment.

  17. 12 CFR 362.8 - Restrictions on activities of insured state nonmember banks affiliated with certain securities...

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... DEPOSIT INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY ACTIVITIES OF INSURED STATE... with any securities underwriting affiliate company that directly engages in the public sale, distribution or underwriting of stocks, bonds, debentures, notes, or other securities activity, of a type...

  18. The immune adaptor molecule SARM modulates tumor necrosis factor alpha production and microglia activation in the brainstem and restricts West Nile Virus pathogenesis.

    PubMed

    Szretter, Kristy J; Samuel, Melanie A; Gilfillan, Susan; Fuchs, Anja; Colonna, Marco; Diamond, Michael S

    2009-09-01

    Sterile alpha and HEAT/Armadillo motif (SARM) is a highly conserved Toll/interleukin-1 receptor (TIR)-containing adaptor protein that is believed to negatively regulate signaling of the pathogen recognition receptors Toll-like receptor 3 (TLR3) and TLR4. To test its physiological function in the context of a microbial infection, we generated SARM(-/-) mice and evaluated the impact of this deficiency on the pathogenesis of West Nile virus (WNV), a neurotropic flavivirus that requires TLR signaling to restrict infection. Although SARM was preferentially expressed in cells of the central nervous system (CNS), studies with primary macrophages, neurons, or astrocytes showed no difference in viral growth kinetics. In contrast, viral replication was increased specifically in the brainstem of SARM(-/-) mice, and this was associated with enhanced mortality after inoculation with a virulent WNV strain. A deficiency of SARM was also linked to reduced levels of tumor necrosis factor alpha (TNF-alpha), decreased microglia activation, and increased neuronal death in the brainstem after WNV infection. Thus, SARM appears to be unique among the TIR adaptor molecules, since it functions to restrict viral infection and neuronal injury in a brain region-specific manner, possibly by modulating the activation of resident CNS inflammatory cells.

  19. 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

    ... foreign organization engages in the United States are incidental to its international or foreign business... representative office. (2) The following activities are incidental to international or foreign business: (i... INSURANCE CORPORATION REGULATIONS AND STATEMENTS OF GENERAL POLICY INTERNATIONAL BANKING §...

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

    PubMed

    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

    2015-03-31

    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 ICEMlSym(R7A) 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 tRNA(phe) from UUU to UUC within a conserved msi172-encoded motif. FseA activated rdfS expression in the absence of ICEMlSym(R7A), 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 ICEMlSym(R7A)-encoded quorum-sensing antiactivator QseM. Thus, activation of ICEMlSym(R7A) 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 ICEMlSym(R7A) transfer only occurs in a subpopulation of cells in which both qseM expression is repressed and FseA is translated. The architecture of the ICEMlSym(R7A) 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.

  1. Randomised clinical trial: alosetron improves quality of life and reduces restriction of daily activities in women with severe diarrhoea-predominant IBS

    PubMed Central

    Cremonini, F; Nicandro, J P; Atkinson, V; Shringarpure, R; Chuang, E; Lembo, A

    2012-01-01

    Background Patients with irritable bowel syndrome with diarrhoea (IBS-D) experience restriction in daily activities and decreased health-related quality of life (QOL). Aim To investigate effects of alosetron on patient-reported health-related QOL, satisfaction and productivity in women with severe IBS-D. Methods A total of 705 women (severe IBS-D, Rome II criteria) randomised to alosetron 0.5 mg QD, 1 mg QD, 1 mg BID, or placebo for 12 weeks were studied. IBSQOL, treatment satisfaction, daily activities, and lost workplace productivity (LWP) were evaluated at randomisation and Week 12. Results One or more doses of alosetron significantly improved all IBSQOL domains except for sexual function from baseline vs. placebo. The magnitude of IBSQOL changes was consistent with a clinically meaningful effect. Alosetron 0.5 mg QD and 1 mg BID significantly reduced IBS interference with social/leisure activities and LWP from baseline vs. placebo [social/leisure (mean ±S.E.) days lost: −6.7 ± 0.8, −7.0 ± 0.9, P < 0.01; LWP (mean ± S.E.) h lost: −11.0 ± 3.3, −21.1 ± 4.1, P < 0.05 respectively]. Significantly more patients treated with alosetron reported satisfaction vs. placebo. Improvements in IBSQOL, LWP, and treatment satisfaction significantly correlated with global improvement of IBS symptoms. The incidence of adverse events with alosetron was low with constipation being the most commonly reported event. A single case of ischaemic colitis occurred, in a patient receiving alosetron 0.5 mg QD. Conclusions In women with severe IBS-D, alosetron treatment, including 0.5 mg QD, resulted in statistically significant and clinically relevant improvements in health-related QOL, restriction of daily activities and treatment satisfaction over placebo. IBS symptom improvement corresponded with positive changes in IBSQOL, LWP and treatment satisfaction. PMID:22779693

  2. Large-Scale Activity Initiated BY Halo CMEs

    NASA Astrophysics Data System (ADS)

    Chertok, I.; Grechnev, V.

    We summarize results of our recent studies of CME-associated EUV dimmings and coronal waves by `derotated' fixed-difference SOHO/EIT heliograms at 195 Å with 12-min intervals and at 171, 195, 284, 304 Å with 6-h intervals. Correctness of the derotated fixed-difference technique is confirmed by the consideration of the Bastille Day 2000 event. We also demonstrate that long narrow channeled dimmings and anisotropic coronal waves are typical of the complex global solar magnetosphere near the solar cycle maximum. Homology of large-scale dimmings and coronal waves takes place in a series of recurrent eruptive events. Along with dimmings coinciding entirely or partially in all four EIT bands, there exist dimmings that appear different, mainly in the transition-region line of 304 Å and high-temperature coronal line of 284 Å.

  3. Effects of Vitamin D Receptor Activation and Dietary Sodium Restriction on Residual Albuminuria in CKD: The ViRTUE-CKD Trial.

    PubMed

    Keyzer, Charlotte A; van Breda, G Fenna; Vervloet, Marc G; de Jong, Maarten A; Laverman, Gozewijn D; Hemmelder, Marc H; Janssen, Wilbert M T; Lambers Heerspink, Hiddo J; Kwakernaak, Arjan J; Bakker, Stephan J L; Navis, Gerjan; de Borst, Martin H

    2017-04-01

    Reduction of residual albuminuria during single-agent renin-angiotensin-aldosterone blockade is accompanied by improved cardiorenal outcomes in CKD. We studied the individual and combined effects of the vitamin D receptor activator paricalcitol (PARI) and dietary sodium restriction on residual albuminuria in CKD. In a multicenter, randomized, placebo (PLAC)-controlled, crossover trial, 45 patients with nondiabetic CKD stages 1-3 and albuminuria >300 mg/24 h despite ramipril at 10 mg/d and BP<140/90 mmHg were treated for four 8-week periods with PARI (2 μg/d) or PLAC, each combined with a low-sodium (LS) or regular sodium (RS) diet. We analyzed the treatment effect by linear mixed effect models for repeated measurements. In the intention-to-treat analysis, albuminuria (geometric mean) was 1060 (95% confidence interval, 778 to 1443) mg/24 h during RS + PLAC and 990 (95% confidence interval, 755 to 1299) mg/24 h during RS + PARI (P=0.20 versus RS + PLAC). LS + PLAC reduced albuminuria to 717 (95% confidence interval, 512 to 1005) mg/24 h (P<0.001 versus RS + PLAC), and LS + PARI reduced albuminuria to 683 (95% confidence interval, 502 to 929) mg/24 h (P<0.001 versus RS + PLAC). The reduction by PARI beyond the effect of LS was nonsignificant (P=0.60). In the per-protocol analysis restricted to participants with ≥95% compliance with study medication, PARI did provide further albuminuria reduction (P=0.04 LS + PARI versus LS + PLAC). Dietary adherence was good as reflected by urinary excretion of 174±64 mmol Na(+) per day in the combined RS groups and 108±61 mmol Na(+) per day in the LS groups (P<0.001). In conclusion, moderate dietary sodium restriction substantially reduced residual albuminuria during fixed dose angiotensin-converting enzyme inhibition. The additional effect of PARI was small and nonsignificant.

  4. 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.

  5. Can we understand time scales of solar activity?

    NASA Astrophysics Data System (ADS)

    Kremliovsky, M. N.

    1994-05-01

    The dynamo theory of the solar cycle faces numerous difficulties in regard to an explanation of the observed behavior of sunspot activity. In particular, there is an essential irregularity in the sequence of 11(22)-year cycles. In this paper we want to show how the complicated long-term evolution of solar activity can be understood within the framework of a simple model demonstrating low-dimensional chaotic behavior. According to this description we are able to give a definition for the periods of low activity (Global Minima), to describe how the transition to (from) a Global Minimum occurs and to show the role of the 11(22)-year cycle and its phase catastrophe. The explanations of the origin of the Gleissberg cycle and thousand-year variations of solar activity are given. In summary, the independence of the proposed scenario from the particular choice of model is shown. Thus one can formulate dynamics in the language of generalized instabilities which can aid the search for the underlying physical processes.

  6. 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,…

  7. 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.

  8. ATP1B3 Protein Modulates the Restriction of HIV-1 Production and Nuclear Factor κ Light Chain Enhancer of Activated B Cells (NF-κB) Activation by BST-2*

    PubMed Central

    Nishitsuji, Hironori; Sugiyama, Ryuichi; Abe, Makoto; Takaku, Hiroshi

    2016-01-01

    Here, we identify ATP1B3 and fibrillin-1 as novel BST-2-binding proteins. ATP1B3 depletion in HeLa cells (BST-2-positive cells), but not 293T cells (BST-2-negative cells), induced the restriction of HIV-1 production in a BST-2-dependent manner. In contrast, fibrillin-1 knockdown reduced HIV-1 production in 293T and HeLa cells in a BST-2-independent manner. Moreover, NF-κB activation was enhanced by siATP1B3 treatment in HIV-1- and HIV-1ΔVpu-infected HeLa cells. In addition, ATP1B3 silencing induced high level BST-2 expression on the surface of HeLa cells. These results indicate that ATP1B3 is a co-factor that accelerates BST-2 degradation and reduces BST-2-mediated restriction of HIV-1 production and NF-κB activation. PMID:26694617

  9. 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.

  10. Psychometric assessment of the Adolescent Physical Activity Perceived Benefits and Barriers Scales.

    PubMed

    Robbins, Lorraine B; Wu, Tsu-Yin; Sikorskii, Alla; Morley, Blair

    2008-01-01

    The purpose of this study was to psychometrically test the Adolescent Physical Activity Perceived Benefits and Barriers Scales developed for middle-school-age youth. A total of 206 racially diverse 6th, 7th, and 8th graders completed questionnaires at two time points (2 weeks apart). For the 10-item Perceived Benefits Scale and the 9-item Perceived Barriers Scale, test-retest reliability (r = .70; r = .71, respectively) and internal consistency (Cronbach's alpha was .80 and .79, respectively, at time 1) were supported. Principal components analysis with Varimax rotation was employed to assess construct validity. A 2-factor solution emerged for each scale as predicted. The relationship between both scale scores and self-reported physical activity provided additional evidence of validity. Both instruments were found to be reliable and valid for measuring the perceived benefits of and barriers to physical activity in middle school youth.

  11. Instrumental neutron activation analysis of archaeological ceramics: scale and interpretation.

    PubMed

    Bishop, Ronald L; Blackman, M James

    2002-08-01

    Instrumental neutron activation analysis has become a standard technique for the study of the production and distributional patterns of archaeological pottery. Questions once framed within the context of long distance exchange are now focused on issues of subregional and even intrasite levels. The increasing specificity at which these questions are poised requires a high level of analytical precision as we seek to observe statistically and archaeologically significant differences among groups of pottery produced from geographically closely spaced resources or the compositional differences that arise from production behaviors of the producers of the pottery.

  12. 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)…

  13. 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.

  14. 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

  15. Peroxisome proliferator-activated receptor mRNA levels are modified by dietary n-3 fatty acid restriction and energy restriction in the brain and liver of growing rats

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Without dietary sources of long chain (LC) n-3 fatty acids, alpha-linolenic acid (ALA;18:3n-3) is the precursor for docosahexaenoic acid (DHA; 22:6n-3). It is not known how energy restriction (ER) impacts ALA conversion to DHA. We tested the hypothesis that ER reduces LCn-3 content in growing rats ...

  16. Synthesis and structure-activity relationship of novel conformationally restricted analogues of serotonin as 5-HT6 receptor ligands.

    PubMed

    Nirogi, Ramakrishna V S; Kambhampati, Ramasastri; Kothmirkar, Prabhakar; Konda, Jagadishbabu; Bandyala, Thrinath Reddy; Gudla, Parandhama; Arepalli, Sobhanadri; Gangadasari, Narasimhareddy P; Shinde, Anil K; Deshpande, Amol D; Dwarampudi, Adireddy; Chindhe, Anil K; Dubey, Pramod Kumar

    2012-06-01

    5-Hydroxytryptamine 6 receptors (5-HT(6)R) are being perceived as the possible target for treatment of cognitive disorders as well as obesity. The present article deals with the design, synthesis, in vitro binding and structure-activity relationship of a novel series of tetracyclic tryptamines with the rigidized N-arylsulphonyl, N-arylcarbonyl and N-benzyl substituents as 5-HT(6) receptor ligands. The chiral sulphonyl derivatives 15a and 17a showed high affinity at 5-HT(6)R with the K(i) of 23.4 and 20.5 nM, respectively. The lead compound from the series 15a has acceptable ADME properties, adequate brain penetration and is active in animal models of cognition like Novel Object Recognition Task (NORT) and water maze.

  17. Cardiac tissue-restricted deletion of plakoglobin results in progressive cardiomyopathy and activation of {beta}-catenin signaling.

    PubMed

    Li, Jifen; Swope, David; Raess, Natalia; Cheng, Lan; Muller, Eliane J; Radice, Glenn L

    2011-03-01

    Mutations in the plakoglobin (JUP) gene have been identified in arrhythmogenic right ventricular cardiomyopathy (ARVC) patients. However, the mechanisms underlying plakoglobin dysfunction involved in the pathogenesis of ARVC remain poorly understood. Plakoglobin is a component of both desmosomes and adherens junctions located at the intercalated disc (ICD) of cardiomyocytes, where it functions to link cadherins to the cytoskeleton. In addition, plakoglobin functions as a signaling protein via its ability to modulate the Wnt/β-catenin signaling pathway. To investigate the role of plakoglobin in ARVC, we generated an inducible cardiorestricted knockout (CKO) of the plakoglobin gene in mice. Plakoglobin CKO mice exhibited progressive loss of cardiac myocytes, extensive inflammatory infiltration, fibrous tissue replacement, and cardiac dysfunction similar to those of ARVC patients. Desmosomal proteins from the ICD were decreased, consistent with altered desmosome ultrastructure in plakoglobin CKO hearts. Despite gap junction remodeling, plakoglobin CKO hearts were refractory to induced arrhythmias. Ablation of plakoglobin caused increase β-catenin stabilization associated with activated AKT and inhibition of glycogen synthase kinase 3β. Finally, β-catenin/TCF transcriptional activity may contribute to the cardiac hypertrophy response in plakoglobin CKO mice. This novel model of ARVC demonstrates for the first time how plakoglobin affects β-catenin activity in the heart and its implications for disease pathogenesis.

  18. 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.

  19. 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.

  20. 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

  1. Mild caloric restriction reduces blood pressure and activates endothelial AMPK-PI3K-Akt-eNOS pathway in obese Zucker rats.

    PubMed

    García-Prieto, C F; Pulido-Olmo, H; Ruiz-Hurtado, G; Gil-Ortega, M; Aranguez, I; Rubio, M A; Ruiz-Gayo, M; Somoza, B; Fernández-Alfonso, M S

    2015-01-01

    Genetic obesity models exhibit endothelial dysfunction associated to adenosine monophosphate-activated protein kinase (AMPK) dysregulation. This study aims to assess if mild short-term caloric restriction (CR) restores endothelial AMPK activity leading to an improvement in endothelial function. Twelve-week old Zucker lean and obese (fa/fa) male rats had access to standard chow either ad libitum (AL, n=8) or 80% of AL (CR, n=8) for two weeks. Systolic blood pressure was significantly higher in fa/fa AL rats versus lean AL animals, but was normalized by CR. Endothelium-dependent relaxation to acetylcholine (ACh, 10(-9) to 10(-4) M) was reduced in fa/fa AL compared to control lean AL rats (p<0.001), and restored by CR. The AMPK activator AICAR (10(-5) to 8·10(-3) M) elicited a lower relaxation in fa/fa AL rings that was normalized by CR (p<0.001). Inhibition of PI3K (wortmannin, 10(-7) M), Akt (triciribine, 10(-5) M), or eNOS (L-NAME, 10(-4) M) markedly reduced AICAR-induced relaxation in lean AL, but not in fa/fa AL rats. These inhibitions were restored by CR in Zucker fa/fa rings. These data show that mild short-term CR improves endothelial function and lowers blood pressure in obesity due to the activation of the AMPK-PI3K-Akt-eNOS pathway.

  2. Fetal growth restriction in hypothyroidism is associated with changes in proliferative activity, apoptosis and vascularisation of the placenta.

    PubMed

    Silva, Juneo F; Vidigal, Paula N; Galvão, Daniele D; Boeloni, Jankerle N; Nunes, Philipe Pimenta; Ocarino, Natália M; Nascimento, Ernane F; Serakides, Rogéria

    2012-01-01

    The objective of this study was to evaluate fetal weight, histomorphometric changes and proliferative activity, apoptosis and angiogenesis of the placenta in rats with hypothyroidism. Thirty-six adult female rats were divided into two groups with 18 animals each: control and hypothyroidism. Hypothyroidism was induced by daily administration of propylthiouracil (1 mg/animal). The administration began five days before becoming pregnant and the animals were sacrificed at 14 or 19 days of gestation. The control group received a placebo. The number and weight of fetuses and the rate of fetal death was determined, as well as the morphometric characteristics, the immunohistochemical expression of cell division control protein 47 (CDC)-47 and vascular endothelial growth factor (VEGF) and the number of apoptotic cells in the placental disk. The data were analysed by Mann-Whitney U test. Hypothyroidism reduced the weight of fetuses and of the uterus and placenta (P<0.05), altered the thickness of the placental labyrinth and spongiotrophoblast (P<0.05), increased the population of glycogen cells in the spongiotrophoblast (P<0.05), interfered with the vascular development of the placental labyrinth and decreased VEGF expression (P<0.05), reduced the expression of CDC-47 and cellularity and increased the apoptotic rate in the placental disk (P<0.05). We conclude that hypothyroidism affects fetal weight by altering the proliferative activity, apoptosis and vascularisation of the placenta.

  3. 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.

  4. 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

  5. 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.

  6. 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.

  7. The Activity Support Scale for Multiple Groups (ACTS-MG): Child-reported Physical Activity Parenting in African American and Non-Hispanic White Families.

    PubMed

    Lampard, Amy M; Nishi, Akihiro; Baskin, Monica L; Carson, Tiffany L; Davison, Kirsten K

    2016-01-01

    This study aimed to assess the psychometric properties of a child-report, multidimensional measure of physical activity (PA) parenting, the Activity Support Scale for Multiple Groups (ACTS-MG), in African American and non-Hispanic white families. The ACTS-MG was administered to children aged 5 to 12 years. A three factor model of PA parenting (Modeling of PA, Logistic Support, and Restricting Access to Screen-based Activities) was tested separately for mother's and fathers' PA parenting. The proposed three-factor structure was supported in both racial groups for mothers' PA parenting and in the African American sample for fathers' PA parenting. Factorial invariance between racial groups was demonstrated for mother's PA parenting. Building on a previous study examining the ACTS-MG parent-report, this study supports the use of the ACTS-MG child-report for mothers' PA parenting. However, further research is required to investigate the measurement of fathers' PA parenting across racial groups.

  8. 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

  9. 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

  10. Scales

    ScienceCinema

    Murray Gibson

    2016-07-12

    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).

  11. 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).

  12. Validation and factorial invariance of children's attraction to physical activity (CAPA) scale in Portugal.

    PubMed

    Seabra, Ana C; Malina, Robert M; Parker, Melissa; Seabra, André; Brustad, Robert; Maia, José A; Fonseca, António M

    2014-01-01

    The Children's Attraction to Physical Activity (CAPA) scale assesses interest in and attraction to the physical activity (PA) of children of elementary school age. The original (25 items) and shorter versions (15 items) of the scale were developed and validated with American children. The purpose of this study was to cross-validate the shorter version of the CAPA scale for use with Portuguese schoolchildren and to examine the invariance of the multidimensional factor structure of the scale in two samples. The sample comprised 683 children (7-10 years) from public primary schools. The sample was divided into calibration and cross-validation samples. The scale was translated into Portuguese and underwent forward translation, synthesis of the translation and backward translation and was then subjected to expert committee review, pretest and reliability assessment. Internal consistency for each of the five subscales within the a priori 5-factor structure of the CAPA scale was evaluated through Cronbach's alpha, followed by a series of confirmatory factor analyses (CFAs) for both the calibration and cross-validation samples. The maximum likelihood robust estimation method was used. The CFA demonstrated that a 5-factor structural model of the Portuguese translation of the CAPA scale was invariant. The construct analysed had the same basic meaning and structural and item differences within the two samples. The results indicated that the CAPA scale is appropriate for use with Portuguese schoolchildren. The availability of a valid and reliable scale should enhance opportunities for further understanding of children's involvement in PA.

  13. Both food restriction and high-fat diet during gestation induce low birth weight and altered physical activity in adult rat offspring: the "Similarities in the Inequalities" model.

    PubMed

    Cunha, Fábio da Silva; Dalle Molle, Roberta; Portella, André Krumel; Benetti, Carla da Silva; Noschang, Cristie; Goldani, Marcelo Zubaran; Silveira, Patrícia Pelufo

    2015-01-01

    We have previously described a theoretical model in humans, called "Similarities in the Inequalities", in which extremely unequal social backgrounds coexist in a complex scenario promoting similar health outcomes in adulthood. Based on the potential applicability of and to further explore the "similarities in the inequalities" phenomenon, this study used a rat model to investigate the effect of different nutritional backgrounds during gestation on the willingness of offspring to engage in physical activity in adulthood. Sprague-Dawley rats were time mated and randomly allocated to one of three dietary groups: Control (Adlib), receiving standard laboratory chow ad libitum; 50% food restricted (FR), receiving 50% of the ad libitum-fed dam's habitual intake; or high-fat diet (HF), receiving a diet containing 23% fat. The diets were provided from day 10 of pregnancy until weaning. Within 24 hours of birth, pups were cross-fostered to other dams, forming the following groups: Adlib_Adlib, FR_Adlib, and HF_Adlib. Maternal chow consumption and weight gain, and offspring birth weight, growth, physical activity (one week of free exercise in running wheels), abdominal adiposity and biochemical data were evaluated. Western blot was performed to assess D2 receptors in the dorsal striatum. The "similarities in the inequalities" effect was observed on birth weight (both FR and HF groups were smaller than the Adlib group at birth) and physical activity (both FR_Adlib and HF_Adlib groups were different from the Adlib_Adlib group, with less active males and more active females). Our findings contribute to the view that health inequalities in fetal life may program the health outcomes manifested in offspring adult life (such as altered physical activity and metabolic parameters), probably through different biological mechanisms.

  14. Calorie restriction minimizes activation of insulin signaling in response to glucose: potential involvement of the growth hormone-insulin-like growth factor 1 axis.

    PubMed

    Hayashi, Hiroko; Yamaza, Haruyoshi; Komatsu, Toshimitsu; Park, Seongjoon; Chiba, Takuya; Higami, Yoshikazu; Nagayasu, Takeshi; Shimokawa, Isao

    2008-09-01

    Calorie restriction (CR) may modulate insulin signaling in response to energy intake through suppression of the growth hormone (GH)-IGF-1 axis. We investigated the glucose-stimulated serum insulin response and subsequent alterations in insulin receptor (IR), Akt, and FoxO1 in the rat liver and quadriceps femoris muscle (QFM). Nine-month-old wild-type (W) male Wistar rats fed ad libitum (AL) or a 30% CR diet initiated at 6 weeks of age and GH-suppressed transgenic (Tg) rats fed AL were killed 15 min after intraperitoneal injection of glucose or saline. In W-AL rats, the serum insulin concentration was elevated by glucose injection. Concomitantly, the phosphorylated (p)-IR and p-Akt levels were increased in both tissues. The active FoxO1 level was decreased in the liver, but not significantly in the QFM. In W-CR and Tg-AL rats, the serum insulin response was lower, and no significant changes were noted for the p-IR, p-Akt, or active FoxO1 levels in the liver. In the QFM, the p-Akt level was increased in W-CR and Tg-AL rats with an insignificant elevation of p-IR levels. The phenotypic similarity of W-CR and Tg-AL rats suggest that CR minimizes activation of insulin signaling in response to energy intake mostly through the GH-IGF-1 axis.

  15. Restricted cortical and amygdaloid removal of vesicular glutamate transporter 2 in preadolescent mice impacts dopaminergic activity and neuronal circuitry of higher brain function.

    PubMed

    Wallén-Mackenzie, Asa; Nordenankar, Karin; Fejgin, Kim; Lagerström, Malin C; Emilsson, Lina; Fredriksson, Robert; Wass, Caroline; Andersson, Daniel; Egecioglu, Emil; Andersson, My; Strandberg, Joakim; Lindhe, Orjan; Schiöth, Helgi B; Chergui, Karima; Hanse, Eric; Långström, Bengt; Fredriksson, Anders; Svensson, Lennart; Roman, Erika; Kullander, Klas

    2009-02-18

    A major challenge in neuroscience is to resolve the connection between gene functionality, neuronal circuits, and behavior. Most, if not all, neuronal circuits of the adult brain contain a glutamatergic component, the nature of which has been difficult to assess because of the vast cellular abundance of glutamate. In this study, we wanted to determine the role of a restricted subpopulation of glutamatergic neurons within the forebrain, the Vglut2-expressing neurons, in neuronal circuitry of higher brain function. Vglut2 expression was selectively deleted in the cortex, hippocampus, and amygdala of preadolescent mice, which resulted in increased locomotor activity, altered social dominance and risk assessment, decreased sensorimotor gating, and impaired long-term spatial memory. Presynaptic VGLUT2-positive terminals were lost in the cortex, striatum, nucleus accumbens, and hippocampus, and a downstream effect on dopamine binding site availability in the striatum was evident. A connection between the induced late-onset, chronic reduction of glutamatergic neurotransmission and dopamine signaling within the circuitry was further substantiated by a partial attenuation of the deficits in sensorimotor gating by the dopamine-stabilizing antipsychotic drug aripiprazole and an increased sensitivity to amphetamine. Somewhat surprisingly, given the restricted expression of Vglut2 in regions responsible for higher brain function, our analyses show that VGLUT2-mediated neurotransmission is required for certain aspects of cognitive, emotional, and social behavior. The present study provides support for the existence of a neurocircuitry that connects changes in VGLUT2-mediated neurotransmission to alterations in the dopaminergic system with schizophrenia-like behavioral deficits as a major outcome.

  16. 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…

  17. 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…

  18. Examining restricted and repetitive behaviors in young children with autism spectrum disorder during two observational contexts.

    PubMed

    Stronach, Sheri; Wetherby, Amy M

    2014-02-01

    This prospective study of the FIRST WORDS® Project examined restricted and repetitive behaviors in a sample of 55 toddlers at a mean age of 20 months who were later diagnosed with autism spectrum disorder. Restricted and repetitive behaviors were coded using the Repetitive Movement and Restricted Interest Scales in two video-recorded observation methods-structured sampling procedures in a clinic and naturalistic everyday activities at home. Measures of restricted and repetitive behaviors were higher in the clinic setting than in the home observation, especially for behaviors involving object use. Repetitive movements with objects in the clinic predicted nonverbal developmental scores and Autism Diagnostic Observation Schedule social affect scores at later follow-up. In contrast, repetitive movements with objects at home significantly predicted later Autism Diagnostic Observation Schedule restricted and repetitive behaviors scores. These results support the utility of the Repetitive Movement and Restricted Interest Scales to detect restricted and repetitive behaviors in toddlers and suggest that observations of restricted and repetitive behaviors in clinic and home settings may provide unique and important diagnostic information for improving early detection of autism spectrum disorder.

  19. 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.

  20. Activity affects intraspecific body-size scaling of metabolic rate in ectothermic animals.

    PubMed

    Glazier, Douglas Stewart

    2009-10-01

    Metabolic rate is commonly thought to scale with body mass (M) to the 3/4 power. However, the metabolic scaling exponent (b) may vary with activity state, as has been shown chiefly for interspecific relationships. Here I use a meta-analysis of literature data to test whether b changes with activity level within species of ectothermic animals. Data for 19 species show that b is usually higher during active exercise (mean +/- 95% confidence limits = 0.918 +/- 0.038) than during rest (0.768 +/- 0.069). This significant upward shift in b to near 1 is consistent with the metabolic level boundaries hypothesis, which predicts that maximal metabolic rate during exercise should be chiefly influenced by volume-related muscular power production (scaling as M (1)). This dependence of b on activity level does not appear to be a simple temperature effect because body temperature in ectotherms changes very little during exercise.

  1. WASP is activated by phosphatidylinositol-4,5-bisphosphate to restrict synapse growth in a pathway parallel to bone morphogenetic protein signaling

    PubMed Central

    Habets, Ron L. P.; Slabbaert, Jan R.; Verstreken, Patrik

    2010-01-01

    Phosphatidylinositol-4,5-bisphosphate [PI(4,5)P2] is a membrane lipid involved in several signaling pathways. However, the role of this lipid in the regulation of synapse growth is ill-defined. Here we identify PI(4,5)P2 as a gatekeeper of neuromuscular junction (NMJ) size. We show that PI(4,5)P2 levels in neurons are critical in restricting synaptic growth by localizing and activating presynaptic Wiscott-Aldrich syndrome protein/WASP (WSP). This function of WSP is independent of bone morphogenetic protein (BMP) signaling but is dependent on Tweek, a neuronally expressed protein. Loss of PI(4,5)P2-mediated WSP activation results in increased formation of membrane-organizing extension spike protein (Moesin)-GFP patches that concentrate at sites of bouton growth. Based on pharmacological and genetic studies, Moesin patches mark polymerized actin accumulations and correlate well with NMJ size. We propose a model in which PI(4,5)P2- and WSP-mediated signaling at presynaptic termini controls actin-dependent synapse growth in a pathway at least in part in parallel to synaptic BMP signaling. PMID:20844206

  2. 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

  3. Scaling Behavior of Human Locomotor Activity Amplitude: Association with Bipolar Disorder

    PubMed Central

    Indic, Premananda; Salvatore, Paola; Maggini, Carlo; Ghidini, Stefano; Ferraro, Gabriella; Baldessarini, Ross J.; Murray, Greg

    2011-01-01

    Scale invariance is a feature of complex biological systems, and abnormality of multi-scale behaviour may serve as an indicator of pathology. The hypothalamic suprachiasmatic nucleus (SCN) is a major node in central neural networks responsible for regulating multi-scale behaviour in measures of human locomotor activity. SCN also is implicated in the pathophysiology of bipolar disorder (BD) or manic-depressive illness, a severe, episodic disorder of mood, cognition and behaviour. Here, we investigated scaling behaviour in actigraphically recorded human motility data for potential indicators of BD, particularly its manic phase. A proposed index of scaling behaviour (Vulnerability Index [VI]) derived from such data distinguished between: [i] healthy subjects at high versus low risk of mood disorders; [ii] currently clinically stable BD patients versus matched controls; and [iii] among clinical states in BD patients. PMID:21655197

  4. 12 CFR 575.11 - Operating restrictions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... Banks and Banking OFFICE OF THRIFT SUPERVISION, DEPARTMENT OF THE TREASURY MUTUAL HOLDING COMPANIES § 575.11 Operating restrictions. (a) Activities restrictions. A mutual holding company may engage in any business activity specified in 12 U.S.C. 1467a(c)(2) or (c)(9)(A)(ii). In addition, the business...

  5. 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

  6. Large-scale assessment of activity landscape feature probabilities of bioactive compounds.

    PubMed

    Kayastha, Shilva; Dimova, Dilyana; Iyer, Preeti; Vogt, Martin; Bajorath, Jürgen

    2014-02-24

    Activity landscape representations integrate pairwise compound similarity and potency relationships and provide direct access to characteristic structure-activity relationship features in compound data sets. Because pairwise compound comparisons provide the foundation of activity landscape design, the assessment of specific landscape features such as activity cliffs has generally been confined to the level of compound pairs. A conditional probability-based approach has been applied herein to assign most probable activity landscape features to individual compounds. For example, for a given data set compound, it was determined if it would preferentially engage in the formation of activity cliffs or other landscape features. In a large-scale effort, we have determined conditional activity landscape feature probabilities for more than 160,000 compounds with well-defined activity annotations contained in 427 different target-based data sets. These landscape feature probabilities provide a detailed view of how different activity landscape features are distributed over currently available bioactive compounds.

  7. 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

  8. 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

  9. Biology of DNA restriction.

    PubMed Central

    Bickle, T A; Krüger, D H

    1993-01-01

    Our understanding of the evolution of DNA restriction and modification systems, the control of the expression of the structural genes for the enzymes, and the importance of DNA restriction in the cellular economy has advanced by leaps and bounds in recent years. This review documents these advances for the three major classes of classical restriction and modification systems, describes the discovery of a new class of restriction systems that specifically cut DNA carrying the modification signature of foreign cells, and deals with the mechanisms developed by phages to avoid the restriction systems of their hosts. PMID:8336674

  10. Genetics of restrictive cardiomyopathy.

    PubMed

    Sen-Chowdhry, Srijita; Syrris, Petros; McKenna, William J

    2010-04-01

    Restrictive physiology, a severe form of diastolic dysfunction, is characteristically observed in the setting of constrictive pericarditis and myocardial restriction. The latter is commonly due to systemic diseases, some of which are inherited as mendelian traits (eg, hereditary amyloidosis), while others are multifactorial (eg, sarcoidosis). When restrictive physiology occurs as an early and dominant feature of a primary myocardial disorder, it may be termed restrictive cardiomyopathy. In the past decade, clinical and genetic studies have demonstrated that restrictive cardiomyopathy as such is part of the spectrum of sarcomeric disease and frequently coexists with hypertrophic cardiomyopathy in affected families.

  11. A Noncanonical Autophagy Pathway Restricts Toxoplasma gondii Growth in a Strain-Specific Manner in IFN-γ-Activated Human Cells

    PubMed Central

    Selleck, Elizabeth M.; Orchard, Robert C.; Lassen, Kara G.; Beatty, Wandy L.; Xavier, Ramnik J.; Levine, Beth; Virgin, Herbert W.

    2015-01-01

    ABSTRACT A core set of autophagy proteins is required for gamma interferon (IFN-γ)-mediated clearance of Toxoplasma gondii in the mouse because of their control of several downstream effectors, including immunity-related GTPases (IRGs) and guanylate-binding proteins (GBPs). However, these effectors are absent (i.e., IRGs) from or nonessential (i.e., GBPs) in IFN-γ-activated human cells, raising the question of how these cells control parasite replication. Here, we define a novel role for ubiquitination and recruitment of autophagy adaptors in the strain-specific control of T. gondii replication in IFN-γ-activated human cells. Vacuoles containing susceptible strains of T. gondii became ubiquitinated, recruited the adaptors p62 and NDP52, and were decorated with LC3. Parasites within LC3-positive vacuoles became enclosed in multiple layers of host membranes, resulting in stunting of parasite replication. However, LC3-positive T. gondii-containing vacuoles did not fuse with endosomes and lysosomes, indicating that this process is fundamentally different from xenophagy, a form of autophagy involved in the control of intracellular bacterial pathogens. Genetic knockout of ATG16L or ATG7 reverted the membrane encapsulation and restored parasite replication, indicating that core autophagy proteins involved in LC3 conjugation are important in the control of parasite growth. Despite a role for the core autophagy machinery in this process, upstream activation through Beclin 1 was not sufficient to enhance the ubiquitination of T. gondii-containing vacuoles, suggesting a lack of reliance on canonical autophagy. These findings demonstrate a new mechanism for IFN-γ-dependent control of T. gondii in human cells that depends on ubiquitination and core autophagy proteins that mediate membrane engulfment and restricted growth. PMID:26350966

  12. One base pair change abolishes the T cell-restricted activity of a kB-like proto-enhancer element from the interleukin 2 promoter.

    PubMed Central

    Briegel, K; Hentsch, B; Pfeuffer, I; Serfling, E

    1991-01-01

    The inducible, T cell-specific enhancers of murine and human Interleukin 2 (Il-2) genes contain the kB-like sequence GGGATTTCACC as an essential cis-acting enhancer motif. When cloned in multiple copies this so-called TCEd (distal T cell element) acts as an inducible proto-enhancer element in E14 T lymphoma cells, but not in HeLa cells. In extracts of induced, Il-2 secreting El4 cells three individual protein factors bind to TCEd DNA. The binding of the most prominent factor, named TCF-1 (T cell factor 1), is correlated with the proto-enhancer activity of TCEd. TCF-1 consists of two polypeptides of about 50 kD and 105 kD; the former seems to be related to the 50 kD polypeptide of NF-kB. Purified NF-kB is also able to bind to the TCEd, but TCF-1 binds stronger than NF-kB to TCEd DNA. The conversion of the TCEd to a 'perfect' NF-kB binding site leads to a tighter binding of NF-kB to TCEd DNA and, as a functional consequence, to the activity of the 'converted' TCEd motifs in HeLa cells. Thus, the substitution of the underlined A residue to a C within the GGGATTTCACC motif abolishes its T cell-restricted activity and leads to its functioning in both El4 cells and HeLa cells. These results indicate that lymphocyte-specific factors binding to the TCEd are involved in the control of T cell specific-transcription of the Il-2 gene. Images PMID:1945879

  13. [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.

  14. The activities-specific balance confidence scale and berg balance scale: Reliability and validity in Arabic-speaking vestibular patients.

    PubMed

    Alghwiri, Alia A; Alghadir, Ahmad H; Al-Momani, Murad O; Whitney, Susan L

    2016-01-01

    Persons with vestibular disorders are susceptible to imbalance. The Activities-specific Balance Confidence (ABC) scale and Berg Balance Scale (BBS) have been validated in persons with vestibular disorders. The purpose of this study was to examine the reliability and validity of the Arabic versions of ABC and BBS among Arabic-speaking persons with vestibular disorders in Jordan and Saudi Arabia. Therefore, the A-ABC and A-BBS were administered to a convenience sample of 82 persons with vestibular disorders (age = 43 ± 14), (56% female). The test-retest reliability of the A-ABC item and total score as well as the inter-rater and intra-rater reliability of the A-BBS total score reflected high agreement. Significant and large correlations were found between the A-ABC and the A-BBS (r= 0.54, P< 0.05), the A-ABC and the Arabic Dizziness Handicap Inventory (A-DHI) (r= -0.76, P< 0.05), and the A-BBS and the A-DHI (r= -0.56, P< 0.05). The A-ABC and the A-BBS demonstrated good reliability and validity and can be utilized with Arabic-speaking persons with vestibular disorders.

  15. Intrauterine growth restriction combined with a maternal high-fat diet increases hepatic cholesterol and low-density lipoprotein receptor activity in rats.

    PubMed

    Zinkhan, Erin K; Zalla, Jennifer M; Carpenter, Jeanette R; Yu, Baifeng; Yu, Xing; Chan, Gary; Joss-Moore, Lisa; Lane, Robert H

    2016-07-01

    Intrauterine growth restriction (IUGR) and maternal consumption of a high-saturated-fat diet (HFD) increase the risk of hypercholesterolemia, a leading cause of morbidity and mortality. Many pregnant women eat a HFD, thus exposing the fetus to a HFD in utero. The cumulative effect of in utero exposure to IUGR and a HFD on offspring cholesterol levels remains unknown. Furthermore, little is known about the mechanism through which IUGR and maternal HFD consumption increase cholesterol. We hypothesize that IUGR combined with a maternal HFD would increase offspring serum and hepatic cholesterol accumulation via alteration in levels of key proteins involved in cholesterol metabolism. To test our hypothesis we used a rat model of surgically induced IUGR and fed the dams a regular diet or a HFD HFD-fed dams consumed the same kilocalories as regular diet-fed dams, with no difference between surgical intervention groups. In the offspring, IUGR combined with a maternal HFD increased hepatic cholesterol levels, low-density lipoprotein (LDL) receptor protein levels, and Ldlr activity in female rat offspring at birth and both sexes at postnatal day 14 relative to non-IUGR offspring both from regular diet- and HFD-fed dams. These findings suggest that IUGR combined with a maternal HFD increases hepatic cholesterol accumulation via increased LDL cholesterol uptake into the liver with resulting persistent increases in hepatic cholesterol accumulation.

  16. Neonatal Growth Restriction-Related Leptin Deficiency Enhances Leptin-Triggered Sympathetic Activation and Central Angiotensin II Receptor-Dependent Stress-Evoked Hypertension

    PubMed Central

    Peotta, Veronica; Rahmouni, Kamal; Segar, Jeffrey L.; Morgan, Donald A.; Pitz, Kate M.; Rice, Olivia M.; Roghair, Robert D.

    2016-01-01

    Background Neonatal growth restriction (nGR) leads to leptin deficiency and increases the risk of hypertension. Previous studies have shown nGR-related hypertension is normalized by neonatal leptin (nLep) and exacerbated by psychological stress. With recent studies linking leptin and angiotensin signaling, we hypothesized that nGR-induced nLep deficiency increases adult leptin sensitivity; leading to leptin- or stress-induced hypertension, through a pathway involving central angiotensin II type 1 receptors. Methods We randomized mice with incipient nGR, by virtue of their presence in large litters, to vehicle or physiologic nLep supplementation (80 ng/g/d). Adult caloric intake and arterial pressure were monitored at baseline, during intracerebroventricular losartan infusion and during systemic leptin administration. Results nGR increased leptin-triggered renal sympathetic activation and hypertension with increased leptin receptor expression in the arcuate nucleus of the hypothalamus; all of those nGR-associated phenotypes were normalized by nLep. nGR mice also had stress-related hyperphagia and hypertension, but only the stress hypertension was blocked by central losartan infusion. Conclusion nGR leads to stress hypertension through a pathway that involves central angiotensin II receptors, and nGR-associated leptin deficiency increases leptin-triggered hypertension in adulthood. These data suggest potential roles for preservation of neonatal growth and nLep supplementation in the prevention of nGR-related hypertension. PMID:27049292

  17. TNF-Mediated Restriction of Arginase 1 Expression in Myeloid Cells Triggers Type 2 NO Synthase Activity at the Site of Infection

    PubMed Central

    Obermeyer, Stephanie; König, Till; Kling, Jessica C.; Ribechini, Eliana; Dudziak, Diana; Mougiakakos, Dimitrios; Murray, Peter J.; Ostuni, Renato; Körner, Heinrich; Bogdan, Christian

    2016-01-01

    Neutralization or deletion of tumor necrosis factor (TNF) causes loss of control of intracellular pathogens in mice and humans, but the underlying mechanisms are incompletely understood. Here, we found that TNF antagonized alternative activation of macrophages and dendritic cells by IL-4. TNF inhibited IL-4-induced arginase (Arg) 1 expression by decreasing histone acetylation, without affecting STAT6 phosphorylation and nuclear translocation. In Leishmania major-infected C57BL/6 wild-type mice, type 2 nitric oxide (NO) synthase (NOS2) was detected in inflammatory dendritic cells/macrophages, some of which coexpressed Arg1. In TNF-deficient mice Arg1 was hyperexpressed causing an impaired production of NO in situ. A similar phenotype was seen in L. major-infected BALB/c mice. Arg1 deletion in hematopoietic cells protected these mice from an otherwise lethal disease, although their disease-mediating T cell response (Th2, Treg) was maintained. Thus, deletion or TNF-mediated restriction of Arg1 unleashes the production of NO by NOS2 which is critical for pathogen control. PMID:27117406

  18. 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.

  19. 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.

  20. Dietary restriction-resistant human tumors harboring the PIK3CA-activating mutation H1047R are sensitive to metformin

    PubMed Central

    Cufí, Sílvia; Corominas-Faja, Bruna; Lopez-Bonet, Eugeni; Bonavia, Rosa; Pernas, Sonia; López, Isabel álvarez; Dorca, Joan; Martínez, Susana; López, Norberto Batista; Fernández, Severina Domínguez; Cuyàs, Elisabet; Visa, Joana; Rodríguez-Gallego, Esther; Quirantes-Piné, Rosa; Segura-Carretero, Antonio; Joven, Jorge; Martin-Castillo, Begoña; Menendez, Javier A.

    2013-01-01

    Cancer cells expressing constitutively active phosphatidylinositol-3 kinase (PI3K) are proliferative regardless of the absence of insulin, and they form dietary restriction (DR)-resistant tumors in vivo. Because the binding of insulin to its receptors activates the PI3K/AKT/mammalian target of rapamycin (mTOR) signaling cascade, activating mutations in the PIK3CA oncogene may determine tumor response to DR-like pharmacological strategies targeting the insulin and mTOR pathways. The anti-diabetic drug metformin is a stereotypical DR mimetic that exerts its anti-cancer activity through a dual mechanism involving insulin-related (systemic) and mTOR-related (cell-autonomous) effects. However, it remains unclear whether PIK3CA-activating mutations might preclude the anti-cancer activity of metformin in vivo. To model the oncogenic PIK3CA-driven early stages of cancer, we used the clonal breast cancer cell line MCF10DCIS.com, which harbors the gain-of-function H1047R hot-spot mutation in the catalytic domain of the PI3KCA gene and has been shown to form DR-refractory xenotumors. To model PIK3CA-activating mutations in late stages of cancer, we took advantage of the isogenic conversion of a PIK3CA-wild-type tumor into a PIK3CA H1047R-mutated tumor using the highly metastatic colorectal cancer cell line SW48. MCF10DCIS.com xenotumors, although only modestly affected by treatment with oral metformin (approximately 40% tumor growth inhibition), were highly sensitive to the intraperitoneal (i.p.) administration of metformin, the anti-cancer activity of which increased in a time-dependent manner and reached >80% tumor growth inhibition by the end of the treatment. Metformin treatment via the i.p. route significantly reduced the proliferation factor mitotic activity index (MAI) and decreased tumor cellularity in MCF10DCIS.com cancer tissues. Whereas SW48-wild-type (PIK3CA+/+) cells rapidly formed metformin-refractory xenotumors in mice, ad libitum access to water containing

  1. Human herpesvirus 6A (HHV-6A) exhibits restrictive propagation with limited activation of PKR-eIF2α stress pathway.

    PubMed

    Sharon, Eyal; Frenkel, Niza

    2017-02-15

    (ATF4), known to transcribe stress genes. Overexpression of PKR led to increased eIF2α phosphorylation and decreased viral replication whereas overexpression of dominant-negative PKR mutant resulted in a moderate increase in viral replication. These results suggest that HHV-6A replication strategy involves restricted activation of the PKR-eIF2α pathway, partial translation inhibition and lower yields of infectious virus. In essence, HHV-6A limits its own replication due to the inability to bypass the eIF2α phosphorylation.

  2. 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

  3. 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.

  4. 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.

  5. Plasminogen Activator Inhibitor-1 Deficiency Augments Visceral Mesothelial Organization, Intrapleural Coagulation, and Lung Restriction in Mice with Carbon Black/Bleomycin–Induced Pleural Injury

    PubMed Central

    Jeffers, Ann; Alvarez, Alexia; Owens, Shuzi; Koenig, Kathleen; Quaid, Brandon; Komissarov, Andrey A.; Florova, Galina; Kothari, Hema; Pendurthi, Usha; Mohan Rao, L. Vijaya; Idell, Steven

    2014-01-01

    Local derangements of fibrin turnover and plasminogen activator inhibitor (PAI)-1 have been implicated in the pathogenesis of pleural injury. However, their role in the control of pleural organization has been unclear. We found that a C57Bl/6j mouse model of carbon black/bleomycin (CBB) injury demonstrates pleural organization resulting in pleural rind formation (14 d). In transgenic mice overexpressing human PAI-1, intrapleural fibrin deposition was increased, but visceral pleural thickness, lung volumes, and compliance were comparable to wild type. CBB injury in PAI-1−/− mice significantly increased visceral pleural thickness (P < 0.001), elastance (P < 0.05), and total lung resistance (P < 0.05), while decreasing lung compliance (P < 0.01) and lung volumes (P < 0.05). Collagen, α-smooth muscle actin, and tissue factor were increased in the thickened visceral pleura of PAI-1−/− mice. Colocalization of α-smooth muscle actin and calretinin within pleural mesothelial cells was increased in CBB-injured PAI-1−/− mice. Thrombin, factor Xa, plasmin, and urokinase induced mesothelial–mesenchymal transition, tissue factor expression, and activity in primary human pleural mesothelial cells. In PAI-1−/− mice, D-dimer and thrombin–antithrombin complex concentrations were increased in pleural lavage fluids. The results demonstrate that PAI-1 regulates CBB-induced pleural injury severity via unrestricted fibrinolysis and cross-talk with coagulation proteases. Whereas overexpression of PAI-1 augments intrapleural fibrin deposition, PAI-1 deficiency promotes profibrogenic alterations of the mesothelium that exacerbate pleural organization and lung restriction. PMID:24024554

  6. Leucine supplementation of a chronically restricted protein and energy diet enhances mTOR pathway activation but not muscle protein synthesis in neonatal pigs

    PubMed Central

    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

  7. 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.

  8. Reliability and Validity of the Commitment to Physical Activity Scale for Adolescents.

    PubMed

    Robbins, Lorraine B; Ling, Jiying; Wesolek, Stacey M; Kazanis, Anamaria S; Bourne, Kelly A; Resnicow, Ken

    2016-01-05

    Purpose . To examine psychometric properties of a Commitment to Physical Activity Scale for Adolescents (CPASA). Design . Two test-retest studies and a prospective study, approved by a university institutional review board, were conducted in midwestern U.S. urban areas. Setting . The first test-retest study occurred in four community centers, the second test-retest study took place in a community school, and the prospective study occurred in eight middle schools. Subjects . To measure commitment at baseline and 1 week later, 51 girls in the first test-retest study completed an original 26-item scale, and 91 in the second test-retest study completed a revised 11-item scale. In the prospective study, 503 girls completed the 11-item scale. Measures . Commitment was measured via the CPASA. After completing the CPASA, girls in the prospective study wore ActiGraph GT3X-plus accelerometers that measured light, moderate, and vigorous physical activity (LMVPA) and moderate to vigorous physical activity (MVPA). Analysis . Internal consistency and test-retest reliability were estimated. Both exploratory factor analysis (EFA) and confirmatory factor analysis (CFA) were conducted to cross-validate the factor structure. Results . For the 11-item CPASA, Cronbach α ranged from .81 to .82, and test-retest reliability was .88. Both EFA and CFA indicated a single factor. The scale was significantly correlated with LMVPA (r = .10) and MVPA (r = .11). Conclusion . The 11-item CPASA demonstrated acceptable reliability and validity with girls.

  9. 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.

  10. 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

  11. 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

  12. [Validity and reliability of a scale to assess self-efficacy for physical activity in elderly].

    PubMed

    Borges, Rossana Arruda; Rech, Cassiano Ricardo; Meurer, Simone Teresinha; Benedetti, Tânia Rosane Bertoldo

    2015-04-01

    This study aimed to analyze the confirmatory factor validity and reliability of a self-efficacy scale for physical activity in a sample of 118 elderly (78% women) from 60 to 90 years of age. Mplus 6.1 was used to evaluate the confirmatory factor analysis. Reliability was tested by internal consistency and temporal stability. The original scale consisted of five items with dichotomous answers (yes/no), independently for walking and moderate and vigorous physical activity. The analysis excluded the item related to confidence in performing physical activities when on vacation. Two constructs were identified, called "self-efficacy for walking" and "self-efficacy for moderate and vigorous physical activity", with a factor load ≥ 0.50. Internal consistency was adequate both for walking (> 0.70) and moderate and vigorous physical activity (> 0.80), and temporal stability was adequate for all the items. In conclusion, the self-efficacy scale for physical activity showed adequate validity, reliability, and internal consistency for evaluating this construct in elderly Brazilians.

  13. 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…

  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. Microbial Survey of a Full-Scale, Biologically Active Filter for Treatment of Drinking Water

    PubMed Central

    DeBry, Ronald W.; Lytle, Darren A.

    2012-01-01

    The microbial community of a full-scale, biologically active drinking water filter was surveyed using molecular techniques. Nitrosomonas, Nitrospira, Sphingomonadales, and Rhizobiales dominated the clone libraries. The results elucidate the microbial ecology of biological filters and demonstrate that biological treatment of drinking water should be considered a viable alternative to physicochemical methods. PMID:22752177

  16. 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…

  17. Microbial survey of a full-scale, biologically active filter for treatment of drinking water.

    PubMed

    White, Colin P; Debry, Ronald W; Lytle, Darren A

    2012-09-01

    The microbial community of a full-scale, biologically active drinking water filter was surveyed using molecular techniques. Nitrosomonas, Nitrospira, Sphingomonadales, and Rhizobiales dominated the clone libraries. The results elucidate the microbial ecology of biological filters and demonstrate that biological treatment of drinking water should be considered a viable alternative to physicochemical methods.

  18. 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.

  19. 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…

  20. 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...

  1. Peroxisome proliferator-activated receptor-gamma coactivator-1alpha activation of CYP7A1 during food restriction and diabetes is still inhibited by small heterodimer partner.

    PubMed

    Shin, Dong-Ju; Osborne, Timothy F

    2008-05-30

    Cholesterol 7alpha-hydroxylase (CYP7A1) catalyzes the rate-limiting step in the classic pathway of hepatic bile acid biosynthesis from cholesterol. During fasting and in type I diabetes, elevated levels of peroxisome proliferator-activated receptor gamma-coactivator-1alpha (PGC-1alpha) induce expression of the Cyp7A1 gene and overexpression of PGC-1alpha in hepatoma cells stimulates bile acid synthesis. Using Ad-PGC-1alpha-RNA interference to induce acute disruption of PGC-1alpha in mice, here we show that PGC-1alpha is necessary for fasting-mediated induction of CYP7A1. Co-immunoprecipitation and promoter activation studies reveal that the induction of CYP7A1 is mediated by direct interaction between PGC-1alpha and the AF2 domain of liver receptor homolog-1 (LRH-1). In contrast, the very similar PGC-1beta could not substitute for PGC-1alpha. We also show that transactivation of PGC-1alpha and LRH-1 is repressed by the small heterodimer partner (SHP). Treatment of mice with GW4064, a synthetic agonist for farnesoid X receptor, induced SHP expression and decreased both the recruitment of PGC-1alpha to the Cyp7A1 promoter and the fasting-induced expression of CYP7A1 mRNA. These data suggest that PGC-1alpha is an important co-activator for LRH-1 and that SHP targets the interaction between LRH-1 and PGC-1alpha to inhibit CYP7A1 expression. Overall, these studies provide further evidence for the important role of PGC-1alpha in bile acid homeostasis and suggest that pharmacological targeting of farnesoid X receptor in vivo can be used to reverse the increase in CYP7A1 associated with adverse metabolic conditions.

  2. Activity blockade and GABAA receptor blockade produce synaptic scaling through chloride accumulation in embryonic spinal motoneurons and interneurons.

    PubMed

    Lindsly, Casie; Gonzalez-Islas, Carlos; Wenner, Peter

    2014-01-01

    Synaptic scaling represents a process whereby the distribution of a cell's synaptic strengths are altered by a multiplicative scaling factor. Scaling is thought to be a compensatory response that homeostatically controls spiking activity levels in the cell or network. Previously, we observed GABAergic synaptic scaling in embryonic spinal motoneurons following in vivo blockade of either spiking activity or GABAA receptors (GABAARs). We had determined that activity blockade triggered upward GABAergic scaling through chloride accumulation, thus increasing the driving force for these currents. To determine whether chloride accumulation also underlies GABAergic scaling following GABAAR blockade we have developed a new technique. We expressed a genetically encoded chloride-indicator, Clomeleon, in the embryonic chick spinal cord, which provides a non-invasive fast measure of intracellular chloride. Using this technique we now show that chloride accumulation underlies GABAergic scaling following blockade of either spiking activity or the GABAAR. The finding that GABAAR blockade and activity blockade trigger scaling via a common mechanism supports our hypothesis that activity blockade reduces GABAAR activation, which triggers synaptic scaling. In addition, Clomeleon imaging demonstrated the time course and widespread nature of GABAergic scaling through chloride accumulation, as it was also observed in spinal interneurons. This suggests that homeostatic scaling via chloride accumulation is a common feature in many neuronal classes within the embryonic spinal cord and opens the possibility that this process may occur throughout the nervous system at early stages of development.

  3. 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.

  4. Bayer-activities of daily living scale in mild and moderate dementia of the Alzheimer type.

    PubMed

    Nagaratnam, Nages; Nagaratnam, Kujan; O'Mara, Deborah

    2013-12-01

    The main purpose of this study is to examine the reliability of the Bayer-Activities of Daily Living (B-ADL) scale when used as a cognitive screening instrument for mild and moderate dementia of the Alzheimer type. This is a retrospective study of 66 patients with dementia. The B-ADL scale was completed by the caregiver or the family member at the first encounter. The internal consistency was found to be 0.94 for the 27 patients that completed all 25 questions in the scale. Significant correlation and receiver-operating characteristic curve analysis were found for the B-ADL total score and subscale 1 (tasks requiring short- and long-term memory) for Clinical Dementia Rating scale. Severity of dementia by the B-ADL scale is statistically similar but not the same as Mini-Mental State Examination. Our findings confirm that B-ADL scale is a valid indicator of the cognitive status of patients with Alzheimer's disease.

  5. 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),…

  6. 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...

  7. 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...

  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, 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...

  10. 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...

  11. Release probability of hippocampal glutamatergic terminals scales with the size of the active zone

    PubMed Central

    Holderith, Noemi; Lorincz, Andrea; Katona, Gergely; Rózsa, Balázs; Kulik, Akos; Watanabe, Masahiko; Nusser, Zoltan

    2012-01-01

    Cortical synapses display remarkable structural, molecular and functional heterogeneity. Our knowledge regarding the relationship between the ultrastructural and functional parameters is still fragmented. Here we asked how the release probability and presynaptic [Ca2+] transients relate to the ultrastructure of rat hippocampal glutamatergic axon terminals. Two-photon Ca2+ imaging-derived optical quantal analysis and correlated electron microscopic reconstructions revealed a tight correlation between the release probability and the active zone area. The peak amplitude of [Ca2+] transients in single boutons also positively correlated with the active zone area. Freeze-fracture immunogold labeling revealed that the voltage-gated Ca2+ channel subunit Cav2.1 and the presynaptic protein Rim1/2 are confined to the active zone and their numbers scale linearly with the active zone area. Gold particles for Cav2.1 showed a nonrandom distribution within the active zones. Our results demonstrate that the number of several active zone proteins, including presynaptic Ca2+ channels, docked vesicles and the release probability scales linearly with the active zone area. PMID:22683683

  12. Time-dependent restricted-active-space self-consistent-field theory for laser-driven many-electron dynamics. II. Extended formulation and numerical analysis

    NASA Astrophysics Data System (ADS)

    Miyagi, Haruhide; Madsen, Lars Bojer

    2014-06-01

    The time-dependent restricted-active-space self-consistent-field (TD-RASSCF) method is formulated based on the TD variational principle. The SCF based TD orbitals contributing to the expansion of the wave function are classified into three groups, between which orbital excitations are considered with the RAS scheme. In analogy with the configuration-interaction singles (CIS), singles-and-doubles (CISD), and singles-doubles-and-triples (CISDT) methods in quantum chemistry, the TD-RASSCF-S, -SD, and -SDT methods are introduced as extensions of the TD-RASSCF-doubles (-D) method [Phys. Rev. A 87, 062511 (2013), 10.1103/PhysRevA.87.062511]. Based on an analysis of the numerical cost and test calculations for one-dimensional (1D) models of atomic helium, beryllium, and carbon, it is shown that the TD-RASSCF-S and -D methods are computationally feasible for systems with many electrons and more accurate than the TD Hartree-Fock (TDHF) and TDCIS methods. In addition to the discussion of methodology, an analysis of electron dynamics in the high-order harmonic generation (HHG) process is presented. For the 1D beryllium atom, a state-resolved analysis of the HHG spectrum based on the time-independent HF orbitals shows that while only single-orbital excitations are needed in the region below the cutoff, single- and double-orbital excitations are essential beyond, where accordingly the single-active-electron (SAE) approximation and the TDCIS method break down. On the other hand, the TD-RASSCF-S and -D methods accurately describe the multiorbital excitation processes throughout the entire region of the HHG spectrum. For the 1D carbon atom, our calculations show that multiorbital excitations are essential in the HHG process even below the cutoff. Hence, in this test system a very accurate treatment of electron correlation is required. The TD-RASSCF-S and -D approaches meet this demand, while the SAE approximation and the TDCIS method are inadequate.

  13. Avoided crossings, conical intersections, and low-lying excited states with a single reference method: The restricted active space spin-flip configuration interaction approach

    NASA Astrophysics Data System (ADS)

    Casanova, David

    2012-08-01

    The restricted active space spin-flip CI (RASCI-SF) performance is tested in the electronic structure computation of the ground and the lowest electronically excited states in the presence of near-degeneracies. The feasibility of the method is demonstrated by analyzing the avoided crossing between the ionic and neutral singlet states of LiF along the molecular dissociation. The two potential energy surfaces (PESs) are explored by means of the energies of computed adiabatic and approximated diabatic states, dipole moments, and natural orbital electronic occupancies of both states. The RASCI-SF methodology is also used to study the ground and first excited singlet surface crossing involved in the double bond isomerization of ethylene, as a model case. The two-dimensional PESs of the ground (S0) and excited (S1) states are calculated for the complete configuration space of torsion and pyramidalization molecular distortions. The parameters that define the state energetics in the vicinity of the S0/S1 conical intersection region are compared to complete active space self-consistent field (CASSCF) results. These examples show that it is possible to describe strongly correlated electronic states using a single reference methodology without the need to expand the wavefunction to high levels of collective excitations. Finally, RASCI is also examined in the electronic structure characterization of the ground and 2^1{A}^-_g, 1^1{B}^+_u, 1^1{B}^-_u, and 1^3{B}^-_u states of all-trans polyenes with two to seven double bonds and beyond. Transition energies are compared to configuration interaction singles, time-dependent density functional theory (TDDFT), CASSCF, and its second-order perturbation correction calculations, and to experimental data. The capability of RASCI-SF to describe the nature and properties of each electronic state is discussed in detail. This example is also used to expose the properties of different truncations of the RASCI wavefunction and to show the

  14. 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

  15. 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

  16. 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.

  17. Psychometric Properties of the Scores on the Behavioral Inhibition and Activation Scales in a Sample of Norwegian Children

    ERIC Educational Resources Information Center

    Bjornebekk, Gunnar

    2009-01-01

    The primary aim of this study was to examine the psychometric properties of the scores on a version for children of the Carver and White Behavioral Inhibition and Activation scales (the BIS-BAS scales). This involved administering the BIS-BAS scales, the Positive and Negative Affect Schedule, the Junior Eysenck Personality Questionnaire…

  18. 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.

  19. 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.

  20. Measuring emotions during epistemic activities: the Epistemically-Related Emotion Scales.

    PubMed

    Pekrun, Reinhard; Vogl, Elisabeth; Muis, Krista R; Sinatra, Gale M

    2016-07-22

    Measurement instruments assessing multiple emotions during epistemic activities are largely lacking. We describe the construction and validation of the Epistemically-Related Emotion Scales, which measure surprise, curiosity, enjoyment, confusion, anxiety, frustration, and boredom occurring during epistemic cognitive activities. The instrument was tested in a multinational study of emotions during learning from conflicting texts (N = 438 university students from the United States, Canada, and Germany). The findings document the reliability, internal validity, and external validity of the instrument. A seven-factor model best fit the data, suggesting that epistemically-related emotions should be conceptualised in terms of discrete emotion categories, and the scales showed metric invariance across the North American and German samples. Furthermore, emotion scores changed over time as a function of conflicting task information and related significantly to perceived task value and use of cognitive and metacognitive learning strategies.

  1. 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

  2. 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.

  3. Activation barrier scaling and crossover for noise-induced switching in micromechanical parametric oscillators.

    PubMed

    Chan, H B; Stambaugh, C

    2007-08-10

    We explore fluctuation-induced switching in parametrically driven micromechanical torsional oscillators. The oscillators possess one, two, or three stable attractors depending on the modulation frequency. Noise induces transitions between the coexisting attractors. Near the bifurcation points, the activation barriers are found to have a power law dependence on frequency detuning with critical exponents that are in agreement with predicted universal scaling relationships. At large detuning, we observe a crossover to a different power law dependence with an exponent that is device specific.

  4. Active region 11748: Recurring X-class flares, large scale dimmings and waves.

    NASA Astrophysics Data System (ADS)

    Davey, Alisdair R.; Malanushenko, Anna; McIntosh, Scott W.

    2014-06-01

    AR 11748 was a relatively compact active region that crossed the solar disk between 05/14/2013 and 05/26/2013. Despite its size it produced a number X-class flares, and global scale eruptive events that were captured by the SDO Feature Finding Team's (FFT) Dimming Region Detector. Using the results of this module and other FFT modules, we present an analysis of the this AR region and investigate why it was so globally impactful.

  5. 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

  6. [Changes in endothelium-dependent dilation and α1-adrenoreactivity of rat aorta caused by inducible NO-synthase inhibition after motor activity restrictions].

    PubMed

    Solodkov, A P; Iatskovskaia, N M

    2013-07-01

    The aim of work was to study the influence of the highly selective blocker of the inducible NO-synthase (iNOS) of S-methylthiourea on the alteration of the endothelium-dependent vasodilation and α1-adrenoreactivity of the isolated rat aortic rings which underwent a short-term restriction of physical activity. The experiments were carried out on rat aortic rings preparations from female-rats bathed in Krebs-Henseleit solution, bubbled with 95% O2 and 5% CO2 and contracting in isometric mode. Endothelium-dependent dilation was caused by cumulative addition of acetylcholine (10-(10)-10(-4) M) after phenylephrine precontraction(10(-6) M). Adrenoreactivity was assessed through the response to increasing concentrations of α1-adrenergic receptor agonist. The 60-minute immobilization stress, characterized by the increase of the relative weight of the adrenal glands by 19.5%, the concentration of glucocorticoids (twice as much), of NO2/NO3 (stable NO degradation products) by 35%, the reduction in the level of thyroxine (by 16%), triiodothyronine (by 10%) and the increase in thyrotropic hormone by 45%, interleukin-1b (twice as much) and the appearance of tumour necrosis factor alpha in the blood serum, was accompanied by the two types of reaction of isolated aortic rings to acetylcholine and phenylephrine. The first one was expressed in the enhancing of acetylcholine-induced dilation of isolated aortic rings and the reduction of its response to α1-adrenergic stimulant phenylephrine. The second one showed a decrease in the response of isolated aortic rings to acetylcholine and enhancing the response to phenylephrine. But both of these reaction types were eliminated by using highly selective inducible NO-synthase inhibitor with S-methylisothiourea. However, it was differently directed with a different type of reaction. Taken together, these results suggest that the iNOS is formed in the cells of rat aorta under short-term stress. In some cases it can be a source of a large

  7. Properties of pyrolytic chars and activated carbons derived from pilot-scale pyrolysis of used tires.

    PubMed

    Li, S Q; Yao, Q; Wen, S E; Chi, Y; Yan, J H

    2005-09-01

    Used tires were pyrolyzed in a pilot-scale quasi-inert rotary kiln. Influences of variables, such as time, temperature, and agent flow, on the activation of obtained char were subsequently investigated in a laboratory-scale fixed bed. Mesoporous pores are found to be dominant in the pore structures of raw char. Brunauer-Emmett-Teller (BET) surfaces of activated chars increased linearly with carbon burnoff. The carbon burnoff of tire char achieved by carbon dioxide (CO2) under otherwise identical conditions was on average 75% of that achieved by steam, but their BET surfaces are almost the same. The proper activation greatly improved the aqueous adsorption of raw char, especially for small molecular adsorbates, for example, phenol from 6 to 51 mg/g. With increasing burnoff, phenol adsorption exhibited a first-stage linear increase followed by a rapid drop after 30% burnoff. Similarly, iodine adsorption first increased linearly, but it held as the burnoff exceeded 40%, which implied that the reduction of iodine adsorption due to decreasing micropores was partially made up by increasing mesopores. Both raw chars and activated chars showed appreciable adsorption capacity of methylene-blue comparable with that of commercial carbons. Thus, tire-derived activated carbons can be used as an excellent mesoporous adsorbent for larger molecular species.

  8. 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

  9. 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

  10. 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

  11. OBSERVING EVOLUTION IN THE SUPERGRANULAR NETWORK LENGTH SCALE DURING PERIODS OF LOW SOLAR ACTIVITY

    SciTech Connect

    McIntosh, Scott W.; Rast, Mark P.; Leamon, Robert J.; Hock, Rachel A.; Ulrich, Roger K.

    2011-03-20

    We present the initial results of an observational study into the variation of the dominant length scale of quiet solar emission: supergranulation. The distribution of magnetic elements in the lanes that from the network affects, and reflects, the radiative energy in the plasma of the upper solar chromosphere and transition region at the magnetic network boundaries forming as a result of the relentless interaction of magnetic fields and convective motions of the Suns' interior. We demonstrate that a net difference of {approx}0.5 Mm in the supergranular emission length scale occurs when comparing observation cycle 22/23 and cycle 23/24 minima. This variation in scale is reproduced in the data sets of multiple space- and ground-based instruments and using different diagnostic measures. By means of extension, we consider the variation of the supergranular length scale over multiple solar minima by analyzing a subset of the Mount Wilson Solar Observatory Ca II K image record. The observations and analysis presented provide a tantalizing look at solar activity in the absence of large-scale flux emergence, offering insight into times of 'extreme' solar minimum and general behavior such as the phasing and cross-dependence of different components of the spectral irradiance. Given that the modulation of the supergranular scale imprints itself in variations of the Suns' spectral irradiance, as well as in the mass and energy transport into the entire outer atmosphere, this preliminary investigation is an important step in understanding the impact of the quiet Sun on the heliospheric system.

  12. Observing Evolution in the Supergranular Network Length Scale During Periods of Low Solar Activity

    NASA Astrophysics Data System (ADS)

    McIntosh, Scott W.; Leamon, Robert J.; Hock, Rachel A.; Rast, Mark P.; Ulrich, Roger K.

    2011-03-01

    We present the initial results of an observational study into the variation of the dominant length scale of quiet solar emission: supergranulation. The distribution of magnetic elements in the lanes that from the network affects, and reflects, the radiative energy in the plasma of the upper solar chromosphere and transition region at the magnetic network boundaries forming as a result of the relentless interaction of magnetic fields and convective motions of the Suns' interior. We demonstrate that a net difference of ~0.5 Mm in the supergranular emission length scale occurs when comparing observation cycle 22/23 and cycle 23/24 minima. This variation in scale is reproduced in the data sets of multiple space- and ground-based instruments and using different diagnostic measures. By means of extension, we consider the variation of the supergranular length scale over multiple solar minima by analyzing a subset of the Mount Wilson Solar Observatory Ca II K image record. The observations and analysis presented provide a tantalizing look at solar activity in the absence of large-scale flux emergence, offering insight into times of "extreme" solar minimum and general behavior such as the phasing and cross-dependence of different components of the spectral irradiance. Given that the modulation of the supergranular scale imprints itself in variations of the Suns' spectral irradiance, as well as in the mass and energy transport into the entire outer atmosphere, this preliminary investigation is an important step in understanding the impact of the quiet Sun on the heliospheric system.

  13. Type II restriction endonuclease R.Hpy188I belongs to the GIY-YIG nuclease superfamily, but exhibits an unusual active site

    PubMed Central

    Kaminska, Katarzyna H; Kawai, Mikihiko; Boniecki, Michal; Kobayashi, Ichizo; Bujnicki, Janusz M

    2008-01-01

    Background Catalytic domains of Type II restriction endonucleases (REases) belong to a few unrelated three-dimensional folds. While the PD-(D/E)XK fold is most common among these enzymes, crystal structures have been also determined for single representatives of two other folds: PLD (R.BfiI) and half-pipe (R.PabI). Bioinformatics analyses supported by mutagenesis experiments suggested that some REases belong to the HNH fold (e.g. R.KpnI), and that a small group represented by R.Eco29kI belongs to the GIY-YIG fold. However, for a large fraction of REases with known sequences, the three-dimensional fold and the architecture of the active site remain unknown, mostly due to extreme sequence divergence that hampers detection of homology to enzymes with known folds. Results R.Hpy188I is a Type II REase with unknown structure. PSI-BLAST searches of the non-redundant protein sequence database reveal only 1 homolog (R.HpyF17I, with nearly identical amino acid sequence and the same DNA sequence specificity). Standard application of state-of-the-art protein fold-recognition methods failed to predict the relationship of R.Hpy188I to proteins with known structure or to other protein families. In order to increase the amount of evolutionary information in the multiple sequence alignment, we have expanded our sequence database searches to include sequences from metagenomics projects. This search resulted in identification of 23 further members of R.Hpy188I family, both from metagenomics and the non-redundant database. Moreover, fold-recognition analysis of the extended R.Hpy188I family revealed its relationship to the GIY-YIG domain and allowed for computational modeling of the R.Hpy188I structure. Analysis of the R.Hpy188I model in the light of sequence conservation among its homologs revealed an unusual variant of the active site, in which the typical Tyr residue of the YIG half-motif had been substituted by a Lys residue. Moreover, some of its homologs have the otherwise

  14. Psychometric properties of the Physical Activity Scale for the Elderly in Chinese patients with COPD

    PubMed Central

    Tao, Yan-xia; Wang, Lan; Dong, Xiao-yan; Zheng, Hong; Zheng, Ya-shu; Tang, Xing-yue; Zhao, Yue; Zhang, Qing

    2017-01-01

    Background For patients with COPD, physical activity (PA) is recommended as the core component of pulmonary rehabilitation, but there is lack of a validated questionnaire for assessing the PA effectively. Aim To evaluate the reliability and validity of the Chinese version of Physical Activity Scale for the Elderly (PASE-C) in patients with COPD. Methods A cross-sectional study was conducted with 167 outpatients aged 60 years or older with COPD. Test−retest reliability and internal consistency were calculated by intraclass correlation coefficient (ICC) and Cronbach’s coefficient α, respectively. Validity was evaluated by correlation with the International Physical Activity Questionnaire-Short (IPAQ-S), data of pedometer, Self-Efficacy for Managing Chronic Disease 6-Item Scale (SES6), Hospital Anxiety and Depression Scale (HADS), Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), grip strength, and disease characteristics. Results The PASE-C had an excellent seven-day test−retest reliability (ICC=0.98) and an acceptable internal consistency (Cronbach’s α=0.71). The content validity was supported by an item-content validity index, a scale-content validity index/universal agreement, and a scale-content validity index/average value of 0.70–1, 0.70, and 0.93, respectively. Concurrent validity was tested by correlation with IPAQ-S (r=0.651). Criterion validity was confirmed by correlation with the walking steps (r=0.611) and energy expenditure (r=0.493). For construct validity, PASE-C had correlations with SES6 (r=0.396), HADS for depression (r=−0.234), seven subscales of SF-36 (r=0.182–0.525), grip strength (r=0.341), and disease characteristics including the duration of COPD (r=−0.215), modified British Medical Research Council scale (r=−0.354), forced expiratory volume in one second as percentage of predicted (r=0.307), and Global Initiative for Chronic Obstructive Lung Disease grade (r=−0.264), with a good construct validity (all P

  15. Energy restriction and potential energy restriction mimetics.

    PubMed

    Nikolai, Sibylle; Pallauf, Kathrin; Huebbe, Patricia; Rimbach, Gerald

    2015-12-01

    Energy restriction (ER; also known as caloric restriction) is the only nutritional intervention that has repeatedly been shown to increase lifespan in model organisms and may delay ageing in humans. In the present review we discuss current scientific literature on ER and its molecular, metabolic and hormonal effects. Moreover, criteria for the classification of substances that might induce positive ER-like changes without having to reduce energy intake are summarised. Additionally, the putative ER mimetics (ERM) 2-deoxy-d-glucose, metformin, rapamycin, resveratrol, spermidine and lipoic acid and their suggested molecular targets are discussed. While there are reports on these ERM candidates that describe lifespan extension in model organisms, data on longevity-inducing effects in higher organisms such as mice remain controversial or are missing. Furthermore, some of these candidates produce detrimental side effects such as immunosuppression or lactic acidosis, or have not been tested for safety in long-term studies. Up to now, there are no known ERM that could be recommended without limitations for use in humans.

  16. 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.

  17. Standardized training tools for the UPDRS activities of daily living scale: newly available teaching program.

    PubMed

    Goetz, Christopher G; LeWitt, Peter A; Weidenman, Meredith

    2003-12-01

    The Unified Parkinson's Disease Rating Scale (UPDRS) is the most widely used scale for evaluation of clinical impairment in PD. Whereas the motor section has been studied intensively for clinimetric properties and has an associated training tape, the Activities of Daily Living (ADL) section has been studied less rigorously. In preparation for a multicenter study that planned to use the UPDRS ADL score as an outcome, the authors reviewed the UPDRS ADL scale and designed a teaching program to provide a uniform technique for data acquisition without changing any wording of the primary scale. The teaching program is composed of four components: overall guidelines, clarifying points, recommended strategies, and a teaching videotape. The videotape shows examples of interviewers assessing each ADL item with patients of different disability levels and provides a complete ADL assessment of a single patient. Systematic training and utilization of this teaching program offer the potential for more uniformity in results of ADL assessments conducted in clinical practice and multicenter, international studies of PD. The written materials and videotape belong to the Movement Disorder Society and are available by contacting the MDS central office.

  18. 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

  19. 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

  20. Antibacterial and enzymatic activity of microbial community during wastewater treatment by pilot scale vermifiltration system.

    PubMed

    Arora, Sudipti; Rajpal, Ankur; Bhargava, Renu; Pruthi, Vikas; Bhatia, Akansha; Kazmi, A A

    2014-08-01

    The present study investigated microbial community diversity and antibacterial and enzymatic properties of microorganisms in a pilot-scale vermifiltration system during domestic wastewater treatment. The study included isolation and identification of diverse microbial community by culture-dependent method from a vermifilter (VF) with earthworms and a conventional geofilter (GF) without earthworms. The results of the four months study revealed that presence of earthworms in VF could efficiently remove biochemical oxygen demand (BOD), chemical oxygen demand (COD), total and fecal coliforms, fecal streptococci and other pathogens. Furthermore, the burrowing activity of earthworms promoted the aeration conditions in VF which led to the predominance of the aerobic microorganisms, accounting for complex microbial community diversity. Antibacterial activity of the isolated microorganisms revealed the mechanism behind the removal of pathogens, which is reported for the first time. Specifically, cellulase, amylase and protease activity is responsible for biodegradation and stabilization of organic matter.

  1. Restriction/modification polypeptides, polynucleotides, and methods

    DOEpatents

    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.

  2. Short Promoters in Viral Vectors Drive Selective Expression in Mammalian Inhibitory Neurons, but do not Restrict Activity to Specific Inhibitory Cell-Types

    PubMed Central

    Nathanson, Jason L.; Jappelli, Roberto; Scheeff, Eric D.; Manning, Gerard; Obata, Kunihiko; Brenner, Sydney; Callaway, Edward M.

    2009-01-01

    Short cell-type specific promoter sequences are important for targeted gene therapy and studies of brain circuitry. We report on the ability of short promoter sequences to drive fluorescent protein expression in specific types of mammalian cortical inhibitory neurons using adeno-associated virus (AAV) and lentivirus (LV) vectors. We tested many gene regulatory sequences derived from fugu (Takifugu rubripes), mouse, human, and synthetic composite regulatory elements. All fugu compact promoters expressed in mouse cortex, with only the somatostatin (SST) and the neuropeptide Y (NPY) promoters largely restricting expression to GABAergic neurons. However these promoters did not control expression in inhibitory cells in a subtype specific manner. We also tested mammalian promoter sequences derived from genes putatively coexpressed or coregulated within three major inhibitory interneuron classes (PV, SST, VIP). In contrast to the fugu promoters, many of the mammalian sequences failed to express, and only the promoter from gene A930038C07Rik conferred restricted expression, although as in the case of the fugu sequences, this too was not inhibitory neuron subtype specific. Lastly and more promisingly, a synthetic sequence consisting of a composite regulatory element assembled with PAX6 E1.1 binding sites, NRSE and a minimal CMV promoter showed markedly restricted expression to a small subset of mostly inhibitory neurons, but whose commonalities are unknown. PMID:19949461

  3. 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.

  4. The Pressure-Activation-Stress scale in relation to ADHD and cortisol.

    PubMed

    Isaksson, J; Nilsson, K W; Lindblad, F

    2015-02-01

    The Pressure-Activation-Stress (PAS) scale is a self-report questionnaire for children concerning perceived stress. To explore behavioral and physiological correlates, we investigated if scores discriminate between a group prone to perceive high levels of stress [children with attention-deficit/hyperactivity disorder (ADHD)] and a healthy school sample, and if they are associated with diurnal cortisol levels. The PAS scale was filled in at home by children (11-17 years) with clinically confirmed ADHD (n = 102) and non-affected comparisons (n = 146). Saliva samples were collected four times during a regular school day for radioimmunoassay analysis of cortisol. Subtypes and severity of ADHD symptoms were determined using parental rating scales. Children with ADHD scored higher on the PAS scale than a school sample. The PAS scores were similar over ages in the ADHD group while they increased with age in the healthy group. Female sex was associated with higher stress in both groups but no gender interaction was found. No association was found between PAS scores and cortisol levels in neither group. Children in the ADHD group had a lower ratio of cortisol levels/perceived stress on all sampling occasions, built up both by the higher PAS scores and the lower cortisol levels in children with ADHD. The higher PAS scores in children with ADHD support the validity of the scale. The lack of association between PAS scores and diurnal cortisol levels is intriguing and illustrates the complexity of the stress concept. Stress-related fragility seems to accompany ADHD during childhood.

  5. Verapamil hepatic clearance in four preclinical rat models: towards activity-based scaling.

    PubMed

    Nicolaï, J; De Bruyn, T; Van Veldhoven, P P; Keemink, J; Augustijns, P; Annaert, P

    2015-10-01

    The current study was designed to cross-validate rat liver microsomes (RLM), suspended rat hepatocytes (SRH) and the isolated perfused rat liver (IPRL) model against in vivo pharmacokinetic data, using verapamil as a model drug. Michaelis-Menten constants (Km), for the metabolic disappearance kinetics of verapamil in RLM and SRH (freshly isolated and cryopreserved), were determined and corrected for non-specific binding. The 'unbound' Km determined with RLM (2.8 µM) was divided by the 'unbound' Km determined with fresh and cryopreserved SRH (3.9 µM and 2.1 µM, respectively) to calculate the ratio of intracellular to extracellular unbound concentration (Kpu,u). Kpu,u was significantly different between freshly isolated (0.71) and cryopreserved (1.31) SRH, but intracellular capacity for verapamil metabolism was maintained after cryopreservation (200 vs. 191 µl/min/million cells). Direct comparison of intrinsic clearance values (Clint) in RLM versus SRH, yielded an activity-based scaling factor (SF) of 0.28-0.30 mg microsomal protein/million cells (MPPMC). Merging the IPRL-derived Clint with the MPPMC and SRH data, resulted in scaling factors for MPPGL (80 and 43 mg microsomal protein/g liver) and HPGL (269 and 153 million cells/g liver), respectively. Likewise, the hepatic blood flow (61 ml/min/kg b.wt) was calculated using IPRL Clint and the in vivo Cl. The scaling factors determined here are consistent with previously reported CYP450-content based scaling factors. Overall, the results show that integrated interpretation of data obtained with multiple preclinical tools (i.e. RLM, SRH, IPRL) can contribute to more reliable estimates for scaling factors and ultimately to improved in vivo clearance predictions based on in vitro experimentation.

  6. 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.

  7. Delineation of Urban Active Faults Using Multi-scale Gravity Analysis in Shenzhen, South China

    NASA Astrophysics Data System (ADS)

    Xu, C.; Liu, X.

    2015-12-01

    In fact, many cities in the world are established on the active faults. As the rapid urban development, thousands of large facilities, such as ultrahigh buildings, supersized bridges, railway, and so on, are built near or on the faults, which may change the balance of faults and induce urban earthquake. Therefore, it is significant to delineate effectively the faults for urban planning construction and social sustainable development. Due to dense buildings in urban area, the ordinary approaches to identify active faults, like geological survey, artificial seismic exploration and electromagnetic exploration, are not convenient to be carried out. Gravity, reflecting the mass distribution of the Earth's interior, provides a more efficient and convenient method to delineate urban faults. The present study is an attempt to propose a novel gravity method, multi-scale gravity analysis, for identifying urban active faults and determining their stability. Firstly, the gravity anomalies are decomposed by wavelet multi-scale analysis. Secondly, based on the decomposed gravity anomalies, the crust is layered and the multilayer horizontal tectonic stress is inverted. Lastly, the decomposed anomalies and the inverted horizontal tectonic stress are used to infer the distribution and stability of main active faults. For validating our method, a case study on active faults in Shenzhen City is processed. The results show that the distribution of decomposed gravity anomalies and multilayer horizontal tectonic stress are controlled significantly by the strike of the main faults and can be used to infer depths of the faults. The main faults in Shenzhen may range from 4km to 20km in the depth. Each layer of the crust is nearly equipressure since the horizontal tectonic stress has small amplitude. It indicates that the main faults in Shenzhen are relatively stable and have no serious impact on planning and construction of the city.

  8. Evaluation of An Activities of Daily Living Scale for Adolescents and Adults with Developmental Disabilities

    PubMed Central

    Maenner, Matthew J; Smith, Leann E; Hong, Jinkuk; Makuch, Renee; Greenberg, Jan S; Mailick, Marsha R

    2012-01-01

    Background Activity limitations are an important and useful dimension of disability, but there are few validated measures of activity limitations for adolescents and adults with developmental disabilities. Objective/Hypothesis To describe the development of the Waisman Activities of Daily Living (W-ADL) Scale for adolescents and adults with developmental disabilities, and systematically evaluate its measurement properties according to an established set of criteria. Methods The W-ADL was administered among four longitudinally-studied groups of adolescents and adults with developmental disabilities: 406 with autism; 147 with fragile-X syndrome; 169 with Down syndrome, and 292 with intellectual disability of other or unknown origin. The W-ADL contains 17 activities and each is rated on a 3-point scale (0=“does not do at all”, 1=“does with help”, 2=“independent”), and a standard set of criteria were used to evaluate its measurement properties. Results Across the disability groups, Cronbach’s alphas ranged from 0.88 to 0.94, and a single-factor structure was most parsimonious. The W-ADL was reliable over time, with weighted kappas between 0.92 and 0.93. Criterion and construct validity were supported through substantial associations with the Vineland Screener, need for respite services, caregiving burden, and competitive employment. No floor or ceiling effects were present. There were significant group differences in W-ADL scores by maternally-reported level of intellectual disability (mild, moderate, severe, profound). Conclusions The W-ADL exceeded the recommended threshold for each quality criterion the authors evaluated. This freely-available tool is an efficient measure of activities of daily living for surveys and epidemiological research concerning adolescents and adults with developmental disabilities. PMID:23260606

  9. 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.

  10. Perioperative Fluid Restriction

    PubMed Central

    Bleier, Joshua I.S.; Aarons, Cary B.

    2013-01-01

    Perioperative fluid management of the colorectal surgical patient has evolved significantly over the last five decades. Older notions espousing aggressive hydration have been shown to be associated with increased complications. Newer data regarding fluid restriction has shown an association with improved outcomes. Management of perioperative fluid administration can be considered in three primary phases: In the preoperative phase, data suggests that avoidance of preoperative bowel preparation and avoidance of undue preoperative dehydration can improve outcomes. Although the type of intraoperative fluid given does not have a significant effect on outcome, data do suggest that a restrictive fluid regimen results in improved outcomes. Finally, in the postoperative phase of fluid management, a fluid-restrictive regimen, coupled with early enteral feeding also seems to result in improved outcomes. PMID:24436675

  11. Activation volume of selected liquid crystals in the density scaling regime

    NASA Astrophysics Data System (ADS)

    Grzybowski, A.; Urban, S.; Mroz, S.; Paluch, M.

    2017-02-01

    In this paper, we demonstrate and thoroughly analyze the activation volumetric properties of selected liquid crystals in the nematic and crystalline E phases in comparison with those reported for glass-forming liquids. In the analysis, we have employed and evaluated two entropic models (based on either total or configurational entropies) to describe the longitudinal relaxation times of the liquid crystals in the density scaling regime. In this study, we have also exploited two equations of state: volumetric and activation volumetric ones. As a result, we have established that the activation volumetric properties of the selected liquid crystals are quite opposite to such typical properties of glass-forming materials, i.e., the activation volume decreases and the isothermal bulk modulus increases when a liquid crystal is isothermally compressed. Using the model based on the configurational entropy, we suggest that the increasing pressure dependences of the activation volume in isothermal conditions and the negative curvature of the pressure dependences of isothermal longitudinal relaxation times can be related to the formation of antiparallel doublets in the examined liquid crystals. A similar pressure effect on relaxation dynamics may be also observed for other material groups in case of systems, the molecules of which form some supramolecular structures.

  12. Activation volume of selected liquid crystals in the density scaling regime

    PubMed Central

    Grzybowski, A.; Urban, S.; Mroz, S.; Paluch, M.

    2017-01-01

    In this paper, we demonstrate and thoroughly analyze the activation volumetric properties of selected liquid crystals in the nematic and crystalline E phases in comparison with those reported for glass-forming liquids. In the analysis, we have employed and evaluated two entropic models (based on either total or configurational entropies) to describe the longitudinal relaxation times of the liquid crystals in the density scaling regime. In this study, we have also exploited two equations of state: volumetric and activation volumetric ones. As a result, we have established that the activation volumetric properties of the selected liquid crystals are quite opposite to such typical properties of glass-forming materials, i.e., the activation volume decreases and the isothermal bulk modulus increases when a liquid crystal is isothermally compressed. Using the model based on the configurational entropy, we suggest that the increasing pressure dependences of the activation volume in isothermal conditions and the negative curvature of the pressure dependences of isothermal longitudinal relaxation times can be related to the formation of antiparallel doublets in the examined liquid crystals. A similar pressure effect on relaxation dynamics may be also observed for other material groups in case of systems, the molecules of which form some supramolecular structures. PMID:28181530

  13. Signatures of large-scale magnetic fields in active galactic nuclei jets: transverse asymmetries

    NASA Astrophysics Data System (ADS)

    Clausen-Brown, E.; Lyutikov, M.; Kharb, P.

    2011-08-01

    We investigate the emission properties that a large-scale helical magnetic field imprints on active galactic nuclei (AGN) jet synchrotron radiation. A cylindrically symmetric relativistic jet and large-scale helical magnetic field produce significant asymmetrical features in transverse profiles of fractional linear polarization, intensity, the Faraday rotation and spectral index. The asymmetrical features of these transverse profiles correlate with one another in ways specified by the handedness of the helical field, the jet viewing angle (θob) and the bulk Lorentz factor of the flow (Γ). Thus, these correlations may be used to determine the structure of the magnetic field in the jet. In the case of radio galaxies (θob˜ 1 rad) and a subclass of blazars with particularly small viewing angles (θob≪ 1/Γ), we find an edge-brightened intensity profile that is similar to that observed in the radio galaxy M87. We present observations of the AGNs 3C 78 and NRAO 140 that display the type of transverse asymmetries that may be produced by large-scale helical magnetic fields.

  14. Active self-testing noise measurement sensors for large-scale environmental sensor networks.

    PubMed

    Domínguez, Federico; Cuong, Nguyen The; Reinoso, Felipe; Touhafi, Abdellah; Steenhaut, Kris

    2013-12-13

    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.

  15. 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

  16. 7 CFR 1710.125 - Restrictions on lobbying.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 11 2010-01-01 2010-01-01 false Restrictions on lobbying. 1710.125 Section 1710.125... 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....

  17. 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...

  18. 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

  19. Miniature microscopes for large-scale imaging of neuronal activity in freely behaving rodents.

    PubMed

    Ziv, Yaniv; Ghosh, Kunal K

    2015-06-01

    Recording neuronal activity in behaving subjects has been instrumental in studying how information is represented and processed by the brain. Recent advances in optical imaging and bioengineering have converged to enable time-lapse, cell-type specific recordings of neuronal activities from large neuronal populations in deep-brain structures of freely behaving rodents. We will highlight these advancements, with an emphasis on miniaturized integrated microscopy for large-scale imaging in freely behaving mice. This technology potentially enables studies that were difficult to perform using previous generation imaging and current electrophysiological techniques. These studies include longitudinal and population-level analyses of neuronal representations associated with different types of naturalistic behaviors and cognitive or emotional processes.

  20. 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.

  1. 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.

  2. 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…

  3. Restriction map of the 125-kilobase plasmid of Bacillus thuringiensis subsp. israelensis carrying the genes that encode delta-endotoxins active against mosquito larvae.

    PubMed Central

    Ben-Dov, E; Einav, M; Peleg, N; Boussiba, S; Zaritsky, A

    1996-01-01

    A large plasmid containing all delta-endotoxin genes was isolated from Bacillus thuringiensis subsp. israelensis; restricted by BamHI, EcoRI, HindIII, KpnI, PstI, SacI, and SalI; and cloned as appropriate libraries in Escherichia coli. The libraries were screened for inserts containing recognition sites for BamHI, SacI, and SalI. Each was labeled with 32P and hybridized to Southern blots of gels with fragments generated by cleaving the plasmid with several restriction endonucleases, to align at least two fragments of the relevant enzymes. All nine BamHI fragments and all eight SacI fragments were mapped in two overlapping linkage groups (with total sizes of about 76 and 56 kb, respectively). The homology observed between some fragments is apparently a consequence of the presence of transposons and repeated insertion sequences. Four delta-endotoxin genes (cryIVB-D and cytA) and two genes for regulatory polypeptides (of 19 and 20 kDa) were localized on a 21-kb stretch of the plasmid; without cytA, they are placed on a single BamHI fragment. This convergence enables subcloning of delta-endotoxin genes (excluding cryIVA, localized on the other linkage group) as an intact natural fragment. PMID:8795201

  4. Restricting Grammatical Complexity

    ERIC Educational Resources Information Center

    Frank, Robert

    2004-01-01

    Theories of natural language syntax often characterize grammatical knowledge as a form of abstract computation. This paper argues that such a characterization is correct, and that fundamental properties of grammar can and should be understood in terms of restrictions on the complexity of possible grammatical computation, when defined in terms of…

  5. Using active colloids as machines to weave and braid on the micrometer scale

    NASA Astrophysics Data System (ADS)

    Goodrich, Carl P.; Brenner, Michael P.

    2017-01-01

    Controlling motion at the microscopic scale is a fundamental goal in the development of biologically inspired systems. We show that the motion of active, self-propelled colloids can be sufficiently controlled for use as a tool to assemble complex structures such as braids and weaves out of microscopic filaments. Unlike typical self-assembly paradigms, these structures are held together by geometric constraints rather than adhesive bonds. The out-of-equilibrium assembly that we propose involves precisely controlling the 2D motion of active colloids so that their path has a nontrivial topology. We demonstrate with proof-of-principle Brownian dynamics simulations that, when the colloids are attached to long semiflexible filaments, this motion causes the filaments to braid. The ability of the active particles to provide sufficient force necessary to bend the filaments into a braid depends on a number of factors, including the self-propulsion mechanism, the properties of the filament, and the maximum curvature in the braid. Our work demonstrates that nonequilibrium assembly pathways can be designed using active particles.

  6. Observational Evidence for Active Galactic Nuclei Feedback at the Parsec Scale

    NASA Astrophysics Data System (ADS)

    Yuan, Feng; Li, Miao

    2011-08-01

    In a hot accretion flow, the radiation from the innermost region of the flow propagates outward and heats the electrons at large radii via Compton scattering. It has been shown in previous works that if the radiation is strong enough, L >~ 2%L Edd, the electrons at the Bondi radius (rB ~ 105 rs ) will be heated to above the virial temperature; thus, the accretion will be stopped. The accretion will recover after the gas cools down. This results in the oscillation of the black hole activity. In this paper, we show that this mechanism is the origin of the intermittent activity of some compact young radio sources. Such intermittency is required to explain the population of these sources. We calculate the timescales of the black hole oscillation and find that the durations of active and inactive phases are 3 × 104(0.1/α)(M/108 M sun)(L/2%L Edd)-1/2 yr and 105(α/0.1)(M/108 M sun) yr, respectively, consistent with those required to explain observations. Such feedback occurring at the parsec scale should be common in low-luminosity active galactic nuclei and should be considered when we consider their matter and energy output.

  7. Macro optical projection tomography for large scale 3D imaging of plant structures and gene activity.

    PubMed

    Lee, Karen J I; Calder, Grant M; Hindle, Christopher R; Newman, Jacob L; Robinson, Simon N; Avondo, Jerome J H Y; Coen, Enrico S

    2016-12-26

    Optical projection tomography (OPT) is a well-established method for visualising gene activity in plants and animals. However, a limitation of conventional OPT is that the specimen upper size limit precludes its application to larger structures. To address this problem we constructed a macro version called Macro OPT (M-OPT). We apply M-OPT to 3D live imaging of gene activity in growing whole plants and to visualise structural morphology in large optically cleared plant and insect specimens up to 60 mm tall and 45 mm deep. We also show how M-OPT can be used to image gene expression domains in 3D within fixed tissue and to visualise gene activity in 3D in clones of growing young whole Arabidopsis plants. A further application of M-OPT is to visualise plant-insect interactions. Thus M-OPT provides an effective 3D imaging platform that allows the study of gene activity, internal plant structures and plant-insect interactions at a macroscopic scale.

  8. Small-scale and large-scale testing of photo-electrochemically activated leaching technology in Aprelkovo and Delmachik Mines

    NASA Astrophysics Data System (ADS)

    Sekisov, AG; Lavrov, AYu; Rubtsov, YuI

    2017-02-01

    The paper gives a description of tests and trials of the technology of heap gold leaching from rebellious ore in Aprelkovo and Delmachik Mines. Efficiency of leaching flowsheets with the stage-wise use of activated solutions of different reagents, including active forms of oxygen, is evaluated. Carbonate–peroxide solutions are used at the first stage of leaching to oxidize sulfide and sulfide–arsenide ore minerals to recover iron and copper from them. The second stage leaching uses active cyanide solutions to leach encapsulated and disperse gold and silver.

  9. 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.

  10. A new vegetation model at the topographic scale in Mongolia under human activity and climate change

    NASA Astrophysics Data System (ADS)

    Ishii, R.; Matsuoka, M.; Fujita, N.

    2013-12-01

    To predict future vegetation not only the changes in climate conditions but those of essential human activities must also be incorporated in a vegetation model, since most terrestrial systems are now under the strong influence of both of these drivers. Previous dynamic vegetation models, however, had difficulties to incorporate these effects in a comparative way and one of the critical barrier was the mismatch of the spatial scales at which both of these drivers are quantified, that is, climate conditions are generally observed and modeled with much coarser resolutions than human activities often influenced by topography or transportation networks. In northern part of Mongolia, where plant growth is basically limited by water availability and grazing pressure by livestock, the vegetation exhibits a clear discontinuous transition between grassland and forest but no sound modeling could be achieved to clarify the transition mechanisms nor to project future vegetation and hence the distribution of ecosystem functions. To tackle this problem, we developed a pair of new models at the topographic scale (Models 1&2) based on the observation in a sample region in Mongolia. Model 1 is a mathematical model for the dynamic interactions among the two plant biomasses (grass and trees) and local soil water content (SWC). We here assume positive/negative feedbacks in plant growth-SWC interaction and uneven grazing pressures for the two plants. Model 2 estimates numerically the spatial distribution of the potential SWC governed by climate and topography conditions in a given region. We used satellite remote sensing data to obtain the spatial distributions of the initial vegetation cover and the topography. By integrating these two models we could successfully reconstruct the current spatial vegetation patterns in our sample area only when we assumed a strong positive feedback in plant growth-SWC interaction and grazing pressure. This result underscores the importance of the

  11. 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

  12. 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

    2014-07-07

    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

  13. Restricted sample variance reduces generalizability.

    PubMed

    Lakes, Kimberley D

    2013-06-01

    One factor that affects the reliability of observed scores is restriction of range on the construct measured for a particular group of study participants. This study illustrates how researchers can use generalizability theory to evaluate the impact of restriction of range in particular sample characteristics on the generalizability of test scores and to estimate how changes in measurement design could improve the generalizability of the test scores. An observer-rated measure of child self-regulation (Response to Challenge Scale; Lakes, 2011) is used to examine scores for 198 children (Grades K through 5) within the generalizability theory (GT) framework. The generalizability of ratings within relatively developmentally homogeneous samples is examined and illustrates the effect of reduced variance among ratees on generalizability. Forecasts for g coefficients of various D study designs demonstrate how higher generalizability could be achieved by increasing the number of raters or items. In summary, the research presented illustrates the importance of and procedures for evaluating the generalizability of a set of scores in a particular research context.

  14. 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.

  15. Evaluating digestion efficiency in full-scale anaerobic digesters by identifying active microbial populations through the lens of microbial activity

    NASA Astrophysics Data System (ADS)

    Mei, Ran; Narihiro, Takashi; Nobu, Masaru K.; Kuroda, Kyohei; Liu, Wen-Tso

    2016-09-01

    Anaerobic digestion is a common technology to biologically stabilize wasted solids produced in municipal wastewater treatment. Its efficiency is usually evaluated by calculating the reduction in volatile solids, which assumes no biomass growth associated with digestion. To determine whether this assumption is valid and further evaluate digestion efficiency, this study sampled 35 digester sludge from different reactors at multiple time points together with the feed biomass in a full-scale water reclamation plant at Chicago, Illinois. The microbial communities were characterized using Illumina sequencing technology based on 16S rRNA and 16S rRNA gene (rDNA). 74 core microbial populations were identified and represented 58.7% of the entire digester community. Among them, active populations were first identified using the ratio of 16S rRNA and 16S rDNA (rRNA/rDNA) for individual populations, but this approach failed to generate consistent results. Subsequently, a recently proposed mass balance model was applied to calculate the specific growth rate (μ), and this approach successfully identified active microbial populations in digester (positive μ) that could play important roles than those with negative μ. It was further estimated that 82% of microbial populations in the feed sludge were digested in comparison with less than 50% calculated using current equations.

  16. Evaluating digestion efficiency in full-scale anaerobic digesters by identifying active microbial populations through the lens of microbial activity

    PubMed Central

    Mei, Ran; Narihiro, Takashi; Nobu, Masaru K.; Kuroda, Kyohei; Liu, Wen-Tso

    2016-01-01

    Anaerobic digestion is a common technology to biologically stabilize wasted solids produced in municipal wastewater treatment. Its efficiency is usually evaluated by calculating the reduction in volatile solids, which assumes no biomass growth associated with digestion. To determine whether this assumption is valid and further evaluate digestion efficiency, this study sampled 35 digester sludge from different reactors at multiple time points together with the feed biomass in a full-scale water reclamation plant at Chicago, Illinois. The microbial communities were characterized using Illumina sequencing technology based on 16S rRNA and 16S rRNA gene (rDNA). 74 core microbial populations were identified and represented 58.7% of the entire digester community. Among them, active populations were first identified using the ratio of 16S rRNA and 16S rDNA (rRNA/rDNA) for individual populations, but this approach failed to generate consistent results. Subsequently, a recently proposed mass balance model was applied to calculate the specific growth rate (μ), and this approach successfully identified active microbial populations in digester (positive μ) that could play important roles than those with negative μ. It was further estimated that 82% of microbial populations in the feed sludge were digested in comparison with less than 50% calculated using current equations. PMID:27666090

  17. 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

  18. Restricted growth of U-type infectious haematopoietic necrosis virus (IHNV) in rainbow trout cells may be linked to casein kinase II activity.

    PubMed

    Park, J W; Moon, C H; Harmache, A; Wargo, A R; Purcell, M K; Bremont, M; Kurath, G

    2011-02-01

    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

  19. Virulent Mycobacterium fortuitum Restricts NO Production by a Gamma Interferon-Activated J774 Cell Line and Phagosome-Lysosome Fusion

    PubMed Central

    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

    2002-01-01

    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 (Mφ) 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-γ) were infected with SmOp or SmTr M. fortuitum. We showed that SmOp and SmTr induced different levels of nitric oxide (NO) production by IFN-γ-stimulated Mφ. Indeed, the amount of IFN-γ-induced NO production by J774 cells was 4.8 to 9.0 times higher by SmOp (23.1 to 37.7 μM) compared to SmTr infection (3.9 to 4.8 μM) (P = 0.0332), indicating that virulent SmTr bacilli restricted NO production. In addition, IFN-γ-induced NO production by Mφ 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-γ-induced NO production, resisting nitrogen toxic radicals, and limiting phagosome fusion with lysosomes. PMID:12228291

  20. Large-scale isolation and cytotoxicity of extracellular vesicles derived from activated human natural killer cells

    PubMed Central

    Jong, Ambrose Y.; Wu, Chun-Hua; Li, Jingbo; Sun, Jianping; Fabbri, Muller; Wayne, Alan S.; Seeger, Robert C.

    2017-01-01

    ABSTRACT Extracellular vesicles (EVs) have been the focus of great interest, as they appear to be involved in numerous important cellular processes. They deliver bioactive macromolecules such as proteins, lipids, and nucleic acids, allowing intercellular communication in multicellular organisms. EVs are secreted by all cell types, including immune cells such as natural killer cells (NK), and they may play important roles in the immune system. Currently, a large-scale procedure to obtain functional NK EVs is lacking, limiting their use clinically. In this report, we present a simple, robust, and cost-effective method to isolate a large quantity of NK EVs. After propagating and activating NK cells ex vivo and then incubating them in exosome-free medium for 48 h, EVs were isolated using a polymer precipitation method. The isolated vesicles contain the tetraspanin CD63, an EV marker, and associated proteins (fibronectin), but are devoid of cytochrome C, a cytoplasmic marker. Nanoparticle tracking analysis showed a size distribution between 100 and 200 nm while transmission electron microscopy imaging displayed vesicles with an oval shape and comparable sizes, fulfilling the definition of EV. Importantly, isolated EV fractions were cytotoxic against cancer cells. Furthermore, our results demonstrate for the first time that isolated activated NK (aNK) cell EVs contain the cytotoxic proteins perforin, granulysin, and granzymes A and B, incorporated from the aNK cells. Activation of caspase -3, -7 and -9 was detected in cancer cells incubated with aNK EVs, and caspase inhibitors blocked aNK EV-induced cytotoxicity, suggesting that aNK EVs activate caspase pathways in target cells. The ability to isolate functional aNK EVs on a large scale may lead to new clinical applications. Abbreviations: NK: natural killer cells; activated NK (aNK) cells; EVs: extracellular vesicles; ALL: acute lymphoblastic leukaemia; aAPC: artificial antigen-presenting cell; TEM: transmission

  1. Meso Scale Impacy On Biological Activity In The NE Atlantic : Pomme

    NASA Astrophysics Data System (ADS)

    Memery, L.; Pomme Team

    The Programme Océan Multidisciplinaire Méso Echelle (POMME) seeks to under- stand the impact of meso scale dynamics on mode water formation and subduction, and on the seasonal evolution of water mass characteristics in the NE Atlantic ocean (15-210W, 38-45N). The field work, achieved in 2001,was based on three 6 week cruises with two vessels, nine moorings equipped with current-meters and other in- struments, including four with sediment traps, and over100 drifters and buoys. Real time data assimilation was used to optimise the meso scale surveys by the two ves- sels. The observation array will be described, and first results will be presented. A significant meso scale signal was observed in this low-energy region, including a few coherent structures. Their biological impact of the structures is strong mostly at the fronts located near the rims of the eddies. On the other hand, we did not observe sys- tematic differences between cyclones and anticyclones. The biological production had already started in the south in February, and has presented a steady, although strong, increase until mid May in the north. In September, the region is strongly oligotrophic and usually heterotrophic with high level of bacterial activity, and strong modifica- tions of phytoplankton and zooplankton populations. The heterogeneity driven by the fronts between eddies is large during all the seasons. This area of the North Atlantic is a CO2 sink in winter and spring and a CO2 source in late summer and early fall.

  2. Validation of the Social Networking Activity Intensity Scale among Junior Middle School Students in China

    PubMed Central

    Li, Jibin; Lau, Joseph T. F.; Mo, Phoenix K. H.; Su, Xuefen; Wu, Anise M. S.; Tang, Jie; Qin, Zuguo

    2016-01-01

    Background Online social networking use has been integrated into adolescents’ daily life and the intensity of online social networking use may have important consequences on adolescents’ well-being. However, there are few validated instruments to measure social networking use intensity. The present study aims to develop the Social Networking Activity Intensity Scale (SNAIS) and validate it among junior middle school students in China. Methods A total of 910 students who were social networking users were recruited from two junior middle schools in Guangzhou, and 114 students were retested after two weeks to examine the test-retest reliability. The psychometrics of the SNAIS were estimated using appropriate statistical methods. Results Two factors, Social Function Use Intensity (SFUI) and Entertainment Function Use Intensity (EFUI), were clearly identified by both exploratory and confirmatory factor analyses. No ceiling or floor effects were observed for the SNAIS and its two subscales. The SNAIS and its two subscales exhibited acceptable reliability (Cronbach’s alpha = 0.89, 0.90 and 0.60, and test-retest Intra-class Correlation Coefficient = 0.85, 0.87 and 0.67 for Overall scale, SFUI and EFUI subscale, respectively, p<0.001). As expected, the SNAIS and its subscale scores were correlated significantly with emotional connection to social networking, social networking addiction, Internet addiction, and characteristics related to social networking use. Conclusions The SNAIS is an easily self-administered scale with good psychometric properties. It would facilitate more research in this field worldwide and specifically in the Chinese population. PMID:27798699

  3. Recovery of cellulase activity after ethanol stripping in a novel pilot-scale unit.

    PubMed

    Skovgaard, Pernille Anastasia; Christensen, Børge Holm; Felby, Claus; Jørgensen, Henning

    2014-04-01

    Recycling of enzymes has a potential interest during cellulosic bioethanol production as purchasing enzymes is one of the largest expenses in the process. By recycling enzymes after distillation, loss of sugars and ethanol are avoided, but depending on the distillation temperature, there is a potential risk of enzyme degradation. Studies of the rate of enzyme denaturation based on estimation of the denaturation constant K D was performed using a novel distillation setup allowing stripping of ethanol at 50-65 °C. Experiments were performed in a pilot-scale stripper, where the effect of temperature (55-65 °C) and exposure to gas-liquid and liquid-heat transmission interfaces were tested on a mesophilic and thermostable enzyme mixture in fiber beer and buffer. Lab-scale tests were included in addition to the pilot-scale experiments to study the effect of shear, ethanol concentration, and PEG on enzyme stability. When increasing the temperature (up to 65 °C) or ethanol content (up to 7.5 % w/v), the denaturation rate of the enzymes increased. Enzyme denaturation occurred slower when the experiments were performed in fiber beer compared to buffer only, which could be due to PEG or other stabilizing substances in fiber beer. However, at extreme conditions with high temperature (65 °C) and ethanol content (7.5 % w/v), PEG had no enzyme stabilizing effect. The novel distillation setup proved to be useful for maintaining enzyme activity during ethanol extraction.

  4. A broad-scale comparison of aerobic activity levels in vertebrates: endotherms versus ectotherms.

    PubMed

    Gillooly, James F; Gomez, Juan Pablo; Mavrodiev, Evgeny V

    2017-02-22

    Differences in the limits and range of aerobic activity levels between endotherms and ectotherms remain poorly understood, though such differences help explain basic differences in species' lifestyles (e.g. movement patterns, feeding modes, and interaction rates). We compare the limits and range of aerobic activity in endotherms (birds and mammals) and ectotherms (fishes, reptiles, and amphibians) by evaluating the body mass-dependence of VO2 max, aerobic scope, and heart mass in a phylogenetic context based on a newly constructed vertebrate supertree. Contrary to previous work, results show no significant differences in the body mass scaling of minimum and maximum oxygen consumption rates with body mass within endotherms or ectotherms. For a given body mass, resting rates and maximum rates were 24-fold and 30-fold lower, respectively, in ectotherms than endotherms. Factorial aerobic scope ranged from five to eight in both groups, with scope in endotherms showing a modest body mass-dependence. Finally, maximum consumption rates and aerobic scope were positively correlated with residual heart mass. Together, these results quantify similarities and differences in the potential for aerobic activity among ectotherms and endotherms from diverse environments. They provide insights into the models and mechanisms that may underlie the body mass-dependence of oxygen consumption.

  5. 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.

  6. Frequencies of restriction sites.

    PubMed Central

    Waterman, M S

    1983-01-01

    Restriction sites or other sequence patterns are usually assumed to occur according to a Poisson distribution with mean equal to the reciprocal of the probability of the given site or pattern. For situations where non-overlapping occurrences of patterns, such as restriction sites, are the objects of interest, this note shows that the Poisson assumption is frequently misleading. Both the case of base composition (independent bases) and of dinucleotide frequencies (Markov chains) are treated. Moreover, a new technique is presented which allows treatment of collections of patterns, where the departure from the Poisson assumption is even more striking. This later case includes double digests, and an example of a five enzyme digest is included. PMID:6324109

  7. 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

  8. 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.

  9. Pilot-scale study of powdered activated carbon recirculation for micropollutant removal.

    PubMed

    Meinel, F; Sperlich, A; Jekel, M

    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.

  10. δ-SUNSPOT FORMATION IN SIMULATION OF ACTIVE-REGION-SCALE FLUX EMERGENCE

    SciTech Connect

    Fang, Fang; Fan, Yuhong

    2015-06-10

    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. Reliability of the Chinese Version of the Activities-specific Balance Confidence Scale

    PubMed Central

    Hsu, Priscilla C.; Miller, William C.

    2012-01-01

    Purpose To translate the Activities-specific Balance Confidence (ABC) Scale into a Chinese version and assess the reliability between Chinese versions and between Chinese and English versions of this outcome measure. Method Descriptive study using a 4-week test-retest design. Data were collected from a convenience sample of community living Chinese immigrants. Of the 79 participants, data from 71 subjects were included in the analysis. Two subsamples were formed to assess the reliability between Chinese versions (n=33) and between Chinese and English versions (n=38) of the scale. Results Internal consistency of the ABC was 0.98. Test-retest reliability was ICC=0.87 (95% CI, 0.76–0.93) for the Chinese versions and ICC = 0.88 (95% CI, 0.78–0.94) for Chinese and English versions. The total group ICC=.90 (95% CI, 0.84–0.94). Conclusions Balance confidence has been identified as an important area for clinical and research inquiry however collecting this information from Chinese speaking individuals has been limited by a lack of language specific measures. The Chinese version of the ABC has demonstrated acceptable measurement properties in this sample and should permit measurement of this unique construct in the Chinese population. PMID:17083176

  12. 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.

  13. 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.

  14. Activated scaling in disorder-rounded first-order quantum phase transitions

    NASA Astrophysics Data System (ADS)

    Bellafard, Arash; Chakravarty, Sudip

    2016-09-01

    First-order phase transitions, classical or quantum, subject to randomness coupled to energylike variables (bond randomness) can be rounded, resulting in continuous transitions (emergent criticality). We study perhaps the simplest such model, the quantum three-color Ashkin-Teller model, and show that the quantum critical point in (1 +1 ) dimension is an unusual one, with activated scaling at the critical point and Griffiths-McCoy phase away from it. The behavior is similar to the transverse random field Ising model, even though the pure system has a first-order transition in this case. We believe that this fact must be attended to when discussing quantum critical points in numerous physical systems.

  15. 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.

  16. Stress-related noradrenergic activity prompts large-scale neural network reconfiguration.

    PubMed

    Hermans, Erno J; van Marle, Hein J F; Ossewaarde, Lindsey; Henckens, Marloes J A G; Qin, Shaozheng; van Kesteren, Marlieke T R; Schoots, Vincent C; Cousijn, Helena; Rijpkema, Mark; Oostenveld, Robert; Fernández, Guillén

    2011-11-25

    Acute stress shifts the brain into a state that fosters rapid defense mechanisms. Stress-related neuromodulators are thought to trigger this change by altering properties of large-scale neural populations throughout the brain. We investigated this brain-state shift in humans. During exposure to a fear-related acute stressor, responsiveness and interconnectivity within a network including cortical (frontoinsular, dorsal anterior cingulate, inferotemporal, and temporoparietal) and subcortical (amygdala, thalamus, hypothalamus, and midbrain) regions increased as a function of stress response magnitudes. β-adrenergic receptor blockade, but not cortisol synthesis inhibition, diminished this increase. Thus, our findings reveal that noradrenergic activation during acute stress results in prolonged coupling within a distributed network that integrates information exchange between regions involved in autonomic-neuroendocrine control and vigilant attentional reorienting.

  17. An examination of adolescent bone tumor patient responses on the Activities Scale for Kids (ASK).

    PubMed

    Piscione, P Janine; Davis, Aileen M; Young, Nancy L

    2014-05-01

    This study provides an examination of responses on the Activities Scale for Kids, performance version (ASKp), for evaluating physical function in adolescents with malignant lower extremity bone tumors. Twenty-one participants (ages 10.4 to 17.9 years), who had tumor resection surgery, completed the ASKp on two occasions. ASKp data were examined for ceiling and/or floor effects, item distributions, and Not Applicable (NA) responses, as well as textual comments. Ceiling effects were 12.5% and 19%, and 0% demonstrated floor effects. The extreme response options were chosen most frequently, and approximately one third of respondents used NA more than 10% of the time. Overall, this population demonstrated moderately high NA rates and higher than anticipated ceiling effects on the ASKp. These data suggest that caution should be taken when interpreting item-level data in this population and further studies guiding the scoring and interpretation of NA responses are recommended.

  18. A coupled, pore-scale model for methanogenic microbial activity in underground hydrogen storage

    NASA Astrophysics Data System (ADS)

    Ebigbo, Anozie; Golfier, Fabrice; Quintard, Michel

    2013-11-01

    Underground hydrogen storage (UHS) as a means of energy storage is an efficient way of compensating for seasonal fluctuations in the availability of energy. One important factor which influences this technology is the activity of methanogenic microorganisms capable of utilising hydrogen and carbon dioxide for metabolism and leading to a change in the stored gas composition. A coupled, pore-scale model is presented which aids in the investigation of the mechanisms that govern the conversion of hydrogen to methane, i.e. advective hydrogen flow, its diffusion into microbial biofilms of multiple species, and its consumption within these biofilms. The model assumes that spherical grains are coated by a film of residual water and treats the biofilm development within each film in a quasi one-dimensional manner. A sample simulation using the presented model illustrates the biofilm growth process in these films as well as the competition between three different microbial species: methanogens, acetogens, and acetotrophs.

  19. 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.

  20. Utilizing Nst Data To Look For Connection Between Photospheric Dynamics And Small-scale Chromospheric Activity

    NASA Astrophysics Data System (ADS)

    Yurchyshyn, Vasyl B.

    2011-05-01

    The largest ground-based solar telescope, the new solar telescope (NST) of Big Bear Solar Observatory now allows us to address many important issues of coupling between the photosphere and chromosphere by means of simultaneous observations of photospheric granulation with well resolved bright points (BPs) and associated dynamics in the low chromosphere, as seen in H-alpha spectral line. Excellent seeing conditions, augmented with an adaptive optics system and speckle-reconstruction applications produce diffraction limited images. We use these data to search for any possible connection between typical dynamics of bright points (collision, clustering and rapid motions) and chromospheric activity, such as jets that are visible on all scales down to the smallest resolved features. In this presentation we will highlight the most important findings, which include the following. 1) In mostly unipolar coronal holes, the majority of colliding/interacting BPs are not associated with any detectable chromospheric activity. This means that the component reconnection, presumably occurring when the same polarity BPs interact, may not be very effective in producing chromospheric flows. We speculate that interaction of opposite polarity BPs may be more effective in generating up-flows. 2) NST/TiO images further reveal the hidden structure of plasma vortex tubes, previously predicted by Steiner et al. Besides the bright granular lane, a vortex tube structure also includes rapidly developing bright grain co-spatial with the tube's axis. Finally, some vortex tube events, detected in a CH data set, are co-spatial with small-scale chromospheric jets, which suggests that they may be associated with new magnetic flux emerging within a granule.

  1. 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…

  2. 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

  3. 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.

  4. 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…

  5. Promoting Leisure Physical Activity Participation among Adults with Intellectual Disabilities: Validation of Self-Efficacy and Social Support Scales

    ERIC Educational Resources Information Center

    Peterson, Jana J.; Peterson, N. Andrew; Lowe, John B.; Nothwehr, Faryle K.

    2009-01-01

    Background: Many individuals with intellectual disabilities are not sufficiently active for availing health benefits. Little is known about correlates of physical activity among this population on which to build health promotion interventions. Materials and Methods: We developed scales for measurement of self-efficacy and social support for…

  6. Large-Scale Investigation of the Role of Trait Activation Theory for Understanding Assessment Center Convergent and Discriminant Validity

    ERIC Educational Resources Information Center

    Lievens, Filip; Chasteen, Christopher S.; Day, Eric Anthony; Christiansen, Neil D.

    2006-01-01

    This study used trait activation theory as a theoretical framework to conduct a large-scale test of the interactionist explanation of the convergent and discriminant validity findings obtained in assessment centers. Trait activation theory specifies the conditions in which cross-situationally consistent and inconsistent candidate performances are…

  7. Identification of two immunogenic domains of the prion protein--PrP--which activate class II-restricted T cells and elicit antibody responses against the native molecule.

    PubMed

    Gregoire, Sylvie; Logre, Caroline; Metharom, Pat; Loing, Estelle; Chomilier, Jacques; Rosset, Martine Bruley; Aucouturier, Pierre; Carnaud, Claude

    2004-07-01

    Recent reports suggest that immunity against the prion protein (PrP) retards transmissible spongiform encephalopathies progression in infected mice. A major obstacle to the development of vaccines comes from the fact that PrP is poorly immunogenic, as it is seen as self by the host immune system. Additional questions concern the immune mechanisms involved in protection and the risk of eliciting adverse reactions in the central nervous system of treated patients. Peptide-based vaccines offer an attractive strategy to overcome these difficulties. We have undertaken the identification of the immunogenic regions of PrP, which trigger helper T cells (Th) associated with antibody production. Our results identify two main regions, one between the structured and flexible portion of PrP (98-127) and a second between alpha 1 and alpha 2 helix (143-187). Peptides (30-mer) corresponding to these regions elicit class II-restricted Th cells and antibody production against native PrP and could therefore be of potential interest for a peptide-based vaccination.

  8. The association between the social and communication elements of autism, and repetitive/restrictive behaviours and activities: a review of the literature.

    PubMed

    Kuenssberg, Renate; McKenzie, Karen; Jones, Jill

    2011-01-01

    Research continues to try and pinpoint the etiological role of particular genes and brain structure in autistic spectrum disorder (ASD), but despite a host of biological, genetic and neuropsychological research, the symptom profile of pervasive developmental disorders (PDDs) are not yet linked to etiological theory. Debate continues around whether or not there is one single dimension that incorporates the three criteria domains of social difficulties, communication deficits and repetitive or restrictive interests and behaviours as a unitary 'ASD' concept, or whether PDD as they are currently described represent the co-occurrence of separate sub-domains of developmental difficulties. Although the three criteria need to be met for a diagnosis of PDD to be made, the association between them remains unclear. This review highlights that the majority of the literature that looks at the triad of impairments suggests the symptom structure does not match that proposed by diagnostic manuals, and that the triad may no longer fit as the best way to conceptualize ASD.

  9. Restriction of Range Effects on the New MCAT's Predictive Validity.

    ERIC Educational Resources Information Center

    Hynes, Kevin; Givner, Nathaniel

    1981-01-01

    Changes were studied that occur when the correlations between the six Medical College Admission Test scales and the scores on the Part I examination of the National Board of Medical Examiners are corrected for restriction of range. (MLW)

  10. 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.

  11. 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.

  12. Pilot scale study on retrofitting conventional activated sludge plant for biological nutrient removal.

    PubMed

    Chiang, W W; Qasim, S R; Zhu, G; Crosby, E C

    1999-01-01

    Eutrophication of receiving waters due to the discharge of nitrogen and phosphorus through the wastewater effluent has received much interest in recent years. Numerous techniques have been proposed and aimed at retrofitting the existing conventional activated sludge process for nutrient removal. A pilot-scale research program was conducted to evaluate the effectiveness of a biological nutrient process for this purpose. The results indicated that creating an anoxic/anaerobic zone before aeration basin significantly enhances total phosphorus (TP) and total nitrogen (TN) removal. Without internal cycle, about 80 percent TP and TN removal were respectively achieved under their optimal conditions. However, adverse trends for phosphorus and nitrogen removal were observed when the ratio of return sludge to the influent was varied in the range between 0.5 and 3.0. The total phosphorus removal decreased as the concentration of BOD5 in the mixture of influent and return sludge decreased. Improved sludge settling properties and reduced foaming problems were also observed during the pilot plant operation. Based upon experimental results, the strategies to modify an existing conventional activated sludge plant into a biological nutrient removal (BNR) system are discussed.

  13. 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.

  14. The influence of lightning activity and anthropogenic factors on large-scale characteristics of natural fires

    NASA Astrophysics Data System (ADS)

    Eliseev, A. V.; Mokhov, I. I.; Chernokulsky, A. V.

    2017-01-01

    A module for simulating of natural fires (NFs) in the climate model of the A.M. Obukhov Institute of Atmospheric Physics, Russian Academy of Sciences (IAP RAS CM), is extended with respect to the influence of lightning activity and population density on the ignition frequency and fire suppression. The IAP RAS CM is used to perform numerical experiments in accordance with the conditions of the project that intercompares climate models, CMIP5 (Coupled Models Intercomparison Project, phase 5). The frequency of lightning flashes was assigned in accordance with the LIS/OTD satellite data. In the calculations performed, anthropogenic ignitions play an important role in NF occurrences, except for regions at subpolar latitudes and, to a lesser degree, tropical and subtropical regions. Taking into account the dependence of fire frequency on lightning activity and population density intensifies the influence of characteristics of natural fires on the climate changes in tropics and subtropics as compared to the version of the IAP RAS CM that does not take the influence of ignition sources on the large-scale characteristics of NFs into consideration.

  15. 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

  16. 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

  17. Arctigenin functions as a selective agonist of estrogen receptor β to restrict mTORC1 activation and consequent Th17 differentiation.

    PubMed

    Wu, Xin; Tong, Bei; Yang, Yan; Luo, Jinque; Yuan, Xusheng; Wei, Zhifeng; Yue, Mengfan; Xia, Yufeng; Dai, Yue

    2016-12-20

    Arctigenin was previously proven to inhibit Th17 cell differentiation and thereby attenuate colitis in mice by down-regulating the activation of mechanistic target of rapamycin complex 1 (mTORC1). The present study was performed to address its underlying mechanism in view of estrogen receptor (ER). The specific antagonist PHTPP or siRNA of ERβ largely diminished the inhibitory effect of arctigenin on the mTORC1 activation in T cell lines and primary CD4+ T cells under Th17-polarization condition, suggesting that arctigenin functioned in an ERβ-dependent manner. Moreover, arctigenin was recognized to be an agonist of ERβ, which could bind to ERβ with a moderate affinity, promote dissociation of ERβ/HSP90 complex and nuclear translocation and phosphorylation of ERβ, and increase the transcription activity. Following activation of ERβ, arctigenin inhibited the activity of mTORC1 by disruption of ERβ-raptor-mTOR complex assembly. Deficiency of ERβ markedly abolished arctigenin-mediated inhibition of Th17 cell differentiation. In colitis mice, the activation of ERβ, inhibition of mTORC1 activation and Th17 response by arctigenin were abolished by PHTPP treatment. In conclusion, ERβ might be the target protein of arctigenin responsible for inhibition of mTORC1 activation and resultant prevention of Th17 cell differentiation and colitis development.

  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.

  20. Parsec-scale Faraday rotation and polarization of 20 active galactic nuclei jets

    NASA Astrophysics Data System (ADS)

    Kravchenko, E. V.; Kovalev, Y. Y.; Sokolovsky, K. V.

    2017-01-01

    We perform polarimetry analysis of 20 active galactic nuclei (AGN) jets using the Very Long Baseline Array (VLBA) at 1.4, 1.6, 2.2, 2.4, 4.6, 5.0, 8.1, 8.4, and 15.4 GHz. The study allowed us to investigate linearly polarized properties of the jets at parsec-scales: distribution of the Faraday rotation measure (RM) and fractional polarization along the jets, Faraday effects and structure of Faraday-corrected polarization images. Wavelength-dependence of the fractional polarization and polarization angle is consistent with external Faraday rotation, while some sources show internal rotation. The RM changes along the jets, systematically increasing its value towards synchrotron self-absorbed cores at shorter wavelengths. The highest core RM reaches 16,900 rad m-2 in the source rest frame for the quasar 0952+179, suggesting the presence of highly magnetized, dense media in these regions. The typical RM of transparent jet regions has values of an order of a hundred rad m-2 . Significant transverse rotation measure gradients are observed in seven sources. The magnetic field in the Faraday screen has no preferred orientation, and is observed to be random or regular from source to source. Half of the sources show evidence for the helical magnetic fields in their rotating magnetoionic media. At the same time jets themselves contain large-scale, ordered magnetic fields and tend to align its direction with the jet flow. The observed variety of polarized signatures can be explained by a model of spine-sheath jet structure.

  1. 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.

  2. 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.

  3. Haemolytic activity of the Streptococcus milleri group' and relationship between haemolysis restricted to human red blood cells and pathogenicity in S. intermedius.

    PubMed

    Jacobs, J A; Schot, C S; Schouls, L M

    2000-01-01

    A collection of 297 clinically documented 'Streptococcus milleri' strains, identified to the genotype level by 16S rRNA gene hydridisation, was screened for haemolysis of human and animal red blood cells. Forty-nine strains (65%) of the S. intermedius genotype displayed haemolysis restricted to human blood; they were named 'exclusive human haemolytic' (EHH) S. intermedius strains. The 26 remaining S. intermedius strains were named S. intermedius non-EHH strains. Quantitative studies on the haemolysis indicated that intermedilysin was the factor involved. The S. intermedius EHH strains represented the S. intermedius phenotype, whereas the S. intermedius non-EHH strains were phenotypically characteristic of S. constellatus. The complete 16S rRNA sequences of the S. intermedius EHH strains exhibited identity with S. intermedius strains ATCC 27335 (= NCDO 2227, NCTC 11324); the 16S rRNA sequences of the S. intermedius non-EHH strains were identical to S. constellatus strain ATCC 27823 (= NCDO 2226, NCTC 11325) except for positions 228 and 229 that carried an S. intermedius sequence signature. The 16S sequence similarities between the non-EHH strains and the S. constellatus and the S. intermedius type strains were 99.5% and 98.6%, respectively. Hybridisations of the complete 16S rRNA genes with oligonucleotide probes indicated a 16S rRNA homogeneity within the S. intermedius EHH and the non-EHH strains respectively. The S. intermedius EHH strains were isolated most frequently from infection- and abscess-related specimens. The present data emphasise the genetic variability within the S. constellatus species and redefine the S. intermedius species as a homogeneous group at the 16S rRNA level.

  4. A179L, a viral Bcl-2 homologue, targets the core Bcl-2 apoptotic machinery and its upstream BH3 activators with selective binding restrictions for Bid and Noxa

    PubMed Central

    Galindo, Inmaculada; Hernaez, Bruno; Díaz-Gil, Gema; Escribano, Jose M.; Alonso, Covadonga

    2008-01-01

    Several large DNA viruses encode Bcl-2 protein homologues involved in the regulation of the cellular apoptosis cascade. This regulation often involves the interaction of these viral proteins with diverse cellular Bcl-2 family members. We have identified the specific interactions of A179L, an African swine fever virus (ASFV) Bcl-2 homologue, with the active forms of the porcine BH3-only Bid protein (truncated Bid p13 and p15). Transient expression of ASFV A179L gene in Vero cells prevented apoptosis induced by these active forms of Bid protein. Interestingly, A179L protein was able to interact, also with the main core Bcl-2 proapoptotic proteins Bax and Bak, and with several BH3-only proteins with selective binding restrictions for full length Bid and Noxa. These results suggest a fine regulation for A179L action in the suppression of apoptosis in infected cells which is essential for efficient virus replication. PMID:18329683

  5. Large-Scale Activity in the Bastille Day 2000 Solar Event

    NASA Astrophysics Data System (ADS)

    Chertok, I. M.; Grechnev, V. V.

    2005-06-01

    We have analyzed dimmings, i.e., regions of temporarily reduced brightness, and manifestations of a coronal wave in the famous event of 14 July 2000 using images produced with the EUV telescope SOHO/EIT. Our analysis was inspired by a paper by Andrews (2001, Solar Phys. 204, 181 (Paper I)), in which this event was studied using running-difference EIT images at 195 Å formed by subtraction of a previous image from each current one. Such images emphasize changes of the brightness, location, and configuration of observed structures occurring during the 12-min interval between two subsequent heliograms. However, they distort the picture of large-scale disturbances caused by a CME, particularly, dimmings. A real picture of dimmings can be obtained from fixed-base difference ‘de-rotated’ images. The latter are formed in two stages: first, the solar rotation is compensated using three-dimensional rotation of all images (‘de-rotation’) to the time of a pre-event heliogram, here 10:00 UT, and then the base heliogram is subtracted from all others. We show real dimmings to be essentially different from those described by Andrews (Paper I). The restructuring of large-scale magnetic fields in the corona in connection with the CME was accompanied by the appearance and growth of two large dimmings. One of them was located along the central meridian, southward of the eruption center, at the place of the pre-eruption arcade. Another dimming occupied the space between the flare region and a remote western active region. Several smaller dimmings were observed virtually over the whole solar disk, especially, within the northwest quadrant. We have also revealed a propagating disturbance with properties of a coronal wave in the northern polar sector, where no dimmings were observed. This fact is discussed in the context of probable association between dimmings and coronal waves. Having suppressed the ‘snowstorm’ produced in the EIT images by energetic particles, we have

  6. Activity-dependent synaptic GRIP1 accumulation drives synaptic scaling up in response to action potential blockade.

    PubMed

    Gainey, Melanie A; Tatavarty, Vedakumar; Nahmani, Marc; Lin, Heather; Turrigiano, Gina G

    2015-07-07

    Synaptic scaling is a form of homeostatic plasticity that stabilizes neuronal firing in response to changes in synapse number and strength. Scaling up in response to action-potential blockade is accomplished through increased synaptic accumulation of GluA2-containing AMPA receptors (AMPAR), but the receptor trafficking steps that drive this process remain largely obscure. Here, we show that the AMPAR-binding protein glutamate receptor-interacting protein-1 (GRIP1) is essential for regulated synaptic AMPAR accumulation during scaling up. Synaptic abundance of GRIP1 was enhanced by activity deprivation, directly increasing synaptic GRIP1 abundance through overexpression increased the amplitude of AMPA miniature excitatory postsynaptic currents (mEPSCs), and shRNA-mediated GRIP1 knockdown prevented scaling up of AMPA mEPSCs. Furthermore, knockdown and replace experiments targeting either GRIP1 or GluA2 revealed that scaling up requires the interaction between GRIP1 and GluA2. Finally, GRIP1 synaptic accumulation during scaling up did not require GluA2 binding. Taken together, our data support a model in which activity-dependent trafficking of GRIP1 to synaptic sites drives the forward trafficking and enhanced synaptic accumulation of GluA2-containing AMPAR during synaptic scaling up.

  7. School restrictions on outdoor activities and weight status in adolescent children after Japan’s 2011 Fukushima Nuclear Power Plant disaster: a mid-term to long-term retrospective analysis

    PubMed Central

    Nomura, Shuhei; Blangiardo, Marta; Hodgson, Susan

    2016-01-01

    Objective Radiation fears following Japan's 2011 Fukushima nuclear disaster affected levels of physical activity in local children. We assessed the postdisaster versus predisaster weight status in school children and evaluated to what extent school restrictions on outdoor activities that were intended to reduce radiation exposure risk affected child weight. Participants We considered children aged 13–15 years from 4 of the 5 secondary schools in Soma City (n=1030, 99.1% of all children in the city), located in 35–50 km from the Fukushima nuclear plant, postdisaster (2012 and 2015) and predisaster (2010). Methods Weight status, in terms of body mass index (BMI), percentage of overweight (POW) and incidence of obesity and underweight (defined as a POW ≥20% and ≤−20%, respectively) were examined and compared predisaster and postdisaster using regression models. We also constructed models to assess the impact of school restrictions on outdoor activity on weight status. Results After adjustment for covariates, a slight decrease in mean BMI and POW was detected in females in 2012 (−0.37, 95% CI −0.68 to −0.06; and −1.97, 95% CI −3.57 to −0.36, respectively). For male children, obesity incidence increased in 2012 (OR for obesity: 1.45, 95% CI 1.02 to 2.08). Compared with predisaster weight status, no significant weight change was identified in 2015 in either males or females. School restrictions on outdoor activities were not significantly associated with weight status. Conclusions 4 years following the disaster, weight status has recovered to the predisaster levels for males and females; however, a slight decrease in weight in females and a slight increase in risk of obesity were observed in males 1 year following the disaster. Our findings could be used to guide actions taken during the early phase of a radiological disaster to manage the postdisaster health risks in adolescent children. PMID:27683520

  8. Sensitivity of predicted scaling and permeability in Enhanced Geothermal Systems to Thermodynamic Data and Activity Models

    NASA Astrophysics Data System (ADS)

    Hingerl, Ferdinand F.; Wagner, Thomas; Kulik, Dmitrii A.; Kosakowski, Georg; Driesner, Thomas; Thomsen, Kaj

    2010-05-01

    A consortium of research groups from ETH Zurich, EPF Lausanne, the Paul Scherrer Institut and the University of Bonn collaborates in a comprehensive program of basic research on key aspects of the Enhanced Geothermal Systems (EGSs). As part of this GEOTHERM project (www.geotherm.ethz.ch), we concentrate on the fundamental investigation of thermodynamic models suitable for describing fluid-rock interactions at geothermal conditions. Predictions of the fluid-rock interaction in EGS still face several major challenges. Slight variations in the input thermodynamic and kinetic parameters may result in significant differences in the predicted mineral solubilities and stable assemblage. Realistic modeling of mineral precipitation in turn has implications onto our understanding of the permeability evolution of the geothermal reservoir, as well as the scaling in technical installations. In order to reasonably model an EGS, thermodynamic databases and activity models must be tailored to geothermal conditions. We therefore implemented in GEMS code the Pitzer formalism, which is the standard model used for computing thermodynamic excess properties of brines at elevated temperatures and pressures. This model, however, depends on a vast amount of interaction parameters, which are to a substantial extend unknown. Furthermore, a high order polynomial temperature interpolation makes extrapolation unreliable if not impossible. As an alternative we additionally implemented the EUNIQUAC activity model. EUNIQUAC requires fewer empirical fit parameters (only binary interaction parameters needed) and uses simpler and more stable temperature and pressure extrapolations. This results in an increase in computation speed, which is of crucial importance when performing coupled long term simulations of geothermal reservoirs. To achieve better performance under geothermal conditions, we are currently partly reformulating EUNIQUAC and refitting the existing parameter set. First results of the

  9. Counteraction of the multifunctional restriction factor tetherin

    PubMed Central

    Sauter, Daniel

    2014-01-01

    The interferon-inducible restriction factor tetherin (also known as CD317, BST-2 or HM1.24) has emerged as a key component of the antiviral immune response. Initially, tetherin was shown to restrict replication of various enveloped viruses by inhibiting the release of budding virions from infected cells. More recently, it has become clear that tetherin also acts as a pattern recognition receptor inducing NF-κB-dependent proinflammatory gene expression in virus infected cells. Whereas the ability to restrict virion release is highly conserved among mammalian tetherin orthologs and thus probably an ancient function of this protein, innate sensing seems to be an evolutionarily recent activity. The potent and broad antiviral activity of tetherin is reflected by the fact that many viruses evolved means to counteract this restriction factor. A continuous arms race with viruses has apparently driven the evolution of different isoforms of tetherin with different functional properties. Interestingly, tetherin has also been implicated in cellular processes that are unrelated to immunity, such as the organization of the apical actin network and membrane microdomains or stabilization of the Golgi apparatus. In this review, I summarize our current knowledge of the different functions of tetherin and describe the molecular strategies that viruses have evolved to antagonize or evade this multifunctional host restriction factor. PMID:24782851

  10. Development and Psychometric Properties of the Instrumental Activities of Daily Living: Compensation Scale

    PubMed Central

    Schmitter-Edgecombe, Maureen; Parsey, Carolyn; Lamb, Richard

    2014-01-01

    The Instrumental Activities of Daily Living – Compensation (IADL-C) scale was developed to capture early functional difficulties and to quantify compensatory strategy use that may mitigate functional decline in the aging population. The IADL-C was validated in a sample of cognitively healthy older adults (N=184) and individuals with mild cognitive impairment (MCI; N=92) and dementia (N=24). Factor analysis and Rasch item analysis led to the 27-item IADL-C informant questionnaire with four functional domain subscales (money and self-management, home daily living, travel and event memory, and social skills). The subscales demonstrated good internal consistency (Rasch reliability 0.80 to 0.93) and test-retest reliability (Spearman coefficients 0.70 to 0.91). The IADL-C total score and subscales showed convergent validity with other IADL measures, discriminant validity with psychosocial measures, and the ability to discriminate between diagnostic groups. The money and self management subscale showed notable difficulties for individuals with MCI, whereas difficulties with home daily living became more prominent for dementia participants. Compensatory strategy use increased in the MCI group and decreased in the dementia group. PMID:25344901

  11. Hurricane activity and the large-scale pattern of spread of an invasive plant species.

    PubMed

    Bhattarai, Ganesh P; Cronin, James T

    2014-01-01

    Disturbances are a primary facilitator of the growth and spread of invasive species. However, the effects of large-scale disturbances, such as hurricanes and tropical storms, on the broad geographic patterns of invasive species growth and spread have not been investigated. We used historical aerial imagery to determine the growth rate of invasive Phragmites australis patches in wetlands along the Atlantic and Gulf Coasts of the United States. These were relatively undisturbed wetlands where P. australis had room for unrestricted growth. Over the past several decades, invasive P. australis stands expanded in size by 6-35% per year. Based on tropical storm and hurricane activity over that same time period, we found that the frequency of hurricane-force winds explained 81% of the variation in P. australis growth over this broad geographic range. The expansion of P. australis stands was strongly and positively correlated with hurricane frequency. In light of the many climatic models that predict an increase in the frequency and intensity of hurricanes over the next century, these results suggest a strong link between climate change and species invasion and a challenging future ahead for the management of invasive species.

  12. Development and psychometric properties of the instrumental activities of daily living: compensation scale.

    PubMed

    Schmitter-Edgecombe, Maureen; Parsey, Carolyn; Lamb, Richard

    2014-12-01

    The Instrumental Activities of Daily Living - Compensation (IADL-C) scale was developed to capture early functional difficulties and to quantify compensatory strategy use that may mitigate functional decline in the aging population. The IADL-C was validated in a sample of cognitively healthy older adults (N=184) and individuals with mild cognitive impairment (MCI; N=92) and dementia (N=24). Factor analysis and Rasch item analysis led to the 27-item IADL-C informant questionnaire with four functional domain subscales (money and self-management, home daily living, travel and event memory, and social skills). The subscales demonstrated good internal consistency (Rasch reliability 0.80 to 0.93) and test-retest reliability (Spearman coefficients 0.70 to 0.91). The IADL-C total score and subscales showed convergent validity with other IADL measures, discriminant validity with psychosocial measures, and the ability to discriminate between diagnostic groups. The money and self management subscale showed notable difficulties for individuals with MCI, whereas difficulties with home daily living became more prominent for dementia participants. Compensatory strategy use increased in the MCI group and decreased in the dementia group.

  13. Nanometer Scale Titanium Surface Texturing Are Detected by Signaling Pathways Involving Transient FAK and Src Activations

    PubMed Central

    Zambuzzi, Willian F.; Bonfante, Estevam A.; Jimbo, Ryo; Hayashi, Mariko; Andersson, Martin; Alves, Gutemberg; Takamori, Esther R.; Beltrão, Paulo J.; Coelho, Paulo G.; Granjeiro, José M.

    2014-01-01

    Background It is known that physico/chemical alterations on biomaterial surfaces have the capability to modulate cellular behavior, affecting early tissue repair. Such surface modifications are aimed to improve early healing response and, clinically, offer the possibility to shorten the time from implant placement to functional loading. Since FAK and Src are intracellular proteins able to predict the quality of osteoblast adhesion, this study evaluated the osteoblast behavior in response to nanometer scale titanium surface texturing by monitoring FAK and Src phosphorylations. Methodology Four engineered titanium surfaces were used for the study: machined (M), dual acid-etched (DAA), resorbable media microblasted and acid-etched (MBAA), and acid-etch microblasted (AAMB). Surfaces were characterized by scanning electron microscopy, interferometry, atomic force microscopy, x-ray photoelectron spectroscopy and energy dispersive X-ray spectroscopy. Thereafter, those 4 samples were used to evaluate their cytotoxicity and interference on FAK and Src phosphorylations. Both Src and FAK were investigated by using specific antibody against specific phosphorylation sites. Principal Findings The results showed that both FAK and Src activations were differently modulated as a function of titanium surfaces physico/chemical configuration and protein adsorption. Conclusions It can be suggested that signaling pathways involving both FAK and Src could provide biomarkers to predict osteoblast adhesion onto different surfaces. PMID:24999733

  14. Active vibration control of a full scale aircraft wing using a reconfigurable controller

    NASA Astrophysics Data System (ADS)

    Prakash, Shashikala; Renjith Kumar, T. G.; Raja, S.; Dwarakanathan, D.; Subramani, H.; Karthikeyan, C.

    2016-01-01

    This work highlights the design of a Reconfigurable Active Vibration Control (AVC) System for aircraft structures using adaptive techniques. The AVC system with a multichannel capability is realized using Filtered-X Least Mean Square algorithm (FxLMS) on Xilinx Virtex-4 Field Programmable Gate Array (FPGA) platform in Very High Speed Integrated Circuits Hardware Description Language, (VHDL). The HDL design is made based on Finite State Machine (FSM) model with Floating point Intellectual Property (IP) cores for arithmetic operations. The use of FPGA facilitates to modify the system parameters even during runtime depending on the changes in user's requirements. The locations of the control actuators are optimized based on dynamic modal strain approach using genetic algorithm (GA). The developed system has been successfully deployed for the AVC testing of the full-scale wing of an all composite two seater transport aircraft. Several closed loop configurations like single channel and multi-channel control have been tested. The experimental results from the studies presented here are very encouraging. They demonstrate the usefulness of the system's reconfigurability for real time applications.

  15. Exploring Bikeability in a Suburban Metropolitan Area Using the Active Commuting Route Environment Scale (ACRES)

    PubMed Central

    Wahlgren, Lina; Schantz, Peter

    2014-01-01

    Background and Aim: Commuting by bicycle could contribute to public health, and route environments may influence this behaviour. Therefore, the aim of this study is to assess the potential associations between appraisals of the overall route environment as hindering or stimulating for bicycle commuting, with both perceptions of commuting route environmental factors in a suburban area and background factors. Methods: The Active Commuting Route Environment Scale (ACRES) was used for the assessment of bicycle commuters’ perceptions and appraisals of their route environments in the suburban parts of Greater Stockholm, Sweden. A simultaneous multiple regression analysis was used to assess the relationship between the outcome variable whether the overall route environment hinders or stimulates bicycle commuting and environmental factors (e.g., exhaust fumes, speeds of motor vehicles, greenery), as well as background factors (sex, age, education, income) as predictor variables. Results and Conclusions: The results indicate that in suburban areas, the factors aesthetics, greenery and bicycle paths seem to be, independently of each other, stimulating factors for bicycle commuting. On the other hand, flows of motor vehicles, noise, and low “directness” of the route seem to be hindering factors. A comparison of these results with those obtained from an inner urban area points to the importance of studying different types of built-up areas separately. PMID:25153462

  16. Dynamics of large-scale brain activity in normal arousal states and epileptic seizures

    NASA Astrophysics Data System (ADS)

    Robinson, P. A.; Rennie, C. J.; Rowe, D. L.

    2002-04-01

    Links between electroencephalograms (EEGs) and underlying aspects of neurophysiology and anatomy are poorly understood. Here a nonlinear continuum model of large-scale brain electrical activity is used to analyze arousal states and their stability and nonlinear dynamics for physiologically realistic parameters. A simple ordered arousal sequence in a reduced parameter space is inferred and found to be consistent with experimentally determined parameters of waking states. Instabilities arise at spectral peaks of the major clinically observed EEG rhythms-mainly slow wave, delta, theta, alpha, and sleep spindle-with each instability zone lying near its most common experimental precursor arousal states in the reduced space. Theta, alpha, and spindle instabilities evolve toward low-dimensional nonlinear limit cycles that correspond closely to EEGs of petit mal seizures for theta instability, and grand mal seizures for the other types. Nonlinear stimulus-induced entrainment and seizures are also seen, EEG spectra and potentials evoked by stimuli are reproduced, and numerous other points of experimental agreement are found. Inverse modeling enables physiological parameters underlying observed EEGs to be determined by a new, noninvasive route. This model thus provides a single, powerful framework for quantitative understanding of a wide variety of brain phenomena.

  17. The weak, fine-tuned binding of ubiquitous transcription factors to the Il-2 enhancer contributes to its T cell-restricted activity.

    PubMed Central

    Hentsch, B; Mouzaki, A; Pfeuffer, I; Rungger, D; Serfling, E

    1992-01-01

    The T lymphocyte-specific enhancers of the murine and human Interleukin 2 (Il-2) genes harbour several binding sites for ubiquitous transcription factors. All these sites for the binding of AP-1, NF-kB or Oct-1 are non-canonical sites, i.e. they differ in one or a few base pairs from consensus sequences for the optimal binding of these factors. Although the factors bind weakly to these sites, the latter are functionally important because their mutation to non-binding sites results in a decrease of inducible activity of the Il-2 enhancer. Conversion of three sites to canonical binding sites of Octamer factors, AP-1 and NF-kB results in a drastic increase in enhancer activity and the induction of the Il-2 enhancer in non-T cells, such as B cell lines, murine L cells and human HeLa cells. The introduction of two or three canonical sites into the enhancer leads to a further increase of its activity. Il-2 enhancer induction is also observed in B cells when the concentration of AP-1 and Oct factors increases as a result of cotransfections with FosB and Octamer expression plasmids. When Il-2 enhancer constructs carrying canonical factor binding sites were injected into Xenopus oocytes the strong binding of ubiquitous factors substantially overcomes the silencing effect of negatively acting factors present in resting primary T lymphocytes. These results suggest a fine-tuned interplay between ubiquitous and lymphoid-specific factors binding to and transactivating the Il-2 enhancer and show that the binding affinity of ubiquitous factors to the enhancer contributes to its cell-type specific activity. Moreover, we believe that a dramatic increase of transcriptional activity brought about by single point mutations at strategic important factor binding sites may also have relevance to the activation of nuclear oncogenes. Images PMID:1614851

  18. Early postnatal caloric restriction protects adult male intrauterine growth-restricted offspring from obesity.

    PubMed

    Garg, Meena; Thamotharan, Manikkavasagar; Dai, Yun; Thamotharan, Shanthie; Shin, Bo-Chul; Stout, David; Devaskar, Sherin U

    2012-06-01

    Postnatal ad libitum caloric intake superimposed on intrauterine growth restriction (IUGR) is associated with adult-onset obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). We hypothesized that this paradigm of prenatal nutrient deprivation-induced programming can be reversed with the introduction of early postnatal calorie restriction. Ten-month-old male rats exposed to either prenatal nutrient restriction with ad libitum postnatal intake (IUGR), pre- and postnatal nutrient restriction (IPGR), or postnatal nutrient restriction limited to the suckling phase (50% from postnatal [PN]1 to PN21) (PNGR) were compared with age-matched controls (CON). Visceral adiposity, metabolic profile, and insulin sensitivity by hyperinsulinemic-euglycemic clamps were examined. The 10-month-old male IUGR group had a 1.5- to 2.0-fold increase in subcutaneous and visceral fat (P < 0.0002) while remaining euglycemic, insulin sensitive, inactive, and exhibiting metabolic inflexibility (Vo(2)) versus CON. The IPGR group remained lean, euglycemic, insulin sensitive, and active while maintaining metabolic flexibility. The PNGR group was insulin sensitive, similar to IPGR, but less active while maintaining metabolic flexibility. We conclude that IUGR resulted in obesity without insulin resistance and energy metabolic perturbations prior to development of glucose intolerance and T2DM. Postnatal nutrient restriction superimposed on IUGR was protective, restoring metabolic normalcy to a lean and active phenotype.

  19. DNA Mutagenic Activity and Capacity for HIV-1 Restriction of the Cytidine Deaminase APOBEC3G Depends on Whether DNA or RNA Binds to Tyrosine 315.

    PubMed

    Polevoda, Bogdan; Joseph, Rebecca; Friedman, Alan E; Bennett, Ryan P; Greiner, Rebecca; De Zoysa, Thareendra; Stewart, Ryan A; Smith, Harold C

    2017-04-05

    APOBEC3G (A3G) belongs to the AID/APOBEC protein family of cytidine deaminases (CDA) that bind to nucleic acids. A3G mutates the HIV genome by deamination of dC to dU, leading to accumulation of virus-inactivating mutations. Binding to cellular RNAs inhibits A3G binding to substrate single-stranded (ss) DNA and CDA activity. RNA and ssDNA bind to the same three A3G tryptic peptides (amino acids 181-194, 314-320, and 345-374) that form parts of a continuously exposed protein surface extending from the catalytic domain in the C-terminus of A3G to its N-terminus. We show here that the A3G tyrosines 181 and 315 directly cross-link ssDNA. Binding experiments showed that a Y315A mutation alone significantly reduced A3G binding to both ssDNA and RNA, whereas Y181A and Y182A mutations only moderately affected A3G nucleic acid binding. Consistent with these findings, the Y315A mutant exhibited little to no deaminase activity in an E. coli DNA mutator reporter, while Y181A and Y182A mutants retained ~50% of wild-type A3G activity. The Y315A mutant also showed a markedly reduced ability to assemble into viral particles and had reduced antiviral activity. In uninfected cells, the impaired RNA-binding capacity of Y315A was evident by a shift of A3G from high-molecular-mass ribonucleoprotein complexes to low-molecular-mass complexes. We conclude that Y315 is essential for coordinating ssDNA interaction with or entry to the deaminase domain and hypothesize that RNA bound to Y315 may be sufficient to competitively inhibit ssDNA deaminase-dependent antiviral activity.

  20. Bikeability and methodological issues using the active commuting route environment scale (ACRES) in a metropolitan setting

    PubMed Central

    2011-01-01

    Background Route environments can positively influence people's active commuting and thereby contribute to public health. The Active Commuting Route Environment Scale (ACRES) was developed to study active commuters' perceptions of their route environments. However, bicycle commuters represent a small portion of the population in many cities and thus are difficult to study using population-based material. Therefore, the aim of this study is to expand the state of knowledge concerning the criterion-related validity of the ACRES and the representativity using an advertisement-recruited sample. Furthermore, by comparing commuting route environment profiles of inner urban and suburban areas, we provide a novel basis for understanding the relationship between environment and bikeability. Methods Bicycle commuters from Greater Stockholm, Sweden, advertisement- (n = 1379) and street-recruited (n = 93), responded to the ACRES. Traffic planning and environmental experts from the Municipality of Stockholm (n = 24) responded to a modified version of the ACRES. The criterion-related validity assessments were based on whether or not differences between the inner urban and the suburban route environments, as indicated by the experts and by four existing objective measurements, were reflected by differences in perceptions of these environments. Comparisons of ratings between advertisement- and street-recruited participants were used for the assessments of representativity. Finally, ratings of inner urban and suburban route environments were used to evaluate commuting route environment profiles. Results Differences in ratings of the inner urban and suburban route environments by the advertisement-recruited participants were in accord with the existing objective measurements and corresponded reasonably well with those of the experts. Overall, there was a reasonably good correspondence between the advertisement- and street-recruited participants' ratings. Distinct differences in

  1. Effect of restriction of working memory on reported paranormal belief.

    PubMed

    Dudley, R T

    1999-02-01

    56 college students completed Tobacyk's 1988 Revised Paranormal Belief Scale and Watson, Clark, and Tellegen's 1988 Positive and Negative Affect Scale. Experimental group participants, but not control group participants, rehearsed a five-digit number while completing the Paranormal Belief Scale. Analysis showed higher reported paranormal belief for experimental group participants but no differences on the Positive and Negative Affect Scale. Results are discussed in terms of the effect of restriction in working memory on the critical evaluation of paranormal phenomena.

  2. Identification of the impact of crime on physical activity depends upon neighbourhood scale: multilevel evidence from 203,883 Australians.

    PubMed

    Astell-Burt, Thomas; Feng, Xiaoqi; Kolt, Gregory S

    2015-01-01

    Equivocal findings on crime as a deterrent for physical activity may be due to effects of geographic scale on exposure measurement. To investigate this hypothesis, physical activity was measured in 203,883 Australians and linked to standardised crime counts within small ('Census Collection Districts'; approx. 330 residents) and larger areas ('Statistical Local Areas'; approx. 32,000 residents). A median rate ratio of 2.26 indicated substantive geographic variation in moderate-to-vigorous physical activity (MVPA). Adjusting for confounders, multilevel negative binomial regression reported lower MVPA with more crime consistently in small, but not in larger areas. Reducing small pockets of local crime may encourage more physically active lifestyles.

  3. 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

  4. 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

  5. Beaver Activity, Holocene Climate and Riparian Landscape Change Across Stream Scales in the Greater Yellowstone Ecosystem

    NASA Astrophysics Data System (ADS)

    Levine, R.; Meyer, G. A.

    2013-12-01

    Creek. On all GYE streams investigated, beaver have promoted deposition of a large volume of fine-grained organic-rich sediment, but valley-floor aggradation (vertical rise) due to beaver damming is limited to < 2.5 m, the maximum height of beaver dams, except in glacial depressions where filling occurs without damming. Initial beaver-stick deposit ages for CV streams show notable clustering ca. 5200-5000, 3800-3600, and 900-550 cal yr BP, in part consistent with other GYE sites, where ages tend to cluster in colder-wetter intervals. Beaver-stick deposits from 900-550 cal yr BP, however, overlap the drought-prone Medieval Climate Anomaly (MCA) (~1050-650 cal yr BP), a time of major fire-related debris-flow activity in Yellowstone, and minimal beaver-pond sedimentation in smaller GYE streams. The presence of beaver-stick deposits during the MCA may indicate the importance of larger streams like Odell and Red Rock Creeks in maintaining riparian zones and beaver refugia in drought-prone episodes, a critical concern with current and future warming. Overall, the long-term perspective on beaver occupancy in the GYE across a variety of stream scales provides insight into the effects of climate on ecologically critical riparian zones.

  6. Evidence and AIDS activism: HIV scale-up and the contemporary politics of knowledge in global public health.