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Sample records for meningitidis differentially controls

  1. 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

  2. Differential expression of hemoglobin receptor, HmbR, between carriage and invasive isolates of Neisseria meningitidis contributes to virulence: lessons from a clonal outbreak.

    Science.gov (United States)

    Sevestre, Julien; Diene, Seydina M; Aouiti-Trabelsi, Myriam; Deghmane, Ala-Eddine; Tournier, Isabelle; François, Patrice; Caron, François; Taha, Muhamed-Kheir

    2018-04-11

    Carriage and invasion balance in the pathogenesis of Neisseria meningitidis was analyzed during a recent clonal outbreak of meningococcal B in Normandy, France, that offered the opportunity to compare six isolates undistinguable by conventional typing (B:P1.7,16:F3-3/ST-32) isolated from invasive disease or pharyngeal asymptomatic carriage. Data from animal model (transgenic mice rendered susceptible to N. meningitidis infection) showed an absence of virulence for two non-capsulated carriage isolates, an intermediate virulence for two capsulated carriage isolates and a marked virulence for two capsulated invasive isolates. This differential pathogenesis well correlated with whole genome sequencing analysis that clustered together both isolates of each group together, forming their own arm within the Norman cluster. Gene-by-gene analysis specified that genes involved in iron acquisition were among the elements differentially represented in cluster of invasive isolates compared to cluster of capsulated carriage isolates. The hemoglobin receptor encoding gene hmbR was in an ON-phase in the capsulated invasive isolates while carriage capsulated isolates were in an OFF-phase. An ON-phase variant of a capsulated carriage isolate showed enhanced virulence. These data underline the role of phase variation (ON/OFF) of HmbR in the balance between disease isolates/carriage isolates.

  3. Development of an internal amplification control system for a real-time PCR assay for detection of Neisseria meningitidis in CSF and EDTA blood.

    Science.gov (United States)

    McIver, Christopher J; Bell, Sydney M; Er, Noel

    2014-06-01

    The aim of this study was to assemble and assess a non-competitive internal amplification control (IAC) system targeting the Escherichia coli alanine racemase (alr) gene to include in a real-time polymerase chain reaction (PCR) assay for Neisseria meningitidis. Primers and hybridisation probes specific for the IAC were designed and assessed for specificity. Amplification efficiency and limit of detection for the assembled assay was extrapolated using standard curves constructed with serial dilutions of N. meningitidis in saline, pooled cerebrospinal fluid (CSF) and EDTA blood. The 95% confidence limits (CI) were calculated for IAC crossing-points recorded for assays for N. meningitidis ctrA in saline (negative blank), and N. meningitides-negative samples of CSF and EDTA blood. These limits served as a reference range against which the IAC crossing-points recorded for prospective assays are compared to detect sample inhibition. This system was used in testing consecutive EDTA blood samples from two cases of meningococcal disease. The IAC system is specific for Escherichia coli and Shigella species. The amplification efficiency of the assembled assay for N. meningitidis and ability to detect low target DNA levels was not compromised with the inclusion of the IAC system. The IAC crossing-points varied in clinical samples of CSF and EDTA blood. The elucidated reference range for EDTA blood was used to detect sample inhibition in one of the two clinical cases investigated.The IAC system monitors the performance of all processes in the assembled assay for N. meningitidis. Measuring IAC crossing-points serves as an indicator of sample stability and inhibitory properties when testing single or multiple samples from the same patient. Specificity for E. coli and Shigella species enables inclusion in assays of different targets within the same laboratory. Reporting PCR assay results in the context of the IAC crossing-points and reference ranges validates against sample

  4. Could the multicomponent meningococcal serogroup B vaccine (4CMenB) control Neisseria meningitidis capsular group X outbreaks in Africa?

    Science.gov (United States)

    Hong, Eva; Giuliani, Marzia Monica; Deghmane, Ala-Eddine; Comanducci, Maurizio; Brunelli, Brunella; Dull, Peter; Pizza, Mariagrazia; Taha, Muhamed-Kheir

    2013-02-04

    A new vaccine, 4CMenB, is composed of surface proteins of Neisseria meningitidis and is aimed to target serogroup B (MenB) isolates. The vaccine components are present in meningococcal isolates of other serogroups allowing potential use against meningococcal isolates belonging to non-B serogroups. Isolates of serogroup X (MenX) have been emerged in countries of the African meningitis belt. 4CMenB may offer a vaccine strategy against these isolates as there is no available capsule-based vaccine against MenX. We used the Meningococcal Antigen Typing System (MATS) to determine presence, diversity and levels of expression of 4CMenB antigens among 9 MenX isolates from several African countries in order to estimate the potential coverage of MenX by the 4CMenB vaccine. We performed bactericidal assays against these isolates, using pooled sera from 4CMenB-vaccinated infants, adolescents and adults. The African MenX isolates belonged to the same genotype but showed variation in the vaccine antigens. MATS data and bactericidal assays suggest coverage of the 9 African MenX isolates by 4CMenB but not of two unrelated MenX isolates from France. 4CMenB vaccine can be considered for further investigation to control MenX outbreaks in Africa. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Riboregulation in Neisseria meningitidis

    NARCIS (Netherlands)

    Huis in 't Veld, R.A.G.

    2017-01-01

    Neisseria meningitidis (the meningococcus) is primarily a commensal of the human oropharynx that sporadically causes septicemia and meningitis. Meningococci adapt to diverse local host conditions that differ in nutrient supply such as the nasopharynx, blood and cerebrospinal fluid by changing

  6. Infinite dimensional differential games with hybrid controls

    Indian Academy of Sciences (India)

    Differential game; strategy; hybrid controls; value; viscosity solution. 1. Introduction and preliminaries. The study of differential games with Elliott–Kalton strategies in the viscosity solution framework is initiated by Evans and Souganidis [3] where both players are allowed to take continuous controls. Differential games where ...

  7. Expression of phosphofructokinase in Neisseria meningitidis

    NARCIS (Netherlands)

    Baart, G.J.E.; Langenhof, M.; Waterbeemd, van de B.; Hamstra, H.J.; Zomer, B.; Pol, van der L.A.; Beuvery, E.C.; Tramper, J.; Martens, D.E.

    2010-01-01

    Neisseria meningitidis serogroup B is a pathogen that can infect diverse sites within the human host. According to the N. meningitidis genomic information and experimental observations, glucose can be completely catabolized through the Entner–Doudoroff pathway and the pentose phosphate pathway. The

  8. 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

  9. Transcriptional control of t lymphocyte differentiation

    NARCIS (Netherlands)

    F.J.T. Staal (Frank); F. Weerkamp (Floor); A.W. Langerak (Anton); R.W. Hendriks (Rudi); H.C. Clevers (Hans)

    2001-01-01

    textabstractInitiation of gene transcription by transcription factors (TFs) is an important regulatory step in many developmental processes. The differentiation of T cell progenitors in the thymus is tightly controlled by signaling molecules, ultimately activating

  10. Infinite dimensional differential games with hybrid controls

    Indian Academy of Sciences (India)

    Abstract. A two-person 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 maxi- mizing player is allowed to take continuous and switching controls.

  11. 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 ...

  12. Role of Hfq in iron-dependent and -independent gene regulation in Neisseria meningitidis.

    Science.gov (United States)

    Mellin, J R; McClure, Ryan; Lopez, Delia; Green, Olivia; Reinhard, Bjorn; Genco, Caroline

    2010-08-01

    In Neisseria meningitidis, iron-responsive gene regulation is mediated primarily by the ferric uptake regulator (Fur) protein. When complexed with iron, Fur represses gene expression by preventing transcription initiation. Fur can also indirectly activate gene expression via the repression of regulatory small RNAs (sRNA). One such Fur- and iron-regulated sRNA, NrrF, was previously identified in N. meningitidis and shown to repress expression of the sdhA and sdhC genes encoding subunits of the succinate dehydrogenase complex. In the majority of Gram-negative bacteria, sRNA-mediated regulation requires a cofactor RNA-binding protein (Hfq) for proper gene regulation and stabilization. In this study, we examined the role of Hfq in NrrF-mediated regulation of the succinate dehydrogenase genes in N. meningitidis and the effect of an hfq mutation on iron-responsive gene regulation more broadly. We first demonstrated that the stability of NrrF, as well as the regulation of sdhC and sdhA in vivo, was unaltered in the hfq mutant. Secondly, we established that iron-responsive gene regulation of the Fur-regulated sodB gene was dependent on Hfq. Finally, we demonstrated that in N. meningitidis, Hfq functions in a global manner to control expression of many ORFs and intergenic regions via iron-independent mechanisms. Collectively these studies demonstrate that in N. meningitidis, iron- and NrrF-mediated regulation of sdhC and sdhA can occur independently of Hfq, although Hfq functions more globally to control regulation of other N. meningitidis genes primarily by iron-independent mechanisms.

  13. Cell surface control of differentiation in Acanthamoeba.

    Science.gov (United States)

    Yang, S; Villemez, C

    1994-12-01

    Acanthamoeba castellanii (Neff) is a free-living soil amoeba with close relatives that are opportunistic pathogens. Trophozoites differentiate into cysts when deprived of nutrients; cysts convert into trophozoites, leaving the wall behind, in the presence of nutrients. The data presented here, which includes immunoaffinity purification of the receptor, indicate that cell surface molecular signals also control Acanthamoeba differentiation in both directions. Monoclonal antibodies that bind specifically to a 40 kD trophozoite protein initiate the encystment of trophozoites. When bound to cysts the same monoclonal antibodies prevent excystment. Washing away the antibody allows both trophozoites and cysts to resume normal activity. One of these monoclonal antibodies inhibits pinocytosis, while another has no effect on pinocytosis.

  14. Neisseria meningitidis Serogroup W, Burkina Faso, 2012

    OpenAIRE

    MacNeil, Jessica R.; Medah, Isaïe; Koussoubé, Daouda; Novak, Ryan T.; Cohn, Amanda C.; Diomandé, Fabien V.K.; Yelbeogo, Denis; Kambou, Jean Ludovic; Tarbangdo, Tiga F.; Ouédraogo-Traoré, Rasmata; Sangaré, Lassana; Hatcher, Cynthia; Vuong, Jeni; Mayer, Leonard W.; Djingarey, Mamoudou H.

    2014-01-01

    In 2010, Burkina Faso became the first country to introduce meningococcal serogroup A conjugate vaccine (PsA-TT). During 2012, Burkina Faso reported increases in Neisseria meningitidis serogroup W, raising questions about whether these cases were a natural increase in disease or resulted from serogroup replacement after PsA-TT introduction. We analyzed national surveillance data to describe the epidemiology of serogroup W and genotyped 61 serogroup W isolates. In 2012, a total of 5,807 mening...

  15. Deep sequencing whole transcriptome exploration of the σE regulon in Neisseria meningitidis.

    Directory of Open Access Journals (Sweden)

    Robert Antonius Gerhardus Huis in 't Veld

    Full Text Available Bacteria live in an ever-changing environment and must alter protein expression promptly to adapt to these changes and survive. Specific response genes that are regulated by a subset of alternative σ(70-like transcription factors have evolved in order to respond to this changing environment. Recently, we have described the existence of a σ(E regulon including the anti-σ-factor MseR in the obligate human bacterial pathogen Neisseria meningitidis. To unravel the complete σ(E regulon in N. meningitidis, we sequenced total RNA transcriptional content of wild type meningococci and compared it with that of mseR mutant cells (ΔmseR in which σ(E is highly expressed. Eleven coding genes and one non-coding gene were found to be differentially expressed between H44/76 wildtype and H44/76ΔmseR cells. Five of the 6 genes of the σ(E operon, msrA/msrB, and the gene encoding a pepSY-associated TM helix family protein showed enhanced transcription, whilst aniA encoding a nitrite reductase and nspA encoding the vaccine candidate Neisserial surface protein A showed decreased transcription. Analysis of differential expression in IGRs showed enhanced transcription of a non-coding RNA molecule, identifying a σ(E dependent small non-coding RNA. Together this constitutes the first complete exploration of an alternative σ-factor regulon in N. meningitidis. The results direct to a relatively small regulon indicative for a strictly defined response consistent with a relatively stable niche, the human throat, where N. meningitidis resides.

  16. 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.

  17. Evaluation of the induction of immune memory following infant immunisation with serogroup C Neisseria meningitidis conjugate vaccines--exploratory analyses within a randomised controlled trial.

    Science.gov (United States)

    Khatami, Ameneh; Clutterbuck, Elizabeth A; Thompson, Amber J; McKenna, Jennifer A; Pace, David; Birks, Jacqueline; Snape, Matthew D; Pollard, Andrew J

    2014-01-01

    We measured meningococcal serogroup C (MenC)-specific memory B-cell responses in infants by Enzyme-Linked Immunospot (ELISpot) following different MenC conjugate vaccine schedules to investigate the impact of priming on immune memory. Infants aged 2 months were randomised to receive 1 or 2 doses of MenC-CRM197 at 3 or 3 and 4 months, 1 dose of MenC-TT at 3 months, or no primary MenC doses. All children received a Haemophilus influenzae type b (Hib)-MenC booster at 12 months. Blood was drawn at 5, 12, 12 months +6 days and 13 months of age. Results were available for 110, 103, 76 and 44 children from each group respectively. Following primary immunisations, and prior to the 12-month booster, there were no significant differences between 1- or 2-dose primed children in the number of MenC memory B-cells detected. One month following the booster, children primed with 1 dose MenC-TT had more memory B-cells than children primed with either 1-dose (p = 0.001) or 2-dose (pmemory B-cells detected in children who received 1 or 2 doses of MenC-CRM197 in infancy and un-primed children. MenC-specific memory B-cell production may be more dependent on the type of primary vaccine used than the number of doses administered. Although the mechanistic differences between MenC-CRM197 and MenC-TT priming are unclear, it is possible that structural differences, including the carrier proteins, may underlie differential interactions with B- and T-cell populations, and thus different effects on various memory B-cell subsets. A MenC-TT/Hib-MenC-TT combination for priming/boosting may offer an advantage in inducing more persistent antibody. EU Clinical Trials Register 2009-016579-31 ClinicalTrials.gov NCT01129518.

  18. Evaluation of the induction of immune memory following infant immunisation with serogroup C Neisseria meningitidis conjugate vaccines--exploratory analyses within a randomised controlled trial.

    Directory of Open Access Journals (Sweden)

    Ameneh Khatami

    Full Text Available We measured meningococcal serogroup C (MenC-specific memory B-cell responses in infants by Enzyme-Linked Immunospot (ELISpot following different MenC conjugate vaccine schedules to investigate the impact of priming on immune memory.Infants aged 2 months were randomised to receive 1 or 2 doses of MenC-CRM197 at 3 or 3 and 4 months, 1 dose of MenC-TT at 3 months, or no primary MenC doses. All children received a Haemophilus influenzae type b (Hib-MenC booster at 12 months. Blood was drawn at 5, 12, 12 months +6 days and 13 months of age.Results were available for 110, 103, 76 and 44 children from each group respectively. Following primary immunisations, and prior to the 12-month booster, there were no significant differences between 1- or 2-dose primed children in the number of MenC memory B-cells detected. One month following the booster, children primed with 1 dose MenC-TT had more memory B-cells than children primed with either 1-dose (p = 0.001 or 2-dose (p<0.0001 MenC-CRM197. There were no differences in MenC memory B-cells detected in children who received 1 or 2 doses of MenC-CRM197 in infancy and un-primed children.MenC-specific memory B-cell production may be more dependent on the type of primary vaccine used than the number of doses administered. Although the mechanistic differences between MenC-CRM197 and MenC-TT priming are unclear, it is possible that structural differences, including the carrier proteins, may underlie differential interactions with B- and T-cell populations, and thus different effects on various memory B-cell subsets. A MenC-TT/Hib-MenC-TT combination for priming/boosting may offer an advantage in inducing more persistent antibody.EU Clinical Trials Register 2009-016579-31 ClinicalTrials.gov NCT01129518.

  19. Two Neisseria meningitidis strains with different ability to stimulate toll-like receptor 4 through the MyD88-independent pathway

    DEFF Research Database (Denmark)

    Mogensen, T.H.; Paludan, Søren Riis; Kilian, Mogens

    2006-01-01

    Neisseria meningitidis causes acute severe diseases, including sepsis and meningitis, and more benign manifestations such as chronic meningococcemia or colonization of the upper respiratory tract. The inflammatory response, which contributes to the pathogenesis of meningococcal disease......, is initiated by pattern recognition receptors, among which Toll-like receptors (TLR)s have been ascribed a particularly important role. We have previously demonstrated that N. meningitidis induce proinflammatory cytokine expression through TLR2 and TLR4. Here we characterize the molecular basis...... for differential activation of the inflammatory response by two N. meningitidis strains. This difference was due to differential ability to activate signal transduction through TLR4, as HEK293 cells expressing TLR4 produced significantly different levels of interleukin-8 in response to these strains. At the level...

  20. Shifts in the Antibiotic Susceptibility, Serogroups, and Clonal Complexes of Neisseria meningitidis in Shanghai, China: A Time Trend Analysis of the Pre-Quinolone and Quinolone Eras.

    Science.gov (United States)

    Chen, Mingliang; Guo, Qinglan; Wang, Ye; Zou, Ying; Wang, Gangyi; Zhang, Xi; Xu, Xiaogang; Zhao, Miao; Hu, Fupin; Qu, Di; Chen, Min; Wang, Minggui

    2015-06-01

    Fluoroquinolones have been used broadly since the end of the 1980s and have been recommended for Neisseria meningitidis prophylaxis since 2005 in China. The aim of this study was to determine whether and how N. meningitidis antimicrobial susceptibility, serogroup prevalence, and clonal complex (CC) prevalence shifted in association with the introduction and expanding use of quinolones in Shanghai, a region with a traditionally high incidence of invasive disease due to N. meningitidis. A total of 374 N. meningitidis isolates collected by the Shanghai Municipal Center for Disease Control and Prevention between 1965 and 2013 were studied. Shifts in the serogroups and CCs were observed, from predominantly serogroup A CC5 (84%) in 1965-1973 to serogroup A CC1 (58%) in 1974-1985, then to serogroup C or B CC4821 (62%) in 2005-2013. The rates of ciprofloxacin nonsusceptibility in N. meningitidis disease isolates increased from 0% in 1965-1985 to 84% (31/37) in 2005-2013 (p era. Ciprofloxacin should be utilized with caution for the chemoprophylaxis of N. meningitidis in China.

  1. OUTPUT CONTROL WITH ADAPTIVE-PROPORTIONAL DIFFERENTIAL CONTROLLER

    Directory of Open Access Journals (Sweden)

    O. F. Opeiko

    2016-01-01

    Full Text Available The goal of this articl is to improve acсuracy and stability margine for system with proportional differential (PD-controllers and parameters unsertaity by means of adaptation. The adaptive controller must produce the accuraсy improving by encreasing the proportional gain of controller, when the error is non zero. Consequently, the error decrease, adaptation become less intensive, and the system maintain the stability. The is provided by the correctly constructed Lapunov function. The method of parametric synthesis for adaptive PD-controller is developed based on roots location on complex plane. The numerical example of synthesis is presented with simulation results, which demonstrate the correctness of developed method. The adaptive PD-controller allow accuracy improuving with stability retaining, i. e. the adaptivity is able to replace the integrator by proportional gain tuning. The adaptive PD-controller is especially helpful for systems, working with inputs variability, and when the exponential dynamic is of importance. In cases, when diturbances are restricted, the adaptive PD-controller provides the stability and accuracy, but slowly operation.

  2. Multistructural biomimetic substrates for controlled cellular differentiation

    International Nuclear Information System (INIS)

    Orza, Anamaria I; Kanarpardy, Ganesh K; Biris, Alexandru S; Mihu, Carmen; Soritau, Olga; Diudea, Mircea; Florea, Adrian; Matei, Horea; Balici, Stefana; Mudalige, Thilak

    2014-01-01

    Multidimensional scaffolds are considered to be ideal candidates for regenerative medicine and tissue engineering based on their potential to provide an excellent microenvironment and direct the fate of the cultured cells. More recently, the use of stem cells in medicine has opened a new technological opportunity for controlled tissue formation. However, the mechanism through which the substrate directs the differentiation of stem cells is still rather unclear. Data concerning its specific surface chemistry, topology, and its signaling ability need to be further understood and analyzed. In our study, atomic force microscopy was used to study the stiffness, roughness, and topology of the collagen (Coll) and metallized collagen (MC) substrates, proposed as an excellent substrate for regenerative medicine. The importance of signaling molecules was studied by constructing a new hybrid signaling substrate that contains both collagen and laminin extracellular matrix (ECM) proteins. The cellular response—such as attachment capability, proliferation and cardiac and neuronal phenotype expression on the metallized and non-metallized hybrid substrates (collagen + laminin)—was studied using MTT viability assay and immunohistochemistry studies. Our findings indicate that such hybrid materials could play an important role in the regeneration of complex tissues. (paper)

  3. Meningitis neonatal por Neisseria meningitidis serogrupo B

    Directory of Open Access Journals (Sweden)

    Manuel Díaz Álvarez

    Full Text Available La meningitis meningocóccica es una infección poco frecuente en el período neonatal internacionalmente, y solo hay una publicación previa en la literatura médica cubana hace 25 años atrás, de recién nacidos con meningitis bacteriana causada por Neisseria meningitidis. Se presenta el caso de un recién nacido febril, con manifestaciones de toxicidad, fontanela abombada, y cuando se realizó punción lumbar, se encontró pleocitosis del líquido cefalorraquídeo y se aisló N. meningitidis serogrupo B, por lo que se diagnostica meningitis meningocóccica neonatal. Tuvo evolución favorable. Se describen algunas características de la infección meningocócica, y se destaca el diagnóstico y tratamiento recomendado para este tipo de infección, así como se hace referencia a reportes de casos publicados en la literatura internacional.

  4. Metabolism and virulence in Neisseria meningitidis

    Directory of Open Access Journals (Sweden)

    Christoph eSchoen

    2014-08-01

    Full Text Available A longstanding question in infection biology addresses the genetic basis for invasive behaviour in commensal pathogens. A prime example for such a pathogen is Neisseria meningitidis. On the one hand it is a harmless commensal bacterium exquisitely adapted to humans, and on the other hand it sometimes behaves like a ferocious pathogen causing potentially lethal disease such as sepsis and acute bacterial meningitis. Despite the lack of a classical repertoire of virulence genes in N. meningitidis separating commensal from invasive strains, molecular epidemiology suggests that carriage and invasive strains belong to genetically distinct populations. In recent years, it has become increasingly clear that metabolic adaptation enables meningococci to exploit host resources, supporting the concept of nutritional virulence as a crucial determinant of invasive capability. Here, we discuss the contribution of core metabolic pathways in the context of colonization and invasion with special emphasis on results from genome-wide surveys. The metabolism of lactate, the oxidative stress response, and, in particular, glutathione metabolism as well as the denitrification pathway provide examples of how meningococcal metabolism is intimately linked to pathogenesis. We further discuss evidence from genome-wide approaches regarding potential metabolic differences between strains from hyperinvasive and carriage lineages and present new data assessing in vitro growth differences of strains from these two populations. We hypothesize that strains from carriage and hyperinvasive lineages differ in the expression of regulatory genes involved particularly in stress responses and amino acid metabolism under infection conditions.

  5. Neisseria meningitidis serogroup W, Burkina Faso, 2012.

    Science.gov (United States)

    MacNeil, Jessica R; Medah, Isaïe; Koussoubé, Daouda; Novak, Ryan T; Cohn, Amanda C; Diomandé, Fabien V K; Yelbeogo, Denis; Kambou, Jean Ludovic; Tarbangdo, Tiga F; Ouédraogo-Traoré, Rasmata; Sangaré, Lassana; Hatcher, Cynthia; Vuong, Jeni; Mayer, Leonard W; Djingarey, Mamoudou H; Clark, Thomas A; Messonnier, Nancy E

    2014-03-01

    In 2010, Burkina Faso became the first country to introduce meningococcal serogroup A conjugate vaccine (PsA-TT). During 2012, Burkina Faso reported increases in Neisseria meningitidis serogroup W, raising questions about whether these cases were a natural increase in disease or resulted from serogroup replacement after PsA-TT introduction. We analyzed national surveillance data to describe the epidemiology of serogroup W and genotyped 61 serogroup W isolates. In 2012, a total of 5,807 meningitis cases were reported through enhanced surveillance, of which 2,353 (41%) were laboratory confirmed. The predominant organism identified was N. meningitidis serogroup W (62%), and all serogroup W isolates characterized belonged to clonal complex 11. Although additional years of data are needed before we can understand the epidemiology of serogroup W after PsA-TT introduction, these data suggest that serogroup W will remain a major cause of sporadic disease and has epidemic potential, underscoring the need to maintain high-quality case-based meningitis surveillance after PsA-TT introduction.

  6. Fournier’s Gangrene in a Heterosexual Man: A Complication of Neisseria meningitidis Urethritis

    Directory of Open Access Journals (Sweden)

    Tariq A. Khemees

    2012-01-01

    Full Text Available A 55-year-old heterosexual male presented to the emergency department with a symptomatology consistent with urethritis and Fournier’s gangrene. Urethral swab and operative tissue cultures were positive for coagulase-negative Staphylococcus and an intracellular Gram-negative diplococcus. The latter was initially thought to be Neisseria gonorrhea; however, DNA sequencing technique confirmed it to be Neisseria meningitidis. The patient required three separate surgical debridements to control widespread necrotizing infection. Following documentation of sterile wound healing with appropriate antibiotics, four reconstructive surgeries were necessary to manage the resultant wound defects. To our knowledge, Neisseria meningitidis as a causative organism in Fournier’s gangrene has not been reported in the literature.

  7. Subclinical infection of the genital tract with Neisseria meningitidis

    Directory of Open Access Journals (Sweden)

    Maria Cristina S. Lourenço

    Full Text Available We report the isolation of Neisseria meningitidis, characterized as B:NT:P1.7, from a female patient's genital tract in an outpatient clinic for HIV care. The gynecology clinic, as part of the follow up, collects specimens from all patients with HIV infection for routine exams and for early laboratory detection of sexually transmitted diseases . A Gram-negative diplococcus was isolated from the cervix of a heterosexual patient with AIDS. Based on this and other reported cases, urogenital infection with N. meningitidis can no longer be considered uncommon. The rising incidence of N. meningitidis isolated from this and similar sites has significant medical and diagnostic implications.

  8. Theory of control systems described by differential inclusions

    CERN Document Server

    Han, Zhengzhi; Huang, Jun

    2016-01-01

    This book provides a brief introduction to the theory of finite dimensional differential inclusions, and deals in depth with control of three kinds of differential inclusion systems. The authors introduce the algebraic decomposition of convex processes, the stabilization of polytopic systems, and observations of Luré systems. They also introduce the elemental theory of finite dimensional differential inclusions, and the properties and designs of the control systems described by differential inclusions. Addressing the material with clarity and simplicity, the book includes recent research achievements and spans all concepts, concluding with a critical mathematical framework. This book is intended for researchers, teachers and postgraduate students in the area of automatic control engineering.

  9. Neisseria meningitidis serogroup A capsular polysaccharide acetyltransferase, methods and compositions

    Energy Technology Data Exchange (ETDEWEB)

    Stephens, David S [Stone Mountain, GA; Gudlavalleti, Seshu K [Kensington, MD; Tzeng, Yih-Ling [Atlanta, GA; Datta, Anup K [San Diego, CA; Carlson, Russell W [Athens, GA

    2011-02-08

    Provided are methods for recombinant production of an O-acetyltransferase and methods for acetylating capsular polysaccharides, especially those of a Serogroup A Neisseria meningitidis using the recombinant O-acetyltransferase, and immunogenic compositions comprising the acetylated capsular polysaccharide.

  10. Survival of Neisseria meningitidis outside of the host: environmental effects and differences among strains.

    Science.gov (United States)

    Swain, C L; Martin, D R; Sim, D; Jordan, T W; Mackichan, J K

    2017-12-01

    Neisseria meningitidis is a gram-negative bacterium that lives as a commensal in the human nasopharynx. Meningococci are generally non-invasive, but can invade the nasopharyngeal epithelia and enter the bloodstream causing life-threatening illnesses. It is generally thought that meningococci do not survive for long outside the host, and that transmission requires relatively close contact between hosts. There are some reports, however, that meningococci can survive drying on surfaces, including glass, plastic and cloth. Our examination of N. meningitidis strains dried on glass showed differences in survival of isolates belonging to serogroups B, C and W135, including persistence of Cuban, New Zealand, and Norwegian epidemic strains up to 8 days, depending on temperature and humidity. Survival of a New Zealand epidemic strain isolate NZ98/254 under ambient conditions in the laboratory was greatest in winter suggesting that environmental factors impacted survival. For most isolates, including NZ98/254, survival under controlled conditions at 30 °C was greater at 22% than 30% relative humidity. There were also some differences in survival between carriage and invasive strains. The results suggest that N. meningitidis could be transmitted through contact with surfaces outside the host, potentially including contact through shared drinking vessels.

  11. 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.

  12. Characterization of the Neisseria meningitidis Helicase RecG.

    Directory of Open Access Journals (Sweden)

    Getachew Tesfaye Beyene

    Full Text Available Neisseria meningitidis (Nm is a Gram-negative oral commensal that opportunistically can cause septicaemia and/or meningitis. Here, we overexpressed, purified and characterized the Nm DNA repair/recombination helicase RecG (RecGNm and examined its role during genotoxic stress. RecGNm possessed ATP-dependent DNA binding and unwinding activities in vitro on a variety of DNA model substrates including a Holliday junction (HJ. Database searching of the Nm genomes identified 49 single nucleotide polymorphisms (SNPs in the recGNm including 37 non-synonymous SNPs (nsSNPs, and 7 of the nsSNPs were located in the codons for conserved active site residues of RecGNm. A transient reduction in transformation of DNA was observed in the Nm ΔrecG strain as compared to the wildtype. The gene encoding recGNm also contained an unusually high number of the DNA uptake sequence (DUS that facilitate transformation in neisserial species. The differentially abundant protein profiles of the Nm wildtype and ΔrecG strains suggest that expression of RecGNm might be linked to expression of other proteins involved in DNA repair, recombination and replication, pilus biogenesis, glycan biosynthesis and ribosomal activity. This might explain the growth defect that was observed in the Nm ΔrecG null mutant.

  13. SENSITIVITAS KUMAN NEISSERIA MENINGITIDIS YANG DIISOLASI DARI JAMAAH HAJI INDONESIA TERHADAP BEBERAPA ANTIBIOTIK

    Directory of Open Access Journals (Sweden)

    Muljati Prijanto

    2012-09-01

    Full Text Available The meningitis meningococcal disease caused by Neisseriae meningitidis is an infection of meninges and cerebrospinal fluid (CSF of the brain and the spinal cord. N. meningitidis is classified into 13 serogroups based on the immunologic reactivity of the capsular polysaccharide. Since 1993 the number of cases and carriers of haj pilgrims from Indonesia have increased. In 1996 the carrier rate was 9,4%, and case fatality rate of Indonesian haj pilgrims in Saudi Arabia was 71,4%. The dominant serogroup was serogroup B. The meningitis vaccine of serogroup B is not available yet. Until now there is not enough information of the laboratory results from the hospital in Saudi Arabia, regarding the strain that caused the infection of haj pilgrims from Indonesia. To prevent transmission of the disease among Haj pilgrims, since 1997, chemoprophylaxis with ciprofloxacine has been given to close contact persons of haj pilgrim patient. The objectives of this study are: First, to know the effectiveness of ciprofloxacin in decreasing the carrier rate of meningitis meningococcus in haj pilgrims. Second, to identify the serogroup of N. meningitidis isolated from carrier or patient and thirdly to know the sensitivity of bacteria to several antibiotics recommended by WHO. Nasofaringeal swabs were taken from 914 haj pilgrims from group of contact person of cases or suspected cases and 311 haj pilgrims from control group at embarkation in Jakarta. Ciprofloxacin was given to the study group in Saudi Arabia. Isolation and serogrouping were carried out for serogroup A, B, C. The result shows that the effectiveness of ciprofloxacin to N. meningitidis in the treated group were 98.58% and control were 85.54%, respectively. The serogroup of N. meningitidis is isolated from 13 carriers of treated group 69,23% could not be classified as serogroup A, B, or C. In the control group, 45 isolated strains from carriers consist of serogroup B 40%, serogroup C 28,9%, serogroup A 20

  14. High-order nonlinear differentiator and application to aircraft control

    Science.gov (United States)

    Wang, Xinhua; Shirinzadeh, Bijan

    2014-06-01

    In this paper, a high-order continuous nonlinear differentiator with lead compensation is presented based on finite-time stability. Not only the proposed high-order nonlinear differentiator can obtain the high-order derivatives of a signal, but also the chattering phenomenon can be reduced sufficiently. The parameters regulation is only required to be satisfied with Routh-Hurwitz Stability Criterion. The presented differentiator is a generalization of sliding mode differentiator and linear high-gain differentiator. The merits of the continuous differentiator include its simplicity, selecting parameters easily, restraining noises sufficiently, decreasing the phase shift and avoiding the chattering phenomenon. The theoretical results are confirmed by computer simulations and an experiment on a quadrotor aircraft: (i) the estimation of flying velocity and acceleration from the position measurement; (ii) a control law is designed based on the presented nonlinear differentiator to track a reference trajectory.

  15. Differential Aspects of Locus of Control and Attitudes Towards Death.

    Science.gov (United States)

    Hyams, Nanci Barbara; And Others

    1982-01-01

    Investigated the relationship between locus of control and death anxiety in 99 college students. Results indicated a significant relationship between external locus of control and concern about death, and a specific differential patterning between locus of control and death anxiety. Sex differences existed on four locus of control dimensions. (WAS)

  16. 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

  17. Recombinant outer membrane secretin PilQ(406-770) as a vaccine candidate for serogroup B Neisseria meningitidis.

    Science.gov (United States)

    Haghi, Fakhri; Peerayeh, Shahin Najar; Siadat, Seyed Davar; Zeighami, Habib

    2012-02-21

    Secretin PilQ is an antigenically conserved outer membrane protein which is present on most meningococci. This protein naturally expressed at high levels and is essential for meningococcal pilus expression at the cell surface. A 1095 bp fragment of C-terminal of secretin pilQ from serogroup B Neisseria meningitidis was cloned into prokaryotic expression vector pET-28a. Recombinant protein was overexpressed with IPTG and affinity-purified by Ni-NTA agarose. BALB/c mice were immunized subcutaneously with purified rPilQ(406-770) mixed with Freund's adjuvant. Serum antibody responses to serogroups A and B N. meningitidis whole cells or purified rPilQ(406-770) and functional activity of antibodies were determined by ELISA and SBA, respectively. The output of rPilQ(406-770) was approximately 50% of the total bacterial proteins. Serum IgG responses were significantly increased in immunized group with PilQ(406-770) mixed with Freund's adjuvant in comparison with control groups. Antisera produced against rPilQ(406-770) demonstrated strong surface reactivity to serogroups A and B N. meningitidis tested by whole-cell ELISA. Surface reactivity to serogroup B N. meningitidis was higher than serogroup A. The sera from PilQ(406-770) immunized animals were strongly bactericidal against serogroups A and B. These results suggest that rPilQ(406-770) is a potential vaccine candidate for serogroup B N. meningitidis. Copyright © 2011 Elsevier Ltd. All rights reserved.

  18. Comparison of dot-ELISA and standard ELISA for detection of Neisseria meningitidis outer membrane complex-specific antibodies

    Directory of Open Access Journals (Sweden)

    Elza FT Belo

    Full Text Available Dot-ELISA using the outer membrane complex antigens of Neisseria meningitidis as a target was standardized for rapid detection of meningococcal-specific antibodies in human serum. We investigated the level of meningococcal-specific IgG, IgA, and IgM in serum using dot-ELISA with outer membrane antigens prepared from Neisseria meningitidis serotype B:4.19:P1.15,3,7,9 (a strain isolated from a Brazilian epidemic. The dot-ELISA is based on the same principles as the standard ELISA and is useful for detection of anti-N. meningitidis B antibodies in serum of patients with meningococcal infections. For the assay, outer membrane complexes (OMCs were absorbed by nitrocellulose membrane and blocked with a 5% skim milk solution. Serum samples were drawn upon hospital admission and during convalescence from patients with meningococcal septicemia, and single samples were drawn from uninfected controls. We retrospectively examined a total of 57 serum samples: 35 from patients infected with N. meningitidis B, 12 from patients infected with Haemophilus influenzae b, and 10 from health individuals. When performed at room temperature, dot-ELISA took approximately four hours to perform, and the optimum antigen concentration was 0.42 µg per dot. The specificity of IgG, IgM, and IgA demonstrates that dot-ELISA using OMCs from N. meningitidis B as a target is suitable for serologic verification of clinically suspected meningococcal disease in patients and for titer determination of antibodies produced during different phases of natural infection. Furthermore, the sensitivity of dot-ELISA was comparable to that of standard ELISA. Overall, dot-ELISA is simple to perform, rapid, and low cost. Further validation of the test as a screening tool is required.

  19. approximate controllability of a non-autonomous differential equation

    Indian Academy of Sciences (India)

    53

    controllability results of a semilinear control system by assuming monotonicity con- ditions on the nonlinear part. Dauer and Mahmudov [7] studied the approximate controllability of functional differential equation by using the Schauder fixed point theorem when the semigroup is compact, and the Banach fixed theorem when ...

  20. Temperature triggers immune evasion by Neisseria meningitidis.

    Science.gov (United States)

    Loh, Edmund; Kugelberg, Elisabeth; Tracy, Alexander; Zhang, Qian; Gollan, Bridget; Ewles, Helen; Chalmers, Ronald; Pelicic, Vladimir; Tang, Christoph M

    2013-10-10

    Neisseria meningitidis has several strategies to evade complement-mediated killing, and these contribute to its ability to cause septicaemic disease and meningitis. However, the meningococcus is primarily an obligate commensal of the human nasopharynx, and it is unclear why the bacterium has evolved exquisite mechanisms to avoid host immunity. Here we demonstrate that mechanisms of meningococcal immune evasion and resistance against complement increase in response to an increase in ambient temperature. We have identified three independent RNA thermosensors located in the 5' untranslated regions of genes necessary for capsule biosynthesis, the expression of factor H binding protein, and sialylation of lipopolysaccharide, which are essential for meningococcal resistance against immune killing. Therefore increased temperature (which occurs during inflammation) acts as a 'danger signal' for the meningococcus, enhancing its defence against human immune killing. Infection with viral pathogens, such as influenza, leads to inflammation in the nasopharynx with an increased temperature and recruitment of immune effectors. Thermoregulation of immune defence could offer an adaptive advantage to the meningococcus during co-infection with other pathogens, and promote the emergence of virulence in an otherwise commensal bacterium.

  1. Genomic Characterization of Urethritis-Associated Neisseria meningitidis Shows that a Wide Range of N. meningitidis Strains Can Cause Urethritis.

    Science.gov (United States)

    Ma, Kevin C; Unemo, Magnus; Jeverica, Samo; Kirkcaldy, Robert D; Takahashi, Hideyuki; Ohnishi, Makoto; Grad, Yonatan H

    2017-12-01

    Neisseria meningitidis , typically a resident of the oro- or nasopharynx and the causative agent of meningococcal meningitis and meningococcemia, is capable of invading and colonizing the urogenital tract. This can result in urethritis, akin to the syndrome caused by its sister species, N. gonorrhoeae , the etiologic agent of gonorrhea. Recently, meningococcal strains associated with outbreaks of urethritis were reported to share genetic characteristics with the gonococcus, raising the question of the extent to which these strains contain features that promote adaptation to the genitourinary niche, making them gonococcus-like and distinguishing them from other N. meningitidis strains. Here, we analyzed the genomes of 39 diverse N. meningitidis isolates associated with urethritis, collected independently over a decade and across three continents. In particular, we characterized the diversity of the nitrite reductase gene ( aniA ), the factor H-binding protein gene ( fHbp ), and the capsule biosynthetic locus, all of which are loci previously suggested to be associated with urogenital colonization. We observed notable diversity, including frameshift variants, in aniA and fHbp and the presence of intact, disrupted, and absent capsule biosynthetic genes, indicating that urogenital colonization and urethritis caused by N. meningitidis are possible across a range of meningococcal genotypes. Previously identified allelic patterns in urethritis-associated N. meningitidis strains may reflect genetic diversity in the underlying meningococcal population rather than novel adaptation to the urogenital tract. Copyright © 2017 American Society for Microbiology.

  2. Enfermedad por meningococo, Neisseria meningitidis: perspectiva epidemiológica, clínica y preventiva Meningococcal disease caused by Neisseria meningitidis: epidemiological, clinical, and preventive perspectives

    Directory of Open Access Journals (Sweden)

    Lourdes Almeida-González

    2004-10-01

    Full Text Available La meningitis bacteriana continúa siendo uno de los grandes problemas de la salud pública mundial. En particular, la infección por Neisseria meningitidis afecta tanto a países desarrollados como subdesarrollados, y se presenta en formas endémicas y epidémicas. La enfermedad meningocóccica se puede manifestar clínicamente no sólo como meningitis, sino con cuadros fulminantes de meningococcemia. La persistencia de N. meningitidis se debe al gran porcentaje de portadores y a la dinámica de transmisión de la bacteria. Aproximadamente 500 millones de personas en el mundo son portadoras de N. meningitidis en la nasofaringe. Los factores de transmisiblidad identificados han sido el tabaquismo activo o pasivo, la presencia de infecciones virales del tracto respiratorio superior, épocas de sequía, y el hacinamiento. Por lo anterior, se han descrito brotes de enfermedad meningocóccica en cuarteles militares, escuelas, cárceles y dormitorios. Algunos determinantes que permiten la invasión sistémica incluyen daños en la mucosa nasofaríngea de portadores, cepas virulentas con formación de cápsula, ausencia de anticuerpos bactericidas y deficiencias del sistema del complemento. El control de la enfermedad meningocóccica en circunstancias endémicas y epidémicas se logra por el tratamiento de casos con antibióticos adecuados (penicilina, ceftriaxona o cloranfenicol, la quimioprofilaxis de contactos cercanos (ciprofloxacina, rifampicina o ceftriaxona, y la vigilancia clínica de éstos. Sin embargo, es fundamental subrayar que la clave para el control efectivo de la enfermedad meningocóccica es la inmunoprofilaxis. Las vacunas disponibles incluyen las de polisacáridos monovalentes o bivalentes (serogrupos A y C, tetravalentes (A, C, Y, W-135, la conjugada (C o la combinada de proteínas de membrana celular y polisacárido (B y C. Recientemente nos hemos visto forzados a establecer planes nacionales de respuesta que incluyen la

  3. Neisseria meningitidis serogroup C sepsis and septic arthritis in an HIV-positive man.

    Science.gov (United States)

    Fox-Lewis, A; Eades, C P; Manson, J J; Morris-Jones, S; Miller, R F

    2017-08-01

    A patient with well-controlled HIV-1 infection presented with fever and rigors, a widespread maculopapular rash, and severe generalised arthralgia. Sepsis of unknown aetiology was diagnosed, and treatment with broad-spectrum antimicrobials commenced. Following initial clinical improvement, a right knee septic arthritis developed. Microscopy and culture of the joint aspirate were negative for organisms but 16S rDNA PCR identified Neisseria meningitidis DNA, subsequently verified as capsular genogroup C, thus confirming a diagnosis of disseminated meningococcal sepsis with secondary septic arthritis.

  4. 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...

  5. 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.

  6. Meningitis caused by a lipopolysaccharide deficient Neisseria meningitidis

    NARCIS (Netherlands)

    Piet, Jurgen R; Zariri, Afshin; Fransen, Floris; Schipper, Kim; van der Ley, Peter; van de Beek, Diederik; van der Ende, Arie; van Putten, Jos

    2014-01-01

    OBJECTIVE: Lipopolysaccharide (LPS) is a major component of the Neisseria meningitidis outer membrane. Here we report a patient with meningococcal meningitis of which the causative isolate lacked LPS. Thus far, no naturally occurring LPS-deficient meningococcal isolate has been known to cause

  7. Neisseria meningitidis. Lipopolysakkariders patofysiologiske rolle ved meningokoksygdom og septisk shock

    DEFF Research Database (Denmark)

    Pedersen, Mie Østergaard; Pedersen, Dan Sonne; Pedersen, Michael

    2008-01-01

    A major pro-inflammatory and toxic component of N. meningitidis is lipopolysaccharide (LPS). LPS contributes to severe symptoms of meningococcal disease, septic shock and severe coagulopathy, in part by increasing pro-inflammatory mechanisms and reactive oxygen species. Recent technologies have...

  8. Portadores nasofaríngeos de Neisseria meningitidis en trabajadores con riesgo ocupacional

    Directory of Open Access Journals (Sweden)

    Isabel Martínez

    2010-04-01

    Full Text Available Los portadores de Neisseria meningitidis constituyen la principal fuente de infección y transmisión de la enfermedad meningocócica. Conocer su prevalencia, las características de las cepas aisladas y los factores de riesgos asociados con el estado de portador, aportan datos valiosos al control y vigilancia epidemiológica de esta entidad clínica. Para cumplimentar los objetivos propuestos se realizó un estudio transversal descriptivo de portadores de N. meningitidis en 112 trabajadores de un centro de producción de biofarmacéuticos de La Habana, con edades comprendidas entre 18_60 años. Previo a su realización se cumplió con las exigencias bioéticas requeridas para este tipo de estudio. A todos se les realizó un exudado nasofaríngeo y una encuesta, donde se indagó sobre factores de riesgo (edad, sexo, hacinamiento, hábito de fumar, consumo de bebidas alcohólicas, amigdalectomía y antecedentes de infección respiratoria que favorecen la condición del portador. La identificación de las cepas de N. meningitidis se realizó según métodos convencionales, la clasificación de los serogrupos se hizo por aglutinación en láminas portaobjetos con antisueros comerciales y para la identificación de los serotipos y subtipos se empleó un ensayo inmunoenzimático (ELISA de células enteras con anticuerpos monoclonales. Se detectó un 8% de portadores de N. meningitidis con predominio del serogrupo B (77,8% y el fenotipo más frecuente fue el B:4:P1.4 (33,3%. Al analizar el estado de portador y su asociación con los factores de riesgo, la edad (p = 0,05 y el sexo (p = 0,013 mostraron diferencias significativas. Se demostró la posibilidad del riesgo ocupacional en aquellos individuos que por su profesión están en contacto con microorganismos patógenos

  9. Control of matric water potential by temperature differential

    Science.gov (United States)

    Palmer, R. J. Jr; Nienow, J. A.; Friedmann, E. I.

    1987-01-01

    A method for controlling relative humidity based on temperature differentials, rather than on salt solutions, is described. This method has the following advantages: (1) it does not exhibit the anomalous CO2 solution effects that we have found to occur with salt solutions; (2) humidity is continuously adjustable without sample removal; (3) circulation of the atmosphere results in short equilibration times.

  10. A Path Analytic Examination of Differential Social Control Theory.

    Science.gov (United States)

    Ried, L. Douglas

    1989-01-01

    Used path analytic techniques to analyze differential social control theory as predictor of drug use among fifth-eighth grade students (N=860). Found that peer non-use expectations had largest effect on drug use and were directly influenced by parental, peer, and school attachments. (Author/CM)

  11. 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.

  12. 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.

  13. Expansion of a urethritis-associated Neisseria meningitidis clade in the United States with concurrent acquisition of N. gonorrhoeae alleles.

    Science.gov (United States)

    Retchless, Adam C; Kretz, Cécilia B; Chang, How-Yi; Bazan, Jose A; Abrams, A Jeanine; Norris Turner, Abigail; Jenkins, Laurel T; Trees, David L; Tzeng, Yih-Ling; Stephens, David S; MacNeil, Jessica R; Wang, Xin

    2018-03-02

    Increased reports of Neisseria meningitidis urethritis in multiple U.S. cities during 2015 have been attributed to the emergence of a novel clade of nongroupable N. meningitidis within the ST-11 clonal complex, the "U.S. NmNG urethritis clade". Genetic recombination with N. gonorrhoeae has been proposed to enable efficient sexual transmission by this clade. To understand the evolutionary origin and diversification of the U.S. NmNG urethritis clade, whole-genome phylogenetic analysis was performed to identify its members among the N. meningitidis strain collection from the Centers for Disease Control and Prevention, including 209 urogenital and rectal N. meningitidis isolates submitted by U.S. public health departments in eleven states starting in 2015. The earliest representatives of the U.S. NmNG urethritis clade were identified from cases of invasive disease that occurred in 2013. Among 209 urogenital and rectal isolates submitted from January 2015 to September 2016, the clade accounted for 189/198 male urogenital isolates, 3/4 female urogenital isolates, and 1/7 rectal isolates. In total, members of the clade were isolated in thirteen states between 2013 and 2016, which evolved from a common ancestor that likely existed during 2011. The ancestor contained N. gonorrhoeae-like alleles in three regions of its genome, two of which may facilitate nitrite-dependent anaerobic growth during colonization of urogenital sites. Additional gonococcal-like alleles were acquired as the clade diversified. Notably, one isolate contained a sequence associated with azithromycin resistance in N. gonorrhoeae, but no other gonococcal antimicrobial resistance determinants were detected. Interspecies genetic recombination contributed to the early evolution and subsequent diversification of the U.S. NmNG urethritis clade. Ongoing acquisition of N. gonorrhoeae alleles by the U.S. NmNG urethritis clade may facilitate the expansion of its ecological niche while also increasing the

  14. Community cluster of meningococcal disease by Neisseria meningitidis serogroup C in Andalusia, Spain, March to May 2011.

    Science.gov (United States)

    Mayoral Cortés, J M; Torres Butrón, E; García Fernández, M; Herrador Ortiz, Z; Huarte Osakar, S; Santos Luque, R; Pérez Morilla, E; Guillén Enriquez, J

    2012-09-06

    Between March and May of 2011, a cluster of three fatal cases of meningococcal sepsis occurred in Andalusia, Spain, in a municipality with a population of around 20,000 inhabitants. The cases were in their mid-teens to early thirties and were notified to the epidemiological surveillance system of Andalusia (Sistema de Vigilancia Epidemiológica de Andalucía, SVEA) during a 68-day period from March through May 2011. All three were infected with the same strain of Neisseria meningitidis serogroup C genosubtype VR1:5-1;VR2:10-8. None of the cases had been previously vaccinated against N. meningitidis serogroup C. Antibiotic post-exposure chemoprophylaxis was administered to close contacts of every diagnosed case. Once the cluster was confirmed, the local population was informed through the media about the control measures taken by the health authorities. The vaccination history against N. meningitidis serogroup C of the population under 25 years-old in the municipality was checked. Vaccination was offered to unimmunised individuals younger than 25 years of age and an additional dose of vaccine was offered to those who had been vaccinated between 2000 and 2006 with a vaccination schedule of three doses before the first year of age. No further cases occurred since the beginning of these actions.

  15. 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.

  16. Parameter and state estimation in a Neisseria meningitidis model: A study case of Niger

    Science.gov (United States)

    Bowong, S.; Mountaga, L.; Bah, A.; Tewa, J. J.; Kurths, J.

    2016-12-01

    Neisseria meningitidis (Nm) is a major cause of bacterial meningitidis outbreaks in Africa and the Middle East. The availability of yearly reported meningitis cases in the African meningitis belt offers the opportunity to analyze the transmission dynamics and the impact of control strategies. In this paper, we propose a method for the estimation of state variables that are not accessible to measurements and an unknown parameter in a Nm model. We suppose that the yearly number of Nm induced mortality and the total population are known inputs, which can be obtained from data, and the yearly number of new Nm cases is the model output. We also suppose that the Nm transmission rate is an unknown parameter. We first show how the recruitment rate into the population can be estimated using real data of the total population and Nm induced mortality. Then, we use an auxiliary system called observer whose solutions converge exponentially to those of the original model. This observer does not use the unknown infection transmission rate but only uses the known inputs and the model output. This allows us to estimate unmeasured state variables such as the number of carriers that play an important role in the transmission of the infection and the total number of infected individuals within a human community. Finally, we also provide a simple method to estimate the unknown Nm transmission rate. In order to validate the estimation results, numerical simulations are conducted using real data of Niger.

  17. 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

  18. 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.

  19. Optimal control of causal differential-algebraic systems

    Czech Academy of Sciences Publication Activity Database

    Roubíček, Tomáš; Valášek, M.

    2002-01-01

    Roč. 269, č. 2 (2002), s. 616-641 ISSN 0022-247X R&D Projects: GA AV ČR IAA1075005; GA ČR GA201/00/0768 Institutional research plan: CEZ:AV0Z1075907 Keywords : optimal control * differential-algebraic equations * existence theory Subject RIV: BA - General Mathematics Impact factor: 0.458, year: 2002

  20. Growth control and differentiation in mammary epithelial cells.

    OpenAIRE

    Borellini, F; Oka, T

    1989-01-01

    Growth and differentiation of the mammary gland are controlled by various hormones and other environmental factors. The role of hormones and growth factors in mammary development is discussed with regard to animal species, physiological stages, and the various experimental systems in vitro. In the female embryo, mammary morphogenesis is induced by the mesenchyme and is hormone independent, whereas androgens cause the partial necrosis of mammary epithelium in the male. Ductal growth during ado...

  1. Structural, functional and immunogenic insights on Cu,Zn Superoxide Dismutase pathogenic virulence factors from Neisseria meningitidis and Brucella abortus

    Science.gov (United States)

    Bacterial pathogens Neisseria meningitidis and Brucella abortus pose threats to human and animal health worldwide, causing meningococcal disease and brucellosis, respectively. Mortality from acute N. meningitidis infections remains high despite antibiotics, and brucellosis presents alimentary and he...

  2. 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

  3. 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

  4. Live Streptococcus pneumoniae, Haemophilus influenzae, and Neisseria meningitidis activate the inflammatory response trhough Toll-like receptors 2, 4, and 9 in species-specific patterns

    DEFF Research Database (Denmark)

    Mogensen, T.H.; Paludan, Søren Riis; Kilian, Mogens

    2006-01-01

    activation by live bacteria. Here, we demonstrate that live Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis, the three principal causes of bacterial meningitis, use distinct sets of TLRs to trigger the inflammatory response. Using human embryonic kidney 293 cell lines......, each overexpressing one type of TLR, we found that S. pneumoniae triggered activation of the transcription factor nuclear factor-kappaB and expression of interleukin-8, only in cells expressing TLR2 or -9. The same response was evoked by H. influenzae in cells expressing TLR2 or -4 and by N...... and confirmed the essential role of these TLRs and also identified differential functions of TLRs in activation of the inflammatory response. Collectively, we here demonstrate that S. pneumoniae, H. influenzae, and N. meningitidis each activate several TLRs in species-specific patterns and show that infection...

  5. Virulence evolution of the human pathogen Neisseria meningitidis by recombination in the core and accessory genome.

    Directory of Open Access Journals (Sweden)

    Biju Joseph

    Full Text Available BACKGROUND: Neisseria meningitidis is a naturally transformable, facultative pathogen colonizing the human nasopharynx. Here, we analyze on a genome-wide level the impact of recombination on gene-complement diversity and virulence evolution in N. meningitidis. We combined comparative genome hybridization using microarrays (mCGH and multilocus sequence typing (MLST of 29 meningococcal isolates with computational comparison of a subset of seven meningococcal genome sequences. PRINCIPAL FINDINGS: We found that lateral gene transfer of minimal mobile elements as well as prophages are major forces shaping meningococcal population structure. Extensive gene content comparison revealed novel associations of virulence with genetic elements besides the recently discovered meningococcal disease associated (MDA island. In particular, we identified an association of virulence with a recently described canonical genomic island termed IHT-E and a differential distribution of genes encoding RTX toxin- and two-partner secretion systems among hyperinvasive and non-hyperinvasive lineages. By computationally screening also the core genome for signs of recombination, we provided evidence that about 40% of the meningococcal core genes are affected by recombination primarily within metabolic genes as well as genes involved in DNA replication and repair. By comparison with the results of previous mCGH studies, our data indicated that genetic structuring as revealed by mCGH is stable over time and highly similar for isolates from different geographic origins. CONCLUSIONS: Recombination comprising lateral transfer of entire genes as well as homologous intragenic recombination has a profound impact on meningococcal population structure and genome composition. Our data support the hypothesis that meningococcal virulence is polygenic in nature and that differences in metabolism might contribute to virulence.

  6. Neisseria meningitidis ST11 Complex Isolates Associated with Nongonococcal Urethritis, Indiana, USA, 2015–2016

    Science.gov (United States)

    Toh, Evelyn; Gangaiah, Dharanesh; Batteiger, Byron E.; Williams, James A.; Arno, Janet N.; Tai, Albert; Batteiger, Teresa A.

    2017-01-01

    At a clinic in Indianapolis, Indiana, USA, we observed an increase in Neisseria gonorrhoeae–negative men with suspected gonococcal urethritis who had urethral cultures positive for N. meningitidis. We describe genomes of 2 of these N. meningitidis sequence type 11 complex urethritis isolates. Clinical evidence suggests these isolates may represent an emerging urethrotropic clade. PMID:28098538

  7. Neisseria meningitidis endocarditis: A case report and review of the literature.

    LENUS (Irish Health Repository)

    Ali, Mohammed

    2011-04-08

    Abstract Neisseria meningitidis is the leading cause of bacterial meningitis in children and young adults, with an overall mortality rate of up to 25%, but it is a rare cause of infective endocarditis. We present herein a case of N. meningitidis meningitis complicated with infective endocarditis.

  8. Neisseria meningitidis ST11 Complex Isolates Associated with Nongonococcal Urethritis, Indiana, USA, 2015-2016.

    Science.gov (United States)

    Toh, Evelyn; Gangaiah, Dharanesh; Batteiger, Byron E; Williams, James A; Arno, Janet N; Tai, Albert; Batteiger, Teresa A; Nelson, David E

    2017-02-01

    At a clinic in Indianapolis, Indiana, USA, we observed an increase in Neisseria gonorrhoeae-negative men with suspected gonococcal urethritis who had urethral cultures positive for N. meningitidis. We describe genomes of 2 of these N. meningitidis sequence type 11 complex urethritis isolates. Clinical evidence suggests these isolates may represent an emerging urethrotropic clade.

  9. Neisseria meningitidis Infecting a Prosthetic Knee Joint: A New Case of an Unusual Disease

    Directory of Open Access Journals (Sweden)

    Berta Becerril Carral

    2017-01-01

    Full Text Available Primary meningococcal meningitis is an infrequent but known disease. However, the infection of a prosthetic joint with Neisseria meningitidis is rare. We hereby describe the second case of an arthroplasty infected with Neisseria meningitidis that responded favourably to prosthesis retention with surgical debridement, in combination with antibiotics treatment.

  10. Neisseria meningitidis endocarditis: a case report and review of the literature.

    LENUS (Irish Health Repository)

    Ali, Mohammed

    2012-02-01

    Neisseria meningitidis is the leading cause of bacterial meningitis in children and young adults, with an overall mortality rate of up to 25%, but it is a rare cause of infective endocarditis. We present herein a case of N. meningitidis meningitis complicated with infective endocarditis.

  11. Ebf1 controls early cell differentiation in the embryonic striatum.

    Science.gov (United States)

    Garel, S; Marín, F; Grosschedl, R; Charnay, P

    1999-12-01

    Ebf1/Olf-1 belongs to a small multigene family encoding closely related helix-loop-helix transcription factors, which have been proposed to play a role in neuronal differentiation. Here we show that Ebf1 controls cell differentiation in the murine embryonic striatum, where it is the only gene of the family to be expressed. Ebf1 targeted disruption affects postmitotic cells that leave the subventricular zone (SVZ) en route to the mantle: they appear to be unable to downregulate genes normally restricted to the SVZ or to activate some mantle-specific genes. These downstream genes encode a variety of regulatory proteins including transcription factors and proteins involved in retinoid signalling as well as adhesion/guidance molecules. These early defects in the SVZ/mantle transition are followed by an increase in cell death, a dramatic reduction in size of the postnatal striatum and defects in navigation and fasciculation of thalamocortical fibres travelling through the striatum. Our data therefore show that Ebf1 plays an essential role in the acquisition of mantle cell molecular identity in the developing striatum and provide information on the genetic hierarchies that govern neuronal differentiation in the ventral telencephalon.

  12. 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

  13. 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

  14. Differential course of executive control changes during normal aging.

    Science.gov (United States)

    Treitz, Friederike H; Heyder, Katrin; Daum, Irene

    2007-07-01

    Normal aging has been associated with executive control deficits, but it is as yet unclear whether different executive subprocesses are differentially affected during the course of aging. The present study aimed to investigate age effects on a range of executive control subcomponents. Four consecutive age groups (20-30 years, 31-45 years, 46-60 years, 61-75 years), matched on present state IQ and mood, were compared on tasks of strategic memory processing, verbal fluency, reasoning, inhibition, task management, and self-rating of executive abilities. Deficits concerning the suppression of habitual and experimentally induced prepotent response tendencies and the ability to efficiently divide attention were observed in subjects over 60 years of age compared to the younger groups, while memory, verbal fluency, and reasoning were largely unaffected. Results suggest a sharp decline of executive function after age 60 and a differential course of different executive subcomponents across aging, adding further support to a multi-dimensional model of executive function.

  15. Genetic structure of Neisseria meningitidis serogroup C epidemic strains in South Brazil Estrutura genética de cepas epidêmicas de Neisseria meningitidis sorogrupo C do Sul do Brasil

    Directory of Open Access Journals (Sweden)

    Claudio Tavares Sacchi

    1995-08-01

    Full Text Available In the present study we report the results of an analysis, based on serotyping, multilocus enzyme electrophoresis (MEE, and ribotyping of N. meningitidis serogroup C strains isolated from patients with meningococcal disease (MD in Rio Grande do Sul (RS and Santa Catarina (SC States, Brazil, as the Center of Epidemiology Control of Ministry of Health detected an increasing of MD cases due to this serogroup in the last two years (1992-1993. We have demonstrated that the MD due to N.meningitidis serogroup C strains in RS and SC States occurring in the last 4 years were caused mainly by one clone of strains (ET 40, with isolates indistinguishable by serogroup, serotype, subtype and even by ribotyping. One small number of cases that were not due to an ET 40 strains, represent closely related clones that probably are new lineages generated from the ET 40 clone referred as ET 11A complex. We have also analyzed N.meningitidis serogroup C strains isolated in the greater São Paulo in 1976 as representative of the first post epidemic year in that region. The ribotyping method, as well as MEE, could provide useful information about the clonal characteristics of those isolates and also of strains isolated in south Brazil. The strains from 1976 have more similarity with the actual endemic than epidemic strains, by the ribotyping, sulfonamide sensitivity, and MEE results. In conclusion, serotyping with monoclonal antibodies (C:2b:P1.3, MEE (ET 11 and ET 11A complex, and ribotyping by using ClaI restriction enzyme (Rb2, were useful to characterize these epidemic strains of N.meningitidis related to the increased incidence of MD in different States of south Brazil. It is mostly probable that these N.meningitidis serogroup C strains have poor or no genetic corelation with 1971-1975 epidemic serogroup C strains. The genetic similarity of members of the ET 11 and ET 11A complex were confirmed by the ribotyping method by using three restriction endonucleases

  16. Differential-Drive Mobile Robot Control Design based-on Linear Feedback Control Law

    Science.gov (United States)

    Nurmaini, Siti; Dewi, Kemala; Tutuko, Bambang

    2017-04-01

    This paper deals with the problem of how to control differential driven mobile robot with simple control law. When mobile robot moves from one position to another to achieve a position destination, it always produce some errors. Therefore, a mobile robot requires a certain control law to drive the robot’s movement to the position destination with a smallest possible error. In this paper, in order to reduce position error, a linear feedback control is proposed with pole placement approach to regulate the polynoms desired. The presented work leads to an improved understanding of differential-drive mobile robot (DDMR)-based kinematics equation, which will assist to design of suitable controllers for DDMR movement. The result show by using the linier feedback control method with pole placement approach the position error is reduced and fast convergence is achieved.

  17. Distribution of the type III DNA methyltransferases modA, modB and modD among Neisseria meningitidis genotypes: implications for gene regulation and virulence.

    Science.gov (United States)

    Tan, Aimee; Hill, Dorothea M C; Harrison, Odile B; Srikhanta, Yogitha N; Jennings, Michael P; Maiden, Martin C J; Seib, Kate L

    2016-02-12

    Neisseria meningitidis is a human-specific bacterium that varies in invasive potential. All meningococci are carried in the nasopharynx, and most genotypes are very infrequently associated with invasive meningococcal disease; however, those belonging to the 'hyperinvasive lineages' are more frequently associated with sepsis or meningitis. Genome content is highly conserved between carriage and disease isolates, and differential gene expression has been proposed as a major determinant of the hyperinvasive phenotype. Three phase variable DNA methyltransferases (ModA, ModB and ModD), which mediate epigenetic regulation of distinct phase variable regulons (phasevarions), have been identified in N. meningitidis. Each mod gene has distinct alleles, defined by their Mod DNA recognition domain, and these target and methylate different DNA sequences, thereby regulating distinct gene sets. Here 211 meningococcal carriage and >1,400 disease isolates were surveyed for the distribution of meningococcal mod alleles. While modA11-12 and modB1-2 were found in most isolates, rarer alleles (e.g., modA15, modB4, modD1-6) were specific to particular genotypes as defined by clonal complex. This suggests that phase variable Mod proteins may be associated with distinct phenotypes and hence invasive potential of N. meningitidis strains.

  18. A combined Haemophilus influenzae type B Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine is immunogenic and well-tolerated when coadministered with diphtheria, tetanus, acellular pertussis hepatitis B-inactivated poliovirus at 3, 5 and 11 months of age: results of an open, randomized, controlled study.

    Science.gov (United States)

    Vesikari, Timo; Forstén, Aino; Desole, Maria Guiseppina; Ferrera, Giuseppe; Caubet, Magalie; Mesaros, Narcisa; Boutriau, Dominique

    2013-05-01

    This study evaluated the immunogenicity, reactogenicity and safety of the combined Haemophilus influenzae type B Neisseria meningitidis serogroup C tetanus toxoid conjugate vaccine (Hib-MenC-TT) coadministered with diphtheria, tetanus, acellular pertussis hepatitis B-inactivated poliovirus (DTPa-HBV-IPV) as 2 primary and 1 booster doses at 3, 5 and 11 months of age. In this phase III open study (NCT00327184), 709 infants were randomized in 2 parallel groups (1:1) to receive either Hib-MenC-TT coadministered with DTPa-HBV-IPV or control vaccines (MenC-TT coadministered with DTPa-HBV-IPV/Hib). Serum bactericidal activity for MenC (rSBA-MenC) and antibody concentrations against polyribosylribitol phosphate from Hib (anti-PRP) and hepatitis B (anti-HBs) were measured at 1 month after dose 2, before booster and 1 month after booster dose. Solicited (local/general) and unsolicited symptoms were assessed up to 4 and 31 days, respectively, after each vaccination. Serious adverse events were recorded throughout the study. One month after dose 2, high percentages of infants in both groups had rSBA-MenC titers ≥ 8 (≥ 99.1%), anti-PRP concentrations ≥ 0.15 μg/mL (≥ 96.5%) and anti-HBs concentrations ≥ 10 mIU/mL (≥ 95.3%), which persisted up to the booster vaccination (≥ 94.5%, ≥ 86.1%, ≥ 94.2%) and increased again after the booster dose (100%, 100%, ≥ 99%). Exploratory analyses indicated that rSBA-MenC geometric mean titers were lower and anti-PRP geometric mean concentrations were higher in the infants vaccinated with Hib-MenC-TT compared with the control vaccines at all time points. The safety profiles of the coadministered vaccines were similar in both groups. The Hib-MenC-TT and DTPa-HBV-IPV vaccines are immunogenic with a clinically acceptable safety profile when coadministered as 2 primary doses during infancy and 1 booster dose at 11 months of age.

  19. 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

  20. Shifts in the Antibiotic Susceptibility, Serogroups, and Clonal Complexes of Neisseria meningitidis in Shanghai, China: A Time Trend Analysis of the Pre-Quinolone and Quinolone Eras.

    Directory of Open Access Journals (Sweden)

    Mingliang Chen

    2015-06-01

    Full Text Available Fluoroquinolones have been used broadly since the end of the 1980s and have been recommended for Neisseria meningitidis prophylaxis since 2005 in China. The aim of this study was to determine whether and how N. meningitidis antimicrobial susceptibility, serogroup prevalence, and clonal complex (CC prevalence shifted in association with the introduction and expanding use of quinolones in Shanghai, a region with a traditionally high incidence of invasive disease due to N. meningitidis.A total of 374 N. meningitidis isolates collected by the Shanghai Municipal Center for Disease Control and Prevention between 1965 and 2013 were studied. Shifts in the serogroups and CCs were observed, from predominantly serogroup A CC5 (84% in 1965-1973 to serogroup A CC1 (58% in 1974-1985, then to serogroup C or B CC4821 (62% in 2005-2013. The rates of ciprofloxacin nonsusceptibility in N. meningitidis disease isolates increased from 0% in 1965-1985 to 84% (31/37 in 2005-2013 (p < 0.001. Among the ciprofloxacin-nonsusceptible isolates, 87% (27/31 were assigned to either CC4821 (n = 20 or CC5 (n = 7. The two predominant ciprofloxacin-resistant clones were designated ChinaCC4821-R1-C/B and ChinaCC5-R14-A. The ChinaCC4821-R1-C/B clone acquired ciprofloxacin resistance by a point mutation, and was present in 52% (16/31 of the ciprofloxacin-nonsusceptible disease isolates. The ChinaCC5-R14-A clone acquired ciprofloxacin resistance by horizontal gene transfer, and was found in 23% (7/31 of the ciprofloxacin-nonsusceptible disease isolates. The ciprofloxacin nonsusceptibility rate was 47% (7/15 among isolates from asymptomatic carriers, and nonsusceptibility was associated with diverse multi-locus sequence typing profiles and pulsed-field gel electrophoresis patterns. As detected after 2005, ciprofloxacin-nonsusceptible strains were shared between some of the patients and their close contacts. A limitation of this study is that isolates from 1986-2004 were not available

  1. 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.

  2. 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

  3. Biological Functions of the Secretome of Neisseria meningitidis

    Directory of Open Access Journals (Sweden)

    Jan Tommassen

    2017-06-01

    Full Text Available Neisseria meningitidis is a Gram-negative bacterial pathogen that normally resides as a commensal in the human nasopharynx but occasionally causes disease with high mortality and morbidity. To interact with its environment, it transports many proteins across the outer membrane to the bacterial cell surface and into the extracellular medium for which it deploys the common and well-characterized autotransporter, two-partner and type I secretion mechanisms, as well as a recently discovered pathway for the surface exposure of lipoproteins. The surface-exposed and secreted proteins serve roles in host-pathogen interactions, including adhesion to host cells and extracellular matrix proteins, evasion of nutritional immunity imposed by iron-binding proteins of the host, prevention of complement activation, neutralization of antimicrobial peptides, degradation of immunoglobulins, and permeabilization of epithelial layers. Furthermore, they have roles in interbacterial interactions, including the formation and dispersal of biofilms and the suppression of the growth of bacteria competing for the same niche. Here, we will review the protein secretion systems of N. meningitidis and focus on the functions of the secreted proteins.

  4. Vaccination with Attenuated Neisseria meningitidis Strains Protects against Challenge with Live Meningococci

    OpenAIRE

    Li, Yanwen; Sun, Yao-hui; Ison, Cathy; Levine, Myron M.; Tang, Christoph M.

    2004-01-01

    Meningococcal disease is a life-threatening infection caused by Neisseria meningitidis. Currently, there are no vaccines to prevent infection with serogroup B N. meningitidis strains, the leading cause of meningococcal meningitis in Europe and North America. Here we describe the construction and characterization of two attenuated serogroup B N. meningitidis strains, YH102 (MC58Δsia ΔrfaF) and YH103 (MC58Δsia ΔmetH). Both strains are markedly attenuated in their capacity to cause bacteremia in...

  5. Identification and optimization of critical process parameters for the production of NOMV vaccine against Neisseria meningitidis

    NARCIS (Netherlands)

    Waterbeemd, van de B.; Streefland, M.; Keulen, van L.J.M.; IJssel, van den J.; Bakker-de Haan, A.M.C.; Eppink, M.H.M.; Pol, van der L.A.

    2012-01-01

    Outer membrane vesicles (OMV) are used as a vaccine against Neisseria meningitidis serogroup B and are traditionally produced with detergent-extraction to remove toxic lipopolysaccharide. Engineered strains with attenuated lipopolysaccharide allowed the use of native vesicles (NOMV) with improved

  6. Meropenem susceptibility of Neisseria meningitidis and Streptococcus pneumoniae from meningitis patients in The Netherlands

    NARCIS (Netherlands)

    van de Beek, D.; Hensen, E. F.; Spanjaard, L.; de Gans, J.; Enting, R. H.; Dankert, J.

    1997-01-01

    In-vitro susceptibility of 299 Neisseria meningitidis and 157 Streptococcus pneumoniae strains from meningitis patients in The Netherlands in 1993 and 1994 to meropenem was determined using the Etest. Susceptibility to penicillin, ceftriaxone, and chloramphenicol was also determined. Rifampicin

  7. Peptide Selectivity of the Proton-Coupled Oligopeptide Transporter from Neisseria meningitidis

    DEFF Research Database (Denmark)

    Sharma, Neha; Aduri, Nanda G; Iqbal, Anna

    2016-01-01

    Peptide transport in living organisms is facilitated by either primary transport, hydrolysis of ATP, or secondary transport, cotransport of protons. In this study, we focused on investigating the ligand specificity of the Neisseria meningitidis proton-coupled oligopeptide transporter (Nm...

  8. 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.

  9. Cognitive Control Deficits Differentiate Adolescent Suicide Ideators From Attempters.

    Science.gov (United States)

    Stewart, Jeremy G; Glenn, Catherine R; Esposito, Erika C; Cha, Christine B; Nock, Matthew K; Auerbach, Randy P

    2017-06-01

    Mental illness and suicidal ideation are among the strongest correlates of suicidal behaviors, but few adolescents with these risk factors make a suicide attempt. Therefore, it is critical to identify factors associated with the transition from suicide ideation to attempts. The present study tested whether deficits in cognitive control in the context of suicide-relevant stimuli (ie, suicide interference) reliably differentiated adolescent ideators and attempters. Adolescents (n = 99; 71 girls) aged 13-18 years (mean = 15.53, SD = 1.34) with recent suicide ideation (n = 60) or a recent suicide attempt (n = 39) were recruited from an acute residential treatment facility between August 2012 and December 2013. We measured interference to suicide-related, negative, and positive words using the Suicide Stroop Task (SST). When stimuli were analyzed separately, suicide attempters showed greater interference for suicide (t₉₇ = 2.04, P = .044, d = 0.41) and positive (t₉₇ = 2.63, P = .010, d = 0.53) stimuli compared to suicide ideators. An additional omnibus interference (suicide, negative, positive) x group (suicide ideator, suicide attempter) analysis of variance revealed a main effect of group (F₁,₉₇ = 4.31, P = .041, ηp² = 0.04) but no interaction (P = .166), indicating that attempters showed greater interference for emotional stimuli, regardless of valence. Multiple attempters drove this effect; single attempters and ideators did not differ in SST performance (P = .608). General deficits in cognitive control in the context of emotional stimuli may be a marker of adolescent suicide risk. © Copyright 2017 Physicians Postgraduate Press, Inc.

  10. A generic mechanism in Neisseria meningitidis for enhanced resistance against bactericidal antibodies

    OpenAIRE

    Uria, Maria Jose; Zhang, Qian; Li, Yanwen; Chan, Angel; Exley, Rachel M.; Gollan, Bridget; Chan, Hannah; Feavers, Ian; Yarwood, Andy; Abad, Raquel; Borrow, Ray; Fleck, Roland A.; Mulloy, Barbara; Vazquez, Julio A.; Tang, Christoph M.

    2008-01-01

    The presence of serum bactericidal antibodies is a proven correlate of protection against systemic infection with the important human pathogen Neisseria meningitidis. We have identified three serogroup C N. meningitidis (MenC) isolates recovered from patients with invasive meningococcal disease that resist killing by bactericidal antibodies induced by the MenC conjugate vaccine. None of the patients had received the vaccine, which has been successfully introduced in countries in North America...

  11. Epidemiological markers in Neisseria meningitidis: an estimate of the performance of genotyping vs phenotyping

    DEFF Research Database (Denmark)

    Weis, N; Lind, I

    1998-01-01

    In order to estimate the performance of genotypic vs phenotypic characterization of Neisseria meningitidis, 2 methods, DNA fingerprinting and multilocus enzyme electrophoresis (MEE), were assessed as regards applicability, reproducibility and discriminating capacity. 50 serogroup B and 52 serogroup...... C Neisseria meningitidis strains from 96 patients with meningococcal disease and 22 serogroup C strains from healthy carriers were investigated. Both methods were 100% applicable to meningococcal strains and results of DNA fingerprinting as well as of MEE were reproducible. The number of types...

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

    African Journals Online (AJOL)

    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 model was ...

  13. The development of an experimental multiple serogroups vaccine for Neisseria meningitidis.

    Science.gov (United States)

    Pinto, Valerian B; Burden, Robert; Wagner, Allyn; Moran, Elizabeth E; Lee, Che-Hung

    2013-01-01

    A native outer membrane vesicles (NOMV) vaccine was developed from three antigenically diverse strains of Neisseria meningitidis that express the L1,8, L2, and L3,7 lipooligosaccharide (LOS) immunotypes, and whose synX, and lpxL1 genes were deleted.. Immunogenicity studies in mice showed that the vaccine induced bactericidal antibody against serogroups B, C, W, Y and X N. meningitidis strains. However, this experimental NOMV vaccine was not effective against serogroup A N. meningitidis strains. N. meningitidis capsular polysaccharide (PS) from serogroups A, C, W and Y were effective at inducing bactericidal antibody when conjugated to either tetanus toxoid or the fHbp1-fHbp2 fusion protein fHbp(1+2). The combination of the NOMV vaccine and the N. meningitidis serogroup A capsular polysaccharide (MAPS) protein conjugate was capable of inducing bactericidal antibodies against a limited number of N. meningitidis strains from serogroups A, B, C, W, Y and X tested in this study.

  14. 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 ...

  15. Sistema de Lotes de Siembra de cepas de Neisseria meningitidis cultivadas en medios de origen no animal

    Directory of Open Access Journals (Sweden)

    Carmen Alina del Puerto-Sardiñas

    2016-04-01

    Full Text Available En la producción de biológicos, especialmente aquellos obtenidos de microorganismos, resulta esencial contar con un suministro de cepas estable y bien caracterizado como materia prima para la producción. Para esto, es imprescindible conservar las cepas vacunales empleando el Sistema de Lotes de Siembra, así como contar con medios de cultivo que garanticen un óptimo crecimiento microbiano y la presencia de los antígenos de interés. En el Instituto Finlay de La Habana se trabaja en la obtención de una vacuna contra Neisseria meningitidis libre de componentes de origen animal. En el presente trabajo se elaboraron y caracterizaron Lotes de Siembra de Referencia y Trabajo de Neisseria meningitidis serogrupos A, C, Y, W135 y X cultivados en medios de origen no animal y cumpliendo con las Buenas Prácticas de Producción vigentes. Se estableció la documentación adecuada que incluye: expedientes de cada lote, los procedimientos normalizados de operación, los registros de elaboración y control de los lotes, las especificaciones de calidad y los certificados de ensayo.

  16. 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.

  17. 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

  18. Controllability of fractional order integro-differential inclusions with infinite delay

    Directory of Open Access Journals (Sweden)

    Khalida Aissani

    2014-11-01

    Full Text Available This paper concerns for controllability of fractional order integro-differential inclusions with infinite delay in Banach spaces. A theorem about the existence of mild solutions to the controllability of fractional order integro-differential inclusions is obtained based on Dhage fixed point theorem. An example is given to illustrate the existence result.

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

    OpenAIRE

    Chen, Xin; Zhang, Changhua; Huang, Qi; Ofori-Oduro, Mark

    2016-01-01

    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 ei...

  20. Multiplex quantitative PCR for detection of lower respiratory tract infection and meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis.

    Science.gov (United States)

    Abdeldaim, Guma M K; Strålin, Kristoffer; Korsgaard, Jens; Blomberg, Jonas; Welinder-Olsson, Christina; Herrmann, Björn

    2010-12-03

    Streptococcus pneumoniae and Haemophilus influenzae cause pneumonia and as Neisseria meningitidis they are important agents of meningitis. Although several PCR methods have been described for these bacteria the specificity is an underestimated problem. Here we present a quantitative multiplex real-time PCR (qmPCR) for detection of S. pneumoniae (9802 gene fragment), H. influenzae (omp P6 gene) and N. meningitidis (ctrA gene). The method was evaluated on bronchoalveolar lavage (BAL) samples from 156 adults with lower respiratory tract infection (LRTI) and 31 controls, and on 87 cerebrospinal fluid (CSF) samples from meningitis patients. The analytical sensitivity was not affected by using a combined mixture of reagents and a combined DNA standard (S. pneumoniae/H. influenzae/N. meningitidis) in single tubes. By blood- and BAL-culture and S. pneumoniae urinary antigen test, S. pneumoniae and H. influenzae were aetiological agents in 21 and 31 of the LTRI patients, respectively. These pathogens were identified by qmPCR in 52 and 72 of the cases, respectively, yielding sensitivities and specificities of 95% and 75% for S. pneumoniae, and 90% and 65% for H. influenzae, respectively. When using a cut-off of 10⁵ genome copies/mL for clinical positivity the sensitivities and specificities were 90% and 80% for S. pneumoniae, and 81% and 85% for H. influenzae, respectively. Of 44 culture negative but qmPCR positive for H. influenzae, 41 were confirmed by fucK PCR as H. influenzae. Of the 103 patients who had taken antibiotics prior to sampling, S. pneumoniae and H. influenzae were identified by culture in 6% and 20% of the cases, respectively, and by the qmPCR in 36% and 53% of the cases, respectively.In 87 CSF samples S. pneumoniae and N. meningitidis were identified by culture and/or 16 S rRNA in 14 and 10 samples and by qmPCR in 14 and 10 samples, respectively, giving a sensitivity of 100% and a specificity of 100% for both bacteria. The PCR provides increased

  1. Multiplex quantitative PCR for detection of lower respiratory tract infection and meningitis caused by Streptococcus pneumoniae, Haemophilus influenzae and Neisseria meningitidis

    Directory of Open Access Journals (Sweden)

    Welinder-Olsson Christina

    2010-12-01

    Full Text Available Abstract Background Streptococcus pneumoniae and Haemophilus influenzae cause pneumonia and as Neisseria meningitidis they are important agents of meningitis. Although several PCR methods have been described for these bacteria the specificity is an underestimated problem. Here we present a quantitative multiplex real-time PCR (qmPCR for detection of S. pneumoniae (9802 gene fragment, H. influenzae (omp P6 gene and N. meningitidis (ctrA gene. The method was evaluated on bronchoalveolar lavage (BAL samples from 156 adults with lower respiratory tract infection (LRTI and 31 controls, and on 87 cerebrospinal fluid (CSF samples from meningitis patients. Results The analytical sensitivity was not affected by using a combined mixture of reagents and a combined DNA standard (S. pneumoniae/H. influenzae/N. meningitidis in single tubes. By blood- and BAL-culture and S. pneumoniae urinary antigen test, S. pneumoniae and H. influenzae were aetiological agents in 21 and 31 of the LTRI patients, respectively. These pathogens were identified by qmPCR in 52 and 72 of the cases, respectively, yielding sensitivities and specificities of 95% and 75% for S. pneumoniae, and 90% and 65% for H. influenzae, respectively. When using a cut-off of 105 genome copies/mL for clinical positivity the sensitivities and specificities were 90% and 80% for S. pneumoniae, and 81% and 85% for H. influenzae, respectively. Of 44 culture negative but qmPCR positive for H. influenzae, 41 were confirmed by fucK PCR as H. influenzae. Of the 103 patients who had taken antibiotics prior to sampling, S. pneumoniae and H. influenzae were identified by culture in 6% and 20% of the cases, respectively, and by the qmPCR in 36% and 53% of the cases, respectively. In 87 CSF samples S. pneumoniae and N. meningitidis were identified by culture and/or 16 S rRNA in 14 and 10 samples and by qmPCR in 14 and 10 samples, respectively, giving a sensitivity of 100% and a specificity of 100% for both

  2. Retro - Prospective Differential Inclusions andtheir Control by the Differential Connection Tensors of their Evolutions: the Trendometer

    OpenAIRE

    Aubin, Jean-Pierre; Luxi, Chen; Dordan, Olivier

    2014-01-01

    24 pages; International audience; This study is motivated by two different, yet, connected, motivations. The first one follows the observation that the classical definition of derivatives involves prospective (or forward) difference quotients, not known whenever the time is directed, at least at the macroscopic level. Actually, the available and known derivatives are retrospective (or backward). They coïncide whenever the functions are differentiable in the classical sense, but not in the cas...

  3. Molecular Control of Interdigital Cell Death and Cell Differentiation by Retinoic Acid during Digit Development

    Directory of Open Access Journals (Sweden)

    Martha Elena Díaz-Hernández

    2014-04-01

    Full Text Available The precise coordination of cell death and cell differentiation during the formation of developing digits is essential for generating properly shaped limbs. Retinoic acid (RA has a fundamental role in digit development; it promotes or inhibits the molecular expression of several critical genes. This control of gene expression establishes molecular cascades that enable both the commencement of cell death and the inhibition of cell differentiation. In this review, we focus on the antagonistic functions between RA and fibroblast growth factor (FGF signaling in the control of cell death and between RA and transforming growth factor beta (TGFβ signaling in the control of cell differentiation.

  4. 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...

  5. Antimicrobial drug susceptibility of Neisseria meningitidis strains isolated from carriers

    Directory of Open Access Journals (Sweden)

    Dayamí García

    2000-06-01

    Full Text Available When it is necessary to determine the susceptibility of Neisseria meningitidis (Nm strains to antimicrobial drugs, it is important to consider that it should be analyzed in a double context. One of them related to the use of drugs in a specific medical treatment; and the other; to chemoprophylatic drugs, both with the same purpose: the accurate selection of the “in vivo” antimicrobial agent. This requires the study of the sensitivity and resistance of strains isolated in both carriers and patients. With the aim of further studying the behavior of the strains that currently circulate in Cuba, an antimicrobial drug susceptibility study was conducted in 90 strains isolated from carriers during the first half of 1998. The agar dilution method was used to determine the minimum inhibitory concentrations (MICs to: penicillin, ampicillin, rifampin, sulfadiazine, chloramphenicol, ciprofloxacin, ceftriaxone, cefotaxime. The study of the three latter drugs was done for the first time in our country. The search for β- lactamase-producer strains was also performed. There was a predominance of penicillin sensitive strains (82,2% with an intermediate sensitivity to ampicillin (57,8%, while 70% of the strains were sensitive to sulfadiazine. Regarding the rest of the antimicrobial drugs, 100% of the strains were sensitive. The paper shows the MICs for each drug as well as the phenotypic characteristics of the strains with the penicillin and sulfadiazine sensitivity and resistance patterns. No β-lactamase-producer strains were found.

  6. [Neisseria meningitidis urethritis: Two case reports].

    Science.gov (United States)

    Dubois, C; Liegeon, A-L; Fabbro, C; Truchetet, F

    2017-10-01

    Neisseria meningitidis (NM) is a commensal bacteria present in the oropharyngeal flora that causes invasive infections. There have been rarer reports of presence in the genital region. Herein, we present two cases of acute NM urethritis. Two men aged 30 and 31years, one of whom is homosexual and seropositive for HIV infection, presented urethral discharge which was diagnosed as acute urethritis. The unit through samples indicated the presence of NM of serogroups B and C. One of the antibiotic sensitivity tests revealed intermediate susceptibility to penicillin G and to amoxicillin. The clinical presentation of acute NM urethritis is non-specific, because of which urethral samples should be taken wherever acute urethritis is suspected. NM urethritis is infrequent and primarily affects men who have sex with men (MSM). Its current increase is due to unprotected oral-genital sexual practices. Due to the emergence of resistance to NM, antibiotic susceptibility testing should be carried out routinely to ensure appropriate therapy and prophylaxis. Cases of invasive serogroup C meningococcal infections have been recorded within the MSM population with hypothetical sexual port of entry. Thus, the French High Public Health Authority recommends vaccination against meningitis C in this population. Copyright © 2017. Published by Elsevier Masson SAS.

  7. [Carriers of Neisseria meningitidis among children from a primary school].

    Science.gov (United States)

    Martínez, Isabel; López, Omar; Sotolongo, Franklin; Mirabal, Mayelin; Bencomo, Antonio

    2003-01-01

    A cross-sectional and descriptive study was conducted among 318 children from the "Mártires del Corynthia" Primary School under the authorization of the Municipal Division of Education and the informed consent of their parents aimed at knowing the prevalence of meningoccoco carriers in school children, determining the epidemiological markers of the isolated strains and establishing the possible relation existing between the carrier and variables, such as age, sex, acute respiratory infection history, hacinamiento, amigdalectomy, inhibitory effect of of the accompanying flora and the secretory state of ABH antigens in saliva. All of them underwent nasopharyngeal exudate and a saliva sample was taken. In adition, the paents were surveyed about the risks factors to be investigated. 6.9 % of meningoccoco carriers were found and the NA:NT:P1:NST:L3,7,9 strains predominated. The risk factors with statistically significant results regarding the condition of carrier Neisseria meningitidis carrier were age, acute respiratory infection history, and the presence of Streptococcus pneumoniae and Neisseria lactamica of the accompanying bacterial flora in the nasopharynx of the children under study.

  8. Control of Differentiation of Human Mesenchymal Stem Cells by Altering the Geometry of Nanofibers

    Directory of Open Access Journals (Sweden)

    Satoshi Fujita

    2012-01-01

    Full Text Available Effective differentiation of mesenchymal stem cells (MSCs is required for clinical applications. To control MSC differentiation, induction media containing different types of soluble factors have been used to date; however, it remains challenging to obtain a uniformly differentiated population of an appropriate quality for clinical application by this approach. We attempted to develop nanofiber scaffolds for effective MSC differentiation by mimicking anisotropy of the extracellular matrix structure, to assess whether differentiation of these cells can be controlled by using geometrically different scaffolds. We evaluated MSC differentiation on aligned and random nanofibers, fabricated by electrospinning. We found that induction of MSCs into adipocytes was markedly more inhibited on random nanofibers than on aligned nanofibers. In addition, adipoinduction on aligned nanofibers was also inhibited in the presence of mixed adipoinduction and osteoinduction medium, although osteoinduction was not affected by a change in scaffold geometry. Thus, we have achieved localized control over the direction of differentiation through changes in the alignment of the scaffold even in the presence of a mixed medium. These findings indicate that precise control of MSC differentiation can be attained by using scaffolds with different geometry, rather than by the conventional use of soluble factors in the medium.

  9. 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

  10. [Postoperative pulmonary disease associated with haemophilus influenzae and neisseria meningitidis in a diabetic child].

    Science.gov (United States)

    Chemsi, Hicham; Frikh, Mohamed; Lemnouer, Abdelhay; Belfkih, Bouchra; Sekhsokh, Yassine; Chadli, Maryama; Elouennass, Mustapha

    2016-01-01

    Haemophilus influenzae is a saprophyte that colonizes the nasopharynx in nearly two thirds of children and adults. Neisseria meningitidis is a strict human bacterium which lives in the nasopharynx. It can cause benign nasopharyngitis or asymptomatic colonization. We report the case of a diabetic child with postoperative pneumonia associated with Haemophilus influenzae and Neisseria meningitidis. A 3-year old diabetic patient admitted to the Department of Cardiac Surgery due to delayed surgical treatment. The postoperative course was marked by a worsening of respiratory status caused by abundant secretions requiring patient admission to the intensive care unit. An assessment for the detection of infections was performed, including protected distal sampling which revealed the association of Neisseria meningitidis with Haemophilus influenzae. This case study allowed us to highlight bacterial associations in certain high-risk situations. Each of these two species is responsible for various infections. However their presence in the same infected site is rare.

  11. [Real-time PCR detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae DNA in clinical specimens].

    Science.gov (United States)

    Vacková, Z; Lžičařová, D; Stock, N K; Kozáková, J

    2015-10-01

    The study aim was to implement a molecular real-time polymerase chain reaction (PCR) assay recommended by the CDC (Centers for Disease Control and Prevention) for the detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae in clinical (culture negative) specimens from patients with suspected invasive bacterial disease. Clinical specimens are referred to the National Reference Laboratory (NRL) for Meningococcal Infections, Unit for Airborne Bacterial Infections, Centre for Epidemiology and Microbiology, National Institute of Public Health from various regions of the Czech Republic. Clinical specimens are, in particular, cerebrospinal fluid, anti-coagulated blood or serum and, exceptionally, post-mortem specimens. The NRL has implemented molecular diagnosis of these bacterial pathogens involved in meningitis and sepsis from clinical specimens since 1999. The first diagnostic method was semi-nested PCR followed by electrophoretic analysis. In 2014, a molecular qualitative real-time PCR assay was implemented.

  12. 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.

  13. 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...... given by the electronic differential based on throttle and steering angle is decomposed into frequency components. Numerical simulation results are provided for both wavelet and proportional-integral-derivate controllers. In comparison, the proposed wavelet control technique provides greater stability...... and ensures smooth control of the two back driving wheels....

  14. 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...

  15. Controlled Osteogenic Differentiation of Mouse Mesenchymal Stem Cells by Tetracycline-Controlled Transcriptional Activation of Amelogenin.

    Directory of Open Access Journals (Sweden)

    Fangfang Wang

    Full Text Available Regenerative dental therapies for bone tissues rely on efficient targeting of endogenous and transplanted mesenchymal stem cells (MSCs to guide bone formation. Amelogenin is the primary component of Emdogain, which is used to regenerate periodontal defects; however, the mechanisms underlying the therapeutic effects on alveolar bone remain unclear. The tetracycline (Tet-dependent transcriptional regulatory system is a good candidate to investigate distinct roles of genes of interest during stem cell differentiation. Here, we investigated amelogenin-dependent regulation of osteogenesis in MSCs by establishing a Tet-controlled transcriptional activation system. Clonal mouse bone marrow-derived MSCs were lentivirally transduced with the Tet repressor (TetR expression vector followed by drug selection to obtain MSCs constitutively expressing TetR (MSCs-TetR. Expression vectors that contained the Tet operator and amelogenin-coding (Amelx cDNA fragments were constructed using the Gateway system and lentivirally introduced into MSCs-TetR to generate a Tet regulation system in MSCs (MSCs-TetR/Amelx. MSCs-TetR/Amelx significantly overexpressed the Amelx gene and protein in the presence of the tetracycline derivative doxycycline. Concomitant expression of osterix, bone sialoprotein (BSP, osteopontin, and osteocalcin was modulated by addition or removal of doxycycline under osteogenic guidance. During osteogenic induction, MSCs-TetR/Amelx treated with doxycycline showed significantly increased gene expression of osterix, type I collagen, BSP, and osteocalcin in addition to increased alkaline phosphatase activity and mineralized nodule formation. Enhanced extracellular matrix calcification was observed when forced Amelx expression commenced at the early stage but not at the intermediate or late stages of osteogenesis. These results suggest that a Tet-controlled Amelx gene regulation system for mouse MSCs was successfully established, in which transcriptional

  16. Influence of the Length of the Lipooligosaccharide α Chain on Its Sialylation in Neisseria meningitidis

    OpenAIRE

    Tsai, Chao-Ming; Kao, George; Zhu, Peixuan

    2002-01-01

    The sialylation of lipooligosaccharide (LOS) in Neisseria meningitidis plays a role in the resistance of the organism to killing by normal human serum. The length of the α chain extending out from the heptose I [Hep (I)] moiety of LOS influenced sialylation of N. meningitidis LOS in vitro and in vivo. The α chain required a terminal Gal and a trisaccharide or longer oligosaccharide to serve as an acceptor for sialylation. The disaccharide lactose (Galβ1-4Glc) in the α chain of immunotype L8 L...

  17. Combined Admission Control and Scheduling for QoS Differentiation in LTE Uplink

    DEFF Research Database (Denmark)

    Anas, Mohmmad; Rosa, Claudio; Calabrese, Francesco Davide

    2008-01-01

    Long term evolution (LTE) architecture shall support end-to-end quality of service (QoS). For the QoS support and service differentiation it is important that the admission control and packet scheduling functionalities are QoS-aware. In this paper a combined admission control and a decoupled time......-frequency domain scheduling framework for LTE uplink is presented. The proposed framework is shown to effectively differentiate QoS user classes in a mixed traffic scenario....

  18. Numerical solutions of differential Riccati Equations Arising in Optimal Control Problems for Parabolic Partial Differential Equations

    OpenAIRE

    Mena Pazmiño, Hermann Segundo

    2007-01-01

    152 hojas : ilustraciones, 29 x 21 cm + CD-ROM 0859 Las ecuaciones diferenciales de Riccati (DREs) aparecen en muchas aplicaciones de ciencia e ingeniería, en especial en la teoría de control. Problemas de optimización gobernados por ecuaciones diferenciales parciales (EDPs) con frecuencia pueden formularse como problemas de Cauchy abstractos si además se impone un funcional de costo cuadrático se obtiene un problema linear quadratic regulador (LQR) para un sistema de dimensión infinita. L...

  19. Genomic Epidemiology of Hypervirulent Serogroup W, ST-11 Neisseria meningitidis.

    Science.gov (United States)

    Mustapha, Mustapha M; Marsh, Jane W; Krauland, Mary G; Fernandez, Jorge O; de Lemos, Ana Paula S; Dunning Hotopp, Julie C; Wang, Xin; Mayer, Leonard W; Lawrence, Jeffrey G; Hiller, N Luisa; Harrison, Lee H

    2015-10-01

    Neisseria meningitidis is a leading bacterial cause of sepsis and meningitis globally with dynamic strain distribution over time. Beginning with an epidemic among Hajj pilgrims in 2000, serogroup W (W) sequence type (ST) 11 emerged as a leading cause of epidemic meningitis in the African 'meningitis belt' and endemic cases in South America, Europe, Middle East and China. Previous genotyping studies were unable to reliably discriminate sporadic W ST-11 strains in circulation since 1970 from the Hajj outbreak strain (Hajj clone). It is also unclear what proportion of more recent W ST-11 disease clusters are caused by direct descendants of the Hajj clone. Whole genome sequences of 270 meningococcal strains isolated from patients with invasive meningococcal disease globally from 1970 to 2013 were compared using whole genome phylogenetic and major antigen-encoding gene sequence analyses. We found that all W ST-11 strains were descendants of an ancestral strain that had undergone unique capsular switching events. The Hajj clone and its descendants were distinct from other W ST-11 strains in that they shared a common antigen gene profile and had undergone recombination involving virulence genes encoding factor H binding protein, nitric oxide reductase, and nitrite reductase. These data demonstrate that recent acquisition of a distinct antigen-encoding gene profile and variations in meningococcal virulence genes was associated with the emergence of the Hajj clone. Importantly, W ST-11 strains unrelated to the Hajj outbreak contribute a significant proportion of W ST-11 cases globally. This study helps illuminate genomic factors associated with meningococcal strain emergence and evolution.

  20. Large Cluster of Neisseria meningitidis Urethritis in Columbus, Ohio, 2015.

    Science.gov (United States)

    Bazan, Jose A; Turner, Abigail Norris; Kirkcaldy, Robert D; Retchless, Adam C; Kretz, Cecilia B; Briere, Elizabeth; Tzeng, Yih-Ling; Stephens, David S; Maierhofer, Courtney; Del Rio, Carlos; Abrams, A Jeanine; Trees, David L; Ervin, Melissa; Licon, Denisse B; Fields, Karen S; Roberts, Mysheika Williams; Dennison, Amanda; Wang, Xin

    2017-07-01

    Neisseria meningitidis (Nm) is a Gram-negative diplococcus that normally colonizes the nasopharynx and rarely infects the urogenital tract. On Gram stain of urethral exudates, Nm can be misidentified as the more common sexually transmitted pathogen Neisseria gonorrhoeae. In response to a large increase in cases of Nm urethritis identified among men presenting for screening at a sexually transmitted disease clinic in Columbus, Ohio, we investigated the epidemiologic characteristics of men with Nm urethritis and the molecular and phylogenetic characteristics of their Nm isolates. The study was conducted between 1 January and 18 November 2015. Seventy-five Nm urethritis cases were confirmed by biochemical and polymerase chain reaction testing. Men with Nm urethritis were a median age of 31 years (interquartile range [IQR] = 24-38) and had a median of 2 sex partners in the last 3 months (IQR = 1-3). Nm cases were predominantly black (81%) and heterosexual (99%). Most had urethral discharge (91%), reported oral sex with a female in the last 12 months (96%), and were treated with a ceftriaxone-based regimen (95%). A minority (15%) also had urethral chlamydia coinfection. All urethral Nm isolates were nongroupable, ST-11 clonal complex (cc11), ET-15, and clustered together phylogenetically. Urethral Nm isolates were similar by fine typing (PorA P1.5-1,10-8, PorB 2-2, FetA F3-6), except 2, which had different PorB types (2-78 and 2-52). Between January and November 2015, 75 urethritis cases due to a distinct Nm clade occurred among primarily black, heterosexual men in Columbus, Ohio. Future urogenital Nm infection studies should focus on pathogenesis and modes of sexual transmission. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  1. Genomic Epidemiology of Hypervirulent Serogroup W, ST-11 Neisseria meningitidis

    Science.gov (United States)

    Mustapha, Mustapha M.; Marsh, Jane W.; Krauland, Mary G.; Fernandez, Jorge O.; de Lemos, Ana Paula S.; Dunning Hotopp, Julie C.; Wang, Xin; Mayer, Leonard W.; Lawrence, Jeffrey G.; Hiller, N. Luisa; Harrison, Lee H.

    2015-01-01

    Neisseria meningitidis is a leading bacterial cause of sepsis and meningitis globally with dynamic strain distribution over time. Beginning with an epidemic among Hajj pilgrims in 2000, serogroup W (W) sequence type (ST) 11 emerged as a leading cause of epidemic meningitis in the African ‘meningitis belt’ and endemic cases in South America, Europe, Middle East and China. Previous genotyping studies were unable to reliably discriminate sporadic W ST-11 strains in circulation since 1970 from the Hajj outbreak strain (Hajj clone). It is also unclear what proportion of more recent W ST-11 disease clusters are caused by direct descendants of the Hajj clone. Whole genome sequences of 270 meningococcal strains isolated from patients with invasive meningococcal disease globally from 1970 to 2013 were compared using whole genome phylogenetic and major antigen-encoding gene sequence analyses. We found that all W ST-11 strains were descendants of an ancestral strain that had undergone unique capsular switching events. The Hajj clone and its descendants were distinct from other W ST-11 strains in that they shared a common antigen gene profile and had undergone recombination involving virulence genes encoding factor H binding protein, nitric oxide reductase, and nitrite reductase. These data demonstrate that recent acquisition of a distinct antigen-encoding gene profile and variations in meningococcal virulence genes was associated with the emergence of the Hajj clone. Importantly, W ST-11 strains unrelated to the Hajj outbreak contribute a significant proportion of W ST-11 cases globally. This study helps illuminate genomic factors associated with meningococcal strain emergence and evolution. PMID:26629539

  2. 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.

  3. Efficient differential evolution algorithms for multimodal optmal control problems

    NARCIS (Netherlands)

    Lopez Cruz, I.L.; Willigenburg, van L.G.; Straten, van G.

    2003-01-01

    Many methods for solving optimal control problems, whether direct or indirect, rely upon gradient information and therefore may converge to a local optimum. Global optimisation methods like Evolutionary algorithms, overcome this problem. In this work it is investigated how well novel and easy to

  4. 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

  5. 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.

  6. Survivors of septic shock caused by Neisseria meningitidis in childhood : Psychosocial outcomes in young adulthood

    NARCIS (Netherlands)

    Vermunt, Lindy C.; Buysse, Corinne M.; Joosten, Koen F.; Duivenvoorden, Hugo J.; Hazelzet, Jan A.; Verhulst, Frank C.; Utens, Elisabeth M.

    2011-01-01

    Objective: To investigate long-term psychosocial outcomes in young adults who survived septic shock caused by Neisseria meningitidis (meningococcal septic shock) during childhood. Design: A cross-sectional study. Setting: The psychological investigation took place in the department of Child and

  7. Towards an improved Neisseria meningitidis B vaccine: vesicular PorA formulations

    NARCIS (Netherlands)

    Arigita Maza, C. (Carmen)

    2003-01-01

    There is a great need for vaccines against Neisseria meningitidis serogroup B. This is especially important in Western European countries, were approximately two thirds of the cases of meningococcal disease can be attributed to serogroup B strains. Against this serogroup, traditional vaccines based

  8. Comparison of commercial diagnostic tests for identification of serogroup antigens of Neisseria meningitidis

    NARCIS (Netherlands)

    van der Ende, A.; Schuurman, I. G.; Hopman, C. T.; Fijen, C. A.; Dankert, J.

    1995-01-01

    In the study that is described the sensitivities and specificities of three commercial tests and the standard Reference Laboratory test, used since 1961, to identify Neisseria meningitidis serogroups were compared. The tests marketed by Difco, Murex/Wellcome, and Sanofi/Pasteur showed overall

  9. NMR resonance assignments of NarE, a putative ADP-ribosylating toxin from Neisseria meningitidis

    NARCIS (Netherlands)

    Carlier, L.P.A.; Köhler, Christian; Veggi, D.; Pizza, M.; Soriani, M.; Boelens, R.; Bonvin, A.M.J.J.

    2011-01-01

    NarE is a 16 kDa protein identified from Neisseria meningitidis, one of the bacterial pathogens responsible for meningitis. NarE belongs to the ADP-ribosyltransferase family and catalyses the transfer of ADP-ribose moieties to arginine residues in target protein acceptors. Many pathogenic bacteria

  10. A dual role of extracellular DNA during biofilm formation of Neisseria meningitidis

    DEFF Research Database (Denmark)

    Lappann, M.; Claus, H.; van Alen, T.

    2010-01-01

    -acetylmuramyl-l-alanine amidase genes. In late biofilms, outer membrane phospholipase A-dependent autolysis, which was observed in most cc, but not in ST-8 and ST-11 strains, was required for shear force resistance of microcolonies. Taken together, N. meningitidis evolved two different biofilm formation strategies, an e...

  11. Genome sequence of Neisseria meningitidis serogroup B strain H44/76

    NARCIS (Netherlands)

    Piet, J. R.; Huis in 't Veld, R. A. G.; van Schaik, B. D. C.; van Kampen, A. H. C.; Baas, F.; van de Beek, D.; Pannekoek, Y.; van der Ende, A.

    2011-01-01

    Neisseria meningitidis is an obligate human pathogen. While it is a frequent commensal of the upper respiratory tract, in some individuals the bacterium spreads to the bloodstream, causing meningitis and/or sepsis, which are serious conditions with high morbidity and mortality. Here we report the

  12. Olfactory nerve--a novel invasion route of Neisseria meningitidis to reach the meninges.

    Directory of Open Access Journals (Sweden)

    Hong Sjölinder

    Full Text Available Neisseria meningitidis is a human-specific pathogen with capacity to cause septic shock and meningitis. It has been hypothesized that invasion of the central nervous system (CNS is a complication of a bacteremic condition. In this study, we aimed to characterize the invasion route of N. meningitidis to the CNS. Using an intranasally challenged mouse disease model, we found that twenty percent of the mice developed lethal meningitis even though no bacteria could be detected in blood. Upon bacterial infection, epithelial lesions and redistribution of intracellular junction protein N-cadherin were observed at the nasal epithelial mucosa, especially at the olfactory epithelium, which is functionally and anatomically connected to the CNS. Bacteria were detected in the submucosa of the olfactory epithelium, along olfactory nerves in the cribriform plate, at the olfactory bulb and subsequently at the meninges and subarachnoid space. Furthermore, our data suggest that a threshold level of bacteremia is required for the development of meningococcal sepsis. Taken together, N. meningitidis is able to pass directly from nasopharynx to meninges through the olfactory nerve system. This study enhances our understanding how N. meningitidis invades the meninges. The nasal olfactory nerve system may be a novel target for disease prevention that can improve outcome and survival.

  13. Fit genotypes and escape variants of subgroup III Neisseria meningitidis during three pandemics of epidemic meningitis

    NARCIS (Netherlands)

    Zhu, P.; van der Ende, A.; Falush, D.; Brieske, N.; Morelli, G.; Linz, B.; Popovic, T.; Schuurman, I. G.; Adegbola, R. A.; Zurth, K.; Gagneux, S.; Platonov, A. E.; Riou, J. Y.; Caugant, D. A.; Nicolas, P.; Achtman, M.

    2001-01-01

    The genetic variability at six polymorphic loci was examined within a global collection of 502 isolates of subgroup III, serogroup A Neisseria meningitidis. Nine "genoclouds" were identified, consisting of genotypes that were isolated repeatedly plus 48 descendent genotypes that were isolated

  14. Celulitis por Neisseria meningitidis: comunicación de un caso

    OpenAIRE

    Lissarrague, Sabina; Bernstein, Judith Celina; Schell, Celia María; Stagnaro, J. P.; De Luca, María Marta; López, M.; Basualdo Farjat, Juan Ángel; Sparo, Mónica

    2017-01-01

    Objetivo: comunicar un caso de celulitis por Neisseria meningitidis en muslo izquierdo en un lactante atendido en el Hospital de Niños del Municipio de Tandil, Provincia de Buenos Aires e investigar la portación familiar de esta bacteria.

  15. Survivors of septic shock caused by Neisseria meningitidis in childhood: psychosocial outcomes in young adulthood

    NARCIS (Netherlands)

    Vermunt, Lindy C.; Buysse, Corinne M.; Joosten, Koen F.; Duivenvoorden, Hugo J.; Hazelzet, Jan A.; Verhulst, Frank C.; Utens, Elisabeth M.

    2011-01-01

    To investigate long-term psychosocial outcomes in young adults who survived septic shock caused by Neisseria meningitidis (meningococcal septic shock) during childhood. A cross-sectional study. The psychological investigation took place in the department of Child and Adolescent Psychiatry of the

  16. The iron-regulated transcriptome and proteome of Neisseria meningitidis serogroup C

    Czech Academy of Sciences Publication Activity Database

    Basler, Marek; Linhartová, Irena; Halada, Petr; Novotná, Jana; Bezoušková, Silvia; Osička, Radim; Weiser, Jaroslav; Vohradský, Jiří; Šebo, Peter

    2006-01-01

    Roč. 6, č. 23 (2006), s. 6194-6206 ISSN 1615-9853 R&D Projects: GA ČR GA310/04/0804; GA MZe 1G46068 Institutional research plan: CEZ:AV0Z50200510 Keywords : iron regulation * Neisseria meningitidis * proteome Subject RIV: EE - Microbiology, Virology Impact factor: 5.735, year: 2006

  17. A unified active damping control for single-phase differential buck inverter with LCL-filter

    DEFF Research Database (Denmark)

    Yao, Wenli; Wang, Xiongfei; Zhang, Xiaobin

    2015-01-01

    and control of a grid-connected differential mode buck inverter with an LCL filter. A generalized small-signal model of the inverter is built first with the averaged switching model. It is shown that the LCL filter resonance merely occurs in the differential mode, while an LC filter resonance exists......The single-phase differential mode buck inverter is recently introduced with a differential mode for power transfer and a common mode for actively decoupling the second-order power oscillation. However, it is limited to islanded applications with an LC filter. This paper addresses the stability...... in the common mode, provided that the filter parameters of the two bridges are kept the same. A unified active damping control approach is then proposed for stabilizing the inverter and improving the transient performance under a wide range of grid impedance. Lastly, experimental tests are carried out...

  18. 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.

  19. Standardization of Neisseria meningitidis Serogroup B Colorimetric Serum Bactericida Assay

    Science.gov (United States)

    Rodríguez, Tamara; Lastre, Miriam; Cedré, Barbara; Campo, Judith del; Bracho, Gustavo; Zayas, Caridad; Taboada, Carlos; Díaz, Miriam; Sierra, Gustavo; Pérez, Oliver

    2002-01-01

    The correlate of protection for serogroup B meningococci is not currently known, but for serogroup C it is believed to be the serum bactericidal assay (SBA). The current SBAs are labor intensive and the variations in protocols among different laboratories make interpretation of results difficult. A colorimetric SBA (cSBA), based on the ability of Neisseria meningitidis serogroup B to consume glucose, leading to acid production, was standardized by using group B strain Cu385-83 as the target. The cSBA results were compared to those obtained for a traditional colony-counting microassay (mSBA). Glucose and bromocresol purple pH indicator were added to the medium in order to estimate growth of cSBA target cell survivors through color change. Different variants of the assay parameters were optimized: growth of target cells (Mueller Hinton agar plates), target cell number (100 CFU/per well), and human complement source used at a final concentration of 25%. After the optimization, three other group B strains (H44/76, 490/91, and 511/91) were used as targets for the cSBA. The selection of the assay parameters and the standardization of cSBA were done with 13 sera from vaccinated volunteers. The titers were determined as the higher serum dilution that totally inhibited the bacterial growth marked by the color invariability of the pH indicator. This was detected visually as well as spectrophotometrically and was closely related to a significant difference in the growth of target cell survivors determined using Student’s t test. Intralaboratory reproducibility was ±1 dilution. The correlation between bactericidal median titers and specific immunoglobulin G serum concentration by enzyme immunoassay was high (r = 0.910, P < 0.01). The bactericidal titers generated by the cSBA and the mSBA were nearly identical, and there was a high correlation between the two assays (r = 0.974, P < 0.01). The standardized cSBA allows easy, fast, and efficient evaluation of samples. PMID

  20. Detection of Neisseria meningitidis in a paediatric patient with septic arthritis using multiplexed diagnostic PCR targeting meningitis/encephalitis (ME).

    LENUS (Irish Health Repository)

    O'Sullivan, Donnchadh

    2018-03-23

    Neisseria meningitidis is associated with meningitis and septicemia. Septic meningococcal arthritis is relatively uncommon and its diagnosis associated with clinical and microbiological challenges. Early recognition and treatment is required to prevent joint destruction.

  1. Mechanisms of dexamethasone-mediated inhibition of Toll-like receptor signaling induced by Neisseria meningitidis and Streptococcus pneumoniae

    DEFF Research Database (Denmark)

    Mogensen, Trine; Berg, Randi S; Paludan, Søren R

    2008-01-01

    significantly reduces mortality and morbidity from bacterial meningitis. Here we investigate the molecular mechanisms behind the inhibitory effect of dexamethasone upon the inflammatory responses evoked by Neisseria meningitidis and Streptococcus pneumoniae, two of the major causes of bacterial meningitis......B alpha synthesis. Our data also revealed that the timing of steroid treatment relative to infection was important for achieving strong inhibition, particularly in response to S. pneumoniae. Altogether, we describe important targets of dexamethasone in the inflammatory responses evoked by N. meningitidis...

  2. 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.

  3. 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.

  4. Two-dimensional material-based bionano platforms to control mesenchymal stem cell differentiation.

    Science.gov (United States)

    Kang, Ee-Seul; Kim, Da-Seul; Suhito, Intan Rosalina; Lee, Wanhee; Song, Inbeom; Kim, Tae-Hyung

    2018-01-01

    In the past decade, stem cells, with their ability to differentiate into various types of cells, have been proven to be resourceful in regenerative medicine and tissue engineering. Despite the ability to repair damaged parts of organs and tissues, the use of stem cells still entails several limitations, such as low differentiation efficiency and difficulties in guiding differentiation. To address these limitations, nanotechnology approaches have been recently implemented in stem cell research. It has been discovered that stem cells, in combination with carbon-based functional materials, show enhanced regenerative performances in varying biophysical conditions. In particular, several studies have reported solutions to the conventional quandaries in biomedical engineering, using synergetic effects of nanohybrid materials, as well as further development of technologies to recover from diverse health conditions such as bone fracture and strokes. In this review, we discuss several prior studies regarding the application of various nanomaterials in controlling the behavior of stem cells. We focus on the potential of different types of nanomaterials, such as two-dimensional materials, gold nanoparticles, and three-dimensional nanohybrid composites, to control the differentiation of human mesenchymal stem cells (hMSCs). These materials have been found to affect stem cell functions via the adsorption of growth/differentiation factors on the surfaces of nanomaterials and the activation of signaling pathways that are mostly related to cell adhesion and differentiation (e.g., FAK, Smad, Erk, and Wnt). Controlling stem cell differentiation using biophysical factors, especially the use of nanohybrid materials to functionalize underlying substrates wherein the cells attach and grow, is a promising strategy to achieve cells of interest in a highly efficient manner. We hope that this review will facilitate the use of other types of newly discovered and/or synthesized nanomaterials

  5. The Control of Mesenchymal Stromal Cell Osteogenic Differentiation through Modified Surfaces

    Directory of Open Access Journals (Sweden)

    Niall Logan

    2013-01-01

    Full Text Available Stem cells continue to receive widespread attention due to their potential to revolutionise treatments in the fields of both tissue engineering and regenerative medicine. Adult stem cells, specifically mesenchymal stromal cells (MSCs, play a vital role in the natural events surrounding bone healing and osseointegration through being stimulated to differentiate along their osteogenic lineage and in doing so, they form new cortical and trabecular bone tissue. Understanding how to control, manipulate, and enhance the intrinsic healing events modulated through osteogenic differentiation of MSCs by the use of modified surfaces and biomaterials could potentially advance the fields of both orthopaedics and dentistry. This could be by either using surface modification to generate greater implant stability and more rapid healing following implantation or the stimulation of MSCs ex vivo for reimplantation. This review aims to gather publications targeted at promoting, enhancing, and controlling the osteogenic differentiation of MSCs through biomaterials, nanotopographies, and modified surfaces for use in implant procedures.

  6. 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.

  7. 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.

  8. 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.

  9. Controllability of impulsive functional differential systems with infinite delay in Banach spaces

    International Nuclear Information System (INIS)

    Chang Yongkui

    2007-01-01

    The paper establishes a sufficient condition for the controllability of the first-order impulsive functional differential systems with infinite delay in Banach spaces. We use Schauder's fixed point theorem combined with a strongly continuous operator semigroup. An example is given to illustrate our results

  10. 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.

  11. 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.

  12. 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....

  13. Surface modifications by gas plasma control osteogenic differentiation of MC3T3-E1 cells

    NARCIS (Netherlands)

    Barradas, A.M.C.; Lachmann, K.; Hlawacek, G.; Frielink, C.; Truckenmüller, R.K.; Boerman, O.C.; van Gastel, Raoul; Garritsen, H.S.P.; Garritsen, H.S.P.; Thomas, M.; Moroni, Lorenzo; van Blitterswijk, Clemens; de Boer, Jan

    2012-01-01

    Numerous studies have shown that the physicochemical properties of biomaterials can control cell activity. Cell adhesion, proliferation, differentiation as well as tissue formation in vivo can be tuned by properties such as the porosity, surface micro- and nanoscale topography and chemical

  14. Surface modifications by gas plasma control osteogenic differentiation of MC3T3-E1 cells.

    NARCIS (Netherlands)

    Barradas, A.M.; Lachmann, K.; Hlawacek, G.; Frielink, C.; Truckenmoller, R.; Boerman, O.C.; Gastel, R. van; Garritsen, H.; Thomas, M.; Moroni, L.; Blitterswijk, C. Van; Boer, J. den

    2012-01-01

    Numerous studies have shown that the physicochemical properties of biomaterials can control cell activity. Cell adhesion, proliferation, differentiation as well as tissue formation in vivo can be tuned by properties such as the porosity, surface micro- and nanoscale topography and chemical

  15. Primary cilia control hedgehog signaling during muscle differentiation and are deregulated in rhabdomyosarcoma

    Science.gov (United States)

    Fu, Wenxiang; Asp, Patrik; Canter, Brian; Dynlacht, Brian David

    2014-01-01

    The primary cilium acts as a cellular antenna, transducing diverse signaling pathways, and recent evidence suggests that primary cilia are important in development and cancer. However, a role for cilia in normal muscle development and rhabdomyosarcoma (RMS) has not been explored. Here we implicate primary cilia in proliferation, hedgehog (Hh) signaling, and differentiation of skeletal muscle cells. Cilia and Hh signaling are highly dynamic during the differentiation of myoblasts. We show that cilia are assembled during the initial stages of myogenic differentiation but disappear as cells progress through myogenesis, concomitant with the destruction of proteins critical for cilia assembly and shortly after the Hh effector, Gli3, leaves the cilium. Importantly, we show that ablation of primary cilia strongly suppresses Hh signaling and myogenic differentiation while enhancing proliferation. Interestingly, our data further indicate that both cilia assembly and Hh signaling are deregulated in RMS, and cilia respond to Hh ligand in certain subsets of RMS cells but not others. Together, these findings provide evidence for an essential role for both primary cilia assembly and disassembly in the control of Hh signaling and early differentiation in muscle cells. We suggest that the temporally orchestrated destruction of centrosomal and ciliary proteins is a necessary antecedent for removal of the primary cilium and cessation of Hh signaling during myogenic differentiation. Additionally, our results further stratify RMS populations and highlight cilia assembly and disassembly as potential RMS drug targets. PMID:24927541

  16. 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.

  17. On the use of stochastic differential geometry for non-equilibrium thermodynamic modeling and control

    Science.gov (United States)

    Muratore-Ginanneschi, Paolo

    2013-07-01

    We discuss the relevance of geometric concepts in the theory of stochastic differential equations for applications to the theory of non-equilibrium thermodynamics of small systems. In particular, we show how the Eells-Elworthy-Malliavin covariant construction of the Wiener process on a Riemann manifold provides a physically transparent formulation of optimal control problems of finite-time thermodynamic transitions. Based on this formulation, we turn to an evaluative discussion of recent results on optimal thermodynamic control and their interpretation.

  18. Nonzero-Sum Stochastic Differential Game between Controller and Stopper for Jump Diffusions

    Directory of Open Access Journals (Sweden)

    Yan Wang

    2013-01-01

    Full Text Available We consider a nonzero-sum stochastic differential game which involves two players, a controller and a stopper. The controller chooses a control process, and the stopper selects the stopping rule which halts the game. This game is studied in a jump diffusions setting within Markov control limit. By a dynamic programming approach, we give a verification theorem in terms of variational inequality-Hamilton-Jacobi-Bellman (VIHJB equations for the solutions of the game. Furthermore, we apply the verification theorem to characterize Nash equilibrium of the game in a specific example.

  19. 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.

  20. 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.

  1. Epidemiological markers in Neisseria meningitidis: an estimate of the performance of genotyping vs phenotyping

    DEFF Research Database (Denmark)

    Weis, N; Lind, I

    1998-01-01

    In order to estimate the performance of genotypic vs phenotypic characterization of Neisseria meningitidis, 2 methods, DNA fingerprinting and multilocus enzyme electrophoresis (MEE), were assessed as regards applicability, reproducibility and discriminating capacity. 50 serogroup B and 52 serogroup...... C Neisseria meningitidis strains from 96 patients with meningococcal disease and 22 serogroup C strains from healthy carriers were investigated. Both methods were 100% applicable to meningococcal strains and results of DNA fingerprinting as well as of MEE were reproducible. The number of types...... defined by DNA fingerprinting and MEE as compared to that defined by phenotypic characteristics (serogroup, serotype, serosubtype and sulphonamide resistance) was as follows: for serogroup B strains from patients, 11 and 12 vs 8; for serogroup C strains from patients, 10 and 15 vs 8; and for serogroup C...

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

    DEFF Research Database (Denmark)

    Wu, Xunwei; Quondamatteo, Fabio; Lefever, Tine

    2006-01-01

    Differentiation of skin stem cells into hair follicles (HFs) requires the inhibition of beta-catenin degradation, which is controlled by a complex containing axin and the protein kinase GSK3beta. Using conditional gene targeting in mice, we show now that the small GTPase Cdc42 is crucial...... 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...... progenitor cells in vivo....

  3. Zinc piracy as a mechanism of Neisseria meningitidis for evasion of nutritional immunity.

    Science.gov (United States)

    Stork, Michiel; Grijpstra, Jan; Bos, Martine P; Mañas Torres, Carmen; Devos, Nathalie; Poolman, Jan T; Chazin, Walter J; Tommassen, Jan

    2013-10-01

    The outer membrane of Gram-negative bacteria functions as a permeability barrier that protects these bacteria against harmful compounds in the environment. Most nutrients pass the outer membrane by passive diffusion via pore-forming proteins known as porins. However, diffusion can only satisfy the growth requirements if the extracellular concentration of the nutrients is high. In the vertebrate host, the sequestration of essential nutrient metals is an important defense mechanism that limits the growth of invading pathogens, a process known as "nutritional immunity." The acquisition of scarce nutrients from the environment is mediated by receptors in the outer membrane in an energy-requiring process. Most characterized receptors are involved in the acquisition of iron. In this study, we characterized a hitherto unknown receptor from Neisseria meningitidis, a causative agent of sepsis and meningitis. Expression of this receptor, designated CbpA, is induced when the bacteria are grown under zinc limitation. We demonstrate that CbpA functions as a receptor for calprotectin, a protein that is massively produced by neutrophils and other cells and that has been shown to limit bacterial growth by chelating Zn²⁺ and Mn²⁺ ions. Expression of CbpA enables N. meningitidis to survive and propagate in the presence of calprotectin and to use calprotectin as a zinc source. Besides CbpA, also the TonB protein, which couples energy of the proton gradient across the inner membrane to receptor-mediated transport across the outer membrane, is required for the process. CbpA was found to be expressed in all N. meningitidis strains examined, consistent with a vital role for the protein when the bacteria reside in the host. Together, our results demonstrate that N. meningitidis is able to subvert an important defense mechanism of the human host and to utilize calprotectin to promote its growth.

  4. Zinc piracy as a mechanism of Neisseria meningitidis for evasion of nutritional immunity.

    Directory of Open Access Journals (Sweden)

    Michiel Stork

    2013-10-01

    Full Text Available The outer membrane of Gram-negative bacteria functions as a permeability barrier that protects these bacteria against harmful compounds in the environment. Most nutrients pass the outer membrane by passive diffusion via pore-forming proteins known as porins. However, diffusion can only satisfy the growth requirements if the extracellular concentration of the nutrients is high. In the vertebrate host, the sequestration of essential nutrient metals is an important defense mechanism that limits the growth of invading pathogens, a process known as "nutritional immunity." The acquisition of scarce nutrients from the environment is mediated by receptors in the outer membrane in an energy-requiring process. Most characterized receptors are involved in the acquisition of iron. In this study, we characterized a hitherto unknown receptor from Neisseria meningitidis, a causative agent of sepsis and meningitis. Expression of this receptor, designated CbpA, is induced when the bacteria are grown under zinc limitation. We demonstrate that CbpA functions as a receptor for calprotectin, a protein that is massively produced by neutrophils and other cells and that has been shown to limit bacterial growth by chelating Zn²⁺ and Mn²⁺ ions. Expression of CbpA enables N. meningitidis to survive and propagate in the presence of calprotectin and to use calprotectin as a zinc source. Besides CbpA, also the TonB protein, which couples energy of the proton gradient across the inner membrane to receptor-mediated transport across the outer membrane, is required for the process. CbpA was found to be expressed in all N. meningitidis strains examined, consistent with a vital role for the protein when the bacteria reside in the host. Together, our results demonstrate that N. meningitidis is able to subvert an important defense mechanism of the human host and to utilize calprotectin to promote its growth.

  5. Resurgence of Neisseria meningitidis serogroup W ST-11 (cc11) in Madagascar, 2015-2016.

    Science.gov (United States)

    Rasoanandrasana, Saïda; Raberahona, Mihaja; Milenkov, Milen; Rakotomahefa Narison, Mbolanirina Lala; Ranaivo Rabetokotany, Felana; Rakotovao, Luc; Randria, Mamy Jean de Dieu; Hong, Eva; Paranhos-Baccalà, Glaucia; Taha, Muhamed-Kheir; Rakoto-Andrianarivelo, Mala

    2017-02-01

    The resurgence of invasive meningococcal disease caused by Neisseria meningitidis serogroup W with sequence type ST-11 (cc11) was observed in Madagascar in 2015-2016. Three cases were investigated in this study. Molecular characterization of the strains suggests the local transmission of a single genotype that may have been circulating for years. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  6. The Neisseria meningitidis Outer Membrane Lipoprotein FrpD Binds the RTX Protein FrpC

    Czech Academy of Sciences Publication Activity Database

    Procházková, Kateřina; Osička, Radim; Linhartová, Irena; Halada, Petr; Šulc, Miroslav; Šebo, Peter

    2005-01-01

    Roč. 280, č. 5 (2005), s. 3251-3258 ISSN 0021-9258 R&D Projects: GA ČR GA310/02/1448 Grant - others:Howard Hughes Medical Institute International Research Scholarship Award 55000334 Institutional research plan: CEZ:AV0Z50200510 Keywords : neisseria meningitidis * FrpD * FrpC Subject RIV: EE - Microbiology, Virology Impact factor: 5.854, year: 2005

  7. Crystallographic characterization of the outer membrane lipoprotein FrpD from Neisseria meningitidis

    Czech Academy of Sciences Publication Activity Database

    Sviridova, Ekaterina; Bumba, Ladislav; Řezáčová, Pavlína; Veverka, Václav; Šebo, Peter; Kutá-Smatanová, Ivana

    2015-01-01

    Roč. 22, č. 1 (2015), s. 57-58 ISSN 1211-5894. [Discussions in Structural Molecular Biology. Annual Meeting of the Czech Society for Structural Biology /13./. 19.03.2015-21.03.2015, Nové Hrady] R&D Projects: GA ČR(CZ) GAP207/11/0717; GA MŠk(CZ) LC06010 Institutional support: RVO:61388963 ; RVO:67179843 ; RVO:61388971 Keywords : FrpD * Neisseria meningitidis Subject RIV: CE - Biochemistry

  8. Backbone resonance assignments of the outer membrane lipoprotein FrpD from Neisseria meningitidis

    Czech Academy of Sciences Publication Activity Database

    Bumba, Ladislav; Sviridova, E.; Kutá-Smatanová, Ivana; Řezáčová, Pavlína; Veverka, Václav

    2014-01-01

    Roč. 8, č. 1 (2014), s. 53-55 ISSN 1874-2718 R&D Projects: GA ČR(CZ) GAP207/11/0717; GA MŠk(CZ) LK11205 Institutional support: RVO:61388963 ; RVO:61388971 ; RVO:67179843 Keywords : Neisseria meningitidis * FrpC * FrpD * backbone assignments * NMR * iron-regulated protein Subject RIV: CE - Biochemistry Impact factor: 0.760, year: 2014

  9. Structural characterization of the lipid A component of pathogenic Neisseria meningitidis.

    OpenAIRE

    Kulshin, V A; Zähringer, U; Lindner, B; Frasch, C E; Tsai, C M; Dmitriev, B A; Rietschel, E T

    1992-01-01

    The lipid A component of meningococcal lipopolysaccharide was structurally characterized by using chemical modification methods, methylation analysis, 31P nuclear magnetic resonance, and laser desorption mass spectroscopy. It was shown that Neisseria meningitidis lipid A consists of a 1,4'-bisphosphorylated beta(1'----6)-linked D-glucosamine disaccharide (lipid A backbone), both phosphate groups being largely replaced by O-phosphorylethanolamine. This disaccharide harbors two nonsubstituted h...

  10. Prevalence of Neisseria meningitidis carriage: a small-scale survey in Istanbul, Turkey.

    Science.gov (United States)

    Kepenekli Kadayifci, Eda; Güneşer Merdan, Deniz; Soysal, Ahmet; Karaaslan, Ayşe; Atıcı, Serkan; Durmaz, Rıza; Boran, Perran; Turan, İhsan; Söyletir, Güner; Bakır, Mustafa

    2016-04-28

    The human nasopharynx is the main reservoir of Neisseria meningitidis, and asymptomatic carriage is common. N. meningitidis one of the common causes of bacterial meningitis in Turkey, especially after the implementation of the national immunization program that includes conjugated pneumococcal and Haemophilus influenzae type b vaccines. The purpose of this study was to evaluate the prevalence of meningococcal carriage and determine the leading serogroup, which may help authorities to adapt appropriate meningococal vaccine into the national immunization programme. The prevalence of oropharyngeal carriage of N. meningitidis in 1,000 healthy subjects, 0-79 years of age, was investigated. Oropharyngeal swabs were collected during an 18-month period. Samples obtained were inoculated onto Thayer-Martin agar. The API-NH test and VITEK-MS system were used for identification of colonies. Multiplex real-time polymerase chain reaction assay was used to determine serogroups with serogroup-specific genes. N. meningitidis was isolated from 6 of 1,000 subjects (0.6%). Meningoccocal carriers were between 21 and 40 years of age. All isolates were serogrouped as B, except one that did not survive on subculture. N. lactamica was isolated from 13 of 1,000 subjects (1.3%). Carriage rate of meningococci in our study was relatively low. However, we detected that serogroup B was the leading strain in meningococcal carriage in Istanbul; choosing an appropriate meningococcal vaccine containing serogroup B should therefore be considered. High absolute humidity throughout the year in Istanbul may explain the low prevalence of carriage in our study. This should be verified with a multicenter national survey.

  11. 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.

  12. Analysis of the Bactericidal Response to an Experimental Neisseria meningitidis Vesicle Vaccine

    Science.gov (United States)

    Moran, Elizabeth E.; Burden, Robert; Labrie, Joseph E.; Wen, Zhiyun; Wang, Xin-Min; Zollinger, Wendell D.; Zhang, Lan

    2012-01-01

    Rabbit immunogenicity studies on an experimental trivalent native outer membrane vesicle vaccine derived from three serogroup B strains were conducted to evaluate the effectiveness of this vaccine at inducing an antibody response with serum bactericidal activity against meningococcal strains of other serogroups in addition to serogroup B strains. The results showed that the vaccine was capable of inducing an effective broad-based bactericidal antibody response in rabbits against a small sample of Neisseria meningitidis strains of serogroups C, W135, and X and, to a lesser extent, serogroups A and Y. Analysis of antibody specificity using a bactericidal depletion assay revealed that antibodies to lipooligosaccharide (LOS), PorA, and NadA induced in rabbits by the experimental trivalent outer membrane vesicle vaccine were responsible for most of the bactericidal activity against strains of the other N. meningitidis serogroups. In the case of serogroup A N. meningitidis strains, the outer membrane antigen NadA was primarily responsible for protection. The outer membrane antigens fHbp and OpcA were also effective in removing some bactericidal activity from the sera. PMID:22461527

  13. Structural and Biochemical Characterization of the Oxidoreductase NmDsbA3 from Neisseria meningitidis

    Energy Technology Data Exchange (ETDEWEB)

    Vivian, Julian P.; Scoullar, Jessica; Robertson, Amy L.; Bottomley, Stephen P.; Horne, James; Chin, Yanni; Wielens, Jerome; Thompson, Philip E.; Velkov, Tony; Piek, Susannah; Byres, Emma; Beddoe, Travis; Wilce, Matthew C.J.; Kahler, Charlene M.; Rossjohn, Jamie; Scanlon, Martin J. (UWA); (Monash)

    2009-09-02

    DsbA is an enzyme found in the periplasm of Gram-negative bacteria that catalyzes the formation of disulfide bonds in a diverse array of protein substrates, many of which are involved in bacterial pathogenesis. Although most bacteria possess only a single essential DsbA, Neisseria meningitidis is unusual in that it possesses three DsbAs, although the reason for this additional redundancy is unclear. Two of these N. meningitidis enzymes (NmDsbA1 and NmDsbA2) play an important role in meningococcal attachment to human epithelial cells, whereas NmDsbA3 is considered to have a narrow substrate repertoire. To begin to address the role of DsbAs in the pathogenesis of N. meningitidis, we have determined the structure of NmDsbA3 to 2.3-{angstrom} resolution. Although the sequence identity between NmDsbA3 and other DsbAs is low, the NmDsbA3 structure adopted a DsbA-like fold. Consistent with this finding, we demonstrated that NmDsbA3 acts as a thiol-disulfide oxidoreductase in vitro and is reoxidized by Escherichia coli DsbB (EcDsbB). However, pronounced differences in the structures between DsbA3 and EcDsbA, which are clustered around the active site of the enzyme, suggested a structural basis for the unusual substrate specificity that is observed for NmDsbA3.

  14. Nasopharyngeal Carriage Rate and Serogroups of Neisseria meningitidis in Turkish recruits upon entry to the military

    Directory of Open Access Journals (Sweden)

    Ahmet Basustaoglu

    2011-08-01

    Full Text Available Aim: The aim of this study was to determine nasopharyngeal carriage rate and serogroup of Neisseria meningitidis strains isolated from Turkish recruits upon entry to the military. Material and Methods: Nasopharyngeal swab samples were obtained from 1995 soldiers and were inoculated immediately on BBL-modified Thayer-Martin medium plates. The plates were examined for the presence of colonies showing the typical morphology of N. meningitidis. Suspect colonies were screened for oxidase reactivity, and positive colonies were Gram stained. If Gram-negative diplococci were present, a biochemical profile by the API NH system was used for confirmation. Serogrouping of the meningococcal isolates was performed by a slide agglutination technique. Findings: The nasopharyngeal carriage rate of N. meningitidis was found to be 4.2% (n=83. Of these meningococci, 15.6% (n=13 were serogroup Y, 10.8% (n=9 were serogroup W-135, 9.6% (n=8 were serogroup C, 6.1% (n=5 were serogroup B, 2.4% (n=2 were serogroup A. The 46 isolates (55.4% were detected as nonserogroupable. Conclusion: Since serogroup Y and W-135 are predominant in this study population, it was suggest that Turkish recruits should be vaccinated by quadrivalent vaccine (A,C,Y, and W-135 upon the military instead of A+C polysaccharide vaccine and now quadrivalent vaccine has been carried out. [TAF Prev Med Bull 2011; 10(4.000: 447-450

  15. 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.

  16. 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.

  17. 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.

  18. Comparison of PCR-based methods for the simultaneous detection of Neisseria meningitidis, Haemophilus influenzae, and Streptococcus pneumoniae in clinical samples.

    Science.gov (United States)

    de Filippis, Ivano; de Andrade, Claudia Ferreira; Caldeira, Nathalia; de Azevedo, Aline Carvalho; de Almeida, Antonio Eugenio

    2016-01-01

    Several in-house PCR-based assays have been described for the detection of bacterial meningitis caused by Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae from clinical samples. PCR-based methods targeting different bacterial genes are frequently used by different laboratories worldwide, but no standard method has ever been established. The aim of our study was to compare different in-house and a commercial PCR-based tests for the detection of bacterial pathogens causing meningitis and invasive disease in humans. A total of 110 isolates and 134 clinical samples (99 cerebrospinal fluid and 35 blood samples) collected from suspected cases of invasive disease were analyzed. Specific sets of primers frequently used for PCR-diagnosis of the three pathogens were used and compared with the results achieved using the multiplex approach described here. Several different gene targets were used for each microorganism, namely ctrA, crgA and nspA for N. meningitidis, ply for S. pneumoniae, P6 and bexA for H. influenzae. All used methods were fast, specific and sensitive, while some of the targets used for the in-house PCR assay detected lower concentrations of genomic DNA than the commercial method. An additional PCR reaction is described for the differentiation of capsulated and non-capsulated H. influenzae strains, the while commercial method only detects capsulated strains. The in-house PCR methods here compared showed to be rapid, sensitive, highly specific, and cheaper than commercial methods. The in-house PCR methods could be easily adopted by public laboratories of developing countries for diagnostic purposes. The best results were achieved using primers targeting the genes nspA, ply, and P6 which were able to detect the lowest DNA concentrations for each specific target. Copyright © 2016 Elsevier Editora Ltda. All rights reserved.

  19. Some Differential Inequalities on Time Scales and Their Applications to Feedback Control Systems

    Directory of Open Access Journals (Sweden)

    Yonghong Fan

    2017-01-01

    Full Text Available This paper deals with feedback control systems on time scales. Firstly, we generalize the semicycle concept to time scales and then establish some differential inequalities on time scales. Secondly, as applications of these inequalities, we study the uniform ultimate boundedness of solutions of these systems. We give a new method to investigate the permanence of ecosystem on time scales. And some known results have been generalized. Finally, an example is given to support the result.

  20. 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.

  1. 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.

  2. 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

  3. Multiple-locus variable-number tandem repeat analysis of Neisseria meningitidis yields groupings similar to those obtained by multilocus sequence typing.

    NARCIS (Netherlands)

    Schouls, Leo M; Ende, Arie van der; Damen, Marjolein; Pol, Ingrid van de

    2006-01-01

    We identified many variable-number tandem repeat (VNTR) loci in the genomes of Neisseria meningitidis serogroups A, B, and C and utilized a number of these loci to develop a multiple-locus variable-number tandem repeat analysis (MLVA). Eighty-five N. meningitidis serogroup B and C isolates obtained

  4. Description of an unusual Neisseria meningitidis isolate containing and expressing Neisseria gonorrhoeae-Specific 16S rRNA gene sequences.

    Science.gov (United States)

    Walcher, Marion; Skvoretz, Rhonda; Montgomery-Fullerton, Megan; Jonas, Vivian; Brentano, Steve

    2013-10-01

    An apparently rare Neisseria meningitidis isolate containing one copy of a Neisseria gonorrhoeae 16S rRNA gene is described herein. This isolate was identified as N. meningitidis by biochemical identification methods but generated a positive signal with Gen-Probe Aptima assays for the detection of Neisseria gonorrhoeae. Direct 16S rRNA gene sequencing of the purified isolate revealed mixed bases in signature regions that allow for discrimination between N. meningitidis and N. gonorrhoeae. The mixed bases were resolved by sequencing individually PCR-amplified single copies of the genomic 16S rRNA gene. A total of 121 discrete sequences were obtained; 92 (76%) were N. meningitidis sequences, and 29 (24%) were N. gonorrhoeae sequences. Based on the ratio of species-specific sequences, the N. meningitidis strain seems to have replaced one of its four intrinsic 16S rRNA genes with the gonococcal gene. Fluorescence in situ hybridization (FISH) probes specific for meningococcal and gonococcal rRNA were used to demonstrate the expression of the rRNA genes. Interestingly, the clinical isolate described here expresses both N. meningitidis and N. gonorrhoeae 16S rRNA genes, as shown by positive FISH signals with both probes. This explains why the probes for N. gonorrhoeae in the Gen-Probe Aptima assays cross-react with this N. meningitidis isolate. The N. meningitidis isolate described must have obtained N. gonorrhoeae-specific DNA through interspecies recombination.

  5. Gibberellin mediates daylength-controlled differentiation of vegetative meristems in strawberry (Fragaria x ananassa Duch).

    Science.gov (United States)

    Hytönen, Timo; Elomaa, Paula; Moritz, Thomas; Junttila, Olavi

    2009-02-11

    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 x 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. 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. 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 induction of cell division in subapical tissues of axillary

  6. 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

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

    Science.gov (United States)

    Hytönen, Timo; Elomaa, Paula; Moritz, Thomas; Junttila, Olavi

    2009-01-01

    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 induction of cell division in

  8. Adaptive lyapunov control and artificial neural networks for spacecraft relative maneuvering using atmospheric differential drag

    Science.gov (United States)

    Perez Chaparro, David Andres

    At low Earth orbits, a differential in the drag acceleration between spacecraft can be used to control their relative motion. This drag differential allows for a propellant-free alternative to thrusters for performing relative maneuvers in these orbits. The interest in autonomous propellant-less maneuvering comes from the desire to reduce the costs of spacecraft formations. Formation maneuvering opens up a wide variety of new applications for spacecraft missions, such as on-orbit maintenance and refueling. In this work atmospheric differential drag based nonlinear controllers are presented that can be used for virtually any planar relative maneuver of two spacecraft, provided that there is enough atmospheric density and that the spacecraft can change their ballistic coefficients by sufficient amounts to generate the necessary differential accelerations. The control techniques are successfully tested using high fidelity Satellite Tool Kit simulations for re-phase, fly-around, and rendezvous maneuvers, proving the feasibility of the proposed approach for a real flight. Furthermore, the atmospheric density varies in time and in space as the spacecraft travel along their orbits. The ability to accurately forecast the density allows for accurate onboard orbit propagation and for creating realistic guidance trajectories for maneuvers that rely on the differential drag. In this work a localized density predictor based on artificial neural networks is also presented. The predictor uses density measurements or estimates along the past orbits and can use a set of proxies for solar and geomagnetic activities to predict the value of the density along the future orbits of the spacecraft. The performance of the localized predictor is studied for different neural network structures, testing periods of high and low solar and geomagnetic activities and different prediction windows. Comparison with previously developed methods show substantial benefits in using neural networks, both

  9. 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.

  10. Discretized partial differential equations - Examples of control systems defined on modules

    Science.gov (United States)

    Brockett, R. W.; Willems, J. L.

    1974-01-01

    The purpose of this paper is to show how the important problems of linear system theory can be solved concisely for a particular class of linear systems, namely block circulant systems, by exploiting the algebraic structure. This type of system arises in lumped approximations to linear partial differential equations. The computation of the transition matrix, the variation of constants formula, observability, controllability, pole allocation, realization theory, stability and quadratic optimal control are discussed. In principle, all questions which are solved here could also be solved by standard methods; the present paper clearly exposes the structure of the solution, and thus permits various savings in computational effort.

  11. Randomised controlled trial on differential learning of toothbrushing in 6- to 9-year-old children.

    Science.gov (United States)

    Pabel, Sven-Olav; Freitag, Franziska; Hrasky, Valentina; Zapf, Antonia; Wiegand, Annette

    2018-03-09

    This study aimed to evaluate the effect of differential learning of toothbrushing compared to habitual toothbrushing and instruction/demonstration of toothbrushing on plaque reduction and gingival inflammation of primary school children. Children (6-9 years) were subjected to a toothbrushing training consisting of 15 days (3 × 5 days, interval 2 days, 3 min/day) and randomly assigned to one of three groups (each n = 18): habitual toothbrushing/control, instruction/demonstration of toothbrushing, differential learning of toothbrushing. The differential learning approach comprised 15 different movement exercises (1/day), while instruction/demonstration of toothbrushing was based on repetitive practice of toothbrushing. Plaque (Turesky-modified Quigley-Hein plaque index (T-QHI)) and papilla bleeding (papilla bleeding index (PBI)) scores were assessed prior to the first toothbrushing (t0, baseline) and 21 (t1), 42 (t2) and 63 (t3) days after beginning of the study. Primary statistical analyses were performed with cumulative logit regression models with repeated measures. The global significance level was set to 5% two-sided. At all time points, PBI and T-QHI were significantly reduced by differential learning compared to instruction/demonstration of toothbrushing and habitual toothbrushing. Compared to baseline, differential learning improved PBI and T-QHI significantly at all time points. In the other groups, no significant reduction of PBI compared to baseline was observed. T-QHI was significantly reduced by habitual toothbrushing only at t1 and by instruction/demonstration of toothbrushing at t1 and t2. Differential learning had an improved effect on posterior compared to anterior teeth. Differential learning of toothbrushing improved plaque reduction and reduced gingival inflammation compared to habitual toothbrushing and instruction/demonstration of toothbrushing in 6- to 9-year-old children in mixed dentition. Toothbrushing skills of children might

  12. 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.

  13. 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.

  14. In silico analysis of different generation β lactams antibiotics with penicillin binding protein-2 of Neisseria meningitidis for curing meningococcal disease.

    Science.gov (United States)

    Tripathi, Vijay; Tripathi, Pooja; Srivastava, Navita; Gupta, Dwijendra

    2014-12-01

    Neisseria meningitidis is a gram negative, diplococcic pathogen responsible for the meningococcal disease and fulminant septicemia. Penicillin-binding proteins-2 (PBPs) is crucial for the cell wall biosynthesis during cell proliferation of N. meningitidis and these are the target for β-lactam antibiotics. For many years penicillin has been recognized as the antibiotic for meningococcal disease but the meningococcus has seemed to be antibiotic resistance. In the present work we have verified the molecular interaction of Penicillin binding protein-2 N. meningitidis to different generation of β-lactam antibiotics and concluded that the third generation of β-lactam antibiotics shows efficient binding with Penicillin binding protein-2 of N. meningitidis. On the basis of binding efficiency and inhibition constant, ceftazidime emerged as the most efficient antibiotic amongst the other advanced β-lactam antibiotics against Penicillin-binding protein-2 of N. meningitidis.

  15. MenACWY-CRM, a novel quadrivalent glycoconjugate vaccine against Neisseria meningitidis for the prevention of meningococcal infection.

    Science.gov (United States)

    Pace, David

    2009-12-01

    Invasive meningococcal disease remains a major public health concern, with infants, children younger than 4 years and adolescents bearing the majority of the global disease burden. Protecting the vulnerable individuals in these age groups through vaccination remains the most rational strategy for the prevention of meningococcal disease. The formulation of polysaccharide-protein conjugate vaccines has been a major breakthrough in vaccinology, and has extended protection against pathogenic encapsulated bacteria to younger age groups. The dramatic decline in the incidence of Neisseria meningitidis serogroup C disease, observed following the introduction of glycoconjugate meningococcal C vaccines, demonstrates that vaccination can control disease at a population level. The development of quadrivalent glycoconjugate meningococcal ACWY vaccines has broadened protection against meningococcal disease. A novel meningococcal MenACWY-CRM (Menveo) glycoconjugate vaccine, formulated by selective conjugation chemistry of intermediate-chain-length meningococcal saccharides, was immunogenic in individuals aged 2 months to 65 years. The reactogenicity of MenACWY-CRM was similar to that of other licensed meningococcal glycoconjugates, yet the vaccine has the potential to extend protection against meningococcal serogroups A, Y and W-135 to children younger than 2 years of age - a need that remains unmet.

  16. Neonatal sepsis and meningitis caused by Neisseria meningitidis: a case report Sepse e meningite neonatal por Neisseria meningitidis: relato de caso

    Directory of Open Access Journals (Sweden)

    Mário Cícero Falcão

    2007-06-01

    Full Text Available OBJECTIVE: To report a full-term newborn infant that developed a sepsis associated to meningitis caused by Neisseria meningitidis serogroup C on the 14th day of life. CASE DESCRIPTION: The patient was a term female infant, born to a mother with Systemic Lupus Erythematosus, with birth weight of 2,610g, Apgar Score 1, 4 and 8, who needed mechanical ventilation for 24 hours. On the 7th day of life, the neonate was discharged from the hospital with good overall condition. On the 15th day of life, the newborn infant presented fever and respiratory failure. The cerebrospinal fluid showed 1042 cells/mm³, with neutrophilic predominance, protein of 435 mg/dL, and glucose OBJETIVO: Relatar o caso de um recém-nascido de termo que apresentou no 14º dia de vida sepse associada à meningite, cujo agente etiológico foi a Neisseria meningitidis sorotipo C. DESCRIÇÃO DO CASO: recém-nascido de termo, cuja mãe é portadora de lupus eritematoso sistêmico, feminino, peso de nascimento de 2610g, Escala de Apgar 1, 4 e 8, sendo intubado e ventilado por 24 horas. Recebeu alta no 7º dia de vida em boas condições. No 15º dia de vida apresentou febre e desconforto respiratório. O líquido cefalorraquidiano mostrou 1042 células/mm³, com predomínio de neutrófilos, proteinorraquia de 435 mg/dL e glicorraquia < 10 mg/dL; a bacterioscopia revelou a presença de diplococos. Foi internado na Terapia Intensiva Neonatal, necessitou de ventilação mecânica e de drogas vasoativas. A hemocultura e a cultura do líquido cefalorraquidiano foram positivas para Neisseria meningitidis C. O recém-nascido foi tratado por 21 dias com penicilina cristalina. Recebeu alta hospitalar em boas condições, em aleitamento materno exclusivo e sem seqüelas neurológicas. O caso descrito apresenta como peculiaridades: etiologia incomum de meningite neonatal e evolução favorável, apesar dos relatos em literatura mostrarem seqüelas neurológicas. Destaca-se ainda, a

  17. 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.

  18. 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.

  19. 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)

  20. A misleading urethral smear with polymorphonuclear leucocytes and intracellular diplococci; case report of urethritis caused by Neisseria meningitidis.

    Science.gov (United States)

    Genders, R E; Spitaels, D; Jansen, C L; van den Akker, Th W; Quint, K D

    2013-12-01

    The primary pathogens found in men with urethritis are Chlamydia trachomatis and Neisseria gonorrhoeae. Rapid diagnosis of N. gonorrhoeae infection can be made based on a Gram- or methylene blue-stained urethral smear. We describe a case of a man with purulent penile discharge, in which microscopic examination led to the presumptive diagnosis of gonorrhoea. A nucleic acid amplification test was negative for N. gonorrhoeae but positive for C. trachomatis. Culture showed Gram-negative diplococci which were identified as Neisseria meningitidis. N. meningitidis can be sporadically pathogenic in the genito-urinary tract and mimicks gonococcal urethritis, and appears identical by microscopy. When a gonococcal urethritis is suspected based on clinical signs and microscopic examination, but investigatory tests cannot confirm the diagnosis, a N. meningitidis infection should be considered.

  1. Cognitive Control of Episodic Memory in Schizophrenia: Differential Role of Dorsolateral and Ventrolateral Prefrontal Cortex

    Directory of Open Access Journals (Sweden)

    J Daniel eRagland

    2015-11-01

    Full Text Available Background. Dorsal (DLPFC and ventral (VLPFC subregions in lateral prefrontal cortex play distinct roles in episodic memory, and both are implicated in schizophrenia. We test the hypothesis that schizophrenia differentially impairs DLPFC versus VLPFC control of episodic encoding. Methods. Cognitive control was manipulated by requiring participants to encode targets and avoid encoding nontargets based upon stimulus properties of test stimuli (i.e., the match or miss-match of the color of the word and a surrounding frame. The more automatic encoding response (target versus nontarget was predicted to engage VLPFC in both groups. Conversely, having to overcome the prepotent encoding response (nontargets versus targets was predicted to produce greater DLPFC activation in controls than in patients. Encoding occurred during event-related fMRI in a sample of 21 individuals with schizophrenia and 30 healthy participants. Scanning was followed by recognition testing outside the scanner. Results. Patients were less successful differentially remembering target versus non-target stimuli, and retrieval difficulties correlated with more severe disorganized symptoms. As predicted, the target versus nontarget contrast activated the VLPFC and correlated with retrieval success in both groups. Conversely, the nontarget versus target contrast produced greater DLPFC activation in controls than in patients, and DLPFC activation correlated with performance only in controls.Conclusions. Individuals with schizophrenia can successfully engage the VLPFC to provide control over semantic encoding of individual items, but are specifically impaired at engaging the DLPFC to provide control over rule-guided encoding decisions. This extends previous cognitive control models based on response selection tasks to the memory domain.

  2. 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.

  3. 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

  4. Echolocation calls and communication calls are controlled differentially in the brainstem of the bat Phyllostomus discolor

    Science.gov (United States)

    Fenzl, Thomas; Schuller, Gerd

    2005-01-01

    Background Echolocating bats emit vocalizations that can be classified either as echolocation calls or communication calls. Neural control of both types of calls must govern the same pool of motoneurons responsible for vocalizations. Electrical microstimulation in the periaqueductal gray matter (PAG) elicits both communication and echolocation calls, whereas stimulation of the paralemniscal area (PLA) induces only echolocation calls. In both the PAG and the PLA, the current thresholds for triggering natural vocalizations do not habituate to stimuli and remain low even for long stimulation periods, indicating that these structures have relative direct access to the final common pathway for vocalization. This study intended to clarify whether echolocation calls and communication calls are controlled differentially below the level of the PAG via separate vocal pathways before converging on the motoneurons used in vocalization. Results Both structures were probed simultaneously in a single experimental approach. Two stimulation electrodes were chronically implanted within the PAG in order to elicit either echolocation or communication calls. Blockade of the ipsilateral PLA site with iontophoretically application of the glutamate antagonist kynurenic acid did not impede either echolocation or communication calls elicited from the PAG. However, blockade of the contralateral PLA suppresses PAG-elicited echolocation calls but not communication calls. In both cases the blockade was reversible. Conclusion The neural control of echolocation and communication calls seems to be differentially organized below the level of the PAG. The PLA is an essential functional unit for echolocation call control before the descending pathways share again the final common pathway for vocalization. PMID:16053533

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

    OpenAIRE

    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

    2016-01-01

    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 combin...

  6. Detección de cepas de Neisseria meningitidis resistentes a rifampicina en el Uruguay Detection of rifampicin-resistant strains of Neisseria meningitidis in Uruguay

    Directory of Open Access Journals (Sweden)

    Gabriel Pérez Giffoni

    2011-12-01

    Full Text Available El objetivo de este trabajo fue caracterizar fenotípica y genotípicamente dos aislamientos de Neisseria meningitidis resistentes a rifampicina relacionados con dos eventos independientes de transmisión de enfermedad meningocócica grave que se presentaron en septiembre y octubre de 2010 en Montevideo, Uruguay. Se revisó también la base de datos de la vigilancia nacional de resistencia a los antimicrobianos de los últimos 10 años, para estimar la frecuencia de la particularidad de los meningococos caracterizados. La resistencia a rifampicina se estudió por el método epsilométrico. El serotipo y serosubtipo de los aislamientos se determinaron por ELISA y la caracterización genotípica se realizó por digestión del ADN con NheI y electroforesis en gel con campo pulsátil. Ambos aislamientos eran idénticos, B:2a:P1.5, y su fenotipo no figuraba en la colección de 408 cepas de N. meningitidis aisladas en el Uruguay en los últimos 10 años, con la excepción de dos aislamientos sensibles a rifampicina. Los dos aislamientos estudiados también compartían un pulsotipo único, diferente del de otros dos aislamientos resistentes a rifampicina obtenidos en 2003 y 2007. Por lo tanto, ambos eventos de transmisión fueron causados por una única cepa resistente a rifampicina, que podría haberse introducido al país desde otras regiones o haberse originado por un cambio del serogrupo C al B, como producto de la presión selectiva ejercida por vacunas administradas a la población. Es necesario mantener y extremar la vigilancia. No obstante, en vista de que hasta el momento este tipo de hallazgo ha sido esporádico, no se justifica cambiar el fármaco antimicrobiano que se administra a los contactos para la profilaxis, a menos que se identifique un caso secundario.The objective of this study was to characterize the phenotype and genotype of two isolates of rifampicin-resistant Neisseria meningitidis associated with two independent events

  7. 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

    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......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...

  8. Neisseria meningitidis and Escherichia coli are protected from leukocyte phagocytosis by binding to erythrocyte complement receptor 1 in human blood

    DEFF Research Database (Denmark)

    Brekke, O. L.; Hellerud, B. C.; Christiansen, D.

    2011-01-01

    The initial interaction of Gram-negative bacteria with erythrocytes and its implications on leukocyte phagocytosis and oxidative burst in human whole blood were examined. Alexa-labeled Escherichia coli, wild-type H44/76 N. meningitidis and the H44/76lpxA lipopolysaccharide (LPS)-deficient mutant...... no effect on these processes since similar results were obtained using an LPS-deficient N. meningitidis mutant. In vivo experiments in a pig model of sepsis showed limited binding of bacteria to erythrocytes, consistent with the facts that erythrocyte CR1 receptors are absent in non...

  9. Host iron binding proteins acting as niche indicators for Neisseria meningitidis.

    Directory of Open Access Journals (Sweden)

    Philip W Jordan

    Full Text Available Neisseria meningitidis requires iron, and in the absence of iron alters its gene expression to increase iron acquisition and to make the best use of the iron it has. During different stages of colonization and infection available iron sources differ, particularly the host iron-binding proteins haemoglobin, transferrin, and lactoferrin. This study compared the transcriptional responses of N. meningitidis, when grown in the presence of these iron donors and ferric iron, using microarrays.Specific transcriptional responses to the different iron sources were observed, including genes that are not part of the response to iron restriction. Comparisons between growth on haemoglobin and either transferrin or lactoferrin identified changes in 124 and 114 genes, respectively, and 33 genes differed between growth on transferrin or lactoferrin. Comparison of gene expression from growth on haemoglobin or ferric iron showed that transcription is also affected by the entry of either haem or ferric iron into the cytoplasm. This is consistent with a model in which N. meningitidis uses the relative availability of host iron donor proteins as niche indicators.Growth in the presence of haemoglobin is associated with a response likely to be adaptive to survival within the bloodstream, which is supported by serum killing assays that indicate growth on haemoglobin significantly increases survival, and the response to lactoferrin is associated with increased expression of epithelial cell adhesins and oxidative stress response molecules. The transferrin receptor is the most highly transcribed receptor and has the fewest genes specifically induced in its presence, suggesting this is the favoured iron source for the bacterium. Most strikingly, the responses to haemoglobin, which is associated with unrestricted growth, indicates a low iron transcriptional profile, associated with an aggressive phenotype that may be adaptive to access host iron sources but which may also

  10. Use of Restriction Fragment Length Polymorphisms to Investigate Strain Variation Within Neisseria Meningitidis.

    Science.gov (United States)

    Williams, Shelley Diane

    Similarity within bacterial populations is difficult to assess due to the limited number of characters available for evaluation and the heterogeneity of bacterial species. Currently, the preferred method used to evaluate the structure of bacterial populations is multilocus enzyme electrophoresis. However, this method is extremely cumbersome and only offers an indirect measure of genetic similarities. The development of a more direct and less cumbersome method for this purpose is warranted. Restriction fragment length polymorphism analysis was evaluated as a tool for use in the study of bacterial population structures and in the epidemiology and surveillance of infectious disease. A collection of Neisseria meningitidis was available for use in the investigation of this technique. Neisseria meningitidis is the causative agent of epidemic cerebrospinal meningitis and septicemia as well as a variety of other clinical manifestations. Each isolate in the collection was defined in terms of serogroup specificity, clinical history, geographic source, and date of isolation. Forty -six strains were chosen for this study. The DNA from each strain was restricted with Pst1 and EcoR1 and electrophoresed on agarose gels. The DNA was transferred to nylon filters and hybridized with P ^{32} labeled DNA probes. Two randomly generated probes and a gene-specific probe were used to estimate the genetic similarities between and among the strains in the study population. A total of 28 different restriction fragment migration types were detected by the probes used. Data obtained from the RFLP analysis was analysed by cluster analysis and multivariate statistical methods. A total of 7 clones groups were detected. Two of these appear to be major clones that comprise 35% of the population. This analysis demonstrates the lack of structure within Neisseria meningitidis due primarily to a heterogenous population and the lack of geographic segregation. The potential utility of this technique as a

  11. 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.

  12. Averaging of Differential Equations Generating Oscillations and an Application to Control

    International Nuclear Information System (INIS)

    Temam, R.M.; Wirosoetisno, D.

    2002-01-01

    In this article we consider differential equations which generate oscillating solutions. These oscillations are due to the presence of a small parameter ε>0 ; however, they are not present in the coefficients but instead they are caused by a penalty term involving an antisymmetric operator. Our aims are twofold. In the first part we study asymptotics at all orders, for ε → 0 , construct approximate solutions, and derive estimates of the error between the exact solution and the approximate ones. One of the motivations of this part is the study to high orders of the geostrophic asymptotics in atmospheric science, but there are many other possible applications involving in particular the wave equation. The actual applications of our results to atmospheric science will be discussed elsewhere [STW], as well as, on the mathematical side, the application to partial differential equations [TW1]. In the second part of this article we study a control problem involving such an equation and study the behavior of the state equation, of the optimal control, and of the optimality equation as ε → 0 . For the control part we restrict ourselves to a linear equation and to the first order in the asymptotics ε → 0 , leaving nonlinear problems and higher orders to a future work

  13. Neisseria meningitidis: a neglected cause of infectious haemorrhagic fever in the amazon rainforest.

    Science.gov (United States)

    Barroso, David E; Silva, Luciete A

    2007-12-01

    Neisseria meningitidis has not been seen as a significant cause of infectious haemorrhagic fever in the Amazon inlands; most reported cases are from the city of Manaus, the capital of the State of Amazonas. This picture is sustained by the lack of reliable microbiology laboratories, the perception of the health care workers, and the difficult to reach medical assistance; thus the number of confirmed cases is even lower with no reference of the strains phenotype. We report here the investigation of a case of suspected meningococcemia and his close contacts in a rural community in the Coari Lake, up the Amazon River.

  14. NMR resonance assignments of NarE, a putative ADP-ribosylating toxin from Neisseria meningitidis

    OpenAIRE

    Carlier, Ludovic; Koehler, Christian; Veggi, Daniele; Pizza, Mariagrazia; Soriani, Marco; Boelens, Rolf; Bonvin, Alexandre M. J. J.

    2010-01-01

    NarE is a 16 kDa protein identified from Neisseria meningitidis, one of the bacterial pathogens responsible for meningitis. NarE belongs to the ADP-ribosyltransferase family and catalyses the transfer of ADP-ribose moieties to arginine residues in target protein acceptors. Many pathogenic bacteria utilize ADP-ribosylating toxins to modify and alter essential functions of eukaryotic cells. NarE was proposed to bind iron through a Fe–S center which is supposed to be implied in catalysis. We hav...

  15. Paracrine control of differentiation in the alveolar carcinoma, A549, by human foetal lung fibroblasts.

    Science.gov (United States)

    Speirs, V; Ray, K P; Freshney, R I

    1991-10-01

    Synthesis of pulmonary surfactant (PS) is necessary for normal functioning of the lungs and its production is indicative of normal differentiated lung. The human alveolar carcinoma, A549, has been found to synthesis and secrete PS in vitro. The purpose of this study was to optimise the culture conditions for PS synthesis by A549 as well as to determine the potential role of foetal lung fibroblasts in the induction of PS by glucocorticoids. A549 cells growing in filter wells produced higher levels of PS in response to steroid, a 5-fold increase on the filter well compared to only a 1.5-fold increase when the cells were cultured on a conventional plastic substrate. A549 cells grown in filter wells responded to coculture with fibroblasts whether in direct contact or separated co-culture. A 20-fold increase in PS over control values was observed in separated steroid-treated co-cultures, suggesting the presence of a diffusible factor. A partially purified factor was isolated from fibroblast conditioned medium which was capable of inducing differentiation and other phenotypic changes in A549, namely induction of PS, reduction of plasminogen activator activity and reduction in the in vivo growth of A549 xenografts in nude mice. These results suggest that, under the correct conditions, A549 cells, although transformed, still retain the capacity to respond to differentiation-inducing signals from normal fibroblasts.

  16. 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

  17. 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.

  18. Realization of Resistorless Wave Active Filter using Differential Voltage Current Controlled Conveyor Transconductance Amplifier

    Directory of Open Access Journals (Sweden)

    N. Pandey

    2011-12-01

    Full Text Available In this paper, a resistorless realization of high order voltage mode wave active filter based on Differential Voltage current controlled conveyor transconductance amplifier (DVCCCTA is presented. The wave method is used for simulating reflected and incident wave for basic building block i.e. series inductor and configuring it for other passive element realization by making appropriate connection. The proposed structure uses grounded capacitors and possesses electronic tunability of cutoff frequency. The proposed approach is verified for a 4th order low pass filter through SPICE simulation using 0.25µm TSMC CMOS technology parameters.

  19. 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.

  20. 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.

  1. Retro-Prospective Differential Inclusions and their Control by the Differential Connection Tensors of their Evolutions: The trendometer

    OpenAIRE

    Aubin, Jean-Pierre

    2013-01-01

    This study is motivated by two different, yet, connected, motivations. The first one follows the observation that the classical definition of derivatives involves prospective (or forward) difference quotients, not known whenever the time is directed, at least at the macroscopic level. Actually, the available and known derivatives are retrospective (or backward). They co\\"incide whenever the functions are differentiable in the classical sense, but not in the case of non smooth maps, single-val...

  2. Outbreak of serotype W135 Neisseria meningitidis in central river ...

    African Journals Online (AJOL)

    2012-06-21

    Jun 21, 2012 ... References. 1. Gambia Ministry of Health and Social welfare. Epidemiology and disease control unit Banjul; 2012. 2. World Health Organization. Control of epidemic meningococcal disease. In: Practical Guidelines. 2nd ed. Geneva: World Health Organization; 1998. Available from: http://www.who.int/emc.

  3. A prospective comparative study between differential moments and miniscrews in anchorage control.

    Science.gov (United States)

    Davoody, Amirparviz R; Posada, Laura; Utreja, Achint; Janakiraman, Nandakumar; Neace, William P; Uribe, Flavio; Nanda, Ravindra

    2013-10-01

    The purpose of this study was to measure the efficacy of anchorage control between differential moments mechanics and temporary anchorage devices in a clinical trial. Forty-six patients requiring extraction of maxillary first premolars were allocated into 2 treatment groups. The differential moments group (G1) received a nickel titanium (NiTi) intrusion arch and a 150g NiTi closing coil spring for separate canine retraction, followed by a continuous mushroom loop archwire for the retraction of the incisors. The TAD group (G2) received one miniscrew placed between maxillary second premolars and first molars with a 150 g NiTi closing coil spring connecting the miniscrew to a hook placed in the archwire between the lateral incisor and canine. Lateral cephalograms were taken before (T1) and after incisor retraction (T2). The ratio of molar protraction to incisor retraction was calculated and intragroup and intergroup changes in upper lip, maxillary incisor and molar position were analyzed by paired and independent t-tests. Twenty-eight patients were analyzed after 18 patients did not receive the intervention, were lost to follow-up, or discontinued treatment. The ratio of molar protraction to incisor retraction in G1 was 0.44 and in G2 was -0.11, which was significantly different. There was a statistically significant change in upper lip from T1 to T2 but no difference between the two groups. Moreover, there was a significant distal molar tipping and lingual incisor tipping in G2. There is a significant difference in the amount of anchorage control using differential moments mechanics compared to TADs. Although statistically significant retraction of upper lip was observed in both groups, there was no significant difference between the two groups.

  4. 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.

  5. 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.

  6. Echolocation calls and communication calls are controlled differentially in the brainstem of the bat Phyllostomus discolor

    Directory of Open Access Journals (Sweden)

    Schuller Gerd

    2005-08-01

    Full Text Available Abstract Background Echolocating bats emit vocalizations that can be classified either as echolocation calls or communication calls. Neural control of both types of calls must govern the same pool of motoneurons responsible for vocalizations. Electrical microstimulation in the periaqueductal gray matter (PAG elicits both communication and echolocation calls, whereas stimulation of the paralemniscal area (PLA induces only echolocation calls. In both the PAG and the PLA, the current thresholds for triggering natural vocalizations do not habituate to stimuli and remain low even for long stimulation periods, indicating that these structures have relative direct access to the final common pathway for vocalization. This study intended to clarify whether echolocation calls and communication calls are controlled differentially below the level of the PAG via separate vocal pathways before converging on the motoneurons used in vocalization. Results Both structures were probed simultaneously in a single experimental approach. Two stimulation electrodes were chronically implanted within the PAG in order to elicit either echolocation or communication calls. Blockade of the ipsilateral PLA site with iontophoretically application of the glutamate antagonist kynurenic acid did not impede either echolocation or communication calls elicited from the PAG. However, blockade of the contralateral PLA suppresses PAG-elicited echolocation calls but not communication calls. In both cases the blockade was reversible. Conclusion The neural control of echolocation and communication calls seems to be differentially organized below the level of the PAG. The PLA is an essential functional unit for echolocation call control before the descending pathways share again the final common pathway for vocalization.

  7. Adaptive Neural Control Based on High Order Integral Chained Differentiator for Morphing Aircraft

    Directory of Open Access Journals (Sweden)

    Zhonghua Wu

    2015-01-01

    Full Text Available This paper presents an adaptive neural control for the longitudinal dynamics of a morphing aircraft. Based on the functional decomposition, it is reasonable to decompose the longitudinal dynamics into velocity and altitude subsystems. As for the velocity subsystem, the adaptive control is proposed via dynamic inversion method using neural network. To deal with input constraints, the additional compensation system is employed to help engine recover from input saturation rapidly. The highlight is that high order integral chained differentiator is used to estimate the newly defined variables and an adaptive neural controller is designed for the altitude subsystem where only one neural network is employed to approximate the lumped uncertain nonlinearity. The altitude subsystem controller is considerably simpler than the ones based on backstepping. It is proved using Lyapunov stability theory that the proposed control law can ensure that all the tracking error converges to an arbitrarily small neighborhood around zero. Numerical simulation study demonstrates the effectiveness of the proposed strategy, during the morphing process, in spite of some uncertain system nonlinearity.

  8. N. meningitidis 1681 is a member of the FinO family of RNA chaperones.

    Energy Technology Data Exchange (ETDEWEB)

    Chaulk, S.; Lu, J.; Tan, K.; Arthur, D.; Edwards, R.; Frost, L.; Joachimiak, A.; Glover, J. (Biosciences Division); (Univ. of Alberta)

    2010-11-01

    The conjugative transfer of F-like plasmids between bacteria is regulated by the plasmid-encoded RNA chaperone, FinO, which facilitates sense - antisense RNA interactions to regulate plasmid gene expression. FinO was thought to adopt a unique structure, however many putative homologs have been identified in microbial genomes and are considered members of the FinO-conjugation-repressor superfamily. We were interested in determining whether other members were also able to bind RNA and promote duplex formation, suggesting that this motif does indeed identify a putative RNA chaperone. We determined the crystal structure of the N. meningitidis MC58 protein NMB1681. It revealed striking similarity to FinO, with a conserved fold and a large, positively charged surface that could function in RNA interactions. Using assays developed to study FinO-FinP sRNA interactions, NMB1681, like FinO, bound tightly to FinP RNA stem-loops with short 5-foot and 3-foot single-stranded tails but not to ssRNA. It also was able to catalyze strand exchange between an RNA duplex and a complementary single-strand, and facilitated duplexing between complementary RNA hairpins. Finally, NMB1681 was able to rescue a finO deficiency and repress F plasmid conjugation. This study strongly suggests that NMB1681 is a FinO-like RNA chaperone that likely regulates gene expression through RNA-based mechanisms in N. meningitidis.

  9. Refolding, purification and crystallization of the FrpB outer membrane iron transporter from Neisseria meningitidis

    International Nuclear Information System (INIS)

    Saleem, Muhammad; Prince, Stephen M.; Patel, Hema; Chan, Hannah; Feavers, Ian M.; Derrick, Jeremy P.

    2012-01-01

    The refolding, purification and crystallization of FrpB from the meningitis pathogen Neisseria meningitidis is described. FrpB is an integral outer membrane protein from the human pathogen Neisseria meningitidis. It is a member of the TonB-dependent transporter family and promotes the uptake of iron across the outer membrane. There is also evidence that FrpB is an antigen and hence a potential component of a vaccine against meningococcal meningitis. FrpB incorporating a polyhistidine tag was overexpressed in Escherichia coli into inclusion bodies. The protein was then solubilized in urea, refolded and purified to homogeneity. Two separate antigenic variants of FrpB were crystallized by sitting-drop vapour diffusion. Crystals of the F5-1 variant diffracted to 2.4 Å resolution and belonged to space group C2, with unit-cell parameters a = 176.5, b = 79.4, c = 75.9 Å, β = 98.3°. Crystal-packing calculations suggested the presence of a monomer in the asymmetric unit. Crystals of the F3-3 variant also diffracted to 2.4 Å resolution and belonged to space group P2 1 2 1 2 1 , with unit-cell parameters a = 85.3, b = 104.6, c = 269.1 Å. Preliminary analysis suggested the presence of an FrpB trimer in the asymmetric unit

  10. Molecular biology of Neisseria meningitidis class 5 and H. 8 outer membrane proteins

    Energy Technology Data Exchange (ETDEWEB)

    Kawula, T.H.

    1987-01-01

    One of the surface structures responsible for inter- and intrastrain antigenic variability in meningococci is the heat-modifiable class 5 (C.5) protein. Neisseria meningitidis strain FAM18 (a meningococcal disease isolate) expressed two different C.5 proteins (C.5a and C.5b) identifiable by sodium dodecyl sulfate polyacrylamide gel electrophoresis. We generated two monoclonal antibodies (MAbs), each specific for one of the identified C.5 proteins. The MAbs, which were bactericidal for variants expressing the appropriate C.5 protein, were used to study C.5 expression changes in FAM18. The H.8 protein is an antigenically conserved outer membrane protein expressed almost exclusively by the pathogenic Neisseria. We have cloned and sequenced an H.8 gene from N. meningitidis FAM18. The predicted H.8 amino acid sequence indicated that the most probable signal peptide processing site matched the consensus prokaryotic lipoprotein processing/modification sequence. We then showed that the H.8 protein could be labeled with {sup 14}C-palmitic acid, confirming that H.8 was a lipoprotein. Processing of the H.8 protein was inhibited by globomycin in E. coli indicating that H.8 was modified by the described lipoprotein processing/modifying pathway described in both gram negative and gram positive genera.

  11. Structural basis for solute transport, nucleotide regulation, and immunological recognition of Neisseria meningitidis PorB

    Energy Technology Data Exchange (ETDEWEB)

    Tanabe, Mikio; Nimigean, Crina M.; Iverson, T.M. (Weill-Med); (Vanderbilt)

    2010-06-25

    PorB is the second most prevalent outer membrane protein in Neisseria meningitidis. PorB is required for neisserial pathogenesis and can elicit a Toll-like receptor mediated host immune response. Here, the x-ray crystal structure of PorB has been determined to 2.3 {angstrom} resolution. Structural analysis and cocrystallization studies identify three putative solute translocation pathways through the channel pore: One pathway transports anions nonselectively, one transports cations nonselectively, and one facilitates the specific uptake of sugars. During infection, PorB likely binds host mitochondrial ATP, and cocrystallization with the ATP analog AMP-PNP suggests that binding of nucleotides regulates these translocation pathways both by partial occlusion of the pore and by restricting the motion of a putative voltage gating loop. PorB is located on the surface of N. meningitidis and can be recognized by receptors of the host innate immune system. Features of PorB suggest that Toll-like receptor mediated recognition outer membrane proteins may be initiated with a nonspecific electrostatic attraction.

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

    Science.gov (United States)

    Mazandarani, Mehran; Pariz, Naser

    2018-03-16

    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.

  13. Adhesion of Neisseria meningitidis to Dermal Vessels Leads to Local Vascular Damage and Purpura in a Humanized Mouse Model

    Science.gov (United States)

    Melican, Keira; Michea Veloso, Paula; Martin, Tiffany; Bruneval, Patrick; Duménil, Guillaume

    2013-01-01

    Septic shock caused by Neisseria meningitidis is typically rapidly evolving and often fatal despite antibiotic therapy. Further understanding of the mechanisms underlying the disease is necessary to reduce fatality rates. Postmortem samples from the characteristic purpuric rashes of the infection show bacterial aggregates in close association with microvessel endothelium but the species specificity of N. meningitidis has previously hindered the development of an in vivo model to study the role of adhesion on disease progression. Here we introduced human dermal microvessels into SCID/Beige mice by xenografting human skin. Bacteria injected intravenously exclusively associated with the human vessel endothelium in the skin graft. Infection was accompanied by a potent inflammatory response with the secretion of human inflammatory cytokines and recruitment of inflammatory cells. Importantly, infection also led to local vascular damage with hemostasis, thrombosis, vascular leakage and finally purpura in the grafted skin, replicating the clinical presentation for the first time in an animal model. The adhesive properties of the type IV pili of N. meningitidis were found to be the main mediator of association with the dermal microvessels in vivo. Bacterial mutants with altered type IV pili function also did not trigger inflammation or lead to vascular damage. This work demonstrates that local type IV pili mediated adhesion of N. meningitidis to the vascular wall, as opposed to circulating bacteria, determines vascular dysfunction in meningococcemia. PMID:23359320

  14. Mannose binding lectin enhances IL-1beta and IL-10 induction by non-lipopolysaccharide (LPS) components of Neisseria meningitidis.

    NARCIS (Netherlands)

    Sprong, T.; Jack, D.L.; Klein, N.J.; Turner, M.W.; Ley, P. van der; Steeghs, L.; Jacobs, L.; Meer, J.W.M. van der; Deuren, M. van

    2004-01-01

    Mannose binding lectin (MBL) is a key molecule in the lectin pathway of complement activation, and likely of importance in our innate defence against meningococcal infection. We evaluated the role of MBL in cytokine induction by LPS or non-LPS components of Neisseria meningitidis, using a

  15. Opa+ and Opa- isolates of Neisseria meningitidis and Neisseria gonorrhoeae induce sustained proliferative responses in human CD4+ T cells.

    NARCIS (Netherlands)

    Youssef, A.R.; Flier, M. van der; Estevao, S.; Hartwig, N.G.; Ley, P. van der; Virji, M.

    2009-01-01

    T cells may interact with a number of bacterial surface antigens, an encounter which has the potential to downmodulate host immune responses. Neisseria meningitidis, a human colonizer and an agent of septicemia and meningitis, expresses Opa proteins which interact with the CEACAM1 receptor expressed

  16. Representational difference analysis of Neisseria meningitidis identifies sequences that are specific for the hyper-virulent lineage III clone

    NARCIS (Netherlands)

    Bart, A.; Dankert, J.; van der Ende, A.

    2000-01-01

    Neisseria meningitidis may cause meningitis and septicemia. Since the early 1980s, an increased incidence of meningococcal disease has been caused by the lineage III clone in many countries in Europe and in New Zealand. We hypothesized that lineage III meningococci have specific DNA sequences,

  17. NmeSI restriction-modification system identified by representational difference analysis of a hypervirulent Neisseria meningitidis strain

    NARCIS (Netherlands)

    Bart, A.; Pannekoek, Y.; Dankert, J.; van der Ende, A.

    2001-01-01

    Neisseria meningitidis is a gram-negative bacterium that may cause meningitis, sepsis, or both. The increase in the incidence of meningococcal disease in various countries in the past 2 decades is mainly due the genotypically related lineage III meningococci. The chromosomal DNA differences between

  18. Phenotypic and genotypic changes in a new clone complex of Neisseria meningitidis causing disease in The Netherlands, 1958-1990

    NARCIS (Netherlands)

    Scholten, R. J.; Poolman, J. T.; Valkenburg, H. A.; Bijlmer, H. A.; Dankert, J.; Caugant, D. A.

    1994-01-01

    To characterize the phenotypic and genotypic changes that occurred in a new clone lineage of Neisseria meningitidis (lineage III) in the Netherlands, the electrophoretic type (ET) was determined for 79 serogroup B isolates of serotype 4 or subtype P1.4 (or both) obtained between 1958 and 1990 from

  19. NMR assignment of intrinsically disordered self-processing module of the FrpC protein of Neisseria meningitidis

    Czech Academy of Sciences Publication Activity Database

    Kubáň, V.; Nováček, J.; Bumba, Ladislav; Žídek, L.

    2015-01-01

    Roč. 9, č. 2 (2015), s. 435-440 ISSN 1874-2718 R&D Projects: GA ČR(CZ) GAP207/11/0717 Institutional support: RVO:61388971 Keywords : FrpC * Self-processing module * Neisseria meningitidis Subject RIV: EE - Microbiology, Virology Impact factor: 0.687, year: 2015

  20. Self-esteem in children and adolescents after septic shock caused by Neisseria meningitidis: scars do matter

    NARCIS (Netherlands)

    Vermunt, Lindy C.; Buysse, Corinne M.; Joosten, Koen F.; Oranje, Arnold P.; Hazelzet, Jan A.; Verhulst, Frank C.; Utens, Elisabeth M.

    2008-01-01

    To investigate self-esteem and its relation to scars, amputations, and orthopedic sequelae in children and adolescents long term after meningococcal septic shock (MSS) caused by Neisseria meningitidis. The Dutch versions of the Self-Perception Profile for Children (SPP-C; 8-11 years) and the

  1. Complete Genome Sequence of Neisseria meningitidis Serogroup A Strain NMA510612, Isolated from a Patient with Bacterial Meningitis in China

    OpenAIRE

    Zhang, Yan; Yang, Jian; Xu, Li; Zhu, Yafang; Liu, Bo; Shao, Zhujun; Zhang, Xiaobing; Jin, Qi

    2014-01-01

    Serogroup A meningococcal strains have been involved in several pandemics and a series of epidemics worldwide in the past. Determination of the genome sequence of the prevalent genotype strain will help us understand the genetic background of the evolutionary and epidemiological properties of these bacteria. We sequenced the complete genome of Neisseria meningitidis NMA510612, a clinical isolate from a patient with meningococcal meningitis.

  2. Meningitis caused by Neisseria Meningitidis, Hemophilus Influenzae Type B and Streptococcus Pneumoniae during 2005–2012 in Turkey

    Science.gov (United States)

    Ceyhan, Mehmet; Gürler, Nezahat; Ozsurekci, Yasemin; Keser, Melike; Aycan, Ahmet Emre; Gurbuz, Venhar; Salman, Nuran; Camcioglu, Yildiz; Dinleyici, Ener Cagri; Ozkan, Sengul; Sensoy, Gulnar; Belet, Nursen; Alhan, Emre; Hacimustafaoglu, Mustafa; Celebi, Solmaz; Uzun, Hakan; Faik Oner, Ahmet; Kurugol, Zafer; Ali Tas, Mehmet; Aygun, Denizmen; Oncel, Eda Karadag; Celik, Melda; Yasa, Olcay; Akin, Fatih; Coşkun, Yavuz

    2014-01-01

    Successful vaccination policies for protection from bacterial meningitis are dependent on determination of the etiology of bacterial meningitis. Cerebrospinal fluid (CSF) samples were obtained prospectively from children from 1 month to ≤ 18 years of age hospitalized with suspected meningitis, in order to determine the etiology of meningitis in Turkey. DNA evidence of Neisseria meningitidis (N. meningitidis), Streptococcus pneumoniae (S. pneumoniae), and Hemophilus influenzae type b (Hib) was detected using multiplex polymerase chain reaction (PCR). In total, 1452 CSF samples were evaluated and bacterial etiology was determined in 645 (44.4%) cases between 2005 and 2012; N. meningitidis was detected in 333 (51.6%), S. pneumoniae in 195 (30.2%), and Hib in 117 (18.1%) of the PCR positive samples. Of the 333 N. meningitidis positive samples 127 (38.1%) were identified as serogroup W-135, 87 (26.1%) serogroup B, 28 (8.4%) serogroup A and 3 (0.9%) serogroup Y; 88 (26.4%) were non-groupable. As vaccines against the most frequent bacterial isolates in this study are available and licensed, these results highlight the need for broad based protection against meningococcal disease in Turkey. PMID:25483487

  3. Improved OMV vaccine against Neisseria meningitidis using genetically engineered strains and a detergent-free purification process

    NARCIS (Netherlands)

    Waterbeemd, van de B.; Streefland, M.; Ley, de P.; Zomer, B.; Dijken, van H.; Martens, D.E.; Wijffels, R.H.; Pol, van der L.A.

    2010-01-01

    The use of detergent-extracted outer membrane vesicles (OMVs) is an established approach for development of a multivalent PorA vaccine against N. meningitidis serogroup B. Selective removal of lipopolysaccharide (LPS) decreases toxicity, but promotes aggregation and narrows the immune response.

  4. Outbreak of serotype W135 Neisseria meningitidis in central river ...

    African Journals Online (AJOL)

    2012-06-21

    Jun 21, 2012 ... program on immunization schedule of the Gambia and other countries within the meningitic epidemic belt. Key words: Neisseria ... The African meningitis belt extends from Ethiopia in the. East, to Senegal in the West within ..... surveillance and management system at the national level for effective control of ...

  5. 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

  6. The Structure, Design, and Closed-Loop Motion Control of a Differential Drive Soft Robot.

    Science.gov (United States)

    Wu, Pang; Jiangbei, Wang; Yanqiong, Fei

    2018-02-01

    This article presents the structure, design, and motion control of an inchworm inspired pneumatic soft robot, which can perform differential movement. This robot mainly consists of two columns of pneumatic multi-airbags (actuators), one sensor, one baseboard, front feet, and rear feet. According to the different inflation time of left and right actuators, the robot can perform both linear and turning movements. The actuators of this robot are composed of multiple airbags, and the design of the airbags is analyzed. To deal with the nonlinear performance of the soft robot, we use radial basis function neural networks to train the turning ability of this robot on three different surfaces and create a mathematical model among coefficient of friction, deflection angle, and inflation time. Then, we establish the closed-loop automatic control model using three-axis electronic compass sensor. Finally, the automatic control model is verified by linear and turning movement experiments. According to the experiment, the robot can finish the linear and turning movements under the closed-loop control system.

  7. Antigen sequence typing of outer membrane protein (fetA gene of Neisseria meningitidis serogroup A from Delhi & adjoining areas

    Directory of Open Access Journals (Sweden)

    S Dwivedi

    2014-01-01

    Full Text Available Background & objectives: Meningitis caused by Neisseria meningitidis is a fatal disease. Meningococcal meningitis is an endemic disease in Delhi and irregular pattern of outbreaks has been reported in India. All these outbreaks were associated with serogroup A. Detailed molecular characterization of N. meningitidis is required for the management of this fatal disease. In this study, we characterized antigenic diversity of surface exposed outer membrane protein (OMP FetA antigen of N. meningitidis serogroup A isolates obtained from cases of invasive meningococcal meningitis in Delhi, India. Methods: Eight isolates of N. meningitidis were collected from cerebrospinal fluid during October 2008 to May 2011 from occasional cases of meningococcal meningitis. Seven isolates were from outbreaks of meningococcal meningitis in 2005-2006 in Delhi and its adjoining areas. These were subjected to molecular typing of fetA gene, an outer membrane protein gene. Results: All 15 N. meningitides isolates studied were serogroup A. This surface exposed porin is putatively under immune pressure. Hence as a part of molecular characterization, genotyping was carried out to find out the diversity in outer membrane protein (FetA gene among the circulating isolates of N. meningitidis. All 15 isolates proved to be of the same existing allele type of FetA variable region (VR when matched with global database. The allele found was F3-1 for all the isolates. Interpretation & conclusions: There was no diversity reported in the outer membrane protein FetA in the present study and hence this protein appeared to be a stable molecule. More studies on molecular characterization of FetA antigen are required from different serogroups circulating in different parts of the world.

  8. Optimal Design of Signal Controlled Road Networks Using Differential Evolution Optimization Algorithm

    Directory of Open Access Journals (Sweden)

    Huseyin Ceylan

    2013-01-01

    Full Text Available This study proposes a traffic congestion minimization model in which the traffic signal setting optimization is performed through a combined simulation-optimization model. In this model, the TRANSYT traffic simulation software is combined with Differential Evolution (DE optimization algorithm, which is based on the natural selection paradigm. In this context, the EQuilibrium Network Design (EQND problem is formulated as a bilevel programming problem in which the upper level is the minimization of the total network performance index. In the lower level, the traffic assignment problem, which represents the route choice behavior of the road users, is solved using the Path Flow Estimator (PFE as a stochastic user equilibrium assessment. The solution of the bilevel EQND problem is carried out by the proposed Differential Evolution and TRANSYT with PFE, the so-called DETRANSPFE model, on a well-known signal controlled test network. Performance of the proposed model is compared to that of two previous works where the EQND problem has been solved by Genetic-Algorithms- (GAs- and Harmony-Search- (HS- based models. Results show that the DETRANSPFE model outperforms the GA- and HS-based models in terms of the network performance index and the computational time required.

  9. Jun Dimerization Protein 2 Controls Senescence and Differentiation via Regulating Histone Modification

    Directory of Open Access Journals (Sweden)

    Yu-Chang Huang

    2011-01-01

    Full Text Available Transcription factor, Jun dimerization protein 2 (JDP2, binds directly to histones and DNAs and then inhibits the p300-mediated acetylation both of core histones and of reconstituted nucleosomes that contain JDP2 recognition DNA sequences. JDP2 plays a key role as a repressor of adipocyte differentiation by regulation of the expression of the gene C/EBPδ via inhibition of histone acetylation. Moreover, JDP2-deficient mouse embryonic fibroblasts (JDP2−/− MEFs are resistant to replicative senescence. JDP2 inhibits the recruitment of polycomb repressive complexes (PRC1 and PRC2 to the promoter of the gene encoding p16Ink4a, resulting from the inhibition of methylation of lysine 27 of histone H3 (H3K27. Therefore, it seems that chromatin-remodeling factors, including the PRC complex controlled by JDP2, may be important players in the senescence program. The novel mechanisms that underline the action of JDP2 in inducing cellular senescence and suppressing adipocyte differentiation are reviewed.

  10. The cell polarity determinant CDC42 controls division symmetry to block leukemia cell differentiation.

    Science.gov (United States)

    Mizukawa, Benjamin; O'Brien, Eric; Moreira, Daniel C; Wunderlich, Mark; Hochstetler, Cindy L; Duan, Xin; Liu, Wei; Orr, Emily; Grimes, H Leighton; Mulloy, James C; Zheng, Yi

    2017-09-14

    As a central regulator of cell polarity, the activity of CDC42 GTPase is tightly controlled in maintaining normal hematopoietic stem and progenitor cell (HSC/P) functions. We found that transformation of HSC/P to acute myeloid leukemia (AML) is associated with increased CDC42 expression and activity in leukemia cells. In a mouse model of AML, the loss of Cdc42 abrogates MLL-AF9 -induced AML development. Furthermore, genetic ablation of CDC42 in both murine and human MLL-AF9 (MA9) cells decreased survival and induced differentiation of the clonogenic leukemia-initiating cells. We show that MLL-AF9 leukemia cells maintain cell polarity in the context of elevated Cdc42-guanosine triphosphate activity, similar to nonmalignant, young HSC/Ps. The loss of Cdc42 resulted in a shift to depolarized AML cells that is associated with a decrease in the frequency of symmetric and asymmetric cell divisions producing daughter cells capable of self-renewal. Importantly, we demonstrate that inducible CDC42 suppression in primary human AML cells blocks leukemia progression in a xenograft model. Thus, CDC42 loss suppresses AML cell polarity and division asymmetry, and CDC42 constitutes a useful target to alter leukemia-initiating cell fate for differentiation therapy. © 2017 by The American Society of Hematology.

  11. 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

    2017-01-01

    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. PMID:26950239

  12. 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.

  13. 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.

  14. Urinary Polyamine Biomarker Panels with Machine-Learning Differentiated Colorectal Cancers, Benign Disease, and Healthy Controls.

    Science.gov (United States)

    Nakajima, Tetsushi; Katsumata, Kenji; Kuwabara, Hiroshi; Soya, Ryoko; Enomoto, Masanobu; Ishizaki, Tetsuo; Tsuchida, Akihiko; Mori, Masayo; Hiwatari, Kana; Soga, Tomoyoshi; Tomita, Masaru; Sugimoto, Masahiro

    2018-03-07

    Colorectal cancer (CRC) is one of the most daunting diseases due to its increasing worldwide prevalence, which requires imperative development of minimally or non-invasive screening tests. Urinary polyamines have been reported as potential markers to detect CRC, and an accurate pattern recognition to differentiate CRC with early stage cases from healthy controls are needed. Here, we utilized liquid chromatography triple quadrupole mass spectrometry to profile seven kinds of polyamines, such as spermine and spermidine with their acetylated forms. Urinary samples from 201 CRCs and 31 non-CRCs revealed the N ₁, N 12 -diacetylspermine showing the highest area under the receiver operating characteristic curve (AUC), 0.794 (the 95% confidence interval (CI): 0.704-0.885, p machine learning method using combinations of polyamines showed a higher AUC value of 0.961 (95% CI: 0.937-0.984, p machine-learning method showed potential as a screening tool of CRC.

  15. 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.

  16. 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.

  17. Control of chemical effects in the separation process of a differential mobility mass spectrometer system.

    Science.gov (United States)

    Schneider, Bradley B; Covey, Thomas R; Coy, Stephen L; Krylov, Evgeny V; Nazarov, Erkinjon G

    2010-01-01

    Differential mobility spectrometry (DMS) separates ions on the basis of the difference in their migration rates under high versus low electric fields. Several models describing the physical nature of this field mobility dependence have been proposed but emerging as a dominant effect is the clusterization model sometimes referred to as the dynamic cluster-decluster model. DMS resolution and peak capacity is strongly influenced by the addition of modifiers which results in the formation and dissociation of clusters. This process increases selectivity due to the unique chemical interactions that occur between an ion and neutral gas-phase molecules. It is thus imperative to bring the parameters influencing the chemical interactions under control and find ways to exploit them in order to improve the analytical utility of the device. In this paper, we describe three important areas that need consideration in order to stabilize and capitalize on the chemical processes that dominate a DMS separation. The first involves means of controlling the dynamic equilibrium of the clustering reactions with high concentrations of specific reagents. The second area involves a means to deal with the unwanted heterogeneous cluster ion populations emitted from the electrospray ionization process that degrade resolution and sensitivity. The third involves fine control of parameters that affect the fundamental collision processes, temperature and pressure.

  18. Electrodermal activity at acupuncture points differentiates patients with current pain from pain-free controls.

    Science.gov (United States)

    Turner, Linda; Linden, Wolfgang; Marshall, Candace

    2013-03-01

    This study evaluated whether electrodermal resistance at acupuncture points (AP) systematically varies as a function of pain. The study was conceived as a proof-of-principle study in support of research on acupuncture and other complementary medicine approaches. Specifically, this study investigates whether or not electrodermal activity systematically differentiates arthritis patients with current pain from pain-free controls. Participants with rheumatoid arthritis (n = 32) and a typical pain level of at least 3 (on a 0-10 scale) were compared with case controls (n = 28) who had no medical diagnosis and were pain free. Electrodermal resistance at AP was measured with a commercial ohmmeter and compared to heart rate, blood pressure, and ratings on the Pain Catastrophization Scale and the McGill Melzack Pain Questionnaire. There were consistent differences between the experimental group and the control group on all markers of pain. Similarly, there were significant group differences and some trends for electrodermal activity at the AP labeled 'bladder,' 'gall bladder,' and 'small intestine.' It is concluded that the concept of electrodermal resistance at AP possesses criterion validity for distinguishing pain from a no pain state. This research provides support for the usefulness of measuring electrodermal activity when testing energy-based models of disease, and can be seen as a bridge between Western and Chinese medicine.

  19. 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

  20. 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…

  1. 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.

  2. 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.

  3. THE SECOND BLIND SPOT: SMALL RETINAL VESSEL VASCULOPATHY AFTER VACCINATION AGAINST NEISSERIA MENINGITIDIS AND YELLOW FEVER.

    Science.gov (United States)

    Moysidis, Stavros N; Koulisis, Nicole; Patel, Vivek R; Kashani, Amir H; Rao, Narsing A; Humayun, Mark S; Rodger, Damien C

    2017-01-01

    To describe a case of small retinal vessel vasculopathy postvaccination. We report the case of a 41-year-old white man who presented with a "second blind spot," describing a nasal scotoma in the right eye that started 4 days after vaccinations against Neisseria meningitidis and the yellow fever virus, and after a 2-month period of high stress and decreased sleep. Clinical examination, Humphrey visual field testing, and multimodal imaging with fundus photographs, autofluorescence, fluorescein angiography, and spectral domain optical coherence tomography and angiography were performed. Clinical examination revealed a well-circumscribed, triangular area of retinal graying of about 1-disk diameter in size, located at the border of the temporal macula. This corresponded to a deep scotoma similar in size to the physiologic blind spot on Humphrey visual field 24-2 testing. There was mild hypoautofluoresence of this lesion on autofluorescence, hypofluorescence on fluorescein angiography, and focal attenuation of a small artery just distal to the bifurcation of an artery supplying the involved area. Spectral domain optical coherence tomography through the lesion conveyed hyperreflectivity most prominent in the inner and outer plexiform layers, with extension of the hyperreflectivity into the ganglion cell and inner nuclear layers. Spectral domain optical coherence tomography angiography demonstrated arteriolar and capillary dropout, more pronounced in the superficial retinal layer compared to the deeper retinal layer. At 1-month follow-up, his scotoma improved with monitoring, with reduction from -32 dB to -7 dB on Humphrey visual field testing. There was clinical resolution of the area of graying and decreased hyperreflectivity on spectral domain optical coherence tomography, with atrophy of the inner retina. Spectral domain optical coherence tomography angiography showed progression of arteriolar and capillary dropout, more so in the superficial than in the deep capillary

  4. Asymptotic differentiation of signals in the trajectory tracking control of a differentially flat nonlinear magnetic suspension system

    OpenAIRE

    Francisco Beltrán Carbajal; Antonio Favela Contreras; Antonio Valderrábano González; Gerardo Silva Navarro

    2013-01-01

    En este artículo se aborda el problema de control para tareas de seguimiento de trayectorias de referencia variantes en el tiempo para la posición de un objeto en un sistema de levitación magnética no lineal diferencialmente plano, usando únicamente mediciones de posición. Se propone un esquema novedoso de diferenciación de señales para la estimación asintótica de la velocidad y aceleración. Este diferenciador de señales se puede utilizar en muchas aplicaciones de control de sistemas de inge...

  5. New proteoliposome vaccine formulation from N. meningitidis serogroup B, without aluminum hydroxide, retains its antimeningococcal protectogenic potential as well as Th-1 adjuvant capacity

    OpenAIRE

    Tamargo, Beatriz; Márquez, Yanet; Ramírez, Wendy; Cedré, Bárbara; Fresno, Manuel; Sierra, Gustavo

    2013-01-01

    Proteoliposomes purified from the Outer Membrane of Neisseria meningitidis B, have been successfully used as core for adjuvants and vaccine formulations. We have tried to increase their structural definition and to conserve their efficacy and stability avoiding the addition of the aluminum hydroxide to the final formulation. Liposomal particle systems were prepared from components of defined molecular structure, such as a Neisseria meningitidis B protein complex, extracted and purified withou...

  6. 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

  7. 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

  8. IL-4-Induced Gene 1: A Negative Immune Checkpoint Controlling B Cell Differentiation and Activation.

    Science.gov (United States)

    Bod, Lloyd; Douguet, Laetitia; Auffray, Cédric; Lengagne, Renée; Bekkat, Fériel; Rondeau, Elena; Molinier-Frenkel, Valérie; Castellano, Flavia; Richard, Yolande; Prévost-Blondel, Armelle

    2018-02-01

    Emerging data highlight the crucial role of enzymes involved in amino acid metabolism in immune cell biology. IL-4-induced gene-1 (IL4I1), a secreted l-phenylalanine oxidase expressed by APCs, has been detected in B cells, yet its immunoregulatory role has only been explored on T cells. In this study, we show that IL4I1 regulates multiple steps in B cell physiology. Indeed, IL4I1 knockout mice exhibit an accelerated B cell egress from the bone marrow, resulting in the accumulation of peripheral follicular B cells. They also present a higher serum level of natural Igs and self-reactive Abs. We also demonstrate that IL4I1 produced by B cells themselves controls the germinal center reaction, plasma cell differentiation, and specific Ab production in response to T dependent Ags, SRBC, and NP-KLH. In vitro, IL4I1-deficient B cells proliferate more efficiently than their wild-type counterparts in response to BCR cross-linking. Moreover, the absence of IL4I1 increases activation of the Syk-Akt-S6kinase signaling pathway and calcium mobilization, and inhibits SHP-1 activity upon BCR engagement, thus supporting that IL4I1 negatively controls BCR-dependent activation. Overall, our study reveals a new perspective on IL4I1 as a key regulator of B cell biology. Copyright © 2018 by The American Association of Immunologists, Inc.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Pneumonia caused by Neisseria meningitidis: report of a case and review of the literature

    International Nuclear Information System (INIS)

    Acosta M, Rafael E; Rada E, Robin A

    2010-01-01

    Pneumonia caused by Neisseria meningitidis, a gram-negative diplococcus affecting only humans, is a rare disease that was first recognized more than 60 years ago. The infection is usually manifested as meningitis and septicemia with cutaneous manifestations. Involvement of the lower respiratory tract is much less frequently diagnosed, partly because this microorganism can be present in the oropharyngeal flora of up to 10% of asymptomatic people. The serotypes most frequently involved in lung infections are: B, Y, and W-135. Serotype Y has been held to be most important. In cases of pneumonia, diagnosis has to be reached by isolation of the microorganism in blood and/or pleural fluid. Mortality is low, and person-to-person transmission, although documented, is rare. Complications such as pulmonary abscess, pleural effusion, and pericarditis are infrequent.

  14. Backbone resonance assignments of the outer membrane lipoprotein FrpD from Neisseria meningitidis.

    Science.gov (United States)

    Bumba, Ladislav; Sviridova, Ekaterina; Kutá Smatanová, Ivana; Řezáčová, Pavlína; Veverka, Václav

    2014-04-01

    The iron-regulated FrpD protein is a unique lipoprotein embedded into the outer membrane of the Gram-negative bacterium Neisseria meningitidis. The biological function of FrpD remains unknown but might consist in anchoring to the bacterial cell surface the Type I-secreted FrpC protein, which belongs to a Repeat in ToXins (RTX) protein family and binds FrpD with very high affinity (K(d) = 0.2 nM). Here, we report the backbone (1)H, (13)C, and (15)N chemical shift assignments for the FrpD(43-271) protein that allow us to characterize the intimate interaction between FrpD and the N-terminal domain of FrpC.

  15. Respuesta neuroinmunológica en niños con meningoencefalitis por Neisseria meningitidis

    Directory of Open Access Journals (Sweden)

    Bárbara Padilla-Docal

    2011-04-01

    Full Text Available La enfermedad meningocócica es una entidad clínica que constituye aún un problema de salud mundial. Esta afecta, sobre todo, a la población infantil ocasionando un cuadro clínico grave, de evolución severa, así como un elevado número de muertes y secuelas. Su agente etiológico, Neisseria meningitidis, habita de forma natural en las membranas mucosas de la nasofaringe humana. Con el objetivo de determinar las características de la respuesta neuroinmunológica en niños con meningoencefalitis por N. meningitidis, se estudiaron 20 niños diagnosticados con esta afección clínica, entre los años 1988- 2009. A estos se les realizó una punción lumbar en el momento del ingreso y se cuantificó la IgA, IgM e IgG, la albúmina y el C3c en el suero y en el líquido cefalorraquídeo. Se confeccionó un reibergrama de acuerdo con los datos obtenidos en la cuantificación. La disfunción de la barrera hematoencefálica se presentó en seis pacientes y hubo síntesis intratecal de las inmunoglobulinas mayores y C3c en 65% y 95%, respectivamente. Se comprobó la ocurrencia de síntesis intratecal de al menos dos inmunoglobulinas mayores asociadas con el componente C3c del complemento, participando estos en los mecanismos involucrados en la respuesta inmune de esta enfermedad.

  16. Use of restriction fragment length polymorphisms to investigate strain variation within Neisseria meningitidis

    International Nuclear Information System (INIS)

    Williams, S.D.

    1989-01-01

    Similarity within bacterial populations is difficult to assess due to the limited number of characters available for evaluation and the heterogeneity of bacterial species. Currently, the preferred method used to evaluate the structure of bacterial populations is multilocus enzyme electrophoresis. However, this method is extremely cumbersome and only offers an indirect measure of genetic similarities. The development of a more direct and less cumbersome method for this purpose is warranted. Restriction fragment length polymorphism analysis was evaluated as a tool for use in the study of bacterial population structures and in the epidemiology and surveillance of infectious disease. A collection of Neisseria meningitidis was available for use in the investigation of this technique. Neisseria meningitidis is the causative agent of epidemic cerebrospinal meningitis and septicemia as well as a variety of other clinical manifestations. Each isolate in the collection was defined in terms of serogroup specificity, clinical history, geographic source, and date of isolation. Forty-six strains were chosen for this study. The DNA from each strain was restricted with Pst1 and EcoR1 and electrophoresed on agarose gels. The DNA was transferred to nylon filters and hybridized with P 32 labeled DNA probes. Two randomly generated probes and a gene-specific probe were used to estimate the genetic similarities between and among the strains in the study population. A total of 28 different restriction fragment migration types were detected by the probes used. Data obtained from the RFLP analysis was analyzed by cluster analysis and multivariate statistical methods. A total of 7 clones groups were detected. Two of these appear to be major clones that comprise 35% of the population

  17. Use of restriction fragment length polymorphisms to investigate strain variation within Neisseria meningitidis

    Energy Technology Data Exchange (ETDEWEB)

    Williams, S.D.

    1989-01-01

    Similarity within bacterial populations is difficult to assess due to the limited number of characters available for evaluation and the heterogeneity of bacterial species. Currently, the preferred method used to evaluate the structure of bacterial populations is multilocus enzyme electrophoresis. However, this method is extremely cumbersome and only offers an indirect measure of genetic similarities. The development of a more direct and less cumbersome method for this purpose is warranted. Restriction fragment length polymorphism analysis was evaluated as a tool for use in the study of bacterial population structures and in the epidemiology and surveillance of infectious disease. A collection of Neisseria meningitidis was available for use in the investigation of this technique. Neisseria meningitidis is the causative agent of epidemic cerebrospinal meningitis and septicemia as well as a variety of other clinical manifestations. Each isolate in the collection was defined in terms of serogroup specificity, clinical history, geographic source, and date of isolation. Forty-six strains were chosen for this study. The DNA from each strain was restricted with Pst1 and EcoR1 and electrophoresed on agarose gels. The DNA was transferred to nylon filters and hybridized with P{sup 32} labeled DNA probes. Two randomly generated probes and a gene-specific probe were used to estimate the genetic similarities between and among the strains in the study population. A total of 28 different restriction fragment migration types were detected by the probes used. Data obtained from the RFLP analysis was analyzed by cluster analysis and multivariate statistical methods. A total of 7 clones groups were detected. Two of these appear to be major clones that comprise 35% of the population.

  18. Meningitis Dipstick Rapid Test: Evaluating Diagnostic Performance during an Urban Neisseria meningitidis Serogroup A Outbreak, Burkina Faso, 2007

    Science.gov (United States)

    Rose, Angela M. C.; Mueller, Judith E.; Gerstl, Sibylle; Njanpop-Lafourcade, Berthe-Marie; Page, Anne-Laure; Nicolas, Pierre; Traoré, Ramata Ouédraogo; Caugant, Dominique A.; Guerin, Philippe J.

    2010-01-01

    Meningococcal meningitis outbreaks occur every year during the dry season in the “meningitis belt” of sub-Saharan Africa. Identification of the causative strain is crucial before launching mass vaccination campaigns, to assure use of the correct vaccine. Rapid agglutination (latex) tests are most commonly available in district-level laboratories at the beginning of the epidemic season; limitations include a short shelf-life and the need for refrigeration and good technical skills. Recently, a new dipstick rapid diagnostic test (RDT) was developed to identify and differentiate disease caused by meningococcal serogroups A, W135, C and Y. We evaluated the diagnostic performance of this dipstick RDT during an urban outbreak of meningitis caused by N. meningitidis serogroup A in Ouagadougou, Burkina Faso; first against an in-country reference standard of culture and/or multiplex PCR; and second against culture and/or a highly sensitive nested PCR technique performed in Oslo, Norway. We included 267 patients with suspected acute bacterial meningitis. Using the in-country reference standard, 50 samples (19%) were positive. Dipstick RDT sensitivity (N = 265) was 70% (95%CI 55–82) and specificity 97% (95%CI 93–99). Using culture and/or nested PCR, 126/259 (49%) samples were positive; dipstick RDT sensitivity (N = 257) was 32% (95%CI 24–41), and specificity was 99% (95%CI 95–100). We found dipstick RDT sensitivity lower than values reported from (i) assessments under ideal laboratory conditions (>90%), and (ii) a prior field evaluation in Niger [89% (95%CI 80–95)]. Specificity, however, was similar to (i), and higher than (ii) [62% (95%CI 48–75)]. At this stage in development, therefore, other tests (e.g., latex) might be preferred for use in peripheral health centres. We highlight the value of field evaluations for new diagnostic tests, and note relatively low sensitivity of a reference standard using multiplex vs. nested PCR. Although the former is

  19. Meningitis dipstick rapid test: evaluating diagnostic performance during an urban Neisseria meningitidis serogroup A outbreak, Burkina Faso, 2007.

    Directory of Open Access Journals (Sweden)

    Angela M C Rose

    Full Text Available Meningococcal meningitis outbreaks occur every year during the dry season in the "meningitis belt" of sub-Saharan Africa. Identification of the causative strain is crucial before launching mass vaccination campaigns, to assure use of the correct vaccine. Rapid agglutination (latex tests are most commonly available in district-level laboratories at the beginning of the epidemic season; limitations include a short shelf-life and the need for refrigeration and good technical skills. Recently, a new dipstick rapid diagnostic test (RDT was developed to identify and differentiate disease caused by meningococcal serogroups A, W135, C and Y. We evaluated the diagnostic performance of this dipstick RDT during an urban outbreak of meningitis caused by N. meningitidis serogroup A in Ouagadougou, Burkina Faso; first against an in-country reference standard of culture and/or multiplex PCR; and second against culture and/or a highly sensitive nested PCR technique performed in Oslo, Norway. We included 267 patients with suspected acute bacterial meningitis. Using the in-country reference standard, 50 samples (19% were positive. Dipstick RDT sensitivity (N = 265 was 70% (95%CI 55-82 and specificity 97% (95%CI 93-99. Using culture and/or nested PCR, 126/259 (49% samples were positive; dipstick RDT sensitivity (N = 257 was 32% (95%CI 24-41, and specificity was 99% (95%CI 95-100. We found dipstick RDT sensitivity lower than values reported from (i assessments under ideal laboratory conditions (>90%, and (ii a prior field evaluation in Niger [89% (95%CI 80-95]. Specificity, however, was similar to (i, and higher than (ii [62% (95%CI 48-75]. At this stage in development, therefore, other tests (e.g., latex might be preferred for use in peripheral health centres. We highlight the value of field evaluations for new diagnostic tests, and note relatively low sensitivity of a reference standard using multiplex vs. nested PCR. Although the former is the current standard

  20. 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.

  1. Quaking promotes monocyte differentiation into pro-atherogenic macrophages by controlling pre-mRNA splicing and gene expression.

    Science.gov (United States)

    de Bruin, Ruben G; Shiue, Lily; Prins, Jurriën; de Boer, Hetty C; Singh, Anjana; Fagg, W Samuel; van Gils, Janine M; Duijs, Jacques M G J; Katzman, Sol; Kraaijeveld, Adriaan O; Böhringer, Stefan; Leung, Wai Y; Kielbasa, Szymon M; Donahue, John P; van der Zande, Patrick H J; Sijbom, Rick; van Alem, Carla M A; Bot, Ilze; van Kooten, Cees; Jukema, J Wouter; Van Esch, Hilde; Rabelink, Ton J; Kazan, Hilal; Biessen, Erik A L; Ares, Manuel; van Zonneveld, Anton Jan; van der Veer, Eric P

    2016-03-31

    A hallmark of inflammatory diseases is the excessive recruitment and influx of monocytes to sites of tissue damage and their ensuing differentiation into macrophages. Numerous stimuli are known to induce transcriptional changes associated with macrophage phenotype, but posttranscriptional control of human macrophage differentiation is less well understood. Here we show that expression levels of the RNA-binding protein Quaking (QKI) are low in monocytes and early human atherosclerotic lesions, but are abundant in macrophages of advanced plaques. Depletion of QKI protein impairs monocyte adhesion, migration, differentiation into macrophages and foam cell formation in vitro and in vivo. RNA-seq and microarray analysis of human monocyte and macrophage transcriptomes, including those of a unique QKI haploinsufficient patient, reveal striking changes in QKI-dependent messenger RNA levels and splicing of RNA transcripts. The biological importance of these transcripts and requirement for QKI during differentiation illustrates a central role for QKI in posttranscriptionally guiding macrophage identity and function.

  2. Quaking promotes monocyte differentiation into pro-atherogenic macrophages by controlling pre-mRNA splicing and gene expression

    Science.gov (United States)

    de Bruin, Ruben G.; Shiue, Lily; Prins, Jurriën; de Boer, Hetty C.; Singh, Anjana; Fagg, W. Samuel; van Gils, Janine M.; Duijs, Jacques M. G. J.; Katzman, Sol; Kraaijeveld, Adriaan O.; Böhringer, Stefan; Leung, Wai Y.; Kielbasa, Szymon M.; Donahue, John P.; van der Zande, Patrick H.J.; Sijbom, Rick; van Alem, Carla M. A.; Bot, Ilze; van Kooten, Cees; Jukema, J. Wouter; Van Esch, Hilde; Rabelink, Ton J.; Kazan, Hilal; Biessen, Erik A. L.; Ares Jr., Manuel; van Zonneveld, Anton Jan; van der Veer, Eric P.

    2016-01-01

    A hallmark of inflammatory diseases is the excessive recruitment and influx of monocytes to sites of tissue damage and their ensuing differentiation into macrophages. Numerous stimuli are known to induce transcriptional changes associated with macrophage phenotype, but posttranscriptional control of human macrophage differentiation is less well understood. Here we show that expression levels of the RNA-binding protein Quaking (QKI) are low in monocytes and early human atherosclerotic lesions, but are abundant in macrophages of advanced plaques. Depletion of QKI protein impairs monocyte adhesion, migration, differentiation into macrophages and foam cell formation in vitro and in vivo. RNA-seq and microarray analysis of human monocyte and macrophage transcriptomes, including those of a unique QKI haploinsufficient patient, reveal striking changes in QKI-dependent messenger RNA levels and splicing of RNA transcripts. The biological importance of these transcripts and requirement for QKI during differentiation illustrates a central role for QKI in posttranscriptionally guiding macrophage identity and function. PMID:27029405

  3. Differential-Evolution Control Parameter Optimization for Unmanned Aerial Vehicle Path Planning.

    Science.gov (United States)

    Kok, Kai Yit; Rajendran, Parvathy

    2016-01-01

    The differential evolution algorithm has been widely applied on unmanned aerial vehicle (UAV) path planning. At present, four random tuning parameters exist for differential evolution algorithm, namely, population size, differential weight, crossover, and generation number. These tuning parameters are required, together with user setting on path and computational cost weightage. However, the optimum settings of these tuning parameters vary according to application. Instead of trial and error, this paper presents an optimization method of differential evolution algorithm for tuning the parameters of UAV path planning. The parameters that this research focuses on are population size, differential weight, crossover, and generation number. The developed algorithm enables the user to simply define the weightage desired between the path and computational cost to converge with the minimum generation required based on user requirement. In conclusion, the proposed optimization of tuning parameters in differential evolution algorithm for UAV path planning expedites and improves the final output path and computational cost.

  4. Structure of the cold-shock domain protein from Neisseria meningitidis reveals a strand-exchanged dimer

    Energy Technology Data Exchange (ETDEWEB)

    Ren, Jingshan [The Oxford Protein Production Facility, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Division of Structural Biology, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Nettleship, Joanne E.; Sainsbury, Sarah [The Oxford Protein Production Facility, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Saunders, Nigel J. [Bacterial Pathogenesis and Functional Genomics Group, Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE (United Kingdom); Owens, Raymond J., E-mail: ray@strubi.ox.ac.uk [The Oxford Protein Production Facility, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom)

    2008-04-01

    The X-ray crystal structure of the cold-shock domain protein from N. meningitidis reveals a strand-exchanged dimer. The structure of the cold-shock domain protein from Neisseria meningitidis has been solved to 2.6 Å resolution and shown to comprise a dimer formed by the exchange of two β-strands between protein monomers. The overall fold of the monomer closely resembles those of other bacterial cold-shock proteins. The neisserial protein behaved as a monomer in solution and was shown to bind to a hexathymidine oligonucleotide with a stoichiometry of 1:1 and a K{sub d} of 1.25 µM.

  5. 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.

  6. 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.

  7. 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.

  8. Increase of Neisseria meningitidis W:cc11 invasive disease in Chile has no correlation with carriage in adolescents.

    Directory of Open Access Journals (Sweden)

    Paulina S Rubilar

    Full Text Available Neisseria meningitidis is a human exclusive pathogen that can lead to invasive meningococcal disease or may be carried in the upper respiratory tract without symptoms. The relationship between carriage and disease remains poorly understood but it is widely accepted that decreasing carriage by immunization should lead to a reduction of invasive cases. Latin America has experienced an increased incidence of serogroup W invasive cases of Neisseria meningitidis in the last decade. Specifically in Chile, despite low total incidence of invasive cases, serogroup W has become predominant since 2011 and has been associated with elevated mortality. Expecting to gain insight into the epidemiology of this disease, this study has used molecular typing schemes to compare Neisseria meningitidis isolates causing invasive disease with those isolates collected from adolescent carriers during the same period in Chile. A lower carriage of the serogroup W clonal complex ST-11/ET37 than expected was found; whereas, the same clonal complex accounted for 66% of total invasive meningococcal disease cases in the country that year. A high diversity of PorA variable regions and fHbp peptides was also ascertained in the carrier isolates compared to the invasive ones. According to the results shown here, the elevated number of serogroup W invasive cases in our country cannot be explained by a rise of carriage of pathogenic isolates. Overall, this study supports the idea that some strains, as W:cc11 found in Chile, possess an enhanced virulence to invade the host. Notwithstanding hypervirulence, this strain has not caused an epidemic in Chile. Finally, as genetic transfer occurs often, close surveillance of Neisseria meningitidis strains causing disease, and particularly hypervirulent W:cc11, should be kept as a priority in our country, in order to prepare the best response to face genetic changes that could lead to enhanced fitness of this pathogen.

  9. Crystal structure of the iron-regulated outer membrane lipoprotein FrpD (NMB0584) from Neisseria meningitidis

    Czech Academy of Sciences Publication Activity Database

    Sviridova, E.; Bumba, Ladislav; Řezáčová, Pavlína; Šebo, Peter; Kutá-Smatanová, Ivana

    2012-01-01

    Roč. 12, č. 1 (2012), s. 49-49 ISSN 1210-8529. [10th Discussions in Structural Molecular Biology. 22.03.2012-24.03.2012, Nové Hrady] R&D Projects: GA ČR(CZ) GAP207/11/0717 Institutional research plan: CEZ:AV0Z40550506; CEZ:AV0Z60870520; CEZ:AV0Z50200510 Keywords : Neisseria meningitidis * FrpD Subject RIV: EE - Microbiology, Virology

  10. Polysaccharide production in batch process of Neisseria meningitidis serogroup C comparing Frantz, modified Frantz and Cartlin 6 cultivation media

    OpenAIRE

    Paz Marcelo Fossa da; Baruque-Ramos Júlia; Hiss Haroldo; Vicentin Márcio Alberto; Leal Maria Betania Batista; Raw Isaías

    2003-01-01

    Polysaccharide of N. meningitidis serogroup C constitutes the antigen for the vaccine against meningitis. The goal of this work was to compare three cultivation media for production of this polysaccharide: Frantz, modified Frantz medium (with replacement of glucose by glycerol), and Catlin 6 (a synthetic medium with glucose). The comparative criteria were based on the final polysaccharide concentrations and the yield coefficient cell/polysaccharide (Y P/X). The kinetic parameters: pH, substra...

  11. 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.

  12. 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.

  13. Liposomes or traditional adjuvants: induction of bactericidal activity by the macrophage infectivity potentiator protein (Mip) of Neisseria meningitidis.

    Science.gov (United States)

    Costoya, Liliana; Marzoa, Juan; Ferreirós, Carlos; Criado, Maria Teresa

    2017-08-01

    Currently, one of the main approaches to achieve a vaccine for serogroup B Neisseria meningitidis is based on outer membrane proteins with low antigenic variability among strains. Since these proteins tend to be minor components of the outer membrane, recombinant production is required to obtain them in sufficient amounts for evaluation and development of vaccines. In this study, we analysed the ability of recombinant macrophage infectivity potentiator (rMip) protein to induce protective bactericidal activity in mice. The rMip protein was cloned from N. meningitidis strain H44/76 and was used to immunise mice, and the sera obtained were tested against the homologous and several heterologous N. meningitidis strains. The sera were obtained using the rMip alone, with adjuvant Al(OH) 3 , or after inclusion into liposomes. Bactericidal activity was variable depending on the strain, although high titres were seen against strains H44/76 and NmP27. Liposomes enhanced fourfold the reactivity against the homologous strain. The results presented suggest that the rMip protein should be considered a promising candidate for the improvement of future protein-based vaccines. © 2017 APMIS. Published by John Wiley & Sons Ltd.

  14. Construction of Opa-positive and Opa-negative strains of Neisseria meningitidis to evaluate a novel meningococcal vaccine.

    Science.gov (United States)

    Sadarangani, Manish; Hoe, J Claire; Callaghan, Martin J; Jones, Claire; Chan, Hannah; Makepeace, Katherine; Daniels-Treffandier, Hélène; Deadman, Mary E; Bayliss, Christopher; Feavers, Ian; van der Ley, Peter; Pollard, Andrew J

    2012-01-01

    Neisseria meningitidis is a major global pathogen causing invasive disease with a mortality of 5-10%. Most disease in developed countries is caused by serogroup B infection, against which there is no universal vaccine. Opacity-associated adhesin (Opa) proteins are major meningococcal outer membrane proteins, which have shown recent promise as a potential novel vaccine. Immunisation of mice with different Opa variants elicited high levels of meningococcal-specific bactericidal antibodies, demonstrating proof in principle for this approach. Opa proteins are critical in meningococcal pathogenesis, mediating bacterial adherence to host cells, and modulating human cellular immunity via interactions with T cells and neutrophils, although there are conflicting data regarding their effects on CD4(+) T cells. We constructed Opa-positive and Opa-negative meningococcal strains to allow further evaluation of Opa as a vaccine component. All four opa genes from N. meningitidis strain H44/76 were sequentially disrupted to construct all possible combinations of N. meningitidis strains deficient in one, two, three, or all four opa genes. The transformations demonstrated that homologous recombination of exogenous DNA into the meningococcal chromosome can occur with as little as 80 bp, and that minor sequence differences are permissible. Anti-Opa bactericidal antibody responses following immunisation of mice with recombinant Opa were specific to the Opa variant used in immunisation. No immunomodulatory effects were observed when Opa was contained within meningococcal outer membrane vesicles (OMVs), compared to Opa-negative OMVs. These observations support the incorporation of Opa in meningococcal vaccines.

  15. Preliminary crystallographic data of the three homologues of the thiol–disulfide oxidoreductase DsbA in Neisseria meningitidis

    Energy Technology Data Exchange (ETDEWEB)

    Lafaye, Céline [Laboratoire des Protéines Membranaires, Institut de Biologie Structurale, CEA/CNRS/Université Joseph Fourier, 41 Rue Jules Horowitz, 38027 Grenoble CEDEX 01 (France); Iwena, Thomas; Ferrer, Jean-Luc [Laboratoire de Cristallogénèse et Cristallisation des Protéines, Institut de Biologie Structurale, CEA/CNRS/Université Joseph Fourier, 41 Rue Jules Horowitz, 38027 Grenoble CEDEX 01 (France); Kroll, J. Simon [Department of Paediatrics, Imperial College London, St Mary’s Hospital Campus, Norfolk Place, London W2 1PG (United Kingdom); Griat, Mickael; Serre, Laurence, E-mail: laurence.serre@ibs.fr [Laboratoire des Protéines Membranaires, Institut de Biologie Structurale, CEA/CNRS/Université Joseph Fourier, 41 Rue Jules Horowitz, 38027 Grenoble CEDEX 01 (France)

    2008-02-01

    The Neisseria meningitidis genome possesses three genes encoding active DsbAs. To throw light on the reason for this genetic multiplicity, the three enzymes have been purified and crystallized. Bacterial virulence depends on the correct folding of surface-exposed proteins, a process that is catalyzed by the thiol-disulfide oxidoreductase DsbA, which facilitates the synthesis of disulfide bonds in Gram-negative bacteria. Uniquely among bacteria, the Neisseria meningitidis genome possesses three genes encoding active DsbAs: DsbA1, DsbA2 and DsbA3. DsbA1 and DsbA2 have been characterized as lipoproteins involved in natural competence and in host-interactive biology, while the function of DsbA3 remains unknown. In an attempt to shed light on the reason for this multiplicity of dsbA genes, the three enzymes from N. meningitidis have been purified and crystallized in the presence of high concentrations of ammonium sulfate. The best crystals were obtained using DsbA1 and DsbA3; they belong to the orthorhombic and tetragonal systems and diffract to 1.5 and 2.7 Å resolution, respectively.

  16. 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 ).

  17. 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.

  18. 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.

  19. Can the Children's Communication Checklist differentiate between children with autism, children with ADHD, and normal controls?

    Science.gov (United States)

    Geurts, Hilde M; Verté, Sylvie; Oosterlaan, Jaap; Roeyers, Herbert; Hartman, Catharina A; Mulder, Erik J; Berckelaer-Onnes, Ina A; Sergeant, Joseph A

    2004-11-01

    The Children's Communication Checklist (CCC; Bishop, 1998) is a questionnaire that was developed to measure pragmatic language use and may be completed by parents and teachers. Two studies are reported, which were designed to investigate: (1) whether children with Attention Deficit Hyperactivity Disorder (ADHD) encounter pragmatic language problems in comparison with normal controls (NC), (2) whether children with ADHD and children with High Functioning Autism (HFA) can be differentiated using the CCC, (3) the usefulness of the CCC for parents and teachers in a clinical and in a research setting, and (4) the role of age in pragmatic language use in ADHD and HFA. In the first study (clinical sample) 50 children with ADHD, 50 children with HFA, and 50 NC were compared to each other using the CCC. In the second study (research sample) CCC data was gathered on 23 children with ADHD (without co-morbid disorders), 42 children with HFA, and 35 NC. Compared to NC, children with HFA showed pragmatic deficits on all CCC scales. Children with ADHD demonstrated deficits compared to NC as well. Moreover, the ADHD and HFA groups differed from each other on most of the scales. Discriminant analyses showed that CCC scales were relevant for case identification in these samples. Furthermore, profiles of impairment seen in children with HFA and ADHD did not vary with age. Pragmatic difficulties do occur in both HFA and ADHD. The present studies indicate that the CCC is a useful instrument to obtain information concerning pragmatic language use in both a clinical and a research setting. Although the information of parents is more tightly linked to the diagnosis, combining the information of both parent and teacher slightly improves case identification.

  20. Optimization of Molecular Approaches to Genogroup Neisseria meningitidis Carriage Isolates and Implications for Monitoring the Impact of New Serogroup B Vaccines.

    Directory of Open Access Journals (Sweden)

    Eduardo Rojas

    Full Text Available The reservoir for Neisseria meningitidis (Nm is the human oropharynx. Implementation of Nm serogroup C (NmC glycoconjugate vaccines directly reduced NmC carriage. Prophylactic vaccines are now available to prevent disease caused by the five major Nm disease causing serogroups (ABCWY. Nm serogroup B (NmB vaccines are composed of antigens that are conserved across Nm serogroups and therefore have the potential to impact all Nm carriage. To assess the effect of these vaccines on carriage, standardized approaches to identify and group Nm are required. Real-time PCR (rt-PCR capsule grouping assays that were internally controlled to confirm Nm species were developed for eight serogroups associated with carriage (A, B, C, E, W, X, Y and Z. The grouping scheme was validated using diverse bacterial species associated with carriage and then used to evaluate a collection of diverse Nm carriage isolates (n=234. A scheme that also included porA and ctrA probes was able to speciate the isolates, while ctrA also provided insights on the integrity of the polysaccharide loci. Isolates were typed for the Nm vaccine antigen factor H binding protein (fHbp, and were found to represent the known diversity of this antigen. The porA rt-PCR yielded positive results with all 234 of the Nm carriage isolates. Genogrouping assays classified 76.5% (179/234 of these isolates to a group, categorized 53 as nongenogroupable (NGG and two as mixed results. Thirty seven NGG isolates evidenced a disrupted capsular polysaccharide operon judged by a ctrA negative result. Only 28.6% (67/234 of the isolates were serogrouped by slide agglutination (SASG, highlighting the reduced capability of carriage strains to express capsular polysaccharide. These rt-PCR assays provide a comprehensive means to identify and genogroup N. meningitidis in carriage studies used to guide vaccination strategies and to assess the impact of novel fHbp containing vaccines on meningococcal carriage.

  1. Molecular epidemiology and emergence of worldwide epidemic clones of Neisseria meningitidis in Taiwan

    Directory of Open Access Journals (Sweden)

    Chang Hsiu-Li

    2006-02-01

    Full Text Available Abstract Background Meningococcal disease is infrequently found in Taiwan, a country with 23 million people. Between 1996 and 2002, 17 to 81 clinical cases of the disease were reported annually. Reported cases dramatically increased in 2001–2002. Our record shows that only serogroup B and W135 meningococci have been isolated from patients with meningococcal disease until 2000. However, serogroup A, C and Y meningococci were detected for the first time in 2001 and continued to cause disease through 2002. Most of serogroup Y meningococcus infections localized in Central Taiwan in 2001, indicating that a small-scale outbreak of meningococcal disease had occurred. The occurrence of a meningococcal disease outbreak and the emergence of new meningococcal strains are of public health concern. Methods Neisseria meningitidis isolates from patients with meningococcal disease from 1996 to 2002 were collected and characterized by serogrouping, pulsed-field gel electrophoresis (PFGE and multilocus sequence typing (MLST. The genetic relatedness and clonal relationship between the isolates were analyzed by using the PFGE patterns and the allelic profiles of the sequence types (STs. Results Serogroups A, B, C, W135, Y, and non-serogroupable Neisseria meningitidis were, respectively, responsible for 2%, 50%, 2%, 35%, 9%, and 2% of 158 culture-confirmed cases of meningococcal disease in 1996–2002. Among 100 N. meningitidis isolates available for PFGE and MLST analyses, 51 different PFGE patterns and 30 STs were identified with discriminatory indices of 0.95 and 0.87, respectively. Of the 30 STs, 21 were newly identified and of which 19 were found in serogroup B isolates. A total of 40 PFGE patterns were identified in 52 serogroup B isolates with the patterns distributed over several distinct clusters. In contrast, the isolates within each of the serogroups A, C, W135, and Y shared high levels of PFGE pattern similarity. Analysis of the allelic profile of the

  2. 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.

  3. Does Syndrome Differentiation Matter? A Meta-Analysis of Randomized Controlled Trials in Cochrane Reviews of Acupuncture.

    Science.gov (United States)

    Cao, Huijuan; Bourchier, Suzannah; Liu, Jianping

    2012-06-01

    One of the basic and important principles of Traditional Chinese Medicine theory is syndrome differentiation, which is widely utilized for individual diagnosis and in the application of acupuncture treatment. However, the impact of syndrome differentiation on therapeutic effect is unclear because of insufficient supportive clinical evidence. The aim of this study was to analyze current Cochrane Database systematic reviews of acupuncture and to evaluate differences in therapeutic effects of acupuncture treatment when syndrome differentiation is utilized, compared to when this approach is not utilized. Cochrane Database systematic reviews of acupuncture were included if the reviews had sufficient data to perform subgroup analyses by syndrome differentiation applied during acupoints' selection. Searching was conducted across all available articles of the Cochrane Library, and the search concluded in July 2011. Forty-four trials from five Cochrane reviews were included in 10 subgroup meta-analyses. Seven meta-analyses showed that there were no differences between trials using fixed acupoints prescriptions and trials using individualized treatment based on relevant symptom improvements in cases of acute stroke, depression, epilepsy, migraine, and peripheral joint osteoarthritis (OA). The remaining 3 meta-analyses showed that acupuncture with fixed prescriptions was superior to individualized acupuncture for pain relief of peripheral joint OA, compared to sham control. The available evidence showed no significant difference between acupuncture treatment with or without syndrome differentiation. Large, well-designed trials are warranted to address the use of syndrome differentiation for specific diseases or conditions in order to confirm if there are any advantages of using syndrome differentiation to achieve better therapeutic effects with acupuncture.

  4. The Hippo pathway controls a switch between retinal progenitor cell proliferation and photoreceptor cell differentiation in zebrafish.

    Directory of Open Access Journals (Sweden)

    Yoichi Asaoka

    Full Text Available The precise regulation of numbers and types of neurons through control of cell cycle exit and terminal differentiation is an essential aspect of neurogenesis. The Hippo signaling pathway has recently been identified as playing a crucial role in promoting cell cycle exit and terminal differentiation in multiple types of stem cells, including in retinal progenitor cells. When Hippo signaling is activated, the core Mst1/2 kinases activate the Lats1/2 kinases, which in turn phosphorylate and inhibit the transcriptional cofactor Yap. During mouse retinogenesis, overexpression of Yap prolongs progenitor cell proliferation, whereas inhibition of Yap decreases this proliferation and promotes retinal cell differentiation. However, to date, it remains unknown how the Hippo pathway affects the differentiation of distinct neuronal cell types such as photoreceptor cells. In this study, we investigated whether Hippo signaling regulates retinogenesis during early zebrafish development. Knockdown of zebrafish mst2 induced early embryonic defects, including altered retinal pigmentation and morphogenesis. Similar abnormal retinal phenotypes were observed in zebrafish embryos injected with a constitutively active form of yap [(yap (5SA]. Loss of Yap's TEAD-binding domain, two WW domains, or transcription activation domain attenuated the retinal abnormalities induced by yap (5SA, indicating that all of these domains contribute to normal retinal development. Remarkably, yap (5SA-expressing zebrafish embryos displayed decreased expression of transcription factors such as otx5 and crx, which orchestrate photoreceptor cell differentiation by activating the expression of rhodopsin and other photoreceptor cell genes. Co-immunoprecipitation experiments revealed that Rx1 is a novel interacting partner of Yap that regulates photoreceptor cell differentiation. Our results suggest that Yap suppresses the differentiation of photoreceptor cells from retinal progenitor cells by

  5. Transcriptome analysis of Neisseria meningitidis in human whole blood and mutagenesis studies identify virulence factors involved in blood survival.

    Directory of Open Access Journals (Sweden)

    Hebert Echenique-Rivera

    2011-05-01

    Full Text Available During infection Neisseria meningitidis (Nm encounters multiple environments within the host, which makes rapid adaptation a crucial factor for meningococcal survival. Despite the importance of invasion into the bloodstream in the meningococcal disease process, little is known about how Nm adapts to permit survival and growth in blood. To address this, we performed a time-course transcriptome analysis using an ex vivo model of human whole blood infection. We observed that Nm alters the expression of ≈30% of ORFs of the genome and major dynamic changes were observed in the expression of transcriptional regulators, transport and binding proteins, energy metabolism, and surface-exposed virulence factors. In particular, we found that the gene encoding the regulator Fur, as well as all genes encoding iron uptake systems, were significantly up-regulated. Analysis of regulated genes encoding for surface-exposed proteins involved in Nm pathogenesis allowed us to better understand mechanisms used to circumvent host defenses. During blood infection, Nm activates genes encoding for the factor H binding proteins, fHbp and NspA, genes encoding for detoxifying enzymes such as SodC, Kat and AniA, as well as several less characterized surface-exposed proteins that might have a role in blood survival. Through mutagenesis studies of a subset of up-regulated genes we were able to identify new proteins important for survival in human blood and also to identify additional roles of previously known virulence factors in aiding survival in blood. Nm mutant strains lacking the genes encoding the hypothetical protein NMB1483 and the surface-exposed proteins NalP, Mip and NspA, the Fur regulator, the transferrin binding protein TbpB, and the L-lactate permease LctP were sensitive to killing by human blood. This increased knowledge of how Nm responds to adaptation in blood could also be helpful to develop diagnostic and therapeutic strategies to control the devastating

  6. 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.

  7. Knowledge, attitudes and behaviors of the Italian population towards Neisseria meningitidis, Streptococcus pneumoniae and HPV diseases and vaccinations: A cross-sectional multicentre study.

    Science.gov (United States)

    de Waure, C; Quaranta, G; Ianuale, C; Panatto, D; Amicizia, D; Apprato, L; Campanella, P; Colotto, M; De Meo, C; Di Nardo, F; Frisicale, E M; La Milia, D I; Rizzitelli, E; Aquilani, S; Briata, M P; Frumento, V; Marensi, L; Spadea, A; Turello, V; Gasparini, R; Ricciardi, W

    2016-12-01

    This study addressed knowledge of Streptococcus pneumoniae, Neisseria meningitidis and human papillomavirus (HPV), and attitudes and behaviours towards vaccines against them. This is a cross-sectional, multicentre study. Data were collected through a questionnaire administered to 530 adults who accessed four Departments of Prevention of the Italian National Health Service in 2013. Less than 50% of people gave the right answer to all the questions concerning the three diseases, but 96.2%, 94% and 92.7% agreed with the importance of vaccination against N. meningitidis, S. pneumoniae and HPV, respectively, and 58.4% expressed own willingness to have their children vaccinated with N. meningitidis B vaccine. The attitude towards vaccination was more positive in women for N. meningitidis and in people having children for HPV. Furthermore, individuals giving correct answers to all knowledge items were more in favour of both HPV and S. pneumoniae vaccination. A total of 68.8%, 82.6% and 84.5% of respondents vaccinated their own children against N. meningitidis C, S. pneumoniae and HPV, respectively. About 50% of the respondents reported paediatricians' or other health professionals' recommendations as the main reason for vaccination. Vaccinations may be promoted through actions aimed at increasing citizens' knowledge. Health professionals should be educated to actively provide information on vaccinations in a clear, comprehensive and effective way. Copyright © 2016 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.

  8. 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.

  9. 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.

  10. 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

  11. CARMEN, a human super enhancer-associated long noncoding RNA controlling cardiac specification, differentiation and homeostasis.

    Science.gov (United States)

    Ounzain, Samir; Micheletti, Rudi; Arnan, Carme; Plaisance, Isabelle; Cecchi, Dario; Schroen, Blanche; Reverter, Ferran; Alexanian, Michael; Gonzales, Christine; Ng, Shi Yan; Bussotti, Giovanni; Pezzuto, Iole; Notredame, Cedric; Heymans, Stephane; Guigó, Roderic; Johnson, Rory; Pedrazzini, Thierry

    2015-12-01

    Long noncoding RNAs (lncRNAs) are emerging as important regulators of developmental pathways. However, their roles in human cardiac precursor cell (CPC) remain unexplored. To characterize the long noncoding transcriptome during human CPC cardiac differentiation, we profiled the lncRNA transcriptome in CPCs isolated from the human fetal heart and identified 570 lncRNAs that were modulated during cardiac differentiation. Many of these were associated with active cardiac enhancer and super enhancers (SE) with their expression being correlated with proximal cardiac genes. One of the most upregulated lncRNAs was a SE-associated lncRNA that was named CARMEN, (CAR)diac (M)esoderm (E)nhancer-associated (N)oncoding RNA. CARMEN exhibits RNA-dependent enhancing activity and is upstream of the cardiac mesoderm-specifying gene regulatory network. Interestingly, CARMEN interacts with SUZ12 and EZH2, two components of the polycomb repressive complex 2 (PRC2). We demonstrate that CARMEN knockdown inhibits cardiac specification and differentiation in cardiac precursor cells independently of MIR-143 and -145 expression, two microRNAs located proximal to the enhancer sequences. Importantly, CARMEN expression was activated during pathological remodeling in the mouse and human hearts, and was necessary for maintaining cardiac identity in differentiated cardiomyocytes. This study demonstrates therefore that CARMEN is a crucial regulator of cardiac cell differentiation and homeostasis. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. A comparison of the endotoxin biosynthesis and protein oxidation pathways in the biogenesis of the outer membrane of Escherichia coli and Neisseria meningitidis

    Directory of Open Access Journals (Sweden)

    Susannah ePiek

    2012-12-01

    Full Text Available The Gram-negative bacterial cell envelope consists of an inner membrane (IM that surrounds the cytoplasm, and an asymmetrical outer-membrane (OM that forms a protective barrier to the external environment. The OM consists of lipopolysaccahride (LPS, phospholipids, outer membrane proteins (OMPs and lipoproteins. Oxidative protein folding mediated by periplasmic oxidoreductases is required for the correct biogenesis of the protein components, mainly constituents of virulence determinants such as pili, flagella and toxins, of the Gram-negative OM. Recently, periplasmic oxidoreductases have been implicated in LPS biogenesis of Escherichia coli and Neisseria meningitidis. Differences in OM biogenesis, in particular the transport pathways for endotoxin to the OM, the composition and role of the protein oxidation and isomerisation pathways and the regulatory networks that control them have been found in these two Gram-negative species suggesting that although form and function of the OM is conserved, these conserved pathways have been modified to suit the lifestyle of each organism.

  13. Snail regulates BMP and TGFβ pathways to control the differentiation status of glioma-initiating cells.

    Science.gov (United States)

    Caja, Laia; Tzavlaki, Kalliopi; Dadras, Mahsa S; Tan, E-Jean; Hatem, Gad; Maturi, Naga P; Morén, Anita; Wik, Lotta; Watanabe, Yukihide; Savary, Katia; Kamali-Moghaddan, Masood; Uhrbom, Lene; Heldin, Carl-Henrik; Moustakas, Aristidis

    2018-02-16

    Glioblastoma multiforme is a brain malignancy characterized by high heterogeneity, invasiveness, and resistance to current therapies, attributes related to the occurrence of glioma stem cells (GSCs). Transforming growth factor β (TGFβ) promotes self-renewal and bone morphogenetic protein (BMP) induces differentiation of GSCs. BMP7 induces the transcription factor Snail to promote astrocytic differentiation in GSCs and suppress tumor growth in vivo. We demonstrate that Snail represses stemness in GSCs. Snail interacts with SMAD signaling mediators, generates a positive feedback loop of BMP signaling and transcriptionally represses the TGFB1 gene, decreasing TGFβ1 signaling activity. Exogenous TGFβ1 counteracts Snail function in vitro, and in vivo promotes proliferation and re-expression of Nestin, confirming the importance of TGFB1 gene repression by Snail. In conclusion, novel insight highlights mechanisms whereby Snail differentially regulates the activity of the opposing BMP and TGFβ pathways, thus promoting an astrocytic fate switch and repressing stemness in GSCs.

  14. Production of outer membrane vesicles (OMV in batch cultivation of Neisseria meningitidis serogroup B Produção de vesículas da membrana externa (OMV em cultivo batelada de Neisseria meningitidis sorogrupo B

    Directory of Open Access Journals (Sweden)

    Silvia Santos

    2006-12-01

    Full Text Available Meningococcal disease is an important cause of death and morbidity throughout the world. Nearly 330,000 cases and 35,000 deaths occur yearly. Neisseria meningitidis, serogroup B strain N.44/89, is prevalent in Brazil. Its outer membrane vesicles (OMV with iron regulated proteins (IRP are released to the culture medium and are used as antigen for vaccine production. In order to have knowledge about the kinetic parameters, especially the final OMV concentration values, 20-h batch cultivations were carried out in Catlin medium with iron restriction. Process conditions comprised: 7 L bioreactor, 36ºC, 0.5 atm, overlay air flowrate of 1 L/min, agitation varying from 250 rpm to 850 rpm and dissolved oxygen control set at 10% of saturation condition. Biomass was determined by optical density at 540 nm and dry weight. Glycerol, lactate, pH and dissolved oxygen were measured from samples taken during cultivation. Outer membrane vesicle (OMV concentration was determined by Lowry's method after ultracentrifugation. IRP presence was verified by SDS-PAGE. Highest biomass value, corresponding to the highest initial lactate concentration (7.84 g/L was achieved at the 9th hour process time corresponding to 1.0 g/L dry biomass and 2.3 optical density at 540 nm. Lactate consumption was directly related to cell growth (yield factor: 0.24 g dry biomass / g lactate. Glycerol concentration in the medium did not change significantly during the process. OMV concentration reached the highest value of 80 mg/L at end cultivation time. The obtained results suggest that lactate is a main limiting growth factor and the maximum amount of antigen is obtained during stationary growth and cell death phases.A doença meningocócica é uma causa importante de morte a nível mundial. Aproximadamente 330.000 casos e 35.000 mortes ocorrem anualmente. A cepa N.44/89 do sorogrupo B de Neisseria meningitidis é prevalente no Brasil. Suas vesículas de membrana externa (OMV - "outer

  15. 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...

  16. Lipo-oligosaccharide immunotyping of Neisseria meningitidis by a whole-cell ELISA with monoclonal antibodies.

    Science.gov (United States)

    Scholten, R J; Kuipers, B; Valkenburg, H A; Dankert, J; Zollinger, W D; Poolman, J T

    1994-10-01

    To assess the applicability of a whole-cell ELISA (WCE) with monoclonal antibodies (MAbs) for lipo-oligosaccharide (LOS) immunotyping of Neisseria meningitidis, 675 meningococcal isolates obtained in 1989 and 1990 in the Netherlands and 57 isolates collected in 1974, of which the immunotype had been determined previously by microprecipitation, were analysed. Despite the lack of specific MAbs for L2 and L4, an algorithm was developed for the assignment of immunotypes on the basis of the reaction patterns of the reference strains and these isolates to a combination of 14 MAbs. The immunotypes found by WCE were in accordance with those obtained by microprecipitation and the results from WCE were reproducible. The distribution of immunotypes among isolates of the various serogroups in the Netherlands in 1989-1990 is presented. Based on the reaction patterns of the isolates, two main categories of related immunotypes could be distinguished among isolates of serogroups B and C: L2/L4 and L3/L1/L8. Some isolates of the latter category were of one immunotype, but many isolates expressed one or two additional immunotypes, either strongly or weakly, indicating that the differences in this category are quantitative rather than qualitative. The results of this study have demonstrated that the WCE method for LOS immunotyping is easily applicable and provides better definition of test strains for in-vitro bactericidal assays and research into pathogenesis.

  17. The Neisseria meningitidis CRISPR-Cas9 System Enables Specific Genome Editing in Mammalian Cells

    Science.gov (United States)

    Lee, Ciaran M; Cradick, Thomas J; Bao, Gang

    2016-01-01

    The clustered regularly-interspaced short palindromic repeats (CRISPR)—CRISPR-associated (Cas) system from Streptococcus pyogenes (Spy) has been successfully adapted for RNA-guided genome editing in a wide range of organisms. However, numerous reports have indicated that Spy CRISPR-Cas9 systems may have significant off-target cleavage of genomic DNA sequences differing from the intended on-target site. Here, we report the performance of the Neisseria meningitidis (Nme) CRISPR-Cas9 system that requires a longer protospacer-adjacent motif for site-specific cleavage, and present a comparison between the Spy and Nme CRISPR-Cas9 systems targeting the same protospacer sequence. The results with the native crRNA and tracrRNA as well as a chimeric single guide RNA for the Nme CRISPR-Cas9 system were also compared. Our results suggest that, compared with the Spy system, the Nme CRISPR-Cas9 system has similar or lower on-target cleavage activity but a reduced overall off-target effect on a genomic level when sites containing three or fewer mismatches are considered. Thus, the Nme CRISPR-Cas9 system may represent a safer alternative for precision genome engineering applications. PMID:26782639

  18. Penicillin resistance compromises Nod1-dependent proinflammatory activity and virulence fitness of neisseria meningitidis.

    Science.gov (United States)

    Zarantonelli, Maria Leticia; Skoczynska, Anna; Antignac, Aude; El Ghachi, Meriem; Deghmane, Ala-Eddine; Szatanik, Marek; Mulet, Céline; Werts, Catherine; Peduto, Lucie; d'Andon, Martine Fanton; Thouron, Françoise; Nato, Faridabano; Lebourhis, Lionel; Philpott, Dana J; Girardin, Stephen E; Vives, Francina Langa; Sansonetti, Philippe; Eberl, Gérard; Pedron, Thierry; Taha, Muhamed-Kheir; Boneca, Ivo G

    2013-06-12

    Neisseria meningitidis is a life-threatening human bacterial pathogen responsible for pneumonia, sepsis, and meningitis. Meningococcal strains with reduced susceptibility to penicillin G (Pen(I)) carry a mutated penicillin-binding protein (PBP2) resulting in a modified peptidoglycan structure. Despite their antibiotic resistance, Pen(I) strains have failed to expand clonally. We analyzed the biological consequences of PBP2 alteration among clinical meningococcal strains and found that peptidoglycan modifications of the Pen(I) strain resulted in diminished in vitro Nod1-dependent proinflammatory activity. In an influenza virus-meningococcal sequential mouse model mimicking human disease, wild-type meningococci induced a Nod1-dependent inflammatory response, colonizing the lungs and surviving in the blood. In contrast, isogenic Pen(I) strains were attenuated for such response and were out-competed by meningococci sensitive to penicillin G. Our results suggest that antibiotic resistance imposes a cost to the success of the pathogen and may potentially explain the lack of clonal expansion of Pen(I) strains. Copyright © 2013 Elsevier Inc. All rights reserved.

  19. Respuesta inmune mucosal inducida por proteoliposoma y cocleato derivados de N. meningitidis serogrupo B

    Directory of Open Access Journals (Sweden)

    Judith del Campo

    2009-08-01

    Full Text Available Mucosal vaccination offers attractive advantages to conventional systemic vaccination. Most pathogens enter or establish infection at mucosal surfaces. This represents an enormous challenge for vaccine development. Nevertheless, the availability of safe and effective adjuvants that function mucosally is the major limitation. Therefore, we investigated the impact of mucosal immunization with the Neisseria meningitidis B proteoliposome (AFPL1, Adjuvant Finlay Proteoliposome 1 and its-derived cochleate (Co, AFCo1. They contain multiple PAMPs as immunopotentiators and have delivery system ability as well as Th1 polarization activity. Groups of female mice were immunized by nasal, oral, intravaginal, or intramuscular routes with three doses with AFPL1/AFCo1 alone or containing ovalbumin or glycoprotein (g D2 from Herpes Simplex Virus type 2 (HSV-2. High levels of specific IgG antibodies were detected in sera of mice vaccinated with either route. However, specific IgA antibodies were produced in saliva and vaginal wash only following mucosal delivering. The polarization to a Th1 pattern was confirmed by testing the induction of IgG2a/IgG2c antibody, positive delayed-type hypersensitivity reactions, and gIFN production. Additionally, AFCo1gD2 showed practically no vaginal HSV-2 replication and 100% protection against lethal vaginal HSV-2 challenge. In conclusion, the results support the use of AFCo1 as potent Th1 adjuvant for mucosal vaccines, particularly for nasal route.

  20. The Neisseria meningitidis CRISPR-Cas9 System Enables Specific Genome Editing in Mammalian Cells.

    Science.gov (United States)

    Lee, Ciaran M; Cradick, Thomas J; Bao, Gang

    2016-03-01

    The clustered regularly-interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) system from Streptococcus pyogenes (Spy) has been successfully adapted for RNA-guided genome editing in a wide range of organisms. However, numerous reports have indicated that Spy CRISPR-Cas9 systems may have significant off-target cleavage of genomic DNA sequences differing from the intended on-target site. Here, we report the performance of the Neisseria meningitidis (Nme) CRISPR-Cas9 system that requires a longer protospacer-adjacent motif for site-specific cleavage, and present a comparison between the Spy and Nme CRISPR-Cas9 systems targeting the same protospacer sequence. The results with the native crRNA and tracrRNA as well as a chimeric single guide RNA for the Nme CRISPR-Cas9 system were also compared. Our results suggest that, compared with the Spy system, the Nme CRISPR-Cas9 system has similar or lower on-target cleavage activity but a reduced overall off-target effect on a genomic level when sites containing three or fewer mismatches are considered. Thus, the Nme CRISPR-Cas9 system may represent a safer alternative for precision genome engineering applications.

  1. Phase variation of Opa proteins of Neisseria meningitidis and the effects of bacterial transformation.

    Science.gov (United States)

    Sadarangani, Manish; Hoe, Claire J; Makepeace, Katherine; van der Ley, Peter; Pollard, Andrew J

    2016-03-01

    Opa proteins are major proteins involved in meningococcal colonization of the nasopharynx and immune interactions. Opa proteins undergo phase variation (PV) due to the presence of the 5'-CTCTT-3' coding repeat (CR) sequence. The dynamics of PV of meningococcal Opa proteins is unknown. Opa PV, including the effect of transformation on PV, was assessed using a panel of Opa-deficient strains of Neisseria meningitidis. Analysis of Opa expression from UK disease-causing isolates was undertaken. Different opa genes demonstrated variable rates of PV, between 6.4 × 10(-4) and 6.9 × 10(-3) per cell per generation. opa genes with a longer CR tract had a higher rate of PV (r(2) = 0.77, p = 0.1212). Bacterial transformation resulted in a 180-fold increase in PV rate. The majority of opa genes in UK disease isolates (315/463, 68.0%) were in the 'on' phase, suggesting the importance of Opa proteins during invasive disease. These data provide valuable information for the first time regarding meningococcal Opa PV. The presence of Opa PV in meningococcal populations and high expression of Opa among invasive strains likely indicates the importance of this protein in bacterial colonization in the human nasopharynx. These findings have potential implications for development of vaccines derived from meningococcal outer membranes.

  2. Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

    Directory of Open Access Journals (Sweden)

    Laura Morelli

    2014-10-01

    Full Text Available A vaccine to prevent infections from the emerging Neisseria meningitidis X (MenX is becoming an urgent issue. Recently MenX capsular polysaccharide (CPS fragments conjugated to CRM197 as carrier protein have been confirmed at preclinical stage as promising candidates for vaccine development. However, more insights about the minimal epitope required for the immunological activity of MenX CPS are needed. We report herein the chemical conjugation of fully synthetic MenX CPS oligomers (monomer, dimer, and trimer to CRM197. Moreover, improvements in some crucial steps leading to the synthesis of MenX CPS fragments are described. Following immunization with the obtained neoglycoconjugates, the conjugated trimer was demonstrated as the minimal fragment possessing immunogenic activity, even though significantly lower than a pentadecamer obtained from the native polymer and conjugated to the same protein. This finding suggests that oligomers longer than three repeating units are possibly needed to mimic the activity of the native polysaccharide.

  3. Methods for identifying Neisseria meningitidis carriers: a multi-center study in the African meningitis belt.

    Directory of Open Access Journals (Sweden)

    Nicole E Basta

    Full Text Available Detection of meningococcal carriers is key to understanding the epidemiology of Neisseria meningitidis, yet no gold standard has been established. Here, we directly compare two methods for collecting pharyngeal swabs to identify meningococcal carriers.We conducted cross-sectional surveys of schoolchildren at multiple sites in Africa to compare swabbing the posterior pharynx behind the uvula (U to swabbing the posterior pharynx behind the uvula plus one tonsil (T. Swabs were cultured immediately and analyzed using molecular methods.One thousand and six paired swab samples collected from schoolchildren in four countries were analyzed. Prevalence of meningococcal carriage was 6.9% (95% CI: 5.4-8.6% based on the results from both swabs, but the observed prevalence was lower based on one swab type alone. Prevalence based on the T swab or the U swab alone was similar (5.2% (95% CI: 3.8-6.7% versus 4.9% (95% CI: 3.6-6.4% respectively (p=0.6. The concordance between the two methods was 96.3% and the kappa was 0.61 (95% CI: 0.50-0.73, indicating good agreement.These two commonly used methods for collecting pharyngeal swabs provide consistent estimates of the prevalence of carriage, but both methods misclassified carriers to some degree, leading to underestimates of the prevalence.

  4. Differential EMG biofeedback for children with ADHD: a control method for neurofeedback training with a case illustration.

    Science.gov (United States)

    Maurizio, S; Liechti, M D; Brandeis, D; Jäncke, L; Drechsler, R

    2013-06-01

    The objective of the present paper was to develop a differential electromyographic biofeedback (EMG-BF) training for children with attention-deficit/hyperactivity disorder (ADHD) matching multiple neurofeedback training protocols in order to serve as a valid control training. This differential EMG-BF training method feeds back activity from arm muscles involved in fine motor skills such as writing and grip force control. Tonic EMG-BF training (activation and deactivation blocks, involving bimanual motor tasks) matches the training of EEG frequency bands, while phasic EMG-BF training (short activation and deactivation trials) was developed as an equivalent to the training of slow cortical potentials. A case description of a child who learned to improve motor regulation in most task conditions and showed a clinically relevant reduction of behavioral ADHD symptoms illustrates the training course and outcome. Differential EMG-BF training is feasible and provides well-matched control conditions for neurofeedback training in ADHD research. Future studies should investigate its value as a specific intervention for children diagnosed with ADHD and comorbid sensorimotor problems.

  5. The control of mesenchymal stem cell differentiation using dynamically tunable surface microgrooves.

    Science.gov (United States)

    Gong, Tao; Zhao, Kun; Yang, Guang; Li, Jinrong; Chen, Hongmei; Chen, Yuping; Zhou, Shaobing

    2014-10-01

    Many studies have demonstrated the potential to modulate stem cell differentiation by using static material substrate surfaces. However, cells actually grow in a dynamically diverse microenvironment in vivo. The regulated signals to the differentiation provided by these materials should not be passive or static but be active and dynamic. To mimic the endogenous cell culture microenvironment, a novel system is designed to realize the dynamic change of the surface geometries as well as a resultant mechanical force using a thermally activated four-stage shape memory polymer. The parallel microgroove surface patterns are fabricated via thermal embossing lithography on the polymer substrate surface. The dynamic microgroove surfaces accompanying with the mechanical force can effectively and significantly regulate the shape and the cytoskeletal arrangement of rBMSC compared with the static patterned and non-patterned surfaces. Cellular and molecular analyses reveal that the spatiotemporally programmed regulation of cell shape is more viable to coax lineage-specific differentiation of stem cell in contrast to the general reports with the static surfaces. Therefore, this study provides a facile strategy in designing and manufacturing an artificial substrate with a mimic natural cellular environment to precisely direct the cell differentiation. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  6. 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.

  7. C-type lectin receptors in the control of T helper cell differentiation

    NARCIS (Netherlands)

    Geijtenbeek, Teunis B. H.; Gringhuis, Sonja I.

    2016-01-01

    Pathogen recognition by C-type lectin receptors (CLRs) expressed by dendritic cells is important not only for antigen presentation, but also for the induction of appropriate adaptive immune responses via T helper (TH) cell differentiation. CLRs act either by themselves or in cooperation with other

  8. Transposon Dysregulation Modulates dWnt4 Signaling to Control Germline Stem Cell Differentiation in Drosophila.

    Directory of Open Access Journals (Sweden)

    Maitreyi Upadhyay

    2016-03-01

    Full Text Available Germline stem cell (GSC self-renewal and differentiation are required for the sustained production of gametes. GSC differentiation in Drosophila oogenesis requires expression of the histone methyltransferase dSETDB1 by the somatic niche, however its function in this process is unknown. Here, we show that dSETDB1 is required for the expression of a Wnt ligand, Drosophila Wingless type mouse mammary virus integration site number 4 (dWnt4 in the somatic niche. dWnt4 signaling acts on the somatic niche cells to facilitate their encapsulation of the GSC daughter, which serves as a differentiation cue. dSETDB1 is known to repress transposable elements (TEs to maintain genome integrity. Unexpectedly, we found that independent upregulation of TEs also downregulated dWnt4, leading to GSC differentiation defects. This suggests that dWnt4 expression is sensitive to the presence of TEs. Together our results reveal a chromatin-transposon-Wnt signaling axis that regulates stem cell fate.

  9. 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

  10. Improved differentiation between knees with cartilage lesions and controls using 7T relaxation time mapping

    Directory of Open Access Journals (Sweden)

    Cory Wyatt

    2015-10-01

    Conclusion: T1ρ imaging at 7T has been established as a viable imaging method for the differentiation of degenerated cartilage despite previous concerns over specific absorption rate and imaging time. The potential increased sensitivity of T1ρ and T2 imaging at 7T may be useful for future studies in the development of OA.

  11. Differential polarization nonlinear optical microscopy with adaptive optics controlled multiplexed beams.

    Science.gov (United States)

    Samim, Masood; Sandkuijl, Daaf; Tretyakov, Ian; Cisek, Richard; Barzda, Virginijus

    2013-09-09

    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.

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

    Science.gov (United States)

    Samim, Masood; Sandkuijl, Daaf; Tretyakov, Ian; Cisek, Richard; Barzda, Virginijus

    2013-01-01

    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. PMID:24022688

  13. Eficácia do moxalactam no tratamento de meningites purulentas causadas por Haemophilus infuenzae e Neisseria meningitidis Efficacy of moxalactam in the treatment of purulent meningitis caused by Haemophilus influenzae and Neisseria meningitidis

    Directory of Open Access Journals (Sweden)

    Hagamenon R. da Silva

    1984-03-01

    Full Text Available Foi avaliada a eficácia do moxalactam no tratamento de meningites em crianças, causadas por H. influenzae (27 casos e N.meningitidis (6 casos. Dos 33 doentes tratados na dose de 100mg/Kg de peso (dose de ataque e 50mg de 12/12 horas por via venosa, 32 curaram-se. A tolerância ao produto foi muito boa, havendo alterações transitórias de transaminases e fosfatase alcalina; em um caso, houve hematoma posapendectomia, provavelmente relacionado ao uso deste antibiotico. Os níveis séricos e liquóricos do produto foram elevados; as concentrações no liquor excederam de muito a concentração bactericida mínima dos germes infectantes. O moxalactam se mostrou seguro e eficaz como terapia primária da meningite causada por H. influenzae e N.meningitidis em crianças.The clinical efficacy and safety of Moxalactam in purulent bacterial meningitis in children caused by H. influenzae (27 patients and N. meningitidis (6 patients was tested in a randon uncontrolled study. Clinical response was considered excelent, with cure of 32 of 33 patients. High levels of Moxalactam were achieved in the blood and cerebro-spinal fluid, with concentrations largely exceeding the minimum bacterial concentration (MIC for the infecting organisms. Tolerance was considered good, with only transient increases of transaminases and alkaline phosphatase in some patients; also, one patient developed a wound hematoma possibly related to Moxalactam therapy.

  14. 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

  15. 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.

  16. Optogenetic control of cell differentiation in channelrhodopsin-2-expressing OS3, a bipotential glial progenitor cell line.

    Science.gov (United States)

    Ono, Kenji; Suzuki, Hiromi; Yamamoto, Ryusei; Sahashi, Hideki; Takido, Yuhei; Sawada, Makoto

    2017-03-01

    Alterations in the intracellular ion environment have been identified as one of the signals playing a critical role in the control of cellular proliferation and differentiation; however, the mechanisms responsible for signal transduction remain unclear. Recent studies have reported that channelrhodopsin-2 (ChR2) is a rapidly gated blue light (BL)-sensitive cation channel suitable for the non-invasive control of ion influx. We herein examined the expression of differentiation-associated markers by photo-activation and its signal transduction in ChR2-expressing OS3 (OS3ChR2) cells, which are clonal bipotential glial progenitor cells. Increases were observed in intracellular Na + and Ca 2+ concentrations in OS3ChR2 cells with BL exposure. Alterations in the intracellular ion environment, particularly in Ca 2+ , led to increases in the expression of oligodendrocyte markers including galactocerebrosides (GalC) and decreases in that of astrocyte markers such as glial fibrillary acidic protein (GFAP). These alterations also triggered activation of the ERK1/2 signaling pathway, which is involved in cell survival, and PI3K/Akt/mTOR signaling pathway, which is involved in oligodendrocyte differentiation, characterized by GalC expression. Moreover, when photo-activated OS3ChR2 cells were injected into mice with lysophosphatidyl choline (LPC)-induced demyelination, deficits in motor function were reduced. Our results demonstrated that signal transduction by ChR2-expressing glial progenitor cells may be controlled through alterations induced in the intracellular ion environment by photo-activation and results in oligodendrocyte differentiation from glial progenitor cells. Our results also suggest that ChR2-expressing glial progenitor cells have potential as a useful tool for therapeutic approaches to brain and spinal cord disorders associated with oligodendrocyte dysfunctions. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. A novel composite adaptive flap controller design by a high-efficient modified differential evolution identification approach.

    Science.gov (United States)

    Li, Nailu; Mu, Anle; Yang, Xiyun; Magar, Kaman T; Liu, Chao

    2018-03-22

    The optimal tuning of adaptive flap controller can improve adaptive flap control performance on uncertain operating environments, but the optimization process is usually time-consuming and it is difficult to design proper optimal tuning strategy for the flap control system (FCS). To solve this problem, a novel adaptive flap controller is designed based on a high-efficient differential evolution (DE) identification technique and composite adaptive internal model control (CAIMC) strategy. The optimal tuning can be easily obtained by DE identified inverse of the FCS via CAIMC structure. To achieve fast tuning, a high-efficient modified adaptive DE algorithm is proposed with new mutant operator and varying range adaptive mechanism for the FCS identification. A tradeoff between optimized adaptive flap control and low computation cost is successfully achieved by proposed controller. Simulation results show the robustness of proposed method and its superiority to conventional adaptive IMC (AIMC) flap controller and the CAIMC flap controllers using other DE algorithms on various uncertain operating conditions. The high computation efficiency of proposed controller is also verified based on the computation time on those operating cases. Copyright © 2018 ISA. Published by Elsevier Ltd. All rights reserved.

  18. 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.

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

    Science.gov (United States)

    Kurtulus, Sema; Tripathi, Pulak; Hildeman, David A

    2012-01-01

    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

  20. 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

  1. Clinical evaluation of a loop-mediated isothermal amplification (LAMP assay for rapid detection of Neisseria meningitidis in cerebrospinal fluid.

    Directory of Open Access Journals (Sweden)

    DoKyung Lee

    Full Text Available Neisseria meningitidis (Nm is a leading causative agent of bacterial meningitis in humans. Traditionally, meningococcal meningitis has been diagnosed by bacterial culture. However, isolation of bacteria from patients' cerebrospinal fluid (CSF is time consuming and sometimes yields negative results. Recently, polymerase chain reaction (PCR-based diagnostic methods of detecting Nm have been considered the gold standard because of their superior sensitivity and specificity compared with culture. In this study, we developed a loop-mediated isothermal amplification (LAMP method and evaluated its ability to detect Nm in cerebrospinal fluid (CSF.We developed a meningococcal LAMP assay (Nm LAMP that targets the ctrA gene. The primer specificity was validated using 16 strains of N. meningitidis (serogroup A, B, C, D, 29-E, W-135, X, Y, and Z and 19 non-N. meningitidis species. Within 60 min, the Nm LAMP detected down to ten copies per reaction with sensitivity 1000-fold more than that of conventional PCR. The LAMP assays were evaluated using a set of 1574 randomly selected CSF specimens from children with suspected meningitis collected between 1998 and 2002 in Vietnam, China, and Korea. The LAMP method was shown to be more sensitive than PCR methods for CSF samples (31 CSF samples were positive by LAMP vs. 25 by PCR. The detection rate of the LAMP method was substantially higher than that of the PCR method. In a comparative analysis of the PCR and LAMP assays, the clinical sensitivity, specificity, positive predictive value, and negative predictive value of the LAMP assay were 100%, 99.6%, 80.6%, and 100%, respectively.Compared to PCR, LAMP detected Nm with higher analytical and clinical sensitivity. This sensitive and specific LAMP method offers significant advantages for screening patients on a population basis and for diagnosis in clinical settings.

  2. 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....

  3. 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.

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

    Science.gov (United States)

    2010-01-01

    osteoblasts, and that the microfilament -based biomechanical remodeling and [Ca2+]i oscillation are inti- mately connected. MSCs can differentiate down the...transfected to transiently suppress the ERM 8 Journal of Biomedicine and Biotechnology -Actin microfilaments and stress fibers -Focal contacts including...membrane with microfilaments but also are now known to regulate signaling. Of particular interest are their interaction with Rho-A. The role of Rho- A

  5. 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

  6. Transcriptional control of effector and memory CD8+ T cell differentiation

    OpenAIRE

    Kaech, Susan M.; Cui, Weiguo

    2012-01-01

    During an infection, T cells can differentiate into multiple types of effector and memory T cells, which help to mediate pathogen clearance and provide long-term protective immunity. These cells can vary in their phenotype, function and location, and in their long-term fate in terms of their ability to populate the memory T cell pool. Over the past decade, the signalling pathways and transcriptional programmes that regulate the formation of heterogeneous populations of effector and memory CD8...

  7. 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...

  8. Genetic differentiation of invasive Aedes albopictus by RAPD-PCR: implications for effective vector control.

    Science.gov (United States)

    Gupta, Shivani; Preet, Shabad

    2014-06-01

    Aedes albopictus is an invasive mosquito species of great concern to public health as it is responsible for the biological transmission of several pathogens causing dengue, chikungunya, yellow fever, etc. In 2009, this mosquito was detected for the first time in Agra City. This study represents the first genetic analysis of A. albopictus from India. Random amplified polymorphic DNA (RAPD) was used to study the genetic structure of A. albopictus in four populations from different larval habitats. Seven RAPD primers produced 141 loci. The results displayed rich genetic variation among larval populations which is evident from high value of genetic differentiation (G ST), i.e. 0.280, indicating a very great genetic differentiation. Effective migration rates were observed to be 1.28, depicting a limited gene flow. According to analysis of molecular variance (AMOVA), the genetic distance between populations was significant (P < 0.05), showing a very high intrapopulation variation (96%) with only 4% variation among populations. Average genetic distances between populations were also calculated using PopGene software. Nei's average genetic distance between these populations was 0.112 (0.05-0.18). The cluster analysis technique of unweighted pair-group mean analysis (UPGMA) method of arithmetic averages was used to develop the phylogenetic tree which clearly shows two clusters of different larval habitats. The findings highlight high genetic differentiation indicating a slight migration rate confirming the recent introduction of this species in Agra region.

  9. Accuracy of real-time PCR, Gram stain and culture for Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae meningitis diagnosis.

    Science.gov (United States)

    Wu, Henry M; Cordeiro, Soraia M; Harcourt, Brian H; Carvalho, Mariadaglorias; Azevedo, Jailton; Oliveira, Tainara Q; Leite, Mariela C; Salgado, Katia; Reis, Mitermayer G; Plikaytis, Brian D; Clark, Thomas A; Mayer, Leonard W; Ko, Albert I; Martin, Stacey W; Reis, Joice N

    2013-01-22

    Although cerebrospinal fluid (CSF) culture is the diagnostic reference standard for bacterial meningitis, its sensitivity is limited, particularly when antibiotics were previously administered. CSF Gram staining and real-time PCR are theoretically less affected by antibiotics; however, it is difficult to evaluate these tests with an imperfect reference standard. CSF from patients with suspected meningitis from Salvador, Brazil were tested with culture, Gram stain, and real-time PCR using S. pneumoniae, N. meningitidis, and H. influenzae specific primers and probes. An antibiotic detection disk bioassay was used to test for the presence of antibiotic activity in CSF. The diagnostic accuracy of tests were evaluated using multiple methods, including direct evaluation of Gram stain and real-time PCR against CSF culture, evaluation of real-time PCR against a composite reference standard, and latent class analysis modeling to evaluate all three tests simultaneously. Among 451 CSF specimens, 80 (17.7%) had culture isolation of one of the three pathogens (40 S. pneumoniae, 36 N. meningitidis, and 4 H. influenzae), and 113 (25.1%) were real-time PCR positive (51 S. pneumoniae, 57 N. meningitidis, and 5 H. influenzae). Compared to culture, real-time PCR sensitivity and specificity were 95.0% and 90.0%, respectively. In a latent class analysis model, the sensitivity and specificity estimates were: culture, 81.3% and 99.7%; Gram stain, 98.2% and 98.7%; and real-time PCR, 95.7% and 94.3%, respectively. Gram stain and real-time PCR sensitivity did not change significantly when there was antibiotic activity in the CSF. Real-time PCR and Gram stain were highly accurate in diagnosing meningitis caused by S. pneumoniae, N. meningitidis, and H. influenzae, though there were few cases of H. influenzae. Furthermore, real-time PCR and Gram staining were less affected by antibiotic presence and might be useful when antibiotics were previously administered. Gram staining, which is

  10. The role of glyceraldehyde 3-phosphate dehydrogenase (GapA-1 in Neisseria meningitidis adherence to human cells

    Directory of Open Access Journals (Sweden)

    Wooldridge Karl G

    2010-11-01

    Full Text Available Abstract Background Glyceraldehyde 3-phosphate dehydrogenases (GAPDHs are cytoplasmic glycolytic enzymes, which although lacking identifiable secretion signals, have also been found localized to the surface of several bacteria (and some eukaryotic organisms; where in some cases they have been shown to contribute to the colonization and invasion of host tissues. Neisseria meningitidis is an obligate human nasopharyngeal commensal which can cause life-threatening infections including septicaemia and meningitis. N. meningitidis has two genes, gapA-1 and gapA-2, encoding GAPDH enzymes. GapA-1 has previously been shown to be up-regulated on bacterial contact with host epithelial cells and is accessible to antibodies on the surface of capsule-permeabilized meningococcal cells. The aims of this study were: 1 to determine whether GapA-1 was expressed across different strains of N. meningitidis; 2 to determine whether GapA-1 surface accessibility to antibodies was dependant on the presence of capsule; 3 to determine whether GapA-1 can influence the interaction of meningococci and host cells, particularly in the key stages of adhesion and invasion. Results In this study, expression of GapA-1 was shown to be well conserved across diverse isolates of Neisseria species. Flow cytometry confirmed that GapA-1 could be detected on the cell surface, but only in a siaD-knockout (capsule-deficient background, suggesting that GapA-1 is inaccessible to antibody in in vitro-grown encapsulated meningococci. The role of GapA-1 in meningococcal pathogenesis was addressed by mutational analysis and functional complementation. Loss of GapA-1 did not affect the growth of the bacterium in vitro. However, a GapA-1 deficient mutant showed a significant reduction in adhesion to human epithelial and endothelial cells compared to the wild-type and complemented mutant. A similar reduction in adhesion levels was also apparent between a siaD-deficient meningococcal strain and an

  11. Renaturalización de complexos proteicos de membrana externa de Neisseria meningitidis en liposomas: estrutura e potencial vacinal

    OpenAIRE

    Freixeiro Díaz, Paula

    2015-01-01

    Aínda que as vacinas baseadas en vesículas de membrana externa son eficaces fronte ás cepas epidémicas de N. meningitidis do serogrupo B, estas continúan a presentar importantes limitacións e estase a realizar un grande esforzo no desenvolvemento de novas vacinas e na reformulación das xa existentes. A resposta inmune fronte a estas vacinas diríxese principalmente fronte aos complexos de porinas. Este traballo pretende un mellor coñecemento dos complexos de porinas e do papel da RmpM mediante...

  12. Nuclear PTEN functions as an essential regulator of SRF-dependent transcription to control smooth muscle differentiation

    Science.gov (United States)

    Horita, Henrick; Wysoczynski, Christina L.; Walker, Lori A.; Moulton, Karen S.; Li, Marcella; Ostriker, Allison; Tucker, Rebecca; McKinsey, Timothy A.; Churchill, Mair E. A.; Nemenoff, Raphael A.; Weiser-Evans, Mary C. M.

    2016-01-01

    Vascular disease progression is associated with marked changes in vascular smooth muscle cell (SMC) phenotype and function. SMC contractile gene expression and, thus differentiation, is under direct transcriptional control by the transcription factor, serum response factor (SRF); however, the mechanisms dynamically regulating SMC phenotype are not fully defined. Here we report that the lipid and protein phosphatase, PTEN, has a novel role in the nucleus by functioning as an indispensible regulator with SRF to maintain the differentiated SM phenotype. PTEN interacts with the N-terminal domain of SRF and PTEN–SRF interaction promotes SRF binding to essential promoter elements in SM-specific genes. Factors inducing phenotypic switching promote loss of nuclear PTEN through nucleo-cytoplasmic translocation resulting in reduced myogenically active SRF, but enhanced SRF activity on target genes involved in proliferation. Overall decreased expression of PTEN was observed in intimal SMCs of human atherosclerotic lesions underlying the potential clinical importance of these findings. PMID:26940659

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

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    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.

  14. 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.

  15. 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. PMID:26516636

  16. 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.

  17. Neisseria meningitidis Type IV Pili Composed of Sequence Invariable Pilins Are Masked by Multisite Glycosylation.

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    Joseph Gault

    2015-09-01

    Full Text Available The ability of pathogens to cause disease depends on their aptitude to escape the immune system. Type IV pili are extracellular filamentous virulence factors composed of pilin monomers and frequently expressed by bacterial pathogens. As such they are major targets for the host immune system. In the human pathogen Neisseria meningitidis, strains expressing class I pilins contain a genetic recombination system that promotes variation of the pilin sequence and is thought to aid immune escape. However, numerous hypervirulent clinical isolates express class II pilins that lack this property. This raises the question of how they evade immunity targeting type IV pili. As glycosylation is a possible source of antigenic variation it was investigated using top-down mass spectrometry to provide the highest molecular precision on the modified proteins. Unlike class I pilins that carry a single glycan, we found that class II pilins display up to 5 glycosylation sites per monomer on the pilus surface. Swapping of pilin class and genetic background shows that the pilin primary structure determines multisite glycosylation while the genetic background determines the nature of the glycans. Absence of glycosylation in class II pilins affects pilus biogenesis or enhances pilus-dependent aggregation in a strain specific fashion highlighting the extensive functional impact of multisite glycosylation. Finally, molecular modeling shows that glycans cover the surface of class II pilins and strongly decrease antibody access to the polypeptide chain. This strongly supports a model where strains expressing class II pilins evade the immune system by changing their sugar structure rather than pilin primary structure. Overall these results show that sequence invariable class II pilins are cloaked in glycans with extensive functional and immunological consequences.

  18. Outer membrane biogenesis in Escherichia coli, Neisseria meningitidis, and Helicobacter pylori: paradigm deviations in H. pylori.

    Science.gov (United States)

    Liechti, George; Goldberg, Joanna B

    2012-01-01

    The bacterial pathogen Helicobacter pylori is capable of colonizing the gastric mucosa of the human stomach using a variety of factors associated with or secreted from its outer membrane (OM). Lipopolysaccharide (LPS) and numerous OM proteins have been shown to be involved in adhesion and immune stimulation/evasion. Many of these factors are essential for colonization and/or pathogenesis in a variety of animal models. Despite this wide array of potential targets present on the bacterial surface, the ability of H. pylori to vary its OM profile limits the effectiveness of vaccines or therapeutics that target any single one of these components. However, it has become evident that the proteins comprising the complexes that transport the majority of these molecules to the OM are highly conserved and often essential. The field of membrane biogenesis has progressed remarkably in the last few years, and the possibility now exists for targeting the mechanisms by which β-barrel proteins, lipoproteins, and LPS are transported to the OM, resulting in loss of bacterial fitness and significant altering of membrane permeability. In this review, the OM transport machinery for LPS, lipoproteins, and outer membrane proteins (OMPs) are discussed. While the principal investigations of these transport mechanisms have been conducted in Escherichia coli and Neisseria meningitidis, here these systems will be presented in the genetic context of ε proteobacteria. Bioinformatic analysis reveals that minimalist genomes, such as that of Helicobacter pylori, offer insight into the smallest number of components required for these essential pathways to function. Interestingly, in the majority of ε proteobacteria, while the inner and OM associated apparatus of LPS, lipoprotein, and OMP transport pathways appear to all be intact, most of the components associated with the periplasmic compartment are either missing or are almost unrecognizable when compared to their E. coli counterparts. Eventual

  19. In vivo adaptation and persistence of Neisseria meningitidis within the nasopharyngeal mucosa.

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    Kay O Johswich

    Full Text Available Neisseria meningitidis (Nme asymptomatically colonizes the human nasopharynx, yet can initiate rapidly-progressing sepsis and meningitis in rare instances. Understanding the meningococcal lifestyle within the nasopharyngeal mucosa, a phase of infection that is prerequisite for disease, has been hampered by the lack of animal models. Herein, we compare mice expressing the four different human carcinoembryonic antigen-related cell adhesion molecules (CEACAMs that can bind the neisserial Opa protein adhesins, and find that expression of human CEACAM1 is necessary and sufficient to establish intranasal colonization. During infection, in vivo selection for phase variants expressing CEACAM1-specific Opa proteins occurs, allowing mucosal attachment and entry into the subepithelial space. Consistent with an essential role for Opa proteins in this process, Opa-deficient meningococci were unable to colonize the CEACAM1-humanized mice. While simple Opa-mediated attachment triggered an innate response regardless of meningococcal viability within the inoculum, persistence of viable Opa-expressing bacteria within the CEACAM1-humanized mice was required for a protective memory response to be achieved. Parenteral immunization with a capsule-based conjugate vaccine led to the accumulation of protective levels of Nme-specific IgG within the nasal mucus, yet the sterilizing immunity afforded by natural colonization was instead conferred by Nme-specific IgA without detectable IgG. Considered together, this study establishes that the availability of CEACAM1 helps define the exquisite host specificity of this human-restricted pathogen, displays a striking example of in vivo selection for the expression of desirable Opa variants, and provides a novel model in which to consider meningococcal infection and immunity within the nasopharyngeal mucosa.

  20. Genotypic and phenotypic modifications of Neisseria meningitidis after an accidental human passage.

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    Hélène Omer

    2011-02-01

    Full Text Available A scientist in our laboratory was accidentally infected while working with Z5463, a Neisseria meningitidis serogroup A strain. She developed severe symptoms (fever, meningism, purpuric lesions that fortunately evolved with antibiotic treatment to complete recovery. Pulse-field gel electrophoresis confirmed that the isolate obtained from the blood culture (Z5463BC was identical to Z5463, more precisely to a fourth subculture of this strain used the week before the contamination (Z5463PI. In order to get some insights into genomic modifications that can occur in vivo, we sequenced these three isolates. All the strains contained a mutated mutS allele and therefore displayed an hypermutator phenotype, consistent with the high number of mutations (SNP, Single Nucleotide Polymorphism detected in the three strains. By comparing the number of SNP in all three isolates and knowing the number of passages between Z5463 and Z5463PI, we concluded that around 25 bacterial divisions occurred in the human body. As expected, the in vivo passage is responsible for several modifications of phase variable genes. This genomic study has been completed by transcriptomic and phenotypic studies, showing that the blood strain used a different haemoglobin-linked iron receptor (HpuA/B than the parental strains (HmbR. Different pilin variants were found after the in vivo passage, which expressed different properties of adhesion. Furthermore the deletion of one gene involved in LOS biosynthesis (lgtB results in Z5463BC expressing a different LOS than the L9 immunotype of Z2491. The in vivo passage, despite the small numbers of divisions, permits the selection of numerous genomic modifications that may account for the high capacity of the strain to disseminate.

  1. Clinical presentation of invasive disease caused by Neisseria meningitidis serogroup Y in Sweden, 1995 to 2012.

    Science.gov (United States)

    Säll, O; Stenmark, B; Glimåker, M; Jacobsson, S; Mölling, P; Olcén, P; Fredlund, H

    2017-07-01

    Over the period 1995-2012, the incidence of invasive meningococcal disease (IMD) caused by Neisseria meningitidis serogroup Y (NmY) increased significantly in Sweden. This is mainly due to the emergence of a predominant cluster named strain type YI subtype 1, belonging to the ST-23 clonal complex (cc). The aim of this study was to examine the clinical picture of patients with invasive disease caused by NmY and to analyse whether the predominant cluster exhibits certain clinical characteristics that might explain the increased incidence. In this retrospective observational study, the medical records available from patients with IMD caused by Nm serogroup Y in Sweden between 1995 and 2012 were systematically reviewed. Patient characteristics, in-hospital findings and outcome were studied and differences between the dominating cluster and other isolates were analysed. Medical records from 175 of 191 patients were retrieved. The median age was 62 years. The all-cause mortality within 30 days of admission was 9% (15/175) in the whole material; 4% (2/54) in the cohort with strain type YI subtype 1 and 11% (12/121) among patients with other isolates. Thirty-three per cent of the patients were diagnosed with meningitis, 19% with pneumonia, 10% with arthritis and 35% were found to have bacteraemia but no apparent organ manifestation. This survey included cases with an aggressive clinical course as well as cases with a relatively mild clinical presentation. There was a trend towards lower mortality and less-severe disease in the cohort with strain type YI subtype 1 compared with the group with other isolates.

  2. Costs of Neisseria meningitidis Group A Disease and Economic Impact of Vaccination in Burkina Faso.

    Science.gov (United States)

    Colombini, Anaïs; Trotter, Caroline; Madrid, Yvette; Karachaliou, Andromachi; Preziosi, Marie-Pierre

    2015-11-15

    Five years since the successful introduction of MenAfriVac in a mass vaccination campaign targeting 1- to 29-year-olds in Burkina Faso, consideration must be given to the optimal strategies for sustaining population protection. This study aims to estimate the economic impact of a range of vaccination strategies in Burkina Faso. We performed a cost-of-illness study, comparing different vaccination scenarios in terms of costs to both households and health systems over a 26-year time horizon. These scenarios are (1) reactive vaccination campaign (baseline comparator); (2) preventive vaccination campaign; (3) routine immunization at 9 months; and (4) a combination of routine and an initial catchup campaign of children under 5. Costs were estimated from a literature review, which included unpublished programmatic documents and peer-reviewed publications. The future disease burden for each vaccination strategy was predicted using a dynamic transmission model of group A Neisseria meningitidis. From 2010 to 2014, the total costs associated with the preventive campaign targeting 1- to 29-year-olds with MenAfriVac were similar to the estimated costs of the reactive vaccination strategy (approximately 10 million US dollars [USD]). Between 2015 and 2035, routine immunization with or without a catch-up campaign of 1- to 4-year-olds is cost saving compared with the reactive strategy, both with and without discounting costs and cases. Most of the savings are accrued from lower costs of case management and household costs resulting from a lower burden of disease. After the initial investment in the preventive strategy, 1 USD invested in the routine strategy saves an additional 1.3 USD compared to the reactive strategy. Prevention strategies using MenAfriVac will be significantly cost saving in Burkina Faso, both for the health system and for households, compared with the reactive strategy. This will protect households from catastrophic expenditures and increase the development

  3. Neurogenic exacerbation of microglial and astrocyte responses to Neisseria meningitidis and Borrelia burgdorferi.

    Science.gov (United States)

    Chauhan, Vinita S; Sterka, David G; Gray, David L; Bost, Kenneth L; Marriott, Ian

    2008-06-15

    Although glial cells are recognized for their roles in maintaining neuronal function, there is growing appreciation of the ability of resident CNS cells to initiate and/or augment inflammation following trauma or infection. The tachykinin, substance P (SP), is well known to augment inflammatory responses at peripheral sites and its presence throughout the CNS raises the possibility that this neuropeptide might serve a similar function within the brain. In support of this hypothesis, we have recently demonstrated the expression of high affinity receptors for SP (Neurokinin-1 (NK-1) receptors) on microglia and shown that this tachykinin can significantly elevate bacterially induced inflammatory prostanoid production by isolated cultures of these cells. In the present study, we demonstrate that endogenous SP/NK-1R interactions are an essential component in the initiation and/or progression of CNS inflammation in vivo following exposure to two clinically relevant bacterial CNS pathogens, Neisseria meningitidis and Borrelia burgdorferi. We show that in vivo elevations in inflammatory cytokine production and decreases in the production of an immunosuppressive cytokine are markedly attenuated in mice genetically deficient in the expression of the NK-1R or in mice treated with a specific NK-1R antagonist. Furthermore, we have used isolated cultures of microglia and astrocytes to demonstrate that SP can augment inflammatory cytokine production by these resident CNS cell types following exposure to either of these bacterial pathogens. Taken together, these studies indicate a potentially important role for neurogenic exacerbation of resident glial immune responses in CNS inflammatory diseases, such as bacterial meningitis.

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

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    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.

  5. Circulating molecules that control brown/beige adipocyte differentiation and thermogenic capacity.

    Science.gov (United States)

    Ludwig, Raissa G; Rocha, Andréa L; Mori, Marcelo A

    2018-01-31

    Obesity may be counteracted by increased energy expenditure. Circulating molecules act in the adipose tissue to influence brown and beige adipocyte function, differentiation, and thermogenic capacity, which in turn affects substrate utilization and impacts energy balance at the organismal level. These molecules have been envisioned as biomarkers and potential candidates for pharmacological interventions to treat obesity. Here we summarize studies that demonstrate the roles of endogenous circulating molecules of a wide variety in regulating the thermogenic potential of brown and beige fat cells. This review describes the state-of-the-art in the field and helps researchers to prioritize their targets in future studies. © 2018 International Federation for Cell Biology.

  6. Transcriptional control of effector and memory CD8+ T cell differentiation.

    Science.gov (United States)

    Kaech, Susan M; Cui, Weiguo

    2012-11-01

    During an infection, T cells can differentiate into multiple types of effector and memory T cells, which help to mediate pathogen clearance and provide long-term protective immunity. These cells can vary in their phenotype, function and location, and in their long-term fate in terms of their ability to populate the memory T cell pool. Over the past decade, the signalling pathways and transcriptional programmes that regulate the formation of heterogeneous populations of effector and memory CD8(+) T cells have started to be characterized, and this Review discusses the major advances in these areas.

  7. 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.

  8. 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.

  9. Altered Differential Control of Sympathetic Outflow Following Sedentary Conditions: Role of Subregional Neuroplasticity in the RVLM

    Science.gov (United States)

    Subramanian, Madhan; Mueller, Patrick J.

    2016-01-01

    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. PMID:27486405

  10. Microprocessor Activity Controls Differential miRNA Biogenesis In Vivo

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    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.

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

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    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.

  12. An Orchestrated Intron Retention Program in Meiosis Controls Timely Usage of Transcripts during Germ Cell Differentiation.

    Science.gov (United States)

    Naro, Chiara; Jolly, Ariane; Di Persio, Sara; Bielli, Pamela; Setterblad, Niclas; Alberdi, Antonio J; Vicini, Elena; Geremia, Raffaele; De la Grange, Pierre; Sette, Claudio

    2017-04-10

    Global transcriptome reprogramming during spermatogenesis ensures timely expression of factors in each phase of male germ cell differentiation. Spermatocytes and spermatids require particularly extensive reprogramming of gene expression to switch from mitosis to meiosis and to support gamete morphogenesis. Here, we uncovered an extensive alternative splicing program during this transmeiotic differentiation. Notably, intron retention was largely the most enriched pattern, with spermatocytes showing generally higher levels of retention compared with spermatids. Retained introns are characterized by weak splice sites and are enriched in genes with strong relevance for gamete function. Meiotic intron-retaining transcripts (IRTs) were exclusively localized in the nucleus. However, differently from other developmentally regulated IRTs, they are stable RNAs, showing longer half-life than properly spliced transcripts. Strikingly, fate-mapping experiments revealed that IRTs are recruited onto polyribosomes days after synthesis. These studies reveal an unexpected function for regulated intron retention in modulation of the timely expression of select transcripts during spermatogenesis. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  13. Finite difference numerical methods for boundary control problems governed by hyperbolic partial differential equations

    Science.gov (United States)

    Chen, G.; Zheng, Q.; Coleman, M.; Weerakoon, S.

    1983-01-01

    This paper briefly reviews convergent finite difference schemes for hyperbolic initial boundary value problems and their applications to boundary control systems of hyperbolic type which arise in the modelling of vibrations. These difference schemes are combined with the primal and the dual approaches to compute the optimal control in the unconstrained case, as well as the case when the control is subject to inequality constraints. Some of the preliminary numerical results are also presented.

  14. Akt2-mediated phosphorylation of Pitx2 controls Ccnd1 mRNA decay during muscle cell differentiation.

    Science.gov (United States)

    Gherzi, R; Trabucchi, M; Ponassi, M; Gallouzi, I-E; Rosenfeld, M G; Briata, P

    2010-06-01

    Paired-like homeodomain 2 (Pitx2), first identified as the gene responsible for the Axenfeld-Rieger syndrome, encodes a protein factor that, controlling cell proliferation in a tissue-specific manner, has a crucial role in morphogenesis. During embryonic development, Pitx2 exerts a role in the expansion of muscle progenitors and is expressed at all stages of myogenic progression. In this study, we show that Pitx2 is phosphorylated by the protein kinase Akt2 and is necessary to ensure proper C2C12 myoblast proliferation and differentiation. Pitx2 associates with a ribonucleoprotein complex that includes the mRNA stabilizing factor HuR and sustains Ccnd1 (also known as Cyclin D1) expression, thereby prolonging its mRNA half-life. When the differentiation program is initiated, phosphorylation by Akt2 impairs the ability of Pitx2 to associate with the Ccnd1 mRNA-stabilizing complex that includes HuR and, as a consequence, Ccnd1 mRNA half-life is shortened. We propose that unphosphorylated Pitx2 is required to favor HuR-mediated Ccnd1 mRNA stabilization, thus sustaining myoblast proliferation. Upon Akt2-phosphorylation, the complex Pitx2/HuR/Ccnd1 mRNA dissociates and Ccnd1 mRNA is destabilized. These events contribute to the switch of C2C12 cells from a proliferating to a differentiating phenotype.

  15. Aire controls the differentiation program of thymic epithelial cells in the medulla for the establishment of self-tolerance

    Science.gov (United States)

    Yano, Masashi; Kuroda, Noriyuki; Han, Hongwei; Meguro-Horike, Makiko; Nishikawa, Yumiko; Kiyonari, Hiroshi; Maemura, Kentaro; Yanagawa, Yuchio; Obata, Kunihiko; Takahashi, Satoru; Ikawa, Tomokatsu; Satoh, Rumi; Kawamoto, Hiroshi; Mouri, Yasuhiro; Matsumoto, Mitsuru

    2008-01-01

    The roles of autoimmune regulator (Aire) in the expression of the diverse arrays of tissue-restricted antigen (TRA) genes from thymic epithelial cells in the medulla (medullary thymic epithelial cells [mTECs]) and in organization of the thymic microenvironment are enigmatic. We approached this issue by creating a mouse strain in which the coding sequence of green fluorescent protein (GFP) was inserted into the Aire locus in a manner allowing concomitant disruption of functional Aire protein expression. We found that Aire+ (i.e., GFP+) mTECs were the major cell types responsible for the expression of Aire-dependent TRA genes such as insulin 2 and salivary protein 1, whereas Aire-independent TRA genes such as C-reactive protein and glutamate decarboxylase 67 were expressed from both Aire+ and Aire− mTECs. Remarkably, absence of Aire from mTECs caused morphological changes together with altered distribution of mTECs committed to Aire expression. Furthermore, we found that the numbers of mTECs that express involucrin, a marker for terminal epidermal differentiation, were reduced in Aire-deficient mouse thymus, which was associated with nearly an absence of Hassall's corpuscle-like structures in the medulla. Our results suggest that Aire controls the differentiation program of mTECs, thereby organizing the global mTEC integrity that enables TRA expression from terminally differentiated mTECs in the thymic microenvironment. PMID:19015306

  16. 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.

  17. C/ebpα controls osteoclast terminal differentiation, activation, function, and postnatal bone homeostasis through direct regulation of Nfatc1.

    Science.gov (United States)

    Chen, Wei; Zhu, Guochun; Tang, Jun; Zhou, Hou-De; Li, Yi-Ping

    2018-03-01

    Osteoclast lineage commitment and differentiation have been studied extensively, although the mechanism by which transcription factor(s) control osteoclast terminal differentiation, activation, and function remains unclear. CCAAT/enhancer-binding protein α (C/ebpα) has been reported to be a key regulator of osteoclast cell lineage commitment, yet C/ebpα's roles in osteoclast terminal differentiation, activation and function, and bone homeostasis, under physiological or pathological conditions, have not been studied because newborn C/ebpα-null mice die within several hours after birth. Furthermore, the function of C/ebpα in osteoclast terminal differentiation, activation, and function is largely unknown. Herein, we generated and analyzed an osteoclast-specific C/ebpα conditional knockout (CKO) mouse model via Ctsk-Cre mice and found that C/ebpα-deficient mice exhibited a severe osteopetrosis phenotype due to impaired osteoclast terminal differentiation, activation, and function, including mildly reduced osteoclast number, impaired osteoclast polarization, actin formation, and bone resorption, which demonstrated the novel function of C/ebpα in cell function and terminal differentiation. Interestingly, C/ebpα deficiency did not affect bone formation or monocyte/macrophage development. Our results further demonstrated that C/ebpα deficiency suppressed the expression of osteoclast functional genes, e.g. encoding cathepsin K (Ctsk), Atp6i (Tcirg1), and osteoclast regulator genes, e.g. encoding c-fos (Fos), and nuclear factor of activated T-cells 1 (Nfatc1), while having no effect on Pu.1 (Spi1) expression. Promoter activity mapping and ChIP assay defined the critical cis-regulatory element (CCRE) in the promoter region of Nfatc1, and also showed that the CCREs were directly associated with C/ebpα, which enhanced the promoter's activity. The deficiency of C/ebpα in osteoclasts completely blocked ovariectomy-induced bone loss, indicating that C/ebpα is a

  18. Identificación In Silico del mimetismo molecular entre Epitopes T de Neisseria meningitidis B y el proteoma humano

    Directory of Open Access Journals (Sweden)

    Alexander Batista-Duharte

    2013-09-01

    Full Text Available El objetivo del estudio fue determinar los epítopes T de cuatro de las proteínas antigénicas más frecuentes de la membrana externa de Neisseria meningitidis B e identificar los sitios más relevantes donde existe mimetismo molecular para estos epítopes en seres humanos. Para ello se realizó un estudio in silico (estudios que usan herramientas bioinformáticas usando las bases de datos SWISS-PROT/TrEMBL SYFPEITHI y FASTA, las cuales se emplearon para la determinación de las secuencias proteicas, la predicción de los epítopes T CD4 y CD8, y la determinación del mimetismo molecular en humanos, respectivamente. Se encontró similitud molecular en varias proteínas humanas presentes en diferentes órganos y tejidos, entre ellos: hígado, piel y epitelios, cerebro, sistema linfático y testículos, destacando las encontradas en estos últimos, ya que ellas mostraron la frecuencia más alta de secuencias miméticas. Este hallazgo ayuda a comprender el éxito de N. meningitidis B para colonizar tejidos humanos, el fracaso de ciertas vacunas contra esta bacteria e incluso ayuda a explicar posibles reacciones autoimmunes asociadas a la infección o vacunación.

  19. Assessment of a two-step nucleic acid amplification assay for detection of Neisseria meningitidis followed by capsular genogrouping

    Directory of Open Access Journals (Sweden)

    Maria C Rebelo

    2006-11-01

    Full Text Available Immediate prevention of meningococcal disease relies in part on the prompt treatment with antibiotics of household and other close contacts of cases; however intervention with effective vaccination relies on identification of serogroup-causing strains. Parenteral antibiotic for patient with suspected meningococcal disease before hospital admission is currently recommended. Laboratory standard methods are hindered by failure to detect bacteria by this medical approach to improve patient prognosis. We assessed two polymerase chain reaction (PCR assays to detect (crgA and define the serogroups (siaD, orf-2, and ctrA of Neisseria meningitidis in 120 cerebrospinal fluid (CSF samples from positive cases (culture or antigen detection or direct smear. The PCR sensitivity for the identification of N. meningitidis was 100% (95% confidence interval, CI, 96-100% compared to a sensitivity of 46% for culture (95% CI 37-55%, 61% for latex agglutination test (95% CI 52-70%, and 68% for Gram stain (95% CI 59-76%; PCR specificity was 97% (95% CI 82-100%. PCR correctly identified the serogroups A, B, C, W135, Y, and X in CSF samples with a sensitivity of 88% (95% CI 80-93%; the primer sets were 100% specific. The introduction of PCR-based assays shall increase laboratory confirmed cases, consequently enhancing surveillance of meningococcal disease.

  20. Study of 138 Neisseria meningitidis strains isolated from blood or cerebrospinal fluid in Lombardy between 2007 and 2010

    Directory of Open Access Journals (Sweden)

    Laura Daprai

    2012-06-01

    Full Text Available Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae type b cause the majority of cases of bacterial septicaemia in children and young adults. Disease epidemiology is evolving rapidly due to the introduction of vaccines and changing in bacterial antibiotic-resistance patterns. (Asymptomatic nasopharyngeal colonization with Neisseria meningitides occurs in 5-10% of adult. The aim of this study was to calculate the frequency of each serogroup of this pathogens involved in invasive infection and to study susceptibility to antibiotics of these strains. Between March 2007 and June 2010 we received, from 43 hospitals of Lombardy, 138 strains of Neisseria meningitidis, from 138 patients aged (2-80yrs. The most frequent serogroup was B (58%, followed by serogroup C (34%, serogroup G (4% and W 135 (2%. Serogroup A end X accounted for 1% of invasive infection, each. We observed a decrease in susceptibility towards penicillin in 38% of strains. In addition we studied, by REP- PCR, genotype of 9 strains selected on the basis of epidemiological data.Among these strains, 3 different clusters according to the 3 small epidemic outbreaks occurred between June and September 2009, were recognised. Seven of these strains, although belonged to the same serogroup, brought about two different clusters. The present findings demonstrated that phenotypic data are not sufficient to define epidemic clusters, therefore molecular genotyping is required.

  1. Structure of the P{sub II} signal transduction protein of Neisseria meningitidis at 1.85 Å resolution

    Energy Technology Data Exchange (ETDEWEB)

    Nichols, Charles E. [Division of Structural Biology, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Sainsbury, Sarah; Berrow, Nick S.; Alderton, David [The Oxford Protein Production Facility, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Saunders, Nigel J. [The Bacterial Pathogenesis and Functional Genomics Group, The Sir William Dunn School of Pathology, University of Oxford, South Parks Road, Oxford OX1 3RE (United Kingdom); Stammers, David K. [Division of Structural Biology, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); The Oxford Protein Production Facility, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Owens, Raymond J., E-mail: ray@strubi.ox.ac.uk [The Oxford Protein Production Facility, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom); Division of Structural Biology, Henry Wellcome Building for Genomic Medicine, University of Oxford, Roosevelt Drive, Oxford OX3 7BN (United Kingdom)

    2006-06-01

    The structure of the P{sub II} signal transduction protein of N. meningitidis at 1.85 Å resolution is described. The P{sub II} signal transduction proteins GlnB and GlnK are implicated in the regulation of nitrogen assimilation in Escherichia coli and other enteric bacteria. P{sub II}-like proteins are widely distributed in bacteria, archaea and plants. In contrast to other bacteria, Neisseria are limited to a single P{sub II} protein (NMB 1995), which shows a high level of sequence identity to GlnB and GlnK from Escherichia coli (73 and 62%, respectively). The structure of the P{sub II} protein from N. meningitidis (serotype B) has been solved by molecular replacement to a resolution of 1.85 Å. Comparison of the structure with those of other P{sub II} proteins shows that the overall fold is tightly conserved across the whole population of related proteins, in particular the positions of the residues implicated in ATP binding. It is proposed that the Neisseria P{sub II} protein shares functions with GlnB/GlnK of enteric bacteria.

  2. Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine for infants and toddlers.

    Science.gov (United States)

    Bryant, Kristina A; Marshall, Gary S

    2011-07-01

    The highest rates of invasive meningococcal disease occur in children under 2 years of age, yet as of early 2011 no vaccine was licensed for the youngest infants. However, a novel vaccine consisting of capsular polysaccharides from Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroups C and Y conjugated to tetanus toxoid (HibMenCY-TT; MenHibrix, GlaxoSmithKline) is in the late stages of development. In clinical trials involving more than 7800 children, HibMenCY-TT was shown to be safe and immunogenic when administered at 2, 4, 6 and 12-15 months of age. Anti-polyribosylribitol phosphate antibody responses were noninferior to those elicited by licensed monovalent Hib vaccines, and most vaccinees developed bactericidal antibodies against N. meningitidis serogroups C and Y. The majority of subjects retained antibody responses as far as 3 years after vaccination. If licensed, HibMenCY-TT not only represents an incremental option for protection against invasive Hib, but also has the potential to prevent invasive meningococcal disease without increasing the number of injections.

  3. 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…

  4. 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…

  5. Meningococcal disease in The Netherlands, 1958-1990: a steady increase in the incidence since 1982 partially caused by new serotypes and subtypes of Neisseria meningitidis

    NARCIS (Netherlands)

    Scholten, R. J.; Bijlmer, H. A.; Poolman, J. T.; Kuipers, B.; Caugant, D. A.; van Alphen, L.; Dankert, J.; Valkenburg, H. A.

    1993-01-01

    In order to explain a threefold increase in the incidence of meningococcal disease in the Netherlands during the 1980s, we serotyped and subtyped Neisseria meningitidis isolates recovered between 1958 and 1990 from > 3,000 patients with systemic disease. No single strain could be held responsible

  6. IgA1 antibodies specific for outer membrane protein PorA modulate the interaction between Neisseria meningitidis and the epithelium

    NARCIS (Netherlands)

    Horton, R. E.; Vidarsson, G.; Virji, M.; Williams, N. A.; Heyderman, R. S.

    2009-01-01

    Despite high carriage rates of Neisseria meningitidis, incidence of meningococcal disease remains low, partially due to development of natural immunity. We have previously demonstrated an inverse relationship between salivary anti-meningococcal IgA and disease incidence, but little is known about

  7. Necrotising fasciitis as atypical presentation of infection with emerging Neisseria meningitidis serogroup W (MenW) clonal complex 11, the Netherlands, March 2017

    NARCIS (Netherlands)

    Russcher, Anne; Fanoy, Ewout; van Olden, Ger D. J.; Graafland, Antonie D.; van der Ende, Arie; Knol, Mirjam J.

    2017-01-01

    In March 2017, a patient with necrotising fasciitis caused by Neisseria meningitidis serogroup W (MenW) clonal complex 11 was diagnosed in the Netherlands. Unusual and severe presentations of MenW infections are common in the current European epidemic. In the Netherlands, the incidence of MenW

  8. Interlaboratory comparison of agar dilution and Etest methods for determining the MICs of antibiotics used in management of Neisseria meningitidis infections

    NARCIS (Netherlands)

    Vázquez, Julio A.; Arreaza, Luisa; Block, Colin; Ehrhard, Ingrid; Gray, Stephen J.; Heuberger, Sigrid; Hoffmann, Steen; Kriz, Paula; Nicolas, Pierre; Olcen, Per; Skoczynska, Anna; Spanjaard, Lodewijk; Stefanelli, Paola; Taha, Muhamed-Kheir; Tzanakaki, Georgina

    2003-01-01

    Previous studies have shown that there is considerable variation in the methods and media used to determine the susceptibility of Neisseria meningitidis to antimicrobial agents in different countries. In this study, national and regional reference laboratories used a standardized methodology to

  9. 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

    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...... with a continuous glucose monitor (CGM) frequently observing the glucose level. Automatic control of the insulin pump based on CGM observations would ease the burden of constant diabetes treatment and management. We have developed a controller designed to keep the blood glucose level in the normal range...... by adjusting the size of insulin infusions from the pump based on model predictive control (MPC). A clinical pilot study to test the performance of the MPC controller overnight was performed. The conclusion was that the controller relied too much on the local trend of the blood glucose level which is a problem...

  10. 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.

  11. Differential control of muscle mass in type 1 and type 2 diabetes mellitus.

    Science.gov (United States)

    Sala, David; Zorzano, Antonio

    2015-10-01

    Diabetes mellitus--whether driven by insulin deficiency or insulin resistance--causes major alterations in muscle metabolism. These alterations have an impact on nutrient handling, including the metabolism of glucose, lipids, and amino acids, and also on muscle mass and strength. However, the ways in which the distinct forms of diabetes affect muscle mass differ greatly. The most common forms of diabetes mellitus are type 1 and type 2. Thus, whereas type 1 diabetic subjects without insulin treatment display a dramatic loss of muscle, most type 2 diabetic subjects show no changes or even an increase in muscle mass. However, the most commonly used rodent models of type 2 diabetes are characterized by muscle atrophy and do not mimic the features of the disease in humans in terms of muscle mass. In this review, we analyze the processes that are differentially regulated under these forms of diabetes and propose regulatory mechanisms to explain them.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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.

  17. 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.

  18. 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 ...

  19. Adaptive Neural Control Based on High Order Integral Chained Differentiator for Morphing Aircraft

    OpenAIRE

    Wu, Zhonghua; Lu, Jingchao; Rajput, Jahanzeb; Shi, Jingping; Ma, Wen

    2015-01-01

    This paper presents an adaptive neural control for the longitudinal dynamics of a morphing aircraft. Based on the functional decomposition, it is reasonable to decompose the longitudinal dynamics into velocity and altitude subsystems. As for the velocity subsystem, the adaptive control is proposed via dynamic inversion method using neural network. To deal with input constraints, the additional compensation system is employed to help engine recover from input saturation rapidly. The highlight ...

  20. Adaptive fuzzy control of underactuated robotic systems with the use of differential flatness theory

    Science.gov (United States)

    Rigatos, Gerasimos G.

    2013-10-01

    An adaptive fuzzy controller is designed for a class of underactuated nonlinear robotic manipulators, under the constraint that the system's model is unknown. The control algorithm aims at satisfying the H∞ tracking performance criterion, which means that the influence of the modeling errors and the external disturbances on the tracking error is attenuated to an arbitrary desirable level. After transforming the robotic system into the canonical form, the resulting control inputs are shown to contain nonlinear elements which depend on the system's parameters. The nonlinear terms which appear in the control inputs are approximated with the use of neuro-fuzzy networks. It is shown that a suitable learning law can be defined for the aforementioned neuro-fuzzy approximators so as to preserve the closed-loop system stability. With the use of Lyapunov stability analysis it is proven that the proposed adaptive fuzzy control scheme results in H∞ tracking performance. The efficiency of the proposed adaptive fuzzy control scheme is checked in the case of a 2-DOF planar robotic manipulator that has the structure of a closed-chain mechanism.

  1. Radioprotective effect of vitamin E on salivary glands after radioiodine therapy for differentiated thyroid cancer: a randomized-controlled trial.

    Science.gov (United States)

    Upadhyaya, Arun; Zhou, Pingping; Meng, Zhaowei; Wang, Peng; Zhang, Guizhi; Jia, Qiang; Tan, Jian; Li, Xue; Hu, Tianpeng; Liu, Na; Wang, Sen; Liu, Xiaoxia; Wang, Huiying; Zhang, Chunmei; Zhao, Fengxiao; Yan, Ziyu; Wang, Xiaoran; Zhang, Xuemeng; Zhang, Wan

    2017-11-01

    This study aimed to examine the radioprotective effect of vitamin E on salivary glands after radioactive iodine (I) therapy in patients with differentiated thyroid cancer. Eighty-two patients with differentiated thyroid cancer were enrolled in this study. They were divided randomly into four groups (control group: 22 cases, group A: 23 cases, group B: 22 cases, and group C: 15 cases) before postsurgical ablation therapy with 100 mCi I. The patients in groups A, B, and C received vitamin E 100, 200, and 300 mg/day orally, respectively, for a duration of 1 week before to 4 weeks after I therapy. Salivary gland function was assessed using salivary gland scintigraphy immediately before and 6 months after I therapy. Uptake fraction (UF), uptake index (UI), excretion fraction (EF), and excretion ratio (ER) of each salivary gland were measured and compared. On comparison between before and after I therapy in the control group, there was a significant decrease in UF of both right and left parotid glands (all Pgland (Pgland (Pgland and both submandibular glands (all Pgland (Pgland (Pglands (all Psalivary scintigraphy parameters among the four groups, there was a significant difference in ΔUI of the right parotid gland (Pglands (all Pgland (Pgland (Pglands after I therapy.

  2. 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.

  3. 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

  4. 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....

  5. 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

  6. 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

  7. 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.

  8. 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.

  9. 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.

  10. Structure and assembly of a trans-periplasmic channel for type IV pili in Neisseria meningitidis.

    Directory of Open Access Journals (Sweden)

    Jamie-Lee Berry

    2012-09-01

    Full Text Available Type IV pili are polymeric fibers which protrude from the cell surface and play a critical role in adhesion and invasion by pathogenic bacteria. The secretion of pili across the periplasm and outer membrane is mediated by a specialized secretin protein, PilQ, but the way in which this large channel is formed is unknown. Using NMR, we derived the structures of the periplasmic domains from N. meningitidis PilQ: the N-terminus is shown to consist of two β-domains, which are unique to the type IV pilus-dependent secretins. The structure of the second β-domain revealed an eight-stranded β-sandwich structure which is a novel variant of the HSP20-like fold. The central part of PilQ consists of two α/β fold domains: the structure of the first of these is similar to domains from other secretins, but with an additional α-helix which links it to the second α/β domain. We also determined the structure of the entire PilQ dodecamer by cryoelectron microscopy: it forms a cage-like structure, enclosing a cavity which is approximately 55 Å in internal diameter at its largest extent. Specific regions were identified in the density map which corresponded to the individual PilQ domains: this allowed us to dock them into the cryoelectron microscopy density map, and hence reconstruct the entire PilQ assembly which spans the periplasm. We also show that the C-terminal domain from the lipoprotein PilP, which is essential for pilus assembly, binds specifically to the first α/β domain in PilQ and use NMR chemical shift mapping to generate a model for the PilP:PilQ complex. We conclude that passage of the pilus fiber requires disassembly of both the membrane-spanning and the β-domain regions in PilQ, and that PilP plays an important role in stabilising the PilQ assembly during secretion, through its anchorage in the inner membrane.

  11. Identifying optimal vaccination strategies for serogroup A Neisseria meningitidis conjugate vaccine in the African meningitis belt.

    Directory of Open Access Journals (Sweden)

    Sara Tartof

    Full Text Available The optimal long-term vaccination strategies to provide population-level protection against serogroup A Neisseria meningitidis (MenA are unknown. We developed an age-structured mathematical model of MenA transmission, colonization, and disease in the African meningitis belt, and used this model to explore the impact of various vaccination strategies.The model stratifies the simulated population into groups based on age, infection status, and MenA antibody levels. We defined the model parameters (such as birth and death rates, age-specific incidence rates, and age-specific duration of protection using published data and maximum likelihood estimation. We assessed the validity of the model by comparing simulated incidence of invasive MenA and prevalence of MenA carriage to observed incidence and carriage data.The model fit well to observed age- and season-specific prevalence of carriage (mean pseudo-R2 0.84 and incidence of invasive disease (mean R2 0.89. The model is able to reproduce the observed dynamics of MenA epidemics in the African meningitis belt, including seasonal increases in incidence, with large epidemics occurring every eight to twelve years. Following a mass vaccination campaign of all persons 1-29 years of age, the most effective modeled vaccination strategy is to conduct mass vaccination campaigns every 5 years for children 1-5 years of age. Less frequent campaigns covering broader age groups would also be effective, although somewhat less so. Introducing conjugate MenA vaccine into the EPI vaccination schedule at 9 months of age results in higher predicted incidence than periodic mass campaigns.We have developed the first mathematical model of MenA in Africa to incorporate age structures and progressively waning protection over time. Our model accurately reproduces key features of MenA epidemiology in the African meningitis belt. This model can help policy makers consider vaccine program effectiveness when determining the

  12. Differences in the population structure of Neisseria meningitidis in two Australian states: Victoria and Western Australia.

    Directory of Open Access Journals (Sweden)

    Shakeel Mowlaboccus

    Full Text Available Neisseria meningitidis is the causative agent of invasive meningococcal disease (IMD. A recombinant vaccine called Bexsero® incorporates four subcapsular antigens (fHbp, NHBA, NadA and PorA which are used to assign a Bexsero® antigen sequence type (BAST to each meningococcal strain. The vaccine elicits an immune response against combinations of variants of these antigens which have been grouped into specific BAST profiles that have been shown to have different distributions within geographical locations thus potentially affecting the efficacy of the vaccine. In this study, invasive meningococcal disease isolates from the western seaboard of Australia (Western Australia; WA were compared to those from the south-eastern seaboard (Victoria; VIC from 2008 to 2012. Whole-genome sequencing (WGS of 131 meningococci from VIC and 70 meningococci from WA were analysed for MLST, FetA and BAST profiling. Serogroup B predominated in both jurisdictions and a total of 10 MLST clonal complexes (cc were shared by both states. Isolates belonging to cc22, cc103 and cc1157 were unique to VIC whilst isolates from cc60 and cc212 were unique to WA. Clonal complex 41/44 represented one-third of the meningococcal population in each state but the predominant ST was locally different: ST-6058 in VIC and ST-146 in WA. Of the 108 BAST profiles identified in this collection, only 9 BASTs were simultaneously observed in both states. A significantly larger proportion of isolates in VIC harboured alleles for the NHBA-2 peptide and fHbp-1, antigenic variants predicted to be covered by the Bexsero® vaccine. The estimate for vaccine coverage in WA (47.1% [95% CI: 41.1-53.1%] was significantly lower than that in VIC (66.4% [95% CI: 62.3-70.5%]. In conclusion, the antigenic structure of meningococci causing invasive disease in two geographically distinct states of Australia differed significantly during the study period which may affect vaccine effectiveness and highlights the

  13. Real-time visual feedback of COM and COP motion properties differentially modifies postural control structures.

    Science.gov (United States)

    Kilby, Melissa C; Molenaar, Peter C M; Slobounov, Semyon M; Newell, Karl M

    2017-01-01

    The experiment was setup to investigate the control of human quiet standing through the manipulation of augmented visual information feedback of selective properties of the motion of two primary variables in postural control: center of pressure (COP) and center of mass (COM). Five properties of feedback information were contrasted to a no feedback dual-task (watching a movie) control condition to determine the impact of visual real-time feedback on the coordination of the joint motions in postural control in both static and dynamic one-leg standing postures. The feedback information included 2D COP or COM position and macro variables derived from the COP and COM motions, namely virtual time-to-contact (VTC) and the COP-COM coupling. The findings in the static condition showed that the VTC and COP-COM coupling feedback conditions decreased postural motion more than the 2D COP or COM positional information. These variables also induced larger sway amplitudes in the dynamic condition showing a more progressive search strategy in exploring the stability limits. Canonical correlation analysis (CCA) found that COP-COM coupling contributed less than the other feedback variables to the redundancy of the system reflected in the common variance between joint motions and properties of sway motion. The COP-COM coupling had the lowest weighting of the motion properties to redundancy under the feedback conditions but overall the qualitative pattern of the joint motion structures was preserved within the respective static and dynamic balance conditions.

  14. 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…

  15. 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 ...

  16. 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.

  17. Prognostic indicators in well-differentiated thyroid carcinoma when controlling for stage and treatment.

    Science.gov (United States)

    Krook, Kaelyn A; Fedewa, Stacey A; Chen, Amy Y

    2015-04-01

    The incidence of thyroid carcinoma is rising. Few studies have examined patient characteristics that influence survival when adjusting for treatment and tumor stage/extent. Retrospective analysis was performed using the Surveillance Epidemiology and End Results registry data among patients diagnosed with well-differentiated thyroid (WDT) carcinoma during 1988-2009. Kaplan-Meir survival curves were used to estimate 5- and 10-year cause-specific and overall survival differences by sociodemographics, clinical characteristics, and treatment. Multivariate Cox proportional hazard models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). A total of 83,985 patients were identified with WDT carcinoma. Blacks had higher hazard of death at 5 years (HR, 1.67; 95% CI, 1.42-1.96) and 10 years (HR, 1.57; 95% CI, 1.37-1.80) when compared to Caucasians, but there were no significant differences in cause-specific deaths. Hispanics had higher overall and cause-specific 5-year and 10-year hazard of death (5-year cause-specific: HR, 1.56; 95% CI, 1.23-1.99). Age was the most significant predictor of cause-specific and overall survival, with risk increasing in a nonlinear fashion. After age 45 years, the HR for 5- and 10-year cause-specific survival rose drastically, reaching an HR of 153 for individuals aged 85 years and older (HR, 153.45; 95% CI, 97.84-240.67). Age was the strongest factor associated with WDT cancer in our study. African Americans had worse overall survival, although only Hispanics had a significantly worse cause-specific survival. These factors should be taken into account in counseling patients and treatment planning. © 2014 The American Laryngological, Rhinological and Otological Society, Inc.

  18. Lrp5/β-Catenin Signaling Controls Lung Macrophage Differentiation and Inhibits Resolution of Fibrosis.

    Science.gov (United States)

    Sennello, Joseph A; Misharin, Alexander V; Flozak, Annette S; Berdnikovs, Sergejs; Cheresh, Paul; Varga, John; Kamp, David W; Budinger, G R Scott; Gottardi, Cara J; Lam, Anna P

    2017-02-01

    Previous studies established that attenuating Wnt/β-catenin signaling limits lung fibrosis in the bleomycin mouse model of this disease, but the contribution of this pathway to distinct lung cell phenotypes relevant to tissue repair and fibrosis remains incompletely understood. Using microarray analysis, we found that bleomycin-injured lungs from mice that lack the Wnt coreceptor low density lipoprotein receptor-related protein 5 (Lrp5) and exhibit reduced fibrosis showed enrichment for pathways related to extracellular matrix processing, immunity, and lymphocyte proliferation, suggesting the contribution of an immune-matrix remodeling axis relevant to fibrosis. Activation of β-catenin signaling was seen in lung macrophages using the β-catenin reporter mouse, Axin2 +/LacZ . Analysis of lung immune cells by flow cytometry after bleomycin administration revealed that Lrp5 -/- lungs contained significantly fewer Siglec F low alveolar macrophages, a cell type previously implicated as positive effectors of fibrosis. Macrophage-specific deletion of β-catenin in CD11c cre ;β-catenin flox mice did not prevent development of bleomycin-induced fibrosis but facilitated its resolution by 8 weeks. In a nonresolving model of fibrosis, intratracheal administration of asbestos in Lrp5 -/- mice also did not prevent the development of fibrosis but hindered the progression of fibrosis in asbestos-treated Lrp5 -/- lungs, phenocopying the findings in bleomycin-treated CD11c cre ;β-catenin flox mice. Activation of β-catenin signaling using lithium chloride resulted in worsened fibrosis in wild-type mice, further supporting that the effects of loss of Lrp5 are directly mediated by Wnt/β-catenin signaling. Together, these data suggest that lung myeloid cells are responsive to Lrp5/β-catenin signaling, leading to differentiation of an alveolar macrophage subtype that antagonizes the resolution of lung fibrosis.

  19. Development and characterization of murine monoclonal antibody specific for the P1.4 PorA proteins from strain B:4:P1.(7b.4. of Neisseria meningitidis

    Directory of Open Access Journals (Sweden)

    María Elena Pérez

    2011-08-01

    Full Text Available Neisseria meningitidis isolates are conventionally classified by serosubtyping that characterizes the reactivities of the PorA outer membrane protein variable-region epitopes with monoclonal antibodies. Porins are outer membrane proteins (OMPs of N. meningitidis serogroup B and have attracted study principally for two reasons: their use in the classification of meningococcal isolates into serotype and subtype and as potential components of vaccines against this important pathogen. New murine hybridomas, secreting specific monoclonal antibodies against PorA serotype P1.4 of N. meningitidis serogroup B, were generated using conventional hybridoma procedures. The monoclonal antibodies obtained were characterized by Western blot and whole cell ELISA, using reference strains from different N. meningitidis serotypes and subtypes. All monoclonal antibodies belong to isotype IgG1. Others hybridomas producing MAbs against PorB and FrpB were also obtained.

  20. Electric toothbrush application is a reliable and valid test for differentiating temporomandibular disorders pain patients from controls.

    Science.gov (United States)

    Nixdorf, Donald R; Hemmaty, Azar; Look, John O; Schiffman, Eric L; John, Mike T

    2009-07-30

    Current methods for identifying patients with pain hypersensitivity are sufficiently complex to limit their widespread application in clinical settings. We assessed the reliability and validity of a simple multi-modal vibrotactile stimulus, applied using an electric toothbrush, to evaluate its potential as a screening tool for central sensitization. Fourteen female temporomandibular disorders (TMD) subjects with myofascial pain (RDC/TMD Ia or Ib) and arthralgia (RDC/TMD IIIa) were compared to 13 pain-free controls of matched age and gender. Vibrotactile stimulus was performed with an electric toothbrush, applied with 1 pound pressure for 30 seconds in four locations: over the lateral pole of the temporomandibular joint, masseter, temporalis, and mid-ventral surface of forearm. Pain intensity (0-10) was recorded following the stimulus at 0, 15, 30, and 60 seconds. Test-retest reliability was assessed with measurements from 8 participants, taken 2-12 hours apart. Case versus control differentiation involved comparison of area under the curve (AUC). A receiver operating characteristic (ROC) curve was used to determine cutoff AUC scores for maximum sensitivity and specificity for this multi-modal vibrotactile stimulus. Test-retest reliability resulted in an ICC of 0.87 for all 4 pooled sites. ROC-determined AUC cutoff scores resulted in a sensitivity of 57% and specificity of 92% for all 4 pooled sites. The electric toothbrush stimulus had excellent test-retest reliability. Validity of the scores was demonstrated with modest sensitivity and good specificity for differentiating TMD pain patients from controls, which are acceptable properties for a screening test.

  1. Electric toothbrush application is a reliable and valid test for differentiating temporomandibular disorders pain patients from controls

    Directory of Open Access Journals (Sweden)

    Schiffman Eric L

    2009-07-01

    Full Text Available Abstract Background Current methods for identifying patients with pain hypersensitivity are sufficiently complex to limit their widespread application in clinical settings. We assessed the reliability and validity of a simple multi-modal vibrotactile stimulus, applied using an electric toothbrush, to evaluate its potential as a screening tool for central sensitization. Methods Fourteen female temporomandibular disorders (TMD subjects with myofascial pain (RDC/TMD Ia or Ib and arthralgia (RDC/TMD IIIa were compared to 13 pain-free controls of matched age and gender. Vibrotactile stimulus was performed with an electric toothbrush, applied with 1 pound pressure for 30 seconds in four locations: over the lateral pole of the temporomandibular joint, masseter, temporalis, and mid-ventral surface of forearm. Pain intensity (0–10 was recorded following the stimulus at 0, 15, 30, and 60 seconds. Test-retest reliability was assessed with measurements from 8 participants, taken 2–12 hours apart. Case versus control differentiation involved comparison of area under the curve (AUC. A receiver operating characteristic (ROC curve was used to determine cutoff AUC scores for maximum sensitivity and specificity for this multi-modal vibrotactile stimulus. Results Test-retest reliability resulted in an ICC of 0.87 for all 4 pooled sites. ROC-determined AUC cutoff scores resulted in a sensitivity of 57% and specificity of 92% for all 4 pooled sites. Conclusion The electric toothbrush stimulus had excellent test-retest reliability. Validity of the scores was demonstrated with modest sensitivity and good specificity for differentiating TMD pain patients from controls, which are acceptable properties for a screening test.

  2. 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

    2016-01-01

    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. PMID:26666261

  3. Anticipatory Electrodermal Response as a Differentiating Somatic Marker Between Children with ADHD and Controls.

    Science.gov (United States)

    Odle, Michie; Ouellette, Judith A

    2016-12-01

    Six children with Attention Deficit Hyperactivity Disorder (ADHD) and five control children between the ages of 9 and 11 years were administered an adapted version of the Iowa Gambling Task while measuring anticipatory electrodermal response (EDR). Anticipatory EDR measures were compared between groups. Results indicate that the ADHD group exhibited significantly lower autonomic reactivity to anticipated consequences, evidencing a neuropsychological profile similar to patients with lesions in the ventromedial prefrontal cortex.

  4. 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

  5. CART neurons in the arcuate nucleus and lateral hypothalamic area exert differential controls on energy homeostasis.

    Science.gov (United States)

    Lau, Jackie; Farzi, Aitak; Qi, Yue; Heilbronn, Regine; Mietzsch, Mario; Shi, Yan-Chuan; Herzog, Herbert

    2018-01-01

    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. 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. 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 Cart cre/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 Arc CART ;Cart cre/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 LHA CART ;Cart cre/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). Taken together, these results identify catabolic and anabolic effects of CART in the Arc and LHA, respectively, demonstrating for the first time the distinct and region

  6. Presynaptic control of nociceptor signalling: Differential influence of Mu Opioid and GABAergic Systems

    Directory of Open Access Journals (Sweden)

    Ruth C Riley

    2000-01-01

    Full Text Available The relative contribution of pre- and postsynaptic controls to the flow of nociceptive information at the level of the spinal cord has been one of Ron Melzack's longstanding interests and a key issue in the formulation of the gate control theory. The authors review their own studies, in which they monitored internalization of the neurokinin-1 receptor to examine specifically the action of two classically inhibitory systems - mu opioid and gamma-amino butyric acid (GABA - on noxious stimulus-evoked tachykinin signalling in the rat spinal cord. Evidence that opioids and GABAergic controls operate differently on the central consequences of any noxious stimulus-induced substance P release is provided. Whereas at least 80% of the tachykinin signalling remained intact after even the highest concentration of spinal morphine or D-Ala2, NMe-phe4, Glyol5-enkephalin administration, spinal administration of the GABAB receptor agonist baclofen had a dramatic inhibitory effect. These findings are discussed in light of the disappointing clinical utility of baclofen and neurokinin-1 receptor antagonists to combat pain.

  7. Leukocyte DNA methylation signature differentiates pancreatic cancer patients from healthy controls.

    Directory of Open Access Journals (Sweden)

    Katrina S Pedersen

    2011-03-01

    Full Text Available Pancreatic adenocarcinoma (PaC is one of most difficult tumors to treat. Much of this is attributed to the late diagnosis. To identify biomarkers for early detection, we examined DNA methylation differences in leukocyte DNA between PaC cases and controls in a two-phase study. In phase I, we measured methylation levels at 1,505 CpG sites in treatment-naïve leukocyte DNA from 132 never-smoker PaC patients and 60 never-smoker healthy controls. We found significant differences in 110 CpG sites (false discovery rate <0.05. In phase II, we tested and validated 88 of 96 phase I selected CpG sites in 240 PaC cases and 240 matched controls (p≤0.05. Using penalized logistic regression, we built a prediction model consisting of five CpG sites (IL10_P348, LCN2_P86, ZAP70_P220, AIM2_P624, TAL1_P817 that discriminated PaC patients from controls (C-statistic = 0.85 in phase I; 0.76 in phase II. Interestingly, one CpG site (LCN2_P86 alone could discriminate resectable patients from controls (C-statistic= 0.78 in phase I; 0.74 in phase II. We also performed methylation quantitative trait loci (methQTL analysis and identified three CpG sites (AGXT_P180_F, ALOX12_E85_R, JAK3_P1075_R where the methylation levels were significantly associated with single nucleotide polymorphisms (SNPs (false discovery rate <0.05. Our results demonstrate that epigenetic variation in easily obtainable leukocyte DNA, manifested by reproducible methylation differences, may be used to detect PaC patients. The methylation differences at certain CpG sites are partially attributable to genetic variation. This study strongly supports future epigenome-wide association study using leukocyte DNA for biomarker discovery in human diseases.

  8. Rapid evolution leads to differential population dynamics and top-down control in resurrectedDaphniapopulations.

    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.

  9. Metabolic Pathway Signatures Associated with Urinary Metabolite Biomarkers Differentiate Bladder Cancer Patients from Healthy Controls.

    Science.gov (United States)

    Kim, Won Tae; Yun, Seok Joong; Yan, Chunri; Jeong, Pildu; Kim, Ye Hwan; Lee, Il Seok; Kang, Ho Won; Park, Sunghyouk; Moon, Sung Kwon; Choi, Yung Hyun; Choi, Young Deuk; Kim, Isaac Yi; Kim, Jayoung; Kim, Wun Jae

    2016-07-01

    Our previous high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry study identified bladder cancer (BCA)-specific urine metabolites, including carnitine, acylcarnitines, and melatonin. The objective of the current study was to determine which metabolic pathways are perturbed in BCA, based on our previously identified urinary metabolome. A total of 135 primary BCA samples and 26 control tissue samples from healthy volunteers were analyzed. The association between specific urinary metabolites and their related encoding genes was analyzed. Significant alterations in the carnitine-acylcarnitine and tryptophan metabolic pathways were detected in urine specimens from BCA patients compared to those of healthy controls. The expression of eight genes involved in the carnitine-acylcarnitine metabolic pathway (CPT1A, CPT1B, CPT1C, CPT2, SLC25A20, and CRAT) or tryptophan metabolism (TPH1 and IDO1) was assessed by RT-PCR in our BCA cohort (n=135). CPT1B, CPT1C, SLC25A20, CRAT, TPH1, and IOD1 were significantly downregulated in tumor tissues compared to normal bladder tissues (pmetabolic pathways, which were the most perturbed pathways in BCA, were determined.

  10. 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

  11. 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.

  12. Controlling Self-Renewal and Differentiation of Stem Cells via Mechanical Cues

    Science.gov (United States)

    Nava, Michele M.; Raimondi, Manuela T.; Pietrabissa, Riccardo

    2012-01-01

    The control of stem cell response in vitro, including self-renewal and lineage commitment, has been proved to be directed by mechanical cues, even in the absence of biochemical stimuli. Through integrin-mediated focal adhesions, cells are able to anchor onto the underlying substrate, sense the surrounding microenvironment, and react to its properties. Substrate-cell and cell-cell interactions activate specific mechanotransduction pathways that regulate stem cell fate. Mechanical factors, including substrate stiffness, surface nanotopography, microgeometry, and extracellular forces can all have significant influence on regulating stem cell activities. In this paper, we review all the most recent literature on the effect of purely mechanical cues on stem cell response, and we introduce the concept of “force isotropy” relevant to cytoskeletal forces and relevant to extracellular loads acting on cells, to provide an interpretation of how the effects of insoluble biophysical signals can be used to direct stem cells fate in vitro. PMID:23091358

  13. Differential action for ethanol on baroreceptor reflex control of heart rate and sympathetic efferent discharge in rats

    Energy Technology Data Exchange (ETDEWEB)

    Xin, Z.; Abdel-Rahman, A.R.A.; Wooles, W.R.

    1988-01-01

    The acute effects of ethanol (0.33, 0.66, or 1 g/kg) on baroreflex control of heart rate (HR) and sympathetic efferent discharge (SED) were investigated in rats. The two higher doses of ethanol caused a progressive and significant increase in baseline SED and a slight increase in HR. The findings suggest that the sensitivity of the reflex control of SED was preserved whereas that of HR was impaired after acute ethanol administration. Since these findings were obtained in the same animals, the data suggest that acute ethanol has a differential action on reflex control of SED and HR. Further, the significant increase in SED after moderate and high doses of ethanol suggests an increased central sympathetic tone as recordings were made from preganglionic nerve fibers (splanchnic nerve). The absence of an increase in baseline MAP, in spite of a significant increase in baseline SED following acute ethanol injection, could be explained, at least in part, by an ethanol-evoked reduction in pressor responsiveness to phenylephrine, an ..cap alpha..-adrenergic agonist.

  14. Differential impact of the cheese matrix on the postprandial lipid response: a randomized, crossover, controlled trial.

    Science.gov (United States)

    Drouin-Chartier, Jean-Philippe; Tremblay, André J; Maltais-Giguère, Julie; Charest, Amélie; Guinot, Léa; Rioux, Laurie-Eve; Labrie, Steve; Britten, Michel; Lamarche, Benoît; Turgeon, Sylvie L; Couture, Patrick

    2017-12-01

    Background: In a simulated gastrointestinal environment, the cheese matrix modulates dairy fat digestion. However, to our knowledge, the impact of the cheese matrix on postprandial lipemia in humans has not yet been evaluated. Objective: In healthy subjects, we compared the impact of dairy fat provided from firm cheese, soft cream cheese, and butter on the postprandial response at 4 h and on the incremental area under the curve (iAUC) of plasma triglycerides. Design: Forty-three healthy subjects were recruited to this randomized, crossover, controlled trial. In random order at intervals of 14 d and after a 12-h fast, subjects ingested 33 g fat from a firm cheese (young cheddar), a soft cream cheese (cream cheese), or butter (control) incorporated into standardized meals that were matched for macronutrient content. Plasma concentrations of triglycerides were measured immediately before the meal and 2, 4, 6, and 8 h after the meal. Results: Cheddar cheese, cream cheese, and butter induced similar increases in triglyceride concentrations at 4 h (change from baseline: +59%, +59%, and +62%, respectively; P = 0.9). No difference in the triglyceride iAUC 0-8 h ( P -meal = 0.9) was observed between the 3 meals. However, at 2 h, the triglyceride response caused by the cream cheese (change from baseline: +44%) was significantly greater than that induced by butter (change from baseline: +24%; P = 0.002) and cheddar cheese (change from baseline: +16%; P = 0.0004). At 6 h, the triglyceride response induced by cream cheese was significantly attenuated compared with that induced by cheddar cheese (change from baseline: +14% compared with +42%; P = 0.0004). Conclusion: This study demonstrates that the cheese matrix modulates the impact of dairy fat on postprandial lipemia in healthy subjects. This trial was registered at clinicaltrials.gov as NCT02623790. © 2017 American Society for Nutrition.

  15. Expression, purification and preliminary X-ray analysis of the Neisseria meningitidis outer membrane protein PorB

    Energy Technology Data Exchange (ETDEWEB)

    Tanabe, Mikio; Iverson, Tina M.; (Vanderbilt)

    2010-01-28

    The Neisseria meningitidis outer membrane protein PorB was expressed in Escherichia coli and purified from inclusion bodies by denaturation in urea followed by refolding in buffered LDAO on a size-exclusion column. PorB has been crystallized in three different crystal forms: C222, R32 and P6{sub 3}. The C222 crystal form may contain either one or two PorB monomers in the asymmetric unit, while both the R32 and P6{sub 3} crystal forms contained one PorB monomer in the asymmetric unit. Of the three, the P6{sub 3} crystal form had the best diffraction quality, yielding data extending to 2.3 {angstrom} resolution.

  16. 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

  17. 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

  18. 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.

  19. Opa+ and Opa- isolates of Neisseria meningitidis and Neisseria gonorrhoeae induce sustained proliferative responses in human CD4+ T cells.

    Science.gov (United States)

    Youssef, Abdel-Rahman; van der Flier, Michiel; Estevão, Silvia; Hartwig, Nico G; van der Ley, Peter; Virji, Mumtaz

    2009-11-01

    T cells may interact with a number of bacterial surface antigens, an encounter which has the potential to downmodulate host immune responses. Neisseria meningitidis, a human colonizer and an agent of septicemia and meningitis, expresses Opa proteins which interact with the CEACAM1 receptor expressed on activated T cells. Since CEACAM1 can act as an inhibitory receptor and T cells in subepithelial tissues may encounter whole bacteria, which often express Opa proteins in vivo, this study assessed primarily if Opa proteins expressed on meningococci affect T-cell functions. In addition, Opa-containing outer membrane vesicles (OMV) have been used as vaccine antigens, and therefore Opa+ and Opa- OMV were also studied. While Opa+ bacteria adhered to CEACAM-expressing T cells, both the Opa+ and Opa- phenotypes induced no to a small transient depression, followed by a prolonged increase in proliferation as well as cytokine production. Such responses were also observed with heat-killed bacteria or OMV. In addition, while anti-CEACAM antibodies alone inhibited proliferation, on coincubation of T cells with bacteria and the antibodies, bacterial effects predominated and were Opa independent. Thus, while Opa proteins of N. meningitidis can bind to T-cell-expressed CEACAM1, this is not sufficient to overcome the T-cell recognition of bacterial factors, which results in a proliferative and cytokine response, an observation consistent with the ability of the host to establish lasting immunity to Opa-expressing meningococci that it frequently encounters. The data also imply that Opa-proficient vaccine preparations may not necessarily inhibit T-cell functions via CEACAM1 binding.

  20. Differential interactions between Notch and ID factors control neurogenesis by modulating Hes factor autoregulation.

    Science.gov (United States)

    Boareto, Marcelo; Iber, Dagmar; Taylor, Verdon

    2017-10-01

    During embryonic and adult neurogenesis, neural stem cells (NSCs) generate the correct number and types of neurons in a temporospatial fashion. Control of NSC activity and fate is crucial for brain formation and homeostasis. Neurogenesis in the embryonic and adult brain differ considerably, but Notch signaling and inhibitor of DNA-binding (ID) factors are pivotal in both. Notch and ID factors regulate NSC maintenance; however, it has been difficult to evaluate how these pathways potentially interact. Here, we combined mathematical modeling with analysis of single-cell transcriptomic data to elucidate unforeseen interactions between the Notch and ID factor pathways. During brain development, Notch signaling dominates and directly regulates Id4 expression, preventing other ID factors from inducing NSC quiescence. Conversely, during adult neurogenesis, Notch signaling and Id2/3 regulate neurogenesis in a complementary manner and ID factors can induce NSC maintenance and quiescence in the absence of Notch. Our analyses unveil key molecular interactions underlying NSC maintenance and mechanistic differences between embryonic and adult neurogenesis. Similar Notch and ID factor interactions may be crucial in other stem cell systems. © 2017. Published by The Company of Biologists Ltd.

  1. Biomimetic nanocomposites to control osteogenic differentiation of human mesenchymal stem cells.

    Science.gov (United States)

    Liao, Susan; Nguyen, Luong T H; Ngiam, Michelle; Wang, Charlene; Cheng, Ziyuan; Chan, Casey K; Ramakrishna, Seeram

    2014-05-01

    The design of biomimetic nanomaterials that can directly influence the behavior of cells and facilitate the regeneration of tissues and organs has become an active area of research. Here, the production of materials based on nano-hydroxyapatite composites in scaffolds with nanofibrous and nanoporous topographies, designed to mimic the native bone matrix for applications in bone tissue engineering, is reported. Human mesenchymal stem cells grown on these nanocomposites are stimulated to rapidly produce bone minerals in situ, even in the absence of osteogenic supplements in the cell-culture medium. Nanocomposites comprising type I collagen and nano-hydroxyapatite are found to be especially efficient at inducing mineralization. When subcutaneously implanted into nude mice, this biomimetic nanocomposite is able to form a new bone matrix within only two weeks. Furthermore, when the nanocomposite is enriched with human mesenchymal stem cells before implantation, development of the bone matrix is accelerated to within one week. To the best of the authors' knowledge, this study provides the first clear in vitro and in vivo demonstration of osteoinduction controlled by the material characteristics of a biomimetic nanocomposite. This approach can potentially facilitate the translation of de novo bone-formation technologies to the clinic. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  2. GATA4-dependent organ-specific endothelial differentiation controls liver development and embryonic hematopoiesis.

    Science.gov (United States)

    Géraud, Cyrill; Koch, Philipp-Sebastian; Zierow, Johanna; Klapproth, Kay; Busch, Katrin; Olsavszky, Victor; Leibing, Thomas; Demory, Alexandra; Ulbrich, Friederike; Diett, Miriam; Singh, Sandhya; Sticht, Carsten; Breitkopf-Heinlein, Katja; Richter, Karsten; Karppinen, Sanna-Maria; Pihlajaniemi, Taina; Arnold, Bernd; Rodewald, Hans-Reimer; Augustin, Hellmut G; Schledzewski, Kai; Goerdt, Sergij

    2017-03-01

    Microvascular endothelial cells (ECs) are increasingly recognized as organ-specific gatekeepers of their microenvironment. Microvascular ECs instruct neighboring cells in their organ-specific vascular niches through angiocrine factors, which include secreted growth factors (angiokines), extracellular matrix molecules, and transmembrane proteins. However, the molecular regulators that drive organ-specific microvascular transcriptional programs and thereby regulate angiodiversity are largely elusive. In contrast to other ECs, which form a continuous cell layer, liver sinusoidal ECs (LSECs) constitute discontinuous, permeable microvessels. Here, we have shown that the transcription factor GATA4 controls murine LSEC specification and function. LSEC-restricted deletion of Gata4 caused transformation of discontinuous liver sinusoids into continuous capillaries. Capillarization was characterized by ectopic basement membrane deposition, formation of a continuous EC layer, and increased expression of VE-cadherin. Correspondingly, ectopic expression of GATA4 in cultured continuous ECs mediated the downregulation of continuous EC-associated transcripts and upregulation of LSEC-associated genes. The switch from discontinuous LSECs to continuous ECs during embryogenesis caused liver hypoplasia, fibrosis, and impaired colonization by hematopoietic progenitor cells, resulting in anemia and embryonic lethality. Thus, GATA4 acts as master regulator of hepatic microvascular specification and acquisition of organ-specific vascular competence, which are indispensable for liver development. The data also establish an essential role of the hepatic microvasculature in embryonic hematopoiesis.

  3. Differential baroreflex control of heart rate in sedentary and aerobically fit individuals

    Science.gov (United States)

    Smith, S. A.; Querry, R. G.; Fadel, P. J.; Welch-O'Connor, R. M.; Olivencia-Yurvati, A.; Shi, X.; Raven, P. B.

    2000-01-01

    PURPOSE: We compared arterial, aortic, and carotid-cardiac baroreflex sensitivity in eight average fit (maximal oxygen uptake, VO2max = 42.2+/-1.9 mL x kg(-1) x min(-1)) and eight high fit (VO2max = 61.9+/-2.2 mL x kg(-1) x min(-1)) healthy young adults. METHODS: Arterial and aortic (ABR) baroreflex functions were assessed utilizing hypo- and hyper-tensive challenges induced by graded bolus injections of sodium nitroprusside (SN) and phenylephrine (PE), respectively. Carotid baroreflex (CBR) sensitivity was determined using ramped 5-s pulses of both pressure and suction delivered to the carotid sinus via a neck chamber collar, independent of drug administration. RESULTS: During vasoactive drug injection, mean arterial pressure (MAP) was similarly altered in average fit (AF) and high fit (HF) groups. However, the heart rate (HR) response range of the arterial baroreflex was significantly attenuated (P baroreflex response range was significantly less than the simple sum of the CBR and ABR (HF, 38+/-3 beats x min(-1) and AF, 57+/-4 beats x min(-1)) in both fitness groups. CONCLUSIONS: These data confirm that reductions in arterial-cardiac reflex sensitivity are mediated by diminished ABR function. More importantly, these data suggest that the integrative relationship between the ABR and CBR contributing to arterial baroreflex control of HR is inhibitory in nature and not altered by exercise training.

  4. MEK1 and MEK2 differentially control the duration and amplitude of the ERK cascade response

    International Nuclear Information System (INIS)

    Kocieniewski, Pawel; Lipniacki, Tomasz

    2013-01-01

    The Raf/MEK/ERK cascade is one of the most studied and important signal transduction pathways. However, existing models largely ignore the existence of isoforms of the constituent kinases and their interactions. Here, we propose a model of the ERK cascade that includes heretofore neglected differences between isoforms of MEK. In particular, MEK1 is subject to a negative feedback from activated ERK, which is further conferred to MEK2 via hetero-dimerization. Specifically, ERK phosphorylates MEK1 at the residue Thr292, hypothetically creating an additional phosphatase binding site, accelerating MEK1 and MEK2 dephosphorylation. We incorporated these recently discovered interactions into a mathematical model of the ERK cascade that reproduces the experimental results of Catalanotti et al (2009 Nature Struct. Mol. Biol. 16 294–303) and Kamioka et al (2010 J. Biol. Chem. 285 33540–8). Furthermore, the model allows for predictions regarding the differences in the catalytic activity and function of the MEK isoforms. We propose that the MEK1/MEK2 ratio regulates the duration of the response, which increases with the level of MEK2 and decreases with the level of MEK1. In turn, the amplitude of the response is controlled by the total amount of the two isoforms. We confirm the proposed model structure performing a random parameter sampling, which led us to the conclusion that the sampled parameters, selected to properly reproduce wild-type (WT) cell behavior, to allow for qualitative reproduction of differences in behavior WT cells and cell mutants studied experimentally. (paper)

  5. MEK1 and MEK2 differentially control the duration and amplitude of the ERK cascade response

    Science.gov (United States)

    Kocieniewski, Pawel; Lipniacki, Tomasz

    2013-06-01

    The Raf/MEK/ERK cascade is one of the most studied and important signal transduction pathways. However, existing models largely ignore the existence of isoforms of the constituent kinases and their interactions. Here, we propose a model of the ERK cascade that includes heretofore neglected differences between isoforms of MEK. In particular, MEK1 is subject to a negative feedback from activated ERK, which is further conferred to MEK2 via hetero-dimerization. Specifically, ERK phosphorylates MEK1 at the residue Thr292, hypothetically creating an additional phosphatase binding site, accelerating MEK1 and MEK2 dephosphorylation. We incorporated these recently discovered interactions into a mathematical model of the ERK cascade that reproduces the experimental results of Catalanotti et al (2009 Nature Struct. Mol. Biol. 16 294-303) and Kamioka et al (2010 J. Biol. Chem. 285 33540-8). Furthermore, the model allows for predictions regarding the differences in the catalytic activity and function of the MEK isoforms. We propose that the MEK1/MEK2 ratio regulates the duration of the response, which increases with the level of MEK2 and decreases with the level of MEK1. In turn, the amplitude of the response is controlled by the total amount of the two isoforms. We confirm the proposed model structure performing a random parameter sampling, which led us to the conclusion that the sampled parameters, selected to properly reproduce wild-type (WT) cell behavior, to allow for qualitative reproduction of differences in behavior WT cells and cell mutants studied experimentally.

  6. Differential control of abdominal muscles during multi-directional support-surface translations in man.

    Science.gov (United States)

    Carpenter, Mark G; Tokuno, Craig D; Thorstensson, Alf; Cresswell, Andrew G

    2008-07-01

    The current study aimed to understand how deep and superficial abdominal muscles are coordinated with respect to activation onset times and amplitudes in response to unpredictable support-surface translations delivered in multiple directions. Electromyographic (EMG) data were recorded intra-muscularly using fine-wire electrodes inserted into the right rectus abdominis (RA), obliquus externus (OE), obliquus internus (OI) and transversus abdominis (TrA) muscles. Twelve young healthy male subjects were instructed to maintain their standing balance during 40 support surface translations (peak acceleration 1.3 m s(-2); total displacement 0.6 m) that were counter-balanced between four different directions (forward, backward, leftward, rightward). Differences between abdominal muscles in EMG onset times were found for specific translation directions. The more superficial RA (backward translations) and OE (forward and leftward translations) muscles had significantly earlier EMG onsets compared to TrA. EMG onset latencies were dependent on translation direction in RA, OE and OI, but independent of direction in TrA. EMG amplitudes in RA and OE were dependent on translation direction within the first 100 ms of activity, whereas responses from the two deeper muscles (TrA and OI) were independent of translation direction during this interval. The current results provide new insights into how abdominal muscles contribute to postural reactions during human stance. Response patterns of deep and superficial abdominal muscles during support surface translations are unlike those previously described during upper-body perturbations or voluntary arm movements, indicating that the neural mechanisms controlling individual abdominal muscles are task-specific to different postural demands.

  7. Genetic Differentiation in Native and Introduced Populations of Cryptolaemus montrouzieri (Coleoptera: Coccinellidae) and Its Implications for Biological Control Programs.

    Science.gov (United States)

    Li, Hao-Sen; Jin, Meng-Jie; Ślipiński, Adam; De Clercq, Patrick; Pang, Hong

    2015-10-01

    Cryptolaemus montrouzieri Mulsant (Coleoptera: Coccinellidae) is an effective biological control agent of Australian origin, which has been introduced worldwide to control mealybugs. Although successfully used for >100 yr, its introduction in a new area may cause environmental risks should the populations become invasive. In the present study, a population genetics method was used to make predictions of the invasive potential of C. montrouzieri. Our results showed a similar level of genetic diversity among all populations. No significant genetic differentiation between native and introduced populations was observed, while three populations from the native region were significantly divergent. The fact that genetic diversity was not reduced in introduced areas suggests that no bottleneck effect has occurred during introduction. To avoid rapid evolution of the introduced C. montrouzieri, the introduction records of each population should be clearly traced and introductions from multiple sources into the same area should be avoided. © The Authors 2015. Published by Oxford University Press on behalf of Entomological Society of America. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  8. 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

  9. 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.

  10. Biophysical Attributes of CpG Presentation Control TLR9 Signaling to Differentially Polarize Systemic Immune Responses

    Directory of Open Access Journals (Sweden)

    Jardin A. Leleux

    2017-01-01

    Full Text Available It is currently unknown whether and how mammalian pathogen recognition receptors (PRRs respond to biophysical patterns of pathogen-associated molecular danger signals. Using synthetic pathogen-like particles (PLPs that mimic physical properties of bacteria or large viruses, we have discovered that the quality and quantity of Toll-like receptor 9 (TLR9 signaling by CpG in mouse dendritic cells (mDCs are uniquely dependent on biophysical attributes; specifically, the surface density of CpG and size of the presenting PLP. These physical patterns control DC programming by regulating the kinetics and magnitude of MyD88-IRAK4 signaling, NF-κB-driven responses, and STAT3 phosphorylation, which, in turn, controls differential T cell responses and in vivo immune polarization, especially T helper 1 (Th1 versus T helper 2 (Th2 antibody responses. Our findings suggest that innate immune cells can sense and respond not only to molecular but also pathogen-associated physical patterns (PAPPs, broadening the tools for modulating immunity and helping to better understand innate response mechanisms to pathogens and develop improved vaccines.

  11. Use of sodC versus ctrA for real-time polymerase chain reaction-based detection of Neisseria meningitidis in sterile body fluids

    Directory of Open Access Journals (Sweden)

    Fábio Takenori Higa

    2013-04-01

    Full Text Available We evaluated the use of a newly described sodC-based real-time-polymerase chain reaction (RT-PCR assay for detecting Neisseria meningitidis in normally sterile sites, such as cerebrospinal fluid and serum. The sodC-based RT-PCR assay has an advantage over ctrA for detecting nongroupable N. meningitidis isolates, which are commonly present in asymptomatic pharyngeal carriage. However, in our study, sodC-based RT-PCR was 7.5% less sensitive than ctrA. Given the public health impact of possible false-negative results due to the use of the sodC target gene alone, sodC-based RT-PCR for the diagnosis of meningococcal meningitis should be used with caution.

  12. Detection of bacterial DNA in cerebrospinal fluid by an assay for simultaneous detection of Neisseria meningitidis, Haemophilus influenzae, and streptococci using a seminested PCR strategy.

    OpenAIRE

    Rådström, P; Bäckman, A; Qian, N; Kragsbjerg, P; Påhlson, C; Olcén, P

    1994-01-01

    Primers specific to conserved and variable regions in the 16S rRNA sequence were selected from the partially sequenced 16S rRNA genes of Neisseria meningitidis, Haemophilus influenzae, Streptococcus pneumoniae, S. agalactiae, and Staphylococcus epidermidis. The PCR assay was divided into two DNA amplifications. The first resulted in a general bacterial amplicon, and the second resulted in a species-specific amplicon. The high specificity of the PCR assay was documented after testing bacteria ...

  13. Respuesta inmune sistémica y mucosal contra Neisseria meningitidis B inducida por estrategia de vacunación simultánea mucosal y parental

    Directory of Open Access Journals (Sweden)

    González E

    2009-08-01

    Full Text Available mmunization is one of the most successful and cost-effective health interventions ever. Immunization have been helping to reduce child mortality, improving maternal health and combating infectious diseases. In spite of its, undisputed past success and promising future, however, immunization remains an unfinished agenda because of them inadequate coverage. Several factors have been largely responsible of a difficulty to attain immunization coverage and have been recognized as a problems of current vaccines, such as: the number of dose, excessive use of parenteral route, a small number of adjuvants approve for use in human, higher reactogenicity and unavailability against intracellular pathogens, infected or altered cells and scanty feasibility to combined more than one antigen in the same formulation. For bacterial meningitis WHO estimates that 1.2 million cases occur annually and Neisseria meningitidis is the etiological agent in more than 40% of these cases although some meningococcal vaccines are available. To bear in mind these principals problems, a novel protocol for vaccination against N. meningitidis called Single Time Vaccination Strategy (SinTimVaS is proposed. Using female BALB/c mice, we induce systemic and mucosal immune responses against N. meningitidis with only one parenteral and one mucosal dose at the same time, employing the Finlay Adjuvants derivate from N. meningitidis, AFPL1 and AFCo1, respectively. In conclusion, SinTimVaS could increase the vaccination coverage and reduce the time-cost of vaccine campaigns, adding the possibility to increase the herd immunity by mucosal specific response induction.

  14. 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. Copyright © 2016

  15. 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

  16. Unravelling the differential functions and regulation of striatal neuron sub-populations in motor control, reward and motivational processes

    Directory of Open Access Journals (Sweden)

    Sabrina eEna

    2011-07-01

    Full Text Available The striatum, the major input structure of the basal ganglia, is critically involved in motor control and learning of habits and skills, and is also involved in motivational and reward processes. The dorsal striatum, caudate-putamen, is primarily implicated in motor functions whereas the ventral striatum, the nucleus accumbens, is essential for motivation and drug reinforcement. Severe basal ganglia dysfunction occurs in movement disorders as Parkinson’s and Huntington’s disease, and in psychiatric disorders such as schizophrenia and drug addiction. The striatum is essentially composed of GABAergic medium-sized spiny neurons (MSNs that are output neurons giving rise to the so-called direct and indirect pathways and are targets of the cerebral cortex and mesencephalic dopaminergic neurons. Although the involvement of striatal sub-areas in motor control and motivation has been thoroughly characterized, major issues remained concerning the specific and respective functions of the two MSNs sub-populations, D2R-striatopallidal (dopamine D2 receptor-positive and D1R-striatonigral (dopamine D1 receptor-positive neurons, as well as their specific regulation. Here, we review recent advances that gave new insight in the understanding of the differential roles of striatopallidal and striatonigral neurons in the basal ganglia circuit. We discuss innovative techniques developed in the last decade which allowed a much precise evaluation of molecular pathways implicated in motivational processes and functional roles of striatopallidal and striatonigral neurons in motor control and in the establishment of reward-associated behaviour.

  17. Polysaccharide production in batch process of Neisseria meningitidis serogroup C comparing Frantz, modified Frantz and Cartlin 6 cultivation media Produção de polissacarídeo em processo de cultivo descontínuo de Neisseria meningitidis sorogrupo C comparando os meios de cultivo Frantz, Frantz modificado e Catlin 6

    Directory of Open Access Journals (Sweden)

    Marcelo Fossa da Paz

    2003-04-01

    Full Text Available Polysaccharide of N. meningitidis serogroup C constitutes the antigen for the vaccine against meningitis. The goal of this work was to compare three cultivation media for production of this polysaccharide: Frantz, modified Frantz medium (with replacement of glucose by glycerol, and Catlin 6 (a synthetic medium with glucose. The comparative criteria were based on the final polysaccharide concentrations and the yield coefficient cell/polysaccharide (Y P/X. The kinetic parameters: pH, substrate consumption and cell growth were also determined. For this purpose, 9 cultivation runs were carried out in a 80 L New Brunswick bioreactor, under the following conditions: 42 L of culture medium, temperature 35ºC, air flow 5 L/min, agitation frequency 120 rpm and vessel pressure 6 psi, without dissolved oxygen or pH controls. The cultivation runs were divided in three groups, with 3 repetitions each. The cultivation using the Frantz medium presented the best results: average of final polysaccharide concentration = 0.134 g/L and Y P/X=0.121, followed by Catlin 6 medium, with results of 0.095 g/L and 0.067 respectively. Considering the principal advantages in the use of the synthetic medium, i.e. facilitation of a cultivation and purification steps of the polysaccharide production process, there is a possibility that in the near future, Catlin 6 will replace the traditional Frantz medium.O polissacarídeo de N. meningitidis sorogrupo C constitui o antígeno para a elaboração da vacina contra a meningite C. O objetivo deste trabalho foi comparar três meios de cultivo para produção desse polissacarídeo: Frantz, Frantz modificado (com a substituição de glicose por glicerol e Catlin 6 (meio sintético com glicose. Os critérios comparativos foram baseados nas concentrações finais de polissacarídeo e o fator de conversão célula/polissacarídeo (Y P/X. Também foram determinados os parâmetros cinéticos de pH, consumo de substrato e crescimento

  18. Meningococcal Neonatal Purulent Conjunctivitis/Sepsis and Asymptomatic Carriage of N. meningitidis in Mother’s Vagina and Both Parents’ Nasopharynx

    Directory of Open Access Journals (Sweden)

    Enrique Chacon-Cruz

    2017-01-01

    Full Text Available Neonatal conjunctivitis is usually associated with vagina’s infection by Chlamydia sp., N. gonorrhoeae, and/or other bacteria during delivery. Meningococcal neonatal conjunctivitis is an extremely rare disease. We report a case of neonatal meningococcal sepsis/conjunctivitis and asymptomatic carriage of N. meningitidis from both parents (vagina and nasopharynx. As part of our active surveillance for meningococcal disease at the Tijuana General Hospital (TGH, Mexico, we identified a 3-day-old newborn with meningococcal conjunctivitis and sepsis. The patient had a one-day history of conjunctivitis and poor feeding. Clinical examination confirmed profuse purulent conjunctival discharge, as well as clinical signs and laboratory findings suggestive of bacteraemia. Gram stain from conjunctival exudate revealed intracellular Gram negative diplococci; we presumed the baby had gonorrheal conjunctivitis; however, serogroup Y, N. meningitidis was isolated both from conjunctival exudate and blood. Additionally, isolation of serogroup Y, N. meningitidis was obtained from mother’s vagina and both parents’ nasopharynx. The baby was treated with 7 days of IV ceftriaxone and discharged with no sequelae.

  19. Different cytokine production and Toll-like receptor expression induced by heat-killed invasive and carrier strains of Neisseria meningitidis.

    Science.gov (United States)

    Potmesil, Roman; Beran, Ondrej; Musilek, Martin; Kriz, Pavla; Holub, Michal

    2014-01-01

    Neisseria meningitidis may cause severe invasive disease. The carriage state of the pathogen is common, and the reasons underlying why the infection becomes invasive are not fully understood. The aim of this study was to compare the differences between invasive and carrier strains in the activation of innate immunity. The monocyte expression of TLR2, TLR4, CD14, and HLA-DR, cytokine production, and the granulocyte oxidative burst were analyzed after in vitro stimulation by heat-killed invasive (n = 14) and carrier (n = 9) strains of N. meningitidis. The expression of the cell surface markers in monocytes, the oxidative burst, and cytokine concentrations were measured using flow cytometry. Carrier strains stimulated a higher production of inflammatory cytokines and oxidative burst in granulocytes than invasive strains (all p < 0.001), whereas invasive strains significantly up-regulated TLR2, TLR4 (p < 0.001), and CD14 (p < 0.01) expression on monocytes. Conversely, the monocyte expression of HLA-DR was higher after the stimulation by carrier strains (p < 0.05) in comparison to invasive strains. The LPS inhibitor polymyxin B abolished the differences between the strains. Our findings indicate different immunostimulatory potencies of invasive strains of N. meningitidis compared with carrier strains. © 2013 APMIS Published by Blackwell Publishing Ltd.

  20. A distal intergenic region controls pancreatic endocrine differentiation by acting as a transcriptional enhancer and as a polycomb response element.

    Directory of Open Access Journals (Sweden)

    Joris van Arensbergen

    Full Text Available Lineage-selective expression of developmental genes is dependent on the interplay between activating and repressive mechanisms. Gene activation is dependent on cell-specific transcription factors that recognize transcriptional enhancer sequences. Gene repression often depends on the recruitment of Polycomb group (PcG proteins, although the sequences that underlie the recruitment of PcG proteins, also known as Polycomb response elements (PREs, remain poorly understood in vertebrates. While distal PREs have been identified in mammals, a role for positive-acting enhancers in PcG-mediated repression has not been described. Here we have used a highly efficient procedure based on lentiviral-mediated transgenesis to carry out in vivo fine-mapping of, cis-regulatory sequences that control lineage-specific activation of Neurog3, a master regulator of pancreatic endocrine differentiation. Our findings reveal an enhancer region that is sufficient to drive correct spacio-temporal expression of Neurog3 and demonstrate that this same region serves as a PRE in alternative lineages where Neurog3 is inactive.

  1. Bootstrapping of gene-expression data improves and controls the false discovery rate of differentially expressed genes

    Directory of Open Access Journals (Sweden)

    Goddard Mike E

    2004-03-01

    Full Text Available Abstract The ordinary-, penalized-, and bootstrap t-test, least squares and best linear unbiased prediction were compared for their false discovery rates (FDR, i.e. the fraction of falsely discovered genes, which was empirically estimated in a duplicate of the data set. The bootstrap-t-test yielded up to 80% lower FDRs than the alternative statistics, and its FDR was always as good as or better than any of the alternatives. Generally, the predicted FDR from the bootstrapped P-values agreed well with their empirical estimates, except when the number of mRNA samples is smaller than 16. In a cancer data set, the bootstrap-t-test discovered 200 differentially regulated genes at a FDR of 2.6%, and in a knock-out gene expression experiment 10 genes were discovered at a FDR of 3.2%. It is argued that, in the case of microarray data, control of the FDR takes sufficient account of the multiple testing, whilst being less stringent than Bonferoni-type multiple testing corrections. Extensions of the bootstrap simulations to more complicated test-statistics are discussed.

  2. 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}.

  3. 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.

  4. 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.

  5. 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.

  6. G1/S Inhibitors and the SWI/SNF Complex Control Cell-Cycle Exit during Muscle Differentiation

    NARCIS (Netherlands)

    Ruijtenberg, Suzan; van den Heuvel, Sander

    2015-01-01

    The transition from proliferating precursor cells to post-mitotic differentiated cells is crucial for development, tissue homeostasis, and tumor suppression. To study cell-cycle exit during differentiation in vivo, we developed a conditional knockout and lineage-tracing system for Caenorhabditis

  7. Mimicking the neurotrophic factor profile of embryonic spinal cord controls the differentiation potential of spinal progenitors into neuronal cells.

    Directory of Open Access Journals (Sweden)

    Masaya Nakamura

    Full Text Available Recent studies have indicated that the choice of lineage of neural progenitor cells is determined, at least in part, by environmental factors, such as neurotrophic factors. Despite extensive studies using exogenous neurotrophic factors, the effect of endogenous neurotrophic factors on the differentiation of progenitor cells remains obscure. Here we show that embryonic spinal cord derived-progenitor cells express both ciliary neurotrophic factor (CNTF and brain-derived neurotrophic factor (BDNF mRNA before differentiation. BDNF gene expression significantly decreases with their differentiation into the specific lineage, whereas CNTF gene expression significantly increases. The temporal pattern of neurotrophic factor gene expression in progenitor cells is similar to that of the spinal cord during postnatal development. Approximately 50% of spinal progenitor cells differentiated into astrocytes. To determine the effect of endogenous CNTF on their differentiation, we neutralized endogenous CNTF by administration of its polyclonal antibody. Neutralization of endogenous CNTF inhibited the differentiation of progenitor cells into astrocytes, but did not affect the numbers of neurons or oligodendrocytes. Furthermore, to mimic the profile of neurotrophic factors in the spinal cord during embryonic development, we applied BDNF or neurotrophin (NT-3 exogenously in combination with the anti-CNTF antibody. The exogenous application of BDNF or NT-3 promoted the differentiation of these cells into neurons or oligodendrocytes, respectively. These findings suggest that endogenous CNTF and exogenous BDNF and NT-3 play roles in the differentiation of embryonic spinal cord derived progenitor cells into astrocytes, neurons and oligodendrocytes, respectively.

  8. Identification of differentially expressed genes using an annealing control primer system in stage III serous ovarian carcinoma

    International Nuclear Information System (INIS)

    Kim, Yun-Sook; Hwan Do, Jin; Bae, Sumi; Bae, Dong-Han; Shick Ahn, Woong

    2010-01-01

    Most patients with ovarian cancer are diagnosed with advanced stage disease (i.e., stage III-IV), which is associated with a poor prognosis. Differentially expressed genes (DEGs) in stage III serous ovarian carcinoma compared to normal tissue were screened by a new differential display method, the annealing control primer (ACP) system. The potential targets for markers that could be used for diagnosis and prognosis, for stage III serous ovarian cancer, were found by cluster and survival analysis. The ACP-based reverse transcriptase polymerase chain reaction (RT PCR) technique was used to identify DEGs in patients with stage III serous ovarian carcinoma. The DEGs identified by the ACP system were confirmed by quantitative real-time PCR. Cluster analysis was performed on the basis of the expression profile produced by quantitative real-time PCR and survival analysis was carried out by the Kaplan-Meier method and Cox proportional hazards multivariate model; the results of gene expression were compared between chemo-resistant and chemo-sensitive groups. A total of 114 DEGs were identified by the ACP-based RT PCR technique among patients with stage III serous ovarian carcinoma. The DEGs associated with an apoptosis inhibitory process tended to be up-regulated clones while the DEGs associated with immune response tended to be down-regulated clones. Cluster analysis of the gene expression profile obtained by quantitative real-time PCR revealed two contrasting groups of DEGs. That is, a group of genes including: SSBP1, IFI6 DDT, IFI27, C11orf92, NFKBIA, TNXB, NEAT1 and TFG were up-regulated while another group of genes consisting of: LAMB2, XRCC6, MEF2C, RBM5, FOXP1, NUDCP2, LGALS3, TMEM185A, and C1S were down-regulated in most patients. Survival analysis revealed that the up-regulated genes such as DDAH2, RNase K and TCEAL2 might be associated with a poor prognosis. Furthermore, the prognosis of patients with chemo-resistance was predicted to be very poor when genes such

  9. 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.

  10. 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

  11. Co-ordinate action of bacterial adhesins and human carcinoembryonic antigen receptors in enhanced cellular invasion by capsulate serum resistant Neisseria meningitidis.

    Science.gov (United States)

    Rowe, Helen A; Griffiths, Natalie J; Hill, Darryl J; Virji, Mumtaz

    2007-01-01

    Neisseria meningitidis (Nm) is a human specific opportunistic pathogen that occasionally penetrates mucosal barriers via the action of adhesins and invasins and evades host immune mechanisms during further dissemination via capsule expression. From in vitro studies, the primary adhesion of capsulate bacteria is believed to be mediated by polymeric pili, followed by invasion via outer membrane adhesins such as Opa proteins. As the latter requires the surface capsule to be down-modulated, invading bacteria would be serum sensitive and thus avirulent. However, there is recent evidence that capsulate bacteria may interact via Opa proteins when host cells express high levels of carcinoembryonic antigen-related cell adhesion molecules (CEACAMs), their target receptors. Such a situation may arise following increased circulation of inflammatory cytokines that upregulate certain adhesion molecules on host cells. In this study, using a tetracycline controlled expression system, we have developed cell lines with inducible CEACAM expression to mimic post-inflammation state of target tissues and analysed the interplay between the three surface components capsule, pili and Opa proteins in cellular interactions. With two distinct cell lines, not only the level but also the rate of adhesion of capsulate Opa-expressing Nm increased concurrently with CEACAM density. Moreover, when threshold levels of receptor were reached, cellular invasion ensued in an Opa-dependent manner. In studies with cell lines intrinsically expressing pilus receptors, notable synergism in cellular interactions between pili and Opa of several meningococcal strains was observed and was independent of capsule type. A number of internalized bacteria were shown to express capsule and when directly isolated from host cells, these bacteria were as serum resistant as the inoculated phenotype. Furthermore, we observed that agents that block Opa-CEACAM binding substantially reduced cellular invasion, while maintaining

  12. Caracterización fenotípica de cepas invasivas de Neisseria meningitidis aisladas en Cuba durante 20 años

    Directory of Open Access Journals (Sweden)

    Isabel Martínez

    2006-04-01

    Full Text Available Se investigaron los marcadores epidemiológicos (serogrupos, serotipos, subtipos, inmunotipos de 429 cepas invasivas, aisladas en Cuba durante 20 años (1982-2002. Basándonos en el comportamiento de la incidencia de la Enfermedad Meningocócica (EM en el período investigado, las cepas se distribuyeron en dos etapas: epidémica y postepidémica. La epidémica, comprendió 279 cepas aisladas entre 1982-1992 y la ostepidémica, incluyó 150 aislamientos pertenecientes al período comprendido entre 1993-2002. Todas se cultivaron en Agar Mueller Hinton con suero fetal bovino (5% y se incubaron 24-48 horas, 37 0C, en atmósfera húmeda con 5% de C02. La identificación de género, especie y serogrupo, se realizó mediante métodos convencionales; para la caracterización de los sero/subtipos e inmunotipos, se utilizó el ensayo inmunoenzimático (ELISA de células enteras con anticuerpos monoclonales. En ambas etapas predominó el serogrupo B (97,90%: epidémica (96,77% y postepidémica (100%. Sin embargo, el serogrupo C (1,43% y cepas no agrupables (1,8%, sólo se observaron en aislamientos de la etapa epidémica. Los otros marcadores prevalentes fueron: serotipo 4 (86,48%, subtipo P1.19,15 (78,32%, inmunotipo L3,7,9 (90,2% , todos mostraron cifras similares en ambos períodos.Predominó el fenotipo B:4:P1.19,15:L3,7,9 (69,69%, aunque, en la etapa postepidémica (77,34%, el porcentaje fue superior al de la etapa epidémica (65,66% (p<0,05; además, en las cepas de este período, se observó una mayor diversidad de asociaciones fenotípicas. Los resultados obtenidos de esta caracterización fenotípica de las cepas de Neisseria meningitidis aisladas de enfermos aporta datos valiosos al estudio, prevención y control exitoso de la EM en Cuba.

  13. 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.

  14. 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.

  15. DIGIT Is a Conserved Long Noncoding RNA that Regulates GSC Expression to Control Definitive Endoderm Differentiation of Embryonic Stem Cells

    Directory of Open Access Journals (Sweden)

    Kaveh Daneshvar

    2016-10-01

    Full Text Available Long noncoding RNAs (lncRNAs exhibit diverse functions, including regulation of development. Here, we combine genome-wide mapping of SMAD3 occupancy with expression analysis to identify lncRNAs induced by activin signaling during endoderm differentiation of human embryonic stem cells (hESCs. We find that DIGIT is divergent to Goosecoid (GSC and expressed during endoderm differentiation. Deletion of the SMAD3-occupied enhancer proximal to DIGIT inhibits DIGIT and GSC expression and definitive endoderm differentiation. Disruption of the gene encoding DIGIT and depletion of the DIGIT transcript reveal that DIGIT is required for definitive endoderm differentiation. In addition, we identify the mouse ortholog of DIGIT and show that it is expressed during development and promotes definitive endoderm differentiation of mouse ESCs. DIGIT regulates GSC in trans, and activation of endogenous GSC expression is sufficient to rescue definitive endoderm differentiation in DIGIT-deficient hESCs. Our study defines DIGIT as a conserved noncoding developmental regulator of definitive endoderm.

  16. Clonal Distribution of Disease-Associated and Healthy Carrier Isolates of Neisseria meningitidis between 1983 and 2005 in Cuba ▿

    Science.gov (United States)

    Climent, Yanet; Yero, Daniel; Martinez, Isabel; Martín, Alejandro; Jolley, Keith A.; Sotolongo, Franklin; Maiden, Martin C. J.; Urwin, Rachel; Pajón, Rolando

    2010-01-01

    In response to epidemic levels of serogroup B meningococcal disease in Cuba during the 1980s, the VA-MENGOC-BC vaccine was developed and introduced into the National Infant Immunization Program in 1991. Since then the incidence of meningococcal disease in Cuba has returned to the low levels recorded before the epidemic. A total of 420 Neisseria meningitidis strains collected between 1983 and 2005 in Cuba were analyzed by multilocus sequence typing (MLST). The set of strains comprised 167 isolated from disease cases and 253 obtained from healthy carriers. By MLST analysis, 63 sequence types (STs) were identified, and 32 of these were reported to be a new ST. The Cuban isolates were associated with 12 clonal complexes; and the most common were ST-32 (246 isolates), ST-53 (86 isolates), and ST-41/44 (36 isolates). This study also showed that the application of VA-MENGOC-BC, the Cuban serogroup B and C vaccine, reduced the frequency and diversity of hypervirulent clonal complexes ST-32 (vaccine serogroup B type-strain) and ST-41/44 and also affected other lineages. Lineages ST-8 and ST-11 were no longer found during the postvaccination period. The vaccine also affected the genetic composition of the carrier-associated meningococcal isolates. The number of carrier isolates belonging to hypervirulent lineages decreased significantly after vaccination, and ST-53, a sequence type common in carriers, became the predominant ST. PMID:20042619

  17. Whole-Genome Characterization of Epidemic Neisseria meningitidis Serogroup C and Resurgence of Serogroup W, Niger, 2015

    Science.gov (United States)

    Kretz, Cecilia B.; Retchless, Adam C.; Sidikou, Fati; Issaka, Bassira; Ousmane, Sani; Schwartz, Stephanie; Tate, Ashley H.; Pana, Assimawè; Njanpop-Lafourcade, Berthe-Marie; Nzeyimana, Innocent; Nse, Ricardo Obama; Deghmane, Ala-Eddine; Hong, Eva; Brynildsrud, Ola Brønstad; Novak, Ryan T.; Meyer, Sarah A.; Oukem-Boyer, Odile Ouwe Missi; Ronveaux, Olivier; Caugant, Dominique A.; Taha, Muhamed-Kheir

    2016-01-01

    In 2015, Niger reported the largest epidemic of Neisseria meningitidis serogroup C (NmC) meningitis in sub-Saharan Africa. The NmC epidemic coincided with serogroup W (NmW) cases during the epidemic season, resulting in a total of 9,367 meningococcal cases through June 2015. To clarify the phylogenetic association, genetic evolution, and antibiotic determinants of the meningococcal strains in Niger, we sequenced the genomes of 102 isolates from this epidemic, comprising 81 NmC and 21 NmW isolates. The genomes of 82 isolates were completed, and all 102 were included in the analysis. All NmC isolates had sequence type 10217, which caused the outbreaks in Nigeria during 2013–2014 and for which a clonal complex has not yet been defined. The NmC isolates from Niger were substantially different from other NmC isolates collected globally. All NmW isolates belonged to clonal complex 11 and were closely related to the isolates causing recent outbreaks in Africa. PMID:27649262

  18. Dinámicas de las interacciones de Neisseria meningitidis con las barreras celulares y los efectores inmunes

    Directory of Open Access Journals (Sweden)

    Natalie J. Griffiths

    2009-08-01

    Full Text Available Neisseria meningitidis outer membrane (OM adhesins, Opa and Opc are known to exert significant influence on bacterial adhesion and invasion properties. They are also likely to affect the dynamics of cellular barrier penetration as they target human receptors that are subject to upregulation under inflammatory conditions. As some of the targeted receptors are also expressed on immune cells, it is possible that the OM proteins, when presented on bacteria or in OM vesicle vaccines, have the additional capacity to modulate host immune responses. In our recent studies, in vitro model systems were used to further explore these possibilities. The studies illustrated that the major human receptors targeted by Opa and Opc, i.e. CEACAMs and integrins, when upregulated by inflammatory cytokines, encourage enhanced cellular adhesion, invasion and barrier traversal. Tissue infiltration by fully capsulate bacteria via Opa proteins was also observed for piliated Opa+ meningococci. Other studies indicate that Opc increases meningococcal resistance to serum-mediated killing by binding to the complement regulatory molecule vitronectin. In addition, although adverse immunomodulatory effects have been reported for Opa-expressing gonococci and meningococcal OMVs, our studies indicate that interactions with CD4+ T cell expressed CEACAM1 does not offer immunomodulatory properties to meningococci.

  19. Genetic diversity and levels of expression of factor H binding protein among carriage isolates of Neisseria meningitidis.

    Directory of Open Access Journals (Sweden)

    Ludovic Lemée

    Full Text Available The prevention of meningococcal disease may be improved by recombinant vaccines such as 4CMenB and rLP2086 that target the factor H binding protein (fHbp, an immunogenic surface component of Neisseria meningitidis present as one of three variants. Whether such vaccines decrease carriage of invasive isolates and thus induce herd immunity is unknown. We analyzed the genetic diversity and levels of expression of fHbp among 268 carriage strains and compare them to those of 467 invasive strains. fhbp gene sequencing showed higher proportions of variants 2 and 3 among carriage isolates (p<0.0001. Carriage isolates expressed lower levels of fHbp (p<0.01 but that remain high enough to predict targeting by antibodies against fHbp particularly in group B isolates belonging to the frequent hypervirulent clonal complexes in Europe and North America (cc32, cc41/44, cc269. This suggests that fHbp targeting meningococcal vaccines might reduce, at least in part, the acquisition of some hyperinvasive isolates.

  20. Meningococcal Disease Caused by Neisseria meningitidis Serogroup B Serotype 4 in São Paulo, Brazil, 1990 to 1996

    Directory of Open Access Journals (Sweden)

    Sacchi Claudio Tavares

    1998-01-01

    Full Text Available A large epidemic of serogroup B meningococcal disease (MD, has been occurring in greater São Paulo, Brazil, since 1988.21 A Cuban-produced vaccine, based on outer-membrane-protein (OMP from serogroup B: serotype 4: serosubtype P1.15 (B:4:P1.15 Neisseria meningitidis, was given to about 2.4 million children aged from 3 months to 6 years during 1989 and 1990. The administration of vaccine had little or no measurable effects on this outbreak. In order to detect clonal changes that could explain the continued increase in the incidence of disease after the vaccination, we serotyped isolates recovered between 1990 and 1996 from 834 patients with systemic disease. Strains B:4:P1.15, which was detected in the area as early as 1977, has been the most prevalent phenotype since 1988. These strains are still prevalent in the area and were responsible for about 68% of 834 serogroup B cases in the last 7 years. We analyzed 438 (52% of these strains by restriction fragment length polymorphism (RFLPs of rRNA genes (ribotyping. The most frequent pattern obtained was referred to as Rb1 (68%. We concluded that the same clone of B:4:P1.15-Rb1 strains was the most prevalent strain and responsible for the continued increase of incidence of serogroup B MD cases in greater São Paulo during the last 7 years in spite of the vaccination trial.

  1. Gene variability and degree of expression of vaccine candidate factor H binding protein in clinical isolates of Neisseria meningitidis.

    Science.gov (United States)

    Kelly, Anne; Jacobsson, Susanne; Hussain, Shahida; Olcén, Per; Mölling, Paula

    2013-01-01

    The factor H binding protein (fHbp) is currently being evaluated in clinical trials as a vaccine candidate for a meningococcal group B vaccine. We have previously described the prevalence and sequence variation of fHbp (Jacobsson et al., 2009) and here we investigate the expression of the antigen. The present study includes isolates from carriers (n = 62) and patients with invasive Neisseria meningitidis infections (n = 146), of which 62 had a fatal outcome. Among the invasive isolates from patients with fatal and non-fatal infections fHbp allele 1 was most common (42% and 29% respectively), but it was only identified in 3% of the carrier isolates, where allele 16 was most frequent (13%). The Fluorescence-activated cell sorting analysis identified fHbp expression in all except seven isolates and further analysis by Western blot showed that five of these seven samples were indeed negative using a polyclonal anti-fHbp serum. The negative isolates belonged to serogroup B fHbp allele 24, Y allele 104, and W-135 allele 16 (all invasive). Two were non-serogroupable carrier isolates (allele 21 and 101). An interesting finding is that isolates from invasive infections with fatal outcome had lower expression of fHbp or lower affinity for the fHbp antibody compared to isolates from non-fatal invasive infections and carriers. © 2012 The Authors APMIS © 2012 APMIS.

  2. Pilot study of laser induced breakdown spectroscopy for tissue differentiation by monitoring the plume created during laser surgery — An approach on a feedback Laser control mechanism

    Energy Technology Data Exchange (ETDEWEB)

    Kanawade, Rajesh, E-mail: Rajesh.Kanawade@aot.uni-erlangen.de [Clinical Photonics Lab, Erlangen Graduate School in Advanced Optical Technologies (SAOT), Friedrich-Alexander-Universität Erlangen-Nürnberg, Paul-Gordan-Str. 6, 91052 Erlangen (Germany); Institute of Photonics Technologies, Friedrich-Alexander-Universität Erlangen-Nürnberg, Paul-Gordan-Str. 3, 91052 Erlangen (Germany); Mehari, Fanuel [Master Programme in Advanced Optical Technologies (MAOT), Friedrich-Alexander-Universität Erlangen-Nürnberg, Paul-Gordan-Str. 6, 91052 Erlangen (Germany); Knipfer, Christian; Rohde, Maximilian [Department of Oral and Maxillofacial Surgery, University Hospital Erlangen, Friedrich-Alexander-Universität Erlangen-Nürnberg, Glueckstrasse 11, 91054 Erlangen (Germany); Tangermann-Gerk, Katja [Bayerisches Laserzentrum GmbH, Konrad-Zuse-Strasse 2-6, 91052 Erlangen (Germany); Schmidt, Michael [Clinical Photonics Lab, Erlangen Graduate School in Advanced Optical Technologies (SAOT), Friedrich-Alexander-Universität Erlangen-Nürnberg, Paul-Gordan-Str. 6, 91052 Erlangen (Germany); Institute of Photonics Technologies, Friedrich-Alexander-Universität Erlangen-Nürnberg, Paul-Gordan-Str. 3, 91052 Erlangen (Germany); Bayerisches Laserzentrum GmbH, Konrad-Zuse-Strasse 2-6, 91052 Erlangen (Germany); and others

    2013-09-01

    This study focuses on tissue differentiation using ‘Laser Induced Breakdown Spectroscopy’ (LIBS) by monitoring the plasma plume created during laser surgery processes. This technique is aimed at controlling a laser surgery feedback system in real time. An Excimer laser (Ar-F 193 nm) was used for the ablation of tissue samples. Fat, muscle, nerve and skin tissue samples of bisected ex-vivo pig heads were prepared as test objects for the ablation procedure. A single fiber was used to collect emissions and deliver them to a spectrometer. The obtained LIBS spectra in the measured emissions were analyzed to determine each tissue type according to their chemical composition. The elements found in the samples and their emission spectra were in agreement with those described in literature. The collected LIBS spectra were analyzed to differentiate the tissues using statistical data analysis: Principal Component Analysis (PCA), Linear Discriminant Analysis (LDA) and Receiver Operating Characteristics (ROC). The obtained preliminary results suggest a successful differentiation of the target tissues with high sensitivity and specificity. The main goal of this study was to qualitatively identify tissue types during laser ablation, which will provide a real time feedback mechanism for clinical Laser surgery applications to significantly improve the accuracy and safety of laser surgery procedures. - Graphical abstract: Skin, fat, muscle and nerve tissue differentiation. - Highlights: • Methods to differentiate tissues for the application in a laser surgery feedback control system • Successful differentiation of the target tissues with high sensitivity and specificity for laser surgery application • Real time feedback mechanism for clinical Laser surgery applications • Laser surgery requirements • Biomedical applications of LIBS.

  3. 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...

  4. New proteoliposome vaccine formulation from N. meningitidis serogroup B, without aluminum hydroxide, retains its antimeningococcal protectogenic potential as well as Th-1 adjuvant capacity.

    Science.gov (United States)

    Tamargo, Beatriz; Márquez, Yanet; Ramírez, Wendy; Cedré, Bárbara; Fresno, Manuel; Sierra, Gustavo

    2013-01-01

    Proteoliposomes purified from the Outer Membrane of Neisseria meningitidis B, have been successfully used as core for adjuvants and vaccine formulations. We have tried to increase their structural definition and to conserve their efficacy and stability avoiding the addition of the aluminum hydroxide to the final formulation. Liposomal particle systems were prepared from components of defined molecular structure, such as a Neisseria meningitidis B protein complex, extracted and purified without forming vesicle structures. Liposomes were prepared from a mixture of dioleoyl phosphatidyl serine and cholesterol, using the classical dehydration-rehydration method. Transmission Electron Microscopy (TEM) was used to characterize the liposomes. BALB/c mice were used for animal testing procedures. Analysis of specific IgG response, serum bactericidal activity as well as DTH reaction was carried out. Isolation and purification of mRNA and real-time PCR, was performed to determine the dominating Th lymphokine pattern. The new antimeningococcal formulation without aluminum hydroxide prepared with components of defined molecular structure assembled itself into Neoproteoliposomes (NPL) ranging from 50 to 70 nm in diameter. The extraction and purification of selected membrane proteins to provide the antigen for this new formulation (PD-Tp), as well as the NPL-formulation favors a Th1 response pattern, suggested by the higher percentages of DTH, increased expression of proinflamatory lymphokine mRNAs when administered by intramuscular and intranasal routes. It stimulates a systemic bactericidal antibody response against Neisseria meningitidis B and immunologic memory similar to the Cuban VA-MENGOC-BC vaccine, even at lower dosages and is less reactogenic at the injection site in comparison with the formulation with aluminum hydroxide. This new adjuvant formulation could be applicable to the development of new and improved vaccines against meningococcal disease, and eventually as

  5. Bacterial meningitis epidemiology and return of Neisseria meningitidis serogroup A cases in Burkina Faso in the five years following MenAfriVac mass vaccination campaign.

    Directory of Open Access Journals (Sweden)

    Alpha Oumar Diallo

    Full Text Available Historically, Neisseria meningitidis serogroup A (NmA caused large meningitis epidemics in sub-Saharan Africa. In 2010, Burkina Faso became the first country to implement a national meningococcal serogroup A conjugate vaccine (MACV campaign. We analyzed nationwide meningitis surveillance data from Burkina Faso for the 5 years following MACV introduction.We examined Burkina Faso's aggregate reporting and national laboratory-confirmed case-based meningitis surveillance data from 2011-2015. We calculated incidence (cases per 100,000 persons, and described reported NmA cases.In 2011-2015, Burkina Faso reported 20,389 cases of suspected meningitis. A quarter (4,503 of suspected meningitis cases with cerebrospinal fluid specimens were laboratory-confirmed as either S. pneumoniae (57%, N. meningitidis (40%, or H. influenzae (2%. Average adjusted annual national incidence of meningococcal meningitis was 3.8 (range: 2.0-10.2 annually and was highest among infants aged <1 year (8.4. N. meningitidis serogroup W caused the majority (64% of meningococcal meningitis among all age groups. Only six confirmed NmA cases were reported in 2011-2015. Five cases were in children who were too young (n = 2 or otherwise not vaccinated (n = 3 during the 2010 MACV mass vaccination campaign; one case had documented MACV receipt, representing the first documented MACV failure.Meningococcal meningitis incidence in Burkina Faso remains relatively low following MACV introduction. However, a substantial burden remains and NmA transmission has persisted. MACV integration into routine childhood immunization programs is essential to ensure continued protection.

  6. Bacterial meningitis epidemiology and return of Neisseria meningitidis serogroup A cases in Burkina Faso in the five years following MenAfriVac mass vaccination campaign.

    Science.gov (United States)

    Diallo, Alpha Oumar; Soeters, Heidi M; Yameogo, Issaka; Sawadogo, Guetawendé; Aké, Flavien; Lingani, Clément; Wang, Xin; Bita, Andre; Fall, Amadou; Sangaré, Lassana; Ouédraogo-Traoré, Rasmata; Medah, Isaïe; Bicaba, Brice; Novak, Ryan T

    2017-01-01

    Historically, Neisseria meningitidis serogroup A (NmA) caused large meningitis epidemics in sub-Saharan Africa. In 2010, Burkina Faso became the first country to implement a national meningococcal serogroup A conjugate vaccine (MACV) campaign. We analyzed nationwide meningitis surveillance data from Burkina Faso for the 5 years following MACV introduction. We examined Burkina Faso's aggregate reporting and national laboratory-confirmed case-based meningitis surveillance data from 2011-2015. We calculated incidence (cases per 100,000 persons), and described reported NmA cases. In 2011-2015, Burkina Faso reported 20,389 cases of suspected meningitis. A quarter (4,503) of suspected meningitis cases with cerebrospinal fluid specimens were laboratory-confirmed as either S. pneumoniae (57%), N. meningitidis (40%), or H. influenzae (2%). Average adjusted annual national incidence of meningococcal meningitis was 3.8 (range: 2.0-10.2 annually) and was highest among infants aged <1 year (8.4). N. meningitidis serogroup W caused the majority (64%) of meningococcal meningitis among all age groups. Only six confirmed NmA cases were reported in 2011-2015. Five cases were in children who were too young (n = 2) or otherwise not vaccinated (n = 3) during the 2010 MACV mass vaccination campaign; one case had documented MACV receipt, representing the first documented MACV failure. Meningococcal meningitis incidence in Burkina Faso remains relatively low following MACV introduction. However, a substantial burden remains and NmA transmission has persisted. MACV integration into routine childhood immunization programs is essential to ensure continued protection.

  7. Differential impact of a Dutch alcohol prevention program targeting adolescents and parents separately and simultaneously: low self-control and lenient parenting at baseline predict effectiveness.

    Science.gov (United States)

    Koning, Ina M; Verdurmen, Jacqueline E E; Engels, Rutger C M E; van den Eijnden, Regina J J M; Vollebergh, Wilma A M

    2012-06-01

    To test whether baseline levels of the factors accountable for the impact of the Prevention of Alcohol use in Students (PAS) intervention (self-control, perceived rules about alcohol and parental attitudes about alcohol), moderate the effect of the intervention. A cluster randomized trial including 3,490 Dutch early adolescents (M age=12.66, SD=.49) and their parents randomized over four conditions: 1) parent intervention, 2) student intervention, 3) combined intervention and 4) control group. Moderators at baseline were used to examine the differential effects of the interventions on onset of (heavy) weekly drinking at 34-month follow-up. The combined intervention was only effective in preventing weekly drinking among those adolescents who reported to have lower self-control and more lenient parents at baseline. No differential effect was found for the onset of heavy weekly drinking. No moderating roles of self-control and lenient parenting were found for the separate student and parent interventions regarding the onset of drinking. The combined intervention is more effective among adolescents with low-self control and lenient parents at baseline, both factors that were a specific target of the intervention. The relevance of targeting self-control in adolescents and restrictive parenting is underlined.

  8. Gibberellin-Regulation and Genetic Variations in Leaf Elongation for Tall Fescue in Association with Differential Gene Expression Controlling Cell Expansion.

    Science.gov (United States)

    Xu, Qian; Krishnan, Sanalkumar; Merewitz, Emily; Xu, Jichen; Huang, Bingru

    2016-07-26

    Leaf elongation rate (LER) is an important factor controlling plant growth and productivity. The objective of this study was to determine whether genetic variation in LER for a fast-growing ('K-31'), and a dwarf cultivar ('Bonsai') of tall fescue (Festuca arundinacea) and gibberellic acid (GA) regulation of LER were associated with differential expression of cell-expansion genes. Plants were treated with GA3, trinexapac-ethyl (TE) (GA inhibitor), or water (untreated control) in a hydroponic system. LER of 'K-31' was 63% greater than that of 'Bonsai', which corresponded with 32% higher endogenous GA4 content in leaf and greater cell elongation and production rates under the untreated control condition. Exogenous application of GA3 significantly enhanced LER while TE treatment inhibited leaf elongation due to GA3-stimulation or TE-inhibition of cell elongation and production rate in leaves for both cultivars. Real-time quantitative polymerase chain reaction analysis revealed that three α-expansins, one β-expansin, and three xyloglucan endotransglycosylase (XET) genes were associated with GA-stimulation of leaf elongation, of which, the differential expression of EXPA4 and EXPA7 was related to the genotypic variation in LER of two cultivars. Those differentially-expressed expansin and XET genes could play major roles in genetic variation and GA-regulated leaf elongation in tall fescue.

  9. Inhibition of the dapE-Encoded N-Succinyl-L,L-diaminopimelic Acid Desuccinylase from Neisseria meningitidis by L-Captopril

    OpenAIRE

    Starus, Anna; Nocek, Boguslaw; Bennett, Brian; Larrabee, James A.; Shaw, Daniel L.; Sae-Lee, Wisath; Russo, Marie T.; Gillner, Danuta M.; Makowska-Grzyska, Magdalena; Joachimiak, Andrzej; Holz, Richard C.

    2015-01-01

    Binding of the competitive inhibitor L-captopril to the dapE-encoded N-succinyl-L,L-diaminopimelic acid desuccinylase from Neisseria meningitidis (NmDapE) was examined by kinetic, spectroscopic, and crystallographic methods. L-Captopril, an angiotensin-converting enzyme (ACE) inhibitor, was previously shown to be a potent inhibitor of the DapE from Haemophilus influenzae (HiDapE) with an IC50 of 3.3 μM and a measured Ki of 1.8 μM and displayed a dose-responsive antibiotic activity toward Esch...

  10. Notes from the Field: Increase in Neisseria meningitidis-Associated Urethritis Among Men at Two Sentinel Clinics - Columbus, Ohio, and Oakland County, Michigan, 2015.

    Science.gov (United States)

    Bazan, Jose A; Peterson, Amy S; Kirkcaldy, Robert D; Briere, Elizabeth C; Maierhofer, Courtney; Turner, Abigail Norris; Licon, Denisse B; Parker, Nicole; Dennison, Amanda; Ervin, Melissa; Johnson, Laura; Weberman, Barbara; Hackert, Pamela; Wang, Xin; Kretz, Cecilia B; Abrams, A Jeanine; Trees, David L; Del Rio, Carlos; Stephens, David S; Tzeng, Yih-Ling; DiOrio, Mary; Roberts, Mysheika Williams

    2016-06-03

    Neisseria meningitidis (Nm) urogenital infections, although less common than infections caused by Neisseria gonorrhoeae (Ng), have been associated with urethritis, cervicitis, proctitis, and pelvic inflammatory disease. Nm can appear similar to Ng on Gram stain analysis (gram-negative intracellular diplococci) (1-5). Because Nm colonizes the nasopharynx, men who receive oral sex (fellatio) can acquire urethral Nm infections (1,3,5). This report describes an increase in Nm-associated urethritis in men attending sexual health clinics in Columbus, Ohio, and Oakland County, Michigan.

  11. Portadores de Neisseria meningitidis, caracterización de las cepas aisladas y respuesta inmune basal a VA-MENGOC-BC

    OpenAIRE

    María J. Valdés; Isabel Martínez; Gustavo Sierra; María A. Camaraza; Iván Cuevas; Mayelin Mirabal; Pedro Rodríguez; Yadira Fuentes; Graciela Bolaños; Isabel Villasusa

    2008-01-01

    Con el propósito de conocer la prevalencia de portadores de Neisseria meningitidis en un grupo de adolescentes, los marcadores epidemiológicos de las cepas aisladas, así como los factores de riesgo asociados con el estado de portador y la respuesta inmune basal a VA-MENGOC-BC , se realizó un estudio transversal descriptivo de portadores en 189 estudiantes de 12-19 años de un politécnico de Ciego de Ávila, siguiendo las Normas Bioéticas establecidas. A los estudiantes se les realizó un exudado...

  12. 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

  13. 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

  14. The interface between transcriptional and epigenetic control of effector and memory CD8⁺ T-cell differentiation.

    Science.gov (United States)

    Gray, Simon M; Kaech, Susan M; Staron, Matthew M

    2014-09-01

    Immunity to many intracellular pathogens requires the proliferation, differentiation, and function of CD8(+) cytotoxic T lymphocytes (CTLs). While the majority of effector CTLs die upon clearance of the pathogen, a small proportion of them survive to become long-lived memory CTLs. Memory CTLs can provide protective immunity against re-exposure to the same pathogen and are the principle motivation behind T-cell- based vaccine design. While a large body of cellular immunologic research has proven invaluable to define effector and memory CTLs by their different phenotypes and functions, an emerging focus in the field has been to understand how environmental cues regulate CTL differentiation on a genomic level. Genome-wide studies to profile transcriptional and epigenetic changes during infection have revealed that dynamic changes in DNA methylation patterns and histone modifications accompany transcriptional signatures that define and regulate CTL differentiation states. In this review, we emphasize the importance of epigenetic regulation of CD8(+) T-cell differentiation and the likely role that transcription factors play in this process. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  15. The interface between transcriptional and epigenetic control of effector and memory CD8+ T-cell differentiation

    Science.gov (United States)

    Gray, Simon M.; Kaech, Susan M.; Staron, Matthew M.

    2014-01-01

    Summary Immunity to many intracellular pathogens requires the proliferation, differentiation, and function of CD8+ cytotoxic T lymphocytes (CTLs). While the majority of effector CTLs die upon clearance of the pathogen, a small proportion of them survive to become long-lived memory CTLs. Memory CTLs can provide protective immunity against re-exposure to the same pathogen and are the principle motivation behind T-cell- based vaccine design. While a large body of cellular immunologic research has proven invaluable to define effector and memory CTLs by their different phenotypes and functions, an emerging focus in the field has been to understand how environmental cues regulate CTL differentiation on a genomic level. Genome-wide studies to profile transcriptional and epigenetic changes during infection have revealed that dynamic changes in DNA methylation patterns and histone modifications accompany transcriptional signatures that define and regulate CTL differentiation states. In this review, we emphasize the importance of epigenetic regulation of CD8+ T-cell differentiation and the likely role that transcription factors play in this process. PMID:25123283

  16. Distinct nuclear arrangement of active and inactive c-myc genes in control and differentiated colon carcinoma cells

    International Nuclear Information System (INIS)

    Harnicarova, Andrea; Kozubek, Stanislav; Pachernik, Jiri; Krejci, Jana; Bartova, Eva

    2006-01-01

    Using sequential RNA-DNA fluorescence in situ hybridization, the nuclear arrangement of both the active and inactive c-myc gene as well as its transcription was investigated in colon cancer HT-29 cells induced to differentiate into enterocytes. Cytogenetic studies revealed the presence of two chromosomes 8 in HT-29 cells, of which the one containing c-myc gene amplicons was substantially larger and easily distinguished from the normal chromosome. This observation enabled detection of both activity and nuclear localization of c-myc genes in single cells and in individual chromosome territories. Similar transcriptional activity of the c-myc gene was observed in both the normal and derivative chromosome 8 territories showing no influence of the amplification on the c-myc gene expression. Our experiments demonstrate strikingly specific nuclear and territorial arrangements of active genes as compared with inactive ones: on the periphery of their territories facing to the very central region of the cell nucleus. Nuclear arrangement of c-myc genes and transcripts was conserved during cell differentiation and, therefore, independent of the level of differentiation-specific c-myc gene expression. However, after the induction of differentiation, a more internal territorial location was found for the single copy c-myc gene of normal chromosome 8, while amplicons conserved their territorial topography

  17. Systematic optimization of an engineered hydrogel allows for selective control of human neural stem cell survival and differentiation after transplantation in the stroke brain

    Science.gov (United States)

    Moshayedi, Pouria; Nih, Lina R.; Llorente, Irene L.; Berg, Andrew R.; Cinkornpumin, Jessica; Lowry, William E.; Segura, Tatiana; Carmichael, S. Thomas

    2016-01-01

    Stem cell therapies have shown promise in promoting recovery in stroke but have been limited by poor cell survival and differentiation. We have developed a hyaluronic acid (HA)-based self-polymerizing hydrogel that serves as a platform for adhesion of structural motifs and a depot release for growth factors to promote transplant stem cell survival and differentiation. We took an iterative approach in optimizing the complex combination of mechanical, biochemical and biological properties of an HA cell scaffold. First, we optimized stiffness for a minimal reaction of adjacent brain to the transplant. Next hydrogel crosslinkers sensitive to matrix metalloproteinases (MMP) were incorporated as they promoted vascularization. Finally, candidate adhesion motifs and growth factors were systemically changed in vitro using a design of experiment approach to optimize stem cell survival or proliferation. The optimized HA hydrogel, tested in vivo, promoted survival of encapsulated human neural progenitor cells (iPS-NPCs) after transplantation into the stroke core and differentially tuned transplanted cell fate through the promotion of glial, neuronal or immature/progenitor states. This HA hydrogel can be tracked in vivo with MRI. A hydrogel can serve as a therapeutic adjunct in a stem cell therapy through selective control of stem cell survival and differentiation in vivo. PMID:27521617

  18. Prefrontal activation during inhibitory control measured by near-infrared spectroscopy for differentiating between autism spectrum disorders and attention deficit hyperactivity disorder in adults.

    Science.gov (United States)

    Ishii-Takahashi, Ayaka; Takizawa, Ryu; Nishimura, Yukika; Kawakubo, Yuki; Kuwabara, Hitoshi; Matsubayashi, Junko; Hamada, Kasumi; Okuhata, Shiho; Yahata, Noriaki; Igarashi, Takashi; Kawasaki, Shingo; Yamasue, Hidenori; Kato, Nobumasa; Kasai, Kiyoto; Kano, Yukiko

    2014-01-01

    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.

  19. 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.

  20. Mucosal immunization using proteoliposome and cochleate structures from Neisseria meningitidis serogroup B induce mucosal and systemic responses.

    Science.gov (United States)

    Campo, Judith Del; Zayas, Caridad; Romeu, Belkis; Acevedo, Reinaldo; González, Elizabeth; Bracho, Gustavo; Cuello, Maribel; Cabrera, Osmir; Balboa, Julio; Lastre, Miriam

    2009-12-01

    Most pathogens either invade the body or establish infection in mucosal tissues and represent an enormous challenge for vaccine development by the absence of good mucosal adjuvants. A proteoliposome-derived adjuvant from Neisseria meningitidis serogroup B (AFPL1, Adjuvant Finlay Proteoliposome 1) and its derived cochleate form (Co, AFCo1) contain multiple pathogen-associated molecular patterns as immunopotentiators, and can also serve as delivery systems to elicit a Th1-type immune response. The present studies demonstrate the ability of AFPL1and AFCo1 to induce mucosal and systemic immune responses by different mucosal immunizations routes and significant adjuvant activity for antibody responses of both structures: a microparticle and a nanoparticle with a heterologous antigen. Therefore, we used female mice immunized by intragastric, intravaginal, intranasal or intramuscular routes with both structures alone or incorporated with ovalbumin (OVA). High levels of specific IgG antibody were detected in all sera and in vaginal washes, but specific IgA antibody in external secretions was only detected in mucosally immunized mice. Furthermore, antigen specific IgG1 and IgG2a isotypes were all induced. AFPL1 and AFCo1 are capable of inducing IFN-gamma responses, and chemokine secretions, like MIP-1alpha and MIP-1beta. However, AFCo1 is a better alternative to induce immune responses at mucosal level. Even when we use a heterologous antigen, the AFCo1 response was better than with AFPL1 in inducing mucosal and systemic immune responses. These results support the use of AFCo1 as a potent Th1 inducing adjuvant particularly suitable for mucosal immunization.