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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

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    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.

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    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 endocrine neoplasia type 1

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    R V Thakker

    2012-01-01

    Full Text Available Multiple endocrine neoplasia type 1 (MEN1 is characterized by the occurrence of parathyroid, pancreatic islet and anterior pituitary tumors. Some patients may also develop carcinoid tumors, adrenocortical tumors, facial angiofibromas, collagenomas, and lipomas. MEN1 is an autosomal-dominant disorder, due to mutations in the tumor suppressor gene MEN1, which encodes a 610 amino acid protein, menin. Thus, the finding of MEN1 in a patient has important implications for family members because first-degree relatives have a 50% risk of developing the disease and can often be identified by MEN1 mutational analysis. Patients with MEN1 have a decreased life-expectancy and the outcomes of current treatments, which are generally similar to that for the respective tumors occurring in non-MEN1 patients, are not as successful because of multiple tumors, which may be larger, more aggressive, and resistant to treatment, and the concurrence of metastases. The prognosis for MEN1 patients might be improved by pre-symptomatic tumor detection and undertaking treatment specific for MEN1-tumors. Thus, it is recommended that MEN1 patients and their families should be cared for by multi-disciplinary teams comprising relevant specialists with experience in the diagnosis and treatment of patients with endocrine tumors.

  8. 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

    of the long fatty acid (C24:0), resulted in reduced stimulatory capacity, and fatty acid hydroxylation abolished the response. Moreover, sulfatide was not responsible for the natural autoreactivity toward splenocytes by XV19 T hybridoma cells. Our results reveal a promiscuity in the recognition of sulfatide...... 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.......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...

  9. Multiple endocrine neoplasia type 1

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    Luzi Ettore

    2006-10-01

    Full Text Available Abstract Multiple Endocrine Neoplasia type 1 (MEN1 is a rare autosomal dominant hereditary cancer syndrome presented mostly by tumours of the parathyroids, endocrine pancreas and anterior pituitary, and characterised by a very high penetrance and an equal sex distribution. It occurs in approximately one in 30,000 individuals. Two different forms, sporadic and familial, have been described. The sporadic form presents with two of the three principal MEN1-related endocrine tumours (parathyroid adenomas, entero-pancreatic tumours and pituitary tumours within a single patient, while the familial form consists of a MEN1 case with at least one first degree relative showing one of the endocrine characterising tumours. Other endocrine and non-endocrine lesions, such as adrenal cortical tumours, carcinoids of the bronchi, gastrointestinal tract and thymus, lipomas, angiofibromas, collagenomas have been described. The responsible gene, MEN1, maps on chromosome 11q13 and encodes a 610 aminoacid nuclear protein, menin, with no sequence homology to other known human proteins. MEN1 syndrome is caused by inactivating mutations of the MEN1 tumour suppressor gene. This gene is probably involved in the regulation of several cell functions such as DNA replication and repair and transcriptional machinery. The combination of clinical and genetic investigations, together with the improving of molecular genetics knowledge of the syndrome, helps in the clinical management of patients. Treatment consists of surgery and/or drug therapy, often in association with radiotherapy or chemotherapy. Currently, DNA testing allows the early identification of germline mutations in asymptomatic gene carriers, to whom routine surveillance (regular biochemical and/or radiological screenings to detect the development of MEN1-associated tumours and lesions is recommended.

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

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    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.

  11. Multiple Endocrine Neoplasia Type I

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    ... treatment as needed. References [1] White ML, Doherty GM. Multiple endocrine neoplasia. Surgical Oncology Clinics of North ... for questions about any medications, contact the U.S. Food and Drug Administration toll-free at 1-888- ...

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

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    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.

  13. Multiple active myofascial trigger points and pressure pain sensitivity maps in the temporalis muscle are related in women with chronic tension type headache.

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    Fernández-de-las-Peñas, César; Caminero, Ana B; Madeleine, Pascal; Guillem-Mesado, Amparo; Ge, Hong-You; Arendt-Nielsen, Lars; Pareja, Juan A

    2009-01-01

    To describe the common locations of active trigger points (TrPs) in the temporalis muscle and their referred pain patterns in chronic tension type headache (CTTH), and to determine if pressure sensitivity maps of this muscle can be used to describe the spatial distribution of active TrPs. Forty women with CTTH were included. An electronic pressure algometer was used to assess pressure pain thresholds (PPT) from 9 points over each temporalis muscle: 3 points in the anterior, medial and posterior part, respectively. Both muscles were examined for the presence of active TrPs over each of the 9 points. The referred pain pattern of each active TrP was assessed. Two-way analysis of variance detected significant differences in mean PPT levels between the measurement points (F=30.3; P<0.001), but not between sides (F=2.1; P=0.2). PPT scores decreased from the posterior to the anterior column (P<0.001). No differences were found in the number of active TrPs (F=0.3; P=0.9) between the dominant side the nondominant side. Significant differences were found in the distribution of the active TrPs (chi2=12.2; P<0.001): active TrPs were mostly found in the anterior column and in the middle of the muscle belly. The analysis of variance did not detect significant differences in the referred pain pattern between active TrPs (F=1.1, P=0.4). The topographical pressure pain sensitivity maps showed the distinct distribution of the TrPs indicated by locations with low PPTs. Multiple active TrPs in the temporalis muscle were found, particularly in the anterior column and in the middle of the muscle belly. Bilateral posterior to anterior decreased distribution of PPTs in the temporalis muscle in women with CTTH was found. The locations of active TrPs in the temporalis muscle corresponded well to the muscle areas with lower PPT, supporting the relationship between multiple active muscle TrPs and topographical pressure sensitivity maps in the temporalis muscle in women with CTTH.

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

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    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.

  15. Adeno-associated virus type 2 infection activates caspase dependent and independent apoptosis in multiple breast cancer lines but not in normal mammary epithelial cells

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    Tandon Apurva

    2011-08-01

    Full Text Available Abstract Background In normal cells proliferation and apoptosis are tightly regulated, whereas in tumor cells the balance is shifted in favor of increased proliferation and reduced apoptosis. Anticancer agents mediate tumor cell death via targeting multiple pathways of programmed cell death. We have reported that the non-pathogenic, tumor suppressive Adeno-Associated Virus Type 2 (AAV2 induces apoptosis in Human Papillomavirus (HPV positive cervical cancer cells, but not in normal keratinocytes. In the current study, we examined the potential of AAV2 to inhibit proliferation of MCF-7 and MDA-MB-468 (both weakly invasive, as well as MDA-MB-231 (highly invasive human breast cancer derived cell lines. As controls, we used normal human mammary epithelial cells (nHMECs isolated from tissue biopsies of patients undergoing breast reduction surgery. Results AAV2 infected MCF-7 line underwent caspase-independent, and MDA-MB-468 and MDA-MB-231 cell lines underwent caspase-dependent apoptosis. Death of MDA-MB-468 cells was marked by caspase-9 activation, whereas death of MDA-MB-231 cells was marked by activation of both caspase-8 and caspase-9, and resembled a mixture of apoptotic and necrotic cell death. Cellular demise was correlated with the ability of AAV2 to productively infect and differentially express AAV2 non-structural proteins: Rep78, Rep68 and Rep40, dependent on the cell line. Cell death in the MCF-7 and MDA-MB-231 lines coincided with increased S phase entry, whereas the MDA-MB-468 cells increasingly entered into G2. AAV2 infection led to decreased cell viability which correlated with increased expression of proliferation markers c-Myc and Ki-67. In contrast, nHMECs that were infected with AAV2 failed to establish productive infection or undergo apoptosis. Conclusion AAV2 regulated enrichment of cell cycle check-point functions in G1/S, S and G2 phases could create a favorable environment for Rep protein expression. Inherent Rep associated

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

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    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...

  17. 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.

  18. 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...... on national age, sex, and period-specific MS and T1D incidence rates. RESULTS: Patients with T1D were at more than 3-fold increased risk for development of MS (relative risk, 3.26; 95% confidence interval, 1.80-5.88; n = 11). First-degree relatives of patients with MS were at 63% increased risk (relative risk......, 1.63; 95% confidence interval, 1.26-2.12; n = 56) for development of T1D. However, adjusting for familial relationship to patients with T1D reduced the excess risk to 44% (relative risk, 1.44; 95% confidence interval, 1.11-1.88; n = 56). CONCLUSION: The present nationwide cohort study demonstrates...

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

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    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.

  20. Genetics of Multiple Endocrine Neoplasia Type 1/Multiple Endocrine Neoplasia Type 2 Syndromes.

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    Hyde, Samuel M; Cote, Gilbert J; Grubbs, Elizabeth G

    2017-06-01

    Multiple endocrine neoplasia syndromes types 1 and 2 represent well-characterized yet clinically heterogeneous hereditary conditions for which diagnostic and management recommendations exist; genetic testing for these inherited endocrinopathies is included in these guidelines and is an important part of identifying affected patients and their family members. Understanding of these mature syndromes is challenged as more individuals undergo genetic testing and genetic data are amassed, with the potential to create clinical conundrums that may have an impact on individualized approaches to management and counseling. Clinicians who diagnose and treat patients with MEN syndromes should be aware of these possibilities. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. 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.

  2. 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.

  3. Diabetes Type 2 - Multiple Languages: MedlinePlus

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    ... 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 ...

  4. 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...

  5. 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...

  6. 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.}

  7. 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

  8. 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.

  9. 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)

  10. 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.

  11. 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.

  12. 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.

  13. Surgical intervention in children with multiple endocrine neoplasia type 2.

    Science.gov (United States)

    Danko, Melissa E; Skinner, Michael A

    2006-06-01

    We provide a summary of the literature published in the past year addressing the surgical approach to multiple endocrine neoplasia type 2 in the pediatric population. The review focuses first on medullary thyroid carcinoma and performing prophylactic thyroidectomy for the prevention or cure of this disease. The timing and extent of surgery as well as additional surgical intervention for persistent or recurrent disease is discussed. Then the surgical management of hereditary pheochromocytoma is reviewed. Surgery is often the only treatment that can prevent or cure the endocrinopathies associated with multiple endocrine neoplasia type 2. Determining the proper timing and extent of surgical intervention in children affected with multiple endocrine neoplasia type 2 will lead to better outcomes and survival.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    NARCIS (Netherlands)

    Nell, Sjoerd; van Leeuwaarde, Rachel S; Pieterman, Carolina R C; de Laat, Joanne M; Hermus, Ad R; Dekkers, Olaf M; de Herder, Wouter W; van der Horst-Schrivers, Anouk N; Drent, Madeleine L; Bisschop, Peter H; Havekes, Bas; Borel Rinkes, Inne H M; Vriens, Menno R; Valk, Gerlof D.

    2015-01-01

    CONTEXT: An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore,

  19. No Association of Blood Type O With Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    NARCIS (Netherlands)

    Nell, Sjoerd; Van Leeuwaarde, Rachel S.; Pieterman, Carolina R. C.; de Laat, Joanne M.; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Rinkes, Inne H. M. Borel; Vriens, Menno R.; Valk, Gerlof D.

    2015-01-01

    Context: An association between ABO blood type and the development of cancer, in particular, pancreatic cancer, has been reported in the literature. An association between blood type O and neuroendocrine tumors in multiple endocrine neoplasia type 1 (MEN1) patients was recently suggested. Therefore,

  20. 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.

  1. 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.

  2. 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.

  3. Gastroenteropancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1

    Energy Technology Data Exchange (ETDEWEB)

    Tonelli, Francesco, E-mail: f.tonelli@dfc.unifi.it; Giudici, Francesco [Department of Clinical Physiopathology, Surgical Unit, Medical School, University of Florence, Largo Brambilla n° 3, Florence 50134 (Italy); Giusti, Francesca; Brandi, Maria Luisa [Department of Internal Medicine, Medical School and Regional Centre for Hereditary Endocrine Tumors, University of Florence, Largo Brambilla n° 3, Florence 50134 (Italy)

    2012-05-07

    We reviewed the literature about entero-pancreatic neuroendocrine tumors in Multiple Endocrine Neoplasia type 1 syndrome (MEN1) to clarify their demographic features, localization imaging, practice, and appropriate therapeutical strategies, analyzing the current approach to entero-pancreatic neuroendocrine tumors in MEN1. Despite the fact that hyperparathyroidism is usually the first manifestation of MEN1, the penetrance of these tumors is similar. They are characterized by multiplicity of lesions, variable expression of the tumors, and propensity for malignant degeneration. Both the histological type and the size of MEN1 neuroendocrine tumors correlate with malignancy. Monitoring of pancreatic peptides and use of imaging exams allow early diagnosis and prompt surgical treatment, resulting in prevention of metastatic disease and improvement of long-term survival. Surgery is often the treatment of choice for MEN1-neuroendocrine tumors. The rationale for surgical approach is to curtail malignant progression of the disease, and to cure the associated biochemical syndrome, should it be present.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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

  12. 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.

  13. 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.

  14. 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

  15. 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...

  16. 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

  17. 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…

  18. 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.

  19. Glycoside hydrolases having multiple hydrolase activities

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zhiwei; Friedland, Gregory D.; Chhabra, Swapnil R.; Chivian, Dylan C.; Simmons, Blake A

    2017-08-08

    Glycoside hydrolases having at least two different hydrolytic activities are provided. In one embodiment, an isolated recombinant hydrolase having at least two activities selected from a group including asparagine derivatives, glutamine derivatives, and histidine derivatives is provided. Further, a method of generating free sugars from a mixture comprising asparagine derivatives, glutamine derivatives, and histidine derivatives is provided.

  20. 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...

  1. 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.

  2. Imaging anisotropic layering with Bayesian inversion of multiple data types

    Science.gov (United States)

    Bodin, T.; Leiva, J.; Romanowicz, B.; Maupin, V.; Yuan, H.

    2016-07-01

    Azimuthal anisotropy is a powerful tool to reveal information about both the present structure and past evolution of the mantle. Anisotropic images of the upper mantle are usually obtained by analysing various types of seismic observables, such as surface wave dispersion curves or waveforms, SKS splitting data, or receiver functions. These different data types sample different volumes of the earth, they are sensitive to different length scales, and hence are associated with different levels of uncertainties. They are traditionally interpreted separately, and often result in incompatible models. We present a Bayesian inversion approach to jointly invert these different data types. Seismograms for SKS and P phases are directly inverted using a cross-convolution approach, thus avoiding intermediate processing steps, such as numerical deconvolution or computation of splitting parameters. Probabilistic 1-D profiles are obtained with a transdimensional Markov chain Monte Carlo scheme, in which the number of layers, as well as the presence or absence of anisotropy in each layer, are treated as unknown parameters. In this way, seismic anisotropy is only introduced if required by the data. The algorithm is used to resolve both isotropic and anisotropic layering down to a depth of 350 km beneath two seismic stations in North America in two different tectonic settings: the stable Canadian shield (station FFC) and the tectonically active southern Basin and Range Province (station TA-214A). In both cases, the lithosphere-asthenosphere boundary is clearly visible, and marked by a change in direction of the fast axis of anisotropy. Our study confirms that azimuthal anisotropy is a powerful tool for detecting layering in the upper mantle.

  3. 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

  4. 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.

  5. 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.

  6. 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.

  7. Multiple types of psychological contracts : a six-cluster solution.

    OpenAIRE

    Van Den Brande, I; Janssens, Maddy; Sels, Luc; Overlaet, Robrecht

    2002-01-01

    The purpose of this study is to empirically examine the existence of particular types of psychological contracts. We take a feature-oriented approach towards psychological contracts, which allows more generalizability across settings than content-oriented assessments. In defining the types of psychological contracts, we rely on 10 dimensions that indicate the employees' expected entitlements as well as their expected obligations towards their employer. We assess the existence of types of psyc...

  8. 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.

  9. 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

  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 ▿

    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

  11. 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

    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......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...... live in such an environment. Recognizing activities of not only a single user, but also multiple users is essential to the development of practical context-aware applications in pervasive computing. In this paper, we investigate the fundamental problem of recognizing activities for multiple users from...

  12. 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.

  13. 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.

  14. Neurofibromatosis type 1 and multiple sclerosis: Genetically related ...

    African Journals Online (AJOL)

    Solaf M. Elsayed

    2016-10-25

    Oct 25, 2016 ... Abstract Neurofibromatosis type I (NF1) is an autosomal dominant disorder with involvement of ... sense of pins and needles in lower limbs up to her knees. It .... relapsing MS which is also progressive in nature from the start.

  15. 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...

  16. 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.

  17. 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.

  18. 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...

  19. Low leucocyte myeloperoxidase activity in patients with multiple sclerosis

    NARCIS (Netherlands)

    Ramsaransing, G; Teelken, A; Prokopenko, VM; Arutjunyan, AV; De Keyser, J

    2003-01-01

    The gene for myeloperoxidase (MPO) has been implicated in multiple sclerosis (MS). By measuring H2O2 dependent oxidation of 3,3'5,5'-tetramethylbenzidine with spectrophotometry the authors investigated MPO activity in peripheral blood leucocytes from 42 patients with MS (12 with secondary progressiv

  20. 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

  1. 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.

  2. 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

  3. Complex Dynamic Scene Perception: Effects of Attentional Set on Perceiving Single and Multiple Event Types

    Science.gov (United States)

    Sanocki, Thomas; Sulman, Noah

    2013-01-01

    Three experiments measured the efficiency of monitoring complex scenes composed of changing objects, or events. All events lasted about 4 s, but in a given block of trials, could be of a single type (single task) or of multiple types (multitask, with a total of four event types). Overall accuracy of detecting target events amid distractors was…

  4. Multiple endocrine neoplasia type 2A: a 25-year review.

    Science.gov (United States)

    Iler, M A; King, D R; Ginn-Pease, M E; O'Dorisio, T M; Sotos, J F

    1999-01-01

    Before 1970, treatment decisions for the thyroid lesions in patients with multiple endocrine neoplasia (MEN) were based on physical findings. For the next 20 years, biological markers assumed a preeminent role, and at present, DNA testing is being used to define the need for therapeutic intervention. This report presents a 25-year review of 22 children with MEN-2A, with a mean follow-up of 12.5 years. All 22 children underwent a total thyroidectomy, and four (18%) were rendered permanently hypoparathyroid. Since 1976, however, only one patient (6.7%) has lost parathyroid function. Despite the fact that biological screening studies routinely were performed once a year in the majority of our patients and surgery was recommended for any elevation in the serum calcitonin (CT) levels, medullary carcinoma of the thyroid (MTC) developed in 17 children (77%) and only five had C cell hyperplasia (CCH). Thirteen of the 17 had macroscopic tumor described by the pathologist, evidence of recurrent disease (MTC-REC) has developed in four children (24%). There was considerable overlap in both the basal and stimulated CT levels among the five children with CCH, the 13 with localized MTC (MTC-NED), and the four who later had recurrent MTC. The basal calcitonin levels were between 25 and 110 (mean, 58) in the CCH patients, 30 to 1,130 (mean, 184) in the MTC-NED group, and 108 to 201 (mean, 140) in those with recurrent MTC. The corresponding stimulated calcitonin levels were 45 to 417 (mean, 179) in CCH, 111 to 9,510 (mean, 1,407) in MTC-NED, and 449 to 5,093 (mean, 3,383) in MTC-REC. (1) Basal and pentagastrin-stimulated CT levels did not reliably discriminate between CCH and MTC and should not be used to define the timing of thyroid surgery in children with MEN-2A. (2) Surgical therapy should be undertaken early in childhood on the basis of molecular genetic testing. (3) Postoperative complications are infrequent in the modern era.

  5. 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.

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

    Institute of Scientific and Technical Information of China (English)

    Wang Feng; Zhang Fang; Liu Chunhan

    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.

  7. 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.

  8. 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.

  9. Local recurrence of pheochromocytoma in multiple endocrine neoplasia type 2A: a diagnostic and therapeutic challenge

    OpenAIRE

    Tramunt, Blandine; Buffet, Alexandre; Grunenwald, Solange; Vezzosi, Delphine; Bennet, Antoine; Huyghe, Eric; Zerdoud, Slimane; Caron, Philippe

    2016-01-01

    Key Clinical Message In a patient with multiple endocrine neoplasia type 2A (MEN2A), an inverted physiological ratio between urinary normetanephrines and metanephrines is an early marker of recurrence in epinephrine?secreting pheochromocytoma, and 131I MIBG treatment appears to be a useful therapeutic option in order to avoid multiple invasive surgical procedures in pheochromocytomatosis.

  10. Local recurrence of pheochromocytoma in multiple endocrine neoplasia type 2A: a diagnostic and therapeutic challenge.

    Science.gov (United States)

    Tramunt, Blandine; Buffet, Alexandre; Grunenwald, Solange; Vezzosi, Delphine; Bennet, Antoine; Huyghe, Eric; Zerdoud, Slimane; Caron, Philippe

    2016-03-01

    In a patient with multiple endocrine neoplasia type 2A (MEN2A), an inverted physiological ratio between urinary normetanephrines and metanephrines is an early marker of recurrence in epinephrine-secreting pheochromocytoma, and 131I MIBG treatment appears to be a useful therapeutic option in order to avoid multiple invasive surgical procedures in pheochromocytomatosis.

  11. 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...

  12. 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.

  13. CpG Type A Induction of an Early Protective Environment in Experimental Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    James Crooks

    2017-01-01

    Full Text Available Experimental autoimmune encephalomyelitis (EAE is an inflammatory, demyelinating disease of the CNS that mimics human multiple sclerosis (MS, and it is thought to be driven by Th1 and Th17 myelin-reactive cells. Although adaptive immunity is clearly pivotal in the pathogenesis of EAE, with an essential role of CD4+ T cells, little is known of early, innate responses in this experimental setting. CpG-rich oligodeoxynucleotides (ODNs, typically found in microbial genomes, are potent activators of TLR9 in plasmacytoid dendritic cells (pDCs. In this study, we compared the effects of two types of CpG, namely, type A and type B, on EAE. We found that treatment with CpG type A ODN (CpG-A, known to induce high amounts of IFN-α in pDCs, significantly reduced disease severity in EAE, relative to controls (12.63±1.86 versus 23.49±1.46, resp.; p=0.001. Treatment also delayed onset of neurological deficits and reduced spinal cord demyelination, while increasing the percentage of splenic regulatory (Foxp3+ CD4+ T cells. CpG-A likewise reduced the levels of IL-17 and IFN-γ in the CNS. Mechanistic insight into those events showed that CpG-A promoted a regulatory phenotype in pDCs. Moreover, adoptive transfer of pDCs isolated from CpG-A-treated mice inhibited CNS inflammation and induced disease remission in acute-phase EAE. Our data thus identify a link between TLR9 activation by specific ligands and the induction of tolerance via innate immunity mechanisms.

  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...... 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...... 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...

  16. 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.

  17. 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

  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. Relationship between pulmonary and systemic markers of exposure to multiple types of welding particulate matter.

    Science.gov (United States)

    Erdely, Aaron; Salmen-Muniz, Rebecca; Liston, Angie; Hulderman, Tracy; Zeidler-Erdely, Patti C; Antonini, James M; Simeonova, Petia P

    2011-09-05

    Welding results in a unique and complex occupational exposure. Recent epidemiological studies have shown an increased risk of cardiovascular disease following welding fume exposure. In this study, we compared the induction of pulmonary and systemic inflammation following exposure to multiple types of welding fumes. Mice were exposed to 340μg of manual metal arc stainless steel (MMA-SS), gas metal arc-SS (GMA-SS) or GMA-mild steel (GMA-MS) by pharyngeal aspiration. Mice were sacrificed at 4 and 24h post-exposure to evaluate various parameters of pulmonary and systemic inflammation. Alterations in pulmonary gene expression by a custom designed TaqMan array showed minimal differences between the fumes at 4h. Conversely at 24h, gene expression changes were further increased by SS but not GMA-MS exposure. These findings were associated with the surrogate marker of systemic inflammation, liver acute phase gene induction. Interestingly, stress response genes in cardiovascular tissues were only increased following MMA-SS exposure. These effects were related to the initial level of pulmonary cytotoxicity, as measured by lactate dehydrogenase activity, which was greatest following MMA-SS exposure. In conclusion, varying types of welding fumes elicit quantitatively different systemic inflammatory and/or stress responses. Published by Elsevier Ireland Ltd.

  20. Due-Window Assignment and Scheduling with Multiple Rate-Modifying Activities under the Effects of Deterioration and Learning

    Directory of Open Access Journals (Sweden)

    Zhanguo Zhu

    2011-01-01

    Full Text Available This paper discusses due-window assignment and scheduling with multiple rate-modifying activities. Multiple types of rate-modifying activities are allowed to perform on a single machine. The learning effect and job deterioration are also integrated concurrently into the problem which makes the problem more realistic. The objective is to find jointly the optimal location to perform multiple rate-modifying activities, the optimal job sequence, and the optimal location and size of the due window to minimize the total earliness, tardiness, and due-window-related costs. We propose polynomial time algorithms for all the cases of the problem under study.

  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. 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.

  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

    2017-01-01

    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

  7. Activities-Specific Balance Confidence in People with Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Ylva Nilsagård

    2012-01-01

    Full Text Available 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 Gocog, 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.

  8. 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.

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

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    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

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

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    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. 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.

  12. Stress and radiation-induced activation of multiple intracellular signaling pathways.

    Science.gov (United States)

    Dent, Paul; Yacoub, Adly; Contessa, Joseph; Caron, Ruben; Amorino, George; Valerie, Kristoffer; Hagan, Michael P; Grant, Steven; Schmidt-Ullrich, Rupert

    2003-03-01

    Exposure of cells to a variety of stresses induces compensatory activations of multiple intracellular signaling pathways. These activations can play critical roles in controlling cell survival and repopulation effects in a stress-specific and cell type-dependent manner. Some stress-induced signaling pathways are those normally activated by mitogens such as the EGFR/RAS/PI3K-MAPK pathway. Other pathways activated by stresses such as ionizing radiation include those downstream of death receptors, including pro-caspases and the transcription factor NFKB. This review will attempt to describe some of the complex network of signals induced by ionizing radiation and other cellular stresses in animal cells, with particular attention to signaling by growth factor and death receptors. This includes radiation-induced signaling via the EGFR and IGFI-R to the PI3K, MAPK, JNK, and p38 pathways as well as FAS-R and TNF-R signaling to pro-caspases and NFKB. The roles of autocrine ligands in the responses of cells and bystander cells to radiation and cellular stresses will also be discussed. Based on the data currently available, it appears that radiation can simultaneously activate multiple signaling pathways in cells. Reactive oxygen and nitrogen species may play an important role in this process by inhibiting protein tyrosine phosphatase activity. The ability of radiation to activate signaling pathways may depend on the expression of growth factor receptors, autocrine factors, RAS mutation, and PTEN expression. In other words, just because pathway X is activated by radiation in one cell type does not mean that pathway X will be activated in a different cell type. Radiation-induced signaling through growth factor receptors such as the EGFR may provide radioprotective signals through multiple downstream pathways. In some cell types, enhanced basal signaling by proto-oncogenes such as RAS may provide a radioprotective signal. In many cell types, this may be through PI3K, in others

  13. 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.

  14. 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.

  15. 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.

  16. Insights into the emission reductions of multiple unintentional persistent organic pollutants from industrial activities.

    Science.gov (United States)

    Liu, Guorui; Zheng, Minghui; Jiang, Xiaoxu; Jin, Rong; Zhao, Yuyang; Zhan, Jiayu

    2016-02-01

    Industrial activities result in unintentional production of multiple types of persistent organic pollutants (POPs) at various concentrations. Because of the potential adverse effect of these POPs on the environment, biota and human health, methods for controlling emission of POPs are required. Development and application of techniques for controlling emissions of POPs can be a technical and economic burden for the industry involved. Therefore, from the point of view of cost-benefit analysis, reducing emissions of multiple pollutants at the same time is optimal for sustainable industrial development. Although techniques have been developed for reducing the emissions of individual POPs, such as dioxins, further work is required on multi-POP control emissions from industrial activities. This paper discusses three important aspects that need to be taken to achieve multi-POP control. These aspects include the establishment of a comprehensive system for evaluating the risk from emissions of multiple POPs, determination of indicators for total emissions of multiple POPs, and the preparation and application of functional materials to inhibit formation of multiple POPs. These discussion might be helpful for the future research on the multi-POP control in industry. Copyright © 2015 Elsevier Ltd. All rights reserved.

  17. BDNF val66met polymorphism affects aging of multiple types of memory.

    Science.gov (United States)

    Kennedy, Kristen M; Reese, Elizabeth D; Horn, Marci M; Sizemore, April N; Unni, Asha K; Meerbrey, Michael E; Kalich, Allan G; Rodrigue, Karen M

    2015-07-01

    The BDNF val66met polymorphism (rs6265) influences activity-dependent secretion of brain-derived neurotrophic factor in the synapse, which is crucial for learning and memory. Individuals homozygous or heterozygous for the met allele have lower BDNF secretion than val homozygotes and may be at risk for reduced declarative memory performance, but it remains unclear which types of declarative memory may be affected and how aging of memory across the lifespan is impacted by the BDNF val66met polymorphism. This cross-sectional study investigated the effects of BDNF polymorphism on multiple indices of memory (item, associative, prospective, subjective complaints) in a lifespan sample of 116 healthy adults aged 20-93 years. Advancing age showed a negative effect on item, associative and prospective memory, but not on subjective memory complaints. For item and prospective memory, there were significant age×BDNF group interactions, indicating the adverse effect of age on memory performance across the lifespan was much stronger in the BDNF met carriers than for the val homozygotes. BDNF met carriers also endorsed significantly greater subjective memory complaints, regardless of age, and showed a trend (pmemory performance compared to val homozygotes. These results suggest that genetic predisposition to the availability of brain-derived neurotrophic factor, by way of the BDNF val66met polymorphism, exerts an influence on multiple indices of episodic memory - in some cases in all individuals regardless of age (subjective memory and perhaps associative memory), in others as an exacerbation of age-related differences in memory across the lifespan (item and prospective memory). This article is part of a Special Issue entitled Memory & Aging. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. 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.

  19. 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.

  20. 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…

  1. 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.

  2. 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.

  3. Diagnosis and Management of Multiple Endocrine Neoplasia Type 1 (MEN1)

    NARCIS (Netherlands)

    Dreijerink, Koen M. A.; Lips, Cees J. M.

    2005-01-01

    Multiple endocrine neoplasia type 1 (MEN1) is an autosomal dominantly inherited disorder, characterised by the occurrence of tumours of the parathyroid glands, the pancreatic islets, the pituitary gland, the adrenal glands and neuroendocrine carcinoid tumours. Carcinoid tumours of the thymus and pan

  4. Characteristics of the Danish families with multiple endocrine neoplasia type 1

    DEFF Research Database (Denmark)

    2006-01-01

    Multiple endocrine neoplasia type 1 (MEN1) is caused by autosomal dominantly inherited mutations in the MEN1 gene. Here, we report 25 MEN1 mutations - of which 12 are novel - found in 36 Danish families with MEN1 or variant MEN1 disease. Furthermore, one FIHP family was found to have an earlier r...

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

    NARCIS (Netherlands)

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

  6. 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.

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. MMP-12 catalytic domain recognizes and cleaves at multiple sites in human skin collagen type I and type III.

    Science.gov (United States)

    Taddese, Samuel; Jung, Michael C; Ihling, Christian; Heinz, Andrea; Neubert, Reinhard H H; Schmelzer, Christian E H

    2010-04-01

    Collagens of either soft connective or mineralized tissues are subject to continuous remodeling and turnover. Undesired cleavage can be the result of an imbalance between proteases and their inhibitors. Owing to their superhelical structure, collagens are resistant to many proteases and matrix metalloproteinases (MMPs) are required to initiate further degradation by other enzymes. Several MMPs are known to degrade collagens, but the action of MMP-12 has not yet been studied in detail. In this work, the potential of MMP-12 in recognizing sites in human skin collagen types I and III has been investigated. The catalytic domain of MMP-12 binds to the triple helix and cleaves the typical sites -Gly(775)-Leu(776)- in alpha-2 type I collagen and -Gly(775)-Ile(776)- in alpha-1 type I and type III collagens and at multiple other sites in both collagen types. Moreover, it was observed that the region around these typical sites contains comparatively less prolines, of which some have been proven to be only partially hydroxylated. This is of relevance since partial hydroxylation in the vicinity of a potential scissile bond may have a local effect on the conformational thermodynamics with probable consequences on the collagenolysis process. Taken together, the results of the present work confirm that the catalytic domain of MMP-12 alone binds and degrades collagens I and III. Copyright 2009 Elsevier B.V. All rights reserved.

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. 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.

  3. [Clinical Value of Serum Fructosamine Measurement in IgA Type Multiple Myeloma].

    Science.gov (United States)

    Zhang, Jing-Yu; Fan, Hong; Chen, Li-Xin; Wang, Li-Fang; Wang, Hong-Fei; Shi, Hai-Xiang

    2017-04-01

    To investigate the value of serum fructosamine (FMN) measurement in clinical typing and staging of multiple myeloma(MM) as well as evaluation of curative efficacy and prognosis of IgA type MM. The levels of FMN were detected by nitro-blue-tetrazolium colorimetric method in 62 IgA type MM patients, 65 IgG type MM patients, 24 IgM type MM patients. The difference between the serum FMN levels and different MM types and its relationship with IgA type MM, patients' stages, efficacy and as well as, the effect of FMN level on overall survival (OS) time of IgA type MM patients were analyzed. FMN level of IgA type patients was obviously higher than that of IgG type and IgM type patients. Patients of DS stage III had higher FMN level than that of stage II, and patients of DS stage II had higher FMN level than that of stage I, the differences were statistical significant(P<0.05). Patients of ISS stage III also had higher FMN level than that of stage II, and patients of ISS stage II also had higher FMN level than that of stage I, the differences were statistical significant(P<0.05). After treatment, FMN level of patients obtained complete remission (CR) or very good partial remission(VGPR) obviously decreased, FMN level of patients obtained partial remission(PR) decreased, FMN level of patients obtained less than PR increased. Patients with normal FMN level had longer OS time, while patients with high FMN level had obviously short OS time. Serum FMN is obviously elevated in the IgA type MM, there is a certain association between staging and serum FMN level, the IgA type MM patients with FMN normalization after treatment have better prognosis.

  4. Butyrylcholinesterase activity in Nigerian type 2 diabetics with and ...

    African Journals Online (AJOL)

    ... -cells lose their ability to compensate for the prevailing levels of insulin sensitivity. ... Butyrylcholinesterase activity in diabetes and metabolic syndrome is ... obese type 2 diabetics without metabolic syndrome (n = 21) and non-obese type 2 ...

  5. Multiple pharmacy use and types of pharmacies used to obtain prescriptions.

    Science.gov (United States)

    Look, Kevin A; Mott, David A

    2013-01-01

    To evaluate trends and patterns in the prevalence of multiple pharmacy use (MPU) and to describe the number and types of pharmacies used by multiple pharmacy users from 2003 to 2009. Retrospective, cross-sectional, descriptive study. United States from 2003 to 2009. 89,941 responses to the Medical Expenditure Panel Survey over 7 years. Analysis of respondent pharmacy use behaviors. Annual use of more than one pharmacy and number and types of pharmacies used. MPU among patients using medications increased significantly during the study period (from 36.4% [95% CI 35.2-37.6] in 2003 to 43.2% [41.9-44.4] in 2009)-a relative increase of 18.7% ( P = 0.01). Multiple pharmacy users used between 2 and 17 different pharmacies per year to obtain prescription medications. Although approximately 70% of multiple pharmacy users used only two pharmacies, the proportion using three or more pharmacies increased from 24.1% (22.5-25.7) in 2003 to 29.1% (27.4-30.8) in 2009. Mail service pharmacy use had the largest relative increase among multiple pharmacy users during the study period (27.2%), and MPU was nearly twice as high (75%) among mail service users compared with non-mail service users. MPU is common on a national level and has increased greatly in recent years. Patient use of pharmacies that have the potential to share medication information electronically is low among multiple pharmacy users, suggesting increased workload for pharmacists and potential medication safety concerns. This has important implications for pharmacists, as it potentially impedes their ability to maintain accurate medication profiles for patients.

  6. 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).

  7. 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.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Microfluidic assay for simultaneous culture of multiple cell types on surfaces or within hydrogels

    Science.gov (United States)

    Shin, Yoojin; Han, Sewoon; Jeon, Jessie S.; Yamamoto, Kyoko; Zervantonakis, Ioannis K.; Sudo, Ryo; Kamm, Roger D.; Chung, Seok

    2014-01-01

    This protocol describes a simple but robust microfluidic assay combining three-dimensional (3D) and two-dimensional (2D) cell culture. The microfluidic platform comprises hydrogel incorporating chambers between surface-accessible microchannels. Using this platform, well-defined biochemical and biophysical stimuli can be applied to multiple cell types interacting over distances of experiments can run for up to several weeks. PMID:22678430

  13. Recommendations for Evaluating Multiple Filters in Ballast Water Management Systems for US Type Approval

    Science.gov (United States)

    2016-01-01

    water options are summarized in Table 5. Additionally, NIOZ offers BWMS vendors the option to experiment using the NIOZ facility prior to setting up... supply volume and pressure requirements Fresh water requirements Volume and flow requirements for fresh water supply Electrical supply requirements...Recommendations for Evaluating Multiple Filters in Ballast Water Management Systems for US Type Approval Lisa A. Drake1, Timothy P. Wier2, Evan

  14. 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.

  15. 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.

  16. 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...

  17. 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...

  18. 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.

  19. Identifying and quantifying dependencies between time-lagged risks of multiple types

    Science.gov (United States)

    Hillier, John K.

    2017-04-01

    Multiple types of hazard exist (e.g. earthquake, flood, snow), each potentially causing risk. These may be linked, dependent, or interact. Comparing 'events' of different types, however is non-trivial as their extent (e.g. tsunami after earthquake or storm surge during winter storms) (A&B together), iii) cascades and hazard chains (e.g. A->B->C), or iv) mutually underlying cause (i.e. C influences types A and B). This talk will consider how to identify, quantify, and start to understand dependencies between time-lagged risks of multiple types in the context of this last type of interaction, although the methods used may be more generally applicable. Particularly useful are loss data (e.g. £, time, lives), which implicitly make hazards comparable [1], and a number of statistical methods that have been adapted for multi-hazard purposes. Interactions can modify losses with respect to an assumption of independence by (i.e. >£0.3 billion, 26%), be identified in short time-series (10-15 yrs), and give at least some additional insights into physical processes. [1] Hillier, J. K., Macdonald, N., Leckebusch, G., Stavrinides (2015) Interactions between apparently primary weather-driven hazards and their cost. Env. Res. Lett. 10, 104003, doi:10.1088/1748-9326/10/10/104003

  20. Money Management Activities in Persons With Multiple Sclerosis.

    Science.gov (United States)

    Goverover, Yael; Haas, Shannon; DeLuca, John

    2016-11-01

    To examine whether participants with multiple sclerosis (MS) have more problems in managing finances compared with persons without MS, and to examine the variables that may contribute to these problems. A cross-sectional study. Nonprofit rehabilitation research institution and the community. Participants (N=53) comprised adults with MS (n=30) and persons without MS (n=23) who were recruited from a nonprofit rehabilitation research institution and from the community. Not applicable. Participants were administered a battery of neuropsychological tests, a money management survey, and a functional test to assess money management skills. Individuals with MS reported and demonstrated more problems managing money than persons without MS. Impaired cognitive functioning was significantly correlated with difficulties in money management. Self-report of functional status (Functional Behavior Profile) was significantly correlated with self-reported money management skills. To our knowledge, this is the first study to examine money management in MS. Money management is an important activity of daily living that presents problems for individuals with MS. Managing one's own money requires adequate processing speed abilities as well as executive-attentional abilities. Additional studies are needed to explore this area and understand the nature of the problem. Copyright © 2016 American Congress of Rehabilitation Medicine. Published by Elsevier Inc. All rights reserved.

  1. Promiscuous Mutations Activate the Non-Canonical NF-kB Pathway in Multiple Myeloma

    OpenAIRE

    Keats, Jonathan J.; Fonseca, Rafael; Chesi, Marta; Schop, Roelandt; Baker, Angela; Chng, Wee-Joo; Van Wier, Scott; Tiedemann, Rodger; Shi, Chang-Xin; Sebag, Michael; Braggio, Esteban; Henry, Travis; Zhu, Yuan-Xiao; Fogle, Homer; Price-Troska, Tammy

    2007-01-01

    Activation of NF-kB has been noted in many tumor types, however only rarely has this been linked to an underlying genetic mutation. An integrated analysis of high-density oligonucleotide array CGH and gene expression profiling data from 155 multiple myeloma samples identified a promiscuous array of abnormalities contributing to the dysregulation of NF-kB in approximately 20% of patients. We report mutations in ten genes causing the inactivation of TRAF2, TRAF3, CYLD, cIAP1/cIAP2, and activati...

  2. Novel visible light activated type 1 photosensitizers

    Science.gov (United States)

    Rajagopalan, Raghavan; Karwa, Amolkumar; Poreddy, Amruta R.; Lusiak, Przemyslaw M.; Pandurangi, Raghoottama S.; Cantrell, Gary L.; Dorshow, Richard B.

    2010-02-01

    Photodynamic therapy of tumors involving Type 2 photosenstizers has been conspicuously successful, but the Type 1 process, in contrast, has not received much attention despite its considerable potential. Accordingly, several classes of molecules containing fragile bonds such as azido (-N=N=N), azo (-N=N-), and oxaza (-N-O-) functional groups that produce reactive intermediates such as radicals and nitrenes upon photoexcitation with visible light were prepared and tested for cell viability using U397 leukemia cell line. The cells were incubated with the photosensitizer at various concentrations, and were illuminated for 5, 10, and 20 minutes. The results show that all the photosensitizers caused cell death compared to the controls when exposed to both the photosensitizers and light.

  3. 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.

  4. Gazing and Typing Activities during Translation

    DEFF Research Database (Denmark)

    Carl, Michael; Kay, Martin

    2011-01-01

    The paper investigates the notion of Translation Units (TUs) from a cognitive angle. A TU is defined as the translator’s focus of attention at a time. Since attention can be directed towards source text (ST) understanding and/or target text (TT) production, we analyze the activity data of the tra...

  5. 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

  6. Differences in typing forces, muscle activity, comfort, and typing performance among virtual, notebook, and desktop keyboards.

    Science.gov (United States)

    Kim, Jeong Ho; Aulck, Lovenoor; Bartha, Michael C; Harper, Christy A; Johnson, Peter W

    2014-11-01

    The present study investigated whether there were physical exposure and typing productivity differences between a virtual keyboard with no tactile feedback and two conventional keyboards where key travel and tactile feedback are provided by mechanical switches under the keys. The key size and layout were same across all the keyboards. Typing forces; finger and shoulder muscle activity; self-reported comfort; and typing productivity were measured from 19 subjects while typing on a virtual (0 mm key travel), notebook (1.8 mm key travel), and desktop keyboard (4 mm key travel). When typing on the virtual keyboard, subjects typed with less force (p's typing forces and finger muscle activity came at the expense of a 60% reduction in typing productivity (p typing sessions or when typing productivity is at a premium, conventional keyboards with tactile feedback may be more suitable interface.

  7. 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.

  8. 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.

  9. 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.

  10. Klinefelter's Syndrome with Seizure, Pseudohypoparathyroidism Type Ib and Multiple Endocrine Dysfunctions

    Directory of Open Access Journals (Sweden)

    Chwen-Yi Yang

    2005-12-01

    Full Text Available Klinefelter's syndrome is rarely associated with hypocalcemia, especially pseudohypoparathyroidism (PHP type Ib. We describe a case of Klinefelter's syndrome associated with seizure, PHP type Ib and multiple endocrine dysfunctions. A 19-year-old Taiwanese male was admitted due to seizures with loss of consciousness. He had been diagnosed with Klinefelter's syndrome with seizure disorder and hypocalcemia 3 months previously. Physical examination revealed eunuchoidism but no osteodystrophy, while laboratory data revealed severe hypocalcemia, hyperphosphatemia, and elevated parathyroid hormone. Chromosomal study showed 47, XXY. Osteoporosis was found on chest and abdominal radiography. Dense calcification in the cerebrum and cerebellum was shown on brain computed tomography and magnetic resonance imaging. Elevation of the patient's serum calcium level was noted after vitamin D and calcium carbonate supplements were given. Klinefelter's syndrome is rarely associated with PHP type Ib; our patient's hypocalcemia improved after long-term aggressive treatment.

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. 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.

  16. Multiple intracranial aneurysms and moyamoya disease associated with microcephalic osteodysplastic primordial dwarfism type II: surgical considerations.

    Science.gov (United States)

    Waldron, James S; Hetts, Steven W; Armstrong-Wells, Jennifer; Dowd, Christopher F; Fullerton, Heather J; Gupta, Nalin; Lawton, Michael T

    2009-11-01

    Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a rare genetic syndrome characterized by extremely small stature and microcephaly, and is associated in 25% of patients with intracranial aneurysms and moyamoya disease. Although aneurysmal subarachnoid hemorrhage and stroke are leading causes of morbidity and death in these patients, MOPD II is rarely examined in the neurosurgical literature. The authors report their experience with 3 patients who presented with MOPD II, which includes a patient with 8 aneurysms (the most aneurysms reported in the literature), and the first report of a patient with both moyamoya disease and multiple aneurysms. The poor natural history of these lesions indicates aggressive microsurgical and/or endovascular therapy. Microsurgery, whether for aneurysm clip placement or extracranial-intracranial bypass, is challenging due to tight surgical corridors and diminutive arteries in these patients, but is technically feasible and strongly indicated when multiple aneurysms must be treated or cerebral revascularization is needed.

  17. 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.

  18. Pancreatic-type Acinar Cell Carcinoma of the Stomach Included in Multiple Primary Carcinomas.

    Science.gov (United States)

    Yonenaga, Yoshikuni; Kurosawa, Manabu; Mise, Masahiro; Yamagishi, Miki; Higashide, Shunichi

    2016-06-01

    Pancreatic-type acinar cell carcinoma (ACC) in the stomach is extraordinarily rare. We pathologically examined two cases with multiple primary carcinomas, including gastric tumors. Gastric cancer specimens were examined by immunostaining and electron microscopy. Both cases had cancer cells with acinar patterns, resembling pancreatic ACC. The cancer cells in the first case were positive for exocrine markers, including chymotrypsin, lipase and alpha-1 antichymotrypsin (ACT), as well as neuroendocrine markers, including chromogranin A and synaptophysin. The cancer cells in the second case were positive for chymotrypsin and alpha-1 ACT, while being slightly positive for chromogranin A and synaptophysin. Ultrastructurally, cancer cells contained zymogen granules in both cases. The final diagnosis was pancreatic mixed acinar-neuroendocrine carcinoma and pure pancreatic ACC, respectively. We confirmed two cases with gastric pancreatic-type ACC included in multiple primary carcinomas. This type of double cancer has not been reported previously. Copyright© 2016 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

  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. 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], ...

  1. 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...

  2. 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.

  3. 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.

  4. A feature selection method based on multiple kernel learning with expression profiles of different types.

    Science.gov (United States)

    Du, Wei; Cao, Zhongbo; Song, Tianci; Li, Ying; Liang, Yanchun

    2017-01-01

    With the development of high-throughput technology, the researchers can acquire large number of expression data with different types from several public databases. Because most of these data have small number of samples and hundreds or thousands features, how to extract informative features from expression data effectively and robustly using feature selection technique is challenging and crucial. So far, a mass of many feature selection approaches have been proposed and applied to analyse expression data of different types. However, most of these methods only are limited to measure the performances on one single type of expression data by accuracy or error rate of classification. In this article, we propose a hybrid feature selection method based on Multiple Kernel Learning (MKL) and evaluate the performance on expression datasets of different types. Firstly, the relevance between features and classifying samples is measured by using the optimizing function of MKL. In this step, an iterative gradient descent process is used to perform the optimization both on the parameters of Support Vector Machine (SVM) and kernel confidence. Then, a set of relevant features is selected by sorting the optimizing function of each feature. Furthermore, we apply an embedded scheme of forward selection to detect the compact feature subsets from the relevant feature set. We not only compare the classification accuracy with other methods, but also compare the stability, similarity and consistency of different algorithms. The proposed method has a satisfactory capability of feature selection for analysing expression datasets of different types using different performance measurements.

  5. Circadian Rest-Activity Rhythm in Pediatric Type 1 Narcolepsy.

    Science.gov (United States)

    Filardi, Marco; Pizza, Fabio; Bruni, Oliviero; Natale, Vincenzo; Plazzi, Giuseppe

    2016-06-01

    Pediatric type 1 narcolepsy is often challenging to diagnose and remains largely undiagnosed. Excessive daytime sleepiness, disrupted nocturnal sleep, and a peculiar phenotype of cataplexy are the prominent features. The knowledge available about the regulation of circadian rhythms in affected children is scarce. This study compared circadian rest-activity rhythm and actigraphic estimated sleep measures of children with type 1 narcolepsy versus healthy controls. Twenty-two drug-naïve type 1 narcolepsy children and 21 age- and sex- matched controls were monitored for seven days during the school week by actigraphy. Circadian activity rhythms were analyzed through functional linear modeling; nocturnal and diurnal sleep measures were estimated from activity using a validated algorithm. Children with type 1 narcolepsy presented an altered rest-activity rhythm characterized by enhanced motor activity throughout the night and blunted activity in the first afternoon. No difference was found between children with type 1 narcolepsy and controls in the timing of the circadian phase. Actigraphic sleep measures showed good discriminant capabilities in assessing type 1 narcolepsy nycthemeral disruption. Actigraphy reliably renders the nycthemeral disruption typical of narcolepsy type 1 in drug-naïve children with recent disease onset, indicating the sensibility of actigraphic assessment in the diagnostic work-up of childhood narcolepsy type 1. © 2016 Associated Professional Sleep Societies, LLC.

  6. 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.

  7. Assisting Persons with Multiple Disabilities to Move through Simple Occupational Activities with Automatic Prompting

    Science.gov (United States)

    Lancioni, Giulio E.; Singh, Nirbhay N.; O'Reilly, Mark F.; Sigafoos, Jeff; Oliva, Doretta; Campodonico, Francesca; Groeneweg, Jop

    2008-01-01

    The present study assessed the possibility of assisting four persons with multiple disabilities to move through and perform simple occupational activities arranged within a room with the help of automatic prompting. The study involved two multiple probe designs across participants. The first multiple probe concerned the two participants with…

  8. Multiple endocrine neoplasia type II B with symptoms suggesting Hirschsprung's disease: a case report.

    Science.gov (United States)

    Mahaffey, S M; Martin, L W; McAdams, A J; Ryckman, F C; Torres, M

    1990-01-01

    A 3-year-old child was referred with a tentative diagnosis of Hirschsprung's disease because of life-long constipation and "megacolon" demonstrated radiographically. Our rectal biopsy revealed hyperganglionosis suggestive of multiple endocrine neoplasia (MEN) type II B. This, in addition to an elevated serum calcitonin level, prompted surgical removal of her thyroid, which appeared grossly normal but on sectioning, contained a medullary carcinoma in each lobe. She remains disease-free 5 years later. Gastrointestinal symptoms are a significant component of the MEN type II B syndrome, and often antedate the full phenotypic expression of the syndrome and the development of potentially lethal endocrine neoplasms. On the basis of this experience, it is recommended that MEN II B be included in the differential diagnosis of chronic constipation.

  9. 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.

  10. 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.

  11. Diagnosis and Management of Multiple Endocrine Neoplasia Type 1 (MEN1

    Directory of Open Access Journals (Sweden)

    Dreijerink Koen MA

    2005-02-01

    Full Text Available Abstract Multiple endocrine neoplasia type 1 (MEN1 is an autosomal dominantly inherited disorder, characterised by the occurrence of tumours of the parathyroid glands, the pancreatic islets, the pituitary gland, the adrenal glands and neuroendocrine carcinoid tumours. Carcinoid tumours of the thymus and pancreatic-duodenal gastrinomas are the most harmful tumour types, since these tumours have malignant potential and curative treatment is difficult to achieve. MEN1 is caused by germline mutations of the MEN1 tumour suppressor gene. Mutation analysis enables mutation carriers to be identified. MEN1 patients and their family members, family members of mutation carriers and patients who are clinically suspected to be carriers of a MEN1 gene mutation are eligible for mutation analysis. MEN1-associated tumours can be detected and treated at an early stage through periodical clinical monitoring of mutation carriers.

  12. 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.

  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. 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

  15. 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

  16. 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.

  17. 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.

  18. The Parietal Cortex in Sensemaking: The Dissociation of Multiple Types of Spatial Information

    Directory of Open Access Journals (Sweden)

    Yanlong Sun

    2013-01-01

    Full Text Available 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.

  19. 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.

  20. Severe hypernatremia and hyperchloremia in an elderly patient with IgG-kappa-type multiple myeloma

    Directory of Open Access Journals (Sweden)

    Imashuku S

    2013-05-01

    Full Text Available Shinsaku Imashuku, Naoko Kudo, Kagekatsu KuboDivision of Hematology, Takasago-seibu Hospital, Takasago, JapanAbstract: A 77-year-old male was admitted to hospital after suffering a pelvic bone fracture in a road traffic accident and was incidentally found to have IgG-kappa-type multiple myeloma with hypercalcemia. The patient was also noted to be hypokalemic and had low HCO3-, with possible damage to the distal tubules in the kidneys. When the treatment was begun with bortezomib/dexamethasone/elcatonin and sodium bicarbonate (NaHCO3 in normal saline (equivalent to a daily sodium dose of 200 millimoles per liter [mmol/L], the patient was in a state of poor oral fluid intake. The patient developed hypernatremia and hyperchloremia, with a peak serum sodium and chloride levels of 183 mmol/L and 153 mmol/L, respectively, at the sixth day after the start of treatment. Following the switch of the intravenous infusions from normal saline to soldem 1 and soldem 3 solutions, these high-electrolyte levels gradually returned to normal over the next 7 days. Although the patient showed disturbed consciousness (Japan Coma Scale = JCS-I-3 during the period of electrolyte abnormality, he eventually fully recovered without sequelae. In this patient, we successfully managed the severe hypernatremia/hyperchloremia, caused by the combined effects of intravenous saline burden in a state of poor oral fluid intake, during the treatment for IgG-kappa type multiple myeloma.Keywords: hypernatremia, hyperchloremia, multiple myeloma, IgG-kappa, metabolic acidosis, renal tubular damage

  1. 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

  2. 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.

  3. 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...

  4. 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.

  5. 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

  6. 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...

  7. 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.

  8. 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.

  9. 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 for the worry of being diagnosed with a cancer susceptibility syndrome....

  10. 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....

  11. 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

  12. 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.

  13. 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.

  14. 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.

  15. Effects of cumulus entrainment and multiple cloud types on a January global climate model simulation

    Science.gov (United States)

    Yao, Mao-Sung; Del Genio, Anthony D.

    1989-01-01

    An improved version of the GISS Model II cumulus parameterization designed for long-term climate integrations is used to study the effects of entrainment and multiple cloud types on the January climate simulation. Instead of prescribing convective mass as a fixed fraction of the cloud base grid-box mass, it is calculated based on the closure assumption that the cumulus convection restores the atmosphere to a neutral moist convective state at cloud base. This change alone significantly improves the distribution of precipitation, convective mass exchanges, and frequencies in the January climate. The vertical structure of the tropical atmosphere exhibits quasi-equilibrium behavior when this closure is used, even though there is no explicit constraint applied above cloud base.

  16. Multiple endocrine neoplasias type 2A and thyroid medullary carcinoma: an interdisciplinary challenge.

    Science.gov (United States)

    Haecker, Frank-Martin; Oertli, Daniel; Gissler, Stefanie; Zumsteg, Urs; Avoledo, Pierino; von Schweinitz, Dietrich

    2003-04-01

    The diagnosis and treatment of multiple endocrine neoplasias type 2A (MEN 2A) requires interdisciplinary management. The association of RET proto-oncogene mutations and medullary thyroid carcinoma (MTC) in children is well-known, but the optimal timing for elective surgery is controversial. Besides the risk of MTC, associated anomalies like hyperparathyroidism have to be considered. We report the results of molecular genetic investigations, the pentagastrin stimulation test, pre- and postoperative staging, and histologic examinations of four children who had a positive family history for MEN 2A. Histologic specimens of the removed thyroid glands showed MTC in all four cases. The patients had an uneventful postoperative clinical course. In view of the recent literature and our patients' results, we suggest a concept for diagnostic strategy and timing of the elective thyroidectomy.

  17. Multiple endocrine neoplasia type 1 with upper gastrointestinal hemorrhage and perforation: a case report and review.

    Science.gov (United States)

    Lu, Ying-Ying; Zhu, Feng; Jing, Da-Dao; Wu, Xie-Ning; Lu, Lun-Gen; Zhou, Gen-Quan; Wang, Xing-Peng

    2013-02-28

    Multiple endocrine neoplasia type 1 (MEN1) is a rare hereditary syndrome known to predispose subjects to endocrine neoplasms in a variety of tissues such as the parathyroid glands, pituitary gland, pancreas and gastrointestinal tract. We herein report a patient with a past history of pituitary adenoma, presenting with symptoms of chronic diarrhea for nearly one year and a sudden upper gastrointestinal hemorrhage as well as perforation without signs. Nodules in the duodenum and in the uncinate process and tail of pancreas and enlargement of the parathyroid glands were detected on preoperative imaging. Gastroscopy revealed significant ulceration and esophageal reflux diseases. The patient underwent subtotal parathyroidectomy and autotransplantation, pylorus-preserving pancreaticoduodenectomy and pancreatic tail resection and recovered well. The results observed in our patient suggest that perforation and bleeding of intestine might be symptoms of Zollinger-Ellison Syndrome in patients with MEN1.

  18. 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

  19. 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.

  20. 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......) patients who recently have been reported to be PCR-positive for HTLV-I gag and env sequences, and eight healthy individuals. Precautions were taken in order to reduce the risk of cross-contamination in the PCR. In the two TSP patients strong signals were obtained with gag, env and pol amplification primers...... data do not confirm the presence of HTLV-I sequences in MS patients....

  1. 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.

  2. 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.

  3. Complex dynamics in the Leslie-Gower type of the food chain system with multiple delays

    Science.gov (United States)

    Guo, Lei; Song, Zi-Gen; Xu, Jian

    2014-08-01

    In this paper, we present a Leslie-Gower type of food chain system composed of three species, which are resource, consumer, and predator, respectively. The digestion time delays corresponding to consumer-eat-resource and predator-eat-consumer are introduced for more realistic consideration. It is called the resource digestion delay (RDD) and consumer digestion delay (CDD) for simplicity. Analyzing the corresponding characteristic equation, the stabilities of the boundary and interior equilibrium points are studied. The food chain system exhibits the species coexistence for the small values of digestion delays. Large RDD/CDD may destabilize the species coexistence and induce the system dynamic into recurrent bloom or system collapse. Further, the present of multiple delays can control species population into the stable coexistence. To investigate the effect of time delays on the recurrent bloom of species population, the Hopf bifurcation and periodic solution are investigated in detail in terms of the central manifold reduction and normal form method. Finally, numerical simulations are performed to display some complex dynamics, which include multiple periodic solution and chaos motion for the different values of system parameters. The system dynamic behavior evolves into the chaos motion by employing the period-doubling bifurcation.

  4. 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.

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

    DEFF Research Database (Denmark)

    Broholm, H; Andersen, B; Wanscher, B

    2004-01-01

    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...

  6. [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.

  7. 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

  8. 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).

  9. 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.

  10. 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.

  11. 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 ...

  12. Exploring types of focused factories in hospital care: a multiple case study.

    Science.gov (United States)

    Bredenhoff, Eelco; van Lent, Wineke A M; van Harten, Wim H

    2010-06-07

    Focusing on specific treatments or diseases is proposed as a way to increase the efficiency of hospital care. The definition of "focus" or "focused factory", however, lacks clarity. Examples in health care literature relate to very different organizations.Our aim was to explore the application of the focused factory concept in hospital care, including an indication of its performance, resulting in a conceptual framework that can be helpful in further identifying different types of focused factories. Thus contributing to the understanding of the diversity of examples found in the literature. We conducted a cross-case comparison of four multiple-case studies into hospital care. To cover a broad array of focus, different specialty fields were selected. Each study investigated the organizational context, the degree of focus, and the operational performance. Focus was measured using an instrument translated from industry. Data were collected using both qualitative and quantitative methods and included site visits. A descriptive analysis was performed at the case study and cross-case studies level. The operational performance per specialty field varied considerably, even when cases showed comparable degrees of focus. Cross-case comparison showed three focus domains. The product domain considered specialty based focused factories that treated patients for a single-specialty, but did not pursue a specific strategy nor adapted work-designs or layouts. The process domain considered delivery based focused factories that treated multiple groups of patients and often pursued strategies to improve efficiency and timeliness and adapted work-designs and physical layouts to minimize delays. The product-process domain considered procedure based focused factories that treated a single well-defined group of patients offering one type of treatment. The strategic focusing decisions and the design of the care delivery system appeared especially important for delivery and procedure based

  13. Exploring types of focused factories in hospital care: a multiple case study

    Directory of Open Access Journals (Sweden)

    van Lent Wineke AM

    2010-06-01

    Full Text Available Abstract Background Focusing on specific treatments or diseases is proposed as a way to increase the efficiency of hospital care. The definition of "focus" or "focused factory", however, lacks clarity. Examples in health care literature relate to very different organizations. Our aim was to explore the application of the focused factory concept in hospital care, including an indication of its performance, resulting in a conceptual framework that can be helpful in further identifying different types of focused factories. Thus contributing to the understanding of the diversity of examples found in the literature. Methods We conducted a cross-case comparison of four multiple-case studies into hospital care. To cover a broad array of focus, different specialty fields were selected. Each study investigated the organizational context, the degree of focus, and the operational performance. Focus was measured using an instrument translated from industry. Data were collected using both qualitative and quantitative methods and included site visits. A descriptive analysis was performed at the case study and cross-case studies level. Results The operational performance per specialty field varied considerably, even when cases showed comparable degrees of focus. Cross-case comparison showed three focus domains. The product domain considered specialty based focused factories that treated patients for a single-specialty, but did not pursue a specific strategy nor adapted work-designs or layouts. The process domain considered delivery based focused factories that treated multiple groups of patients and often pursued strategies to improve efficiency and timeliness and adapted work-designs and physical layouts to minimize delays. The product-process domain considered procedure based focused factories that treated a single well-defined group of patients offering one type of treatment. The strategic focusing decisions and the design of the care delivery system

  14. 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...

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. 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.

  1. 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

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

    Institute of Scientific and Technical Information of China (English)

    Hidetaka; Hamasaki[1

    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-exerciseactivity 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. 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...

  4. Disease and treatment factors associated with lower quality of life scores in adults with multiple endocrine neoplasia type I.

    Science.gov (United States)

    Goswami, Sneha; Peipert, Benjamin J; Helenowski, Irene; Yount, Susan E; Sturgeon, Cord

    2017-09-14

    Physical and psychosocial morbidity of multiple endocrine neoplasia type-1 is ill-defined. How disease and treatment-related factors relate to patient-reported outcomes including health-related quality of life is unknown. We hypothesized that disease and treatment burden negatively impacts health-related quality of life in adults with multiple endocrine neoplasia type-1. Adults (≥18 years) with multiple endocrine neoplasia type-1 completed an online survey of demographics, disease features, treatments, and Patient-Reported Outcomes Measurement Information System 29-item profile measure, and scores were compared with normative US data. Multivariable modeling was performed to evaluate factors associated with decreased health-related quality of life. Multiple endocrine neoplasia type-1 patients (n = 207) reported worse health-related quality of life compared with US normative data in all health-related quality of life domains (P 50 miles for doctor appointments and ≥20 doctor appointments/year (P < .05) were associated with worse health-related quality of life. History of pancreatic neuroendocrine tumors was not associated with worse health-related quality of life. This is the largest study to assess clinical and treatment factors associated with health-related quality of life in multiple endocrine neoplasia type-1. Persistent hyperparathyroidism, increased travel distance and frequency of doctor appointments were all associated with worse health-related quality of life. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. 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)

  6. Day Services for People With Profound Intellectual and Multiple Disabilities : An Analysis of Thematically Organized Activities

    NARCIS (Netherlands)

    van der Putten, Annette; Vlaskamp, Carla

    One of the recent ideas to emerge in the Netherlands for improving the quality of activities provided for people with profound intellectual and multiple disabilities is to organize these activities thematically. Among the expected effects was that more activities with a greater variety would be

  7. Heart rate and physical activity patterns in persons with profound intellectual and multiple disabilities.

    NARCIS (Netherlands)

    Waninge, A.; Putten, A.A. van der; Stewart, R.E.; Steenbergen, B.; Wijck, R. van; Schans, C.P. van der

    2013-01-01

    Because physical fitness and health are related to physical activity, it is important to gain an insight into the physical activity levels of persons with profound intellectual and multiple disabilities (PIMD). The purpose of this study was to examine heart rate patterns to measure the activity

  8. Heart rate and physical activity patterns in persons with profound intellectual and multiple disabilities

    NARCIS (Netherlands)

    Waninge, A.; Putten, A.A.J. van der; Stewart, R.E.; Steenbergen, B.; Wijck, R. van; Schans, C.P. van der

    2013-01-01

    Because physical fitness and health are related to physical activity, it is important to gain an insight into the physical activity levels of persons with profound intellectual and multiple disabilities (PIMD). The purpose of this study was to examine heart rate patterns to measure the activity

  9. 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.

  10. 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.

  11. 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. PMID:22761887

  12. 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...

  13. 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.

  14. 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)

  15. Perioperative outcomes of syndromic paraganglioma and pheochromocytoma resection in patients with von Hippel-Lindau disease, multiple endocrine neoplasia type 2, or neurofibromatosis type 1.

    Science.gov (United States)

    Butz, James J; Yan, Qi; McKenzie, Travis J; Weingarten, Toby N; Cavalcante, Alexandre N; Bancos, Irina; Young, William F; Schroeder, Darrell R; Martin, David P; Sprung, Juraj

    2017-09-14

    Pheochromocytoma and/or paraganglioma associated with neurofibromatosis type 1, multiple endocrine neoplasia type 2A, and von Hippel-Lindau disease have different catecholamine biochemical phenotypes. We examined perioperative outcomes of pheochromocytoma/paraganglioma resection in 3 syndromic forms. Retrospective review of patients undergoing resection of syndromic pheochromocytoma/paraganglioma from 2000 through 2016. Eighty-one patients underwent pheochromocytoma/paraganglioma resection (multiple endocrine neoplasia type 2A, n = 36; neurofibromatosis type 1, n = 26; von Hippel-Lindau disease, n = 19). Tumor size differed across groups; patients with neurofibromatosis type 1 and von Hippel-Lindau disease had the largest tumors (P = .017). Larger tumor volumes correlated with higher urine 24-hour total metanephrine (r = 0.94, P < .001; r = 0.67, P = .033; and r = 0.89, P < .001 for multiple endocrine neoplasia type 2A, von Hippel-Lindau disease, and neurofibromatosis type 1, respectively). High adrenergic secretion (24-hour urine metanepinephrine) was found in neurofibromatosis type 1 (median, 861 μg/24 h), similar to that found in multiple endocrine neoplasia type 2A (median, 809 μg/24 h). The highest noradrenergic secretion (24-hour urine normetanephrine) occurred with von Hippel-Lindau disease (median, 4,598 μg/24 h), followed by neurofibromatosis type 1 and multiple endocrine neoplasia type 2A (median, 1,607 and 923 μg/24 h, respectively). The highest graded complications occurred among patients with neurofibromatosis type 1 (P = .036). However, when comparing postoperative outcomes across 3 groups in those who had laparoscopic resection, there was no significant difference (P = .955). Patients with neurofibromatosis type 1 had the most volatile intraoperative hemodynamic course and more severe postoperative complications. These complications are related to large tumors associated with abundant catecholamine secretion and the fact that a high

  16. 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

  17. 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.

  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. 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.)

  20. 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

  1. Coexistence and local μ-stability of multiple equilibrium points for memristive neural networks with nonmonotonic piecewise linear activation functions and unbounded time-varying delays.

    Science.gov (United States)

    Nie, Xiaobing; Zheng, Wei Xing; Cao, Jinde

    2016-12-01

    In this paper, the coexistence and dynamical behaviors of multiple equilibrium points are discussed for a class of memristive neural networks (MNNs) with unbounded time-varying delays and nonmonotonic piecewise linear activation functions. By means of the fixed point theorem, nonsmooth analysis theory and rigorous mathematical analysis, it is proven that under some conditions, such n-neuron MNNs can have 5(n) equilibrium points located in ℜ(n), and 3(n) of them are locally μ-stable. As a direct application, some criteria are also obtained on the multiple exponential stability, multiple power stability, multiple log-stability and multiple log-log-stability. All these results reveal that the addressed neural networks with activation functions introduced in this paper can generate greater storage capacity than the ones with Mexican-hat-type activation function. Numerical simulations are presented to substantiate the theoretical results. Copyright © 2016 Elsevier Ltd. All rights reserved.

  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. 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.

  4. 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.

  5. Towards a human-on-chip: culturing multiple cell types on a chip with compartmentalized microenvironments.

    Science.gov (United States)

    Zhang, Chi; Zhao, Ziqing; Abdul Rahim, Nur Aida; van Noort, Danny; Yu, Hanry

    2009-11-21

    We have developed a multi-channel 3D microfluidic cell culture system (multi-channel 3D-microFCCS) with compartmentalized microenvironments for potential application in human drug screening. To this end, the multi-channel 3D-microFCCS was designed for culturing different 3D cellular aggregates simultaneously to mimic multiple organs in the body. Four human cell types (C3A, A549, HK-2 and HPA) were chosen to represent the liver, lung, kidney and the adipose tissue, respectively. Cellular functions were optimized by supplementing the common medium with growth factors. However, TGF-beta1 was found to enhance A549 functions but inhibit C3A functions. Therefore, TGF-beta1 was specifically controlled-released inside the A549 compartment by means of gelatin microspheres mixed with cells, thus creating a cell-specific microenvironment. The function of A549 cells was enhanced while the functions of C3A, HK-2 and HPA cells were uncompromised, demonstrating the limited cross-talk between cell culture compartments similar to the in vivo situation. Such a multi-channel 3D-microFCCS could be potentially used to supplement or even replace animal models in drug screening.

  6. Results of initial operation for hyperparathyroidism in patients with multiple endocrine neoplasia type 1.

    Science.gov (United States)

    Elaraj, Dina M; Skarulis, Monica C; Libutti, Steven K; Norton, Jeffrey A; Bartlett, David L; Pingpank, James F; Gibril, Fathia; Weinstein, Lee S; Jensen, Robert T; Marx, Stephen J; Alexander, H Richard

    2003-12-01

    Hyperparathyroidism in patients with multiple endocrine neoplasia type 1 (MEN1) is characterized by multiglandular disease and a propensity for recurrence after parathyroidectomy (PTx). This study analyzes outcomes of a cohort of MEN1 patients undergoing initial PTx at one institution. Between April 1960 and September 2002, 92 patients with MEN1 underwent initial PTx. Outcomes were analyzed based on extent of parathyroid resection. Fourteen percent had 2.5 or fewer glands resected, 69% had subtotal PTx, and 17% had total PTx (88% with immediate autotransplantation). The initial surgical cure rate was 98%. Excluding 6 patients lost to follow-up, 33% have developed recurrent hyperparathyroidism (in 46% after < or =2.5 PTx, in 33% after subtotal, and in 23% after total PTx). Median recurrence-free survival was not statistically significantly different between subtotal versus total PTx, but it was longer for subtotal and total PTx compared with lesser resection (16.5 vs 7.0 years, respectively, P=.03). The incidence of severe hypoparathyroidism was 46% after total versus 26% after subtotal PTx. Subtotal and total PTx result in durable control of MEN1-associated hyperparathyroidism and have longer recurrence-free intervals compared with lesser resection. The high incidence of severe hypoparathyroidism after total PTx suggests that subtotal PTx is the initial operation of choice in this setting.

  7. Genetic diagnosis of a Chinese multiple endocrine neoplasia type 2A family through whole genome sequencing

    Indian Academy of Sciences (India)

    ZHEN-FANG DU; PENG-FEI LI; JIAN-QIANG ZHAO; ZHI-LIE CAO; FENG LI; JU-MING MA; XIAO-PING QI

    2017-06-01

    Approximately 98% of patients with multiple endocrine neoplasia type 2A (MEN 2A) have an identifiable RETmutation. Prophylactic or early total thyroidectomy or pheochromocytoma/parathyroid removal in patients can bepreventative or curative and has become standard management. The general strategy for RET screening on familymembers at risk is to sequence the most commonly affected exons and, if negative, to extend sequencing to additionalexons. However, different families with MEN 2A due to the same RET mutation often have significant variability inthe clinical exhibition of disease and aggressiveness of the MTC, which implies additional genetic loci exsit beyondRET coding region. Whole genome sequencing (WGS) greatly expands the breadth of screening from genes associatedwith a particular disease to the whole genome and, potentially, all the information that the genome containsabout diseases or traits. This is presumably due to additive effect of disease modifying factors. In this study, weperformed WGS on a typical Chinese MEN 2A proband and identified the pathogenic RET p.C634R mutation. Wealso identified several neutral variants within RET and pheochromocytoma-related genes. Moreover, we found severalinteresting structural variants including genetic deletions (RSPO1, OVCH2 and AP3S1, etc.) and fusion transcripts(FSIP1-BAZ2A, etc.).

  8. Switching from multiple daily injections to CSII pump therapy: insulin expenditures in type 2 diabetes.

    Science.gov (United States)

    David, Guy; Gill, Max; Gunnarsson, Candace; Shafiroff, Jeff; Edelman, Steven

    2014-11-01

    To identify variations in expenditures and utilization of insulin and other antidiabetes medications by comparing patients with type 2 diabetes mellitus using continuous subcutaneous insulin infusion (CSII) pump therapy versus multiple daily injection (MDI) therapy. Truven Health Analytics MarketScan Commercial Claims and Encounters Database and Medicare Supplemental Database for 2006 to 2010 were used in a difference-in-differences approach that took advantage of variation in the timing of the switch from MDI therapy to CSII pump therapy. Continuous users of MDI therapy throughout the study period were compared with those who switched to the CSII pump therapy during this period. Specifications included: coefficient estimates from cross-sectional ordinary least squares (OLS) regressions with: 1) no additional controls, 2) controls for patient demographics and comorbidities, and 3) patient fixed effects. Propensity score matching at baseline mitigated concerns regarding patient selection bias. While insulin expenditures rose during the study period, switching to CSII pump therapy led to sizable reductions in insulin expenditures. This reduction in insulin expenditures due to switching varied between $657 (standard error [SE] $126; Pinsulin expenditures among MDI patients who switched to CSII pump therapy at various times throughout the study period.

  9. 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.

  10. miR-29b contributes to multiple types of muscle atrophy

    Science.gov (United States)

    Li, Jin; Chan, Mun Chun; Yu, Yan; Bei, Yihua; Chen, Ping; Zhou, Qiulian; Cheng, Liming; Chen, Lei; Ziegler, Olivia; Rowe, Glenn C.; Das, Saumya; Xiao, Junjie

    2017-01-01

    A number of microRNAs (miRNAs, miRs) have been shown to play a role in skeletal muscle atrophy, but their role is not completely understood. Here we show that miR-29b promotes skeletal muscle atrophy in response to different atrophic stimuli in cells and in mouse models. miR-29b promotes atrophy of myotubes differentiated from C2C12 or primary myoblasts, and conversely, its inhibition attenuates atrophy induced by dexamethasone (Dex), TNF-α and H2O2 treatment. Targeting of IGF-1 and PI3K(p85α) by miR-29b is required for induction of muscle atrophy. In vivo, miR-29b overexpression is sufficient to promote muscle atrophy while inhibition of miR-29b attenuates atrophy induced by denervation and immobilization. These data suggest that miR-29b contributes to multiple types of muscle atrophy via targeting of IGF-1 and PI3K(p85α), and that suppression of miR-29b may represent a therapeutic approach for muscle atrophy induced by different stimuli. PMID:28541289

  11. 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.

  12. 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...

  13. 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.

  14. 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.

  15. 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.

  16. 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

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. 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.

  2. [Continuous insulin therapy versus multiple insulin injections in the management of type 1 diabetes: a longitutinal study].

    Science.gov (United States)

    Ribeiro, Maria Estela Bellini; Del Roio Liberatore Junior, Raphael; Custodio, Rodrigo; Martinelli Junior, Carlos Eduardo

    2016-01-01

    To compare multiple doses of insulin and continuous insulin infusion therapy as treatment for type 1 diabetes melito. 40 patients with type 1 diabetes melito (21 female) with ages between 10 and 20 years (mean=14.2) and mean duration of diabetes of 7 years used multiple doses of insulin for at least 6 months and after that, continuous insulin infusion therapy for at least 6 months. Each one of the patients has used multiple doses of insulin and continuous insulin infusion therapy. For analysis of HbA1c, mean glycated hemoglobin levels (mHbA1c) were obtained during each treatment period (multiple doses of insulin and continuous insulin infusion therapy period). Although mHbA1c levels were lower during continuous insulin infusion therapy the difference was not statistically significant. During multiple doses of insulin, 14.2% had mHbA1c values below 7.5% vs. 35.71% while on continuous insulin infusion therapy; demonstrating better glycemic control with the use of continuous insulin infusion therapy. During multiple doses of insulin, 15-40 patients have severe hypoglycemic events versus 5-40 continuous insulin infusion therapy. No episodes of ketoacidosis events were recorded. This is the first study with this design comparing multiple doses of insulin and continuous insulin infusion therapy in Brazil showing no significant difference in HbA1c; hypoglycemic events were less frequent during continuous insulin infusion therapy than during multiple doses of insulin and the percentage of patients who achieved a HbA1c less than 7.5% was greater during continuous insulin infusion therapy than multiple doses of insulin therapy. Copyright © 2015 Sociedade de Pediatria de São Paulo. Publicado por Elsevier Editora Ltda. All rights reserved.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. Urinary heparanase activity in patients with Type 1 and Type 2 diabetes.

    Science.gov (United States)

    Rops, Angelique L W M M; van den Hoven, Mabel J; Veldman, Bart A; Salemink, Simone; Vervoort, Gerald; Elving, Lammy D; Aten, Jan; Wetzels, Jack F; van der Vlag, Johan; Berden, Jo H M

    2012-07-01

    A reduced heparan sulphate (HS) expression in the glomerular basement membrane of patients with overt diabetic nephropathy is associated with an increased glomerular heparanase expression. We investigated the possible association of urinary heparanase activity with the development of proteinuria in patients with Type 1 diabetes (T1D), Type 2 diabetes (T2D), or membranous glomerulopathy (MGP) as non-diabetic disease controls. Heparanase activity, albumin, HS and creatinine were measured in the urine of patients with T1D (n=58) or T2D (n=31), in patients with MGP (n=52) and in healthy controls (n=10). Heparanase messenger RNA (mRNA) expression in leukocytes was determined in a subgroup of patients with T1D (n=19). Urinary heparanase activity was increased in patients with T1D and T2D, which was more prominent in patients with macroalbuminuria, whereas no activity could be detected in healthy controls. Albuminuria levels were associated with increased urinary heparanase activity in diabetic patients (r=0.20; P<0.05) but not in patients with MGP (r=0.11; P=0.43). A lower urinary heparanase activity was observed in diabetic patients treated with inhibitors of the renin-angiotensin-aldosterone system (RAAS), when compared to diabetic patients treated with other anti-hypertensives. Additionally, urinary heparanase activity was associated with age in T1D and MGP. In MGP, heparanase activity and β2-microglobulin excretion correlated. In patients with T1D, no differences in heparanase mRNA expression in leukocytes could be observed. Urinary heparanase activity is increased in diabetic patients with proteinuria. However, whether increased heparanase activity is a cause or consequence of proteinuria requires additional research.

  8. Randomized-controlled trials of levetiracetam as an adjunctive therapy in epilepsy of multiple seizure types.

    Science.gov (United States)

    Fang, Youxin; Wu, Xunyi; Xu, Lan; Tang, Xinghua; Wang, Jianhong; Zhu, Guoxing; Hong, Zhen

    2014-01-01

    This meta-analysis aimed to systematically collect and synthesize the current evidence regarding the efficacy and tolerability of levetiracetam (LEV) as an adjunctive therapy for adults and children suffering from idiopathic and secondary epilepsy of multiple seizure types. We selected randomized-controlled trials (RCT) of LEV as an adjunctive therapy in epilepsy according to predefined criteria. Outcome measures included a > or =50% reduction in seizure frequency, seizure freedom, and adverse events. Thirteen RCT were analyzed. Results showed that the efficacy of adjunctive LEV was superior to placebo both in achieving > or =50% reduction in seizure frequency (pooled odds ratio [OR] 3.36, 95% confidence interval [CI] 2.78-4.07, Z=12.46; pseizure freedom (pooled OR 4.72, 95% CI 2.96-7.54, Z=6.50; p or =50% reduction in seizure frequency, and chi-squared=0.49, I2=0% in seizure freedom). Subgroup analysis suggested similar effects across different dosages in adults. The incidence of adverse reactions was not significantly different between the LEV group and the placebo group. The adverse events of relatively high incidence in the LEV group included somnolence, agitation, dizziness, asthenia, and infection. Incidence of serious adverse reaction such as rash and white blood cells and platelets decreasing was quite low. Adjunctive therapy with LEV was superior to placebo in reducing the frequency of seizures in patients with partial and idiopathic generalized epilepsy with effect in both adults and children, and demonstrated good tolerance in patients with epilepsy. Copyright © 2013 Elsevier Ltd. All rights reserved.

  9. Pathways targeted by antidiabetes drugs are enriched for multiple genes associated with type 2 diabetes risk.

    Science.gov (United States)

    Segrè, Ayellet V; Wei, Nancy; Altshuler, David; Florez, Jose C

    2015-04-01

    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 therefore tested whether other genes/pathways targeted by antidiabetes drugs are associated with T2D. We compiled a list of 102 genes in pathways targeted by marketed antidiabetic medications and applied Gene Set Enrichment Analysis (MAGENTA [Meta-Analysis Gene-set Enrichment of variaNT Associations]) to this gene set, using available GWAS meta-analyses for T2D and seven quantitative glycemic traits. We detected a strong enrichment of drug target genes associated with T2D (P = 2 × 10(-5); 14 potential new associations), primarily driven by insulin and thiazolidinedione (TZD) targets, which was replicated in an independent meta-analysis (Metabochip). The glycemic traits yielded no enrichment. The T2D enrichment signal was largely due to multiple genes of modest effects (P = 4 × 10(-4), after removing known loci), highlighting new associations for follow-up (ACSL1, NFKB1, SLC2A2, incretin targets). Furthermore, we found that TZD targets were enriched for LDL cholesterol associations, illustrating the utility of this approach in identifying potential side effects. These results highlight the potential biomedical relevance of genes revealed by GWAS and may provide new avenues for tailored therapy and T2D treatment design. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  10. 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.

  11. 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.

  12. Brucella Modulates Secretory Trafficking via Multiple Type IV Secretion Effector Proteins

    Science.gov (United States)

    Myeni, Sebenzile; Child, Robert; Ng, Tony W.; Kupko, John J.; Wehrly, Tara D.; Porcella, Stephen F.; Knodler, Leigh A.; Celli, Jean

    2013-01-01

    The intracellular pathogenic bacterium Brucella generates a replicative vacuole (rBCV) derived from the endoplasmic reticulum via subversion of the host cell secretory pathway. rBCV biogenesis requires the expression of the Type IV secretion system (T4SS) VirB, which is thought to translocate effector proteins that modulate membrane trafficking along the endocytic and secretory pathways. To date, only a few T4SS substrates have been identified, whose molecular functions remain unknown. Here, we used an in silico screen to identify putative T4SS effector candidate proteins using criteria such as limited homology in other bacterial genera, the presence of features similar to known VirB T4SS effectors, GC content and presence of eukaryotic-like motifs. Using β-lactamase and CyaA adenylate cyclase reporter assays, we identified eleven proteins translocated into host cells by Brucella, five in a VirB T4SS-dependent manner, namely BAB1_0678 (BspA), BAB1_0712 (BspB), BAB1_0847 (BspC), BAB1_1671 (BspE) and BAB1_1948 (BspF). A subset of the translocated proteins targeted secretory pathway compartments when ectopically expressed in HeLa cells, and the VirB effectors BspA, BspB and BspF inhibited protein secretion. Brucella infection also impaired host protein secretion in a process requiring BspA, BspB and BspF. Single or combined deletions of bspA, bspB and bspF affected Brucella ability to replicate in macrophages and persist in the liver of infected mice. Taken together, these findings demonstrate that Brucella modulates secretory trafficking via multiple T4SS effector proteins that likely act coordinately to promote Brucella pathogenesis. PMID:23950720

  13. Radiological surveillance in multiple endocrine neoplasia type 1: a double-edged sword?

    Directory of Open Access Journals (Sweden)

    Ruth Therese Casey

    2017-03-01

    Full Text Available Context: Multiple endocrine neoplasia type 1 (MEN1 is a hereditary condition characterised by the predisposition to hyperplasia/tumours of endocrine glands. MEN1-related disease, moreover, malignancy related to MEN1, is increasingly responsible for death in up to two-thirds of patients. Although patients undergo radiological and biochemical surveillance, current recommendations for radiological monitoring are based on non-prospective data with little consensus or evidence demonstrating improved outcome from this approach. Here, we sought to determine whether cumulative radiation exposure as part of the recommended radiological screening programme posed a distinct risk in a cohort of patients with MEN1.Patients and study design: A retrospective review of 43 patients with MEN1 attending our institution between 2007 and 2015 was performed. Demographic and clinical information including phenotype was obtained for all patients. We also obtained details regarding all radiological procedures performed as part of MEN1 surveillance or disease localisation. An estimated effective radiation dose (ED for each individual patient was calculated.Results: The mean ED for the total patient cohort was 121 mSv, and the estimated mean lifetime risk of cancer secondary to radiation exposure was 0.49%. Patients with malignant neuroendocrine tumours (NETS had significantly higher ED levels compared to patients without metastatic disease (P < 0.0022.Conclusions: In MEN1, radiological surveillance is associated with clinically significant exposure to ionising radiation. In patients with MEN1, multi-modality imaging strategies designed to minimise this exposure should be considered.

  14. 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

  15. 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

  16. Thoracic and duodenopancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1: natural history and function of menin in tumorigenesis.

    Science.gov (United States)

    Pieterman, C R C; Conemans, E B; Dreijerink, K M A; de Laat, J M; Timmers, H Th M; Vriens, M R; Valk, G D

    2014-06-01

    Mutations of the multiple endocrine neoplasia type 1 (MEN1) gene lead to loss of function of its protein product menin. In keeping with its tumor suppressor function in endocrine tissues, the majority of the MEN1-related neuroendocrine tumors (NETs) show loss of heterozygosity (LOH) on chromosome 11q13. In sporadic NETs, MEN1 mutations and LOH are also reported, indicating common pathways in tumor development. Prevalence of thymic NETs (thNETs) and pulmonary carcinoids in MEN1 patients is 2-8%. Pulmonary carcinoids may be underreported and research on natural history is limited, but disease-related mortality is low. thNETs have a high mortality rate. Duodenopancreatic NETs (dpNETs) are multiple, almost universally found at pathology, and associated with precursor lesions. Gastrinomas are usually located in the duodenal submucosa while other dpNETs are predominantly pancreatic. dpNETs are an important determinant of MEN1-related survival, with an estimated 10-year survival of 75%. Survival differs between subtypes and apart from tumor size there are no known prognostic factors. Natural history of nonfunctioning pancreatic NETs needs to be redefined because of increased detection of small tumors. MEN1-related gastrinomas seem to behave similar to their sporadic counterparts, while insulinomas seem to be more aggressive. Investigations into the molecular functions of menin have led to new insights into MEN1-related tumorigenesis. Menin is involved in gene transcription, both as an activator and repressor. It is part of chromatin-modifying protein complexes, indicating involvement of epigenetic pathways in MEN1-related NET development. Future basic and translational research aimed at NETs in large unbiased cohorts will clarify the role of menin in NET tumorigenesis and might lead to new therapeutic options.

  17. 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.

  18. 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 pa...... 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%....

  19. 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).…

  20. 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…

  1. 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…

  2. 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…

  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. 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.

  5. Home uterine activity monitoring: an evidence review of its utility in multiple gestations.

    Science.gov (United States)

    Reichmann, James P

    2009-09-01

    To examine the medical evidence regarding the application of home uterine activity monitoring for multiple gestations. All of the published peer-reviewed articles on the topic were assembled and assigned a level of evidence based on research design. The search uncovered 9 articles, including 3 Level I randomized, controlled trials; 1 level II matched cohort trial; and 5 level III case series. The first 5 trials all showed promising results for home uterine activity monitoring applied to multiple gestations. Ultimately, however, 14 years after the introduction of home uterine activity monitoring, the largest randomized, controlled trial was published, and it demonstrated that pregnancy outcomes were identical for patients with home uterine activity monitoring and patients receiving weekly calls from a nurse. A subsequent National Institute of Child Health and Human Development published trial may provide a clue as to why the large, randomized, controlled trial demonstrated no difference. Contractions in multiple gestations are not predictive of preterm birth.

  6. 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…

  7. Plasminogen activator inhibitor (type-1) in rat adrenal medulla.

    Science.gov (United States)

    Eriksen, J; Kristensen, P; Pyke, C; Danø, K

    1989-01-01

    Plasminogen activator inhibitor type-1 (PAI-1) was identified in extracts of rat adrenal medulla, and its immunohistochemical localization was studied together with that of tissue-type plasminogen activator (t-PA). By staining of adjacent sections and by double-staining of the same section we demonstrate that the same cells of the adrenal medulla contain both PAI-1 and t-PA immunoreactivity in the cytoplasm. In addition a few ganglion cells of the adrenal medulla were found to contain PAI-1 but not t-PA. Neither of the components were found in the adrenal cortex. Analysis of extracts from isolated adrenal medulla using reverse zymography showed the presence of a plasminogen activator inhibitor with Mr approximately 46,000. The inhibitory activity disappeared when the extract was passed through a column with sepharose-coupled anti-PAI-1 IgG, while the run-through from a similar column coupled with preimmune IgG still contained the inhibitor. The present findings suggest that PAI-1 could play a role in the regulation of t-PA activity in the rat adrenal gland medullary cells.

  8. 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.

  9. Teacher Subject Specialisms and Their Relationships to Learning Styles, Psychological Types and Multiple Intelligences: Implications for Course Development

    Science.gov (United States)

    Perry, Chris; Ball, Ian

    2004-01-01

    This study explores issues in teacher education that increase our understanding of, and response to, the individual differences displayed by learners. A large undergraduate teacher education cohort provided evidence of the range and distribution of preferences in learning styles, psychological types and multiple intelligences. This information…

  10. 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

  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. 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

  14. 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

  15. Physical Activity: The Forgotten Tool for Type 2 Diabetes Management

    Directory of Open Access Journals (Sweden)

    Sheri R. Colberg

    2012-05-01

    Full Text Available Individuals who are currently sedentary, unfit, or overweight can benefit metabolically from simply taking breaks from sitting. Since avoidance of sedentary behavior appears to have a large impact on glycemic management, all individuals with type 2 diabetes should be encouraged to minimally engage in greater daily movement to better manage their diabetes and body weight. In addition, engaging in physical activity of any intensity (including low-intensity ones likely positively impacts insulin action and blood glucose control acutely. Moreover, as long as total caloric expenditure during exercise is matched (i.e., total exercise dose, daily exercise may be done every other day instead with the same glycemic results, although at least 150 minutes of weekly physical activity is recommended. Both aerobic and resistance training are important for individuals with diabetes, and ideally a program that combines the two types of training should be undertaken to achieve maximal glycemic and other benefits. Once individuals have successfully implemented more daily movement into their lifestyle, they will be more likely to participate in structured forms of physical activity to gain additional benefits. All clinicians working with individuals with either type 2 diabetes or prediabetes should consider incorporating these suggestions into care plans to improve their patients’ glycemic management.

  16. 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

  17. 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...

  18. 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

  19. 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.

  20. Retroviral Replicating Vectors Deliver Cytosine Deaminase Leading to Targeted 5-Fluorouracil-Mediated Cytotoxicity in Multiple Human Cancer Types.

    Science.gov (United States)

    Twitty, Chris G; Diago, Oscar R; Hogan, Daniel J; Burrascano, Cindy; Ibanez, Carlos E; Jolly, Douglas J; Ostertag, Derek

    2016-02-01

    Toca 511 is a modified retroviral replicating vector based on Moloney γ-retrovirus with an amphotropic envelope. As an investigational cancer treatment, Toca 511 preferentially infects cancer cells without direct cell lysis and encodes an enhanced yeast cytosine deaminase that converts the antifungal drug 5-fluorocytosine to the anticancer drug, 5-fluorouracil. A panel of established human cancer cell lines, derived from glioblastoma, colon, and breast cancer tissue, was used to evaluate parameters critical for effective anticancer activity. Gene transfer, cytosine deaminase production, conversion of 5-fluorocytosine to 5-fluorouracil, and subsequent cell killing occurred in all lines tested. We observed >50% infection within 25 days in all lines and 5-fluorocytosine LD50 values between 0.02 and 6 μg/ml. Although we did not identify a small number of key criteria, these studies do provide a straightforward approach to rapidly gauge the probability of a Toca 511 and 5-fluorocytosine treatment effect in various cancer indications: a single MTS assay of maximally infected cancer cell lines to determine 5-fluorocytosine LD50. The data suggest that, although there can be variation in susceptibility to Toca 511 and 5-fluorocytosine because of multiple mechanistic factors, this therapy may be applicable to a broad range of cancer types and individuals.

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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

  6. 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.

  7. 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.

  8. 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...

  9. 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

  10. 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.

  11. Epidermis-type lipoxygenase 3 regulates adipocyte differentiation and peroxisome proliferator-activated receptor gamma activity

    DEFF Research Database (Denmark)

    Hallenborg, Philip; Jørgensen, Claus; Petersen, Rasmus K

    2010-01-01

    differentiation has remained enigmatic. Previously, we showed that lipoxygenase (LOX) activity is involved in activation of PPAR gamma during the early stages of adipocyte differentiation. Of the seven known murine LOXs, only the unconventional LOX epidermis-type lipoxygenase 3 (eLOX3) is expressed in 3T3-L1...

  12. Comparative DNA methylation analysis to decipher common and cell type-specific patterns among multiple cell types.

    Science.gov (United States)

    Yang, Xiaofei; Shao, Xiaojian; Gao, Lin; Zhang, Shihua

    2016-11-01

    DNA methylation has been proved to play important roles in cell development and complex diseases through comparative studies of DNA methylation profiles across different tissues and samples. Current studies indicate that the regulation of DNA methylation to gene expression depends on the genomic locations of CpGs. Common DNA methylation patterns shared across different cell types and tissues are abundant, and they are likely involved in the basic functions of cell development, such as housekeeping functions. By way of contrast, cell type-specific DNA methylation patterns show distinct functional relevance with cell type specificity. Additionally, abnormal DNA methylation patterns are extensively involved in tumour development. Pan-cancer methylation patterns reveal common mechanisms and new similarities of different cancers, while cancer-specific patterns are relating to tumour heterogeneity and patient survival. Moreover, DNA methylation patterns in specific cancer are relevant with diverse regulatory elements such as enhancers and long non-coding RNAs. In this review, we survey the recent advances on DNA methylation patterns in normal or tumour states to illustrate their potential roles in cell development and cell canceration. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  13. 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.

  14. 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.

  15. 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......We propose a non-intrusive eye tracking system intended for the use of everyday gaze typing using web cameras. We argue that high precision in gaze tracking is not needed for on-screen typing due to natural language redundancy. This facilitates the use of low-cost video components for advanced...... to infer the state of the eye such as eye corners and the pupil location under scale and rotational changes....

  16. 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...

  17. Antibacterial Activity of Germacrane Type Sesquiterpenes from Curcuma heyneana Rhizomes

    Directory of Open Access Journals (Sweden)

    Hartiwi Diastuti

    2014-03-01

    Full Text Available The isolation of terpenoids from C. heyneana rhizomes and their antibacterial activity have been conducted. The terpenoids were isolated by using vacuum liquid chromatography and radial chromatography. The structures of the compounds were determined based on spectroscopic data (1H-NMR, 13C-NMR (1D and 2D. The antibacterial activity was carried out by using microdilution method and evaluated against eight bacteria. Three germacrane type sesquiterpenes have been isolated from C. heyneana rhizhomes and were identified as germacrone, dehydrocurdione, and 1(10,4(5-diepoxygermacrone. Germacrone showed highest antibacterial activity against P. aeruginosa with MIC values of 15.6 µg/mL and MBC values 31.2 µg/mL. Dehydrocurdione showed highest antibacterial activity against B. subtilis with MIC values of 31.2 µg/mL and MBC values of 31.2 µg/mL. However, 1(10,4(5-diepoxygermacrone showed a weak antibacterial activity.

  18. Multiple stress response of lowland stream benthic macroinvertebrates depends on habitat type.

    Science.gov (United States)

    Graeber, Daniel; Jensen, Tinna M; Rasmussen, Jes J; Riis, Tenna; Wiberg-Larsen, Peter; Baattrup-Pedersen, Annette

    2017-12-01

    Worldwide, lowland stream ecosystems are exposed to multiple anthropogenic stress due to the combination of water scarcity, eutrophication, and fine sedimentation. The understanding of the effects of such multiple stress on stream benthic macroinvertebrates has been growing in recent years. However, the interdependence of multiple stress and stream habitat characteristics has received little attention, although single stressor studies indicate that habitat characteristics may be decisive in shaping the macroinvertebrate response. We conducted an experiment in large outdoor flumes to assess the effects of low flow, fine sedimentation, and nutrient enrichment on the structure of the benthic macroinvertebrate community in riffle and run habitats of lowland streams. For most taxa, we found a negative effect of low flow on macroinvertebrate abundance in the riffle habitat, an effect which was mitigated by fine sedimentation for overall community composition and the dominant shredder species (Gammarus pulex) and by nutrient enrichment for the dominant grazer species (Baetis rhodani). In contrast, fine sediment in combination with low flow rapidly affected macroinvertebrate composition in the run habitat, with decreasing abundances of many species. We conclude that the effects of typical multiple stressor scenarios on lowland stream benthic macroinvertebrates are highly dependent on habitat conditions and that high habitat diversity needs to be given priority by stream managers to maximize the resilience of stream macroinvertebrate communities to multiple stress. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. 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

    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...

  20. 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

  1. 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.

  2. 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.

  3. Switching from multiple daily injections to CSII pump therapy: insulin expenditures in type 2 diabetes

    National Research Council Canada - National Science Library

    David, Guy; Gill, Max; Gunnarsson, Candace; Shafiroff, Jeff; Edelman, Steven

    2014-01-01

    To identify variations in expenditures and utilization of insulin and other antidiabetes medications by comparing patients with type 2 diabetes mellitus using continuous subcutaneous insulin infusion (CSII...

  4. 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…

  5. 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

  6. 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…

  7. 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

  8. 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.

  9. 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...

  10. 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…

  11. 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...

  12. Multiple Reflex Pathways Contribute to Bladder Activation by Intraurethral Stimulation in Persons With Spinal Cord Injury.

    Science.gov (United States)

    McGee, Meredith J; Swan, Brandon D; Danziger, Zachary C; Amundsen, Cindy L; Grill, Warren M

    2017-08-08

    To measure the urodynamic effects of electrical co-stimulation of 2 individual sites in the proximal and distal urethra in persons with spinal cord injury (SCI). This work was motivated by preclinical findings that selective co-stimulation of the cranial urethral sensory nerve and the dorsal genital nerve, which innervate the proximal and distal portions of the urethra, respectively, increased reflex bladder activation and voiding efficiency. Electrical co-stimulation of urethral afferents was conducted in persons with chronic SCI during urodynamics. The effects of different frequencies of intraurethral stimulation at multiple urethral locations on bladder pressure and pelvic floor electromyographic activity were measured. Electromyographic activity indicated that multiple reflex pathways were recruited through stimulation that contributed to bladder activation. The size of reflex bladder contractions evoked by stimulation was dependent on stimulation location or reflex activated and stimulation frequency. Pudendal nerve afferents are a promising target to restore lost bladder control, as stimulation with different frequencies may be used to treat urinary incontinence and increase continent volumes or to generate stimulation-evoked bladder contractions for on-demand voiding. This work identified that co-stimulation of multiple afferent reflex pathways can enhance activation of spinal circuits and may enable improved bladder emptying in SCI when stimulation of a single pathway is not sufficient. Copyright © 2017 Elsevier Inc. All rights reserved.

  13. 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.

  14. Optically detected magnetic resonance study of a type-II GaAs/AlAs multiple quantum well

    Science.gov (United States)

    van Kesteren, H. W.; Cosman, E. C.; Greidanus, F. J. A. M.; Dawson, P.; Moore, K. J.; Foxon, C. T.

    1988-07-01

    In a type-II GaAs/AlAs multiple quantum well three optically detected magnetic resonance lines and two level anticrossings were observed. Two of the resonance lines and the two level anticrossings are in agreement with the electronic level scheme of the heavy-hole exciton. The third resonance line is in accordance with a magnetic spin resonance of an unbound electron. These optically detected magnetic resonance measurements open up the possibility to obtain detailed information about the excitons in and the band structure of type-II quantum wells.

  15. 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.

  16. 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}...

  17. 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.

  18. 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...

  19. Promising multiple-epitope recombinant vaccine against foot-and-mouth disease virus type O in swine.

    Science.gov (United States)

    Shao, Jun-Jun; Wong, Chung Kai; Lin, Tong; Lee, Shuk Kwan; Cong, Guo-Zheng; Sin, Fion Wai Yee; Du, Jun-Zheng; Gao, Shan-Dian; Liu, Xiang-Tao; Cai, Xue-Peng; Xie, Yong; Chang, Hui-Yun; Liu, Ji-Xing

    2011-01-01

    In order to develop a completely safe immunogen to replace the traditional inactivated vaccine, a tandem-repeat multiple-epitope recombinant vaccine against foot-and-mouth disease (FMD) virus (FMDV) type O was developed. It contained three copies each of residues 141 to 160 and 200 to 213 of VP1 of the O/China/99 strain of FMDV coupled with a swine immunoglobulin G heavy-chain constant region (scIgG). The data showed that the multiple-epitope recombinant vaccine elicited high titers of anti-FMDV specific antibodies in swine at 30 days postvaccination (dpv) and conferred complete protection against a challenge with 10³ 50% swine infective doses of the O/China/99 strain. The anti-FMDV specific antibody titers were not significantly different between the multiple-epitope recombinant vaccine and the traditional vaccine (t test, P > 0.05). The number of 50% pig protective doses was 6.47, which is higher than the number recommended by the World Organization for Animal Health. The multiple-epitope recombinant vaccine resulted in a duration of immunity of at least 6 months. We speculate that the multiple-epitope recombinant vaccine is a promising vaccine that may replace the traditional inactivated vaccine for the prevention and control of FMD in swine in the future.

  20. 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.

  1. 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

  2. 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

  3. 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

  4. 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.

  5. 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.)

  6. 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.

  7. 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.

  8. Postoperative Complications After Prophylactic Thyroidectomy for Very Young Patients With Multiple Endocrine Neoplasia Type 2

    OpenAIRE

    Kluijfhout, Wouter P; van Beek, Dirk-Jan; Verrijn Stuart, Annemarie A.; Lodewijk, Lutske; Gerlof D. Valk; Van der Zee, David C.; Vriens, Menno R.; Inne H. M. Borel Rinkes

    2015-01-01

    Abstract The aim of this study was to investigate whether younger age at surgery is associated with the increased incidence of postoperative complications after prophylactic thyroidectomy in pediatric patients with multiple endocrine neoplasia (MEN) 2. The shift toward earlier thyroidectomy has resulted in significantly less medullary thyroid carcinoma (MTC)-related morbidity and mortality. However, very young pediatric patients might have a higher morbidity rate compared with older patients....

  9. 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.

  10. 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

  11. 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.

  12. 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.

  13. 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...

  14. Legitimating New Forms of Organizing and New International Activities in the Eyes of Multiple Stakeholders

    DEFF Research Database (Denmark)

    Turcan, Romeo V.

    by its multiple stakeholders; and (2) what legitimation strategies it developed and adopted to legitimate itself in the eyes of its multiple stakeholders. Theoretically, the paper is grounded within legitimation theory. The empirical context is defined by a new, international NGO entering an established...... NGO sector located in an emerging economy. In this context, in addition to challenges pertained to unfamiliar institutional settings in an emerging economy - liability of foreignness, this NGO had to overcome another set of challenges related to its new activities - liability of newness...

  15. 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.

  16. Multiple Types of Childhood and Adult Violence Among Homeless and Unstably Housed Women in San Francisco.

    Science.gov (United States)

    Wong, Lauren H; Shumway, Martha; Flentje, Annesa; Riley, Elise D

    2016-12-01

    This study examined the relationship between different forms of childhood violence (emotional, physical, and sexual) and these same forms of violence in adulthood, using a crosssectional baseline survey of 298 homeless and unstably housed women in San Francisco, California. We also examined other related factors, including mental illnesses diagnosis, sex exchange, jail time, HIV status, and sociodemographic information. Regression analysis indicated that although several of these factors were associated with experiences of violence as an adult, specific types of child violence (e.g., sexual violence) predicted instances of that same type of violence as an adult but not necessarily other types. Thus, risk of adult violence among low-income women may be better predicted and addressed through histories of same-type childhood violence, despite years of intervening exposures and stressors.

  17. 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. .

  18. 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.

  19. 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...

  20. 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

  1. 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...

  2. 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.

  3. High intensity training may reverse the fiber type specific decline in myogenic stem cells in multiple sclerosis patients

    Directory of Open Access Journals (Sweden)

    Jean eFarup

    2016-05-01

    Full Text Available Multiple sclerosis (MS is associated with loss of skeletal muscle mass and function. The myogenic stem cells (satellite cells – SCs are instrumental to accretion of myonuclei, but remain to be investigated in MS. The present study aimed to compare the SC and myonuclei content between MS patients (n=23 and age matched healthy controls (HC, n=18. Furthermore, the effects of 12 weeks of high intensity training on SC and myonuclei content were explored in MS. Muscle biopsies were obtained from m. Vastus Lateralis at baseline (MS+HC and following 12 weeks of training (MS only. Frozen biopsies were sectioned followed by immunohistochemical analysis for fiber type specific SCs (Pax7+, myonuclei (MN and central nuclei content and fiber cross-sectional area (fCSA using ATPase histochemistry. At baseline the SCs per fiber was lower in type II compared to type I fiber in both MS (119%, p<0.01 and HC (69%, p<0.05, whereas the SCs per fCSA was lower in type II fibers compared to type I only in MS (72%, p<0.05. No differences were observed in MN or central nuclei between MS and HC. Following training the type II fiber SCs per fiber and fCSA in MS patients increased by 165% (p<0.05 and 135% (p<0.05, respectively. Furthermore, the type II fiber MN content increased by 35% (p<0.05 following training. In conclusion, the SC content is lower in type II compared to type I fibers in both MS and HC. Furthermore, high intensity training was observed to selectively increase the SC and myonuclei content in type II fibers in MS patients.

  4. 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...

  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. 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.

  7. Fha interaction with phosphothreonine of TssL activates type VI secretion in Agrobacterium tumefaciens.

    Science.gov (United States)

    Lin, Jer-Sheng; Wu, Hsin-Hui; Hsu, Pang-Hung; Ma, Lay-Sun; Pang, Yin-Yuin; Tsai, Ming-Daw; Lai, Erh-Min

    2014-03-01

    The type VI secretion system (T6SS) is a widespread protein secretion system found in many Gram-negative bacteria. T6SSs are highly regulated by various regulatory systems at multiple levels, including post-translational regulation via threonine (Thr) phosphorylation. The Ser/Thr protein kinase PpkA is responsible for this Thr phosphorylation regulation, and the forkhead-associated (FHA) domain-containing Fha-family protein is the sole T6SS phosphorylation substrate identified to date. Here we discovered that TssL, the T6SS inner-membrane core component, is phosphorylated and the phosphorylated TssL (p-TssL) activates type VI subassembly and secretion in a plant pathogenic bacterium, Agrobacterium tumefaciens. Combining genetic and biochemical approaches, we demonstrate that TssL is phosphorylated at Thr 14 in a PpkA-dependent manner. Further analysis revealed that the PpkA kinase activity is responsible for the Thr 14 phosphorylation, which is critical for the secretion of the T6SS hallmark protein Hcp and the putative toxin effector Atu4347. TssL phosphorylation is not required for the formation of the TssM-TssL inner-membrane complex but is critical for TssM conformational change and binding to Hcp and Atu4347. Importantly, Fha specifically interacts with phosphothreonine of TssL via its pThr-binding motif in vivo and in vitro and this interaction is crucial for TssL interaction with Hcp and Atu4347 and activation of type VI secretion. In contrast, pThr-binding ability of Fha is dispensable for TssM structural transition. In conclusion, we discover a novel Thr phosphorylation event, in which PpkA phosphorylates TssL to activate type VI secretion via its direct binding to Fha in A. tumefaciens. A model depicting an ordered TssL phosphorylation-induced T6SS assembly pathway is proposed.

  8. 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

  9. 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.

  10. 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...

  11. Diagnostic and therapeutic approach to multiple endocrine neoplasia type 2B in pediatric patients.

    Science.gov (United States)

    Torre, M; Martucciello, G; Ceccherini, I; Lerone, M; Aicardi, M; Gambini, C; Jasonni, V

    2002-09-01

    Multiple endocrine neoplasia (MEN) 2B is a hereditary syndrome including medullary thyroid carcinoma (MTC), pheochromocytoma, gastrointestinal (GI) disorders, marfanoid facies, and multiple ganglioneuromas. MTC is the major cause of mortality, and often appears during the 1st decade of life. RET proto-oncogene mutations are responsible for MEN 2B. Other RET mutations cause MEN 2A syndrome, familial MTC, or Hirschsprung's disease. We studied three MEN 2B patients with the aim of delineating the best diagnostic and therapeutic protocol. The gold standards for diagnosis are histochemical study of the rectal mucosa and molecular analysis of RET, which in familial cases detects MEN 2B at a preclinical stage so that early total prophylactic thyroidectomy can be performed. In non-familial cases, the diagnosis can be suggested by the presence of GI symptoms, ganglioneuromas, and/or the typical facies. The intestinal innervation pattern, analyzed with the acetylcholinesterase technique, is pathognomonic for MEN 2B. In our protocol a rectal biopsy is, therefore, the first measure. The surgical treatment of MEN 2B is total thyroidectomy with cervical lymphadenectomy of the central compartment of the neck. When possible, this intervention should be performed prophylactically before 1 year of age.

  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. 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...

  14. 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

  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. Vasotocin maintains multiple call types in the gray treefrog, Hyla versicolor.

    Science.gov (United States)

    Tito, M B; Hoover, M A; Mingo, A M; Boyd, S K

    1999-10-01

    The neuropeptide arginine vasotocin (AVT) influences vocalizations in some anuran amphibians but it is unknown whether AVT alters all vocal behaviors of a species similarly. We first characterized the vocal repertoire of male gray treefrogs (Hyla versicolor). Three different call types were distinguished by unique sets of temporal and spectral features. Second, we examined the effects of AVT on each call type by injecting frogs with either AVT (100 microg; intraperitoneal) or saline and recording subsequent behavior. In the field, AVT maintained advertisement calling, whereas calling ceased in saline-injected animals. Advertisement call rate in AVT-injected males fell significantly and dominant frequency of the call was significantly higher. In the laboratory, AVT induced advertisement calling in males that were not initially vocalizing and dominant frequency was also significantly higher in these males. AVT maintained aggressive calling similarly but the characteristics of aggressive calls were not altered by AVT. There were no significant differences in release call behavior between AVT- and saline-injected groups; however, release call duration decreased significantly in AVT-injected animals, compared with preinjection values for the same animals. The effects of AVT on vocal behavior in this species are therefore not the same for each call type. AVT may act at more general motivational levels in the central nervous system and other neural or endocrine factors may control choice of call type and direct motor output.

  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. 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.

  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. 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.

  3. 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.

  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. 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.

  6. Active Vibration Control and Coupled Vibration Analysis of a Parallel Manipulator with Multiple Flexible Links

    OpenAIRE

    Quan Zhang; Chaodong Li; Jiantao Zhang; Jiamei Jin

    2016-01-01

    This paper addresses the active vibration control and coupled vibration analysis of a planar parallel manipulator (PPM) with three flexible links. Multiple piezoelectric ceramic transducers are integrated with the flexible links to constitute the smart beam structures, and hence the vibration of the flexible link can be self-sensed and self-controlled. To prevent the spillover phenomena and improve the vibration control efficiency, the independent modal space control combined with an input sh...

  7. 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...

  8. 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.

  9. 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.

  10. Statistical Methods for Integrating Multiple Types of High-Throughput Data

    OpenAIRE

    Xie, Yang; Ahn, Chul

    2010-01-01

    Large-scale sequencing, copy number, mRNA, and protein data have given great promise to the biomedical research, while posing great challenges to data management and data analysis. Integrating different types of high-throughput data from diverse sources can increase the statistical power of data analysis and provide deeper biological understanding. This chapter uses two biomedical research examples to illustrate why there is an urgent need to develop reliable and robust methods for integratin...

  11. 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...

  12. Developing a questionnaire on physical activity support of people with (profound) intellectual (and multiple) disabilities : Experiences from the Netherlands

    NARCIS (Netherlands)

    Bossink, Leontien; van der Putten, Annette; Vlaskamp, Carla

    2017-01-01

    Introduction: People with intellectual disabilities (ID) undertake extremely low levels of physical activity, which is even more true in people with profound intellectual and multiple disabilities (PIMD). Physical activity approaches, particularly for people with PIMD, are more likely to be

  13. Two zebrafish G2A homologs activate multiple intracellular signaling pathways in acidic environment

    Energy Technology Data Exchange (ETDEWEB)

    Ichijo, Yuta; Mochimaru, Yuta [Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571 (Japan); Azuma, Morio [Laboratory of Regulatory Biology, Graduate School of Science and Engineering, University of Toyama, 3190-Gofuku, Toyama 930-8555 (Japan); Satou, Kazuhiro; Negishi, Jun [Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571 (Japan); Nakakura, Takashi [Department of Anatomy, Graduate School of Medicine, Teikyo University, 2-11-1 Itabashi-Ku, Tokyo 173-8605 (Japan); Oshima, Natsuki [Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571 (Japan); Mogi, Chihiro; Sato, Koichi [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan); Matsuda, Kouhei [Laboratory of Regulatory Biology, Graduate School of Science and Engineering, University of Toyama, 3190-Gofuku, Toyama 930-8555 (Japan); Okajima, Fumikazu [Laboratory of Signal Transduction, Institute for Molecular and Cellular Regulation, Gunma University, Maebashi 371-8512 (Japan); Tomura, Hideaki, E-mail: tomurah@meiji.ac.jp [Laboratory of Cell Signaling Regulation, Department of Life Sciences, School of Agriculture, Meiji University, Kawasaki 214-8571 (Japan)

    2016-01-01

    Human G2A is activated by various stimuli such as lysophosphatidylcholine (LPC), 9-hydroxyoctadecadienoic acid (9-HODE), and protons. The receptor is coupled to multiple intracellular signaling pathways, including the G{sub s}-protein/cAMP/CRE, G{sub 12/13}-protein/Rho/SRE, and G{sub q}-protein/phospholipase C/NFAT pathways. In the present study, we examined whether zebrafish G2A homologs (zG2A-a and zG2A-b) could respond to these stimuli and activate multiple intracellular signaling pathways. We also examined whether histidine residue and basic amino acid residue in the N-terminus of the homologs also play roles similar to those played by human G2A residues if the homologs sense protons. We found that the zG2A-a showed the high CRE, SRE, and NFAT activities, however, zG2A-b showed only the high SRE activity under a pH of 8.0. Extracellular acidification from pH 7.4 to 6.3 ameliorated these activities in zG2A-a-expressing cells. On the other hand, acidification ameliorated the SRE activity but not the CRE and NFAT activities in zG2A-b-expressing cells. LPC or 9-HODE did not modify any activity of either homolog. The substitution of histidine residue at the 174{sup th} position from the N-terminus of zG2A-a to asparagine residue attenuated proton-induced CRE and NFAT activities but not SRE activity. The substitution of arginine residue at the 32nd position from the N-terminus of zG2A-a to the alanine residue also attenuated its high and the proton-induced CRE and NFAT activities. On the contrary, the substitution did not attenuate SRE activity. The substitution of the arginine residue at the 10th position from the N-terminus of zG2A-b to the alanine residue also did not attenuate its high or the proton-induced SRE activity. These results indicate that zebrafish G2A homologs were activated by protons but not by LPC and 9-HODE, and the activation mechanisms of the homologs were similar to those of human G2A. - Highlights: • Zebrafish two G2A homologs are proton

  14. 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.

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

    Science.gov (United States)

    Lou, Qingqing; Chen, Yufeng; Guo, Xiaohui; Yuan, Li; Chen, Tao; Wang, Chun; Shen, Li; Sun, Zilin; Zhao, Fang; Dai, Xia; Huang, Jin; Yang, Huiying

    2014-01-01

    The aim of the paper is to report the development and psychometric testing of Diabetes Attitude Scale. 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. 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. 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.

  16. 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.

  17. Balancing Type One and Two Errors in Multiple Testing for Differential Expression of Genes.

    Science.gov (United States)

    Gordon, Alexander; Chen, Linlin; Glazko, Galina; Yakovlev, Andrei

    2009-03-15

    A new procedure is proposed to balance type I and II errors in significance testing for differential expression of individual genes. Suppose that a collection, F(k), of k lists of selected genes is available, each of them approximating by their content the true set of differentially expressed genes. For example, such sets can be generated by a subsampling counterpart of the delete-d-jackknife method controlling the per-comparison error rate for each subsample. A final list of candidate genes, denoted by S(*), is composed in such a way that its contents be closest in some sense to all the sets thus generated. To measure "closeness" of gene lists, we introduce an asymmetric distance between sets with its asymmetry arising from a generally unequal assignment of the relative costs of type I and type II errors committed in the course of gene selection. The optimal set S(*) is defined as a minimizer of the average asymmetric distance from an arbitrary set S to all sets in the collection F(k). The minimization problem can be solved explicitly, leading to a frequency criterion for the inclusion of each gene in the final set. The proposed method is tested by resampling from real microarray gene expression data with artificially introduced shifts in expression levels of pre-defined genes, thereby mimicking their differential expression.

  18. Identical parallel machine scheduling with nonlinear deterioration and multiple rate modifying activities

    Directory of Open Access Journals (Sweden)

    Ömer Öztürkoğlu

    2017-07-01

    Full Text Available This study focuses on identical parallel machine scheduling of jobs with deteriorating processing times and rate-modifying activities. We consider non linearly increasing processing times of jobs based on their position assignment. Rate modifying activities are also considered to recover the increase in processing times of jobs due to deterioration. We also propose heuristics algorithms that rely on ant colony optimization and simulated annealing algorithms to solve the problem with multiple RMAs in a reasonable amount of time. Finally, we show that ant colony optimization algorithm generates close optimal solutions and superior results than simulated annealing algorithm.

  19. 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...

  20. 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...

  1. 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...

  2. An adult case of multiple squamous papillomas of the trachea associated with human papilloma virus type 6.

    Science.gov (United States)

    Shibuya, Hideki; Kutomi, Tomoko; Kujime, Kosei; Hara, Kei; Hisada, Tetsuya

    2008-01-01

    A 72-year-old woman with primary biliary cirrhosis complained of dry cough and wheezing. Chest computed tomography showed a tumor arising from the posterior wall of the trachea. Bronchoscopic examination revealed that the tumor was cauliflower-like, with two small polypoid tumors. They were diagnosed as multiple squamous papillomas. The main tumor was recurrent and removed by repeated microwave coagulation therapy (MCT) through bronchoscopy, whereas the two polypoid tumors were likely to disappear spontaneously. Human papilloma virus (HPV) type 6 DNA was detected in the tumor by polymerase chain reaction (PCR) amplification, suggesting that this virus was the cause of her papillomas.

  3. Diffuse-Type Caroli Disease with Characteristic Central Dot Sign Complicated by Multiple Intrahepatic and Common Bile Duct Stones.

    Science.gov (United States)

    Hwang, Moon Joo; Kim, Tae Nyeun

    2017-07-01

    Caroli disease (CD) is a rare congenital malformation of the liver characterized by non-obstructive, segmental, cystic dilatation of the intrahepatic bile ducts (IHDs). The clinical course is usually asymptomatic for the first 5-20 years, and symptoms may seldom occur throughout the patient's life. Bile stagnation leads to recurrent episodes of cholangitis, stone formation, or liver abscesses, and biliary cirrhosis usually occurs years later. Here we report on a 42-year-old man diagnosed with diffuse-type CD with a characteristic central dot sign, who had multiple intrahepatic and common bile duct (CBD) stones. CBD stones were treated successfully with endoscopic retrograde cholangiopancreatography (ERCP).

  4. 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.

  5. 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.

  6. Effect of Two Types of Active Recovery on Fatigue and Climbing Performance

    Directory of Open Access Journals (Sweden)

    Pedro L. Valenzuela, Pedro de la Villa, Carmen Ferragut

    2015-12-01

    Full Text Available Performing intra-session recovery is important in rock climbing due to the multiple efforts that climbers are required to make in competitions, as well as repeated climbing trials that they carry out during training sessions. Active recovery has been shown to be a better option than passive recovery. However, the type of active recovery that should be done and the influence of the type and quantity of muscle mass activated are not clear. The aim of this study was to compare the effects of recovering with easy climbing (CR or walking (WR on markers of fatigue and climbing performance. For this purpose, 14 subjects participated in this randomly assigned crossover protocol completing three two-minute climbing trials separated by two minutes of active recovery with the assigned method. Seven days later participants carried out the same protocol with the other recovery method. Blood lactate (La-, rating of perceived exertion (RPE, and heart rate (HR were analyzed as markers of fatigue and recovery, while meters climbed (MC and handgrip force (HF were analyzed for performance. La- values before the last climbing trial (p < 0.05; d = 0.69 and Peak La- values (p < 0.05; d = 0.77 were lower for CR than for WR. Climbers were able to ascend more meters in the set time when following the CR protocol (p < 0.01; d = 0.6, which shows the important role of the active recovery method carried out on climbing performance. There were no differences in HR, HF or RPE between protocols. A more sport-specific recovery protocol, in addition to moving great muscle mass (e.g. lower limbs, seems to enhance recovery and to facilitate lactate removal. For this reason, CR appears to be a more effective active recovery method than WR in sport rock climbing.

  7. 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.

  8. Inhibitory effect of rhubarb on intestinal α-glucosidase activity in type ...

    African Journals Online (AJOL)

    Keywords: Type 1 diabetes, α-Glucosidase activity, Acarbose®, Rhubarb, Postprandial glucose level ... intestinal absorption of carbohydrates [3]. Type 1 diabetes, which is caused by insulin deficiency ... novel drugs with high activity and low.

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. 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.

  14. Multiple contemporary arterial dissection in Ehlers-Danlos syndrome type IV

    Directory of Open Access Journals (Sweden)

    Anna Rocci

    2015-03-01

    Full Text Available We report a case of multiple spontaneous arteries dissection in a 52-year-old female; the patient had a relevant family history of vascular complications and typical features so we hypothesized vascular Ehlers-Danlos syndrome (EDS that was confirmed by genetic analysis of COL3A1 gene. We adopted a conservative approach: the patient was treated with heparin in the acute phase followed by aspirin and then celiprolol was started on the basis of a recent trial that demonstrates a reduction in arterial events in EDS patient treated. A careful follow-up was done with Doppler ultrasound and computed tomography scan, as non-invasive diagnostic techniques are preferred in these patients, and no other vascular symptomatic events have occurred. We tested all living relatives: half of them had COL3A1 mutation, they were referred to another center specialized in rare diseases and EDS for long-term follow-up and genetic counseling. This case demonstrates as a careful evaluation of clinical signs, clinical history of the patient and his family has allowed a definitive diagnosis, proper management of the patient during the acute event and in terms of prophylaxis of recurrence.

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Self-regulation as a type of managerial activity.

    Directory of Open Access Journals (Sweden)

    Anna Algazina

    2017-01-01

    Full Text Available УДК 342.9The subject. In the context of the ongoing administrative reform in the Russian Federation the issue of self-regulation is becoming increasingly important.Introduction of Institute of self-regulation is intended to reduce the degree of state intervention in private spheres of professional activity, to eliminate excessive administrative barriers, reduce government expenditures on regulation and control in their respective areas of operation, which is especially important in the current economic conditions.However, in Russian legal science is no recognized definition of "self-regulation", but a unity of views on the question of the relationship between self-regulation and state regulation of business relations.In this regard, the author attempts to examine the concept of "self-regulation" through the prism of knowledge about public administration.The purpose of the article is to identify the essential features and to articulate the concept of self-regulation by comparing it with other varieties of regulation.Methodology. The methodological basis for the study: general scientific methods (analysis, synthesis, comparison, description; private and academic (interpretation, formal-legal.Results, scope. Based on the analysis allocated in the science of administrative law approaches to the system of public administration justifies the conclusion that the notion "regulation" is specific in relation to the generic concept of "management" and is a kind of management, consisting in the drafting of rules of conduct and sanctions for non-compliance or inadequate performance.In addition, the article highlights the problem of the genesis of self-regulation, building a system of principles of self-regulation, comparison of varieties of self-regulatory organizations among themselves.Conclusions. The comparison of self-regulation other types of regulation (such as state regulation and co-regulation highlighted the essential features of this phenomenon

  1. 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.

  2. 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.

  3. 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...

  4. Multiple-type human papillomavirus (HPV) infections: a cross-sectional analysis of the prevalence of specific types in 309,000 women referred for HPV testing at the time of cervical cytology.

    Science.gov (United States)

    Dickson, Elizabeth Louise; Vogel, Rachel Isaksson; Bliss, Robin L; Downs, Levi S

    2013-09-01

    To determine the frequency of multiple-type cervical human papillomavirus (HPV) infections, and whether any types are involved in multiple-type infections more or less frequently than might be expected if these infections occur randomly. In this retrospective analysis of type-specific HPV testing, results from women 18 to 65 years old with samples collected between July 2007 and May 2011 were considered.Multivariate logistic regression analysis was used to model the presence of each of the 24 most prevalent HPV types, adjusting for one other HPV type, age, laboratory region, and age-by-region interactions. Human papillomavirus infection was present in 74,543 (24.1%) of 309,471 women and 65,492 (21.1%) were positive for one of the top 24 most prevalent HPV types. The most common HPV type was type 16, occurring in 4.1% of the entire sample. A total of 14,181 women were positive for 2 or more HPV types (4.6% of entire sample and 19.0% of HPV-positive sample). Two-way HPV type comparisons were analyzed. Types 52, 53, 81, and 83 were more likely to occur in multiple infections with other types; and types 16, 58, and 66 were less likely to occur in multiple infections with other types. Human papillomavirus types 72 and 81 have the strongest positive relationship (odds ratio, 5.2; 95% confidence interval, 3.6-7.4). Human papillomavirus types 33 and 66 have the strongest negative relationship (odds ratio, 0.4; 95% confidence interval, 0.2-0.6). In this population, multiple-type HPV infections were present in 4.6% of all women. Our findings suggest that there may be both competitive and cooperative interactions between HPV types.

  5. Multiple Types of Memory and Everyday Functional Assessment in Older Adults.

    Science.gov (United States)

    Beaver, Jenna; Schmitter-Edgecombe, Maureen

    2017-06-01

    Current proxy measures for assessing everyday functioning (e.g., questionnaires, performance-based measures, and direct observation) show discrepancies in their rating of functional status. The present study investigated the relationship between multiple proxy measures of functional status and content memory (i.e., memory for information), temporal order memory, and prospective memory in an older adult sample. A total of 197 community-dwelling older adults who did (n = 45) or did not meet (n = 152) criteria for mild cognitive impairment (MCI), completed six different assessments of functional status (two questionnaires, two performance-based tasks, and two direct observation tasks) as well as experimental measures of content memory, prospective memory, and temporal order memory. After controlling for demographics and content memory, the temporal order and prospective memory measures explained a significant amount of variance in all proxy functional status measures. When all variables were entered into the regression analyses, content memory and prospective memory were found to be significant predictors of all measures of functional status, whereas temporal order memory was a significant predictor for the questionnaire and direct observation measures, but not performance-based measures. The results suggest that direct observation and questionnaire measures may be able to capture components of everyday functioning that require context and temporal sequencing abilities, such as multi-tasking, that are not as well captured in many current laboratory performance-based measures of functional status. Future research should aim to inform the development and use of maximally effective and valid proxy measures of functional ability.

  6. Advances in risk-oriented surgery for multiple endocrine neoplasia type 2.

    Science.gov (United States)

    Machens, Andreas; Dralle, Henning

    2017-09-07

    Genetic association studies hinge on definite clinical case definitions of the disease of interest. This is why more penetrant mutations were overrepresented in early multiple endocrine neoplasia 2 (MEN2) studies, whereas less penetrant mutations went underrepresented. Enrichment of genetic association studies with advanced disease may produce a flawed understanding of disease evolution, precipitating far-reaching surgical strategies like bilateral total adrenalectomy and 4-gland parathyroidectomy in MEN2. The insight into the natural course of the disease gleaned over the past 25 years caused a paradigm shift in MEN2: from the removal of target organs at the expense of greater operative morbidity to close biochemical surveillance and targeted resection of adrenal tumors and hyperplastic parathyroid glands. The lead time provided by early identification of asymptomatic MEN2 carriers under biochemical surveillance delimits a ''window of opportunity'', within which (i) pre-emptive total thyroidectomy alone is adequate, circumventing morbidity attendant to central node dissection; (ii) subtotal 'tissue-sparing' adrenalectomy is sufficient, trading the risk of steroid dependency for the risk of a second pheochromocytoma in the adrenal remnant; and (iii) parathyroidectomy is limited to enlarged glands, trading the risk of hypoparathyroidism for the risk of leaving behind hyperactive parathyroid glands. Future research should delineate further the mutation-specific, age-dependent penetrance of pheochromocytoma and primary hyperparathyroidism to refine the risk-oriented approach to MEN2. The sweeping changes in the management of MEN2 since the new millenium hold the hope that death and major morbidity from this uncommon disease, can be eliminated in our lifetime.

  7. Multiple-locus variable-number tandem repeat analysis for molecular typing of Aspergillus fumigatus

    Directory of Open Access Journals (Sweden)

    Chermette René

    2010-12-01

    Full Text Available Abstract Background Multiple-locus variable-number tandem repeat (VNTR analysis (MLVA is a prominent subtyping method to resolve closely related microbial isolates to provide information for establishing genetic patterns among isolates and to investigate disease outbreaks. The usefulness of MLVA was recently demonstrated for the avian major pathogen Chlamydophila psittaci. In the present study, we developed a similar method for another pathogen of birds: the filamentous fungus Aspergillus fumigatus. Results We selected 10 VNTR markers located on 4 different chromosomes (1, 5, 6 and 8 of A. fumigatus. These markers were tested with 57 unrelated isolates from different hosts or their environment (53 isolates from avian species in France, China or Morocco, 3 isolates from humans collected at CHU Henri Mondor hospital in France and the reference strain CBS 144.89. The Simpson index for individual markers ranged from 0.5771 to 0.8530. A combined loci index calculated with all the markers yielded an index of 0.9994. In a second step, the panel of 10 markers was used in different epidemiological situations and tested on 277 isolates, including 62 isolates from birds in Guangxi province in China, 95 isolates collected in two duck farms in France and 120 environmental isolates from a turkey hatchery in France. A database was created with the results of the present study http://minisatellites.u-psud.fr/MLVAnet/. Three major clusters of isolates were defined by using the graphing algorithm termed Minimum Spanning Tree (MST. The first cluster comprised most of the avian isolates collected in the two duck farms in France, the second cluster comprised most of the avian isolates collected in poultry farms in China and the third one comprised most of the isolates collected in the turkey hatchery in France. Conclusions MLVA displayed excellent discriminatory power. The method showed a good reproducibility. MST analysis revealed an interesting clustering with a

  8. 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.

  9. 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...

  10. Social cognitive predictors of physical activity in relapsing-remitting multiple sclerosis.

    Science.gov (United States)

    Suh, Yoojin; Joshi, Ina; Olsen, Conner; Motl, Robert W

    2014-12-01

    Persons with relapsing-remitting multiple sclerosis (RRMS) are often sedentary, despite the benefits of the regular physical activity. This has motivated the search for variables that act as determinants of physical activity. Such variables are derived from theory and presumably represent targets of behavioral interventions for increasing physical activity. This prospective, observational study examined variables from social cognitive theory as determinants of physical activity 6 weeks later in persons with RRMS. Persons (N = 68) with RRMS initially completed a questionnaire battery that included measures of self-efficacy, physical, social, and self-evaluative outcome expectations, functional limitations as an impediment, social support as a facilitator, and goal setting for physical activity. The participants wore an accelerometer and completed a self-reported physical activity measure 6 weeks later. Data were analyzed using path analysis in Mplus 3.0. Self-efficacy (path coefficient = 0.19, p path coefficient = -0.33, p goal setting (path coefficient = 0.26, p path coefficient = 0.12, p goal setting (path coefficient = 0.02, p = 0.66). This model explained 28 % of the variance in physical activity. This prospective study suggests that self-efficacy, functional limitations, and goal setting might represent modifiable targets of behavioral interventions for increasing physical activity among persons with RRMS.

  11. 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

  12. 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

  13. 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.

  14. Statistical methods for integrating multiple types of high-throughput data.

    Science.gov (United States)

    Xie, Yang; Ahn, Chul

    2010-01-01

    Large-scale sequencing, copy number, mRNA, and protein data have given great promise to the biomedical research, while posing great challenges to data management and data analysis. Integrating different types of high-throughput data from diverse sources can increase the statistical power of data analysis and provide deeper biological understanding. This chapter uses two biomedical research examples to illustrate why there is an urgent need to develop reliable and robust methods for integrating the heterogeneous data. We then introduce and review some recently developed statistical methods for integrative analysis for both statistical inference and classification purposes. Finally, we present some useful public access databases and program code to facilitate the integrative analysis in practice.

  15. 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.

  16. 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.)

  17. Insulin pump therapy, multiple daily injections, and cardiovascular mortality in 18,168 people with type 1 diabetes: observational study.

    Science.gov (United States)

    Steineck, Isabelle; Cederholm, Jan; Eliasson, Björn; Rawshani, Araz; Eeg-Olofsson, Katarina; Svensson, Ann-Marie; Zethelius, Björn; Avdic, Tarik; Landin-Olsson, Mona; Jendle, Johan; Gudbjörnsdóttir, Soffia

    2015-06-22

    To investigate the long term effects of continuous subcutaneous insulin infusion (insulin pump therapy) on cardiovascular diseases and mortality in people with type 1 diabetes. Observational study. Swedish National Diabetes Register, Sweden 2005-12. 18,168 people with type 1 diabetes, 2441 using insulin pump therapy and 15,727 using multiple daily insulin injections. Cox regression analysis was used to estimate hazard ratios for the outcomes, with stratification of propensity scores including clinical characteristics, risk factors for cardiovascular disease, treatments, and previous diseases. Follow-up was for a mean of 6.8 years until December 2012, with 114,135 person years. With multiple daily injections as reference, the adjusted hazard ratios for insulin pump treatment were significantly lower: 0.55 (95% confidence interval 0.36 to 0.83) for fatal coronary heart disease, 0.58 (0.40 to 0.85) for fatal cardiovascular disease (coronary heart disease or stroke), and 0.73 (0.58 to 0.92) for all cause mortality. Hazard ratios were lower, but not significantly so, for fatal or non-fatal coronary heart disease and fatal or non-fatal cardiovascular disease. Unadjusted absolute differences were 3.0 events of fatal coronary heart disease per 1000 person years; corresponding figures were 3.3 for fatal cardiovascular disease and 5.7 for all cause mortality. When lower body mass index and previous cardiovascular diseases were excluded, results of subgroup analyses were similar to the results from complete data. A sensitivity analysis of unmeasured confounders in all individuals showed that an unmeasured confounders with hazard ratio of 1.3 would have to be present in >80% of the individuals treated with multiple daily injections versus not presence in those treated with pump therapy to invalidate the significantly lower hazard ratios for fatal cardiovascular disease. Data on patient education and frequency of blood glucose monitoring were missing, which might have

  18. Insulin pump therapy, multiple daily injections, and cardiovascular mortality in 18 168 people with type 1 diabetes: observational study

    Science.gov (United States)

    Cederholm, Jan; Eliasson, Björn; Rawshani, Araz; Eeg-Olofsson, Katarina; Svensson, Ann-Marie; Zethelius, Björn; Avdic, Tarik; Landin-Olsson, Mona; Jendle, Johan; Gudbjörnsdóttir, Soffia

    2015-01-01

    Objective To investigate the long term effects of continuous subcutaneous insulin infusion (insulin pump therapy) on cardiovascular diseases and mortality in people with type 1 diabetes. Design Observational study. Setting Swedish National Diabetes Register, Sweden 2005-12. Participants 18 168 people with type 1 diabetes, 2441 using insulin pump therapy and 15 727 using multiple daily insulin injections. Main outcome measures Cox regression analysis was used to estimate hazard ratios for the outcomes, with stratification of propensity scores including clinical characteristics, risk factors for cardiovascular disease, treatments, and previous diseases. Results Follow-up was for a mean of 6.8 years until December 2012, with 114 135 person years. With multiple daily injections as reference, the adjusted hazard ratios for insulin pump treatment were significantly lower: 0.55 (95% confidence interval 0.36 to 0.83) for fatal coronary heart disease, 0.58 (0.40 to 0.85) for fatal cardiovascular disease (coronary heart disease or stroke), and 0.73 (0.58 to 0.92) for all cause mortality. Hazard ratios were lower, but not significantly so, for fatal or non-fatal coronary heart disease and fatal or non-fatal cardiovascular disease. Unadjusted absolute differences were 3.0 events of fatal coronary heart disease per 1000 person years; corresponding figures were 3.3 for fatal cardiovascular disease and 5.7 for all cause mortality. When lower body mass index and previous cardiovascular diseases were excluded, results of subgroup analyses were similar to the results from complete data. A sensitivity analysis of unmeasured confounders in all individuals showed that an unmeasured confounders with hazard ratio of 1.3 would have to be present in >80% of the individuals treated with multiple daily injections versus not presence in those treated with pump therapy to invalidate the significantly lower hazard ratios for fatal cardiovascular disease. Data on patient education and

  19. 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

  20. 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.

  1. 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

  2. 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.

  3. 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.

  4. 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.

  5. 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 ...

  6. 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.

  7. Multiple Myeloma

    Science.gov (United States)

    Multiple myeloma is a cancer that begins in plasma cells, a type of white blood cell. These cells ... bones. No one knows the exact causes of multiple myeloma, but it is more common in older people ...

  8. Multiple human papillomavirus infections and type-competition in women from a clinic attendee population in China.

    Science.gov (United States)

    Nie, Jianhui; Liu, Jianhua; Xie, Hui; Sun, Zhengrong; Zhao, Juan; Chen, Qingqing; Liu, Yangyang; Huang, Weijin; Ruan, Qiang; Wang, Youchun

    2016-11-01

    To investigate the multi-infection patterns and type competition for human papillomavirus (HPV) in Chinese clinic attending women and evaluate the association between the infection status and cancer risk. Three hundred and thirty-two HPV-DNA-positive samples were genotyped for 21 HPVs and tested for 13 types of HPV neutralizing antibody using pseudoviron-based assay. Odds ratios (ORs) were calculated to evaluate the coinfection patterns for both DNA and neutralizing antibody (NAb), and the associations of HSIL+ with HPV DNA and NAb. Of the 332 HPV-DNA-positive subjects, 279 (84.0%) were detected as NAb positive. Multi-positive results were identified in 23.2% (77/332) HPV DNA tests and 60.2% (168/279) HPV NAb assays. The NAb titers for the multiple-positive samples (geometric mean 214) were significantly higher than the single-positive samples (geometric mean 114) (P < 0.01). HPV16-HPV52 was identified as a type-competition pair for both HPV DNA (OR = 0.09; 95%CI = 0.02-0.42) and NAb (OR = 0.27; 95%CI = 0.11-0.69) data. Compared to other types, HPV16 DNA was associated significantly with high risk of HSIL+ (OR = 2.57; 95%CI = 1.23-5.38). HPV16-HPV52 was identified as a potential type-competition pair, which might result in the type modulation with the implementation of the approved bi- or quadri-valent vaccines. J. Med. Virol. 88:1989-1998, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  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. Application of genetic algorithm - multiple linear regressions to predict the activity of RSK inhibitors

    Directory of Open Access Journals (Sweden)

    Avval Zhila Mohajeri

    2015-01-01

    Full Text Available This paper deals with developing a linear quantitative structure-activity relationship (QSAR model for predicting the RSK inhibition activity of some new compounds. A dataset consisting of 62 pyrazino [1,2-α] indole, diazepino [1,2-α] indole, and imidazole derivatives with known inhibitory activities was used. Multiple linear regressions (MLR technique combined with the stepwise (SW and the genetic algorithm (GA methods as variable selection tools was employed. For more checking stability, robustness and predictability of the proposed models, internal and external validation techniques were used. Comparison of the results obtained, indicate that the GA-MLR model is superior to the SW-MLR model and that it isapplicable for designing novel RSK inhibitors.

  11. Multiple Active Contours Guided by Differential Evolution for Medical Image Segmentation

    Directory of Open Access Journals (Sweden)

    I. Cruz-Aceves

    2013-01-01

    Full Text Available This paper presents a new image segmentation method based on multiple active contours guided by differential evolution, called MACDE. The segmentation method uses differential evolution over a polar coordinate system to increase the exploration and exploitation capabilities regarding the classical active contour model. To evaluate the performance of the proposed method, a set of synthetic images with complex objects, Gaussian noise, and deep concavities is introduced. Subsequently, MACDE is applied on datasets of sequential computed tomography and magnetic resonance images which contain the human heart and the human left ventricle, respectively. Finally, to obtain a quantitative and qualitative evaluation of the medical image segmentations compared to regions outlined by experts, a set of distance and similarity metrics has been adopted. According to the experimental results, MACDE outperforms the classical active contour model and the interactive Tseng method in terms of efficiency and robustness for obtaining the optimal control points and attains a high accuracy segmentation.

  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. 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.

  14. 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.

  15. Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) with multiple vascular complications misdiagnosed as Dubowitz syndrome.

    Science.gov (United States)

    Dieks, Jana-Katharina; Baumer, Alessandra; Wilichowski, Ekkehard; Rauch, Anita; Sigler, Matthias

    2014-09-01

    To date, the genetic basis of Dubowitz syndrome (short stature, microcephaly, facial abnormalities, eczema) is unknown and vascular complications are not known to be associated with this syndrome. In microcephalic osteodysplastic primordial dwarfism type II (MOPD II; disproportionate short statue, microcephaly, facial abnormalities), however, cerebral aneurysms and other vascular abnormalities are frequent complications. MOPD II is a genetic disorder caused by mutations in the pericentrin (PCNT) gene (21q22). We report on a patient who came to our attention as a 22-year-old with subarachnoid bleeding due to a ruptured cranial aneurysm. Until then, the patient was thought and published to have Dubowitz syndrome; previously, he was treated with coronary bypass surgery for extensive coronary angiopathy. Consecutive genetic testing revealed MOPD II. After clinical stabilization, the patient was discharged to a specialized rehabilitation center where he died due to re-rupture of a cranial aneurysm. In patients with short stature-especially when clinical features are accompanied by vascular complications-MOPD II should be considered as a differential diagnosis leading to consecutive genetic testing. After detection of mutations in the PCNT gene, a full vascular status including cerebral imaging and cardiac evaluation needs to be determined in order to analyze vascular abnormalities and initiate prophylactic treatment.

  16. 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

  17. 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.

  18. 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.

  19. 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

    2015-01-01

    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. PMID:26350210

  20. Relationship Between Age, Experience, and Student Preference for Types of Learning Activities in Online Courses

    Directory of Open Access Journals (Sweden)

    Thomas A. Simonds

    2017-10-01

    Full Text Available In this study, two researchers explored student learning preferences in online courses. They used the scholarship of teaching and learning process as a research model, and embedded a web-based survey and online focus groups in the online courses they were teaching. After collecting data, the researchers conducted multiple logistic regression analyses to test their hypothesis that a relationship existed between some student factors and student preferences for types of online learning activities. The results of the data analysis revealed a statistically significant relationship between student age and student preference for certain types of online learning activities. Older students in the study indicated a much stronger preference for videos of the professor lecturing, while younger students tended to prefer more interactive learning strategies. Focus group comments from the older students provide insights into some of the reasons why they found watching video lectures to be helpful for their learning, and comments from younger students illustrate how they learn best in online courses. The researchers offer suggestions for online instructors based on the findings of this study, and they explain why online instructors may find the scholarship of teaching and learning research process especially helpful for both teaching and research efforts.

  1. 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.

  2. 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.

  3. 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

  4. Can Inner Experience Be Apprehended in High Fidelity? Examining Brain Activation and Experience from Multiple Perspectives

    Science.gov (United States)

    Hurlburt, Russell T.; Alderson-Day, Ben; Fernyhough, Charles; Kühn, Simone

    2017-01-01

    We discuss the historical context for explorations of “pristine inner experience,” attempts to apprehend and describe the inner experiences that directly present themselves in natural environments. There is no generally accepted method for determining whether such apprehensions/descriptions should be considered high fidelity. By analogy from musical recording, we present and discuss one strategy for establishing experiential fidelity: the examining of brain activation associated with a variety of experiential perspectives that had not been specified at the time of data collection. We beeped participants in an fMRI scanner at randomly-determined times and recorded time-locked brain activations. We used Descriptive Experience Sampling (DES) to apprehend and describe the participant's experience that was ongoing at each beep. These apprehensions/descriptions were obtained with no specific theoretical perspective or experimental intention when originally collected. If these apprehensions/descriptions were of high fidelity, then these pairings of moments of experience and brain activations should be able to be productively examined and re-examined in multiple ways and from multiple theoretical perspectives. We discuss a small set of such re-examinations and conclude that this strategy is worthy of further examination. PMID:28191000

  5. Can Inner Experience Be Apprehended in High Fidelity? Examining Brain Activation and Experience from Multiple Perspectives.

    Science.gov (United States)

    Hurlburt, Russell T; Alderson-Day, Ben; Fernyhough, Charles; Kühn, Simone

    2017-01-01

    We discuss the historical context for explorations of "pristine inner experience," attempts to apprehend and describe the inner experiences that directly present themselves in natural environments. There is no generally accepted method for determining whether such apprehensions/descriptions should be considered high fidelity. By analogy from musical recording, we present and discuss one strategy for establishing experiential fidelity: the examining of brain activation associated with a variety of experiential perspectives that had not been specified at the time of data collection. We beeped participants in an fMRI scanner at randomly-determined times and recorded time-locked brain activations. We used Descriptive Experience Sampling (DES) to apprehend and describe the participant's experience that was ongoing at each beep. These apprehensions/descriptions were obtained with no specific theoretical perspective or experimental intention when originally collected. If these apprehensions/descriptions were of high fidelity, then these pairings of moments of experience and brain activations should be able to be productively examined and re-examined in multiple ways and from multiple theoretical perspectives. We discuss a small set of such re-examinations and conclude that this strategy is worthy of further examination.

  6. 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.

  7. 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.

  8. Eye Typing using Markov and Active Appearance Models

    DEFF Research Database (Denmark)

    Hansen, Dan Witzner; Hansen, John Paulin; Nielsen, Mads

    2002-01-01

    We propose a non-intrusive eye tracking system intended for the use of everyday gaze typing using web cameras. We argue that high precision in gaze tracking is not needed for on-screen typing due to natural language redundancy. This facilitates the use of low-cost video components for advanced...

  9. 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.

  10. 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.

  11. 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.

  12. 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.

  13. Evidence of impaired brain activity balance after passive sensorimotor stimulation in multiple sclerosis.

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    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

  14. 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...

  15. 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.

  16. 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. Copyright © 2014. Published by Elsevier Ireland Ltd.

  17. 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

  18. Multiple source genes of HAmo SINE actively expanded and ongoing retroposition in cyprinid genomes relying on its partner LINE

    Directory of Open Access Journals (Sweden)

    Gan Xiaoni

    2010-04-01

    Full Text Available Abstract Background We recently characterized HAmo SINE and its partner LINE in silver carp and bighead carp based on hybridization capture of repetitive elements from digested genomic DNA in solution using a bead-probe 1. To reveal the distribution and evolutionary history of SINEs and LINEs in cyprinid genomes, we performed a multi-species search for HAmo SINE and its partner LINE using the bead-probe capture and internal-primer-SINE polymerase chain reaction (PCR techniques. Results Sixty-seven full-size and 125 internal-SINE sequences (as well as 34 full-size and 9 internal sequences previously reported in bighead carp and silver carp from 17 species of the family Cyprinidae were aligned as well as 14 new isolated HAmoL2 sequences. Four subfamilies (type I, II, III and IV, which were divided based on diagnostic nucleotides in the tRNA-unrelated region, expanded preferentially within a certain lineage or within the whole family of Cyprinidae as multiple active source genes. The copy numbers of HAmo SINEs were estimated to vary from 104 to 106 in cyprinid genomes by quantitative RT-PCR. Over one hundred type IV members were identified and characterized in the primitive cyprinid Danio rerio genome but only tens of sequences were found to be similar with type I, II and III since the type IV was the oldest subfamily and its members dispersed in almost all investigated cyprinid fishes. For determining the taxonomic distribution of HAmo SINE, inter-primer SINE PCR was conducted in other non-cyprinid fishes, the results shows that HAmo SINE- related sequences may disperse in other families of order Cypriniforms but absent in other orders of bony fishes: Siluriformes, Polypteriformes, Lepidosteiformes, Acipenseriformes and Osteoglossiforms. Conclusions Depending on HAmo LINE2, multiple source genes (subfamilies of HAmo SINE actively expanded and underwent retroposition in a certain lineage or within the whole family of Cyprinidae. From this

  19. 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

  20. Multiple Regression Analysis of the Variable Component in the Near-Infrared Region for Type 1 AGN MCG+08-11-011

    CERN Document Server

    Tomita, H; Kobayashi, Y; Minezaki, T; Enya, K; Suganuma, M; Aoki, T; Koshida, S; Yamauchi, M; Tomita, Hiroyuki; Yoshii, Yuzuru; Kobayashi, Yukiyasu; Minezaki, Takeo; Enya, Keigo; Suganuma, Masahiro; Aoki, Tsutomu; Koshida, Shintaro; Yamauchi, Masahiro

    2006-01-01

    We propose a new method of analysing a variable component for type 1 active galactic nuclei (AGNs) in the near-infrared wavelength region. This analysis uses a multiple regression technique and divides the variable component into two components originating in the accretion disk at the center of AGNs and from the dust torus that far surrounds the disk. Applying this analysis to the long-term $VHK$ monitoring data of MCG+08-11-011 that were obtained by the MAGNUM project, we found that the $(H-K)$-color temperature of the dust component is $T = 1635$K $\\pm20$K, which agrees with the sublimation temperature of dust grains, and that the time delay of $K$ to $H$ variations is $\\Delta t\\approx 6$ days, which indicates the existence of a radial temperature gradient in the dust torus. As for the disk component, we found that the power-law spectrum of $f_\