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Sample records for mrc rt01 isrctn47772397

  1. Assessing correlations between the spatial distribution of the dose to the rectal wall and late rectal toxicity after prostate radiotherapy: an analysis of data from the MRC RT01 trial (ISRCTN 47772397)

    NASA Astrophysics Data System (ADS)

    Buettner, Florian; Gulliford, Sarah L.; Webb, Steve; Sydes, Matthew R.; Dearnaley, David P.; Partridge, Mike

    2009-11-01

    Many studies have been performed to assess correlations between measures derived from dose-volume histograms and late rectal toxicities for radiotherapy of prostate cancer. The purpose of this study was to quantify correlations between measures describing the shape and location of the dose distribution and different outcomes. The dose to the rectal wall was projected on a two-dimensional map. In order to characterize the dose distribution, its centre of mass, longitudinal and lateral extent, and eccentricity were calculated at different dose levels. Furthermore, the dose-surface histogram (DSH) was determined. Correlations between these measures and seven clinically relevant rectal-toxicity endpoints were quantified by maximally selected standardized Wilcoxon rank statistics. The analysis was performed using data from the RT01 prostate radiotherapy trial. For some endpoints, the shape of the dose distribution is more strongly correlated with the outcome than simple DSHs. Rectal bleeding was most strongly correlated with the lateral extent of the dose distribution. For loose stools, the strongest correlations were found for longitudinal extent; proctitis was most strongly correlated with DSH. For the other endpoints no statistically significant correlations could be found. The strengths of the correlations between the shape of the dose distribution and outcome differed considerably between the different endpoints. Due to these significant correlations, it is desirable to use shape-based tools in order to assess the quality of a dose distribution.

  2. Dose-Volume Constraints to Reduce Rectal Side Effects From Prostate Radiotherapy: Evidence From MRC RT01 Trial ISRCTN 47772397

    SciTech Connect

    Gulliford, Sarah L.; Foo, Kerwyn; Morgan, Rachel C.; Aird, Edwin G.; Bidmead, A. Margaret; Critchley, Helen; Evans, Philip M. D.Phil.; Gianolini, Stefano; Mayles, W. Philip; Moore, A. Rollo; Sanchez-Nieto, Beatriz; Partridge, Mike; Sydes, Matthew R. C.Stat; Webb, Steve; Dearnaley, David P.

    2010-03-01

    Purpose: Radical radiotherapy for prostate cancer is effective but dose limited because of the proximity of normal tissues. Comprehensive dose-volume analysis of the incidence of clinically relevant late rectal toxicities could indicate how the dose to the rectum should be constrained. Previous emphasis has been on constraining the mid-to-high dose range (>=50 Gy). Evidence is emerging that lower doses could also be important. Methods and Materials: Data from a large multicenter randomized trial were used to investigate the correlation between seven clinically relevant rectal toxicity endpoints (including patient- and clinician-reported outcomes) and an absolute 5% increase in the volume of rectum receiving the specified doses. The results were quantified using odds ratios. Rectal dose-volume constraints were applied retrospectively to investigate the association of constraints with the incidence of late rectal toxicity. Results: A statistically significant dose-volume response was observed for six of the seven endpoints for at least one of the dose levels tested in the range of 30-70 Gy. Statistically significant reductions in the incidence of these late rectal toxicities were observed for the group of patients whose treatment plans met specific proposed dose-volume constraints. The incidence of moderate/severe toxicity (any endpoint) decreased incrementally for patients whose treatment plans met increasing numbers of dose-volume constraints from the set of V30<=80%, V40<=65%, V50<=55%, V60<=40%, V65<=30%, V70<=15%, and V75<=3%. Conclusion: Considering the entire dose distribution to the rectum by applying dose-volume constraints such as those tested here in the present will reduce the incidence of late rectal toxicity.

  3. Combining Dosimetry & Toxicity: Analysis of two UK Phase III Clinical trials

    NASA Astrophysics Data System (ADS)

    Gulliford, Sarah L.

    2014-03-01

    There are many advantages to performing a clinical trial when implementing a novel radiotherapy technique. The clinical trials framework enables the safety and efficacy of the "experimental arm" to be tested and ensures practical support, rigorous quality control and data monitoring for participating centres. In addition to the clinical and follow-up data collected from patients within the trial, it is also possible to collect 3-D dosimetric information from the corresponding radiotherapy treatment plans. Analysing the combination of dosimetric, clinical and follow-up data enhances the understanding of the relationship between the dose delivered to both the target and normal tissue structures and reported outcomes & toxicity. Aspects of the collection, collation and analysis of data from two UK multicentre Phase III radiotherapy trials are presented here. MRC-RT01 dose-escalation prostate radiotherapy trial ISRCTN47772397 was one of the first UK multi-centre radiotherapy trials to collect 3-D dosimetric data. A number of different analysis methodologies were implemented to investigate the relationship between the dose distribution to the rectum and specific rectal toxicities. More recently data was collected from the PARSPORT trial (Parotid Sparing IMRT vs conventional head and neck radiotherapy) ISRCTN48243537. In addition to the planned analysis, dosimetric analysis was employed to investigate an unexpected finding that acute fatigue was more prevalent in the IMRT arm of the trial. It can be challenging to collect 3-D dosimetric information from multicentre radiotherapy trials. However, analysing the relationship between dosimetric and toxicity data provides invaluable information which can influence the next generation of radiotherapy techniques.

  4. MRC2014: Extensions to the MRC format header for electron cryo-microscopy and tomography

    PubMed Central

    Cheng, Anchi; Henderson, Richard; Mastronarde, David; Ludtke, Steven J.; Schoenmakers, Remco H.M.; Short, Judith; Marabini, Roberto; Dallakyan, Sargis; Agard, David; Winn, Martyn

    2015-01-01

    The MRC binary file format is widely used in the three-dimensional electron microscopy field for storing image and volume data. Files contain a header which describes the kind of data held, together with other important metadata. In response to advances in electron microscopy techniques, a number of variants to the file format have emerged which contain useful additional data, but which limit interoperability between different software packages. Following extensive discussions, the authors, who represent leading software packages in the field, propose a set of extensions to the MRC format standard designed to accommodate these variants, while restoring interoperability. The MRC format is equivalent to the map format used in the CCP4 suite for macromolecular crystallography, and the proposal also maintains interoperability with crystallography software. This Technical Note describes the proposed extensions, and serves as a reference for the standard. PMID:25882513

  5. MRC2014: Extensions to the MRC format header for electron cryo-microscopy and tomography.

    PubMed

    Cheng, Anchi; Henderson, Richard; Mastronarde, David; Ludtke, Steven J; Schoenmakers, Remco H M; Short, Judith; Marabini, Roberto; Dallakyan, Sargis; Agard, David; Winn, Martyn

    2015-11-01

    The MRC binary file format is widely used in the three-dimensional electron microscopy field for storing image and volume data. Files contain a header which describes the kind of data held, together with other important metadata. In response to advances in electron microscopy techniques, a number of variants to the file format have emerged which contain useful additional data, but which limit interoperability between different software packages. Following extensive discussions, the authors, who represent leading software packages in the field, propose a set of extensions to the MRC format standard designed to accommodate these variants, while restoring interoperability. The MRC format is equivalent to the map format used in the CCP4 suite for macromolecular crystallography, and the proposal also maintains interoperability with crystallography software. This Technical Note describes the proposed extensions, and serves as a reference for the standard. PMID:25882513

  6. A new method of ICCD imaging system MRC measurement

    NASA Astrophysics Data System (ADS)

    Li, Sheng-cai; Jin, Wei-qi; Wang, Xia; Zhang, Wei-qiang; Dong, Hai-yan

    2005-02-01

    Based on analysis of the working principle of ICCD imaging system, the paper develops a new testing system for synthetic performance of ICCD imaging system. With the help of this testing system for integrative performance and the theory of Weibull psychometric function, a new method for MRC measurement of Space Light Modulation (SLM) is proposed, and the paper firstly implements measurement for minimum resolvable contrast performance of ICCD imaging system. The method provides reference for MRC performance measurement of other imaging system.

  7. Advanced non-disruptive manufacturing rule checks (MRC)

    NASA Astrophysics Data System (ADS)

    Moore, Bill; Do, Tanya; Morgan, Ray E.

    2006-10-01

    New advanced mask rule checking (MRC) solutions are required to ensure cost effective, high yield photomask manufacturing processes at 65nm and below and are needed to provide new verification capabilities for mask makers and data prep engineers alike. Traditional MRC, which implements fundamental geometric data checks on limited data formats, is not sufficient for advanced photomask manufacturing. Like recent advances in design rule checking (DRC) software, which includes extensive "manufacturing-aware" rules (or DFM rules), MRC solutions must evolve to include a more comprehensive and intelligent rule checks for the mask manufacturing process. This paper describes the development and testing of an advanced MRC software solution developed within the CATS TM mask data preparation (MDP) solution from Synopsys Inc. The new MRC solution enables the inspection and analysis of mask layout patterns for simple and advanced data verification checks. Proposed applications for mask data prep applications are discussed and include incoming design verification, fracture data correction, inspection tool data tags, mask manufacturing tool or inspection tool selection, and job deck verification.

  8. Constrained-transport Hall-MHD simulations using CWENO reconstruction with libMRC

    NASA Astrophysics Data System (ADS)

    Lin, Liwei; Germaschewski, Kai; Abbott, Stephen; Maynard, Kris; Raeder, Jimmy

    2013-10-01

    We present a new CWENO (Centrally-Weighted Essentially Non-Oscillatory) reconstruction based extended MHD (XMHD) solver that has been built for libMRC. libMRC is a library for creating efficient parallel PDE solvers on structured grids, which is used in the MRC (Magnetic Reconnection Code), OpenGGCM (Open Global Geospace Circulation Model) and PSC (Plasma Simulation Code) codes. The use of libMRC gives us access to its core functionality of providing an automated code generation framework which takes a user provided PDE right hand side in symbolic form to generate an efficient, computer-architecture specific, parallel code. libMRC also supports block-structured adaptive mesh refinement, and implicit-time stepping through integration with the PETSc library. We demonstrate validation of the new CWENO MHD solver against existing solvers both in standard test problems as well as in 3D global magnetosphere simulations.

  9. Differences in physical activity according to mMRC grade in patients with COPD

    PubMed Central

    Hayata, Atsushi; Minakata, Yoshiaki; Matsunaga, Kazuto; Nakanishi, Masanori; Yamamoto, Nobuyuki

    2016-01-01

    Background Physical activity (PA) is impaired from the early stages of COPD, is associated with a worsening of disease prognosis, and causes COPD patients to restrict their daily activities in order to avoid breathlessness. The development of a simple tool to estimate physical activity level (PAL) could be useful for the management of COPD. Objectives We investigated the differences in PA according to the modified Medical Research Council (mMRC) grade in patients with COPD. Methods A cross-sectional study was performed on stable outpatients with COPD. PA was measured for 2 weeks using a triaxial accelerometer, and dyspnea grade was evaluated in all patients using the mMRC scale. Results Ninety-eight patients were recruited. Significant differences in PA duration were observed at all intensities according to the mMRC grade. Despite treatment with controller medications, 59.2% of COPD patients had low PAL, which was <1.5 metabolic equivalents multiplied by hour per day. COPD patients with an mMRC grade ≥2, which was the most balanced cutoff point in the receiver operating characteristic curve, showed a higher reduction rate of PAL (80.0% at mMRC grade 2, 71.4% at mMRC grade 3, and 100% at mMRC grade 4). Conclusion PA differed according to the mMRC grade, and mMRC grade ≥2 could predict a low PAL. Therefore, assessment of breathlessness by the mMRC questionnaire would be useful to stratify the risks of reduced PA in COPD.

  10. Differences in physical activity according to mMRC grade in patients with COPD

    PubMed Central

    Hayata, Atsushi; Minakata, Yoshiaki; Matsunaga, Kazuto; Nakanishi, Masanori; Yamamoto, Nobuyuki

    2016-01-01

    Background Physical activity (PA) is impaired from the early stages of COPD, is associated with a worsening of disease prognosis, and causes COPD patients to restrict their daily activities in order to avoid breathlessness. The development of a simple tool to estimate physical activity level (PAL) could be useful for the management of COPD. Objectives We investigated the differences in PA according to the modified Medical Research Council (mMRC) grade in patients with COPD. Methods A cross-sectional study was performed on stable outpatients with COPD. PA was measured for 2 weeks using a triaxial accelerometer, and dyspnea grade was evaluated in all patients using the mMRC scale. Results Ninety-eight patients were recruited. Significant differences in PA duration were observed at all intensities according to the mMRC grade. Despite treatment with controller medications, 59.2% of COPD patients had low PAL, which was <1.5 metabolic equivalents multiplied by hour per day. COPD patients with an mMRC grade ≥2, which was the most balanced cutoff point in the receiver operating characteristic curve, showed a higher reduction rate of PAL (80.0% at mMRC grade 2, 71.4% at mMRC grade 3, and 100% at mMRC grade 4). Conclusion PA differed according to the mMRC grade, and mMRC grade ≥2 could predict a low PAL. Therefore, assessment of breathlessness by the mMRC questionnaire would be useful to stratify the risks of reduced PA in COPD. PMID:27695306

  11. MRC 1925-296: a new WAT in a Poor Cluster

    NASA Astrophysics Data System (ADS)

    Oozeer, N.; Somanah, R.

    2010-10-01

    We have observed MRC 1925-296 using the Giant Metre Wave Radio Telescope (GMRT) at 618 MHz. We classify MRC 1925-296 as a Wide Angle Tail (WAT) source with a rather asymmetric morphology in extent with respect to the radio core. The host galaxy of MRC 1925-296 is coincident with an E+4 galaxy (ESO460-004) of r magnitude 13.83, with a redshift of 0.02442. Using multi-wavelength data, we derive physical properties of the source.

  12. Reconstitution of Rad53 Activation by Mec1 through Adaptor Protein Mrc1*

    PubMed Central

    Chen, Sheng-hong; Zhou, Huilin

    2009-01-01

    Upon DNA replication stress, stalled DNA replication forks serve as a platform to recruit many signaling proteins, leading to the activation of the DNA replication checkpoint. Activation of Rad53, a key effector kinase in the budding yeast Saccharomyces cerevisiae, is essential for stabilizing DNA replication forks during replication stress. Using an activity-based assay for Rad53, we found that Mrc1, a replication fork-associated protein, cooperates with Mec1 to activate Rad53 directly. Reconstitution of Rad53 activation using purified Mec1 and Mrc1 showed that the addition of Mrc1 stimulated a more than 70-fold increase in the ability of Mec1 to activate Rad53. Instead of increasing the catalytic activity of Mec1, Mrc1 was found to facilitate the phosphorylation of Rad53 by Mec1 via promotion of a stronger enzyme-substrate interaction between them. Further, the conserved C-terminal domain of Mrc1 was found to be required for Rad53 activation. These results thus provide insights into the role of the adaptor protein Mrc1 in activating Rad53 in the DNA replication checkpoint. PMID:19457865

  13. The DNA-Binding Domain of S. pombe Mrc1 (Claspin) Acts to Enhance Stalling at Replication Barriers.

    PubMed

    Zech, Juergen; Godfrey, Emma Louise; Masai, Hisao; Hartsuiker, Edgar; Dalgaard, Jacob Zeuthen

    2015-01-01

    During S-phase replication forks can stall at specific genetic loci. At some loci, the stalling events depend on the replisome components Schizosaccharomyces pombe Swi1 (Saccharomyces cerevisiae Tof1) and Swi3 (S. cerevisiae Csm3) as well as factors that bind DNA in a site-specific manner. Using a new genetic screen we identified Mrc1 (S. cerevisiae Mrc1/metazoan Claspin) as a replisome component involved in replication stalling. Mrc1 is known to form a sub-complex with Swi1 and Swi3 within the replisome and is required for the intra-S phase checkpoint activation. This discovery is surprising as several studies show that S. cerevisiae Mrc1 is not required for replication barrier activity. In contrast, we show that deletion of S. pombe mrc1 leads to an approximately three-fold reduction in barrier activity at several barriers and that Mrc1's role in replication fork stalling is independent of its role in checkpoint activation. Instead, S. pombe Mrc1 mediated fork stalling requires the presence of a functional copy of its phylogenetically conserved DNA binding domain. Interestingly, this domain is on the sequence level absent from S. cerevisiae Mrc1. Our study indicates that direct interactions between the eukaryotic replisome and the DNA are important for site-specific replication stalling.

  14. Advanced manufacturing rules check (MRC) for fully automated assessment of complex reticle designs: Part II

    NASA Astrophysics Data System (ADS)

    Straub, J. A.; Aguilar, D.; Buck, P. D.; Dawkins, D.; Gladhill, R.; Nolke, S.; Riddick, J.

    2006-10-01

    Advanced electronic design automation (EDA) tools, with their simulation, modeling, design rule checking, and optical proximity correction capabilities, have facilitated the improvement of first pass wafer yields. While the data produced by these tools may have been processed for optimal wafer manufacturing, it is possible for the same data to be far from ideal for photomask manufacturing, particularly at lithography and inspection stages, resulting in production delays and increased costs. The same EDA tools used to produce the data can be used to detect potential problems for photomask manufacturing in the data. In the previous paper, it was shown how photomask MRC is used to uncover data related problems prior to automated defect inspection. It was demonstrated how jobs which are likely to have problems at inspection could be identified and separated from those which are not. The use of photomask MRC in production was shown to reduce time lost to aborted runs and troubleshooting due to data issues. In this paper, the effectiveness of this photomask MRC program in a high volume photomask factory over the course of a year as applied to more than ten thousand jobs will be shown. Statistics on the results of the MRC runs will be presented along with the associated impact to the automated defect inspection process. Common design problems will be shown as well as their impact to mask manufacturing throughput and productivity. Finally, solutions to the most common and most severe problems will be offered and discussed.

  15. High Genetic Stability of Dengue Virus Propagated in MRC-5 Cells as Compared to the Virus Propagated in Vero Cells

    PubMed Central

    Butler, Michael; Wu, Suh-Chin

    2008-01-01

    This work investigated the replication kinetics of the four dengue virus serotypes (DEN-1 to DEN-4), including dengue virus type 4 (DEN-4) recovered from an infectious cDNA clone, in Vero cells and in MRC-5 cells grown on Cytodex 1 microcarriers. DEN-1 strain Hawaii, DEN-2 strain NGC, DEN-3 strain H-87, and DEN-4 strain H-241 , and DEN-4 strain 814669 derived from cloned DNA, were used to infect Vero cells and MRC-5 cells grown in serum-free or serum-containing microcarrier cultures. Serum-free and serum-containing cultures were found to yield comparable titers of these viruses. The cloned DNA-derived DEN-4 started genetically more homogeneous was used to investigate the genetic stability of the virus propagated in Vero cells and MRC-5 cells. Sequence analysis revealed that the DEN-4 propagated in MRC-5 cells maintained a high genetic stability, compared to the virus propagated in Vero cells. Amino acid substitutions of Gly104Cys and Phe108Ile were detected at 70%, 60%, respectively, in the envelope (E) protein of DEN-4 propagated in Vero cells, whereas a single mutation of Glu345Lys was detected at 50% in E of the virus propagated in MRC-5 cells. Sequencing of multiple clones of three separate DNA fragments spanning 40% of the genome also indicated that DEN-4 propagated in Vero cells contained a higher number of mutations than the virus growing in MRC-5 cells. Although Vero cells yielded a peak virus titer approximately 1 to 17 folds higher than MRC-5 cells, cloned DEN-4 from MRC-5 cells maintained a greater stability than the virus from Vero cells. Serum-free microcarrier cultures of MRC-5 cells offer a potentially valuable system for the large-scale production of live-attenuated DEN vaccines. PMID:18350148

  16. ROS-dependent HMGA2 upregulation mediates Cd-induced proliferation in MRC-5 cells.

    PubMed

    Xie, Huaying; Wang, Jiayue; Jiang, Liping; Geng, Chengyan; Li, Qiujuan; Mei, Dan; Zhao, Lian; Cao, Jun

    2016-08-01

    Cadmium (Cd) is a heavy metal widely found in a number of environmental matrices, and the exposure to Cd is increasing nowadays. In this study, the role of high mobility group A2 (HMGA2) in Cd-induced proliferation was investigated in MRC-5 cells. Exposure to Cd (2μM) for 48h significantly enhanced the growth of MRC-5 cells, increased reactive oxygen species (ROS) production, and induced both mRNA and protein expression of HMGA2. Evidence for Cd-induced reduction of the number of G0/G1 phase cells and an increase in the number of cells in S phase and G2/M phase was sought by flow cytometric analysis. Western blot analysis showed that cyclin D1, cyclin B1, and cyclin E were upregulated in Cd-treated cells. Further study revealed that N-acetyl cysteine (NAC) markedly prevented Cd-induced proliferation of MRC-5 cells, ROS generation, and the increasing protein level of HMGA2. Silencing of HMGA2 gene by siRNA blocked Cd-induced cyclin D1, cyclin B1, and cyclin E expression and reduction of the number of G0/G1 phase cells. Combining, our data showed that Cd-induced ROS formation provoked HMGA2 upregulation, caused cell cycle changes, and led to cell proliferation. This suggests that HMGA2 might be an important biomarker in Cd-induced cell proliferation.

  17. Thymic Stromal Lymphopoietin Promotes Fibrosis and Activates Mitogen-Activated Protein Kinases in MRC-5 Cells

    PubMed Central

    Li, Li; Tang, Su; Tang, Xiaodong

    2016-01-01

    Background Acute lung injury (ALI) is a life-threatening hypoxemic respiratory disorder with high incidence and mortality. ALI usually manifests as widespread inflammation and lung fibrosis with the accumulation of pro-inflammatory and pro-fibrotic factors and collagen. Thymic stromal lymphopoietin (TSLP) has a significant role in regulation of inflammation but little is known about its roles in lung fibrosis or ALI. This study aimed to define the role and possible regulatory mechanism of TSLP in lung fibrosis. Material/Methods We cultured human lung fibroblast MRC-5 cells and overexpressed or inhibited TSLP by the vector or small interfering RNA transfection. Then, the pro-fibrotic factors skeletal muscle actin alpha (α-SMA) and collagen I, and the 4 mitogen-activated protein kinases (MAPKs) – MAPK7, p38, extracellular signal-regulated kinase 1 (ERK1), and c-Jun N-terminal kinase 1 (JNK1) – were detected by Western blot. Results Results showed that TSLP promoted the production of α-SMA and collagen I (P<0.001), suggesting that it can accelerate MRC-5 cell fibrosis. It also activated the expression of MAPK7, p-p38, p-ERK1, and p-JNK1, but the total MAPK7, p-38, ERK1, and JNK1 protein levels were mostly unchanged, indicating the activated MAPK pathways that might contribute to the promotion of cell fibrosis. Conclusions This study shows the pro-fibrotic role of TSLP in MRC-5 cells, suggesting TSLP is a potential therapeutic target for treating lung fibrosis in ALI. It possibly functions via activating MAPKs. These findings add to our understanding of the mechanism of fibrosis. PMID:27385084

  18. Preparation and immunogenicity of vaccine Ac NFU1 (S-) MRC towards the prevention of herpes genitalis.

    PubMed Central

    Skinner, G R; Woodman, C B; Hartley, C E; Buchan, A; Fuller, A; Durham, J; Synnott, M; Clay, J C; Melling, J; Wiblin, C; Wilkins, J

    1982-01-01

    A subunit antigenoid vaccine, Ac NFU1 (S-) MRC, was used to prevent primary herpes genitalis in 60 subjects considered to be at risk of this infection. There was no evidence of serious local or general side effects. Neutralising antibody responses were detected in 59% and 90% of subjects receiving the low and high doses of vaccine respectively; immunoprecipitating antibody was detected at a lower frequency, namely in 23% and 43% of subjects receiving the low and high doses respectively. After a mean follow-up period of 18 months none of the vaccinated subjects contracted herpes genitalis after completing the vaccination course. Images PMID:6293640

  19. The Replisome-Coupled E3 Ubiquitin Ligase Rtt101Mms22 Counteracts Mrc1 Function to Tolerate Genotoxic Stress

    PubMed Central

    Melnik, Andre; Wilson-Zbinden, Caroline; Schellhaas, René; Kastner, Lisa; Piwko, Wojciech; Dees, Martina; Picotti, Paola; Maric, Marija; Labib, Karim; Luke, Brian; Peter, Matthias

    2016-01-01

    Faithful DNA replication and repair requires the activity of cullin 4-based E3 ubiquitin ligases (CRL4), but the underlying mechanisms remain poorly understood. The budding yeast Cul4 homologue, Rtt101, in complex with the linker Mms1 and the putative substrate adaptor Mms22 promotes progression of replication forks through damaged DNA. Here we characterized the interactome of Mms22 and found that the Rtt101Mms22 ligase associates with the replisome progression complex during S-phase via the amino-terminal WD40 domain of Ctf4. Moreover, genetic screening for suppressors of the genotoxic sensitivity of rtt101Δ cells identified a cluster of replication proteins, among them a component of the fork protection complex, Mrc1. In contrast to rtt101Δ and mms22Δ cells, mrc1Δ rtt101Δ and mrc1Δ mms22Δ double mutants complete DNA replication upon replication stress by facilitating the repair/restart of stalled replication forks using a Rad52-dependent mechanism. Our results suggest that the Rtt101Mms22 E3 ligase does not induce Mrc1 degradation, but specifically counteracts Mrc1’s replicative function, possibly by modulating its interaction with the CMG (Cdc45-MCM-GINS) complex at stalled forks. PMID:26849847

  20. Silica Nanoparticles Induce Oxidative Stress and Autophagy but Not Apoptosis in the MRC-5 Cell Line

    PubMed Central

    Petrache Voicu, Sorina Nicoleta; Dinu, Diana; Sima, Cornelia; Hermenean, Anca; Ardelean, Aurel; Codrici, Elena; Stan, Miruna Silvia; Zărnescu, Otilia; Dinischiotu, Anca

    2015-01-01

    This study evaluated the in vitro effects of 62.5 µg/mL silica nanoparticles (SiO2 NPs) on MRC-5 human lung fibroblast cells for 24, 48 and 72 h. The nanoparticles’ morphology, composition, and structure were investigated using high resolution transmission electron microscopy, selected area electron diffraction and X-ray diffraction. Our study showed a decreased cell viability and the induction of cellular oxidative stress as evidenced by an increased level of reactive oxygen species (ROS), carbonyl groups, and advanced oxidation protein products after 24, 48, and 72 h, as well as a decreased concentration of glutathione (GSH) and protein sulfhydryl groups. The protein expression of Hsp27, Hsp60, and Hsp90 decreased at all time intervals, while the level of protein Hsp70 remained unchanged during the exposure. Similarly, the expression of p53, MDM2 and Bcl-2 was significantly decreased for all time intervals, while the expression of Bax, a marker for apoptosis, was insignificantly downregulated. These results correlated with the increase of pro-caspase 3 expression. The role of autophagy in cellular response to SiO2 NPs was demonstrated by a fluorescence-labeled method and by an increased level of LC3-II/LC3-I ratio. Taken together, our data suggested that SiO2 NPs induced ROS-mediated autophagy in MRC-5 cells as a possible mechanism of cell survival. PMID:26690408

  1. NASA'S SERVIR Gulf of Mexico Project: The Gulf of Mexico Regional Collaborative (GoMRC)

    NASA Technical Reports Server (NTRS)

    Quattrochi, Dale A.; Irwin, Daniel; Presson, Joan; Estes, Maury; Estes, Sue; Judd, Kathleen

    2006-01-01

    The Gulf of Mexico Regional Collaborative (GoMRC) is a NASA-funded project that has as its goal to develop an integrated, working, prototype IT infrastructure for Earth science data, knowledge and models for the five Gulf U.S. states and Mexico, and to demonstrate its ability to help decision-makers better understand critical Gulf-scale issues. Within this preview, the mission of this project is to provide cross cutting solution network and rapid prototyping capability for the Gulf of Mexico region, in order to demonstrate substantial, collaborative, multi-agency research and transitional capabilities using unique NASA data sets and models to address regional problems. SERVIR Mesoamerica is seen as an excellent existing framework that can be used to integrate observational and GIs data bases, provide a sensor web interface, visualization and interactive analysis tools, archival functions, data dissemination and product generation within a Rapid Prototyping concept to assist decision-makers in better understanding Gulf-scale environmental issues.

  2. Galactic interaction as the trigger for the young radio galaxy MRC B1221-423

    NASA Astrophysics Data System (ADS)

    Anderson, C. S.; Johnston, H. M.; Hunstead, R. W.

    2013-06-01

    Mergers between a massive galaxy and a small gas-rich companion (minor mergers) have been proposed as a viable mechanism for triggering radio emission in an active galaxy. Until now the problem has been catching this sequence of events as they occur. With MRC B1221-423, we have an active radio galaxy that has only recently been triggered, and a companion galaxy that provides the `smoking gun'. Using spectroscopic data taken with the VIsible Multi Object Spectrograph (VIMOS) integral field unit detector on the European Southern Observatory's Very Large Telescope, we have examined the distribution, ionization state and kinematics of ionized gas in this interacting system. We have also modelled the stellar continuum with synthesized spectra of stellar populations of different ages. From our study of the ionized gas, we have derived preliminary models for the geometry of the interaction, analysed the kinematic behaviour of the ionized gas, and examined the ionization mechanisms at work throughout the system. Our modelling of the stellar continuum allowed us to identify and date distinct stellar populations within the galaxy pair. We find evidence of multiple episodes of widespread starburst activity, and by dating these populations, we provide tentative insight into the history of the interaction.

  3. Production of [14C]fumonisin B1 by Fusarium moniliforme MRC 826 in corn cultures.

    PubMed Central

    Alberts, J F; Gelderblom, W C; Vleggaar, R; Marasas, W F; Rheeder, J P

    1993-01-01

    Kinetics of growth and fumonisin production by Fusarium moniliforme MRC 826 in corn "patty" cultures were investigated, and a technique was developed for the production of [14C]fumonisin B1 ([14C]FB1) by using L-[methyl-14C]methionine as the precursor. A significant (P < 0.01) correlation exists between fungal growth and FB1 (r = 0.89) and FB2 (r = 0.87) production in corn patties, beginning after 2 days and reaching the stationary phase after 14 days of incubation. [14C]FB1 was produced by adding L-[methyl-14C]methionine daily to cultures during the logarithmic phase of production. Incorporation of the isotope occurred at C-21 and C-22 of the fumonism molecule and was enhanced in the presence of unlabeled L-methionine. Although the concentration of exogenous unlabeled methionine is critical for incorporation of the 14C label, optimum incorporation was achieved by adding 50 mg of unlabeled L-methionine and 200 mu Ci of L-[methyl-14C]methionine to a corn patty (30 g) over a period of 9 days, yielding [14C]FB1 with a specific activity of 36 mu Ci/mmol. PMID:8368853

  4. MRC OX-2 antigen: a lymphoid/neuronal membrane glycoprotein with a structure like a single immunoglobulin light chain.

    PubMed Central

    Clark, M J; Gagnon, J; Williams, A F; Barclay, A N

    1985-01-01

    The MRC OX-2 antigen is a rat cell surface glycoprotein of mol. wt. 41 000-47 000 found on neurones, thymocytes, B cells, follicular dendritic cells and endothelium. We now report the amino sequence for this antigen as deduced from the nucleotide sequence of cDNA clones detected by use of an oligonucleotide probe. The sequence contains 248 amino acid residues of which 202 residues are likely to be outside the cell with two domains that show homology with immunoglobulins. The N-terminal domain fits best with Ig V domains and Thy-1 antigen while the C-terminal part is like an Ig C domain. Thus the structure overall is similar to an Ig light chain or the T cell receptor beta chain. Three glycosylation sites are identified on each of the MRC OX-2 antigen domains. Images Fig. 1. Fig. 2. PMID:2862025

  5. MOLECULAR CO(1-0) GAS IN THE z {approx} 2 RADIO GALAXY MRC 0152-209

    SciTech Connect

    Emonts, B. H. C.; Feain, I.; Mao, M. Y.; Norris, R. P.; Ekers, R. D.; Rees, G.; Stevens, J. B.; Miley, G.; Roettgering, H. J. A.; Villar-Martin, M.; Sadler, E. M.; Morganti, R.; Oosterloo, T. A.; Saikia, D. J.; Tadhunter, C. N.

    2011-06-10

    We report the detection of molecular CO(1-0) gas in the high-z radio galaxy MRC 0152-209 (z = 1.92) with the Australia Telescope Compact Array Broadband Backend (ATCA/CABB). This is the third known detection of CO(1-0) in a high-z radio galaxy to date. CO(1-0) is the most robust tracer of the overall molecular gas content (including the widespread, low-density, and sub-thermally excited component), hence observations of CO(1-0) are crucial for studying galaxy evolution in the early universe. We derive L'{sub CO} = 6.6 {+-} 2.0 x 10{sup 10} K km s{sup -1} pc{sup 2} for MRC 0152-209, which is comparable to that derived from CO(1-0) observations of several high-z submillimeter and star-forming BzK galaxies. The CO(1-0) traces a total molecular hydrogen mass of M{sub H{sub 2}} = 5 x 10{sup 10} ({alpha}{sub x}/0.8) M{sub sun}. MRC 0152-209 is an infrared bright radio galaxy, in which a large reservoir of cold molecular gas has not (yet) been depleted by star formation or radio source feedback. Its compact radio source is reliably detected at 40 GHz and has a steep spectral index of {alpha} = -1.3 between 1.4 and 40 GHz (4-115 GHz in the galaxy's rest frame). MRC 0152-209 is part of an ongoing systematic ATCA/CABB survey of CO(1-0) in high-z radio galaxies between 1.7 < z < 3.

  6. Properties of Lya Emitters Around the Radio Galaxy MRC 0316-257

    SciTech Connect

    Venemans, B; Rottgering, H; Miley, G; Kurk, J; De Breuck, C; van Breugel, W; Carilli, C; Ford, H; Heckman, T; Pentericci, L; McCarthy, P

    2004-08-12

    Observations of the radio galaxy MRC 0316-257 at z = 3.13 and the surrounding field are presented. Using narrow- and broad-band imaging obtained with the VLT*, 92 candidate Ly{alpha} emitters with a rest-frame equivalent width of > 15 AngstromS were selected in a {approx} 7{prime} x 7{prime} field around the radio galaxy. Spectroscopy of 40 candidate emitters resulted in the discovery of 33 emission line galaxies of which 31 are Ly{alpha} emitters with redshifts similar to that of the radio galaxy, while the remaining two galaxies turned out to be [{omicron} II] emitters. The Ly{alpha} profiles had widths (FWHM) corresponding to 120-800 kms{sup -1},with a median of 260 kms{sup -1}. Where the signal-to-noise spectra was large enough, the Ly{alpha} profiles are found to be asymmetric, with apparent absorption troughs blueward of the profile peaks, indicative of absorption along the line of sight of an {Eta}{Iota} mass of 1-5000 {mu}{circle_dot}. Besides that of the radio galaxy and one of the emitters that is an QSO, the continuum of the emitters is faint, with luminosities ranging from 1.3 L{sub *} to < 0.03 L{sub *}.The colors of the confirmed emitters are, on average, very blue. The median UV continuum slope is {beta}=-1.65, bluer than the average slope of LBGs with Ly{alpha} emitters is 2.6 {Mu}{circle_dot}{sup -1} as measured by the Ly{alpha} emission line or < 3.9 {Mu}{circle_dot}{sup -1} as measured by the UV continuum. The properties of the Ly{alpha} galaxies (faint, blue and small) are consistent with young star forming galaxies which are nearly dust free. The density of Ly{alpha} emitting galaxies in the field around MRC 0316-257 is a factor of 3.3{sup +0.5}{sub -0.4} larger compared with the density of Ly{alpha} emitters at that redshift. The velocity distribution of the spectroscopically confirmed emitters has a dispersion of 640 km s{sup -1}, corresponding to a FWHM of 1510 km s{sup -1}, which is substantially smaller than the width of the narrow

  7. Toxicity of culture material of Fusarium verticillioides strain MRC 826 to nonhuman primates.

    PubMed Central

    Gelderblom, W C; Seier, J V; Snijman, P W; Van Schalkwyk, D J; Shephard, G S; Marasas, W F

    2001-01-01

    We conducted a chronic feeding study in vervet monkeys (Cercopithecus aethiops) over 13.5 years. The experimental design consisted of two dietary treatment groups, each including males and females, fed varying levels of culture material of Fusarium verticillioides (Sacc.) Nirenberg (= F. moniliforme Sheldon) strain MRC 826 mixed into their daily food ration. Two females were included as treatment controls. We conducted blood chemical analyses bimonthly and recorded all clinical signs during the course of the experiment. We took liver biopsies at various stages during the initial phase of the experiment. Several monkeys were terminated in extremis during the experiment. Detailed feed intake profiles were determined 5 years after the experiment began, and the fumonisin B (FB) mycotoxin content of the feed was determined during the final stages of the experiment. The apparent FB consumption patterns were related to changes observed in the biochemical parameters in the blood and urine, including the liver function enzymes and creatinine clearance as well as differential blood counts and sphingolipid levels in the serum and urine. An apparent no-effect threshold for kidney and liver damage is estimated to be between 0.11 and 0.18 mg FB/kg body weight (bw)/day, which corresponds to a feed contamination level of between 8.21 and 13.25 mg FB/kg bw diet. Apart from the effects on the liver and kidney, a wide variety of parameters, including cholesterol and creatine kinase, were also adversely affected. Several blood parameters, including white and red blood cells, also significantly decreased in the treated animals. The serum sphinganine level and the sphingosine/sphinganine ratio, monitored toward the end of the experiment, significantly increased in both the low-dose and high-dose animals. The present study provides important information about the diversity of lesions induced by culture material of F. verticillioides in vervet monkeys and the dosage levels of fumonisins

  8. Age, Neurological Status MRC Scale, and Postoperative Morbidity are Prognostic Factors in Patients with Glioblastoma Treated by Chemoradiotherapy

    PubMed Central

    Verlut, Clotilde; Mouillet, Guillaume; Magnin, Eloi; Buffet-Miny, Joëlle; Viennet, Gabriel; Cattin, Françoise; Billon-Grand, Nora Clelia; Bonnet, Emilie; Servagi-Vernat, Stéphanie; Godard, Joël; Billon-Grand, Romain; Petit, Antoine; Moulin, Thierry; Cals, Laurent; Pivot, Xavier; Curtit, Elsa

    2016-01-01

    INTRODUCTION Temozolomide and concomitant radiotherapy followed by temozolomide has been used as a standard therapy for the treatment of newly diagnosed glioblastoma multiform since 2005. A search for prognostic factors was conducted in patients with glioblastoma routinely treated by this strategy in our institution. METHODS This retrospective study included all patients with histologically proven glioblastoma diagnosed between June 1, 2005, and January 1, 2012, in the Franche-Comté region and treated by radiotherapy (daily fractions of 2 Gy for a total of 60 Gy) combined with temozolomide at a dose of 75 mg/m2 per day, followed by six cycles of maintenance temozolomide (150–200 mg/m2, five consecutive days per month). The primary aim was to identify prognostic factors associated with overall survival (OS) in this cohort of patients. RESULTS One hundred three patients were included in this study. The median age was 64 years. The median OS was 13.7 months (95% confidence interval, 12.5–15.9 months). In multivariate analysis, age over 65 years (hazard ratio [HR] = 1.88; P = 0.01), Medical Research Council (MRC) scale 3–4 (HR = 1.62; P = 0.038), and occurrence of postoperative complications (HR = 2.15; P = 0.028) were associated with unfavorable OS. CONCLUSIONS This study identified three prognostic factors in patients with glioblastoma eligible to the standard chemotherapy and radiotherapy treatment. Age over 65 years, MRC scale 3–4, and occurrence of postoperative complications were associated with unfavorable OS. A simple clinical evaluation including these three factors enables to estimate the patient prognosis. MRC neurological scale could be a useful, quick, and simple measure to assess neurological status in glioblastoma patients. PMID:27559302

  9. Neoplastic transformation of human lung fibroblast MRC-5 SV2 cells induced by benzo[a]pyrene and confluence culture.

    PubMed

    Zhu, Huijun; Gooderham, Nigel

    2002-08-15

    Benzo[a]pyrene (BaP) is potent rodent carcinogen and a reputed human carcinogen. Although much is known about its metabolic activation leading to DNA damage, the mechanisms of its actions are not as well understood at a cellular level. In addressing this, we have established an in vitro model that follows the progression toward neoplastic transformation induced by BaP. The model uses immortal nontumorigenic human lung fibroblast MRC-5 SV2 cells as effectors, cocultured with a metabolically competent human lymphoblastoid line h1A1v2 (activator cells). Treatment of the coculture with BaP for 48 h induced a dose-dependent decrease in cloning efficiency of the MRC-5 SV2 cells; nevertheless, cultures continued to progress to confluence. At prolonged confluence culture (day 11), an elevation in the proportion of G2-M phase cells was detected by flow cytometry. By day 15, the G2-M phase peak disappeared, accordant with the appearance of a population with DNA content greater than the cells in G2-M phase. These changes in DNA ploidy were coincident with changes in morphology, specifically the appearance of enlarged and irregular-shaped nuclei. Confluence culture of BaP-treated MRC-5 SV2 cells for more than 2 weeks resulted in cell death; however, a few colonies survived the crisis to reach confluence again after an additional 10-14 days. The number of death-resistant colonies was proportional to the dose of BaP, with the majority of the cells exhibiting abnormal morphology. The degree of morphological change progressively increased with successive rounds of confluence. Cells that survived three rounds of confluence adopted a vastly different morphology, becoming polygonal, spindle, or other irregular-shaped, and acquired the ability to form large dense clumps that grew in an anchorage-independent manner. In parallel experiments, treatment with the vehicle alone (DMSO) resulted in substantially less death resistance and lower numbers of high-density clumps. Our studies

  10. Development of a lifestyle intervention using the MRC framework for diabetes prevention in people with impaired glucose regulation

    PubMed Central

    Troughton, Jacqui; Chatterjee, Sudesna; Hill, Siân E.; Daly, Heather; Martin Stacey, Lorraine; Stone, Margaret A.; Patel, Naina; Khunti, Kamlesh; Yates, Thomas; Gray, Laura J.; Davies, Melanie J.

    2016-01-01

    Background We report development of a group-based lifestyle intervention, Let's Prevent, using the UK Medical Research Council (MRC) framework, and delivered by structured education to prevent type 2 diabetes mellitus (T2DM) in people with impaired glucose regulation (IGR) in a UK multi-ethnic population. Methods Diabetes Education and Self-Management for Ongoing and Newly Diagnosed (DESMOND) is the first national T2DM programme that meets National Institute for Health and Care Excellence criteria and formed the basis for Let's Prevent. An iterative cycle of initial development, piloting, collecting and collating qualitative and quantitative data, and reflection and modification, was used to inform and refine lifestyle intervention until it was fit for evaluation in a definitive randomized controlled trial (RCT). The programme encouraged IGR self-management using simple, non-technical language and visual aids. Results Qualitative and quantitative data suggested that intervention resulted in beneficial short-term behaviour change such as healthier eating patterns, improved health beliefs and greater participant motivation and empowerment. We also demonstrated that recruitment strategy and data collection methods were feasible for RCT implementation. Conclusions Let's Prevent was developed following successful application of MRC framework criteria and the subsequent RCT will determine whether it is feasible, reliable and transferable from research into a real-world NHS primary healthcare setting. Trial Registration ISRCTN80605705. PMID:26311822

  11. SER Performance of Enhanced Spatial Multiplexing Codes with ZF/MRC Receiver in Time-Varying Rayleigh Fading Channels

    PubMed Central

    Lee, In-Ho

    2014-01-01

    We propose enhanced spatial multiplexing codes (E-SMCs) to enable various encoding rates. The symbol error rate (SER) performance of the E-SMC is investigated when zero-forcing (ZF) and maximal-ratio combining (MRC) techniques are used at a receiver. The proposed E-SMC allows a transmitted symbol to be repeated over time to achieve further diversity gain at the cost of the encoding rate. With the spatial correlation between transmit antennas, SER equations for M-ary QAM and PSK constellations are derived by using a moment generating function (MGF) approximation of a signal-to-noise ratio (SNR), based on the assumption of independent zero-forced SNRs. Analytic and simulated results are compared for time-varying and spatially correlated Rayleigh fading channels that are modelled as first-order Markovian channels. Furthermore, we can find an optimal block length for the E-SMC that meets a required SER. PMID:25114969

  12. Comparison of protein expression pattern between the Plasmodium falciparum chloroquine-resistant RKL9 and chloroquine-sensitive MRC2 strains

    PubMed Central

    Antony, Hiasindh Ashmi; Pathak, Vrushali; Ghosh, Kanjaksha; Parija, Subhash Chandra

    2016-01-01

    Objective: The objective of this study was to compare the protein expression patterns of Plasmodium falciparum extracellular and intracellular proteins separated by two-dimensional electrophoresis (2-DE) from the chloroquine-sensitive (CQS) MRC2 strain and chloroquine-resistant (CQR) RKL9 strain. Materials and Methods: Both the extracellular protein (ECP) and intracellular protein (ICP) were extracted and solubilized. The proteins were separated by 2-DE, first based on their charges using isoelectric focusing and then their sizes by electrophoresis. The separated protein spots were detected by silver staining, and further, the protein spot density was analyzed by an image analysis software. Results: 2-DE separated the proteins extracted from the CQS and CQR strains based on their differentially expressed protein patterns. Extracellular Protein Analysis: A total of 109 and 77 protein spots were detected by image analysis of ECP extracted from MRC2 and RKL9 strains, respectively. There was a marked reduction in protein expression pattern in the CQR strain when compared with the CQS strain. Interestingly, 50 and 18 protein spots were uniquely expressed in MRC2 and RKL9 strains, respectively. When MRC2 strain-expressed proteins were taken as the control, 12 upregulated and 14 downregulated protein spots were observed in the RKL9 strain-extracted proteins. Intracellular Protein Analysis: ICP extracted from MRC2 and RKL9 strains showed 187 and 199 protein spots by an image analysis software, and a small enhancement of protein expression was measured when comparing the CQR strain with CQS strain. There were 67 and 79 unique protein spots detected in MRC2 and RKL9 strains, respectively. A total of 120 protein spots were similar when MRC2 proteins were taken as the control; among these protein spots, 40 upregulated and 22 downregulated protein spots were detected in RKL9 strain-expressed protein. Conclusions: Both these unique and matched protein spots might be molecularly

  13. Serendipitous detection of an overdensity of Herschel-SPIRE 250 μm sources south of MRC 1138-26

    NASA Astrophysics Data System (ADS)

    Valtchanov, Ivan; Altieri, B.; Berta, S.; Chapin, E.; Coia, D.; Conversi, L.; Dannerbauer, H.; Domínguez-Sánchez, H.; Rawle, T. D.; Sánchez-Portal, M.; Santos, J. S.; Temporin, S.

    2013-12-01

    We report the serendipitous detection of a significant overdensity of Herschel-Spectral and Photometric Imaging Receiver 250 μm sources in the vicinity of MRC 1138-26. We use an adaptive kernel density estimate to quantify the significance, including a comparison with other fields. The overdensity has a size of ˜3.5-4 arcmin and stands out at ˜5σ with respect to the background estimate. No features with similar significance were found in four Herschel-observed extragalactic control fields: GOODS-North, Lockman, COSMOS and UDS. The chance of having a similar overdensity in a field with the same number but randomly distributed sources is less than 2 per cent. The clump is also visible as a low-surface-brightness feature in the Planck 857 GHz map. We detect 76 sources at 250 μm (with a signal-to-noise ratio greater than 3), in a region of 4 arcmin radius (or 1.51 ± 0.17 arcmin-2); 43 of those (or 0.86 ± 0.13 arcmin-2) are above a flux density limit of 20 mJy. This is a factor of 3.6 in excess over the average 0.24 ± 0.02 arcmin-2 in the four control fields, considering only the sources above 20 mJy. We also find an excess in the number counts of sources with 250 μm flux densities between 30 and 40 mJy, compared to deep extragalactic blank-field number counts. Assuming a fixed dust temperature (30 K) and emissivity (β = 1.5), a crude, blackbody-derived redshift distribution, zBB, of the detected sources is significantly different from the distributions in the control fields and exhibits a significant peak at zBB ≈ 1.5, although the actual peak redshift is highly degenerate with the temperature. We tentatively suggest, based on zBB and the similar S250/S350 colours of the sources within the peak, that a significant fraction of the sources in the clump may be at a similar redshift. Since the overdensity lies ˜ 7 arcmin south of the z = 2.16 Spiderweb protocluster MRC 1138-26, an intriguing possibility (that is presently unverifiable given the data in hand

  14. Cytotoxic and genotoxic effects of high concentrations of the immunosuppressive drugs cyclosporine and tacrolimus in MRC-5 cells.

    PubMed

    Cilião, H L; Ribeiro, D L; Camargo-Godoy, R B O; Specian, A F L; Serpeloni, J M; Cólus, I M S

    2015-02-01

    Immunosuppressive drugs are used to suppress immune system activity in transplant patients and reduce the risk of organ rejection. The present study evaluated the potential cytotoxic, genotoxic and mutagenic of the immunosuppressive drugs cyclosporine (CsA) and tacrolimus (FK-506) on normal human fibroblasts (MRC-5 cells). Based on plasma concentrations of the immunosuppressive drugs, which were obtained from the records of kidney transplant patients at the Kidney Institute of Londrina, Brazil, 11 concentrations of each immunosuppressive were chosen to evaluate cell viability using the MTT assay. From these results, CsA and FK-506 concentrations of 135, 300, 675, and 1520 ng/ml and 8, 16, 24, and 32 ng/ml, respectively, were evaluated using (i) the comet assay, (ii) the nuclear division index (NDI), (iii) the micronucleus test (CBMN) and (iv) cell proliferation curves generated by quantifying cell numbers and protein levels. In this study, 1520 to 3420 ng/ml CsA decreased cell viability after 48 h of exposure. Genotoxic effects were observed only with a concentration of 1520 ng/ml after 3h of exposure and with concentrations of 675 and 1520 ng/ml after 24h of exposure. Mutagenic effects were observed only for the concentration of 1520 ng/ml. FK-506 decreased cell viability after 72 h of exposure for concentrations up to 20 ng/ml; genotoxic effects were observed with concentrations up to 8 ng/ml for both treatment times (3 and 24h) and mutagenic effects were observed with concentrations of 24 and 32 ng/ml after 24h of treatment. The cell proliferation curves demonstrated the absence of cytostatic effects of these drugs, and these data were confirmed by the NDI analysis. Our results suggest that concentrations lower than 300 ng/ml of CsA and 16 ng/ml of FK-506 are safe for use, as they did not induce genotoxic and mutagenic damage or affect MRC-5 cell viability and proliferation.

  15. Discovery of an Obscured Broad-Line Region in the High-Redshift Radio Galaxy MRC 2025-218.

    PubMed

    Larkin; McLean; Graham; Becklin; Figer; Gilbert; Levenson; Teplitz; Wilcox; Glassman

    2000-04-10

    This Letter presents infrared spectra taken with the newly commissioned near-infrared spectrometer (NIRSPEC) on the Keck II telescope of the high-redshift radio galaxy MRC 2025-218 (z=2.63). These observations represent the deepest infrared spectra of a radio galaxy to date and have allowed for the detection of Hbeta, [O iii] lambdalambda4959, 5007, [O i] lambda6300, Halpha, [N ii] lambdalambda6548, 6583, and [S ii] lambdalambda6716, 6713. The Halpha emission is very broad (FWHM=9300 km s-1) and luminous (2.6x1044 ergs s-1), and it is very comparable to the line widths and strengths of radio-loud quasars at the same redshift. This strongly supports active galactic nucleus unification models linking radio galaxies and quasars, although we discuss some of the outstanding differences. The line [O iii] lambda5007 is extremely strong and has extended emission with large relative velocities toward the nucleus. We also derive that if the extended emission is due to star formation, each knot has a star formation rate comparable to a Lyman-break galaxy at the same redshift.

  16. Dosimetry comparison and characterisation of an Al K ultrasoft x-ray beam from an MRC cold-cathode source.

    PubMed

    Hoshi, M; Goodhead, D T; Brenner, D J; Bance, D A; Chmielewski, J J; Paciotti, M A; Bradbury, J N

    1985-10-01

    Ultrasoft x-rays of 0.3-5 keV have provided a unique tool for the investigation of intracellular mechanisms of radiation action in biological organisms, including mammalian cells. However, their use presents unique practical problems in dosimetry and experimental design. Detailed interpretation of the biological results requires reliable dosimetry and well characterised monoenergetic beams. This paper presents a comparison between two fundamentally different dosimetric techniques, namely the ionisation current in an extrapolation chamber and photon counts in a proportional counter. Agreement within 7% was obtained when these two methods were applied to an Al K x-ray beam (1.5 keV) from an MRC cold-cathode transmission target discharge tube as previously used in many biological experiments. Photographic film was calibrated as a relative dosimetric technique and used for investigation of the intensity uniformity of the radiation field. These techniques provide a comprehensive characterisation of the beam in the position of the biological cells, including photon flux (or absorbed dose rate), spectral purity (showing much less than 1% bremsstrahlung relative to characteristic Al x-rays) and uniformity over the irradiation area (within about 5% for mammalian cell irradiations).

  17. VizieR Online Data Catalog: Redshifts in the surroundings of MRC 0156-252 (Galametz+, 2013)

    NASA Astrophysics Data System (ADS)

    Galametz, A.; Stern, D.; Pentericci, L.; De Breuck, C.; Vernet, J.; Wylezalek, D.; Fassbender, R.; Hatch, N.; Kurk, J.; Overzier, R.; Rettura, A.; Seymour, N.

    2014-03-01

    We made use of the VLT/FORS2 multi-object spectrograph to target a galaxy structure candidate in the surroundings of the radio galaxy MRC0156-252 at z=2.02, reported in Galametz et al. (2010A&A...522A..58G). We targeted ~80 high-redshift galaxy candidates. The two slit masks were observed on UT 2012 October 20 using the MXU mode of FORS2 with the blue-optimized detector and the 300V+10 grism with no order-sorting filter to cover a typical wavelength range of 3300-6600Å (1100-2200Å at z=2). We obtained robust spectroscopic redshifts for 45 targets between 0.2

  18. Extreme Gas Kinematics in the z=2.2 Powerful Radio Galaxy MRC1138-262: Evidence for Efficient AGN Feedback in the Early Universe?

    SciTech Connect

    Nesvadba, N H; Lehnert, M D; Eisenhauer, F; Gilbert, A M; Tecza, M; Abuter, R

    2007-06-26

    To explain the properties of the most massive low-redshift galaxies and the shape of their mass function, recent models of galaxy evolution include strong AGN feedback to complement starburst-driven feedback in massive galaxies. Using the near-infrared integral-field spectrograph SPIFFI on the VLT, we searched for direct evidence for such a feedback in the optical emission line gas around the z = 2.16 powerful radio galaxy MRC1138-262, likely a massive galaxy in formation. The kpc-scale kinematics, with FWHMs and relative velocities {approx}< 2400 km s{sup -1} and nearly spherical spatial distribution, do not resemble large-scale gravitational motion or starburst-driven winds. Order-of-magnitude timescale and energy arguments favor the AGN as the only plausible candidate to accelerate the gas, with a total energy injection of {approx} few x 10{sup 60} ergs or more, necessary to power the outflow, and relatively efficient coupling between radio jet and ISM. Observed outflow properties are in gross agreement with the models, and suggest that AGN winds might have a similar, or perhaps larger, cosmological significance than starburst-driven winds, if MRC1138-262 is indeed archetypal. Moreover, the outflow has the potential to remove significant gas fractions ({approx}< 50%) from a > L* galaxy within a few 10 to 100 Myrs, fast enough to preserve the observed [{alpha}/Fe] overabundance in massive galaxies at low redshift. Using simple arguments, it appears that feedback like that observed in MRC1138-262 may have sufficient energy to inhibit material from infalling into the dark matter halo and thus regulate galaxy growth as required in some recent models of hierarchical structure formation.

  19. Average bit error rate performance analysis of subcarrier intensity modulated MRC and EGC FSO systems with dual branches over M distribution turbulence channels

    NASA Astrophysics Data System (ADS)

    Wang, Ran-ran; Wang, Ping; Cao, Tian; Guo, Li-xin; Yang, Yintang

    2015-07-01

    Based on the space diversity reception, the binary phase-shift keying (BPSK) modulated free space optical (FSO) system over Málaga (M) fading channels is investigated in detail. Under independently and identically distributed and independently and non-identically distributed dual branches, the analytical average bit error rate (ABER) expressions in terms of H-Fox function for maximal ratio combining (MRC) and equal gain combining (EGC) diversity techniques are derived, respectively, by transforming the modified Bessel function of the second kind into the integral form of Meijer G-function. Monte Carlo (MC) simulation is also provided to verify the accuracy of the presented models.

  20. Balancing Selection of a Frame-Shift Mutation in the MRC2 Gene Accounts for the Outbreak of the Crooked Tail Syndrome in Belgian Blue Cattle

    PubMed Central

    Li, Wanbo; Dive, Marc; Tamma, Nico; Michaux, Charles; Druet, Tom; Huijbers, Ivo J.; Isacke, Clare M.; Coppieters, Wouter; Georges, Michel; Charlier, Carole

    2009-01-01

    We herein describe the positional identification of a 2-bp deletion in the open reading frame of the MRC2 receptor causing the recessive Crooked Tail Syndrome in cattle. The resulting frame-shift reveals a premature stop codon that causes nonsense-mediated decay of the mutant messenger RNA, and the virtual absence of functional Endo180 protein in affected animals. Cases exhibit skeletal anomalies thought to result from impaired extracellular matrix remodeling during ossification, and as of yet unexplained muscular symptoms. We demonstrate that carrier status is very significantly associated with desired characteristics in the general population, including enhanced muscular development, and that the resulting heterozygote advantage caused a selective sweep which explains the unexpectedly high frequency (25%) of carriers in the Belgian Blue Cattle Breed. PMID:19779552

  1. Using dose-surface maps to predict radiation-induced rectal bleeding: a neural network approach.

    PubMed

    Buettner, Florian; Gulliford, Sarah L; Webb, Steve; Partridge, Mike

    2009-09-01

    The incidence of late-toxicities after radiotherapy can be modelled based on the dose delivered to the organ under consideration. Most predictive models reduce the dose distribution to a set of dose-volume parameters and do not take the spatial distribution of the dose into account. The aim of this study was to develop a classifier predicting radiation-induced rectal bleeding using all available information on the dose to the rectal wall. The dose was projected on a two-dimensional dose-surface map (DSM) by virtual rectum-unfolding. These DSMs were used as inputs for a classification method based on locally connected neural networks. In contrast to fully connected conventional neural nets, locally connected nets take the topology of the input into account. In order to train the nets, data from 329 patients from the RT01 trial (ISRCTN 47772397) were split into ten roughly equal parts. By using nine of these parts as a training set and the remaining part as an independent test set, a ten-fold cross-validation was performed. Ensemble learning was used and 250 nets were built from randomly selected patients from the training set. Out of these 250 nets, an ensemble of expert nets was chosen. The performances of the full ensemble and of the expert ensemble were quantified by using receiver-operator-characteristic (ROC) curves. In order to quantify the predictive power of the shape, ensembles of fully connected conventional neural nets based on dose-surface histograms (DSHs) were generated and their performances were quantified. The expert ensembles performed better than or equally as well as the full ensembles. The area under the ROC curve for the DSM-based expert ensemble was 0.64. The area under the ROC curve for the DSH-based expert ensemble equalled 0.59. This difference in performance indicates that not only volumetric, but also morphological aspects of the dose distribution are correlated to rectal bleeding after radiotherapy. Thus, the shape of the dose

  2. Using dose-surface maps to predict radiation-induced rectal bleeding: a neural network approach

    NASA Astrophysics Data System (ADS)

    Buettner, Florian; Gulliford, Sarah L.; Webb, Steve; Partridge, Mike

    2009-09-01

    The incidence of late-toxicities after radiotherapy can be modelled based on the dose delivered to the organ under consideration. Most predictive models reduce the dose distribution to a set of dose-volume parameters and do not take the spatial distribution of the dose into account. The aim of this study was to develop a classifier predicting radiation-induced rectal bleeding using all available information on the dose to the rectal wall. The dose was projected on a two-dimensional dose-surface map (DSM) by virtual rectum-unfolding. These DSMs were used as inputs for a classification method based on locally connected neural networks. In contrast to fully connected conventional neural nets, locally connected nets take the topology of the input into account. In order to train the nets, data from 329 patients from the RT01 trial (ISRCTN 47772397) were split into ten roughly equal parts. By using nine of these parts as a training set and the remaining part as an independent test set, a ten-fold cross-validation was performed. Ensemble learning was used and 250 nets were built from randomly selected patients from the training set. Out of these 250 nets, an ensemble of expert nets was chosen. The performances of the full ensemble and of the expert ensemble were quantified by using receiver-operator-characteristic (ROC) curves. In order to quantify the predictive power of the shape, ensembles of fully connected conventional neural nets based on dose-surface histograms (DSHs) were generated and their performances were quantified. The expert ensembles performed better than or equally as well as the full ensembles. The area under the ROC curve for the DSM-based expert ensemble was 0.64. The area under the ROC curve for the DSH-based expert ensemble equalled 0.59. This difference in performance indicates that not only volumetric, but also morphological aspects of the dose distribution are correlated to rectal bleeding after radiotherapy. Thus, the shape of the dose

  3. School characteristics and adolescent smoking. Results from the MRC/Derbyshire Smoking Study 1974-8 and from a follow up in 1981.

    PubMed

    Murray, M; Kiryluk, S; Swan, A V

    1984-06-01

    In the MRC/Derbyshire Smoking Study a cohort of about 6000 adolescents was surveyed annually from 1974 when they entered secondary school aged 11-12 years until 1978 when they reached 15-16 years. In 1981 after the adolescents had left school they were again surveyed by post. Each year from 1974 to 1978 and again in 1981 they answered a questionnaire on their smoking behaviour and other issues. Information on the schools attended by these adolescents was obtained from their teachers and headteachers. This paper examines the relation between the school environment and the adolescents' smoking behaviour both before and after leaving school. The prevalence of smoking was higher among those boys who attended schools that were single sex, non-denominational, or had a parent-teacher association, no health education, no female teachers, or whose headteacher smoked cigarettes. Among girls the prevalence of smoking was higher if they attended a school that had optional school uniform and no health or antismoking education. The importance of these findings for the development of effective preventive measures is discussed. PMID:6747518

  4. Lack of effects on key cellular parameters of MRC-5 human lung fibroblasts exposed to 370 mT static magnetic field.

    PubMed

    Romeo, Stefania; Sannino, Anna; Scarfì, Maria Rosaria; Massa, Rita; d'Angelo, Raffaele; Zeni, Olga

    2016-01-01

    The last decades have seen increased interest toward possible adverse effects arising from exposure to intense static magnetic fields. This concern is mainly due to the wider and wider applications of such fields in industry and clinical practice; among them, Magnetic Resonance Imaging (MRI) facilities are the main sources of exposure to static magnetic fields for both general public (patients) and workers. In recent investigations, exposures to static magnetic fields have been demonstrated to elicit, in different cell models, both permanent and transient modifications in cellular endpoints critical for the carcinogenesis process. The World Health Organization has therefore recommended in vitro investigations as important research need, to be carried out under strictly controlled exposure conditions. Here we report on the absence of effects on cell viability, reactive oxygen species levels and DNA integrity in MRC-5 human foetal lung fibroblasts exposed to 370 mT magnetic induction level, under different exposure regimens. Exposures have been performed by using an experimental apparatus designed and realized for operating with the static magnetic field generated by permanent magnets, and confined in a magnetic circuit, to allow cell cultures exposure in absence of confounding factors like heating or electric field components. PMID:26762783

  5. Lack of effects on key cellular parameters of MRC-5 human lung fibroblasts exposed to 370 mT static magnetic field

    PubMed Central

    Romeo, Stefania; Sannino, Anna; Scarfì, Maria Rosaria; Massa, Rita; d’Angelo, Raffaele; Zeni, Olga

    2016-01-01

    The last decades have seen increased interest toward possible adverse effects arising from exposure to intense static magnetic fields. This concern is mainly due to the wider and wider applications of such fields in industry and clinical practice; among them, Magnetic Resonance Imaging (MRI) facilities are the main sources of exposure to static magnetic fields for both general public (patients) and workers. In recent investigations, exposures to static magnetic fields have been demonstrated to elicit, in different cell models, both permanent and transient modifications in cellular endpoints critical for the carcinogenesis process. The World Health Organization has therefore recommended in vitro investigations as important research need, to be carried out under strictly controlled exposure conditions. Here we report on the absence of effects on cell viability, reactive oxygen species levels and DNA integrity in MRC-5 human foetal lung fibroblasts exposed to 370 mT magnetic induction level, under different exposure regimens. Exposures have been performed by using an experimental apparatus designed and realized for operating with the static magnetic field generated by permanent magnets, and confined in a magnetic circuit, to allow cell cultures exposure in absence of confounding factors like heating or electric field components. PMID:26762783

  6. Impact of PTEN abnormalities on outcome in pediatric patients with T-cell acute lymphoblastic leukemia treated on the MRC UKALL2003 trial.

    PubMed

    Jenkinson, S; Kirkwood, A A; Goulden, N; Vora, A; Linch, D C; Gale, R E

    2016-01-01

    PTEN gene inactivation by mutation or deletion is common in pediatric T-cell acute lymphoblastic leukemia (T-ALL), but the impact on outcome is unclear, particularly in patients with NOTCH1/FBXW7 mutations. We screened samples from 145 patients treated on the MRC UKALL2003 trial for PTEN mutations using heteroduplex analysis and gene deletions using single nucleotide polymorphism arrays, and related genotype to response to therapy and long-term outcome. PTEN loss-of-function mutations/gene deletions were detected in 22% (PTEN(ABN)). Quantification of mutant level indicated that 67% of mutated cases harbored more than one mutant, with up to four mutants detected, consistent with the presence of multiple leukemic sub-clones. Overall, 41% of PTEN(ABN) cases were considered to have biallelic abnormalities (mutation and/or deletion) with complete loss of PTEN in a proportion of cells. In addition, 9% of cases had N- or K-RAS mutations. Neither PTEN nor RAS genotype significantly impacted on response to therapy or long-term outcome, irrespective of mutant level, and there was no evidence that they changed the highly favorable outcome of patients with double NOTCH1/FBXW7 mutations. These results indicate that, for pediatric patients treated according to current protocols, routine screening for PTEN or RAS abnormalities at diagnosis is not warranted to further refine risk stratification.

  7. Childhood Environment and Mental Wellbeing at Age 60-64 Years: Prospective Evidence from the MRC National Survey of Health and Development

    PubMed Central

    Stafford, Mai; Gale, Catharine R.; Mishra, Gita; Richards, Marcus; Black, Stephanie; Kuh, Diana L.

    2015-01-01

    Background Mental wellbeing, conceptualised as positive affect, life satisfaction and realisation of needs that contribute to psychological growth, captures more than the absence of mental ill health. Several nations now aim to monitor and improve mental wellbeing. Whilst many studies document associations between adverse childhood experiences and mental disorders in adulthood, possible links between childhood experiences and adult mental wellbeing have so far received less attention. Methods Using data from 1976 men and women in the MRC National Survey for Health and Development, we investigated prospective associations between childhood socioeconomic and psychosocial environments and the Warwick Edinburgh Mental Wellbeing Scale, designed to capture both hedonic and eudaimonic facets of wellbeing, at age 60-64. Results Whilst there was no evidence that childhood socioeconomic circumstances were related to later wellbeing independently of other childhood experiences, elements of childrearing and parenting, parental health and adjustment, and childhood illness were related. More advantaged socioeconomic position was associated with greater wellbeing but this did not explain the links between these childhood exposures and adult wellbeing, suggesting alternative explanatory pathways should be considered. Conclusions Childhood illness and family psychosocial environment are associated with mental wellbeing in early older age, with effects sizes that are larger or comparable to socioeconomic circumstances in adulthood. Initiatives to improve the nation’s mental wellbeing that include programmes targeted to supporting families and children may additionally have benefits that continue into older age. PMID:26030929

  8. The influence of non-DNA-targeted effects on carbon ion-induced low-dose hyper-radiosensitivity in MRC-5 cells.

    PubMed

    Ye, Fei; Ning, Jing; Liu, Xinguo; Jin, Xiaodong; Wang, Tieshan; Li, Qiang

    2016-03-01

    Low-dose hyper-radiosensitivity (LDHRS) is a hot topic in normal tissue radiation protection. However, the primary causes for LDHRS still remain unclear. In this study, the impact of non-DNA-targeted effects (NTEs) on high-LET radiation-induced LDHRS was investigated. Human normal lung fibroblast MRC-5 cells were irradiated with high-LET carbon ions, and low-dose biological effects (in terms of various bio-endpoints, including colony formation, DNA damage and micronuclei formation) were detected under conditions with and without gap junctional intercellular communication (GJIC) inhibition. LDHRS was observed when the radiation dose was <0.2 Gy for all bio-endpoints under investigation, but vanished when the GJIC was suppressed. Based on the probability of cells being hit and micro-dose per cell calculation, we deduced that the LDHRS phenomenon came from the combined action of direct hits and NTEs. We concluded that GJIC definitely plays an important role in cytotoxic substance spreading in high-LET carbon ion-induced LDHRS. PMID:26559335

  9. Mask manufacturability improvement by MRC

    NASA Astrophysics Data System (ADS)

    Balasinski, A.; Coburn, D.; Buck, P.

    2007-10-01

    Mask data which can not be properly resolved by the mask writing tools, such as sub(resolution (reticle-scale) features or singularities can interfere with design intent or manufacturing capabilities in the absence of design guidelines or formal verification procedures. As a consequence, mask writing tools may introduce defects to device or metrology structures by snapping geometries to grid or misrepresenting process based sizing. To reduce the visibility of these defects by detuning inspection tools to release the mask with non-resolvable data in the production cycle or by waiving minimum CD rules compromises high fidelity of die pattern transfer to wafer. Driven by poor data quality, mask tool would provide degraded resolution without contextual analysis, such as correlations to the overlying and underlying mask layers and without regard to device models. The key reasons for this situation are arbitrary layout of technology structures and design layout-to-mask post-processing for OPC and fill pattern for which design has no intention or knowledge to intervene. The post-processing of mask data to eliminate errors effectively detaches design responsibility from the mask shop actions and may have other detrimental effects on the production cycle such as iterative defect analysis and long write times due to the large polygon count. In this work we propose mask rule check based on the principles to which the masks are being written and inspected. Running this mandatory rule set should reduce the product cycletime, benefit the cost and improve mask quality and reproduction of design intent. It feeds the prospective mask information back to the layout time making it possible to make design adjustments in the interest of pattern fidelity and device parameters.

  10. Dose intensification in acute myeloid leukaemia: greater effectiveness at lower cost. Principal report of the Medical Research Council's AML9 study. MRC Leukaemia in Adults Working Party.

    PubMed

    Rees, J K; Gray, R G; Wheatley, K

    1996-07-01

    Between 1984 and 1990, 972 patients aged 1-79 years with acute myeloid leukaemia (AML), from 85 British hospitals, were entered into the MRC's 9th AML trial. Patients were randomized between DAT 1 + 5 (daunorubicin for 1 d, with cytarabine and 6-thioguanine for 5 d) and DAT 3 + 10 (same dose drugs for 3 and 10 d respectively) as induction therapy. The 63% who achieved complete remission (CR) were randomized to receive two courses of DAT 2 + 7 alternating with two courses of either MAZE (m-AMSA, 5-azacytidine, etoposide) or COAP (cyclophosphamide, vincristine, cytarabine, prednisone). Finally, those still in CR were randomized to receive either 1 year of maintenance treatment with eight courses of cytarabine and thioguanine followed by four courses of COAP, or no further cytotoxic therapy. Resistance to induction therapy was less common with the DAT 3 + 10 regimen than with DAT 1 + 5 (13% v 23%; P = 0.0001) and hence, despite a 5% increase in the risk of induction death, the CR rate was higher (66% v 61%; P = 0.15). Moreover, CR was achieved more rapidly with DAT 3 + 10 (median 34 v 46 d; P < 0.0001) and thus patients required less time in hospital (mean 20 v 29 d) and less blood product support. 5-year relapse-free survival (28% v 23%; P = 0.05) and survival (23% v 18%; P < 0.05) were also better with DAT 3 + 10. Post-remission intensification of therapy with MAZE resulted in fewer relapses (66% v 74% at 5 years; P = 0.03) but patients allocated MAZE required considerably more supportive care and 14 (4.5%) died following 312 MAZE courses, whereas no deaths occurred following COAP. 5-year survival was not significantly higher with MAZE (37% v 31%). Finally, although 1 year of outpatient maintenance treatment appeared to delay, but not prevent, recurrence it did not improve 5-year survival which was non-significantly worse for those allocated maintenance treatment (41% v 44%). We conclude that the more intensive induction regimen, DAT 3 + 10, is not only more

  11. Impact of adherence to GOLD guidelines on 6-minute walk distance, MRC dyspnea scale score, lung function decline, quality of life, and quality-adjusted life years in a Shanghai suburb.

    PubMed

    Jiang, Y Q; Zhu, Y X; Chen, X L; Xu, X; Li, F; Fu, H J; Shen, C Y; Lu, Y Y; Zhuang, Q J; Xu, G; Cai, Y Y; Zhang, Y; Liu, S S; Zhu, M Y; Li, S H

    2015-01-01

    We performed a 1-year cluster-randomized field trial to assess the effect of standardized management of chronic obstructive pulmonary disease (COPD) on lung function and quality of life (QOL) measures in patients in China. We used the Global Initiative for Chronic Obstructive Lung Disease (GOLD) treatment guidelines and assessed indexes including pulmonary function, QOL, quality-adjusted life years (QALY), Medical Research Council (MRC) dyspnea scale, 6-min walk distance (6-MWD), number of emergency visits, and frequency of hospitalization. Of a total of 711 patients with chronic cough and asthma, 132 were diagnosed as having COPD and 102 participated in this study [intervention group (N = 47); control group (N = 55)]. We found that adherence to GOLD guidelines had a perceivable impact on 6-MWD, MRC dyspnea scale score, and QOL. The average QALY increased by 1.42/person/year in the intervention group, but declined by 0.95/person/year in the control group. We conclude that standardized management improves disease severity, QOL, and QALY in COPD patients when treatment protocols adhere to GOLD guidelines.

  12. Comparison of the amount of bioaccessible fumonisin B1 and B2 in maize and rice inoculated with Fusarium verticillioides (MRC 826) and determined by in vitro digestion-preliminary results.

    PubMed

    Szabó-Fodor, J; Bors, I; Szabó, A; Kovács, M

    2016-08-01

    In this study the occurrence of hidden fumonisin B1 (FB1) and fumonisin B2 (FB2) was analysed, on two cereal substrates (maize and rice), inoculated with Fusarium verticillioides (MRC 826), in order to determine the ratio of hidden FB1 and FB2. Two parallel methods were applied: an in vitro human digestion sample pre-treatment and the routine extraction procedure, in both cases with subsequent LC-MS analysis. It was found that all samples showed higher concentration of total fumonisin B1 after digestion, as compared to that of free fumonisin analysed only after extraction. The percentage of the hidden form by maize was 18.8 % (±2.4) for FB1 and 36.8 % (±3.8) for FB2, while for rice it was 32.3 % (±11.3) and 58.0 (±6.8), respectively, expressed as the proportion to total fumonisin B1, for the total dataset. Significant differences were found in the FB1 and FB2 concentration measured after the different digestion phases (saliva, gastric and duodenal) in case of both matrixes. The results are useful for human risk assessment, since both humans and animals may be exposed to markedly higher toxin load, as determined merely by conventional analytical methods. PMID:27364334

  13. Impact of Radiotherapy When Added to Androgen-Deprivation Therapy for Locally Advanced Prostate Cancer: Long-Term Quality-of-Life Outcomes From the NCIC CTG PR3/MRC PR07 Randomized Trial

    PubMed Central

    Brundage, Michael; Sydes, Matthew R.; Parulekar, Wendy R.; Warde, Padraig; Cowan, Richard; Bezjak, Andrea; Kirkbride, Peter; Parliament, Matthew; Moynihan, Clare; Bahary, Jean-Paul; Parmar, Mahesh K.B.; Sanders, Karen; Chen, Bingshu E.; Mason, Malcolm D.

    2015-01-01

    Purpose The NCIC CTG PR3/MRC PR07 randomized phase III trial compared androgen-deprivation therapy (ADT) alone versus ADT with radiotherapy (RT) for patients with locally advanced prostate cancer. This article reports the health-related quality-of-life (HRQOL) outcomes of this trial. Patients and Methods A total of 1,205 patients were randomly allocated to either ADT alone or ADT with RT. HRQOL was assessed at baseline and every 6 months thereafter using the European Organisation for Research and Treatment of Cancer Core Questionnaire and a prostate cancer–specific checklist or the Functional Assessment of Cancer Therapy–Prostate questionnaire. Mean changes from baseline scores for five function domains and nine symptom domains were analyzed as those most relevant to ADT and RT. The proportions of patients with improved, stable, or worsened HRQOL scores according to instrument-specific minimal important differences were calculated. Results Baseline questionnaires were completed by 1,028 patients (88%). At 6 months, RT had a statistically significant impact on mean score for bowel symptoms (P = .02), diarrhea (P < .001), urinary function (P = .003), and erectile dysfunction (P = .008); by 3 years, however, there were no significant between-group differences in any domain. Generalized linear mixed modeling revealed no significant between-arm differences in any of the function scales but showed significant deterioration in both arms over time for Functional Assessment of Cancer Therapy–Prostate total score, treatment outcome index, and physical and functional well-being. Conclusion The addition of RT to ADT for patients with locally advanced prostate cancer significantly improved overall survival and had only modest and transient negative impact on relevant domains of HRQOL. PMID:26014295

  14. Relationship of Self-Rated Health to Stroke Incidence and Mortality in Older Individuals with and without a History of Stroke: A Longitudinal Study of the MRC Cognitive Function and Ageing (CFAS) Population

    PubMed Central

    Mavaddat, Nahal; van der Linde, Rianne; Parker, Richard; Savva, George; Kinmonth, Ann Louise; Brayne, Carol; Mant, Jonathan

    2016-01-01

    Introduction Poor self-rated health (SRH) has been associated with increased risk of death and poor health outcomes even after adjusting for confounders. However its’ relationship with disease-specific mortality and morbidity has been less studied. SRH may also be particularly predictive of health outcomes in those with pre-existing conditions. We studied whether SRH predicts new stroke in older people who have never had a stroke, or a recurrence in those with a prior history of stroke. Methods MRC CFAS I is a multicentre cohort study of a population representative sample of people in their 65th year and older. A comprehensive interview at baseline included questions about presence of stroke, self-rated health and functional disability. Follow-up at 2 years included self-report of stroke and stroke death obtained from death certificates. Multiple logistical regression determined odds of stroke at 2 years adjusting for confounders including disability and health behaviours. Survival analysis was performed until June 2014 with follow-up for up to 13 years. Results 11,957 participants were included, of whom 11,181 (93.8%) had no history of stroke and 776 (6.2%) one or more previous strokes. Fewer with no history of stroke reported poor SRH than those with stroke (5 versus 21%). In those with no history of stroke, poor self-rated health predicted stroke incidence (OR 1.5 (1.1–1.9)), but not stroke mortality (OR 1.2 (0.8–1.9)) at 2 years nor for up to 13 years (OR 1.2(0.9–1.7)). In those with a history of stroke, self-rated health did not predict stroke incidence (OR 0.9(0.6–1.4)), stroke mortality (OR 1.1(0.5–2.5)), or survival (OR 1.1(0.6–2.1)). Conclusions Poor self-rated health predicts risk of stroke at 2 years but not stroke mortality among the older population without a previous history of stroke. SRH may be helpful in predicting who may be at risk of developing a stroke in the near future. PMID:26928666

  15. Efficacy of systematic pelvic lymphadenectomy in endometrial cancer (MRC ASTEC trial): a randomised study

    PubMed Central

    2009-01-01

    Summary Background Hysterectomy and bilateral salpingo-oophorectomy (BSO) is the standard surgery for stage I endometrial cancer. Systematic pelvic lymphadenectomy has been used to establish whether there is extra-uterine disease and as a therapeutic procedure; however, randomised trials need to be done to assess therapeutic efficacy. The ASTEC surgical trial investigated whether pelvic lymphadenectomy could improve survival of women with endometrial cancer. Methods From 85 centres in four countries, 1408 women with histologically proven endometrial carcinoma thought preoperatively to be confined to the corpus were randomly allocated by a minimisation method to standard surgery (hysterectomy and BSO, peritoneal washings, and palpation of para-aortic nodes; n=704) or standard surgery plus lymphadenectomy (n=704). The primary outcome measure was overall survival. To control for postsurgical treatment, women with early-stage disease at intermediate or high risk of recurrence were randomised (independent of lymph-node status) into the ASTEC radiotherapy trial. Analysis was by intention to treat. This study is registered, number ISRCTN 16571884. Findings After a median follow-up of 37 months (IQR 24–58), 191 women (88 standard surgery group, 103 lymphadenectomy group) had died, with a hazard ratio (HR) of 1·16 (95% CI 0·87–1·54; p=0·31) in favour of standard surgery and an absolute difference in 5-year overall survival of 1% (95% CI −4 to 6). 251 women died or had recurrent disease (107 standard surgery group, 144 lymphadenectomy group), with an HR of 1·35 (1·06–1·73; p=0·017) in favour of standard surgery and an absolute difference in 5-year recurrence-free survival of 6% (1–12). With adjustment for baseline characteristics and pathology details, the HR for overall survival was 1·04 (0·74–1·45; p=0·83) and for recurrence-free survival was 1·25 (0·93–1·66; p=0·14). Interpretation Our results show no evidence of benefit in terms of overall or recurrence-free survival for pelvic lymphadenectomy in women with early endometrial cancer. Pelvic lymphadenectomy cannot be recommended as routine procedure for therapeutic purposes outside of clinical trials. Funding Medical Research Council and National Cancer Research Network. PMID:19070889

  16. Ten-Year Outcomes of First-Episode Psychoses in the MRC ÆSOP-10 Study

    PubMed Central

    Revier, Camice J.; Reininghaus, Ulrich; Dutta, Rina; Fearon, Paul; Murray, Robin M.; Doody, Gillian A.; Croudace, Tim; Dazzan, Paola; Heslin, Margaret; Onyejiaka, Adanna; Kravariti, Eugenia; Lappin, Julia; Lomas, Ben; Kirkbride, James B.; Donoghue, Kim; Morgan, Craig; Jones, Peter B.

    2015-01-01

    Abstract It has long been held that schizophrenia and other psychotic disorders have a predominately poor course and outcome. We have synthesized information on mortality, clinical and social outcomes from the ÆSOP-10 multicenter study, a 10-year follow-up of a large epidemiologically characterized cohort of 557 people with first-episode psychosis. Symptomatic remission and recovery were more common than previously believed. Distinguishing between symptom and social recovery is important given the disparity between these; even when symptomatic recovery occurs social inclusion may remain elusive. Multiple factors were associated with an increased risk of mortality, but unnatural death was reduced by 90% when there was full family involvement at first contact compared with those without family involvement. These results suggest that researchers, clinicians and those affected by psychosis should countenance a much more optimistic view of symptomatic outcome than was assumed when these conditions were first described. PMID:25900547

  17. Ten-Year Outcomes of First-Episode Psychoses in the MRC ÆSOP-10 Study.

    PubMed

    Revier, Camice J; Reininghaus, Ulrich; Dutta, Rina; Fearon, Paul; Murray, Robin M; Doody, Gillian A; Croudace, Tim; Dazzan, Paola; Heslin, Margaret; Onyejiaka, Adanna; Kravariti, Eugenia; Lappin, Julia; Lomas, Ben; Kirkbride, James B; Donoghue, Kim; Morgan, Craig; Jones, Peter B

    2015-05-01

    It has long been held that schizophrenia and other psychotic disorders have a predominately poor course and outcome. We have synthesized information on mortality, clinical and social outcomes from the ÆSOP-10 multicenter study, a 10-year follow-up of a large epidemiologically characterized cohort of 557 people with first-episode psychosis. Symptomatic remission and recovery were more common than previously believed. Distinguishing between symptom and social recovery is important given the disparity between these; even when symptomatic recovery occurs social inclusion may remain elusive. Multiple factors were associated with an increased risk of mortality, but unnatural death was reduced by 90% when there was full family involvement at first contact compared with those without family involvement. These results suggest that researchers, clinicians and those affected by psychosis should countenance a much more optimistic view of symptomatic outcome than was assumed when these conditions were first described. PMID:25900547

  18. Prognostic features in the third MRC myelomatosis trial. Medical Research Council's Working Party on Leukaemia in Adults.

    PubMed Central

    1980-01-01

    This paper reports the prognostic significance of clinical and laboratory features recorded at presentation in 485 patients entered into the Medical Research Council's 3rd therapeutic trial in myelomatosis between July 1975 and August 1978. The data were complete up to 1 January 1980, with a median follow-up time of 36 months. The 3 major determinants of prognosis were the blood urea concentration (BUC), the haemoglobin concentration ([Hb]), and the clinical performance status. Three prognostic groups based on these determinants were specified. The groups contained 22%, 56% and 22% of the patients and gave 2-year survival probabilities of 76%, 50% and 9% respectively. Patients in the good-prognosis group had a BUC less than or equal to 8 mM. [Hb] greater than or equal to 100 g/l, and no or minimal symptoms. Those in the poor-prognosis group had either [Hb] less than or equal to 75 g/l or a BUC greater than 10 mM and restricted clinical activity. Patients who had combinations of the 3 determinant features which excluded them from these 2 groups were classified into an intermediate prognosis group. PMID:7459218

  19. Work-Family Life Courses and Metabolic Markers in the MRC National Survey of Health and Development

    PubMed Central

    Kumari, Meena; Sacker, Amanda; Stafford, Mai; Kuh, Diana; McMunn, Anne

    2016-01-01

    The aim was to investigate whether the combined work-family life courses of British men and women were associated with differences in metabolic markers—waist circumference, blood pressure, high density lipoprotein cholesterol, triglycerides, and glycated haemoglobin—in mid-life. We used data from the Medical Research Council’s National Survey of Health and Development—the 1946 British birth cohort. Multi-channel sequence analysis was used to create a typology of eight work-family life course types combining information on work, partnerships and parenthood between ages 16–51. Linear regression tested associations between work-family types and metabolic outcomes at age 53 on multiply imputed data (20 imputations) of >2,400 participants. Compared with men with strong ties to employment and early transitions to family life, men who made later transitions to parenthood and maintained strong ties to paid work had smaller waist circumferences (-2.16cm, 95% CI: -3.73, -0.59), lower triglycerides (9.78% lower, 95% CI: 0.81, 17.94) and lower blood pressure (systolic: -4.03mmHg, 95% CI: -6.93, -1.13; diastolic: -2.34mmHg, 95% CI: -4.15, -0.53). Married men and women who didn’t have children had increased high density lipoprotein cholesterol (7.23% higher, 95% CI: 0.68, 14.21) and lower waist circumferences (-4.67cm, 95% CI: -8.37, -0.97), respectively. For men later transitions to parenthood combined with strong ties to paid work were linked to reduced metabolic risk in mid-life. Fewer differences between work-family types and metabolic markers were seen for women. PMID:27563726

  20. Recommended minimum data to be collected in research studies on Alzheimer's disease. The MRC (UK) Alzheimer's Disease Workshop Steering Committee.

    PubMed Central

    Wilcock, G K; Hope, R A; Brooks, D N; Lantos, P L; Oppenheimer, C; Reynolds, G P; Rossor, M N; Davies, M B

    1989-01-01

    In order to be able to compare the results of research work carried out in different centres on Alzheimer's disease and dementia, it is necessary for there to be standardised assessment methods. The Medical Research Council organised a workshop in order to see whether workers in Britain in the field of dementia research could agree on such standardised assessment methods. The workshop agreed guidelines for the minimum data which should be collected, in clinical and pathological studies, on patients with presumed Alzheimer's disease and dementia. These recommendations are compared with other approaches based on research diagnostic criteria. PMID:2664087

  1. Work-Family Life Courses and Metabolic Markers in the MRC National Survey of Health and Development.

    PubMed

    Lacey, Rebecca E; Kumari, Meena; Sacker, Amanda; Stafford, Mai; Kuh, Diana; McMunn, Anne

    2016-01-01

    The aim was to investigate whether the combined work-family life courses of British men and women were associated with differences in metabolic markers-waist circumference, blood pressure, high density lipoprotein cholesterol, triglycerides, and glycated haemoglobin-in mid-life. We used data from the Medical Research Council's National Survey of Health and Development-the 1946 British birth cohort. Multi-channel sequence analysis was used to create a typology of eight work-family life course types combining information on work, partnerships and parenthood between ages 16-51. Linear regression tested associations between work-family types and metabolic outcomes at age 53 on multiply imputed data (20 imputations) of >2,400 participants. Compared with men with strong ties to employment and early transitions to family life, men who made later transitions to parenthood and maintained strong ties to paid work had smaller waist circumferences (-2.16cm, 95% CI: -3.73, -0.59), lower triglycerides (9.78% lower, 95% CI: 0.81, 17.94) and lower blood pressure (systolic: -4.03mmHg, 95% CI: -6.93, -1.13; diastolic: -2.34mmHg, 95% CI: -4.15, -0.53). Married men and women who didn't have children had increased high density lipoprotein cholesterol (7.23% higher, 95% CI: 0.68, 14.21) and lower waist circumferences (-4.67cm, 95% CI: -8.37, -0.97), respectively. For men later transitions to parenthood combined with strong ties to paid work were linked to reduced metabolic risk in mid-life. Fewer differences between work-family types and metabolic markers were seen for women. PMID:27563726

  2. A commentary on the NH&MRC Draft Values and Ethics in Aboriginal and Torres Strait Islander Health Research.

    PubMed

    Gillam, Lynn; Pyett, Priscilla

    2003-10-01

    In this paper, we discuss and critically evaluate the National Health and Medical Research Council's recently released document entitled 'Draft Values and Ethics in Aboriginal and Torres Strait Islander Health Research'. We provide a brief account of its development, philosophy and contents, and then consider how the document could be used by HRECs. We recommend that three specially targeted documents be developed from this one document, to meet the particular needs of HRECs, Indigenous people and researchers. We propose a system of Indigenous ethics advisors as a way to implement the central ideas of the new draft guidelines, without falling into the legalism and rule-following that these guidelines explicitly aim to avoid.

  3. Central nervous system involvement in adult acute lymphoblastic leukemia at diagnosis: results from the international ALL trial MRC UKALL XII/ECOG E2993

    PubMed Central

    Lazarus, Hillard M.; Richards, Susan M.; Chopra, Raj; Litzow, Mark R.; Burnett, Alan K.; Wiernik, Peter H.; Franklin, Ian M.; Tallman, Martin S.; Cook, Lucy; Buck, Georgina; Durrant, I. Jill; Rowe, Jacob M.; Goldstone, Anthony H.

    2006-01-01

    Outcome of acute lymphoblastic leukemia (ALL) in adults with central nervous system (CNS) disease at diagnosis is unclear. We treated 1508 de novo ALL patients with 2-phase induction and then high-dose methotrexate with l-asparaginase. Patients up to 50 years old in first remission (CR1) with a matched related donor (MRD) underwent an allogeneic stem cell transplantation (SCT); the remainder in CR1 were randomized to an autologous SCT or intensive consolidation followed by maintenance chemotherapy. Philadelphia chromosome (Ph)–positive patients were offered a matched unrelated donor (MUD) allogeneic SCT. Seventy-seven of 1508 (5%) patients a median age of 29 years had CNS leukemia at presentation; 13 of the 77 (17%) had Ph-positive ALL. Sixty-nine of 77 (90%) patients attained CR1. Thirty-six patients underwent transplantation in CR1 (25 MRD, 5 MUD, and 6 autografts). Eleven of 25 patients with MRD transplantation remain alive at 21 to 102 months, 2 of 5 with MUD at 42 and 71 months, and 1 of 6 with autologous SCT at 35 months. Seven of 27 treated with consolidation/maintenance remain in CR1 56 to 137 months after diagnosis. Overall survival at 5 years was 29% in those with CNS involvement at diagnosis versus 38% (P = .03) for those without. CNS leukemia in adult ALL is uncommon at diagnosis. Adult Ph-negative ALL patients, however, can attain long-term disease-free survival using SCT as well as conventional chemotherapy. PMID:16556888

  4. GoMRC Website ‘Meta-analysis Report: Land-use and submerged aquatic vegetation change in the Gulf of Mexico’

    SciTech Connect

    Judd, Chaeli; Stefansson, Emily S.; Brushnahan, Heather

    2007-12-06

    Over the past century, health and spatial extent of seagrasses has decreased dramatically in the Gulf of Mexico. While some of the changes can be explained by direct impacts to the seagrass beds, we hypothesize that changes in the land use in the watersheds can also be correlated with the decline of seagrasses. Through this meta-analysis, we researched historical and compared trends in seagrass populations and land use in five bays and their watersheds within the Gulf of Mexico: Mobile Bay, Perdido Bay, Tampa Bay, Charlotte Harbor, and Galveston Bay. Using both historical records and spatial datasets, we examined land use and seagrass trends in these five areas.

  5. Induction Chemotherapy and Continuous Hyperfractionated Accelerated Radiotherapy (CHART) for Patients With Locally Advanced Inoperable Non-Small-Cell Lung Cancer: The MRC INCH Randomized Trial

    SciTech Connect

    Hatton, Matthew; Nankivell, Matthew; Lyn, Ethan; Falk, Stephen; Pugh, Cheryl; Navani, Neal; Stephens, Richard; Parmar, Mahesh

    2011-11-01

    Purpose: Recent clinical trials and meta-analyses have shown that both CHART (continuous hyperfractionated accelerated radiation therapy) and induction chemotherapy offer a survival advantage over conventional radical radiotherapy for patients with inoperable non-small cell-lung cancer (NSCLC). This multicenter randomized controlled trial (INCH) was set up to assess the value of giving induction chemotherapy before CHART. Methods and Materials: Patients with histologically confirmed, inoperable, Stage I-III NSCLC were randomized to induction chemotherapy (ICT) (three cycles of cisplatin-based chemotherapy followed by CHART) or CHART alone. Results: Forty-six patients were randomized (23 in each treatment arm) from 9 UK centers. As a result of poor accrual, the trial was closed in December 2007. Twenty-eight patients were male, 28 had squamous cell histology, 34 were Stage IIIA or IIIB, and all baseline characteristics were well balanced between the two treatment arms. Seventeen (74%) of the 23 ICT patients completed the three cycles of chemotherapy. All 42 (22 CHART + 20 ICT) patients who received CHART completed the prescribed treatment. Median survival was 17 months in the CHART arm and 25 months in the ICT arm (hazard ratio of 0.60 [95% CI 0.31-1.16], p = 0.127). Grade 3 or 4 adverse events (mainly fatigue, dysphagia, breathlessness, and anorexia) were reported for 13 (57%) CHART and 13 (65%) ICT patients. Conclusions: This small randomized trial indicates that ICT followed by CHART is feasible and well tolerated. Despite closing early because of poor accrual, and so failing to show clear evidence of a survival benefit for the additional chemotherapy, the results suggest that CHART, and ICT before CHART, remain important options for the treatment of inoperable NSCLC and deserve further study.

  6. Births in Great Britain resulting from assisted conception, 1978-87. MRC Working Party on Children Conceived by In Vitro Fertilisation.

    PubMed Central

    1990-01-01

    OBJECTIVE--To describe the characteristics at birth of children conceived by in vitro fertilisation (IVF) or by gamete intrafallopian transfer (GIFT) and to assess whether they differ from those of children conceived naturally. DESIGN--Survey of children resulting from IVF or GIFT and comparison of their characteristics at birth with national statistics. SETTING--England, Scotland, and Wales from 1978 to 1987. SUBJECTS--1267 Pregnancies conceived by IVF or GIFT, which resulted in 1581 liveborn or stillborn children. MAIN OUTCOME MEASURES--Sex ratio, multiplicity, gestational age at birth, birth weight, stillbirth rate, perinatal and infant mortality, and prevalence of congenital malformations. RESULTS--The ratio of male to female births was 1.07:1; 23% (249/1092) of the deliveries were multiple births compared with 1% for natural conceptions; 24% (278) of 1015 deliveries were preterm compared with 6% in England and Wales; 32% (406) of 1269 babies weighed less than 2500 g compared with 7% in England and Wales. The high percentage of preterm deliveries and of low birthweight babies was largely, but not entirely, due to the high frequency of multiple births. The rate of stillbirth, perinatal mortality, and infant mortality were twice the national average, these excesses being due to the high frequency of multiple births. One or more major congenital malformations were detected during the first week of life in 35 (2.2%) of 1581 babies. This figure is comparable with population based estimates of the prevalence of congenital malformations. The types of malformations reported varied, and the number of each specific type was small. The health of the children was not evaluated beyond the perinatal period. CONCLUSIONS--Multiple pregnancies often result from assisted conception and are the main determinant of the outcome of the pregnancies and of the health of the children at the time of birth. Congenital malformations are comparatively rare, so larger numbers of children need to be studied before firm conclusions can be drawn. The pooling of data from different countries is recommended. PMID:2354290

  7. Breadboard model of a coherent optical BPSK homodyne system with virtual pilot tone (ViP)-based receiver and MRC auxiliary channel

    NASA Astrophysics Data System (ADS)

    David, Florian; Rapp, Christoph

    2000-05-01

    This paper presents a bread-board model of an optical BPSK homodyne system. A new phase synchronization method--the so- called Virtual Pilot-tone method--enables a dramatic reduction of the system completely. Although fully compatible to the transmit signal of a high data rate Costas Loop system, the receiver design is enormously simplified. Neither an optical 90 degree(s) hybrid nor digital high speed electronics are needed. An additional low data rate auxiliary channel is provided by using a Modulated Residual Carrier and envelope detection.The data rate of this auxiliary channel has to be well below that of the main channel, but is sufficient for transmitting e.g. telemetry data. Both methods and their realization are explained. Simulation and practical results are displayed and compared to a standard Costas Loop design.

  8. Preoperative radiotherapy versus selective postoperative chemoradiotherapy in patients with rectal cancer (MRC CR07 and NCIC-CTG C016): a multicentre, randomised trial

    PubMed Central

    Sebag-Montefiore, David; Stephens, Richard J; Steele, Robert; Monson, John; Grieve, Robert; Khanna, Subhash; Quirke, Phil; Couture, Jean; de Metz, Catherine; Myint, Arthur Sun; Bessell, Eric; Griffiths, Gareth; Thompson, Lindsay C; Parmar, Mahesh

    2009-01-01

    Summary Background Preoperative or postoperative radiotherapy reduces the risk of local recurrence in patients with operable rectal cancer. However, improvements in surgery and histopathological assessment mean that the role of radiotherapy needs to be reassessed. We compared short-course preoperative radiotherapy versus initial surgery with selective postoperative chemoradiotherapy. Methods We undertook a randomised trial in 80 centres in four countries. 1350 patients with operable adenocarcinoma of the rectum were randomly assigned, by a minimisation procedure, to short-course preoperative radiotherapy (25 Gy in five fractions; n=674) or to initial surgery with selective postoperative chemoradiotherapy (45 Gy in 25 fractions with concurrent 5-fluorouracil) restricted to patients with involvement of the circumferential resection margin (n=676). The primary outcome measure was local recurrence. Analysis was by intention to treat. This study is registered, number ISRCTN 28785842. Findings At the time of analysis, which included all participants, 330 patients had died (157 preoperative radiotherapy group vs 173 selective postoperative chemoradiotherapy), and median follow-up of surviving patients was 4 years. 99 patients had developed local recurrence (27 preoperative radiotherapy vs 72 selective postoperative chemoradiotherapy). We noted a reduction of 61% in the relative risk of local recurrence for patients receiving preoperative radiotherapy (hazard ratio [HR] 0·39, 95% CI 0·27–0·58, p<0·0001), and an absolute difference at 3 years of 6·2% (95% CI 5·3–7·1) (4·4% preoperative radiotherapy vs 10·6% selective postoperative chemoradiotherapy). We recorded a relative improvement in disease-free survival of 24% for patients receiving preoperative radiotherapy (HR 0·76, 95% CI 0·62–0·94, p=0·013), and an absolute difference at 3 years of 6·0% (95% CI 5·3–6·8) (77·5% vs 71·5%). Overall survival did not differ between the groups (HR 0·91, 95% CI 0·73–1·13, p=0·40). Interpretation Taken with results from other randomised trials, our findings provide convincing and consistent evidence that short-course preoperative radiotherapy is an effective treatment for patients with operable rectal cancer. Funding Medical Research Council (UK) and the National Cancer Institute of Canada. PMID:19269519

  9. A Randomised Phase 2 Trial of Intensive Induction Chemotherapy (CBOP/BEP) and Standard BEP in Poor-prognosis Germ Cell Tumours (MRC TE23, CRUK 05/014, ISRCTN 53643604)

    PubMed Central

    Huddart, Robert A.; Gabe, Rhian; Cafferty, Fay H.; Pollock, Philip; White, Jeff D.; Shamash, Jonathan; Cullen, Michael H.; Stenning, Sally P.

    2015-01-01

    Background Standard chemotherapy for poor-prognosis metastatic nonseminoma has remained bleomycin, etoposide, and cisplatin (BEP) for many years; more effective regimens are required. Objective To explore whether response rates with a new intensive chemotherapy regimen, CBOP/BEP (carboplatin, bleomycin, vincristine, cisplatin/BEP), versus those in concurrent patients treated with standard BEP justify a phase 3 trial. Design, setting, and participants We conducted a phase 2 open-label randomised trial in patients with germ cell tumours of any extracranial primary site and one or more International Germ Cell Cancer Collaborative Group poor-prognosis features. Patients were randomised between 2005 and 2009 at 16 UK centres. Intervention BEP (bleomycin 30 000 IU) was composed of four cycles over 12 wk. CBOP/BEP was composed of 2 × CBOP, 2 × BO, and 3 × BEP (bleomycin 15 000 IU). Outcome measurements and statistical analysis Primary end point was favourable response rate (FRR) comprising complete response or partial response and normal markers. Success required the lower two-sided 90% confidence limit to exclude FRRs <60%; 44 patients on CBOP/BEP gives 90% power to achieve this if the true FRR is ≥80%. Equal numbers were randomised to BEP to benchmark contemporary response rates. Results and limitations A total of 89 patients were randomised (43 CBOP/BEP, 46 BEP); 40 and 41, respectively, completed treatment. CBOP/BEP toxicity, largely haematologic, was high (96% vs 63% on BEP had Common Terminology Criteria for Adverse Events v.3 grade ≥3). FRRs were 74% (90% confidence interval [CI], 61–85) with CBOP/BEP, 61% with BEP (90% CI, 48–73). After a median of 58-mo follow-up, 1-yr progression-free survival (PFS) was 65% and 43%, respectively (hazard ratio: 0.59; 95% CI, 0.33–1.06); 2-yr overall survival (OS) was 67% and 61%. Overall, 3 of 14 CBOP/BEP and 2 of 18 BEP deaths were attributed to toxicity, one after an overdose of bleomycin during CBOP/BEP. The trial was not powered to compare PFS. Conclusions The primary outcome was met, the CI for CBOP/BEP excluding FRRs <61%, but CBOP/BEP was more toxic. PFS and OS data are promising but require confirmation in an international phase 3 trial. Patient summary In this study we tested a new, more intensive way to deliver a combination of drugs often used to treat men with testicular cancer. We found that response rates were higher but that the CBOP/BEP regimen caused more short-term toxicity. Because most patients are diagnosed when their cancer is less advanced, it took twice as long to complete the trial as expected. Although we plan to carry out a larger trial, we will need international collaboration. Trial registration ISRCTN53643604; http://www.controlled-trials.com/ISRCTN53643604. PMID:25001888

  10. A prospective clinicopathologic study of dose-modified CODOX-M/IVAC in patients with sporadic Burkitt lymphoma defined using cytogenetic and immunophenotypic criteria (MRC/NCRI LY10 trial).

    PubMed

    Mead, Graham M; Barrans, Sharon L; Qian, Wendi; Walewski, Jan; Radford, John A; Wolf, Max; Clawson, Simon M; Stenning, Sally P; Yule, Claire L; Jack, Andrew S

    2008-09-15

    This prospective study aimed to develop reproducible diagnostic criteria for sporadic Burkitt lymphoma (BL), applicable to routine practice, and to evaluate the efficacy of dose-modified (dm) CODOX-M/IVAC in patients diagnosed using these criteria. The study was open to patients with an aggressive B-cell lymphoma with an MKI67 fraction approaching 100%. Immunophenotype and fluorescent in situ hybridization (FISH) were used to separate BL from other aggressive B-cell lymphomas. BL was characterized by the presence of a cMYC rearrangement as a sole cytogenetic abnormality occurring in patients with a germinal center phenotype with absence of BCL-2 expression and abnormal TP53 expression. A total of 128 patients were eligible for the study, of whom 58 were considered to have BL and 70 to have diffuse large B-cell lymphoma (DLBCL). There were 110 clinically fit patients who received dmCODOX-M (methotrexate, dose 3 g/m(2)) with or without IVAC according to risk group. The 2-year progression-free survival was 64% (95% confidence interval [CI] 51%-77%) for BL, 55% (95% CI 42%-66%) for DLBCL, 85% (95% CI 73%-97%) for low risk, and 49% (95% CI 38%-60%) for high-risk patients. The observed differences in outcome and other clinical features validate the proposed diagnostic criteria. Compared with the previous trial LY06 with full-dose methotrexate (6.7 g/m(2)), there was a reduction in toxicity with comparable outcomes. This study was registered at www.clinicaltrials.gov as NCT00040690.

  11. Modeling late rectal toxicities based on a parameterized representation of the 3D dose distribution

    NASA Astrophysics Data System (ADS)

    Buettner, Florian; Gulliford, Sarah L.; Webb, Steve; Partridge, Mike

    2011-04-01

    Many models exist for predicting toxicities based on dose-volume histograms (DVHs) or dose-surface histograms (DSHs). This approach has several drawbacks as firstly the reduction of the dose distribution to a histogram results in the loss of spatial information and secondly the bins of the histograms are highly correlated with each other. Furthermore, some of the complex nonlinear models proposed in the past lack a direct physical interpretation and the ability to predict probabilities rather than binary outcomes. We propose a parameterized representation of the 3D distribution of the dose to the rectal wall which explicitly includes geometrical information in the form of the eccentricity of the dose distribution as well as its lateral and longitudinal extent. We use a nonlinear kernel-based probabilistic model to predict late rectal toxicity based on the parameterized dose distribution and assessed its predictive power using data from the MRC RT01 trial (ISCTRN 47772397). The endpoints under consideration were rectal bleeding, loose stools, and a global toxicity score. We extract simple rules identifying 3D dose patterns related to a specifically low risk of complication. Normal tissue complication probability (NTCP) models based on parameterized representations of geometrical and volumetric measures resulted in areas under the curve (AUCs) of 0.66, 0.63 and 0.67 for predicting rectal bleeding, loose stools and global toxicity, respectively. In comparison, NTCP models based on standard DVHs performed worse and resulted in AUCs of 0.59 for all three endpoints. In conclusion, we have presented low-dimensional, interpretable and nonlinear NTCP models based on the parameterized representation of the dose to the rectal wall. These models had a higher predictive power than models based on standard DVHs and their low dimensionality allowed for the identification of 3D dose patterns related to a low risk of complication.

  12. Magnetic resonance cholangiography: applications in patients with calculus disease of the biliary tract.

    PubMed

    Liu, Terrence H; Organ, Claude H

    2004-04-01

    Magnetic resonance cholangiography (MRC) is a non-invasive imaging modality that has become widely available. In the short time since its introduction, MRC has been shown to possess excellent accuracy for the diagnosis of various biliary pathologies, including choledocholithiasis. Investigations of the clinical applications of MRC are ongoing. This review summarizes the diagnostic capabilities of MRC and discusses its application in the management of patients with gallstone diseases.

  13. Impact Evaluation of the Minnesota Reading Corps K-3 Program

    ERIC Educational Resources Information Center

    Markovitz, Carrie E.; Hernandez, Marc W.; Hedberg, Eric C.; Silberglitt, Benjamin

    2014-01-01

    Minnesota Reading Corps (MRC) is the largest AmeriCorps State program in the country. The goal of MRC is to ensure that students become successful readers and meet reading proficiency targets by the end of the third grade. To meet this goal, the MRC program, and its host organization, ServeMinnesota Action Network, recruit, train, place and…

  14. Evolution of an Expanded Mannose Receptor Gene Family

    PubMed Central

    Staines, Karen; Hunt, Lawrence G.; Young, John R.; Butter, Colin

    2014-01-01

    Sequences of peptides from a protein specifically immunoprecipitated by an antibody, KUL01, that recognises chicken macrophages, identified a homologue of the mammalian mannose receptor, MRC1, which we called MRC1L-B. Inspection of the genomic environment of the chicken gene revealed an array of five paralogous genes, MRC1L-A to MRC1L-E, located between conserved flanking genes found either side of the single MRC1 gene in mammals. Transcripts of all five genes were detected in RNA from a macrophage cell line and other RNAs, whose sequences allowed the precise definition of spliced exons, confirming or correcting existing bioinformatic annotation. The confirmed gene structures were used to locate orthologues of all five genes in the genomes of two other avian species and of the painted turtle, all with intact coding sequences. The lizard genome had only three genes, one orthologue of MRC1L-A and two orthologues of the MRC1L-B antigen gene resulting from a recent duplication. The Xenopus genome, like that of most mammals, had only a single MRC1-like gene at the corresponding locus. MRC1L-A and MRC1L-B genes had similar cytoplasmic regions that may be indicative of similar subcellular migration and functions. Cytoplasmic regions of the other three genes were very divergent, possibly indicating the evolution of a new functional repertoire for this family of molecules, which might include novel interactions with pathogens. PMID:25390371

  15. Medical reserve corps volunteers in disasters: a survey of their roles, experiences, and challenges.

    PubMed

    Watson, Matthew; Selck, Frederic; Rambhia, Kunal; Morhard, Ryan; Franco, Crystal; Toner, Eric

    2014-01-01

    The Medical Reserve Corps (MRC) was established in the Office of the Surgeon General in response to the spontaneous but disorganized outpouring of medical volunteers following the terrorist attacks of 2001. The mission of the federal MRC office is to provide organizational structure and guidance to the nearly 1,000 locally organized and funded MRC units that have grown up across the country and the more than 200,000 volunteer health professionals that staff these units. Despite the large size of this program and its numerous activations over the past decade, including in the Boston Marathon bombing and Hurricane Sandy, relatively little is known about the MRC, including the make-up of the units, the ways units have been used, and the challenges faced by MRC units and their volunteers. Here we report the results of a mixed-methods investigation of MRC unit organization, activities, and challenges. PMID:24697751

  16. Explosive safety criteria at a Department of Energy contractor facility

    SciTech Connect

    Krach, F.

    1984-08-01

    Monsanto Research Corporation (MRC) operates the Mound facility in Miamisburg, Ohio, for the Department of Energy. Small explosive components are manufactured at MRC, and stringent explosive safety criteria have been developed for their manufacturing. The goals of these standards are to reduce employee injuries and eliminate fenceline impacts resulting from accidental detonations. This paper will describe the manner in which these criteria were developed and what DOD standards were incorporated into MRC's own design criteria. These design requirements are applicable to all new construction at MRC. An example of the development of the design of a Component Test Facility will be presented to illustrate the application of the criteria.

  17. Explosive safety criteria at a Department of Energy contractor facility

    NASA Astrophysics Data System (ADS)

    Krach, F.

    1984-08-01

    Monsanto Research Corporation (MRC) operates the Mound facility in Miamisburg, Ohio, for the Department of Energy. Small explosive components are manufactured at MRC, and stringent explosive safety criteria have been developed for their manufacturing. The goals of these standards are to reduce employee injuries and eliminate fenceline impacts resulting from accidental detonations. The manner in which these criteria were developed and what DOD standards were incorporated into MRC's own design criteria are described. These design requirements are applicable to all new construction at MRC. An example of the development of the design of a Component Test Facility is presented to illustrate the application of the criteria.

  18. Mutagenicity in Salmonella of a Simulated Urban-Smog Atmosphere Generated Using a Mobile Reaction Chamber

    EPA Science Inventory

    The EPA Mobile Reaction Chamber (MRC) is a 24-foot trailer containing a 14.3-m3 Teflon lined photochemical chamber used to generate simulated urban atmospheres. Photochemistry in the MRC is catalyzed by 120 fluorescent bulbs evenly mixed with black light bulbs and UV bulbs (300 &...

  19. 78 FR 59994 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-30

    ... Regarding Public Directors and the Process for Designating Membership/Risk Committee Members September 24...-Laws and Rules to make structural changes to OCC's Membership/Risk Committee (``MRC'') regarding Public... nominate one of the Public Directors to serve as the MRC Chairman. \\4\\ In relevant part, Article...

  20. Age-related changes in tissue macrophages precede cardiac functional impairment.

    PubMed

    Pinto, Alexander R; Godwin, James W; Chandran, Anjana; Hersey, Lucy; Ilinykh, Alexei; Debuque, Ryan; Wang, Lina; Rosenthal, Nadia A

    2014-05-01

    Cardiac tissue macrophages (cTMs) are abundant in the murine heart but the extent to which the cTM phenotype changes with age is unknown. This study characterizes aging-dependent phenotypic changes in cTM subsets. Using theCx3cr1(GFP/+) mouse reporter line where GFP marks cTMs, and the tissue macrophage marker Mrc1, we show that two major cardiac tissue macrophage subsets, Mrc1-GFP(hi) and Mrc1+GFP(hi) cTMs, are present in the young (<10 week old) mouse heart, and a third subset, Mrc1+GFP(lo), comprises ~50% of total Mrc1+ cTMs from 30 weeks of age. Immunostaining and functional assays show that Mrc1+ cTMs are the principal myeloid sentinels in the mouse heart and that they retain proliferative capacity throughout life. Gene expression profiles of the two Mrc1+ subsets also reveal that Mrc1+GFP(lo) cTMs have a decreased number of immune response genes (Cx3cr1, Lpar6, CD9, Cxcr4, Itga6 and Tgfβr1), and an increased number of fibrogenic genes (Ltc4s, Retnla, Fgfr1, Mmp9 and Ccl24), consistent with a potential role for cTMs in cardiac fibrosis. These findings identify early age-dependent gene expression changes in cTMs, with significant implications for cardiac tissue injury responses and aging-associated cardiac fibrosis. PMID:24861132

  1. Using pedotransfer functions to estimate the van Genuchten-Mualem soil hydraulic properties: A review

    Technology Transfer Automated Retrieval System (TEKTRAN)

    In this paper, we review the use of the van Genuchten Mualem (VGM) model to parameterize the soil moisture retention characteristic (MRC) and the nsaturated hydraulic conductivity curve (HCC), as well as its use in developing pedotransfer functions (PFTs). Analysis of literature data showed that MRC...

  2. Attentional Demands on Motor-Respiratory Coordination

    ERIC Educational Resources Information Center

    Hessler, Eric E.; Amazeen, Polemnia G.

    2009-01-01

    Athletic performance requires the pacing of breathing with exercise, known as motor-respiratory coordination (MRC). In this study, we added cognitive and physical constraints while participants intentionally controlled their breathing locations during rhythmic arm movement. This is the first study to examine a cognitive constraint on MRC.…

  3. The Relative Importance of Children's Criteria for Representational Adequacy in the Perception of Simple Sonic Stimuli

    ERIC Educational Resources Information Center

    Verschaffel, Lieven; Reybrouck, Mark; Degraeuwe, Goedele; Van Dooren, Wim

    2013-01-01

    This study investigates children's metarepresentational competence (MRC) with regard to listening to and making sense of simple sonic stimuli. Using diSessa's (2002) seminal work on MRC in mathematics and sciences as background, it aims to assess the relative importance children attribute to several criteria for representational adequacy…

  4. Impact Evaluation: Minnesota Reading Corps K-3 Program. Appendices

    ERIC Educational Resources Information Center

    Markovitz, Carrie E.; Hernandez, Marc W.; Hedberg, Eric C.; Silberglitt, Benjamin

    2014-01-01

    Minnesota Reading Corps (MRC) is the largest AmeriCorps State program in the country. The goal of MRC is to ensure that students become successful readers and meet reading proficiency targets by the end of the third grade. Starting in 2011, the "Corporation for National and Community Service" (CNCS) sponsored a randomized controlled…

  5. Autoimmunity and aging: the age-related response of mice of a long-lived strain to trinitrophenylated syngeneic mouse red blood cells.

    PubMed

    Naor, D; Bonavida, B; Walford, R L

    1976-12-01

    Mice of 1.5, 9, 22, and 31 to 32 months of age were injected with the thymus-dependent antigen, TNP-SRC, or the thymus-independent antigen, TNP-SRC, TNP-MRC. The anti-SRC and TNP immune responses to TNP-SRC were markedly reduced in older mice, whereas the anti-TNP response to the TNP-MRC showed no substantial decline. Young mice produced higher anti-TNP plaque-forming cell responses after injection of TNP-SRC than after TNP-MRC, whereas in older mice the reverse obtained. Old mice but not young mice displayed a high anti-SRC cross-reactive response after injection of TNP-MRC. The avidity of anti-TNP antibody of young mice immunized with TNP-SRC was higher than that following immunization with TNP-MRC, whereas the avidities of anti-TNP antibodies from old mice injected with these two reagents were the same. Those individual mice which showed a poorly regulated immune response also displayed an autologous anti-MRC plaque-forming cell response after injection of either TNP-SRC or TNP-MRC. It is suggested that mechanisms mediated by suppressor T cells may be responsible for regulating the autoimmune response to modified self antigens, and that these are severely impaired in age individuals.

  6. Evaluation of Laser Stabilization and Imaging Systems for LCLS-II - Oral Presentation

    SciTech Connect

    Barry, Matthew

    2015-08-19

    This presentation covers data collected on two commercial laser stabilization systems, Guidestar-II and MRC, and two optical imaging systems. Additionally, general information about LCLS-II and how to go about continuing-testing is covered.

  7. Upward Altitudinal Shifts in Habitat Suitability of Mountain Vipers since the Last Glacial Maximum

    PubMed Central

    Yousefi, Masoud; Ahmadi, Mohsen; Nourani, Elham; Behrooz, Roozbeh; Rajabizadeh, Mehdi; Geniez, Philippe; Kaboli, Mohammad

    2015-01-01

    We determined the effects of past and future climate changes on the distribution of the Montivipera raddei species complex (MRC) that contains rare and endangered viper species limited to Iran, Turkey and Armenia. We also investigated the current distribution of MRC to locate unidentified isolated populations as well as to evaluate the effectiveness of the current network of protected areas for their conservation. Present distribution of MRC was modeled based on ecological variables and model performance was evaluated by field visits. Some individuals at the newly identified populations showed uncommon morphological characteristics. The distribution map of MRC derived through modeling was then compared with the distribution of protected areas in the region. We estimated the effectiveness of the current protected area network to be 10%, which would be sufficient for conserving this group of species, provided adequate management policies and practices are employed. We further modeled the distribution of MRC in the past (21,000 years ago) and under two scenarios in the future (to 2070). These models indicated that climatic changes probably have been responsible for an upward shift in suitable habitats of MRC since the Last Glacial Maximum, leading to isolation of allopatric populations. Distribution will probably become much more restricted in the future as a result of the current rate of global warming. We conclude that climate change most likely played a major role in determining the distribution pattern of MRC, restricting allopatric populations to mountaintops due to habitat alterations. This long-term isolation has facilitated unique local adaptations among MRC populations, which requires further investigation. The suitable habitat patches identified through modeling constitute optimized solutions for inclusion in the network of protected areas in the region. PMID:26367126

  8. After slow start, project to channel drug company funds to universities builds steam.

    PubMed

    Berkowitz, P

    1996-08-01

    Drug companies appear to have been listening when researchers began complaining about their lack of participation in the MRC/PMAC Health Program, for the 30-month-old project appears to have taken on new life. It is designed to increase collaboration between university and pharmaceutical industry researchers by directing more of the industry's growing investment in Canada through the MRC's peer-review process. By mid-May, program commitments stood at $60 million.

  9. Performance characteristics of magnetic resonance cholangiography in the staging of malignant hilar strictures

    PubMed Central

    Zidi, S; Prat, F; Le Guen, O; Rondeau, Y; Pelletier, G

    2000-01-01

    BACKGROUND—Magnetic resonance cholangiography (MRC) is currently under investigation for non-invasive biliary tract imaging.
AIM—To compare MRC with endoscopic retrograde cholangiography (ERC) for pretreatment evaluation of malignant hilar obstruction.
METHODS—Twenty patients (11 men, nine women; median age 74 years) referred for endoscopic palliation of a hilar obstruction were included. The cause of the hilar obstruction was a cholangiocarcinoma in 15 patients and a hilar compression in five (one hepatocarcinoma, one metastatic breast cancer, one metastatic leiomyoblastoma, two metastatic colon cancers). MRC (T2 turbo spin echo sequences; Siemens Magnetomvision 1.5 T) was performed within 12 hours before ERC, which is considered to be the ideal imaging technique. Tumour location, extension, and type according to Bismuth's classification were determined by the radiologist and endoscopist.
RESULTS—MRC was of diagnostic quality in all but two patients (90%). At ERC, four patients (20%) had type I, seven (35%) had type II, seven (35%) had type III, and two (10%) had type IV strictures. MRC correctly classified 14/18 (78%) patients and underestimated tumour extension in four (22%). Successful endoscopic biliary drainage was achieved in 11/17 attempted stentings (65%), one of which was a combined procedure (endoscopic + percutaneous). One patient had a percutaneous external drain, one had a surgical bypass, and in a third a curative resection was attempted. Effective drainage was not achieved in six patients (30%). If management options had been based only on MRC, treatment choices would have been modified in a more appropriate way in 5/18 (28%) patients with satisfactory MRC.
CONCLUSION—MRC should be considered for planning treatment of malignant hilar strictures. Accurate depiction of high grade strictures for which endoscopic drainage is not the option of choice can preclude unnecessary invasive imaging.


Keywords: hilar tumours

  10. Scrotal pearl is not always a sign of anorectal malformation: median raphe cyst.

    PubMed

    Soyer, Tutku; Karabulut, Ayşe Anıl; Boybeyi, Özlem; Günal, Yasemin Dere

    2013-01-01

    Pearls of meconium can be seen on the raphe of the scrotum and are considered as a sign of anorectal malformation (ARM). Scrotal pearls without ARM are rare in children and designated as median raphe cyst of the scrotum (MRC). A six-month-old boy with scrotal pearls without ARM is presented to discuss the clinical features and treatment modalities of MRC in infants. PMID:24577992

  11. Specific requirements of nonbilayer phospholipids in mitochondrial respiratory chain function and formation

    PubMed Central

    Baker, Charli D.; Basu Ball, Writoban; Pryce, Erin N.; Gohil, Vishal M.

    2016-01-01

    Mitochondrial membrane phospholipid composition affects mitochondrial function by influencing the assembly of the mitochondrial respiratory chain (MRC) complexes into supercomplexes. For example, the loss of cardiolipin (CL), a signature non–bilayer-forming phospholipid of mitochondria, results in disruption of MRC supercomplexes. However, the functions of the most abundant mitochondrial phospholipids, bilayer-forming phosphatidylcholine (PC) and non–bilayer-forming phosphatidylethanolamine (PE), are not clearly defined. Using yeast mutants of PE and PC biosynthetic pathways, we show a specific requirement for mitochondrial PE in MRC complex III and IV activities but not for their formation, whereas loss of PC does not affect MRC function or formation. Unlike CL, mitochondrial PE or PC is not required for MRC supercomplex formation, emphasizing the specific requirement of CL in supercomplex assembly. Of interest, PE biosynthesized in the endoplasmic reticulum (ER) can functionally substitute for the lack of mitochondrial PE biosynthesis, suggesting the existence of PE transport pathway from ER to mitochondria. To understand the mechanism of PE transport, we disrupted ER–mitochondrial contact sites formed by the ERMES complex and found that, although not essential for PE transport, ERMES facilitates the efficient rescue of mitochondrial PE deficiency. Our work highlights specific roles of non–bilayer-forming phospholipids in MRC function and formation. PMID:27226479

  12. Dyspnea as a Prognostic Factor in Patients with Non-Small Cell Lung Cancer

    PubMed Central

    Ban, Wooho; Lee, Jong Min; Ha, Jick Hwan; Yeo, Chang Dong; Kang, Hyeon Hui; Rhee, Chin Kook; Moon, Hwa Sik

    2016-01-01

    Purpose To investigate associations between dyspnea and clinical outcomes in patients with non-small cell lung cancer (NSCLC). Materials and Methods From 2001 to 2014, we retrospectively reviewed the prospective lung cancer database of St. Paul's Hospital at the Catholic University of Korea. We enrolled patients with NSCLC and evaluated symptoms of dyspnea using modified Medical Research Council (mMRC) scores. Also, we estimated pulmonary functions and analyzed survival data. Results In total, 457 NSCLC patients were enrolled, and 259 (56.7%) had dyspnea. Among those with dyspnea and whose mMRC scores were available (109 patients had no mMRC score), 85 (56.6%) patients had an mMRC score <2, while 65 (43.3%) had an mMRC score ≥2. Significant decreased pulmonary functions were observed in patients with dyspnea. In multivariate analysis, aging, poor performance status, advanced stage, low forced expiratory volume in 1 second (%), and an mMRC score ≥2 were found to be significant prognostic factors for patient survival. Conclusion Dyspnea could be a significant prognostic factor in patients with NSCLC. PMID:27401635

  13. Simple and versatile molecular method of copy-number measurement using cloned competitors.

    PubMed

    Kim, Hyun-Kyoung; Hwang, Hai-Li; Park, Seong-Yeol; Lee, Kwang Man; Park, Won Cheol; Kim, Han-Seong; Um, Tae-Hyun; Hong, Young Jun; Lee, Jin Kyung; Joo, Sun-Young; Seoh, Ju-Young; Song, Yeong-Wook; Kim, Soo-Youl; Kim, Yong-Nyun; Hong, Kyeong-Man

    2013-01-01

    Variations and alterations of copy numbers (CNVs and CNAs) carry disease susceptibility and drug responsiveness implications. Although there are many molecular methods to measure copy numbers, sensitivity, reproducibility, cost, and time issues remain. In the present study, we were able to solve those problems utilizing our modified real competitive PCR method with cloned competitors (mrcPCR). First, the mrcPCR for ERBB2 copy number was established, and the results were comparable to current standard methods but with a shorter assay time and a lower cost. Second, the mrcPCR assays for 24 drug-target genes were established, and the results in a panel of NCI-60 cells were comparable to those from real-time PCR and microarray. Third, the mrcPCR results for FCGR3A and the FCGR3B CNVs were comparable to those by the paralog ratio test (PRT), but without PRT's limitations. These results suggest that mrcPCR is comparable to the currently available standard or the most sensitive methods. In addition, mrcPCR would be invaluable for measurement of CNVs in genes with variants of similar structures, because combination of the other methods is not necessary, along with its other advantages such as short assay time, small sample amount requirement, and applicability to all sequences and genes.

  14. Analysis And Synthesis Of Model Reference Controller For Variable Speed Wind Generators Inertial Support

    NASA Astrophysics Data System (ADS)

    Bećirović, Elvisa; Osmić, Jakub; Kušljugić, Mirza; Perić, Nedjeljko

    2015-01-01

    Model Reference Controller (MRC) for contribution of Variable Speed Wind Generators (VSWG) in inertial response of Electrical Power System (EPS) is presented and analyzed in this paper. MRC is synthesized based on a model of Generating Unit With non-Reheat Steam Turbine (GUNRST) thus enabling VSWG to emulate GUNRST response during the initial stage of dynamic frequency response ie inertial phase. Very important property of conventional steam generating units is that its contribution to inertial phase response is independent from the initial generating power. By using MRC in VSWG it is accomplished that in most common wind speed region (3-12 m/s) VSWG inertial support is almost independent from wind speed. Since in most EPSs VSWG replaces conventional steam generators, application of MRC algorithm provides that the characteristics of EPS in terms of inertial response are preserved, regardless of the growing trend of introducing VSWG. Evaluation analysis of the proposed MRC is performed on modified nine bus power system when VSWG with MRC is connected to one of the power system buses.

  15. Simple and Versatile Molecular Method of Copy-Number Measurement Using Cloned Competitors

    PubMed Central

    Kim, Hyun-Kyoung; Hwang, Hai-Li; Park, Seong-Yeol; Lee, Kwang Man; Park, Won Cheol; Kim, Han-Seong; Um, Tae-Hyun; Hong, Young Jun; Lee, Jin Kyung; Joo, Sun-Young; Seoh, Ju-Young; Song, Yeong-Wook; Kim, Soo-Youl; Kim, Yong-Nyun; Hong, Kyeong-Man

    2013-01-01

    Variations and alterations of copy numbers (CNVs and CNAs) carry disease susceptibility and drug responsiveness implications. Although there are many molecular methods to measure copy numbers, sensitivity, reproducibility, cost, and time issues remain. In the present study, we were able to solve those problems utilizing our modified real competitive PCR method with cloned competitors (mrcPCR). First, the mrcPCR for ERBB2 copy number was established, and the results were comparable to current standard methods but with a shorter assay time and a lower cost. Second, the mrcPCR assays for 24 drug-target genes were established, and the results in a panel of NCI-60 cells were comparable to those from real-time PCR and microarray. Third, the mrcPCR results for FCGR3A and the FCGR3B CNVs were comparable to those by the paralog ratio test (PRT), but without PRT's limitations. These results suggest that mrcPCR is comparable to the currently available standard or the most sensitive methods. In addition, mrcPCR would be invaluable for measurement of CNVs in genes with variants of similar structures, because combination of the other methods is not necessary, along with its other advantages such as short assay time, small sample amount requirement, and applicability to all sequences and genes. PMID:23936009

  16. The Rhizome Mixture of Anemarrhena asphodeloides and Coptis chinensis Attenuates Mesalazine-Resistant Colitis in Mice

    PubMed Central

    Lim, Su-Min; Choi, Hyun Sik; Jeong, Jin-Ju; Han, Seung-Won

    2016-01-01

    We investigated the effect of DWac on the gut microbiota composition in mice with 2,3,6-trinitrobenzenesulfonic acid- (TNBS-) induced colitis. Treatment with DWac restored TNBS-disturbed gut microbiota composition and attenuated TNBS-induced colitis. Moreover, we examined the effect of DWac in mice with mesalazine-resistant colitis (MRC). Intrarectal injection of TNBS in MRC mice caused severe colitis, as well as colon shortening, edema, and increased myeloperoxidase activity. Treatment with mesalazine (30 mg/kg) did not attenuate TNBS-induced colitis in MRC mice, whereas treatment with DWac (30 mg/kg) significantly attenuated TNBS-induced colitis. Moreover, treatment with the mixture of mesalazine (15 mg/kg) and DWac (15 mg/kg) additively attenuated colitis in MRC mice. Treatment with DWac and its mixture with mesalazine inhibited TNBS-induced activation of NF-κB and expression of M1 macrophage markers but increased TNBS-suppressed expression of M2 macrophage markers. Furthermore, these inhibited TNBS-induced T-bet, RORγt, TNF-α, and IL-17 expression but increased TNBS-suppressed Foxp3 and IL-10 expression. However, Th2 cell differentiation and GATA3 and IL-5 expression were not affected. These findings suggest that DWac can ameliorate MRC by increasing the polarization of M2 macrophage and correcting the disturbance of gut microbiota and Th1/Th17/Treg, as well as additively attenuating MRC along with mesalazine. PMID:27761147

  17. Optimization of mask manufacturing rule check constraint for model based assist feature generation

    NASA Astrophysics Data System (ADS)

    Shim, Seongbo; Kim, Young-chang; Chun, Yong-jin; Lee, Seong-Woo; Lee, Suk-joo; Choi, Seong-woon; Han, Woo-sung; Chang, Seong-hoon; Yoon, Seok-chan; Kim, Hee-bom; Ki, Won-tai; Woo, Sang-gyun; Cho, Han-gu

    2008-11-01

    SRAF (sub-resolution assist feature) generation technology has been a popular resolution enhancement technique in photo-lithography past sub-65nm node. It helps to increase the process window, and these are some times called ILT(inverse lithography technology). Also, many studies have been presented on how to determine the best positions of SRAFs, and optimize its size. According to these reports, the generation of SRAF can be formulated as a constrained optimization problem. The constraints are the side lobe suppression and allowable minimum feature size or MRC (mask manufacturing rule check). As we know, bigger SRAF gives better contribution to main feature but susceptible to SRAF side lobe issue. Thus, we finally have no choice but to trade-off the advantages of the ideally optimized mask that contains very complicated SRAF patterns to the layout that has been MRC imposed applied to it. The above dilemma can be resolved by simultaneously using lower dose (high threshold) and cleaning up by smaller MRC. This solution makes the room between threshold (side lobe limitation) and MRC constraint (minimum feature limitation) wider. In order to use smaller MRC restriction without considering the mask writing and inspection issue, it is also appropriate to identify the exact mask writing limitation and find the smart mask constraints that well reflect the mask manufacturability and the e-beam lithography characteristics. In this article, we discuss two main topics on mask optimizations with SRAF. The first topic is on the experimental work to find what behavior of the mask writing ability is in term of several MRC parameters, and we propose more effective MRC constraint for aggressive generation of SRAF. The next topic is on finding the optimum MRC condition in practical case, 3X nm node DRAM contact layer. In fact, it is not easy to encompass the mask writing capability for very complicate real SRAF pattern by using the current MRC constraint based on the only width and

  18. MIDWESTERN REGIONAL CENTER OF THE DOE NATIONAL INSTITUTE FOR CLIMATIC CHANGE RESEARCH

    SciTech Connect

    Burton, Andrew J.

    2014-02-28

    The goal of NICCR (National Institute for Climatic Change Research) was to mobilize university researchers, from all regions of the country, in support of the climatic change research objectives of DOE/BER. The NICCR Midwestern Regional Center (MRC) supported work in the following states: North Dakota, South Dakota, Nebraska, Kansas, Oklahoma, Minnesota, Iowa, Missouri, Wisconsin, Illinois, Michigan, Indiana, and Ohio. The MRC of NICCR was able to support nearly $8 million in climatic change research, including $6,671,303 for twenty projects solicited and selected by the MRC over five requests for proposals (RFPs) and $1,051,666 for the final year of ten projects from the discontinued DOE NIGEC (National Institute for Global Environmental Change) program. The projects selected and funded by the MRC resulted in 135 peer-reviewed publications and supported the training of 25 PhD students and 23 Masters students. Another 36 publications were generated by the final year of continuing NIGEC projects supported by the MRC. The projects funded by the MRC used a variety of approaches to answer questions relevant to the DOE’s climate change research program. These included experiments that manipulated temperature, moisture and other global change factors; studies that sought to understand how the distribution of species and ecosystems might change under future climates; studies that used measurements and modeling to examine current ecosystem fluxes of energy and mass and those that would exist under future conditions; and studies that synthesized existing data sets to improve our understanding of the effects of climatic change on terrestrial ecosystems. In all of these efforts, the MRC specifically sought to identify and quantify responses of terrestrial ecosystems that were not well understood or not well modeled by current efforts. The MRC also sought to better understand and model important feedbacks between terrestrial ecosystems, atmospheric chemistry, and regional

  19. Diversity technique for DAPSK signal over the frequency-selective fading channel

    NASA Astrophysics Data System (ADS)

    Lee, Jong Y.; Chung, Young M.; Lee, Sang U.

    2001-10-01

    In this paper, a maximal ratio combining (MRC) and weighted maximal ratio combining (WMRC) diversity receiver are proposed. The MRC receiver makes a decision at each branch based on the minimum distance criterion. The performance of the MRC receiver is analyzed on the frequency-selective Rayleigh and Rician fading channels, in terms of the union bound for bit error probability. In addition, the WMRC receiver, which assigns weighting factors to the decision variable at each branch, based on the optimum decision boundaries, is proposed. The performance of the WMRC is investigated through the computer simulation and compared with those of MRC and equal gain combining (EGC). From the results, it is found that the performances of the WMRC and MRC are better than those of EGC on both the frequency-selective Rayleigh and Rician fading channels and performance improvements over the EGC are noticeable when the number of diversity branches is large as long as the root mean square (rms) delay is smaller than or equal to 10% of the symbol period.

  20. Prescriptions for medical research. I--Management within the Medical Research Council.

    PubMed Central

    Gillett, R; Harrow, J

    1993-01-01

    In their submission to the government in advance of the white paper on science policy in the United Kingdom the Medical Research Council commends the MRC's own approach to managing directly funded research. But a series of semi-structured interviews with the directors of some of the MRC's units suggests a gap between the MRC's model of managed research and the reality. Although such units are theoretically managed from MRC head office (and units are charged an overhead for this), in practice each unit runs its own affairs. Between major reviews average contact time with the head office contact person is seven hours a year. The first paper argues that a purchaser-provider split would recognise the benefits of decentralisation and allow units to bid for research funds from several sources, the successful ones guaranteeing their survival through a rolling series of research programmes. The second paper criticises the MRC's cumbersome peer review system. Reliance on outside experts atrophies the scientific skills of head office staff and builds delays into decision making. A purchaser-provider model would allow the head office scientific staff to act like commercial research and development managers, commissioning research, and using the outcome, rather than peer review, as a criterion for continued funding. PMID:8324441

  1. Leaf cuticular wax amount and crystal morphology regulate post-harvest water loss in mulberry (Morus species).

    PubMed

    Mamrutha, H M; Mogili, T; Jhansi Lakshmi, K; Rama, N; Kosma, Dylan; Udaya Kumar, M; Jenks, Matthew A; Nataraja, Karaba N

    2010-08-01

    Mulberry leaves are the sole source of food for silkworms (Bombyx mori), and moisture content of the detached leaves fed to silkworms determines silkworm growth and cocoon yield. Since leaf dehydration in commercial sericulture is a serious problem, development of new methods that minimize post-harvest water loss are greatly needed. In the present study, variability in moisture retention capacity (MRC, measured as leaf relative water content after one to 5 h of air-drying) was examined by screening 290 diverse mulberry accessions and the relationship between MRC and leaf surface (cuticular) wax amount was determined. Leaf MRC varied significantly among accessions, and was found to correlate strongly with leaf wax amount. Scanning electron microscopic analysis indicated that leaves having crystalline surface waxes of increased facet size and density were associated with high MRC accessions. Leaf MRC at 5 h after harvest was not related to other parameters such as specific leaf weight, and stomatal frequency and index. This study suggests that mulberry accessions having elevated leaf surface wax amount and crystal size and density exhibit reduced leaf post-harvest water loss, and could provide the foundation for selective breeding of improved cultivars. PMID:20580887

  2. Performance analysis of satellite-to-ground downlink coherent optical communications with spatial diversity over Gamma-Gamma atmospheric turbulence.

    PubMed

    Ma, Jing; Li, Kangning; Tan, Liying; Yu, Siyuan; Cao, Yubin

    2015-09-01

    The performances of satellite-to-ground downlink optical communications over Gamma-Gamma distributed atmospheric turbulence are studied for a coherent detection receiving system with spatial diversity. Maximum ratio combining (MRC) and selection combining (SC) techniques are considered as practical schemes to mitigate the atmospheric turbulence. Bit-error rate (BER) performances for binary phase-shift keying modulated coherent detection and outage probabilities are analyzed and compared for SC diversity using analytical results and for MRC diversity through an approximation method with different numbers of receiving aperture each with the same aperture area. To show the net diversity gain of a multiple aperture receiver system, BER performances and outage probabilities of MRC and SC multiple aperture receiver systems are compared with a single monolithic aperture with the same total aperture area (same total average incident optical power) for satellite-to-ground downlink optical communications. All the numerical results are verified by Monte-Carlo simulations. PMID:26368880

  3. COX7A2L Is a Mitochondrial Complex III Binding Protein that Stabilizes the III2+IV Supercomplex without Affecting Respirasome Formation.

    PubMed

    Pérez-Pérez, Rafael; Lobo-Jarne, Teresa; Milenkovic, Dusanka; Mourier, Arnaud; Bratic, Ana; García-Bartolomé, Alberto; Fernández-Vizarra, Erika; Cadenas, Susana; Delmiro, Aitor; García-Consuegra, Inés; Arenas, Joaquín; Martín, Miguel A; Larsson, Nils-Göran; Ugalde, Cristina

    2016-08-30

    Mitochondrial respiratory chain (MRC) complexes I, III, and IV associate into a variety of supramolecular structures known as supercomplexes and respirasomes. While COX7A2L was originally described as a supercomplex-specific factor responsible for the dynamic association of complex IV into these structures to adapt MRC function to metabolic variations, this role has been disputed. Here, we further examine the functional significance of COX7A2L in the structural organization of the mammalian respiratory chain. As in the mouse, human COX7A2L binds primarily to free mitochondrial complex III and, to a minor extent, to complex IV to specifically promote the stabilization of the III2+IV supercomplex without affecting respirasome formation. Furthermore, COX7A2L does not affect the biogenesis, stabilization, and function of the individual oxidative phosphorylation complexes. These data show that independent regulatory mechanisms for the biogenesis and turnover of different MRC supercomplex structures co-exist.

  4. COX7A2L Is a Mitochondrial Complex III Binding Protein that Stabilizes the III2+IV Supercomplex without Affecting Respirasome Formation.

    PubMed

    Pérez-Pérez, Rafael; Lobo-Jarne, Teresa; Milenkovic, Dusanka; Mourier, Arnaud; Bratic, Ana; García-Bartolomé, Alberto; Fernández-Vizarra, Erika; Cadenas, Susana; Delmiro, Aitor; García-Consuegra, Inés; Arenas, Joaquín; Martín, Miguel A; Larsson, Nils-Göran; Ugalde, Cristina

    2016-08-30

    Mitochondrial respiratory chain (MRC) complexes I, III, and IV associate into a variety of supramolecular structures known as supercomplexes and respirasomes. While COX7A2L was originally described as a supercomplex-specific factor responsible for the dynamic association of complex IV into these structures to adapt MRC function to metabolic variations, this role has been disputed. Here, we further examine the functional significance of COX7A2L in the structural organization of the mammalian respiratory chain. As in the mouse, human COX7A2L binds primarily to free mitochondrial complex III and, to a minor extent, to complex IV to specifically promote the stabilization of the III2+IV supercomplex without affecting respirasome formation. Furthermore, COX7A2L does not affect the biogenesis, stabilization, and function of the individual oxidative phosphorylation complexes. These data show that independent regulatory mechanisms for the biogenesis and turnover of different MRC supercomplex structures co-exist. PMID:27545886

  5. Continued DNA synthesis in replication checkpoint mutants leads to fork collapse.

    PubMed

    Sabatinos, Sarah A; Green, Marc D; Forsburg, Susan L

    2012-12-01

    Hydroxyurea (HU) treatment activates the intra-S phase checkpoint proteins Cds1 and Mrc1 to prevent replication fork collapse. We found that prolonged DNA synthesis occurs in cds1Δ and mrc1Δ checkpoint mutants in the presence of HU and continues after release. This is coincident with increased DNA damage measured by phosphorylated histone H2A in whole cells during release. High-resolution live-cell imaging shows that mutants first accumulate extensive replication protein A (RPA) foci, followed by increased Rad52. Both DNA synthesis and RPA accumulation require the MCM helicase. We propose that a replication fork "collapse point" in HU-treated cells describes the point at which accumulated DNA damage and instability at individual forks prevent further replication. After this point, cds1Δ and mrc1Δ forks cannot complete genome replication. These observations establish replication fork collapse as a dynamic process that continues after release from HU block.

  6. Response Simulation of a Micro Reinforced Concrete Target Under Ballistic Impact

    NASA Astrophysics Data System (ADS)

    Mohan, V.; Rajasankar, J.; Iyer, N. R.

    2014-05-01

    The response of concrete structures subjected to impact loading has received extensive attention in both civil and military applications. Research on improving the shock resistance of concrete has led to the development of cementitious composites. Micro Reinforced Concrete (MRC), a type of cementitious composite, is a concrete matrix embedded with multilayered steel wire meshes. This paper presents 3D hydrocode simulations of MRC panels subjected to impact under a ballistic range. A finite element model based on Lagrange formulation is used to represent both a 300 mm × 300 mm × 100 mm target with 30 layers of wire mesh and a 5.56 × 45 mm projectile in simulations. Penetration depth and damage patterns of the MRC mesh cement composite panel are numerically compared with those of the field experiment. The results show a relatively good agreement.

  7. Performance analysis of satellite-to-ground downlink coherent optical communications with spatial diversity over Gamma-Gamma atmospheric turbulence.

    PubMed

    Ma, Jing; Li, Kangning; Tan, Liying; Yu, Siyuan; Cao, Yubin

    2015-09-01

    The performances of satellite-to-ground downlink optical communications over Gamma-Gamma distributed atmospheric turbulence are studied for a coherent detection receiving system with spatial diversity. Maximum ratio combining (MRC) and selection combining (SC) techniques are considered as practical schemes to mitigate the atmospheric turbulence. Bit-error rate (BER) performances for binary phase-shift keying modulated coherent detection and outage probabilities are analyzed and compared for SC diversity using analytical results and for MRC diversity through an approximation method with different numbers of receiving aperture each with the same aperture area. To show the net diversity gain of a multiple aperture receiver system, BER performances and outage probabilities of MRC and SC multiple aperture receiver systems are compared with a single monolithic aperture with the same total aperture area (same total average incident optical power) for satellite-to-ground downlink optical communications. All the numerical results are verified by Monte-Carlo simulations.

  8. Biodiversity of Spongosorites coralliophaga (Stephens, 1915) on coral rubble at two contrasting cold-water coral reef settings

    NASA Astrophysics Data System (ADS)

    Kazanidis, Georgios; Henry, Lea-Anne; Roberts, J. Murray; Witte, Ursula F. M.

    2016-03-01

    Cold-water coral reefs (CWRs) in the northeast Atlantic harbor diverse sponge communities. Knowledge of deep-sea sponge ecology is limited and this leaves us with a fragmented understanding of the ecological roles that sponges play in CWR ecosystems. We present the first study of faunal biodiversity associated with the massive demosponge Spongosorites coralliophaga (Stephens, 1915) that typically colonizes coral debris fields of CWRs. Our study focused on the sessile fauna inhabiting sponges mixed with coral rubble at two contrasting settings in the northeast Atlantic: the shallow inshore (120-190 m water depth) Mingulay Reef Complex (MRC) and the deep offshore (500-1200 m) Logachev Mound (LM) coral province. MRC is dominated by the scleractinian Lophelia pertusa, while LM is dominated by L. pertusa and Madrepora oculata. Nine sponge-coral rubble associations were collected from MRC and four from LM. Measurements of abundance, species richness, diversity, evenness, dry biomass, and composition of sessile fauna on sponge and coral rubble microhabitats were undertaken. Differences in community composition between the two regions were mainly a response to changes in fauna with depth. Fauna composition was also different between sponge and coral rubble within each region. Infauna constituted a minor component of the sponge-associated fauna in MRC but had a higher contribution in LM. Sponge and coral rubble sessile fauna in both regions was mainly composed of cnidarians and molluscs, similarly to some previous studies. Sponges' outer surfaces at MRC were colonized by a species-rich community with high abundance and biomass suggesting that S. coralliophaga at MRC acts as a settlement surface for various organisms but such a role is not the case at LM. This difference in the role of S. coralliophaga as a biological structure is probably related to differences in fauna composition with depth, bottom current speed, and the quantity/quality of food supplied to the benthos.

  9. Genistein mediates the selective radiosensitizing effect in NSCLC A549 cells via inhibiting methylation of the keap1 gene promoter region

    PubMed Central

    Liu, Xiongxiong; Sun, Chao; Liu, Bingtao; Jin, Xiaodong; Li, Ping; Zheng, Xiaogang; Zhao, Ting; Li, Feifei; Li, Qiang

    2016-01-01

    Non-small cell lung cancer (NSCLC) cells often possess a hypermethylated Keap1 promoter, which decreases Keap1 mRNA and protein expression levels, thus impairing the Nrf2-Keap1 pathway and thereby leading to chemo- or radio-resistance. In this study, we showed that genistein selectively exhibited a radiosensitizing effect on NSCLC A549 cells but not on normal lung fibroblast MRC-5 cells. Genistein caused oxidative stress in A549 cells rather than MRC-5 cells, as determined by the oxidation of the ROS-sensitive probe DCFH-DA and oxidative damage marked by MDA, PCO or 8-OHdG content. In A549 instead of MRC-5 cells, genistein reduced the level of methylation in the Keap1 promoter region, leading to an increased mRNA expression, thus effectively inhibited the transcription of Nrf2 to the nucleus, which suppressed the Nrf2-dependent antioxidant and resulted in the upregulation of ROS. Importantly, when combined with radiation, genistein further increased the ROS levels in A549 cells whereas decreasing the radiation-induced oxidative stress in MRC-5 cells, possibly via increasing the expression levels of Nrf2, GSH and HO-1. Moreover, radiation combined with genistein significantly increased cell apoptosis in A549 but not MRC-5 cells. Together, the results herein show that the intrinsic difference in the redox status of A549 and MRC-5 cells could be the target for genistein to selectively sensitize A549 cells to radiation, thereby leading to an increase in radiosensitivity for A549 cells. PMID:27029077

  10. Hydrogen sulfide suppresses migration, proliferation and myofibroblast transdifferentiation of human lung fibroblasts.

    PubMed

    Fang, Li-Ping; Lin, Qing; Tang, Chao-Shu; Liu, Xin-Min

    2009-12-01

    We previously reported that hydrogen sulfide (H(2)S) was implicated in the pathogenesis of bleomycin-induced pulmonary fibrosis in rat, but the cellular mechanisms underlying the role it played were not well characterized. The present study was undertaken to investigate the role of the exogenous H(2)S in human lung fibroblast (MRC5) migration, proliferation and myofibroblast transdifferentiation induced by fetal bovine serum (FBS) and growth factors in vitro, to elucidate the mechanisms by which H(2)S inhibits pathogenesis of pulmonary fibrosis. We found that H(2)S incubation significantly decreased the MRC5 cell migration distance stimulated by FBS and basic fibroblast growth factor (bFGF), inhibited MRC5 cell proliferation induced by FBS and platelet-derived growth factor-BB (PDGF-BB), and also inhibited transforming growth factor-beta1 (TGF-beta1) induced MRC5 cell transdifferentiation into myofibroblasts. Moreover, preincubation with H(2)S decreased extracellular signal-regulated kinase (ERK1/2) phosphorylation in MRC5 cells induced by FBS, PDGF-BB, TGF-beta1, and bFGF. However, the inhibition effects of H(2)S on MRC5 cell migration, proliferation and myofibroblast transdifferentiation were not attenuated by glibenclamide, an ATP-sensitive K(+) channel (K(ATP)) blocker. Thus, H(2)S directly suppressed fibroblast migration, proliferation and phenotype transform stimulated by FBS and growth factors in vitro, which suggests that it could be an important mechanism of H(2)S-suppressed pulmonary fibrosis. These effects of H(2)S on pulmonary fibroblasts were, at least in part, mediated by decreased ERK phosphorylation and were not dependent on K(ATP) channel opening.

  11. Why the Medical Research Council refused Robert Edwards and Patrick Steptoe support for research on human conception in 1971

    PubMed Central

    Johnson, Martin H.; Franklin, Sarah B.; Cottingham, Matthew; Hopwood, Nick

    2010-01-01

    BACKGROUND In 1971, Cambridge physiologist Robert Edwards and Oldham gynaecologist Patrick Steptoe applied to the UK Medical Research Council (MRC) for long-term support for a programme of scientific and clinical ‘Studies on Human Reproduction’. The MRC, then the major British funder of medical research, declined support on ethical grounds and maintained this policy throughout the 1970s. The work continued with private money, leading to the birth of Louise Brown in 1978 and transforming research in obstetrics, gynaecology and human embryology. METHODS The MRC decision has been criticized, but the processes by which it was reached have yet to be explored. Here, we present an archive-based analysis of the MRC decision. RESULTS We find evidence of initial support for Edwards and Steptoe, including from within the MRC, which invited the applicants to join its new directly funded Clinical Research Centre at Northwick Park Hospital. They declined the offer, preferring long-term grant support at the University of Cambridge, and so exposed the project to competitive funding mode. Referees and the Clinical Research Board saw the institutional set-up in Cambridge as problematic with respect to clinical facilities and patient management; gave infertility a low priority compared with population control; assessed interventions as purely experimental rather than potential treatments, and so set the bar for safety high; feared fatal abnormalities and so wanted primate experiments first; and were antagonized by the applicants’ high media profile. The rejection set MRC policy on IVF for 8 years, until, after the birth of just two healthy babies, the Council rapidly converted to enthusiastic support. CONCLUSIONS This analysis enriches our view of a crucial decision, highlights institutional opportunities and constraints and provides insight into the then dominant attitudes of reproductive scientists and clinicians towards human conception research. PMID:20657027

  12. The Impact of Gd-Eob-Dtpa-Enhanced MR Cholangiography in Biliary Diseases: Comparison with T2-Weighted MR Cholangiopancreatography

    PubMed Central

    Özmen, Evrim; Algın, Oktay; Evrimler, Şehnaz; Arslan, Halil

    2016-01-01

    Background: Contrast enhanced magnetic resonance cholangiography is a novel technique and promising method in demonstrating biliary tree anatomy and evaluating biliary disorders. However, to date, there are a limited number of studies that have focused on the impact of this technique. Aims: We aimed to evaluate the additional role of contrast enhanced MR cholangiography (MRC) and compare contrast enhanced MRC with T2-weighted (w) magnetic resonance cholangiopancreatography (MRCP) in the diagnosis of biliary disorders. Study Design: Diagnostic accuracy study. Methods: The T2w-MRCP and contrast enhanced MRC sequences of 31 patients whose gold standard test results were available were scored visually for the existence of pathological findings with regard to any of the biliary diseases. Gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) was used as the contrast agent. The correlation values were determined according to the statistical analysis made from those scores and the sensitivity, specificity and accuracy values of each sequence were detected as well. Results: We detected that the correlation values with gold standard methods of contrast enhanced MRC sequences were significantly higher than the ones of T2w-MRCP sequences. The correlation ratios of T2w-MRCP sequences were between 26 and 34%, while those for contrast enhanced MRC sequences were between 81 and 83% for the first reader and the correlation ratios of T2w-MRCP sequences were between 10 and 61%, whereas those of contrast enhanced MRC were between 79 and 81% for the second reader The mean sensitivity, specificity and accuracy values of T2w-MRCP sequences were 14.3–42.5%, 85–89.2% and 59.3–72.5%, respectively, while the mean sensitivity, specificity and accuracy values of contrast enhanced MRC sequences were 100%, 86.7% and 93.2–93.3%, respectively. Conclusion: We suggest that obtaining of contrast enhanced MRC sequences in addition to the T2w-MRCP can be useful in the

  13. Adaptation of hepatitis A virus to high titre growth in diploid and permanent cell cultures.

    PubMed

    Gregersen, J P; Mehdi, S; Mauler, R

    1988-01-01

    A hepatitis A virus isolate originally obtained from the feces of a clinically ill patient and passaged in diploid human embryonic kidney and lung cells was adapted to grow in MRC-5, Cercopithecus aethiops muscle and in Vero cells. Three different adaptation methods were applied. Either method proved to be suitable to finally give high virus titres of cell-bound as well as cell-free virus in the supernatant of infected cultures during 10 to 15 passages. An easily performable immunoperoxidase staining method was used for the titration of hepatitis A virus in microtitre plates. Cytopathogenic changes in MRC-5 cell cultures infected with fully adapted virus are described.

  14. Data on cell viability of human lung fibroblasts treated with polyphenols-rich extract from Plinia trunciflora (O. Berg) Kausel).

    PubMed

    Calloni, Caroline; Silva Santos, Luciana Fernandes; Martínez, Luana Soares; Salvador, Mirian

    2016-03-01

    Jaboticaba (Plinia trunciflora (O. Berg) Kausel) is a Brazilian native berry, which presents high levels of polyphenols. Here we provide data related to the effects of the polyphenols-rich extract from jaboticaba on the cell viability, mitochondrial complex I (nicotinamide adenine dinucleotide/CoQ oxidoreductase) activity and ATP biosynthesis of human lung fibroblast cells (MRC-5) treated with amiodarone. The data presented in this article demonstrate that the polyphenols-rich extract from jaboticaba was able to reduce cell death as well as the decrease in complex I activity and ATP biosynthesis caused by amiodarone in MRC-5 cells.

  15. Data on cell viability of human lung fibroblasts treated with polyphenols-rich extract from Plinia trunciflora (O. Berg) Kausel)

    PubMed Central

    Calloni, Caroline; Silva Santos, Luciana Fernandes; Martínez, Luana Soares; Salvador, Mirian

    2016-01-01

    Jaboticaba (Plinia trunciflora (O. Berg) Kausel) is a Brazilian native berry, which presents high levels of polyphenols. Here we provide data related to the effects of the polyphenols-rich extract from jaboticaba on the cell viability, mitochondrial complex I (nicotinamide adenine dinucleotide/CoQ oxidoreductase) activity and ATP biosynthesis of human lung fibroblast cells (MRC-5) treated with amiodarone. The data presented in this article demonstrate that the polyphenols-rich extract from jaboticaba was able to reduce cell death as well as the decrease in complex I activity and ATP biosynthesis caused by amiodarone in MRC-5 cells. PMID:26870757

  16. Driving a Semiautonomous Mobile Robotic Car Controlled by an SSVEP-Based BCI

    PubMed Central

    2016-01-01

    Brain-computer interfaces represent a range of acknowledged technologies that translate brain activity into computer commands. The aim of our research is to develop and evaluate a BCI control application for certain assistive technologies that can be used for remote telepresence or remote driving. The communication channel to the target device is based on the steady-state visual evoked potentials. In order to test the control application, a mobile robotic car (MRC) was introduced and a four-class BCI graphical user interface (with live video feedback and stimulation boxes on the same screen) for piloting the MRC was designed. For the purpose of evaluating a potential real-life scenario for such assistive technology, we present a study where 61 subjects steered the MRC through a predetermined route. All 61 subjects were able to control the MRC and finish the experiment (mean time 207.08 s, SD 50.25) with a mean (SD) accuracy and ITR of 93.03% (5.73) and 14.07 bits/min (4.44), respectively. The results show that our proposed SSVEP-based BCI control application is suitable for mobile robots with a shared-control approach. We also did not observe any negative influence of the simultaneous live video feedback and SSVEP stimulation on the performance of the BCI system. PMID:27528864

  17. Motor unit number estimation as a complementary test to routine electromyography in the diagnosis of amyotrophic lateral sclerosis.

    PubMed

    Gawel, Malgorzata; Zalewska, Ewa; Lipowska, Marta; Kostera-Pruszczyk, Anna; Szmidt-Salkowska, Elzbieta; Kaminska, Anna

    2016-02-01

    Electromyographic (EMG) abnormalities that reveal denervation and reinnervation caused by lower motor neuron degeneration do not reflect the number of motor units that determines muscle strength. Consequently, motor unit activity potential (MUAP) parameters do not reflect muscle dysfunction. The aim of the study was to compare the value of motor unit number estimation (MUNE) and MUAP parameters as indicators of clinical muscle dysfunction in patients with amyotrophic lateral sclerosis (ALS), and to analyze the role of MUNE as a supplement to the EMG criteria for the diagnosis of ALS. In 25 patients with ALS, MUNE by the multipoint incremental method in the abductor digiti minimi (ADM) and quantitative EMG in the first dorsal interosseous (FDI) were obtained. The Medical Research Council (MRC) scale was used to evaluate clinical muscle dysfunction. A strong correlation between the number of motor units evaluated by MUNE and ADM clinical function by the MRC scale was found (P<0.001). An increased value of surface-detected single motor action potential was associated with a decreased MRC score for ADM (P<0.1). No relation was found between MUAP parameters in FDI and MRC scores. Our data support the value of the MUNE method for the detection of motor unit loss in ALS, and it could be postulated that MUNE studies may be considered complementary tests for ALS in a future revision of ALS criteria.

  18. Comparing the magnetic resonant coupling radiofrequency stimulation to the traditional approaches: Ex-vivo tissue voltage measurement and electromagnetic simulation analysis

    SciTech Connect

    Yeung, Sai Ho; Pradhan, Raunaq; Feng, Xiaohua; Zheng, Yuanjin

    2015-09-15

    Recently, the design concept of magnetic resonant coupling has been adapted to electromagnetic therapy applications such as non-invasive radiofrequency (RF) stimulation. This technique can significantly increase the electric field radiated from the magnetic coil at the stimulation target, and hence enhancing the current flowing through the nerve, thus enabling stimulation. In this paper, the developed magnetic resonant coupling (MRC) stimulation, magnetic stimulation (MS) and transcutaneous electrical nerve stimulation (TENS) are compared. The differences between the MRC RF stimulation and other techniques are presented in terms of the operating mechanism, ex-vivo tissue voltage measurement and electromagnetic simulation analysis. The ev-vivo tissue voltage measurement experiment is performed on the compared devices based on measuring the voltage induced by electromagnetic induction at the tissue. The focusing effect, E field and voltage induced across the tissue, and the attenuation due to the increase of separation between the coil and the target are analyzed. The electromagnetic stimulation will also be performed to obtain the electric field and magnetic field distribution around the biological medium. The electric field intensity is proportional to the induced current and the magnetic field is corresponding to the electromagnetic induction across the biological medium. The comparison between the MRC RF stimulator and the MS and TENS devices revealed that the MRC RF stimulator has several advantages over the others for the applications of inducing current in the biological medium for stimulation purposes.

  19. Hydrologic evaluation of the lower Mekong River Basin with the Soil and Water Assessment Tool model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Recently the Mekong River Commission (MRC) has developed a computer package so-called Decision Support Framework (DSF) under the Water Utilization Programme (WUP). The development was aimed to implement the 1995 Agreement on the Water Utilization with sustainable development and equitable manner of ...

  20. Caffeic acid attenuates rat liver reperfusion injury through sirtuin 3-dependent regulation of mitochondrial respiratory chain.

    PubMed

    Mu, Hong-Na; Li, Quan; Pan, Chun-Shui; Liu, Yu-Ying; Yan, Li; Hu, Bai-He; Sun, Kai; Chang, Xin; Zhao, Xin-Rong; Fan, Jing-Yu; Han, Jing-Yan

    2015-08-01

    Sirtuin 3 (Sirt3) plays critical roles in regulating mitochondrial oxidative metabolism. However, whether Sirt3 is involved in liver ischemia and reperfusion (I/R) injury remains elusive. Caffeic acid (CA) is a natural antioxidant derived from Salvia miltiorrhiza. Whether CA protects against liver I/R injury through regulating Sirt3 and the mitochondrial respiratory chain (MRC) is unclear. This study investigated the effect of CA on liver I/R injury, microcirculatory disturbance, and potential mechanisms, particularly focusing on Sirt3-dependent MRC. Liver I/R of male Sprague-Dawley rats was established by occlusion of portal area vessels for 30 min followed by 120 min of reperfusion. CA (15 mg/kg/h) was continuously infused via the femoral vein starting 30 min before ischemia. After I/R, Sirt3 expression, and MRC activity decreased, acetylation of NADH dehydrogenase [ubiquinone] 1 alpha subcomplex subunit 9 and succinate dehydrogenase complex, subunit A, flavoprotein variant provoked, and the liver microcirculatory disturbance and injury were observed. Treatment with CA attenuated liver injury, inhibited Sirt3 down-expression, and up-regulated MRC activity. CA attenuated rat liver microcirculatory disturbance and oxidative injury through regulation of Sirt3 and the mitochondrial respiratory chain. PMID:25960048

  1. Two Simulated-Smog Atmospheres with Different Chemical Compositions Produce Contrasting Mutagenicity in Salmonella**

    EPA Science Inventory

    Ozone (O3), particulate matter (PM), and nitrogen dioxide (NO2) are criteria pollutants used to evaluate air quality. Using EPA’s Mobile Reaction Chamber (MRC), we generated 2 simulated-smog atmospheres (SSA-1 & SSA-2) with different concentrations of these criteria pol...

  2. Stuart Gatehouse: A Personal Appreciation

    PubMed Central

    Haggard, Mark

    2008-01-01

    Stuart Gatehouse worked in the MRC Institute of Hearing Research Scottish Section for 29 years until his untimely death in 2007. The former director records a personal appreciation but also an explanation, for those who did not know him well, of the mixture of qualities that made him an outstanding applied scientist. PMID:18567588

  3. Red blood cell parameters in antenatal nonsickling hemoglobinopathy screening

    PubMed Central

    Bencaiova, Gabriela; Dapoto, Kristina; Zimmermann, Roland; Krafft, Alexander

    2015-01-01

    Objective To find a hematological parameter and the cut-off level for identification of nonsickling hemoglobinopathies in pregnant women. Materials and methods Venous blood samples of 849 women with singleton pregnancies were collected at the first visit. All women who met inclusion criteria were examined for nonsickling hemoglobinopathy. On the basis of the sensitivity and the specificity of different cut-off levels for hematological parameters, we calculated the optimal clinically practicable parameter for screening of nonsickling hemoglobinopathies in pregnant women. Results On the basis of the sensitivity and the specificity, the best screening parameters for the identification of nonsickling hemoglobinopathies among nonanemic pregnant women are mean corpuscular volume (MCV) with cut-off ≤80 fL (Youden’s index 91.2%), mean corpuscular hemoglobin (MCH) <27.5 pg (Youden’s index 90.7%), and microcytosis (MRC) ≥3% (Youden’s index 90.2%). An analysis using receiver operating characteristic curves and the calculated Youden’s index showed that MCV ≤76 fL, MCH ≤24 pg, or MRC ≥10% are the best red blood cell indices for the screening of nonsickling hemoglobinopathy among anemic women with iron deficiency. Conclusion Our results suggest targeted screening for nonsickling hemoglobinopathies in nonanemic pregnant women with MCV ≤80 fL, MCH ≤27.5 pg, or MRC ≥3% and in anemic women with MCV ≤76 fL, MCH ≤24 pg, or MRC ≥10%. PMID:25914560

  4. Coexpression within Integrated Mitochondrial Pathways Reveals Different Networks in Normal and Chemically Treated Transcriptomes

    PubMed Central

    Chen, Cong; Hyun, Tae Kyung; Han, Xiao; Feng, Zhihui; Li, Yuan; Liu, Xiaolong; Liu, Jiankang

    2014-01-01

    As energy producers, mitochondria play a pivotal role in multiple cellular processes. Although several lines of evidence suggest that differential expression of mitochondrial respiratory complexes (MRCs) has a significant impact on mitochondrial function, the role of integrated MRCs in the whole coexpression network has yet to be revealed. In this study, we construct coexpression networks based on microarray datasets from different tissues and chemical treatments to explore the role of integrated MRCs in the coexpression network and the effects of different chemicals on the mitochondrial network. By grouping MRCs as one seed target, the hypergeometric distribution allowed us to identify genes that are significantly coexpress with whole MRCs. Coexpression among 46 MRC genes (approximately 78% of MRC genes tested) was significant in the normal tissue transcriptome dataset. These MRC genes are coexpressed with genes involved in the categories “muscle system process,” “metabolic process,” and “neurodegenerative disease pathways,” whereas, in the chemically treated tissues, coexpression of these genes mostly disappeared. These results indicate that chemical stimuli alter the normal coexpression network of MRC genes. Taken together, the datasets obtained from the different coexpression networks are informative about mitochondrial biogenesis and should contribute to understanding the side effects of drugs on mitochondrial function. PMID:25089262

  5. Anti-infective mannose receptor immune mechanism in large yellow croaker (Larimichthys crocea).

    PubMed

    Dong, Xiangli; Li, Jiji; He, Jianyu; Liu, Wei; Jiang, Lihua; Ye, Yingying; Wu, Changwen

    2016-07-01

    Mannose receptor (MR) is a pattern recognition receptor (PRR) that plays a significant role in immunity responses. Its role has been described extensively in mammals, but very rarely in fish. Recently, with the rapid development of an aquaculture industry cultivating large yellow croaker (Larimichthys crocea), infectious diseases caused by viruses, bacteria and parasites are becoming more frequent and more severe, in particular bacterial infections caused by Vibrio anguillarum, resulting in great economical losses. Extensive use of antibiotics as conventional treatment has led to microenvironment imbalances, development of drug-resistant bacteria and deposition of drug residues, which cause environmental pollution and ultimately affect human health. The purpose of this pilot study was to detect the transcriptional levels of C-type mannose receptor genes MRC1 (4710-bp ORF; encoding 1437 aa; a signal peptide, a SMART RICIN domain, a SMART FN2 domain, eight SMART CLECT domain, and a transmembrane helix region) and MRC2 (3996-bp ORF; encoding 1484 aa; a SMART FN2 domain, eight SMART CLECT domains, and a transmembrane region) in the liver, kidney and spleen tissues of L. crocea challenged by V. anguillarum, to explore the effective domain and the molecular response mechanisms of MRC1 and MRC2, and, ultimately, to explore the possibility of developing a vaccine targeting V. anguillarum infections.

  6. The Medical Reserve Corps as part of the federal medical and public health response in disaster settings.

    PubMed

    Frasca, Dominic R

    2010-09-01

    The Secretary of the Department of Health and Human Services (HHS), through the Office of the Assistant Secretary for Preparedness and Response (ASPR), coordinates federal Emergency Support Function (ESF) #8 preparedness, response, and recovery actions. To address these needs, the ASPR can draw on trained personnel from a variety of sources, both from within and outside HHS. Among the resources under the domain of HHS is the Medical Reserve Corps (MRC), directed by the Office of the Civilian Volunteer Medical Reserve Corps (OCVMRC) in the Office of the Surgeon General. MRC units are community based and function as a way to locally organize and utilize medical and public health professionals, such as physicians, nurses, pharmacists, dentists, veterinarians, and epidemiologists. Nonclinical volunteers, such as interpreters, chaplains, office workers, legal advisors, and others, can fill logistical and support roles in MRC units. This article discusses locally controlled (Hurricanes Gustav and Ike) and federalized (Hurricanes Katrina and Rita) MRC activations, and it describes the advantages of using medical volunteers in a large-scale disaster response setting.

  7. [Fusion imaging of 3D MR cisternography/angiography for differential diagnosis of internal carotid-posterior communicating artery aneurysms and infundibular dilations].

    PubMed

    Satoh, Toru; Sasahara, Wataru; Omi, Megumi; Ohsako, Chika

    2006-05-01

    By using a fusion imaging of three-dimensional (3D) magnetic resonance cisternography (MRC) and coregistered magnetic resonance angiography (MRA), protrusions at the bifurcation of the internal carotid-posterior communication artery, detected by MRA, were investigated to differentiate between the infundibular dilations and aneurysms. The MRA, obtained by the 3D time-of-flight sequence, showed the flow-related arterial structures by means of an inflow effect mainly induced by the peak systolic flow velocity. The MRC, obtained by 3D fast spin-echo sequence, depicted the contours of the vascular structures within the cisternal space in contrast to the surrounding cerebrospinal fluid. Fusion images of 3D MRC/MRA showed the anatomy of protrusions from the different viewpoints with flow-related intraluminal images (MRA) in conjunction with outer-wall configuration images of the vascular structures (MRC). This imaging technique may be useful to differentiate the infundibular dilations from the internal carotid-posterior communicating artery aneurysms.

  8. The Diagnosis and Management of Auditory Processing Disorder

    ERIC Educational Resources Information Center

    Moore, David R.

    2011-01-01

    Purpose: To provide a personal perspective on auditory processing disorder (APD), with reference to the recent clinical forum on APD and the needs of clinical speech-language pathologists and audiologists. Method: The Medical Research Council-Institute of Hearing Research (MRC-IHR) has been engaged in research into APD and auditory learning for 8…

  9. Driving a Semiautonomous Mobile Robotic Car Controlled by an SSVEP-Based BCI.

    PubMed

    Stawicki, Piotr; Gembler, Felix; Volosyak, Ivan

    2016-01-01

    Brain-computer interfaces represent a range of acknowledged technologies that translate brain activity into computer commands. The aim of our research is to develop and evaluate a BCI control application for certain assistive technologies that can be used for remote telepresence or remote driving. The communication channel to the target device is based on the steady-state visual evoked potentials. In order to test the control application, a mobile robotic car (MRC) was introduced and a four-class BCI graphical user interface (with live video feedback and stimulation boxes on the same screen) for piloting the MRC was designed. For the purpose of evaluating a potential real-life scenario for such assistive technology, we present a study where 61 subjects steered the MRC through a predetermined route. All 61 subjects were able to control the MRC and finish the experiment (mean time 207.08 s, SD 50.25) with a mean (SD) accuracy and ITR of 93.03% (5.73) and 14.07 bits/min (4.44), respectively. The results show that our proposed SSVEP-based BCI control application is suitable for mobile robots with a shared-control approach. We also did not observe any negative influence of the simultaneous live video feedback and SSVEP stimulation on the performance of the BCI system.

  10. Mental health research, ethics and multiculturalism.

    PubMed

    Bailes, Marion J; Minas, I Harry; Klimidis, Steven

    2006-01-01

    In this paper we examine ethical issues relevant to conducting mental health research with refugees and immigrant communities that have cultural orientations and social organisation that are substantially different to those of the broader Australian community, and we relate these issues to NH&MRC Guidelines. We describe the development and conduct of a mental health research project carried out recently in Melbourne with the Somali community, focusing on ethical principles involved, and relating these to the NH&MRC National Statement on Ethical Conduct in Research Involving Humans, and the NH&MRC document Values and Ethics: Guidelines for Ethical Conduct in Aboriginal and Torres Strait Islander Health Research. The experience of conducting mental health research with the Somali community highlights the fact that the principles of inclusion and benefit enunciated in the NH&MRC document Values and Ethics are particularly pertinent when conducting research with refugees and immigrant communities that are culturally distant to those of the broader Australian community. These principles inform issues of research design and consent, as well as guiding respectful engagement with the participating community and communication of the research findings.

  11. Strategy optimization for mask rule check in wafer fab

    NASA Astrophysics Data System (ADS)

    Yang, Chuen Huei; Lin, Shaina; Lin, Roger; Wang, Alice; Lee, Rachel; Deng, Erwin

    2015-07-01

    Photolithography process is getting more and more sophisticated for wafer production following Moore's law. Therefore, for wafer fab, consolidated and close cooperation with mask house is a key to achieve silicon wafer success. However, generally speaking, it is not easy to preserve such partnership because many engineering efforts and frequent communication are indispensable. The inattentive connection is obvious in mask rule check (MRC). Mask houses will do their own MRC at job deck stage, but the checking is only for identification of mask process limitation including writing, etching, inspection, metrology, etc. No further checking in terms of wafer process concerned mask data errors will be implemented after data files of whole mask are composed in mask house. There are still many potential data errors even post-OPC verification has been done for main circuits. What mentioned here are the kinds of errors which will only occur as main circuits combined with frame and dummy patterns to form whole reticle. Therefore, strategy optimization is on-going in UMC to evaluate MRC especially for wafer fab concerned errors. The prerequisite is that no impact on mask delivery cycle time even adding this extra checking. A full-mask checking based on job deck in gds or oasis format is necessary in order to secure acceptable run time. Form of the summarized error report generated by this checking is also crucial because user friendly interface will shorten engineers' judgment time to release mask for writing. This paper will survey the key factors of MRC in wafer fab.

  12. Magnetite nanoparticles induced adaptive mechanisms counteract cell death in human pulmonary fibroblasts.

    PubMed

    Radu, Mihaela; Dinu, Diana; Sima, Cornelia; Burlacu, Radu; Hermenean, Anca; Ardelean, Aurel; Dinischiotu, Anca

    2015-10-01

    Magnetite nanoparticles (MNP) have attracted great interest for biomedical applications due to their unique chemical and physical properties, but the MNP impact on human health is not fully known. Consequently, our study proposes to highlight the biochemical mechanisms that underline the toxic effects of MNP on a human lung fibroblast cell line (MRC-5). The cytotoxicity generated by MNP in MRC-5 cells was dose and time-dependent. MNP-treated MRC-5 cells accumulated large amount of iron and reactive oxygen species (ROS) and exhibited elevated antioxidant scavenger enzymes. Reduced glutathione (GSH) depletion and enhanced lipid peroxidation (LPO) processes were also observed. The cellular capacity to counteract the oxidative damage was sustained by high levels of heat shock protein 60 (Hsp60), a protein that confers resistance against ROS attack and inhibition of cell death. While significant augmentations in nitric oxide (NO) and prostaglandine E2 (PGE2) levels were detected after 72 h of MNP-exposure only, caspase-1 was activated earlier starting with 24h post-treatment. Taken together, our results suggest that MRC-5 cells have the capacity to develop cell protection mechanisms against MNP. Detailed knowledge of the mechanisms induced by MNP in cell culture could be essential for their prospective use in various in vivo biochemical applications. PMID:26065626

  13. The Effects of Level of Counselor Education on Client Outcomes in the Public Vocational Rehabilitation System of New Jersey

    ERIC Educational Resources Information Center

    Rehabilitation Research, Policy, and Education, 2013

    2013-01-01

    To fulfill the goal of having counselors qualified through the Comprehensive System of Personnel Development (CSPD), the Division of Vocational Rehabilitation Services in New Jersey (DVRS-NJ) committed to have selected counselors attend a Master's Degree in Rehabilitation Counseling (MRC) graduate program. This study examines 14…

  14. Effects of a Preschool Intervention on Cognitive Development among East-African Preschool Children: A Flexibly Time-Coded Growth Model

    ERIC Educational Resources Information Center

    Malmberg, Lars-Erik; Mwaura, Peter; Sylva, Kathy

    2011-01-01

    The aim of the study is to investigate the effects of the Madrasa Resource Center (MRC), a child-centered intervention program, on East-African (Kenya, Zanzibar, and Uganda) preschool children's cognitive development. Altogether 321 children (153 non-intervention and 168 intervention) participated in a cross-sequential study over three time-points…

  15. Mound calorimetry for explosive surveillance

    SciTech Connect

    Shockey, G.C.; Rodenburg, W.W.

    1985-01-01

    Heat of reaction determinations of pyrotechnics and explosives is made at MRC-Mound by bomb calorimetry. Energy releases from ten calories to 94 kilocalories have been measured accurately using four different calorimeter systems. Each system is described and some heat of reaction results are given. 3 figs., 4 tabs.

  16. A role for p53 in selenium-induced senescence

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The tumor suppressor p53 and the ataxia-telangiectasia mutated (ATM) kinase play important roles in the senescence response to oncogene activation and DNA damage. We have previously shown that selenium-containing compounds can activate an ATM-dependent senescence response in MRC-5 normal fibroblasts...

  17. Anti-infective mannose receptor immune mechanism in large yellow croaker (Larimichthys crocea).

    PubMed

    Dong, Xiangli; Li, Jiji; He, Jianyu; Liu, Wei; Jiang, Lihua; Ye, Yingying; Wu, Changwen

    2016-07-01

    Mannose receptor (MR) is a pattern recognition receptor (PRR) that plays a significant role in immunity responses. Its role has been described extensively in mammals, but very rarely in fish. Recently, with the rapid development of an aquaculture industry cultivating large yellow croaker (Larimichthys crocea), infectious diseases caused by viruses, bacteria and parasites are becoming more frequent and more severe, in particular bacterial infections caused by Vibrio anguillarum, resulting in great economical losses. Extensive use of antibiotics as conventional treatment has led to microenvironment imbalances, development of drug-resistant bacteria and deposition of drug residues, which cause environmental pollution and ultimately affect human health. The purpose of this pilot study was to detect the transcriptional levels of C-type mannose receptor genes MRC1 (4710-bp ORF; encoding 1437 aa; a signal peptide, a SMART RICIN domain, a SMART FN2 domain, eight SMART CLECT domain, and a transmembrane helix region) and MRC2 (3996-bp ORF; encoding 1484 aa; a SMART FN2 domain, eight SMART CLECT domains, and a transmembrane region) in the liver, kidney and spleen tissues of L. crocea challenged by V. anguillarum, to explore the effective domain and the molecular response mechanisms of MRC1 and MRC2, and, ultimately, to explore the possibility of developing a vaccine targeting V. anguillarum infections. PMID:27071518

  18. Comparing the magnetic resonant coupling radiofrequency stimulation to the traditional approaches: Ex-vivo tissue voltage measurement and electromagnetic simulation analysis

    NASA Astrophysics Data System (ADS)

    Yeung, Sai Ho; Pradhan, Raunaq; Feng, Xiaohua; Zheng, Yuanjin

    2015-09-01

    Recently, the design concept of magnetic resonant coupling has been adapted to electromagnetic therapy applications such as non-invasive radiofrequency (RF) stimulation. This technique can significantly increase the electric field radiated from the magnetic coil at the stimulation target, and hence enhancing the current flowing through the nerve, thus enabling stimulation. In this paper, the developed magnetic resonant coupling (MRC) stimulation, magnetic stimulation (MS) and transcutaneous electrical nerve stimulation (TENS) are compared. The differences between the MRC RF stimulation and other techniques are presented in terms of the operating mechanism, ex-vivo tissue voltage measurement and electromagnetic simulation analysis. The ev-vivo tissue voltage measurement experiment is performed on the compared devices based on measuring the voltage induced by electromagnetic induction at the tissue. The focusing effect, E field and voltage induced across the tissue, and the attenuation due to the increase of separation between the coil and the target are analyzed. The electromagnetic stimulation will also be performed to obtain the electric field and magnetic field distribution around the biological medium. The electric field intensity is proportional to the induced current and the magnetic field is corresponding to the electromagnetic induction across the biological medium. The comparison between the MRC RF stimulator and the MS and TENS devices revealed that the MRC RF stimulator has several advantages over the others for the applications of inducing current in the biological medium for stimulation purposes.

  19. Tumorigenicity Evaluation of Umbilical Cord Blood-derived Mesenchymal Stem Cells.

    PubMed

    Park, Sang-Jin; Kim, Hyun-Jung; Kim, Woojin; Kim, Ok-Sun; Lee, Sunyeong; Han, Su-Yeon; Jeong, Eun Ju; Park, Hyun-Shin; Kim, Hea-Won; Moon, Kyoung-Sik

    2016-07-01

    Mesenchymal stem cells (MSCs) have been identified in multiple types of tissue and exhibit characteristic self-renewal and multi-lineage differentiation abilities. However, the possibility of oncogenic transformation after transplantation is concerning. In this study, we investigated the tumorigenic potential of umbilical cord blood-derived MSCs (hUCB-MSCs) relative to MRC-5 and HeLa cells (negative and positive controls, respectively) both in vitro and in vivo. To evaluate tumorigenicity in vitro, anchorage-independent growth was assessed using the soft agar colony formation assay. hUCB-MSCs and MRC-5 cells formed few colonies, while HeLa cells formed a greater number of larger colonies, indicating that hUCB-MSCs and MRC-5 cells do not have anchorage-independent proliferation potential. To detect tumorigenicity in vivo, hUCB-MSCs were implanted as a single subcutaneous injection into BALB/c-nu mice. No tumor formation was observed in mice transplanted with hUCB-MSCs or MRC-5 cells based on macroand microscopic examinations; however, all mice transplanted with HeLa cells developed tumors that stained positive for a human gene according to immunohistochemical analysis. In conclusion, hUCB-MSCs do not exhibit tumorigenic potential based on in vitro and in vivo assays under our experimental conditions, providing further evidence of their safety for clinical applications.

  20. Visualization of heterogeneity and regional grading of gliomas by multiple features using magnetic resonance-based clustered images

    PubMed Central

    Inano, Rika; Oishi, Naoya; Kunieda, Takeharu; Arakawa, Yoshiki; Kikuchi, Takayuki; Fukuyama, Hidenao; Miyamoto, Susumu

    2016-01-01

    Preoperative glioma grading is important for therapeutic strategies and influences prognosis. Intratumoral heterogeneity can cause an underestimation of grading because of the sampling error in biopsies. We developed a voxel-based unsupervised clustering method with multiple magnetic resonance imaging (MRI)-derived features using a self-organizing map followed by K-means. This method produced novel magnetic resonance-based clustered images (MRcIs) that enabled the visualization of glioma grades in 36 patients. The 12-class MRcIs revealed the highest classification performance for the prediction of glioma grading (area under the receiver operating characteristic curve = 0.928; 95% confidential interval = 0.920–0.936). Furthermore, we also created 12-class MRcIs in four new patients using the previous data from the 36 patients as training data and obtained tissue sections of the classes 11 and 12, which were significantly higher in high-grade gliomas (HGGs), and those of classes 4, 5 and 9, which were not significantly different between HGGs and low-grade gliomas (LGGs), according to a MRcI-based navigational system. The tissues of classes 11 and 12 showed features of malignant glioma, whereas those of classes 4, 5 and 9 showed LGGs without anaplastic features. These results suggest that the proposed voxel-based clustering method provides new insights into preoperative regional glioma grading. PMID:27456199

  1. "Safe Schools within Safe Communities: A Regional Summit in the Heartland." Policy Briefs Special Report.

    ERIC Educational Resources Information Center

    Huertas, Aurelio, Jr.; Sullivan, Carol

    This report documents the proceedings of a regional policy seminar hosted by the Iowa Department of Education with support from the North Central Regional Educational Laboratory (NCREL) and the Midwest Regional Center for Drug-Free Schools and Communities (MRC). The seminar, "Safe Schools Within Safe Communities," was held on September 19-20,…

  2. Students' Big Three Personality Traits, Perceptions of Teacher Interpersonal Behavior, and Mathematics Achievement: An Application of the Model of Reciprocal Causation

    ERIC Educational Resources Information Center

    Charalampous, Kyriakos; Kokkinos, Constantinos M.

    2014-01-01

    The purpose of the present study was to investigate the application of the Model of Reciprocal Causation (MRC) in examining the relationship between student personality (personal factors), student-perceived teacher interpersonal behavior (environment), and Mathematics achievement (behavior), with the simultaneous investigation of mediating effects…

  3. Tumorigenicity Evaluation of Umbilical Cord Blood-derived Mesenchymal Stem Cells

    PubMed Central

    Park, Sang-Jin; Kim, Hyun-Jung; Kim, Woojin; Kim, Ok-Sun; Lee, Sunyeong; Han, Su-Yeon; Jeong, Eun Ju; Park, Hyun-shin; Kim, Hea-Won; Moon, Kyoung-Sik

    2016-01-01

    Mesenchymal stem cells (MSCs) have been identified in multiple types of tissue and exhibit characteristic self-renewal and multi-lineage differentiation abilities. However, the possibility of oncogenic transformation after transplantation is concerning. In this study, we investigated the tumorigenic potential of umbilical cord blood-derived MSCs (hUCB-MSCs) relative to MRC-5 and HeLa cells (negative and positive controls, respectively) both in vitro and in vivo. To evaluate tumorigenicity in vitro, anchorage-independent growth was assessed using the soft agar colony formation assay. hUCB-MSCs and MRC-5 cells formed few colonies, while HeLa cells formed a greater number of larger colonies, indicating that hUCB-MSCs and MRC-5 cells do not have anchorage-independent proliferation potential. To detect tumorigenicity in vivo, hUCB-MSCs were implanted as a single subcutaneous injection into BALB/c-nu mice. No tumor formation was observed in mice transplanted with hUCB-MSCs or MRC-5 cells based on macroand microscopic examinations; however, all mice transplanted with HeLa cells developed tumors that stained positive for a human gene according to immunohistochemical analysis. In conclusion, hUCB-MSCs do not exhibit tumorigenic potential based on in vitro and in vivo assays under our experimental conditions, providing further evidence of their safety for clinical applications. PMID:27437093

  4. Metaproteomics reveals the major microbial players and their biogeochemical functions in a productive coastal system in the northern South China Sea.

    PubMed

    Dong, Hong-Po; Hong, Yi-Guo; Lu, Songhui; Xie, Lu-Yuan

    2014-12-01

    We study the metaproteome of the GF/F-prefiltered fraction of a microbial community from Shantou coast summer surface waters using a shotgun proteomic approach. Spectra attributed to the marine Roseobacter clade (MRC), the oligotrophic marine Gammaproteobacteria (OMG) group and Flavobacteria dominated in the microbial community, accounting for 21.0%, 23.2% and 12.7% of all of the detected spectra, respectively, whereas the SAR 92 clade accounted for 50% of the OMG group. The abundance of TonB-dependent receptors (TBDRs) was detected and the majority of TBDRs were attributed to the OMG, whereas a large number of ABC transporters matched to the MRC, which suggests niche separation in the microbial community. Expression of proteorhodopsin and RagB/SusD from Flavobacteria facilitates their attachment and growth on algal-derived organic matter. Taurine and glycine betaine appear to be an important source of carbon and nitrogen for the Rhodobacteraceae and SAR11 cluster. The detection of carbon monoxide dehydrogenase, formate dehydrogenase, O-acetylhomoserine sulfhydrylase and sulfur oxidation protein from the MRC demonstrated that members of the MRC play important roles in coastal ocean biogeochemical cycles. This study provides the first insight into functional processes occurring in microbial communities in coastal waters in the South China Sea.

  5. Driving a Semiautonomous Mobile Robotic Car Controlled by an SSVEP-Based BCI.

    PubMed

    Stawicki, Piotr; Gembler, Felix; Volosyak, Ivan

    2016-01-01

    Brain-computer interfaces represent a range of acknowledged technologies that translate brain activity into computer commands. The aim of our research is to develop and evaluate a BCI control application for certain assistive technologies that can be used for remote telepresence or remote driving. The communication channel to the target device is based on the steady-state visual evoked potentials. In order to test the control application, a mobile robotic car (MRC) was introduced and a four-class BCI graphical user interface (with live video feedback and stimulation boxes on the same screen) for piloting the MRC was designed. For the purpose of evaluating a potential real-life scenario for such assistive technology, we present a study where 61 subjects steered the MRC through a predetermined route. All 61 subjects were able to control the MRC and finish the experiment (mean time 207.08 s, SD 50.25) with a mean (SD) accuracy and ITR of 93.03% (5.73) and 14.07 bits/min (4.44), respectively. The results show that our proposed SSVEP-based BCI control application is suitable for mobile robots with a shared-control approach. We also did not observe any negative influence of the simultaneous live video feedback and SSVEP stimulation on the performance of the BCI system. PMID:27528864

  6. A spontaneous mutant of microcystin biosynthesis: genetic characterization and effect on Daphnia.

    PubMed

    Kaebernick, M; Rohrlack, T; Christoffersen, K; Neilan, B A

    2001-11-01

    Microcystis aeruginosa strain MRC is unique in its' possession of the mcyA-J gene cluster, which encodes microcystin synthetase, but its' inability to produce microcystins. M. aeruginosa strain MRD is genetically identical to MRC at numerous genomic loci examined, but produces a variety of microcystins, mainly with the amino acid tyrosine in the molecule. Zooplankton studies with Daphnia galeata and D. pulicaria, using the mutant (MRC) and its' wild type (MRD), showed for the first time that microcystins other than microcystin-LR can be responsible for the poisoning of Daphnia by Microcystis. Regardless of microcystin content, both Daphnia exhibited significantly reduced ingestion rates when fed with either strain of M. aeruginosa compared with the green alga Scenedesmus acutus. A disruption of the molting process in both Daphnia spp. was noted when these species were fed with MRC cells. Such symptoms on Daphnia have not been previously reported for cyanobacteria and may point to a bioactive compound, other than microcystin, which inhibits the hardening of protein-chitin complexes in Daphnia.

  7. Investigating sensitivity, specificity, and area under the curve of the Clinical COPD Questionnaire, COPD Assessment Test, and Modified Medical Research Council scale according to GOLD using St George’s Respiratory Questionnaire cutoff 25 (and 20) as reference

    PubMed Central

    Tsiligianni, Ioanna G; Alma, Harma J; de Jong, Corina; Jelusic, Danijel; Wittmann, Michael; Schuler, Michael; Schultz, Konrad; Kollen, Boudewijn J; van der Molen, Thys; Kocks, Janwillem WH

    2016-01-01

    Background In the GOLD (Global initiative for chronic Obstructive Lung Disease) strategy document, the Clinical COPD Questionnaire (CCQ), COPD Assessment Test (CAT), or modified Medical Research Council (mMRC) scale are recommended for the assessment of symptoms using the cutoff points of CCQ ≥1, CAT ≥10, and mMRC scale ≥2 to indicate symptomatic patients. The current study investigates the criterion validity of the CCQ, CAT and mMRC scale based on a reference cutoff point of St George’s Respiratory Questionnaire (SGRQ) ≥25, as suggested by GOLD, following sensitivity and specificity analysis. In addition, areas under the curve (AUCs) of the CCQ, CAT, and mMRC scale were compared using two SGRQ cutoff points (≥25 and ≥20). Materials and methods Two data sets were used: study A, 238 patients from a pulmonary rehabilitation program; and study B, 101 patients from primary care. Receiver-operating characteristic (ROC) curves were used to assess the correspondence between the recommended cutoff points of the questionnaires. Results Sensitivity, specificity, and AUC scores for cutoff point SGRQ ≥25 were: study A, 0.99, 0.43, and 0.96 for CCQ ≥1, 0.92, 0.48, and 0.89 for CAT ≥10, and 0.68, 0.91, and 0.91 for mMRC ≥2; study B, 0.87, 0.77, and 0.9 for CCQ ≥1, 0.76, 0.73, and 0.82 for CAT ≥10, and 0.21, 1, and 0.81 for mMRC ≥2. Sensitivity, specificity, and AUC scores for cutoff point SGRQ ≥20 were: study A, 0.99, 0.73, and 0.99 for CCQ ≥1, 0.91, 0.73, and 0.94 for CAT ≥10, and 0.66, 0.95, and 0.94 for mMRC ≥2; study B, 0.8, 0.89, and 0.89 for CCQ ≥1, 0.69, 0.78, and 0.8 for CAT ≥10, and 0.18, 1, and 0.81 for mMRC ≥2. Conclusion Based on data from these two different samples, this study showed that the suggested cutoff point for the SGRQ (≥25) did not seem to correspond well with the established cutoff points of the CCQ or CAT scales, resulting in low specificity levels. The correspondence with the mMRC scale seemed satisfactory

  8. An enzyme immunoassay based micro-neutralization test for titration of antibodies to human cytomegalovirus (CMV) and its correlation with direct ELISA measuring CMV IgG antibodies.

    PubMed

    Gupta, C K; Leszczynski, J; Gupta, R K; Siber, G R

    1996-03-01

    An ELISA-based micro-neutralization (Nt) test in MRC-5 cells for titration of neutralizing antibodies against human cytomegalovirus (CMV) in human plasma and preparations of immune globulins was developed to eliminate microscopic reading of cytopathic effect (CPE), a process that is subjective and time consuming. Un-neutralized CMV from the Nt reaction and grown in MRC-5 cells as per the standard micro-Nt test was coated in the same plates by various methods and CMV antigen was quantified by polyclonal or monoclonal CMV antibodies. Optimal coating of plates with CMV antigen (100 TCID50 of virus grown on MRC-5 cells for 7 days) was obtained by freezing/thawing of virus infected MRC-5 cells in phosphate buffered saline, ph 7.2. The CMV antigen treated sequentially with CMV monoclonal antibody to late nuclear protein antigen, goat anti-mouse IgG3 alkaline phosphatase conjugate and phosphatase substrate gave an absorbance of 1 at 410 nm wavelength whereas uninfected MRC-5 cells treated under similar conditions did not show any absorbance. The optimal Nt reaction occurred at 37 degrees C for 1-2 h and was unaffected by complement. At 4 degrees C, CMV was inactivated in 1-2 h. The antibody titres were affected by the virus dose used in the Nt test over a range of 20 to 798 TCID50. When the titre was determined against a reference serum, the effect of virus dose on the Nt titre was reduced. Complete neutralization virus read microscopically correlated with ELISA absorbance of < 0.1. CPE produced by approximately 1 TCID50 of CMV showed an absorbance of 0.1 or more. The correlation coefficient (r) between Nt titres and CMV IgG antibodies determined by ELISA was 0.69 (P < 0.001) for 257 human plasma samples and 0.85 (P < 0.001) for 50 immune globulin preparations.

  9. Production mask composition checking flow

    NASA Astrophysics Data System (ADS)

    Ma, Shou-Yuan; Yang, Chuen-Huei; Tsai, Joe; Wang, Alice; Lin, Roger; Lee, Rachel; Deng, Erwin; Lin, Ling-Chieh; Liao, Hung-Yueh; Tsai, Jenny; Bowhill, Amanda; Vu, Hien; Russell, Gordon

    2016-05-01

    The mask composition checking flow is an evolution of the traditional mask rule check (MRC). In order to differentiate the flow from MRC, we call it Mask Data Correctness Check (MDCC). The mask house does MRC only to identify process limitations including writing, etching, metrology, etc. There still exist many potential errors that could occur when the frame, main circuit and dummies all together form a whole reticle. The MDCC flow combines the design rule check (DRC) and MRC concepts to adapt to the complex patterns in today's wafer production technologies. Although photomask data has unique characteristics, the MRC tool in Calibre® MDP can easily achieve mask composition by using the Extended MEBES job deck (EJB) format. In EJB format, we can customize the combination of any input layers in an IC design layout format, such as OASIS. Calibre MDP provides section-based processing for many standard verification rule format (SVRF) commands that support DRC-like checks on mask data. Integrating DRC-like checking with EJB for layer composition, we actually perform reticle-level DRC, which is the essence of MDCC. The flow also provides an early review environment before the photomask pattern files are available. Furthermore, to incorporate the MDCC in our production flow, runtime is one of the most important indexes we consider. When the MDCC is included in the tape-out flow, the runtime impact is very limited. Calibre, with its multi-threaded processes and good scalability, is the key to achieving acceptable runtime. In this paper, we present real case runtime data for 28nm and 14nm technology nodes, and prove the practicability of placing MDCC into mass production.

  10. Colonoscopy detects significantly more flat adenomas than 3-tesla magnetic resonance colonography: a pilot trial

    PubMed Central

    Hüneburg, Robert; Kukuk, Guido; Nattermann, Jacob; Endler, Christoph; Penner, Arndt-Hendrik; Wolter, Karsten; Schild, Hans; Strassburg, Christian; Sauerbruch, Tilman; Schmitz, Volker; Willinek, Winfried

    2016-01-01

    Background and study aims: Colorectal cancer (CRC) is one of the most common cancers worldwide, and several efforts have been made to reduce its occurrence or severity. Although colonoscopy is considered the gold standard in CRC prevention, it has its disadvantages: missed lesions, bleeding, and perforation. Furthermore, a high number of patients undergo this procedure even though no polyps are detected. Therefore, an initial screening examination may be warranted. Our aim was to compare the adenoma detection rate of magnetic resonance colonography (MRC) with that of optical colonoscopy. Patients and methods: A total of 25 patients with an intermediate risk for CRC (17 men, 8 women; mean age 57.6, standard deviation 11) underwent MRC with a 3.0-tesla magnet, followed by colonoscopy. The endoscopist was initially blinded to the results of MRC and unblinded immediately after examining the distal rectum. Following endoscopic excision, the size, anatomical localization, and appearance of all polyps were described according to the Paris classification. Results: A total of 93 lesions were detected during colonoscopy. These included a malignant infiltration of the transverse colon due to gastric cancer in 1 patient, 28 adenomas in 10 patients, 19 hyperplastic polyps in 9 patients, and 45 non-neoplastic lesions. In 5 patients, no lesion was detected. MRC detected significantly fewer lesions: 1 adenoma (P = 0.001) and 1 hyperplastic polyp (P = 0.004). The malignant infiltration was seen with both modalities. Of the 28 adenomas, 23 (82 %) were 5 mm or smaller; only 4 adenomas 10 mm or larger (14 %) were detected. Conclusion: MRC does not detect adenomas sufficiently independently of the location of the lesion. Even advanced lesions were missed. Therefore, colonoscopy should still be considered the current gold standard, even for diagnostic purposes. PMID:26878043

  11. Use of magnetic resonance cholangiography in the diagnosis of choledocholithiasis: prospective comparison with a reference imaging method

    PubMed Central

    Zidi, S; Prat, F; Le Guen, O; Rondeau, Y; Rocher, L; Fritsch, J; Choury, A; Pelletier, G

    1999-01-01

    Background—Magnetic resonance cholangiography (MRC) is a new technique for non-invasive imaging of the biliary tract. 
Aim—To assess the results of MRC in patients with suspected bile duct stones as compared with those obtained with reference imaging methods. 
Patients/Methods—70 patients (34 men and 36 women, mean (SD) age 71 (15.5) years; median 75) with suspected bile duct stones were included (cholangitis, 33; pancreatitis, three; suspected post-cholecystectomy choledocholithiasis, nine; cholestasis, six; stones suspected on ultrasound or computed tomography scan, 19). MR cholangiograms with two dimensional turbo spin echo sequences were acquired. Endoscopic retrograde cholangiography with or without sphincterotomy (n = 63), endosonography (n = 5), or intraoperative cho- langiography (n = 2) were the reference imaging techniques used for the study and were performed within 12 hours of MRC. Radiologists were blinded to the results of endoscopic retrograde cholangiography and previous investigations. 
Results—49 patients (70%) had bile duct stones on reference imaging (common bile duct, 44, six of which impacted in the papilla; intrahepatic, four; cystic duct stump, one). Stone size ranged from 1 to 20 mm (mean 6.1, median 5.5). Twenty seven patients (55%) had bile duct stones smaller than 6 mm. MRC diagnostic accuracy for bile duct lithiasis was: sensitivity, 57.1%; specificity, 100%; positive predictive value, 100%; negative predictive value, 50%. 
Conclusions—Stones smaller than 6 mm are still often missed by MRC when standard equipment is used. The general introduction of new technical improvements is needed before this method can be considered reliable for the diagnosis of bile duct stones. 

 Keywords: bile duct calculi; endoscopic retrograde cholangiography; magnetic resonance cholangiography PMID:9862837

  12. Circulation effect: response of precipitation δ18O to the ENSO cycle in monsoon regions of China

    NASA Astrophysics Data System (ADS)

    Tan, Ming

    2014-02-01

    Inter-annual variation in the ratio of 18O to 16O of precipitation (δ18Op) in the monsoon regions of China (MRC, area approximately east of 100°E) has not yet been fully analyzed. Based on an analysis of the relationships between the time series of amount-weighted mean annual δ18O in precipitation (δ18Ow) and meteorological variables such as temperature, precipitation as well as atmospheric/oceanic circulation indices, it is recognized that the El Niño-Southern Oscillation (ENSO) cycle appears to be the dominant control on the inter-annual variation in δ18Op in the MRC. Further analysis shows that the trade wind plays a role in governing δ18Ow through affecting the intensity of the different summer monsoon circulations which are closely linked to the weakening (weaker than normal) and strengthening (stronger than normal) of the trade wind and gives the δ18Ow different values at or over inter-annual timescales. The southwest monsoon (SWM) drives long-distance transport of water vapor from Indian Ocean to the MRC, and along this pathway increasing rainout leads to more negative δ18Ow via Rayleigh distillation processes. In contrast, the southeast monsoon (SEM), which is consistent with the changes in the strength of the West Pacific subtropical high, drives short-distance water vapor transport from the West Pacific Ocean to the MRC and leads to less negative δ18Ow. Therefore, the δ18Ow value directly reflects the differences in influence between the SWM, which is strong when the SE trade wind is strong, and the SEM, which is strong when the SE trade wind is weak. In addition, the South China Sea Monsoon also transports local water vapor as well as plays a role in achieving the synchronization between the δ18Ow and ENSO. The author thus terms the δ18Op rhythm in the MRC the "circulation effect". In turn, the δ18Op variation in the MRC has the potential to provide information on atmospheric circulation and the signal of δ18Op recorded in natural archives

  13. Application of the new GOLD COPD staging system to a US primary care cohort, with comparison to physician and patient impressions of severity

    PubMed Central

    Mapel, Douglas W; Dalal, Anand A; Johnson, Phaedra T; Becker, Laura K; Hunter, Alyssa Goolsby

    2015-01-01

    Background In 2011, the traditional Global Initiative for Chronic Obstructive Lung Disease (GOLD) COPD spirometry-based severity classification system was revised to also include exacerbation history and COPD Assessment Test (CAT) and modified Medical Research Council Dyspnea Scale (mMRC) scores. This study examined how COPD patients treated in primary care are reclassified by the new GOLD system compared to the traditional system, and each system’s level of agreement with patient’s or physician’s severity assessments. Methods In this US multicenter cross-sectional study, COPD patients were recruited by 83 primary care practitioners (PCPs) to complete spirometry testing and a survey. Patients were classified by the traditional spirometry-based system (stages 1–4) and under the new system (grades A, B, C, D) using spirometry, exacerbation history, mMRC, and/or CAT results. Concordance between physician and patient-reported severity, spirometry stage, and ABCD grade based on either mMRC or CAT scores was examined. Results Data from 445 patients with spirometry-confirmed COPD were used. As compared to the traditional system, the GOLD mMRC system reclassifies 47% of patients, and GOLD CAT system reclassifies 41%, but the distributions are very different. The GOLD mMRC system resulted in relatively equal distributions by ABCD grade (33%, 22%, 19%, 26%, respectively), but the GOLD CAT system put most into either B or D groups (9%, 45%, 4%, and 42%). The addition of exacerbation history reclassified only 19 additional patients. Agreement between PCPs’ severity rating or their patients’ self-assessment and the new ABCD grade was very poor (κ=0.17 or less). Conclusion As compared to the traditional system, the GOLD 2011 multidimensional system reclassified nearly half of patients, but how they were reclassified varied greatly by whether the mMRC or CAT questionnaire was chosen. Either way, the new system had little correlation with the PCPs or their patients

  14. Use of the water-table fluctuation method to identify and characterize discrete episodes of positive and zero recharge

    NASA Astrophysics Data System (ADS)

    Horowitz, C.; Nimmo, J. R.; Mitchell, L.

    2011-12-01

    As demand increases for limited water supplies, accurate estimates of groundwater recharge become more important from both a water supply and a water quality perspective. The water table fluctuation (WTF) method is often applied for this purpose. The principle of the WTF method is that recharge is equal to the product of specific yield and the water table rise over a particular time interval or episode. Previous research has demonstrated that recharge estimates based on the WTF method have strong sensitivity to the length of the designated time interval. We have developed a method of choosing time intervals for WTF recharge analysis based on intensity and duration of recharge events, correlating specific events with the rainfall that initiated them. In the absence of recharge, the rate of water-table recession can be taken to have a direct functional relationship with the water-table elevation (H). This relationship is referred to as a master recession curve (MRC). A robust MRC (i.e., one that is accurate over the relevant range of H) is essential for accurate WTF-based estimates of groundwater recharge. Where there is a high degree of subsurface heterogeneity, a simple functional form of the MRC (e.g., one based on the concept of a single pour point) may not accurately represent actual conditions. In a numerical algorithm for determining an MRC, we incorporated consistent criteria which allow the MRC to be based only on data representing receding water-tables during periods of negligible recharge. Another algorithm was created to utilize that MRC in estimations of recharge in an episodic fashion, based on a systematic designation of events, i.e. intervals of recharge and their associated rainfall and intervals of zero recharge, also with associated rainfall. We tested these methods using a data set exhibiting rapid water-table fluctuations at the Masser Site in Pennsylvania. The aquifer medium is a highly fractured sandstone with a small specific yield (0.001 < Sy

  15. Research on diversity receive technology for wireless optical communication using PPM in weak turbulence atmosphere channel

    NASA Astrophysics Data System (ADS)

    Liu, Yang; Zhang, Guo-an

    2014-09-01

    In order to mitigate atmospheric turbulence, the free space optical (FSO) system model with spatial diversity is analyzed based on intensity detection pulse position modulation (PPM) in the weak turbulence atmosphere. The slot error rate (SER) calculating formula of the system without diversity is derived under pulse position modulation firstly. Then as a benchmark, independent of identical distribution, the average slot error rates of the three linear combining technologies, which are the maximal ratio combining (MRC), equal gain combining (EGC) and selection combining (SelC), are compared. Simulation results show that the performance of system is the best improved by MRC, followed by EGC, and is poor by SelC, but SelC is simpler and more convenient. Spatial diversity is efficient to improve the performance and has strong ability on resistance to atmospheric channel decline. The above scheme is more suitable for optical wireless communication systems.

  16. Bronchoscopic lung volume reduction in a single-lung transplant recipient with natal lung hyperinflation: a case report.

    PubMed

    Pato, O; Rama, P; Allegue, M; Fernández, R; González, D; Borro, J M

    2010-06-01

    After single lung transplantation for emphysema native lung hyperinflation is a common complication that may cause respiratory failure. Herein we have reported satisfactory bronchoscopic lung volume reduction in a left single-lung transplant recipient with native lung hyperinflation, who suffered from Medical Research Council (MRC) class 3 dyspnea and chest pain. Three endobronchial valves (Zephyr; Emphasys Medical, Redwood, Calif, United States) were placed into the segmental bronchi of the right upper lobe, using videobronchoscopy under general anesthesia. Postoperative chest computed tomography revealed subsegmental atelectasis in that lobe. The clinical benefit was an improved MRC dyspnea class from 3 to 2, which was still present at 4 months after the procedure, although there were no remarkable changes in spirometric parameters.

  17. C elegans: a model for exploring the genetics of fat storage.

    PubMed

    McKay, Renée M; McKay, James P; Avery, Leon; Graff, Jonathan M

    2003-01-01

    To gain insights into the genetic cascades that regulate fat biology, we evaluated C. elegans as an appropriate model organism. We generated worms that lack two transcription factors, SREBP and C/EBP, crucial for formation of mammalian fat. Worms deficient in either of these genes displayed a lipid-depleted phenotype-pale, skinny, larval-arrested worms that lack fat stores. On the basis of this phenotype, we used a reverse genetic screen to identify several additional genes that play a role in worm lipid storage. Two of the genes encode components of the mitochondrial respiratory chain (MRC). When the MRC was inhibited chemically in worms or in a mammalian adipocyte model, fat accumulation was markedly reduced. A third encodes lpd-3, whose homolog is also required for fat storage in a mammalian model. These data suggest that C. elegans is a genetically tractable model to study the mechanisms that underlie the biology of fat-storing tissues.

  18. Hand weakness in Charcot-Marie-Tooth disease 1X.

    PubMed

    Arthur-Farraj, P J; Murphy, S M; Laura, M; Lunn, M P; Manji, H; Blake, J; Ramdharry, G; Fox, Z; Reilly, M M

    2012-07-01

    There have been suggestions from previous studies that patients with Charcot-Marie-Tooth disease (CMT) have weaker dominant hand muscles. Since all studies to date have included a heterogeneous group of CMT patients we decided to analyse hand strength in 43 patients with CMT1X. We recorded handedness and the MRC scores for the first dorsal interosseous and abductor pollicis brevis muscles, median and ulnar nerve compound motor action potentials and conduction velocities in dominant and non-dominant hands. Twenty-two CMT1X patients (51%) had a weaker dominant hand; none had a stronger dominant hand. Mean MRC scores were significantly higher for first dorsal interosseous and abductor pollicis brevis in non-dominant hands compared to dominant hands. Median nerve compound motor action potentials were significantly reduced in dominant compared to non-dominant hands. We conclude that the dominant hand is weaker than the non-dominant hand in patients with CMT1X.

  19. Hand weakness in Charcot-Marie-Tooth disease 1X

    PubMed Central

    Arthur-Farraj, P.J.; Murphy, S.M.; Laura, M.; Lunn, M.P.; Manji, H.; Blake, J.; Ramdharry, G.; Fox, Z.; Reilly, M.M.

    2012-01-01

    There have been suggestions from previous studies that patients with Charcot–Marie–Tooth disease (CMT) have weaker dominant hand muscles. Since all studies to date have included a heterogeneous group of CMT patients we decided to analyse hand strength in 43 patients with CMT1X. We recorded handedness and the MRC scores for the first dorsal interosseous and abductor pollicis brevis muscles, median and ulnar nerve compound motor action potentials and conduction velocities in dominant and non-dominant hands. Twenty-two CMT1X patients (51%) had a weaker dominant hand; none had a stronger dominant hand. Mean MRC scores were significantly higher for first dorsal interosseous and abductor pollicis brevis in non-dominant hands compared to dominant hands. Median nerve compound motor action potentials were significantly reduced in dominant compared to non-dominant hands. We conclude that the dominant hand is weaker than the non-dominant hand in patients with CMT1X. PMID:22464564

  20. Controller development of photo bioreactor for closed-loop regulation of O2 production based on ANN model reference control and computer simulation

    NASA Astrophysics Data System (ADS)

    Hu, Dawei; Zhang, Houkai; Zhou, Rui; Li, Ming; Sun, Yi

    2013-02-01

    When Bioregenerative Life Support System (BLSS) is used for long-term deep space exploration in the future, it is possible to perform closed-loop control on growth of microalgae to effectively regulate O2 production process in emergencies. However, designing controller of microalgae cultivating device (MCD) by means of traditional methods is very difficult or even impossible due to its highly nonlinearity and large operation scope. In our research, the Artificial Neural Network Model Reference Control (ANN-MRC) method was therefore utilized for model identification and controller design for O2 production process of a specific MCD prototype—photo bioreactor (PBR), based on actual experiment and computer simulation. The results demonstrated that the ANN-MRC servo controller could robustly and self-adaptively control and regulate the light intensity of PBR to make O2 concentrations in vent pipe be in line with step reference concentrations with prescribed dynamic response performance.

  1. Protein-Phospholipid Interactions in Nonclassical Protein Secretion: Problem and Methods of Study

    PubMed Central

    Prudovsky, Igor; Kumar, Thallapuranam Krishnaswamy Suresh; Sterling, Sarah; Neivandt, David

    2013-01-01

    Extracellular proteins devoid of signal peptides use nonclassical secretion mechanisms for their export. These mechanisms are independent of the endoplasmic reticulum and Golgi. Some nonclassically released proteins, particularly fibroblast growth factors (FGF) 1 and 2, are exported as a result of their direct translocation through the cell membrane. This process requires specific interactions of released proteins with membrane phospholipids. In this review written by a cell biologist, a structural biologist and two membrane engineers, we discuss the following subjects: (i) Phenomenon of nonclassical protein release and its biological significance; (ii) Composition of the FGF1 multiprotein release complex (MRC); (iii) The relationship between FGF1 export and acidic phospholipid externalization; (iv) Interactions of FGF1 MRC components with acidic phospholipids; (v) Methods to study the transmembrane translocation of proteins; (vi) Membrane models to study nonclassical protein release. PMID:23396106

  2. Quinol derivatives as potential trypanocidal agents

    PubMed Central

    Capes, Amy; Patterson, Stephen; Wyllie, Susan; Hallyburton, Irene; Collie, Iain T.; McCarroll, Andrew J.; Stevens, Malcolm F.G.; Frearson, Julie A.; Wyatt, Paul G.; Fairlamb, Alan H.; Gilbert, Ian H.

    2012-01-01

    Quinols have been developed as a class of potential anti-cancer compounds. They are thought to act as double Michael acceptors, forming two covalent bonds to their target protein(s). Quinols have also been shown to have activity against the parasite Trypanosoma brucei, the causative organism of human African trypanosomiasis, but they demonstrated little selectivity over mammalian MRC5 cells in a counter-screen. In this paper, we report screening of further examples of quinols against T. brucei. We were able to derive an SAR, but the compounds demonstrated little selectivity over MRC5 cells. In an approach to increase selectivity, we attached melamine and benzamidine motifs to the quinols, because these moieties are known to be selectively concentrated in the parasite by transporter proteins. In general these transporter motif-containing analogues showed increased selectivity; however they also showed reduced levels of potency against T. brucei. PMID:22264753

  3. An animal component free medium that promotes the growth of various animal cell lines for the production of viral vaccines.

    PubMed

    Rourou, Samia; Ben Ayed, Yousr; Trabelsi, Khaled; Majoul, Samy; Kallel, Héla

    2014-05-19

    IPT-AFM is a proprietary animal component free medium that was developed for rabies virus (strain LP 2061) production in Vero cells. In the present work, we demonstrated the versatility of this medium and its ability to sustain the growth of other cell lines and different virus strains. Here, three models were presented: Vero cells/rabies virus (strain LP 2061), MRC-5 cells/measles virus (strain AIK-C) and BHK-21 cells/rabies virus (strain PV-BHK21). The cell lines were first adapted to grow in IPT-AFM, by progressive reduction of the amount of serum in the culture medium. After their adaptation, BHK-21 cells grew in suspension by forming clumps, whereas MRC-5 cells remained adherent. Then, kinetics of cell growth were studied in agitated cultures for both cell lines. In addition, kinetics of virus replication were investigated.

  4. Blinking in nanoscale systems: a universal theoretical framework

    NASA Astrophysics Data System (ADS)

    Volkan-Kacso, Sandor; Frantsuzov, Pavel; Janko, Boldizsar

    2012-02-01

    Fluctuations of fluorescence intensity (blinking) is observed in many different kinds of optically active nanoscale objects. These fluctuations with extremely long-term correlations manifest on timescales longer than seconds and were observed in the emission of colloidal and self-assembled quantum dots, nanorods, nanowires, and some organic dyes. We suggest the idea of a universal physical mechanism underlying the blinking phenomenon. Here we show that the features of this universal mechanism can be captured phenomenologically by the multiple recombination center model (MRC) we proposed in a recent work to explaining single colloidal QD intermittency. Within the framework of the MRC model we qualitatively explain all the important features of fluorescence intensity fluctuations for a broad spectrum of nanoscale emitters.

  5. Synergistic effects by combination of ganciclovir and tricin on human cytomegalovirus replication in vitro.

    PubMed

    Yamada, Rie; Suda, Hideki; Sadanari, Hidetaka; Matsubara, Keiko; Tuchida, Yuuzo; Murayama, Tsugiya

    2016-01-01

    It has been demonstrated as the first report that combination treatment with ganciclovir (GCV) and tricin (4',5,7-trihydroxy-3',5' -dimethoxyflavone), a derivative of Sasa albo-marginata, after human cytomegalovirus (HCMV) infection has synergistic effects on both infectious virus production and HCMV DNA synthesis in the human embryonic fibroblast cell line MRC-5. In this paper, we examined the anti-HCMV effects of GCV plus various concentrations of tricin, and tricin plus various concentrations of GCV in MRC-5 cells. We found that expression of the HCMV UL54 gene was significantly inhibited by combination of GCV with tricin when compared with GCV mono-treatment. These results suggest that tricin is a novel compound for combination therapy with GCV against HCMV replication. In addition, reduced-dose combination therapy may provide a direction for treatment in patients with HCMV infection while reducing drug toxicity.

  6. T lymphocytes in rat germinal centres belong to an ER3+ subpopulation of CD4+ cells.

    PubMed Central

    Vonderheide, R H; Hunt, S V

    1990-01-01

    Two-colour immunofluorescence histochemistry showed directly that greater than 90% of CD4+ germinal centre T cells in rat spleen or lymph node examined 7 days after immunization bear the antigen recognized by the monoclonal antibody (mAb) ER3. By contrast, only 30-40% of all thoracic duct or lymph node CD4+ cells were ER3+, as determined by two-colour flow cytometry. CD8+ cells were ER3+, but nearly all B cells were ER3-. Thus, germinal centre T cells belong to a subpopulation of CD4+ cells. Because only 25-30% of CD4+ cells that lack higher molecular weight forms of CD45 (i.e. mAb MRC OX32 cells, equivalent to MRC OX22 cells) express ER3, the CD4+ subpopulations defined by ER3 are neither identical nor complementary to the subsets defined by restricted expression of CD45 epitopes. Images Figure 1 PMID:1970805

  7. UNOCAL Parachute Creek Shale Oil Project. Monitoring review committee meeting report. Annual meeting, 1987-1988

    SciTech Connect

    Not Available

    1988-05-25

    The Energy Security Act of 1980 established a program to provide financial assistance to private industry in the construction and operation of commercial-scale synthetic fuels plants. The Parachute Creek Shale Oil Program is one of four projects awarded financial assistance. The support agreement included development of an Environmental Monitoring Plan incorporating existing compliance monitoring and twenty-two supplemental monitoring points for water, air, solid waste, worker health and safety, and socio-economic impacts during the period 1986-1993. A Monitoring Review Committee (MRC) comprised of representatives from the Project, U.S. Department of Treasury, U.S. Department of Energy, U.S. Environmental Protection Agency, and the state convene each year to discuss monitoring information and trends in environmental and health surveillance. This report documents the first annual MRC meeting, held at the Project.

  8. The nature and ethics of natural experiments.

    PubMed

    Dawson, Angus; Sim, Julius

    2015-10-01

    Natural experiments are an important methodology often used to answer research questions that would, otherwise, be impossible to address, or employed because of ethical concerns about the use of randomisation to interventions that carry known risks. The UK Medical Research Council (MRC) recently produced an extremely useful document discussing the nature and significance of natural experiments within medical and public health research. In this paper, however, we suggest that the MRC document's definition of the term 'natural experiment' is insufficiently precise. In response, we offer a taxonomy of different types of natural experiments and related methods, and explore the ethical implications of these different types. We argue that while the ethical issues that may arise within natural experiments in relation to risks of harm or informed consent may differ from those within the randomised controlled trial, they are not thereby less pressing. The implications of the argument are explored and recommendations made for those involved in research governance.

  9. Powder-Metallurgical Bearings For Turbopumps

    NASA Technical Reports Server (NTRS)

    Bhat, B. N.; Humphries, T. S.; Thom, R. L.; Moxson, V.; Friedman, G. I.; Dolan, F. J.; Shipley, R. J.

    1993-01-01

    Bearings fabricated by powder metallurgy developed for use in machines subjected to extremes of temperature, rolling-contact cyclic stresses, and oxidizing or otherwise corrosive fluids. Bearings also extend operating lives of other machines in which bearings required to resist extreme thermal, mechanical, and chemical stresses. One alloy exhibiting outstanding properties was MRC-2001. Resistance to fatigue, stress corrosion cracking, and wear found superior to that of 440C stainless steel.

  10. Molecular cloning and synthesis of biologically active human tissue inhibitor of metalloproteinases in yeast

    SciTech Connect

    Kaczorek, M.; Honore, N.; Ribes, V.; Dehoux, P.; Cornet, P.; Cartwright, T.; Streeck, R.E.

    1987-06-01

    Tissue inhibitor of metalloproteinases (TIMP) is a widely distributed glycoprotein that stochiometrically inactivates metalloproteinases involved in connective tissue catabolism. Here they report the cDNA cloning of TIMP from human fibroblastic MRC5 cells using a single 42-base oligonucleotide probe. Expression in S. cerevisiae of complete TIMP cDNA yielded insoluble protein aggregates. Biologically active TIMP was reconstituted from the yeast product by a denaturation/renaturation procedure.

  11. Chronic effort dyspnea explained by lung function tests and by HRCT and CRX radiographic patterns in COPD: a post-hoc analysis in 51 patients.

    PubMed

    Giuntini, Carlo; Camiciottoli, Gianna; Maluccio, Nazzarena Maria; Mariani, Laura; Lavorini, Federico; Pistolesi, Massimo

    2007-09-01

    This paper is a post-hoc analysis of a previous study performed to investigate the relationship between computerized tomography (CT) and lung function in 51 outpatients with mild-to-moderate COPD. We studied whether changes in lung function and radiographic patterns may help to explain dyspnea, the most disturbing symptom in patients with COPD. The Medical Research Council (MRC) dyspnea scale shows, by univariate analysis, a similar strength of association to CT expiratory lung density and to DL(CO), a functional index of lung parenchymal loss. The MRC dyspnea scale shows a somewhat less strength of association with a small vertical heart on plain chest films. In multivariate analysis, the model with the strongest association to the MRC dyspnea scale (r = 0.76, p < 0.0001) contains 4 explanatory variables (DL(CO), FRC, PaCO(2), and radiographic pattern of pulmonary hypertension). We suggest that diffusing capacity reflects the emphysematous component of hyperinflation, associated by definition with destruction of terminal airspace walls, as distinct from the air trapping component, which is ascribed to airway obstruction and associated with FRC. PaCO(2) mainly reflects the ventilatory components, i.e., ventilatory drive and ventilatory constraints, of pulmonary gas exchange in COPD, while radiographic pattern of pulmonary hypertension likely reflects hypoxic vascular changes, which depend mainly on ventilation/perfusion mismatch and give rise to pulmonary arterial hypertension that may contribute per se to dyspnea. In conclusion, our analysis points out that chronic effort dyspnea variance may account for up to 58% (r(2) = 0.58) by lung function tests and radiographic patterns. Thus, about 42% of the MRC dyspnea variance remains unexplained by this model. On the other hand, dyspnea ascertainment is dependent on subjective behavior and evaluation and in tests is influenced by individual performance and perception. For example in the 6-minute walk test, a similar or

  12. The Role of Mms22p in DNA Damage Response in Candida albicans.

    PubMed

    Yan, Lan; Xiong, Juan; Lu, Hui; Lv, Quan-zhen; Ma, Qian-yao; Côte, Pierre; Whiteway, Malcolm; Jiang, Yuan-ying

    2015-12-01

    To ensure correct DNA replication, eukaryotes have signaling pathways that respond to replication-associated DNA damage and trigger repair. In both Saccharomyces cerevisiae and Schizosaccharomyces pombe, a complex of proteins, including the cullin protein Rtt101p and two adapter proteins Mms22p and Mms1p, is important for proper response to replication stress. We have investigated this system in Candida albicans. In this pathogen, Mms22p is important for recovery from DNA replication damage induced by agents including methylmethane sulfonate, camptothecin, and ionizing radiation. Although no clear ortholog of Mms1p has been identified in C. albicans, loss of either Mms22p or Rtt101p generates similar damage sensitivity, consistent with a common function. In S. cerevisiae, the Mrc1p-Csm3p-Tof1p complex stabilizes stalled replication forks and activates a replication checkpoint and interacts with Mms22p. A similar complex in S. pombe, consisting of the Tof1p and Csm3p orthologs Swi1p and Swi3p, along with the fission yeast Mrc1p, genetically also interacts with Mms22p. Intriguingly in C. albicans only Mrc1p and Csm3p appear involved in damage repair, and Mms22p is required for responding to DNA damage agents in MRC1 or CSM3 conditional mutants. In C. albicans, although the loss of RAD57 greatly impairs response in the pathogen to many DNA-damaging agents, lethality due to camptothecin damage requires concomitant loss of Rad57p and Mms22p, suggesting that Mms22p is only essential for homologous recombination induced by camptothecin. These results establish that although C. albicans uses conserved cellular modules to respond to DNA damage and replication blocks, the specific details of these modules differ significantly from the S. cerevisiae model.

  13. Cost-effectiveness analysis of establishing a distance-education programme for health personnel in Swaziland.

    PubMed

    Kirigia, Joses M; Sambo, Luis G; Phiri, Margaret; Matsembula, Gladys; Awases, Magda

    2002-01-01

    There is a growing conviction among policy-makers that the availability of adequate numbers of well-trained and motivated human resources is a key determinant of health system' s capacity to achieve their health, responsiveness and fairness-improving goals. The objective of this study was to estimate the cost, effectiveness and incremental cost-effectiveness ratios of various distance-education strategies for the health sector in Swaziland; and recommend the most cost-effective option. The distance-education strategies evaluated included: Mobile library services (MLS); micro-resources centers WITHOUT video conferencing in five health centers and four regional hospitals (MRC-VC); micro-resources centers WITH video conferencing in five health centers and four regional hospitals (MRC+VC); centralized resource center WITHOUT video conferencing (CRC-VC); centralized resource center WITH video conferencing (CRC+VC); and status quo (SQ). The incremental cost-effectiveness ratio for MLS was Emalangeni (E) 41,846; MRC-VC was E42,696; MRC+VC was E45,569; CRC-VC was E43,578; CRC+VC was E40,827; the latter being the most cost-effective distance-education strategy. According to policy-makers, this study served to clarify the various distance-education strategies, their costs and their benefits/effectiveness. There is a need for developing in Africa a culture of basing policy and management decisions of such kind on systematic analyses. Of course, economic evaluation will, at most, be a guide to policy- and decision-making, and thus, the onus of decision-making will always be on policy-makers and health-care managers.

  14. Enhancing Floodplain Management in the Lower Mekong River Basin Using Vegetation and Water Cycle Satellite Observations

    NASA Astrophysics Data System (ADS)

    Bolten, J. D.; Spruce, J.; Wilson, R.; Strauch, K.; Doyle, T.; Srinivan, R.; Lakshmi, V.; Gupta, M.

    2014-12-01

    The Lower Mekong River Basin shared by China, Burma, Laos, Thailand, Cambodia, and Vietnam, is considered the lifeblood of Southeast Asia. The Mekong Basin is subject to large hydrological fluctuations on a seasonal and inter-annual basis. The basin remains prone to severe annual floods that continue to cause widespread damage and endanger food security and the livelihood of the millions who dwell in the region. Also the placement of newly planned dams primarily for hydropower in the Lower Mekong Basin may cause damaging social, agriculture and fisheries impacts to the region where we may now likely be at a critical 'tipping point'. The primary goal of this project is to apply NASA and USGS products, tools, and information for improved flood and water management in the Lower Mekong River Basin to help characterize, understand, and predict future changes on the basin. Specifically, we are providing and helping transfer to the Mekong River Commission (MRC) and the member countries of Thailand, Cambodia, Lao, Vietnam, and Burma the enhanced Soil and Water Assessment Tool (SWAT) using remotely sensed surface, ground water, and root zone soil moisture along with improved Land Use and Land Cover (LULC) maps. In order to estimate the flood potential and constrain the SWAT Available Water Capacity model parameter over the region, we are assimilated GRACE Terrestrial Water Storage observations into the Catchment Land Surface Model. In addition, a Graphic Visualization Tool (GVT) as been developed to work in concert with the output of the SWAT model parameterized for the Mekong Basin as an adjunct tool of the MRC Decision Support Framework. The project requires a close coordination of the development and assessment of the enhanced MRC SWAT with the guidance of MRC resource managers and technical advisors. This presentation will evaluate the skill of the enhanced SWAT model using qualitative (i.e., MODIS change detection) and quantitative (e.g., streamflow) metrics over one

  15. Tidal expiratory flow limitation, dyspnoea and exercise capacity in patients with bilateral bronchiectasis.

    PubMed

    Koulouris, N G; Retsou, S; Kosmas, E; Dimakou, K; Malagari, K; Mantzikopoulos, G; Koutsoukou, A; Milic-Emili, J; Jordanoglou, J

    2003-05-01

    In this study the authors investigated whether expiratory flow limitation (FL) is present during tidal breathing in patients with bilateral bronchiectasis (BB) and whether it is related to the severity of chronic dyspnoea (Medical Research Council (MRC) dyspnoea scale), exercise capacity (maximal mechanical power output (WRmax)) and severity of the disease, as assessed by high-resolution computed tomography (HRCT) scoring. Lung function, MRC dyspnoea, HRCT score, WRmax and FL were assessed in 23 stable caucasian patients (six males) aged 56 +/- 17 yrs. FL was assessed at rest both in seated and supine positions. To detect FL, the negative expiratory pressure (NEP) technique was used. The degree of FL was rated using a five-point FL score. WRmax was measured using a cyclo-ergometer. According to the NEP technique, five patients were FL during resting breathing when supine but not seated, four were FL both seated and supine, and 14 were NFL both seated and supine. Furthermore, it was shown that: 1) in stable BB patients FL during resting breathing is common, especially in the supine position; 2) the degree of MRC dyspnoea is closely related to the five-point FL score; 3) WRmax (% pred) is more closely correlated with the MRC dyspnoea score than with the five-point FL score; and 4) HRCT score is closely related to forced expiratory volume in one second % pred but not five-point FL score. In conclusion, flow limitation is common at rest in sitting and supine positions in patients with bilateral bronchiectasis. Flow limitation and reduced exercise capacity are both associated with more severe dyspnoea. Finally, high-resolution computed tomography scoring correlates best with forced expiratory volume in one second.

  16. Effect of cadmium on the expression levels of interleukin-1α and interleukin-10 cytokines in human lung cells

    PubMed Central

    ODEWUMI, CAROLINE; LATINWO, LEKAN M.; SINCLAIR, ANDRE; BADISA, VEERA L.D.; ABDULLAH, AHKINYALA; BADISA, RAMESH B.

    2015-01-01

    Cadmium is an environmentally hazardous metal, which causes toxicity in humans. Inhalation of cigarette smoke and industrial fumes containing cadmium are sources of cadmium exposure. It is responsible for the malfunction of various organs, leading to disease particularly in the lungs, liver and kidneys. In the present study, the effect of cadmium chloride (CdCl2) on cell viability, and the expression levels of interleukin (IL)-1α and IL-10 cytokines at various concentrations and incubation durations were assessed in MRC-9 human normal lung and A549 human lung cancer cells to elucidate the mechanism of cadmium toxicity. Cell viability was measured using a crystal violet dye binding assay. The expression levels of the cytokines were measured by cytokine specific enzyme-linked immunosorbent assay kits. The viability assay results revealed higher sensitivity of the A549 lung cancer cells to CdCl2 compared with the normal MRC-9 lung cells. In the normal MRC-9 lung cells, higher expression levels of the cytokines were observed at the lowest CdCl2 concentration at a shorter exposure time compared with the lung cancer cells. Higher levels of the cytokines were observed in the A549 lung cancer cells at all other times and concentrations compared with the MRC-9 cells, indicating higher levels of inflammation. The cytokine levels were reduced at higher CdCl2 concentrations and longer exposure durations, demonstrating the toxic effect of cadmium. The results indicated that CdCl2 affected the expression levels of the cytokines and led to cytotoxicity in human lung cells, and suggested that compounds which reduce inflammation may prevent cadmium toxicity. PMID:26397147

  17. Assessment of Medical Reserve Corps Volunteers' Emergency Response Willingness Using a Threat- and Efficacy-Based Model

    PubMed Central

    Barnett, Daniel J.; Thompson, Carol B.; Tosatto, Rob; Austin, Brad; Schaffzin, Samuel; Ansari, Armin; Semon, Natalie L.; Balicer, Ran D.; Links, Jonathan M.

    2013-01-01

    The goal of this study was to investigate the willingness of Medical Reserve Corps (MRC) volunteers to participate in public health emergency–related activities by assessing their attitudes and beliefs. MRC volunteers responded to an online survey organized around the Extended Parallel Process Model (EPPM). Respondents reported agreement with attitude/belief statements representing perceived threat, perceived efficacy, and personal/organizational preparedness in 4 scenarios: a weather-related disaster, a pandemic influenza emergency, a radiological (“dirty bomb”) emergency, and an inhalational anthrax bioterrorism emergency. Logistic regression analyses were used to evaluate predictors of volunteer response willingness. In 2 response contexts (if asked and regardless of severity), self-reported willingness to respond was higher among those with a high perceived self-efficacy than among those with low perceived self-efficacy. Analyses of the association between attitude/belief statements and the EPPM profiles indicated that, under all 4 scenarios and with few exceptions, those with a perceived high threat/high efficacy EPPM profile had statistically higher odds of agreement with the attitude/belief statements than those with a perceived low threat/low efficacy EPPM profile. The radiological emergency consistently received the lowest agreement rates for the attitude/belief statements and response willingness across scenarios. The findings suggest that enrollment with an MRC unit is not automatically predictive of willingness to respond in these types of scenarios. While MRC volunteers' self-reported willingness to respond was found to differ across scenarios and among different attitude and belief statements, the identification of self-efficacy as the primary predictor of willingness to respond regardless of severity and if asked highlights the critical role of efficacy in an organized volunteer response context. PMID:23477632

  18. MC-CDMA with frequency domain diversity reception for sectored indoor wireless cellular networks

    NASA Astrophysics Data System (ADS)

    Sibanda, Andrew; Dlodlo, Mqhele E.

    2001-07-01

    A Monte Carlo simulation was conducted to assess the performance of Multi-Carrier Code Division Multiple Access (MC-CDMA) in a sectored cell, in an indoor environment. In each sector, terminal schedule packet transmission using slotted p-persistent Inhibit Sense Multiple Access, while the packets themselves are transmitted using MC-CDMA. The simulated bit error rate performance of MC-CDMA with combining strategies maximal ratio combining (MRC) and equal gain combining (EGC) used in the frequency domain are presented. A comparison is made between analytically determined bit error probability for a single user in an additive white Gaussian noise channel using binary phase shift keying (BPSK), and simulated bit error rate for a single user using MC-CDMA with MRC and EGC. The determination of the number of sectors in a cell is also given. MC-CDMA with diversity combining outperforms BPSK in a non-fading AWGN channel. Further, as the user-number increases, EGC performs better than MRC if these combining strategies are used with MC-CDMA. Finally, the results show the basis for determining the number of sectors in a cell. When using slotted p-persistent ISMA, it is envisaged that only a single user will transmit at a time in a sector.

  19. Design and development of a film-based intervention about teenage men and unintended pregnancy: applying the Medical Research Council framework in practice.

    PubMed

    Aventin, Áine; Lohan, Maria; O'Halloran, Peter; Henderson, Marion

    2015-04-01

    Following the UK Medical Research Council's (MRC) guidelines for the development and evaluation of complex interventions, this study aimed to design, develop and optimise an educational intervention about young men and unintended teenage pregnancy based around an interactive film. The process involved identification of the relevant evidence base, development of a theoretical understanding of the phenomenon of unintended teenage pregnancy in relation to young men, and exploratory mixed methods research. The result was an evidence-based, theory-informed, user-endorsed intervention designed to meet the much neglected pregnancy education needs of teenage men and intended to increase both boys' and girls' intentions to avoid an unplanned pregnancy during adolescence. In prioritising the development phase, this paper addresses a gap in the literature on the processes of research-informed intervention design. It illustrates the application of the MRC guidelines in practice while offering a critique and additional guidance to programme developers on the MRC prescribed processes of developing interventions. Key lessons learned were: (1) know and engage the target population and engage gatekeepers in addressing contextual complexities; (2) know the targeted behaviours and model a process of change; and (3) look beyond development to evaluation and implementation.

  20. Molecular anatomy and regulation of a stable replisome at a paused eukaryotic DNA replication fork.

    PubMed

    Calzada, Arturo; Hodgson, Ben; Kanemaki, Masato; Bueno, Avelino; Labib, Karim

    2005-08-15

    Eukaryotic cells regulate the progression and integrity of DNA replication forks to maintain genomic stability and couple DNA synthesis to other processes. The budding yeast proteins Mrc1 and Tof1 associate with the putative MCM-Cdc45 helicase and limit progression of the replisome when nucleotides are depleted, and the checkpoint kinases Mec1 and Rad53 stabilize such stalled forks and prevent disassembly of the replisome. Forks also pause transiently during unperturbed chromosome replication, at sites where nonnucleosomal proteins bind DNA tightly. We describe a method for inducing prolonged pausing of forks at protein barriers assembled at unique sites on a yeast chromosome, allowing us to examine for the first time the effects of pausing upon replisome integrity. We show that paused forks maintain an intact replisome that contains Mrc1, Tof1, MCM-Cdc45, GINS, and DNA polymerases alpha and epsilon and that recruits the Rrm3 helicase. Surprisingly, pausing does not require Mrc1, although Tof1 and Csm3 are both important. In addition, the integrity of the paused forks does not require Mec1, Rad53, or recombination. We also show that paused forks at analogous barriers in the rDNA are regulated similarly. These data indicate that paused and stalled eukaryotic replisomes resemble each other but are regulated differently.

  1. Nitric oxide signaling and its role in oxidative stress response in Schizosaccharomyces pombe.

    PubMed

    Astuti, Rika Indri; Watanabe, Daisuke; Takagi, Hiroshi

    2016-01-30

    In the fission yeast Schizosaccharomyces pombe, we found that the putative NO dioxygenase SPAC869.02c (named Yhb1) and the S-nitrosoglutathione reductase Fmd2 cooperatively reduced intracellular NO levels as NO-detoxification enzymes. Although both mRNA and protein levels were increased with exogenous NO, their expression patterns were different during growth phases. While treatment with an NO synthase inhibitor in the log phase abrogated both NO production and Yhb1 expression, induction of Fmd2 in the stationary phase was correlated with elevated mitochondrial respiratory chain (MRC) activity, confirmed by the fact that inhibition of MRC complex III led to a decrease in Fmd2 and NO levels. Moreover, NO was localized in the mitochondria in the stationary phase, suggesting that there are two distinctive types of NO signaling in S. pombe. For mitochondria, pretreatment with an NO donor rescued cell growth by repressing generation of reactive oxygen species (ROS) under oxidative stress. DNA microarray analysis revealed that exogenous NO contributes to tolerance to hydrogen peroxide (H2O2) by (i) inhibition of Fe(3+) to Fe(2+) conversion, (ii) upregulation of the H2O2-detoxifying enzymes, and (iii) downregulation of the MRC genes, suggesting that NO plays a pivotal role in the negative feedback system to regulate ROS levels in S. pombe.

  2. Mutations in COX7B cause microphthalmia with linear skin lesions, an unconventional mitochondrial disease.

    PubMed

    Indrieri, Alessia; van Rahden, Vanessa Alexandra; Tiranti, Valeria; Morleo, Manuela; Iaconis, Daniela; Tammaro, Roberta; D'Amato, Ilaria; Conte, Ivan; Maystadt, Isabelle; Demuth, Stephanie; Zvulunov, Alex; Kutsche, Kerstin; Zeviani, Massimo; Franco, Brunella

    2012-11-01

    Microphthalmia with linear skin lesions (MLS) is an X-linked dominant male-lethal disorder associated with mutations in holocytochrome c-type synthase (HCCS), which encodes a crucial player of the mitochondrial respiratory chain (MRC). Unlike other mitochondrial diseases, MLS is characterized by a well-recognizable neurodevelopmental phenotype. Interestingly, not all clinically diagnosed MLS cases have mutations in HCCS, thus suggesting genetic heterogeneity for this disorder. Among the possible candidates, we analyzed the X-linked COX7B and found deleterious de novo mutations in two simplex cases and a nonsense mutation, which segregates with the disease, in a familial case. COX7B encodes a poorly characterized structural subunit of cytochrome c oxidase (COX), the MRC complex IV. We demonstrated that COX7B is indispensable for COX assembly, COX activity, and mitochondrial respiration. Downregulation of the COX7B ortholog (cox7B) in medaka (Oryzias latipes) resulted in microcephaly and microphthalmia that recapitulated the MLS phenotype and demonstrated an essential function of complex IV activity in vertebrate CNS development. Our results indicate an evolutionary conserved role of the MRC complexes III and IV for the proper development of the CNS in vertebrates and uncover a group of mitochondrial diseases hallmarked by a developmental phenotype.

  3. Nitric oxide signaling and its role in oxidative stress response in Schizosaccharomyces pombe.

    PubMed

    Astuti, Rika Indri; Watanabe, Daisuke; Takagi, Hiroshi

    2016-01-30

    In the fission yeast Schizosaccharomyces pombe, we found that the putative NO dioxygenase SPAC869.02c (named Yhb1) and the S-nitrosoglutathione reductase Fmd2 cooperatively reduced intracellular NO levels as NO-detoxification enzymes. Although both mRNA and protein levels were increased with exogenous NO, their expression patterns were different during growth phases. While treatment with an NO synthase inhibitor in the log phase abrogated both NO production and Yhb1 expression, induction of Fmd2 in the stationary phase was correlated with elevated mitochondrial respiratory chain (MRC) activity, confirmed by the fact that inhibition of MRC complex III led to a decrease in Fmd2 and NO levels. Moreover, NO was localized in the mitochondria in the stationary phase, suggesting that there are two distinctive types of NO signaling in S. pombe. For mitochondria, pretreatment with an NO donor rescued cell growth by repressing generation of reactive oxygen species (ROS) under oxidative stress. DNA microarray analysis revealed that exogenous NO contributes to tolerance to hydrogen peroxide (H2O2) by (i) inhibition of Fe(3+) to Fe(2+) conversion, (ii) upregulation of the H2O2-detoxifying enzymes, and (iii) downregulation of the MRC genes, suggesting that NO plays a pivotal role in the negative feedback system to regulate ROS levels in S. pombe. PMID:26645666

  4. Yield grades and cutability of carcass beef with and without kidney and pelvic fat.

    PubMed

    Crouse, J D; Koch, R M; Dikeman, M E

    1986-10-01

    Cut-out data from 2,550 steer carcasses representing British, Continental and Zebu breeding were analyzed to evaluate yield grade classes based on three equations: 1) Ya = 2.5 + .984 AFT + .0084 HCW - .05 REA + .2 KPF; 2) Yb = same as Ya with intercept changed to 3.2 and KPF deleted; 3) Yc = 3.0 + .984 AFT + .0041 HCW - .03 REA, as proposed by USDA in 1984; where AFT = adjusted fat thickness (cm), HCW = hot carcass weight (kg), REA = rib-eye area (cm2), and KPF = kidney and pelvic fat (%). Essentially boneless, closely trimmed (8 mm) roasts and steaks of the four major retail cuts (MRC) were made from one side of each carcass. Cutability was calculated as: Ca, % = 100 (MRC/side) and Cb,c % = 100 (MRC/side, KPF removed). Cutability increased (P less than .01) an average of two percentage points when KPF was removed. In general, removing KPF from the estimation of cutability and changing the coefficients for REA and HCW resulted in a decrease in the number of carcasses yield graded 1 or 4 and an increase in the number of carcasses in yield grade 2. Redistribution of carcasses was greater for Yc than for Yb. Carcasses classified with equation Yc tended (P greater than .05) to have greater cutability in yield grades 1 and 2, and lower (P less than .01) cutability in yield grades 3, 4 and 5.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. The effect of artichoke (Cynara scolymus L.) extract on respiratory chain system activity in rat liver mitochondria.

    PubMed

    Juzyszyn, Z; Czerny, B; Myśliwiec, Z; Pawlik, A; Droździk, M

    2010-06-01

    The effect of artichoke extract on mitochondrial respiratory chain (MRC) activity in isolated rat liver mitochondria (including reaction kinetics) was studied. The effect of the extract on the activity of isolated cytochrome oxidase was also studied. Extract in the range of 0.68-2.72 microg/ml demonstrated potent and concentration-dependent inhibitory activity. Concentrations > or =5.4 microg/ml entirely inhibited MRC activity. The succinate oxidase system (MRC complexes II-IV) was the most potently inhibited, its activity at an extract concentration of 1.36 microg/ml being reduced by 63.3% compared with the control (p < 0.05). The results suggest a complex inhibitory mechanism of the extract. Inhibition of the succinate oxidase system was competitive (K(i) = 0.23 microg/ml), whereas isolated cytochrome oxidase was inhibited noncompetitively (K(i) = 126 microg/ml). The results of this study suggest that the salubrious effects of artichoke extracts may rely in part on the effects of their active compounds on the activity of the mitochondrial respiratory chain system.

  6. Design and development of a film-based intervention about teenage men and unintended pregnancy: applying the Medical Research Council framework in practice.

    PubMed

    Aventin, Áine; Lohan, Maria; O'Halloran, Peter; Henderson, Marion

    2015-04-01

    Following the UK Medical Research Council's (MRC) guidelines for the development and evaluation of complex interventions, this study aimed to design, develop and optimise an educational intervention about young men and unintended teenage pregnancy based around an interactive film. The process involved identification of the relevant evidence base, development of a theoretical understanding of the phenomenon of unintended teenage pregnancy in relation to young men, and exploratory mixed methods research. The result was an evidence-based, theory-informed, user-endorsed intervention designed to meet the much neglected pregnancy education needs of teenage men and intended to increase both boys' and girls' intentions to avoid an unplanned pregnancy during adolescence. In prioritising the development phase, this paper addresses a gap in the literature on the processes of research-informed intervention design. It illustrates the application of the MRC guidelines in practice while offering a critique and additional guidance to programme developers on the MRC prescribed processes of developing interventions. Key lessons learned were: (1) know and engage the target population and engage gatekeepers in addressing contextual complexities; (2) know the targeted behaviours and model a process of change; and (3) look beyond development to evaluation and implementation. PMID:25483572

  7. Review of systemic therapies for locally advanced and metastatic rectal cancer

    PubMed Central

    Osipov, Arsen; Tan, Carlyn; Tuli, Richard; Hendifar, Andrew

    2015-01-01

    Rectal cancer, along with colon cancer, is the second leading cause of cancer-related deaths in the U.S. Up to a quarter of patients have metastatic disease at diagnosis and 40% will develop metastatic disease. The past 10 years have been extremely exciting in the treatment of both locally advanced and metastatic rectal cancer (mRC). With the advent of neoadjuvant chemoradiation, increased numbers of patients with locally advanced rectal cancer (LARC) are surviving longer and some are seeing their tumors shrink to sizes that allow for resection. The advent of biologics and monoclonal antibodies has propelled the treatment of mRC further than many could have hoped. Combined with regimens such as FOLFOX or FOLFIRI, median survival rates have been increased to an average of 23 months. However, the combinations of chemotherapy regimens seem endless for rectal cancer. We will review the major chemotherapies available for locally advanced and mRC as well as regimens currently under investigation such as FOLFOXIRI. We will also review vascular endothelial growth factor (VEGF) and epidermal growth factor receptor (EGFR) inhibitors as single agents and in combination with traditional chemotherapy regimens. PMID:25830038

  8. Gastroprotective mechanisms of action of semisynthetic carnosic acid derivatives in human cells.

    PubMed

    Theoduloz, Cristina; Pertino, Mariano Walter; Schmeda-Hirschmann, Guillermo

    2014-01-06

    Carnosic acid (CA) and its semisynthetic derivatives display relevant gastroprotective effects on HCl/ethanol induced gastric lesions in mice. However, little is known on the mechanisms of action of the new compounds. The aim of the present work was to assess the gastroprotective action mechanisms of CA and its derivatives using human cell culture models. A human gastric adenocarcinoma cell line (AGS) and lung fibroblasts (MRC-5) were used to reveal the possible mechanisms involved. The ability of the compounds to protect cells against sodium taurocholate (NaT)-induced damage, and to increase the cellular reduced glutathione (GSH) and prostaglandin E2 (PGE2) content was determined using AGS cells. Stimulation of cell proliferation was studied employing MRC-5 fibroblasts. Carnosic acid and its derivatives 10-18 raised GSH levels in AGS cells. While CA did not increase the PGE2 content in AGS cells, all derivatives significantly stimulated PGE2 synthesis, the best effect being found for the 12-O-indolebutyrylmethylcarnosate 13. A significant increase in MRC-5 fibroblast proliferation was observed for the derivatives 7 and 16-18. The antioxidant effect of the compounds was assessed by the inhibition of lipid peroxidation in human erythrocyte membranes, scavenging of superoxide anion and DPPH discoloration assay. The new CA derivatives showed gastroprotective effects by different mechanisms, including protection against cell damage induced by NaT, increase in GSH content, stimulation of PGE2 synthesis and cell proliferation.

  9. Antioxidant and Antigenotoxic Activities of the Brazilian Pine Araucaria angustifolia (Bert.) O. Kuntze

    PubMed Central

    Souza, Márcia O.; Branco, Cátia S.; Sene, Juliane; DallAgnol, Rafaela; Agostini, Fabiana; Moura, Sidnei; Salvador, Mirian

    2014-01-01

    Polyphenols are natural products with recognized potential in drug discovery and development. We aimed to evaluate the polyphenolic profile of Araucaria angustifolia bracts, and their ability to scavenge reactive species. The antioxidant and antigenotoxic effects of A. angustifolia polyphenols in MRC5 human lung fibroblast cells were also explored. The total polyphenol extract of A. angustifolia was determined by the Folin–Ciocalteu reagent and the chemical composition was confirmed by HPLC. Reactive oxygen species’ scavenging ability was investigated by the 2,2-diphenyl-1-picrylhydrazyl (DPPH) method and superoxide dismutase- and catalase-like activities. The protective effect of the extract in MRC5 cells was carried out by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method and the determination of oxidative lipids, protein, and DNA (alkaline and enzymatic comet assay) damage. Total phenolic content of the A. angustifolia extract was 1586 ± 14.53 mg gallic acid equivalents/100 g of bracts. Catechin, epicatechin, quercetin, and apigenin were the major polyphenols. The extract was able to scavenge DPPH radicals and exhibited potent superoxide dismutase and catalase-like activities. Moreover, A. angustifolia extract significantly protected MRC5 cells against H2O2-induced mortality and oxidative damage to lipids, proteins, and DNA. Therefore, A. angustifolia has potential as a source of bioactive chemical compounds. PMID:26784661

  10. Gastroprotective mechanisms of action of semisynthetic carnosic acid derivatives in human cells.

    PubMed

    Theoduloz, Cristina; Pertino, Mariano Walter; Schmeda-Hirschmann, Guillermo

    2013-01-01

    Carnosic acid (CA) and its semisynthetic derivatives display relevant gastroprotective effects on HCl/ethanol induced gastric lesions in mice. However, little is known on the mechanisms of action of the new compounds. The aim of the present work was to assess the gastroprotective action mechanisms of CA and its derivatives using human cell culture models. A human gastric adenocarcinoma cell line (AGS) and lung fibroblasts (MRC-5) were used to reveal the possible mechanisms involved. The ability of the compounds to protect cells against sodium taurocholate (NaT)-induced damage, and to increase the cellular reduced glutathione (GSH) and prostaglandin E2 (PGE2) content was determined using AGS cells. Stimulation of cell proliferation was studied employing MRC-5 fibroblasts. Carnosic acid and its derivatives 10-18 raised GSH levels in AGS cells. While CA did not increase the PGE2 content in AGS cells, all derivatives significantly stimulated PGE2 synthesis, the best effect being found for the 12-O-indolebutyrylmethylcarnosate 13. A significant increase in MRC-5 fibroblast proliferation was observed for the derivatives 7 and 16-18. The antioxidant effect of the compounds was assessed by the inhibition of lipid peroxidation in human erythrocyte membranes, scavenging of superoxide anion and DPPH discoloration assay. The new CA derivatives showed gastroprotective effects by different mechanisms, including protection against cell damage induced by NaT, increase in GSH content, stimulation of PGE2 synthesis and cell proliferation. PMID:24399049

  11. Ozone phytotoxic potential with regard to fragments of the Atlantic Semi-deciduous Forest downwind of Sao Paulo, Brazil.

    PubMed

    Moura, Bárbara B; Alves, Edenise S; de Souza, Silvia R; Domingos, Marisa; Vollenweider, Pierre

    2014-09-01

    In the Metropolitan Region of Campinas (MRC), Brazil, high levels of primary pollutants contribute to ozone (O3) formation. However, little is known regarding the O3 effects in the tropics. Objectives in this study were to characterize the present levels of O3 pollution and to evaluate the relevance of current concentration-based indices for assessing the phytotoxic potential of O3. Changes in O3 concentrations and precursors at 5 monitoring stations within towns of MRC were analyzed. The daily O3 profile was typical for urban sites and showed little yearly variation. Given the permanently foliated forest canopy, yearly rather than seasonal O3 indices were thus more appropriate for estimating the effective ozone dose. With yearly SUM00, SUM60 and AOT40 of 156, 16 and 14 ppm h and confirmed by evidence of O3 injury in foliage, oxidative stress in the MRC has reached levels high enough to affect trees from the Atlantic Semi-deciduous Forest.

  12. Enhancing the versatility of wireless biopotential acquisition for myoelectric prosthetic control

    NASA Astrophysics Data System (ADS)

    Bercich, Rebecca A.; Wang, Zhi; Mei, Henry; Hammer, Lauren H.; Seburn, Kevin L.; Hargrove, Levi J.; Irazoqui, Pedro P.

    2016-08-01

    Objective. A significant challenge in rehabilitating upper-limb amputees with sophisticated, electric-powered prostheses is sourcing reliable and independent channels of motor control information sufficient to precisely direct multiple degrees of freedom simultaneously. Approach. In response to the expressed needs of clinicians, we have developed a miniature, batteryless recording device that utilizes emerging integrated circuit technology and optimal impedance matching for magnetic resonantly coupled (MRC) wireless power transfer to improve the performance and versatility of wireless electrode interfaces with muscle. Main results. In this work we describe the fabrication and performance of a fully wireless and batteryless EMG recording system and use of this system to direct virtual and electric-powered limbs in real-time. The advantage of using MRC to optimize power transfer to a network of wireless devices is exhibited by EMG collected from an array of eight devices placed circumferentially around a human subject’s forearm. Significance. This is a comprehensive, low-cost, and non-proprietary solution that provides unprecedented versatility of configuration to direct myoelectric prostheses without wired connections to the body. The amenability of MRC to varied coil geometries and arrangements has the potential to improve the efficiency and robustness of wireless power transfer links at all levels of upper-limb amputation. Additionally, the wireless recording device’s programmable flash memory and selectable features will grant clinicians the unique ability to adapt and personalize the recording system’s functional protocol for patient- or algorithm-specific needs.

  13. Dynamic Filament Formation by a Divergent Bacterial Actin-Like ParM Protein

    PubMed Central

    Brzoska, Anthony J.; Jensen, Slade O.; Barton, Deborah A.; Davies, Danielle S.; Overall, Robyn L.; Skurray, Ronald A.; Firth, Neville

    2016-01-01

    Actin-like proteins (Alps) are a diverse family of proteins whose genes are abundant in the chromosomes and mobile genetic elements of many bacteria. The low-copy-number staphylococcal multiresistance plasmid pSK41 encodes ParM, an Alp involved in efficient plasmid partitioning. pSK41 ParM has previously been shown to form filaments in vitro that are structurally dissimilar to those formed by other bacterial Alps. The mechanistic implications of these differences are not known. In order to gain insights into the properties and behavior of the pSK41 ParM Alp in vivo, we reconstituted the parMRC system in the ectopic rod-shaped host, E. coli, which is larger and more genetically amenable than the native host, Staphylococcus aureus. Fluorescence microscopy showed a functional fusion protein, ParM-YFP, formed straight filaments in vivo when expressed in isolation. Strikingly, however, in the presence of ParR and parC, ParM-YFP adopted a dramatically different structure, instead forming axial curved filaments. Time-lapse imaging and selective photobleaching experiments revealed that, in the presence of all components of the parMRC system, ParM-YFP filaments were dynamic in nature. Finally, molecular dissection of the parMRC operon revealed that all components of the system are essential for the generation of dynamic filaments. PMID:27310470

  14. Molecular cloning and expression analysis of mannose receptor C type 1 in grass carp (Ctenopharyngodon idella).

    PubMed

    Wang, Li; Liu, Lichun; Zhou, Yang; Zhao, Xiaoheng; Xi, Mingjun; Wei, Shun; Fang, Rui; Ji, Wei; Chen, Nan; Gu, Zemao; Liu, Xueqin; Wang, Weimin; Asim, Muhammad; Liu, Xiaoling; Lin, Li

    2014-03-01

    Mannose receptor C type 1 (MRC1) is a pattern-recognition receptor (PRR) which plays a significant role in immune responses. Much work on MRC1 has been done in mammals and birds while little in fish. In this study, we cloned and characterized MRC1 in grass carp (gcMR). The full-length gcMR contained 5291bp encoding a putative protein of 1432 amino acids. The predicted amino acid sequences showed that gcMR contained a signal peptide, a cysteine-rich (CR) domain, a fibronectin type II (FN II) domain, eight C-type lectin-like domains (CTLDs), a transmembrane domain and a short cytoplasmic domain. gcMR were constitutively expressed in different organs with the higher expression in spleen and head kidney. During embryonic development, gcMR transcript levels were highest at cleavage stage. The up-regulation expression of gcMR, IL-1β and TNF-α in liver, spleen, head kidney and intestine after Aeromonas hydrophila infection indicating it involved in innate immune regulation during bacterial infections. PMID:24184700

  15. Spial: analysis of subtype-specific features in multiple sequence alignments of proteins

    PubMed Central

    Wuster, Arthur; Venkatakrishnan, A. J.; Schertler, Gebhard F. X.; Babu, M. Madan

    2010-01-01

    Motivation: Spial (Specificity in alignments) is a tool for the comparative analysis of two alignments of evolutionarily related sequences that differ in their function, such as two receptor subtypes. It highlights functionally important residues that are either specific to one of the two alignments or conserved across both alignments. It permits visualization of this information in three complementary ways: by colour-coding alignment positions, by sequence logos and optionally by colour-coding the residues of a protein structure provided by the user. This can aid in the detection of residues that are involved in the subtype-specific interaction with a ligand, other proteins or nucleic acids. Spial may also be used to detect residues that may be post-translationally modified in one of the two sets of sequences. Availability: http://www.mrc-lmb.cam.ac.uk/genomes/spial/; supplementary information is available at http://www.mrc-lmb.cam.ac.uk/genomes/spial/help.html Contact: ajv@mrc-lmb.cam.ac.uk PMID:20880955

  16. Electrical Muscle Stimulation: An Effective Form of Exercise and Early Mobilization to Preserve Muscle Strength in Critically Ill Patients

    PubMed Central

    Karatzanos, Eleftherios; Gerovasili, Vasiliki; Zervakis, Dimitrios; Tripodaki, Elli-Sophia; Apostolou, Kleovoulos; Vasileiadis, Ioannis; Papadopoulos, Emmanouil; Mitsiou, Georgios; Tsimpouki, Dimitra; Routsi, Christina; Nanas, Serafim

    2012-01-01

    Purpose. This is a secondary analysis of previously published data to investigate the effects of electrical muscle stimulation (EMS) on strength of various muscle groups in critically ill patients. Methods. One hundred forty-two consecutive patients, with APACHE II score ≥ 13, were randomly assigned to the EMS or the control group. EMS sessions were applied daily on vastus lateralis, vastus medialis, and peroneus longus of both lower extremities. Various muscle groups were evaluated with the Medical Research Council (MRC) scale for muscle strength. Handgrip strength assessment was also employed. Results. Twenty four patients in the EMS group and 28 patients in the control group were finally evaluated. EMS patients achieved higher MRC scores than controls (P ≤ 0.05) in wrist flexion, hip flexion, knee extension, and ankle dorsiflexion. Collectively, the EMS group performed higher (P < 0.01) in the legs and overall. Handgrip strength correlated (P ≤ 0.01) with the upper and lower extremities' muscle strength and the overall MRC scores. Conclusions. EMS has beneficial effects on the strength of critically ill patients mainly affecting muscle groups stimulated, while it may also affect muscle groups not involved presenting itself as a potential effective means of muscle strength preservation and early mobilization in this patient population. PMID:22545212

  17. Characterization of Rift Valley Fever Virus MP-12 Strain Encoding NSs of Punta Toro Virus or Sandfly Fever Sicilian Virus

    PubMed Central

    Lihoradova, Olga A.; Indran, Sabarish V.; Kalveram, Birte; Lokugamage, Nandadeva; Head, Jennifer A.; Gong, Bin; Tigabu, Bersabeh; Juelich, Terry L.; Freiberg, Alexander N.; Ikegami, Tetsuro

    2013-01-01

    Rift Valley fever virus (RVFV; genus Phlebovirus, family Bunyaviridae) is a mosquito-borne zoonotic pathogen which can cause hemorrhagic fever, neurological disorders or blindness in humans, and a high rate of abortion in ruminants. MP-12 strain, a live-attenuated candidate vaccine, is attenuated in the M- and L-segments, but the S-segment retains the virulent phenotype. MP-12 was manufactured as an Investigational New Drug vaccine by using MRC-5 cells and encodes a functional NSs gene, the major virulence factor of RVFV which 1) induces a shutoff of the host transcription, 2) inhibits interferon (IFN)-β promoter activation, and 3) promotes the degradation of dsRNA-dependent protein kinase (PKR). MP-12 lacks a marker for differentiation of infected from vaccinated animals (DIVA). Although MP-12 lacking NSs works for DIVA, it does not replicate efficiently in type-I IFN-competent MRC-5 cells, while the use of type-I IFN-incompetent cells may negatively affect its genetic stability. To generate modified MP-12 vaccine candidates encoding a DIVA marker, while still replicating efficiently in MRC-5 cells, we generated recombinant MP-12 encoding Punta Toro virus Adames strain NSs (rMP12-PTNSs) or Sandfly fever Sicilian virus NSs (rMP12-SFSNSs) in place of MP-12 NSs. We have demonstrated that those recombinant MP-12 viruses inhibit IFN-β mRNA synthesis, yet do not promote the degradation of PKR. The rMP12-PTNSs, but not rMP12-SFSNSs, replicated more efficiently than recombinant MP-12 lacking NSs in MRC-5 cells. Mice vaccinated with rMP12-PTNSs or rMP12-SFSNSs induced neutralizing antibodies at a level equivalent to those vaccinated with MP-12, and were efficiently protected from wild-type RVFV challenge. The rMP12-PTNSs and rMP12-SFSNSs did not induce antibodies cross-reactive to anti-RVFV NSs antibody and are therefore applicable to DIVA. Thus, rMP12-PTNSs is highly efficacious, replicates efficiently in MRC-5 cells, and encodes a DIVA marker, all of which are

  18. Does the MUNIX Method Reflect Clinical Dysfunction in Amyotrophic Lateral Sclerosis

    PubMed Central

    Gawel, Malgorzata; Kuzma-Kozakiewicz, Magdalena

    2016-01-01

    Abstract The aim of our study was to assess the usefulness of the MUNIX method in reflecting the clinical dysfunction in patients with amyotrophic lateral sclerosis (ALS), as well as to assess an intra-rater reproducibility of MUNIX. The study group consisted of a total of 15 ALS patients. The mean age of symptoms onset was 55 years, and the mean disease duration was 10 months. The muscle strength and patients’ functional status were assessed according to the Medical Research Council (MRC) and by ALS functional rating scale revised (ALSFRS-R), respectively. The MUNIX was performed in 6 muscles: abductor pollicis brevis (APB), abductor digiti minimi (ADM), biceps brachii (BB), tibial anterior (TA), extensor digitorum brevis (EDB), and abductor hallucis (AH), unilaterally, at a less affected side. Both muscle-specific and global MRC and MUNIX scores were calculated. In 11 patients, the study protocol was repeated at least twice every 3 months. An additional testing of the intra-rater reliability was performed at the first visit. There were no significant differences between MUNIX test and re-test values in the APB, ADM, BB, TA, EDB, and AH muscles (P >0.05). The highest variability of the test–retest values was found in the BB muscle (7.53%). Although there was a significant test–retest difference in the global MUNIX score (P = 0.02), the variability of the results was as low as 1.26%. The MUNIX value correlated with the muscle-specific MRC score in ABP, ADM, TA, EDB and AH (P <0.05), and the global MUNIX values correlated with global MRC scores (P <0.05). There was also a significant correlation between the global MUNIX score and the clinical dysfunction measured by the ALSFRS-R scale (P <0.05). The global MUNIX showed a higher monthly decline (4.3%) as compared with ALFRS-R (0.7%) and the MRC global score (0.5%). This study confirms that the MUNIX method is a sensitive, reliable, and accurate tool reflecting both motor dysfunction and disease

  19. Mars Rover Curriculum: Teacher Self Reporting of Increased Frequency and Confidence in their Science and Language Arts Instruction

    NASA Astrophysics Data System (ADS)

    Bering, E. A.; Carlson, C.; Nieser, K.; Slagle, E.

    2013-12-01

    The University of Houston is in the process of developing a flexible program that offers children an in-depth educational experience culminating in the design and construction of their own model Mars rover. The program is called the Mars Rover Model Celebration (MRC). It focuses on students, teachers and parents in grades 3-8. Students design and build a model of a Mars rover to carry out a student selected science mission on the surface of Mars. A total of 65 Mars Rover teachers from the 2012-2013 cohort were invited to complete the Mars Rover Teacher Evaluation Survey. The survey was administered online and could be taken at the convenience of the participant. In total, 29 teachers participated in the survey. Teachers were asked to rate their current level of confidence in their ability to teach specific topics within the Earth and Life Science realms, as well as their confidence in their ability to implement teaching strategies with their students. In addition, they were asked to rate the degree to which they felt their confidence increased in the past year as a result of their participation in the MRC program. The majority of teachers (81-90%) felt somewhat to very confident in their ability to effectively teach concepts related to earth and life sciences to their students. In addition, many of the teachers felt that their confidence in teaching these concepts increased somewhat to quite a bit as a result of their participation in the MRC program (54-88%). The most striking increase in this area was the reported 48% of teachers who felt their confidence in teaching 'Earth and the solar system and universe' increased 'Quite a bit' as a result of their participation in the MRC program. The vast majority of teachers (86-100%) felt somewhat to very confident in their ability to effectively implement all of the listed teaching strategies. In addition, the vast majority reported believing that their confidence increased somewhat to quite a bit as a result of their

  20. Effect of nitric oxide on mitochondrial respiratory activity of human articular chondrocytes

    PubMed Central

    Maneiro, E; Lopez-Armada, M; de Andres, M C; Carames, B; Martin, M; Bonilla, A; del Hoyo, P; Galdo, F; Arenas, J; Blanco, F

    2005-01-01

    Objective: To investigate the effect of nitric oxide (NO) on mitochondrial activity and its relation with the apoptosis of human articular chondrocytes. Materials and methods: Mitochondrial function was evaluated by analysing respiratory chain enzyme complexes, citrate synthase (CS) activities, and mitochondrial membrane potential (Δψm). The activities of the mitochondrial respiratory chain (MRC) complexes (complex I: NADH CoQ1 reductase, complex II: succinate dehydrogenase, complex III: ubiquinol cytochrome c reductase, complex IV: cytochrome c oxidase) and CS were measured in human articular chondrocytes isolated from normal cartilage. The Δψm was measured by 5,5',6,6'-tetracholoro-1,1',3,3'-tetraethylbenzimidazole carbocyanide iodide (JC-1) using flow cytometry. Apoptosis was analysed by flow cytometry. The mRNA expression of caspases was analysed by ribonuclease protection analysis and the detection of protein synthesis by western blotting. Sodium nitroprusside (SNP) was used as an NO compound donor. Results: SNP at concentrations higher than 0.5 mmol/l for 24 hours induced cellular changes characteristic of apoptosis. SNP elicited mRNA expression of caspase-3 and caspase-7 and down regulated bcl-2 synthesis in a dose and time dependent manner. Furthermore, 0.5 mM SNP induced depolarisation of the mitochondrial membrane at 5, 12, and 24 hours. Analysis of the MRC showed that at 5 hours, 0.5 mM SNP reduced the activity of complex IV by 33%. The individual inhibition of mitochondrial complex IV with azide modified the Δψm and induced apoptosis. Conclusions: This study suggests that the effect of NO on chondrocyte survival is mediated by its effect on complex IV of the MRC. PMID:15708893

  1. Complete genome analyses of the first porcine rotavirus group H identified from a South African pig does not provide evidence for recent interspecies transmission events.

    PubMed

    Nyaga, Martin M; Peenze, Ina; Potgieter, Christiaan A; Seheri, L Mapaseka; Page, Nicola A; Yinda, Claude K; Steele, A Duncan; Matthijnssens, Jelle; Mphahlele, M Jeffrey

    2016-03-01

    Rotaviruses (RVs) are classified into eight species/groups (RVA-RVH) according to the migration patterns of their 11 genome segments, as well as by serological and molecular properties of Viral Protein 6 (VP6). In 1997 a new unclassified RV was reported infecting adults in Bangladesh and China. This virus was initially named novel adult diarrhoea rotavirus (ADRV-N), but later renamed as RVH. Since then, RVH has been detected in humans only very sporadically. However, RVH is increasingly being detected in pig populations in the USA, Brazil and Japan, but not yet in Africa. Unfortunately, whole genome sequence data of porcine RVH strains in GenBank is currently restricted to a single strain (SKA-1) from Japan. Porcine diarrhoeic samples were collected in South Africa and analysed for rotavirus using an RVA ELISA and electropherotyping by PAGE. One sample displayed a 4:2:1:1:1:1:1 migration pattern, typical for RVH. In order to further investigate this strain, sequence-independent amplification followed by random sequencing using the 454/Roche GS FLX Sequencer was performed, resulting in the second complete porcine RVH strain (MRC-DPRU1575) available in databases. Phylogenetically, all segments of MRC-DPRU1575 clustered closely with the SKA-1 strain and in some segments with known porcine RVH strains from Brazil and the USA. In contrast, the porcine RVH strains were only distantly related to human RVH strains from Asia and a partial RVH-like strain recently detected in bats from Cameroon. Overall, strain MRC-DPRU1575 is the first complete genome of a porcine RVH from Africa and allows for the development of improved RVH screening methods. Our analyses indicate that RVH strains cluster according to their host species, not suggesting any evidence of recent interspecies transmission events. However, more RVH genomes from a wider host range are needed to better understand their evolutionary pathways and zoonotic potential. PMID:26658066

  2. Dissecting the Origin of Breast Cancer Subtype Stem Cell and the Potential Mechanism of Malignant Transformation

    PubMed Central

    Liu, Dianming; Wang, Shuyuan; Yu, Xuexin; Dai, Enyu; Wang, Jing; Wang, Lihong; Jiang, Wei

    2016-01-01

    Background Breast cancer is the most common incident form of cancer in women including different subtypes. Cancer stem cells (CSCs) have been confirmed to exist in breast cancer. But the research on the origin of breast cancer subtype stem cells (BCSSCs) is still inadequate. Methods We identified the putative origin cells of BCSSCs through comparing gene signatures between BCSSCs and normal mammary cells from multiple perspectives: common signature, expression consistency, functional similarity and shortest path length. First, the potential origin cells were ranked according to these measures separately. Then Q statistic was employed to combine all rank lists into a unique list for each subtype, to prioritize the origin cells for each BCSSC. Next, we identified origin-related gene modules through integrating functional interaction network with differentially expressed genes. Finally, transcription factors of significant gene modules were predicted by MatchTM. Results The results showed that Luminal A CSC was most relevant to luminal progenitor cell or mature luminal cell; luminal B and HER2 CSC were most relevant to bipotent-enriched progenitor cell; basal-like CSC was most relevant to bipotent-enriched progenitor cell or mature luminal cell. Network modules analysis revealed genes related to mitochondrial respiratory chain (MRC) were significantly dysregulated during the origin of luminal B CSC. In addition, SOX10 emerged as a key regulator of MRC. Conclusions Our study supports substantive evidence for the possible origin of four kinds of BCSSCs. Dysfunction of MRC may contribute to the origin of luminal B CSC. These findings may have important implications to treat and prevent breast cancer. PMID:27768723

  3. Productivity potential and monetary evaluation of Bt cotton hybrids under varied agronomic manipulations in semi-arid conditions.

    PubMed

    Singh, Kulvir; Rathore, Pankaj; Gumber, R K

    2014-09-01

    Field experiments comprising three Btcotton hybrids in main, two plant geometries in sub and three nutrient levels in sub sub plots of Split Plot design replicated thrice were conducted at PAU, Regional Research Station, Faridkot during Kharif 2010 and 2011. MRC7361 recorded significantly the highest SCY (3121.6 kg ha(-1)) followed by Bioseed 6488 (2649.5 kg ha(-1)) and RCH134 (2107.4 kg ha(-1)). Statistically improved bolls per plant and boll weight primarily helped MRC7361 in achieving the highest yield. Owing to better fertilizer use efficiency (5.47) and water productivity (649.3 gm(-3)), highest net returns of < or = 101047 ha(-1) were observed with MRC7361 as compared to Bioseed 6488 (< or = 83343 ha(-1)) and RCH134 (< or = 63014 ha(-1)). Bolls per plant and benefit cost ratio was significantly enhanced under wider geometry of 67.5 x 90 cm. Application of 225 kg N, 45 kg P ha(-1) produced significantly higher SCY (2825.9 kg ha(-1)) owing to improved sympods and bolls per plant than 150 kg N, 30 kg P ha(-1) (2374.9 kg ha(-1)) and 187.5 kg N, 37.5 kg P ha(-1) (2677.6 kg ha(-1)). As a result of this, statistically highest net returns of < or = 89552 ha(-1) were obtained with application of 225 kg N, 45 kg Pha(-1). Water productivity improved significantly with each successive increase in the level of nutrients. Contrarily, fertilizer use efficiency exhibited reverse trend with statistically highest value (5.08) for the lowest level of nutrients. PMID:25204056

  4. Change in health status in COPD: a seven-year follow-up cohort study

    PubMed Central

    Sundh, Josefin; Montgomery, Scott; Hasselgren, Mikael; Kämpe, Mary; Janson, Christer; Ställberg, Björn; Lisspers, Karin

    2016-01-01

    Health status is a prognostic factor included in the assessment of chronic obstructive pulmonary disease (COPD). The aim of our study was to examine the associations of clinical factors with change in health status over a 7-year follow-up period. In 2005, 970 randomly selected primary and secondary care patients with a COPD diagnosis completed questionnaires including the Clinical COPD Questionnaire (CCQ); and in 2012, 413 completed the CCQ questionnaire again. Linear regression used difference in mean total CCQ score between 2005 and 2012 as the dependent variable. Independent variables were CCQ score at baseline 2005, sex, age, educational level, body mass index (BMI), smoking status, heart disease, diabetes, depression, number of exacerbations in the previous 6 months, dyspnoea (modified Medical Research Council (mMRC)). Health status worsened from mean total CCQ (s.d.) 2.03 (1.26) in 2005 to 2.16 (1.37) in 2012 (P=0.011). In linear regression with adjustment for baseline CCQ; older age, lower education, higher mMRC and BMI below 25 kg/m2 at baseline were associated with worsened health status in 2012. When sex, age and all statistically significant measures were included simultaneously in the analysis of the main study group, higher mMRC and BMI below 25 kg/m2 were were associated with deteriorated health status (P<0.0001). A higher level of dyspnoea and lower weight were associated with worse health status in COPD. Strategies for decreasing dyspnoea and awareness of the possible increased risk of worsening disease in under- and normal-weight COPD patients are clinically important. PMID:27763623

  5. A computer program for predicting recharge with a master recession curve

    USGS Publications Warehouse

    Heppner, Christopher S.; Nimmo, John R.

    2005-01-01

    Water-table fluctuations occur in unconfined aquifers owing to ground-water recharge following precipitation and infiltration, and ground-water discharge to streams between storm events. Ground-water recharge can be estimated from well hydrograph data using the water-table fluctuation (WTF) principle, which states that recharge is equal to the product of the water-table rise and the specific yield of the subsurface porous medium. The water-table rise, however, must be expressed relative to the water level that would have occurred in the absence of recharge. This requires a means for estimating the recession pattern of the water-table at the site. For a given site there is often a characteristic relation between the water-table elevation and the water-table decline rate following a recharge event. A computer program was written which extracts the relation between decline rate and water-table elevation from well hydrograph data and uses it to construct a master recession curve (MRC). The MRC is a characteristic water-table recession hydrograph, representing the average behavior for a declining water-table at that site. The program then calculates recharge using the WTF method by comparing the measured well hydrograph with the hydrograph predicted by the MRC and multiplying the difference at each time step by the specific yield. This approach can be used to estimate recharge in a continuous fashion from long-term well records. Presented here is a description of the code including the WTF theory and instructions for running it to estimate recharge with continuous well hydrograph data.

  6. Mapping wetlands in the Lower Mekong Basin for wetland resource and conservation management using Landsat ETM images and field survey data.

    PubMed

    MacAlister, Charlotte; Mahaxay, Manithaphone

    2009-05-01

    The Mekong River Basin is considered to be the second most species rich river basin in the world. The 795,000 km(2) catchment encompasses several ecoregions, incorporating biodiverse and productive wetland systems. Eighty percent of the rapidly expanding population of the Lower Mekong Basin (LMB), made up in part by Lao PDR, Thailand, Cambodia and Viet Nam, live in rural areas and are heavily reliant on wetland resources. As the populations of Cambodia and Lao PDR will double in the next 20 years, pressure on natural resources and particularly wetlands can only increase. For development planning, resource and conservation management to incorporate wetland issues, information on the distribution and character of Mekong wetlands is essential. The existing but outdated wetland maps were compiled from secondary landuse-landcover data, have limited coverage, poor thematic accuracy and no meta-data. Therefore the Mekong River Commission (MRC) undertook to produce new wetland coverage for the LMB. As resources, funding and regional capacity are limited, it was determined that the method applied should use existing facilities, be easily adaptable, and replicable locally. For the product to be useful it must be accepted by local governments and decision makers. The results must be of acceptable accuracy (>75%) and the methodology should be relatively understandable to non-experts. In the first stage of this exercise, field survey was conducted at five pilot sites covering a range of typical wetland habitats (MRC wetland classification) to supply data for a supervised classification of Landsat ETM images from the existing MRC archive. Images were analysed using ERDAS IMAGINE and applying Maximum Likelihood Classification. Field data were reserved to apply formal accuracy assessment to the final wetland habitat maps, with resulting accuracy ranging from 77 to 94%. The maps produced are now in use at a Provincial and National level in three countries for resource and

  7. Collisionless Hall MHD Reconnection Dynamics: Is the Nonlinear Reconnection Rate Independent of the Mechanism that Breaks Field Lines?

    NASA Astrophysics Data System (ADS)

    Bhattacharjee, A.; Germaschewski, K.; Wang, X.; Linde, T.; Rosner, R.; Siegel, A.

    2002-12-01

    There has been considerable interest in recent years in collisionless reconnection dynamics governed by the generalized Ohm's law in which electron inertia provides the mechanism for breaking field lines. It has been suggested in several theoretical studies that the nonlinear reconnection dynamics, to leading order, is independent of the mechanism that breaks field lines (that is, electron inertia). We test this suggestion carefully using the new Magnetic Reconnection Code (MRC) developed at the Center for Magnetic Reconnection Studies. The MRC is a new massively parallel code with Adaptive Mesh Refinement (AMR) that integrates the equations of Hall MHD. The use of AMR enables unprecedented levels of resolution of the current and vorticity layers and uncovers interesting secondary dynamics not seen in previous studies. We apply the MRC to the study of two problems, one involving free reconnection caused by a spontaneous and fast collisionless instability, the other involving forced reconnection induced by boundary perturbations on a stable plasma. In the case of free reconnection, over the range of parameters covered by our simulations, it is shown that the nonlinear reconnection rate is near-explosive, and furthermore, that the nonlinear magnetic island width is an invariant function of a dimensionless variable which is the product of the linear growth rate and time. Now, since the linear growth rate is a function of the ion sound radius as well as the electron skin depth, we conclude that the nonlinear reconnection rate is not independent of electron inertia. In the case of forced reconnection, after a slow growth phase, the dynamics exhibits an impulsive growth in the amplitude of the thin current sheet, and a subsequent current disruption mediated by secondary instabilities. These results, in which electron inertia provides the mechanism for breaking field lines, are contrasted with resistive Hall MHD simulations in which resistivity provides the mechanism for

  8. Perivascular M2 Macrophages Stimulate Tumor Relapse after Chemotherapy

    PubMed Central

    Hughes, Russell; Qian, Bin-Zhi; Rowan, Charlotte; Muthana, Munitta; Keklikoglou, Ioanna; Olson, Oakley C.; Tazzyman, Simon; Danson, Sarah; Addison, Christina; Clemons, Mark; Gonzalez-Angulo, Ana Maria; Joyce, Johanna A.; De Palma, Michele; Pollard, Jeffrey W.; Lewis, Claire E.

    2016-01-01

    Tumor relapse after chemotherapy-induced regression is a major clinical problem, because it often involves inoperable metastatic disease. Tumor-associated macrophages (TAM) are known to limit the cytotoxic effects of chemotherapy in preclinical models of cancer. Here, we report that an alternatively activated (M2) subpopulation of TAMs (MRC1+TIE2HiCXCR4Hi) accumulate around blood vessels in tumors after chemotherapy, where they promote tumor revascularization and relapse, in part, via VEGF-A release. A similar perivascular, M2-related TAM subset was present in human breast carcinomas and bone metastases after chemotherapy. Although a small proportion of M2 TAMs were also present in hypoxic tumor areas, when we genetically ablated their ability to respond to hypoxia via hypoxia-inducible factors 1 and 2, tumor relapse was unaffected. TAMs were the predominant cells expressing immunoreactive CXCR4 in chemotherapy-treated mouse tumors, with the highest levels expressed by MRC1+ TAMs clustering around the tumor vasculature. Furthermore, the primary CXCR4 ligand, CXCL12, was upregulated in these perivascular sites after chemotherapy, where it was selectively chemotactic for MRC1+ TAMs. Interestingly, HMOX-1, a marker of oxidative stress, was also upregulated in perivascular areas after chemotherapy. This enzyme generates carbon monoxide from the breakdown of heme, a gas known to upregulate CXCL12. Finally, pharmacologic blockade of CXCR4 selectively reduced M2-related TAMs after chemotherapy, especially those in direct contact with blood vessels, thereby reducing tumor revascularization and regrowth. Our studies rationalize a strategy to leverage chemotherapeutic efficacy by selectively targeting this perivascular, relapse-promoting M2-related TAM cell population. PMID:26269531

  9. Continued development of modeling tools and theory for RF heating

    SciTech Connect

    1998-12-01

    Mission Research Corporation (MRC) is pleased to present the Department of Energy (DOE) with its renewal proposal to the Continued Development of Modeling Tools and Theory for RF Heating program. The objective of the program is to continue and extend the earlier work done by the proposed principal investigator in the field of modeling (Radio Frequency) RF heating experiments in the large tokamak fusion experiments, particularly the Tokamak Fusion Test Reactor (TFTR) device located at Princeton Plasma Physics Laboratory (PPPL). An integral part of this work is the investigation and, in some cases, resolution of theoretical issues which pertain to accurate modeling. MRC is nearing the successful completion of the specified tasks of the Continued Development of Modeling Tools and Theory for RF Heating project. The following tasks are either completed or nearing completion. (1) Anisotropic temperature and rotation upgrades; (2) Modeling for relativistic ECRH; (3) Further documentation of SHOOT and SPRUCE. As a result of the progress achieved under this project, MRC has been urged to continue this effort. Specifically, during the performance of this project two topics were identified by PPPL personnel as new applications of the existing RF modeling tools. These two topics concern (a) future fast-wave current drive experiments on the large tokamaks including TFTR and (c) the interpretation of existing and future RF probe data from TFTR. To address each of these topics requires some modification or enhancement of the existing modeling tools, and the first topic requires resolution of certain theoretical issues to produce self-consistent results. This work falls within the scope of the original project and is more suited to the project`s renewal than to the initiation of a new project.

  10. Bacterial flavin-containing monooxygenase is trimethylamine monooxygenase

    PubMed Central

    Chen, Yin; Patel, Nisha A.; Crombie, Andrew; Scrivens, James H.; Murrell, J. Colin

    2011-01-01

    Flavin-containing monooxygenases (FMOs) are one of the most important monooxygenase systems in Eukaryotes and have many important physiological functions. FMOs have also been found in bacteria; however, their physiological function is not known. Here, we report the identification and characterization of trimethylamine (TMA) monooxygenase, termed Tmm, from Methylocella silvestris, using a combination of proteomic, biochemical, and genetic approaches. This bacterial FMO contains the FMO sequence motif (FXGXXXHXXXF/Y) and typical flavin adenine dinucleotide and nicotinamide adenine dinucleotide phosphate-binding domains. The enzyme was highly expressed in TMA-grown M. silvestris and absent during growth on methanol. The gene, tmm, was expressed in Escherichia coli, and the purified recombinant protein had high Tmm activity. Mutagenesis of this gene abolished the ability of M. silvestris to grow on TMA as a sole carbon and energy source. Close homologs of tmm occur in many Alphaproteobacteria, in particular Rhodobacteraceae (marine Roseobacter clade, MRC) and the marine SAR11 clade (Pelagibacter ubique). We show that the ability of MRC to use TMA as a sole carbon and/or nitrogen source is directly linked to the presence of tmm in the genomes, and purified Tmm of MRC and SAR11 from recombinant E. coli showed Tmm activities. The tmm gene is highly abundant in the metagenomes of the Global Ocean Sampling expedition, and we estimate that 20% of the bacteria in the surface ocean contain tmm. Taken together, our results suggest that Tmm, a bacterial FMO, plays an important yet overlooked role in the global carbon and nitrogen cycles. PMID:22006322

  11. Platinum(II) phenanthroimidazole G-quadruplex ligand induces selective telomere shortening in A549 cancer cells.

    PubMed

    Mancini, Johanna; Rousseau, Philippe; Castor, Katherine J; Sleiman, Hanadi F; Autexier, Chantal

    2016-02-01

    Telomere maintenance, achieved by the binding of protective shelterin capping proteins to telomeres and by either telomerase or a recombination-based alternative lengthening of telomere (ALT) mechanism, is critical for cell proliferation and survival. Extensive telomere shortening or loss of telomere integrity activates DNA damage checkpoints, leading to cell senescence or death. Although telomerase upregulation is an attractive target for anti-cancer therapy, the lag associated with telomere shortening and the potential activation of ALT pose a challenge. An alternative approach is to modify telomere interactions with binding proteins (telomere uncapping). G-quadruplex ligands stabilize structures generated from single-stranded G-rich 3'-telomere end (G-quadruplex) folding, which in principle, cannot be elongated by telomerase, thus leading to telomere shortening. Ligands can also mediate rapid anti-proliferative effects by telomere uncapping. We previously reported that the G-quadruplex ligand, phenylphenanthroimidazole ethylenediamine platinum(II) (PIP), inhibits telomerase activity in vitro[47]. In the current study, a long-term seeding assay showed that PIP significantly inhibited the seeding capacity of A549 lung cancer cells and to a lesser extent primary MRC5 fibroblast cells. Importantly, treatment with PIP caused a significant dose- and time-dependent decrease in average telomere length of A549 but not MRC5 cells. Moreover, cell cycle analysis revealed a significant increase in G1 arrest upon treatment of A549 cells, but not MRC5 cells. Both apoptosis and cellular senescence may contribute to the anti-proliferative effects of PIP. Our studies validate the development of novel and specific therapeutic ligands targeting telomeric G-quadruplex structures in cancer cells.

  12. The effect of the timing of ethanol exposure during early postnatal life on total number of Purkinje cells in rat cerebellum

    PubMed Central

    MIKI, TAKANORI; HARRIS, SIMON; WILCE, PETER; TAKEUCHI, YOSHIKI; BEDI, KULDIP S.

    1999-01-01

    We have previously shown that exposing rats to a high dose of ethanol on postnatal d 5 can affect Purkinje cell numbers in the cerebellum whilst similar exposure on d 10 had no such effect. The question arose whether a longer period of ethanol exposure after d 10 could produce loss of Purkinje cells. We have examined this question by exposing young rats to a relatively high dose (∼420–430 mg/dl) of ethanol for 6 d periods between the ages of either 4 and 9 d or 10 and 15 d of age. Exposure was carried out by placing the rats in an ethanol vapour chamber for 3 h per day during the exposure period. Groups of ethanol-treated (ET), separation controls (SC) and mother-reared controls (MRC) were anaesthetised and killed when aged 30 d by perfusion with buffered 2.5% glutaraldehyde. Stereological methods were used to determine the numbers of Purkinje cells in the cerebellum of each rat. MRC, SC and rats treated with ethanol between 10–15 d of age each had, on average, about 254–258 thousand cerebellar Purkinje cells; the differences between these various groups were not statistically significant. However, the rats treated with ethanol vapour between 4–9 d of age had an average of only about 128000±20000 Purkinje cells per cerebellum. This value was significantly different from both the MRC and group-matched SC animals. It is concluded that the period between 4 and 9 d of age is an extremely vulnerable period during which the rat cerebellar Purkinje cells are particularly susceptible to the effects of a high dose of ethanol. However, a similar level and duration of ethanol exposure commencing after 10 d of age has no significant effect on Purkinje cell numbers. PMID:10386779

  13. Evaluation of Laser Stabilization and Imaging Systems for LCLS-II - Final Paper

    SciTech Connect

    Barry, Matthew

    2015-08-20

    By combining the top performing commercial laser beam stabilization system with the most ideal optical imaging configuration, the beamline for the Linear Accelerator Coherent Light Source II (LCLS-II) will deliver the highest quality and most stable beam to the cathode. To determine the optimal combination, LCLS-II beamline conditions were replicated and the systems tested with a He-Ne laser. The Guidestar-II and MRC active laser beam stabilization systems were evaluated for their ideal positioning and stability. Both a two and four lens optical imaging configuration was then evaluated for beam imaging quality, magnification properties, and natural stability. In their best performances when tested over fifteen hours, Guidestar-II kept the beam stable over approximately 70-110um while the MRC system kept it stable over approximately 90-100um. During short periods of time, Guidestar-II kept the beam stable between 10-20um, but was more susceptible to drift over time, while the MRC system maintained the beam between 30-50um with less overall drift. The best optical imaging configuration proved to be a four lens system that images to the iris located in the cathode room and from there, imaged to the cathode. The magnification from the iris to the cathode was 2:1, within an acceptable tolerance to the expected 2.1:1 magnification. The two lens configuration was slightly more stable in small periods of time (less than 10 minutes) without the assistance of a stability system, approximately 55um compared to approximately 70um, but the four lens configurations beam image had a significantly flatter intensity distribution compared to the two lens configuration which had a Gaussian distribution. A final test still needs to be run with both stability systems running at the same time through the four lens system. With this data, the optimal laser beam stabilization system can be determined for the beamline of LCLS-II.

  14. TOD: a new method to characterize electro-optical system performance

    NASA Astrophysics Data System (ADS)

    Bijl, Piet; Valeton, J. M.

    1998-08-01

    The current standard to characterize Electro-Optical system performance is the MRTD (Minimum Resolvable Temperature Difference) for thermal imagers and the MRC (Minimum Resolvable Contrast) for visual devices. This standard has at least three serious disadvantages: (1) the standard 4-bar test pattern is theoretically and practically unsuitable for 1D or 2D spatially sampled systems such as pixel-array camera's, (2) spatial phase is not taken into account, and (3) the results depend on the observer's subjective decision criterion. We propose an adequate and easily applicable alternative: TOD (Triangle Orientation Discrimination threshold). The TOD is based on an improved test pattern, a better defined observer task, and a solid psychophysical measurement procedure. The new method has theoretical and practical advantages: it is suitable for pixel-array camera's, scanning systems and other (Electro-) Optical imaging systems in both the thermal and vision domain, it has a close relationship to real target acquisition, and the observer task is easy. The results are free from observer bias and allow statistical significance tests. The method lends itself very well for automatic measurement, and can be extended for future sensor systems that include advanced image processing. The TOD curve can be implemented easily in a TA model such as ACQUIRE. An observer performance study with real targets shows that the TOD curve predicts TA performance better than the MRC does. The method has been implemented successfully in a thermal imager field test apparatus called TIPI, and may be implemented in current MRTD and MRC test equipment with little effort.

  15. HST Grism Confirmation of Two z ∼ 2 Structures from the Clusters around Radio-loud AGN (CARLA) Survey

    NASA Astrophysics Data System (ADS)

    Noirot, Gaël; Vernet, Joël; De Breuck, Carlos; Wylezalek, Dominika; Galametz, Audrey; Stern, Daniel; Mei, Simona; Brodwin, Mark; Cooke, Elizabeth A.; Gonzalez, Anthony H.; Hatch, Nina A.; Rettura, Alessandro; Stanford, Spencer Adam

    2016-10-01

    Using Hubble Space Telescope slitless grism data, we report the spectroscopic confirmation of two distant structures at z∼ 2 associated with powerful high-redshift radio-loud active galactic nuclei (AGNs). These rich structures, likely (forming) clusters, are among the most distant structures currently known, and were identified on the basis of Spitzer/IRAC [3.6]–[4.5] color. We spectroscopically confirm nine members in the field of MRC 2036‑254, comprising eight star-forming galaxies and the targeted radio galaxy. The median redshift is z = 2.000. We spectroscopically confirm 10 members in the field of B3 0756+406, comprising 8 star-forming galaxies and 2 AGNs, including the targeted radio-loud quasar. The median redshift is z = 1.986. All confirmed members are within 500 kpc (1 arcmin) of the targeted AGNs. We derive median (mean) star-formation rates of ∼ 35 {M}ȯ {{yr}}-1 (∼ 50 {M}ȯ {{yr}}-1) for the confirmed star-forming members of both structures based on their [O iii]λ 5007 luminosities, and estimate average galaxy stellar masses ≲ 1× {10}11 {M}ȯ based on mid-infrared fluxes and spectral energy distribution modeling. Most of our confirmed members are located above the star-forming main sequence toward starburst galaxies, consistent with clusters at these early epochs being the sites of significant levels of star formation. The structure around MRC 2036‑254 shows an overdensity of IRAC-selected candidate galaxy cluster members consistent with being quiescent galaxies, while the structure around B3 0756+406 shows field values, albeit with many lower limits to colors that could allow an overdensity of faint red quiescent galaxies. The structure around MRC 2036‑254 shows a red sequence of passive galaxy candidates.

  16. BER Performance of Decode-and-Forward Relaying Using Equal-Gain Combining over Rayleigh Fading Channels

    NASA Astrophysics Data System (ADS)

    Vo Nguyen, Bao Quoc; Kong, Hyung Yun

    This paper provides a closed form expression for calculating the bit error rate of the decode-and-forward relay protocol that uses equal-gain combining (EGC) at the destination with an arbitrary number of relays. We have shown that EGC technique for decode-and-forward relay scheme offers remarkable diversity advantage over direct transmission. In addition, we also study the impact of combining techniques on the performance of the system by comparing a system that uses EGC to one that uses maximum ratio combining (MRC) & selection combining (SC). Simulations are performed to confirm our theoretical analysis.

  17. Folic before frolic.

    PubMed

    Austin, Martine

    2012-10-01

    In 1991 studies confirmed that taking folic acid both prior to conception and during the early stages of pregnancy could help reduce the risk of neural tube defects (NTDs) like spina bifida by up to 72 per cent (Medical Research Council (MRC) 1991). Yet despite this knowledge, very little has been done to promote awareness of this in the UK since the mid 1990s, and recent studies show that awareness and intake of folic acid are low. This article introduces a new initiative which aims to boost women's awareness (and most importantly uptake) of folic acid, and highlights the important role midwives can play in creating and maintaining this awareness.

  18. Anticancer activity of chemically prepared shrimp low molecular weight chitin evaluation with the human monocyte leukaemia cell line, THP-1.

    PubMed

    Salah, R; Michaud, P; Mati, F; Harrat, Z; Lounici, H; Abdi, N; Drouiche, N; Mameri, N

    2013-01-01

    In the present study, anticancer activities of chitin, chitosan and low molecular weight chitin were evaluated using a human tumour cell line, THP-1. A molecular weight-activity relationship and an electrostatic interaction-activity relationship were determined. The cytotoxic effects of chitin and derivatives were also evaluated using a normal human foetal lung fibroblastic cell line, MRC-5 and the specific cytotoxicity of chitin and derivatives to tumour cell lines was demonstrated. The high antitumour effect of low molecular weight of chitin was established.

  19. Plans for future neutron facilities within the DOE Office of Energy Research

    SciTech Connect

    Thomas, I.

    1995-10-01

    M.R.C. Greenwood brought out some things about the importance of making sure that the public, who funds our work, knows that there is value to it. Currently, the Basic Energy Sciences (BES) advisory committee has a panel that is doing just that for BES research. I insisted that this panel not be the same folks. It is chaired by an economist and it has several nontechnical members on it. I wanted them to have some, you might say, people off the street on it. I have some confidence that often when you bring things to the people, you get good decisions.

  20. 'Incongruous juxtapositions': the chimaera and Mrs McK.

    PubMed

    Martin, Aryn

    2007-09-01

    A century ago, the German botanist Hans Winkler (best known for coining the term 'genome') accomplished two novel transplantations. First, he produced a single plant that grafted together two completely disparate species: tomato and nightshade. Second, he chose the descriptive word 'chimaera' to name his innovation, transplanting the term from mythology to biology. This paper features Mrs McK, the first human chimera, and thus follows the term from botany to clinical medicine. Her remarkable story, pieced together from the notes, drafts and correspondence of Robert Race and his colleagues at the MRC Blood Group Unit, draws attention to the significance of names and naming.

  1. The possibility of using remote sensing technology of lidar for monitoring ecosystem health by detecting habitat condition

    NASA Astrophysics Data System (ADS)

    Huseyinoglu, M. F.; Salaeva, Z.; Secgin, A.; Allakhverdiev, S. R.; Allakhverdiev, K. R.

    2012-01-01

    Since the emergence of laser and henceforth laser remote sensing in the 1960's, lidar (light detecting and ranging) technology has became a significant tool for the detection of various phenomena like wind direction and intensity, atmospheric temperature, urban and rural topography, forest fires, ocean planktonic development, and detection of various constituants such as tropospheric aerosols, stratospheric ozone, trace chemicals and etc. In 2009, a homemade multiwavelength Raman aerosol lidar (named MRC K09) was designed, developed and installed in the Scientific and Technological Research Council of Turkey (TUBITAK) Marmara Research Center (MRC), and since 21 February 2011, it has been accepted to EARLINET (European Aerosol Research Lidar Network). Since 2009, aerosol spatio-temporal distribution and microphysical properties have been investigated in the extremely industrialized vicinity [1,2]. MRC K09 lidar uses a Quantel Brilliant B Nd:YAG laser (1064 nm) with the second and third optical harmonics at 532 and 355 nm, and a homemade Newtonian 40 cm aperture 120 cm focal length telescope. It has 7 channel spectrum analyzer detecting: parallel and perpendicular polarizations at 355 nm, elastic signals at 532 and 1064 nm, Raman signal of molecular nitrogen at 387 nm and Raman signal of water vapor at 408 nm (excited with 355 laser line), and Raman signal for molecular nitrogen at 608 nm (excited with 532 nm laser line). In Spring 2010, preliminary applications for the determination of forest tree species and of forest health in the Black Sea Area using an aeroborne lidar in collaboration with Bartin University, Bartin, Turkey have been made. In early 2011, a fluorescence module utilizing a Princeton Instruments PI-MAX3 1024x256 resolution CCD camera with a Princeton Instruments Acton SP 2500 0.500 m Imaging Triple Grating Monochromator/Spectograph was connected to the MRC K09 lidar system, and the first remote measurements of chlorophyll from different types of

  2. Fermi-LAT detection of a GeV flare from blazar TXS 0646-176

    NASA Astrophysics Data System (ADS)

    Ciprini, Stefano

    2015-07-01

    The Large Area Telescope (LAT), one of the two instruments on the Fermi Gamma-ray Space Telescope, has observed increasing gamma-ray flux from a source positionally consistent with the flat spectrum radio quasar TXS 0646-176 , also known as MRC 0646-176 and 3FGL J0648.8-1740, with radio counterpart position R.A.: 102.11874 deg, -17.73484 deg, (J2000.0, Petrov et al. 2006, AJ, 131, 1872 ) and with redshift z=1.232 (Hewitt & Burbidge 1993, ApJS, 87, 451).

  3. A novel right ventricle segmentation strategy using local spatio-temporal MRI information with a prior regularizer term

    NASA Astrophysics Data System (ADS)

    Atehortúa, Angélica; Martínez, Fabio; Romero, Eduardo

    2013-11-01

    In this work is presented a novel strategy that tracks the right ventricle (RV) shape during a whole cardiac cycle in magnetic resonance sequences (MRC). The proposed approach obtains a set of spatio-temporal observations from a bidirectional per pixel motion descriptor which are each time fused with prior learned edges. A main advantage of the proposed approach is a robust MRI heart characterization that is regularized by a prior information, obtaining in each cardiac state coherent results. The proposed approach achieves a Dice Score of 0.64 evaluated over 16 patients.

  4. Mars Rover Curriculum: Impact Assessment and Evaluation

    NASA Astrophysics Data System (ADS)

    Bering, E. A., III; Carlson, C.; Nieser, K.; Slagle, E. M.; Jacobs, L. T.; Kapral, A. J.

    2014-12-01

    The University of Houston is in the process of developing a flexible program that offers children an in-depth educational experience culminating in the design and construction of their own model Mars rover: the Mars Rover Model Celebration (MRC). It focuses on students, teachers and parents in grades 3-8. Students design and build a model of a Mars rover to carry out a student selected science mission on the surface of Mars. A total of 140 Mars Rover teachers from the 2012-2013 and 2013-2014 cohorts were invited to complete the Mars Rover Teacher Evaluation Survey. The survey was administered online and could be taken at the convenience of the participant. So far ~40 teachers have participated with responses still coming in. A total of 675 students from the 2013-2014 cohort were invited to submit brief self-assessments of their participation in the program. Teachers were asked to rate their current level of confidence in their ability to teach specific topics within the Earth and Life Science realms, as well as their confidence in their ability to implement teaching strategies with their students. The majority of teachers (81-90%) felt somewhat to very confident in their ability to effectively teach concepts related to earth and life sciences to their students. In addition, many of the teachers felt that their confidence in teaching these concepts increased somewhat to quite a bit as a result of their participation in the MRC program (54-88%). The most striking increase in this area was the reported 48% of teachers who felt their confidence in teaching "Earth and the solar system and universe" increased "Quite a bit" as a result of their participation in the MRC program. The vast majority of teachers (86-100%) felt somewhat to very confident in their ability to effectively implement all of the listed teaching strategies. The most striking increases were the percentage of teachers who felt their confidence increased "Quite a bit" as a result of their participation

  5. Infectivity of human coronavirus strain 229E.

    PubMed

    Macnaughton, M R; Thomas, B J; Davies, H A; Patterson, S

    1980-09-01

    The replication of human coronavirus strain 229E was observed by using indirect immunofluorescence in infected monolayers of MRC continuous cells. By 8 h after infection, bright cytoplasmic fluorescence was detected in cells infected with human coronavirus 229E. Discrete foci of infection were observed from 8 to 16 h after infection in cells infected with high dilutions of human coronavirus 229E; each fluorescent focus corresponded to a single virus infection. A fluorescent focus assay is described, using indirect immunofluorescence, which is more sensitive than the established techniques of tube titration and plaque assay. Particle/infectivity ratios for unpurified and purified virus preparations revealed a considerable drop in infectivity on purification.

  6. Synthesis and biological evaluation of furopyrimidine N,O-nucleosides.

    PubMed

    Romeo, Roberto; Giofrè, Salvatore V; Garozzo, Adriana; Bisignano, Benedetta; Corsaro, Antonino; Chiacchio, Maria A

    2013-09-15

    A series of modified N,O-nucleosides, characterized by the presence of a furopyrimidine moiety, has been synthesized by exploiting a Sonogashira cross coupling reaction of 1-isoxazolidinyl-5-iodouracil with alkynes, followed by treatment with CuI in refluxing TEA/MeOH mixture. The obtained compounds were screened against both RNA and DNA viruses. None of the compounds were endowed with antiviral activity at subtoxic concentrations. However, some of them were able to inhibit proliferation of MRC-5, Vero, BS-C-1 cells by 50% (CC50) at concentrations ranging from 0.7 to 62.5 mM.

  7. Sensitivity Assessment of Ozone Models

    SciTech Connect

    Shorter, Jeffrey A.; Rabitz, Herschel A.; Armstrong, Russell A.

    2000-01-24

    The activities under this contract effort were aimed at developing sensitivity analysis techniques and fully equivalent operational models (FEOMs) for applications in the DOE Atmospheric Chemistry Program (ACP). MRC developed a new model representation algorithm that uses a hierarchical, correlated function expansion containing a finite number of terms. A full expansion of this type is an exact representation of the original model and each of the expansion functions is explicitly calculated using the original model. After calculating the expansion functions, they are assembled into a fully equivalent operational model (FEOM) that can directly replace the original mode.

  8. Fusarium inhibition by wild populations of the medicinal plant Salvia africana-lutea L. linked to metabolomic profiling

    PubMed Central

    2014-01-01

    Background Salvia africana-lutea L., an important medicinal sage used in the Western Cape (South Africa), can be termed a ‘broad-spectrum remedy’ suggesting the presence of a multiplicity of bioactive metabolites. This study aimed at assessing wild S. africana-lutea populations for chemotypic variation and anti-Fusarium properties. Methods Samples were collected from four wild growing population sites (Yzerfontein, Silwerstroomstrand, Koeberg and Brackenfell) and one garden growing location in Stellenbosch. Their antifungal activities against Fusarium verticillioides (strains: MRC 826 and MRC 8267) and F. proliferatum (strains: MRC 6908 and MRC 7140) that are aggressive mycotoxigenic phytopathogens were compared using an in vitro microdilution assay. To correlate antifungal activity to chemical profiles, three techniques viz. Gas chromatography-mass spectrometry (GC-MS); Liquid chromatography-mass spectrometry (LC-MS) and 1H Nuclear Magnetic Resonance (NMR) were employed. Principal Component Analysis (PCA) was applied to the NMR data. The partial least squares-discriminant analysis (PLS-DA) was used to integrate LC-MS and NMR data sets. All statistics were performed with the SIMCA-P + 12.0 software. Results The dichloromethane:methanol (1:1; v/v) extracts of the plant species collected from Stellenbosch demonstrated the strongest inhibition of F. verticillioides and F. proliferatum with minimum inhibitory concentration (MIC) values of 0.031 mg ml-1 and 0.063 mg ml-1 respectively. GC-MS showed four compounds which were unique to the Stellenbosch extracts. By integrating LC-MS and 1H NMR analyses, large chemotype differences leading to samples grouping by site when a multivariate analysis was performed, suggested strong plant-environment interactions as factors influencing metabolite composition. Signals distinguishing the Stellenbosch profile were in the aromatic part of the 1H NMR spectra. Conclusions This study shows the potential of chemotypes of

  9. Quality of reporting of complex healthcare interventions and applicability of the CReDECI list - a survey of publications indexed in PubMed

    PubMed Central

    2013-01-01

    Background The development and evaluation of complex interventions in healthcare has obtained increased awareness. The Medical Research Council’s (MRC) framework for the development and evaluation of complex interventions and its update offers guidance for researchers covering the phases development, feasibility/piloting, and evaluation. Comprehensive reporting of complex interventions enhances transparency and is essential for researchers and policy-makers. Recently, a set of 16 criteria for reporting complex interventions in healthcare (CReDECI) was published. The aim of this study is to evaluate the reporting quality in publications of complex interventions adhering to either the first or the updated MRC framework, and to evaluate the applicability of CReDECI. Methods A systematic PubMed search was conducted. Two reviewers independently checked titles and abstracts for inclusion. Trials on complex interventions adhering to the MRC framework and including an evaluation study in English and German were included. For all included trials and for all publications which reported on phases prior to the evaluation study, related publications were identified via forward citation tracking. The quality of reporting was assessed independently by two reviewers using CReDECI. Inter-rater agreement and time needed to complete the assessment were determined. Results Twenty-six publications on eight trials were included. The number of publications per trial ranged from 1 to 6 (mean 3.25). The trials demonstrate a good reporting quality for the criteria referring to the development and feasibility/piloting. For the criteria addressing the introduction of the intervention and the evaluation, quality of reporting varied widely. Two trials fulfilled 7 and 8 items respectively, five trials fulfilled one to five items and one trial offered no information on any item. The mean number of items with differing ratings per trial was two. The time needed to rate a trial ranged from 30 to

  10. Pioglitazone leads to an inactivation and disassembly of complex I of the mitochondrial respiratory chain

    PubMed Central

    2013-01-01

    Background Thiazolidinediones are antidiabetic agents that increase insulin sensitivity but reduce glucose oxidation, state 3 respiration, and activity of complex I of the mitochondrial respiratory chain (MRC). The mechanisms of the latter effects are unclear. The aim of this study was to determine the mechanisms by which pioglitazone (PGZ), a member of the thiazolidinedione class of antidiabetic agents, decreases the activity of the MRC. In isolated mitochondria from mouse liver, we measured the effects of PGZ treatment on MRC complex activities, fully-assembled complex I and its subunits, gene expression of complex I and III subunits, and [3H]PGZ binding to mitochondrial complexes. Results In vitro, PGZ decreased activity of complexes I and III of the MRC, but in vivo only complex I activity was decreased in mice treated for 12 weeks with 10 mg/kg/day of PGZ. In vitro treatment of isolated liver mitochondria with PGZ disassembled complex I, resulting in the formation of several subcomplexes. In mice treated with PGZ, fully assembled complex I was increased and two additional subcomplexes were found. Formation of supercomplexes CI+CIII2+CIVn and CI+CIII2 decreased in mouse liver mitochondria exposed to PGZ, while formation of these supercomplexes was increased in mice treated with PGZ. Two-dimensional analysis of complex I using blue native/sodium dodecyl sulfate polyacrylamide gel electrophoresis (BN/SDS-PAGE) showed that in vitro PGZ induced the formation of four subcomplexes of 600 (B), 400 (C), 350 (D), and 250 (E) kDa, respectively. Subcomplexes B and C had NADH:dehydrogenase activity, while subcomplexes C and D contained subunits of complex I membrane arm. Autoradiography and coimmunoprecipitation assays showed [3H]PGZ binding to subunits NDUFA9, NDUFB6, and NDUFA6. Treatment with PGZ increased mitochondrial gene transcription in mice liver and HepG2 cells. In these cells, PGZ decreased intracellular ATP content and enhanced gene expression of specific

  11. Fermi-LAT detection of hard spectrum and high-level gamma-ray flare from the blazar PKS 1954-388

    NASA Astrophysics Data System (ADS)

    Cutini, Sara; Ciprini, Stefano; Fermi Large Area Telescope Collaboration

    2015-09-01

    The Large Area Telescope (LAT), one of two instruments on the Fermi Gamma-ray Space Telescope, has observed flaring gamma rays from a source positionally consistent with the flat spectrum radio quasar PKS 1954-388 (also known as MRC 1954-388, RX J1958.0-3845, and 3FGL J1958.0-3847, Acero et al. 2015, ApJS 218, 23), with radio coordinates, (J2000.0), R.A.: 299.499247 deg, Dec.: -38.751766 deg, (Ma et. al. 1998, AJ, 116, 516).

  12. Merging of image data in electron crystallography.

    PubMed

    Arheit, Marcel; Castaño-Diéz, Daniel; Thierry, Raphaël; Abeyrathne, Priyanka; Gipson, Bryant R; Stahlberg, Henning

    2013-01-01

    Electron crystallography of membrane proteins uses cryo-transmission electron microscopy to record images and diffraction patterns of frozen-hydrated 2D crystals. Each two-dimensional (2D) crystal is only imaged once, at one specific tilt angle, and the recorded images can be automatically processed with the 2dx/MRC software package. Processed image data from non-tilted and tilted 2D crystals then need to be merged into a 3D reconstruction of the membrane protein structure. We here describe the process of the 3D merging, using the 2dx software system.

  13. Farewell, king coal!

    PubMed

    Seaton, Anthony

    2016-04-01

    Coal mining provided the power for the industrial development of the West, at great cost to the health of the workforce and, from industrial pollution, of the population. Medical appreciation of the diseases of miners was slow to develop and has been marked by controversy relating to the roles of coal and quartz and the causation of emphysema. Research by the MRC and the British coal industry resolved these issues as the industry itself declined. However, from the research has come an understanding of the influence of inhalation of different inhaled pollutants on human health that has been applied to predicting and preventing possible hazards of developing nanotechnologies.

  14. Mississippi graduate DOE EPSCor trainee project. [First Annual Summary Report

    SciTech Connect

    Wertz, D.L.

    1992-08-01

    The promotion of an aggressive energy research initiative was identified as a goal of the Mississippi Research Consortium (MRC) from its inception in 1986. The Department of Energy EPSCOR Program has provided opportunities to address the needs and enhance the interactive programs of energy-related research in the State of Mississippi. The Mississippi DOE EPSCOR Graduate Traineeships Project is a program of education and research which will (1) increase the number of trained professionals in the energy sciences and technology, particularly those from groups traditionally under-represented in the field, and (2) interface with existing networks of universities, industry, federal, and state institutions involved in energy-related activities.

  15. Mississippi graduate DOE EPSCor trainee project. First annual summary report

    SciTech Connect

    Wertz, D.L.

    1992-08-01

    The promotion of an aggressive energy research initiative was identified as a goal of the Mississippi Research Consortium (MRC) from its inception in 1986. The Department of Energy EPSCOR Program has provided opportunities to address the needs and enhance the interactive programs of energy-related research in the State of Mississippi. The Mississippi DOE EPSCOR Graduate Traineeships Project is a program of education and research which will (1) increase the number of trained professionals in the energy sciences and technology, particularly those from groups traditionally under-represented in the field, and (2) interface with existing networks of universities, industry, federal, and state institutions involved in energy-related activities.

  16. Magnetorheological composites as semi-active elements of dampers

    NASA Astrophysics Data System (ADS)

    Kaleta, Jerzy; Lewandowski, Daniel; Zając, Piotr; Kustroń, Pawel

    2009-02-01

    An original magnetorheological composite (MRC) with porous elastomeric matrix and filled with magnetorheological fluid was created at the work. It was used later on to build a damper working in the shearing mode without friction against external surfaces of the so-called skid. This prototype construction was used for damping free vibrations in the beam. An analysis of the effectiveness in the magnetic field function steering the damper was performed. As a result an important relationship between the change of damping in the material under the influence of the magnetic field and the length of time needed for damping the vibrations in the beam was demonstrated.

  17. Impact Assessment on Teachers of Student-led, Inquiry-based Planetary Science Instruction in Grades 3-8

    NASA Astrophysics Data System (ADS)

    Bering, E. A., III; Slagle, E. M.; Carlson, C.; Nieser, K.

    2015-12-01

    The University of Houston is in the process of developing a flexible program that offers children an in-depth educational experience culminating in the design and construction of their own model Mars rover. The program is called the Mars Rover Model Celebration (MRC). It focuses on students, teachers in grades 3-8. Students design and build a model of a Mars rover to carry out a student selected science mission on Mars. A total of 195 Mars Rover teachers from the 2012-2013, 2013-2014, and 2014-2015 cohorts were invited to complete the Mars Rover Teacher Evaluation Survey. The survey was administered online and could be taken at the convenience of the participant. A total of 1300 students from the 2013-2014 and 2014-2015 cohort wereinvited to submit self-assessments of their participation in the program. Teachers were asked to rate their current level of confidence in their ability to teach specific topics within the Earth and Life Science realms, as well as their confidence in their ability to implement teaching strategies with their students. The majority of teachers (81-90%) felt somewhat to very confident in their ability to effectively teach concepts related to earth and life sciences to their students. In addition, many of the teachers felt that their confidence in teaching these concepts increased somewhat to quite a bit as a result of their participation in the MRC program (54-88%). The most striking increase in this area was the reported 48% of teachers who felt their confidence in teaching "Earth and the solar system and universe" increased "Quite a bit" as a result of their participation in the MRC program. The vast majority of teachers (86-100%) felt somewhat to very confident in their ability to effectively implement all of the listed teaching strategies. The most striking increases were the percentage of teachers who felt their confidence increased "Quite a bit" as a result of their participation in the MRC program in the following areas: "Getting

  18. Spoxazomicins A-C, novel antitrypanosomal alkaloids produced by an endophytic actinomycete, Streptosporangium oxazolinicum K07-0460(T).

    PubMed

    Inahashi, Yuki; Iwatsuki, Masato; Ishiyama, Aki; Namatame, Miyuki; Nishihara-Tsukashima, Aki; Matsumoto, Atsuko; Hirose, Tomoyasu; Sunazuka, Toshiaki; Yamada, Haruki; Otoguro, Kazuhiko; Takahashi, Yōko; Omura, Satoshi; Shiomi, Kazuro

    2011-04-01

    Three novel antitrypanosomal alkaloids, named spoxazomicins A-C, were isolated by silica gel column chromatography and HPLC from the culture broth of a new endophytic actinomycete species, Streptosporangium oxazolinicum K07-0460(T). The structures of the spoxazomicins were elucidated by NMR and X-ray crystal analyses and shown to be new types of pyochelin family antibiotic. Spoxazomicin A showed potent and selective antitrypanosomal activity with an IC₅₀ value of 0.11 μg ml⁻¹ in vitro without cytotoxicity against MRC-5 cells (IC₅₀=27.8 μg ml⁻¹). PMID:21386848

  19. Genetic associations with thalidomide mediated venous thrombotic events in myeloma identified using targeted genotyping

    PubMed Central

    Johnson, David C.; Corthals, Sophie; Ramos, Christine; Hoering, Antje; Cocks, Kim; Dickens, Nicholas J.; Haessler, Jeff; Goldschmidt, Harmut; Child, J. Anthony; Bell, Sue E.; Jackson, Graham; Baris, Dalsu; Rajkumar, S. Vincent; Davies, Faith E.; Durie, Brian G. M.; Crowley, John; Sonneveld, Pieter; Van Ness, Brian

    2008-01-01

    A venous thromboembolism (VTE) with the subsequent risk of pulmonary embolism is a major concern in the treatment of patients with multiple myeloma with thalidomide. The susceptibility to developing a VTE in response to thalidomide therapy is likely to be influenced by both genetic and environmental factors. To test genetic variation associated with treatment related VTE in patient peripheral blood DNA, we used a custom-built molecular inversion probe (MIP)–based single nucleotide polymorphism (SNP) chip containing 3404 SNPs. SNPs on the chip were selected in “functional regions” within 964 genes spanning 67 molecular pathways thought to be involved in the pathogenesis, treatment response, and side effects associated with myeloma therapy. Patients and controls were taken from 3 large clinical trials: Medical Research Council (MRC) Myeloma IX, Hovon-50, and Eastern Cooperative Oncology Group (ECOG) EA100, which compared conventional treatments with thalidomide in patients with myeloma. Our analysis showed that the set of SNPs associated with thalidomide-related VTE were enriched in genes and pathways important in drug transport/metabolism, DNA repair, and cytokine balance. The effects of the SNPs associated with thalidomide-related VTE may be functional at the level of the tumor cell, the tumor-related microenvironment, and the endothelium. The clinical trials described in this paper have been registered as follows: MRC Myeloma IX: ISRCTN68454111; Hovon-50: NCT00028886; and ECOG EA100: NCT00033332. PMID:18805967

  20. Evolution of clinical research: a history before and beyond james lind.

    PubMed

    Bhatt, Arun

    2010-01-01

    The evolution of clinical research traverses a long and fascinating journey. From the first recorded trial of legumes in biblical times to the first randomized controlled of trial of streptomycin in 1946, the history of clinical trial covers a wide variety of challenges - scientific, ethical and regulatory. The famous 1747 scurvy trial conducted by James Lind contained most elements of a controlled trial. The UK Medical Research Council's (MRC) trial of patulin for common cold in 1943 was the first double blind controlled trial. This paved the way for the first randomized control trial of streptomycin in pulmonary tuberculosis carried out in 1946 by MRC of the UK. This landmark trial was a model of meticulousness in design and implementation, with systematic enrolment criteria and data collection compared with the ad hoc nature of other contemporary research. Over the years, as the discipline of controlled trials grew in sophistication and influence, the streptomycin trial continues to be referred to as ground breaking. The ethical advances in human protection include several milestones - Nuremberg Code, Declaration of Helsinki, Belmont Report, and 1996, International Conference on Harmonization Good Clinical Practice guidance. In parallel to ethical guidelines, clinical trials started to become embodied in regulation as government authorities began recognizing a need for controlling medical therapies in the early 20th century. As the scientific advances continue to occur, there will be new ethical and regulatory challenges requiring dynamic updates in ethical and legal framework of clinical trials.

  1. Essential Oil Content of the Rhizome of Curcuma purpurascens Bl. (Temu Tis) and Its Antiproliferative Effect on Selected Human Carcinoma Cell Lines

    PubMed Central

    Hong, Sok-Lai; Lee, Guan-Serm; Ahmed Hamdi, Omer Abdalla; Awang, Khalijah; Aznam Nugroho, Nurfina

    2014-01-01

    Curcuma purpurascens Bl., belonging to the Zingiberaceae family, is known as temu tis in Yogyakarta, Indonesia. In this study, the hydrodistilled dried ground rhizome oil was investigated for its chemical content and antiproliferative activity against selected human carcinoma cell lines (MCF7, Ca Ski, A549, HT29, and HCT116) and a normal human lung fibroblast cell line (MRC5). Results from GC-MS and GC-FID analysis of the rhizome oil of temu tis showed turmerone as the major component, followed by germacrone, ar-turmerone, germacrene-B, and curlone. The rhizome oil of temu tis exhibited strong cytotoxicity against HT29 cells (IC50 value of 4.9 ± 0.4 μg/mL), weak cytotoxicity against A549, Ca Ski, and HCT116 cells (with IC50 values of 46.3 ± 0.7, 32.5 ± 1.1, and 35.0 ± 0.3 μg/mL, resp.), and no inhibitory effect against MCF7 cells. It exhibited mild cytotoxicity against a noncancerous human lung fibroblast cell line (MRC5), with an IC50 value of 25.2 ± 2.7 μg/mL. This is the first report on the chemical composition of this rhizome's oil and its selective antiproliferative effect on HT29. The obtained data provided a basis for further investigation of the mode of cell death. PMID:25177723

  2. Space-Time Coded MC-CDMA: Blind Channel Estimation, Identifiability, and Receiver Design

    NASA Astrophysics Data System (ADS)

    Sun, Wei; Li, Hongbin

    2003-12-01

    Integrating the strengths of multicarrier (MC) modulation and code division multiple access (CDMA), MC-CDMA systems are of great interest for future broadband transmissions. This paper considers the problem of channel identification and signal combining/detection schemes for MC-CDMA systems equipped with multiple transmit antennas and space-time (ST) coding. In particular, a subspace based blind channel identification algorithm is presented. Identifiability conditions are examined and specified which guarantee unique and perfect (up to a scalar) channel estimation when knowledge of the noise subspace is available. Several popular single-user based signal combining schemes, namely the maximum ratio combining (MRC) and the equal gain combining (EGC), which are often utilized in conventional single-transmit-antenna based MC-CDMA systems, are extended to the current ST-coded MC-CDMA (STC-MC-CDMA) system to perform joint combining and decoding. In addition, a linear multiuser minimum mean-squared error (MMSE) detection scheme is also presented, which is shown to outperform the MRC and EGC at some increased computational complexity. Numerical examples are presented to evaluate and compare the proposed channel identification and signal detection/combining techniques.

  3. Using Mars Rover Missions as a Vehicle for Introducing Space Science and Engineering in Grades 3-8

    NASA Astrophysics Data System (ADS)

    Bering, Edgar A.; Slagle, Elana M.; Nieser, Kenneth; Carlson, Coleen; Kapral, Andrew J.; Jacobs, Laura A.

    2014-11-01

    The Mars Rover Celebration and Mars Rover Curriculum (MRC) for grades 3-8 are centered around an open-ended, student-led collaborative project to design a mission to Mars. This curriculum incorporates up-to-date SMD education resources and science and mission data relating to NASA’s explorations of Mars. The MRC focuses on the adventure of learning and discovery, asking participating teams to propose their own scientific mission to Mars, design a rover to carry it out, and present a mock-up at an open house. The curriculum is structured to be inquiry-based throughout. The “students choose the mission” structure is highly engaging. The latter half of the curriculum presents the Engineering Design Process and walks the students through the steps of designing and engineering a spacecraft/rover to meet the mission objectives chosen by the students. Students are introduced to engineering using the design-project approach. The six-week project period culminates in a public celebration at which students present their missions to members of the community including undergraduate and graduate students in science, engineering, and education fields; university faculty in these fields; and professionals from associated industries.

  4. Using Space Missions as a Vehicle for Introducing Engineering Education in Grades 3-8

    NASA Astrophysics Data System (ADS)

    Bering, E. A., III; Slagle, E. M.; Nieser, K.; Carlson, C.; Kapral, A. J.; Jacobs, L. T.

    2014-12-01

    The Mars Rover Celebration and Mars Rover Curriculum (MRC) for grades 3-8 are centered around an open-ended, student-led collaborative project to design a mission to Mars. This curriculum incorporates up-to-date SMD education resources and science and mission data relating to NASA's explorations of Mars. The MRC focuses on the adventure of learning and discovery, asking participating teams to propose their own scientific mission to Mars, design a rover to carry it out, and present a mock-up at an open house. The curriculum is structured to be inquiry-based throughout. The "students choose the mission" structure is highly engaging. The latter half of the curriculum presents the Engineering Design Process and walks the students through the steps of designing and engineering a spacecraft/rover to meet the mission objectives chosen by the students. Students are introduced to engineering using the design-project approach. The six-week project period culminates in a public celebration at which students present their missions to members of the community including undergraduate and graduate students in science, engineering, and education fields; university faculty in these fields; and professionals from associated industries.

  5. Connective tissue growth factor stimulates the proliferation, migration and differentiation of lung fibroblasts during paraquat-induced pulmonary fibrosis.

    PubMed

    Yang, Zhizhou; Sun, Zhaorui; Liu, Hongmei; Ren, Yi; Shao, Danbing; Zhang, Wei; Lin, Jinfeng; Wolfram, Joy; Wang, Feng; Nie, Shinan

    2015-07-01

    It is well established that paraquat (PQ) poisoning can cause severe lung injury during the early stages of exposure, finally leading to irreversible pulmonary fibrosis. Connective tissue growth factor (CTGF) is an essential growth factor that is involved in tissue repair and pulmonary fibrogenesis. In the present study, the role of CTGF was examined in a rat model of pulmonary fibrosis induced by PQ poisoning. Histological examination revealed interstitial edema and extensive cellular thickening of interalveolar septa at the early stages of poisoning. At 2 weeks after PQ administration, lung tissue sections exhibited a marked thickening of the alveolar walls with an accumulation of interstitial cells with a fibroblastic appearance. Masson's trichrome staining revealed a patchy distribution of collagen deposition, indicating pulmonary fibrogenesis. Western blot analysis and immunohistochemical staining of tissue samples demonstrated that CTGF expression was significantly upregulated in the PQ-treated group. Similarly, PQ treatment of MRC-5 human lung fibroblast cells caused an increase in CTGF in a dose-dependent manner. Furthermore, the addition of CTGF to MRC-5 cells triggered cellular proliferation and migration. In addition, CTGF induced the differentiation of fibroblasts to myofibroblasts, as was evident from increased expression of α-smooth muscle actin (α-SMA) and collagen. These findings demonstrate that PQ causes increased CTGF expression, which triggers proliferation, migration and differentiation of lung fibroblasts. Therefore, CTGF may be important in PQ-induced pulmonary fibrogenesis, rendering this growth factor a potential pharmacological target for reducing lung injury.

  6. The impairment of HCCS leads to MLS syndrome by activating a non-canonical cell death pathway in the brain and eyes

    PubMed Central

    Indrieri, Alessia; Conte, Ivan; Chesi, Giancarlo; Romano, Alessia; Quartararo, Jade; Tatè, Rosarita; Ghezzi, Daniele; Zeviani, Massimo; Goffrini, Paola; Ferrero, Ileana; Bovolenta, Paola; Franco, Brunella

    2013-01-01

    Mitochondrial-dependent (intrinsic) programmed cell death (PCD) is an essential homoeostatic mechanism that selects bioenergetically proficient cells suitable for tissue/organ development. However, the link between mitochondrial dysfunction, intrinsic apoptosis and developmental anomalies has not been demonstrated to date. Now we provide the evidence that non-canonical mitochondrial-dependent apoptosis explains the phenotype of microphthalmia with linear skin lesions (MLS), an X-linked developmental disorder caused by mutations in the holo-cytochrome c-type synthase (HCCS) gene. By taking advantage of a medaka model that recapitulates the MLS phenotype we demonstrate that downregulation of hccs, an essential player of the mitochondrial respiratory chain (MRC), causes increased cell death via an apoptosome-independent caspase-9 activation in brain and eyes. We also show that the unconventional activation of caspase-9 occurs in the mitochondria and is triggered by MRC impairment and overproduction of reactive oxygen species (ROS). We thus propose that HCCS plays a key role in central nervous system (CNS) development by modulating a novel non-canonical start-up of cell death and provide the first experimental evidence for a mechanistic link between mitochondrial dysfunction, intrinsic apoptosis and developmental disorders. PMID:23239471

  7. Comparison between impairment and disability scales in immune-mediated polyneuropathies.

    PubMed

    Merkies, Ingemar S J; Schmitz, Paul I M; Van Der Meché, Frans G A; Van Doorn, Pieter A

    2003-07-01

    The ability of a scale to detect clinical relevant changes over time, i.e., its "responsiveness," may help clinicians to choose among valid and reliable measures. Therefore, we investigated the responsiveness' rank ordering (best to worse) of six selected valid and reliable scales, namely the Medical Research Council (MRC)-sumscore, sensory-sumscore, grip-strength (Vigorimeter), nine-hole peg, ten-meters walking, and a disability-sumscore, in immune-mediated polyneuropathies. Patients with newly diagnosed Guillain-Barré syndrome (n = 7) or chronic inflammatory demyelinating polyneuropathy (n = 13) were examined over 52 weeks. Responsiveness of each scale was measured using different methods (effect-size, standardized response mean score, Wilcoxon matched-pairs signed-rank, and a newly devised Schmitz's distribution-free responsiveness score), and the obtained scores in each method were plotted against the follow-up period, thus allowing area-under-the-curve calculations (higher area-under-the-curve indicating better responsiveness). Also, longitudinal correlations were performed between the scales' values and patients' own clinical judgments (deteriorated, unchanged, improved) (higher correlation = better responsiveness). A consistent rank ordering was observed in each technique with the disability-sumscore, MRC-sumscore, and Vigorimeter being among the best responsive scales. Hence, the primary use of these measures is suggested in studies of immune-mediated polyneuropathies. PMID:12811779

  8. Detergent-resistant membrane microdomains facilitate Ib oligomer formation and biological activity of Clostridium perfringens iota-toxin.

    PubMed

    Hale, Martha L; Marvaud, Jean-Christophe; Popoff, Michel R; Stiles, Bradley G

    2004-04-01

    Clostridium perfringens iota-toxin consists of two separate proteins identified as a cell binding protein, iota b (Ib), which forms high-molecular-weight complexes on cells generating Na(+)/K(+)-permeable pores through which iota a (Ia), an ADP-ribosyltransferase, presumably enters the cytosol. Identity of the cell receptor and membrane domains involved in Ib binding, oligomer formation, and internalization is currently unknown. In this study, Vero (toxin-sensitive) and MRC-5 (toxin-resistant) cells were incubated with Ib, after which detergent-resistant membrane microdomains (DRMs) were extracted with cold Triton X-100. Western blotting revealed that Ib oligomers localized in DRMs extracted from Vero, but not MRC-5, cells while monomeric Ib was detected in the detergent-soluble fractions of both cell types. The Ib protoxin, previously shown to bind Vero cells but not form oligomers or induce cytotoxicity, was detected only in the soluble fractions. Vero cells pretreated with phosphatidylinositol-specific phospholipase C before addition of Ib indicated that glycosylphosphatidyl inositol-anchored proteins were minimally involved in Ib binding or oligomer formation. While pretreatment of Vero cells with filipin (which sequesters cholesterol) had no effect, methyl-beta-cyclodextrin (which extracts cholesterol) reduced Ib binding and oligomer formation and delayed iota-toxin cytotoxicity. These studies showed that iota-toxin exploits DRMs for oligomer formation to intoxicate cells.

  9. The general population cohort in rural south-western Uganda: a platform for communicable and non-communicable disease studies

    PubMed Central

    Asiki, Gershim; Murphy, Georgina; Nakiyingi-Miiro, Jessica; Seeley, Janet; Nsubuga, Rebecca N; Karabarinde, Alex; Waswa, Laban; Biraro, Sam; Kasamba, Ivan; Pomilla, Cristina; Maher, Dermot; Young, Elizabeth H; Kamali, Anatoli; Sandhu, Manjinder S

    2013-01-01

    The General Population Cohort (GPC) was set up in 1989 to examine trends in HIV prevalence and incidence, and their determinants in rural south-western Uganda. Recently, the research questions have included the epidemiology and genetics of communicable and non-communicable diseases (NCDs) to address the limited data on the burden and risk factors for NCDs in sub-Saharan Africa. The cohort comprises all residents (52% aged ≥13years, men and women in equal proportions) within one-half of a rural sub-county, residing in scattered houses, and largely farmers of three major ethnic groups. Data collected through annual surveys include; mapping for spatial analysis and participant location; census for individual socio-demographic and household socioeconomic status assessment; and a medical survey for health, lifestyle and biophysical and blood measurements to ascertain disease outcomes and risk factors for selected participants. This cohort offers a rich platform to investigate the interplay between communicable diseases and NCDs. There is robust infrastructure for data management, sample processing and storage, and diverse expertise in epidemiology, social and basic sciences. For any data access enquiries you may contact the director, MRC/UVRI, Uganda Research Unit on AIDS by email to mrc@mrcuganda.org or the corresponding author. PMID:23364209

  10. Recombinant growth hormone treatment of amyotrophic lateral sclerosis.

    PubMed

    Smith, R A; Melmed, S; Sherman, B; Frane, J; Munsat, T L; Festoff, B W

    1993-06-01

    Based on the known trophic effects of growth hormone (GH) on nerve and muscle 75 patients with ALS were treated for up to 18 months with synthetic human growth hormone (Protropin) or a placebo. The course of ALS was assessed serially using a quantitative (TQNE) neuromuscular and manual exam (MRC) and laboratory chemistries. Average insulin-related growth factor (IGF-I) values increased from 1.2 to 2.3 U/mL in the treated group. Surprisingly, serum insulin levels did not increase. Hyperglycemia was noted in only 2 patients of the 38 patients receiving hGH, and this resolved with cessation of treatment. Over the 12 months of treatment there were 11 deaths (6 controls, 5 treated). Survival analysis, performed approximately 12 months following cessation of treatment, did not reveal a difference between the treatment and placebo group. The TQNE scores declined inexorably in both the control and treated group. Retrospective analysis of the TQNE data indicated a poor prognosis for patients who lost arm strength early. A correlation between the TQNE and MRC scores was evident at early stages of motor unit loss, less so when muscle weakness was advanced. PMID:8502260

  11. Genomic instability of gold nanoparticle treated human lung fibroblast cells.

    PubMed

    Li, Jasmine J; Lo, Soo-Ling; Ng, Cheng-Teng; Gurung, Resham Lal; Hartono, Deny; Hande, Manoor Prakash; Ong, Choon-Nam; Bay, Boon-Huat; Yung, Lin-Yue Lanry

    2011-08-01

    Gold nanoparticles (AuNPs) are one of the most versatile and widely researched materials for novel biomedical applications. However, the current knowledge in their toxicological profile is still incomplete and many on-going investigations aim to understand the potential adverse effects in human body. Here, we employed two dimensional gel electrophoresis to perform a comparative proteomic analysis of AuNP treated MRC-5 lung fibroblast cells. In our findings, we identified 16 proteins that were differentially expressed in MRC-5 lung fibroblasts following exposure to AuNPs. Their expression levels were also verified by western blotting and real time RT-PCR analysis. Of interest was the difference in the oxidative stress related proteins (NADH ubiquinone oxidoreductase (NDUFS1), protein disulfide isomerase associate 3 (PDIA3), heterogeneous nuclear ribonucleus protein C1/C2 (hnRNP C1/C2) and thioredoxin-like protein 1 (TXNL1)) as well as proteins associated with cell cycle regulation, cytoskeleton and DNA repair (heterogeneous nuclear ribonucleus protein C1/C2 (hnRNP C1/C2) and Secernin-1 (SCN1)). This finding is consistent with the genotoxicity observed in the AuNP treated lung fibroblasts. These results suggest that AuNP treatment can induce oxidative stress-mediated genomic instability.

  12. PL37: a new hope in the treatment of painful diabetic neuropathy?

    PubMed

    Tesfaye, Solomon

    2016-04-01

    Solomon Tesfaye speaks to Nick Ward, Commissioning Editor: Solomon Tesfaye, MB ChB, MD, FRCP, speaks about PL37; the first orally administered dual inhibitor of enkephalinases and its potential role in the treatment of painful diabetic neuropathy. Solomon Tesfaye is a Consultant Physician/Endocrinologist at Sheffield Teaching Hospitals and Honorary Professor of Diabetic Medicine at the University of Sheffield. His research projects include the epidemiology, risk factors, pathogenesis, CNS involvement and treatment of diabetic neuropathy and neuropathic pain. He was awarded the Prestigious Camillo Golgi Prize of the European Association for the Study of Diabetes (EASD) in 2014 for major scientific contributions in diabetic neuropathy. He has had international leadership roles including chairmanship of the International Expert Group on Diabetic Neuropathy, and of NEURODIAB (2006-2009). He is also a member of the Science and Research Committee of Diabetes UK; a review panel member for the MRC, a Board Member of the Global Quantitative Sensation Testing Society; a member of the Advisory Council of the Neuropathy Trust; and Secretary of International Insulin Foundation. He has served as a member of the MRC, JDRF, NIDDK and UK NIHR scientific review panels and as a member of a Diabetes and Neuropathic Pain Review Group for NICE.

  13. Implementation and 8-year follow-up of an uninterrupted oxygen supply system in a hospital in The Gambia

    PubMed Central

    Light, J. D.; Ebonyi, A. O.; N'Jai, P. C.; Ideh, R. C.; Ebruke, B. E.; Nyassi, E.; Peel, D.

    2016-01-01

    SUMMARY SETTING: A 42-bed hospital operated by the Medical Research Council (MRC) Unit in The Gambia. OBJECTIVE: To devise, test and evaluate a cost-efficient uninterrupted oxygen system in the MRC Hospital. DESIGN: Oxygen cylinders were replaced with oxygen concentrators as the primary source of oxygen. An uninterruptable power supply (UPS) ensured continuity of power. Hospital staff were trained on the use of the new system. Eight years post-installation, an analysis of concentrator maintenance needs and costs was conducted and user feedback obtained to assess the success of the system. RESULTS: The new system saved at least 51% of oxygen supply costs compared to cylinders, with savings likely to have been far greater due to cylinder leakages. Users indicated that the system is easier to use and more reliable, although technical support and staff training are still needed. CONCLUSION: Oxygen concentrators offer long-term cost savings and an improved user experience compared to cylinders; however, some technical support and maintenance are needed to upkeep the system. A UPS dedicated to oxygen concentrators is an appropriate solution for settings where power interruptions are frequent but short in duration. This approach can be a model for health systems in settings with similar infrastructure. PMID:27393551

  14. Safety and efficacy of strength training in patients with sporadic inclusion body myositis.

    PubMed

    Spector, S A; Lemmer, J T; Koffman, B M; Fleisher, T A; Feuerstein, I M; Hurley, B F; Dalakas, M C

    1997-10-01

    We studied the effects of a 12-week progressive resistance strength training program in weakened muscles of 5 patients with sporadic inclusion body myositis (IBM). Strength was evaluated with Medical Research Council (MRC) scale ratings and quantitative isometric and dynamic tests. Changes in serum creatine kinase (CK), lymphocyte subpopulations, muscle size (determined by magnetic resonance imaging), and histology in repeated muscle biopsies were examined before and after training. After 12 weeks, the values of repetition maximum improved in the least weakened muscles, 25-120% from baseline. This dynamic effect was not captured by MRC or isometric muscle strength measurements. Serum CK, B cells, T-cell subsets, and NK cells remained unchanged. Repeat muscle biopsies did not reveal changes in the number and degree of degenerating fibers or inflammation. The size of the trained muscles did not change. We conclude that a supervised progressive resistance training program in IBM patients can lead to gains in dynamic strength of the least weak muscles without causing muscle fatigue and muscle injury or serological, histological, and immunological abnormalities. Even though the functional significance of these gains is unclear, this treatment modality is a safe and perhaps overlooked means of rehabilitation of IBM patients. PMID:9324080

  15. The Continuing Challenges of Translational Research: Clinician-Scientists' Perspective

    PubMed Central

    Homer-Vanniasinkam, Shervanthi; Tsui, Janice

    2012-01-01

    Over the last twenty years, revolutionary advances in biomedicine including gene therapy, stem cell research, proteomics, genomics and nanotechnology have highlighted the progressive need to restructure traditional approaches to basic and clinical research in order to facilitate the rapid, efficient integration and translation of these new technologies into novel effective therapeutics. Over the past ten years, funding bodies in the USA and UK such as the National Institutes of Health (NIH) and the Medical Research Council (MRC) have been driving translational research by defining and tackling the hurdles but more still remains to be achieved. This article discusses the ongoing challenges translational researchers face and outlines recent initiatives to tackle these including the new changes to translational funding schemes proposed by the NIH and the MRC and the launch of the “European Advanced Translational Research InfraStructure in Medicine” (EATRIS). It is anticipated that initiatives such as these will not only strengthen translational biomedical research programmes already initiated but should lead to rapid benefits to patients and society. PMID:23050194

  16. Chemical Characterization and Cytotoxic Activity of Blueberry Extracts (cv. Misty) Cultivated in Brazil.

    PubMed

    Massarotto, Giovana; Barcellos, Thiago; Garcia, Charlene Silvestrin Celi; Brandalize, Ana Paula Carneiro; Moura, Sidnei; Schwambach, Joséli; Henriques, João Antonio Pêgas; Roesch-Ely, Mariana

    2016-08-01

    Vaccinium corymbosum (L.) varieties cultivation is relatively recent in Brazil, but its production has been intensified given its good adaptability to the Southern Brazil climate. Blueberries are a rich source of phenolic compounds and contain significant levels of anthocyanins, flavonols, chlorogenic acids, and procyanidins, which lead to different biological activities. Chemical identification of skin and whole hydroalcoholic blueberry extracts (ExtSB and ExtWB) revealed the presence of anthocyanins concentrated in the skin and others chemicals compounds as quercetin glycosides, proanthocyanins dimers, citric, and chlorogenic acid in the pulp. Selectivity for tumor cell lines (Hep-2, HeLa, HT-29) using ExtSB and ExtWB extracts was observed through MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay after 24 h of treatment when compared to nontumor cells (MRC-5). Morphological changes and late stages of apoptotic and necrosis process were seen in HT-29 cell line after ExtWB treatment, compared to nontumor cell line MRC-5. These results are in agreement with other studies that indicate the activity of compounds such as anthocyanins and other molecules found in Southern Highbush blueberry variety, attributed to promote beneficial effects on health that may respond as cytotoxic natural agent and contribute to cancer treatment. PMID:27411085

  17. The Study of Environment on Aboriginal Resilience and Child Health (SEARCH): a long-term platform for closing the gap.

    PubMed

    Wright, Darryl; Gordon, Raylene; Carr, Darren; Craig, Jonathan C; Banks, Emily; Muthayya, Sumithra; Wutzke, Sonia; Eades, Sandra J; Redman, Sally

    2016-01-01

    The full potential for research to improve Aboriginal health has not yet been realised. This paper describes an established long-term action partnership between Aboriginal Community Controlled Health Services (ACCHSs), the Aboriginal Health and Medical Research Council of New South Wales (AH&MRC), researchers and the Sax Institute, which is committed to using high-quality data to bring about health improvements through better services, policies and programs. The ACCHSs, in particular, have ensured that the driving purpose of the research conducted is to stimulate action to improve health for urban Aboriginal children and their families. This partnership established a cohort study of 1600 urban Aboriginal children and their caregivers, known as SEARCH (the Study of Environment on Aboriginal Resilience and Child Health), which is now having significant impacts on health, services and programs for urban Aboriginal children and their families. This paper describes some examples of the impacts of SEARCH, and reflects on the ways of working that have enabled these changes to occur, such as strong governance, a focus on improved health, AH&MRC and ACCHS leadership, and strategies to support the ACCHS use of data and to build Aboriginal capacity. PMID:27421347

  18. Fasting Glucose Levels Correlate with Disease Severity of Guillain-Barré Syndrome

    PubMed Central

    Wang, Ying; Guan, Yun; Press, Rayomand; Zhu, Jie; Zhang, Hong-Liang

    2015-01-01

    Objective A potential association between diabetes and Guillain-Barré syndrome (GBS) has been indicated by a few case studies. We retrospectively analyzed the clinical features of a large cohort of GBS patients to explore the relationship between the level of fasting plasma glucose (FPG) obtained in the acute phase at admission and the severity of GBS. Methods Three hundred and four GBS patients were divided into two groups, one with normal FPG and the other with high FPG levels according to the international standards of FPG. Results The GBS disability scale score was positively, the Medical Research Council (MRC) sum score was negatively correlated to the level of FPG, but not to blood HBA1c or CSF glucose concentrations. A relatively higher FPG level was observed in older and younger GBS patients, and more often in those with cranial nerve involvement, autonomic deficit, dyspnea and ventilator dependence than in patients without these clinical characteristics. Importantly, higher levels of FPG at admission were associated with poorer short-term prognosis measured by the MRC sum score and the GBS disability scale at discharge. Conclusions Our data demonstrates that FPG in the acute phase of GBS correlates with the severity of GBS and may predict the short-term prognosis of GBS. PMID:26684748

  19. Morphological and ultrastructural characterization of ionoregulatory cells in the teleost Oreochromis niloticus following salinity challenge combining complementary confocal scanning laser microscopy and transmission electron microscopy using a novel prefixation immunogold labeling technique.

    PubMed

    Fridman, Sophie; Rana, Krishen J; Bron, James E

    2013-10-01

    Aspects of ionoregulatory or mitochondria-rich cell (MRC) differentiation and adaptation in Nile tilapia yolk-sac larvae following transfer from freshwater to elevated salinities, that is, 12.5 and 20 ppt are described. Investigations using immunohistochemistry on whole-mount Nile tilapia larvae using anti- Na⁺/K⁺-ATPase as a primary antibody and Fluoronanogold™ (Nanoprobes) as a secondary immunoprobe allowed fluorescent labeling with the high resolution of confocal scanning laser microscopy combined with the detection of immunolabeled target molecules at an ultrastructural level using transmission electron microscopy (TEM). It reports, for the first time, various developmental stages of MRCs within the epithelial layer of the tail of yolk-sac larvae, corresponding to immature, developing, and mature MRCs, identifiable by their own characteristic ultrastructure and form. Following transfer to hyperosmotic salinities the density of immunogold particles and well as the intricacy of the tubular system appeared to increase. In addition, complementary confocal scanning laser microscopy allowed identification of immunopositive ramifying extensions that appeared to emanate from the basolateral portion of the cell that appeared to be correlated with the localization of subsurface tubular areas displaying immunogold labeled Na⁺/K⁺-ATPase. This integrated approach describes a reliable and repeatable prefixation immunogold labeling technique allowing precise visualization of NaK within target cells combined with a 3D imaging that offers valuable insights into MRC dynamics at an ultrastructural level.

  20. Synthesis, antiproliferative and antifungal activities of 1,2,3-triazole-substituted carnosic Acid and carnosol derivatives.

    PubMed

    Pertino, Mariano Walter; Theoduloz, Cristina; Butassi, Estefania; Zacchino, Susana; Schmeda-Hirschmann, Guillermo

    2015-01-01

    Abietane diterpenes exhibit an array of interesting biological activities, which have generated significant interest among the pharmacological community. Starting from the abietane diterpenes carnosic acid and carnosol, twenty four new triazole derivatives were synthesized using click chemistry. The compounds differ in the length of the linker and the substituent on the triazole moiety. The compounds were assessed as antiproliferative and antifungal agents. The antiproliferative activity was determined on normal lung fibroblasts (MRC-5), gastric epithelial adenocarcinoma (AGS), lung cancer (SK-MES-1) and bladder carcinoma (J82) cells while the antifungal activity was assessed against Candida albicans ATCC 10231 and Cryptococcus neoformans ATCC 32264. The carnosic acid γ-lactone derivatives 1-3 were the most active antiproliferative compounds of the series, with IC50 values in the range of 43.4-46.9 μM and 39.2-48.9 μM for MRC-5 and AGS cells, respectively. Regarding antifungal activity, C. neoformans was the most sensitive fungus, with nine compounds inhibiting more than 50% of its fungal growth at concentrations ≤250 µg∙mL-1. Compound 22, possessing a p-Br-benzyl substituent on the triazole ring, showed the best activity (91% growth inhibition) at 250 µg∙mL-1 In turn, six compounds inhibited 50% C. albicans growth at concentrations lower than 250 µg∙mL-1. PMID:26007173

  1. Multiple-methods investigation of recharge at a humid-region fractured rock site, Pennsylvania, USA

    USGS Publications Warehouse

    Heppner, C.S.; Nimmo, J.R.; Folmar, G.J.; Gburek, W.J.; Risser, D.W.

    2007-01-01

    Lysimeter-percolate and well-hydrograph analyses were combined to evaluate recharge for the Masser Recharge Site (central Pennsylvania, USA). In humid regions, aquifer recharge through an unconfined low-porosity fractured-rock aquifer can cause large magnitude water-table fluctuations over short time scales. The unsaturated hydraulic characteristics of the subsurface porous media control the magnitude and timing of these fluctuations. Data from multiple sets of lysimeters at the site show a highly seasonal pattern of percolate and exhibit variability due to both installation factors and hydraulic property heterogeneity. Individual event analysis of well hydrograph data reveals the primary influences on water-table response, namely rainfall depth, rainfall intensity, and initial water-table depth. Spatial and seasonal variability in well response is also evident. A new approach for calculating recharge from continuous water-table elevation records using a master recession curve (MRC) is demonstrated. The recharge estimated by the MRC approach when assuming a constant specific yield is seasonal to a lesser degree than the recharge estimate resulting from the lysimeter analysis. Partial reconciliation of the two recharge estimates is achieved by considering a conceptual model of flow processes in the highly-heterogeneous underlying fractured porous medium. ?? Springer-Verlag 2007.

  2. PBP1a/LpoA but not PBP1b/LpoB are involved in regulation of the major β-lactamase gene blaA in Shewanella oneidensis.

    PubMed

    Yin, Jianhua; Sun, Yiyang; Mao, Yinting; Jin, Miao; Gao, Haichun

    2015-01-01

    β-Lactamase production is one of the most important strategies for Gram-negative bacteria to combat β-lactam antibiotics. Studies of the regulation of β-lactamase expression have largely been focused on the class C β-lactamase AmpC, whose induction by β-lactams requires LysR-type regulator AmpR and permease AmpG-dependent peptidoglycan recycling intermediates. In Shewanella, which is ubiquitous in aquatic environments and is a reservoir for antibiotic resistance, production of the class D β-lactamase BlaA confers bacteria with natural resistance to many β-lactams. Expression of the blaA gene in the genus representative Shewanella oneidensis is distinct from the AmpC paradigm because of the lack of an AmpR homologue and the presence of an additional AmpG-independent regulatory pathway. In this study, using transposon mutagenesis, we identify proteins that are involved in blaA regulation. Inactivation of mrcA and lpoA, which encode penicillin binding protein 1a (PBP1a) and its lipoprotein cofactor, LpoA, respectively, drastically enhances blaA expression in the absence of β-lactams. Although PBP1b and its cognate, LpoB, also exist in S. oneidensis, their roles in blaA induction are dispensable. We further show that the mrcA-mediated blaA expression is independent of AmpG.

  3. Trimethylamine N-oxide metabolism by abundant marine heterotrophic bacteria

    PubMed Central

    Lidbury, Ian; Murrell, J. Colin; Chen, Yin

    2014-01-01

    Trimethylamine N-oxide (TMAO) is a common osmolyte found in a variety of marine biota and has been detected at nanomolar concentrations in oceanic surface waters. TMAO can serve as an important nutrient for ecologically important marine heterotrophic bacteria, particularly the SAR11 clade and marine Roseobacter clade (MRC). However, the enzymes responsible for TMAO catabolism and the membrane transporter required for TMAO uptake into microbial cells have yet to be identified. We show here that the enzyme TMAO demethylase (Tdm) catalyzes the first step in TMAO degradation. This enzyme represents a large group of proteins with an uncharacterized domain (DUF1989). The function of TMAO demethylase in a representative from the SAR11 clade (strain HIMB59) and in a representative of the MRC (Ruegeria pomeroyi DSS-3) was confirmed by heterologous expression of tdm (the gene encoding Tdm) in Escherichia coli. In R. pomeroyi, mutagenesis experiments confirmed that tdm is essential for growth on TMAO. We also identified a unique ATP-binding cassette transporter (TmoXWV) found in a variety of marine bacteria and experimentally confirmed its specificity for TMAO through marker exchange mutagenesis and lacZ reporter assays of the promoter for genes encoding this transporter. Both Tdm and TmoXWV are particularly abundant in natural seawater assemblages and actively expressed, as indicated by a number of recent metatranscriptomic and metaproteomic studies. These data suggest that TMAO represents a significant, yet overlooked, nutrient for marine bacteria. PMID:24550299

  4. Diversity-Enabled and Power-Efficient Transceiver Designs for Peak-Power-Limited SIMO-OFDM Systems

    NASA Astrophysics Data System (ADS)

    Liu, Qijia; Baxley, RobertJ; Ma, Xiaoli; Zhou, G. Tong

    2010-12-01

    Orthogonal frequency division multiplexing (OFDM) has been widely adopted for high data rate wireless transmissions. By deploying multiple receiving antennas, single-input multiple-output- (SIMO-) OFDM can further enhance the performance with spatial diversity. However, due to the large dynamic range of OFDM signals and the nonlinear nature of analog components, it is pragmatic to model the transmitter with a peak-power constraint. A natural question to ask is whether SIMO-OFDM transmissions can still enjoy the antenna diversity in this case. In this paper, the effect of the peak-power limit on the error performance of uncoded SIMO-OFDM systems is studied. In the case that the receiver has no information about the transmitter nonlinearity, we show that full antenna diversity can still be collected by carefully designing the transmitters, while the receiver performs a maximum ratio combining (MRC) method which is implemented the same as that in the average power constrained case. On the other hand, when the receiver has perfect knowledge of the peak-power-limited transmitter nonlinearity, zero-forcing (ZF) equalizer is able to collect full antenna diversity. In addition, an iterative method on joint MRC and clipping mitigation is proposed to achieve high performance with low complexity.

  5. Mitochondrial DNA disturbances and deregulated expression of oxidative phosphorylation and mitochondrial fusion proteins in sporadic inclusion body myositis.

    PubMed

    Catalán-García, Marc; Garrabou, Glòria; Morén, Constanza; Guitart-Mampel, Mariona; Hernando, Adriana; Díaz-Ramos, Àngels; González-Casacuberta, Ingrid; Juárez, Diana-Luz; Bañó, Maria; Enrich-Bengoa, Jennifer; Emperador, Sonia; Milisenda, José César; Moreno, Pedro; Tobías, Ester; Zorzano, Antonio; Montoya, Julio; Cardellach, Francesc; Grau, Josep Maria

    2016-10-01

    Sporadic inclusion body myositis (sIBM) is one of the most common myopathies in elderly people. Mitochondrial abnormalities at the histological level are present in these patients. We hypothesize that mitochondrial dysfunction may play a role in disease aetiology. We took the following measurements of muscle and peripheral blood mononuclear cells (PBMCs) from 30 sIBM patients and 38 age- and gender-paired controls: mitochondrial DNA (mtDNA) deletions, amount of mtDNA and mtRNA, mitochondrial protein synthesis, mitochondrial respiratory chain (MRC) complex I and IV enzymatic activity, mitochondrial mass, oxidative stress and mitochondrial dynamics (mitofusin 2 and optic atrophy 1 levels). Depletion of mtDNA was present in muscle from sIBM patients and PBMCs showed deregulated expression of mitochondrial proteins in oxidative phosphorylation. MRC complex IV/citrate synthase activity was significantly decreased in both tissues and mitochondrial dynamics were affected in muscle. Depletion of mtDNA was significantly more severe in patients with mtDNA deletions, which also presented deregulation of mitochondrial fusion proteins. Imbalance in mitochondrial dynamics in muscle was associated with increased mitochondrial genetic disturbances (both depletion and deletions), demonstrating that proper mitochondrial turnover is essential for mitochondrial homoeostasis and muscle function in these patients.

  6. IVIDIL experiment on the ISS. Measurement of transport coefficients in liquids.

    NASA Astrophysics Data System (ADS)

    Shevtsova, Valentina

    The purpose of the SODI-IVIDIL project is to measure thermal and isothermal diffusion coeffi-cients in binary liquids subjected to controlled vibration under different values of amplitude and frequency. There exist a number of numerical codes to assess for studying the effect of resid-ual gravity and vibration, but their reliability is difficult to assess due to lack of experimental investigations. The IVIDIL project should therefore provide reference data for the validation and testing of numerical codes. After more than 5 years ground based preparation the experiment IVIDIL (Influence of Vibra-tion on Diffusion in Liquids) has started on 5th October 2009 on the ISS. Totally 55 experimental runs were successfully finished by 20 January 2010 using ESA's SODI multi user facility. Each original run lasted 18 hours. Three International Teams are involved in the project. ULB (MRC, Belgium, led by V. Shevtsova); Russian team from Perm, ICMM UB RAS (led by T. Lyubimova) and team from Ryerson University (led by Z. Saghir), Ontario, Canada. The author, being a coordinator of the overall project, will present a general description of the experiment and outline some first results obtained by MRC, ULB researchers only, i.e. by A. Mialdun, D. Melnikov and Yu. Gaponenko.

  7. Data sharing in international transboundary contexts: The Vietnamese perspective on data sharing in the Lower Mekong Basin

    NASA Astrophysics Data System (ADS)

    Thu, Hang Ngo; Wehn, Uta

    2016-05-01

    Transboundary data sharing is widely recognised as a necessary element in the successful handling of water-related climate change issues, as it is a means towards integrated water resources management (IWRM). However, in practice it is often a challenge to achieve it. The Mekong River Commission (MRC), an inter-governmental agency established by Cambodia, Lao PDR, Thailand and Vietnam, has adopted IWRM in its water strategy plan in order to properly manage the transboundary waters of the Mekong River. In this context, data sharing procedures were institutionalised and have been officially implemented by the four member countries since 2001. This paper uses a systematic approach to identify the extent of data sharing and the factors influencing the willingness of key individuals in the Vietnam National Mekong Committee and its Primary Custodians to share data. We find that the initial objectives of the Procedures for Data and Information Exchange and Sharing (PDIES) have not been fully achieved and, further, that Vietnam has much to gain and little to lose by engaging in data sharing in the MRC context. The primary motivation for data sharing stems from the desire to protect national benefits and to prevent upstream countries from overexploiting the shared water resources. However, data sharing is hindered by a lack of national regulations in the Vietnam context concerning data sharing between state agencies and outdated information management systems.

  8. Experimental heat and mass transfer of the separated and coupled rotating desiccant wheel and heat wheel

    SciTech Connect

    Enteria, Napoleon; Yoshino, Hiroshi; Mochida, Akashi; Takaki, Rie; Satake, Akira; Yoshie, Ryuichiro; Mitamura, Tiruaki; Baba, Seizo

    2010-07-15

    The experimental evaluation of the separated and coupled rotating desiccant wheel and heat wheel is reported. The study aims to investigate the performance of the desiccant wheel and of the heat wheel both when operated separately and jointly. The performance evaluation of the desiccant wheel is based on its moisture removal capacity (MRC), moisture removal regeneration (MRR), and moisture mass balance (MMB). In addition, the study used the total energy balance (TEB), sensible coefficient of performance (COP{sub Sensible}), latent coefficient of performance (COP{sub Latent}) and, total coefficient of performance (COP{sub Total}). The performance of the heat wheel is based on its effectiveness. The COP{sub Sensible}, COP{sub Latent} and, COP{sub Total} are used in the performance evaluation of the coupled desiccant wheel and heat wheel. The general results of the study show that the MRC, MRR and MMB coupled with the TEB, COP{sub Latent}, COP{sub Sensible} and COP{sub Total} predict adequately the performance of the desiccant wheel. In addition, the coupled operation of the desiccant wheel and heat wheel, contributed to the reduction of the external thermal energy requirement for the regeneration of the desiccant wheel. This study can be applied in other researches seeking evaluation of the desiccant wheel, heat wheel, and their combined operation. Moreover, the data presented here are significant for the desiccant wheel benchmarking and for evaluation of the desiccant wheel models. (author)

  9. Purine catabolic pathway revealed by transcriptomics in the model marine bacterium Ruegeria pomeroyi DSS-3.

    PubMed

    Cunliffe, Michael

    2016-01-01

    Purines are nitrogen-rich compounds that are widely distributed in the marine environment and are an important component of the dissolved organic nitrogen (DON) pool. Even though purines have been shown to be degraded by bacterioplankton, the identities of marine bacteria capable of purine degradation and their underlying catabolic mechanisms are currently unknown. This study shows that Ruegeria pomeroyi, a model marine bacterium and Marine Roseobacter Clade (MRC) representative, utilizes xanthine as a source of carbon and nitrogen. The R. pomeroyi genome contains putative genes that encode xanthine dehydrogenase (XDH), which is expressed during growth with xanthine. RNAseq-based analysis of the R. pomeroyi transcriptome revealed that the transcription of an XDH-initiated catabolic pathway is up-regulated during growth with xanthine, with transcription greatest when xanthine was the only available carbon source. The RNAseq-deduced pathway indicates that glyoxylate and ammonia are the key intermediates from xanthine degradation. Utilising a laboratory model, this study has identified the potential genes and catabolic pathway active during xanthine degradation. The ability of R. pomeroyi to utilize xanthine provides novel insights into the capabilities of the MRC that may contribute to their success in marine ecosystems and the potential biogeochemical importance of the group in processing DON.

  10. Real-life assessment of the multidimensional nature of dyspnoea in COPD outpatients.

    PubMed

    Morélot-Panzini, Capucine; Gilet, Hélène; Aguilaniu, Bernard; Devillier, Philippe; Didier, Alain; Perez, Thierry; Pignier, Christophe; Arnould, Benoit; Similowski, Thomas

    2016-06-01

    Dyspnoea is a prominent symptom of chronic obstructive pulmonary disease (COPD). Recent multidimensional dyspnoea questionnaires like the Multidimensional Dyspnea Profile (MDP) individualise the sensory and affective dimensions of dyspnoea. We tested the MDP in COPD outpatients based on the hypothesis that the importance of the affective dimension of dyspnoea would vary according to clinical characteristics.A multicentre, prospective, observational, real-life study was conducted in 276 patients. MDP data were compared across various categories of patients (modified Medical Research Council (mMRC) dyspnoea score, COPD Assessment Test (CAT) score, Global Initiative for Chronic Obstructive Lung Disease (GOLD) airflow obstruction categories, GOLD "ABCD" categories, and Hospital Anxiety and Depression Scale (HADS)). Univariate and multivariate regressions were conducted to explore factors influencing the affective dimension of dyspnoea. Cluster analysis was conducted to create homogeneous patient profiles.The MDP identified a more marked affective dimension of dyspnoea with more severe mMRC, CAT, 12-item Short-Form Health Survey mental component, airflow obstruction and HADS. Multivariate analysis identified airflow obstruction, depressive symptoms and physical activity as determinants of the affective dimension of dyspnoea. Patients clustered into an "elderly, ex-smoker, severe disease, no rehabilitation" group exhibited the most marked affective dimension of dyspnoea.An affective/emotional dimension of dyspnoea can be identified in routine clinical practice. It can contribute to the phenotypic description of patients. Studies are needed to determine whether targeted therapeutic interventions can be designed and whether they are useful.

  11. Cytotoxic activity of acetogenins and styryl lactones isolated from Goniothalamus undulatus Ridl. root extracts against a lung cancer cell line (COR-L23).

    PubMed

    Tantithanaporn, S; Wattanapiromsakul, C; Itharat, A; Keawpradub, N

    2011-04-15

    An investigation of the chemical constituents in a dichloromethnae extract of Goniothalamus undulatus root led to the isolation of three known styryl lactones (5-acetoxyisogoniothalamin oxide, O-acetylaltholactone and altholactone), and four known annonaceous acetogenins (annonacin, cis-annonacin, goniothalamicin and cis-goniothalamicin). These compounds were subjected to a sulphorhodamine B (SRB) cytotoxicity assay against human large cell lung carcinoma (COR-L23), and normal human fetal fibroblast (MRC-5), cell lines. The isolated acetogenins showed higher cytotoxic activity against COR-L23 compared to the styryl lactones, with IC₅₀ values in the range of 0.5-1.7 μM and 7.4-15.4 μM, respectively. A similar pattern of cytotoxicity was also observed against the other cell line (MRC-5); acetogenins IC₅₀ values were in the range of 11.8-31.4 μM, and those for styryl lactones were in the range of 48.7-102.8 μM. This is the first report of a bioassay-guided isolation of chemical constituents from G. undulatus and on cytotoxic studies of the isolated compounds using these particular lung cancer cell lines. PMID:21112751

  12. A Rare Complication of Herpes Zoster: Segmental Zoster Paresis

    PubMed Central

    Teo, Hooi Khee; Chawla, Mayank; Kaushik, Manish

    2016-01-01

    Herpes zoster is a common presentation in both the community and emergency department; however segmental zoster paresis is a rare complication that can lead to misdiagnosis. We present a case of a 74-year-old Indian gentleman with a background of well controlled diabetes mellitus, hypertension, and ischaemic heart disease who presented with sudden right lower limb weakness. This was preceded by a 5-day history of paraesthesia starting in the right foot and ascending up the right lower limb. On examination, there was a characteristic vesicular rash in the L2/3 region with MRC grading 3/5 in the right hip flexors. The rest of the neurological examination was unremarkable. MRI of the spine did not show any evidence of spinal disease. The patient was initiated on IV acyclovir with improvement of the lower limb weakness to MRC grading 5/5 as the vesicles improved. This is an interesting case as it highlights a rare presentation of zoster: segmental motor paresis that recovered fully with resolution of the rash. It shows the importance of recognizing motor neuropathy as a complication of shingles as it has a very good prognosis with most patients regaining full motor function of the affected limb with treatment. PMID:27313622

  13. Investigation of aromatase inhibitory activity of metal complexes of 8-hydroxyquinoline and uracil derivatives

    PubMed Central

    Prachayasittikul, Veda; Pingaew, Ratchanok; Nantasenamat, Chanin; Prachayasittikul, Supaluk; Ruchirawat, Somsak; Prachayasittikul, Virapong

    2014-01-01

    Purpose Estrogens play important roles in the pathogenesis and progression of breast cancer as well as estrogen-related diseases. Aromatase is a key enzyme in the rate-limiting step of estrogen production, in which its inhibition is one strategy for controlling estrogen levels to improve prognosis of estrogen-related cancers and diseases. Herein, a series of metal (Mn, Cu, and Ni) complexes of 8-hydroxyquinoline (8HQ) and uracil derivatives (4–9) were investigated for their aromatase inhibitory and cytotoxic activities. Methods The aromatase inhibition assay was performed according to a Gentest™ kit using CYP19 enzyme, wherein ketoconazole and letrozole were used as reference drugs. The cytotoxicity was tested on normal embryonic lung cells (MRC-5) using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Results Only Cu complexes (6 and 9) exhibited aromatase inhibitory effect with IC50 0.30 and 1.7 μM, respectively. Cytotoxicity test against MRC-5 cells showed that Mn and Cu complexes (5 and 6), as well as free ligand 8HQ, exhibited activity with IC50 range 0.74–6.27 μM. Conclusion Cu complexes (6 and 9) were found to act as a novel class of aromatase inhibitor. Our findings suggest that these 8HQ–Cu–uracil complexes are promising agents that could be potentially developed as a selective anticancer agent for breast cancer and other estrogen-related diseases. PMID:25152615

  14. Combination of spatial diversity and parallel decision feedback equalizer in a Single Input Multiple Output underwater acoustic communication system operating at very high frequencies

    NASA Astrophysics Data System (ADS)

    Skoro Kaskarovska, Violeta; Beaujean, Pierre-Philippe

    2013-05-01

    Single Input Multiple Output (SIMO) acoustic communication system using an adaptive spatial diversity combined with parallel Decision Feedback Equalizer (DFE) is presented in this document. The SIMO system operates at high frequencies with high data rate over a limited range (less than 200 m) in very shallow waters. The SIMO system consists of a single source transmitting Phase Shift Keying (PSK) messages modulated at 300 kHz and received by multiple receivers. In a first configuration, the symbols collected at each receiver are equalized using a decision feedback equalizer and combined using Maximum Ratio Combining (MRC). In a second configuration, the MRC outputs are used as decision symbols in the DFE. This second configuration is a form of turbo equalization: the process can be repeated over and over, leading to a better estimate of the received message as the number of iterations increases. The adaptive process of diversity is repeated until the best possible result is achieved or a predefined error criterion is met. Bit Error Rate (BER) and Signal-to-Noise-and-Interference Ratio (SNIR) are used as performance metrics of the acoustic channel. Experimental results using SIMO system with three, four or five receivers and pre-processed real recorded data demonstrate ability to improve the performance of the acoustic channel in challenging environments. Using received messages with non-zero BER, adaptive spatial diversity can achieve BER of 0% and increased SNIR of 3 dB with number of iterations depending on the number of receivers used.

  15. Plasmid partitioning systems of conjugative plasmids from Clostridium perfringens.

    PubMed

    Adams, Vicki; Watts, Thomas D; Bulach, Dieter M; Lyras, Dena; Rood, Julian I

    2015-07-01

    Many pathogenic strains of Clostridium perfringens carry several highly similar toxin or antibiotic resistance plasmids that have 35 to 40 kb of very closely related syntenous sequences, including regions that carry the genes encoding conjugative transfer, plasmid replication and plasmid maintenance functions. Key questions are how are these closely related plasmids stably maintained in the same cell and what is the basis for plasmid incompatibility in C. perfringens. Comparative analysis of the Rep proteins encoded by these plasmids suggested that this protein was not the basis for plasmid incompatibility since plasmids carried in a single strain often encoded an almost identical Rep protein. These plasmids all carried a similar, but not identical, parMRC plasmid partitioning locus. Phylogenetic analysis of the deduced ParM proteins revealed that these proteins could be divided into ten separate groups. Importantly, in every strain that carried more than one of these plasmids, the respective ParM proteins were from different phylogenetic groups. Similar observations were made from the analysis of phylogenetic trees of the ParR proteins and the parC loci. These findings provide evidence that the basis for plasmid incompatibility in the conjugative toxin and resistance plasmid family from C. perfringens resides in subtle differences in the parMRC plasmid partitioning loci carried by these plasmids.

  16. Unravelling the ‘Tangled Web’: Chemotherapy for Tuberculosis in Britain, 1940–701 The William Bynum Prize Essay

    PubMed Central

    Leeming-Latham, Clare

    2015-01-01

    The introduction and assimilation of chemotherapy to treat pulmonary tuberculosis (TB) during the mid-twentieth century appears at first sight to be a success story dominated by the use of streptomycin in a series of randomised clinical trials run under the auspices of the Medical Research Council (MRC). However, what this standard rhetoric overlooks is the complexity of TB chemotherapy, and the relationship between this and two other ways of treating the disease, bed rest and thoracic surgery. During the late 1940s and 1950s, these three treatment strands overlapped one another, and determining best practice from a plethora of prescribing choices was a difficult task. This article focuses on the clinical decision-making underpinning the evolution of successful treatment for TB using drugs alone. Fears over the risk of streptomycin-resistant organisms entering the community meant that, initially, the clinical application of streptomycin was limited. Combining it with other drugs lessened this risk, but even so the potential of chemotherapy as a curative option for TB was not immediately apparent. The MRC ran a series of clinical trials in the post-war period but not all of their recommendations were adopted by clinicians in the field. Rather, a range of different determinants, including the timing of trials, the time taken for results to emerge, and whether these results ‘fitted’ with individual experience all influenced the translation of trial results into clinical practice. PMID:25766538

  17. BaP-induced DNA damage initiated p53-independent necroptosis via the mitochondrial pathway involving Bax and Bcl-2.

    PubMed

    Jiang, Y; Chen, X; Yang, G; Wang, Q; Wang, J; Xiong, W; Yuan, J

    2013-12-01

    Benzo(a)pyrene (BaP), a typical environmental carcinogen, can induce cell death both by protein 53 or tumor protein 53 (p53)-independent and -dependent pathways. However, little is known about the molecular mechanisms of p53-independent pathways in BaP-induced cell death. In this study, cells with different genetic background (including p53-proficient human fetal lung fibroblast cell lines (MRC-5), p53-deficient human non-small-cell lung carcinoma cell lines (H1299), and p53-knockdown cell lines (MRC-5(p53-/-))) were used to establish models of BaP-induced cell death. The results showed that BaP (8, 16, 32, and 64 μM) induced necroptotic cell death in the cell lines. The necroptotic cell death and DNA damage were concurrently observed. In the three cell lines, at 24 h after treatment, BaP (8-64 μM) upregulated expressions of BAX, BCL-2, and cleaved caspase-3 proteins, but not their messenger RNA levels. The findings suggested that BaP-induced necroptosis was modulated by the p53-independent pathway, which was related to the induction of BAX, decreased expression of BCL-2, and activation of caspase-3.

  18. Application of powder metallurgy techniques to produce improved bearing elements for liquid rocket engines

    NASA Technical Reports Server (NTRS)

    Moracz, D. J.; Shipley, R. J.; Moxson, V. S.; Killman, R. J.; Munson, H. E.

    1992-01-01

    The objective was to apply powder metallurgy techniques for the production of improved bearing elements, specifically balls and races, for advanced cryogenic turbopump bearings. The materials and fabrication techniques evaluated were judged on the basis of their ability to improve fatigue life, wear resistance, and corrosion resistance of Space Shuttle Main Engine (SSME) propellant bearings over the currently used 440C. An extensive list of candidate bearing alloys in five different categories was considered: tool/die steels, through hardened stainless steels, cobalt-base alloys, and gear steels. Testing of alloys for final consideration included hardness, rolling contact fatigue, cross cylinder wear, elevated temperature wear, room and cryogenic fracture toughness, stress corrosion cracking, and five-ball (rolling-sliding element) testing. Results of the program indicated two alloys that showed promise for improved bearing elements. These alloys were MRC-2001 and X-405. 57mm bearings were fabricated from the MRC-2001 alloy for further actual hardware rig testing by NASA-MSFC.

  19. Comparative genomics and mutagenesis analyses of choline metabolism in the marine R oseobacter clade

    PubMed Central

    Lidbury, Ian; Kimberley, George; Scanlan, David J.; Murrell, J. Colin

    2015-01-01

    Summary Choline is ubiquitous in marine eukaryotes and appears to be widely distributed in surface marine waters; however, its metabolism by marine bacteria is poorly understood. Here, using comparative genomics and molecular genetic approaches, we reveal that the capacity for choline catabolism is widespread in marine heterotrophs of the marine Roseobacter clade (MRC). Using the model bacterium R uegeria pomeroyi, we confirm that the bet A, bet B and bet C genes, encoding choline dehydrogenase, betaine aldehyde dehydrogenase and choline sulfatase, respectively, are involved in choline metabolism. The bet T gene, encoding an organic solute transporter, was essential for the rapid uptake of choline but not glycine betaine (GBT). Growth of choline and GBT as a sole carbon source resulted in the re‐mineralization of these nitrogen‐rich compounds into ammonium. Oxidation of the methyl groups from choline requires formyltetrahydrofolate synthetase encoded by fhs in R . pomeroyi, deletion of which resulted in incomplete degradation of GBT. We demonstrate that this was due to an imbalance in the supply of reducing equivalents required for choline catabolism, which can be alleviated by the addition of formate. Together, our results demonstrate that choline metabolism is ubiquitous in the MRC and reveal the role of Fhs in methyl group oxidation in R . pomeroyi. PMID:26058574

  20. Involvement of citizens in hazardous waste management and use of recycling centres in the city of Madrid (Spain).

    PubMed

    Díaz, María José; Martínez, Elvira; Piñeiro, Concepción; Palavecinos, Mireya; Benayas, Javier; Toribio, M Angeles

    2012-07-01

    In Spain, hazardous household waste management by citizens occurs via fixed recycling centres (FRC) and mobile recycling centres (MRC) which usually depend on local governments. This paper addresses a request by the Madrid City Council, in an attempt to improve the service it provides to the city of Madrid. The aim of the study involved analysing the information people possess in relation to hazardous waste and to the use of available equipment, and conducting a post-evaluation of the effectiveness of an environmental communication campaign conducted by the Madrid City Council and aimed at providing awareness of the existence of new FRCs and MRCs. To this end, a questionnaire was conducted with 5644 inhabitants of the city of Madrid. Qualitative data was categorized using content analysis followed by chi-squared tests, considering some socio-demographic characteristics of the sample, such as age or place of residence (district). Communication campaigns influenced citizen awareness of what constituted hazardous waste, of how to properly separate waste and of the existence of FRCs and MRCs. However, few citizens actually used FRCs or MRC (18% across four districts), a fact that might be related to a lack of knowledge of downstream waste treatment issues, or to self-limiting hindrances to householders, such as distance to recycling centres. It is recommended that future communication campaigns investigate householder needs and pre-conceptions in relation to recycling, as well as tailored education aimed at addressing the barriers, perceived or otherwise, facing citizens.

  1. Clathrin-mediated endocytosis of gold nanoparticles in vitro.

    PubMed

    Ng, Cheng Teng; Tang, Florence Mei Ai; Li, Jasmine Jia'en; Ong, Cynthia; Yung, Lanry Lin Yue; Bay, Boon Huat

    2015-02-01

    Gold nanoparticles (AuNPs) have potential biomedical and scientific applications. In this study, we evaluated the uptake and internalization of FBS-coated 20 nm AuNPs into lung fibroblasts and liver cells by different microscopy techniques. AuNP aggregates were observed inside MRC5 lung fibroblasts and Chang liver cells under light microscopy, especially after enhancement with automegallography. Clusters of AuNPs were observed to be adsorbed on the cell surface by scanning electron microscopy. Ultrathin sections showed that AuNPs were mainly enclosed within cytoplasmic vesicles when viewed under transmission electron microscopy. We also investigated the mechanism of uptake for AuNPs, using endocytosis inhibitors and quantification of Au with inductively coupled plasma mass spectrometry. Cells treated with concanavalin A and chlorpromazine showed significant decrease of Au uptake in MRC5 lung fibroblasts and Chang liver cells, respectively, implying that the uptake of AuNPs was facilitated by clathrin-mediated endocytosis. It would therefore appear that uptake of 20 nm AuNPs in both cell types with different tissues of origin, was dependent upon clathrin-mediated endocytosis.

  2. Application of powder metallurgy technique to produce improved bearing elements for cryogenic aerospace engine turbopumps

    NASA Technical Reports Server (NTRS)

    Moxson, V. S.; Moracz, D. J.; Bhat, B. N.; Dolan, F. J.; Thom, R.

    1987-01-01

    Traditionally, vacuum melted 440C stainless steel is used for high performance bearings for aerospace cryogenic systems where corrosion due to condensation is a major concern. For the Space Shuttle Main Engine (SSME), however, 440C performance in the high-pressure turbopumps has been marginal. A basic assumption of this study was that powder metallurgy, rather than cast/wrought, processing would provide the finest, most homogeneous bearing alloy structure. Preliminary testing of P/M alloys (hardness, corrosion resistance, wear resistance, fatigue resistance, and fracture toughness) was used to 'de-select' alloys which did perform as well as baseline 440C. Five out of eleven candidate materials (14-4/6V, X-405, MRC-2001, T-440V, and D-5) based on preliminary screening were selected for the actual rolling-sliding five-ball testing. The results of this test were compared with high-performance vacuum-melted M50 bearing steel. The results of the testing indicated outstanding performance of two P/M alloys, X-405 and MRC-2001, which eventually will be further evaluated by full-scale bearing testing.

  3. Comparative genomics and mutagenesis analyses of choline metabolism in the marine Roseobacter clade.

    PubMed

    Lidbury, Ian; Kimberley, George; Scanlan, David J; Murrell, J Colin; Chen, Yin

    2015-12-01

    Choline is ubiquitous in marine eukaryotes and appears to be widely distributed in surface marine waters; however, its metabolism by marine bacteria is poorly understood. Here, using comparative genomics and molecular genetic approaches, we reveal that the capacity for choline catabolism is widespread in marine heterotrophs of the marine Roseobacter clade (MRC). Using the model bacterium Ruegeria pomeroyi, we confirm that the betA, betB and betC genes, encoding choline dehydrogenase, betaine aldehyde dehydrogenase and choline sulfatase, respectively, are involved in choline metabolism. The betT gene, encoding an organic solute transporter, was essential for the rapid uptake of choline but not glycine betaine (GBT). Growth of choline and GBT as a sole carbon source resulted in the re-mineralization of these nitrogen-rich compounds into ammonium. Oxidation of the methyl groups from choline requires formyltetrahydrofolate synthetase encoded by fhs in R. pomeroyi, deletion of which resulted in incomplete degradation of GBT. We demonstrate that this was due to an imbalance in the supply of reducing equivalents required for choline catabolism, which can be alleviated by the addition of formate. Together, our results demonstrate that choline metabolism is ubiquitous in the MRC and reveal the role of Fhs in methyl group oxidation in R. pomeroyi. PMID:26058574

  4. Gas-diffusion-layer structural properties under compression via X-ray tomography

    NASA Astrophysics Data System (ADS)

    Zenyuk, Iryna V.; Parkinson, Dilworth Y.; Connolly, Liam G.; Weber, Adam Z.

    2016-10-01

    There is a need to understand the structure properties of gas-diffusion layers (GDLs) in order to optimize their performance in various electrochemical devices. This information is important for mathematical modelers, experimentalists, and designers. In this article, a comprehensive study of a large set of commercially available GDLs' porosity, tortuosity, and pore-size distribution (PSD) under varying compression is presented in a single study using X-ray computed tomography (CT), which allows for a noninvasive measurement. Porosities and PSDs are directly obtained from reconstructed stacks of images, whereas tortuosity is computed with a finite-element simulation. Bimodal PSDs due to the presence of binder are observed for most of the GDLs, approaching unimodal distributions at high compressions. Sample to sample variability is conducted to show that morphological properties hold across various locations. Tortuosity values are the lowest for MRC and Freudenberg, highest for TGP, and in-between for SGL papers. The exponents for the MRC and Freudenberg tortuosity demonstrate a very small dependence on compression because the shapes of the pores are spherical indicating minimal heterogeneity. From the representative-elementary-volume studies it is shown that domains of 1 × 1 mm in-plane and full thickness in through-plane directions accurately represent GDL properties.

  5. Osmoregulatory strategies in natural populations of the black-chinned tilapia Sarotherodon melanotheron exposed to extreme salinities in West African estuaries.

    PubMed

    Lorin-Nebel, Catherine; Avarre, Jean-Christophe; Faivre, Nicolas; Wallon, Sophie; Charmantier, Guy; Durand, Jean-Dominique

    2012-08-01

    The effect of salinity was studied in natural populations of the black-chinned tilapia (Sarotherodon melanotheron) from West Africa. This euryhaline species colonizes nearly all coastal environments from bays to lagoons characterized by salinities ranging from fresh water to hypersaline water over 100 ‰. Individuals were sampled during the dry season at several locations characterized by different levels of salinity (3-102 ‰). Their osmotic status and their gills were analyzed. The branchial mitochondria-rich cells (MRC), localized at the basis of the filaments and along the lamellae in fish taken from the saline stations, showed a wide plasticity with significant differences in their number and size. The most striking results were a significant larger area (≈3x) and a higher number (≈55x) of MRC at high salinity (102 ‰) compared to low salinity (3 ‰). The major ion transporters and channels were localized by immunocytochemistry and different expression patterns have been recorded between stations. Despite an increased Na⁺/K⁺-ATPase (NKA) α-subunit expression and NKA activity, pointing to an increased monovalent ion excretion, a severe osmotic imbalance was recorded in animals living in hypersaline environments.

  6. Heterogeneous fluorescence intermittency in single layer reduced graphene oxide

    NASA Astrophysics Data System (ADS)

    Si, Jixin; Volkan-Kacso, Sandor; Eltom, Ahmed; Morozov, Yurii; McDonald, Matthew P.; Ruth, Anthony; Kuno, Masaru; Janko, Boldizsar

    Fluorescence intermittency, or blinking, has been observed in a wide range of systems, including quantum dots, nanorods, and nanowires. Striking similarities have been documented in the optical response of these nanoscale emitters. However, the mechanism behind blinking still remains elusive. For the first time, blinking has been observed in a two-dimensional system in recent experiments on reduced graphene oxide (rGO). Here we reveal the power spectral density (PSD) of the blinking in rGO shares the same 1/f-like behavior of previously known blinking systems; meanwhile, the heterogeneous dynamic evolution and spatial correlation make rGO a unique blinking system. To investigate the origin of blinking, we self-consistently explain the evolution of rGO blinking using the phenomenological multiple recombination center (MRC) model that captures common features of nanoscale blinking. Furthermore, tight binding method and ab-initio method calculations of carbon nanodots are utilized to look for the microscopic structure corresponding to the RCs in the MRC model. M. K. thanks the American Chemical Society Petroleum Research Fund, the Army Research Office (W911NF-12-1-0578) for support. B.J. was supported in part by the U. S. DOE, Office of Science, Office of Basic Energy Sciences, under Contract W-31-109-Eng-38.

  7. PL37: a new hope in the treatment of painful diabetic neuropathy?

    PubMed

    Tesfaye, Solomon

    2016-04-01

    Solomon Tesfaye speaks to Nick Ward, Commissioning Editor: Solomon Tesfaye, MB ChB, MD, FRCP, speaks about PL37; the first orally administered dual inhibitor of enkephalinases and its potential role in the treatment of painful diabetic neuropathy. Solomon Tesfaye is a Consultant Physician/Endocrinologist at Sheffield Teaching Hospitals and Honorary Professor of Diabetic Medicine at the University of Sheffield. His research projects include the epidemiology, risk factors, pathogenesis, CNS involvement and treatment of diabetic neuropathy and neuropathic pain. He was awarded the Prestigious Camillo Golgi Prize of the European Association for the Study of Diabetes (EASD) in 2014 for major scientific contributions in diabetic neuropathy. He has had international leadership roles including chairmanship of the International Expert Group on Diabetic Neuropathy, and of NEURODIAB (2006-2009). He is also a member of the Science and Research Committee of Diabetes UK; a review panel member for the MRC, a Board Member of the Global Quantitative Sensation Testing Society; a member of the Advisory Council of the Neuropathy Trust; and Secretary of International Insulin Foundation. He has served as a member of the MRC, JDRF, NIDDK and UK NIHR scientific review panels and as a member of a Diabetes and Neuropathic Pain Review Group for NICE. PMID:26984197

  8. Fusaproliferin production by Fusarium subglutinans and its toxicity to Artemia salina, SF-9 insect cells, and IARC/LCL 171 human B lymphocytes.

    PubMed Central

    Logrieco, A; Moretti, A; Fornelli, F; Fogliano, V; Ritieni, A; Caiaffa, M F; Randazzo, G; Bottalico, A; Macchia, L

    1996-01-01

    Fusarium subglutinans is an important pathogen of maize and other commodities worldwide. We examined MRC-115 and 71 other F. subglutinans strains from various geographic areas for their ability to synthesize fusaproliferin, a novel toxic sesterterpene recently isolated from F. proliferatum. Fusaproliferin production ranged from 30 to 1,500 micrograms/g of dried ground substrate, with 33 strains producing more than 500 micrograms/g. In particular, strain MRC-115 produced as much as 1,100 to 1,300 micrograms/g. In toxicity studies of two invertebrate models, fusaproliferin was toxic to Artemia salina (50% lethal dose, 53.4 microM) and to the lepidopteran cell line SF-9 (50% cytotoxic concentration, approximately 70 microM, after a 48-h exposure). Fusaproliferin was also toxic to the human nonneoplastic B-lymphocyte cell line IARC/LCL 171 (50% cytotoxic concentration, approximately 55 microM in culture in stationary phase after a 48-h exposure). Experiments performed will cells exposed at seeding suggested a possible cytostatic effect at subtoxic concentrations. PMID:8795229

  9. Leigh Syndrome in Childhood: Neurologic Progression and Functional Outcome

    PubMed Central

    Lee, Jin Sook; Kim, Hunmin; Lim, Byung Chan; Hwang, Hee; Choi, Jieun; Kim, Ki Joong; Hwang, Yong Seung

    2016-01-01

    Background and Purpose Few studies have analyzed the clinical course and functional outcome in Leigh syndrome (LS). The aim of this study was to determine the clinical, radiological, biochemical, and genetic features of patients with LS, and identify prognostic indicators of the disease progression and neurological outcome. Methods Thirty-nine patients who had been diagnosed with LS at the Seoul National University Children's Hospital were included. Their medical records, neuroimaging findings, and histological/biochemical findings of skeletal muscle specimens were reviewed. Targeted sequencing of mitochondrial DNA was performed based on mitochondrial respiratory chain (MRC) enzyme defects. Results Isolated complex I deficiency was the most frequently observed MRC defect (in 42% of 38 investigated patients). Mitochondrial DNA mutations were identified in 11 patients, of which 81.8% were MT-ND genes. The clinical outcome varied widely, from independent daily activity to severe disability. Poor functional outcomes and neurological deterioration were significantly associated with early onset (before an age of 1 year) and the presence of other lesions additional to basal ganglia involvement in the initial neuroimaging. Conclusions The neurological severity and outcome of LS may vary widely and be better than those predicted based on previous studies. We suggest that age at onset and initial neuroimaging findings are prognostic indicators in LS. PMID:27074294

  10. Potential gastroprotective effect of novel cyperenoic acid/quinone derivatives in human cell cultures.

    PubMed

    Theoduloz, Cristina; Carrión, Ivanna Bravo; Pertino, Mariano Walter; Valenzuela, Daniela; Schmeda-Hirschmann, Guillermo

    2012-11-01

    The stem bark of Tabebuia species and the rhizomes of Jatropha isabelii are used in Paraguayan traditional medicine to treat gastric lesions and as anti-inflammatory agents. The sesquiterpene cyperenoic acid obtained from J. isabelii has been shown to display a gastroprotective effect in animal models of induced gastric ulcers while the quinone lapachol shows several biological effects associated with the use of the crude drug. The aim of this work was to prepare hybrid molecules presenting a terpene and a quinone moiety and to obtain an assessment of the gastroprotective activity of the new compounds using human cell cultures (MRC-5 fibroblasts and AGS epithelial gastric cells). Eight compounds, including the natural products and semisynthetic derivatives were assessed for proliferation of MRC-5 fibroblasts, protection against sodium taurocholate-induced damage, prostaglandin E2 content, and stimulation of cellular-reduced glutathione synthesis in AGS cells. The following antioxidant assays were performed: DPPH discoloration, scavenging of the superoxide anion, and inhibition of induced lipoperoxidation in erythrocyte membranes. 3-Hydroxy-β-lapachone (3) and cyperenoic acid (4) stimulated fibroblast proliferation. Lapachol (1), dihydroprenyl lapachol (2), 3-hydroxy-β-lapachone (3), and lapachoyl cyperenate (6) protected against sodium taurocholate-induced damage in AGS cells. Lapachol (1) and dihydroprenyl lapachoyl cyperenate (7) significantly stimulated prostaglandin E2 synthesis in AGS cells. Compounds 3, 4, and 7 raised reduced glutathione levels in AGS cells. The hybrid compounds presented activities different than those of the starting sesquiterpene or quinones.

  11. Unravelling the 'tangled web': chemotherapy for tuberculosis in Britain, 1940-70 the William Bynum prize essay.

    PubMed

    Leeming-Latham, Clare

    2015-04-01

    The introduction and assimilation of chemotherapy to treat pulmonary tuberculosis (TB) during the mid-twentieth century appears at first sight to be a success story dominated by the use of streptomycin in a series of randomised clinical trials run under the auspices of the Medical Research Council (MRC). However, what this standard rhetoric overlooks is the complexity of TB chemotherapy, and the relationship between this and two other ways of treating the disease, bed rest and thoracic surgery. During the late 1940s and 1950s, these three treatment strands overlapped one another, and determining best practice from a plethora of prescribing choices was a difficult task. This article focuses on the clinical decision-making underpinning the evolution of successful treatment for TB using drugs alone. Fears over the risk of streptomycin-resistant organisms entering the community meant that, initially, the clinical application of streptomycin was limited. Combining it with other drugs lessened this risk, but even so the potential of chemotherapy as a curative option for TB was not immediately apparent. The MRC ran a series of clinical trials in the post-war period but not all of their recommendations were adopted by clinicians in the field. Rather, a range of different determinants, including the timing of trials, the time taken for results to emerge, and whether these results 'fitted' with individual experience all influenced the translation of trial results into clinical practice.

  12. Novel Zinc(II) Complexes [Zn(atc-Et)₂] and [Zn(atc-Ph)₂]: In Vitro and in Vivo Antiproliferative Studies.

    PubMed

    Lopes, Erica de O; Oliveira, Carolina G de; Silva, Patricia B da; Eismann, Carlos E; Suárez, Carlos A; Menegário, Amauri A; Leite, Clarice Q F; Deflon, Victor M; Pavan, Fernando R

    2016-01-01

    Cisplatin and its derivatives are the main metallodrugs used in cancer therapy. However, low selectivity, toxicity and drug resistance are associated with their use. The zinc(II) (Zn(II)) thiosemicarbazone complexes [Zn(atc-Et)₂] (1) and [Zn(atc-Ph)₂] (2) (atc-R: monovalent anion of 2-acetylpyridine N4-R-thiosemicarbazone) were synthesized and fully characterized in the solid state and in solution via elemental analysis, Fourier transform infrared (FTIR), ultraviolet-visible (UV-Vis) and proton nuclear magnetic resonance (¹H NMR) spectroscopy, conductometry and single-crystal X-ray diffraction. The cytotoxicity of these complexes was evaluated in the HepG2, HeLa, MDA-MB-231, K-562, DU 145 and MRC-5 cancer cell lines. The strongest antiproliferative results were observed in MDA-MB-231 and HepG2 cells, in which these complexes displayed significant selective toxicity (3.1 and 3.6, respectively) compared with their effects on normal MRC-5 cells. In vivo studies were performed using an alternative model (Artemia salina L.) to assure the safety of these complexes, and the results were confirmed using a conventional model (BALB/c mice). Finally, tests of oral bioavailability showed maximum plasma concentrations of 3029.50 µg/L and 1191.95 µg/L for complexes 1 and 2, respectively. According to all obtained results, both compounds could be considered as prospective antiproliferative agents that warrant further research. PMID:27213368

  13. Bias-free procedure for the measurement of the minimum resolvable temperature difference and minimum resolvable contrast

    NASA Astrophysics Data System (ADS)

    Bijl, Piet; Valeton, J. Mathieu

    1999-10-01

    The characterization of electro-optical system performance by means of the standard minimum resolvable temperature difference (MRTD) or the minimum resolvable contrast (MRC) has a number of serious disadvantages. One of the problems is that they depend on the subjective decision criterion of the observer. We present an improved measurement procedure in which the results are free from observer bias. In an adaptive two-alternative forced-choice procedure, both the standard four-bar pattern and a five-bar reference pattern of the same size and contrast are presented consecutively in random order. The observer decides which of the two presentations contains the four-bar pattern. Misjudgments are made if the bars cannot be resolved or are distorted by sampling. The procedure converges to the contrast at which 75% of the observer responses are correct. The reliability of the responses is tested statistically. Curves cut off near the Nyquist frequency, so that it is not necessary to artificially set a frequency limit for sampling array cameras. The procedure enables better and easier measurement, yields more stable results than the standard procedure, and avoids disputes between different measuring teams. The presented procedure is a `quick fix' solution for some of the problems with the MRTD and MRC, and is recommended as long as bar patterns are used as the stimulus. A new and fundamentally better method to characterize electro-optical system performance, called the triangle orientation discrimination threshold was recently proposed by Bijl and Valeton (1998).

  14. Evolution of Clinical Research: A History Before and Beyond James Lind

    PubMed Central

    Bhatt, Arun

    2010-01-01

    The evolution of clinical research traverses a long and fascinating journey. From the first recorded trial of legumes in biblical times to the first randomized controlled of trial of streptomycin in 1946, the history of clinical trial covers a wide variety of challenges - scientific, ethical and regulatory. The famous 1747 scurvy trial conducted by James Lind contained most elements of a controlled trial. The UK Medical Research Council's (MRC) trial of patulin for common cold in 1943 was the first double blind controlled trial. This paved the way for the first randomized control trial of streptomycin in pulmonary tuberculosis carried out in 1946 by MRC of the UK. This landmark trial was a model of meticulousness in design and implementation, with systematic enrolment criteria and data collection compared with the ad hoc nature of other contemporary research. Over the years, as the discipline of controlled trials grew in sophistication and influence, the streptomycin trial continues to be referred to as ground breaking. The ethical advances in human protection include several milestones - Nuremberg Code, Declaration of Helsinki, Belmont Report, and 1996, International Conference on Harmonization Good Clinical Practice guidance. In parallel to ethical guidelines, clinical trials started to become embodied in regulation as government authorities began recognizing a need for controlling medical therapies in the early 20th century. As the scientific advances continue to occur, there will be new ethical and regulatory challenges requiring dynamic updates in ethical and legal framework of clinical trials. PMID:21829774

  15. Sirtuin 1 (SIRT1) Deacetylase Activity and NAD⁺/NADH Ratio Are Imperative for Capsaicin-Mediated Programmed Cell Death.

    PubMed

    Lee, Yi-Hui; Chen, Huei-Yu; Su, Lilly J; Chueh, Pin Ju

    2015-08-26

    Capsaicin is considered a chemopreventive agent by virtue of its selective antigrowth activity, commonly associated with apoptosis, against cancer cells. However, noncancerous cells possess relatively higher tolerance to capsaicin, although the underlying mechanism for this difference remains unclear. Hence, this study aimed to elucidate the differential effects of capsaicin on cell lines from lung tissues by addressing the signal pathway leading to two types of cell death. In MRC-5 human fetal lung cells, capsaicin augmented silent mating type information regulation 1 (SIRT1) deacetylase activity and the intracellular NAD(+)/NADH ratio, decreasing acetylation of p53 and inducing autophagy. In contrast, capsaicin decreased the intracellular NAD(+)/NADH ratio, possibly through inhibition of tumor-associated NADH oxidase (tNOX), and diminished SIRT1 expression leading to enhanced p53 acetylation and apoptosis. Moreover, SIRT1 depletion by RNA interference attenuated capsaicin-induced apoptosis in A549 cancer cells and autophagy in MRC-5 cells, suggesting a vital role for SIRT1 in capsaicin-mediated cell death. Collectively, these data not only explain the differential cytotoxicity of capsaicin but shed light on the distinct cellular responses to capsaicin in cancerous and noncancerous cell lines.

  16. Novel Zinc(II) Complexes [Zn(atc-Et)2] and [Zn(atc-Ph)2]: In Vitro and in Vivo Antiproliferative Studies

    PubMed Central

    Lopes, Erica de O.; de Oliveira, Carolina G.; da Silva, Patricia B.; Eismann, Carlos E.; Suárez, Carlos A.; Menegário, Amauri A.; Leite, Clarice Q. F.; Deflon, Victor M.; Pavan, Fernando R.

    2016-01-01

    Cisplatin and its derivatives are the main metallodrugs used in cancer therapy. However, low selectivity, toxicity and drug resistance are associated with their use. The zinc(II) (ZnII) thiosemicarbazone complexes [Zn(atc-Et)2] (1) and [Zn(atc-Ph)2] (2) (atc-R: monovalent anion of 2-acetylpyridine N4-R-thiosemicarbazone) were synthesized and fully characterized in the solid state and in solution via elemental analysis, Fourier transform infrared (FTIR), ultraviolet-visible (UV-Vis) and proton nuclear magnetic resonance (1H NMR) spectroscopy, conductometry and single-crystal X-ray diffraction. The cytotoxicity of these complexes was evaluated in the HepG2, HeLa, MDA-MB-231, K-562, DU 145 and MRC-5 cancer cell lines. The strongest antiproliferative results were observed in MDA-MB-231 and HepG2 cells, in which these complexes displayed significant selective toxicity (3.1 and 3.6, respectively) compared with their effects on normal MRC-5 cells. In vivo studies were performed using an alternative model (Artemia salina L.) to assure the safety of these complexes, and the results were confirmed using a conventional model (BALB/c mice). Finally, tests of oral bioavailability showed maximum plasma concentrations of 3029.50 µg/L and 1191.95 µg/L for complexes 1 and 2, respectively. According to all obtained results, both compounds could be considered as prospective antiproliferative agents that warrant further research. PMID:27213368

  17. A study testing the usefulness of a dish-based food-frequency questionnaire developed for epidemiological studies in Korea.

    PubMed

    Kim, Young Ok; Kim, Mi Kyung; Lee, Sang-Ah; Yoon, Young Mi; Sasaki, Satoshi

    2009-04-01

    The purpose of the present study was to test the usefulness of dish items selected in developing a dish-based FFQ (DFFQ) to be used for epidemiological studies in Korea. The dietary data of 6817 subjects from the 2001 Korean National Health and Nutrition Examination Survey were used for the analysis. The 24 h recall method was employed for the dietary survey. Initially, ninety-five dish items were selected in developing the DFFQ based on consumption frequency, contribution of selected nutrients and coverage of between-person variations. The usefulness of the selected ninety-five dish items was tested based on their degree of contribution in supplying nutrients in the cumulative percentage contribution (cPC), as well as on their degree of explanation for between-person variation in the cumulative regression coefficient (cMRC). According to the results, the ninety-five selected dish items accounted for an average of 92.3 % of seventeen nutrients consumed by the study subjects based on cPC estimation. The top twenty items among the ninety-five dish items covered 70 to 91 % of the between-person variation for the seventeen nutrients based on cMRC estimation. Thus, the results suggest that the ninety-five items would be useful in developing a FFQ for use in epidemiological studies of Koreans, within less than 10 % underestimation. PMID:18786277

  18. Potential gastroprotective effect of novel cyperenoic acid/quinone derivatives in human cell cultures.

    PubMed

    Theoduloz, Cristina; Carrión, Ivanna Bravo; Pertino, Mariano Walter; Valenzuela, Daniela; Schmeda-Hirschmann, Guillermo

    2012-11-01

    The stem bark of Tabebuia species and the rhizomes of Jatropha isabelii are used in Paraguayan traditional medicine to treat gastric lesions and as anti-inflammatory agents. The sesquiterpene cyperenoic acid obtained from J. isabelii has been shown to display a gastroprotective effect in animal models of induced gastric ulcers while the quinone lapachol shows several biological effects associated with the use of the crude drug. The aim of this work was to prepare hybrid molecules presenting a terpene and a quinone moiety and to obtain an assessment of the gastroprotective activity of the new compounds using human cell cultures (MRC-5 fibroblasts and AGS epithelial gastric cells). Eight compounds, including the natural products and semisynthetic derivatives were assessed for proliferation of MRC-5 fibroblasts, protection against sodium taurocholate-induced damage, prostaglandin E2 content, and stimulation of cellular-reduced glutathione synthesis in AGS cells. The following antioxidant assays were performed: DPPH discoloration, scavenging of the superoxide anion, and inhibition of induced lipoperoxidation in erythrocyte membranes. 3-Hydroxy-β-lapachone (3) and cyperenoic acid (4) stimulated fibroblast proliferation. Lapachol (1), dihydroprenyl lapachol (2), 3-hydroxy-β-lapachone (3), and lapachoyl cyperenate (6) protected against sodium taurocholate-induced damage in AGS cells. Lapachol (1) and dihydroprenyl lapachoyl cyperenate (7) significantly stimulated prostaglandin E2 synthesis in AGS cells. Compounds 3, 4, and 7 raised reduced glutathione levels in AGS cells. The hybrid compounds presented activities different than those of the starting sesquiterpene or quinones. PMID:23047252

  19. Gaseous nitrogen oxides stimulate cell cycle progression by retinoblastoma phosphorylation via activation of cyclins/Cdks [correction].

    PubMed

    Chen, Jing-Hsien; Tseng, Tsui-Hwa; Ho, Yung-Chyan; Lin, Hui-Hsuan; Lin, Wea-Lung; Wang, Chau-Jong

    2003-11-01

    Nitrogen oxides (NOx) are important indoor and outdoor air pollutants. Many studies have indicated that NOx gas causes lung tissue damage by its oxidation properties and its free radicals. In a previous study we demonstrated that NOx gas induced proliferation of human lung fibroblast MRC-5 cells. In this study we show that NOx gas stimulates MRC-5 cell proliferation by retinoblastoma (Rb) phosphorylation via activation of cyclin-cell division protein kinase (cdk) complexes [correction]. Western blot and immunoprecipitation data showed that NOx gas increased the expressions of cyclinA/cdk2, cyclinD1/cdk4, and cyclinE/cdk2 complexes in the cells at 9 h after treatment. The levels of phospho-Rb were also increased and cdk inhibitors (CKIs) p27 and p16 were apparently decreased. These data suggested that NOx gas stimulates cell-cycle progression by Rb phosphorylation via activation of cyclin-cdk complexes and inhibition of CKIs. In conclusion, the NOx-gas that induced lung fibroblast cell proliferation by stimulation of cell-cycle progression may contribute to lung fibrosis by NOx pollutants.

  20. Dyspnea-12 Is a Valid and Reliable Measure of Breathlessness in Patients With Interstitial Lung Disease

    PubMed Central

    Swigris, Jeffrey; Russell, Anne-Marie; Moosavi, Shakeeb H.; Ng Man Kwong, Georges; Longshaw, Mark; Jones, Paul W.

    2011-01-01

    Objective: In this study, we aimed to determine the validity and reliability of the Dyspnea-12 questionnaire (D-12) for the assessment of breathlessness in patients with interstitial lung disease (ILD). Methods: A total of 101 patients with ILD completed the D-12 (scale range, 0-36, with a high score indicating worse dyspnea), Medical Research Council (MRC) dyspnea scale, St. George Respiratory Questionnaire (SGRQ), and Hospital Anxiety and Depression Scale (HADS) at baseline, and 84 patients completed the D-12 and a global health transition score at follow-up 2 weeks later. D-12 psychometric properties, including floor and ceiling effects, internal consistency, test-retest reliability, and construct validity were examined. Results: The D-12 showed good internal consistency (Cronbach α, 0.93) and repeatability (intraclass correlation coefficient, 0.94). Its scores were significantly associated with MRC grade (r = 0.59; P < .001), SGRQ (symptoms, r = 0.57; activities, r = 0.78; impacts, r = 0.75; total, r = 0.79; P < .001). Factor analysis confirmed the previously determined structure of the D-12 in this patient group. Conclusion: In patients with ILD, the D-12, a patient-reported measure of dyspnea severity that requires no reference to activity, is a reliable and valid instrument. It is short, simple to complete, and easy to score. PMID:20595454

  1. Chemical Characterization and Cytotoxic Activity of Blueberry Extracts (cv. Misty) Cultivated in Brazil.

    PubMed

    Massarotto, Giovana; Barcellos, Thiago; Garcia, Charlene Silvestrin Celi; Brandalize, Ana Paula Carneiro; Moura, Sidnei; Schwambach, Joséli; Henriques, João Antonio Pêgas; Roesch-Ely, Mariana

    2016-08-01

    Vaccinium corymbosum (L.) varieties cultivation is relatively recent in Brazil, but its production has been intensified given its good adaptability to the Southern Brazil climate. Blueberries are a rich source of phenolic compounds and contain significant levels of anthocyanins, flavonols, chlorogenic acids, and procyanidins, which lead to different biological activities. Chemical identification of skin and whole hydroalcoholic blueberry extracts (ExtSB and ExtWB) revealed the presence of anthocyanins concentrated in the skin and others chemicals compounds as quercetin glycosides, proanthocyanins dimers, citric, and chlorogenic acid in the pulp. Selectivity for tumor cell lines (Hep-2, HeLa, HT-29) using ExtSB and ExtWB extracts was observed through MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay after 24 h of treatment when compared to nontumor cells (MRC-5). Morphological changes and late stages of apoptotic and necrosis process were seen in HT-29 cell line after ExtWB treatment, compared to nontumor cell line MRC-5. These results are in agreement with other studies that indicate the activity of compounds such as anthocyanins and other molecules found in Southern Highbush blueberry variety, attributed to promote beneficial effects on health that may respond as cytotoxic natural agent and contribute to cancer treatment.

  2. Serum VEGF levels are related to the presence of pulmonary arterial hypertension in systemic sclerosis

    PubMed Central

    Papaioannou, Andriana I; Zakynthinos, Epaminondas; Kostikas, Konstantinos; Kiropoulos, Theodoros; Koutsokera, Angela; Ziogas, Athanasios; Koutroumpas, Athanasios; Sakkas, Lazaros; Gourgoulianis, Konstantinos I; Daniil, Zoe D

    2009-01-01

    Background The association between systemic sclerosis and pulmonary arterial hypertension (PAH) is well recognized. Vascular endothelial growth factor (VEGF) has been reported to play an important role in pulmonary hypertension. The aim of the present study was to examine the relationship between systolic pulmonary artery pressure, clinical and functional manifestations of the disease and serum VEGF levels in systemic sclerosis. Methods Serum VEGF levels were measured in 40 patients with systemic sclerosis and 13 control subjects. All patients underwent clinical examination, pulmonary function tests and echocardiography. Results Serum VEGF levels were higher in systemic sclerosis patients with sPAP ≥ 35 mmHg than in those with sPAP < 35 mmHg (352 (266, 462 pg/ml)) vs (240 (201, 275 pg/ml)) (p < 0.01), while they did not differ between systemic sclerosis patients with sPAP < 35 mmHg and controls. Serum VEGF levels correlated to systolic pulmonary artery pressure, to diffusing capacity for carbon monoxide and to MRC dyspnea score. In multiple linear regression analysis, serum VEGF levels, MRC dyspnea score, and DLCO were independent predictors of systolic pulmonary artery pressure. Conclusion Serum VEGF levels are increased in systemic sclerosis patients with sPAP ≥ 35 mmHg. The correlation between VEGF levels and systolic pulmonary artery pressure may suggest a possible role of VEGF in the pathogenesis of PAH in systemic sclerosis. PMID:19426547

  3. Automated linkage analysis in psychiatric disorders

    SciTech Connect

    He, L.; Mansfield, D.C.; Brown, A.F.; Green, D.K.

    1995-06-19

    A genome-wide search for linkage of microsatellite markers to chromosomal loci containing genes responsible for the major psychoses is a laborious task which can be carried out with greater speed and economy by introducing automation to several steps in the procedure. We describe the use of the Automated Linkage Preprocessor (ALP) program for the computer analysis of the waveform generated by fluorescein-labelled markers after electrophoretic separation. (To obtain a copy send a request to A.F. Brown at the below MRC address or use Anonymous FTP to ftp.hgu.mrc.ac.uk. Software is in directory pub/ALP.) The program runs on a PC in the Microsoft Windows environment, and is used in conjunction with an automated laser fluorescence (ALF) sequencer (Pharmacia) and its Fragment Manager{trademark} software to detect and size the PCR products, filter out peaks of fluorescence due to nonallele fragments, and generate genotypes in a format suitable for direct input to standard linkage analysis programs. The method should offer the advantages of speed, accuracy, and reduced cost. Its use in linkage studies in a large family with manic-depressive illness is discussed. 14 refs., 3 figs., 1 tab.

  4. The UPBEAT depression and coronary heart disease programme: using the UK medical research council framework to design a nurse-led complex intervention for use in primary care

    PubMed Central

    2012-01-01

    Background Depression is common in coronary heart disease (CHD) and increases the incidence of coronary symptoms and death in CHD patients. Interventions feasible for use in primary care are needed to improve both mood and cardiac outcomes. The UPBEAT-UK programme of research has been funded by the NHS National Institute for Health Research (NIHR) to explore the relationship between CHD and depression and to develop a new intervention for use in primary care. Methods Using the Medical Research Council (MRC) guidelines for developing and evaluating complex interventions, we conducted a systematic review and qualitative research to develop a primary care-based nurse-led intervention to improve mood and cardiac outcomes in patients with CHD and depression. Iterative literature review was used to synthesise our empirical work and to identify evidence and theory to inform the intervention. Results We developed a primary care-based nurse-led personalised care intervention which utilises elements of case management to promote self management. Following biopsychosocial assessment, a personalised care plan is devised. Nurses trained in behaviour change techniques facilitate patients to address the problems important to them. Identification and utilisation of existing resources is promoted. Nurse time is conserved through telephone follow up. Conclusions Application of the MRC framework for complex interventions has allowed us to develop an evidence based intervention informed by patient and clinician preferences and established theory. The feasibility and acceptability of this intervention is now being tested further in an exploratory trial. PMID:23234253

  5. Evaluation of sustained release polylactate electron donors for removal of hexavalent chromium from contaminated groundwater

    SciTech Connect

    Brodie, E.L.; Joyner, D. C.; Faybishenko, B.; Conrad, M. E.; Rios-Velazquez, C.; Mork, B.; Willet, A.; Koenigsberg, S.; Herman, D.; Firestone, M. K.; Hazen, T. C.; Malave, Josue; Martinez, Ramon

    2011-02-15

    To evaluate the efficacy of bioimmobilization of Cr(VI) in groundwater at the Department of Energy Hanford site, we conducted a series of microcosm experiments using a range of commercial electron donors with varying degrees of lactate polymerization (polylactate). These experiments were conducted using Hanford Formation sediments (coarse sand and gravel) immersed in Hanford groundwater, which were amended with Cr(VI) and several types of lactate-based electron donors (Hydrogen Release Compound, HRC; primer-HRC, pHRC; extended release HRC) and the polylactate-cysteine form (Metal Remediation Compound, MRC). The results showed that polylactate compounds stimulated an increase in bacterial biomass and activity to a greater extent than sodium lactate when applied at equivalent carbon concentrations. At the same time, concentrations of headspace hydrogen and methane increased and correlated with changes in the microbial community structure. Enrichment of Pseudomonas spp. occurred with all lactate additions, and enrichment of sulfate-reducing Desulfosporosinus spp. occurred with almost complete sulfate reduction. The results of these experiments demonstrate that amendment with the pHRC and MRC forms result in effective removal of Cr(VI) from solution most likely by both direct (enzymatic) and indirect (microbially generated reductant) mechanisms.

  6. As Depressing As It Was Predictable?

    PubMed Central

    Timmermann, Carsten

    2007-01-01

    Summary In recent years lung cancer specialists have complained that due to stigma resulting from the association of the disease with smoking, theirs is a neglected field. This paper demonstrates that in the 1950s and 1960s, when the British Medical Research Council (MRC) started to organize clinical trials for various forms of cancer, this was not the case. Rather, the organizers of these trials saw lung cancer as a particularly promising object of research, for much was known about the disease. The cancer trials were part of a strategy to use the Randomized Controlled Trial (RCT) technology to cement the role of the MRC as the dominant body overseeing medical research in Britain. The organization of the trials, however, turned out to be very difficult, due to ethical problems and the dominance of one form of therapy, surgery. The trial results were deeply disappointing. I argue that these frustrating results contributed to the notion of hopelessness that has come to surround lung cancer, and to the shift of focus from cure to prevention that was triggered by epidemiologic studies identifying tobacco smoke as the main cause of the disease. The paper deals with an important episode in the history of clinical cancer research in postwar Britain, illustrating the ethical and practical problems faced by the organizers. PMID:17369673

  7. [Effects of organic-inorganic mixed fertilizers on rice yield and nitrogen use efficiency].

    PubMed

    Zhang, Xiao-li; Meng, Lin; Wang, Qiu-jun; Luo, Jia; Huang, Qi-wei; Xu, Yang-chun; Yang, Xing-ming; Shen, Qi-rong

    2009-03-01

    A field experiment was carried to study the effects of organic-inorganic mixed fertilizers on rice yield, nitrogen (N) use efficiency, soil N supply, and soil microbial diversity. Rapeseed cake compost (RCC), pig manure compost (PMC), and Chinese medicine residue compost (MRC) were mixed with chemical N, P and K fertilizers. All the treatments except CK received the same rate of N. The results showed that all N fertilizer application treatments had higher rice yield (7918.8-9449.2 kg x hm(-2)) than the control (6947.9 kg x hm(-2)). Compared with that of chemical fertilizers (CF) treatment (7918.8 kg x hm(-2)), the yield of the three organic-inorganic mixed fertilizers treatments ranged in 8532.0-9449.2 kg x hm(-2), and the increment was 7.7%-19.3%. Compared with treatment CF, the treatments of organic-inorganic mixed fertilizers were significantly higher in N accumulation, N transportation efficiency, N recovery rate, agronomic N use efficiency, and physiological N use efficiency. These mixed fertilizers treatments promoted rice N uptake and improved soil N supply, and thus, increased N use efficiency, compared with treatments CF and CK. Neighbor joining analysis indicated that soil bacterial communities in the five treatments could be classified into three categories, i.e., CF and CK, PMC and MRC, and RCC, implying that the application of exogenous organic materials could affect soil bacterial communities, while applying chemical fertilizers had little effect on them.

  8. Power Scaling of Uplink Massive MIMO Systems With Arbitrary-Rank Channel Means

    NASA Astrophysics Data System (ADS)

    Zhang, Qi; Jin, Shi; Wong, Kai-Kit; Zhu, Hongbo; Matthaiou, Michail

    2014-10-01

    This paper investigates the uplink achievable rates of massive multiple-input multiple-output (MIMO) antenna systems in Ricean fading channels, using maximal-ratio combining (MRC) and zero-forcing (ZF) receivers, assuming perfect and imperfect channel state information (CSI). In contrast to previous relevant works, the fast fading MIMO channel matrix is assumed to have an arbitrary-rank deterministic component as well as a Rayleigh-distributed random component. We derive tractable expressions for the achievable uplink rate in the large-antenna limit, along with approximating results that hold for any finite number of antennas. Based on these analytical results, we obtain the scaling law that the users' transmit power should satisfy, while maintaining a desirable quality of service. In particular, it is found that regardless of the Ricean $K$-factor, in the case of perfect CSI, the approximations converge to the same constant value as the exact results, as the number of base station antennas, $M$, grows large, while the transmit power of each user can be scaled down proportionally to $1/M$. If CSI is estimated with uncertainty, the same result holds true but only when the Ricean $K$-factor is non-zero. Otherwise, if the channel experiences Rayleigh fading, we can only cut the transmit power of each user proportionally to $1/\\sqrt M$. In addition, we show that with an increasing Ricean $K$-factor, the uplink rates will converge to fixed values for both MRC and ZF receivers.

  9. Essential oil content of the rhizome of Curcuma purpurascens Bl. (Temu Tis) and its antiproliferative effect on selected human carcinoma cell lines.

    PubMed

    Hong, Sok-Lai; Lee, Guan-Serm; Syed Abdul Rahman, Syarifah Nur; Ahmed Hamdi, Omer Abdalla; Awang, Khalijah; Aznam Nugroho, Nurfina; Abd Malek, Sri Nurestri

    2014-01-01

    Curcuma purpurascens Bl., belonging to the Zingiberaceae family, is known as temu tis in Yogyakarta, Indonesia. In this study, the hydrodistilled dried ground rhizome oil was investigated for its chemical content and antiproliferative activity against selected human carcinoma cell lines (MCF7, Ca Ski, A549, HT29, and HCT116) and a normal human lung fibroblast cell line (MRC5). Results from GC-MS and GC-FID analysis of the rhizome oil of temu tis showed turmerone as the major component, followed by germacrone, ar-turmerone, germacrene-B, and curlone. The rhizome oil of temu tis exhibited strong cytotoxicity against HT29 cells (IC50 value of 4.9 ± 0.4 μg/mL), weak cytotoxicity against A549, Ca Ski, and HCT116 cells (with IC50 values of 46.3 ± 0.7, 32.5 ± 1.1, and 35.0 ± 0.3 μg/mL, resp.), and no inhibitory effect against MCF7 cells. It exhibited mild cytotoxicity against a noncancerous human lung fibroblast cell line (MRC5), with an IC50 value of 25.2 ± 2.7 μg/mL. This is the first report on the chemical composition of this rhizome's oil and its selective antiproliferative effect on HT29. The obtained data provided a basis for further investigation of the mode of cell death.

  10. Microbial community response to addition of polylactate compounds to stimulate hexavalent chromium reduction in groundwater.

    PubMed

    Brodie, Eoin L; Joyner, Dominique C; Faybishenko, Boris; Conrad, Mark E; Rios-Velazquez, Carlos; Malave, Josue; Martinez, Ramon; Mork, Benjamin; Willett, Anna; Koenigsberg, Steven; Herman, Donald J; Firestone, Mary K; Hazen, Terry C

    2011-10-01

    To evaluate the efficacy of bioimmobilization of Cr(VI) in groundwater at the Department of Energy Hanford site, we conducted a series of microcosm experiments using a range of commercial electron donors with varying degrees of lactate polymerization (polylactate). These experiments were conducted using Hanford Formation sediments (coarse sand and gravel) immersed in Hanford groundwater, which were amended with Cr(VI) and several types of lactate-based electron donors (Hydrogen Release Compound, HRC; primer-HRC, pHRC; extended release HRC) and the polylactate-cysteine form (Metal Remediation Compound, MRC). The results showed that polylactate compounds stimulated an increase in bacterial biomass and activity to a greater extent than sodium lactate when applied at equivalent carbon concentrations. At the same time, concentrations of headspace hydrogen and methane increased and correlated with changes in the microbial community structure. Enrichment of Pseudomonas spp. occurred with all lactate additions, and enrichment of sulfate-reducing Desulfosporosinus spp. occurred with almost complete sulfate reduction. The results of these experiments demonstrate that amendment with the pHRC and MRC forms result in effective removal of Cr(VI) from solution most likely by both direct (enzymatic) and indirect (microbially generated reductant) mechanisms.

  11. Final Report - ILAW PCT, VHT, Viscosity, and Electrical Conductivity Model Development, VSL-07R1230-1

    SciTech Connect

    Kruger, Albert A.; Cooley, S. K.; Joseph, I.; Pegg, I. L.; Piepel, G. F.; Gan, H.; Muller, I.

    2013-12-17

    This report describes the results of work and testing specified by the Test Specifications (24590-LAW-TSP-RT-01-013 Rev.1 and 24590-WTP-TSP-RT-02-001 Rev.0), Test Plans (VSL-02T4800-1 Rev.1 & TP-RPP-WTP-179 Rev.1), and Text Exception (24590-WTP-TEF-RT-03-040). The work and any associated testing followed established quality assurance requirements and conducted as authorized. The descriptions provided in this test report are an accurate account of both the conduct of the work and the data collected. Results required by the Test Plans are reported. Also reported are any unusual or anomalous occurrences that are different from the starting hypotheses. The test results and this report have been reviewed and verified.

  12. Final Report - Sulfate Solubility in RPP-WTP HLW Glasses, VSL-06R6780-1, Rev. 0

    SciTech Connect

    Kruger, Albert A.; Pegg, I. L.; Feng, A.; Gan, H.; Kot, W. K.

    2013-12-03

    This report describes the results of work and testing specified by Test Specifications 24590-HLW-TSP-RT-01-006 Rev 1, Test Plans VSL-02T7800-1 Rev 1 and Test Exceptions 24590-HLW-TEF-RT-05-00007. The work and any associated testing followed established quality assurance requirements and were conducted as authorized. The descriptions provided in this report are an accurate account of both the conduct of the work and the data collected. Results required by the Test Plans are reported. Also reported are any unusual or anomalous occurrences that are different from the starting hypotheses. The test results and this report have been reviewed and verified.

  13. Mitochondrial respiratory chain dysfunction modulates metalloproteases -1, -3 and -13 in human normal chondrocytes in culture

    PubMed Central

    2013-01-01

    Background Mitochondrion has an important role in the osteoarthritis (OA) pathology. We have previously demonstrated that the alteration of the mitochondrial respiratory chain (MRC) contributes to the inflammatory response of the chondrocyte. However its implication in the process of cartilage destruction is not well understood yet. In this study we have investigated the relationship between the MRC dysfunction and the regulation of metalloproteases (MMPs) in human normal chondrocytes in culture. Methods Human normal chondrocytes were isolated from human knees obtained form autopsies of donors without previous history of rheumatic disease. Rotenone, 3-Nitropropionic acid (NPA), Antimycin A (AA), Sodium azide and Oligomycin were used to inhibit the activity of the mitochondrial complexes I, II, III, IV and V respectively. The mRNA expression of MMPs -1, -3 and -13 was studied by real time PCR. The intracellular presence of MMP proteins was evaluated by western blot. The liberation of these proteins to the extracellular media was evaluated by ELISA. The presence of proteoglycans in tissue was performed with tolouidin blue and safranin/fast green. Immunohistochemistry was used for evaluating MMPs on tissue. Results Firstly, cells were treated with the inhibitors of the MRC for 24 hours and mRNA expression was evaluated. An up regulation of MMP-1 and -3 mRNA levels was observed after the treatment with Oligomycin 5 and 100 μg/ml (inhibitor of the complex V) for 24 hours. MMP-13 mRNA expression was reduced after the incubation with AA 20 and 60 μg/ml (inhibitor of complex III) and Oligomycin. Results were validated at protein level observing an increase in the intracellular levels of MMP-1 and -3 after Oligomycin 25 μg/ml stimulation [(15.20±8.46 and 4.59±1.83 vs. basal=1, respectively (n=4; *P<0.05)]. However, AA and Oligomycin reduced the intracellular levels of the MMP-13 protein (0.70±0.16 and 0.3±0.24, respectively vs. basal=1). In order to know whether the

  14. Improving the quality of discharge summaries: implementing updated Academy of Medical Royal Colleges standards at a district general hospital.

    PubMed

    May-Miller, Hannah; Hayter, Joanne; Loewenthal, Lola; Hall, Louis; Hilbert, Rebecca; Quinn, Michael; Pearson, Nicola; Patel, Alisha; Law, Rebekah

    2015-01-01

    Quality of documentation is harder to quantify and incentivise, but it has a significant impact on patient care. Good discharge summaries facilitate continuity between secondary and primary care. The junior doctors' forum led this project to improve the quality of electronic discharge summaries (eDS). Baseline measurement revealed significant room for improvement. We measured the quality of 10 summaries per month (across all inpatient specialties), against 23 indicators from the revised Academy of Medical Royal Colleges (AoMRC) standards (2013) that were prioritised by GPs as a "minimum dataset". Junior doctors felt that the Trust's dual eDS systems were responsible for great variation in quality. This was confirmed by the results of a comparison audit of the systems in April 2014: one system greatly outperformed the other (57% mean compliance with iSoft clinical management (iCM) based system vs. 77% with InfoPath-based system). We recommended that the Trust move to a single eDS system, decommissioning the iCM-based system, and this proposal was approved by several Trust committees. We worked with information services, junior doctors, general practitioners and hospital physicians to develop and implement a generic template to further improve compliance with AoMRC standards. In August 2014, the iCM-based system was withdrawn, the new template went live, and training was delivered, coinciding with the changeover of junior doctors to minimise disruption. Median compliance increased from 66.7% to 77.8%. Quality of discharge summaries had improved across the specialties. There was a reduction in the number of complaints and positive qualitative feedback from general practitioners and junior doctors. Completion of discharge summaries within 24 hours was not affected by this change. There is still more to be done to improve quality; average compliance with the full AoMRC standards (39 indicators) is 59.5%. With the approval of the Trust executive committee further plan

  15. Sulfolipo-cyclodextrin in squalane-in-water as a novel and safe vaccine adjuvant.

    PubMed

    Hilgers, L A; Lejeune, G; Nicolas, I; Fochesato, M; Boon, B

    1999-01-21

    Previously, we described synergistic adjuvanticity of combinations of synthetic sulfolipo(SL)-derivatives of polysaccharide (SL-polysaccharides) and squalane-in-water emulsions (squalane/W). In this paper, effects of type of polysaccharide and nature of oil on adjuvanticity, reactogenicity and stability are described. SL-derivatives of the following polysaccharides were synthesised: synthetic polysucroses with weight-average molecular weight (MW) of 400,000 (Ficoll400), 70,000 (Ficoll70) and 39,000 Da (Ficoll39), polyfructose of 5,000 Da (inulin), linear polyglucose of 1,200 Da (maltodextrin) and cyclic polyglucose of 1,135 Da (beta-cyclodextrin). The number of sulphate groups per monosaccharide of the different SL-polysaccharides varied between 0.15 and 0.23 and the number of lipid groups per monosaccharide between 1.15 and 1.29. Adjuvant formulations were prepared by incorporating these SL-polysaccharides into oil-in-water emulsions of either squalane, hexadecane, soya oil or mineral oil. Adjuvanticity of the formulations obtained for humoral responses to inactivated pseudorabies virus (PRV) and inactivated influenza virus strains A/Swine (A/Swine) and MRC-11 (MRC-11) in pigs and MRC-11 and ovalbumin (OVA) in mice depended on the type of oil (squalane = mineral oil > hexadecane = soya oil) but not on the type of polysaccharide backbone of the SL-derivative. Reactogenicity assessed by local swelling in mice decreased with decreasing MW (SL-Ficoll400 = Ficoll70 = Ficoll39 > SL-inulin = SL-maltodextrin > SL-cyclodextrin) when combined with squalane and decreased with the type of oil in the following order: squalane > mineral oil > hexadecane > soya oil when combined with SL-Ficoll400. Stability of the SL-polysaccharide/squalane/W emulsions at elevated temperature increased with decreasing MW of the SL-polysaccharide (SL-Ficoll400 < SL-Ficoll70 = SL-Ficoll39 < SL-inulin = SL-maltodextrin = SL-cyclodextrin). SL-cyclodextrin/squalane/W remained stable for > 2.5 years

  16. COPD exacerbations associated with the modified Medical Research Council scale and COPD assessment test among Humana Medicare members

    PubMed Central

    Pasquale, Margaret K; Xu, Yihua; Baker, Christine L; Zou, Kelly H; Teeter, John G; Renda, Andrew M; Davis, Cralen C; Lee, Theodore C; Bobula, Joel

    2016-01-01

    Background The Global initiative for chronic Obstructive Lung Disease guidelines recommend assessment of COPD severity, which includes symptomatology using the modified Medical Research Council (mMRC) or COPD assessment test (CAT) score in addition to the degree of airflow obstruction and exacerbation history. While there is great interest in incorporating symptomatology, little is known about how patient reported symptoms are associated with future exacerbations and exacerbation-related costs. Methods The mMRC and CAT were mailed to a randomly selected sample of 4,000 Medicare members aged >40 years, diagnosed with COPD (≥2 encounters with International Classification of Dis eases-9th Edition Clinical Modification: 491.xx, 492.xx, 496.xx, ≥30 days apart). The exacerbations and exacerbation-related costs were collected from claims data during 365-day post-survey after exclusion of members lost to follow-up or with cancer, organ transplant, or pregnancy. A logistic regression model estimated the predictive value of exacerbation history and symptomatology on exacerbations during follow-up, and a generalized linear model with log link and gamma distribution estimated the predictive value of exacerbation history and symptomatology on exacerbation-related costs. Results Among a total of 1,159 members who returned the survey, a 66% (765) completion rate was observed. Mean (standard deviation) age among survey completers was 72.0 (8.3), 53.7% female and 91.2% white. Odds ratios for having post-index exacerbations were 3.06, 4.55, and 16.28 times for members with 1, 2, and ≥3 pre-index exacerbations, respectively, relative to members with 0 pre-index exacerbations (P<0.001 for all). The odds ratio for high vs low symptoms using CAT was 2.51 (P<0.001). Similarly, exacerbation-related costs were 73% higher with each incremental pre-index exacerbation, and over four fold higher for high-vs low-symptom patients using CAT (each P<0.001). The symptoms using mMRC were not

  17. Effectiveness of pulmonary rehabilitation in COPD with mild symptoms: a systematic review with meta-analyses

    PubMed Central

    Rugbjerg, Mette; Iepsen, Ulrik Winning; Jørgensen, Karsten Juhl; Lange, Peter

    2015-01-01

    Purpose Most guidelines recommend pulmonary rehabilitation (PR) for patients with chronic obstructive pulmonary disease (COPD) and modified Medical Research Council dyspnea scale (mMRC) levels ≥2, but the effectiveness of PR in patients with less advanced disease is not well established. Our aim was to investigate the effects of PR in patients with COPD and mMRC ≤1. Methods The methodology was developed as a part of evidence-based guideline development and is in accordance with the principles of the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group. We identified randomized controlled trials (RCTs) through a systematic, multidatabase literature search and selected RCTs comparing the effects of PR with usual care in patients with COPD and mMRC ≤1. Predefined critical outcomes were health-related quality of life (HRQoL), adverse effects and mortality, while walking distance, maximal exercise capacity, muscle strength, and dropouts were important outcomes. Two authors independently extracted data, assessed trial eligibility and risk of bias, and graded the evidence. Meta-analyses were performed when deemed feasible. Results Four RCTs (489 participants) were included. On the basis of moderate-quality evidence, we found a clinically and statistically significant improvement in short-term HRQoL of 4.2 units (95% confidence interval [CI]: [−4.51 to −3.89]) on St George’s Respiratory Questionnaire, but not at the longest follow-up. We also found a statistically significant improvement of 25.71 m (95% CI: [15.76–35.65]) in the 6-minute walk test with PR; however, this improvement was not considered clinically relevant. No difference was found for mortality, and insufficient data prohibited meta-analysis for muscle strength and maximal exercise capacity. No adverse effects were reported. Conclusion We found a moderate quality of evidence suggesting a small, significant improvement in short-term HRQoL and a clinically

  18. Diagnosis and management of choledocholithiasis in the golden age of imaging, endoscopy and laparoscopy

    PubMed Central

    Costi, Renato; Gnocchi, Alessandro; Di Mario, Francesco; Sarli, Leopoldo

    2014-01-01

    Biliary lithiasis is an endemic condition in both Western and Eastern countries, in some studies affecting 20% of the general population. In up to 20% of cases, gallbladder stones are associated with common bile duct stones (CBDS), which are asymptomatic in up to one half of cases. Despite the wide variety of examinations and techniques available nowadays, two main open issues remain without a clear answer: how to cost-effectively diagnose CBDS and, when they are finally found, how to deal with them. CBDS diagnosis and management has radically changed over the last 30 years, following the dramatic diffusion of imaging, including endoscopic ultrasound (EUS) and magnetic resonance cholangiography (MRC), endoscopy and laparoscopy. Since accuracy, invasiveness, potential therapeutic use and cost-effectiveness of imaging techniques used to identify CBDS increase together in a parallel way, the concept of “risk of carrying CBDS” has become pivotal to identifying the most appropriate management of a specific patient in order to avoid the risk of “under-studying” by poor diagnostic work up or “over-studying” by excessively invasive examinations. The risk of carrying CBDS is deduced by symptoms, liver/pancreas serology and ultrasound. “Low risk” patients do not require further examination before laparoscopic cholecystectomy. Two main “philosophical approaches” face each other for patients with an “intermediate to high risk” of carrying CBDS: on one hand, the “laparoscopy-first” approach, which mainly relies on intraoperative cholangiography for diagnosis and laparoscopic common bile duct exploration for treatment, and, on the other hand, the “endoscopy-first” attitude, variously referring to MRC, EUS and/or endoscopic retrograde cholangiography for diagnosis and endoscopic sphincterotomy for management. Concerning CBDS diagnosis, intraoperative cholangiography, EUS and MRC are reported to have similar results. Regarding management, the recent

  19. Antiviral Activity and Possible Mechanism of Action of Constituents Identified in Paeonia lactiflora Root toward Human Rhinoviruses

    PubMed Central

    Ngan, Luong Thi My; Jang, Myeong Jin; Kwon, Min Jung; Ahn, Young Joon

    2015-01-01

    Human rhinoviruses (HRVs) are responsible for more than half of all cases of the common cold and cost billions of USD annually in medical visits and missed school and work. An assessment was made of the antiviral activities and mechanisms of action of paeonol (PA) and 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) from Paeonia lactiflora root toward HRV-2 and HRV-4 in MRC5 cells using a tetrazolium method and real-time quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Results were compared with those of a reference control ribavirin. Based on 50% inhibitory concentration values, PGG was 13.4 and 18.0 times more active toward HRV-2 (17.89 μM) and HRV-4 (17.33 μM) in MRC5 cells, respectively, than ribavirin. The constituents had relatively high selective index values (3.3–>8.5). The 100 μg/mL PA and 20 μg/mL PGG did not interact with the HRV-4 particles. These constituents inhibited HRV-4 infection only when they were added during the virus inoculation (0 h), the adsorption period of HRVs, but not after 1 h or later. Moreover, the RNA replication levels of HRVs were remarkably reduced in the MRC5 cultures treated with these constituents. These findings suggest that PGG and PA may block or reduce the entry of the viruses into the cells to protect the cells from the virus destruction and abate virus replication, which may play an important role in interfering with expressions of rhinovirus receptors (intercellular adhesion molecule-1 and low-density lipoprotein receptor), inflammatory cytokines (interleukin (IL)-6, IL-8, tumor necrosis factor, interferon beta, and IL-1β), and Toll-like receptor, which resulted in diminishing symptoms induced by HRV. Global efforts to reduce the level of synthetic drugs justify further studies on P. lactiflora root-derived materials as potential anti-HRV products or lead molecules for the prevention or treatment of HRV. PMID:25860871

  20. The liquorice root derivative glycyrrhetinic acid can ameliorate ionoregulatory disturbance in rainbow trout (Oncorhynchus mykiss) abruptly exposed to ion-poor water.

    PubMed

    Chen, Chun Chih; Kolosov, Dennis; Kelly, Scott P

    2016-09-01

    To consider the idea that a dietary botanical supplement could act as an adaptogen in a teleost fish, the effect of a liquorice root derivative (18β-glycyrrhetinic acid, 18βGA) on rainbow trout following an acute ionoregulatory stressor was examined. Freshwater (FW) trout were fed a control or 18βGA supplemented diet (0, 5, or 50μg 18βGA/g diet) for 2weeks, then abruptly exposed to ion-poor water (IPW) for 24h. Following IPW exposure, muscle moisture content and serum cortisol levels elevated and serum [Na(+)] and/or [Cl(-)] reduced in control and 50μg/g 18βGA-fed fish. However, these endpoints were unaltered in 5μg/g 18βGA-fed fish. Gill tissue was investigated for potential mechanisms of 18βGA action by examining mRNA abundance of genes encoding corticosteroid receptors (CRs), 11β-hydroxysteroid dehydrogenase 2 (11β-hsd2), and tight junction (TJ) proteins, as well as Na(+)-K(+)-ATPase and H(+)-ATPase activity, and mitochondrion-rich cell (MRC) morphometrics. Following IPW exposure, CR and 11β-hsd2 mRNA, MRC fractional surface, Na(+)-K(+)-ATPase and H(+)-ATPase activity were unaltered or decreased in 50μg 18βGA fish, as was mRNA encoding select TJ proteins. In contrast, 5μg 18βGA-fed fish exhibited elevated 11β-hsd2 and CR mRNA abundance versus 50μg 18βGA-fed, and reduced MRC apical area as well as some differences in TJ protein mRNA abundance versus control fish. Data suggest that 18βGA, at low levels, may be adaptogenic in trout and might help to ameliorate ionoregulatory perturbation following IPW exposure. This seems to occur, in part, through 18βGA-induced alterations in the biochemistry and physiology of the gill.

  1. dNTP pool levels modulate mutator phenotypes of error-prone DNA polymerase ε variants

    PubMed Central

    Williams, Lindsey N.; Marjavaara, Lisette; Knowels, Gary M.; Schultz, Eric M.; Fox, Edward J.; Chabes, Andrei; Herr, Alan J.

    2015-01-01

    Mutator phenotypes create genetic diversity that fuels tumor evolution. DNA polymerase (Pol) ε mediates leading strand DNA replication. Proofreading defects in this enzyme drive a number of human malignancies. Here, using budding yeast, we show that mutator variants of Pol ε depend on damage uninducible (Dun)1, an S-phase checkpoint kinase that maintains dNTP levels during a normal cell cycle and up-regulates dNTP synthesis upon checkpoint activation. Deletion of DUN1 (dun1Δ) suppresses the mutator phenotype of pol2-4 (encoding Pol ε proofreading deficiency) and is synthetically lethal with pol2-M644G (encoding altered Pol ε base selectivity). Although pol2-4 cells cycle normally, pol2-M644G cells progress slowly through S-phase. The pol2-M644G cells tolerate deletions of mediator of the replication checkpoint (MRC) 1 (mrc1Δ) and radiation sensitive (Rad) 9 (rad9Δ), which encode mediators of checkpoint responses to replication stress and DNA damage, respectively. The pol2-M644G mutator phenotype is partially suppressed by mrc1Δ but not rad9Δ; neither deletion suppresses the pol2-4 mutator phenotype. Thus, checkpoint activation augments the Dun1 effect on replication fidelity but is not required for it. Deletions of genes encoding key Dun1 targets that negatively regulate dNTP synthesis, suppress the dun1Δ pol2-M644G synthetic lethality and restore the mutator phenotype of pol2-4 in dun1Δ cells. DUN1 pol2-M644G cells have constitutively high dNTP levels, consistent with checkpoint activation. In contrast, pol2-4 and POL2 cells have similar dNTP levels, which decline in the absence of Dun1 and rise in the absence of the negative regulators of dNTP synthesis. Thus, dNTP pool levels correlate with Pol ε mutator severity, suggesting that treatments targeting dNTP pools could modulate mutator phenotypes for therapy. PMID:25827226

  2. dNTP pool levels modulate mutator phenotypes of error-prone DNA polymerase ε variants.

    PubMed

    Williams, Lindsey N; Marjavaara, Lisette; Knowels, Gary M; Schultz, Eric M; Fox, Edward J; Chabes, Andrei; Herr, Alan J

    2015-05-12

    Mutator phenotypes create genetic diversity that fuels tumor evolution. DNA polymerase (Pol) ε mediates leading strand DNA replication. Proofreading defects in this enzyme drive a number of human malignancies. Here, using budding yeast, we show that mutator variants of Pol ε depend on damage uninducible (Dun)1, an S-phase checkpoint kinase that maintains dNTP levels during a normal cell cycle and up-regulates dNTP synthesis upon checkpoint activation. Deletion of DUN1 (dun1Δ) suppresses the mutator phenotype of pol2-4 (encoding Pol ε proofreading deficiency) and is synthetically lethal with pol2-M644G (encoding altered Pol ε base selectivity). Although pol2-4 cells cycle normally, pol2-M644G cells progress slowly through S-phase. The pol2-M644G cells tolerate deletions of mediator of the replication checkpoint (MRC) 1 (mrc1Δ) and radiation sensitive (Rad) 9 (rad9Δ), which encode mediators of checkpoint responses to replication stress and DNA damage, respectively. The pol2-M644G mutator phenotype is partially suppressed by mrc1Δ but not rad9Δ; neither deletion suppresses the pol2-4 mutator phenotype. Thus, checkpoint activation augments the Dun1 effect on replication fidelity but is not required for it. Deletions of genes encoding key Dun1 targets that negatively regulate dNTP synthesis, suppress the dun1Δ pol2-M644G synthetic lethality and restore the mutator phenotype of pol2-4 in dun1Δ cells. DUN1 pol2-M644G cells have constitutively high dNTP levels, consistent with checkpoint activation. In contrast, pol2-4 and POL2 cells have similar dNTP levels, which decline in the absence of Dun1 and rise in the absence of the negative regulators of dNTP synthesis. Thus, dNTP pool levels correlate with Pol ε mutator severity, suggesting that treatments targeting dNTP pools could modulate mutator phenotypes for therapy.

  3. Implications of the GOLD 2011 Disease Severity Classification in the COPDGene Cohort

    PubMed Central

    Han, MeiLan K.; Muellerova, Hana; Curran-Everett, Douglas; Dransfield, Mark; Washko, George; Regan, Elizabeth A.; Bowler, Russell; Beaty, Terri H.; Hokanson, John E.; Lynch, David; Jones, Paul; Anzueto, Antonio; Martinez, Fernando J.; Crapo, James; Silverman, Edwin K.; Make, Barry

    2014-01-01

    Background The 2011 Global Strategy for the Diagnosis, Management, and Prevention of COPD (GOLD) consensus report uses symptoms, exacerbation history and FEV1% to define four categories: A, low symptoms/low risk; B, high symptoms/low risk; C, low symptoms/high risk; and D, high symptoms/high risk where risk refers to exacerbations, hospitalization and death. Our objective was to determine (1) the influence of symptom instrument on category membership and (2) prospective exacerbation risk by category. Methods 4,484 COPD subjects from COPDGene were analyzed. All subjects had smoking history ≥ 10 pack-years and FEV1/FVC<0·7. Categories were defined using the modified Medical Research Council Dyspnea [mMRC] (0–1 versus ≥ 2) and the Saint George’s Respiratory Questionnaire [SGRQ] (≥25 versus <25 as a surrogate for the COPD Assessment Test ≥ 10 versus <10) in addition to COPD exacerbations in the prior year (<2 versus ≥ 2), and FEV1% predicted (≥50 versus <50). Findings Category assignment using mMRC versus SGRQ were similar but not identical. Using the mMRC, category assignments were 34% A, 21% B, 8% C and 38% D and for SGRQ were 29% A, 25% B, 5% C and 41% D (kappa=0·77). Significant heterogeneity in exacerbation rates (exacerbations/person-year) were seen particularly within the D group, depending on the risk factor that determined category assignment (lung function (0·89), prior exacerbation history (1·34) or both (1·86), p<0·001. Interpretations The GOLD classification emphasizes the importance of symptoms and exacerbation risk in assessing COPD severity. The choice of symptom measure influences category assignment. The relative number of subjects with low symptoms and high risk for exacerbations (category C) is low. Differences in exacerbation rates for subjects in the highest risk category D were seen depending on whether risk was based on lung function, exacerbation history or both. PMID:24321803

  4. Prognostic Importance of Dyspnea for Cardiovascular Outcomes and Mortality in Persons without Prevalent Cardiopulmonary Disease: The Atherosclerosis Risk in Communities Study

    PubMed Central

    Santos, Mario; Kitzman, Dalane W.; Matsushita, Kunihiro; Loehr, Laura; Sueta, Carla A.; Shah, Amil M.

    2016-01-01

    Background The relationship between dyspnea and incident heart failure (HF) and myocardial infarction (MI) among patients without previously diagnosed cardiopulmonary disease is unclear. We studied the prognostic relevance of self-reported dyspnea for cardiovascular outcomes and all-cause mortality in persons without previously diagnosed cardiopulmonary disease. Methods and Results We studied 10 881 community-dwelling participants (mean age 57±6, 56% women, 25% black) who were free of prevalent cardiopulmonary disease from Atherosclerosis Risk in Communities Study. Dyspnea status at study entry using the modified Medical Research Council (mMRC) scale. The primary outcomes were time to HF, MI or all-cause death. Dyspnea prevalence was 22%, and was mild (mMRC grade 1 or 2) in 21% and moderate-to-severe (mMRC 3 or 4) in 1%. The main correlates of dyspnea were older age, female sex, higher BMI and active smoking. Over a follow-up of 19±5 years, greater self-reported dyspnea severity was associated with worse prognosis. Mild dyspnea was associated with significantly heightened risk of HF (adjusted Hazard Ratio, HR,1.30; 95% CI: 1.16–1.46), MI (adjusted HR 1.34; 95%CI: 1.20–1.50), and death (adjusted HR 1.16; 95%CI: 1.06–1.26), with moderate/severe dyspnea associated with an even greater risk (adjusted HR 2.14, 95%CI: 1.59–2.89; 1.93, 95%CI: 1.41–2.56; 1.96, 95%CI: 1.55–2.48, respectively). Conclusion In community-dwelling persons free of previously diagnosed cardiopulmonary disease, self-reported dyspnea is common and, even when of mild intensity, it is independently associated with a greater risk of incident HF, MI, and death. Our data emphasize the prognostic importance of even mild self-reported dyspnea for cardiovascular outcomes. PMID:27780208

  5. Analysis of the biological response of endothelial and fibroblast cells cultured on synthetic scaffolds with various hydrophilic/hydrophobic ratios: influence of fibronectin adsorption and conformation.

    PubMed

    Campillo-Fernández, Alberto J; Unger, Ronald E; Peters, Kirsten; Halstenberg, Sven; Santos, Marina; Salmerón Sánchez, Manuel; Meseguer Dueñas, Jose Maria; Monleón Pradas, Manuel; Gómez Ribelles, Jose Luis; Kirkpatrick, C James

    2009-06-01

    In this study we developed polymer scaffolds intended as anchorage rings for cornea prostheses among other applications, and examined their cell compatibility. In particular, a series of interconnected porous polymer scaffolds with pore sizes from 80 to 110 microns were manufactured varying the ratio of hydrophobic to hydrophilic monomeric units along the polymer chains. Further, the effects of fibronectin precoating, a physiological adhesion molecule, were tested. The interactions between the normal human fibroblast cell line MRC-5 and primary human umbilical vein endothelial cells (HUVECs) with the scaffold surfaces were evaluated. Adhesion and growth of the cells was examined by confocal laser scanning microscopy. Whereas MRC-5 fibroblasts showed adhesion and spreading to the scaffolds without any precoating, HUVECs required a fibronectin precoating for adhesion and spreading. Although both cell types attached and spread on scaffold surfaces with a content of up to a 20% hydrophilic monomers, cell adhesion, spreading, and proliferation increased with increasing hydrophobicity of the substrate. This effect is likely due to better adsorption of serum proteins to hydrophobic substrates, which then facilitate cell adhesion. In fact, atomic force microscopy measurements of fibronectin on surfaces representative of our scaffolds revealed that the amount of fibronectin adsorption correlated directly with the hydrophobicity of the surface. Besides cell adhesion we also examined the inflammatory state of HUVECs in contact with the scaffolds. Typical patterns of platelet/endothelial cell adhesion molecule-1 expression were observed at intercellular boarders. HUVECs adhering on the scaffolds retained their proinflammatory response potential as shown by E-selectin mRNA expression after stimulation with lipopolyssacharide (LPS). The proinflammatory activation occurred in most of the cells, thus confirming the presence of a functionally intact endothelium. Little or no

  6. ALMA finds dew drops in the dusty spider's web

    NASA Astrophysics Data System (ADS)

    Gullberg, Bitten; Lehnert, Matthew D.; De Breuck, Carlos; Branchu, Steve; Dannerbauer, Helmut; Drouart, Guillaume; Emonts, Bjorn; Guillard, Pierre; Hatch, Nina; Nesvadba, Nicole P. H.; Omont, Alain; Seymour, Nick; Vernet, Joël

    2016-06-01

    We present 0.̋5 resolution ALMA detections of the observed 246 GHz continuum, [CI] 3P2→3P1 fine structure line ([CI]2-1), CO(7-6), and H2O lines in the z = 2.161 radio galaxy MRC1138-262, the so-called Spiderweb galaxy. We detect strong [CI]2-1 emission both at the position of the radio core, and in a second component ~4 kpc away from it. The 1100 km s-1 broad [CI]2-1 line in this latter component, combined with its H2 mass of 1.6 × 1010 M⊙, implies that this emission must come from a compact region <60 pc, possibly containing a second active galactic nucleus (AGN). The combined H2 mass derived for both objects, using the [CI]2-1 emission, is 3.3 × 1010 M⊙. The total CO(7-6)/[CI]2-1 line flux ratio of 0.2 suggests a low excitation molecular gas reservoir and/or enhanced atomic carbon in cosmic ray dominated regions. We detect spatially-resolved H2O 211-202 emission - for the first time in a high-z unlensed galaxy - near the outer radio lobe to the east, and near the bend of the radio jet to the west of the radio galaxy. No underlying 246 GHz continuum emission is seen at either position. We suggest that the H2O emission is excited in the cooling region behind slow (10-40 km s-1) shocks in dense molecular gas (103-5 cm-3). The extended water emission is likely evidence of the radio jet's impact on cooling and forming molecules in the post-shocked gas in the halo and inter-cluster gas, similar to what is seen in low-z clusters and other high-z radio galaxies. These observations imply that the passage of the radio jet in the interstellar and inter-cluster medium not only heats gas to high temperatures, as is commonly assumed or found in simulations, but also induces cooling and dissipation, which can lead to substantial amounts of cold dense molecular gas. The formation of molecules and strong dissipation in the halo gas of MRC1138-262 may explain both the extended diffuse molecular gas and the young stars observed around MRC1138-262. The reduced data cubes

  7. Theory of fluorescence intermittency in quantum dots and other fluorophores

    NASA Astrophysics Data System (ADS)

    Volkan-Kacso, Sandor

    2011-12-01

    The purpose of the dissertation is to provide a theoretical explanation to the phenomenon of fluorescence intermittency. This is achieved by proposing a model of Multiple Recombination Centers (MRC), which is shown to successfully reproduce the main features of the phenomenon. Virtually all known types of optically active nanoscale objects to date show extremely long correlations in the fluctuations of fluorescence intensity. Experimentally collected intensity trajectories from such single fluorophores show fluctuations on the timescales longer than seconds. This phenomenon is generically referred to as fluorescence intermittency or blinking. In colloidal quantum dots blinking often assumes the shape of a random telegraph-like intermittency, a stochastic series of "ON" and "OFF" time intervals. Amazingly, the distribution of these ON and OFF times follow a universal power law dependence. Spectral characterization of trajectories effectively renders blinking an optical 1/f type noise. By a suitable Bayesian estimation method we point out that the conventional method of analysis using intensity histograms is problematic for such trajectories: The qualitative properties of the distributions strongly depend on the threshold value chosen for the separation the ON and OFF states. We propose phenomenological MRC model for the quantum dot and its environment by modeling the multiple channels of non-radiative relaxation as a collection of a few interacting two-level systems. We show how this model of multiple recombination centers reproduces key experimental features of blinking, including the strong threshold dependence. After a survey of existing models of blinking, we show that the MRC model is the only self-consistent model that can explain the long-range correlations found between blinking times. Beyond quantum dots, a carefully performed spectral analysis of intensity fluctuations observed in other fluorophores such as self-assembled quantum dots, nanorods, nanowires

  8. Brief of the Canadian Society for Clinical Investigation to the science and technology review.

    PubMed

    1995-02-01

    In the context of new realities, perceptions, and concerns, it is fitting that the government has undertaken this Science and Technology Review, questioning not only how much to spend but also the justification and the best ways to carry out federally-funded research. We share the government's concern about the lack of economic competitiveness of our industries and agree that government-sponsored research should make a bigger contribution to the nation's global economic position. The CSCI, which represents the clinical investigators/scientists in this country, is grateful for having been given the opportunity to make this "tour d'horizon" of Canadian clinical research. In this brief, we have attempted to articulate the needs for, and the benefits of, basic biomedical research because it is the only type of research which will provide us with final answers. However, it should be more closely articulated with applied research, as well as with epidemiological, evaluative, and operational approaches which have been neglected. This brief has emphasized that CSCI is committed to PUTTING MORE SCIENCE INTO MEDICINE by encouraging a greater flow of discoveries from the laboratory research bench to the bedside and the community. We made the point that there is a crisis in patient-oriented research and a decrease of young physicians opting for research careers. The Royal College of Physicians and Surgeons of Canada and the MRC are responsive to this situation, which may compromise our capacity to discharge our broader mission. The MRC has given itself valid instruments to foster the creation of wealth through special programs such as the NCE, the University/Industry program, and the MRC-PMAC partnership. Some refining is in order, and close scrutiny of outcome is essential. Both the academic community and industry have their share of responsibility for the less-than-optimal transfer of knowledge to the market place. Lack of venture capital is also a serious issue. A unified

  9. Brief of the Canadian Society for Clinical Investigation to the science and technology review.

    PubMed

    1995-02-01

    In the context of new realities, perceptions, and concerns, it is fitting that the government has undertaken this Science and Technology Review, questioning not only how much to spend but also the justification and the best ways to carry out federally-funded research. We share the government's concern about the lack of economic competitiveness of our industries and agree that government-sponsored research should make a bigger contribution to the nation's global economic position. The CSCI, which represents the clinical investigators/scientists in this country, is grateful for having been given the opportunity to make this "tour d'horizon" of Canadian clinical research. In this brief, we have attempted to articulate the needs for, and the benefits of, basic biomedical research because it is the only type of research which will provide us with final answers. However, it should be more closely articulated with applied research, as well as with epidemiological, evaluative, and operational approaches which have been neglected. This brief has emphasized that CSCI is committed to PUTTING MORE SCIENCE INTO MEDICINE by encouraging a greater flow of discoveries from the laboratory research bench to the bedside and the community. We made the point that there is a crisis in patient-oriented research and a decrease of young physicians opting for research careers. The Royal College of Physicians and Surgeons of Canada and the MRC are responsive to this situation, which may compromise our capacity to discharge our broader mission. The MRC has given itself valid instruments to foster the creation of wealth through special programs such as the NCE, the University/Industry program, and the MRC-PMAC partnership. Some refining is in order, and close scrutiny of outcome is essential. Both the academic community and industry have their share of responsibility for the less-than-optimal transfer of knowledge to the market place. Lack of venture capital is also a serious issue. A unified

  10. Antiviral activity and possible mechanism of action of constituents identified in Paeonia lactiflora root toward human rhinoviruses.

    PubMed

    Ngan, Luong Thi My; Jang, Myeong Jin; Kwon, Min Jung; Ahn, Young Joon

    2015-01-01

    Human rhinoviruses (HRVs) are responsible for more than half of all cases of the common cold and cost billions of USD annually in medical visits and missed school and work. An assessment was made of the antiviral activities and mechanisms of action of paeonol (PA) and 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) from Paeonia lactiflora root toward HRV-2 and HRV-4 in MRC5 cells using a tetrazolium method and real-time quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Results were compared with those of a reference control ribavirin. Based on 50% inhibitory concentration values, PGG was 13.4 and 18.0 times more active toward HRV-2 (17.89 μM) and HRV-4 (17.33 μM) in MRC5 cells, respectively, than ribavirin. The constituents had relatively high selective index values (3.3->8.5). The 100 μg/mL PA and 20 μg/mL PGG did not interact with the HRV-4 particles. These constituents inhibited HRV-4 infection only when they were added during the virus inoculation (0 h), the adsorption period of HRVs, but not after 1 h or later. Moreover, the RNA replication levels of HRVs were remarkably reduced in the MRC5 cultures treated with these constituents. These findings suggest that PGG and PA may block or reduce the entry of the viruses into the cells to protect the cells from the virus destruction and abate virus replication, which may play an important role in interfering with expressions of rhinovirus receptors (intercellular adhesion molecule-1 and low-density lipoprotein receptor), inflammatory cytokines (interleukin (IL)-6, IL-8, tumor necrosis factor, interferon beta, and IL-1β), and Toll-like receptor, which resulted in diminishing symptoms induced by HRV. Global efforts to reduce the level of synthetic drugs justify further studies on P. lactiflora root-derived materials as potential anti-HRV products or lead molecules for the prevention or treatment of HRV. PMID:25860871

  11. Assessment of Impact on Students and Teachers of Student-led, inquiry-based planetary science instruction in Grades 3-8

    NASA Astrophysics Data System (ADS)

    Bering, Edgar Andrew; Carlson, Coleen; Nieser, Kenneth; Slagle, Elana

    2015-11-01

    The University of Houston is in the process of developing a flexible program that offers children an in-depth educational experience culminating in the design and construction of their own model Mars rover. The program is called the Mars Rover Model Celebration (MRC). It focuses on students, teachers and parents in grades 3-8. Students design and build a model of a Mars rover to carry out a student selected science mission on the surface of Mars. A total of 195 Mars Rover teachers from the 2012-2013, 2013-2014, and 2014-2015 cohorts were invited to complete the Mars Rover Teacher Evaluation Survey. The survey was administered online and could be taken at the convenience of the participant. So far ~90 teachers have participated with responses still coming in. A total of 1300 students from the 2013-2014 and 2014-2015 cohort were invited to submit brief self-assessments of their participation in the program. Teachers were asked to rate their current level of confidence in their ability to teach specific topics within the Earth and Life Science realms, as well as their confidence in their ability to implement teaching strategies with their students. The most striking increase in this area was the reported 48% of teachers who felt their confidence in teaching “Earth and the solar system and universe” increased “Quite a bit” as a result of their participation in the MRC program. The vast majority of teachers (86-100%) felt somewhat to very confident in their ability to effectively implement all of the listed teaching strategies. The most striking increases were the percentage of teachers who felt their confidence increased “Quite a bit” as a result of their participation in the MRC program in the following areas: “Getting students interested in and curious about science” (63%); “Teaching science as a co-inquirer with students” (56%); and “Continually find better ways to teach science” (59%). Student outcome analysis is pending correlation with

  12. Human Cytomegalovirus Exploits Interferon-Induced Transmembrane Proteins To Facilitate Morphogenesis of the Virion Assembly Compartment

    PubMed Central

    Xie, Maorong; Xuan, Baoqin; Shan, Jiaoyu; Pan, Deng; Sun, Yamei; Shan, Zhao; Zhang, Jinping; Yu, Dong

    2014-01-01

    ABSTRACT Recently, interferon-induced transmembrane proteins (IFITMs) have been identified to be key effector molecules in the host type I interferon defense system. The invasion of host cells by a large range of RNA viruses is inhibited by IFITMs during the entry step. However, the roles of IFITMs in DNA virus infections have not been studied in detail. In this study, we report that human cytomegalovirus (HCMV), a large human DNA virus, exploits IFITMs to facilitate the formation of the virion assembly compartment (vAC) during infection of human fibroblasts. We found that IFITMs were expressed constitutively in human embryonic lung fibroblasts (MRC5 cells). HCMV infection inhibited IFITM protein accumulation in the later stages of infection. Overexpression of an IFITM protein in MRC5 cells slightly enhanced HCMV production and knockdown of IFITMs by RNA interference reduced the virus titer by about 100-fold on day 8 postinfection, according to the findings of a virus yield assay at a low multiplicity of infection. Virus gene expression and DNA synthesis were not affected, but the typical round structure of the vAC was not formed after the suppression of IFITMs, thereby resulting in defective virion assembly and the production of less infectious virion particles. Interestingly, the replication of herpes simplex virus, a human herpesvirus that is closely related to HCMV, was not affected by the suppression of IFITMs in MRC5 cells. These results indicate that IFITMs are involved in a specific pathway required for HCMV replication. IMPORTANCE HCMV is known to repurpose the interferon-stimulated genes (ISGs) viperin and tetherin to facilitate its replication. Our results expand the range of ISGs that can be exploited by HCMV for its replication. This is also the first report of a proviral function of IFITMs in DNA virus replication. In addition, whereas previous studies showed that IFITMs modulate virus entry, which is a very early stage in the virus life cycle, we

  13. The liquorice root derivative glycyrrhetinic acid can ameliorate ionoregulatory disturbance in rainbow trout (Oncorhynchus mykiss) abruptly exposed to ion-poor water.

    PubMed

    Chen, Chun Chih; Kolosov, Dennis; Kelly, Scott P

    2016-09-01

    To consider the idea that a dietary botanical supplement could act as an adaptogen in a teleost fish, the effect of a liquorice root derivative (18β-glycyrrhetinic acid, 18βGA) on rainbow trout following an acute ionoregulatory stressor was examined. Freshwater (FW) trout were fed a control or 18βGA supplemented diet (0, 5, or 50μg 18βGA/g diet) for 2weeks, then abruptly exposed to ion-poor water (IPW) for 24h. Following IPW exposure, muscle moisture content and serum cortisol levels elevated and serum [Na(+)] and/or [Cl(-)] reduced in control and 50μg/g 18βGA-fed fish. However, these endpoints were unaltered in 5μg/g 18βGA-fed fish. Gill tissue was investigated for potential mechanisms of 18βGA action by examining mRNA abundance of genes encoding corticosteroid receptors (CRs), 11β-hydroxysteroid dehydrogenase 2 (11β-hsd2), and tight junction (TJ) proteins, as well as Na(+)-K(+)-ATPase and H(+)-ATPase activity, and mitochondrion-rich cell (MRC) morphometrics. Following IPW exposure, CR and 11β-hsd2 mRNA, MRC fractional surface, Na(+)-K(+)-ATPase and H(+)-ATPase activity were unaltered or decreased in 50μg 18βGA fish, as was mRNA encoding select TJ proteins. In contrast, 5μg 18βGA-fed fish exhibited elevated 11β-hsd2 and CR mRNA abundance versus 50μg 18βGA-fed, and reduced MRC apical area as well as some differences in TJ protein mRNA abundance versus control fish. Data suggest that 18βGA, at low levels, may be adaptogenic in trout and might help to ameliorate ionoregulatory perturbation following IPW exposure. This seems to occur, in part, through 18βGA-induced alterations in the biochemistry and physiology of the gill. PMID:27220746

  14. Waste minimization opportunity assessment: A photofinishing facility. Final report

    SciTech Connect

    Not Available

    1991-08-01

    A waste minimization opportunity assessment was performed which identified areas for waste reduction at a photofinishing facility. The study followed procedures in the EPA Waste Minimization Opportunity Assessment Manual. The report identifies potential options to achieve further waste minimization progress. A number of waste producing processes were initially screened, and detailed technical evaluations were performed on wastes associated with process solutions and wash waters. Options identified were as follows: (1) wash water control; (2) silver recovery--metal replacement cartridges; (3) silver recovery--electrowinning (4) electrowinning with MRC tailing; (5) recovery of silver--ion exchange; (6) recovery of fixer; (7) recovery of bleach fix; and (8) recovery of developer. Based on the results of the assessment phase, Options 1-4 and 7 were selected for further evaluation in the feasibility phase. The results of the study indicate the fastest payback would be realized from Options 1 and 7 assuming Accuphoto's willingness to recycle bleach and no production increases.

  15. Bit Error Rate Analysis for MC-CDMA Systems in Nakagami-[InlineEquation not available: see fulltext.] Fading Channels

    NASA Astrophysics Data System (ADS)

    Li, Zexian; Latva-aho, Matti

    2004-12-01

    Multicarrier code division multiple access (MC-CDMA) is a promising technique that combines orthogonal frequency division multiplexing (OFDM) with CDMA. In this paper, based on an alternative expression for the[InlineEquation not available: see fulltext.]-function, characteristic function and Gaussian approximation, we present a new practical technique for determining the bit error rate (BER) of multiuser MC-CDMA systems in frequency-selective Nakagami-[InlineEquation not available: see fulltext.] fading channels. The results are applicable to systems employing coherent demodulation with maximal ratio combining (MRC) or equal gain combining (EGC). The analysis assumes that different subcarriers experience independent fading channels, which are not necessarily identically distributed. The final average BER is expressed in the form of a single finite range integral and an integrand composed of tabulated functions which can be easily computed numerically. The accuracy of the proposed approach is demonstrated with computer simulations.

  16. MIMO Free-Space Optical Communication Employing Subcarrier Intensity Modulation in Atmospheric Turbulence Channels

    NASA Astrophysics Data System (ADS)

    Ghassemlooy, Zabih; Popoola, Wasiu O.; Ahmadi, Vahid; Leitgeb, Erich

    In this paper, we analyse the error performance of transmitter/receiver array free-space optical (FSO) communication system employing binary phase shift keying (BPSK) subcarrier intensity modulation (SIM) in clear but turbulent atmospheric channel. Subcarrier modulation is employed to eliminate the need for adaptive threshold detector. Direct detection is employed at the receiver and each subcarrier is subsequently demodulated coherently. The effect of irradiance fading is mitigated with an array of lasers and photodetectors. The received signals are linearly combined using the optimal maximum ratio combining (MRC), the equal gain combining (EGC) and the selection combining (SelC). The bit error rate (BER) equations are derived considering additive white Gaussian noise and log normal intensity fluctuations. This work is part of the EU COST actions and EU projects.

  17. Comparison between Coherent and Noncoherent Receivers for UWB Communications

    NASA Astrophysics Data System (ADS)

    Durisi, Giuseppe; Benedetto, Sergio

    2005-12-01

    We present a comparison between coherent and noncoherent UWB receivers, under a realistic propagation environment, that takes into account also the effect of path-dependent pulse distortion. As far as coherent receivers are concerned, both maximal ratio combining (MRC) and equal gain combining (EGC) techniques are analyzed, considering a limited number of estimated paths. Furthermore, two classical noncoherent schemes, a differential detector, and a transmitted-reference receiver, together with two iterative solutions, recently proposed in the literature, are considered. Finally, we extend the multisymbol approach to the UWB case and we propose a decision-feedback receiver that reduces the complexity of the previous strategy, thus still maintaining good performance. While traditional noncoherent receivers exhibit performance loss, if compared to coherent detectors, the iterative and the decision-feedback ones are able to guarantee error probability close to the one obtained employing an ideal RAKE, without requiring channel estimation, in the presence of static indoor channel and limited multiuser interference.

  18. Quantitative analysis of biodiesel in blends of biodiesel and conventional diesel by comprehensive two-dimensional gas chromatography and multivariate curve resolution.

    PubMed

    Mogollon, Noroska Gabriela Salazar; Ribeiro, Fabiana Alves de Lima; Lopez, Monica Mamian; Hantao, Leandro Wang; Poppi, Ronei Jesus; Augusto, Fabio

    2013-09-24

    In this paper, a method to determine the composition of blends of biodiesel with mineral diesel (BXX) by multivariate curve resolution with Alternating Least Squares (MRC-ALS) combined to comprehensive two-dimensional gas chromatography with Flame Ionization Detection (GC×GC-FID) is presented. Chromatographic profiles of BXX blends produced with biodiesels from different sources were used as input data. An initial evaluation carried out after multiway principal component analysis (MPCA) was used to reveal regions of the chromatograms were the signal was likely to be dependent on the concentration of biodiesel, regardless its vegetable source. After this preliminary step MCR-ALS modeling was carried out only using relevant parts of the chromatograms. The resulting procedure was able to predict accurately the concentration of biodiesel in the BXX samples regardless of its origin.

  19. Investigating health information needs of community radio stations and applying the World Wide Web to disseminate audio products.

    PubMed

    Snyders, Janus; van Wyk, Elmarie; van Zyl, Hendra

    2010-01-01

    The Web and Media Technologies Platform (WMTP) of the South African Medical Research Council (MRC) conducted a pilot project amongst community radio stations in South Africa. Based on previous research done in Africa WMTP investigated the following research question: How reliable is the content of health information broadcast by community radio stations? The main objectives of the project were to determine the 1) intervals of health slots on community radio stations, 2) sources used by community radio stations for health slots, 3) type of audio products needed for health slots, and 4) to develop a user friendly Web site in response to the stations' needs for easy access to audio material on health information.

  20. Cytotoxic Guanidine Alkaloids from a French Polynesian Monanchora n. sp. Sponge.

    PubMed

    El-Demerdash, Amr; Moriou, Céline; Martin, Marie-Thérèse; Rodrigues-Stien, Alice de Souza; Petek, Sylvain; Demoy-Schneider, Marina; Hall, Kathryn; Hooper, John N A; Debitus, Cécile; Al-Mourabit, Ali

    2016-08-26

    Four bicyclic and three pentacyclic guanidine alkaloids (1-7) were isolated from a French Polynesian Monanchora n. sp. sponge, along with the known alkaloids monalidine A (8), enantiomers 9-11 of known natural product crambescins, and the known crambescidins 12-15. Structures were assigned by spectroscopic data interpretation. The relative and absolute configurations of the alkaloids were established by analysis of (1)H NMR and NOESY spectra and by circular dichroism analysis. The new norcrambescidic acid (7) corresponds to interesting biosynthetic variation within the pentacyclic core. All compounds exhibited antiproliferative and cytotoxic efficacy against KB, HCT116, HL60, MRC5, and B16F10 cancer cells, with IC50 values ranging from 4 nM to 10 μM. PMID:27419263

  1. Flexible polymeric ultrathin film for mesenchymal stem cell differentiation.

    PubMed

    Pensabene, Virginia; Taccola, Silvia; Ricotti, Leonardo; Ciofani, Gianni; Menciassi, Arianna; Perut, Francesca; Salerno, Manuela; Dario, Paolo; Baldini, Nicola

    2011-07-01

    Ultrathin films (also called nanofilms) are two-dimensional (2-D) polymeric structures with potential application in biology, biotechnology, cosmetics and tissue engineering. Since they can be handled in liquid form with micropipettes or tweezers they have been proposed as flexible systems for cell adhesion and proliferation. In particular, with the aim of designing a novel patch for bone or tendon repair and healing, in this work the biocompatibility, adhesion and proliferation activity of Saos-2, MRC-5 and human and rat mesenchymal stem cells on poly(lactic acid) nanofilms were evaluated. The nanofilms did not impair the growth and differentiation of osteoblasts and chondrocytes. Moreover, nanofilm adhesion to rabbit joints was evident under ex vivo conditions. PMID:21421086

  2. Receiver diversity combining using evolutionary algorithms in Rayleigh fading channel.

    PubMed

    Akbari, Mohsen; Manesh, Mohsen Riahi; El-Saleh, Ayman A; Reza, Ahmed Wasif

    2014-01-01

    In diversity combining at the receiver, the output signal-to-noise ratio (SNR) is often maximized by using the maximal ratio combining (MRC) provided that the channel is perfectly estimated at the receiver. However, channel estimation is rarely perfect in practice, which results in deteriorating the system performance. In this paper, an imperialistic competitive algorithm (ICA) is proposed and compared with two other evolutionary based algorithms, namely, particle swarm optimization (PSO) and genetic algorithm (GA), for diversity combining of signals travelling across the imperfect channels. The proposed algorithm adjusts the combiner weights of the received signal components in such a way that maximizes the SNR and minimizes the bit error rate (BER). The results indicate that the proposed method eliminates the need of channel estimation and can outperform the conventional diversity combining methods.

  3. Receiver Diversity Combining Using Evolutionary Algorithms in Rayleigh Fading Channel

    PubMed Central

    Akbari, Mohsen; Manesh, Mohsen Riahi

    2014-01-01

    In diversity combining at the receiver, the output signal-to-noise ratio (SNR) is often maximized by using the maximal ratio combining (MRC) provided that the channel is perfectly estimated at the receiver. However, channel estimation is rarely perfect in practice, which results in deteriorating the system performance. In this paper, an imperialistic competitive algorithm (ICA) is proposed and compared with two other evolutionary based algorithms, namely, particle swarm optimization (PSO) and genetic algorithm (GA), for diversity combining of signals travelling across the imperfect channels. The proposed algorithm adjusts the combiner weights of the received signal components in such a way that maximizes the SNR and minimizes the bit error rate (BER). The results indicate that the proposed method eliminates the need of channel estimation and can outperform the conventional diversity combining methods. PMID:25045725

  4. Anticancer photodynamic therapy based on the use of a microsystem

    NASA Astrophysics Data System (ADS)

    Jastrzebska, E.; Bulka, N.; Zukowski, K.; Chudy, M.; Brzozka, Z.; Dybko, A.

    2015-07-01

    The paper presents the evaluation of photodynamic therapy (PDT) procedures with an application of a microsystem. Two cell lines were used in the experiments, i.e. human lung carcinoma - A549 and normal human fetal lung fibroblast MRC5. Mono-, coculture and mixed cultures were performed in a microsystem at the same time. The microsystem consisted of a concentration gradient generator (CGG) which generates different concentrations of a photosensitizer, and a set of microchambers for cells. The microchambers were linked by microchannels of various length in order to allow cells migration and in this way cocultures were created. Transparent materials were used for the chip manufacture, i.e. glass and poly(dimethylsiloxane). A high power LED was used to test photodynamic therapy effectiveness in the microsystem.

  5. Light-Weight Radioisotope Heater Unit final safety analysis report (LWRHU-FSAR): Volume 1: A. Introduction and executive summary: B. Reference Design Document (RDD)

    SciTech Connect

    Johnson, E.W.

    1988-10-01

    The orbiter and probe portions of the National Aeronautics and Space Administration (NASA) Galileo spacecraft contain components which require auxiliary heat during the mission. To meet these needs, the Department of Energy's (DOE's) Office of Special Applications (OSA) has sponsored the design, fabrication, and testing of a one-watt encapsulated plutonium dioxide-fueled thermal heater named the Light-Weight Radioisotope Heater Unit (LWRHU). This report, prepared by Monsanto Research Corporation (MRC), addresses the radiological risks which might be encountered by people both at the launch area and worldwide should postulated mission failures or malfunctions occur, resulting in the release of the LWRHUs to the environment. Included are data from the design, mission descriptions, postulated accidents with their consequences, test data, and the derived source terms and personnel exposures for the various events. 11 refs., 44 figs., 11 tabs.

  6. In vitro evaluation of the cytotoxicity of ProRoot MTA and MTA Angelus.

    PubMed

    Koulaouzidou, Elisabeth A; Economides, Nikolaos; Beltes, Panagiotis; Geromichalos, George; Papazisis, Konstantinos

    2008-12-01

    The purpose of the present in vitro study was to compare the cytotoxic effect of two commercially available brands of mineral trioxide cement (ProRoot MTA and MTA Angelus), modified zinc oxide-eugenol cement (SuperEBA) and resin-modified glass ionomer cement (Vitrebond) using rat pulp cells (RPC-C2A) and human lung fibroblasts (MRC-5). The cells were cultured in typical culture conditions and exposed to the tested materials by adaptation of insert wells. The cytotoxic effect was recorded at two observation periods (24 and 72 h) by using a colorimetric assay of tetrazolium reduction (XTT method) in reference to controls. Overall, the degree of cytotoxic effect in ascending order was ProRoot MTA - MTA Angelus < SuperEBA < Vitrebond. Both MTA materials tested exerted mild suppression of cellular mitochondrial activity and may be characterized as biologically inert materials.

  7. Morphogens, modeling and patterning the neural tube: an interview with James Briscoe.

    PubMed

    Briscoe, James

    2015-01-20

    James Briscoe has a BSc in Microbiology and Virology (from the University of Warwick, UK) and a PhD in Molecular and Cellular Biology (from the Imperial Cancer Research Fund, London, now Cancer Research UK). He started working on the development of the neural tube in the lab of Tom Jessel as a postdoctoral fellow, establishing that there was graded sonic hedgehog signaling in the ventral neural tube. He is currently a group leader and Head of Division in Developmental Biology at the MRC National Institute for Medical Research (which will become part of the Francis Crick Institute in April 2015). He is working to understand the molecular and cellular mechanisms of graded signaling in the vertebrate neural tube.We interviewed him about the development of ideas on morphogenetic gradients and his own work on modeling the development of the neural tube for our series on modeling in biology.

  8. Replication of bovine herpesvirus type 4 in human cells in vitro.

    PubMed

    Egyed, L

    1998-07-01

    A reference strain (Movár 33/63) of bovine herpesvirus type 4 (BHV-4) was inoculated into 14 different human cell lines and five primary cell cultures representing various human tissues. BHV-4 replicated in two embryonic lung cell lines, MRC-5 and Wistar-38, and in a giant-cell glioblastoma cell culture. Cytopathic effect and intranuclear inclusion bodies were observed in these cells. PCR detected a 10,000-times-higher level of BHV-4 DNA. Titration of the supernatant indicated a 100-fold increase of infectious particles. Since this is the first bovine (human herpesvirus 8 and Epstein-Barr virus related) herpesvirus which replicates on human cells in vitro, the danger of possible human BHV-4 infection should not be ignored.

  9. Synthesis and antileishmanial activity of new imidazolidin-2-one derivatives.

    PubMed

    Robert, Jean Michel H; Sabourin, Caroline; Alvarez, Nidia; Robert-Piessard, Sylvie; Le Baut, Guillaume; Le Pape, Patrice

    2003-01-01

    N(3)-acyl, arylsulfonyl and benzyl derivatives of N(1)-(4,6-dimethylpyridin-2-yl), (5-methylthiazol-2-yl) or (3-methylisoxazol-5-yl)imidazolidin-2-ones were synthesized and evaluated as potential antileishmanial agents. Determination of their cytotoxic effect was carried out using MRC5 cells. Two compounds, 1-(4,6-dimethylpyridin-2-yl)-3-(napht-2-ylsulfonyl)imidazolidin-2-one, 18, and 1-(3-methylisoxazol-5-yl)-3-(4-bromobenzyl)imidazo-lidin-2-one, 25, exerted significant antileishmanial activity in promastigotes of Leishmania (L) mexicana and Leishmania infantum, with IC(50) in the range of 8-16 micro mol L(-1). Antiparasitical activity of the less toxic compound, 25, was confirmed against intracellular amastigote of L. mexicana, the clinical relevant stage; its low IC(50) value (2.4 micro mol L(-1)) and its favourable toxicity/activity index (11) constitute encouraging results for ongoing pharmacomodulation in the corresponding subseries. PMID:12932902

  10. Sites in human nuclei where damage induced by ultraviolet light is repaired: localization relative to transcription sites and concentrations of proliferating cell nuclear antigen and the tumour suppressor protein, p53.

    PubMed

    Jackson, D A; Hassan, A B; Errington, R J; Cook, P R

    1994-07-01

    The repair of damage induced in DNA by ultraviolet light involves excision of the damaged sequence and synthesis of new DNA to repair the gap. Sites of such repair synthesis were visualized by incubating permeabilized HeLa or MRC-5 cells with the DNA precursor, biotin-dUTP, in a physiological buffer; then incorporated biotin was immunolabeled with fluorescent antibodies. Repair did not take place at sites that reflected the DNA distribution; rather, sites were focally concentrated in a complex pattern. This pattern changed with time; initially intense repair took place at transcriptionally active sites but when transcription became inhibited it continued at sites with little transcription. Repair synthesis in vitro also occurred in the absence of transcription. Repair sites generally contained a high concentration of proliferating cell nuclear antigen but not the tumour-suppressor protein, p53.

  11. Discovery of Potent, Orally Bioavailable Inhibitors of Human Cytomegalovirus.

    PubMed

    Fader, Lee; Brault, Martine; Desjardins, Jessica; Dansereau, Nathalie; Lamorte, Louie; Tremblay, Sonia; Bilodeau, François; Bordeleau, Josée; Duplessis, Martin; Gorys, Vida; Gillard, James; Gleason, James L; James, Clint; Joly, Marc-André; Kuhn, Cyrille; Llinas-Brunet, Montse; Luo, Laibin; Morency, Louis; Morin, Sébastien; Parisien, Mathieu; Poirier, Maude; Thibeault, Carl; Trinh, Thao; Sturino, Claudio; Srivastava, Sanjay; Yoakim, Christiane; Franti, Michael

    2016-05-12

    A high-throughput screen based on a viral replication assay was used to identify inhibitors of the human cytomegalovirus. Using this approach, hit compound 1 was identified as a 4 μM inhibitor of HCMV that was specific and selective over other herpes viruses. Time of addition studies indicated compound 1 exerted its antiviral effect early in the viral life cycle. Mechanism of action studies also revealed that this series inhibited infection of MRC-5 and ARPE19 cells by free virus and via direct cell-to-cell spread from infected to uninfected cells. Preliminary structure-activity relationships demonstrated that the potency of compound 1 could be improved to a low nanomolar level, but metabolic stability was a key optimization parameter for this series. A strategy focused on minimizing metabolic hydrolysis of the N1-amide led to an alternative scaffold in this series with improved metabolic stability and good pharmacokinetic parameters in rat. PMID:27190604

  12. Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas

    PubMed Central

    Wu, Kui; Zhang, Xin; Li, Fuqiang; Xiao, Dakai; Hou, Yong; Zhu, Shida; Liu, Dongbing; Ye, Xiaofei; Ye, Mingzhi; Yang, Jie; Shao, Libin; Pan, Hui; Lu, Na; Yu, Yuan; Liu, Liping; Li, Jin; Huang, Liyan; Tang, Hailing; Deng, Qiuhua; Zheng, Yue; Peng, Lihua; Liu, Geng; Gu, Xia; He, Ping; Gu, Yingying; Lin, Weixuan; He, Huiming; Xie, Guoyun; Liang, Han; An, Na; Wang, Hui; Teixeira, Manuel; Vieira, Joana; Liang, Wenhua; Zhao, Xin; Peng, Zhiyu; Mu, Feng; Zhang, Xiuqing; Xu, Xun; Yang, Huanming; Kristiansen, Karsten; Wang, Jian; Zhong, Nanshan; Wang, Jun; Pan-Hammarström, Qiang; He, Jianxing

    2015-01-01

    The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13 significantly mutated genes are identified, including the most commonly mutated gene TP53 and novel mutation targets such as RHPN2, GLI3 and MRC2. TP53 mutations are furthermore significantly enriched in tumours from patients harbouring metastases. Genes regulating cytoskeleton remodelling processes are also frequently altered, especially in metastatic samples, of which the high expression level of IQGAP3 is identified as a marker for poor prognosis. Our study represents the first large-scale sequencing effort on lung adenocarcinoma in Asian patients and provides a comprehensive mutational landscape for both primary and metastatic tumours. This may thus form a basis for personalized medical care and shed light on the molecular pathogenesis of metastatic lung adenocarcinoma. PMID:26647728

  13. Relation of environmental exposure to erionite fibres to risk of respiratory cancer.

    PubMed

    Simonato, L; Baris, R; Saracci, R; Skidmore, J; Winkelmann, R

    1989-01-01

    During the period 1979-1983, IARC, in collaboration with the Department of Chest Diseases of Hacettepe University in Ankara and the MRC Pneumoconiosis Unit in Penarth, conducted an epidemiological and environmental survey in 4 villages in central Turkey affected by a high incidence of mesothelial tumours. Recent data point to erionite, a zeolite fibre, as the most plausible etiological agent. From animal experiments, erionite appears to be the most powerful carcinogenic fibre so far known. During the study period, 17 pleural mesotheliomas and 7 lung cancer cases have been reported among the villagers. These cancer cases are analysed in relation to exposure to fibres. We assume exposure to occur from birth onwards and therefore consider duration of exposure equal to age. On this basis, the incidence of mesothelial and lung tumours is analysed in relation to age and cumulative exposure to fibres computed using the airborne fibre levels measured during the survey.

  14. Antiproliferative Activity of seco-Oxacassanes from Acacia schaffneri.

    PubMed

    Torres-Valencia, J Martín; Motilva, Virginia; Manríquez-Torres, J Jesús; García-Mauriño, Sofía; López-Lázaro, Miguel; Zbakh, Hanaa; Calderón-Montaño, José M; Gómez-Hurtado, Mario A; Gayosso-De-Lucio, Juan A; Cerda-García-Rojas, Carlos M; Joseph-Nathan, Pedro

    2015-06-01

    This work reports the antiproliferative activity of seco-oxacassanes 1-3, isolated from Acacia schaffneri, against human colon (HT-29), lung (A-549), and melanoma (UACC-62) cancer cell lines, as well as against their non-malignant counterparts CCD-841 CoN, MRC-5, and VH-10, respectively, using the sulforhodamine B test. While compounds 1 and 3 were inactive, 2 presented strong activity with IC50 values between 0.12 and 0.92 μg mL(-1). The cytotoxicity mechanisms of 2 were investigated by cell cycle analysis and through DNA repair pathways, indicating that the compound is capable of arresting the cell cycle in the G0/G1 phase. This effect might be generated through damage to DNA by alkylation. In addition, compound 2 was able to decrease HT-29 migration.

  15. Cell scientist to watch--Melina Schuh.

    PubMed

    Schuh, Melina; Bobrowska, Anna

    2016-01-01

    Melina Schuh received her diploma degree in biochemistry from the University of Bayreuth, Germany, where she completed her Diploma thesis with Stefan Heidmann and Christian Lehner. She went on to do her PhD with Jan Ellenberg at the European Molecular Biology Laboratory in Heidelberg, Germany. In 2009, after a bridging postdoc with Jan, Melina started her own group at the MRC Laboratory of Molecular Biology in Cambridge, UK. Since January 2016, she is a Director at the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany, and will establish a new department focussing on meiosis. She is an EMBO Young Investigator and a recipient of the 2014 Lister Institute Research Prize, the 2014 Biochemical Society Early Career Award and the 2015 John Kendrew Young Scientist Award. Her lab is studying meiosis in mammalian oocytes, including human oocytes.

  16. Biologically active vallesamine, strychnan, and rhazinilam alkaloids from Alstonia: Pneumatophorine, a nor-secovallesamine with unusual incorporation of a 3-ethylpyridine moiety.

    PubMed

    Lim, Jun-Lee; Sim, Kae-Shin; Yong, Kien-Thai; Loong, Bi-Juin; Ting, Kang-Nee; Lim, Siew-Huah; Low, Yun-Yee; Kam, Toh-Seok

    2015-09-01

    Four alkaloids comprising two vallesamine, one strychnan, and one pyranopyridine alkaloid, in addition to 32 other known alkaloids were isolated from two Malayan Alstonia species, Alstonia pneumatophora and Alstonia rostrata. The structures of these alkaloids were determined using NMR and MS analyses, and in one instance, confirmed by X-ray diffraction analysis. The nor-6,7-secovallesamine alkaloid, pneumatophorine, is notable for an unusual incorporation of a 3-ethylpyridine moiety in a monoterpenoid indole. The rhazinilam-type alkaloids (rhazinicine, nor-rhazinicine, rhazinal, and rhazinilam) showed strong cytotoxicity toward human KB, HCT-116, MDA-MB-231, and MRC-5 cells, while pneumatophorine, the uleine alkaloid undulifoline, and the strychnan alkaloids, N4-demethylalstogustine and echitamidine, induced concentration dependent relaxation in phenylephrine-precontracted rat aortic rings.

  17. Intramolecular Radical Aziridination of Allylic Sulfamoyl Azides by Cobalt(II)-Based Metalloradical Catalysis: Effective Construction of Strained Heterobicyclic Structures.

    PubMed

    Jiang, Huiling; Lang, Kai; Lu, Hongjian; Wojtas, Lukasz; Zhang, X Peter

    2016-09-12

    Cobalt(II)-based metalloradical catalysis (MRC) has been successfully applied for effective construction of the highly strained 2-sulfonyl-1,3-diazabicyclo[3.1.0]hexane structures in high yields through intramolecular radical aziridination of allylic sulfamoyl azides. The resulting [3.1.0] bicyclic aziridines prove to be versatile synthons for the preparation of a diverse range of 1,2- and 1,3-diamine derivatives by selective ring-opening reactions. As a demonstration of its application for target synthesis, the metalloradical intramolecular aziridination reaction has been incorporated as a key step for efficient synthesis of a potent neurokinin 1 (NK1 ) antagonist in 60 % overall yield. PMID:27511474

  18. The 2009 Nobel Prize in Chemistry: Thomas A. Steitz and the Structure of the Ribosome

    PubMed Central

    Zhao, Peter

    2011-01-01

    Over the past 200 years, there have been countless groundbreaking discoveries in biology and medicine at Yale University. However, one particularly noteworthy discovery with profoundly important and broad consequences happened here in just the past two decades. In 2009, Thomas Steitz, the Sterling Professor of Molecular Biophysics & Biochemistry, was awarded the Nobel Prize in Chemistry for “studies of the structure and function of the ribosome,” along with Venkatraman Ramakrishnan of the MRC Laboratory of Molecular Biology and Ada E. Yonath of the Weizmann Institute of Science. This article covers the historical context of Steitz’s important discovery, the techniques his laboratory used to study the ribosome, and the impact that this research has had, and will have, on the future of biological and medical research. PMID:21698044

  19. The 2009 Nobel Prize in Chemistry: Thomas A. Steitz and the structure of the ribosome.

    PubMed

    Zhao, Peter

    2011-06-01

    Over the past 200 years, there have been countless groundbreaking discoveries in biology and medicine at Yale University. However, one particularly noteworthy discovery with profoundly important and broad consequences happened here in just the past two decades. In 2009, Thomas Steitz, the Sterling Professor of Molecular Biophysics & Biochemistry, was awarded the Nobel Prize in Chemistry for "studies of the structure and function of the ribosome," along with Venkatraman Ramakrishnan of the MRC Laboratory of Molecular Biology and Ada E. Yonath of the Weizmann Institute of Science. This article covers the historical context of Steitz's important discovery, the techniques his laboratory used to study the ribosome, and the impact that this research has had, and will have, on the future of biological and medical research.

  20. Human 2-D PAGE databases for proteome analysis in health and disease: http://biobase.dk/cgi-bin/celis.

    PubMed

    Celis, J E; Gromov, P; Ostergaard, M; Madsen, P; Honoré, B; Dejgaard, K; Olsen, E; Vorum, H; Kristensen, D B; Gromova, I; Haunsø, A; Van Damme, J; Puype, M; Vandekerckhove, J; Rasmussen, H H

    1996-12-01

    Human 2-D PAGE Databases established at the Danish Centre for Human Genome Research are now available on the World Wide Web (http://biobase.dk/cgi-bin/celis). The databanks, which offer a comprehensive approach to the analysis of the human proteome both in health and disease, contain data on known and unknown proteins recorded in various IEF and NEPHGE 2-D PAGE reference maps (non-cultured keratinocytes, non-cultured transitional cell carcinomas, MRC-5 fibroblasts and urine). One can display names and information on specific protein spots by clicking on the image of the gel representing the 2-D gel map in which one is interested. In addition, the database can be searched by protein name, keywords or organelle or cellular component. The entry files contain links to other databases such as Medline, Swiss-Prot, PIR, PDB, CySPID, OMIM, Methabolic pathways, etc. The on-line information is updated regularly. PMID:8977092

  1. Preparation and toxicological evaluation of methyl pyranoanthocyanin.

    PubMed

    Zhu, Zhenzhou; Wu, Nao; Kuang, Minjie; Lamikanra, Olusola; Liu, Gang; Li, Shuyi; He, Jingren

    2015-09-01

    Anthocyanins are increasingly valued in the food industry for their functional properties and as food colorants. The broadness of their applications has, however, been limited by the lack of stability of these natural pigment extracts in a number of food systems. The potential application of pyranoanthocyanins, anthocyanin derivatives with better stability conferred by the added pyran ring, as a food ingredient was determined. Methylpyranoanthocyanin (MPA) was prepared from reaction of acetone and anthocyanin extracts from red grapes. Reaction products were sequentially purified with polyamide resin, TSK gel resin and semi-preparative HPLC to a purity level >98%. Cytoprotective influence tests of the purified MPA indicated its significant protective effect against H2O2 induced MRC-5 cell damage. Results of evaluations of possible acute toxicity effects on MPA-fed mice, including macro and microscopic assessments, support the conclusion of a non-toxic effect of MPA, and its potential safe use as a food additive.

  2. Mangromicins A and B: structure and antitrypanosomal activity of two new cyclopentadecane compounds from Lechevalieria aerocolonigenes K10-0216.

    PubMed

    Nakashima, Takuji; Iwatsuki, Masato; Ochiai, Junya; Kamiya, Yoshiyuki; Nagai, Kenichiro; Matsumoto, Atsuko; Ishiyama, Aki; Otoguro, Kazuhiko; Shiomi, Kazuro; Takahashi, Yōko; Ōmura, Satoshi

    2014-03-01

    Two new cyclopentadecane antibiotics, named mangromicins A and B, were separated out from the culture broth of Lechevalieria aerocolonigenes K10-0216 by Diaion HP-20, silica gel and ODS column chromatography, and were finally purified by HPLC. The chemical structures of the two novel compounds were elucidated by instrumental analyses, including various NMR, MS and X-ray crystallography. Mangromicins A and B consist of cyclopentadecane skeletons with a tetrahydrofuran unit and a 5,6-dihydro-4-hydroxy-2-pyrone moiety. Mangromicins A and B showed in vitro antitrypanosomal activity with IC50 values of 2.4 and 43.4 μg ml(-1), respectively. The IC50 values of both compounds were lower than those of cytotoxicity against MRC-5 human fetal lung fibroblast cells.

  3. [Radiation Tolerant Electronics

    NASA Technical Reports Server (NTRS)

    1996-01-01

    Research work in the providing radiation tolerant electronics to NASA and the commercial sector is reported herein. There are four major sections to this report: (1) Special purpose VLSI technology section discusses the status of the VLSI projects as well as the new background technologies that have been developed; (2) Lossless data compression results provide the background and direction of new data compression pursued under this grant; (3) Commercial technology transfer presents an itemization of the commercial technology transfer; and (4) Delivery of VLSI to the Government is a solution and progress report that shows how the Government and Government contractors are gaining access to the technology that has been developed by the MRC.

  4. Antimicrobial Assessment of Resins from Calophyllum Antillanum and Calophyllum Inophyllum.

    PubMed

    Cuesta-Rubio, Osmany; Oubada, Ahmad; Bello, Adonis; Maes, Louis; Cos, Paul; Monzote, Lianet

    2015-12-01

    The Calophyllum genus is well-known for its antimicrobial and cytotoxic activities, and therefore, we analyzed these biological activities for resins of Calophyllum antillanum and Calophyllum inophyllum growing in Cuba. C. antillanum resins showed a potent activity against Plasmodium falciparum (IC50  = 0.3 ± 0.1 µg/mL), while its cytotoxicity against MRC-5 cells was much lower (IC50  = 21.6 ± 1.1 µg/mL). In contrary, the resin of C. inophyllum showed an unspecific activity. The presence of apetalic acid, isoapetalic acid, calolongic acid, pinetoric acid I, pinetoric acid II, isocalolongic acid, pinetoric acid III, and isopinetoric acid III in C. antillanum resins was also confirmed. These results demonstrated for the first time the potential activity of C. antillanum resins against P. falciparum.

  5. Is there an optimum detector size for digital night vision goggles?

    NASA Astrophysics Data System (ADS)

    Holst, Gerald C.

    2016-05-01

    In previous studies maximum acquisition range was achieved when Fλ/d approached 2. There was no constraint on magnification or field-of-view. This suggested that detector size approach λ/2 when F = 1. Night vision goggles typically have a fixed FOV of 40 deg with unity magnification. Digital night vision goggles (DNVG) acquisition range is limited by the human visual system resolution of 0.291 mrad (20/20 vision). This suggests the maximum number of horizontal detectors should be about 2500 with a minimum pixel size of about 8 μm when F = 1 and aperture = 1 inch. Values change somewhat depending upon f-number and noise level. Ranges are provided for GaAs and InGaAs detectors under starlight conditions. The different spectral responses create minimum resolvable contrast (MRC) test issues.

  6. Exploring Synthetic and Systems Biology at the University of Edinburgh.

    PubMed

    Fletcher, Liz; Rosser, Susan; Elfick, Alistair

    2016-06-15

    The Centre for Synthetic and Systems Biology ('SynthSys') was originally established in 2007 as the Centre for Integrative Systems Biology, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Engineering and Physical Sciences Research Council (EPSRC). Today, SynthSys embraces an extensive multidisciplinary community of more than 200 researchers from across the University with a common interest in synthetic and systems biology. Our research is broad and deep, addressing a diversity of scientific questions, with wide ranging impact. We bring together the power of synthetic biology and systems approaches to focus on three core thematic areas: industrial biotechnology, agriculture and the environment, and medicine and healthcare. In October 2015, we opened a newly refurbished building as a physical hub for our new U.K. Centre for Mammalian Synthetic Biology funded by the BBSRC/EPSRC/MRC as part of the U.K. Research Councils' Synthetic Biology for Growth programme.

  7. Synthesis, structure and antifungal activity of thiophene-2,3-dicarboxaldehyde bis(thiosemicarbazone) and nickel(II), copper(II) and cadmium(II) complexes: unsymmetrical coordination mode of nickel complex.

    PubMed

    Alomar, Kusaï; Landreau, Anne; Allain, Magali; Bouet, Gilles; Larcher, Gérald

    2013-09-01

    The reaction of nickel(II), copper(II) chlorides and cadmium(II) chloride and bromide with thiophene-2,3-dicarboxaldehyde bis(thiosemicarbazone) (2,3BTSTCH2) leads to a series of new complexes: [Ni(2,3BTSTCH)]Cl, [Cu(2,3BTSTC)], [CdCl2(2,3BTSTCH2)] and [CdBr2(2,3BTSTCH2)]. The crystal structures of the ligand and of [Ni(2,3BTSTCH)]Cl complex have been determined. In this case, we remark an unusual non-symmetrical coordination mode for the two functional groups: one acting as a thione and the second as a deprotonated thiolate. All compounds have been tested for their antifungal activity against human pathogenic fungi: Candida albicans, Candida glabrata and Aspergillus fumigatus, the cadmium complexes exhibit the highest antifungal activity. Cytotoxicity was evaluated using two biological methods: human MRC5 cultured cells and brine shrimp Artemia salina bioassay.

  8. Cell scientist to watch - Emmanuel Boucrot.

    PubMed

    2016-09-01

    Emmanuel Boucrot obtained an undergraduate and a master's degree in biochemistry at the University of Geneva in Switzerland. He pursued his PhD in immunology at the University of Aix-Marseille II in France, supervised by Stéphane Méresse in the laboratory of Jean-Pierre Gorvel. Emmanuel moved to the USA for his postdoctoral training in the laboratory of Tomas Kirchhausen at Harvard Medical School, first as an EMBO fellow and then as a Human Frontiers Science Program fellow. Before starting his own laboratory in 2011, Emmanuel held another postdoctoral position in the laboratory of Harvey McMahon at the MRC Laboratory of Molecular Biology in Cambridge, UK. He is a recipient of a Lister Institute Research Prize and a BBSRC David Phillips Research Fellowship. His group at University College London is interested in studying the mechanisms of clathrin-independent endocytosis, as well as investigating properties of quiescent cells.

  9. Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas.

    PubMed

    Wu, Kui; Zhang, Xin; Li, Fuqiang; Xiao, Dakai; Hou, Yong; Zhu, Shida; Liu, Dongbing; Ye, Xiaofei; Ye, Mingzhi; Yang, Jie; Shao, Libin; Pan, Hui; Lu, Na; Yu, Yuan; Liu, Liping; Li, Jin; Huang, Liyan; Tang, Hailing; Deng, Qiuhua; Zheng, Yue; Peng, Lihua; Liu, Geng; Gu, Xia; He, Ping; Gu, Yingying; Lin, Weixuan; He, Huiming; Xie, Guoyun; Liang, Han; An, Na; Wang, Hui; Teixeira, Manuel; Vieira, Joana; Liang, Wenhua; Zhao, Xin; Peng, Zhiyu; Mu, Feng; Zhang, Xiuqing; Xu, Xun; Yang, Huanming; Kristiansen, Karsten; Wang, Jian; Zhong, Nanshan; Wang, Jun; Pan-Hammarström, Qiang; He, Jianxing

    2015-01-01

    The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13 significantly mutated genes are identified, including the most commonly mutated gene TP53 and novel mutation targets such as RHPN2, GLI3 and MRC2. TP53 mutations are furthermore significantly enriched in tumours from patients harbouring metastases. Genes regulating cytoskeleton remodelling processes are also frequently altered, especially in metastatic samples, of which the high expression level of IQGAP3 is identified as a marker for poor prognosis. Our study represents the first large-scale sequencing effort on lung adenocarcinoma in Asian patients and provides a comprehensive mutational landscape for both primary and metastatic tumours. This may thus form a basis for personalized medical care and shed light on the molecular pathogenesis of metastatic lung adenocarcinoma. PMID:26647728

  10. Cdc14B depletion leads to centriole amplification and its overexpression prevents unscheduled centriole duplication

    SciTech Connect

    Wu, Jun; Plumley, Hyekyung; Rhee, David; Johnson, Dabney K; Dunlap, John; Liu, Yie; Wang, Yisong

    2008-01-01

    Centrosome duplication is tightly controlled in coordination with DNA replication. The molecular mechanism of centrosome duplication remains unclear. Previous studies found that a fraction of human proline-directed phosphatase Cdc14B associates with centrosomes. However, Cdc14B's involvement in centrosome cycle control has never been explored. Here, we show that depletion of Cdc14B by RNA interference leads to centriole amplification in both HeLa and normal human fibroblast BJ and MRC-5 cells. Induction of Cdc14B expression through a regulatable promoter significantly attenuates centriole amplification in prolonged S-phase arrested cells and proteasome inhibitor Z-L3VS-treated cells. This inhibitory function requires centriole-associated Cdc14B catalytic activity. Together, these results suggest a potential function for Cdc14B phosphatase in maintaining the fidelity of centrosome duplication cycle.

  11. Supporting grid-based clinical trials in Scotland.

    PubMed

    Sinnott, R O; Stell, A J; Ajayi, O

    2008-06-01

    A computational infrastructure to underpin complex clinical trials and medical population studies is highly desirable. This should allow access to a range of distributed clinical data sets; support the efficient processing and analysis of the data obtained; have security at its heart; and ensure that authorized individuals are able to see privileged data and no more. Each clinical trial has its own requirements on data sets and how they are used; hence a reusable and flexible framework offers many advantages. The MRC funded Virtual Organisations for Trials and Epidemiological Studies (VOTES) is a collaborative project involving several UK universities specifically to explore this space. This article presents the experiences of developing the Scottish component of this nationwide infrastructure, by the National e-Science Centre (NeSC) based at the University of Glasgow, and the issues inherent in accessing and using the clinical data sets in a flexible, dynamic and secure manner. PMID:18477596

  12. Supporting grid-based clinical trials in Scotland.

    PubMed

    Sinnott, R O; Stell, A J; Ajayi, O

    2008-06-01

    A computational infrastructure to underpin complex clinical trials and medical population studies is highly desirable. This should allow access to a range of distributed clinical data sets; support the efficient processing and analysis of the data obtained; have security at its heart; and ensure that authorized individuals are able to see privileged data and no more. Each clinical trial has its own requirements on data sets and how they are used; hence a reusable and flexible framework offers many advantages. The MRC funded Virtual Organisations for Trials and Epidemiological Studies (VOTES) is a collaborative project involving several UK universities specifically to explore this space. This article presents the experiences of developing the Scottish component of this nationwide infrastructure, by the National e-Science Centre (NeSC) based at the University of Glasgow, and the issues inherent in accessing and using the clinical data sets in a flexible, dynamic and secure manner.

  13. Channel Characterization and Robust Tracking for Diversity Reception over Time-Variant Off-Body Wireless Communication Channels

    NASA Astrophysics Data System (ADS)

    Van Torre, Patrick; Vallozzi, Luigi; Rogier, Hendrik; Moeneclaey, Marc; Verhaevert, Jo

    2010-12-01

    In the 2.45 GHz band, indoor wireless off-body data communication by a moving person can be problematic due to time-variant signal fading and the consequent variation in channel parameters. Off-body communication specifically suffers from the combined effects of fading, shadowing, and path loss due to time-variant multipath propagation in combination with shadowing by the human body. Measurements are performed to analyze the autocorrelation, coherence time, and power spectral density for a person equipped with a wearable receive system moving at different speeds for different configurations and antenna positions. Diversity reception with multiple textile antennas integrated in the clothing provides a means of improving the reliability of the link. For the dynamic channel estimation, a scheme using hard decision feedback after MRC with adaptive low-pass filtering is demonstrated to be successful in providing robust data detection for long data bursts, in the presence of dramatic channel variation.

  14. An outbreak of herpes rugbiorum managed by vaccination of players and sociosexual contacts.

    PubMed

    Skinner, G R; Davies, J; Ahmad, A; McLeish, P; Buchan, A

    1996-11-01

    An outbreak of herpes rugbiorum involved nine players including the scrum half and the full back. The infection was characterized by significant constitutional upset with decreased levels of general fitness and match performance for 1-4 months following the outbreak; one player had herpetic lesions on his right eyelid and corneum. Every infected player, 15 non-infected players and five sociosexual contacts received two vaccinations with intracellular subunit vaccine NFU. Ac. HSV-1 (S-MRC5). None of the players or contacts developed cutaneous herpetic recurrence during a follow-up period of 3 years; the player with ocular disease had one recurrence at 30 months following the original episode. These findings encourage consideration of prophylactic or post-exposure vaccination of participants in rugby or other contact sports with this or other appropriate herpes simplex vaccine. PMID:8945704

  15. Educational Attainment and Women’s Environmental Mastery in Midlife

    PubMed Central

    Deeg, Dorly; Kuh, Diana

    2016-01-01

    Using data from 1,184 women in the MRC National Survey of Health and Development, we estimated associations between education and Ryff’s environmental mastery scale scores at age 52. Confirmatory factor analysis indicated two subscales, here termed mastery skills and mastery accomplishments. Low education was associated with higher mastery skills. This was partly explained by childhood socioeconomic position, as mastery was lower among those with fathers in the most and least advantaged occupational classes. Education was not associated with mastery accomplishments in unadjusted models. Lower ambitions for family/home were associated with higher mastery accomplishments and may have partly suppressed as an association between education and mastery accomplishments. This study highlights childhood as well as adult correlates of mastery and adds to mounting evidence that higher mastery is not universally found among those who are more educated. PMID:27048696

  16. The effect of anakinra, an IL1 receptor antagonist, in patients with sporadic inclusion body myositis (sIBM): a small pilot study.

    PubMed

    Kosmidis, Michalis L; Alexopoulos, Harry; Tzioufas, Athanasios G; Dalakas, Marinos C

    2013-11-15

    In sIBM, an inflammatory process mediated by cytotoxic T cells and cytokines in conjunction with a degenerative process, deposits of beta amyloid and misfolded proteins appear to be the main culprits in disease pathogenesis. IL-1β may play a key role because it is upregulated in sIBM myofibers, co-localizes with Amyloid Precursor Protein (APP) and promotes the production of APP and amyloid deposits. We performed a small, pilot study to examine whether anakinra, an IL1 receptor antagonist could benefit sIBM patients. Four patients with biopsy-proven sIBM received anakinra for a mean period of 7.7 months. No improvement in muscle strength or stabilization was noted in any of the patients based on grip strength and MRC measurements. The treatment failure may be due to insufficiency of anakinra to suppress the intramuscular IL1, the short study period, or the irrelevance of IL1 in the disease process.

  17. Frequent alterations in cytoskeleton remodelling genes in primary and metastatic lung adenocarcinomas.

    PubMed

    Wu, Kui; Zhang, Xin; Li, Fuqiang; Xiao, Dakai; Hou, Yong; Zhu, Shida; Liu, Dongbing; Ye, Xiaofei; Ye, Mingzhi; Yang, Jie; Shao, Libin; Pan, Hui; Lu, Na; Yu, Yuan; Liu, Liping; Li, Jin; Huang, Liyan; Tang, Hailing; Deng, Qiuhua; Zheng, Yue; Peng, Lihua; Liu, Geng; Gu, Xia; He, Ping; Gu, Yingying; Lin, Weixuan; He, Huiming; Xie, Guoyun; Liang, Han; An, Na; Wang, Hui; Teixeira, Manuel; Vieira, Joana; Liang, Wenhua; Zhao, Xin; Peng, Zhiyu; Mu, Feng; Zhang, Xiuqing; Xu, Xun; Yang, Huanming; Kristiansen, Karsten; Wang, Jian; Zhong, Nanshan; Wang, Jun; Pan-Hammarström, Qiang; He, Jianxing

    2015-12-09

    The landscape of genetic alterations in lung adenocarcinoma derived from Asian patients is largely uncharacterized. Here we present an integrated genomic and transcriptomic analysis of 335 primary lung adenocarcinomas and 35 corresponding lymph node metastases from Chinese patients. Altogether 13 significantly mutated genes are identified, including the most commonly mutated gene TP53 and novel mutation targets such as RHPN2, GLI3 and MRC2. TP53 mutations are furthermore significantly enriched in tumours from patients harbouring metastases. Genes regulating cytoskeleton remodelling processes are also frequently altered, especially in metastatic samples, of which the high expression level of IQGAP3 is identified as a marker for poor prognosis. Our study represents the first large-scale sequencing effort on lung adenocarcinoma in Asian patients and provides a comprehensive mutational landscape for both primary and metastatic tumours. This may thus form a basis for personalized medical care and shed light on the molecular pathogenesis of metastatic lung adenocarcinoma.

  18. Mcm2-7 Is an Active Player in the DNA Replication Checkpoint Signaling Cascade via Proposed Modulation of Its DNA Gate

    PubMed Central

    Tsai, Feng-Ling; Vijayraghavan, Sriram; Prinz, Joseph; MacAlpine, Heather K.; MacAlpine, David M.

    2015-01-01

    The DNA replication checkpoint (DRC) monitors and responds to stalled replication forks to prevent genomic instability. How core replication factors integrate into this phosphorylation cascade is incompletely understood. Here, through analysis of a unique mcm allele targeting a specific ATPase active site (mcm2DENQ), we show that the Mcm2-7 replicative helicase has a novel DRC function as part of the signal transduction cascade. This allele exhibits normal downstream mediator (Mrc1) phosphorylation, implying DRC sensor kinase activation. However, the mutant also exhibits defective effector kinase (Rad53) activation and classic DRC phenotypes. Our previous in vitro analysis showed that the mcm2DENQ mutation prevents a specific conformational change in the Mcm2-7 hexamer. We infer that this conformational change is required for its DRC role and propose that it allosterically facilitates Rad53 activation to ensure a replication-specific checkpoint response. PMID:25870112

  19. The Human PAX6 Mutation Database.

    PubMed

    Brown, A; McKie, M; van Heyningen, V; Prosser, J

    1998-01-01

    The Human PAX6 Mutation Database contains details of 94 mutations of the PAX6 gene. A Microsoft Access program is used by the Curator to store, update and search the database entries. Mutations can be entered directly by the Curator, or imported from submissions made via the World Wide Web. The PAX6 Mutation Database web page at URL http://www.hgu.mrc.ac.uk/Softdata/PAX6/ provides information about PAX6, as well as a fill-in form through which new mutations can be submitted to the Curator. A search facility allows remote users to query the database. A plain text format file of the data can be downloaded via the World Wide Web. The Curation program contains prior knowledge of the genetic code and of the PAX6 gene including cDNA sequence, location of intron/exon boundaries, and protein domains, so that the minimum of information need be provided by the submitter or Curator.

  20. Final report on evaluation of cyclocraft support of oil and gas operations in wetland areas

    SciTech Connect

    Eggington, W.J.; Stevens, P.M.; John, C.J.; Harder, B.J.; Lindstedt, D.M.

    1994-10-01

    The cyclocraft is a proven hybrid aircraft, capable of VTOL, lifting heavy and bulky loads, highly controllable, having high safety characteristics and low operating costs. Mission Research Corporation (MRC), under Department of Energy sponsorship, is evaluating the potential use of cyclocraft in the transport of drill rigs, mud, pipes and other materials and equipment, in a cost effective and environmentally safe manner, to support oil and gas drilling, production, and transportation operations in wetland areas. Based upon the results of an earlier parametric study, a cyclocraft design, having a payload capacity of 45 tons and designated H.1 Cyclocraft, was selected for further study, including the preparation of a preliminary design and a development plan, and the determination of operating costs. This report contains all of the results derived from the program to evaluate the use of cyclocraft in the support of oil and gas drilling and production operations in wetland areas.

  1. Treatment outcome of CRLF2-rearranged childhood acute lymphoblastic leukaemia: a comparative analysis of the AIEOP-BFM and UK NCRI-CCLG study groups.

    PubMed

    Attarbaschi, Andishe; Morak, Maria; Cario, Gunnar; Cazzaniga, Giovanni; Ensor, Hannah M; te Kronnie, Truus; Bradtke, Jutta; Mann, Georg; Vendramini, Elena; Palmi, Chiara; Schwab, Claire; Russell, Lisa J; Schrappe, Martin; Conter, Valentino; Mitchell, Christopher D; Strehl, Sabine; Zimmermann, Martin; Pötschger, Ulrike; Harrison, Christine J; Stanulla, Martin; Panzer-Grümayer, Renate; Haas, Oskar A; Moorman, Anthony V

    2012-09-01

    The prognostic relevance of CRLF2 -rearrangements in childhood acute B-cell precursor lymphoblastic leukaemia (ALL), was assessed by a comparative analysis of 114 non-Down-syndrome patients (99 P2RY8-CRLF2+ , 15 IGH@-CRLF2+ ), 76 from the AIEOP-BFM ALL 2000 and 38 from the MRC ALL97 trials. The 6-year cumulative relapse incidence of P2RY8-CRLF2+ patients treated on the two trials was not statistically different: 0·37 ± 0·06 vs. 0·25 ± 0·08 (P = 0·194). In contrast, 0/9 IGH@-CRLF2+ AIEOP-BFM, but 5/6 ALL97 patients relapsed. Conclusively, P2RY8-CRLF2+ patients had an intermediate protocol-independent outcome while the different prognosis of IGH@-CRLF2+ patients could be related to the different structures of the applied treatment protocols.

  2. Complete nucleotide sequence of plasmid plca36 isolated from Lactobacillus casei Zhang.

    PubMed

    Zhang, Wenyi; Yu, Dongliang; Sun, Zhihong; Chen, Xia; Bao, Qiuhua; Meng, He; Hu, Songnian; Zhang, Heping

    2008-09-01

    The complete 36,487 bp sequence of plasmid plca36 from Lactobacillus casei Zhang was determined. Plca36 contains 44 predicted coding regions, and to 23 of them functions could be assigned. For the first time, we identified a relBE toxin-antitoxin (TA) locus in a Lactobacillus genus, perhaps indicating a potential role for plca36 in host survival under extreme nutritional stress. A region encoding a cluster of conjugation genes (tra) was also identified. The cluster showed high similarity and co-linearity with tra regions of pWCFS103 and pMRC01 from Lactobacillus plantarum and Lactococcus lactis, respectively. Comparative gene analysis revealed that plasmids from the genus Lactobacillus may have contributed to the environmental adaptation mainly by providing carbohydrate and amino acid transporters. In addition, two chromosome-encoded relBE systems in Lactobacillus johnsonii and Lactobacillus gasseri were identified. PMID:18634821

  3. Antimicrobial prenylated benzoylphloroglucinol derivatives and xanthones from the leaves of Garcinia goudotiana.

    PubMed

    Mahamodo, Sania; Rivière, Céline; Neut, Christel; Abedini, Amin; Ranarivelo, Heritiana; Duhal, Nathalie; Roumy, Vincent; Hennebelle, Thierry; Sahpaz, Sevser; Lemoine, Amélie; Razafimahefa, Dorothée; Razanamahefa, Bakonirina; Bailleul, François; Andriamihaja, Bakolinirina

    2014-06-01

    Bioassay-guided fractionation using antimicrobial assay of the crude acetonic extract of Garcinia goudotiana leaves and of its five partitions led to the isolation of two new prenylated benzoylphloroglucinol derivatives, goudotianone 1 (1) and goudotianone 2 (2), in addition to two known compounds including one xanthone, 1,3,7-trihydroxy-2-isoprenylxanthone (3), and one triterpenoid, friedelin (4). Their structures were elucidated on the basis of different spectroscopic methods, including extensive 1D- and 2D-NMR spectroscopy and mass spectrometry. The crude acetonic extract, the methylene chloride and ethyl acetate partitions, and some tested compounds isolated from this species (1-3) demonstrated selective significant antimicrobial activities against Gram-positive bacteria, in particular Staphylococcus lugdunensis, Enterococcus faecalis and Mycobacterium smegmatis. The potential cytotoxic activities of these extracts and compounds were evaluated against human colon carcinoma HT29 and human fetal lung fibroblast MRC5 cells.

  4. In vitro anti-microbial activity of the Cuban medicinal plants Simarouba glauca DC, Melaleuca leucadendron L and Artemisia absinthium L.

    PubMed

    Valdés, Aymé Fernández-Calienes; Martínez, Judith Mendiola; Lizama, Ramón Scull; Vermeersch, Marieke; Cos, Paul; Maes, Louis

    2008-09-01

    In the present study, an extensive in vitro antimicrobial profiling was performed for three medicinal plants grown in Cuba, namely Simarouba glauca, Melaleuca leucadendron and Artemisia absinthium. Ethanol extracts were tested for their antiprotozoal potential against Trypanosoma b. brucei, Trypanosoma cruzi, Leishmania infantum and Plasmodium falciparum. Antifungal activities were evaluated against Microsporum canis and Candida albicans whereas Escherichia coli and Staphylococcus aureus were used as test organisms for antibacterial activity. Cytotoxicity was assessed against human MRC-5 cells. Only M. leucadendron extract showed selective activity against microorganisms tested. Although S. glauca exhibited strong activity against all protozoa, it must be considered non-specific. The value of integrated evaluation of extracts with particular reference to selectivity is discussed. PMID:18949336

  5. Nonspecific lymphocyte responses in F344 and LEW rats: susceptibility to murine respiratory mycoplasmosis and examination of cellular basis for strain differences.

    PubMed Central

    Davis, J K; Simecka, J W; Williamson, J S; Ross, S E; Juliana, M M; Thorp, R B; Cassell, G H

    1985-01-01

    Mycoplasma pulmonis produces a mitogen which may play a role in the pathogenesis of murine respiratory mycoplasmosis in rats. Since LEW rats are more susceptible to this disease than F344 rats are, these two strains were used to examine a possible association between disease severity and the level of nonspecific lymphocyte stimulation by mitogens, including M. pulmonis membrane preparations. F344 and LEW spleen, lung, blood, and lymph node lymphocytes were exposed to various mitogens. LEW lymphocytes gave a significantly higher response to mitogenic stimulation, regardless of their anatomical source. These differences in lymphocyte responsiveness were primarily due to differences within the nonadherent cell population. Significantly higher numbers of W3/25+ (T helper) cells were found in LEW lymphoid populations, whereas no difference was found in MRC OX-8+ (T suppressor/cytotoxic) cells. These data suggest an association between disease severity and host responsiveness to nonspecific stimuli. PMID:3159678

  6. SCOP: a structural classification of proteins database.

    PubMed

    Hubbard, T J; Murzin, A G; Brenner, S E; Chothia, C

    1997-01-01

    The Structural Classification of Proteins (SCOP) database provides a detailed and comprehensive description of the relationships of all known proteins structures. The classification is on hierarchical levels: the first two levels, family and superfamily, describe near and far evolutionary relationships; the third, fold, describes geometrical relationships. The distinction between evolutionary relationships and those that arise from the physics and chemistry of proteins is a feature that is unique to this database, so far. SCOP also provides for each structure links to atomic co-ordinates, images of the structures, interactive viewers, sequence data, data on any conformational changes related to function and literature references. The database is freely accessible on the World Wide Web (WWW) with an entry point at URL http://scop.mrc-lmb.cam.ac.uk/scop/

  7. High redshift radio galaxies

    NASA Technical Reports Server (NTRS)

    Mccarthy, Patrick J.

    1993-01-01

    High redshift galaxies that host powerful radio sources are examined. An overview is presented of the content of radio surveys: 3CR and 3CRR, 4C and 4C/USS, B2/1 Jy, MG, MRC/1Jy, Parkes/PSR, B3, and ESO Key-Project. Narrow-line radio galaxies in the visible and UV, the source of ionization and excitation of the emission lines, emission-line luminosities, morphology of the line-emitting gas, physical properties and energetics, kinematics of the line-emitting gas, and implications from the emission lines are discussed. The morphologies and environments of the host galaxies, the alignment effect, and spectral energy distributions and ages are also examined.

  8. Cell scientist to watch--Melina Schuh.

    PubMed

    Schuh, Melina; Bobrowska, Anna

    2016-01-01

    Melina Schuh received her diploma degree in biochemistry from the University of Bayreuth, Germany, where she completed her Diploma thesis with Stefan Heidmann and Christian Lehner. She went on to do her PhD with Jan Ellenberg at the European Molecular Biology Laboratory in Heidelberg, Germany. In 2009, after a bridging postdoc with Jan, Melina started her own group at the MRC Laboratory of Molecular Biology in Cambridge, UK. Since January 2016, she is a Director at the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany, and will establish a new department focussing on meiosis. She is an EMBO Young Investigator and a recipient of the 2014 Lister Institute Research Prize, the 2014 Biochemical Society Early Career Award and the 2015 John Kendrew Young Scientist Award. Her lab is studying meiosis in mammalian oocytes, including human oocytes. PMID:26729026

  9. Overview of measles and mumps vaccine: origin, present, and future of vaccine production.

    PubMed

    Betáková, T; Svetlíková, D; Gocník, M

    2013-01-01

    Measles and mumps are common viral childhood diseases that can cause serious complications. Vaccination remains the most efficient way to control the spread of these viruses. The manufacturing capability for viral vaccines produced in embryonated hen eggs and conventional/classical cell substrates, such as chicken embryo fibroblast or primary dog kidney cell substrates, is no longer sufficient. This limitation can be overcome by utilizing other recognized cell substrates such as Madin Darby Canine Kidney (MDCK), Chinese Hamster Ovary (CHO), Vero (monkey origin) cells, MRC-5 (human diploid) or as an alternative, introducing new cell substrates of human or avian origin. A very important factor in vaccine production is the safety and immunogenicity of the final vaccine, where the proper choice of cell substrate used for virus propagation is made. All substrates used in vaccine production must be fully characterized to avoid the contamination of hidden unknown pathogens which is difficult to achieve in primary cell substrates.

  10. An integrated PIN-array receiver for visible light communication

    NASA Astrophysics Data System (ADS)

    Li, Jie-Hui; Huang, Xing-Xing; Ji, Xin-Ming; Chi, Nan; Shi, Jian-Yang

    2015-10-01

    This paper first designs and demonstrates an integrated receiver for a visible light communication (VLC) system based on RGB LED and an array of silicon PIN diode detectors. The system uses a maximal ratio combining (MRC) algorithm to enhance system performance. The novel integrated PIN diode array design yields a high date rate of 1.2 Gbit s-1 by 16QAM-OFDM based on a commercially available RGB LED in a VLC system with bit error rate under a 7% pre-forward-error-correction (FEC) threshold of 3.8 × 10-3 after 30 cm free-space transmission. The results show that the use of integrated antennas in VLC systems will become a trend in the future.

  11. Control system design for nano-positioning using piezoelectric actuators

    NASA Astrophysics Data System (ADS)

    Shan, Jinjun; Liu, Yanfang; Gabbert, Ulrich; Cui, Naigang

    2016-02-01

    This paper presents a systematic control system design for nano-positioning of a piezoelectric actuator (PEA). PEAs exhibit hysteresis nonlinearity, which can dramatically limit the application and performance of linear feedback control theory. Thus the hysteresis is compensated for based on the Maxwell resistive capacitor (MRC) model first. Then a proportional plus integral (PI) controller and a proportional double integral plus lead compensation (PII&L) controller are designed for the hysteresis-compensated PEA to account for model uncertainty, disturbance, and noise. The robust stability of both controllers is proved. The effectiveness of the proposed control scheme is demonstrated experimentally. Both controllers achieve fast precise positioning. The 2% settling times for the PI controller and the PII&L controller are 1.5 ms and 4.7 ms, respectively. The positioning resolution is upto 1 nm for both controllers.

  12. EPA (Environmental Protection Agency) method study 25, method 602, purgeable aromatics. Report for Sep 79-Dec 82

    SciTech Connect

    Warner, B.J.; Finke, J.M.; Gable, R.C.; Strobel, J.E.; Snyder, A.D.

    1984-05-01

    The experimental design and the results of an interlaboratory study for an analytical method to detect purgeable aromatics in water are described herein. The method, EPA Method 602, Purgeable Aromatics, employs a purge-and-trap chromatographic technique for determination of seven aromatic hydrocarbon analytes in water matrices. The three Youden pairs of spiking solutions used in this study contained benzene, chlorobenzene, 1,2-dichlorobenzene, 1,3-dichlorobenzene, 1,4-dichlorobenzene, ethylbenzene and toluene. The six water types used in the study were distilled water, drinking water, surface water, and three wastewater samples from industries employing or producing aromatic hydrocarbons. Twenty laboratories participated in the Method 602 validation study. The participating laboratories supplied their individual distilled, drinking, and surface water samples. Monsanto Research Corporation (MRC) supplied the three industrial wastewater samples. The statistical analyses and conclusions reached in this report are based on the analytical data obtained by the 20 participating laboratories.

  13. Cell scientist to watch - Emmanuel Boucrot.

    PubMed

    2016-09-01

    Emmanuel Boucrot obtained an undergraduate and a master's degree in biochemistry at the University of Geneva in Switzerland. He pursued his PhD in immunology at the University of Aix-Marseille II in France, supervised by Stéphane Méresse in the laboratory of Jean-Pierre Gorvel. Emmanuel moved to the USA for his postdoctoral training in the laboratory of Tomas Kirchhausen at Harvard Medical School, first as an EMBO fellow and then as a Human Frontiers Science Program fellow. Before starting his own laboratory in 2011, Emmanuel held another postdoctoral position in the laboratory of Harvey McMahon at the MRC Laboratory of Molecular Biology in Cambridge, UK. He is a recipient of a Lister Institute Research Prize and a BBSRC David Phillips Research Fellowship. His group at University College London is interested in studying the mechanisms of clathrin-independent endocytosis, as well as investigating properties of quiescent cells. PMID:27587837

  14. Antimicrobial prenylated benzoylphloroglucinol derivatives and xanthones from the leaves of Garcinia goudotiana.

    PubMed

    Mahamodo, Sania; Rivière, Céline; Neut, Christel; Abedini, Amin; Ranarivelo, Heritiana; Duhal, Nathalie; Roumy, Vincent; Hennebelle, Thierry; Sahpaz, Sevser; Lemoine, Amélie; Razafimahefa, Dorothée; Razanamahefa, Bakonirina; Bailleul, François; Andriamihaja, Bakolinirina

    2014-06-01

    Bioassay-guided fractionation using antimicrobial assay of the crude acetonic extract of Garcinia goudotiana leaves and of its five partitions led to the isolation of two new prenylated benzoylphloroglucinol derivatives, goudotianone 1 (1) and goudotianone 2 (2), in addition to two known compounds including one xanthone, 1,3,7-trihydroxy-2-isoprenylxanthone (3), and one triterpenoid, friedelin (4). Their structures were elucidated on the basis of different spectroscopic methods, including extensive 1D- and 2D-NMR spectroscopy and mass spectrometry. The crude acetonic extract, the methylene chloride and ethyl acetate partitions, and some tested compounds isolated from this species (1-3) demonstrated selective significant antimicrobial activities against Gram-positive bacteria, in particular Staphylococcus lugdunensis, Enterococcus faecalis and Mycobacterium smegmatis. The potential cytotoxic activities of these extracts and compounds were evaluated against human colon carcinoma HT29 and human fetal lung fibroblast MRC5 cells. PMID:24690454

  15. Reliable Cut-Through Forwarding for Inter-Vehicle Networks

    NASA Astrophysics Data System (ADS)

    Shagdar, Oyunchimeg; Shirazi, Mehdad. N.; Tang, Suhua; Suzuki, Ryutaro; Obana, Sadao

    In inter-vehicle networks, it is required that collision warning messages be distributed over multiple hops with significantly short delay. Cut-through packet forwarding is known to be an effective method to reduce forwarding latency. However, it suffers from the reliability issue, which is especially severe in highly mobile scenario, due to multi-path fading. This paper tries to establish a reliable cut-through forwarding scheme by applying diversity combining method to collision warning messages. By exploiting the nature of the multi-hop forwarding of a broadcast packet in CDMA wireless networks, the diversity combining scheme does not incur any additional communication overhead or delay. The simulation results show that diversity combining schemes, especially Maximal Ratio Combining (MRC), can effectively reduce BER by orders of magnitude.

  16. Conformationally constrained goniofufurone mimics as inhibitors of tumour cells growth: Design, synthesis and SAR study.

    PubMed

    Benedeković, Goran; Francuz, Jovana; Kovačević, Ivana; Popsavin, Mirjana; Zelenović, Bojana Srećo; Kojić, Vesna; Bogdanović, Gordana; Divjaković, Vladimir; Popsavin, Velimir

    2014-07-23

    Synthesis of conformationally restricted (+)-goniofufurone (1) and 7-epi-(+)-goniofufurone (2) analogues, with embedded O-isopropylidene, O-methylidene or cyclic carbonate functions is disclosed starting from d-glucose. A number of potential bioisosteres of 1 and 2 bearing both 5,7-O-methylidene and 4-substituted cinnamoyloxy functions at the C-7 position have also been synthesized. In vitro cytotoxicity of target molecules against a number of human tumour cell lines were recorded and compared with those observed for the parent molecules 1 and 2. Some of the analogues displayed powerful antiproliferative effects on selected human tumour cell lines, but all of them were devoid of any cytotoxicity towards the normal foetal lung fibroblasts (MRC-5). A SAR study reveals the structural features of these lactones that may increase their antiproliferative activity. PMID:24929342

  17. Heteroannelated and 7-deoxygenated goniofufurone mimics with antitumour activity: design, synthesis and preliminary SAR studies.

    PubMed

    Popsavin, Velimir; Francuz, Jovana; Srećo Zelenović, Bojana; Benedeković, Goran; Popsavin, Mirjana; Kojić, Vesna; Bogdanović, Gordana

    2013-10-15

    Cytotoxic (+)-goniofufurone mimic such as benzoxepane 2 was preferentially formed after the treatment of 7-O-benzoyl-5-O-benzyl (+)-goniofufurone derivative 6 with titanium(IV) fluoride. However, the corresponding 7-epimer 5 (derivative of 7-epi-goniofufurone) under the similar reaction conditions gave mainly 7-deoxy derivative 7 as a result of an unexpected 1,5-hydride shift. Extension of this methodology to the enantiomer ent-6 provided cytotoxic (-)-goniofufurone mimics ent-2 and ent-7. Synthesized compounds showed diverse growth inhibitory effects against selected tumour cell lines, but were devoid of any significant toxicity towards the normal foetal lung fibroblasts (MRC-5). A SAR study reveals the structural features of these lactones that are beneficial for their antiproliferative activity, such as presence of an additional oxepane ring, the absolute stereochemistry and the presence of a deoxy function at the C-7 position. PMID:24021462

  18. Gastric cancer: Current status of lymph node dissection.

    PubMed

    Degiuli, Maurizio; De Manzoni, Giovanni; Di Leo, Alberto; D'Ugo, Domenico; Galasso, Erica; Marrelli, Daniele; Petrioli, Roberto; Polom, Karol; Roviello, Franco; Santullo, Francesco; Morino, Mario

    2016-03-14

    D2 procedure has been accepted in Far East as the standard treatment for both early (EGC) and advanced gastric cancer (AGC) for many decades. Recently EGC has been successfully treated with endoscopy by endoscopic mucosal resection or endoscopic submucosal dissection, when restricted or extended Gotoda's criteria can be applied and D1+ surgery is offered only to patients not fitted for less invasive treatment. Furthermore, two randomised controlled trials (RCTs) have been demonstrating the non inferiority of minimally invasive technique as compared to standard open surgery for the treatment of early cases and recently the feasibility of adequate D1+ dissection has been demonstrated also for the robot assisted technique. In case of AGC the debate on the extent of nodal dissection has been open for many decades. While D2 gastrectomy was performed as the standard procedure in eastern countries, mostly based on observational and retrospective studies, in the west the Medical Research Council (MRC), Dutch and Italian RCTs have been conducted to show a survival benefit of D2 over D1 with evidence based medicine. Unfortunately both the MRC and the Dutch trials failed to show a survival benefit after the D2 procedure, mostly due to the significant increase of postoperative morbidity and mortality, which was referred to splenopancreatectomy. Only 15 years after the conclusion of its accrual, the Dutch trial could report a significant decrease of recurrence after D2 procedure. Recently the long term survival analysis of the Italian RCT could demonstrate a benefit for patients with positive nodes treated with D2 gastrectomy without splenopancreatectomy. As nowadays also in western countries D2 procedure can be done safely with pancreas preserving technique and without preventive splenectomy, it has been suggested in several national guidelines as the recommended procedure for patients with AGC. PMID:26973384

  19. MALAREO: a user-driven project.

    PubMed

    Gebreslasie, Michael T; Bauwens, Ides

    2015-01-01

    The aim of this study is to assess the capacity gaps and requirements of Earth observation (EO) and related technologies for malaria vector control and management in the Lubombo Spatial Development Initiative regions of South Africa, Swaziland and Mozambique. In order to achieve the core objective of this study, available EO data (including main characteristics and resources required to utilize them) and their potential applications for malaria epidemiology are reviewed. In addition, a survey was conducted to assess the availability of human and facility resources to operate EO and related technologies for control and management of the malaria control programs in these countries resulting in an analysis of capacity gaps, priorities and requirements. Earth observation in malaria vector control and management has two different applications: i) collection of relevant remotely sensed data for epidemiological use; and ii) direct support of ongoing malaria vector control activities. All malaria control programs and institutions recognize the significance of EO products to detect mosquito vector habitats, to monitor environmental parameters affecting mosquito vector populations as well as house mapping and distribution of information supporting residual spray planning and monitoring. It was found that only the malaria research unit (MRU) of the medical research council (MRC) in South Africa and the national malaria control program (MCP) in Swaziland currently have a fully functional geographic information systems (GIS), whereas the other surveyed MCPs in South Africa and Mozambique currently do not have this in place. Earth observation skills only exist in MRU of MRC, while spatial epidemiology is scarce in all institutions, which was identified as major gap. The survey has also confirmed that EO and GIS technologies have enormous potential as sources of spatial data and as analytical frameworks for malaria vector control. It is therefore evident that planning and

  20. Characteristics of Patients with Chronic Obstructive Pulmonary Disease at the First Visit to a Pulmonary Medical Center in Korea: The KOrea COpd Subgroup Study Team Cohort

    PubMed Central

    2016-01-01

    The Korea Chronic Obstructive Pulmonary Disorders Subgroup Study Team (Korea COPD Subgroup Study team, KOCOSS) is a multicenter observational study that includes 956 patients (mean age 69.9 ± 7.8 years) who were enrolled from 45 tertiary and university-affiliated hospitals from December 2011 to October 2014. The initial evaluation for all patients included pulmonary function tests (PFT), 6-minute walk distance (6MWD), COPD Assessment Test (CAT), modified Medical Research Council (mMRC) dyspnea scale, and the COPD-specific version of St. George’s Respiratory Questionnaire (SGRQ-C). Here, we report the comparison of baseline characteristics between patients with early- (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage I and II/groups A and B) and late-stage COPD (GOLD stage III and IV/groups C and D). Among all patients, the mean post-bronchodilator FEV1 was 55.8% ± 16.7% of the predicted value, and most of the patients were in GOLD stage II (520, 56.9%) and group B (399, 42.0%). The number of exacerbations during one year prior to the first visit was significantly lower in patients with early COPD (0.4 vs. 0.9/0.1 vs. 1.2), as were the CAT score (13.9 vs. 18.3/13.5 vs. 18.1), mMRC (1.4 vs. 2.0/1.3 vs.1.9), and SGRQ-C total score (30.4 vs. 42.9/29.1 vs. 42.6) compared to late-stage COPD (all P < 0.001). Common comorbidities among all patients were hypertension (323, 37.7%), diabetes mellitus (139, 14.8%), and depression (207, 23.6%). The data from patients with early COPD will provide important information towards early detection, proper initial management, and design of future studies. PMID:27051239

  1. Synthesis and Antibacterial Evaluation of a New Series of N-Alkyl-2-alkynyl/(E)-alkenyl-4-(1H)-quinolones

    PubMed Central

    Wube, Abraham; Guzman, Juan-David; Hüfner, Antje; Hochfellner, Christina; Blunder, Martina; Bauer, Rudolf; Gibbons, Simon; Bhakta, Sanjib; Bucar, Franz

    2012-01-01

    To gain further insight into the structural requirements of the aliphatic group at position 2 for their antimycobacterial activity, some N-alkyl-4-(1H)-quinolones bearing position 2 alkynyls with various chain length and triple bond positions were prepared and tested for in vitro antibacterial activity against rapidly-growing strains of mycobacteria, the vaccine strain Mycobacterium bovis BCG, and methicillin-resistant Staphylococcus aureus strains, EMRSA-15 and -16. The compounds were also evaluated for inhibition of ATP-dependent MurE ligase of Mycobacterium tuberculosis. The lowest MIC value of 0.5 mg/L (1.2-1.5 μM) was found against M. fortuitum and M. smegmatis. These compounds displayed no or only weak toxicity to the human lung fibroblast cell line MRC-5 at 100 μM concentration. The quinolone derivatives exhibited pronounced activity against the epidemic MRSA strains (EMRSA-15 and -16) with MIC values of 2-128 mg/L (5.3-364.7 μM), and M. bovis BCG with an MIC value of 25 mg/L (66.0-77.4 μM). In addition, the compounds inhibited the MurE ligase of M. tuberculosis with moderate to weak activity showing IC50 values of 200-774 μM. The increased selectivity towards mycobacterial bacilli with reference to MRC-5 cells observed for 2-alkynyl quinolones compared to their corresponding 2-alkenyl analogues serves to highlight the mycobacterial specific effect of the triple bond. Exploration of a terminal bromine atom at the side chain of N-alkyl-2-(E)-alkenyl-4-(1H)-quinolones showed improved antimycobacterial activity whereas a cyclopropyl residue at N-1 was suggested to be detrimental to antibacterial activity. PMID:22777190

  2. Nimesulide Silver Metallodrugs, Containing the Mitochondriotropic, Triaryl Derivatives of Pnictogen; Anticancer Activity against Human Breast Cancer Cells.

    PubMed

    Banti, Christina N; Papatriantafyllopoulou, Constantina; Manoli, Maria; Tasiopoulos, Anastasios J; Hadjikakou, Sotiris K

    2016-09-01

    Novel silver(I) metallo-drugs of the nonsteroidal anti-inflammatory drug nimesulide (nim) and the mitochondriotropic triaryl derivatives of pnictogen ligands (tpE, E = P (tpp, tptp, or totp), As (tpAs), Sb (tpSb)) with the formulas {[Ag(nim) (tpp)2]DMF} (1), [Ag(nim) (tptp)2] (2), [Ag(nim) (totp)] (3), [Ag(nim) (tpAs)2] (4), and [Ag(nim) (tpSb)3] (5) ((tpp = triphenyphosphine, tptp = tri(p-tolyl)phosphine, totp = tri(o-tolyl)phosphine, tpAs = triphenylarsine, tpSb = triphenylantimony, and DMF = dimethylformamide) were synthesized and characterized by melting point, vibrational spectroscopy (mid-Fourier transform IR), (1)H NMR, UV-visible spectroscopic techniques, and X-ray crystallography. The in vitro cytotoxic activity of 1-5 against human breast adenocarcinoma cancer cell lines: MCF-7 (estrogen receptor (ER) positive) and MDA-MB-231 (ER negative) was determined. The genotoxicity on normal human fetal lung fibroblast cells (MRC-5) caused by 1-5 was evaluated by fluorescence microscopy. The absence of micronucleus in MRC-5 cells confirms the in vitro non toxicity behavior of the compounds. Because of the morphology of the cells, an apoptotic pathway was concluded for the cell death. The apoptotic pathway, especially though the mitochondrion damage, was confirmed by DNA fragmentation, cell cycle arrest, and permeabilization of the mitochondrial membrane tests. The molecular mechanism of action of 1-5 was further studied by (i) the binding affinity of 1-5 toward the calf thymus (CT) DNA, (ii) the inhibitory activity of 1-5 against lipoxygenase (an enzyme that oxidizes polyunsaturated fatty acids to leukotrienes or prostaglandins), and (iii) the catalytic activity of 1-5 on the oxidation of linoleic acid (an acid that partakes in membrane fluidity, membrane enzyme activities, etc.) to hyperoxolinoleic acid by oxygen. PMID:27513311

  3. A novel non-mineral oil-based adjuvant. II. Efficacy of a synthetic sulfolipopolysaccharide in a squalane-in-water emulsion in pigs.

    PubMed

    Hilgers, L A; Platenburg, P L; Luitjens, A; Groenveld, B; Dazelle, T; Weststrate, M W

    1994-05-01

    The adjuvanticity of a sulfolipopolysaccharide (SLP) incorporated into a squalane-in-water emulsion (SLP/S/W) was compared with that of a mineral oil-in-water (O/W) adjuvant currently used in commercial porcine vaccines. Groups of pigs were immunized twice with vaccines comprising either inactivated influenza virus (iFlu3 containing strains A/Swine, MRC-11 and X-79), inactivated pseudorabies virus (iPRV), live pseudorabies virus (PRV) or inactivated porcine parvovirus (iPPV) as antigen and SLP/S/W or O/W as adjuvant. Antibody titres in serum 2 or 3 weeks after the second immunization were measured by haemagglutination inhibition (HI) or serum neutralization (SN) assays. Both adjuvants significantly augmented the antibody responses against the antigens tested. Mean factors of increase obtained by SLP/S/W and O/W were: 315 and 91, respectively, for A/Swine; 478 and 137 for MRC-11; 362 and 128 for X-79; 69 and 49 for iPRV; and 23 and 7 for live PRV. Increased humoral immunity against live PRV was affirmed by reduced levels and duration of virus excreted by pigs after challenge with virulent PRV. Immunization of pigs with iPPV plus adjuvant SLP/S/W gave 36-fold higher titres than with O/W. It was concluded that SLP/S/W is more effective than O/W in stimulating humoral immunity against the viral antigens examined and that the two constituents SLP and S/W interact synergistically. Advantages of SLP/S/W over O/W include stronger adjuvanticity, better biocompatibility and lower doses of active substances.

  4. A novel non-mineral oil-based adjuvant. I. Efficacy of a synthetic sulfolipopolysaccharide in a squalane-in-water emulsion in laboratory animals.

    PubMed

    Hilgers, L A; Platenburg, P L; Luitjens, A; Groenveld, B; Dazelle, T; Ferrari-Laloux, M; Weststrate, M W

    1994-05-01

    Sulfolipopolysaccharides (SLPs) were synthesized by reaction of the synthetic polysucrose polymer Ficoll-400 with chlorosulfonic acid and lauroyl chloride in anhydrous medium. Hydrophobic derivatives were obtained by addition of a small number of sulfate and a large number of lipid groups. Gel-permeation high-performance liquid chromatography (g.p.-h.p.l.c.) exhibited a wide range in molecular weight of both Ficoll-400 and SLP polymers. The calculated weight-average molecular weight (Mw) of Ficoll-400 and SLP using polystyrene polymers as references was 187,000 and 380,000 respectively, exhibiting a twofold increase in molecular weight upon derivatization. Adjuvanticity of hydrophobic SLPs with 0.2 sulfate and 1.5 lipid groups per sucrose monomer, a squalane-in-water emulsion (S/W), SLP incorporated into S/W (SLP/S/W), and a mineral oil-based emulsion (O/W) was investigated in combination with different antigens in mice and guinea-pigs. Antibody responses in serum against ovalbumin (OVA), dinitrophenylated bovine serum albumin (DNP-BSA), inactivated influenza virus strain MRC-11 (MRC-11), a mixture of three influenza virus strains (iFlu3) and inactivated pseudorabies virus (iPRV) were measured by either haemagglutination (HA), haemagglutination inhibition (HI) or serum neutralization (SN). Vaccines were prepared by simply mixing one volume of antigen with one volume of adjuvant solution. Antibody titres after one or two injections with these antigens were enhanced significantly by SLP/S/W, SLP, S/W and O/W and in most studies, SLP/S/W was demonstrated to be more effective than either the two constituent components or the O/W adjuvant.(ABSTRACT TRUNCATED AT 250 WORDS)

  5. A reinvestigation of recruitment to randomised, controlled, multicenter trials: a review of trials funded by two UK funding agencies

    PubMed Central

    2013-01-01

    Background Randomised controlled trials (RCTs) are the gold standard assessment for health technologies. A key aspect of the design of any clinical trial is the target sample size. However, many publicly-funded trials fail to reach their target sample size. This study seeks to assess the current state of recruitment success and grant extensions in trials funded by the Health Technology Assessment (HTA) program and the UK Medical Research Council (MRC). Methods Data were gathered from two sources: the National Institute for Health Research (NIHR) HTA Journal Archive and the MRC subset of the International Standard Randomised Controlled Trial Number (ISRCTN) register. A total of 440 trials recruiting between 2002 and 2008 were assessed for eligibility, of which 73 met the inclusion criteria. Where data were unavailable from the reports, members of the trial team were contacted to ensure completeness. Results Over half (55%) of trials recruited their originally specified target sample size, with over three-quarters (78%) recruiting 80% of their target. There was no evidence of this improving over the time of the assessment. Nearly half (45%) of trials received an extension of some kind. Those that did were no more likely to successfully recruit. Trials with 80% power were less likely to successfully recruit compared to studies with 90% power. Conclusions While recruitment appears to have improved since 1994 to 2002, publicly-funded trials in the UK still struggle to recruit to their target sample size, and both time and financial extensions are often requested. Strategies to cope with such problems should be more widely applied. It is recommended that where possible studies are planned with 90% power. PMID:23758961

  6. Mutations in NDUFB11, Encoding a Complex I Component of the Mitochondrial Respiratory Chain, Cause Microphthalmia with Linear Skin Defects Syndrome

    PubMed Central

    van Rahden, Vanessa A.; Fernandez-Vizarra, Erika; Alawi, Malik; Brand, Kristina; Fellmann, Florence; Horn, Denise; Zeviani, Massimo; Kutsche, Kerstin

    2015-01-01

    Microphthalmia with linear skin defects (MLS) syndrome is an X-linked male-lethal disorder also known as MIDAS (microphthalmia, dermal aplasia, and sclerocornea). Additional clinical features include neurological and cardiac abnormalities. MLS syndrome is genetically heterogeneous given that heterozygous mutations in HCCS or COX7B have been identified in MLS-affected females. Both genes encode proteins involved in the structure and function of complexes III and IV, which form the terminal segment of the mitochondrial respiratory chain (MRC). However, not all individuals with MLS syndrome carry a mutation in either HCCS or COX7B. The majority of MLS-affected females have severe skewing of X chromosome inactivation, suggesting that mutations in HCCS, COX7B, and other as-yet-unidentified X-linked gene(s) cause selective loss of cells in which the mutated X chromosome is active. By applying whole-exome sequencing and filtering for X-chromosomal variants, we identified a de novo nonsense mutation in NDUFB11 (Xp11.23) in one female individual and a heterozygous 1-bp deletion in a second individual, her asymptomatic mother, and an affected aborted fetus of the subject’s mother. NDUFB11 encodes one of 30 poorly characterized supernumerary subunits of NADH:ubiquinone oxidoreductase, known as complex I (cI), the first and largest enzyme of the MRC. By shRNA-mediated NDUFB11 knockdown in HeLa cells, we demonstrate that NDUFB11 is essential for cI assembly and activity as well as cell growth and survival. These results demonstrate that X-linked genetic defects leading to the complete inactivation of complex I, III, or IV underlie MLS syndrome. Our data reveal an unexpected role of cI dysfunction in a developmental phenotype, further underscoring the existence of a group of mitochondrial diseases associated with neurocutaneous manifestations. PMID:25772934

  7. Mutations in NDUFB11, encoding a complex I component of the mitochondrial respiratory chain, cause microphthalmia with linear skin defects syndrome.

    PubMed

    van Rahden, Vanessa A; Fernandez-Vizarra, Erika; Alawi, Malik; Brand, Kristina; Fellmann, Florence; Horn, Denise; Zeviani, Massimo; Kutsche, Kerstin

    2015-04-01

    Microphthalmia with linear skin defects (MLS) syndrome is an X-linked male-lethal disorder also known as MIDAS (microphthalmia, dermal aplasia, and sclerocornea). Additional clinical features include neurological and cardiac abnormalities. MLS syndrome is genetically heterogeneous given that heterozygous mutations in HCCS or COX7B have been identified in MLS-affected females. Both genes encode proteins involved in the structure and function of complexes III and IV, which form the terminal segment of the mitochondrial respiratory chain (MRC). However, not all individuals with MLS syndrome carry a mutation in either HCCS or COX7B. The majority of MLS-affected females have severe skewing of X chromosome inactivation, suggesting that mutations in HCCS, COX7B, and other as-yet-unidentified X-linked gene(s) cause selective loss of cells in which the mutated X chromosome is active. By applying whole-exome sequencing and filtering for X-chromosomal variants, we identified a de novo nonsense mutation in NDUFB11 (Xp11.23) in one female individual and a heterozygous 1-bp deletion in a second individual, her asymptomatic mother, and an affected aborted fetus of the subject's mother. NDUFB11 encodes one of 30 poorly characterized supernumerary subunits of NADH:ubiquinone oxidoreductase, known as complex I (cI), the first and largest enzyme of the MRC. By shRNA-mediated NDUFB11 knockdown in HeLa cells, we demonstrate that NDUFB11 is essential for cI assembly and activity as well as cell growth and survival. These results demonstrate that X-linked genetic defects leading to the complete inactivation of complex I, III, or IV underlie MLS syndrome. Our data reveal an unexpected role of cI dysfunction in a developmental phenotype, further underscoring the existence of a group of mitochondrial diseases associated with neurocutaneous manifestations.

  8. Low immunogenicity of allogeneic human umbilical cord blood-derived mesenchymal stem cells in vitro and in vivo

    SciTech Connect

    Lee, Miyoung; Jeong, Sang Young; Ha, Jueun; Kim, Miyeon; Jin, Hye Jin; Kwon, Soon-Jae; Chang, Jong Wook; Choi, Soo Jin; Oh, Wonil; Yang, Yoon Sun; Kim, Jae-Sung; Jeon, Hong Bae

    2014-04-18

    Highlights: • hUCB-MSCs maintained low immunogenicity even after immune challenge in vitro. • Humanized NSG mice were established using human UCB CD34+ cells. • Repeated intravenous hUCB-MSC injection into mice did not lead to immune responses and adverse events. • Allogeneic hUCB-MSCs maintained low immunogenicity in vitro and in vivo. - Abstract: Evaluation of the immunogenicity of human mesenchymal stem cells (MSCs) in an allogeneic setting during therapy has been hampered by lack of suitable models due to technical and ethical limitations. Here, we show that allogeneic human umbilical cord blood derived-MSCs (hUCB-MSCs) maintained low immunogenicity even after immune challenge in vitro. To confirm these properties in vivo, a humanized mouse model was established by injecting isolated hUCB-derived CD34+ cells intravenously into immunocompromised NOD/SCID IL2γnull (NSG) mice. After repeated intravenous injection of human peripheral blood mononuclear cells (hPBMCs) or MRC5 cells into these mice, immunological alterations including T cell proliferation and increased IFN-γ, TNF-α, and human IgG levels, were observed. In contrast, hUCB-MSC injection did not elicit these responses. While lymphocyte infiltration in the lung and small intestine and reduced survival rates were observed after hPBMC or MRC5 transplantation, no adverse events were observed following hUCB-MSC introduction. In conclusion, our data suggest that allogeneic hUCB-MSCs have low immunogenicity in vitro and in vivo, and are therefore “immunologically safe” for use in allogeneic clinical applications.

  9. Epigenetic modulation upon exposure of lung fibroblasts to TiO2 and ZnO nanoparticles: alterations in DNA methylation

    PubMed Central

    Patil, Nayana A; Gade, WN; Deobagkar, Deepti D

    2016-01-01

    Titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles (NPs) are promising candidates for numerous applications in consumer products. This will lead to increased human exposure, thus posing a threat to human health. Both these types of NPs have been studied for their cell toxicity, immunotoxicity, and genotoxicity. However, effects of these NPs on epigenetic modulations have not been studied. Epigenetics is an important link in the genotype and phenotype modulation and misregulation can often lead to lifestyle diseases. In this study, we have evaluated the DNA methylation-based epigenetic changes upon exposure to various concentrations of NPs. The investigation was designed to evaluate global DNA methylation, estimating the corresponding methyltransferase activity and expression of Dnmt gene using lung fibroblast (MRC5) cell line as lungs are the primary route of entry and target of occupational exposure to TiO2 and ZnO NPs. Enzyme-linked immunosorbent assay-based immunochemical assay revealed dose-related decrease in global DNA methylation and DNA methyltransferase activity. We also found direct correlation between the concentration of NPs, global methylation levels, and expression levels of Dnmt1, 3A, and 3B genes upon exposure. This is the first study to investigate effect of exposure to TiO2 and ZnO on DNA methylation levels in MRC5 cells. Epigenetic processes are known to play an important role in reprogramming and adaptation ability of an organism and can have long-term consequences. We suggest that changes in DNA methylation can serve as good biomarkers for early exposure to NPs since they occur at concentrations well below the sublethal levels. Our results demonstrate a clear epigenetic alteration in response to metal oxide NPs and that this effect was dose-dependent.

  10. Autosomal-recessive cerebellar ataxia caused by a novel ADCK3 mutation that elongates the protein: clinical, genetic and biochemical characterisation

    PubMed Central

    Liu, Yo-Tsen; Hersheson, Joshua; Plagnol, Vincent; Fawcett, Katherine; Duberley, Kate E C; Preza, Elisavet; Hargreaves, Iain P; Chalasani, Annapurna; Laurá, Matilde; Wood, Nick W; Reilly, Mary M; Houlden, Henry

    2014-01-01

    Background The autosomal-recessive cerebellar ataxias (ARCA) are a clinically and genetically heterogeneous group of neurodegenerative disorders. The large number of ARCA genes leads to delay and difficulties obtaining an exact diagnosis in many patients and families. Ubiquinone (CoQ10) deficiency is one of the potentially treatable causes of ARCAs as some patients respond to CoQ10 supplementation. The AarF domain containing kinase 3 gene (ADCK3) is one of several genes associated with CoQ10 deficiency. ADCK3 encodes a mitochondrial protein which functions as an electron-transfer membrane protein complex in the mitochondrial respiratory chain (MRC). Methods We report two siblings from a consanguineous Pakistani family who presented with cerebellar ataxia and severe myoclonus from adolescence. Whole exome sequencing and biochemical assessment of fibroblasts were performed in the index patient. Results A novel homozygous frameshift mutation in ADCK3 (p.Ser616Leufs*114), was identified in both siblings. This frameshift mutation results in the loss of the stop codon, extending the coding protein by 81 amino acids. Significant CoQ10 deficiency and reduced MRC enzyme activities in the index patient's fibroblasts suggested that the mutant protein may reduce the efficiency of mitochondrial electron transfer. CoQ10 supplementation was initiated following these genetic and biochemical analyses. She gained substantial improvement in myoclonic movements, ataxic gait and dysarthric speech after treatment. Conclusion This study highlights the importance of diagnosing ADCK3 mutations and the potential benefit of treatment for patients. The identification of this new mutation broadens the phenotypic spectrum associated with ADCK3 mutations and provides further understanding of their pathogenic mechanism. PMID:24218524

  11. A Screening Study to Determine the Prevalence of Airway Disease in Heroin Smokers.

    PubMed

    Lewis-Burke, Nadia; Vlies, Ben; Wooding, Olivia; Davies, Lisa; Walker, Paul P

    2016-06-01

    Over the last 20 years smoking has become the most common method of heroin use and increasing numbers of heroin smokers are presenting to local medical services, before the age of 40 years, with severe airway disease. To determine COPD prevalence we recruited 129 subjects from two local community drug services, of whom 107 were heroin smokers. We collected demographic, medical and treatment data, smoking history (including cannabis and opiates) and details of symptoms including MRC dyspnoea. Subjects completed the COPD Assessment Tool and spirometry. Thirty heroin smokers were identified as having COPD resulting in a COPD prevalence of 28%. Mean age was 43 (4) years and FEV1 was 2.71 (0.98) L; 70 (23) %predicted. Breathlessness and wheeze were more common in subjects with COPD (p < 0.04 and p < 0.05) but symptoms were common in all heroin smokers. MRC score was higher (3 vs. 2.4; p < 0.04) in those with COPD and health status appeared poorer (CAT 20.4 vs. 15.8; p < 0.07). Only 4 (11%) had previously been diagnosed with COPD and only 16 (53%) received any inhaled medication. Asthma prevalence was also high at 33% and asthmatic subjects had similar symptoms and health status compared with the COPD subjects, and were also significantly undertreated. COPD and asthma are common in current and former heroin smokers. They are often present at a young age and are underdiagnosed and undertreated. Awareness of this issue should be highlighted within drug services and in particular to heroin smokers. Screening this high-risk population with spirometry should be considered. PMID:26701201

  12. Synthesis, Characterization, and Cytotoxicity of Platinum(IV) Carbamate Complexes

    PubMed Central

    Wilson, Justin J.; Lippard, Stephen J.

    2011-01-01

    The synthesis, characterization, and cytotoxicity of eight new platinum(IV) complexes having the general formula, c,c,t-[Pt(NH3)2Cl2(O2CNHR)2], are reported, where R = tert-butyl (4), cyclopentyl (5), cyclohexyl (6), phenyl (7), p-tolyl (8), p-anisole (9), 4-fluorophenyl (10), or 1-naphthyl (11). These compounds were synthesized by reacting organic isocyanates with the platinum(IV) complex, c,c,t-[Pt(NH3)2Cl2(OH)2]. The electrochemistry of the compounds was investigated by cyclic voltammetry. The aryl carbamate complexes 7 – 11 exhibit reduction peak potentials near −720 mV vs. Ag/AgCl, whereas the alkyl carbamate complexes display reduction peak potentials between −820 and −850 mV vs. Ag/AgCl. The cyclic voltammograms of c,c,t-[Pt(NH3)2Cl2(O2CCH3)2] (1), c,c,t-[Pt(NH3)2Cl2(O2CCF3)2] (2), and cis-[Pt(NH3)2Cl4] (3) were measured for comparison. Density functional theory (DFT) studies were undertaken to investigate the electronic structures of 1 – 11 and to determine their adiabatic electron affinities. A linear correlation (R2 = 0.887) between computed adiabatic electron affinities and measured reduction peak potential was discovered. The biological activity of 4 – 11 and, for comparison, cisplatin was evaluated in human lung cancer A549 and normal MRC-5 cells by the MTT assay. The compounds exhibit comparable or slightly better activity than cisplatin against the A549 cells. In MRC-5 cells, all are equally or slightly less cytotoxic than cisplatin, except for 4 and 5, which are more toxic. PMID:21361279

  13. The Toll-Like Receptor 5 Agonist Entolimod Mitigates Lethal Acute Radiation Syndrome in Non-Human Primates

    PubMed Central

    Krivokrysenko, Vadim I.; Toshkov, Ilia A.; Gleiberman, Anatoli S.; Krasnov, Peter; Shyshynova, Inna; Bespalov, Ivan; Maitra, Ratan K.; Narizhneva, Natalya V.; Singh, Vijay K.; Whitnall, Mark H.; Purmal, Andrei A.; Shakhov, Alexander N.; Gudkov, Andrei V.; Feinstein, Elena

    2015-01-01

    There are currently no approved medical radiation countermeasures (MRC) to reduce the lethality of high-dose total body ionizing irradiation expected in nuclear emergencies. An ideal MRC would be effective even when administered well after radiation exposure and would counteract the effects of irradiation on the hematopoietic system and gastrointestinal tract that contribute to its lethality. Entolimod is a Toll-like receptor 5 agonist with demonstrated radioprotective/mitigative activity in rodents and radioprotective activity in non-human primates. Here, we report data from several exploratory studies conducted in lethally irradiated non-human primates (rhesus macaques) treated with a single intramuscular injection of entolimod (in the absence of intensive individualized supportive care) administered in a mitigative regimen, 1–48 hours after irradiation. Following exposure to LD50-70/40 of radiation, injection of efficacious doses of entolimod administered as late as 25 hours thereafter reduced the risk of mortality 2-3-fold, providing a statistically significant (P<0.01) absolute survival advantage of 40–60% compared to vehicle treatment. Similar magnitude of survival improvement was also achieved with drug delivered 48 hours after irradiation. Improved survival was accompanied by predominantly significant (P<0.05) effects of entolimod administration on accelerated morphological recovery of hematopoietic and immune system organs, decreased severity and duration of thrombocytopenia, anemia and neutropenia, and increased clonogenic potential of the bone marrow compared to control irradiated animals. Entolimod treatment also led to reduced apoptosis and accelerated crypt regeneration in the gastrointestinal tract. Together, these data indicate that entolimod is a highly promising potential life-saving treatment for victims of radiation disasters. PMID:26367124

  14. In Vitro Evaluation of 3-Arylcoumarin Derivatives in A549 Cell Line

    PubMed Central

    MUSA, MUSILIYU A.; JOSEPH, MOISE Y.; LATINWO, LEKAN M.; BADISA, VEERA; COOPERWOOD, JOHN S.

    2016-01-01

    Coumarins are naturally-occurring compounds with diverse and interesting biological activities. In the present study, we evaluated the in vitro cytotoxic effect of 8-(acetyloxy)-3-[4-(acetyloxy)phenyl]-2-oxo-2H-chromen-7-yl acetate (6); 8-(acetyloxy)-3-(4-methanesulfonyl phenyl)-2-oxo-2H-chromen-7-yl acetate (7); 4-(2-oxo-2H-chromen-3-yl)phenyl acetate (8); 3-(4-methanesulfonylphenyl)-2H-chromen-2-one (9); 4-(4-methyl-2-oxo-2H-chromen-3-yl)phenyl acetate (10); 3-(4-methanesulfonylphenyl)-4-methyl-2H-chromen-2-one (11); 8-(acetyloxy)-3-[4-(acetyloxy)phenyl]-4-methyl-2-oxo-2H-chromen-7-yl acetate (12); and 5-(acetyloxy)-3-[4-(acetyloxy) phenyl]-2-oxo-2H-chromen-7-yl acetate (13) in human lung (A549) cancer and normal lung (MRC-9) cell lines at different concentrations for 48 h using crystal violet dye binding assay. The cytotoxic effect of these coumarin derivatives were compared to the standard drug, docetaxel. Furthermore, the effect of the most active compound on the cell-cycle using propidium iodide, mitochondrial membrane potential (MMP) using tetramethyl rhodamine methyl ester (rhodamine-123) and reactive oxygen species (ROS) production using 2′,7′-dichlorofluorescin diacetate (PCFDA) were also evaluated. Results Compound 7 had the greatest cytotoxic effect (cytotoxic concentration, CC50=24 μM) and selectivity (MRC-9; CC50 >100 μM; inactive) in the A549 cell line, and caused cells to arrest in the S phase of the cell cycle, loss of MMP and increased ROS production in a concentration-dependent manner. Conclusion These findings suggest that compound 7 could serve as a new lead for the development of novel synthetic compounds with enhanced anticancer activity. PMID:25667442

  15. A CO-rich merger shaping a powerful and hyperluminous infrared radio galaxy at z = 2: the Dragonfly Galaxy

    NASA Astrophysics Data System (ADS)

    Emonts, B. H. C.; Mao, M. Y.; Stroe, A.; Pentericci, L.; Villar-Martín, M.; Norris, R. P.; Miley, G.; De Breuck, C.; van Moorsel, G. A.; Lehnert, M. D.; Carilli, C. L.; Röttgering, H. J. A.; Seymour, N.; Sadler, E. M.; Ekers, R. D.; Drouart, G.; Feain, I.; Colina, L.; Stevens, J.; Holt, J.

    2015-07-01

    In the low-redshift Universe, the most powerful radio sources are often associated with gas-rich galaxy mergers or interactions. We here present evidence for an advanced, gas-rich (`wet') merger associated with a powerful radio galaxy at a redshift of z ˜ 2. This radio galaxy, MRC 0152-209, is the most infrared-luminous high-redshift radio galaxy known in the Southern hemisphere. Using the Australia Telescope Compact Array, we obtained high-resolution CO(1-0) data of cold molecular gas, which we complement with Hubble Space Telescope (HST)/Wide Field Planetary Camera 2 (WFPC2) imaging and William Herschel Telescope long-slit spectroscopy. We find that, while roughly MH2 ˜ 2 × 1010 M⊙ of molecular gas coincides with the central host galaxy, another MH2 ˜ 3 × 1010 M⊙ is spread across a total extent of ˜60 kpc. Most of this widespread CO(1-0) appears to follow prominent tidal features visible in the rest-frame near-UV HST/WFPC2 imaging. Lyα emission shows an excess over He II, but a deficiency over LIR, which is likely the result of photoionization by enhanced but very obscured star formation that was triggered by the merger. In terms of feedback, the radio source is aligned with widespread CO(1-0) emission, which suggests that there is a physical link between the propagating radio jets and the presence of cold molecular gas on scales of the galaxy's halo. Its optical appearance, combined with the transformational stage at which we witness the evolution of MRC 0152-209, leads us to adopt the name `Dragonfly Galaxy'.

  16. Selenoprotein H Suppresses Cellular Senescence through Genome Maintenance and Redox Regulation*

    PubMed Central

    Wu, Ryan T. Y.; Cao, Lei; Chen, Benjamin P. C.; Cheng, Wen-Hsing

    2014-01-01

    Oxidative stress and persistent DNA damage response contribute to cellular senescence, a degeneration process critically involving ataxia telangiectasia-mutated (ATM) and p53. Selenoprotein H (SelH), a nuclear selenoprotein, is proposed to carry redox and transactivation domains. To determine the role of SelH in genome maintenance, shRNA knockdown was employed in human normal and immortalized cell lines. SelH shRNA MRC-5 diploid fibroblasts under ambient O2 displayed a distinct profile of senescence including β-galactosidase expression, autofluorescence, growth inhibition, and ATM pathway activation. Such senescence phenotypes were alleviated in the presence of ATM kinase inhibitors, by p53 shRNA knockdown, or by maintaining the cells under 3% O2. During the course of 5-day recovery, the induction of phospho-ATM on Ser-1981 and γH2AX by H2O2 treatment (20 μm) subsided in scrambled shRNA but exacerbated in SelH shRNA MRC-5 cells. Results from clonogenic assays demonstrated hypersensitivity of SelH shRNA HeLa cells to paraquat and H2O2, but not to hydroxyurea, neocarzinostatin, or camptothecin. While SelH mRNA expression was induced by H2O2 treatment, SelH-GFP did not mobilize to sites of oxidative DNA damage. The glutathione level was lower in SelH shRNA than scrambled shRNA HeLa cells, and the H2O2-induced cell death was rescued in the presence of N-acetylcysteine, a glutathione precursor. Altogether, SelH protects against cellular senescence to oxidative stress through a genome maintenance pathway involving ATM and p53. PMID:25336634

  17. Epigenetic modulation upon exposure of lung fibroblasts to TiO2 and ZnO nanoparticles: alterations in DNA methylation

    PubMed Central

    Patil, Nayana A; Gade, WN; Deobagkar, Deepti D

    2016-01-01

    Titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles (NPs) are promising candidates for numerous applications in consumer products. This will lead to increased human exposure, thus posing a threat to human health. Both these types of NPs have been studied for their cell toxicity, immunotoxicity, and genotoxicity. However, effects of these NPs on epigenetic modulations have not been studied. Epigenetics is an important link in the genotype and phenotype modulation and misregulation can often lead to lifestyle diseases. In this study, we have evaluated the DNA methylation-based epigenetic changes upon exposure to various concentrations of NPs. The investigation was designed to evaluate global DNA methylation, estimating the corresponding methyltransferase activity and expression of Dnmt gene using lung fibroblast (MRC5) cell line as lungs are the primary route of entry and target of occupational exposure to TiO2 and ZnO NPs. Enzyme-linked immunosorbent assay-based immunochemical assay revealed dose-related decrease in global DNA methylation and DNA methyltransferase activity. We also found direct correlation between the concentration of NPs, global methylation levels, and expression levels of Dnmt1, 3A, and 3B genes upon exposure. This is the first study to investigate effect of exposure to TiO2 and ZnO on DNA methylation levels in MRC5 cells. Epigenetic processes are known to play an important role in reprogramming and adaptation ability of an organism and can have long-term consequences. We suggest that changes in DNA methylation can serve as good biomarkers for early exposure to NPs since they occur at concentrations well below the sublethal levels. Our results demonstrate a clear epigenetic alteration in response to metal oxide NPs and that this effect was dose-dependent. PMID:27660443

  18. Comparative analysis of telomere length, telomerase and reverse transcriptase activity in human dental stem cells.

    PubMed

    Jeon, Byeong-Gyun; Kang, Eun-Ju; Kumar, B Mohana; Maeng, Geun-Ho; Ock, Sun-A; Kwack, Dae-Oh; Park, Bong-Wook; Rho, Gyu-Jin

    2011-01-01

    Stem cells from dental tissues have been isolated and established for tooth regenerative applications. However, basic characterization on their biological properties still needs to be investigated before employing them for effective clinical trials. In this study, we compared the telomere length, relative telomerase activity (RTA), and relative reverse transcriptase activity (RRA) as well as the surface antigen profile and mesenchymal differentiation ability in human dental papilla stem cells (DPaSCs), dental pulp stem cells (DPuSCs), and dental follicle stem cells (DFSCs) with mesenchymal stem cells (MSCs) derived from bone marrow. Dental stem cells (DSCs) were strongly positive for cell surface markers, such as CD44 and CD90. However, slightly lower expression of CD105 was observed in DPaSCs and DPuSCs compared to DFSCs and MSCs. Following specific induction, DPaSCs, DFSCs, and MSCs were successfully differentiated into adipocytes and osteocytes. However, DPuSCS, in particular, were able to differentiate into adipocytes but failed to induce into osteogenic differentiation. Further, all DSCs, MSCs, and MRC-5 fibroblasts as control were investigated for telomere length by nonradioactive chemiluminescent assay, RTA by relative-quantitative telomerase repeat amplification protocol (RQ-TRAP), and RRA by PCR-based assay. Mean telomere lengths in DPaSCs, DPuSCs, DFSCs, and MSCs was ∼11 kb, and the values did not differ significantly (p < 0.05) among the cells analyzed. RTA levels in DPaSCs were significantly (p < 0.05) higher than in MSCs, DPuSCs, DFSCs, and MRC-5 fibroblasts and among DSCs, DFSCs showed a significantly (p < 0.05) lower RTA. Moreover, RRA levels were significantly (p < 0.05) higher in DPaSCs, DPuSCs, and MSCs than in DFSCs. Based on these observations, we conclude that among DSCs, DPaSCs possessed ideal characteristics on telomere length, telomerase activity and reverse transcriptase (RTase) activity, and may serve as suitable alternative candidates

  19. Mutations in NDUFB11, encoding a complex I component of the mitochondrial respiratory chain, cause microphthalmia with linear skin defects syndrome.

    PubMed

    van Rahden, Vanessa A; Fernandez-Vizarra, Erika; Alawi, Malik; Brand, Kristina; Fellmann, Florence; Horn, Denise; Zeviani, Massimo; Kutsche, Kerstin

    2015-04-01

    Microphthalmia with linear skin defects (MLS) syndrome is an X-linked male-lethal disorder also known as MIDAS (microphthalmia, dermal aplasia, and sclerocornea). Additional clinical features include neurological and cardiac abnormalities. MLS syndrome is genetically heterogeneous given that heterozygous mutations in HCCS or COX7B have been identified in MLS-affected females. Both genes encode proteins involved in the structure and function of complexes III and IV, which form the terminal segment of the mitochondrial respiratory chain (MRC). However, not all individuals with MLS syndrome carry a mutation in either HCCS or COX7B. The majority of MLS-affected females have severe skewing of X chromosome inactivation, suggesting that mutations in HCCS, COX7B, and other as-yet-unidentified X-linked gene(s) cause selective loss of cells in which the mutated X chromosome is active. By applying whole-exome sequencing and filtering for X-chromosomal variants, we identified a de novo nonsense mutation in NDUFB11 (Xp11.23) in one female individual and a heterozygous 1-bp deletion in a second individual, her asymptomatic mother, and an affected aborted fetus of the subject's mother. NDUFB11 encodes one of 30 poorly characterized supernumerary subunits of NADH:ubiquinone oxidoreductase, known as complex I (cI), the first and largest enzyme of the MRC. By shRNA-mediated NDUFB11 knockdown in HeLa cells, we demonstrate that NDUFB11 is essential for cI assembly and activity as well as cell growth and survival. These results demonstrate that X-linked genetic defects leading to the complete inactivation of complex I, III, or IV underlie MLS syndrome. Our data reveal an unexpected role of cI dysfunction in a developmental phenotype, further underscoring the existence of a group of mitochondrial diseases associated with neurocutaneous manifestations. PMID:25772934

  20. Characterizing the mechanism of thiazolidinedione-induced hepatotoxicity: An in vitro model in mitochondria

    SciTech Connect

    Hu, Dan; Wu, Chun-qi; Li, Ze-jun; Liu, Yue; Fan, Xing; Wang, Quan-jun; Ding, Ri-gao

    2015-04-15

    Objective: To characterize the mechanism of action of thiazolidinedione (TZD)-induced liver mitochondrial toxicity caused by troglitazone, rosiglitazone, and pioglitazone in HepaRG cells. Methods: Human hepatoma cells (HepaRG) were treated with troglitazone, rosiglitazone, or pioglitazone (12.5, 25, and 50 μM) for 48 h. The Seahorse Biosciences XF24 Flux Analyzer was used to measure mitochondrial oxygen consumption. The effect of TZDs on reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected by flow cytometry. The mitochondrial ultrastructure of HepaRG cells was observed under a transmission electrical microscope (TEM). mtDNA content was evaluated by real-time PCR, and ATP content and mitochondrial respiratory chain (MRC) complex I, II, III, IV activity were measured via chemiluminescence. Results were considered statistically significant at p < 0.05. Results: Among the three drugs, troglitazone exhibited the highest potency, followed by rosiglitazone, and then pioglitazone. The TZDs caused varying degrees of mitochondrial respiratory function disorders including decreases in oxygen consumption, MRC activity, and ATP level, and an elevation in ROS level. TZD treatment resulted in mtDNA content decline, reduction in MMP, and alterations of mitochondrial structure. Conclusion: All investigated TZDs show a certain degree of mitochondrial toxicity, with troglitazone exhibiting the highest potency. The underlying mechanism of TZD-induced hepatotoxicity may be associated with alterations in mitochondrial respiratory function disorders, oxidative stress, and changes in membrane permeability. These parameters may be used early in drug development to further optimize risk:benefit profiles. - Highlights: • We compared three TZD mitochondrial toxicity characteristics in HepaRG cells. • TZD induced respiratory disorders and mitochondrial structural damage. • Mitochondrial toxicity evaluation presents guidance value for hepatotoxicity.

  1. Comparative study on oviposition and larval preference of spotted bollworm, Earias vittella on Bt and non-Bt cotton.

    PubMed

    Shera, P S; Arora, Ramesh

    2016-01-01

    Oviposition and larval preference of spotted bollworm, Earias vittella (Fabricius) was assessed on four transgenic Bt cotton hybrids, viz. MRC 6304 Bt (cry1Ac gene), JKCH 1947 Bt (modified cry1Ac gene), NCEH 6R Bt (cry1Ab/cry1Ac fused gene) and MRC 7017 BG II (cry1Ac and cry2Ab genes) in comparison to the respective isogenic cotton. The results showed that Bt toxin did not deter oviposition preference of E. vittella moths as there was no significant difference in the number of eggs laid on squares/bolls of Bt and non-Bt cotton hybrids, across different crop growth stages. There was also no behavioral change in larval preference with respect to selecting non-Bt cotton in comparison to Bt cotton. Floral bodies from Bt and the respective isogenic cotton genotypes were equally preferred by both first and third instar larvae after 24 hrs indicating that initial selection was independent of susceptibility to Bt toxin. However, E. vittella larvae showed significant difference in preference for different cotton genotypes. Studies on the relative preference indicated that third instar larvae had greater preference for bolls (7.29-7.50%) than for the squares (5.0-5.21%) and reverse was true for the first instar larvae which showed greater preference for squares (7.08-7.29%) than for the bolls (5.21-5.42%), in a multiple-choice test. It may be concluded that oviposition and larval preference of E. vittella did not differ significantly between Bt and isogenic non-Bt cotton genotypes.

  2. Phyllostachys edulis extract induces apoptosis signaling in osteosarcoma cells, associated with AMPK activation

    PubMed Central

    Chou, Chi-Wen; Cheng, Ya-Wen; Tsai, Chung-Hung

    2014-01-01

    Objective Bamboo is distributed worldwide, and its different parts are used as foods or as a traditional herb. Recently, antitumoral effects of bamboo extracts on several tumors have been increasingly reported; however, antitumoral activity of bamboo extracts on osteosarcoma remains unclear. In the present study, we investigated effects of an aqueous Phyllostachys edulis leaf extract (PEE) on osteosarcoma cells and the underlying mechanism of inhibition. Methods The growth of human osteosarcoma cell lines 143B and MG-63 and lung fibroblast MRC-5 cells was determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. Apoptosis was demonstrated using TUNEL (terminal deoxynucleotidyl transferase dUTP nick end labeling) assay and flow cytometric analysis. Phosphorylation and protein levels were determined by immunoblotting. Results After treatment with PEE, viability of 143B and MG-63 cells was dose-dependently reduced to 36.3%±1.6% of control values, which were similar to AICAR (5-aminoimidazole-4-carboxamide 1-β-D-ribofuranoside) treatments. In parallel, ratios of apoptotic cells and cells in the sub-G1 phase were significantly increased. Further investigation showed that PEE treatments led to activation of caspase cascades and changes of apoptotic mediators Bcl2, Bax, and p53. Consistently, our results revealed that PEE activated adenosine monophosphate-activated protein kinase (AMPK) signaling, and the AMPK activation was associated with the induction of apoptotic signaling. Conclusion Our results indicated that PEE suppressed the growth of 143B and MG-63 cells but moderately affected MRC-5 cells. PEE-induced apoptosis may attribute to AMPK activation and the following activation of apoptotic signaling cascades. These findings revealed that PEE possesses antitumoral activity on human osteosarcoma cells by manipulating AMPK signaling, suggesting that PEE alone or combined with regular antitumor drugs may be beneficial as osteosarcoma

  3. Pain management for chronic musculoskeletal conditions: the development of an evidence-based and theory-informed pain self-management course

    PubMed Central

    Carnes, Dawn; Homer, Kate; Underwood, Martin; Pincus, Tamar; Rahman, Anisur; Taylor, Stephanie J C

    2013-01-01

    Objective To devise and test a self-management course for chronic pain patients based on evidence and underpinned by theory using the Medical Research Council (MRC) framework for developing complex interventions. Design We used a mixed method approach. We conducted a systematic review of the effectiveness of components and characteristics of pain management courses. We then interviewed chronic pain patients who had attended pain and self-management courses. Behavioural change theories were mapped onto our findings and used to design the intervention. We then conducted a feasibility study to test the intervention. Setting Primary care in the inner city of London, UK. Participants Adults (18 years or older) with chronic musculoskeletal pain. Outcomes Related disability, quality of life, coping, depression, anxiety, social integration and healthcare resource use. Results The systematic reviews indicated that group-based courses with joint lay and healthcare professional leadership and that included a psychological component of short duration (<8 weeks) showed considerable promise. The qualitative research indicated that participants liked relaxation, valued social interaction and course location, and that timing and good tutoring were important determinants of attendance. We used behavioural change theories (social learning theory and cognitive behaviour approaches (CBA)) to inform course content. The course addressed: understanding and accepting pain, mood and pain, unhelpful thoughts and behaviour, problem solving, goal setting, action planning, movement, relaxation and social integration/reactivation. Attendance was 85%; we modified the recruitment of patients, the course and the training of facilitators as a result of testing. Conclusions The MRC guidelines were helpful in developing this intervention. It was possible to train both lay and non-psychologists to facilitate the courses and deliver CBA. The course was feasible and well received. PMID:24231458

  4. The planning, execution, and evaluation of a mass prophylaxis full-scale exercise in cook county, IL.

    PubMed

    Kilianski, Andy; O'Rourke, Amy T; Carlson, Crystal L; Parikh, Shannon M; Shipman-Amuwo, Frankie

    2014-01-01

    Increasing threats of bioterrorism and the emergence of novel disease agents, including the recent international outbreaks of H7N9 influenza and MERS-CoV, have stressed the importance and highlighted the need for public health preparedness at local, regional, and national levels. To test plans that were developed for mass prophylaxis scenarios, in April 2013 the Cook Country Department of Public Health (CCDPH) and the Triple Community (TripCom) Medical Reserve Corps (MRC) executed a full-scale mass prophylaxis exercise in response to a simulated anthrax bioterrorism attack. The exercise took place over 2 days and included the TripCom Point-of-Dispensing (POD) Management Team, volunteers from the TripCom MRC, and neighboring public health departments and MRCs. Individuals from the community volunteered as actors during the exercise, while local municipal, police, and fire personnel coordinated their responses to create the most realistic simulation possible. The exercise was designed to test the capacity of TripCom and CCDPH to implement plans for organizing municipal staff and volunteers to efficiently distribute prophylaxis to the community. Based on results from POD clinic flow, accuracy of prophylaxis distribution, and observations from evaluators, the exercise was successful in demonstrating areas that were operationally efficient as well as identifying areas that can be improved on. These include improvements to the just-in-time training for POD staff, the health screening and consent forms handed out to patients, the physical setup of the POD, and the command structure and communication for the management of POD operations. This article demonstrates the need for full-scale exercises and identifies gaps in POD planning that can be integrated into future plans, exercises, and emergency response.

  5. Exposure of rats to a high but not low dose of ethanol during early postnatal life increases the rate of loss of optic nerve axons and decreases the rate of myelination

    PubMed Central

    HARRIS, SIMON J.; WILCE, PETER; BEDI, KULDIP S.

    2000-01-01

    Visual system abnormalities are commonly encountered in the fetal alcohol syndrome although the level of exposure at which they become manifest is uncertain. In this study we have examined the effects of either low (ETLD) or high dose (ETHD) ethanol, given between postnatal days 4–9, on the axons of the rat optic nerve. Rats were exposed to ethanol vapour in a special chamber for a period of 3 h per day during the treatment period. The blood alcohol concentration in the ETLD animals averaged ∼ 171 mg/dl and in the ETHD animals ∼ 430 mg/dl at the end of the treatment on any given day. Groups of 10 and 30-d-old mother-reared control (MRC), separation control (SC), ETLD and ETHD rats were anaesthetised with an intraperitoneal injection of ketamine and xylazine, and killed by intracardiac perfusion with phosphate-buffered glutaraldehyde. In the 10-d-old rat optic nerves there was a total of ∼ 145000–165000 axons in MRC, SC and ETLD animals. About 4% of these fibres were myelinated. The differences between these groups were not statistically significant. However, the 10-d-old ETHD animals had only about 75000 optic nerve axons (P < 0.05) of which about 2.8% were myelinated. By 30 d of age there was a total of between 75000–90000 optic nerve axons, irrespective of the group examined. The proportion of axons which were myelinated at this age was still significantly lower (P < 0.001) in the ETHD animals (∼ 77%) than in the other groups (about 98%). It is concluded that the normal stages of development and maturation of the rat optic nerve axons, as assessed in this study, can be severely compromised by exposure to a relatively high (but not low) dose of ethanol between postnatal d 4 and 9. PMID:11117631

  6. New GOLD classification: longitudinal data on group assignment

    PubMed Central

    2014-01-01

    Rationale Little is known about the longitudinal changes associated with using the 2013 update of the multidimensional GOLD strategy for chronic obstructive pulmonary disease (COPD). Objective To determine the COPD patient distribution of the new GOLD proposal and evaluate how this classification changes over one year compared with the previous GOLD staging based on spirometry only. Methods We analyzed data from the CHAIN study, a multicenter observational Spanish cohort of COPD patients who are monitored annually. Categories were defined according to the proposed GOLD: FEV1%, mMRC dyspnea, COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ), and exacerbations-hospitalizations. One-year follow-up information was available for all variables except CCQ data. Results At baseline, 828 stable COPD patients were evaluated. On the basis of mMRC dyspnea versus CAT, the patients were distributed as follows: 38.2% vs. 27.2% in group A, 17.6% vs. 28.3% in group B, 15.8% vs. 12.9% in group C, and 28.4% vs. 31.6% in group D. Information was available for 526 patients at one year: 64.2% of patients remained in the same group but groups C and D show different degrees of variability. The annual progression by group was mainly associated with one-year changes in CAT scores (RR, 1.138; 95%CI: 1.074-1.206) and BODE index values (RR, 2.012; 95%CI: 1.487-2.722). Conclusions In the new GOLD grading classification, the type of tool used to determine the level of symptoms can substantially alter the group assignment. A change in category after one year was associated with longitudinal changes in the CAT and BODE index. PMID:24417879

  7. Modulation of Rho GTPases rescues brain mitochondrial dysfunction, cognitive deficits and aberrant synaptic plasticity in female mice modeling Rett syndrome.

    PubMed

    De Filippis, Bianca; Valenti, Daniela; Chiodi, Valentina; Ferrante, Antonella; de Bari, Lidia; Fiorentini, Carla; Domenici, Maria Rosaria; Ricceri, Laura; Vacca, Rosa Anna; Fabbri, Alessia; Laviola, Giovanni

    2015-06-01

    Rho GTPases are molecules critically involved in neuronal plasticity and cognition. We have previously reported that modulation of brain Rho GTPases by the bacterial toxin CNF1 rescues the neurobehavioral phenotype in MeCP2-308 male mice, a model of Rett syndrome (RTT). RTT is a rare X-linked neurodevelopmental disorder and a genetic cause of intellectual disability, for which no effective therapy is available. Mitochondrial dysfunction has been proposed to be involved in the mechanism of the disease pathogenesis. Here we demonstrate that modulation of Rho GTPases by CNF1 rescues the reduced mitochondrial ATP production via oxidative phosphorylation in the brain of MeCP2-308 heterozygous female mice, the condition which more closely recapitulates that of RTT patients. In RTT mouse brain, CNF1 also restores the alterations in the activity of the mitochondrial respiratory chain (MRC) complexes and of ATP synthase, the molecular machinery responsible for the majority of cell energy production. Such effects were achieved through the upregulation of the protein content of those MRC complexes subunits, which were defective in RTT mouse brain. Restored mitochondrial functionality was accompanied by the rescue of deficits in cognitive function (spatial reference memory in the Barnes maze), synaptic plasticity (long-term potentiation) and Tyr1472 phosphorylation of GluN2B, which was abnormally enhanced in the hippocampus of RTT mice. Present findings bring into light previously unknown functional mitochondrial alterations in the brain of female mice modeling RTT and provide the first evidence that RTT brain mitochondrial dysfunction can be rescued by modulation of Rho GTPases.

  8. Does a single plasma phenylalanine predict quality of control in phenylketonuria?

    PubMed Central

    MacDonald, A; Rylance, G; Asplin, D; Hall, S; Booth, I

    1998-01-01

    A 1993 MRC working group on phenylketonuria suggested standardising blood phenylalanine measurements by taking blood samples at the same time each day. Since it is not known how representative of a 24 hour period a single phenylalanine concentration is, the aim of this study was to investigate the 24 hour variability of plasma phenylalanine in well controlled children with phenylketonuria. Sixteen subjects, 12 girls and four boys aged 1 to 18 years, had hourly venous blood samples collected for 13 hours between 09.00and 21.00 on one day. Serial skin puncture blood specimens were then collected at 24.00, 03.00, and 06.00 within the same 24 hour period. All food and drink was weighed. The median variation in plasma phenylalanine concentration was 155 µmol/l/day, with a minimum of 80 and a maximum of 280. The highest concentration occurred in the morning between 6.00 and 9.00 in 63% of subjects; the lowest occurred between midday and midnight in 94%. Concentrations < 100 µmol/l occurred in 46% of children below 11 years, three having concentrations < 30 µmol/l for two, six, and seven hours respectively. Three of five subjects had concentrations above the MRC guidelines for 24% of the period studied. Except in two subjects, the blood concentrations did not rise in response to phenylalanine consumption. However, the greater the quantity of protein substitute taken between waking and the 16.00 specimen, the larger the decrease in daytime phenylalanine concentration (r = −0.7030) (p < 0.005). There is therefore wide variability in phenylalanine concentrations in a 24 hour period in children with phenylketonuria which is not reflected in a single observation. Further study is needed to investigate the effects of timing of protein substitute on the stability of phenylalanine concentrations.

 PMID:9579152

  9. Whole genome detection of rotavirus mixed infections in human, porcine and bovine samples co-infected with various rotavirus strains collected from sub-Saharan Africa.

    PubMed

    Nyaga, Martin M; Jere, Khuzwayo C; Esona, Mathew D; Seheri, Mapaseka L; Stucker, Karla M; Halpin, Rebecca A; Akopov, Asmik; Stockwell, Timothy B; Peenze, Ina; Diop, Amadou; Ndiaye, Kader; Boula, Angeline; Maphalala, Gugu; Berejena, Chipo; Mwenda, Jason M; Steele, A Duncan; Wentworth, David E; Mphahlele, M Jeffrey

    2015-04-01

    Group A rotaviruses (RVA) are among the main global causes of severe diarrhea in children under the age of 5years. Strain diversity, mixed infections and untypeable RVA strains are frequently reported in Africa. We analysed rotavirus-positive human stool samples (n=13) obtained from hospitalised children under the age of 5years who presented with acute gastroenteritis at sentinel hospital sites in six African countries, as well as bovine and porcine stool samples (n=1 each), to gain insights into rotavirus diversity and evolution. Polyacrylamide gel electrophoresis (PAGE) analysis and genotyping with G-(VP7) and P-specific (VP4) typing primers suggested that 13 of the 15 samples contained more than 11 segments and/or mixed G/P genotypes. Full-length amplicons for each segment were generated using RVA-specific primers and sequenced using the Ion Torrent and/or Illumina MiSeq next-generation sequencing platforms. Sequencing detected at least one segment in each sample for which duplicate sequences, often having distinct genotypes, existed. This supported and extended the PAGE and RT-PCR genotyping findings that suggested these samples were collected from individuals that had mixed rotavirus infections. The study reports the first porcine (MRC-DPRU1567) and bovine (MRC-DPRU3010) mixed infections. We also report a unique genome segment 9 (VP7), whose G9 genotype belongs to lineage VI and clusters with porcine reference strains. Previously, African G9 strains have all been in lineage III. Furthermore, additional RVA segments isolated from humans have a clear evolutionary relationship with porcine, bovine and ovine rotavirus sequences, indicating relatively recent interspecies transmission and reassortment. Thus, multiple RVA strains from sub-Saharan Africa are infecting mammalian hosts with unpredictable variations in their gene segment combinations. Whole-genome sequence analyses of mixed RVA strains underscore the considerable diversity of rotavirus sequences and

  10. Magneto-resistive coefficient enhancement observed around Verwey-like transition on spinel ferrites XFe{sub 2}O{sub 4} (X = Mn, Zn)

    SciTech Connect

    López Maldonado, K. L. Vazquez Zubiate, L.; Elizalde Galindo, J. T.; Presa, P. de la; Matutes Aquino, J. A.

    2014-05-07

    Manganese and Zinc ferrites were prepared by solid state reaction. The resulting powders were pressed into pellets and heat treated at 1100 °C. The samples were characterized by using X-ray diffraction, pure phases of zinc ferrite (ZnFe{sub 2}O{sub 4}) and manganese ferrite (MnFe{sub 2}O{sub 4}) were obtained. Scanning electron microscopy images showed a good contact between particles. A drop of electrical resistance was found in both samples, MnFe{sub 2}O{sub 4} and ZnFe{sub 2}O{sub 4}, with values going from 2750 to 130 Ω and from 1100 to 55 Ω, respectively. Transition temperatures were determined to be T{sub V} = 225 K for MnFe{sub 2}O{sub 4} and T{sub V} = 130 K for ZnFe{sub 2}O{sub 4}. Magnetoresistance measurements were carried out in the temperature range where R showed the transition, defined as the Verwey-like transition temperature range, ΔT{sub V}. No magnetoresistive effect was observed out of it. The magnetoresistive coefficient (MRC) observed at ΔT{sub V} reached its maximum values of 1.1% for MnFe{sub 2}O{sub 4} and 6.68% for ZnFe{sub 2}O{sub 4}. The differences between MRC values are related to the divalent metal element used. Finally, the magnetoresistive response indicates that the electrical transition observed is strongly influencing the magnetoresistance; where the underlying responsible for this behavior could be a charge reordering occurring at the Verwey-like transition temperature.

  11. Whole genome detection of rotavirus mixed infections in human, porcine and bovine samples co-infected with various rotavirus strains collected from sub-Saharan Africa

    PubMed Central

    Nyaga, Martin M.; Jere, Khuzwayo C.; Esona, Mathew D.; Seheri, Mapaseka L.; Stucker, Karla M.; Halpin, Rebecca A.; Akopov, Asmik; Stockwell, Timothy B.; Peenze, Ina; Diop, Amadou; Ndiaye, Kader; Boula, Angeline; Maphalala, Gugu; Berejena, Chipo; Mwenda, Jason M.; Steele, A. Duncan; Wentworth, David E.; Mphahlele, M. Jeffrey

    2015-01-01

    Group A rotaviruses (RVA) are among the main global causes of severe diarrhea in children under the age of 5 years. Strain diversity, mixed infections and untypeable RVA strains are frequently reported in Africa. We analysed rotavirus-positive human stool samples (n=13) obtained from hospitalised children under the age of 5 years who presented with acute gastroenteritis at sentinel hospital sites in six African countries, as well as bovine and porcine stool samples (n=1 each), to gain insights into rotavirus diversity and evolution. Polyacrylamide gel electrophoresis (PAGE) analysis and genotyping with G- (VP7) and P-specific (VP4) typing primers suggested that 13 of the 15 samples contained more than 11 segments and/or mixed G/P genotypes. Full-length amplicons for each segment were generated using RVA-specific primers and sequenced using the Ion Torrent and/or Illumina MiSeq next-generation sequencing platforms. Sequencing detected at least one segment in each sample for which duplicate sequences, often having distinct genotypes, existed. This supported and extended the PAGE and RT-PCR genotyping findings that suggested these samples were collected from individuals that had mixed rotavirus infections. The study reports the first porcine (MRC-DPRU1567) and bovine (MRC-DPRU3010) mixed infections. We also report a unique genome segment 9 (VP7), whose G9 genotype belongs to lineage VI and clusters with porcine reference strains. Previously, African G9 strains have all been in lineage III. Furthermore, additional RVA segments isolated from humans have a clear evolutionary relationship with porcine, bovine and ovine rotavirus sequences, indicating relatively recent interspecies transmission and reassortment. Thus, multiple RVA strains from sub-Saharan Africa are infecting mammalian hosts with unpredictable variations in their gene segment combinations. Whole-genome sequence analyses of mixed RVA strains underscore the considerable diversity of rotavirus sequences and

  12. Recovery of hand function with robot-assisted therapy in acute stroke patients: a randomized-controlled trial.

    PubMed

    Sale, Patrizio; Mazzoleni, Stefano; Lombardi, Valentina; Galafate, Daniele; Massimiani, Maria P; Posteraro, Federico; Damiani, Carlo; Franceschini, Marco

    2014-09-01

    In the last few years, not many studies on the use of robot-assisted therapy to recover hand function in acute stroke patients have been carried out. This randomized-controlled observer trial is aimed at evaluating the effects of intensive robot-assisted hand therapy compared with intensive occupational therapy in the early recovery phases after stroke with a 3-month follow-up. Twenty acute stroke patients at their first-ever stroke were enrolled and randomized into two groups. The experimental treatment was performed using the Amadeo Robotic System. Control treatment, instead, was carried out using occupational therapy executed by a trained physiotherapist. All participants received 20 sessions of treatment for 4 consecutive weeks (5 days/week). The following clinical scales, Fugl-Meyer Scale (FM), Medical Research Council Scale for Muscle Strength (hand flexor and extensor muscles) (MRC), Motricity Index (MI) and modified Ashworth Scale for wrist and hand muscles (MAS), were performed at baseline (T0), after 20 sessions (end of treatment) (T1) and at the 3-month follow-up (T2). The Barthel Index was assessed only at T0 and T1. Evidence of a significant improvement was shown by the Friedman test for the FM [experimental group (EG): P=0.0039, control group (CG): P<0.0001], Box and Block Test (EG: P=0.0185, CG: P=0.0086), MI (EG: P<0.0001, CG: P=0.0303) and MRC (EG: P<0.0001, CG: P=0.001) scales. These results provide further support to the generalized therapeutic impact of intensive robot-assisted treatment on hand recovery functions in individuals with acute stroke. The robotic rehabilitation treatment may contribute toward the recovery of hand motor function in acute stroke patients. The positive results obtained through the safe and reliable robotic rehabilitation treatment reinforce the recommendation to extend it to a larger clinical practice.

  13. Administration of CoQ10 analogue ameliorates dysfunction of the mitochondrial respiratory chain in a mouse model of Angelman syndrome.

    PubMed

    Llewellyn, Katrina J; Nalbandian, Angèle; Gomez, Arianna; Wei, Don; Walker, Naomi; Kimonis, Virginia E

    2015-04-01

    Genetic defects in the UBE3A gene, which encodes for the imprinted E6-AP ubiquitin E3 ligase (UBE3A), is responsible for the occurrence of Angelman syndrome (AS), a neurodegenerative disorder which arises in 1 out of every 12,000-20,000 births. Classical symptoms of AS include delayed development, impaired speech, and epileptic seizures with characteristic electroencephalography (EEG) readings. We have previously reported impaired mitochondrial structure and reduced complex III in the hippocampus and cerebellum in the Ube3a(m-/p+) mice. CoQ10 supplementation restores the electron flow to the mitochondrial respiratory chain (MRC) to ultimately increase mitochondrial antioxidant capacity. A number of recent studies with CoQ10 analogues seem promising in providing therapeutic benefit to patients with a variety of disorders. CoQ10 therapy has been reported to be safe and relatively well-tolerated at doses as high as 3000mg/day in patients with disorders of CoQ10 biosynthesis and MRC disorders. Herein, we report administration of idebenone, a potent CoQ10 analogue, to the Ube3a(m-/p+) mouse model corrects motor coordination and anxiety levels, and also improves the expression of complexes III and IV in hippocampus CA1 and CA2 neurons and cerebellum in these Ube3a(m-/p+) mice. However, treatment with idebenone illustrated no beneficial effects in the reduction of oxidative stress. To our knowledge, this is the first study to suggest an improvement in mitochondrial respiratory chain dysfunction via bioenergetics modulation with a CoQ10 analogue. These findings may further elucidate possible cellular and molecular mechanism(s) and ultimately a clinical therapeutic approach/benefit for patients with Angelman syndrome. PMID:25684537

  14. Triangle orientation discrimination: the alternative to minimum resolvable temperature difference and minimum resolvable contrast

    NASA Astrophysics Data System (ADS)

    Bijl, Piet; Valeton, J. Mathieu

    1998-07-01

    The characterization of electro-optical system performance by means of the minimum resolvable temperature difference (MRTD) or the minimum resolvable contrast (MRC) has at least three serious disadvantages: (1) the bar pattern stimulus is theoretically and practically unsuitable for 1D or 2D spatially sampled systems such as pixel-array cameras, (2) spatial phase is not taken into account, and (3) the results depend on the observer's subjective decision criterion. We propose an adequate and easily applicable alternative: the triangle orientation discrimination (TOD) threshold. The TOD is based on an improved test pattern, a better defined observer task, and a solid psychophysical measurement procedure. The method has a large number of theoretical and practical advantages: it is suitable for pixel-array cameras, scanning systems and other electro-optical and optical imaging system sin both the thermal and visual domains, it has a close relationship to real target acquisition, and the observer task is easy. The results are free from observer bias and allow statistical significance tests. The method lends itself very well to automatic measurements, and can be extended for future sensor systems that include advanced image processing. The TOD curve can be implemented easily in a target acquisition (TA) model such as ACQUIRE. An observer performance study with real targets shows that the TOD curve better predicts TA performance than the mRC does. The method has been implemented successfully in a thermal imager field test apparatus called the thermal imager performance indicator and may be implemented in current MRTD test equipment with little effort.

  15. BioAfrica's HIV-1 proteomics resource: combining protein data with bioinformatics tools.

    PubMed

    Doherty, Ryan S; De Oliveira, Tulio; Seebregts, Chris; Danaviah, Sivapragashini; Gordon, Michelle; Cassol, Sharon

    2005-01-01

    Most Internet online resources for investigating HIV biology contain either bioinformatics tools, protein information or sequence data. The objective of this study was to develop a comprehensive online proteomics resource that integrates bioinformatics with the latest information on HIV-1 protein structure, gene expression, post-transcriptional/post-translational modification, functional activity, and protein-macromolecule interactions. The BioAfrica HIV-1 Proteomics Resource http://bioafrica.mrc.ac.za/proteomics/index.html is a website that contains detailed information about the HIV-1 proteome and protease cleavage sites, as well as data-mining tools that can be used to manipulate and query protein sequence data, a BLAST tool for initiating structural analyses of HIV-1 proteins, and a proteomics tools directory. The Proteome section contains extensive data on each of 19 HIV-1 proteins, including their functional properties, a sample analysis of HIV-1HXB2, structural models and links to other online resources. The HIV-1 Protease Cleavage Sites section provides information on the position, subtype variation and genetic evolution of Gag, Gag-Pol and Nef cleavage sites. The HIV-1 Protein Data-mining Tool includes a set of 27 group M (subtypes A through K) reference sequences that can be used to assess the influence of genetic variation on immunological and functional domains of the protein. The BLAST Structure Tool identifies proteins with similar, experimentally determined topologies, and the Tools Directory provides a categorized list of websites and relevant software programs. This combined database and software repository is designed to facilitate the capture, retrieval and analysis of HIV-1 protein data, and to convert it into clinically useful information relating to the pathogenesis, transmission and therapeutic response of different HIV-1 variants. The HIV-1 Proteomics Resource is readily accessible through the BioAfrica website at: http://bioafrica.mrc

  16. The Toll-Like Receptor 5 Agonist Entolimod Mitigates Lethal Acute Radiation Syndrome in Non-Human Primates.

    PubMed

    Krivokrysenko, Vadim I; Toshkov, Ilia A; Gleiberman, Anatoli S; Krasnov, Peter; Shyshynova, Inna; Bespalov, Ivan; Maitra, Ratan K; Narizhneva, Natalya V; Singh, Vijay K; Whitnall, Mark H; Purmal, Andrei A; Shakhov, Alexander N; Gudkov, Andrei V; Feinstein, Elena

    2015-01-01

    There are currently no approved medical radiation countermeasures (MRC) to reduce the lethality of high-dose total body ionizing irradiation expected in nuclear emergencies. An ideal MRC would be effective even when administered well after radiation exposure and would counteract the effects of irradiation on the hematopoietic system and gastrointestinal tract that contribute to its lethality. Entolimod is a Toll-like receptor 5 agonist with demonstrated radioprotective/mitigative activity in rodents and radioprotective activity in non-human primates. Here, we report data from several exploratory studies conducted in lethally irradiated non-human primates (rhesus macaques) treated with a single intramuscular injection of entolimod (in the absence of intensive individualized supportive care) administered in a mitigative regimen, 1-48 hours after irradiation. Following exposure to LD50-70/40 of radiation, injection of efficacious doses of entolimod administered as late as 25 hours thereafter reduced the risk of mortality 2-3-fold, providing a statistically significant (P<0.01) absolute survival advantage of 40-60% compared to vehicle treatment. Similar magnitude of survival improvement was also achieved with drug delivered 48 hours after irradiation. Improved survival was accompanied by predominantly significant (P<0.05) effects of entolimod administration on accelerated morphological recovery of hematopoietic and immune system organs, decreased severity and duration of thrombocytopenia, anemia and neutropenia, and increased clonogenic potential of the bone marrow compared to control irradiated animals. Entolimod treatment also led to reduced apoptosis and accelerated crypt regeneration in the gastrointestinal tract. Together, these data indicate that entolimod is a highly promising potential life-saving treatment for victims of radiation disasters. PMID:26367124

  17. Cellular requirements for renal allograft rejection in the athymic nude rat

    PubMed Central

    1989-01-01

    This study has examined the ability of adoptively transferred CD4+ and CD8+ T cells to mediate rejection of a fully allogeneic DA renal graft in the PVG nude rat. Transfer, at the time of transplantation, of naive CD4+ T cells caused rapid graft rejection and primed CD4+ cells were several times more potent. In contrast, naive or specifically sensitized CD8+ cells were entirely ineffective at mediating renal allograft rejection. Whereas nonrejecting grafts showed only a mild cellular infiltrate, rejecting grafts in CD4+ reconstituted animals showed a substantial infiltrate and many of the infiltrating cells had a phenotype (MRC OX8+, MRC OX19-), consistent with NK cells. Experiments using a mAb (HIS 41) against an allotypic determinant of the leukocyte common antigen confirmed that the majority (greater than 80%) of the cellular infiltrate in rejecting grafts derived from the host rather than from the CD4+ inoculum. Infiltrating mononuclear cells, obtained from rejecting allografts 7 d after transplantation in CD4+-injected PVG nude hosts, showed high levels of in vitro cytotoxicity against not only kidney donor strain Con A blasts but also third-party allogeneic Con A blasts, as well as against both NK and LAK susceptible targets. When splenocytes from nontransplanted nude PVG rats were tested in vitro they also demonstrated high levels of lytic activity against both NK and LAK susceptible targets as well as allogeneic Con A blasts, which were not susceptible to lysis by spleen cells from euthymic rats. These findings suggest that injected CD4+ cells may cause renal allograft rejection by the recruitment of extrathymically derived, widely alloreactive cells into the kidney in this model of graft rejection. PMID:2659723

  18. CRISPLD2 (LGL1) inhibits proinflammatory mediators in human fetal, adult, and COPD lung fibroblasts and epithelial cells.

    PubMed

    Zhang, Hui; Kho, Alvin T; Wu, Qing; Halayko, Andrew J; Limbert Rempel, Karen; Chase, Robert P; Sweezey, Neil B; Weiss, Scott T; Kaplan, Feige

    2016-09-01

    Chronic lung disease of prematurity/bronchopulmonary dysplasia (BPD) is the leading cause of perinatal morbidity in developed countries. Inflammation is a prominent finding. Currently available interventions have associated toxicities and limited efficacy. While BPD often resolves in childhood, survivors of preterm birth are at risk for acquired respiratory disease in early life and are more likely to develop chronic obstructive pulmonary disease (COPD) in adulthood. We previously cloned Crispld2 (Lgl1), a glucocorticoid-regulated mesenchymal secretory protein that modulates lung branching and alveogenesis through mesenchymal-epithelial interactions. Absence of Crispld2 is embryonic lethal. Heterozygous Crispld2+/- mice display features of BPD, including distal airspace enlargement, disruption of elastin, and neonatal lung inflammation. CRISPLD2 also plays a role in human fetal lung fibroblast cell expansion, migration, and mesenchymal-epithelial signaling. This study assessed the effects of endogenous and exogenous CRISPLD2 on expression of proinflammatory mediators in human fetal and adult (normal and COPD) lung fibroblasts and epithelial cells. CRISPLD2 expression was upregulated in a lipopolysaccharide (LPS)-induced human fetal lung fibroblast line (MRC5). LPS-induced upregulation of the proinflammatory cytokines IL-8 and CCL2 was exacerbated in MRC5-CRISPLD2(knockdown) cells. siRNA suppression of endogenous CRISPLD2 in adult lung fibroblasts (HLFs) led to augmented expression of IL-8, IL-6, CCL2. LPS-stimulated expression of proinflammatory mediators by human lung epithelial HAEo- cells was attenuated by purified secretory CRISPLD2. RNA sequencing results from HLF-CRISPLD2(knockdown) suggest roles for CRISPLD2 in extracellular matrix and in inflammation. Our data suggest that suppression of CRISPLD2 increases the risk of lung inflammation in early life and adulthood. PMID:27597766

  19. Long-term results of diaphragmatic plication in adults with unilateral diaphragm paralysis

    PubMed Central

    2010-01-01

    Background In this study we aimed to evaluate the long-term outcome of diaphragmatic plication for symptomatic unilateral diaphragm paralysis. Methods Thirteen patients who underwent unilateral diaphragmatic plication (2 patients had right, 11 left plication) between January 2003 and December 2006 were evaluated. One patient died postoperatively due to sepsis. The remaining 12 patients [9 males, 3 females; mean age 60 (36-66) years] were reevaluated with chest radiography, flouroscopy or ultrasonography, pulmonary function tests, computed tomography (CT) or magnetic resonance imaging (MRI), and the MRC/ATS dyspnea score at an average of 5.4 (4-7) years after diaphragmatic plication. Results The etiology of paralysis was trauma (9 patients), cardiac by pass surgery (3 patients), and idiopathic (1 patient). The principle symptom was progressive dyspnea with a mean duration of 32.9 (22-60) months before surgery. All patients had an elevated hemidiaphragm and paradoxical movement radiologically prior to surgery. There were partial atelectasis and reccurent infection of the lower lobe in the affected side on CT in 9 patients. Atelectasis was completely improved in 9 patients after plication. Preoperative spirometry showed a clear restrictive pattern. Mean preoperative FVC was 56.7 ± 11.6% and FEV1 65.3 ± 8.7%. FVC and FEV1 improved by 43.6 ± 30.6% (p < 0.001) and 27.3 ± 10.9% (p < 0.001) at late follow-up. MRC/ATS dyspnea scores improved 3 points in 11 patients and 1 point in 1 patient at long-term (p < 0.0001). Eight patients had returned to work at 3 months after surgery. Conclusions Diaphragmatic plication for unilateral diaphragm paralysis decreases lung compression, ensures remission of symptoms, and improves quality of life in long-term period. PMID:21078140

  20. Comparative analyses of gene copy number and mRNA expression in GBM tumors and GBM xenografts

    SciTech Connect

    Hodgson, J. Graeme; Yeh, Ru-Fang; Ray, Amrita; Wang, Nicholas J.; Smirnov, Ivan; Yu, Mamie; Hariono, Sujatmi; Silber, Joachim; Feiler, Heidi S.; Gray, Joe W.; Spellman, Paul T.; Vandenberg, Scott R.; Berger, Mitchel S.; James, C. David

    2009-04-03

    Development of model systems that recapitulate the molecular heterogeneity observed among glioblastoma multiforme (GBM) tumors will expedite the testing of targeted molecular therapeutic strategies for GBM treatment. In this study, we profiled DNA copy number and mRNA expression in 21 independent GBM tumor lines maintained as subcutaneous xenografts (GBMX), and compared GBMX molecular signatures to those observed in GBM clinical specimens derived from the Cancer Genome Atlas (TCGA). The predominant copy number signature in both tumor groups was defined by chromosome-7 gain/chromosome-10 loss, a poor-prognosis genetic signature. We also observed, at frequencies similar to that detected in TCGA GBM tumors, genomic amplification and overexpression of known GBM oncogenes, such as EGFR, MDM2, CDK6, and MYCN, and novel genes, including NUP107, SLC35E3, MMP1, MMP13, and DDX1. The transcriptional signature of GBMX tumors, which was stable over multiple subcutaneous passages, was defined by overexpression of genes involved in M phase, DNA replication, and chromosome organization (MRC) and was highly similar to the poor-prognosis mitosis and cell-cycle module (MCM) in GBM. Assessment of gene expression in TCGA-derived GBMs revealed overexpression of MRC cancer genes AURKB, BIRC5, CCNB1, CCNB2, CDC2, CDK2, and FOXM1, which form a transcriptional network important for G2/M progression and/or checkpoint activation. Our study supports propagation of GBM tumors as subcutaneous xenografts as a useful approach for sustaining key molecular characteristics of patient tumors, and highlights therapeutic opportunities conferred by this GBMX tumor panel for testing targeted therapeutic strategies for GBM treatment.

  1. MT-HESS: an efficient Bayesian approach for simultaneous association detection in OMICS datasets, with application to eQTL mapping in multiple tissues

    PubMed Central

    Lewin, Alex; Saadi, Habib; Peters, James E.; Moreno-Moral, Aida; Lee, James C.; Smith, Kenneth G. C.; Petretto, Enrico; Bottolo, Leonardo; Richardson, Sylvia

    2016-01-01

    Motivation: Analysing the joint association between a large set of responses and predictors is a fundamental statistical task in integrative genomics, exemplified by numerous expression Quantitative Trait Loci (eQTL) studies. Of particular interest are the so-called ‘hotspots’, important genetic variants that regulate the expression of many genes. Recently, attention has focussed on whether eQTLs are common to several tissues, cell-types or, more generally, conditions or whether they are specific to a particular condition. Results: We have implemented MT-HESS, a Bayesian hierarchical model that analyses the association between a large set of predictors, e.g. SNPs, and many responses, e.g. gene expression, in multiple tissues, cells or conditions. Our Bayesian sparse regression algorithm goes beyond ‘one-at-a-time’ association tests between SNPs and responses and uses a fully multivariate model search across all linear combinations of SNPs, coupled with a model of the correlation between condition/tissue-specific responses. In addition, we use a hierarchical structure to leverage shared information across different genes, thus improving the detection of hotspots. We show the increase of power resulting from our new approach in an extensive simulation study. Our analysis of two case studies highlights new hotspots that would remain undetected by standard approaches and shows how greater prediction power can be achieved when several tissues are jointly considered. Availability and implementation: C++ source code and documentation including compilation instructions are available under GNU licence at http://www.mrc-bsu.cam.ac.uk/software/. Contact: sylvia.richardson@mrc-bsu.cam.ac.uk or lb664@cam.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26504141

  2. Gastric cancer: Current status of lymph node dissection

    PubMed Central

    Degiuli, Maurizio; De Manzoni, Giovanni; Di Leo, Alberto; D’Ugo, Domenico; Galasso, Erica; Marrelli, Daniele; Petrioli, Roberto; Polom, Karol; Roviello, Franco; Santullo, Francesco; Morino, Mario

    2016-01-01

    D2 procedure has been accepted in Far East as the standard treatment for both early (EGC) and advanced gastric cancer (AGC) for many decades. Recently EGC has been successfully treated with endoscopy by endoscopic mucosal resection or endoscopic submucosal dissection, when restricted or extended Gotoda's criteria can be applied and D1+ surgery is offered only to patients not fitted for less invasive treatment. Furthermore, two randomised controlled trials (RCTs) have been demonstrating the non inferiority of minimally invasive technique as compared to standard open surgery for the treatment of early cases and recently the feasibility of adequate D1+ dissection has been demonstrated also for the robot assisted technique. In case of AGC the debate on the extent of nodal dissection has been open for many decades. While D2 gastrectomy was performed as the standard procedure in eastern countries, mostly based on observational and retrospective studies, in the west the Medical Research Council (MRC), Dutch and Italian RCTs have been conducted to show a survival benefit of D2 over D1 with evidence based medicine. Unfortunately both the MRC and the Dutch trials failed to show a survival benefit after the D2 procedure, mostly due to the significant increase of postoperative morbidity and mortality, which was referred to splenopancreatectomy. Only 15 years after the conclusion of its accrual, the Dutch trial could report a significant decrease of recurrence after D2 procedure. Recently the long term survival analysis of the Italian RCT could demonstrate a benefit for patients with positive nodes treated with D2 gastrectomy without splenopancreatectomy. As nowadays also in western countries D2 procedure can be done safely with pancreas preserving technique and without preventive splenectomy, it has been suggested in several national guidelines as the recommended procedure for patients with AGC. PMID:26973384

  3. The planning, execution, and evaluation of a mass prophylaxis full-scale exercise in cook county, IL.

    PubMed

    Kilianski, Andy; O'Rourke, Amy T; Carlson, Crystal L; Parikh, Shannon M; Shipman-Amuwo, Frankie

    2014-01-01

    Increasing threats of bioterrorism and the emergence of novel disease agents, including the recent international outbreaks of H7N9 influenza and MERS-CoV, have stressed the importance and highlighted the need for public health preparedness at local, regional, and national levels. To test plans that were developed for mass prophylaxis scenarios, in April 2013 the Cook Country Department of Public Health (CCDPH) and the Triple Community (TripCom) Medical Reserve Corps (MRC) executed a full-scale mass prophylaxis exercise in response to a simulated anthrax bioterrorism attack. The exercise took place over 2 days and included the TripCom Point-of-Dispensing (POD) Management Team, volunteers from the TripCom MRC, and neighboring public health departments and MRCs. Individuals from the community volunteered as actors during the exercise, while local municipal, police, and fire personnel coordinated their responses to create the most realistic simulation possible. The exercise was designed to test the capacity of TripCom and CCDPH to implement plans for organizing municipal staff and volunteers to efficiently distribute prophylaxis to the community. Based on results from POD clinic flow, accuracy of prophylaxis distribution, and observations from evaluators, the exercise was successful in demonstrating areas that were operationally efficient as well as identifying areas that can be improved on. These include improvements to the just-in-time training for POD staff, the health screening and consent forms handed out to patients, the physical setup of the POD, and the command structure and communication for the management of POD operations. This article demonstrates the need for full-scale exercises and identifies gaps in POD planning that can be integrated into future plans, exercises, and emergency response. PMID:24697783

  4. Whole genome detection of rotavirus mixed infections in human, porcine and bovine samples co-infected with various rotavirus strains collected from sub-Saharan Africa.

    PubMed

    Nyaga, Martin M; Jere, Khuzwayo C; Esona, Mathew D; Seheri, Mapaseka L; Stucker, Karla M; Halpin, Rebecca A; Akopov, Asmik; Stockwell, Timothy B; Peenze, Ina; Diop, Amadou; Ndiaye, Kader; Boula, Angeline; Maphalala, Gugu; Berejena, Chipo; Mwenda, Jason M; Steele, A Duncan; Wentworth, David E; Mphahlele, M Jeffrey

    2015-04-01

    Group A rotaviruses (RVA) are among the main global causes of severe diarrhea in children under the age of 5years. Strain diversity, mixed infections and untypeable RVA strains are frequently reported in Africa. We analysed rotavirus-positive human stool samples (n=13) obtained from hospitalised children under the age of 5years who presented with acute gastroenteritis at sentinel hospital sites in six African countries, as well as bovine and porcine stool samples (n=1 each), to gain insights into rotavirus diversity and evolution. Polyacrylamide gel electrophoresis (PAGE) analysis and genotyping with G-(VP7) and P-specific (VP4) typing primers suggested that 13 of the 15 samples contained more than 11 segments and/or mixed G/P genotypes. Full-length amplicons for each segment were generated using RVA-specific primers and sequenced using the Ion Torrent and/or Illumina MiSeq next-generation sequencing platforms. Sequencing detected at least one segment in each sample for which duplicate sequences, often having distinct genotypes, existed. This supported and extended the PAGE and RT-PCR genotyping findings that suggested these samples were collected from individuals that had mixed rotavirus infections. The study reports the first porcine (MRC-DPRU1567) and bovine (MRC-DPRU3010) mixed infections. We also report a unique genome segment 9 (VP7), whose G9 genotype belongs to lineage VI and clusters with porcine reference strains. Previously, African G9 strains have all been in lineage III. Furthermore, additional RVA segments isolated from humans have a clear evolutionary relationship with porcine, bovine and ovine rotavirus sequences, indicating relatively recent interspecies transmission and reassortment. Thus, multiple RVA strains from sub-Saharan Africa are infecting mammalian hosts with unpredictable variations in their gene segment combinations. Whole-genome sequence analyses of mixed RVA strains underscore the considerable diversity of rotavirus sequences and

  5. Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

    SciTech Connect

    Miki, Takanori; Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo; Kusaka, Takashi; Warita, Katsuhiko; Yokoyama, Toshifumi; Jamal, Mostofa; Ueki, Masaaki; Yakura, Tomiko; Tamai, Motoki; Sumitani, Kazunori; Hosomi, Naohisa; Takeuchi, Yoshiki

    2013-12-06

    Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.

  6. [Metabolic intolerance to exercise].

    PubMed

    Arenas, J; Martín, M A

    2003-01-01

    Exercise intolerance (EI) is a frequent cause of medical attention, although it is sometimes difficult to come to a final diagnosis. However, there is a group of patients in whom EI is due to a metabolic dysfunction. McArdle's disease (type V glucogenosis) is due to myophosphorylase (MPL) deficiency. The ischemic exercise test shows a flat lactate curve. The most frequent mutations in the PYGM gene (MPL gene) in Spanish patients with MPL deficiency are R49X and W797R. Carnitine palmitoyltransferase (CPT) II deficiency is invariably associated to repetitive episodes of myoglobinuria triggered by exercise, cold, fever or fasting. The diagnosis depends on the demonstration of CPT II deficiency in muscle. The most frequent mutation in the CPT2 gene is the S113L. Patients with muscle adenylate deaminase deficiency usually show either a mild myopathy or no symptom. The diagnosis is based on the absence of enzyme activity in muscle and the lack of rise of ammonia in the forearm ischemic exercise test. The mutation Q12X in the AMPD1 gene is strongly associated with the disease. Exercise intolerance is a common complaint in patients with mitochondrial respiratory chain (MRC) deficiencies, although it is often overshadowed by other symptoms and signs. Only recently we have come to appreciate that exercise intolerance can be the sole presentation of defects in the mtDNA, particularly in complex I, complex III, complex IV, or in some tRNAs. In addition, myoglobinuria can be observed in patients under statin treatment, particularly if associated with fibrates, due to an alteration in the assembly of the complex IV of the MRC. PMID:12838448

  7. Long-term whole-body vibration training in two late-onset Pompe disease patients.

    PubMed

    Montagnese, Federica; Thiele, Simone; Wenninger, Stephan; Schoser, Benedikt

    2016-08-01

    The treatment of late-onset Pompe disease (LOPD) relies on enzyme replacement therapy (ERT) and physiotherapy but the most appropriate exercise program is not yet established. Whole-body vibration training (WBVT) has showed promising results, improving motor performances in various populations. Our aim is to assess the effects of WBVT performed by two LOPD patients in addition to ERT and physiotherapy. A side-alternating WBVT lasting 2 years; clinical assessments included: manual muscle testing (MRC sumscore), knee extension and arm flection isometric strength (multi-muscle tester M3diagnos), timed function tests (10 m walking, standing-up from chair, ascending 4-steps), 6 min walking (6 MWT), motor disability (Walton Gardner-Medwin scale), pulmonary function. Follow-up evaluations performed for 9 years since ERT start (pre-WBVT and post-WBVT) are reported for comparison. MRC sumscore improved in both patients (Pt.1:41 → 48, Pt.2:42 → 47) as isometric strength of knee extension (Pt.1: + 62 %, Pt.2: + 26 %) and arm flection (Pt.1: + 88 %, Pt.2: + 66 %), 6 MWT improved in Pt.1 (+75 m). Timed function tests did not greatly change. Patients reported no significant CK elevation or WBVT-related complaints. WBVT may be safely used in LOPD and seems to moderately boost muscle strength in patients receiving ERT and physiotherapy for more than 3 years. Larger cohorts should be studied to better assess WBVT potential as adjunctive exercise tool in LOPD. PMID:27193587

  8. Recent research in DNA repair, mutation and recombination: a report of the DNA Repair Network meeting, held at City University, London on 18 December 1995.

    PubMed

    Jones, N J; Strike, P

    1996-09-01

    The now traditional one day Christmas DNA Repair meeting was held at City University, London for the third year in succession. With over 130 participants and a programme consisting of a total of 24 pre-offered presentations the meeting reached record dimensions. Attendees were from 24 institutions throughout the United Kingdom, and with several distinct research groups contained within the large contingents from the ICRF Clare Hall Laboratories and the MRC Cell Mutation Unit in Brighton, this indicates the increasing interest and depth of UK research in DNA repair. One slight disappointment of the meeting was the fall in the numbers of non-UK participants. Although the meeting in 1994 (Strike, 1995) saw an increase in presentations from Continental Europe (six countries including France, Germany. The Netherlands and Switzerland), the trend did not continue this year, with only Denmark being represented. The 24 contributors consisted of approximately equal numbers of postgraduate students, postdoctoral researchers and more "established' scientists reflecting the continuing policy of encouraging younger members of the repair community to present their work. The mix of presenters was particularly well illustrated by two excellent and consecutive talks by Professor Bryn Bridges (MRC Cell Mutation Unit) and Alison Mitchell, a postgraduate student in Stephen West's laboratory (ICRF, Clare Hall). The organisms under study were as equally disparate and included Archaebacteria, Escherichia coli. Saccharomyces cerevisiae, Schizosaccharomyces pombe, Aspergillus, mice and men. The range of topics was also varied and included bacterial mutagenesis, NMR studies of Ada protein, preferential DNA repair, cell cycle checkpoint genes, reconstitution of nucleotide excision repair and V(D)J recombination in vitro, creation of repair deficient transgenic mice and mismatch defects in human cells. The result was a very successful meeting which was characterized by the consistently high

  9. Gulf of Mexico Regional Collaborative Final Report

    SciTech Connect

    Judd, Kathleen S.; Judd, Chaeli; Engel-Cox, Jill A.; Gulbransen, Thomas; Anderson, Michael G.; Woodruff, Dana L.; Thom, Ronald M.; Guzy, Michael; Hardin, Danny; Estes, Maury

    2007-12-01

    This report presents the results of the Gulf of Mexico Regional Collaborative (GoMRC), a year-long project funded by NASA. The GoMRC project was organized around end user outreach activities, a science applications team, and a team for information technology (IT) development. Key outcomes are summarized below for each of these areas. End User Outreach; Successfully engaged federal and state end users in project planning and feedback; With end user input, defined needs and system functional requirements; Conducted demonstration to End User Advisory Committee on July 9, 2007 and presented at Gulf of Mexico Alliance (GOMA) meeting of Habitat Identification committee; Conducted significant engagement of other end user groups, such as the National Estuary Programs (NEP), in the Fall of 2007; Established partnership with SERVIR and Harmful Algal Blooms Observing System (HABSOS) programs and initiated plan to extend HABs monitoring and prediction capabilities to the southern Gulf; Established a science and technology working group with Mexican institutions centered in the State of Veracruz. Key team members include the Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), the Ecological Institute (INECOL) a unit of the National Council for science and technology (CONACYT), the Veracruz Aquarium (NOAA’s first international Coastal Ecology Learning Center) and the State of Veracruz. The Mexican Navy (critical to coastal studies in the Southern Gulf) and other national and regional entities have also been engaged; and Training on use of SERVIR portal planned for Fall 2007 in Veracruz, Mexico Science Applications; Worked with regional scientists to produce conceptual models of submerged aquatic vegetation (SAV) ecosystems; Built a logical framework and tool for ontological modeling of SAV and HABs; Created online guidance for SAV restoration planning; Created model runs which link potential future land use trends, runoff and SAV viability; Analyzed SAV

  10. Exploring star formation in high-z galaxies using atomic and molecular emission lines

    NASA Astrophysics Data System (ADS)

    Gullberg, Bitten

    2016-03-01

    The conditions under which stars are formed and the reasons for triggering and quenching of starburst events in high-z galaxies, are still not well understood. Studying the interstellar medium (ISM) and the morphology of high-z galaxies are therefore key points in order to understand galaxy evolution. The cosmic star formation rate density peaks between 1>1, and low to moderate [CII] optical depth tau(CII)<1. Combining millimetre/sub-millimetre and optical data cubes for the high-z radio galaxy (HzRG) MRC0943-242, has revealed a much more complicated morphology than seen in the individual data sets. The millimetre/sub-millimetre observations data have allowed us to spatially separate of the AGN and starburst dominated components, which ~65 kpc apart. The optical data reveal structures of emitting and absorbing gas at multiple wavelengths. A deep high resolution millimetre/sub-millimetre study of the HzRG MRC1138-262, shows emission from water (H2O) and an unusually large amount of neutral atomic carbon ([CI]) relative to highly excited CO compared to lensed DSFGs. The

  11. Rotenone-stimulated superoxide release from mitochondrial complex I acutely augments L-type Ca2+ current in A7r5 aortic smooth muscle cells.

    PubMed

    Ochi, Rikuo; Dhagia, Vidhi; Lakhkar, Anand; Patel, Dhara; Wolin, Michael S; Gupte, Sachin A

    2016-05-01

    Voltage-gated L-type Ca(2+) current (ICa,L) induces contraction of arterial smooth muscle cells (ASMCs), and ICa,L is increased by H2O2 in ASMCs. Superoxide released from the mitochondrial respiratory chain (MRC) is dismutated to H2O2 We studied whether superoxide per se acutely modulates ICa,L in ASMCs using cultured A7r5 cells derived from rat aorta. Rotenone is a toxin that inhibits complex I of the MRC and increases mitochondrial superoxide release. The superoxide content of mitochondria was estimated using mitochondrial-specific MitoSOX and HPLC methods, and was shown to be increased by a brief exposure to 10 μM rotenone. ICa,L was recorded with 5 mM BAPTA in the pipette solution. Rotenone administration (10 nM to 10 μM) resulted in a greater ICa,L increase in a dose-dependent manner to a maximum of 22.1% at 10 μM for 1 min, which gradually decreased to 9% after 5 min. The rotenone-induced ICa,L increase was associated with a shift in the current-voltage relationship (I-V) to a hyperpolarizing direction. DTT administration resulted in a 17.9% increase in ICa,L without a negative shift in I-V, and rotenone produced an additional increase with a shift. H2O2 (0.3 mM) inhibited ICa,L by 13%, and additional rotenone induced an increase with a negative shift. Sustained treatment with Tempol (4-hydroxy tempo) led to a significant ICa,L increase but it inhibited the rotenone-induced increase. Staurosporine, a broad-spectrum protein kinase inhibitor, partially inhibited ICa,L and completely suppressed the rotenone-induced increase. Superoxide released from mitochondria affected protein kinases and resulted in stronger ICa,L preceding its dismutation to H2O2 The removal of nitric oxide is a likely mechanism for the increase in ICa,L. PMID:26873970

  12. Development and Initial Evaluation of the Web-Based Self-Management Program “Partner in Balance” for Family Caregivers of People With Early Stage Dementia: An Exploratory Mixed-Methods Study

    PubMed Central

    de Vugt, Marjolein E; Withagen, Hanneke EJ; Kempen, Gertrudis IJM; Verhey, Frans RJ

    2016-01-01

    Background People with dementia increasingly depend on informal caregivers. Internet-based self-management interventions hold considerable promise for meeting the educational and support needs of early stage dementia caregivers (EDCs) at a reduced cost. Objective This study aimed to (1) develop an online self-management program for EDC to increase self-efficacy and goal attainment, and (2) evaluate the program’s feasibility and report preliminary data on effectiveness. Methods Based on the Medical Research Council (MRC) framework for the development and evaluation of complex interventions, a stepwise approach was adopted to explore potential user needs and develop and validate the content by means of (1) focus group discussions with dementia caregivers (N=28), (2) interviews with dementia care professionals (N=11), and (3) individual think-aloud usability tests with EDC (N=2) and experts (N=2). A pilot evaluation was conducted with EDC (N=17) to test the feasibility and establish preliminary effects. Self-report measures of feasibility were completed after the completion of intervention. Self-efficacy and goal attainment were evaluated before and after the intervention. Results The different steps provided useful information about the needs of potential users regarding the content and delivery of the program. This resulted in the newly developed “Partner in Balance” program. At the start, system failures resulted in a high noncompleter rate (7/17, 41%), but at the end, an acceptable feasibility score of 209 (range 54-234) was found. The convenience of completing the program at home, the tailored content, and the guidance (face-to-face and online) were appraised positively. Preliminary effects on caregiver self-efficacy (P<.05) and goal attainment (T>50) were promising. Conclusions Adaptations were made to the program to limit the amount of system failures and prevent high noncompleter rates. As recommended by the MRC framework, confirming the feasibility and

  13. Self-reported symptoms of chronic cough and breathlessness in working-age men in the city of Izhevsk, Russia: associations with cardiovascular disease risk factors and comorbidities

    PubMed Central

    Cook, Sarah; Quint, Jennifer K; Vasiljev, Maxim; Leon, David A

    2015-01-01

    Introduction Very little is known about the prevalence of respiratory symptoms or their associations with other health conditions in Russia. Methods Between 2008 and 2010, a sample of 983 men resident in Izhevsk, Russia, took part in a cross-sectional survey. Presence of respiratory symptoms was determined from self-report of chronic productive cough and breathlessness assessed using the British Medical Research Council (MRC) breathlessness scale. Self-reported physical and mental health were measured using the 12-Item Short-Form Health Survey (SF-12). Hypertension was assessed from mean blood pressure measured at the health check and/or self-reported use of antihypertensive medication. Other comorbidities were assessed from self-report. Logistic regression models were fitted assessing the association between respiratory symptoms and comorbidities. Linear regression models were fitted to investigate the association between respiratory symptoms and self-reported health scores. All models were adjusted for age, education and smoking status. Results The age-standardised prevalence of cough and breathlessness was 20.9% (prevalence with breathlessness MRC grade 3 or above 3.7%). The majority of men with respiratory symptoms (87.3%) were current smokers. Cough and breathlessness were associated with substantially worse self-reported physical and mental health (test for trend with severity of breathlessness p<0.001). Those with chronic cough and grade 3 or above breathlessness had higher odds of having hypertension (OR 3.03; 95% CI 1.36 to 6.74), diabetes (OR 10.55; 95% CI 2.69 to 41.37), angina pectoris (OR 7.54; 95% CI 3.61 to 15.73), previous myocardial infarction (OR 7.61; 95% CI 2.10 to 27.4) and previous stroke (OR 6.61; 95% CI 1.75 to 23.34) compared with those without respiratory symptoms. Conclusions The prevalence of respiratory symptoms was high. Strong associations were found between respiratory symptoms and cardiovascular comorbidities. These are of

  14. Occupational Exposures Are Associated with Worse Morbidity in Patients with Chronic Obstructive Pulmonary Disease

    PubMed Central

    Paulin, Laura M.; Diette, Gregory B.; Blanc, Paul D.; Putcha, Nirupama; Eisner, Mark D.; Kanner, Richard E.; Belli, Andrew J.; Christenson, Stephanie; Tashkin, Donald P.; Han, MeiLan; Barr, R. Graham

    2015-01-01

    Rationale: Links between occupational exposures and morbidity in individuals with established chronic obstructive pulmonary disease (COPD) remain unclear. Objectives: To determine the impact of occupational exposures on COPD morbidity. Methods: A job exposure matrix (JEM) determined occupational exposure likelihood based on longest job in current/former smokers (n = 1,075) recruited as part of the Subpopulations and Intermediate Outcomes in COPD Study, of whom 721 had established COPD. Bivariate and multivariate linear regression models estimated the association of occupational exposure with COPD, and among those with established disease, the occupational exposure associations with 6-minute-walk distance (6MWD), the Modified Medical Research Council Dyspnea Scale (mMRC), the COPD Assessment Test (CAT), St. George’s Respiratory Questionnaire (SGRQ), 12-item Short-Form Physical Component (SF-12), and COPD exacerbations requiring health care utilization, adjusting for demographics, current smoking status, and cumulative pack-years. Measurements and Main Results: An intermediate/high risk of occupational exposure by JEM was found in 38% of participants. In multivariate analysis, those with job exposures had higher odds of COPD (odds ratio, 1.44; 95% confidence interval, 1.04–1.97). Among those with COPD, job exposures were associated with shorter 6MWDs (−26.0 m; P = 0.006); worse scores for mMRC (0.23; P = 0.004), CAT (1.8; P = 0.003), SGRQ (4.5; P = 0.003), and SF-12 Physical (−3.3; P < 0.0001); and greater odds of exacerbation requiring health care utilization (odds ratio, 1.55; P = 0.03). Conclusions: Accounting for smoking, occupational exposure was associated with COPD risk and, for those with established disease, shorter walk distance, greater breathlessness, worse quality of life, and increased exacerbation risk. Clinicians should obtain occupational histories from patients with COPD because work-related exposures may

  15. Contrasting disease patterns in seropositive and seronegative neuromyelitis optica: A multicentre study of 175 patients

    PubMed Central

    2012-01-01

    Background The diagnostic and pathophysiological relevance of antibodies to aquaporin-4 (AQP4-Ab) in patients with neuromyelitis optica spectrum disorders (NMOSD) has been intensively studied. However, little is known so far about the clinical impact of AQP4-Ab seropositivity. Objective To analyse systematically the clinical and paraclinical features associated with NMO spectrum disorders in Caucasians in a stratified fashion according to the patients' AQP4-Ab serostatus. Methods Retrospective study of 175 Caucasian patients (AQP4-Ab positive in 78.3%). Results Seropositive patients were found to be predominantly female (p < 0.0003), to more often have signs of co-existing autoimmunity (p < 0.00001), and to experience more severe clinical attacks. A visual acuity of ≤ 0.1 during acute optic neuritis (ON) attacks was more frequent among seropositives (p < 0.002). Similarly, motor symptoms were more common in seropositive patients, the median Medical Research Council scale (MRC) grade worse, and MRC grades ≤ 2 more frequent, in particular if patients met the 2006 revised criteria (p < 0.005, p < 0.006 and p < 0.01, respectively), the total spinal cord lesion load was higher (p < 0.006), and lesions ≥ 6 vertebral segments as well as entire spinal cord involvement more frequent (p < 0.003 and p < 0.043). By contrast, bilateral ON at onset was more common in seronegatives (p < 0.007), as was simultaneous ON and myelitis (p < 0.001); accordingly, the time to diagnosis of NMO was shorter in the seronegative group (p < 0.029). The course of disease was more often monophasic in seronegatives (p < 0.008). Seropositives and seronegatives did not differ significantly with regard to age at onset, time to relapse, annualized relapse rates, outcome from relapse (complete, partial, no recovery), annualized EDSS increase, mortality rate, supratentorial brain lesions, brainstem lesions, history of carcinoma, frequency of preceding infections, oligoclonal bands, or CSF

  16. Initiation of the Fiordland-Puysegur subduction zone, New Zealand

    NASA Astrophysics Data System (ADS)

    Mao, X.; Gurnis, M.; May, D.

    2014-12-01

    The Australia-Pacific plate boundary south of New Zealand was an active ridge 45 Ma to 30 Ma, generating oceanic crust between the Resolution Rifted Margin and the Campbell Rifted Margin. Referred to as the Macquarie Ridge Complex (MRC), this boundary progressively evolved into a strike-slip boundary from 30 Ma to 20 Ma; the northern segment, the Fiordland-Puysegur subduction zone (FPSZ), has had a substantial transpressional component. Over the last 20 Myr, 600 km of highly oblique plate motion occurred at the MRC, and resulted in a maximum total convergence of 150-200 km at the FPSZ, which some simple models suggested might be near the threshold for a self-sustaining subduction. The morphology of the Puysegur Ridge shows a diagnostic change from uplift to subsidence expected for the transition of a subduction zone from being forced externally to being internally driven by the negative buoyancy of the slab. The large negative gravity anomalies over the Snares Zone, in the middle of the FPSZ, imply strong vertical forces pulling downward the lithosphere. To better understand these observations, we use a viscous flow forward model with a free surface to simulate the geodynamics of the FPSZ since 20 Ma. The forward model describes the dynamics of an incompressible, Stokes fluid. Brittle-ductile behavior of the material within the crust-asthenosphere is modeled by using a fluid viscosity defined via a composite flow law comprised from an Arrhenius and a Drucker-Prager rheology. The well-constrained relative plate motion between the Australian and Pacific plates is used to define a Dirichlet boundary condition for velocity within the lithosphere. In the mantle, we apply the hydrostatic pressure as a normal stress boundary condition. A simplified surface process model consisting of linear diffusion is applied at the free surface to simulate short-range erosion and sedimentation. Our models show that the topographic variations within the Puysegur Ridges may correspond to

  17. Essential Oil of Cymbopogon nardus (L.) Rendle: A Strategy to Combat Fungal Infections Caused by Candida Species

    PubMed Central

    De Toledo, Luciani Gaspar; Ramos, Matheus Aparecido Dos Santos; Spósito, Larissa; Castilho, Elza Maria; Pavan, Fernando Rogério; Lopes, Érica De Oliveira; Zocolo, Guilherme Julião; Silva, Francisca Aliny Nunes; Soares, Tigressa Helena; dos Santos, André Gonzaga; Bauab, Taís Maria; De Almeida, Margarete Teresa Gottardo

    2016-01-01

    Background: The incidence of fungal infections, especially those caused by Candida yeasts, has increased over the last two decades. However, the indicated therapy for fungal control has limitations. Hence, medicinal plants have emerged as an alternative in the search for new antifungal agents as they present compounds, such as essential oils, with important biological effects. Published data demonstrate important pharmacological properties of the essential oil of Cymbopogon nardus (L.) Rendle; these include anti-tumor, anti-nociceptive, and antibacterial activities, and so an investigation of this compound against pathogenic fungi is interesting. Objective: The aim of this study was to evaluate the chemical composition and biological potential of essential oil (EO) obtained from the leaves of C. nardus focusing on its antifungal profile against Candida species. Methods: The EO was obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS). Testing of the antifungal potential against standard and clinical strains was performed by determining the minimal inhibitory concentration (MIC), time-kill, inhibition of Candida albicans hyphae growth, and inhibition of mature biofilms. Additionally, the cytotoxicity was investigated by the IC50 against HepG-2 (hepatic) and MRC-5 (fibroblast) cell lines. Results: According to the chemical analysis, the main compounds of the EO were the oxygen-containing monoterpenes: citronellal, geranial, geraniol, citronellol, and neral. The results showed important antifungal potential for all strains tested with MIC values ranging from 250 to 1000 μg/mL, except for two clinical isolates of C. tropicalis (MIC > 1000 μg/mL). The time-kill assay showed that the EO inhibited the growth of the yeast and inhibited hyphal formation of C. albicans strains at concentrations ranging from 15.8 to 1000 μg/mL. Inhibition of mature biofilms of strains of C. albicans, C. krusei and C. parapsilosis occurred at a

  18. Outcomes associated with acute exacerbations of chronic obstructive pulmonary disorder requiring hospitalization

    PubMed Central

    Gaude, Gajanan S; Rajesh, BP; Chaudhury, Alisha; Hattiholi, Jyothi

    2015-01-01

    Background: Acute exacerbations of chronic obstructive pulmonary disorder (AECOPD) are known to be associated with increased morbidity and mortality and have a significant socioeconomic impact. The factors that determine frequent hospital readmissions for AECOPD are poorly understood. The present study was done to ascertain failures rates following AECOPD and to evaluate factors associated with frequent readmissions. Materials and Methods: We conducted a prospective study among 186 patients with COPD with one or more admissions for acute exacerbations in a tertiary care hospital. Frequency of previous re-admissions for AECOPD in the past year, and clinical characteristics, including spirometry were ascertained in the stable state both before discharge and at 6-month post-discharge. Failure rates following treatment were ascertained during the follow-up period. All the patients were followed up for a period of 2 years after discharge to evaluate re-admissions for the AECOPD. Results: Of 186 COPD patients admitted for AECOPD, 54% had one or more readmission, and another 45% had two or more readmissions over a period of 2 years. There was a high prevalence of current or ex-heavy smokers, associated co-morbidity, underweight patients, low vaccination prevalence and use of domiciliary oxygen therapy among COPD patients. A total of 12% mortality was observed in the present study. Immediate failure rates after first exacerbation was observed to be 34.8%. Multivariate analysis showed that duration >20 years (OR = 0.37; 95% CI: 0.10-0.86), use of Tiotropium (OR = 2.29; 95% CI: 1.12-4.69) and use of co-amoxiclav during first admission (OR = 2.41; 95% CI: 1.21-4.79) were significantly associated with higher immediate failure rates. The multivariate analysis for repeated admissions revealed that disease duration >10 years (OR = 0.50; 95% CI: 0.27-0.93), low usage of inhaled ICS + LABA (OR = 2.21; 95% CI: 1.08-4.54), and MRC dyspnea grade >3 (OR = 2.51; 95% CI: 1.08-5.82) were

  19. An excess of dusty starbursts related to the Spiderweb galaxy

    NASA Astrophysics Data System (ADS)

    Dannerbauer, H.; Kurk, J. D.; De Breuck, C.; Wylezalek, D.; Santos, J. S.; Koyama, Y.; Seymour, N.; Tanaka, M.; Hatch, N.; Altieri, B.; Coia, D.; Galametz, A.; Kodama, T.; Miley, G.; Röttgering, H.; Sanchez-Portal, M.; Valtchanov, I.; Venemans, B.; Ziegler, B.

    2014-10-01

    We present APEX LABOCA 870 μm observations of the field around the high-redshift radio galaxy MRC1138-262 at z = 2.16. We detect 16 submillimeter galaxies (SMGs) in this ~140 arcmin2 bolometer map with flux densities in the range 3-11 mJy. The raw number counts indicate a density of SMGs that is up to four times that of blank field surveys. Based on an exquisite multiwavelength database, including VLA 1.4 GHz radio and infrared observations, we investigate whether these sources are members of the protocluster structure at z ≈ 2.2. Using Herschel PACS and SPIRE and Spitzer MIPS photometry, we derive reliable far-infrared (FIR) photometric redshifts for all sources. Follow-up VLT ISAAC and SINFONI NIR spectra confirm that four of these SMGs have redshifts of z ≈ 2.2. We also present evidence that another SMG in this field, detected earlier at 850 μm, has a counterpart that exhibits Hα and CO(1-0) emission at z = 2.15. Including the radio galaxy and two SMGs with FIR photometric redshifts at z = 2.2, we conclude that at least eight submm sources are part of the protocluster at z = 2.16 associated with the radio galaxy MRC1138-262. We measure a star formation rate density SFRD ~1500 M⊙ yr-1 Mpc-3, four magnitudes higher than the global SFRD of blank fields at this redshift. Strikingly, these eight sources are concentrated within a region of 2 Mpc (the typical size of clusters in the local universe) and are distributed within the filaments traced by the HAEs at z ≈ 2.2. This concentration of massive, dusty starbursts is not centered on the submillimeter-bright radio galaxy which could support the infalling of these sources into the cluster center. Approximately half (6/11) of the SMGs that are covered by the Hα imaging data are associated with HAEs, demonstrating the potential of tracing SMG counterparts with this population. To summarize, our results demonstrate that submillimeter observations may enable us to study (proto)clusters of massive, dusty

  20. Physiological, molecular, and cellular mechanisms of impaired seawater tolerance following exposure of Atlantic salmon, Salmo salar, smolts to acid and aluminum

    USGS Publications Warehouse

    Monette, M.Y.; Yada, T.; Matey, V.; McCormick, S.D.

    2010-01-01

    We examined the physiological, molecular, and cellular mechanisms of impaired ion regulation in Atlantic salmon, Salmo salar, smolts following acute acid and aluminum (Al) exposure. Smolts were exposed to: control (pH 6.5, 3.4??gl-1 Al), acid and low Al (LAl: pH 5.4, 11??gl-1 Al), acid and moderate Al (MAl: pH 5.3, 42??gl-1 Al), and acid and high Al (HAl: pH 5.4, 56??gl-1 Al) for two and six days. At each time-point, smolts were sampled directly from freshwater treatment tanks and after a 24h seawater challenge. Exposure to acid/MAl and acid/HAl led to accumulation of gill Al, substantial alterations in gill morphology, reduced gill Na+/K+-ATPase (NKA) activity, and impaired ion regulation in both freshwater and seawater. Exposure to acid/MAl for six days also led to a decrease in gill mRNA expression of the apical Cl- channel (cystic fibrosis transmembrane conductance regulator I), increased apoptosis upon seawater exposure, an increase in the surface expression of mitochondria-rich cells (MRCs) within the filament epithelium of the gill, but reduced abundance of gill NKA-positive MRCs. By contrast, smolts exposed to acid and the lowest Al concentration exhibited minor gill Al accumulation, slight morphological modifications in the gill, and impaired seawater tolerance in the absence of a detectable effect on freshwater ion regulation. These impacts were accompanied by decreased cell proliferation, a slight increase in the surface expression of MRCs within the filament epithelium, but no impact on gill apoptosis or total MRC abundance was observed. However, MRCs in the gills of smolts exposed to acid/LAl exhibited morphological alterations including decreased size, staining intensity, and shape factor. We demonstrate that the seawater tolerance of Atlantic salmon smolts is extremely sensitive to acute exposure to acid and low levels of Al, and that the mechanisms underlying this depend on the time-course and severity of Al exposure. We propose that when smolts are

  1. Cytotoxic effect of Alpinia scabra (Blume) Náves extracts on human breast and ovarian cancer cells

    PubMed Central

    2013-01-01

    Background Alpinia scabra, locally known as 'Lengkuas raya’, is an aromatic, perennial and rhizomatous herb from the family Zingiberaceae. It is a wild species which grows largely on mountains at moderate elevations in Peninsular Malaysia, but it can also survive in the lowlands like in the states of Terengganu and Northern Johor. The present study reports the cytotoxic potential of A. scabra extracts from different parts of the plant. Methods The experimental approach in the present study was based on a bioassay-guided fractionation. The crude methanol and fractionated extracts (hexane, chloroform and water) from different parts of A. scabra (leaves, rhizomes, roots and pseudo stems) were prepared prior to the cytotoxicity evaluation against human ovarian (SKOV-3) and hormone-dependent breast (MCF7) carcinoma cells. The identified cytotoxic extracts were then subjected to chemical investigations in order to identify the active ingredients. A normal human lung fibroblast cell line (MRC-5) was used to determine the specificity for cancerous cells. The cytotoxic extracts and fractions were also subjected to morphological assessment, DNA fragmentation analysis and DAPI nuclear staining. Results The leaf (hexane and chloroform) and rhizome (chloroform) extracts showed high inhibitory effect against the tested cells. Ten fractions (LC1-LC10) were yielded after purification of the leaf chloroform extract. Fraction LC4 which showed excellent cytotoxic activity was further purified and resulted in 17 sub-fractions (VLC1-VLC17). Sub-fraction VLC9 showed excellent cytotoxicity against MCF7 and SKOV-3 cells but not toxic against normal MRC-5 cells. Meanwhile, eighteen fractions (RC1-RC18) were obtained after purification of the rhizome chloroform extract, of which fraction RC5 showed cytotoxicity against SKOV-3 cells with high selectivity index. There were marked morphological changes when observed using phase-contrast inverted microscope, DAPI nuclear staining and also DNA

  2. Polydimethylsiloxane SlipChip for mammalian cell culture applications.

    PubMed

    Chang, Chia-Wen; Peng, Chien-Chung; Liao, Wei-Hao; Tung, Yi-Chung

    2015-11-01

    This paper reports a polydimethylsiloxane (PDMS) SlipChip for in vitro cell culture applications, multiple-treatment assays, cell co-cultures, and cytokine detection assays. The PDMS SlipChip is composed of two PDMS layers with microfluidic channels on each surface that are separated by a thin silicone fluid (Si-fluid) layer. The integration of Si-fluid enables the two PDMS layers to be slid to different positions; therefore, the channel patterns can be re-arranged for various applications. The SlipChip design significantly reduces the complexity of sample handling, transportation, and treatment processes. To apply the developed SlipChip for cell culture applications, human lung adenocarcinoma epithelial cells (A549) and lung fibroblasts (MRC-5) were cultured to examine the biocompatibility of the developed PDMS SlipChip. Moreover, embryonic pluripotent stem cells (ES-D3) were also cultured in the device to evaluate the retention of their stemness in the device. The experimental results show that cell morphology, viability and proliferation are not affected when the cells are cultured in the SlipChip, indicating that the device is highly compatible with mammalian cell culture. In addition, the stemness of the ES-D3 cells was highly retained after they were cultured in the device, suggesting the feasibility of using the SlipChip for stem cell research. Various cell experiments, such as simultaneous triple staining of cells and co-culture of MRC-5 with A549 cells, were also performed to demonstrate the functionalities of the PDMS SlipChip. Furthermore, we used a cytokine detection assay to evaluate the effect of endotoxin (lipopolysaccharides, LPS) treatment on the cytokine secretion of A549 cells using the SlipChip. The developed PDMS SlipChip provides a straightforward and effective platform for various on-chip in vitro cell cultures and consequent analysis, which is promising for a number of cell biology studies and biomedical applications. PMID:26381390

  3. Enhancing capacities of riparian professionals to address and resolve transboundary issues in international river basins: experiences from the Lower Mekong River Basin

    NASA Astrophysics Data System (ADS)

    Douven, W.; Mul, M. L.; Álvarez, B. F.; Son, L. H.; Bakker, N.; Radosevich, G.; van der Zaag, P.

    2012-03-01

    This paper analyses the design and impact of capacity building programmes aimed at enhancing capacities of riparian professionals to address and resolve transboundary issues in international river basins. Case study is a programme developed by the Mekong River Commission (MRC). A post training evaluation was applied to assess its impact in terms of individual capacity enhancement and change (use and application of knowledge, factors hampering application, and change in function and opportunities within their organisation). The design of the Capacity Building Programme of the MRC Flood Management and Mitigation Programme showed a well balanced range of subjects (such as IWRM, models and decision support systems and international water law) which are required for such an integrated topic. The post training evaluation, 6 months after the last training workshop, showed the increase in familiarity of the topics for all 37 respondents, with highest increase for the respondents with few years of working experience and from training and educational institutions. The relevance of the subjects taught is shown by the fact that 95% of the respondents indicated they saw the relevance of the subjects and 78% had already used some knowledge acquired in their job. The respondents also indicated that they did not have sufficient opportunities to apply all knowledge acquired. The phased implementation and training of lecturers during the training workshops, had a good impact, directly through increasing involvement in facilitation and delivery of the capacity building programme and through the use of the knowledge gained in short courses and development of curricula at their training institute. For these types of capacity building programmes, a few recommendations can be made. The selection of participants is crucial for the application of the learned knowledge in their work. The integrative nature of transboundary water issues calls for a capacity building programme addressing a

  4. Symptoms and quality of life in patients with chronic obstructive pulmonary disease treated with aclidinium in a real-life setting

    PubMed Central

    Lange, Peter; Godtfredsen, Nina Skavlan; Olejnicka, Beata; Paradis, Bo-Anders; Curiac, Dan; Humerfelt, Sjur; Telg, Gunilla; Christensen, Helene Nordahl; Bitsch, Magnus Alexander; Andersen, Elisabeth Wreford; Bjermer, Leif

    2016-01-01

    Introduction Chronic obstructive pulmonary disease (COPD) is a progressive disease with symptoms that can have a major impact on patients’ physical health. The aim of this study was to evaluate quality of life (QoL), symptom severity and dyspnoea in COPD patients treated with aclidinium up to 24 weeks. Methods In this prospective non-interventional multicentre study (198 centres in Sweden, Denmark, and Norway), COPD patients (age ≥40 years) who started treatment with aclidinium (initial therapy, change of treatment, or add-on therapy) could be included. Health-related QoL was obtained by COPD assessment test (CAT). Symptoms were evaluated on a 6-point Likert scale. The modified Medical Research Council (mMRC) Dyspnoea Scale was used as a simple grading system to assess the level of dyspnoea/shortness of breath from0 to 4. Patients on treatment with aclidinium who completed baseline and at least one follow-up visit (week 12 or 24) were included in the study population. Results Overall, 1,093 patients were enrolled (mean 69 years, 54% females), one-third had ≥1 exacerbation the year prior to baseline. At enrolment, 48% were LAMA naïve. Mean (standard deviation, SD) CAT score decreased from 16.9 (7.7) at baseline to 14.3 (7.3) at week 24 (p<0.01) with a decrease in all individual CAT items (p<0.05). Mean difference in morning and night-time symptoms from baseline to week 24 was −0.60 (SD 2.51) and −0.44 (SD 2.48), respectively (both p<0.001). Mean (SD) mMRC Dyspnoea Scale changed from 1.6 (1.0) at baseline to 1.5 (1.0) at week 24 (p<0.001). Conclusion In this observational study of a Nordic real-life COPD population, treatment with aclidinium was associated with a clinically important improvement in QoL and morning and night-time symptoms, most pronounced in the LAMA naïve group. However, there is still room for improvement in the management of symptomatic COPD patients. PMID:27387608

  5. Physiological, molecular, and cellular mechanisms of impaired seawater tolerance following exposure of Atlantic salmon, Salmo salar, smolts to acid and aluminum.

    PubMed

    Monette, Michelle Y; Yada, Takashi; Matey, Victoria; McCormick, Stephen D

    2010-08-01

    We examined the physiological, molecular, and cellular mechanisms of impaired ion regulation in Atlantic salmon, Salmo salar, smolts following acute acid and aluminum (Al) exposure. Smolts were exposed to: control (pH 6.5, 3.4 micrpg l(-1) Al), acid and low Al (LAl: pH 5.4, 11 microg l(-1) Al), acid and moderate Al (MAl: pH 5.3, 42 microg l(-1) Al), and acid and high Al (HAl: pH 5.4, 56 microg l(-1) Al) for two and six days. At each time-point, smolts were sampled directly from freshwater treatment tanks and after a 24h seawater challenge. Exposure to acid/MAl and acid/HAl led to accumulation of gill Al, substantial alterations in gill morphology, reduced gill Na(+)/K(+)-ATPase (NKA) activity, and impaired ion regulation in both freshwater and seawater. Exposure to acid/MAl for six days also led to a decrease in gill mRNA expression of the apical Cl(-) channel (cystic fibrosis transmembrane conductance regulator I), increased apoptosis upon seawater exposure, an increase in the surface expression of mitochondria-rich cells (MRCs) within the filament epithelium of the gill, but reduced abundance of gill NKA-positive MRCs. By contrast, smolts exposed to acid and the lowest Al concentration exhibited minor gill Al accumulation, slight morphological modifications in the gill, and impaired seawater tolerance in the absence of a detectable effect on freshwater ion regulation. These impacts were accompanied by decreased cell proliferation, a slight increase in the surface expression of MRCs within the filament epithelium, but no impact on gill apoptosis or total MRC abundance was observed. However, MRCs in the gills of smolts exposed to acid/LAl exhibited morphological alterations including decreased size, staining intensity, and shape factor. We demonstrate that the seawater tolerance of Atlantic salmon smolts is extremely sensitive to acute exposure to acid and low levels of Al, and that the mechanisms underlying this depend on the time-course and severity of Al

  6. The transfer of seasonal isotopic variability between precipitation and drip water at eight caves in the monsoon regions of China

    NASA Astrophysics Data System (ADS)

    Duan, Wuhui; Ruan, Jiaoyang; Luo, Weijun; Li, Tingyong; Tian, Lijun; Zeng, Guangneng; Zhang, Dezhong; Bai, Yijun; Li, Jilong; Tao, Tao; Zhang, Pingzhong; Baker, Andy; Tan, Ming

    2016-06-01

    This study presents new stable isotope data for precipitation (δ18Op) and drip water (δ18Od) from eight cave sites in the monsoon regions of China (MRC), with monthly to bi-monthly sampling intervals from May-2011 to April-2014, to investigate the regional-scale climate forcing on δ18Op and how the isotopic signals are transmitted to various drip sites. The monthly δ18Op values show negative correlation with surface air temperature at all the cave sites except Shihua Cave, which is opposite to that expected from the temperature effect. In addition, although the monthly δ18Op values are negatively correlated with precipitation at all the cave sites, only three sites are significant at the 95% level. These indicate that, due to the various vapor sources, a large portion of variability in δ18Op in the MRC cannot be explained simply by either temperature or precipitation alone. All the thirty-four drip sites are classified into three types based on the δ18Od variability. About 82% of them are static drips with little discernable variation in δ18Od through the whole study period, but the drip rates of these drips are not necessary constant. Their discharge modes are site-specific and the oxygen isotopic composition of the stalagmites growing from them may record the average of multi-year climatic signals, which are modulated by the seasonality of recharge and potential effects of evaporation, and in some cases infiltration from large rainfall events. About 12% of the thirty-four drip sites are seasonal drips, although the amplitude of δ18Od is narrower than that of δ18Op, the monthly response of δ18Od to coeval precipitation is not completely damped, and some of them follow the seasonal trend of δ18Op very well. These drips may be mainly recharged by present-day precipitation, mixing with some stored water. Thus, the stalagmites growing under them may record portions of the seasonal climatic signals embedded in δ18Op. About 6% of the thirty-four drip sites

  7. Synthesis, structural characterization and biological studies of the triphenyltin(IV) complex with 2-thiobarbituric acid.

    PubMed

    Balas, V I; Verginadis, I I; Geromichalos, G D; Kourkoumelis, N; Male, L; Hursthouse, M B; Repana, K H; Yiannaki, E; Charalabopoulos, K; Bakas, T; Hadjikakou, S K

    2011-07-01

    The reaction between 2-thiobarbituric acid (H(2)TBA), which was treated with an equimolar amount of potassium hydroxide, in a water with triphenytin chloride in methanol, results in the formation of the {[Ph(3)Sn(O-HTBA)]}(n) (1) complex. Crystals of the hydrated 1 with formula {[Ph(3)Sn(O-HTBA)]·0.7(H(2)O)}(n) were growth from methanol/acetonitrile solution, of the white precipitation, filtered off, from the reaction. The crystal structure of complex 1 has been determined by X-ray diffraction at 120 K. Complex 1 is polymeric. The geometry around the tin(IV) ions is trigonal bi-pyramidal with coordination to three C atoms from phenyl groups and one O atom from a de-protonated HTBA ligand. Complex 1 and the already known [(n-Bu)(3)Sn(O-HTBA)·H(2)O] (2) were evaluated for their in vitro cytotoxic activity (cell viability) against human cancer cell lines: HeLa (cervical), OAW-42 (ovarian), MCF-7 (breast, ER positive), MDA-MB-231 (breast, ER negative), A549 (lung), Caki-1 (renal) and additionally, the normal human lung cell line MRC-5 (normal human fetal lung fibroblast cells) and normal immortalized human mammary gland epithelial cell line MTSV17 with a Trypan Blue assay. Moreover complex 1 was evaluated for its in vitro cell growth proliferation activity against leiomyosarcoma cells (LMS), MCF-7 and MRC-5 cells with a Thiazolyl Blue Tetrazolium Bromide (MTT) assay. The type of cell death caused by complexes 1 and 2 was also evaluated by use of flow cytometry assay. The results showed that these compounds mediate a strong cytotoxic response to normal and cancer cell lines tested through apoptosis and induce cell cycle arrest in S phase of the cell cycle, suggesting DNA intercalation (direct or indirect) with the complexes. Finally, the influence of these complexes 1 and 2 upon the catalytic peroxidation of linoleic acid to hydroperoxylinoleic acid by the enzyme lipoxygenase (LOX) was kinetically and theoretically studied. PMID:21521629

  8. RT-qPCR-based microneutralization assay for human cytomegalovirus using fibroblasts and epithelial cells.

    PubMed

    Wang, Xiao; Peden, Keith; Murata, Haruhiko

    2015-12-16

    Human cytomegalovirus (HCMV) is a leading cause of congenital infection that can result in serious disabilities in affected children. To facilitate HCMV vaccine development, a microscale neutralization assay based on reverse transcription quantitative PCR (RT-qPCR) was developed to quantify HCMV-neutralizing antibodies. Our approach relies on the generation of crude lysates from virus-infected cells that are amenable to direct analysis by RT-qPCR, thereby circumventing rate-limiting procedures associated with sample RNA extraction and purification. By serial passaging of the laboratory HCMV strain AD169 in epithelial cells (ARPE-19), a revertant virus with restored epithelial cell tropism, designated AD169(wt131), was obtained. AD169 and AD169(wt131) were evaluated in both epithelial cells (ARPE-19) and fibroblasts (MRC-5) by one-step RT-qPCR targeting the immediate-early gene IE1 transcript of HCMV. Expression kinetics indicated that RT-qPCR assessment could be conducted as early as 6h post-infection. Human serum samples (n=30) from healthy donors were tested for HCMV-specific IgG using a commercially available ELISA and for HCMV-neutralizing activity using our RT-qPCR-based neutralization assay. In agreement with the ELISA results, higher neutralizing activity was observed in the HCMV IgG seropositive group when compared with the HCMV IgG seronegative group. In addition, HCMV IgG seropositive human sera exhibited higher neutralizing titers using epithelial cells compared with using fibroblasts (geometric mean titers of 344 and 8 in ARPE-19 cells and MRC-5 cells, respectively). Our assay was robust to variation in input virus dose. In addition, a simple lysis buffer containing a non-ionic detergent was successfully demonstrated to be a less costly alternative to commercial reagents for cell-lysate preparation. Thus, our rapid HCMV neutralization assay may be a straightforward and flexible high-throughput tool for measuring antibody responses induced by vaccination

  9. Interactions between hypoxia tolerance and food deprivation in Amazonian oscars, Astronotus ocellatus.

    PubMed

    De Boeck, Gudrun; Wood, Chris M; Iftikar, Fathima I; Matey, Victoria; Scott, Graham R; Sloman, Katherine A; de Nazaré Paula da Silva, Maria; Almeida-Val, Vera M F; Val, Adalberto L

    2013-12-15

    Oscars are often subjected to a combination of low levels of oxygen and fasting during nest-guarding on Amazonian floodplains. We questioned whether this anorexia would aggravate the osmo-respiratory compromise. We compared fed and fasted oscars (10-14 days) in both normoxia and hypoxia (10-20 Torr, 4 h). Routine oxygen consumption rates (O2) were increased by 75% in fasted fish, reflecting behavioural differences, whereas fasting improved hypoxia resistance and critical oxygen tensions (Pcrit) lowered from 54 Torr in fed fish to 34 Torr when fasting. In fed fish, hypoxia reduced liver lipid stores by approximately 50% and total liver energy content by 30%. Fasted fish had a 50% lower hepatosomatic index, resulting in lower total liver protein, glycogen and lipid energy stores under normoxia. Compared with hypoxic fed fish, hypoxic fasted fish only showed reduced liver protein levels and even gained glycogen (+50%) on a per gram basis. This confirms the hypothesis that hypoxia-tolerant fish protect their glycogen stores as much as possible as a safeguard for more prolonged hypoxic events. In general, fasted fish showed lower hydroxyacylCoA dehydrogenase activities compared with fed fish, although this effect was only significant in hypoxic fasted fish. Energy stores and activities of enzymes related to energy metabolism in muscle or gills were not affected. Branchial Na(+) uptake rates were more than two times lower in fed fish, whereas Na(+) efflux was similar. Fed and fasted fish quickly reduced Na(+) uptake and efflux during hypoxia, with fasting fish responding more rapidly. Ammonia excretion and K(+) efflux were reduced under hypoxia, indicating decreased transcellular permeability. Fasted fish had more mitochondria-rich cells (MRC), with larger crypts, indicating the increased importance of the branchial uptake route when feeding is limited. Gill MRC density and surface area were greatly reduced under hypoxia, possibly to reduce ion uptake and efflux rates

  10. Magnetoencephalography to investigate central perception of exercise-induced breathlessness in people with chronic lung disease: a feasibility pilot

    PubMed Central

    Johnson, Miriam J; Simpson, Michael IG; Currow, David C; Millman, Rebecca E; Hart, Simon P; Green, Gary

    2015-01-01

    Objectives Neuroimaging in chronic breathlessness is challenging. The study objective was to test the feasibility of magnetoencephalography (MEG) for functional neuroimaging of people with chronic breathlessness. Design Feasibility pilot study. Setting Respiratory clinic out-patients. Participants 8 patients (mean age=62; (range 47–83); 4 men) with chronic non-malignant lung disease; modified MRC breathlessness score ≥3 (median mMRC=4), intensity of exercise-induced breathlessness >3/10; no contraindication to MRI scanning. Methods and measures 4 MEG scans were conducted for each participant: (1) at rest (5 mins), (2) postseated leg exercise-induced breathlessness during recovery (10 mins). Recovery scans (2) were conducted with/without facial airflow in random order; both scans were repeated 1 h later. Participants rated breathlessness intensity (0–10 Numerical Rating Scale (NRS)) at baseline, maximal exertion and every minute during recovery, and rated acceptability of study procedures at the end of the study (0–10 NRS). A structural MRI scan was conducted for MEG coregistration and source-space analyses. Rest data were compared with data from healthy volunteers (N=6; 5 men; mean age=30.7 years±3.9 years). Results Exercises and MEG scanning were acceptable to all participants; 7/8 completed the MRI scans. Maximum breathlessness intensity was induced by 5 min’ exercise. The same level was induced for repeat scans (median=8; IQR=7–8). All recovered to baseline by 10 min. Time-frequency profiles of data from the first and last 3 min were analysed in MEG source space based on breathlessness location estimates. Source localisation was performed, but anatomical source inference was limited to the level of the lobe. Differences in areas of activity were seen: during recovery scans; with and without airflow; and between participants/normal volunteers at rest. Conclusions MEG is a feasible method to investigate exercise-induced breathlessness

  11. A two-decade comparison of prevalence of dementia in individuals aged 65 years and older from three geographical areas of England: results of the Cognitive Function and Ageing Study I and II

    PubMed Central

    Matthews, Fiona E; Arthur, Antony; Barnes, Linda E; Bond, John; Jagger, Carol; Robinson, Louise; Brayne, Carol

    2013-01-01

    Summary Background The prevalence of dementia is of interest worldwide. Contemporary estimates are needed to plan for future care provision, but much evidence is decades old. We aimed to investigate whether the prevalence of dementia had changed in the past two decades by repeating the same approach and diagnostic methods as used in the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS) in three of the original study areas in England. Methods Between 1989 and 1994, MRC CFAS investigators did baseline interviews in populations aged 65 years and older in six geographically defined areas in England and Wales. A two stage process, with screening followed by diagnostic assessment, was used to obtain data for algorithmic diagnoses (geriatric mental state–automated geriatric examination for computer assisted taxonomy), which were then used to estimate dementia prevalence. Data from three of these areas—Cambridgeshire, Newcastle, and Nottingham—were selected for CFAS I. Between 2008 and 2011, new fieldwork was done in the same three areas for the CFAS II study. For both CFAS I and II, each area needed to include 2500 individuals aged 65 years and older to provide power for geographical and generational comparison. Sampling was stratified according to age group (65–74 years vs ≥75 years). CFAS II used identical sampling, approach, and diagnostic methods to CFAS I, except that screening and assessement were combined into one stage. Prevalence estimates were calculated using inverse probability weighting methods to adjust for sampling design and non-response. Full likelihood Bayesian models were used to investigate informative non-response. Findings 7635 people aged 65 years or older were interviewed in CFAS I (9602 approached, 80% response) in Cambridgeshire, Newcastle, and Nottingham, with 1457 being diagnostically assessed. In the same geographical areas, the CFAS II investigators interviewed 7796 individuals (14 242 approached, 242 with

  12. Estimating of suspended sediment loads of rivers in the Seine downstream basin and coastal rivers in Southeastern Channel

    NASA Astrophysics Data System (ADS)

    Landemaine, Valentin; Cerdan, Olivier; Laignel, Benoit; Fournier, Matthieu; Copard, Yoann

    2014-05-01

    and multi sediment rating curve (MRC). From the results, the MRC algorithm had the best performance in terms of bias and precision between real and estimated sediment loads. This algorithm has been used to determine the sediment loads of all watersheds. On the Seine downstream basin, sediment fluxes from tributaries range from 171,000 t/year to 945,000 t/year depending on the year. This represents between 3% and 9% of sediment fluxes passing into the Seine. Finally, the long term variability analysis showed a high variability from year to year depending on climatic conditions. This study suggests the need to investigate fluxes over several years, to extract representative orders of magnitude and to quantify uncertainties.

  13. Green synthesis of bacterial mediated anti-proliferative gold nanoparticles: inducing mitotic arrest (G2/M phase) and apoptosis (intrinsic pathway)

    NASA Astrophysics Data System (ADS)

    Ganesh Kumar, C.; Poornachandra, Y.; Chandrasekhar, Cheemalamarri

    2015-11-01

    The physiochemical and biological properties of microbial derived gold nanoparticles have potential applications in various biomedical domains as well as in cancer therapy. We have fabricated anti-proliferative bacterial mediated gold nanoparticles (b-Au NPs) using a culture supernatant of Streptomyces clavuligerus and later characterized them by UV-visible, TEM, DLS, XRD and FT-IR spectroscopic techniques. The capping agent responsible for the nanoparticle formation was characterized based on SDS-PAGE and MALDI-TOF-MS analyses. They were tested for anticancer activity in A549, HeLa and DU145 cell lines. The biocompatibility and non-toxic nature of the nanoparticles were tested on normal human lung cell line (MRC-5). The b-Au NPs induced the cell cycle arrest in G2/M phase and also inhibited the microtubule assembly in DU145 cells. Mechanistic studies, such as ROS, MMP, Cyt-c, GSH, caspases 9, 8 and 3 activation and the Annexin V-FITC staining, along with the above parameters tested provided sufficient evidence that the b-Au NPs induced apoptosis through the intrinsic pathway. The results supported the use of b-Au NPs for future therapeutic application in cancer therapy and other biomedical applications.The physiochemical and biological properties of microbial derived gold nanoparticles have potential applications in various biomedical domains as well as in cancer therapy. We have fabricated anti-proliferative bacterial mediated gold nanoparticles (b-Au NPs) using a culture supernatant of Streptomyces clavuligerus and later characterized them by UV-visible, TEM, DLS, XRD and FT-IR spectroscopic techniques. The capping agent responsible for the nanoparticle formation was characterized based on SDS-PAGE and MALDI-TOF-MS analyses. They were tested for anticancer activity in A549, HeLa and DU145 cell lines. The biocompatibility and non-toxic nature of the nanoparticles were tested on normal human lung cell line (MRC-5). The b-Au NPs induced the cell cycle arrest in G2

  14. Implications for osmorespiratory compromise by anatomical remodeling in the gills of Arapaima gigas.

    PubMed

    Ramos, Cleverson Agner; Fernandes, Marisa Narciso; da Costa, Oscar Tadeu Ferreira; Duncan, Wallice Paxiuba

    2013-10-01

    The gill structure of the Amazonian fish Arapaima gigas, an obligatory air breather, was investigated during its transition from water breathing to the obligatory air breathing modes of respiration. The gill structure of A. gigas larvae is similar to that of most teleost fish; however, the morphology of the gills changes as the fish grow. The main morphological changes in the gill structure of a growing fish include the following: (1) intense cell proliferation in the filaments and lamellae, resulting in increasing epithelial thickness and decreasing interlamellar distance; (2) pillar cell system atrophy, which reduces the blood circulation through the lamellae; (3) the generation of long cytoplasmic processes from the epithelial cells into the intercellular space, resulting in continuous and sinuous paracellular channels between the epithelial cells of the filament and lamella that may be involved in gas, ion, and nutrient transport to epithelial cells; and (4) intense mitochondria-rich cell (MRC) proliferation in the lamellar epithelium. All of these morphological changes in the gills contribute to a low increase of the respiratory surface area for gas exchange and an increase in the water-blood diffusion distance increasing their dependence on air-breathing as fish developed. The increased proliferation of MRCs may contribute to increased ion uptake, which favors the regulation of ion content and pH equilibrium. PMID:23956000

  15. Protective effect of bone marrow derived mesenchymal stem cells in lipopolysaccharide-induced acute lung injury mediated by claudin-4 in a rat model

    PubMed Central

    Zheng, Yueliang; Cai, Wenwei; Zhou, Shengang; Xu, Liming; Jiang, Chengxing

    2016-01-01

    Our study aims to investigate the effects of bone marrow derived mesenchymal stem cells (BM-MSCs) in lipopolysaccharide (LPS)-induced acute lung injury (ALI) as well as the underlying mechanism. In our study, Wistar rats were randomly divided into four groups: control group; ALI group; ALI+MSCs group and ALI+MSCs claudin-4 siRNA group. MRC-5 and BEAS-2B cell lines were used for in vitro assay. Flow cytometry, western blot, hematoxylin and eosin (H&E) staining, CCK-8 assay, enzyme-linked immunosorbent assay (ELISA) were involved to measure the pathological changes in lung tissues. Results showed that in vivo MSCs administration significantly attenuated pulmonary edema (wet/dry ratio), inflammation cytokines levels (TGF-α), pathological alternations and cell apoptosis which were mediated by claudin-4 in LPS-induced acute lung injury in rats. In vitro experiment showed that hypoxia could induce the expression of claudin-4 in MSCs, and MSCs treatment showed significantly enhanced cell viability (by CCK-8 assay) and reduced cell apoptosis. In conclusion, the present study demonstrated that BM-MSCs can protect against LPS-induced ALI in vivo and in vitro, at least partly mediated by claudin-4. PMID:27725857

  16. Performance improvement of OFDM-FSO multi-user communication system with combined transmit frequency diversity and receive space diversity

    NASA Astrophysics Data System (ADS)

    Kumar, Pravindra; Srivastava, Anand

    2016-05-01

    Orthogonal frequency division multiplexed (OFDM) based free space optical (FSO) communication link gives improved performance because of narrow-band interference, improved robustness against fading and high bandwidth efficiency. It is further improved using transmit frequency diversity and space diversity at the receiver. In this paper, we propose to use OFDM architecture combined with spreading code in electrical domain, referred as code division multiplexed-orthogonal frequency division multiplexing (CDM-OFDM) which provides frequency diversity at the transmitter and using more than one receiver to get receive diversity. Analytical model of CDM-OFDM-FSO communication system with photo-detector space diversity using maximal ratio combining (MRC) is analyzed in the presence of turbulent atmosphere, multi-user-interference (MUI) and timing jitter. The error performance is computed in terms of receiver sensitivity and bit-error-rate (BER). In the analysis, Gamma-Gamma distribution is considered for atmospheric turbulence. The performance of OFDM-FSO link and CDM-OFDM-FSO link is compared. It is seen that for multiple users, CDM-OFDM-FSO link with transmit and receive diversity gives improved performance as compared to OFDM-FSO link.

  17. Code-Time Diversity for Direct Sequence Spread Spectrum Systems

    PubMed Central

    Hassan, A. Y.

    2014-01-01

    Time diversity is achieved in direct sequence spread spectrum by receiving different faded delayed copies of the transmitted symbols from different uncorrelated channel paths when the transmission signal bandwidth is greater than the coherence bandwidth of the channel. In this paper, a new time diversity scheme is proposed for spread spectrum systems. It is called code-time diversity. In this new scheme, N spreading codes are used to transmit one data symbol over N successive symbols interval. The diversity order in the proposed scheme equals to the number of the used spreading codes N multiplied by the number of the uncorrelated paths of the channel L. The paper represents the transmitted signal model. Two demodulators structures will be proposed based on the received signal models from Rayleigh flat and frequency selective fading channels. Probability of error in the proposed diversity scheme is also calculated for the same two fading channels. Finally, simulation results are represented and compared with that of maximal ration combiner (MRC) and multiple-input and multiple-output (MIMO) systems. PMID:24982925

  18. Overloaded Minimum Total Squared Correlation Signatures Based Pilot Aided System for MC-CDMA and STBC MC-CDMA

    NASA Astrophysics Data System (ADS)

    Arifianto, M. S.; Chekima, A.; Hamid, M. Y.; Barukang, L.; Viswacheda, D. V.

    This paper proposes multiple-access schemes based on Overloaded Minimum Total Squared Correlation (TSC) signatures, namely Pilot Aided Multi-Carrier Code-Division Multiple-Access (MC-CDMA) and Pilot Aided Space Time Block Codes (STBC) MC-CDMA. Since overloaded minimum TSC signatures were used as the spreading codes, a number of sub-channels in the MC-CDMA and STBC MC-CDMA schemes were not utilized for data transmission. These empty sub-channels can be exploited for comb-type pilot signaling. To maintain low system complexity, for the pilot sub-channels Least Square (LS) estimation was employed and for interpolating the characteristics of the data sub-channels linear interpolator was applied. The validity of the schemes is confirmed by comparing them with the original MC-CDMA method using Walsh-Hadamard orthogonal codes and also with Walsh-Hadamard based STBC MC-CDMA with block-type pilot. All systems use Equal Gain Combining (EGC) or Maximum Ratio Combining (MRC) in the MC-CDMA block at the receiver. The simulation result shows that although the spreading codes of interest are not fully orthogonal codes, for a low number of users the systems under investigation performed better than their Walsh-Hadamard based counterpart. This will be valuable for Wireless Personal Area Network (PAN) where the number of users is typically low.

  19. Electric Cell-Substrate Impedance Sensing (ECIS) with Microelectrode Arrays for Investigation of Cancer Cell-Fibroblasts Interaction.

    PubMed

    Tran, Trong Binh; Baek, Changyoon; Min, Junhong

    2016-01-01

    The tumor microenvironment, including stromal cells, surrounding blood vessels and extracellular matrix components, has been defined as a crucial factor that influences the proliferation, drug-resistance, invasion and metastasis of malignant epithelial cells. Among other factors, the communications and interaction between cancer cells and stromal cells have been reported to play pivotal roles in cancer promotion and progression. To investigate these relationships, an on-chip co-culture model was developed to study the cellular interaction between A549-human lung carcinoma cells and MRC-5-human lung epithelial cells in both normal proliferation and treatment conditions. In brief, a co-culture device consisting of 2 individual fluidic chambers in parallel, which were separated by a 100 μm fence was utilized for cell patterning. Microelectrodes arrays were installed within each chamber including electrodes at various distances away from the confrontation line for the electrochemical impedimetric sensing assessment of cell-to-cell influence. After the fence was removed and cell-to-cell contact occurred, by evaluating the impedance signal responses representing cell condition and behavior, both direct and indirect cell-to-cell interactions through conditioned media were investigated. The impact of specific distances that lead to different influences of fibroblast cells on cancer cells in the co-culture environment was also defined. PMID:27088611

  20. Interactions among Lung Cancer Cells, Fibroblasts, and Macrophages in 3D Co-Cultures and the Impact on MMP-1 and VEGF Expression.

    PubMed

    Liu, Xiao-Qing; Kiefl, Rosemarie; Roskopf, Claudia; Tian, Fei; Huber, Rudolf M

    2016-01-01

    In vitro cell-based models of lung cancer are frequently employed to study invasion and the mechanisms behind metastasis. However, these models often study only one cell type with two-dimensional (2D) monolayer cell cultures, which do not accurately reflect the complexity of inflammation in vivo. Here, a three-dimensional (3D) cell co-culture collagen gel model was employed, containing human lung adenocarcinoma cells (HCC), human lung fibroblast cells (MRC-5), and macrophages. Cell culture media and cell images were collected, and matrix metalloproteinase-1 (MMP-1) and vascular endothelial growth factor (VEGF) production was monitored under different cell culture conditions. We found that simulating hypoxia and/or serum starvation conditions induced elevated secretion of VEGF in the 3D co-culture model in vitro, but not MMP-1; the morphology of HCC in the 2D versus the 3D co-culture system was extremely different. MMP-1 and VEGF were secreted at higher levels in mixed cell groups rather than mono-culture groups. Therefore, incorporating lung cancer cells, fibroblasts, and macrophages may better reflect physiological metastasis mechanisms compared to mono-culture systems. Tumour stromal cells, macrophages, and fibroblast cells may promote invasion and metastasis, which also provides a new direction for the design of therapies targeted at destroying the stroma of tumor tissues.

  1. VIMOS-VLT and Spitzer observations of a radio galaxy at z= 2.5*

    NASA Astrophysics Data System (ADS)

    Villar-Martín, M.; Sánchez, S. F.; De Breuck, C.; Peletier, R.; Vernet, J.; Rettura, A.; Seymour, N.; Humphrey, A.; Stern, D.; di Serego Alighieri, S.; Fosbury, R.

    2006-02-01

    We present: (i) a kinematic and morphological study of the giant Lyα nebula associated with the radio galaxy MRC 2104-242 (z= 2.49) based on integral field spectroscopic Visible Multiobject Spectrograph (VIMOS) data from the Very Large Telescope (VLT), and (ii) a photometric study of the host (proto?) galaxy based on Spitzer Space Telescope data. The galaxy appears to be embedded in a giant (>~120 kpc) gas reservoir that surrounds it completely. The kinematic properties of the nebula suggest that it is a rotating structure, which would imply a lower limit to the dynamical mass of ~3 × 1011Msolar. An alternate scenario is that the gas is infalling. Such a process would be able to initiate and sustain significant central starburst activity, although it is likely to contribute with less than 10 per cent of the total stellar mass. The near- to mid-infrared spectral energy distribution of the radio galaxy suggests the existence of a reddened, E(B-V) = 0.4 +/- 0.1, evolved stellar population of age >~1.8 Gyr and mass (5 +/- 2) × 1011Msolar. The implied formation redshift is zf>~ 6. This stellar mass is similar to the stellar masses found for massive early-type galaxies at z~ 2 in deep, near-infrared surveys.

  2. Implicit Solvation Parameters Derived from Explicit Water Forces in Large-Scale Molecular Dynamics Simulations

    PubMed Central

    2012-01-01

    Implicit solvation is a mean force approach to model solvent forces acting on a solute molecule. It is frequently used in molecular simulations to reduce the computational cost of solvent treatment. In the first instance, the free energy of solvation and the associated solvent–solute forces can be approximated by a function of the solvent-accessible surface area (SASA) of the solute and differentiated by an atom–specific solvation parameter σiSASA. A procedure for the determination of values for the σiSASA parameters through matching of explicit and implicit solvation forces is proposed. Using the results of Molecular Dynamics simulations of 188 topologically diverse protein structures in water and in implicit solvent, values for the σiSASA parameters for atom types i of the standard amino acids in the GROMOS force field have been determined. A simplified representation based on groups of atom types σgSASA was obtained via partitioning of the atom–type σiSASA distributions by dynamic programming. Three groups of atom types with well separated parameter ranges were obtained, and their performance in implicit versus explicit simulations was assessed. The solvent forces are available at http://mathbio.nimr.mrc.ac.uk/wiki/Solvent_Forces. PMID:23180979

  3. Endo180 at the cutting edge of bone cancer treatment and beyond.

    PubMed

    Sturge, Justin

    2016-03-01

    Skeletal bone is an attractive site for secondary tumour growth and is also home to spontaneous primary cancer. Treatment of bone metastasis is focused on limiting the vicious cycle of bone destruction with bisphosphonates or inhibition of receptor activator of nuclear factor-κB ligand (RANKL) with the fully human monoclonal antibody denosumab. The estimated 1 million deaths/year where bone metastasis is present, and the high healthcare costs required for its management, have ignited intensive research into the cellular and molecular pathology of osteolysis, involving interplay between tumour cells, bone-forming osteoblasts and bone-degrading osteoclasts. Compared to bone metastasis, knowledge about the pathology of primary bone cancers is limited. In recent work published in this journal, Engelholm et al provide a unique insight into how this poorly understood disease manifests and destroys bone. For the first time they have demonstrated that a mouse monoclonal antibody targeting the collagen receptor Endo180 (CD280, MRC2 uPARAP) can prevent osteolysis and bone destruction in a syngeneic model of advanced osteosarcoma. Their convincing findings make an important contribution towards Endo180-based therapy being developed as an option for the treatment of bone cancer amongst other malignancies. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland. PMID:26576691

  4. Stereocontrolled synthesis of the four 16-hydroxymethyl-19-nortestosterone isomers and their antiproliferative activities.

    PubMed

    Schneider, Gyula; Kiss, Anita; Mernyák, Erzsébet; Benke, Zsanett; Wölfling, János; Frank, Éva; Bózsity, Noémi; Gyovai, András; Minorics, Renáta; Zupkó, István

    2016-01-01

    Novel 16-hydroxymethyl-19-nortestosterone diastereomers were prepared by Birch reduction from the corresponding 3-methoxy-16-hydroxymethylestra-1,3,5(10)-trien-17-ol isomers with known configurations. The synthesized compounds are 16α- and 16β-hydroxymethyl-substituted 19-nortestosterone and their 17α-epimers. To prepare 17α-19-nortestosterone, the Mitsunobu inversion reaction of 19-nortestosterone with different alkyl and aryl carboxylic acids was chosen. Deacylation of the new compounds by the Zemplén method yielded the required 17α-19-nortestosterone. The antiproliferative activities of the structurally related compounds were determined in vitro through microculture tetrazolium assays on a panel of human adherent cervical (HeLa, SiHa and C33A), breast (MCF-7, MDA-MB-231, MDA-MB-361 and T47D) and ovarian (A2780) cell lines. The 17α epimer of 19-nortestosterone demonstrated considerable activity, selectively for HeLa cells, with a calculated IC50 of 0.65 μM. The reference compound, cisplatin, displayed an order of magnitude higher IC50 (12.4 μM). The cancer selectivity of 17α-19-nortestosterone was tested by MTT assay performed with noncancerous human fibroblast cell line MRC-5. The results indicated that 17α-19-nortestosterone selectively disturbs the viability of HeLa cells without greatly affecting other cancer cell types and intact fibroblasts. PMID:26686898

  5. Improved survival with the addition of radiotherapy to androgen deprivation: questions answered and a review of current controversies in radiotherapy for non-metastatic prostate cancer

    PubMed Central

    Kavanagh, Brian D.; Rusthoven, Chad G.

    2016-01-01

    The contemporary standard of care for locally advanced high-risk prostate cancer includes a combination of dose-escalated radiotherapy (RT) plus androgen-deprivation therapy (ADT). However, 20 years ago, at the inception of the National Cancer Institute of Canada (NCIC) led study (NCIC Clinical Trials Group PR.3/Medical Research Council PR07/Intergroup T94-0110), the survival impact of prostate RT for high-risk disease was uncertain. Recently, Mason, Warde and colleagues presented the final results of this NCIC/MRC study (PMID: 25691677) randomizing 1,205 high-risk prostate cancer patients to ADT + RT vs. ADT alone. These updated results confirm substantial improvements with the addition of RT to ADT for the endpoints of overall survival (OS), disease-free survival (DFS), and biochemical recurrence. Close examination of subtleties of this trial’s design highlight some of the most salient controversies in the field of prostate RT, including the risk-stratified roles of ADT, optimal ADT duration, and RT field design in the dose-escalated and intensity-modulated radiotherapy (IMRT) era. PMID:26855950

  6. Herpesviruses in Abscesses and Cellulitis of Endodontic Origin

    PubMed Central

    Chen, Vicky; Chen, Yanwen; Li, Hong; Kent, Karla; Baumgartner, J. Craig; Machida, Curtis A.

    2009-01-01

    Acute apical abscesses and cellulitis are severe endodontic diseases caused by opportunistic bacteria with possible co-infection with latent herpesviruses. The objectives of this study are to identify herpesviruses, including human cytomegalovirus (HCMV), Epstein-Barr virus (EBV), herpes simplex virus-1 (HSV-1) and Varicella zoster virus (VZV), in patients (n=31) presenting with acute apical abscesses and cellulitis of endodontic origin. Primary and nested polymerase chain reaction (PCR) was conducted using virus-specific primers and DNA isolated from cell-free abscess fluid. From patients exhibiting concurrent spontaneous pain (n=28), nine abscesses contained HCMV, two abscesses contained EBV, one abscess contained HSV-1, and no abscesses contained VZV. Control PCR using genomic or recombinant templates demonstrated detection limits to a single genomic copy of HCMV, 100 genomic copies for EBV, and 1-10 copies for HSV-1, with no cross-amplification between herpesviral DNA targets. Nested PCR was required for detection of herpesviral DNA in the abscess specimens, indicating that these viruses were present in low copy number. Filtration of abscess specimens and virus transfer experiments using human fibroblastic MRC-5 cells confirmed the presence of HCMV particles in several abscess specimens. We conclude that herpesviruses are present, but not required for development of acute apical abscesses and cellulitis of endodontic origin. PMID:19166769

  7. Exposure to PM10 as a risk factor for