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Sample records for mrc rt01 isrctn47772397

  1. Late Gastrointestinal Toxicity After Dose-Escalated Conformal Radiotherapy for Early Prostate Cancer: Results From the UK Medical Research Council RT01 Trial (ISRCTN47772397)

    SciTech Connect

    Syndikus, Isabel; Morgan, Rachel C.; Sydes, Matthew R.; Graham, John D.; Dearnaley, David P.

    2010-07-01

    Purpose: In men with localized prostate cancer, dose-escalated conformal radiotherapy (CFRT) improves efficacy outcomes at the cost of increased toxicity. We present a detailed analysis to provide further information about the incidence and prevalence of late gastrointestinal side effects. Methods and Materials: The UK Medical Research Council RT01 trial included 843 men with localized prostate cancer, who were treated for 6 months with neoadjuvant radiotherapy and were randomly assigned to either 64-Gy or 74-Gy CFRT. Toxicity was evaluated before CFRT and during long-term follow-up using Radiation Therapy Oncology Group (RTOG) grading, the Late Effects on Normal Tissue: Subjective, Objective, Management (LENT/SOM) scale, and Royal Marsden Hospital assessment scores. Patients regularly completed Functional Assessment of Cancer Therapy--Prostate (FACT-P) and University of California, Los Angeles, Prostate Cancer Index (UCLA-PCI) questionnaires. Results: In the dose-escalated group, the hazard ratio (HR) for rectal bleeding (LENT/SOM grade {>=}2) was 1.55 (95% CI, 1.17-2.04); for diarrhea (LENT/SOM grade {>=}2), the HR was 1.79 (95% CI, 1.10-2.94); and for proctitis (RTOG grade {>=}2), the HR was 1.64 (95% CI, 1.20-2.25). Compared to baseline scores, the prevalence of moderate and severe toxicities generally increased up to 3 years and than lessened. At 5 years, the cumulative incidence of patient-reported severe bowel problems was 6% vs. 8% (standard vs. escalated, respectively) and severe distress was 4% vs. 5%, respectively. Conclusions: There is a statistically significant increased risk of various adverse gastrointestinal events with dose-escalated CFRT. This remains at clinically acceptable levels, and overall prevalence ultimately decreases with duration of follow-up.

  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. Novel MRC algorithms using GPGPU

    NASA Astrophysics Data System (ADS)

    Kato, Kokoro; Taniguchi, Yoshiyuki; Inoue, Tadao; Kadota, Kazuya

    2012-06-01

    GPGPU (General Purpose Graphic Processor Unit) has been attracting many engineers and scientists who develop their own software for massive numerical computation. With hundreds of core-processors and tens of thousands of threads operating concurrently, GPGPU programs can run significantly fast if their software architecture is well optimized. The basic program model used in GPGPU is SIMD (Single Instruction Multiple Data stream), and one must adapt his programming model to SIMD. However, conditional branching is fundamentally not allowed in SIMD and this limitation is quite challenging to apply GPGPU to photomask related software such as MDP or MRC. In this paper unique methods are proposed to utilize GPU for MRC operation. We explain novel algorithms of mask layout verification by GPGPU.

  4. Characterization of SWIR cameras by MRC measurements

    NASA Astrophysics Data System (ADS)

    Gerken, M.; Schlemmer, H.; Haan, Hubertus A.; Siemens, Christofer; Münzberg, M.

    2014-05-01

    Cameras for the SWIR wavelength range are becoming more and more important because of the better observation range for day-light operation under adverse weather conditions (haze, fog, rain). In order to choose the best suitable SWIR camera or to qualify a camera for a given application, characterization of the camera by means of the Minimum Resolvable Contrast MRC concept is favorable as the MRC comprises all relevant properties of the instrument. With the MRC known for a given camera device the achievable observation range can be calculated for every combination of target size, illumination level or weather conditions. MRC measurements in the SWIR wavelength band can be performed widely along the guidelines of the MRC measurements of a visual camera. Typically measurements are performed with a set of resolution targets (e.g. USAF 1951 target) manufactured with different contrast values from 50% down to less than 1%. For a given illumination level the achievable spatial resolution is then measured for each target. The resulting curve is showing the minimum contrast that is necessary to resolve the structure of a target as a function of spatial frequency. To perform MRC measurements for SWIR cameras at first the irradiation parameters have to be given in radiometric instead of photometric units which are limited in their use to the visible range. In order to do so, SWIR illumination levels for typical daylight and twilight conditions have to be defined. At second, a radiation source is necessary with appropriate emission in the SWIR range (e.g. incandescent lamp) and the irradiance has to be measured in W/m2 instead of Lux = Lumen/m2. At third, the contrast values of the targets have to be calibrated newly for the SWIR range because they typically differ from the values determined for the visual range. Measured MRC values of three cameras are compared to the specified performance data of the devices and the results of a multi-band in-house designed Vis-SWIR camera

  5. 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

  6. 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

  7. Reduction of MRC error review time through the simplified and classified MRC result

    NASA Astrophysics Data System (ADS)

    Lee, Casper W.; Lin, Jason C.; Chen, Frank F.

    2009-04-01

    As the Manufacturing Rule Check (MRC) error counts are very huge, it has been getting difficult to review by each point and maybe some of the design errors will be ignored. It's necessary to reduce the review error counts and improve the checking methods. The paper presents an error classification function and auto-waived mechanism for decreasing the repeated MRC errors in MRC report. In auto-waived mechanism, the report will omit the error point if it is same as previous report and the defect location output will keep all of the error points for Do Not Inspection Area (DNIR) reference. (DNIR needs customer's approval). Furthermore, it is possible to develop an auto-waived function to skip the confirmed errors which is provided by customer with a marking information table or GDS/OASIS database. Besides, this paper also presents how these errors can be grouping and reducing checking time.

  8. Mask manufacturing rules checking (MRC) as a DFM strategy

    NASA Astrophysics Data System (ADS)

    Buck, Peter; Gladhill, Richard; Straub, Joseph

    2007-03-01

    Mask Manufacturing Rules Checking (MRC) has been established as an automated process to detect mask pattern data that will cause mask inspection problems. This methodology is unique from the Design Rule Checking (DRC) or Design for Manufacturing (DFM) checks typically performed before sending pattern data to the mask manufacturer in that it examines the entire mask layout and the spatial relationship between multiple patterns in their final orientation, scale, and tone. In contrast, DRC and DFM checks are usually performed on individual pattern files. Also, DRC and DFM checks are not always performed after all pattern transformations are complete, and errors can be introduced that are not caught until the mask is eventually printed on wafers. Therefore, MRC can often be the only comprehensive geometric integrity test performed before the mask is manufactured and the last opportunity to catch critical errors that might have disastrous consequences to yield and consequently to product schedules. In this paper we review the concepts and implementation of MRC in a merchant mask manufacturing enterprise and introduce methods to empower DFM decisions by mask customers based on MRC results.

  9. 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.

  10. The MRC dyspnoea scale by telephone interview to monitor health status in elderly COPD patients.

    PubMed

    Paladini, Luciana; Hodder, Rick; Cecchini, Isabella; Bellia, Vincenzo; Incalzi, Raffaele Antonelli

    2010-07-01

    Dyspnoea is the most common symptom associated with poor quality of life in patients affected by Chronic Obstructive Pulmonary Disease (COPD). While COPD severity is commonly staged by lung function, the Medical Research Council (MRC) dyspnoea scale has been proposed as a more clinically meaningful method of quantifying disease severity in COPD. We wished to assess whether this scale might also be useful during telephone surveys as a simple surrogate marker of perceived health status in elderly patients with COPD. We conducted a comprehensive health status assessment by telephone survey of 200 elderly patients who had a physician diagnosis of COPD. The telephone survey contained 71 items and explored such domains as educational level, financial status, living arrangements and social contacts, co-morbid illness, and the severity and the impact of COPD on health status. Patients were categorized according to the reported MRC score: mild dyspnoea (MRC scale of 1), moderate dyspnoea (MRC scale of 2 and 3), or severe dyspnoea (MRC of 4 and 5). Deterioration in most of the recorded indicators of health status correlated with an increasingly severe MRC score. This was most evident for instrumental activities of daily living (IADL), perceived health and emotional status, pain-related limitations, limitations in social life, hospital admissions in preceding year and prevalence of most co-morbidities. The MRC dyspnoea scale is a reliable index of disease severity and health status in elderly COPD patients which should prove useful for remote monitoring of COPD and for rating health status for epidemiological purposes. PMID:20116231

  11. Experimental research on the MRC diversity reception algorithm for UV communication.

    PubMed

    Guo, Li; Meng, Dedan; Liu, Kunlun; Mu, Xidong; Feng, Weilun; Han, Dahai

    2015-06-01

    Ultraviolet (UV) communication is an emerging communication method with non-line-of-sight, anti-interference, and anti-interception capabilities, along with high flexibility and reliability. Herein, the maximum ratio combining (MRC) diversity reception algorithm for a UV communication system is studied. Simulation and experimental results indicate that single and multiple outputs are useful and achievable, with an obvious diversity gain, and the MRC diversity reception algorithm can reduce the system bit error rate more effectively than the equal-gain combining method. The simulation and experimental results are analyzed, and the differences between them are discussed. These results provide guidelines for UV communication system design and implementation. PMID:26192664

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

    PubMed Central

    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. PMID:26201080

  13. Features of COPD patients by comparing CAT with mMRC: a retrospective, cross-sectional study

    PubMed Central

    Huang, Wei-Chang; Wu, Ming-Feng; Chen, Hui-Chen; Hsu, Jeng-Yuan

    2015-01-01

    Background: The group assignment of chronic obstructive pulmonary disease (COPD) may differ depending on whether the COPD assessment test (CAT) or modified Medical Research Council dyspnoea scale (mMRC) is used. Aims: This study intended to clarify how different patient characteristics influence the differences, to determine the relationships between CAT and mMRC and to characterise COPD patients by both CAT and mMRC. Methods: This was a retrospective, cross-sectional study. The data, collected by Taiwan Obstructive Lung Disease consortium, were managed and analysed. Results: Of the 757 participants, COPD group assignment was not identical as well as no substantial agreement presented when categorised based on the cut-point CAT score ⩾10 and each mMRC cut-point. In all, 38.2% of participants had discordant group assignments together with a lower mean CAT score, less severe airway obstruction and less severe airflow limitation compared with those with concordant group assignments. In the discordant group, the CAT⩾10/mMRC 0–1 subgroup had more wheezing than CAT<10/mMRC⩾2 subgroup. Only moderate correlations existed between CAT and mMRC. More-symptom groups and combined high-risk group had better correlations than less-symptom groups and combined low-risk group, respectively. A modest negative correlation existed between forced expiratory volume in 1 s percentage (FEV1%) predicted and CAT score and between FEV1% predicted and mMRC scale in parallel with a significant positive relationship existing between the CAT score and mMRC scale. Notably, a significant proportion of COPD patients with each scale of mMRC had health status impairment. Conclusions: The Global initiative for Chronic Obstructive Lung Disease committee should redefine the applications of CAT and mMRC in the management of COPD. PMID:26538368

  14. 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

  15. Simulation study of the dynamic performance of a MRC plant with refrigerant charged or leaked

    NASA Astrophysics Data System (ADS)

    Sun, Heng; Shu, Dan; Jiang, Zhihua

    2012-01-01

    The running condition of a MRC plant is affected by the charge or leakage of the refrigerant. It is significant for the design and operation of the plant. A new model which is established based on the process simulation, mass conservation and characteristics of the system was employed to study the dynamic performance in these cases. The results show that the light composition mainly affects the pressure and the heavy composition affects the liquid level of vessel more obviously. This is due to the fact that the light composition mainly stays in the vapor phase and the heavies stay in the liquid phase mostly. The case when leakages occur at different location was also studied. The results can provide useful information for the adjustment of mixture refrigerant and operation of a MRC plant.

  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. PMID:27071802

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

    PubMed

    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 AND 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

  19. Cadmium-induced oxidative cellular damage in human fetal lung fibroblasts (MRC-5 cells).

    PubMed Central

    Yang, C F; Shen, H M; Shen, Y; Zhuang, Z X; Ong, C N

    1997-01-01

    Epidemiological evidence suggests that cadmium (Cd) exposure causes pulmonary damage such as emphysema and lung cancer. However, relatively little is known about the mechanisms involved in Cd pulmonary toxicity. In the present study, the effects of Cd exposure on human fetal lung fibroblasts (MRC-5 cells) were evaluated by determination of lipid peroxidation, intra-cellular production of reactive oxygen species (ROS), and changes of mitochondrial membrane potential. A time- and dose-dependent increase of both lactate dehydrogenase leakage and malondialdehyde formation was observed in Cd-treated cells. A close correlation between these two events suggests that lipid peroxidation may be one of the main pathways causing its cytotoxicity. It was also noted that Cd-induced cell injury and lipid peroxidation were inhibited by catalase and superoxide dismutase, two antioxidant enzymes. By using the fluorescent probe 2',7'-dichlorofluorescin diacetate, a significant increase of ROS production in Cd-treated MRC-5 cells was detected. The inhibition of dichlorofluorescein fluorescence by catalase, not superoxide dismutase, suggests that hydrogen peroxide is the main ROS involved. Moreover, the significant dose-dependent changes of mitochondrial membrane potential in Cd-treated MRC-5 cells, demonstrated by increased fluorescence of rhodamine 123 examined using a laser-scanning confocal microscope, also indicate the involvement of mitochondrial damage in Cd cytotoxicity. These findings provide in vitro evidence that Cd causes oxidative cellular damage in human fetal lung fibroblasts, which may be closely associated with the pulmonary toxicity of Cd. Images Figure 1. A Figure 1. B Figure 2. A Figure 2. B Figure 3. A Figure 3. B Figure 4. A Figure 4. B Figure 5. Figure 6. Figure 7. A Figure 7. B PMID:9294717

  20. 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

  1. 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

  2. Mrc1 and Srs2 are major actors in the regulation of spontaneous crossover

    PubMed Central

    Robert, Thomas; Dervins, Delphine; Fabre, Francis; Gangloff, Serge

    2006-01-01

    In vegetative cells, most recombination intermediates are metabolized without an association with a crossover (CO). The avoidance of COs allows for repair and prevents genomic rearrangements, potentially deleterious if the sequences involved are at ectopic locations. We have designed a system that permits to screen spontaneous intragenic recombination events in Saccharomyces cerevisiae and to investigate the CO outcome in different genetic contexts. We have analyzed the CO outcome in the absence of the Srs2 and Sgs1 helicases, DNA damage checkpoint proteins as well as in a mutant proliferating cell nuclear antigen (PCNA) and found that they all contribute to genome stability. Remarkably high effects on COs are mediated by srs2Δ, mrc1Δ and a pol30-RR mutation in PCNA. Our results support the view that Mrc1 plays a specific role in DNA replication, promoting the Srs2 recruitment to PCNA independently of checkpoint signaling. Srs2 would prevent formation of double Holliday junctions (dHJs) and thus CO formation. Sgs1 also negatively regulates CO formation but through a different process that resolves dHJs to yield non-CO products. PMID:16724109

  3. Adhesion of MRC-5 and A549 cells on poly(dimethylsiloxane) surface modified by proteins.

    PubMed

    Zuchowska, Agnieszka; Kwiatkowski, Piotr; Jastrzebska, Elzbieta; Chudy, Michal; Dybko, Artur; Brzozka, Zbigniew

    2016-02-01

    PDMS is a very popular material used for fabrication of Lab-on-a-Chip systems for biological applications. Although PDMS has numerous advantages, it is a highly hydrophobic material, which inhibits adhesion and proliferation of the cells. PDMS surface modifications are used to enrich growth of the cells. However, due to the fact that each cell type has specific adhesion, it is necessary to optimize the parameters of these modifications. In this paper, we present an investigation of normal (MRC-5) and carcinoma (A549) human lung cell adhesion and proliferation on modified PDMS surfaces. We have chosen these cell types because often they are used as models for basic cancer research. To the best of our knowledge, this is the first presentation of this type of investigation. The combination of a gas-phase processing (oxygen plasma or ultraviolet irradiation) and wet chemical methods based on proteins' adsorption was used in our experiments. Different proteins such as poly-l-lysine, fibronectin, laminin, gelatin, and collagen were incubated with the activated PDMS samples. To compare with other works, here, we also examined how ratio of prepolymer to curing agent (5:1, 10:1, and 20:1) influences PDMS hydrophilicity during further modifications. The highest adhesion of the tested cells was observed for the usage of collagen, regardless of PDMS ratio. However, the MRC-5 cell line demonstrated better adhesion than A549 cells. This is probably due to the difference in their morphology and type (normal/cancer). PMID:26311334

  4. Role of protein kinase C-η in cigarette smoke extract-induced apoptosis in MRC-5-cells.

    PubMed

    Son, E S; Kyung, S Y; Lee, S P; Jeong, S H; Shin, J Y; Ohba, M; Yeo, E J; Park, J W

    2015-09-01

    Cigarette smoke (CS) is a major risk factor for emphysema, which causes cell death in structural cells of the lung by mechanisms that are still not completely understood. We demonstrated previously that CS extract (CSE) induces caspase activation in MRC-5 human lung fibroblasts, activated protein kinase C-η (PKC-η), and translocated PKC-η from the cytosol to the membrane. The objective of this study was to investigate the involvement of PKC-η activation in a CSE-induced extrinsic apoptotic pathway. We determined that CSE increases expression of caspase 3 and 8 cleavage in MRC-5 cells and overexpression of PKC-η significantly increased expression of caspase 3 and 8 cleavage compared with control LacZ-infected cells. In contrast, dominant negative (dn) PKC-η inhibited apoptosis in MRC-5 cells exposed to CSE and decreased expression of caspase 3 and 8 compared with control cells. Exposure to 10% CSE for >8 h significantly increased lactate dehydrogenase release in PKC-η-infected cells compared with LacZ-infected cells. Additionally, PKC-η-infected cells had an increased number of Hoechst 33342 stained nuclei compared with LacZ-infected cells, while dn PKC-η-infected cells exhibited fewer morphological changes than LacZ-infected cells under phase-contrast microscopy. In conclusion, PKC-η activation plays a pro-apoptotic role in CSE-induced extrinsic apoptotic pathway in MRC-5 cells. These results suggest that modulation of PKC-η may be a useful tool for regulating the extrinsic apoptosis of MRC-5 cells by CSE and may have therapeutic potential in the treatment of CS-induced lung injury. PMID:25504686

  5. 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.

  6. 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.

  7. 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

  8. The mysterious morphology of MRC0943-242 as revealed by ALMA and MUSE

    NASA Astrophysics Data System (ADS)

    Gullberg, Bitten; De Breuck, Carlos; Lehnert, Matthew D.; Vernet, Joël; Bacon, Roland; Drouart, Guillaume; Emonts, Bjorn; Galametz, Audrey; Ivison, Rob; Nesvadba, Nicole P. H.; Richard, Johan; Seymour, Nick; Stern, Daniel; Wylezalek, Dominika

    2016-02-01

    We present a pilot study of the z = 2.923 radio galaxy MRC0943-242, where we combine information from ALMA and MUSE data cubes for the first time. Even with modest integration times, we disentangle the AGN and starburst dominated components. These data reveal a highly complex morphology as the AGN, starburst, and molecular gas components show up as widely separated sources in dust continuum, optical continuum, and CO line emission observations. CO(1-0) and CO(8-7) line emission suggest that there is a molecular gas reservoir offset from both the dust and the optical continuum that is located ~90 kpc from the AGN. The UV line emission has a complex structure in emission and absorption. The line emission is mostly due to a large scale ionisation cone energised by the AGN, and a Lyα emitting bridge of gas between the radio galaxy and a heavily star-forming set of components. Strangely, the ionisation cone has no Lyα emission. We find this is due to an optically thick layer of neutral gas with unity covering fraction spread out over a region of at least ~100 kpc from the AGN. Other less thick absorption components are associated with Lyα emitting gas within a few tens of kpc from the radio galaxy and are connected by a bridge of emission. We speculate that this linear structure of dust, Lyα and CO emission, and the redshifted absorption seen in the circum nuclear region may represent an accretion flow feeding gas into this massive AGN host galaxy.

  9. 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

  10. 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

  11. SER performance of enhanced spatial multiplexing codes with ZF/MRC receiver in time-varying Rayleigh fading channels.

    PubMed

    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. Extracellular Caspase-8 Dependent Apoptosis on HeLa Cancer Cells and MRC-5 Normal Cells by ICD-85 (Venom Derived Peptides)

    PubMed Central

    Zare-Mirakabadi, Abbas; Sarzaeem, Ali

    2012-01-01

    Background Our previous studies revealed an inhibitory effect of ICD-85 (venom derived peptides) on MDA-MB231 and HL-60 cell lines, through induction of apoptosis. The purpose of this study was to investigate apoptosis-induced mechanism on HeLa and MRC-5 cells by ICD-85 through activation of caspase-8. Methods Cell viability, cytosolic enzyme Lactate Dehydrogenase (LDH) and cell morphology were assessed under unexposed and ICD-85 exposed conditions.Caspase-8 activity was assayed by caspase-8 colorimetric assay Kit. Results The results show that Inhibitory Concentration 50% (IC50) value of ICD-85 for HeLa cells at 24 h was estimated and found to be 25.32±2.15 µg/mL. Furthermore, treatment of HeLa cells with ICD-85 at concentrations of 1.6×10 and 2.6×10 µg/mL did not significantly increase LDH release. Morphological changes in HeLa cells on treatment with ICD-85 compared with untreated HeLa cells consistent with an apoptotic mechanism of cell death, such as cell shrinkage which finally results in the generation of apoptotic bodies. However, when MRC-5 cells were exposed to ICD-85, no significant changes in cell morphology and LDH were observed at concentrations below 2.6×10µg/ml. Also, the apoptosis-induction mechanism by ICD-85 on HeLa cells was found through activation of caspase-8 and the activity of caspase-8 in HeLa cells was 1.5 folds more than its activity on MRC-5 cells. Conclusion Therefore, the apoptosis-induced mechanisms by ICD-85 are through activation of caspase-8 and concerning the least cytotoxic effect on MRC-5 cells, ICD-85 may be used as anticancer compound to inhibit growth of cancer cells. PMID:25352970

  13. 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.

  14. 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.

  15. The extended ionized gas around the z = 2.44 radio galaxy MRC 0406-244: the nature of the superbubbles and the optical line brightness asymmetries

    NASA Astrophysics Data System (ADS)

    Humphrey, A.; Iwamuro, F.; Villar-Martín, M.; Binette, L.; Sung, E. C.

    2009-10-01

    In this Letter, we investigate the nature of the dramatic `superbubble' emission structures associated with the z = 2.44 radio galaxy MRC 0406-244, using rest-frame optical spectroscopy and an archival Hubble Space Telescope (HST) Near-Infrared Camera and Multi-Object Spectrometer (NICMOS) image. Based on the optical line ratios and the HST morphology, we conclude that the gas in the superbubbles is photoionized by the obscured active nucleus. We suggest that this type of structure might be related to the spatially extended HI absorbers that are detected in front of many high-z radio galaxies. We also suggest that we may be witnessing the destruction of the extended emission-line region. In addition, we investigate the nature of the emission-line brightness asymmetry in MRC 0406-244: we conclude that this asymmetry is due to an asymmetry in the mass of ionized gas, confirming the scenario of McCarthy, van Breugel & Kapahi, and leading us to reject that of Gopal-Krishna & Wiita.

  16. 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

  17. 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

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

    2009-09-01

    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

  18. Assessing the survival of MRC5 and a549 cell lines upon exposure to pyruvic Acid, sodium citrate and sodium bicarbonate - biomed 2013.

    PubMed

    Farah, Ibrahim O; Lewis, Veshell L; Ayensu, Wellington K; Cameron, Joseph A

    2013-01-01

    Lung cancer is among the most prevalent and deadly cancers in United States. In general, cancer cells are known to exhibit higher rates of glycolysis in comparison to normal cells. In attempting to exploit this unique cancer-dependent ATP generation phenomenon, it was our hypothesis that upon exposure to organic inhibitors of glycolysis, cancer cells would not survive normally and that their growth and viability would be vastly decreased; essential glycolytic ATP production will be exhausted to the point of collapsing energy utilization. Furthermore, we hypothesize that no negative effect would be seen with exposures to organic inhibitors for normal lung cells. The human lung fibroblast MRC-5 and the human A549 alveolar epithelial cell lines were used as in vitro models of normal lung and lung cancers respectively. Using standard methods, both cell lines were maintained and exposed to pyruvic acid, sodium citrate and sodium bicarbonate reagents at concentration levels ranging from 31.3-2,000 µg/ml in 96 well plates in quadruplets and experiments repeated at least three times using MTT, and cell counting (T4 Cellometer) assays as well as phase-contrast photo-imaging for parallel morphological displays of any changes in the course of their vitality and metabolic activities. Our results indicate that exposure of both cell lines to these organics resulted in concentration dependent cell destruction/cell survival depending on the cell line exposed. Pyruvic acid, sodium citrate and sodium bicarbonate showed statistically significant (p<0.05) differential negative effects on the A549 cell line in comparison to its unexposed control as well as to their effects on the MRC-5 cell line, presenting a potential promise for their use as cancer biotherapeutics. PMID:23686189

  19. 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

  20. 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

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

    PubMed Central

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

    2016-01-01

    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

  2. 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

  3. Addition of cetuximab to oxaliplatin-based first-line combination chemotherapy for treatment of advanced colorectal cancer: results of the randomised phase 3 MRC COIN trial

    PubMed Central

    Maughan, Timothy S; Adams, Richard A; Smith, Christopher G; Meade, Angela M; Seymour, Matthew T; Wilson, Richard H; Idziaszczyk, Shelley; Harris, Rebecca; Fisher, David; Kenny, Sarah L; Kay, Edward; Mitchell, Jenna K; Madi, Ayman; Jasani, Bharat; James, Michelle D; Bridgewater, John; Kennedy, M John; Claes, Bart; Lambrechts, Diether; Kaplan, Richard; Cheadle, Jeremy P

    2011-01-01

    Summary Background In the Medical Research Council (MRC) COIN trial, the epidermal growth factor receptor (EGFR)-targeted antibody cetuximab was added to standard chemotherapy in first-line treatment of advanced colorectal cancer with the aim of assessing effect on overall survival. Methods In this randomised controlled trial, patients who were fit for but had not received previous chemotherapy for advanced colorectal cancer were randomly assigned to oxaliplatin and fluoropyrimidine chemotherapy (arm A), the same combination plus cetuximab (arm B), or intermittent chemotherapy (arm C). The choice of fluoropyrimidine therapy (capecitabine or infused fluouroracil plus leucovorin) was decided before randomisation. Randomisation was done centrally (via telephone) by the MRC Clinical Trials Unit using minimisation. Treatment allocation was not masked. The comparison of arms A and C is described in a companion paper. Here, we present the comparison of arm A and B, for which the primary outcome was overall survival in patients with KRAS wild-type tumours. Analysis was by intention to treat. Further analyses with respect to NRAS, BRAF, and EGFR status were done. The trial is registered, ISRCTN27286448. Findings 1630 patients were randomly assigned to treatment groups (815 to standard therapy and 815 to addition of cetuximab). Tumour samples from 1316 (81%) patients were used for somatic molecular analyses; 565 (43%) had KRAS mutations. In patients with KRAS wild-type tumours (arm A, n=367; arm B, n=362), overall survival did not differ between treatment groups (median survival 17·9 months [IQR 10·3–29·2] in the control group vs 17·0 months [9·4–30·1] in the cetuximab group; HR 1·04, 95% CI 0·87–1·23, p=0·67). Similarly, there was no effect on progression-free survival (8·6 months [IQR 5·0–12·5] in the control group vs 8·6 months [5·1–13·8] in the cetuximab group; HR 0·96, 0·82–1·12, p=0·60). Overall response rate increased from 57% (n=209

  4. An Overdensity of Massive, Dusty Starbursts Associated with the High-Redshift Radio Galaxy MRC1138-262 at z = 2.16

    NASA Astrophysics Data System (ADS)

    Altieri, Bruno; Dannerbauer, Helmut

    We present Herschel and APEX LABOCA 870 μm imaging of the field of the high-redshift radio galaxy MRC1138 at z = 2.16. We detect 16 submillimeter galaxies in this ˜140 arcmin2 large bolometer map, with flux densities in the range 3-11 mJy. The pure number counts indicate an overdensity of SMGs by a factor of five compared to blank field surveys. Based on an exquisite multi-wavelength database including VLA 1.4 GHz radio and infrared observations, we verifiy whether these sources are members of the proto-cluster structure at z = 2.2 or not. Based on Herschel PACS+ SPIRE and Spitzer MIPS photometry, we derived reliable far-infrared photometric redshifts for all of our sources. VLT-ISAAC near-infrared spectroscopic observations confirmed redshifts of z ≈ 2.2 for four of these SMGs. We conclude that in total at least seven sources are part of this proto-cluster at z = 2.16. We measure a star formation rate density S FRD ˜ 1500 M⊙ yr-1 Mpc-3, four magntiudes higher compared to the global SFRD at this redshift. Striklingly, these seven sources are concentrated within a region of 2 Mpc (the typical size of clusters in the local universe) and are not distributed in the filaments as predicted by theories and traced by the Hα emitters at z ≈ 2.2. This concentration of massive, dusty starbursts is not centered on the radio galaxy which is submm bright. A significant fraction, six out of 11 SMGs with z ≈ 2.2 Hα imaging coverage are associated with Hα emitters, demonstrating the potential of tracing SMG counterparts with this source population. Our results demonstrate that indeed submm observations enable us to reveal clusters of massive, dusty starbursts and will pave the road for systematic and detailed investigations with this technique in the future.

  5. 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

  6. Association between resting heart rate across the life course and all-cause mortality: longitudinal findings from the Medical Research Council (MRC) National Survey of Health and Development (NSHD)

    PubMed Central

    Hartaigh, Bríain Ó; Gill, Thomas M; Shah, Imran; Hughes, Alun D; Deanfield, John E; Kuh, Diana; Hardy, Rebecca

    2014-01-01

    Background Resting heart rate (RHR) is an independent risk factor for mortality. Nevertheless, it is unclear whether elevations in childhood and mid-adulthood RHR, including changes over time, are associated with mortality later in life. We sought to evaluate the association between RHR across the life course, along with its changes and all-cause mortality. Methods We studied 4638 men and women from the Medical Research Council (MRC) National Survey of Health and Development (NSHD) cohort born during 1 week in 1946. RHR was obtained during childhood at ages 6, 7 and 11, and in mid-adulthood at ages 36 and 43. Using multivariable Cox regression, we calculated the HR for incident mortality according to RHR measured at each time point, along with changes in mid-adulthood RHR. Results At age 11, those in the top fifth of the RHR distribution (≥97 bpm) had an increased adjusted hazard of 1.42 (95% CI 1.04 to 1.93) for all-cause mortality. A higher adjusted risk (HR, 95% CI 2.17, 1.40 to 3.36) of death was also observed for those in the highest fifth (≥81 bpm) at age 43. For a > 25 bpm increased change in the RHR over the course of 7 years (age 36–43), the adjusted hazard was elevated more than threefold (HR, 95% CI 3.26, 1.54 to 6.90). After adjustment, RHR at ages 6, 7 and 36 were not associated with all-cause mortality. Conclusions Elevated RHR during childhood and midlife, along with greater changes in mid-adulthood RHR, are associated with an increased risk of all-cause mortality. PMID:24850484

  7. 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

  8. 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

  9. Bacterial actin: architecture of the ParMRC plasmid DNA partitioning complex.

    PubMed

    Salje, Jeanne; Löwe, Jan

    2008-08-20

    The R1 plasmid employs ATP-driven polymerisation of the actin-like protein ParM to move newly replicated DNA to opposite poles of a bacterial cell. This process is essential for ensuring accurate segregation of the low-copy number plasmid and is the best characterised example of DNA partitioning in prokaryotes. In vivo, ParM only forms long filaments when capped at both ends by attachment to a centromere-like region parC, through a small DNA-binding protein ParR. Here, we present biochemical and electron microscopy data leading to a model for the mechanism by which ParR-parC complexes bind and stabilise elongating ParM filaments. We propose that the open ring formed by oligomeric ParR dimers with parC DNA wrapped around acts as a rigid clamp, which holds the end of elongating ParM filaments while allowing entry of new ATP-bound monomers. We propose a processive mechanism by which cycles of ATP hydrolysis in polymerising ParM drives movement of ParR-bound parC DNA. Importantly, our model predicts that each pair of plasmids will be driven apart in the cell by just a single double helical ParM filament. PMID:18650930

  10. Portable RF leak detector evaluations and UDRI/MRC HAMS refinements

    NASA Astrophysics Data System (ADS)

    Schafer, David A.; Chapman, Gerald P.; Finci, Aka G.

    1992-07-01

    Two tasks related to the detection and measurement of EMI/RFI leaks in electrically shielded portable tactical shelters were carried out. The first task consisted of the evaluation of four portable, hand-held radio frequency (RF) leak detectors ('sniffers'). The evaluation consisted of an assessment of their reliability, ease of operation, battery life, and sensitivity. Their performance was measured on an S25OG tactical shelter and compared against MIL-STD-285 test results. The second task consisted of the refinement of a previously developed hardness assurance monitoring system (HAMS). These refinements included further development of the sensor-driven pairs by which EMI leaks are detected and identification of commercial replacement components for custom-built parts in the original prototype unit. This is the first step towards militarization of the design.

  11. 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

  12. 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

  13. 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

  14. Oxidized LDL induces an oxidative stress and activates the tumor suppressor p53 in MRC5 human fibroblasts.

    PubMed

    Mazière, C; Meignotte, A; Dantin, F; Conte, M A; Mazière, J C

    2000-09-24

    It is now well established that oxidized LDL (OxLDL) is involved in the progression of the atheromatous plaque via several mechanisms, including its cytotoxicity toward the arterial wall. Our study demonstrates that a 4-h incubation of cultured human fibroblasts with 25-75 microg/ml OxLDL induced a dose-dependent increase in the intracellular levels of reactive oxygen species (ROS) and lipid peroxidation end products (TBARS). This effect was markedly prevented by the antioxidant vitamin E. The lipid extract of OxLDL partially reproduced the action of the LDL particle itself. Concomitantly, OxLDL enhanced the DNA binding activity of p53 measured by electrophoretic mobility shift assay, and the intracellular protein level of p53 determined by immunoblot analysis. Cycloheximide prevented the OxLDL-induced augmentation in both p53 binding activity and intracellular level. Again, the lipid extract of OxLDL reproduced the effect of OxLDL on p53 binding activity, whereas vitamin E prevented it. These results indicate that OxLDL initiates an intracellular oxidative stress by means of its lipid peroxidation products, leading to the activation of the tumour suppressor p53 by enhancement of p53 protein synthesis. This effect might be related to the cytotoxic effect of OxLDL since the activation of p53 is known to lead to cell cycle arrest, necrosis or apoptosis. PMID:11027537

  15. Multi-Hop Link Capacity of Multi-Route Multi-Hop MRC Diversity for a Virtual Cellular Network

    NASA Astrophysics Data System (ADS)

    Daou, Imane; Kudoh, Eisuke; Adachi, Fumiyuki

    In virtual cellular network (VCN), proposed for high-speed mobile communications, the signal transmitted from a mobile terminal is received by some wireless ports distributed in each virtual cell and relayed to the central port that acts as a gateway to the core network. In this paper, we apply the multi-route MHMRC diversity in order to decrease the transmit power and increase the multi-hop link capacity. The transmit power, the interference power and the link capacity are evaluated for DS-CDMA multi-hop VCN by computer simulation. The multi-route MHMRC diversity can be applied to not only DS-CDMA but also other access schemes (i. e. MC-CDMA, OFDM, etc.).

  16. Nephroblastoma: treatment during 1970-3 and the effect on survival of inclusion in the first MRC trial.

    PubMed Central

    Lennox, E L; Stiller, C A; Jones, P H; Wilson, L M

    1979-01-01

    In 1970-3 313 children were diagnosed as having nephroblastoma in Great Britain. From the start of the first Medical Research Council nephroblastoma study in October 1970 until the end of 1973, 98 children (57% of all eligible children) were included in the trial. Of the 313 children, 288 (92%) had a nephrectomy, 248 (79%) received a course of radiotherapy, and 267 (85%) were given at least four days' chemotherapy. The three-year survival rate was 58%; the rate among children in the trial (77%) was significantly better than that among children who were eligible for the trial but not included (58%). Children who had nephrectomies at specialised children's and teaching hospitals had a higher survival rate than those treated elsewhere. All children with nephroblastoma should be treated according to well-defined protocols which take into account the age of the child and the stage of the tumour and include a full course of maintenance chemotherapy. PMID:227525

  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. An Integrational Model of Quality of Life in Older Age. Results from the Esrc/mrc Hsrc Quality of Life Survey in Britain.(author Abstract)

    ERIC Educational Resources Information Center

    Bowling, Ann; Gabriel, Zahava

    2004-01-01

    This paper is based on the results of a national survey of the quality of life of 999 randomly sampled people aged 65 and over, living at home in Britain. The survey was semi-structured, and a sample of survey respondents was followed up and interviewed in-depth in order to explore their perceptions of quality of life in full. Comparisons are made…

  19. 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

  20. Assignment of the human macrophage mannose receptor gene (MRC1) to 10p13 by in situ hybridization and PCR-based somatic cell hybrid mapping

    SciTech Connect

    Eichbaum, Q.; Clerc, P.; Bruns, G.

    1994-08-01

    Tissue macrophages form a latticework beneath epithelial surfaces and play a pivotal role in first line host defense. The macrophage mannose receptor is highly expressed on these terminally differentiated cells, but is not expressed on circulating monocytes. Although originally defined as an endocytic receptor, the predominant physiological role for this 170-kDa transmembrane protein appears to be phagocytosis of microorganisms, such as Candida albicans and Pneumocystis carinii. The characterization of cDNAs that encode the human and mouse mannose receptors reveals that the ectodomain contains a cysteine-rich NH{sub 2} domain that appears to resemble the b subunit of ricin D. This domain is followed by a fibronectin type 2 domain. A tandem array of eight carbohydrate recognition domains bear approximately 30% homology to one another. A short hydrophobic region is followed by a 45-amino-acid cytoplasmic tail. Comparison of the human and mouse encoded proteins reveals an average homology of 80%. Of interest is the fact that the murine and human genes both span about 70 kb that contains 30 exons interrupted by 29 introns. The position of the introns and the size of the exons are identical in the mouse and human genes. 15 refs., 2 figs.

  1. 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

  2. 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

  3. Thioguanine used in maintenance therapy of chronic myeloid leukaemia causes non-cirrhotic portal hypertension. Results from MRC CML. II. Trial comparing busulphan with busulphan and thioguanine.

    PubMed

    Shepherd, P C; Fooks, J; Gray, R; Allan, N C

    1991-10-01

    Portal hypertension with varices developed in 18/675 patients with chronic myeloid leukaemia (CML) in a randomized trial comparing busulphan with busulphan and thioguanine. All 18 had received the drug combination and none busulphan alone (P less than 0.0001). Ascites was also seen significantly more often in the combination arm (P less than 0.05). These results strongly suggest that the addition of thioguanine was responsible for the development of portal hypertension. The histological features were predominantly those of non-cirrhotic portal hypertension--either idiopathic portal hypertension with minimal morphological abnormalities, nodular regenerative hyperplasia or in two cases leukaemic infiltration only was noted. Cirrhosis was present in 3/16 cases studied. Both treatment groups developed abnormal liver function tests during the chronic phase, but particularly with progression of the disease. During chronic phase abnormalities were significantly more frequent in those receiving busulphan and thioguanine-alkaline phosphatase (P less than 0.02), transaminases (P less than 0.04), bilirubin (P less than 0.05), multiple abnormalities (P less than 0.01). The development of portal hypertension was often associated with abnormalities of these tests; however, lack of specificity precludes their use as a predictor of subsequent clinical problems. Thioguanine confers no survival advantage in this disease. In view of its hepatotoxicity it should not be used routinely for maintenance of control in chronic phase CML. PMID:1958475

  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. Chemotherapy options in elderly and frail patients with metastatic colorectal cancer (MRC FOCUS2): an open-label, randomised factorial trial

    PubMed Central

    Seymour, Matthew T; Thompson, Lindsay C; Wasan, Harpreet S; Middleton, Gary; Brewster, Alison E; Shepherd, Stephen F; O'Mahony, M Sinead; Maughan, Timothy S; Parmar, Mahesh; Langley, Ruth E

    2011-01-01

    Summary Background Elderly and frail patients with cancer, although often treated with chemotherapy, are under-represented in clinical trials. We designed FOCUS2 to investigate reduced-dose chemotherapy options and to seek objective predictors of outcome in frail patients with advanced colorectal cancer. Methods We undertook an open, 2 × 2 factorial trial in 61 UK centres for patients with previously untreated advanced colorectal cancer who were considered unfit for full-dose chemotherapy. After comprehensive health assessment (CHA), patients were randomly assigned by minimisation to: 48-h intravenous fluorouracil with levofolinate (group A); oxaliplatin and fluorouracil (group B); capecitabine (group C); or oxaliplatin and capecitabine (group D). Treatment allocation was not masked. Starting doses were 80% of standard doses, with discretionary escalation to full dose after 6 weeks. The two primary outcome measures were: addition of oxaliplatin ([A vs B] + [C vs D]), assessed with progression-free survival (PFS); and substitution of fluorouracil with capecitabine ([A vs C] + [B vs D]), assessed by change from baseline to 12 weeks in global quality of life (QoL). Analysis was by intention to treat. Baseline clinical and CHA data were modelled against outcomes with a novel composite measure, overall treatment utility (OTU). This study is registered, number ISRCTN21221452. Findings 459 patients were randomly assigned (115 to each of groups A–C, 114 to group D). Factorial comparison of addition of oxaliplatin versus no addition suggested some improvement in PFS, but the finding was not significant (median 5·8 months [IQR 3·3–7·5] vs 4·5 months [2·8–6·4]; hazard ratio 0·84, 95% CI 0·69–1·01, p=0·07). Replacement of fluorouracil with capecitabine did not improve global QoL: 69 of 124 (56%) patients receiving fluorouracil reported improvement in global QoL compared with 69 of 123 (56%) receiving capecitabine. The risk of having any grade 3 or worse toxic effect was not significantly increased with oxaliplatin (83/219 [38%] vs 70/221 [32%]; p=0·17), but was higher with capecitabine than with fluorouracil (88/222 [40%] vs 65/218 [30%]; p=0·03). In multivariable analysis, fewer baseline symptoms (odds ratio 1·32, 95% CI 1·14–1·52), less widespread disease (1·51, 1·05–2·19), and use of oxaliplatin (0·57, 0·39–0·82) were predictive of better OTU. Interpretation FOCUS2 shows that with an appropriate design, including reduced starting doses of chemotherapy, frail and elderly patients can participate in a randomised controlled trial. On balance, a combination including oxaliplatin was preferable to single-agent fluoropyrimidines, although the primary endpoint of PFS was not met. Capecitabine did not improve QoL compared with fluorouracil. Comprehensive baseline assessment holds promise as an objective predictor of treatment benefit. Funding Cancer Research UK and the Medical Research Council. PMID:21570111

  7. The effect of interleukin-1 receptor antagonist therapy on markers of inflammation in non-ST elevation acute coronary syndromes: the MRC-ILA Heart Study

    PubMed Central

    Morton, Allison C.; Rothman, Alexander M. K.; Greenwood, John P.; Gunn, Julian; Chase, Alex; Clarke, Bernard; Hall, Alistair S.; Fox, Keith; Foley, Claire; Banya, Winston; Wang, Duolao; Flather, Marcus D.; Crossman, David C.

    2015-01-01

    Aims Acute coronary syndromes (ACSs) are driven by inflammation within coronary plaque. Interleukin-1 (IL-1) has an established role in atherogenesis and the vessel-response to injury. ACS patients have raised serum markers of inflammation. We hypothesized that if IL-1 is a driving influence of inflammation in non-ST elevation ACS (NSTE-ACS), IL-1 inhibition would reduce the inflammatory response at the time of ACS. Methods and results A phase II, double-blinded, randomized, placebo-controlled, study recruited 182 patients with NSTE-ACS, presenting <48 h from onset of chest pain. Treatment was 1:1 allocation to daily, subcutaneous IL-1receptor antagonist (IL-1ra) or placebo for 14 days. Baseline characteristics were well matched. Treatment compliance was 85% at 7 days. The primary endpoint (area-under-the-curve for C-reactive protein over the first 7 days) was: IL-1ra group, 21.98 mg day/L (95%CI 16.31–29.64); placebo group, 43.5 mg day/L (31.15–60.75) (geometric mean ratio = 0.51 mg/L; 95%CI 0.32–0.79; P = 0.0028). In the IL-1ra group, 14-day achieved high-sensitive C-reactive protein (P < 0.0001) and IL-6 levels (P = 0.02) were lower than Day 1. Sixteen days after discontinuation of treatment (Day 30) high-sensitive C-reactive protein levels had risen again in the IL-1ra group [IL-1ra; 3.50 mg/L (2.65–4.62): placebo; 2.21 mg/L (1.67–2.92), P = 0.022]. MACE at Day 30 and 3 months was similar but at 1 year there was a significant excess of events in the IL-1ra group. Conclusion IL-1 drives C-reactive protein elevation at the time of NSTE-ACS. Following 14 days IL-1ra treatment inflammatory markers were reduced. These results show the importance of IL-1 as a target in ACS, but also indicate the need for additional studies with anti-IL-1 therapy in ACS to assess duration and safety. Clinical Trial Registration EUCTR: 2006-001767-31-GB: www.clinicaltrialsregister.eu/ctr-search/trial/2006-001767-31/GB. PMID:25079365

  8. Phenolic Profiling of Duchesnea indica Combining Macroporous Resin Chromatography (MRC) with HPLC-ESI-MS/MS and ESI-IT-MS.

    PubMed

    Zhu, Mingzhi; Dong, Xia; Guo, Mingquan

    2015-01-01

    Duchesnea indica (D. indica) is an important traditional Chinese medicine, and has long been clinically used to treat cancer in Asian countries. It has been described previously as a rich source of phenolic compounds with a broad array of diversified structures, which are the major active ingredients. However, an accurate and complete phenolic profiling has not been determined yet. In the present work, the total phenolic compounds in crude extracts from D. indica were enriched and fractionated over a macroporous resin column, then identified by HPLC-ESI-MS/MS and ESI-IT-MS (ion trap MS). A total of 27 phenolic compounds were identified in D. indica, of which 21 compounds were identified for the first time. These 27 phenolic compounds encompassing four phenolic groups, including ellagitannins, ellagic acid and ellagic acid glycosides, hydroxybenzoic acid and hydroxycinnamic acid derivatives, and flavonols, were then successfully quantified using peak areas against those of the corresponding standards with good linearity (R² > 0.998) in the range of the tested concentrations. As a result, the contents of individual phenolic compounds varied from 6.69 mg per 100 g dry weight (DW) for ellagic acid to 71.36 mg per 100 g DW for brevifolin carboxylate. Not only did this study provide the first phenolic profiling of D. indica, but both the qualitative identification and the subsequent quantitative analysis of 27 phenolic compounds from D. indica should provide a good basis for future exploration of this valuable medicinal plant. PMID:26694333

  9. A randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced transitional cell carcinoma: results and a report on prognostic factors in a Medical Research Council study. MRC Advanced Bladder Cancer Working Party.

    PubMed Central

    Mead, G. M.; Russell, M.; Clark, P.; Harland, S. J.; Harper, P. G.; Cowan, R.; Roberts, J. T.; Uscinska, B. M.; Griffiths, G. O.; Parmar, M. K.

    1998-01-01

    Transitional cell carcinomas may arise at any site within the urinary tract and are a source of considerable morbidity and mortality. In particular, patients with metastatic disease have a poor prognosis, with less than 5% alive at 5 years. A multicentre randomized trial comparing methotrexate and vinblastine (MV) with cisplatin, methotrexate and vinblastine (CMV) in advanced or metastatic transitional cell carcinoma was conducted in the UK. From April 1991 to June 1995, 214 patients were entered by 16 centres, 108 randomized to CMV and 106 to MV. A total of 204 patients have died. The hazard ratio (relative risk of dying) was 0.68 (95% CI 0.51-0.90, P-value = 0.0065) in favour of CMV. This translates to an absolute improvement in 1-year survival of 13%, 16% in MV and 29% in CMV. The median survival for CMV and MV was 7 months and 4.5 months respectively. Two hundred and eight patients objectively progressed or died. The hazard ratio was 0.55 (95% CI 0.41-0.73, P-value = 0.0001) in favour of CMV. Two hundred and nine patients symptomatically progressed or died. The hazard ratio was 0.48 (95% CI 0.36-0.64, P-value = 0.0001) in favour of CMV. The most important pretreatment factors influencing overall survival were WHO performance status and extent of disease. These two factors were used to derive a prognostic index which could be used to categorize patients into three prognostic groups. We conclude that the addition of cisplatin to methotrexate and vinblastine should be considered in patients with transitional cell carcinoma, taking into account the increased toxicity. PMID:9792152

  10. Associations of behavioural risk factors and health status with changes in physical capability over 10 years of follow-up: the MRC National Survey of Health and Development

    PubMed Central

    Cooper, Rachel; Muniz-Terrera, Graciela; Kuh, Diana

    2016-01-01

    Objectives (1) To describe changes in objective measures of physical capability between ages 53 and 60–64 years; (2) to investigate the associations of behavioural risk factors (obesity, physical inactivity, smoking) and number of health conditions (range 0–4: hand osteoarthritis (OA); knee OA; severe respiratory symptoms; other disabling or life-threatening conditions (ie, cancer, cardiovascular disease, diabetes)) at age 53 years with these changes. Design Nationally representative prospective birth cohort study. Setting England, Scotland and Wales. Participants Up to 2093 men and women from the Medical Research Council National Survey of Health and Development, who have been followed-up since birth in 1946, and underwent physical capability assessments performed by nurses following standard protocols in 1999 and 2006–2010. Main outcome measures Grip strength and chair rise speed were assessed at ages 53 and 60–64 years. Four categories of change in grip strength and chair rise speed were identified: decline, stable high, stable low, a reference group who maintained physical capability within a ‘normal’ range. Results Less healthy behavioural risk scores and an increase in the number of health conditions experienced were associated in a stepwise fashion with increased risk of decline in physical capability, and also of having low levels at baseline and remaining low. For example, the sex and mutually adjusted relative-risk ratios (95% CI) of being in the stable low versus reference category of chair rise speed were 1.58 (1.35–1.86) and 1.97 (1.57–2.47) per 1 unit change in behavioural risk score and health indicator count, respectively. Conclusions These findings provide evidence of the associations of a range of modifiable factors with age-related changes in physical capability. They suggest the need to target multiple risk factors at least as early as mid-life when aiming to promote maintenance and prevent decline in physical capability in later life. PMID:27091818

  11. 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…

  12. 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

  13. Mannose Receptor 2 Attenuates Renal Fibrosis

    PubMed Central

    López-Guisa, Jesús M.; Cai, Xiaohe; Collins, Sarah J.; Yamaguchi, Ikuyo; Okamura, Daryl M.; Bugge, Thomas H.; Isacke, Clare M.; Emson, Claire L.; Turner, Scott M.; Shankland, Stuart J.

    2012-01-01

    Mannose receptor 2 (Mrc2) expresses an extracellular fibronectin type II domain that binds to and internalizes collagen, suggesting that it may play a role in modulating renal fibrosis. Here, we found that Mrc2 levels were very low in normal kidneys but subsets of interstitial myofibroblasts and macrophages upregulated Mrc2 after unilateral ureteral obstruction (UUO). Renal fibrosis and renal parenchymal damage were significantly worse in Mrc2-deficient mice. Similarly, Mrc2-deficient Col4α3−/− mice with hereditary nephritis had significantly higher levels of total kidney collagen, serum BUN, and urinary protein than Mrc2-sufficient Col4α3−/− mice. The more severe phenotype seemed to be the result of reduced collagen turnover, because procollagen III (α1) mRNA levels and fractional collagen synthesis in the wild-type and Mrc2-deficient kidneys were similar after UUO. Although Mrc2 associates with the urokinase receptor, differences in renal urokinase activity did not account for the increased fibrosis in the Mrc2-deficient mice. Treating wild-type mice with a cathepsin inhibitor, which blocks proteases implicated in Mrc2-mediated collagen degradation, worsened UUO-induced renal fibrosis. Cathepsin mRNA profiles were similar in Mrc2-positive fibroblasts and macrophages, and Mrc2 genotype did not alter relative cathepsin mRNA levels. Taken together, these data establish an important fibrosis-attenuating role for Mrc2-expressing renal interstitial cells and suggest the involvement of a lysosomal collagen turnover pathway. PMID:22095946

  14. 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

  15. Correlating carbon monoxide oxidation with cox genes in the abundant Marine Roseobacter Clade

    PubMed Central

    Cunliffe, Michael

    2011-01-01

    The Marine Roseobacter Clade (MRC) is a numerically and biogeochemically significant component of the bacterioplankton. Annotation of multiple MRC genomes has revealed that an abundance of carbon monoxide dehydrogenase (CODH) cox genes are present, subsequently implying a role for the MRC in marine CO cycling. The cox genes fall into two distinct forms based on sequence analysis of the coxL gene; forms I and II. The two forms are unevenly distributed across the MRC genomes. Most (18/29) of the MRC genomes contain only the putative form II coxL gene. Only 10 of the 29 MRC genomes analysed have both the putative form II and the definitive form I coxL. None have only the form I coxL. Genes previously shown to be required for post-translational maturation of the form I CODH enzyme are absent from the MRC genomes containing only form II. Subsequent analyses of a subset of nine MRC strains revealed that only MRC strains with both coxL forms are able to oxidise CO. PMID:21068776

  16. 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.

  17. 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 &...

  18. 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...

  19. 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

  20. 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…

  1. 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.…

  2. Children With Intracranial Arachnoid Cysts: Classification and Treatment.

    PubMed

    Tan, Zhen; Li, Yongxin; Zhu, Fengjun; Zang, Dongdong; Zhao, Cailei; Li, Cong; Tong, Dan; Zhang, Heye; Chen, Qian

    2015-11-01

    We performed a dynamic study of arachnoid cysts (ACs) using magnetic resonance cisternography (MRC) and proposed a classification of ACs.Twenty-three suitable patients in our hospital entered into this study according to our inclusion criteria. MRC images were collected in all the subjects at 1 and 24 hours after the administration of intrathecal gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA). We allocate the enrolled patients into 2 groups, MRC group and surgery group. The MRC results were considered before treatment in 1 group (MRC group, 13 patients), whereas another group was surgically treated without considering the MRC results (surgery group, 10 patients). We calculated the enhanced area of cyst using modified MacDonald Criteria from the images and measured the surrounding subarachnoid area as the reference.We found that it was practically useful to quantify 3 types of ACs, complete communicating, incomplete communicating, and noncommunicating, according to MRC results in this study. All the subjects in both groups are closely observed before the treatment and the follow-up using the MRI examination. In the surgery group, 5 patients were found that the area of cysts shrank in the follow-up stage. However, there was no significant difference in the percentage shrinkage area between the 2 groups.We concluded that MRC with Gd-DTPA as a contrast agent is of significant clinical value for the diagnosis and treatment of children with intracranial ACs. This classification based on dynamic MRC is useful for making surgical recommendations. PMID:26554773

  3. Children With Intracranial Arachnoid Cysts

    PubMed Central

    Tan, Zhen; Li, Yongxin; Zhu, Fengjun; Zang, Dongdong; Zhao, Cailei; Li, Cong; Tong, Dan; Zhang, Heye; Chen, Qian

    2015-01-01

    Abstract We performed a dynamic study of arachnoid cysts (ACs) using magnetic resonance cisternography (MRC) and proposed a classification of ACs. Twenty-three suitable patients in our hospital entered into this study according to our inclusion criteria. MRC images were collected in all the subjects at 1 and 24 hours after the administration of intrathecal gadolinium-diethylenetriamine penta-acetic acid (Gd-DTPA). We allocate the enrolled patients into 2 groups, MRC group and surgery group. The MRC results were considered before treatment in 1 group (MRC group, 13 patients), whereas another group was surgically treated without considering the MRC results (surgery group, 10 patients). We calculated the enhanced area of cyst using modified MacDonald Criteria from the images and measured the surrounding subarachnoid area as the reference. We found that it was practically useful to quantify 3 types of ACs, complete communicating, incomplete communicating, and noncommunicating, according to MRC results in this study. All the subjects in both groups are closely observed before the treatment and the follow-up using the MRI examination. In the surgery group, 5 patients were found that the area of cysts shrank in the follow-up stage. However, there was no significant difference in the percentage shrinkage area between the 2 groups. We concluded that MRC with Gd-DTPA as a contrast agent is of significant clinical value for the diagnosis and treatment of children with intracranial ACs. This classification based on dynamic MRC is useful for making surgical recommendations. PMID:26554773

  4. Iterative Decoding of SPC Outer Coded Concatenation Codes with Maximal Ratio Combining

    NASA Astrophysics Data System (ADS)

    Chen, Xiaogang; Yang, Hongwen

    This letter proposes a simple iterative decoding algorithm for the concatenation codes where the outer code is single-parity-check (SPC) code. The erroneous inner codewords are iteratively combined with maximum ratio combining (MRC) and then re-decoded. Compared with the conventional scheme where the RS outer code concatenation is algebraically decoded to recover the erasures, the proposed scheme has better performance due to MRC processing. On the other hand, the proposed scheme is less complex because the linear combination is simpler than algebraical decoding and the MRC gain can loose the requirement for inner decoder.

  5. Allelic heterogeneity of Crooked Tail Syndrome: result of balancing selection?

    PubMed

    Sartelet, A; Klingbeil, P; Franklin, C K; Fasquelle, C; Géron, S; Isacke, C M; Georges, M; Charlier, C

    2012-10-01

    We report the identification of a second loss-of-function mutation (c.1906T>C) in the bovine MRC2 gene causing the Crooked Tail Syndrome in Belgian Blue Cattle. We demonstrate that the ensuing substitution of the highly conserved Cysteine 636 with Arginine causes illegitimate receptor oligomerization, which is predicted to impair function of the MRC2 encoded protein, Endo180. We propose that this second MRC2 mutation was selected by breeders as a result of its favourable effect on muscularity in heterozygotes. PMID:22497452

  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. Building for the future

    PubMed Central

    2013-01-01

    As the staff of the MRC Laboratory of Molecular Biology settle into their new building in Cambridge, its director Hugh Pelham explains the challenges of living up to its prestigious past. PMID:23741620

  8. Outage Performance and Average Symbol Error Rate of M-QAM for Maximum Ratio Combining with Multiple Interferers

    NASA Astrophysics Data System (ADS)

    Ahn, Kyung Seung

    In this paper, we investigate the performance of maximum ratio combining (MRC) in the presence of multiple cochannel interferences over a flat Rayleigh fading channel. Closed-form expressions of signal-to-interference-plus-noise ratio (SINK), outage probability, and average symbol error rate (SER) of quadrature amplitude modulation (QAM) with Mary signaling are obtained for unequal-power interference-to-noise ratio (INR). We also provide an upper-bound for the average SER using moment generating function (MGF) of the SINR. Moreover, we quantify the array gain loss between pure MRC (MRC system in the absence of CCI) and MRC system in the presence of CCI. Finally, we verify our analytical results by numerical simulations.

  9. Magnetic resonance cholangiography in the assessment and management of biliary complications after OLT

    PubMed Central

    Girometti, Rossano; Cereser, Lorenzo; Bazzocchi, Massimo; Zuiani, Chiara

    2014-01-01

    Despite advances in patient and graft management, biliary complications (BC) still represent a challenge both in the early and delayed period after orthotopic liver transplantation (OLT). Because of unspecific clinical presentation, imaging is often mandatory in order to diagnose BC. Among imaging modalities, magnetic resonance cholangiography (MRC) has gained widespread acceptance as a tool to represent the reconstructed biliary tree noninvasively, using both the conventional technique (based on heavily T2-weighted sequences) and contrast-enhanced MRC (based on the acquisition of T1-weighted sequences after the administration of hepatobiliary contrast agents). On this basis, MRC is generally indicated to: (1) avoid unnecessary procedures of direct cholangiography in patients with a negative examination and/or identify alternative complications; and (2) provide a road map for interventional procedures or surgery. As illustrated in the review, MRC is accurate in the diagnosis of different types of biliary complications, including anastomotic strictures, non-anastomotic strictures, leakage and stones. PMID:25071883

  10. Treatment strategy and long-term results in paediatric patients treated in consecutive UK AML trials.

    PubMed

    Gibson, B E S; Wheatley, K; Hann, I M; Stevens, R F; Webb, D; Hills, R K; De Graaf, S S N; Harrison, C J

    2005-12-01

    Between 1988 and 2002, 758 children with acute myeloid leukaemia (AML) were treated on Medical Research Council (MRC) AML 10 and AML 12. MRC AML 10 tested the role of bone marrow transplantation following four blocks of intensive chemotherapy and found that while both allogeneic bone marrow transplant (allo-BMT) and autologous bone marrow transplant (A-BMT) significantly reduced the relapse risk (RR), this did not translate into a significant improvement in overall survival (OS). A risk group stratification based on cytogenetics and response to the first course of chemotherapy derived from MRC AML 10 was used to deliver risk-directed therapy in MRC AML 12. Allo-BMT was limited to standard and poor risk patients and A-BMT was not employed. Instead, the benefit of an additional block of treatment was tested by randomising children to receive either four or five blocks of treatment in total. While the results of MRC AML 12 remain immature, there appears to be no survival advantage for a fifth course of treatment. The 5 year OS, disease-free survival (DFS), event-free survival (EFS) and RR in MRC AML 12 are 66, 61, 56 and 35%, respectively; at present superior to MRC AML 10, which had a 5-year OS, DFS, EFS and RR of 58, 53, 49 and 42%, respectively. MRC AML trials employ a short course of triple intrathecal chemotherapy alone for CNS-directed treatment and CNS relapse is uncommon. Improvements in supportive care have contributed to improved outcomes and the number of deaths in remission fell between trials. Anthracycline-related cardiotoxicity remains a concern and the current MRC AML 15 trial tests the feasibility of reducing anthracycline dosage without compromising outcome by comparing standard MRC anthracycline-based consolidation with high-dose ara-C. MRC studies suggest that the role of allo-BMT is limited in 1st CR and that there may be a ceiling of benefit from current or conventional chemotherapy. PMID:16304572

  11. 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

  12. Replisome stalling and stabilization at CGG repeats, which are responsible for chromosomal fragility.

    PubMed

    Voineagu, Irina; Surka, Christine F; Shishkin, Alexander A; Krasilnikova, Maria M; Mirkin, Sergei M

    2009-02-01

    Expanded CGG repeats cause chromosomal fragility and hereditary neurological disorders in humans. Replication forks stall at CGG repeats in a length-dependent manner in primate cells and in yeast. Saccharomyces cerevisiae proteins Tof1 and Mrc1 facilitate replication fork progression through CGG repeats. Remarkably, the fork-stabilizing role of Mrc1 does not involve its checkpoint function. Thus, chromosomal fragility might occur when forks stalled at expanded CGG repeats escape the S-phase checkpoint. PMID:19136957

  13. Replisome stalling and stabilization at CGG repeats that are responsible for chromosomal fragility

    PubMed Central

    Voineagu, Irina; Surka, Christine F.; Shishkin, Alexander A.; Krasilnikova, Maria M.; Mirkin, Sergei M.

    2010-01-01

    Expanded CGG repeats cause chromosomal fragility and hereditary neurological disorders in humans. Replication forks stall at CGG repeats in a length-dependent manner in primate cells and in yeast. Yeast Tof1 and Mrc1 proteins facilitate replication fork progression through CGG repeats. Remarkably, the fork-stabilizing role of Mrc1 does not involve its checkpoint function. Thus, chromosomal fragility might occur when forks stalled at expanded CGG repeats escape the S-phase checkpoint. PMID:19136957

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

    PubMed

    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

  15. The Applicability of Intraoperative Neuromonitoring in Patients with Preoperative Motor Weakness during Spine Surgery

    PubMed Central

    Lee, Jae Meen; Kim, Dong Hwan; Kim, Hwan Soo; Choi, Byung Kwan

    2016-01-01

    Objective The purpose of our study is to evaluate the success rate and feasibility of intraoperative neuromonitoring (IONM) focusing on transcranial motor evoked potential (TcMEP) monitoring for patients with preoperative motor weakness in spine surgery. Methods Between November 2011 and December 2013, TcMEP and somatosensory evoked potential (SSEP) monitoring were attempted in 130 consecutive patients undergoing spine surgeries for cervical or thoracic cord lesions. Patients ranged in age from 14 to 81 years (mean±standard deviation, 56.7±14.8 years), and 84 patients were male. The success rates of both SSEP and MEPs monitoring were assessed according to the preoperative Medical Research Council (MRC) and Nurick grades. Results TcMEP was recorded successfully in 0%, 28.6%, 72.3%, and 100% of patients with MRC grades 1, 2, 3, 4, and 5, respectively. SSEP was obtained from 0%, 37.5%, 21.5%, 61.4%, and 85.4% of patients with MRC grades 1, 2, 3, 4, and 5, respectively. TcMEP was recorded successfully in 84% of patients with Nurick grades 1-3 and 26% of patients with Nurick grades 4-5. SSEPs were recorded successfully in 76.3% of patients with Nurick grades 1-3 and 24% of patients with grades 4-5. Conclusion IONM during spine surgery may be useless in patients with MRC grades 1-2, applicable MRC grade 3, and useful MRC grades 4-5. MRC grade 3 is a critical point of indication for application of MEPs. In unmonitorable cases with MRC grade 3, increasing stimulus intensity or facilitation techniques may be considered to improve the usefulness of TcMEP. PMID:27123024

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

    PubMed

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

    2016-07-15

    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

  17. 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.

  18. 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

  19. Menadione-resistant Chinese hamster ovary cells have an increased capacity for glutathione synthesis.

    PubMed Central

    Vallis, K. A.; Reglinski, J.; Garner, M.; Bridgeman, M. M.; Wolf, C. R.

    1997-01-01

    A cell line (MRc40) resistant to the model quinone compound, menadione, has been isolated from a parental Chinese hamster ovary cell line (CHO-K1). The known relationship between menadione toxicity and glutathione (GSH) depletion led us to investigate whether the mechanism of resistance of MRc40 was related to alteration in GSH homeostasis. Intracellular concentrations of GSH and cysteine (CySH) were twofold and 3.2-fold greater in MRc40 than in CHO-K1. Following exposure to menadione, GSH and CySH were depleted, but subsequent recovery of thiols was more rapid and of greater magnitude in MRc40 than in CHO-K1. Twelve hours after exposure to menadione, the concentrations of GSH and CySH were 9.7- and 4.2-fold greater in MRc40 than in CHO-K1. Using nuclear magnetic resonance (NMR) spectroscopy, we observed the in situ removal of menadione from cell suspensions of CHO-K1 and MRc40. However, only in CHO-K1 did we observe concomitant depletion of NMR-visible GSH. We conclude that the perturbation of GSH metabolism contributes to the resistant phenotype and is an important characteristic of menadione-resistant CHO cells. PMID:9328145

  20. 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. PMID:23936009

  1. Modified Medical Research Council scale vs Baseline Dyspnea Index to evaluate dyspnea in chronic obstructive pulmonary disease

    PubMed Central

    Perez, Thierry; Burgel, Pierre Régis; Paillasseur, Jean-Louis; Caillaud, Denis; Deslée, Gaetan; Chanez, Pascal; Roche, Nicolas

    2015-01-01

    Background Assessment of dyspnea in COPD patients relies in clinical practice on the modified Medical Research Council (mMRC) scale, whereas the Baseline Dyspnea Index (BDI) is mainly used in clinical trials. Little is known on the correspondence between the two methods. Methods Cross-sectional analysis was carried out on data from the French COPD cohort Initiatives BPCO. Dyspnea was assessed by the mMRC scale and the BDI. Spirometry, plethysmography, Hospital Anxiety-Depression Scale, St George’s Respiratory Questionnaire, exacerbation rates, and physician-diagnosed comorbidities were obtained. Correlations between mMRC and BDI scores were assessed using Spearman’s correlation coefficient. An ordinal response model was used to examine the contribution of clinical data and lung function parameters to mMRC and BDI scores. Results Data are given as median (interquartile ranges, [IQR]). Two-hundred thirty-nine COPD subjects were analyzed (men 78%, age 65.0 years [57.0; 73.0], forced expiratory volume in 1 second [FEV1] 48% predicted [34; 67]). The mMRC grade and BDI score were, respectively, 1 [1–3] and 6 [4–8]. Both BDI and mMRC scores were significantly correlated at the group level (rho =−0.67; P<0.0001), but analysis of individual data revealed a large scatter of BDI scores for any given mMRC grade. In multivariate analysis, both mMRC grade and BDI score were independently associated with lower FEV1% pred, higher exacerbation rate, obesity, depression, heart failure, and hyperinflation, as assessed by the inspiratory capacity/total lung capacity ratio. The mMRC dyspnea grade was also associated with the thromboembolic history and low body mass index. Conclusion Dyspnea is a complex symptom with multiple determinants in COPD patients. Although related to similar factors (including hyperinflation, depression, and heart failure), BDI and mMRC scores likely explore differently the dyspnea intensity in COPD patients and are clearly not interchangeable. PMID

  2. Dissection of Two Complex Clusters of Resistance Genes in Lettuce (Lactuca sativa).

    PubMed

    Christopoulou, Marilena; McHale, Leah K; Kozik, Alex; Reyes-Chin Wo, Sebastian; Wroblewski, Tadeusz; Michelmore, Richard W

    2015-07-01

    Of the over 50 phenotypic resistance genes mapped in lettuce, 25 colocalize to three major resistance clusters (MRC) on chromosomes 1, 2, and 4. Similarly, the majority of candidate resistance genes encoding nucleotide binding-leucine rich repeat (NLR) proteins genetically colocalize with phenotypic resistance loci. MRC1 and MRC4 span over 66 and 63 Mb containing 84 and 21 NLR-encoding genes, respectively, as well as 765 and 627 genes that are not related to NLR genes. Forward and reverse genetic approaches were applied to dissect MRC1 and MRC4. Transgenic lines exhibiting silencing were selected using silencing of β-glucuronidase as a reporter. Silencing of two of five NLR-encoding gene families resulted in abrogation of nine of 14 tested resistance phenotypes mapping to these two regions. At MRC1, members of the coiled coil-NLR-encoding RGC1 gene family were implicated in host and nonhost resistance through requirement for Dm5/8- and Dm45-mediated resistance to downy mildew caused by Bremia lactucae as well as the hypersensitive response to effectors AvrB, AvrRpm1, and AvrRpt2 of the nonpathogen Pseudomonas syringae. At MRC4, RGC12 family members, which encode toll interleukin receptor-NLR proteins, were implicated in Dm4-, Dm7-, Dm11-, and Dm44-mediated resistance to B. lactucae. Lesions were identified in the sequence of a candidate gene within dm7 loss-of-resistance mutant lines, confirming that RGC12G confers Dm7. PMID:25650829

  3. Diagnostic accuracy of cone-beam CT compared with panoramic images in predicting retromolar canal during extraction of impacted mandibular third molars

    PubMed Central

    Sisman, Yıldıray; Payveren-Arıkan, Mehtap; Sahman, Halil

    2015-01-01

    Objectives: The clinical significance of the existence of a retromolar canal and of its neurovascular content is not yet clear.The aim of the present study was to assess the visibility, diameter and course of the mandibular retromolarcanal (MRC) using cone beam computed tomography (CBCT) scan -had been taken for pre-operative radiographic evaluation of impacted mandibular third molars- compared to panoramic radiographs. Study Design: Subjects eligible for study enrollment were those who underwent preoperative CBCT scan for the extraction of impactedmandibular third molars were determined to be extremely close to the mandibular canal on panoramic radiographs. Radiographs were screened for the presence and course of retromolar canals, and linear measurements. Results: 947hemimandibles in 632 patients were examined.A total of 253 MRCs (144 left, 109 right) were detected with CBCT images (26.7%). Only 29 of these canals were also seen on the corresponding panoramic radiographs. Most MRCs had a vertical course (type VI, 28.46%), followed by slightly curved (type I, 26.09%). The visibility of the MRC on the OPGs, according to the increase in the diameter, was not statistically significant for both sides (p>.05).Statistically difference were found for the width at the point of origin from the mandibular canal (p: .037), the mean distance from the MRC to the second molar (p: .042) and height of MRC when compared the gender. Conclusions: The findings suggest that the MRC isn’t a rare anatomical structure. This study therefore clearly establishes the incidence and importance of the MRC. The detection of the presence of the MRC using CBCT may be crucial for extraction of mandibular third molars. Key words:Accessory innervation, cone beam computed tomography, mandibular anatomy, panoramic radiographs, retromolar canal, retromolar foramen. PMID:25475767

  4. 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

  5. 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

  6. 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

  7. 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.

  8. 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

  9. 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

  10. [Multilocular renal cyst in adults: a diagnosis by exclusion?].

    PubMed

    Redondo Martínez, E; Rey López, A

    1991-05-01

    The clinical and the gross and microscopic features of two multicystic masses in adult female patients are described. These met the Powell and Boggs and Kimelstiel criteria for multilocular renal cyst (MRC). MRC may be the common process and the gross expression of different disease entities with different biological significance which must be distinguished clinically and anatomopathologically. We present the data for differential diagnosis of conditions that may present as MRC: partially differentiated cystic nephroblastoma, mesoblastic congenital cystic nephroma, lymphangioma (more common in infants), cystic renal carcinoma and sarcoma, segmental polycystic kidney (more common in adults) and segmental renal dysplasia. The diagnosis of multilocular renal cyst should be made only after discarding the foregoing conditions. PMID:2064438

  11. Rapid detection of herpes simplex virus with fluorescein-labeled Helix pomatia lectin.

    PubMed Central

    Slifkin, M; Cumbie, R

    1989-01-01

    The use of fluorescein-conjugated Helix pomatia lectin was shown to be as effective as fluorescein-conjugated monoclonal antibody reagents for the detection and differentiation of herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) in MRC-5 cell culture. Cells infected with HSV-1 generally displayed a pattern of nongranular or diffuse fluorescence, while cells infected with HSV-2 were identified by the production of fluorescent grains and flecks. This unique nonimmunological reagent, when used in combination with low-speed centrifugation, provides a remarkably specific, sensitive, rapid, and cost-effective means to detect HSV-infected MRC-5 or BHK-21 cells as early as 20 h postinoculation. In contrast to the immunofluorescence method, the serotypes of HSV can be differentiated with only one fluorescein-H. pomatia reagent in MRC-5 cell cultures. Images PMID:2545739

  12. 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

  13. 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.

  14. Structural Analysis of Mitochondrial Mutations Reveals a Role for Bigenomic Protein Interactions in Human Disease

    PubMed Central

    Lloyd, Rhiannon E.; McGeehan, John E.

    2013-01-01

    Mitochondria are the energy producing organelles of the cell, and mutations within their genome can cause numerous and often severe human diseases. At the heart of every mitochondrion is a set of five large multi-protein machines collectively known as the mitochondrial respiratory chain (MRC). This cellular machinery is central to several processes important for maintaining homeostasis within cells, including the production of ATP. The MRC is unique due to the bigenomic origin of its interacting proteins, which are encoded in the nucleus and mitochondria. It is this, in combination with the sheer number of protein-protein interactions that occur both within and between the MRC complexes, which makes the prediction of function and pathological outcome from primary sequence mutation data extremely challenging. Here we demonstrate how 3D structural analysis can be employed to predict the functional importance of mutations in mtDNA protein-coding genes. We mined the MITOMAP database and, utilizing the latest structural data, classified mutation sites based on their location within the MRC complexes III and IV. Using this approach, four structural classes of mutation were identified, including one underexplored class that interferes with nuclear-mitochondrial protein interactions. We demonstrate that this class currently eludes existing predictive approaches that do not take into account the quaternary structural organization inherent within and between the MRC complexes. The systematic and detailed structural analysis of disease-associated mutations in the mitochondrial Complex III and IV genes significantly enhances the predictive power of existing approaches and our understanding of how such mutations contribute to various pathologies. Given the general lack of any successful therapeutic approaches for disorders of the MRC, these findings may inform the development of new diagnostic and prognostic biomarkers, as well as new drugs and targets for gene therapy. PMID

  15. 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

  16. Effective conflict resolution strategies for SRAF placement

    NASA Astrophysics Data System (ADS)

    Ganjugunte, Shashidhara K.; Strecker, Norbert; Jayaram, Srividya; LaCour, Pat; Torunoglu, Ilhami

    2015-07-01

    Sub-Resolution Assist Features (SRAFs) have emerged as a key technology to enable semiconductor manufacturing for advanced technology nodes. SRAF placement is required to adhere to manufacturability constraints (MRC). MRC specifications are distance and size constraints specified by the user to ensure SRAFs are not detrimental to the final target shapes being printed. Conceptually, SRAF placement can be divided into two steps - SRAF candidate generation and SRAF candidate cleanup or conflict resolution. SRAFs generated as candidates may not adhere to MRC constraints. It is during the cleanup/conflict resolution process that the MRC constraints are enforced. In this paper we focus on the latter phase - cleanup. The goal of the cleanup phase is to retain as much of the initial candidates as possible, and, if necessary, transform them to adhere to MRC conditions. An SRAF is said to be in conflict with another shape if it violates the distance MRC constraint. One can model these conflicts using a conflict graph G=(V,E), whose vertices V correspond to geometric shapes involved in a conflict and an edge is present in E, between two vertices if the corresponding shapes are involved in a conflict. A weight is associated with each vertex that could, for example, correspond to area of the corresponding shape. The goal of conflict resolution then, is to find a transformation of the vertices so that the resulting graph is conflict free while maximizing the weight of vertices retained. This can be viewed as a generalization of the computationally hard problem of finding the largest independent set of candidates, albeit allowing for transformation. The transformations we allow include deletion, splitting, resizing, merge, and bounded translation. In this paper, we describe an approach which classifies the conflicts and apply appropriate transformations to achieve effective SRAF placement. Further, we demonstrate that such a strategy reduces the number of rules to be specified by

  17. 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

  18. 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

  19. 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. PMID:26870757

  20. Biocompatibility test of polyhydroxybutyrate on human cell line.

    PubMed

    Raouf, A A; Samsudin, A R; Al-Joudi, F S; Shamsuria, O

    2004-05-01

    The human fibroblast MRC-5 cells incubated with PHB granules (TM) added at a final concentration of 4 mg/ml showed a time-course pattern of survival. The percentages of dead cells obtained were at the rate of 3.8% after 7 days, respectively. When the MRC-5 cells grown in different material, using the test concentration of 4 mg/ml PCM, they were found to show a similar time-course increasing pattern of death as that obtained with PHB. However, the death was noted in the cells incubated for 7 days, the death rates obtained was 40.54% respectively. PMID:15468838

  1. 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.

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

    PubMed

    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

  3. THE MMPI AS A MEASURE OF TREATMENT EFFECTS IN VOCATIONAL REHABILITATION. FINAL REPORT.

    ERIC Educational Resources Information Center

    COPELAND, WILLIAM C.; AND OTHERS

    THE MINNEAPOLIS REHABILITATION CENTER (MRC) STUDIED MINNESOTA MULTIPHASIC PERSONALITY INVENTORY (MMPI) SCORES TO SEE IF THEY RELIABLY PREDICTED EMPLOYMENT OUTCOME AND TREATMENT EFFECTS. IT WAS DEEMED IMPORTANT FOR AGENCIES TO HAVE A METHOD OF DIAGNOSING PROBABLE RETURN-TO-WORK CLIENTS BEFORE SELECTING THOSE FOR REHABILITATION. A METHOD OF…

  4. 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

  5. Improving the Representational Strategies of Children in a Music-Listening and Playing Task: An Intervention-Based Study

    ERIC Educational Resources Information Center

    Gil, Vicent; Reybrouck, Mark; Tejada, Jesús; Verschaffel, Lieven

    2015-01-01

    This intervention-based study focuses on the relation between music and its graphic representation from a meta-representational point of view. It aims to determine whether middle school students show an increase in meta-representational competence (MRC) after an educational intervention. Three classes of 11 to 14-year-old students participated in…

  6. 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...

  7. 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

  8. 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

  9. 78 FR 59994 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-30

    ... No. 34-70207 (August 15, 2013), 78 FR 51786 (August 21, 2013). II. Description OCC is amending its By-Laws and Rules to make structural changes to OCC's Membership/Risk Committee (``MRC'') regarding Public... Change to Revise OCC By-Laws and Rules to Make Structural Changes to OCC's Membership/Risk...

  10. 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…

  11. 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

  12. 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.

  13. 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.

  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. Analysis and Interpretation of Findings Using Multiple Regression Techniques

    ERIC Educational Resources Information Center

    Hoyt, William T.; Leierer, Stephen; Millington, Michael J.

    2006-01-01

    Multiple regression and correlation (MRC) methods form a flexible family of statistical techniques that can address a wide variety of different types of research questions of interest to rehabilitation professionals. In this article, we review basic concepts and terms, with an emphasis on interpretation of findings relevant to research questions…

  16. 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…

  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. PMID:26614440

  18. 78 FR 4184 - Self-Regulatory Organizations; NASDAQ OMX PHLX LLC; Notice of Filing and Immediate Effectiveness...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-01-18

    ... of Proposed Rule Change To Reduce the Fees Assessed for Certain Co-location Services January 14, 2013...) of the PHLX Fee Schedule for certain co-location services. PHLX is proposing that the implementation... of certain new co-location cabinets. The reduced MRC fees will apply to new cabinets ordered...

  19. 78 FR 51786 - Self-Regulatory Organizations; The Options Clearing Corporation; Notice of Filing of Proposed...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-21

    ... relevant part, Article III, Section 6A of OCC's By-Laws defines a Public Director as a person who is ``not... dealer in securities '' Currently, Article III, Section 9 of OCC's By-Laws specifies that at the first... flexibility to decide when it is best for new MRC member designations to be made. As amended, Article...

  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. Patterned ion exchange membranes for improved power production in microbial reverse-electrodialysis cells

    NASA Astrophysics Data System (ADS)

    Liu, Jia; Geise, Geoffrey M.; Luo, Xi; Hou, Huijie; Zhang, Fang; Feng, Yujie; Hickner, Michael A.; Logan, Bruce E.

    2014-12-01

    Power production in microbial reverse-electrodialysis cells (MRCs) can be limited by the internal resistance of the reverse electrodialysis stack. Typical MRC stacks use non-conductive spacers that block ion transport by the so-called spacer shadow effect. These spacers can be relatively thick compared to the membrane, and thus they increase internal stack resistance due to high solution (ohmic) resistance associated with a thick spacer. New types of patterned anion and cation exchange membranes were developed by casting membranes to create hemispherical protrusions on the membranes, enabling fluid flow between the membranes without the need for a non-conductive spacer. The use of the patterned membrane decreased the MRC stack resistance by ∼22 Ω, resulting in a 38% increase in power density from 2.50 ± 0.04 W m-2 (non-patterned membrane with a non-conductive spacer) to 3.44 ± 0.02 W m-2 (patterned membrane). The COD removal rate, coulombic efficiency, and energy efficiency of the MRC also increased using the patterned membranes compared to the non-patterned membranes. These results demonstrate that these patterned ion exchange membranes can be used to improve performance of an MRC.

  2. 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

  3. 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…

  4. 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

  5. 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.

  6. Psycholinguistic Word Information in Second Language Oral Discourse

    ERIC Educational Resources Information Center

    Salsbury, Tom; Crossley, Scott A.; McNamara, Danielle S.

    2011-01-01

    This study uses word information scores from the Medical Research Council (MRC) Psycholinguistic Database to analyse word development in the spontaneous speech data of six adult learners of English as a second language (L2) in a one-year longitudinal study. In contrast to broad measures of lexical development, such as word frequency and lexical…

  7. 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 ...

  8. Hysteresis and creep modeling and compensation for a piezoelectric actuator using a fractional-order Maxwell resistive capacitor approach

    NASA Astrophysics Data System (ADS)

    Liu, Yanfang; Shan, Jinjun; Gabbert, Ulrich; Qi, Naiming

    2013-11-01

    A physics-based fractional-order Maxwell resistive capacitor (FOMRC) model is proposed to characterize nonlinear hysteresis and creep behaviors of a piezoelectric actuator (PEA). The Maxwell resistive capacitor (MRC) model is interpreted physically in the electric domain for PEAs. Based on this interpretation, the MRC model is modified to directly describe the relationship between the input voltage and the output displacement of a PEA. Then a procedure is developed to identify the parameters of the MRC model. This procedure is capable of being carried out using the measured input and output of a PEA only. A fractional-order dynamics is integrated into the MRC model to describe the effect of creep, as well as the detachment of hysteresis loops caused by creep. Moreover, the inverse FOMRC model is constructed to compensate for hysteresis and creep in an open-loop positioning application of PEAs. Simulation and experiments are carried out to validate the proposed model. The PEA compensated by the inverse FOMRC model shows an excellent linear behavior.

  9. 32 CFR Appendix A to Part 47 - Instructions for Submitting Group Applications Under Public Law 95-202

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Under Public Law 95-202 A Appendix A to Part 47 National Defense Department of Defense OFFICE OF THE... Pt. 47, App. A Appendix A to Part 47—Instructions for Submitting Group Applications Under Public Law... Group Applications To: Secretary of the Air Force (SAF/MRC), DoD Civilian/Military Service Review...

  10. Regulation of Mitochondrial Respiratory Chain Biogenesis by Estrogens/Estrogen Receptors and Physiological, Pathological and Pharmacological Implications

    PubMed Central

    Chen, Jin-Qiang; Cammarata, Patrick R.; Baines, Christopher P.; Yager, James D.

    2009-01-01

    There has been increasing evidence pointing to the mitochondrial respiratory chain (MRC) as a novel and important target for the actions of 17β-estradiol(E2) and estrogen receptors (ER) in a number of cell types and tissues that have high demands for mitochondrial energy metabolism. This novel E2-mediated mitochondrial pathway involves the cooperation of both nuclear and mitochondrial ERα and ERβ and their co-activators on the coordinate regulation of both nuclear DNA- and mitochondrial DNA-encoded genes for MRC proteins. In this paper, we have: 1) comprehensively reviewed studies that reveal a novel role of estrogens and ERs in the regulation of MRC biogenesis; 2) discussed their physiological, pathological and pharmacological implications in the control of cell proliferation and apoptosis in relation to estrogen-mediated carcinogenesis, anticancer drug resistance in human breast cancer cells, neuro-protection for Alzheimer’s disease and Parkinson’s disease in brain, cardiovascular protection in human heart and their beneficial effects in lens physiology related to cataract in the eye; and 3) pointed out new research directions to address the key questions in this important and newly emerging area. We also suggest a novel conceptual approach that will contribute to innovative regimines for the prevention or treatment of a wide variety of medical complications based on E2/ER-mediated MRC biogenesis pathway. PMID:19559056

  11. 76 FR 56254 - Self-Regulatory Organizations; Municipal Securities Rulemaking Board; Notice of Filing of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-12

    ...-Payne Group''); the Education Finance Council (``EFC''); Fi360; Lewis Young Robertson & Burningham, Inc... LLC (``MRC''); the National Association of Independent Public Finance Advisors (``NAIPFA''); Not for... services (relating to corporate trust and mutual funds), such as shareholder servicing fees and 12b-1...

  12. Value of brain magnetic resonance imaging in mitochondrial respiratory chain disorders.

    PubMed

    Diogo, Luísa; Cordeiro, Miguel; Garcia, Paula; Fineza, Isabel; Moura, Cristina; Oliveira, Catarina Resende; Veiga, Margarida; Garcia, Teresa; Grazina, Manuela

    2010-03-01

    Mitochondrial respiratory chain (MRC) disorders have variable clinical manifestations which are mainly neurologic. Diagnosis in children is more complex than in adults because the classic phenotype, ragged red fibers, and mtDNA mutations are rarely seen in children. Moreover, clinical manifestations of disease in developing brains are less explicit. Although not specific, neuroimaging may be contributory to the diagnosis of these disorders in pediatric patients. Brain magnetic resonance images were reviewed for 133 pediatric patients investigated for a MRC disorder at a single center over a period of 10 years (1997-2006), in an attempt to identify distinctive neuroimaging features of MRC defects. Patients fit into four groups, according to the Bernier criteria: definite (63 cases), probable (53 cases), possible (7 cases) and unlikely diagnosis (10 cases). Brain atrophy (41 cases), supratentorial white matter lesions (14 cases), basal ganglia involvement (9 cases), and delayed myelination (9 cases) were the most frequent anomalies in the definite group, and 8 patients presented Leigh syndrome. Neuroimaging findings of the 63 children in the definite group were compared with the remainder and with those in the possible and unlikely groups. There were no significant differences in brain images between the groups analyzed, and therefore no distinctive brain imaging features were identified specific for MRC disorders. PMID:20159429

  13. 77 FR 31336 - Information Collection; Submission for OMB Review, Comment Request

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-05-25

    ... Evaluation of the Minnesota Reading Corps (MRC) for review and approval in accordance with the Paperwork... Minnesota Reading Corps on AmeriCorps member outcomes. Type of Review: New. Agency: Corporation for National and Community Service. Title: Process and Impact Evaluation of the Minnesota Reading Corps. OMB...

  14. 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. PMID:16832945

  15. 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...

  16. 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

  17. 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

  18. Clinical Outcomes following median to radial nerve transfers

    PubMed Central

    Ray, Wilson Z.; Mackinnon, Susan E.

    2010-01-01

    Purpose In this study the authors evaluate the clinical outcomes in patients with radial nerve palsy who underwent nerve transfers utilizing redundant fascicles of median nerve (innervating the flexor digitorum superficialis and flexor carpi radialis muscles) to the posterior interosseous nerve and the nerve to the extensor carpi radialis brevis. Methods A retrospective review of the clinical records of 19 patients with radial nerve injuries who underwent nerve transfer procedures using the median nerve as a donor nerve were included. All patients were evaluated using the Medical Research Council (MRC) grading system. Results The mean age of patients was 41 years (range 17 – 78 years). All patients received at least 12 months of follow-up (20.3 ± 5.8 months). Surgery was performed at a mean of 5.7 ± 1.9 months post-injury. Post-operative functional evaluation was graded according to the following scale: grades MRC 0/5 - MRC 2/5 were considered poor outcomes, while MRC of 3/5 was a fair result, MRC grade 4/5 was a good result, and grade 4+/5 was considered an excellent outcome. Seventeen patients (89%) had a complete radial nerve palsy while two patients (11%) had intact wrist extension but no finger or thumb extension. Post-operatively all patients except one had good to excellent recovery of wrist extension. Twelve patients recovered good to excellent finger and thumb extension, two patients had fair recovery, five patients had a poor recovery. Conclusions The radial nerve is a commonly injured nerve, causing significant morbidity in affected patients. The median nerve provides a reliable source of donor nerve fascicles for radial nerve reinnervation. This transfer was first performed in 1999 and evolved over the subsequent decade. The important nuances of both surgical technique and motor re-education critical for to the success of this transfer have been identified and are discussed. PMID:21168979

  19. Dengue Type 4 Live-Attenuated Vaccine Viruses Passaged in Vero Cells Affect Genetic Stability and Dengue-Induced Hemorrhaging in Mice

    PubMed Central

    Lee, Hsiang-Chi; Yen, Yu-Ting; Chen, Wen-Yu; Wu-Hsieh, Betty A.; Wu, Suh-Chin

    2011-01-01

    Most live-attenuated tetravalent dengue virus vaccines in current clinical trials are produced from Vero cells. In a previous study we demonstrated that an infectious cDNA clone-derived dengue type 4 (DEN-4) virus retains higher genetic stability in MRC-5 cells than in Vero cells. For this study we investigated two DEN-4 viruses: the infectious cDNA clone-derived DEN-4 2A and its derived 3′ NCR 30-nucleotide deletion mutant DEN-4 2AΔ30, a vaccine candidate. Mutations in the C-prM-E, NS2B-NS3, and NS4B-NS5 regions of the DEN genome were sequenced and compared following cell passages in Vero and MRC-5 cells. Our results indicate stronger genetic stability in both viruses following MRC-5 cell passages, leading to significantly lower RNA polymerase error rates when the DEN-4 virus is used for genome replication. Although no significant increases in virus titers were observed following cell passages, DEN-4 2A and DEN-4 2AΔ30 virus titers following Vero cell passages were 17-fold to 25-fold higher than titers following MRC-5 cell passages. Neurovirulence for DEN-4 2A and DEN-4 2AΔ30 viruses increased significantly following passages in Vero cells compared to passages in MRC-5 cells. In addition, more severe DEN-induced hemorrhaging in mice was noted following DEN-4 2A and DEN-4 2AΔ30 passages in Vero cells compared to passages in MRC-5 cells. Target mutagenesis performed on the DEN-4 2A infectious clone indicated that single point mutation of E-Q438H, E-V463L, NS2B-Q78H, and NS2B-A113T imperatively increased mouse hemorrhaging severity. The relationship between amino acid mutations acquired during Vero cell passage and enhanced DEN-induced hemorrhages in mice may be important for understanding DHF pathogenesis, as well as for the development of live-attenuated dengue vaccines. Taken together, the genetic stability, virus yield, and DEN-induced hemorrhaging all require further investigation in the context of live-attenuated DEN vaccine development. PMID:22053180

  20. Novel NSP1 genotype characterised in an African camel G8P[11] rotavirus strain.

    PubMed

    Jere, Khuzwayo C; Esona, Mathew D; Ali, Yahia H; Peenze, Ina; Roy, Sunando; Bowen, Michael D; Saeed, Intisar K; Khalafalla, Abdelmelik I; Nyaga, Martin M; Mphahlele, Jeffrey; Steele, Duncan; Seheri, Mapaseka L

    2014-01-01

    Animal-human interspecies transmission is thought to play a significant role in influencing rotavirus strain diversity in humans. Proving this concept requires a better understanding of the complete genetic constellation of rotaviruses circulating in various animal species. However, very few whole genomes of animal rotaviruses, especially in developing countries, are available. In this study, complete genetic configuration of the first African camel rotavirus strain (RVA/Camel-wt/SDN/MRC-DPRU447/2002/G8P[11]) was assigned a unique G8-P[11]-I2-R2-C2-M2-A18-N2-T6-E2-H3 genotype constellation that has not been reported in other ruminants. It contained a novel NSP1 genotype (genotype A18). The evolutionary dynamics of the genome segments of strain MRC-DPRU447 were rather complex compared to those found in other camelids. Its genome segments 1, 3, 7-10 were closely related (>93% nucleotide identity) to those of human-animal reassortant strains like RVA/Human-tc/ITA/PA169/1988/G6P[14] and RVA/Human-wt/HUN/Hun5/1997/G6P[14], segments 4, 6 and 11 shared common ancestry (>95% nucleotide identity) with bovine rotaviruses like strains RVA/Cow-wt/CHN/DQ-75/2008/G10P[11] and RVA/Cow-wt/KOR/KJ19-2/XXXX/G6P[7], whereas segment 2 was closely related (94% nucleotide identity) to guanaco rotavirus strain RVA/Guanaco-wt/ARG/Rio_Negro/1998/G8P[1]. Its genetic backbone consisted of DS-1-like, AU-1-like, artiodactyl-like and a novel A18 genotype. This suggests that strain MRC-DPRU447 potentially emerged through multiple reassortment events between several mammalian rotaviruses of at least two genogroups or simply strain MRC-DPRU447 display a unique progenitor genotypes. Close relationship between some of the genome segments of strain MRC-DPRU447 to human rotaviruses suggests previous occurrence of reassortment processes combined with interspecies transmission between humans and camels. The whole genome data for strain MRC-DPRU447 adds to the much needed animal rotavirus data from Africa

  1. 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

  2. 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

  3. The effect of the CYP1A2 *1F mutation on CYP1A2 inducibility in pregnant women

    PubMed Central

    Nordmark, Anna; Lundgren, Stefan; Ask, Birgitta; Granath, Fredrik; Rane, Anders

    2002-01-01

    Aims To investigate the influence of the CYP1A2*1F mutation on CYP1A2 activity in smoking and nonsmoking pregnant women. Methods Pregnant women (n = 904) who served as control subjects in a case-control study of early fetal loss were investigated. They were phenotyped for CYP1A2 using dietary caffeine and the urinary ratio AFMU + 1X + 1 U/1,7 U. An assay for CYP1A2*1F using 5′-nuclease assay (Taqman) was developed to genotype the population. Results The frequencies of *1 A and *1F alleles among Swedish women were 0.29 and 0.71, respectively. There was no statistically significant difference in CYP1A2 activity between the genotypes, although a trend towards enhanced activity was observed in *1F/*1F (log MRc 0.77) and *1F/*1 A (log MRc 0.82) genotypes compared with the *1 A/*1 A genotype (log MRc 0.71) (anovaP = 0.07). The mean difference between the *1 A homozygotes and the heterozygotes was 0.11 [95% confidence interval of the difference: (−0.21, −0.01)] and that between the *1 A and *1F homozygotes was 0.05 [95% confidence interval of the difference: (−0.13, 0.03)]. No significant effect (P = 0.22) of the *1F on CYP1A2 activity was observed in smokers, tested using an interaction term (smoking * genotype) in the anova model (*1F/*1F log MRc 0.79, *1F/*1 A log MRc 0.86, and *1 A/*1 A log MRc 0.73). In smokers, there was no difference in ratio between homozygotes for the *1 A and *1F alleles [mean difference −0.06; 95% confidence interval of the difference: −0.22, 0.11] or between *1 A/*1 A and *1 A/*1F genotypes [mean difference −0.13; 95% confidence interval of the difference: −0.29, 0.04]. Conclusions The effect of the CYP1A2*1F mutation on CYP1A2 activity in smoking pregnant women could not be confirmed. PMID:12445029

  4. 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

  5. A Multirobot Path-Planning Strategy for Autonomous Wilderness Search and Rescue.

    PubMed

    Macwan, Ashish; Vilela, Julio; Nejat, Goldie; Benhabib, Beno

    2015-09-01

    This paper presents a novel strategy for the on-line planning of optimal motion-paths for a team of autonomous ground robots engaged in wilderness search and rescue (WiSAR). The proposed strategy, which forms part of an overall multirobot coordination (MRC) methodology, addresses the dynamic nature of WiSAR by: 1) planning initial, time-optimal, and piecewise polynomial paths for all robots; 2) implementing and regularly evaluating the optimality of the paths through a set of checks that gauge feasibility of path-completion within the available time; and 3) replanning paths, on-line, whenever deemed necessary. The fundamental principle of maintaining the optimal deployment of the robots throughout the search guides the MRC methodology. The proposed path-planning strategy is illustrated through a simulated realistic WiSAR example, and compared to an alternative, nonprobabilistic approach. PMID:25376050

  6. A stromal cell niche for human and mouse type 3 innate lymphoid cells ¶

    PubMed Central

    Li, Zhi; Thuery, Anne; Papazian, Natalie; Withers, David R.; Coles, Mark C.; Cupedo, Tom

    2015-01-01

    Adaptive immunity critically depends on the functional compartmentalization of secondary lymphoid organs. Mesenchymal stromal cells create and maintain specialized niches that support survival, activation and expansion of T and B cells, and integrated analysis of lymphocytes and their niche has been instrumental in understanding adaptive immunity. Lymphoid organs are also home to type 3 innate lymphoid cells (ILC3), innate effector cells essential for barrier immunity. However, a specialized stromal niche for ILC3 has not been identified. A novel lineage-tracing approach now identifies a subset of murine fetal lymphoid tissue organizer cells that gives rise exclusively to adult marginal reticular cells (MRC). Moreover, both cell types are conserved from mouse to human and co-localize with ILC3 in secondary lymphoid tissues throughout life. In sum, we provide evidence that fetal stromal organizers give rise to adult MRC and form a dedicated stromal niche for innate ILC3 in adaptive lymphoid organs. PMID:26378073

  7. Transplants in Adult ALL--? Allo for everyone.

    PubMed

    Goldstone, Anthony H

    2009-01-01

    The large MRC/ECOG adult acute lymphoblastic leukemia (ALL) study establishes the value of sibling donor allogeneic transplant in standard-risk patients demonstrating superior outcome to conventional chemotherapy. The small but significant number of patients having matched unrelated donor (MUD) transplants on this study protocol appear to do well, and may establish the value of such an approach for those without a sibling. Reduced-intensity conditioning (RIC) conditioning might begin to address the transplant-related mortality problems of the older patients. The youngest adults may not need a transplant at all. If they are now treated on pediatric chemotherapy protocols, their outcome appears to improve significantly. The MRC/ECOG study, the emerging MUD and RIC data all help establish allogeneic transplant more widely in this disease. PMID:19147069

  8. 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

  9. Drug-Induced Mitochondrial Toxicity.

    PubMed

    Hargreaves, Iain P; Al Shahrani, Mesfer; Wainwright, Luke; Heales, Simon J R

    2016-07-01

    The mitochondrial respiratory chain (MRC) and ATP synthase (complex V) play an essential role in cellular energy production by the process of oxidative phosphorylation. In addition to inborn errors of metabolism, as well as secondary causes from disease pathophysiology, an impairment of oxidative phosphorylation can result from drug toxicity. These 'off-target' pharmacological effects can occur from a direct inhibition of MRC enzyme activity, an induction of mitochondrial oxidative stress, an uncoupling of oxidative phosphorylation, an impairment of mitochondrial membrane structure or a disruption in the replication of mitochondrial DNA. The purpose of this review is to focus on the off-target mitochondrial toxicity associated with both commonly used pharmacotherapies and a topical 'weight loss' agent. The mechanisms of drug-induced mitochondrial impairment will be discussed together with putative therapeutic strategies to counteract the adverse effects of the pharmacotherapy. PMID:26992920

  10. Microbial reservoir characterization: An integration of surface geochemistry and developmental geology data

    SciTech Connect

    Hitzman, D.; Tucker, J.; Rountree, B. )

    1996-01-01

    Microbial Reservoir Characterization (MRC) integrates measurements of hydrocarbon microseepage escaping from petroleum reservoirs with developmental geologic and engineering data for an enhanced identification of the subsurface reservoir fabric. Studies from mature producing fields demonstrate MRC technology can monitor subsurface fluid withdrawal patterns with microseepage patterns identified from surface soil samples. Areas of the reservoir in contact with producing wells, by-passed production, and reservoir heterogeneity characteristics can be identified. Microbial ER microseepage links the distribution of hydrocarbon traps with the continuity (compartments) of a reservoir, as well as locates areas prone to higher quality reserves. Upward, buoyancy driven forces controlling hydrocarbon microseepage is altered along pressure pathways streaming to production wells. In these cases, microseepage is essentially shut down and lower concentrations of gases reach the surface environment. Case studies from a variety of basin environments will be presented.

  11. Microbial reservoir characterization: An integration of surface geochemistry and developmental geology data

    SciTech Connect

    Hitzman, D.; Tucker, J.; Rountree, B.

    1996-12-31

    Microbial Reservoir Characterization (MRC) integrates measurements of hydrocarbon microseepage escaping from petroleum reservoirs with developmental geologic and engineering data for an enhanced identification of the subsurface reservoir fabric. Studies from mature producing fields demonstrate MRC technology can monitor subsurface fluid withdrawal patterns with microseepage patterns identified from surface soil samples. Areas of the reservoir in contact with producing wells, by-passed production, and reservoir heterogeneity characteristics can be identified. Microbial ER microseepage links the distribution of hydrocarbon traps with the continuity (compartments) of a reservoir, as well as locates areas prone to higher quality reserves. Upward, buoyancy driven forces controlling hydrocarbon microseepage is altered along pressure pathways streaming to production wells. In these cases, microseepage is essentially shut down and lower concentrations of gases reach the surface environment. Case studies from a variety of basin environments will be presented.

  12. 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.

  13. 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

  14. 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.

  15. 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. PMID:26187285

  16. Performance Analysis of the Blind Minimum Output Variance Estimator for Carrier Frequency Offset in OFDM Systems

    NASA Astrophysics Data System (ADS)

    Yang, Feng; Li, Kwok H.; Teh, Kah C.

    2006-12-01

    Carrier frequency offset (CFO) is a serious drawback in orthogonal frequency division multiplexing (OFDM) systems. It must be estimated and compensated before demodulation to guarantee the system performance. In this paper, we examine the performance of a blind minimum output variance (MOV) estimator. Based on the derived probability density function (PDF) of the output magnitude, its mean and variance are obtained and it is observed that the variance reaches the minimum when there is no frequency offset. This observation motivates the development of the proposed MOV estimator. The theoretical mean-square error (MSE) of the MOV estimator over an AWGN channel is obtained. The analytical results are in good agreement with the simulation results. The performance evaluation of the MOV estimator is extended to a frequency-selective fading channel and the maximal-ratio combining (MRC) technique is applied to enhance the MOV estimator's performance. Simulation results show that the MRC technique significantly improves the accuracy of the MOV estimator.

  17. The final two redshifts for radio sources from the equatorial BRL sample

    NASA Astrophysics Data System (ADS)

    Best, P. N.; Peacock, J. A.; Brookes, M. H.; Dowsett, R. E.; Röttgering, H. J. A.; Dunlop, J. S.; Lehnert, M. D.

    2003-12-01

    Best, Röttgering & Lehnert (BRL) defined a new sample of powerful radio sources from the Molonglo Reference Catalogue, for which redshifts were compiled or measured for 177 of the 178 objects. For the final object, MRC1059-010 (3C 249), the host galaxy is identified here using near-infrared imaging, and the redshift is determined from Very Large Telescope (VLT) spectroscopy. For one other object in the sample, MRC0320+053 (4C05.14), the literature redshift has been questioned: new spectroscopic observations of this object are presented, deriving a corrected redshift. With these two results, the spectroscopic completeness of this sample is now 100 per cent. New redshifts are also presented for PKS0742+10 from the Wall & Peacock 2.7-GHz catalogue, and for PKS1336+003 from the Parkes Selected Regions. PKS0742+10 shows a strong neutral hydrogen absorption feature in its Lyman α emission profile.

  18. In vitro evaluation of cytotoxic and mutagenic activity of avarol.

    PubMed

    Pejin, Boris; Iodice, Carmine; Kojic, Vesna; Jakimov, Dimitar; Lazovic, Milica; Tommonaro, Giuseppina

    2016-06-01

    The cytotoxicity of avarol, a main secondary metabolite of the Mediterranean sponge Dysidea avara, was in vitro screened by MTT assay against four human tumour cell lines. The colon HT-29 tumour cells practically showed to be the only sensitive ones towards this organic compound. No toxicity was found against the fetal lung fibroblast MRC-5 cells at the concentrations tested. In comparison with doxorubicin, used as a positive control, avarol actually exhibited at least 588-fold less toxicity towards normal MRC-5 cells. Finally, comet assay indicated that DNA fragmentation was almost fivefold higher upon the treatment with doxorubicin, compared to avarol. The obtained results have actually confirmed that avarol scaffold may contribute to development of new cytostatics inspired by nature. PMID:26181496

  19. 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.

  20. Optical diversity transmission using WDM signal and phase-conjugate lights through multi-core fiber.

    PubMed

    Koga, Masafumi; Moroi, Mitsuki; Takara, Hidehiko

    2016-05-01

    This paper proposes a maximum-ratio combining (MRC) scheme for a WDM signal and phase-conjugate pair (PCP) diversity transmission to cancel nonlinear phase-shift. A transfer function approximation for nonlinear phase-shift cancellation is formulated. It shows, with the help of a numerical calculation, that span-by-span chromatic dispersion compensation is more effective than the lumped equivalent at the receiver. This is confirmed in a 2-core diversity 5 channel WDM transmission experiment over 3-spans of 60km MCF with 25 Gbit/s-QPSK PCP. The peak Q-value was enhanced by 3.6dB through MRC, resulting in superior bitrate-distance product and optical power density limit, compared to twice the single core transmission. PMID:27137550

  1. GSATools: analysis of allosteric communication and functional local motions using a structural alphabet

    PubMed Central

    Pandini, Alessandro; Fornili, Arianna; Fraternali, Franca; Kleinjung, Jens

    2013-01-01

    Motivation: GSATools is a free software package to analyze conformational ensembles and to detect functional motions in proteins by means of a structural alphabet. The software integrates with the widely used GROMACS simulation package and can generate a range of graphical outputs. Three applications can be supported: (i) investigation of the conformational variability of local structures; (ii) detection of allosteric communication; and (iii) identification of local regions that are critical for global functional motions. These analyses provide insights into the dynamics of proteins and allow for targeted design of functional mutants in theoretical and experimental studies. Availability: The C source code of the GSATools, along with a set of pre-compiled binaries, is freely available under GNU General Public License from http://mathbio.nimr.mrc.ac.uk/wiki/GSATools. Contact: alessandro.pandini@kcl.ac.uk or jkleinj@nimr.mrc.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:23740748

  2. 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

  3. Validation of Rules to Predict Emergent Surgical Intervention in Pediatric Trauma Patients

    PubMed Central

    Boatright, Dowin H; Byyny, Richard L; Hopkins, Emily; Bakes, Katherine; Hissett, Jennifer; Tunson, Java; Easter, Joshua S; Vogel, Jody A; Bensard, Denis; Haukoos, Jason S

    2014-01-01

    Background Trauma centers use guidelines to determine when a trauma surgeon is needed in the emergency department (ED) on patient arrival. A decision rule from Loma Linda University identified patients with penetrating injury and tachycardia as requiring emergent surgical intervention. Our goal was to validate this rule and to compare it to the American College of Surgeons’ Major Resuscitation Criteria (MRC). Study Design We used data from 1993 through 2010 from two Level 1 trauma centers in Denver, Colorado. Patient demographics, injury severity, times of ED arrival and surgical intervention, and all variables of the Loma Linda Rule and the MRC were obtained. The outcome, emergent intervention (defined as requiring operative intervention by a trauma surgeon within one hour of arrival to the ED or performance of cricothyroidotomy or thoracotomy in the ED) was confirmed using standardized abstraction. Sensitivities, specificities, and 95% confidence intervals (CIs) were calculated. Results 8,078 patients were included and 47 (0.6%) required emergent intervention. Of the 47 patients, the median age was 11 years (IQR: 7–14), 70% were male, 30% had penetrating mechanisms, and the median ISS was 25 (IQR: 9–41). At the two institutions, the Loma Linda Rule had a sensitivity and specificity of 69% (95% CI: 45%–94%) and 76% (95% CI: 69%–83%), respectively, and the MRC had a sensitivity and specificity of 80% (95% CI: 70%–92%) and 81% (95% CI: 77%–85%), respectively. Conclusions Emergent surgical intervention is rare in the pediatric trauma population. Although precision of predictive accuracies of the Loma Linda Rule and MRC were limited by small numbers of outcomes, neither set of criteria appears to be sufficiently accurate to recommend their routine use. PMID:23623222

  4. 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

  5. Physical Activity Characteristics across GOLD Quadrants Depend on the Questionnaire Used

    PubMed Central

    Demeyer, Heleen; Gimeno-Santos, Elena; Rabinovich, Roberto A.; Hornikx, Miek; Louvaris, Zafeiris; de Boer, Willem I.; Karlsson, Niklas; de Jong, Corina; Van der Molen, Thys; Vogiatzis, Ioannis; Janssens, Wim; Garcia-Aymerich, Judith; Troosters, Thierry; Polkey, Michael I.

    2016-01-01

    Background The GOLD multidimensional classification of COPD severity combines the exacerbation risk with the symptom experience, for which 3 different questionnaires are permitted. This study investigated differences in physical activity (PA) in the different GOLD quadrants and patient’s distribution in relation to the questionnaire used. Methods 136 COPD patients (58±21% FEV1 predicted, 34F/102M) completed COPD assessment test (CAT), clinical COPD questionnaire (CCQ) and modified Medical Research Council (mMRC) questionnaire. Exacerbation history, spirometry and 6MWD were collected. PA was objectively measured for 2 periods of 1 week, 6 months apart, in 5 European centres; to minimise seasonal and clinical variation the average of these two periods was used for analysis. Results GOLD quadrants C+D had reduced PA compared with A+B (3824 [2976] vs. 5508 [4671] steps.d-1, p<0.0001). The choice of questionnaire yielded different patient distributions (agreement mMRC-CAT κ = 0.57; CCQ-mMRC κ = 0.71; CCQ-CAT κ = 0.72) with different clinical characteristics. PA was notably lower in patients with an mMRC score ≥2 (3430 [2537] vs. 5443 [3776] steps.d-1, p <0.001) in both the low and high risk quadrants. Conclusions Using different questionnaires changes the patient distribution and results in different clinical characteristics. Therefore, standardization of the questionnaire used for classification is critical to allow comparison of different studies using this as an entry criterion. Clinical Trial Registration ClinicalTrials.gov NCT01388218 PMID:26974332

  6. Hysteresis compensation and trajectory preshaping for piezoactuators in scanning applications

    NASA Astrophysics Data System (ADS)

    Liu, Yanfang; Shan, Jinjun; Gabbert, Ulrich; Qi, Naiming

    2014-01-01

    This paper focuses on the dynamics and control of piezoactuators (PEAs) for high-speed large-range scanning applications. Firstly, the nonlinear hysteresis is modeled by using a modified Maxwell resistive capacitor (MRC) model. Secondly, an inverse-based feedforward controller is proposed for this application with hysteresis compensation. Then, the scanning trajectories are preshaped by treating the hysteresis-compensated PEA as a linear system. Finally, experiments are conducted to verify the effectiveness of the proposed approaches.

  7. 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.

  8. 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

  9. Extreme genetic diversity of methicillin-resistant Staphylococcus epidermidis strains disseminated among healthy Japanese children.

    PubMed

    Jamaluddin, Tengku Zetty Maztura Tengku; Kuwahara-Arai, Kyoko; Hisata, Ken; Terasawa, Masahiko; Cui, Longzhu; Baba, Tadashi; Sotozono, Chie; Kinoshita, Shigeru; Ito, Teruyo; Hiramatsu, Keiichi

    2008-11-01

    For the past few years, we have been observing the dissemination of methicillin-resistant staphylococci in the community. From 2001 to 2003, an evaluation of nasal samples from 1,285 children in five day-care centers and two kindergartens in three districts in Japan revealed that methicillin-resistant coagulase-negative staphylococci (MRC-NS) have been widely disseminated in the Japanese community. Their prevalence is much greater than community-acquired methicillin-resistant Staphylococcus aureus (CA-MRSA). Forty-nine children (3.81%) were colonized with MRSA, whereas 390 children (30.35%) were colonized with MRC-NS. These MRC-NS strains predominantly harbored a pair of cassette chromosome recombinase types A2 and B2 (ccrAB2). Of these, 40.8% harbored type IVa staphylococcal cassette chromosome mec (SCCmec) elements, a distinct/characteristic type of SCCmec in pandemic clones of CA-MRSA. Interestingly, there was also a high frequency of nontypeable strains which possessed atypical structures compared to previous SCCmec types. Among the MRC-NS, the majority of strains (63.59%) were methicillin-resistant Staphylococcus epidermidis (MRSE). Their genotypes, as judged from pulsed-field gel electrophoresis (PFGE), were highly diverse. They were so diverse that there was no sign of an immediate transmission of any MRSE clone among children in the same institutions. In a previous report, we expounded that a few CA-MRSA clones with distinct SCCmec types were disseminated among children in the same institutions. Au contraire, with the case of CA-MRSE, there was no single genotype of CA-MRSE disseminated among children even in the same institution or class. PMID:18832123

  10. 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

  11. Fully automated objective-based method for master recession curve separation.

    PubMed

    Posavec, Kristijan; Parlov, Jelena; Nakić, Zoran

    2010-01-01

    The fully automated objective-based method for master recession curve (MRC) separation was developed by using Microsoft Excel spreadsheet and Visual Basic for Applications (VBA) code. The core of the program code is used to construct an MRC by using the adapted matching strip method (Posavec et al. 2006). Criteria for separating the MRC into two or three segments are determined from the flow-duration curve and are represented as the probable range of percent of flow rate duration. Successive separations are performed automatically on two and three MRCs using sets of percent of flow rate duration from selected ranges and an optimal separation model scenario, having the highest average coefficient of determination R(2), is selected as the most appropriate one. The resulting separated master recession curves are presented graphically, whereas the statistics are presented numerically, all in separate sheets. Examples of field data obtained from two springs in Istria, Croatia, are used to illustrate its application. The freely available Excel spreadsheet and VBA program ensures the ease of use and applicability for larger data sets. PMID:20100291

  12. 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

  13. 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

  14. 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.

  15. 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

  16. The Hydractinia echinata test-system. III: Structure-toxicity relationship study of some azo-, azo-anilide, and diazonium salt derivatives.

    PubMed

    Chicu, Sergiu Adrian; Munteanu, Melania; Cîtu, Ioana; Soica, Codruta; Dehelean, Cristina; Trandafirescu, Cristina; Funar-Timofei, Simona; Ionescu, Daniela; Simu, Georgeta Maria

    2014-01-01

    Structure-toxicity relationships for a series of 75 azo and azo-anilide dyes and five diazonium salts were developed using Hydractinia echinata (H. echinata) as model species. In addition, based on these relationships, predictions for 58 other azo-dyes were made. The experimental results showed that the measured effectiveness Mlog(1/MRC50) does not depend on the number of azo groups or the ones corresponding to metobolites, but it is influenced by the number of anilide groups, as well as by the substituents' positions within molecules. The conformational analysis pointed out the intramolecular hydrogen bonds, especially the simple tautomerization of quinoidic (STOH) or aminoidic (STNH2) type. The effectiveness is strongly influenced by the "push-pull" electronic effect, specific to two hydroxy or amino groups separated by an azo moiety (double alternate tautomery, (DAT), to the -COOH or -SO3H groups which are located in ortho or para position with respect to the azo group. The levels of the lipophylic/hydrophilic, electronic and steric equilibriums, pointed out by the Mlog(1/MRC50) values, enabled the calculation of their average values Clog(1/MRC50) ("Köln model"), characteristic to one derivative class (class isotoxicity). The azo group reduction and the hydrolysis of the amido/peptidic group are two concurrent enzymatic reactions, which occur with different reaction rates and mechanisms. The products of the partial biodegradation are aromatic amines. No additive or synergic effects are noticed among them. PMID:25006787

  17. 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.

  18. Syndromes associated with mitochondrial DNA depletion

    PubMed Central

    2014-01-01

    Mitochondrial dysfunction accounts for a large group of inherited metabolic disorders most of which are due to a dysfunctional mitochondrial respiratory chain (MRC) and, consequently, deficient energy production. MRC function depends on the coordinated expression of both nuclear (nDNA) and mitochondrial (mtDNA) genomes. Thus, mitochondrial diseases can be caused by genetic defects in either the mitochondrial or the nuclear genome, or in the cross-talk between the two. This impaired cross-talk gives rise to so-called nuclear-mitochondrial intergenomic communication disorders, which result in loss or instability of the mitochondrial genome and, in turn, impaired maintenance of qualitative and quantitative mtDNA integrity. In children, most MRC disorders are associated with nuclear gene defects rather than alterations in the mtDNA itself. The mitochondrial DNA depletion syndromes (MDSs) are a clinically heterogeneous group of disorders with an autosomal recessive pattern of transmission that have onset in infancy or early childhood and are characterized by a reduced number of copies of mtDNA in affected tissues and organs. The MDSs can be divided into least four clinical presentations: hepatocerebral, myopathic, encephalomyopathic and neurogastrointestinal. The focus of this review is to offer an overview of these syndromes, listing the clinical phenotypes, together with their relative frequency, mutational spectrum, and possible insights for improving diagnostic strategies. PMID:24708634

  19. Mutations in COX7B Cause Microphthalmia with Linear Skin Lesions, an Unconventional Mitochondrial Disease

    PubMed Central

    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

    2012-01-01

    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. PMID:23122588

  20. Magnetic Resonance Imaging Measurements of Film Cooling Effectiveness

    NASA Astrophysics Data System (ADS)

    Elkins, Christopher; Alley, Marcus; Eaton, John

    2009-11-01

    Film cooling through holes and slots is used extensively in gas turbine engines to protect combustor walls, stator vanes, and turbine blades. Film cooling effectiveness has been shown to depend on myriad geometrical and flow parameters. Magnetic Resonance Velocimetry (MRV) and Concentration (MRC) measurements efficiently acquire entire 3D velocity and scalar information making them well suited to investigate the large design parameter space. In addition, MRV and MRC provide information in the film supply plenum and hole which is traditionally unobtainable. Here, MRC is extended to near wall measurements to determine film cooling effectiveness. Measurements are made for a single film hole (d=5.8 mm, l/d=4 and α=30 ) in the wall of a square channel. Velocity and scalar concentration data are presented for multiple blowing ratios. The data show the evolution of vortices around the jets, the coolant mixing, and the 2D film cooling effectiveness distribution. Measurements within the plenum and injection hole show the origin of specific flow structures.

  1. Confocal scanning laser microscopy with complementary 3D image analysis allows quantitative studies of functional state of ionoregulatory cells in the Nile tilapia (Oreochromis niloticus) following salinity challenge.

    PubMed

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

    2013-04-01

    The development of a novel three-dimensional image analysis technique of stacks generated by confocal laser scanning microscopy is described allowing visualization of mitochondria-rich cells (MRCs) in the seawater-adapted Nile tilapia in relation to their spatial location. This method permits the assessment and classification of both active and nonactive MRCs based on the distance of the top of the immunopositive cell from the epithelial surface. In addition, this technique offers the potential for informative and quantitative studies, for example, densitometric and morphometric measurements based on MRC functional state. Confocal scanning laser microscopy used with triple staining whole-mount immunohistochemistry was used to detect integumental MRCs in the yolk-sac larvae tail of the Nile tilapia following transfer from freshwater to elevated salinities, that is, 12.5 and 20 ppt. Mean active MRC volume was always significantly larger and displayed a greater staining intensity (GLM; P<0.05) than nonactive MRCs. Following transfer, the percentage of active MRCs was seen to increase as did MRC volume (GLM; P<0.05). PMID:23390074

  2. 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

  3. The Nude Mutant Gene Foxn1 is a HOXC13 Regulatory Target during Hair Follicle and Nail Differentiation

    PubMed Central

    Potter, Christopher S.; Pruett, Nathanael D.; Kern, Michael J.; Baybo, Mary Ann; Godwin, Alan R.; Potter, Kathleen A.; Peterson, Ron L.; Sundberg, John P.; Awgulewitsch, Alexander

    2011-01-01

    Among the Hox genes, Hoxc13 has been shown to be essential for proper hair shaft differentiation as Hoxc13 gene-targeted (Hoxc13tm1Mrc) mice completely lack external hair. Because of the remarkable overt phenotypic parallels to the Foxn1nu (nude) mutant mice, we sought to determine whether Hoxc13 and Foxn1 might act in a common pathway of hair follicle (HF) differentiation. We show that the alopecia exhibited by both the Hoxc13tm1Mrc and Foxn1nu mice is due to strikingly similar defects in hair shaft differentiation and that both mutants suffer from a severe nail dystrophy. These phenotypic similarities are consistent with the extensive overlap between Hoxc13 and Foxn1 expression patterns in the HF and the nail matrix. Furthermore, DNA microarray analysis of skin from Hoxc13tm1Mrc mice identified Foxn1 as significantly down-regulated along with numerous hair keratin genes. This Foxn1 down-regulation apparently reflects the loss of direct transcriptional control by HOXC13 as indicated by our results obtained through co-transfection and chromatin immunoprecipitation (ChIP) assays. As presented in the discussion, these data support a regulatory model of keratinocyte differentiation in which HOXC13-dependent activation of Foxn1 is part of a regulatory cascade controlling the expression of terminal differentiation markers. PMID:21191399

  4. 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. PMID:24892227

  5. 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

  6. Eutectic experiment development for space processing

    NASA Technical Reports Server (NTRS)

    Hopkins, R. H.

    1972-01-01

    A ground base test plan and a specimen evaluation scheme have been developed for the aluminum-copper eutectic solidification experiment to be run in the M518 multipurpose electric furnace during the Skylab mission. Besides thermal and solidification studies a detailed description is given of the quantitative metallographic technique which is appropriate for characterizing eutectic structures. This method should prove a key tool for evaluating specimen microstructure which is the most sensitive indicator of changes produced during solidification. It has been recommended that single grain pre-frozen eutectic specimens be used to simplify microstructural evaluation and to eliminate any porosity in the as-cast eutectic specimens. High purity (99.999%) materials from one supplier should be employed for all experiments. Laboratory studies indicate that porosity occurs in the MRC as-cast eutectic ingots but that this porosity can be eliminated by directional freezing. Chemical analysis shows that the MRC ingots are slightly Al rich and contain about .03% impurity. Because of the impurity content the lower cooldown rate (1.2 C/min) should be used for eutectic freezing if MRC material is used in the M518 furnace.

  7. 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

  8. 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

  9. Maximum reservoir capacity of vegetation for persistent organic pollutants: Implications for global cycling

    NASA Astrophysics Data System (ADS)

    Dalla Valle, Matteo; Dachs, Jordi; Sweetman, Andrew J.; Jones, Kevin C.

    2004-12-01

    The concept of maximum reservoir capacity (MRC) or "equilibrium capacity ratio," the ratio of the capacities of the vegetation and of the atmospheric mixed layer (AML) to hold chemical under equilibrium conditions, is applied to selected persistent organic pollutants (POPs) in vegetation in order to assess its importance for the global cycling of POPs. Vegetation is found to have a significant storage capacity, and because of its intimate contact with the atmosphere may play an important role in global cycling of POPs. The vegetation MRC is calculated for some representative PCB congeners (PCB-28; -152; -180) at the global scale with a spatial resolution of 0.25° × 0.25°. It is shown to be comparable to that of the skin layer of the soil and to vary over many orders of magnitude, between compounds, locations, and time (seasonally/diurnally), depending on the vegetation type and on the temperature. The highest MRC values are observed in areas with low temperatures and coniferous forests (e.g., Siberia, Canada, Scandinavia), while the lowest values are typically located in warm and desert areas (e.g., Sahara). Large differences were also observed at the regional scale. Implications for the global cycling and long-range atmospheric transport (LRAT) of POPs are discussed, including comparisons with soil and ocean MRCs, which will drive net transfers of POPs between media and regions.

  10. 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

  11. A novel mutation in FBXL4 in a Norwegian child with encephalomyopathic mitochondrial DNA depletion syndrome 13.

    PubMed

    Barøy, Tuva; Pedurupillay, Christeen Ramane J; Bliksrud, Yngve T; Rasmussen, Magnhild; Holmgren, Asbjørn; Vigeland, Magnus D; Hughes, Timothy; Brink, Maaike; Rodenburg, Richard; Nedregaard, Bård; Strømme, Petter; Frengen, Eirik; Misceo, Doriana

    2016-06-01

    Mitochondrial DNA depletion syndromes (MTDPS) represent a clinically and genetically heterogeneous group of autosomal recessive disorders, caused by mutations in genes involved in maintenance of mitochondrial DNA (mtDNA). Biallelic mutations in FBXL4 were recently described to cause encephalomyopathic MTDPS13. The syndrome has infantile onset and presents with hypotonia, feeding difficulties, a pattern of mild facial dysmorphisms, global developmental delay and brain atrophy. Laboratory investigations reveal elevated blood lactate levels, unspecific mitochondrial respiratory chain (MRC) enzyme deficiencies and mtDNA depletion. We report a novel missense variant, c.1442T > C (p.Leu481Pro), in FBXL4 (NM_012160.4) in a Norwegian boy with clinical, biochemical and cerebral MRI characteristics consistent with MTDPS13. The FBXL4 c.1442T > C (p.Leu481Pro) variant was not present in public databases, 149 Norwegian controls nor an in-house database containing whole exome sequencing data from 440 individuals, and it was predicted in silico to be deleterious to the protein function. Activities of MRC enzymes were normal in muscle tissue (complexes I-IV) and cultured skin fibroblasts (complexes I-V) from the patient, but mtDNA depletion was confirmed in muscle, thus supporting the predicted pathogenicity of the FBXL4 c.1442T > C (p.Leu481Pro) variant. On clinical indication of mitochondrial encephalomyopathy, sequencing of FBXL4 should be performed, even when the activity levels of the MRC enzymes are normal. PMID:27182039

  12. 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

  13. 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

  14. 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

  15. Validation of the Clinical COPD Questionnaire in Taiwan.

    PubMed

    Lin, Wei-Chun; Huang, Tsuey-Yuan; Liu, Chieh-Yu; Yeh, Mei-Ling; Yu, Chia-Hui; Hwang, Shiow-Li

    2016-06-01

    Health status improvement is a critical treatment goal for physicians managing chronic obstructive pulmonary disease (COPD). Numerous instruments to measure the disease-specific health-related quality of life (HRQOL) for patients with COPD have been used in daily clinical practice. The Clinical COPD Questionnaire (CCQ) is one of these recommended by the Global Initiative for Chronic Obstructive Lung Disease (GOLD). This study examined the psychometric properties of the CCQ in patients with COPD in Taiwan. A descriptive, cross-sectional design was conducted. Data were collected in a secondary care unit. We administered the CCQ, the modified Medical Research Council (mMRC) dyspnea scale, and the 12-item Short Form Health Survey (SF-12) for patients with COPD. Reliability was assessed using Cronbach's alpha and item-total correlation coefficients. Construct validity was assessed using confirmatory factor analysis (CFA) and testing the hypothesis that severity of dyspnea measured using the mMRC dyspnea scale is associated with the CCQ scores. Convergent validity was assessed by testing the correlation between the CCQ and the SF-12. Discriminant validity was assessed to differentiate among the classifications of COPD Groups A to D. A total of 114 subjects were recruited in the study. Cronbach's alpha was high (0.90) for the total score of the CCQ. Significant correlations were found between the CCQ scores and those of the mMRC dyspnea scale (ρ = 0.67) and domains of the SF-12 (ρ = -0.44 to -0.75). Furthermore, the CCQ scores showed a significant difference among the classifications of COPD Groups A to D. CFA confirmed the construct validity, with a good model fit. Good to excellent psychometric properties of the Chinese Version CCQ were demonstrated in the study. Wide usage of the Chinese Version CCQ for Taiwanese COPD patients can be recommended in daily clinical practice or clinical trials. PMID:26678264

  16. Clinical characteristics of idiopathic pulmonary fibrosis patients according to their smoking status

    PubMed Central

    Nagano, Hiroaki; Nei, Yuichiro; Yamashiro, Shin

    2016-01-01

    Background Idiopathic pulmonary fibrosis (IPF) is the most common form of idiopathic interstitial pneumonias (IIPs) of unknown etiology that often affects male, elderly smokers. However, it is sometimes observed in never smokers. This study aimed to clarify the clinical characteristics of IPF in never-smoking patients compared with those in smoking patients. Methods We retrospectively reviewed medical records, pulmonary function tests, and chest high-resolution computed tomography (HRCT) scan of never-smoking and smoking IPF patients from July 1, 2008 to June 30, 2013 at our hospital. Results We identified 32 never-smoking IPF patients and 66 smoking IPF patients. Never-smoking IPF patients developed more acute exacerbation (AE) than smoking IPF patients (50% vs. 18.2%, P<0.0001). The strongest predictor of AE in never-smoking IPF was modified Medical Research Council (mMRC) breathlessness scale [Hazards ratio (HR), 2.84, P=0.006]. The median survival time of never-smoking and smoking were 18.5 (0.1–138) and 26.3 (0.1–98.4) months, P<0.0001, respectively. The Cox proportional hazard model showed that 1-year mMRC breathlessness scale (HR, 3.24, P=0.001) and gender, age, and physiology (GAP) score (HR, 1.59, P=0.029) were strong predictors of mortality in never-smoking IPF patients at our hospital. Conclusions In conclusion, never-smoking IPF patients developed AE more often and showed poor prognosis compared with smoking IPF patients. The 1-year mMRC breathlessness scale was an important predictor of mortality at our hospital. PMID:27293827

  17. 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.

  18. Angiopoietin-2 regulates gene expression in TIE2-expressing monocytes and augments their inherent proangiogenic functions.

    PubMed

    Coffelt, Seth B; Tal, Andrea O; Scholz, Alexander; De Palma, Michele; Patel, Sunil; Urbich, Carmen; Biswas, Subhra K; Murdoch, Craig; Plate, Karl H; Reiss, Yvonne; Lewis, Claire E

    2010-07-01

    TIE2-expressing monocytes/macrophages (TEM) are a highly proangiogenic subset of myeloid cells in tumors. Here, we show that circulating human TEMs are already preprogrammed in the circulation to be more angiogenic and express higher levels of such proangiogenic genes as matrix metalloproteinase-9 (MMP-9), VEGFA, COX-2, and WNT5A than TIE2(-) monocytes. Additionally, angiopoietin-2 (ANG-2) markedly enhanced the proangiogenic activity of TEMs and increased their expression of two proangiogenic enzymes: thymidine phosphorylase (TP) and cathepsin B (CTSB). Three "alternatively activated" (or M2-like) macrophage markers were also upregulated by ANG-2 in TEMs: interleukin-10, mannose receptor (MRC1), and CCL17. To investigate the effects of ANG-2 on the phenotype and function of TEMs in tumors, we used a double-transgenic (DT) mouse model in which ANG-2 was specifically overexpressed by endothelial cells. Syngeneic tumors grown in these ANG-2 DT mice were more vascularized and contained greater numbers of TEMs than those in wild-type (WT) mice. In both tumor types, expression of MMP-9 and MRC1 was mainly restricted to tumor TEMs rather than TIE2(-) macrophages. Furthermore, tumor TEMs expressed higher levels of MRC1, TP, and CTSB in ANG-2 DT tumors than WT tumors. Taken together, our data show that although circulating TEMs are innately proangiogenic, exposure to tumor-derived ANG-2 stimulates these cells to exhibit a broader, tumor-promoting phenotype. As such, the ANG-2-TEM axis may represent a new target for antiangiogenic cancer therapies. PMID:20530679

  19. Flow cytometric characterization of rat thymus cells in a radiation-dominated model of combined injury

    SciTech Connect

    Kaffenberger, W.; Gruber, D.F.; MacVittie, T.J.

    1988-05-01

    Thymuses of rats that had been: a) gamma-irradiated (500 cGy whole-body radiation (R)), or b) thermally injured (20% BSA dorsal, scald burn (TI)), or c) combined injured (irradiation followed by burn (CI)) were studied for involution and recovery processes after sublethal treatments. The expression of surface antigens on thymic cells before and after injuries was evaluated using the monoclonal antibodies (mcAB) MRC OX4, MRC OX7, MRC OX8, W3/13 HLK, and W3/25 and flow cytometric analysis. Thymic cellularity decreased to less than 1% of normal (N), age-matched rats by 4 days after R or CI. Recovery reached 60% to 70% of N by 28 days post treatments. TI caused a biphasic thymic recovery pattern with nadirs of 40% of N on days 7 and 21. Recovery at day 28 was similar to that after R and CI. Expression of OX7, OX8, W3/13, and W3/25 antigens all reached nadirs of 40% of N by day 4 after R and CI. Recovery of antigen expression, except for W3/25, was near completion by day 7 after R and CI. Changes in antigen expression after TI were less pronounced for all mcAB tested. Decreases in labeling of thymocytes with the helper T-cell marker, W3/25, observed after TI, could not be correlated with elevated expressions of the suppressor/cytotoxic T-lymphocyte antigen, OX8. Variations in relative labeling of nonlymphoid thymic cells with OX4 (Ia-antigen) reflected the disappearance and recovery of radiosensitive lymphoid thymocytes. The similarity of results after R and CI demonstrate that the model of CI is radiation-dominated. The addition of burn injury to radiation trauma had no synergistically damaging effect on the parameters studied.

  20. 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.

  1. 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

  2. Microbial reverse electrodialysis cells for synergistically enhanced power production.

    PubMed

    Kim, Younggy; Logan, Bruce E

    2011-07-01

    A new type of bioelectrochemical system for producing electrical power, called a microbial reverse-electrodialysis cell (MRC), was developed to increase voltages and power densities compared to those generated individually by microbial fuel cells (MFCs) or reverse electrodialysis (RED) systems. In RED systems, electrode overpotentials create significant energy losses due to thermodynamically unfavorable electrode reactions, and therefore a large number of stacked cells must be used to have significant energy recovery. This results in high capital costs for the large number of membranes, and increases energy losses from pumping water through a large number of cells. In an MRC, high overpotentials are avoided through oxidation of organic matter by exoelectrogenic bacteria on the anode and oxygen reduction on the cathode. An MRC containing only five pairs of RED cells, fed solutions typical of seawater (600 mM NaCl) and river water (12 mM NaCl) at 0.85 mL/min, produced up to 3.6 W/m(2) (cathode surface area) and 1.2-1.3 V with acetate as a substrate. Pumping accounted for <2% of the produced power. A higher flow rate (1.55 mL/min) increased power densities up to 4.3 W/m(2). COD removal was 98% with a Coulombic efficiency of 64%. Power production by the individual components was substantially lower with 0.7 W/m(2) without salinity driven energy, and <0.015 W/m(2) with reduced exoelectrogenic activity due to substrate depletion. These results show that the combination of an MFC and a RED stack synergistically increases performance relative to the individual systems, producing a new type of system that can be used to more efficiently capture salinity driven energy from seawater and river water. PMID:21644573

  3. Superior rectus transposition combined with medial rectus recession for Duane syndrome and sixth nerve palsy

    PubMed Central

    Mehendale, Reshma A.; Dagi, Linda R.; Wu, Carolyn; Ledoux, Danielle; Johnston, Suzanne; Hunter, David G.

    2013-01-01

    Objective Vertical rectus transposition (VRT) is used to treat abduction limitation, but new vertical deviations and anterior segment ischemia are concerns. Johnston and Crouch described superior rectus transposition (SRT), a procedure in which only the superior rectus muscle is transposed temporally. We describe our results using augmented temporal SRT with adjustable medial rectus muscle recession (MRc) for treatment of Duane syndrome I (DS) and sixth nerve palsy. Methods Retrospective surgical case review of patients undergoing the SRT procedure. Pre- and post-operative orthoptic measurements were recorded. Minimum follow-up was 6 weeks. Main outcome measures included angle of esotropia in primary position and the angle of head turn. Secondary outcomes included duction limitation, stereopsis, and new vertical deviations. Results The review identified seventeen patients (10 with DS and 7 with sixth nerve palsy). SRT+MRc improved esotropia [from 44 PD to 10.1 PD (p< 0.0001)], reduced abduction limitation [from −4.3 to −2.7 (p<0.0001)] and improved compensatory head posture [from 28°to 4° (p<0.0001)]. Stereopsis was recovered in eight patients (p=0.03). Three patients required a reoperation; one for overcorrection and 2 for undercorrection. A new primary position vertical deviation was observed in 2/7 patients with complex sixth nerve palsy and 0/10 DS patients. No patient described torsional diplopia. Conclusions SRT allows for the option of simultaneous medial rectus recession in patients with severe abduction imitation who require transposition surgery. SRT+MRc improved esotropia, head position, abduction limitation, and stereopsis without inducing torsional diplopia. PMID:22332212

  4. 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

  5. Tethering of SCFDia2 to the Replisome Promotes Efficient Ubiquitylation and Disassembly of the CMG Helicase

    PubMed Central

    Maculins, Timurs; Nkosi, Pedro Junior; Nishikawa, Hiroko; Labib, Karim

    2015-01-01

    Summary Disassembly of the Cdc45-MCM-GINS (CMG) DNA helicase, which unwinds the parental DNA duplex at eukaryotic replication forks, is the key regulated step during replication termination but is poorly understood [1, 2]. In budding yeast, the F-box protein Dia2 drives ubiquitylation of the CMG helicase at the end of replication, leading to a disassembly pathway that requires the Cdc48 segregase [3]. The substrate-binding domain of Dia2 comprises leucine-rich repeats, but Dia2 also has a TPR domain at its amino terminus that interacts with the Ctf4 and Mrc1 subunits of the replisome progression complex [4, 5], which assembles around the CMG helicase at replication forks [6]. Previous studies suggested two disparate roles for the TPR domain of Dia2, either mediating replisome-specific degradation of Mrc1 and Ctf4 [4] or else tethering SCFDia2 (SCF [Skp1/cullin/F-box protein]) to the replisome to increase its local concentration at replication forks [5]. Here, we show that SCFDia2 does not mediate replisome-specific degradation of Mrc1 and Ctf4, either during normal S phase or in response to replication stress. Instead, the tethering of SCFDia2 to the replisome progression complex increases the efficiency of ubiquitylation of the Mcm7 subunit of CMG, both in vitro and in vivo. Correspondingly, loss of tethering reduces the efficiency of CMG disassembly in vivo and is synthetic lethal in combination with a disassembly-defective allele of CDC48. Residual ubiquitylation of Mcm7 in dia2-ΔTPR cells is still CMG specific, highlighting the complex regulation of the final stages of chromosome replication, about which much still remains to be learned. PMID:26255844

  6. 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

  7. Exploring the impact of mask making constraints on double patterning design rules

    NASA Astrophysics Data System (ADS)

    Dam, Thuc; Sinn, Robert; Rissman, Paul; Gleason, Bob

    2011-11-01

    In order to achieve an economical design-to-mask (DTM) development cycle in the low k1 domain, designers, lithographers, and mask makers needed to move away from many sequentially isolated developmental activities onto one collaborative environment managed by a computational lithography platform that integrates their respective ecosystems. 1,2 A successful development cycle used to be achievable by designers providing designs to lithographers, who then provided RET/OPC solutions to realize designs, but once k1 fell below a certain level, the lithographers could not provide solutions to realize some critical designs, which then required feedback to designers for further redesigns requiring further lithographic evaluation cycles. So collaboration and automations between lithographers and designers became necessary to reduce feedback loops and development cycle time. RET and design solutions also were impacted by mask making, and so mask maker's feedback on MRC and other constraints needed to be integrated for all three groups to achieve an economical DTM. As many lithographers attempted to print sub-80 nm pitches with 193 nm wavelength, it became necessary to use double patterning to achieve feature resolution. With the effective pitch doubling on each split layer, there could be significant increased design rule freedom for certain complex design situations. Using an integrated computational lithographic platform, one could find design space sweet spots that could further achieve optimal lithographic performance. In this paper, the optimization of design rules (DRD) for double pattern designs (~60 nm pitch) was explored with the mask maker's perspective. The experiment to be presented started with a 2x nm design set of clips. Each set of clips underwent size/width/space/pitch variations to generate a design space, and then each design space underwent SMO with an inverse lithography technology (ILT) engine using various mask MRC's and manhattan segmentations. The

  8. 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. PMID:26724375

  9. 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.

  10. Antimalarial efficacy of Albizia lebbeck (Leguminosae) against Plasmodium falciparum in vitro & P. berghei in vivo

    PubMed Central

    Kalia, Shagun; Walter, Neha Sylvia; Bagai, Upma

    2015-01-01

    Background & objectives: Albizia lebbeck Benth. (Leguminosae) has long been used in Indian traditional medicine. The current study was designed to test antimalarial activity of ethanolic bark extract of A. lebbeck (EBEAL). Methods: EBEAL was prepared by soxhlet extraction and subjected to phytochemical analysis. The extract was evaluated for its in vitro antimalarial activity against Plasmodium falciparum chloroquine (CQ) sensitive (MRC2) and CQ resistant (RKL9) strains. Cytotoxicity (CC50) of extract against HeLa cells was evaluated. Median lethal dose (LD50) was determined to assess safety of EBEAL in BALB/c mice. Schizonticidal (100-1000 mg/kg) and preventive (100-750 mg/kg) activities of EBEAL were evaluated against P. berghei. Curative activity (100-750 mg/kg) of extract was also evaluated. Results: Phytochemical screening revealed presence of alkaloids, flavonoids, phenols, saponins, terpenes and phytosterols. The extract exhibited IC50 of 8.2 μg/ml (MRC2) and 5.1 μg/ml (RKL9). CC50 of extract on HeLa cell line was calculated to be >1000 μg/ml. EBEAL showed selectivity indices (SI) of >121.9 and >196.07 against MRC2 and RKL9 strains of P. falciparum, respectively. LD50 of EBEAL was observed to be >5 g/kg. Dose-dependent chemosuppression was observed with significant (P<0.001) schizonticidal activity at 1000 mg/kg with ED50 >100 mg/kg. Significant (P<0.001) curative and repository activities were exhibited by 750 mg/kg concentration of extract on D7. Interpretation & conclusions: The present investigation reports antiplasmodial efficacy of EBEAL in vitro against P. falciparum as evident by high SI values. ED50 of <100 mg/kg against P. berghei categorizes EBEAL as active antimalarial. Further studies need to be done to exploit its antiplasmodial activity further. PMID:26905234

  11. 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

  12. Morphological responses of mitochondria-rich cells to hypersaline environment in the Australian mudskipper, Periophthalmus minutus.

    PubMed

    Itoki, Naoko; Sakamoto, Tatsuya; Hayashi, Masahiro; Takeda, Tatsusuke; Ishimatsu, Atsushi

    2012-07-01

    A population of the Australian mudskipper, Periophthalmus minutus, was found to inhabit mudflat that remained uncovered by tide for more than 20 days in some neap tides. During these prolonged emersion periods, P. minutus retreated into burrows containing little water, with a highest recorded salinity of 84 ± 7.4 psu (practical salinity unit). To explore the mechanical basis for this salinity tolerance in P. minutus, we determined the densities of mitochondria-rich cells (MRCs) in the inner and outer opercula and the pectoral fin skin, in comparison with P. takita, [corrected] from an adjacent lower intertidal habitat, and studied morphological responses of MRCs to exposure to freshwater (FW), and 100% (34-35 psu) and 200% seawater (SW). Periophthalmus minutus showed a higher density of MRCs in the inner operculum (3365 ± 821 cells mm(-2)) than in the pectoral fin skin (1428 ± 161) or the outer operculum (1100 ± 986), all of which were higher than the MRC densities in p. takita. [corrected]. No mortality occurred in 100% or 200% SW, but half of the fish died within four days in FW. Neither 200% SW nor FW exposure affected MRC density. Transfer to 200% SW doubled MRC size after 9-14 days with no change in the proportion of MRCs with apical pits or plasma sodium concentration. In contrast, transfer to FW resulted in a rapid closing of pits and a significant reduction in plasma sodium concentration. These results suggest that P. minutus has evolved morphological and physiological mechanisms to withstand hypersaline conditions that they may encounter in their habitat. PMID:22775253

  13. 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.

  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. 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

  16. 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.

  17. Transplantations in adult acute lymphoblastic leukemia--grounds for optimism?

    PubMed

    Goldstone, Anthony H

    2009-01-01

    The large MRC/ECOG Adult Acute Lymphoblastic Leukemia Study establishes the value of sibling donor allogeneic transplantation in patients with standard risk, demonstrating superior outcome to conventional chemotherapy. The small but significant number of patients having matched unrelated donor transplantations on this study protocol appear to do well and might establish the value of such an approach for those without a sibling. Reduced-intensity conditioning might begin to address the transplantation-related mortality problems of the older patients. The youngest adults might not need to undergo transplantation at all. If they are now treated on pediatric chemotherapy protocols, their outcome appears to improve significantly. PMID:19778843

  18. Theory of Change: a theory-driven approach to enhance the Medical Research Council's framework for complex interventions

    PubMed Central

    2014-01-01

    Background The Medical Research Councils’ framework for complex interventions has been criticized for not including theory-driven approaches to evaluation. Although the framework does include broad guidance on the use of theory, it contains little practical guidance for implementers and there have been calls to develop a more comprehensive approach. A prospective, theory-driven process of intervention design and evaluation is required to develop complex healthcare interventions which are more likely to be effective, sustainable and scalable. Methods We propose a theory-driven approach to the design and evaluation of complex interventions by adapting and integrating a programmatic design and evaluation tool, Theory of Change (ToC), into the MRC framework for complex interventions. We provide a guide to what ToC is, how to construct one, and how to integrate its use into research projects seeking to design, implement and evaluate complex interventions using the MRC framework. We test this approach by using ToC within two randomized controlled trials and one non-randomized evaluation of complex interventions. Results Our application of ToC in three research projects has shown that ToC can strengthen key stages of the MRC framework. It can aid the development of interventions by providing a framework for enhanced stakeholder engagement and by explicitly designing an intervention that is embedded in the local context. For the feasibility and piloting stage, ToC enables the systematic identification of knowledge gaps to generate research questions that strengthen intervention design. ToC may improve the evaluation of interventions by providing a comprehensive set of indicators to evaluate all stages of the causal pathway through which an intervention achieves impact, combining evaluations of intervention effectiveness with detailed process evaluations into one theoretical framework. Conclusions Incorporating a ToC approach into the MRC framework holds promise for

  19. Replication and Active Partition of Integrative and Conjugative Elements (ICEs) of the SXT/R391 Family: The Line between ICEs and Conjugative Plasmids Is Getting Thinner.

    PubMed

    Carraro, Nicolas; Poulin, Dominique; Burrus, Vincent

    2015-06-01

    Integrative and Conjugative Elements (ICEs) of the SXT/R391 family disseminate multidrug resistance among pathogenic Gammaproteobacteria such as Vibrio cholerae. SXT/R391 ICEs are mobile genetic elements that reside in the chromosome of their host and eventually self-transfer to other bacteria by conjugation. Conjugative transfer of SXT/R391 ICEs involves a transient extrachromosomal circular plasmid-like form that is thought to be the substrate for single-stranded DNA translocation to the recipient cell through the mating pore. This plasmid-like form is thought to be non-replicative and is consequently expected to be highly unstable. We report here that the ICE R391 of Providencia rettgeri is impervious to loss upon cell division. We have investigated the genetic determinants contributing to R391 stability. First, we found that a hipAB-like toxin/antitoxin system improves R391 stability as its deletion resulted in a tenfold increase of R391 loss. Because hipAB is not a conserved feature of SXT/R391 ICEs, we sought for alternative and conserved stabilization mechanisms. We found that conjugation itself does not stabilize R391 as deletion of traG, which abolishes conjugative transfer, did not influence the frequency of loss. However, deletion of either the relaxase-encoding gene traI or the origin of transfer (oriT) led to a dramatic increase of R391 loss correlated with a copy number decrease of its plasmid-like form. This observation suggests that replication initiated at oriT by TraI is essential not only for conjugative transfer but also for stabilization of SXT/R391 ICEs. Finally, we uncovered srpMRC, a conserved locus coding for two proteins distantly related to the type II (actin-type ATPase) parMRC partitioning system of plasmid R1. R391 and plasmid stabilization assays demonstrate that srpMRC is active and contributes to reducing R391 loss. While partitioning systems usually stabilizes low-copy plasmids, srpMRC is the first to be reported that stabilizes a

  20. Replication and Active Partition of Integrative and Conjugative Elements (ICEs) of the SXT/R391 Family: The Line between ICEs and Conjugative Plasmids Is Getting Thinner

    PubMed Central

    Carraro, Nicolas; Poulin, Dominique; Burrus, Vincent

    2015-01-01

    Integrative and Conjugative Elements (ICEs) of the SXT/R391 family disseminate multidrug resistance among pathogenic Gammaproteobacteria such as Vibrio cholerae. SXT/R391 ICEs are mobile genetic elements that reside in the chromosome of their host and eventually self-transfer to other bacteria by conjugation. Conjugative transfer of SXT/R391 ICEs involves a transient extrachromosomal circular plasmid-like form that is thought to be the substrate for single-stranded DNA translocation to the recipient cell through the mating pore. This plasmid-like form is thought to be non-replicative and is consequently expected to be highly unstable. We report here that the ICE R391 of Providencia rettgeri is impervious to loss upon cell division. We have investigated the genetic determinants contributing to R391 stability. First, we found that a hipAB-like toxin/antitoxin system improves R391 stability as its deletion resulted in a tenfold increase of R391 loss. Because hipAB is not a conserved feature of SXT/R391 ICEs, we sought for alternative and conserved stabilization mechanisms. We found that conjugation itself does not stabilize R391 as deletion of traG, which abolishes conjugative transfer, did not influence the frequency of loss. However, deletion of either the relaxase-encoding gene traI or the origin of transfer (oriT) led to a dramatic increase of R391 loss correlated with a copy number decrease of its plasmid-like form. This observation suggests that replication initiated at oriT by TraI is essential not only for conjugative transfer but also for stabilization of SXT/R391 ICEs. Finally, we uncovered srpMRC, a conserved locus coding for two proteins distantly related to the type II (actin-type ATPase) parMRC partitioning system of plasmid R1. R391 and plasmid stabilization assays demonstrate that srpMRC is active and contributes to reducing R391 loss. While partitioning systems usually stabilizes low-copy plasmids, srpMRC is the first to be reported that stabilizes a

  1. 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

  2. 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

  3. Synthesis, characterization and biological activity of three square-planar complexes of Ni(II) with ethyl (2E)-2-[2-(diphenylphosphino)benzylidene]hydrazinecarboxylate and monodentate pseudohalides.

    PubMed

    Milenković, Milica; Bacchi, Alessia; Cantoni, Giulia; Vilipić, Jovana; Sladić, Dušan; Vujčić, Miroslava; Gligorijević, Nevenka; Jovanović, Katarina; Radulović, Siniša; Anđelković, Katarina

    2013-10-01

    Three square-planar complexes of nickel(II) with the tridentate condensation derivative of 2-(diphenylphosphino)benzaldehyde and ethyl carbazate, and monodentate pseudohalides, have been synthesized. Their crystal structures have been determined. All the complexes showed a significant antifungal activity, while only the azido complex displayed antibacterial activity. All the complexes were cytotoxic to a panel of six tumor cell lines, the azido complex showing a similar activity as cisplatin to leukemia cell line K562 and lower toxicity to normal MRC-5 cells than that anticancer agent. The complexes interfered with cell cycle of tumor cells and induced plasmid DNA cleavage. PMID:23973823

  4. BER Performance for Downlink MC-CDMA Systems over Rician Fading Channels

    NASA Astrophysics Data System (ADS)

    Hou, Zhihua; Dubey, Vimal K.

    2005-12-01

    We consider downlink multicarrier code-division multiple-access (MC-CDMA) systems using binary phase-shift keying (BPSK) modulation scheme and maximal ratio combining (MRC) in frequency-selective Rician fading channels. A time-domain method to obtain bit error rate (BER) by calculating moment generating function (MGF) of the decision variable for a tapped-delay-line channel model is proposed. This method does not require any assumption regarding the statistical or spectral distribution of multiple access interference (MAI), and it is also not necessary to assume that the fading encountered by the subcarriers is independent of each other. The analytical formula is also verified by simulations.

  5. Three-dimensional mammalian cell growth on nonwoven polyester fabric disks.

    PubMed

    Petti, S A; Lages, A C; Sussman, M V

    1994-01-01

    Small disks of nonwoven polyester fabric (NWPF), similar to Fibra-Cel carriers, were surface treated with strong acid and used as a high surface area support matrix for in vitro culture of anchorage dependent MRC-5 cells. The disks can be autoclaved, and require inocula concentrations of only 2-5% of the final cell densities, which have reached 10(8) cells/mL of disk bed volume. Scanning electron microscopy photographs shown herein reveal that cells grow in a multilayered fashion between the randomly arrayed fibers of the nonwoven fabric, emulating in vivo growth. PMID:7522468

  6. Hydroperoxy-cycloartane triterpenoids from the leaves of Markhamia lutea, a plant ingested by wild chimpanzees.

    PubMed

    Lacroix, Damien; Prado, Soizic; Deville, Alexandre; Krief, Sabrina; Dumontet, Vincent; Kasenene, John; Mouray, Elisabeth; Bories, Christian; Bodo, Bernard

    2009-07-01

    In the framework of the phytochemical investigation of plant species eaten by wild chimpanzees in their natural environment in Uganda, leaf samples of Markhamia lutea were selected and collected. The crude ethyl acetate extract of M. lutea leaves exhibited significant in vitro anti-parasitic activity and low cytotoxicity against MRC5 and KB cells. Fractionation of this extract led to six cycloartane triterpenoids, musambins A-C and their 3-O-xyloside derivatives musambiosides A-C. The structures were elucidated on the basis of spectral studies including mass spectroscopy and extensive 2D NMR. Most of the compounds exhibited mild anti-leishmanial and anti-trypanosomal activities. PMID:19679323

  7. 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.

  8. Treatment of chronic inflammatory demyelinating polyradiculoneuropathy with methotrexate

    PubMed Central

    Fialho, D; Chan, Y‐C; Allen, D C; Reilly, M M; Hughes, R A C

    2006-01-01

    We discovered many reports of other immunosuppressive drugs being used in adults with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but none of methotrexate. As weekly low dose oral methotrexate is safe, effective, and well tolerated in other diseases, we treated 10 patients with otherwise treatment resistant CIDP. Seven showed improvement in strength by at least two points on the MRC sum score and three worsened. Only two showed an improvement in disability and both were also receiving corticosteroids. We discuss the difficulty of detecting an improvement in treatment resistant CIDP and propose methotrexate as a suitable agent for testing in a randomised trial. PMID:16543541

  9. 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. PMID:26856364

  10. Haemoglobin D Punjab (D Los Angeles)

    PubMed Central

    Vella, F.; Lehmann, H.

    1974-01-01

    A search for haemoglobin variants undertaken in Canada revealed 21 unrelated instances of Hb D Punjab amongst 207,300 specimens tested. Of these, eight came from East Indian immigrants and the rest from Canadians of United Kingdom origin. No instances of Hb D Punjab were found in 14,500 specimens from Canadian Indians that were tested. The geographical origins of 27 instances of Hb D Punjab characterized at the MRC Abnormal Haemoglobin Unit, Cambridge are presented. Of these five were natives of the British Isles. The results of surveys undertaken in the United Kingdom are summarized. The global distribution of Hb D Punjab is discussed. PMID:4613830