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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. Neisseria meningitidis rifampicin resistant strains: analysis of protein differentially expressed

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    Schininà Maria

    2010-09-01

    Full Text Available Abstract Background Several mutations have been described as responsible for rifampicin resistance in Neisseria meningitidis. However, the intriguing question on why these strains are so rare remains open. The aim of this study was to investigate the protein content and to identify differential expression in specific proteins in two rifampicin resistant and one susceptible meningococci using two-dimensional electrophoresis (2-DE combined with mass spectrometry. Results In our experimental conditions, able to resolve soluble proteins with an isoelectric point between 4 and 7, twenty-three proteins have been found differentially expressed in the two resistant strains compared to the susceptible. Some of them, involved in the main metabolic pathways, showed an increased expression, mainly in the catabolism of pyruvate and in the tricarboxylic acid cycle. A decreased expression of proteins belonging to gene regulation and to those involved in the folding of polypeptides has also been observed. 2-DE analysis showed the presence of four proteins displaying a shift in their isoelectric point in both resistant strains, confirmed by the presence of amino acid changes in the sequence analysis, absent in the susceptible. Conclusions The analysis of differentially expressed proteins suggests that an intricate series of events occurs in N. meningitidis rifampicin resistant strains and the results here reported may be considered a starting point in understanding their decreased invasion capacity. In fact, they support the hypothesis that the presence of more than one protein differentially expressed, having a role in the metabolism of the meningococcus, influences its ability to infect and to spread in the population. Different reports have described and discussed how a drug resistant pathogen shows a high biological cost for survival and that may also explain why, for some pathogens, the rate of resistant organisms is relatively low considering the

  3. 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.

  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. Outbreak of Neisseria meningitidis C in workers at a large food-processing plant in Brazil: challenges of controlling disease spread to the larger community.

    Science.gov (United States)

    Iser, B P M; Lima, H C A V; de Moraes, C; de Almeida, R P A; Watanabe, L T; Alves, S L A; Lemos, A P S; Gorla, M C O; Gonçalves, M G; Dos Santos, D A; Sobel, J

    2012-05-01

    SUMMARYAn outbreak of meningococcal disease (MD) with severe morbidity and mortality was investigated in midwestern Brazil in order to identify control measures. A MD case was defined as isolation of Neisseria meningitidis, or detection of polysaccharide antigen in a sterile site, or presence of clinical purpura fulminans, or an epidemiological link with a laboratory-confirmed case-patient, between June and August 2008. In 8 out of 16 MD cases studied, serogroup C ST103 complex was identified. Five (31%) cases had neurological findings and five (31%) died. The attack rate was 12 cases/100 000 town residents and 60 cases/100 000 employees in a large local food-processing plant. We conducted a matched case-control study of eight primary laboratory-confirmed cases (1:4). Factors associated with illness in single variable analysis were work at the processing plant [matched odds ratio (mOR) 22, 95% confidence interval (CI) 2·3-207·7, P10 000 plant employees) stopped propagation in the plant, but not in the larger community.

  7. Environmental survival of Neisseria meningitidis.

    Science.gov (United States)

    Tzeng, Y-L; Martin, L E; Stephens, D S

    2014-01-01

    Neisseria meningitidis is transmitted through the inhalation of large human respiratory droplets, but the risk from contaminated environmental surfaces is controversial. Compared to Streptococcus pneumoniae and Acinetobacter baumanni, meningococcal viability after desiccation on plastic, glass or metal surfaces decreased rapidly, but viable meningococci were present for up to 72 h. Encapsulation did not provide an advantage for meningococcal environmental survival on environmental surfaces.

  8. Optimal control of motorsport differentials

    Science.gov (United States)

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

    2015-12-01

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

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  10. Control synchronization of differential mobile robots

    NARCIS (Netherlands)

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

    2004-01-01

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

  11. 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

  12. 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 ...

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

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    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.

  14. 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 convenience isolates from 1965-1985 were available. The increasing prevalence of ciprofloxacin resistance since 2005 in Shanghai was associated with the spread of hypervirulent lineages CC4821 and CC5. Two resistant meningococcal clones ChinaCC4821-R1-C/B and ChinaCC5-R14-A have emerged in Shanghai during the quinolone era. Ciprofloxacin should be utilized with caution for the chemoprophylaxis of N. meningitidis in China.

  15. 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.

  16. 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...

  17. Metabolism and virulence in Neisseria meningitidis

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    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.

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

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    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.

  19. Control of differentiation of melanoma cells

    International Nuclear Information System (INIS)

    Eguchi, Goro

    1980-01-01

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

  20. 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.

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

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    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

  2. The genetic network controlling plasma cell differentiation.

    Science.gov (United States)

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

    2011-10-01

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

  3. 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.

  4. 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.

  5. Genetic diversity of Neisseria meningitidis serogroup C ST-4821 in China based on multiple-locus variable number tandem repeat analysis.

    Directory of Open Access Journals (Sweden)

    Xiaoying Shan

    Full Text Available Neisseria meningitidis sequence type (ST-4821 was first reported in China in 2003, and a new hyper-virulent lineage has been designated as the ST-4821 complex. A large number of N. meningitidis ST-4821 strains have been identified in China since 2003; however, the microevolution characteristics of this complex are unclear. Different combinations of variable number of tandem repeats (VNTR loci were used in multiple-locus VNTR analysis (MLVA to analyze 118 N. meningitidis serogroup C ST-4821 strains isolated from seventeen provinces between 2003 and 2012. Additionally, MLVA with five VNTR loci was performed due to its high discriminatory power. One hundred and eighteen isolates were found to comprise 112 subtypes based on MLVA, and 16 outbreak-associated strains were clustered into one group. These data indicate a high level of diversity for N. meningitidis ST-4821 due to microevolution in the last decade. In addition, the results revealed high similarity between isolates from the same geographic origins, which is helpful when monitoring the spread of N. meningitidis serogroup C ST-4821 and will provide valuable information for the control and prevention of bacterial meningitis in China.

  6. 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.

  7. 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.

  8. 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

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

    African Journals Online (AJOL)

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

  10. 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

  11. 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

  12. Nanotopographical Control of Stem Cell Differentiation

    Directory of Open Access Journals (Sweden)

    Laura E. McNamara

    2010-01-01

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

  13. 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.

  14. Infinite dimensional differential games with hybrid controls

    Indian Academy of Sciences (India)

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

  15. 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...

  16. Laboratory Predictors of Meningococcal Disease And Vaccination in Children: studies on the host immune response against Neisseria meningitidis

    NARCIS (Netherlands)

    C.L. Vermont (Clementien)

    2004-01-01

    markdownabstract__Abstract__ Neisseria meningitidis is a gram-negative diplococcus which was first identified by Anton Weichselbaum in 1887. Strains of N. meningitidis can be classified into serogroups based upon the different composition of its capsular polysaccharide. Thirteen serogroups

  17. Signal differentiation in position tracking control of dc motors

    International Nuclear Information System (INIS)

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

    2015-01-01

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

  18. approximate controllability of a non-autonomous differential equation

    Indian Academy of Sciences (India)

    53

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

  19. 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...

  20. 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.

  1. 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.

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. 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

  7. 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...

  8. 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.

  9. 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.

  10. Global differential geometry: An introduction for control engineers

    Science.gov (United States)

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

    1982-01-01

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

  11. 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

  12. 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.

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

    NARCIS (Netherlands)

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

    2000-01-01

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

  14. 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.

  15. 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.

  16. 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

  17. 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.

  18. 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

  19. 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.

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

    International Nuclear Information System (INIS)

    Goreac, D.

    2009-01-01

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

  1. Neisseria meningitidis presenting as acute abdomen and recurrent reactive pericarditis

    Directory of Open Access Journals (Sweden)

    Karolina Akinosoglou

    2016-11-01

    Full Text Available Meningococcal meningitis is a well established potential fatal infection characterized by fever, headache, petechial rash, and vomiting in the majority of cases. However, protean manifestations including abdominal pain, sore throat, diarrhea and cough, even though rare, should not be overlooked. Similarly, although disseminated infection could potentially involve various organ-targets, secondary immune related complications including joints or pericardium should be dealt with caution, since they remain unresponsive to appropriate antibiotic regimens. We hereby report the rare case of an otherwise healthy adult female, presenting with acute abdominal pain masking Neisseria meningitidis serotype B meningitis, later complicated with recurrent reactive pericarditis despite appropriate antibiotic treatment. There follows a review of current literature.

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

    Science.gov (United States)

    Hunt, L. R.; Villarreal, Ramiro

    1987-01-01

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

  5. 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

  6. 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

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

    Science.gov (United States)

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

    2012-01-01

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

  8. 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

  9. 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

  10. Chaos and its control in an impulsive differential system

    International Nuclear Information System (INIS)

    Jiang Guirong; Lu Qishao; Qian Linning

    2007-01-01

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

  11. Susceptibility to invasive meningococcal disease: polymorphism of complement system genes and Neisseria meningitidis factor H binding protein.

    Directory of Open Access Journals (Sweden)

    Declan T Bradley

    Full Text Available Neisseria meningitidis can cause severe infection in humans. Polymorphism of Complement Factor H (CFH is associated with altered risk of invasive meningococcal disease (IMD. We aimed to find whether polymorphism of other complement genes altered risk and whether variation of N. meningitidis factor H binding protein (fHBP affected the risk association.We undertook a case-control study with 309 European cases and 5,200 1958 Birth Cohort and National Blood Service cohort controls. We used additive model logistic regression, accepting P<0.05 as significant after correction for multiple testing. The effects of fHBP subfamily on the age at infection and severity of disease was tested using the independent samples median test and Student's T test. The effect of CFH polymorphism on the N. meningitidis fHBP subfamily was investigated by logistic regression and Chi squared test.Rs12085435 A in C8B was associated with odds ratio (OR of IMD (0.35 [95% CI 0.19-0.67]; P = 0.03 after correction. A CFH haplotype tagged by rs3753396 G was associated with IMD (OR 0.56 [95% CI 0.42-0.76], P = 1.6x10⁻⁴. There was no bacterial load (CtrA cycle threshold difference associated with carriage of this haplotype. Host CFH haplotype and meningococcal fHBP subfamily were not associated. Individuals infected with meningococci expressing subfamily A fHBP were younger than those with subfamily B fHBP meningococci (median 1 vs 2 years; P = 0.025.The protective CFH haplotype alters odds of IMD without affecting bacterial load for affected heterozygotes. CFH haplotype did not affect the likelihood of infecting meningococci having either fHBP subfamily. The association between C8B rs12085435 and IMD requires independent replication. The CFH association is of interest because it is independent of known functional polymorphisms in CFH. As fHBP-containing vaccines are now in use, relationships between CFH polymorphism and vaccine effectiveness and side-effects may become

  12. [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.

  13. 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.

  14. Effects of multi-walled carbon nanotubes (MWCNT under Neisseria meningitidis transformation process

    Directory of Open Access Journals (Sweden)

    Mattos Ives B

    2011-11-01

    Full Text Available Abstract Background This study aimed at verifying the action of multi-walled carbon nanotubes (MWCNT under the naturally transformable Neisseria meningitidis against two different DNA obtained from isogenic mutants of this microorganism, an important pathogen implicated in the genetic horizontal transfer of DNA, causing the escape of the principal vaccination measured worldwide by the capsular switching process. Materials and methods The bacterium receptor strain C2135 was cultivated and had its mutant DNA donor M2 and M6, which received a receptor strain and MWCNT at three different concentrations. The inhibition effect of DNAse on the DNA in contact with nanoparticles was evaluated. Results The results indicated an in increase in the transformation capacity of N. meninigtidis in different concentrations of MWCNT when compared with negative control without nanotubes. A final analysis of the interaction between DNA and MWCNT was carried out using Raman Spectroscopy. Conclusion These increases in the transformation capacity mediated by MWCNT, in meningococci, indicate the interaction of these particles with the virulence acquisition of these bacteria, as well as with the increase in the vaccination escape process.

  15. 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 serogro......, and as applied in the study MEE was superior to DNA fingerprinting. Clusters of invasive strains were reliably identified by phenotyping alone, whereas determination of identity of carrier strains and an invasive strain required genotyping.......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...

  16. First genome report on novel sequence types of Neisseria meningitidis: ST12777 and ST12778.

    Science.gov (United States)

    Veeraraghavan, Balaji; Lal, Binesh; Devanga Ragupathi, Naveen Kumar; Neeravi, Iyyan Raj; Jeyaraman, Ranjith; Varghese, Rosemol; Paul, Miracle Magdalene; Baskaran, Ashtawarthani; Ranjan, Ranjini

    2018-03-01

    Neisseria meningitidis is an important causative agent of meningitis and/or sepsis with high morbidity and mortality. Baseline genome data on N. meningitidis, especially from developing countries such as India, are lacking. This study aimed to investigate the whole genome sequences of N. meningitidis isolates from a tertiary care centre in India. Whole-genome sequencing was performed using an Ion Torrent™ Personal Genome Machine™ (PGM) with 400-bp chemistry. Data were assembled de novo using SPAdes Genome Assembler v.5.0.0.0. Sequence annotation was performed through PATRIC, RAST and the NCBI PGAAP server. Downstream analysis of the isolates was performed using the Center for Genomic Epidemiology databases for antimicrobial resistance genes and sequence types. Virulence factors and CRISPR were analysed using the PubMLST database and CRISPRFinder, respectively. This study reports the whole genome shotgun sequences of eight N. meningitidis isolates from bloodstream infections. The genome data revealed two novel sequence types (ST12777 and ST12778), along with ST11, ST437 and ST6928. The virulence profile of the isolates matched their sequence types. All isolates were negative for plasmid-mediated resistance genes. To the best of our knowledge, this is the first report of ST11 and ST437 N. meningitidis isolates in India along with two novel sequence types (ST12777 and ST12778). These results indicate that the sequence types circulating in India are diverse and require continuous monitoring. Further studies strengthening the genome data on N. meningitidis are required to understand the prevalence, spread, exact resistance and virulence mechanisms along with serotypes. Copyright © 2017 International Society for Chemotherapy of Infection and Cancer. Published by Elsevier Ltd. All rights reserved.

  17. 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

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

    KAUST Repository

    Stoll, Martin; Wathen, Andy

    2011-01-01

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

  19. 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.

  20. 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

  1. 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.

  2. 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.

  3. Rapid Laboratory Identification of Neisseria meningitidis Serogroup C as the Cause of an Outbreak - Liberia, 2017.

    Science.gov (United States)

    Patel, Jaymin C; George, Josiah; Vuong, Jeni; Potts, Caelin C; Bozio, Catherine; Clark, Thomas A; Thomas, Jerry; Schier, Joshua; Chang, Arthur; Waller, Jessica L; Diaz, Maureen H; Whaley, Melissa; Jenkins, Laurel T; Fuller, Serena; Williams, Desmond E; Redd, John T; Arthur, Ray R; Taweh, Fahn; Vera Walker, Yatta; Hardy, Patrick; Freeman, Maxwell; Katawera, Victoria; Gwesa, Gulu; Gbanya, Miatta Z; Clement, Peter; Kohar, Henry; Stone, Mardia; Fallah, Mosoka; Nyenswah, Tolbert; Winchell, Jonas M; Wang, Xin; McNamara, Lucy A; Dokubo, E Kainne; Fox, LeAnne M

    2017-10-27

    On April 25, 2017, a cluster of unexplained illness and deaths among persons who had attended a funeral during April 21-22 was reported in Sinoe County, Liberia (1). Using a broad initial case definition, 31 cases were identified, including 13 (42%) deaths. Twenty-seven cases were from Sinoe County (1), and two cases each were from Grand Bassa and Monsterrado counties, respectively. On May 5, 2017, initial multipathogen testing of specimens from four fatal cases using the Taqman Array Card (TAC) assay identified Neisseria meningitidis in all specimens. Subsequent testing using direct real-time polymerase chain reaction (PCR) confirmed N. meningitidis in 14 (58%) of 24 patients with available specimens and identified N. meningitidis serogroup C (NmC) in 13 (54%) patients. N. meningitidis was detected in specimens from 11 of the 13 patients who died; no specimens were available from the other two fatal cases. On May 16, 2017, the National Public Health Institute of Liberia and the Ministry of Health of Liberia issued a press release confirming serogroup C meningococcal disease as the cause of this outbreak in Liberia.

  4. 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

  5. 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.

    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

  6. A first meningococcal meningitis case caused by serogroup Ⅹ Neisseria meningitidis strains in China

    Institute of Scientific and Technical Information of China (English)

    CHEN Chao; UANG Ying-chun; ZHANG Tie-gang; HE Jing-guo; WU Jiang; CHEN Li-juan; LIU Jun-feng; PANG Xing-huo; YANG Jie; SHAO Zhu-jun

    2008-01-01

    @@ Neisseria meningitidis is the leading cause of bacterial meningitis and classified into 13 serogroups based on the immunological reactivity of the capsular polysaccharide.1 Serogroups A,B,C,W135 and Y are the most common causes of meningitis.2

  7. 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

  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. 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

  10. Multiple mechanisms of phase variation of PorA in Neisseria meningitidis

    NARCIS (Netherlands)

    van der Ende, A.; Hopman, C. T.; Dankert, J.

    2000-01-01

    Previously, we reported that PorA expression in Neisseria meningitidis is modulated by variation in the length of the homopolymeric tract of guanidine residues between the -35 and -10 regions of the promoter or by deletion of porA. To reveal additional mechanisms of variation in PorA expression, the

  11. 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.

  12. 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

  13. 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

  14. 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.

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

    Science.gov (United States)

    Sjölinder, Hong; Jonsson, Ann-Beth

    2010-11-18

    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.

  16. Olfactory Nerve—A Novel Invasion Route of Neisseria meningitidis to Reach the Meninges

    Science.gov (United States)

    Sjölinder, Hong; Jonsson, Ann-Beth

    2010-01-01

    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. PMID:21124975

  17. 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.

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

    African Journals Online (AJOL)

    ADOWIE PERE

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

  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. 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 ...

  1. 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.

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

    Science.gov (United States)

    Rui, Lixin; Goodnow, Christopher C

    2006-05-01

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

  3. 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.

  4. Recruitment of a penicillin-binding protein gene from Neisseria flavescens during the emergence of penicillin resistance in Neisseria meningitidis

    OpenAIRE

    SPRATT, BG; ZHANG, QY; JONES, DM; HUTCHISON, A; BRANNIGAN, JA; DOWSON, CG

    1989-01-01

    Non-beta-lactamase-producing, penicillin-resistant strains of Neisseria meningitidis produce altered forms of penicillin-binding protein 2 that have decreased affinity for penicillin. The sequence of the penicillin-binding protein 2 gene (penA) from a penicillin-resistant strain of N. meningitidis was compared to the sequence of the same gene from penicillin-sensitive strains and from penicillin-sensitive and penicillin-resistant strains of Neisseria gonorrhoeae. The penA genes from penicilli...

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  6. 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

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

    Directory of Open Access Journals (Sweden)

    C. Parthasarathy

    2013-03-01

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

  8. Epigenetic control of CD8+ T cell differentiation.

    Science.gov (United States)

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

    2018-05-01

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

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

    Science.gov (United States)

    Hua, Yiding; Jiang, Haobin; Geng, Guoqing

    2017-03-01

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

  10. 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...

  11. 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.

  12. 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.

  13. Enhancement of recovery of Neisseria meningitidis by gelatin in blood culture media.

    OpenAIRE

    Pai, C H; Sorger, S

    1981-01-01

    The efficacy of gelatin for the recovery of Neisseria meningitidis from blood cultures was evaluated in a clinical setting. The organism was isolated from seven patients with meningococcal infections in blood culture media containing 1% gelatin. In contrast, only two blood cultures from these patients were positive in media without gelatin (P less than 0.05). Gelatin did not influence the recovery of other organisms isolated during this study. Conventional blood culture media may be supplemen...

  14. 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

  15. 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

  16. 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

  17. 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

  18. 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.

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

    Science.gov (United States)

    Aloni, Roni

    2013-11-01

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

  20. 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...

  1. 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

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

    NARCIS (Netherlands)

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

    2010-01-01

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

  3. Genetic control of differential acetylation in diabetic rats.

    Directory of Open Access Journals (Sweden)

    Pamela J Kaisaki

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

  4. 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.

  5. 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

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

    DEFF Research Database (Denmark)

    Krishnaswamy, Vijayaraghavan

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

  7. 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...

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

    International Nuclear Information System (INIS)

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

    2009-01-01

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

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

    Science.gov (United States)

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

    2016-12-01

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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2007-08-21

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

  12. 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.

  13. 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.

  14. 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.

  15. 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

  16. Encuesta de portadores de Neisseria meningitidis en el Área de Salud de Gran Canaria

    Directory of Open Access Journals (Sweden)

    García Rojas Amós

    2000-01-01

    Full Text Available FUNDAMENTOS: Se plantea A Conocer la tasa de portadores y los tipos circulantes de Neisseria Meningitidis en la población residente en el área de salud de Gran Canaria. B Conocer el patrón de distribución de estos portadores. MÉTODOS: Se realizó un diseño descriptivo transversal, con un muestreo aleatorio en etapas múltiples y por conglomerados. Se determinó un tamaño muestral mínimo de 707 personas para una prevalencia esperada del 8,6 %, con una confianza del 95,6 % y precisión de 0,02. Asumiendo que un 15 % de las personas no quisieran colaborar, se incrementó el tamaño muestral a 831 personas, distribuidas en cada conglomerado de manera proporcional a la población existente. Este tamaño se distribuyó a su vez, en cuatro grandes grupos de edad y sexo, proporcionalmente a su importancia en cada zona básica de salud seleccionada aleatoriamente. Los individuos de la muestra se identificaban entre los que acudían a las unidades de extracción, y una vez superados los criterios de exclusión se les solicitaba su colaboración voluntaria en el estudio. Si aceptaban, se les cumplimentaba un cuestionario que englobaba diferentes variables de interés epidemiológico y se les realizaba un frotis faríngeo. Al haber seleccionado los equipos de Atención Primaria con muestreo aleatorio simple y seguir el mismo método para elegir los individuos dentro de ellos, la estimación de la prevalencia se realizó mediante estimador no sesgado. RESULTADOS: Se obtuvieron un total de 828 muestras, lo que supuso un 99,6% de las previstas. Salvo tres, todos los individuos seleccionados participaron voluntariamente en el estudio, lo que le confiere una alta representatividad. Todas las cepas obtenidas correspondían a N. Meningitidis Serogrupo B, salvo una identificada como N. Meningitidis Serogrupo C Sero/Subtipo 4:P1.2,5. Las cepas de N. Meningitidis serogrupo B identificadas, correspondían a 25 serosubtipos diferentes. La prevalencia puntual

  17. 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

  18. Role of penA polymorphisms for penicillin susceptibility in Neisseria lactamica and Neisseria meningitidis.

    Science.gov (United States)

    Karch, André; Vogel, Ulrich; Claus, Heike

    2015-10-01

    In meningococci, reduced penicillin susceptibility is associated with five specific mutations in the transpeptidase region of penicillin binding protein 2 (PBP2). We showed that the same set of mutations was present in 64 of 123 Neisseria lactamica strains obtained from a carriage study (MIC range: 0.125-2.0mg/L). The PBP2 encoding penA alleles in these strains were genetically similar to those found in intermediate resistant meningococci suggesting frequent interspecies genetic exchange. Fifty-six N. lactamica isolates with mostly lower penicillin MICs (range: 0.064-0.38mg/L) exhibited only three of the five mutations. The corresponding penA alleles were unique to N. lactamica and formed a distinct genetic clade. PenA alleles with no mutations on the other hand were unique to meningococci. Under penicillin selective pressure, genetic transformation of N. lactamica penA alleles in meningococci was only possible for alleles encoding five mutations, but not for those encoding three mutations; the transfer resulted in MICs comparable to those of meningococci harboring penA alleles that encoded PBP2 with five mutations, but considerably lower than those of the corresponding N. lactamica donor strains. Due to a transformation barrier the complete N. lactamica penA could not be transformed into N. meningitidis. In summary, penicillin MICs in N. lactamica were associated with the number of mutations in the transpeptidase region of PBP2. Evidence for interspecific genetic transfer was only observed for penA alleles associated with higher MICs, suggesting that alleles encoding only three mutations in the transpeptidase region are biologically not effective in N. meningitidis. Factors other than PBP2 seem to be responsible for the high levels of penicillin resistance in N. lactamica. A reduction of penicillin susceptibility in N. meningitidis by horizontal gene transfer from N. lactamica is unlikely to happen. Copyright © 2015 Elsevier GmbH. All rights reserved.

  19. 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

  20. 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.

  1. A Neisseria meningitidis fbpABC mutant is incapable of using nonheme iron for growth.

    Science.gov (United States)

    Khun, H H; Kirby, S D; Lee, B C

    1998-05-01

    The neisserial fbpABC locus has been proposed to act as an iron-specific ABC transporter system. To confirm this assigned function, we constructed an fbpABC mutant in Neisseria meningitidis by insertional inactivation of fbpABC with a selectable antibiotic marker. The mutant was unable to use iron supplied from human transferrin, human lactoferrin, or iron chelates. However, the use of iron from heme and human hemoglobin was unimpaired. These results support the obligatory participation of fbpABC in neisserial periplasmic iron transport and do not indicate a role for this genetic locus in the heme iron pathway.

  2. fbpABC gene cluster in Neisseria meningitidis is transcribed as an operon.

    Science.gov (United States)

    Khun, H H; Deved, V; Wong, H; Lee, B C

    2000-12-01

    The neisserial fbpABC locus has been proposed to constitute a single transcriptional unit. To confirm this operonic arrangement, transcription assays using reverse transcriptase PCR amplification were conducted with Neisseria meningitidis. The presence of fbpAB and fbpBC transcripts obtained by priming cDNA synthesis with an fbpC-sequence-specific oligonucleotide indicates that fbpABC is organized as a single expression unit. The ratio of fbpA to fbpABC mRNA was approximately between 10- to 20-fold, as determined by real-time quantitative PCR.

  3. 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.

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

    Directory of Open Access Journals (Sweden)

    David E. Barroso

    Full Text Available 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.

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

    Science.gov (United States)

    Johnston, Amal J; Gruissem, Wilhelm

    2009-01-01

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

  6. 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.

  7. 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...

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

    DEFF Research Database (Denmark)

    Cortijo, Cedric; Gouzi, Mathieu; Tissir, Fadel

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Xing-Xing Mei

    2015-06-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  11. 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.

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

    Science.gov (United States)

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

    2013-03-01

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

  13. 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

  14. 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.

  15. 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.

  16. Improved production process for native outer membrane vesicle vaccine against Neisseria meningitidis.

    Directory of Open Access Journals (Sweden)

    Bas van de Waterbeemd

    Full Text Available An improved detergent-free process has been developed to produce vaccine based on native outer membrane vesicles (NOMV against Neisseria meningitidis serogroup B. Performance was evaluated with the NonaMen vaccine concept, which provides broad coverage based on nine distinct PorA antigens. Scalable aseptic equipment was implemented, replacing undesirable steps like ultracentrifugation, inactivation with phenol, and the use of preservatives. The resulting process is more consistent and gives a higher yield than published reference processes, enabling NOMV production at commercial scale. Product quality met preliminary specifications for 9 consecutive batches, and an ongoing study confirmed real-time stability up to 12 months after production. As the NOMV had low endotoxic activity and induced high bactericidal titres in mice, they are expected to be safe and effective in humans. The production process is not limited to NonaMen and may be applicable for other N. meningitidis serogroups and other gram-negative pathogens. The current results therefore facilitate the late-stage development and clinical evaluation of NOMV vaccines.

  17. 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

  18. 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.

  19. 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

  20. Deletion of porA by recombination between clusters of repetitive extragenic palindromic sequences in Neisseria meningitidis

    NARCIS (Netherlands)

    van der Ende, A.; Hopman, C. T.; Dankert, J.

    1999-01-01

    PorA is an important component in a vaccine against infection with Neisseria meningitidis. However, porA-negative meningococci were isolated from patients, thereby potentially limiting the role of PorA-mediated immunity. To analyze the mechanism by which the porA deletion occurred, the regions

  1. 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,

  2. 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

  3. 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

  4. 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

  5. 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.

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

    Science.gov (United States)

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

    2015-11-01

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

  7. 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.

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

    Science.gov (United States)

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

    2017-04-24

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

  9. 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 ...

  10. 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.

  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. 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.

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

    Science.gov (United States)

    Matsueda, Ross L.; Heimer, Karen

    1987-01-01

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

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

    Science.gov (United States)

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

    2007-01-01

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

  15. 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.

  16. 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....

  17. 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.

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

    Science.gov (United States)

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

    2010-01-01

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

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  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. 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.

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

    Science.gov (United States)

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

    2017-04-11

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

  6. Immunogenicity of recombinant class 1 protein from Neisseria meningitidis refolded into phospholipid vesicles and detergent.

    Science.gov (United States)

    Niebla, O; Alvarez, A; Martín, A; Rodríguez, A; Delgado, M; Falcón, V; Guillén, G

    2001-05-14

    The possibility of eliciting bactericidal antibodies against a recombinant class 1 protein (P1) from Neisseria meningitidis, joined to the first 45 amino acids of the neisserial LpdA protein (PM82), was examined. P1 was produced in Escherichia coli as intracellular inclusion bodies, from which it was purified and reconstituted by (a) inclusion into phospholipid vesicles and detergent and (b) refolding in 0.1% SDS. When Balb/c mice were immunised, high titres of subtype-specific bactericidal antibodies against P1 were obtained in both cases. These results suggest that in spite of being a denaturing agent, it is possible to use SDS to reconstitute the P1 protein in a conformation that exposes the immunodominat regions.

  7. 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

    formation, whereas biofilm formation of cc with low point prevalence (ST-8 cc and ST-11 cc) was eDNA-independent. For initial biofilm formation, a ST-32 cc type strain, but not a ST-11 type strain, utilized eDNA. The release of eDNA was mediated by lytic transglycosylase and cytoplasmic N......-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....... On the contrary, spreaders (ST-11 and ST-8 cc) are unable to use eDNA for biofilm formation and might compensate for poor colonization properties by high transmission rates....

  8. 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.

  9. Neisseria meningitidis expressing lgtB lipopolysaccharide targets DC-SIGN and modulates dendritic cell function.

    Science.gov (United States)

    Steeghs, Liana; van Vliet, Sandra J; Uronen-Hansson, Heli; van Mourik, Andries; Engering, Anneke; Sanchez-Hernandez, Martha; Klein, Nigel; Callard, Robin; van Putten, Jos P M; van der Ley, Peter; van Kooyk, Yvette; van de Winkel, Jan G J

    2006-02-01

    Neisseria meningitidis lipopolysaccharide (LPS) has been identified as a major determinant of dendritic cell (DC) function. Here we report that one of a series of meningococcal mutants with defined truncations in the lacto-N-neotetraose outer core of the LPS exhibited unique strong adhesion and internalization properties towards DC. These properties were mediated by interaction of the GlcNAc(beta1-3)-Gal(beta1-4)-Glc-R oligosaccharide outer core of lgtB LPS with the dendritic-cell-specific ICAM-3 grabbing non-integrin (DC-SIGN) lectin receptor. Activation of DC-SIGN with this novel oligosaccharide ligand skewed T-cell responses driven by DC towards T helper type 1 activity. Thus, the use of lgtB LPS may provide a powerful instrument to selectively induce the desired arm of the immune response and potentially increase vaccine efficacy.

  10. Intercontinental spread of a genetically distinctive complex of clones of Neisseria meningitidis causing epidemic disease.

    Science.gov (United States)

    Caugant, D A; Frøholm, L O; Bøvre, K; Holten, E; Frasch, C E; Mocca, L F; Zollinger, W D; Selander, R K

    1986-07-01

    Strains of Neisseria meningitidis responsible for an epidemic of meningococcal disease occurring in Norway since the mid-1970s and for recent increases in the incidence of disease in several other parts of Europe have been identified by multilocus enzyme electrophoresis as members of a distinctive group of 22 closely related clones (the ET-5 complex). Clones of this complex have also colonized South Africa, Chile, Cuba, and Florida, where they have been identified as the causative agents of recent outbreaks of meningococcal disease. There is strong circumstantial evidence that outbreaks of disease occurring in Miami in 1981 and 1982 were caused in large part by bacteria that reached Florida via human immigrants from Cuba.

  11. 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.

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

    KAUST Repository

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

    2014-01-01

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

  13. 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.

  14. 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.

  15. 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

  16. A virulence-associated filamentous bacteriophage of Neisseria meningitidis increases host-cell colonisation.

    Directory of Open Access Journals (Sweden)

    Emmanuelle Bille

    2017-07-01

    Full Text Available Neisseria meningitidis is a commensal of human nasopharynx. In some circumstances, this bacteria can invade the bloodstream and, after crossing the blood brain barrier, the meninges. A filamentous phage, designated MDAΦ for Meningococcal Disease Associated, has been associated with invasive disease. In this work we show that the prophage is not associated with a higher virulence during the bloodstream phase of the disease. However, looking at the interaction of N. meningitidis with epithelial cells, a step essential for colonization of the nasopharynx, we demonstrate that the presence of the prophage, via the production of viruses, increases colonization of encapsulated meningococci onto monolayers of epithelial cells. The analysis of the biomass covering the epithelial cells revealed that meningococci are bound to the apical surface of host cells by few layers of heavily piliated bacteria, whereas, in the upper layers, bacteria are non-piliated but surrounded by phage particles which (i form bundles of filaments, and/or (ii are in some places associated with bacteria. The latter are likely to correspond to growing bacteriophages during their extrusion through the outer membrane. These data suggest that, as the biomass increases, the loss of piliation in the upper layers of the biomass does not allow type IV pilus bacterial aggregation, but is compensated by a large production of phage particles that promote bacterial aggregation via the formation of bundles of phage filaments linked to the bacterial cell walls. We propose that MDAΦ by increasing bacterial colonization in the mucosa at the site-of-entry, increase the occurrence of diseases.

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

    International Nuclear Information System (INIS)

    Heydanek, D.

    1997-01-01

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

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

    Science.gov (United States)

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

    2008-10-01

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

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

    International Nuclear Information System (INIS)

    Buettner, T.W.

    1992-01-01

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

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

    International Nuclear Information System (INIS)

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

    2016-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Parisa Kakanj

    2013-07-01

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

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

    Science.gov (United States)

    2018-03-14

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

  4. 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.

  5. 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.

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

    DEFF Research Database (Denmark)

    Zorig, Abdelmalik; Barkat, Said; Belkheiri, Mohammed

    2017-01-01

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

  7. 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

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

    Science.gov (United States)

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

    2013-02-15

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

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

    Science.gov (United States)

    Li, Guang

    2017-01-01

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

  10. 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

  11. 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.

  12. 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.

  13. 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.

  14. 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

  15. Impact of the conjugate vaccine, MenAfriVac, on carriage of serogroup A Neisseria meningitidis and disease transmission

    OpenAIRE

    Kristiansen, Paul Arne

    2013-01-01

    Neisseria meningitidis (Nm), also referred to as meningococcus, is a human commensal colonising the oropharynx, transmittable by close contact between healthy people. The bacterium can act as an opportunistic pathogen and cause bacterial meningitis and septicaemia. Meningococci are classified into 12 serogroups based on the composition of their polysaccharide (Ps) capsule. Six of these serogroups, serogroups A, B, C, W, X and Y cause meningococcal disease worldwide. The populations most affec...

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

    International Nuclear Information System (INIS)

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

    2008-01-01

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

  17. 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.

  18. 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.

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

    KAUST Repository

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

    2011-01-01

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

  20. 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.

  1. 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.

  2. 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.

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

    Science.gov (United States)

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

    2012-01-01

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

  4. 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)

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

    Directory of Open Access Journals (Sweden)

    Amélie Avet-Rochex

    2014-09-01

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

  6. 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

  7. 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.

  8. 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

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

    Directory of Open Access Journals (Sweden)

    Banaja Mohanty

    2014-09-01

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

  10. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-10-01

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

  12. 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.

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

    Science.gov (United States)

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

    2018-03-01

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

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

    Science.gov (United States)

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

    2017-02-01

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

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

    Science.gov (United States)

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

    2015-02-01

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

  16. 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

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

    Directory of Open Access Journals (Sweden)

    Cedric Cortijo

    2012-12-01

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

  18. 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

  19. 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.

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    F. Ghomanjani

    2016-10-01

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

  3. 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.

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

    International Nuclear Information System (INIS)

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

    2003-01-01

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

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

    Science.gov (United States)

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

    2013-12-01

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

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

    Science.gov (United States)

    Rigatos, Gerasimos

    2016-12-01

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

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

    Science.gov (United States)

    2011-01-01

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

  8. 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.

  9. 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.

  10. Neisseria meningitidis antigen NMB0088: sequence variability, protein topology and vaccine potential.

    Science.gov (United States)

    Sardiñas, Gretel; Yero, Daniel; Climent, Yanet; Caballero, Evelin; Cobas, Karem; Niebla, Olivia

    2009-02-01

    The significance of Neisseria meningitidis serogroup B membrane proteins as vaccine candidates is continually growing. Here, we studied different aspects of antigen NMB0088, a protein that is abundant in outer-membrane vesicle preparations and is thought to be a surface protein. The gene encoding protein NMB0088 was sequenced in a panel of 34 different meningococcal strains with clinical and epidemiological relevance. After this analysis, four variants of NMB0088 were identified; the variability was confined to three specific segments, designated VR1, VR2 and VR3. Secondary structure predictions, refined with alignment analysis and homology modelling using FadL of Escherichia coli, revealed that almost all the variable regions were located in extracellular loop domains. In addition, the NMB0088 antigen was expressed in E. coli and a procedure for obtaining purified recombinant NMB0088 is described. The humoral immune response elicited in BALB/c mice was measured by ELISA and Western blotting, while the functional activity of these antibodies was determined in a serum bactericidal assay and an animal protection model. After immunization in mice, the recombinant protein was capable of inducing a protective response when it was administered inserted into liposomes. According to our results, the recombinant NMB0088 protein may represent a novel antigen for a vaccine against meningococcal disease. However, results from the variability study should be considered for designing a cross-protective formulation in future studies.

  11. Lipoprotein NMB0928 from Neisseria meningitidis serogroup B as a novel vaccine candidate.

    Science.gov (United States)

    Delgado, Maité; Yero, Daniel; Niebla, Olivia; González, Sonia; Climent, Yanet; Pérez, Yusleydis; Cobas, Karem; Caballero, Evelín; García, Darien; Pajón, Rolando

    2007-12-05

    Polysaccharide-based vaccines for serogroup B Neisseria meningitidis have failed to induce protective immunity. As a result, efforts to develop vaccines for serogroup B meningococcal disease have mostly focused on outer membrane proteins (OMP). Vaccine candidates based on meningococcal OMP have emerged in the form of outer membrane vesicles (OMVs) or, more recently, purified recombinant proteins, as alternative strategies for serogroup B vaccine development. In our group, the protein composition of the Cuban OMVs-based vaccine VA-MENGOC-BC was elucidated using two-dimensional gel electrophoresis and mass spectrometry. The proteomic map of this product allowed the identification of new putative protective proteins not previously reported as components of an antimeningococcal vaccine. In the present study, we have determined the immunogenicity and protective capacity of NMB0928, one of those proteins present in the OMVs. The antigen was obtained as a recombinant protein in Escherichia coli, purified and used to immunize mice. The antiserum produced against the protein was capable to recognize the natural protein in different meningococcal strains by whole-cell ELISA and Western blotting. After immunization, recombinant NMB0928 induced bactericidal antibodies, and when the protein was administered inserted into liposomes, the elicited antibodies were protective in the infant rat model. These results suggest that NMB0928 is a novel antigen worth to be included in a broadly protective meningococcal vaccine.

  12. 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.

  13. 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.

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

    Science.gov (United States)

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

    2017-07-01

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

  15. 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.

  16. 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.

  17. 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.

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

    Science.gov (United States)

    Mazandarani, Mehran; Pariz, Naser

    2018-05-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  20. 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

  1. Vigilancia de Neisseria meningitidis en Argentina, 1993-2005: distribución de serogrupos, serotipos y serosubtipos causantes de enfermedad invasiva

    OpenAIRE

    Chiavetta, L.; Chávez, E.; Ruzic, A.; Mollerach, M.; Regueira, M.

    2007-01-01

    Neisseria meningitidis es agente causal de enfermedades severas como meningitis, bacteriemia y síndrome de shock séptico. Se presenta la distribución en serogrupos, serotipos y serosubtipos de 2244 aislamientos de N. meningitidis obtenidos de cuadros de meningitis y/o meningococcemia durante el período 1993-2005 y analizados en el Laboratorio Nacional de Referencia del INEI-ANLIS "Dr. Carlos G. Malbrán". Estos aislamientos eran provenientes de 33 hospitales de todo el país, conformados en una...

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

    Science.gov (United States)

    Lee, DoKyung; Kim, Eun Jin; Kilgore, Paul E; Kim, Soon Ae; Takahashi, Hideyuki; Ohnishi, Makoto; Anh, Dang Duc; Dong, Bai Qing; Kim, Jung Soo; Tomono, Jun; Miyamoto, Shigehiko; Notomi, Tsugunori; Kim, Dong Wook; Seki, Mitsuko

    2015-01-01

    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.

  3. 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.

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

    Science.gov (United States)

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

    2018-04-17

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

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

    Science.gov (United States)

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

    1999-09-10

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

  6. 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.

  7. 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

  8. 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.

  9. 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.

  10. 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.

  11. Geotemporal analysis of Neisseria meningitidis clones in the United States: 2000-2005.

    Directory of Open Access Journals (Sweden)

    Ann E Wiringa

    Full Text Available The detection of meningococcal outbreaks relies on serogrouping and epidemiologic definitions. Advances in molecular epidemiology have improved the ability to distinguish unique Neisseria meningitidis strains, enabling the classification of isolates into clones. Around 98% of meningococcal cases in the United States are believed to be sporadic.Meningococcal isolates from 9 Active Bacterial Core surveillance sites throughout the United States from 2000 through 2005 were classified according to serogroup, multilocus sequence typing, and outer membrane protein (porA, porB, and fetA genotyping. Clones were defined as isolates that were indistinguishable according to this characterization. Case data were aggregated to the census tract level and all non-singleton clones were assessed for non-random spatial and temporal clustering using retrospective space-time analyses with a discrete Poisson probability model.Among 1,062 geocoded cases with available isolates, 438 unique clones were identified, 78 of which had ≥2 isolates. 702 cases were attributable to non-singleton clones, accounting for 66.0% of all geocoded cases. 32 statistically significant clusters comprised of 107 cases (10.1% of all geocoded cases were identified. Clusters had the following attributes: included 2 to 11 cases; 1 day to 33 months duration; radius of 0 to 61.7 km; and attack rate of 0.7 to 57.8 cases per 100,000 population. Serogroups represented among the clusters were: B (n = 12 clusters, 45 cases, C (n = 11 clusters, 27 cases, and Y (n = 9 clusters, 35 cases; 20 clusters (62.5% were caused by serogroups represented in meningococcal vaccines that are commercially available in the United States.Around 10% of meningococcal disease cases in the U.S. could be assigned to a geotemporal cluster. Molecular characterization of isolates, combined with geotemporal analysis, is a useful tool for understanding the spread of virulent meningococcal clones and patterns of

  12. 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

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    International Nuclear Information System (INIS)

    Amengonu, Yawo H; Kakad, Yogendra P

    2014-01-01

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

  16. 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

  17. 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…

  18. 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.

  19. 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.

  20. 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

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

    Directory of Open Access Journals (Sweden)

    Zhang Shu-Jun

    2010-03-01

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

  2. [Surveillance of Neisseria meningitidis in Argentina, 1993-2005: distribution of serogroups, serotypes and serosubtypes isolated from invasive disease].

    Science.gov (United States)

    Chiávetta, L; Chávez, E; Ruzic, A; Mollerach, M; Regueira, M

    2007-01-01

    Neisseria meningitidis is an important cause of meningitis, bacteremia and septic shock syndrome. We herein present the distribution of serogroups, serotypes and serosubtypes of 2244 isolates of N. meningitidis from patients with meningitis or meningococcemia, received within the period 1993-2005, in the National Reference Laboratory, INEI-ANLIS "Dr. Carlos G. Malbrán", from 33 Argentine hospitals that are included in a National Network devoted to for the study of bacterial meningitis. Between 1993-1995, serogroup B was prevalent (66%) whereas in the period from 1995-2001, serogroup C prevailed (65%). However, following but after that period, the prevalence of serogroup B was recovered. In the last 5 years of the studied period, the serogroups Y and W135 represented as a whole a 15.6% as a whole whereas up to the year 2000 during the first 6 years they accounted for it was of 4.7%. Higher diversity in the distribution of serotypes and serosubtypes was observed within serogroup B. The nonsubtypable isolates throughout the period of study represented the 52.8%, this high percentage demonstrates the limited capacity of the serotyping for the determination of meningococcal/meningococcus subtypes. of meningococco.

  3. 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.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Stuart P. Weisberg

    2014-02-01

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

  6. 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.

  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. 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.

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

    Science.gov (United States)

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

    2015-01-01

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

  10. 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.

  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. 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

  13. 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

  14. 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

  15. 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

  16. Behavioural, emotional, and post-traumatic stress problems in children and adolescents, long term after septic shock caused by Neisseria meningitidis

    NARCIS (Netherlands)

    Vermunt, L. C. A. C.; Buysse, C. M. P.; Joosten, K. F. M.; Hazelzet, J. A.; Verhulst, F. C.; Utens, E. M. W. J.

    2008-01-01

    To assess the occurrence of a wide range of behavioural, emotional, and post-traumatic stress problems in children and adolescents, long term after septic shock caused by Neisseria meningitidis (MSS). This study included 6- to 17-year-old patients who survived MSS and were admitted to the PICU of

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

    Science.gov (United States)

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

    2013-09-01

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

  18. 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.

  19. 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

  20. 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

  1. 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.

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

    Science.gov (United States)

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

    2016-10-01

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

  3. 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.

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

    Science.gov (United States)

    Davarian, F.

    1994-01-01

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

  5. 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.

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

    Science.gov (United States)

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

    1997-01-01

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

  7. Vigilancia de Neisseria meningitidis en Argentina, 1993-2005: distribución de serogrupos, serotipos y serosubtipos causantes de enfermedad invasiva Surveillance of Neisseria meningitidis in Argentina, 1993-2005: Distribution of serogroups, serotypes and serosubtypes isolated from invasive disease

    OpenAIRE

    L. Chiavetta; E. Chávez; A. Ruzic; M. Mollerach; M. Regueira

    2007-01-01

    Neisseria meningitidis es agente causal de enfermedades severas como meningitis, bacteriemia y síndrome de shock séptico. Se presenta la distribución en serogrupos, serotipos y serosubtipos de 2244 aislamientos de N. meningitidis obtenidos de cuadros de meningitis y/o meningococcemia durante el período 1993-2005 y analizados en el Laboratorio Nacional de Referencia del INEI-ANLIS "Dr. Carlos G. Malbrán". Estos aislamientos eran provenientes de 33 hospitales de todo el país, conformados en una...

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

    OpenAIRE

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2017-09-01

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

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

    Science.gov (United States)

    Skuse, Gary R; Lamkin-Kennard, Kathleen A

    2013-01-01

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

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

    Science.gov (United States)

    Bi, Ran; Liu, Peng

    2016-03-31

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

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

    Science.gov (United States)

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

    2015-02-01

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

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

    Science.gov (United States)

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

    2011-09-01

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

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

    Science.gov (United States)

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

    1994-01-01

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

  15. 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. 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...... antagonist (C5aRa) and a complement receptor 1 (CR1)-blocking antibody (3D9) were examined. Most bacteria (80%) immediately bound to erythrocytes. The binding gradually declined over time, with a parallel increase in phagocytosis. Complement inhibition with compstatin reduced erythrocyte binding...... and bacterial C3 opsonization. In contrast, the C5aRa efficiently reduced phagocytosis, but did not affect the binding of bacteria to erythrocytes. The anti-CR1 blocking mAb dose-dependently reduced bacterial binding to erythrocytes to nil, with subsequent increased phagocytosis and oxidative burst. LPS had...

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

    Science.gov (United States)

    2010-01-01

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

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

    OpenAIRE

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

    2015-01-01

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

  19. 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.

  20. 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.

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

    Science.gov (United States)

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

    2016-01-01

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

  2. 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.

  3. 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.

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

    Science.gov (United States)

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

    2015-01-01

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

  5. 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...

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

    DEFF Research Database (Denmark)

    Wu, Xunwei; Quondamatteo, Fabio; Lefever, Tine

    2006-01-01

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

  7. 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.

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

    Directory of Open Access Journals (Sweden)

    M. Mallika Arjunan

    2014-01-01

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

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

    Science.gov (United States)

    Jamison, J. W.

    1994-01-01

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

  10. 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

  11. 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.

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

    Science.gov (United States)

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

    2017-09-12

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

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

    Directory of Open Access Journals (Sweden)

    Tetsuo Yasugi

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

  14. 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

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

    Science.gov (United States)

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

    2012-12-18

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

  16. 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

  17. 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.

  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

    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

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

    Science.gov (United States)

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

    2007-12-01

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

  1. 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....

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

    Science.gov (United States)

    Peterson, Jeffrey J; Keenan, Kevin G

    2018-02-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-02-15

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

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

    OpenAIRE

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

    2015-01-01

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

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

    Science.gov (United States)

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

    2016-04-28

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

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

    Directory of Open Access Journals (Sweden)

    Jian Hao

    2017-12-01

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

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

    Science.gov (United States)

    Manonmani, N; Subbiah, V; Sivakumar, L

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    N. Manonmani

    2015-01-01

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

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

    Science.gov (United States)

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

    2017-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Rene Olivares-Navarrete

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-10-15

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

  13. 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.

  14. 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.

  15. Immunization and chemical conjugation of Bm95 obtained from Pichia pastoris enhances the immune response against vaccinal protein and Neisseria meningitidis capsular polysaccharide

    Directory of Open Access Journals (Sweden)

    Rodriguez-Valle M

    2014-03-01

    Full Text Available Manuel Rodriguez-Valle,1 Leonardo Canan-Hadden,2 Olivia Niebla2 1Animal Biotechnology Division, 2Analytical Division, Centre for Genetic Engineering and Biotechnology, Havana, Cuba Abstract: The ectoparasite Rhipicephalus (Boophilus microplus causes severe economic losses to the cattle industry in tropical and subtropical regions, and transmits endoparasites, such as Babesia bovis. The glycoprotein Bm95 is homologous to Bm86, a surface membrane protein of gut epithelial cells in R. microplus, and has been shown to efficiently control this ectoparasite in regions of the Americas. The immunostimulant properties of Bm86 have already been demonstrated after its coinjection with hepatitis B surface antigen (HBsAg and the infectious bovine rhinotracheitis virus. This study evaluated the carrier and immunostimulant properties of Bm95 using low immunogenic Neisseria meningitidis capsular C polysaccharide (Men CpS and HBsAg. We produced two polysaccharide-Bm95 conjugates by carbodiimide (MenCpSBm-c and reductive amination (MenCpSBm-ra methods. These conjugates were characterized and evaluated in mice. Antibody titers against Men CpS were significantly higher in mice immunized with MenCpSBm-ra (2,350±250, P<0.01 than in those immunized with MenCpSBm-c (250±75 or Men CpS (570±104. The study data indicate effective immunological memory after booster inoculation in mice immunized with MenCpSBm-ra. Additionally, significant humoral immunity against HBsAg was documented in mice coimmunized via the intranasal route with recombinant Bm95 (11,400±345 and HBsAg (128,000±250 compared with mice immunized only with HBsAg (400±40 or Bm95 (5,461±150, P<0.01. In conclusion, the immunostimulatory properties of recombinant Bm95 make it a useful element for developing safer conjugated vaccines against bacterial pathogens and for evaluation against ticks and tick-borne diseases in the context of a polyvalent veterinary vaccine. Keywords: glycoconjugate, Bm86

  16. 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

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

    Directory of Open Access Journals (Sweden)

    Kian-Hong Ng

    2009-11-01

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

  18. 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.

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

    Directory of Open Access Journals (Sweden)

    S. S. Askar

    2017-01-01

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

  20. Microprocessor Activity Controls Differential miRNA Biogenesis In Vivo

    Directory of Open Access Journals (Sweden)

    Thomas Conrad

    2014-10-01

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

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

    Science.gov (United States)

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

    2012-01-01

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

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

    Science.gov (United States)

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

    2015-12-24

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

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

    Science.gov (United States)

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

    2006-09-01

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

  4. 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.

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

    DEFF Research Database (Denmark)

    Eberl, L; Winson, MK; Sternberg, C

    1996-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Laura Micheli

    2017-07-01

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

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

    Science.gov (United States)

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

    2014-02-01

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

  8. 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…

  9. 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…

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

    Science.gov (United States)

    Xie, Ting

    2013-01-01

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

  11. 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.

  12. Short-term and long-term antibody response by mice after immunization against Neisseria meningitidis B or diphtheria toxoid

    Directory of Open Access Journals (Sweden)

    G.P. Silva

    2013-02-01

    Full Text Available Serogroup B Neisseria meningitidis (MenB is a major cause of invasive disease in early childhood worldwide. The only MenB vaccine available in Brazil was produced in Cuba and has shown unsatisfactory efficacy when used to immunize millions of children in Brazil. In the present study, we compared the specific functional antibody responses evoked by the Cuban MenB vaccine with a standard vaccine against diphtheria (DTP: diphtheria, tetanus, pertussis after primary immunization and boosting of mice. The peak of bactericidal and opsonic antibody titers to MenB and of neutralizing antibodies to diphtheria toxoid (DT was reached after triple immunization with the MenB vaccine or DTP vaccine, respectively. However, 4 months after immunization, protective DT antibody levels were present in all DTP-vaccinated mice but in only 20% of the mice immunized against MenB. After 6 months of primary immunization, about 70% of animals still had protective neutralizing DT antibodies, but none had significant bactericidal antibodies to MenB. The booster doses of DTP or MenB vaccines produced a significant antibody recall response, suggesting that both vaccines were able to generate and maintain memory B cells during the period studied (6 months post-triple immunization. Therefore, due to the short duration of serological memory induced by the MenB vaccine (VA-MENGOC-BC® vaccine, its use should be restricted to outbreaks of meningococcal disease.

  13. 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

  14. 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.

  15. 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

  16. 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.

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

    International Nuclear Information System (INIS)

    Brunovský, Pavol; Černý, Aleš; Winkler, Michael

    2013-01-01

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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

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

    Directory of Open Access Journals (Sweden)

    Esteban Chávez Conde

    2011-01-01

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

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

    Science.gov (United States)

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

    2015-09-01

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

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

    NARCIS (Netherlands)

    Núñez-Queija, R.; Tan, H.-P.

    2006-01-01

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

  5. 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.

  6. 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.

  7. 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 ...

  8. 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.

  9. 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

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

    CERN Document Server

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

    2015-01-01

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

  11. 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....

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

    Directory of Open Access Journals (Sweden)

    Benjamin L King

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

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

    Directory of Open Access Journals (Sweden)

    Osnat eHadad-Ophir

    2016-01-01

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

  14. 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

  15. 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

  16. 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.

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

    Science.gov (United States)

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

    2017-07-01

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

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

    International Nuclear Information System (INIS)

    Tanaka, Toshiyuki; Suzuki, Yoshiaki

    2014-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Rodney K Lyn

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

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

    Science.gov (United States)

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

    2017-08-22

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

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

    Science.gov (United States)

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

    2006-01-04

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

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

    Directory of Open Access Journals (Sweden)

    Michael eHeide

    2015-08-01

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

  3. 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.

  4. 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.

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

    Directory of Open Access Journals (Sweden)

    Patricia Vieira Tiago

    2011-06-01

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

  6. 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 ...

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

    Science.gov (United States)

    Macuga, Kristen L; Frey, Scott H

    2014-05-15

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

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

    Science.gov (United States)

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

    2013-01-01

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

  9. 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…

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

    NARCIS (Netherlands)

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

    2008-01-01

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

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

    Science.gov (United States)

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

    2005-01-01

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

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

    Science.gov (United States)

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

    2005-01-01

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

  13. 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.

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

    Science.gov (United States)

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

    2010-01-01

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

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

    Science.gov (United States)

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

    2016-01-11

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

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

    Directory of Open Access Journals (Sweden)

    Jin Chun

    2014-09-01

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

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

    Science.gov (United States)

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

    2018-05-01

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

  18. 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.

  19. 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...

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

    Science.gov (United States)

    de Paiva Lima, Carolina; da Silva E Silva, Daniel Almeida; Damasceno, Samara; Ribeiro, Andrea Frozino; Rocha, Cristiane S; Berenguer de Matos, Alexandre H; Correia, Diego; Boerngen-Lacerda, Roseli; Brunialti Godard, Ana Lúcia

    2017-09-01

    Alcohol use disorder (AUD) is a complex multifactorial disease with heritability of ∼50% and corresponds to the state in which the body triggers a reinforcement or reward compulsive behavior due to ethanol consumption, even when faced with negative consequences. Although several studies have shown the impact of high ethanol intake on the prefrontal cortex (PFC) gene expression, few have addressed the relationship between the patterns of gene expression underlying the compulsive behaviour associated with relapsing. In this study, we used a chronic three-bottle free-choice mouse model to investigate the PFC transcriptome in three different groups of mice drinkers: 'Light drinkers' (preference for water throughout the experiment); 'Heavy drinkers' (preference for ethanol with a non-compulsive intake), and 'Inflexible drinkers' (preference for ethanol with a compulsive drinking component). Our aim was to correlate the intake patterns observed in this model with gene expression changes in the PFC, a brain region critical for the development and maintenance of alcohol addiction. We found that the Camk2a gene showed a downregulated profile only in the Inflexible when compared to the Light drinkers group, the Camk2n1 and Pkp2 genes showed an upregulated profile only in the Inflexible drinkers when compared to the Control group, and the Gja1 gene showed an upregulated profile in the Light and Inflexible drinkers when compared to the Control group. These different transcription patterns have been associated to the presence of alcohol, in the Camk2n1 and Gja1 genes; to the amount of ethanol consumed, in the Camk2a gene; and to the loss of control in the alcohol consumption, in the Pkp2 gene. Here, we provide, for the first time, the potential involvement of the Pkp2 gene in the compulsivity and loss of control over the voluntary ethanol consumption.

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

    Directory of Open Access Journals (Sweden)

    Jackie Lau

    2018-01-01

    Full Text Available Objective: The cocaine- and amphetamine-regulated transcript (CART codes for a pivotal neuropeptide important in the control of appetite and energy homeostasis. However, limited understanding exists for the defined effector sites underlying CART function, as discrepant effects of central CART administration have been reported. Methods: By combining Cart-cre knock-in mice with a Cart adeno-associated viral vector designed using the flip-excision switch (AAV-FLEX technology, specific reintroduction or overexpression of CART selectively in CART neurons in the arcuate nucleus (Arc and lateral hypothalamic area (LHA, respectively, was achieved. The effects on energy homeostasis control were investigated. Results: Here we show that CART neuron-specific reintroduction of CART into the Arc and LHA leads to distinct effects on energy homeostasis control. Specifically, CART reintroduction into the Arc of otherwise CART-deficient Cartcre/cre mice markedly decreased fat mass and body weight, whereas CART reintroduction into the LHA caused significant fat mass gain and lean mass loss, but overall unaltered body weight. The reduced adiposity in ArcCART;Cartcre/cre mice was associated with an increase in both energy expenditure and physical activity, along with significantly decreased Npy mRNA levels in the Arc but with no change in food consumption. Distinctively, the elevated fat mass in LHACART;Cartcre/cre mice was accompanied by diminished insulin responsiveness and glucose tolerance, greater spontaneous food intake, and reduced energy expenditure, which is consistent with the observed decrease of brown adipose tissue temperature. This is also in line with significantly reduced tyrosine hydroxylase (Th and notably increased corticotropin-releasing hormone (Crh mRNA expressions in the paraventricular nucleus (PVN. Conclusions: Taken together, these results identify catabolic and anabolic effects of CART in the Arc and LHA, respectively, demonstrating for

  2. 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

  3. Differential effects of absent visual feedback control on gait variability during different locomotion speeds.

    Science.gov (United States)

    Wuehr, M; Schniepp, R; Pradhan, C; Ilmberger, J; Strupp, M; Brandt, T; Jahn, K

    2013-01-01

    Healthy persons exhibit relatively small temporal and spatial gait variability when walking unimpeded. In contrast, patients with a sensory deficit (e.g., polyneuropathy) show an increased gait variability that depends on speed and is associated with an increased fall risk. The purpose of this study was to investigate the role of vision in gait stabilization by determining the effects of withdrawing visual information (eyes closed) on gait variability at different locomotion speeds. Ten healthy subjects (32.2 ± 7.9 years, 5 women) walked on a treadmill for 5-min periods at their preferred walking speed and at 20, 40, 70, and 80 % of maximal walking speed during the conditions of walking with eyes open (EO) and with eyes closed (EC). The coefficient of variation (CV) and fractal dimension (α) of the fluctuations in stride time, stride length, and base width were computed and analyzed. Withdrawing visual information increased the base width CV for all walking velocities (p < 0.001). The effects of absent visual information on CV and α of stride time and stride length were most pronounced during slow locomotion (p < 0.001) and declined during fast walking speeds. The results indicate that visual feedback control is used to stabilize the medio-lateral (i.e., base width) gait parameters at all speed sections. In contrast, sensory feedback control in the fore-aft direction (i.e., stride time and stride length) depends on speed. Sensory feedback contributes most to fore-aft gait stabilization during slow locomotion, whereas passive biomechanical mechanisms and an automated central pattern generation appear to control fast locomotion.

  4. Rapid evolution leads to differential population dynamics and top-down control in resurrected Daphnia populations.

    Science.gov (United States)

    Goitom, Eyerusalem; Kilsdonk, Laurens J; Brans, Kristien; Jansen, Mieke; Lemmens, Pieter; De Meester, Luc

    2018-01-01

    There is growing evidence of rapid genetic adaptation of natural populations to environmental change, opening the perspective that evolutionary trait change may subsequently impact ecological processes such as population dynamics, community composition, and ecosystem functioning. To study such eco-evolutionary feedbacks in natural populations, however, requires samples across time. Here, we capitalize on a resurrection ecology study that documented rapid and adaptive evolution in a natural population of the water flea Daphnia magna in response to strong changes in predation pressure by fish, and carry out a follow-up mesocosm experiment to test whether the observed genetic changes influence population dynamics and top-down control of phytoplankton. We inoculated populations of the water flea D. magna derived from three time periods of the same natural population known to have genetically adapted to changes in predation pressure in replicate mesocosms and monitored both Daphnia population densities and phytoplankton biomass in the presence and absence of fish. Our results revealed differences in population dynamics and top-down control of algae between mesocosms harboring populations from the time period before, during, and after a peak in fish predation pressure caused by human fish stocking. The differences, however, deviated from our a priori expectations. An S-map approach on time series revealed that the interactions between adults and juveniles strongly impacted the dynamics of populations and their top-down control on algae in the mesocosms, and that the strength of these interactions was modulated by rapid evolution as it occurred in nature. Our study provides an example of an evolutionary response that fundamentally alters the processes structuring population dynamics and impacts ecosystem features.

  5. 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.

  6. 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

  7. Differential effects of mental stress on plasma homovanillic acid in schizophrenia and normal controls.

    Science.gov (United States)

    Sumiyoshi, T; Saitoh, O; Yotsutsuji, T; Itoh, H; Kurokawa, K; Kurachi, M

    1999-04-01

    We previously reported that mental stress by Kraepelin's arithmetic test decreases plasma homovanillic acid (pHVA) levels in psychiatrically normal healthy human subjects. The present study was undertaken to determine whether this pattern of changes in pHVA concentrations resulting from mental stress is altered in patients with schizophrenia. Fourteen male patients with schizophrenia including those under ongoing neuroleptic treatment and 14 normal male volunteers participated in the study. Following overnight fast and restricted physical activity, the subjects performed Kraepelin's arithmetic test for 30 minutes. Plasma samples were collected immediately before and after the test for measurement of pHVA levels. A significant diagnosis by Kraepelin's test effect was observed due to a decrease in pHVA levels by the Kraepelin test in control subjects but not in patients with schizophrenia. Changes in pHVA levels during the Kraepelin test positively correlated with pre-test pHVA levels in control subjects, while this correlation was not observed in patients with schizophrenia. These results may be further support for the presence of a dopamine-dependent restitutive system in the brain. The absence of response of pHVA levels to mental stress in patients with schizophrenia may indicate that the dopamine restitutive system in these patients is disrupted or already down-regulated, as previously predicted.

  8. 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.

  9. 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

  10. 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

  11. 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.

  12. eEF1A Controls ascospore differentiation through elevated accuracy, but controls longevity and fruiting body formation through another mechanism in Podospora anserina.

    Science.gov (United States)

    Silar, P; Lalucque, H; Haedens, V; Zickler, D; Picard, M

    2001-01-01

    Antisuppressor mutations in the eEF1A gene of Podospora anserina were previously shown to impair ascospore formation, to drastically increase life span, and to permit the development of the Crippled Growth degenerative process. Here, we show that eEF1A controls ascospore formation through accuracy level maintenance. Examination of antisuppressor mutant perithecia reveals two main cytological defects, mislocalization of spindle and nuclei and nuclear death. Antisuppression levels are shown to be highly dependent upon both the mutation site and the suppressor used, precluding any correlation between antisuppression efficiency and severity of the sporulation impairment. Nevertheless, severity of ascospore differentiation defect is correlated with resistance to paromomycin. We also show that eEF1A controls fruiting body formation and longevity through a mechanism(s) different from accuracy control. In vivo, GFP tagging of the protein in a way that partly retains its function confirmed earlier cytological observation; i.e., this factor is mainly diffuse within the cytosol, but may transiently accumulate within nuclei or in defined regions of the cytoplasm. These data emphasize the fact that the translation apparatus exerts a global regulatory control over cell physiology and that eEF1A is one of the key factors involved in this monitoring. PMID:11514440

  13. Differential effects of phenylephrine and norepinephrine on peripheral tissue oxygenation during general anaesthesia : A randomised controlled trial

    NARCIS (Netherlands)

    Poterman, Marieke; Vos, Jaap Jan; Vereecke, Hugo E. M.; Struys, Michel M. R. F.; Vanoverschelde, Henk; Scheeren, Thomas W. L.; Kalmar, Alain F.

    BACKGROUND Phenylephrine and norepinephrine are two vasopressors commonly used to counteract anaesthesia-induced hypotension. Their dissimilar working mechanisms may differentially affect the macro and microcirculation, and ultimately tissue oxygenation. OBJECTIVES We investigated the differential

  14. El ácido siálico N-acetilado es inmunogénico e induce anticuerpos protectores contra Neisseria meningitidis

    Directory of Open Access Journals (Sweden)

    Gregory R. Moe

    2009-08-01

    Full Text Available Recently, we showed that monoclonal antibodies (mAbs that are reactive with derivatives of polysialic acid containing de-N-acetylated neuraminic acid (Neu residues are protective against N. meningitidis group B strains (Moe et al. 2005, Infect Immun 73:2123; Flitter et al., in preparation. In addition, we found that fully de-N-acetylated PSA (i.e. poly alpha 2,8 Neu conjugated to tetanus toxoid (DeNAc elicits IgM and IgG antibodies of all subclasses in mice that bind to group B strains, activate human complement deposition, are protective in an infant rat model of meningococcal bacteremia and are bactericidal against group C strains (Moe et al, in press. We show here that anti-DeNAc mAbs, DA1 and DA2 (both IgM, are reactive with polysaccharides containing Neu, bind to group B, C, W135 and Y but not X strains grown in chemically defined media (CDM. However, when the group X strain is grown in CDM supplemented with human plasma, DA2 binds. Also both mAbs mediate bactericidal activity against B, C, W135, and X strains with human complement. The esults suggests that N. meningitidis express and/or acquire zwitterionic de-N-acetyl sialic acid antigens that can be the target of protective antibodies.

  15. Asymtomatic carriage of Neisseria meningitidis and Neisseria lactamica in relation to Streptococcus pneumoniae and Haemophilus influenzae colonization in healthy children: Apropos of 1400 children sampled

    International Nuclear Information System (INIS)

    Bakir, Mustafa; Yagci, Aysegul; Ulger, Nurver; Akbenlioglu, Cengiz; Ilki, Arzu; Soyletir, Guner

    2001-01-01

    Meningococcal disease is one of the most important causes of morbidity and mortality among children in many parts of the world. Main reservoir of carriage and site of meningococcal dissemination appears to be the upper respiratory tract. Colonization of Neisseria meningitidis and lactamica and factors affecting this carriage were determined in a group of healthy children aged 0-10 years. Meningococcus and N. lactamica carriage were detected in 17 (1.23%) and 245 (17.7%) of 1382 subjects, respectively. Number (%) of serogroups for meningococci was 1 (6), 5 (29), 0 (0), 1 (6), 1 (6), and 9 (53) for A, B, C, D, W135, and Y, respectively. Having more than three household members, elementary school attendance, pharyngeal carriage of Streptococcus pneumoniae and Haemophilus influenzae were associated with carriage of meningococci, whereas age less than 24-month was associated with carriage of N. lactamica. There was a reverse carriage rate between N. meningitidis and N. lactamica by age which may suggest a possible protective role of N. lactamica against meningococcal colonization among pre-school children

  16. Immunological evaluation in nonhuman primates of formulations based on the chimeric protein P64k-domain III of dengue 2 and two components of Neisseria meningitidis.

    Science.gov (United States)

    Valdés, Iris; Hermida, Lisset; Martín, Jorge; Menéndez, Tamara; Gil, Lázaro; Lazo, Laura; Castro, Jorge; Niebla, Olivia; López, Carlos; Bernardo, Lídice; Sánchez, Jorge; Romero, Yaremis; Martínez, Rafael; Guzmán, María G; Guillén, Gerardo

    2009-02-11

    The main problem in the development of successful vaccines against dengue based on recombinant proteins is the necessity to use potent adjuvants to reach a proper functional immune response. Our group reported the expression, characterization and immunological evaluation of the recombinant protein PD5, which contains the domain III of the Envelope protein from dengue 2 virus fused to the carrier protein P64k. This construct completely protected monkeys against viral challenge when the Freund's adjuvant was employed. Therefore, to define suitable formulations for human use, the present work relies on the evaluation of PD5, produced with a high purity and under GMP conditions, when formulated either with outer membrane vesicles (OMV) or the serogroup A capsular polysaccharide (CPS-A) from Neisseria meningitidis, both adsorbed on aluminium hydroxide. The antibody response to the formulation containing the CPS-A was clearly superior to that of the formulation with OMV. The experiment of in vivo protection supported this evidence, since only the group immunized with PD5 and CPS-A was partially protected upon viral challenge. This is the first study in which the polysaccharide A of N. meningitidis is successfully employed as adjuvant for viral antigens.

  17. Immunochemical studies and genetic background of two Neisseria meningitidis isolates expressing unusual capsule polysaccharide antigens with specificities of both serogroup Y and W135.

    Science.gov (United States)

    Tsang, Raymond S W; Tsai, Chao Ming; Henderson, Averil M; Tyler, Shaun; Law, Dennis K S; Zollinger, Wendell; Jamieson, Frances

    2008-03-01

    We described 2 unusual Neisseria meningitidis strains isolated from epidemiologically unrelated invasive meningococcal disease cases in Ontario, Canada. Both isolates have features typical of serogroup Y N. meningitidis: are of serotype 2c, are of the multi-locus sequence types typical of the serogroup Y strains in Canada, and are genotyped as serogroup Y based on a previously described PCR-ELISA method that detects the serogroup-Y-specific siaD gene. However, both strains were poly-agglutinable in both anti-Y and anti-W135 antisera. Further studies on 1 of these 2 isolates showed the presence of glucose and galactose as well as sialic acids in its purified capsular polysaccharide, suggesting the presence of both serogroup Y and serogroup W135 polysaccharides. Rabbit antisera produced to this strain contained antibodies to both purified serogroup Y and serogroup W135 capsular polysaccharides. Absorption experiments with either serogroup Y or serogroup W135 bacteria confirmed the presence of antibodies to these 2 different polysaccharides. DNA sequencing of the cps operon from both isolates revealed a siaD gene with 99.7% homology to the published siaD sequence from a serogroup Y strain but with 3 point mutations that all resulted in amino acid changes. How these strains may affect results of routine surveillance, PCR diagnosis, and immuno-protection by vaccination are discussed.

  18. Strong positive selection and recombination drive the antigenic variation of the PilE protein of the human pathogen Neisseria meningitidis.

    Science.gov (United States)

    Andrews, T Daniel; Gojobori, Takashi

    2004-01-01

    The PilE protein is the major component of the Neisseria meningitidis pilus, which is encoded by the pilE/pilS locus that includes an expressed gene and eight homologous silent fragments. The silent gene fragments have been shown to recombine through gene conversion with the expressed gene and thereby provide a means by which novel antigenic variants of the PilE protein can be generated. We have analyzed the evolutionary rate of the pilE gene using the nucleotide sequence of two complete pilE/pilS loci. The very high rate of evolution displayed by the PilE protein appears driven by both recombination and positive selection. Within the semivariable region of the pilE and pilS genes, recombination appears to occur within multiple small sequence blocks that lie between conserved sequence elements. Within the hypervariable region, positive selection was identified from comparison of the silent and expressed genes. The unusual gene conversion mechanism that operates at the pilE/pilS locus is a strategy employed by N. meningitidis to enhance mutation of certain regions of the PilE protein. The silent copies of the gene effectively allow "parallelized" evolution of pilE, thus enabling the encoded protein to rapidly explore a large area of sequence space in an effort to find novel antigenic variants.

  19. Aplicación de una biblioteca de anticuerpos lineales humanos frente al polisacárido capsular de Neisseria meningitidis serogrupo B

    Directory of Open Access Journals (Sweden)

    Emigdio León-Toirac

    2013-12-01

    Full Text Available Neisseria meningitidis serogrupo B produce aún morbimortalidad significativa. Su polisacárido capsular muestra similitud estructural con proteínas humanas y pobre inmunogenicidad, obstaculizando así el desarrollo de vacunas y anticuerpos monoclonales (AcM y policlonales contra esta bacteria. Recientemente se han creado bibliotecas artificiales de anticuerpos humanos expresados en bacteriófagos que reconocen específicamente a moléculas diana existentes, con la ventaja sobre los AcM convencionales por su rápida obtención, sin utilización de animales de laboratorio, lo que emerge como alternativa atractiva para la producción de AcM contra antígenos peculiares o complejos. Se realizó un trabajo de investigación básica, utilizando una biblioteca de fagos filamentosos que expresan constitutivamente regiones variables de anticuerpos humanos, que se enfrentó al polisacárido capsular de N. meningitidis serogrupo B. Los resultados que se obtuvieron mediante ELISA policlonal sugieren la existencia de anticuerpos humanos expresados en fagos que lo reconocen.

  20. Habituation and adaptation of the vestibuloocular reflex: a model of differential control by the vestibulocerebellum

    Science.gov (United States)

    Cohen, H.; Cohen, B.; Raphan, T.; Waespe, W.

    1992-01-01

    element that controls rapid changes in eye velocity in the VOR is separate from that which couples afferent input to velocity storage. Nodulouvulectomy caused a prompt and permanent loss of habituation, returning VOR time constants to initial values. VOR gain adaptation, which is lost after flocculectomy, was unaffected by nodulouvulectomy. Flocculectomy did not alter habituation of the VOR or of OKAN. Using a simplified model of the VOR, the decrease in the duration of vestibular nystagmus due to habituation was related to a decrement in the dominant time constant of the velocity storage integrator (1/h0).(ABSTRACT TRUNCATED AT 400 WORDS).

  1. Working mechanism of immunoglobulin A1 (IgA1) protease: cleavage of IgA1 antibody to Neisseria meningitidis PorA requires de novo synthesis of IgA1 Protease

    NARCIS (Netherlands)

    Vidarsson, Gestur; Overbeeke, Natasja; Stemerding, Annette M.; van den Dobbelsteen, Germie; van Ulsen, Peter; van der Ley, Peter; Kilian, Mogens; van de Winkel, Jan G. J.

    2005-01-01

    Neisseria meningitidis secretes a protease that specifically cleaves the hinge region of immunoglobulin A1 (IgA1), releasing the effector (Fc) domain of IgA1 from the antigen binding (Fab) determinants. Theoretically, the remaining Fab fragments can block pathogen receptors or toxins and still

  2. Working mechanism of immunoglobulin A1 (IgA1) protease: cleavage of IgA1 antibody to Neisseria meningitidis PorA requires de novo synthesis of IgA1 Protease

    DEFF Research Database (Denmark)

    Vidarsson, G; Overbeeke, N; Stemerding, AM

    2005-01-01

    Neisseria meningitidis secretes a protease that specifically cleaves the hinge region of immunoglobulin A1 (IgA1), releasing the effector (Fc) domain of IgA1 from the antigen binding (Fab) determinants. Theoretically, the remaining Fab fragments can block pathogen receptors or toxins and still...

  3. Neisseria meningitidis RTX protein FrpC induced high levels of serum antibodies during invasive disease: polymorphism of frpC alleles and purification of recombinant FrpC

    Czech Academy of Sciences Publication Activity Database

    Osička, Radim; Kalmusová, J.; Křížová, P.; Šebo, Peter

    2001-01-01

    Roč. 69, č. 9 (2001), s. 5509-5519 ISSN 0019-9567 R&D Projects: GA ČR GV310/96/K102; GA MŠk ME 167 Institutional research plan: CEZ:AV0Z5020903 Keywords : Neisseria meningitidis * meningococcal infections Subject RIV: EE - Microbiology, Virology Impact factor: 4.212, year: 2001

  4. Differential controls on soil carbon density and mineralization among contrasting forest types in a temperate forest ecosystem

    Science.gov (United States)

    You, Ye-Ming; Wang, Juan; Sun, Xiao-Lu; Tang, Zuo-Xin; Zhou, Zhi-Yong; Sun, Osbert Jianxin

    2016-01-01

    Understanding the controls on soil carbon dynamics is crucial for modeling responses of ecosystem carbon balance to global change, yet few studies provide explicit knowledge on the direct and indirect effects of forest stands on soil carbon via microbial processes. We investigated tree species, soil, and site factors in relation to soil carbon density and mineralization in a temperate forest of central China. We found that soil microbial biomass and community structure, extracellular enzyme activities, and most of the site factors studied varied significantly across contrasting forest types, and that the associations between activities of soil extracellular enzymes and microbial community structure appeared to be weak and inconsistent across forest types, implicating complex mechanisms in the microbial regulation of soil carbon metabolism in relation to tree species. Overall, variations in soil carbon density and mineralization are predominantly accounted for by shared effects of tree species, soil, microclimate, and microbial traits rather than the individual effects of the four categories of factors. Our findings point to differential controls on soil carbon density and mineralization among contrasting forest types and highlight the challenge to incorporate microbial processes for constraining soil carbon dynamics in global carbon cycle models. PMID:26925871

  5. 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.

  6. 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

  7. Safety and immunogenocity of a novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine in healthy Chinese children aged 6 months to 5 years old.

    Science.gov (United States)

    Hu, Jian-li; Tao, Hong; Li, Jing-xin; Dai, Wei-ming; Song, Bin; Sun, Jin-fang; Liu, Pei; Tang, Jie; Liu, Wen-yu; Wang, Shi-yuan; Zhu, Feng-cai

    2015-01-01

    A novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine (Hib-MenAC vaccine) has been developed to protect children against diseases caused by Hib, MenA, and MenC. This study investigated the safety and immunogenicity of the Hib-MenAC vaccine administered in 2-dose series to children aged 6-23 months and in a single dose to children aged 2-5 y. A randomized, positive-controlled, non-inferiority clinical trial was conducted for 1200 healthy participants in each age group. Within each age group, participants were randomly allocated to the Hib-MenAC group or the control group at a ratio of 1:1. Adverse reactions were recorded within 28 d after each dose. Blood samples were obtained to assess immunogenicity on day 0 and at 28 d after a complete vaccination course. For the investigational vaccine, the incidence of total adverse reactions in vaccinees aged 6-23 months was 46.8% and that in vaccinees aged 2-5 y was 29.8%. Most adverse reactions were mild or moderate. One non-fatal serious adverse event occurred in the Hib-MenAC group, but was unrelated to vaccination. The seroconversion rate to the 3 components reached 94.0%, and the proportion of vaccinees with rSBA titers ≥ 1:8 and PRP ≥ 0.15 g/mL reached 97.0% in both age groups. The safety and immunogenicity of the Hib-MenAC vaccine were non-inferior when compared to the licensed vaccines. It was concluded that the novel vaccine would be expected to protect children against all of the targeted diseases.

  8. 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

  9. Nitrogen consumption during batch cultivation of Neisseria meningitidis (serogroup C in Frantz medium Consumo de nitrogênio durante cultivo descontínuo de Neisseria meningitidis (sorogrupo C em meio de Frantz

    Directory of Open Access Journals (Sweden)

    Júlia Baruque-Ramos

    2001-12-01

    Full Text Available Capsular polysaccharide, extracted from microorganism cultivations, is the principal antigen for elaboration of vaccine against the disease caused by Neisseria meningitidis serogroup C. The final protein content allowed in this vaccine is 1%. In order to find a relationship between nitrogen consumption and cell growth, including polysaccharide production, and cell nitrogen content, cultivations were carried out in an 80 liters bioreactor (total capacity, under the following conditions: Frantz medium; temperature of 35ºC; air flow of 5 L/min (0.125 vvm; agitation frequency of 120 rpm and vessel pressure of 6 psi (kLa = 0.07 min-1. Concentrations of biomass, total polysaccharide, cellular nitrogen, residual organic and inorganic nitrogen in the medium were measured during cultivation. From five cultivations carried out under the same conditions, a mean cell nitrogen percentage of 12.6% (w/w in respect to the dry biomass was found. The inorganic nitrogen in the medium did not change significantly along the cultivation time, whereas the organic nitrogen consumption was linearly related to cell growth, with constant yield factors (average of 8.44. Polysaccharide production kinetics followed the cell growth kinetics until the beginning of the stationary growth phase. A supplemental polysaccharide production was observed until the end of cultivation, but without cell nitrogen absorption. Thus, the results indicate that polysaccharide is produced in two phases, being the first one biomass formation followed by non-associated to growth.Polissacarídeo capsular, extraído de cultivos microbianos, é o principal antígeno para o preparo da vacina contra a doença causada por Neisseria meningitidis sorogrupo C. O conteúdo final de proteína permitido nessa vacina é de 1%. De modo a encontrar uma relação entre o consumo de nitrogênio, o crescimento microbiano (incluindo a produção de polissacarídeo e o conteúdo de nitrogênio celular, cultivos

  10. Serogroup C Neisseria meningitidis invasive infection: analysis of the possible vaccination strategies for a mass campaign.

    Science.gov (United States)

    Chiappini, Elena; Venturini, Elisabetta; Bonsignori, Francesca; Galli, Luisa; de Martino, Maurizio

    2010-11-01

    The serogroup C meningococcal conjugate vaccine is available since 1999. In the absence of randomized controlled trials that support a specific schedule, each country has adopted different vaccination programmes. Hereby, we analyse positive and negative aspects of the different vaccination strategies. While waiting for the introduction of other antimeningococcal vaccines, covering also for the Group B meningococci, further studies on effectiveness of an optimal schedule to be adopted in European countries are needed. © 2010 The Author(s)/Journal Compilation © 2010 Foundation Acta Paediatrica.

  11. Optimal Control Method of Parabolic Partial Differential Equations and Its Application to Heat Transfer Model in Continuous Cast Secondary Cooling Zone

    Directory of Open Access Journals (Sweden)

    Yuan Wang

    2015-01-01

    Full Text Available Our work is devoted to a class of optimal control problems of parabolic partial differential equations. Because of the partial differential equations constraints, it is rather difficult to solve the optimization problem. The gradient of the cost function can be found by the adjoint problem approach. Based on the adjoint problem approach, the gradient of cost function is proved to be Lipschitz continuous. An improved conjugate method is applied to solve this optimization problem and this algorithm is proved to be convergent. This method is applied to set-point values in continuous cast secondary cooling zone. Based on the real data in a plant, the simulation experiments show that the method can ensure the steel billet quality. From these experiment results, it is concluded that the improved conjugate gradient algorithm is convergent and the method is effective in optimal control problem of partial differential equations.

  12. 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}.

  13. Differentiation of organic and non-organic winter wheat cultivars from a controlled field trial by crystallization patterns.

    Science.gov (United States)

    Kahl, Johannes; Busscher, Nicolaas; Mergardt, Gaby; Mäder, Paul; Torp, Torfinn; Ploeger, Angelika

    2015-01-01

    There is a need for authentication tools in order to verify the existing certification system. Recently, markers for analytical authentication of organic products were evaluated. Herein, crystallization with additives was described as an interesting fingerprint approach which needs further evidence, based on a standardized method and well-documented sample origin. The fingerprint of wheat cultivars from a controlled field trial is generated from structure analysis variables of crystal patterns. Method performance was tested on factors such as crystallization chamber, day of experiment and region of interest of the patterns. Two different organic treatments and two different treatments of the non-organic regime can be grouped together in each of three consecutive seasons. When the k-nearest-neighbor classification method was applied, approximately 84% of Runal samples and 95% of Titlis samples were classified correctly into organic and non-organic origin using cross-validation. Crystallization with additive offers an interesting complementary fingerprint method for organic wheat samples. When the method is applied to winter wheat from the DOK trial, organic and non-organic treated samples can be differentiated significantly based on pattern recognition. Therefore crystallization with additives seems to be a promising tool in organic wheat authentication. © 2014 Society of Chemical Industry.

  14. Mosquito control pesticides and sea surface temperatures have differential effects on the survival and oxidative stress response of coral larvae.

    Science.gov (United States)

    Ross, Cliff; Olsen, Kevin; Henry, Michael; Pierce, Richard

    2015-04-01

    The declining health of coral reefs is intensifying worldwide at an alarming rate due to the combined effects of land-based sources of pollution and climate change. Despite the persistent use of mosquito control pesticides in populated coastal areas, studies examining the survival and physiological impacts of early life-history stages of non-targeted marine organisms are limited. In order to better understand the combined effects of mosquito pesticides and rising sea surface temperatures, we exposed larvae from the coral Porites astreoides to selected concentrations of two major mosquito pesticide ingredients, naled and permethrin, and seawater elevated +3.5 °C. Following 18-20 h of exposure, larvae exposed to naled concentrations of 2.96 µg L(-1) or greater had significantly reduced survivorship compared to controls. These effects were not detected in the presence of permethrin or elevated temperature. Furthermore, larval settlement, post-settlement survival and zooxanthellae density were not impacted by any treatment. To evaluate the sub-lethal stress response of larvae, several oxidative stress endpoints were utilized. Biomarker responses to pesticide exposure were variable and contingent upon pesticide type as well as the specific biomarker being employed. In some cases, such as with protein carbonylation and catalase gene expression, the effects of naled exposure and temperature were interactive. In other cases pesticide exposure failed to induce any sub-lethal stress response. Overall, these results demonstrate that P. astreoides larvae have a moderate degree of resistance against short-term exposure to ecologically relevant concentrations of pesticides even in the presence of elevated temperature. In addition, this work highlights the importance of considering the complexity and differential responses encountered when examining the impacts of combined stressors that occur on varying spatial scales.

  15. 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.

  16. 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.

  17. 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.

  18. Critical analysis of old and new vaccines against N. meningitidis serogroup C, considering the meningococcal disease epidemiology in Brazil Análise crítica das antigas e novas vacinas contra a N. meningitidis do sorogrupo C, considerando a epidemiologia da doença meningocócica no Brasil

    Directory of Open Access Journals (Sweden)

    Lucia Ferro Bricks

    2003-01-01

    Full Text Available Worldwide, the impact of meningococcal disease is substantial, and the potential for the introduction and spread of more virulent strains of N. meningitidis or strains with increased resistance to current antibiotics causes concern, making prevention essential. OBJECTIVES: Review the indications for meningococcal disease vaccines, considering the epidemiological status in Brazil. METHODS: A critical literature review on this issue using the Medline and Lilacs databases. RESULTS: In Brazil, MenB and MenC were the most important serogroups identified in the 1990s. Polysaccharide vaccines available against those serogroups can offer only limited protection for infants, the group at highest risk for meningococcal disease. Additionally, polysaccharide vaccines may induce a hypo-responsive state to MenC. New meningococcal C conjugate vaccines could partially solve these problems, but it is unlikely that in the next few years a vaccine against MenB that can promote good protection against multiple strains of MenB responsible for endemic and epidemic diseases will become available. CONCLUSIONS: In order to make the best decision about recommendations on immunization practices, better quality surveillance data are required. In Brazil, MenC was responsible for about 2,000 cases per year during the last 10 years. New conjugate vaccines against MenC are very effective and immunogenic, and they should be recommended, especially for children less than 5 years old. Polysaccharide vaccines should be indicated only in epidemic situations and for high-risk groups. Until new vaccines against MenC and MenB are available for routine immunization programs, the most important measure for controlling meningococcal disease is early diagnosis of these infections in order to treat patients and to offer chemoprophylaxis to contacts.Em todo o mundo, o impacto das doenças meningocócicas é enorme e o potencial para a introdução e disseminação de cepas da N

  19. Portadores de Neisseria meningitidis, caracterización de las cepas aisladas y respuesta inmune basal a VA-MENGOC-BC

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    María J. Valdés

    2008-08-01

    Full Text Available 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 faríngeo y una extracción de sangre para la obtención de suero, así como una encuesta relacionada con aspectos de la investigación. La identificación de N. meningitidis se hizo por el sistema API NH (bioMérieux. Los serosubtipos e inmunotipos se clasificaron por ELISA de células enteras con anticuerpos monoclonales y la respuesta inmune basal se detectó por el Ensayo Bactericida del Suero. Se determinó la susceptibilidad antimicrobiana de las cepas frente a la penicilina, cloranfenicol, rifampicina, sulfadiacina sódica, ceftriaxona y ciprofloxacina. La prevalencia de portadores de N. meningitidis fue del 17%. Predominaron las cepas no agrupables (84,7%, seguidas por los serogrupos B (12,5% y Z (3,1%, destacándose la ausencia del C. Prevaleció el fenotipo NA:NT:P1.NST:L3,7,9 (12,5%, las cepas resistentes a la sulfadiacina (78,2% y sensibles a penicilina (81,3%, aunque el 18,7% mostró sensibilidad intermedia a este fármaco. Al resto de los antimicrobianos todas fueron sensibles. Se constató una respuesta inmune de memoria a la vacuna antimeningocócica (VAMENGOC-BC®, 12 años después de su aplicación, con títulos bactericidas anti C y B de 25 y 42%, respectivamente, resultados que pudieran estar influenciados por la inmunización sistemática que se realiza en Cuba con esta vacuna desde 1991.

  20. 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.

  1. 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

  2. Surveillance for Neisseria meningitidis Disease Activity and Transmission Using Information Technology.

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    S Sohail Ahmed

    Full Text Available While formal reporting, surveillance, and response structures remain essential to protecting public health, a new generation of freely accessible, online, and real-time informatics tools for disease tracking are expanding the ability to raise earlier public awareness of emerging disease threats. The rationale for this study is to test the hypothesis that the HealthMap informatics tools can complement epidemiological data captured by traditional surveillance monitoring systems for meningitis due to Neisseria meningitides (N. meningitides by highlighting severe transmissible disease activity and outbreaks in the United States.Annual analyses of N. meningitides disease alerts captured by HealthMap were compared to epidemiological data captured by the Centers for Disease Control's Active Bacterial Core surveillance (ABCs for N. meningitides. Morbidity and mortality case reports were measured annually from 2010 to 2013 (HealthMap and 2005 to 2012 (ABCs.HealthMap N. meningitides monitoring captured 80-90% of alerts as diagnosed N. meningitides, 5-20% of alerts as suspected cases, and 5-10% of alerts as related news articles. HealthMap disease alert activity for emerging disease threats related to N. meningitides were in agreement with patterns identified historically using traditional surveillance systems. HealthMap's strength lies in its ability to provide a cumulative "snapshot" of weak signals that allows for rapid dissemination of knowledge and earlier public awareness of potential outbreak status while formal testing and confirmation for specific serotypes is ongoing by public health authorities.The underreporting of disease cases in internet-based data streaming makes inadequate any comparison to epidemiological trends illustrated by the more comprehensive ABCs network published by the Centers for Disease Control. However, the expected delays in compiling confirmatory reports by traditional surveillance systems (at the time of writing, ABCs data

  3. A probable prehistoric case of meningococcal disease from San Francisco Bay: Next generation sequencing of Neisseria meningitidis from dental calculus and osteological evidence.

    Science.gov (United States)

    Eerkens, Jelmer W; Nichols, Ruth V; Murray, Gemma G R; Perez, Katherine; Murga, Engel; Kaijankoski, Phil; Rosenthal, Jeffrey S; Engbring, Laurel; Shapiro, Beth

    2018-05-25

    Next Generation Sequencing (NGS) of ancient dental calculus samples from a prehistoric site in San Francisco Bay, CA-SCL-919, reveals a wide range of potentially pathogenic bacteria. One older adult woman, in particular, had high levels of Neisseria meningitidis and low levels of Haemophilus influenzae, species that were not observed in the calculus from three other individuals. Combined with the presence of incipient endocranial lesions and pronounced meningeal grooves, we interpret this as an ancient case of meningococcal disease. This disease afflicts millions around the globe today, but little is known about its (pre)history. With additional sampling, we suggest NGS of calculus offers an exciting new window into the evolutionary history of these bacterial species and their interactions with humans. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Potential Capsule Switching from Serogroup Y to B: The Characterization of Three such Neisseria meningitidis Isolates Causing Invasive Meningococcal Disease in Canada

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    Raymond SW Tsang

    2005-01-01

    Full Text Available Three group B Neisseria meningitidis isolates, recovered from meningococcal disease cases in Canada and typed as B:2c:P1.5, were characterized. Multilocus sequence typing showed that all three isolates were related because of an identical sequence type (ST 573. Isolates typed as 2c:P1.5 are common in serogroup Y meningococci but rare in isolates from serogroups B or C. Although no serogroup Y isolates have been typed as ST-573, eight isolates showed five to six housekeeping gene alleles that were identical to that of ST-573. This suggested that the B:2c:P1.5 isolates may have originated from serogroup Y organisms, possibly by capsule switching.

  5. Carrier state of Haemophilus influenzae type b (Hib, Streptococcus pneumoniae, Streptococcus pyogenes, Neisseria meningitidis and Corynebacterium diphtheriae among school children in Pokhara, Nepal

    Directory of Open Access Journals (Sweden)

    Dharm Raj Bhatta

    2014-02-01

    Full Text Available Objective: To determine the incidence of carrier state of Haemophilus influenzae type b, Streptococcus pneumoniae (S. pneumoniae, Streptococcus pyogenes, Neisseria meningitidis and Corynebacterium diphtheriae among school children. Methods: Specimen from posterior pharyngeal wall and tonsils were collected on calcium alginate coated swabs from 1 02 participants. Processing of specimen and antimicrobial susceptibility testing was done by standard procedures. Results: Potential pathogens isolated in our study were S. pneumoniae (14.7%, Staphylococcus aureus (12.7%, Corynebacterium diphtheriae (3.9%, Streptococcus pyogenes (3.9% and Haemophilus influenzae (1.9%. Important findings in antibiogram include high resistance of S. pneumoniae to penicillin (73% and resistance of Staphylococcus aureus to oxacillin (23%. Conclusions: Pharyngeal colonization by S. pneumoniae among school children was found high and there is need of introduction of pneumococcal vaccines among children. Despite expected universal vaccination, pharyngeal colonization by Corynebacterium diphtheriae is possible and there is possibility of transmission.

  6. Differential benefits of amoxicillin-metronidazole in different phases of periodontal therapy in a randomized controlled crossover clinical trial.

    Science.gov (United States)

    Mombelli, Andrea; Almaghlouth, Adnan; Cionca, Norbert; Courvoisier, Delphine S; Giannopoulou, Catherine

    2015-03-01

    The specific advantage of administering systemic antibiotics during initial, non-surgical therapy or in the context of periodontal surgery is unclear. This study assesses the differential outcomes of periodontal therapy supplemented with amoxicillin-metronidazole during either the non-surgical or the surgical treatment phase. This is a single-center, randomized placebo-controlled crossover clinical trial with a 1-year follow-up. Eighty participants with Aggregatibacter actinomycetemcomitans-associated moderate to advanced periodontitis were randomized into two treatment groups: group A, antibiotics (500 mg metronidazole plus 375 mg amoxicillin three times per day for 7 days) during the first, non-surgical phase of periodontal therapy (T1) and placebo during the second, surgical phase (T2); and group B, placebo during T1 and antibiotics during T2. The number of sites with probing depth (PD) >4 mm and bleeding on probing (BOP) per patient was the primary outcome. A total of 11,212 sites were clinically monitored on 1,870 teeth. T1 with antibiotics decreased the number of sites with PD >4 mm and BOP per patient significantly more than without (group A: from 34.5 to 5.7, 84%; group B: from 28.7 to 8.7, 70%; P antibiotics, but only eight treated with placebo, achieved a 10-fold reduction of diseased sites (P = 0.007). Consequently, fewer patients of group A needed additional therapy, the mean number of surgical interventions was lower, and treatment time in T2 was shorter. Six months after T2, the mean number of residual pockets (group A: 2.8 ± 5.2; group B: 2.2 ± 5.0) was not significantly different and was sustained over 12 months in both groups. Giving the antibiotics during T1 or T2 yielded similar long-term outcomes, but antibiotics in T1 resolved the disease quicker and thus reduced the need for additional surgical intervention.

  7. Whole genome typing of the recently emerged Canadian serogroup W Neisseria meningitidis sequence type 11 clonal complex isolates associated with invasive meningococcal disease

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    Raymond S.W. Tsang

    2018-04-01

    Full Text Available Objectives: This study was performed to analyze the Canadian invasive serogroup W Neisseria meningitidis (MenW sequence type 11 (ST-11 clonal complex (CC isolates by whole genome typing and to compare Canadian isolates with similar isolates from elsewhere. Methods: Whole genome typing of 30 MenW ST-11 CC, 20 meningococcal group C (MenC ST-11 CC, and 31 MenW ST-22 CC isolates was performed on the Bacterial Isolate Genome Sequence database platform. Canadian MenW ST-11 CC isolates were compared with the 2000 MenW Hajj outbreak strain, as well as with MenW ST-11 CC from other countries. Results: Whole genome typing showed that the Canadian MenW ST-11 CC isolates were distinct from the traditional MenW ST-22 CC; they were not capsule-switched contemporary MenC strains that incorporated MenW capsules. While some recent MenW disease cases in Canada were caused by MenW ST-11 CC isolates showing relatedness to the 2000 MenW Hajj strain, many were non-Hajj isolates similar to current MenW ST-11 isolates found globally. Geographical and temporal variations in genotypes and surface protein antigen genes were found among the MenW ST-11 CC isolates. Conclusions: The current MenW ST-11 isolates did not arise by capsule switching from contemporary MenC ST-11 isolates. Both the Hajj-related and non-Hajj MenW ST-11 CC strains were associated with invasive meningococcal disease in Canada. Keywords: Neisseria meningitidis, Invasive meningococcal disease, Whole genome typing

  8. The Design of New Adjuvants for Mucosal Immunity to Neisseria meningitidis B in Nasally Primed Neonatal Mice for Adult Immune Response

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    Tatiane Ferreira

    2012-01-01

    Full Text Available The aim of this study was to determine the value of detoxified Shiga toxins Stx1 and Stx2 (toxoids of Escherichia coli as mucosal adjuvants in neonatal mice for immunogenicity against the outer membrane proteins (OMPs of Neisseria meningitidis B. Mucosal immunization has been shown to be effective for the induction of antigen-specific immune responses in both the systemic and mucosal compartments. Systemic antibody levels (IgG, IgG1, IgG2a, IgG2b, IgM, and IgA and mucosal IgM and IgA were measured by ELISA using an N. meningitidis as an antigen. In addition, IFN-γ and IL-6 production were measured after stimulated proliferation of immune cells. Intranasal administration elicited a higher anti-OMP IgA response in both saliva and vaginal fluids. Our results suggest that both Stx1 and Stx2 toxoids are effective mucosal adjuvants for the induction of Ag-specific IgG, IgM, and IgA antibodies. The toxoids significantly enhanced the IgG and IgM response against OMPs with a potency equivalent to CT, with the response being characterized by both IgG1 and IgG2a isotypes, and increased IFN-gamma production. Additionally, bactericidal activity was induced with IgG and IgM antibodies of high avidity. These results support the use of the new toxoids as potent inducing adjuvants that are particularly suitable for mucosal immunization.

  9. 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.

  10. 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.

  11. Dual-specificity phosphatase 10 controls brown adipocyte differentiation by modulating the phosphorylation of p38 mitogen-activated protein kinase.

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    Hye-Ryung Choi

    Full Text Available Brown adipocytes play an important role in regulating the balance of energy, and as such, there is a strong correlation between obesity and the amount of brown adipose tissue. Although the molecular mechanism underlying white adipocyte differentiation has been well characterized, brown adipocyte differentiation has not been studied extensively. Here, we investigate the potential role of dual-specificity phosphatase 10 (DUSP10 in brown adipocyte differentiation using primary brown preadipocytes.The expression of DUSP10 increased continuously after the brown adipocyte differentiation of mouse primary brown preadipocytes, whereas the phosphorylation of p38 was significantly upregulated at an early stage of differentiation followed by steep downregulation. The overexpression of DUSP10 induced a decrease in the level of p38 phosphorylation, resulting in lower lipid accumulation than that in cells overexpressing the inactive mutant DUSP10. The expression levels of several brown adipocyte markers such as PGC-1α, UCP1, and PRDM16 were also significantly reduced upon the ectopic expression of DUSP10. Furthermore, decreased mitochondrial DNA content was detected in cells expressing DUSP10. The results obtained upon treatment with the p38 inhibitor, SB203580, clearly indicated that the phosphorylation of p38 at an early stage is important in brown adipocyte differentiation. The effect of the p38 inhibitor was partially recovered by DUSP10 knockdown using RNAi.These results suggest that p38 phosphorylation is controlled by DUSP10 expression. Furthermore, p38 phosphorylation at an early stage is critical in brown adipocyte differentiation. Thus, the regulation of DUSP10 activity affects the efficiency of brown adipogenesis. Consequently, DUSP10 can be used as a novel target protein for the regulation of obesity.

  12. Caracterización de aislamientos invasivos de S. pneumoniae, H. influenzae y N. meningitidis en América Latina y el Caribe: SIREVA II, 2000-2005 Characterization of invasive isolates of S. pneumoniae, H. influenzae, and N. meningitidis in Latin America and the Caribbean: SIREVA II, 2000-2005

    Directory of Open Access Journals (Sweden)

    Jean-Marc Gabastou

    2008-07-01

    Full Text Available OBJETIVOS: Analizar las características fenotípicas y la susceptibilidad a antibióticos de las cepas circulantes de Streptococcus pneumoniae, Haemophilus influenzae y Neisseria meningitidis en América Latina y el Caribe entre 2000 y 2005. Se evaluó la cobertura potencial de las vacunas conjugadas. MÉTODOS: Se estudió por métodos convencionales la distribución de los serotipos o serogrupos de 17 303 cepas de S. pneumoniae, 2 782 cepas de H. influenzae y 6 955 cepas de N. meningitidis aisladas de casos de neumonía, meningitis, sepsis, bacteriemias y otros procesos invasivos. Se evaluó la susceptibilidad a los antibióticos de las cepas estudiadas. Los aislamientos procedían de 453 centros centinelas de 19 países de América Latina y 4 del Caribe, como parte del proyecto SIREVA II. RESULTADOS: El serotipo 14 de S. pneumoniae fue el más frecuentemente aislado (21,1%, especialmente en niños menores de 6 años (29,1%. Las coberturas potenciales de las vacunas conjugadas antineumocócicas hepta, nona, deca y tridecavalentes fueron de 59,0%, 73,4%, 76,5% y 85,9%, respectivamente. De los aislamientos, 63,3% eran sensibles a la penicilina. El serotipo b de H. influenzae estuvo presente en 72,2% de los aislamientos en niños menores de 2 años, mientras 8,6% correspondieron a los serotipos a, c, d, e y f; 19,2% resultaron no serotipables. La proporción de cepas de H. influenzae productoras de betalactamasa en aislamientos en niños menores de 2 años fue de 16,3%. Los serogrupos de N. meningitidis más frecuentes fueron el B (69,0% y el C (25,7%; 65,8% y 99,2% de las cepas fueron sensibles a la penicilina y a la rifampicina, respectivamente. CONCLUSIONES: Estos resultados resaltan la importancia de la vigilancia epidemiológica integral de S. pneumoniae, H. influenzae y N. meningitidis en América Latina y el Caribe. La gran heterogeneidad en la distribución de los serotipos de S. pneumoniae en los países estudiados podría reducir la

  13. Duplex recombinase polymerase amplification assays incorporating competitive internal controls for bacterial meningitis detection.

    Science.gov (United States)

    Higgins, Owen; Clancy, Eoin; Forrest, Matthew S; Piepenburg, Olaf; Cormican, Martin; Boo, Teck Wee; O'Sullivan, Nicola; McGuinness, Claire; Cafferty, Deirdre; Cunney, Robert; Smith, Terry J

    2018-04-01

    Recombinase polymerase amplification (RPA) is an isothermal nucleic acid amplification technology that provides rapid and robust infectious disease pathogen detection, ideal for point-of-care (POC) diagnostics in disease-prevalent low-resource countries. We have developed and evaluated three duplex RPA assays incorporating competitive internal controls for the detection of leading bacterial meningitis pathogens. Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae singleplex RPA assays were initially developed and evaluated, demonstrating 100% specificity with limits of detection of 4.1, 8.5 and 3.9 genome copies per reaction, respectively. Each assay was further developed into internally controlled duplex RPA assays via the incorporation of internal amplification control templates. Clinical performance of each internally controlled duplex RPA assay was evaluated by testing 64 archived PCR-positive clinical samples. Compared to real-time PCR, all duplex RPA assays demonstrated 100% diagnostic specificity, with diagnostic sensitivities of 100%, 86.3% and 100% for the S. pneumoniae, N. meningitidis and H. influenzae assays, respectively. This study details the first report of internally controlled duplex RPA assays for the detection of bacterial meningitis pathogens: S. pneumoniae, N. meningitidis and H. influenzae. We have successfully demonstrated the clinical diagnostic utility of each duplex RPA assay, introducing effective diagnostic technology for POC bacterial meningitis identification in disease-prevalent developing countries. Copyright © 2018 Elsevier Inc. All rights reserved.

  14. 14-3-3{sigma} controls corneal epithelial cell proliferation and differentiation through the Notch signaling pathway

    Energy Technology Data Exchange (ETDEWEB)

    Xin, Ying [Stem Cell Institute, James Brown Cancer Center, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202 (United States); Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202 (United States); Lu, Qingxian [Tumor Immunobiology Group, James Brown Cancer Center, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202 (United States); Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202 (United States); Department of Biochemistry and Molecular Biology, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202 (United States); Li, Qiutang, E-mail: q.li@louisville.edu [Stem Cell Institute, James Brown Cancer Center, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202 (United States); Department of Ophthalmology and Visual Sciences, University of Louisville School of Medicine, 301 E. Muhammad Ali Blvd., Louisville, KY 40202 (United States)

    2010-02-19

    14-3-3{sigma} (also called stratifin) is specifically expressed in the stratified squamous epithelium and its function was recently shown to be linked to epidermal stratification and differentiation in the skin. In this study, we investigated its role in corneal epithelium cell proliferation and differentiation. We showed that the 14-3-3{sigma} mutation in repeated epilation (Er) mutant mice results in a dominant negative truncated protein. Primary corneal epithelial cells expressing the dominant negative protein failed to undergo high calcium-induced cell cycle arrest and differentiation. We further demonstrated that blocking endogenous 14-3-3{sigma} activity in corneal epithelial cells by overexpressing dominative negative 14-3-3{sigma} led to reduced Notch activity and Notch1/2 transcription. Significantly, expression of the active Notch intracellular domain overcame the block in epithelial cell differentiation in 14-3-3{sigma} mutant-expressing corneal epithelial cells. We conclude that 14-3-3{sigma} is critical for regulating corneal epithelial proliferation and differentiation by regulating Notch signaling activity.

  15. 14-3-3σ controls corneal epithelial cell proliferation and differentiation through the Notch signaling pathway

    International Nuclear Information System (INIS)

    Xin, Ying; Lu, Qingxian; Li, Qiutang

    2010-01-01

    14-3-3σ (also called stratifin) is specifically expressed in the stratified squamous epithelium and its function was recently shown to be linked to epidermal stratification and differentiation in the skin. In this study, we investigated its role in corneal epithelium cell proliferation and differentiation. We showed that the 14-3-3σ mutation in repeated epilation (Er) mutant mice results in a dominant negative truncated protein. Primary corneal epithelial cells expressing the dominant negative protein failed to undergo high calcium-induced cell cycle arrest and differentiation. We further demonstrated that blocking endogenous 14-3-3σ activity in corneal epithelial cells by overexpressing dominative negative 14-3-3σ led to reduced Notch activity and Notch1/2 transcription. Significantly, expression of the active Notch intracellular domain overcame the block in epithelial cell differentiation in 14-3-3σ mutant-expressing corneal epithelial cells. We conclude that 14-3-3σ is critical for regulating corneal epithelial proliferation and differentiation by regulating Notch signaling activity.

  16. 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...

  17. Charge effects controlling the current hysteresis and negative differential resistance in periodical nanosize Si/CaF sub 2 structures

    CERN Document Server

    Berashevich, Y A; Kholod, A N; Borisenko, V E

    2002-01-01

    A kinetic model of charge carrier transport in nanosize periodical Si/CaF sub 2 structures via localized states in dielectric is proposed. Computer simulation of the current-voltage characteristics of such structures has shown that the built-in field arises in a dielectric due to polarization of the trapped charge by localized centers. This results in current hysteresis and negative differential resistance region at the current-voltage characteristics when the bias polarity is changed. At temperature below 250 K, the portion of negative differential resistance vanishes

  18. Recombinant Protein Truncation Strategy for Inducing Bactericidal Antibodies to the Macrophage Infectivity Potentiator Protein of Neisseria meningitidis and Circumventing Potential Cross-Reactivity with Human FK506-Binding Proteins

    OpenAIRE

    Bielecka, Magdalena K.; Devos, Nathalie; Gilbert, Mélanie; Hung, Miao-Chiu; Weynants, Vincent; Heckels, John E.; Christodoulides, Myron

    2014-01-01

    A recombinant macrophage infectivity potentiator (rMIP) protein of Neisseria meningitidis induces significant serum bactericidal antibody production in mice and is a candidate meningococcal vaccine antigen. However, bioinformatics analysis of MIP showed some amino acid sequence similarity to human FK506-binding proteins (FKBPs) in residues 166 to 252 located in the globular domain of the protein. To circumvent the potential concern over generating antibodies that could recognize human protein...

  19. Metabolismo intermedio e patogenicità microbica: studio della regolazione e dell’espressione differenziale del gene gdhA, codificante la L-glutammato deidrogenasi NADP-specifica, in isolati clinici di Neisseria meningitidis

    OpenAIRE

    Colicchio, Roberta

    2006-01-01

    Neisseria meningitidis (meningococco) è un batterio a ristretto spettro d’ospite e presenta “stili di vita” alternativi: commensale-patogeno, intracellulare-extracellulare. Un fattore cruciale per tale comportamento risiede nella capacità di sintetizzare ed utilizzare nutrienti essenziali per la propria sopravvivenza nei diversi microambienti dell’ospite durante un naturale ciclo infettivo. Dati di letteratura indicano che gdhA, codificante la L-glutammato deidrogenasi NADP-specifica (NADP...

  20. A cross-sectional study assessing the pharyngeal carriage of Neisseria meningitidis in subjects aged 1-24 years in the city of Embu das Artes, São Paulo, Brazil.

    Science.gov (United States)

    Weckx, Lily Yin; Puccini, Rosana Fiorini; Machado, Antónia; Gonçalves, Maria Gisele; Tuboi, Suely; de Barros, Eliana; Devadiga, Raghavendra; Ortega-Barria, Eduardo; Colindres, Romulo

    Meningococcal carriage is a prerequisite for invasive infection. This cross-sectional study assessed the pharyngeal carriage prevalence in healthy subjects aged 1-24 years in Embu das Artes city, São Paulo, Brazil. Pharyngeal swabs were examined for the presence of Neisseria meningitidis. The isolates were tested for different serogroups using agglutination and polymerase chain reaction. A logistic regression model assessed any independent association between Neisseria meningitidis carriage and various risk factors. A total of 87/967 subjects (9%, 95% Confidence Interval (CI): 7.3-11.0) tested positive for N. meningitidis: 6.2% (95% CI: 3.8-9.4) in 1-4 years, 8.5% (95% CI: 5.1-13.0) in 5-9 years, 12.5% (95% CI: 7.8-18.6) in 10-14 years, 12.6% (95% CI: 7.4-19.7) in 15-19 years and 9% (95% CI: 4.9-14.9) in 20-24 years age groups. Highest carriage prevalence was observed in adolescents 10-19 years old. Serogroup C was predominant (18.4%) followed by serogroup B (12.6%). The 15-19 years age group showed a significant association between number of household members and carriers of N. meningitidis. This cross-sectional study is the first in Brazil to evaluate meningococcal carriage prevalence and associated factors in a wide age range. Copyright © 2017 Sociedade Brasileira de Infectologia. Published by Elsevier Editora Ltda. All rights reserved.

  1. 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

  2. Pro-oxidant/antioxidant balance controls pancreatic β-cell differentiation through the ERK1/2 pathway.

    Science.gov (United States)

    Hoarau, E; Chandra, V; Rustin, P; Scharfmann, R; Duvillie, B

    2014-10-23

    During embryogenesis, the intrauterine milieu affects cell proliferation, differentiation, and function by modifying gene expression in susceptible cells, such as the pancreatic β-cells. In this limited energy environment, mitochondrial dysfunction can lead to overproduction of reactive oxygen species (ROS) and to a decline in β-cell function. In opposition to this toxicity, ROS are also required for insulin secretion. Here we investigated the role of ROS in β-cell development. Surprisingly, decreasing ROS production in vivo reduced β-cell differentiation. Moreover, in cultures of pancreatic explants, progenitors were highly sensitive to ROS stimulation and responded by generating β-cells. ROS enhanced β-cell differentiation through modulation of ERK1/2 signaling. Gene transfer and pharmacological manipulations, which diminish cellular ROS levels, also interfered with normal β-cell differentiation. This study highlights the role of the redox balance on β-cell development and provides information that will be useful for improving β-cell production from embryonic stem cells, a step in cell therapy for diabetes.

  3. 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

  4. IRF8 Transcription Factor Controls Survival and Function of Terminally Differentiated Conventional and Plasmacytoid Dendritic Cells, Respectively

    DEFF Research Database (Denmark)

    Sichien, Dorine; Scott, Charlotte L; Martens, Liesbet

    2016-01-01

    Interferon regulatory factor-8 (IRF8) has been proposed to be essential for development of monocytes, plasmacytoid dendritic cells (pDCs) and type 1 conventional dendritic cells (cDC1s) and remains highly expressed in differentiated DCs. Transcription factors that are required to maintain the ide...

  5. 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.

  6. The transcription factor Jdp2 controls bone homeostasis and antibacterial immunity by regulating osteoclast and neutrophil differentiation.

    Science.gov (United States)

    Maruyama, Kenta; Fukasaka, Masahiro; Vandenbon, Alexis; Saitoh, Tatsuya; Kawasaki, Takumi; Kondo, Takeshi; Yokoyama, Kazunari K; Kidoya, Hiroyasu; Takakura, Nobuyuki; Standley, Daron; Takeuchi, Osamu; Akira, Shizuo

    2012-12-14

    Jdp2 is an AP-1 family transcription factor that regulates the epigenetic status of histones. Previous in vitro studies revealed that Jdp2 is involved in osteoclastogenesis. However, the roles of Jdp2 in vivo and its pleiotropic functions are largely unknown. Here we generated Jdp2(-/-) mice and discovered its crucial roles not only in bone metabolism but also in differentiation of neutrophils. Jdp2(-/-) mice exhibited osteopetrosis resulting from impaired osteoclastogenesis. Jdp2(-/-) neutrophils were morphologically normal but had impaired surface expression of Ly6G, bactericidal function, and apoptosis. We also found that ATF3 was an inhibitor of neutrophil differentiation and that Jdp2 directly suppresses its expression via inhibition of histone acetylation. Strikingly, Jdp2(-/-) mice were highly susceptible to Staphylococcus aureus and Candida albicans infection. Thus, Jdp2 plays pivotal roles in in vivo bone homeostasis and host defense by regulating osteoclast and neutrophil differentiation. Copyright © 2012 Elsevier Inc. All rights reserved.

  7. Control of ductal vs. alveolar differentiation of mammary clonogens and susceptibility to radiation-induced mammary cancer

    International Nuclear Information System (INIS)

    Kamiya, Kenji; Yokoro, Kenjiro; Clifton, K.H.; Gould, M.N.

    1991-01-01

    We have developed an in vitro-in vivo transplantation assay for measuring the concentration of clonogenic epithelial cells in cell suspensions of rat mammary tissue. Rat mammary clonogens from organoid cultures are capable of the same degree of PLDR as clonogens in vivo. The growth and differentiation of mammary clonogens to alveolar colonies or ductal colonies is regulated as follows: a) in the presence of E 2 and high prolactin (Prl), cortisol induces mammary clonogens to proliferate and differentiate to form alveolar colonies which secrete milk and begin losing clonogenic potential, b) in cortisol deficient rats, Prl and E 2 synergistically stimulate non-secretory ductal colonies, formation of which retain clonogenic potential, c) E 2 without progesterone stimulates alveolar colony formation in the presence of cortical and high Prl, d) progesterone inhibits mammary clonogen differentiation to milk-producing cells and induces ductogenesis in a dose responsive fashion in the presence of E 2 , cortisol and high Prl. High prolactin levels coupled with glucocorticoid deficiency increases the susceptibility to mammary carcinogenesis following low dose radiation exposure by increasing the number of total mammary clonogens which are the presumptive target cells and by stimulating their proliferation after exposure. (author)

  8. Engineered Biomaterials Control Differentiation and Proliferation of Human-Embryonic-Stem-Cell-Derived Cardiomyocytes via Timed Notch Activation

    Directory of Open Access Journals (Sweden)

    Jason C. Tung

    2014-03-01

    Full Text Available For cell-based treatments of myocardial infarction, a better understanding of key developmental signaling pathways and more robust techniques for producing cardiomyocytes are required. Manipulation of Notch signaling has promise as it plays an important role during cardiovascular development, but previous studies presented conflicting results that Notch activation both positively and negatively regulates cardiogenesis. We developed surface- and microparticle-based Notch-signaling biomaterials that function in a time-specific activation-tunable manner, enabling precise investigation of Notch activation at specific developmental stages. Using our technologies, a biphasic effect of Notch activation on cardiac differentiation was found: early activation in undifferentiated human embryonic stem cells (hESCs promotes ectodermal differentiation, activation in specified cardiovascular progenitor cells increases cardiac differentiation. Signaling also induces cardiomyocyte proliferation, and repeated doses of Notch-signaling microparticles further enhance cardiomyocyte population size. These results highlight the diverse effects of Notch activation during cardiac development and provide approaches for generating large quantities of cardiomyocytes.

  9. Quasi-minimal active disturbance rejection control of MIMO perturbed linear systems based on differential neural networks and the attractive ellipsoid method.

    Science.gov (United States)

    Salgado, Iván; Mera-Hernández, Manuel; Chairez, Isaac

    2017-11-01

    This study addresses the problem of designing an output-based controller to stabilize multi-input multi-output (MIMO) systems in the presence of parametric disturbances as well as uncertainties in the state model and output noise measurements. The controller design includes a linear state transformation which separates uncertainties matched to the control input and the unmatched ones. A differential neural network (DNN) observer produces a nonlinear approximation of the matched perturbation and the unknown states simultaneously in the transformed coordinates. This study proposes the use of the Attractive Ellipsoid Method (AEM) to optimize the gains of the controller and the gain observer in the DNN structure. As a consequence, the obtained control input minimizes the convergence zone for the estimation error. Moreover, the control design uses the estimated disturbance provided by the DNN to obtain a better performance in the stabilization task in comparison with a quasi-minimal output feedback controller based on a Luenberger observer and a sliding mode controller. Numerical results pointed out the advantages obtained by the nonlinear control based on the DNN observer. The first example deals with the stabilization of an academic linear MIMO perturbed system and the second example stabilizes the trajectories of a DC-motor into a predefined operation point. Copyright © 2017 ISA. Published by Elsevier Ltd. All rights reserved.

  10. Differential gene expression in liver and small intestine from lactating rats compared to age-matched virgin controls detects increased mRNA of cholesterol biosynthetic genes

    Directory of Open Access Journals (Sweden)

    Jungsuwadee Paiboon

    2011-02-01

    Full Text Available Abstract Background Lactation increases energy demands four- to five-fold, leading to a two- to three-fold increase in food consumption, requiring a proportional adjustment in the ability of the lactating dam to absorb nutrients and to synthesize critical biomolecules, such as cholesterol, to meet the dietary needs of both the offspring and the dam. The size and hydrophobicity of the bile acid pool increases during lactation, implying an increased absorption and disposition of lipids, sterols, nutrients, and xenobiotics. In order to investigate changes at the transcriptomics level, we utilized an exon array and calculated expression levels to investigate changes in gene expression in the liver, duodenum, jejunum, and ileum of lactating dams when compared against age-matched virgin controls. Results A two-way mixed models ANOVA was applied to detect differentially expressed genes. Significance calls were defined as a p Cyp7a1, which catalyzes the rate limiting step in the bile acid biosynthetic pathway, was also significantly increased in liver. In addition, decreased levels of mRNA associated with T-cell signaling were found in the jejunum and ileum. Several members of the Solute Carrier (SLC and Adenosine Triphosphate Binding Cassette (ABC superfamilies of membrane transporters were found to be differentially expressed; these genes may play a role in differences in nutrient and xenobiotic absorption and disposition. mRNA expression of SLC39a4_predicted, a zinc transporter, was increased in all tissues, suggesting that it is involved in increased zinc uptake during lactation. Microarray data are available through GEO under GSE19175. Conclusions We detected differential expression of mRNA from several pathways in lactating dams, including upregulation of the cholesterol biosynthetic pathway in liver and intestine, consistent with Srebp activation. Differential T-Cell signaling in the two most distal regions of the small intestine (ileum and

  11. Vigilancia de Neisseria meningitidis en Argentina, 1993-2005: distribución de serogrupos, serotipos y serosubtipos causantes de enfermedad invasiva Surveillance of Neisseria meningitidis in Argentina, 1993-2005: Distribution of serogroups, serotypes and serosubtypes isolated from invasive disease

    Directory of Open Access Journals (Sweden)

    L. Chiavetta

    2007-03-01

    Full Text Available Neisseria meningitidis es agente causal de enfermedades severas como meningitis, bacteriemia y síndrome de shock séptico. Se presenta la distribución en serogrupos, serotipos y serosubtipos de 2244 aislamientos de N. meningitidis obtenidos de cuadros de meningitis y/o meningococcemia durante el período 1993-2005 y analizados en el Laboratorio Nacional de Referencia del INEI-ANLIS "Dr. Carlos G. Malbrán". Estos aislamientos eran provenientes de 33 hospitales de todo el país, conformados en una red nacional de laboratorios para el estudio de meningitis bacteriana. Durante el período 1993-1995 prevaleció el serogrupo B (66%, mientras que entre los años 1995 y 2001 prevaleció el serogrupo C (65%; a partir de esta fecha se restableció la prevalencia de B. En los últimos 5 años los serogrupos Y y W135 representaron en su conjunto el 15,6%, mientras que hasta el año 2000 no superaron el 4,7%. Se registró mayor diversidad en la distribución de serotipos y serosubtipos dentro del serogrupo B que dentro del serogrupo C. Los aislamientos no subtipables durante todo el período de estudio representaron el 52,8%; este elevado porcentaje evidencia la limitada capacidad de la serología para la determinación de subtipos de meningococo.Neisseria meningitidis is an important cause of meningitis, bacteremia and septic shock syndrome. We herein present the distribution of serogroups, serotypes and serosubtypes of 2244 isolates of N. meningitidis from patients with meningitis or meningococcemia, received within the period 1993-2005, in the National Reference Laboratory, INEI-ANLIS "Dr. Carlos G. Malbrán", from 33 Argentine hospitals that are included in a National Network devoted to for the study of bacterial meningitis. Between 1993-1995, serogroup B was prevalent (66% whereas in the period from 1995-2001, serogroup C prevailed (65%. However, following but after that period, the prevalence of serogroup B was recovered. In the last 5 years of the

  12. Bistability and hysteresis of the 'Secteur' differentiation are controlled by a two-gene locus in Nectria haematococca

    Directory of Open Access Journals (Sweden)

    Daboussi Marie-Josée

    2004-08-01

    Full Text Available Abstract Background Bistability and hysteresis are increasingly recognized as major properties of regulatory networks governing numerous biological phenomena, such as differentiation and cell cycle progression. The full scope of the underlying molecular mechanisms leading to bistability and hysteresis remains elusive. Nectria haemaotcocca, a saprophytic or pathogenic fungus with sexual reproduction, exhibits a bistable morphological modification characterized by a reduced growth rate and an intense pigmentation. Bistability is triggered by the presence or absence of σ, a cytoplasmic determinant. This determinant spreads in an infectious manner in the hyphae of the growing margin, insuring hysteresis of the differentiation. Results Seven mutants specifically affected in the generation of σ were selected through two different screening strategies. The s1 and s2 mutations completely abolish the generation of σ and of its morphological expression, the Secteur. The remaining five mutations promote its constitutive generation, which determines an intense pigmentation but not growth alteration. The seven mutations map at the same locus, Ses (for 'Secteur-specific'. The s2 mutant was obtained by an insertional mutagenesis strategy, which permitted the cloning of the Ses locus. Sequence and transcription analysis reveals that Ses is composed of two closely linked genes, SesA, mutated in the s1 and s2 mutant strains, and SesB, mutated in the s* mutant strains. SesB shares sequence similarity with animal and fungal putative proteins, with potential esterase/lipase/thioesterase activity, whereas SesA is similar to proteins of unknown function present only in the filamentous fungi Fusarium graminearum and Podospora anserina. Conclusions The cloning of Ses provides evidence that a system encoded by two linked genes directs a bistable and hysteretic switch in a eukaryote. Atypical regulatory relations between the two proteins may account for the hysteresis

  13. Bistability and hysteresis of the 'Secteur' differentiation are controlled by a two-gene locus in Nectria haematococca

    Science.gov (United States)

    Graziani, Stéphane; Silar, Philippe; Daboussi, Marie-Josée

    2004-01-01

    Background Bistability and hysteresis are increasingly recognized as major properties of regulatory networks governing numerous biological phenomena, such as differentiation and cell cycle progression. The full scope of the underlying molecular mechanisms leading to bistability and hysteresis remains elusive. Nectria haemaotcocca, a saprophytic or pathogenic fungus with sexual reproduction, exhibits a bistable morphological modification characterized by a reduced growth rate and an intense pigmentation. Bistability is triggered by the presence or absence of σ, a cytoplasmic determinant. This determinant spreads in an infectious manner in the hyphae of the growing margin, insuring hysteresis of the differentiation. Results Seven mutants specifically affected in the generation of σ were selected through two different screening strategies. The s1 and s2 mutations completely abolish the generation of σ and of its morphological expression, the Secteur. The remaining five mutations promote its constitutive generation, which determines an intense pigmentation but not growth alteration. The seven mutations map at the same locus, Ses (for 'Secteur-specific'). The s2 mutant was obtained by an insertional mutagenesis strategy, which permitted the cloning of the Ses locus. Sequence and transcription analysis reveals that Ses is composed of two closely linked genes, SesA, mutated in the s1 and s2 mutant strains, and SesB, mutated in the s* mutant strains. SesB shares sequence similarity with animal and fungal putative proteins, with potential esterase/lipase/thioesterase activity, whereas SesA is similar to proteins of unknown function present only in the filamentous fungi Fusarium graminearum and Podospora anserina. Conclusions The cloning of Ses provides evidence that a system encoded by two linked genes directs a bistable and hysteretic switch in a eukaryote. Atypical regulatory relations between the two proteins may account for the hysteresis of Secteur differentiation

  14. The nuclear hormone receptor family member NR5A2 controls aspects of multipotent progenitor cell formation and acinar differentiation during pancreatic organogenesis.

    Science.gov (United States)

    Hale, Michael A; Swift, Galvin H; Hoang, Chinh Q; Deering, Tye G; Masui, Toshi; Lee, Youn-Kyoung; Xue, Jumin; MacDonald, Raymond J

    2014-08-01

    The orphan nuclear receptor NR5A2 is necessary for the stem-like properties of the epiblast of the pre-gastrulation embryo and for cellular and physiological homeostasis of endoderm-derived organs postnatally. Using conditional gene inactivation, we show that Nr5a2 also plays crucial regulatory roles during organogenesis. During the formation of the pancreas, Nr5a2 is necessary for the expansion of the nascent pancreatic epithelium, for the subsequent formation of the multipotent progenitor cell (MPC) population that gives rise to pre-acinar cells and bipotent cells with ductal and islet endocrine potential, and for the formation and differentiation of acinar cells. At birth, the NR5A2-deficient pancreas has defects in all three epithelial tissues: a partial loss of endocrine cells, a disrupted ductal tree and a >90% deficit of acini. The acinar defects are due to a combination of fewer MPCs, deficient allocation of those MPCs to pre-acinar fate, disruption of acinar morphogenesis and incomplete acinar cell differentiation. NR5A2 controls these developmental processes directly as well as through regulatory interactions with other pancreatic transcriptional regulators, including PTF1A, MYC, GATA4, FOXA2, RBPJL and MIST1 (BHLHA15). In particular, Nr5a2 and Ptf1a establish mutually reinforcing regulatory interactions and collaborate to control developmentally regulated pancreatic genes by binding to shared transcriptional regulatory regions. At the final stage of acinar cell development, the absence of NR5A2 affects the expression of Ptf1a and its acinar specific partner Rbpjl, so that the few acinar cells that form do not complete differentiation. Nr5a2 controls several temporally distinct stages of pancreatic development that involve regulatory mechanisms relevant to pancreatic oncogenesis and the maintenance of the exocrine phenotype. © 2014. Published by The Company of Biologists Ltd.

  15. Targeting CD28, CTLA-4 and PD-L1 costimulation differentially controls immune synapses and function of human regulatory and conventional T-cells.

    Directory of Open Access Journals (Sweden)

    Nahzli Dilek

    Full Text Available CD28, CTLA-4 and PD-L1, the three identified ligands for CD80/86, are pivotal positive and negative costimulatory molecules that, among other functions, control T cell motility and formation of immune synapse between T cells and antigen-presenting cells (APCs. What remains incompletely understood is how CD28 leads to the activation of effector T cells (Teff but inhibition of suppression by regulatory T cells (Tregs, while CTLA-4 and PD-L1 inhibit Teff function but are crucial for the suppressive function of Tregs. Using alloreactive human T cells and blocking antibodies, we show here by live cell dynamic microscopy that CD28, CTLA-4, and PD-L1 differentially control velocity, motility and immune synapse formation in activated Teff versus Tregs. Selectively antagonizing CD28 costimulation increased Treg dwell time with APCs and induced calcium mobilization which translated in increased Treg suppressive activity, in contrast with the dampening effect on Teff responses. The increase in Treg suppressive activity after CD28 blockade was also confirmed with polyclonal Tregs. Whereas CTLA-4 played a critical role in Teff by reversing TCR-induced STOP signals, it failed to affect motility in Tregs but was essential for formation of the Treg immune synapse. Furthermore, we identified a novel role for PD-L1-CD80 interactions in suppressing motility specifically in Tregs. Thus, our findings reveal that the three identified ligands of CD80/86, CD28, CTLA-4 and PD-L1, differentially control immune synapse formation and function of the human Teff and Treg cells analyzed here. Individually targeting CD28, CTLA-4 and PD-L1 might therefore represent a valuable therapeutic strategy to treat immune disorders where effector and regulatory T cell functions need to be differentially targeted.

  16. Study on Differential Regenerative Braking Torque Control to Increase the Stability of the Small Electric Vehicle with Four In-Wheel Motors

    Directory of Open Access Journals (Sweden)

    Ali N. M.

    2017-01-01

    Full Text Available Based on the advantages of the electric motor such as fast and precise torque response, the performance of the electric vehicle (EV can be improved. During braking or driving on the cornering, the vehicle will over steer or under steer if a car turns by more or less than the amount commanded by the driver. To improve the stability of the small EV with four in-wheel motors, the differential regenerative braking torque control is proposed. In this system, the regenerative braking torque at each wheel will be controlled individually based on the value of slip ratio. If the slip ratio is greater than the optimum value, the regenerative brake will turn off. In this situation, the electric motor will not produce the regenerative braking torque. Conversely, if the slip ratio lower than the optimum value, the regenerative brake will turn on and the electric motor will generate the regenerative braking torque. In the numerical analysis, to investigate the effectiveness of the proposed model, the road condition is set to an icy road on the left tire and dry asphalt on the right tire. From the simulation results, the differential regenerative braking torque control can prevent the tire from lock-up and avoid the vehicle from skidding.

  17. MAPK pathway control of stem cell proliferation and differentiation in the embryonic pituitary provides insights into the pathogenesis of papillary craniopharyngioma.

    Science.gov (United States)

    Haston, Scott; Pozzi, Sara; Carreno, Gabriela; Manshaei, Saba; Panousopoulos, Leonidas; Gonzalez-Meljem, Jose Mario; Apps, John R; Virasami, Alex; Thavaraj, Selvam; Gutteridge, Alice; Forshew, Tim; Marais, Richard; Brandner, Sebastian; Jacques, Thomas S; Andoniadou, Cynthia L; Martinez-Barbera, Juan Pedro

    2017-06-15

    Despite the importance of the RAS-RAF-MAPK pathway in normal physiology and disease of numerous organs, its role during pituitary development and tumourigenesis remains largely unknown. Here, we show that the over-activation of the MAPK pathway, through conditional expression of the gain-of-function alleles BrafV600E and KrasG12D in the developing mouse pituitary, results in severe hyperplasia and abnormal morphogenesis of the gland by the end of gestation. Cell-lineage commitment and terminal differentiation are disrupted, leading to a significant reduction in numbers of most of the hormone-producing cells before birth, with the exception of corticotrophs. Of note, Sox2 + stem cells and clonogenic potential are drastically increased in the mutant pituitaries. Finally, we reveal that papillary craniopharyngioma (PCP), a benign human pituitary tumour harbouring BRAF p.V600E also contains Sox2 + cells with sustained proliferative capacity and disrupted pituitary differentiation. Together, our data demonstrate a crucial function of the MAPK pathway in controlling the balance between proliferation and differentiation of Sox2 + cells and suggest that persistent proliferative capacity of Sox2 + cells may underlie the pathogenesis of PCP. © 2017. Published by The Company of Biologists Ltd.

  18. Differential effect of exposure-based therapy and cognitive therapy on post-traumatic stress disorder symptom clusters: A randomized controlled trial.

    Science.gov (United States)

    Horesh, Danny; Qian, Meng; Freedman, Sara; Shalev, Arieh

    2017-06-01

    A question remains regarding differential effects of exposure-based versus non-exposure-based therapies on specific post-traumatic stress disorder (PTSD) symptom clusters. Traumatized emergency room patients were randomized to receive prolonged exposure (PE) or cognitive therapy (CT) without exposure. PE/CT had no differential effect on individual symptom clusters, and change in total PTSD score remained significant even after controlling for the reductions in all three symptom clusters. In addition, baseline levels of PTSD avoidance/intrusion/hyperarousal did not moderate the effects of PE and CT on total PTSD symptom scores. Taken together, these findings challenge the notion that PE and CT are specifically, and differentially, useful in treating one particular PTSD symptom cluster. Despite their different theoretical backgrounds and techniques, the notion that PE and CT (without exposure) target different PTSD symptoms was not confirmed in this study. Thus, both interventions may in fact be equally effective for treating intrusion, avoidance and hyperarousal symptoms. Baseline levels of avoidance, intrusion and hyperarousal may not be good a priori indicators for PTSD treatment selection. The effect of PE and CT on PTSD as a whole does not seem to depend on a reduction in any specific symptom cluster. These findings indicate that exposure and non-exposure interventions may lead to similar results in terms of reductions in specific PTSD symptoms. It is quite possible that individual PTSD clusters may respond to therapy in an inter-related fashion, with one cluster affecting the other. © 2016 The British Psychological Society.

  19. Ion torrent personal genome machine sequencing for genomic typing of Neisseria meningitidis for rapid determination of multiple layers of typing information.

    Science.gov (United States)

    Vogel, Ulrich; Szczepanowski, Rafael; Claus, Heike; Jünemann, Sebastian; Prior, Karola; Harmsen, Dag

    2012-06-01

    Neisseria meningitidis causes invasive meningococcal disease in infants, toddlers, and adolescents worldwide. DNA sequence-based typing, including multilocus sequence typing, analysis of genetic determinants of antibiotic resistance, and sequence typing of vaccine antigens, has become the standard for molecular epidemiology of the organism. However, PCR of multiple targets and consecutive Sanger sequencing provide logistic constraints to reference laboratories. Taking advantage of the recent development of benchtop next-generation sequencers (NGSs) and of BIGSdb, a database accommodating and analyzing genome sequence data, we therefore explored the feasibility and accuracy of Ion Torrent Personal Genome Machine (PGM) sequencing for genomic typing of meningococci. Three strains from a previous meningococcus serogroup B community outbreak were selected to compare conventional typing results with data generated by semiconductor chip-based sequencing. In addition, sequencing of the meningococcal type strain MC58 provided information about the general performance of the technology. The PGM technology generated sequence information for all target genes addressed. The results were 100% concordant with conventional typing results, with no further editing being necessary. In addition, the amount of typing information, i.e., nucleotides and target genes analyzed, could be substantially increased by the combined use of genome sequencing and BIGSdb compared to conventional methods. In the near future, affordable and fast benchtop NGS machines like the PGM might enable reference laboratories to switch to genomic typing on a routine basis. This will reduce workloads and rapidly provide information for laboratory surveillance, outbreak investigation, assessment of vaccine preventability, and antibiotic resistance gene monitoring.

  20. How the Knowledge of Interactions between Meningococcus and the Human Immune System Has Been Used to Prepare Effective Neisseria meningitidis Vaccines

    Directory of Open Access Journals (Sweden)

    R. Gasparini

    2015-01-01

    Full Text Available In the last decades, tremendous advancement in dissecting the mechanisms of pathogenicity of Neisseria meningitidis at a molecular level has been achieved, exploiting converging approaches of different disciplines, ranging from pathology to microbiology, immunology, and omics sciences (such as genomics and proteomics. Here, we review the molecular biology of the infectious agent and, in particular, its interactions with the immune system, focusing on both the innate and the adaptive responses. Meningococci exploit different mechanisms and complex machineries in order to subvert the immune system and to avoid being killed. Capsular polysaccharide and lipooligosaccharide glycan composition, in particular, play a major role in circumventing immune response. The understanding of these mechanisms has opened new horizons in the field of vaccinology. Nowadays different licensed meningococcal vaccines are available and used: conjugate meningococcal C vaccines, tetravalent conjugate vaccines, an affordable conjugate vaccine against the N. menigitidis serogroup A, and universal vaccines based on multiple antigens each one with a different and peculiar function against meningococcal group B strains.