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Sample records for calm differentially control

  1. Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial.

    Science.gov (United States)

    Colombel, Jean-Frederic; Panaccione, Remo; Bossuyt, Peter; Lukas, Milan; Baert, Filip; Vaňásek, Tomas; Danalioglu, Ahmet; Novacek, Gottfried; Armuzzi, Alessandro; Hébuterne, Xavier; Travis, Simon; Danese, Silvio; Reinisch, Walter; Sandborn, William J; Rutgeerts, Paul; Hommes, Daniel; Schreiber, Stefan; Neimark, Ezequiel; Huang, Bidan; Zhou, Qian; Mendez, Paloma; Petersson, Joel; Wallace, Kori; Robinson, Anne M; Thakkar, Roopal B; D'Haens, Geert

    2018-12-23

    Biomarkers of intestinal inflammation, such as faecal calprotectin and C-reactive protein, have been recommended for monitoring patients with Crohn's disease, but whether their use in treatment decisions improves outcomes is unknown. We aimed to compare endoscopic and clinical outcomes in patients with moderate to severe Crohn's disease who were managed with a tight control algorithm, using clinical symptoms and biomarkers, versus patients managed with a clinical management algorithm. CALM was an open-label, randomised, controlled phase 3 study, done in 22 countries at 74 hospitals and outpatient centres, which evaluated adult patients (aged 18-75 years) with active endoscopic Crohn's disease (Crohn's Disease Endoscopic Index of Severity [CDEIS] >6; sum of CDEIS subscores of >6 in one or more segments with ulcers), a Crohn's Disease Activity Index (CDAI) of 150-450 depending on dose of prednisone at baseline, and no previous use of immunomodulators or biologics. Patients were randomly assigned at a 1:1 ratio to tight control or clinical management groups, stratified by smoking status (yes or no), weight (2 years) after 8 weeks of prednisone induction therapy, or earlier if they had active disease. In both groups, treatment was escalated in a stepwise manner, from no treatment, to adalimumab induction followed by adalimumab every other week, adalimumab every week, and lastly to both weekly adalimumab and daily azathioprine. This escalation was based on meeting treatment failure criteria, which differed between groups (tight control group before and after random assignment: faecal calprotectin ≥250 μg/g, C-reactive protein ≥5mg/L, CDAI ≥150, or prednisone use in the previous week; clinical management group before random assignment: CDAI decrease of 200; clinical management group after random assignment: CDAI decrease of management group, 0·9 years [SD 1·7]; tight control group, 1·0 year [2·3]) were randomly assigned to monitoring groups (n=122 per group

  2. Increasing arousal enhances inhibitory control in calm but not excitable dogs

    Science.gov (United States)

    Bray, Emily E.; MacLean, Evan L.; Hare, Brian A.

    2015-01-01

    The emotional-reactivity hypothesis proposes that problem-solving abilities can be constrained by temperament, within and across species. One way to test this hypothesis is with the predictions of the Yerkes-Dodson law. The law posits that arousal level, a component of temperament, affects problem solving in an inverted U-shaped relationship: optimal performance is reached at intermediate levels of arousal and impeded by high and low levels. Thus, a powerful test of the emotional-reactivity hypothesis is to compare cognitive performance in dog populations that have been bred and trained based in part on their arousal levels. We therefore compared a group of pet dogs to a group of assistance dogs bred and trained for low arousal (N = 106) on a task of inhibitory control involving a detour response. Consistent with the Yerkes-Dodson law, assistance dogs, which began the test with lower levels of baseline arousal, showed improvements when arousal was artificially increased. In contrast, pet dogs, which began the test with higher levels of baseline arousal, were negatively affected when their arousal was increased. Furthermore, the dogs’ baseline levels of arousal, as measured in their rate of tail wagging, differed by population in the expected directions. Low-arousal assistance dogs showed the most inhibition in a detour task when humans eagerly encouraged them while more highly aroused pet dogs performed worst on the same task with strong encouragement. Our findings support the hypothesis that selection on temperament can have important implications for cognitive performance. PMID:26169659

  3. Increasing arousal enhances inhibitory control in calm but not excitable dogs.

    Science.gov (United States)

    Bray, Emily E; MacLean, Evan L; Hare, Brian A

    2015-11-01

    The emotional-reactivity hypothesis proposes that problem-solving abilities can be constrained by temperament, within and across species. One way to test this hypothesis is with the predictions of the Yerkes-Dodson law. The law posits that arousal level, a component of temperament, affects problem solving in an inverted U-shaped relationship: Optimal performance is reached at intermediate levels of arousal and impeded by high and low levels. Thus, a powerful test of the emotional-reactivity hypothesis is to compare cognitive performance in dog populations that have been bred and trained based in part on their arousal levels. We therefore compared a group of pet dogs to a group of assistance dogs bred and trained for low arousal (N = 106) on a task of inhibitory control involving a detour response. Consistent with the Yerkes-Dodson law, assistance dogs, which began the test with lower levels of baseline arousal, showed improvements when arousal was artificially increased. In contrast, pet dogs, which began the test with higher levels of baseline arousal, were negatively affected when their arousal was increased. Furthermore, the dogs' baseline levels of arousal, as measured in their rate of tail wagging, differed by population in the expected directions. Low-arousal assistance dogs showed the most inhibition in a detour task when humans eagerly encouraged them, while more highly aroused pet dogs performed worst on the same task with strong encouragement. Our findings support the hypothesis that selection on temperament can have important implications for cognitive performance.

  4. Calm Multi-Baryon Operators

    Directory of Open Access Journals (Sweden)

    Berkowitz Evan

    2018-01-01

    Full Text Available There are many outstanding problems in nuclear physics which require input and guidance from lattice QCD calculations of few baryons systems. However, these calculations suffer from an exponentially bad signal-to-noise problem which has prevented a controlled extrapolation to the physical point. The variational method has been applied very successfully to two-meson systems, allowing for the extraction of the two-meson states very early in Euclidean time through the use of improved single hadron operators. The sheer numerical cost of using the same techniques in two-baryon systems has so far been prohibitive. We present an alternate strategy which offers some of the same advantages as the variational method while being significantly less numerically expensive. We first use the Matrix Prony method to form an optimal linear combination of single baryon interpolating fields generated from the same source and different sink interpolating fields. Very early in Euclidean time this optimal linear combination is numerically free of excited state contamination, so we coin it a calm baryon. This calm baryon operator is then used in the construction of the two-baryon correlation functions.To test this method, we perform calculations on the WM/JLab iso-clover gauge configurations at the SU(3 flavor symmetric point with mπ~ 800 MeV — the same configurations we have previously used for the calculation of two-nucleon correlation functions. We observe the calm baryon significantly removes the excited state contamination from the two-nucleon correlation function to as early a time as the single-nucleon is improved, provided non-local (displaced nucleon sources are used. For the local two-nucleon correlation function (where both nucleons are created from the same space-time location there is still improvement, but there is significant excited state contamination in the region the single calm baryon displays no excited state contamination.

  5. The calm mouse: an animal model of stress reduction.

    Science.gov (United States)

    Gurfein, Blake T; Stamm, Andrew W; Bacchetti, Peter; Dallman, Mary F; Nadkarni, Nachiket A; Milush, Jeffrey M; Touma, Chadi; Palme, Rupert; Di Borgo, Charles Pozzo; Fromentin, Gilles; Lown-Hecht, Rachel; Konsman, Jan Pieter; Acree, Michael; Premenko-Lanier, Mary; Darcel, Nicolas; Hecht, Frederick M; Nixon, Douglas F

    2012-05-09

    Chronic stress is associated with negative health outcomes and is linked with neuroendocrine changes, deleterious effects on innate and adaptive immunity, and central nervous system neuropathology. Although stress management is commonly advocated clinically, there is insufficient mechanistic understanding of how decreasing stress affects disease pathogenesis. Therefore, we have developed a "calm mouse model" with caging enhancements designed to reduce murine stress. Male BALB/c mice were divided into four groups: control (Cntl), standard caging; calm (Calm), large caging to reduce animal density, a cardboard nest box for shelter, paper nesting material to promote innate nesting behavior, and a polycarbonate tube to mimic tunneling; control exercise (Cntl Ex), standard caging with a running wheel, known to reduce stress; and calm exercise (Calm Ex), calm caging with a running wheel. Calm, Cntl Ex and Calm Ex animals exhibited significantly less corticosterone production than Cntl animals. We also observed changes in spleen mass, and in vitro splenocyte studies demonstrated that Calm Ex animals had innate and adaptive immune responses that were more sensitive to acute handling stress than those in Cntl. Calm animals gained greater body mass than Cntl, although they had similar food intake, and we also observed changes in body composition, using magnetic resonance imaging. Together, our results suggest that the Calm mouse model represents a promising approach to studying the biological effects of stress reduction in the context of health and in conjunction with existing disease models.

  6. National guidelines for traffic calming

    CSIR Research Space (South Africa)

    Schermers, G

    1998-03-01

    Full Text Available and provides a policy framework on traffic calming. It also describes the administrative and management procedures required to meet policy objectives in the implementation and monitoring of traffic calming in urban areas. Related legal requirements, liability...

  7. Open and Calm-A randomized controlled trial evaluating a public stress reduction program in Denmark Health behavior, health promotion and society

    DEFF Research Database (Denmark)

    Jensen, Christian Gaden; Lansner, Jon; Petersen, Anders

    2015-01-01

    of a novel program: Relaxation-Response-based Mental Health Promotion (RR-MHP). Methods: The multimodal, meditation-based course was publicly entitled "Open and Calm" (OC) because it consistently trained relaxed and receptive ("Open") attention, and consciously non-intervening ("Calm") witnessing, in two...

  8. Communication and Low Mood (CALM): a randomized controlled trial of behavioural therapy for stroke patients with aphasia.

    Science.gov (United States)

    Thomas, Shirley A; Walker, Marion F; Macniven, Jamie A; Haworth, Helen; Lincoln, Nadina B

    2013-05-01

    The aim was to evaluate behavioural therapy as a treatment for low mood in people with aphasia. A randomized controlled trial comparing behavioural therapy plus usual care with a usual care control. Potential participants with aphasia after stroke were screened for the presence of low mood. Those who met the criteria and gave consent were randomly allocated. Participants were recruited from hospital wards, community rehabilitation, speech and language therapy services and stroke groups. Of 511 people with aphasia identified, 105 had low mood and were recruited. Behavioural therapy was offered for up to three months. Outcomes were assessed three and six months after random allocation. Stroke Aphasic Depression Questionnaire, Visual Analog Mood Scales 'sad' item, and Visual Analogue Self-Esteem Scale. Participants were aged 29 to 94 years (mean 67.0, SD 13.5) and 66 (63%) were men. Regression analysis showed that at three months, when baseline values and communication impairment were controlled for, group allocation was a significant predictor of the Stroke Aphasic Depression Questionnaire (P aphasia.

  9. MOBILIDADE URBANA E TRAFFIC CALMING

    Directory of Open Access Journals (Sweden)

    Priscilla Alves

    2014-09-01

    Full Text Available O objetivo do presente trabalho é o de analisar e compreender, a partir de uma discussão teórica, o conceito e aplicação das medidas moderadoras de tráfego, conhecidas como traffic calming e sua relação com a mobilidade urbana sustentável. Buscou-se conhecer a aplicação da técnica no cenário mundial assim como algumas medidas adotadas no Brasil. Os procedimentos metodológicos aqui utilizados envolvem uma pesquisa exploratória, através da literatura atual e disponível, acerca dos temas mobilidade urbana sustentável e aplicação das medidas traffic calming. Conclui-se que as medidas de moderação atuam em conformidade com os princípios da mobilidade urbana sustentável na medida em que prioriza ações para redução do tráfego motorizado, e incentiva o uso e a segurança nos deslocamentos não motorizados. Contudo, a aplicação das técnicas sem estudos prévios e um planejamento estratégico não reduz os conflitos de mobilidade existentes nas localidades. No caso do Brasil para que se tenha sucesso com implantação da técnica é preciso uma análise mais abrangente, articulada e ser passível de aplicação de forma completa, assim como ocorre nos países desenvolvidos.

  10. Traffic calming schemes : opportunities and implementation strategies.

    NARCIS (Netherlands)

    Schagen, I.N.L.G. van (ed.)

    2003-01-01

    Commissioned by the Swedish National Road Authority, this report aims to provide a concise overview of knowledge of and experiences with traffic calming schemes in urban areas, both on a technical level and on a policy level. Traffic calming refers to a combination of network planning and

  11. Calming Meditation Increases Altruism, Decreases Parochialism

    OpenAIRE

    Frost, Karl

    2017-01-01

    It has been proposed that cultivating calm will increase altruism and decrease parochialism, where altruism is defined as self-sacrifice in support of others, regardless of group affiliation or identity, and parochialism is defined as prosocial self-sacrifice restricted to fellow members of a group. Such could be the case with a calming meditation practice. An alternate hypothesis, coming from the study of ritual, proposes that shared practices lead to bonding, increasing parochialism, but no...

  12. Optimal control of motorsport differentials

    Science.gov (United States)

    Tremlett, A. J.; Massaro, M.; Purdy, D. J.; Velenis, E.; Assadian, F.; Moore, A. P.; Halley, M.

    2015-12-01

    Modern motorsport limited slip differentials (LSD) have evolved to become highly adjustable, allowing the torque bias that they generate to be tuned in the corner entry, apex and corner exit phases of typical on-track manoeuvres. The task of finding the optimal torque bias profile under such varied vehicle conditions is complex. This paper presents a nonlinear optimal control method which is used to find the minimum time optimal torque bias profile through a lane change manoeuvre. The results are compared to traditional open and fully locked differential strategies, in addition to considering related vehicle stability and agility metrics. An investigation into how the optimal torque bias profile changes with reduced track-tyre friction is also included in the analysis. The optimal LSD profile was shown to give a performance gain over its locked differential counterpart in key areas of the manoeuvre where a quick direction change is required. The methodology proposed can be used to find both optimal passive LSD characteristics and as the basis of a semi-active LSD control algorithm.

  13. Calming Children When Drawing Blood Using Breath-based Biofeedback

    OpenAIRE

    Sonne, T.; Merritt, T.; Marshall, P. E.; Lomholt, J.; Müller, J.; Grønbæk, K.

    2017-01-01

    Blood sampling is a common and necessary procedure in the treatment and diagnosis of a variety of diseases. However, it often results in painful and stressful experiences for children. Designed together with domain experts, ChillFish is a breath-controlled biofeedback game technology with bespoke airflow sensor that aims to calm children during blood sampling procedures. An experimental pilot study was conducted in which 20 children aged 6-11 were assigned to one of two conditions involving e...

  14. Canonical Wnt signaling in differentiated osteoblasts controls osteoclast differentiation.

    NARCIS (Netherlands)

    Glass, D.A.; Bialek, P.; Ahn, J.D.; Starbuck, M.; Patel, M.S.; Clevers, J.C.; Taketo, M.M.; Long, F.; McMahon, A.P.; Lang, R.A.; Karsenty, G.

    2005-01-01

    Inactivation of beta-catenin in mesenchymal progenitors prevents osteoblast differentiation; inactivation of Lrp5, a gene encoding a likely Wnt coreceptor, results in low bone mass (osteopenia) by decreasing bone formation. These observations indicate that Wnt signaling controls osteoblast

  15. Area-wide traffic calming for preventing traffic related injuries.

    Science.gov (United States)

    Bunn, F; Collier, T; Frost, C; Ker, K; Roberts, I; Wentz, R

    2003-01-01

    It is estimated that by 2020 road traffic crashes will have moved from ninth to third in the world disease burden ranking, as measured in disability adjusted life years, and second in developing countries. The identification of effective strategies for the prevention of traffic related injuries is of global health importance. Area-wide traffic calming schemes that discourage through traffic on residential roads is one such strategy. To evaluate the effectiveness of area-wide traffic calming in preventing traffic related crashes, injuries, and deaths. We searched the following electronic databases: Cochrane Injuries Group's Specialised Register, Cochrane Controlled Trials Register, MEDLINE, EMBASE and TRANSPORT (NTIS, TRIS, TRANSDOC). We searched the web sites of road safety organisations, handsearched conference proceedings, checked reference lists of relevant papers and contacted experts in the area. The search was not restricted by language or publication status. Randomised controlled trials, and controlled before-after studies of area-wide traffic calming schemes. Two reviewers independently extracted data on type of study, characteristics of intervention and control areas, and length of data collection periods. Before and after data were collected on the total number of road traffic crashes, all road user deaths and injuries, pedestrian-motor vehicle collisions and road user deaths. The statistical package STATA was used to calculate rate ratios for each study, which were then pooled to give an overall estimate using a random effects model. We found no randomised controlled trials, but 16 controlled before-after trials met our inclusion criteria. Seven studies were done in Germany, six in the UK, two in Australia and one in the Netherlands. There were no studies in low or middle income countries. Eight trials reported the number of road traffic crashes resulting in deaths. The pooled rate ratio was 0.63 (0.14, 2.59 95% CI). Sixteen studies reported the number

  16. Control synchronization of differential mobile robots

    NARCIS (Netherlands)

    Nijmeijer, H.; Rodriguez Angeles, A.; Allgoewer, F.

    2004-01-01

    In this paper a synchronization controller for differential mobile robots is proposed. The synchronization goal is to control the angular position of each wheel to a desired trajectory and at the same time the differential (or synchronization) error between the angular positions of the two wheels.

  17. Degenerated differential pair with controllable transconductance

    NARCIS (Netherlands)

    Mensink, Clemens; Mensink, Clemens H.J.; Nauta, Bram

    1998-01-01

    A differential pair with input transistors and provided with a variable degeneration resistor. The degeneration resistor comprises a series arrangement of two branches of coupled resistors which are shunted in mutually corresponding points by respective control transistors whose gates are

  18. Infinite Dimensional Differential Games with Hybrid Controls

    Indian Academy of Sciences (India)

    ... zero-sum infinite dimensional differential game of infinite duration with discounted payoff involving hybrid controls is studied. The minimizing player is allowed to take continuous, switching and impulse controls whereas the maximizing player is allowed to take continuous and switching controls. By taking strategies in the ...

  19. The effect of traffic calming on pedestrian injuries and motor vehicle ...

    African Journals Online (AJOL)

    predictable and preventable, while accidents are random, inevitable events. .... case-control study in an urban area in California found that the introduction of 1 600 ... of route to the school road and the year of construction of the traffic calming ...

  20. 78 FR 70907 - Implementation of the Commercial Advertisement Loudness Mitigation (CALM) Act

    Science.gov (United States)

    2013-11-27

    ... television industry can monitor and control the loudness level of digital TV programming. The rules took... references ITU-R BS.1770-3.''). As explained in the CALM Act Report and Order, the ITU-R BS.1770 measurement... includes improved guidance for measuring the loudness of surround programming in both its multichannel...

  1. [Herbs for calming liver and suppressing yang in treatment of hyperthyroidism with hyperactive liver yang: herbal effects on lymphocyte protein expression].

    Science.gov (United States)

    Li, Xiangping; Yin, Tao; Zhong, Guangwei; Li, Wei; Luo, Yanhong; Xiang, Lingli; Liu, Zhehao

    2011-07-01

    To observe the herbal effects on hyperthyroidism patients with syndrome of hyperactivity of liver-Yang by method for calming the liver and suppressing Yang and investigate its effects on the lymphocyte protein expression. This approach may lay a foundation for the further investigation of the curative mechanisms of calming the liver and suppressing Yang treatment. A total of 48 hyperthyroidism patients with syndrome of hyperactivity of liver-Yang were randomly divided into treatment group and control group. The treatment group was treated by method for calming the liver and suppressing Yang in accordance with traditional Chinese medicine (TCM) and the control group with thiamazole tablets for three periods of treatment The therapeutic effects, the score of TCM symptom, electrocardiogram (P wave), thyroid hormones and ultrasound were observed in both groups before and after the treatment. The side effects in the treatment course were observed in both groups. The level of differential protein expression was analyzed by two-dimensional electrphoresis and matrix assisted laser desorption/ionizaton time-of-flight mass spectrometry. The treatment group has the effect on stepping down the heart rate, cutting down the P wave amplitude changes, regulating the level of thyroid hormones and decreasing the volume of thyromegaly. There are not statistically significant between the treatment group and control group. However, the treatment group has obviously better effect on regulating TCM symptom and decreasing the side reaction than the control group (Peffective between the treatment group and control group. The average spots in lymphocyte for normal people, before and after treating hyperthyroidism patients with syndrome of hyperactivity of liver-Yang were (429 +/- 31), (452 +/- 28) and (437 +/- 36) spots respectively. Eight down-regulated protein expressions and 11 up-regulated protein expressions were obtained in the hyperthyroidism patients with syndrome of hyperactivity

  2. Control of differentiation of melanoma cells

    International Nuclear Information System (INIS)

    Eguchi, Goro

    1980-01-01

    To develop the method to induce the appearance of differentiation in amelanotic melanoma, experimental control of differentiation in B-16 melanoma cells of mice was discussed. Human melanoma cells and yellow melanin pigment cells useful for a fundamental study of radiotherapy for cancer were cultured and were differentiated into some lines. Melanotic B-16 cells and amelanotic B-16 cells were irradiated with thermal neutron (neutron: 2.7 x 10 12 , γ-dose: 32.3 rad) after they were cultured in culture solution containing 10 γ/ml of 10 B-dopa for 13 hours. A fine structure 5 hours after the irradiation in one of 5 experimental cases showed aggregated disintegration of melanin pigment particles, markedly deformed and fragmentized nucleus, and structural changes in cell membrane. (Tsunoda, M.)

  3. Circumpolar Active Layer Monitoring (CALM) Program Network, Version 1

    Data.gov (United States)

    National Aeronautics and Space Administration — The CALM network includes 168 active sites in both hemispheres with 15 participating countries. This network represents the only coordinated and standardized program...

  4. Calm temperament improves reproductive performance of beef cows.

    Science.gov (United States)

    Kasimanickam, R; Asay, M; Schroeder, S; Kasimanickam, V; Gay, J M; Kastelic, J P; Hall, J B; Whittier, W D

    2014-12-01

    Profitability of a beef operation is determined by the proportion of cows attaining pregnancy early in the breeding season and those that are pregnant at the end of breeding season. Many factors, including temperament, contribute to those reproductive parameters. The objective of this study was to evaluate effects of temperament on reproductive performance of beef cows. In Experiment 1, Angus and Angus-cross beef cows (n = 1546) from eight locations were assigned a body condition score (BCS; 1 = emaciated; 9 = obese) and chute exit and gait score (1 = slow exit, walk; calm temperament; 2 = jump, trot or run; excitable temperament). Cows were grouped with bulls (1 : 25 to 1 : 30; with satisfactory breeding potential and free of venereal disease) for an 85-day breeding season. Pregnancy status and stage of gestation were determined (transrectal palpation) 35 days after the end of the breeding season. Controlling for BCS (p score interaction (p scores for body condition and chute exit and gait (as described in Experiment 1) and assigned to bulls (breeding sound and free of venereal disease; 1 : 25 to 1 : 30) for 85 days. Pregnancy status was determined by transrectal palpation at 2 and 6 months after the onset of the breeding season. Controlling for BCS (p reproductive performance than calmer cows. The modified two-point chute exit-gait scoring method was repeatable and identified cattle with an excitable temperament. © 2014 Blackwell Verlag GmbH.

  5. The genetic network controlling plasma cell differentiation.

    Science.gov (United States)

    Nutt, Stephen L; Taubenheim, Nadine; Hasbold, Jhagvaral; Corcoran, Lynn M; Hodgkin, Philip D

    2011-10-01

    Upon activation by antigen, mature B cells undergo immunoglobulin class switch recombination and differentiate into antibody-secreting plasma cells, the endpoint of the B cell developmental lineage. Careful quantitation of these processes, which are stochastic, independent and strongly linked to the division history of the cell, has revealed that populations of B cells behave in a highly predictable manner. Considerable progress has also been made in the last few years in understanding the gene regulatory network that controls the B cell to plasma cell transition. The mutually exclusive transcriptomes of B cells and plasma cells are maintained by the antagonistic influences of two groups of transcription factors, those that maintain the B cell program, including Pax5, Bach2 and Bcl6, and those that promote and facilitate plasma cell differentiation, notably Irf4, Blimp1 and Xbp1. In this review, we discuss progress in the definition of both the transcriptional and cellular events occurring during late B cell differentiation, as integrating these two approaches is crucial to defining a regulatory network that faithfully reflects the stochastic features and complexity of the humoral immune response. 2011 Elsevier Ltd. All rights reserved.

  6. Traffic calming for the prevention of road traffic injuries: systematic review and meta-analysis.

    Science.gov (United States)

    Bunn, F; Collier, T; Frost, C; Ker, K; Roberts, I; Wentz, R

    2003-09-01

    To assess whether area-wide traffic calming schemes can reduce road crash related deaths and injuries. Systematic review and meta-analysis. Cochrane Injuries Group Specialised Register, Cochrane Central Register of Controlled Trials, Medline, EMBASE, Sociological Abstracts Science (and social science) citation index, National Technical Information service, Psychlit, Transport Research Information Service, International Road Research Documentation, and Transdoc, and web sites of road safety organisation were searched; experts were contacted, conference proceedings were handsearched, and relevant reference lists were checked. Randomised controlled trials, and controlled before/after studies of area-wide traffic calming schemes designed to discourage and slow down through traffic on residential roads. Data were collected on road user deaths, injuries, and traffic crashes. For each study rate ratios were calculated, the ratio of event rates before and after intervention in the traffic calmed area divided by the corresponding ratio of event rates in the control area, which were pooled to give an overall estimate using a random effects model. Sixteen controlled before/after studies met our inclusion criteria. Eight studies reported the number of road user deaths: pooled rate ratio 0.63 (95% confidence interval (CI) 0.14 to 2.59). Sixteen studies reported the number of injuries (fatal and non-fatal): pooled rate ratio 0.89 (95% CI 0.80 to 1.00). All studies were in high income countries. Area-wide traffic calming in towns and cities has the potential to reduce road traffic injuries. However, further rigorous evaluations of this intervention are needed, especially in low and middle income countries.

  7. Effects of a calm companion on fear reactions in naive test horses

    DEFF Research Database (Denmark)

    Christensen, Janne Winther; Malmkvist, Jens; Nielsen, Birte Lindstrøm

    2008-01-01

    : Minimally handled (n = 36), 2-year-old stallions were used, 18 as subjects and 18 as companions. Companion horses (n = 9) were habituated to an otherwise frightening, standardised test stimulus (calm companions), whereas the rest (n = 9) of the companion horses remained nonhabituated (control companions......). During the test, unique pairs of companion and subject horses were exposed to the test stimulus while heart rate and behavioural responses were registered. Subsequently, subject horses were exposed to the stimulus on their own (post test). Results: Subject horses, paired with a calm companion horse......, showed less fear-related behaviour and lower heart rate responses compared to subject horses with control companions. Results from the post test suggest that the difference between treatment groups remained in the subsequent absence of companion horses. Conclusions and potential relevance: It appears...

  8. Controllability of partial differential equations governed by multiplicative controls

    CERN Document Server

    Khapalov, Alexander Y

    2010-01-01

    The goal of this monograph is to address the issue of the global controllability of partial differential equations in the context of multiplicative (or bilinear) controls, which enter the model equations as coefficients. The mathematical models we examine include the linear and nonlinear parabolic and hyperbolic PDE's, the Schrödinger equation, and coupled hybrid nonlinear distributed parameter systems modeling the swimming phenomenon. The book offers a new, high-quality and intrinsically nonlinear methodology to approach the aforementioned highly nonlinear controllability problems.

  9. Novel Calmodulin (CALM2) Mutations Associated with Congenital Arrhythmia Susceptibility

    Science.gov (United States)

    Makita, Naomasa; Yagihara, Nobue; Crotti, Lia; Johnson, Christopher N.; Beckmann, Britt-Maria; Roh, Michelle S.; Shigemizu, Daichi; Lichtner, Peter; Ishikawa, Taisuke; Aiba, Takeshi; Homfray, Tessa; Behr, Elijah R.; Klug, Didier; Denjoy, Isabelle; Mastantuono, Elisa; Theisen, Daniel; Tsunoda, Tatsuhiko; Satake, Wataru; Toda, Tatsushi; Nakagawa, Hidewaki; Tsuji, Yukiomi; Tsuchiya, Takeshi; Yamamoto, Hirokazu; Miyamoto, Yoshihiro; Endo, Naoto; Kimura, Akinori; Ozaki, Kouichi; Motomura, Hideki; Suda, Kenji; Tanaka, Toshihiro; Schwartz, Peter J.; Meitinger, Thomas; Kääb, Stefan; Guicheney, Pascale; Shimizu, Wataru; Bhuiyan, Zahurul A.; Watanabe, Hiroshi; Chazin, Walter J.; George, Alfred L.

    2014-01-01

    Background Genetic predisposition to life-threatening cardiac arrhythmias such as in congenital long-QT syndrome (LQTS) and catecholaminergic polymorphic ventricular tachycardia (CPVT) represent treatable causes of sudden cardiac death in young adults and children. Recently, mutations in calmodulin (CALM1, CALM2) have been associated with severe forms of LQTS and CPVT, with life-threatening arrhythmias occurring very early in life. Additional mutation-positive cases are needed to discern genotype-phenotype correlations associated with calmodulin mutations. Methods and Results We employed conventional and next-generation sequencing approaches including exome analysis in genotype-negative LQTS probands. We identified five novel de novo missense mutations in CALM2 in three subjects with LQTS (p.N98S, p.N98I, p.D134H) and two subjects with clinical features of both LQTS and CPVT (p.D132E, p.Q136P). Age of onset of major symptoms (syncope or cardiac arrest) ranged from 1–9 years. Three of five probands had cardiac arrest and one of these subjects did not survive. Although all probands had LQTS, two subjects also exhibited electrocardiographic features consistent with CPVT. The clinical severity among subjects in this series was generally less than that originally reported for CALM1 and CALM2 associated with recurrent cardiac arrest during infancy. Four of five probands responded to β-blocker therapy whereas one subject with mutation p.Q136P died suddenly during exertion despite this treatment. Mutations affect conserved residues located within calcium binding loops III (p.N98S, p.N98I) or IV (p.D132E, p.D134H, p.Q136P) and caused reduced calcium binding affinity. Conclusions CALM2 mutations can be associated with LQTS and with overlapping features of LQTS and CPVT. PMID:24917665

  10. Speed-calming measures and their Effect on driving speed

    DEFF Research Database (Denmark)

    Agerholm, Niels; Knudsen, Daniel; Variyeswaran, Kajan

    2017-01-01

    Highlights •Speed humps and chicanes are widespread speed-calming measures. •Humps and chicanes have virtually the same reducing effect on mean speed. •Chicanes reduce speed variation less than humps and might therefore be a less safe measure....

  11. Optimal Control of Beer Fermentation Process Using Differential ...

    African Journals Online (AJOL)

    Optimal Control of Beer Fermentation Process Using Differential Transform Method. ... Journal of Applied Sciences and Environmental Management ... The method of differential transform was used to obtain the solution governing the fermentation process; the system of equation was transformed using the differential ...

  12. Nanotopographical Control of Stem Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Laura E. McNamara

    2010-01-01

    Full Text Available Stem cells have the capacity to differentiate into various lineages, and the ability to reliably direct stem cell fate determination would have tremendous potential for basic research and clinical therapy. Nanotopography provides a useful tool for guiding differentiation, as the features are more durable than surface chemistry and can be modified in size and shape to suit the desired application. In this paper, nanotopography is examined as a means to guide differentiation, and its application is described in the context of different subsets of stem cells, with a particular focus on skeletal (mesenchymal stem cells. To address the mechanistic basis underlying the topographical effects on stem cells, the likely contributions of indirect (biochemical signal-mediated and direct (force-mediated mechanotransduction are discussed. Data from proteomic research is also outlined in relation to topography-mediated fate determination, as this approach provides insight into the global molecular changes at the level of the functional effectors.

  13. A note on calm excited states of inflation

    International Nuclear Information System (INIS)

    Ashoorioon, Amjad; Shiu, Gary

    2011-01-01

    We identify a two-parameter family of excited states within slow-roll inflation for which either the corrections to the two-point function or the characteristic signatures of excited states in the three-point function — i.e. the enhancement for the flattened momenta configurations– are absent. These excited states may nonetheless violate the adiabaticity condition maximally. We dub these initial states of inflation calm excited states. We show that these two sets do not intersect, i.e., those that leave the power-spectrum invariant can be distinguished from their bispectra, and vice versa. The same set of calm excited states that leave the two-point function invariant for slow-roll inflation, do the same task for DBI inflation. However, at the level of three-point function, the calm excited states whose flattened configuration signature is absent for slow-roll inflation, will lead to an enhancement for DBI inflation generally, although the signature is smaller than what suggested by earlier analysis. This example also illustrates that imposing the Wronskian condition is important for obtaining a correct estimate of the non-Gaussian signatures

  14. Limited time perspective increases the value of calm.

    Science.gov (United States)

    Jiang, Da; Fung, Helene H; Sims, Tamara; Tsai, Jeanne L; Zhang, Fan

    2016-02-01

    Previous findings indirectly suggest that the more people perceive their time in life as limited, the more they value calm. No study, however, has directly tested this hypothesis. To this end, using a combination of survey, experience sampling, and experimental methods, we examined the relationship between future time perspective and the affective states that people ideally want to feel (i.e., their "ideal affect"). In Study 1, the more people reported a limited time perspective, the more they wanted to feel calm and experience other low-arousal positive states. In Study 2, participants were randomly assigned to a limited time or an expanded time condition. Participants in the limited time condition reported valuing calm and other low arousal positive states more than those in the expanded time condition. We discuss the implications of these findings for broadening our understanding of the factors that shape how people ideally want to feel, and their consequences for decision making. (c) 2016 APA, all rights reserved).

  15. Remaining Calm in the Midst of Chaos

    International Nuclear Information System (INIS)

    Sullivan, Robin S.; Ryan, Grant W.; Young, Jonathan

    2004-01-01

    At the DOE Hanford site in Washington State, Fluor Hanford, Inc is in the process of developing and, procuring systems to remove and disposition sludge from the 100 Area K Basins. The K Basins were used to store spent fuel from the operating reactors at the Hanford Site. The sludge is a by-product from th corrosion of the fuel and fuel storage canisters. The sludge removal project is very dynamic involving two basins, K East and K West, and has an ambitious schedule for removal and subsequent Basin D and D. The challenge for the safety basis development for this project is how to integrate the analysis with the project schedule and still provide the required project design, development, and regulatory (10CFR830) support. During the development of new project/systems, safety analysis activities are used throughout the design phase to assist in identifying design/safety issues before the design is complete. Control allocation and identification processes assist procurement of equipment during the development phase and a PDSA is required to support the decision to proceed with construction/installation. For the K Basins project, all the safety basis development activities need to be done in the context of new and existing facilities/equipment and an existing safety basis for the K Basins. When schedules are demanding and design, procurement, and safety documentation activities must be completed in parallel, it creates complex issues for maintaining the safety basis current. In addition, developing a safety basis that will cover the lifecycle of the facility creates issues when using it to support the necessary short term decisions at the same time as long term planning. Therefore, it was necessary to develop a safety basis strategy to deal with this situation. This paper discusses the strategy developed to deal with the complexity and project schedule issues and the methods for safety analysis development and documentation being used to assist in maintaining some

  16. Infinite dimensional differential games with hybrid controls

    Indian Academy of Sciences (India)

    The study of differential games with Elliott–Kalton strategies in the viscosity solution ... studied by Yong [6, 7]. ... Section 3 is devoted to the proof of the main uniqueness result for SQVI and the existence ...... Moreover, we have given explicit formulation of dynamic programming ... Financial support from NBHM is gratefully.

  17. Signal differentiation in position tracking control of dc motors

    International Nuclear Information System (INIS)

    Beltran-Carbajal, F; Valderrabano-Gonzalez, A; Rosas-Caro, J C

    2015-01-01

    An asymptotic differentiation approach with respect to time is used for on-line estimation of velocity and acceleration signals in controlled dc motors. The attractive feature of this differentiator of signals is that it does not require any system mathematical model, which allows its use in engineering systems that require the signal differentiation for its control, identification, fault detection, among other applications. Moreover, it is shown that the differentiation approach can be applied for output signals showing a chaotic behavior. In addition a differential flatness control scheme with additional integral compensation of the output error is proposed for tracking tasks of position reference trajectories for direct current electric motors using angular position measurements only

  18. approximate controllability of a non-autonomous differential equation

    Indian Academy of Sciences (India)

    53

    for a non-autonomous functional differential equation using the theory of linear ... approximate controllability of various functional differential equations in abstract ...... the operator A(t) and into the requirement that x(t) ∈ D(A) for all t ≥ 0.

  19. The eCALM Trial-eTherapy for cancer appLying mindfulness: online mindfulness-based cancer recovery program for underserved individuals living with cancer in Alberta: protocol development for a randomized wait-list controlled clinical trial

    Directory of Open Access Journals (Sweden)

    Zernicke Kristin A

    2013-02-01

    Full Text Available Abstract Background Elevated stress can exacerbate cancer symptom severity, and after completion of primary cancer treatments, many individuals continue to have significant distress. Mindfulness-Based Cancer Recovery (MBCR is an 8-week group psychosocial intervention consisting of training in mindfulness meditation and yoga designed to mitigate stress, pain, and chronic illness. Efficacy research shows face-to-face (F2F MBCR programs have positive benefits for cancer patients; however barriers exist that impede participation in F2F groups. While online MBCR groups are available to the public, none have been evaluated. Primary objective: determine whether underserved patients are willing to participate in and complete an online MBCR program. Secondary objectives: determine whether online MBCR will mirror previous efficacy findings from F2F MBCR groups on patient-reported outcomes. Method/design The study includes cancer patients in Alberta, exhibiting moderate distress, who do not have access to F2F MBCR. Participants will be randomized to either online MBCR, or waiting for the next available group. An anticipated sample size of 64 participants will complete measures online pre and post treatment or waiting period. Feasibility will be tracked through monitoring numbers eligible and participating through each stage of the protocol. Discussion 47 have completed/completing the intervention. Data suggest it is possible to conduct a randomized waitlist controlled trial of online MBCR to reach underserved cancer survivors. Trial registration Clinical Trials.gov Identifier: NCT01476891

  20. FHL2 interacts with CALM and is highly expressed in acute erythroid leukemia

    International Nuclear Information System (INIS)

    Pašaliç, Z; Greif, P A; Jurinoviç, V; Mulaw, M; Kakadia, P M; Tizazu, B; Fröhlich-Archangelo, L; Krause, A; Bohlander, S K

    2011-01-01

    The t(10;11)(p13;q14) translocation results in the fusion of the CALM (clathrin assembly lymphoid myeloid leukemia protein) and AF10 genes. This translocation is observed in acute myeloblastic leukemia (AML M6), acute lymphoblastic leukemia (ALL) and malignant lymphoma. Using a yeast two-hybrid screen, the four and a half LIM domain protein 2 (FHL2) was identified as a CALM interacting protein. Recently, high expression of FHL2 in breast, gastric, colon, lung as well as in prostate cancer was shown to be associated with an adverse prognosis. The interaction between CALM and FHL2 was confirmed by glutathione S-transferase-pulldown assay and co-immunoprecipitation experiments. The FHL2 interaction domain of CALM was mapped to amino acids 294–335 of CALM. The transcriptional activation capacity of FHL2 was reduced by CALM, but not by CALM/AF10, which suggests that regulation of FHL2 by CALM might be disturbed in CALM/AF10-positive leukemia. Extremely high expression of FHL2 was seen in acute erythroid leukemia (AML M6). FHL2 was also highly expressed in chronic myeloid leukemia and in AML with complex aberrant karyotype. These results suggest that FHL2 may play an important role in leukemogenesis, especially in the case of AML M6

  1. CIME course on Control of Partial Differential Equations

    CERN Document Server

    Alabau-Boussouira, Fatiha; Glass, Olivier; Le Rousseau, Jérôme; Zuazua, Enrique

    2012-01-01

    The term “control theory” refers to the body of results - theoretical, numerical and algorithmic - which have been developed to influence the evolution of the state of a given system in order to meet a prescribed performance criterion. Systems of interest to control theory may be of very different natures. This monograph is concerned with models that can be described by partial differential equations of evolution. It contains five major contributions and is connected to the CIME Course on Control of Partial Differential Equations that took place in Cetraro (CS, Italy), July 19 - 23, 2010.  Specifically, it covers the stabilization of evolution equations, control of the Liouville equation, control in fluid mechanics, control and numerics for the wave equation, and Carleman estimates for elliptic and parabolic equations with application to control. We are confident this work will provide an authoritative reference work for all scientists who are interested in this field, representing at the same time a fri...

  2. EMBEDDED CONTROL SYSTEM FOR MOBILE ROBOTS WITH DIFFERENTIAL DRIVE

    Directory of Open Access Journals (Sweden)

    Michal KOPČÍK

    2017-09-01

    Full Text Available This article deals with design and implementation of control system for mobile robots with differential drive using embedded system. This designed embedded system consists of single control board featuring ARM based microcontroller which control the peripherals in real time and perform all low-level motion control. Designed embedded system can be easily expanded with additional sensors, actuators or control units to enhance applicability of mobile robot. Designed embedded system also features build-in communication module, which can be used for data for data acquisition and control of the mobile robot. Control board was implemented on two different types of mobile robots with differential drive, one of which was wheeled and other was tracked. These mobile robots serve as testing platform for Fault Detection and Isolation using hardware and analytical redundancy using Multisensor Data Fusion based on Kalman filters.

  3. Global differential geometry: An introduction for control engineers

    Science.gov (United States)

    Doolin, B. F.; Martin, C. F.

    1982-01-01

    The basic concepts and terminology of modern global differential geometry are discussed as an introduction to the Lie theory of differential equations and to the role of Grassmannians in control systems analysis. To reach these topics, the fundamental notions of manifolds, tangent spaces, vector fields, and Lie algebras are discussed and exemplified. An appendix reviews such concepts needed for vector calculus as open and closed sets, compactness, continuity, and derivative. Although the content is mathematical, this is not a mathematical treatise but rather a text for engineers to understand geometric and nonlinear control.

  4. Self-induced drug intoxication in baclofen: of the calm hypotonic coma in the status epilepticus.

    Science.gov (United States)

    Thill, Chloé; Di Constanzo, Laurence; Pessey, François; Aries, Philippe; Montelescaut, Étienne; Sapin, Jeanne; Vaillant, Catherine; Drouillard, Isabelle

    2016-06-01

    Baclofen is an agonist of peripheral and central B gamma-aminobutyric acid receptors, whose activation causes a myorelaxation and a powerfull depression of the central nervous system. Moreover, it has an action against addiction, in reducing craving. Commercialized since 1975 in France, to control muscle spasticity due to medullar affection or multiple sclerosis, it receives a temporary recommendation of use in march 2014, as a last-line adjuvant treatment in alcohol withdrawal. Beyond its therapeutic use, baclofen is involved in many self-induced intoxications. We report the case of a patient who develops, after a massive ingestion of baclofen (supposed dose ingested: 1 200 mg), a hypotonic and calm coma, requiring her admission in our intensive care unit, and then a status epilepticus.

  5. Dissipative differential systems and the state space H∞ control problem

    NARCIS (Netherlands)

    Trentelman, H.L.; Willems, J.C.

    2000-01-01

    The purpose of this paper is to apply our very recent results on the synthesis of dissipative linear differential systems to the 'classical' state space H∞ control problem. We first review our general problem set-up, where the problem of rendering a given plant dissipative by general

  6. A differential-delay control for ramped magnet current

    Energy Technology Data Exchange (ETDEWEB)

    Murray, J. [State Univ. of New York, Stony Brook, NY (United States). Dept. of Electrical Engineering; Olsen, R. [Brookhaven National Lab., Upton, NY (United States)

    1992-11-01

    A differential-delay control system has been designed and implemented for the main dipole magnet power supply of the booster ring at the National Synchrotron Light Source at Brookhaven National Lab. The control algorithm was implemented on a floating-point digital signal processor; in tests, the use of digital signal-processing techniques gave a factor of ten improvement in the tracking response time, together with a modest improvement in tracking accuracy.

  7. A differential-delay control for ramped magnet current

    Energy Technology Data Exchange (ETDEWEB)

    Murray, J. (State Univ. of New York, Stony Brook, NY (United States). Dept. of Electrical Engineering); Olsen, R. (Brookhaven National Lab., Upton, NY (United States))

    1992-01-01

    A differential-delay control system has been designed and implemented for the main dipole magnet power supply of the booster ring at the National Synchrotron Light Source at Brookhaven National Lab. The control algorithm was implemented on a floating-point digital signal processor; in tests, the use of digital signal-processing techniques gave a factor of ten improvement in the tracking response time, together with a modest improvement in tracking accuracy.

  8. Optimal control in a model of malaria with differential susceptibility

    Science.gov (United States)

    Hincapié, Doracelly; Ospina, Juan

    2014-06-01

    A malaria model with differential susceptibility is analyzed using the optimal control technique. In the model the human population is classified as susceptible, infected and recovered. Susceptibility is assumed dependent on genetic, physiological, or social characteristics that vary between individuals. The model is described by a system of differential equations that relate the human and vector populations, so that the infection is transmitted to humans by vectors, and the infection is transmitted to vectors by humans. The model considered is analyzed using the optimal control method when the control consists in using of insecticide-treated nets and educational campaigns; and the optimality criterion is to minimize the number of infected humans, while keeping the cost as low as is possible. One first goal is to determine the effects of differential susceptibility in the proposed control mechanism; and the second goal is to determine the algebraic form of the basic reproductive number of the model. All computations are performed using computer algebra, specifically Maple. It is claimed that the analytical results obtained are important for the design and implementation of control measures for malaria. It is suggested some future investigations such as the application of the method to other vector-borne diseases such as dengue or yellow fever; and also it is suggested the possible application of free software of computer algebra like Maxima.

  9. Bistable switches control memory and plasticity in cellular differentiation

    Science.gov (United States)

    Wang, Lei; Walker, Brandon L.; Iannaccone, Stephen; Bhatt, Devang; Kennedy, Patrick J.; Tse, William T.

    2009-01-01

    Development of stem and progenitor cells into specialized tissues in multicellular organisms involves a series of cell fate decisions. Cellular differentiation in higher organisms is generally considered irreversible, and the idea of developmental plasticity in postnatal tissues is controversial. Here, we show that inhibition of mitogen-activated protein kinase (MAPK) in a human bone marrow stromal cell-derived myogenic subclone suppresses their myogenic ability and converts them into satellite cell-like precursors that respond to osteogenic stimulation. Clonal analysis of the induced osteogenic response reveals ultrasensitivity and an “all-or-none” behavior, hallmarks of a bistable switch mechanism with stochastic noise. The response demonstrates cellular memory, which is contingent on the accumulation of an intracellular factor and can be erased by factor dilution through cell divisions or inhibition of protein synthesis. The effect of MAPK inhibition also exhibits memory and appears to be controlled by another bistable switch further upstream that determines cell fate. Once the memory associated with osteogenic differentiation is erased, the cells regain their myogenic ability. These results support a model of cell fate decision in which a network of bistable switches controls inducible production of lineage-specific differentiation factors. A competitive balance between these factors determines cell fate. Our work underscores the dynamic nature of cellular differentiation and explains mechanistically the dual properties of stability and plasticity associated with the process. PMID:19366677

  10. Robust fast controller design via nonlinear fractional differential equations.

    Science.gov (United States)

    Zhou, Xi; Wei, Yiheng; Liang, Shu; Wang, Yong

    2017-07-01

    A new method for linear system controller design is proposed whereby the closed-loop system achieves both robustness and fast response. The robustness performance considered here means the damping ratio of closed-loop system can keep its desired value under system parameter perturbation, while the fast response, represented by rise time of system output, can be improved by tuning the controller parameter. We exploit techniques from both the nonlinear systems control and the fractional order systems control to derive a novel nonlinear fractional order controller. For theoretical analysis of the closed-loop system performance, two comparison theorems are developed for a class of fractional differential equations. Moreover, the rise time of the closed-loop system can be estimated, which facilitates our controller design to satisfy the fast response performance and maintain the robustness. Finally, numerical examples are given to illustrate the effectiveness of our methods. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

  11. Approximate Controllability for Linear Stochastic Differential Equations in Infinite Dimensions

    International Nuclear Information System (INIS)

    Goreac, D.

    2009-01-01

    The objective of the paper is to investigate the approximate controllability property of a linear stochastic control system with values in a separable real Hilbert space. In a first step we prove the existence and uniqueness for the solution of the dual linear backward stochastic differential equation. This equation has the particularity that in addition to an unbounded operator acting on the Y-component of the solution there is still another one acting on the Z-component. With the help of this dual equation we then deduce the duality between approximate controllability and observability. Finally, under the assumption that the unbounded operator acting on the state process of the forward equation is an infinitesimal generator of an exponentially stable semigroup, we show that the generalized Hautus test provides a necessary condition for the approximate controllability. The paper generalizes former results by Buckdahn, Quincampoix and Tessitore (Stochastic Partial Differential Equations and Applications, Series of Lecture Notes in Pure and Appl. Math., vol. 245, pp. 253-260, Chapman and Hall, London, 2006) and Goreac (Applied Analysis and Differential Equations, pp. 153-164, World Scientific, Singapore, 2007) from the finite dimensional to the infinite dimensional case

  12. Calming the mind: Healing after mass atrocity in Cambodia.

    Science.gov (United States)

    Agger, Inger

    2015-08-01

    After catastrophic events in which people's survival has been threatened, as happened during the Khmer Rouge regime in Cambodia 1975-1979, some continue to suffer from painful mental symptoms. Surveys carried out in Cambodia based on Western diagnostic categories have found a high prevalence of posttraumatic stress disorder (PTSD), depression, and anxiety symptoms in the population. This study explored Cambodian approaches to healing trauma, examining the ways in which Cambodians appeal to elements of Buddhism in their efforts to calm their minds, situating this mode of coping in the context of broader Khmer Buddhist practice and understandings. Western psychology may have much to learn from local, contextualised methods of dealing with the aftermath of trauma, including Khmer understandings of distress and approaches to relief. Methods of assessment and treatment of distress cannot be transposed wholesale from one cultural setting to another but require considerable cultural adaptation. This kind of cultural interchange may give rise to innovative, hybrid discourses and methods that may have much to offer in the support of victims of organised violence. © The Author(s) 2015.

  13. Calm Merino ewes have a higher ovulation rate and more multiple pregnancies than nervous ewes.

    Science.gov (United States)

    van Lier, E; Hart, K W; Viñoles, C; Paganoni, B; Blache, D

    2017-07-01

    In 1990, two selection lines of Merino sheep were established for low and high behavioural reactivity (calm and nervous temperament) at the University of Western Australia. Breeding records consistently showed that calm ewes weaned 10% to 19% more lambs than the nervous ewes. We hypothesise that calm ewes could have a higher ovulation rate than nervous ewes and/or calm ewes could have a lower rate of embryo mortality than nervous ewes. We tested these hypotheses by comparing the ovulation rate and the rate of embryo mortality between the calm and nervous lines before and after synchronisation and artificial insemination. Merino ewes from the temperament selection lines (calm, n=100; nervous, n=100) were synchronised (early breeding season) for artificial insemination (day 0) (intravaginal sponges containing fluogestone acetate and eCG immediately after sponge withdrawal). On day-17 and 11 ovarian cyclicity and corpora lutea, and on days 30 and 74 pregnancies and embryos/foetuses were determined by ultrasound. Progesterone, insulin and leptin concentrations were determined in blood plasma samples from days 5, 12 and 17. Ovarian cyclicity before and after oestrus synchronisation did not differ between the lines, but ovulation rate did (day-17: calm 1.63; nervous 1.26; Pewes was higher than on day-17. Loss of embryos by day 30 was high (calm: 71/150; nervous: 68/130); but nervous ewes had a lower proportion (15/47) of multiple pregnancies compared with calm ewes (30/46; Pewes had higher insulin (32.0 pmol/l±1.17 SEM; P=0.013) and lower leptin (1.18 μg/l±0.04 SEM; P=0.002) concentrations than calm ewes (insulin: 27.8 pmol/l±1.17 SEM; leptin: 1.35 μg/l±0.04 SEM). The differences in reproductive outcomes between the calm and nervous ewes were mainly due to a higher ovulation rate in calm ewes. We suggest that reproduction in nervous ewes is compromised by factors leading up to ovulation and conception, or the uterine environment during early pregnancy, that reflect

  14. Optimal Control Problems for Partial Differential Equations on Reticulated Domains

    CERN Document Server

    Kogut, Peter I

    2011-01-01

    In the development of optimal control, the complexity of the systems to which it is applied has increased significantly, becoming an issue in scientific computing. In order to carry out model-reduction on these systems, the authors of this work have developed a method based on asymptotic analysis. Moving from abstract explanations to examples and applications with a focus on structural network problems, they aim at combining techniques of homogenization and approximation. Optimal Control Problems for Partial Differential Equations on Reticulated Domains is an excellent reference tool for gradu

  15. Constrained Optimization and Optimal Control for Partial Differential Equations

    CERN Document Server

    Leugering, Günter; Griewank, Andreas

    2012-01-01

    This special volume focuses on optimization and control of processes governed by partial differential equations. The contributors are mostly participants of the DFG-priority program 1253: Optimization with PDE-constraints which is active since 2006. The book is organized in sections which cover almost the entire spectrum of modern research in this emerging field. Indeed, even though the field of optimal control and optimization for PDE-constrained problems has undergone a dramatic increase of interest during the last four decades, a full theory for nonlinear problems is still lacking. The cont

  16. Parallels between control PDE's (Partial Differential Equations) and systems of ODE's (Ordinary Differential Equations)

    Science.gov (United States)

    Hunt, L. R.; Villarreal, Ramiro

    1987-01-01

    System theorists understand that the same mathematical objects which determine controllability for nonlinear control systems of ordinary differential equations (ODEs) also determine hypoellipticity for linear partial differentail equations (PDEs). Moreover, almost any study of ODE systems begins with linear systems. It is remarkable that Hormander's paper on hypoellipticity of second order linear p.d.e.'s starts with equations due to Kolmogorov, which are shown to be analogous to the linear PDEs. Eigenvalue placement by state feedback for a controllable linear system can be paralleled for a Kolmogorov equation if an appropriate type of feedback is introduced. Results concerning transformations of nonlinear systems to linear systems are similar to results for transforming a linear PDE to a Kolmogorov equation.

  17. Developing a Measure of Traffic Calming Associated with Elementary School Students’ Active Transport

    OpenAIRE

    Nicholson, Lisa M.; Turner, Lindsey; Slater, Sandy J.; Abuzayd, Haytham; Chriqui, Jamie F.; Chaloupka, Frank

    2014-01-01

    The objective of this study is to develop a measure of traffic calming with nationally available GIS data from NAVTEQ and to validate the traffic calming index with the percentage of children reported by school administrators as walking or biking to school, using data from a nationally representative sample of elementary schools in 2006-2010. Specific models, with and without correlated errors, examined associations of objective GIS measures of the built environment, nationally available from...

  18. EZH2: a pivotal regulator in controlling cell differentiation.

    Science.gov (United States)

    Chen, Ya-Huey; Hung, Mien-Chie; Li, Long-Yuan

    2012-01-01

    Epigenetic regulation plays an important role in stem cell self-renewal, maintenance and lineage differentiation. The epigenetic profiles of stem cells are related to their transcriptional signature. Enhancer of Zeste homlog 2 (EZH2), a catalytic subunit of epigenetic regulator Polycomb repressive complex 2 (PRC2), has been shown to be a key regulator in controlling cellular differentiation. EZH2 is a histone methyltransferase that not only methylates histone H3 on Lys 27 (H3K27me3) but also interacts with and recruits DNA methyltransferases to methylate CpG at certain EZH2 target genes to establish firm repressive chromatin structures, contributing to tumor progression and the regulation of development and lineage commitment both in embryonic stem cells (ESCs) and adult stem cells. In addition to its well-recognized epigenetic gene silencing function, EZH2 also directly methylates nonhistone targets such as the cardiac transcription factor, GATA4, resulting in attenuated GATA4 transcriptional activity and gene repression. This review addresses recent progress toward the understanding of the biological functions and regulatory mechanisms of EZH2 and its targets as well as their roles in stem cell maintenance and cell differentiation.

  19. Chemo-mechanical control of neural stem cell differentiation

    Science.gov (United States)

    Geishecker, Emily R.

    Cellular processes such as adhesion, proliferation, and differentiation are controlled in part by cell interactions with the microenvironment. Cells can sense and respond to a variety of stimuli, including soluble and insoluble factors (such as proteins and small molecules) and externally applied mechanical stresses. Mechanical properties of the environment, such as substrate stiffness, have also been suggested to play an important role in cell processes. The roles of both biochemical and mechanical signaling in fate modification of stem cells have been explored independently. However, very few studies have been performed to study well-controlled chemo-mechanotransduction. The objective of this work is to design, synthesize, and characterize a chemo-mechanical substrate to encourage neuronal differentiation of C17.2 neural stem cells. In Chapter 2, Polyacrylamide (PA) gels of varying stiffnesses are functionalized with differing amounts of whole collagen to investigate the role of protein concentration in combination with substrate stiffness. As expected, neurons on the softest substrate were more in number and neuronal morphology than those on stiffer substrates. Neurons appeared locally aligned with an expansive network of neurites. Additional experiments would allow for statistical analysis to determine if and how collagen density impacts C17.2 differentiation in combination with substrate stiffness. Due to difficulties associated with whole protein approaches, a similar platform was developed using mixed adhesive peptides, derived from fibronectin and laminin, and is presented in Chapter 3. The matrix elasticity and peptide concentration can be individually modulated to systematically probe the effects of chemo-mechanical signaling on differentiation of C17.2 cells. Polyacrylamide gel stiffness was confirmed using rheological techniques and found to support values published by Yeung et al. [1]. Cellular growth and differentiation were assessed by cell counts

  20. A New Control Paradigm for Stochastic Differential Equations

    Science.gov (United States)

    Schmid, Matthias J. A.

    This study presents a novel comprehensive approach to the control of dynamic systems under uncertainty governed by stochastic differential equations (SDEs). Large Deviations (LD) techniques are employed to arrive at a control law for a large class of nonlinear systems minimizing sample path deviations. Thereby, a paradigm shift is suggested from point-in-time to sample path statistics on function spaces. A suitable formal control framework which leverages embedded Freidlin-Wentzell theory is proposed and described in detail. This includes the precise definition of the control objective and comprises an accurate discussion of the adaptation of the Freidlin-Wentzell theorem to the particular situation. The new control design is enabled by the transformation of an ill-posed control objective into a well-conditioned sequential optimization problem. A direct numerical solution process is presented using quadratic programming, but the emphasis is on the development of a closed-form expression reflecting the asymptotic deviation probability of a particular nominal path. This is identified as the key factor in the success of the new paradigm. An approach employing the second variation and the differential curvature of the effective action is suggested for small deviation channels leading to the Jacobi field of the rate function and the subsequently introduced Jacobi field performance measure. This closed-form solution is utilized in combination with the supplied parametrization of the objective space. For the first time, this allows for an LD based control design applicable to a large class of nonlinear systems. Thus, Minimum Large Deviations (MLD) control is effectively established in a comprehensive structured framework. The construction of the new paradigm is completed by an optimality proof for the Jacobi field performance measure, an interpretive discussion, and a suggestion for efficient implementation. The potential of the new approach is exhibited by its extension

  1. Chaos and its control in an impulsive differential system

    International Nuclear Information System (INIS)

    Jiang Guirong; Lu Qishao; Qian Linning

    2007-01-01

    In this paper, the existence of chaos and its control in an autonomous impulsive differential system are discussed both theoretically and numerically. The existence of a snap-back repeller, as well as the chaos in the sense of Li-Yorke, is proved based on the qualitative analysis using the Poincare map and the Lambert W-function. Moreover, the existence of the period-3 periodic window embedded in the chaotic region is also demonstrated. An algorithm of chaos control to stabilize the unstable periodic solutions is proposed. Detailed numerical results of chaotic attractors and stabilization of unstable periodic orbits by the impulsive effects, which are illustrated by an example, are in good agreement with the theoretical analysis

  2. Enhancing the Capacity of School Nurses to Reduce Excessive Anxiety in Children: Development of the CALM Intervention.

    Science.gov (United States)

    Drake, Kelly L; Stewart, Catherine E; Muggeo, Michela A; Ginsburg, Golda S

    2015-08-01

    Excessive anxiety is among the most common psychiatric problems facing youth. Because anxious youth tend to have somatic complaints, many seek help from the school nurse. Thus, school nurses are in an ideal position to provide early intervention. This study addresses this problem and describes the plans to develop and test a new intervention (Child Anxiety Learning Modules; CALM), delivered by school nurses, to reduce child anxiety and improve academic functioning. An iterative development process including consultation with an expert panel, two open trials, and a pilot randomized controlled study comparing CALM to usual care is proposed. Feedback will be solicited from all participants during each phase and data on outcome measures will be provided by children, parents, teachers, and independent evaluators. Data will be collected on intervention satisfaction and feasibility. Primary outcomes that include child anxiety symptoms, classroom behavior, and school performance (e.g., attendance, grades, standardized test scores) will be collected at pre- and post-interventions and at a 3-month follow-up evaluation. Pediatric anxiety is a common problem that school nurses frequently encounter. Consequently, they are well positioned to play a key role in enhancing access to behavioral health interventions to reduce anxiety and may therefore make a significant positive public health impact. © 2015 Wiley Periodicals, Inc.

  3. Developing a Web-Based Advisory Expert System for Implementing Traffic Calming Strategies

    Directory of Open Access Journals (Sweden)

    Amir Falamarzi

    2014-01-01

    Full Text Available Lack of traffic safety has become a serious issue in residential areas. In this paper, a web-based advisory expert system for the purpose of applying traffic calming strategies on residential streets is described because there currently lacks a structured framework for the implementation of such strategies. Developing an expert system can assist and advise engineers for dealing with traffic safety problems. This expert system is developed to fill the gap between the traffic safety experts and people who seek to employ traffic calming strategies including decision makers, engineers, and students. In order to build the expert system, examining sources related to traffic calming studies as well as interviewing with domain experts have been carried out. The system includes above 150 rules and 200 images for different types of measures. The system has three main functions including classifying traffic calming measures, prioritizing traffic calming strategies, and presenting solutions for different traffic safety problems. Verifying, validating processes, and comparing the system with similar works have shown that the system is consistent and acceptable for practical uses. Finally, some recommendations for improving the system are presented.

  4. Developing a Measure of Traffic Calming Associated with Elementary School Students’ Active Transport

    Science.gov (United States)

    Nicholson, Lisa M.; Turner, Lindsey; Slater, Sandy J.; Abuzayd, Haytham; Chriqui, Jamie F.; Chaloupka, Frank

    2014-01-01

    The objective of this study is to develop a measure of traffic calming with nationally available GIS data from NAVTEQ and to validate the traffic calming index with the percentage of children reported by school administrators as walking or biking to school, using data from a nationally representative sample of elementary schools in 2006-2010. Specific models, with and without correlated errors, examined associations of objective GIS measures of the built environment, nationally available from NAVTEQ, with the latent construct of traffic calming. The best fit model for the latent traffic calming construct was determined to be a five factor model including objective measures of intersection density, count of medians/dividers, count of low mobility streets, count of roundabouts, and count of on-street parking availability, with no correlated errors among items. This construct also proved to be a good fit for the full measurement model when the outcome measure of percentage of students walking or biking to school was added to the model. The traffic calming measure was strongly, significantly, and positively correlated with the percentage of students reported as walking or biking to school. Applicability of results to public health and transportation policies and practices are discussed. PMID:25506255

  5. Developing a Measure of Traffic Calming Associated with Elementary School Students' Active Transport.

    Science.gov (United States)

    Nicholson, Lisa M; Turner, Lindsey; Slater, Sandy J; Abuzayd, Haytham; Chriqui, Jamie F; Chaloupka, Frank

    2014-12-01

    The objective of this study is to develop a measure of traffic calming with nationally available GIS data from NAVTEQ and to validate the traffic calming index with the percentage of children reported by school administrators as walking or biking to school, using data from a nationally representative sample of elementary schools in 2006-2010. Specific models, with and without correlated errors, examined associations of objective GIS measures of the built environment, nationally available from NAVTEQ, with the latent construct of traffic calming. The best fit model for the latent traffic calming construct was determined to be a five factor model including objective measures of intersection density, count of medians/dividers, count of low mobility streets, count of roundabouts, and count of on-street parking availability, with no correlated errors among items. This construct also proved to be a good fit for the full measurement model when the outcome measure of percentage of students walking or biking to school was added to the model. The traffic calming measure was strongly, significantly, and positively correlated with the percentage of students reported as walking or biking to school. Applicability of results to public health and transportation policies and practices are discussed.

  6. Interleukin 4: signalling mechanisms and control of T cell differentiation.

    Science.gov (United States)

    Paul, W E

    1997-01-01

    Interleukin 4 (IL-4) is a pleiotropic type I cytokine that controls both growth and differentiation among haemopoietic and non-haemopoietic cells. Its receptor is a heterodimer. One chain, the IL-4R alpha chain, binds IL-4 with high affinity and determines the nature of the biochemical signals that are induced. The second chain, gamma c, is required for the induction of such signals. IL-4-mediated growth depends upon activation events that involve phosphorylation of Y497 of IL-4R alpha, leading to the binding and phosphorylation of 4PS/IRS-2 in haemopoietic cells and of IRS-1 in non-haemopoietic cells. By contrast, IL-4-mediated differentiation events depend upon more distal regions of the IL-4R alpha chain that include a series of STAT-6 binding sites. The distinctive roles of these receptor domains was verified by receptor-reconstruction experiments. The 'growth' and 'differentiation' domains of the IL-4R alpha chain, independently expressed as chimeric structures with a truncated version of the IL-2R beta chain, were shown to convey their functions to the hybrid receptor. The critical role of STAT-6 in IL-4-mediated gene activation and differentiation was made clear by the finding that lymphocytes from STAT-6 knockout mice are strikingly deficient in these functions but have retained the capacity to grow, at least partially, in response to IL-4. IL-4 plays a central role in determining the phenotype of naive CD4+ T cells. In the presence of IL-4, newly primed naive T cells develop into IL-4 producers while in its absence they preferentially become gamma-interferon (IFN-gamma) producers. Recently, a specialized subpopulation of T cells, CD4+/NK1.1+ cells, has been shown to produce large amounts of IL-4 upon stimulation. Two examples of mice with deficiencies in these cells are described--beta 2-microglobulin knockout mice and SJL mice. Both show defects in the development of IL-4-producing cells and in the increase in serum IgE in response to stimulation with the

  7. Preconditioning for partial differential equation constrained optimization with control constraints

    KAUST Repository

    Stoll, Martin; Wathen, Andy

    2011-01-01

    Optimal control problems with partial differential equations play an important role in many applications. The inclusion of bound constraints for the control poses a significant additional challenge for optimization methods. In this paper, we propose preconditioners for the saddle point problems that arise when a primal-dual active set method is used. We also show for this method that the same saddle point system can be derived when the method is considered as a semismooth Newton method. In addition, the projected gradient method can be employed to solve optimization problems with simple bounds, and we discuss the efficient solution of the linear systems in question. In the case when an acceleration technique is employed for the projected gradient method, this again yields a semismooth Newton method that is equivalent to the primal-dual active set method. We also consider the Moreau-Yosida regularization method for control constraints and efficient preconditioners for this technique. Numerical results illustrate the competitiveness of these approaches. © 2011 John Wiley & Sons, Ltd.

  8. Preconditioning for partial differential equation constrained optimization with control constraints

    KAUST Repository

    Stoll, Martin

    2011-10-18

    Optimal control problems with partial differential equations play an important role in many applications. The inclusion of bound constraints for the control poses a significant additional challenge for optimization methods. In this paper, we propose preconditioners for the saddle point problems that arise when a primal-dual active set method is used. We also show for this method that the same saddle point system can be derived when the method is considered as a semismooth Newton method. In addition, the projected gradient method can be employed to solve optimization problems with simple bounds, and we discuss the efficient solution of the linear systems in question. In the case when an acceleration technique is employed for the projected gradient method, this again yields a semismooth Newton method that is equivalent to the primal-dual active set method. We also consider the Moreau-Yosida regularization method for control constraints and efficient preconditioners for this technique. Numerical results illustrate the competitiveness of these approaches. © 2011 John Wiley & Sons, Ltd.

  9. ORCHIDS: an Observational Randomized Controlled Trial on Childhood Differential Susceptibility

    Directory of Open Access Journals (Sweden)

    Chhangur Rabia R

    2012-10-01

    Full Text Available Abstract Background A central tenet in developmental psychopathology is that childhood rearing experiences have a major impact on children’s development. Recently, candidate genes have been identified that may cause children to be differentially susceptible to these experiences (i.e., susceptibility genes. However, our understanding of the differential impact of parenting is limited at best. Specifically, more experimental research is needed. The ORCHIDS study will investigate gene-(gene-environment interactions to obtain more insight into a moderating effects of polymorphisms on the link between parenting and child behavior, and b behavioral mechanisms that underlie these gene-(gene-environment interactions in an experimental design. Methods/Design The ORCHIDS study is a randomized controlled trial, in which the environment will be manipulated with an intervention (i.e., Incredible Years parent training. In a screening, families with children aged 4–8 who show mild to (subclinical behavior problems will be targeted through community records via two Dutch regional healthcare organizations. Assessments in both the intervention and control condition will be conducted at baseline (i.e., pretest, after 6 months (i.e., posttest, and after 10 months (i.e., follow-up. Discussion This study protocol describes the design of a randomized controlled trial that investigates gene-(gene-environment interactions in the development of child behavior. Two hypotheses will be tested. First, we expect that children in the intervention condition who carry one or more susceptibility genes will show significantly lower levels of problem behavior and higher levels of prosocial behavior after their parent(s received the Incredible Years training, compared to children without these genes, or children in the control group. Second, we expect that children carrying one or more susceptibility genes will show a heightened sensitivity to changes in parenting behaviors, and

  10. Calm water resistance prediction of a bulk carrier using Reynolds averaged Navier-Stokes based solver

    Science.gov (United States)

    Rahaman, Md. Mashiur; Islam, Hafizul; Islam, Md. Tariqul; Khondoker, Md. Reaz Hasan

    2017-12-01

    Maneuverability and resistance prediction with suitable accuracy is essential for optimum ship design and propulsion power prediction. This paper aims at providing some of the maneuverability characteristics of a Japanese bulk carrier model, JBC in calm water using a computational fluid dynamics solver named SHIP Motion and OpenFOAM. The solvers are based on the Reynolds average Navier-Stokes method (RaNS) and solves structured grid using the Finite Volume Method (FVM). This paper comprises the numerical results of calm water test for the JBC model with available experimental results. The calm water test results include the total drag co-efficient, average sinkage, and trim data. Visualization data for pressure distribution on the hull surface and free water surface have also been included. The paper concludes that the presented solvers predict the resistance and maneuverability characteristics of the bulk carrier with reasonable accuracy utilizing minimum computational resources.

  11. Multistable decision switches for flexible control of epigenetic differentiation.

    Directory of Open Access Journals (Sweden)

    Raúl Guantes

    2008-11-01

    Full Text Available It is now recognized that molecular circuits with positive feedback can induce two different gene expression states (bistability under the very same cellular conditions. Whether, and how, cells make use of the coexistence of a larger number of stable states (multistability is however largely unknown. Here, we first examine how autoregulation, a common attribute of genetic master regulators, facilitates multistability in two-component circuits. A systematic exploration of these modules' parameter space reveals two classes of molecular switches, involving transitions in bistable (progression switches or multistable (decision switches regimes. We demonstrate the potential of decision switches for multifaceted stimulus processing, including strength, duration, and flexible discrimination. These tasks enhance response specificity, help to store short-term memories of recent signaling events, stabilize transient gene expression, and enable stochastic fate commitment. The relevance of these circuits is further supported by biological data, because we find them in numerous developmental scenarios. Indeed, many of the presented information-processing features of decision switches could ultimately demonstrate a more flexible control of epigenetic differentiation.

  12. Optimal Control of Beer Fermentation Process Using Differential ...

    African Journals Online (AJOL)

    ADOWIE PERE

    ABSTRACT: In this paper, the mathematical model of batch fermentation process of ethanol was formulated. The method of differential transform was used to obtain the solution governing the fermentation process; the system of equation was transformed using the differential transform method. The result obtained from the ...

  13. A tale of two cities: paradoxical intensity of traffic calming around Auckland schools.

    Science.gov (United States)

    Hopgood, Timothy; Percival, Teuila; Stewart, Joanna; Ameratunga, Shanthi

    2013-05-10

    The school journey is a common context for child pedestrian injuries in New Zealand, with children from low socioeconomic, Maori or Pacific families being at increased risk. The extent to which evidence-based environmental strategies that can address this problem are equitably implemented is unclear. To determine if there is a difference in the distribution of traffic-calming modifications around schools in areas of high and low socioeconomic deprivation in Auckland and Manukau Cities, New Zealand. From a list of the most and least socioeconomically deprived schools in Auckland and Manukau Cities, 40 of each were randomly selected. The number of modifications within a 1 km radius of these schools was recorded in December 2009 or January 2010. The association of deprivation and region with the numbers of traffic-calming modifications was examined using a general linear model. Socioeconomically least deprived schools had more traffic-calming interventions than the most deprived schools (least square mean (LSM): 25 versus 18; p=0.05), and Auckland schools had more interventions than Manukau schools (LSM: 27 versus 16; p=0.001). Traffic-calming measures were observed more commonly in less deprived areas where the risks of child pedestrian injuries are generally lower. This apparent paradox could result in increasing socioeconomic inequities in the distribution of child pedestrian injuries.

  14. Effects of scale and efficiency of rural traffic calming on safety, accessibility and wildlife

    NARCIS (Netherlands)

    Jaarsma, C.F.; Langevelde, van F.

    2011-01-01

    This paper examines the effects of scale and efficiency of regional traffic calming on traffic safety, rural accessibility, and survival of wildlife. We distinguish by the scale of road networks affected and considered the efficiencies of various bundling of traffic flows on designated routes.

  15. The Impact of Anxious and Calm Emotional States on Color Usage in Pre-Drawn Mandalas

    Science.gov (United States)

    Kersten, Andrea; van der Vennet, Renee

    2010-01-01

    The purpose of this single-subject experiment was to test whether a link exists between emotional state and color usage in a common art therapy technique. The researchers hypothesized that when coloring a pre-drawn mandala, participants would choose warm colors when they were anxious and cool colors when they were calm. The non-random sample…

  16. Traffic calming measures and their effect on the variation of speed

    Energy Technology Data Exchange (ETDEWEB)

    Gonzalo Orden, H.

    2016-07-01

    In recent years the number of deaths and serious injuries is decreasing in Spain, but, although the reduction outside the cities has been very strong, inside the urban areas, it has been smaller. This is especially hard if you look at the most vulnerable road users such as pedestrians and cyclists. In many accidents the speed factor appears closely linked not only to the number, but also to the severity of the accidents suffered inside the urban areas. Therefore, a reduction in the speed would improve the road safety. There are different measures known as {sup t}raffic calming measures{sup w}hose objectives are to reduce both the number and severity of accidents that occur on urban areas, by reducing the traffic flow through the streets, as well as the speed of the vehicles. However, the efficiency in speed reduction of each measure is not entirely known. That's the reason why they are implanted, in many cases, with no technical basis. The aim of this article is to show the effectiveness in reducing speed of some of the traffic calming measures. To this effect, field measurements were done on street sections with different types of traffic calming measures, in different places of a city of Burgos, in the north of Spain. These measurements were compared with other ones sited on other streets sections of similar characteristics but without traffic calming measures. Finally the conclusions are shown and some recommendations for improving their effectiveness are given. (Author)

  17. Encounter rates and swimming behavior of pause-travel and cruise larval fish predators in calm and turbulent laboratory environments

    DEFF Research Database (Denmark)

    MacKenzie, Brian; Kiørboe, Thomas

    1995-01-01

    measure of prey encounter rate in unsatiated larvae) were significantly higher in turbulent than in calm water at low food abundances for two size groups of cod. The difference in cod attack position rate between calm and turbulent water was much less when prey was more abundant. Attack position rates...... of herring larvae were higher in turbulent water than in calm water, but the difference was not significant. Interspecific differences in swimming and pausing behavior were related to differences in prey search strategy used by the two species (cod: pause-travel; herring: cruise). We used a newly developed...... search model for pause-travel predators in calm and turbulent environments to compare encounter rates for predators using cruise and pause-travel search strategies. Encounter rates for cod and herring larvae, estimated with respective search models, were similar in calm and low turbulence water; at high...

  18. Fractional order differentiation and robust control design crone, h-infinity and motion control

    CERN Document Server

    Sabatier, Jocelyn; Melchior, Pierre; Oustaloup, Alain

    2015-01-01

    This monograph collates the past decade’s work on fractional models and fractional systems in the fields of analysis, robust control and path tracking. Themes such as PID control, robust path tracking design and motion control methodologies involving fractional differentiation are amongst those explored. It juxtaposes recent theoretical results at the forefront in the field, and applications that can be used as exercises that will help the reader to assimilate the proposed methodologies. The first part of the book deals with fractional derivative and fractional model definitions, as well as recent results for stability analysis, fractional model physical interpretation, controllability, and H-infinity norm computation. It also presents a critical point of view on model pseudo-state and “real state”, tackling the problem of fractional model initialization. Readers will find coverage of PID, Fractional PID and robust control in the second part of the book, which rounds off with an extension of H-infinity ...

  19. Lymphoma and the control of B cell growth and differentiation.

    Science.gov (United States)

    Rui, Lixin; Goodnow, Christopher C

    2006-05-01

    It is now widely accepted that lymphomagenesis is a multistep transformation process. A number of genetic changes and environmental and infectious factors contributing to the development and malignant progression of B-cell lymphoproliferative disorders are well documented. Reciprocal chromosomal translocations involving the immunoglobulin loci are a hallmark of most mature B cell lymphomas and lead to dysregulated expression of proto-oncogenes (c-myc) important for cell proliferation or genes involved in cell cycle progression (cyclin D1), differentiation block (bcl-6, PAX5) and cell survival (bcl-2, NF-kappaB). In addition, genetic alterations that inactivate tumor suppressor genes (p53, p16) have been frequently detected in some lymphoma tissues. Many of these genes are normally regulated by signals from the B cell antigen receptor. The high prevalence of bacterial and viral infection in lymphoma patients supports the hypothesis that infectious agents may play a contributory role in the development and evolution of B cell lymphoproliferative disorders by either directly inducing polyclonal B cell hyperactivation (EBV, HCV), or providing a chronic antigenic stimulus (EBV, HCV, HBV, H. pylori), or mimicking B cell antigen receptor signaling (EBV, HCV, HHV8), although whether these are causative factors or they are secondary to genetic changes in lymphomagenesis remains to be defined. Stimulatory signals from reactive T cells, local cytokines and growth factors can also contribute, to some extent, to the progression of transformation. Modulation of B cell antigen receptor signaling therefore emerges as a potentially powerful strategy for controlling the growth of certain B cell lymphomas.

  20. Optimal Control Strategies in a Two Dimensional Differential Game Using Linear Equation under a Perturbed System

    Directory of Open Access Journals (Sweden)

    Musa Danjuma SHEHU

    2008-06-01

    Full Text Available This paper lays emphasis on formulation of two dimensional differential games via optimal control theory and consideration of control systems whose dynamics is described by a system of Ordinary Differential equation in the form of linear equation under the influence of two controls U(. and V(.. Base on this, strategies were constructed. Hence we determine the optimal strategy for a control say U(. under a perturbation generated by the second control V(. within a given manifold M.

  1. Connecting inventory control and repair shop control : a differentiated control structure for repairable spare parts

    NARCIS (Netherlands)

    Driessen, M.A.; Rustenburg, W.D.; Houtum, van G.J.J.A.N.; Wiers, V.C.S.

    2014-01-01

    This paper presents a control structure for integrating decisions on spare parts inventory control and the control of repair shops for maintenance spare parts. A dierentiated control structure is proposed for the various repair shop types recognized in practice. Decisions functions are mapped and

  2. Growth/differentiation factor-15 inhibits differentiation into osteoclasts - A novel factor involved in control of osteoclast differentiation

    Czech Academy of Sciences Publication Activity Database

    Vaňhara, P.; Lincová, Eva; Kozubík, Alois; Jurdic, P.; Souček, Karel; Šmarda, J.

    2009-01-01

    Roč. 78, č. 4 (2009), s. 213-222 ISSN 0301-4681 R&D Projects: GA ČR(CZ) GA204/07/0834 Grant - others:GA ČR(CZ) GA301/06/0036; GA ČR(CZ) GD204/08/H054; GA ČR(CZ) GA310/07/0961 Program:GA Institutional research plan: CEZ:AV0Z50040507; CEZ:AV0Z50040702 Keywords : osteoclast differentiation * GDF-15 * prostate cancer Subject RIV: BO - Biophysics Impact factor: 3.311, year: 2009

  3. Controllability Results For First Order Impulsive Stochastic Functional Differential Systems with State-Dependent Delay

    Directory of Open Access Journals (Sweden)

    C. Parthasarathy

    2013-03-01

    Full Text Available In this paper, we study the controllability results of first order impulsive stochastic differential and neutral differential systems with state-dependent delay by using semigroup theory. The controllability results are derived by the means of Leray-SchauderAlternative fixed point theorem. An example is provided to illustrate the theory.

  4. Epigenetic control of CD8+ T cell differentiation.

    Science.gov (United States)

    Henning, Amanda N; Roychoudhuri, Rahul; Restifo, Nicholas P

    2018-05-01

    Upon stimulation, small numbers of naive CD8 + T cells proliferate and differentiate into a variety of memory and effector cell types. CD8 + T cells can persist for years and kill tumour cells and virally infected cells. The functional and phenotypic changes that occur during CD8 + T cell differentiation are well characterized, but the epigenetic states that underlie these changes are incompletely understood. Here, we review the epigenetic processes that direct CD8 + T cell differentiation and function. We focus on epigenetic modification of DNA and associated histones at genes and their regulatory elements. We also describe structural changes in chromatin organization that affect gene expression. Finally, we examine the translational potential of epigenetic interventions to improve CD8 + T cell function in individuals with chronic infections and cancer.

  5. Retroviral insertional mutagenesis identifies Zeb2 activation as a novel leukemogenic collaborating event in CALM-AF10 transgenic mice.

    Science.gov (United States)

    Caudell, David; Harper, David P; Novak, Rachel L; Pierce, Rachel M; Slape, Christopher; Wolff, Linda; Aplan, Peter D

    2010-02-11

    The t(10;11) translocation results in a CALM-AF10 fusion gene in a subset of leukemia patients. Expression of a CALM-AF10 transgene results in leukemia, with prolonged latency and incomplete penetrance, suggesting that additional events are necessary for leukemic transformation. CALM-AF10 mice infected with the MOL4070LTR retrovirus developed acute leukemia, and ligation-mediated polymerase chain reaction was used to identify retroviral insertions at 19 common insertion sites, including Zeb2, Nf1, Mn1, Evi1, Ift57, Mpl, Plag1, Kras, Erg, Vav1, and Gata1. A total of 26% (11 of 42) of the mice had retroviral integrations near Zeb2, a transcriptional corepressor leading to overexpression of the Zeb2-transcript. A total of 91% (10 of 11) of mice with Zeb2 insertions developed B-lineage acute lymphoblastic leukemia, suggesting that Zeb2 activation promotes the transformation of CALM-AF10 hematopoietic precursors toward B-lineage leukemias. More than half of the mice with Zeb2 integrations also had Nf1 integrations, suggesting cooperativity among CALM-AF10, Zeb2, and Ras pathway mutations. We searched for Nras, Kras, and Ptpn11 point mutations in the CALM-AF10 leukemic mice. Three mutations were identified, all of which occurred in mice with Zeb2 integrations, consistent with the hypothesis that Zeb2 and Ras pathway activation promotes B-lineage leukemic transformation in concert with CALM-AF10.

  6. Electronic differential control of 2WD electric vehicle considering steering stability

    Science.gov (United States)

    Hua, Yiding; Jiang, Haobin; Geng, Guoqing

    2017-03-01

    Aiming at the steering wheel differential steering control technology of rear wheel independent driving electric wheel, considering the assisting effect of electronic differential control on vehicle steering, based on the high speed steering characteristic of electric wheel car, the electronic differential speed of auxiliary wheel steering is also studied. A yaw moment control strategy is applied to the vehicle at high speed. Based on the vehicle stability reference value, yaw rate is used to design the fuzzy controller to distribute the driving wheel torque. The simulation results show that the basic electronic differential speed function is realized based on the yaw moment control strategy, while the vehicle stability control is improved and the driving safety is enhanced. On the other hand, the torque control strategy can also assist steering of vehicle.

  7. Driving cycles for measuring passenger car emissions on roads with traffic calming measures

    International Nuclear Information System (INIS)

    Boulter, P.G.; Latham, S.; Ainge, M.

    1999-01-01

    Although local authorities in the UK need to be aware of any air quality impacts resulting from their traffic calming operations, there is little information relating to the effects of different traffic calming measures. The effects on air quality on this scale are complex, and so TRL is providing guidance by developing performance indices for different measures based on their effects on vehicle emissions. The emissions indices for passenger cars are based on tests conducted on a chassis dynamometer, and this paper describes the development of the methodology for constructing the driving cycles to be used. The technique involves the measurement of the speed profiles of a large number of vehicles using a roadside LIDAR system, and the determination of typical gear selections using three-instrumented cars

  8. Calming effect of orally administered γ-aminobutyric acid in Shih Tzu dogs.

    Science.gov (United States)

    Uetake, Katsuji; Okumoto, Ayano; Tani, Noriko; Goto, Akihiro; Tanaka, Toshio

    2012-12-01

    The calming effects of γ-aminobutyric acid (GABA) by oral administration were investigated in four adult Shih Tzu dogs. Three dosage levels (1, 2 and 4 mg/kg body weight) and non-administration were tested by an increase and decrease method. Changes in activity (for 1.5 h) and urinary cortisol levels (pre-administration, 3 and 7 h later) of dogs were monitored after administration. Without reference to dosage level, the mean times spent standing (P = 0.06), sitting (P level was observed at 7 h after administration (P GABA exerts calming effects on dogs as well as humans. © 2012 The Authors. Animal Science Journal © 2012 Japanese Society of Animal Science.

  9. A Method for Traffic Calming Using Radio Transmitter

    Directory of Open Access Journals (Sweden)

    Amin Mirza Boroujerdian

    2017-01-01

    Full Text Available Excessive speed is one of the major factors in transportation safety assessment and is influenced by road geometric design, vehicle properties, and driving pattern. Exploiting innovative methods along with the conventional ones has been proven to be effective in road safety to control the speed limit. In this study, a supplementary tool is introduced to help drivers to observe the speed limit. In line with this objective, the effectiveness of Voice Sign System (VSS as an Intelligent Transportation System is evaluated. In order to measure the speed, video processing software is used. Moreover, SPSS is utilized to perform statistical analysis and compare upstream and downstream speeds before and after a message transmission. The study is conducted in Yadegar-e-Imam expressway, located in Tehran, to evaluate the effectiveness of a voice message. The message reads as follows: “Observe the Speed Limit.” The results reveal that VSS is an effective tool for speed reduction as well as the speed limit observation in expressways. The study shows that the speed is reduced by 18% on average, and speed limit observation is improved by 46.5%, out of which 18.2% is direct and 28.3% is indirect influence of VSS.

  10. Development of a Child Abuse Level Management (CALM) Guide for Research with Young Children.

    Science.gov (United States)

    Lewin, Linda C; Schim, Stephanie Myers

    2016-05-01

    Reporting child abuse or neglect is an ethical expectation and a legislated mandate of behavioral and health care professionals in the United States. In particular, researchers who investigate parent-child dyads are responsible for submitting procedures and informed consent documents to institutional review boards that provide for the protection of children. The challenge for researchers is to recognize failing quality of parent-child interaction, prior to any event of maltreatment and to intercede in a deteriorating dynamic. The obligation to report any suspicions of child maltreatment supersedes the responsibility to provide for confidentiality of research data. The purpose of this paper is to describe the rationale for the development of a research protocol guide, Child Abuse Level Management (CALM), and address protection of children in research. The CALM is a brief, flexible guide designed for use by researchers to help identify and respond to negative trends in the parent-child interaction during data collection. Suggested intervention scripts are provided that can be modified for specific culture-focused samples. The CALM guide can be used for training of data collectors using simulations prior to initiating any study involving higher-risk dyads. Copyright © 2015 Elsevier Inc. All rights reserved.

  11. Impact of Perceptual Speed Calming Curve Countermeasures on Drivers’ Anticipation and Mitigation Ability : A Driving Simulator Study

    Science.gov (United States)

    2018-02-01

    Horizontal curves are unavoidable in rural roads and are a serious crash risk to vehicle occupants. This study investigates the impact and effectiveness of three curve-based perceptual speed-calming countermeasures (advance curve warning signs, chevr...

  12. New trajectory-driven aerosol and chemical process model Chemical and Aerosol Lagrangian Model (CALM

    Directory of Open Access Journals (Sweden)

    P. Tunved

    2010-11-01

    Full Text Available A new Chemical and Aerosol Lagrangian Model (CALM has been developed and tested. The model incorporates all central aerosol dynamical processes, from nucleation, condensation, coagulation and deposition to cloud formation and in-cloud processing. The model is tested and evaluated against observations performed at the SMEAR II station located at Hyytiälä (61° 51' N, 24° 17' E over a time period of two years, 2000–2001. The model shows good agreement with measurements throughout most of the year, but fails in reproducing the aerosol properties during the winter season, resulting in poor agreement between model and measurements especially during December–January. Nevertheless, through the rest of the year both trends and magnitude of modal concentrations show good agreement with observation, as do the monthly average size distribution properties. The model is also shown to capture individual nucleation events to a certain degree. This indicates that nucleation largely is controlled by the availability of nucleating material (as prescribed by the [H2SO4], availability of condensing material (in this model 15% of primary reactions of monoterpenes (MT are assumed to produce low volatile species and the properties of the size distribution (more specifically, the condensation sink. This is further demonstrated by the fact that the model captures the annual trend in nuclei mode concentration. The model is also used, alongside sensitivity tests, to examine which processes dominate the aerosol size distribution physical properties. It is shown, in agreement with previous studies, that nucleation governs the number concentration during transport from clean areas. It is also shown that primary number emissions almost exclusively govern the CN concentration when air from Central Europe is advected north over Scandinavia. We also show that biogenic emissions have a large influence on the amount of potential CCN observed

  13. Role of hormones in controlling vascular differentiation and the mechanism of lateral root initiation.

    Science.gov (United States)

    Aloni, Roni

    2013-11-01

    The vascular system in plants is induced and controlled by streams of inductive hormonal signals. Auxin produced in young leaves is the primary controlling signal in vascular differentiation. Its polar and non-polar transport pathways and major controlling mechanisms are clarified. Ethylene produced in differentiating protoxylem vessels is the signal that triggers lateral root initiation, while tumor-induced ethylene is a limiting and controlling factor of crown gall development and its vascular differentiation. Gibberellin produced in mature leaves moves non-polarly and promotes elongation, regulates cambium activity and induces long fibers. Cytokinin from the root cap moves upward to promote cambial activity and stimulate shoot growth and branching, while strigolactone from the root inhibits branching. Furthermore, the role of the hormonal signals in controlling the type of differentiating vascular elements and gradients of conduit size and density, and how they regulate plant adaptation and have shaped wood evolution are elucidated.

  14. Nonlinear control and filtering using differential flatness approaches applications to electromechanical systems

    CERN Document Server

    Rigatos, Gerasimos G

    2015-01-01

    This monograph presents recent advances in differential flatness theory and analyzes its use for nonlinear control and estimation. It shows how differential flatness theory can provide solutions to complicated control problems, such as those appearing in highly nonlinear multivariable systems and distributed-parameter systems. Furthermore, it shows that differential flatness theory makes it possible to perform filtering and state estimation for a wide class of nonlinear dynamical systems and provides several descriptive test cases. The book focuses on the design of nonlinear adaptive controllers and nonlinear filters, using exact linearization based on differential flatness theory. The adaptive controllers obtained can be applied to a wide class of nonlinear systems with unknown dynamics, and assure reliable functioning of the control loop under uncertainty and varying operating conditions. The filters obtained outperform other nonlinear filters in terms of accuracy of estimation and computation speed. The bo...

  15. Linear-quadratic control and quadratic differential forms for multidimensional behaviors

    NARCIS (Netherlands)

    Napp, D.; Trentelman, H.L.

    2011-01-01

    This paper deals with systems described by constant coefficient linear partial differential equations (nD-systems) from a behavioral point of view. In this context we treat the linear-quadratic control problem where the performance functional is the integral of a quadratic differential form. We look

  16. Stability and control of Lur'e-type measure differential inclusions

    NARCIS (Netherlands)

    Wouw, van de N.; Leine, R.I.; Leonov, G.; Nijmeijer, H.; Pogromsky, A.; Fradkov, A.

    2010-01-01

    In this paper we present results on, firstly, the stability analysis for perturbed Lur'e-type measure differential inclusions and, secondly, the tracking control problem for this class of systems. The framework of measure differential inclusions allows us to describe systems with discontinuities in

  17. Genetic control of differential acetylation in diabetic rats.

    Directory of Open Access Journals (Sweden)

    Pamela J Kaisaki

    Full Text Available Post-translational protein modifications such as acetylation have significant regulatory roles in metabolic processes, but their relationship to both variation in gene expression and DNA sequence is unclear. We address this question in the Goto-Kakizaki (GK rat inbred strain, a model of polygenic type 2 diabetes. Expression of the NAD-dependent deacetylase Sirtuin-3 is down-regulated in GK rats compared to normoglycemic Brown Norway (BN rats. We show first that a promoter SNP causes down-regulation of Sirtuin-3 expression in GK rats. We then use mass-spectrometry to identify proteome-wide differential lysine acetylation of putative Sirtuin-3 protein targets in livers of GK and BN rats. These include many proteins in pathways connected to diabetes and metabolic syndrome. We finally sequence GK and BN liver transcriptomes and find that mRNA expression of these targets does not differ significantly between GK and BN rats, in contrast to other components of the same pathways. We conclude that physiological differences between GK and BN rats are mediated by a combination of differential protein acetylation and gene transcription and that genetic variation can modulate acetylation independently of expression.

  18. Effect of tight control management on Crohn's disease (CALM): a multicentre, randomised, controlled phase 3 trial

    NARCIS (Netherlands)

    Colombel, Jean-Frederic; Panaccione, Remo; Bossuyt, Peter; Lukas, Milan; Baert, Filip; Vaňásek, Tomas; Danalioglu, Ahmet; Novacek, Gottfried; Armuzzi, Alessandro; Hébuterne, Xavier; Travis, Simon; Danese, Silvio; Reinisch, Walter; Sandborn, William J.; Rutgeerts, Paul; Hommes, Daniel; Schreiber, Stefan; Neimark, Ezequiel; Huang, Bidan; Zhou, Qian; Mendez, Paloma; Petersson, Joel; Wallace, Kori; Robinson, Anne M.; Thakkar, Roopal B.; D'Haens, Geert

    2018-01-01

    Biomarkers of intestinal inflammation, such as faecal calprotectin and C-reactive protein, have been recommended for monitoring patients with Crohn's disease, but whether their use in treatment decisions improves outcomes is unknown. We aimed to compare endoscopic and clinical outcomes in patients

  19. Small-Signal Modeling and Analysis of Grid-Connected Inverter with Power Differential Droop Control

    Directory of Open Access Journals (Sweden)

    Xin Chen

    2016-01-01

    Full Text Available The conventional voltage and frequency droop control strategy in grid-connected inverter suffers a major setback in the presence of disturbance by producing oscillations. Adding a power differential term in droop controller is an effective way to address such drawback. In this paper, grid-connected inverter’s small-signal models of the conventional droop control and the power differential droop control are established. The eigenvalues of the models are then determined by system matrix. The eigenvalues analysis is presented which helps in identifying the relationship between the system stability and controller parameters. It is concluded that the damping ratio of dominant low-frequency eigenvalues increased and the oscillation caused by the disturbance is suppressed when a power differential term is added to the droop control method. The MATLAB/Simulink models of grid-connected inverter with both control strategies are also established to validate the results of small-signal analysis.

  20. Controllability and Stabilization of Bilinear and Semilinear Partial Differential Equations

    DEFF Research Database (Denmark)

    Krishnaswamy, Vijayaraghavan

    The topic of the thesis is the investigation of the question of controllability of weakly nonlinear partial differntial equations. The method is based on the Hilbert Uniqueness Method.......The topic of the thesis is the investigation of the question of controllability of weakly nonlinear partial differntial equations. The method is based on the Hilbert Uniqueness Method....

  1. Control of exoenzyme production, motility and cell differentiation in Serratia liquefaciens

    DEFF Research Database (Denmark)

    Givskov, Michael Christian; Eberl, Leo; Molin, Søren

    1997-01-01

    Serratia liquefaciens secretes a broad spectrum of hydrolytic enzymes to the surrounding medium and possesses the ability to differentiate into specialized swarmer cells capable of rapid surface motility. Control of exoenzyme production and swarming motility is governed by similar regulatory...

  2. Controllability of impulsive neutral functional differential inclusions with infinite delay in Banach spaces

    International Nuclear Information System (INIS)

    Chang, Y.-K.; Anguraj, A.; Mallika Arjunan, M.

    2009-01-01

    In this work, we establish a sufficient condition for the controllability of the first-order impulsive neutral functional differential inclusions with infinite delay in Banach spaces. The results are obtained by using the Dhage's fixed point theorem.

  3. Low-bias negative differential conductance controlled by electrode separation

    Science.gov (United States)

    Yi, Xiao-Hua; Liu, Ran; Bi, Jun-Jie; Jiao, Yang; Wang, Chuan-Kui; Li, Zong-Liang

    2016-12-01

    The electronic transport properties of a single thiolated arylethynylene molecule with 9,10-dihydroanthracene core, denoted as TADHA, is studied by using non-equilibrium Green’s function formalism combined with ab initio calculations. The numerical results show that the TADHA molecule exhibits excellent negative differential conductance (NDC) behavior at lower bias regime as probed experimentally. The NDC behavior of TADHA molecule originates from the Stark effect of the applied bias voltage, by which the highest occupied molecular orbital (HOMO) and the HOMO-1 are pulled apart and become localized. The NDC behavior of TADHA molecular system is tunable by changing the electrode distance. Shortening the electrode separation can enhance the NDC effect which is attributed to the possible increase of coupling between the two branches of TADHA molecule. Project supported by the National Natural Science Foundation of China (Grant Nos. 11374195 and 11405098) and the Natural Science Foundation of Shandong Province, China (Grant No. ZR2013FM006).

  4. Low-bias negative differential conductance controlled by electrode separation

    International Nuclear Information System (INIS)

    Yi Xiao-Hua; Liu Ran; Bi Jun-Jie; Jiao Yang; Wang Chuan-Kui; Li Zong-Liang

    2016-01-01

    The electronic transport properties of a single thiolated arylethynylene molecule with 9,10-dihydroanthracene core, denoted as TADHA, is studied by using non-equilibrium Green’s function formalism combined with ab initio calculations. The numerical results show that the TADHA molecule exhibits excellent negative differential conductance (NDC) behavior at lower bias regime as probed experimentally. The NDC behavior of TADHA molecule originates from the Stark effect of the applied bias voltage, by which the highest occupied molecular orbital (HOMO) and the HOMO-1 are pulled apart and become localized. The NDC behavior of TADHA molecular system is tunable by changing the electrode distance. Shortening the electrode separation can enhance the NDC effect which is attributed to the possible increase of coupling between the two branches of TADHA molecule. (paper)

  5. The Him gene reveals a balance of inputs controlling muscle differentiation in Drosophila.

    Science.gov (United States)

    Liotta, David; Han, Jun; Elgar, Stuart; Garvey, Clare; Han, Zhe; Taylor, Michael V

    2007-08-21

    Tissue development requires the controlled regulation of cell-differentiation programs. In muscle, the Mef2 transcription factor binds to and activates the expression of many genes and has a major positive role in the orchestration of differentiation. However, little is known about how Mef2 activity is regulated in vivo during development. Here, we characterize a gene, Holes in muscle (Him), which our results indicate is part of this control in Drosophila. Him expression rapidly declines as embryonic muscle differentiates, and consistent with this, Him overexpression inhibits muscle differentiation. This inhibitory effect is suppressed by mef2, implicating Him in the mef2 pathway. We then found that Him downregulates the transcriptional activity of Mef2 in both cell culture and in vivo. Furthermore, Him protein binds Groucho, a conserved, transcriptional corepressor, through a WRPW motif and requires this motif and groucho function to inhibit both muscle differentiation and Mef2 activity during development. Together, our results identify a mechanism that can inhibit muscle differentiation in vivo. We conclude that a balance of positive and negative inputs, including Mef2, Him, and Groucho, controls muscle differentiation during Drosophila development and suggest that one outcome is to hold developing muscle cells in a state with differentiation genes poised to be expressed.

  6. N-Player Stochastic Differential Games. [control theory

    Science.gov (United States)

    Varaiya, P.

    1974-01-01

    Conditions are described which guarantee that the control strategies adopted by N players constitute an efficient solution, an equilibrium, or a core solution. The system dynamics are described by an Ito equation, and all players have perfect information. It was found that when the set of instantaneous joint costs and velocity vectors is convex, the conditions are necessary.

  7. Clinical leadership in mental health nursing: the importance of a calm and confident approach.

    Science.gov (United States)

    Ennis, Gary; Happell, Brenda; Reid-Searl, Kerry

    2015-01-01

    Explore the perceptions of nurses working in mental health of effective clinical leadership. In-depth interviews were conducted with registered nurses employed in a mental health setting. Qualitative research using grounded theory. Remaining calm and confident in times of crisis and uncertainty was identified as one attribute of clinical leadership. Participants noted clinical leaders' demeanor during stressful or crisis situations, and their ability to manage unpredictable or unexpected clinical situations as contributing positively to clinical practice. Understanding these characteristics and how they can influence positive outcomes for clients is crucial in addressing the recruitment and retention challenges for the nursing workforce. © 2014 Wiley Periodicals, Inc.

  8. Activation of the Ca2+/calcineurin/NFAT2 pathway controls smooth muscle cell differentiation

    International Nuclear Information System (INIS)

    Larrieu, Daniel; Thiebaud, Pierre; Duplaa, Cecile; Sibon, Igor; Theze, Nadine; Lamaziere, Jean-Marie Daniel

    2005-01-01

    Cellular mechanisms controlling smooth muscle cells (SMCs) phenotypic modulation are largely unknown. Intracellular Ca 2+ movements are essential to ensure SMC functions; one of the roles of Ca 2+ is to regulate calcineurin, which in turn induces nuclear localization of the nuclear factor of activated T-cell (NFAT). In order to investigate, during phenotypic differentiation of SMCs, the effect of calcineurin inhibition on NFAT 2 nuclear translocation, we used a culture model of SMC differentiation in serum-free conditions. We show that the treatment of cultured SMC with the calcineurin inhibitor cyclosporine A induced their dedifferentiation while preventing their differentiation. These findings suggest that nuclear translocation of NFAT 2 is dependent of calcineurin activity during the in vitro SMC differentiation kinetic and that the nuclear presence of NFAT 2 is critical in the acquisition and maintenance of SMC differentiation

  9. State-dependent differential Riccati equation to track control of time-varying systems with state and control nonlinearities.

    Science.gov (United States)

    Korayem, M H; Nekoo, S R

    2015-07-01

    This work studies an optimal control problem using the state-dependent Riccati equation (SDRE) in differential form to track for time-varying systems with state and control nonlinearities. The trajectory tracking structure provides two nonlinear differential equations: the state-dependent differential Riccati equation (SDDRE) and the feed-forward differential equation. The independence of the governing equations and stability of the controller are proven along the trajectory using the Lyapunov approach. Backward integration (BI) is capable of solving the equations as a numerical solution; however, the forward solution methods require the closed-form solution to fulfill the task. A closed-form solution is introduced for SDDRE, but the feed-forward differential equation has not yet been obtained. Different ways of solving the problem are expressed and analyzed. These include BI, closed-form solution with corrective assumption, approximate solution, and forward integration. Application of the tracking problem is investigated to control robotic manipulators possessing rigid or flexible joints. The intention is to release a general program for automatic implementation of an SDDRE controller for any manipulator that obeys the Denavit-Hartenberg (D-H) principle when only D-H parameters are received as input data. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

  10. Gametophyte differentiation and imprinting control in plants: Crosstalk between RBR and chromatin.

    Science.gov (United States)

    Johnston, Amal J; Gruissem, Wilhelm

    2009-01-01

    The Retinoblastoma (pRb) pathway has been implicated as a convergent regulatory unit in the control of cell cycle and disease. We have shown that a crosstalk between RETINOBLASTOMA RELATED (RBR), the Arabidopsis homologue of pRb, and the genes encoding proteins of the chromatin complexes involved in DNA or histone methylation, controls gametophytic and post-fertilization differentiation events and a subset of imprinting effects. We describe here a plausible model that incorporates several components of the plant Retinoblastoma pathway, thus offering a novel paradigm that merges the traditional cell cycle and the chromatin components in the control of cell differentiation and imprinting.

  11. Mobile point sensors and actuators in the controllability theory of partial differential equations

    CERN Document Server

    Khapalov, Alexander Y

    2017-01-01

    This book presents a concise study of controllability theory of partial differential equations when they are equipped with actuators and/or sensors that are finite dimensional at every moment of time. Based on the author’s extensive research in the area of controllability theory, this monograph specifically focuses on the issues of controllability, observability, and stabilizability for parabolic and hyperbolic partial differential equations. The topics in this book also cover related applied questions such as the problem of localization of unknown pollution sources based on information obtained from point sensors that arise in environmental monitoring. Researchers and graduate students interested in controllability theory of partial differential equations and its applications will find this book to be an invaluable resource to their studies.

  12. Implementation of Wavelet-Based Robust Differential Control for Electric Vehicle Application

    DEFF Research Database (Denmark)

    Daya, Febin; Padmanaban, Sanjeevikumar; Blaabjerg, Frede

    2015-01-01

    This research letter presents the modeling and simulation of electronic differential, employing a novel wavelet controller for two brushless dc motors. The proposed controller uses discrete wavelet transform to decompose the error between actual and reference speed. Error signal that is actually...

  13. Planar Cell Polarity Controls Pancreatic Beta Cell Differentiation and Glucose Homeostasis

    DEFF Research Database (Denmark)

    Cortijo, Cedric; Gouzi, Mathieu; Tissir, Fadel

    2012-01-01

    glucose clearance. Loss of Celsr2 and 3 leads to a reduction of Jun phosphorylation in progenitors, which, in turn, reduces beta cell differentiation from endocrine progenitors. These results highlight the importance of the PCP pathway in cell differentiation in vertebrates. In addition, they reveal.......5 synchronously to apicobasal polarization of pancreas progenitors. Loss of function of the two PCP core components Celsr2 and Celsr3 shows that they control the differentiation of endocrine cells from polarized progenitors, with a prevalent effect on insulin-producing beta cells. This results in a decreased...

  14. Extrinsic and intrinsic factors controlling spermatogonial stem cell self-renewal and differentiation

    Directory of Open Access Journals (Sweden)

    Xing-Xing Mei

    2015-06-01

    Full Text Available Spermatogonial stem cells (SSCs, the stem cells responsible for male fertility, are one of a small number of cells with the abilities of both self-renewal and generation of large numbers of haploid cells. Technology improvements, most importantly, transplantation assays and in vitro culture systems have greatly expanded our understanding of SSC self-renewal and differentiation. Many important molecules crucial for the balance between self-renewal and differentiation have been recently identified although the exact mechanism(s remain largely undefined. In this review, we give a brief introduction to SSCs, and then focus on extrinsic and intrinsic factors controlling SSCs self-renewal and differentiation.

  15. Extrinsic and intrinsic factors controlling spermatogonial stem cell self-renewal and differentiation.

    Science.gov (United States)

    Mei, Xing-Xing; Wang, Jian; Wu, Ji

    2015-01-01

    Spermatogonial stem cells (SSCs), the stem cells responsible for male fertility, are one of a small number of cells with the abilities of both self-renewal and generation of large numbers of haploid cells. Technology improvements, most importantly, transplantation assays and in vitro culture systems have greatly expanded our understanding of SSC self-renewal and differentiation. Many important molecules crucial for the balance between self-renewal and differentiation have been recently identified although the exact mechanism(s) remain largely undefined. In this review, we give a brief introduction to SSCs, and then focus on extrinsic and intrinsic factors controlling SSCs self-renewal and differentiation.

  16. Oxygen-controlled automated neural differentiation of mouse embryonic stem cells.

    Science.gov (United States)

    Mondragon-Teran, Paul; Tostoes, Rui; Mason, Chris; Lye, Gary J; Veraitch, Farlan S

    2013-03-01

    Automation and oxygen tension control are two tools that provide significant improvements to the reproducibility and efficiency of stem cell production processes. the aim of this study was to establish a novel automation platform capable of controlling oxygen tension during both the cell-culture and liquid-handling steps of neural differentiation processes. We built a bespoke automation platform, which enclosed a liquid-handling platform in a sterile, oxygen-controlled environment. An airtight connection was used to transfer cell culture plates to and from an automated oxygen-controlled incubator. Our results demonstrate that our system yielded comparable cell numbers, viabilities, metabolism profiles and differentiation efficiencies when compared with traditional manual processes. Interestingly, eliminating exposure to ambient conditions during the liquid-handling stage resulted in significant improvements in the yield of MAP2-positive neural cells, indicating that this level of control can improve differentiation processes. This article describes, for the first time, an automation platform capable of maintaining oxygen tension control during both the cell-culture and liquid-handling stages of a 2D embryonic stem cell differentiation process.

  17. BRIEF INTRODUCTION TO THEORETICAL INTENTION OF "NEEDLING METHOD FOR TRANQUILLIZATION AND CALMING THE MIND" FOR TREATMENT OF INSOMNIA

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    A set of scientific theories and an effective acupuncture therapy for insomnia about "the needling method for tranquillization and calming the mind" are gradually formed through many years' theoretical and clinical studies. In this paper, the theoretical intention about "the needling method for tranquillization and calming the mind" for treatment of insomnia are briefly introduced mainly from the cause of disease,pathogenesis, therapeutic method and characteristics of composition of a prescription, etc. in order to provide a new train of thoughts and a new method for working out scientific and standard prescriptions in the treatment of insomnia.

  18. Concept for a Differential Lock and Traction Control Model in Automobiles

    Science.gov (United States)

    Shukul, A. K.; Hansra, S. K.

    2014-01-01

    The automobile is a complex integration of electronics and mechanical components. One of the major components is the differential which is limited due to its shortcomings. The paper proposes a concept of a cost effective differential lock and traction for passenger cars to sports utility vehicles alike, employing a parallel braking mechanism coming into action based on the relative speeds of the wheels driven by the differential. The paper highlights the employment of minimum number of components unlike the already existing systems. The system was designed numerically for the traction control and differential lock for the world's cheapest car. The paper manages to come up with all the system parameters and component costing making it a cost effective system.

  19. A fuzzy logic sliding mode controlled electronic differential for a direct wheel drive EV

    Science.gov (United States)

    Ozkop, Emre; Altas, Ismail H.; Okumus, H. Ibrahim; Sharaf, Adel M.

    2015-11-01

    In this study, a direct wheel drive electric vehicle based on an electronic differential system with a fuzzy logic sliding mode controller (FLSMC) is studied. The conventional sliding surface is modified using a fuzzy rule base to obtain fuzzy dynamic sliding surfaces by changing its slopes using the global error and its derivative in a fuzzy logic inference system. The controller is compared with proportional-integral-derivative (PID) and sliding mode controllers (SMCs), which are usually preferred to be used in industry. The proposed controller provides robustness and flexibility to direct wheel drive electric vehicles. The fuzzy logic sliding mode controller, electronic differential system and the overall electrical vehicle mechanism are modelled and digitally simulated by using the Matlab software. Simulation results show that the system with FLSMC has better efficiency and performance compared to those of PID and SMCs.

  20. Differential Evolution-Based PID Control of Nonlinear Full-Car Electrohydraulic Suspensions

    Directory of Open Access Journals (Sweden)

    Jimoh O. Pedro

    2013-01-01

    Full Text Available This paper presents a differential-evolution- (DE- optimized, independent multiloop proportional-integral-derivative (PID controller design for full-car nonlinear, electrohydraulic suspension systems. The multiloop PID control stabilises the actuator via force feedback and also improves the system performance. Controller gains are computed using manual tuning and through DE optimization to minimise a performance index, which addresses suspension travel, road holding, vehicle handling, ride comfort, and power consumption constraints. Simulation results showed superior performance of the DE-optimized PID-controlled active vehicle suspension system (AVSS over the manually tuned PID-controlled AVSS and the passive vehicle suspension system (PVSS.

  1. Aubergine Controls Germline Stem Cell Self-Renewal and Progeny Differentiation via Distinct Mechanisms.

    Science.gov (United States)

    Ma, Xing; Zhu, Xiujuan; Han, Yingying; Story, Benjamin; Do, Trieu; Song, Xiaoqing; Wang, Su; Zhang, Ying; Blanchette, Marco; Gogol, Madelaine; Hall, Kate; Peak, Allison; Anoja, Perera; Xie, Ting

    2017-04-24

    Piwi family protein Aubergine (Aub) maintains genome integrity in late germ cells of the Drosophila ovary through Piwi-associated RNA-mediated repression of transposon activities. Although it is highly expressed in germline stem cells (GSCs) and early progeny, it remains unclear whether it plays any roles in early GSC lineage development. Here we report that Aub promotes GSC self-renewal and GSC progeny differentiation. RNA-iCLIP results show that Aub binds the mRNAs encoding self-renewal and differentiation factors in cultured GSCs. Aub controls GSC self-renewal by preventing DNA-damage-induced Chk2 activation and by translationally controlling the expression of self-renewal factors. It promotes GSC progeny differentiation by translationally controlling the expression of differentiation factors, including Bam. Therefore, this study reveals a function of Aub in GSCs and their progeny, which promotes translation of self-renewal and differentiation factors by directly binding to its target mRNAs and interacting with translational initiation factors. Copyright © 2017 Elsevier Inc. All rights reserved.

  2. Experimental typing of the entry efficiency in calm air of an annular slot sampler; Determination experimentale de l'efficacite de captage en air calme d'un echantillonneur a fente annulaire

    Energy Technology Data Exchange (ETDEWEB)

    Roger, F.; Fabries, J.F.; Gorner, P.; Wrobel, R. [Institut National de Recherche et de Securite, INRS, Lab. de Metrologie de la Pollution par les Aerosols, 54 - Vandoeuvre-Les-Nancy (France); Renoux, A. [Paris-12 Univ., Lab. de Physique des Aerosols et de Transfert des Contaminations, 94 - Creteil (France)

    2000-07-01

    Aerosol sampling is a complex physical process that depends on many parameters like particle size, wind speed, aspiration velocity and sampler geometry. Inertia has a predominant influence on particle motion in moving air for particle size above 1 {mu}m. In calm air where air movement is mainly induced by the aspiration orifice of the sampler, gravitational settling affects more deeply particle motion and hence sampler performance. The entry efficiency of a sampler with an annular aspiration slot was recently measured for several conditions of aspiration flow rate, wind speed (1 and 3 m s{sup -1}) and geometric parameters of the sampler as a function of particle aerodynamic diameter. Some complementary work was carried out to add new experimental data corresponding to the same sampler in calm air. The results were obtained for 9 configurations, combining several values of disc diameter, aspiration slot width, and aspiration velocity. A semi-empirical model was developed from the data that enables the calculation of particle entry efficiency of the annular sampler in calm air. In addition, a numerical study was carried out to calculate the particle trajectories approaching the annular aspiration slot of the sampler. The results show that particle rebounds on the sampler walls have a significant effect on the entry efficiency of the sampler in calm air. (authors)

  3. On the Controllability of a Differential Equation with Delayed and Advanced Arguments

    Directory of Open Access Journals (Sweden)

    Raúl Manzanilla

    2010-01-01

    Full Text Available A semigroup theory for a differential equation with delayed and advanced arguments is developed, with a detailed description of the infinitesimal generator. This in turn allows to study the exact controllability of the equation, by rewriting it as a classical Cauchy problem.

  4. Application of partial differential equation modeling of the control/structural dynamics of flexible spacecraft

    Science.gov (United States)

    Taylor, Lawrence W., Jr.; Rajiyah, H.

    1991-01-01

    Partial differential equations for modeling the structural dynamics and control systems of flexible spacecraft are applied here in order to facilitate systems analysis and optimization of these spacecraft. Example applications are given, including the structural dynamics of SCOLE, the Solar Array Flight Experiment, the Mini-MAST truss, and the LACE satellite. The development of related software is briefly addressed.

  5. Race, Family Structure, and Delinquency: A Test of Differential Association and Social Control Theories.

    Science.gov (United States)

    Matsueda, Ross L.; Heimer, Karen

    1987-01-01

    Broken homes have a larger impact on delinquency among Blacks than non-Blacks. In both populations, the effects of broken homes and attachment to parents and peers are mediated by the learning of definitions of delinquency, a finding that supports differential association over social control theory. (Author/BJV)

  6. Use of a Differential Observing Response to Expand Restricted Stimulus Control

    Science.gov (United States)

    Walpole, Carrie Wallace; Roscoe, Eileen M.; Dube, William V.

    2007-01-01

    This study extends previous work on the use of differential observing responses (DOR) to remediate atypically restricted stimulus control. A participant with autism had high matching-to-sample accuracy scores with printed words that had no letters in common (e.g., "cat," "lid," "bug") but poor accuracy with words that had two letters in common…

  7. Ultraprecise parabolic interpolator for numerically controlled machine tools. [Digital differential analyzer circuit

    Energy Technology Data Exchange (ETDEWEB)

    Davenport, C. M.

    1977-02-01

    The mathematical basis for an ultraprecise digital differential analyzer circuit for use as a parabolic interpolator on numerically controlled machines has been established, and scaling and other error-reduction techniques have been developed. An exact computer model is included, along with typical results showing tracking to within an accuracy of one part per million.

  8. External rostral characters for differentiation of sexes in the biological control agent Mecinus janthinus (Coleoptera: Curculionidae)

    Science.gov (United States)

    Marjolein Schat; Sharlene E. Sing; Robert K. D. Peterson

    2007-01-01

    The stem-boring weevil, Mecinus janthinus (Germar), is a promising, well established classical biological control agent for the exotic invasive weed Dalmatian toadflax (Linaria dalmatica (L.) Mill.) (Scrophulariaceae). In this paper we present readily apparent rostral characters that can be used for sex differentiation of live stem-boring weevils at low magnification....

  9. An approximation theory for nonlinear partial differential equations with applications to identification and control

    Science.gov (United States)

    Banks, H. T.; Kunisch, K.

    1982-01-01

    Approximation results from linear semigroup theory are used to develop a general framework for convergence of approximation schemes in parameter estimation and optimal control problems for nonlinear partial differential equations. These ideas are used to establish theoretical convergence results for parameter identification using modal (eigenfunction) approximation techniques. Results from numerical investigations of these schemes for both hyperbolic and parabolic systems are given.

  10. Area-specific temporal control of corticospinal motor neuron differentiation by COUP-TFI

    Science.gov (United States)

    Tomassy, Giulio Srubek; De Leonibus, Elvira; Jabaudon, Denis; Lodato, Simona; Alfano, Christian; Mele, Andrea; Macklis, Jeffrey D.; Studer, Michèle

    2010-01-01

    Transcription factors with gradients of expression in neocortical progenitors give rise to distinct motor and sensory cortical areas by controlling the area-specific differentiation of distinct neuronal subtypes. However, the molecular mechanisms underlying this area-restricted control are still unclear. Here, we show that COUP-TFI controls the timing of birth and specification of corticospinal motor neurons (CSMN) in somatosensory cortex via repression of a CSMN differentiation program. Loss of COUP-TFI function causes an area-specific premature generation of neurons with cardinal features of CSMN, which project to subcerebral structures, including the spinal cord. Concurrently, genuine CSMN differentiate imprecisely and do not project beyond the pons, together resulting in impaired skilled motor function in adult mice with cortical COUP-TFI loss-of-function. Our findings indicate that COUP-TFI exerts critical areal and temporal control over the precise differentiation of CSMN during corticogenesis, thereby enabling the area-specific functional features of motor and sensory areas to arise. PMID:20133588

  11. Controllability of impulsive neutral functional differential inclusions with infinite delay in Banach spaces

    Energy Technology Data Exchange (ETDEWEB)

    Chang, Y.-K. [Department of Mathematics, Lanzhou Jiaotong University, Lanzhou, Gansu 730070 (China)], E-mail: lzchangyk@163.com; Anguraj, A. [Department of Mathematics, PSG College of Arts and Science, Coimbatore 641 014, Tamil Nadu (India)], E-mail: angurajpsg@yahoo.com; Mallika Arjunan, M. [Department of Mathematics, PSG College of Arts and Science, Coimbatore 641 014, Tamil Nadu (India)], E-mail: arjunphd07@yahoo.co.in

    2009-02-28

    In this work, we establish a sufficient condition for the controllability of the first-order impulsive neutral functional differential inclusions with infinite delay in Banach spaces. The results are obtained by using the Dhage's fixed point theorem.

  12. miRNA-720 controls stem cell phenotype, proliferation and differentiation of human dental pulp cells.

    Directory of Open Access Journals (Sweden)

    Emilio Satoshi Hara

    Full Text Available Dental pulp cells (DPCs are known to be enriched in stem/progenitor cells but not well characterized yet. Small non-coding microRNAs (miRNAs have been identified to control protein translation, mRNA stability and transcription, and have been reported to play important roles in stem cell biology, related to cell reprogramming, maintenance of stemness and regulation of cell differentiation. In order to characterize dental pulp stem/progenitor cells and its mechanism of differentiation, we herein sorted stem-cell-enriched side population (SP cells from human DPCs and periodontal ligament cells (PDLCs, and performed a locked nucleic acid (LNA-based miRNA array. As a result, miR-720 was highly expressed in the differentiated main population (MP cells compared to that in SP cells. In silico analysis and a reporter assay showed that miR-720 targets the stem cell marker NANOG, indicating that miR-720 could promote differentiation of dental pulp stem/progenitor cells by repressing NANOG. Indeed, gain-and loss-of-function analyses showed that miR-720 controls NANOG transcript and protein levels. Moreover, transfection of miR-720 significantly decreased the number of cells positive for the early stem cell marker SSEA-4. Concomitantly, mRNA levels of DNA methyltransferases (DNMTs, which are known to play crucial factors during stem cell differentiation, were also increased by miR-720 through unknown mechanism. Finally, miR-720 decreased DPC proliferation as determined by immunocytochemical analysis against ki-67, and promoted odontogenic differentiation as demonstrated by alizarin red staining, as well as alkaline phosphatase and osteopontin mRNA levels. Our findings identify miR-720 as a novel miRNA regulating the differentiation of DPCs.

  13. Approximate controllability of Sobolev type fractional stochastic nonlocal nonlinear differential equations in Hilbert spaces

    Directory of Open Access Journals (Sweden)

    Mourad Kerboua

    2014-12-01

    Full Text Available We introduce a new notion called fractional stochastic nonlocal condition, and then we study approximate controllability of class of fractional stochastic nonlinear differential equations of Sobolev type in Hilbert spaces. We use Hölder's inequality, fixed point technique, fractional calculus, stochastic analysis and methods adopted directly from deterministic control problems for the main results. A new set of sufficient conditions is formulated and proved for the fractional stochastic control system to be approximately controllable. An example is given to illustrate the abstract results.

  14. Composition and source apportionment of fine particulate matter during extended calm periods in the city of Rijeka, Croatia

    Science.gov (United States)

    Ivošević, T.; Orlić, I.; Bogdanović Radović, I.; Čargonja, M.; Stelcer, E.

    2017-09-01

    In the city of Rijeka, Croatia, an extended, two-year aerosol pollution monitoring campaign was recently completed. During that period, 345 samples of fine fraction of aerosols were collected on stretched Teflon filters. All samples were analyzed by Ion Beam Analysis techniques Proton Induced X-ray Emission and Proton Induced γ-Ray Emission and concentrations of 22 elements were determined. Concentrations of black carbon were determined by Laser Integrated Plate Method. For the Bay of Kvarner, where the city of Rijeka is located, long periods of calm weather are common. As a consequence, during these periods, air pollution is steadily increasing. To pin-point and characterize local, mostly anthropogenic, air pollution sources, only samples collected during the extended calm periods were used in this work. As a cut-off wind speed, speed of 1.5 m/s was used. In that way, out of all 345 samples, only 188 were selected. Those samples were statistically evaluated by means of positive matrix factorization. Results show that from all anthropogenic sources (vehicles, secondary sulphates, smoke, heavy oil combustion, road dust, industry Fe and port activities) only secondary sulphates and heavy oil combustion were significantly higher (40% and 50%, respectively) during calm periods. On the other hand, natural components of aerosol pollution such as soil and sea salts, (typically present in concentrations of 1.4% and 9%, respectively) are practically non-existent for calm weather conditions.

  15. Correction: Keep Calm and Learn Multilevel Logistic Modeling: A Simplified Three-Step Procedure Using Stata, R, Mplus, and SPSS

    Directory of Open Access Journals (Sweden)

    Nicolas Sommet

    2017-12-01

    Full Text Available This article details a correction to the article: Sommet, N. & Morselli, D., (2017. Keep Calm and Learn Multilevel Logistic Modeling: A Simplified Three-Step Procedure Using Stata, R, Mplus, and SPSS. 'International Review of Social Psychology'. 30(1, pp. 203–218. DOI: https://doi.org/10.5334/irsp.90

  16. Rac2 controls tumor growth, metastasis and M1-M2 macrophage differentiation in vivo.

    Directory of Open Access Journals (Sweden)

    Shweta Joshi

    Full Text Available Although it is well-established that the macrophage M1 to M2 transition plays a role in tumor progression, the molecular basis for this process remains incompletely understood. Herein, we demonstrate that the small GTPase, Rac2 controls macrophage M1 to M2 differentiation and the metastatic phenotype in vivo. Using a genetic approach, combined with syngeneic and orthotopic tumor models we demonstrate that Rac2-/- mice display a marked defect in tumor growth, angiogenesis and metastasis. Microarray, RT-PCR and metabolomic analysis on bone marrow derived macrophages isolated from the Rac2-/- mice identify an important role for Rac2 in M2 macrophage differentiation. Furthermore, we define a novel molecular mechanism by which signals transmitted from the extracellular matrix via the α4β1 integrin and MCSF receptor lead to the activation of Rac2 and potentially regulate macrophage M2 differentiation. Collectively, our findings demonstrate a macrophage autonomous process by which the Rac2 GTPase is activated downstream of the α4β1 integrin and the MCSF receptor to control tumor growth, metastasis and macrophage differentiation into the M2 phenotype. Finally, using gene expression and metabolomic data from our Rac2-/- model, and information related to M1-M2 macrophage differentiation curated from the literature we executed a systems biologic analysis of hierarchical protein-protein interaction networks in an effort to develop an iterative interactome map which will predict additional mechanisms by which Rac2 may coordinately control macrophage M1 to M2 differentiation and metastasis.

  17. Chaos Enhanced Differential Evolution in the Task of Evolutionary Control of Discrete Chaotic LOZI Map

    Directory of Open Access Journals (Sweden)

    Roman Senkerik

    2016-01-01

    Full Text Available In this paper, evolutionary technique Differential Evolution (DE is used for the evolutionary tuning of controller parameters for the stabilization of selected discrete chaotic system, which is the two-dimensional Lozi map. The novelty of the approach is that the selected controlled discrete dissipative chaotic system is used within Chaos enhanced heuristic concept as the chaotic pseudo-random number generator to drive the mutation and crossover process in the DE. The idea was to utilize the hidden chaotic dynamics in pseudo-random sequences given by chaotic map to help Differential evolution algorithm in searching for the best controller settings for the same chaotic system. The optimizations were performed for three different required final behavior of the chaotic system, and two types of developed cost function. To confirm the robustness of presented approach, comparisons with canonical DE strategy and PSO algorithm have been performed.

  18. A metabolic switch controls intestinal differentiation downstream of Adenomatous polyposis coli (APC).

    Science.gov (United States)

    Sandoval, Imelda T; Delacruz, Richard Glenn C; Miller, Braden N; Hill, Shauna; Olson, Kristofor A; Gabriel, Ana E; Boyd, Kevin; Satterfield, Christeena; Remmen, Holly Van; Rutter, Jared; Jones, David A

    2017-04-11

    Elucidating signaling pathways that regulate cellular metabolism is essential for a better understanding of normal development and tumorigenesis. Recent studies have shown that mitochondrial pyruvate carrier 1 (MPC1) , a crucial player in pyruvate metabolism, is downregulated in colon adenocarcinomas. Utilizing zebrafish to examine the genetic relationship between MPC1 and Adenomatous polyposis coli (APC), a key tumor suppressor in colorectal cancer, we found that apc controls the levels of mpc1 and that knock down of mpc1 recapitulates phenotypes of impaired apc function including failed intestinal differentiation. Exogenous human MPC1 RNA rescued failed intestinal differentiation in zebrafish models of apc deficiency. Our data demonstrate a novel role for apc in pyruvate metabolism and that pyruvate metabolism dictates intestinal cell fate and differentiation decisions downstream of apc .

  19. Proton NMR metabolic profiling of CSF reveals distinct differentiation of meningitis from negative controls.

    Science.gov (United States)

    Chatterji, Tanushri; Singh, Suruchi; Sen, Manodeep; Singh, Ajai Kumar; Agarwal, Gaurav Raj; Singh, Deepak Kumar; Srivastava, Janmejai Kumar; Singh, Alka; Srivastava, Rajeshwar Nath; Roy, Raja

    2017-06-01

    Cerebrospinal fluid (CSF) is an essential bio-fluid of the central nervous system (CNS), playing a vital role in the protection of CNS and performing neuronal function regulation. The chemical composition of CSF varies during onset of meningitis, neurodegenerative disorders (positive controls) and in traumatic cases (negative controls). The study design was broadly categorized into meningitis cases, negative controls and positive controls. Further differentiation among the three groups was carried out using Principal Component Analysis (PCA) followed by supervised Partial Least Square Discriminant Analysis (PLS-DA). The statistical analysis of meningitis vs. negative controls using PLS-DA model resulted in R 2 of 0.97 and Q 2 of 0.85. There was elevation in the levels of ketone bodies, total free amino acids, glutamine, creatine, citrate and choline containing compounds (choline and GPC) in meningitis cases. Similarly, meningitis vs. positive controls resulted in R 2 of 0.80 and Q 2 of 0.60 and showed elevation in the levels of total free amino acids, glutamine, creatine/creatinine and citrate in the meningitis group. Four cases of HIV were identified by PLS-DA model as well as by clinical investigations. On the basis of metabolic profile it was found that negative control CSF samples are more appropriate for differentiation of meningitis than positive control CSF samples. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. Novel lncRNAs in myogenesis: a miR-31 overlapping transcript controls myoblast differentiation.

    KAUST Repository

    Ballarino, Monica; Cazzella, Valentina; D'Andrea, Daniel; Grassi, Luigi; Bisceglie, Lavinia; Cipriano, Andrea; Santini, Tiziana; Pinnarò , Chiara; Morlando, Mariangela; Tramontano, Anna; Bozzoni, Irene

    2014-01-01

    Transcriptome analysis allowed the identification of new long noncoding RNAs differentially expressed during murine myoblast differentiation. These transcripts were classified on the basis of their expression under proliferating versus differentiated conditions, muscle-restricted activation, and subcellular localization. Several species displayed preferential expression in dystrophic (mdx) versus wild-type muscles, indicating their possible link with regenerative processes. One of the identified transcripts, lnc-31, even if originating from the same nuclear precursor of miR-31, is produced by a pathway mutually exclusive. We show that lnc-31 and its human homologue hsa-lnc-31 are expressed in proliferating myoblasts, where they counteract differentiation. In line with this, both species are more abundant in mdx muscles and in human Duchenne muscular dystrophy (DMD) myoblasts, than in their normal counterparts. Altogether, these data suggest a crucial role for lnc-31 in controlling the differentiation commitment of precursor myoblasts and indicate that its function is maintained in evolution despite the poor sequence conservation with the human counterpart.

  1. Novel lncRNAs in myogenesis: a miR-31 overlapping transcript controls myoblast differentiation.

    KAUST Repository

    Ballarino, Monica

    2014-12-15

    Transcriptome analysis allowed the identification of new long noncoding RNAs differentially expressed during murine myoblast differentiation. These transcripts were classified on the basis of their expression under proliferating versus differentiated conditions, muscle-restricted activation, and subcellular localization. Several species displayed preferential expression in dystrophic (mdx) versus wild-type muscles, indicating their possible link with regenerative processes. One of the identified transcripts, lnc-31, even if originating from the same nuclear precursor of miR-31, is produced by a pathway mutually exclusive. We show that lnc-31 and its human homologue hsa-lnc-31 are expressed in proliferating myoblasts, where they counteract differentiation. In line with this, both species are more abundant in mdx muscles and in human Duchenne muscular dystrophy (DMD) myoblasts, than in their normal counterparts. Altogether, these data suggest a crucial role for lnc-31 in controlling the differentiation commitment of precursor myoblasts and indicate that its function is maintained in evolution despite the poor sequence conservation with the human counterpart.

  2. A new module in neural differentiation control: two microRNAs upregulated by retinoic acid, miR-9 and -103, target the differentiation inhibitor ID2.

    Directory of Open Access Journals (Sweden)

    Daniela Annibali

    Full Text Available The transcription factor ID2 is an important repressor of neural differentiation strongly implicated in nervous system cancers. MicroRNAs (miRNAs are increasingly involved in differentiation control and cancer development. Here we show that two miRNAs upregulated on differentiation of neuroblastoma cells--miR-9 and miR-103--restrain ID2 expression by directly targeting the coding sequence and 3' untranslated region of the ID2 encoding messenger RNA, respectively. Notably, the two miRNAs show an inverse correlation with ID2 during neuroblastoma cell differentiation induced by retinoic acid. Overexpression of miR-9 and miR-103 in neuroblastoma cells reduces proliferation and promotes differentiation, as it was shown to occur upon ID2 inhibition. Conversely, an ID2 mutant that cannot be targeted by either miRNA prevents retinoic acid-induced differentiation more efficient than wild-type ID2. These findings reveal a new regulatory module involving two microRNAs upregulated during neural differentiation that directly target expression of the key differentiation inhibitor ID2, suggesting that its alteration may be involved in neural cancer development.

  3. Greenhouse gas emission controls : differentiated vs. flat rate targets : impacts and concerts

    International Nuclear Information System (INIS)

    Heydanek, D.

    1997-01-01

    Continuing the discussion on differentiation in greenhouse gas emission targets and timetables for all nations, the different implications of differentiation vs. flat rate controls were examined. A scenario of how different targets for different countries based on national circumstances might be implemented, was presented. Implications of differentiation for the Dow Chemical Company were also reviewed. For more than 20 years, Dow has practiced leading edge energy efficiency in environmental management systems and has committed to a series of environmental, health and safety goals. The company believes that at the international level, fully differentiated targets and timetables need to be negotiated, party by party, by the 150 nations who agreed to stabilize greenhouse gas emissions at 1990 levels by year 2000. It was suggested that a strong disincentive exists to delivering energy efficiency beyond compliance. It was predicted that despite efficiency, the energy intensive assets in place today in Annex I countries will be disadvantaged and prematurely retired as the costs of greenhouse gas emission controls grow and exert pressure to move productive capacity offshore

  4. Small functional groups for controlled differentiation of hydrogel-encapsulated human mesenchymal stem cells

    Science.gov (United States)

    Benoit, Danielle S. W.; Schwartz, Michael P.; Durney, Andrew R.; Anseth, Kristi S.

    2008-10-01

    Cell-matrix interactions have critical roles in regeneration, development and disease. The work presented here demonstrates that encapsulated human mesenchymal stem cells (hMSCs) can be induced to differentiate down osteogenic and adipogenic pathways by controlling their three-dimensional environment using tethered small-molecule chemical functional groups. Hydrogels were formed using sufficiently low concentrations of tether molecules to maintain constant physical characteristics, encapsulation of hMSCs in three dimensions prevented changes in cell morphology, and hMSCs were shown to differentiate in normal growth media, indicating that the small-molecule functional groups induced differentiation. To our knowledge, this is the first example where synthetic matrices are shown to control induction of multiple hMSC lineages purely through interactions with small-molecule chemical functional groups tethered to the hydrogel material. Strategies using simple chemistry to control complex biological processes would be particularly powerful as they could make production of therapeutic materials simpler, cheaper and more easily controlled.

  5. Regionally differentiated air pollution control regulations in the installation-related emission control law of the Federal Republic of Germany

    International Nuclear Information System (INIS)

    Buettner, T.W.

    1992-01-01

    The volume treats an issue from the boundary zone between environmental law and environmental economics, namely the regionalization of air pollution control standards in installation-related emission control law. In order to examine the question of whether this proposal, which originates in the field of environmental economics, can be adopted and is purposeful, the author initially performs a complete inventorization of applicable norms, this covering emission control law, the law of regional planning, and the provisions of international law. This status quo is then reviewed using conformity and optimization criteria developed by the political sciences. The assessment comes to the conclusion that the introduction of regionally differentiated air pollution control standards is not desirable. The author further submits proposals for the streamlining of the law of installation-related air pollution control in the Federal Republic of Germany. (orig.) [de

  6. Energetically efficient proportional-integral-differential (PID) control of wake vortices behind a circular cylinder

    International Nuclear Information System (INIS)

    Das, Pramode K; Mathew, Sam; Shaiju, A J; Patnaik, B S V

    2016-01-01

    The control of vortex shedding behind a circular cylinder is a precursor to a wide range of external shear flow problems in engineering, in particular the flow-induced vibrations. In the present study, numerical simulation of an energetically efficient active flow control strategy is proposed, for the control of wake vortices behind a circular cylinder at a low Reynolds number of 100. The fluid is assumed to be incompressible and Newtonian with negligible variation in properties. Reflectionally symmetric controllers are designed such that, they are located on a small sector of the cylinder over which, tangential sliding mode control is imparted. In the field of modern controls, proportional (P), integral (I) and differential (D) control strategies and their numerous combinations are extremely popular in industrial practice. To impart suitable control actuation, the vertically varying lift force on the circular cylinder, is synthesised for the construction of an error term. Four different types of controllers considered in the present study are, P, I, PI and PID. These controllers are evaluated for their energetic efficiency and performance. A linear quadratic optimal control problem is formulated, to minimise the cost functional. By performing detailed simulations, it was observed that, the system is energetically efficient, even when the twin eddies are still persisting behind the circular cylinder. To assess the adaptability of the controllers, the actuators were switched on and off to study their dynamic response. (paper)

  7. Indian Hedgehog Controls Proliferation and Differentiation in Skin Tumorigenesis and Protects against Malignant Progression

    Directory of Open Access Journals (Sweden)

    Parisa Kakanj

    2013-07-01

    Full Text Available Mutations in the hedgehog pathway drive the formation of tumors in many different organs, including the development of basal cell carcinoma in the skin. However, little is known about the role of epidermal Indian hedgehog (Ihh in skin physiology. Using mouse genetics, we identified overlapping and distinct functions of Ihh in different models of epidermal tumorigenesis. Epidermal deletion of Ihh resulted in increased formation of benign squamous papilloma. Strikingly, Ihh-deficient mice showed an increase in malignant squamous cell carcinoma and developed lung and lymph node metastases. In a sebaceous gland tumor model, Ihh deficiency inhibited tumor cell differentiation. More mechanistically, IHH stimulated cell proliferation by activating the transcription factor GLI2 in human keratinocytes and human tumors. Thus, our results uncover important functions for Ihh signaling in controlling proliferation, differentiation, malignant progression, and metastasis of epithelial cancer, establishing Ihh as a gatekeeper for controlling the grade of tumor malignancy.

  8. Novel Numerical Methods for Optimal Control Problems Involving Fractional-Order Differential Equations

    Science.gov (United States)

    2018-03-14

    UNIVERSITY OF TECHNOLOGY Final Report 03/14/2018 DISTRIBUTION A: Distribution approved for public release. AF Office Of Scientific Research (AFOSR...optimal control problems involving fractional-order differential equations Wang, Song Curtin University of Technology Kent Street, Bentley WA6102...Article history : Received 3 October 2016 Accepted 26 March 2017 Available online 29 April 2017 Keywords: Hamilton–Jacobi–Bellman equation Financial

  9. Legendre-tau approximation for functional differential equations. II - The linear quadratic optimal control problem

    Science.gov (United States)

    Ito, Kazufumi; Teglas, Russell

    1987-01-01

    The numerical scheme based on the Legendre-tau approximation is proposed to approximate the feedback solution to the linear quadratic optimal control problem for hereditary differential systems. The convergence property is established using Trotter ideas. The method yields very good approximations at low orders and provides an approximation technique for computing closed-loop eigenvalues of the feedback system. A comparison with existing methods (based on averaging and spline approximations) is made.

  10. Legendre-tau approximation for functional differential equations. Part 2: The linear quadratic optimal control problem

    Science.gov (United States)

    Ito, K.; Teglas, R.

    1984-01-01

    The numerical scheme based on the Legendre-tau approximation is proposed to approximate the feedback solution to the linear quadratic optimal control problem for hereditary differential systems. The convergence property is established using Trotter ideas. The method yields very good approximations at low orders and provides an approximation technique for computing closed-loop eigenvalues of the feedback system. A comparison with existing methods (based on averaging and spline approximations) is made.

  11. Novel Differential Current Control Strategy Based on a Modified Three-Level SVPWM for Two Parallel-Connected Inverters

    DEFF Research Database (Denmark)

    Zorig, Abdelmalik; Barkat, Said; Belkheiri, Mohammed

    2017-01-01

    Recently, parallel inverters have been investigated to provide multilevel characteristics besides their advantage to increase the power system capacity, reliability, and efficiency. However, the issue of differential currents imbalance remains a challenge in parallel inverter operation. The distr......Recently, parallel inverters have been investigated to provide multilevel characteristics besides their advantage to increase the power system capacity, reliability, and efficiency. However, the issue of differential currents imbalance remains a challenge in parallel inverter operation....... The distribution of switching vectors of the resulting multilevel topology has a certain degree of self-differential current balancing properties. Nevertheless, the method alone is not sufficient to maintain balanced differential current in practical applications. This paper proposes a closed-loop differential...... current control method by introducing a control variable adjusting the dwell time of the selected switching vectors and thus maintaining the differential currents balanced without affecting the overall system performance. The control strategy, including distribution of switching sequence, selection...

  12. Control of Adipocyte Differentiation in Different Fat Depots; Implications for Pathophysiology or Therapy

    Directory of Open Access Journals (Sweden)

    Xiuquan eMa

    2015-01-01

    Full Text Available Adipocyte differentiation and its impact on restriction or expansion of particular adipose tissue depots has physiological and pathophysiological significance in view of the different functions of these depots. Brown or beige fat [BAT] expansion can enhance thermogenesis, lipid oxidation, insulin sensitivity and glucose tolerance; conversely expanded visceral fat [VAT] is associated with insulin resistance, low grade inflammation, dyslipidaemia and cardiometabolic risk. The largest depot, subcutaneous white fat [WAT], has important beneficial characteristics including storage of lipid out of harms way and secretion of adipokines, especially leptin and adiponectin, with positive metabolic effects including lipid oxidation, energy utilisation, enhanced insulin action and an anti-inflammatory role. The absence of these functions in lipodystrophies leads to major metabolic disturbances. An ability to expand WAT adipocyte differentiation would seem an important defence mechanism against the detrimental effects of energy excess and limit harmful accumulation of lipid in ectopic sites, such as liver and muscle.Adipocyte differentiation involves a transcriptional cascade with PPARg being most important in WAT but less so in VAT, with increased angiogenesis also critical. The transcription factor, Islet1, is fairly specific to VAT and in vitro inhibits adipocyte differentiation. The physiological importance of Islet1 requires further study. Basic control of differentiation is similar in BAT but important differences include the effect of PGC-1a on mitochondrial biosynthesis and upregulation of UCP1; also PRDM16 plays a pivotal role in expression of the BAT phenotype.Modulation of the capacity or function of these different adipose tissue depots, by altering adipocyte differentiation or other means, holds promise for interventions that can be helpful in human disease, particularly cardiometabolic disorders associated with the world wide explosion of

  13. Language experience differentiates prefrontal and subcortical activation of the cognitive control network in novel word learning.

    Science.gov (United States)

    Bradley, Kailyn A L; King, Kelly E; Hernandez, Arturo E

    2013-02-15

    The purpose of this study was to examine the cognitive control mechanisms in adult English speaking monolinguals compared to early sequential Spanish-English bilinguals during the initial stages of novel word learning. Functional magnetic resonance imaging during a lexico-semantic task after only 2h of exposure to novel German vocabulary flashcards showed that monolinguals activated a broader set of cortical control regions associated with higher-level cognitive processes, including the supplementary motor area (SMA), anterior cingulate (ACC), and dorsolateral prefrontal cortex (DLPFC), as well as the caudate, implicated in cognitive control of language. However, bilinguals recruited a more localized subcortical network that included the putamen, associated more with motor control of language. These results suggest that experience managing multiple languages may differentiate the learning strategy and subsequent neural mechanisms of cognitive control used by bilinguals compared to monolinguals in the early stages of novel word learning. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Nonlinear model predictive control of a wave energy converter based on differential flatness parameterisation

    Science.gov (United States)

    Li, Guang

    2017-01-01

    This paper presents a fast constrained optimization approach, which is tailored for nonlinear model predictive control of wave energy converters (WEC). The advantage of this approach relies on its exploitation of the differential flatness of the WEC model. This can reduce the dimension of the resulting nonlinear programming problem (NLP) derived from the continuous constrained optimal control of WEC using pseudospectral method. The alleviation of computational burden using this approach helps to promote an economic implementation of nonlinear model predictive control strategy for WEC control problems. The method is applicable to nonlinear WEC models, nonconvex objective functions and nonlinear constraints, which are commonly encountered in WEC control problems. Numerical simulations demonstrate the efficacy of this approach.

  15. Gibberellin mediates daylength-controlled differentiation of vegetative meristems in strawberry (Fragaria × ananassa Duch

    Directory of Open Access Journals (Sweden)

    Moritz Thomas

    2009-02-01

    Full Text Available Abstract Background Differentiation of long and short shoots is an important developmental trait in several species of the Rosaceae family. However, the physiological mechanisms controlling this differentiation are largely unknown. We have studied the role of gibberellin (GA in regulation of shoot differentiation in strawberry (Fragaria × ananassa Duch. cv. Korona. In strawberry, differentiation of axillary buds to runners (long shoot or to crown branches (short shoot is promoted by long-day and short-day conditions, respectively. Formation of crown branches is a prerequisite for satisfactory flowering because inflorescences are formed from the apical meristems of the crown. Results We found that both prohexadione-calcium and short photoperiod inhibited runner initiation and consequently led to induction of crown branching. In both cases, this correlated with a similar decline in GA1 level. Exogenous GA3 completely reversed the effect of prohexadione-calcium in a long photoperiod, but was only marginally effective in short-day grown plants. However, transfer of GA3-treated plants from short days to long days restored the normal runner formation. This did not occur in plants that were not treated with GA3. We also studied GA signalling homeostasis and found that the expression levels of several GA biosynthetic, signalling and target genes were similarly affected by prohexadione-calcium and short photoperiod in runner tips and axillary buds, respectively. Conclusion GA is needed for runner initiation in strawberry, and the inhibition of GA biosynthesis leads to the formation of crown branches. Our findings of similar changes in GA levels and in GA signalling homeostasis after prohexadione-calcium and short-day treatments, and photoperiod-dependent responsiveness of the axillary buds to GA indicate that GA plays a role also in the photoperiod-regulated differentiation of axillary buds. We propose that tightly regulated GA activity may control

  16. Differentiating non-motor symptoms in Parkinson's disease from controls and hemifacial spasm.

    Directory of Open Access Journals (Sweden)

    Ming-Hui Yong

    Full Text Available BACKGROUND AND AIMS: Non-motor symptoms (NMS are important manifestations of Parkinson's disease (PD that reduce patients' health-related quality of life. Some NMS may also be caused by age-related changes, or manifested as a psychological reaction to a chronic neurological condition. This case-control study compared the NMS burden among PD patients, healthy controls and hemifacial spasm (HFS patients. In addition, we determined the NMS that discriminated between PD and non-PD subjects. METHODS: 425 subjects were recruited from a tertiary hospital in Singapore (200 PD patients, 150 healthy controls and 75 HFS patients. NMS burden in subjects was measured using the Non-Motor Symptoms Scale (NMSS. RESULTS: NMSS total score was significantly higher in PD patients (37.9±2.6 compared to healthy controls (11.2±0.9 (p<0.0001 and HFS patients (18.0±2.1 (p<0.0001. In addition, NMSS total score was significantly higher in HFS patients compared to healthy controls (p = 0.003. PD patients experienced a higher NMS burden than healthy controls in all domains, and a higher NMS burden than HFS patients in all but attention/memory and urinary domains. NMS burden for HFS and healthy controls differed only in the sleep/fatigue and urinary domains. Using stepwise logistic regression, problems of 'constipation', 'restless legs', 'dribbling saliva', 'altered interest in sex' and 'change in taste or smell' were found to have significant discriminative power in differentiating between PD patients and healthy controls and between PD patients and HFS patients. CONCLUSION: PD patients experienced a greater overall NMS burden compared to both healthy controls and HFS patients. HFS patients demonstrated a higher NMS burden than controls, and some NMS may be common to chronic neurological conditions while others are more specific to PD. Differentiating patients using NMS domains may help refine the clinical management of NMS in PD patients.

  17. Radiative warming of the air observed near a bare-soil surface on calm clear nights

    International Nuclear Information System (INIS)

    Sang, N.; Kobayahsi, T.

    1999-01-01

    The radiative flux in the lowest three meters above a bare-soil surface was directly measured on calm nights with little cloud cover. Although divergence of upward radiative flux occurred above 1m, convergence was often observed between 0.2m and 1m all through the night. Almost the same results were obtained for the net flux except that the transitional height between divergence and convergence was some tens of centimeters, which means that radiative warming occurred just above the bare-soil surface during the night. This phenomenon can be explained by postulating that cold air is produced by conduction at the surface of small heat-insulated projections (HIPs) such as soil grains on the ground surface, while the ground releases the heat stored during the day by radiation through the pores between HIPs and warms the air immediately above the surface at night. This “HIP hypothesis” can also account for the so-called “raised minimum (RM)” phenomenon. (author)

  18. Calming and Focusing: Students' Perceptions of Short Classroom Strategies for Fostering Presence.

    Science.gov (United States)

    VanKuiken, Debra; Bradley, Jennifer; Harland, Barbara; King, Margaret O'Brien

    2016-05-05

    Presence is the essence of professional nursing in the nurse-patient connection. Nursing students have little exposure to strategies fostering presence. This pilot study explored students' perceptions of strategies to encourage presence in the classroom. A three-question survey was distributed to students in the last week of classes. Faculty not teaching that course administered the survey. Four faculty used strategies aimed at encouraging presence. These strategies included starting class with a mindfulness minute, mindful movement, singing bowl, peace and power check in, and a discussion of a current event. Each class used only one strategy consistently through the semester. Participants were undergraduate and graduate students enrolled in one of seven classes taught by these faculty. Overall the students found strategies to be beneficial. In reflecting on the experience with the strategies, four themes emerged: calming/relaxing; focusing/centering; setting aside distractions; and feeling community and connection. These brief strategies were acceptable to most students and were helpful to the students in preparing for class. The response to mindfulness minute was most positive. Further research is needed on the introduction of strategies that help students in the classroom and may also increase presence at the bedside. © The Author(s) 2016.

  19. Loss restlessness and gain calmness: durable effects of losses and gains on choice switching.

    Science.gov (United States)

    Yechiam, Eldad; Zahavi, Gal; Arditi, Eli

    2015-08-01

    While the traditional conceptualization of the effect of losses focuses on bias in the subjective weight of losses compared with respective gains, some accounts suggest more global task-related effects of losses. Based on a recent attentional theory, we predicted a positive after-effect of losses on choice switching in later tasks. In two experimental studies, we found increased choice switching rates in tasks with losses compared to tasks with no losses. Additionally, this heightened shifting behavior was maintained in subsequent tasks that do not include losses, a phenomenon we refer to as "loss restlessness." Conversely, gains were found to have an opposite "calming" effect on choice switching. Surprisingly, the loss restlessness phenomenon was observed following an all-losses payoff regime but not after a task with symmetric mixed gains and losses. This suggests that the unresolved mental account following an all-losses regime increases search behavior. Potential implications to macro level phenomena, such as the leverage effect, are discussed.

  20. A Review of Apps for Calming, Relaxation, and Mindfulness Interventions for Pediatric Palliative Care Patients

    Directory of Open Access Journals (Sweden)

    Taelyr Weekly

    2018-01-01

    Full Text Available Patients and families increasingly use mobile apps as a relaxation and distraction intervention for children with complex, chronic medical conditions in the waiting room setting or during inpatient hospitalizations; and yet, there is limited data on app quality assessment or review of these apps for level of engagement, functionality, aesthetics, or applicability for palliative pediatric patients. The pediatric palliative care study team searched smartphone application platforms for apps relevant to calming, relaxation, and mindfulness for pediatric and adolescent patients. Apps were reviewed using a systematic data extraction tool. Validated Mobile Application Rating Scale (MARS scores were determined by two blinded reviewers. Apps were then characterized by infant, child, adolescent, and adult caregiver group categories. Reviewer discussion resulted in consensus. Sixteen of the 22 apps identified were included in the final analysis. The apps operated on either iOS or Android platforms. All were available in English with four available in Spanish. Apps featured a relaxation approach (12/16, soothing images (8/16, and breathing techniques (8/16. Mood and sleep patterns were the main symptoms targeted by apps. Provision of mobile apps resource summary has the potential to foster pediatric palliative care providers’ knowledge of app functionality and applicability as part of ongoing patient care.

  1. Low Voltage CMOS Fully Differential Current Feedback Amplifier with Controllable 3-dB Bandwidth

    International Nuclear Information System (INIS)

    Madian, A.H.; Mahmoud, S.A.; Ashour, M.A.; Soliman, A.M.

    2008-01-01

    This paper presents a new CMOS fully differential current feedback operational amplifier with controllable 3-dB bandwidth suitable for analog data processing and acquisition applications. The FDCFOA has the advantage of a wide range controllable 3-dB bandwidth (∼57 MHz to 500 MHz) without changing the feedback resistance this guarantee the stability of the circuit. The FDCFOA has a standby current of 320μA. PSpice simulations of the FDCFOA block were given using 0.25μm CMOS technology from AMI MOSIS and dual supply voltages ±0.75 V

  2. Apical control of xylem formation in the pine stem. II. Responses of differentiating tracheids

    Directory of Open Access Journals (Sweden)

    Jarosław Porandowski

    2014-01-01

    Full Text Available The effect of auxin supplied to the main stem of 5-year-old Pinus silvestris trees during various periods after decapitation upon differentiation of the secondary xylem tracheids was investigated. The results revealed the complexity of auxin involvement in the regulatory system of tracheid differentiation of secondary xylem. It is manifested both as the inductive effect to which the cells respond in the meristematic phase and in the continuous control during the consecutive stages of radial growth and maturation. A lack of auxin during the meristematic phase resulted in smaller cell diameters and reduced the daily rate of cell wall deposition even though these cells progressively grew and matured in the presence of auxin. The intensity of these two processes increased and the cells deposited thicker walls when auxin was supplied during all stages of tracheid differentiation even though the period of maturation decreased. Under these conditions tracheids of compression wood type differentiated. Continuous availability of auxin causes earlier termination of tracheid maturation while lack of auxin results in a delay of autolysis of protoplasts. In this case auxin probably functions in a system specifying information concerning the position of the cells in respect to the cambial layer.

  3. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA.

    KAUST Repository

    Cesana, Marcella

    2011-10-01

    Recently, a new regulatory circuitry has been identified in which RNAs can crosstalk with each other by competing for shared microRNAs. Such competing endogenous RNAs (ceRNAs) regulate the distribution of miRNA molecules on their targets and thereby impose an additional level of post-transcriptional regulation. Here we identify a muscle-specific long noncoding RNA, linc-MD1, which governs the time of muscle differentiation by acting as a ceRNA in mouse and human myoblasts. Downregulation or overexpression of linc-MD1 correlate with retardation or anticipation of the muscle differentiation program, respectively. We show that linc-MD1 "sponges" miR-133 and miR-133 [corrected] to regulate the expression of MAML1 and MEF2C, transcription factors that activate muscle-specific gene expression. Finally, we demonstrate that linc-MD1 exerts the same control over differentiation timing in human myoblasts, and that its levels are strongly reduced in Duchenne muscle cells. We conclude that the ceRNA network plays an important role in muscle differentiation.

  4. A long noncoding RNA controls muscle differentiation by functioning as a competing endogenous RNA.

    KAUST Repository

    Cesana, Marcella; Cacchiarelli, Davide; Legnini, Ivano; Santini, Tiziana; Sthandier, Olga; Chinappi, Mauro; Tramontano, Anna; Bozzoni, Irene

    2011-01-01

    Recently, a new regulatory circuitry has been identified in which RNAs can crosstalk with each other by competing for shared microRNAs. Such competing endogenous RNAs (ceRNAs) regulate the distribution of miRNA molecules on their targets and thereby impose an additional level of post-transcriptional regulation. Here we identify a muscle-specific long noncoding RNA, linc-MD1, which governs the time of muscle differentiation by acting as a ceRNA in mouse and human myoblasts. Downregulation or overexpression of linc-MD1 correlate with retardation or anticipation of the muscle differentiation program, respectively. We show that linc-MD1 "sponges" miR-133 and miR-133 [corrected] to regulate the expression of MAML1 and MEF2C, transcription factors that activate muscle-specific gene expression. Finally, we demonstrate that linc-MD1 exerts the same control over differentiation timing in human myoblasts, and that its levels are strongly reduced in Duchenne muscle cells. We conclude that the ceRNA network plays an important role in muscle differentiation.

  5. Novel adaptive neural control of flexible air-breathing hypersonic vehicles based on sliding mode differentiator

    Directory of Open Access Journals (Sweden)

    Bu Xiangwei

    2015-08-01

    Full Text Available A novel adaptive neural control strategy is exploited for the longitudinal dynamics of a generic flexible air-breathing hypersonic vehicle (FAHV. By utilizing functional decomposition method, the dynamics of FAHV is decomposed into the velocity subsystem and the altitude subsystem. For each subsystem, only one neural network is employed for the unknown function approximation. To further reduce the computational burden, minimal-learning parameter (MLP technology is used to estimate the norm of ideal weight vectors rather than their elements. By introducing sliding mode differentiator (SMD to estimate the newly defined variables, there is no need for the strict-feedback form and virtual controller. Hence the developed control law is considerably simpler than the ones derived from back-stepping scheme. Finally, simulation studies are made to illustrate the effectiveness of the proposed control approach in spite of the flexible effects, system uncertainties and varying disturbances.

  6. Neural mechanisms of attentional control differentiate trait and state negative affect

    Directory of Open Access Journals (Sweden)

    Laura D. Crocker

    2012-08-01

    Full Text Available The present research examined the hypothesis that cognitive processes are modulated differentially by trait and state negative affect (NA. Brain activation associated with trait and state NA was measured by fMRI during an attentional control task, the emotion-word Stroop. Performance on the task was disrupted only by state NA. Trait NA was associated with reduced activity in several regions, including a prefrontal area that has been shown to be involved in top-down, goal-directed attentional control. In contrast, state NA was associated with increased activity in several regions, including a prefrontal region that has been shown to be involved in stimulus-driven aspects of attentional control. Results suggest that NA has a significant impact on cognition, and that state and trait NA disrupt attentional control in distinct ways.

  7. Neural mechanisms of attentional control differentiate trait and state negative affect.

    Science.gov (United States)

    Crocker, Laura D; Heller, Wendy; Spielberg, Jeffrey M; Warren, Stacie L; Bredemeier, Keith; Sutton, Bradley P; Banich, Marie T; Miller, Gregory A

    2012-01-01

    The present research examined the hypothesis that cognitive processes are modulated differentially by trait and state negative affect (NA). Brain activation associated with trait and state NA was measured by fMRI during an attentional control task, the emotion-word Stroop. Performance on the task was disrupted only by state NA. Trait NA was associated with reduced activity in several regions, including a prefrontal area that has been shown to be involved in top-down, goal-directed attentional control. In contrast, state NA was associated with increased activity in several regions, including a prefrontal region that has been shown to be involved in stimulus-driven aspects of attentional control. Results suggest that NA has a significant impact on cognition, and that state and trait NA disrupt attentional control in distinct ways.

  8. Control of treatment of differentiated thyroid carcinoma by measurement of thyroglobulin in serum

    International Nuclear Information System (INIS)

    Hagemann, J.; Schneider, C.

    1978-01-01

    The presence of thyroglobulin in serum of patients with differentiated thyroid carcinoma was studied by a specific radioimmunoassay. Seventy-three patients with thyroid carcinomata were examined, 16 of whom had pulmonary or skeletal metastase, 11 local metastases, and the others no metastases. Patients with generalized metastases had very high serum thyroglobulin concentrations while those with local metastases had slightly elevated or normal concentrations. Those with remaining thyroid tissue had mainly normal thyroglobulin levels and patients with neither metastases nor remaining thyroid tissue had undetectable serum thyroglobulin. In seven patients with metastases it was possible to observe the development of serum thyroglobulin after 131 I treatment. In all cases the serum thyroglobulin concentration paralleled the development of the clinical status. Elevated serum thyroglobulin was also found in benign thyroid diseases such as hyperthyroidism and endemic goitre. Measurement of thyroglobulin in serum is therefore of little value in differentiating between benign and malignant thyroid diseases, but it is a good method for the follow-up control of patients with differentiated thyroid carcinomata. Because normal thyroglobulin levels do not exclude local metastases, additional examinations are necessary if normal thyroglobulin levels are found. When thyroglobulin is undetectable, metastases can be excluded and the measurement of thyroglobulin in serum can replace all other methods in the follow-up control. (author)

  9. Unkempt is negatively regulated by mTOR and uncouples neuronal differentiation from growth control.

    Directory of Open Access Journals (Sweden)

    Amélie Avet-Rochex

    2014-09-01

    Full Text Available Neuronal differentiation is exquisitely controlled both spatially and temporally during nervous system development. Defects in the spatiotemporal control of neurogenesis cause incorrect formation of neural networks and lead to neurological disorders such as epilepsy and autism. The mTOR kinase integrates signals from mitogens, nutrients and energy levels to regulate growth, autophagy and metabolism. We previously identified the insulin receptor (InR/mTOR pathway as a critical regulator of the timing of neuronal differentiation in the Drosophila melanogaster eye. Subsequently, this pathway has been shown to play a conserved role in regulating neurogenesis in vertebrates. However, the factors that mediate the neurogenic role of this pathway are completely unknown. To identify downstream effectors of the InR/mTOR pathway we screened transcriptional targets of mTOR for neuronal differentiation phenotypes in photoreceptor neurons. We identified the conserved gene unkempt (unk, which encodes a zinc finger/RING domain containing protein, as a negative regulator of the timing of photoreceptor differentiation. Loss of unk phenocopies InR/mTOR pathway activation and unk acts downstream of this pathway to regulate neurogenesis. In contrast to InR/mTOR signalling, unk does not regulate growth. unk therefore uncouples the role of the InR/mTOR pathway in neurogenesis from its role in growth control. We also identified the gene headcase (hdc as a second downstream regulator of the InR/mTOR pathway controlling the timing of neurogenesis. Unk forms a complex with Hdc, and Hdc expression is regulated by unk and InR/mTOR signalling. Co-overexpression of unk and hdc completely suppresses the precocious neuronal differentiation phenotype caused by loss of Tsc1. Thus, Unk and Hdc are the first neurogenic components of the InR/mTOR pathway to be identified. Finally, we show that Unkempt-like is expressed in the developing mouse retina and in neural stem

  10. Differential calorimeter and temperature controller for stored energy measurements in irradiated alkali halides

    International Nuclear Information System (INIS)

    Delgado Martinez, L.

    1977-01-01

    The design and performance of a simple temperature-controlled differential calorimeter are presented. This system allows to measure radiation-induced stored energy in insulators, above room temperature with a differential thermal analysis method. With platelets of KC1 single crystals, the base lines obtained for T 2 T 1 (with T 2 : irradiated sample temperature and T 1 : reference sample temperature) show a smooth drift less of 0,2 degree centigree in the interval from 25 to 400 degree centigree. The discrepancy between two consecutive base lines is less than ± 0,02 degree centigree which implies a calorimeter sensitivity of about ±0,004 cal/g. This sensitivity allows to measure stored energy release in samples with a color center concentration low enough to be directly measured with a spectrophotometer so that a search for correlations among the features of the stored energy spectrum and the color center annealing can be made. (Author) 13 refs

  11. The Role of Alternative Splicing in the Control of Immune Homeostasis and Cellular Differentiation.

    Science.gov (United States)

    Yabas, Mehmet; Elliott, Hannah; Hoyne, Gerard F

    2015-12-22

    Alternative splicing of pre-mRNA helps to enhance the genetic diversity within mammalian cells by increasing the number of protein isoforms that can be generated from one gene product. This provides a great deal of flexibility to the host cell to alter protein function, but when dysregulation in splicing occurs this can have important impact on health and disease. Alternative splicing is widely used in the mammalian immune system to control the development and function of antigen specific lymphocytes. In this review we will examine the splicing of pre-mRNAs yielding key proteins in the immune system that regulate apoptosis, lymphocyte differentiation, activation and homeostasis, and discuss how defects in splicing can contribute to diseases. We will describe how disruption to trans-acting factors, such as heterogeneous nuclear ribonucleoproteins (hnRNPs), can impact on cell survival and differentiation in the immune system.

  12. Differential evolution algorithm based automatic generation control for interconnected power systems with

    Directory of Open Access Journals (Sweden)

    Banaja Mohanty

    2014-09-01

    Full Text Available This paper presents the design and performance analysis of Differential Evolution (DE algorithm based Proportional–Integral (PI and Proportional–Integral–Derivative (PID controllers for Automatic Generation Control (AGC of an interconnected power system. Initially, a two area thermal system with governor dead-band nonlinearity is considered for the design and analysis purpose. In the proposed approach, the design problem is formulated as an optimization problem control and DE is employed to search for optimal controller parameters. Three different objective functions are used for the design purpose. The superiority of the proposed approach has been shown by comparing the results with a recently published Craziness based Particle Swarm Optimization (CPSO technique for the same interconnected power system. It is noticed that, the dynamic performance of DE optimized PI controller is better than CPSO optimized PI controllers. Additionally, controller parameters are tuned at different loading conditions so that an adaptive gain scheduling control strategy can be employed. The study is further extended to a more realistic network of two-area six unit system with different power generating units such as thermal, hydro, wind and diesel generating units considering boiler dynamics for thermal plants, Generation Rate Constraint (GRC and Governor Dead Band (GDB non-linearity.

  13. No Calm After the Storm: A Systematic Review of Human Health Following Flood and Storm Disasters.

    Science.gov (United States)

    Saulnier, Dell D; Brolin Ribacke, Kim; von Schreeb, Johan

    2017-10-01

    Introduction How the burden of disease varies during different phases after floods and after storms is essential in order to guide a medical response, but it has not been well-described. The objective of this review was to elucidate the health problems following flood and storm disasters. A literature search of the databases Medline (US National Library of Medicine, National Institutes of Health; Bethesda, Maryland USA); Cinahl (EBSCO Information Services; Ipswich, Massachusetts USA); Global Health (EBSCO Information Services; Ipswich, Massachusetts USA); Web of Science Core Collection (Thomson Reuters; New York, New York USA); Embase (Elsevier; Amsterdam, Netherlands); and PubMed (National Center for Biotechnology Information, National Institutes of Health; Bethesda, Maryland USA) was conducted in June 2015 for English-language research articles on morbidity or mortality and flood or storm disasters. Articles on mental health, interventions, and rescue or health care workers were excluded. Data were extracted from articles that met the eligibility criteria and analyzed by narrative synthesis. The review included 113 studies. Poisonings, wounds, gastrointestinal infections, and skin or soft tissue infections all increased after storms. Gastrointestinal infections were more frequent after floods. Leptospirosis and diabetes-related complications increased after both. The majority of changes occurred within four weeks of floods or storms. Health changes differently after floods and after storms. There is a lack of data on the health effects of floods alone, long-term changes in health, and the strength of the association between disasters and health problems. This review highlights areas of consideration for medical response and the need for high-quality, systematic research in this area. Saulnier DD , Brolin Ribacke K , von Schreeb J . No calm after the storm: a systematic review of human health following flood and storm disasters. Prehosp Disaster Med. 2017;32(5):568-579.

  14. Optimum differential terms for lateral motion control performance on the vehicle; Yokoundo seigyo seino ni oyobosu hisenkei bibunko no saitekika

    Energy Technology Data Exchange (ETDEWEB)

    Miyamori, A [Japan Consumer Information Center, Tokyo (Japan); Nakaya, H [Shibaura Institute of Technology, Tokyo (Japan)

    1997-10-01

    As general knowledge, the lateral control performance of vehicle improves as differential terms increases. But subjective rating has its limits of effect. The coefficient of differential terms and saturated steer angle velocity were set up using the experimental vehicle in several steps. Consequently, the optimum range, that subjective and objective rating were compatible, were made clear. 4 refs., 6 figs., 1 tab.

  15. Adaptive Neural Control of Nonaffine Nonlinear Systems without Differential Condition for Nonaffine Function

    Directory of Open Access Journals (Sweden)

    Chaojiao Sun

    2016-01-01

    Full Text Available An adaptive neural control scheme is proposed for nonaffine nonlinear system without using the implicit function theorem or mean value theorem. The differential conditions on nonaffine nonlinear functions are removed. The control-gain function is modeled with the nonaffine function probably being indifferentiable. Furthermore, only a semibounded condition for nonaffine nonlinear function is required in the proposed method, and the basic idea of invariant set theory is then constructively introduced to cope with the difficulty in the control design for nonaffine nonlinear systems. It is rigorously proved that all the closed-loop signals are bounded and the tracking error converges to a small residual set asymptotically. Finally, simulation examples are provided to demonstrate the effectiveness of the designed method.

  16. Magnetic-field-controlled negative differential conductance in scanning tunneling spectroscopy of graphene npn junction resonators

    Science.gov (United States)

    Li, Si-Yu; Liu, Haiwen; Qiao, Jia-Bin; Jiang, Hua; He, Lin

    2018-03-01

    Negative differential conductance (NDC), characterized by the decreasing current with increasing voltage, has attracted continuous attention for its various novel applications. The NDC typically exists in a certain range of bias voltages for a selected system and controlling the regions of NDC in curves of current versus voltage (I -V ) is experimentally challenging. Here, we demonstrate a magnetic-field-controlled NDC in scanning tunneling spectroscopy of graphene npn junction resonators. The magnetic field not only can switch on and off the NDC, but also can continuously tune the regions of the NDC in the I -V curves. In the graphene npn junction resonators, magnetic fields generate sharp and pronounced Landau-level peaks with the help of the Klein tunneling of massless Dirac fermions. A tip of scanning tunneling microscope induces a relatively shift of the Landau levels in graphene beneath the tip. Tunneling between the misaligned Landau levels results in the magnetic-field-controlled NDC.

  17. Differentiating Patients with Parkinson's Disease from Normal Controls Using Gray Matter in the Cerebellum.

    Science.gov (United States)

    Zeng, Ling-Li; Xie, Liang; Shen, Hui; Luo, Zhiguo; Fang, Peng; Hou, Yanan; Tang, Beisha; Wu, Tao; Hu, Dewen

    2017-02-01

    Parkinson's disease (PD) is one of the most common neurodegenerative disorders in the world. Previous studies have focused on the basal ganglia and cerebral cortices. To date, the cerebellum has not been systematically investigated in patients with PD. In the current study, 45 probable PD patients and 40 age- and gender-matched healthy controls underwent structural magnetic resonance imaging, and we used support vector machines combining with voxel-based morphometry to explore the cerebellar structural changes in the probable PD patients relative to healthy controls. The results revealed that the gray matter alterations were primarily located within the cerebellar Crus I, implying a possible important role of this region in PD. Furthermore, the gray matter alterations in the cerebellum could differentiate the probable PD patients from healthy controls with accuracies of more than 95 % (p cerebellum in the clinical diagnosis of PD.

  18. Effective connectivity within the frontoparietal control network differentiates cognitive control and working memory.

    Science.gov (United States)

    Harding, Ian H; Yücel, Murat; Harrison, Ben J; Pantelis, Christos; Breakspear, Michael

    2015-02-01

    Cognitive control and working memory rely upon a common fronto-parietal network that includes the inferior frontal junction (IFJ), dorsolateral prefrontal cortex (dlPFC), pre-supplementary motor area/dorsal anterior cingulate cortex (pSMA/dACC), and intraparietal sulcus (IPS). This network is able to flexibly adapt its function in response to changing behavioral goals, mediating a wide range of cognitive demands. Here we apply dynamic causal modeling to functional magnetic resonance imaging data to characterize task-related alterations in the strength of network interactions across distinct cognitive processes. Evidence in favor of task-related connectivity dynamics was accrued across a very large space of possible network structures. Cognitive control and working memory demands were manipulated using a factorial combination of the multi-source interference task and a verbal 2-back working memory task, respectively. Both were found to alter the sensitivity of the IFJ to perceptual information, and to increase IFJ-to-pSMA/dACC connectivity. In contrast, increased connectivity from the pSMA/dACC to the IPS, as well as from the dlPFC to the IFJ, was uniquely driven by cognitive control demands; a task-induced negative influence of the dlPFC on the pSMA/dACC was specific to working memory demands. These results reflect a system of both shared and unique context-dependent dynamics within the fronto-parietal network. Mechanisms supporting cognitive engagement, response selection, and action evaluation may be shared across cognitive domains, while dynamic updating of task and context representations within this network are potentially specific to changing demands on cognitive control. Copyright © 2014 Elsevier Inc. All rights reserved.

  19. Planar Cell Polarity Controls Pancreatic Beta Cell Differentiation and Glucose Homeostasis

    Directory of Open Access Journals (Sweden)

    Cedric Cortijo

    2012-12-01

    Full Text Available Planar cell polarity (PCP refers to the collective orientation of cells within the epithelial plane. We show that progenitor cells forming the ducts of the embryonic pancreas express PCP proteins and exhibit an active PCP pathway. Planar polarity proteins are acquired at embryonic day 11.5 synchronously to apicobasal polarization of pancreas progenitors. Loss of function of the two PCP core components Celsr2 and Celsr3 shows that they control the differentiation of endocrine cells from polarized progenitors, with a prevalent effect on insulin-producing beta cells. This results in a decreased glucose clearance. Loss of Celsr2 and 3 leads to a reduction of Jun phosphorylation in progenitors, which, in turn, reduces beta cell differentiation from endocrine progenitors. These results highlight the importance of the PCP pathway in cell differentiation in vertebrates. In addition, they reveal that tridimensional organization and collective communication of cells are needed in the pancreatic epithelium in order to generate appropriate numbers of endocrine cells.

  20. Wnt control of stem cells and differentiation in the intestinal epithelium

    International Nuclear Information System (INIS)

    Pinto, Daniel; Clevers, Hans

    2005-01-01

    The intestinal epithelium represents a very attractive experimental model for the study of integrated key cellular processes such as proliferation and differentiation. The tissue is subjected to a rapid and perpetual self-renewal along the crypt-villus axis. Renewal requires division of multipotent stem cells, still to be morphologically identified and isolated, followed by transit amplification, and differentiation of daughter cells into specialized absorptive and secretory cells. Our understanding of the crucial role played by the Wnt/β-catenin signaling pathway in controlling the fine balance between cell proliferation and differentiation in the gut has been significantly enhanced in recent years. Mutations in some of its components irreversibly lead to carcinogenesis in humans and in mice. Here, we discuss recent advances related to the Wnt/β-catenin signaling pathway in regulating intestinal stem cells, homeostasis, and cancer. We emphasize how Wnt signaling is able to maintain a stem cell/progenitor phenotype in normal intestinal crypts, and to impose a very similar phenotype onto colorectal adenomas

  1. Prokineticin receptor 1 as a novel suppressor of preadipocyte proliferation and differentiation to control obesity.

    Directory of Open Access Journals (Sweden)

    Cécilia Szatkowski

    Full Text Available BACKGROUND: Adipocyte renewal from preadipocytes occurs throughout the lifetime and contributes to obesity. To date, little is known about the mechanisms that control preadipocyte proliferation and differentiation. Prokineticin-2 is an angiogenic and anorexigenic hormone that activate two G protein-coupled receptors (GPCRs: PKR1 and PKR2. Prokineticin-2 regulates food intake and energy metabolism via central mechanisms (PKR2. The peripheral effect of prokineticin-2 on adipocytes/preadipocytes has not been studied yet. METHODOLOGY/PRINCIPAL FINDINGS: Since adipocytes and preadipocytes express mainly prokineticin receptor-1 (PKR1, here, we explored the role of PKR1 in adipose tissue expansion, generating PKR1-null (PKR1(-/- and adipocyte-specific (PKR1(ad-/- mutant mice, and using murine and human preadipocyte cell lines. Both PKR1(-/- and PKR1(ad-/- had excessive abdominal adipose tissue, but only PKR1(-/- mice showed severe obesity and diabetes-like syndrome. PKR1(ad-/- mice had increased proliferating preadipocytes and newly formed adipocyte levels, leading to expansion of adipose tissue. Using PKR1-knockdown in 3T3-L1 preadipocytes, we show that PKR1 directly inhibits preadipocyte proliferation and differentiation. These PKR1 cell autonomous actions appear targeted at preadipocyte cell cycle regulatory pathways, through reducing cyclin D, E, cdk2, c-Myc levels. CONCLUSIONS/SIGNIFICANCE: These results suggest PKR1 to be a crucial player in the preadipocyte proliferation and differentiation. Our data should facilitate studies of both the pathogenesis and therapy of obesity in humans.

  2. Tuning of Controller for Type 1 Diabetes Treatment with Stochastic Differential Equations

    DEFF Research Database (Denmark)

    Duun-Henriksen, Anne Katrine; Boiroux, Dimitri; Schmidt, Signe

    2012-01-01

    due to the noise corrupted observations from the CGM. In this paper we present a method to estimate the optimal Kalman gain in the controller based on stochastic differential equation modeling. With this model type we could estimate the process noise and observation noise separately based on data from......People with type 1 diabetes need several insulin injections every day to keep their blood glucose level in the normal range and thereby avoiding the acute and long term complications of diabetes. One of the recent treatments consists of a pump injecting insulin into the subcutaneous layer combined...

  3. Numerical Oscillations Analysis for Nonlinear Delay Differential Equations in Physiological Control Systems

    Directory of Open Access Journals (Sweden)

    Qi Wang

    2012-01-01

    Full Text Available This paper deals with the oscillations of numerical solutions for the nonlinear delay differential equations in physiological control systems. The exponential θ-method is applied to p′(t=β0ωμp(t−τ/(ωμ+pμ(t−τ−γp(t and it is shown that the exponential θ-method has the same order of convergence as that of the classical θ-method. Several conditions under which the numerical solutions oscillate are derived. Moreover, it is proven that every nonoscillatory numerical solution tends to positive equilibrium of the continuous system. Finally, the main results are illustrated with numerical examples.

  4. A numerical technique for solving fractional optimal control problems and fractional Riccati differential equations

    Directory of Open Access Journals (Sweden)

    F. Ghomanjani

    2016-10-01

    Full Text Available In the present paper, we apply the Bezier curves method for solving fractional optimal control problems (OCPs and fractional Riccati differential equations. The main advantage of this method is that it can reduce the error of the approximate solutions. Hence, the solutions obtained using the Bezier curve method give good approximations. Some numerical examples are provided to confirm the accuracy of the proposed method. All of the numerical computations have been performed on a PC using several programs written in MAPLE 13.

  5. Airline seat inventory control benefiting from currency differentials to enhance revenues

    Directory of Open Access Journals (Sweden)

    C.E. Love

    2003-12-01

    Full Text Available The purpose of this paper is to develop an airline seat inventory control model which will capitalise on currency differentials that exist between city pairs. The approach taken here is to maximise Expected Marginal Seat Revenues as proposed by Belobaba for non-nested fare classes. the basic Expected Marginal Seat Revenue model is extended to explicitly include the effects of overbooking. Data from the South African Airways return flight between Cape Town and London is utilised to demonstrate the model.

  6. An analytical investigation on the valve and centrifugal pump speed control with a constant differential pressure across the valve

    International Nuclear Information System (INIS)

    Jung, B. R.; Joo, K. I.; Lee, B. J.; Baek, S. J.; Noh, T. S.

    2003-01-01

    A valve opening and centrifugal pump speed control was investigated analytically in a simple pumping system where the differential pressure across the control valve is maintained constant over the required flow range. The valve control program was derived analytically only as a function of the required flow rate to maintain the constant differential pressure across the valve. The centrifugal pump speed control program was also derived analytically for the required flow rate for the constant differential pressure across the control valve. These derivations theoretically show that the independent control is possible between the valve and pump speed in a system with a constant valve pressure drop. In addition, it was shown that a linear pump speed control is impossible in maintaining the constant valve pressure drop

  7. Psychosocial risk factors which may differentiate between women with Functional Voice Disorder, Organic Voice Disorder and a Control group.

    Science.gov (United States)

    Baker, Janet; Ben-Tovim, David; Butcher, Andrew; Esterman, Adrian; McLaughlin, Kristin

    2013-12-01

    This study aimed to explore psychosocial factors contributing to the development of functional voice disorders (FVD) and those differentiating between organic voice disorders (OVD) and a non-voice-disordered control group. A case-control study was undertaken of 194 women aged 18-80 years diagnosed with FVD (n = 73), OVD (n = 55), and controls (n = 66). FVD women were allocated into psychogenic voice disorder (PVD) (n = 37) and muscle tension voice disorder (MTVD) (n = 36) for sub-group analysis. Dependent variables included biographical and voice assessment data, the number and severity of life events and difficulties and conflict over speaking out (COSO) situations derived from the Life Events and Difficulties Schedule (LEDS), and psychological traits including emotional expressiveness scales. Four psychosocial components differentiated between the FVD and control group accounting for 84.9% of the variance: severe events, moderate events, severe COSO, and mild COSO difficulties. Severe events, severe and mild COSO difficulties differentiated between FVD and OVD groups, accounting for 80.5% of the variance. Moderate events differentiated between PVD and MTVD sub-groups, accounting for 58.9% of the variance. Psychological traits did not differentiate between groups. Stressful life events and COSO situations best differentiated FVD from OVD and control groups. More refined aetiological studies are needed to differentiate between PVD and MTVD.

  8. Differential flatness properties and adaptive control of the hypothalamic-pituitary-adrenal axis model

    Science.gov (United States)

    Rigatos, Gerasimos

    2016-12-01

    It is shown that the model of the hypothalamic-pituitary-adrenal gland axis is a differentially flat one and this permits to transform it to the so-called linear canonical form. For the new description of the system's dynamics the transformed control inputs contain unknown terms which depend on the system's parameters. To identify these terms an adaptive fuzzy approximator is used in the control loop. Thus an adaptive fuzzy control scheme is implemented in which the unknown or unmodeled system dynamics is approximated by neurofuzzy networks and next this information is used by a feedback controller that makes the state variables (CRH - corticotropin releasing hormone, adenocortocotropic hormone - ACTH, cortisol) of the hypothalamic-pituitary-adrenal gland axis model converge to the desirable levels (setpoints). This adaptive control scheme is exclusively implemented with the use of output feedback, while the state vector elements which are not directly measured are estimated with the use of a state observer that operates in the control loop. The learning rate of the adaptive fuzzy system is suitably computed from Lyapunov analysis, so as to assure that both the learning procedure for the unknown system's parameters, the dynamics of the observer and the dynamics of the control loop will remain stable. The performed Lyapunov stability analysis depends on two Riccati equations, one associated with the feedback controller and one associated with the state observer. Finally, it is proven that for the control scheme that comprises the feedback controller, the state observer and the neurofuzzy approximator, an H-infinity tracking performance can be succeeded.

  9. A Bilayer Construct Controls Adipose-Derived Stem Cell Differentiation into Endothelial Cells and Pericytes without Growth Factor Stimulation

    Science.gov (United States)

    2011-01-01

    A Bilayer Construct Controls Adipose-Derived Stem Cell Differentiation into Endothelial Cells and Pericytes Without Growth Factor Stimulation...Ph.D.3 This work describes the differentiation of adipose-derived mesenchymal stem cells (ASC) in a composite hy- drogel for use as a vascularized...tissue from a single population of ASC. This work underscores the importance of the extracellular matrix in controlling stem cell phenotype. It is our

  10. Introduction of N-cadherin-binding motif to alginate hydrogels for controlled stem cell differentiation.

    Science.gov (United States)

    Lee, Jae Won; An, Hyoseok; Lee, Kuen Yong

    2017-07-01

    Control of stem cell fate and phenotype using biomimetic synthetic extracellular matrices (ECMs) is an important tissue engineering approach. Many studies have focused on improving cell-matrix interactions. However, proper control of cell-cell interactions using synthetic ECMs could be critical for tissue engineering, especially with undifferentiated stem cells. In this study, alginate hydrogels were modified with a peptide derived from the low-density lipoprotein receptor-related protein 5 (LRP5), which is known to bind to N-cadherin, as a cell-cell interaction motif. In vitro changes in the morphology and differentiation of mouse bone marrow stromal cells (D1 stem cells) cultured in LRP5-alginate hydrogels were investigated. LRP5-alginate gels successfully induced stem cell aggregation and enhanced chondrogenic differentiation of D1 stem cells, compared to RGD-alginate gels, at low cell density. This approach to tailoring synthetic biomimetic ECMs using cell-cell interaction motifs may be critical in tissue engineering approaches using stem cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. On an integro-differential model for pest control in a heterogeneous environment.

    Science.gov (United States)

    Rodríguez, Nancy

    2015-04-01

    Insect pests pose a major threat to a balanced ecology as it can threaten local species as well as spread human diseases; thus, making the study of pest control extremely important. In practice, the sterile insect release method (SIRM), where a sterile population is introduced into the wild population with the aim of significantly reducing the growth of the population, has been a popular technique used to control pest invasions. In this work we introduce an integro-differential equation to model the propagation of pests in a heterogeneous environment, where this environment is divided into three regions. In one region SIRM is not used making this environment conducive to propagation of the insects. A second region is the eradication zone where there is an intense release of sterile insects, leading to decay of the population in this region. In the final region we explore two scenarios. In the first case, there is a small release of sterile insects and we prove that if the eradication zone is sufficiently large the pests will not invade. In the second case, when SIRM is not used at all in this region we show that invasions always occur regardless of the size of the eradication zone. Finally, we consider the limiting equation of the integro-differential equation and prove that in this case there is a critical length of the eradication zone which separates propagation from obstruction. Moreover, we provide some upper and lower bound for the critical length.

  12. Stochastic optimal control, forward-backward stochastic differential equations and the Schroedinger equation

    Energy Technology Data Exchange (ETDEWEB)

    Paul, Wolfgang; Koeppe, Jeanette [Institut fuer Physik, Martin Luther Universitaet, 06099 Halle (Germany); Grecksch, Wilfried [Institut fuer Mathematik, Martin Luther Universitaet, 06099 Halle (Germany)

    2016-07-01

    The standard approach to solve a non-relativistic quantum problem is through analytical or numerical solution of the Schroedinger equation. We show a way to go around it. This way is based on the derivation of the Schroedinger equation from conservative diffusion processes and the establishment of (several) stochastic variational principles leading to the Schroedinger equation under the assumption of a kinematics described by Nelson's diffusion processes. Mathematically, the variational principle can be considered as a stochastic optimal control problem linked to the forward-backward stochastic differential equations of Nelson's stochastic mechanics. The Hamilton-Jacobi-Bellmann equation of this control problem is the Schroedinger equation. We present the mathematical background and how to turn it into a numerical scheme for analyzing a quantum system without using the Schroedinger equation and exemplify the approach for a simple 1d problem.

  13. Sub-optimal control of fuzzy linear dynamical systems under granular differentiability concept.

    Science.gov (United States)

    Mazandarani, Mehran; Pariz, Naser

    2018-05-01

    This paper deals with sub-optimal control of a fuzzy linear dynamical system. The aim is to keep the state variables of the fuzzy linear dynamical system close to zero in an optimal manner. In the fuzzy dynamical system, the fuzzy derivative is considered as the granular derivative; and all the coefficients and initial conditions can be uncertain. The criterion for assessing the optimality is regarded as a granular integral whose integrand is a quadratic function of the state variables and control inputs. Using the relative-distance-measure (RDM) fuzzy interval arithmetic and calculus of variations, the optimal control law is presented as the fuzzy state variables feedback. Since the optimal feedback gains are obtained as fuzzy functions, they need to be defuzzified. This will result in the sub-optimal control law. This paper also sheds light on the restrictions imposed by the approaches which are based on fuzzy standard interval arithmetic (FSIA), and use strongly generalized Hukuhara and generalized Hukuhara differentiability concepts for obtaining the optimal control law. The granular eigenvalues notion is also defined. Using an RLC circuit mathematical model, it is shown that, due to their unnatural behavior in the modeling phenomenon, the FSIA-based approaches may obtain some eigenvalues sets that might be different from the inherent eigenvalues set of the fuzzy dynamical system. This is, however, not the case with the approach proposed in this study. The notions of granular controllability and granular stabilizability of the fuzzy linear dynamical system are also presented in this paper. Moreover, a sub-optimal control for regulating a Boeing 747 in longitudinal direction with uncertain initial conditions and parameters is gained. In addition, an uncertain suspension system of one of the four wheels of a bus is regulated using the sub-optimal control introduced in this paper. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

  14. Hippo/Yap signaling controls epithelial progenitor cell proliferation and differentiation in the embryonic and adult lung

    Science.gov (United States)

    Lange, Alexander W.; Sridharan, Anusha; Xu, Yan; Stripp, Barry R.; Perl, Anne-Karina; Whitsett, Jeffrey A.

    2015-01-01

    The Hippo/Yap pathway is a well-conserved signaling cascade that regulates cell proliferation and differentiation to control organ size and stem/progenitor cell behavior. Following airway injury, Yap was dynamically regulated in regenerating airway epithelial cells. To determine the role of Hippo signaling in the lung, the mammalian Hippo kinases, Mst1 and Mst2, were deleted in epithelial cells of the embryonic and mature mouse lung. Mst1/2 deletion in the fetal lung enhanced proliferation and inhibited sacculation and epithelial cell differentiation. The transcriptional inhibition of cell proliferation and activation of differentiation during normal perinatal lung maturation were inversely regulated following embryonic Mst1/2 deletion. Ablation of Mst1/2 from bronchiolar epithelial cells in the adult lung caused airway hyperplasia and altered differentiation. Inhibitory Yap phosphorylation was decreased and Yap nuclear localization and transcriptional targets were increased after Mst1/2 deletion, consistent with canonical Hippo/Yap signaling. YAP potentiated cell proliferation and inhibited differentiation of human bronchial epithelial cells in vitro. Loss of Mst1/2 and expression of YAP regulated transcriptional targets controlling cell proliferation and differentiation, including Ajuba LIM protein. Ajuba was required for the effects of YAP on cell proliferation in vitro. Hippo/Yap signaling regulates Ajuba and controls proliferation and differentiation of lung epithelial progenitor cells. PMID:25480985

  15. Control of heme synthesis during Friend cell differentiation: role of iron and transferrin

    International Nuclear Information System (INIS)

    Laskey, J.D.; Ponka, P.; Schulman, H.M.

    1986-01-01

    In many types of cells the synthesis of σ-aminolevulinic acid (ALA) limits the rate of heme formation. However, results from this laboratory with reticulocytes suggest that the rate of iron uptake from 125 I-transferrin (Tf), rather than ALA synthase activity, limits the rate of heme synthesis in erythroid cells. To determine whether changes occur in iron metabolism and the control of heme synthesis during erythroid cell development Friend erythroleukemia cells induced to erythroid differentiation by dimethylsulfoxide (DMSO) were studied. While added ALA stimulated heme synthesis in uninduced Friend cells (suggesting ALA synthase is limiting) it did not do so in induced cells. Therefore the possibility was investigated that, in induced cells, iron uptake from Tf limits and controls heme synthesis. Several aspects of iron metabolism were investigated using the synthetic iron chelator salicylaldehyde isonicotinoyl hydrazone (SIH). Both induced and uninduced Friend cells take up and utilize Fe for heme synthesis directly from Fe-SIH without the involvement of transferrin and transferrin receptors and to a much greater extent than from saturating levels or 59 Fe-Tf (20 μM). Furthermore, in induced Friend cells 100 μM Fe-SIH stimulated 2- 14 C-glycine incorporation into heme up to 3.6-fold as compared to the incorporation observed with saturating concentrations of Fe-Tf. These results indicate that some step(s) in the pathway of iron from extracellular Tf to protoporphyrin, rather than the activity of ALA synthase, limits and controls the overall rate of heme and possibly hemoglobin synthesis in differentiating Friend erythroleukemia cells

  16. Parallel factor ChIP provides essential internal control for quantitative differential ChIP-seq.

    Science.gov (United States)

    Guertin, Michael J; Cullen, Amy E; Markowetz, Florian; Holding, Andrew N

    2018-04-17

    A key challenge in quantitative ChIP combined with high-throughput sequencing (ChIP-seq) is the normalization of data in the presence of genome-wide changes in occupancy. Analysis-based normalization methods were developed for transcriptomic data and these are dependent on the underlying assumption that total transcription does not change between conditions. For genome-wide changes in transcription factor (TF) binding, these assumptions do not hold true. The challenges in normalization are confounded by experimental variability during sample preparation, processing and recovery. We present a novel normalization strategy utilizing an internal standard of unchanged peaks for reference. Our method can be readily applied to monitor genome-wide changes by ChIP-seq that are otherwise lost or misrepresented through analytical normalization. We compare our approach to normalization by total read depth and two alternative methods that utilize external experimental controls to study TF binding. We successfully resolve the key challenges in quantitative ChIP-seq analysis and demonstrate its application by monitoring the loss of Estrogen Receptor-alpha (ER) binding upon fulvestrant treatment, ER binding in response to estrodiol, ER mediated change in H4K12 acetylation and profiling ER binding in patient-derived xenographs. This is supported by an adaptable pipeline to normalize and quantify differential TF binding genome-wide and generate metrics for differential binding at individual sites.

  17. Transcription control and neuronal differentiation by agents that activate the LXR nuclear receptor family.

    Science.gov (United States)

    Schmidt, A; Vogel, R; Holloway, M K; Rutledge, S J; Friedman, O; Yang, Z; Rodan, G A; Friedman, E

    1999-09-10

    LXR and PPAR receptors belong to the nuclear receptor superfamily of transcriptional activating factors. Using ligand-dependent transcription assays, we found that 5-tetradecyloxy-2-furancarboxylic acid (TOFA) transactivates chimeric receptors composed of the glucocorticoid receptor DNA binding domain and the ligand binding regions of PPARalpha, PPARbeta (NUC-1) and LXRbeta (NER) receptors. In the same assays, ligands for PPARs (oleic acid, WY-14643 and L-631,033) and LXRs (hydroxycholesterols) maintain their respective receptor selectivity. TOFA and hydroxycholesterols also stimulate transcription from a minimal fibrinogen promoter that is under the control of AP-1 or NF-kappaB transcription factor binding sites. In addition to their effects on transcription, these LXRbeta activators induce neuronal differentiation in rat pheochromocytoma cells. TOFA and the natural LXR agonist, 22 (R)-hydroxycholesterol, stimulate neurite outgrowth in 55 and 28% of cells, respectively. No neurite outgrowth was induced by the related 22(S)-hydroxycholesterol, which does not activate the LXR family. These results suggest that the hydroxycholesterol signaling pathway has a complex effect on transcription that mediates the activity of TOFA and hydroxycholesterol on neuronal differentiation in pheochromocytoma cells.

  18. A molecular threshold for effector CD8(+) T cell differentiation controlled by transcription factors Blimp-1 and T-bet.

    Science.gov (United States)

    Xin, Annie; Masson, Frederick; Liao, Yang; Preston, Simon; Guan, Tianxia; Gloury, Renee; Olshansky, Moshe; Lin, Jian-Xin; Li, Peng; Speed, Terence P; Smyth, Gordon K; Ernst, Matthias; Leonard, Warren J; Pellegrini, Marc; Kaech, Susan M; Nutt, Stephen L; Shi, Wei; Belz, Gabrielle T; Kallies, Axel

    2016-04-01

    T cell responses are guided by cytokines that induce transcriptional regulators, which ultimately control differentiation of effector and memory T cells. However, it is unknown how the activities of these molecular regulators are coordinated and integrated during the differentiation process. Using genetic approaches and transcriptional profiling of antigen-specific CD8(+) T cells, we reveal a common program of effector differentiation that is regulated by IL-2 and IL-12 signaling and the combined activities of the transcriptional regulators Blimp-1 and T-bet. The loss of both T-bet and Blimp-1 leads to abrogated cytotoxic function and ectopic IL-17 production in CD8(+) T cells. Overall, our data reveal two major overlapping pathways of effector differentiation governed by the availability of Blimp-1 and T-bet and suggest a model for cytokine-induced transcriptional changes that combine, quantitatively and qualitatively, to promote robust effector CD8(+) T cell differentiation.

  19. Can Differentiated Production Planning and Control enable both Responsiveness and Efficiency in Food Production?

    Directory of Open Access Journals (Sweden)

    Anita Romsdal

    2014-07-01

    Full Text Available This paper addresses the complex production planning and control (PPC challenges in food supply chains. The study illustrates how food producers' traditional make‐to‐stock (MTS approach is not well suited to meet the trends of increasing product variety, higher demand uncertainty, increasing sales of fresh food products and more demanding customers. The paper proposes a framework for differentiated PPC that combines MTS with make‐to‐order (MTO.The framework matches products with the most appropriate PPC approaches and buffering techniques depending on market and product characteristics. The core idea is to achieve more volume flexibility in the production system by exploiting favourable product and market characteristics (high demand predictability, long customer order leadtime allowances and low product perishability. A case study is used to demonstrate how the framework can enable food producers to achieve efficiency in production, inventory and PPC processes – and simultaneously be responsive to market requirements.

  20. Robustness of Operational Matrices of Differentiation for Solving State-Space Analysis and Optimal Control Problems

    Directory of Open Access Journals (Sweden)

    Emran Tohidi

    2013-01-01

    Full Text Available The idea of approximation by monomials together with the collocation technique over a uniform mesh for solving state-space analysis and optimal control problems (OCPs has been proposed in this paper. After imposing the Pontryagins maximum principle to the main OCPs, the problems reduce to a linear or nonlinear boundary value problem. In the linear case we propose a monomial collocation matrix approach, while in the nonlinear case, the general collocation method has been applied. We also show the efficiency of the operational matrices of differentiation with respect to the operational matrices of integration in our numerical examples. These matrices of integration are related to the Bessel, Walsh, Triangular, Laguerre, and Hermite functions.

  1. Chaos Enhanced Differential Evolution in the Task of Evolutionary Control of Selected Set of Discrete Chaotic Systems

    Directory of Open Access Journals (Sweden)

    Roman Senkerik

    2014-01-01

    Full Text Available Evolutionary technique differential evolution (DE is used for the evolutionary tuning of controller parameters for the stabilization of set of different chaotic systems. The novelty of the approach is that the selected controlled discrete dissipative chaotic system is used also as the chaotic pseudorandom number generator to drive the mutation and crossover process in the DE. The idea was to utilize the hidden chaotic dynamics in pseudorandom sequences given by chaotic map to help differential evolution algorithm search for the best controller settings for the very same chaotic system. The optimizations were performed for three different chaotic systems, two types of case studies and developed cost functions.

  2. Differential Diagnosis of Autism Spectrum Disorder and Attention Deficit Hyperactivity Disorder by Means of Inhibitory Control and "Theory of Mind"

    Science.gov (United States)

    Buhler, Eva; Bachmann, Christian; Goyert, Hannah; Heinzel-Gutenbrunner, Monika; Kamp-Becker, Inge

    2011-01-01

    Autism spectrum disorders (ASD) and attention deficit hyperactivity disorders (ADHD) are both associated with deficits in executive control and with problems in social contexts. This study analyses the variables inhibitory control and theory of mind (ToM), including a developmental aspect in the case of the latter, to differentiate between the…

  3. Dynamics and control for Constrained Multibody Systems modeled with Maggi's equation: Application to Differential Mobile Robots Partll

    International Nuclear Information System (INIS)

    Amengonu, Yawo H; Kakad, Yogendra P

    2014-01-01

    Quasivelocity techniques were applied to derive the dynamics of a Differential Wheeled Mobile Robot (DWMR) in the companion paper. The present paper formulates a control system design for trajectory tracking of this class of robots. The method develops a feedback linearization technique for the nonlinear system using dynamic extension algorithm. The effectiveness of the nonlinear controller is illustrated with simulation example

  4. Robust optimal control design using a differential game approach for open-loop linear quadratic descriptor systems

    NARCIS (Netherlands)

    Musthofa, M.W.; Salmah, S.; Engwerda, Jacob; Suparwanto, A.

    This paper studies the robust optimal control problem for descriptor systems. We applied differential game theory to solve the disturbance attenuation problem. The robust control problem was converted into a reduced ordinary zero-sum game. Within a linear quadratic setting, we solved the problem for

  5. Differentiating Approaches to Diabetes Self-Management of Multi-Ethnic Rural Older Adults at the Extremes of Glycemic Control

    Science.gov (United States)

    Brewer-Lowry, Aleshia Nichol; Arcury, Thomas A.; Bell, Ronny A.; Quandt, Sara A.

    2010-01-01

    Purpose of the Study: This study identified approaches to diabetes self-management that differentiate persons with well-controlled from poorly controlled diabetes. Previous research has focused largely on persons participating in self-management interventions. Design and Methods: In-depth qualitative interviews were conducted with 48 adults, drawn…

  6. Differential effects of two virtual reality interventions: distraction versus pain control.

    Science.gov (United States)

    Loreto-Quijada, Desirée; Gutiérrez-Maldonado, José; Nieto, Rubén; Gutiérrez-Martínez, Olga; Ferrer-García, Marta; Saldaña, Carmina; Fusté-Escolano, Adela; Liutsko, Liudmila

    2014-06-01

    There is evidence that virtual reality (VR) pain distraction is effective at improving pain-related outcomes. However, more research is needed to investigate VR environments with other pain-related goals. The main aim of this study was to compare the differential effects of two VR environments on a set of pain-related and cognitive variables during a cold pressor experiment. One of these environments aimed to distract attention away from pain (VRD), whereas the other was designed to enhance pain control (VRC). Participants were 77 psychology students, who were randomly assigned to one of the following three conditions during the cold pressor experiment: (a) VRD, (b) VRC, or (c) Non-VR (control condition). Data were collected regarding both pain-related variables (intensity, tolerance, threshold, time perception, and pain sensitivity range) and cognitive variables (self-efficacy and catastrophizing). Results showed that in comparison with the control condition, the VRC intervention significantly increased pain tolerance, the pain sensitivity range, and the degree of time underestimation. It also increased self-efficacy in tolerating pain and led to a reduction in reported helplessness. The VRD intervention significantly increased the pain threshold and pain tolerance in comparison with the control condition, but it did not affect any of the cognitive variables. Overall, the intervention designed to enhance control seems to have a greater effect on the cognitive variables assessed. Although these results need to be replicated in further studies, the findings suggest that the VRC intervention has considerable potential in terms of increasing self-efficacy and modifying the negative thoughts that commonly accompany pain problems.

  7. Neurophysiological capacity in a working memory task differentiates dependent from nondependent heavy drinkers and controls.

    Science.gov (United States)

    Wesley, Michael J; Lile, Joshua A; Fillmore, Mark T; Porrino, Linda J

    2017-06-01

    Determining the neurobehavioral profiles that differentiate heavy drinkers who are and are not alcohol dependent will inform treatment efforts. Working memory is linked to substance use disorders and can serve as a representation of the demand placed on the neurophysiology associated with cognitive control. Behavior and brain activity (via fMRI) were recorded during an N-Back working memory task in controls (CTRL), nondependent heavy drinkers (A-ND) and dependent heavy drinkers (A-D). Typical and novel step-wise analyses examined profiles of working memory load and increasing task demand, respectively. Performance was significantly decreased in A-D during high working memory load (2-Back), compared to CTRL and A-ND. Analysis of brain activity during high load (0-Back vs. 2- Back) showed greater responses in the dorsal lateral and medial prefrontal cortices of A-D than CTRL, suggesting increased but failed compensation. The step-wise analysis revealed that the transition to Low Demand (0-Back to 1-Back) was associated with robust increases and decreases in cognitive control and default-mode brain regions, respectively, in A-D and A-ND but not CTRL. The transition to High Demand (1-Back to 2-Back) resulted in additional engagement of these networks in A-ND and CTRL, but not A-D. Heavy drinkers engaged working memory neural networks at lower demand than controls. As demand increased, nondependent heavy drinkers maintained control performance but relied on additional neurophysiological resources, and dependent heavy drinkers did not display further resource engagement and had poorer performance. These results support targeting these brain areas for treatment interventions. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Application of CalME incremental-recursive method to the evaluation of the structural condition as asphalt pavements

    International Nuclear Information System (INIS)

    Mateos Moreno, A.; Perez Ayuso, J.; Cadavid Jauregui, B.; Marron Fernandez, J. O.

    2011-01-01

    CalME procedure represents one of the most advanced tools for the design, of flexible pavements world-wide. IT is an incremental-recursive method, which means that pavements service life must be divided into many time intervals where both structural integrity and environmental conditions can be regarded as constants. It also means that the damage calculated at the end of each interval must be considered as initial condition for the next one. The goal of this type of models is the prediction of the evolution of the different distress mechanisms. The advantages of incremental-recursive procedures versus classical analytical design are shown in this paper. Advantages are shown not only in terms of design, but also as a tool in order to support structural evaluation. In particular, the potential of asphalt fatigue model incorporated in CalME is presented. this model is initially calibrated in the laboratory, and it is then re-calibrated based on the actual performance observed from field deflection testing. The model provides a reliable prediction of the future evolution of the damage of the asphalt mixture. Fatigue model validation has been conducted based on the performance from several flexible sections evaluated in CEDEX full-scale pavements test track. (Author) 14 refs.

  9. Functional connectivity in the basal ganglia network differentiates PD patients from controls

    Science.gov (United States)

    Szewczyk-Krolikowski, Konrad; Menke, Ricarda A.L.; Rolinski, Michal; Duff, Eugene; Salimi-Khorshidi, Gholamreza; Filippini, Nicola; Zamboni, Giovanna; Hu, Michele T.M.

    2014-01-01

    Objective: To examine functional connectivity within the basal ganglia network (BGN) in a group of cognitively normal patients with early Parkinson disease (PD) on and off medication compared to age- and sex-matched healthy controls (HC), and to validate the findings in a separate cohort of participants with PD. Methods: Participants were scanned with resting-state fMRI (RS-fMRI) at 3T field strength. Resting-state networks were isolated using independent component analysis. A BGN template was derived from 80 elderly HC participants. BGN maps were compared between 19 patients with PD on and off medication in the discovery group and 19 age- and sex-matched controls to identify a threshold for optimal group separation. The threshold was applied to 13 patients with PD (including 5 drug-naive) in the validation group to establish reproducibility of findings. Results: Participants with PD showed reduced functional connectivity with the BGN in a wide range of areas. Administration of medication significantly improved connectivity. Average BGN connectivity differentiated participants with PD from controls with 100% sensitivity and 89.5% specificity. The connectivity threshold was tested on the validation cohort and achieved 85% accuracy. Conclusions: We demonstrate that resting functional connectivity, measured with MRI using an observer-independent method, is reproducibly reduced in the BGN in cognitively intact patients with PD, and increases upon administration of dopaminergic medication. Our results hold promise for RS-fMRI connectivity as a biomarker in early PD. Classification of evidence: This study provides Class III evidence that average connectivity in the BGN as measured by RS-fMRI distinguishes patients with PD from age- and sex-matched controls. PMID:24920856

  10. Differential expression of proteomics models of colorectal cancer, colorectal benign disease and healthy controls

    Directory of Open Access Journals (Sweden)

    Zhang Shu-Jun

    2010-03-01

    Full Text Available Abstract Background Colorectal cancer (CRC is often diagnosed at a late stage with concomitant poor prognosis. The hypersensitive analytical technique of proteomics can detect molecular changes before the tumor is palpable. The surface-enhanced laser desorption/ionization-time of flight-mass spectra (SELDI-TOF-MS is a newly-developed technique of evaluating protein separation in recent years. The protein chips have established the expression of tumor protein in the serum specimens and become the newly discovered markers for tumor diagnosis. The objective of this study was to find new markers of the diagnosis among groups of CRC, colorectal benign diseases (CBD and healthy controls. The assay of SELDI-TOF-MS with analytical technique of protein-chip bioinformatics was used to detect the expression of protein mass peaks in the sera of patients or controls. One hundred serum samples, including 52 cases of colorectal cancer, 27 cases of colorectal benign disease, and 21 cases of healthy controls, were examined by SELDI-TOF-MS with WCX2 protein-chips. Results The diagnostic models (I, II and III were setup by analyzed the data and sieved markers using Ciphergen - Protein-Chip-Software 5.1. These models were combined with 3 protein mass peaks to discriminate CRC, CBD, and healthy controls. The accuracy, the sensitivity and the particularity of cross verification of these models are all highly over 80%. Conclusions The SELDI-TOF-MS is a useful tool to help diagnose colorectal cancer, especially during the early stage. However, identification of the significantly differentiated proteins needs further study.

  11. ZFX Controls Propagation and Prevents Differentiation of Acute T-Lymphoblastic and Myeloid Leukemia

    Directory of Open Access Journals (Sweden)

    Stuart P. Weisberg

    2014-02-01

    Full Text Available Tumor-propagating cells in acute leukemia maintain a stem/progenitor-like immature phenotype and proliferative capacity. Acute myeloid leukemia (AML and acute T-lymphoblastic leukemia (T-ALL originate from different lineages through distinct oncogenic events such as MLL fusions and Notch signaling, respectively. We found that Zfx, a transcription factor that controls hematopoietic stem cell self-renewal, controls the initiation and maintenance of AML caused by MLL-AF9 fusion and of T-ALL caused by Notch1 activation. In both leukemia types, Zfx prevents differentiation and activates gene sets characteristic of immature cells of the respective lineages. In addition, endogenous Zfx contributes to gene induction and transformation by Myc overexpression in myeloid progenitors. Key Zfx target genes include the mitochondrial enzymes Ptpmt1 and Idh2, whose overexpression partially rescues the propagation of Zfx-deficient AML. These results show that distinct leukemia types maintain their undifferentiated phenotype and self-renewal by exploiting a common stem-cell-related genetic regulator.

  12. An Improved Fuzzy Logic Controller Design for PV Inverters Utilizing Differential Search Optimization

    Directory of Open Access Journals (Sweden)

    Ammar Hussein Mutlag

    2014-01-01

    Full Text Available This paper presents an adaptive fuzzy logic controller (FLC design technique for photovoltaic (PV inverters using differential search algorithm (DSA. This technique avoids the exhaustive traditional trial and error procedure in obtaining membership functions (MFs used in conventional FLCs. This technique is implemented during the inverter design phase by generating adaptive MFs based on the evaluation results of the objective function formulated by the DSA. In this work, the mean square error (MSE of the inverter output voltage is used as an objective function. The DSA optimizes the MFs such that the inverter provides the lowest MSE for output voltage and improves the performance of the PV inverter output in terms of amplitude and frequency. The design procedure and accuracy of the optimum FLC are illustrated and investigated using simulations conducted for a 3 kW three-phase inverter in a MATLAB/Simulink environment. Results show that the proposed controller can successfully obtain the desired output when different linear and nonlinear loads are connected to the system. Furthermore, the inverter has reasonably low steady state error and fast response to reference variation.

  13. Differential mobility analysis of nanoparticles generated by laser vaporization and controlled condensation (LVCC)

    International Nuclear Information System (INIS)

    Abdelsayed, Victor; El-Shall, M. Samy; Seto, Takafumi

    2006-01-01

    Silicon and iron aluminide (FeAl) nanoparticles were synthesized by a laser vaporization controlled condensation (LVCC) method. The particles generated by the laser ablation of solid targets were transported and deposited in the presence of well-defined thermal and electric field in a newly designed flow-type LVCC chamber. The deposition process of nanoparticles was controlled by the balance of the external forces; i.e., gas flow, thermophoretic and electrostatic forces. The size distributions of generated nanoparticles were analyzed using a low-pressure differential mobility analyzer (LP-DMA). The effect of synthesis condition on the size distribution was analyzed by changing the pressure of the carrier gas (20-200 Torr), the temperature gradient in the LVCC chamber (ΔT=0-190 deg. C) and the electric field applied between the LVCC chamber plates (E=0-3000 V/m). It was found that electrostatic field was effective to selectively deposit small size nanoparticles (about 10 nm) with expelling large droplet-like particles

  14. Leak Rate Quantification Method for Gas Pressure Seals with Controlled Pressure Differential

    Science.gov (United States)

    Daniels, Christopher C.; Braun, Minel J.; Oravec, Heather A.; Mather, Janice L.; Taylor, Shawn C.

    2015-01-01

    An enhancement to the pressure decay leak rate method with mass point analysis solved deficiencies in the standard method. By adding a control system, a constant gas pressure differential across the test article was maintained. As a result, the desired pressure condition was met at the onset of the test, and the mass leak rate and measurement uncertainty were computed in real-time. The data acquisition and control system were programmed to automatically stop when specified criteria were met. Typically, the test was stopped when a specified level of measurement uncertainty was attained. Using silicone O-ring test articles, the new method was compared with the standard method that permitted the downstream pressure to be non-constant atmospheric pressure. The two methods recorded comparable leak rates, but the new method recorded leak rates with significantly lower measurement uncertainty, statistical variance, and test duration. Utilizing this new method in leak rate quantification, projects will reduce cost and schedule, improve test results, and ease interpretation between data sets.

  15. Differentiating neural systems mediating the acquisition versus expression of goal-directed and habitual behavioral control

    Science.gov (United States)

    Liljeholm, Mimi; Dunne, Simon; O'Doherty, John P.

    2015-01-01

    Considerable behavioral data indicates that operant actions can become habitual, as evidenced by insensitivity to changes in the action-outcome contingency and in subjective outcome values. Notably, although several studies have investigated the neural substrates of habits, none has clearly differentiated the areas of the human brain that support habit formation from those that implement habitual control. We scanned participants with fMRI as they learned and performed an operant task in which the conditional structure of the environment encouraged either goal-directed encoding of the consequences of actions, or a habit-like mapping of actions to antecedent cues. Participants were also scanned during a subsequent assessment of insensitivity to outcome devaluation. We identified dissociable roles of the cerebellum and ventral striatum, across learning and test performance, in behavioral insensitivity to outcome devaluation. We also show that the inferior parietal lobule – an area previously implicated in several aspects of goal-directed action selection, including the attribution of intent and awareness of agency – predicts sensitivity to outcome devaluation. Finally, we reveal a potential functional homology between the human subgenual cortex and rodent infralimbic cortex in the implementation of habitual control. In summary, our findings suggest a broad systems division, at the cortical and subcortical levels, between brain areas mediating the encoding and expression of action-outcome and stimulus-response associations. PMID:25892332

  16. Identification of Arx targets unveils new candidates for controlling cortical interneuron migration and differentiation

    Directory of Open Access Journals (Sweden)

    Gaelle M Friocourt

    2011-12-01

    Full Text Available Mutations in the homeobox transcription factor ARX have been found to be responsible for a wide spectrum of disorders extending from phenotypes with severe neuronal migration defects, such as lissencephaly, to mild forms of intellectual disabilities without apparent brain abnormalities, but with associated features of dystonia and epilepsy. Arx expression is mainly restricted to populations of GABA-containing neurons. Studies of the effects of ARX loss of function, either in humans or mutant mice, revealed varying defects, suggesting multiple roles of this gene in brain patterning, neuronal proliferation and migration, cell maturation and differentiation, as well as axonal outgrowth and connectivity. However, to date, little is known about how Arx functions as a transcription factor or which genes it binds and regulates. Recently, we combined chromatin immunoprecipitation and mRNA expression with microarray analysis and identified approximately 1000 gene promoters bound by Arx in transfected neuroblastoma N2a cells and mouse embryonic brain. To narrow the analysis of Arx targets to those most likely to control cortical interneuron migration and/or differentiation, we compare here our data to previously published studies searching for genes enriched or down-regulated in cortical interneurons between E13.5 and E15.5. We thus identified 14 Arx-target genes enriched (Cxcr7, Meis1, Ppap2a, Slc12a5, Ets2, Phlda1, Zif268, Igf1, Lmo3, Sema6, Lgi1, Alk, Tgfb3, Napb and 5 genes specifically down-regulated (Hmgn3, Lmo1, Ebf3, Rasgef1b and Slit2 in cortical migrating neurons. In this review, we present these genes and discuss how their possible regulation by Arx may lead to the dysfunction of GABAergic neurons, resulting in mental retardation and epilepsy.

  17. Graphene oxide enrichment of collagen membranes improves DPSCs differentiation and controls inflammation occurrence.

    Science.gov (United States)

    Radunovic, Milena; De Colli, Marianna; De Marco, Patrizia; Di Nisio, Chiara; Fontana, Antonella; Piattelli, Adriano; Cataldi, Amelia; Zara, Susi

    2017-08-01

    Collagen membranes are used in oral surgery for bone defects treatment acting as a barrier that does not allow the invasion of soft tissue into the growing bone. To improve biocompatibility collagen membranes were coated with graphene oxide (GO), a graphene derivative. The aim of this study was to investigate the biocompatibility of GO coated collagen membranes on human dental pulp stem cells (DPSCs) focusing on biomaterial cytotoxicity, ability to promote DPSCs differentiation process and to control inflammation event induction. DPSCs were cultured on uncoated membranes and on both 2 and 10 μg mL -1 GO coated membranes up to 28 days. Alamar blue and LDH cytotocicity assay, PGE2 ELISA assay, real time RT-PCR for RUNX2, BMP2, SP7, TNFα and COX2 genes expression were performed. Proliferation is higher on GO coated membranes at days 14 and 28. LDH assay evidences no cytotoxicity. BMP2 and RUNX2 expression is higher on coated membranes, BMP2 at early and RUNX2 and SP7 at late experimental times. PGE2 levels are lower on GO coated membranes at days 14 and 28, both TNFα and COX2 expression is significantly decreased when GO is applied. GO coated membranes are not toxic for DPSCs, induce a faster DPSCs differentiation into odontoblasts/osteoblasts and may represent good alternative to conventional membranes thus ensuring more efficient bone formation and improving the clinical performance. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2312-2320, 2017. © 2017 Wiley Periodicals, Inc.

  18. No differential attrition was found in randomized controlled trials published in general medical journals: a meta-analysis.

    Science.gov (United States)

    Crutzen, Rik; Viechtbauer, Wolfgang; Kotz, Daniel; Spigt, Mark

    2013-09-01

    Differential attrition is regarded as a major threat to the internal validity of a randomized controlled trial (RCT). This study identifies the degree of differential attrition in RCTs covering a broad spectrum of clinical areas and factors that are related to this. A PubMed search was conducted to obtain a random sample of 100 RCTs published between 2008 and 2010 in journals from the ISI Web of Knowledge(SM) category of medicine, general and internal. Eligibility criteria for selecting studies were primary publications of two-arm parallel randomized clinical trials, containing human participants and one or multiple follow-up measurements whose availability depended on the patients' willingness to participate. A significant amount of differential attrition was observed in 8% of the trials. The average differential attrition rate was 0.99 (95% confidence interval: 0.97-1.01), indicating no general difference in attrition rates between intervention and control groups. Moreover, no indication of heterogeneity was found, suggesting that the occurrence of differential attrition in the published literature is mostly a chance finding, unrelated to any particular design factors. Differential attrition did not generally occur in RCTs covering a broad spectrum of clinical areas within general and internal medicine. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Controllability of nonlocal second-order impulsive neutral stochastic functional integro-differential equations with delay and Poisson jumps

    Directory of Open Access Journals (Sweden)

    Diem Dang Huan

    2015-12-01

    Full Text Available The current paper is concerned with the controllability of nonlocal second-order impulsive neutral stochastic functional integro-differential equations with infinite delay and Poisson jumps in Hilbert spaces. Using the theory of a strongly continuous cosine family of bounded linear operators, stochastic analysis theory and with the help of the Banach fixed point theorem, we derive a new set of sufficient conditions for the controllability of nonlocal second-order impulsive neutral stochastic functional integro-differential equations with infinite delay and Poisson jumps. Finally, an application to the stochastic nonlinear wave equation with infinite delay and Poisson jumps is given.

  20. The influence of ship movements on the energy expenditure of fishermen. A study during a North Sea Voyage in calm weather

    DEFF Research Database (Denmark)

    Breidahl, Tomas; Christensen, Michael; Johansen, Jens Peter

    2015-01-01

    in the North Sea off the coast of Bergen. The data were analysed by linear regression. results: The exposure monitored in calm weather conditions was small for all meas- urements of heeling and pitch being less than 10o.for both vessels. However, the fish- ermen’s energy expenditure was influenced...... by these minor sea motions. Trends were seen in the individual graphs with increasing energy expenditure at higher exposures. Conclusion: Our data suggests that even the heel and pitch in calm weather have an impact on the fishermen by increasing their energy consumption. This study has demonstrated...

  1. Randomized double-blind trial of prophylactic topical Evozac® Calming Skin Spray for gefitinib-associated acne-like eruption

    Directory of Open Access Journals (Sweden)

    Wang Y

    2014-07-01

    Full Text Available Yalan Wang,* Yunpeng Yang,* Jinxia Xu, Juan Yu, Xia Liu, Ruizhen Gao, Li Zhang State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Sun Yat-sen University Cancer Center, Guangzhou, Guangdong, People's Republic of China *These authors contributed equally to this work Background: "Gefitinib" is a first-generation epidermal growth factor receptor tyrosine-kinase inhibitor. More than half of patients receiving gefitinib develop acne-like eruption. Evozac® Calming Skin Spray (Evaux Laboratoires, Évaux-les-Bains, France is made of Évaux thermal spring water and commonly used for the treatment of dermatological toxicities caused by anti- epidermal growth factor receptor therapy. The aim of the study reported here was to test the effect of Evozac Calming Skin Spray on the prevention of rash in patients receiving gefitinib. Methods: Non-small-cell lung cancer patients preparing to initiate gefitinib therapy were randomly assigned to apply Evozac Calming Skin Spray or physiological saline to the face three times a day. The treatment was started on the same day as initiation of gefitinib therapy and continued for 4 weeks. Results: A total of 51 patients in the Evozac Calming Skin Spray group and 50 patients in the physiological saline group completed the study per the protocol. The number of facial lesions peaked at the end of 3 weeks in both groups. There were significantly fewer lesions in the Evozac Calming Skin Spray group than in the physiological saline group at the end of 1 week (0.25 versus [vs] 1.10, P=0.031 and 3 weeks (6.67 vs 12.26, P=0.022. Patients from the Evozac Calming Skin Spray group also developed fewer facial lesions at the end of 2 weeks and 4 weeks, however, the difference was not statistically significant. At the end of 4 weeks, fewer patients from the Evozac Calming Skin Spray group developed rash of grade 2 or greater severity (17.6% vs 36.0%, P=0.037, or experienced rash

  2. Differential Control Efficacies of Vitamin Treatments against Bacterial Wilt and Grey Mould Diseases in Tomato Plants

    Directory of Open Access Journals (Sweden)

    Jeum Kyu Hong

    2016-10-01

    Full Text Available Bacterial wilt and grey mould in tomato plants are economically destructive bacterial and fungal diseases caused by Ralstonia solanacearum and Botrytis cinerea, respectively. Various approaches including chemical and biological controls have been attempted to arrest the tomato diseases so far. In this study, in vitro growths of bacterial R. solanacearum and fungal B. cinerea were evaluated using four different vitamins including thiamine (vitamin B1, niacin (vitamin B3, pyridoxine (vitamin B6, and menadione (vitamin K3. In planta efficacies of the four vitamin treatments on tomato protection against both diseases were also demonstrated. All four vitamins showed different in vitro antibacterial activities against R. solanacearum in dose-dependent manners. However, treatment with 2 mM thiamine was only effective in reducing bacterial wilt of detached tomato leaves without phytotoxicity under lower disease pressure (10⁶ colony-forming unit [cfu]/ml. Treatment with the vitamins also differentially reduced in vitro conidial germination and mycelial growth of B. cinerea. The four vitamins slightly reduced the conidial germination, and thiamine, pyridoxine and menadione inhibited the mycelial growth of B. cinerea. Menadione began to drastically suppress the conidial germination and mycelial growth by 5 and 0.5 mM, respectively. Grey mould symptoms on the inoculated tomato leaves were significantly reduced by pyridoxine and menadione pretreatments one day prior to the fungal challenge inoculation. These findings suggest that disease-specific vitamin treatment will be integrated for eco-friendly management of tomato bacterial wilt and grey mould.

  3. Differential Control Efficacies of Vitamin Treatments against Bacterial Wilt and Grey Mould Diseases in Tomato Plants.

    Science.gov (United States)

    Hong, Jeum Kyu; Kim, Hyeon Ji; Jung, Heesoo; Yang, Hye Ji; Kim, Do Hoon; Sung, Chang Hyun; Park, Chang-Jin; Chang, Seog Won

    2016-10-01

    Bacterial wilt and grey mould in tomato plants are economically destructive bacterial and fungal diseases caused by Ralstonia solanacearum and Botrytis cinerea , respectively. Various approaches including chemical and biological controls have been attempted to arrest the tomato diseases so far. In this study, in vitro growths of bacterial R. solanacearum and fungal B. cinerea were evaluated using four different vitamins including thiamine (vitamin B1), niacin (vitamin B3), pyridoxine (vitamin B6), and menadione (vitamin K3). In planta efficacies of the four vitamin treatments on tomato protection against both diseases were also demonstrated. All four vitamins showed different in vitro antibacterial activities against R. solanacearum in dose-dependent manners. However, treatment with 2 mM thiamine was only effective in reducing bacterial wilt of detached tomato leaves without phytotoxicity under lower disease pressure (10 6 colony-forming unit [cfu]/ml). Treatment with the vitamins also differentially reduced in vitro conidial germination and mycelial growth of B. cinerea . The four vitamins slightly reduced the conidial germination, and thiamine, pyridoxine and menadione inhibited the mycelial growth of B. cinerea . Menadione began to drastically suppress the conidial germination and mycelial growth by 5 and 0.5 mM, respectively. Grey mould symptoms on the inoculated tomato leaves were significantly reduced by pyridoxine and menadione pretreatments one day prior to the fungal challenge inoculation. These findings suggest that disease-specific vitamin treatment will be integrated for eco-friendly management of tomato bacterial wilt and grey mould.

  4. D-Serine and Glycine Differentially Control Neurotransmission during Visual Cortex Critical Period.

    Directory of Open Access Journals (Sweden)

    Claire N J Meunier

    Full Text Available N-methyl-D-aspartate receptors (NMDARs play a central role in synaptic plasticity. Their activation requires the binding of both glutamate and d-serine or glycine as co-agonist. The prevalence of either co-agonist on NMDA-receptor function differs between brain regions and remains undetermined in the visual cortex (VC at the critical period of postnatal development. Here, we therefore investigated the regulatory role that d-serine and/or glycine may exert on NMDARs function and on synaptic plasticity in the rat VC layer 5 pyramidal neurons of young rats. Using selective enzymatic depletion of d-serine or glycine, we demonstrate that d-serine and not glycine is the endogenous co-agonist of synaptic NMDARs required for the induction and expression of Long Term Potentiation (LTP at both excitatory and inhibitory synapses. Glycine on the other hand is not involved in synaptic efficacy per se but regulates excitatory and inhibitory neurotransmission by activating strychnine-sensitive glycine receptors, then producing a shunting inhibition that controls neuronal gain and results in a depression of synaptic inputs at the somatic level after dendritic integration. In conclusion, we describe for the first time that in the VC both D-serine and glycine differentially regulate somatic depolarization through the activation of distinct synaptic and extrasynaptic receptors.

  5. LOOP- SIMULATION OF THE AUTOMATIC FREQUENCY CONTROL SUBSYSTEM OF A DIFFERENTIAL MINIMUM SHIFT KEYING RECEIVER

    Science.gov (United States)

    Davarian, F.

    1994-01-01

    The LOOP computer program was written to simulate the Automatic Frequency Control (AFC) subsystem of a Differential Minimum Shift Keying (DMSK) receiver with a bit rate of 2400 baud. The AFC simulated by LOOP is a first order loop configuration with a first order R-C filter. NASA has been investigating the concept of mobile communications based on low-cost, low-power terminals linked via geostationary satellites. Studies have indicated that low bit rate transmission is suitable for this application, particularly from the frequency and power conservation point of view. A bit rate of 2400 BPS is attractive due to its applicability to the linear predictive coding of speech. Input to LOOP includes the following: 1) the initial frequency error; 2) the double-sided loop noise bandwidth; 3) the filter time constants; 4) the amount of intersymbol interference; and 5) the bit energy to noise spectral density. LOOP output includes: 1) the bit number and the frequency error of that bit; 2) the computed mean of the frequency error; and 3) the standard deviation of the frequency error. LOOP is written in MS SuperSoft FORTRAN 77 for interactive execution and has been implemented on an IBM PC operating under PC DOS with a memory requirement of approximately 40K of 8 bit bytes. This program was developed in 1986.

  6. Glucose-ABL1-TOR Signaling Modulates Cell Cycle Tuning to Control Terminal Appressorial Cell Differentiation.

    Science.gov (United States)

    Marroquin-Guzman, Margarita; Sun, Guangchao; Wilson, Richard A

    2017-01-01

    The conserved target of rapamycin (TOR) pathway integrates growth and development with available nutrients, but how cellular glucose controls TOR function and signaling is poorly understood. Here, we provide functional evidence from the devastating rice blast fungus Magnaporthe oryzae that glucose can mediate TOR activity via the product of a novel carbon-responsive gene, ABL1, in order to tune cell cycle progression during infection-related development. Under nutrient-free conditions, wild type (WT) M. oryzae strains form terminal plant-infecting cells (appressoria) at the tips of germ tubes emerging from three-celled spores (conidia). WT appressorial development is accompanied by one round of mitosis followed by autophagic cell death of the conidium. In contrast, Δabl1 mutant strains undergo multiple rounds of accelerated mitosis in elongated germ tubes, produce few appressoria, and are abolished for autophagy. Treating WT spores with glucose or 2-deoxyglucose phenocopied Δabl1. Inactivating TOR in Δabl1 mutants or glucose-treated WT strains restored appressorium formation by promoting mitotic arrest at G1/G0 via an appressorium- and autophagy-inducing cell cycle delay at G2/M. Collectively, this work uncovers a novel glucose-ABL1-TOR signaling axis and shows it engages two metabolic checkpoints in order to modulate cell cycle tuning and mediate terminal appressorial cell differentiation. We thus provide new molecular insights into TOR regulation and cell development in response to glucose.

  7. Differential application of lambda-cyhalothrin to control the sandfly Lutzomyia longipalpis.

    Science.gov (United States)

    Kelly, D W; Mustafa, Z; Dye, C

    1997-01-01

    To study the impact of residual pyrethroid insecticide on the abundance and distribution of peridomestic Lutzomyia longipalpis, the sandfly vector of visceral leishmaniasis in Brazil, lambda-cyhalothrin was applied at 20 mg a.i.m-2 in the following interventions: (i) spraying of all animal pens in a village (blanket coverage); (ii) treatment of a subset of animal pens, either by spraying, or by installation of insecticide-impregnated 1 m2 cotton sheets as 'targets' (focal coverage). By sampling with CDC light traps, and using a novel analytical approach, we detected a 90% reduction in Lu.longipalpis abundance in sprayed sheds of the focal intervention. However, there was no discernible effect on the abundance of other phlebotomines trapped in sheds, or on the abundance of Lu.longipalpis in untreated dining-huts and houses. This differential impact on Lu.longipalpis abundance is explained in terms of the disruption of male pheromone production. Treated targets were approximately half as effective as residual spraying in reducing the abundance of Lu.longipalpis in sheds. Following blanket intervention, the abundance of Lu.longipalpis in traps fell by only 45% (not significant): catches at untreated dining-huts actually increased, possibly because the blanket coverage diverted Lu.longipalpis away from major aggregation sites at animal pens. It is recommended that care be taken during vector control programmes to ensure that all potential aggregation sites are treated. The possible consequences of leaving some sites untreated include poor control of peridomestic sandfly abundance and an increase in the biting rate on dogs and humans.

  8. Differential Effect of Race, Education, Gender, and Language Discrimination on Glycemic Control in Adults with Type 2 Diabetes

    OpenAIRE

    Brice Reynolds, D.; Walker, Rebekah J.; Campbell, Jennifer A.; Egede, Leonard E.

    2015-01-01

    Background: Discrimination has been linked to negative health outcomes, but little research has investigated different types of discrimination to determine if some have a greater impact on outcomes. We examined the differential effect of discrimination based on race, level of education, gender, and language on glycemic control in adults with type 2 diabetes.

  9. Impact of a Differential Learning Approach on Practical Exam Performance: A Controlled Study in a Preclinical Dental Course.

    Science.gov (United States)

    Pabel, Sven-Olav; Pabel, Anne-Kathrin; Schmickler, Jan; Schulz, Xenia; Wiegand, Annette

    2017-09-01

    The aim of this study was to evaluate if differential learning in a preclinical dental course impacted the performance of dental students in a practical exam (preparation of a gold partial crown) immediately after the training session and 20 weeks later compared to conventional learning. This controlled study was performed in a preclinical course in operative dentistry at a dental school in Germany. Third-year students were trained in preparing gold partial crowns by using either the conventional learning (n=41) or the differential learning approach (n=32). The differential learning approach consisted of 20 movement exercises with a continuous change of movement execution during the learning session, while the conventional learning approach was mainly based on repetition, a methodological series of exercises, and correction of preparations during the training phase. Practical exams were performed immediately after the training session (T1) and 20 weeks later (T2, retention test). Preparations were rated by four independent and blinded examiners. At T1, no significant difference between the performance (exam passed) of the two groups was detected (conventional learning: 54.3%, differential learning: 68.0%). At T2, significantly more students passed the exam when trained by the differential learning approach (68.8%) than by the conventional learning approach (18.9%). Interrater reliability was moderate (Kappa: 0.57, T1) or substantial (Kappa: 0.67, T2), respectively. These results suggest that a differential learning approach can increase the manual skills of dental students.

  10. Reverse engineering life: physical and chemical mimetics for controlled stem cell differentiation into cardiomyocytes.

    Science.gov (United States)

    Skuse, Gary R; Lamkin-Kennard, Kathleen A

    2013-01-01

    Our ability to manipulate stem cells in order to induce differentiation along a desired developmental pathway has improved immeasurably in recent years. That is in part because we have a better understanding of the intracellular and extracellular signals that regulate differentiation. However, there has also been a realization that stem cell differentiation is not regulated only by chemical signals but also by the physical milieu in which a particular stem cell exists. In this regard we are challenged to mimic both chemical and physical environments. Herein we describe a method to induce stem cell differentiation into cardiomyocytes using a combination of chemical and physical cues. This method can be applied to produce differentiated cells for research and potentially for cell-based therapy of cardiomyopathies.

  11. Sample size calculation while controlling false discovery rate for differential expression analysis with RNA-sequencing experiments.

    Science.gov (United States)

    Bi, Ran; Liu, Peng

    2016-03-31

    RNA-Sequencing (RNA-seq) experiments have been popularly applied to transcriptome studies in recent years. Such experiments are still relatively costly. As a result, RNA-seq experiments often employ a small number of replicates. Power analysis and sample size calculation are challenging in the context of differential expression analysis with RNA-seq data. One challenge is that there are no closed-form formulae to calculate power for the popularly applied tests for differential expression analysis. In addition, false discovery rate (FDR), instead of family-wise type I error rate, is controlled for the multiple testing error in RNA-seq data analysis. So far, there are very few proposals on sample size calculation for RNA-seq experiments. In this paper, we propose a procedure for sample size calculation while controlling FDR for RNA-seq experimental design. Our procedure is based on the weighted linear model analysis facilitated by the voom method which has been shown to have competitive performance in terms of power and FDR control for RNA-seq differential expression analysis. We derive a method that approximates the average power across the differentially expressed genes, and then calculate the sample size to achieve a desired average power while controlling FDR. Simulation results demonstrate that the actual power of several popularly applied tests for differential expression is achieved and is close to the desired power for RNA-seq data with sample size calculated based on our method. Our proposed method provides an efficient algorithm to calculate sample size while controlling FDR for RNA-seq experimental design. We also provide an R package ssizeRNA that implements our proposed method and can be downloaded from the Comprehensive R Archive Network ( http://cran.r-project.org ).

  12. Aging and insulin signaling differentially control normal and tumorous germline stem cells.

    Science.gov (United States)

    Kao, Shih-Han; Tseng, Chen-Yuan; Wan, Chih-Ling; Su, Yu-Han; Hsieh, Chang-Che; Pi, Haiwei; Hsu, Hwei-Jan

    2015-02-01

    Aging influences stem cells, but the processes involved remain unclear. Insulin signaling, which controls cellular nutrient sensing and organismal aging, regulates the G2 phase of Drosophila female germ line stem cell (GSC) division cycle in response to diet; furthermore, this signaling pathway is attenuated with age. The role of insulin signaling in GSCs as organisms age, however, is also unclear. Here, we report that aging results in the accumulation of tumorous GSCs, accompanied by a decline in GSC number and proliferation rate. Intriguingly, GSC loss with age is hastened by either accelerating (through eliminating expression of Myt1, a cell cycle inhibitory regulator) or delaying (through mutation of insulin receptor (dinR) GSC division, implying that disrupted cell cycle progression and insulin signaling contribute to age-dependent GSC loss. As flies age, DNA damage accumulates in GSCs, and the S phase of the GSC cell cycle is prolonged. In addition, GSC tumors (which escape the normal stem cell regulatory microenvironment, known as the niche) still respond to aging in a similar manner to normal GSCs, suggesting that niche signals are not required for GSCs to sense or respond to aging. Finally, we show that GSCs from mated and unmated females behave similarly, indicating that female GSC-male communication does not affect GSCs with age. Our results indicate the differential effects of aging and diet mediated by insulin signaling on the stem cell division cycle, highlight the complexity of the regulation of stem cell aging, and describe a link between ovarian cancer and aging. © 2014 The Authors. Aging Cell published by the Anatomical Society and John Wiley & Sons Ltd.

  13. Temporomandibular disorders are differentially associated with headache diagnoses: a controlled study.

    Science.gov (United States)

    Gonçalves, Daniela A G; Camparis, Cinara M; Speciali, José G; Franco, Ana L; Castanharo, Sabrina M; Bigal, Marcelo E

    2011-09-01

    Temporomandibular disorders (TMDs) are considered to be comorbid with headaches. Earlier population studies have suggested that TMD may also be a risk factor for migraine progression. If that is true, TMD should be associated with specific headache syndromes (eg, migraine and chronic migraine), but not with headaches overall. Accordingly, our aim was to explore the relationship between TMD subtypes and severity with primary headaches in a controlled clinical study. The sample consisted of 300 individuals. TMDs were assessed using the Research Diagnostic Criteria for TMD, and primary headache was classified according to International Classification for Headache Disorders-2. Univariate and multivariate models assessed headache diagnoses and frequency as a function of the parameters of TMD. Relative to those without TMD, individuals with myofascial TMD were significantly more likely to have chronic daily headaches (CDHs) [relative risk (RR)=7.8; 95% confidence interval (CI), 3.1-19.6], migraine (RR=4.4; 95% CI, 1.7-11.7), and episodic tension-type headache (RR=4.4; 95% CI, 1.5-12.6). Grade of TMD pain was associated with increased odds of CDH (Pheadache (Pheadache frequency. In multivariate analyses, TMD was associated with migraine and CDH (P=0.001). Painful TMD (P=0.0034) and grade of TMD pain (Pheadache frequency. TMD, TMD subtypes, and TMD severity are independently associated with specific headache syndromes and with headache frequency. This differential association suggests that the presence of central facilitation of nociceptive inputs may be of importance, as positive association was observed only when muscular TMD pain was involved.

  14. Spectral control of an alexandrite laser for an airborne water-vapor differential absorption lidar system

    Science.gov (United States)

    Ponsardin, Patrick; Grossmann, Benoist E.; Browell, Edward V.

    1994-01-01

    A narrow-linewidth pulsed alexandrite laser has been greatly modified for improved spectral stability in an aircraft environment, and its operation has been evaluated in the laboratory for making water-vapor differential absorption lidar measurements. An alignment technique is described to achieve the optimum free spectral range ratio for the two etalons inserted in the alexandrite laser cavity, and the sensitivity of this ratio is analyzed. This technique drastically decreases the occurrence of mode hopping, which is commonly observed in a tunable, two-intracavity-etalon laser system. High spectral purity (greater than 99.85%) at 730 nm is demonstrated by the use of a water-vapor absorption line as a notch filter. The effective cross sections of 760-nm oxygen and 730-nm water-vapor absorption lines are measured at different pressures by using this laser, which has a finite linewidth of 0.02 cm(exp -1) (FWHM). It is found that for water-vapor absorption linewidths greater than 0.04 cm(exp -1) (HWHM), or for altitudes below 10 km, the laser line can be considered monochromatic because the measured effective absorption cross section is within 1% of the calculated monochromatic cross section. An analysis of the environmental sensitivity of the two intracavity etalons is presented, and a closed-loop computer control for active stabilization of the two intracavity etalons in the alexandrite laser is described. Using a water-vapor absorption line as a wavelength reference, we measure a long-term frequency drift (approximately 1.5 h) of less than 0.7 pm in the laboratory.

  15. Physicochemical Control of Adult Stem Cell Differentiation: Shedding Light on Potential Molecular Mechanisms

    Science.gov (United States)

    2010-01-01

    stem - cell -based biomedical and therapeutic applications, including tissue engineering, requires an understanding of the cell-cell and cell-environment interactions. To this end, recent efforts have been focused on the manipulation of adult stem cell differentiation using inductive soluble factors, designing suitable mechanical environments, and applying noninvasive physical forces. Although each of these different approaches has been successfully applied to regulate stem cell differentiation, it would be of great interest and

  16. Extrinsic and intrinsic factors controlling spermatogonial stem cell self-renewal and differentiation

    OpenAIRE

    Mei, Xing-Xing; Wang, Jian; Wu, Ji

    2015-01-01

    Spermatogonial stem cells (SSCs), the stem cells responsible for male fertility, are one of a small number of cells with the abilities of both self-renewal and generation of large numbers of haploid cells. Technology improvements, most importantly, transplantation assays and in vitro culture systems have greatly expanded our understanding of SSC self-renewal and differentiation. Many important molecules crucial for the balance between self-renewal and differentiation have been recently identi...

  17. Bias due to differential participation in case-control studies and review of available approaches for adjustment.

    Science.gov (United States)

    Aigner, Annette; Grittner, Ulrike; Becher, Heiko

    2018-01-01

    Low response rates in epidemiologic research potentially lead to the recruitment of a non-representative sample of controls in case-control studies. Problems in the unbiased estimation of odds ratios arise when characteristics causing the probability of participation are associated with exposure and outcome. This is a specific setting of selection bias and a realistic hazard in many case-control studies. This paper formally describes the problem and shows its potential extent, reviews existing approaches for bias adjustment applicable under certain conditions, compares and applies them. We focus on two scenarios: a characteristic C causing differential participation of controls is linked to the outcome through its association with risk factor E (scenario I), and C is additionally a genuine risk factor itself (scenario II). We further assume external data sources are available which provide an unbiased estimate of C in the underlying population. Given these scenarios, we (i) review available approaches and their performance in the setting of bias due to differential participation; (ii) describe two existing approaches to correct for the bias in both scenarios in more detail; (iii) present the magnitude of the resulting bias by simulation if the selection of a non-representative sample is ignored; and (iv) demonstrate the approaches' application via data from a case-control study on stroke. The bias of the effect measure for variable E in scenario I and C in scenario II can be large and should therefore be adjusted for in any analysis. It is positively associated with the difference in response rates between groups of the characteristic causing differential participation, and inversely associated with the total response rate in the controls. Adjustment in a standard logistic regression framework is possible in both scenarios if the population distribution of the characteristic causing differential participation is known or can be approximated well.

  18. Numerical analysis for trajectory controllability of a coupled multi-order fractional delay differential system via the shifted Jacobi method

    Science.gov (United States)

    Priya, B. Ganesh; Muthukumar, P.

    2018-02-01

    This paper deals with the trajectory controllability for a class of multi-order fractional linear systems subject to a constant delay in state vector. The solution for the coupled fractional delay differential equation is established by the Mittag-Leffler function. The necessary and sufficient condition for the trajectory controllability is formulated and proved by the generalized Gronwall's inequality. The approximate trajectory for the proposed system is obtained through the shifted Jacobi operational matrix method. The numerical simulation of the approximate solution shows the theoretical results. Finally, some remarks and comments on the existing results of constrained controllability for the fractional dynamical system are also presented.

  19. Gender-Differentiated Parenting Revisited: Meta-Analysis Reveals Very Few Differences in Parental Control of Boys and Girls

    Science.gov (United States)

    Endendijk, Joyce J.; Groeneveld, Marleen G.; Bakermans-Kranenburg, Marian J.; Mesman, Judi

    2016-01-01

    Although various theories describe mechanisms leading to differential parenting of boys and girls, there is no consensus about the extent to which parents do treat their sons and daughters differently. The last meta-analyses on the subject were conducted more than fifteen years ago, and changes in gender-specific child rearing in the past decade are quite plausible. In the current set of meta-analyses, based on 126 observational studies (15,034 families), we examined mothers’ and fathers’ differential use of autonomy-supportive and controlling strategies with boys and girls, and the role of moderators related to the decade in which the study was conducted, the observational context, and sample characteristics. Databases of Web of Science, ERIC, PsychInfo, Online Contents, Picarta, and Proquest were searched for studies examining differences in observed parental control of boys and girls between the ages of 0 and 18 years. Few differences were found in parents’ use of control with boys and girls. Parents were slightly more controlling with boys than with girls, but the effect size was negligible (d = 0.08). The effect was larger, but still small, in normative groups and in samples with younger children. No overall effect for gender-differentiated autonomy-supportive strategies was found (d = 0.03). A significant effect of time emerged: studies published in the 1970s and 1980s reported more autonomy-supportive strategies with boys than toward girls, but from 1990 onwards parents showed somewhat more autonomy-supportive strategies with girls than toward boys. Taking into account parents’ gender stereotypes might uncover subgroups of families where gender-differentiated control is salient, but based on our systematic review of the currently available large data base we conclude that in general the differences between parenting of boys versus girls are minimal. PMID:27416099

  20. Gender-Differentiated Parenting Revisited: Meta-Analysis Reveals Very Few Differences in Parental Control of Boys and Girls.

    Directory of Open Access Journals (Sweden)

    Joyce J Endendijk

    Full Text Available Although various theories describe mechanisms leading to differential parenting of boys and girls, there is no consensus about the extent to which parents do treat their sons and daughters differently. The last meta-analyses on the subject were conducted more than fifteen years ago, and changes in gender-specific child rearing in the past decade are quite plausible. In the current set of meta-analyses, based on 126 observational studies (15,034 families, we examined mothers' and fathers' differential use of autonomy-supportive and controlling strategies with boys and girls, and the role of moderators related to the decade in which the study was conducted, the observational context, and sample characteristics. Databases of Web of Science, ERIC, PsychInfo, Online Contents, Picarta, and Proquest were searched for studies examining differences in observed parental control of boys and girls between the ages of 0 and 18 years. Few differences were found in parents' use of control with boys and girls. Parents were slightly more controlling with boys than with girls, but the effect size was negligible (d = 0.08. The effect was larger, but still small, in normative groups and in samples with younger children. No overall effect for gender-differentiated autonomy-supportive strategies was found (d = 0.03. A significant effect of time emerged: studies published in the 1970s and 1980s reported more autonomy-supportive strategies with boys than toward girls, but from 1990 onwards parents showed somewhat more autonomy-supportive strategies with girls than toward boys. Taking into account parents' gender stereotypes might uncover subgroups of families where gender-differentiated control is salient, but based on our systematic review of the currently available large data base we conclude that in general the differences between parenting of boys versus girls are minimal.

  1. Gender-Differentiated Parenting Revisited: Meta-Analysis Reveals Very Few Differences in Parental Control of Boys and Girls.

    Science.gov (United States)

    Endendijk, Joyce J; Groeneveld, Marleen G; Bakermans-Kranenburg, Marian J; Mesman, Judi

    2016-01-01

    Although various theories describe mechanisms leading to differential parenting of boys and girls, there is no consensus about the extent to which parents do treat their sons and daughters differently. The last meta-analyses on the subject were conducted more than fifteen years ago, and changes in gender-specific child rearing in the past decade are quite plausible. In the current set of meta-analyses, based on 126 observational studies (15,034 families), we examined mothers' and fathers' differential use of autonomy-supportive and controlling strategies with boys and girls, and the role of moderators related to the decade in which the study was conducted, the observational context, and sample characteristics. Databases of Web of Science, ERIC, PsychInfo, Online Contents, Picarta, and Proquest were searched for studies examining differences in observed parental control of boys and girls between the ages of 0 and 18 years. Few differences were found in parents' use of control with boys and girls. Parents were slightly more controlling with boys than with girls, but the effect size was negligible (d = 0.08). The effect was larger, but still small, in normative groups and in samples with younger children. No overall effect for gender-differentiated autonomy-supportive strategies was found (d = 0.03). A significant effect of time emerged: studies published in the 1970s and 1980s reported more autonomy-supportive strategies with boys than toward girls, but from 1990 onwards parents showed somewhat more autonomy-supportive strategies with girls than toward boys. Taking into account parents' gender stereotypes might uncover subgroups of families where gender-differentiated control is salient, but based on our systematic review of the currently available large data base we conclude that in general the differences between parenting of boys versus girls are minimal.

  2. Skeletal (stromal) stem cells: an update on intracellular signaling pathways controlling osteoblast differentiation.

    Science.gov (United States)

    Abdallah, Basem M; Jafari, Abbas; Zaher, Walid; Qiu, Weimin; Kassem, Moustapha

    2015-01-01

    Skeletal (marrow stromal) stem cells (BMSCs) are a group of multipotent cells that reside in the bone marrow stroma and can differentiate into osteoblasts, chondrocytes and adipocytes. Studying signaling pathways that regulate BMSC differentiation into osteoblastic cells is a strategy for identifying druggable targets for enhancing bone formation. This review will discuss the functions and the molecular mechanisms of action on osteoblast differentiation and bone formation; of a number of recently identified regulatory molecules: the non-canonical Notch signaling molecule Delta-like 1/preadipocyte factor 1 (Dlk1/Pref-1), the Wnt co-receptor Lrp5 and intracellular kinases. This article is part of a Special Issue entitled: Stem Cells and Bone. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Mdm2 controls CREB-dependent transactivation and initiation of adipocyte differentiation

    DEFF Research Database (Denmark)

    Hallenborg, Philip; Feddersen, Søren; Francoz, S.

    2012-01-01

    The role of the E3 ubiquitin ligase murine double minute 2 (Mdm2) in regulating the stability of the p53 tumor suppressor is well documented. By contrast, relatively little is known about p53-independent activities of Mdm2 and the role of Mdm2 in cellular differentiation. Here we report a novel r...... in the myoblast cell line C2C12, it is conceivable that Mdm2 acts as a switch in cell fate determination. Cell Death and Differentiation (2012) 19, 1381-1389; doi:10.1038/cdd.2012.15; published online 2 March 2012...

  4. Cdc42 controls progenitor cell differentiation and beta-catenin turnover in skin

    DEFF Research Database (Denmark)

    Wu, Xunwei; Quondamatteo, Fabio; Lefever, Tine

    2006-01-01

    for differentiation of skin progenitor cells into HF lineage and that it regulates the turnover of beta-catenin. In the absence of Cdc42, degradation of beta-catenin was increased corresponding to a decreased phosphorylation of GSK3beta at Ser 9 and an increased phosphorylation of axin, which is known to be required...... for binding of beta-catenin to the degradation machinery. Cdc42-mediated regulation of beta-catenin turnover was completely dependent on PKCzeta, which associated with Cdc42, Par6, and Par3. These data suggest that Cdc42 regulation of beta-catenin turnover is important for terminal differentiation of HF...

  5. Existence and controllability results for damped second order impulsive functional differential systems with state-dependent delay

    Directory of Open Access Journals (Sweden)

    M. Mallika Arjunan

    2014-01-01

    Full Text Available In this paper, we investigate the existence and controllability of mild solutions for a damped second order impulsive functional differential equation with state-dependent delay in Banach spaces. The results are obtained by using Sadovskii's fixed point theorem combined with the theories of a strongly continuous cosine family of bounded linear operators. Finally, an example is provided to illustrate the main results.

  6. CFORM- LINEAR CONTROL SYSTEM DESIGN AND ANALYSIS: CLOSED FORM SOLUTION AND TRANSIENT RESPONSE OF THE LINEAR DIFFERENTIAL EQUATION

    Science.gov (United States)

    Jamison, J. W.

    1994-01-01

    CFORM was developed by the Kennedy Space Center Robotics Lab to assist in linear control system design and analysis using closed form and transient response mechanisms. The program computes the closed form solution and transient response of a linear (constant coefficient) differential equation. CFORM allows a choice of three input functions: the Unit Step (a unit change in displacement); the Ramp function (step velocity); and the Parabolic function (step acceleration). It is only accurate in cases where the differential equation has distinct roots, and does not handle the case for roots at the origin (s=0). Initial conditions must be zero. Differential equations may be input to CFORM in two forms - polynomial and product of factors. In some linear control analyses, it may be more appropriate to use a related program, Linear Control System Design and Analysis (KSC-11376), which uses root locus and frequency response methods. CFORM was written in VAX FORTRAN for a VAX 11/780 under VAX VMS 4.7. It has a central memory requirement of 30K. CFORM was developed in 1987.

  7. Reduction of observer order by differentiation, almost controllability subspace covers and minimal order PID-observers

    NARCIS (Netherlands)

    TRENTELMAN, HL

    1984-01-01

    This note generalizes the geometric theory around minimal and reduced order observers to the situation in which differentiation of certain components of the observed output is allowed. A geometric theory involving the notion of PID-observer is introduced, using the concept of almost complementary

  8. Differential Polarization Nonlinear Optical Microscopy with Adaptive Optics Controlled Multiplexed Beams

    Directory of Open Access Journals (Sweden)

    Virginijus Barzda

    2013-09-01

    Full Text Available Differential polarization nonlinear optical microscopy has the potential to become an indispensable tool for structural investigations of ordered biological assemblies and microcrystalline aggregates. Their microscopic organization can be probed through fast and sensitive measurements of nonlinear optical signal anisotropy, which can be achieved with microscopic spatial resolution by using time-multiplexed pulsed laser beams with perpendicular polarization orientations and photon-counting detection electronics for signal demultiplexing. In addition, deformable membrane mirrors can be used to correct for optical aberrations in the microscope and simultaneously optimize beam overlap using a genetic algorithm. The beam overlap can be achieved with better accuracy than diffraction limited point-spread function, which allows to perform polarization-resolved measurements on the pixel-by-pixel basis. We describe a newly developed differential polarization microscope and present applications of the differential microscopy technique for structural studies of collagen and cellulose. Both, second harmonic generation, and fluorescence-detected nonlinear absorption anisotropy are used in these investigations. It is shown that the orientation and structural properties of the fibers in biological tissue can be deduced and that the orientation of fluorescent molecules (Congo Red, which label the fibers, can be determined. Differential polarization microscopy sidesteps common issues such as photobleaching and sample movement. Due to tens of megahertz alternating polarization of excitation pulses fast data acquisition can be conveniently applied to measure changes in the nonlinear signal anisotropy in dynamically changing in vivo structures.

  9. A 3D magnetic tissue stretcher for remote mechanical control of embryonic stem cell differentiation.

    Science.gov (United States)

    Du, Vicard; Luciani, Nathalie; Richard, Sophie; Mary, Gaëtan; Gay, Cyprien; Mazuel, François; Reffay, Myriam; Menasché, Philippe; Agbulut, Onnik; Wilhelm, Claire

    2017-09-12

    The ability to create a 3D tissue structure from individual cells and then to stimulate it at will is a major goal for both the biophysics and regenerative medicine communities. Here we show an integrated set of magnetic techniques that meet this challenge using embryonic stem cells (ESCs). We assessed the impact of magnetic nanoparticles internalization on ESCs viability, proliferation, pluripotency and differentiation profiles. We developed magnetic attractors capable of aggregating the cells remotely into a 3D embryoid body. This magnetic approach to embryoid body formation has no discernible impact on ESC differentiation pathways, as compared to the hanging drop method. It is also the base of the final magnetic device, composed of opposing magnetic attractors in order to form embryoid bodies in situ, then stretch them, and mechanically stimulate them at will. These stretched and cyclic purely mechanical stimulations were sufficient to drive ESCs differentiation towards the mesodermal cardiac pathway.The development of embryoid bodies that are responsive to external stimuli is of great interest in tissue engineering. Here, the authors culture embryonic stem cells with magnetic nanoparticles and show that the presence of magnetic fields could affect their aggregation and differentiation.

  10. A regulatory transcriptional loop controls proliferation and differentiation in Drosophila neural stem cells.

    Directory of Open Access Journals (Sweden)

    Tetsuo Yasugi

    Full Text Available Neurogenesis is initiated by a set of basic Helix-Loop-Helix (bHLH transcription factors that specify neural progenitors and allow them to generate neurons in multiple rounds of asymmetric cell division. The Drosophila Daughterless (Da protein and its mammalian counterparts (E12/E47 act as heterodimerization factors for proneural genes and are therefore critically required for neurogenesis. Here, we demonstrate that Da can also be an inhibitor of the neural progenitor fate whose absence leads to stem cell overproliferation and tumor formation. We explain this paradox by demonstrating that Da induces the differentiation factor Prospero (Pros whose asymmetric segregation is essential for differentiation in one of the two daughter cells. Da co-operates with the bHLH transcription factor Asense, whereas the other proneural genes are dispensible. After mitosis, Pros terminates Asense expression in one of the two daughter cells. In da mutants, pros is not expressed, leading to the formation of lethal transplantable brain tumors. Our results define a transcriptional feedback loop that regulates the balance between self-renewal and differentiation in Drosophila optic lobe neuroblasts. They indicate that initiation of a neural differentiation program in stem cells is essential to prevent tumorigenesis.

  11. G-protein signaling leverages subunit-dependent membrane affinity to differentially control βγ translocation to intracellular membranes.

    Science.gov (United States)

    O'Neill, Patrick R; Karunarathne, W K Ajith; Kalyanaraman, Vani; Silvius, John R; Gautam, N

    2012-12-18

    Activation of G-protein heterotrimers by receptors at the plasma membrane stimulates βγ-complex dissociation from the α-subunit and translocation to internal membranes. This intermembrane movement of lipid-modified proteins is a fundamental but poorly understood feature of cell signaling. The differential translocation of G-protein βγ-subunit types provides a valuable experimental model to examine the movement of signaling proteins between membranes in a living cell. We used live cell imaging, mathematical modeling, and in vitro measurements of lipidated fluorescent peptide dissociation from vesicles to determine the mechanistic basis of the intermembrane movement and identify the interactions responsible for differential translocation kinetics in this family of evolutionarily conserved proteins. We found that the reversible translocation is mediated by the limited affinity of the βγ-subunits for membranes. The differential kinetics of the βγ-subunit types are determined by variations among a set of basic and hydrophobic residues in the γ-subunit types. G-protein signaling thus leverages the wide variation in membrane dissociation rates among different γ-subunit types to differentially control βγ-translocation kinetics in response to receptor activation. The conservation of primary structures of γ-subunits across mammalian species suggests that there can be evolutionary selection for primary structures that confer specific membrane-binding affinities and consequent rates of intermembrane movement.

  12. Fringe Controls Naïve CD4+T Cells Differentiation through Modulating Notch Signaling in Asthmatic Rat Models

    Science.gov (United States)

    Gu, Wen; Xu, Weiguo; Ding, Tao; Guo, Xuejun

    2012-01-01

    The ability of Notch signaling to regulate T helper cell development and differentiation has been widely accepted. Fringe, O-fucose-β1,3-N-acetylglucosaminyltransferases modulate Notch receptor expression and promote the Notch signaling pathway through receptor-ligand binding. In this study, we assayed the expression levels of three Fringe homologs in naive CD4+T cells in asthmatic rats. We found that Radical Fringe (Rfng) was highly expressed, whereas both Lunatic Fringe (Lfng) and Manic Fringe (Mfng) were expressed at low levels. Down-regulation of Rfng using siRNA, and overexpression of Lfng or Mfng enhanced Th1 subset lineages and diminished Th2 subset lineages. Notch signaling was more activated in asthmatic naïve CD4+T cells than in control cells, and Lfng, but not Mfng or Rfng, partly inhibited Notch signaling in asthmatic naïve CD4+T lymphocytes. Lfng overexpression resulted in significantly decreased Th2 cytokine production in asthma, which was the same effect as the GSI (γ-secretase inhibitor) treatment alone, but had an increased effect on Th1 cytokines than GSI treatment. Collectively, these data identify the essential role of Fringe modulating naïve CD4+T cells differentiation through Notch signaling. Lfng regulated Th2 cells differentiation via a Notch-dependent manner and Th1 cells differentiation via a Notch-independent manner. Fringe could be a therapeutic strategy for the management and prevention of allergic asthma. PMID:23071776

  13. Fringe controls naïve CD4(+)T cells differentiation through modulating notch signaling in asthmatic rat models.

    Science.gov (United States)

    Gu, Wen; Xu, Weiguo; Ding, Tao; Guo, Xuejun

    2012-01-01

    The ability of Notch signaling to regulate T helper cell development and differentiation has been widely accepted. Fringe, O-fucose-β1,3-N-acetylglucosaminyltransferases modulate Notch receptor expression and promote the Notch signaling pathway through receptor-ligand binding. In this study, we assayed the expression levels of three Fringe homologs in naive CD4(+)T cells in asthmatic rats. We found that Radical Fringe (Rfng) was highly expressed, whereas both Lunatic Fringe (Lfng) and Manic Fringe (Mfng) were expressed at low levels. Down-regulation of Rfng using siRNA, and overexpression of Lfng or Mfng enhanced Th1 subset lineages and diminished Th2 subset lineages. Notch signaling was more activated in asthmatic naïve CD4(+)T cells than in control cells, and Lfng, but not Mfng or Rfng, partly inhibited Notch signaling in asthmatic naïve CD4(+)T lymphocytes. Lfng overexpression resulted in significantly decreased Th2 cytokine production in asthma, which was the same effect as the GSI (γ-secretase inhibitor) treatment alone, but had an increased effect on Th1 cytokines than GSI treatment. Collectively, these data identify the essential role of Fringe modulating naïve CD4(+)T cells differentiation through Notch signaling. Lfng regulated Th2 cells differentiation via a Notch-dependent manner and Th1 cells differentiation via a Notch-independent manner. Fringe could be a therapeutic strategy for the management and prevention of allergic asthma.

  14. Hierarchical Velocity Control Based on Differential Flatness for a DC/DC Buck Converter-DC Motor System

    Directory of Open Access Journals (Sweden)

    R. Silva-Ortigoza

    2014-01-01

    Full Text Available This paper presents a hierarchical controller that carries out the angular velocity trajectory tracking task for a DC motor driven by a DC/DC Buck converter. The high level control is related to the DC motor and the low level control is dedicated to the DC/DC Buck converter; both controls are designed via differential flatness. The high level control provides a desired voltage profile for the DC motor to achieve the tracking of a desired angular velocity trajectory. Then, a low level control is designed to ensure that the output voltage of the DC/DC Buck converter tracks the voltage profile imposed by the high level control. In order to experimentally verify the hierarchical controller performance, a DS1104 electronic board from dSPACE and Matlab-Simulink are used. The switched implementation of the hierarchical average controller is accomplished by means of pulse width modulation. Experimental results of the hierarchical controller for the velocity trajectory tracking task show good performance and robustness against the uncertainties associated with different system parameters.

  15. EgoFlecto: stimulating being calm and in control through self-reflection in the context of driving

    DEFF Research Database (Denmark)

    Mosleh, Sara Said; Schmidt, Nele; Teisanu, Tudor

    2015-01-01

    commuting and propose a concept for enhancing this notion. Based on an iterative design process, we have developed a platform to test different ways of enhancing self-reflection in the car. The concept EgoFlecto is based on a seductive design strategy that aims to alter people's behavior simply through self-reflection...

  16. Protecting and rescuing the effectors: roles of differentiation and survival in the control of memory T cell development

    Directory of Open Access Journals (Sweden)

    Sema eKurtulus

    2013-01-01

    Full Text Available Vaccines, arguably the single most important intervention in improving human health, have exploited the phenomenon of immunological memory. The elicitation of memory T cells is often an essential part of successful long-lived protective immunity. Our understanding of T cell memory has been greatly aided by the development of TCR Tg mice and MHC tetrameric staining reagents that have allowed the precise tracking of antigen-specific T cell responses. Indeed, following acute infection or immunization, naïve T cells undergo a massive expansion culminating in the generation of a robust effector T cell population. This peak effector response is relatively short-lived and, while most effector T cells die by apoptosis, some remain and develop into memory cells. Although the molecular mechanisms underlying this cell fate decision remain incompletely defined, substantial progress has been made, particularly with regards to CD8+ T cells. For example, the effector CD8+ T cells generated during a response are heterogeneous, consisting of cells with more or less potential to develop into full-fledged memory cells. Development of CD8+ T cell memory is regulated by the transcriptional programs that control the differentiation and survival of effector T cells. While the type of antigenic stimulation and level of inflammation control effector CD8+ T cell differentiation, availability of cytokines and their ability to control expression and function of Bcl-2 family members governs their survival. These distinct differentiation and survival programs may allow for finer therapeutic intervention to control both the quality and quantity of CD8+ T cell memory. Effector to memory transition of CD4+ T cells is less well characterized than CD8+ T cells, emerging details will be discussed. This review will focus on the recent progress made in our understanding of the mechanisms underlying the development of T cell memory with an emphasis on factors controlling survival of

  17. The control of human mesenchymal cell differentiation using nanoscale symmetry and disorder

    Science.gov (United States)

    Dalby, Matthew J.; Gadegaard, Nikolaj; Tare, Rahul; Andar, Abhay; Riehle, Mathis O.; Herzyk, Pawel; Wilkinson, Chris D. W.; Oreffo, Richard O. C.

    2007-12-01

    A key tenet of bone tissue engineering is the development of scaffold materials that can stimulate stem cell differentiation in the absence of chemical treatment to become osteoblasts without compromising material properties. At present, conventional implant materials fail owing to encapsulation by soft tissue, rather than direct bone bonding. Here, we demonstrate the use of nanoscale disorder to stimulate human mesenchymal stem cells (MSCs) to produce bone mineral in vitro, in the absence of osteogenic supplements. This approach has similar efficiency to that of cells cultured with osteogenic media. In addition, the current studies show that topographically treated MSCs have a distinct differentiation profile compared with those treated with osteogenic media, which has implications for cell therapies.

  18. The transcriptional network that controls growth arrest and differentiation in a human myeloid leukemia cell line

    DEFF Research Database (Denmark)

    Suzuki, Harukazu; Forrest, Alistair R R; van Nimwegen, Erik

    2009-01-01

    , we identified the key transcription regulators, their time-dependent activities and target genes. Systematic siRNA knockdown of 52 transcription factors confirmed the roles of individual factors in the regulatory network. Our results indicate that cellular states are constrained by complex networks......Using deep sequencing (deepCAGE), the FANTOM4 study measured the genome-wide dynamics of transcription-start-site usage in the human monocytic cell line THP-1 throughout a time course of growth arrest and differentiation. Modeling the expression dynamics in terms of predicted cis-regulatory sites...... involving both positive and negative regulatory interactions among substantial numbers of transcription factors and that no single transcription factor is both necessary and sufficient to drive the differentiation process....

  19. Brief psychosocial therapy for the treatment of agitation in Alzheimer disease (the CALM-AD trial).

    Science.gov (United States)

    Ballard, Clive; Brown, Richard; Fossey, Jane; Douglas, Simon; Bradley, Paul; Hancock, Judith; James, Ian A; Juszczak, Edmund; Bentham, Peter; Burns, Alistair; Lindesay, James; Jacoby, Robin; O'Brien, John; Bullock, Roger; Johnson, Tony; Holmes, Clive; Howard, Robert

    2009-09-01

    Good practice guidelines state that a psychological intervention should usually precede pharmacotherapy, but there are no data evaluating the feasibility of psychological interventions used in this way. At the first stage of a randomized blinded placebo-controlled trial, 318 patients with Alzheimer disease (AD) with clinically significant agitated behavior were treated in an open design with a psychological intervention (brief psychosocial therapy [BPST]) for 4 weeks, preceding randomization to pharmacotherapy. The therapy involved social interaction, personalized music, or removal of environmental triggers. Overall, 318 patients with AD completed BPST with an improvement of 5.6 points on the total Cohen-Mansfield Agitation Inventory (CMAI; mean [SD], 63.3 [16.0] to 57.7 [18.4], t = 4.8, df = 317, p 95% of patients. More detailed evaluation of outcome was completed for the 198 patients with AD from these centers, who experienced a mean improvement of 6.6 points on the total CMAI (mean [SD], 62.2 [14.3] to 55.6 [15.8], t = 6.5, df = 197, p < 0.0001). Overall, 43% of participants achieved a 30% improvement in their level of agitation. The specific attributable benefits of BPST cannot be determined from an open trial. However, the BPST therapy was feasible and was successfully delivered according to an operationalized manual. The encouraging outcome indicates the need for a randomized controlled trial of BPST.

  20. Calm and Smart? A Selective Review on Effects of Meditation on Decision Making

    Directory of Open Access Journals (Sweden)

    Sai eSun

    2015-07-01

    Full Text Available Over the past two decades, there has been a growing interest in the use of meditation to improve cognitive performance, emotional balance, and well-being. As a consequence, research into the psychological effects and neural mechanisms of meditation has been accumulating. Whether and how meditation affects decision making is not yet clear. Here, we review evidence from behavioral and neuroimaging studies and summarize the effects of meditation on social and nonsocial economic decision making. Research suggests that meditation modulates brain activities associated with cognitive control, emotion regulation and empathy, and leads to improved nonsocial and social decision making. Accordingly, we propose an integrative model in which cognitive control, emotional regulation, and empathic concern mediate the effects of meditation on decision making. This model provides insights into the mechanisms by which meditation affects the decision making process. More evidence is needed to test our explanatory model and to explore the function of specific brain areas and their interactive effects on decision making during meditation training.

  1. Calm and smart? A selective review of meditation effects on decision making.

    Science.gov (United States)

    Sun, Sai; Yao, Ziqing; Wei, Jaixin; Yu, Rongjun

    2015-01-01

    Over the past two decades, there has been a growing interest in the use of meditation to improve cognitive performance, emotional balance, and well-being. As a consequence, research into the psychological effects and neural mechanisms of meditation has been accumulating. Whether and how meditation affects decision making is not yet clear. Here, we review evidence from behavioral and neuroimaging studies and summarize the effects of meditation on social and non-social economic decision making. Research suggests that meditation modulates brain activities associated with cognitive control, emotion regulation and empathy, and leads to improved non-social and social decision making. Accordingly, we propose an integrative model in which cognitive control, emotional regulation, and empathic concern mediate the effects of meditation on decision making. This model provides insights into the mechanisms by which meditation affects the decision making process. More evidence is needed to test our explanatory model and to explore the function of specific brain areas and their interactive effects on decision making during meditation training.

  2. Differential effects of a visuospatial attention task on measures of postural control in young and older adults.

    Science.gov (United States)

    Peterson, Jeffrey J; Keenan, Kevin G

    2018-02-01

    The purpose of this study was to examine the influence of a visuospatial attention task on three measures of postural control in young and older adults. 20 young (19-36  years) and 20 older (67-91 years) adults performed a choice stepping response time (CSRT) task, a submaximal dorsiflexion force steadiness task, and quiet standing in 3 bilateral stances. All tasks were performed with and without a visuospatial (VS) attention task that involved visualizing a star moving within a 2 × 2 grid. CSRT increased with the addition of the VS task in both groups (p   .084). The findings suggest that visuospatial attention differentially affects postural control in young and older adults and the effect is task-specific. These findings suggest the need to include stepping and force control tasks to further determine what role visuospatial attention plays in postural control. Copyright © 2017. Published by Elsevier Ltd.

  3. SREBP-1c/MicroRNA 33b Genomic Loci Control Adipocyte Differentiation

    Science.gov (United States)

    Price, Nathan L.; Holtrup, Brandon; Kwei, Stephanie L.; Wabitsch, Martin; Rodeheffer, Matthew; Bianchini, Laurence; Suárez, Yajaira

    2016-01-01

    White adipose tissue (WAT) is essential for maintaining metabolic function, especially during obesity. The intronic microRNAs miR-33a and miR-33b, located within the genes encoding sterol regulatory element-binding protein 2 (SREBP-2) and SREBP-1, respectively, are transcribed in concert with their host genes and function alongside them to regulate cholesterol, fatty acid, and glucose metabolism. SREBP-1 is highly expressed in mature WAT and plays a critical role in promoting in vitro adipocyte differentiation. It is unknown whether miR-33b is induced during or involved in adipogenesis. This is in part due to loss of miR-33b in rodents, precluding in vivo assessment of the impact of miR-33b using standard mouse models. This work demonstrates that miR-33b is highly induced upon differentiation of human preadipocytes, along with SREBP-1. We further report that miR-33b is an important regulator of adipogenesis, as inhibition of miR-33b enhanced lipid droplet accumulation. Conversely, overexpression of miR-33b impaired preadipocyte proliferation and reduced lipid droplet formation and the induction of peroxisome proliferator-activated receptor γ (PPARγ) target genes during differentiation. These effects may be mediated by targeting of HMGA2, cyclin-dependent kinase 6 (CDK6), and other predicted miR-33b targets. Together, these findings demonstrate a novel role of miR-33b in the regulation of adipocyte differentiation, with important implications for the development of obesity and metabolic disease. PMID:26830228

  4. Scoparone attenuates RANKL-induced osteoclastic differentiation through controlling reactive oxygen species production and scavenging

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Sang-Hyun; Jang, Hae-Dong, E-mail: haedong@hnu.kr

    2015-02-15

    Scoparone, one of the bioactive components of Artemisia capillaris Thunb, has various biological properties including immunosuppressive, hepatoprotective, anti-allergic, anti-inflammatory, and antioxidant effects. This study aims at evaluating the anti-osteoporotic effect of scoparone and its underlying mechanism in vitro. Scoparone demonstrated potent cellular antioxidant capacity. It was also found that scoparone inhibited the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and suppressed cathepsin K and tartrate-resistant acid phosphatase (TRAP) expression via c-jun N-terminal kinase (JNK)/extracellular signal-regulated kinase (ERK)/p38-mediated c-Fos–nuclear factor of activated T cells, cytoplasmic 1 (NFATc1) signaling pathway. During osteoclast differentiation, the production of general reactive oxygen species (ROS) and superoxide anions was dose-dependently attenuated by scoparone. In addition, scoparone diminished NADPH (nicotinamide adenine dinucleotide phosphate) oxidase 1 (Nox1) expression and activation via the tumor necrosis factor receptor-associated factor 6 (TRAF6)–cSrc–phosphatidylinositol 3-kinase (PI3k) signaling pathway and prevented the disruption of mitochondrial electron transport chain system. Furthermore, scoparone augmented the expression of superoxide dismutase 1 (SOD1) and catalase (CAT). The overall results indicate that the inhibitory effect of scoparone on RANKL-induced osteoclast differentiation is attributed to the suppressive effect on ROS and superoxide anion production by inhibiting Nox1 expression and activation and protecting the mitochondrial electron transport chain system and the scavenging effect of ROS resulting from elevated SOD1 and CAT expression. - Highlights: • Scoparone dose-dependently inhibited RANKL-induced osteoclast differentiation. • Scoparone diminished general ROS and superoxide anions in a dose-dependent manner. • Scoparone inhibited Nox1 expression and

  5. Quality Control in Survey Design: Evaluating a Survey of Educators’ Attitudes Concerning Differentiated Compensation

    OpenAIRE

    Kelly D. Bradley; Michael Peabody; Shannon O. Sampson

    2015-01-01

    This study utilized the Rasch model to assess the quality of a survey instrument designed to measure attitudes of administrators and teachers concerning a differentiated teacher compensation program piloted in Kentucky.  Researchers addressing potentially contentious issues should ensure their methods stand up to rigorous criticism.  The results indicate that the rating scale does not function as expected, with items being too easy to endorse.  Future iterations of this survey should be revis...

  6. LIX1 regulates YAP1 activity and controls the proliferation and differentiation of stomach mesenchymal progenitors.

    Science.gov (United States)

    McKey, Jennifer; Martire, Delphine; de Santa Barbara, Pascal; Faure, Sandrine

    2016-04-28

    Smooth muscle cell (SMC) plasticity maintains the balance between differentiated SMCs and proliferative mesenchymal progenitors, crucial for muscular tissue homeostasis. Studies on the development of mesenchymal progenitors into SMCs have proven useful in identifying molecular mechanisms involved in digestive musculature plasticity in physiological and pathological conditions. Here, we show that Limb Expression 1 (LIX1) molecularly defines the population of mesenchymal progenitors in the developing stomach. Using in vivo functional approaches in the chick embryo, we demonstrate that LIX1 is a key regulator of stomach SMC development. We show that LIX1 is required for stomach SMC determination to regulate the expression of the pro-proliferative gene YAP1 and mesenchymal cell proliferation. However, as stomach development proceeds, sustained LIX1 expression has a negative impact on further SMC differentiation and this is associated with a decrease in YAP1 activity. We demonstrate that expression of LIX1 must be tightly regulated to allow fine-tuning of the transcript levels and state of activation of the pro-proliferative transcriptional coactivator YAP1 to regulate proliferation rates of stomach mesenchymal progenitors and their differentiation. Our data highlight dual roles for LIX1 and YAP1 and provide new insights into the regulation of cell density-dependent proliferation, which is essential for the development and homeostasis of organs.

  7. Do Children with Better Inhibitory Control Donate More? Differentiating between Early and Middle Childhood and Cool and Hot Inhibitory Control

    Directory of Open Access Journals (Sweden)

    Jian Hao

    2017-12-01

    Full Text Available Inhibitory control may play an important part in prosocial behavior, such as donating behavior. However, it is not clear at what developmental stage inhibitory control becomes associated with donating behavior and which aspects of inhibitory control are related to donating behavior during development in early to middle childhood. The present study aimed to clarify these issues with two experiments. In Experiment 1, 103 3- to 5-year-old preschoolers completed cool (Stroop-like and hot (delay of gratification inhibitory control tasks and a donating task. The results indicated that there were no relationships between cool or hot inhibitory control and donating behavior in the whole group and each age group of the preschoolers. In Experiment 2, 140 elementary school children in Grades 2, 4, and 6 completed cool (Stroop-like and hot (delay of gratification inhibitory control tasks and a donating task. The results showed that inhibitory control was positively associated with donating behavior in the whole group. Cool and hot inhibitory control respectively predicted donating behavior in the second and sixth graders. Therefore, the present study reveals that donating behavior increasingly relies on specific inhibitory control, i.e., hot inhibitory control as children grow in middle childhood.

  8. Differential Evolution Based IDWNN Controller for Fault Ride-Through of Grid-Connected Doubly Fed Induction Wind Generators.

    Science.gov (United States)

    Manonmani, N; Subbiah, V; Sivakumar, L

    2015-01-01

    The key objective of wind turbine development is to ensure that output power is continuously increased. It is authenticated that wind turbines (WTs) supply the necessary reactive power to the grid at the time of fault and after fault to aid the flowing grid voltage. At this juncture, this paper introduces a novel heuristic based controller module employing differential evolution and neural network architecture to improve the low-voltage ride-through rate of grid-connected wind turbines, which are connected along with doubly fed induction generators (DFIGs). The traditional crowbar-based systems were basically applied to secure the rotor-side converter during the occurrence of grid faults. This traditional controller is found not to satisfy the desired requirement, since DFIG during the connection of crowbar acts like a squirrel cage module and absorbs the reactive power from the grid. This limitation is taken care of in this paper by introducing heuristic controllers that remove the usage of crowbar and ensure that wind turbines supply necessary reactive power to the grid during faults. The controller is designed in this paper to enhance the DFIG converter during the grid fault and this controller takes care of the ride-through fault without employing any other hardware modules. The paper introduces a double wavelet neural network controller which is appropriately tuned employing differential evolution. To validate the proposed controller module, a case study of wind farm with 1.5 MW wind turbines connected to a 25 kV distribution system exporting power to a 120 kV grid through a 30 km 25 kV feeder is carried out by simulation.

  9. Differential Evolution Based IDWNN Controller for Fault Ride-Through of Grid-Connected Doubly Fed Induction Wind Generators

    Directory of Open Access Journals (Sweden)

    N. Manonmani

    2015-01-01

    Full Text Available The key objective of wind turbine development is to ensure that output power is continuously increased. It is authenticated that wind turbines (WTs supply the necessary reactive power to the grid at the time of fault and after fault to aid the flowing grid voltage. At this juncture, this paper introduces a novel heuristic based controller module employing differential evolution and neural network architecture to improve the low-voltage ride-through rate of grid-connected wind turbines, which are connected along with doubly fed induction generators (DFIGs. The traditional crowbar-based systems were basically applied to secure the rotor-side converter during the occurrence of grid faults. This traditional controller is found not to satisfy the desired requirement, since DFIG during the connection of crowbar acts like a squirrel cage module and absorbs the reactive power from the grid. This limitation is taken care of in this paper by introducing heuristic controllers that remove the usage of crowbar and ensure that wind turbines supply necessary reactive power to the grid during faults. The controller is designed in this paper to enhance the DFIG converter during the grid fault and this controller takes care of the ride-through fault without employing any other hardware modules. The paper introduces a double wavelet neural network controller which is appropriately tuned employing differential evolution. To validate the proposed controller module, a case study of wind farm with 1.5 MW wind turbines connected to a 25 kV distribution system exporting power to a 120 kV grid through a 30 km 25 kV feeder is carried out by simulation.

  10. Predictive Control of the Blood Glucose Level in Type I Diabetic Patient Using Delay Differential Equation Wang Model.

    Science.gov (United States)

    Esna-Ashari, Mojgan; Zekri, Maryam; Askari, Masood; Khalili, Noushin

    2017-01-01

    Because of increasing risk of diabetes, the measurement along with control of blood sugar has been of great importance in recent decades. In type I diabetes, because of the lack of insulin secretion, the cells cannot absorb glucose leading to low level of glucose. To control blood glucose (BG), the insulin must be injected to the body. This paper proposes a method for BG level regulation in type I diabetes. The control strategy is based on nonlinear model predictive control. The aim of the proposed controller optimized with genetics algorithms is to measure BG level each time and predict it for the next time interval. This merit causes a less amount of control effort, which is the rate of insulin delivered to the patient body. Consequently, this method can decrease the risk of hypoglycemia, a lethal phenomenon in regulating BG level in diabetes caused by a low BG level. Two delay differential equation models, namely Wang model and Enhanced Wang model, are applied as controller model and plant, respectively. The simulation results exhibit an acceptable performance of the proposed controller in meal disturbance rejection and robustness against parameter changes. As a result, if the nutrition of the person decreases instantly, the hypoglycemia will not happen. Furthermore, comparing this method with other works, it was shown that the new method outperforms previous studies.

  11. Keep calm and carry on: A crisis communication study of Cadbury and McDonalds

    Directory of Open Access Journals (Sweden)

    Telang Achyut

    2016-04-01

    Full Text Available Many organizations, at some point or another, have to face a crisis situation. In that scenario, the way in which the organization communicates makes or breaks the organization’s success in dealing with the crisis. Especially after the emergence of the social media, the impact of crisis communication on the process of successful crisis management has become even greater than before. Organizations have to take the initiative, to be proactive and create a plan for crisis communication. This paper is focused on the comparative study of the communication approaches followed by Cadbury and McDonalds during a period when the companies were dealing with a crisis. The findings of the content analysis show that a company should respond to the crisis as quickly as possible to avoid loss in terms of sales. The initial statement of the companies during a crisis should be clear, positive and through the right channel to help the company regain its reputation on the market. Advertising is the best way to convey the message across the world because the crisis situation that has come up in one market can soon catch-up in the other markets where the company operates. The company has to connect with the consumers on emotional grounds because the crisis breaks down the faith of the consumers in the company. The recovery actions that support the statements also play an important role during the crisis situation. By following the above-mentioned communication strategies, organizations can achieve damage control as well as turn the crisis into an opportunity to grow.

  12. Meal Replacement: Calming the Hot-State Brain Network of Appetite

    Directory of Open Access Journals (Sweden)

    Brielle ePaolini

    2014-03-01

    Full Text Available There is a growing awareness in the field of neuroscience that the self-regulation of eating behavior is driven by complex networks within the brain. These networks may be vulnerable to hot states which people can move into and out of dynamically throughout the course of a day as a function of changes in affect or visceral cues. The goal of the current study was to identify and determine differences in the Hot-state Brain Network of Appetite (HBN-A that exists after a brief period of food restraint followed either by the consumption of a meal replacement (MR or water. Fourteen overweight/obese adults came to our laboratory on two different occasions. Both times they consumed a controlled breakfast meal and then were restricted from eating for 2.5 hours prior to an MRI scan. On one visit, they consumed a meal replacement (MR liquid meal after this period of food restriction; on the other visit they consumed an equal amount of water. After these manipulations, the participants underwent a resting fMRI scan. Our first study aim employed an exploratory, data-driven approach to identify hubs relevant to the HBN-A. Using data from the water condition, five regions were found to be the hubs or nodes of the HBN-A: insula, anterior cingulated cortex, the superior temporal pole, the amygdala, and the hippocampus. We then demonstrated that the consumption of a liquid MR dampened interconnectivity between the nodes of the HBN-A as compared to water. Importantly and consistent with these network data, the consumption of a MR beverage also lowered state cravings and hunger.

  13. Meal replacement: calming the hot-state brain network of appetite.

    Science.gov (United States)

    Paolini, Brielle M; Laurienti, Paul J; Norris, James; Rejeski, W Jack

    2014-01-01

    There is a growing awareness in the field of neuroscience that the self-regulation of eating behavior is driven by complex networks within the brain. These networks may be vulnerable to "hot states" which people can move into and out of dynamically throughout the course of a day as a function of changes in affect or visceral cues. The goal of the current study was to identify and determine differences in the Hot-state Brain Network of Appetite (HBN-A) that exists after a brief period of food restraint followed either by the consumption of a meal replacement (MR) or water. Fourteen overweight/obese adults came to our laboratory on two different occasions. Both times they consumed a controlled breakfast meal and then were restricted from eating for 2.5 h prior to an MRI scan. On one visit, they consumed a meal replacement (MR) liquid meal after this period of food restriction; on the other visit they consumed an equal amount of water. After these manipulations, the participants underwent a resting fMRI scan. Our first study aim employed an exploratory, data-driven approach to identify hubs relevant to the HBN-A. Using data from the water condition, five regions were found to be the hubs or nodes of the HBN-A: insula, anterior cingulated cortex, the superior temporal pole, the amygdala, and the hippocampus. We then demonstrated that the consumption of a liquid MR dampened interconnectivity between the nodes of the HBN-A as compared to water. Importantly and consistent with these network data, the consumption of a MR beverage also lowered state cravings and hunger.

  14. Does giving brief information keep patients calm during different oral surgical procedures?

    Science.gov (United States)

    Cabbar, Fatih; Burdurlu, Muammer Çağrı; Tomruk, Ceyda Özçakır

    2018-04-16

    Dental anxiety may play a central role in the oral health status and treatment outcomes of oral surgical procedures. The study aimed to investigate the effect that brief written information has over patients undergoing oral surgical procedures and to evaluate factors that may cause anxiety. A prospective study was performed on 38 mandibular third molar surgery patients (mean age 26.74 ± 6.44 years) and 56 implant surgery patients (mean age 49.13 ± 15.11 years). Each group was divided into two subgroups, and written information, explaining what they could expect and details about the procedure, was provided to study groups. The Spielberger State-Trait Anxiety Inventory was used to measure state (STAI-S) and trait anxiety (STAI-T). The visual analog scale (VAS) was used for pain scores preoperatively and on days 1, 3, 5, and 7. Demographic data and intraoperative behaviors of patients were recorded. All groups had similar anxiety scores at baseline. Preoperative STAI-S and VAS scores were similar between study and control groups (P > .05). Study groups showed significantly lower mean intraoperative anxiety levels (P < .05). The implant group had a significantly lower VAS score (P < .05). STAI-T and preoperative STAI-S were not related to VAS. Postoperative STAI-S and VAS and recuperation were correlated (P < .05). Women showed significantly higher anxiety and VAS scores. The patients who received written information did not report lower anxiety scores. However, improved patient cooperation could be achieved with this method. Different surgical procedures may cause anxiety for different reasons.

  15. Substrate Stiffness Controls Osteoblastic and Chondrocytic Differentiation of Mesenchymal Stem Cells without Exogenous Stimuli.

    Directory of Open Access Journals (Sweden)

    Rene Olivares-Navarrete

    Full Text Available Stem cell fate has been linked to the mechanical properties of their underlying substrate, affecting mechanoreceptors and ultimately leading to downstream biological response. Studies have used polymers to mimic the stiffness of extracellular matrix as well as of individual tissues and shown mesenchymal stem cells (MSCs could be directed along specific lineages. In this study, we examined the role of stiffness in MSC differentiation to two closely related cell phenotypes: osteoblast and chondrocyte. We prepared four methyl acrylate/methyl methacrylate (MA/MMA polymer surfaces with elastic moduli ranging from 0.1 MPa to 310 MPa by altering monomer concentration. MSCs were cultured in media without exogenous growth factors and their biological responses were compared to committed chondrocytes and osteoblasts. Both chondrogenic and osteogenic markers were elevated when MSCs were grown on substrates with stiffness <10 MPa. Like chondrocytes, MSCs on lower stiffness substrates showed elevated expression of ACAN, SOX9, and COL2 and proteoglycan content; COMP was elevated in MSCs but reduced in chondrocytes. Substrate stiffness altered levels of RUNX2 mRNA, alkaline phosphatase specific activity, osteocalcin, and osteoprotegerin in osteoblasts, decreasing levels on the least stiff substrate. Expression of integrin subunits α1, α2, α5, αv, β1, and β3 changed in a stiffness- and cell type-dependent manner. Silencing of integrin subunit beta 1 (ITGB1 in MSCs abolished both osteoblastic and chondrogenic differentiation in response to substrate stiffness. Our results suggest that substrate stiffness is an important mediator of osteoblastic and chondrogenic differentiation, and integrin β1 plays a pivotal role in this process.

  16. E-drive with electrically controlled differential; E-Antrieb mit elektrisch geregeltem Differenzial

    Energy Technology Data Exchange (ETDEWEB)

    Smetana, Tomas; Biermann, Thorsten [Schaeffler Technologies GmbH und Co. KG, Herzogenaurach (Germany); Rohe, Marco [AFT Atlas Fahrzeugtechnik GmbH, Werdohl (Germany); Heinrich, Wolfgang [IDAM, Suhl (Germany)

    2011-10-15

    Schaeffler is presenting an all-wheel drive electric vehicle named 'Active eDrive'. The name is intended principally to convey innovation and the USP of the drive system: an electric differential with a torque vectoring function. The system combines the final drive with intelligent transverse torque distribution which, when used on axles, enables the distribution of torque over the longitudinal axis of the vehicle. The final drive can be integrated in both electric and hybrid vehicles with or without a range extender capability. The authors first explain the mechanical requirements and then describe the electrical systems that are intended to fulfill these. (orig.)

  17. Global stability, periodic solutions, and optimal control in a nonlinear differential delay model

    Directory of Open Access Journals (Sweden)

    Anatoli F. Ivanov

    2010-09-01

    Full Text Available A nonlinear differential equation with delay serving as a mathematical model of several applied problems is considered. Sufficient conditions for the global asymptotic stability and for the existence of periodic solutions are given. Two particular applications are treated in detail. The first one is a blood cell production model by Mackey, for which new periodicity criteria are derived. The second application is a modified economic model with delay due to Ramsey. An optimization problem for a maximal consumption is stated and solved for the latter.

  18. AGAMOUS controls GIANT KILLER, a multifunctional chromatin modifier in reproductive organ patterning and differentiation.

    Directory of Open Access Journals (Sweden)

    Kian-Hong Ng

    2009-11-01

    Full Text Available The Arabidopsis homeotic protein AGAMOUS (AG, a MADS domain transcription factor, specifies reproductive organ identity during flower development. Using a binding assay and expression analysis, we identified a direct target of AG, GIANT KILLER (GIK, which fine-tunes the expression of multiple genes downstream of AG. The GIK protein contains an AT-hook DNA binding motif that is widely found in chromosomal proteins and that binds to nuclear matrix attachment regions of DNA elements. Overexpression and loss of function of GIK cause wide-ranging defects in patterning and differentiation of reproductive organs. GIK directly regulates the expression of several key transcriptional regulators, including ETTIN/AUXIN RESPONSE FACTOR 3 (ETT/ARF3 that patterns the gynoecium, by binding to the matrix attachment regions of target promoters. Overexpression of GIK causes a swift and dynamic change in repressive histone modification in the ETT promoter. We propose that GIK acts as a molecular node downstream of the homeotic protein AG, regulating patterning and differentiation of reproductive organs through chromatin organization.

  19. Altered differential control of sympathetic outflow following sedentary conditions: Role of subregional neuroplasticity in the RVLM

    Directory of Open Access Journals (Sweden)

    Madhan Subramanian

    2016-07-01

    Full Text Available Despite the classically held belief of an all-or-none activation of the sympathetic nervous system, differential responses in sympathetic nerve activity (SNA can occur acutely at varying magnitudes and in opposing directions. Sympathetic nerves also appear to contribute differentially to various disease states including hypertension and heart failure. Previously we have reported that sedentary conditions enhanced responses of splanchnic SNA (SSNA but not lumbar SNA (LSNA to activation of the rostral ventrolateral medulla (RVLM in rats. Bulbospinal RVLM neurons from sedentary rats also exhibit increased dendritic branching in rostral regions of the RVLM. We hypothesized that regionally specific structural neuroplasticity would manifest as enhanced SSNA but not LSNA following activation of the rostral RVLM. To test this hypothesis, groups of physically active (10-12 weeks on running wheels or sedentary, male Sprague-Dawley rats were instrumented to record mean arterial pressure, LSNA and SSNA under Inactin anesthesia and during microinjections of glutamate (30 nl, 10 mM into multiple sites within the RVLM. Sedentary conditions enhanced SSNA but not LSNA responses and SSNA responses were enhanced at more central and rostral sites. Results suggest that enhanced SSNA responses in rostral RVLM coincide with enhanced dendritic branching in rostral RVLM observed previously. Identifying structural and functional neuroplasticity in specific populations of RVLM neurons may help identify new treatments for cardiovascular diseases, known to be more prevalent in sedentary individuals.

  20. Analysis of Nonlinear Duopoly Games with Product Differentiation: Stability, Global Dynamics, and Control

    Directory of Open Access Journals (Sweden)

    S. S. Askar

    2017-01-01

    Full Text Available Many researchers have used quadratic utility function to study its influences on economic games with product differentiation. Such games include Cournot, Bertrand, and a mixed-type game called Cournot-Bertrand. Within this paper, a cubic utility function that is derived from a constant elasticity of substitution production function (CES is introduced. This cubic function is more desirable than the quadratic one besides its amenability to efficiency analysis. Based on that utility a two-dimensional Cournot duopoly game with horizontal product differentiation is modeled using a discrete time scale. Two different types of games are studied in this paper. In the first game, firms are updating their output production using the traditional bounded rationality approach. In the second game, firms adopt Puu’s mechanism to update their productions. Puu’s mechanism does not require any information about the profit function; instead it needs both firms to know their production and their profits in the past time periods. In both scenarios, an explicit form for the Nash equilibrium point is obtained under certain conditions. The stability analysis of Nash point is considered. Furthermore, some numerical simulations are carried out to confirm the chaotic behavior of Nash equilibrium point. This analysis includes bifurcation, attractor, maximum Lyapunov exponent, and sensitivity to initial conditions.

  1. Microprocessor Activity Controls Differential miRNA Biogenesis In Vivo

    Directory of Open Access Journals (Sweden)

    Thomas Conrad

    2014-10-01

    Full Text Available In miRNA biogenesis, pri-miRNA transcripts are converted into pre-miRNA hairpins. The in vivo properties of this process remain enigmatic. Here, we determine in vivo transcriptome-wide pri-miRNA processing using next-generation sequencing of chromatin-associated pri-miRNAs. We identify a distinctive Microprocessor signature in the transcriptome profile from which efficiency of the endogenous processing event can be accurately quantified. This analysis reveals differential susceptibility to Microprocessor cleavage as a key regulatory step in miRNA biogenesis. Processing is highly variable among pri-miRNAs and a better predictor of miRNA abundance than primary transcription itself. Processing is also largely stable across three cell lines, suggesting a major contribution of sequence determinants. On the basis of differential processing efficiencies, we define functionality for short sequence features adjacent to the pre-miRNA hairpin. In conclusion, we identify Microprocessor as the main hub for diversified miRNA output and suggest a role for uncoupling miRNA biogenesis from host gene expression.

  2. Proposed megakaryocytic regulon of p53: the genes engaged to control cell cycle and apoptosis during megakaryocytic differentiation

    Science.gov (United States)

    Apostolidis, Pani A.; Lindsey, Stephan; Miller, William M.

    2012-01-01

    During endomitosis, megakaryocytes undergo several rounds of DNA synthesis without division leading to polyploidization. In primary megakaryocytes and in the megakaryocytic cell line CHRF, loss or knock-down of p53 enhances cell cycling and inhibits apoptosis, leading to increased polyploidization. To support the hypothesis that p53 suppresses megakaryocytic polyploidization, we show that stable expression of wild-type p53 in K562 cells (a p53-null cell line) attenuates the cells' ability to undergo polyploidization during megakaryocytic differentiation due to diminished DNA synthesis and greater apoptosis. This suggested that p53's effects during megakaryopoiesis are mediated through cell cycle- and apoptosis-related target genes, possibly by arresting DNA synthesis and promoting apoptosis. To identify candidate genes through which p53 mediates these effects, gene expression was compared between p53 knock-down (p53-KD) and control CHRF cells induced to undergo terminal megakaryocytic differentiation using microarray analysis. Among substantially downregulated p53 targets in p53-KD megakaryocytes were cell cycle regulators CDKN1A (p21) and PLK2, proapoptotic FAS, TNFRSF10B, CASP8, NOTCH1, TP53INP1, TP53I3, DRAM1, ZMAT3 and PHLDA3, DNA-damage-related RRM2B and SESN1, and actin component ACTA2, while antiapoptotic CKS1B, BCL2, GTSE1, and p53 family member TP63 were upregulated in p53-KD cells. Additionally, a number of cell cycle-related, proapoptotic, and cytoskeleton-related genes with known functions in megakaryocytes but not known to carry p53-responsive elements were differentially expressed between p53-KD and control CHRF cells. Our data support a model whereby p53 expression during megakaryopoiesis serves to control polyploidization and the transition from endomitosis to apoptosis by impeding cell cycling and promoting apoptosis. Furthermore, we identify a putative p53 regulon that is proposed to orchestrate these effects. PMID:22548738

  3. The splicing regulator PTBP1 controls the activity of the transcription factor Pbx1 during neuronal differentiation.

    Science.gov (United States)

    Linares, Anthony J; Lin, Chia-Ho; Damianov, Andrey; Adams, Katrina L; Novitch, Bennett G; Black, Douglas L

    2015-12-24

    The RNA-binding proteins PTBP1 and PTBP2 control programs of alternative splicing during neuronal development. PTBP2 was found to maintain embryonic splicing patterns of many synaptic and cytoskeletal proteins during differentiation of neuronal progenitor cells (NPCs) into early neurons. However, the role of the earlier PTBP1 program in embryonic stem cells (ESCs) and NPCs was not clear. We show that PTBP1 controls a program of neuronal gene expression that includes the transcription factor Pbx1. We identify exons specifically regulated by PTBP1 and not PTBP2 as mouse ESCs differentiate into NPCs. We find that PTBP1 represses Pbx1 exon 7 and the expression of the neuronal Pbx1a isoform in ESCs. Using CRISPR-Cas9 to delete regulatory elements for exon 7, we induce Pbx1a expression in ESCs, finding that this activates transcription of neuronal genes. Thus, PTBP1 controls the activity of Pbx1 to suppress its neuronal transcriptional program prior to induction of NPC development.

  4. Wnt/beta-catenin signaling interacts differentially with Ihh signaling in controlling endochondral bone and synovial joint formation.

    Science.gov (United States)

    Mak, Kingston Kinglun; Chen, Miao-Hsueh; Day, Timothy F; Chuang, Pao-Tien; Yang, Yingzi

    2006-09-01

    Both the Wnt/beta-catenin and Ihh signaling pathways play essential roles in crucial aspects of endochondral ossification: osteoblast differentiation, chondrocyte proliferation and hypertrophy. To understand the genetic interaction between these two signaling pathways, we have inactivated the beta-catenin gene and upregulated Ihh signaling simultaneously in the same cells during endochondral skeletal development using beta-catenin and patched 1 floxed alleles. We uncovered previously unexpected roles of Ihh signaling in synovial joint formation and the essential function of Wnt/beta-catenin signaling in regulating chondrocyte survival. More importantly, we found that Wnt and Ihh signaling interact with each other in distinct ways to control osteoblast differentiation, chondrocyte proliferation, hypertrophy, survival and synovial joint formation in the developing endochondral bone. Beta-catenin is required downstream of Ihh signaling and osterix expression for osteoblast differentiation. But in chondrocyte survival, beta-catenin is required upstream of Ihh signaling to inhibit chondrocyte apoptosis. In addition, Ihh signaling can inhibit chondrocyte hypertrophy and synovial joint formation independently of beta-catenin. However, there is a strong synergistic interaction between Wnt/beta-catenin and Ihh signaling in regulating synovial joint formation.

  5. Nonlinear Differential Equations and Feedback Control Design for the Urban-Rural Resident Pension Insurance in China

    Science.gov (United States)

    Wang, Lijian

    2015-12-01

    Facing many problems of the urban-rural resident pension insurance system in China, one should firstly make sure that this system can be optimized. This paper, based on the modern control theory, sets up differential equations as models to describe the urban-rural resident pension insurance system, and discusses the globally asymptotic stability in the sense of Liapunov for the urban-rural resident pension insurance system in the new equilibrium point. This research sets the stage for our further discussion, and it is theoretically important and convenient for optimizing the urban-rural resident pension insurance system.

  6. Differentiation of Serratia liquefaciens into swarm cells is controlled by the expression of the flhD master operon

    DEFF Research Database (Denmark)

    Eberl, L; Winson, MK; Sternberg, C

    1996-01-01

    The velocity with which a swarming colony of Serratia liquefaciens colonizes the surface of a suitable solid substratum was controlled by modulating the expression of the flhD master operon. In liquid medium, the stimulation of flhD expression resulted in filamentous, multinucleate......, and hyperflagellated cells that were indistinguishable from swarm cells isolated from the edge of a swarm colony. Thus, expression of the flhD master operon appears to play a central role in the process of swarm cell differentiation....

  7. Terminal Differentiation of Adult Hippocampal Progenitor Cells Is a Step Functionally Dissociable from Proliferation and Is Controlled by Tis21, Id3 and NeuroD2

    Directory of Open Access Journals (Sweden)

    Laura Micheli

    2017-07-01

    Full Text Available Cell proliferation and differentiation are interdependent processes. Here, we have asked to what extent the two processes of neural progenitor cell amplification and differentiation are functionally separated. Thus, we analyzed whether it is possible to rescue a defect of terminal differentiation in progenitor cells of the dentate gyrus, where new neurons are generated throughout life, by inducing their proliferation and/or their differentiation with different stimuli appropriately timed. As a model we used the Tis21 knockout mouse, whose dentate gyrus neurons, as demonstrated by us and others, have an intrinsic defect of terminal differentiation. We first tested the effect of two proliferative as well as differentiative neurogenic stimuli, one pharmacological (fluoxetine, the other cognitive (the Morris water maze (MWM training. Both effectively enhanced the number of new dentate gyrus neurons produced, and fluoxetine also reduced the S-phase length of Tis21 knockout dentate gyrus progenitor cells and increased the rate of differentiation of control cells, but neither factor enhanced the defective rate of differentiation. In contrast, the defect of terminal differentiation was fully rescued by in vivo infection of proliferating dentate gyrus progenitor cells with retroviruses either silencing Id3, an inhibitor of neural differentiation, or expressing NeuroD2, a proneural gene expressed in terminally differentiated dentate gyrus neurons. This is the first demonstration that NeuroD2 or the silencing of Id3 can activate the differentiation of dentate gyrus neurons, complementing a defect of differentiation. It also highlights how the rate of differentiation of dentate gyrus neurons is regulated genetically at several levels and that a neurogenic stimulus for amplification of neural stem/progenitor cells may not be sufficient in itself to modify this rate.

  8. Control of proliferation and osteogenic differentiation of human dental-pulp-derived stem cells by distinct surface structures.

    Science.gov (United States)

    Kolind, K; Kraft, D; Bøggild, T; Duch, M; Lovmand, J; Pedersen, F S; Bindslev, D A; Bünger, C E; Foss, M; Besenbacher, F

    2014-02-01

    The ability to control the behavior of stem cells provides crucial benefits, for example, in tissue engineering and toxicity/drug screening, which utilize the stem cell's capacity to engineer new tissues for regenerative purposes and the testing of new drugs in vitro. Recently, surface topography has been shown to influence stem cell differentiation; however, general trends are often difficult to establish due to differences in length scales, surface chemistries and detailed surface topographies. Here we apply a highly versatile screening approach to analyze the interplay of surface topographical parameters on cell attachment, morphology, proliferation and osteogenic differentiation of human mesenchymal dental-pulp-derived stem cells (DPSCs) cultured with and without osteogenic differentiation factors in the medium (ODM). Increasing the inter-pillar gap size from 1 to 6 μm for surfaces with small pillar sizes of 1 and 2 μm resulted in decreased proliferation and in more elongated cells with long pseudopodial protrusions. The same alterations of pillar topography, up to an inter-pillar gap size of 4 μm, also resulted in enhanced mineralization of DPSCs cultured without ODM, while no significant trend was observed for DPSCs cultured with ODM. Generally, cells cultured without ODM had a larger deposition of osteogenic markers on structured surfaces relative to the unstructured surfaces than what was found when culturing with ODM. We conclude that the topographical design of biomaterials can be optimized for the regulation of DPSC differentiation and speculate that the inclusion of ODM alters the ability of the cells to sense surface topographical cues. These results are essential in order to transfer the use of this highly proliferative, easily accessible stem cell into the clinic for use in cell therapy and regenerative medicine. Copyright © 2013 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  9. Imagined Positive Emotions and Inhibitory Control: The Differentiated Effect of Pride versus Happiness

    Science.gov (United States)

    Katzir, Maayan; Eyal, Tal; Meiran, Nachshon; Kessler, Yoav

    2010-01-01

    "Inhibitory control" is a cognitive mechanism that contributes to successful self-control (i.e., adherence to a long-term goal in the face of an interfering short-term goal). This research explored the effect of imagined positive emotional events on inhibition. The authors proposed that the influence of imagined emotions on inhibition…

  10. Why No Difference? A Controlled Flipped Classroom Study for an Introductory Differential Equations Course

    Science.gov (United States)

    Yong, Darryl; Levy, Rachel; Lape, Nancy

    2015-01-01

    Flipped classrooms have the potential to improve student learning and metacognitive skills as a result of increased time for active learning and group work and student control over pacing, when compared with traditional lecture-based courses. We are currently running a 4-year controlled study to examine the impact of flipping an Introductory…

  11. Control of germline stem cell self-renewal and differentiation in the Drosophila ovary: concerted actions of niche signals and intrinsic factors.

    Science.gov (United States)

    Xie, Ting

    2013-01-01

    In the Drosophila ovary, germline stem cells (GSCs) physically interact with their niche composed of terminal filament cells, cap cells, and possibly GSC-contacting escort cells (ECs). A GSC divides to generate a self-renewing stem cell that remains in the niche and a differentiating daughter that moves away from the niche. The GSC niche provides a bone morphogenetic protein (BMP) signal that maintains GSC self-renewal by preventing stem cell differentiation via repression of the differentiation-promoting gene bag of marbles (bam). In addition, it expresses E-cadherin, which mediates cell adhesion for anchoring GSCs in the niche, enabling continuous self-renewal. GSCs themselves also express different classes of intrinsic factors, including signal transducers, transcription factors, chromatin remodeling factors, translation regulators, and miRNAs, which control self-renewal by strengthening interactions with the niche and repressing various differentiation pathways. Differentiated GSC daughters, known as cystoblasts (CBs), also express distinct classes of intrinsic factors to inhibit self-renewal and promote germ cell differentiation. Surprisingly, GSC progeny are also dependent on their surrounding ECs for proper differentiation at least partly by preventing BMP from diffusing to the differentiated germ cell zone and by repressing ectopic BMP expression. Therefore, both GSC self-renewal and CB differentiation are controlled by collaborative actions of extrinsic signals and intrinsic factors. Copyright © 2012 Wiley Periodicals, Inc.

  12. Septin-Containing Barriers Control the Differential Inheritance of Cytoplasmic Elements

    Directory of Open Access Journals (Sweden)

    Alan Michael Tartakoff

    2013-01-01

    Full Text Available Fusion of haploid cells of Saccharomyces cerevisiae generates zygotes. We observe that the zygote midzone includes a septin annulus and differentially affects redistribution of supramolecular complexes and organelles. Redistribution across the midzone of supramolecular complexes (polysomes and Sup35p-GFP [PSI+] is unexpectedly delayed relative to soluble proteins; however, in [psi-] × [PSI+] crosses, all buds eventually receive Sup35p-GFP [PSI+]. Encounter between parental mitochondria is further delayed until septins relocate to the bud site, where they are required for repolarization of the actin cytoskeleton. This delay allows rationalization of the longstanding observation that terminal zygotic buds preferentially inherit a single mitochondrial genotype. The rate of redistribution of complexes and organelles determines whether their inheritance will be uniform.

  13. A Singular Differential Equation Stemming from an Optimal Control Problem in Financial Economics

    International Nuclear Information System (INIS)

    Brunovský, Pavol; Černý, Aleš; Winkler, Michael

    2013-01-01

    We consider the ordinary differential equation x 2 u'' = axu'+bu-c(u'-1) 2 , x ∈ (0,x 0 ), with a∈R, b∈R , c>0 and the singular initial condition u(0)=0, which in financial economics describes optimal disposal of an asset in a market with liquidity effects. It is shown in the paper that if a+b 0 then there are infinitely many continuous solutions with indistinguishable asymptotics near 0. Moreover, it is proved that in the latter case there is precisely one solution u corresponding to the choice x 0 =∞ which is such that 0≤u(x)≤x for all x>0, and that this solution is strictly increasing and concave

  14. A Singular Differential Equation Stemming from an Optimal Control Problem in Financial Economics

    Energy Technology Data Exchange (ETDEWEB)

    Brunovsky, Pavol, E-mail: brunovsky@fmph.uniba.sk [Comenius University Bratislava, Department of Applied Mathematics and Statistics (Slovakia); Cerny, Ales, E-mail: ales.cerny.1@city.ac.uk [City University London, Cass Business School (United Kingdom); Winkler, Michael, E-mail: michael.winkler@uni-due.de [Universitaet Paderborn, Institut fuer Mathematik (Germany)

    2013-10-15

    We consider the ordinary differential equation x{sup 2} u'' = axu'+bu-c(u'-1){sup 2}, x Element-Of (0,x{sub 0}), with a Element-Of R, b Element-Of R , c>0 and the singular initial condition u(0)=0, which in financial economics describes optimal disposal of an asset in a market with liquidity effects. It is shown in the paper that if a+b<0 then no continuous solutions exist, whereas if a+b>0 then there are infinitely many continuous solutions with indistinguishable asymptotics near 0. Moreover, it is proved that in the latter case there is precisely one solution u corresponding to the choice x{sub 0}={infinity} which is such that 0{<=}u(x){<=}x for all x>0, and that this solution is strictly increasing and concave.

  15. The linear variable differential transformer (LVDT) position sensor for gravitational wave interferometer low-frequency controls

    Energy Technology Data Exchange (ETDEWEB)

    Tariq, Hareem E-mail: htariq@ligo.caltech.edu; Takamori, Akiteru; Vetrano, Flavio; Wang Chenyang; Bertolini, Alessandro; Calamai, Giovanni; DeSalvo, Riccardo; Gennai, Alberto; Holloway, Lee; Losurdo, Giovanni; Marka, Szabolcs; Mazzoni, Massimo; Paoletti, Federico; Passuello, Diego; Sannibale, Virginio; Stanga, Ruggero

    2002-08-21

    Low-power, ultra-high-vacuum compatible, non-contacting position sensors with nanometer resolution and centimeter dynamic range have been developed, built and tested. They have been designed at Virgo as the sensors for low-frequency modal damping of Seismic Attenuation System chains in Gravitational Wave interferometers and sub-micron absolute mirror positioning. One type of these linear variable differential transformers (LVDTs) has been designed to be also insensitive to transversal displacement thus allowing 3D movement of the sensor head while still precisely reading its position along the sensitivity axis. A second LVDT geometry has been designed to measure the displacement of the vertical seismic attenuation filters from their nominal position. Unlike the commercial LVDTs, mostly based on magnetic cores, the LVDTs described here exert no force on the measured structure.

  16. Differential effect of race, education, gender, and language discrimination on glycemic control in adults with type 2 diabetes.

    Science.gov (United States)

    Reynolds, D Brice; Walker, Rebekah J; Campbell, Jennifer A; Egede, Leonard E

    2015-04-01

    Discrimination has been linked to negative health outcomes, but little research has investigated different types of discrimination to determine if some have a greater impact on outcomes. We examined the differential effect of discrimination based on race, level of education, gender, and language on glycemic control in adults with type 2 diabetes. Six hundred two patients with type 2 diabetes from two adult primary care clinics in the southeastern United States completed validated questionnaires. Questions included perceived discrimination because of race/ethnicity, level of education, sex/gender, or language. A multiple linear regression model assessed the differential effect of each type of perceived discrimination on glycemic control while adjusting for relevant covariates, including race, site, gender, marital status, duration of diabetes, number of years in school, number of hours worked per week, income, and health status. The mean age was 61.5 years, and the mean duration of diabetes was 12.3 years. Of the sample, 61.6% were men, and 64.9% were non-Hispanic black. In adjusted models, education discrimination remained significantly associated with glycemic control (β=0.47; 95% confidence interval, 0.03, 0.92). Race, gender and language discrimination were not significantly associated with poor glycemic control in either unadjusted or adjusted analyses. Discrimination based on education was found to be significantly associated with poor glycemic control. The findings suggest that education discrimination may be an important social determinant to consider when providing care to patients with type 2 diabetes and should be assessed separate from other types of discrimination, such as that based on race.

  17. Differential-drive mobile robot control using a cloud of particles approach

    Directory of Open Access Journals (Sweden)

    Walter Fetter Lages

    2016-12-01

    Full Text Available Common control systems for mobile robots include the use of some deterministic control law coupled with some pose estimation method, such as the extended Kalman filter, by considering the certainty equivalence principle. Recent approaches consider the use of partially observable Markov decision process strategies together with Bayesian estimators. These methods are well suited to handle the uncertainty in pose estimation but demand significant processing power. In order to reduce the required processing power and still allow for multimodal or non-Gaussian uncertain distributions, we propose a scheme based on a particle filter and a corresponding cloud of control signals. The approach avoids the use of the certainty equivalence principle by postponing the decision on the optimal estimate to the control stage. As the mapping between the pose space and the control action space is nonlinear and the best estimation of robot pose is uncertain, postponing the decision to the control space makes it possible to select a better control action in the presence of multimodal and non-Gaussian uncertainty models. Simulation results are presented.

  18. Active vibration control of vehicle suspension systems using sliding modes, differential flatness and generalized proportional-integral control

    Directory of Open Access Journals (Sweden)

    Esteban Chávez Conde

    2011-01-01

    Full Text Available En este artículo se presenta un enfoque de diseño de esquemas de control activo robusto para sistemas de suspensión de vehículos, usando técnicas de control Proporcional-Integral Generalizado, modos deslizantes y planitud diferencial, para atenuar vibraciones indeseables inducidas por perturbaciones de terreno irregular. Se proponen dos esquemas de control: uno de ellos emplea mediciones de posición y de velocidad y el otro requiere únicamente mediciones de posición. Se propone la reconstrucción integral de las derivadas de la salida plana para evitar el uso de sensores de velocidad y de aceleración, así como la información de perturbaciones de terreno desconocidas.

  19. Differential Impact of In Vivo CD8+ T Lymphocyte Depletion in Controller versus Progressor Simian Immunodeficiency Virus-Infected Macaques.

    Science.gov (United States)

    Chowdhury, Ankita; Hayes, Timothy L; Bosinger, Steven E; Lawson, Benton O; Vanderford, Thomas; Schmitz, Joern E; Paiardini, Mirko; Betts, Michael; Chahroudi, Ann; Estes, Jacob D; Silvestri, Guido

    2015-09-01

    Numerous studies have demonstrated that CD8(+) T lymphocytes suppress virus replication during human immunodeficiency virus (HIV)/simian immunodeficiency virus (SIV) infection. However, the mechanisms underlying this activity of T cells remain incompletely understood. Here, we conducted CD8(+) T lymphocyte depletion in 15 rhesus macaques (RMs) infected intravenously (i.v.) with SIVmac239. At day 70 postinfection, the animals (10 progressors with high viremia and 5 controllers with low viremia) were CD8 depleted by i.v. administration of the antibody M-T807R1. As expected, CD8 depletion resulted in increased virus replication, more prominently in controllers than progressors, which correlated inversely with predepletion viremia. Of note, the feature of CD8(+) T lymphocyte predepletion that correlated best with the increase in viremia postdepletion was the level of CD8(+) T-bet(+) lymphocytes. We next found that CD8 depletion resulted in a homogenous increase of SIV RNA in superficial and mesenteric lymph nodes, spleen, and the gastrointestinal tract of both controllers and progressors. Interestingly, the level of SIV DNA increased postdepletion in both CD4(+) central memory T lymphocytes (TCM) and CD4(+) effector memory T lymphocytes (TEM) in progressor RMs but decreased in the CD4(+) TCM of 4 out of 5 controllers. Finally, we found that CD8 depletion is associated with a greater increase in CD4(+) T lymphocyte activation (measured by Ki-67 expression) in controllers than in progressors. Overall, these data reveal a differential impact of CD8(+) T lymphocyte depletion between controller and progressor SIV-infected RMs, emphasizing the complexity of the in vivo antiviral role of CD8(+) T lymphocytes. In this study, we further dissect the impact of CD8(+) T lymphocytes on HIV/SIV replication during SIV infection. CD8(+) T lymphocyte depletion leads to a relatively homogenous increase in viral replication in peripheral blood and tissues. CD8(+) T lymphocyte depletion

  20. Location-based admission control for differentiated services in 3G cellular networks

    NARCIS (Netherlands)

    Núñez-Queija, R.; Tan, H.-P.

    2006-01-01

    Third generation wireless systems can simultaneously accommodate flow transmissions of users with widely heterogeneous applications. As resources are limited (particularly in the air interface), admission control is necessary to ensure that all active users are accommodated with sufficient capacity

  1. Differential games a mathematical theory with applications to warfare and pursuit, control and optimization

    CERN Document Server

    Isaacs, Rufus

    1999-01-01

    Definitive work draws on game theory, calculus of variations, and control theory to solve an array of problems: military, pursuit and evasion, athletic contests, many more. Detailed examples, formal calculations. 1965 edition.

  2. HLA-C -35kb expression SNP is associated with differential control of β-HPV infection in squamous cell carcinoma cases and controls.

    Directory of Open Access Journals (Sweden)

    Karin A Vineretsky

    Full Text Available A single nucleotide polymorphism (SNP 35 kb upstream of the HLA-C gene is associated with HLA-C expression, and the high expressing genotype (CC has been associated with HIV-I control. HLA-C is unique among the classical MHC class I molecules for its role in the control of viral infections and recognition of abnormal or missing self. This immunosurveillance is central to the pathogenesis of non-melanoma skin cancer (NMSC, and of squamous cell carcinoma (SCC in particular. While sun exposure is a major risk factor for these cancers, cutaneous infections with genus β-HPV have been implicated in the development of SCC. We hypothesized that the high expression HLA-C genotype is associated with β-HPV infections. Therefore, we investigated the association between β-HPV serology and the -35 kb SNP (rs9264942 in a population-based case-control study of 510 SCC cases and 608 controls. Among controls, the high expression -35 kb SNP genotype (CC reduced the likelihood of positive serology for multiple (≥2 β-HPV infections (OR = 0.49, 95% CI: 0.25-0.97, and β-HPV species 2 infection (OR = 0.43, 95% CI: 0.23-0.79. However, no association with β-HPV status was observed among SCC cases. Our findings suggest that underlying immunogenotype plays an important role in differential control of β-HPV in SCC cases and controls.

  3. Differentiating Between Precursor and Control Variables When Analyzing Reasoned Action Theories

    OpenAIRE

    Hennessy, Michael; Bleakley, Amy; Fishbein, Martin; Brown, Larry; DiClemente, Ralph; Romer, Daniel; Valois, Robert; Vanable, Peter A.; Carey, Michael P.; Salazar, Laura

    2009-01-01

    This paper highlights the distinction between precursor and control variables in the context of reasoned action theory. Here the theory is combined with structural equation modeling to demonstrate how age and past sexual behavior should be situated in a reasoned action analysis. A two wave longitudinal survey sample of African-American adolescents is analyzed where the target behavior is having vaginal sex. Results differ when age and past behavior are used as control variables and when they ...

  4. Calming the Monkey Mind

    Science.gov (United States)

    Eliuk, Kendra; Chorney, David

    2017-01-01

    Many of today's students are experiencing higher levels of stress and anxiety in school. The need for competitive grades, the desire to be seen as perfect in a digital society, and parental pressures are only some of the reasons that students are experiencing more stress. This increased stress has lead to an overworked mind for many youth, dubbed…

  5. A rank-based algorithm of differential expression analysis for small cell line data with statistical control.

    Science.gov (United States)

    Li, Xiangyu; Cai, Hao; Wang, Xianlong; Ao, Lu; Guo, You; He, Jun; Gu, Yunyan; Qi, Lishuang; Guan, Qingzhou; Lin, Xu; Guo, Zheng

    2017-10-13

    To detect differentially expressed genes (DEGs) in small-scale cell line experiments, usually with only two or three technical replicates for each state, the commonly used statistical methods such as significance analysis of microarrays (SAM), limma and RankProd (RP) lack statistical power, while the fold change method lacks any statistical control. In this study, we demonstrated that the within-sample relative expression orderings (REOs) of gene pairs were highly stable among technical replicates of a cell line but often widely disrupted after certain treatments such like gene knockdown, gene transfection and drug treatment. Based on this finding, we customized the RankComp algorithm, previously designed for individualized differential expression analysis through REO comparison, to identify DEGs with certain statistical control for small-scale cell line data. In both simulated and real data, the new algorithm, named CellComp, exhibited high precision with much higher sensitivity than the original RankComp, SAM, limma and RP methods. Therefore, CellComp provides an efficient tool for analyzing small-scale cell line data. © The Author 2017. Published by Oxford University Press.

  6. GM-CSF Controls Nonlymphoid Tissue Dendritic Cell Homeostasis but Is Dispensable for the Differentiation of Inflammatory Dendritic Cells

    Science.gov (United States)

    Greter, Melanie; Helft, Julie; Chow, Andrew; Hashimoto, Daigo; Mortha, Arthur; Agudo-Cantero, Judith; Bogunovic, Milena; Gautier, Emmanuel L.; Miller, Jennifer; Leboeuf, Marylene; Lu, Geming; Aloman, Costica; Brown, Brian D.; Pollard, Jeffrey W.; Xiong, Huabao; Randolph, Gwendalyn J.; Chipuk, Jerry E.; Frenette, Paul S.; Merad, Miriam

    2012-01-01

    SUMMARY GM-CSF (Csf-2) is a critical cytokine for the in vitro generation of dendritic cells (DCs) and is thought to control the development of inflammatory DCs and resident CD103+ DCs in some tissues. Here we showed that in contrast to the current understanding, Csf-2 receptor acts in the steady state to promote the survival and homeostasis of nonlymphoid tissue-resident CD103+ and CD11b+ DCs. Absence of Csf-2 receptor on lung DCs abrogated the induction of CD8+ T cell immunity after immunization with particulate antigens. In contrast, Csf-2 receptor was dispensable for the differentiation and innate function of inflammatory DCs during acute injuries. Instead, inflammatory DCs required Csf-1 receptor for their development. Thus, Csf-2 is important in vaccine-induced CD8+ T cell immunity through the regulation of nonlymphoid tissue DC homeostasis rather than control of inflammatory DCs in vivo. PMID:22749353

  7. Numerical algebra, matrix theory, differential-algebraic equations and control theory festschrift in honor of Volker Mehrmann

    CERN Document Server

    Bollhöfer, Matthias; Kressner, Daniel; Mehl, Christian; Stykel, Tatjana

    2015-01-01

    This edited volume highlights the scientific contributions of Volker Mehrmann, a leading expert in the area of numerical (linear) algebra, matrix theory, differential-algebraic equations and control theory. These mathematical research areas are strongly related and often occur in the same real-world applications. The main areas where such applications emerge are computational engineering and sciences, but increasingly also social sciences and economics. This book also reflects some of Volker Mehrmann's major career stages. Starting out working in the areas of numerical linear algebra (his first full professorship at TU Chemnitz was in "Numerical Algebra," hence the title of the book) and matrix theory, Volker Mehrmann has made significant contributions to these areas ever since. The highlights of these are discussed in Parts I and II of the present book. Often the development of new algorithms in numerical linear algebra is motivated by problems in system and control theory. These and his later major work on ...

  8. Differentiation of Serratia liquefaciens into swarm cells is controlled by the expression of the flhD master operon

    DEFF Research Database (Denmark)

    Eberl, L; Winson, MK; Sternberg, C

    1996-01-01

    The velocity with which a swarming colony of Serratia liquefaciens colonizes the surface of a suitable solid substratum was controlled by modulating the expression of the flhD master operon. In liquid medium, the stimulation of flhD expression resulted in filamentous, multinucleate, and hyperflag......The velocity with which a swarming colony of Serratia liquefaciens colonizes the surface of a suitable solid substratum was controlled by modulating the expression of the flhD master operon. In liquid medium, the stimulation of flhD expression resulted in filamentous, multinucleate......, and hyperflagellated cells that were indistinguishable from swarm cells isolated from the edge of a swarm colony. Thus, expression of the flhD master operon appears to play a central role in the process of swarm cell differentiation....

  9. A Conserved MicroRNA Regulatory Circuit Is Differentially Controlled during Limb/Appendage Regeneration.

    Directory of Open Access Journals (Sweden)

    Benjamin L King

    Full Text Available Although regenerative capacity is evident throughout the animal kingdom, it is not equally distributed throughout evolution. For instance, complex limb/appendage regeneration is muted in mammals but enhanced in amphibians and teleosts. The defining characteristic of limb/appendage regenerative systems is the formation of a dedifferentiated tissue, termed blastema, which serves as the progenitor reservoir for regenerating tissues. In order to identify a genetic signature that accompanies blastema formation, we employ next-generation sequencing to identify shared, differentially regulated mRNAs and noncoding RNAs in three different, highly regenerative animal systems: zebrafish caudal fins, bichir pectoral fins and axolotl forelimbs.These studies identified a core group of 5 microRNAs (miRNAs that were commonly upregulated and 5 miRNAs that were commonly downregulated, as well as 4 novel tRNAs fragments with sequences conserved with humans. To understand the potential function of these miRNAs, we built a network of 1,550 commonly differentially expressed mRNAs that had functional relationships to 11 orthologous blastema-associated genes. As miR-21 was the most highly upregulated and most highly expressed miRNA in all three models, we validated the expression of known target genes, including the tumor suppressor, pdcd4, and TGFβ receptor subunit, tgfbr2 and novel putative target genes such as the anti-apoptotic factor, bcl2l13, Choline kinase alpha, chka and the regulator of G-protein signaling, rgs5.Our extensive analysis of RNA-seq transcriptome profiling studies in three regenerative animal models, that diverged in evolution ~420 million years ago, reveals a common miRNA-regulated genetic network of blastema genes. These comparative studies extend our current understanding of limb/appendage regeneration by identifying previously unassociated blastema genes and the extensive regulation by miRNAs, which could serve as a foundation for future

  10. Differential effects of controllable stress exposure on subsequent extinction learning in adult rats

    Directory of Open Access Journals (Sweden)

    Osnat eHadad-Ophir

    2016-01-01

    Full Text Available Deficits in fear extinction are thought to be related to various anxiety disorders. While failure to extinguish conditioned fear may result in pathological anxiety levels, the ability to quickly and efficiently attenuate learned fear through extinction processes can be extremely beneficial for the individual. One of the factors that may affect the efficiency of the extinction process is prior experience of stressful situations. In the current study, we examined whether exposure to controllable stress, which is suggested to induce stress resilience, can affect subsequent fear extinction. Here, following prolonged two-way shuttle (TWS avoidance training and a validation of acquired stress controllability, adult rats underwent either cued or contextual fear-conditioning (FC, followed by an extinction session. We further evaluated long lasting alterations of GABAergic targets in the medial pre-frontal cortex (mPFC, as these were implicated in FC and extinction and stress controllability. In cued, but not in contextual fear extinction, within-session extinction was enhanced following controllable stress compared to a control group. Interestingly, impaired extinction recall was detected in both extinction types following the stress procedure. Additionally, stress controllability-dependent alterations in GABAergic markers expression in infralimbic (IL, but not prelimbic (PL cortex, were detected. These alterations are proposed to be related to the within-session effect, but not the recall impairment. The results emphasize the contribution of prior experience on coping with subsequent stressful experiences. Moreover, the results emphasize that exposure to controllable stress does not generally facilitate future stress coping as previously claimed, but its effects are dependent on specific features of the events taking place.

  11. Differential accumulation and distribution of natural gas and its main controlling factors in the Sinian Dengying Fm, Sichuan Basin

    Directory of Open Access Journals (Sweden)

    Shugen Liu

    2015-01-01

    Full Text Available In order to disclose the genetic relationship between the hydrocarbon reservoirs and the transformation mechanism between ancient and modern gas reservoirs in the Sinian Dengying Fm in the Sichuan Basin, by using the drilling data, and geologic, geophysical and geochemical methods together, the differential accumulation and distribution of natural gas and its main controlling factors in this study area were identified following the idea of corroborating macroscopic, mesoscopic and microscopic results each other. The results demonstrate as follows. (1 The crude oil in the paleo-oil reservoirs of the Dengying Fm cracked into gas to form the early overpressure paleo-gas reservoirs 100 Ma. From 100 Ma to 20 Ma, the constant uplifting of the Sichuan Basin coupled with the shift of structural highs and the initial occurrence of Weiyuan anticline caused the adjustment of the early overpressure paleo-gas reservoirs into the late overpressure paleo-gas reservoirs. (2 With the increase of uplifting magnitude since 20 Ma, the formations overlying the Dengying Fm in Weiyuan structure experienced rapid erosion, resulting in decline of the caprock sealing ability and damage to the preservation conditions. Therefore, the natural gas in the Dengying Fm started to leak and dissipate from the eroded window of the Lower Triassic Jialingjiang Fm located on the top of the Weiyuan anticline, which is the beginning of the differential accumulation and dissipation of the natural gas in the Dengying Fm across the Sichuan Basin. During the process of the differential accumulation and dissipation, the gas below the spill point of the structural gas traps in Ziyang, Jinshi and Longnüsi–Moxi–Anpingdian–Gaoshiti areas migrated to the Weiyuan anticline along the unconformity of the Dengying Fm, and dissipated through the eroded window of the Jialingjiang Fm on the top of the Weiyuan anticline, resulting in a transformation of abnormal high pressure of gas reservoir

  12. The controlled release of simvastatin from TiO{sub 2} nanotubes to promote osteoblast differentiation and inhibit osteoclast resorption

    Energy Technology Data Exchange (ETDEWEB)

    Lai, Min, E-mail: minlai@jsnu.edu.cn [School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu 221116 (China); Jin, Ziyang; Yang, Xinyi; Wang, Huaying [School of Life Science, Jiangsu Normal University, Xuzhou, Jiangsu 221116 (China); Xu, Kui [Biomedical Engineering Center, School of Medicine, Ningbo University, Ningbo, Zhejiang 315211 (China)

    2017-02-28

    Highlights: • The TiO{sub 2} nanotube substrates filled with simvastatin were successfully coated using chitosan/gelatin multilayers. • The bio-functionalized substrates display controlled release of simvastatin in a sustained manner. • The bio-functionalized substrates have great potential for improving osteoblast differentiation. • The bio-functionalized substrates effectively inhibit osteoclast differentiation. - Abstract: The aim of this study was to fabricate a novel drug-releasing bioactive platform that has excellent potential for improving osteoblast differentiation and inhibiting osteoclast resorption. TiO{sub 2} nanotubes (TNTs) with an outer diameter of around 70 nm were prepared by an anodization method. TNTs were filled with simvastatin (SV) and then coated using chitosan/gelatin multilayers (TNT-SV-LBL). The successful fabrication of TNT-SV-LBL substrates was confirmed by field emission scanning electron microscopy (FE-SEM), atomic force microscopy (AFM), X-ray photoelectron spectroscopy (XPS) and contact angle measurement, respectively. The in vitro release behavior of simvastatin from TNT-SV-LBL substrates showed a sustained release as compared to the uncoated group. Osteoblasts adhering to TNT-SV-LBL substrates attached well and displayed significantly higher (p < 0.01) cell viability compared with the other substrates. More importantly, osteoblasts grown on TNT-SV-LBL substrates displayed a statistically significant (p < 0.01 or p < 0.05) increase in protein production levels of alkaline phosphatase (ALP), osteocalcin (OC) and mRNA expression of runt related transcription factor 2 (Runx2), ALP, collagen type I (Col I), osteopontin (OPN), OC and osteoprotegerin (OPG) compared to the other groups after 4, 7 and 14 days of culture, respectively. Additionally, multinuclear osteoclastic differentiation of RAW264.7 cells grown on TNT-SV-LBL substrates was inhibited as confirmed by tartrate-resistant acid phosphatase (TRAP) analysis. These

  13. Integrating and differentiating aspects of self-regulation: effortful control, executive functioning, and links to negative affectivity.

    Science.gov (United States)

    Bridgett, David J; Oddi, Kate B; Laake, Lauren M; Murdock, Kyle W; Bachmann, Melissa N

    2013-02-01

    Subdisciplines within psychology frequently examine self-regulation from different frameworks despite conceptually similar definitions of constructs. In the current study, similarities and differences between effortful control, based on the psychobiological model of temperament (Rothbart, Derryberry, & Posner, 1994), and executive functioning are examined and empirically tested in three studies (n = 509). Structural equation modeling indicated that effortful control and executive functioning are strongly associated and overlapping constructs (Study 1). Additionally, results indicated that effortful control is related to the executive function of updating/monitoring information in working memory, but not inhibition (Studies 2 and 3). Study 3 also demonstrates that better updating/monitoring information in working memory and better effortful control were uniquely linked to lower dispositional negative affect, whereas the executive function of low/poor inhibition was uniquely associated with an increased tendency to express negative affect. Furthermore, dispositional negative affect mediated the links between effortful control and, separately, the executive function of updating/monitoring information in working memory and the tendency to express negative affect. The theoretical implications of these findings are discussed, and a potential framework for guiding future work directed at integrating and differentiating aspects of self-regulation is suggested. PsycINFO Database Record (c) 2013 APA, all rights reserved.

  14. Resolution of low-velocity control in golf putting differentiates professionals from amateurs.

    Science.gov (United States)

    Hasegawa, Yumiko; Fujii, Keisuke; Miura, Akito; Yamamoto, Yuji

    2017-07-01

    It is difficult for humans to apply small amounts of force precisely during motor control. However, experts who have undergone extended training are thought to be able to control low-velocity movement with precision. We investigated the resolution of motor control in golf putting. A total of 10 professional and 10 high-level amateur golfers participated. Putting distances were 0.6-3.3 m, in increments of 0.3 m. We measured the impact velocity and the club-face angle at impact, and the acceleration profile of the downswing. The professionals showed significantly smaller coefficients of variation with respect to impact velocity and smaller root mean square errors in relation to acceleration profiles than did the amateurs. To examine the resolution of motor control for impact velocity, we investigated intra-participant differences in the impact velocity of the club head at two adjacent distances. We found that professionals had higher velocity precision when putting small distance intervals than did amateurs. That is, professionals had higher resolution of low-velocity control than did high-level amateurs. Our results suggest that outstanding performance at a task involves the ability to recognise small distinctions and to produce appropriate movements.

  15. Spatial control of cell attachment, proliferation, and differentiation using ion-beam induced thin films

    International Nuclear Information System (INIS)

    Tanaka, Toshiyuki; Suzuki, Yoshiaki

    2014-01-01

    Highlights: • Cellular films can be obtained ion-beam irradiation and cell culture. • Film shapes were controlled by patterned irradiation. • Cellular films were firmly attached each other. • Tubular constructions were fabricated by wide-patterned irradiation. • Nerve growth direction was controlled by varying the pattern widths. - Abstract: In this study, cellular films were fabricated by ion-beam irradiation into poly-L-lactic acid sheets and cell culture. The cellular film shapes can be controlled by pattern masks. We performed spatial cell patterning using three types of cells: fibroblasts, endothelial cells, and nerve-like cells. First, multi-layered cellular construct was fabricated by stacking fibroblast cellular films. When three cellular films were stacked and incubated, these films firmly attached to each other. Second, tubular constructs were fabricated by endothelial cell culture on linearly patterned surfaces with wide widths of 80, 120, 160, and 200 μm. The patterned cellular films were rounded into vessel-like structure. The diameters of the constructs depend upon the pattern widths. Finally, we controlled cell attachment and nerve growth of nerve-like cells by using linearly patterned surfaces with narrow widths of 10, 30, and 50 μm. Nerve growth direction was controlled by varying the pattern widths. In the case of 10 μm, the attached cells and nerve growth were straight on the patterned thin films. These cell patterning techniques are expected to have applications in tissue engineering, cell transplantation, and in vitro tissue modeling

  16. Bidirectional lipid droplet velocities are controlled by differential binding strengths of HCV core DII protein.

    Directory of Open Access Journals (Sweden)

    Rodney K Lyn

    Full Text Available Host cell lipid droplets (LD are essential in the hepatitis C virus (HCV life cycle and are targeted by the viral capsid core protein. Core-coated LDs accumulate in the perinuclear region and facilitate viral particle assembly, but it is unclear how mobility of these LDs is directed by core. Herein we used two-photon fluorescence, differential interference contrast imaging, and coherent anti-Stokes Raman scattering microscopies, to reveal novel core-mediated changes to LD dynamics. Expression of core protein's lipid binding domain II (DII-core induced slower LD speeds, but did not affect directionality of movement on microtubules. Modulating the LD binding strength of DII-core further impacted LD mobility, revealing the temporal effects of LD-bound DII-core. These results for DII-core coated LDs support a model for core-mediated LD localization that involves core slowing down the rate of movement of LDs until localization at the perinuclear region is accomplished where LD movement ceases. The guided localization of LDs by HCV core protein not only is essential to the viral life cycle but also poses an interesting target for the development of antiviral strategies against HCV.

  17. A broken promise: microbiome differential abundance methods do not control the false discovery rate.

    Science.gov (United States)

    Hawinkel, Stijn; Mattiello, Federico; Bijnens, Luc; Thas, Olivier

    2017-08-22

    High-throughput sequencing technologies allow easy characterization of the human microbiome, but the statistical methods to analyze microbiome data are still in their infancy. Differential abundance methods aim at detecting associations between the abundances of bacterial species and subject grouping factors. The results of such methods are important to identify the microbiome as a prognostic or diagnostic biomarker or to demonstrate efficacy of prodrug or antibiotic drugs. Because of a lack of benchmarking studies in the microbiome field, no consensus exists on the performance of the statistical methods. We have compared a large number of popular methods through extensive parametric and nonparametric simulation as well as real data shuffling algorithms. The results are consistent over the different approaches and all point to an alarming excess of false discoveries. This raises great doubts about the reliability of discoveries in past studies and imperils reproducibility of microbiome experiments. To further improve method benchmarking, we introduce a new simulation tool that allows to generate correlated count data following any univariate count distribution; the correlation structure may be inferred from real data. Most simulation studies discard the correlation between species, but our results indicate that this correlation can negatively affect the performance of statistical methods. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  18. Differential control of central cardiorespiratory interactions by hypercapnia and the effect of prenatal nicotine.

    Science.gov (United States)

    Huang, Zheng-Gui; Griffioen, Kathleen J S; Wang, Xin; Dergacheva, Olga; Kamendi, Harriet; Gorini, Christopher; Bouairi, Euguenia; Mendelowitz, David

    2006-01-04

    Hypercapnia evokes a strong cardiorespiratory response including gasping and a pronounced bradycardia; however, the mechanism responsible for these survival responses initiated in the brainstem is unknown. To examine the effects of hypercapnia on the central cardiorespiratory network, we used an in vitro medullary slice that allows simultaneous examination of rhythmic respiratory-related activity and inhibitory synaptic neurotransmission to cardioinhibitory vagal neurons (CVNs). Hypercapnia differentially modulated inhibitory neurotransmission to CVNs; whereas hypercapnia selectively depressed spontaneous glycinergic IPSCs in CVNs without altering respiratory-related increases in glycinergic neurotransmission, it decreased both spontaneous and inspiratory-associated GABAergic IPSCs. Because maternal smoking is the highest risk factor for sudden infant death syndrome (SIDS) and prenatal nicotine exposure is proposed to be the link between maternal smoking and SIDS, we examined the cardiorespiratory responses to hypercapnia in animals exposed to nicotine in the prenatal and perinatal period. In animals exposed to prenatal nicotine, hypercapnia evoked an exaggerated depression of GABAergic IPSCs in CVNs with no significant change in glycinergic neurotransmission. Hypercapnia altered inhibitory neurotransmission to CVNs at both presynaptic and postsynaptic sites. Although the results obtained in this study in vitro cannot be extrapolated with certainty to in vivo responses, the results of this study provide a likely neurochemical mechanism for hypercapnia-evoked bradycardia and the dysregulation of this response with exposure to prenatal nicotine, creating a higher risk for SIDS.

  19. Lhx5 controls mamillary differentiation in the developing hypothalamus of the mouse

    Directory of Open Access Journals (Sweden)

    Michael eHeide

    2015-08-01

    Full Text Available Acquisition of specific neuronal identity by individual brain nuclei is a key step in brain development. However, how the mechanisms that confer neuronal identity are integrated with upstream regional specification networks is still mysterious. Expression of Sonic hedgehog (Shh, is required for hypothalamic specification and is later downregulated by Tbx3 to allow for the differentiation of the tubero-mamillary region. In this region, the mamillary body (MBO, is a large neuronal aggregate essential for memory formation. To clarify how MBO identity is acquired after regional specification, we investigated Lhx5, a transcription factor with restricted MBO expression. We first generated a hypomorph allele of Lhx5—in homozygotes, the MBO disappears after initial specification. Intriguingly, in these mutants, Tbx3 was downregulated and the Shh expression domain abnormally extended. Microarray analysis and chromatin immunoprecipitation indicated that Lhx5 appears to be involved in Shh downregulation through Tbx3 and activates several MBO-specific regulator and effector genes. Finally, by tracing the caudal hypothalamic cell lineage we show that, in the Lhx5 mutant, at least some MBO cells are present but lack characteristic marker expression. Our work shows how the Lhx5 locus contributes to integrate regional specification pathways with downstream acquisition of neuronal identity in the MBO.

  20. Mechanism governing heme synthesis reveals a GATA factor/heme circuit that controls differentiation.

    Science.gov (United States)

    Tanimura, Nobuyuki; Miller, Eli; Igarashi, Kazuhiko; Yang, David; Burstyn, Judith N; Dewey, Colin N; Bresnick, Emery H

    2016-02-01

    Metal ion-containing macromolecules have fundamental roles in essentially all biological processes throughout the evolutionary tree. For example, iron-containing heme is a cofactor in enzyme catalysis and electron transfer and an essential hemoglobin constituent. To meet the intense demand for hemoglobin assembly in red blood cells, the cell type-specific factor GATA-1 activates transcription of Alas2, encoding the rate-limiting enzyme in heme biosynthesis, 5-aminolevulinic acid synthase-2 (ALAS-2). Using genetic editing to unravel mechanisms governing heme biosynthesis, we discovered a GATA factor- and heme-dependent circuit that establishes the erythroid cell transcriptome. CRISPR/Cas9-mediated ablation of two Alas2 intronic cis elements strongly reduces GATA-1-induced Alas2 transcription, heme biosynthesis, and surprisingly, GATA-1 regulation of other vital constituents of the erythroid cell transcriptome. Bypassing ALAS-2 function in Alas2 cis element-mutant cells by providing its catalytic product 5-aminolevulinic acid rescues heme biosynthesis and the GATA-1-dependent genetic network. Heme amplifies GATA-1 function by downregulating the heme-sensing transcriptional repressor Bach1 and via a Bach1-insensitive mechanism. Through this dual mechanism, heme and a master regulator collaborate to orchestrate a cell type-specific transcriptional program that promotes cellular differentiation. © 2015 The Authors.

  1. Differentiating between precursor and control variables when analyzing reasoned action theories.

    Science.gov (United States)

    Hennessy, Michael; Bleakley, Amy; Fishbein, Martin; Brown, Larry; Diclemente, Ralph; Romer, Daniel; Valois, Robert; Vanable, Peter A; Carey, Michael P; Salazar, Laura

    2010-02-01

    This paper highlights the distinction between precursor and control variables in the context of reasoned action theory. Here the theory is combined with structural equation modeling to demonstrate how age and past sexual behavior should be situated in a reasoned action analysis. A two wave longitudinal survey sample of African-American adolescents is analyzed where the target behavior is having vaginal sex. Results differ when age and past behavior are used as control variables and when they are correctly used as precursors. Because control variables do not appear in any form of reasoned action theory, this approach to including background variables is not correct when analyzing data sets based on the theoretical axioms of the Theory of Reasoned Action, the Theory of Planned Behavior, or the Integrative Model.

  2. Differential pathogenicity of Metarhizium anisopliae and the control of the sugarcane root spittlebug Mahanarva fimbriolata

    Directory of Open Access Journals (Sweden)

    Patricia Vieira Tiago

    2011-06-01

    Full Text Available In order to assess the effectiveness of Metarhizium anisopliae var. anisopliae (Metschnikoff Sorokin isolates in controlling the sugarcane root spittlebug Mahanarva fimbriolata (Stal (Hemiptera: Cercopidae, nine isolates obtained from a single geographical region were studied. 'Confirmed cumulative' and 'corrected cumulative' spittlebug mortality rates were measured for each of the isolates. Based on the confirmed mortality curve, the isolates URM5946, URM5951 and URM6033 were considered to be potentially the most effective in a biological control program for M. fimbriolata.

  3. siRNA nanoparticle functionalization of nanostructured scaffolds enables controlled multilineage differentiation of stem cells

    DEFF Research Database (Denmark)

    Andersen, Morten Ø; Nygaard, Jens V; Burns, Jorge S

    2010-01-01

    The creation of complex tissues and organs is the ultimate goal in tissue engineering. Engineered morphogenesis necessitates spatially controlled development of multiple cell types within a scaffold implant. We present a novel method to achieve this by adhering nanoparticles containing different ...

  4. Differential contributions of the superior and inferior parietal cortex to feedback versus feedforward control of tools.

    Science.gov (United States)

    Macuga, Kristen L; Frey, Scott H

    2014-05-15

    Damage to the superior and/or inferior parietal lobules (SPL, IPL) (Sirigu et al., 1996) or cerebellum (Grealy and Lee, 2011) can selectively disrupt motor imagery, motivating the hypothesis that these regions participate in predictive (i.e., feedforward) control. If so, then the SPL, IPL, and cerebellum should show greater activity as the demands on feedforward control increase from visually-guided execution (closed-loop) to execution without visual feedback (open-loop) to motor imagery. Using fMRI and a Fitts' reciprocal aiming task with tools directed at targets in far space, we found that the SPL and cerebellum exhibited greater activity during closed-loop control. Conversely, open-loop and imagery conditions were associated with increased activity within the IPL and prefrontal areas. These results are consistent with a superior-to-inferior gradient in the representation of feedback-to-feedforward control within the posterior parietal cortex. Additionally, the anterior SPL displayed greater activity when aiming movements were performed with a stick vs. laser pointer. This may suggest that it is involved in the remapping of far into near (reachable) space (Maravita and Iriki, 2004), or in distalization of the end-effector from hand to stick (Arbib et al., 2009). Copyright © 2014 Elsevier Inc. All rights reserved.

  5. Are Cognitive Control and Stimulus-Driven Processes Differentially Linked to Inattention and Hyperactivity in Preschoolers?

    Science.gov (United States)

    Miller, Carlin J.; Miller, Scott R.; Healey, Dione M.; Marshall, Katie; Halperin, Jeffrey M.

    2013-01-01

    Temperament and attention-deficit/hyperactivity disorder (ADHD) are both typically viewed as biologically based behavioural constructs. There is substantial overlap between ADHD symptoms and specific temperamental traits, such as effortful control, especially in young children. Recent work by Martel and colleagues (2009, 2011) suggests that…

  6. Differentiating Processes of Control and Understanding in the Early Development of Emotion and Cognition

    Science.gov (United States)

    Blankson, A. Nayena; O'Brien, Marion; Leerkes, Esther M.; Marcovitch, Stuart; Calkins, Susan D.

    2012-01-01

    In this study, we examined the hypothesis that preschoolers' performance on emotion and cognitive tasks is organized into discrete processes of control and understanding within the domains of emotion and cognition. Additionally, we examined the relations among component processes using mother report, behavioral observation, and physiological…

  7. Modeling and Control of a Manufacturing Flow Line using Partial Differential Equations

    NARCIS (Netherlands)

    Berg, van den R.A.; Lefeber, A.A.J.; Rooda, J.E.

    2008-01-01

    This brief deals with a control framework for manufacturing flow lines. For this framework, a continuous approximation model of the manufacturing system is required, which is computationally feasible and able to accurately describe the dynamics of the system (both throughput and flow time). Often

  8. Treatment of Multiply Controlled Problem Behavior with Procedural Variations of Differential Reinforcement

    Science.gov (United States)

    Neidert, Pamela L.; Iwata, Brian A.; Dozier, Claudia L.

    2005-01-01

    We describe the assessment and treatment of 2 children with autism spectrum disorder whose problem behaviors (self-injury, aggression, and disruption) were multiply controlled. Results of functional analyses indicated that the children's problem behaviors were maintained by both positive reinforcement (attention) and negative reinforcement (escape…

  9. Evidence for differential control of tibial position in perturbed unilateral stance after acute ACL rupture.

    Science.gov (United States)

    Chmielewski, T L; Ramsey, D K; Snyder-Mackler, L

    2005-01-01

    Functional outcomes in anterior cruciate ligament-deficient "potential copers" and "non-copers" may be related to their knee stabilization strategies. Therefore, the purpose of this study was to differentiate dynamic knee stabilization strategies of potential copers and non-copers through analysis of sagittal plane knee angle and tibia position during disturbed and undisturbed unilateral standing. Ten uninjured potential coper and non-coper subjects stood in unilateral stance on a platform that translated anteriorly, posteriorly and laterally. Knee angle and tibia position with reference to the femur were calculated before and after platform movement. During perturbation trials, potential copers maintained kinematics that were similar to uninjured subjects across conditions. Conversely, non-copers stood with greater knee flexion than uninjured subjects and a tibia position that was more posterior than the other groups. Both non-copers and potential copers demonstrated small changes in tibia position following platform movement, but direction of movement was not similar. The similarities between the knee kinematics of potential copers and uninjured subjects suggest that potential copers compensated well from their injury by utilizing analogous dynamic knee stabilization strategies. In comparison to the other groups, by keeping the knee in greater flexion and the tibia in a more posterior position, non-copers appear to constrain the tibia in response to a challenging task, which is consistent with a "stiffening strategy". Based on the poor functional outcomes of non-copers, a stiffening strategy does not lead to dynamic knee stability, and the strategy may increase compressive forces which could contribute to or exacerbate articular cartilage degeneration.

  10. Differentiating SCT and inattentive symptoms in ADHD using fMRI measures of cognitive control.

    Science.gov (United States)

    Fassbender, Catherine; Krafft, Cynthia E; Schweitzer, Julie B

    2015-01-01

    Attention Deficit/Hyperactivity Disorder (ADHD) is associated with different impairment profiles in the symptom domains of hyperactivity/impulsivity and/or inattention. An additional symptom domain of sluggish cognitive tempo (SCT) has also been proposed. Although there is a degree of correlation between the SCT symptom domain and inattention, it has been proposed as a distinct disorder independent of ADHD. The objective of this study was to examine the neural substrates of cue-related preparatory processes associated with SCT symptoms versus inattentive symptoms in a group of adolescents with ADHD. We also compared cue-related effects in the entire ADHD group compared with a group of typically developing (TD) peers. A modified cued flanker paradigm and fMRI examined brain activity associated with attention preparation and motor response preparation. Between group contrasts between the ADHD and TD group revealed significant hypoactivity in the ADHD group during general attention preparation in the supplementary motor area (SMA) and in the right superior parietal lobe (SPL) during response preparation. In the ADHD group, greater numbers of SCT symptoms were associated with hypoactivity in the left SPL to cues in general whereas greater numbers of inattentive symptoms were associated with greater activity in the SMA to cues that provided no information and less activity in the thalamus during response preparation. Hypoactivity in the SPL with increasing SCT symptoms may be associated with impaired reorienting or shifting of attention. Altered activity in the SMA and thalamus with increasing inattention may be associated with a general problem with response preparation, which may also reflect inefficient processing of the response preparation cue. Our results support a degree of differentiation between SCT and inattentive symptom profiles within adolescents with ADHD.

  11. Accurate control of oxygen level in cells during culture on silicone rubber membranes with application to stem cell differentiation.

    Science.gov (United States)

    Powers, Daryl E; Millman, Jeffrey R; Bonner-Weir, Susan; Rappel, Michael J; Colton, Clark K

    2010-01-01

    Oxygen level in mammalian cell culture is often controlled by placing culture vessels in humidified incubators with a defined gas phase partial pressure of oxygen (pO(2gas)). Because the cells are consuming oxygen supplied by diffusion, a difference between pO(2gas) and that experienced by the cells (pO(2cell)) arises, which is maximal when cells are cultured in vessels with little or no oxygen permeability. Here, we demonstrate theoretically that highly oxygen-permeable silicone rubber membranes can be used to control pO(2cell) during culture of cells in monolayers and aggregates much more accurately and can achieve more rapid transient response following a disturbance than on polystyrene and fluorinated ethylene-propylene copolymer membranes. Cell attachment on silicone rubber was achieved by physical adsorption of fibronectin or Matrigel. We use these membranes for the differentiation of mouse embryonic stem cells to cardiomyocytes and compare the results with culture on polystyrene or on silicone rubber on top of polystyrene. The fraction of cells that are cardiomyocyte-like increases with decreasing pO(2) only when using oxygen-permeable silicone membrane-based dishs, which contract on silicone rubber but not polystyrene. The high permeability of silicone rubber results in pO(2cell) being equal to pO(2gas) at the tissue-membrane interface. This, together with geometric information from histological sections, facilitates development of a model from which the pO(2) distribution within the resulting aggregates is computed. Silicone rubber membranes have significant advantages over polystyrene in controlling pO(2cell), and these results suggest they are a valuable tool for investigating pO(2) effects in many applications, such as stem cell differentiation. Copyright 2009 American Institute of Chemical Engineers

  12. A plasma cell differentiation quality control ablates B cell clones with biallelic Ig rearrangements and truncated Ig production.

    Science.gov (United States)

    Srour, Nivine; Chemin, Guillaume; Tinguely, Aurélien; Ashi, Mohamad Omar; Oruc, Zéliha; Péron, Sophie; Sirac, Christophe; Cogné, Michel; Delpy, Laurent

    2016-01-11

    Aberrantly rearranged immunoglobulin (Ig) alleles are frequent. They are usually considered sterile and innocuous as a result of nonsense-mediated mRNA decay. However, alternative splicing can yield internally deleted proteins from such nonproductively V(D)J-rearranged loci. We show that nonsense codons from variable (V) Igκ exons promote exon-skipping and synthesis of V domain-less κ light chains (ΔV-κLCs). Unexpectedly, such ΔV-κLCs inhibit plasma cell (PC) differentiation. Accordingly, in wild-type mice, rearrangements encoding ΔV-κLCs are rare in PCs, but frequent in B cells. Likewise, enforcing expression of ΔV-κLCs impaired PC differentiation and antibody responses without disturbing germinal center reactions. In addition, PCs expressing ΔV-κLCs synthesize low levels of Ig and are mostly found among short-lived plasmablasts. ΔV-κLCs have intrinsic toxic effects in PCs unrelated to Ig assembly, but mediated by ER stress-associated apoptosis, making PCs producing ΔV-κLCs highly sensitive to proteasome inhibitors. Altogether, these findings demonstrate a quality control checkpoint blunting terminal PC differentiation by eliminating those cells expressing nonfunctionally rearranged Igκ alleles. This truncated Ig exclusion (TIE) checkpoint ablates PC clones with ΔV-κLCs production and exacerbated ER stress response. The TIE checkpoint thus mediates selection of long-lived PCs with limited ER stress supporting high Ig secretion, but with a cost in terms of antigen-independent narrowing of the repertoire. © 2016 Srour et al.

  13. Differential Control Strategy based on an Equal Slip Rate for an All-wheel Electricdrive Underground Articulated Dumping Truck

    Directory of Open Access Journals (Sweden)

    Jin Chun

    2014-09-01

    Full Text Available A differential control strategy based on equal slip rates is introduced to improve the steering stability of an all-wheelelectric-drive underground articulated dumping truck. Steering kinematic and dynamic models of the truck are derived to describe the movement relationship and force of the driving wheels. In consideration of the difficulty of obtaining the absolute velocity for an all-wheel-drive truck, an acceleration sensor was set on a test truck, and a kalman filter was applied to obtain the actual value for the truck body. Simulation results for an equal-slip control strategy were compared with experimental results for an equal-torque control strategy. In the simulation, the four-wheel slip rate was 0.08 and the steering system of the truck was stable. The results verify that the equal-slip control strategy makes better use of the ground adhesion coefficient, is able to reasonably distribute drive power, notably reduces tire wear, and improves the use of driving power.

  14. Model-Free Adaptive Control for Unknown Nonlinear Zero-Sum Differential Game.

    Science.gov (United States)

    Zhong, Xiangnan; He, Haibo; Wang, Ding; Ni, Zhen

    2018-05-01

    In this paper, we present a new model-free globalized dual heuristic dynamic programming (GDHP) approach for the discrete-time nonlinear zero-sum game problems. First, the online learning algorithm is proposed based on the GDHP method to solve the Hamilton-Jacobi-Isaacs equation associated with optimal regulation control problem. By setting backward one step of the definition of performance index, the requirement of system dynamics, or an identifier is relaxed in the proposed method. Then, three neural networks are established to approximate the optimal saddle point feedback control law, the disturbance law, and the performance index, respectively. The explicit updating rules for these three neural networks are provided based on the data generated during the online learning along the system trajectories. The stability analysis in terms of the neural network approximation errors is discussed based on the Lyapunov approach. Finally, two simulation examples are provided to show the effectiveness of the proposed method.

  15. Loss of control over the ethanol consumption: differential transcriptional regulation in prefrontal cortex.

    Science.gov (United States)

    de Paiva Lima, Carolina; da Silva E Silva, Daniel Almeida; Damasceno, Samara; Ribeiro, Andrea Frozino; Rocha, Cristiane S; Berenguer de Matos, Alexandre H; Correia, Diego; Boerngen-Lacerda, Roseli; Brunialti Godard, Ana Lúcia

    2017-09-01

    Alcohol use disorder (AUD) is a complex multifactorial disease with heritability of ∼50% and corresponds to the state in which the body triggers a reinforcement or reward compulsive behavior due to ethanol consumption, even when faced with negative consequences. Although several studies have shown the impact of high ethanol intake on the prefrontal cortex (PFC) gene expression, few have addressed the relationship between the patterns of gene expression underlying the compulsive behaviour associated with relapsing. In this study, we used a chronic three-bottle free-choice mouse model to investigate the PFC transcriptome in three different groups of mice drinkers: 'Light drinkers' (preference for water throughout the experiment); 'Heavy drinkers' (preference for ethanol with a non-compulsive intake), and 'Inflexible drinkers' (preference for ethanol with a compulsive drinking component). Our aim was to correlate the intake patterns observed in this model with gene expression changes in the PFC, a brain region critical for the development and maintenance of alcohol addiction. We found that the Camk2a gene showed a downregulated profile only in the Inflexible when compared to the Light drinkers group, the Camk2n1 and Pkp2 genes showed an upregulated profile only in the Inflexible drinkers when compared to the Control group, and the Gja1 gene showed an upregulated profile in the Light and Inflexible drinkers when compared to the Control group. These different transcription patterns have been associated to the presence of alcohol, in the Camk2n1 and Gja1 genes; to the amount of ethanol consumed, in the Camk2a gene; and to the loss of control in the alcohol consumption, in the Pkp2 gene. Here, we provide, for the first time, the potential involvement of the Pkp2 gene in the compulsivity and loss of control over the voluntary ethanol consumption.

  16. CART neurons in the arcuate nucleus and lateral hypothalamic area exert differential controls on energy homeostasis

    Directory of Open Access Journals (Sweden)

    Jackie Lau

    2018-01-01

    Full Text Available Objective: The cocaine- and amphetamine-regulated transcript (CART codes for a pivotal neuropeptide important in the control of appetite and energy homeostasis. However, limited understanding exists for the defined effector sites underlying CART function, as discrepant effects of central CART administration have been reported. Methods: By combining Cart-cre knock-in mice with a Cart adeno-associated viral vector designed using the flip-excision switch (AAV-FLEX technology, specific reintroduction or overexpression of CART selectively in CART neurons in the arcuate nucleus (Arc and lateral hypothalamic area (LHA, respectively, was achieved. The effects on energy homeostasis control were investigated. Results: Here we show that CART neuron-specific reintroduction of CART into the Arc and LHA leads to distinct effects on energy homeostasis control. Specifically, CART reintroduction into the Arc of otherwise CART-deficient Cartcre/cre mice markedly decreased fat mass and body weight, whereas CART reintroduction into the LHA caused significant fat mass gain and lean mass loss, but overall unaltered body weight. The reduced adiposity in ArcCART;Cartcre/cre mice was associated with an increase in both energy expenditure and physical activity, along with significantly decreased Npy mRNA levels in the Arc but with no change in food consumption. Distinctively, the elevated fat mass in LHACART;Cartcre/cre mice was accompanied by diminished insulin responsiveness and glucose tolerance, greater spontaneous food intake, and reduced energy expenditure, which is consistent with the observed decrease of brown adipose tissue temperature. This is also in line with significantly reduced tyrosine hydroxylase (Th and notably increased corticotropin-releasing hormone (Crh mRNA expressions in the paraventricular nucleus (PVN. Conclusions: Taken together, these results identify catabolic and anabolic effects of CART in the Arc and LHA, respectively, demonstrating for

  17. On optimal control of a sweeping process coupled with an ordinary differential equation

    Czech Academy of Sciences Publication Activity Database

    Adam, Lukáš; Outrata, Jiří

    2014-01-01

    Roč. 19, č. 9 (2014), s. 2709-2738 ISSN 1531-3492 R&D Projects: GA ČR(CZ) GAP201/12/0671 Grant - others:GA MŠk(CZ) SVV-2013-267315 Institutional support: RVO:67985556 Keywords : optimal control * variational inequality * variational analysis * coderivative * solution map * queuing theory Subject RIV: BA - General Mathematics Impact factor: 0.768, year: 2014 http://library.utia.cas.cz/separaty/2014/MTR/adam-0434417.pdf

  18. Differential effects of absent visual feedback control on gait variability during different locomotion speeds.

    Science.gov (United States)

    Wuehr, M; Schniepp, R; Pradhan, C; Ilmberger, J; Strupp, M; Brandt, T; Jahn, K

    2013-01-01

    Healthy persons exhibit relatively small temporal and spatial gait variability when walking unimpeded. In contrast, patients with a sensory deficit (e.g., polyneuropathy) show an increased gait variability that depends on speed and is associated with an increased fall risk. The purpose of this study was to investigate the role of vision in gait stabilization by determining the effects of withdrawing visual information (eyes closed) on gait variability at different locomotion speeds. Ten healthy subjects (32.2 ± 7.9 years, 5 women) walked on a treadmill for 5-min periods at their preferred walking speed and at 20, 40, 70, and 80 % of maximal walking speed during the conditions of walking with eyes open (EO) and with eyes closed (EC). The coefficient of variation (CV) and fractal dimension (α) of the fluctuations in stride time, stride length, and base width were computed and analyzed. Withdrawing visual information increased the base width CV for all walking velocities (p < 0.001). The effects of absent visual information on CV and α of stride time and stride length were most pronounced during slow locomotion (p < 0.001) and declined during fast walking speeds. The results indicate that visual feedback control is used to stabilize the medio-lateral (i.e., base width) gait parameters at all speed sections. In contrast, sensory feedback control in the fore-aft direction (i.e., stride time and stride length) depends on speed. Sensory feedback contributes most to fore-aft gait stabilization during slow locomotion, whereas passive biomechanical mechanisms and an automated central pattern generation appear to control fast locomotion.

  19. Rapid evolution leads to differential population dynamics and top-down control in resurrected Daphnia populations.

    Science.gov (United States)

    Goitom, Eyerusalem; Kilsdonk, Laurens J; Brans, Kristien; Jansen, Mieke; Lemmens, Pieter; De Meester, Luc

    2018-01-01

    There is growing evidence of rapid genetic adaptation of natural populations to environmental change, opening the perspective that evolutionary trait change may subsequently impact ecological processes such as population dynamics, community composition, and ecosystem functioning. To study such eco-evolutionary feedbacks in natural populations, however, requires samples across time. Here, we capitalize on a resurrection ecology study that documented rapid and adaptive evolution in a natural population of the water flea Daphnia magna in response to strong changes in predation pressure by fish, and carry out a follow-up mesocosm experiment to test whether the observed genetic changes influence population dynamics and top-down control of phytoplankton. We inoculated populations of the water flea D. magna derived from three time periods of the same natural population known to have genetically adapted to changes in predation pressure in replicate mesocosms and monitored both Daphnia population densities and phytoplankton biomass in the presence and absence of fish. Our results revealed differences in population dynamics and top-down control of algae between mesocosms harboring populations from the time period before, during, and after a peak in fish predation pressure caused by human fish stocking. The differences, however, deviated from our a priori expectations. An S-map approach on time series revealed that the interactions between adults and juveniles strongly impacted the dynamics of populations and their top-down control on algae in the mesocosms, and that the strength of these interactions was modulated by rapid evolution as it occurred in nature. Our study provides an example of an evolutionary response that fundamentally alters the processes structuring population dynamics and impacts ecosystem features.

  20. Simulation, optimal control and parametric sensitivity analysis of a molten carbonate fuel cell using a partial differential algebraic dynamic equation system; Simulation, Optimale Steuerung und Sensitivitaetsanalyse einer Schmelzkarbonat-Brennstoffzelle mithilfe eines partiellen differential-algebraischen dynamischen Gleichungssystems

    Energy Technology Data Exchange (ETDEWEB)

    Sternberg, K

    2007-02-08

    Molten carbonate fuel cells (MCFCs) allow an efficient and environmentally friendly energy production by converting the chemical energy contained in the fuel gas in virtue of electro-chemical reactions. In order to predict the effect of the electro-chemical reactions and to control the dynamical behavior of the fuel cell a mathematical model has to be found. The molten carbonate fuel cell (MCFC) can indeed be described by a highly complex,large scale, semi-linear system of partial differential algebraic equations. This system includes a reaction-diffusion-equation of parabolic type, several reaction-transport-equations of hyperbolic type, several ordinary differential equations and finally a system of integro-differential algebraic equations which describes the nonlinear non-standard boundary conditions for the entire partial differential algebraic equation system (PDAE-system). The existence of an analytical or the computability of a numerical solution for this high-dimensional PDAE-system depends on the kind of the differential equations and their special characteristics. Apart from theoretical investigations, the real process has to be controlled, more precisely optimally controlled. Hence, on the basis of the PDAE-system an optimal control problem is set up, whose analytical and numerical solvability is closely linked to the solvability of the PDAE-system. Moreover the solution of that optimal control problem is made more difficult by inaccuracies in the underlying database, which does not supply sufficiently accurate values for the model parameters. Therefore the optimal control problem must also be investigated with respect to small disturbances of model parameters. The aim of this work is to analyze the relevant dynamic behavior of MCFCs and to develop concepts for their optimal process control. Therefore this work is concerned with the simulation, the optimal control and the sensitivity analysis of a mathematical model for MCDCs, which can be characterized

  1. Differential effects of mental stress on plasma homovanillic acid in schizophrenia and normal controls.

    Science.gov (United States)

    Sumiyoshi, T; Saitoh, O; Yotsutsuji, T; Itoh, H; Kurokawa, K; Kurachi, M

    1999-04-01

    We previously reported that mental stress by Kraepelin's arithmetic test decreases plasma homovanillic acid (pHVA) levels in psychiatrically normal healthy human subjects. The present study was undertaken to determine whether this pattern of changes in pHVA concentrations resulting from mental stress is altered in patients with schizophrenia. Fourteen male patients with schizophrenia including those under ongoing neuroleptic treatment and 14 normal male volunteers participated in the study. Following overnight fast and restricted physical activity, the subjects performed Kraepelin's arithmetic test for 30 minutes. Plasma samples were collected immediately before and after the test for measurement of pHVA levels. A significant diagnosis by Kraepelin's test effect was observed due to a decrease in pHVA levels by the Kraepelin test in control subjects but not in patients with schizophrenia. Changes in pHVA levels during the Kraepelin test positively correlated with pre-test pHVA levels in control subjects, while this correlation was not observed in patients with schizophrenia. These results may be further support for the presence of a dopamine-dependent restitutive system in the brain. The absence of response of pHVA levels to mental stress in patients with schizophrenia may indicate that the dopamine restitutive system in these patients is disrupted or already down-regulated, as previously predicted.

  2. Asymptotic analysis and optimal control of an integro-differential system modelling healthy and cancer cells exposed to chemotherapy

    KAUST Repository

    Pouchol, Camille

    2017-10-27

    We consider a system of two coupled integro-differential equations modelling populations of healthy and cancer cells under chemotherapy. Both populations are structured by a phenotypic variable, representing their level of resistance to the treatment. We analyse the asymptotic behaviour of the model under constant infusion of drugs. By designing an appropriate Lyapunov function, we prove that both cell densities converge to Dirac masses. We then define an optimal control problem, by considering all possible infusion protocols and minimising the number of cancer cells over a prescribed time frame. We provide a quasi-optimal strategy and prove that it solves this problem for large final times. For this modelling framework, we illustrate our results with numerical simulations, and compare our optimal strategy with periodic treatment schedules.

  3. Implicit versus explicit measures of self-concept of self-control and their differential predictive power for spontaneous trait-relevant behaviors

    NARCIS (Netherlands)

    Huntjens, Rafaële J C; Rijkeboer, Marleen M; Krakau, Andrej; de Jong, Peter J

    BACKGROUND AND OBJECTIVES: Low trait self-control constitutes a core criterion in various psychiatric disorders. Personality traits such as low self-control are mostly indexed by self-report measures. However, several theorists emphasized the importance of differentiating between explicit and

  4. Implicit versus explicit measures of self-concept of self-control and their differential predictive power for spontaneous trait-relevant behaviors

    NARCIS (Netherlands)

    Huntjens, Rafaele J. C.; Rijkeboer, Marleen M.; Krakau, Andrej; de Jong, Peter J.

    BACKGROUND AND OBJECTIVES: Low trait self-control constitutes a core criterion in various psychiatric disorders. Personality traits such as low self-control are mostly indexed by self-report measures. However, several theorists emphasized the importance of differentiating between explicit and

  5. Differentiating Motivational from Affective Influence of Performance-contingent Reward on Cognitive Control: The Wanting Component Enhances Both Proactive and Reactive Control.

    Science.gov (United States)

    Chaillou, Anne-Clémence; Giersch, Anne; Hoonakker, Marc; Capa, Rémi L; Bonnefond, Anne

    2017-04-01

    Positive affect strongly modulates goal-directed behaviors and cognitive control mechanisms. It often results from the presence of a pleasant stimulus in the environment, whether that stimulus appears unpredictably or as a consequence of a particular behavior. The influence of positive affect linked to a random pleasant stimulus differs from the influence of positive affect resulting from performance-contingent pleasant stimuli. However, the mechanisms by which the performance contingency of pleasant stimuli modulates the influence of positive affect on cognitive control mechanisms have not been elucidated. Here, we tested the hypothesis that these differentiated effects are the consequence of the activation of the motivational "wanting" component specifically under performance contingency conditions. To that end, we directly compared the effects on cognitive control of pleasant stimuli (a monetary reward) attributed in a performance contingent manner, and of random pleasant stimuli (positive picture) not related to performance, during an AX-CPT task. Both proactive and reactive modes of control were increased specifically by performance contingency, as reflected by faster reaction times and larger amplitude of the CNV and P3a components. Our findings advance our understanding of the respective effects of affect and motivation, which is of special interest regarding alterations of emotion-motivation interaction found in several psychopathological disorders. Copyright © 2017 Elsevier B.V. All rights reserved.

  6. eEF1A Controls ascospore differentiation through elevated accuracy, but controls longevity and fruiting body formation through another mechanism in Podospora anserina.

    Science.gov (United States)

    Silar, P; Lalucque, H; Haedens, V; Zickler, D; Picard, M

    2001-01-01

    Antisuppressor mutations in the eEF1A gene of Podospora anserina were previously shown to impair ascospore formation, to drastically increase life span, and to permit the development of the Crippled Growth degenerative process. Here, we show that eEF1A controls ascospore formation through accuracy level maintenance. Examination of antisuppressor mutant perithecia reveals two main cytological defects, mislocalization of spindle and nuclei and nuclear death. Antisuppression levels are shown to be highly dependent upon both the mutation site and the suppressor used, precluding any correlation between antisuppression efficiency and severity of the sporulation impairment. Nevertheless, severity of ascospore differentiation defect is correlated with resistance to paromomycin. We also show that eEF1A controls fruiting body formation and longevity through a mechanism(s) different from accuracy control. In vivo, GFP tagging of the protein in a way that partly retains its function confirmed earlier cytological observation; i.e., this factor is mainly diffuse within the cytosol, but may transiently accumulate within nuclei or in defined regions of the cytoplasm. These data emphasize the fact that the translation apparatus exerts a global regulatory control over cell physiology and that eEF1A is one of the key factors involved in this monitoring. PMID:11514440

  7. Differential effects of phenylephrine and norepinephrine on peripheral tissue oxygenation during general anaesthesia : A randomised controlled trial

    NARCIS (Netherlands)

    Poterman, Marieke; Vos, Jaap Jan; Vereecke, Hugo E. M.; Struys, Michel M. R. F.; Vanoverschelde, Henk; Scheeren, Thomas W. L.; Kalmar, Alain F.

    BACKGROUND Phenylephrine and norepinephrine are two vasopressors commonly used to counteract anaesthesia-induced hypotension. Their dissimilar working mechanisms may differentially affect the macro and microcirculation, and ultimately tissue oxygenation. OBJECTIVES We investigated the differential

  8. Habituation and adaptation of the vestibuloocular reflex: a model of differential control by the vestibulocerebellum

    Science.gov (United States)

    Cohen, H.; Cohen, B.; Raphan, T.; Waespe, W.

    1992-01-01

    element that controls rapid changes in eye velocity in the VOR is separate from that which couples afferent input to velocity storage. Nodulouvulectomy caused a prompt and permanent loss of habituation, returning VOR time constants to initial values. VOR gain adaptation, which is lost after flocculectomy, was unaffected by nodulouvulectomy. Flocculectomy did not alter habituation of the VOR or of OKAN. Using a simplified model of the VOR, the decrease in the duration of vestibular nystagmus due to habituation was related to a decrement in the dominant time constant of the velocity storage integrator (1/h0).(ABSTRACT TRUNCATED AT 400 WORDS).

  9. Preliminary panoramic study of river calm muscle using neodymium:yttrium-aluminum-garnet (Nd: YAG) laser-induced breakdown spectroscopy (LIBS)

    Science.gov (United States)

    Idris, N.; Lahna, K.; Usmawanda, T. N.; Herman; Ramli, M.; Hedwig, R.; Marpaung, A. M.; Kurniawan, K. H.

    2018-04-01

    A wide coverage spectral investigation on the muscle of river calm sample has been carried out using laser-induced breakdown spectroscopy for examining the overall profile of the emission spectra from the produced plasma. The basic apparatus of LIBS system used is a Nd-YAG laser and wide coverage optical multichannel analyzer (OMA) system. The river clam samples used is collected from Panga River in Aceh Jaya Regency, Aceh, Indonesia up streaming in a mountain of Gunong Ujeun, which is used as a location of the intensive traditional mining activity. Assuming that heavy metal accumulated in the clam muscle, LIBS experiments were carried out on the muscle of the calm. The sample used was fresh muscle sliced and attached to a copper plate. Plasma was generated by focusing the laser beam on the sample surface under air surrounding gas at 1 atmosphere. It is found that there are only major elements of host organic, namely C, H, O, N and the minor element of salts can be detected from fresh the clam sample when using a high pulse laser energy under air surrounding at high pressure of 1 atmosphere. There is no emission lines from any metal can be detected. Several experimental parameters were explored to study the panoramic dynamic of the emission spectra. It is found that the lower energy and the lower pressure is better for obtaining better emission spectra showing the possibility for determination of the analyte.

  10. Differential controls on soil carbon density and mineralization among contrasting forest types in a temperate forest ecosystem

    Science.gov (United States)

    You, Ye-Ming; Wang, Juan; Sun, Xiao-Lu; Tang, Zuo-Xin; Zhou, Zhi-Yong; Sun, Osbert Jianxin

    2016-01-01

    Understanding the controls on soil carbon dynamics is crucial for modeling responses of ecosystem carbon balance to global change, yet few studies provide explicit knowledge on the direct and indirect effects of forest stands on soil carbon via microbial processes. We investigated tree species, soil, and site factors in relation to soil carbon density and mineralization in a temperate forest of central China. We found that soil microbial biomass and community structure, extracellular enzyme activities, and most of the site factors studied varied significantly across contrasting forest types, and that the associations between activities of soil extracellular enzymes and microbial community structure appeared to be weak and inconsistent across forest types, implicating complex mechanisms in the microbial regulation of soil carbon metabolism in relation to tree species. Overall, variations in soil carbon density and mineralization are predominantly accounted for by shared effects of tree species, soil, microclimate, and microbial traits rather than the individual effects of the four categories of factors. Our findings point to differential controls on soil carbon density and mineralization among contrasting forest types and highlight the challenge to incorporate microbial processes for constraining soil carbon dynamics in global carbon cycle models. PMID:26925871

  11. Control entropy identifies differential changes in complexity of walking and running gait patterns with increasing speed in highly trained runners.

    Science.gov (United States)

    McGregor, Stephen J; Busa, Michael A; Skufca, Joseph; Yaggie, James A; Bollt, Erik M

    2009-06-01

    Regularity statistics have been previously applied to walking gait measures in the hope of gaining insight into the complexity of gait under different conditions and in different populations. Traditional regularity statistics are subject to the requirement of stationarity, a limitation for examining changes in complexity under dynamic conditions such as exhaustive exercise. Using a novel measure, control entropy (CE), applied to triaxial continuous accelerometry, we report changes in complexity of walking and running during increasing speeds up to exhaustion in highly trained runners. We further apply Karhunen-Loeve analysis in a new and novel way to the patterns of CE responses in each of the three axes to identify dominant modes of CE responses in the vertical, mediolateral, and anterior/posterior planes. The differential CE responses observed between the different axes in this select population provide insight into the constraints of walking and running in those who may have optimized locomotion. Future comparisons between athletes, healthy untrained, and clinical populations using this approach may help elucidate differences between optimized and diseased locomotor control.

  12. Recreational Physical Activity and Differentiated Thyroid Cancer Risk: A Pooled Analysis of Two Case-Control Studies

    Science.gov (United States)

    Xhaard, Constance; Lence-Anta, Juan J.; Ren, Yan; Borson-Chazot, Françoise; Sassolas, Geneviève; Schvartz, Claire; Colonna, Marc; Lacour, Brigitte; Danzon, Arlette; Velten, Michel; Clero, Enora; Maillard, Stéphane; Marrer, Emilie; Bailly, Laurent; Mariné Barjoan, Eugènia; Schlumberger, Martin; Orgiazzi, Jacques; Adjadj, Elisabeth; Pereda, Celia M.; Turcios, Silvia; Velasco, Milagros; Chappe, Mae; Infante, Idalmis; Bustillo, Marlene; García, Anabel; Salazar, Sirced; Rodriguez, Regla; Benadjaoud, Mohamed Amine; Ortiz, Rosa M.; Rubino, Carole; de Vathaire, Florent

    2016-01-01

    Purpose Physical activity has been hypothesized to influence cancer occurrence through several mechanisms. To date, its relation with thyroid cancer risk has been examined in relatively few studies. We pooled 2 case-control studies conducted in Cuba and Eastern France to assess the relationship between self-reported practice of recreational physical activity since childhood and thyroid cancer risk. Methods This pooled study included 1,008 cases of differentiated thyroid cancer (DTC) matched with 1,088 controls (age range 9-35 and 17-60 years in the French and Cuban studies, respectively). Risk factors associated with the practice of recreational physical activity were estimated using OR and 95% CI. Logistic regressions were stratified by age class, country, and gender and were adjusted for ethnic group, level of education, number of pregnancies for women, height, BMI, and smoking status. Results Overall, the risk of thyroid cancer was slightly reduced among subjects who reported recreational physical activity (OR = 0.8; 95% CI 0.5-1.0). The weekly frequency (i.e. h/week) seems to be more relevant than the duration (years). Conclusion Long-term recreational physical activity, practiced since childhood, may reduce the DTC risk. However, the mechanisms whereby the DTC risk decreases are not yet entirely clear. PMID:27493888

  13. Functional Conservation of the Glide/Gcm Regulatory Network Controlling Glia, Hemocyte, and Tendon Cell Differentiation in Drosophila

    Science.gov (United States)

    Cattenoz, Pierre B.; Popkova, Anna; Southall, Tony D.; Aiello, Giuseppe; Brand, Andrea H.; Giangrande, Angela

    2016-01-01

    High-throughput screens allow us to understand how transcription factors trigger developmental processes, including cell specification. A major challenge is identification of their binding sites because feedback loops and homeostatic interactions may mask the direct impact of those factors in transcriptome analyses. Moreover, this approach dissects the downstream signaling cascades and facilitates identification of conserved transcriptional programs. Here we show the results and the validation of a DNA adenine methyltransferase identification (DamID) genome-wide screen that identifies the direct targets of Glide/Gcm, a potent transcription factor that controls glia, hemocyte, and tendon cell differentiation in Drosophila. The screen identifies many genes that had not been previously associated with Glide/Gcm and highlights three major signaling pathways interacting with Glide/Gcm: Notch, Hedgehog, and JAK/STAT, which all involve feedback loops. Furthermore, the screen identifies effector molecules that are necessary for cell-cell interactions during late developmental processes and/or in ontogeny. Typically, immunoglobulin (Ig) domain–containing proteins control cell adhesion and axonal navigation. This shows that early and transiently expressed fate determinants not only control other transcription factors that, in turn, implement a specific developmental program but also directly affect late developmental events and cell function. Finally, while the mammalian genome contains two orthologous Gcm genes, their function has been demonstrated in vertebrate-specific tissues, placenta, and parathyroid glands, begging questions on the evolutionary conservation of the Gcm cascade in higher organisms. Here we provide the first evidence for the conservation of Gcm direct targets in humans. In sum, this work uncovers novel aspects of cell specification and sets the basis for further understanding of the role of conserved Gcm gene regulatory cascades. PMID:26567182

  14. Optimal Control Method of Parabolic Partial Differential Equations and Its Application to Heat Transfer Model in Continuous Cast Secondary Cooling Zone

    Directory of Open Access Journals (Sweden)

    Yuan Wang

    2015-01-01

    Full Text Available Our work is devoted to a class of optimal control problems of parabolic partial differential equations. Because of the partial differential equations constraints, it is rather difficult to solve the optimization problem. The gradient of the cost function can be found by the adjoint problem approach. Based on the adjoint problem approach, the gradient of cost function is proved to be Lipschitz continuous. An improved conjugate method is applied to solve this optimization problem and this algorithm is proved to be convergent. This method is applied to set-point values in continuous cast secondary cooling zone. Based on the real data in a plant, the simulation experiments show that the method can ensure the steel billet quality. From these experiment results, it is concluded that the improved conjugate gradient algorithm is convergent and the method is effective in optimal control problem of partial differential equations.

  15. Deletions of a differentially methylated CpG island at SNRPN define a putative imprinting control region

    Energy Technology Data Exchange (ETDEWEB)

    Sutcliffe, J.S.,; Nakao, M.; Beaudet, A.L. [Baylor College of Medicine, Houston, TX (United States)] [and others

    1994-09-01

    Prader-Willi syndrome (PWS) and Angelman syndrome (AS) are associated with paternal and maternal deficiencies, respectively, of gene expression within human chromosome 15q11-q13, and are caused by deletion, uniparental disomy, or other mutations. Four transcripts designated PAR-5, PAR-7, PAR-1 and PAR-4 were isolated and localized to a region within 300 kb telomeric to the gene encoding small nuclear ribonucleoprotein-associated polypeptide N (SNRPN). Analysis of the transcripts in cultured fibroblasts and lymphoblasts from deletion patients demonstrated that SNRPN, PAR-5 and PAR-1 are expressed exclusively from the paternal chromosome, defining an imprinted domain that spans at least 200 kb. All three imprinted transcripts were absent in cells from three PWS patients (one pair of sibs and one sporadic case) with small deletions that involve a differentially methylated CpG island containing a previously undescribed 5{prime} untranslated exon ({alpha}) of SNRPN. Methylation of the CpG island is specific for the maternal chromosome consistent with paternal expression of the imprinted domain. One deletion, which is benign when maternally transmitted, extends upstream <30 kb from the CpG island, and is associated with altered methylation centromeric to SNRPN, and loss of transcription telomeric to SNRPN, implying the presence of an imprinting control region around the CpG island containing exon {alpha}.

  16. Differentiation of organic and non-organic winter wheat cultivars from a controlled field trial by crystallization patterns.

    Science.gov (United States)

    Kahl, Johannes; Busscher, Nicolaas; Mergardt, Gaby; Mäder, Paul; Torp, Torfinn; Ploeger, Angelika

    2015-01-01

    There is a need for authentication tools in order to verify the existing certification system. Recently, markers for analytical authentication of organic products were evaluated. Herein, crystallization with additives was described as an interesting fingerprint approach which needs further evidence, based on a standardized method and well-documented sample origin. The fingerprint of wheat cultivars from a controlled field trial is generated from structure analysis variables of crystal patterns. Method performance was tested on factors such as crystallization chamber, day of experiment and region of interest of the patterns. Two different organic treatments and two different treatments of the non-organic regime can be grouped together in each of three consecutive seasons. When the k-nearest-neighbor classification method was applied, approximately 84% of Runal samples and 95% of Titlis samples were classified correctly into organic and non-organic origin using cross-validation. Crystallization with additive offers an interesting complementary fingerprint method for organic wheat samples. When the method is applied to winter wheat from the DOK trial, organic and non-organic treated samples can be differentiated significantly based on pattern recognition. Therefore crystallization with additives seems to be a promising tool in organic wheat authentication. © 2014 Society of Chemical Industry.

  17. Mosquito control pesticides and sea surface temperatures have differential effects on the survival and oxidative stress response of coral larvae.

    Science.gov (United States)

    Ross, Cliff; Olsen, Kevin; Henry, Michael; Pierce, Richard

    2015-04-01

    The declining health of coral reefs is intensifying worldwide at an alarming rate due to the combined effects of land-based sources of pollution and climate change. Despite the persistent use of mosquito control pesticides in populated coastal areas, studies examining the survival and physiological impacts of early life-history stages of non-targeted marine organisms are limited. In order to better understand the combined effects of mosquito pesticides and rising sea surface temperatures, we exposed larvae from the coral Porites astreoides to selected concentrations of two major mosquito pesticide ingredients, naled and permethrin, and seawater elevated +3.5 °C. Following 18-20 h of exposure, larvae exposed to naled concentrations of 2.96 µg L(-1) or greater had significantly reduced survivorship compared to controls. These effects were not detected in the presence of permethrin or elevated temperature. Furthermore, larval settlement, post-settlement survival and zooxanthellae density were not impacted by any treatment. To evaluate the sub-lethal stress response of larvae, several oxidative stress endpoints were utilized. Biomarker responses to pesticide exposure were variable and contingent upon pesticide type as well as the specific biomarker being employed. In some cases, such as with protein carbonylation and catalase gene expression, the effects of naled exposure and temperature were interactive. In other cases pesticide exposure failed to induce any sub-lethal stress response. Overall, these results demonstrate that P. astreoides larvae have a moderate degree of resistance against short-term exposure to ecologically relevant concentrations of pesticides even in the presence of elevated temperature. In addition, this work highlights the importance of considering the complexity and differential responses encountered when examining the impacts of combined stressors that occur on varying spatial scales.

  18. Metabolic and cardiovascular risk in patients with a history of differentiated thyroid carcinoma: A case-controlled cohort study.

    Science.gov (United States)

    Giusti, Massimo; Mortara, Lorenzo; Degrandi, Roberta; Cecoli, Francesca; Mussap, Michele; Rodriguez, Guido; Ferone, Diego; Minuto, Francesco

    2008-09-29

    Hyperthyroidism seems to increase metabolic and cardiovascular risk, while the effects of sub-clinical hyperthyroidism are controversial. We evaluated metabolic and cardiovascular parameters in differentiated thyroid carcinoma (DTC) patients with suppressed thyrotropin (TSH) due to levo-thyroxine (L-T4) therapy. We studied DTC patients and, as a control group, patients with a history of surgery for non-malignant thyroid pathology. Significantly higher insulin and lower HDL-cholesterol levels were recorded in DTC subjects. In both groups, insulin levels were significantly related with body mass index (BMI) but not with age or L-T4 dosage. In DTC patients, a significant negative correlation was seen between HDL-cholesterol and BMI or L-T4 dosage. In both groups, intima-media thickness (IMT) correlated positively with age, BMI, glucose levels and systolic blood pressure. In DTC patients, increased IMT was significantly correlated with glycated hemoglobin (HbA1c), cholesterol and triglycerides. In DTC patients, C-reactive protein correlated positively with insulin, insulin resistance, triglycerides and systolic blood pressure, and negatively with HDL-cholesterol. In both DTC and control subjects, fibrinogen correlated positively with age, BMI, increased IMT, HbA1c and systolic blood pressure. In DTC subjects, plasma fibrinogen concentrations correlated positively with insulin resistance, cholesterol and LDL-cholesterol, and negatively with TSH levels. Our data confirm that the favorable evolution of DTC can be impaired by a high incidence of abnormal metabolic and cardiovascular data that are, at least in part, related to L-T4 therapy. These findings underline the need for adequate L-T4 titration.

  19. Metabolic and cardiovascular risk in patients with a history of differentiated thyroid carcinoma: A case-controlled cohort study

    Directory of Open Access Journals (Sweden)

    Giusti Massimo

    2008-09-01

    Full Text Available Abstract Hyperthyroidism seems to increase metabolic and cardiovascular risk, while the effects of sub-clinical hyperthyroidism are controversial. We evaluated metabolic and cardiovascular parameters in differentiated thyroid carcinoma (DTC patients with suppressed thyrotropin (TSH due to levo-thyroxine (L-T4 therapy. We studied DTC patients and, as a control group, patients with a history of surgery for non-malignant thyroid pathology. Significantly higher insulin and lower HDL-cholesterol levels were recorded in DTC subjects. In both groups, insulin levels were significantly related with body mass index (BMI but not with age or L-T4 dosage. In DTC patients, a significant negative correlation was seen between HDL-cholesterol and BMI or L-T4 dosage. In both groups, intima-media thickness (IMT correlated positively with age, BMI, glucose levels and systolic blood pressure. In DTC patients, increased IMT was significantly correlated with glycated hemoglobin (HbA1c, cholesterol and triglycerides. In DTC patients, C-reactive protein correlated positively with insulin, insulin resistance, triglycerides and systolic blood pressure, and negatively with HDL-cholesterol. In both DTC and control subjects, fibrinogen correlated positively with age, BMI, increased IMT, HbA1c and systolic blood pressure. In DTC subjects, plasma fibrinogen concentrations correlated positively with insulin resistance, cholesterol and LDL-cholesterol, and negatively with TSH levels. Our data confirm that the favorable evolution of DTC can be impaired by a high incidence of abnormal metabolic and cardiovascular data that are, at least in part, related to L-T4 therapy. These findings underline the need for adequate L-T4 titration.

  20. When drugs in the same controlled substance schedule differ in real-world abuse, should they be differentiated in labeling?

    Science.gov (United States)

    Dasgupta, Nabarun; Henningfield, Jack E; Ertischek, Michelle D; Schnoll, Sidney H

    2011-12-01

    The prescription drugs regulated in the most restrictive controlled substance schedule for those with an approved therapeutic use vary widely in their real world risk of abuse and harm. Opioid analgesics have the highest rates of abuse, overdose death, drug abuse treatment needs and societal costs in comparison to other Schedule II drugs. Stimulants for attention-deficit/hyperactivity disorders (ADHD) account for substantially lower rates of abuse, harm, and public health impact. The scheduling of drugs is determined by the World Health Organization, the United States Food and Drug Administration, and other regulatory agencies, through a quasi-public process that relies heavily on pre-marketing studies that are conducted in highly controlled clinical settings. We propose that it is increasingly in the interest of science-based regulation and public health to recognize and communicate differences among drugs based on their real-world abuse and public health harm using surveillance data. Appropriate differentiation through labeling of drugs that will likely remain in the same schedule could provide powerful incentives for drug development and research, would aid prescriber/patient decision making by informing them of real differences across drugs within a schedule, and may also contribute to public health efforts to reduce drug abuse. There are risks of course, that include inadvertent perceptions that drugs labeled to be lower in risk are not taken as seriously as others in the same category. Challenges such as these, however, can be overcome and should not serve as barriers to objective communications regarding a drug's actual risks. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  1. Uhrf1 controls the self-renewal versus differentiation of hematopoietic stem cells by epigenetically regulating the cell-division modes.

    Science.gov (United States)

    Zhao, Jingyao; Chen, Xufeng; Song, Guangrong; Zhang, Jiali; Liu, Haifeng; Liu, Xiaolong

    2017-01-10

    Hematopoietic stem cells (HSCs) are able to both self-renew and differentiate. However, how individual HSC makes the decision between self-renewal and differentiation remains largely unknown. Here we report that ablation of the key epigenetic regulator Uhrf1 in the hematopoietic system depletes the HSC pool, leading to hematopoietic failure and lethality. Uhrf1-deficient HSCs display normal survival and proliferation, yet undergo erythroid-biased differentiation at the expense of self-renewal capacity. Notably, Uhrf1 is required for the establishment of DNA methylation patterns of erythroid-specific genes during HSC division. The expression of these genes is enhanced in the absence of Uhrf1, which disrupts the HSC-division modes by promoting the symmetric differentiation and suppressing the symmetric self-renewal. Moreover, overexpression of one of the up-regulated genes, Gata1, in HSCs is sufficient to phenocopy Uhrf1-deficient HSCs, which show impaired HSC symmetric self-renewal and increased differentiation commitment. Taken together, our findings suggest that Uhrf1 controls the self-renewal versus differentiation of HSC through epigenetically regulating the cell-division modes, thus providing unique insights into the relationship among Uhrf1-mediated DNA methylation, cell-division mode, and HSC fate decision.

  2. CD4+CD25+ regulatory T cells control CD8+ T-cell effector differentiation by modulating IL-2 homeostasis

    Science.gov (United States)

    McNally, Alice; Hill, Geoffrey R.; Sparwasser, Tim; Thomas, Ranjeny; Steptoe, Raymond J.

    2011-01-01

    CD4+CD25+ regulatory T cells (Treg) play a crucial role in the regulation of immune responses. Although many mechanisms of Treg suppression in vitro have been described, the mechanisms by which Treg modulate CD8+ T cell differentiation and effector function in vivo are more poorly defined. It has been proposed, in many instances, that modulation of cytokine homeostasis could be an important mechanism by which Treg regulate adaptive immunity; however, direct experimental evidence is sparse. Here we demonstrate that CD4+CD25+ Treg, by critically regulating IL-2 homeostasis, modulate CD8+ T-cell effector differentiation. Expansion and effector differentiation of CD8+ T cells is promoted by autocrine IL-2 but, by competing for IL-2, Treg limit CD8+ effector differentiation. Furthermore, a regulatory loop exists between Treg and CD8+ effector T cells, where IL-2 produced during CD8+ T-cell effector differentiation promotes Treg expansion. PMID:21502514

  3. Differential benefits of amoxicillin-metronidazole in different phases of periodontal therapy in a randomized controlled crossover clinical trial.

    Science.gov (United States)

    Mombelli, Andrea; Almaghlouth, Adnan; Cionca, Norbert; Courvoisier, Delphine S; Giannopoulou, Catherine

    2015-03-01

    The specific advantage of administering systemic antibiotics during initial, non-surgical therapy or in the context of periodontal surgery is unclear. This study assesses the differential outcomes of periodontal therapy supplemented with amoxicillin-metronidazole during either the non-surgical or the surgical treatment phase. This is a single-center, randomized placebo-controlled crossover clinical trial with a 1-year follow-up. Eighty participants with Aggregatibacter actinomycetemcomitans-associated moderate to advanced periodontitis were randomized into two treatment groups: group A, antibiotics (500 mg metronidazole plus 375 mg amoxicillin three times per day for 7 days) during the first, non-surgical phase of periodontal therapy (T1) and placebo during the second, surgical phase (T2); and group B, placebo during T1 and antibiotics during T2. The number of sites with probing depth (PD) >4 mm and bleeding on probing (BOP) per patient was the primary outcome. A total of 11,212 sites were clinically monitored on 1,870 teeth. T1 with antibiotics decreased the number of sites with PD >4 mm and BOP per patient significantly more than without (group A: from 34.5 to 5.7, 84%; group B: from 28.7 to 8.7, 70%; P antibiotics, but only eight treated with placebo, achieved a 10-fold reduction of diseased sites (P = 0.007). Consequently, fewer patients of group A needed additional therapy, the mean number of surgical interventions was lower, and treatment time in T2 was shorter. Six months after T2, the mean number of residual pockets (group A: 2.8 ± 5.2; group B: 2.2 ± 5.0) was not significantly different and was sustained over 12 months in both groups. Giving the antibiotics during T1 or T2 yielded similar long-term outcomes, but antibiotics in T1 resolved the disease quicker and thus reduced the need for additional surgical intervention.

  4. Adaptive super-twisting sliding mode control for a three-phase single-stage grid-connected differential boost inverter based photovoltaic system.

    Science.gov (United States)

    Pati, Akshaya K; Sahoo, N C

    2017-07-01

    This paper presents an adaptive super-twisting sliding mode control (STC) along with double-loop control for voltage tracking performance of three-phase differential boost inverter and DC-link capacitor voltage regulation in grid-connected PV system. The effectiveness of the proposed control strategies are demonstrated under realistic scenarios such as variations in solar insolation, load power demand, grid voltage, and transition from grid-connected to standalone mode etc. Additional supplementary power quality control functions such as harmonic compensation, and reactive power management are also investigated with the proposed control strategy. The results are compared with conventional proportional-integral controller, and PWM sliding mode controller. The system performance is evaluated in simulation and in real-time. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

  5. Diffuse reflectance spectroscopy for optical soft tissue differentiation as remote feedback control for tissue-specific laser surgery.

    Science.gov (United States)

    Stelzle, Florian; Tangermann-Gerk, Katja; Adler, Werner; Zam, Azhar; Schmidt, Michael; Douplik, Alexandre; Nkenke, Emeka

    2010-04-01

    Laser surgery does not provide haptic feedback for operating layer-by-layer and thereby preserving vulnerable anatomical structures like nerve tissue or blood vessels. Diffuse reflectance spectra can facilitate remote optical tissue differentiation. It is the aim of the study to use this technique on soft tissue samples, to set a technological basis for a remote optical feedback system for tissue-specific laser surgery. Diffuse reflectance spectra (wavelength range: 350-650 nm) of ex vivo types of soft tissue (a total of 10,800 spectra) of the midfacial region of domestic pigs were remotely measured under reduced environmental light conditions and analyzed in order to differentiate between skin, mucosa, muscle, subcutaneous fat, and nerve tissue. We performed a principal components (PC) analysis (PCA) to reduce the number of variables. Linear discriminant analysis (LDA) was utilized for classification. For the tissue differentiation, we calculated the specificity and sensitivity by receiver operating characteristic (ROC) analysis and the area under curve (AUC). Six PCs were found to be adequate for tissue differentiation with diffuse reflectance spectra using LDA. All of the types of soft tissue could be differentiated with high specificity and sensitivity. Only the tissue pairs nervous tissue/fatty tissue and nervous tissue/mucosa showed a decline of differentiation due to bio-structural similarity. However, both of these tissue pairs could still be differentiated with a specificity and sensitivity of more than 90%. Analyzing diffuse reflectance spectroscopy with PCA and LDA allows for remote differentiation of biological tissue. Considering the limitations of the ex vivo conditions, the obtained results are promising and set a basis for the further development of a feedback system for tissue-specific laser surgery. (c) 2010 Wiley-Liss, Inc.

  6. Dual-specificity phosphatase 10 controls brown adipocyte differentiation by modulating the phosphorylation of p38 mitogen-activated protein kinase.

    Directory of Open Access Journals (Sweden)

    Hye-Ryung Choi

    Full Text Available Brown adipocytes play an important role in regulating the balance of energy, and as such, there is a strong correlation between obesity and the amount of brown adipose tissue. Although the molecular mechanism underlying white adipocyte differentiation has been well characterized, brown adipocyte differentiation has not been studied extensively. Here, we investigate the potential role of dual-specificity phosphatase 10 (DUSP10 in brown adipocyte differentiation using primary brown preadipocytes.The expression of DUSP10 increased continuously after the brown adipocyte differentiation of mouse primary brown preadipocytes, whereas the phosphorylation of p38 was significantly upregulated at an early stage of differentiation followed by steep downregulation. The overexpression of DUSP10 induced a decrease in the level of p38 phosphorylation, resulting in lower lipid accumulation than that in cells overexpressing the inactive mutant DUSP10. The expression levels of several brown adipocyte markers such as PGC-1α, UCP1, and PRDM16 were also significantly reduced upon the ectopic expression of DUSP10. Furthermore, decreased mitochondrial DNA content was detected in cells expressing DUSP10. The results obtained upon treatment with the p38 inhibitor, SB203580, clearly indicated that the phosphorylation of p38 at an early stage is important in brown adipocyte differentiation. The effect of the p38 inhibitor was partially recovered by DUSP10 knockdown using RNAi.These results suggest that p38 phosphorylation is controlled by DUSP10 expression. Furthermore, p38 phosphorylation at an early stage is critical in brown adipocyte differentiation. Thus, the regulation of DUSP10 activity affects the efficiency of brown adipogenesis. Consequently, DUSP10 can be used as a novel target protein for the regulation of obesity.

  7. 14-3-3{sigma} controls corneal epithelial cell proliferation and differentiation through the Notch signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Xin, Ying [Stem Cell Institute, James Brown Cancer Center, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202 (United States); Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202 (United States); Lu, Qingxian [Tumor Immunobiology Group, James Brown Cancer Center, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202 (United States); Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202 (United States); Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202 (United States); Li, Qiutang, E-mail: q.li@louisville.edu [Stem Cell Institute, James Brown Cancer Center, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202 (United States); Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202 (United States)

    2010-02-19

    14-3-3{sigma} (also called stratifin) is specifically expressed in the stratified squamous epithelium and its function was recently shown to be linked to epidermal stratification and differentiation in the skin. In this study, we investigated its role in corneal epithelium cell proliferation and differentiation. We showed that the 14-3-3{sigma} mutation in repeated epilation (Er) mutant mice results in a dominant negative truncated protein. Primary corneal epithelial cells expressing the dominant negative protein failed to undergo high calcium-induced cell cycle arrest and differentiation. We further demonstrated that blocking endogenous 14-3-3{sigma} activity in corneal epithelial cells by overexpressing dominative negative 14-3-3{sigma} led to reduced Notch activity and Notch1/2 transcription. Significantly, expression of the active Notch intracellular domain overcame the block in epithelial cell differentiation in 14-3-3{sigma} mutant-expressing corneal epithelial cells. We conclude that 14-3-3{sigma} is critical for regulating corneal epithelial proliferation and differentiation by regulating Notch signaling activity.

  8. 14-3-3σ controls corneal epithelial cell proliferation and differentiation through the Notch signaling pathway

    International Nuclear Information System (INIS)

    Xin, Ying; Lu, Qingxian; Li, Qiutang

    2010-01-01

    14-3-3σ (also called stratifin) is specifically expressed in the stratified squamous epithelium and its function was recently shown to be linked to epidermal stratification and differentiation in the skin. In this study, we investigated its role in corneal epithelium cell proliferation and differentiation. We showed that the 14-3-3σ mutation in repeated epilation (Er) mutant mice results in a dominant negative truncated protein. Primary corneal epithelial cells expressing the dominant negative protein failed to undergo high calcium-induced cell cycle arrest and differentiation. We further demonstrated that blocking endogenous 14-3-3σ activity in corneal epithelial cells by overexpressing dominative negative 14-3-3σ led to reduced Notch activity and Notch1/2 transcription. Significantly, expression of the active Notch intracellular domain overcame the block in epithelial cell differentiation in 14-3-3σ mutant-expressing corneal epithelial cells. We conclude that 14-3-3σ is critical for regulating corneal epithelial proliferation and differentiation by regulating Notch signaling activity.

  9. RNase L controls terminal adipocyte differentiation, lipids storage and insulin sensitivity via CHOP10 mRNA regulation

    DEFF Research Database (Denmark)

    Fabre, Odile Martine Julie; Salehzada, T; Lambert, K

    2012-01-01

    Adipose tissue structure is altered during obesity, leading to deregulation of whole-body metabolism. Its function depends on its structure, in particular adipocytes number and differentiation stage. To better understand the mechanisms regulating adipogenesis, we have investigated the role...... is associated with CHOP10 mRNA and regulates its stability. CHOP10 expression is conserved in RNase L(-/-)-MEFs, maintaining preadipocyte state while impairing their terminal differentiation. RNase L(-/-)-MEFs have decreased lipids storage capacity, insulin sensitivity and glucose uptake. Expression of ectopic...... RNase L in RNase L(-/-)-MEFs triggers CHOP10 mRNA instability, allowing increased lipids storage, insulin response and glucose uptake. Similarly, downregulation of CHOP10 mRNA with CHOP10 siRNA in RNase L(-/-)-MEFs improves their differentiation in adipocyte. In vivo, aged RNase L(-)/(-) mice present...

  10. Charge effects controlling the current hysteresis and negative differential resistance in periodical nanosize Si/CaF sub 2 structures

    CERN Document Server

    Berashevich, Y A; Kholod, A N; Borisenko, V E

    2002-01-01

    A kinetic model of charge carrier transport in nanosize periodical Si/CaF sub 2 structures via localized states in dielectric is proposed. Computer simulation of the current-voltage characteristics of such structures has shown that the built-in field arises in a dielectric due to polarization of the trapped charge by localized centers. This results in current hysteresis and negative differential resistance region at the current-voltage characteristics when the bias polarity is changed. At temperature below 250 K, the portion of negative differential resistance vanishes

  11. Controlling the optical path length in turbid media using differential path-length spectroscopy: fiber diameter dependence

    NARCIS (Netherlands)

    Kaspers, O. P.; Sterenborg, H. J. C. M.; Amelink, A.

    2008-01-01

    We have characterized the path length for the differential path-length spectroscopy (DPS) fiber optic geometry for a wide range of optical properties and for fiber diameters ranging from 200 mu m to 1000 mu m. Phantom measurements show that the path length is nearly constant for scattering

  12. Pro-oxidant/antioxidant balance controls pancreatic β-cell differentiation through the ERK1/2 pathway.

    Science.gov (United States)

    Hoarau, E; Chandra, V; Rustin, P; Scharfmann, R; Duvillie, B

    2014-10-23

    During embryogenesis, the intrauterine milieu affects cell proliferation, differentiation, and function by modifying gene expression in susceptible cells, such as the pancreatic β-cells. In this limited energy environment, mitochondrial dysfunction can lead to overproduction of reactive oxygen species (ROS) and to a decline in β-cell function. In opposition to this toxicity, ROS are also required for insulin secretion. Here we investigated the role of ROS in β-cell development. Surprisingly, decreasing ROS production in vivo reduced β-cell differentiation. Moreover, in cultures of pancreatic explants, progenitors were highly sensitive to ROS stimulation and responded by generating β-cells. ROS enhanced β-cell differentiation through modulation of ERK1/2 signaling. Gene transfer and pharmacological manipulations, which diminish cellular ROS levels, also interfered with normal β-cell differentiation. This study highlights the role of the redox balance on β-cell development and provides information that will be useful for improving β-cell production from embryonic stem cells, a step in cell therapy for diabetes.

  13. Gender-Differentiated parenting revisited : Meta-analysis reveals very few differences in parental control of boys and girls

    NARCIS (Netherlands)

    Endendijk, Joyce J.; Groeneveld, Marleen G.; Bakermans-Kranenburg, Marian J.; Mesman, Judi

    2016-01-01

    Although various theories describe mechanisms leading to differential parenting of boys and girls, there is no consensus about the extent to which parents do treat their sons and daughters differently. The last meta-analyses on the subject were conducted more than fifteen years ago, and changes in

  14. IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively

    DEFF Research Database (Denmark)

    Sichien, Dorine; Scott, Charlotte L; Martens, Liesbet

    2016-01-01

    Interferon regulatory factor-8 (IRF8) has been proposed to be essential for development of monocytes, plasmacytoid dendritic cells (pDCs) and type 1 conventional dendritic cells (cDC1s) and remains highly expressed in differentiated DCs. Transcription factors that are required to maintain the ide...

  15. A trained demonstrator has a calming effect on naïve horses when crossing a novel surface

    DEFF Research Database (Denmark)

    Rørvang, Maria Vilain; Ahrendt, Line Peerstrup; Christensen, Janne Winther

    2015-01-01

    horse being led five times across a novel surface. Immediately afterwards the observer horses were given the opportunity to cross the novel surface themselves to obtain food on the other side. Controls (n = 11) were allowed to observe the demonstrator eating on the opposite side of the novel surface...

  16. Cost analysis of the Communication and Low Mood (CALM) randomised trial of behavioural therapy for stroke patients with aphasia.

    Science.gov (United States)

    Humphreys, Ioan; Thomas, Shirley; Phillips, Ceri; Lincoln, Nadina

    2015-01-01

    To evaluate the cost effectiveness of a behavioural therapy intervention shown to be clinically effective in comparison with usual care for stroke patients with aphasia. Randomised controlled trial with comparison of costs and calculation of incremental cost effectiveness ratio. Community. Participants identified as having low mood on either the Visual Analog Mood Scale sad item (≥50) or Stroke Aphasic Depression Questionnaire Hospital version 21 (SADQH21) (≥6) were recruited. Participants were randomly allocated to behavioural therapy or usual care using internet-based randomisation generated in advance of the study by a clinical trials unit. Outcomes were assessed at six months after randomisation, blind to group allocation. The costs were assessed from a service use questionnaire. Effectiveness was defined as the change in SADQH21 scores and a cost-effectiveness analysis was performed comparing the behavioural group with the usual care control group. The cost analysis was undertaken from the perspective of the UK NHS and Social Services. The greatest difference was in home help costs where there was a saving of £56.20 in the intervention group compared to an increase of £61.40 in the control group. At six months the SADQH21 score for the intervention group was 17.3 compared to the control group value of 20.4. This resulted in a mean increase of 0.7 in the control group, compared to a mean significant different decrease of 6 in the intervention group (P = 0.003). The Incremental Cost-Effectiveness Ratio indicated that the cost per point reduction on the SADQH21 was £263. Overall the behavioural therapy was found to improve mood and resulted in some encouraging savings in resource utilisation over the six months follow-up. © The Author(s) 2014.

  17. Prefrontal activation during inhibitory control measured by near-infrared spectroscopy for differentiating between autism spectrum disorders and attention deficit hyperactivity disorder in adults

    Directory of Open Access Journals (Sweden)

    Ayaka Ishii-Takahashi

    2014-01-01

    Full Text Available The differential diagnosis of autism spectrum disorders (ASDs and attention deficit hyperactivity disorder (ADHD based solely on symptomatic and behavioral assessments can be difficult, even for experts. Thus, the development of a neuroimaging marker that differentiates ASDs from ADHD would be an important contribution to this field. We assessed the differences in prefrontal activation between adults with ASDs and ADHD using an entirely non-invasive and portable neuroimaging tool, near-infrared spectroscopy. This study included 21 drug-naïve adults with ASDs, 19 drug-naïve adults with ADHD, and 21 healthy subjects matched for age, sex, and IQ. Oxygenated hemoglobin concentration changes in the prefrontal cortex were assessed during a stop signal task and a verbal fluency task. During the stop signal task, compared to the control group, the ASDs group exhibited lower activation in a broad prefrontal area, whereas the ADHD group showed underactivation of the right premotor area, right presupplementary motor area, and bilateral dorsolateral prefrontal cortices. Significant differences were observed in the left ventrolateral prefrontal cortex between the ASDs and ADHD groups during the stop signal task. The leave-one-out cross-validation method using mean oxygenated hemoglobin changes yielded a classification accuracy of 81.4% during inhibitory control. These results were task specific, as the brain activation pattern observed during the verbal fluency task did not differentiate the ASDs and ADHD groups significantly. This study therefore provides evidence of a difference in left ventrolateral prefrontal activation during inhibitory control between adults with ASDs and ADHD. Thus, near-infrared spectroscopy may be useful as an auxiliary tool for the differential diagnosis of such developmental disorders.

  18. The transcription factor Jdp2 controls bone homeostasis and antibacterial immunity by regulating osteoclast and neutrophil differentiation.

    Science.gov (United States)

    Maruyama, Kenta; Fukasaka, Masahiro; Vandenbon, Alexis; Saitoh, Tatsuya; Kawasaki, Takumi; Kondo, Takeshi; Yokoyama, Kazunari K; Kidoya, Hiroyasu; Takakura, Nobuyuki; Standley, Daron; Takeuchi, Osamu; Akira, Shizuo

    2012-12-14

    Jdp2 is an AP-1 family transcription factor that regulates the epigenetic status of histones. Previous in vitro studies revealed that Jdp2 is involved in osteoclastogenesis. However, the roles of Jdp2 in vivo and its pleiotropic functions are largely unknown. Here we generated Jdp2(-/-) mice and discovered its crucial roles not only in bone metabolism but also in differentiation of neutrophils. Jdp2(-/-) mice exhibited osteopetrosis resulting from impaired osteoclastogenesis. Jdp2(-/-) neutrophils were morphologically normal but had impaired surface expression of Ly6G, bactericidal function, and apoptosis. We also found that ATF3 was an inhibitor of neutrophil differentiation and that Jdp2 directly suppresses its expression via inhibition of histone acetylation. Strikingly, Jdp2(-/-) mice were highly susceptible to Staphylococcus aureus and Candida albicans infection. Thus, Jdp2 plays pivotal roles in in vivo bone homeostasis and host defense by regulating osteoclast and neutrophil differentiation. Copyright © 2012 Elsevier Inc. All rights reserved.

  19. Control of ductal vs. alveolar differentiation of mammary clonogens and susceptibility to radiation-induced mammary cancer

    International Nuclear Information System (INIS)

    Kamiya, Kenji; Yokoro, Kenjiro; Clifton, K.H.; Gould, M.N.

    1991-01-01

    We have developed an in vitro-in vivo transplantation assay for measuring the concentration of clonogenic epithelial cells in cell suspensions of rat mammary tissue. Rat mammary clonogens from organoid cultures are capable of the same degree of PLDR as clonogens in vivo. The growth and differentiation of mammary clonogens to alveolar colonies or ductal colonies is regulated as follows: a) in the presence of E 2 and high prolactin (Prl), cortisol induces mammary clonogens to proliferate and differentiate to form alveolar colonies which secrete milk and begin losing clonogenic potential, b) in cortisol deficient rats, Prl and E 2 synergistically stimulate non-secretory ductal colonies, formation of which retain clonogenic potential, c) E 2 without progesterone stimulates alveolar colony formation in the presence of cortical and high Prl, d) progesterone inhibits mammary clonogen differentiation to milk-producing cells and induces ductogenesis in a dose responsive fashion in the presence of E 2 , cortisol and high Prl. High prolactin levels coupled with glucocorticoid deficiency increases the susceptibility to mammary carcinogenesis following low dose radiation exposure by increasing the number of total mammary clonogens which are the presumptive target cells and by stimulating their proliferation after exposure. (author)

  20. Engineered Biomaterials Control Differentiation and Proliferation of Human-Embryonic-Stem-Cell-Derived Cardiomyocytes via Timed Notch Activation

    Directory of Open Access Journals (Sweden)

    Jason C. Tung

    2014-03-01

    Full Text Available For cell-based treatments of myocardial infarction, a better understanding of key developmental signaling pathways and more robust techniques for producing cardiomyocytes are required. Manipulation of Notch signaling has promise as it plays an important role during cardiovascular development, but previous studies presented conflicting results that Notch activation both positively and negatively regulates cardiogenesis. We developed surface- and microparticle-based Notch-signaling biomaterials that function in a time-specific activation-tunable manner, enabling precise investigation of Notch activation at specific developmental stages. Using our technologies, a biphasic effect of Notch activation on cardiac differentiation was found: early activation in undifferentiated human embryonic stem cells (hESCs promotes ectodermal differentiation, activation in specified cardiovascular progenitor cells increases cardiac differentiation. Signaling also induces cardiomyocyte proliferation, and repeated doses of Notch-signaling microparticles further enhance cardiomyocyte population size. These results highlight the diverse effects of Notch activation during cardiac development and provide approaches for generating large quantities of cardiomyocytes.

  1. Quasi-minimal active disturbance rejection control of MIMO perturbed linear systems based on differential neural networks and the attractive ellipsoid method.

    Science.gov (United States)

    Salgado, Iván; Mera-Hernández, Manuel; Chairez, Isaac

    2017-11-01

    This study addresses the problem of designing an output-based controller to stabilize multi-input multi-output (MIMO) systems in the presence of parametric disturbances as well as uncertainties in the state model and output noise measurements. The controller design includes a linear state transformation which separates uncertainties matched to the control input and the unmatched ones. A differential neural network (DNN) observer produces a nonlinear approximation of the matched perturbation and the unknown states simultaneously in the transformed coordinates. This study proposes the use of the Attractive Ellipsoid Method (AEM) to optimize the gains of the controller and the gain observer in the DNN structure. As a consequence, the obtained control input minimizes the convergence zone for the estimation error. Moreover, the control design uses the estimated disturbance provided by the DNN to obtain a better performance in the stabilization task in comparison with a quasi-minimal output feedback controller based on a Luenberger observer and a sliding mode controller. Numerical results pointed out the advantages obtained by the nonlinear control based on the DNN observer. The first example deals with the stabilization of an academic linear MIMO perturbed system and the second example stabilizes the trajectories of a DC-motor into a predefined operation point. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

  2. Differential gene expression in liver and small intestine from lactating rats compared to age-matched virgin controls detects increased mRNA of cholesterol biosynthetic genes

    Directory of Open Access Journals (Sweden)

    Jungsuwadee Paiboon

    2011-02-01

    Full Text Available Abstract Background Lactation increases energy demands four- to five-fold, leading to a two- to three-fold increase in food consumption, requiring a proportional adjustment in the ability of the lactating dam to absorb nutrients and to synthesize critical biomolecules, such as cholesterol, to meet the dietary needs of both the offspring and the dam. The size and hydrophobicity of the bile acid pool increases during lactation, implying an increased absorption and disposition of lipids, sterols, nutrients, and xenobiotics. In order to investigate changes at the transcriptomics level, we utilized an exon array and calculated expression levels to investigate changes in gene expression in the liver, duodenum, jejunum, and ileum of lactating dams when compared against age-matched virgin controls. Results A two-way mixed models ANOVA was applied to detect differentially expressed genes. Significance calls were defined as a p Cyp7a1, which catalyzes the rate limiting step in the bile acid biosynthetic pathway, was also significantly increased in liver. In addition, decreased levels of mRNA associated with T-cell signaling were found in the jejunum and ileum. Several members of the Solute Carrier (SLC and Adenosine Triphosphate Binding Cassette (ABC superfamilies of membrane transporters were found to be differentially expressed; these genes may play a role in differences in nutrient and xenobiotic absorption and disposition. mRNA expression of SLC39a4_predicted, a zinc transporter, was increased in all tissues, suggesting that it is involved in increased zinc uptake during lactation. Microarray data are available through GEO under GSE19175. Conclusions We detected differential expression of mRNA from several pathways in lactating dams, including upregulation of the cholesterol biosynthetic pathway in liver and intestine, consistent with Srebp activation. Differential T-Cell signaling in the two most distal regions of the small intestine (ileum and

  3. Good Child is a Calm Child: Mothers' Social Status, Maternal Conceptions of Proper Demeanor, and Stranger Anxiety in One-Year Old Cameroonian Nso Children

    Directory of Open Access Journals (Sweden)

    Hiltrud Otto

    2015-04-01

    Full Text Available Our article questions the assumption that stranger anxiety develops universally in children; thereby our study is rooted in a long tradition in psychological anthropology of testing the universality of theories formulated in Western society. We argue that the infant's behavior towards strangers is the product of socialization processes that represent adaptations to cultural contexts. Our study investigates the ethnotheory of childrearing and the development of stranger anxiety in a Cameroonian community of traditional Nso farmers. The participants of the study were 29 Cameroonian Nso mothers with one-year old children. Using a multi-method approach, we demonstrate that Nso mothers value inexpressive infants that adjust easily to others. Accordingly, a considerably large number of one-year old Nso infants showed no stranger anxiety when encountered by a stranger. Maternal social status and her social support system proved crucial to successful implementation of the socialization goal of a calm child. Our data support the view that child behavior is a product of culturally constructed experiences of daily life. The acknowledgement of the cultural construction of stranger anxiety carries implications for developmental theories, especially for attachment theory, which relies on the universality of stranger anxiety in their most acclaimed paradigm, the Strange Situation.

  4. Bistability and hysteresis of the 'Secteur' differentiation are controlled by a two-gene locus in Nectria haematococca

    Directory of Open Access Journals (Sweden)

    Daboussi Marie-Josée

    2004-08-01

    Full Text Available Abstract Background Bistability and hysteresis are increasingly recognized as major properties of regulatory networks governing numerous biological phenomena, such as differentiation and cell cycle progression. The full scope of the underlying molecular mechanisms leading to bistability and hysteresis remains elusive. Nectria haemaotcocca, a saprophytic or pathogenic fungus with sexual reproduction, exhibits a bistable morphological modification characterized by a reduced growth rate and an intense pigmentation. Bistability is triggered by the presence or absence of σ, a cytoplasmic determinant. This determinant spreads in an infectious manner in the hyphae of the growing margin, insuring hysteresis of the differentiation. Results Seven mutants specifically affected in the generation of σ were selected through two different screening strategies. The s1 and s2 mutations completely abolish the generation of σ and of its morphological expression, the Secteur. The remaining five mutations promote its constitutive generation, which determines an intense pigmentation but not growth alteration. The seven mutations map at the same locus, Ses (for 'Secteur-specific'. The s2 mutant was obtained by an insertional mutagenesis strategy, which permitted the cloning of the Ses locus. Sequence and transcription analysis reveals that Ses is composed of two closely linked genes, SesA, mutated in the s1 and s2 mutant strains, and SesB, mutated in the s* mutant strains. SesB shares sequence similarity with animal and fungal putative proteins, with potential esterase/lipase/thioesterase activity, whereas SesA is similar to proteins of unknown function present only in the filamentous fungi Fusarium graminearum and Podospora anserina. Conclusions The cloning of Ses provides evidence that a system encoded by two linked genes directs a bistable and hysteretic switch in a eukaryote. Atypical regulatory relations between the two proteins may account for the hysteresis

  5. Bistability and hysteresis of the 'Secteur' differentiation are controlled by a two-gene locus in Nectria haematococca

    Science.gov (United States)

    Graziani, Stéphane; Silar, Philippe; Daboussi, Marie-Josée

    2004-01-01

    Background Bistability and hysteresis are increasingly recognized as major properties of regulatory networks governing numerous biological phenomena, such as differentiation and cell cycle progression. The full scope of the underlying molecular mechanisms leading to bistability and hysteresis remains elusive. Nectria haemaotcocca, a saprophytic or pathogenic fungus with sexual reproduction, exhibits a bistable morphological modification characterized by a reduced growth rate and an intense pigmentation. Bistability is triggered by the presence or absence of σ, a cytoplasmic determinant. This determinant spreads in an infectious manner in the hyphae of the growing margin, insuring hysteresis of the differentiation. Results Seven mutants specifically affected in the generation of σ were selected through two different screening strategies. The s1 and s2 mutations completely abolish the generation of σ and of its morphological expression, the Secteur. The remaining five mutations promote its constitutive generation, which determines an intense pigmentation but not growth alteration. The seven mutations map at the same locus, Ses (for 'Secteur-specific'). The s2 mutant was obtained by an insertional mutagenesis strategy, which permitted the cloning of the Ses locus. Sequence and transcription analysis reveals that Ses is composed of two closely linked genes, SesA, mutated in the s1 and s2 mutant strains, and SesB, mutated in the s* mutant strains. SesB shares sequence similarity with animal and fungal putative proteins, with potential esterase/lipase/thioesterase activity, whereas SesA is similar to proteins of unknown function present only in the filamentous fungi Fusarium graminearum and Podospora anserina. Conclusions The cloning of Ses provides evidence that a system encoded by two linked genes directs a bistable and hysteretic switch in a eukaryote. Atypical regulatory relations between the two proteins may account for the hysteresis of Secteur differentiation

  6. On Optimality Conditions in Control of Elliptic Variational Inequalities

    Czech Academy of Sciences Publication Activity Database

    Outrata, Jiří; Jarušek, Jiří; Stará, J.

    2011-01-01

    Roč. 19, č. 1 (2011), s. 23-42 ISSN 1877-0533 R&D Projects: GA AV ČR IAA100750802; GA ČR GA201/09/0917 Institutional research plan: CEZ:AV0Z10750506; CEZ:AV0Z10190503 Keywords : Directional differentiability * Critical cone * Strong local fuzzy sum rule * Calmness * Capacity Subject RIV: BA - General Mathematics Impact factor: 0.791, year: 2011

  7. Keep calm and carry on: improved frustration tolerance and processing speed by transcranial direct current stimulation (tDCS.

    Directory of Open Access Journals (Sweden)

    Christian Plewnia

    Full Text Available Cognitive control (CC of attention is a major prerequisite for effective information processing. Emotional distractors can bias and impair goal-directed deployment of attentional resources. Frustration-induced negative affect and cognition can act as internal distractors with negative impact on task performance. Consolidation of CC may thus support task-oriented behavior under challenging conditions. Recently, transcranial direct current stimulation (tDCS has been put forward as an effective tool to modulate CC. Particularly, anodal, activity enhancing tDCS to the left dorsolateral prefrontal cortex (dlPFC can increase insufficient CC in depression as indicated by a reduction of attentional biases induced by emotionally salient stimuli. With this study, we provide first evidence that, compared to sham stimulation, tDCS to the left dlPFC enhances processing speed measured by an adaptive version of the Paced Auditory Serial Addition Task (PASAT that is typically thwarted by frustration. Notably, despite an even larger amount of error-related negative feedback, the task-induced upset was suppressed in the group receiving anodal tDCS. Moreover, inhibition of task-related negative affect was correlated with performance gains, suggesting a close link between enhanced processing speed and consolidation of CC by tDCS. Together, these data provide first evidence that activity enhancing anodal tDCS to the left dlPFC can support focused cognitive processing particularly when challenged by frustration-induced negative affect.

  8. Keep calm and carry on: improved frustration tolerance and processing speed by transcranial direct current stimulation (tDCS).

    Science.gov (United States)

    Plewnia, Christian; Schroeder, Philipp A; Kunze, Roland; Faehling, Florian; Wolkenstein, Larissa

    2015-01-01

    Cognitive control (CC) of attention is a major prerequisite for effective information processing. Emotional distractors can bias and impair goal-directed deployment of attentional resources. Frustration-induced negative affect and cognition can act as internal distractors with negative impact on task performance. Consolidation of CC may thus support task-oriented behavior under challenging conditions. Recently, transcranial direct current stimulation (tDCS) has been put forward as an effective tool to modulate CC. Particularly, anodal, activity enhancing tDCS to the left dorsolateral prefrontal cortex (dlPFC) can increase insufficient CC in depression as indicated by a reduction of attentional biases induced by emotionally salient stimuli. With this study, we provide first evidence that, compared to sham stimulation, tDCS to the left dlPFC enhances processing speed measured by an adaptive version of the Paced Auditory Serial Addition Task (PASAT) that is typically thwarted by frustration. Notably, despite an even larger amount of error-related negative feedback, the task-induced upset was suppressed in the group receiving anodal tDCS. Moreover, inhibition of task-related negative affect was correlated with performance gains, suggesting a close link between enhanced processing speed and consolidation of CC by tDCS. Together, these data provide first evidence that activity enhancing anodal tDCS to the left dlPFC can support focused cognitive processing particularly when challenged by frustration-induced negative affect.

  9. The nuclear hormone receptor family member NR5A2 controls aspects of multipotent progenitor cell formation and acinar differentiation during pancreatic organogenesis.

    Science.gov (United States)

    Hale, Michael A; Swift, Galvin H; Hoang, Chinh Q; Deering, Tye G; Masui, Toshi; Lee, Youn-Kyoung; Xue, Jumin; MacDonald, Raymond J

    2014-08-01

    The orphan nuclear receptor NR5A2 is necessary for the stem-like properties of the epiblast of the pre-gastrulation embryo and for cellular and physiological homeostasis of endoderm-derived organs postnatally. Using conditional gene inactivation, we show that Nr5a2 also plays crucial regulatory roles during organogenesis. During the formation of the pancreas, Nr5a2 is necessary for the expansion of the nascent pancreatic epithelium, for the subsequent formation of the multipotent progenitor cell (MPC) population that gives rise to pre-acinar cells and bipotent cells with ductal and islet endocrine potential, and for the formation and differentiation of acinar cells. At birth, the NR5A2-deficient pancreas has defects in all three epithelial tissues: a partial loss of endocrine cells, a disrupted ductal tree and a >90% deficit of acini. The acinar defects are due to a combination of fewer MPCs, deficient allocation of those MPCs to pre-acinar fate, disruption of acinar morphogenesis and incomplete acinar cell differentiation. NR5A2 controls these developmental processes directly as well as through regulatory interactions with other pancreatic transcriptional regulators, including PTF1A, MYC, GATA4, FOXA2, RBPJL and MIST1 (BHLHA15). In particular, Nr5a2 and Ptf1a establish mutually reinforcing regulatory interactions and collaborate to control developmentally regulated pancreatic genes by binding to shared transcriptional regulatory regions. At the final stage of acinar cell development, the absence of NR5A2 affects the expression of Ptf1a and its acinar specific partner Rbpjl, so that the few acinar cells that form do not complete differentiation. Nr5a2 controls several temporally distinct stages of pancreatic development that involve regulatory mechanisms relevant to pancreatic oncogenesis and the maintenance of the exocrine phenotype. © 2014. Published by The Company of Biologists Ltd.

  10. Targeting CD28, CTLA-4 and PD-L1 costimulation differentially controls immune synapses and function of human regulatory and conventional T-cells.

    Directory of Open Access Journals (Sweden)

    Nahzli Dilek

    Full Text Available CD28, CTLA-4 and PD-L1, the three identified ligands for CD80/86, are pivotal positive and negative costimulatory molecules that, among other functions, control T cell motility and formation of immune synapse between T cells and antigen-presenting cells (APCs. What remains incompletely understood is how CD28 leads to the activation of effector T cells (Teff but inhibition of suppression by regulatory T cells (Tregs, while CTLA-4 and PD-L1 inhibit Teff function but are crucial for the suppressive function of Tregs. Using alloreactive human T cells and blocking antibodies, we show here by live cell dynamic microscopy that CD28, CTLA-4, and PD-L1 differentially control velocity, motility and immune synapse formation in activated Teff versus Tregs. Selectively antagonizing CD28 costimulation increased Treg dwell time with APCs and induced calcium mobilization which translated in increased Treg suppressive activity, in contrast with the dampening effect on Teff responses. The increase in Treg suppressive activity after CD28 blockade was also confirmed with polyclonal Tregs. Whereas CTLA-4 played a critical role in Teff by reversing TCR-induced STOP signals, it failed to affect motility in Tregs but was essential for formation of the Treg immune synapse. Furthermore, we identified a novel role for PD-L1-CD80 interactions in suppressing motility specifically in Tregs. Thus, our findings reveal that the three identified ligands of CD80/86, CD28, CTLA-4 and PD-L1, differentially control immune synapse formation and function of the human Teff and Treg cells analyzed here. Individually targeting CD28, CTLA-4 and PD-L1 might therefore represent a valuable therapeutic strategy to treat immune disorders where effector and regulatory T cell functions need to be differentially targeted.

  11. Study on Differential Regenerative Braking Torque Control to Increase the Stability of the Small Electric Vehicle with Four In-Wheel Motors

    Directory of Open Access Journals (Sweden)

    Ali N. M.

    2017-01-01

    Full Text Available Based on the advantages of the electric motor such as fast and precise torque response, the performance of the electric vehicle (EV can be improved. During braking or driving on the cornering, the vehicle will over steer or under steer if a car turns by more or less than the amount commanded by the driver. To improve the stability of the small EV with four in-wheel motors, the differential regenerative braking torque control is proposed. In this system, the regenerative braking torque at each wheel will be controlled individually based on the value of slip ratio. If the slip ratio is greater than the optimum value, the regenerative brake will turn off. In this situation, the electric motor will not produce the regenerative braking torque. Conversely, if the slip ratio lower than the optimum value, the regenerative brake will turn on and the electric motor will generate the regenerative braking torque. In the numerical analysis, to investigate the effectiveness of the proposed model, the road condition is set to an icy road on the left tire and dry asphalt on the right tire. From the simulation results, the differential regenerative braking torque control can prevent the tire from lock-up and avoid the vehicle from skidding.

  12. MAPK pathway control of stem cell proliferation and differentiation in the embryonic pituitary provides insights into the pathogenesis of papillary craniopharyngioma.

    Science.gov (United States)

    Haston, Scott; Pozzi, Sara; Carreno, Gabriela; Manshaei, Saba; Panousopoulos, Leonidas; Gonzalez-Meljem, Jose Mario; Apps, John R; Virasami, Alex; Thavaraj, Selvam; Gutteridge, Alice; Forshew, Tim; Marais, Richard; Brandner, Sebastian; Jacques, Thomas S; Andoniadou, Cynthia L; Martinez-Barbera, Juan Pedro

    2017-06-15

    Despite the importance of the RAS-RAF-MAPK pathway in normal physiology and disease of numerous organs, its role during pituitary development and tumourigenesis remains largely unknown. Here, we show that the over-activation of the MAPK pathway, through conditional expression of the gain-of-function alleles BrafV600E and KrasG12D in the developing mouse pituitary, results in severe hyperplasia and abnormal morphogenesis of the gland by the end of gestation. Cell-lineage commitment and terminal differentiation are disrupted, leading to a significant reduction in numbers of most of the hormone-producing cells before birth, with the exception of corticotrophs. Of note, Sox2 + stem cells and clonogenic potential are drastically increased in the mutant pituitaries. Finally, we reveal that papillary craniopharyngioma (PCP), a benign human pituitary tumour harbouring BRAF p.V600E also contains Sox2 + cells with sustained proliferative capacity and disrupted pituitary differentiation. Together, our data demonstrate a crucial function of the MAPK pathway in controlling the balance between proliferation and differentiation of Sox2 + cells and suggest that persistent proliferative capacity of Sox2 + cells may underlie the pathogenesis of PCP. © 2017. Published by The Company of Biologists Ltd.

  13. Differential effect of exposure-based therapy and cognitive therapy on post-traumatic stress disorder symptom clusters: A randomized controlled trial.

    Science.gov (United States)

    Horesh, Danny; Qian, Meng; Freedman, Sara; Shalev, Arieh

    2017-06-01

    A question remains regarding differential effects of exposure-based versus non-exposure-based therapies on specific post-traumatic stress disorder (PTSD) symptom clusters. Traumatized emergency room patients were randomized to receive prolonged exposure (PE) or cognitive therapy (CT) without exposure. PE/CT had no differential effect on individual symptom clusters, and change in total PTSD score remained significant even after controlling for the reductions in all three symptom clusters. In addition, baseline levels of PTSD avoidance/intrusion/hyperarousal did not moderate the effects of PE and CT on total PTSD symptom scores. Taken together, these findings challenge the notion that PE and CT are specifically, and differentially, useful in treating one particular PTSD symptom cluster. Despite their different theoretical backgrounds and techniques, the notion that PE and CT (without exposure) target different PTSD symptoms was not confirmed in this study. Thus, both interventions may in fact be equally effective for treating intrusion, avoidance and hyperarousal symptoms. Baseline levels of avoidance, intrusion and hyperarousal may not be good a priori indicators for PTSD treatment selection. The effect of PE and CT on PTSD as a whole does not seem to depend on a reduction in any specific symptom cluster. These findings indicate that exposure and non-exposure interventions may lead to similar results in terms of reductions in specific PTSD symptoms. It is quite possible that individual PTSD clusters may respond to therapy in an inter-related fashion, with one cluster affecting the other. © 2016 The British Psychological Society.

  14. The zinc sensing receptor, ZnR/GPR39, controls proliferation and differentiation of colonocytes and thereby tight junction formation in the colon.

    Science.gov (United States)

    Cohen, L; Sekler, I; Hershfinkel, M

    2014-06-26

    The intestinal epithelium is a renewable tissue that requires precise balance between proliferation and differentiation, an essential process for the formation of a tightly sealed barrier. Zinc deficiency impairs the integrity of the intestinal epithelial barrier and is associated with ulcerative and diarrheal pathologies, but the mechanisms underlying the role of Zn(2+) are not well understood. Here, we determined a role of the colonocytic Zn(2+) sensing receptor, ZnR/GPR39, in mediating Zn(2+)-dependent signaling and regulating the proliferation and differentiation of colonocytes. Silencing of ZnR/GPR39 expression attenuated Zn(2+)-dependent activation of ERK1/2 and AKT as well as downstream activation of mTOR/p70S6K, pathways that are linked with proliferation. Consistently, ZnR/GPR39 silencing inhibited HT29 and Caco-2 colonocyte proliferation, while not inducing caspase-3 cleavage. Remarkably, in differentiating HT29 colonocytes, silencing of ZnR/GPR39 expression inhibited alkaline phosphatase activity, a marker of differentiation. Furthermore, Caco-2 colonocytes showed elevated expression of ZnR/GPR39 during differentiation, whereas silencing of ZnR/GPR39 decreased monolayer transepithelial electrical resistance, suggesting compromised barrier formation. Indeed, silencing of ZnR/GPR39 or chelation of Zn(2+) by the cell impermeable chelator CaEDTA was followed by impaired expression of the junctional proteins, that is, occludin, zonula-1 (ZO-1) and E-cadherin. Importantly, colon tissues of GPR39 knockout mice also showed a decrease in expression levels of ZO-1 and occludin compared with wildtype mice. Altogether, our results indicate that ZnR/GPR39 has a dual role in promoting proliferation of colonocytes and in controlling their differentiation. The latter is followed by ZnR/GPR39-dependent expression of tight junctional proteins, thereby leading to formation of a sealed intestinal epithelial barrier. Thus, ZnR/GPR39 may be a therapeutic target for promoting

  15. Controlling Personal Rewards: Professional Teachers' Differential Use of Feedback and the Effects of Feedback on the Student's Motivation to Perform

    Science.gov (United States)

    Cooper, Harris M.

    1977-01-01

    The hypothesis that teachers criticize low-expectation students in order to control reinforcement schedules was tested. Teacher expectation, teacher perception of control, criticism of students, academic behavior, and student perception of teacher response to student effort were examined in six primary grade classes. Implications concerning…

  16. Motor-evoked potential amplitudes elicited by transcranial magnetic stimulation do not differentiate between patients and normal controls.

    Science.gov (United States)

    Grunhaus, Leon; Polak, Dana; Amiaz, Revital; Dannon, Pinhas N

    2003-12-01

    Transcranial magnetic stimulation (TMS) applied over the motor cortex depolarizes neurons and leads to motor-evoked potentials (MEP). To assess cortico-spinal excitability we compared the motor threshold (MT) and the averaged MEP amplitude generated by TMS in patients with major depression (MD) and matched controls. Nineteen patients, who where participants in a protocol comparing the antidepressant effects of rTMS with those of ECT, and thirteen age- and gender-matched normal controls were studied. MT was similar between patients and normal controls. The MEP amplitude response was significantly increased by rTMS, however, the magnitude of the response was similar in patients and normal controls. Correlations between the averaged MEP amplitude and age revealed that older subjects demonstrated significantly lower responses at all time-points. We conclude that cortico-spinal excitability is increased following rTMS, however, differences between patients and normal controls were not apparent with the paradigm used.

  17. Differentiation of African components of ancestry to stratify groups in a case-control study of a Brazilian urban population.

    Science.gov (United States)

    Silbiger, Vivian N; Hirata, Mario H; Luchessi, Andre D; Genvigir, Fabiana D V; Cerda, Alvaro; Rodrigues, Alice C; Willrich, Maria A V; Arazi, Simone S; Dorea, Egidio L; Bernik, Marcia M S; Faludi, Andre A; Bertolami, Marcelo C; Santos, Carla; Carracedo, Angel; Salas, Antonio; Freire, Ana; Lareu, Maria Victoria; Phillips, Christopher; Porras-Hurtado, Liliana; Fondevila, Manuel; Hirata, Rosario D C

    2012-06-01

    Balancing the subject composition of case and control groups to create homogenous ancestries between each group is essential for medical association studies. We explored the applicability of single-tube 34-plex ancestry informative markers (AIM) single nucleotide polymorphisms (SNPs) to estimate the African Component of Ancestry (ACA) to design a future case-control association study of a Brazilian urban sample. One hundred eighty individuals (107 case group; 73 control group) self-described as white, brown-intermediate or black were selected. The proportions of the relative contribution of a variable number of ancestral population components were similar between case and control groups. Moreover, the case and control groups demonstrated similar distributions for ACA 0.50 categories. Notably a high number of outlier values (23 samples) were observed among individuals with ACA population. This can be achieved using a straight forward multiplexed AIM-SNPs assay of highly discriminatory ancestry markers.

  18. Influence of the circuit impedance on an electron beam controlled diffuse discharge with a negative differential conductivity

    International Nuclear Information System (INIS)

    Schaefer, G.; Schoenbach, K.H.; Kristiansen, M.; Strickland, B.E.; Korzekwa, R.A.; Hutcheson, G.Z.

    1986-01-01

    The use of attaching gases in an externally sustained diffuse discharge opening switch with a low attachment rate at low values of E/N and a high attachment rate at high values of E/N allows the discharge to operate with low losses in the closed switch phase and to achieve fast opening after the sustainment source is turned off. Such an attacher generates a J-E/N characteristic with a negative differential conductivity in an intermediate E/N range. Such a characteristic obstructs the closing process of the discharge if it is operated in a high impedance system. Experiments demonstrating these effects are presented for electron beam sustained discharges in mixtures of argon and C 2 F 6

  19. Intelligence, creativity, and cognitive control: The common and differential involvement of executive functions in intelligence and creativity

    Science.gov (United States)

    Benedek, Mathias; Jauk, Emanuel; Sommer, Markus; Arendasy, Martin; Neubauer, Aljoscha C.

    2014-01-01

    Intelligence and creativity are known to be correlated constructs suggesting that they share a common cognitive basis. The present study assessed three specific executive abilities – updating, shifting, and inhibition – and examined their common and differential relations to fluid intelligence and creativity (i.e., divergent thinking ability) within a latent variable model approach. Additionally, it was tested whether the correlation of fluid intelligence and creativity can be explained by a common executive involvement. As expected, fluid intelligence was strongly predicted by updating, but not by shifting or inhibition. Creativity was predicted by updating and inhibition, but not by shifting. Moreover, updating (and the personality factor openness) was found to explain a relevant part of the shared variance between intelligence and creativity. The findings provide direct support for the executive involvement in creative thought and shed further light on the functional relationship between intelligence and creativity. PMID:25278640

  20. Personality and Differential Treatment Response in Major Depression: A Randomized Controlled Trial Comparing Cognitive-Behavioural Therapy and Pharmacotherapy

    Science.gov (United States)

    Bagby, R Michael; Quilty, Lena C; Segal, Zindel V; McBride, Carolina C; Kennedy, Sidney H; Costa, Paul T

    2008-01-01

    Objective Effective treatments for major depressive disorder exist, yet some patients fail to respond, or achieve only partial response. One approach to optimizing treatment success is to identify which patients are more likely to respond best to which treatments. The objective of this investigation was to determine if patient personality characteristics are predictive of response to either cognitive-behavioural therapy (CBT) or pharmacotherapy (PHT). Method Depressed patients completed the Revised NEO Personality Inventory, which measures the higher-order domain and lower-order facet traits of the Five-Factor Model of Personality, and were randomized to receive either CBT or PHT. Result Four personality traits—the higher-order domain neuroticism and 3 lower-order facet traits: trust, straightforwardness, and tendermindedness—were able to distinguish a differential response rate to CBT, compared with PHT. Conclusion The assessment of patient dimensional personality traits can assist in the selection and optimization of treatment response for depressed patients. PMID:18616856

  1. Controllable Negative Differential Resistance Behavior of an Azobenzene Molecular Device Induced by Different Molecule-Electrode Distances

    International Nuclear Information System (INIS)

    Fan Zhi-Qiang; Zhang Zhen-Hua; Qiu Ming; Deng Xiao-Qing; Tang Gui-Ping

    2012-01-01

    We report the ab initio calculations of transport behaviors of an azobenzene molecular device which is similar to the experimental configurations. The calculated results show that the transport behaviors of the device are sensitive to the molecule-electrode distance and the currents will drop rapidly when the molecule-electrode distance changes from 1.7 Å to 2.0 Å. More interestingly, the negative differential resistance behavior can be found in our device. Nevertheless, it is not the inherent property of an azobenzene molecular device but an effect of the molecule-electrode distance. Detailed analyses of the molecular projected self-consistent Hamiltonian states and the transmission spectra of the system reveal the physical mechanism of these behaviors. (condensed matter: electronic structure, electrical, magnetic, and optical properties)

  2. Characterization of phase change materials for thermal control of photovoltaics using Differential Scanning Calorimetry and Temperature History Method

    International Nuclear Information System (INIS)

    Hasan, A.; McCormack, S.J.; Huang, M.J.; Norton, B.

    2014-01-01

    Highlights: • Five PCM are characterized using tow techniques for PV temperature regulation. • Thermophysical properties of interest are determined and compared with literature. • Determined PCM properties are discussed as criteria for PV temperature regulation. • One PCM identified as potential candidate for PV temperature regulation. - Abstract: Five solid–liquid phase change materials comprising three basic classes, paraffin waxes, salt hydrates and mixtures of fatty acids were thermophysically characterized for thermal regulation applications in photovoltaics. The PCM were investigated using Differential Scanning Calorimetry and Temperature History Method to find their thermophysical properties of interest. The relationship between thermophysical properties of the PCM and their choice as temperature regulators in photovoltaics is discussed in relation to the ambient conditions under which PV systems operate

  3. Uhrf1 Controls iNKT Cell Survival and Differentiation through the Akt-mTOR Axis

    Directory of Open Access Journals (Sweden)

    Yu Cui

    2016-04-01

    Full Text Available Uhrf1 (also known as Np95 is a regulator of DNA methylation and histone ubiquitination and plays an important role in embryogenesis and tumorigenesis. Here, we report that Uhrf1 is essential for invariant natural killer T (iNKT cell development. We found that Uhrf1 was significantly upregulated in stage 1 iNKT cells. Targeted disruption of Uhrf1 resulted in stage 1-specific transition defects as observed by not only increased apoptosis, but also aberrant effector differentiation, which eventually led to the impaired generation of iNKT cells in Uhrf1-deficient mice. Notably, Uhrf1 deficiency resulted in attenuated activation of Akt-mTOR signaling in stage 1 iNKT cells and overexpression of active Akt rescued iNKT cell developmental defects. Collectively, our results suggest that Uhrf1 regulation of the Akt-mTOR signaling pathway is required for iNKT cell development.

  4. Control of Anther Cell Differentiation by the Small Protein Ligand TPD1 and Its Receptor EMS1 in Arabidopsis.

    Directory of Open Access Journals (Sweden)

    Jian Huang

    2016-08-01

    Full Text Available A fundamental feature of sexual reproduction in plants and animals is the specification of reproductive cells that conduct meiosis to form gametes, and the associated somatic cells that provide nutrition and developmental cues to ensure successful gamete production. The anther, which is the male reproductive organ in seed plants, produces reproductive microsporocytes (pollen mother cells and surrounding somatic cells. The microsporocytes yield pollen via meiosis, and the somatic cells, particularly the tapetum, are required for the normal development of pollen. It is not known how the reproductive cells affect the differentiation of these somatic cells, and vice versa. Here, we use molecular genetics, cell biological, and biochemical approaches to demonstrate that TPD1 (TAPETUM DETERMINANT1 is a small secreted cysteine-rich protein ligand that interacts with the LRR (Leucine-Rich Repeat domain of the EMS1 (EXCESS MICROSPOROCYTES1 receptor kinase at two sites. Analyses of the expressions and localizations of TPD1 and EMS1, ectopic expression of TPD1, experimental missorting of TPD1, and ablation of microsporocytes yielded results suggesting that the precursors of microsporocyte/microsporocyte-derived TPD1 and pre-tapetal-cell-localized EMS1 initially promote the periclinal division of secondary parietal cells and then determine one of the two daughter cells as a functional tapetal cell. Our results also indicate that tapetal cells suppress microsporocyte proliferation. Collectively, our findings show that tapetal cell differentiation requires reproductive-cell-secreted TPD1, illuminating a novel mechanism whereby signals from reproductive cells determine somatic cell fate in plant sexual reproduction.

  5. Identification of differentially expressed genes induced by energy restriction using annealing control primer system from the liver and adipose tissues of broilers.

    Science.gov (United States)

    Wang, J W; Chen, W; Kang, X T; Huang, Y Q; Tian, Y D; Wang, Y B

    2012-04-01

    Female Arbor Acre broilers were divided into 2 groups at 18 d of age. One group of chickens had free access to feed (AL), and the other group of chickens had 30% energy restriction (ER). Adipose and hepatic RNA samples were collected at 48 d of age. We employed an accurate reverse-transcription (RT) PCR method that involves annealing control primers to identify the differentially expressed genes (DEG) between ER and AL groups. Using 20 annealing control primers, 43 differentially expressed bands (40 downregulated and 3 upregulated in the ER group) were detected from the hepatic tissue, whereas no differentially expressed bands were detected from the adipose tissue. It seems that energy restriction could induce more DEG in hepatic tissue than that in adipose tissue and could result in more gene-expression downregulation in hepatic tissue. Eight DEG (6 known and 2 unknown genes) were gained from hepatic tissue and confirmed by RT-PCR, which were all supported by released expressed sequence tag sequences. Their expressions were all downregulated by energy restriction in hepatic tissues. Six known genes are RPL7, RPLP1, FBXL12, ND1, ANTXR2, and SLC22A18, respectively, which seem to play essential roles in the protein translation, energy metabolism, and tumor inhibition. The alterations of gene expression in 3 selected genes, including ND1 (P < 0.01), FBXL12 (P < 0.01), and RPLP1 (P < 0.05), were supported by real-time quantitative RT-PCR reaction. Our data provide new insights on the metabolic state of broilers changed by energy restriction.

  6. P2X7 receptor drives Th1 cell differentiation and controls the follicular helper T cell population to protect against Plasmodium chabaudi malaria.

    Directory of Open Access Journals (Sweden)

    Érika Machado de Salles

    2017-08-01

    Full Text Available A complete understanding of the mechanisms underlying the acquisition of protective immunity is crucial to improve vaccine strategies to eradicate malaria. However, it is still unclear whether recognition of damage signals influences the immune response to Plasmodium infection. Adenosine triphosphate (ATP accumulates in infected erythrocytes and is released into the extracellular milieu through ion channels in the erythrocyte membrane or upon erythrocyte rupture. The P2X7 receptor senses extracellular ATP and induces CD4 T cell activation and death. Here we show that P2X7 receptor promotes T helper 1 (Th1 cell differentiation to the detriment of follicular T helper (Tfh cells during blood-stage Plasmodium chabaudi malaria. The P2X7 receptor was activated in CD4 T cells following the rupture of infected erythrocytes and these cells became highly responsive to ATP during acute infection. Moreover, mice lacking the P2X7 receptor had increased susceptibility to infection, which correlated with impaired Th1 cell differentiation. Accordingly, IL-2 and IFNγ secretion, as well as T-bet expression, critically depended on P2X7 signaling in CD4 T cells. Additionally, P2X7 receptor controlled the splenic Tfh cell population in infected mice by promoting apoptotic-like cell death. Finally, the P2X7 receptor was required to generate a balanced Th1/Tfh cell population with an improved ability to transfer parasite protection to CD4-deficient mice. This study provides a new insight into malaria immunology by showing the importance of P2X7 receptor in controlling the fine-tuning between Th1 and Tfh cell differentiation during P. chabaudi infection and thus in disease outcome.

  7. Differential Prediction of FAA Academy Performance on the Basis of Race and Written Air Traffic Control Specialist Aptitude Test Scores

    National Research Council Canada - National Science Library

    Broach, Dana

    1999-01-01

    The written air traffic control specialist (ATCS) aptitude test battery was evaluated for evidence of predictive bias within the framework of the Uniform Guidelines on Employee Selection Procedures (29 CFR 1607...

  8. Thermal dehydration of cobalt and zinc formate dihydrates by controlled-rate thermogravimetry (CRTG) and simultaneous X-ray diffractometry-differential scanning calorimetry (XRD-DSC)

    International Nuclear Information System (INIS)

    Arii, T.; Kishi, A.

    1999-01-01

    The thermal dehydration study of the similar hydrated salts, cobalt and zinc formate dihydrates, have been carried out successfully by means of X-ray diffractometry-differential scanning calorimetry (XRD-DSC) and controlled-rate thermogravimetry (CRTG). X-ray diffraction analysis recorded simultaneously indicates that the resulting anhydrous product, Zn(HCO 2 ) 2 , was crystalline, while Co(HCO 2 ) 2 was amorphous.The XRD-DSC data are proven to be invaluable in verifying the interpretation of overlapping processes in thermal events. In addition, these differences in the resulting anhydrous products can be explained from kinetic analysis results based on the CRTG data. The kinetic mechanism governing the dehydration of zinc formate dihydrate is a nucleation and growth process, while in the case of cobalt formate dihydrate a phase boundary controlled reaction is the governing mechanism. (Copyright (c) 1999 Elsevier Science B.V., Amsterdam. All rights reserved.)

  9. Constraint Differentiation

    DEFF Research Database (Denmark)

    Mödersheim, Sebastian Alexander; Basin, David; Viganò, Luca

    2010-01-01

    We introduce constraint differentiation, a powerful technique for reducing search when model-checking security protocols using constraint-based methods. Constraint differentiation works by eliminating certain kinds of redundancies that arise in the search space when using constraints to represent...... results show that constraint differentiation substantially reduces search and considerably improves the performance of OFMC, enabling its application to a wider class of problems....

  10. High-order tracking differentiator based adaptive neural control of a flexible air-breathing hypersonic vehicle subject to actuators constraints.

    Science.gov (United States)

    Bu, Xiangwei; Wu, Xiaoyan; Tian, Mingyan; Huang, Jiaqi; Zhang, Rui; Ma, Zhen

    2015-09-01

    In this paper, an adaptive neural controller is exploited for a constrained flexible air-breathing hypersonic vehicle (FAHV) based on high-order tracking differentiator (HTD). By utilizing functional decomposition methodology, the dynamic model is reasonably decomposed into the respective velocity subsystem and altitude subsystem. For the velocity subsystem, a dynamic inversion based neural controller is constructed. By introducing the HTD to adaptively estimate the newly defined states generated in the process of model transformation, a novel neural based altitude controller that is quite simpler than the ones derived from back-stepping is addressed based on the normal output-feedback form instead of the strict-feedback formulation. Based on minimal-learning parameter scheme, only two neural networks with two adaptive parameters are needed for neural approximation. Especially, a novel auxiliary system is explored to deal with the problem of control inputs constraints. Finally, simulation results are presented to test the effectiveness of the proposed control strategy in the presence of system uncertainties and actuators constraints. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

  11. Differential manifolds

    CERN Document Server

    Kosinski, Antoni A

    2007-01-01

    The concepts of differential topology form the center of many mathematical disciplines such as differential geometry and Lie group theory. Differential Manifolds presents to advanced undergraduates and graduate students the systematic study of the topological structure of smooth manifolds. Author Antoni A. Kosinski, Professor Emeritus of Mathematics at Rutgers University, offers an accessible approach to both the h-cobordism theorem and the classification of differential structures on spheres.""How useful it is,"" noted the Bulletin of the American Mathematical Society, ""to have a single, sho

  12. Modeling the Effects of Augmentation Strategies on the Control of Dengue Fever With an Impulsive Differential Equation.

    Science.gov (United States)

    Zhang, Xianghong; Tang, Sanyi; Cheke, Robert A; Zhu, Huaiping

    2016-10-01

    Dengue fever has rapidly become the world's most common vector-borne viral disease. Use of endosymbiotic Wolbachia is an innovative technology to prevent vector mosquitoes from reproducing and so break the cycle of dengue transmission. However, strategies such as population eradication and replacement will only succeed if appropriate augmentations with Wolbachia-infected mosquitoes that take account of a variety of factors are carried out. Here, we describe the spread of Wolbachia in mosquito populations using an impulsive differential system with four state variables, incorporating the effects of cytoplasmic incompatibility and the augmentation of Wolbachia-infected mosquitoes with different sex ratios. We then evaluated (a) how each parameter value contributes to the success of population replacement; (b) how different release quantities of infected mosquitoes with different sex ratios affect the success of population suppression or replacement; and (c) how the success of these two strategies can be realized to block the transmission of dengue fever. Analysis of the system's stability, bifurcations and sensitivity reveals the existence of forward and backward bifurcations, multiple attractors and the contribution of each parameter to the success of the strategies. The results indicate that the initial density of mosquitoes, the quantities of mosquitoes released in augmentations and their sex ratios have impacts on whether or not the strategies of population suppression or replacement can be achieved. Therefore, successful strategies rely on selecting suitable strains of Wolbachia and carefully designing the mosquito augmentation program.

  13. IgM and IgD B cell receptors differentially respond to endogenous antigens and control B cell fate

    Science.gov (United States)

    Noviski, Mark; Mueller, James L; Satterthwaite, Anne; Garrett-Sinha, Lee Ann; Brombacher, Frank

    2018-01-01

    Naive B cells co-express two BCR isotypes, IgM and IgD, with identical antigen-binding domains but distinct constant regions. IgM but not IgD is downregulated on autoreactive B cells. Because these isotypes are presumed to be redundant, it is unknown how this could impose tolerance. We introduced the Nur77-eGFP reporter of BCR signaling into mice that express each BCR isotype alone. Despite signaling strongly in vitro, IgD is less sensitive than IgM to endogenous antigen in vivo and developmental fate decisions are skewed accordingly. IgD-only Lyn−/− B cells cannot generate autoantibodies and short-lived plasma cells (SLPCs) in vivo, a fate thought to be driven by intense BCR signaling induced by endogenous antigens. Similarly, IgD-only B cells generate normal germinal center, but impaired IgG1+ SLPC responses to T-dependent immunization. We propose a role for IgD in maintaining the quiescence of autoreactive B cells and restricting their differentiation into autoantibody secreting cells. PMID:29521626

  14. A Tumor Suppressor Gene Product, Platelet-Derived Growth Factor Receptor-Like Protein Controls Chondrocyte Proliferation and Differentiation.

    Science.gov (United States)

    Kawata, Kazumi; Kubota, Satoshi; Eguchi, Takanori; Aoyama, Eriko; Moritani, Norifumi H; Oka, Morihiko; Kawaki, Harumi; Takigawa, Masaharu

    2017-11-01

    The platelet-derived growth factor receptor-like (PDGFRL) gene is regarded as a tumor suppressor gene. However, nothing is known about the molecular function of PDGFRL. In this study, we initially clarified its function in chondrocytes. Among all cell lines examined, the PDGFRL mRNA level was the highest in chondrocytic HCS-2/8 cells. Interestingly, the proliferation of chondrocytic HCS-2/8 cells was promoted by PDGFRL overexpression, whereas that of the breast cancer-derived MDA-MB-231 cells was inhibited. Of note, in PDGFRL-overexpressing HCS-2/8 cells, the expression of chondrocyte differentiation marker genes, SOX9, ACAN, COL2A1, COL10A1, and ALP, was decreased. Moreover, we confirmed the expression of PDGFRL mRNA in normal cartilage tissue and chondrocytes. Eventually, the expression of PDGFRL mRNA in condrocytes except in the case of hypertrophic chondrocytes was demonstrated in vivo and in vitro. These findings suggest that PDGFRL plays the different roles, depending upon cell types. Particularly, in chondrocytes, PDGFRL may play a new and important role which is distinct from the function previously reported. J. Cell. Biochem. 118: 4033-4044, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  15. Keep calm and share science!

    CERN Multimedia

    Antonella Del Rosso

    2015-01-01

    FameLab is the exciting competition for young researchers that is conquering the world of science communication. CERN, which was already a partner in the Swiss and French competitions, is now launching its own event. Enter the competition now!   FameLab is not just another talent show for scientists: its magic formula truly helps real scientists show off their communication skills. Successful candidates will have to impress the judges by giving an original and entertaining 3-minute talk.  In the words of one of the participants in the Swiss competition: “I enjoyed the fact that it wasn't only a competition, and there were also plenty of opportunities to network with other young researchers and to get valuable feedback on our public speaking and science communication skills.” The contestants are judged on the content, clarity and charisma of their talks. The result is an amazing collection of speeches that are inspiring, educational and accurate, despite their ...

  16. Childhood inhibitory control and adolescent impulsivity and novelty seeking as differential predictors of relational and overt aggression.

    Science.gov (United States)

    Sarkisian, Katherine; Van Hulle, Carol; Lemery-Chalfant, Kathryn; Goldsmith, H H

    2017-04-01

    Impulsivity is commonly conflated with novelty seeking, but these traits are conceptually independent and hold different predictive implications. Using a multi-informant, longitudinal design, we examined childhood inhibitory control, as well as adolescent impulsivity and novelty seeking, as predictors of aggression in a sample of 976 twins. Lower childhood inhibitory control and higher adolescent impulsivity predicted both overt and relational aggression in regression analyses that accounted for sex, puberty status, age, and socioeconomic status. As predicted, novelty seeking did not predict aggression, a finding that supports its independence from impulsivity.

  17. Differentiation of Serratia liquefaciens into swarm cells is controlled by the expression of the flhD master operon

    DEFF Research Database (Denmark)

    Eberl, L; Christiansen, Gunna; Molin, S

    1996-01-01

    The velocity with which a swarming colony of Serratia liquefaciens colonizes the surface of a suitable solid substratum was controlled by modulating the expression of the flhD master operon. In liquid medium, the stimulation of flhD expression resulted in filamentous, multinucleate, and hyperflag......The velocity with which a swarming colony of Serratia liquefaciens colonizes the surface of a suitable solid substratum was controlled by modulating the expression of the flhD master operon. In liquid medium, the stimulation of flhD expression resulted in filamentous, multinucleate...

  18. Dynamic QoS management in Differentiated Services using bandwidth brokers, RSVP aggregation and load control protocols

    NARCIS (Netherlands)

    Westberg, Lars; Eriksson, Anders; Karagiannis, Georgios; Heijenk, Geert; Rexhepi, Vlora; Partain, David

    2001-01-01

    A method and network subsystem for providing on demand end to end Quality of Service (Qos) in a dynamic manner, use a combination of Resource Reservation Protocol (RSVP), load control protocol (and its successors) and Bandwidth Brokers (BBs)(1106) which communicate using a predetermined protocol.

  19. Dynamic QoS management in Differentiated Services using bandwidth brokers, RSVP aggregation and load control protocols

    NARCIS (Netherlands)

    Westberg, Lars; Eriksson, Anders; Karagiannis, Georgios; Heijenk, Geert; Rexhepi, Vlora; Partain, David

    2009-01-01

    A method and network subsystem for providing on demand end to end Quality of Service (Qos) in a dynamic manner, use a combination of Resource Reservation Protocol (RSVP), load control protocol (and its successors) and Bandwidth Brokers (BBs)(1106) which communicate using a predetermined protocol.

  20. 1H-NMR METABONOMICS ANALYSIS OF SERA DIFFERENTIATES BETWEEN MAMMARY TUMOR-BEARING MICE AND HEALTHY CONTROLS

    Science.gov (United States)

    Global analysis of 1H-NMR spectra of serum is an appealing approach for the rapid detection of cancer. To evaluate the usefulness of this method in distinguishing between mammary tumor-bearing mice and healthy controls, we conducted 1H-NMR metabonomic analyses on serum samples ob...

  1. DIFFERENTIAL EXPRESSION OF GENES UNDER CONTROL OF THE MATING-TYPE GENES IN THE SECONDARY MYCELIUM OF SCHIZOPHYLLUM-COMMUNE

    NARCIS (Netherlands)

    ASGEIRSDOTTIR, SA; VANWETTER, MA; WESSELS, JGH

    The Schizophyllum commune SC3 gene, which encodes a hydrophobin that coats aerial hyphae, is expressed in both monokaryons and dikaryons. The dikaryons were formed by mating two monokaryons with different MATA and MATB genes, leading to activation of the MATA- and MATB-controlled pathways (MATA-on

  2. Asymptotic analysis and optimal control of an integro-differential system modelling healthy and cancer cells exposed to chemotherapy

    KAUST Repository

    Pouchol, Camille; Clairambault, Jean; Lorz, Alexander; Tré lat, Emmanuel

    2017-01-01

    to the treatment. We analyse the asymptotic behaviour of the model under constant infusion of drugs. By designing an appropriate Lyapunov function, we prove that both cell densities converge to Dirac masses. We then define an optimal control problem, by considering

  3. Characteristics That Differentiate Telecommuting from Non-Telecommuting Professionals in the Quality Assurance and Quality Control Arena

    Science.gov (United States)

    Claybon, Tina S.

    2013-01-01

    The interest in working from home in contrast to going to an office continues to be a growing phenomenon. This research examined personal characteristics of telecommuters and non-telecommuters including age, gender, years of working for the organization, and job satisfaction in the quality control and quality assurance arena. This study aimed to…

  4. Substance P Differentially Modulates Firing Rate of Solitary Complex (SC) Neurons from Control and Chronic Hypoxia-Adapted Adult Rats

    Science.gov (United States)

    Nichols, Nicole L.; Powell, Frank L.; Dean, Jay B.; Putnam, Robert W.

    2014-01-01

    NK1 receptors, which bind substance P, are present in the majority of brainstem regions that contain CO2/H+-sensitive neurons that play a role in central chemosensitivity. However, the effect of substance P on the chemosensitive response of neurons from these regions has not been studied. Hypoxia increases substance P release from peripheral afferents that terminate in the caudal nucleus tractus solitarius (NTS). Here we studied the effect of substance P on the chemosensitive responses of solitary complex (SC: NTS and dorsal motor nucleus) neurons from control and chronic hypoxia-adapted (CHx) adult rats. We simultaneously measured intracellular pH and electrical responses to hypercapnic acidosis in SC neurons from control and CHx adult rats using the blind whole cell patch clamp technique and fluorescence imaging microscopy. Substance P significantly increased the basal firing rate in SC neurons from control and CHx rats, although the increase was smaller in CHx rats. However, substance P did not affect the chemosensitive response of SC neurons from either group of rats. In conclusion, we found that substance P plays a role in modulating the basal firing rate of SC neurons but the magnitude of the effect is smaller for SC neurons from CHx adult rats, implying that NK1 receptors may be down regulated in CHx adult rats. Substance P does not appear to play a role in modulating the firing rate response to hypercapnic acidosis of SC neurons from either control or CHx adult rats. PMID:24516602

  5. Substance P differentially modulates firing rate of solitary complex (SC neurons from control and chronic hypoxia-adapted adult rats.

    Directory of Open Access Journals (Sweden)

    Nicole L Nichols

    Full Text Available NK1 receptors, which bind substance P, are present in the majority of brainstem regions that contain CO2/H(+-sensitive neurons that play a role in central chemosensitivity. However, the effect of substance P on the chemosensitive response of neurons from these regions has not been studied. Hypoxia increases substance P release from peripheral afferents that terminate in the caudal nucleus tractus solitarius (NTS. Here we studied the effect of substance P on the chemosensitive responses of solitary complex (SC: NTS and dorsal motor nucleus neurons from control and chronic hypoxia-adapted (CHx adult rats. We simultaneously measured intracellular pH and electrical responses to hypercapnic acidosis in SC neurons from control and CHx adult rats using the blind whole cell patch clamp technique and fluorescence imaging microscopy. Substance P significantly increased the basal firing rate in SC neurons from control and CHx rats, although the increase was smaller in CHx rats. However, substance P did not affect the chemosensitive response of SC neurons from either group of rats. In conclusion, we found that substance P plays a role in modulating the basal firing rate of SC neurons but the magnitude of the effect is smaller for SC neurons from CHx adult rats, implying that NK1 receptors may be down regulated in CHx adult rats. Substance P does not appear to play a role in modulating the firing rate response to hypercapnic acidosis of SC neurons from either control or CHx adult rats.

  6. Interference control in attention-deficit/hyperactivity disorder: differential Stroop effects for colour-naming versus counting

    NARCIS (Netherlands)

    Albrecht, B.; Rothenberger, A.; Sergeant, J.A.; Tannock, R.; Uebel, H.; Banaschewski, T.

    2008-01-01

    Deficits in interference control are ascribed to patients suffering from ADHD by a number of cognitive theories. However, previous research using the Stroop Colour Word Interference Task has demonstrated mixed results that may be explained by methodological issues (e.g., possible impact of colour

  7. Putative transcriptomic biomarkers in the inflammatory cytokine pathway differentiate major depressive disorder patients from control subjects and bipolar disorder patients.

    Directory of Open Access Journals (Sweden)

    Timothy R Powell

    Full Text Available Mood disorders consist of two etiologically related, but distinctly treated illnesses, major depressive disorder (MDD and bipolar disorder (BPD. These disorders share similarities in their clinical presentation, and thus show high rates of misdiagnosis. Recent research has revealed significant transcriptional differences within the inflammatory cytokine pathway between MDD patients and controls, and between BPD patients and controls, suggesting this pathway may possess important biomarker properties. This exploratory study attempts to identify disorder-specific transcriptional biomarkers within the inflammatory cytokine pathway, which can distinguish between control subjects, MDD patients and BPD patients. This is achieved using RNA extracted from subject blood and applying synthesized complementary DNA to quantitative PCR arrays containing primers for 87 inflammation-related genes. Initially, we use ANOVA to test for transcriptional differences in a 'discovery cohort' (total n = 90 and then we use t-tests to assess the reliability of any identified transcriptional differences in a 'validation cohort' (total n = 35. The two most robust and reliable biomarkers identified across both the discovery and validation cohort were Chemokine (C-C motif ligand 24 (CCL24 which was consistently transcribed higher amongst MDD patients relative to controls and BPD patients, and C-C chemokine receptor type 6 (CCR6 which was consistently more lowly transcribed amongst MDD patients relative to controls. Results detailed here provide preliminary evidence that transcriptional measures within inflammation-related genes might be useful in aiding clinical diagnostic decision-making processes. Future research should aim to replicate findings detailed in this exploratory study in a larger medication-free sample and examine whether identified biomarkers could be used prospectively to aid clinical diagnosis.

  8. Gene expression analysis of skin grafts and cultured keratinocytes using synthetic RNA normalization reveals insights into differentiation and growth control.

    Science.gov (United States)

    Katayama, Shintaro; Skoog, Tiina; Jouhilahti, Eeva-Mari; Siitonen, H Annika; Nuutila, Kristo; Tervaniemi, Mari H; Vuola, Jyrki; Johnsson, Anna; Lönnerberg, Peter; Linnarsson, Sten; Elomaa, Outi; Kankuri, Esko; Kere, Juha

    2015-06-25

    Keratinocytes (KCs) are the most frequent cells in the epidermis, and they are often isolated and cultured in vitro to study the molecular biology of the skin. Cultured primary cells and various immortalized cells have been frequently used as skin models but their comparability to intact skin has been questioned. Moreover, when analyzing KC transcriptomes, fluctuation of polyA+ RNA content during the KCs' lifecycle has been omitted. We performed STRT RNA sequencing on 10 ng samples of total RNA from three different sample types: i) epidermal tissue (split-thickness skin grafts), ii) cultured primary KCs, and iii) HaCaT cell line. We observed significant variation in cellular polyA+ RNA content between tissue and cell culture samples of KCs. The use of synthetic RNAs and SAMstrt in normalization enabled comparison of gene expression levels in the highly heterogenous samples and facilitated discovery of differences between the tissue samples and cultured cells. The transcriptome analysis sensitively revealed genes involved in KC differentiation in skin grafts and cell cycle regulation related genes in cultured KCs and emphasized the fluctuation of transcription factors and non-coding RNAs associated to sample types. The epidermal keratinocytes derived from tissue and cell culture samples showed highly different polyA+ RNA contents. The use of SAMstrt and synthetic RNA based normalization allowed the comparison between tissue and cell culture samples and thus proved to be valuable tools for RNA-seq analysis with translational approach. Transciptomics revealed clear difference both between tissue and cell culture samples and between primary KCs and immortalized HaCaT cells.

  9. Rigid dietary control, flexible dietary control, and intuitive eating: Evidence for their differential relationship to disordered eating and body image concerns.

    Science.gov (United States)

    Linardon, Jake; Mitchell, Sarah

    2017-08-01

    This study aimed to replicate and extend from Tylka, Calogero, and Daníelsdóttir (2015) findings by examining the relationship between rigid control, flexible control, and intuitive eating on various indices of disordered eating (i.e., binge eating, disinhibition) and body image concerns (i.e., shape and weight over-evaluation, body checking, and weight-related exercise motivations). This study also examined whether the relationship between intuitive eating and outcomes was mediated by dichotomous thinking and body appreciation. Analysing data from a sample of 372 men and women recruited through the community, this study found that, in contrast to rigid dietary control, intuitive eating uniquely and consistently predicted lower levels of disordered eating and body image concerns. This intuitive eating-disordered eating relationship was mediated by low levels of dichotomous thinking and the intuitive eating-body image relationship was mediated by high levels of body appreciation. Flexible control predicted higher levels of body image concerns and lower levels of disordered eating only when rigid control was accounted for. Findings suggest that until the adaptive properties of flexible control are further elucidated, it may be beneficial to promote intuitive eating within public health approaches to eating disorder prevention. In addition to this, particular emphasis should also be made toward promoting body acceptance and eradicating a dichotomous thinking style around food and eating. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. A Novel Scheme for Optimal Control of a Nonlinear Delay Differential Equations Model to Determine Effective and Optimal Administrating Chemotherapy Agents in Breast Cancer.

    Science.gov (United States)

    Ramezanpour, H R; Setayeshi, S; Akbari, M E

    2011-01-01

    Determining the optimal and effective scheme for administrating the chemotherapy agents in breast cancer is the main goal of this scientific research. The most important issue here is the amount of drug or radiation administrated in chemotherapy and radiotherapy for increasing patient's survival. This is because in these cases, the therapy not only kills the tumor cells, but also kills some of the healthy tissues and causes serious damages. In this paper we investigate optimal drug scheduling effect for breast cancer model which consist of nonlinear ordinary differential time-delay equations. In this paper, a mathematical model of breast cancer tumors is discussed and then optimal control theory is applied to find out the optimal drug adjustment as an input control of system. Finally we use Sensitivity Approach (SA) to solve the optimal control problem. The goal of this paper is to determine optimal and effective scheme for administering the chemotherapy agent, so that the tumor is eradicated, while the immune systems remains above a suitable level. Simulation results confirm the effectiveness of our proposed procedure. In this paper a new scheme is proposed to design a therapy protocol for chemotherapy in Breast Cancer. In contrast to traditional pulse drug delivery, a continuous process is offered and optimized, according to the optimal control theory for time-delay systems.

  11. Differential equations

    CERN Document Server

    Barbu, Viorel

    2016-01-01

    This textbook is a comprehensive treatment of ordinary differential equations, concisely presenting basic and essential results in a rigorous manner. Including various examples from physics, mechanics, natural sciences, engineering and automatic theory, Differential Equations is a bridge between the abstract theory of differential equations and applied systems theory. Particular attention is given to the existence and uniqueness of the Cauchy problem, linear differential systems, stability theory and applications to first-order partial differential equations. Upper undergraduate students and researchers in applied mathematics and systems theory with a background in advanced calculus will find this book particularly useful. Supplementary topics are covered in an appendix enabling the book to be completely self-contained.

  12. Differential calorimeter and temperature controller for stored energy measurements in irradiated alkali halides; Calorimetro diferencial y controlador de temperatura para medidas de energia almacenada en haluros alcalinos irradiados

    Energy Technology Data Exchange (ETDEWEB)

    Delgado Martinez, L

    1977-07-01

    The design and performance of a simple temperature-controlled differential calorimeter are presented. This system allows to measure radiation-induced stored energy in insulators, above room temperature with a differential thermal analysis method. With platelets of KC1 single crystals, the base lines obtained for T{sub 2} T{sub 1} (with T{sub 2}: irradiated sample temperature and T{sub 1}: reference sample temperature) show a smooth drift less of 0,2 degree centigree in the interval from 25 to 400 degree centigree. The discrepancy between two consecutive base lines is less than {+-} 0,02 degree centigree which implies a calorimeter sensitivity of about {+-}0,004 cal/g. This sensitivity allows to measure stored energy release in samples with a color center concentration low enough to be directly measured with a spectrophotometer so that a search for correlations among the features of the stored energy spectrum and the color center annealing can be made. (Author) 13 refs.

  13. An atmospheric dispersion model for linear sources in calm wind, stable conditions; Un modello di dispersione atmosferica per sorgenti lineari in condizioni di vento debole

    Energy Technology Data Exchange (ETDEWEB)

    Cirillo, M. C. [ENEA, Centro Ricerche Casaccia, Rome (Italy). Dipt. Ambiente; Buratti, D. [Rome Univ. La Sapienza, Rome (Italy). Facolta' di Scienze Statistiche; Metallo, M. C.; Poli, A.A. [ESA s.a.s., Bracciano, RM (Italy)

    1999-07-01

    In this report a dispersion model is proposed that provides an estimate of concentration of gaseous pollutants emitted by an highway, or in general by a line source, in presence of low wind speed. This aim was pursued because available models have not a satisfactory behaviour in such conditions, which is critical for dispersion of gaseous pollutants. This lack is due to difficulty of simulating dispersion turbulent component which is determined by fluctuation of wind speed and wind direction, and in presence of calm conditions it assumes values comparable with transport component. The proposed model overcomes this difficulty, as it is shown by sensitivity analysis and comparison with experimental data. The capability of simulating dispersion eve in critical conditions, like the presence of low level inversion, and the absence of source geometrical approximations make the model a tool that, properly used, may contribute to the efficient planning and management of environmental resources. [Italian] In questo rapporto viene proposto un modello per la stima delle concentrazioni di inquinanti aeriformi emessi da un'arteria stradale, o in generale da una sorgente lineare, in presenza di vento debole. Questo scopo e' stato perseguito in quanto in questa condizione, nonostante la dispersione degli inquinanti risulti fortemente problematica, i modelli disponibili in letteratura non hanno un comportamento soddisfacente. Questa mancanca e' attribuibile alla difficolta' di simulare la componente turbolenta della dispersione, dovuta alla fluttuazione della direzione e della velocita' del vento che, in presenza di vento debole, assume valori confrontabili alla componente di trasporto. Il modello qui di seguito proposto supera questa difficolta', come dimostrano l'analisi di sensibilita' e il confronto con un caso reale; la capacita' di simulare la dispersione anche in condizioni fisicamente critiche quali la presenza di inversione a

  14. Multiple sclerosis: microRNA expression profiles accurately differentiate patients with relapsing-remitting disease from healthy controls.

    Directory of Open Access Journals (Sweden)

    Andreas Keller

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory demyelinating disease of the central nervous system, which is heterogenous with respect to clinical manifestations and response to therapy. Identification of biomarkers appears desirable for an improved diagnosis of MS as well as for monitoring of disease activity and treatment response. MicroRNAs (miRNAs are short non-coding RNAs, which have been shown to have the potential to serve as biomarkers for different human diseases, most notably cancer. Here, we analyzed the expression profiles of 866 human miRNAs. In detail, we investigated the miRNA expression in blood cells of 20 patients with relapsing-remitting MS (RRMS and 19 healthy controls using a human miRNA microarray and the Geniom Real Time Analyzer (GRTA platform. We identified 165 miRNAs that were significantly up- or downregulated in patients with RRMS as compared to healthy controls. The best single miRNA marker, hsa-miR-145, allowed discriminating MS from controls with a specificity of 89.5%, a sensitivity of 90.0%, and an accuracy of 89.7%. A set of 48 miRNAs that was evaluated by radial basis function kernel support vector machines and 10-fold cross validation yielded a specificity of 95%, a sensitivity of 97.6%, and an accuracy of 96.3%. While 43 of the 165 miRNAs deregulated in patients with MS have previously been related to other human diseases, the remaining 122 miRNAs are so far exclusively associated with MS. The implications of our study are twofold. The miRNA expression profiles in blood cells may serve as a biomarker for MS, and deregulation of miRNA expression may play a role in the pathogenesis of MS.

  15. Differential effects of plant species on a mite pest (Tetranychus utricae) and its predator (Phytoseiulus persimilis): implications for biological control.

    Science.gov (United States)

    Skirvin, D J; de Courcy Williams, M

    1999-06-01

    The influence of plant species on the population dynamics of the spider mite pest, Tetranychus urticae, and its predator, Phytoseiulus persimilis, was examined as a prerequisite to effective biological control on ornamental nursery stock. Experiments have been done to investigate how the development, fecundity and movement of T. urticae, and the movement of P. persimilis were affected by plant species. A novel experimental method, which incorporates plant structure, was used to investigate the functional response of P. persimilis. Development times for T. urticae were consistent with published data and did not differ with plant species in a biologically meaningful way. Plant species was shown to have a major influence on fecundity (P < 0.001) and movement of the pest mite (P < 0.01), but no influence on the movement of the predator. The movement of both pest and predator was shown to be related to the density of the adult pest mites on the plant (P < 0.001). Plant structure affected the functional response, particularly in relation to the ability of the predator to locate prey at low densities. The impact of these findings on the effective use of biological control on ornamental nursery stock is discussed.

  16. Differential physiological responses of dalmatian toadflax, Linaria dalmatica L. Miller, to injury from two insect biological control agents: Implications for decision-making in biological control

    Science.gov (United States)

    Robert K. D. Peterson; Sharlene E. Sing; David K. Weaver

    2005-01-01

    Successful biological control of invasive weeds with specialist herbivorous insects is predicated on the assumption that the injury stresses the weeds sufficiently to cause reductions in individual fitness. Because plant gas exchange directly impacts growth and fitness, characterizing how injury affects these primary processes may provide a key indicator of...

  17. Differential games

    CERN Document Server

    Friedman, Avner

    2006-01-01

    This volume lays the mathematical foundations for the theory of differential games, developing a rigorous mathematical framework with existence theorems. It begins with a precise definition of a differential game and advances to considerations of games of fixed duration, games of pursuit and evasion, the computation of saddle points, games of survival, and games with restricted phase coordinates. Final chapters cover selected topics (including capturability and games with delayed information) and N-person games.Geared toward graduate students, Differential Games will be of particular interest

  18. Effective genetic modification and differentiation of hMSCs upon controlled release of rAAV vectors using alginate/poloxamer composite systems.

    Science.gov (United States)

    Díaz-Rodríguez, P; Rey-Rico, A; Madry, H; Landin, M; Cucchiarini, M

    2015-12-30

    Viral vectors are common tools in gene therapy to deliver foreign therapeutic sequences in a specific target population via their natural cellular entry mechanisms. Incorporating such vectors in implantable systems may provide strong alternatives to conventional gene transfer procedures. The goal of the present study was to generate different hydrogel structures based on alginate (AlgPH155) and poloxamer PF127 as new systems to encapsulate and release recombinant adeno-associated viral (rAAV) vectors. Inclusion of rAAV in such polymeric capsules revealed an influence of the hydrogel composition and crosslinking temperature upon the vector release profiles, with alginate (AlgPH155) structures showing the fastest release profiles early on while over time vector release was more effective from AlgPH155+PF127 [H] capsules crosslinked at a high temperature (50°C). Systems prepared at room temperature (AlgPH155+PF127 [C]) allowed instead to achieve a more controlled release profile. When tested for their ability to target human mesenchymal stem cells, the different systems led to high transduction efficiencies over time and to gene expression levels in the range of those achieved upon direct vector application, especially when using AlgPH155+PF127 [H]. No detrimental effects were reported on either cell viability or on the potential for chondrogenic differentiation. Inclusion of PF127 in the capsules was also capable of delaying undesirable hypertrophic cell differentiation. These findings are of promising value for the further development of viral vector controlled release strategies. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. A differentiating empirical linguistic analysis of dreamer activity in reports of EEG-controlled REM-dreams and hypnagogic hallucinations.

    Science.gov (United States)

    Speth, Jana; Frenzel, Clemens; Voss, Ursula

    2013-09-01

    We present Activity Analysis as a new method for the quantification of subjective reports of altered states of consciousness with regard to the indicated level of simulated motor activity. Empirical linguistic activity analysis was conducted with dream reports conceived immediately after EEG-controlled periods of hypnagogic hallucinations and REM-sleep in the sleep laboratory. Reports of REM-dreams exhibited a significantly higher level of simulated physical dreamer activity, while hypnagogic hallucinations appear to be experienced mostly from the point of passive observer. This study lays the groundwork for clinical research on the level of simulated activity in pathologically altered states of subjective experience, for example in the REM-dreams of clinically depressed patients, or in intrusions and dreams of patients diagnosed with PTSD. Copyright © 2013 Elsevier Inc. All rights reserved.

  20. Osteoarthritis: Control of human cartilage hypertrophic differentiation. Research highlight van: Gremlin1, frizzled-related protein, and Dkk-1 are key regulators of human articular cartilage homeostasis

    NARCIS (Netherlands)

    Buckland, J.; Leijten, Jeroen Christianus Hermanus; van Blitterswijk, Clemens; Karperien, Hermanus Bernardus Johannes

    2012-01-01

    Disruption of articular cartilage homeostasis is important in osteoarthritis (OA) pathogenesis, key to which is activation of articular chondrocyte hypertrophic differentiation. Healthy articular cartilage is resistant to hypertrophic differentiation, whereas growth-plate cartilage is destined to

  1. Distinct coping strategies differentially predict urge levels and lapses in a smoking cessation attempt.

    Science.gov (United States)

    Brodbeck, Jeannette; Bachmann, Monica S; Znoj, Hansjörg

    2013-06-01

    This study analysed mechanisms through which stress-coping and temptation-coping strategies were associated with lapses. Furthermore, we explored whether distinct coping strategies differentially predicted reduced lapse risk, lower urge levels, or a weaker association between urge levels and lapses during the first week of an unassisted smoking cessation attempt. Participants were recruited via the internet and mass media in Switzerland. Ecological momentary assessment (EMA) with mobile devices was used to assess urge levels and lapses. Online questionnaires were used to measure smoking behaviours and coping variables at baseline, as well as smoking behaviour at the three-month follow-up. The sample consisted of 243 individuals, aged 20 to 40, who reported 4199 observations. Findings of multilevel regression analyses show that coping was mainly associated with a reduced lapse risk and not with lower urge levels or a weaker association between urge levels and lapses. 'Calming down' and 'commitment to change' predicted a lower lapse risk and also a weaker relation between urge levels and lapses. 'Stimulus control' predicted a lower lapse risk and lower urge levels. Conversely, 'task-orientation' and 'risk assessment' were related to higher lapse risk and 'risk assessment' also to higher urge levels. Disengagement coping i.e. 'eating or shopping', 'distraction', and 'mobilising social support' did not affect lapse risk. Promising coping strategies during the initial stage of smoking cessation attempt are targeted directly at reducing the lapse risk and are characterised by engagement with the stressor or one's reactions towards the stressor and a focus on positive consequences instead of health risks. Copyright © 2013 Elsevier Ltd. All rights reserved.

  2. Terminal Differentiation of Adult Hippocampal Progenitor Cells Is a Step Functionally Dissociable from Proliferation and Is Controlled by Tis21, Id3 and NeuroD2

    OpenAIRE

    Laura Micheli; Manuela Ceccarelli; Roberta Gioia; Giorgio D’Andrea; Stefano Farioli-Vecchioli; Marco Costanzi; Daniele Saraulli; Daniele Saraulli; Vincenzo Cestari; Felice Tirone

    2017-01-01

    Cell proliferation and differentiation are interdependent processes. Here, we have asked to what extent the two processes of neural progenitor cell amplification and differentiation are functionally separated. Thus, we analyzed whether it is possible to rescue a defect of terminal differentiation in progenitor cells of the dentate gyrus, where new neurons are generated throughout life, by inducing their proliferation and/or their differentiation with different stimuli appropriately timed. As ...

  3. Differential Geometry

    CERN Document Server

    Stoker, J J

    2011-01-01

    This classic work is now available in an unabridged paperback edition. Stoker makes this fertile branch of mathematics accessible to the nonspecialist by the use of three different notations: vector algebra and calculus, tensor calculus, and the notation devised by Cartan, which employs invariant differential forms as elements in an algebra due to Grassman, combined with an operation called exterior differentiation. Assumed are a passing acquaintance with linear algebra and the basic elements of analysis.

  4. Some New Trends in Differential Equations

    Indian Academy of Sciences (India)

    Mythily Ramaswamy TIFR Centre for Applicable Mathematics, Bangalore

    2008-04-05

    Apr 5, 2008 ... Optimal Control Problems. Controllability. Stabilizability. Overview. 1 Differential Equations as Models. Mathematical Models. Brief History. Main Questions. 2 Optimal Control Problems. Mathematical Model. Optimal Control. Dynamic Programming. Pontryagin Maximum Principle. 3 Controllability. A Model.

  5. Differential effect of amylin on endothelial-dependent vasodilation in mesenteric arteries from control and insulin resistant rats.

    Directory of Open Access Journals (Sweden)

    Mariam El Assar

    Full Text Available Insulin resistance (IR is frequently associated with endothelial dysfunction and has been proposed to play a major role in cardiovascular disease (CVD. On the other hand, amylin has long been related to IR. However the role of amylin in the vascular dysfunction associated to IR is not well addressed. Therefore, the aim of the study was to assess the effect of acute treatment with amylin on endothelium-dependent vasodilation of isolated mesenteric arteries from control (CR and insulin resistant (IRR rats and to evaluate the possible mechanisms involved. Five week-old male Wistar rats received 20% D-fructose dissolved in drinking water for 8 weeks and were compared with age-matched CR. Plasmatic levels of glucose, insulin and amylin were measured. Mesenteric microvessels were dissected and mounted in wire myographs to evaluate endothelium-dependent vasodilation to acetylcholine. IRR displayed a significant increase in plasmatic levels of glucose, insulin and amylin and reduced endothelium-dependent relaxation when compared to CR. Acute treatment of mesenteric arteries with r-amylin (40 pM deteriorated endothelium-dependent responses in CR. Amylin-induced reduction of endothelial responses was unaffected by the H2O2 scavenger, catalase, but was prevented by the extracellular superoxide scavenger, superoxide dismutase (SOD or the NADPH oxidase inhibitor (VAS2870. By opposite, amylin failed to further inhibit the impaired relaxation in mesenteric arteries of IRR. SOD, or VAS2870, but not catalase, ameliorated the impairment of endothelium-dependent relaxation in IRR. At concentrations present in insulin resistance conditions, amylin impairs endothelium-dependent vasodilation in mircrovessels from rats with preserved vascular function and low levels of endogenous amylin. In IRR with established endothelial dysfunction and elevated levels of amylin, additional exposure to this peptide has no effect on endothelial vasodilation. Increased superoxide

  6. Npn-1 contributes to axon-axon interactions that differentially control sensory and motor innervation of the limb.

    Directory of Open Access Journals (Sweden)

    Rosa-Eva Huettl

    2011-02-01

    Full Text Available The initiation, execution, and completion of complex locomotor behaviors are depending on precisely integrated neural circuitries consisting of motor pathways that activate muscles in the extremities and sensory afferents that deliver feedback to motoneurons. These projections form in tight temporal and spatial vicinities during development, yet the molecular mechanisms and cues coordinating these processes are not well understood. Using cell-type specific ablation of the axon guidance receptor Neuropilin-1 (Npn-1 in spinal motoneurons or in sensory neurons in the dorsal root ganglia (DRG, we have explored the contribution of this signaling pathway to correct innervation of the limb. We show that Npn-1 controls the fasciculation of both projections and mediates inter-axonal communication. Removal of Npn-1 from sensory neurons results in defasciculation of sensory axons and, surprisingly, also of motor axons. In addition, the tight coupling between these two heterotypic axonal populations is lifted with sensory fibers now leading the spinal nerve projection. These findings are corroborated by partial genetic elimination of sensory neurons, which causes defasciculation of motor projections to the limb. Deletion of Npn-1 from motoneurons leads to severe defasciculation of motor axons in the distal limb and dorsal-ventral pathfinding errors, while outgrowth and fasciculation of sensory trajectories into the limb remain unaffected. Genetic elimination of motoneurons, however, revealed that sensory axons need only minimal scaffolding by motor axons to establish their projections in the distal limb. Thus, motor and sensory axons are mutually dependent on each other for the generation of their trajectories and interact in part through Npn-1-mediated fasciculation before and within the plexus region of the limbs.

  7. Differential control of ageing and lifespan by isoforms and splice variants across the mTOR network.

    Science.gov (United States)

    Razquin Navas, Patricia; Thedieck, Kathrin

    2017-07-15

    Ageing can be defined as the gradual deterioration of physiological functions, increasing the incidence of age-related disorders and the probability of death. Therefore, the term ageing not only reflects the lifespan of an organism but also refers to progressive functional impairment and disease. The nutrient-sensing kinase mTOR (mammalian target of rapamycin) is a major determinant of ageing. mTOR promotes cell growth and controls central metabolic pathways including protein biosynthesis, autophagy and glucose and lipid homoeostasis. The concept that mTOR has a crucial role in ageing is supported by numerous reports on the lifespan-prolonging effects of the mTOR inhibitor rapamycin in invertebrate and vertebrate model organisms. Dietary restriction increases lifespan and delays ageing phenotypes as well and mTOR has been assigned a major role in this process. This may suggest a causal relationship between the lifespan of an organism and its metabolic phenotype. More than 25 years after mTOR's discovery, a wealth of metabolic and ageing-related effects have been reported. In this review, we cover the current view on the contribution of the different elements of the mTOR signalling network to lifespan and age-related metabolic impairment. We specifically focus on distinct roles of isoforms and splice variants across the mTOR network. The comprehensive analysis of mouse knockout studies targeting these variants does not support a tight correlation between lifespan prolongation and improved metabolic phenotypes and questions the strict causal relationship between them. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  8. Traditional Chinese medicine for stable angina pectoris via TCM pattern differentiation and TCM mechanism: study protocol of a randomized controlled trial.

    Science.gov (United States)

    Zhang, Zhe; Zhang, Fan; Wang, Yang; Du, Yi; Zhang, Huiyong; Kong, Dezhao; Liu, Yue; Yang, Guanlin

    2014-10-30

    Stable angina pectoris is experienced as trans-sternal or retro-sternal pressure or pain that may radiate to the left arm, neck or back. Although available evidence relating to its effectiveness and mechanism are weak, traditional Chinese medicine is used as an alternative therapy for stable angina pectoris. We report a protocol of a randomized controlled trial using traditional Chinese medicine to investigate the effectiveness, mechanism and safety for patients with stable angina pectoris. This is a north-east Chinese, multi-center, multi-blinded, placebo-controlled and superiority randomized trail. A total of 240 patients with stable angina pectoris will be randomly assigned to three groups: two treatment groups and a control group. The treatment groups will receive Chinese herbal medicine consisting of Yi-Qi-Jian-Pi and Qu-Tan-Hua-Zhuo granule and Yi-Qi-Jian-Pi and Qu-Tan-Hua-Yu granule, respectively, and conventional medicine. The control group will receive placebo medicine in addition to conventional medicine. All 3 groups will undergo a 12-week treatment and 2-week follow-up. Four visits in sum will be scheduled for each subject: 1 visit each in week 0, week 4, week 12 and week 14. The primary outcomes include: the frequency of angina pectoris attack; the dosage of nitroglycerin; body limited dimension of Seattle Angina Questionnaire. The secondary outcomes include: except for the body limited dimension of SAQ, traditional Chinese medicine pattern questionnaire and so on. Therapeutic mechanism outcomes, safety outcomes and endpoint outcomes will be also assessed. The primary aim of this trial is to develop a standard protocol to utilize high-quality EBM evidence for assessing the effectiveness and safety of SAP via TCM pattern differentiation as well as exploring the efficacy mechanism and regulation with the molecular biology and systems biology. ChiCTR-TRC-13003608, registered 18 June 2013.

  9. Differential control of Yersinia pestis biofilm formation in vitro and in the flea vector by two c-di-GMP diguanylate cyclases.

    Directory of Open Access Journals (Sweden)

    Yi-Cheng Sun

    2011-04-01

    Full Text Available Yersinia pestis forms a biofilm in the foregut of its flea vector that promotes transmission by flea bite. As in many bacteria, biofilm formation in Y. pestis is controlled by intracellular levels of the bacterial second messenger c-di-GMP. Two Y. pestis diguanylate cyclase (DGC enzymes, encoded by hmsT and y3730, and one phosphodiesterase (PDE, encoded by hmsP, have been shown to control biofilm production in vitro via their opposing c-di-GMP synthesis and degradation activities, respectively. In this study, we provide further evidence that hmsT, hmsP, and y3730 are the only three genes involved in c-di-GMP metabolism in Y. pestis and evaluated the two DGCs for their comparative roles in biofilm formation in vitro and in the flea vector. As with HmsT, the DGC activity of Y3730 depended on a catalytic GGDEF domain, but the relative contribution of the two enzymes to the biofilm phenotype was influenced strongly by the environmental niche. Deletion of y3730 had a very minor effect on in vitro biofilm formation, but resulted in greatly reduced biofilm formation in the flea. In contrast, the predominant effect of hmsT was on in vitro biofilm formation. DGC activity was also required for the Hms-independent autoaggregation phenotype of Y. pestis, but was not required for virulence in a mouse model of bubonic plague. Our results confirm that only one PDE (HmsP and two DGCs (HmsT and Y3730 control c-di-GMP levels in Y. pestis, indicate that hmsT and y3730 are regulated post-transcriptionally to differentially control biofilm formation in vitro and in the flea vector, and identify a second c-di-GMP-regulated phenotype in Y. pestis.

  10. The progesterone receptor antagonist, onapristone has differential effects on the timing and control of the luteolytic mechanism depending on timing of administration in sheep.

    Science.gov (United States)

    Mann, G E; Wathes, D C; Robinson, R S

    2013-08-25

    Cyclic ewes were treated with control vehicle or progesterone receptor antagonist (onapristone; 100mg i.m. twice daily) during either early (day 3-5) or late (day 12-14) luteal phase and plasma samples collected for hormone analysis and to determine endogenous and oxytocin induced PGF2α release. On day 14 and 17, ewes were euthanised and reproductive tracts collected for ovarian morphology and endometrium for oxytoxin and steroid hormone receptor analysis. Early treatment increased LH, but not progesterone or oestradiol, while late treatment elevated all three hormones. Early treatment delayed the up-regulation of endometrial oxytocin receptors and responsiveness to oxytocin challenge, delaying luteolysis. Late treatment advanced development of oxytocin receptors and responsiveness to oxytocin though not timing of luteolysis. Patterns of hormone receptor mRNA were differentially disrupted by treatments. Results provide mechanistic insight into hormonal control of the oestrous cycle and identify the ability of the luteolytic mechanism to dissociate from functional luteolysis. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  11. A Randomized Controlled Trial for the Effectiveness of Aromatherapy in Decreasing Salivary Gland Damage following Radioactive Iodine Therapy for Differentiated Thyroid Cancer.

    Science.gov (United States)

    Nakayama, Michihiro; Okizaki, Atsutaka; Takahashi, Koji

    2016-01-01

    Objective. The aim of this study was to investigate effects of aromatherapy in decreasing salivary gland damage for patients undergoing radioactive iodine (RAI) therapy with differentiated thyroid cancer (DTC). Materials and Methods. The subjects were 71 patients with DTC. They were divided into aromatherapy group (group A, n = 35) and a control group (group B, n = 36). We blended 1.0 mL of lemon and 0.5 mL of ginger essential oils. The patients in the inhalation aromatherapy group inhaled this blend oil and those in the control group inhaled distilled water as placebo for 10 min during admission. We statistically compared salivary gland function before and after treatment between groups A and B. Results. In comparison with group B, the rate of change of the accumulation rate was significantly higher in the parotid glands and submandibular glands of group A ( P aromatherapy in the prevention of treatment-related salivary gland disorder. This trial is registered with UMIN Clinical Trial Registry: UMIN000013968.

  12. A Randomized Controlled Trial for the Effectiveness of Aromatherapy in Decreasing Salivary Gland Damage following Radioactive Iodine Therapy for Differentiated Thyroid Cancer

    Directory of Open Access Journals (Sweden)

    Michihiro Nakayama

    2016-01-01

    Full Text Available Objective. The aim of this study was to investigate effects of aromatherapy in decreasing salivary gland damage for patients undergoing radioactive iodine (RAI therapy with differentiated thyroid cancer (DTC. Materials and Methods. The subjects were 71 patients with DTC. They were divided into aromatherapy group (group A, n=35 and a control group (group B, n=36. We blended 1.0 mL of lemon and 0.5 mL of ginger essential oils. The patients in the inhalation aromatherapy group inhaled this blend oil and those in the control group inhaled distilled water as placebo for 10 min during admission. We statistically compared salivary gland function before and after treatment between groups A and B. Results. In comparison with group B, the rate of change of the accumulation rate was significantly higher in the parotid glands and submandibular glands of group A (P<0.05. In comparison with group B, a significant increase in rate of secretion change before and after treatment was noted in the bilateral parotid glands in group A (P<0.05. Conclusion. Because an amelioration of salivary gland function was observed in the present study, our results suggest the efficacy of aromatherapy in the prevention of treatment-related salivary gland disorder. This trial is registered with UMIN Clinical Trial Registry: UMIN000013968.

  13. The differential effects of core stabilization exercise regime and conventional physiotherapy regime on postural control parameters during perturbation in patients with movement and control impairment chronic low back pain

    Directory of Open Access Journals (Sweden)

    Fernandes Svetlana

    2010-05-01

    Full Text Available Abstract Background The purpose of the present study was to examine the differential effect of core stability exercise training and conventional physiotherapy regime on altered postural control parameters in patients with chronic low back pain (CLBP. As heterogeneity in CLBP population moderates the effect of intervention on outcomes, in this study, interventions approaches were used based on sub-groups of CLBP. Methods This was an allocation concealed, blinded, sequential and pragmatic control trial. Three groups of participants were investigated during postural perturbations: 1 CLBP patients with movement impairment (n = 15, MI group randomized to conventional physiotherapy regime 2 fifteen CLBP patients with control impairment randomized to core stability group (CI group and 3 fifteen healthy controls (HC. Results The MI group did not show any significant changes in postural control parameters after the intervention period however they improved significantly in disability scores and fear avoidance belief questionnaire work score (P 0.8 after 8 weeks of core stability exercises for the adjusted p values. Postural control parameters of HC group were analyzed independently with pre and post postural control parameters of CI and MI group. This revealed the significant improvements in postural control parameters in CI group compared to MI group indicating the specific adaptation to the core stability exercises in CI group. Though the disability scores were reduced significantly in CI and MI groups (p Conclusions In this study core stability exercise group demonstrated significant improvements after intervention in ground reaction forces (Fz, Mz; g > 0.8 indicating changes in load transfer patterns during perturbation similar to HC group. Trial registration UTRN095032158-06012009423714

  14. Pooled analysis of two case-control studies in New Caledonia and French Polynesia of body mass index and differentiated thyroid cancer: the importance of body surface area.

    Science.gov (United States)

    Cléro, Enora; Leux, Christophe; Brindel, Pauline; Truong, Thérèse; Anger, Antoinette; Teinturier, Cécile; Diallo, Ibrahima; Doyon, Françoise; Guénel, Pascal; de Vathaire, Florent

    2010-11-01

    New Caledonia and French Polynesia have among of the world highest thyroid cancer incidence rates. Studies have demonstrated a relationship between anthropometric parameters and the prevalence of cancer. In this study we evaluated further the relationship between body mass index (BMI) and other anthropometric parameters on the incidence of thyroid cancer in the New Caledonia and French Polynesia populations. We performed a pooled analysis of two case-control studies in New Caledonia and French Polynesia. We included a total of 554 cases (65 men and 489 women) of differentiated thyroid cancers and 776 population control subjects matched on sex, age, and study. Anthropometric factors (height, weight, BMI, body fat percentage [BF%], and body surface area [BSA]), at age 18 and before diagnosis, were analyzed by conditional logistic regression, adjusting for other independent risk factors. A high proportion of cases (73%) were overweight (25-29.9 kg/m(2)) or obese (≥30 kg/m(2)) before diagnosis of thyroid cancer (against 57% of control subjects). An increased risk of thyroid cancer was observed with greater height, weight, BMI, BF%, and BSA. The association of thyroid cancer risk with height, weight, BMI, and BF% did not remain when adjustment was made for BSA. By comparison, the odds ratios for the highest versus the lowest quartile of BSA at age 18 were 3.97 (95% confidence interval, 2.57-6.15; p < 0.001) for women and 4.06 (95% confidence interval, 1.03-16.06; p = 0.04) for men. The association between thyroid cancer risk and each of anthropometric factors did not depend on tumor size or menopausal status before diagnosis. Among anthropometric factors, BSA plays a dominant role in thyroid cancer risk and explains the apparent role of BMI.

  15. (SWASH-D for Worms: A pilot study investigating the differential impact of school- versus community-based integrated control programs for soil-transmitted helminths.

    Directory of Open Access Journals (Sweden)

    Naomi E Clarke

    2018-05-01

    Full Text Available Soil-transmitted helminths (STH infect nearly 1.5 billion individuals globally, and contribute to poor physical and cognitive development in children. STH control programs typically consist of regular delivery of anthelminthic drugs, targeting school-aged children. Expanding STH control programs community-wide may improve STH control among school-aged children, and combining deworming with improvements to water, sanitation and hygiene (WASH may further reduce transmission. The (SWASH-D for Worms pilot study aims to compare the differential impact of integrated WASH and deworming programs when implemented at primary schools only versus when additionally implemented community-wide.A two-arm, non-randomized cluster intervention study was conducted. Six communities were identified by partner WASH agencies and enrolled in the study. All communities received a school-based WASH and deworming program, while three additionally received a community-based WASH and deworming program. STH infections were measured in school-aged children at baseline and six months after deworming. Over 90% of eligible children were recruited for the study, of whom 92.3% provided stool samples at baseline and 88.9% at follow-up. The school WASH intervention improved school sanitation, while the community WASH intervention reduced open defecation from 50.4% (95% CI 41.8-59.0 to 23.5% (95% CI 16.7-32.0. There was a trend towards reduced odds of N. americanus infection among children who received the community-wide intervention (OR 0.42, 95% CI 0.07-2.36, p = 0.32.This pilot study provides proof of principle for testing the hypothesis that community-wide STH control programs have a greater impact on STH infections among children than school-based programs, and supports the rationale for conducting a full-scale cluster randomized controlled trial. High recruitment and participation rates and successful implementation of school WASH programs demonstrate study feasibility and

  16. Transcriptional networks controlling adipocyte differentiation

    DEFF Research Database (Denmark)

    Siersbæk, R; Mandrup, Susanne

    2011-01-01

    " of the transcription factor networks operating at specific time points during adipogenesis. Using such global "snapshots," we have demonstrated that dramatic remodeling of the chromatin template occurs within the first few hours following adipogenic stimulation and that many of the early transcription factors bind...... in a cooperative fashion to transcription factor hotspots. Such hotspots are likely to represent key chromatin nodes, where many adipogenic signaling pathways converge to drive the adipogenic transcriptional reprogramming....

  17. Comparison of Control Approaches in Genetic Regulatory Networks by Using Stochastic Master Equation Models, Probabilistic Boolean Network Models and Differential Equation Models and Estimated Error Analyzes

    Science.gov (United States)

    Caglar, Mehmet Umut; Pal, Ranadip

    2011-03-01

    Central dogma of molecular biology states that ``information cannot be transferred back from protein to either protein or nucleic acid''. However, this assumption is not exactly correct in most of the cases. There are a lot of feedback loops and interactions between different levels of systems. These types of interactions are hard to analyze due to the lack of cell level data and probabilistic - nonlinear nature of interactions. Several models widely used to analyze and simulate these types of nonlinear interactions. Stochastic Master Equation (SME) models give probabilistic nature of the interactions in a detailed manner, with a high calculation cost. On the other hand Probabilistic Boolean Network (PBN) models give a coarse scale picture of the stochastic processes, with a less calculation cost. Differential Equation (DE) models give the time evolution of mean values of processes in a highly cost effective way. The understanding of the relations between the predictions of these models is important to understand the reliability of the simulations of genetic regulatory networks. In this work the success of the mapping between SME, PBN and DE models is analyzed and the accuracy and affectivity of the control policies generated by using PBN and DE models is compared.

  18. Genetic Control of Lyme Arthritis by Borrelia burgdorferi Arthritis-Associated Locus 1 Is Dependent on Localized Differential Production of IFN-β and Requires Upregulation of Myostatin.

    Science.gov (United States)

    Paquette, Jackie K; Ma, Ying; Fisher, Colleen; Li, Jinze; Lee, Sang Beum; Zachary, James F; Kim, Yong Soo; Teuscher, Cory; Weis, Janis J

    2017-11-15

    Previously, using a forward genetic approach, we identified differential expression of type I IFN as a positional candidate for an expression quantitative trait locus underlying Borrelia burgdorferi arthritis-associated locus 1 ( Bbaa1 ). In this study, we show that mAb blockade revealed a unique role for IFN-β in Lyme arthritis development in B6.C3- Bbaa1 mice. Genetic control of IFN-β expression was also identified in bone marrow-derived macrophages stimulated with B. burgdorferi , and it was responsible for feed-forward amplification of IFN-stimulated genes. Reciprocal radiation chimeras between B6.C3- Bbaa1 and C57BL/6 mice revealed that arthritis is initiated by radiation-sensitive cells, but orchestrated by radiation-resistant components of joint tissue. Advanced congenic lines were developed to reduce the physical size of the Bbaa1 interval, and confirmed the contribution of type I IFN genes to Lyme arthritis. RNA sequencing of resident CD45 - joint cells from advanced interval-specific recombinant congenic lines identified myostatin as uniquely upregulated in association with Bbaa1 arthritis development, and myostatin expression was linked to IFN-β production. Inhibition of myostatin in vivo suppressed Lyme arthritis in the reduced interval Bbaa1 congenic mice, formally implicating myostatin as a novel downstream mediator of the joint-specific inflammatory response to B. burgdorferi . Copyright © 2017 by The American Association of Immunologists, Inc.

  19. Differential temporal control of Foxa.a and Zic-r.b specifies brain versus notochord fate in the ascidian embryo.

    Science.gov (United States)

    Ikeda, Tatsuro; Satou, Yutaka

    2017-01-01

    In embryos of an invertebrate chordate, Ciona intestinalis, two transcription factors, Foxa.a and Zic-r.b, are required for specification of the brain and the notochord, which are derived from distinct cell lineages. In the brain lineage, Foxa.a and Zic-r.b are expressed with no temporal overlap. In the notochord lineage, Foxa.a and Zic-r.b are expressed simultaneously. In the present study, we found that the temporally non-overlapping expression of Foxa.a and Zic-r.b in the brain lineage was regulated by three repressors: Prdm1-r.a (formerly called BZ1), Prdm1-r.b (BZ2) and Hes.a. In morphant embryos of these three repressor genes, Foxa.a expression was not terminated at the normal time, and Zic-r.b was precociously expressed. Consequently, Foxa.a and Zic-r.b were expressed simultaneously, which led to ectopic activation of Brachyury and its downstream pathways for notochord differentiation. Thus, temporal controls by transcriptional repressors are essential for specification of the two distinct fates of brain and notochord by Foxa.a and Zic-r.b Such a mechanism might enable the repeated use of a limited repertoire of transcription factors in developmental gene regulatory networks. © 2017. Published by The Company of Biologists Ltd.

  20. Differential relations of locus of control to perceived social stress among help-seeking adolescents at low vs. high clinical risk of psychosis.

    Science.gov (United States)

    Millman, Zachary B; Weintraub, Marc J; Bentley, Eryn; DeVylder, Jordan E; Mittal, Vijay A; Pitts, Steven C; Thompson, Elizabeth; Demro, Caroline; Reeves, Gloria M; Schiffman, Jason

    2017-06-01

    Research suggests that perceived social stress influences illness presentation and course among youth in the clinical high-risk (CHR) phase of psychosis. Little is known, however, about the social cognitive factors associated with social stress perception in this population, particularly relative to youth with non-CHR psychopathology. Individuals with psychosis tend to endorse an external locus of control (LOC), which is associated with the stress response in healthy individuals. LOC may therefore be related to perceived social stress in youth at CHR. We examined the differential relations of self-reported LOC and perceived social stress, as measured by the Behavior Assessment System for Children, Second Edition, across 45 CHR and 65 help-seeking control (HSC) participants. Youth at CHR reported more social stress (F[1, 107]=6.28, p=0.01) and a more external LOC (F[1, 107]=4.98, p=0.03) than HSCs. Further, external LOC was more strongly associated with feelings of social stress in the CHR group relative to the HSC group (interaction: b=0.35, t[105]=2.32, psocial stress, however, were nonsignificant at internal levels of LOC (b=-2.0, t[105]=-0.72, p=0.48; f 2 =0.00). Results suggest that perceptions of uncontrollability over one's social environment may more often induce or exacerbate feelings of stress and tension in CHR youth relative to HSCs. A better understanding of the social cognition-stress relation may improve understanding of CHR phenomenology, etiology, and treatment. Copyright © 2016 Elsevier B.V. All rights reserved.

  1. Dietary habits during the 2 months following the Chernobyl accident and differentiated thyroid cancer risk in a population-based case-control study.

    Science.gov (United States)

    Xhaard, Constance; Rubino, Carole; Souchard, Vincent; Maillard, Stéphane; Ren, Yan; Borson-Chazot, Françoise; Sassolas, Geneviève; Schvartz, Claire; Colonna, Marc; Lacour, Brigitte; Woronoff, Anne Sophie; Velten, Michel; Marrer, Emilie; Bailly, Laurent; Mariné Barjoan, Eugènia; Schlumberger, Martin; Drozdovitch, Vladimir; Bouville, Andre; Orgiazzi, Jacques; Adjadj, Elisabeth; de Vathaire, Florent

    2018-02-01

    The Chernobyl nuclear power plant accident occurred in Ukraine on April 26th 1986. In France, the radioactive fallout and thyroid radiation doses were much lower than in highly contaminated areas. However, a number of risk projections have suggested that a small excess in differentiated thyroid cancer (DTC) might occur in eastern France due to this low-level fallout. In order to investigate this potential impact, a case-control study on DTC risk factors was started in 2005, focusing on cases who were less than 15 years old at the time of the Chernobyl accident. Here, we aim to evaluate the relationship between some specific reports of potentially contaminated food between April and June 1986 - in particular fresh dairy products and leafy vegetables - and DTC risk. After excluding subjects who were not born before the Chernobyl accident, the study included 747 cases of DTC matched with 815 controls. Odds ratios were calculated using conditional logistic regression models and were reported for all participants, for women only, for papillary cancer only, and excluding microcarcinomas. The DTC risk was slightly higher for participants who had consumed locally produced leafy vegetables. However, this association was not stronger in the more contaminated areas than in the others. Conversely, the reported consumption of fresh dairy products was not statistically associated with DTC risk. Because the increase in DTC risk associated with a higher consumption of locally produced vegetables was not more important in the most contaminated areas, our study lacked power to provide evidence for a strong association between consumption of potentially contaminated food and DTC risk. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Differential discriminator

    International Nuclear Information System (INIS)

    Dukhanov, V.I.; Mazurov, I.B.

    1981-01-01

    A principal flowsheet of a differential discriminator intended for operation in a spectrometric circuit with statistical time distribution of pulses is described. The differential discriminator includes four integrated discriminators and a channel of piled-up signal rejection. The presence of the rejection channel enables the discriminator to operate effectively at loads of 14x10 3 pulse/s. The temperature instability of the discrimination thresholds equals 250 μV/ 0 C. The discrimination level changes within 0.1-5 V, the level shift constitutes 0.5% for the filling ratio of 1:10. The rejection coefficient is not less than 90%. Alpha spectrum of the 228 Th source is presented to evaluate the discriminator operation with the rejector. The rejector provides 50 ns time resolution

  3. Differential topology

    CERN Document Server

    Margalef-Roig, J

    1992-01-01

    ...there are reasons enough to warrant a coherent treatment of the main body of differential topology in the realm of Banach manifolds, which is at the same time correct and complete. This book fills the gap: whenever possible the manifolds treated are Banach manifolds with corners. Corners add to the complications and the authors have carefully fathomed the validity of all main results at corners. Even in finite dimensions some results at corners are more complete and better thought out here than elsewhere in the literature. The proofs are correct and with all details. I see this book as a reliable monograph of a well-defined subject; the possibility to fall back to it adds to the feeling of security when climbing in the more dangerous realms of infinite dimensional differential geometry. Peter W. Michor

  4. Differential belongings

    DEFF Research Database (Denmark)

    Oldrup, Helene

    2014-01-01

    This paper explores suburban middle-class residents’ narratives about housing choice, everyday life and belonging in residential areas of Greater Copenhagen, Denmark, to understand how residential processes of social differentiation are constituted. Using Savage et al.’s concepts of discursive...... and not only to the area itself. In addition, rather than seeing suburban residential areas as homogenous, greater attention should be paid to differences within such areas....

  5. KRAS rs61764370 is associated with HER2-overexpressed and poorly-differentiated breast cancer in hormone replacement therapy users: a case control study

    Directory of Open Access Journals (Sweden)

    Cerne Jasmina-Ziva

    2012-03-01

    Full Text Available Abstract Background A single nucleotide polymorphism located in the 3'-untranslated region of the KRAS oncogene (KRAS variant; rs61764370 disrupts a let-7 miRNA binding and was recently reported to act as a genetic marker for increased risk of developing human cancers. We aimed to investigate an association of the KRAS variant with sporadic and familial breast cancer and breast tumor characteristics. Methods Genotyping was accomplished in 530 sporadic postmenopausal breast cancer cases, 165 familial breast cancer cases (including N = 29, who test positive for BRCA1/2 mutations and 270 postmenopausal control women using the flurogenic 5' nuclease assay. Information on hormone replacement therapy (HRT use and tumor characteristics in sporadic breast cancer cases was ascertained from a postal questionnaire and pathology reports, respectively. Associations between the KRAS genotype and breast cancer or breast tumor characteristics were assessed using chi-square test and logistic regression models. Results No evidence of association was observed between the KRAS variant and risk of sporadic and familial breast cancer - either among BRCA carriers or non-BRCA carriers. The KRAS variant was statistically significantly more often associated with human epidermal growth factor receptor 2 (HER2 - positive tumors and tumors of higher histopathologic grade. However, both associations were detected only in HRT users. Conclusion Our data do not support the hypothesis that the KRAS variant rs61764370 is implicated in the aetiology of sporadic or of familial breast cancer. In postmenopausal women using HRT, the KRAS variant might lead to HER2 overexpressed and poorly-differentiated breast tumors, both indicators of a worse prognosis.

  6. KRAS rs61764370 is associated with HER2-overexpressed and poorly-differentiated breast cancer in hormone replacement therapy users: a case control study

    International Nuclear Information System (INIS)

    Cerne, Jasmina-Ziva; Stegel, Vida; Gersak, Ksenija; Novakovic, Srdjan

    2012-01-01

    A single nucleotide polymorphism located in the 3'-untranslated region of the KRAS oncogene (KRAS variant; rs61764370) disrupts a let-7 miRNA binding and was recently reported to act as a genetic marker for increased risk of developing human cancers. We aimed to investigate an association of the KRAS variant with sporadic and familial breast cancer and breast tumor characteristics. Genotyping was accomplished in 530 sporadic postmenopausal breast cancer cases, 165 familial breast cancer cases (including N = 29, who test positive for BRCA1/2 mutations) and 270 postmenopausal control women using the flurogenic 5' nuclease assay. Information on hormone replacement therapy (HRT) use and tumor characteristics in sporadic breast cancer cases was ascertained from a postal questionnaire and pathology reports, respectively. Associations between the KRAS genotype and breast cancer or breast tumor characteristics were assessed using chi-square test and logistic regression models. No evidence of association was observed between the KRAS variant and risk of sporadic and familial breast cancer - either among BRCA carriers or non-BRCA carriers. The KRAS variant was statistically significantly more often associated with human epidermal growth factor receptor 2 (HER2) - positive tumors and tumors of higher histopathologic grade. However, both associations were detected only in HRT users. Our data do not support the hypothesis that the KRAS variant rs61764370 is implicated in the aetiology of sporadic or of familial breast cancer. In postmenopausal women using HRT, the KRAS variant might lead to HER2 overexpressed and poorly-differentiated breast tumors, both indicators of a worse prognosis

  7. Differential geometry

    CERN Document Server

    Ciarlet, Philippe G

    2007-01-01

    This book gives the basic notions of differential geometry, such as the metric tensor, the Riemann curvature tensor, the fundamental forms of a surface, covariant derivatives, and the fundamental theorem of surface theory in a selfcontained and accessible manner. Although the field is often considered a classical one, it has recently been rejuvenated, thanks to the manifold applications where it plays an essential role. The book presents some important applications to shells, such as the theory of linearly and nonlinearly elastic shells, the implementation of numerical methods for shells, and

  8. Differential equations

    CERN Document Server

    Tricomi, FG

    2013-01-01

    Based on his extensive experience as an educator, F. G. Tricomi wrote this practical and concise teaching text to offer a clear idea of the problems and methods of the theory of differential equations. The treatment is geared toward advanced undergraduates and graduate students and addresses only questions that can be resolved with rigor and simplicity.Starting with a consideration of the existence and uniqueness theorem, the text advances to the behavior of the characteristics of a first-order equation, boundary problems for second-order linear equations, asymptotic methods, and diff

  9. Differential topology

    CERN Document Server

    Guillemin, Victor

    2010-01-01

    Differential Topology provides an elementary and intuitive introduction to the study of smooth manifolds. In the years since its first publication, Guillemin and Pollack's book has become a standard text on the subject. It is a jewel of mathematical exposition, judiciously picking exactly the right mixture of detail and generality to display the richness within. The text is mostly self-contained, requiring only undergraduate analysis and linear algebra. By relying on a unifying idea-transversality-the authors are able to avoid the use of big machinery or ad hoc techniques to establish the main

  10. Effect of fO2 on phase relationship in basaltic andesites during magmatic differentiation: Control of fO2 and sulphur speciation in piston cylinder experiments.

    Science.gov (United States)

    Matjuschkin, Vladimir; Tattitch, Brian; Blundy, Jonathan D.; Skora, Susanne

    2014-05-01

    Within the mantle wedge above subduction zones, oxidation reaction take place by interaction of reduced mantle rocks with more oxidized, hydrous fluids, which can cause a local drop of the solidus, resulting in partial melting (2,6,7). The resultant melts are more oxidized that their ocean floor counterparts, which has implications for their subsequent differentiation paths, the speciation of multivalent elements and the solubility and transport of chemical compounds in magmatic systems (1,4,5). We present a series of sulphur-doped high-pressure experiments conducted to investigate the effect of oxygen fugacity on phase relationships and the behaviour of sulphur in silicate melts. Natural aphyric andesite (FM37) erupted from Laguna del Maule volcano, Chile (3) was selected as a starting composition. Experiments were carried out at 5kbar, 950-1150° C and variable oxygen fugacity conditions. New experiments buffered at Co-CoO and Ni-NiO buffer conditions have been performed using a new "MTB capsule design" developed in order to accurately control fO2 by means of a double capsule containing metal-oxide buffers and a pyrex sleeve to minimise H2 diffusion. This new design constrains oxygen fugacity to within ±0.1-0.2logfO2 units of the target value. Before conducting these experiments, the assemblage was tested multiple times at 10kbar, 1000° C over 24-48 hours and demonstrated consistent, accurate fO2 control. Analyses of the preliminary experimental run products, from a related Chilean basaltic andesite starting composition, demonstrate a clear effect of fO2 on phase relationships and the proportion of melt generated during experiments. Under oxidized conditions, as temperature decreased from 1150° C to 1050° C, the amount of melt decreased from 100% to ~80%, due to the formation of orthopyroxene, anhydrite and plagioclase. In contrast, in reduced runs the system remains nearly liquid (~5% crystals) down to 950° C due to the change in sulphur speciation and

  11. Neisseria meningitidis differentially controls host cell motility through PilC1 and PilC2 components of type IV Pili.

    Directory of Open Access Journals (Sweden)

    Philippe C Morand

    Full Text Available Neisseria meningitidis is a strictly human pathogen that has two facets since asymptomatic carriage can unpredictably turn into fulminant forms of infection. Meningococcal pathogenesis relies on the ability of the bacteria to break host epithelial or endothelial cellular barriers. Highly restrictive, yet poorly understood, mechanisms allow meningococcal adhesion to cells of only human origin. Adhesion of encapsulated and virulent meningococci to human cells relies on the expression of bacterial type four pili (T4P that trigger intense host cell signalling. Among the components of the meningococcal T4P, the concomitantly expressed PilC1 and PilC2 proteins regulate pili exposure at the bacterial surface, and until now, PilC1 was believed to be specifically responsible for T4P-mediated meningococcal adhesion to human cells. Contrary to previous reports, we show that, like PilC1, the meningococcal PilC2 component is capable of mediating adhesion to human ME180 epithelial cells, with cortical plaque formation and F-actin condensation. However, PilC1 and PilC2 promote different effects on infected cells. Cellular tracking analysis revealed that PilC1-expressing meningococci caused a severe reduction in the motility of infected cells, which was not the case when cells were infected with PilC2-expressing strains. The amount of both total and phosphorylated forms of EGFR was dramatically reduced in cells upon PilC1-mediated infection. In contrast, PilC2-mediated infection did not notably affect the EGFR pathway, and these specificities were shared among unrelated meningococcal strains. These results suggest that meningococci have evolved a highly discriminative tool for differential adhesion in specific microenvironments where different cell types are present. Moreover, the fine-tuning of cellular control through the combined action of two concomitantly expressed, but distinctly regulated, T4P-associated variants of the same molecule (i.e. PilC1 and Pil

  12. Effects of hanging drop culture conditions on embryoid body formation and neuronal cell differentiation using mouse embryonic stem cells: optimization of culture conditions for the formation of well-controlled embryoid bodies.

    Science.gov (United States)

    Ohnuki, Yoshitsugu; Kurosawa, Hiroshi

    2013-05-01

    Hanging drop (HD) cultures were carried out with a drop volume of either 20 or 30 μl. An incubation period of 3 days was determined to be appropriate for the formation of well-controlled embryoid bodies (EBs), and the initial cell number was identified as the most critical factor in the growth and neuronal cell differentiation of EBs. Copyright © 2012 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  13. On matrix fractional differential equations

    Directory of Open Access Journals (Sweden)

    Adem Kılıçman

    2017-01-01

    Full Text Available The aim of this article is to study the matrix fractional differential equations and to find the exact solution for system of matrix fractional differential equations in terms of Riemann–Liouville using Laplace transform method and convolution product to the Riemann–Liouville fractional of matrices. Also, we show the theorem of non-homogeneous matrix fractional partial differential equation with some illustrative examples to demonstrate the effectiveness of the new methodology. The main objective of this article is to discuss the Laplace transform method based on operational matrices of fractional derivatives for solving several kinds of linear fractional differential equations. Moreover, we present the operational matrices of fractional derivatives with Laplace transform in many applications of various engineering systems as control system. We present the analytical technique for solving fractional-order, multi-term fractional differential equation. In other words, we propose an efficient algorithm for solving fractional matrix equation.

  14. Differential Internalization Rates and Postendocytic Sorting of the Norepinephrine and Dopamine Transporters Are Controlled by Structural Elements in the N Termini

    DEFF Research Database (Denmark)

    Vuorenpää, Anne Elina; Jørgensen, Trine Nygaard; Newman, Amy H

    2016-01-01

    . Moreover, mitigating Rab11 function by overexpression of dominant negative Rab11 impaired NET function. Sorting of NET to the Rab11 recycling compartment was further supported by confocal imaging and reversible biotinylation experiments in transfected differentiated CATH.a cells. In contrast to NET......, the dopamine transporter displayed markedly less constitutive internalization and limited sorting to the Rab11 recycling compartment in the differentiated CATH.a cells. Exchange of domains between the two homologous transporters revealed that this difference was determined by non-conserved structural elements...... in the intracellular N terminus. We conclude that NET displays a distinct trafficking itinerary characterized by continuous shuffling between the plasma membrane and the Rab11 recycling compartment and that the functional integrity of the Rab11 compartment is critical for maintaining proper presynaptic NET function....

  15. Synergistic efficacy of a novel combination therapy controls growth of Bcl-x(L) bountiful neuroblastoma cells by increasing differentiation and apoptosis.

    Science.gov (United States)

    Mohan, Nishant; Banik, Naren L; Ray, Swapan K

    2011-11-01

    Neuroblastoma is the most prevalent extracranial solid tumor mainly in pediatric patients. We explored the efficacy of the combination of 2[(3-[2,3-dichlorophenoxy]propyl)amino]ethanol (2,3-DCPE, a small molecule inhibitor of the anti-apoptotic protein Bcl-x(L)) and N-(4-hydroxyphenyl) retinamide (4-HPR, a synthetic retinoid) in inducing differentiation and apoptosis in human malignant neuroblastoma cells. Immunofluorescence confocal microscopy and flow cytometry showed that the highest level of Bcl-x(L) expression occurred in SK-N-DZ cells followed by SH-SY5Y and IMR-32 cells. Combination of 20 μM 2,3-DCPE and 1 μM 4-HPR acted synergistically in decreasing viability of SK-N-DZ and SH-SY5Y cells. In situ methylene blue staining and protein gel blotting showed the efficacy of this combination of drugs in inducing neuronal differentiation morphologically and also biochemically with upregulation of the neuronal markers such as neurofilament protein (NFP) and neuron specific enolase (NSE) and downregulation of the differentiation inhibiting molecules such as N-Myc and Notch-1 in SK-N-DZ and SH-SY5Y cells. Annexin V-FITC/PI staining showed the synergistic action of this combination therapy in increasing apoptosis in both cell lines. Protein gel blotting manifested that combination therapy increased apoptosis with downregulation of the anti-apoptotic proteins Bcl-x(L), Bcl-2 and Mcl-1 and upregulation of the pro-apoptotic proteins Bax, p53, Puma (p53 upregulated modulator of apoptosis), and Noxa, ultimately causing activation of caspase-3. In conclusion, our results appeared highly encouraging in advocating the use of 2,3-DCPE and 4-HPR as a novel combination therapy for increasing both differentiation and apoptosis in human malignant neuroblastoma cells having Bcl-x(L) overexpression.

  16. The diameter of nanotubes formed on Ti-6Al-4V alloy controls the adhesion and differentiation of Saos-2 cells

    Czech Academy of Sciences Publication Activity Database

    Filová, Elena; Fojt, J.; Krýslová, Markéta; Moravec, H.; Joska, L.; Bačáková, Lucie

    2015-01-01

    Roč. 10, 20 Nov (2015), s. 7145-7163 E-ISSN 1178-2013 R&D Projects: GA MZd(CZ) NT13297; GA ČR(CZ) GA15-01558S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:67985823 Keywords : nanostructure * titanium nanotubes * cell adhesion * Saos-2 cells * osteogenic differentiation Subject RIV: EI - Biotechnology ; Bionics Impact factor: 4.320, year: 2015

  17. PaASK1, a mitogen-activated protein kinase kinase kinase that controls cell degeneration and cell differentiation in Podospora anserina.

    Science.gov (United States)

    Kicka, Sébastien; Silar, Philippe

    2004-03-01

    MAPKKK are kinases involved in cell signaling. In fungi, these kinases are known to regulate development, pathogenicity, and the sensing of external conditions. We show here that Podospora anserina strains mutated in PaASK1, a MAPKKK of the MEK family, are impaired in the development of crippled growth, a cell degeneration process caused by C, a nonconventional infectious element. They also display defects in mycelium pigmentation, differentiation of aerial hyphae, and making of fruiting bodies, three hallmarks of cell differentiation during stationary phase in P. anserina. Overexpression of PaASK1 results in exacerbation of crippled growth. PaASK1 is a large protein of 1832 amino acids with several domains, including a region rich in proline and a 60-amino-acid-long polyglutamine stretch. Deletion analysis reveals that the polyglutamine stretch is dispensable for PaASK1 activity, whereas the region that contains the prolines is essential but insufficient to promote full activity. We discuss a model based on the hysteresis of a signal transduction cascade to account for the role of PaASK1 in both cell degeneration and stationary-phase cell differentiation.

  18. Investigation of Laser Induced Breakdown Spectroscopy (LIBS) for the Differentiation of Nerve and Gland Tissue—A Possible Application for a Laser Surgery Feedback Control Mechanism

    Science.gov (United States)

    Mehari, F.; Rohde, M.; Knipfer, C.; Kanawade, R.; Klämpfl, F.; W., Adler; Oetter, N.; Stelzle, F.; Schmidt, M.

    2016-06-01

    Laser surgery provides clean, fast and accurate modeling of tissue. However, the inability to determine what kind of tissue is being ablated at the bottom of the cut may lead to the iatrogenic damage of structures that were meant to be preserved. In this context, nerve preservation is one of the key challenges in any surgical procedure. One example is the treatment of parotid gland pathologies, where the facial nerve (N. VII) and its main branches run through and fan out inside the glands parenchyma. A feedback system that automatically stops the ablation to prevent nerve-tissue damage could greatly increase the applicability and safety of surgical laser systems. In the present study, Laser Induced Breakdown Spectroscopy (LIBS) is used to differentiate between nerve and gland tissue of an ex-vivo pig animal model. The LIBS results obtained in this preliminary experiment suggest that the measured spectra, containing atomic and molecular emissions, can be used to differentiate between the two tissue types. The measurements and differentiation were performed in open air and under normal stray light conditions.

  19. Differential geometric methods in system theory.

    Science.gov (United States)

    Brockett, R. W.

    1971-01-01

    Discussion of certain problems in system theory which have been or might be solved using some basic concepts from differential geometry. The problems considered involve differential equations, controllability, optimal control, qualitative behavior, stochastic processes, and bilinear systems. The main goal is to extend the essentials of linear theory to some nonlinear classes of problems.

  20. New Methodology for Optimal Flight Control Using Differential Evolution Algorithms Applied on the Cessna Citation X Business Aircraft – Part 1. Design and Optimization

    OpenAIRE

    Yamina BOUGHARI; Georges GHAZI; Ruxandra Mihaela BOTEZ; Florian THEEL

    2017-01-01

    Setting the appropriate controllers for aircraft stability and control augmentation systems are complicated and time consuming tasks. As in the Linear Quadratic Regulator method gains are found by selecting the appropriate weights or as in the Proportional Integrator Derivative control by tuning gains. A trial and error process is usually employed for the determination of weighting matrices, which is normally a time consuming procedure. Flight Control Law were optimized and designed by combin...

  1. Centriole, differentiation, and senescence.

    Science.gov (United States)

    Tkemaladze, J; Chichinadze, K

    2010-01-01

    Irreversible differentiation (change of morphogenetic status) and programmed death (apoptosis) are observed only in somatic cells, and cell division is the only way by which the morphogenetic status of the offspring cells may be modified. It is known that there is a fixed limit to the number of possible cell divisions, the so-called Hayflick limit. Existing links between cell division, differentiation, and apoptosis make it possible to conclude that all of these processes could be controlled by a single self-reproducing structure. Potential candidates for this replicable structure in a somatic cell are the chromosomes, mitochondria (both contain DNA), and centrioles. Centrioles (a diplosome, or pair of centrioles) are the most likely unit that can fully regulate the processes of irreversible differentiation, determination, and modification of the morphogenetic status. Centrioles may contain differently encoded RNA molecules stacked in a definite order, and during mitosis, these RNA molecules are released one by one into the cytoplasm. In the presence of reverse transcriptase and endonuclease, processing of this RNA presumably changes the status of repressed and potentially active genes and, subsequently, the morphogenetic status of a cell.

  2. Concentrated Differential Privacy

    OpenAIRE

    Dwork, Cynthia; Rothblum, Guy N.

    2016-01-01

    We introduce Concentrated Differential Privacy, a relaxation of Differential Privacy enjoying better accuracy than both pure differential privacy and its popular "(epsilon,delta)" relaxation without compromising on cumulative privacy loss over multiple computations.

  3. Determination of the most appropriate method for extrapolating overall survival data from a placebo-controlled clinical trial of lenvatinib for progressive, radioiodine-refractory differentiated thyroid cancer

    Directory of Open Access Journals (Sweden)

    Tremblay G

    2016-06-01

    Full Text Available Gabriel Tremblay,1 Christopher Livings,2 Lydia Crowe,2 Venediktos Kapetanakis,2 Andrew Briggs3 1Global Health Economics and Health Technology Assessment, Eisai Inc., Woodcliff Lake, NJ, USA; 2Health Economics, Decision Resources Group, Bicester, Oxfordshire, 3Health Economics and Health Technology Assessment, Institute of Health and Wellbeing, University of Glasgow, Glasgow, UK Background: Cost-effectiveness models for the treatment of long-term conditions often require information on survival beyond the period of available data. Objectives: This paper aims to identify a robust and reliable method for the extrapolation of overall survival (OS in patients with radioiodine-refractory differentiated thyroid cancer receiving lenvatinib or placebo. Methods: Data from 392 patients (lenvatinib: 261, placebo: 131 from the SELECT trial are used over a 34-month period of follow-up. A previously published criterion-based approach is employed to ascertain credible estimates of OS beyond the trial data. Parametric models with and without a treatment covariate and piecewise models are used to extrapolate OS, and a holistic approach, where a series of statistical and visual tests are considered collectively, is taken in determining the most appropriate extrapolation model. Results: A piecewise model, in which the Kaplan–Meier survivor function is used over the trial period and an extrapolated tail is based on the Exponential distribution, is identified as the optimal model. Conclusion: In the absence of long-term survival estimates from clinical trials, survival estimates often need to be extrapolated from the available data. The use of a systematic method based on a priori determined selection criteria provides a transparent approach and reduces the risk of bias. The extrapolated OS estimates will be used to investigate the potential long-term benefits of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer patients and

  4. Take control of upgrading to Snow Leopard

    CERN Document Server

    Kissell, Joe

    2009-01-01

    Installing a major new version of Mac OS X should be exciting and fun, but without proper guidance you may find it nerve-wracking or even risk losing valuable files. Fortunately, many thousands of people have upgraded Mac OS X calmly and successfully with Joe Kissell's previous best-selling Take Control of Upgrading... titles. Joe's friendly, expert steps-developed over innumerable test installations-help you to avoid trouble, understand what's going on when you install Snow Leopard, and easily recover from problem

  5. Determination of the most appropriate method for extrapolating overall survival data from a placebo-controlled clinical trial of lenvatinib for progressive, radioiodine-refractory differentiated thyroid cancer.

    Science.gov (United States)

    Tremblay, Gabriel; Livings, Christopher; Crowe, Lydia; Kapetanakis, Venediktos; Briggs, Andrew

    2016-01-01

    Cost-effectiveness models for the treatment of long-term conditions often require information on survival beyond the period of available data. This paper aims to identify a robust and reliable method for the extrapolation of overall survival (OS) in patients with radioiodine-refractory differentiated thyroid cancer receiving lenvatinib or placebo. Data from 392 patients (lenvatinib: 261, placebo: 131) from the SELECT trial are used over a 34-month period of follow-up. A previously published criterion-based approach is employed to ascertain credible estimates of OS beyond the trial data. Parametric models with and without a treatment covariate and piecewise models are used to extrapolate OS, and a holistic approach, where a series of statistical and visual tests are considered collectively, is taken in determining the most appropriate extrapolation model. A piecewise model, in which the Kaplan-Meier survivor function is used over the trial period and an extrapolated tail is based on the Exponential distribution, is identified as the optimal model. In the absence of long-term survival estimates from clinical trials, survival estimates often need to be extrapolated from the available data. The use of a systematic method based on a priori determined selection criteria provides a transparent approach and reduces the risk of bias. The extrapolated OS estimates will be used to investigate the potential long-term benefits of lenvatinib in the treatment of radioiodine-refractory differentiated thyroid cancer patients and populate future cost-effectiveness analyses.

  6. New Methodology for Optimal Flight Control Using Differential Evolution Algorithms Applied on the Cessna Citation X Business Aircraft – Part 1. Design and Optimization

    Directory of Open Access Journals (Sweden)

    Yamina BOUGHARI

    2017-06-01

    Full Text Available Setting the appropriate controllers for aircraft stability and control augmentation systems are complicated and time consuming tasks. As in the Linear Quadratic Regulator method gains are found by selecting the appropriate weights or as in the Proportional Integrator Derivative control by tuning gains. A trial and error process is usually employed for the determination of weighting matrices, which is normally a time consuming procedure. Flight Control Law were optimized and designed by combining the Deferential Evolution algorithm, the Linear Quadratic Regulator method, and the Proportional Integral controller. The optimal controllers were used to reach satisfactory aircraft’s dynamic and safe flight operations with respect to the augmentation systems’ handling qualities, and design requirements for different flight conditions. Furthermore the design and the clearance of the controllers over the flight envelope were automated using a Graphical User Interface, which offers to the designer, the flexibility to change the design requirements. In the aim of reducing time, and costs of the Flight Control Law design, one fitness function has been used for both optimizations, and using design requirements as constraints. Consequently the Flight Control Law design process complexity was reduced by using the meta-heuristic algorithm.

  7. Relating specific emotions to intrinsic motivation: on the moderating role of positive and negative emotion differentiation.

    Science.gov (United States)

    Vandercammen, Leen; Hofmans, Joeri; Theuns, Peter

    2014-01-01

    Despite the fact that studies on self-determination theory have traditionally disregarded the explicit role of emotions in the motivation eliciting process, research attention for the affective antecedents of motivation is growing. We add to this emerging research field by testing the moderating role of emotion differentiation -individual differences in the extent to which people can differentiate between specific emotions- on the relationship between twelve specific emotions and intrinsic motivation. To this end, we conducted a daily diary study (N = 72) and an experience sampling study (N = 34). Results showed that the relationship between enthusiasm, cheerfulness, optimism, contentedness, gloominess, miserableness, uneasiness (in both studies 1 and 2), calmness, relaxation, tenseness, depression, worry (only in Study 1) on one hand and intrinsic motivation on the other hand was moderated by positive emotion differentiation for the positive emotions and by negative emotion differentiation for the negative emotions. Altogether, these findings suggest that for people who are unable to distinguish between different specific positive emotions the relationship between those specific positive emotions and intrinsic motivation is stronger, whereas the relationship between specific negative emotions and intrinsic motivation is weaker for people who are able to distinguish between the different specific negative emotions. Theoretical and practical implications are discussed.

  8. Relating Specific Emotions to Intrinsic Motivation: On the Moderating Role of Positive and Negative Emotion Differentiation

    Science.gov (United States)

    Vandercammen, Leen; Hofmans, Joeri; Theuns, Peter

    2014-01-01

    Despite the fact that studies on self-determination theory have traditionally disregarded the explicit role of emotions in the motivation eliciting process, research attention for the affective antecedents of motivation is growing. We add to this emerging research field by testing the moderating role of emotion differentiation –individual differences in the extent to which people can differentiate between specific emotions– on the relationship between twelve specific emotions and intrinsic motivation. To this end, we conducted a daily diary study (N = 72) and an experience sampling study (N = 34). Results showed that the relationship between enthusiasm, cheerfulness, optimism, contentedness, gloominess, miserableness, uneasiness (in both studies 1 and 2), calmness, relaxation, tenseness, depression, worry (only in Study 1) on one hand and intrinsic motivation on the other hand was moderated by positive emotion differentiation for the positive emotions and by negative emotion differentiation for the negative emotions. Altogether, these findings suggest that for people who are unable to distinguish between different specific positive emotions the relationship between those specific positive emotions and intrinsic motivation is stronger, whereas the relationship between specific negative emotions and intrinsic motivation is weaker for people who are able to distinguish between the different specific negative emotions. Theoretical and practical implications are discussed. PMID:25517984

  9. Relating specific emotions to intrinsic motivation: on the moderating role of positive and negative emotion differentiation.

    Directory of Open Access Journals (Sweden)

    Leen Vandercammen

    Full Text Available Despite the fact that studies on self-determination theory have traditionally disregarded the explicit role of emotions in the motivation eliciting process, research attention for the affective antecedents of motivation is growing. We add to this emerging research field by testing the moderating role of emotion differentiation -individual differences in the extent to which people can differentiate between specific emotions- on the relationship between twelve specific emotions and intrinsic motivation. To this end, we conducted a daily diary study (N = 72 and an experience sampling study (N = 34. Results showed that the relationship between enthusiasm, cheerfulness, optimism, contentedness, gloominess, miserableness, uneasiness (in both studies 1 and 2, calmness, relaxation, tenseness, depression, worry (only in Study 1 on one hand and intrinsic motivation on the other hand was moderated by positive emotion differentiation for the positive emotions and by negative emotion differentiation for the negative emotions. Altogether, these findings suggest that for people who are unable to distinguish between different specific positive emotions the relationship between those specific positive emotions and intrinsic motivation is stronger, whereas the relationship between specific negative emotions and intrinsic motivation is weaker for people who are able to distinguish between the different specific negative emotions. Theoretical and practical implications are discussed.

  10. Differential Internalization Rates and Postendocytic Sorting of the Norepinephrine and Dopamine Transporters Are Controlled by Structural Elements in the N Termini*

    Science.gov (United States)

    Vuorenpää, Anne; Jørgensen, Trine N.; Newman, Amy H.; Madsen, Kenneth L.; Scheinin, Mika

    2016-01-01

    The norepinephrine transporter (NET) mediates reuptake of synaptically released norepinephrine in central and peripheral noradrenergic neurons. The molecular processes governing availability of NET in the plasma membrane are poorly understood. Here we use the fluorescent cocaine analogue JHC 1-64, as well as several other approaches, to investigate the trafficking itinerary of NET in live noradrenergic neurons. Confocal imaging revealed extensive constitutive internalization of JHC 1-64-labeled NET in the neuronal somata, proximal extensions and presynaptic boutons. Phorbol 12-myristate 13-acetate increased intracellular accumulation of JHC 1-64-labeled NET and caused a parallel reduction in uptake capacity. Internalized NET strongly colocalized with the “long loop” recycling marker Rab11, whereas less overlap was seen with the “short loop” recycling marker Rab4 and the late endosomal marker Rab7. Moreover, mitigating Rab11 function by overexpression of dominant negative Rab11 impaired NET function. Sorting of NET to the Rab11 recycling compartment was further supported by confocal imaging and reversible biotinylation experiments in transfected differentiated CATH.a cells. In contrast to NET, the dopamine transporter displayed markedly less constitutive internalization and limited sorting to the Rab11 recycling compartment in the differentiated CATH.a cells. Exchange of domains between the two homologous transporters revealed that this difference was determined by non-conserved structural elements in the intracellular N terminus. We conclude that NET displays a distinct trafficking itinerary characterized by continuous shuffling between the plasma membrane and the Rab11 recycling compartment and that the functional integrity of the Rab11 compartment is critical for maintaining proper presynaptic NET function. PMID:26786096

  11. Differential rate in decline in ovarian reserve markers in women with polycystic ovary syndrome compared with control subjects: results of a longitudinal study.

    Science.gov (United States)

    Ahmad, Asima K; Kao, Chia-Ning; Quinn, Molly; Lenhart, Nikolaus; Rosen, Mitchell; Cedars, Marcelle I; Huddleston, Heather

    2018-03-01

    To estimate rates of ovarian aging in polycystic ovary syndrome (PCOS) subjects versus a community control population. Longitudinal. Tertiary academic center. PCOS subjects diagnosed according to the 2004 Rotterdam criteria were systematically enrolled in a PCOS cohort study. The comparison control subjects were from the Ovarian Aging study, a prospective longitudinal study of ovarian aging in healthy women with regular menstrual cycles. Clinical data collection over two study visits. Antral follicle count (AFC), ovarian volume (OV), and antimüllerian hormone level (AMH). PCOS subjects were found to have higher baseline values for all ovarian reserve markers compared with control subjects. Univariate models indicated that, compared with control subjects, PCOS patients experienced significantly faster rates of decline for both AFC and AMH. Change in OV did not differ significantly. To account for potential confounder effects, multiple analysis of covariance models were evaluated for the best fit, considering age, body mass index, and baseline ovarian reserve markers. Adjusted models demonstrated that PCOS patients do not experience a significant difference in AFC decline compared with control subjects, but they do experience a faster rate of decline in AMH (POvarian aging in PCOS is characterized by a more rapid decline in AMH and a slower decline in OV compared with control subjects. Copyright © 2017 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  12. Randomized controlled trial for Salvia sclarea or Lavandula angustifolia: differential effects on blood pressure in female patients with urinary incontinence undergoing urodynamic examination.

    Science.gov (United States)

    Seol, Geun Hee; Lee, Yun Hee; Kang, Purum; You, Ji Hye; Park, Mira; Min, Sun Seek

    2013-07-01

    The aim of this study was to investigate the effect of inhalation of Salvia sclarea (clary sage; clary) or Lavandula angustifolia (lavender) essential oil vapors on autonomic nervous system activity in female patients with urinary incontinence undergoing urodynamic assessment. STUDY DESIGN, LOCATION, AND SUBJECTS: This study was a double-blind, randomized, controlled trial carried out in 34 female patients with urinary incontinence. The subjects were randomized to inhale lavender, clary, or almond (control) oil at concentrations of 5% (vol/vol) each. Systolic blood pressure, diastolic blood pressure, pulse rate, respiratory rate, and salivary cortisol were measured before and after inhalation of these odors for 60 minutes. The clary oil group experienced a significant decrease in systolic blood pressure compared with the control (p=0.048) and lavender oil (p=0.026) groups, a significant decrease in diastolic blood pressure compared with the lavender oil group (p=0.034) and a significant decrease in respiratory rate compared with the control group (p<0.001). In contrast, the lavender oil group tended to increase systolic and diastolic blood pressure compared with the control group. Compared with the control group, inhalation of lavender oil (p=0.045) and clary oil (p<0.001) resulted in statistically significant reductions in respiratory rate. These results suggest that lavender oil inhalation may be inappropriate in lowering stress during urodynamic examinations, despite its antistress effects, while clary oil inhalation may be useful in inducing relaxation in female urinary incontinence patients undergoing urodynamic assessments.

  13. Impulsive differential inclusions a fixed point approach

    CERN Document Server

    Ouahab, Abdelghani; Henderson, Johnny

    2013-01-01

    Impulsive differential equations have been developed in modeling impulsive problems in physics, population dynamics, ecology, biotechnology, industrial robotics, pharmacokinetics, optimal control, etc. The questions of existence and stability of solutions for different classes of initial values problems for impulsive differential equations and inclusions with fixed and variable moments are considered in detail. Attention is also given to boundary value problems and relative questions concerning differential equations. This monograph addresses a variety of side issues that arise from its simple

  14. Differential effects of decision latitude and control on the job demands-strain relationship: a cross-sectional survey study among elderly care nursing staff.

    Science.gov (United States)

    Schmidt, Klaus-Helmut; Diestel, Stefan

    2011-03-01

    According to the influential Job Demands-Control (JD-C) model developed by Karasek (1979; Karasek and Theorell, 1990), job strain is expected to result from high job demands and low job control as well as an interaction between both job characteristics. Previous research, however, has found such an interaction only rarely or inconsistently.It has been suggested that the conceptualization of the control variable (formerly referred to as decision latitude) may be particularly responsible for the lack of supportive findings. The present study aimed at clarifying this issue by contrasting a focused measure of control with a traditional measure of decision latitude in their relations to job strain of health care workers. The measure of decision latitude encompassed a wide range of job characteristics including control, task variety, and learning opportunities. A cross-sectional questionnaire survey was conducted with job satisfaction, psychosomatic complaints and emotional exhaustion as criterion measures of job strain. A supra-regional organization for residential elderly care with 11 nursing homes located in a federal state in Germany. Questionnaires were distributed to the whole nursing staff, of which 379 filled in the questionnaire during normal working hours (68% participation rate). In addition to confirmatory factor analyses, descriptive statistics, and bivariate correlations, hierarchical multiple regression analyses were performed for testing the corresponding interaction effects. Findings confirmed the assumption that the focused measure of control and the traditional measure of decision latitude represent distinct, yet correlated factors. Furthermore, findings revealed a significant interaction effect between job demands and control on all outcomes considered. By way of contrast, there was no equivalent interaction effect between job demands and decision latitude. In line with the JD-C model, the adverse influence of increasing demands on job satisfaction

  15. EGFR-TK inhibition before radiotherapy reduces tumour volume but does not improve local control: Differential response of cancer stem cells and nontumourigenic cells?

    International Nuclear Information System (INIS)

    Krause, Mechthild; Prager, Jenny; Zhou Xuanjing; Yaromina, Ala; Doerfler, Annegret; Eicheler, Wolfgang; Baumann, Michael

    2007-01-01

    Background and purpose: Waiting times before radiotherapy may reduce tumour control probability due to proliferation of tumour cells. The aim of the experiment was to test whether the growth inhibiting effect of epidermal growth factor receptor (EGFR)-inhibitors after surgery or tumour transplantation results in a lower tumour mass at time of irradiation and can thereby improve local tumour control. Materials and methods: The EGFR-tyrosine kinase inhibitor BIBX1382BS was applied over 14 days starting from microscopically non-in-sano-resection of FaDu tumours or from tumour transplantation, followed by irradiation (5f/5d). Endpoint was local tumour control. In addition, vital tumour areas, pimonidazole hypoxic fraction, BrdU labelling index, and colony forming ability in vitro were tested in control tumours and after BIBX1382BS treatment (starting from transplantation). Results: The tumour volume at start of irradiation was significantly lower in the BIBX1382BS treated tumours as compared to the control groups by factors of 11 (post-surgery setting) and 2.7 (transplantation setting). However, the reduced volume did not translate into improved local control after irradiation. The TCD 50 values after surgery were 25.4 Gy [95% CI 18; 33 Gy] in the control group and 30.5 Gy [24; 37] in the BIBX1382BS group (p = 0.25). Treatment after transplantation resulted in TCD 50 values of 41.1 Gy [35; 47] in the control group and 41.1 Gy [33; 49] in the BIBX1382BS group (p = 1). While the proportion of S-phase cells decreased after BIBX1382BS treatment, no differences were observed between the pimonidazole hypoxic fractions and in vitro colony forming ability. Conclusions: EGFR-TK inhibition with BIBX1382BS over 14 days between macroscopically complete tumour resection or tumour transplantation and start of radiotherapy significantly reduced tumour volume but did not improve local tumour control. One possible explanation is that the EGFR-TK inhibitor has a higher activity in

  16. Differential effects of rhythmic auditory stimulation and neurodevelopmental treatment/Bobath on gait patterns in adults with cerebral palsy: a randomized controlled trial.

    Science.gov (United States)

    Kim, Soo Ji; Kwak, Eunmi E; Park, Eun Sook; Cho, Sung-Rae

    2012-10-01

    To investigate the effects of rhythmic auditory stimulation (RAS) on gait patterns in comparison with changes after neurodevelopmental treatment (NDT/Bobath) in adults with cerebral palsy. A repeated-measures analysis between the pretreatment and posttreatment tests and a comparison study between groups. Human gait analysis laboratory. Twenty-eight cerebral palsy patients with bilateral spasticity participated in this study. The subjects were randomly allocated to either neurodevelopmental treatment (n = 13) or rhythmic auditory stimulation (n = 15). Gait training with rhythmic auditory stimulation or neurodevelopmental treatment was performed three sessions per week for three weeks. Temporal and kinematic data were analysed before and after the intervention. Rhythmic auditory stimulation was provided using a combination of a metronome beat set to the individual's cadence and rhythmic cueing from a live keyboard, while neurodevelopmental treatment was implemented following the traditional method. Temporal data, kinematic parameters and gait deviation index as a measure of overall gait pathology were assessed. Temporal gait measures revealed that rhythmic auditory stimulation significantly increased cadence, walking velocity, stride length, and step length (P rhythmic auditory stimulation (P rhythmic auditory stimulation (P rhythmic auditory stimulation showed aggravated maximal internal rotation in the transverse plane (P rhythmic auditory stimulation or neurodevelopmental treatment elicited differential effects on gait patterns in adults with cerebral palsy.

  17. Inclusive differentiated instruction

    Directory of Open Access Journals (Sweden)

    Jerković Ljiljana S.

    2017-01-01

    Full Text Available Inclusive differentiated instruction is a new model of didactic instruction, theoretically described and established in this paper for the first time, after being experimentally verified through teaching of the mother tongue (instruction in reading and literature. Inclusive individually planned instruction is based on a phenomenological and constructivist didactic instructional paradigm. This type of teaching is essentially developmental and person-oriented. The key stages of inclusive differentiated instruction of literature are: 1 recognition of individual students' potential and educational needs regarding reading and work on literary texts; 2 planning and preparation of inclusive individually planned instruction in reading and literature; 3 actual class teaching of lessons thus prepared; and 4 evaluation of the student achievement following inclusive differentiated instruction in reading and literature. A highly important element of the planning and preparation of inclusive differentiated instruction is the creation of student profiles and inclusive individualized syllabi. Individualized syllabi specify the following: 1. a brief student profile; 2. the student position on the continuum of the learning outcomes of instruction in the Serbian language; 3. reverse-engineered macro-plan stages of instruction in the Serbian language (3.1. identifying expected outcomes and fundamental qualities of learners' work, 3.2. defining acceptable proofs of their realisation, 3.3. planning learning and teaching experiences, and 3.4. providing material and technical requisites for teaching; 4 the contents and procedure of individualized lessons targeting the student; 5 a plan of syllabus implementation monitoring and evaluation. The continuum of the learning outcomes of inclusive differentiated instruction in literature exists at three main levels, A, B and C. The three levels are: A reading techniques and learning about the main literary theory concepts; B

  18. The RNA binding protein HuR differentially regulates unique subsets of mRNAs in estrogen receptor negative and estrogen receptor positive breast cancer

    Directory of Open Access Journals (Sweden)

    Chen Jing

    2010-04-01

    Full Text Available Abstract Background The discordance between steady-state levels of mRNAs and protein has been attributed to posttranscriptional control mechanisms affecting mRNA stability and translation. Traditional methods of genome wide microarray analysis, profiling steady-state levels of mRNA, may miss important mRNA targets owing to significant posttranscriptional gene regulation by RNA binding proteins (RBPs. Methods The ribonomic approach, utilizing RNA immunoprecipitation hybridized to microarray (RIP-Chip, provides global identification of putative endogenous mRNA targets of different RBPs. HuR is an RBP that binds to the AU-rich elements (ARE of labile mRNAs, such as proto-oncogenes, facilitating their translation into protein. HuR has been shown to play a role in cancer progression and elevated levels of cytoplasmic HuR directly correlate with increased invasiveness and poor prognosis for many cancers, including those of the breast. HuR has been described to control genes in several of the acquired capabilities of cancer and has been hypothesized to be a tumor-maintenance gene, allowing for cancers to proliferate once they are established. Results We used HuR RIP-Chip as a comprehensive and systematic method to survey breast cancer target genes in both MCF-7 (estrogen receptor positive, ER+ and MDA-MB-231 (estrogen receptor negative, ER- breast cancer cell lines. We identified unique subsets of HuR-associated mRNAs found individually or in both cell types. Two novel HuR targets, CD9 and CALM2 mRNAs, were identified and validated by quantitative RT-PCR and biotin pull-down analysis. Conclusion This is the first report of a side-by-side genome-wide comparison of HuR-associated targets in wild type ER+ and ER- breast cancer. We found distinct, differentially expressed subsets of cancer related genes in ER+ and ER- breast cancer cell lines, and noted that the differential regulation of two cancer-related genes by HuR was contingent upon the cellular

  19. Symposium on Differential Geometry and Differential Equations

    CERN Document Server

    Berger, Marcel; Bryant, Robert

    1987-01-01

    The DD6 Symposium was, like its predecessors DD1 to DD5 both a research symposium and a summer seminar and concentrated on differential geometry. This volume contains a selection of the invited papers and some additional contributions. They cover recent advances and principal trends in current research in differential geometry.

  20. Composite Differential Search Algorithm

    Directory of Open Access Journals (Sweden)

    Bo Liu

    2014-01-01

    Full Text Available Differential search algorithm (DS is a relatively new evolutionary algorithm inspired by the Brownian-like random-walk movement which is used by an organism to migrate. It has been verified to be more effective than ABC, JDE, JADE, SADE, EPSDE, GSA, PSO2011, and CMA-ES. In this paper, we propose four improved solution search algorithms, namely “DS/rand/1,” “DS/rand/2,” “DS/current to rand/1,” and “DS/current to rand/2” to search the new space and enhance the convergence rate for the global optimization problem. In order to verify the performance of different solution search methods, 23 benchmark functions are employed. Experimental results indicate that the proposed algorithm performs better than, or at least comparable to, the original algorithm when considering the quality of the solution obtained. However, these schemes cannot still achieve the best solution for all functions. In order to further enhance the convergence rate and the diversity of the algorithm, a composite differential search algorithm (CDS is proposed in this paper. This new algorithm combines three new proposed search schemes including “DS/rand/1,” “DS/rand/2,” and “DS/current to rand/1” with three control parameters using a random method to generate the offspring. Experiment results show that CDS has a faster convergence rate and better search ability based on the 23 benchmark functions.