WorldWideScience

Sample records for activate multiple types

  1. Endogenous and recombinant type I interferons and disease activity in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Finn Sellebjerg

    Full Text Available Although treatment of multiple sclerosis (MS with the type I interferon (IFN IFN-β lowers disease activity, the role of endogenous type I IFN in MS remains controversial. We studied CD4+ T cells and CD4+ T cell subsets, monocytes and dendritic cells by flow cytometry and analysed the relationship with endogenous type I IFN-like activity, the effect of IFN-β therapy, and clinical and magnetic resonance imaging (MRI disease activity in MS patients. Endogenous type I IFN activity was associated with decreased expression of the integrin subunit CD49d (VLA-4 on CD4+CD26(high T cells (Th1 helper cells, and this effect was associated with less MRI disease activity. IFN-β therapy reduced CD49d expression on CD4+CD26(high T cells, and the percentage of CD4+CD26(high T cells that were CD49d(high correlated with clinical and MRI disease activity in patients treated with IFN-β. Treatment with IFN-β also increased the percentage of CD4+ T cells expressing CD71 and HLA-DR (activated T cells, and this was associated with an increased risk of clinical disease activity. In contrast, induction of CD71 and HLA-DR was not observed in untreated MS patients with evidence of endogenous type IFN I activity. In conclusion, the effects of IFN-β treatment and endogenous type I IFN activity on VLA-4 expression are similar and associated with control of disease activity. However, immune-activating effects of treatment with IFN-β may counteract the beneficial effects of treatment and cause an insufficient response to therapy.

  2. Endogenous and recombinant type I interferons and disease activity in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, Finn; Krakauer, Martin; Limborg, Signe;

    2012-01-01

    with endogenous type I IFN-like activity, the effect of IFN-ß therapy, and clinical and magnetic resonance imaging (MRI) disease activity in MS patients. Endogenous type I IFN activity was associated with decreased expression of the integrin subunit CD49d (VLA-4) on CD4+CD26(high) T cells (Th1 helper cells......Although treatment of multiple sclerosis (MS) with the type I interferon (IFN) IFN-ß lowers disease activity, the role of endogenous type I IFN in MS remains controversial. We studied CD4+ T cells and CD4+ T cell subsets, monocytes and dendritic cells by flow cytometry and analysed the relationship...... the percentage of CD4+ T cells expressing CD71 and HLA-DR (activated T cells), and this was associated with an increased risk of clinical disease activity. In contrast, induction of CD71 and HLA-DR was not observed in untreated MS patients with evidence of endogenous type IFN I activity. In conclusion...

  3. Multiple implantation and multiple annealing of phosphorus doped germanium to achieve n-type activation near the theoretical limit

    Science.gov (United States)

    Kim, Jeehwan; Bedell, Stephen W.; Sadana, Devendra K.

    2012-09-01

    Full activation of n-type dopant in germanium (Ge) reaching to its solid solubility has never been achieved by using ion implantation doping technique. This is because implantation of dopants always leaves defects such as vacancy and interstitials in the Ge crystal. While implantation-induced defects are electrically neutral for the most of semiconductor materials, they are electrically positive for Ge resulting in compensation of n-type dopants. In this Letter, we verified that 5 × 1019 P/cm3 is the maximum active concentration, which can be fully activated in germanium "without leaving implantation damage" per implantation/annealing cycle. The repetition of implantation and annealing of phosphorous (P) with the concentration of 5 × 1019 cm-3 leads to the activation of 1 × 1020 P/cm3 close to its solid solubility limit of 2 × 1020 P/cm3.

  4. Regulatory genomic regions active in immune cell types explain a large proportion of the genetic risk of multiple sclerosis.

    Science.gov (United States)

    Elangovan, Ramyiadarsini I; Disanto, Giulio; Berlanga-Taylor, Antonio J; Ramagopalan, Sreeram V; Handunnetthi, Lahiru

    2014-04-01

    There is little understanding of how genetic variants discovered in recent genome-wide association studies are involved in the pathogenesis of multiple sclerosis (MS). We aimed to investigate which chromatin states and cell types explain genetic risk in MS. We used genotype data from 1854 MS patients and 5164 controls produced by the International Multiple Sclerosis Genetics Consortium and Wellcome Trust Case Control Consortium. We estimated the proportion of phenotypic variance between cases and controls explained by cell-specific chromatin state and DNase I hypersensitivity sites (DHSs) using the Genome-wide Complex Trait Analysis software. A large proportion of variance was explained by single-nucleotide polymorphisms (SNPs) in strong enhancer (SE) elements of immortalized B lymphocytes (5.39%). Three independent SNPs located within SE showed suggestive evidence of association with MS: rs12928822 (odds ratio (OR)=0.81, 95% confidence interval (CI)=0.73-0.89, P=2.48E-05), rs727263 (OR=0.75, 95% CI=0.66-0.85, P=3.26E-06) and rs4674923 (OR=0.85, 95% CI=0.79-0.92, P=1.63E-05). Genetic variants located within DHSs of CD19+ B cells explained the greatest proportion of variance. Genetic variants influencing the risk of MS are located within regulatory elements active in immune cells. This study also identifies a number of immune cell types likely to be involved in the causal cascade and that carry important implications for future studies of therapeutic design.

  5. Elevated type I interferon-like activity in a subset of multiple sclerosis patients: molecular basis and clinical relevance

    Directory of Open Access Journals (Sweden)

    Hundeshagen Alexander

    2012-06-01

    Full Text Available Abstract Background A subset of patients with multiple sclerosis (MS shows an increased endogenous IFN-like activity before initiation of IFN-beta treatment. The molecular basis of this phenomenon and its relevance to predict individual therapy outcomes are not yet fully understood. We studied the expression patterns of these patients, the prognostic value of an elevated IFN-like activity, and the gene regulatory effects of exogenously administered IFN-beta. Methods Microarray gene expression profiling was performed for 61 MS patients using peripheral blood mononuclear cells obtained before and after 1 month of IFN-beta therapy. Expression levels of genes involved in pathways either inducing or being activated by IFN-beta were compared between patients with high (MX1high cohort and low (MX1low cohort endogenous IFN-like activity. Patients were followed for 5 years and relapses as well as progression on the expanded disability status scale (EDSS were documented. Results Before the start of therapy, 11 patients presented elevated mRNA levels of IFN-stimulated genes indicative of a relatively high endogenous IFN-like activity (MX1high. In these patients, pathogen receptors (for example, TLR7, RIG-I and IFIH1 and transcription factors were also expressed more strongly, which could be attributed to an overactivity of IFN-stimulated gene factor 3 (ISGF3, a complex formed by STAT1, STAT2 and IFN regulatory factor 9. After 1 month of IFN-beta therapy, the expression of many pathway genes was significantly induced in MX1low patients, but remained unaltered in MX1high patients. During follow-up, relapse rate and changes in EDSS were comparable between both patient groups, with differences seen between different types of IFN-beta drug application. Conclusions Therapeutic IFN-beta induces the transcription of several genes involved in IFN-related pathways. In a subgroup of MS patients, the expression of these genes is already increased before therapy

  6. Multiple endocrine neoplasia type 2.

    Science.gov (United States)

    Lodish, Maya

    2013-01-01

    Multiple endocrine neoplasia type 2 (MEN2) is an autosomal-dominant cancer syndrome characterized by variable penetrance of medullary thyroid carcinoma(MTC), pheochromocytoma (PHEO), and primary hyperparathyroidism (PHPT). MEN2 consists of two clinical subtypes, MEN2A and MEN2B. Familial medullary thyroid cancer is now viewed as a phenotypic variant of MEN2A with decreased penetrance for PHEO and PHPT rather than a distinct entity. All subtypes are caused by gain-of-function mutations of the RET proto-oncogene. Genotype-phenotype correlations exist that help predict the presence of other associated endocrine neoplasms as well as the timing of thyroid cancer development. Recognition of the clinical entity in individuals and families at risk of harboring a germline RET mutation is crucial for the management and prevention of associated malignancies. Recent guidelines released by the American Thyroid Association regarding the management of MTC will be summarized in this chapter.

  7. Multiple tissue-specific isoforms of sulfatide activate CD1d-restricted type II NKT cells

    DEFF Research Database (Denmark)

    Blomqvist, Maria; Rhost, Sara; Teneberg, Susann;

    2009-01-01

    The glycosphingolipid sulfatide (SO(3)-3Galbeta1Cer) is a demonstrated ligand for a subset of CD1d-restricted NKT cells, which could regulate experimental autoimmune encephalomyelitis, a murine model for multiple sclerosis, as well as tumor immunity and experimental hepatitis. Native sulfatide...... is a mixture of sulfatide isoforms, i.e. sulfatide molecules with different long-chain bases and fatty acid chain lengths and saturation. Here, we demonstrate that sulfatide-specific CD1d-restricted murine NKT hybridomas recognized several different sulfatide isoforms. These included the physiologically...... isoforms by a CD1d-restricted NKT-cell clone, and suggest that sulfatide, a major component of the myelin sheet and pancreatic beta-cells, is one of several natural ligands for type II CD1d-restricted NKT cells....

  8. Evaluation of Am-Li neutron spectra data for active well type neutron multiplicity measurements of uranium

    Science.gov (United States)

    Goddard, Braden; Croft, Stephen; Lousteau, Angela; Peerani, Paolo

    2016-09-01

    Safeguarding nuclear material is an important and challenging task for the international community. One particular safeguards technique commonly used for uranium assay is active neutron correlation counting. This technique involves irradiating unused uranium with (α, n) neutrons from an Am-Li source and recording the resultant neutron pulse signal which includes induced fission neutrons. Although this non-destructive technique is widely employed in safeguards applications, the neutron energy spectra from an Am-Li sources is not well known. Several measurements over the past few decades have been made to characterize this spectrum; however, little work has been done comparing the measured and theoretical spectra of various Am-Li sources to each other. This paper examines fourteen different Am-Li spectra, focusing on how these spectra affect simulated neutron multiplicity results using the code Monte Carlo N-Particle eXtended (MCNPX). Two measurement and simulation campaigns were completed using Active Well Coincidence Counter (AWCC) detectors and uranium standards of varying enrichment. The results of this work indicate that for standard AWCC measurements, the fourteen Am-Li spectra produce similar doubles and triples count rates. The singles count rates varied by as much as 20% between the different spectra, although they are usually not used in quantitative analysis, being dominated by scattering which is highly dependent on item placement.

  9. AtMYB41 activates ectopic suberin synthesis and assembly in multiple plant species and cell types.

    Science.gov (United States)

    Kosma, Dylan K; Murmu, Jhadeswar; Razeq, Fakhria M; Santos, Patricia; Bourgault, Richard; Molina, Isabel; Rowland, Owen

    2014-10-01

    Suberin is a lipid and phenolic cell wall heteropolymer found in the roots and other organs of all vascular plants. Suberin plays a critical role in plant water relations and in protecting plants from biotic and abiotic stresses. Here we describe a transcription factor, AtMYB41 (At4g28110), that can activate the steps necessary for aliphatic suberin synthesis and deposition of cell wall-associated suberin-like lamellae in both Arabidopsis thaliana and Nicotiana benthamiana. Overexpression of AtMYB41 increased the abundance of suberin biosynthetic gene transcripts by orders of magnitude and resulted in the accumulation of up to 22 times more suberin-type than cutin-type aliphatic monomers in leaves. Overexpression of AtMYB41 also resulted in elevated amounts of monolignols in leaves and an increase in the accumulation of phenylpropanoid and lignin biosynthetic gene transcripts. Surprisingly, ultrastructural data indicated that overexpression led to the formation of suberin-like lamellae in both epidermal and mesophyll cells of leaves. We further implicate AtMYB41 in the production of aliphatic suberin under abiotic stress conditions. These results provide insight into the molecular-genetic mechanisms of the biosynthesis and deposition of a ubiquitous cell wall-associated plant structure and will serve as a basis for discovering the transcriptional network behind one of the most abundant lipid-based polymers in nature.

  10. Mating type and ploidy effect on the β-glucosidase activity and ethanol-producing performance of Saccharomyces cerevisiae with multiple δ-integrated bgl1 gene.

    Science.gov (United States)

    Wang, Jianjun; Ma, Yuanyuan; Zhang, Kun; Yang, Huajun; Liu, Cheng; Zou, Shaolan; Hong, Jiefang; Zhang, Minhua

    2016-08-10

    In order to investigate the effect of mating type and ploidy on enzymatic activity and fermentation performance in yeast with multiple δ-integrated foreign genes, eight ploidy series strains were constructed. The initial haploid strain BGL-a was shown to contain about 19 copies of the bgl1 gene. In rich media containing 2% (w/v) sugar the specific activities of BGL-aα were lower than those of BGL-aa or BGL-αα, which indicates the existence of mating type effects. While the maximum OD660 decreased with rising ploidy, the biomass yield showed no significant difference between the eight strains and the specific activities (expressed as U/mL or U/mg DCW) showed little to no variation. When cellobiose was used as the carbon source and β-glucosidase substrate, β-glucosidase was expressed more quickly and at higher levels than in glucose-containing media. The maximum specific activitiy values obtained were 19.07U/mL and 19.39U/mL for BGL-αα and BGL-aa, repsectively. The anaerobic biomass and ethanol-producing performance in rich media containing 10% cellobiose showed no significant difference among the eight strains. Their maximal ethanol concentrations and corresponding yields ranged from 40.27 to 43.46g/L and 77.56 to 83.71%, respectively. When the acid- and alkali-pretreated corncob (10% solids content) was used, the diploid BGL-aα fermented the best. When urea was used as the only supplemented nutrient, the ethanol titer and yield were 35.65g/L and 83.69%, respectively, while a control experiment using industrial Angel yeast with exogenous β-glucosidase addition gave values of 37.93g/L and 89.04%. The combined effects of δ-integration of bgl1, ploidy and mating type result in BGL-aa or BGL-αα being the optimal choice for enzyme production and BGL-aα being more suitable for cellulosic ethanol fermentation. These results provide valuable information for future yeast breeding and utilization efforts.

  11. Parent-child attitude congruence on type and intensity of physical activity: Testing multiple mediators of sedentary behavior in older children

    Science.gov (United States)

    This study examined parent–child attitudes on value of specific types and intensities of physical activity, which may explain gender differences in child activity, and evaluated physical activity as a mechanism to reduce time spent in sedentary behaviors. A community sample of 681 parents and 433 ch...

  12. Type 1 diabetes and multiple sclerosis

    DEFF Research Database (Denmark)

    Nielsen, Nete M; Westergaard, Tine; Frisch, Morten

    2006-01-01

    BACKGROUND: Type 1 diabetes mellitus (T1D) and multiple sclerosis (MS) contribute considerably to the burden of autoimmune diseases in young adults. Although HLA patterns of T1D and MS are considered mutually exclusive, individual and familial co-occurrence of the 2 diseases has been reported...... Multiple Sclerosis Register were used to identify patients with T1D, defined as patients in whom diabetes was diagnosed before age 20 years (N = 6078), and patients with MS (N = 11 862). First-degree relatives (N = 14,771) of patients with MS were identified from family information in the Danish Civil....... OBJECTIVE: To assess the co-occurrence of T1D and MS by estimating the risk for MS in patients with T1D and the risk for T1D in first-degree relatives of patients with MS. DESIGN, SETTING, AND PARTICIPANTS: Two population-based disease registers, the Danish Hospital Discharge Register and the Danish...

  13. Operation characteristics of a multiple type MCFC

    Energy Technology Data Exchange (ETDEWEB)

    Kuroe, S.; Kamo, T. [Hitachi Research Lab., Hitachi, Ltd., Ibaraki-ken (Japan); Fujimura, H.; Kahara, T. [Hitachi, Ltd., Ibaraki-ken (Japan)

    1996-12-31

    Multiple type structure of MCFC of which the separator of the cell is divided by four element cells has been studied. For the stable operation of this type cell, the effect of gas flow rate and temperature distribution on the cell voltage should be clear. In order to clarify these characteristics, a small sized mimic model has been made and tested. The flow rate distribution for the four element cells were varied and cell voltage and temperature distribution were measured for each cell. The decrease in cell voltage and the increase in maximum temperature became remarkable when the apparent utilization factor for one element cell became over 100%. The calculated results agreed fairly good with test results.

  14. Type I interferon drives dendritic cell apoptosis via multiple BH3-only proteins following activation by PolyIC in vivo.

    Directory of Open Access Journals (Sweden)

    Silvia A Fuertes Marraco

    Full Text Available BACKGROUND: DC are activated by pathogen-associated molecular patterns (PAMPs, and this is pivotal for the induction of adaptive immune responses. Thereafter, the clearance of activated DC is crucial to prevent immune pathology. While PAMPs are of major interest for vaccine science due to their adjuvant potential, it is unclear whether and how PAMPs may affect DC viability. We aimed to elucidate the possible apoptotic mechanisms that control activated DC lifespan in response to PAMPs, particularly in vivo. METHODOLOGY/PRINCIPAL FINDINGS: We report that polyinosinic:polycytidylic acid (PolyIC, synthetic analogue of dsRNA induces dramatic apoptosis of mouse splenic conventional DC (cDC in vivo, predominantly affecting the CD8α subset, as shown by flow cytometry-based analysis of splenic DC subsets. Importantly, while Bim deficiency conferred only minor protection, cDC depletion was prevented in mice lacking Bim plus one of three other BH3-only proteins, either Puma, Noxa or Bid. Furthermore, we show that Type I Interferon (IFN is necessary and sufficient for DC death both in vitro and in vivo, and that TLR3 and MAVS co-operate in IFNß production in vivo to induce DC death in response to PolyIC. CONCLUSIONS/SIGNIFICANCE: These results demonstrate for the first time in vivo that apoptosis restricts DC lifespan following activation by PolyIC, particularly affecting the CD8α cDC subset. Such DC apoptosis is mediated by the overlapping action of pro-apoptotic BH3-only proteins, including but not solely involving Bim, and is driven by Type I IFN. While Type I IFNs are important anti-viral factors, CD8α cDC are major cross-presenting cells and critical inducers of CTL. We discuss such paradoxical finding on DC death with PolyIC/Type I IFN. These results could contribute to understand immunosuppression associated with chronic infection, and to the optimization of DC-based therapies and the clinical use of PAMPs and Type I IFNs.

  15. Cellular and molecular mechanisms underlie the anti-tumor activities exerted by Walterinnesia aegyptia venom combined with silica nanoparticles against multiple myeloma cancer cell types.

    Directory of Open Access Journals (Sweden)

    Gamal Badr

    Full Text Available Multiple myeloma (MM is a clonal disease of plasma cells that remains incurable despite the advent of several novel therapeutics. In this study, we aimed to delineate the impact of snake venom extracted from Walterinnesia aegyptia (WEV alone or in combination with silica nanoparticles (WEV+NP on primary MM cells isolated from patients diagnosed with MM as well as on two MM cell lines, U266 and RPMI 8226. The IC(50 values of WEV and WEV+NP that significantly decreased MM cell viability without affecting the viability of normal peripheral mononuclear cells (PBMCs were determined to be 25 ng/ml and 10 ng/ml, respectively. Although both WEV (25 ng/ml and WEV+NP (10 ng/ml decreased the CD54 surface expression without affecting the expression of CXCR4 (CXCL12 receptor on MM cells, they significantly reduced the ability of CXC chemokine ligand 12 (CXCL12 to induce actin cytoskeleton rearrangement and the subsequent reduction in chemotaxis. It has been established that the binding of CXCL12 to its receptor CXCR4 activates multiple intracellular signal transduction pathways that regulate MM cell chemotaxis, adhesion, and proliferation. We found that WEV and WEV+NP clearly decreased the CXCL12/CXCR4-mediated activation of AKT, ERK, NFκB and Rho-A using western blot analysis; abrogated the CXCL12-mediated proliferation of MM cells using the CFSE assay; and induced apoptosis in MM cell as determined by PI/annexin V double staining followed by flow cytometry analysis. Monitoring the expression of B-cell CCL/Lymphoma 2 (Bcl-2 family members and their role in apoptosis induction after treatment with WEV or WEV+NP revealed that the combination of WEV with NP robustly decreased the expression of the anti-apoptotic effectors Bcl-2, Bcl(XL and Mcl-1; conversely increased the expression of the pro-apoptotic effectors Bak, Bax and Bim; and altered the mitochondrial membrane potential in MM cells. Taken together, our data reveal the biological effects of WEV and WEV

  16. Active Learning with Multiple Views

    CERN Document Server

    Knoblock, C A; Muslea, I; 10.1613/jair.2005

    2011-01-01

    Active learners alleviate the burden of labeling large amounts of data by detecting and asking the user to label only the most informative examples in the domain. We focus here on active learning for multi-view domains, in which there are several disjoint subsets of features (views), each of which is sufficient to learn the target concept. In this paper we make several contributions. First, we introduce Co-Testing, which is the first approach to multi-view active learning. Second, we extend the multi-view learning framework by also exploiting weak views, which are adequate only for learning a concept that is more general/specific than the target concept. Finally, we empirically show that Co-Testing outperforms existing active learners on a variety of real world domains such as wrapper induction, Web page classification, advertisement removal, and discourse tree parsing.

  17. Safety, pharmacokinetics, and antiretroviral activity of multiple doses of ibalizumab (formerly TNX-355), an anti-CD4 monoclonal antibody, in human immunodeficiency virus type 1-infected adults.

    Science.gov (United States)

    Jacobson, Jeffrey M; Kuritzkes, Daniel R; Godofsky, Eliot; DeJesus, Edwin; Larson, Jeffrey A; Weinheimer, Steven P; Lewis, Stanley T

    2009-02-01

    Ibalizumab (formerly TNX-355) is a humanized monoclonal antibody that binds CD4, the primary receptor for human immunodeficiency virus type 1 (HIV-1), and inhibits the viral entry process. A phase lb multidose study of the safety, pharmacokinetics, and antiviral activity of ibalizumab was conducted with 22 HIV-1-infected patients. Nineteen patients were randomized to receive either 10 mg/kg of body weight weekly (arm A) or a 10-mg/kg loading dose followed by 6 mg/kg every 2 weeks (arm B) intravenously for 9 weeks. Three patients were assigned to receive 25 mg/kg every 2 weeks for five doses (arm C). During the study, the patients remained off other antiretrovirals or continued a stable failing regimen. Treatment with ibalizumab resulted in substantial reductions in HIV-1 RNA levels (0.5 to 1.7 log(10)) in 20 of 22 subjects. In most patients, HIV-1 RNA fell to nadir levels after 1 to 2 weeks of treatment and then returned to baseline despite continued treatment. Baseline viral isolates were susceptible to ibalizumab in vitro, regardless of coreceptor tropism. Emerging resistance to ibalizumab was manifested by reduced maximal percent inhibition in a single-cycle HIV infectivity assay. Resistant isolates remained CD4 dependent and were susceptible to enfuvirtide in vitro. Complete coating of CD4(+) T-cell receptors was correlated with serum ibalizumab concentrations. There was no evidence of CD4(+) T-cell depletion in ibalizumab-treated patients. Ibalizumab was not immunogenic, and no serious drug-related adverse effects occurred. In conclusion, ibalizumab administered either weekly or biweekly was safe and well tolerated and demonstrated antiviral activity. Further studies with ibalizumab in combination with standard antiretroviral treatments are warranted.

  18. Diabetes Type 2 - Multiple Languages: MedlinePlus

    Science.gov (United States)

    ... Are Here: Home → Multiple Languages → All Health Topics → Diabetes Type 2 URL of this page: https://medlineplus.gov/languages/ ... V W XYZ List of All Topics All Diabetes Type 2 - Multiple Languages To use the sharing features on ...

  19. Multiple-Active Multiple-Passive Antenna Systems and Applications

    DEFF Research Database (Denmark)

    Tsakalaki, Elpiniki

    2013-01-01

    -passive (MAMP) antenna topologies, as explained in Sect. 8.1. Then, Sect. 8.2 proposes MAMP antenna structures with application to reconfigurable MIMO transmission in the presence of antenna mutual coupling under poor scattering channel conditions. For this purpose, the section presents an adaptive MAMP antenna......This chapter focuses on extensions and foreseen applications of the parasitic antenna array technology. Moving beyond the single-active (single-RF) communication setup, hitherto discussed in the previous chapters, the work in this chapter extends the analysis to generalized multiple-active multiple...... adaptive MAMP system can be limited to practical dimensions whereas the passive antennas require no extra RF hardware, thus meeting the cost, space, and power constrains of the users’ mobile terminals. The simulation results show that the adaptive MAMP system, thanks to its “adaptivity”, is able to achieve...

  20. T helper cell type 1 (Th1), Th2 and Th17 responses to myelin basic protein and disease activity in multiple sclerosis

    DEFF Research Database (Denmark)

    Hedegaard, Chris J; Krakauer, Martin; Bendtzen, Klaus

    2008-01-01

    Autoreactive T cells are thought to play an essential role in the pathogenesis of multiple sclerosis (MS). We examined the stimulatory effect of human myelin basic protein (MBP) on mononuclear cell (MNC) cultures from 22 patients with MS and 22 sex-matched and age-matched healthy individuals, and...

  1. Unveiling multiple AGN activity in galaxy mergers

    CERN Document Server

    De Rosa, A; Bogdanovic, T; Decarli, R; Heidt, J; Herrero-Illana, R; Husemann, B; Komossa, S; Kun, E; Loiseau, N; Guainazzi, M; Paragi, Z; Perez-Torres, M; Piconcelli, E; Schawinski, K; Vignali, C

    2016-01-01

    In this paper we present an overview of the MAGNA (Multiple AGN Activity) project aiming at a comprehensive study of multiple supemassive black hole systems. With the main goal to characterize the sources in merging systems at different stages of evolution, we selected a sample of objects optically classified as multiple systems on the basis of emission line diagnostics and started a massive multiband observational campaign. Here we report on the discovery of the exceptionally high AGN density compact group SDSS~J0959+1259. A multiband study suggests that strong interactions are taking place among its galaxies through tidal forces, therefore this system represents a case study for physical mechanisms that trigger nuclear activity and star formation. We also present a preliminary analysis of the multiple AGN system SDSS~J1038+3921.}

  2. Coronal magnetic fields from multiple type II bursts

    Science.gov (United States)

    Honnappa, Vijayakumar; Raveesha, K. H.; Subramanian, K. R.

    Coronal magnetic fields from multiple type II bursts Vijayakumar H Doddamani1*, Raveesha K H2 and Subramanian3 1Bangalore University, Bangalore, Karnataka state, India 2CMR Institute of Technology, Bangalore, Karnataka state, India 3 Retd, Indian Institute of Astrophysics, Bangalore, Karnataka state, India Abstract Magnetic fields play an important role in the astrophysical processes occurring in solar corona. In the solar atmosphere, magnetic field interacts with the plasma, producing abundant eruptive activities. They are considered to be the main factors for coronal heating, particle acceleration and the formation of structures like prominences, flares and Coronal Mass Ejections. The magnetic field in solar atmosphere in the range of 1.1-3 Rsun is especially important as an interface between the photospheric magnetic field and the solar wind. Its structure and time dependent change affects space weather by modifying solar wind conditions, Cho (2000). Type II doublet bursts can be used for the estimation of the strength of the magnetic field at two different heights. Two type II bursts occur sometimes in sequence. By relating the speed of the type II radio burst to Alfven Mach Number, the Alfven speed of the shock wave generating type II radio burst can be calculated. Using the relation between the Alfven speed and the mean frequency of emission, the magnetic field strength can be determined at a particular height. We have used the relative bandwidth and drift rate properties of multiple type II radio bursts to derive magnetic field strengths at two different heights and also the gradient of the magnetic field in the outer corona. The magnetic field strength has been derived for different density factors. It varied from 1.2 to 2.5 gauss at a solar height of 1.4 Rsun. The empirical relation of the variation of the magnetic field with height is found to be of the form B(R) = In the present case the power law index ‘γ’ varied from -3 to -2 for variation of

  3. Capitalization of multiple intelligence types during the biology disciplines

    Directory of Open Access Journals (Sweden)

    Mariana DUMITRU

    2010-05-01

    Full Text Available The study was conducted on a sample of children at the Lăpuş School with classes I-VIII, using the teaching/learning process of the biology disciplines. A key element in applying the theory of Multiple Intelligence in a classroom is knowing the intelligence profile of children. Differentiated teaching approach was designed based on the predominant types of intelligences. For this purpose we used various methods: questionnaire, observation of children as they are given various tasks, interview, development of projects, role play, the biographical method-personal history of child, analysis of activities' results (compositions, drawings, collages, portfolios, debates in pair-groups, and case studies. In child’s profile, (types of intelligences become qualities that we capitalize in training, designing different teaching approach depending on predominant types of intelligences. The results appeared without delay. After a school's year that we worked differently with the children, they have improved school performance and became more interested in the study of biological disciplines thus arousing their curiosity and respect towards life.

  4. Psychosocial Correlates of Empirical Types of Multiple Drug Abusers.

    Science.gov (United States)

    Braucht, G. Nicholas; And Others

    1978-01-01

    Examined subgroups of people in relation to specific types of drugs. Multiple drug clusters identified here yielded six basic drug clusters. Typology of drug abusers was developed by proximity cluster analysis. Set of psychosocial measures was differentially related to use of types of drugs and drug abusers. (Author/BEF)

  5. Evidence of platelet activation in multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Alexander J Steven

    2008-06-01

    Full Text Available Abstract Objective A fatality in one multiple sclerosis (MS patient due to acute idiopathic thrombocytopenic purpura (ITP and a near fatality in another stimulated our interest in platelet function abnormalities in MS. Previously, we presented evidence of platelet activation in a small cohort of treatment-naive MS patients. Methods In this report, 92 normal controls and 33 stable, untreated MS patients were studied. Platelet counts, measures of platelet activation [plasma platelet microparticles (PMP, P-selectin expression (CD62p, circulating platelet microaggragtes (PAg], as well as platelet-associated IgG/IgM, were carried out. In addition, plasma protein S activity was measured. Results Compared to controls, PMP were significantly elevated in MS (p Conclusion Platelets are significantly activated in MS patients. The mechanisms underlying this activation and its significance to MS are unknown. Additional study of platelet activation and function in MS patients is warranted.

  6. Identifying metabolic enzymes with multiple types of association evidence

    Directory of Open Access Journals (Sweden)

    Vitkup Dennis

    2006-03-01

    Full Text Available Abstract Background Existing large-scale metabolic models of sequenced organisms commonly include enzymatic functions which can not be attributed to any gene in that organism. Existing computational strategies for identifying such missing genes rely primarily on sequence homology to known enzyme-encoding genes. Results We present a novel method for identifying genes encoding for a specific metabolic function based on a local structure of metabolic network and multiple types of functional association evidence, including clustering of genes on the chromosome, similarity of phylogenetic profiles, gene expression, protein fusion events and others. Using E. coli and S. cerevisiae metabolic networks, we illustrate predictive ability of each individual type of association evidence and show that significantly better predictions can be obtained based on the combination of all data. In this way our method is able to predict 60% of enzyme-encoding genes of E. coli metabolism within the top 10 (out of 3551 candidates for their enzymatic function, and as a top candidate within 43% of the cases. Conclusion We illustrate that a combination of genome context and other functional association evidence is effective in predicting genes encoding metabolic enzymes. Our approach does not rely on direct sequence homology to known enzyme-encoding genes, and can be used in conjunction with traditional homology-based metabolic reconstruction methods. The method can also be used to target orphan metabolic activities.

  7. Teaching English Accepting Multiple Intelligence Types through Arts

    Directory of Open Access Journals (Sweden)

    Ivana CIMERMANOVÁ

    2013-12-01

    Full Text Available The article discusses the importance of acceptance of the multiple intelligence types as one of the key factor influencing the (language teaching. It focuses mainly on the possibility to introduce art as a source of material for language teaching, providing a wide spectrum of possibilities to introduce different types of activities. The author understands art not only as a source for language teaching/learning but something more than that. For her, the art can be a source for presenting moral and aesthetic values and the material, which will develop learners as a complete personality. The art can bring ethics, culture, history to the language lesson and can help learners to understand the mentality and culture of the target language countr(ies more deeply. The paper is the case study done at the secondary school (1st graders, using some materials and preparing them for achieving the states aim, by the author. This study was a space to learn more about the students’ perception of task based approach, what gave them a chance to experience a shift from ‘teacher-centred’ learning to ‘learner centred’ lesson.

  8. Incremental activity modeling in multiple disjoint cameras.

    Science.gov (United States)

    Loy, Chen Change; Xiang, Tao; Gong, Shaogang

    2012-09-01

    Activity modeling and unusual event detection in a network of cameras is challenging, particularly when the camera views are not overlapped. We show that it is possible to detect unusual events in multiple disjoint cameras as context-incoherent patterns through incremental learning of time delayed dependencies between distributed local activities observed within and across camera views. Specifically, we model multicamera activities using a Time Delayed Probabilistic Graphical Model (TD-PGM) with different nodes representing activities in different decomposed regions from different views and the directed links between nodes encoding their time delayed dependencies. To deal with visual context changes, we formulate a novel incremental learning method for modeling time delayed dependencies that change over time. We validate the effectiveness of the proposed approach using a synthetic data set and videos captured from a camera network installed at a busy underground station.

  9. Thyroid incidentalomas in patients with multiple endocrine neoplasia type 1

    NARCIS (Netherlands)

    Lodewijk, Lutske; Bongers, Pim J.; Kist, Jakob W.; Conemans, Elfi B.; de Laat, Joanne M.; Pieterman, Carla R. C.; van der Horst-Schrivers, Anouk N. A.; Jorna, Ciska; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Rinkes, Inne H. M. Borel; Vriens, Menno R.; Valk, Gerlof D.

    2015-01-01

    Objective: Currently, little is known about the prevalence of thyroid tumors in multiple endocrine neoplasia type 1 (MEN1) patients and it is unclear whether tumorigenesis of these thyroid tumors is MEN1-related. The aim of the study was to assess the prevalence of thyroid incidentalomas in MEN1 pat

  10. Thyroid incidentalomas in patients with multiple endocrine neoplasia type 1

    NARCIS (Netherlands)

    Lodewijk, Lutske; Bongers, Pim J; Kist, Jakob W; Conemans, Elfi B; de Laat, Joanne M; Pieterman, Carla R C; van der Horst-Schrivers, Anouk N A; Jorna, Ciska; Hermus, Ad R; Dekkers, Olaf M; de Herder, Wouter W; Drent, Madeleine L; Bisschop, Peter H; Havekes, Bas; Rinkes, Inne H M Borel; Vriens, Menno R; Valk, Gerlof D.

    2015-01-01

    OBJECTIVE: Currently, little is known about the prevalence of thyroid tumors in multiple endocrine neoplasia type 1 (MEN1) patients and it is unclear whether tumorigenesis of these thyroid tumors is MEN1-related. The aim of the study was to assess the prevalence of thyroid incidentalomas in MEN1 pat

  11. Imaging Finding of Multiple Endocrine Neoplasia Type 1: Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Yum, Tae Jun; Cho, Hee Woo [Dept. of Radiology, Yonsei University, College of Medicine, Seoul (Korea, Republic of)

    2012-08-15

    Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominant inherited syndrome with characteristic clinical and radiological manifestations. Many reports on MEN1 have been published; however, no cases of radiologically diagnosed MEN1 have been reported. Therefore, we report on a radiologically diagnosed case of MEN1 with clinical symptoms of gastroduodenal ulcer.

  12. Clinical case: multiple endocrine neoplasia type 1 (MEN 1

    Directory of Open Access Journals (Sweden)

    A K Lipatenkova

    2012-12-01

    Full Text Available Multiple endocrine neoplasia syndrome type 1 (MEN1, Wermer syndrome – group o а heterogeneous inherited deseases, caused by hyperlasia or neoplasia of several endocrine glands. The phenotype of MEN1 is broad, and over 20 different combinations of endocrine and non-endocrine metabolic manifestations have been described. This case demonstrates multiple formations of endocrine organs, starting non-classical with macroprolactonoma resistant to dopamine agonists therapy, other endocrine disorders developed gradually eventually: hyperparathyreoidism and hypoglycemia caused by pancreas lesions, produced proinsulin in high levels.

  13. Observations of Hierarchical Solar-Type Multiple Star Systems

    CERN Document Server

    Roberts,, Lewis C; Mason, Brian D; Hartkopf, William I; Riddle, Reed L

    2015-01-01

    Twenty multiple stellar systems with solar-type primaries were observed at high angular resolution using the PALM-3000 adaptive optics system at the 5 m Hale telescope. The goal was to complement the knowledge of hierarchical multiplicity in the solar neighborhood by confirming recent discoveries by the visible Robo-AO system with new near-infrared observations with PALM-3000. The physical status of most, but not all, of the new pairs is confirmed by photometry in the Ks band and new positional measurements. In addition, we resolved for the first time five close sub-systems: the known astrometric binary in HIP 17129AB, companions to the primaries of HIP 33555, and HIP 118213, and the companions to the secondaries in HIP 25300 and HIP 101430. We place the components on a color-magnitude diagram and discuss each multiple system individually.

  14. OBSERVATIONS OF HIERARCHICAL SOLAR-TYPE MULTIPLE STAR SYSTEMS

    Energy Technology Data Exchange (ETDEWEB)

    Roberts, Lewis C. Jr. [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena CA 91109 (United States); Tokovinin, Andrei [Cerro Tololo Inter-American Observatory, Casilla 603, La Serena (Chile); Mason, Brian D.; Hartkopf, William I. [U.S. Naval Observatory, 3450 Massachusetts Avenue, NW, Washington, DC 20392-5420 (United States); Riddle, Reed L., E-mail: lewis.c.roberts@jpl.nasa.gov [Division of Physics, Mathematics, and Astronomy, California Institute of Technology, Pasadena, CA 91125 (United States)

    2015-10-15

    Twenty multiple stellar systems with solar-type primaries were observed at high angular resolution using the PALM-3000 adaptive optics system at the 5 m Hale telescope. The goal was to complement the knowledge of hierarchical multiplicity in the solar neighborhood by confirming recent discoveries by the visible Robo-AO system with new near-infrared observations with PALM-3000. The physical status of most, but not all, of the new pairs is confirmed by photometry in the Ks band and new positional measurements. In addition, we resolved for the first time five close sub-systems: the known astrometric binary in HIP 17129AB, companions to the primaries of HIP 33555, and HIP 118213, and the companions to the secondaries in HIP 25300 and HIP 101430. We place the components on a color–magnitude diagram and discuss each multiple system individually.

  15. Multiple endocrine neoplasia type 2: achievements and current challenges

    Directory of Open Access Journals (Sweden)

    Andreas Machens

    2012-01-01

    Full Text Available Incremental advances in medical technology, such as the development of sensitive hormonal assays for routine clinical care, are the drivers of medical progress. This principle is exemplified by the creation of the concept of multiple endocrine neoplasia type 2, encompassing medullary thyroid cancer, pheochromocytoma, and primary hyperparathyroidism, which did not emerge before the early 1960s. This review sets out to highlight key achievements, such as joint biochemical and DNA-based screening of individuals at risk of developing multiple endocrine neoplasia type 2, before casting a spotlight on current challenges which include: (i ill-defined upper limits of calcitonin assays for infants and young children, rendering it difficult to implement the biochemical part of the integrated DNA-based/biochemical concept; (ii our increasingly mobile society in which different service providers are caring for one individual at various stages in the disease process. With familial relationships disintegrating as a result of geographic dispersion, information about the history of the origin family may become sketchy or just unavailable. This is when DNA-based gene tests come into play, confirming or excluding an individual's genetic predisposition to multiple endocrine neoplasia type 2 even before there is any biochemical or clinical evidence of the disease. However, the unrivaled molecular genetic progress in multiple endocrine neoplasia type 2 does not come without a price. Screening may uncover unknown gene sequence variants representing either harmless polymorphisms or pathogenic mutations. In this setting, functional characterization of mutant cells in vitro may generate helpful ancillary evidence with regard to the pathogenicity of gene variants in comparison with established mutations.

  16. Activation of Necroptosis in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Dimitry Ofengeim

    2015-03-01

    Full Text Available Multiple sclerosis (MS, a common neurodegenerative disease of the CNS, is characterized by the loss of oligodendrocytes and demyelination. Tumor necrosis factor α (TNF-α, a proinflammatory cytokine implicated in MS, can activate necroptosis, a necrotic cell death pathway regulated by RIPK1 and RIPK3 under caspase-8-deficient conditions. Here, we demonstrate defective caspase-8 activation, as well as activation of RIPK1, RIPK3, and MLKL, the hallmark mediators of necroptosis, in the cortical lesions of human MS pathological samples. Furthermore, we show that MS pathological samples are characterized by an increased insoluble proteome in common with other neurodegenerative diseases such as Alzheimer’s disease (AD, Parkinson’s disease (PD, and Huntington’s disease (HD. Finally, we show that necroptosis mediates oligodendrocyte degeneration induced by TNF-α and that inhibition of RIPK1 protects against oligodendrocyte cell death in two animal models of MS and in culture. Our findings demonstrate that necroptosis is involved in MS and suggest that targeting RIPK1 may represent a therapeutic strategy for MS.

  17. Hydraulics of a multiple slit-type energy dissipater

    Institute of Scientific and Technical Information of China (English)

    吴建华; 姚莉; 马飞; 吴伟伟

    2014-01-01

    With the constructions of high dam projects in China, the energy dissipation downstream of a dam becomes a serious concern. In this study, a multiple slit-type energy dissipater, with different reduction size slits in the outlet, is developed on the basis of conventional slit-type energy dissipaters, aiming to enhance the energy dissipation through the turbulence and the friction between the different layers of the jet flow and the air entrainment due to the increased surface of the flow to the air. The hydraulic characteristics of the energy dissipater are experimentally investigated by means of three sets of physical models in nine cases, to characterize the geometric parameters with suitable performance. The main concerns are the flow regime, the jet flow trajectory, the energy dissipation, the cavitation characteristics, and the flow choking. The results indicate that the dissipater enjoys a high energy dissipation ratio with suitable hydraulic performance comparing with the conventional slit-type energy dissipaters.

  18. Multiplicity of A-type and related stars

    CERN Document Server

    North, Pierre L

    2013-01-01

    The origin of chemically peculiar stars remains enigmatic, especially regarding their frequency among their "normal" peers. In addition to magnetic fields and rotation, multiplicity may shed light on the question. We mention the main surveys of the three kinds performed so far of intermediate mass stars, either normal or chemically peculiar, magnetic or not: imaging, spectroscopic, and photometric. We also consider the mulitiplicity of red giant stars, since many of them are descendants of A-type stars, through Mermilliod's radial velocity monitoring of open cluster members. We briefly review the orbital properties of binary systems hosting chemically peculiar stars. Some specific objects of special interest are mentioned as deserving further study. Finally, we recall that some binary systems composed of A-type stars are progenitors of Type Ia supernovae, and evoke the potentialities of future surveys like Gaia.

  19. New type of cells with multiple chromosome rearrangements

    Energy Technology Data Exchange (ETDEWEB)

    Aseeva, Elena A. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation); Snigiryova, Galina P. [Russian Scientific Centre of Roentgenology and Radiology, ul. Profsoyuznaya 86, 117997 Moscow (Russian Federation); Neverova, Anna L. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation); Bogomazova, Alexandra N.; Novitskaya, Natalia N.; Khazins, Eva D. [Russian Scientific Centre of Roentgenology and Radiology, ul. Profsoyuznaya 86, 117997 Moscow (Russian Federation); Domracheva, Elena V. [National Research Centre for Hematology, Russian Academy of Medical Sciences, Novozykovsky proezd 4a, 125167 Moscow (Russian Federation)], E-mail: dom@blood.ru

    2010-04-15

    A comparative analysis of the distribution and the frequency of multiaberrant cells (MAC) among lymphocytes in different categories of low dose (up to 0.5 Gy) irradiated people was carried out. The highest MAC frequency was observed in people exposed to {alpha}-radiation (Pu, Rn) and in cosmonauts. This fact allows MAC to be considered as an indicator of a high-energy local exposure. A new type of cells with multiple chromosome rearrangements was discovered in the course of analysis of stable aberrations by the fluorescence in situ hybridization (FISH) method. The biological consequences of MAC formation and possibility of revealing the whole diversity of cells with multiple aberrations by means of modern molecular-cytogenetic methods are discussed.

  20. Application of Foldable Intraocular Lens in Multiple Types of Cataract

    Institute of Scientific and Technical Information of China (English)

    Songtao Yuan; Qinghuai Liu; Qing Jiang; Nanrong Yuan

    2002-01-01

    Objective: To evaluate the clinical results of implantation of foldable intraocular lens inmultiple types of cataract.Methods: This retrospective study comprised 162 eyes of 148 patients undergoingphacoemulsification and implantation of foldable intraocular lens, some of whom under-went combined pars plana vitrectomy or trabeculectomy or silicone oil removal. Theperiod of follow-up was from 3 months to 17 months.Results: There is slight reaction postoperatively in all cases. The postoperative uncorrectedvisual acuites was from 0. 05 to 1.2, patient with 0.6 or above acuity were 70.98%. Aneodymium: YAG capsulotomy was required in 5 eyes. Posterior capsule ruptured in 1eyes, and a PMMA intraocular lens was implanted in ciliary sulcus. In one eye, a lenswas removed because of recurrence of retina detachment.Conclusions: The application of foldable intraocular lens in multiple types of cataract issafe, and there is a slight postoperative reaction. less complications , and fast visualacuity recovery.

  1. Hybrid foraging search: Searching for multiple instances of multiple types of target.

    Science.gov (United States)

    Wolfe, Jeremy M; Aizenman, Avigael M; Boettcher, Sage E P; Cain, Matthew S

    2016-02-01

    This paper introduces the "hybrid foraging" paradigm. In typical visual search tasks, observers search for one instance of one target among distractors. In hybrid search, observers search through visual displays for one instance of any of several types of target held in memory. In foraging search, observers collect multiple instances of a single target type from visual displays. Combining these paradigms, in hybrid foraging tasks observers search visual displays for multiple instances of any of several types of target (as might be the case in searching the kitchen for dinner ingredients or an X-ray for different pathologies). In the present experiment, observers held 8-64 target objects in memory. They viewed displays of 60-105 randomly moving photographs of objects and used the computer mouse to collect multiple targets before choosing to move to the next display. Rather than selecting at random among available targets, observers tended to collect items in runs of one target type. Reaction time (RT) data indicate searching again for the same item is more efficient than searching for any other targets, held in memory. Observers were trying to maximize collection rate. As a result, and consistent with optimal foraging theory, they tended to leave 25-33% of targets uncollected when moving to the next screen/patch. The pattern of RTs shows that while observers were collecting a target item, they had already begun searching memory and the visual display for additional targets, making the hybrid foraging task a useful way to investigate the interaction of visual and memory search.

  2. Metastatic multiple endocrine neoplasia type 1: report of one case

    Science.gov (United States)

    Huang, Cheng; Zhu, Xiaodong; Han, Xu

    2016-01-01

    A 46-year-old Chinese woman was admitted to our hospital because of presence of space-occupying lesions in the liver for 2 months in April, 2015. She had a family history of multiple endocrine neoplasia type 1 (MEN1) and physical examination is unremarkable. Previously, she has performed surgery for primary pituitary tumor in 2002 and radiosurgery for its recurrence. Around December 2014, she suffered from abdominal discomfort associated with regurgitation and gastroscopy revealed “gastroduodenal ulcers”, along with elevated gastrin. Next, both magnetic resonance and computed tomography imaging showed multiple intrahepatic lesions, the PET-CT unveiled uptake pattern of 18F-FDG in duodenum and multiple intrahepatic lesions, resembling the appearance of metastatic gastrinoma. The octreotide scan gave identical results. The parathyroid SPECT scans showed abnormal concentrations of radioactivity in right parathyroid. She also had an elevated serum chromogranin A (CgA) level. There was medical evidence to show that she is metastatic MEN1. Although multiple liver metastases, they were considered to be resectable after MDT consultation. The intraoperative exploration found a 1.5 cm tumor on the surface of the tail of the pancreas, a 12 cm retroperitoneal lipoma and two liver metastases, sized 3.5 cm and 1.5 cm, respectively. All these tumors were completely removed. For pancreatic tumor, pathological findings met the diagnostic criteria of neuroendocrine tumor (NET) (G2). Immunohistochemistry revealed neuroendocrine areas were diffusely positive for ATRX, DAXX, SSR2, SSR5 and CgA. For lipoma, the FISH results were negative for CDK4 and MDM2 genes. Postoperatively, adjuvant therapy with octreotide was applied. This case suggested that, as for metastatic gastrinoma, a potentially curative surgical debulking should be considered when a resection of complete or more than 90% of metastatic lesions along with the primary site could be achieved, which is helpful to control

  3. Primary Hyperparathyroidism in Patients with Multiple Endocrine Neoplasia Type 1

    Directory of Open Access Journals (Sweden)

    Grzegorz Piecha

    2010-01-01

    Full Text Available Primary hyperparathyroidism may occur as a part of an inherited syndrome in a combination with pancreatic endocrine tumours and/or pituitary adenoma, which is classified as Multiple Endocrine Neoplasia type 1 (MEN-1. This syndrome is caused by a germline mutation in MEN-1 gene encoding a tumour-suppressor protein, menin. Primary hyperparathyroidism is the most frequent clinical presentation of MEN-1, which usually appears in the second decade of life as an asymptomatic hypercalcemia and progresses through the next decades. The most frequent clinical presentation of MEN-1-associated primary hyperparathyroidism is bone demineralisation and recurrent kidney stones rarely followed by chronic kidney disease. The aim of this paper is to present the pathomechanism, screening procedures, diagnosis, and management of primary hyperparathyroidism in the MEN-1 syndrome. It also summarises the recent advances in the pharmacological therapy with a new group of drugs—calcimimetics.

  4. Multiple exposure to metals in eight types of welding.

    Science.gov (United States)

    Apostoli, P; Porru, S; Brunelli, E; Alessio, L

    1997-01-01

    This article evaluates multiple exposures to metals in different types of metal welding such as manual metal arc for mild and stainless steel, continuous wire, submerged arc, laser and brazing. Environmental monitoring was carried out in eight different occupational situations and the inductively coupled plasma mass spectrometry technique was adopted in order to characterize exposure to several elements simultaneously and with high accuracy. The results showed that up to 23 elements could be measured. The highest concentrations were found for Al, Mn, Fr, Ni, Cr, Cu and Zn. For some elements such as In, Nd, I, Rb the concentrations were very low. A qualitative and quantitative variation in fume composition was observed at a certain distance from the welding point, which should be to taken into account when evaluating indirect exposures. It would also be possible, with this technique, to identify specific elements in the mixture which could also be measured in biological fluids.

  5. Active debris removal of multiple priority targets

    Science.gov (United States)

    Braun, Vitali; Lüpken, A.; Flegel, S.; Gelhaus, J.; Möckel, M.; Kebschull, C.; Wiedemann, C.; Vörsmann, P.

    2013-05-01

    Today's space debris environment shows major concentrations of objects within distinct orbital regions for nearly all size regimes. The most critical region is found at orbital altitudes near 800 km with high declinations. Within this region many satellites are operated in so called sun-synchronous orbits (SSO). Among those, there are Earth observation, communication and weather satellites. Due to the orbital geometry in SSO, head-on encounters with relative velocities of about 15 km/s are most probable and would thus result in highly energetic collisions, which are often referred to as catastrophic collisions, leading to the complete fragmentation of the participating objects. So called feedback collisions can then be triggered by the newly generated fragments, thus leading to a further population increase in the affected orbital region. This effect is known as the Kessler syndrome.Current studies show that catastrophic collisions are not a major problem today, but will become the main process for debris generation within the SSO region in the near future, even without any further launches. In order to avoid this effect, objects with a major impact on collisional cascading have to be actively removed from the critical region after their end of life. Not having the capability to perform an end-of-life maneuver in order to transfer to a graveyard orbit or to de-orbit, many satellites and rocket bodies would have to be de-orbited within a dedicated mission. In such a mission, a service satellite would perform a de-orbit maneuver, after having docked to a specific target.In this paper, chemical and electric propulsion systems were analysed with the main focus on removing multiple targets within one single mission. The targets were chosen from a previously defined priority list in order to enhance the mission efficiency. Total mission time, ΔV and system mass were identified as key parameters to allow for an evaluation of the different concepts. It was shown that it

  6. Weyl group multiple Dirichlet series of type C

    CERN Document Server

    Beineke, Jennifer; Frechette, Sharon

    2010-01-01

    We develop the theory of Weyl group multiple Dirichlet series for root systems of type C. For an arbitrary root system of rank r and a positive integer n, these are Dirichlet series in r complex variables with analytic continuation and functional equations isomorphic to the associated Weyl group. In type C, they conjecturally arise from the Fourier-Whittaker coefficients of minimal parabolic Eisenstein series on an n-fold metaplectic cover of SO(2r+1). For any odd n, we construct an infinite family of Dirichlet series conjecturally satisfying the above analytic properties. The coefficients of these series are exponential sums built from Gelfand-Tsetlin bases of certain highest weight representations. Previous attempts to define such series by Brubaker, Bump, and Friedberg in [6] and [7] required n to be sufficiently large, so that coefficients could be described by Weyl group orbits. We demonstrate that our construction agrees with that of [6] and [7] in the case where both series are defined, and hence inher...

  7. Cushing’s Syndrome in Multiple Endocrine Neoplasia Type 1

    Science.gov (United States)

    Simonds, William F.; Varghese, Sarah; Marx, Stephen J.; Nieman, Lynnette K.

    2011-01-01

    Summary Objective In patients with multiple endocrine neoplasia type 1 (MEN1), Cushing’s syndrome (CS) from endogenous hypercortisolism can result from pituitary, adrenal, or other endocrine tumors. The purpose of this study was to characterize the range of presentations of CS in a large series of MEN1 patients. Design Retrospective review of NIH Clinical Center inpatient records over an approximately 40 year period. Patients 19 patients (8 males, 11 females) with CS and MEN1. Measurements Biochemical, imaging, surgical, and pathological findings. Results An etiology was determined for 14 of the 19 patients with CS and MEN1: 11 (79%) had Cushing’s disease (CD) and three (21%) had ACTH-independent CS due to adrenal tumors, frequencies indistinguishable from sporadic CS. Three of 11 MEN1 patients with CD (27%) had additional non-ACTH secreting pituitary microadenomas identified at surgery, an incidence 10-fold higher than in sporadic CD. Ninety-one percent of MEN1 patients with CD were cured after surgery. Two of three MEN1 patients with ACTH-independent CS (67%) had adrenocortical carcinoma. One patient with adrenal cancer and another with adrenal adenoma were cured by unilateral adrenalectomy. No case of ectopic ACTH secretion was identified in our patient cohort. The etiology of CS could not be defined in five patients; in three of these, hypercortisolism appeared to resolve spontaneously. Conclusions The tumor multiplicity of MEN1 can be reflected in the anterior pituitary, MEN1-associated ACTH-independent CS may be associated with aggressive adrenocortical disease, and an etiology for CS in MEN1 may be elusive in a substantial minority of patients. PMID:21916912

  8. Preliminary Evidence that Self-Efficacy Predicts Physical Activity in Multiple Sclerosis

    Science.gov (United States)

    Motl, Robert W.; McAuley, Edward; Doerksen, Shawna; Hu, Liang; Morris, Katherine S.

    2009-01-01

    Individuals with multiple sclerosis (MS) are less physically active than nondiseased people. One method for increasing physical activity levels involves the identification of factors that correlate with physical activity and that are modifiable by a well designed intervention. This study examined two types of self-efficacy as cross-sectional and…

  9. Activation of multiple phoneme associates of graphemes in visual word recognition.

    Science.gov (United States)

    Lange, Marielle

    2002-01-01

    One general issue in the domain of visual word recognition is to delineate the nature of readers' knowledge of the print-sound mapping. A more specific question is to determine whether multiple grapheme-phoneme associations are available and activated during the phonological transcoding of a letter string. Evidence for the activation of irregular associations during print-to-sound transcoding, independently from lexical influences, was assessed in a letter detection task by examining performance on target-absent pseudowords. We contrasted two types of pseudowords that could be considered homophone with a real word by application of either grapheme-phoneme correspondence rules or of multiple phonemic activation. Performance on both types of homophones was compared to nonhomophone control pseudowords, strictly equivalent in terms of orthographic similarity to the base words. The finding of a homophony disadvantage for the homophones by multiple activation was interpreted as evidence for multiple phonemic activation in the print-to-sound conversion system.

  10. Safety, Pharmacokinetics, and Antiretroviral Activity of Multiple Doses of Ibalizumab (formerly TNX-355), an Anti-CD4 Monoclonal Antibody, in Human Immunodeficiency Virus Type 1-Infected Adults ▿

    OpenAIRE

    Jacobson, Jeffrey M.; Daniel R Kuritzkes; Godofsky, Eliot; DeJesus, Edwin; Larson, Jeffrey A.; Weinheimer, Steven P.; Lewis, Stanley T.

    2008-01-01

    Ibalizumab (formerly TNX-355) is a humanized monoclonal antibody that binds CD4, the primary receptor for human immunodeficiency virus type 1 (HIV-1), and inhibits the viral entry process. A phase lb multidose study of the safety, pharmacokinetics, and antiviral activity of ibalizumab was conducted with 22 HIV-1-infected patients. Nineteen patients were randomized to receive either 10 mg/kg of body weight weekly (arm A) or a 10-mg/kg loading dose followed by 6 mg/kg every 2 weeks (arm B) intr...

  11. Morbillivirus v proteins exhibit multiple mechanisms to block type 1 and type 2 interferon signalling pathways.

    Directory of Open Access Journals (Sweden)

    Senthil K Chinnakannan

    Full Text Available Morbilliviruses form a closely related group of pathogenic viruses which encode three non-structural proteins V, W and C in their P gene. Previous studies with rinderpest virus (RPV and measles virus (MeV have demonstrated that these non-structural proteins play a crucial role in blocking type I (IFNα/β and type II (IFNγ interferon action, and various mechanisms have been proposed for these effects. We have directly compared four important morbilliviruses, rinderpest (RPV, measles virus (MeV, peste des petits ruminants virus (PPRV and canine distemper virus (CDV. These viruses and their V proteins could all block type I IFN action. However, the viruses and their V proteins had varying abilities to block type II IFN action. The ability to block type II IFN-induced gene transcription correlated with co-precipitation of STAT1 with the respective V protein, but there was no correlation between co-precipitation of either STAT1 or STAT2 and the abilities of the V proteins to block type I IFN-induced gene transcription or the creation of the antiviral state. Further study revealed that the V proteins of RPV, MeV, PPRV and CDV could all interfere with phosphorylation of the interferon-receptor-associated kinase Tyk2, and the V protein of highly virulent RPV could also block the phosphorylation of another such kinase, Jak1. Co-precipitation studies showed that morbillivirus V proteins all form a complex containing Tyk2 and Jak1. This study highlights the ability of morbillivirus V proteins to target multiple components of the IFN signalling pathways to control both type I and type II IFN action.

  12. Surgical treatment of pancreatic endocrine tumors in multiple endocrine neoplasia type 1

    Directory of Open Access Journals (Sweden)

    Marcel Cerqueira Cesar Machado

    Full Text Available Surgical approaches to pancreatic endocrine tumors associated with multiple endocrine neoplasia type 1 may differ greatly from those applied to sporadic pancreatic endocrine tumors. Presurgical diagnosis of multiple endocrine neoplasia type 1 is therefore crucial to plan a proper intervention. Of note, hyperparathyroidism/multiple endocrine neoplasia type 1 should be surgically treated before pancreatic endocrine tumors/multiple endocrine neoplasia type 1 resection, apart from insulinoma. Non-functioning pancreatic endocrine tumors/multiple endocrine neoplasia type 1 >1 cm have a high risk of malignancy and should be treated by a pancreatic resection associated with lymphadenectomy. The vast majority of patients with gastrinoma/multiple endocrine neoplasia type 1 present with tumor lesions at the duodenum, so the surgery of choice is subtotal or total pancreatoduodenectomy followed by regional lymphadenectomy. The usual surgical treatment for insulinoma/multiple endocrine neoplasia type 1 is distal pancreatectomy up to the mesenteric vein with or without spleen preservation, associated with enucleation of tumor lesions in the pancreatic head. Surgical procedures for glucagonomas, somatostatinomas, and vipomas/ multiple endocrine neoplasia type 1 are similar to those applied to sporadic pancreatic endocrine tumors. Some of these surgical strategies for pancreatic endocrine tumors/multiple endocrine neoplasia type 1 still remain controversial as to their proper extension and timing. Furthermore, surgical resection of single hepatic metastasis secondary to pancreatic endocrine tumors/multiple endocrine neoplasia type 1 may be curative and even in multiple liver metastases surgical resection is possible. Hepatic trans-arterial chemo-embolization is usually associated with surgical resection. Liver transplantation may be needed for select cases. Finally, pre-surgical clinical and genetic diagnosis of multiple endocrine neoplasia type 1 syndrome and

  13. Active control of multiple resistive wall modes

    Science.gov (United States)

    Brunsell, P. R.; Yadikin, D.; Gregoratto, D.; Paccagnella, R.; Liu, Y. Q.; Bolzonella, T.; Cecconello, M.; Drake, J. R.; Kuldkepp, M.; Manduchi, G.; Marchiori, G.; Marrelli, L.; Martin, P.; Menmuir, S.; Ortolani, S.; Rachlew, E.; Spizzo, G.; Zanca, P.

    2005-12-01

    A two-dimensional array of saddle coils at Mc poloidal and Nc toroidal positions is used on the EXTRAP T2R reversed-field pinch (Brunsell P R et al 2001 Plasma Phys. Control. Fusion 43 1457) to study active control of resistive wall modes (RWMs). Spontaneous growth of several RWMs with poloidal mode number m = 1 and different toroidal mode number n is observed experimentally, in agreement with linear MHD modelling. The measured plasma response to a controlled coil field and the plasma response computed using the linear circular cylinder MHD model are in quantitive agreement. Feedback control introduces a linear coupling of modes with toroidal mode numbers n, n' that fulfil the condition |n - n'| = Nc. Pairs of coupled unstable RWMs are present in feedback experiments with an array of Mc × Nc = 4 × 16 coils. Using intelligent shell feedback, the coupled modes are generally not controlled even though the field is suppressed at the active coils. A better suppression of coupled modes may be achieved in the case of rotating modes by using the mode control feedback scheme with individually set complex gains. In feedback with a larger array of Mc × Nc = 4 × 32 coils, the coupling effect largely disappears, and with this array, the main internal RWMs n = -11, -10, +5, +6 are all simultaneously suppressed throughout the discharge (7 8 wall times). With feedback there is a two-fold extension of the pulse length, compared to discharges without feedback.

  14. Characterization of multiple isolates of Aspergillus fumigatus from patients: genotype, mating type and invasiveness.

    Science.gov (United States)

    Alvarez-Perez, Sergio; Garcia, Marta E; Bouza, Emilio; Pelaez, Teresa; Blanco, Jose L

    2009-01-01

    The possible co-existence of different genotypes of Aspergillus fumigatus in the same case was studied in five patients colonized or infected by this opportunistic mould. A total of 22 isolates were typed by random amplified polymorphic DNA (RAPD) and microsatellite analysis. Differences in the mating type and invasiveness of the isolates were also considered. The combination of four arbitrary primers used in RAPD typing differentiated all the isolates. In microsatellite analysis, at least two different genotypes were identified in four of the five patients. The 22 isolates showed elastase activity after 10 days of incubation at 37 degrees C in an elastin-containing medium. The presence of strains of compatible mating type was observed in one of the colonized patients and one of the individuals with invasive aspergillosis. Some isolates that belonged to the same genotype in microsatellite analysis were of a different mating type. Taken together, our results suggest that multiple isolates of A. fumigatus obtained from colonized or infected patients may differ not only in their genotypes, but also in their invasiveness and mating types. Furthermore, mating type determination may be of great assistance in differentiating some isolates, as two isolates of different mating type cannot be genotypically identical.

  15. Targeting multiple types of tumors using NKG2D-coated iron oxide nanoparticles

    Science.gov (United States)

    Wu, Ming-Ru; Cook, W. James; Zhang, Tong; Sentman, Charles L.

    2014-11-01

    Iron oxide nanoparticles (IONPs) hold great potential for cancer therapy. Actively targeting IONPs to tumor cells can further increase therapeutic efficacy and decrease off-target side effects. To target tumor cells, a natural killer (NK) cell activating receptor, NKG2D, was utilized to develop pan-tumor targeting IONPs. NKG2D ligands are expressed on many tumor types and its ligands are not found on most normal tissues under steady state conditions. The data showed that mouse and human fragment crystallizable (Fc)-fusion NKG2D (Fc-NKG2D) coated IONPs (NKG2D/NPs) can target multiple NKG2D ligand positive tumor types in vitro in a dose dependent manner by magnetic cell sorting. Tumor targeting effect was robust even under a very low tumor cell to normal cell ratio and targeting efficiency correlated with NKG2D ligand expression level on tumor cells. Furthermore, the magnetic separation platform utilized to test NKG2D/NP specificity has the potential to be developed into high throughput screening strategies to identify ideal fusion proteins or antibodies for targeting IONPs. In conclusion, NKG2D/NPs can be used to target multiple tumor types and magnetic separation platform can facilitate the proof-of-concept phase of tumor targeting IONP development.

  16. Genetic heterogeneity in type 1 Gaucher disease: Multiple genotypes in Ashkenazic and non-Ashkenazic individuals

    Energy Technology Data Exchange (ETDEWEB)

    Tsuji, Shoji; Martin, B.M.; Stubblefield, B.K.; LaMarca, M.E.; Ginns, E.I. (National Institute of Mental Health, Bethesda, MD (USA)); Barranger, J.A. (Childrens Hospital of Los Angeles, CA (USA))

    1988-04-01

    Nucleotide sequence analysis of a genomic clone from an Ashkenazic Jewish patient with type 1 Gaucher disease revealed a single-base mutation (adenosine to guanosine transition) in exon 9 of the glucocerebrosidase gene. This change results in the amino acid substitution of serine for asparagine. Transient expression studies following oligonucleotide-directed mutagenesis of the normal cDNA confirmed that the mutation results in loss of glucocerebrosidase activity. Allele-specific hybridization with oligonucleotide probes demonstrated that this mutation was found exclusively in type 1 phenotype. None of the 6 type 2 patients, 11 type 3 patients, or 12 normal controls had this allele. In contrast, 15 of 24 type 1 patients had one allele with this mutation, and 3 others were homozygous for the mutation. Furthermore, some of the Ashkenazic Jewish type 1 patients had only one allele with this mutation, suggesting that even in this population there is allelic heterozygosity. These findings indicate that there are multiple allelic mutations responsible for type 1 Gaucher disease in both the Jewish and non-Jewish populations. Allelic-specific hybridization demonstrating this mutation in exon 9, used in conjunction with the Nci I restriction fragment length polymorphism described as a marker for neuronopathic Gaucher disease, provides a tool for diagnosis and genetic counseling that is {approx}80% informative in all Gaucher patients studied.

  17. The multiplicity of O-type stars in NGC 2244

    NARCIS (Netherlands)

    Mahy, L.; Rauw, G.; Martins, F.; Gosset, E.; Nazé, Y.; Godart, M.; Sana, H.A.A.; De Becker, M.; Eenens, P.

    2011-01-01

    The investigation of the multiplicity of massive stars is crucial to determine a robust binary fraction but also for understanding the physical properties of these objects. In this contribution, we will present the main results from our long-term spectroscopic survey devoted to the young open cluste

  18. Safety, Pharmacokinetics, and Antiretroviral Activity of Multiple Doses of Ibalizumab (formerly TNX-355), an Anti-CD4 Monoclonal Antibody, in Human Immunodeficiency Virus Type 1-Infected Adults ▿

    Science.gov (United States)

    Jacobson, Jeffrey M.; Kuritzkes, Daniel R.; Godofsky, Eliot; DeJesus, Edwin; Larson, Jeffrey A.; Weinheimer, Steven P.; Lewis, Stanley T.

    2009-01-01

    Ibalizumab (formerly TNX-355) is a humanized monoclonal antibody that binds CD4, the primary receptor for human immunodeficiency virus type 1 (HIV-1), and inhibits the viral entry process. A phase lb multidose study of the safety, pharmacokinetics, and antiviral activity of ibalizumab was conducted with 22 HIV-1-infected patients. Nineteen patients were randomized to receive either 10 mg/kg of body weight weekly (arm A) or a 10-mg/kg loading dose followed by 6 mg/kg every 2 weeks (arm B) intravenously for 9 weeks. Three patients were assigned to receive 25 mg/kg every 2 weeks for five doses (arm C). During the study, the patients remained off other antiretrovirals or continued a stable failing regimen. Treatment with ibalizumab resulted in substantial reductions in HIV-1 RNA levels (0.5 to 1.7 log10) in 20 of 22 subjects. In most patients, HIV-1 RNA fell to nadir levels after 1 to 2 weeks of treatment and then returned to baseline despite continued treatment. Baseline viral isolates were susceptible to ibalizumab in vitro, regardless of coreceptor tropism. Emerging resistance to ibalizumab was manifested by reduced maximal percent inhibition in a single-cycle HIV infectivity assay. Resistant isolates remained CD4 dependent and were susceptible to enfuvirtide in vitro. Complete coating of CD4+ T-cell receptors was correlated with serum ibalizumab concentrations. There was no evidence of CD4+ T-cell depletion in ibalizumab-treated patients. Ibalizumab was not immunogenic, and no serious drug-related adverse effects occurred. In conclusion, ibalizumab administered either weekly or biweekly was safe and well tolerated and demonstrated antiviral activity. Further studies with ibalizumab in combination with standard antiretroviral treatments are warranted. PMID:19015347

  19. Falls and Physical Activity in Persons with Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    J. J. Sosnoff

    2012-01-01

    Full Text Available Objectives. To examine the association between fall history and physical activity using an objective measure of physical activity (i.e., accelerometry in persons with multiple sclerosis. Design. A community-based sample of 75 ambulatory persons with multiple sclerosis volunteered for the investigation. Participants self-reported fall history in the last year, underwent a neurological exam to determine Expanded Disability Status Scale (EDSS score, and wore an accelerometer around the waist for 7 consecutive days to determine physical activity. Results. Overall, 37 persons (49.3% of the sample reported falling in the last year with 28 of the 37 falling more than once. Persons who fell in the last year had a significantly lower number of steps/day than nonfallers (3510 versus 4940 steps/day; P.05. Conclusions. Collectively, the findings suggest that fall history may have little impact on current physical activity levels in persons with multiple sclerosis.

  20. Modulatory mechanisms and multiple functions of somatodendritic A-type K+ channel auxiliary subunits

    Directory of Open Access Journals (Sweden)

    Henry Hungtao Jerng

    2014-03-01

    Full Text Available Auxiliary subunits are non-conducting, modulatory components of the multi-protein ion channel complexes that underlie normal neuronal signaling. They interact with the pore-forming α-subunits to modulate surface distribution, ion conductance, and channel gating properties. For the somatodendritic subthreshold A-type potassium (ISA channel based on Kv4 α-subunits, two types of auxiliary subunits have been extensively studied: Kv channel-interacting proteins (KChIPs and dipeptidyl peptidase-like proteins (DPLPs. KChIPs are cytoplasmic calcium-binding proteins that interact with intracellular portions of the Kv4 subunits, whereas DPLPs are type II transmembrane proteins that associate with the Kv4 channel core. Both KChIPs and DPLPs genes contain multiple start sites that are used by various neuronal populations to drive the differential expression of functionally distinct N-terminal variants. In turn, these N-terminal variants generate tremendous functional diversity across the nervous system. Here, we focus our review on (1 the molecular mechanism underlying the unique properties of different N-terminal variants, (2 the shaping of native ISA properties by the concerted actions of KChIPs and DPLP variants, and (3 the surprising ways that KChIPs and DPLPs coordinate the activity of multiple channels to fine-tune neuronal excitability. Unlocking the unique contributions of different auxiliary subunit N-terminal variants may provide an important opportunity to develop novel targeted therapeutics to treat numerous neurological disorders.

  1. In vitro RBE-LET dependence for multiple particle types

    DEFF Research Database (Denmark)

    Sørensen, Brita Singers; Overgaard, Jens; Bassler, Niels

    2011-01-01

    Background. In vitro RBE values for various high LET radiation types have been determined for many different cell types. Occasionally it is criticized that RBE for a given endpoint cannot be single-value dependent on LET alone, but also on particle species, due to the different dose deposition...... profiles on microscopic scale. Hence LET is not sufficient as a predictor of RBE, and this is one of the motivations for development of radiobiological models which explicitly depend on the detailed particle energy spectrum of the applied radiation field. The aim of the present study is to summarize...... points were collected from 20, four and four publications for V79, CHO and T1, respectively, in total covering 228 RBE values from a broad range of particle species. Results and discussion. All RBE-LET data points demonstrate surprising agreement within the general error band formed by the numerous data...

  2. Diffusional correlations among multiple active sites in a single enzyme.

    Science.gov (United States)

    Echeverria, Carlos; Kapral, Raymond

    2014-04-07

    Simulations of the enzymatic dynamics of a model enzyme containing multiple substrate binding sites indicate the existence of diffusional correlations in the chemical reactivity of the active sites. A coarse-grain, particle-based, mesoscopic description of the system, comprising the enzyme, the substrate, the product and solvent, is constructed to study these effects. The reactive and non-reactive dynamics is followed using a hybrid scheme that combines molecular dynamics for the enzyme, substrate and product molecules with multiparticle collision dynamics for the solvent. It is found that the reactivity of an individual active site in the multiple-active-site enzyme is reduced substantially, and this effect is analyzed and attributed to diffusive competition for the substrate among the different active sites in the enzyme.

  3. Multiple switches in G protein-coupled receptor activation.

    Science.gov (United States)

    Ahuja, Shivani; Smith, Steven O

    2009-09-01

    The activation mechanism of G protein-coupled receptors has presented a puzzle that finally may be close to solution. These receptors have a relatively simple architecture consisting of seven transmembrane helices that contain just a handful of highly conserved amino acids, yet they respond to light and a range of chemically diverse ligands. Recent NMR structural studies on the active metarhodopsin II intermediate of the visual receptor rhodopsin, along with the recent crystal structure of the apoprotein opsin, have revealed multiple structural elements or 'switches' that must be simultaneously triggered to achieve full activation. The confluence of several required structural changes is an example of "coincidence counting", which is often used by nature to regulate biological processes. In ligand-activated G protein-coupled receptors, the presence of multiple switches may provide an explanation for the differences between full, partial and inverse agonists.

  4. Epstein-Barr virus and disease activity in multiple sclerosis

    NARCIS (Netherlands)

    D. Buljevac (Dragan); H.Z. Flach (Zwenneke); J. Groen (Jan); P.A. van Doorn (Pieter); F.G.A. van der Meché (Frans); R.Q. Hintzen (Rogier); W.C.J. Hop (Wim); A.D.M.E. Osterhaus (Albert); G.J.J. van Doornum (Gerard)

    2005-01-01

    textabstractOBJECTIVES: To study in relapsing-remitting (RR) multiple sclerosis (MS) whether exacerbations and brain activity as measured by magnetic resonance imaging (MRI) are associated with plasma levels of anti-Epstein Barr (EBV) antibodies and EBV DNA. METHODS: This was a prospective study wit

  5. Multiple strategies to activate gold nanoparticles as antibiotics

    Science.gov (United States)

    Zhao, Yuyun; Jiang, Xingyu

    2013-08-01

    Widespread antibiotic resistance calls for new strategies. Nanotechnology provides a chance to overcome antibiotic resistance by multiple antibiotic mechanisms. This paper reviews the progress in activating gold nanoparticles with nonantibiotic or antibiotic molecules to combat bacterial resistance, analyzes the gap between experimental achievements and real clinical application, and suggests some potential directions in developing antibacterial nanodrugs.

  6. Classifying sows' activity types from acceleration patterns

    DEFF Research Database (Denmark)

    Cornou, Cecile; Lundbye-Christensen, Søren

    2008-01-01

    -dimensional axes, plus the length of the acceleration vector) are selected for each activity. Each time series is modeled using a Dynamic Linear Model with cyclic components. The classification method, based on a Multi-Process Kalman Filter (MPKF), is applied to a total of 15 times series of 120 observations......An automated method of classifying sow activity using acceleration measurements would allow the individual sow's behavior to be monitored throughout the reproductive cycle; applications for detecting behaviors characteristic of estrus and farrowing or to monitor illness and welfare can be foreseen....... This article suggests a method of classifying five types of activity exhibited by group-housed sows. The method involves the measurement of acceleration in three dimensions. The five activities are: feeding, walking, rooting, lying laterally and lying sternally. Four time series of acceleration (the three...

  7. Physical Activity and Type 1 Diabetes

    Science.gov (United States)

    Colberg, Sheri R.; Laan, Remmert; Dassau, Eyal; Kerr, David

    2015-01-01

    While being physically active bestows many health benefits on individuals with type 1 diabetes, their overall blood glucose control is not enhanced without an effective balance of insulin dosing and food intake to maintain euglycemia before, during, and after exercise of all types. At present, a number of technological advances are already available to insulin users who desire to be physically active with optimal blood glucose control, although a number of limitations to those devices remain. In addition to continued improvements to existing technologies and introduction of new ones, finding ways to integrate all of the available data to optimize blood glucose control and performance during and following exercise will likely involve development of “smart” calculators, enhanced closed-loop systems that are able to use additional inputs and learn, and social aspects that allow devices to meet the needs of the users. PMID:25568144

  8. Exact multiplicity of solutions to perturbed logistic type equations on a symmetric domain

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    We apply the imperfect bifurcation theory in Banach spaces to study the exact multiplicity of solutions to a perturbed logistic type equations on a symmetric spatial domain. We obtain the precise bifurcation diagrams.

  9. Exact multiplicity of solutions to perturbed logistic type equations on a symmetric domain

    Institute of Scientific and Technical Information of China (English)

    LIU Ping; SHI JunPing; WANG YuWen

    2008-01-01

    We apply the imperfect bifurcation theory in Banach spaces to study the exact multiplicity of solutions to a perturbed logistic type equations on a symmetric spatial domain.We obtain the precise bifurcation diagrams.

  10. MULTIPLE POSITIVE SOLUTIONS TO A SYSTEM OF NONLINEAR HAMMERSTEIN TYPE INTEGRAL EQUATIONS

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    In this paper, we use cone theory and a new method of computation of fixed point index to study a system of nonlinear Hammerstein type integral equations, and the existence of multiple positive solutions to the system is discussed.

  11. Multiple solid pilocytic astrocytomas in cerebleiium with neurofibromatosis type: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Seo Young; Kim, Myung Soon; Kim, Young Ju [Dept. of Radiology, Yonsei University Wonju College of Medicine, Wonju Severance Christian Hospital, Wonju (Korea, Republic of)

    2014-02-15

    Pilocytic astrocytoma usually has a classic imaging manifestation of a solitary, cyst-like mass with a strong contrast-enhancing mural nodule. There is only one published report so far of multiple solid and cyst type pilocytic astrocytomas in the cerebellum in neurofibromatosis type 1 (NF1) patient from the United States in 2007. We report a case of pilocytic astrocytoma presenting with only solid, multiple pilocytic astrocytomas in the cerebellum in NF1 patient.

  12. A new association – multiple endocrine neoplasia type 1 and malignant peripheral nerve sheath tumor

    OpenAIRE

    Preda, Veronica; Sywak, Mark; Learoyd, Diana

    2014-01-01

    Key Clinical Message We report a patient with multiple endocrine neoplasia type 1 (MEN-1) and an aggressive malignant peripheral nerve sheath tumor (MPNST) arising from a ganglioneuroma of the adrenal gland. Patients with MEN-1 require careful consideration of other tumor associations, including MPNST, as it can portend a poor prognosis. MEN-1 and MPNST have not been reported. We report a patient with multiple endocrine neoplasia type 1 (MEN-1) and an aggressive malignant peripheral nerve she...

  13. Randomized, Double-Blinded, Double-Dummy, Active-Controlled, and Multiple-Dose Clinical Study Comparing the Efficacy and Safety of Mulberry Twig (Ramulus Mori, Sangzhi Alkaloid Tablet and Acarbose in Individuals with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Mengyi Li

    2016-01-01

    Full Text Available Aims. To evaluate the efficacy and safety of mulberry twig alkaloid (SZ-A tablet compared with acarbose in patients with type 2 diabetes. Methods. This clinical trial enrolled 38 patients who were randomized into two groups (SZ-A: 23; acarbose: 15 and were treated for 24 weeks. Patients and clinical trial staffs were masked to treatment assignment throughout the study. The primary outcome measures were glycated hemoglobin (HbA1c and 1-hour and 2-hour postprandial and fasting plasma glucose levels from baseline to the end of treatment. Analysis included all patients who completed this study. Results. By the end of this study, HbA1c level in SZ-A group was decreased from baseline significantly (P<0.001. No significant difference was found when compared with acarbose group (P=0.652. Similarly, 1-hour and 2-hour postprandial plasma glucose levels in SZ-A group were decreased from baseline statistically (P<0.05, without any significant differences compared with acarbose group (P=0.748 and 0.558, resp.. The fasting plasma glucose levels were not significantly changed in both groups. One of 23 patients in SZ-A group (4.76% and 5 of 15 patients in acarbose group (33.33% suffered from gastrointestinal adverse events. Conclusions. Compared with acarbose, SZ-A tablet was effective and safe in glycemic control in patients with type 2 diabetes.

  14. Multiple benefits of targeting inflammation in the treatment of type 2 diabetes.

    Science.gov (United States)

    Donath, Marc Y

    2016-04-01

    The association between the metabolic syndrome and a pathological activation of the innate immune system is now well established. Thus, defective insulin secretion and action are due, at least in part, to islet, liver and fat inflammation in type 2 diabetes. Furthermore, an inflammatory process also seems to be involved in the development of cardiovascular, renal and ophthalmological complications of this disease. Interestingly, several other inflammatory diseases are associated with the metabolic syndrome, such as psoriasis, gout and rheumatic arthritis. The aim of this review is to discuss the clinical progress of anti-inflammatory drugs in the treatment of type 2 diabetes and then speculate on the possible further development of these drugs, with the aim of using the drugs in combination in order to combat the multiple manifestations of inflammatory diseases. This review summarises a presentation given at the 'Islet inflammation in type 2 diabetes' symposium at the 2015 annual meeting of the EASD. It is accompanied by two other reviews on topics from this symposium (by Simone Baltrusch, DOI: 10.1007/s00125-016-3891-x , and Jerry Nadler and colleagues, DOI: 10.1007/s00125-016-3890-y ) and a commentary by the Session Chair, Piero Marchetti (DOI: 10.1007/s00125-016-3875-x ).

  15. High frequency of multiple HPV types in cervical specimens from Danish women

    DEFF Research Database (Denmark)

    Mejlhede, Nina; Bonde, Jesper; Fomsgaard, Anders

    2009-01-01

    Genital human papillomavirus infection (HPV) is common and usually harmless. However, chronic cervical infection with high-risk HPV types can cause cell changes that may eventually lead to cancer. To determine the frequency of individual HPV types among mixed infections, we examined the type...... distribution among cervical specimens from more than 1000 Danish women. We also examined the HPV type distribution and the frequency of single and multiple HPV types for specimens from 113 women who underwent conization and were diagnosed with cervical intraepithelial neoplasia grade II or worse (CIN2+). Using...... microarray technology, we found that 49% of the HPV-positive patients were infected with multiple HPV types. Among the CIN2+ diagnosed women, this frequency was 41%. The most frequently found high-risk HPV type was HPV-16, which was found in 25% of the HPV-positive cervical specimens. Among the HPV positive...

  16. Mining Emerging Patterns for Recognizing Activities of Multiple Users in Pervasive Computing

    DEFF Research Database (Denmark)

    Gu, Tao; Wu, Zhanqing; Wang, Liang;

    2009-01-01

    Understanding and recognizing human activities from sensor readings is an important task in pervasive computing. Existing work on activity recognition mainly focuses on recognizing activities for a single user in a smart home environment. However, in real life, there are often multiple inhabitants...... activity models, and propose an Emerging Pattern based Multi-user Activity Recognizer (epMAR) to recognize both single-user and multiuser activities. We conduct our empirical studies by collecting real-world activity traces done by two volunteers over a period of two weeks in a smart home environment...... sensor readings in a home environment, and propose a novel pattern mining approach to recognize both single-user and multi-user activities in a unified solution. We exploit Emerging Pattern – a type of knowledge pattern that describes significant changes between classes of data – for constructing our...

  17. Longitudinal associations between activity and cognition vary by age, activity type, and cognitive domain.

    Science.gov (United States)

    Bielak, Allison A M; Gerstorf, Denis; Anstey, Kaarin J; Luszcz, Mary A

    2014-12-01

    The demonstration of correlated change is critical to understanding the relationship between activity engagement and cognitive functioning in older adulthood. Changes in activity have been shown to be related to changes in cognition, but little attention has been devoted to how this relationship may vary between specific activity types, cognitive domains, and age groups. Participants initially aged 65-98 years (M = 77.46 years) from the Australian Longitudinal Study of Ageing (n = 1,321) completed measurements of activity (i.e., cognitive, group social, one-on-one social, and physical) and cognition (i.e., perceptual speed, and immediate and delayed episodic memory) at baseline, 2, 8, 11, and 15 years later. Bivariate latent growth curve models covarying for education, sex, and baseline age and medical conditions revealed multiple positive-level relations between activity and cognitive performance, but activity level was not related to later cognitive change. Change in perceptual speed over 15 years was positively associated with change in cognitive activity, and change in immediate episodic memory was positively associated with change in one-on-one social activity. Old-old adults showed a stronger change-change covariance for mentally stimulating activity in relation to perceptual speed than did young-old adults. The differentiation by activity type, cognitive domain, and age contributes to the growing evidence that there is variation in the way cognitive ability at different ages is related to activity.

  18. On asymptotics of t-type regression estimation in multiple linear model

    Institute of Scientific and Technical Information of China (English)

    2004-01-01

    We consider a robust estimator (t-type regression estimator) of multiple linear regression model by maximizing marginal likelihood of a scaled t-type error t-distribution.The marginal likelihood can also be applied to the de-correlated response when the withinsubject correlation can be consistently estimated from an initial estimate of the model based on the independent working assumption. This paper shows that such a t-type estimator is consistent.

  19. Equid herpesvirus type 1 activates platelets.

    Directory of Open Access Journals (Sweden)

    Tracy Stokol

    Full Text Available Equid herpesvirus type 1 (EHV-1 causes outbreaks of abortion and neurological disease in horses. One of the main causes of these clinical syndromes is thrombosis in placental and spinal cord vessels, however the mechanism for thrombus formation is unknown. Platelets form part of the thrombus and amplify and propagate thrombin generation. Here, we tested the hypothesis that EHV-1 activates platelets. We found that two EHV-1 strains, RacL11 and Ab4 at 0.5 or higher plaque forming unit/cell, activate platelets within 10 minutes, causing α-granule secretion (surface P-selectin expression and platelet microvesiculation (increased small events double positive for CD41 and Annexin V. Microvesiculation was more pronounced with the RacL11 strain. Virus-induced P-selectin expression required plasma and 1.0 mM exogenous calcium. P-selectin expression was abolished and microvesiculation was significantly reduced in factor VII- or X-deficient human plasma. Both P-selectin expression and microvesiculation were re-established in factor VII-deficient human plasma with added purified human factor VIIa (1 nM. A glycoprotein C-deficient mutant of the Ab4 strain activated platelets as effectively as non-mutated Ab4. P-selectin expression was abolished and microvesiculation was significantly reduced by preincubation of virus with a goat polyclonal anti-rabbit tissue factor antibody. Infectious virus could be retrieved from washed EHV-1-exposed platelets, suggesting a direct platelet-virus interaction. Our results indicate that EHV-1 activates equine platelets and that α-granule secretion is a consequence of virus-associated tissue factor triggering factor X activation and thrombin generation. Microvesiculation was only partly tissue factor and thrombin-dependent, suggesting the virus causes microvesiculation through other mechanisms, potentially through direct binding. These findings suggest that EHV-1-induced platelet activation could contribute to the thrombosis

  20. Nitric oxide synthase expression and enzymatic activity in multiple sclerosis

    DEFF Research Database (Denmark)

    Broholm, H; Andersen, B; Wanscher, B

    2004-01-01

    We used post-mortem magnetic resonance imaging (MRI) guidance to obtain paired biopsies from the brains of four patients with clinical definite multiple sclerosis (MS). Samples were analyzed for the immunoreactivity (IR) of the three nitric oxide (NO) synthase isoforms [inducible, neuronal...... and endothelial nitric oxide synthase (NOS)], and enzymatic NO synthase activity. MRI guided biopsies documented more active plaques than macroscopic examination, and histological examination revealed further lesions. Inducible NOS (iNOS) was the dominant IR isoform, while reactive astrocytes were the dominant i......NOS expressing cells in active lesions. NOS IR expressing cells were widely distributed in plaques, in white and gray matter that appeared normal macroscopically, and on MR. Endothelial NOS (eNOS) was highly expressed in intraparenchymal vascular endothelial cells of MS patients. A control group matched for age...

  1. An integrated economic model of multiple types and uses of water

    Science.gov (United States)

    Luckmann, Jonas; Grethe, Harald; McDonald, Scott; Orlov, Anton; Siddig, Khalid

    2014-05-01

    Water scarcity is an increasing problem in many parts of the world and the management of water has become an important issue on the political economy agenda in many countries. As water is used in most economic activities and the allocation of water is often a complex problem involving different economic agents and sectors, Computable General Equilibrium (CGE) models have been proven useful to analyze water allocation problems, although their adaptation to include water is still relatively undeveloped. This paper provides a description of an integrated water-focused CGE model (STAGE_W) that includes multiple types and uses of water, and for the first time, the reclamation of wastewater as well as the provision of brackish groundwater as separate, independent activities with specific cost structures. The insights provided by the model are illustrated with an application to the Israeli water sector assuming that freshwater resources available to the economy are cut by 50%. We analyze how the Israeli economy copes with this shock if it reduces potable water supply compared with further investments in the desalination sector. The results demonstrate that the effects on the economy are slightly negative under both scenarios. Counter intuitively, the provision of additional potable water to the economy through desalination does not substantively reduce the negative outcomes. This is mainly due to the high costs of desalination, which are currently subsidized, with the distribution of the negative welfare effect over household groups dependent on how these subsidies are financed.

  2. Multiple host kinases contribute to Akt activation during Salmonella infection.

    Science.gov (United States)

    Roppenser, Bernhard; Kwon, Hyunwoo; Canadien, Veronica; Xu, Risheng; Devreotes, Peter N; Grinstein, Sergio; Brumell, John H

    2013-01-01

    SopB is a type 3 secreted effector with phosphatase activity that Salmonella employs to manipulate host cellular processes, allowing the bacteria to establish their intracellular niche. One important function of SopB is activation of the pro-survival kinase Akt/protein kinase B in the infected host cell. Here, we examine the mechanism of Akt activation by SopB during Salmonella infection. We show that SopB-mediated Akt activation is only partially sensitive to PI3-kinase inhibitors LY294002 and wortmannin in HeLa cells, suggesting that Class I PI3-kinases play only a minor role in this process. However, depletion of PI(3,4) P2/PI(3-5) P3 by expression of the phosphoinositide 3-phosphatase PTEN inhibits Akt activation during Salmonella invasion. Therefore, production of PI(3,4) P2/PI(3-5) P3 appears to be a necessary event for Akt activation by SopB and suggests that non-canonical kinases mediate production of these phosphoinositides during Salmonella infection. We report that Class II PI3-kinase beta isoform, IPMK and other kinases identified from a kinase screen all contribute to Akt activation during Salmonella infection. In addition, the kinases required for SopB-mediated activation of Akt vary depending on the type of infected host cell. Together, our data suggest that Salmonella has evolved to use a single effector, SopB, to manipulate a remarkably large repertoire of host kinases to activate Akt for the purpose of optimizing bacterial replication in its host.

  3. Multiple host kinases contribute to Akt activation during Salmonella infection.

    Directory of Open Access Journals (Sweden)

    Bernhard Roppenser

    Full Text Available SopB is a type 3 secreted effector with phosphatase activity that Salmonella employs to manipulate host cellular processes, allowing the bacteria to establish their intracellular niche. One important function of SopB is activation of the pro-survival kinase Akt/protein kinase B in the infected host cell. Here, we examine the mechanism of Akt activation by SopB during Salmonella infection. We show that SopB-mediated Akt activation is only partially sensitive to PI3-kinase inhibitors LY294002 and wortmannin in HeLa cells, suggesting that Class I PI3-kinases play only a minor role in this process. However, depletion of PI(3,4 P2/PI(3-5 P3 by expression of the phosphoinositide 3-phosphatase PTEN inhibits Akt activation during Salmonella invasion. Therefore, production of PI(3,4 P2/PI(3-5 P3 appears to be a necessary event for Akt activation by SopB and suggests that non-canonical kinases mediate production of these phosphoinositides during Salmonella infection. We report that Class II PI3-kinase beta isoform, IPMK and other kinases identified from a kinase screen all contribute to Akt activation during Salmonella infection. In addition, the kinases required for SopB-mediated activation of Akt vary depending on the type of infected host cell. Together, our data suggest that Salmonella has evolved to use a single effector, SopB, to manipulate a remarkably large repertoire of host kinases to activate Akt for the purpose of optimizing bacterial replication in its host.

  4. Hot Resistance Estimation for Dry Type Transformer Using Multiple Variable Regression, Multiple Polynomial Regression and Soft Computing Techniques

    Directory of Open Access Journals (Sweden)

    M. Srinivasan

    2012-01-01

    Full Text Available Problem statement: This study presents a novel method for the determination of average winding temperature rise of transformers under its predetermined field operating conditions. Rise in the winding temperature was determined from the estimated values of winding resistance during the heat run test conducted as per IEC standard. Approach: The estimation of hot resistance was modeled using Multiple Variable Regression (MVR, Multiple Polynomial Regression (MPR and soft computing techniques such as Artificial Neural Network (ANN and Adaptive Neuro Fuzzy Inference System (ANFIS. The modeled hot resistance will help to find the load losses at any load situation without using complicated measurement set up in transformers. Results: These techniques were applied for the hot resistance estimation for dry type transformer by using the input variables cold resistance, ambient temperature and temperature rise. The results are compared and they show a good agreement between measured and computed values. Conclusion: According to our experiments, the proposed methods are verified using experimental results, which have been obtained from temperature rise test performed on a 55 kVA dry-type transformer.

  5. Activities-specific balance confidence in people with multiple sclerosis.

    Science.gov (United States)

    Nilsagård, Ylva; Carling, Anna; Forsberg, Anette

    2012-01-01

    Objective. To evaluate the validity of the Activities-specific Balance Confidence scale (ABC) in people with multiple sclerosis (PwMS). Design. A multicentre, cross-sectional study. Setting. Six rural and urban Swedish sites, including specialized units at hospitals and primary care centers. Participants. A sample of 84 PwMS with subjective gait and balance impairment but still able to walk 100 m (comparable with EDSS 1-6). Outcome Measures. Timed Up and Go, Timed Up and Go(cog), 25-foot Timed Walk Test, Four Square Step Test, Dynamic Gait Index, Chair Stand Test, 12-item MS Walking Scale, self-reported falls, and use of assistive walking device were used for validation. Results. The concurrent convergent validity was moderate to good (0.50 to -0.75) with the highest correlation found for the 12-item MS Walking Scale. The ABC discriminated between multiple fallers and nonfallers but not between men and women. Ecological validity is suggested since ABC discriminated between users of assistive walking device and nonusers. The internal consistency was high at α = 0.95, and interitem correlations were between 0.30 and 0.83. Conclusion. This study supports the validity of the ABC for persons with mild-to-moderate MS. The participants lacked balance confidence in many everyday activities, likely restricting their participation in society.

  6. Multiple Activities of Punica granatum Linne against Acne Vulgaris.

    Science.gov (United States)

    Lee, Chia-Jung; Chen, Lih-Geeng; Liang, Wen-Li; Wang, Ching-Chiung

    2017-01-12

    Acne is a common skin condition with sebum overproduction, hyperkeratosis, Propionibacterium acnes (P. acnes) and Staphylococcus aureus, and inflammation. Punica granatum (pomegranate) is well-known for its anti-inflammatory effects; however, few studies have discussed the anti-acne effects of pomegranate. In this study, we found that pomegranate extract (PG-E) significantly reduced P. acnes-induced edema in Wistar rat ears. Therefore, an evaluation platform using multiple pathogenic mechanisms of acne was established to explore the anti-acne effects of pomegranate. Results showed that PG-E inhibited bacterial growth and lipase activity. Through a bioguided-fractionation-isolation system, four hydrolysable tannins, punicalagin (1), punicalin (2), strictinin A (3), and granatin B (4), were isolated. Compounds 1 and 2 had greater anti-bacterial activities and anti-testosterone-induced HaCaT proliferative effects than the others. Compounds 1, 3, and 4 displayed lipase inhibitory effects. Compound 4 decreased cyclooxygenase-2 expression and downregulated prostaglandin E₂ production in heat-killed P. acnes-treated RAW 246.7 cells. In conclusion, PG-E is abundant in hydrolysable tannins that display multiple anti-acne capacities, including anti-bacterial, anti-lipase, anti-keratinocyte proliferation, and anti-inflammatory actions. Hence, PG-E has great potential in the application of anti-acne and skin-care products, and punicalagin (1), the most effective component in PG-E, can be employed as a quality control marker.

  7. Multiple Activities of Punica granatum Linne against Acne Vulgaris

    Science.gov (United States)

    Lee, Chia-Jung; Chen, Lih-Geeng; Liang, Wen-Li; Wang, Ching-Chiung

    2017-01-01

    Acne is a common skin condition with sebum overproduction, hyperkeratosis, Propionibacterium acnes (P. acnes) and Staphylococcus aureus, and inflammation. Punica granatum (pomegranate) is well-known for its anti-inflammatory effects; however, few studies have discussed the anti-acne effects of pomegranate. In this study, we found that pomegranate extract (PG-E) significantly reduced P. acnes-induced edema in Wistar rat ears. Therefore, an evaluation platform using multiple pathogenic mechanisms of acne was established to explore the anti-acne effects of pomegranate. Results showed that PG-E inhibited bacterial growth and lipase activity. Through a bioguided-fractionation-isolation system, four hydrolysable tannins, punicalagin (1), punicalin (2), strictinin A (3), and granatin B (4), were isolated. Compounds 1 and 2 had greater anti-bacterial activities and anti-testosterone-induced HaCaT proliferative effects than the others. Compounds 1, 3, and 4 displayed lipase inhibitory effects. Compound 4 decreased cyclooxygenase-2 expression and downregulated prostaglandin E2 production in heat-killed P. acnes-treated RAW 246.7 cells. In conclusion, PG-E is abundant in hydrolysable tannins that display multiple anti-acne capacities, including anti-bacterial, anti-lipase, anti-keratinocyte proliferation, and anti-inflammatory actions. Hence, PG-E has great potential in the application of anti-acne and skin-care products, and punicalagin (1), the most effective component in PG-E, can be employed as a quality control marker. PMID:28085116

  8. Osteoporosis in Multiple Endocrine Neoplasia Type I: A Case Report – Case Report

    Directory of Open Access Journals (Sweden)

    Kurtuluş Kaya

    2008-08-01

    Full Text Available Multiple Endocrine Neoplasia type I (MEN type-I is a rare autosomal dominant hereditary cancer syndrome presented mostly by tumours of the parathyroids, endocrine pancreas and anterior pituitary. Primary hyperparathyroidism is the most common clinical expression in affected patients, present in more than 90% of cases. Osteoporosis is a frequent and early complication of primary hyperparathyroidism in MEN type I. A case with a diagnosis of MEN type-I, 39 years old, presented with humeral, femural and L4 vertebral fractures after falling is evaluated in the view of the literature in this case report. (From the World of Osteoporosis 2008;14:40-3

  9. A Based-Bottleneck Multiple Vehicle Type Dynamic Marginal Cost Model and Algorithm

    Directory of Open Access Journals (Sweden)

    Shuguang Li

    2012-09-01

    Full Text Available Single vehicle type dynamic marginal cost model is extended to multiple vehicle type dynamic one based on time-dependent multiple vehicle type queue analysis at a bottleneck. A dynamic link model is presented to model interactions between cars and trucks, given the link consists of two distinct segments. The first segment is the running segment on which cars (trucks run at their free-flow speeds and the second segment is the exit queue segment. A car or a truck is assumed to be a point without length. The class-specific pi parameter is used to transform the effect of truck into passenger car equivalents, so the exit flow of cars and trucks can be calculated according to the exit capacity of a bottleneck. The analytic expression of multiple vehicle type dynamic marginal cost function is deduced under congested and uncongested conditions. Then a heuristic algorithm is presented in solving multiple vehicle type dynamic queues, tolls under system optimum and user equilibrium conditions. The numerical example illustrates the simplicity and applicability of the proposed approach.

  10. Surgical approach in patients with hyperparathyroidism in multiple endocrine neoplasia type 1: total versus partial parathyroidectomy

    Directory of Open Access Journals (Sweden)

    Francesco Tonelli

    2012-01-01

    Full Text Available Usually, primary hyperparathyroidism is the first endocrinopathy to be diagnosed in patients with multiple endocrine neoplasia type 1, and is also the most common one. The timing of the surgery and strategy in multiple endocrine neoplasia type 1/hyperparathyroidism are still under debate. The aims of surgery are to: 1 correct hypercalcemia, thus preventing persistent or recurrent hyperparathyroidism; 2 avoid persistent hypoparathyroidism; and 3 facilitate the surgical treatment of possible recurrences. Currently, two types of surgical approach are indicated: 1 subtotal parathyroidectomy with removal of at least 3-3 K glands; and 2 total parathyroidectomy with grafting of autologous parathyroid tissue. Transcervical thymectomy must be performed with both of these procedures. Unsuccessful surgical treatment of hyperparathyroidism is more frequently observed in multiple endocrine neoplasia type 1 than in sporadic hyperparathyroidism. The recurrence rate is strongly influenced by: 1 the lack of a pre-operative multiple endocrine neoplasia type 1 diagnosis; 2 the surgeon's experience; 3 the timing of surgery; 4 the possibility of performing intra-operative confirmation (histologic examination, rapid parathyroid hormone assay of the curative potential of the surgical procedure; and, 5 the surgical strategy. Persistent hyperparathyroidism seems to be more frequent after subtotal parathyroidectomy than after total parathyroidectomy with autologous graft of parathyroid tissue. Conversely, recurrent hyperparathyroidism has a similar frequency in the two surgical strategies. To plan further operations, it is very helpful to know all the available data about previous surgery and to undertake accurate identification of the site of recurrence.

  11. An analysis of the discrete-option multiple-choice item type

    Directory of Open Access Journals (Sweden)

    Neal M. Kingston

    2012-03-01

    Full Text Available The discrete-option multiple-choice (DOMC item type was developed to curtail cheating and reduce the impact of testwiseness, but to date there has been only one published study of its statistical characteristics, and that was based on a relatively small sample. This study was implemented to investigate the psychometric properties of the DOMC item type and systematically compare it with the traditional multiple-choice (MC item type. Test forms written to measure high school-level mathematics were administered to 802 students from two large universities. Results showed that across all forms, MC items were consistently easier than DOMC items. Item discriminations between DOMC and MC items varied randomly, with neither performing consistently better than the other. Results of a confirmatory factor analysis was consistent with a single factor across the two item types.

  12. Novel multiple endocrine neoplasia type 1 variations in patients with sporadic primary hyperparathyroidism

    Directory of Open Access Journals (Sweden)

    S Birla

    2016-01-01

    Full Text Available Background and Objectives: Primary hyperparathyroidism (PHPT can occur either as a sporadic case or in association with syndromes such as multiple endocrine neoplasia. Multiple endocrine neoplasia type 1 (MEN1 is a rare autosomal-dominant disease resulting from mutations in MEN1 gene encoding a 621 amino acid long tumor suppressor protein “menin.” We report here the results of MEN1 screening in 31 patients diagnosed with sporadic PHPT. Materials and Methods: Diagnosis of sporadic PHPT was made when blood urea and serum creatinine were normal, serum parathyroid hormone was high, and parathyroid enlargement could be localized on ultrasound and/or parathyroid scan. A total of 31 patients and 50 healthy volunteers were recruited for molecular analysis after taking informed consent. Results: Major symptoms at presentation were bone pain, fatigue, muscle weakness, and renal stones. Molecular genetic analysis revealed the presence of two novel intronic variations, c. 913-79T>A and c. 784-129T>A which by human splicing finder are predicted to cause potential alteration of splicing by either activating an intronic cryptic acceptor site or converting a conserved exonic splicing silencer sequence to an exonic splicing enhancer site. Apart from these, two reported polymorphisms rs144677807 and rs669976 were seen only in patients and none of the controls. Other reported polymorphisms rs2071313 and rs654440 were identified both in controls and patients. Conclusions: This is the first study of MEN1 gene screening in sporadic PHPT in India reporting on the clinical and genetic findings, wherein two novel intronic variations c. 913-79T>A and c. 784-129T>A were identified showing their possible role in disease causation.

  13. Littelmann patterns and Weyl group multiple Dirichlet series of type D

    CERN Document Server

    Chinta, Gautam

    2009-01-01

    We formulate a conjecture for the local parts of Weyl group multiple Dirichlet series attached to root systems of type D. Our conjecture is analogous to the description of the local parts of type A series given by Brubaker, Bump, Friedberg, and Hoffstein in terms of Gelfand--Tsetlin patterns. Our conjecture is given in terms of patterns for irreducible representations of even orthogonal Lie algebras developed by Littelmann.

  14. BH3 mimetics activate multiple pro-autophagic pathways.

    Science.gov (United States)

    Malik, S A; Orhon, I; Morselli, E; Criollo, A; Shen, S; Mariño, G; BenYounes, A; Bénit, P; Rustin, P; Maiuri, M C; Kroemer, G

    2011-09-15

    The BH3 mimetic ABT737 induces autophagy by competitively disrupting the inhibitory interaction between the BH3 domain of Beclin 1 and the anti-apoptotic proteins Bcl-2 and Bcl-X(L), thereby stimulating the Beclin 1-dependent allosteric activation of the pro-autophagic lipid kinase VPS34. Here, we examined whether ABT737 stimulates other pro-autophagic signal-transduction pathways. ABT737 caused the activating phosphorylation of AMP-dependent kinase (AMPK) and of the AMPK substrate acetyl CoA carboxylase, the activating phosphorylation of several subunits of the inhibitor of NF-κB (IκB) kinase (IKK) and the hyperphosphorylation of the IKK substrate IκB, inhibition of the activity of mammalian target of rapamycin (mTOR) and consequent dephosphorylation of the mTOR substrate S6 kinase. In addition, ABT737 treatment dephosphorylates (and hence likewise inhibits) p53, glycogen synthase kinase-3 and Akt. All these effects were shared by ABT737 and another structurally unrelated BH3 mimetic, HA14-1. Functional experiments revealed that pharmacological or genetic inhibition of IKK, Sirtuin and the p53-depleting ubiquitin ligase MDM2 prevented ABT737-induced autophagy. These results point to unexpected and pleiotropic pro-autophagic effects of BH3 mimetics involving the modulation of multiple signalling pathways.

  15. Predicting and preventing the future: actively managing multiple sclerosis.

    LENUS (Irish Health Repository)

    Hutchinson, Michael

    2012-02-01

    Relapsing-remitting multiple sclerosis (MS) has a highly variable clinical course but a number of demographic, clinical and MRI features can guide the clinician in the assessment of disease activity and likely disability outcome. It is also clear that the inflammatory activity in the first five years of relapsing-remitting MS results in the neurodegenerative changes seen in secondary progressive MS 10-15 years later. While conventional first-line disease modifying therapy has an effect on relapses, about one third of patients have a suboptimal response to treatment. With the advent of highly active second-line therapies with their evident marked suppression of inflammation, the clinician now has the tools to manage the course of relapsing-remitting MS more effectively. The development of treatment optimisation recommendations based on the clinical response to first-line therapies can guide the neurologist in more active management of the early course of relapsing-remitting MS, with the aim of preventing both acute inflammatory axonal injury and the neurodegenerative process which leads to secondary progressive MS.

  16. A rare presentation of multiple endocrine neoplasia (MEN type 2A syndrome

    Directory of Open Access Journals (Sweden)

    Elroy Patrick Weledji

    2016-02-01

    Full Text Available Peptic ulcer disease may be a manifestation of symptomatic primary hyperparathyroidism. A case of an intractable complicated peptic ulcer disease secondary to hypercalcaemia from multiple endocrine neoplasia type 2A is presented. Hypercalcaemia should always be excluded as a cause of recurrent, or complicated peptic ulcer disease.

  17. Error Types in the Approximate System of Arab Students of English: A Multiple Classificatory Taxonomy

    Science.gov (United States)

    Btoosh, Mousa A.

    2011-01-01

    This study aims at providing a comprehensive account of the types of errors produced by Arab students of English as a second language based on a multiple classificatory taxonomy developed for this purpose. The corpus providing the database for the study consists of three parts: (i) short tape-recorded interviews, (ii) translated sentences and…

  18. Post-surgical follow-up of primary hyperparathyroidism associated with multiple endocrine neoplasia type 1

    Directory of Open Access Journals (Sweden)

    Flavia L. Coutinho

    2012-01-01

    Full Text Available The bone mineral density increments in patients with sporadic primary hyperparathyroidism after parathyroidectomy have been studied by several investigators, but few have investigated this topic in primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Further, as far as we know, only two studies have consistently evaluated bone mineral density values after parathyroidectomy in cases of primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Here we revised the impact of parathyroidectomy (particularly total parathyroidectomy followed by autologous parathyroid implant into the forearm on bone mineral density values in patients with primary hyperparathyroidism associated with multiple endocrine neoplasia type 1. Significant increases in bone mineral density in the lumbar spine and femoral neck values were found, although no short-term (15 months improvement in bone mineral density at the proximal third of the distal radius was observed. Additionally, short-term and medium-term calcium and parathyroid hormone values after parathyroidectomy in patients with primary hyperparathyroidism associated with multiple endocrine neoplasia type 1 are discussed. In most cases, this surgical approach was able to restore normal calcium/parathyroid hormone levels and ultimately lead to discontinuation of calcium and calcitriol supplementation.

  19. Tumor-Specific Multiple Stimuli-Activated Dendrimeric Nanoassemblies with Metabolic Blockade Surmount Chemotherapy Resistance.

    Science.gov (United States)

    Li, Yachao; Xu, Xianghui; Zhang, Xiao; Li, Yunkun; Zhang, Zhijun; Gu, Zhongwei

    2017-01-24

    Chemotherapy resistance remains a serious impediment to successful antitumor therapy around the world. However, existing chemotherapeutic approaches are difficult to cope with the notorious multidrug resistance in clinical treatment. Herein, we developed tumor-specific multiple stimuli-activated dendrimeric nanoassemblies with a metabolic blockade to completely combat both physiological barriers and cellular factors of multidrug resistance. With a sophisticated molecular and supramolecular engineering, this type of tumor-specific multiple stimuli-activated nanoassembly based on dendrimeric prodrugs can hierarchically break through the sequential physiological barriers of drug resistance, including stealthy dendritic PEGylated corona to optimize blood transportation, robust nanostructures for efficient tumor passive targeting and accumulation, enzyme-activated tumor microenvironment targeted to deepen tumor penetration and facilitate cellular uptake, cytoplasmic redox-sensitive disintegration for sufficient release of encapsulated agents, and lysosome acid-triggered nucleus delivery of antitumor drugs. In the meantime, we proposed a versatile tactic of a tumor-specific metabolism blockade for provoking several pathways (ATP restriction, apoptotic activation, and anti-apoptotic inhibition) to restrain multiple cellular factors of drug resistance. The highly efficient antitumor activity to drug-resistant MCF-7R tumor in vitro and in vivo supports this design and strongly defeats both physiological barriers and cellular factors of chemotherapy resistance. This work sets up an innovative dendrimeric nanosystem to surmount multidrug resistance, contributing to the development of a comprehensive nanoparticulate strategy for future clinical applications.

  20. Multiple types of human papillomavirus in cervical samples in women in Campo Grande, MS, Brazil

    Directory of Open Access Journals (Sweden)

    Inês Aparecida Tozetti

    2006-10-01

    Full Text Available We analyzed 87 cervical samples from Campo Grande, Mato Grosso do Sul, with a PGMY/GP+ nested PCR system. Positive samples were typed using E7 type-specific primer pairs for HPV 6/11, 16, 18, 45 and 66. Eighteen samples (22% were infected with HPV6/11, 18 samples (22% with HPV66, 13 samples (15.9% with HPV45, 8 samples (9.8% with HPV18 and 7 samples (8.5% with HPV16. Seventeen samples (20.7% were infected by two HPV types, and five samples (6.1% by three HPV types. We conclude that infection with multiple types is present at a high frequency in our population and that there is a relation between some types and cytological finds.

  1. Blockade of nonhormonal fibroblast growth factors by FP-1039 inhibits growth of multiple types of cancer.

    Science.gov (United States)

    Harding, Thomas C; Long, Li; Palencia, Servando; Zhang, Hongbing; Sadra, Ali; Hestir, Kevin; Patil, Namrata; Levin, Anita; Hsu, Amy W; Charych, Deborah; Brennan, Thomas; Zanghi, James; Halenbeck, Robert; Marshall, Shannon A; Qin, Minmin; Doberstein, Stephen K; Hollenbaugh, Diane; Kavanaugh, W Michael; Williams, Lewis T; Baker, Kevin P

    2013-03-27

    The fibroblast growth factor (FGF) pathway promotes tumor growth and angiogenesis in many solid tumors. Although there has long been interest in FGF pathway inhibitors, development has been complicated: An effective FGF inhibitor must block the activity of multiple mitogenic FGF ligands but must spare the metabolic hormone FGFs (FGF-19, FGF-21, and FGF-23) to avoid unacceptable toxicity. To achieve these design requirements, we engineered a soluble FGF receptor 1 Fc fusion protein, FP-1039. FP-1039 binds tightly to all of the mitogenic FGF ligands, inhibits FGF-stimulated cell proliferation in vitro, blocks FGF- and vascular endothelial growth factor (VEGF)-induced angiogenesis in vivo, and inhibits in vivo growth of a broad range of tumor types. FP-1039 antitumor response is positively correlated with RNA levels of FGF2, FGF18, FGFR1c, FGFR3c, and ETV4; models with genetic aberrations in the FGF pathway, including FGFR1-amplified lung cancer and FGFR2-mutated endometrial cancer, are particularly sensitive to FP-1039-mediated tumor inhibition. FP-1039 does not appreciably bind the hormonal FGFs, because these ligands require a cell surface co-receptor, klotho or β-klotho, for high-affinity binding and signaling. Serum calcium and phosphate levels, which are regulated by FGF-23, are not altered by administration of FP-1039. By selectively blocking nonhormonal FGFs, FP-1039 treatment confers antitumor efficacy without the toxicities associated with other FGF pathway inhibitors.

  2. Activation of endogenous neural stem cells for multiple sclerosis therapy

    Directory of Open Access Journals (Sweden)

    Iliana eMichailidou

    2015-01-01

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory disorder of the central nervous system, leading to severe neurological deficits. Current MS treatment regimens, consist of immunomodulatory agents aiming to reduce the rate of relapses. However, these agents are usually insufficient to treat chronic neurological disability.A promising perspective for future therapy of MS is the regeneration of lesions with replacement of the damaged oligodendrocytes or neurons. Therapies targeting to the enhancement of endogenous remyelination, aim to promote the activation of either the parenchymal oligodendrocyte progenitor cells or the subventricular zone-derived neural stem cells (NSCs. Less studied but highly potent, is the strategy of neuronal regeneration with endogenous NSCs that although being linked to numerous limitations, is anticipated to ameliorate cognitive disability in MS. Focusing on the forebrain, this review highlights the role of NSCs in the regeneration of MS lesions.

  3. Mutant p53: multiple mechanisms define biologic activity in cancer

    Directory of Open Access Journals (Sweden)

    Michael Paul Kim

    2015-11-01

    Full Text Available The functional importance of p53 as a tumor suppressor gene is evident through its pervasiveness in cancer biology. The p53 gene is the most commonly altered gene in human cancer; however, not all genetic alterations are biologically equivalent. The majority of p53 alterations involve missense mutations that result in the production of mutant p53 proteins. Such mutant p53 proteins lack normal p53 function and may acquire novel functions, often with deleterious effects. Here, we review characterized mechanisms of mutant p53 gain of function in multiple model systems. In addition, we review mutant p53 addiction as emerging evidence suggests that tumors may depend on sustained mutant p53 activity for continued growth. We also discuss the role of p53 in stromal elements and their contribution to tumor initiation and progression. Lastly, current genetic mouse models of mutant p53 are reviewed and their limitations discussed.

  4. Twist1 activity thresholds define multiple functions in limb development.

    Science.gov (United States)

    Krawchuk, Dayana; Weiner, Shoshana J; Chen, You-Tzung; Lu, Benson C; Costantini, Frank; Behringer, Richard R; Laufer, Ed

    2010-11-01

    The basic helix-loop-helix transcription factor Twist1 is essential for normal limb development. Twist1(-/-) embryos die at midgestation. However, studies on early limb buds found that Twist1(-/-) mutant limb mesenchyme has an impaired response to FGF signaling from the apical ectodermal ridge, which disrupts the feedback loop between the mesenchyme and AER, and reduces and shifts anteriorly Shh expression in the zone of polarizing activity. We have combined Twist1 null, hypomorph and conditional alleles to generate a Twist1 allelic series that survives to birth. As Twist1 activity is reduced, limb skeletal defects progress from preaxial polydactyly to girdle reduction combined with hypoplasia, aplasia or mirror symmetry of all limb segments. With reduced Twist1 activity there is striking and progressive upregulation of ectopic Shh expression in the anterior of the limb, combined with an anterior shift in the posterior Shh domain, which is expressed at normal intensity, and loss of the posterior AER. Consequently limb outgrowth is initially impaired, before an ectopic anterior Shh domain expands the AER, promoting additional growth and repatterning. Reducing the dosage of FGF targets of the Etv gene family, which are known repressors of Shh expression in anterior limb mesenchyme, strongly enhances the anterior skeletal phenotype. Conversely this and other phenotypes are suppressed by reducing the dosage of the Twist1 antagonist Hand2. Our data support a model whereby multiple Twist1 activity thresholds contribute to early limb bud patterning, and suggest how particular combinations of skeletal defects result from differing amounts of Twist1 activity.

  5. Oscillations and multiple steady states in active membrane transport models.

    Science.gov (United States)

    Vieira, F M; Bisch, P M

    1994-01-01

    The dynamic behavior of some non-linear extensions of the six-state alternating access model for active membrane transport is investigated. We use stoichio-metric network analysis to study the stability of steady states. The bifurcation analysis has been done through standard numerical methods. For the usual six-state model we have proved that there is only one steady state, which is globally asymptotically stable. When we added an autocatalytic step we found self-oscillations. For the competition between a monomer cycle and a dimer cycle, with steps of dimer formation, we have also found self-oscillations. We have also studied models involving the formation of a complex with other molecules. The addition of two steps for formation of a complex of the monomer with another molecule does not alter either the number or the stability of steady states of the basic six-state model. The model which combines the formation of a complex with an autocatalytic step shows both self-oscillations and multiple steady states. The results lead us to conclude that oscillations could be produced by active membrane transport systems if the transport cycle contains a sufficiently large number of steps (six in the present case) and is coupled to at least one autocatalytic reaction,. Oscillations are also predicted when the monomer cycle is coupled to a dimer cycle. In fact, the autocatalytic reaction can be seen as a simplification of the model involving competition between monomer and dimer cycles, which seems to be a more realistic description of biological systems. A self-regulation mechanism of the pumps, related to the multiple stationary states, is expected only for a combined effect of autocatalysis and formation of complexes with other molecules. Within the six-state model this model also leads to oscillation.

  6. Multiple scales analysis and travelling wave solutions for KdV type nonlinear evolution equations

    Science.gov (United States)

    Ayhan, Burcu; Ozer, M. Naci; Bekir, Ahmet

    2017-01-01

    Nonlinear evolution equations are the mathematical models of problems that arise in many field of science. These equations has become an important field of study in applied mathematics in recent years. We apply exact solution methods and multiple scale method which is known as a perturbation method to nonlinear evolution equations. Using exact solution methods we get travelling wave solutions expressed by hyperbolic functions, trigonometric functions and rational functions. Also we derive Nonlinear Schrödinger (NLS) type equations from Korteweg-de Vries (KdV) type nonlinear evolution equations and we get approximate solutions for KdV type equations using multiple scale method. The proposed methods are direct and effective and can be used for many nonlinear evolution equations. It is shown that these methods provide a powerful mathematical tool to solve nonlinear evolution equations in mathematical physics.

  7. Multiple mechanisms of action of pyridoxine in primary hyperoxaluria type 1.

    Science.gov (United States)

    Fargue, Sonia; Rumsby, Gill; Danpure, Christopher J

    2013-10-01

    Primary hyperoxaluria type 1 (PH1) is a rare hereditary calcium oxalate kidney stone disease caused by a deficiency of the liver-specific pyridoxal-phosphate-dependent peroxisomal enzyme alanine:glyoxylate aminotransferase (AGT). About one third of patients are responsive to pharmacological doses of pyridoxine (vitamin B6), but its mechanism of action is unknown. Using stably transformed Chinese Hamster Ovary (CHO) cells expressing various normal and mutant forms of AGT, we have shown that pyridoxine increases the net expression, catalytic activity and peroxisomal import of the most common mistargeted mutant form of AGT (i.e. Gly170Arg on the background of the polymorphic minor allele). These multiple effects explain for the first time the action of pyridoxine in the most common group of responsive patients. Partial effects of pyridoxine were also observed for two other common AGT mutants on the minor allele (i.e. Phe152Ile and Ile244Thr) but not for the minor allele mutant AGT containing a Gly41Arg replacement. These findings demonstrate that pyridoxine, which is metabolised to pyridoxal phosphate, the essential cofactor of AGT, achieves its effects both as a prosthetic group (increasing enzyme catalytic activity) and a chemical chaperone (increasing peroxisome targeting and net expression). This new understanding should aid the development of pharmacological treatments that attempt to enhance efficacy of pyridoxine in PH1, as well as encouraging a re-evaluation of the extent of pyridoxine responsiveness in PH1, as more patients than previously thought might benefit from such treatment.

  8. Multiple, Unilateral Lisch Nodules in the Absence of Other Manifestations of Neurofibromatosis Type 1

    Directory of Open Access Journals (Sweden)

    E. G. Adams

    2011-01-01

    Full Text Available Lisch nodules associated with Neurofibromatosis Type 1 (NF1 are usually multiple and bilateral in nature. Here, we report a 21-year-old healthy, Caucasian female who was diagnosed with multiple, unilateral Lisch nodules during routine eye examination. A thorough history and physical examination revealed no other signs of NF1. We diagnosed the rare occurrence of numerous, unilateral Lisch nodules in the absence of additional features of NF1 in our patient and provide a discussion concerning the differential diagnosis of Lisch nodules as well as the potential genetic explanation of this finding.

  9. Multiple dermoid sinuses of type Vb and IIIb on the head of a Saint Bernard dog

    Science.gov (United States)

    2013-01-01

    Dermoid sinus, a congenital malformation of neural tube development, has been reported in humans and several animal species including dogs. It is typically found in the dorsal midline and commonly occurs in the Rhodesian Ridgeback breed. A case of multiple dermoid sinuses in the fronto-occipital region is described. An 11-month-old, intact female Saint Bernard dog was presented with a 2 day history of discharge from a large irregular subcutaneous mass in the fronto-occipital region. The dog was otherwise healthy. The dog had two circular skin lesions (approximately 4 × 4 and 4 × 2 cm diameter) surrounded by multiple irregular elevated masses. The masses had multiple small openings on the skin surface with tufts of hair protruding from the apertures. The masses were surgically removed, and the diagnosis of multiple dermoid sinuses was confirmed by histological examination. Histopathological examination showed multiple, variably sized, spherical to tubular cysts expanding the dermis and subcutis. Cysts were filled with hair shafts and lamellar keratin and were lined by a stratified squamous epithelium. Sebaceous and apocrine gland adnexal structures were also observed. To the best of our knowledge, this is the first reported case of multiple dermoid sinuses of two different types in the head of a Saint Bernard dog. PMID:24006855

  10. Multiplicative point process as a model of trading activity

    Science.gov (United States)

    Gontis, V.; Kaulakys, B.

    2004-11-01

    Signals consisting of a sequence of pulses show that inherent origin of the 1/ f noise is a Brownian fluctuation of the average interevent time between subsequent pulses of the pulse sequence. In this paper, we generalize the model of interevent time to reproduce a variety of self-affine time series exhibiting power spectral density S( f) scaling as a power of the frequency f. Furthermore, we analyze the relation between the power-law correlations and the origin of the power-law probability distribution of the signal intensity. We introduce a stochastic multiplicative model for the time intervals between point events and analyze the statistical properties of the signal analytically and numerically. Such model system exhibits power-law spectral density S( f)∼1/ fβ for various values of β, including β= {1}/{2}, 1 and {3}/{2}. Explicit expressions for the power spectra in the low-frequency limit and for the distribution density of the interevent time are obtained. The counting statistics of the events is analyzed analytically and numerically, as well. The specific interest of our analysis is related with the financial markets, where long-range correlations of price fluctuations largely depend on the number of transactions. We analyze the spectral density and counting statistics of the number of transactions. The model reproduces spectral properties of the real markets and explains the mechanism of power-law distribution of trading activity. The study provides evidence that the statistical properties of the financial markets are enclosed in the statistics of the time interval between trades. A multiplicative point process serves as a consistent model generating this statistics.

  11. Assessment of Personality Types and Locus of Control in Multiple Sclerosis Patients

    Directory of Open Access Journals (Sweden)

    Sh. Mazaheri

    2008-07-01

    Full Text Available Introduction & Objective: Multiple sclerosis (MS is an autoimmune disease with unknown cause. MS is one of the disabling neurologic diseases in adult especially young range that myelin part of central nervous system (CNS is destructed. The aim of this study was assessment of types A and B personality and internal and external locus of control in multiple sclerosis (MS patients and comparison of the results with control group.Materials & Methods: In a case-control study, 30 patients with MS and 30 normal persons as control group evaluated with neurological examination, Rotter locus of control test and Friedman-Rosenman questionnaire for detection of types A and B personality. We employed to analyze the results.Results: 43 percent and 57 percent of MS patients had internal and external locus of control respectively. 63 percent and 37 percent of MS patients had type A and B personality respectively. 60 percent and 40 percent of control group had internal and external locus of control respectively. 20 percent and 80 percent of control group had type A and B personality respectively. Difference between personality type in two groups was significant (P<0.01.Conclusions: In this study, MS patients had more type A personality in comparison to control group.

  12. Mechanisms for multiple activity modes of VTA dopamine neurons

    Directory of Open Access Journals (Sweden)

    Andrew eOster

    2015-07-01

    Full Text Available Midbrain ventral segmental area (VTA dopaminergic neurons send numerous projections to cortical and sub-cortical areas, and diffusely release dopamine (DA to their targets. DA neurons display a range of activity modes that vary in frequency and degree of burst firing. Importantly, DA neuronal bursting is associated with a significantly greater degree of DA release than an equivalent tonic activity pattern. Here, we introduce a single compartmental, conductance-based computational model for DA cell activity that captures the behavior of DA neuronal dynamics and examine the multiple factors that underlie DA firing modes: the strength of the SK conductance, the amount of drive, and GABA inhibition. Our results suggest that neurons with low SK conductance fire in a fast firing mode, are correlated with burst firing, and require higher levels of applied current before undergoing depolarization block. We go on to consider the role of GABAergic inhibition on an ensemble of dynamical classes of DA neurons and find that strong GABA inhibition suppresses burst firing. Our studies suggest differences in the distribution of the SK conductance and GABA inhibition levels may indicate subclasses of DA neurons within the VTA. We further identify, that by considering alternate potassium dynamics, the dynamics display burst patterns that terminate via depolarization block, akin to those observed in vivo in VTA DA neurons and in substantia nigra pars compacta DA cell preparations under apamin application. In addition, we consider the generation of transient burst firing events that are NMDA-initiated or elicited by a sudden decrease of GABA inhibition, that is, disinhibition.

  13. Increased microglial catalase activity in multiple sclerosis grey matter.

    Science.gov (United States)

    Gray, Elizabeth; Kemp, Kevin; Hares, Kelly; Redondo, Julianna; Rice, Claire; Scolding, Neil; Wilkins, Alastair

    2014-04-22

    Chronic demyelination, on-going inflammation, axonal loss and grey matter neuronal injury are likely pathological processes that contribute to disease progression in multiple sclerosis (MS). Although the precise contribution of each process and their aetiological substrates is not fully known, recent evidence has implicated oxidative damage as a major cause of tissue injury in MS. The degree of tissue injury caused by oxidative molecules, such as reactive oxygen species (ROS), is balanced by endogenous anti-oxidant enzymes which detoxify ROS. Understanding endogenous mechanisms which protect the brain against oxidative injury in MS is important, since enhancing anti-oxidant responses is a major therapeutic strategy for preventing irreversible tissue injury in the disease. Our aims were to determine expression and activity levels of the hydrogen peroxide-reducing enzyme catalase in MS grey matter (GM). In MS GM, a catalase enzyme activity was elevated compared to control GM. We measured catalase protein expression by immune dot-blotting and catalase mRNA by a real-time polymerase chain reaction (RT-PCR). Protein analysis studies showed a strong positive correlation between catalase and microglial marker IBA-1 in MS GM. In addition, calibration of catalase mRNA level with reference to the microglial-specific transcript AIF-1 revealed an increase in this transcript in MS. This was reflected by the extent of HLA-DR immunolabeling in MS GM which was significantly elevated compared to control GM. Collectively, these observations provide evidence that microglial catalase activity is elevated in MS grey matter and may be an important endogenous anti-oxidant defence mechanism in MS.

  14. Dynamical Behaviors of Multiple Equilibria in Competitive Neural Networks With Discontinuous Nonmonotonic Piecewise Linear Activation Functions.

    Science.gov (United States)

    Nie, Xiaobing; Zheng, Wei Xing

    2016-03-01

    This paper addresses the problem of coexistence and dynamical behaviors of multiple equilibria for competitive neural networks. First, a general class of discontinuous nonmonotonic piecewise linear activation functions is introduced for competitive neural networks. Then based on the fixed point theorem and theory of strict diagonal dominance matrix, it is shown that under some conditions, such n -neuron competitive neural networks can have 5(n) equilibria, among which 3(n) equilibria are locally stable and the others are unstable. More importantly, it is revealed that the neural networks with the discontinuous activation functions introduced in this paper can have both more total equilibria and locally stable equilibria than the ones with other activation functions, such as the continuous Mexican-hat-type activation function and discontinuous two-level activation function. Furthermore, the 3(n) locally stable equilibria given in this paper are located in not only saturated regions, but also unsaturated regions, which is different from the existing results on multistability of neural networks with multiple level activation functions. A simulation example is provided to illustrate and validate the theoretical findings.

  15. Continued Kinematic and Photometric Investigations of Hierarchical Solar-type Multiple Star Systems

    Science.gov (United States)

    Roberts, Lewis C., Jr.; Tokovinin, Andrei; Mason, Brian D.; Marinan, Anne D.

    2017-03-01

    We observed 15 of the solar-type binaries within 67 pc of the Sun previously observed by the Robo-AO system in the visible, with the PHARO near-infrared camera and the PALM-3000 adaptive optics system on the 5 m Hale telescope. The physical status of the binaries is confirmed through common proper motion and detection of orbital motion. In the process, we detected a new candidate companion to HIP 95309. We also resolved the primary of HIP 110626 into a close binary, making that system a triple. These detections increase the completeness of the multiplicity survey of the solar-type stars within 67 pc of the Sun. Combining our observations of HIP 103455 with archival astrometric measurements and RV measurements, we are able to compute the first orbit of HIP 103455, showing that the binary has a 68 year period. We place the components on a color–magnitude diagram and discuss each multiple system individually.

  16. Contamination event detection using multiple types of conventional water quality sensors in source water.

    Science.gov (United States)

    Liu, Shuming; Che, Han; Smith, Kate; Chen, Lei

    2014-08-01

    Early warning systems are often used to detect deliberate and accidental contamination events in a water system. Conventional methods normally detect a contamination event by comparing the predicted and observed water quality values from one sensor. This paper proposes a new method for event detection by exploring the correlative relationships between multiple types of conventional water quality sensors. The performance of the proposed method was evaluated using data from contaminant injection experiments in a laboratory. Results from these experiments demonstrated the correlative responses of multiple types of sensors. It was observed that the proposed method could detect a contamination event 9 minutes after the introduction of lead nitrate solution with a concentration of 0.01 mg L(-1). The proposed method employs three parameters. Their impact on the detection performance was also analyzed. The initial analysis showed that the correlative response is contaminant-specific, which implies that it can be utilized not only for contamination detection, but also for contaminant identification.

  17. MRI findings in patients with multiple lacunar infarcts manifesting hyperactive-type delirium

    Energy Technology Data Exchange (ETDEWEB)

    Arahata, Yutaka; Motegi, Yoshimasa; Furuse, Masahiro (Nakatsugawa Municipal General Hospital, Gifu (Japan)); Watanabe, Masaki; Takahashi, Akira

    1994-04-01

    MRI studies were carried out on 69 patients with multiple lacunar infarcts: 32 had hyperactive-type delirium and the other 37 were non-delirious controls. Between the two groups, there were no statistically significant differences in mean age and sex distribution. In the corona radiata and basal ganglia, the number of infarcts did not differ between the two groups. However, the extent of thalamic infarcts and periventricular hyperintensity (PVH), the maximal width of the third ventricle and Evans' ratio among the delirious patients were significantly larger than those in the controls. In conclusion, thalamic lesions and diffuse advanced PVH may have an intimate correlation in the development of hyperactive-type delirium in patients with multiple lacunar infarcts. (author).

  18. Psychotic-affective symptoms and multiple system atrophy expand phenotypes of spinocerebellar ataxia type 2

    OpenAIRE

    Chen, Kai-Hsiang; Lin, Chin-Hsien; Wu, Ruey-Meei

    2012-01-01

    Spinocerebellar ataxia type 2 (SCA2) is a progressive neurodegenerative disorder, characterised by ataxic gait, slow saccades and peripheral neuropathy. Levodopa-responsive parkinsonism could be a clinical phenotype of SCA2, especially those of Chinese origin. In addition to these motor symptoms, SCA2 has been associated with depression and cognitive dysfunction, with only rare reports of psychosis. The authors report the presence of severe psychosis, major depression and multiple system atro...

  19. Management of multiple type Ⅱ endoleaks detected by duplex ultrasound after endovascular abdominal aneurysm repair

    Institute of Scientific and Technical Information of China (English)

    GUO Da-qiao; LI Wei-miao; JIANG Jun-hao; SHI Zhen-yu; WANG Yu-qi; FU Wei-guo

    2012-01-01

    We reported a case of multiple type Ⅱ endoleaks detected by duplex ultrasound after endovascular abdominal aneurysm repair.The patient was undergoing warfarin therapy.Duplex ultrasound was applied as the sole surveillance method during follow-up and provided the concerned information for reintervention.The endoleaks were successfully repaired by coil embolization of the collaterals from the internal iliac artery feeding the fourth lumbar artery.

  20. Multiple positive solutions for Kirchhoff type problems involving concave and convex nonlinearities in R^3

    Directory of Open Access Journals (Sweden)

    Xiaofei Cao

    2016-11-01

    Full Text Available In this article, we consider the multiplicity of positive solutions for a class of Kirchhoff type problems with concave and convex nonlinearities. Under appropriate assumptions, we prove that the problem has at least two positive solutions, moreover, one of which is a positive ground state solution. Our approach is mainly based on the Nehari manifold, Ekeland variational principle and the theory of Lagrange multipliers.

  1. Periodic Solutions for Duffing Type p-Laplacian Equation with Multiple Constant Delays

    Directory of Open Access Journals (Sweden)

    Hong Zhang

    2012-01-01

    Full Text Available Using inequality techniques and coincidence degree theory, new results are provided concerning the existence and uniqueness of periodic solutions for the Duffing type p-Laplacian equation with multiple constant delays of the form (φp(x′(t′+Cx′(t+g0(t,x(t+∑k=1ngk(t,x(t-τk=e(t. Moreover, an example is provided to illustrate the effectiveness of the results in this paper.

  2. Multiple endocrine neoplasia type 2 (Sipple's syndrome): clinical and cytogenetic analysis of a kindred.

    OpenAIRE

    Zatterale, A.; Stabile, M; Nunziata, V; Di Giovanni, G.; Vecchione, R; Ventruto, V

    1984-01-01

    This report describes the clinical and cytogenetic analysis of a kindred with multiple endocrine neoplasia type 2 (MEN-2 or Sipple's syndrome) in two generations. Medullary thyroid carcinoma was present in five members either as a large or as an occult tumour. Phaeochromocytoma was demonstrated in one severely hypertensive relative and urine vanillylmandelic acid (VMA) was increased in one normotensive member. Serum parathormone (PTH) was normal in all but one normocalcaemic patient of this f...

  3. Classic type epithelioid sarcoma mimicking multiple droplet-like abscesses in the lower leg

    Energy Technology Data Exchange (ETDEWEB)

    Park, Eun Hae; Lee, Young Han; Hahn, Seok; Kim, Sang kyum; Suh, Jin Suck [Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2015-06-15

    Epithelioid sarcoma is an uncommon, slow-growing soft tissue tumor that usually arises in the distal part of an upper extremity, predominantly occurring in young adults. Classic-type epithelioid sarcomas appear to be less aggressive and have a better prognosis. In magnetic resonance imaging, epithelioid sarcoma usually appears as a subcutaneous mass or ulcer with cutaneous erosion. Here, we report a classic-type epithelioid sarcoma in a 68-year-old male without an apparent mass, presenting with only numerous small disseminated droplet-like ring-enhancing nodules mimicking abscesses, and multiple metastases.

  4. A Case of Multiple System Atrophy-Cerebellar Type Preceded by Dementia

    Directory of Open Access Journals (Sweden)

    Eun Hye Jang

    2012-10-01

    Full Text Available Multiple system atrophy (MSA is a sporadic, adult-onset disease characterized by progressive degeneration of nervous systems including cerebellar, pyramidal, extrapyramidal, and autonomic system. Although a few recent studies reported that cognitive impairments could occur in patients with MSA, prominent dementia with progressive decline is not a typical clinical manifestation of MSA. In particular, dementia with MSA-cerebellar type is very rare. We have experienced a patient with 2-year history of severe cognitive impairment, who was finally diagnosed as MSA-cerebellar type.

  5. Effect of disease duration on personality type in multiple sclerosis patients and healthy individual

    Directory of Open Access Journals (Sweden)

    Sahar Vesal

    2016-01-01

    Full Text Available Background: Multiple sclerosis may have profound emotional consequences. The relation between psychological and physical factors could lead patients toward unforeseen disease. This study focuses on multiple sclerosis (MS disease duration on personality type A and B in relation to individuals' behaviors. Materials and Methods: This descriptive-analytical study was conducted in Isfahan Alzahra hospital in 2013. Three hundred MS patients and 100 healthy individuals were determined. The distributed questionnaires related to MS patients and considering the descriptive statistics such as demographic variables. Data were analyzed by SPSS software (version 18 based on Chi-square test and independent T-test. Results: Disease duration varied between 1 to 38 years: 30% (1-4 years, 38% (5-10 years, 20% (10-20 years, and 12% (more than 20 years. Significant relationship was observed between disease duration and tendency to type A (higher stress. This relation was positive and significant in Relapsing Remitting MS patients; but negative correlation was seen in Secondary Progressive MS patients. These patients tended to type B (lower stress when disease duration increased. Conclusions: Individuals with disease duration of one year and less than one year tend to type A personality, while patients with increment of disease duration have tendency to type B.

  6. 3D Filament Network Segmentation with Multiple Active Contours

    Science.gov (United States)

    Xu, Ting; Vavylonis, Dimitrios; Huang, Xiaolei

    2014-03-01

    Fluorescence microscopy is frequently used to study two and three dimensional network structures formed by cytoskeletal polymer fibers such as actin filaments and microtubules. While these cytoskeletal structures are often dilute enough to allow imaging of individual filaments or bundles of them, quantitative analysis of these images is challenging. To facilitate quantitative, reproducible and objective analysis of the image data, we developed a semi-automated method to extract actin networks and retrieve their topology in 3D. Our method uses multiple Stretching Open Active Contours (SOACs) that are automatically initialized at image intensity ridges and then evolve along the centerlines of filaments in the network. SOACs can merge, stop at junctions, and reconfigure with others to allow smooth crossing at junctions of filaments. The proposed approach is generally applicable to images of curvilinear networks with low SNR. We demonstrate its potential by extracting the centerlines of synthetic meshwork images, actin networks in 2D TIRF Microscopy images, and 3D actin cable meshworks of live fission yeast cells imaged by spinning disk confocal microscopy.

  7. Estimation of the Performance of Multiple Active Neutron Interrogation Signatures for Detecting Shielded HEU

    Energy Technology Data Exchange (ETDEWEB)

    David L. Chichester; Scott J. Thompson; Scott M. Watson; James T. Johnson; Edward H. Seabury

    2012-10-01

    A comprehensive modeling study has been carried out to evaluate the utility of multiple active neutron interrogation signatures for detecting shielded highly enriched uranium (HEU). The modeling effort focused on varying HEU masses from 1 kg to 20 kg; varying types of shields including wood, steel, cement, polyethylene, and borated polyethylene; varying depths of the HEU in the shields, and varying engineered shields immediately surrounding the HEU including steel, tungsten, and cadmium. Neutron and gamma-ray signatures were the focus of the study and false negative detection probabilities versus measurement time were used as a performance metric. To facilitate comparisons among different approaches an automated method was developed to generate receiver operating characteristic (ROC) curves for different sets of model variables for multiple background count rate conditions. This paper summarizes results or the analysis, including laboratory benchmark comparisons between simulations and experiments. The important impact engineered shields can play towards degrading detectability and methods for mitigating this will be discussed.

  8. Children with profound intellectual and multiple disabilities : the effects of functional movement activities

    NARCIS (Netherlands)

    van der Putten, A; Vlaskamp, C; Reynders, K; Nakken, H

    2005-01-01

    Objective: To determine the effect of functional movement activities within the MOVE ( Mobility Opportunities Via Education) curriculum on the independence of children with profound intellectual and multiple disabilities. Subjects: Forty-four children with profound intellectual and multiple disabili

  9. Differences between spinocerebellar ataxias and multiple system atrophy-cerebellar type on proton magnetic resonance spectroscopy.

    Directory of Open Access Journals (Sweden)

    Jiing-Feng Lirng

    Full Text Available PURPOSE: A broad spectrum of diseases can manifest cerebellar ataxia. In this study, we investigated whether proton magnetic resonance spectroscopy (MRS may help differentiate spinocerebellar ataxias (SCA from multiple systemic atrophy- cerebellar type (MSA-C. MATERIAL AND METHODS: This prospective study recruited 156 patients with ataxia, including spinocerebellar ataxia (SCA types 1, 2, 3, 6 and 17 (N = 94 and MSA-C (N = 62, and 44 healthy controls. Single voxel proton MRS in the cerebellar hemispheres and vermis were measured. The differences were evaluated using nonparametric statistic tests. RESULTS: When compared with healthy controls, the cerebellar and vermis NAA/Cr and NAA/Cho were lower in all patients(p<0.002. The Cho/Cr was lower in SCA2 and MSA-C (p<0.0005. The NAA/Cr and Cho/Cr were lower in MSA-C or SCA2 comparing with SCA3 or SCA6. The MRS features of SCA1 were in between (p<0.018. The cerebellar NAA/Cho was lower in SCA2 than SCA1, SCA3 or SCA6 (p<0.04. The cerebellar NAA/Cho in MSA-C was lower than SCA3 (p<0.0005. In the early stages of diseases (SARA score<10, significant lower NAA/Cr and NAA/Cho in SCA2, SCA3, SCA6 or MSA-C were observed comparing with healthy controls (p<0.017. The Cho/Cr was lower in MSA-C or SCA2 (p<0.0005. Patients with MSA-C and SCA2 had lower NAA/Cr and Cho/Cr than SCA3 or SCA6 (p<0.016. CONCLUSION: By using MRS, significantly lower NAA/Cr, Cho/Cr and NAA/Cho in the cerebellar hemispheres and vermis were found in patients with ataxia (SCAs and MSA-C. Rapid neuronal degeneration and impairment of membrane activities were observed more often in patients with MSA-C than those with SCA, even in early stages. MRS could also help distinguish between SCA2 and other subtypes of SCAs. MRS ratios may be of use as biomarkers in early stages of disease and should be further assessed in a longitudinal study.

  10. Complex heterogeneous tissue constructs containing multiple cell types prepared by inkjet printing technology.

    Science.gov (United States)

    Xu, Tao; Zhao, Weixin; Zhu, Jian-Ming; Albanna, Mohammad Z; Yoo, James J; Atala, Anthony

    2013-01-01

    This study was designed to develop a versatile method for fabricating complex and heterogeneous three-dimensional (3D) tissue constructs using simultaneous ink-jetting of multiple cell types. Human amniotic fluid-derived stem cells (hAFSCs), canine smooth muscle cells (dSMCs), and bovine aortic endothelial cells (bECs), were separately mixed with ionic cross-linker calcium chloride (CaCl(2)), loaded into separate ink cartridges and printed using a modified thermal inkjet printer. The three cell types were delivered layer-by-layer to pre-determined locations in a sodium alginate-collagen composite located in a chamber under the printer. The reaction between CaCl(2) and sodium alginate resulted in a rapid formation of a solid composite gel and the printed cells were anchored in designated areas within the gel. The printing process was repeated for several cycles leading to a complex 3D multi-cell hybrid construct. The biological functions of the 3D printed constructs were evaluated in vitro and in vivo. Each of the printed cell types maintained their viability and normal proliferation rates, phenotypic expression, and physiological functions within the heterogeneous constructs. The bioprinted constructs were able to survive and mature into functional tissues with adequate vascularization in vivo. These findings demonstrate the feasibility of fabricating complex heterogeneous tissue constructs containing multiple cell types using inkjet printing technology.

  11. Prevalence of Diabetes Type 1 in Patients Suffered From Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Dayer

    2016-04-01

    Full Text Available Background Because IL2RA is considered a predisposing factor in the incidence of both type I diabetes and multiple sclerosis (MS, and considering that both are autoimmune diseases, some studies suggest a correlation between type I diabetes and MS. Objectives The aim of this study was to examine the prevalence of type I diabetes among people with MS. Patients and Methods The study subjects comprised 100 patients with MS from the Khuzestan multiple sclerosis center at rehabilitation school of Jundishapur University of Medical Sciences, whose diagnosis of MS had been confirmed by a specialist, and were not being treated with steroids. Subjects were selected from patients younger than 30 years old. After filling out an application form, 5 mL fasting venous blood and 5 mL after 2 hours were taken. The blood glucose level was measured with a kit (Zist Shimi using the enzymatic method. Results The mean age of the participants was 24.28 years. The rate of type I diabetes was equal to 4% of the total sample, while 18% of all patients had impaired fasting glucose. Conclusions Given the high level of impaired fasting glucose among patients in this study, it is likely that MS provides the basis for the incidence of glucose metabolism disorders. To prove this, further studies with larger sample sizes are required.

  12. Rational Design of Peptide Vaccines Against Multiple Types of Human Papillomavirus.

    Science.gov (United States)

    Dey, Sumanta; De, Antara; Nandy, Ashesh

    2016-01-01

    Human papillomavirus (HPV) occurs in many types, some of which cause cervical, genital, and other cancers. While vaccination is available against the major cancer-causing HPV types, many others are not covered by these preventive measures. Herein, we present a bioinformatics study for the designing of multivalent peptide vaccines against multiple HPV types as an alternative strategy to the virus-like particle vaccines being used now. Our technique of rational design of peptide vaccines is expected to ensure stability of the vaccine against many cycles of mutational changes, elicit immune response, and negate autoimmune possibilities. Using the L1 capsid protein sequences, we identified several peptides for potential vaccine design for HPV 16, 18, 33, 35, 45, and 11 types. Although there are concerns about the epitope-binding affinities for the peptides identified in this process, the technique indicates possibilities of multivalent, adjuvanted, peptide vaccines against a wider range of HPV types, and tailor-made different combinations of the peptides to address frequency variations of types over different population groups as required for prophylaxis and at lower cost than are in use at the present time.

  13. Administrative Judicial Decisions as a Hybrid Argumentative Activity Type

    NARCIS (Netherlands)

    Plug, H.J.

    2016-01-01

    This article focuses on strategic manoeuvring that takes place in Dutch administrative judi- cial decisions. These decisions may be seen as a distinct argumentative activity type. Starting from the char- acteristics that traditionally are per- tinent to this activity type, I will explore how implica

  14. Type IV collagen-degrading enzyme activity in human serum.

    Directory of Open Access Journals (Sweden)

    Hashimoto,Noriaki

    1988-02-01

    Full Text Available Type IV collagen-degrading enzyme activity was detected in human serum. Serum was preincubated with 4-aminophenylmercuric acetate and trypsin to activate the enzyme prior to assay. Type IV collagen, purified from human placentas and radiolabeled with [1-14C] acetic anhydride, was used as the substrate. The enzyme activity was measured at pH 7.5 and inhibited by treatment with ethylenediaminetetraacetic acid or heat. The assay of type IV collagen-degrading enzyme in human serum might be useful for estimating the degradation of type IV collagen.

  15. The relation between the types of multiple intelligences and the training departments of candidate teachers

    Directory of Open Access Journals (Sweden)

    Sibel Gürbüzoğlu Yalmancı

    2011-03-01

    Full Text Available The purpose of this study is to investigate the relation between the types of multiple intelligences of faculty of education students and the training departments of candidate teachers. The sample of this study was composed of 191 candidate teachers still studying in Kafkas University Education Faculty in Undergraduate Programs; class teacher education, social science education, science education and Turkish education programs. In this study one of the survey methods; general survey method was used.“Multiple Intelligences Areas Inventory for Adults” prepared by Ziya Selçuk (2003 was applied to students as data collection instrument. For the analysis of data gathered; one-way ANOVA statistics were used. As the results of the study, it is seen that there is a significant difference between the training departments of candidate teachers and their logical-mathematical, visual-spatial and interpersonal intelligence.

  16. Neurofibromatosis Type 1 Diagnosed in a Child Based on Multiple Juvenile Xanthogranulomas and Juvenile Myelomonocytic Leukemia

    DEFF Research Database (Denmark)

    Jans, Sune R R; Schomerus, Eckhard; Bygum, Anette

    2015-01-01

    An association between juvenile xanthogranuloma (JXG), neurofibromatosis type 1 (NF1), and juvenile myelomonocytic leukemia (JMML) has been described in the literature but has only been documented in approximately 20 cases. We diagnosed a patient with NF1 at 25 months of age, before any cutaneous...... stigmata of this disease had appeared, because we decided to screen for the NF1 gene mutation because of his presentation with multiple JXGs and moderate macrocephaly (2.5 standard deviations) at 9 months of age and JMML diagnosed at 20 months of age. The child is well today after treatment...... with chemotherapy and allogenic bone marrow transplantation. With increased awareness, patients with JXG and NF1 who develop symptoms possibly related to JMML, such as paleness, skin bleeding, cough, unexplained fever, and hepatosplenomegaly, should be further evaluated. We also emphasize that multiple JXG lesions...

  17. Superficial Type of Multiple Basal Cell Carcinomas: Detailed Comparative Study of Its Dermoscopic and Histopathological Findings

    Directory of Open Access Journals (Sweden)

    Akiko Hirofuji

    2011-01-01

    Full Text Available We investigated in detail the dermoscopic and histopathological findings in a case of a superficial type of multiple basal cell carcinomas (BCCs. These multiple lesions (occurring in the chest, neck, and back showed three different findings, respectively. Dermoscopy of the erythematous and brown-colored patch on the anterior chest showed spoke wheel areas, and the histopathological cross-section revealed vertical spoke wheel structures. In the black- and brown-colored patch at the neck, the dermatoscopy showed a maple leaf-like structure, which was in accordance with the strengthening of the histological lateral connection of the lesion. The brown-colored patch of the lateral back histologically showed irregularly enlarged spoke wheel-like areas with peripheral increased melanin pigments, which correlated with the dark black color of dermoscopic maple leaf-like areas. The vertical spoke wheel areas by dermatoscopy revealed a horizontal spoke wheel structure by histopathology.

  18. Multiple-source multiple-harmonic active vibration control of variable section cylindrical structures: A numerical study

    Science.gov (United States)

    Liu, Jinxin; Chen, Xuefeng; Gao, Jiawei; Zhang, Xingwu

    2016-12-01

    Air vehicles, space vehicles and underwater vehicles, the cabins of which can be viewed as variable section cylindrical structures, have multiple rotational vibration sources (e.g., engines, propellers, compressors and motors), making the spectrum of noise multiple-harmonic. The suppression of such noise has been a focus of interests in the field of active vibration control (AVC). In this paper, a multiple-source multiple-harmonic (MSMH) active vibration suppression algorithm with feed-forward structure is proposed based on reference amplitude rectification and conjugate gradient method (CGM). An AVC simulation scheme called finite element model in-loop simulation (FEMILS) is also proposed for rapid algorithm verification. Numerical studies of AVC are conducted on a variable section cylindrical structure based on the proposed MSMH algorithm and FEMILS scheme. It can be seen from the numerical studies that: (1) the proposed MSMH algorithm can individually suppress each component of the multiple-harmonic noise with an unified and improved convergence rate; (2) the FEMILS scheme is convenient and straightforward for multiple-source simulations with an acceptable loop time. Moreover, the simulations have similar procedure to real-life control and can be easily extended to physical model platform.

  19. The VLT-FLAMES Tarantula Survey XXII. Multiplicity properties of the B-type stars

    CERN Document Server

    Dunstall, P R; Sana, H; Evans, C J; Howarth, I D; Simón-Díaz, S; de Mink, S E; Langer, N; Apellániz, J Maíz; Taylor, W D

    2015-01-01

    We investigate the multiplicity properties of 408 B-type stars observed in the 30 Doradus region of the Large Magellanic Cloud with multi-epoch spectroscopy from the VLT-FLAMES Tarantula Survey (VFTS). We use a cross-correlation method to estimate relative radial velocities from the helium and metal absorption lines for each of our targets. Objects with significant radial-velocity variations (and with an amplitude larger than 16 km/s) are classified as spectroscopic binaries. We find an observed spectroscopic binary fraction (defined by periods of 0.1) for the B-type stars, f_B(obs) = 0.25 +/- 0.02, which appears constant across the field of view, except for the two older clusters (Hodge 301 and SL 639). These two clusters have significantly lower fractions of 0.08 +/- 0.08 and 0.10 +/- 0.09, respectively. Using synthetic populations and a model of our observed epochs and their potential biases, we constrain the intrinsic multiplicity properties of the dwarf and giant (i.e. relatively unevolved) B-type stars ...

  20. Nonfunctional Metastatic Parathyroid Carcinoma in the Setting of Multiple Endocrine Neoplasia Type 2A Syndrome

    Directory of Open Access Journals (Sweden)

    María Posada-González

    2014-01-01

    Full Text Available Parathyroid carcinoma is a very rare malignancy. It has been associated with hyperparathyroidism-jaw tumour syndrome, familial isolated primary hyperparathyroidism, and multiple endocrine neoplasia type 1 (MEN-1 and 2A (MEN-2A syndromes. We report a 54-year-old man with a MEN-2A which presents with a nonfunctional metastatic parathyroid carcinoma and a pheochromocytoma in the absence of medullary thyroid carcinoma. Only a few cases of parathyroid carcinoma have been reported in the literature associated with this syndrome.

  1. Asymptotic Stability of Caputo Type Fractional Neutral Dynamical Systems with Multiple Discrete Delays

    Directory of Open Access Journals (Sweden)

    Hai Zhang

    2014-01-01

    Full Text Available We discuss the delay-independent asymptotic stability of Caputo type fractional-order neutral differential systems with multiple discrete delays. Based on the algebraic approach and matrix theory, the sufficient conditions are derived to ensure the asymptotic stability for all time-delay parameters. By applying the stability criteria, one can avoid solving the roots of transcendental equations. The results obtained are computationally flexible and convenient. Moreover, an example is provided to illustrate the effectiveness and applicability of the proposed theoretical results.

  2. Failure to demonstrate human T cell lymphotropic virus type I in multiple sclerosis patients

    DEFF Research Database (Denmark)

    Fugger, L; Morling, N; Ryder, L P;

    1990-01-01

    The polymerase chain reaction (PCR) technique was employed in searching for human T cell lymphotropic virus type I (HTLV-I) gag, env and pol sequences in samples of DNA prepared from two HTLV-I seropositive patients with tropical spastic paraparesis (TSP), the Swedish multiple sclerosis (MS...... and detection probes. In MS patients and healthy individuals, no signals were obtained with gag and env. In occasional experiments, weak signals were seen for the pol segment for a single MS patient and/or healthy individuals, but these signals were not reproducible in subsequent experiments. Thus, the present...

  3. How do different types of physical activity affect mode?

    OpenAIRE

    高橋, 信二; 坂入, 洋右; 吉田, 雄大; 木塚, 朝博

    2012-01-01

    Generally, typical physical activities (e.g. walking and cycling) increase positive affect and decrease negative affect. However, few studies have investigated the effects on mood of activities that are frequently pursued during leisure time (e.g. dynamic stretching and video games). The purpose of the present study was to investigate the influences of different types of physical activity on mood. We selected 16 activities (kendama, active video games ["Wii Sports" tennis, baseball, boxing], ...

  4. Diffusion of Active Particles Subject both to Additive and Multiplicative Noises

    Institute of Scientific and Technical Information of China (English)

    WANG Shao-Hua; YANG Ming; WU Da-Jin

    2011-01-01

    We consider a Langevin equation of active Brownian motion which contains a multiplicative as well as an additive noise term.We study the dependences of the effective diffusion coefficient Deff on both the additive and multiplicative noises.It is found that for fixed small additive noise intensity Deff varies non-monotonously with multiplicative noise intensity, with a minimum at a moderate value of multiplicative noise, and Deff increases monotonously, however, with the multiplicative noise intensity for relatively strong additive noise; for fixed multiplicative noise intensity Deff decreases with growing additive noise intensity until it approaches a constant.An explanation is also given of the different behavior of Deff as additive and multiplicative noises approach infinity,respectively.%@@ We consider a Langevin equation of active Brownian motion which contains a multiplicative as well as an additive noise term.We study the dependences of the effective diffusion coefficient Deff on both the additive and multiplicative noises.It is found that for fixed small additive noise intensity Deff varies non-monotonously with multiplicative noise intensity, with a minimum at a moderate value of multiplicative noise, and Deff increases monotonously, however, with the multiplicative noise intensity for relatively strong additive noise; for fixed multiplicative noise intensity Deff decreases with growing additive noise intensity until it approaches a constant.An explanation is also given of the different behavior of Deff as additive and multiplicative noises approach infinity, respectively.

  5. Laser-Bioplasma Interaction: The Blood Type Transmutation Induced by Multiple Ultrashort Wavelength Laser Beams

    Science.gov (United States)

    Stefan, V. Alexander

    2015-11-01

    The interaction of ultrashort wavelength multi laser beams with the flowing blood thin films leads to the transmutation of the blood types A, B, and AB into O type. This is a novel mechanism of importance for the transfusion medicine. Laser radiation is in resonance with the eigen-frequency modes of the antigen proteins and forces the proteins to parametrically oscillate until they get kicked out from the surface. The stripping away of antigens is done by the scanning-multiple-lasers of a high repetition rate in the blue-purple frequency domain. The guiding-lasers are in the red-green frequency domain. The laser force, (parametric interaction with the antigen eigen-oscillation), upon the antigen protein molecule must exceed its weight. The scanning laser beam is partially reflected as long as the antigen(s) is not eliminated. The process of the protein detachment can last a few minutes. Supported by Nikola Tesla Labs., Stefan University.

  6. Simulations of the Gravitationally Confined Detonation Model of Type Ia Supernovae for Multiple Ignition Points

    Science.gov (United States)

    Jordan, G. C.; Meakin, C. A.; Hearn, N.; Fisher, R. T.; Townsley, D. M.; Lamb, D. Q.; Truran, J. W.

    2009-04-01

    In this paper we present 3D simulations of the gravitationally confined detonation (GCD) model of Type Ia Supernovae with multiple ignition points as initial conditions. These simulations release more energy during the deflagration (subsonic nuclear combustion) phase than previous GCD simulations initiated with a single ignition point. Due to the increased amount of fuel consumed during the deflagration, the star undergoes a more energetic pulsation which at the time of detonation increases the amount of low-density, intermediate-mass-producing material and decreases the amount of high-density, NSE-producing material. This results in the production of approximately 0.7 M⊙ of 56Ni in the explosion, an amount that observations indicate is produced in Type Ia supernovae having typical luminosities.

  7. Diverse intracellular pathogens activate type III interferon expression from peroxisomes.

    Science.gov (United States)

    Odendall, Charlotte; Dixit, Evelyn; Stavru, Fabrizia; Bierne, Helene; Franz, Kate M; Durbin, Ann Fiegen; Boulant, Steeve; Gehrke, Lee; Cossart, Pascale; Kagan, Jonathan C

    2014-08-01

    Type I interferon responses are considered the primary means by which viral infections are controlled in mammals. Despite this view, several pathogens activate antiviral responses in the absence of type I interferons. The mechanisms controlling type I interferon-independent responses are undefined. We found that RIG-I like receptors (RLRs) induce type III interferon expression in a variety of human cell types, and identified factors that differentially regulate expression of type I and type III interferons. We identified peroxisomes as a primary site of initiation of type III interferon expression, and revealed that the process of intestinal epithelial cell differentiation upregulates peroxisome biogenesis and promotes robust type III interferon responses in human cells. These findings highlight the importance of different intracellular organelles in specific innate immune responses.

  8. Impact of RET proto-oncogene analysis on the clinical management of multiple endocrine neoplasia type 2

    Directory of Open Access Journals (Sweden)

    Toledo Sergio Pereira de Almeida

    2006-01-01

    Full Text Available Multiple endocrine neoplasia type 2 (MEN2 is an autosomal dominant disease characterized by the presence of medullary thyroid carcinoma, primary hyperparathyroidism, and pheochromocytoma. Multiple endocrine neoplasia type 2 is still an underdiagnosed, or late-diagnosed condition in many areas of the world. Since 1993, when the first missense RET proto-oncogene (RET mutations were reported in MEN2, up to 46 different RET-causing disease mutations have been described. Since a strong genotype-phenotype correlation exists for MEN2, the detection of RET mutations has produced a major impact in early recognition and treatment of MTC and MEN2. Presently, RET mutation analysis should be performed for all MEN2 cases and their at-risk familial relatives. Further, prophylactic total thyroidectomy is indicated in all cases harboring activating gametic RET mutations. In most RET mutation carriers, prophylactic total thyroidectomy is indicated at ages as early as a few months to 4 years of age, promoting longer survival and improvement of quality of life or even definitive cure. We discuss the large impact of RET proto-oncogene analysis on the clinical management of MEN2 and the role of early RET molecular DNA diagnosis in providing clinicians and surgeons with valuable information that enables them to indicate early total thyroidectomy.

  9. Activation of endogenous neural stem cells for multiple sclerosis therapy

    NARCIS (Netherlands)

    Michailidou, Iliana; de Vries, Helga E.; Hol, Elly M.; van Strien, Miriam E.

    2015-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, leading to severe neurological deficits. Current MS treatment regimens, consist of immunomodulatory agents aiming to reduce the rate of relapses. However, these agents are usually insufficient to treat chronic

  10. Activation of endogenous neural stem cells for multiple sclerosis therapy

    NARCIS (Netherlands)

    Michailidou, I.; de Vries, H.E.; Hol, E.M.; van Strien, M.E.

    2014-01-01

    Multiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system, leading to severe neurological deficits. Current MS treatment regimens, consist of immunomodulatory agents aiming to reduce the rate of relapses. However, these agents are usually insufficient to treat chronic

  11. The parietal cortex in sensemaking: the dissociation of multiple types of spatial information.

    Science.gov (United States)

    Sun, Yanlong; Wang, Hongbin

    2013-01-01

    According to the data-frame theory, sensemaking is a macrocognitive process in which people try to make sense of or explain their observations by processing a number of explanatory structures called frames until the observations and frames become congruent. During the sensemaking process, the parietal cortex has been implicated in various cognitive tasks for the functions related to spatial and temporal information processing, mathematical thinking, and spatial attention. In particular, the parietal cortex plays important roles by extracting multiple representations of magnitudes at the early stages of perceptual analysis. By a series of neural network simulations, we demonstrate that the dissociation of different types of spatial information can start early with a rather similar structure (i.e., sensitivity on a common metric), but accurate representations require specific goal-directed top-down controls due to the interference in selective attention. Our results suggest that the roles of the parietal cortex rely on the hierarchical organization of multiple spatial representations and their interactions. The dissociation and interference between different types of spatial information are essentially the result of the competition at different levels of abstraction.

  12. The Contribution of Immune and Glial Cell Types in Experimental Autoimmune Encephalomyelitis and Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Samuel S. Duffy

    2014-01-01

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory disease of the central nervous system characterised by widespread areas of focal demyelination. Its aetiology and pathogenesis remain unclear despite substantial insights gained through studies of animal models, most notably experimental autoimmune encephalomyelitis (EAE. MS is widely believed to be immune-mediated and pathologically attributable to myelin-specific autoreactive CD4+ T cells. In recent years, MS research has expanded beyond its focus on CD4+ T cells to recognise the contributions of multiple immune and glial cell types to the development, progression, and amelioration of the disease. This review summarises evidence of T and B lymphocyte, natural killer cell, macrophage/microglial, astrocytic, and oligodendroglial involvement in both EAE and MS and the intercommunication and influence of each cell subset in the inflammatory process. Despite important advances in the understanding of the involvement of these cell types in MS, many questions still remain regarding the various subsets within each cell population and their exact contribution to different stages of the disease.

  13. Type IV collagen-degrading enzyme activity in human serum.

    OpenAIRE

    Hashimoto, Noriaki; Kobayashi, Michio; Watanabe,Akiharu; Higashi, Toshiro; Tsuji, Takao

    1988-01-01

    Type IV collagen-degrading enzyme activity was detected in human serum. Serum was preincubated with 4-aminophenylmercuric acetate and trypsin to activate the enzyme prior to assay. Type IV collagen, purified from human placentas and radiolabeled with [1-14C] acetic anhydride, was used as the substrate. The enzyme activity was measured at pH 7.5 and inhibited by treatment with ethylenediaminetetraacetic acid or heat. The assay of type IV collagen-degrading enzyme in human serum might be useful...

  14. Efficacy of natalizumab in multiple sclerosis patients with high disease activity: a Danish nationwide study

    DEFF Research Database (Denmark)

    Oturai, A.B.; Koch-Henriksen, N.; Petersen, T.;

    2009-01-01

    INTRODUCTION: Previous studies of natalizumab (Tysabri) in relapsing multiple sclerosis (MS) patients have included patients with moderate disease activity. We studied a patient population with high disease activity. PATIENTS AND METHODS: We analyzed data from 234 consecutive, natalizumab-treated...

  15. Distribution patterns of infection with multiple types of human papillomaviruses and their association with risk factors.

    Directory of Open Access Journals (Sweden)

    Sara Soto-De Leon

    Full Text Available BACKGROUND: Infection with multiple types of human papillomavirus (HPV is one of the main risk factors associated with the development of cervical lesions. In this study, cervical samples collected from 1,810 women with diverse sociocultural backgrounds, who attended to their cervical screening program in different geographical regions of Colombia, were examined for the presence of cervical lesions and HPV by Papanicolau testing and DNA PCR detection, respectively. PRINCIPAL FINDINGS: The negative binomial distribution model used in this study showed differences between the observed and expected values within some risk factor categories analyzed. Particularly in the case of single infection and coinfection with more than 4 HPV types, observed frequencies were smaller than expected, while the number of women infected with 2 to 4 viral types were higher than expected. Data analysis according to a negative binomial regression showed an increase in the risk of acquiring more HPV types in women who were of indigenous ethnicity (+37.8%, while this risk decreased in women who had given birth more than 4 times (-31.1%, or were of mestizo (-24.6% or black (-40.9% ethnicity. CONCLUSIONS: According to a theoretical probability distribution, the observed number of women having either a single infection or more than 4 viral types was smaller than expected, while for those infected with 2-4 HPV types it was larger than expected. Taking into account that this study showed a higher HPV coinfection rate in the indigenous ethnicity, the role of underlying factors should be assessed in detail in future studies.

  16. Distribution Patterns of Infection with Multiple Types of Human Papillomaviruses and Their Association with Risk Factors

    Science.gov (United States)

    Soto-De Leon, Sara; Camargo, Milena; Sanchez, Ricardo; Munoz, Marina; Perez-Prados, Antonio; Purroy, Antonio; Patarroyo, Manuel Elkin; Patarroyo, Manuel Alfonso

    2011-01-01

    Background Infection with multiple types of human papillomavirus (HPV) is one of the main risk factors associated with the development of cervical lesions. In this study, cervical samples collected from 1,810 women with diverse sociocultural backgrounds, who attended to their cervical screening program in different geographical regions of Colombia, were examined for the presence of cervical lesions and HPV by Papanicolau testing and DNA PCR detection, respectively. Principal Findings The negative binomial distribution model used in this study showed differences between the observed and expected values within some risk factor categories analyzed. Particularly in the case of single infection and coinfection with more than 4 HPV types, observed frequencies were smaller than expected, while the number of women infected with 2 to 4 viral types were higher than expected. Data analysis according to a negative binomial regression showed an increase in the risk of acquiring more HPV types in women who were of indigenous ethnicity (+37.8%), while this risk decreased in women who had given birth more than 4 times (−31.1%), or were of mestizo (−24.6%) or black (−40.9%) ethnicity. Conclusions According to a theoretical probability distribution, the observed number of women having either a single infection or more than 4 viral types was smaller than expected, while for those infected with 2–4 HPV types it was larger than expected. Taking into account that this study showed a higher HPV coinfection rate in the indigenous ethnicity, the role of underlying factors should be assessed in detail in future studies. PMID:21379574

  17. Insight into Genotype-Phenotype Associations through eQTL Mapping in Multiple Cell Types in Health and Immune-Mediated Disease.

    Directory of Open Access Journals (Sweden)

    James E Peters

    2016-03-01

    Full Text Available Genome-wide association studies (GWAS have transformed our understanding of the genetics of complex traits such as autoimmune diseases, but how risk variants contribute to pathogenesis remains largely unknown. Identifying genetic variants that affect gene expression (expression quantitative trait loci, or eQTLs is crucial to addressing this. eQTLs vary between tissues and following in vitro cellular activation, but have not been examined in the context of human inflammatory diseases. We performed eQTL mapping in five primary immune cell types from patients with active inflammatory bowel disease (n = 91, anti-neutrophil cytoplasmic antibody-associated vasculitis (n = 46 and healthy controls (n = 43, revealing eQTLs present only in the context of active inflammatory disease. Moreover, we show that following treatment a proportion of these eQTLs disappear. Through joint analysis of expression data from multiple cell types, we reveal that previous estimates of eQTL immune cell-type specificity are likely to have been exaggerated. Finally, by analysing gene expression data from multiple cell types, we find eQTLs not previously identified by database mining at 34 inflammatory bowel disease-associated loci. In summary, this parallel eQTL analysis in multiple leucocyte subsets from patients with active disease provides new insights into the genetic basis of immune-mediated diseases.

  18. Togetherness of the Multiple Diverticulosis of the First Part of the Duodenum with Neurofibromatosis Type I: A Case Report

    Directory of Open Access Journals (Sweden)

    Ozgur Turk

    2014-04-01

    Full Text Available Duedonal diverticulosis is common in clinical practice. Most of duedonal diverticulosis is located at the second part of duodenum; incidence is reported as 67%, incidence of third and forth part is %20. Multiple diverticulosis of the first part of the duodenum is a rare case. There is not any knowledge togetherness of neurofibromatosis type 1 and duedonal diverticulosis. Here we reported incidentally diagnosed multiple diverticulosis of duodenum that is located in the first part in a neurofibromatosis type 1 patient with multiple neurofibromatosis nodules. Neurofibromatosis could affect various organs. Along the digestive system carcinoid tumors and neuroendocrine tumors are more encountered diseases. Endoscopic examinations and abdominal imaging may be useful for the diagnosis of gastrointestinal coexisting disease in neurofibromatosis type 1 . In conclusion neurofibromatosis type 1 could affect multiple systems and it should evaluate carefully.

  19. Multiple endocrine neoplasia phenocopy revealed as a co-occurring neuroendocrine tumor and familial hypocalciuric hypercalcemia type 3

    DEFF Research Database (Denmark)

    Hovden, Silje; Jespersen, Marie Louise; Nissen, Peter H;

    2016-01-01

    Familial hypocalciuric hypercalcemia type 3 should be considered as differential diagnosis in patients with suspected primary hyperparathyroidism and/or suspected multiple neoplasia syndrome, as correct diagnosis will spare the patients for going through multiple futile parathyroidectomies and fo...... and for the worry of being diagnosed with a cancer susceptibility syndrome....

  20. Evaluation of anti-diabetic activity of Glucova Active Tablet on Type I and Type II diabetic model in rats

    Directory of Open Access Journals (Sweden)

    Hardik Soni

    2014-01-01

    Full Text Available Background: Glucova Active Tablet is a proprietary Ayurvedic formulation with ingredients reported for anti-hyperglycemic, anti-hyperlipidemic activity and antioxidant properties. Objective: Evaluation of anti-diabetic activity of Glucova Active Tablet on Type I and Type II diabetic model in rats. Materials and Methods: Experimental Type I diabetes was induced in 24 albino rats with intra-peritoneal injection of streptozotocin (50 mg/kg. Type II diabetes was induced in 18 albino rats by intra-peritoneal injection of streptozotocin (35 mg/kg along with high fat diet. The rats were divided in 5 groups for Type I model and 4 groups for Type II model. Normal control group was kept common for both experimental models. Glucova Active Tablet (108 mg/kg treatment was provided for 28 days twice daily orally. Fasting blood glucose level, serum lipid profile and liver anti-oxidant parameters like superoxide dismutase and reduced glutathione was carried out in both experimental models. Pancreas histopathology was also done. Statistical analysis were done by ′analysis of variance′ test followed by post hoc Tukey′s test, with significant level of P < 0.05.Results and Discussion: Glucova Active Tablet showed significant effect on fasting blood glucose level. It also showed significant alteration in lipid profile and antioxidant parameters. Histopathology study revealed restoration of beta cells in pancreas in Glucova Active Tablet treated group. Conclusion: Finding of this study concludes that Glucova Active Tablet has shown promising anti-diabetic activity in Type I and Type II diabetic rats. It was also found showing good anti-hyperlipidemic activity and anti-oxidant property.

  1. Evaluation of anti-diabetic activity of Glucova Active Tablet on Type I and Type II diabetic model in rats

    Science.gov (United States)

    Soni, Hardik; Patel, Sejal; Patel, Ghanshyam; Paranjape, Archana

    2014-01-01

    Background: Glucova Active Tablet is a proprietary Ayurvedic formulation with ingredients reported for anti-hyperglycemic, anti-hyperlipidemic activity and antioxidant properties. Objective: Evaluation of anti-diabetic activity of Glucova Active Tablet on Type I and Type II diabetic model in rats. Materials and Methods: Experimental Type I diabetes was induced in 24 albino rats with intra-peritoneal injection of streptozotocin (50 mg/kg). Type II diabetes was induced in 18 albino rats by intra-peritoneal injection of streptozotocin (35 mg/kg) along with high fat diet. The rats were divided in 5 groups for Type I model and 4 groups for Type II model. Normal control group was kept common for both experimental models. Glucova Active Tablet (108 mg/kg) treatment was provided for 28 days twice daily orally. Fasting blood glucose level, serum lipid profile and liver anti-oxidant parameters like superoxide dismutase and reduced glutathione was carried out in both experimental models. Pancreas histopathology was also done. Statistical analysis were done by ‘analysis of variance’ test followed by post hoc Tukey's test, with significant level of P < 0.05. Results and Discussion: Glucova Active Tablet showed significant effect on fasting blood glucose level. It also showed significant alteration in lipid profile and antioxidant parameters. Histopathology study revealed restoration of beta cells in pancreas in Glucova Active Tablet treated group. Conclusion: Finding of this study concludes that Glucova Active Tablet has shown promising anti-diabetic activity in Type I and Type II diabetic rats. It was also found showing good anti-hyperlipidemic activity and anti-oxidant property. PMID:24948860

  2. Administrative Judicial Decisions as a Hybrid Argumentative Activity Type

    OpenAIRE

    Plug, H.J.

    2016-01-01

    This article focuses on strategic manoeuvring that takes place in Dutch administrative judi- cial decisions. These decisions may be seen as a distinct argumentative activity type. Starting from the char- acteristics that traditionally are per- tinent to this activity type, I will explore how implications of current discussions on the changing task of the administrative judge may be- come manifest in the judge’s strate- gic manoeuvring by means of the presentation of argumentation and the intr...

  3. Biochemically curative surgery for gastrinoma in multiple endocrine neoplasia type 1 patients

    Institute of Scientific and Technical Information of China (English)

    Masayuki Imamura; Izumi Komoto; Shuichi Ota; Takuya Hiratsuka; Shinji Kosugi; Ryuichiro Doi; Masaaki Awane; Naoya Inoue

    2011-01-01

    AIM: To search for the optimal surgery for gastrinoma and duodenopancreatic neuroendocrine tumors in patients with multiple endocrine neoplasia type 1. METHODS: Sixteen patients with genetically confirmed multiple endocrine neoplasia type 1 (MEN 1) and Zollinger-Ellison syndrome (ZES) underwent resection of both gastrinomas and duodenopancreatic neuroendocrine tumors (NETs) between 1991 and 2009. For localization of gastrinoma, selective arterial secretagogue injection test (SASI test) with secretin or calcium solution was performed as well as somatostatin receptor scintigraphy (SRS) and other imaging methods such as computed tomography (CT) or magnetic resonance imaging (MRI). The modus of surgery for gastrinoma has been changed over time, searching for the optimal surgery: pancreaticoduodenectomy (PD) was first performed guided by localization with the SAST test, then local resection of duodenal gastrinomas with dissection of regional lymph nodes (LR), and recently pancreas-preserving total duodenectomy (PPTD) has been performed for multiple duodenal gastrinomas. RESULTS: Among various types of preoperative localizing methods for gastrinoma, the SASI test was the most useful method. Imaging methods such as SRS or CT made it essentially impossible to differentiate functioning gastrinoma among various kinds of NETs. However, recent imaging methods including SRS or CT were useful for detecting both distant metastases and ectopic NETs; therefore they are indispensable for staging of NETs. Biochemical cure of gastrinoma was achieved in 14 of 16 patients (87.5%); that is, 100% in 3 patients who underwent PD, 100% in 6 patients who underwent LR (although in 2 patients (33.3%) second LR was performed for recurrence of duodenal gastrinoma), and 71.4% in 7 patients who underwent PPTD. Pancreatic NETs more than 1 cm in diameter were resected either by distal pancreatectomy or enucleations, and no hepatic metastases have developed postoperatively. Pathological study of the

  4. Stochastic simulation and spatial estimation with multiple data types using artificial neural networks

    Science.gov (United States)

    Besaw, Lance E.; Rizzo, Donna M.

    2007-11-01

    A novel data-driven artificial neural network (ANN) that quantitatively combines large numbers of multiple types of soft data is presented for performing stochastic simulation and/or spatial estimation. A counterpropagation ANN is extended with a radial basis function to estimate parameter fields that reproduce the spatial structure exhibited in autocorrelated parameters. Applications involve using three geophysical properties measured on a slab of Berea sandstone and the delineation of landfill leachate at a site in the Netherlands using electrical formation conductivity as our primary variable and six types of secondary data (e.g., hydrochemistry, archaea, and bacteria). The ANN estimation fields are statistically similar to geostatistical methods (indicator simulation and cokriging) and reference fields (when available). The method is a nonparametric clustering/classification algorithm that can assimilate significant amounts of disparate data types with both continuous and categorical responses without the computational burden associated with the construction of positive definite covariance and cross-covariance matrices. The combination of simplicity and computational speed makes the method ideally suited for environmental subsurface characterization and other Earth science applications with spatially autocorrelated variables.

  5. Membrane-type photonic integration of InGaN/GaN multiple-quantum-well diodes and waveguide

    Science.gov (United States)

    Gao, Xumin; Bai, Dan; Cai, Wei; Xu, Yin; Yuan, Jialei; Yang, Yongchao; Zhu, Guixia; Cao, Xun; Zhu, Hongbo; Wang, Yongjin

    2017-02-01

    We report here a membrane-type integration of InGaN/GaN multiple-quantum-well diodes (MQWDs) with a waveguide to build a highly integrated photonic system to perform functionalities on a GaN-on-silicon platform. Suspended MQWDs can be used as either for light-emitting diode (LED) or photodiode. In the fabricated photonic system, part of the LED emission is coupled into a suspended waveguide, and the guided light laterally propagates along the waveguide and is finally sensed by the photodiode. The photonic system can detect the in-plane guided light and the external incident light simultaneously. Planar optical communication experimentally demonstrates that the proof-of-concept monolithic photonic integration system can achieve the in-plane visible light communication. This work paves the way towards novel active electro-optical sensing systems and planar optical communication in the visible range.

  6. Methylseleninic acid potentiates multiple types of cancer cells to ABT-737-induced apoptosis by targeting Mcl-1 and Bad

    DEFF Research Database (Denmark)

    Yin, Shutao; Dong, Yinhui; Li, Jinghua

    2012-01-01

    ABT-737, a novel small molecule inhibitor of Bcl-2 family proteins, holds great promise to complement current cancer therapies. However many types of solid cancer cells are resistant to ABT-737. One practical approach to improve its therapeutic efficacy is to combine with the agents that can...... overcome such resistance to restore the sensitivity. In the present study, a second-generation selenium compound methylseleninic acid (MSeA) synergistically sensitized MDA-MB-231 human breast cancer cells, HT-29 human colon cancer cells and DU145 human prostate cancer cells to apoptosis induction by ABT......-737, as evidenced by greater than additive enhancement of Annexin V/FITC positive (apoptotic) cells and activation of multiple caspases and PARP cleavage. Mechanistic investigation demonstrated that MSeA significantly decreased basal Mcl-1 expression and ABT-737-induced Mcl-1 expression. Knocking down...

  7. Evaluation of frequency spectrum and main oscillation modes of box type multiple cross sections spans

    Directory of Open Access Journals (Sweden)

    Sokolov Oleg Leonidovich

    2014-05-01

    Full Text Available From the viewpoint of mechanics the box span of trestle bridges is non-diaphragm prismatic shell of multiple cross section of average length. Though many problems of static analysis of such structures have been solved, the development of analytical methods of calculating non-diaphragm box type structures on the vibration is an urgent task. The presented method for analysis of free vibration of non-diaphragm spans of box trestle bridges of multiple cross sections is based on the variation theory of prismatic shells of average length by V.Z. Vlasov. In this method the discrete-continuum design scheme, in which the mass of the structure is reduced to its nodal lines, is used. Equations of free vibration are variation equations and represent the work of internal and external forces in the possible displacements. The possible displacements are determined by the static approximation. The order frequency equation, obtained by solving the equation system of free vibration, coincides with the number of the vertical walls of the box span. For a split design scheme span the frequency equation is algebraic, and its components are calculated in analytical formulas. The method is illustrated by free vibrations of non-diaphragm box spans with four cross sections. As a result, the solution frequency spectrum and modes of vibration were defined. The advantage of the presented method of calculation is that the components of the frequency equation are calculated in analytical formulas. This method helps to study free vibration non-diaphragm box spans of multiple cross sections depending on changes in the design parameters. Application of this method will reduce the time and improve the design quality, and also monitor the results of structures analysis prepared with the help of computer complex.

  8. A Case Report of Multiple Endocrine Neoplasia Type IIa Associated with Cushing Syndrome

    Directory of Open Access Journals (Sweden)

    Sh. Borzouei

    2013-10-01

    Full Text Available Introduction: Multiple endocrine neoplasia type IIa (MEN IIa is an autosomal dominant syn-drome characterized bypheochromocytoma ,medullary thyroid carcinoma and hyperparathy-roidism. Pheochromocytoma approximately occurs in 50% of patients with MEN IIa. This tumor has the capacity to produce ACTH ectopically and becomes manifest like Cushing syndrome,although it is very rare. Case Report: We report a 26-year-old woman patient with severe muscle weakness, skin le-sions in extremity, hypertension, new onset diabetes and in the laboratory data hypokalemia, metabolic alkalosis, high serum level of cortisol, metanephrine, normetanephrine, calcitonin and bilateral adrenal mass in computed tomography as the first clinical manifestations of an ACTH-secreting pheochromocytoma. Conclusion: In the patients with hypertension, new onset diabetes and hypokalemia Cushing syndrome and pheochromocytoma should always be ruled out. (Sci J Hamadan Univ Med Sci 2013; 20 (3:260-265

  9. Fine-scaling mapping of the gene responsible for multiple endocrine neoplasia type I (MEN1)

    Energy Technology Data Exchange (ETDEWEB)

    Fujimori, Minoru; Nakamura, Yusuke (Cancer Institute, Tokyo (Japan)); Wells, S.A. (Washington University School of Medicine, St. Louis (United States))

    1992-02-01

    The authors have constructed a high-resolution genetic linkage map in the vicinity of the gene responsible for multiple endocrine neoplasia type 1 (MEN1). The mutation causing this disease, inherited as an autosomal dominant, predisposes carriers to development of neoplastic tumors in the parathyroid, the endocrine pancreas, and the anterior lobe of the pituitary. The 12 markers on the genetic linkage map reported here span nearly 20 cM, and linkage analysis of MEN1 pedigrees has placed the MEN1 locus within the 8-cM region between D11S480 and D11S546. The markers on this map will be useful for prenatal or presymptomatic diagnosis of individuals in families that segregate a mutant allele of the MEN1 gene.

  10. An improved early detection method of type-2 diabetes mellitus using multiple classifier system

    KAUST Repository

    Zhu, Jia

    2015-01-01

    The specific causes of complex diseases such as Type-2 Diabetes Mellitus (T2DM) have not yet been identified. Nevertheless, many medical science researchers believe that complex diseases are caused by a combination of genetic, environmental, and lifestyle factors. Detection of such diseases becomes an issue because it is not free from false presumptions and is accompanied by unpredictable effects. Given the greatly increased amount of data gathered in medical databases, data mining has been used widely in recent years to detect and improve the diagnosis of complex diseases. However, past research showed that no single classifier can be considered optimal for all problems. Therefore, in this paper, we focus on employing multiple classifier systems to improve the accuracy of detection for complex diseases, such as T2DM. We proposed a dynamic weighted voting scheme called multiple factors weighted combination for classifiers\\' decision combination. This method considers not only the local and global accuracy but also the diversity among classifiers and localized generalization error of each classifier. We evaluated our method on two real T2DM data sets and other medical data sets. The favorable results indicated that our proposed method significantly outperforms individual classifiers and other fusion methods.

  11. Multiple carcinoids in the duodenum, pancreas and stomach accompanied with type A gastritis: A case report

    Institute of Scientific and Technical Information of China (English)

    Takeo Bamba; Shin-ichi Kosugi; Tatsuo Kanda; Toshihiro Tsubono; Yasuo Sakai; Nobuyuki Musha; Noriko Ishihara; Katsuyoshi Hatakeyama

    2007-01-01

    We report a case of multiple duodenal, pancreatic, and gastric carcinoids. A 67-year old woman was admitted to our hospital for treatment of a duodenal carcinoid.Laboratory tests revealed that the patient was associated with macrocytic anemia and hypergastrinemia, and type A gastritis was shown by gastrofiberscopy.During surgery, another tumor was incidentally found in the head of the pancreas. The tumors in the duodenum and pancreas were completely excised by pancreatoduodenectomy and immunohistologically diagnosed as gastrin-and serotonin-producing carcinoids,respectively. Pathological examination revealed that in addition to the grossly found carcinoids, there were subclinical carcinoids, one of which was an endocrine cell micronest, located in the stomach and duodenum.The tumors in the duodenum, pancreas, and stomach showed different characteristics from one another morphologically and immunochemically. Although no definitive evidence has been obtained, some sort of genetic anomaly may have been involved in this case,and hypergastrinemia due to duodenal gastrinoma may induce multiple gastric carcinoids.

  12. [Multiple endocrine neoplasia type 1 (MEN 1): clinical, biochemical and molecular diagnosis and treatment of the associated disturbances].

    Science.gov (United States)

    Hoff, Ana Oliveira; Hauache, Omar Magid

    2005-10-01

    Multiple endocrine neoplasia (MEN) syndromes include types 1 (MEN 1) and 2 (MEN 2), von Hippel-Lindau syndrome, neurofibromatosis type 1 and Carney complex. These are complex genetic syndromes caused by activation or inactivation of different types of genes known to be involved in the regulation of cell proliferation. In this review we will discuss the clinical manifestations and management of the MEN 1 syndrome as well as the genetic screening of potential MEN 1 gene carriers. MEN 1 is a hereditary syndrome, transmitted in an autosomic dominant fashion and caused by an inactivating mutation of the MEN 1 gene, characterized by the development of primary hyperparathyroidism, islet cell tumors and pituitary adenomas. In addition, these patients can present with cutaneous manifestations such as angiofibromas and collagenomas, and can develop other neoplastic manifestations including carcinoids, thyroid tumors, adrenal adenomas, lipomas, pheochromocytomas and meningiomas. The MEN 1 gene encodes a peptide which is a tumor suppressor gene called menin. Several studies have demonstrated its importance in regulation of cell proliferation and have confirmed its role in the pathogenesis of the MEN 1 syndrome. The discovery of the MEN 1 gene and the genetic analysis of MEN 1 patients have resulted in earlier diagnosis and treatment of asymptomatic carriers which can potentially result in a longer survival of these patients. Further investigation of the function and signaling pathways of the menin protein will hopefully offer therapeutic alternatives to patients with malignant progression of MEN 1-related tumors and also result in improved survival.

  13. Angiogenic activity of sesamin through the activation of multiple signal pathways

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Byung-Hee [Vascular System Research Center and Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon (Korea, Republic of); Division of Food Biotechnology, School of Biotechnology, Kangwon National University, Chuncheon (Korea, Republic of); Lee, Jung Joon [Center for Molecular Cancer Research, Korea Research Institute of Bioscience and Biotechnology, Daejeon (Korea, Republic of); Kim, Jong-Dai [Division of Food Biotechnology, School of Biotechnology, Kangwon National University, Chuncheon (Korea, Republic of); Jeoung, Dooil; Lee, Hansoo [Division of Life Sciences, Kangwon National University, Chuncheon (Korea, Republic of); Choe, Jongseon; Ha, Kwon-Soo [Vascular System Research Center and Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon (Korea, Republic of); Kwon, Young-Geun [Department of Biochemistry, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Kim, Young-Myeong, E-mail: ymkim@kangwon.ac.kr [Vascular System Research Center and Department of Molecular and Cellular Biochemistry, School of Medicine, Kangwon National University, Chuncheon (Korea, Republic of)

    2010-01-01

    The natural product sesamin has been known to act as a potent antioxidant and prevent endothelial dysfunction. We here found that sesamin increased in vitro angiogenic processes, such as endothelial cell proliferation, migration, and tube formation, as well as neovascularization in an animal model. This compound elicited the activation of multiple angiogenic signal modulators, such as ERK, Akt, endothelial nitric oxide synthase (eNOS), NO production, FAK, and p38 MAPK, but not Src. The MEK inhibitor PD98059 and the PI3K inhibitor Wortmannin specifically inhibited sesamin-induced activation of the ERK and Akt/eNOS pathways. These inhibitors reduced angiogenic events, with high specificity for MEK/ERK-dependent cell proliferation and migration and PI3K/Akt-mediated tube formation. Moreover, inhibition of p38 MAPK effectively inhibited sesamin-induced cell migration. The angiogenic activity of sesamin was not associated with VEGF expression. Furthermore, this compound did not induce vascular permeability and upregulated ICAM-1 and VCAM-1 expression, which are hallmarks of vascular inflammation. These results suggest that sesamin stimulates angiogenesis in vitro and in vivo through the activation of MEK/ERK-, PI3K/Akt/eNOS-, p125{sup FAK}-, and p38 MAPK-dependent pathways, without increasing vascular inflammation, and may be used for treating ischemic diseases and tissue regeneration.

  14. Multilocus sequence typing of genital Chlamydia trachomatis in Norway reveals multiple new sequence types and a large genetic diversity.

    Directory of Open Access Journals (Sweden)

    Kirsten Gravningen

    Full Text Available BACKGROUND: The Chlamydia trachomatis incidence rate in Finnmark, the most northern and sparsely populated county in Norway, has been twice the national average. This population based cross-sectional study among Finnmark high school students had the following aims: i to examine distribution of multilocus sequence types (STs of C. trachomatis in a previously unmapped area, ii to compare chlamydia genetic diversity in Finnmark with that of two urban regions, and iii to compare discriminatory capacity of multilocus sequence typing (MLST with conventional ompA sequencing in a large number of chlamydia specimens. METHODOLOGY: ompA sequencing and a high-resolution MLST system based on PCR amplification and DNA sequencing of five highly variable genetic regions were used. Eighty chlamydia specimens from adolescents aged 15-20 years in Finnmark were collected in five high schools (n = 60 and from routine clinical samples in the laboratory (n = 20. These were compared to routine clinical samples from adolescents in Tromsø (n = 80 and Trondheim (n = 88, capitals of North and Central Norway, respectively. PRINCIPAL FINDINGS: ompA sequencing detected 11 genotypes in 248 specimens from all three areas. MLST displayed 50 STs providing a five-fold higher resolution. Two-thirds of all STs were novel. The common ompA E/Bour genotype comprised 46% and resolved into 24 different STs. MLST identified the Swedish new variant of C. trachomatis not discriminated by ompA sequencing. Simpson's discriminatory index (D was 0.93 for MLST, while a corrected D(c was 0.97. There were no statistically significant differences in ST genetic diversity between geographic areas. Finnmark had an atypical genovar distribution with G being predominant. This was mainly due to expansion of specific STs of which the novel ST161 was unique for Finnmark. CONCLUSIONS/SIGNIFICANCE: MLST revealed multiple new STs and a larger genetic diversity in comparison to ompA sequencing

  15. Method of Multiple Scales and Travelling Wave Solutions for (2+1)-Dimensional KdV Type Nonlinear Evolution Equations

    Science.gov (United States)

    Ayhan, Burcu; Özer, M. Naci; Bekir, Ahmet

    2016-08-01

    In this article, we applied the method of multiple scales for Korteweg-de Vries (KdV) type equations and we derived nonlinear Schrödinger (NLS) type equations. So we get a relation between KdV type equations and NLS type equations. In addition, exact solutions were found for KdV type equations. The ( G'} over G )-expansion methods and the ( {G'} over G, {1 over G}} )-expansion methods were proposed to establish new exact solutions for KdV type differential equations. We obtained periodic and hyperbolic function solutions for these equations. These methods are very effective for getting travelling wave solutions of nonlinear evolution equations (NEEs).

  16. The VLT-FLAMES Tarantula Survey VIII. Multiplicity properties of the O-type star population

    CERN Document Server

    Sana, H; de Mink, S E; Dunstall, P R; Evans, C J; Henault-Brunet, V; Apellaniz, J Maiz; Ramirez-Agudelo, O H; Taylor, W D; Walborn, N R; Clark, J S; Crowther, P A; Herrero, A; Gieles, M; Langer, N; Lennon, D J; Vink, J S

    2012-01-01

    Aims. We analyze the multiplicity properties of the massive O-type star population. With 360 O-type stars, this is the largest homogeneous sample of massive stars analyzed to date. Methods. We use multi-epoch spectroscopy and variability analysis to identify spectroscopic binaries. We also use a Monte-Carlo method to correct for observational biases. Results. We observe a spectroscopic binary fraction of 0.35\\pm0.03, which corresponds to the fraction of objects displaying statistically significant radial velocity variations with an amplitude of at least 20km/s. We compute the intrinsic binary fraction to be 0.51\\pm0.04. We adopt power-laws to describe the intrinsic period and mass-ratio distributions: f_P ~ (log P)^\\pi\\ (with 0.15 7.8', i.e. approx117 pc) and among the O9.7 I/II objects are however significantly lower than expected from statistical fluctuations. Conclusions. Using simple evolutionary considerations, we estimate that over 50% of the current O star population in 30 Dor will exchange mass with ...

  17. Clinical utility of C-terminal telopeptide of type 1 collagen in multiple myeloma.

    Science.gov (United States)

    Ting, Kay R; Brady, Jennifer J; Hameed, Abdul; Le, Giao; Meiller, Justine; Verburgh, Estelle; Bayers, Christopher; Benjamin, Dalia; Anderson, Kenneth C; Richardson, Paul G; Dowling, Paul; Clynes, Martin; Fitzgibbon, Maria C; O'Gorman, Peter

    2016-04-01

    Myeloma bone disease (MBD) is a major cause of morbidity in multiple myeloma (MM). We investigated bone turnover markers (BTM) as relapse predictors and biomarkers for monitoring MBD. We measured C-terminal telopeptide of type I collagen (CTX-1), and Procollagen type 1 N Propeptide (P1NP) in 86 MM patients and 26 controls. CTX-1 was higher in newly diagnosed patients compared to control, remission and relapse (P < 0·05), and decreased following treatment. In the setting of relapse, a CTX-1 rise greater than the calculated least significant change (LSC) was observed in 26% of patients 3-6 months prior to relapse (P = 0·007), and in 60·8% up to 3 months before relapse (P = 0·015). Statistically significant changes in CTX-1 levels were also observed in patients who were with and without bisphosphonate therapy at the time of relapse. In patients with normal renal function, mean CTX-1 level was highest in the newly diagnosed group (0·771 ± 0·400 μg/l), and lowest in the remission group (0·099 ± 0·070 μg/l) (P < 0·0001). P1NP levels were not statistically different across the patient groups. We conclude that CTX-1, measured on an automated hospital laboratory platform, has a role in routine treatment monitoring and predicting relapse of MBD, even in patients on bisphosphonates.

  18. Creatine kinase activity in patients with diabetes mellitus type I and type II.

    Science.gov (United States)

    Jevrić-Causević, Adlija; Malenica, Maja; Dujić, Tanja

    2006-08-01

    Diabetes mellitus can be looked upon as an array of diseases, all of which exhibit common symptoms. While pathogenesis of IDDM (insulin dependant diabetes mellitus) is well understood, the same is not true for diabetes mellitus type II. In the latter case, relative contribution of the two factors (insulin resistance or decreased insulin secretion) varies individually, being highly increased in peripheral tissues and strictly dependant on insulin for glucose uptake. Moreover, in patients with diabetes mellitus type II, disbalance at the level of regulation of glucose metabolism as well as lipid metabolism has been noted in skeletal muscles. It is normal to assume that in this type of diabetes, these changes are reflected at the level of total activity of enzyme creatine kinase. This experimental work was performed on a group of 80 regular patients of Sarajevo General Hospital. Forty of those patients were classified as patients with diabetes type I and forty as patients with diabetes type II. Each group of patients was carefully chosen and constituted of equal number of males and females. The same was applied for adequate controls. Concentration of glucose was determined for each patient with GOD method, while activity of creatine kinase was determined with CK-NAC activated kit. Statistical analysis of the results was performed with SPSS software for Windows. Obtained results point out highly expressed differences in enzyme activity between two populations examined. Changes in enzyme activity are more expressed in patients with diabetes type II. Positive correlation between concentration of glucose and serum activity of the enzyme is seen in both categories of diabetic patients which is not the case for the patients in control group. At the same time, correlation between age and type of diabetes does exist . This is not followed at the level of enzyme activity or concentration of glucose.

  19. Tyrosine kinase BMX phosphorylates phosphotyrosine-primed motif mediating the activation of multiple receptor tyrosine kinases.

    Science.gov (United States)

    Chen, Sen; Jiang, Xinnong; Gewinner, Christina A; Asara, John M; Simon, Nicholas I; Cai, Changmeng; Cantley, Lewis C; Balk, Steven P

    2013-05-28

    The nonreceptor tyrosine kinase BMX (bone marrow tyrosine kinase gene on chromosome X) is abundant in various cell types and activated downstream of phosphatidylinositol-3 kinase (PI3K) and the kinase Src, but its substrates are unknown. Positional scanning peptide library screening revealed a marked preference for a priming phosphorylated tyrosine (pY) in the -1 position, indicating that BMX substrates may include multiple tyrosine kinases that are fully activated by pYpY sites in the kinase domain. BMX phosphorylated focal adhesion kinase (FAK) at Tyr⁵⁷⁷ subsequent to its Src-mediated phosphorylation at Tyr⁵⁷⁶. Loss of BMX by RNA interference or by genetic deletion in mouse embryonic fibroblasts (MEFs) markedly impaired FAK activity. Phosphorylation of the insulin receptor in the kinase domain at Tyr¹¹⁸⁹ and Tyr¹¹⁹⁰, as well as Tyr¹¹⁸⁵, and downstream phosphorylation of the kinase AKT at Thr³⁰⁸ were similarly impaired by BMX deficiency. However, insulin-induced phosphorylation of AKT at Ser⁴⁷³ was not impaired in Bmx knockout MEFs or liver tissue from Bmx knockout mice, which also showed increased insulin-stimulated glucose uptake, possibly because of decreased abundance of the phosphatase PHLPP (PH domain leucine-rich repeat protein phosphatase). Thus, by identifying the pYpY motif as a substrate for BMX, our findings suggest that BMX functions as a central regulator among multiple signaling pathways mediated by tyrosine kinases.

  20. Multiple nucleophilic elbows leading to multiple active sites in a single module esterase from Sorangium cellulosum

    DEFF Research Database (Denmark)

    Udatha, D.B.R.K. Gupta; Madsen, Karina Marie; Panagiotou, Gianni;

    2015-01-01

    The catalytic residues in carbohydrate esterase enzyme families constitute a highly conserved triad: serine, histidine and aspartic acid. This catalytic triad is generally located in a very sharp turn of the protein backbone structure, called the nucleophilic elbow and identified by the consensus...... sequence GXSXG. An esterase from Sorangium cellulosum Soce56 that contains five nucleophilic elbows was cloned and expressed in Escherichia coli and the function of each nucleophilic elbowed site was characterized. In order to elucidate the function of each nucleophilic elbow, site directed mutagenesis...... was used to generate variants with deactivated nucleophilic elbows and the functional promiscuity was analyzed. In silico analysis together with enzymological characterization interestingly showed that each nucleophilic elbow formed a local active site with varied substrate specificities and affinities...

  1. Multiple splicing types of OsRIX4, an RAD21 homolog in rice (Oryza sativa L.)

    Institute of Scientific and Technical Information of China (English)

    DONG HaiTao; LI DeBao; GUO XiaoQin; PEI YanXi; DAI ChengEn; FANG YongQi; TU QiChao; ZHUANG JieYun; ZHAO Dong; ZHENG KangLe

    2007-01-01

    The present paper describes multiple splicing types of OsRIX4, an RAD21 homolog in rice. A type of alternative splicing (AS), distinctive from all five previously known splicing types, was identified in which interior sequences of a constitutive exon could be spliced. Translation of the transcript produced with this AS type was demonstrated at the protein level. Expression of multiple transcripts was organ specific. The expression abundance of transcripts, OsRIX4-4 and OsRIX4-5, was positively correlated with fertility in rice. The splicing type identified in the present study provided the means to further understand and define different mRNA splicing types in plants and suggested that post-transcription processing of mRNA and its regulation mechanism are complex.

  2. Daily physical activity and type 2 diabetes: A review

    Institute of Scientific and Technical Information of China (English)

    Hidetaka; Hamasaki

    2016-01-01

    Physical activity improves glycemic control and reduces the risk of cardiovascular disease(CVD) and mortality in patients with type 2 diabetes(T2D). Moderate to vigorous physical activity is recommended to manage T2D; however, patients with T2D can be physically weak, making it difficult to engage in the recommended levels of physical activity. Daily physical activity includes various activities performed during both occupational and leisure time such as walking, gardening, and housework that type 2 diabetic patients should be able to perform without considerable physical burden. This review focuses on the association between daily physical activity and T2D. Walking was the most common form of daily physical activity, with numerous studies demonstrating its beneficial effects on reducing the risk of T2D, CVD, and mortality. Walking for at least 30 min per day was shown to reduce the risk of T2D by approximately 50%. Additionally, walking was associated with a reduction in mortality. In contrast, evidence was extremely limited regarding other daily physical activities such as gardening and housework in patients with T2D. Recent studies have suggested daily physical activity, including non-exercise activity thermogenesis, to be favorably associated with metabolic risks and mortality. However, well-designed longitudinal studies are warranted to elucidate its effects on overall health.

  3. Identification of genes for complex diseases using integrated analysis of multiple types of genomic data.

    Directory of Open Access Journals (Sweden)

    Hongbao Cao

    Full Text Available Various types of genomic data (e.g., SNPs and mRNA transcripts have been employed to identify risk genes for complex diseases. However, the analysis of these data has largely been performed in isolation. Combining these multiple data for integrative analysis can take advantage of complementary information and thus can have higher power to identify genes (and/or their functions that would otherwise be impossible with individual data analysis. Due to the different nature, structure, and format of diverse sets of genomic data, multiple genomic data integration is challenging. Here we address the problem by developing a sparse representation based clustering (SRC method for integrative data analysis. As an example, we applied the SRC method to the integrative analysis of 376821 SNPs in 200 subjects (100 cases and 100 controls and expression data for 22283 genes in 80 subjects (40 cases and 40 controls to identify significant genes for osteoporosis (OP. Comparing our results with previous studies, we identified some genes known related to OP risk (e.g., 'THSD4', 'CRHR1', 'HSD11B1', 'THSD7A', 'BMPR1B' 'ADCY10', 'PRL', 'CA8','ESRRA', 'CALM1', 'CALM1', 'SPARC', and 'LRP1'. Moreover, we uncovered novel osteoporosis susceptible genes ('DICER1', 'PTMA', etc. that were not found previously but play functionally important roles in osteoporosis etiology from existing studies. In addition, the SRC method identified genes can lead to higher accuracy for the diagnosis/classification of osteoporosis subjects when compared with the traditional T-test and Fisher-exact test, which further validates the proposed SRC approach for integrative analysis.

  4. Identification of genes for complex diseases using integrated analysis of multiple types of genomic data.

    Science.gov (United States)

    Cao, Hongbao; Lei, Shufeng; Deng, Hong-Wen; Wang, Yu-Ping

    2012-01-01

    Various types of genomic data (e.g., SNPs and mRNA transcripts) have been employed to identify risk genes for complex diseases. However, the analysis of these data has largely been performed in isolation. Combining these multiple data for integrative analysis can take advantage of complementary information and thus can have higher power to identify genes (and/or their functions) that would otherwise be impossible with individual data analysis. Due to the different nature, structure, and format of diverse sets of genomic data, multiple genomic data integration is challenging. Here we address the problem by developing a sparse representation based clustering (SRC) method for integrative data analysis. As an example, we applied the SRC method to the integrative analysis of 376821 SNPs in 200 subjects (100 cases and 100 controls) and expression data for 22283 genes in 80 subjects (40 cases and 40 controls) to identify significant genes for osteoporosis (OP). Comparing our results with previous studies, we identified some genes known related to OP risk (e.g., 'THSD4', 'CRHR1', 'HSD11B1', 'THSD7A', 'BMPR1B' 'ADCY10', 'PRL', 'CA8','ESRRA', 'CALM1', 'CALM1', 'SPARC', and 'LRP1'). Moreover, we uncovered novel osteoporosis susceptible genes ('DICER1', 'PTMA', etc.) that were not found previously but play functionally important roles in osteoporosis etiology from existing studies. In addition, the SRC method identified genes can lead to higher accuracy for the diagnosis/classification of osteoporosis subjects when compared with the traditional T-test and Fisher-exact test, which further validates the proposed SRC approach for integrative analysis.

  5. Multiple forms of endopeptidase activity from jojoba seeds.

    Science.gov (United States)

    Wolf, M J; Storey, R D

    1990-01-01

    The cotyledons of 27 day post-germination jojoba seedlings (Simmondsia chinensis) contained five distinct endopeptidase activities separable by DEAE Bio-Gel and CM-cellulose ion exchange chromatography. The endopeptidases were purified 108- to 266-fold and their individuality was confirmed by activity-specific assays in native acrylamide gels along with differences in their Mr and catalytic properties. The five endopeptidases, which showed activity on model substrates and protein, were named EP Ia, EP Ib, EP II, EP III and EP IV. EP Ia was a serine proteinase with a pH optimum of ca 8 and Mr of 58,000. EP Ib, II and III were discrete cysteine proteinases showing pH optima of ca 6.8, 6.0 and 5.4 and Mr of 41,000, 47,000 and 35,000 respectively. EP IV was an aspartic acid proteinase with a ca pH optimum of 3.5 and Mr of 33,000.

  6. Whole-Body MRI versus PET in assessment of multiple myeloma disease activity.

    LENUS (Irish Health Repository)

    Shortt, Conor P

    2009-04-01

    The purpose of this study was to compare FDG PET; whole-body MRI; and the reference standard, bone marrow aspiration and biopsy, to determine the best imaging technique for assessment of disease activity in multiple myeloma.

  7. The Long and the Short of It: Comments on Multiple Timescale Studies of Human Activity.

    Science.gov (United States)

    Lemke, Jay L.

    2001-01-01

    Comments on four articles in a special issue of the Journal of the Learning Sciences on methodology in learning sciences. Analyzes the articles within a general model seeking to analyze human activity across multiple time scales. (Author/MM)

  8. STATISTICAL METHODOLOGY FOR THE SIMULTANEOUS ANALYSIS OF MULTIPLE TYPES OF OUTCOMES IN NONLINEAR THRESHOLD MODELS.

    Science.gov (United States)

    Multiple outcomes are often measured on each experimental unit in toxicology experiments. These multiple observations typically imply the existence of correlation between endpoints, and a statistical analysis that incorporates it may result in improved inference. When both disc...

  9. Regulation of tissue-type plasminogen activator and plasminogen activator inhibitor type-1 in cultured rat Sertoli and Leydig cells

    Institute of Scientific and Technical Information of China (English)

    刘以训; 杜群; 周红明; 刘奎; 胡召元

    1996-01-01

    New data are provided to show that (i) rat Sertoli cells produce two types of plasminogen activators, tissue type (tPA) and urokinase type (uPA), and a plasminogen activator inhibitor type-1 (PAI-1); (ii) both tPA (but not uPA) and PAI-1 secretion in the culture are modified by FSH, forskolin, dbcAMP, GnRH, PMA and growth factors (EGF and FGF), but not by hCG and androstenedione (△4); (iii) in vitro secretion of tPA and PA-PAI-1 complexes of Sertoli cells are greatly enhanced by presence of Leydig cells which produce negligible tPA but measurable PAI-1 activity;(iv) combination culture of Sertoli and Leydig cells remarkably increases FSH-induced PAI-1 activity and decreases hCG- and forskolin-induced inhibitor activity as compared with that of two cell types cultured alone. These data suggest that rat Sertoli cells, similar to ovarian granulosa cells, are capable of secreting both tPA and uPA, as well as PAI-1. The interaction of Sertoli cells and Leydig cells is essential for the cells to response to

  10. Twist1 activity thresholds define multiple functions in limb development

    OpenAIRE

    Krawchuk, Dayana; Weiner, Shoshana J; Chen, You-Tzung; Lu, Benson; Costantini, Frank; Behringer, Richard R.; Laufer, Ed

    2010-01-01

    The basic helix-loop-helix transcription factor Twist1 is essential for normal limb development. Twist1−/− embryos die at midgestation. However, studies on early limb buds found that Twist1−/− mutant limb mesenchyme has an impaired response to FGF signaling from the apical ectodermal ridge, which disrupts the feedback loop between the mesenchyme and AER, and reduces and shifts anteriorly Shh expression in the zone of polarizing activity. We have combined Twist1 null, hypomorph and conditional...

  11. Activated mechanisms in proteins: a multiple-temperature activation-relaxation technique study

    Science.gov (United States)

    Malek, Rachid; Mousseau, Normand; Derreumaux, Philippe

    2001-03-01

    The low-temperature dynamics of proteins is controlled by a complex activated dynamics taking place over long time-scales compared with the period of thermal oscillations. In view of the range of relevant time scales, the numerical study of these processes remains a challenge and numerous methods have been introduced to address this problem. We introduce here a mixture of two algorithms, the activation-relaxation technique (ART)^1,2 coupled with the parallel tempering method, and use it to study the structure of the energy landscape around the native state of a 38-residue polypeptide. While ART samples rapidly the local energy landscape, the parallel tempering, which sets up exchanges of configuration between simultaneous runs at multiple temperatures, generates a very efficient sampling of energy basins separated by high barriers^(3). Results show the nature of the barriers and local minima surrounding the native state of this 38-residue peptide, modeled with off-lattice OPEP-like interactions^4. (1) G.T. Barkema and N. Mousseau, PRL 77, 4358 (1996) (2) N. Mousseau and G.T. Barkema, PRE 57, 2419 (1998) (3) E. Marinari and G. Parisi, Europhys. Lett., 19 (6), 451 (1992) (4) Ph. Derreumaux, J. Chem. Phys. 111, 2301 (1999); PRB 85, 206 (2000)

  12. The VLT-FLAMES Tarantula Survey. VIII. Multiplicity properties of the O-type star population

    Science.gov (United States)

    Sana, H.; de Koter, A.; de Mink, S. E.; Dunstall, P. R.; Evans, C. J.; Hénault-Brunet, V.; Maíz Apellániz, J.; Ramírez-Agudelo, O. H.; Taylor, W. D.; Walborn, N. R.; Clark, J. S.; Crowther, P. A.; Herrero, A.; Gieles, M.; Langer, N.; Lennon, D. J.; Vink, J. S.

    2013-02-01

    Context. The Tarantula Nebula in the Large Magellanic Cloud is our closest view of a starburst region and is the ideal environment to investigate important questions regarding the formation, evolution and final fate of the most massive stars. Aims: We analyze the multiplicity properties of the massive O-type star population observed through multi-epoch spectroscopy in the framework of the VLT-FLAMES Tarantula Survey. With 360 O-type stars, this is the largest homogeneous sample of massive stars analyzed to date. Methods: We use multi-epoch spectroscopy and variability analysis to identify spectroscopic binaries. We also use a Monte-Carlo method to correct for observational biases. By modeling simultaneously the observed binary fraction, the distributions of the amplitudes of the radial velocity variations and the distribution of the time scales of these variations, we constrain the intrinsic current binary fraction and period and mass-ratio distributions. Results: We observe a spectroscopic binary fraction of 0.35 ± 0.03, which corresponds to the fraction of objects displaying statistically significant radial velocity variations with an amplitude of at least 20 km s-1. We compute the intrinsic binary fraction to be 0.51 ± 0.04. We adopt power-laws to describe the intrinsic period and mass-ratio distributions: f(log 10P/d) ~ (log 10P/d)π (with log 10P/d in the range 0.15-3.5) and f(q) ~ qκ with 0.1 ≤ q = M2/M1 ≤ 1.0. The power-law indexes that best reproduce the observed quantities are π = -0.45 ± 0.30 and κ = -1.0 ± 0.4. The period distribution that we obtain thus favours shorter period systems compared to an Öpik law (π = 0). The mass ratio distribution is slightly skewed towards low mass ratio systems but remains incompatible with a random sampling of a classical mass function (κ = -2.35). The binary fraction seems mostly uniform across the field of view and independent of the spectral types and luminosity classes. The binary fraction in the outer

  13. Classification of types of stuttering symptoms based on brain activity.

    Science.gov (United States)

    Jiang, Jing; Lu, Chunming; Peng, Danling; Zhu, Chaozhe; Howell, Peter

    2012-01-01

    Among the non-fluencies seen in speech, some are more typical (MT) of stuttering speakers, whereas others are less typical (LT) and are common to both stuttering and fluent speakers. No neuroimaging work has evaluated the neural basis for grouping these symptom types. Another long-debated issue is which type (LT, MT) whole-word repetitions (WWR) should be placed in. In this study, a sentence completion task was performed by twenty stuttering patients who were scanned using an event-related design. This task elicited stuttering in these patients. Each stuttered trial from each patient was sorted into the MT or LT types with WWR put aside. Pattern classification was employed to train a patient-specific single trial model to automatically classify each trial as MT or LT using the corresponding fMRI data. This model was then validated by using test data that were independent of the training data. In a subsequent analysis, the classification model, just established, was used to determine which type the WWR should be placed in. The results showed that the LT and the MT could be separated with high accuracy based on their brain activity. The brain regions that made most contribution to the separation of the types were: the left inferior frontal cortex and bilateral precuneus, both of which showed higher activity in the MT than in the LT; and the left putamen and right cerebellum which showed the opposite activity pattern. The results also showed that the brain activity for WWR was more similar to that of the LT and fluent speech than to that of the MT. These findings provide a neurological basis for separating the MT and the LT types, and support the widely-used MT/LT symptom grouping scheme. In addition, WWR play a similar role as the LT, and thus should be placed in the LT type.

  14. Classification of types of stuttering symptoms based on brain activity.

    Directory of Open Access Journals (Sweden)

    Jing Jiang

    Full Text Available Among the non-fluencies seen in speech, some are more typical (MT of stuttering speakers, whereas others are less typical (LT and are common to both stuttering and fluent speakers. No neuroimaging work has evaluated the neural basis for grouping these symptom types. Another long-debated issue is which type (LT, MT whole-word repetitions (WWR should be placed in. In this study, a sentence completion task was performed by twenty stuttering patients who were scanned using an event-related design. This task elicited stuttering in these patients. Each stuttered trial from each patient was sorted into the MT or LT types with WWR put aside. Pattern classification was employed to train a patient-specific single trial model to automatically classify each trial as MT or LT using the corresponding fMRI data. This model was then validated by using test data that were independent of the training data. In a subsequent analysis, the classification model, just established, was used to determine which type the WWR should be placed in. The results showed that the LT and the MT could be separated with high accuracy based on their brain activity. The brain regions that made most contribution to the separation of the types were: the left inferior frontal cortex and bilateral precuneus, both of which showed higher activity in the MT than in the LT; and the left putamen and right cerebellum which showed the opposite activity pattern. The results also showed that the brain activity for WWR was more similar to that of the LT and fluent speech than to that of the MT. These findings provide a neurological basis for separating the MT and the LT types, and support the widely-used MT/LT symptom grouping scheme. In addition, WWR play a similar role as the LT, and thus should be placed in the LT type.

  15. Cherubism associated with neurofibromatosis type 1, and multiple osteolytic lesions of both femurs: A previously undescribed association of findings

    Energy Technology Data Exchange (ETDEWEB)

    Martinez-Tello, Francisco J. [Hospital Universitario ' ' 12 de Octubre' ' , Departamento de Anatomia Patologica, Madrid (Spain); Manjon-Luengo, Palmira [Hospital Universitario ' ' 12 de Octubre' ' , Department of Radiology, Madrid (Spain); Martin-Perez, Manuel [Hospital Universitario ' ' 12 de Octubre' ' , Department of Pathology, Madrid (Spain); Montes-Moreno, Santiago

    2005-12-01

    We present a patient with neurofibromatosis type 1, with the clinical, radiological and histological features of cherubism mandibular lesions, and multiple osteolytic, geographic lesions in both femurs, consistent with multiple non-ossifying fibromas. We have been unable to find a similar case in the world literature. We discuss our findings in relationship with a number of syndromes that present clinical, radiological or pathological similarities. (orig.)

  16. Comparing evaluation activities across multiple theories of practice.

    Science.gov (United States)

    Dillman, Lisa M

    2013-06-01

    This article compares and contrasts the evaluation activities described in Practical Participatory Evaluation (Cousins & Whitmore, 1998), Values-engaged Evaluation (Greene, 2005), and Emergent Realist Evaluation (Mark, Henry, & Julnes, 1998). Using the logic models developed to depict each of the three evaluation theories (Hansen, Alkin, & Wallace, 2013) as a starting point, both quantitative and qualitative analysis techniques are employed to discuss the similarities and differences across the practice prescriptions. The approaches are then described according to Miller's (2010) standards for empirical examinations of evaluation theory. Specifically, I offer speculation about their operational specificity and feasibility in practice. I argue that none of the models is completely specific, or wholly unique, and they all present challenges of adaptation into the field. However, the models each offer varying degrees of guidance and unique elements through their prescriptions.

  17. The levels of English teachers at primary schools to employ materials and activities based on multiple intelligences theory (Malatya sample

    Directory of Open Access Journals (Sweden)

    Nihat ŞAD

    2008-06-01

    Full Text Available This study aims at investigating the levels of English teachers to employ materials and activities based on multiple intelligences theory by some variables. The population comprises 176 English teachers from 80 primary schools in Malatya city center during 2006-2007. The participants are 102 English teachers from 32 primary schools chosen randomly. A scale developed by the researcher was used as the medium. The data was analyzed using frequency, percentage, t-test, ANOVA, and LSD analysis. Results showed English teachers utilize multiple-intelligences theory at moderate level and cannot devote balanced importance to intelligence types. Moreover no significant difference was observed in terms of gender, the program of graduation, and seniority, while there was a significant difference in terms of type of school in favor of private schools.

  18. Multiple types of cerebellar target neurons and their circuitry in the vestibulo-ocular reflex.

    Science.gov (United States)

    Shin, Minyoung; Moghadam, Setareh H; Sekirnjak, Chris; Bagnall, Martha W; Kolkman, Kristine E; Jacobs, Richard; Faulstich, Michael; du Lac, Sascha

    2011-07-27

    The cerebellum influences behavior and cognition exclusively via Purkinje cell synapses onto neurons in the deep cerebellar and vestibular nuclei. In contrast with the rich information available about the organization of the cerebellar cortex and its synaptic inputs, relatively little is known about microcircuitry postsynaptic to Purkinje cells. Here we examined the cell types and microcircuits through which Purkinje cells influence an oculomotor behavior controlled by the cerebellum, the horizontal vestibulo-ocular reflex, which involves only two eye muscles. Using a combination of anatomical tracing and electrophysiological recordings in transgenic mouse lines, we identified several classes of neurons in the medial vestibular nucleus that receive Purkinje cell synapses from the cerebellar flocculus. Glycinergic and glutamatergic flocculus target neurons (FTNs) with somata densely surrounded by Purkinje cell terminals projected axons to the ipsilateral abducens and oculomotor nuclei, respectively. Of three additional types of FTNs that were sparsely innervated by Purkinje cells, glutamatergic and glycinergic neurons projected to the contralateral and ipsilateral abducens, respectively, and GABAergic neurons projected to contralateral vestibular nuclei. Densely innervated FTNs had high spontaneous firing rates and pronounced postinhibitory rebound firing, and were physiologically homogeneous, whereas the intrinsic excitability of sparsely innervated FTNs varied widely. Heterogeneity in the molecular expression, physiological properties, and postsynaptic targets of FTNs implies that Purkinje cell activity influences the neural control of eye movements in several distinct ways. These results indicate that the cerebellum regulates a simple reflex behavior via at least five different cell types that are postsynaptic to Purkinje cells.

  19. Clinical value of tumor doubling estimations in multiple endocrine neoplasia type II.

    Science.gov (United States)

    Jackson, C E; Talpos, G B; Block, M A; Norum, R A; Lloyd, R V; Tashjian, A H

    1984-12-01

    Experience with children with multiple endocrine neoplasia (MEN) type IIb has emphasized that medullary thyroid cancer (MTC) in MEN IIb is more aggressive than in MEN IIa. Earlier ages of onset and apparently more rapid growth of MTC in MEN IIb suggest that these tumors have earlier ages of conversion to malignant states and/or shorter doubling times. The age at which a hyperplastic C cell becomes a malignant cell and the true doubling time cannot be estimated presently. Maximum volume-doubling times of 35 and 75 days (21 to 26 doublings) were calculated from tumor size and age at operation in five patients with MEN IIb aged 2 to 5 years. Calculations in 20 patients with MEN IIa revealed maximum doubling times of 110 to 440 days, with ages ranging from 7 to 29 years and number of doubling ranging from 18 to 38. Positive provocative calcitonin tests in two adult patients with MEN IIa after 10 to 11 years of repeated negative tests suggest a minimum doubling time of 190 to 210 days. Such experience emphasizes that negative stimulated calcitonin tests less than 11 years after operation do not provide assurance of cures for MTC in MEN IIa although negative tests after more than 5 years for MEN IIb are encouraging. Calculations of volume doublings accounting for various-sized tumors are compatible with Knudson's two-mutational-event theory on the initiation of neoplasia.

  20. Association between a genetic variant of type-1 cannabinoid receptor and inflammatory neurodegeneration in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Silvia Rossi

    Full Text Available Genetic ablation of type-1 cannabinoid receptors (CB1Rs exacerbates the neurodegenerative damage of experimental autoimmune encephalomyelitis, the rodent model of multiple sclerosis (MS. To address the role on CB1Rs in the pathophysiology of human MS, we first investigated the impact of AAT trinucleotide short tandem repeat polymorphism of CNR1 gene on CB1R cell expression, and secondly on the inflammatory neurodegeneration process responsible for irreversible disability in MS patients. We found that MS patients with long AAT repeats within the CNR1 gene (≥12 in both alleles had more pronounced neuronal degeneration in response to inflammatory white matter damage both in the optic nerve and in the cortex. Optical Coherence Tomography (OCT, in fact, showed more severe alterations of the retinal nerve fiber layer (RNFL thickness and of the macular volume (MV after an episode of optic neuritis in MS patients carrying the long AAT genotype of CNR1. MS patients with long AAT repeats also had magnetic resonance imaging (MRI evidence of increased gray matter damage in response to inflammatory lesions of the white matter, especially in areas with a major role in cognition. In parallel, visual abilities evaluated at the low contrast acuity test, and cognitive performances were negatively influenced by the long AAT CNR1 genotype in our sample of MS patients. Our results demonstrate the biological relevance of the (AATn CNR1 repeats in the inflammatory neurodegenerative damage of MS.

  1. Effect of Intensive Therapy of Multiple Factors Intervention on Vascular Complications in Type 2 Diabetes

    Institute of Scientific and Technical Information of China (English)

    吴汉妮; 张淑玲; 沈迪

    2003-01-01

    The effects of intensive versus regular therapy on incidence and progress of microalbuminuria in type 2 diabetes were compared. During a follow-up of 3 years, 96 cases of diabetes mellitus were randomized to intensive and regular therapy groups. HbA1c goal was same in the two groups,but the goal of blood pressure (Bp) and lipid was more strict in the intensive therapy group than in the regular therapy group. There was statistically significant difference in the incidence and progression of vascular complications between the two groups. Logistic stepwise-regression analysis (odds ration, OR) showed that there was significant difference in the progression of nephropathy (OR 0. 24,95 % CI 0. 12-0. 76), retinopathy (OR 0.38, 95 % CI 0.16-0. 88), peripheral neuropathy (OR 0. 42, 95 % CI 0. 22-0. 86) and autonomic neuropathy (OR 0. 29, 95 % CI 0. 12-0. 86) between the two groups (P<0. 01). It was concluded that intensive blood glucose controlling could retard diabetic vascular complications. Intensive therapy of multiple factors interventions (controlling Bp, regulating blood lipid, improving microcirculation) could decrease various risk factors for diabetic vascular complications.

  2. Radiofrequency Ablation and Excision of Multiple Cutaneous Lesions in Neurofibromatosis Type 1

    Directory of Open Access Journals (Sweden)

    Seong-Hun Kim

    2013-01-01

    Full Text Available Background Von Recklinghausen disease or neurofibromatosis type 1 is an autosomaldominant genetic disorder of chromosome 17q11.2. The most common characteristic findingsof NF 1 include multiple and recurrent cutaneous neurofibromas associated with psychosocialdistress.Methods Sixteen patients (9 female, 7 male; average age, 31 years; range, 16 to 67 years withmultiple cutaneous neurofibromas between March 2010 and February 2012 were includedin the study. All patients were treated with radiosurgical ablation and excision under generalanesthesia.Results All 16 patients were satisfied with the results, when questioned directly during theoutpatient department follow-up. The only complaint from a few patients was minimalscarring, but acceptable results were obtained in the end.Conclusions The radiofrequency procedure is almost bloodless and quick, creating a smallernecrotizing zone. Therefore, instead of employing the time consuming traditional surgery,such as laser therapy and electrosurgical excision, that produces uncertain results and canaffect normal adjacent tissue, treatment of neurofibromas with radiofrequency ablationand excision can be an alternative choice of treatment for patients with a large number ofneurofibromas.

  3. An endothelial storage granule for tissue-type plasminogen activator

    NARCIS (Netherlands)

    Emeis, J.J.; Eijnden van den - Schrauwen, Y.; Hoogen, C.M. van den; Priester, W. de; Westmuckett, A.; Lupu, F.

    1997-01-01

    In previous studies we have shown that, after stimulation by a receptor ligand such as thrombin, tissue-type plasminogen activator (tPA) and von Willebrand factor (vW(f)) will be acutely released from human umbilical vein endothelial cells (HUVEC). However, the mechanisms involved in the secretion o

  4. Correlation of mutant menin stability with clinical expression of multiple endocrine neoplasia type 1 and its incomplete forms.

    Science.gov (United States)

    Shimazu, Satoko; Nagamura, Yuko; Yaguchi, Hiroko; Ohkura, Naganari; Tsukada, Toshihiko

    2011-11-01

    Germline mutations of the tumor suppressor gene MEN1 are found not only in typical multiple endocrine neoplasia type 1 (MEN1) but also in its incomplete forms such as familial isolated hyperparathyroidism (FIHP) and apparently sporadic parathyroid tumor (ASPT). No definitive genotype-phenotype correlation has been established between these clinical forms and MEN1 gene mutations. We previously demonstrated that mutant menin proteins associated with MEN1 are rapidly degraded by the ubiquitin-proteasome pathway. To examine whether the intracellular stability of mutant menin is correlated with clinical phenotypes, we developed a method of evaluating menin stability and examined 20 mutants associated with typical MEN1 (17 missense, two in-frame deletion, one nonsense) and 21 mutants associated with FIHP or ASPT (19 missense, two in-frame deletion). All tested mutants associated with typical MEN1 showed reduced stability. Some missense and in-frame deletion mutants (G28A, R171W, T197I, E255K, E274A, Y353del and E366D) associated with FIHP or ASPT were almost as stable as or only slightly less stable than wild-type menin, while others were as unstable as those associated with typical MEN1. Some stable mutants exhibited substantial biological activities when tested by JunD-dependent transactivation assay. These findings suggest that certain missense and in-frame mutations are fairly stable and retain intrinsic biological activity, and might be specifically associated with incomplete clinical phenotypes. The menin stability test will provide useful information for the management of patients carrying germline MEN1 mutations especially when they have missense or in-frame variants of ambiguous clinical significance.

  5. Psychedelics Recruit Multiple Cellular Types and Produce Complex Transcriptional Responses Within the Brain.

    Science.gov (United States)

    Martin, David A; Nichols, Charles D

    2016-09-01

    There has recently been a resurgence of interest in psychedelics, substances that profoundly alter perception and cognition and have recently demonstrated therapeutic efficacy to treat anxiety, depression, and addiction in the clinic. The receptor mechanisms that drive their molecular and behavioral effects involve activation of cortical serotonin 5-HT2A receptors, but the responses of specific cellular populations remain unknown. Here, we provide evidence that a small subset of 5-HT2A-expressing excitatory neurons is directly activated by psychedelics and subsequently recruits other select cell types including subpopulations of inhibitory somatostatin and parvalbumin GABAergic interneurons, as well as astrocytes, to produce distinct and regional responses. To gather data regarding the response of specific neuronal populations, we developed methodology for fluorescence-activated cell sorting (FACS) to segregate and enrich specific cellular subtypes in the brain. These methods allow for robust neuronal sorting based on cytoplasmic epitopes followed by downstream nucleic acid analysis, expanding the utility of FACS in neuroscience research.

  6. Psychedelics Recruit Multiple Cellular Types and Produce Complex Transcriptional Responses Within the Brain

    Directory of Open Access Journals (Sweden)

    David A. Martin

    2016-09-01

    Full Text Available There has recently been a resurgence of interest in psychedelics, substances that profoundly alter perception and cognition and have recently demonstrated therapeutic efficacy to treat anxiety, depression, and addiction in the clinic. The receptor mechanisms that drive their molecular and behavioral effects involve activation of cortical serotonin 5-HT2A receptors, but the responses of specific cellular populations remain unknown. Here, we provide evidence that a small subset of 5-HT2A-expressing excitatory neurons is directly activated by psychedelics and subsequently recruits other select cell types including subpopulations of inhibitory somatostatin and parvalbumin GABAergic interneurons, as well as astrocytes, to produce distinct and regional responses. To gather data regarding the response of specific neuronal populations, we developed methodology for fluorescence-activated cell sorting (FACS to segregate and enrich specific cellular subtypes in the brain. These methods allow for robust neuronal sorting based on cytoplasmic epitopes followed by downstream nucleic acid analysis, expanding the utility of FACS in neuroscience research.

  7. Activity trends in young solar-type stars

    CERN Document Server

    Lehtinen, Jyri; Hackman, Thomas; Kajatkari, Perttu; Henry, Gregory W

    2015-01-01

    We apply the Continuous Period Search (CPS) time series analysis method on Johnson B and V band photometry of 21 young and active solar-type, collected over 16 to 27 years and characterize the behaviour of their activity. Using the CPS method, differential rotation could be estimated from the observed variations of the photometric rotation period. Active longitudes were retrieved by applying a non-parametric period search on the light curve minimum epochs, and activity cycles by applying a secondary period search on the modelled light curve mean and amplitude values. We supplemented the time series results by calculating new $\\log{R'_{\\rm HK}}$ emission indices for the stars from high resolution spectroscopy. The measurements of the photometric rotation period variations point to a trend of increasing differential rotation coefficients towards longer rotation periods but do not reveal any dependence from the effective temperature of the stars. The secondary period searches revealed activity cycles in 18 of th...

  8. DMPD: Multiple signaling pathways leading to the activation of interferon regulatoryfactor 3. [Dynamic Macrophage Pathway CSML Database

    Lifescience Database Archive (English)

    Full Text Available 12213596 Multiple signaling pathways leading to the activation of interferon regula...(.html) (.csml) Show Multiple signaling pathways leading to the activation of interferon regulatoryfactor 3.... PubmedID 12213596 Title Multiple signaling pathways leading to the activation of

  9. Social Trust and Types of Classroom Activities: Predictors of Language Learning Motivation

    Directory of Open Access Journals (Sweden)

    Hossein Khodabakhshzadeh

    2017-01-01

    Full Text Available The present study examined the role of social trust and types of classroom activities as some probable significant predictors of language learning motivation on a sample of 200 Iranian EFL upper-intermediate learners who have been selected randomly. Consequently, the participants completed three questionnaires, Language Learning Motivation Inventory, Classroom and school Community Inventory, and Classroom Activities Inventory, the reliability and validity of each have been checked previously. After running Multiple Regression through SPSS Software, the results revealed that social trust and types of classroom activities accounted for 16.7% of the variance in language learning motivation. Although each of them had a unique impact on language learning motivation, "Deep Language Use" as one of the types of classroom activities had a greater contribution to English as a foreign language learning motivation (002< .05, outweighing social trust as a more important predictor, (.005 < .05. Finally, pedagogical implications along with suggestions for further studies are discussed. Keywords: Types of classroom activities, Social trust, Language learning motivation, EFL learners

  10. MytiLec, a Mussel R-Type Lectin, Interacts with Surface Glycan Gb3 on Burkitt’s Lymphoma Cells to Trigger Apoptosis through Multiple Pathways

    Directory of Open Access Journals (Sweden)

    Imtiaj Hasan

    2015-12-01

    Full Text Available MytiLec; a novel lectin isolated from the Mediterranean mussel (Mytilus galloprovincialis; shows strong binding affinity to globotriose (Gb3: Galα1-4Galβ1-4Glc. MytiLec revealed β-trefoil folding as also found in the ricin B-subunit type (R-type lectin family, although the amino acid sequences were quite different. Classification of R-type lectin family members therefore needs to be based on conformation as well as on primary structure. MytiLec specifically killed Burkitt's lymphoma Ramos cells, which express Gb3. Fluorescein-labeling assay revealed that MytiLec was incorporated inside the cells. MytiLec treatment of Ramos cells resulted in activation of both classical MAPK/ extracellular signal-regulated kinase and extracellular signal-regulated kinase (MEK-ERK and stress-activated (p38 kinase and JNK Mitogen-activated protein kinases (MAPK pathways. In the cells, MytiLec treatment triggered expression of tumor necrosis factor (TNF-α (a ligand of death receptor-dependent apoptosis and activation of mitochondria-controlling caspase-9 (initiator caspase and caspase-3 (activator caspase. Experiments using the specific MEK inhibitor U0126 showed that MytiLec-induced phosphorylation of the MEK-ERK pathway up-regulated expression of the cyclin-dependent kinase inhibitor p21, leading to cell cycle arrest and TNF-α production. Activation of caspase-3 by MytiLec appeared to be regulated by multiple different pathways. Our findings, taken together, indicate that the novel R-type lectin MytiLec initiates programmed cell death of Burkitt’s lymphoma cells through multiple pathways (MAPK cascade, death receptor signaling; caspase activation based on interaction of the lectin with Gb3-containing glycosphingolipid-enriched microdomains on the cell surface.

  11. Assisting people with multiple disabilities to improve computer typing efficiency through a mouse wheel and on-screen keyboard software.

    Science.gov (United States)

    Shih, Ching-Hsiang

    2014-09-01

    The main purpose of this study was to find out whether three students with multiple disabilities could increase their keyboard typing performance by poking the standard mouse scroll wheel with the newly developed Dynamic Typing Assistive Program (DTAP) and the built-in On-Screen Keyboard (OSK) computer software. The DTAP is a software solution that allows users to complete typing tasks with OSK software easily, quickly, and accurately by poking the mouse wheel. This study was performed according to a multiple baseline design across participants, and the experimental data showed that all of the participants significantly increased their typing efficiency in the intervention phase. Moreover, this improved performance was maintained during the maintenance phase. Practical and developmental implications of the findings were discussed.

  12. Multiple or familial café-au-lait spots is neurofibromatosis type 6: clarification of a diagnosis.

    Science.gov (United States)

    Madson, Justin G

    2012-05-15

    A café-au-lait macule (CALM) is an evenly pigmented macule or patch of variable size. Solitary CALMs are common birthmarks in up to 2.5 percent of normal neonates and their incidence rises to up to 25 percent in preschool-aged children. Two or more CALMs occur much less frequently. Multiple lesions may warrant investigation to identify an underlying disease including neurofibromatosis types 1 (NF1), neurofibromatosis type 2, McCune-Albright syndrome, and neurofibromatosis type 1-like syndrome. Considered a hallmark and diagnostic criteria for NF1 is the presence of 6 or more CALMs greater than 0.5 cm in prepubertal individuals. Rare reports describe families which demonstrate the phenomenon of multiple CALMs without other stigmata of NF1 or evidence of other systemic disease. Herein is a description of the condition and justification for this entity to be named Neurofibromatosis type 6.

  13. Evaluation of Seismic Performance and Effectiveness of Multiple Slim-Type Damper System for Seismic Response Control of Building Structures

    Directory of Open Access Journals (Sweden)

    David Kim

    2014-01-01

    Full Text Available This paper presents the evaluation of seismic performance and cost-effectiveness of a multiple slim-type damper system developed for the vibration control of earthquake excited buildings. The multiple slim-type damper (MSD that consists of several small slim-type dampers and linkage units can control damping capacity easily by changing the number of small dampers. To evaluate the performance of the MSD, dynamic loading tests are performed with three slim-type dampers manufactured at a real scale. Numerical simulations are also carried out by nonlinear time history analysis with a ten-story earthquake excited building structure. The seismic performance and cost-effectiveness of the MSD system are investigated according to the various installation configurations of the MSD system. From the results of numerical simulation and cost-effectiveness evaluation, it is shown that combinations of the MSD systems can effectively improve the seismic performance of earthquake excited building structures.

  14. Activated Type 2 Innate Lymphoid Cells regulate Beige Fat Biogenesis

    Science.gov (United States)

    Lee, Min-Woo; Odegaard, Justin I.; Mukundan, Lata; Qiu, Yifu; Molofsky, Ari B.; Nussbaum, Jesse C.; Yun, Karen; Locksley, Richard M.; Chawla, Ajay

    2014-01-01

    SUMMARY Type 2 innate lymphoid cells (ILC2s), an innate source of the type 2 cytokines interleukin (IL)-5 and -13, participate in the maintenance of tissue homeostasis. Although type 2 immunity is critically important for mediating metabolic adaptations to environmental cold, the functions of ILC2s in beige or brown fat development are poorly defined. We report here that activation of ILC2s by IL-33 is sufficient to promote the growth of functional beige fat in thermoneutral mice. Mechanistically, ILC2 activation results in the proliferation of bipotential adipocyte precursors (APs) and their subsequent commitment to the beige fat lineage. Loss- and gain-of-function studies reveal that ILC2-and eosinophil-derived type 2 cytokines stimulate signaling via the IL-4Rα in PDGFRα+ APs to promote beige fat biogenesis. Together, our results highlight a critical role for ILC2s and type 2 cytokines in the regulation of adipocyte precursor numbers and fate, and as a consequence, adipose tissue homeostasis. PMID:25543153

  15. Physical Activity in Adolescent Females with Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Bahareh Schweiger

    2010-01-01

    Full Text Available Objective. We sought to identify amount of physical activity and relationship of physical activity to glycemic control among adolescent females 11 to 19 years of age with type 1 diabetes mellitus (T1DM. We also sought to evaluate associations of age and ethnicity with physical activity levels. Research Design and Methods. Adolescent females ages 11–19 years (n=203 were recruited during their outpatient diabetes appointment. Physical activity was obtained by self-report and was categorized as the number of days subjects had accumulated 60 minutes of moderate-to-vigorous physical activity during the past 7 days and for a typical week. Results. Girls reported being physically active for at least 60 minutes per day on 2.7±2.3 days in the last week, and on 3.1±2.2 days in a typical week. A greater number of physically active days in a typical week were associated with lower A1c (P=.049 in linear regression analysis. Conclusion. Adolescent females with T1DM report exercising for at least 60 minutes about 3 days per week, which does not meet the international recommendations of 60 minutes of moderate-to-vigorous activity per day. It is particularly important that adolescent girls with T1DM be encouraged to exercise since a greater number of physically active days per week is associated with better glycemic control.

  16. A Multiple Functional Protein: the Herpes Simplex Virus Type 1 Tegument Protein VP22

    Institute of Scientific and Technical Information of China (English)

    Mei-li LI; Hong GUO; Qiong DING; Chun-fu ZHENG

    2009-01-01

    The herpes simplex virus type 1 (HSV-1) VP22, is one of the most abundant HSV-1 tegument proteins with an average stoichiometry of 2 400 copies per virion and conserved among alphaherpesvirinae. Many functions are attributed to VP22, including nuclear localization, chromatin binding, microtubule binding, induction of microtubule reorganization, intercellular transport, interaction with cellular proteins, such as template activating factor I (TAF-I) and nonmuscle myosin II A (NMIIA), and viral proteins including tegument protein VP16, pUS9 and pUL46, glycoprotein E (gE) and gD. Recently, many novel functions performed by the HSV-1 VP22 protein have been shown, including promotion of protein synthesis at late times in infection, accumulation of a subset of viral mRNAs at early times in infection and possible transcriptional regulation function.

  17. Photocatalytic activity of glass ceramics containing Nasicon-type crystals

    Energy Technology Data Exchange (ETDEWEB)

    Fu, Jie, E-mail: fu@ohara-inc.co.jp [R and D Department, Ohara Inc., Sagamihara-shi, Kanagawa 252-5286 (Japan)

    2013-01-15

    Graphical abstract: Display Omitted Highlights: ► Glass ceramics containing Nasicon-type crystals were prepared. ► The glass ceramics showed photocatalytic activity under UV irradiation. ► Higher activity was observed in the MgTi{sub 4}(PO{sub 4}){sub 6}- and CaTi{sub 4}(PO{sub 4}){sub 6}-containing glass ceramics. -- Abstract: Glass ceramics were prepared by heat-treating MO–TiO{sub 2}–P{sub 2}O{sub 5} (M = Mg, Ca, Sr and Ba) and R{sub 2}O–TiO{sub 2}–P{sub 2}O{sub 5}–SiO{sub 2} (R = Li, Na and K) glasses, and their photocatalytic activity was investigated. The crystalline phases precipitated in the glasses were only Nasicon-type crystals, MTi{sub 4}(PO{sub 4}){sub 6} or RTi{sub 2}(PO{sub 4}){sub 3}. Decomposition experiments of both methylene blue (MB) and acetaldehyde showed that the glass ceramics exhibited effective photocatalytic activity. The activity did not depend on the radius of the M{sup 2+} or R{sup +} ion, and higher activity was observed in the MgTi{sub 4}(PO{sub 4}){sub 6} and CaTi{sub 4}(PO{sub 4}){sub 6} precipitated glass ceramics.

  18. PDGF-A promoter and enhancer elements provide efficient and selective antineoplastic gene therapy in multiple cancer types.

    Science.gov (United States)

    Mishra, A; Ormerod, A K; Cibull, M L; Spear, B T; Kraner, S D; Kaetzel, D M

    2009-04-01

    Development of antineoplastic gene therapies is impaired by a paucity of transcription control elements with efficient, cancer cell-specific activity. We investigated the utility of promoter (AChP) and 5'-distal enhancer (ACE66) elements from the platelet-derived growth factor-A (PDGF-A) gene, which are hyperactive in many human cancers. Efficacy of these elements was tested in multiple tumor cell lines, both in cell culture and as tumor explants in athymic nude mice. Plasmid and viral vectors were constructed with the AChP promoter alone or in fusion with three copies of the ACE66 enhancer for expression of the prototype suicide gene, thymidine kinase (TK). ACE/AChP and AChP cassettes elicited ganciclovir (GCV)-induced cytotoxicity in multiple tumor cell lines. The ACE enhancer element also exhibited synergism with placental and liver-specific promoter elements. An adenovirus containing the AChP-TK cassette produced striking increases in GCV sensitivity in cultured tumor cell lines, as well as GCV-induced regression of U87 MG glioblastoma explants in vivo. TK expression was distributed throughout tumors receiving the therapeutic virus, whereas TdT-mediated dUTP nick end labeling (TUNEL) analysis revealed numerous regions undergoing apoptosis. Vascularization and reticulin fiber networks were less pronounced in virus-GCV-treated tumors, suggesting that both primary and stromal cell types may have been targeted. These studies provide proof-of-principle for utility of the PDGF-A promoter and ACE66 enhancer in antineoplastic gene therapy for a diverse group of human cancers.

  19. Mating type loci of Sporisorium reilianum: novel pattern with three a and multiple b specificities.

    Science.gov (United States)

    Schirawski, Jan; Heinze, Bernadette; Wagenknecht, Martin; Kahmann, Regine

    2005-08-01

    Sporisorium reilianum and Ustilago maydis are two closely related smut fungi, which both infect maize but differ fundamentally in their mode of plant invasion and site of symptom development. As a prelude to studying the molecular basis of these differences, we have characterized the mating type loci of S. reilianum. S. reilianum has two unlinked mating type loci, a and b. Genes in both loci and adjacent regions show a high degree of synteny to the corresponding genes of U. maydis. The b locus occurs in at least five alleles and encodes two subunits of a heterodimeric homeodomain transcription factor, while the a locus encodes a pheromone/receptor system. However, in contrast to that of U. maydis, the a locus of S. reilianum exists in three alleles containing two active pheromone genes each. The alleles of the a locus appear to have arisen through recent recombination events within the locus itself. This has created a situation where each pheromone is specific for recognition by only one mating partner.

  20. Assimilating Multiple Data Types in the Community Land Model (CLM) for Deciduous Forests in North America

    Science.gov (United States)

    Montane, F.; Fox, A. M.; Hoar, T. J.; Arellano, A. F.; Liu, Y.; Moreno, G.; Quaife, T. L.; Richardson, A. D.; Trouet, V.; Alexander, M. R.; Chen, M.; Hollinger, D. Y.; Moore, D. J.

    2014-12-01

    Networks of eddy covariance towers like AmeriFlux provide the infrastructure necessary to study relationships between ecosystem processes and environmental forcing across a range of spatial and temporal scales. Recent syntheses of comparisons between observations from eddy covariance tower sites in North America and output from several Land Surface Models showed that the characterization of phenology was not accurate in most of the models. In order to improve phenological models, a continental-scale phenological observatory, the PhenoCam network, provides high-frequency observations of vegetation phenology, which can be used to derive a greenness index, the green chromatic coordinate (gcc). In this study we run the Community Land Model (CLM4.5) for 10 deciduous forests sites in North America, included in the AmeriFlux and PhenoCam networks, to assimilate multiple data types including one of the key variables in most ecosystem models, fPAR, the radiometric equivalent of Leaf Area Index (LAI). fPAR characterizes vegetation canopy function and energy absorption capacity and therefore it is important for estimating canopy photosynthesis. We use fPAR data from Moderate Resolution Imaging Spectroradiometer (MODIS), with a pixel resolution of 1 km x 1 km and a temporal resolution of 8 days. Data is assimilated in CLM with an Ensemble Kalman Filter, a sequential data assimilation technique, within the Data Assimilation Research Testbed (DART). In our study, we also compare observations available for Harvard Forest (LAI, NEE and gcc) with model output. The CLM output for LAI and NEE is sometimes located out of the observation space delimited by LAI and NEE measurements for Harvard Forest. After assimilating data, we compare observations and mean CLM model output from all the sites for a free run, an assimilation run and an assimilation run with inflation. We investigate the impact of assimilating these observations and the resultant model state updates on ecosystem carbon

  1. Indian hedgehog mutations causing brachydactyly type A1 impair Hedgehog signal transduction at multiple levels

    Institute of Scientific and Technical Information of China (English)

    Gang Ma; Jiang Yu; Yue Xiao; Danny Chan; Bo Gao; Jianxin Hu; Yongxing He

    2011-01-01

    Brachydactyly type A1 (BDA1),the first recorded Mendelian autosomal dominant disorder in humans,is characterized by a shortening or absence of the middle phalanges.Heterozygous missense mutations in the Indian Hedgehog (IHH) gene have been identified as a cause of BDA1; however,the biochemical consequences of these mutations are unclear.In this paper,we analyzed three BDA1 mutations (E95K,D100E,and E131K)in the N-terminal fragment of Indian Hedgehog (IhhN).Structural analysis showed that the E95K mutation changes a negatively charged area to a positively charged area in a calcium-binding groove,and that the D100E mutation changes the local tertiary structure.Furthermore,we showed that the E95K and D100E mutations led to a temperature-sensitive and calcium-dependent instability of lhhN,which might contribute to an enhanced intracellular degradation of the mutant proteins via the lysosome.Notably,all three mutations affected Hh binding to the receptor Patched1 (PTC1),reducing its capacity to induce cellular differentiation.We propose that these are common features of the mutations that cause BDA1,affecting the Hh tertiary structure,intracellular fate,binding to the receptor/partners,and binding to extracellular components.The combination of these features alters signaling capacity and range,but the impact is likely to be variable and mutation-dependent.The potential variation in the signaling range is characterized by an enhanced interaction with heparan sulfate for IHH with the E95K mutation,but not the E131K mutation.Taken together,our results suggest that these IHH mutations affect Hh signaling at multiple levels,causing abnormal bone development and abnormal digit formation.

  2. Thermoelectric material including a multiple transition metal-doped type I clathrate crystal structure

    Science.gov (United States)

    Yang, Jihui; Shi, Xun; Bai, Shengqiang; Zhang, Wenqing; Chen, Lidong; Yang, Jiong

    2012-01-17

    A thermoelectric material includes a multiple transition metal-doped type I clathrate crystal structure having the formula A.sub.8TM.sub.y.sub.1.sup.1TM.sub.y.sub.2.sup.2 . . . TM.sub.y.sub.n.sup.nM.sub.zX.sub.46-y.sub.1.sub.-y.sub.2.sub.- . . . -y.sub.n.sub.-z. In the formula, A is selected from the group consisting of barium, strontium, and europium; X is selected from the group consisting of silicon, germanium, and tin; M is selected from the group consisting of aluminum, gallium, and indium; TM.sup.1, TM.sup.2, and TM.sup.n are independently selected from the group consisting of 3d, 4d, and 5d transition metals; and y.sub.1, y.sub.2, y.sub.n and Z are actual compositions of TM.sup.1, TM.sup.2, TM.sup.n, and M, respectively. The actual compositions are based upon nominal compositions derived from the following equation: z=8q.sub.A-|.DELTA.q.sub.1|y.sub.1-|.DELTA.q.sub.2|y.sub.2- . . . -|.DELTA.q.sub.n|y.sub.n, wherein q.sub.A is a charge state of A, and wherein .DELTA.q.sub.1, .DELTA.q.sub.2, .DELTA.q.sub.n are, respectively, the nominal charge state of the first, second, and n-th TM.

  3. Tailor-made rehabilitation approach using multiple types of hybrid assistive limb robots for acute stroke patients: A pilot study.

    Science.gov (United States)

    Fukuda, Hiroyuki; Morishita, Takashi; Ogata, Toshiyasu; Saita, Kazuya; Hyakutake, Koichi; Watanabe, Junko; Shiota, Etsuji; Inoue, Tooru

    2016-01-01

    This article investigated the feasibility of a tailor-made neurorehabilitation approach using multiple types of hybrid assistive limb (HAL) robots for acute stroke patients. We investigated the clinical outcomes of patients who underwent rehabilitation using the HAL robots. The Brunnstrom stage, Barthel index (BI), and functional independence measure (FIM) were evaluated at baseline and when patients were transferred to a rehabilitation facility. Scores were compared between the multiple-robot rehabilitation and single-robot rehabilitation groups. Nine hemiplegic acute stroke patients (five men and four women; mean age 59.4 ± 12.5 years; four hemorrhagic stroke and five ischemic stroke) underwent rehabilitation using multiple types of HAL robots for 19.4 ± 12.5 days, and 14 patients (six men and eight women; mean age 63.2 ± 13.9 years; nine hemorrhagic stroke and five ischemic stroke) underwent rehabilitation using a single type of HAL robot for 14.9 ± 8.9 days. The multiple-robot rehabilitation group showed significantly better outcomes in the Brunnstrom stage of the upper extremity, BI, and FIM scores. To the best of the authors' knowledge, this is the first pilot study demonstrating the feasibility of rehabilitation using multiple exoskeleton robots. The tailor-made rehabilitation approach may be useful for the treatment of acute stroke.

  4. Coronary Heart Disease Risk between Active and Inactive Women with Multiple Sclerosis.

    Science.gov (United States)

    Slawta, Jennifer N.; McCubbin, Jeffrey A.; Wilcox, Anthony R.; Fox, Susan D.; Nalle, Darek J.; Anderson, Gail

    2002-01-01

    Investigated whether abdominal fat accumulation and levels of triglyceride, high-density lipoprotein cholesterol, and glucose differed between 123 active and inactive women with multiple sclerosis (MS). Results indicated that low-to-moderate leisure time physical activity significantly related to less abdominal fat accumulation, lower triglyceride…

  5. Social Cognitive Correlates of Physical Activity in Inactive Adults with Multiple Sclerosis

    Science.gov (United States)

    Dlugonski, Deirdre; Wojcicki, Thomas R.; McAuley, Edward; Motl, Robert W.

    2011-01-01

    Persons with multiple sclerosis (MS) are often physically inactive. This observation has prompted the search for modifiable constructs derived from established theories that act as correlates of physical activity. This study investigated self efficacy, outcome expectations, impediments, and goal setting as correlates of physical activity in…

  6. Telephone-Based Physical Activity Counseling for Major Depression in People with Multiple Sclerosis

    Science.gov (United States)

    Bombardier, Charles H.; Ehde, Dawn M.; Gibbons, Laura E.; Wadhwani, Roini; Sullivan, Mark D.; Rosenberg, Dori E.; Kraft, George H.

    2013-01-01

    Objective: Physical activity represents a promising treatment for major depressive disorder (MDD) in people with multiple sclerosis (MS). We conducted a single-blind, two-arm randomized controlled trial comparing a 12-week physical activity counseling intervention delivered primarily by telephone (n = 44) to a wait-list control group (N = 48).…

  7. Fibroblast growth factor receptor 3 interacts with and activates TGFβ-activated kinase 1 tyrosine phosphorylation and NFκB signaling in multiple myeloma and bladder cancer.

    Directory of Open Access Journals (Sweden)

    Lisa Salazar

    Full Text Available Cancer is a major public health problem worldwide. In the United States alone, 1 in 4 deaths is due to cancer and for 2013 a total of 1,660,290 new cancer cases and 580,350 cancer-related deaths are projected. Comprehensive profiling of multiple cancer genomes has revealed a highly complex genetic landscape in which a large number of altered genes, varying from tumor to tumor, impact core biological pathways and processes. This has implications for therapeutic targeting of signaling networks in the development of treatments for specific cancers. The NFκB transcription factor is constitutively active in a number of hematologic and solid tumors, and many signaling pathways implicated in cancer are likely connected to NFκB activation. A critical mediator of NFκB activity is TGFβ-activated kinase 1 (TAK1. Here, we identify TAK1 as a novel interacting protein and target of fibroblast growth factor receptor 3 (FGFR3 tyrosine kinase activity. We further demonstrate that activating mutations in FGFR3 associated with both multiple myeloma and bladder cancer can modulate expression of genes that regulate NFκB signaling, and promote both NFκB transcriptional activity and cell adhesion in a manner dependent on TAK1 expression in both cancer cell types. Our findings suggest TAK1 as a potential therapeutic target for FGFR3-associated cancers, and other malignancies in which TAK1 contributes to constitutive NFκB activation.

  8. Three level spinal dysraphism: multiple composite Type 1 and Type 2 split cord malformatıon

    Directory of Open Access Journals (Sweden)

    Alatas I.

    2014-12-01

    Full Text Available It has reported an uncommon case a 3 year-old girl a composite split cord malformation (SCM with two different levels of SCM type1 and one level SCM type2, tight filum and sacral dermal sinus. The patient was admitted with a hypertrichosis and hyperpigmented patch. MRI of whole spine and brain was done. SCM type1 at T 7 and L2 levels and SCM typ2 at T11 level were removed then tight filum was cut and dermal sinus was excised at different sites during the same surge

  9. Cluster Types of Attitudes toward Multiple Role Planning of Single, Korean, Female Undergraduates

    Science.gov (United States)

    Woo, Young Jee; Lee, Ki-Hak

    2010-01-01

    The current study explored the attitudes that single, Korean, female college students have toward multiple role planning. Cluster groups among the participants were identified by their scores on the Korean language version (Yang, 1997) of the Attitudes Toward Multiple Role Planning (ATMRP; Weitzman, 1992) measure, and significant differences in…

  10. EUS is superior for detection of pancreatic lesions compared with standard imaging in patients with multiple endocrine neoplasia type 1

    NARCIS (Netherlands)

    Asselt, S.J. van; Brouwers, A.H.; Dullemen, H.M. van; Jagt, E.J. van der; Bongaerts, A.H.; Kema, I.P.; Koopmans, K.P.; Valk, G.D.; Timmers, H.J.L.M.; Herder, W.W. de; Feelders, R.A.; Fockens, P.; Sluiter, W.J.; Vries, E.G. de; Links, T.P.

    2015-01-01

    BACKGROUND: In multiple endocrine neoplasia type 1 (MEN1), pancreatic neuroendocrine tumors (pNETs) are the leading MEN1-related cause of death. OBJECTIVE: To evaluate EUS and (11)C-5-hydroxytryptophan positron emission tomography ((11)C-5-HTP PET), compared with the recommended screening techniques

  11. Acromegaly in a multiple endocrine neoplasia type 1 (MEN1) family with low penetrance of the disease

    NARCIS (Netherlands)

    Dreijerink, KMA; van Beek, AP; Lentjes, EGWM; Post, JG; van der Luijt, RB; Carnninga-van Dijk, MR; Lips, CJM

    2005-01-01

    Multiple endocrine neoplasia type 1 (MEN1) is an inherited syndrome that is characterised by the occurrence of tumours in the parathyroid glands, the endocrine pancreas, the pituitary gland and the adrenal glands and by neuroendocrine carcinoid tumours, often at a young age. The penetrance of MEN1 a

  12. EUS is superior for detection of pancreatic lesions compared with standard imaging in patients with multiple endocrine neoplasia type 1

    NARCIS (Netherlands)

    van Asselt, Sophie J.; Brouwers, Adrienne H.; van Dullemen, Hendrik M.; van der Jagt, Eric J.; Bongaerts, Alfons H. H.; Kema, Ido P.; Koopmans, Klaas P.; Valk, Gerlof D.; Timmers, Henri J.; de Herder, Wouter W.; Feelders, Richard A.; Fockens, Paul; Sluiter, Wim J.; de Vries, Elisabeth G. E.; Links, Thera P.

    2015-01-01

    Background: In multiple endocrine neoplasia type 1 (MEN1), pancreatic neuroendocrine tumors (pNETs) are the leading MEN1-related cause of death. Objective: To evaluate EUS and C-11-5-hydroxytryptophan positron emission tomography (C-11-5-HTP PET), compared with the recommended screening techniques i

  13. Graphene active plasmonic metamaterials for new types of terahertz lasers

    Science.gov (United States)

    Otsuji, Taiichi; Watanabe, Takayuki; Satou, Akira; Popov, Vyacheslav; Ryzhii, Victor

    2013-05-01

    This paper reviews recent advances in graphene active plasmonic metamaterials for new types of terahertz lasers. We theoretically discovered that when the population of Dirac Fermionic carriers in graphene are inverted by optical or electrical pumping the excitation of graphene plasmons by the THz photons results in propagating surface plasmon polaritons with giant gain in a wide THz range. Furthermore, when graphene is patterned in a micro- or nano-ribbon array by grating gate metallization, the structure acts as an active plasmonic metamaterial, providing a super-radiant plasmonic lasing with giant gain at the plasmon modes in a wide THz frequency range.

  14. Overexpression of N-acetylgalactosamine-4-sulphatase induces a multiple sulphatase deficiency in mucopolysaccharidosis-type-VI fibroblasts.

    Science.gov (United States)

    Anson, D S; Muller, V; Bielicki, J; Harper, G S; Hopwood, J J

    1993-09-15

    High-titre stocks of an amphotropic retrovirus, constructed so as to express a full-length cDNA encoding the human lysosomal enzyme N-acetylgalactosamine-4-sulphatase (4-sulphatase) from the cytomegalovirus immediate early promoter, were used to infect skin fibroblasts from a clinically severe mucopolysaccharidosis type VI (MPS VI) patient. The infected MPS VI cells showed correction of the enzymic defect with the enzyme being expressed at high levels and in the correct subcellular compartment. Surprisingly this did not result in correction of glycosaminoglycan turnover as measured by accumulation of 35S in metabolically labelled cells. We demonstrate that this is apparently caused by an induced reduction of the activities of other lysosomal sulphatases, presumably due to competition for a sulphatase-specific processing mechanism by the over-expressed 4-sulphatase. The level of steroid sulphatase, which is a microsomal sulphatase, was also reduced. Infection of skin fibroblasts from a second, clinically mildly affected, MPS VI patient with the same virus also resulted in no significant change in the level of glycosaminoglycan storage. However, in this case the cause of the observed phenomenon was less clear. These results are of obvious practical importance when considering gene therapy for a sulphatase deficiency such as MPS VI and also provide possible new avenues for exploration of the processes involved in sulphatase synthesis and genetically determined multiple sulphatase deficiency.

  15. Effects of supported metallocene catalyst active center multiplicity on antioxidant-stabilized ethylene homo- and copolymers

    KAUST Repository

    Atiqullah, Muhammad

    2014-10-09

    © 2014 Akadémiai Kiadó, Budapest, Hungary. A silica-supported bis(n-butylcyclopentadienyl) zirconium dichloride [( n BuCp)2ZrCl2] catalyst was synthesized. This was used to prepare an ethylene homopolymer and an ethylene-1-hexene copolymer. The active center multiplicity of this catalyst was modeled by deconvoluting the copolymer molecular mass distribution and chemical composition distribution. Five different active site types were predicted, which matched the successive self-nucleation and annealing temperature peaks. The thermo-oxidative melt stability, with and without Irganox 1010 and Irgafos 168, of the above polyethylenes was investigated using nonisothermal differential scanning calorimetric (DSC) experiments at 150 °C. This is a temperature that ensures complete melting of the samples and avoids the diffusivity of oxygen to interfere into polyethylene crystallinity and its thermo-oxidative melt degradation. The oxidation parameters such as onset oxidation temperature, induction period, protection factor, and S-factor were determined by combining theoretical modeling with the DSC experiments. Subsequently, these findings were discussed considering catalyst active center multiplicity and polymer microstructure, particularly average ethylene sequence length. Several insightful results, which have not been reported earlier in the literature, were obtained. The antioxidant effect, for each polymer, varied as (Irganox + Irgafos) ≈ Irganox > Irgafos > Neat polymer. The as-synthesized homopolymer turned out to be almost twice as stable as the corresponding copolymer. The antioxidant(s) in the copolymer showed higher antioxidant effectiveness (AEX) than those in the homopolymer. Irganox exhibited more AEX than Irgafos. To the best of our knowledge, such findings have not been reported earlier in the literature. However, mixed with Irganox or Irgafos, their melt oxidation stability was comparable. The homopolymer, as per the calculated S-factor, showed Irganox

  16. Soluble Urokinase-Type Plasminogen Activator Receptor Levels in Patients With Schizophrenia

    DEFF Research Database (Denmark)

    Nielsen, Jimmi; Røge, Rasmus; Pristed, Sofie Gry;

    2015-01-01

    BACKGROUND: The etiology of schizophrenia remains largely unknown but alterations in the immune system may be involved. In addition to the psychiatric symptoms, schizophrenia is also associated with up to 20 years reduction in life span. Soluble urokinase-type plasminogen activator receptor (su......PAR) is a protein that can be measured in blood samples and reflects the levels of inflammatory activity. It has been associated with mortality and the development of type 2 diabetes and cardiovascular disease. METHODS: suPAR levels in patients with schizophrenia were compared to healthy controls from the Danish...... Blood Donor Study. SuPAR levels were dichotomized at >4.0 ng/ml, which is considered the threshold for low grade inflammation. A multiple logistic regression model was used and adjusted for age, sex, and current smoking. RESULTS: In total we included 1009 subjects, 105 cases with schizophrenia (10...

  17. Weyl Group Multiple Dirichlet Series Type A Combinatorial Theory (AM-175)

    CERN Document Server

    Brubaker, Ben; Friedberg, Solomon

    2011-01-01

    Weyl group multiple Dirichlet series are generalizations of the Riemann zeta function. Like the Riemann zeta function, they are Dirichlet series with analytic continuation and functional equations, having applications to analytic number theory. By contrast, these Weyl group multiple Dirichlet series may be functions of several complex variables and their groups of functional equations may be arbitrary finite Weyl groups. Furthermore, their coefficients are multiplicative up to roots of unity, generalizing the notion of Euler products. This book proves foundational results about these series an

  18. AMPK activation: a therapeutic target for type 2 diabetes?

    Directory of Open Access Journals (Sweden)

    Coughlan KA

    2014-06-01

    Full Text Available Kimberly A Coughlan, Rudy J Valentine, Neil B Ruderman, Asish K Saha Endocrinology and Diabetes, Department of Medicine, Boston University Medical Center, Boston, MA, USA Abstract: Type 2 diabetes (T2D is a metabolic disease characterized by insulin resistance, β-cell dysfunction, and elevated hepatic glucose output. Over 350 million people worldwide have T2D, and the International Diabetes Federation projects that this number will increase to nearly 600 million by 2035. There is a great need for more effective treatments for maintaining glucose homeostasis and improving insulin sensitivity. AMP-activated protein kinase (AMPK is an evolutionarily conserved serine/threonine kinase whose activation elicits insulin-sensitizing effects, making it an ideal therapeutic target for T2D. AMPK is an energy-sensing enzyme that is activated when cellular energy levels are low, and it signals to stimulate glucose uptake in skeletal muscles, fatty acid oxidation in adipose (and other tissues, and reduces hepatic glucose production. There is substantial evidence suggesting that AMPK is dysregulated in animals and humans with metabolic syndrome or T2D, and that AMPK activation (physiological or pharmacological can improve insulin sensitivity and metabolic health. Numerous pharmacological agents, natural compounds, and hormones are known to activate AMPK, either directly or indirectly – some of which (for example, metformin and thiazolidinediones are currently used to treat T2D. This paper will review the regulation of the AMPK pathway and its role in T2D, some of the known AMPK activators and their mechanisms of action, and the potential for future improvements in targeting AMPK for the treatment of T2D. Keywords: adenosine monophosphate-activated protein kinase, type 2 diabetes, insulin resistance, drug therapy

  19. Molecular evolution of the porcine type I interferon family: subtype-specific expression and antiviral activity.

    Directory of Open Access Journals (Sweden)

    Yongming Sang

    Full Text Available Type I interferons (IFNs, key antiviral cytokines, evolve to adapt with ever-changing viral threats during vertebrate speciation. Due to novel pathogenic pressure associated with Suidae speciation and domestication, porcine IFNs evolutionarily engender both molecular and functional diversification, which have not been well addressed in pigs, an important livestock species and animal model for biomedical sciences. Annotation of current swine genome assembly Sscrofa10.2 reveals 57 functional genes and 16 pseudogenes of type I IFNs. Subfamilies of multiple IFNA, IFNW and porcine-specific IFND genes are separated into four clusters with ∼ 60 kb intervals within the IFNB/IFNE bordered region in SSC1, and each cluster contains mingled subtypes of IFNA, IFNW and IFND. Further curation of the 57 functional IFN genes indicates that they include 18 potential artifactual duplicates. We performed phylogenetic construction as well as analyses of gene duplication/conversion and natural selection and showed that porcine type I IFN genes have been undergoing active diversification through both gene duplication and conversion. Extensive analyses of the non-coding sequences proximal to all IFN coding regions identified several genomic repetitive elements significantly associated with different IFN subtypes. Family-wide studies further revealed their molecular diversity with respect to differential expression and restrictive activity on the resurgence of a porcine endogenous retrovirus. Based on predicted 3-D structures of representative animal IFNs and inferred activity, we categorized the general functional propensity underlying the structure-activity relationship. Evidence indicates gene expansion of porcine type I IFNs. Genomic repetitive elements that associated with IFN subtypes may serve as molecular signatures of respective IFN subtypes and genomic mechanisms to mediate IFN gene evolution and expression. In summary, the porcine type I IFN profile has

  20. An innovative cascade system for simultaneous separation of multiple cell types.

    Directory of Open Access Journals (Sweden)

    Arkadiusz Pierzchalski

    Full Text Available Isolation of different cell types from one sample by fluorescence activated cell sorting is standard but expensive and time consuming. Magnetic separation is more cost effective and faster by but requires substantial effort. An innovative pluriBead-cascade cell isolation system (pluriSelect GmbH, Leipzig, Germany simultaneously separates two or more different cell types. It is based on antibody-mediated binding of cells to beads of different size and their isolation with sieves of different mesh-size. For the first time, we validated the pluriSelect system for simultaneous separation of CD4+- and CD8+-cells from human EDTA-blood samples. Results were compared with those obtained by magnetic activated cell sorting (MACS; two steps -first isolation of CD4+, then restaining of the residual cell suspension with anti-human CD8+ MACS antibody followed by the second isolation. pluriSelect separation was done in whole blood, MACS separation on density gradient isolated mononuclear cells. Isolated and residual cells were immunophenotyped by 7-color 9-marker panel (CD3; CD16/56; CD4; CD8; CD14; CD19; CD45; HLA-DR using flow cytometry. Cell count, purity, yield and viability (7-AAD exclusion were determined. There were no significant differences between both systems regarding purity (MACS (median[range]: 92.4% [91.5-94.9] vs. pluriSelect 95% [94.9-96.8] of CD4+ cells, however CD8+ isolation showed lower purity by MACS (74.8% [67.6-77.9], pluriSelect 89.9% [89.0-95.7]. Yield was not significantly different for CD4 (MACS 58.5% [54.1-67.5], pluriSelect 67.9% [56.8-69.8] and for CD8 (MACS 57.2% [41.3-72.0], pluriSelect 67.2% [60.0-78.5]. Viability was slightly higher with MACS for CD4+ (98.4% [97.8-99.0], pluriSelect 94.1% [92.1-95.2] and for CD8+-cells (98.8% [98.3-99.1], pluriSelect 86.7% [84.2-89.9]. pluriSelect separation was substantially faster than MACS (1h vs. 2.5h and no pre-enrichment steps were necessary. In conclusion, pluriSelect is a fast, simple

  1. Multiple contexts of exposure: Activity spaces, residential neighborhoods, and self-rated health.

    Science.gov (United States)

    Sharp, Gregory; Denney, Justin T; Kimbro, Rachel T

    2015-12-01

    Although health researchers have made progress in detecting place effects on health, existing work has largely focused on the local residential neighborhood and has lacked a temporal dimension. Little research has integrated both time and space to understand how exposure to multiple contexts - where adults live, work, shop, worship, and seek healthcare - influence and shape health and well-being. This study uses novel longitudinal data from the Los Angeles Family and Neighborhood Survey to delve deeper into the relationship between context and health by considering residential and activity space neighborhoods weighted by the amount of time spent in these contexts. Results from multilevel cross-classified logistic models indicate that contextual exposure to disadvantage, residential or non-residential, is independently associated with a higher likelihood of reporting poor or fair health. We also find support for a contextual incongruence hypothesis. For example, adults living in the most disadvantaged neighborhoods are more likely to report poor or fair health when they spend time in more advantaged neighborhoods than in more disadvantaged ones, while residents of more advantaged neighborhoods report worse health when they spend time in more disadvantaged areas. Our results suggest that certain types of place-based cumulative exposures are associated with a sense of relative neighborhood deprivation that potentially manifests in worse health ratings.

  2. Functioning glucagonoma associated with primary hyperparathyroidism: multiple endocrine neoplasia type 1 or incidental association?

    Directory of Open Access Journals (Sweden)

    Erdas Enrico

    2012-12-01

    Full Text Available Abstract Background Diagnosis of multiple endocrine neoplasia type 1 (MEN1 is commonly based on clinical criteria, and confirmed by genetic testing. In patients without known MEN1-related germline mutations, the possibility of a casual association between two or more endocrine tumors cannot be excluded and subsequent management may be difficult to plan. We describe a very uncommon case of functioning glucagonoma associated with primary hyperparathyroidism (pHPT in which genetic testing failed to detect germline mutations of MEN-1 and other known genes responsible for MEN1. Case presentation The patient, a 65-year old woman, had been suffering for more than 1 year from weakness, progressive weight loss, angular cheilitis, glossitis and, more recently, skin rashes on the perineum, perioral skin and groin folds. After multidisciplinary investigations, functioning glucagonoma and asymptomatic pHPT were diagnosed and, since family history was negative, sporadic MEN1 was suspected. However, genetic testing revealed neither MEN-1 nor other gene mutations responsible for rarer cases of MEN1 (CDKN1B/p27 and other cyclin-dependent kinase inhibitor genes CDKN1A/p15, CDKN2C/p18, CDKN2B/p21. The patient underwent distal splenopancreatectomy and at the 4-month follow-up she showed complete remission of symptoms. Six months later, a thyroid nodule, suspected to be a malignant neoplasia, and two hyperfunctioning parathyroid glands were detected respectively by ultrasound with fine needle aspiration cytology and 99mTc-sestamibi scan with SPECT acquisition. Total thyroidectomy was performed, whereas selective parathyroidectomy was preferred to a more extensive procedure because the diagnosis of MEN1 was not supported by genetic analysis and intraoperative intact parathyroid hormone had revealed “adenoma-like” kinetics after the second parathyroid resection. Thirty-nine and 25 months after respectively the first and the second operation, the patient is well

  3. Understanding Activity Cycles of Solar Type Stars with Kepler

    Science.gov (United States)

    Tovar, Guadalupe; Montet, Benjamin; Johnson, John A.

    2017-01-01

    As the era of exploring new worlds and systems advances we seek to answer the question: How common is our Sun? There is considerable evidence about the recurring activity cycles of our Sun but very little is known about the activity cycles of other stars. By calibrating the full frame images from the original Kepler mission that were taken once a month over the course of four years, we are able to do relative photometry on roughly 5 million stars. By building a model of the pixel response function we were able to achieve 0.8% precision photometry. We identify 50,000 solar type stars based on magnitude, surface gravity, and temperature cuts. We observe the relative increase and decrease in brightness of the stars indicating signs of activity cycles similar to our Sun. We continue to explore how a data driven pixel response function model could improve our precision to 0.1% photometry measurements.

  4. Ecosystem services capacity across heterogeneous forest types: understanding the interactions and suggesting pathways for sustaining multiple ecosystem services.

    Science.gov (United States)

    Alamgir, Mohammed; Turton, Stephen M; Macgregor, Colin J; Pert, Petina L

    2016-10-01

    As ecosystem services supply from tropical forests is declining due to deforestation and forest degradation, much effort is essential to sustain ecosystem services supply from tropical forested landscapes, because tropical forests provide the largest flow of multiple ecosystem services among the terrestrial ecosystems. In order to sustain multiple ecosystem services, understanding ecosystem services capacity across heterogeneous forest types and identifying certain ecosystem services that could be managed to leverage positive effects across the wider bundle of ecosystem services are required. We sampled three forest types, tropical rainforests, sclerophyll forests, and rehabilitated plantation forests, over an area of 32,000m(2) from Wet Tropics bioregion, Australia, aiming to compare supply and evaluate interactions and patterns of eight ecosystem services (global climate regulation, air quality regulation, erosion regulation, nutrient regulation, cyclone protection, habitat provision, energy provision, and timber provision). On average, multiple ecosystem services were highest in the rainforests, lowest in sclerophyll forests, and intermediate in rehabilitated plantation forests. However, a wide variation was apparent among the plots across the three forest types. Global climate regulation service had a synergistic impact on the supply of multiple ecosystem services, while nutrient regulation service was found to have a trade-off impact. Considering multiple ecosystem services, most of the rehabilitated plantation forest plots shared the same ordination space with rainforest plots in the ordination analysis, indicating that rehabilitated plantation forests may supply certain ecosystem services nearly equivalent to rainforests. Two synergy groups and one trade-off group were identified. Apart from conserving rainforests and sclerophyll forests, our findings suggest two additional integrated pathways to sustain the supply of multiple ecosystem services from a

  5. AMPK activation: a therapeutic target for type 2 diabetes?

    Science.gov (United States)

    Coughlan, Kimberly A; Valentine, Rudy J; Ruderman, Neil B; Saha, Asish K

    2014-01-01

    Type 2 diabetes (T2D) is a metabolic disease characterized by insulin resistance, β-cell dysfunction, and elevated hepatic glucose output. Over 350 million people worldwide have T2D, and the International Diabetes Federation projects that this number will increase to nearly 600 million by 2035. There is a great need for more effective treatments for maintaining glucose homeostasis and improving insulin sensitivity. AMP-activated protein kinase (AMPK) is an evolutionarily conserved serine/threonine kinase whose activation elicits insulin-sensitizing effects, making it an ideal therapeutic target for T2D. AMPK is an energy-sensing enzyme that is activated when cellular energy levels are low, and it signals to stimulate glucose uptake in skeletal muscles, fatty acid oxidation in adipose (and other) tissues, and reduces hepatic glucose production. There is substantial evidence suggesting that AMPK is dysregulated in animals and humans with metabolic syndrome or T2D, and that AMPK activation (physiological or pharmacological) can improve insulin sensitivity and metabolic health. Numerous pharmacological agents, natural compounds, and hormones are known to activate AMPK, either directly or indirectly - some of which (for example, metformin and thiazolidinediones) are currently used to treat T2D. This paper will review the regulation of the AMPK pathway and its role in T2D, some of the known AMPK activators and their mechanisms of action, and the potential for future improvements in targeting AMPK for the treatment of T2D.

  6. Hepatobiliary fascioliasis with multiple aneurysms and active bleeding: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Soo Young; Kim Jae Woon; Jang, Jae Cheon [Dept. of Radiology, College of Medicine, Yeungnam University, Daegu (Korea, Republic of)

    2015-04-15

    A 52-year-old woman visited our institution with upper abdominal pain which had lasted for the past two days. Laboratory tests revealed mild leukocytosis, decreased serum hemoglobin, and peripheral blood eosinophilia. CT scans showed multiple ill-defined, hypodense lesions in the peripheral areas of both hepatic lobes and active bleeding with a subcapsular hematoma in the right hepatic lobe. Angiography also showed active bleeding in the right hepatic lobe with multiple aneurysms, so a transarterial coil embolization was performed to stop the bleeding. The endoscopic retrograde cholangiopancreatography revealed several moving flat flukes in the common bile duct, which were pathologically confirmed as Fasciola hepatica.

  7. The different neighbours around Type-1 and Type-2 active galactic nuclei

    CERN Document Server

    Villarroel, Beatriz

    2014-01-01

    One of the most intriguing open issues in galaxy evolution is the structure and evolution of active galactic nuclei (AGN) that emit intense light believed to come from an accretion disk near a super-massive black hole (Rees 1984, Lynden-Bell 1969). To understand the zoo of different AGN classes, it has been suggested that all AGN are the same type of object viewed from different angles (Antonucci 1993). This model -- called AGN unification -- has been successful in predicting e.g. the existence of hidden broad optical lines in the spectrum of many narrow-line AGN. But this model is not unchallenged (Tran 2001) and it is an open problem whether more than viewing angle separates the so-called Type-1 and Type-2 AGN. Here we report the first large-scale study that finds strong differences in the galaxy neighbours to Type-1 and Type-2 AGN with data from the Sloan Digital Sky Survey (SDSS) (York et al. 2000) Data Release 7 (DR7) (Abazajian et al. 2008) and Galaxy Zoo (Lintott et al, 2008, Lintott et al 2011). We fi...

  8. Diabetic gangrene in multiple fingers and toes after a dog bite in an elderly patient with type 2 diabetes.

    Science.gov (United States)

    Oya, Junko; Hanai, Ko; Miura, Junnosuke; Maruyama, Satoko; Ishii, Akiko; Syono, Kazu; Shinjo, Takamichi; Iwamoto, Yasuhiko

    2011-01-01

    A 78-year-old diabetic woman experienced multiple sites of gangrene not only in fingers that were directly bitten by a dog but also in fingers and toes that had not beenbitten. Her glycemic control was fair and microvascular complications were mild. There were no clinical findings related to angitis, collagenosis or severe infection. The fingers and toes with gangrene were amputated. The pathological diagnosis was diabetic gangrene. This report presents a case of multiple sites of gangrene of the fingers and toes after a dog bite in an elderly patient with type 2 diabetes.

  9. Transgenic chickens expressing human urokinase-type plasminogen activator.

    Science.gov (United States)

    Lee, Sung Ho; Gupta, Mukesh Kumar; Ho, Young Tae; Kim, Teoan; Lee, Hoon Taek

    2013-09-01

    Urokinase-type plasminogen activator is a serine protease that is clinically used in humans for the treatment of thrombolytic disorders and vascular diseases such as acute ischemic stroke and acute peripheral arterial occlusion. This study explored the feasibility of using chickens as a bioreactor for producing human urokinase-type plasminogen activator (huPA). Recombinant huPA gene, under the control of a ubiquitous Rous sarcoma virus promoter, was injected into the subgerminal cavity of freshly laid chicken eggs at stage X using the replication-defective Moloney murine leukemia virus (MoMLV)-based retrovirus vectors encapsidated with VSV-G (vesicular stomatitis virus G) glycoprotein. A total of 38 chicks, out of 573 virus-injected eggs, hatched and contained the huPA gene in their various body parts. The mRNA transcript of the huPA gene was present in various organs, including blood and egg, and was germ-line transmitted to the next generation. The level of active huPA protein was 16-fold higher in the blood of the transgenic chicken than in the nontransgenic chicken (P pharming of the huPA drug but also be useful for studying huPA-induced bleeding and other disorders.

  10. EUV Flare Activity in Late-Type Stars

    CERN Document Server

    Audard, M; Drake, J J; Kashyap, V L; Audard, Marc; Guedel, Manuel; Drake, Jeremy J.

    2000-01-01

    \\textit{Extreme Ultraviolet Explorer} Deep Survey observations of cool stars (spectral type F to M) have been used to investigate the distribution of coronal flare rates in energy and its relation to activity indicators and rotation parameters. Cumulative and differential flare rate distributions were constructed and fitted with different methods. Power laws are found to approximately describe the distributions. A trend toward flatter distributions for later-type stars is suggested in our sample. Assuming that the power laws continue below the detection limit, we have estimated that the superposition of flares with radiated energies of about $10^{29}-10^{31}$ergs could explain the observed radiative power loss of these coronae, while the detected flares are contributing only $\\approx 10$%. While the power-law index is not correlated with rotation parameters (rotation period, projected rotational velocity, Rossby number) and only marginally with the X-ray luminosity, the flare occurrence rate is correlated wit...

  11. Activities of daily living and lesion position among multiple sclerosis patients by Bayes network

    Institute of Scientific and Technical Information of China (English)

    Zhifang Pan; Hongtao Lu; Qi Cheng

    2013-01-01

    Magnetic resonance imaging is a highly sensitive approach for diagnosis of multiple sclerosis, and T2-weighted images can reveal lesions in the cerebral white matter, gray matter, and spinal cord. However, the lesions have a poor correlation with measurable clinical disability. In this study, we performed a large-scale epidemiological survey of 238 patients with multiple sclerosis in eleven districts by network member hospitals in Shanghai, China within 1 year. The involved patients were scanned for position and size of lesions by MRI. Results showed that lesions in the cerebrum, spinal cord, or supratentorial position had an impact on the activities of daily living in multiple sclerosis patients, as assessed by the Bayes network. On the other hand, brainstem lesions were very unlikely to influence the activities of daily living, and were not associated with the position of lesion, patient's gender, and patient's living place.

  12. Charcot-Marie-Tooth syndrome and neurofibromatosis type 1 with multiple neurofibromas of the entire spinal nerve roots.

    Science.gov (United States)

    Onu, David O; Hunn, Andrew W; Peters-Willke, Jens

    2013-07-13

    The coexistence of polyneuropathy which has the definite clinical and electromyographical findings consistent with Charcot-Marie-Tooth (CMT) syndrome and neurofibromatosis type 1 (NF1) has infrequently been reported. We describe a patient with both CMT and NF1, who had multiple neurofibromas involving the entire spinal neural axis. In addition, he had multiple neurofibromas distributed within the ileopsoas and gluteus muscles and subcutaneous tissues. These lesions were detected readily by MRI and the patient underwent successful surgical resection of the largest tumours compressing bilateral C2 nerve roots. To our knowledge, this is the first reported case of CMT syndrome coexisting with NF1 in which multiple neurofibromas involved the entire spinal nerve roots. We discuss the diagnostic and therapeutic challenges, emphasising the role of MRI and electrophysiology in such cases and provide a literature review.

  13. Causes of Death and Prognostic Factors in Multiple Endocrine Neoplasia Type 1: A Prospective Study

    Science.gov (United States)

    Ito, Tetsuhide; Igarashi, Hisato; Uehara, Hirotsugu; Berna, Marc J.; Jensen, Robert T.

    2013-01-01

    Abstract Multiple endocrine neoplasia type 1 (MEN1) is classically characterized by the development of functional or nonfunctional hyperplasia or tumors in endocrine tissues (parathyroid, pancreas, pituitary, adrenal). Because effective treatments have been developed for the hormone excess state, which was a major cause of death in these patients in the past, coupled with the recognition that nonendocrine tumors increasingly develop late in the disease course, the natural history of the disease has changed. An understanding of the current causes of death is important to tailor treatment for these patients and to help identify prognostic factors; however, it is generally lacking. To add to our understanding, we conducted a detailed analysis of the causes of death and prognostic factors from a prospective long-term National Institutes of Health (NIH) study of 106 MEN1 patients with pancreatic endocrine tumors with Zollinger-Ellison syndrome (MEN1/ZES patients) and compared our results to those from the pooled literature data of 227 patients with MEN1 with pancreatic endocrine tumors (MEN1/PET patients) reported in case reports or small series, and to 1386 patients reported in large MEN1 literature series. In the NIH series over a mean follow-up of 24.5 years, 24 (23%) patients died (14 MEN1-related and 10 non-MEN1-related deaths). Comparing the causes of death with the results from the 227 patients in the pooled literature series, we found that no patients died of acute complications due to acid hypersecretion, and 8%–14% died of other hormone excess causes, which is similar to the results in 10 large MEN1 literature series published since 1995. In the 2 series (the NIH and pooled literature series), two-thirds of patients died from an MEN1-related cause and one-third from a non-MEN1-related cause, which agrees with the mean values reported in 10 large MEN1 series in the literature, although in the literature the causes of death varied widely. In the NIH and pooled

  14. Active Learning and Threshold Concepts in Multiple Testing That Can Further Develop Student Critical Statistical Thinking

    Science.gov (United States)

    White, Desley

    2015-01-01

    Two practical activities are described, which aim to support critical thinking about statistics as they concern multiple outcomes testing. Formulae are presented in Microsoft Excel spreadsheets, which are used to calculate the inflation of error associated with the quantity of tests performed. This is followed by a decision-making exercise, where…

  15. Effects of Multiple Intelligences Activities on Writing Skill Development in an EFL Context

    Science.gov (United States)

    Gündüz, Zennure Elgün; Ünal, Ismail Dogan

    2016-01-01

    This study aims at exploring the effects of multiple intelligences activities versus traditional method on English writing development of the sixth grade students in Turkey. A quasi-experimental research method with a pre-test post-test design was applied. The participants were 50 sixth grade students at a state school in Ardahan in Turkey. The…

  16. Peptidylarginine deiminase activity in postmortem white matter of patients with multiple sclerosis

    NARCIS (Netherlands)

    De Keyser, J; Schaaf, M; Teelken, A

    1999-01-01

    The myelin sheath in multiple sclerosis (MS) appears to contain a higher proportion of the citrullinated isoform of myelin basic protein MBP-C8. In vitro, MBP-associated arginine is deiminated to citrulline by the enzyme peptidylarginine deiminase (PAD). We investigated PAD activity in white matter

  17. Proteinase-activated receptor 2 modulates neuroinflammation in experimental autoimmune encephalomyelitis and multiple sclerosis

    NARCIS (Netherlands)

    F. Noorbakhsh (Farshid); K. Tsutsui (Kazuyoshi); N. Vergnolle (Nathalie); L.A. Boven (Leonie); S.F. Shariat (Shahrokh); M. Vodjgani (Mohammed); K.G. Warren (Kenneth); P. Andrade-Gordon (Patricia); N.K. Hollenberg (Norman); C. Power (Christopher)

    2006-01-01

    textabstractThe proteinase-activated receptors (PARs) are widely recognized for their modulatory properties of inflammation and neurodegeneration. We investigated the role of PAR2 in the pathogenesis of multiple sclerosis (MS) in humans and experimental autoimmune encephalomyelitis (EAE) in mice. PA

  18. Surveying the Bright Stars by Optical Interferometry I: A Search for Multiplicity Among Stars of Spectral Types F - K

    CERN Document Server

    Hutter, Donald; Tycner, Christopher; Benson, James; Hummel, Christian; Sanborn, Jason; Franz, Otto G; Johnston, Kenneth

    2016-01-01

    We present the first results from an ongoing survey for multiplicity among the bright stars using the Navy Precision Optical Interferometer (NPOI). We first present a summary of NPOI observations of known multiple systems, including the first detection of the companion of $\\beta$ Scuti with precise relative astrometry, to illustrate the instrument's detection sensitivity for binaries at magnitude differences $\\Delta$$m$ $\\lessapprox$ 3 over the range of angular separation 3 - 860 milliarcseconds (mas). A limiting $\\Delta$$m_{700}$ $\\sim$ 3.5 is likely for binaries where the component spectral types differ by less than two. Model fits to these data show good agreement with published orbits, and we additionally present a new orbit solution for one of these stars, $\\sigma$ Her. We then discuss early results of the survey of bright stars at $\\delta$ $\\geq$ -20$\\deg$. This survey, which complements previous surveys of the bright stars by speckle interferometry, initially emphasizes bright stars of spectral types F...

  19. HLA typing in acute optic neuritis. Relation to multiple sclerosis and magnetic resonance imaging findings

    DEFF Research Database (Denmark)

    Frederiksen, J.L.; Madsen, H.O.; Ryder, L.P.;

    1997-01-01

    OBJECTIVE: To study the association of brain magnetic resonance imaging (MRI) findings and HLA findings to clarify the relationship between monosymptomatic optic neuritis (ON) and ON as part of clinically definite multiple sclerosis (CDMS). DESIGN: Population-based cohort of patients with ON refe...

  20. Bone marrow lambda-type light chain crystalline structures associated with multiple myeloma.

    Science.gov (United States)

    Schvartz, H; Bonhomme, P; Caulet, S; Beorchia, A; Patey, M; Caulet, T

    1985-01-01

    A 58-year-old man showed bone marrow crystalline structures associated with a lambda light chain producing multiple myeloma. Analysis and processing of electron images clearly displayed the periodic structure of the crystals. Immunochemistry suggested that they contained the whole or a fragmented constant portion of immunoglobulin.

  1. The Representation of Multiple Intelligences Types in the Top-Notch Series: A Textbook Evaluation

    Science.gov (United States)

    Razmjoo, Seyyed Ayatollah; Jozaghi, Zahra

    2010-01-01

    This study aims at evaluating Top-Notch series through a checklist devised by the researchers based on the elements of the Multiple Intelligences (MI) theory proposed by Gardner (1998). With the shift from teacher-centered classrooms to learner-centered one, more and more research is needed to be done in the realm of students' need analysis. One…

  2. Frank Aggregation Operators for Triangular Interval Type-2 Fuzzy Set and Its Application in Multiple Attribute Group Decision Making

    Directory of Open Access Journals (Sweden)

    Jindong Qin

    2014-01-01

    Full Text Available This paper investigates an approach to multiple attribute group decision-making (MAGDM problems, in which the individual assessments are in the form of triangle interval type-2 fuzzy numbers (TIT2FNs. Firstly, some Frank operation laws of triangle interval type-2 fuzzy set (TIT2FS are defined. Secondly, some Frank aggregation operators such as the triangle interval type-2 fuzzy Frank weighted averaging (TIT2FFWA operator and the triangle interval type-2 fuzzy Frank weighted geometric (TIT2FFWG operator are developed for aggregation TIT2FNs. Furthermore, some desirable properties of the two aggregation operators are analyzed in detail. Finally, an approach based on TIT2FFWA (or TIT2FFWG operator to solve MAGDM is developed. An illustrative example about supplier selection is provided to illustrate the developed procedures. The results demonstrate the practicality and effectiveness of our new method.

  3. Detectability, Observability and Lyapunov-Type Theorems of Linear Discrete Time-Varying Stochastic Systems with Multiplicative Noise

    OpenAIRE

    2015-01-01

    The objective of this paper is to study detectability, observability and related Lyapunov-type theorems of linear discrete-time time-varying stochastic systems with multiplicative noise. Some new concepts such as uniform detectability, ${\\cal K}^{\\infty}$-exact detectability (resp. ${\\cal K}^{WFT}$-exact detectability, ${\\cal K}^{FT}$-exact detectability, ${\\cal K}^{N}$-exact detectability) and ${\\cal K}^{\\infty}$-exact observability (resp. ${\\cal K}^{WFT}$-exact observability, ${\\cal K}^{FT}...

  4. Sonographic Findings of Medullary Thyroid Carcinoma Leading to Diagnosis of Multiple Endocrine Neoplasia Type 2a during Pregnancy

    Directory of Open Access Journals (Sweden)

    David M. Sherer

    2011-09-01

    Full Text Available Multiple endocrine neoplasia (MEN type 2a (Sipple's syndrome is characterized by medullary thyroid carcinoma and pheochromocytoma, and in a smaller percentage of cases, multiglandular parathyroid hyperplasia. This autosomal-dominant syndrome is due to a mutation in the rearranged during transfection (RET proto-oncogene located on chromosome 10cen–10q11.2 and rarely complicates pregnancy. We present an unusual case in a patient with an enlarged thyroid with sonographic findings characteristic of thyroid cancer, which led to diagnosis and subsequent management of RET proto-oncogene-positive MEN type 2a complicating pregnancy.

  5. Endovascular repair of multiple infrageniculate aneurysms in a patient with vascular type Ehlers-Danlos syndrome.

    Science.gov (United States)

    Domenick, Natalie; Cho, Jae S; Abu Hamad, Ghassan; Makaroun, Michel S; Chaer, Rabih A

    2011-09-01

    Patients with vascular type Ehler-Danlos syndrome can develop aneurysms in unusual locations. We describe the case of a 33-year-old woman with vascular type Ehlers-Danlos syndrome who developed metachronous tibial artery aneurysms that were sequentially treated with endovascular means.

  6. Microstructures and Hardness of 8CrWMoV Steel with Multiple Types of Ultra Fine Carbides

    Institute of Scientific and Technical Information of China (English)

    DAI Yu-mei; ZHANG Zhan-ping; MA Yong-qing; QI Yu-hong; LIU Yan-xia; YU Tao

    2004-01-01

    The structure and hardness of 8CrWMoV steel with multiple types of ultra fine carbides are studied after annealing, quenching and tempering in this paper. The results show that multiple types of carbides M3C, M7C3, M23C6, M6C and MC were observed in the annealed steel. Nucleation and coalescence of new carbides, partial dissolution of original carbides in γ phase region during annealing at 800~840℃, result in ultra-fine carbides. Average size of the carbides is0.33~0.34μm in the steel annealed at 800~840℃. Because M3C and M23C6 dissolve easily in austenite, the high hardness HRC63~65 can be obtained by quenching at 840~860℃. Un-dissolved carbides M6C and MC (VC) can effectively prevent the coarsening of austenitic grain, and conduce to obtain very fine martensite. The retained austenite can be easy to decompose during tempering at low and middle temperature due to the precipitation of multiple types of carbides and the good tempering-resistance of the steel is obtained. The microstructure and property of the steel after heat treatment can be accurately explained by calculating based on phase equilibrium thermodynamic.Key Words: 8CrWMoV steel, ultra-fine carbide, heat treatment, microstructure, hardness

  7. Cooperative task assignment of multiple heterogeneous unmanned aerial vehicles using a modified genetic algorithm with multi-type genes

    Institute of Scientific and Technical Information of China (English)

    Deng Qibo; Yu Jianqiao; Wang Ningfei

    2013-01-01

    The task assignment problem of multiple heterogeneous unmanned aerial vehicles (UAVs), concerned with cooperative decision making and control, is studied in this paper. The heterogeneous vehicles have different operational capabilities and kinematic constraints, and carry limited resources (e.g., weapons) onboard. They are designated to perform multiple consecutive tasks cooperatively on multiple ground targets. The problem becomes much more complicated because of these terms of heterogeneity. In order to tackle the challenge, we modify the former genetic algorithm with multi-type genes to stochastically search a best solution. Genes of chromo-somes are different, and they are assorted into several types according to the tasks that must be performed on targets. Different types of genes are processed specifically in the improved genetic operators including initialization, crossover, and mutation. We also present a mirror representation of vehicles to deal with the limited resource constraint. Feasible chromosomes that vehicles could perform tasks using their limited resources under the assignment are created and evolved by genetic operators. The effect of the proposed algorithm is demonstrated in numerical simulations. The results show that it effectively provides good feasible solutions and finds an optimal one.

  8. Identification of multiple HPV types on spermatozoa from human sperm donors

    DEFF Research Database (Denmark)

    Kaspersen, Maja D; Larsen, Peter B; Ingerslev, Hans Jakob

    2011-01-01

    Human papillomaviruses (HPV) may cause sexually transmitted disease. High-risk types of HPV are involved in the development of cervical cell dysplasia, whereas low-risk types may cause genital condyloma. Despite the association between HPV and cancer, donor sperm need not be tested for HPV...... contain HPV, most of them of high-risk types binding to the equatorial segment of the sperm cell. Most HPV-positive sperm showed decreased staining with DAPI, indicative of reduced content of DNA. Our data demonstrate that oncogenic HPV types are frequent in men....... according to European regulations. Consequently, the potential health risk of HPV transmission by donor bank sperm has not been elucidated, nor is it known how HPV is associated with sperm. The presence of 35 types of HPV was examined on DNA from semen samples of 188 Danish sperm donors using a sensitive...

  9. Dynamic activity of NF-κB in multiple trauma patients and protective effects of ulinastain

    Directory of Open Access Journals (Sweden)

    LI Jun

    2012-02-01

    Full Text Available 【Abstract】Objective: To investigate the dynamic activity of NF-κB at the early stage of injury in multiple trauma patients and the protective effects of ulinastain. Methods: From January 2008 to May 2010, patients with multiple traumas admitted to our emergency department were enrolled in this study. Their age varied from 20-55 years. All enrolled patients were assigned randomly into control group (26 cases of multiple injury without ulinastain treatment, ulinastain group (25 cases of multiple injury with ulinastain treatment, and mild injury group (20 cases for basic control. The inclusion criteria for mild injury group were AIS-2005≤3, single wound, previously healthy inhospital patients without the history of surgical intervention. In addition to routine treatment, patients in ulinastain group were intravenously injected 200 000 IU of ulinastain dissolved in 100 ml of normal saline within 12 hours after injury and subsequently injected at the interval of every 8 hours for 7 days. NF-κB activity in monocytes and the level of TNF? IL-1, IL? in serum on admission (day 0, day 1, 2, 3, 4, and 7 were measured. Data were compared and analyzed between different groups. Results: NF-κB activity in monocytes and TNF? IL-1 and IL? of these patients reached peak levels at 24 hour after trauma, with gradual decrease to normal at 72 hour after trauma. NF-κB activity and levels of TNF? IL-1 and IL? were lower in ulinastain group than control one, without any significant difference between the two groups. The mean duration for systemic inflammatory response syndrome and multiple organ dysfunction syndrome was 7 d?.1 d and 10 d?.5 d in ulinastain group and control group respectively, and showed a significant difference. Conclusions: NF-κB activity in monocytes and the levels of inflammatory cytokines in multiply injured patients increased transiently at the early stage of trauma. Ulinastain may shorten the duration of systemic inflammatory

  10. Systematic determination of replication activity type highlights interconnections between replication, chromatin structure and nuclear localization.

    Directory of Open Access Journals (Sweden)

    Shlomit Farkash-Amar

    Full Text Available DNA replication is a highly regulated process, with each genomic locus replicating at a distinct time of replication (ToR. Advances in ToR measurement technology enabled several genome-wide profiling studies that revealed tight associations between ToR and general genomic features and a remarkable ToR conservation in mammals. Genome wide studies further showed that at the hundreds kb-to-megabase scale the genome can be divided into constant ToR regions (CTRs in which the replication process propagates at a faster pace due to the activation of multiple origins and temporal transition regions (TTRs in which the replication process propagates at a slower pace. We developed a computational tool that assigns a ToR to every measured locus and determines its replication activity type (CTR versus TTR. Our algorithm, ARTO (Analysis of Replication Timing and Organization, uses signal processing methods to fit a constant piece-wise linear curve to the measured raw data. We tested our algorithm and provide performance and usability results. A Matlab implementation of ARTO is available at http://bioinfo.cs.technion.ac.il/people/zohar/ARTO/. Applying our algorithm to ToR data measured in multiple mouse and human samples allowed precise genome-wide ToR determination and replication activity type characterization. Analysis of the results highlighted the plasticity of the replication program. For example, we observed significant ToR differences in 10-25% of the genome when comparing different tissue types. Our analyses also provide evidence for activity type differences in up to 30% of the probes. Integration of the ToR data with multiple aspects of chromosome organization characteristics suggests that ToR plays a role in shaping the regional chromatin structure. Namely, repressive chromatin marks, are associated with late ToR both in TTRs and CTRs. Finally, characterization of the differences between TTRs and CTRs, with matching ToR, revealed that TTRs are

  11. Study of TiC+TiN Multiple Films On Type of 316L Stainless Steel

    Institute of Scientific and Technical Information of China (English)

    XUEQi; JINYong; HUDong-ping; HUANGBen-sheng; DENGBai-quan

    2004-01-01

    In this paper, the synthesis process of TiC+TiN multiple films on super-low-carbon stainless steels is reported. The TiC layer is coated as the first layer in the multiple film, the change of growth rate of the film on the 316L Stainlesss teel is not same as the one on carbides substrates, while the mole ratio of CH4 to TiCl4 (mCH4/TiCl4) is changed from 1.2 to 2.0. The Ti [C,N], as a kind of inter-layer between TiC and TiN layers, is helpful to improve the adhesion hetween the TiC and TiN layer. The cooling rate greatly influences the quality of the adhesion between the TiC+TiN film and substrates.

  12. Study of TiC+TiN Multiple Films On Type of 316L Stainless Steel

    Institute of Scientific and Technical Information of China (English)

    XUE Qi; JIN Yong; HU Dong-ping; HUANG Ben-sheng; DENG Bai-quan

    2004-01-01

    In this paper, the synthesis process of TiC+TiN multiple films on super-low-carbon stainless steels is reported.The TiC layer is coated as the first layer in the multiple film, the change of growth rate of the film on the 316L Stainless steel is not same as the one on carbides substrates, while the mole ratio of CH4 to TiCl4 (mCH4/TiCl4) is changed from 1.2to 2.0. The Ti [C, N], as a kind of inter-layer between TiC and TiN layers, is helpful to improve the adhesion between the TiC and TiN layer. The cooling rate greatly influences the quality of the adhesion between the TiC+TiN film and substrates.

  13. Multiple solutions of stick and separation type in the Signorini model with Coulomb friction

    Energy Technology Data Exchange (ETDEWEB)

    Hild, P. [Univ. de Franche-Comte, 25 - Besancon (France). Lab. de Mathematiques

    2005-09-01

    This paper proves the existence of multiple solutions to the Coulomb friction problem with Signorini contact conditions in continuum linear elasticity. We consider a body lying on a rigid foundation and we propose a method in order to exhibit two solutions to the frictional contact problem when the friction coefficient is large enough: one solution which separates from the foundation and another one which remains stuck on the foundation. We apply the method to the simple class of problems with triangular bodies and linear displacement fields and we describe the cases in which such multiple solutions exist. Denoting by {mu} the friction coefficient, we come to the conclusion that such nonuniqueness cases may appear when {mu}>1. (orig.)

  14. Identification of multiple HPV types on spermatozoa from human sperm donors.

    Science.gov (United States)

    Kaspersen, Maja D; Larsen, Peter B; Ingerslev, Hans Jakob; Fedder, Jens; Petersen, Gert Bruun; Bonde, Jesper; Höllsberg, Per

    2011-03-29

    Human papillomaviruses (HPV) may cause sexually transmitted disease. High-risk types of HPV are involved in the development of cervical cell dysplasia, whereas low-risk types may cause genital condyloma. Despite the association between HPV and cancer, donor sperm need not be tested for HPV according to European regulations. Consequently, the potential health risk of HPV transmission by donor bank sperm has not been elucidated, nor is it known how HPV is associated with sperm. The presence of 35 types of HPV was examined on DNA from semen samples of 188 Danish sperm donors using a sensitive HPV array. To examine whether HPV was associated with the sperm, in situ hybridization were performed with HPV-6, HPV-16 and -18, and HPV-31-specific probes. The prevalence of HPV-positive sperm donors was 16.0% and in 66.7% of these individuals high-risk types of HPV were detected. In 5.3% of sperm donors, two or more HPV types were detected. Among all identified HPV types, 61.9% were high-risk types. In situ hybridization experiments identified HPV genomes particularly protruding from the equatorial segment and the tail of the sperm. Semen samples from more than one in seven healthy Danish donors contain HPV, most of them of high-risk types binding to the equatorial segment of the sperm cell. Most HPV-positive sperm showed decreased staining with DAPI, indicative of reduced content of DNA. Our data demonstrate that oncogenic HPV types are frequent in men.

  15. Acute renal failure as an initial manifestation of Multiple Endocrine Neoplasia (MEN Type 1

    Directory of Open Access Journals (Sweden)

    Reza Afshar

    2012-01-01

    Full Text Available Multiple endocrine neoplasia (MEN is a group of heritable syndromes characterized by aberrant growth of benign or malignant tumors in a subset of endocrine tissues. There are three major syndromes: MEN1, 2A and 2B. We describe a 60-year-old woman who initially manifested acute renal failure due to hypercalcemia and dehydration and, finally, was diagnosed as a sporadic MEN1 case.

  16. A comparison of multiple sclerosis clinical disease activity between patients treated with natalizumab and fingolimod

    DEFF Research Database (Denmark)

    Koch-Henriksen, Nils; Magyari, Melinda; Sellebjerg, Finn;

    2016-01-01

    BACKGROUND: Natalizumab and fingolimod were approved for treatment of active relapsing-remitting multiple sclerosis (RRMS) in Denmark in 2006 and 2011, respectively. There have been no randomized head-to-head studies comparing the two drugs. OBJECTIVE: To compare the clinical efficacy...... of natalizumab and fingolimod. METHODS: Data on all Danish RRMS patients who started their first second-line treatment with natalizumab or fingolimod from July 2011 to March 2015 were prospectively recorded in the Danish Multiple Sclerosis (MS) Treatment Register. The two treatment arms were 1:1 propensity score...

  17. ACTIVE CONTROL OF A FLEXIBLE CANTILEVER PLATE WITH MULTIPLE TIME DELAYS

    Institute of Scientific and Technical Information of China (English)

    Longxiang Chen; Ji Pan; Guoping Cai

    2008-01-01

    Active control of a flexible cantilever plate with multiple time delays is investigated using the discrete optimal control method.A controller with multiple time delays is presented.In this controller,time delay effect is incorporated in the mathematical model of the dynamic system throughout the control design and no approximations and assumptions are made in the controller derivation,so the system stability is easily guaranteed.Furthermore,this controller is available for both small time delays and large time delays.The feasibility and efficiency of the proposed controller are verified through numerical simulations in the end of this paper.

  18. Cellulase occurs in multiple active forms in ripe avocado fruit mesocarp.

    Science.gov (United States)

    Kanellis, A K; Kalaitzis, P

    1992-02-01

    The existence of multiple forms of avocado (Persea americana Mill. cv Hass) cellulase in crude protein extracts of ripe avocado fruit is reported. Cellulase was separated into at least 11 multiple forms by native isoelectric focusing in the pH range between 4 and 7 and visualized by both activity staining using Congo red and immunostaining. The enzyme components were acidic proteins with isoelectric points in the range of pH 5.10 to 6.80, the predominant forms having isoelectric points of 5.60, 5.80, 5.95, and 6.20. All 11 forms were immunologically related with molecular masses of 54 kilodaltons.

  19. Semi-active control of a cable-stayed bridge under multiple-support excitations

    Institute of Scientific and Technical Information of China (English)

    代泽兵; 黄金枝; 王红霞

    2004-01-01

    This paper presents a semi-active strategy for seismic protection of a benchmark cable-stayed bridge with consideration of multiple-support excitations. In this control strategy, Magnetorheological (MR) dampers are proposed as control devices, a LQG-clipped-optimal control algorithm is employed. An active control strategy, shown in previous researches to perform well at controlling the benchmark bridge when uniform earthquake motion was assumed, is also used in this study to control this benchmark bridge with consideration of multiple-support excitations. The performance of active control system is compared to that of the presented semi-active control strategy. Because the MR fluid damper is a controllable energy- dissipation device that cannot add mechanical energy to the structural system, the proposed control strategy is fail-safe in that bounded-input, bounded-output stability of the controlled structure is guaranteed. The numerical results demonstrated that the performance of the presented control design is nearly the same as that of the active control system; and that the MR dampers can effectively be used to control seismically excited cable-stayed bridges with multiple-support excitations.

  20. Epidemiological analysis of demographic characteristics and type of injuries in patients with multiple trauma with respect to conclusive treatment outcome

    Directory of Open Access Journals (Sweden)

    Zagorac Slaviša

    2008-01-01

    Full Text Available Introduction Multiple trauma is one of the leading causes of mortality and morbidity in the population of people under 45 years of age. The consequences of multiple trauma have huge epidemiological, social and economic significance. Objective The aim of the paper was to analyze the conclusive treatment outcome of multiply traumatized patients with respect to their sex, age, injury mechanism and type. METHOD This retrospective study included 100 patients with multiple injuries (ISS>16 treated in the Emergency Room of the Clinical Centre of Serbia in the course of 2004. Clinical, X-ray, laboratory and numerical presentation methods - scores (ISS and GCS were used to show the injury severity. Results Most of the injured were males (80%, and the average age was 40±20 (5-83. Out of the total number of patients who died, 23 (82% were males, and 5 (18% were females. The average age of the patients with fatal outcomes was 48±21 (8-86. Traffic accidents were the leading cause of injury (59%. The median GCS was 10±3 (3-15. The average ISS was 30 (20-66 in the surviving patients, and 53 (27-77 in those who died. Conclusion With respect to sex, in most cases multiple trauma affects males (p<0.01, with the average age of about 40. With respect to injury mechanism, the main cause of the occurrence of multiple trauma is traffic accidents (p<0.01. There is a statistically significant difference in the values of GCS and ISS relative to the definitive outcome (p<0.01. Statistical data processing indicated that there was a statistically significant correlation between mortality and type of injury in a given organic system (p<0.01, but that there was no statistically significant correlation between mortality and age. .

  1. Antiviral activity of four types of bioflavonoid against dengue virus type-2

    Directory of Open Access Journals (Sweden)

    Zandi Keivan

    2011-12-01

    Full Text Available Abstract Background Dengue is a major mosquito-borne disease currently with no effective antiviral or vaccine available. Effort to find antivirals for it has focused on bioflavonoids, a plant-derived polyphenolic compounds with many potential health benefits. In the present study, antiviral activity of four types of bioflavonoid against dengue virus type -2 (DENV-2 in Vero cell was evaluated. Anti-dengue activity of these compounds was determined at different stages of DENV-2 infection and replication cycle. DENV replication was measured by Foci Forming Unit Reduction Assay (FFURA and quantitative RT-PCR. Selectivity Index value (SI was determined as the ratio of cytotoxic concentration 50 (CC50 to inhibitory concentration 50 (IC50 for each compound. Results The half maximal inhibitory concentration (IC50 of quercetin against dengue virus was 35.7 μg mL-1 when it was used after virus adsorption to the cells. The IC50 decreased to 28.9 μg mL-1 when the cells were treated continuously for 5 h before virus infection and up to 4 days post-infection. The SI values for quercetin were 7.07 and 8.74 μg mL-1, respectively, the highest compared to all bioflavonoids studied. Naringin only exhibited anti-adsorption effects against DENV-2 with IC50 = 168.2 μg mL-1 and its related SI was 1.3. Daidzein showed a weak anti-dengue activity with IC50 = 142.6 μg mL-1 when the DENV-2 infected cells were treated after virus adsorption. The SI value for this compound was 1.03. Hesperetin did not exhibit any antiviral activity against DENV-2. The findings obtained from Foci Forming Unit Reduction Assay (FFURA were corroborated by findings of the qRT-PCR assays. Quercetin and daidzein (50 μg mL-1 reduced DENV-2 RNA levels by 67% and 25%, respectively. There was no significant inhibition of DENV-2 RNA levels with naringin and hesperetin. Conclusion Results from the study suggest that only quercetin demonstrated significant anti-DENV-2 inhibitory activities. Other

  2. Glatiramer acetate antibodies, gene expression and disease activity in multiple sclerosis

    DEFF Research Database (Denmark)

    Sellebjerg, Finn Thorup; Hedegaard, Chris Juul; Krakauer, M;

    2011-01-01

    Background: Glatiramer acetate (GA) treatment suppresses disease activity in multiple sclerosis (MS). The immunological response to treatment may differ in patients who are stable on GA therapy and patients with breakthrough disease activity, but the results of previous studies are inconsistent....... Objectives: We studied the immunological response to GA and its relationship with disease activity. Methods: Anti-GA antibodies in plasma and the expression of genes encoding cytokines and T-cell-polarizing transcription factors in blood cells were analysed by flow cytometric bead array and polymerase chain...

  3. In-depth discrimination of aerosol types using multiple clustering techniques over four locations in Indo-Gangetic plains

    Science.gov (United States)

    Bibi, Humera; Alam, Khan; Bibi, Samina

    2016-11-01

    Discrimination of aerosol types is essential over the Indo-Gangetic plain (IGP) because several aerosol types originate from different sources having different atmospheric impacts. In this paper, we analyzed a seasonal discrimination of aerosol types by multiple clustering techniques using AERosol RObotic NETwork (AERONET) datasets for the period 2007-2013 over Karachi, Lahore, Jaipur and Kanpur. We discriminated the aerosols into three major types; dust, biomass burning and urban/industrial. The discrimination was carried out by analyzing different aerosol optical properties such as Aerosol Optical Depth (AOD), Angstrom Exponent (AE), Extinction Angstrom Exponent (EAE), Abortion Angstrom Exponent (AAE), Single Scattering Albedo (SSA) and Real Refractive Index (RRI) and their interrelationship to investigate the dominant aerosol types and to examine the variation in their seasonal distribution. The results revealed that during summer and pre-monsoon, dust aerosols were dominant while during winter and post-monsoon prevailing aerosols were biomass burning and urban industrial, and the mixed type of aerosols were present in all seasons. These types of aerosol discriminated from AERONET were in good agreement with CALIPSO (the Cloud-Aerosol Lidar and Infrared Pathfinder Satellite Observation) measurement.

  4. Mathematical modeling and modification of an activated sludge benchmark process evaluated by multiple performance criteria

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Wenliang; Yao, Chonghua [East China University of Science and Technology, Shanghai (China); Lu, Xiwu [Southeast University, Nanjing (China)

    2014-08-15

    Optimal modification of an activated sludge process (ASP) evaluated by multiple performance criteria was studied. A benchmark process in BSM1 was taken as a target process. Four indexes of percentage of effluent violation (PEV), energy consumption (OCI), total volume of tanks (TV) and total suspended solid in tank5 (TSSa5), were criteria and eleven process parameters were decision variables, making up the multiple criteria optimization model, which was solved by non-dominated sorting genetic algorithm II (NSGA-II) in MATLAB. Pareto solutions were obtained; one solution (opt1) was selected based on the authors' decision for a further analysis. Results show that the process with opt1 strategy exhibits much better performance of PEV and OCI than with the default, being improved by 74.17% and 9.97% specifically under dry influent and without control. These results indicated that the multiple criterion optimization method is very useful for modification of an ASP.

  5. Dynamic activity of NF-κ B in multiple trauma patients and protective effects of ulinastain

    Institute of Scientific and Technical Information of China (English)

    LI Jun; WANG Hu; LI Neng-ping; GU Yong-feng; YANG Xin; LU Xiao-bing; CONG Jian-nong; LING Yun; TANG Jiang-an; YUAN Xiao-yan

    2011-01-01

    Objective:To investigate the dynamic activity of NF-κ B at the early stage of injury in multiple trauma patients and the protective effects of ulinastain.Methods:From January 2008 to May 2010,patients with multiple traumas admitted to our emergency department were enrolled in this study.Their age varied from 20-55 years.All enrolled patients were assigned randomly into control group (26 cases of multiple injury without ulinastain treatment),ulinastain group (25 cases of multiple injury with ulinastain treatment),and mild injury group (20 cases) for basic control.The inclusion criteria for mild injury group were AIS-2005 ≤ 3,single wound,previously healthy inhospital patients without the history of surgical intervention.In addition to routine treatment,patients in ulinastain group were intravenously injected 200 000 IU of ulinastain dissolved in 100 ml of normal saline within 12hours after injury and subsequently injected at the interval of every 8 hours for 7 days.NF- κ B activity in monocytes and the level of TNF- α,IL-1,IL-6 in serum on admission (day 0),day 1,2,3,4,and 7 were measured.Data were compared and analyzed between different groups.Results:NF-κB activity in monocytes and TNF- αIL-1 and IL-6 of these patients reached peak levels at 24hour after trauma,with gradual decrease to normal at 72hour after trauma.NF-κ B activity and levels of TNF- a,IL-l and IL-6 were lower in ulinastain group than control one,without any significant difference between the two groups.The mean duration for systemic inflammatory response syndrome and multiple organ dysfunction syndrome was 7 d±3.1 d and 10 d±3.5 d in ulinastain group and control group respectively,and showed a significant difference.Conclusions:NF-κB activity in monocytes and the levels of inflammatory cytokines in multiply injured patients increased transiently at the early stage of trauma.Ulinastain may shorten the duration of systemic inflammatory response syndrome and multiple organ dysfunction

  6. Unexpected Activity of a Novel Kunitz-type Inhibitor

    Science.gov (United States)

    Smith, David; Tikhonova, Irina G.; Jewhurst, Heather L.; Drysdale, Orla C.; Dvořák, Jan; Robinson, Mark W.; Cwiklinski, Krystyna; Dalton, John P.

    2016-01-01

    Kunitz-type (KT) protease inhibitors are low molecular weight proteins classically defined as serine protease inhibitors. We identified a novel secreted KT inhibitor associated with the gut and parenchymal tissues of the infective juvenile stage of Fasciola hepatica, a helminth parasite of medical and veterinary importance. Unexpectedly, recombinant KT inhibitor (rFhKT1) exhibited no inhibitory activity toward serine proteases but was a potent inhibitor of the major secreted cathepsin L cysteine proteases of F. hepatica, FhCL1 and FhCL2, and of human cathepsins L and K (Ki = 0.4-27 nm). FhKT1 prevented the auto-catalytic activation of FhCL1 and FhCL2 and formed stable complexes with the mature enzymes. Pulldown experiments from adult parasite culture medium showed that rFhKT1 interacts specifically with native secreted FhCL1, FhCL2, and FhCL5. Substitution of the unusual P1 Leu15 within the exposed reactive loop of FhKT1 for the more commonly found Arg (FhKT1Leu15/Arg15) had modest adverse effects on the cysteine protease inhibition but conferred potent activity against the serine protease trypsin (Ki = 1.5 nm). Computational docking and sequence analysis provided hypotheses for the exclusive binding of FhKT1 to cysteine proteases, the importance of the Leu15 in anchoring the inhibitor into the S2 active site pocket, and the inhibitor's selectivity toward FhCL1, FhCL2, and human cathepsins L and K. FhKT1 represents a novel evolutionary adaptation of KT protease inhibitors by F. hepatica, with its prime purpose likely in the regulation of the major parasite-secreted proteases and/or cathepsin L-like proteases of its host. PMID:27422822

  7. Diagnosis of Single- or Multiple-Canal Benign Paroxysmal Positional Vertigo according to the Type of Nystagmus

    Directory of Open Access Journals (Sweden)

    Dimitris G. Balatsouras

    2011-01-01

    Full Text Available Benign paroxysmal positional vertigo (BPPV is a common peripheral vestibular disorder encountered in primary care and specialist otolaryngology and neurology clinics. It is associated with a characteristic paroxysmal positional nystagmus, which can be elicited with specific diagnostic positional maneuvers, such as the Dix-Hallpike test and the supine roll test. Current clinical research focused on diagnosing and treating various types of BPPV, according to the semicircular canal involved and according to the implicated pathogenetic mechanism. Cases of multiple-canal BPPV have been specifically investigated because until recently these were resistant to treatment with standard canalith repositioning procedures. Probably, the most significant factor in diagnosis of the type of BPPV is observation of the provoked nystagmus, during the diagnostic positional maneuvers. We describe in detail the various types of nystagmus, according to the canals involved, which are the keypoint to accurate diagnosis.

  8. Bicyclic Peptide Inhibitor of Urokinase-Type Plasminogen Activator

    DEFF Research Database (Denmark)

    Roodbeen, Renée; Paaske, Berit; Jiang, Longguang;

    2013-01-01

    The development of protease inhibitors for pharmacological intervention has taken a new turn with the use of peptidebased inhibitors. Here, we report the rational design of bicyclic peptide inhibitors of the serine protease urokinase-type plasminogen activator (uPA), based on the established...... monocyclic peptide, upain-2. It was successfully converted to a bicyclic peptide, without loss of inhibitory properties. The aim was to produce a peptide cyclised by an amide bond with an additional stabilising across-the-ring covalent bond. We expected this bicyclic peptide to exhibit a lower entropic...... burden upon binding. Two bicyclic peptides were synthesised with affinities similar to that of upain-2, and their binding energetics were evaluated by isothermal titration calorimetry. Indeed, compared to upain-2, the bicyclic peptides showed reduced loss of entropy upon binding to uPA. We also...

  9. Zeeman-Doppler imaging of active young solar type stars

    CERN Document Server

    Hackman, Thomas; Rosén, Lisa; Kochukhov, Oleg; Käpylä, Maarit J

    2015-01-01

    By studying young magnetically active late-type stars, i.e. analogues to the young Sun, one can draw conclusions on the evolution of the solar dynamo. We determine the topology of the surface magnetic field and study the relation between the magnetic field and cool photospheric spots in three young late-type stars. High-resolution spectropolarimetry of the targets were obtained with the HARPSpol instrument mounted at the ESO 3.6 m telescope. The signal-to-noise ratio of the Stokes IV measurements were boosted by combining the signal from a large number of spectroscopic absorption lines through the least squares deconvolution technique. Surface brightness and magnetic field maps were calculated using the Zeeman-Doppler imaging technique. All the three targets show clear signs of both magnetic fields and cool spots. Only one of the targets, namely V1358 Ori, shows evidence of the dominance of non-axisymmetric modes. In two of the targets, the poloidal field is significantly stronger than the toroidal one, indic...

  10. Polyvalent type IV sensitizations to multiple fragrances and a skin protection cream in a metal worker.

    Science.gov (United States)

    Tanko, Zita; Shab, Arna; Diepgen, Thomas Ludwig; Weisshaar, Elke

    2009-06-01

    Fragrances are very common in everyday products. A metalworker with chronic hand eczema and previously diagnosed type IV sensitizations to epoxy resin, balsam of Peru, fragrance mix and fragrance mix II was diagnosed with additional type IV sensitizations to geraniol, hydroxycitronellal, lilial, tree moss, oak moss absolute, citral, citronellol, farnesol, Lyral, fragrance mix II and fragrance mix (with sorbitan sesquioleate). In addition, a type IV sensitization to the skin protection cream containing geraniol and citronellol used at the workplace was detected, and deemed occupationally relevant in this case. The patient could have had contact to fragrances through private use of cosmetics and detergents. On the other hand, the fragrance-containing skin protection cream supports occupational exposure. This case report demonstrates that fragrance contact allergy has to be searched for and clarified individually, which requires a thorough history and a detailed analysis of the work place.

  11. Regulation of muscle growth by multiple ligands signaling through activin type II receptors

    Science.gov (United States)

    Lee, Se-Jin; Reed, Lori A.; Davies, Monique V.; Girgenrath, Stefan; Goad, Mary E. P.; Tomkinson, Kathy N.; Wright, Jill F.; Barker, Christopher; Ehrmantraut, Gregory; Holmstrom, James; Trowell, Betty; Gertz, Barry; Jiang, Man-Shiow; Sebald, Suzanne M.; Matzuk, Martin; Li, En; Liang, Li-fang; Quattlebaum, Edwin; Stotish, Ronald L.; Wolfman, Neil M.

    2005-01-01

    Myostatin is a secreted protein that normally functions as a negative regulator of muscle growth. Agents capable of blocking the myostatin signaling pathway could have important applications for treating human muscle degenerative diseases as well as for enhancing livestock production. Here we describe a potent myostatin inhibitor, a soluble form of the activin type IIB receptor (ACVR2B), which can cause dramatic increases in muscle mass (up to 60% in 2 weeks) when injected into wild-type mice. Furthermore, we show that the effect of the soluble receptor is attenuated but not eliminated in Mstn-/- mice, suggesting that at least one other ligand in addition to myostatin normally functions to limit muscle growth. Finally, we provide genetic evidence that these ligands signal through both activin type II receptors, ACVR2 and ACVR2B, to regulate muscle growth in vivo. PMID:16330774

  12. Learning styles and types of multiple intelligences in dental students in their first and tenth semester. Monterrey, Mexico, 2015.

    Directory of Open Access Journals (Sweden)

    Juan Solís-Soto

    2016-04-01

    Full Text Available Introduction: Nowadays the incorporation and validation of learning styles and multiple intelligences enable teachers to obtain positive results in academic performance. This new approach has allowed to appreciate personal differences in dental students and strengthen their underdeveloped aspects, improving teaching and learning skills. Objective: To compare learning styles and multiple intelligences in a sample of Mexican dental students in their first and tenth semester. Materials and Methods: A cross-sectional study using questionnaires on learning styles (Honey-Alonso and Gardner’s multiple intelligences was performed. The study was applied to 123 students in their first semester and 157 in their tenth semester at the School of Dentistry at Universidad Autónoma de Nuevo León, evaluating differences between age and sex. Results: Logical-Mathematical intelligence (p=0.044 and Kinesthetic-Corporal intelligence (p=0.042 showed significant differences between students of both semesters, with intrapersonal and interpersonal intelligences being more prevalent. Within learning styles, the prevalent were Reflexive and Theoretical, showing a significant difference between semesters (p=0.005. Conclusion: The most prevalent learning styles in both groups were Reflexive and Theoretical, with no difference between both sexes. The most prevalent types of multiple intelligences in both sexes and groups were interpersonal and intrapersonal.

  13. Mating Type Loci of Sporisorium reilianum: Novel Pattern with Three a and Multiple b Specificities

    OpenAIRE

    Schirawski, Jan; Heinze, Bernadette; Wagenknecht, Martin; Kahmann, Regine

    2005-01-01

    Sporisorium reilianum and Ustilago maydis are two closely related smut fungi, which both infect maize but differ fundamentally in their mode of plant invasion and site of symptom development. As a prelude to studying the molecular basis of these differences, we have characterized the mating type loci of S. reilianum. S. reilianum has two unlinked mating type loci, a and b. Genes in both loci and adjacent regions show a high degree of synteny to the corresponding genes of U. maydis. The b locu...

  14. Patterns of cervical coinfection with multiple human papilloma virus types in a screening population in Denmark

    DEFF Research Database (Denmark)

    Goldman, Bryan; Rebolj, Matejka; Rygaard, Carsten

    2013-01-01

    Patterns of cervical human papillomavirus (HPV) infection suggest that HPV genotypes are not independent of each other. This may be explained by risk factors common to all HPV infections, but type-specific biological factors may also play a role. This raises the question of whether widespread use...

  15. Pathways Targeted by Antidiabetes Drugs Are Enriched for Multiple Genes Associated With Type 2 Diabetes Risk

    NARCIS (Netherlands)

    Segre, Ayellet V.; Wei, Nancy; Altshuler, David; Florez, Jose C.; Wijmenga, T. N.; Ostaptchouk, J. V.

    2015-01-01

    Genome-wide association studies (GWAS) have uncovered >65 common variants associated with type 2 diabetes (T2D); however, their relevance for drug development is not yet clear. Of note, the first two T2D-associated loci (PPARG and KCNJ11/ABCC8) encode known targets of antidiabetes medications. We th

  16. Campylobacter fetus subspecies contain conserved type IV secretion systems on multiple genomic islands and plasmids

    NARCIS (Netherlands)

    Graaf-Van Bloois, Van Der Linda; Miller, William G.; Yee, Emma; Wagenaar, Jaap A.

    2016-01-01

    The features contributing to differences in pathogenicity of the Campylobacter fetus subspecies are unknown. Putative factors involved in pathogenesis are located in genomic islands that encode a type IV secretion system (T4SS) and fic domain (filamentation induced by cyclic AMP) proteins, which

  17. U12 type introns were lost at multiple occasions during evolution

    Directory of Open Access Journals (Sweden)

    Bartschat Sebastian

    2010-02-01

    Full Text Available Abstract Background Two categories of introns are known, a common U2 type and a rare U12 type. These two types of introns are removed by distinct spliceosomes. The phylogenetic distribution of spliceosomal RNAs that are characteristic of the U12 spliceosome, i.e. the U11, U12, U4atac and U6atac RNAs, suggest that U12 spliceosomes were lost in many phylogenetic groups. We have now examined the distribution of U2 and U12 introns in many of these groups. Results U2 and U12 introns were predicted by making use of available EST and genomic sequences. The results show that in species or branches where U12 spliceosomal components are missing, also U12 type of introns are lacking. Examples are the choanoflagellate Monosiga brevicollis, Entamoeba histolytica, green algae, diatoms, and the fungal lineage Basidiomycota. Furthermore, whereas U12 splicing does not occur in Caenorhabditis elegans, U12 introns as well as U12 snRNAs are present in Trichinella spiralis, which is deeply branching in the nematode tree. A comparison of homologous genes in T. spiralis and C. elegans revealed different mechanisms whereby U12 introns were lost. Conclusions The phylogenetic distribution of U12 introns and spliceosomal RNAs give further support to an early origin of U12 dependent splicing. In addition, this distribution identifies a large number of instances during eukaryotic evolution where such splicing was lost.

  18. IgGs containing light chains of the lambda and kappa type and of all subclasses (IgG1-IgG4) from sera of patients with multiple sclerosis hydrolyze DNA.

    Science.gov (United States)

    Parkhomenko, Taisiya A; Legostaeva, Galina A; Doronin, Boris M; Buneva, Valentina N; Nevinsky, Georgy A

    2010-01-01

    We present the first evidence demonstrating that small fractions of IgGs of all four subclasses (IgG1-IgG4) are catalytically active in the hydrolysis of DNA and on average their relative activity (nM supercoiled DNA/1mg IgG/1 h) increases in the order: IgG1 (0.58) light chains of the lambda-type are severalfold more active in the hydrolysis of DNA than IgGs with light chains of the kappa-type. Using different physicochemical methods of antibody analysis we have shown that the immune system of multiple sclerosis patients generates a variety of anti-DNA abzymes of different type and with different catalytic properties, which can play an important role in multiple sclerosis pathogenesis.

  19. Attributions and self-efficacy for physical activity in multiple sclerosis.

    Science.gov (United States)

    Nickel, D; Spink, K; Andersen, M; Knox, K

    2014-01-01

    Self-efficacy is an important predictor of health-related physical activity in multiple sclerosis (MS). While past experiences are believed to influence efficacy beliefs, the explanations individuals provide for these experiences also may be critical. Our objective was to test the hypothesis that perceived success or failure to accumulate 150 min of physical activity in the previous week would moderate the relationship between the attributional dimension of stability and self-efficacy to exercise in the future. Forty-two adults with MS participated in this cross-sectional descriptive study. Participants completed questions assessing physical activity, perceived outcome for meeting the recommended level of endurance activity, attributions for the outcome, and exercise self-efficacy. Results from hierarchical multiple regression revealed a significant main effect for perceived outcome predicting self-efficacy that was qualified by a significant interaction. The final model, which included perceived outcome, stability, and the interaction term, predicted 37% of the variance in exercise self-efficacy, F (3, 38) = 7.27, p = .001. Our findings suggest that the best prediction of self-efficacy in the MS population may include the interaction of specific attributional dimensions with success/failure at meeting the recommended physical activity dose. Attributions may be another target for interventions aimed at increasing the physical activity in MS.

  20. Evidence from intrinsic activity that asymmetry of the human brain is controlled by multiple factors.

    Science.gov (United States)

    Liu, Hesheng; Stufflebeam, Steven M; Sepulcre, Jorge; Hedden, Trey; Buckner, Randy L

    2009-12-01

    Cerebral lateralization is a fundamental property of the human brain and a marker of successful development. Here we provide evidence that multiple mechanisms control asymmetry for distinct brain systems. Using intrinsic activity to measure asymmetry in 300 adults, we mapped the most strongly lateralized brain regions. Both men and women showed strong asymmetries with a significant, but small, group difference. Factor analysis on the asymmetric regions revealed 4 separate factors that each accounted for significant variation across subjects. The factors were associated with brain systems involved in vision, internal thought (the default network), attention, and language. An independent sample of right- and left-handed individuals showed that hand dominance affects brain asymmetry but differentially across the 4 factors supporting their independence. These findings show the feasibility of measuring brain asymmetry using intrinsic activity fluctuations and suggest that multiple genetic or environmental mechanisms control cerebral lateralization.

  1. Reinforcement of a plate weakened by multiple holes with several patches for different types of plate-patch attachment

    KAUST Repository

    Zemlyanova, A.

    2014-01-24

    The most general situation of the reinforcement of a plate with multiple holes by several patches is considered. There is no restriction on the number and the location of the patches. Two types of patch attachment are considered: only along the boundary of the patch or both along the boundary of the patch and the boundaries of the holes which this patch covers. The unattached boundaries of the holes may be loaded with given in-plane stresses. The mechanical problem is reduced to a system of singular integral equations which can be further reduced to a system of Fredholm equations. A new numerical procedure for the solution of the system of singular integral equations is proposed in this paper. It is demonstrated on numerical examples that this procedure has advantages in the case of multiple patches and holes and allows achievement of better numerical convergence with less computational effort.

  2. Generalization of an Active Electronic Notebook for Teaching Multiple Programming Languages

    OpenAIRE

    Torabzadeh-Tari, Mohsen; Fritzson, Peter; Pop, Adrian; Sjölund, Martin

    2010-01-01

    In this paper we present a generalization of the active electronic notebook, OMNotebook, for handling multiple programming languages for educational purposes. OMNotebook can be an alternative or complementary tool to the traditional teaching method with lecturing and reading textbooks. Experience shows that using such an electronic book will lead to more engagement from the students. OMNotebook can contain technical computations and text, as well as graphics. Hence it is a suitable tool for t...

  3. Plasminogen activator inhibitor type 1 regulates microglial motility and phagocytic activity

    Directory of Open Access Journals (Sweden)

    Jeon Hyejin

    2012-06-01

    Full Text Available Abstract Background Plasminogen activator inhibitor type 1 (PAI-1 is the primary inhibitor of urokinase type plasminogen activators (uPA and tissue type plasminogen activators (tPA, which mediate fibrinolysis. PAI-1 is also involved in the innate immunity by regulating cell migration and phagocytosis. However, little is known about the role of PAI-1 in the central nervous system. Methods In this study, we identified PAI-1 in the culture medium of mouse mixed glial cells by liquid chromatography and tandem mass spectrometry. Secretion of PAI-1 from glial cultures was detected by ELISA and western blotting analysis. Cell migration was evaluated by in vitro scratch-wound healing assay or Boyden chamber assay and an in vivo stab wound injury model. Phagocytic activity was measured by uptake of zymosan particles. Results The levels of PAI-1 mRNA and protein expression were increased by lipopolysaccharide and interferon-γ stimulation in both microglia and astrocytes. PAI-1 promoted the migration of microglial cells in culture via the low-density lipoprotein receptor-related protein (LRP 1/Janus kinase (JAK/signal transducer and activator of transcription (STAT1 axis. PAI-1 also increased microglial migration in vivo when injected into mouse brain. PAI-1-mediated microglial migration was independent of protease inhibition, because an R346A mutant of PAI-1 with impaired PA inhibitory activity also promoted microglial migration. Moreover, PAI-1 was able to modulate microglial phagocytic activity. PAI-1 inhibited microglial engulfment of zymosan particles in a vitronectin- and Toll-like receptor 2/6-dependent manner. Conclusion Our results indicate that glia-derived PAI-1 may regulate microglial migration and phagocytosis in an autocrine or paracrine manner. This may have important implications in the regulation of brain microglial activities in health and disease.

  4. Preliminary Study Results Of Multiple Drug Resistance In Patients With Advanced Types Of Colorectal Cancer

    Directory of Open Access Journals (Sweden)

    S Navruzov

    2010-04-01

    Full Text Available In the department of coloproctology of NORC MH RUz 17 patients with disseminated forms of colorectal cancer was made the study of oncogenes and complex treatment by 2 protocols using FOLFOX-4 regime and FOLFIRI regime. In second protocol there used 2 sessions of endolymphatical polychemotherapy FOLFOX-4 regime against EHF-hyperthermia. All patients were performed additional investigations directed to study the presence of multiple drug resistance in them where definition of р53, bcl-2 oncogene expression. In our observations we followed resistance to FOLFOX-4 scheme in 4 patients, and to FOLFIRI scheme in 2 cases. In our studies hyperexpression of oncoproteine  р53 was correlated with the effect of conducted therapy whereas hyperexpression of oncoproteine bcl-2 showed therapy resistance. 

  5. Multiple Images of a Highly Magnified Supernova Formed by an Early-Type Cluster Galaxy Lens

    CERN Document Server

    Kelly, Patrick L; Treu, Tommaso; Foley, Ryan J; Brammer, Gabriel; Schmidt, Kasper B; Zitrin, Adi; Sonnenfeld, Alessandro; Strolger, Louis-Gregory; Graur, Or; Filippenko, Alexei V; Jha, Saurabh W; Riess, Adam G; Bradac, Marusa; Weiner, Benjamin J; Scolnic, Daniel; Malkan, Matthew A; von der Linden, Anja; Trenti, Michele; Hjorth, Jens; Gavazzi, Raphael; Fontana, Adriano; Merten, Julian; McCully, Curtis; Jones, Tucker; Postman, Marc; Dressler, Alan; Patel, Brandon; Cenko, S Bradley; Graham, Melissa L; Tucker, Bradley E

    2014-01-01

    We report the discovery of the first multiply-imaged gravitationally-lensed supernova. The four images form an Einstein cross with over 2" diameter around a z=0.544 elliptical galaxy that is a member of the cluster MACSJ1149.6+2223. The supernova appeared in Hubble Space Telescope exposures taken on 3-20 November 2014 UT, as part of the Grism Lens-Amplified Survey from Space. The images of the supernova coincide with the strongly lensed arm of a spiral galaxy at z=1.491, which is itself multiply imaged by the cluster potential. A measurement of the time delays between the multiple images and their magnification will provide new unprecedented constraints on the distribution of luminous and dark matter in the lensing galaxy and in the cluster, as well as on the cosmic expansion rate.

  6. Development of autoimmune hepatitis type I after pulsed methylprednisolone therapy for multiple sclerosis: A case report

    Institute of Scientific and Technical Information of China (English)

    Atsushi Takahashi; Hirornasa Ohira; Yukiko Kanno; Yuta Takahashi; Natsumi Sakamoto; Kyoko Monoe; Hironobu Saito; Kazumichi Abe; Junko Yokokawa; Atsushi Irisawa

    2008-01-01

    A 43-year-old woman with multiple sclerosis (MS) was treated with pulsed methylprednisolone and interferon β at a hospital.Four weeks after initiating treatment,liver dysfunction occurred and she was referred and admitted to our hospital.Clinical and laboratory findings were consistent with and fulfilled the criteria for drug-induced hepatitis,but not for autoimmune hepatitis (AIH).She was successfully treated with corticosteroids.As ataxia developed after 1 year,she was treated with pulsed methylprednisolone for 3 days,then readmitted to our hospital when liver dysfunction occurred.Clinical and laboratory findings led to the diagnosis of A[H.To the best of our knowledge,this is the second case of AIH developed after pulsed methylprednisolone for MS.

  7. Outcome expectations and physical activity in persons with longstanding multiple sclerosis.

    Science.gov (United States)

    Morrison, Janet D; Stuifbergen, Alexa K

    2014-06-01

    Research suggests that persons with multiple sclerosis (MS) are much less physically active than the general population and that increased physical activity in persons with MS is associated with numerous benefits such as improvements in fatigue, mobility, and quality of life (). Potentially modifiable theory-based determinants of physical activity behavior need to be identified so that researchers may study their effectiveness in randomized clinical trials and clinicians may integrate them into practice to promote physical activity in this population. The purpose of this study was to explore the multidimensional (physical, social, and self-evaluative) outcome expectations for physical activity among persons with longstanding MS. A sample of 369 participants diagnosed with MS for more than 15 years completed surveys to measure multidimensional outcome expectations for exercise, MS functional limitations, and physical activity using two different instruments: one measuring physical activity engagement and the other measuring physical activity capability. Results indicated that MS functional limitation was the strongest predictor of both physical activity engagement and physical activity capability. Physical and social outcome expectations contributed to the model explaining 12% of the variation in physical activity engagement, whereas none of the outcome expectancy dimensions (physical, social, or self-evaluative) contributed to the model explaining variation in physical activity capability. Although analyses of cross-sectional data do not infer causation, these findings suggest that positive physical and social outcome expectations for physical activity are associated with engagement in physical activity as well as being potential sources of motivation for increasing physical activity behavior in individuals living with longstanding MS.

  8. The Herpes Simplex Virus Type 1 Multiple Function Protein ICP27

    Institute of Scientific and Technical Information of China (English)

    Lei ZHAO; Wen-bo ZHU; Qiong DING; Gui-qiang PENG; Chun-fu ZHENG

    2008-01-01

    The herpes simplex virus type 1 (HSV-1) infected-cell protein 27 (ICP27) is an essential,highly conserved protein involved in various steps of HSV-1 gene regulation as well as in the shut-off of host gene expression during infection.It functions primarily at the post-transcriptional level in inhibiting precursor mRNA splicing and in promoting nuclear export of viral transcripts.Recently,many novel functions performed by the HSV-1 ICP27 protein were shown,including leptomycin B resistance,inhibition of the type I interferon signaling,regulation of the viral mRNA translation and determining the composition of HSV-1 virions.

  9. Multiple type 2 diabetes susceptibility genes following genome-wide association scan in UK samples

    OpenAIRE

    Zeggini, Eleftheria; Michael N. Weedon; Lindgren, Cecilia M.; Frayling, Timothy M; Elliott, Katherine S.; Lango, Hana; Nicholas J Timpson; Perry, John R B; Nigel W Rayner; Freathy, Rachel M; Barrett, Jeffrey C.; Shields, Beverley; Andrew P Morris; Ellard, Sian; Groves, Christopher J

    2007-01-01

    The molecular mechanisms involved in the development of type 2 diabetes are poorly understood. Starting from genome-wide genotype data for 1,924 diabetic cases and 2,938 population controls generated by the Wellcome Trust Case Control Consortium, we set out to detect replicated diabetes association signals through analysis of 3,757 additional cases and 5,346 controls, and by integration of our findings with equivalent data from other international consortia. We detected diabetes susceptibilit...

  10. Multiple Tumor Types May Originate from Bone Marrow-Derived Cells

    Directory of Open Access Journals (Sweden)

    Chunfang Liu

    2006-09-01

    Full Text Available It was believed that tumors originated from the transformation of their tissue-specific stem cells. However, bone marrow-derived cells (BMDCs, which possess an unexpected degree of plasticity and often reside in other tissues, might also represent a potential source of malignancy. To study whether BMDCs play a role in the source of other tumors, BMDCs from mice were treated with 3-methycholanthrene until malignant transformation was achieved. Here we show that transformed BMDCs could form many tumor types, including epithelial tumors, neural tumors, muscular tumors, tumors of fibroblasts, blood vessel endothelial tumors, and tumors of poor differentiation in vivo. Moreover, a single transformed BMDC has the ability to self-renew, differentiate spontaneously into various types of tumor cells in vitro, express markers associated with multipotency, and form teratoma in vivo. These data suggest that multipotent cancer stem cells seemed to originate from transformed BMDCs. Conclusively, these findings reveal that BMDCs might be a source of many tumor types, even teratoma. In addition, multipotent cancer stem cells might originate from malignant transformed BMDCs.

  11. Diabetes Attitude Scale: validation in type-2 diabetes patients in multiple centers in China.

    Directory of Open Access Journals (Sweden)

    Qingqing Lou

    Full Text Available OBJECTIVE: The aim of the paper is to report the development and psychometric testing of Diabetes Attitude Scale. METHOD: A prospective study was performed. The cultural equivalency and content validity of the Diabetes Attitude Scale were determined by panels of endocrinologists, physiologists, nurses and dieticians. An accurate and usable translation was obtained for each of five subscales examining attitudes on need for special training, the seriousness of type-2 diabetes, the need for controlling the condition, its psychosocial impact and the degree of autonomy given to patients in decision making. The validation was derived from 5961 patients with type-2 diabetes, recruited from 50 centers in 29 provinces throughout China between March 1st and September 30th, 2010. RESULTS: The modified Diabetes Attitude Scale showed an acceptable level of internal consistency. The strength of the inter-correlations among the domains of five subscales suggests that the instrument measures related but separate domains of patients' attitudes toward diabetes. Moreover, the test-retest intraclass correlation coefficients were high enough to support the stability of the Chinese version of the third version of the scale. CONCLUSIONS: The psychometric properties of the Chinese version of Diabetes Attitude Scale demonstrated satisfactory validity and reliability and appeared to effectively evaluate attitudes toward diabetes in patients with type-2 diabetes.

  12. Pituitary Prolactinoma Imaged by 99mTc-Sestamibi SPECT/CT in a Multiple Endocrine Neoplasia Type 1 Patient.

    Science.gov (United States)

    Pan, Yu; Lv, Jing; Guo, Rui; Pan, Mengyi; Zhang, Yifan

    2016-06-01

    A 35-year-old woman who had undergone bilateral inferior parathyroidectomy for primary hyperparathyroidism was referred to our hospital to evaluate the cause of irregular menses, galactorrhea, and paroxysmal headache. Multiple endocrine neoplasia type 1 was then suspected for the high levels of plasma prolactin, parathyroid hormone, serum calcium, insulin, and related symptoms. A Tc-sestamibi SPECT/CT acquired to evaluate parathyroid glands unexpectedly revealed an increased accumulation in the pituitary gland, which was further confirmed by enhanced magnetic resonance imaging as a pituitary microadenoma. Bromocriptine treatment gradually reduced the prolactin level.

  13. On Identifiability of Bias-Type Actuator-Sensor Faults in Multiple-Model-Based Fault Detection and Identification

    Science.gov (United States)

    Joshi, Suresh M.

    2012-01-01

    This paper explores a class of multiple-model-based fault detection and identification (FDI) methods for bias-type faults in actuators and sensors. These methods employ banks of Kalman-Bucy filters to detect the faults, determine the fault pattern, and estimate the fault values, wherein each Kalman-Bucy filter is tuned to a different failure pattern. Necessary and sufficient conditions are presented for identifiability of actuator faults, sensor faults, and simultaneous actuator and sensor faults. It is shown that FDI of simultaneous actuator and sensor faults is not possible using these methods when all sensors have biases.

  14. Optimization and immune recognition of multiple novel conserved HLA-A2, human immunodeficiency virus type 1-specific CTL epitopes

    DEFF Research Database (Denmark)

    Corbet, S; Nielsen, HV; Vinner, L;

    2003-01-01

    MHC-I-restricted cytotoxic responses are considered a critical component of protective immunity against viruses, including human immunodeficiency virus type 1 (HIV-1). CTLs directed against accessory and early regulatory HIV-1 proteins might be particularly effective; however, CTL epitopes....... This study demonstrates the potency of ANNs for identifying putative virus CTL epitopes, and the new HIV-1 CTL epitopes identified should have significant implications for HIV-1 vaccine development. As a novel vaccine approach, it is proposed to increase the coverage of HIV variants by including multiple...

  15. Optimization and immune recognition of multiple novel conserved HLA-A2, human immunodeficiency virus type 1-specific CTL epitopes

    DEFF Research Database (Denmark)

    Corbet, S.; Nielsen, H.V.; Vinner, L.;

    2003-01-01

    MHC-I-restricted cytotoxic responses are considered a critical component of protective immunity against viruses, including human immunodeficiency virus type 1 (HIV-1). CTLs directed against accessory and early regulatory HIV-1 proteins might be particularly effective; however, CTL epitopes...... demonstrates the potency of ANNs for identifying putative virus CTL epitopes, and the new HIV-1 CTL epitopes identified should have significant implications for HIV-1 vaccine development. As a novel vaccine approach, it is proposed to increase the coverage of HIV variants by including multiple anchor...

  16. CD4 T cell activation and disease activity at onset of multiple sclerosis

    DEFF Research Database (Denmark)

    Jensen, J; Langkilde, Annika Reynberg; Fenst, C;

    2004-01-01

    severity. In contrast, the percentage of CD25+ CD4 T cells in cerebrospinal fluid correlated negatively with the cerebrospinal fluid concentration of myelin basic protein and the presence of IgG oligoclonal bands. These results suggest that distinct systemic and intrathecal T cell activation states...

  17. Specific associations between types of physical activity and components of mental health.

    Science.gov (United States)

    Asztalos, Melinda; Wijndaele, Katrien; De Bourdeaudhuij, Ilse; Philippaerts, Renaat; Matton, Lynn; Duvigneaud, Nathalie; Thomis, Martine; Duquet, William; Lefevre, Johan; Cardon, Greet

    2009-07-01

    Findings of previous studies suggest that the relationship between physical activity and mental health may change across different domains of physical activity, different dimensions of mental health, and different population subgroups. The present study examined associations between five types of physical activity with different contents: housework, leisure active transportation, biking to/from work, walking to/from work, and sports participation, and two dimensions of mental health: perceived stress and psychological distress, in 1919 participants aged 20-65 years, using the data from the Flemish Policy Research Centre Sport, Physical Activity and Health. Multiple logistic regression analyses were performed with the total sample, and with the sample stratified by gender, age, and occupational category. Further, separate models were used in the gender and age subgroups of each occupational category. Sports participation was the only type of physical activity inversely associated with both stress (OR=0.375; CI: 0.200-0.704) and distress (OR=0.480; CI: 0.253-0.910). Sports participation related to less distress in unemployed mid-aged adults, and to less stress in unemployed women, unemployed young adults, and young adults with blue-collar jobs. Housework was associated with more stress and more distress in women with blue-collar jobs. In young adults with white-collar jobs, however, an inverse association between housework and distress was found. Biking to and from work was associated with more stress in men with blue-collar jobs. Results invite consideration for the utility, and perhaps the necessity, of differentiated health recommendations for physical health and for mental health in different population subgroups.

  18. Solar Distillation System Based on Multiple-Effect Diffusion Type Still

    KAUST Repository

    Huang, Bin-Juine

    2014-03-01

    The present study intends to develop a high-performance solar-assisted desalination system (SADS) using multi-effect diffusion type still (MEDS) and the vacuum tube solar collector (VTSC). A MEDS prototype was designed and built. The measured result is very close to the estimation. The 10-effect MEDS will produce pure water at about 13.7 L/day/m2 collector area at a solar irradiation of 600 W/m2 and 19.7 L/day/m2 collector area at solar irradiation 800 W/m2. For 20-effect still, the yield rate increase is 32% compared to 10-effect still.

  19. Multiple reflection-asymmetric type band structures in $^{220}Th$ and dinuclear model

    CERN Document Server

    Shneidman, T M; Antonenko, N V; Jolos, R V; Scheid, W

    2010-01-01

    The negative parity bands in $^{220}$Th are analyzed within the dinuclear system model which was previously used for describing the alternating-parity bands in deformed actinides. The model is based on the assumption that cluster type shapes are produced by the motion of nuclear system in the mass-asymmetry coordinate. To describe the reflection-asymmetric collective modes characterized by nonzero values of $K$, the intrinsic excitations of clusters are taken into account. The angular momentum dependence of the parity splitting and the staggering behavior of the $B(E1)/B(E2)$ ratios as functions of angular momentum are explained.

  20. Multiple origins of kdr-type resistance in the house fly, Musca domestica.

    Science.gov (United States)

    Rinkevich, Frank D; Hedtke, Shannon M; Leichter, Cheryl A; Harris, Sarah A; Su, Cathy; Brady, Seán G; Taskin, Vatan; Qiu, Xinghui; Scott, Jeffrey G

    2012-01-01

    Insecticide resistance is a model phenotype that can be used to investigate evolutionary processes underlying the spread of alleles across a global landscape, while offering valuable insights into solving the problems that resistant pests present to human health and agriculture. Pyrethroids are one of the most widely used classes of insecticides world-wide and they exert their toxic effects through interactions with the voltage-sensitive sodium channel (Vssc). Specific mutations in Vssc (kdr, kdr-his and super-kdr) are known to cause resistance to pyrethroid insecticides in house flies. In order to determine the number of evolutionary origins of kdr, kdr-his and super-kdr, we sequenced a region of Vssc from house flies collected in the USA, Turkey and China. Our phylogenetic analysis of Vssc unequivocally supports the hypothesis of multiple independent origins of kdr, super-kdr and kdr-his on an unprecedented geographic scale. The implications of these evolutionary processes on pest management are discussed.

  1. Multiple origins of kdr-type resistance in the house fly, Musca domestica.

    Directory of Open Access Journals (Sweden)

    Frank D Rinkevich

    Full Text Available Insecticide resistance is a model phenotype that can be used to investigate evolutionary processes underlying the spread of alleles across a global landscape, while offering valuable insights into solving the problems that resistant pests present to human health and agriculture. Pyrethroids are one of the most widely used classes of insecticides world-wide and they exert their toxic effects through interactions with the voltage-sensitive sodium channel (Vssc. Specific mutations in Vssc (kdr, kdr-his and super-kdr are known to cause resistance to pyrethroid insecticides in house flies. In order to determine the number of evolutionary origins of kdr, kdr-his and super-kdr, we sequenced a region of Vssc from house flies collected in the USA, Turkey and China. Our phylogenetic analysis of Vssc unequivocally supports the hypothesis of multiple independent origins of kdr, super-kdr and kdr-his on an unprecedented geographic scale. The implications of these evolutionary processes on pest management are discussed.

  2. Resolution of multiple sheet-type structures in self-potential measurement

    Indian Academy of Sciences (India)

    Arkoprovo Biswas; Shashi Prakash Sharma

    2014-06-01

    The resolution of self-potential anomalies due to closely spaced multiple sheet-like bodies by the potential difference and potential gradient is studied in this paper. Self-potential anomalies due to several synthetic models were inverted through a very fast simulated annealing (VFSA) global optimization. Increase in depth to the top, polarization constant and depth extent of the body decreases resolution at a particular target separation. It has been observed that depth to the top and separation between two targets play an important role in the resolution. Vertical sheets at equal depth can be resolved in the potential difference measurement only if they are separated by at least four times their depth, while they can be resolved in the gradient method, if they are separated by twice the depth. Resolution using potential difference becomes more difficult for dipping sheets, although the potential gradient method can resolve them efficiently. Efficacy of potential gradient data in the inversion is demonstrated in the study using synthetic data as well as field measurement from South Purulia Shear Zone related with uranium investigation.

  3. Imaging Surrogates of Disease Activity in Neuromyelitis Optica Allow Distinction from Multiple Sclerosis.

    Science.gov (United States)

    Matthews, Lucy; Kolind, Shannon; Brazier, Alix; Leite, Maria Isabel; Brooks, Jonathan; Traboulsee, Anthony; Jenkinson, Mark; Johansen-Berg, Heidi; Palace, Jacqueline

    2015-01-01

    Inflammatory demyelinating lesions of the central nervous system are a common feature of both neuromyelitis optica and multiple sclerosis. Despite this similarity, it is evident clinically that the accumulation of disability in patients with neuromyelitis optica is relapse related and that a progressive phase is very uncommon. This poses the question whether there is any pathological evidence of disease activity or neurodegeneration in neuromyelitis optica between relapses. To investigate this we conducted a longitudinal advanced MRI study of the brain and spinal cord in neuromyelitis optica patients, comparing to patients with multiple sclerosis and controls. We found both cross-sectional and longitudinal evidence of diffusely distributed neurodegenerative surrogates in the multiple sclerosis group (including thalamic atrophy, cervical cord atrophy and progressive widespread diffusion and myelin water imaging abnormalities in the normal appearing white matter) but not in those with neuromyelitis optica, where localised abnormalities in the optic radiations of those with severe visual impairment were noted. In addition, between relapses, there were no new silent brain lesions in the neuromyelitis optica group. These findings indicate that global central nervous system neurodegeneration is not a feature of neuromyelitis optica. The work also questions the theory that neurodegeneration in multiple sclerosis is a chronic sequela to prior inflammatory and demyelinating pathology, as this has not been found to be the case in neuromyelitis optica where the lesions are often more destructive.

  4. Imaging Surrogates of Disease Activity in Neuromyelitis Optica Allow Distinction from Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Lucy Matthews

    Full Text Available Inflammatory demyelinating lesions of the central nervous system are a common feature of both neuromyelitis optica and multiple sclerosis. Despite this similarity, it is evident clinically that the accumulation of disability in patients with neuromyelitis optica is relapse related and that a progressive phase is very uncommon. This poses the question whether there is any pathological evidence of disease activity or neurodegeneration in neuromyelitis optica between relapses. To investigate this we conducted a longitudinal advanced MRI study of the brain and spinal cord in neuromyelitis optica patients, comparing to patients with multiple sclerosis and controls. We found both cross-sectional and longitudinal evidence of diffusely distributed neurodegenerative surrogates in the multiple sclerosis group (including thalamic atrophy, cervical cord atrophy and progressive widespread diffusion and myelin water imaging abnormalities in the normal appearing white matter but not in those with neuromyelitis optica, where localised abnormalities in the optic radiations of those with severe visual impairment were noted. In addition, between relapses, there were no new silent brain lesions in the neuromyelitis optica group. These findings indicate that global central nervous system neurodegeneration is not a feature of neuromyelitis optica. The work also questions the theory that neurodegeneration in multiple sclerosis is a chronic sequela to prior inflammatory and demyelinating pathology, as this has not been found to be the case in neuromyelitis optica where the lesions are often more destructive.

  5. 77 FR 60124 - Draft Guidance for Industry on Initial Completeness Assessments for Type II Active Pharmaceutical...

    Science.gov (United States)

    2012-10-02

    ... Assessments for Type II Active Pharmaceutical Ingredient Drug Master Files Under the Generic Drug User Fee... Amendments of 2012 (GDUFA), holders of certain drug master files, namely, Type II active...

  6. Mental Health in Multiple Sclerosis Patients without Limitation of Physical Function: The Role of Physical Activity

    Directory of Open Access Journals (Sweden)

    Alexander Tallner

    2015-07-01

    Full Text Available Multiple sclerosis (MS patients, in general, show reduced physical function, physical activity, and quality of life. Positive associations between physical activity and quality of life have been reported. In particular, we were interested in the relation between physical activity and mental health in MS patients without limitation of physical function, since limitations of physical function may influence both physical activity and quality of life. Assessment comprised the Baecke questionnaire on physical activity, the Short Form 36 Health Survey (SF-36, and Beck Depression Inventory (BDI. We ranked our sample according to physical activity into four groups and performed an ANOVA to analyze the relationship between levels of physical activity and health-related quality of life (HRQoL. Then we performed a subgroup analysis and included patients with unlimited walking distance and a score of less than 18 in the BDI. Most active vs. inactive patients were compared for the mental subscales of the SF-36 and depression scores. From 632 patients, 265 met inclusion criteria and hence quartiles were filled with 67 patients each. Active and inactive patients did not differ considerably in physical function. In contrast, mental subscales of the SF-36 were higher in active patients. Remarkable and significant differences were found regarding vitality, general health perception, social functioning and mental health, all in favor of physically active patients. Our study showed that higher physical activity is still associated with higher mental health scores even if limitations of physical function are accounted for. Therefore, we believe that physical activity and exercise have considerable health benefits for MS patients.

  7. Mental Health in Multiple Sclerosis Patients without Limitation of Physical Function: The Role of Physical Activity.

    Science.gov (United States)

    Tallner, Alexander; Waschbisch, Anne; Hentschke, Christian; Pfeifer, Klaus; Mäurer, Mathias

    2015-07-02

    Multiple sclerosis (MS) patients, in general, show reduced physical function, physical activity, and quality of life. Positive associations between physical activity and quality of life have been reported. In particular, we were interested in the relation between physical activity and mental health in MS patients without limitation of physical function, since limitations of physical function may influence both physical activity and quality of life. Assessment comprised the Baecke questionnaire on physical activity, the Short Form 36 Health Survey (SF-36), and Beck Depression Inventory (BDI). We ranked our sample according to physical activity into four groups and performed an ANOVA to analyze the relationship between levels of physical activity and health-related quality of life (HRQoL). Then we performed a subgroup analysis and included patients with unlimited walking distance and a score of less than 18 in the BDI. Most active vs. inactive patients were compared for the mental subscales of the SF-36 and depression scores. From 632 patients, 265 met inclusion criteria and hence quartiles were filled with 67 patients each. Active and inactive patients did not differ considerably in physical function. In contrast, mental subscales of the SF-36 were higher in active patients. Remarkable and significant differences were found regarding vitality, general health perception, social functioning and mental health, all in favor of physically active patients. Our study showed that higher physical activity is still associated with higher mental health scores even if limitations of physical function are accounted for. Therefore, we believe that physical activity and exercise have considerable health benefits for MS patients.

  8. Target intervention against multiple-risk markers to reduce cardiovascular disease in patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Gaede, Peter; Pedersen, Oluf

    2004-01-01

    The risk of cardiovascular disease is markedly increased in patients with type 2 diabetes with a prevalence twice as high compared to the background population. With the recognition of multiple concomitant risk factors for both microvascular as well as cardiovascular disease in type 2 diabetic...... factors for cardiovascular disease is capable of reducing the risk for a combined endpoint of cardiovascular mortality, non-fatal myocardial infarction, non-fatal stroke, coronary interventions, revascularisation to legs, and amputations by 50%....... patients, treatment strategies have changed during recent years. This review focuses on the many recent drug trials that have set the course for an effective multifactorial treatment of the disease. Thus, the Steno-2 Study has shown that an intensified multifactorial intervention targeting several risk...

  9. Mapping of Variable DNA Methylation Across Multiple Cell Types Defines a Dynamic Regulatory Landscape of the Human Genome

    Science.gov (United States)

    Gu, Junchen; Stevens, Michael; Xing, Xiaoyun; Li, Daofeng; Zhang, Bo; Payton, Jacqueline E.; Oltz, Eugene M.; Jarvis, James N.; Jiang, Kaiyu; Cicero, Theodore; Costello, Joseph F.; Wang, Ting

    2016-01-01

    DNA methylation is an important epigenetic modification involved in many biological processes and diseases. Many studies have mapped DNA methylation changes associated with embryogenesis, cell differentiation, and cancer at a genome-wide scale. Our understanding of genome-wide DNA methylation changes in a developmental or disease-related context has been steadily growing. However, the investigation of which CpGs are variably methylated in different normal cell or tissue types is still limited. Here, we present an in-depth analysis of 54 single-CpG-resolution DNA methylomes of normal human cell types by integrating high-throughput sequencing-based methylation data. We found that the ratio of methylated to unmethylated CpGs is relatively constant regardless of cell type. However, which CpGs made up the unmethylated complement was cell-type specific. We categorized the 26,000,000 human autosomal CpGs based on their methylation levels across multiple cell types to identify variably methylated CpGs and found that 22.6% exhibited variable DNA methylation. These variably methylated CpGs formed 660,000 variably methylated regions (VMRs), encompassing 11% of the genome. By integrating a multitude of genomic data, we found that VMRs enrich for histone modifications indicative of enhancers, suggesting their role as regulatory elements marking cell type specificity. VMRs enriched for transcription factor binding sites in a tissue-dependent manner. Importantly, they enriched for GWAS variants, suggesting that VMRs could potentially be implicated in disease and complex traits. Taken together, our results highlight the link between CpG methylation variation, genetic variation, and disease risk for many human cell types. PMID:26888867

  10. Psychedelics Recruit Multiple Cellular Types and Produce Complex Transcriptional Responses Within the Brain

    OpenAIRE

    Martin, David A.; Nichols, Charles D.

    2016-01-01

    There has recently been a resurgence of interest in psychedelics, substances that profoundly alter perception and cognition and have recently demonstrated therapeutic efficacy to treat anxiety, depression, and addiction in the clinic. The receptor mechanisms that drive their molecular and behavioral effects involve activation of cortical serotonin 5-HT2A receptors, but the responses of specific cellular populations remain unknown. Here, we provide evidence that a small subset of 5-HT2A-expres...

  11. Multiple orthogonal polynomials of mixed type: Gauss-Borel factorization and the multi-component 2D Toda hierarchy

    CERN Document Server

    Álvarez-Fernández, Carlos; Mañas, Manuel

    2010-01-01

    Multiple orthogonality is considered in the realm of a Gauss-Borel factorization problem for a semi-infinite moment matrix. Perfect combinations of weights and a finite Borel measure are constructed in terms of M-Nikishin systems. These perfect combinations ensure that the problem of mixed multiple orthogonality has a unique solution, that can be obtained from the solution to a Gauss-Borel factorization problem for a semi-infinite matrix, which plays the role of a moment matrix. This leads to sequences of multiple orthogonal polynomials, their duals and second kind functions. It also gives the corresponding linear forms that are bi-orthogonal to the dual linear forms. Expressions for these objects in terms of determinants from the moment matrix are given, recursion relations are found, which imply a multi-diagonal Jacobi type matrix with double staircase shape, and results like the ABC theorem or the Christoffel-Darboux formula are re-derived in this context (using the factorization problem and the generalize...

  12. Human fetal islet transplantation in type 1 diabetic patients: comparison of metabolic effects between single and multiple implantation regimens.

    Science.gov (United States)

    Djordjevic, P B; Lalic, N M; Jotic, A; Paunovic, I; Lalic, K; Raketic, N; Nikolic, D; Zamaklar, M; Rajkovic, N; Lukic, L; Dimitrijevic-Sreckovic, V; Dragasevic, M; Nikolic, D; Markovic, I

    2004-11-01

    Previous studies suggest that multiple transplantations might be equally efficient to a single regimen for human adult islets. The aim of this study was to compare metabolic parameters after each of the two regimens of human fetal islet (HFI) transplantation in type 1 diabetics. In group A (single transplant, n = 9), 180 +/- 20 x 1000 HFI equivalents (IEQs) were implanted by a single IM injection; in group B (multiple transplants, n = 8) islets were implanted as three consecutive injections (60 +/- 10 x 1000 IEQs) at 7-day intervals. We analyzed the metabolic parameters on days -1, 30, 60, 90, 120, 150, and 180 after the procedure. Among the metabolic parameters, we evaluated insulin secretion capacity-ISC (C peptide, RIA), metabolic control (HbA1c, chromatography), and insulin daily dose IDD. We found that C peptide levels increased, peaking on day 90 (A: 0.38 +/- 0.15; B: 0.34 +/- 0.19 nmol/L, P = NS) and then rapidly decreasing without differences, the HbA1c levels and IDD decreased in the same manner without differences between the groups. Our results demonstrate that multiple and single islet transplant regimens are equally efficient to temporarily restore a significant ISC with improvement of metabolic and clinical parameters. The results imply that the two regimens have an equal clinical value.

  13. Materials design data for reduced activation martensitic steel type EUROFER

    Science.gov (United States)

    Tavassoli, A.-A. F.; Alamo, A.; Bedel, L.; Forest, L.; Gentzbittel, J.-M.; Rensman, J.-W.; Diegele, E.; Lindau, R.; Schirra, M.; Schmitt, R.; Schneider, H. C.; Petersen, C.; Lancha, A.-M.; Fernandez, P.; Filacchioni, G.; Maday, M. F.; Mergia, K.; Boukos, N.; Baluc; Spätig, P.; Alves, E.; Lucon, E.

    2004-08-01

    Materials design limits derived so far from the data generated in Europe for the reduced activation ferritic/martensitic (RAFM) steel type Eurofer are presented. These data address the short-term needs of the ITER Test Blanket Modules and a DEMOnstration fusion reactor. Products tested include plates, bars, tubes, TIG and EB welds, as well as powder consolidated blocks and solid-solid HIP joints. Effects of thermal ageing and low dose neutron irradiation are also included. Results are sorted and screened according to design code requirements before being introduced in reference databases. From the physical properties databases, variations of magnetic properties, modulus of elasticity, density, thermal conductivity, thermal diffusivity, specific heat, mean and instantaneous linear coefficients of thermal expansion versus temperature are derived. From the tensile and creep properties databases design allowable stresses are derived. From the instrumented Charpy impact and fracture toughness databases, ductile to brittle transition temperature, toughness and behavior of materials in different fracture modes are evaluated. From the fatigue database, total strain range versus number of cycles to failure curves are plotted and used to derive fatigue design curves. Cyclic curves are also derived and compared with monotonic hardening curves. Finally, irradiated and aged materials data are compared to ensure that the safety margins incorporated in unirradiated design limits are not exceeded.

  14. Molecular advances in plasminogen activator inhibitor 1 interaction with thrombin and tissue-type plasminogen activator.

    Science.gov (United States)

    Stoop, A; van Meijer, M; Horrevoets, A J; Pannekoek, H

    1997-02-01

    Plasminogen activator inhibitor 1 (PAI-1) is a glycoprotein that controls the activity of the key enzymes of the fibrinolytic system, the serine proteases tissue-type plasminogen activator (t-PA) and urokinase-type plasminogen activator (u-PA). Inhibition is accomplished by rapid formation of inactive, equimolar PAI-1/PA complexes. The physiological importance of PAI-1 for the fibrinolytic system has been underscored by the observation that in humans, a homozygous defect results in hemorrhagic episodes. In addition to its function in surveillance of the integrity of clots, PAI-1 efficiently inhibits the serine protease thrombin in vitro, provided that either the high molecular weight glycosaminoglycan heparin or the glycoprotein vitronectin is present. These cofactors accelerate the rate of thrombin inhibition by PAI-1 by more than two orders of magnitude. Inhibition of thrombin by PAI-1 proceeds according to a "suicide substrate mechanism," typified by a branched reaction pathway, leading either to stable PAI-1/thrombin complexes or to degradation of the inhibitor and recycling of enzyme. The cofactors heparin and vitronectin, although increasing inhibition through different mechanisms, essentially promote PAI-1 degradation by thrombin. In view of the multitude of functions attributed to thrombin, the authors propose that the relevance of thrombin inhibition by PAI-1 is to restrict its mitogenic activity, rather than to affect its coagulation function in plasma. (Trends Cardiovasc Med 1997;7:47-51). © 1997, Elsevier Science Inc.

  15. Activity deprivation induces neuronal cell death: mediation by tissue-type plasminogen activator.

    Directory of Open Access Journals (Sweden)

    Eldi Schonfeld-Dado

    Full Text Available Spontaneous activity is an essential attribute of neuronal networks and plays a critical role in their development and maintenance. Upon blockade of activity with tetrodotoxin (TTX, neurons degenerate slowly and die in a manner resembling neurodegenerative diseases-induced neuronal cell death. The molecular cascade leading to this type of slow cell death is not entirely clear. Primary post-natal cortical neurons were exposed to TTX for up to two weeks, followed by molecular, biochemical and immunefluorescence analysis. The expression of the neuronal marker, neuron specific enolase (NSE, was down-regulated, as expected, but surprisingly, there was a concomitant and striking elevation in expression of tissue-type plasminogen activator (tPA. Immunofluorescence analysis indicated that tPA was highly elevated inside affected neurons. Transfection of an endogenous tPA inhibitor, plasminogen activator inhibitor-1 (PAI-1, protected the TTX-exposed neurons from dying. These results indicate that tPA is a pivotal player in slowly progressing activity deprivation-induced neurodegeneration.

  16. Findings of Optical Coherence Tomography of Retinal Nerve Fiber Layer in Two Common Types of Multiple Sclerosis.

    Science.gov (United States)

    Yousefipour, Gholamali; Hashemzahi, Zabihollah; Yasemi, Masood; Jahani, Pegah

    2016-06-01

    Multiple sclerosis (MS) is the most prevalent disease caused by the inflammatory demyelinating process that causes progressive nervous system degeneration over the time. Optical Coherence Tomography (OCT) is a non-invasive optical imaging technology, which can measure the thickness of retinal nerve fiber layer as well as the diameter of the macula. The purpose of the study is evaluation OCT findings in two common types of multiple sclerosis. For doing the cross-sectional study, 63 patients with two prevalent types of multiple sclerosis (35 patients with Relapse Remitting Multiple Sclerosis (RRMS) and 28 patients with Secondary Progressive Multiple Sclerosis (SPMS) were evaluated for 6 months. Exclusion criteria of the study were a history of optic neuritis, suffering from diabetes mellitus, hypertension, ocular disease, and the presence of other neurologic degenerative diseases. Then, the thickness of retinal nerve fiber layer (RNFL), as well as thickness and volume of the macula, were measured in the patients using OCT technology. The disability rate of patients was evaluated according to Expanded Disability Status Scale (EDSS). Finally, data was analyzed by means of SPSS software. Overall, 35 patients with RRMS (with mean age of 32.37+10.01, average disease period of 3.81+3.42 and mean EDSS of 1.84+0.45) and 28 patients with SPMS (with mean age of 39.21+9.33, average disease period of 11.32+5.87 and mean EDSS of 5.12+1.46) were assessed and compared in terms of retinal nerve fiber layer and size and thickness of macula. In all of these sections, the thicknesses were smaller in SPMS patients than patients with RRMS. But, there was a significant difference in total thickness (81.82µm versus 96.03µm with P=0.04) and thickness of temporal sector (54.5 µm versus 69.34 µm with P=0.04) of retinal nerve fiber layer and macular size at the superior sector of external ring (1.48 mm³ versus 1.58 mm³ with P=0.03), and nasal sector of external ring surrounding macula (1

  17. Findings of Optical Coherence Tomography of Retinal Nerve Fiber Layer in Two Common Types of Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Gholamali Yousefipour

    2016-06-01

    Full Text Available Multiple sclerosis (MS is the most prevalent disease caused by the inflammatory demyelinating process that causes progressive nervous system degeneration over the time. Optical Coherence Tomography (OCT is a non-invasive optical imaging technology, which can measure the thickness of retinal nerve fiber layer as well as the diameter of the macula. The purpose of the study is evaluation OCT findings in two common types of multiple sclerosis. For doing the cross-sectional study, 63 patients with two prevalent types of multiple sclerosis (35 patients with Relapse Remitting Multiple Sclerosis (RRMS and 28 patients with Secondary Progressive Multiple Sclerosis (SPMS were evaluated for 6 months. Exclusion criteria of the study were a history of optic neuritis, suffering from diabetes mellitus, hypertension, ocular disease, and the presence of other neurologic degenerative diseases. Then, the thickness of retinal nerve fiber layer (RNFL, as well as thickness and volume of the macula, were measured in the patients using OCT technology. The disability rate of patients was evaluated according to Expanded Disability Status Scale (EDSS. Finally, data was analyzed by means of SPSS software. Overall, 35 patients with RRMS (with mean age of 32.37+10.01, average disease period of 3.81+3.42 and mean EDSS of 1.84+0.45 and 28 patients with SPMS (with mean age of 39.21+9.33, average disease period of 11.32+5.87 and mean EDSS of 5.12+1.46 were assessed and compared in terms of retinal nerve fiber layer and size and thickness of macula. In all of these sections, the thicknesses were smaller in SPMS patients than patients with RRMS. But, there was a significant difference in total thickness (81.82µm versus 96.03µm with P=0.04 and thickness of temporal sector (54.5 µm versus 69.34 µm with P=0.04 of retinal nerve fiber layer and macular size at the superior sector of external ring (1.48 mm³ versus 1.58 mm³ with P=0.03, and nasal sector of external ring surrounding

  18. Solar Distillation System Based on Multiple-Effect Diffusion Type Still

    Directory of Open Access Journals (Sweden)

    Bin-Juine Huang

    2014-03-01

    Full Text Available The present study intends to develop a high-performance solar-assisted desalination system (SADS using multi-effect diffusion type still (MEDS and the vacuum tube solar collector (VTSC. A MEDS prototype was designed and built. The measured result is very close to the estimation. The 10-effect MEDS will produce pure water at about 13.7 L/day/m2 collector area at a solar irradiation of 600 W/m2 and 19.7 L/day/m2 collector area at solar irradiation 800 W/m2. For 20-effect still, the yield rate increase is 32% compared to 10-effect still.

  19. Heat Transfer in a Fin-Tube Type Heat Exchanger with Multiple Inlet Ports

    Science.gov (United States)

    Umekawa, Hisashi; Ozawa, Mamoru; Kawamoto, Akira; Takifuji, Tomonori; Kataoka, Masaki

    Numerical simulation of gas flow in a fin-tube type heat exchanger model has been conducted. The simulation model is two-dimensional and has three inlet ports at the lower boundary and one exit port at the upper boundary. The flow field is partitioned into several sub-channels by spacers. In order to realize the uniform temperature distribution at the exit port and relatively uniform heat transfer rate among the spacers,It is necessary to arrange so that the higher temperature fluid is injected from center port at lower velocity and the lower temperature fluid is injected from both side ports at higher velocity. The thermal flow visualization experiment with thermosensitive liquid-crystal sheet has confirmed the simulation results.

  20. Multiple reflection-asymmetric-type band structures in {sup 220}Th and dinuclear model

    Energy Technology Data Exchange (ETDEWEB)

    Shneidman, T.M.; Adamian, G.G.; Antonenko, N.V.; Jolos, R.V. [Joint Institute for Nuclear Research, Dubna (Russian Federation); Scheid, W. [Institut fuer Theoretische Physik der Justus-Liebig-Universitaet, Giessen (Germany)

    2011-03-15

    The negative-parity bands with different values of K in {sup 220}Th are analysed within the dinuclear system model which was previously used for describing the ground-state alternating-parity bands with K = 0 in deformed actinides. The model is based on the assumption that the cluster type shapes are produced by the collective motion in the mass-asymmetry coordinate. To describe the reflection-asymmetric collective modes characterized by the nonzero values of K, the intrinsic excitations of clusters are taken into account. The observed excitation spectrum, angular-momentum dependence of the parity splitting and the staggering behaviour of the B(E1)/B(E2) ratios are explained. (orig.)

  1. Multiple Behavior Change in Diet and Activity: A Randomized Controlled Trial Using Mobile Technology

    Science.gov (United States)

    Spring, Bonnie; Schneider, Kristin; McFadden, H.G.; Vaughn, Jocelyn; Kozak, Andrea T.; Smith, Malaina; Moller, Arlen C.; Epstein, Leonard H.; DeMott, Andrew; Hedeker, Donald; Siddique, Juned; Lloyd-Jones, Donald M.

    2012-01-01

    Background Many patients exhibit multiple chronic disease risk behaviors. Research provides little information about advice that can maximize simultaneous health behavior changes. Methods To test which combination of diet and activity advice maximizes healthy change, we randomized 204 adults with elevated saturated fat and low fruit/vegetable intakes, high sedentary leisure time and low physical activity to one of four treatments: increase fruit/vegetable and physical activity; decrease fat and sedentary leisure; decrease fat and increase physical activity; increase fruit/vegetable and decrease sedentary leisure. Treatments provided three weeks of remote coaching supported by mobile decision support technology and financial incentives. During treatment, incentives were contingent on using the mobile device to self-monitor and attain behavioral targets; during follow-up they were contingent only on recording. The outcome was standardized, composite improvement on the four diet and activity behaviors at end of treatment and five month follow-up. Results Of those randomized, 200 (98%) completed follow-up. The increase fruit/vegetable and decrease sedentary leisure treatment improved more than the other 3 treatments (p<.001). Specifically, fruit/vegetables increased from 1.2 servings/day to 5.5; sedentary leisure decreased from 219.2 minutes/day to 89.3; saturated fat decreased from 12.0% of calories consumed to 9.5%. Differences between treatment groups were maintained through follow-up. Traditional dieting (decrease fat and increase physical activity) improved less than the other 3 treatments (p<.001). Conclusions Remote coaching supported by mobile technology and financial incentives holds promise to improve diet and activity. Targeting fruits/vegetables and sedentary leisure together maximizes overall adoption and maintenance of multiple healthy behavior changes. PMID:22636824

  2. Morphological characterization and topographic analysis of multiple photoreceptor types in the retinae of mesopelagic hatchetfishes with tubular eyes

    Directory of Open Access Journals (Sweden)

    Lauren Michelle Biagioni

    2016-03-01

    Full Text Available Marine hatchetfishes, Argyropelecus spp., are one of the 14 genera of mesopelagic teleosts, which possess tubular eyes. The tubular eyes are positioned dorsally on the head and consist of a main retina, which subtends a large dorsal binocular field, and an accessory retina, which subtends the lateral monocular visual field. The topographic distribution of photoreceptors in the retina of Argyropelecus sladeni, A. affinis and A. aculeatus was determined using a random, unbiased and systematic stereological approach, which consistently revealed a region of high density (area centralis in the central region of the main retina (up to a peak of 96,000 receptors per mm2 and a relatively homogeneous density of photoreceptors in the accessory retina (of approximately 20,000 receptors per mm2. The position of the area centralis in the main retina indicates this retinal region subserves greater spatial resolution in the centre of the dorsal binocular visual field. Light microscopy and transmission electron microscopy also revealed the presence of multiple photoreceptor types (two rod-like and one cone-like based on the size and shape of the inner and outer segments and ultrastructural differences in the ellipsoidal region. The presence of multiple photoreceptor types in these tubular-eyed, mesopelagic hatchetfishes may reflect the need for the visual system to function under different lighting conditions during vertical migratory behavior, especially given their unique dorsally-facing eyes.

  3. Chemokine Receptor CCR5 Δ32 Genetic Analysis Using Multiple Specimen Types and the NucliSens Basic Kit†

    Science.gov (United States)

    Tetali, Suryakumari; Lee, Eun Mi; Kaplan, Mark H.; Romano, Joseph W.; Ginocchio, Christine C.

    2001-01-01

    Resistance to HIV-1 infection and delayed disease progression have been associated with a 32-bp deletion (Δ32) in the gene encoding the CCR5 chemokine receptor. In the present study we describe the modification of a nucleic acid sequence-based amplification (NASBA)-based CCR5 genotyping assay for a NucliSens Basic Kit (Organon Teknika, Durham, N.C.) format using a new target-specific sandwich oligonucleotide detection methodology. The new method permitted the use of generic electrochemiluminescent probes supplied in the NucliSens Basic Kit, whereas the original NASBA method required expensive target-specific ruthenium detection probes. The Basic Kit CCR5 Δ32 genotypic analysis was in 100% concordance with both the original NASBA assay and DNA PCR results. This study also evaluated the use of multiple specimen types, including peripheral blood mononuclear cells (PBMC), whole blood, dried blood spots, buccal scrapings, and plasma, for CCR5 genotype analysis. The sensitivities of the three assays were comparable when PBMC or whole blood was the specimen source. In contrast, when dried blood spots, buccal scrapings, or plasma was used as the sample source, the sensitivity of DNA PCR was 80.95, 42.8, or 0%, respectively, compared to 100% sensitivity obtained with the original NASBA and Basic Kit NASBA assays. Our study indicates that the NucliSens Basic Kit NASBA assay is very sensitive and specific for CCR5 Δ32 genotyping using multiple sample types. PMID:11527812

  4. Chemokine receptor CCR5 Delta 32 genetic analysis using multiple specimen types and the NucliSens Basic Kit.

    Science.gov (United States)

    Tetali, S; Lee, E M; Kaplan, M H; Romano, J W; Ginocchio, C C

    2001-09-01

    Resistance to HIV-1 infection and delayed disease progression have been associated with a 32-bp deletion (Delta32) in the gene encoding the CCR5 chemokine receptor. In the present study we describe the modification of a nucleic acid sequence-based amplification (NASBA)-based CCR5 genotyping assay for a NucliSens Basic Kit (Organon Teknika, Durham, N.C.) format using a new target-specific sandwich oligonucleotide detection methodology. The new method permitted the use of generic electrochemiluminescent probes supplied in the NucliSens Basic Kit, whereas the original NASBA method required expensive target-specific ruthenium detection probes. The Basic Kit CCR5 Delta32 genotypic analysis was in 100% concordance with both the original NASBA assay and DNA PCR results. This study also evaluated the use of multiple specimen types, including peripheral blood mononuclear cells (PBMC), whole blood, dried blood spots, buccal scrapings, and plasma, for CCR5 genotype analysis. The sensitivities of the three assays were comparable when PBMC or whole blood was the specimen source. In contrast, when dried blood spots, buccal scrapings, or plasma was used as the sample source, the sensitivity of DNA PCR was 80.95, 42.8, or 0%, respectively, compared to 100% sensitivity obtained with the original NASBA and Basic Kit NASBA assays. Our study indicates that the NucliSens Basic Kit NASBA assay is very sensitive and specific for CCR5 Delta32 genotyping using multiple sample types.

  5. Use of Multiple Reheat Helium Brayton Cycles to Eliminate the Intermediate Heat Transfer Loop for Advanced Loop Type SFRs

    Energy Technology Data Exchange (ETDEWEB)

    Haihua Zhao; Hongbin Zhang; Samuel E. Bays

    2009-05-01

    The sodium intermediate heat transfer loop is used in existing sodium cooled fast reactor (SFR) plant design as a necessary safety measure to separate the radioactive primary loop sodium from the water of the steam Rankine power cycle. However, the intermediate heat transfer loop significantly increases the SFR plant cost and decreases the plant reliability due to the relatively high possibility of sodium leakage. A previous study shows that helium Brayton cycles with multiple reheat and intercooling for SFRs with reactor outlet temperature in the range of 510°C to 650°C can achieve thermal efficiencies comparable to or higher than steam cycles or recently proposed supercritical CO2 cycles. Use of inert helium as the power conversion working fluid provides major advantages over steam or CO2 by removing the requirement for safety systems to prevent and mitigate the sodium-water or sodium-CO2 reactions. A helium Brayton cycle power conversion system therefore makes the elimination of the intermediate heat transfer loop possible. This paper presents a pre-conceptual design of multiple reheat helium Brayton cycle for an advanced loop type SFR. This design widely refers the new horizontal shaft distributed PBMR helium power conversion design features. For a loop type SFR with reactor outlet temperature 550°C, the design achieves 42.4% thermal efficiency with favorable power density comparing with high temperature gas cooled reactors.

  6. Peroxisome proliferator-activated receptors as molecular targets in relation to obesity and type 2 diabetes.

    Science.gov (United States)

    Seda, Ondørej; Sedová, Lucie

    2007-06-01

    The three isotypes of peroxisome proliferator-activated receptors (PPARs) are currently perceived as major regulatory nodes (or hubs) of metabolic pathway networks, linking most prevalent diseases including Type 2 diabetes, obesity, dyslipidemia and atherosclerosis. The integrative functions of PPARs are also reflected in their ecogenetic profile, when the variants underlying pharmacogenetic interactions were also shown to modulate the effect of lifestyle factors. Despite their extensive clinical use, there are many outstanding issues, especially concerning their safety. Critical pharmacogenomic assessment is warranted for the new potent ligands of multiple PPAR isoforms as many have displayed serious side-effects in a limited number of treated subjects. Nevertheless, the advent of genomic, transcriptomic and system biology-level approaches, integrating knowledge from model systems and human biology, should greatly facilitate the transition to individualized PPAR-based therapies.

  7. Cdk4 functions in multiple cell types to control Drosophila intestinal stem cell proliferation and differentiation

    Directory of Open Access Journals (Sweden)

    Mojca Adlesic

    2016-03-01

    Full Text Available The proliferation of intestinal stem cells (ISCs and differentiation of enteroblasts to form mature enteroendocrine cells and enterocytes in the Drosophila intestinal epithelium must be tightly regulated to maintain homeostasis. We show that genetic modulation of CyclinD/Cdk4 activity or mTOR-dependent signalling cell-autonomously regulates enterocyte growth, which influences ISC proliferation and enteroblast differentiation. Increased enterocyte growth results in higher numbers of ISCs and defective enterocyte growth reduces ISC abundance and proliferation in the midgut. Adult midguts deficient for Cdk4 show severe disruption of intestinal homeostasis characterised by decreased ISC self-renewal, enteroblast differentiation defects and low enteroendocrine cell and enterocyte numbers. The ISC/enteroblast phenotypes result from a combination of cell autonomous and non-autonomous requirements for Cdk4 function. One non-autonomous consequence of Cdk4-dependent deficient enterocyte growth is high expression of Delta in ISCs and Delta retention in enteroblasts. We postulate that aberrant activation of the Delta–Notch pathway is a possible partial cause of lost ISC stemness. These results support the idea that enterocytes contribute to a putative stem cell niche that maintains intestinal homeostasis in the Drosophila anterior midgut.

  8. Iron K$\\alpha$ emission in type-I and type-II Active Galactic Nuclei

    CERN Document Server

    Ricci, Claudio; Paltani, Stephane; Ichikawa, Kohei; Gandhi, Poshak; Awaki, Hisamitsu

    2014-01-01

    The narrow Fe K$\\alpha$ line is one of the main signatures of the reprocessing of X-ray radiation from the material surrounding supermassive black holes, and it has been found to be omnipresent in the X-ray spectra of active galactic nuclei (AGN). In this work we study the characteristics of the narrow Fe K$\\alpha$ line in different types of AGN. Using the results of a large Suzaku study we find that Seyfert 2s have on average lower Fe K$\\alpha$ luminosities than Seyfert 1s for the same 10-50 keV continuum luminosity. Simulating dummy Sy1s and Sy2s populations using physical torus models of X-ray reflected emission, we find that this difference can be explained by means of different average inclination angles with respect to the torus, as predicted by the unified model. Alternative explanations include differences in the intensities of Compton humps or in the photon index distributions. We show that the ratio between the flux of the broad and narrow Fe K$\\alpha$ line in the 6.35-6.45 keV range depends on the ...

  9. Indoleamine 2,3 Dioxygenase (IDO Expression and Activity in Relapsing-Remitting Multiple Sclerosis.

    Directory of Open Access Journals (Sweden)

    Roberta Mancuso

    Full Text Available Interferon gamma (IFN-γ production induces the transcription of indoleamine 2,3 dioxygenase (IDO resulting in the reduction of T-cell activation and proliferation through the depletion of tryptophan and the elicitation of Treg lymphocytes. IDO was shown to be involved in the pathogenesis of autoimmune diseases; we investigated whether changes in IDO gene expression and activity could be indicative of onset of relapse in multiple sclerosis (MS patients.IDO and interferon-γ (IFN-γ gene expression, serum IDO activity (Kynurenine/Tryptophan ratio and serum neopterin concentration--a protein released by macrophages upon IFN-γ stimulation--were measured in 51 individuals: 36 relapsing remitting (RR-MS patients (21 in acute phase--AMS, 15 in stable phase--SMS and 15 healthy controls (HC. PBMCs samples in AMS patients were collected before (BT-AMS and during glucocorticoids-based therapy (DT-AMS.IDO expression was increased and IFN-γ was decreased (p<0.001 in BT-AMS compared to SMS patients. Glucocorticoids-induced disease remission resulted in a significant reduction of IDO and IFN-γ gene expression, IDO catalytic activity (p<0.001. Serum neopterin concentration followed the same trend as IDO expression and activity.Measurement of IDO gene expression and activity in blood could be a useful marker to monitor the clinical course of RR-MS. Therapeutic interventions modulating IDO activity may be beneficial in MS.

  10. Supercal: Cross-Calibration of Multiple Photometric Systems to Improve Cosmological Measurements with Type Ia Supernovae

    CERN Document Server

    Scolnic, D; Riess, A G; Rest, A; Schlafly, E; Foley, R J; Finkbeiner, D; Tang, C; Burgett, W S; Chambers, K C; Draper, P W; Hodapp, K W; Huber, M E; Kaiser, N; Kudritzki, R P; Magnier, E A; Metcalfe, N; Stubbs, C W

    2015-01-01

    Current cosmological analyses which use Type Ia supernova (SN Ia) observations combine SN samples to expand the redshift range beyond that of a single sample and increase the overall sample size. The inhomogeneous photometric calibration between different SN samples is one of the largest systematic uncertainties of the cosmological parameter estimation. To place these different samples on a single system, analyses currently use observations of a small sample of very bright flux standards on the $HST$ system. We propose a complementary method, called `Supercal', in which we use measurements of secondary standards in each system, compare these to measurements of the same stars in the Pan-STARRS1 (PS1) system, and determine offsets for each system relative to PS1, placing all SN observations on a single, consistent photometric system. PS1 has observed $3\\pi$ of the sky and has a relative calibration of better than 5 mmag (for $\\sim15

  11. Multiple effects of consonant manner of articulation and intonation type on F0 in English

    Science.gov (United States)

    Xu, Yi; Wallace, Andrew

    2001-05-01

    In this study we examine how consonant manner of articulation interacts with intonation type in shaping the F0 contours in English. Native speakers of American English read aloud words differing in vowel length, consonant manner of articulation and consonant position in word. They produced each word in either a statement or question carrier. F0 contours of their speech were extracted by measuring every complete vocal period. Preliminary results based on graphic analysis of three speakers' data suggest that there are three distinct consonantal effects: F0 interruption due to devoicing, a large but brief (10-40 ms) F0 raising at the onset of voicing, and a smaller but longer-lasting F0 raising throughout a large proportion of the preceding and following vowels. These effects appear to be imposed on a continuously changing F0 curve that is either rising-falling or falling-rising, depending on whether the carrier sentence is a statement or a question. Further analysis will test the hypothesis that these continuous curves result from local pitch targets that are assigned to individual syllables and implemented with them in synchrony regardless of their segmental composition. [Work supported by NIDCD Grant No. R01 DC03902.

  12. A Survey of Stellar Families: Multiplicity of Solar-Type Stars

    CERN Document Server

    Raghavan, Deepak; Henry, Todd J; Latham, David W; Marcy, Geoffrey W; Mason, Brian D; Gies, Douglas R; White, Russel J; Brummelaar, Theo A ten

    2010-01-01

    We present the results of a comprehensive assessment of companions to solar-type stars. A sample of 454 stars, including the Sun, was selected from the Hipparcos catalog with {\\pi} > 40 mas, {\\sigma}_{\\pi}/{\\pi} < 0.05, 0.5 < B - V < 1.0 (~ F6-K3), and constrained by absolute magnitude and color to exclude evolved stars. New observational aspects of this work include surveys for (1) very close companions with long-baseline interferometry at the CHARA Array, (2) close companions with speckle interferometry, and (3) wide proper motion companions identified by blinking multi-epoch archival images. In addition, we include the results from extensive radial-velocity monitoring programs and evaluate companion information from various catalogs. The overall observed fractions of single, double, triple, and higher order systems are 56% \\pm 2%, 33% \\pm 2%, 8% \\pm 1%, and 3% \\pm 1%, respectively, counting all confirmed stellar and brown dwarf companions. Our completeness analysis indicates that only a few undisc...

  13. Testing the Presence of Multiple Photometric Components in Nearby Early-type Galaxies using SDSS

    Science.gov (United States)

    Oh, Semyeong; Greene, Jenny E.; Lackner, Claire N.

    2017-02-01

    We investigate two-dimensional image decomposition of nearby, morphologically selected early-type galaxies (ETGs). We are motivated by recent observational evidence of significant size growth of quiescent galaxies and theoretical development advocating a two-phase formation scenario for ETGs. We find that a significant fraction of nearby ETGs show changes in isophotal shape that require multi-component models. The characteristic sizes of the inner and outer component are ∼3 and ∼15 kpc. The inner component lies on the mass–size relation of ETGs at z ∼ 0.25–0.75, while the outer component tends to be more elliptical and hints at a stochastic buildup process. We find real physical differences between single- and double-component ETGs, with double-component galaxies being younger and more metal-rich. The fraction of double-component ETGs increases with increasing σ and decreases in denser environments. We hypothesize that double-component systems were able to accrete gas and small galaxies until later times, boosting their central densities, building up their outer parts, and lowering their typical central ages. In contrast, the oldest galaxies, perhaps due to residing in richer environments, have no remaining hints of their last accretion episode.

  14. Leisure time activities of Iranian patients with multiple sclerosis: a qualitative study

    Directory of Open Access Journals (Sweden)

    Seyed Mohammad Sadegh Hosseini

    2016-03-01

    Conclusion: The results represented the range and heterogeneity of leisure activities amongst the MS patients. Considering participation in spiritual/religious and social activities as leisure time undertaking might reflect cultural diversity in the perception and use of time for recreation. For mental health promotion purposes, paying special attention to the types of activities that people of different socio-cultural background choose for their refreshment could help health care providers in giving tailored advice for patients with MS and other chronic debilitating disease.

  15. Interference activity of a minimal Type I CRISPR-Cas system from Shewanella putrefaciens.

    Science.gov (United States)

    Dwarakanath, Srivatsa; Brenzinger, Susanne; Gleditzsch, Daniel; Plagens, André; Klingl, Andreas; Thormann, Kai; Randau, Lennart

    2015-10-15

    Type I CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)-Cas (CRISPR-associated) systems exist in bacterial and archaeal organisms and provide immunity against foreign DNA. The Cas protein content of the DNA interference complexes (termed Cascade) varies between different CRISPR-Cas subtypes. A minimal variant of the Type I-F system was identified in proteobacterial species including Shewanella putrefaciens CN-32. This variant lacks a large subunit (Csy1), Csy2 and Csy3 and contains two unclassified cas genes. The genome of S. putrefaciens CN-32 contains only five Cas proteins (Cas1, Cas3, Cas6f, Cas1821 and Cas1822) and a single CRISPR array with 81 spacers. RNA-Seq analyses revealed the transcription of this array and the maturation of crRNAs (CRISPR RNAs). Interference assays based on plasmid conjugation demonstrated that this CRISPR-Cas system is active in vivo and that activity is dependent on the recognition of the dinucleotide GG PAM (Protospacer Adjacent Motif) sequence and crRNA abundance. The deletion of cas1821 and cas1822 reduced the cellular crRNA pool. Recombinant Cas1821 was shown to form helical filaments bound to RNA molecules, which suggests its role as the Cascade backbone protein. A Cascade complex was isolated which contained multiple Cas1821 copies, Cas1822, Cas6f and mature crRNAs.

  16. Seizure induces activation of multiple subtypes of neural progenitors and growth factors in hippocampus with neuronal maturation confined to dentate gyrus

    Energy Technology Data Exchange (ETDEWEB)

    Indulekha, Chandrasekharan L.; Sanalkumar, Rajendran [Neuro Stem Cell Biology Laboratory, Department of Neurobiology, Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, Kerala 695 014 (India); Thekkuveettil, Anoopkumar [Molecular Medicine, Biomedical Technology Wing, Sree Chitra Thirunal Institute for Medical Sciences and Technology, Thiruvananthapuram, Kerala (India); James, Jackson, E-mail: jjames@rgcb.res.in [Neuro Stem Cell Biology Laboratory, Department of Neurobiology, Rajiv Gandhi Center for Biotechnology, Thiruvananthapuram, Kerala 695 014 (India)

    2010-03-19

    Adult hippocampal neurogenesis is altered in response to different physiological and pathological stimuli. GFAP{sup +ve}/nestin{sup +ve} radial glial like Type-1 progenitors are considered to be the resident stem cell population in adult hippocampus. During neurogenesis these Type-1 progenitors matures to GFAP{sup -ve}/nestin{sup +ve} Type-2 progenitors and then to Type-3 neuroblasts and finally differentiates into granule cell neurons. In our study, using pilocarpine-induced seizure model, we showed that seizure initiated activation of multiple progenitors in the entire hippocampal area such as DG, CA1 and CA3. Seizure induction resulted in activation of two subtypes of Type-1 progenitors, Type-1a (GFAP{sup +ve}/nestin{sup +ve}/BrdU{sup +ve}) and Type-1b (GFAP{sup +ve}/nestin{sup +ve}/BrdU{sup -ve}). We showed that majority of Type-1b progenitors were undergoing only a transition from a state of dormancy to activated form immediately after seizures rather than proliferating, whereas Type-1a showed maximum proliferation by 3 days post-seizure induction. Type-2 (GFAP{sup -ve}/nestin{sup +ve}/BrdU{sup +ve}) progenitors were few compared to Type-1. Type-3 (DCX{sup +ve}) progenitors showed increased expression of immature neurons only in DG region by 3 days after seizure induction indicating maturation of progenitors happens only in microenvironment of DG even though progenitors are activated in CA1 and CA3 regions of hippocampus. Also parallel increase in growth factors expression after seizure induction suggests that microenvironmental niche has a profound effect on stimulation of adult neural progenitors.

  17. Multiple patterns of writing disorders in dementia of the Alzheimer type and their evolution.

    Science.gov (United States)

    Luzzatti, Claudio; Laiacona, Marcella; Agazzi, Daniela

    2003-01-01

    This paper reports the results obtained from a writing task given to 23 Italian patients suffering from mild to moderate dementia of the Alzheimer's type (DAT). Spelling performance was tested with a task that taps the sub-word-level (spelling of regular words and nonwords), and the lexical route (spelling of regular and irregular words), in line with contemporary models of writing. Each patient's performance was classified according to the emergence of dissociated patterns of damage between regular words and nonwords and between regular and irregular words. The 23 DAT patients span the whole spectrum of dysgraphic taxonomy; five showed the characteristic pattern of impairment of surface dysgraphia, two showed the characteristics of phonological dysgraphia, while a mixed pattern (i.e. better performance on regular words compared to irregular words and regular nonwords) emerged in seven cases. Three patients presented undifferentiated writing disorders, two were completely agraphic, while four patients showed only minimal or no writing defects. The rate of dissociated impairments in the lexical and the sub-word-level routine is very similar to that observed after acute focal brain damage, which contradicts the hypothesis that degenerative brain damage selectively impairs writing performance along the lexical-semantic route. To test the hypothesis that surface sub-word-level processing abilities are affected only during the evolution of the disease, nine patients were tested longitudinally after an interval of 6-12 months. Once again, the data showed high variability across subjects, and do not seem to support involvement of the sub-word-level spelling routine only at a late stage in the development of the disease.

  18. Evaluation of multiple-frequency, active and passive acoustics as surrogates for bedload transport

    Science.gov (United States)

    Wood, Molly S.; Fosness, Ryan L.; Pachman, Gregory; Lorang, Mark; Tonolla, Diego

    2015-01-01

    The use of multiple-frequency, active acoustics through deployment of acoustic Doppler current profilers (ADCPs) shows potential for estimating bedload in selected grain size categories. The U.S. Geological Survey (USGS), in cooperation with the University of Montana (UM), evaluated the use of multiple-frequency, active and passive acoustics as surrogates for bedload transport during a pilot study on the Kootenai River, Idaho, May 17-18, 2012. Four ADCPs with frequencies ranging from 600 to 2000 kHz were used to measure apparent moving bed velocities at 20 stations across the river in conjunction with physical bedload samples. Additionally, UM scientists measured the sound frequencies of moving particles with two hydrophones, considered passive acoustics, along longitudinal transects in the study reach. Some patterns emerged in the preliminary analysis which show promise for future studies. Statistically significant relations were successfully developed between apparent moving bed velocities measured by ADCPs with frequencies 1000 and 1200 kHz and bedload in 0.5 to 2.0 mm grain size categories. The 600 kHz ADCP seemed somewhat sensitive to the movement of gravel bedload in the size range 8.0 to 31.5 mm, but the relation was not statistically significant. The passive hydrophone surveys corroborated the sample results and could be used to map spatial variability in bedload transport and to select a measurement cross-section with moving bedload for active acoustic surveys and physical samples.

  19. Intractable and highly active relapsing multiple sclerosis – role of alemtuzumab

    Directory of Open Access Journals (Sweden)

    Dubey D

    2015-09-01

    Full Text Available Divyanshu Dubey,1 Christopher A Cano,1 Olaf Stuve1–3 1Department of Neurology and Neurotherapeutics, University of Texas Southwestern Medical Center, 2Neurology Section, VA North Texas Health Care System, Medical Service, Dallas, TX, USA; 3Department of Neurology, Klinikum rechts der Isar, Technische Universität München, Munich, Germany Abstract: Alemtuzumab is a humanized recombinant monoclonal antibody that was recently approved by the US Food and Drug Administration and the European Medicines Agency for the management of relapsing forms of multiple sclerosis (MS. It has been utilized for the management of chronic lymphocytic leukemia, bone marrow and renal transplantation, or graft versus host disease. Because of its immunomodulatory properties, it was brought into clinical development in MS. One Phase II (CAMMS223 and two Phase III clinical trials (CARE-MSI and -II have evaluated the safety and efficacy of alemtuzumab in patients with relapsing–remitting MS. Even though its efficacy profile and long-lasting effect have attracted much interest among physicians and patients, it has significant potential adverse effects that may limit its use to patients with active disease. Here, we review the history of drug development of alemtuzumab. Furthermore, we outline the postulated mechanisms of action, clinical evidence, and safety of alemtuzumab for its use as a disease-modifying agent in active and highly active MS. Keywords: alemtuzumab, multiple sclerosis, monoclonal antibody, CD52, idiopathic thrombocytopenic purpura

  20. Multiple Legionella pneumophila Type II secretion substrates, including a novel protein, contribute to differential infection of the amoebae Acanthamoeba castellanii, Hartmannella vermiformis, and Naegleria lovaniensis.

    Science.gov (United States)

    Tyson, Jessica Y; Pearce, Meghan M; Vargas, Paloma; Bagchi, Sreya; Mulhern, Brendan J; Cianciotto, Nicholas P

    2013-05-01

    Type II protein secretion (T2S) by Legionella pneumophila is required for intracellular infection of host cells, including macrophages and the amoebae Acanthamoeba castellanii and Hartmannella vermiformis. Previous proteomic analysis revealed that T2S by L. pneumophila 130b mediates the export of >25 proteins, including several that appeared to be novel. Following confirmation that they are unlike known proteins, T2S substrates NttA, NttB, and LegP were targeted for mutation. nttA mutants were impaired for intracellular multiplication in A. castellanii but not H. vermiformis or macrophages, suggesting that novel exoproteins which are specific to Legionella are especially important for infection. Because the importance of NttA was host cell dependent, we examined a panel of T2S substrate mutants that had not been tested before in more than one amoeba. As a result, RNase SrnA, acyltransferase PlaC, and metalloprotease ProA all proved to be required for optimal intracellular multiplication in H. vermiformis but not A. castellanii. Further examination of an lspF mutant lacking the T2S apparatus documented that T2S is also critical for infection of the amoeba Naegleria lovaniensis. Mutants lacking SrnA, PlaC, or ProA, but not those deficient for NttA, were defective in N. lovaniensis. Based upon analysis of a double mutant lacking PlaC and ProA, the role of ProA in H. vermiformis was connected to its ability to activate PlaC, whereas in N. lovaniensis, ProA appeared to have multiple functions. Together, these data document that the T2S system exports multiple effectors, including a novel one, which contribute in different ways to the broad host range of L. pneumophila.

  1. Surface modification of Cobalt ferrite nano-hollowspheres for inherent multiple photoluminescence and enhanced photocatalytic activities

    Science.gov (United States)

    Talukdar, Souvanik; Mandal, Dipika; Mandal, Kalyan

    2017-03-01

    Nano-hollow spheres (NHSs) are the new drift in magnetic nanostructures as they provide more surface area at nano length scale with enhanced magnetic properties compared to their nanoparticle counterpart. Here we reported the synthesis of biocompatible CoFe2O4 NHSs of diameter around 250 nm and emergence of intrinsic multiple photoluminescence from blue, green to red on modifying their surface with small organic ligands like tartrate. The surface modified NHSs also showed notable photocatalytic activity towards the degradation of environmentally malefic dyes like Methylene Blue and Rhodamine B. The surface modified NHSs are found to exhibit superior magnetic properties.

  2. Biological Activity of Lenalidomide and Its Underlying Therapeutic Effects in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Roberta Martiniani

    2012-01-01

    Full Text Available Lenalidomide is a synthetic compound derived by modifying the chemical structure of thalidomide. It belongs to the second generation of immunomodulatory drugs (IMiDs and possesses pleiotropic properties. Even if lenalidomide has been shown to be active in the treatment of several hematologic malignancies, this review article is mostly focalized on its mode of action in multiple myeloma. The present paper is about the direct and indirect antitumor effects of lenalidomide on malignant plasmacells, bone marrow microenvironment, bone resorption and host’s immune response. The molecular mechanisms and targets of lenalidomide remain largely unknown, but recent evidence shows cereblon (CRBN as a possible mediator of its therapeutical effects.

  3. Subcutaneous administration of alemtuzumab in patients with highly active multiple sclerosis.

    Science.gov (United States)

    Perumal, Jai S; Foo, Farng; Cook, Perry; Khan, Omar

    2012-08-01

    Alemtuzumab is an anti-CD52 monoclonal antibody with remarkable efficacy in relapsing multiple sclerosis (MS). In clinical trials and off-label use in MS, alemtuzumab has been administered intravenously (IV). Alemtuzumab is approved for chronic lymphoid leukemia as IV. Oncology guidelines recommend alemtuzumab subcutaneous (SC) over IV. There is no report of alemtuzumab SC in MS. We report two patients with highly active relapsing MS who were treated with SC alemtuzumab, had significant improvement and tolerated SC alemtuzumab well without the typical infusion-associated adverse events. SC alemtuzumab in MS warrants further studies as this may enhance patient convenience and minimize infusion-associated adverse events.

  4. Impact of childhood exposure to psychological trauma on the risk of psychiatric disorders and somatic discomfort: single vs. multiple types of psychological trauma.

    Science.gov (United States)

    Park, Subin; Hong, Jin Pyo; Bae, Jae Nam; Cho, Seong-Jin; Lee, Dong-Woo; Lee, Jun-Young; Chang, Sung Man; Jeon, Hong Jin; Hahm, Bong-Jin; Lee, Young Moon; Seong, Sujeong; Cho, Maeng Je

    2014-11-30

    We examined whether childhood exposure to multiple types of potentially traumatic events (PTEs) relative to a single type of PTE is associated with a higher prevalence of psychiatric disorders and greater somatic discomfort in Korean adults. The Composite International Diagnostic Interview 2.1 (K-CIDI 2.1) was administered to 6027 subjects aged 18-74 years. Subjects who experienced a traumatic event before the age of 18 years, the childhood trauma exposure group, were compared with controls without childhood exposure to PTEs. In the childhood trauma exposure group, subjects who experienced only a single type of PTE and subjects who experienced two or more types of PTEs were compared further. Childhood exposure to PTEs was linked to a wide range of psychiatric comorbidities, with a higher risk for exposure to multiple types of PTEs than for exposure to a single type of PTE. Obsessive-compulsive disorder, generalized anxiety disorder, and somatoform disorder were significantly associated with exposure to multiple types of PTEs but not with exposure to a single type of PTE. Exposure to multiple types of PTEs was associated with reports of marked fatigue and pain. Future research should examine the psychiatric sequelae associated with various types of childhood PTEs.

  5. Evidence of impaired brain activity balance after passive sensorimotor stimulation in multiple sclerosis.

    Directory of Open Access Journals (Sweden)

    Nikolaos Petsas

    Full Text Available OBJECTIVES: Examination of sensorimotor activation alone in multiple sclerosis (MS patients may not yield a comprehensive view of cerebral response to task stimulation. Additional information may be obtained by examining the negative BOLD response (deactivation. Aim of this work was to characterize activation and deactivation patterns during passive hand movements in MS patients. METHODS: 13 relapsing remitting-MS patients (RRMS, 18 secondary progressive-MS patients (SPMS and 15 healthy controls (HC underwent an fMRI study during passive right-hand movements. Activation and deactivation contrasts in the three groups were entered into ANOVA, age and gender corrected. Post-hoc analysis was performed with one-sample and two-sample t-tests. For each patient we obtained lesion volume (LV from both T1- and T2-weighted images. RESULTS: Activations showed a progressive extension to the ipsilateral brain hemisphere according to the group and the clinical form (HCactivation in the contralateral sensorimotor cortex was significantly correlated with that of deactivation in the DMN in HC and RRMS, but not in SPMS. Both increased activation and decreased deactivation patterns correlated with LV. CONCLUSION: In RRMS patients, increased cortical activation was associated with increased deactivation of the posterior cortex suggesting a greater resting-state activity in the DMN, probably aimed at facilitating sensorimotor circuit engagement during task performance. In SPMS the coupling between increased sensorimotor activation/increased DMN deactivation was not observed suggesting disorganization between anticorrelated functional networks as a consequence of a higher

  6. Cucurbitacin IIb exhibits anti-inflammatory activity through modulating multiple cellular behaviors of mouse lymphocytes.

    Directory of Open Access Journals (Sweden)

    Yao Wang

    Full Text Available Cucurbitacin IIb (CuIIb is one of the major active compounds in Hemsleyadine tablets which have been used for clinical treatment of bacillary dysentery, enteritis and acute tonsilitis. However, its action mechanism has not been completely understood. This study aimed to explore the anti-inflammatory activity of CuIIb and its underlying mechanism in mitogen-activated lymphocytes isolated from mouse mesenteric lymph nodes. The results showed that CuIIb inhibited the proliferation of concanavalin A (Con A-activated lymphocytes in a time- and dose-dependent manner. CuIIb treatment arrested their cell cycle in S and G2/M phases probably due to the disruption of the actin cytoskeleton and the modulation of p27(Kip1 and cyclin levels. Moreover, the surface expression of activation markers CD69 and CD25 on Con A-activated CD3(+ T lymphocytes was suppressed by CuIIb treatment. Both Con A- and phorbol ester plus ionomycin-induced expression of TNF-α, IFN-γ and IL-6 proteins was attenuated upon exposure to CuIIb. Mechanistically, CuIIb treatment suppressed the phosphorylation of JNK and Erk1/2 but not p38 in Con A-activated lymphocytes. Although CuIIb unexpectedly enhanced the phosphorylation of IκB and NF-κB (p65, it blocked the nuclear translocation of NF-κB (p65. In support of this, CuIIb significantly decreased the mRNA levels of IκBα and TNF-α, two target genes of NF-κB, in Con A-activated lymphocytes. In addition, CuIIb downregulated Con A-induced STAT3 phosphorylation and increased cell apoptosis. Collectively, these results suggest that CuIIb exhibits its anti-inflammatory activity through modulating multiple cellular behaviors and signaling pathways, leading to the suppression of the adaptive immune response.

  7. Identification of a common Wnt-associated genetic signature across multiple cell types in pulmonary arterial hypertension.

    Science.gov (United States)

    West, James D; Austin, Eric D; Gaskill, Christa; Marriott, Shennea; Baskir, Rubin; Bilousova, Ganna; Jean, Jyh-Chang; Hemnes, Anna R; Menon, Swapna; Bloodworth, Nathaniel C; Fessel, Joshua P; Kropski, Johnathan A; Irwin, David; Ware, Lorraine B; Wheeler, Lisa; Hong, Charles C; Meyrick, Barbara; Loyd, James E; Bowman, Aaron B; Ess, Kevin C; Klemm, Dwight J; Young, Pampee P; Merryman, W David; Kotton, Darrell; Majka, Susan M

    2014-09-01

    Understanding differences in gene expression that increase risk for pulmonary arterial hypertension (PAH) is essential to understanding the molecular basis for disease. Previous studies on patient samples were limited by end-stage disease effects or by use of nonadherent cells, which are not ideal to model vascular cells in vivo. These studies addressed the hypothesis that pathological processes associated with PAH may be identified via a genetic signature common across multiple cell types. Expression array experiments were initially conducted to analyze cell types at different stages of vascular differentiation (mesenchymal stromal and endothelial) derived from PAH patient-specific induced pluripotent stem (iPS) cells. Molecular pathways that were altered in the PAH cell lines were then compared with those in fibroblasts from 21 patients, including those with idiopathic and heritable PAH. Wnt was identified as a target pathway and was validated in vitro using primary patient mesenchymal and endothelial cells. Taken together, our data suggest that the molecular lesions that cause PAH are present in all cell types evaluated, regardless of origin, and that stimulation of the Wnt signaling pathway was a common molecular defect in both heritable and idiopathic PAH.

  8. Secreted phospholipase A2 activity in experimental autoimmune encephalomyelitis and multiple sclerosis

    Directory of Open Access Journals (Sweden)

    Blankenhorn Elizabeth P

    2006-09-01

    Full Text Available Abstract Background There is increased interest in the contribution of the innate immune system to multiple sclerosis (MS, including the activity of acute inflammatory mediators. The purpose of this study was to test the involvement of systemic secreted phospholipase A2 (sPLA2 enzymes in experimental autoimmune encephalomyelitis (EAE, an MS model, and to determine if enzyme activity is elevated in MS patients. Methods A non-invasive urinary assay was developed in order to monitor enzymatically active sPLA2 levels in Dark Agouti rats after induction of EAE. Some Rats were treated with nonapeptide CHEC-9, an uncompetitive sPLA2 enzyme inhibitor, during the initial rise in urinary enzyme levels. Body weight and clinical EAE score were measured for 18 days post immunization (PI, after which the rats were sacrificed for H&E and myelin staining, and for ED-1 immunocytochemistry, the latter to quantify macrophages and activated microglia. The urinary sPLA2 assay was also applied to un-timed samples collected from a cross section of 44 MS patients and 14 healthy controls. Results Mean levels of enzymatically active sPLA2 in the urine increased following immunization and peaked between days 8–10 PI which was just prior to the onset of EAE symptoms. At this time, a transient attenuation of activity was detected in the urine of CHEC-9 treated rats consistent with the activity-dependent properties of the inhibitor. The peptide also reduced or abolished EAE symptoms compared to vehicle-injected controls. Histopathological changes in the spinal cords of the EAE rats correlated generally with clinical score including a significant reduction in ED-1+ cells after peptide treatment. Multiple Sclerosis patients also showed elevations in sPLA2 enzyme activity. Mean levels of sPLA2 were increased 6-fold in the urine of patients with active disease and 4-fold for patients in remission, regardless of immunomodulating therapy. Conclusion The results suggest that s

  9. Regulatory Cell Populations in Relapsing-Remitting Multiple Sclerosis (RRMS) Patients: Effect of Disease Activity and Treatment Regimens

    Science.gov (United States)

    Rodi, Maria; Dimisianos, Nikolaos; de Lastic, Anne-Lise; Sakellaraki, Panagiota; Deraos, George; Matsoukas, John; Papathanasopoulos, Panagiotis; Mouzaki, Athanasia

    2016-01-01

    Multiple sclerosis (MS) is a demyelinating disease of the central nervous system (CNS) of autoimmune etiology that results from an imbalance between CNS-specific T effector cells and peripheral suppressive mechanisms mediated by regulatory cells (RC). In this research, we collected blood samples from 83 relapsing remitting MS (RRMS) patients and 45 healthy persons (HC), to assess the sizes of their RC populations, including CD4+CD25highFoxp3+ (nTregs), CD3+CD4+HLA−G+, CD3+CD8+CD28−, CD3+CD56+, and CD56bright cells, and how RC are affected by disease activity (acute phase or remission) and types of treatment (methylprednisolone, interferon, or natalizumab). In addition, we isolated peripheral blood mononuclear cells (PBMC) and cultured them with peptides mapping to myelin antigens, to determine RC responsiveness to autoantigens. The results showed decreased levels of nTregs in patients in the acute phase ± methylprednisolone and in remission + natalizumab, but HC levels in patients in remission or receiving interferon. Patients + interferon had the highest levels of CD3+CD4+HLA−G+ and CD3+CD8+CD28− RC, and patients in the acute phase + methylprednisolone the lowest. Patients in remission had the highest levels of CD3+CD56+, and patients in remission + natalizumab the highest levels of CD56bright cells. Only nTregs responded to autoantigens in culture, regardless of disease activity or treatment. The highest suppressive activity was exhibited by nTregs from patients in remission. In conclusion, in RRMS disease activity and type of treatment affect different RC populations. nTregs respond to myelin antigens, indicating that it is possible to restore immunological tolerance through nTreg induction. PMID:27571060

  10. A new type of NtrC transcriptional activator.

    OpenAIRE

    Foster-Hartnett, D; Cullen, P. J.; Monika, E M; Kranz, R G

    1994-01-01

    The enteric NtrC (NRI) protein has been the paradigm for a class of bacterial enhancer-binding proteins (EBPs) that activate transcription of RNA polymerase containing the sigma 54 factor. Activators in the NtrC class are characterized by essentially three properties: (i) they bind to sites distant from the promoters that they activate (> 100 bp upstream of the transcriptional start site), (ii) they contain a conserved nucleotide-binding fold and exhibit ATPase activity that is required for a...

  11. Prevention of Paclitaxel-Induced Neuropathy Through Activation of the Central Cannabinoid Type 2 Receptor System

    Science.gov (United States)

    Naguib, Mohamed; Xu, Jijun J.; Diaz, Philippe; Brown, David L.; Cogdell, David; Bie, Bihua; Hu, Jianhua; Craig, Suzanne; Hittelman, Walter N.

    2012-01-01

    Background Peripheral neuropathy is a major dose-limiting toxicity of chemotherapy, especially after multiple courses of paclitaxel. The development of paclitaxel-induced neuropathy is associated with the activation of microglia followed by the activation and proliferation of astrocytes, and the expression and release of proinflammatory cytokines in the spinal dorsal horn. Cannabinoid type 2 (CB2) receptors are expressed in the microglia in neurodegenerative disease models. Methods To explore the potential of CB2 agonists for preventing paclitaxel-induced neuropathy, we designed and synthesized a novel CB2-selective agonist, namely MDA7. The effect of MDA7 in preventing paclitaxel-induced allodynia was assessed in rats and in CB2+/+ and CB2–/– mice. We hypothesize that the CB2 receptor functions in a negative-feedback loop and that early MDA7 administration can blunt the neuroinflammatory response to paclitaxel and prevent mechanical allodynia through interference with specific signaling pathways. Results We found that MDA7 prevents paclitaxel-induced mechanical allodynia in rats and mice in a dose- and time-dependent manner without compromising paclitaxel's antineoplastic effect. MDA7's neuroprotective effect was absent in CB2-/- mice and was blocked by CB2 antagonists, suggesting that MDA7's action directly involves CB2 receptor activation. MDA7 treatment was found to interfere with early events in the paclitaxel-induced neuroinflammatory response as evidenced by relatively reduced Toll-like receptor and CB2 expression in the lumbar spinal cord, reduced levels of extracellular signal regulated kinase 1/2 activity, reduced numbers of activated microglia and astrocytes, and reduced secretion of proinflammatory mediators in vivo and in in vitro models. Conclusions Our findings suggest an innovative therapeutic approach to prevent chemotherapy-induced neuropathy and may permit more aggressive use of active chemotherapeutic regimens with reduced long-term sequelae

  12. Multiple attractors in the response of a flexible rotor in active magnetic bearings with geometric coupling

    Energy Technology Data Exchange (ETDEWEB)

    Inayat-Hussain, J I [School of Engineering, Monash University, Jalan Lagoon Selatan, 46150 Bandar Sunway, Selangor Darul Ehsan (Malaysia)], E-mail: jawaid.inayat-hussain@eng.monash.edu.my

    2008-02-15

    Numerical results on the response of a flexible rotor supported by nonlinear active magnetic bearings are presented. Nonlinearity arising from the magnetic actuator forces that are nonlinear functions of the coil current and the air gap between the rotor and the stator, and from the geometric coupling of the magnetic actuators is incorporated into the mathematical model of the flexible rotor - active magnetic bearing system. For relatively large values of the geometric coupling parameter, the response of the rotor with the variation of the speed parameter within the range 0.05 {<=}{omega} {<=} 5.0 displayed a rich variety of nonlinear dynamical phenomena including sub-synchronous vibrations of periods -2, -3, -6, -9, and -17, quasi-periodicity and chaos. Numerical results also reveal the occurrence of bi-stable operation within certain ranges of the speed parameter where multiple attractors may co-exist at the same speed parameter value depending on the operating speed of the rotor.

  13. Evaluation of the multiple-stimulus without replacement preference assessment method using activities as stimuli.

    Science.gov (United States)

    Daly, Edward J; Wells, Nikki J; Swanger-Gagné, Michelle S; Carr, James E; Kunz, Gina M; Taylor, Ashley M

    2009-01-01

    The current study examined the accuracy of the multiple-stimulus without replacement (MSWO) preference assessment for identifying preferred common classroom activities as reinforcers with children with behavioral disorders. The accuracy of predictions from the MSWO regarding high, medium, and low stimulus preference was tested by providing contingent access to activities for completing math problems within an independent seatwork format. Overall, there was an interaction effect between preference ranking (high, medium, or low) and number of problems completed. The results confirm and extend previous findings regarding the accuracy of predictions with the MSWO. The findings also reveal, however, some individual differences that may account for instances in which student behavior did not conform to predictions of stimulus preference assessments.

  14. Dynamic synchronization and chaos in an associative neural network with multiple active memories.

    Science.gov (United States)

    Raffone, Antonino; van Leeuwen, Cees

    2003-09-01

    Associative memory dynamics in neural networks are generally based on attractors. Retrieval based on fixed-point attractors works if only one memory pattern is retrieved at the time, but cannot enable the simultaneous retrieval of more than one pattern. Stable phase-locking of periodic oscillations or limit cycle attractors leads to incorrect feature bindings if the simultaneously retrieved patterns share some of their features. We investigate retrieval dynamics of multiple active patterns in a network of chaotic model neurons. Several memory patterns are kept simultaneously active and separated from each other by a dynamic itinerant synchronization between neurons. Neurons representing shared features alternate their synchronization between patterns, thus multiplexing their binding relationships. Our model includes a mechanism for self-organized readout or decoding of memory pattern coherence in terms of short-term potentiation and short-term depression of synaptic weights.

  15. Rapid development of thymic neuroendocrine carcinoma despite transcervical thymectomy in a patient with multiple endocrine neoplasia type 1

    Directory of Open Access Journals (Sweden)

    Dhalapathy Sadacharan

    2013-01-01

    Full Text Available Thymic neuroendocrine (NE tumors are a rare manifestation of multiple endocrine neoplasia syndrome type 1 (MEN-1. They are malignant and aggressive tumors and form a major cause of mortality in MEN-1. Transcervical thymectomy (TCT at the time of parathyroid surgery for primary hyperparathyroidism (PHPT in MEN-1 usually prevents thymic NE tumors. We report a 56-year-old nonsmoker male with sporadic MEN-1 who presented with thymic NE carcinoma developing rapidly within a span of 8 months after subtotal parathyroidectomy and TCT for PHPT. We present a brief review of literature on this rare NE malignancy, focusing on its occurrence despite TCT. This case highlights the fact that thymic NE carcinoma may develop even after TCT in MEN-1. Regular surveillance for these aggressive thymic NE tumors is mandatory even after TCT in MEN-1 setting.

  16. Persistent activation of microglia and NADPH oxidase [corrected] drive hippocampal dysfunction in experimental multiple sclerosis.

    Science.gov (United States)

    Di Filippo, Massimiliano; de Iure, Antonio; Giampà, Carmela; Chiasserini, Davide; Tozzi, Alessandro; Orvietani, Pier Luigi; Ghiglieri, Veronica; Tantucci, Michela; Durante, Valentina; Quiroga-Varela, Ana; Mancini, Andrea; Costa, Cinzia; Sarchielli, Paola; Fusco, Francesca Romana; Calabresi, Paolo

    2016-02-18

    Cognitive impairment is common in multiple sclerosis (MS). Unfortunately, the synaptic and molecular mechanisms underlying MS-associated cognitive dysfunction are largely unknown. We explored the presence and the underlying mechanism of cognitive and synaptic hippocampal dysfunction during the remission phase of experimental MS. Experiments were performed in a chronic-relapsing experimental autoimmune encephalomyelitis (EAE) model of MS, after the resolution of motor deficits. Immunohistochemistry and patch-clamp recordings were performed in the CA1 hippocampal area. The hole-board was utilized as cognitive/behavioural test. In the remission phase of experimental MS, hippocampal microglial cells showed signs of activation, CA1 hippocampal synapses presented an impaired long-term potentiation (LTP) and an alteration of spatial tests became evident. The activation of hippocampal microglia mediated synaptic and cognitive/behavioural alterations during EAE. Specifically, LTP blockade was found to be caused by the reactive oxygen species (ROS)-producing enzyme nicotinamide adenine dinucleotide phosphate (NADPH) oxidase. We suggest that in the remission phase of experimental MS microglia remains activated, causing synaptic dysfunctions mediated by NADPH oxidase. Inhibition of microglial activation and NADPH oxidase may represent a promising strategy to prevent neuroplasticity impairment associated with active neuro-inflammation, with the aim to improve cognition and counteract MS disease progression.

  17. Multiple low-grade sarcomas of fibroblastic type in the setting of HIV and acquired epidermodysplasia verruciformis.

    Science.gov (United States)

    Dosal, Jacquelyn; Nelson, Ann M; Shelling, Michael; Romaguera, Rita; Poulos, Evangelos; Alonso-Llamazares, Javier

    2014-10-01

    A 46-year-old white male with a history of HIV (CD4 245), acquired epidermodysplasia verruciformis, anal carcinoma in situ, hepatitis B and C presented with 3 asymptomatic, nontender, firm pink/skin-colored nodules involving the arm, left lateral leg, and right third finger. One year later, he developed a similar lesion on his right medial lower leg. Excisional biopsy of one of the lesions showed an atypical spindle cell neoplasm of the dermis compatible with a low-grade sarcoma of fibroblastic origin. Testing for human herpes virus-8, 23 human papillomavirus types, Epstein-Barr virus, and FUS fusion protein were negative. The patient underwent diagnostic imaging with computed tomography scans of the chest, abdomen, and pelvis along with positron emission tomography scan to ensure that there was no other occult primary tumor, all of which were negative. The lesions were excised and have not recurred with 3 years of follow-up. The best histopathologic term for these lesions is multiple low-grade sarcomas of fibroblastic phenotype. They have been proven to be nonaggressive, with little or no metastatic potential. This is a neoplastic process that has not been well defined in the literature. To our knowledge, there are no previous reports of these lesions occurring in multiple sites or in an HIV-positive patient.

  18. Microsatellite typing of clinical and environmental Cryptococcus neoformans var. grubii isolates from Cuba shows multiple genetic lineages.

    Directory of Open Access Journals (Sweden)

    Maria-Teresa Illnait-Zaragozi

    Full Text Available BACKGROUND: Human cryptococcal infections have been associated with bird droppings as a likely source of infection. Studies toward the local and global epidemiology of Cryptococcus spp. have been hampered by the lack of rapid, discriminatory, and exchangeable molecular typing methods. METHODOLOGY/PRINCIPAL FINDINGS: We selected nine microsatellite markers for high-resolution fingerprinting from the genome of C. neoformans var. grubii. This panel of markers was applied to a collection of clinical (n = 122 and environmental (n = 68; from pigeon guano C. neoformans var. grubii isolates from Cuba. All markers proved to be polymorphic. The average number of alleles per marker was 9 (range 5-51. A total of 104 genotypes could be distinguished. The discriminatory power of this panel of markers was 0.993. Multiple clusters of related genotypes could be discriminated that differed in only one or two microsatellite markers. These clusters were assigned as microsatellite complexes. The majority of environmental isolates (>70% fell into 1 microsatellite complex containing only few clinical isolates (49 environmental versus 2 clinical. Clinical isolates were segregated over multiple microsatellite complexes. CONCLUSIONS/SIGNIFICANCE: A large genotypic variation exists in C. neoformans var. grubii. The genotypic segregation between clinical and environmental isolates from pigeon guano suggests additional source(s of human cryptococcal infections. The selected panel of microsatellite markers is an excellent tool to study the epidemiology of C. neoformans var. grubii.

  19. Identifying candidate genes for Type 2 Diabetes Mellitus and obesity through gene expression profiling in multiple tissues or cells.

    Science.gov (United States)

    Chen, Junhui; Meng, Yuhuan; Zhou, Jinghui; Zhuo, Min; Ling, Fei; Zhang, Yu; Du, Hongli; Wang, Xiaoning

    2013-01-01

    Type 2 Diabetes Mellitus (T2DM) and obesity have become increasingly prevalent in recent years. Recent studies have focused on identifying causal variations or candidate genes for obesity and T2DM via analysis of expression quantitative trait loci (eQTL) within a single tissue. T2DM and obesity are affected by comprehensive sets of genes in multiple tissues. In the current study, gene expression levels in multiple human tissues from GEO datasets were analyzed, and 21 candidate genes displaying high percentages of differential expression were filtered out. Specifically, DENND1B, LYN, MRPL30, POC1B, PRKCB, RP4-655J12.3, HIBADH, and TMBIM4 were identified from the T2DM-control study, and BCAT1, BMP2K, CSRNP2, MYNN, NCKAP5L, SAP30BP, SLC35B4, SP1, BAP1, GRB14, HSP90AB1, ITGA5, and TOMM5 were identified from the obesity-control study. The majority of these genes are known to be involved in T2DM and obesity. Therefore, analysis of gene expression in various tissues using GEO datasets may be an effective and feasible method to determine novel or causal genes associated with T2DM and obesity.

  20. Identifying Candidate Genes for Type 2 Diabetes Mellitus and Obesity through Gene Expression Profiling in Multiple Tissues or Cells

    Science.gov (United States)

    Meng, Yuhuan; Zhou, Jinghui; Zhuo, Min; Ling, Fei; Zhang, Yu; Du, Hongli; Wang, Xiaoning

    2013-01-01

    Type 2 Diabetes Mellitus (T2DM) and obesity have become increasingly prevalent in recent years. Recent studies have focused on identifying causal variations or candidate genes for obesity and T2DM via analysis of expression quantitative trait loci (eQTL) within a single tissue. T2DM and obesity are affected by comprehensive sets of genes in multiple tissues. In the current study, gene expression levels in multiple human tissues from GEO datasets were analyzed, and 21 candidate genes displaying high percentages of differential expression were filtered out. Specifically, DENND1B, LYN, MRPL30, POC1B, PRKCB, RP4-655J12.3, HIBADH, and TMBIM4 were identified from the T2DM-control study, and BCAT1, BMP2K, CSRNP2, MYNN, NCKAP5L, SAP30BP, SLC35B4, SP1, BAP1, GRB14, HSP90AB1, ITGA5, and TOMM5 were identified from the obesity-control study. The majority of these genes are known to be involved in T2DM and obesity. Therefore, analysis of gene expression in various tissues using GEO datasets may be an effective and feasible method to determine novel or causal genes associated with T2DM and obesity. PMID:24455749

  1. Identifying Candidate Genes for Type 2 Diabetes Mellitus and Obesity through Gene Expression Profiling in Multiple Tissues or Cells

    Directory of Open Access Journals (Sweden)

    Junhui Chen

    2013-01-01

    Full Text Available Type 2 Diabetes Mellitus (T2DM and obesity have become increasingly prevalent in recent years. Recent studies have focused on identifying causal variations or candidate genes for obesity and T2DM via analysis of expression quantitative trait loci (eQTL within a single tissue. T2DM and obesity are affected by comprehensive sets of genes in multiple tissues. In the current study, gene expression levels in multiple human tissues from GEO datasets were analyzed, and 21 candidate genes displaying high percentages of differential expression were filtered out. Specifically, DENND1B, LYN, MRPL30, POC1B, PRKCB, RP4-655J12.3, HIBADH, and TMBIM4 were identified from the T2DM-control study, and BCAT1, BMP2K, CSRNP2, MYNN, NCKAP5L, SAP30BP, SLC35B4, SP1, BAP1, GRB14, HSP90AB1, ITGA5, and TOMM5 were identified from the obesity-control study. The majority of these genes are known to be involved in T2DM and obesity. Therefore, analysis of gene expression in various tissues using GEO datasets may be an effective and feasible method to determine novel or causal genes associated with T2DM and obesity.

  2. Ultrasonic waste activated sludge disintegration for recovering multiple nutrients for biofuel production.

    Science.gov (United States)

    Xie, Guo-Jun; Liu, Bing-Feng; Wang, Qilin; Ding, Jie; Ren, Nan-Qi

    2016-04-15

    Waste activated sludge is a valuable resource containing multiple nutrients, but is currently treated and disposed of as an important source of pollution. In this work, waste activated sludge after ultrasound pretreatment was reused as multiple nutrients for biofuel production. The nutrients trapped in sludge floc were transferred into liquid medium by ultrasonic disintegration during first 30 min, while further increase of pretreatment time only resulted in slight increase of nutrients release. Hydrogen production by Ethanoligenens harbinense B49 from glucose significantly increased with the concentration of ultrasonic sludge, and reached maximum yield of 1.97 mol H2/mol glucose at sludge concentration of 7.75 g volatile suspended solids/l. Without addition of any other chemicals, waste molasses rich in carbohydrate was efficiently turned into hydrogen with yield of 189.34 ml H2/g total sugar by E. harbinense B49 using ultrasonic sludge as nutrients. The results also showed that hydrogen production using pretreated sludge as multiple nutrients was higher than those using standard nutrients. Acetic acid produced by E. harbinense B49 together with the residual nutrients in the liquid medium were further converted into hydrogen (271.36 ml H2/g total sugar) by Rhodopseudomonas faecalis RLD-53 through photo fermentation, while ethanol was the sole end product with yield of 220.26 mg/g total sugar. Thus, pretreated sludge was an efficient nutrients source for biofuel production, which could replace the standard nutrients. This research provided a novel strategy to achieve environmental friendly sludge disposal and simultaneous efficient biofuel recovery from organic waste.

  3. The bone marrow microenvironment enhances multiple myeloma progression by exosome-mediated activation of myeloid-derived suppressor cells.

    Science.gov (United States)

    Wang, Jinheng; De Veirman, Kim; De Beule, Nathan; Maes, Ken; De Bruyne, Elke; Van Valckenborgh, Els; Vanderkerken, Karin; Menu, Eline

    2015-12-22

    Exosomes, extracellular nanovesicles secreted by various cell types, modulate the bone marrow (BM) microenvironment by regulating angiogenesis, cytokine release, immune response, inflammation, and metastasis. Interactions between bone marrow stromal cells (BMSCs) and multiple myeloma (MM) cells play crucial roles in MM development. We previously reported that BMSC-derived exosomes directly promote MM cell growth, whereas the other possible mechanisms for supporting MM progression by these exosomes are still not clear. Here, we investigated the effect of BMSC-derived exosomes on the MM BM cells with specific emphasis on myeloid-derived suppressor cells (MDSCs). BMSC-derived exosomes were able to be taken up by MM MDSCs and induced their expansion in vitro. Moreover, these exosomes directly induced the survival of MDSCs through activating STAT3 and STAT1 pathways and increasing the anti-apoptotic proteins Bcl-xL and Mcl-1. Inhibition of these pathways blocked the enhancement of MDSC survival. Furthermore, these exosomes increased the nitric oxide release from MM MDSCs and enhanced their suppressive activity on T cells. Taken together, our results demonstrate that BMSC-derived exosomes activate MDSCs in the BM through STAT3 and STAT1 pathways, leading to increased immunosuppression which favors MM progression.

  4. Redox activity and multiple copper(I) coordination of 2His-2Cys oligopeptide.

    Science.gov (United States)

    Choi, DongWon; Alshahrani, Aisha A; Vytla, Yashodharani; Deeconda, Manogna; Serna, Victor J; Saenz, Robert F; Angel, Laurence A

    2015-02-01

    Copper binding motifs with their molecular mechanisms of selective copper(I) recognition are essential molecules for acquiring copper ions, trafficking copper to specific locations and controlling the potentially damaging redox activities of copper in biochemical processes. The redox activity and multiple Cu(I) binding of an analog methanobactin peptide-2 (amb2) with the sequence acetyl-His1-Cys2-Tyr3-Pro4-His5-Cys6 was investigated using ion mobility-mass spectrometry (IM-MS) and UV-Vis spectrophotometry analyses. The Cu(II) titration of amb2 showed oxidation of amb2 via the formation of intra- and intermolecular Cys-Cys disulfide bridges and the multiple Cu(I) coordination by unoxidized amb2 or the partially oxidized dimer and trimer of amb2. The principal product of these reactions was [amb2 + 3Cu(I)](+) which probably coordinates the three Cu(I) ions via two bridging thiolate groups of Cys2 and Cys6 and the δN6 of the imidazole groups of His6, as determined by geometry optimized structures at the B3LYP/LanL2DZ level of theory. The products observed by IM-MS showed direct correlation to spectral changes associated with disulfide bond formation in the UV-Vis spectrophotometric study. The results show that IM-MS analysis is a powerful technique for unambiguously determining the major ion species produced during the redox and metal binding chemistry of oligopeptides.

  5. Bioequivalence of Two Intravenous Artesunate Products with Its Active Metabolite Following Single and Multiple Injections

    Directory of Open Access Journals (Sweden)

    Qigui Li

    2011-01-01

    Full Text Available In animal species and humans, artesunate (AS undergoes extensive and complex biotransformation to an active metabolite, dihydroartemisinin (DHA. The bioequivalence of two intravenous AS pharmaceutical products with 5% NaHCO3 (China Formulation or 0.3 M PBS (WRAIR Formulation was determined in rats in a two-formulation, two-period, and two-sequence crossover experimental design. Following single and multiple intravenous administrations, a series of blood samples was collected by using an automated blood sampler and drug concentrations were analyzed by LC-MS/MS. The 90% CI of the difference between the two intravenous formulations was contained within 80–125% of the geometric mean of pharmacokinetic parameters for AS and DHA in all animals dosed. Hematological effects were studied on days 1 and 3 after the final dosing, and a rapidly reversible hematological toxicity (significant reductions in reticulocyte levels was seen in the peripheral blood of the rats treated with each formulation. The results showed that bioequivalence with the parent compound and active metabolite was fulfilled in the 82.3–117.7% ranges of all parameters (AUC0–t, Cmax, concentration average and degree of fluctuation in the two-period and two-sequence crossover studies following single and repeated intravenous injections. For the metabolite, the equivalence was satisfied in most pharmacokinetic parameters tested due to the variability in the hydrolysis rate of AS to DHA. The WRAIR formulation of AS was considered to be bioequivalent to the Chinese formulation at steady-state according to the total drug exposure, in terms of both parent drug and active metabolite, rapidly reversal in reticulocyte decline, and extension of single and multiple administrations. Therefore, the parent drug and active metabolites should play similar important roles in the determination of efficacy and safety of the drug.

  6. Targeting of macrophage galactose-type C-type lectin (MGL) induces DC signaling and activation

    DEFF Research Database (Denmark)

    Napoletano, Chiara; Zizzari, Ilaria G; Rughetti, Aurelia;

    2012-01-01

    Dendritic cells (DCs) sense the microenvironment through several types of receptors recognizing pathogen-associated molecular patterns. In particular, C-type lectins, expressed by distinct subsets of DCs, recognize and internalize specific carbohydrate antigen in a Ca(2+) -dependent manner. Targe...

  7. Cinacalcet therapy in patients affected by primary hyperparathyroidism associated to Multiple Endocrine Neoplasia Syndrome type 1 (MEN1).

    Science.gov (United States)

    Giusti, Francesca; Cianferotti, Luisella; Gronchi, Giorgio; Cioppi, Federica; Masi, Laura; Faggiano, Antongiulio; Colao, Annamaria; Ferolla, Piero; Brandi, Maria Luisa

    2016-06-01

    Primary hyperparathyroidism is the main endocrinopathy associated with Multiple Endocrine Neoplasia type 1 syndrome. Cinacalcet is a calcimimetic agent licensed for the treatment of secondary hyperparathyroidism in patients with end-stage renal disease, and for the reduction of marked hypercalcemia in patients with parathyroid carcinoma and sporadic hyperparathyroidism requiring surgery but for whom parathyroidectomy is contraindicated. It may provide a medical alternative for the management of primary hyperparathyroidism in subjects affected by Multiple Endocrine Neoplasia type 1. In this longitudinal, intervention study, 33 MEN1 patients had been enrolled, 10 males and 23 females with a mean age of 40 ± 11.9 years, range 20-63. Primary hyperparathyroidism was the first clinical manifestation in 12 patients. All subjects commenced with Cinacalcet 30 mg/day, 22 patients starting therapy with calcimimetics as an alternative to surgery, and 11 patients opting for the medication after the onset of persistent post-surgical primary hyperparathyroidism. Duration of follow-up was 12 months. The results of this study show significant reductions in serum calcium. The changes in hormonal secretions of pituitary and gastroenteropancreatic glands were not significant, demonstrating the overall safety of this drug in this disease. Cinacalcet has been well tolerated by 28 patients, whereas five individuals complained of heartburn and grade 1 nausea, which did not prevent the completion of the study. In conclusion, Cinacalcet has resulted to be well tolerated and safe in patients with MEN1 syndrome and the calcium homeostasis was stabilized.

  8. [Application of multiple-branch prostheses in reconstruction of the aortic arch in DeBakey Type I aortic dissection].

    Science.gov (United States)

    Cherniavskiĭ, A M; Alsov, S A; Marchenko, A V; Smolianinov, K A; Sizov, G G; Zotov, A S

    2006-01-01

    Over the period from January 2002 to March 2005, a total of 78 patients were operated on for DeBakey type I aortic dissection. Of these, five patients underwent prosthetic reconstruction of the aortic arch and brachiocephalic arteries (BCA), performed with the help of the Dacron prosthesis Gelweave four-branch plexus Vascutek. The major indication for using this prosthesis was the extending of the dissection into the BC As, with various degree of obstruction thereof. The overwhelming majority of the patients were men (80 %). The patients' average age amounted to 44.3+/-5.6 years (ranging from 36 to 57 years). In three cases, the aortic dissection was of chronic course, with acute and subacute dissection being diagnosed in the remaining two cases. The median-sternotomy access, and additional approaches to the left and right common carotid arteries were used in order to carry out prosthetic reconstruction of the ascending branch, aortic arch, right subclavian artery, right common carotid artery (CCA) and left CCA with the help of the multiple-branch prosthesis. Protection of the brain consisted of craniocerebral hypothermia, hypothermal circulatory arrest in a combination with retrograde cerebral perfusions through the vena cava superior. The duration of the circulatory arrest averagely amounted to 59.2+/-4 min, with the mean time of artificial circulation equalling 230.6+/-19.7 min, and the time of aortic occlusion was 193.1+/-11 minutes. None of the patients developed either neurological or haemorrhagic complications postoperatively. Hence, the surgical technique using multiple-branch prostheses for prosthetic reconstruction of the aortic arch in type I aortic dissection with BCA obstruction proved to be effective and safe.

  9. Antibiotics that target mitochondria effectively eradicate cancer stem cells, across multiple tumor types: treating cancer like an infectious disease.

    Science.gov (United States)

    Lamb, Rebecca; Ozsvari, Bela; Lisanti, Camilla L; Tanowitz, Herbert B; Howell, Anthony; Martinez-Outschoorn, Ubaldo E; Sotgia, Federica; Lisanti, Michael P

    2015-03-10

    Here, we propose a new strategy for the treatment of early cancerous lesions and advanced metastatic disease, via the selective targeting of cancer stem cells (CSCs), a.k.a., tumor-initiating cells (TICs). We searched for a global phenotypic characteristic that was highly conserved among cancer stem cells, across multiple tumor types, to provide a mutation-independent approach to cancer therapy. This would allow us to target cancer stem cells, effectively treating cancer as a single disease of "stemness", independently of the tumor tissue type. Using this approach, we identified a conserved phenotypic weak point - a strict dependence on mitochondrial biogenesis for the clonal expansion and survival of cancer stem cells. Interestingly, several classes of FDA-approved antibiotics inhibit mitochondrial biogenesis as a known "side-effect", which could be harnessed instead as a "therapeutic effect". Based on this analysis, we now show that 4-to-5 different classes of FDA-approved drugs can be used to eradicate cancer stem cells, in 12 different cancer cell lines, across 8 different tumor types (breast, DCIS, ovarian, prostate, lung, pancreatic, melanoma, and glioblastoma (brain)). These five classes of mitochondrially-targeted antibiotics include: the erythromycins, the tetracyclines, the glycylcyclines, an anti-parasitic drug, and chloramphenicol. Functional data are presented for one antibiotic in each drug class: azithromycin, doxycycline, tigecycline, pyrvinium pamoate, as well as chloramphenicol, as proof-of-concept. Importantly, many of these drugs are non-toxic for normal cells, likely reducing the side effects of anti-cancer therapy. Thus, we now propose to treat cancer like an infectious disease, by repurposing FDA-approved antibiotics for anti-cancer therapy, across multiple tumor types. These drug classes should also be considered for prevention studies, specifically focused on the prevention of tumor recurrence and distant metastasis. Finally, recent

  10. Understanding physical activity intentions among French Canadians with type 2 diabetes: an extension of Ajzen's theory of planned behaviour

    Directory of Open Access Journals (Sweden)

    Godin Gaston

    2009-06-01

    Full Text Available Abstract Background Regular physical activity is considered a cornerstone for managing type 2 diabetes. However, in Canada, most individuals with type 2 diabetes do not meet national physical activity recommendations. When designing a theory-based intervention, one should first determine the key determinants of physical activity for this population. Unfortunately, there is a lack of information on this aspect among adults with type 2 diabetes. The purpose of this cross-sectional study is to fill this gap using an extended version of Ajzen's Theory of Planned Behavior (TPB as reference. Methods A total of 501 individuals with type 2 diabetes residing in the Province of Quebec (Canada completed the study. Questionnaires were sent and returned by mail. Results Multiple hierarchical regression analyses indicated that TPB variables explained 60% of the variance in intention. The addition of other psychosocial variables in the model added 7% of the explained variance. The final model included perceived behavioral control (β = .38, p Conclusion The findings suggest that interventions aimed at individuals with type 2 diabetes should ensure that people have the necessary resources to overcome potential obstacles to behavioral performance. Interventions should also favor the development of feelings of personal responsibility to exercise and promote the advantages of exercising for individuals with type 2 diabetes.

  11. Stat1 activation attenuates IL-6 induced Stat3 activity but does not alter apoptosis sensitivity in multiple myeloma

    Directory of Open Access Journals (Sweden)

    Dimberg Lina Y

    2012-07-01

    Full Text Available Abstract Background Multiple myeloma (MM is at present an incurable malignancy, characterized by apoptosis-resistant tumor cells. Interferon (IFN treatment sensitizes MM cells to Fas-induced apoptosis and is associated with an increased activation of Signal transducer and activator of transcription (Stat1. The role of Stat1 in MM has not been elucidated, but Stat1 has in several studies been ascribed a pro-apoptotic role. Conversely, IL-6 induction of Stat3 is known to confer resistance to apoptosis in MM. Methods To delineate the role of Stat1 in IFN mediated sensitization to apoptosis, sub-lines of the U-266-1970 MM cell line with a stable expression of the active mutant Stat1C were utilized. The influence of Stat1C constitutive transcriptional activation on endogenous Stat3 expression and activation, and the expression of apoptosis-related genes were analyzed. To determine whether Stat1 alone would be an important determinant in sensitizing MM cells to apoptosis, the U-266-1970-Stat1C cell line and control cells were exposed to high throughput compound screening (HTS. Results To explore the role of Stat1 in IFN mediated apoptosis sensitization of MM, we established sublines of the MM cell line U-266-1970 constitutively expressing the active mutant Stat1C. We found that constitutive nuclear localization and transcriptional activity of Stat1 was associated with an attenuation of IL-6-induced Stat3 activation and up-regulation of mRNA for the pro-apoptotic Bcl-2 protein family genes Harakiri, the short form of Mcl-1 and Noxa. However, Stat1 activation alone was not sufficient to sensitize cells to Fas-induced apoptosis. In a screening of > 3000 compounds including bortezomib, dexamethasone, etoposide, suberoylanilide hydroxamic acid (SAHA, geldanamycin (17-AAG, doxorubicin and thalidomide, we found that the drug response and IC50 in cells constitutively expressing active Stat1 was mainly unaltered. Conclusion We conclude that Stat1 alters IL-6

  12. Biochar as potential sustainable precursors for activated carbon production: Multiple applications in environmental protection and energy storage.

    Science.gov (United States)

    Tan, Xiao-Fei; Liu, Shao-Bo; Liu, Yun-Guo; Gu, Yan-Ling; Zeng, Guang-Ming; Hu, Xin-Jiang; Wang, Xin; Liu, Shao-Heng; Jiang, Lu-Hua

    2017-03-01

    There is a growing interest of the scientific community on production of activated carbon using biochar as potential sustainable precursors pyrolyzed from biomass wastes. Physical activation and chemical activation are the main methods applied in the activation process. These methods could have significantly beneficial effects on biochar chemical/physical properties, which make it suitable for multiple applications including water pollution treatment, CO2 capture, and energy storage. The feedstock with different compositions, pyrolysis conditions and activation parameters of biochar have significant influences on the properties of resultant activated carbon. Compared with traditional activated carbon, activated biochar appears to be a new potential cost-effective and environmentally-friendly carbon materials with great application prospect in many fields. This review not only summarizes information from the current analysis of activated biochar and their multiple applications for further optimization and understanding, but also offers new directions for development of activated biochar.

  13. Promoting physical activity participation among people with profound intellectual and multiple disabilities : An overview of practice-based knowledge

    NARCIS (Netherlands)

    van Alphen, Leentje; Waninge, Aly; van der Putten, Annette

    2016-01-01

    Aim: Promoting physical activity participation as part of the support of people with profound intellectual and multiple disabilities (PIMD) is important for the functioning of people with PIMD and their participation in daily activities. However, people with PIMD hardly participate in physical activ

  14. Environmental and Individual Correlates of Various Types of Physical Activity among Community-Dwelling Middle-Aged and Elderly Japanese

    Directory of Open Access Journals (Sweden)

    Yoshinobu Saito

    2013-05-01

    Full Text Available Recent studies have suggested the importance of the neighborhood environment in determining the specific type of physical activity. However, few studies on this topic have been undertaken in Japan. This study examined the association of three types of physical activity and their associations with individual and neighborhood environmental factors among middle-aged and elderly Japanese. Participants were 2,449 adults aged 40–69 living in Fujisawa city who had undergone health checkups and responded to our survey by mail. Individual factors, the International Physical Activity Questionnaire (long form, and its environmental module acted as inputs to the study. The adjusted odds ratios (ORs of high levels of moderate-to-vigorous intensity leisure-time physical activity (LTPA, walking for active recreation, and transportation were calculated in relation to individual and neighborhood environmental factors through multiple logistic regression models. Not working and good self-rated health were significantly associated with a higher level of each physical activity outcome. According to the adjusted ORs, higher educational attainment, higher economic status, good access to exercise facilities, and owning motor vehicles were associated with longer LTPA time. However, different sets of factors were associated with longer walking times for recreation and transportation. The results suggest that diverse individual and neighborhood environmental characteristics are associated with different physical activity outcomes. Therefore, customizing environments to become activity-friendly is necessary to increase physical activity effectively among middle-aged and elderly Japanese.

  15. The effect of psychometric variables in predicting physical activity behavior among diabetes mellitus type-2 patients

    Science.gov (United States)

    Gizaw, Abraham Tamirat; Abamecha Ababulgu, Fira; Abebe Gebretsadik, Lakew; Kiros Abraha, Getachew

    2017-01-01

    Background Diabetes mellitus type-2 (DMT-2), the most common endocrine disease in the world, is a major global public health-related issue. Diabetes mellitus is one of the most common non-communicable diseases globally, and there is substantial evidence that it is epidemic in many low- and middle-income countries. It is widely recognized that physical activity is important in preventing and treating DMT-2. The aim of this study was to identify predictors of physical activity among DMT-2 patients attending Jimma University Specialized Hospital (JUSH), Southwest Ethiopia. Methods A facility-based cross-sectional study was conducted in 2013 at JUSH, Southwest Ethiopia. A systematic random sampling technique was employed to select 322 diabetes patients. Data were collected using a structured questionnaire on interviewer-administered basis. A summary of descriptive statistics, and binary and multiple logistic regression analysis were computed to identify potential predictors of physical activity among diabetes mellitus patients. Results Among the 319, 70 (21%) engaged in the recommended physical activity (such as running, jogging, going to the gym, or brisk walking). Two hundred seventy-nine (87.5) of the respondents had adequate general knowledge of diabetes and 31.7% of the respondents had adequate general knowledge of physical activity. The likelihood of engaging in the recommended physical activity was associated with perceived barrier (odds ratio [OR]=0.58, 95% confidence interval, CI [0.56, 0.67]; p<0.000), perceived self-efficacy (OR=1.33, 95% CI [1.12, 1.57] p<0.001) and perceived benefit (OR=1.16 (95% CI [1.03, 1.29] p<0.000). Conclusion This study illustrated that practicing the recommended physical activities among DMT-2 patients was insufficient. Perceived barrier, perceived benefit and perceived self-efficacy became potential predictors of physical activity of DMT-2 patients. None of the socio-demographic factors affect the physical activity behavior of

  16. Oral activity of a nature-derived cyclic peptide for the treatment of multiple sclerosis.

    Science.gov (United States)

    Thell, Kathrin; Hellinger, Roland; Sahin, Emine; Michenthaler, Paul; Gold-Binder, Markus; Haider, Thomas; Kuttke, Mario; Liutkevičiūtė, Zita; Göransson, Ulf; Gründemann, Carsten; Schabbauer, Gernot; Gruber, Christian W

    2016-04-12

    Multiple sclerosis (MS) is the most common autoimmune disease affecting the central nervous system. It is characterized by auto-reactive T cells that induce demyelination and neuronal degradation. Treatment options are still limited and several MS medications need to be administered by parenteral application but are modestly effective. Oral active drugs such as fingolimod have been weighed down by safety concerns. Consequently, there is a demand for novel, especially orally active therapeutics. Nature offers an abundance of compounds for drug discovery. Recently, the circular plant peptide kalata B1 was shown to silence T-cell proliferation in vitro in an IL-2-dependent mechanism. Owing to this promising effect, we aimed to determine in vivo activity of the cyclotide [T20K]kalata B1 using the MS mouse model experimental autoimmune encephalomyelitis (EAE). Treatment of mice with the cyclotide resulted in a significant delay and diminished symptoms of EAE by oral administration. Cyclotide application substantially impeded disease progression and did not exhibit adverse effects. Inhibition of lymphocyte proliferation and the reduction of proinflammatory cytokines, in particular IL-2, distinguish the cyclotide from other marketed drugs. Considering their stable structural topology and oral activity, cyclotides are candidates as peptide therapeutics for pharmaceutical drug development for treatment of T-cell-mediated disorders.

  17. Activated microglia mediate axoglial disruption that contributes to axonal injury in multiple sclerosis.

    Science.gov (United States)

    Howell, Owain W; Rundle, Jon L; Garg, Anurag; Komada, Masayuki; Brophy, Peter J; Reynolds, Richard

    2010-10-01

    The complex manifestations of chronic multiple sclerosis (MS)are due in part to widespread axonal abnormalities that affect lesional and nonlesional areas in the central nervous system. We describe an association between microglial activation and axon/oligodendrocyte pathology at nodal and paranodal domains in normal-appearing white matter (NAWM) of MS cases and in experimental autoimmune encephalomyelitis (EAE). The extent of paranodal axoglial (neurofascin-155(+)/Caspr1(+)) disruption correlated with local microglial inflammation and axonal injury (expression of nonphosphorylated neurofilaments) in MS NAWM. These changes were independent of demyelinating lesions and did not correlate with the density of infiltrating lymphocytes. Similar axoglial alterations were seen in the subcortical white matter of Parkinson disease cases and in preclinical EAE, at a time point when there is microglial activation before the infiltration of immune cells. Disruption of the axoglial unit in adjuvant-immunized animals was reversible and coincided with the resolution of microglial inflammation; paranodal damage and microglial inflammation persisted in chronic EAE. Axoglial integrity could be preserved by the administration of minocycline, which inhibited microglial activation, in actively immunized animals. These data indicate that, in MS NAWM, permanent disruption to axoglial domains in an environment of microglial inflammation is an early indicator of axonal injury that likely affects nerve conduction and may contribute to physiologic dysfunction.

  18. Objectively Measured Physical Activity Is Associated with Brain Volumetric Measurements in Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Rachel E. Klaren

    2015-01-01

    Full Text Available Background. Little is known about physical activity and its association with volumes of whole brain gray matter and white matter and deep gray matter structures in persons with multiple sclerosis (MS. Purpose. This study examined the association between levels of physical activity and brain volumetric measures from magnetic resonance imaging (MRI in MS. Method. 39 persons with MS wore an accelerometer for a 7-day period and underwent a brain MRI. Normalized GM volume (NGMV, normalized WM volume (NWMV, and deep GM structures were calculated from 3D T1-weighted structural brain images. We conducted partial correlations (pr controlling for demographic and clinical variables. Results. Moderate-to-vigorous physical activity (MVPA was significantly associated with NGMV (pr=0.370, p<0.05, NWMV (pr=0.433, p<0.01, hippocampus (pr=0.499, p<0.01, thalamus (pr=0.380, p<0.05, caudate (pr=0.539, p<0.01, putamen (pr=0.369, p<0.05, and pallidum (pr=0.498, p<0.01 volumes, when controlling for sex, age, clinical course of MS, and Expanded Disability Status Scale score. There were no associations between sedentary and light physical activity with MRI outcomes. Conclusion. Our results provide the first evidence that MVPA is associated with volumes of whole brain GM and WM and deep GM structures that are involved in motor and cognitive functions in MS.

  19. Biologic Activity of Type I and Type II Fusobacterium nucleatum Isolates from Clinically Characterized Sites,

    Science.gov (United States)

    1984-07-26

    journal of choice is the Journal of Periodontology . 1 ncl JACK W. VINCENT as COL, DC Microbiology Branch SGRD-UDZ (19 Jul 84) TO COL Jack W. Vincent...Activitity of Type I and Type II Manuscript for Publication Fusobacterium nucleatum Isolates From Clinically Chatacterized Sites. 6. PERFORMING ONG...120) were obtained from subgingival plaque samples taken from 27 clinically characterized sites utilizing a selec- tive culture medium. All isolates

  20. Simultaneous acute shoulder arthritis and multiple mononeuropathy in a newly diagnosed type 2 diabetes patient - First case report.

    Science.gov (United States)

    Kotlęga, Dariusz; Gołąb-Janowska, Monika; Zaborowski, Grzegorz; Ciećwież, Sylwester; Nowacki, Przemysław

    Diabetes is a common disorder that leads to the musculoskeletal symptoms such as the shoulder arthritis. The involvement of peripheral nervous system is one of the troublesome for the patients as it provokes chronic sensory symptoms, lower motor neuron involvement and autonomic symptoms. In the course of the disease there has been several types of neuropathies described. A 41-year-old male patient was admitted to the internal medicine department because of the general weakness, malaise, polydypsia and polyuria since several days. The initial blood glucose level was 780mg/dl. During the first day the continuous insulin infusion was administered. On the next day when he woke up, the severe pain in the right shoulder with limited movement, right upper extremity weakness and burning pain in the radial aspect of this extremity appeared. On examination right shoulder joint movement limitation was found with the muscle weakness and sensory symptoms in the upper limbs. The clinical picture indicated on the right shoulder arthritis and the peripheral nervous system symptoms such as the right musculocutaneous, supraspinatus, right radial nerve and left radial nerve damage. We present a first case report of simultaneous, acute involvement of the shoulder joint and multiple neuropathy in a patient with newly diagnosed type 2 diabetes, presumably in the state of ketoacidosis.

  1. Coexistence of multiple attractors and crisis route to chaos in autonomous third order Duffing-Holmes type chaotic oscillators

    Science.gov (United States)

    Kengne, J.; Njitacke Tabekoueng, Z.; Fotsin, H. B.

    2016-07-01

    We perform a systematic analysis of a system consisting of an autonomous third order Duffing-Holmes type chaotic oscillator recently introduced by Tamasevicius et al. (2009). In this type of oscillators, the symmetrical characteristics of the nonlinear component necessary for generating chaotic oscillations is synthesized by using a pair of semiconductor diodes connected in anti-parallel. Based on the Shockley diode equation and a judicious choice of state variables, we derive a smooth mathematical model (involving hyperbolic sine and cosine functions) for a better description of both the regular and chaotic dynamics of the oscillator. The bifurcation analysis shows that chaos is achieved via the classical period-doubling and symmetry restoring crisis scenarios. More interestingly, some regions of the parameter space corresponding to the coexistence of multiple attractors (e.g. coexistence of four different attractors for the same values of system parameters) are discovered. This striking phenomenon is unique and has not yet been reported previously in an electrical circuit (the universal Chua's circuit included, in spite the immense amount of related research work), and thus represents a meaningful contribution to the understanding of the behavior of nonlinear dynamical systems in general. Some PSpice simulations of the nonlinear dynamics of the oscillator are carried out to verify the theoretical analysis.

  2. Optimal priority ordering in PHP production of multiple part-types in a failure-prone machine

    Directory of Open Access Journals (Sweden)

    Ana Sánchez

    2009-12-01

    Full Text Available This note deals with the problem of minimising the expected sum of quadratic holding and shortage inventory costs when a single, failure-prone machine produces multiple part-types. Shu and Perkins (2001 introduce the problem and, by restricting the set of control policies to the class of prioritised hedging point (PHP policies, establish simple, analytical expressions for the optimal hedging points provided that the priority ordering of the part-types is given. However, the determination of an optimal priority ordering is left by the authors as an open question. This leaves an embedded sequencing problem which we focus on in this note. We define a lower bound for the problem, introduce a test bed for future developments, and propose three dynamic programming approaches (with or without the lower bound for determining the optimal priority orderings for the instances of the test bed. This is an initial step in a research project aimed at solving the optimal priority ordering problem, which will allow evaluating the performance of future heuristic and metaheuristic procedures.

  3. Shaping of action potentials by type I and type II large-conductance Ca²+-activated K+ channels.

    Science.gov (United States)

    Jaffe, D B; Wang, B; Brenner, R

    2011-09-29

    The BK channel is a Ca(2+) and voltage-gated conductance responsible for shaping action potential waveforms in many types of neurons. Type II BK channels are differentiated from type I channels by their pharmacology and slow gating kinetics. The β4 accessory subunit confers type II properties on BK α subunits. Empirically derived properties of BK channels, with and without the β4 accessory subunit, were obtained using a heterologous expression system under physiological ionic conditions. These data were then used to study how BK channels alone (type I) and with the accessory β4 subunit (type II) modulate action potential properties in biophysical neuron models. Overall, the models support the hypothesis that it is the slower kinetics provided by the β4 subunit that endows the BK channel with type II properties, which leads to broadening of action potentials and, secondarily, to greater recruitment of SK channels reducing neuronal excitability. Two regions of parameter space distinguished type II and type I effects; one where the range of BK-activating Ca(2+) was high (>20 μM) and the other where BK-activating Ca(2+) was low (∼0.4-1.2 μM). The latter required an elevated BK channel density, possibly beyond a likely physiological range. BK-mediated sharpening of the spike waveform associated with the lack of the β4 subunit was sensitive to the properties of voltage-gated Ca(2+) channels due to electrogenic effects on spike duration. We also found that depending on Ca(2+) dynamics, type II BK channels may have the ability to contribute to the medium AHP, a property not generally ascribed to BK channels, influencing the frequency-current relationship. Finally, we show how the broadening of action potentials conferred by type II BK channels can also indirectly increase the recruitment of SK-type channels decreasing the excitability of the neuron.

  4. Prioritising Marketing Activities in Different Types of Marketing Functions

    DEFF Research Database (Denmark)

    Martensen, Anne; Mouritsen, Jan

    2016-01-01

    performance (BP) and top management's respect. An empirical survey identifies four types of MFs: (1) the broad spectrum; (2) the hesitant; (3) the traditional and (4) the market-creating. Findings show that for each of the four types, the effect of investing in a particular role varies: all roles......Marketing functions (MFs) differ in how they practise marketing roles. The purpose of this article is to differentiate between MFs that practice marketing roles in a particular manner and then study how these different types of MFs differ with regard to the marketing roles’ effect on business...... are not equally important to practise. Moreover, all roles are not equally important to all marketing functions, but depend on the marketing function's unique starting point. Since MFs differ, relevant investments in marketing roles also differ, making it beneficial to prioritise them. However, management...

  5. Sieving treatment biomarkers from blood gene-expression profiles: a pharmacogenomic update on two types of multiple sclerosis therapy.

    Science.gov (United States)

    Goertsches, Robert H; Zettl, Uwe K; Hecker, Michael

    2011-03-01

    Interferon-β (IFN-β) and glatiramer acetate are routinely used to inhibit disease activity in multiple sclerosis, but their mechanisms of action are incompletely understood. Individual treatment responses vary and candidate molecular markers that predict them have yet to be established. Why some patients respond poorly to a certain treatment while others respond well is addressed by the pharmacogenomic approach, which postulates that the molecular response to treatment correlates with the clinical effects, and thus seeks biological markers to estimate prognosis, guide therapy, comprehend the drugs' mechanisms of action and offer insights into disease pathogenesis. A poor clinical response can be owing to genetic variants in drug receptors or signaling components, or the appearance of neutralizing antibodies that interfere with the drug's binding efficacy. Independently, such mechanisms could lead to inadequate, that is to say unchanged, molecular responses, or exceedingly increased or decreased changes. By means of DNA microarray studies, various research groups endeavour to establish a clinically relevant relationship between the biological response to these drugs and treatment effects. Molecular profiles obtained in this way differ in the pattern and number of modulated genes, suggesting the existence of an individual 'drug-response fingerprint'. To further unravel the underlying regulatory interaction structure of the genes responsive to these immunotherapies represents a daunting but inevitable task. In this article, we focus on longitudinal ex vivo transcriptomic studies in multiple sclerosis and its therapy. We will discuss recurrently reported biomarker candidates, emphasizing those of immunologically meaning, and review studies with network module outputs.

  6. Context-Aware Active Authentication using Touch Gestures, Typing Patterns and Body Movement

    Science.gov (United States)

    2016-03-01

    15. SUBJECT TERMS Active Authentication, behavioral biometrics, keystroke dynamics 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT UU...CONTEXT-AWARE ACTIVE AUTHENTICATION USING TOUCH GESTURES, TYPING PATTERNS, AND BODY MOVEMENT LOUISIANA TECH UNIVERSITY MARCH 2016...TITLE AND SUBTITLE Context-Aware Active Authentication using Touch Gestures, Typing Patterns, and Body Movement 5a. CONTRACT NUMBER FA8750-13-2

  7. Design of a biomass-to-biorefinery logistics system through bio-inspired metaheuristic optimization considering multiple types of feedstocks

    Science.gov (United States)

    Trueba, Isidoro

    fossil fuels to biofuels. In many ways biomass is a unique renewable resource. It can be stored and transported relatively easily in contrast to renewable options such as wind and solar, which create intermittent electrical power that requires immediate consumption and a connection to the grid. This thesis presents two different models for the design optimization of a biomass-to-biorefinery logistics system through bio-inspired metaheuristic optimization considering multiple types of feedstocks. This work compares the performance and solutions obtained by two types of metaheuristic approaches; genetic algorithm and ant colony optimization. Compared to rigorous mathematical optimization methods or iterative algorithms, metaheuristics do not guarantee that a global optimal solution can be found on some class of problems. Problems with similar characteristics to the one presented in this thesis have been previously solved using linear programming, integer programming and mixed integer programming methods. However, depending on the type of problem, these mathematical or complete methods might need exponential computation time in the worst-case. This often leads to computation times too high for practical purposes. Therefore, this thesis develops two types of metaheuristic approaches for the design optimization of a biomass-to-biorefinery logistics system considering multiple types of feedstocks and shows that metaheuristics are highly suitable to solve hard combinatorial optimization problems such as the one addressed in this research work.

  8. Anti-diabetic activity of insulin-degrading enzyme inhibitors mediated by multiple hormones.

    Science.gov (United States)

    Maianti, Juan Pablo; McFedries, Amanda; Foda, Zachariah H; Kleiner, Ralph E; Du, Xiu Quan; Leissring, Malcolm A; Tang, Wei-Jen; Charron, Maureen J; Seeliger, Markus A; Saghatelian, Alan; Liu, David R

    2014-07-03

    Despite decades of speculation that inhibiting endogenous insulin degradation might treat type-2 diabetes, and the identification of IDE (insulin-degrading enzyme) as a diabetes susceptibility gene, the relationship between the activity of the zinc metalloprotein IDE and glucose homeostasis remains unclear. Although Ide(-/-) mice have elevated insulin levels, they exhibit impaired, rather than improved, glucose tolerance that may arise from compensatory insulin signalling dysfunction. IDE inhibitors that are active in vivo are therefore needed to elucidate IDE's physiological roles and to determine its potential to serve as a target for the treatment of diabetes. Here we report the discovery of a physiologically active IDE inhibitor identified from a DNA-templated macrocycle library. An X-ray structure of the macrocycle bound to IDE reveals that it engages a binding pocket away from the catalytic site, which explains its remarkable selectivity. Treatment of lean and obese mice with this inhibitor shows that IDE regulates the abundance and signalling of glucagon and amylin, in addition to that of insulin. Under physiological conditions that augment insulin and amylin levels, such as oral glucose administration, acute IDE inhibition leads to substantially improved glucose tolerance and slower gastric emptying. These findings demonstrate the feasibility of modulating IDE activity as a new therapeutic strategy to treat type-2 diabetes and expand our understanding of the roles of IDE in glucose and hormone regulation.

  9. The effects of cannabidiol and its synergism with bortezomib in multiple myeloma cell lines. A role for transient receptor potential vanilloid type-2.

    Science.gov (United States)

    Morelli, Maria Beatrice; Offidani, Massimo; Alesiani, Francesco; Discepoli, Giancarlo; Liberati, Sonia; Olivieri, Attilio; Santoni, Matteo; Santoni, Giorgio; Leoni, Pietro; Nabissi, Massimo

    2014-06-01

    Multiple myeloma (MM) is a plasma cell (PC) malignancy characterised by the accumulation of a monoclonal PC population in the bone marrow (BM). Cannabidiol (CBD) is a non-psychoactive cannabinoid with antitumoural activities, and the transient receptor potential vanilloid type-2 (TRPV2) channel has been reported as a potential CBD receptor. TRPV2 activation by CBD decreases proliferation and increases susceptibility to drug-induced cell death in human cancer cells. However, no functional role has been ascribed to CBD and TRPV2 in MM. In this study, we identified the presence of heterogeneous CD138+TRPV2+ and CD138+TRPV2- PC populations in MM patients, whereas only the CD138+ TRPV2- population was present in RPMI8226 and U266 MM cell lines. Because bortezomib (BORT) is commonly used in MM treatment, we investigated the effects of CBD and BORT in CD138+TRPV2- MM cells and in MM cell lines transfected with TRPV2 (CD138+TRPV2+). These results showed that CBD by itself or in synergy with BORT strongly inhibited growth, arrested cell cycle progression and induced MM cells death by regulating the ERK, AKT and NF-κB pathways with major effects in TRPV2+ cells. These data provide a rationale for using CBD to increase the activity of proteasome inhibitors in MM.

  10. Activation process in excitable systems with multiple noise sources: Large number of units

    CERN Document Server

    Franović, Igor; Todorović, Kristina; Kostić, Srđan; Burić, Nikola

    2015-01-01

    We study the activation process in large assemblies of type II excitable units whose dynamics is influenced by two independent noise terms. The mean-field approach is applied to explicitly demonstrate that the assembly of excitable units can itself exhibit macroscopic excitable behavior. In order to facilitate the comparison between the excitable dynamics of a single unit and an assembly, we introduce three distinct formulations of the assembly activation event. Each formulation treats different aspects of the relevant phenomena, including the threshold-like behavior and the role of coherence of individual spikes. Statistical properties of the assembly activation process, such as the mean time-to-first pulse and the associated coefficient of variation, are found to be qualitatively analogous for all three formulations, as well as to resemble the results for a single unit. These analogies are shown to derive from the fact that global variables undergo a stochastic bifurcation from the stochastically stable fix...

  11. Early-type stars in the young open cluster NGC 2244 and in the Mon OB2 association I. The multiplicity of O-type stars

    CERN Document Server

    Mahy, L; Rauw, G; Gosset, E; De Becker, M; Sana, H; Eenens, P

    2009-01-01

    Aims. We present the results obtained from a long-term spectroscopic campaign devoted to the multiplicity of O-type stars in the young open cluster NGC2244 and in the Mon OB2 association. Methods. Our spectroscopic monitoring was performed over several years, allowing us to probe different time-scales. For each star, several spectral diagnostic tools are applied, in order to search for line shifts and profile variations. We also measure the projected rotational velocity and revisit the spectral classification. Results. In our sample, several stars were previously considered as spectroscopic binaries, though only a few scattered observations were available. Our results now reveal a more complex situation. Our study identifies two new spectroscopic binaries (HD46149 in NGC2244 and HD46573 in MonOB2). The first object is a long-period double-lined spectroscopic binary, though the exact value of its period remains uncertain and the second object is classified as an SB1 system with a period of about 10.67 days but...

  12. Interferon Type I Driven Immune Activation in Generalized Autoimmune Diseases

    NARCIS (Netherlands)

    Z. Brkić (Zana)

    2013-01-01

    textabstractThis thesis describes research performed on several generalized autoimmune diseases with the main focus on primary Sjögren’s syndrome. Interferon type I has been implicated in the pathogenesis of these diseases and will be introduced in this chapter together with other important immune f

  13. Modulation of anticipatory postural activity for multiple conditions of a whole-body pointing task.

    Science.gov (United States)

    Tolambiya, A; Chiovetto, E; Pozzo, T; Thomas, E

    2012-05-17

    This is a study on associated postural activities during the anticipatory segments of a multijoint movement. Several previous studies have shown that they are task dependant. The previous studies, however, have mostly been limited in demonstrating the presence of modulation for one task condition, that is, one aspect such as the distance of the target or the direction of reaching. Real-life activities like whole-body pointing, however, can vary in several ways. How specific is the adaptation of the postural activities for the diverse possibilities of a whole-body pointing task? We used a classification paradigm to answer this question. We examined the anticipatory postural electromyograms for four different types of whole-body pointing tasks. The presence of task-dependent modulations in these signals was probed by performing four-way classification tests using a support vector machine (SVM). The SVM was able to achieve significantly higher than chance performance in correctly predicting the movements at hand (Chance performance 25%). Using only anticipatory postural muscle activity, the correct movement at hand was predicted with a mean rate of 62%. Because this is 37% above chance performance, it suggests the presence of postural modulation for diverse conditions. The anticipatory activities consisted of both activations and deactivations. Movement prediction with the use of the activating muscles was significantly better than that obtained with the deactivating muscles. This suggests that more specific modulations for the movement at hand take place through activation, whereas the deactivation is more general. The study introduces a new method for investigating adaptations in motor control. It also sheds new light on the quantity and quality of information available in the feedforward segments of a voluntary multijoint motor activity.

  14. Insights into mechanism of glucokinase activation: observation of multiple distinct protein conformations.

    Science.gov (United States)

    Liu, Shenping; Ammirati, Mark J; Song, Xi; Knafels, John D; Zhang, Jeff; Greasley, Samantha E; Pfefferkorn, Jeffrey A; Qiu, Xiayang

    2012-04-20

    Human glucokinase (GK) is a principal regulating sensor of plasma glucose levels. Mutations that inactivate GK are linked to diabetes, and mutations that activate it are associated with hypoglycemia. Unique kinetic properties equip GK for its regulatory role: although it has weak basal affinity for glucose, positive cooperativity in its binding of glucose causes a rapid increase in catalytic activity when plasma glucose concentrations rise above euglycemic levels. In clinical trials, small molecule GK activators (GKAs) have been efficacious in lowering plasma glucose and enhancing glucose-stimulated insulin secretion, but they carry a risk of overly activating GK and causing hypoglycemia. The theoretical models proposed to date attribute the positive cooperativity of GK to the existence of distinct protein conformations that interconvert slowly and exhibit different affinities for glucose. Here we report the respective crystal structures of the catalytic complex of GK and of a GK-glucose complex in a wide open conformation. To assess conformations of GK in solution, we also carried out small angle x-ray scattering experiments. The results showed that glucose dose-dependently converts GK from an apo conformation to an active open conformation. Compared with wild type GK, activating mutants required notably lower concentrations of glucose to be converted to the active open conformation. GKAs decreased the level of glucose required for GK activation, and different compounds demonstrated distinct activation profiles. These results lead us to propose a modified mnemonic model to explain cooperativity in GK. Our findings may offer new approaches for designing GKAs with reduced hypoglycemic risk.

  15. High-contrast active cavitation imaging technique based on multiple bubble wavelet transform.

    Science.gov (United States)

    Lu, Shukuan; Xu, Shanshan; Liu, Runna; Hu, Hong; Wan, Mingxi

    2016-08-01

    In this study, a unique method that combines the ultrafast active cavitation imaging technique with multiple bubble wavelet transform (MBWT) for improving cavitation detection contrast was presented. The bubble wavelet was constructed by the modified Keller-Miksis equation that considered the mutual effect among bubbles. A three-dimensional spatial model was applied to simulate the spatial distribution of multiple bubbles. The effects of four parameters on the signal-to-noise ratio (SNR) of cavitation images were evaluated, including the following: initial radii of bubbles, scale factor in the wavelet transform, number of bubbles, and the minimum inter-bubble distance. And the other two spatial models and cavitation bubble size distributions were introduced in the MBWT method. The results suggested that in the free-field experiments, the averaged SNR of images acquired by the MBWT method was improved by 7.16 ± 0.09 dB and 3.14 ± 0.14 dB compared with the values of images acquired by the B-mode and single bubble wavelet transform (SBWT) methods. In addition, in the tissue experiments, the averaged cavitation-to-tissue ratio of cavitation images acquired by the MBWT method was improved by 4.69 ± 0.25 dB and 1.74± 0.29 dB compared with that of images acquired by B-mode and SBWT methods.

  16. Written justifications to multiple-choice concept questions during active learning in class

    Science.gov (United States)

    Koretsky, Milo D.; Brooks, Bill J.; Higgins, Adam Z.

    2016-07-01

    Increasingly, instructors of large, introductory STEM courses are having students actively engage during class by answering multiple-choice concept questions individually and in groups. This study investigates the use of a technology-based tool that allows students to answer such questions during class. The tool also allows the instructor to prompt students to provide written responses to justify the selection of the multiple-choice answer that they have chosen. We hypothesize that prompting students to explain and elaborate on their answer choices leads to greater focus and use of normative scientific reasoning processes, and will allow them to answer questions correctly more often. The study contains two parts. First, a crossover quasi-experimental design is employed to determine the influence of asking students to individually provide written explanations (treatment condition) of their answer choices to 39 concept questions as compared to students who do not. Second, we analyze a subset of the questions to see whether students identify the salient concepts and use appropriate reasoning in their explanations. Results show that soliciting written explanations can have a significant influence on answer choice and, when it does, that influence is usually positive. However, students are not always able to articulate the correct reason for their answer.

  17. Statins Increase Plasminogen Activator Inhibitor Type 1 Gene Transcription through a Pregnane X Receptor Regulated Element.

    Directory of Open Access Journals (Sweden)

    Frederick M Stanley

    Full Text Available Plasminogen activator inhibitor type 1 (PAI-1 is a multifunctional protein that has important roles in inflammation and wound healing. Its aberrant regulation may contribute to many disease processes such as heart disease. The PAI-1 promoter is responsive to multiple inputs including cytokines, growth factors, steroids and oxidative stress. The statin drugs, atorvastatin, mevastatin and rosuvastatin, increased basal and stimulated expression of the PAI-1 promoter 3-fold. A statin-responsive, nuclear hormone response element was previously identified in the PAI-1 promoter, but it was incompletely characterized. We characterized this direct repeat (DR of AGGTCA with a 3-nucleotide spacer at -269/-255 using deletion and directed mutagenesis. Deletion or mutation of this element increased basal transcription from the promoter suggesting that it repressed PAI-1 transcription in the unliganded state. The half-site spacing and the ligand specificity suggested that this might be a pregnane X receptor (PXR responsive element. Computational molecular docking showed that atorvastatin, mevastatin and rosuvastatin were structurally compatible with the PXR ligand-binding pocket in its agonist conformation. Experiments with Gal4 DNA binding domain fusion proteins showed that Gal4-PXR was activated by statins while other DR + 3 binding nuclear receptor fusions were not. Overexpression of PXR further enhanced PAI-1 transcription in response to statins. Finally, ChIP experiments using Halo-tagged PXR and RXR demonstrated that both components of the PXR-RXR heterodimer bound to this region of the PAI-1 promoter.

  18. The DNA copy number of human endogenous retrovirus-W (MSRV-type is increased in multiple sclerosis patients and is influenced by gender and disease severity.

    Directory of Open Access Journals (Sweden)

    Marta Garcia-Montojo

    Full Text Available BACKGROUND: Multiple sclerosis is an autoimmune disease more prevalent in women than in men. Multiple Sclerosis Associated Retrovirus element (MSRV is a member of type-W endogenous retrovirus family (HERV-W, known to be associated to MS. Most HERVs are unable to replicate but MSRV expression associated with reverse-transcriptase activity in MS would explain reported DNA copy number increase in MS patients. A potential link between HERV-W copies on chromosome X and gender differential prevalence has been suggested. The present study addresses MSRV-type DNA load in relation with the gender differences and clinical status in MS and healthy controls. RESULTS: 178 MS patients (62.9% women and 124 controls (56.5% women were included. MSRV env load (copies/pg of DNA was analyzed by real time qPCR with specific primers and probe for its env gene, in DNA from peripheral blood mononuclear cells (PBMCs. MSRV load was more elevated in MS patients than in controls (p = 4.15e-7. MS women presented higher MSRV load than control women (p = 0.009 and MS men also had higher load than control men (p = 2.77e-6. Besides, women had higher levels than men, both among patients (p = 0.007 and controls (p = 1.24e-6. Concordantly, EDSS and MSSS scores were higher among female patients with an elevated MSRV load (p = 0.03 and p = 0.04, respectively. CONCLUSIONS: MSRV increases its copy number in PBMC of MS patients and particularly in women with high clinical scores. This may explain causes underlying the higher prevalence of MS in women. The association with the clinical severity calls for further investigations on MSRV load in PBMCs as a biomarker for MS.

  19. The Albano multiple-maar center (Rome, Italy): an active volcanic area since 70 ka

    Science.gov (United States)

    Freda, C.; Gaeta, M.; Karner, D. B.; Marra, F.; Renne, P. R.; Scarlato, P.; Taddeucci, J.

    2003-04-01

    The Albano multiple-maar center hosted the most recent activity of the Alban Hills Volcanic District. The determination of its petrochemical characteristics and its geochronology is therefore of great importance in order to evaluate the status of this volcanic area and to assess the possible volcanic hazard for Rome. Despite the detailed 40Ar/39Ar geochronologic history of the products of its activity, relatively poor information on the stratigraphy and the petrology of this volcanic center exists. In order to develop a detailed chronostratigraphy, petrology, and a more thorough knowledge of the eruptive mechanisms that characterized the recent activity of the Albano center, a joint research project is being conducted by scientists from the Istituto Nazionale di Geofisica e Vulcanologia, the University of California at Berkeley, and the Berkeley Geochronology Center. Here we have studied the most complete stratigraphic section located within the northern crater rim of Albano, where most of the products are exposed. We have investigated proximal and distal outcrops, in order to correlate them to the units identified in the northern crater rim section. We will present our recently acquired geochronologic and petrochemical data, which indicates magma chamber recharge associated with this <70 ka volcanism.

  20. In situ dimerization of multiple wild type and mutant zinc transporters in live cells using bimolecular fluorescence complementation.

    Science.gov (United States)

    Lasry, Inbal; Golan, Yarden; Berman, Bluma; Amram, Noy; Glaser, Fabian; Assaraf, Yehuda G

    2014-03-14

    Zinc transporters (ZnTs) facilitate zinc efflux and zinc compartmentalization, thereby playing a key role in multiple physiological processes and pathological disorders, presumed to be modulated by transporter dimerization. We recently proposed that ZnT2 homodimerization is the underlying basis for the dominant negative effect of a novel heterozygous G87R mutation identified in women producing zinc-deficient milk. To provide direct visual evidence for the in situ dimerization and function of multiple normal and mutant ZnTs, we applied here the bimolecular fluorescence complementation (BiFC) technique, which enables direct visualization of specific protein-protein interactions. BiFC is based upon reconstitution of an intact fluorescent protein including YFP when its two complementary, non-fluorescent N- and C-terminal fragments (termed YN and YC) are brought together by a pair of specifically interacting proteins. Homodimerization of ZnT1, -2, -3, -4, and -7 was revealed by high subcellular fluorescence observed upon co-transfection of non-fluorescent ZnT-YC and ZnT-YN; this homodimer fluorescence localized in the characteristic compartments of each ZnT. The validity of the BiFC assay in ZnT dimerization was further corroborated when high fluorescence was obtained upon co-transfection of ZnT5-YC and ZnT6-YN, which are known to form heterodimers. We further show that BiFC recapitulated the pathogenic role that ZnT mutations play in transient neonatal zinc deficiency. Zinquin, a fluorescent zinc probe applied along with BiFC, revealed the in situ functionality of ZnT dimers. Hence, the current BiFC-Zinquin technique provides the first in situ evidence for the dimerization and function of wild type and mutant ZnTs in live cells.

  1. Immune Potential of a Novel Multiple-epitope Vaccine to FMDV Type Asia 1 in Guinea Pigs and Sheep

    Institute of Scientific and Technical Information of China (English)

    Jun-jun Shao; Jing-feng Wang; Hui-yun Chang; Ji-xing Liu

    2011-01-01

    To develop a safe and efficient recombinant subunit vaccine to foot-and-mouth disease virus(FMDV)type Asia 1 in sheep,a tandem repeated multiple-epitope gene consisting of residues 137-160 and 197-211 of the VP1 gene of FMDV was designed and artificially synthesized.The biologically functional molecule,the ovine IgG heavy constant region(oIgG)as a protein carrier was introduced for design of the multiple-epitope recombinant vaccine and recombinant expression plasmids pET-30a-RE and pET-30a-RE-oIgG were successfully constructed.The recombinant proteins,RE and RE-oIgG,were expressed as a formation of inclusion bodies in E.coli.The immune potential of this vaccine regime in guinea pigs and sheep was evaluated.The results showed that IgG could significantly enhance the immune potential of antigenic epitopes.The recombinant protein RE-oIgG could not only elicit the high levels of neutralizing antibodies and lymphocytes proliferation responses in the vaccinated guinea pigs,but confer complete protection in guinea pigs against virus challenge.Although the recombinant protein RE could not confer protection in the vaccinated animals,it could delay the appearance of the clinical signs and reduce the severity of disease.Inspiringly,the titers of anti-FMDV neutralizing antibodies elicited in sheep vaccinated with RE-oIgG was significantly higher than that for the RE vaccination.Therefore,we speculated that this vaccine formulation may be a promising strategy for designing a novel vaccine against FMDV in the future.

  2. Extracellular polysaccharides produced by Ganoderma formosanum stimulate macrophage activation via multiple pattern-recognition receptors

    Directory of Open Access Journals (Sweden)

    Wang Cheng-Li

    2012-08-01

    Full Text Available Abstract Background The fungus of Ganoderma is a traditional medicine in Asia with a variety of pharmacological functions including anti-cancer activities. We have purified an extracellular heteropolysaccharide fraction, PS-F2, from the submerged mycelia culture of G. formosanum and shown that PS-F2 exhibits immunostimulatory activities. In this study, we investigated the molecular mechanisms of immunostimulation by PS-F2. Results PS-F2-stimulated TNF-α production in macrophages was significantly reduced in the presence of blocking antibodies for Dectin-1 and complement receptor 3 (CR3, laminarin, or piceatannol (a spleen tyrosine kinase inhibitor, suggesting that PS-F2 recognition by macrophages is mediated by Dectin-1 and CR3 receptors. In addition, the stimulatory effect of PS-F2 was attenuated in the bone marrow-derived macrophages from C3H/HeJ mice which lack functional Toll-like receptor 4 (TLR4. PS-F2 stimulation triggered the phosphorylation of mitogen-activated protein kinases JNK, p38, and ERK, as well as the nuclear translocation of NF-κB, which all played essential roles in activating TNF-α expression. Conclusions Our results indicate that the extracellular polysaccharides produced by G. formosanum stimulate macrophages via the engagement of multiple pattern-recognition receptors including Dectin-1, CR3 and TLR4, resulting in the activation of Syk, JNK, p38, ERK, and NK-κB and the production of TNF-α.

  3. Profiling of multiple signal pathway activities by multiplexing antibody and GFP-based translocation assays.

    Science.gov (United States)

    Henriksen, Ulla; Fog, Jacob; Loechel, Frosty; Praestegaard, Morten

    2008-08-01

    Multiplexing of GFP based and immunofluorescence translocation assays enables easy acquisition of multiple readouts from the same cell in a single assay run. Immunofluorescence assays monitor translocation, phosphorylation, and up/down regulation of endogenous proteins. GFP-based assays monitor translocation of stably expressed GFP-fusion proteins. Such assays may be multiplexed along (vertical), across (horizontal), and between (branch) signal pathways. Examples of these strategies are presented: 1) The MK2-GFP assay monitors translocation of MK2-GFP from the nucleus to the cytoplasm in response to stimulation of the p38 pathway. By applying different immunofluorescent assays to the MK2 assay, a multiplexed HCA system is created for deconvolution of p38 pathway activation including assay readouts for MK2, p38, NFkappaB, and c-Jun. 2) A method for evaluating GPCR activation and internalization in a single assay run has been established by multiplexing GFP-based internalization assays with immunofluorescence assays for downstream transducers of GPCR activity: pCREB (cAMP sensor), NFATc1 (Ca(2+) sensor), and ERK (G-protein activation). Activation of the AT1 receptor is given as an example. 3) Cell toxicity readouts can be linked to primary readouts of interest via acquisition of secondary parameters describing cellular morphology. This approach is used to flag cytotoxic compounds and deselect false positives. The ATF6 Redistribution assay is provided as an example. These multiplex strategies provide a unique opportunity to enhance HCA data quality and save time during drug discovery. From a single assay run, several assay readouts are obtained that help the user to deconvolute the mode of action of test compounds.

  4. P型多系统萎缩的MRI表现%MRI Features of Multiple System Atrophy P Type

    Institute of Scientific and Technical Information of China (English)

    邝岚琼; 王小宜; 邢妩; 廖伟华; 谢芳芳; 那伟

    2012-01-01

    Objective To analyze the MRI features of the multiple system atrophy ( MSA) P,in order to provide ima-geology basis for clinical diagnosis. Materials and Methods MRI findings in 9 patients with MSA P type( parkinsonism in dominant multiple system atrophy) in XiangYa Hospital were analyzed retrospectively. Results Of 9 patients, 6 had abnormal findings in putamen, 4 had putamen atrophy, 2 had the long T2 signal of the putamen edge ( fissure sign) , and 3 had the putamen diffuse little long T1 & T2 signals, and 4 had the very long T, & very short T2 signals in outer back of putamen. Moreover, among these 6 patients, there was one case merely featured in the putamen atrophy and one in the very long T1 & very short T2 signal in the outer back of putamen, and the other 4 cases were found the abnormal changes in a variety of core shell overlap there. There were 5 cases of brain stem abnormalities, one with cross sign, and four with the whole brain stem atrophy (two were found the little long T1 & T2 signal concerning symmetry of the cerebellum feet). Hemisphere abnormalities were found in 3 cases, 3 cases of them were the atrophy of both bilateral frontal temporal parietal oc-cipitals, 2 cases atrophy of bilateral frontal lobes. Cerebellar hemisphere atrophy was found in two cases. Cross sign was found in late MSA P type,and FLAIR sequences facilitate the detection of abnormal signal. Conclusion MRI facilitates the clinical diagnosis of MSA P type.%目的 分析P型多系统萎缩(multiple system atrophy,MSA)的MRI特征,为临床诊断提供影像学依据.资料与方法 回顾性分析经临床诊断为MSA-P型9例患者的常规MRI资料.结果 9例中,6例壳核有异常发现,其中壳核萎缩4例,壳核边缘长T2信号(裂隙征)2例,壳核弥漫性稍长T1、稍长T2信号3例,壳核后外侧极长T1、极短T2信号4例.6例中,单纯表现为壳核萎缩及壳核后外侧极长T1、极短T2信号各1例,余4例为多种壳核异常改变重叠出现.5例脑

  5. Direct Angiotensin II Type 2 Receptor Stimulation Ameliorates Insulin Resistance in Type 2 Diabetes Mice with PPARγ Activation

    DEFF Research Database (Denmark)

    Ohshima, Kousei; Mogi, Masaki; Jing, Fei;

    2012-01-01

    The role of angiotensin II type 2 (AT(2)) receptor stimulation in the pathogenesis of insulin resistance is still unclear. Therefore we examined the possibility that direct AT(2) receptor stimulation by compound 21 (C21) might contribute to possible insulin-sensitizing/anti-diabetic effects in ty...... 2 diabetes (T2DM) with PPARγ activation, mainly focusing on adipose tissue.......The role of angiotensin II type 2 (AT(2)) receptor stimulation in the pathogenesis of insulin resistance is still unclear. Therefore we examined the possibility that direct AT(2) receptor stimulation by compound 21 (C21) might contribute to possible insulin-sensitizing/anti-diabetic effects in type...

  6. Drosophila type IV collagen mutation associates with immune system activation and intestinal dysfunction.

    Science.gov (United States)

    Kiss, Márton; Kiss, András A; Radics, Monika; Popovics, Nikoletta; Hermesz, Edit; Csiszár, Katalin; Mink, Mátyás

    2016-01-01

    The basal lamina (BM) contains numerous components with a predominance of type IV collagens. Clinical manifestations associated with mutations of the human COL4A1 gene include perinatal cerebral hemorrhage and porencephaly, hereditary angiopathy, nephropathy, aneurysms and muscle cramps (HANAC), ocular dysgenesis, myopathy, Walker–Warburg syndrome and systemic tissue degeneration. In Drosophila, the phenotype associated with dominant temperature sensitive mutations of col4a1 include severe myopathy resulting from massive degradation of striated muscle fibers, and in the gut, degeneration of circular visceral muscle cells and epithelial cells following detachment from the BM. In order to determine the consequences of altered BMfunctions due to aberrant COL4A1 protein, we have carried out a series of tests using Drosophila DTS-L3 mutants from our allelic series of col4a1 mutations with confirmed degeneration of various cell types and lowest survival rate among the col4a1 mutant lines at restrictive temperature. Results demonstrated epithelial cell degeneration in the gut, shortened gut, enlarged midgut with multiple diverticulae, intestinal dysfunction and shortened life span. Midgut immunohistochemistry analyses confirmed altered expression and distribution of BM components integrin PSI and PSII alpha subunits, laminin gamma 1, and COL4A1 both in larvae and adults. Global gene expression analysis revealed activation of the effector AMP genes of the primary innate immune system including Metchnikowin, Diptericin, Diptericin B, and edin that preceded morphological changes. Attacin::GFP midgut expression pattern further supported these changes. An increase in ROS production and changes in gut bacterial flora were also noted and may have further enhanced an immune response. The phenotypic features of Drosophila col4a1 mutants confirmed an essential role for type IV collagen in maintaining epithelial integrity, gut morphology and intestinal function and suggest that

  7. Validation of Algorithms for Basal Insulin Rate Reductions in Type 1 Diabetic Patients Practising Physical Activity

    Science.gov (United States)

    2013-04-19

    Type 1 Diabetes With a Subcutaneous Insulin Pump; Adjustment of the Recommended Basal Insulin Flow Rate in the Event of Physical Activity; Adjustment of the Recommended Prandial Insulin in the Event of Physical Activity

  8. Inactivation of Sonic Hedgehog Signaling and Polydactyly in Limbs of Hereditary Multiple Malformation, a Novel Type of Talpid Mutant

    Science.gov (United States)

    Matsubara, Yoshiyuki; Nakano, Mikiharu; Kawamura, Kazuki; Tsudzuki, Masaoki; Funahashi, Jun-Ichi; Agata, Kiyokazu; Matsuda, Yoichi; Kuroiwa, Atsushi; Suzuki, Takayuki

    2016-01-01

    Hereditary Multiple Malformation (HMM) is a naturally occurring, autosomal recessive, homozygous lethal mutation found in Japanese quail. Homozygote embryos (hmm−/−) show polydactyly similar to talpid2 and talpid3 mutants. Here we characterize the molecular profile of the hmm−/− limb bud and identify the cellular mechanisms that cause its polydactyly. The hmm−/− limb bud shows a severe lack of sonic hedgehog (SHH) signaling, and the autopod has 4 to 11 unidentifiable digits with syn-, poly-, and brachydactyly. The Zone of Polarizing Activity (ZPA) of the hmm−/− limb bud does not show polarizing activity regardless of the presence of SHH protein, indicating that either the secretion pathway of SHH is defective or the SHH protein is dysfunctional. Furthermore, mesenchymal cells in the hmm−/− limb bud do not respond to ZPA transplanted from the normal limb bud, suggesting that signal transduction downstream of SHH is also defective. Since primary cilia are present in the hmm−/− limb bud, the causal gene must be different from talpid2 and talpid3. In the hmm−/− limb bud, a high amount of GLI3A protein is expressed and GLI3 protein is localized to the nucleus. Our results suggest that the regulatory mechanism of GLI3 is disorganized in the hmm−/− limb bud. PMID:28083533

  9. Eye Typing using Markov and Active Appearance Models

    DEFF Research Database (Denmark)

    Hansen, Dan Witzner; Hansen, John Paulin; Nielsen, Mads

    2002-01-01

    multi-modal interactions based on video tracking systems. Robust methods are needed to track the eyes using web cameras due to the poor image quality. A real-time tracking scheme using a mean-shift color tracker and an Active Appearance Model of the eye is proposed. It is possible from this model...

  10. The impact of mitoxantrone on neurological disability in active multiple sclerosis patients

    Directory of Open Access Journals (Sweden)

    Mesaroš Šarlota

    2004-01-01

    Full Text Available Several in vivo and in vitro studies showed that mitoxantrone (MTX, a novel anthracendione antineoplastic agent, had an immunomodulatory effect that suppressed humoral immunity, reduced T-cell numbers, lessened helper activity, enhanced suppressor function and had some positive effect on acute and chronic experimental allergic encephalomyelitis in rats. Up to now, several trials of therapy with MTX have been performed in patients with multiple sclerosis (MS. MTX has been recently shown to reduce disease activity, as expressed by reducing relapse rate and decreasing new, active MRI lesions, in a selected group of patients with active relapsing-remitting (RR MS. Furthermore, more recently, it has been demonstrated that MTX reduce neurological disability in secondary progressive MS. We designed the open-label clinical trial involving 35 MS patients with active disease in order to evaluate the long-term clinical effects of 6-months MTX treatment during a follow-up period of 20-46 months (mean, 30 months. The study comprised 35 patients, who met the Poser criteria for clinically definite MS. All patients were clinically treated at the Institute of Neurology, Clinical Centre of Serbia, Belgrade, during the period from March 1996 to August 2000. The neurological disability state was evaluated at the entry, every month until completion of the therapy and every six months until August 2000, by means of Kurtzke Expanded Disability Status Scale (EDSS score. All patients had active MS. The criteria for disease activity were: 1 at least 2 relapses within the previous 2 years, or 2 progression of at least 1.0 point on EDSS scale during the same period. The included patients did not receive immunosuppressive therapy six months prior to the entry. The patients were assigned to receive MTX 20 mg intravenously (iv per month and methylprednisolone 1g iv per month, over six months. The clinical characteristics and demographic data of patients included in the study

  11. Resveratrol as a novel agent for treatment of multiple myeloma with matrix metalloproteinase inhibitory activity

    Institute of Scientific and Technical Information of China (English)

    Chun-yan SUN; Yu HU; Tao GUO; Hua-fang WANG; Xiao-ping ZHANG; Wen-juan HE; Hao TAN

    2006-01-01

    Aim: To examine the in vitro antitumor activity of resveratrol against multiple myeloma (MM) cell lines (RPMI 8226, U266, and KM3), and the mechanisms involved. Methods: The growth inhibition of resveratrol was determined by 3-(4, 5-dimethyl-2-thiazyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. The effect of resveratrol on the apoptosis was investigated by combined annexin V-propidium iodide staining. The effect of resveratrol on the invasion through Matrigel matrix was detected by transwell invasion analyses. The activity of matrix metalloproteinase (MMP)-2 and -9 proteins were determined by gelatin zymography analysis. The expression of MMP-2, MMP-9, Bcl-2, Bcl-xL, XIAP and Bax protein were detected using Western blotting analysis. Results: Resveratrol inhibited proliferation of MM cells in a dose- and time-dependent manner. Incubation of MM cells with resveratrol resulted in apoptotic cell death. Resveratrol down-regulated the expression of the antiapoptotic proteins Bcl-2, Bcl-xL and XIAP and up-regulated the expression of the proapoptotic protein Bax. Furthermore, resveratrol inhibited invasion of RPMI 8226, U266, and KM3 cells with IC50 values of 64±8 μmol/L, 93±11 μmol/L, and 153±11 μmol/L, respectively. Resveratrol inhibited the constitutive expression of MMP-2 and -9 proteins of MM cells and suppressed its gelatinolytic activity. Conclusion: Resveratrol inhibits the proliferation of MM cells by inducing apoptotic cell death. Resveratrol also inhibits MM cell invasion. The inhibition of invasion may be associated with the attenuation of the enzymatic activities of MMP-2 and -9.

  12. Role of (68)Ga-DOTATATE PET/CT in patients with multiple endocrine neoplasia type 1 (MEN1).

    Science.gov (United States)

    Lastoria, Secondo; Marciello, Francesca; Faggiano, Antongiulio; Aloj, Luigi; Caracò, Corradina; Aurilio, Michela; D'Ambrosio, Laura; Di Gennaro, Francesca; Ramundo, Valeria; Camera, Luigi; De Luca, Leonardo; Fonti, Rosa; Napolitano, Vincenzo; Colao, Annamaria

    2016-06-01

    Multiple endocrine neoplasia type 1 (MEN1) is a hereditary syndrome predisposing to many endocrine and neuroendocrine tumors (NET). Conventional imaging (CI) cannot provide satisfactory results for all the different types of MEN1-related tumors. Objective of this prospective observational study was to evaluate the role of (68)Ga-DOTATATE PET/CT in MEN1 compared to CI. Diagnostic performance of (68)Ga-DOTATATE PET/CT for the detection of NET was evaluated as well as the prognostic role of SUVmax. Eighteen patients with genetically confirmed MEN1 were evaluated by (68)Ga-DOTATATE PET/CT, endoscopic ultrasounds, multidetector-row computed tomography, magnetic resonance imaging, and hormone/markers serum measurements. Four MEN1-related tumor sites (pancreas, pituitary, parathyroids, adrenals) were considered. Sensitivity and specificity of (68)Ga-DOTATATE PET/CT for the detection of NET were calculated. There was (68)Ga-DOTATATE PET/CT uptake in 11/11 patients with pancreatic lesions, in 9/12 with pituitary adenoma, in 5/15 with parathyroid enlargements, and in 5/7 with adrenal lesions. (68)Ga-DOTATATE PET/CT showed sensitivity and specificity of 100 and 100 % in pancreas, 75 and 83 % in pituitary, 28 and 100 % in parathyroids, and 62.5 and 100 % in adrenals, respectively. Compared with CI, no significant difference in sensitivity for pancreas, pituitary, and adrenals was found, while CI had a better sensitivity for parathyroids (p = 0.002). On the ROC analysis, progression of pancreatic lesions was significantly associated to SUVmax 68)Ga-DOTATATE PET/CT is greatly helpful in the work-up of MEN1 providing a panoramic view of MEN1-related lesions. There is also a prognostic role of (68)Ga-PET in patients with MEN1-pancreatic lesions.

  13. Classifying Multiple Types of Hand Motions Using Electrocorticography During Intraoperative Awake Craniotomy & Seizure Monitoring Processes - Case Studies

    Directory of Open Access Journals (Sweden)

    Tao eXie

    2015-10-01

    Full Text Available In this work, some case studies were conducted toclassify several kinds of hand motions from electrocorticography(ECoG signals during intraoperative awake craniotomy &extraoperative seizure monitoring processes. Four subjects (P1,P2 with intractable epilepsy during seizure monitoring and P3,P4 with brain tumor during awake craniotomy participatedin the experiments. Subjects performed three types of handmotions (Grasp, Thumb-finger motion and Index-finger motioncontralateral to the motor cortex covered with ECoG electrodes.Two methods were used for signal processing. Method I:autoregressive (AR model with burg method was applied toextract features, and additional waveform length (WL featurehas been considered, finally the linear discriminative analysis(LDA was used as the classifier. Method II: stationary subspaceanalysis (SSA was applied for data preprocessing, and thecommon spatial pattern (CSP was used for feature extractionbefore LDA decoding process. Applying method I, the threeclassaccuracy of P1□P4 were 90.17%, 96.00%, 91.77% and92.95% respectively. For method II, the three-class accuracy ofP1□P4 were 72.00%, 93.17%, 95.22% and 90.36% respectively.This study verified the possibility of decoding multiple handmotion types during an awake craniotomy, which is the firststep towards dexterous neuroprosthetic control during surgicalimplantation, in order to verify the optimal placement of electrodes.The accuracy during awake craniotomy was comparableto results during seizure monitoring. This study also indicatedthat ECoG was a promising approach for precise identificationof eloquent cortex during awake craniotomy, and might forma promising BCI system that could benefit both patients andneurosurgeons.

  14. Plasminogen activator inhibitor type 1 interacts with alpha3 subunit of proteasome and modulates its activity.

    Science.gov (United States)

    Boncela, Joanna; Przygodzka, Patrycja; Papiewska-Pajak, Izabela; Wyroba, Elzbieta; Osinska, Magdalena; Cierniewski, Czeslaw S

    2011-02-25

    Plasminogen activator inhibitor type-1 (PAI-1), a multifunctional protein, is an important physiological regulator of fibrinolysis, extracellular matrix homeostasis, and cell motility. Recent observations show that PAI-1 may also be implicated in maintaining integrity of cells, especially with respect to cellular proliferation or apoptosis. In the present study we provide evidence that PAI-1 interacts with proteasome and affects its activity. First, by using the yeast two-hybrid system, we found that the α3 subunit of proteasome directly interacts with PAI-1. Then, to ensure that the PAI-1-proteasome complex is formed in vivo, both proteins were coimmunoprecipitated from endothelial cells and identified with specific antibodies. The specificity of this interaction was evidenced after transfection of HeLa cells with pCMV-PAI-1 and coimmunoprecipitation of both proteins with anti-PAI-1 antibodies. Subsequently, cellular distribution of the PAI-1-proteasome complexes was established by immunogold staining and electron microscopy analyses. Both proteins appeared in a diffuse cytosolic pattern but also could be found in a dense perinuclear and nuclear location. Furthermore, PAI-1 induced formation of aggresomes freely located in endothelial cytoplasm. Increased PAI-1 expression abrogated degradation of degron analyzed after cotransfection of HeLa cells with pCMV-PAI-1 and pd2EGFP-N1 and prevented degradation of p53 as well as IκBα, as evidenced both by confocal microscopy and Western immunoblotting.

  15. Plasminogen Activator Inhibitor Type 1 Interacts with α3 Subunit of Proteasome and Modulates Its Activity*

    Science.gov (United States)

    Boncela, Joanna; Przygodzka, Patrycja; Papiewska-Pajak, Izabela; Wyroba, Elzbieta; Osinska, Magdalena; Cierniewski, Czeslaw S.

    2011-01-01

    Plasminogen activator inhibitor type-1 (PAI-1), a multifunctional protein, is an important physiological regulator of fibrinolysis, extracellular matrix homeostasis, and cell motility. Recent observations show that PAI-1 may also be implicated in maintaining integrity of cells, especially with respect to cellular proliferation or apoptosis. In the present study we provide evidence that PAI-1 interacts with proteasome and affects its activity. First, by using the yeast two-hybrid system, we found that the α3 subunit of proteasome directly interacts with PAI-1. Then, to ensure that the PAI-1-proteasome complex is formed in vivo, both proteins were coimmunoprecipitated from endothelial cells and identified with specific antibodies. The specificity of this interaction was evidenced after transfection of HeLa cells with pCMV-PAI-1 and coimmunoprecipitation of both proteins with anti-PAI-1 antibodies. Subsequently, cellular distribution of the PAI-1-proteasome complexes was established by immunogold staining and electron microscopy analyses. Both proteins appeared in a diffuse cytosolic pattern but also could be found in a dense perinuclear and nuclear location. Furthermore, PAI-1 induced formation of aggresomes freely located in endothelial cytoplasm. Increased PAI-1 expression abrogated degradation of degron analyzed after cotransfection of HeLa cells with pCMV-PAI-1 and pd2EGFP-N1 and prevented degradation of p53 as well as IκBα, as evidenced both by confocal microscopy and Western immunoblotting. PMID:21135093

  16. Synthetic activity indicators for M-type dwarf stars

    CERN Document Server

    Wedemeyer, Sven

    2015-01-01

    Here, we present a set of time-dependent 3D RMHD simulations of a M-dwarf star representative of AD Leo, which extend from the upper convection zone into the chromosphere. The 3D model atmospheres are characterized by a very dynamic and intermittent structure on small spatial and temporal scales and a wealth of physical processes, which by nature cannot be described by means of 1D static model atmospheres. Artificial observations of these models imply that a combination of complementary diagnostics such as Ca II lines and the continuum intensity from UV to millimeter wavelengths, probe various properties of the dynamics, thermal and magnetic structure of the photosphere and the chromosphere and thus provide measures of stellar activity, which can be compared to observations. The complicated magnetic field structure and its imprint in synthetic diagnostics may have important implications for the understanding and characterization of stellar activity and with it possibly for the evaluation of planetary habitabi...

  17. Hydration free energies using semiempirical quantum mechanical Hamiltonians and a continuum solvent model with multiple atomic-type parameters.

    Science.gov (United States)

    Anisimov, Victor M; Cavasotto, Claudio N

    2011-06-23

    To build the foundation for accurate quantum mechanical (QM) simulation of biomacromolecules in an aqueous environment, we undertook the optimization of the COnductor-like Screening MOdel (COSMO) atomic radii and atomic surface tension coefficients for different semiempirical Hamiltonians adhering to the same computational conditions recently followed in the simulation of biomolecular systems. This optimization was achieved by reproducing experimental hydration free energies of a set consisting of 507 neutral and 99 ionic molecules. The calculated hydration free energies were significantly improved by introducing a multiple atomic-type scheme that reflects different chemical environments. The nonpolar contribution was treated according to the scaled particle Claverie-Pierotti formalism. Separate radii and surface tension coefficient sets have been developed for AM1, PM3, PM5, and RM1 semiempirical Hamiltonians, with an average unsigned error for neutral molecules of 0.64, 0.66, 0.73, and 0.71 kcal/mol, respectively. Free energy calculation of each molecule took on average 0.5 s on a single processor. The new sets of parameters will enhance the quality of semiempirical QM calculations using COSMO in biomolecular systems. Overall, these results further extend the utility of QM methods to chemical and biological systems in the condensed phase.

  18. H∞ State Estimation for Discrete-Time Delayed Systems of the Neural Network Type With Multiple Missing Measurements.

    Science.gov (United States)

    Liu, Meiqin; Chen, Haiyang

    2015-12-01

    This paper investigates the H∞ state estimation problem for a class of discrete-time nonlinear systems of the neural network type with random time-varying delays and multiple missing measurements. These nonlinear systems include recurrent neural networks, complex network systems, Lur'e systems, and so on which can be described by a unified model consisting of a linear dynamic system and a static nonlinear operator. The missing phenomenon commonly existing in measurements is assumed to occur randomly by introducing mutually individual random variables satisfying certain kind of probability distribution. Throughout this paper, first a Luenberger-like estimator based on the imperfect output data is constructed to obtain the immeasurable system states. Then, by virtue of Lyapunov stability theory and stochastic method, the H∞ performance of the estimation error dynamical system (augmented system) is analyzed. Based on the analysis, the H∞ estimator gains are deduced such that the augmented system is globally mean square stable. In this paper, both the variation range and distribution probability of the time delay are incorporated into the control laws, which allows us to not only have more accurate models of the real physical systems, but also obtain less conservative results. Finally, three illustrative examples are provided to validate the proposed control laws.

  19. MULTIPASS, a rice R2R3-type MYB transcription factor, regulates adaptive growth by integrating multiple hormonal pathways.

    Science.gov (United States)

    Schmidt, Romy; Schippers, Jos H M; Mieulet, Delphine; Obata, Toshihiro; Fernie, Alisdair R; Guiderdoni, Emmanuel; Mueller-Roeber, Bernd

    2013-10-01

    Growth regulation is an important aspect of plant adaptation during environmental perturbations. Here, the role of MULTIPASS (OsMPS), an R2R3-type MYB transcription factor of rice, was explored. OsMPS is induced by salt stress and expressed in vegetative and reproductive tissues. Over-expression of OsMPS reduces growth under non-stress conditions, while knockdown plants display increased biomass. OsMPS expression is induced by abscisic acid and cytokinin, but is repressed by auxin, gibberellin and brassinolide. Growth retardation caused by OsMPS over-expression is partially restored by auxin application. Expression profiling revealed that OsMPS negatively regulates the expression of EXPANSIN (EXP) and cell-wall biosynthesis as well as phytohormone signaling genes. Furthermore, the expression of OsMPS-dependent genes is regulated by auxin, cytokinin and abscisic acid. Moreover, we show that OsMPS is a direct upstream regulator of OsEXPA4, OsEXPA8, OsEXPB2, OsEXPB3, OsEXPB6 and the endoglucanase genes OsGLU5 and OsGLU14. The multiple responses of OsMPS and its target genes to various hormones suggest an integrative function of OsMPS in the cross-talk between phytohormones and the environment to regulate adaptive growth.

  20. A survey of the high order multiplicity of nearby solar-type binary stars with Robo-AO

    CERN Document Server

    Riddle, Reed L; Mason, Brian D; Hartkopf, William I; Roberts,, Lewis C; Baranec, Christoph; Law, Nicholas M; Bui, Khanh; Burse, Mahesh P; Das, H K; Dekany, Richard G; Kulkarni, Shrinivas; Punnadi, Sujit; Ramaprakash, A N; Tendulkar, Shriharsh P

    2014-01-01

    We conducted a survey of nearby binary systems composed of main sequence stars of spectral types F and G in order to improve our understanding of the hierarchical nature of multiple star systems. Using Robo-AO, the first robotic adaptive optics instrument, we collected high angular resolution images with deep and well-defined detection limits in the SDSS $i'$ band. A total of 695 components belonging to 595 systems were observed. We prioritized observations of faint secondary components with separations over $10''$ to quantify the still poorly constrained frequency of their sub-systems. Of the 214 secondaries observed, 39 contain such subsystems; 19 of those were discovered with Robo-AO. The selection-corrected frequency of secondary sub-systems with periods from $10^{3.5}$ to $10^5$ days is 0.12$\\pm$0.03, the same as the frequency of such companions to the primary. Half of the secondary pairs belong to quadruple systems where the primary is also a close pair, showing that the presence of sub-systems in both ...

  1. Reinforcement of a plate weakened by multiple holes with several patches for different types of a plate-patch attachment

    CERN Document Server

    Zemlyanova, A Y

    2012-01-01

    The most general situation of the reinforcement of a plate with multiple holes by several patches is considered. There is no restriction on the number and the location of the patches. Two types of the patch attachment are considered: only along the boundary of the patch or both along the boundary of the patch and the boundaries of the holes which this patch covers. The unattached boundaries of the holes may be loaded with given in-plane stresses. The mechanical problem is reduced to the system of singular integral equations which can be further reduced to the system of Fredholm equations. A new numerical procedure for the solution of the system of singular integral equations is proposed in this paper. It can be observed that this procedure provides a noticeable improvement from the one presented in Zemlyanova \\cite{Zem2007}, Zemlyanova and Silvestrov \\cite{ZemSil2007}, \\cite{ZemSil2009} and allows to achieve a significantly better numerical convergence with less computational effort.

  2. RET gene mutations (genotype and phenotype) of multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma.

    Science.gov (United States)

    Krampitz, Geoffrey W; Norton, Jeffrey A

    2014-07-01

    The rapid technical advances in molecular biology and accelerating improvements in genomic and proteomic diagnostics have led to increasingly personalized strategies for cancer therapy. Such an approach integrates the genomic, proteomic, and molecular information unique to the individual to provide an accurate genetic diagnosis, molecular risk assessment, informed family counseling, therapeutic profiling, and early preventative management that best fits the particular needs of each patient. The discovery of mutations in the RET proto-oncogene resulting in variable onset and severity of multiple endocrine neoplasia type 2 (MEN2) was the first step in developing direct genetic testing for at-risk individuals. Patients with germline RET mutations may undergo risk assessment and appropriate intervention based on specific mutations. Moreover, family members of affected individuals receive counseling based on understanding of the genetic transmission of the disease. Increasingly, clinicians are able to make therapeutic choices guided by an informative biomarker code. Improvements in detection and management of patients with MEN2 resulting from understanding of the RET proto-oncogene are evidence of the benefits of personalized cancer medicine. This review describes the discovery of the RET proto-oncogene, the association between genotype and phenotype, and the role of mutation analysis on diagnosis and treatment of MEN2.

  3. Multiple {gamma}-glutamylation: A novel type of post-translational modification in a diapausing Artemia cyst protein

    Energy Technology Data Exchange (ETDEWEB)

    Hasegawa, Mai [Bioscience Course, Graduate School of Science and Technology, Niigata University, 2-8050 Ikarashi, Nishi-Ku, Niigata 950-2181 (Japan); Ikeda, Yuka [Institute of High Polymer Research, Faculty of Textile Science and Technology, Shinshu University, 3-15-1, Tokida, Ueda 386-8567 (Japan); Kanzawa, Hideaki [Department of Biology, Faculty of Science, Niigata University, 2-8050 Ikarashi, Nishi-Ku, Niigata 950-2181 (Japan); Sakamoto, Mika [Bioscience Course, Graduate School of Science and Technology, Niigata University, 2-8050 Ikarashi, Nishi-Ku, Niigata 950-2181 (Japan); Goto, Mina [Department of Biology, Faculty of Science, Niigata University, 2-8050 Ikarashi, Nishi-Ku, Niigata 950-2181 (Japan); Tsunasawa, Susumu [Analytical and Measuring Instruments Division, Shimadzu Corporation, Nishinokyo Kuwabaracho 1, Nakagyo-Ku, Kyoto 604-8511 (Japan); Uchiumi, Toshio, E-mail: uchiumi@bio.sc.niigata-u.ac.jp [Bioscience Course, Graduate School of Science and Technology, Niigata University, 2-8050 Ikarashi, Nishi-Ku, Niigata 950-2181 (Japan); Department of Biology, Faculty of Science, Niigata University, 2-8050 Ikarashi, Nishi-Ku, Niigata 950-2181 (Japan); Odani, Shoji [Bioscience Course, Graduate School of Science and Technology, Niigata University, 2-8050 Ikarashi, Nishi-Ku, Niigata 950-2181 (Japan); Department of Biology, Faculty of Science, Niigata University, 2-8050 Ikarashi, Nishi-Ku, Niigata 950-2181 (Japan)

    2010-03-26

    A highly hydrophilic, glutamate-rich protein was identified in the aqueous phenol extract from the cytosolic fraction of brine shrimp (Artemia franciscana) diapausing cysts and termed Artemia phenol soluble protein (PSP). Mass spectrometric analysis revealed the presence of many protein peaks around m/z 11,000, separated by 129 atomic mass units; this value corresponds to that of glutamate, which is strongly suggestive of heterogeneous polyglutamylation. Polyglutamylation has long been known as the functionally important post-translational modification of tubulins, which carry poly(L-glutamic acid) chains of heterogeneous length branching off from the main chain at the {gamma}-carboxy groups of a few specific glutamate residues. In Artemia PSP, however, Edman degradation of enzymatic peptides revealed that at least 13, and presumably 16, glutamate residues were modified by the attachment of a single L-glutamate, representing a hitherto undescribed type of post-translational modification: namely, multiple {gamma}-glutamylation or the addition of a large number of glutamate residues along the polypeptide chain. Although biological significance of PSP and its modification is yet to be established, suppression of in vitro thermal aggregation of lactate dehydrogenase by glutamylated PSP was observed.

  4. A parasite-derived 68-mer peptide ameliorates autoimmune disease in murine models of Type 1 diabetes and multiple sclerosis

    Science.gov (United States)

    Lund, Maria E.; Greer, Judith; Dixit, Aakanksha; Alvarado, Raquel; McCauley-Winter, Padraig; To, Joyce; Tanaka, Akane; Hutchinson, Andrew T.; Robinson, Mark W.; Simpson, Ann M.; O’Brien, Bronwyn A.; Dalton, John P.; Donnelly, Sheila

    2016-01-01

    Helminth parasites secrete molecules that potently modulate the immune responses of their hosts and, therefore, have potential for the treatment of immune-mediated human diseases. FhHDM-1, a 68-mer peptide secreted by the helminth parasite Fasciola hepatica, ameliorated disease in two different murine models of autoimmunity, type 1 diabetes and relapsing-remitting immune-mediated demyelination. Unexpectedly, FhHDM-1 treatment did not affect the proliferation of auto-antigen specific T cells or their production of cytokines. However, in both conditions, the reduction in clinical symptoms was associated with the absence of immune cell infiltrates in the target organ (islets and the brain tissue). Furthermore, after parenteral administration, the FhHDM-1 peptide interacted with macrophages and reduced their capacity to secrete pro-inflammatory cytokines, such as TNF and IL-6. We propose this inhibition of innate pro-inflammatory immune responses, which are central to the initiation of autoimmunity in both diseases, prevented the trafficking of autoreactive lymphocytes from the periphery to the site of autoimmunity (as opposed to directly modulating their function per se), and thus prevented tissue destruction. The ability of FhHDM-1 to modulate macrophage function, combined with its efficacy in disease prevention in multiple models, suggests that FhHDM-1 has considerable potential as a treatment for autoimmune diseases. PMID:27883079

  5. Multiple system atrophy of the cerebellar type (MSA-C) with concomitant beta-amyloid and tau pathology.

    Science.gov (United States)

    Bujan, Bartosz; Hofer, Markus J; Oertel, Wolfgang H; Pagenstecher, Axel; Bürk, Katrin

    2013-01-01

    Multiple system atrophy (MSA) is a rapidly progressive sporadic α-synucleinopathy with adult onset characterized by progressive cerebellar ataxia, basal ganglia symptoms, autonomic dysfunction and pyramidal tract signs. While full-blown dementia is considered an exclusion criterion according to Consensus Guidelines, mild cognitive deficits such as fronto-executive dysfunction have been reported in some MSA individuals. However, the underlying anatomic correlate still has to be elucidated. We here report a 74-year-old patient with a clinical diagnosis of "probable MSA of the cerebellar type (MSA-C)" who developed pronounced clinical symptoms of fronto-executive dysfunction. Neuropathologic investigations revealed (1) numerous glial cytoplasmic inclusions (GCI) in the putamen, mesencephalon and cerebellum, (2) pronounced betaamyloid pathology in the frontal lobe and (3) mild hippocampal τ-pathology. In this patient, fronto-executive dysfunction can easily be explained by frontal degeneration typical for AD. These findings challenge the concept of cognitive dysfunction as a core feature of MSA as long as concomitant pathology other than MSA has not been reliably excluded by post mortem analysis.

  6. Cucurbitacin B exerts anti-cancer activities in human multiple myeloma cells in vitro and in vivo by modulating multiple cellular pathways

    Science.gov (United States)

    Huang, Ning; Zhong, Yueling; Zeng, Ting; Wei, Rong; Wu, Zhongjun; Xiao, Cui; Cao, Xiaohua; Li, Minhui; Li, Limei; Han, Bin; Yu, Xiaoping; Li, Hua; Zou, Qiang

    2017-01-01

    Cucurbitacin B (CuB), a triterpenoid compound isolated from the stems of Cucumis melo, has long been used to treat hepatitis and hepatoma in China. Although its remarkable anti-cancer activities have been reported, the mechanism by which it achieves this therapeutic activity remains unclear. This study was designed to investigate the molecular mechanisms by which CuB inhibits cancer cell proliferation. Our results indicate that CuB is a novel inhibitor of Aurora A in multiple myeloma (MM) cells, arresting cells in the G2/M phase. CuB also inhibited IL-10-induced STAT3 phosphorylation, synergistically increasing the anti-tumor activity of Adriamycin in vitro. CuB induced dephosphorylation of cofilin, resulting in the loss of mitochondrial membrane potential, release of cytochrome c, and activation of caspase-8. CuB inhibited MM tumor growth in a murine MM model, without host toxicity. In conclusion, these results indicate that CuB interferes with multiple cellular pathways in MM cells. CuB thus represents a promising therapeutic tool for the treatment of MM. PMID:27418139

  7. Activation of Blood CD3+CD56+CD8+ T Cells during Pregnancy and Multiple Sclerosis

    Science.gov (United States)

    de Andrés, Clara; Fernández-Paredes, Lidia; Tejera-Alhambra, Marta; Alonso, Bárbara; Ramos-Medina, Rocío; Sánchez-Ramón, Silvia

    2017-01-01

    A striking common feature of most autoimmune diseases is their female predominance, with at least twice as common among women than men in relapsing–remitting multiple sclerosis (MS), the prevailing MS clinical form with onset at childbearing age. This fact, together with the protective effect on disease activity during pregnancy, when there are many biological changes including high levels of estrogens and progesterone, puts sex hormones under the spotlight. The role of natural killer (NK) and NKT cells in MS disease beginning and course is still to be elucidated. The uterine NK (uNK) cells are the most predominant immune population in early pregnancy, and the number and function of uNK cells infiltrating the endometrium are sex-hormones’ dependent. However, there is controversy on the role of estrogen or progesterone on circulating NK (CD56dim and CD56bright) and NKT cells’ subsets. Here, we show a significantly increased activation of CD3+CD56+CD8+ cells in pregnant MS women (MSP) compared with non-pregnant MS women (NPMS) (p pregnancy. Further studies on specific CD8+ NKT cells function and their role in pregnancy beneficial effects on MS are warranted to move forward more effective MS treatments. PMID:28280497

  8. Multiple unit activity recorded longitudinally in rats from pubescence to old age.

    Science.gov (United States)

    Malmo, H P; Malmo, R B

    1982-01-01

    Longitudinal multiple unit activity (MUA) recordings of excellent quality over time periods as long as 26 months are described. The validity of the method was demonstrated by showing persistence of specific and idiosyncratic MUA responses to controlled sensory stimulation over these long time periods. This longitudinal MUA method was used to study level of localization neuronal activity as a function of aging. In agreement with deoxyglucose data from Sokoloff's laboratory, we found significant age-related declines in inferior and superior colliculi. In addition, our results showed the advantage of a longitudinal method over a cross-sectional one in following progressive changes into old age. The further declines in midbrain MUA level (though not in forebrain level) from middle age to old age that we observed were highly significant. The deoxyglucose method, on the other hand, had failed to show this kind of progression in those midbrain sites, probably because of a survival effect, a common sampling artifact in cross-sectional studies of aging.

  9. Augmented expression of urokinase plasminogen activator and extracellular matrix proteins associates with multiple myeloma progression.

    Science.gov (United States)

    Khan, Rehan; Gupta, Nidhi; Kumar, Raman; Sharma, Manoj; Kumar, Lalit; Sharma, Alpana

    2014-06-01

    Multiple myeloma (MM) represents a B cell malignancy, characterized by a monoclonal proliferation of malignant plasma cells. Interactions between tumor cells and extracellular matrix (ECM) are of importance for tumor invasion and metastasis. Protein levels of urokinase plasminogen activator (uPA) and fibulin 1, nidogen and laminin in plasma and serum respectively and mRNA levels of these molecules in peripheral blood mononuclear cells were determined in 80 subjects by using ELISA and quantitative PCR and data was analyzed with severity of disease. Pearson correlation was determined to observe interrelationship between different molecules. A statistical significant increase for ECM proteins (laminin, nidogen and fibulin 1) and uPA at circulatory level as well as at mRNA level was observed compared to healthy controls. The levels of these molecules in serum might be utilized as a marker of active disease. Significant positive correlation of all ECM proteins with uPA was found and data also correlates with severity of disease. Strong association found between ECM proteins and uPA in this study supports that there might be interplay between these molecules which can be targeted. This study on these molecules may help to gain insight into processes of growth, spread, and clinical behavior of MM.

  10. Predictability of Operant Behavior of Rats by Prefrontal Multiple Unit Activities

    Science.gov (United States)

    Fujiwara, Sei-Etsu; Akema, Tatsuo; Izaki, Yoshinori

    To investigate the possibility of a brain computer interface (BCI) constructed using activities of the prefrontal cortex (PFC), we analyzed PFC multiple unit activities (MUAs) during a delayed reinforcement (DRF) lever press task in rats. In the DRF task, each trial consisted of two lever press responses (R1, R2): R1 as the trial initiation, R2 as a pre-conditioned response to a stimulus (buzzer) for a reward. Between R1 and the buzzer, rats were required to inhibit the lever press (waiting phase). The trial was evaluated as incorrect if rats pressed the lever during the waiting phase. Results show that the mean firing rate (MFR) was significantly lower around the time of R1 compared with the pre-trial time in correct trials, although no significant changes were found in incorrect trials. From a neuroengineering perspective, the MFR of each single trial was calculated. Most correct trials showed decreasing MFR around the time of R1. The PFC MUA might be useful for BCI.

  11. QSAR modeling of antimalarial activity of urea derivatives using genetic algorithm–multiple linear regressions

    Directory of Open Access Journals (Sweden)

    Abolghasem Beheshti

    2016-05-01

    Full Text Available A quantitative structure–activity relationship (QSAR was performed to analyze antimalarial activities of 68 urea derivatives using multiple linear regressions (MLR. QSAR analyses were performed on the available 68 IC50 oral data based on theoretical molecular descriptors. A suitable set of molecular descriptors were calculated to represent the molecular structures of compounds, such as constitutional, topological, geometrical, electrostatic and quantum-chemical descriptors. The important descriptors were selected with the aid of the genetic algorithm (GA method. The obtained model was validated using leave-one-out (LOO cross-validation; external test set and Y-randomization test. The root mean square errors (RMSE of the training set, and the test set for GA–MLR model were calculated to be 0.314 and 0.486, the square of correlation coefficients (R2 were obtained 0.801 and 0.803, respectively. Results showed that the predictive ability of the model was satisfactory, and it can be used for designing similar group of antimalarial compounds.

  12. Online multiple intelligence teaching tools (On-MITT) for enhancing interpersonal teaching activities

    Science.gov (United States)

    Mohamad, Siti Nurul Mahfuzah; Salam, Sazilah; Bakar, Norasiken; Sui, Linda Khoo Mei

    2014-07-01

    The theories of Multiple Intelligence (MI) used in this paper apply to students with interpersonal intelligence who is encouraged to work together in cooperative groups where interpersonal interaction is practiced. In this context, students used their knowledge and skills to help the group or partner to complete the tasks given. Students can interact with each other as they learn and the process of learning requires their verbal and non-verbal communication skills, co-operation and empathy in the group. Meanwhile educators can incorporate cooperative learning in groups in the classroom. On-MITT provides various tools to facilitate lecturers in preparing e-content that applies interpersonal intelligence. With minimal knowledge of Information and Technology (IT) skills, educators can produce creative and interesting teaching activities and teaching materials. The objective of this paper is to develop On-MITT prototype for interpersonal teaching activities. This paper addressed initial prototype of this study. An evaluation of On-MITT has been completed by 20 lecturers of Malaysian Polytechnics. Motivation Survey Questionnaire is used as the instrument to measure four motivation variables: ease of use, enjoyment, usefulness and self-confidence. Based on the findings, the On-MITT can facilitate educators to prepare teaching materials that are compatible for interpersonal learner.

  13. Inverse correlation of expression of microRNA-140-5p with progression of multiple sclerosis and differentiation of encephalitogenic T helper type 1 cells.

    Science.gov (United States)

    Guan, Hongbing; Singh, Udai P; Rao, Roshni; Mrelashvili, Davit; Sen, Souvik; Hao, Haiping; Zumbrun, Elizabeth E; Singh, Narendra P; Nagarkatti, Prakash S; Nagarkatti, Mitzi

    2016-04-01

    The role of microRNA in the regulation of encephalitogenic T-cell development is of interest in understanding the pathogenesis of multiple sclerosis (MS). Direct binding of microRNAs to their target mRNAs usually suppresses gene expression and facilitates mRNA degradation. In this study, we observed that the expression of several microRNAs was significantly altered in patients with MS. Interestingly, the expression of miR-140-5p, among other microRNAs, was significantly decreased in the peripheral blood mononuclear cells of patients with MS, and this microRNA may regulate encephalitogenic T helper type 1 (Th1) cell differentiation. The expression level of miR-140-5p was inversely correlated with disease severity with greater reduction in relapsing disease compared with remitting disease. Transfection of synthetic miR-140-5p in peripheral blood mononuclear cells suppressed encephalitogenic Th1 differentiation. Signal transducer and activator of transcription 1 (STAT1) was the functional target of miR-140-5p - transfection of the synthetic miR-140-5p suppressed activation of STAT1 and the expression of its downstream target, T-bet. Our results suggested that miR-140-5p is probably involved in the regulation of encephalitogenic T cells in the pathogenesis of MS.

  14. Structural basis of specific inhibition of tissue-type plasminogen activator by plasminogen activators inhibitor-1

    Directory of Open Access Journals (Sweden)

    Lihu Gong

    2016-03-01

    Full Text Available Thrombosis is a leading cause of death worldwide [1]. Recombinant tissue-type plasminogen activator (tPA is the FDA-approved thrombolytic drug for ischemic strokes, myocardial infarction and pulmonary embolism. tPA is a multi-domain serine protease of the trypsin-family [2] and catalyses the critical step in fibrinolysis [3], converting the zymogen plasminogen to the active serine protease plasmin, which degrades the fibrin network of thrombi and blood clots. tPA is rapidly inactivated by endogenous plasminogen activators inhibitor-1 (PAI-1 [4] (Fig. 1. Engineering on tPA to reduce its inhibition by PAI-1 without compromising its thrombolytic effect is a continuous effort [5]. Tenecteplase (TNK-tPA is a newer generation of tPA variant showing slower inhibition by PAI-1 [6]. Extensive studies to understand the molecular interactions between tPA and PAI-1 have been carried out [7–18], however, the precise details at atomic resolution remain unknown. We report the crystal structure of tPA·PAI-1 complex here. The methods required to achieve these data include: (1 recombinant expression and purification of a PAI-1 variant (14-1B containing four mutations (N150H, K154T, Q319L, and M354I, and a tPA serine protease domain (tPA-SPD variant with three mutations (C122A, N173Q, and S195A, in the chymotrypsin numbering [19]; (2 formation of a tPA-SPD·PAI-1 Michaëlis complex in vitro [19]; and (3 solving the three-dimensional structure for this complex by X-ray crystallography [deposited in the PDB database as 5BRR]. The data explain the specificity of PAI-1 for tPA and uPA [19,20], and provide structural basis to design newer generation of PAI-1-resistant tPA variants as thrombolytic agents [19].

  15. Exploratory qualitative case study of lab-type activity interactions in an online graduate geoscience course

    Science.gov (United States)

    Ciavarella, Veronica C.

    This exploratory qualitative case study investigated the use of lab-type activities in an online graduate geoscience course. Constructivism is the theoretical framework used to explain how learning happens in lab-type activity, and provided the goals to which successful learning in lab-type activity is compared. This study focused on the learner-instructor, learner-learner, and perceptions of the learner-content interactions that occurred related to lab-type activities in an online graduate geoscience course to determine: if the instructor appeared as a facilitator of the learning process in the interactions over the activities; if students engaged in discussion and reflection about the activities; if students perceived the activities as meaningful and authentic; and if students perceived using higher order thinking and prior knowledge while interacting with the content. Ten graduate students from three offerings of the course participated in this study, as well as the instructor and designer of the course content and lab-type activities. Data were collected through interviews, and observation and analysis of the lab-type activities, instructor feedback to students in their graded activities, and discussion that occurred between the instructor and students and among students about the lab-type activities in discussion forums. The nature of the instructor's interactions in discussion forums, in feedback to students on graded activities, and reported by students' in interviews supported that, in the learner-instructor interactions, the instructor of this course was a facilitator who guided and scaffolded the students towards successfully completing the activities. Students engaged in discussion and reflected on the activities, but most learner-learner interactions in discussion forums about the lab-type activities appeared to occur for the purpose of comparison of results, support, and empathy. Students' success at higher order thinking type questions in lab-type

  16. Hormonal Regulation of Expression of Tissue Type Plasminogen Activator and Plasminogen Activator Inhibitor Type 1 in Cultured Rat Granulosa Cells

    Institute of Scientific and Technical Information of China (English)

    刘以训; 彭晓蓉; 刘奎

    1994-01-01

    In the present study, gonadotropin and gonadotropin-releasing hormone (GnRH) regulation of tPA and PAI-1 expression in PMSG-primed granulosa cells has been investigated, (i) Addition of go-nadotropins (FSH and LH) and GnRH agonist (GnRHa) or PMA to the culture increases tPA activity) FSH (or LH) plus GnRHa (or PMA) in the culture further enhances the enzyme production to such an extent that a more obvious effect than the additive effect caused by these hormones used alone has been observed; (ii) in contrast, FSH and LH decrease PAI-1 activity, whereas GnRHa and PMA alone markedly increase PAI-1 mRNA level and PAI-1 activity. Because FSH and LH stimulate tPA production and have no significant effect on PAI-1 mRNA induction, the observed inhibition of PAI-1 activity by gonadotropins may be due to the occurrence of neutralization of PA and PAI-1 proteins in the conditioned media by the formation of complexes between PA and PAI-1 ; (iii) increases in PAI-1 mRNA level and activity by GnRH and PMA are complet

  17. Effect of Celebrity Endorsement in Advertising Activities by Product Type

    Directory of Open Access Journals (Sweden)

    Karasiewicz Grzegorz

    2014-12-01

    Full Text Available This article seeks to answer two related questions: are celebrity endorsements more likely to be result in a higher evaluation of the product being advertised than use of an anonymous individual (e.g. a typical consumer; and, if present, do these positive effects vary by product category? To answer these two questions research was conducted on a 237 student sample employing a quasi-experiment consisting of four groups (two product categories and two types of endorsers using data collected through an online survey. The results indicate that celebrity endorsements do have a positive impact on the evaluation of durable goods, but do not affect the evaluation of frequently purchased products. This finding largely confirms the assumptions of the match-up model, the meaning transfer model, and the ELM model.

  18. Antiviral Activity of Hatay Propolis Against Replication of Herpes Simplex Virus Type 1 and Type 2.

    Science.gov (United States)

    Yildirim, Ayse; Duran, Gulay Gulbol; Duran, Nizami; Jenedi, Kemal; Bolgul, Behiye Sezgin; Miraloglu, Meral; Muz, Mustafa

    2016-02-09

    BACKGROUND Propolis is a bee product widely used in folk medicine and possessing many pharmacological properties. In this study we aimed to investigate: i) the antiviral activities of Hatay propolis samples against HSV-1 and HSV-2 in HEp-2 cell line, and ii) the presence of the synergistic effects of propolis with acyclovir against these viruses. MATERIAL AND METHODS All experiments were carried out in HEp-2 cell cultures. Proliferation assays were performed in 24-well flat bottom microplates. We inoculated 1x105 cells per ml and RPMI 1640 medium with 10% fetal calf serum into each well. Studies to determine cytotoxic effect were performed. To investigate the presence of antiviral activity of propolis samples, different concentrations of propolis (3200, 1600, 800, 400, 200, 100, 75, 50, and 25 μg/mL) were added into the culture medium. The amplifications of HSV-1 and HSV-2 DNA were performed by real-time PCR method. Acyclovir (Sigma, USA) was chosen as a positive control. Cell morphology was evaluated by scanning electron microscopy (SEM). RESULTS The replication of HSV-1 and HSV-2 was significantly suppressed in the presence of 25, 50, and 100 μg/mL of Hatay propolis. We found that propolis began to inhibit HSV-1 replication after 24 h of incubation and propolis activity against HSV-2 was found to start at 48 h following incubation. The activity of propolis against both HSV-1 and HSV-2 was confirmed by a significant decrease in the number of viral copies. CONCLUSIONS We determined that Hatay propolis samples have important antiviral effects compared with acyclovir. In particular, the synergy produced by antiviral activity of propolis and acyclovir combined had a stronger effect against HSV-1 and HSV-2 than acyclovir alone.

  19. Does breathing type influence electromyographic activity of obligatory and accessory respiratory muscles?

    Science.gov (United States)

    Gutiérrez, M F; Valenzuela, S; Miralles, R; Portus, C; Santander, H; Fuentes, A D; Celhay, I

    2014-11-01

    Craniomandibular electromyographic (EMG) studies frequently include several parameters, e.g. resting, chewing and tooth-clenching. EMG activity during these parameters has been recorded in the elevator muscles, but little is known about the respiratory muscles. The aim of this study was to compare EMG activity in obligatory and accessory respiratory muscles between subjects with different breathing types. Forty male subjects were classified according to their breathing type into two groups of 20 each: costo-diaphragmatic breathing type and upper costal breathing type. Bipolar surface electrodes were placed on the sternocleidomastoid, diaphragm, external intercostal and latissimus dorsi muscles. EMG activity was recorded during the following tasks: (i) normal quiet breathing, (ii) maximal voluntary clenching in intercuspal position, (iii) natural rate chewing until swallowing threshold, (iv) short-time chewing. Diaphragm EMG activity was significantly higher in the upper costal breathing type than in the costo-diaphragmatic breathing type in all tasks (P breathing type than in the costo-diaphragmatic breathing type in tasks 3 and 4 (P breathing types in the tasks studied (P > 0·05). The significantly higher EMG activity observed in subjects with upper costal breathing than in the costo-diaphragmatic breathing type suggests that there could be differences in motor unit recruitment strategies depending on the breathing type. This may be an expression of the adaptive capability of muscle chains in subjects who clinically have a different thoraco-abdominal expansion during inspiration at rest.

  20. Effectiveness of rehabilitation in multiple sclerosis relapse on fatigue, self-efficacy and physical activity.

    Science.gov (United States)

    Nedeljkovic, Una; Raspopovic, Emilija Dubljanin; Ilic, Nela; Vujadinovic, Sanja Tomanovic; Soldatovic, Ivan; Drulovic, Jelena

    2016-09-01

    Relapse of disease is one of the most prominent characteristics of multiple sclerosis. Effectiveness of rehabilitation programmes on fatigue, self-efficacy (SE) and physical activity (PA) has not been investigated so far in context of relapse. The aim of our study was to examine if rehabilitation programme in addition to high-dose methylprednisolone (HDMP) during relapse of disease can influence fatigue, SE and PA more than corticosteroid therapy alone. Patients were randomized in control group receiving only HDMP and experimental group which was in addition included in rehabilitation programme. Outcome measures used were Fatigue Severity Scale (FSS), Multiple Sclerosis Self- Efficacy scale (MSSES), Godin Leisure-Time Exercise Questionnaire (GLTEQ), completed on baseline, 1 and 3 months later. There was no significant change in FSS in both time points, despite different trend seen between groups. The mean MSSES for function and control improved significantly in treatment group after 1 month (807.1 ± 96.8, p = 0.005; 665.3 ± 145.1, p = 0.05) and 3 months (820 ± 83.5, p = 0.004; 720.0 ± 198.2, p = 0.016.) compared to baseline values. The mean GLTEQ score was significantly higher in the treatment group compared to the control at both follow-up time points (45.7 ± 7.6, p < 0.001; 34.3 ± 22.4, p < 0.01). Rehabilitation started along with corticosteroid treatment induced significant improvement in PA compared to HDMP therapy alone. It also influenced noticeable changes in self-efficacy, but effect on fatigue was insufficient.

  1. Characterization of human endothelial cell urokinase-type plasminogen activator receptor protein and messenger RNA

    DEFF Research Database (Denmark)

    Barnathan, E S; Kuo, A; Karikó, K

    1990-01-01

    Human umbilical vein endothelial cells in culture (HUVEC) express receptors for urokinase-type plasminogen activators (u-PA). The immunochemical nature of this receptor and its relationship to u-PA receptors expressed by other cell types is unknown. Cross-linking active site-blocked u-PA to HUVEC...

  2. Activation of the chicken type I IFN response by infectious bronchitis coronavirus

    NARCIS (Netherlands)

    Kint, J.; Fernandez Gutierrez, M.M.; Maier, H.J.; Britton, P.; Langereis, M.A.; Koumans, J.; Wiegertjes, G.F.; Forlenza, M.

    2015-01-01

    Coronaviruses from both the Alpha and Betacoronavirus genera, interfere with the type I interferon (IFN) response in various ways, ensuring limited activation of the IFN response in most cell types. Of Gammacoronaviruses that mainly infect birds, little is known about activation of the host immune r

  3. Effect of Different Types of Small-Group Activities on Students' Conversations

    Science.gov (United States)

    Young, Krista K.; Talanquer, Vicente

    2013-01-01

    Teaching reform efforts in chemistry education often involve engaging students in small-group activities of different types. This study focused on the analysis of how activity type affected the nature of group conversations. In particular, we analyzed the small-group conversations of students enrolled in a chemistry course for nonscience majors.…

  4. Linear Resonance Compressor for Stirling-Type Cryocoolers Activated by Piezoelectric Stack-Type Elements

    Science.gov (United States)

    Sobol, S.; Grossman, G.

    2015-12-01

    A novel type of a PZT- based compressor operating at mechanical resonance, suitable for pneumatically-driven Stirling-type cryocoolers was developed theoretically and built practically during this research. A resonance operation at relatively low frequency was achieved by incorporating the piezo ceramics into the moving part, and by reducing the effective piezo stiffness using hydraulic amplification. The detailed concept, analytical model and the test results of the preliminary prototype were reported earlier and presented at ICC17 [2]. A fine agreement between the simulations and experiments spurred development of the current actual compressor designed to drive a miniature Pulse Tube cryocooler, particularly our MTSa model, which operates at 103 Hz and requires an average PV power of 11 W, filling pressure of 40 Bar and a pressure ratio of 1.3. The paper concentrates on design aspects and optimization of the governing parameters. The small stroke to diameter ratio (about 1:10) allows for the use of a composite diaphragm instead of a clearance-seal piston. The motivation is to create an adequate separation between the working fluid and the buffer gas of the compressor, thus preventing possible contamination in the cryocooler. Providing efficiency and power density similar to those of conventional linear compressors, the piezo compressor may serve as a good alternative for cryogenic applications requiring extreme reliability and absence of magnetic field interference.

  5. Involvement of multiple elements in FXR-mediated transcriptional activation of FGF19.

    Science.gov (United States)

    Miyata, Masaaki; Hata, Tatsuya; Yamakawa, Hiroki; Kagawa, Tatehiro; Yoshinari, Kouichi; Yamazoe, Yasushi

    2012-10-01

    The intestinal endocrine hormone human fibroblast growth factor 19 (FGF19) is involved in the regulation of not only hepatic bile acid metabolism but also carbohydrate and lipid metabolism. In the present study, bile acid/farnesoid X receptor (FXR) responsiveness in the FGF19 promoter region was investigated by a reporter assay using the human colon carcinoma cell line LS174T. The assay revealed the presence of bile acid/FXR-responsive elements in the 5'-flanking region up to 8.8 kb of FGF19. Deletion analysis indicated that regions from -1866 to -1833, from -1427 to -1353, and from -75 to +262 were involved in FXR responsiveness. Four, four, and two consecutive half-sites of nuclear receptors were observed in the three regions, respectively. An electrophoretic mobility shift assay (EMSA) and chromatin immunoprecipitation (ChIP) assay revealed FXR/retinoid X receptor α (RXRα) heterodimer binding in these three regions. EMSA and reporter assays using mutated constructs indicated that the nuclear receptor IR1, ER2, and DR8 motifs in the 5'-flanking region were involved in FXR responsiveness of FGF19. Lithocholic acid (LCA) (10 μM), chenodeoxycholic acid (CDCA) (10 μM), or GW4064 (0.1 μM) treatment increased reporter activity in a construct including the three motifs under FXR-expressing conditions whereas LCA and not CDCA or GW4064 treatment increased the reporter activity under pregnane X receptor (PXR)-expressing conditions. These results suggest that FGF19 is transcriptionally activated through multiple FXR-responsive elements in the promoter region.

  6. Assessment of multiple hormone activities of a UV-filter (octocrylene) in zebrafish (Danio rerio).

    Science.gov (United States)

    Zhang, Qiuya Y; Ma, Xiaoyan Y; Wang, Xiaochang C; Ngo, Huu Hao

    2016-09-01

    In this study, zebrafish (Danio rerio) were exposed to a UV-filter-octocrylene (OCT) with elevated concentrations for 28 d. The total body accumulation of OCT in zebrafish was found to reach 2321.01 ("L" level), 31,234.80 ("M" level), and 70,593.38 ng g(-1) ("H" level) when the average OCT exposure concentration was controlled at 28.61, 505.62, and 1248.70 μg L(-1), respectively. Gross and histological observations as well as RT-qPCR analysis were conducted to determine the effects of OCT accumulation on zebrafish. After exposure, the gonad-somatic index and percentage of vitellogenic oocytes were found to increase significantly in the ovaries of female zebrafish at the H accumulation level. Significant up-regulation of esr1 and cyp19b were observed in the gonads, as well as vtg1 in the livers for both female and male zebrafish. At M and H accumulation levels, apparent down-regulation of ar was observed in the ovaries and testis of the female and male zebrafish, respectively. Although the extent of the effects on zebrafish differed at different accumulation levels, the induction of vtg1 and histological changes in the ovaries are indications of estrogenic activity and the inhibition of esr1 and ar showed antiestrogenic and antiandrogenic activity, respectively. Thus, as OCT could easily accumulate in aquatic life such as zebrafish, one of its most of concern hazards would be the disturbance of the histological development and its multiple hormonal activities.

  7. Identification of Mars gully activity types associated with ice composition

    CERN Document Server

    Vincendon, Mathieu

    2015-01-01

    The detection of geologically recent channels at the end of the twentieth century rapidly suggested that liquid water could have been present on Mars up to recent times. A mechanism involving melting of water ice during ice ages in the last several million years progressively emerged during years following the first observations of these gullies. However, the recent discovery of current activity within gullies now suggests a paradigm shift where a contemporary CO2 ice-based and liquid water-free mechanism may form all gullies. Here we perform a survey of near-infrared observations and construct time sequences of water and CO2 ice formation and sublimation at active gully sites. We observe that all major new erosive features such as channel development or lengthening systematically occur where and, if applicable, when CO2 ice is observed or probable. CO2 ice layers are however estimated to be only 1 mm to 1 cm thick for low-latitude sites, which may have implication for potential formation mechanisms. We also ...

  8. Antiviral Activity of Hatay Propolis Against Replication of Herpes Simplex Virus Type 1 and Type 2

    OpenAIRE

    Yildirim, Ayse; Duran, Gulay Gulbol; DURAN, Nizami; Jenedi, Kemal; Bolgul, Behiye Sezgin; Miraloglu, Meral; MUZ, Mustafa

    2016-01-01

    Background Propolis is a bee product widely used in folk medicine and possessing many pharmacological properties. In this study we aimed to investigate: i) the antiviral activities of Hatay propolis samples against HSV-1 and HSV-2 in HEp-2 cell line, and ii) the presence of the synergistic effects of propolis with acyclovir against these viruses. Material/Methods All experiments were carried out in HEp-2 cell cultures. Proliferation assays were performed in 24-well flat bottom microplates. We...

  9. Multiple I-Type Lysozymes in the Hydrothermal Vent Mussel Bathymodiolus azoricus and Their Role in Symbiotic Plasticity.

    Directory of Open Access Journals (Sweden)

    Camille Detree

    Full Text Available The aim of this study was first to identify lysozymes paralogs in the deep sea mussel Bathymodiolus azoricus then to measure their relative expression or activity in different tissue or conditions. B. azoricus is a bivalve that lives close to hydrothermal chimney in the Mid-Atlantic Ridge (MAR. They harbour in specialized gill cells two types of endosymbiont (gram-bacteria: sulphide oxidizing bacteria (SOX and methanotrophic bacteria (MOX. This association is thought to be ruled by specific mechanism or actors of regulation to deal with the presence of symbiont but these mechanisms are still poorly understood. Here, we focused on the implication of lysozyme, a bactericidal enzyme, in this endosymbiosis. The relative expression of Ba-lysozymes paralogs and the global anti-microbial activity, were measured in natural population (Lucky Strike--1700 m, Mid-Atlantic Ridge, and in in situ experimental conditions. B. azoricus individuals were moved away from the hydrothermal fluid to induce a loss of symbiont. Then after 6 days some mussels were brought back to the mussel bed to induce a re-acquisition of symbiotic bacteria. Results show the presence of 6 paralogs in B. azoricus. In absence of symbionts, 3 paralogs are up-regulated while others are not differentially expressed. Moreover the global activity of lysozyme is increasing with the loss of symbiont. All together these results suggest that lysozyme may play a crucial role in symbiont regulation.

  10. A Survey of the High Order Multiplicity of Nearby Solar-type Binary Stars with Robo-AO

    Science.gov (United States)

    Riddle, Reed L.; Tokovinin, Andrei; Mason, Brian D.; Hartkopf, William I.; Roberts, Lewis C., Jr.; Baranec, Christoph; Law, Nicholas M.; Bui, Khanh; Burse, Mahesh P.; Das, H. K.; Dekany, Richard G.; Kulkarni, Shrinivas; Punnadi, Sujit; Ramaprakash, A. N.; Tendulkar, Shriharsh P.

    2015-01-01

    We conducted a survey of nearby binary systems composed of main sequence stars of spectral types F and G in order to improve our understanding of the hierarchical nature of multiple star systems. Using Robo-AO, the first robotic adaptive optics instrument, we collected high angular resolution images with deep and well-defined detection limits in the Sloan Digital Sky Survey i' band. A total of 695 components belonging to 595 systems were observed. We prioritized observations of faint secondary components with separations over 10'' to quantify the still poorly constrained frequency of their subsystems. Of the 214 secondaries observed, 39 contain such subsystems; 19 of those were discovered with Robo-AO. The selection-corrected frequency of secondary subsystems with periods from 103.5 to 105 days is 0.12 ± 0.03, the same as the frequency of such companions to the primary. Half of the secondary pairs belong to quadruple systems where the primary is also a close pair, showing that the presence of subsystems in both components of the outer binary is correlated. The relatively large abundance of 2+2 quadruple systems is a new finding, and will require more exploration of the formation mechanism of multiple star systems. We also targeted close binaries with periods less than 100 yr, searching for their distant tertiary components, and discovered 17 certain and 2 potential new triples. In a subsample of 241 close binaries, 71 have additional outer companions. The overall frequency of tertiary components is not enhanced, compared to all (non-binary) targets, but in the range of outer periods from 106 to 107.5 days (separations on the order of 500 AU), the frequency of tertiary components is 0.16 ± 0.03, exceeding the frequency of similar systems among all targets (0.09) by almost a factor of two. Measurements of binary stars with Robo-AO allowed us to compute first orbits for 9 pairs and to improve orbits of another 11 pairs.

  11. A SURVEY OF THE HIGH ORDER MULTIPLICITY OF NEARBY SOLAR-TYPE BINARY STARS WITH Robo-AO

    Energy Technology Data Exchange (ETDEWEB)

    Riddle, Reed L.; Bui, Khanh; Dekany, Richard G.; Kulkarni, Shrinivas; Tendulkar, Shriharsh P. [Division of Physics, Mathematics, and Astronomy, California Institute of Technology, Pasadena, CA 91125 (United States); Tokovinin, Andrei [Cerro Tololo Inter-American Observatory, Casilla 603, La Serena (Chile); Mason, Brian D.; Hartkopf, William I. [U.S. Naval Observatory, 3450 Massachusetts Avenue, Washington, DC 20392-5420 (United States); Roberts, Lewis C. Jr. [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Drive, Pasadena, CA 91109 (United States); Baranec, Christoph [Institute for Astronomy, University of Hawai" i at Mānoa, Hilo, HI 96720-2700 (United States); Law, Nicholas M. [Department of Physics and Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3255 (United States); Burse, Mahesh P.; Das, H. K.; Punnadi, Sujit; Ramaprakash, A. N. [Inter-University Centre for Astronomy and Astrophysics, Ganeshkhind, Pune, 411007 (India)

    2015-01-20

    We conducted a survey of nearby binary systems composed of main sequence stars of spectral types F and G in order to improve our understanding of the hierarchical nature of multiple star systems. Using Robo-AO, the first robotic adaptive optics instrument, we collected high angular resolution images with deep and well-defined detection limits in the Sloan Digital Sky Survey i' band. A total of 695 components belonging to 595 systems were observed. We prioritized observations of faint secondary components with separations over 10'' to quantify the still poorly constrained frequency of their subsystems. Of the 214 secondaries observed, 39 contain such subsystems; 19 of those were discovered with Robo-AO. The selection-corrected frequency of secondary subsystems with periods from 10{sup 3.5} to 10{sup 5} days is 0.12 ± 0.03, the same as the frequency of such companions to the primary. Half of the secondary pairs belong to quadruple systems where the primary is also a close pair, showing that the presence of subsystems in both components of the outer binary is correlated. The relatively large abundance of 2+2 quadruple systems is a new finding, and will require more exploration of the formation mechanism of multiple star systems. We also targeted close binaries with periods less than 100 yr, searching for their distant tertiary components, and discovered 17 certain and 2 potential new triples. In a subsample of 241 close binaries, 71 have additional outer companions. The overall frequency of tertiary components is not enhanced, compared to all (non-binary) targets, but in the range of outer periods from 10{sup 6} to 10{sup 7.5} days (separations on the order of 500 AU), the frequency of tertiary components is 0.16 ± 0.03, exceeding the frequency of similar systems among all targets (0.09) by almost a factor of two. Measurements of binary stars with Robo-AO allowed us to compute first orbits for 9 pairs and to improve orbits of another 11 pairs.

  12. Type IV secretion-dependent activation of host MAP kinases induces an increased proinflammatory cytokine response to Legionella pneumophila.

    Directory of Open Access Journals (Sweden)

    Sunny Shin

    2008-11-01

    Full Text Available The immune system must discriminate between pathogenic and nonpathogenic microbes in order to initiate an appropriate response. Toll-like receptors (TLRs detect microbial components common to both pathogenic and nonpathogenic bacteria, whereas Nod-like receptors (NLRs sense microbial components introduced into the host cytosol by the specialized secretion systems or pore-forming toxins of bacterial pathogens. The host signaling pathways that respond to bacterial secretion systems remain poorly understood. Infection with the pathogen Legionella pneumophila, which utilizes a type IV secretion system (T4SS, induced an increased proinflammatory cytokine response compared to avirulent bacteria in which the T4SS was inactivated. This enhanced response involved NF-kappaB activation by TLR signaling as well as Nod1 and Nod2 detection of type IV secretion. Furthermore, a TLR- and RIP2-independent pathway leading to p38 and SAPK/JNK MAPK activation was found to play an equally important role in the host response to virulent L. pneumophila. Activation of this MAPK pathway was T4SS-dependent and coordinated with TLR signaling to mount a robust proinflammatory cytokine response to virulent L. pneumophila. These findings define a previously uncharacterized host response to bacterial type IV secretion that activates MAPK signaling and demonstrate that coincident detection of multiple bacterial components enables immune discrimination between virulent and avirulent bacteria.

  13. Research activity with different types of scintillation materials

    Science.gov (United States)

    Brinkmann, K.-T.; Borisevich, A.; Diehl, S.; Dormenev, V.; Houzvicka, J.; Korjik, M.; Novotny, R. W.; Zaunick, H.-G.; Zimmermann, S.

    2016-10-01

    Nowadays there is a growing interest and demand in the development of new types of scintillation materials for experimental high energy physics. Future detector developments will focus on cheap, fast, and radiation hard materials, especially for application in collider experiments. The most recent results obtained by the Giessen group in close cooperation with colleagues from different institutes will be presented. The new start of the mass production of high quality lead tungstate crystals (PbWO4, PWO) for electromagnetic calorimetry was started by the company CRYTUR (Turnov, Czech Republic). We will present a detailed progress report on the research program of lead tungstate performed in the last two years. The latest results in the development of LuAG:Ce, YAG:Ce and LYSO:Ce inorganic fibers, grown by the micro pulling down method and cut with the heated wire technique as well as new glass ceramics material BaO*2SiO2 (DSB) doped by Ce and Gd will be presented. In addition, different samples of the organic plastic scintillator EJ-260 produced by the company Eljen Technology (Sweetwater, USA) have been characterized. The study has focused on the change of performance after irradiation with 150 MeV protons up to an integral fluence of 5-1013 protons/cm2 as well as with a strong 60Co gamma-source accumulating an integral dose of 100 Gy.

  14. Cell type-specific neuroprotective activity of untranslocated prion protein.

    Directory of Open Access Journals (Sweden)

    Elena Restelli

    Full Text Available BACKGROUND: A key pathogenic role in prion diseases was proposed for a cytosolic form of the prion protein (PrP. However, it is not clear how cytosolic PrP localization influences neuronal viability, with either cytotoxic or anti-apoptotic effects reported in different studies. The cellular mechanism by which PrP is delivered to the cytosol of neurons is also debated, and either retrograde transport from the endoplasmic reticulum or inefficient translocation during biosynthesis has been proposed. We investigated cytosolic PrP biogenesis and effect on cell viability in primary neuronal cultures from different mouse brain regions. PRINCIPAL FINDINGS: Mild proteasome inhibition induced accumulation of an untranslocated form of cytosolic PrP in cortical and hippocampal cells, but not in cerebellar granules. A cyclopeptolide that interferes with the correct insertion of the PrP signal sequence into the translocon increased the amount of untranslocated PrP in cortical and hippocampal cells, and induced its synthesis in cerebellar neurons. Untranslocated PrP boosted the resistance of cortical and hippocampal neurons to apoptotic insults but had no effect on cerebellar cells. SIGNIFICANCE: These results indicate cell type-dependent differences in the efficiency of PrP translocation, and argue that cytosolic PrP targeting might serve a physiological neuroprotective function.

  15. Identification of a novel multiple kinase inhibitor with potent antiviral activity against influenza virus by reducing viral polymerase activity

    Energy Technology Data Exchange (ETDEWEB)

    Sasaki, Yutaka; Kakisaka, Michinori; Chutiwitoonchai, Nopporn [Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan); Tajima, Shigeru [Department of Virology I, National Institute of Infectious Diseases, 1-23-1 Toyama, Shinjuku, Tokyo 162-8640 (Japan); Hikono, Hirokazu; Saito, Takehiko [Influenza and Prion Disease Research Center, National Institute of Animal Health, National Agriculture and Food Research Organization (NARO), 3-1-5 Kannondai, Tsukuba, Ibaraki 305-0856 (Japan); Aida, Yoko, E-mail: aida@riken.jp [Viral Infectious Diseases Unit, RIKEN, 2-1 Hirosawa, Wako, Saitama 351-0198 (Japan)

    2014-07-18

    Highlights: • Screening of 50,000 compounds and subsequent lead optimization identified WV970. • WV970 has antiviral effects against influenza A, B and highly pathogenic viral strains. • WV970 inhibits viral genome replication and transcription. • A target database search suggests that WV970 may bind to a number of kinases. • KINOMEscan screening revealed that WV970 has inhibitory effects on 15 kinases. - Abstract: Neuraminidase inhibitors are the only currently available influenza treatment, although resistant viruses to these drugs have already been reported. Thus, new antiviral drugs with novel mechanisms of action are urgently required. In this study, we identified a novel antiviral compound, WV970, through cell-based screening of a 50,000 compound library and subsequent lead optimization. This compound exhibited potent antiviral activity with nanomolar IC{sub 50} values against both influenza A and B viruses but not non-influenza RNA viruses. Time-of-addition and indirect immunofluorescence assays indicated that WV970 acted at an early stage of the influenza life cycle, but likely after nuclear entry of viral ribonucleoprotein (vRNP). Further analyses of viral RNA expression and viral polymerase activity indicated that WV970 inhibited vRNP-mediated viral genome replication and transcription. Finally, structure-based virtual screening and comprehensive human kinome screening were used to demonstrate that WV970 acts as a multiple kinase inhibitor, many of which are associated with influenza virus replication. Collectively, these results strongly suggest that WV970 is a promising anti-influenza drug candidate and that several kinases associated with viral replication are promising drug targets.

  16. Transcriptional Profiling of Vibrio parahaemolyticus exsA reveals a complex activation network for type III secretion

    Directory of Open Access Journals (Sweden)

    Aaron C. Liu

    2015-10-01

    Full Text Available Vibrio parahaemolyticus (Vp is a marine halophilic bacterium that is commonly associated with oysters and shrimp. Human consumption of contaminated shellfish can result in Vp mediated gastroenteritis and severe diarrheal disease. Vp encodes two type 3 secretion systems (T3SS-I and T3SS-II that have been functionally implicated in cytotoxicity and enterotoxicity respectively. In this study, we profiled protein secretion and temporal promoter activities associated with exsA and exsB gene expression. exsA is an AraC-like transcriptional activator that is critical for activating multiple operons that encode T3SS-1 genes, whereas exsB is thought to encode an outer membrane pilotin component for T3SS-1. The exsBA genetic locus has two predicted promoter elements. The predicted exsB and exsA promoters were individually cloned upstream of luxCDABE genes in reporter plasmid constructs allowing for in situ, real-time quantitative light emission measurements under many growth conditions. Low calcium growth conditions supported maximal exsB and exsA promoter activation. exsB promoter activity exhibited high basal activity and resulted in an exsBA co-transcript. Furthermore, a separate proximal exsA promoter showed initial low basal activity yet eventually exceeded that of exsB and reached maximal levels after 2.5 hours corresponding to an entry into early log phase. exsA promoter activity was significantly higher at 30oC than 37oC, which also coincided with increased secretion levels of specific T3SS-1 effector proteins. Lastly, bioinformatic analyses identified a putative expanded ExsA binding motif for multiple transcriptional operons. These findings suggest a two wave model of Vp T3SS-I induction that integrates two distinct promoter elements and environmental signals into a complex ExsA activation framework.

  17. Photometric properties for selected Algol-type binaries. VII. V404 and with magnetic activity

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Li-Yun; Pi, Qing-Feng; Zhu, Zhongzhong [College of Science/Department of Physics and NAOC-GZU Center for Astronomy, Guizhou University, Guiyang 550025 (China); Yang, Yuan-Gui, E-mail: liy_zhang@hotmail.com [School of Physics and Electronic Information, Huaibei Normal University, Huaibei 235000 Anhui Province (China)

    2014-03-01

    We present new CCD light curves of the short-period Algol-type eclipsing binary V404 And obtained in 2009-2011. The time-resolving multiple BVRI color light curves of the year 2011 with full phase coverage were analyzed simultaneously using the latest Wilson-Devinney program. We concluded that the configuration of two starspots on the primary is the most reliable explanation for the light curve distortions observed in 2011. Based on the new photometric solution, we further applied the spot model to explain the other light curves, including the previously published R-band light curves. We revealed that the starspots changed on a long timescale in terms of the spot parameters and the differences between Max. I and Max. II. Moreover, the O – C diagram spanning about 15 yr shows an upward parabola, which indicates a secular increase in the orbital period of V404 And. The orbital period increases at a rate of dP/dt = 5.3(0.3) × 10{sup –7} days yr{sup –1}, which might be interpreted by the angular momentum exchange via magnetic activity.

  18. Tel omerase Activity in Condyloma Acuminatum Tissue with Different HPV Types

    Institute of Scientific and Technical Information of China (English)

    涂亚庭; 陈善娟; 樊超; 林能兴; 刘厚君; 刘志香

    2002-01-01

    Summary: The telomerse activity in condyloma acuminatum (CA) tissue with human papillomavirus (HPV) types of 6/11 and 16/18 was detected to investigate the function of telomerase in the occur rence, development and carcinogenesis of genital CA. Forty-two biopsies from patients with gennital CA and 30 control tissue samples were tested for telomerase activity, HPV presence and types. The telomerase activity was determined by modified telomerase repeat amplification protocol (TRAP) as say and HPV typing by polymerase chain reaction (PCR) with typing-specific primers. Results showed that HPV-DNA was negative and the expression rate of telomerase was 16.7 % in all normal skin samples. All CA samples were positive for HPV (6/11 type was found in 32 cases, 16/18 in 3 and mixed type in 7). Telomerarase activity was detectable in all CA patients. The telomerase activity in CA of 16/18 type was apparently higher than in CA of 6/11 type. It was concluded that the hy-perplasia in CA might be increased as a result of HPV infection, suggesting that the activation of telomerase by HPV, especially by 16/18 type may play a role in the etiology and carcinogenesis of genital CA.

  19. Multiple GCD genes required for repression of GCN4, a transcriptional activator of amino acid biosynthetic genes in Saccharomyces cerevisiae.

    Science.gov (United States)

    Harashima, S; Hinnebusch, A G

    1986-11-01

    GCN4 encodes a positive regulator of multiple unlinked genes encoding amino acid biosynthetic enzymes in Saccharomyces cerevisiae. Expression of GCN4 is coupled to amino acid availability by a control mechanism involving GCD1 as a negative effector and GCN1, GCN2, and GCN3 as positive effectors of GCN4 expression. We used reversion of a gcn2 gcn3 double mutation to isolate new alleles of GCD1 and mutations in four additional GCD genes which we designate GCD10, GCD11, GCD12, and GCD13. All of the mutations lead to constitutive derepression of HIS4 transcription in the absence of the GCN2+ and GCN3+ alleles. By contrast, the gcd mutations require the wild-type GCN4 allele for their derepressing effect, suggesting that each acts by influencing the level of GCN4 activity in the cell. Consistent with this interpretation, mutations in each GCD gene lead to constitutive derepression of a GCN4::lacZ gene fusion. Thus, at least five gene products are required to maintain the normal repressed level of GCN4 expression in nonstarvation conditions. Interestingly, the gcd mutations are pleiotropic and also affect growth rate in nonstarvation conditions. In addition, certain alleles lead to a loss of M double-stranded RNA required for the killer phenotype. This pleiotropy suggests that the GCD gene products contribute to an essential cellular function, in addition to, or in conjunction with, their role in GCN4 regulation.

  20. Identification of Flap Motion Parameters for Vibration Reduction in Helicopter Rotors with Multiple Active Trailing Edge Flaps

    Directory of Open Access Journals (Sweden)

    Uğbreve;ur Dalli

    2011-01-01

    Full Text Available An active control method utilizing the multiple trailing edge flap configuration for rotorcraft vibration suppression and blade loads control is presented. A comprehensive model for rotor blade with active trailing edge flaps is used to calculate the vibration characteristics, natural frequencies and mode shapes of any complex composite helicopter rotor blade. A computer program is developed to calculate the system response, rotor blade root forces and moments under aerodynamic forcing conditions. Rotor blade system response is calculated using the proposed solution method and the developed program depending on any structural and aerodynamic properties of rotor blades, structural properties of trailing edge flaps and properties of trailing edge flap actuator inputs. Rotor blade loads are determined first on a nominal rotor blade without multiple active trailing edge flaps and then the effects of the active flap motions on the existing rotor blade loads are investigated. Multiple active trailing edge flaps are controlled by using open loop controllers to identify the effects of the actuator signal output properties such as frequency, amplitude and phase on the system response. Effects of using multiple trailing edge flaps on controlling rotor blade vibrations are investigated and some design criteria are determined for the design of trailing edge flap controller that will provide actuator signal outputs to minimize the rotor blade root loads. It is calculated that using the developed active trailing edge rotor blade model, helicopter rotor blade vibrations can be reduced up to 36% of the nominal rotor blade vibrations.

  1. New Biocatalyst with Multiple Enzymatic Activities for Treatment of Complex Food Wastewaters

    Directory of Open Access Journals (Sweden)

    Olga Senko

    2008-01-01

    Full Text Available The cells of filamentous fungus R. oryzae entrapped in the polyvinyl alcohol cryogelare capable of producing various extracellular hydrolytic enzymes (proteases, amylases, lipases and are used for the treatment of complex wastewaters of food industry. Five types of media simulating the wastewater of various food enterprises were treated under batch conditions for 600 h. Fats containing mostly residues of unsaturated fatty acids, as well as casein, glucose, sucrose, starch, soybean flour and various salts were the main components of the treated wastewaters. The immobilized cells concurrently possessed lipolytic, amylolytic and proteolytic activities. The level of each enzymatic activity depended on the wastewater content. The physiological state of immobilized cells was monitored by bioluminescent method. The intracellular adenosine triphosphate (ATP concentration determined in the granules with immobilized cells was high enough and almost constant for all the period of biocatalyst application confirming thereby the active metabolic state of the cells. The study of mechanical strength of biocatalyst granules allowed revealing the differences in the values of modulus of biocatalyst elasticity at the beginning and at the end of its use for the wastewater treatment. The decrease in chemical oxygen demand of the tested media after their processing by immobilized biocatalyst was 68–79 % for one working cycle.

  2. The Legionella pneumophila IcmSW complex interacts with multiple Dot/Icm effectors to facilitate type IV translocation.

    Directory of Open Access Journals (Sweden)

    Eric D Cambronne

    2007-12-01

    Full Text Available Many gram-negative pathogens use a type IV secretion system (T4SS to deliver effector proteins into eukaryotic host cells. The fidelity of protein translocation depends on the efficient recognition of effector proteins by the T4SS. Legionella pneumophila delivers a large number of effector proteins into eukaryotic cells using the Dot/Icm T4SS. How the Dot/Icm system is able to recognize and control the delivery of effectors is poorly understood. Recent studies suggest that the IcmS and IcmW proteins interact to form a stable complex that facilitates translocation of effector proteins by the Dot/Icm system by an unknown mechanism. Here we demonstrate that the IcmSW complex is necessary for the productive translocation of multiple Dot/Icm effector proteins. Effector proteins that were able to bind IcmSW in vitro required icmS and icmW for efficient translocation into eukaryotic cells during L. pneumophila infection. We identified regions in the effector protein SidG involved in icmSW-dependent translocation. Although the full-length SidG protein was translocated by an icmSW-dependent mechanism, deletion of amino terminal regions in the SidG protein resulted in icmSW-independent translocation, indicating that the IcmSW complex is not contributing directly to recognition of effector proteins by the Dot/Icm system. Biochemical and genetic studies showed that the IcmSW complex interacts with a central region of the SidG protein. The IcmSW interaction resulted in a conformational change in the SidG protein as determined by differences in protease sensitivity in vitro. These data suggest that IcmSW binding to effectors could enhance effector protein delivery by mediating a conformational change that facilitates T4SS recognition of a translocation domain located in the carboxyl region of the effector protein.

  3. Metformin Effect on Nontargeted Metabolite Profiles in Patients With Type 2 Diabetes and in Multiple Murine Tissues.

    Science.gov (United States)

    Adam, Jonathan; Brandmaier, Stefan; Leonhardt, Jörn; Scheerer, Markus F; Mohney, Robert P; Xu, Tao; Bi, Jie; Rotter, Markus; Troll, Martina; Chi, Shen; Heier, Margit; Herder, Christian; Rathmann, Wolfgang; Giani, Guido; Adamski, Jerzy; Illig, Thomas; Strauch, Konstantin; Li, Yixue; Gieger, Christian; Peters, Annette; Suhre, Karsten; Ankerst, Donna; Meitinger, Thomas; Hrabĕ de Angelis, Martin; Roden, Michael; Neschen, Susanne; Kastenmüller, Gabi; Wang-Sattler, Rui

    2016-12-01

    Metformin is the first-line oral medication to increase insulin sensitivity in patients with type 2 diabetes (T2D). Our aim was to investigate the pleiotropic effect of metformin using a nontargeted metabolomics approach. We analyzed 353 metabolites in fasting serum samples of the population-based human KORA (Cooperative Health Research in the Region of Augsburg) follow-up survey 4 cohort. To compare T2D patients treated with metformin (mt-T2D, n = 74) and those without antidiabetes medication (ndt-T2D, n = 115), we used multivariable linear regression models in a cross-sectional study. We applied a generalized estimating equation to confirm the initial findings in longitudinal samples of 683 KORA participants. In a translational approach, we used murine plasma, liver, skeletal muscle, and epididymal adipose tissue samples from metformin-treated db/db mice to further corroborate our findings from the human study. We identified two metabolites significantly (P < 1.42E-04) associated with metformin treatment. Citrulline showed lower relative concentrations and an unknown metabolite X-21365 showed higher relative concentrations in human serum when comparing mt-T2D with ndt-T2D. Citrulline was confirmed to be significantly (P < 2.96E-04) decreased at 7-year follow-up in patients who started metformin treatment. In mice, we validated significantly (P < 4.52E-07) lower citrulline values in plasma, skeletal muscle, and adipose tissue of metformin-treated animals but not in their liver. The lowered values of citrulline we observed by using a nontargeted approach most likely resulted from the pleiotropic effect of metformin on the interlocked urea and nitric oxide cycle. The translational data derived from multiple murine tissues corroborated and complemented the findings from the human cohort.

  4. Structural basis of specific inhibition of tissue-type plasminogen activator by plasminogen activators inhibitor-1

    Science.gov (United States)

    Gong, Lihu; Liu, Min; Zeng, Tu; Shi, Xiaoli; Yuan, Cai; Andreasen, Peter A.; Huang, Mingdong

    2016-01-01

    Thrombosis is a leading cause of death worldwide [1]. Recombinant tissue-type plasminogen activator (tPA) is the FDA-approved thrombolytic drug for ischemic strokes, myocardial infarction and pulmonary embolism. tPA is a multi-domain serine protease of the trypsin-family [2] and catalyses the critical step in fibrinolysis [3], converting the zymogen plasminogen to the active serine protease plasmin, which degrades the fibrin network of thrombi and blood clots. tPA is rapidly inactivated by endogenous plasminogen activators inhibitor-1 (PAI-1) [4] (Fig. 1). Engineering on tPA to reduce its inhibition by PAI-1 without compromising its thrombolytic effect is a continuous effort [5]. Tenecteplase (TNK-tPA) is a newer generation of tPA variant showing slower inhibition by PAI-1 [6]. Extensive studies to understand the molecular interactions between tPA and PAI-1 have been carried out [7], [8], [9], [10], [11], [12], [13], [14], [15], [16], [17], [18], however, the precise details at atomic resolution remain unknown. We report the crystal structure of tPA·PAI-1 complex here. The methods required to achieve these data include: (1) recombinant expression and purification of a PAI-1 variant (14-1B) containing four mutations (N150H, K154T, Q319L, and M354I), and a tPA serine protease domain (tPA-SPD) variant with three mutations (C122A, N173Q, and S195A, in the chymotrypsin numbering) [19]; (2) formation of a tPA-SPD·PAI-1 Michaëlis complex in vitro [19]; and (3) solving the three-dimensional structure for this complex by X-ray crystallography [deposited in the PDB database as 5BRR]. The data explain the specificity of PAI-1 for tPA and uPA [19], [20], and provide structural basis to design newer generation of PAI-1-resistant tPA variants as thrombolytic agents [19]. PMID:26909366

  5. Development and comparison of a generic multiple-locus variable-number tandem repeat analysis with PFGE for typing of Salmonella entericasubsp. enterica

    DEFF Research Database (Denmark)

    Kjeldsen, Marianne Kirstine; Torpdahl, Mia; Pedersen, Karl

    2015-01-01

    Aims Salmonella enterica subsp. enterica causes salmonellosis in humans and animals. Serovar specific multiple-locus variable-number tandem repeat analysis (MLVA) is widely used for Salmonella surveillance; however, isolates have to be serotyped prior to MLVA typing and only the most common serov...... inexpensive and fast surveillance for laboratories without resources for both serotyping and molecular typing, e.g. PFGE or sequence-based methods, and thereby improve the effectiveness of epidemiological investigations of Salmonella infections globally....

  6. Efficient HOMO-LUMO separation by multiple resonance effect toward ultrapure blue thermally activated delayed fluorescence

    Science.gov (United States)

    Hatakeyama, Takuji; Ikuta, Toshiaki; Shiren, Kazushi; Nakajima, Kiichi; Nomura, Shintaro; Ni, Jingping

    2016-09-01

    Organic light-emitting diodes (OLEDs) play an important role in the new generation of flat-panel displays. Conventional OLEDs employing fluorescent materials together with triplet-triplet annihilation suffer from a relatively low internal quantum efficiency (IQE) of 62.5%. On the other hand, the IQE of OLEDs employing phosphorescent or thermally activated delayed fluorescence (TADF) materials can reach 100%. However, these materials exhibit very broad peaks with a full-width at half-maximum (FWHM) of 70-100 nm and cannot satisfy the color-purity requirements for displays. Therefore, the latest commercial OLED displays employ blue fluorescent materials with a relatively low IQE, and efficient blue emitters with a small FWHM are highly needed. In our manuscript, we present organic molecules that exhibit ultrapure blue fluorescence based on TADF. These molecules consist of three benzene rings connected by one boron and two nitrogen atoms, which establish a rigid polycyclic framework and significant localization of the highest occupied and lowest unoccupied molecular orbitals by a multiple resonance effect. An OLED device based on the new emitter exhibits ultrapure blue emission at 467 nm with an FWHM of 28 nm, Commission Internationale de l'Eclairage (CIE) coordinates of (0.12, 0.13), and an IQE of 100%, which represent record-setting performance for blue OLED devices.

  7. Disease Activity and Conversion into Multiple Sclerosis after Optic Neuritis Is Treated with Erythropoietin

    Directory of Open Access Journals (Sweden)

    Kurt-Wolfram Sühs

    2016-09-01

    Full Text Available Changes in cerebral lesion load by magnetic resonance imaging (MRI in patients from a double-blind, placebo-controlled, phase II study on erythropoietin in clinically isolated optic neuritis (ClinicalTrials.gov, NCT00355095 were analyzed. Therefore, patients with acute optic neuritis were assigned to receive either 33,000 IU of recombinant human erythropoietin (IV daily for three days, or a placebo, as an add-on to methylprednisolone. Of 35 patients, we investigated changes in cerebral lesion load in MRIs obtained at baseline and at weeks 4, 8, and 16. In 5 of the 35 patients, we found conversion into multiple sclerosis (MS based on MRI progression only. These five patients had received the placebo. Another five patients showed MRI progression together with relapses. Three of these patients had received erythropoietin, and two the placebo. Yet, analyzing the change in absolute numbers of periventricular, juxtacortical, and infratentorial lesions including gadolinium-enhancing lesions, there were no significant differences between the groups. Although effective in terms of retinal nerve fiber layer protection, erythropoietin treatment of acute isolated optic neuritis did not influence further evolution of MRI lesions in the brain when comparing absolute numbers. However, early conversion from clinically isolated syndrome to MS assessed by MRI activity seemed to occur more frequently in the placebo-treated group.

  8. Disease Activity and Conversion into Multiple Sclerosis after Optic Neuritis Is Treated with Erythropoietin

    Science.gov (United States)

    Sühs, Kurt-Wolfram; Papanagiotou, Panagiotis; Hein, Katharina; Pul, Refik; Scholz, Kerstin; Heesen, Christoph; Diem, Ricarda

    2016-01-01

    Changes in cerebral lesion load by magnetic resonance imaging (MRI) in patients from a double-blind, placebo-controlled, phase II study on erythropoietin in clinically isolated optic neuritis (ClinicalTrials.gov, NCT00355095) were analyzed. Therefore, patients with acute optic neuritis were assigned to receive either 33,000 IU of recombinant human erythropoietin (IV) daily for three days, or a placebo, as an add-on to methylprednisolone. Of 35 patients, we investigated changes in cerebral lesion load in MRIs obtained at baseline and at weeks 4, 8, and 16. In 5 of the 35 patients, we found conversion into multiple sclerosis (MS) based on MRI progression only. These five patients had received the placebo. Another five patients showed MRI progression together with relapses. Three of these patients had received erythropoietin, and two the placebo. Yet, analyzing the change in absolute numbers of periventricular, juxtacortical, and infratentorial lesions including gadolinium-enhancing lesions, there were no significant differences between the groups. Although effective in terms of retinal nerve fiber layer protection, erythropoietin treatment of acute isolated optic neuritis did not influence further evolution of MRI lesions in the brain when comparing absolute numbers. However, early conversion from clinically isolated syndrome to MS assessed by MRI activity seemed to occur more frequently in the placebo-treated group. PMID:27706045

  9. Multiple dynamo modes as a mechanism for long-term solar activity variations

    CERN Document Server

    Käpylä, Maarit J; Olspert, Nigul; Brandenburg, Axel; Warnecke, Jörn; Karak, Bidya B; Pelt, Jaan

    2015-01-01

    Solar magnetic activity shows both smooth secular changes, such as the Grand Modern Maximum, and quite abrupt drops that are denoted as Grand Minima. Direct numerical simulations (DNS) of convection drivendynamos offer one way of examining the mechanisms behind these events. In this work, we analyze a solution of a solar-like DNS that has been evolved for roughly 80 magnetic cycles of 5.4 years, during which epochs of irregular behavior are detected. The emphasis of our analysis is to find physical causes for such behavior. The DNS employed is a semi-global (wedge) magnetoconvection model. For data analysis we use Ensemble Empirical Mode Decomposition (EEMD) and phase dispersion (D^2) methods. A special property of the DNS is the existence of multiple dynamo modes at different depths and latitudes. The dominant mode is solar-like. This mode is accompanied by a higher frequency mode near the surface and a low-frequency mode in the bottom of the convection zone. The overall behavior of the dynamo solution is ve...

  10. Mediators of Physical Activity on Neurocognitive Function: A Review at Multiple Levels of Analysis

    Directory of Open Access Journals (Sweden)

    Chelsea M. Stillman

    2016-12-01

    Full Text Available Physical activity (PA is known to maintain and improve neurocognitive health. However, there is still a poor understanding of the mechanisms by which PA exerts its effects on the brain and cognition in humans. Many of the most widely discussed mechanisms of PA are molecular and cellular and arise from animal models. While information about basic cellular and molecular mechanisms is an important foundation from which to build our understanding of how PA promotes cognitive health in humans, there are other pathways that could play a role in this relationship. For example, PA-induced changes to cellular and molecular pathways likely initiate changes to macroscopic properties of the brain and/or to behavior that in turn influence cognition. The present review uses a more macroscopic lens to identify potential brain and behavioral/socioemotional mediators of the association between PA and cognitive function. We first summarize what is known regarding cellular and molecular mechanisms, and then devote the remainder of the review to discussing evidence for brain systems and behavioral/socioemotional pathways by which PA influences cognition. It is our hope that discussing mechanisms at multiple levels of analysis will stimulate the field to examine both brain and behavioral mediators. Doing so is important, as it could lead to a more complete characterization of the processes by which PA influences neurocognitive function, as well as a greater variety of targets for modifying neurocognitive function in clinical contexts.

  11. Factorial combinations of protein interactions generate a multiplicity of florigen activation complexes in wheat and barley.

    Science.gov (United States)

    Li, Chengxia; Lin, Huiqiong; Dubcovsky, Jorge

    2015-10-01

    The FLOWERING LOCUS T (FT) protein is a central component of a mobile flowering signal (florigen) that is transported from leaves to the shoot apical meristem (SAM). Two FT monomers and two DNA-binding bZIP transcription factors interact with a dimeric 14-3-3 protein bridge to form a hexameric protein complex. This complex, designated as the 'florigen activation complex' (FAC), plays a critical role in flowering. The wheat homologue of FT, designated FT1 (= VRN3), activates expression of VRN1 in the leaves and the SAM, promoting flowering under inductive long days. In this study, we show that FT1, other FT-like proteins, and different FD-like proteins, can interact with multiple wheat and barley 14-3-3 proteins. We also identify the critical amino acid residues in FT1 and FD-like proteins required for their interactions, and demonstrate that 14-3-3 proteins are necessary bridges to mediate the FT1-TaFDL2 interaction. Using in vivo bimolecular fluorescent complementation (BiFC) assays, we demonstrate that the interaction between FT1 and 14-3-3 occurs in the cytoplasm, and that this complex is then translocated to the nucleus, where it interacts with TaFDL2 to form a FAC. We also demonstrate that a FAC including FT1, TaFDL2 and Ta14-3-3C can bind to the VRN1 promoter in vitro. Finally, we show that relative transcript levels of FD-like and 14-3-3 genes vary among tissues and developmental stages. Since FD-like proteins determine the DNA specificity of the FACs, variation in FD-like gene expression can result in spatial and temporal modulation of the effects of mobile FT-like signals.

  12. Mitochondrial DNA Activates the NLRP3 Inflammasome and Predisposes to Type 1 Diabetes in Murine Model

    Science.gov (United States)

    Carlos, Daniela; Costa, Frederico R. C.; Pereira, Camila A.; Rocha, Fernanda A.; Yaochite, Juliana N. U.; Oliveira, Gabriela G.; Carneiro, Fernando S.; Tostes, Rita C.; Ramos, Simone G.; Zamboni, Dario S.; Camara, Niels O. S.; Ryffel, Bernhard; Silva, João S.

    2017-01-01

    Although a correlation between polymorphisms of NOD-like receptor family-pyrin domain containing 3 (NLRP3) and predisposition to type 1 diabetes (T1D) has been identified, the potential function and activation of the NLRP3 inflammasome in T1D have not been clarified. The present study shows that non-obese diabetic mice exhibited increased NLRP3, and pro-IL-1β gene expression in pancreatic lymph nodes (PLNs). Similar increases in gene expression of NLRP3, apoptosis associated speck like protein (ASC) and pro-IL-1β were induced by multiple low doses of streptozotocin (STZ) in C57BL/6 mice. In addition, diabetic C57BL/6 mice also exhibited increased IL-1β protein expression in the pancreatic tissue at day 7, which remained elevated until day 15. Diabetic mice also showed increased positive caspase-1 macrophages in the PLNs, which were decreased in NLRP3−/− mice, but not in ASC−/− mice, after STZ treatment. NLRP3- and IL-1R-deficient mice, but not ASC-deficient mice, showed reduced incidence of diabetes, less insulitis, lower hyperglycemia, and normal insulin levels compared to wild-type (WT) diabetic mice. Notably, these mice also displayed a decrease in IL-17-producing CD4 and CD8 T cells (Th17 and Tc17) and IFN-γ-producing CD4 and CD8 T cells (Th1 and Tc1) in the PLNs. Following STZ treatment to induce T1D, NLRP3-deficient mice also exhibited an increase in myeloid-derived suppressor cell and mast cell numbers in the PLNs along with a significant increase in IL-6, IL-10, and IL-4 expression in the pancreatic tissue. Interestingly, diabetic mice revealed increased circulating expression of genes related to mitochondrial DNA, such as cytochrome b and cytochrome c, but not NADH dehydrogenase subunit 6 (NADH). Mitochondrial DNA (mDNA) from diabetic mice, but not from non-diabetic mice, induced significant IL-1β production and caspase-1 activation by WT macrophages, which was reduced in NLRP3−/− macrophages. Finally, mDNA administration in vivo increased

  13. Effects of supported (nBuCp)2ZrCl2 catalyst active center multiplicity on crystallization kinetics of ethylene homo- and copolymers

    KAUST Repository

    Atiqullah, Muhammad

    2014-07-01

    Two different supported zirconocene, that is, bis(n-butylcyclopentadienyl) zirconium dichloride (nBuCp)2ZrCl2, catalysts were synthesized. Each catalyst was used to prepare one ethylene homopolymer and one ethylene-1-hexene copolymer. Catalyst active center multiplicity and polymer crystallization kinetics were modeled. Five separate active center types were predicted, which matched the successive self-nucleation and annealing (SSA) peak temperatures. The predicted crystallinity well matched the differential scanning calorimetric (DSC) values for a single Avrami-Erofeev index, which ranged between 2 and 3 for the polymers experimented. The estimated apparent crystallization activation energy Ea did not vary with cooling rates, relative crystallinity α, and crystallization time or temperature. Therefore, the concept of variable/instantaneous activation energy was not found to hold. Ea linearly increased with the weight average lamellar thickness Lwav DSC-GT; and for each homopolymer, it exceeded that of the corresponding copolymer. Higher Ea, hence slower crystallization, was identified as a pre-requisite to attain higher crystallinity. Crystallization parameters were correlated to polymer backbone parameters, which are influenced by catalyst active center multiplicity. © 2013 Taiwan Institute of Chemical Engineers.

  14. Risk Profiles and Penetrance Estimations in Multiple Endocrine Neoplasia Type 2A Caused by Germline RET Mutations Located in Exon 10

    NARCIS (Netherlands)

    Frank-Raue, Karin; Rybicki, Lisa A.; Erlic, Zoran; Schweizer, Heiko; Winter, Aurelia; Milos, Ioana; Toledo, Sergio P. A.; Toledo, Rodrigo A.; Tavares, Marcos R.; Alevizaki, Maria; Mian, Caterina; Siggelkow, Heide; Huefner, Michael; Wohllk, Nelson; Opocher, Giuseppe; Dvorakova, Sarka; Bendlova, Bela; Czetwertynska, Malgorzata; Skasko, Elzbieta; Barontini, Marta; Sanso, Gabriela; Vorlaender, Christian; Maia, Ana Luiza; Patocs, Attila; Links, Thera P.; de Groot, Jan Willem; Kerstens, Michiel N.; Valk, Gerlof D.; Miehle, Konstanze; Musholt, Thomas J.; Biarnes, Josefina; Damjanovic, Svetozar; Muresan, Mihaela; Wuester, Christian; Fassnacht, Martin; Peczkowska, Mariola; Fauth, Christine; Golcher, Henriette; Walter, Martin A.; Pichl, Josef; Raue, Friedhelm; Eng, Charis; Neumann, Hartmut P. H.

    2011-01-01

    Multiple endocrine neoplasia type 2 is characterized by germline mutations in RET. For exon 10, comprehensive molecular and corresponding phenotypic data are scarce. The International RET Exon 10 Consortium, comprising 27 centers from 15 countries, analyzed patients with RET exon 10 mutations for cl

  15. Type D, anxiety and depression in association with quality of life in patients with Parkinson's disease and patients with multiple sclerosis

    NARCIS (Netherlands)

    Dubayova, Tatiana; Krokavcova, Martina; Nagyova, Iveta; Rosenberger, Jaroslav; Gdovinova, Zuzana; Middel, Berrie; Groothoff, Johan W.; van Dijk, Jitse P.

    2013-01-01

    The present study examines the role of Type D personality, anxiety and depression in quality of life (QoL) in patients with two chronic neurological diseases-Parkinson's disease (PD) and multiple sclerosis (MS). This cross-sectional study included 142 PD patients (73 % males; mean age 67.6 +/- A 9.2

  16. Measuring the Consistency in Change in Hepatitis B Knowledge among Three Different Types of Tests: True/False, Multiple Choice, and Fill in the Blanks Tests.

    Science.gov (United States)

    Sahai, Vic; Demeyere, Petra; Poirier, Sheila; Piro, Felice

    1998-01-01

    The recall of information about Hepatitis B demonstrated by 180 seventh graders was tested with three test types: (1) short-answer; (2) true/false; and (3) multiple-choice. Short answer testing was the most reliable. Suggestions are made for the use of short-answer tests in evaluating student knowledge. (SLD)

  17. Exclusion of the phosphatidylinositol-specific phospholipase C beta 3 (PLC beta 3) gene as candidate for the multiple endocrine neoplasia type 1 (MEN 1) gene

    NARCIS (Netherlands)

    de Wit, M J; Landsvater, R M; Sinke, R J; Geurts van Kessel, A; Lips, C J; Höppener, J W

    1997-01-01

    Multiple endocrine neoplasia type 1 (MEN 1) is inherited as an autosomal dominant disorder, characterized by hyperplasia and neoplasia in several endocrine organs. The MEN 1 gene, which is most probably a tumor suppressor gene, has been localized to a 900-kb region on chromosome 11q13. The human pho

  18. Somatic mutations of the RET proto-oncogene are not required for tumor development in multiple endocrine neoplasia type 2 (MEN 2) gene carriers

    NARCIS (Netherlands)

    Landsvater, RM; deWit, MJ; Zewald, RA; Hofstra, RMW; Buys, CHCM; vanAmstel, HKP; Hoppener, JWM; Lips, CJM

    1996-01-01

    Germ line mutations in one allele of the RET proto-oncogene predispose to the multiple endocrine neoplasia type 2 (MEN 2) syndromes, To investigate whether these inherited mutations alone can cause the development of tumors in vivo (oncogene model) or whether somatic mutations in the homologous RET

  19. Synthesis and biological activity of quaternary ammonium salt-type agents containing cholesterol and terpenes.

    Science.gov (United States)

    Novotná, Eva; Waisser, Karel; Kuneš, Jiří; Palát, Karel; Buchta, Vladimír; Stolaříková, Jiřina; Beckert, Rainer; Wsól, Vladimír

    2014-06-01

    New quaternary ammonium salt-type compounds with lipophilic cholesterol and terpene moieties were synthesized. The compounds showed promising antibacterial and antimycobacterial activities. Those compounds containing the cholesterol moiety showed significant activity against Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecium. On the contrary, the antimycobacterial activity increased with the presence of the terpene unit in the molecule.

  20. Design of heterogeneous catalysts via multiple active site positioning in organic-inorganic hybrid materials.

    Science.gov (United States)

    Dufaud, Véronique; Davis, Mark E

    2003-08-06

    Catalytic materials bearing multiple sulfonic acid functional groups and positioned at varying distances from one another on the surface of mesoporous solids are prepared to explore the effects that the spatial arrangement of active sites have on catalytic activity and selectivity. A series of organosiloxane precursors containing either disulfide or sulfonate ester functionalities (synthons of the eventual sulfonic acid groups) are synthesized. From these molecular precursors, a variety of organic-inorganic hybrid, mesostructured SBA-15 silica materials are prepared using a postsynthetic grafting procedure that leads to disulfide and sulfonate ester modified silicas: [Si]CH(2)CH(2)CH(2)SS-pyridyl, 2.SBA, [Si]CH(2)CH(2)CH(2)SSCH(2)CH(2)CH(2)[Si], 3.SBA, [Si]CH(2)CH(2)(C(6)H(4))(SO(2))OCH(2)CH(3), 4.SBA, and [Si]CH(2)CH(2)(C(6)H(4))(SO(2))OC(6)H(4)O(SO(2))(C(6)H(4))CH(2)CH(2)[Si], 6.SBA ([Si] = (tbd1;SiO)(x)()(RO)(3)(-)(x)()Si, where x = 1, 2). By subsequent chemical derivatization of the grafted species, thiol and sulfonic acid modified silicas are obtained. The materials are characterized by a variety of spectroscopic ((13)C and (29)Si CP MAS NMR, X-ray diffraction) and quantitative (TGA/DTA, elemental analysis, acid capacity titration) techniques. In all cases, the organic fragment of the precursor molecule is grafted onto the solid without measurable decomposition, and the precursors are, in general, attached to the surface of the mesoporous oxide by multiple siloxane bridges. The disulfide species 2.SBA and 3.SBA are reduced to the corresponding thiols 7.SBA and 8.SBA, respectively, and 4.SBA and 6.SBA are transformed to the aryl sulfonic acids 11.SBA and 12.SBA, respectively. 7.SBA and 8.SBA differ only in terms of the level of control of the spatial arrangement of the thiol groups. Both 7.SBA and 8.SBA are further modified by oxidation with hydrogen peroxide to produce the alkyl sulfonic acid modified materials 9.SBA and 10.SBA, respectively. The performances