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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. 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.

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

    NASA Astrophysics Data System (ADS)

    Gulliford, Sarah L.

    2014-03-01

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

  4. 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. [Confusion about MRC dyspnea scales in Japan--which MRC dyspnea scale should we employ?].

    PubMed

    Miyamoto, Kenji

    2008-08-01

    Though the Hugh-Jones dyspnea scale has been widely used in Japan, the British Medical Research Council (MRC) dyspnea scale and/or modified MRC dyspnea scales have been used in many other countries. One of these modified MRC dyspnea scales was translated into Japanese and appeared in both the "Japanese Manual of Respiratory Rehabilitation (2003)" and the "Japanese Standards for the Diagnosis and Care of Patients with Chronic Obstructive Pulmonary Disease (2004)" which were published by the Japanese Respiratory Society. Subsequently, the MRC dyspnea scale appeared in a textbook and in review articles published in Japan. However, this dyspnea scale, which was translated into Japanese, is not used by the British Thoracic Society, American Thoracic Society, European Respiratory Society, Canadian Respiratory Society, or Global Initiative for Chronic Obstructive Lung Disease (GOLD). The Japanese version of the MRC dyspnea scale has two serious problems: 1) normal healthy subjects have to be classified into dyspnea grade 0 or grade 1, and 2) incorrect Japanese translation of the scale. The Japanese Respiratory Society has to decide which MRC dyspnea scale should be employed, with a well-thought-out translation.

  6. MRC for compression of Blake Archive images

    NASA Astrophysics Data System (ADS)

    Misic, Vladimir; Kraus, Kari; Eaves, Morris; Parker, Kevin J.; Buckley, Robert R.

    2002-11-01

    The William Blake Archive is part of an emerging class of electronic projects in the humanities that may be described as hypermedia archives. It provides structured access to high-quality electronic reproductions of rare and often unique primary source materials, in this case the work of poet and painter William Blake. Due to the extensive high frequency content of Blake's paintings (namely, colored engravings), they are not suitable for very efficient compression that meets both rate and distortion criteria at the same time. Resolving that problem, the authors utilized modified Mixed Raster Content (MRC) compression scheme -- originally developed for compression of compound documents -- for the compression of colored engravings. In this paper, for the first time, we have been able to demonstrate the successful use of the MRC compression approach for the compression of colored, engraved images. Additional, but not less important benefits of the MRC image representation for Blake scholars are presented: because the applied segmentation method can essentially lift the color overlay of an impression, it provides the student of Blake the unique opportunity to recreate the underlying copperplate image, model the artist's coloring process, and study them separately.

  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. A new method of ICCD imaging system MRC measurement

    NASA Astrophysics Data System (ADS)

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

    2005-02-01

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

  9. 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.

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

    PubMed Central

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

    2016-01-01

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

  11. Series solutions for π/4-DQPSK BER with MRC

    NASA Astrophysics Data System (ADS)

    Chandra, Aniruddha; Bose, Chayanika

    2012-03-01

    Simple series expressions for bit error rate (BER) of π/4 shifted differential quaternary phase-shift keying (π/4-DQPSK) over some common fading environments (Rayleigh, Rician and Nakagami-m) are derived. Both single- and multi-channel reception scenarios are considered. In case of multi-antenna reception, it is assumed that the fading is independent and identically distributed (IID), and the receiver follows optimum maximal ratio combining (MRC). The derived expressions, computed through probability density function (PDF)-based approach, give an exact match with moment-generating function (MGF)-based solutions but get rid of numerical integrations involved in MGF approach. Further, the analytical results presented in this article consist of finite or rapidly converging infinite series and thus a trade-off between precision and complexity can be easily realised by choosing a specific number of terms. Bounds on the error resulting from truncation of the infinite series are also derived. Moreover, it was shown that the series solutions, when reasonably truncated, still provide better approximations than the previous attempts.

  12. Investigation of the bystander effect in MRC5 cells after acute and fractionated irradiation in vitro.

    PubMed

    Soleymanifard, Shokouhozaman; Toossi, Mohammad Taghi Bahreyni; Samani, Roghayeh Kamran; Mohebbi, Shokoufeh

    2014-04-01

    Radiation-induced bystander effect (RIBE) has been defined as radiation responses observed in nonirradiated cells. It has been the focus of investigators worldwide due to the deleterious effects it induces in nonirradiated cells. The present study was performed to investigate whether acute or fractionated irradiation will evoke a differential bystander response in MRC5 cells. A normal human cell line (MRC5), and a human lung tumor cell line (QU-DB) were exposed to 0, 1, 2, and 4Gy of single acute or fractionated irradiation of equal fractions with a gap of 6 h. The MRC5 cells were supplemented with the media of irradiated cells and their micronucleus frequency was determined. The micronucleus frequency after single and fractionated irradiation did not vary significantly in the MRC5 cells conditioned with autologous or QU-DB cell-irradiated media, except for 4Gy where the frequency of micronucleated cells was lower in those MRC5 cells cultured in the media of QU-DB-exposed with a single dose of 4Gy. Our study demonstrates that the radiation-induced bystander effect was almost similar after single acute and fractionated exposure in MRC5 cells.

  13. Performance analysis of MRC spatial diversity receiver system for satellite-to-ground downlink optical transmissions

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

    The performances of satellite-to-ground downlink optical communications over Gamma-Gamma distributed turbulence are studied for multiple apertures receiver system. Maximum ratio combining (MRC) technique is considered as a combining scheme to mitigate the atmospheric turbulence under thermal noise limited conditions. Bit-error rate (BER) performances for on-off keying (OOK) modulated direct detection optical communications are analyzed for MRC diversity receptions through an approximation method. To show the net diversity gain of multiple apertures receiver system, BER performances of MRC receiver system are compared with a single monolithic aperture receiver system with the same total aperture area (same average total incident optical power) for satellite-to-ground downlink optical communications. All the numerical results are also verified by Monte-Carlo (MC) simulations.

  14. Automobile exhaust particle-induced apoptosis and necrosis in MRC-5 cells.

    PubMed

    Zhao, X H; Wang, X L; Li, X Y

    2001-05-31

    To study the effect of particulate extracts (PE) collected from a heavy traffic road in Lanzhou City, on MRC-5 cell apoptosis, and to explore the toxicity action of PE and its mechanism. Cultured MRC-5 cells were incubated in the extracts of different concentrations. Inhibition of proliferation was measured with a colorimetric 3-[4,5-dimethyl thiazol-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assay. Morphological assessment of apoptosis was performed with fluorescence microscopy and electronic microscopy. Extracted DNA from the cells was electrophoresed on agarose gel in order to observe DNA fragmentation. The amount of apoptotic cells was measured by flow cytometry. The results indicated that exposure of exponentially growing MRC-5 cells exposed to PE 5-160 microg l(-1) for 24-96 h resulted in dose- and time-dependent reduction of survival of MRC-5 cells. After treatment with PE, markedly morphological changes of MRC-5 cells including "apoptotic bodies", were observed with a fluorescence microscope. Agarose gel electrophoresis of DNA from the cells treated with PE for 48 and 72 h revealed a "ladder" pattern. PE induced apoptosis in low doses but necrosis in high doses. Apoptotic rates were 12.95, 17.40 and 29.80% after treatment with PE 5, 10, and 20 microg l(-1), respectively. A typical sub-diploid apoptosis peak was demonstrated in MRC-5 cells treated with PE. A significant dose-effect response and time-effect correlation could be found between apoptosis rates and PE. All results confirmed that the PE could induce and accelerate apoptosis in low doses but necrosis in high doses.

  15. Tolerance-based OPC and solution to MRC-constrained OPC

    NASA Astrophysics Data System (ADS)

    Ping, Yang; Li, Xiaohai; Jang, Stephen; Kwa, Denny; Zhang, Yunqiang; Lugg, Robert

    2011-04-01

    Model based optical proximity correction (MB-OPC) has been widely used in advanced lithography process today. However controlling the edge placement error (EPE) and critical dimension (CD) has become harder as the k1 process factor decreases and design complexity increases. Especially, for high-NA lithography using strong off-axis illumination (OAI), ringing effects on 2D layout makes CD control difficult. In addition, mask rule check (MRC) limits also prevent good OPC convergence where two segment edges are corrected towards each other to form a correction-conflicting scenario because traditional OPC only consider the impact of the current edge when calculating the edge movement. A more sophisticated OPC algorithm that considers the interaction between segments is necessary to find a solution that is both MRC and convergence compliant. This paper first analyzes the phenomenon of MRC-constrained OPC. Then two multiple segment correction techniques for tolerance-based OPC and MRC-constrained OPC are discussed. These correction techniques can be applied to selected areas with different lithographic specifications. The feasibility of these techniques is demonstrated by quantifying the EPE convergence through iterations and by comparing the simulated contour results.

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

    NASA Astrophysics Data System (ADS)

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

    2006-10-01

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

  17. 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

  18. Outage Capacity Analysis of TAS/MRC Systems over Arbitrary Nakagami-m Fading Channels

    NASA Astrophysics Data System (ADS)

    Hung, Chia-Chun; Chiang, Ching-Tai; Lin, Shyh-Neng; Wu, Rong-Ching

    A simple closed-form approximation for the outage capacity of Transmit Antenna Selection/Maximal-Ratio Combining (TAS/MRC) systems over independent and identically distributed (i.i.d) Nakagami-m fading channels is derived while the fading index is a positive integer. When the Nakagami-m fading index is not an integer, the approximate outage capacity is derived as a single infinite series of Gamma function. Computer simulations verify the accuracy of the approximate results.

  19. Protein crystallization screens developed at the MRC Laboratory of Molecular Biology.

    PubMed

    Gorrec, Fabrice

    2016-05-01

    In order to solve increasingly challenging protein structures with crystallography, crystallization reagents and screen formulations are regularly investigated. Here, we briefly describe 96-condition screens developed at the MRC Laboratory of Molecular Biology: the LMB sparse matrix screen, Pi incomplete factorial screens, the MORPHEUS grid screens and the ANGSTROM optimization screen. In this short review, we also discuss the difficulties and advantages associated with the development of protein crystallization screens.

  20. Inverse lithography technology (ILT): keep the balance between SRAF and MRC at 45 and 32 nm

    NASA Astrophysics Data System (ADS)

    Pang, Linyong; Liu, Yong; Dam, Thuc; Mihic, Kresimir; Cecil, Thomas; Abrams, Dan

    2007-10-01

    In this paper, we present the Luminescent's ILT approach that can rapidly solve for the optimal photomask design. We will discuss the latest development of ILT at Luminescent in the areas of sub-resolution assist feature (SRAF) generation and optimization to improve process window, and mask rule compliance (MRC). Results collected internally and from customers demonstrate that ILT is not only an R&D tool, but also a tool quickly maturing for production qualification at advanced technology nodes. By enforcing the proper constraints while optimizing the masks, ILT can improve process windows while maintaining mask costs at a reasonable level.

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

    PubMed Central

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

    1982-01-01

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

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

    PubMed

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

    1982-12-01

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

  3. 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

  4. Error Probability of MRC in Frequency Selective Nakagami Fading in the Presence of CCI and ACI

    NASA Astrophysics Data System (ADS)

    Rahman, Mohammad Azizur; Sum, Chin-Sean; Funada, Ryuhei; Sasaki, Shigenobu; Baykas, Tuncer; Wang, Junyi; Harada, Hiroshi; Kato, Shuzo

    An exact expression of error rate is developed for maximal ratio combining (MRC) in an independent but not necessarily identically distributed frequency selective Nakagami fading channel taking into account inter-symbol, co-channel and adjacent channel interferences (ISI, CCI and ACI respectively). The characteristic function (CF) method is adopted. While accurate analysis of MRC performance cannot be seen in frequency selective channel taking ISI (and CCI) into account, such analysis for ACI has not been addressed yet. The general analysis presented in this paper solves a problem of past and present interest, which has so far been studied either approximately or in simulations. The exact method presented also lets us obtain an approximate error rate expression based on Gaussian approximation (GA) of the interferences. It is shown, especially while the channel is lightly faded, has fewer multipath components and a decaying delay profile, the GA may be substantially inaccurate at high signal-to-noise ratio. However, the exact results also reveal an important finding that there is a range of parameters where the simpler GA is reasonably accurate and hence, we don't have to go for more involved exact expression.

  5. Outage Probability of MRC for κ-μ Shadowed Fading Channels under Co-Channel Interference

    PubMed Central

    Chen, Changfang; Shu, Minglei; Wang, Yinglong; Yang, Ming; Zhang, Chongqing

    2016-01-01

    In this paper, exact closed-form expressions are derived for the outage probability (OP) of the maximal ratio combining (MRC) scheme in the κ-μ shadowed fading channels, in which both the independent and correlated shadowing components are considered. The scenario assumes the received desired signals are corrupted by the independent Rayleigh-faded co-channel interference (CCI) and background white Gaussian noise. To this end, first, the probability density function (PDF) of the κ-μ shadowed fading distribution is obtained in the form of a power series. Then the incomplete generalized moment-generating function (IG-MGF) of the received signal-to-interference-plus-noise ratio (SINR) is derived in the closed form. By using the IG-MGF results, closed-form expressions for the OP of MRC scheme are obtained over the κ-μ shadowed fading channels. Simulation results are included to validate the correctness of the analytical derivations. These new statistical results can be applied to the modeling and analysis of several wireless communication systems, such as body centric communications. PMID:27851817

  6. 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

  7. Inhibition of connective tissue growth factor attenuates paraquat-induced lung fibrosis in a human MRC-5 cell line.

    PubMed

    Huang, Min; Yang, Huifang; Zhu, Lingqin; Li, Honghui; Zhou, Jian; Zhou, Zhijun

    2016-11-01

    Chronic exposure to Paraquat (PQ) may result in progressive pulmonary fibrosis and subsequent chronic obstructive pulmonary malfunction. Connective tissue growth factor (CTGF) has been proposed as a key determinant in the development of lung fibrosis. We investigated thus whether knock down of CTGF can prevent human lung fibroblasts (MRC-5) activation and proliferation with the subsequent inhibition of PQ-induced fibrosis. MRC-5 was transfected with CTGF-siRNAs and exposed to different concentrations of PQ. The siRNA-silencing efficacy was evaluated using western blotting analyses, qRT-PCR and flow cytometry. Next, the viability and migration of MRC-5 was determined. MMP-2, MMP-9, and TIMP-1 accumulation were quantified to evaluate the lung fibrosis exposure to PQ. Over expression of CTGF mRNA was observed in human MRC-5 cell as early as 6 h following PQ stimulation. CTGF gene expression in MRC-5 cells was substantially reduced by RNAi, which significantly suppressed the expression of the lung fibrosis markers such as tissue inhibitor of metalloproteinase-2 (TIMP-2), Matrix metalloproteinase-2 (MMP-2) and Matrix metalloproteinase-9 (MMP-9) that were stimulated by PQ. Inhibition of CTGF expression suppressed impeded the proliferation and migration ability of MRC-5 cells and resulted in cell-extracellular matrix (ECM) protein accumulation in cells. Our results suggest that CTGF promoted the development of PQ-induced lung fibrosis in collaboration with transforming growth factor β1 (TGFβ1). Furthermore, the observed arresting effects of CTGF knock down during this process suggested that CTGF is the potential target site for preventing PQ-induced pulmonary fibrosis. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1620-1626, 2016.

  8. RT-01FRACTIONATED STEREOTACTIC RADIOTHERAPY FOR PITUITARY ADENOMA WITH NOVALIS

    PubMed Central

    Arakawa, Yoshiki; Mizowaki, Takashi; Ogura, Kengo; Sakanaka, Katsuyuki; Hojo, Masato; Hiraoka, Masahiro; Miyamoto, Susumu; Murata, Daiki

    2014-01-01

    BACKGROUND: Radiation therapy is an available treatment modality for pituitary adenoma. In particular, it is effective for the case unable to be removed with surgery or repeating recurrence. However, hypopituitarism and optic nerve injury associated with radiation therapy become a problem. Novalis® (Brain Lab) is an equipment of radiation to establish the detailed irradiation area, fractionated stereotactic radiotherapy (fSRT) and intensity-modulated radiation therapy (IMRT). Retrospectively, we review local control and morbidity following fSRT with Novalis in pituitary adenoma. PATIENTS AND METHODS: Between 2007 and 2012, 29 patients with pituitary adenoma (9 functioning, 20 non-functioning) received fSRT with Novalis in our institute. Total radiation dose was 50.4-54Gy (1.8 Gy per fraction) and prescribed to the gross target volume + 2 mm. The effectiveness of fSRT was evaluated by tumor volume and clinical symptoms on pre- fSRT, and every 1-year. RESULTS: The median follow-up time was 59.1 months (20 to 83 months). Tumor regrowth was observed in 2 cases. Progression free survival rate was 93%. New visual field deficit was observed in 1 case, and new pituitary dysfunction were not observed in all patients. CONCLUSION: fSRT with Novalis is safe and effective in the treatment for pituitary adenoma. Although follow-up time is short, any problematic complications were not observed. In the future, fSRT is expected to make for safe and effective treatment in pituitary adenoma impossible to cure surgically.

  9. Evaluation of novel biodegradable cyclic carbonate polyester copolymers for cytocompatibility using MRC-5 cells.

    PubMed

    Longino, J; Mullen, B; Benghuzzi, H; Tucci, M; Tang, C; Storey, R; Puckett, A

    2003-01-01

    The objective of this work was to synthesize and characterize a novel series of biodegradable cyclic carbonate polyester copolymers based on lactide and 5-methyl-5-benzyloxy-carbonyl-1,3-dioxan-2-one (MBC). Two compositions were selected for characterization. One copolymer was based on a racemic mixture of 1-lactide with 15.4 mole % MBC and the other was based on 1-lactide with 8.2 mole % MBC. These polymers contain carboxylic acid moieties along the backbone that may be used for tethering bioactive agents, forming ionic crosslinks or be reacted with vinyl containing monomers to allow free radical crosslinking. The initial materials evaluated have the carboxylic acid functionalities blocked with benzene. These polymers and the de-blocked versions may have potential applications for hard and soft tissue scaffolds, control drug delivery matrixes or a variety of other applications in medicine. The copolymer samples were pressed into 7.0-mm diameter disk using a KBr press. The disks were then sterilized using U.V radiation under a laminar flow hood. After sterilization, the copolymer disks were submerged in 2 ml of media and placed in a CO2 regulated incubator at 37 degrees C. A total of six groups per phase (n = 7 test tubes per group) were used in this study. Test tubes in groups I and III were plated with MRC-5 and subsequently treated with media alone (controls). Test tubes in groups II and IV were plated with MRC-5 and subsequently treated with media before being introduced to copolymer samples. Cell number, as well as, biochemical markers such as protein and malondialdehyde (MDA) were determined at the end of the 24, 48 and 72-hour time periods. Representative test tubes were subjected to an H&E staining procedure for microscopic morphological evaluation. The results of this evaluation suggest that the exposure of both copolymers produced a non-cytotoxic environment with the MRC-5 cell line. Although both copolymers are non-cytotoxic, the sample having the higher

  10. Isolation of eastern equine encephalitis virus in A549 and MRC-5 cell cultures.

    PubMed

    Sotomayor, E A; Josephson, S L

    1999-07-01

    Eastern equine encephalitis (EEE) has been diagnosed either serologically or by virus isolation. Until now, the recovery of EEE virus has been delegated to reference laboratories with the expertise and resources needed to amplify the virus in a susceptible vertebrate host and/or to isolate and identify the virus in cell culture. We report a case in which EEE virus was recovered directly from a patient's cerebrospinal fluid in A549 and MRC-5 cell cultures. Many clinical virology laboratories routinely use these cells to recover adenovirus, herpes simplex virus, and enterovirus. To the best of our knowledge, this is the first report of isolation of EEE virus in A549 cell culture. This report demonstrates the possibility of recovery of EEE virus in cell culture without the necessity of bioamplification or maintaining unusual cell lines.

  11. Outage Probability and Ergodic Capacity of Spectrum-Sharing Systems with MRC Diversity

    NASA Astrophysics Data System (ADS)

    Jarrouj, Jiana; Blagojevic, Vesna; Ivanis, Predrag

    2016-03-01

    The spectrum sharing system employing maximum ratio combining (MRC) is analyzed in Nakagami fading environment, for the case when the interference from the primary user is present at the input of the secondary user receiver. The closed-form expressions for the probability density function of the signal-to-interference-and-noise ratio, the outage probability and the ergodic capacity of the SU link are derived under both peak interference and maximal transmit power constraints. Asymptotical expressions are provided for the important region where peak interference power constraint dominates and the case when the interference from the primary user's is dominant compared to the noise at the secondary user's receiver. The obtained expressions are presented for both cases of outdated and mean-value based power allocation and verified by using Monte Carlo simulation method.

  12. 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.

  13. 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.

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

    SciTech Connect

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

    2004-08-12

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

  15. 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

  16. MRC5 and QU-DB bystander cells can produce bystander factors and induce radiation bystander effect.

    PubMed

    Toossi, Mohammad Taghi Bahreyni; Mohebbi, Shokoufeh; Samani, Roghayeh Kamran; Soleymanifard, Shokouhozaman

    2014-07-01

    Radiation damages initiated by radiation-induced bystander effect (RIBE) are not limited to the first or immediate neighbors of the irradiated cells, but the effects have been observed in the cells far from the irradiation site. It has been postulated that bystander cells, by producing bystander factors, are actively involved in the propagation of bystander effect in the regions beyond the initial irradiated site. Current study was planned to test the hypothesis. MRC5 and QU-DB cell lines were irradiated, and successive medium transfer technique was performed to induce bystander effects in two bystander cell groups. Conditioned medium extracted from the target cells was transferred to the bystander cells (first bystander cells). After one hour, conditioned medium was substituted by fresh medium. Two hours later, the fresh medium was transferred to a second group of non-irradiated cells (second bystander cells). Micronucleated cells (MC) were counted to quantify damages induced in the first and second bystander cell groups. Radiation effect was observed in the second bystander cells as well as in the first ones. Statistical analyses revealed that the number of MC in second bystander subgroups was significantly more than the corresponding value observed in control groups, but in most cases it was equal to the number of MC observed in the first bystander cells. MRC5 and QU-DB bystander cells can produce and release bystander signals in the culture medium and affect non-irradiated cells. Therefore, they may contribute to the RIBE propagation.

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

    PubMed Central

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

    2016-01-01

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

  18. 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

  19. Genetic instability is prevented by Mrc1-dependent spatio-temporal separation of replicative and repair activities of homologous recombination

    PubMed Central

    Prado, Félix

    2014-01-01

    Homologous recombination (HR) is required to protect and restart stressed replication forks. Paradoxically, the Mrc1 branch of the S phase checkpoints, which is activated by replicative stress, prevents HR repair at breaks and arrested forks. Indeed, the mechanisms underlying HR can threaten genome integrity if not properly regulated. Thus, understanding how cells avoid genetic instability associated with replicative stress, a hallmark of cancer, is still a challenge. Here I discuss recent results that support a model by which HR responds to replication stress through replicative and repair activities that operate at different stages of the cell cycle (S and G2, respectively) and in distinct subnuclear structures. Remarkably, the replication checkpoint appears to control this scenario by inhibiting the assembly of HR repair centers at stressed forks during S phase, thereby avoiding genetic instability. PMID:24615940

  20. 1-Methyl-tryptophan attenuates regulatory T cells differentiation due to the inhibition of estrogen-IDO1-MRC2 axis in endometriosis

    PubMed Central

    Wei, Chunyan; Mei, Jie; Tang, Lingli; Liu, Yukai; Li, Dajin; Li, Mingqing; Zhu, Xiaoyong

    2016-01-01

    Foxp3+ regulatory T (Treg) cells contribute to the local dysfunctional immune environment in endometriosis, an estrogen-dependent gynecological disease, which affects the function of ectopic endometrial tissue clearance by the immune system. The reason for the high percentage of peritoneal Treg in endometriosis patients is unknown. Here, we show that the proportion of peritoneal Treg cells increases as endometriosis progresses. To determine the probable mechanism, we established a naive T cell-macrophage-endometrial stromal cell (ESC) co-culture system to mimic the peritoneal cavity microenvironment. After adding 1-methyl-tryptophan (1-MT), a specific inhibitor of indoleamine 2,3-dioxygenase-1 (IDO1), to the co-culture system, we found that the differentiation of Treg cells, mainly IL-10+ Treg cells, decreased. Therefore, 1-MT-pretreated ESCs-educated Treg cells performed impaired suppressive function. Moreover, estrogen promoted the differentiation of Treg cells by elevating IDO1 expression in the ectopic lesion. Subsequently, we examined mannose receptor C, type 2 (MRC2), which is an up-stream molecule of IL-10, by bioinformatics analysis and real-time PCR validation. MRC2 expression in ectopic ESCs was notably lower than that in normal ESCs, which further negatively regulated the expression of IDO1 and Ki-67 in ESCs. Furthermore, MRC2 is required for Treg differentiation in the ectopic lesion, especially that for CD4high Treg. Therefore, MRC2-silenced ESCs-educated Treg manifested a stronger suppressive function in vitro. Consistently, the percentage of Treg increased when MRC2-shRNA was administered in the peritoneal cavity of endometriosis-disease mice model. Besides, 1-MT improved the condition of endometriosis, in terms of reducing the number and weight of total ectopic lesions in vivo. These results indicate that the estrogen-IDO1-MRC2 axis participates in the differentiation and function of Treg and is involved in the development of endometriosis. Thus

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

    PubMed

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

    2000-04-10

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

  2. Halomethane-induced cytotoxicity and cell proliferation in human lung MRC-5 fibroblasts and NL20-TA epithelial cells.

    PubMed

    Nájera-Martínez, Minerva; García-Latorre, Ethel A; Reyes-Maldonado, Elba; Domínguez-López, M Lilia; Vega-López, Armando

    2012-09-01

    Halomethanes (HMs) can be formed during the chlorination process to obtain drinking water. In liver cells, HMs had been shown to be mutagenic and carcinogenic; however, their bioactivation by CYP 2E1 and GSTT1 is required. Although inhalation is the most common pathway of exposure, reports on the toxic effects induced by HMs in human lung are contradictory. The aim of this study was therefore to evaluate in vitro cytotoxicity and cell proliferation induced by CH(2)Cl(2), CHCl(3) and BrCHCl(2) in human lung NL20-TA epithelial cells and MRC-5 fibroblasts, and their relationship with CYP 2E1 and GSTT1 activity. High concentrations of these HMs induced cytotoxicity, particularly in cells treated with BrCHCl(2). Low concentrations of BrCHCl(2) stimulated hyperproliferation of fibroblasts, the most probable consequence of which is regenerative proliferation related to collagen induction. Fibroblasts exposed to BrCHCl(2) exhibited low levels of CYP 2E1 activity suggesting that released bromine is able to alter this activity by affecting the active site or auto regulating the activity itself. GSTT1 was up to ten times more active than CYP 2E1 in both cell lines, indicating that potential lung damage is due to formation of pro-carcinogens such as formaldehyde.

  3. Early experience with "antigenoid" vaccine Ac NFU1(S-) MRC towards prevention or modification of herpes genitalis.

    PubMed

    Skinner, G R; Woodman, C; Hartley, C; Buchan, A; Fuller, A; Wiblin, C; Wilkins, G; Melling, J

    1982-01-01

    The preparation and early clinical experience with "antigenoid" vaccine Ac NFU1(S-) MRC is described. A neutralising antibody response against both type 1 and type 2 herpes simplex virus was stimulated in 19 of 21 and 25 of 60 patients who received the high and low dosage of vaccine, respectively: immunoprecipitating antibody against type-common virus antigen "band II", a virus antigen of major importance in neutralization of herpes simplex virus, was detected in 12 of 19 and 2 of consorts who received the high and low dosage vaccine, respectively. To date, after a mean follow-up period of one year, none of the 42 consorts have contracted herpes genitalis: following a mean follow-up period of 6 months, only 1 patient vaccinated after the initial clinical episode has reported a recurrence of herpetic disease. These results compare favourably with the rates of consort transmission and first year recurrences in unvaccinated subjects. Seventeen of 24 patients with recurrent herpetic disease reported an "improvement" in terms of modification of the frequency, severity or extent of herpetic lesions. There were no important side-effects from vaccination: most patients experienced a degree of minor local reaction at the vaccination site for 24-72 hours and 3 patients reported a mild transient "flu-like" syndrome which disappeared within 48 hours of vaccination. It is intended to subject these data to the scrutiny of a placebo-controlled trial with an objective system of clinical assessment.

  4. The preparation, efficacy and safety of 'antigenoid' vaccine NFU1 (S-L+) MRC toward prevention of herpes simplex virus infections in human subjects.

    PubMed

    Skinner, G R; Buchan, A; Hartley, C E; Turner, S P; Williams, D R

    1980-01-01

    Vaccine NFU1 (S-L+) MRC was prepared by high multiplicity infection of serum-deprived human embryonic lung (MRC 5) cells with type 1 Herpes simplex virus. The preparative process removed inoculum virus particles and virus DNA while virus particle and DNA synthesis was inhibited by the presence of lithium chloride in the cell culture medium. The vaccine stimulated neutralising antibody in vaccinated mice and provided long-term protection against intra-vaginal challenge with type 2 herpes virus. The safety of the vaccine was confirmed by inoculation into newborn mice and cell lines of human, mammalian, and rodent origin. There was no evidence of cell transformation in vitro or of oncogenicity or teratogenicity in rodent species. It is intended to investigate the efficiency of this vaccine in human subjects.

  5. Dengue Type Four Viruses with E-Glu345Lys Adaptive Mutation from MRC-5 Cells Induce Low Viremia but Elicit Potent Neutralizing Antibodies in Rhesus Monkeys

    PubMed Central

    Li, Xiao-Feng; Tsai, Meng-Ju; Hsiao, Hung-Ju; Peng, Jia-Guan; Sue, Shih-Che; Qin, Cheng-Feng; Wu, Suh-Chin

    2014-01-01

    Knowledge of virulence and immunogenicity is important for development of live-attenuated dengue vaccines. We previously reported that an infectious clone-derived dengue type 4 virus (DENV-4) passaged in MRC-5 cells acquired a Glu345Lys (E-E345K) substitution in the E protein domain III (E-DIII). The same cloned DENV-4 was found to yield a single E-Glu327Gly (E-E327G) mutation after passage in FRhL cells and cause the loss of immunogenicity in rhesus monkeys. Here, we used site-directed mutagenesis to generate the E-E345K and E-E327G mutants from DENV-4 and DENV-4Δ30 infectious clones and propagated in Vero or MRC-5 cells. The E-E345K mutations were consistently presented in viruses recovered from MRC-5 cells, but not Vero cells. Recombinant E-DIII proteins of E345K and E327G increased heparin binding correlated with the reduced infectivity by heparin treatment in cell cultures. Different from the E-E327G mutant viruses to lose the immunogencity in rhesus monkeys, the E-E345K mutant viruses were able to induce neutralizing antibodies in rhesus monkeys with an almost a 10-fold lower level of viremia as compared to the wild type virus. Monkeys immunized with the E-E345K mutant virus were completely protected with no detectable viremia after live virus challenges with the wild type DENV-4. These results suggest that the E-E345K mutant virus propagated in MRC-5 cells may have potential for the use in live-attenuated DENV vaccine development. PMID:24959738

  6. Dengue type four viruses with E-Glu345Lys adaptive mutation from MRC-5 cells induce low viremia but elicit potent neutralizing antibodies in rhesus monkeys.

    PubMed

    Lin, Hsiao-Han; Lee, Hsiang-Chi; Li, Xiao-Feng; Tsai, Meng-Ju; Hsiao, Hung-Ju; Peng, Jia-Guan; Sue, Shih-Che; Qin, Cheng-Feng; Wu, Suh-Chin

    2014-01-01

    Knowledge of virulence and immunogenicity is important for development of live-attenuated dengue vaccines. We previously reported that an infectious clone-derived dengue type 4 virus (DENV-4) passaged in MRC-5 cells acquired a Glu345Lys (E-E345K) substitution in the E protein domain III (E-DIII). The same cloned DENV-4 was found to yield a single E-Glu327Gly (E-E327G) mutation after passage in FRhL cells and cause the loss of immunogenicity in rhesus monkeys. Here, we used site-directed mutagenesis to generate the E-E345K and E-E327G mutants from DENV-4 and DENV-4Δ30 infectious clones and propagated in Vero or MRC-5 cells. The E-E345K mutations were consistently presented in viruses recovered from MRC-5 cells, but not Vero cells. Recombinant E-DIII proteins of E345K and E327G increased heparin binding correlated with the reduced infectivity by heparin treatment in cell cultures. Different from the E-E327G mutant viruses to lose the immunogencity in rhesus monkeys, the E-E345K mutant viruses were able to induce neutralizing antibodies in rhesus monkeys with an almost a 10-fold lower level of viremia as compared to the wild type virus. Monkeys immunized with the E-E345K mutant virus were completely protected with no detectable viremia after live virus challenges with the wild type DENV-4. These results suggest that the E-E345K mutant virus propagated in MRC-5 cells may have potential for the use in live-attenuated DENV vaccine development.

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

    NASA Astrophysics Data System (ADS)

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

    2009-09-01

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

  8. Extreme Gas Kinematics in the z=2.2 Powerful Radio Galaxy MRC 1138-262: Evidence for Efficient Active Galactic Nucleus Feedback in the Early Universe?

    NASA Astrophysics Data System (ADS)

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

    2006-10-01

    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 feedback in the optical emission line gas around the z=2.16 powerful radio galaxy MRC 1138-262, likely a massive galaxy in formation. The kiloparsec-scale kinematics, with FWHMs and relative velocities <~2400 km s-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 a few ×1060 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 cosmological significance that is similar to, or perhaps larger than, starburst-driven winds if MRC 1138-262 is indeed archetypal. Moreover, the outflow has the potential to remove significant gas fractions (<~50%) from a >L* galaxy within a few tens to 100 Myr, fast enough to preserve the observed [α/Fe] overabundance in massive galaxies at low redshift. Using simple arguments, it appears that feedback like that observed in MRC 1138-262 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. Based on observations collected at the European Southern Observatory, Very Large Telescope Array, Cerro Paranal; program Nos. 70.B-0545, 70.A-0229, and 076.A-0684.

  9. 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.

  10. 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.

  11. Efficacy of vaccine Ac NFU1 (S-) MRC 5 given after an initial clinical episode in the prevention of herpes genitalis.

    PubMed

    Woodman, C B; Buchan, A; Fuller, A; Hartley, C; Skinner, G R; Stocker, D; Sugrue, D; Clay, J C; Wilkins, G; Wiblin, C

    1983-10-01

    A subunit antigenoid vaccine, Ac NFU1 (S-) MRC 5, was used in patients who had had a clinical episode of herpes genitalis. The rate of recurrence was compared with that in unvaccinated patients to determine the efficacy of vaccination in preventing recurrence and spread of the virus in the community. Seven of 22 (31%) vaccinated patients had eight recurrences after the initial clinical episode; in contrast there were 51 recurrences in 17 of 20 (85%) unvaccinated patients. Although further studies are needed, the results indicate that the vaccine may prevent recurrent episodes of herpes genitalis and thereby reduce the dissemination of this virus in the population.

  12. Immunogenicity and Protective Efficacy in a Rhesus Monkey Model of Vaccine Ac NFU1(S-) MRC Against Primary Type 2 Herpes Simplex Virus Infection

    PubMed Central

    Skinner, G. R. B.; Buchan, A.; Williams, D.; Marsden, J.; Hartley, C.; Wilbanks, G.; Turyk, M.; Namkoong, E. S.

    1982-01-01

    Adult and juvenile Rhesus monkeys were vaccinated with sub-unit formaldehyde-inactivated vaccine Ac NFU1(S-) MRC; no local or systemic side-effects followed vaccination. Vaccinated monkeys developed neutralizing and immunoprecipitating antibody to both type 1 and 2 herpes simplex virus. Antibody levels declined with time but were re-stimulated after virus challenge and to a lesser extent after attempted virus reactivation. There was evidence of protection against s.c. challenge with live type 2 herpes simplex virus. PMID:6295430

  13. Efficacy of vaccine Ac NFU1 (S-) MRC 5 given after an initial clinical episode in the prevention of herpes genitalis.

    PubMed Central

    Woodman, C B; Buchan, A; Fuller, A; Hartley, C; Skinner, G R; Stocker, D; Sugrue, D; Clay, J C; Wilkins, G; Wiblin, C

    1983-01-01

    A subunit antigenoid vaccine, Ac NFU1 (S-) MRC 5, was used in patients who had had a clinical episode of herpes genitalis. The rate of recurrence was compared with that in unvaccinated patients to determine the efficacy of vaccination in preventing recurrence and spread of the virus in the community. Seven of 22 (31%) vaccinated patients had eight recurrences after the initial clinical episode; in contrast there were 51 recurrences in 17 of 20 (85%) unvaccinated patients. Although further studies are needed, the results indicate that the vaccine may prevent recurrent episodes of herpes genitalis and thereby reduce the dissemination of this virus in the population. PMID:6311322

  14. Low concentration of PDGF-AB shows synergism with IFN-α in induction of IFN-β and -γ in MRC5 fibroblasts.

    PubMed

    Šantak, G; Šantak, M; Forčić, D

    2013-11-01

    Platelet-derived growth factor (PDGF) is a potent mediator of fibroblast proliferation and chemotaxis. Also it has been reported as a strong suppressor of interferon (IFN) expression. IFN-α has opposite effect on fibroblast function and IFN induction. Here is our early report on the effect of low concentration of PDGF-AB alone or in combination with IFN-α on IFN mRNA production in MRC5 fibroblasts. MRC5 cells incubated with IFN-α or PDGF-AB, alone or in combination, produced significant induction of IFN-α, -β and -γ mRNA in comparison with untreated cells. The induction was dose-dependent, with higher effect in cells treated with lower concentrations of PDGF-AB. Also, low concentration of PDGF-AB showed synergism with IFN-α in IFN-β and -γ induction. Results presented here open new possibilities in multi-cytokine therapy and expand previous results on PDGF activity.

  15. 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.

  16. 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

    2016-01-14

    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.

  17. 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

  18. The MRC National Survey of Health and Development reaches age 70: maintaining participation at older ages in a birth cohort study.

    PubMed

    Kuh, Diana; Wong, Andrew; Shah, Imran; Moore, Adam; Popham, Maria; Curran, Philip; Davis, Daniel; Sharma, Nikhil; Richards, Marcus; Stafford, Mai; Hardy, Rebecca; Cooper, Rachel

    2016-11-01

    A life course approach to ageing relies on maintaining participation rates in national birth cohorts and other long-term longitudinal studies. This reduces the risk of selective attrition biasing associations between lifetime risk factors and health outcomes in later life and ensures the studies remain as representative as possible of the original population. We report the participation patterns for a postal questionnaire and home visit at 68-69 years of study members in the MRC National Survey of Health and Development, the oldest and longest-running British birth cohort study. We investigated how participation varied by lifetime and recent contact, health status, previous clinical feedback and study engagement, taking account of prior socioeconomic and cognitive characteristics. Overall participation and home visit participation remained high (94 and 80%, respectively) and there were no gender differences. Participation was higher in those with higher levels of prior contact and lower in those with the poorest health status. Having previously received clinical feedback on actionable blood results was associated with reduced home visit participation but other forms of clinical feedback were not associated with subsequent participation. Activities that fostered study engagement were associated with increased home visit participation. These findings inform strategies to maintain participation in life course studies.

  19. Resistance Prediction in AML: Analysis of 4,601 Patients from MRC/NCRI, HOVON/SAKK, SWOG, and MD Anderson Cancer Center

    PubMed Central

    Walter, Roland B.; Othus, Megan; Burnett, Alan K.; Löwenberg, Bob; Kantarjian, Hagop M.; Ossenkoppele, Gert J.; Hills, Robert K.; Ravandi, Farhad; Pabst, Thomas; Evans, Anna; Pierce, Sherry R.; Vekemans, Marie-Christiane; Appelbaum, Frederick R.; Estey, Elihu H.

    2014-01-01

    Therapeutic resistance remains the principal problem in acute myeloid leukemia (AML). We used area under receiver operator characteristic curves (AUC) to quantify our ability to predict therapeutic resistance in individual patients where AUC=1.0 denotes perfect prediction and AUC=0.5 denotes a coin flip, using data from 4,601 patients with newly diagnosed AML given induction therapy with 3+7 or more intense standard regimens in MRC/NCRI, HOVON, SWOG, and MD Anderson Cancer Center studies. Age, performance status, white blood cell count, secondary disease, cytogenetic risk, and FLT3-ITD/NPM1 mutation status were each independently associated with failure to achieve complete remission despite no early death (“primary refractoriness”). However, the AUC of a bootstrap-corrected multivariable model predicting this outcome was only 0.78, indicating only fair predictive ability. Removal of FLT3-ITD and NPM1 information only slightly decreased the AUC (0.76). Prediction of resistance, defined as primary refractoriness or short relapse-free survival (RFS), was even more difficult. Our ability to forecast resistance based on routinely available pre-treatment covariates provides a rationale for continued randomization between standard and new therapies and supports further examination of genetic and post-treatment data to optimize resistance prediction in AML. PMID:25113226

  20. 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

  1. Rmi1 functions in S phase-mediated cohesion establishment via a pathway involving the Ctf18-RFC complex and Mrc1.

    PubMed

    Lai, Mong Sing; Seki, Masayuki; Tada, Shusuke; Enomoto, Takemi

    2012-10-26

    Saccharomyces cerevisiae RecQ helicase (Sgs1) combines with DNA topoisomerase III (Top3) and RecQ-mediated genome instability 1 (Rmi1) to form an evolutionarily conserved complex that is required for processing homologous recombination intermediates and restarting collapsed replication forks. It was previously reported that Rmi1 contributes to sister chromatid cohesion; however, the underlying molecular mechanism has been unclear. In the present study, Rmi1 was found to be enriched at the region close to an early-firing replication origin when replication forks were arrested near their origins in the presence of hydroxyurea. Genetic analyses revealed that Rmi1 promoted sister chromatid cohesion in a process that was distinct from both the cohesion establishment pathway involving Ctf4, Csm3, and Chl1 and the pathway involving the acetylation of Smc3. On the other hand, Rmi1 seemed to function in a pathway involving the Ctf18-RFC complex and Mrc1, which were previously predicted to regulate leading-strand DNA replication.

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

    NASA Astrophysics Data System (ADS)

    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.

  3. Genetic instability is prevented by Mrc1-dependent spatio-temporal separation of replicative and repair activities of homologous recombination: homologous recombination tolerates replicative stress by Mrc1-regulated replication and repair activities operating at S and G2 in distinct subnuclear compartments.

    PubMed

    Prado, Félix

    2014-05-01

    Homologous recombination (HR) is required to protect and restart stressed replication forks. Paradoxically, the Mrc1 branch of the S phase checkpoints, which is activated by replicative stress, prevents HR repair at breaks and arrested forks. Indeed, the mechanisms underlying HR can threaten genome integrity if not properly regulated. Thus, understanding how cells avoid genetic instability associated with replicative stress, a hallmark of cancer, is still a challenge. Here I discuss recent results that support a model by which HR responds to replication stress through replicative and repair activities that operate at different stages of the cell cycle (S and G2, respectively) and in distinct subnuclear structures. Remarkably, the replication checkpoint appears to control this scenario by inhibiting the assembly of HR repair centers at stressed forks during S phase, thereby avoiding genetic instability.

  4. Biopsy proportion of tumour predicts pathological tumour response and benefit from chemotherapy in resectable oesophageal carcinoma: results from the UK MRC OE02 trial

    PubMed Central

    Hale, Matthew D.; Nankivell, Matthew; Hutchins, Gordon G.; Stenning, Sally P.; Langley, Ruth E.; Mueller, Wolfram; West, Nicholas P.; Wright, Alexander I.; Treanor, Darren; Hewitt, Lindsay C.; Allum, William H.; Cunningham, David; Hayden, Jeremy D.; Grabsch, Heike I.

    2016-01-01

    Background Neoadjuvant chemotherapy followed by surgery is the standard of care for UK patients with locally advanced resectable oesophageal carcinoma (OeC). However, not all patients benefit from multimodal treatment and there is a clinical need for biomarkers which can identify chemotherapy responders. This study investigated whether the proportion of tumour cells per tumour area (PoT) measured in the pre-treatment biopsy predicts chemotherapy benefit for OeC patients. Patients and methods PoT was quantified using digitized haematoxylin/eosin stained pre-treatment biopsy slides from 281 OeC patients from the UK MRC OE02 trial (141 treated by surgery alone (S); 140 treated by 5-fluorouracil/cisplatin followed by surgery (CS)). The relationship between PoT and clinicopathological data including tumour regression grade (TRG), overall survival and treatment interaction was investigated. Results PoT was associated with chemotherapy benefit in a non-linear fashion (test for interaction, P=0.006). Only patients with a biopsy PoT between 40% and 70% received a significant survival benefit from neoadjuvant chemotherapy (N=129; HR (95%CI):1.94 (1.39-2.71), unlike those with lower or higher PoT (PoT<40%, N=39, HR:1.25 (0.66-2.35); PoT>70% (N=28, HR:0.65 (0.36-1.18)). High pre-treatment PoT was related to lack of primary tumour regression (TRG 4 or 5), P=0.0402. Conclusions This is the first study to identify in a representative subgroup of OeC patients from a large randomized phase III trial that the proportion of tumour in the pre-chemotherapy biopsy predicts benefit from chemotherapy and may be a clinically useful biomarker for patient treatment stratification. PMID:27769054

  5. The role of CSM3, MRC1, and TOF1 in minisatellite stability and large loop DNA repair during meiosis in yeast.

    PubMed

    LeClere, Andrea R; Yang, John K; Kirkpatrick, David T

    2013-01-01

    Double-stranded break (DSB) repair during meiotic recombination in yeast Saccharomyces cerevisiae leads to the formation of heteroduplex DNA, a hybrid DNA molecule composed of single strands from two homologous chromosomes. Differences in sequence between the strands within heteroduplex DNA generate mismatches or large unpaired loops that are substrates for repair. At least two pathways function to repair large loops that form within heteroduplex DNA: the RAD1-dependent large loop repair (LLR) pathway and another as yet uncharacterized RAD1-independent LLR pathway. Repair of large loops during meiotic recombination is especially important for the genomic stability of the repetitive DNA sequences known as minisatellites. Minisatellite DNA tracts are generally stable during mitotic cell divisions but frequently alter in length during meiosis. Using a yeast minisatellite system in which the human minisatellite associated with the HRAS1 proto-oncogene has been inserted into the recombination hotspot region upstream of HIS4 in S. cerevisiae, our lab previously showed that the RAD1-dependent LLR pathway controls minisatellite length expansions, but not contractions. Here we show that minisatellite length expansions are controlled by the products of the CSM3 and TOF1 genes, while contractions are controlled by MRC1. By examining meiotic segregation patterns in yeast strains heterozygous for the 26bp his4-lopd insert, we found that deleting CSM3 caused a loss of LLR activity similar to that seen in a RAD1 mutant. Double mutant analysis revealed that failure to repair loops is exacerbated upon deleting both RAD1 and CSM3 - specifically the type of repair that fills in loops, which would generate minisatellite length expansions. A model for minisatellite length alteration based on these results is presented.

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

    PubMed

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

    1996-07-01

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

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

    PubMed

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

    2015-08-03

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

  8. The "Methyl-CpG Binding Domain protein 2" plays a repressive role in relation to the promoter CpG content in the normal human cell line MRC5.

    PubMed

    Perriaud, Laury; Lachuer, Joel; Dante, Robert

    2014-01-01

    In cancer cells, methylation-dependent gene silencing is at least partly mediated by the "Methyl-CpG-Binding Domain protein 2" (MBD2 protein), via the recruitment of chromatin remodeling complexes. However this repressive role was poorly investigated in normal cells. To identify the genes repressed by MBD2 in these cells, we have determined the impact of MBD2 depletion on gene expression in human embryonic MRC5 fibroblasts, using RNA inference combined with microarray analysis. The up-regulation of some randomly selected genes was confirmed and a direct association between gene repression and MBD2 binding on methylated promoters associated to these genes was subsequently established. This control of gene expression appears to depend on the CpG content of promoters as MBD2 depletion was not sufficient to induce the expression of silent genes associated with High-CpG promoters, but it was required to achieve the methyl-dependent transcriptional locking of the genes associated with promoters exhibiting intermediate CpG content. Therefore, MBD2 seems to play a selective role in gene repression depending on the CpG content of the promoter regions.

  9. Fludarabine and cytosine are less effective than standard ADE chemotherapy in high-risk acute myeloid leukemia, and addition of G-CSF and ATRA are not beneficial: results of the MRC AML-HR randomized trial.

    PubMed

    Milligan, Donald W; Wheatley, Keith; Littlewood, Timothy; Craig, Jenny I O; Burnett, Alan K

    2006-06-15

    The optimum chemotherapy schedule for reinduction of patients with high-risk acute myeloid leukemia (relapsed, resistant/refractory, or adverse genetic disease) is uncertain. The MRC AML (Medical Research Council Acute Myeloid Leukemia) Working Group designed a trial comparing fludarabine and high-dose cytosine (FLA) with standard chemotherapy comprising cytosine arabinoside, daunorubicin, and etoposide (ADE). Patients were also randomly assigned to receive filgrastim (G-CSF) from day 0 until neutrophil count was greater than 0.5 x 10(9)/L (or for a maximum of 28 days) and all-trans retinoic acid (ATRA) for 90 days. Between 1998 and 2003, 405 patients were entered: 250 were randomly assigned between FLA and ADE; 356 to G-CSF versus no G-CSF; 362 to ATRA versus no ATRA. The complete remission rate was 61% with 4-year disease-free survival of 29%. There were no significant differences in the CR rate, deaths in CR, relapse rate, or DFS between ADE and FLA, although survival at 4 years was worse with FLA (16% versus 27%, P = .05). Neither the addition of ATRA nor G-CSF demonstrated any differences in the CR rate, relapse rate, DFS, or overall survival between the groups. In conclusion these findings indicate that FLA may be inferior to standard chemotherapy in high-risk AML and that the outcome is not improved with the addition of either G-CSF or ATRA.

  10. 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

  11. Costs of formal care for frail older people in England: the resource implications study of the MRC cognitive function and ageing study (RIS MRC CFAS).

    PubMed

    McNamee, P; Gregson, B A; Buck, D; Bamford, C H; Bond, J; Wright, K

    1999-02-01

    The aim of this paper is to quantify service use and costs of supporting frail older people at home in the community, using data collected in a longitudinal multicentre stratified randomised study for 1055 mentally frail, physically frail, and mentally and physically frail subjects. Average costs per person per week were found to total 64.45 Pounds Sterling, with a small number of services accounting for a large proportion of the total costs. The level of services offered by the nonstatutory voluntary and private sectors was found to be small. To highlight issues for policy makers, the extent of cost variations between a number of different subgroups were calculated. These bivariate analyses revealed substantial variation in costs, especially according to household structure, type of frailty, whether admission to continuing care accommodation occurred and survival. Multiple regression analysis demonstrated that 26% of the variation in log average weekly costs could be explained by a number of socio-demographic and health status variables. A particularly close relationship was observed between costs and whether admission to continuing care accommodation occurred, highlighting a need for policy-makers to examine the nature and scale of provision of alternative community based care packages. The results demonstrate that descriptive cost data such as those presented can provide information useful to the planning process, enabling more informed choices to be made over the provision of services for particular groups of people.

  12. Be skeptical about unexpected large apparent treatment effects: the case of an MRC AML12 randomization.

    PubMed

    Wheatley, Keith; Clayton, David

    2003-02-01

    The preliminary results of the twelfth Medical Research Council acute myeloid leukemia trial show no evidence of a survival advantage for five courses of therapy compared to four courses in a randomized comparison involving 1078 patients (hazard ratio 1.09, 95% confidence interval [CI] 0.87-1.37, p=0.4). However, the data presented to the independent data monitoring and ethics committee (DMEC) at both its reviews in 1998 suggested large benefits for the additional course with hazard ratios of 0.47 and 0.55 (95% CIs 0.29-0.77 and 0.38-0.80, p=0.003 and p=0.002, respectively). Despite these highly significant findings, the DMEC did not recommend closure of the randomization, a decision vindicated by the subsequent reversion to a null result. The main reason for not closing the randomization was that the treatment effects observed in 1998 (53% and 45% reductions in the odds of death) were considered too large to be clinically plausible, despite the p-values associated with them. Investigations have not identified any clinical explanations, such as different types of patients in the early and later parts of the trial, to explain the loss of benefit as the trial progressed. Thus, the most likely current explanation for the large benefit observed early on is the play of chance. Lessons to be learned from this example are that: fixed stopping rules based on some predetermined p-value should not be used and the decision to close a randomization or not should take account of other factors such as the medical plausibility of the magnitude of the treatment effect; chance effects do occur and happen more frequently than many clinicians realize; it is important that DMEC members are experienced in the interpretation of clinical trial evidence and aware of the dangers of early stopping without wholly convincing evidence.

  13. MRC trial of treatment of mild hypertension: principal results. Medical Research Council Working Party.

    PubMed Central

    1985-01-01

    The main aim of the trial was to determine whether drug treatment of mild hypertension (phase V diastolic pressure 90-109 mm Hg) reduced the rates of stroke, of death due to hypertension, and of coronary events in men and women aged 35-64 years. Subsidiary aims were: to compare the course of blood pressure in two groups, one taking bendrofluazide and one taking propranolol, and to compare the incidence of suspected adverse reactions to these two drugs. The study was single blind and based almost entirely in general practices; 17 354 patients were recruited, and 85 572 patient years of observation have accrued. Patients were randomly allocated at entry to take bendrofluazide or propranolol or placebo tablets. The primary results were as follows. The stroke rate was reduced on active treatment: 60 strokes occurred in the treated group and 109 in the placebo group, giving rates of 1.4 and 2.6 per 1000 patient years of observation respectively (p less than 0.01 on sequential analysis). Treatment made no difference, however, to the overall rates of coronary events: 222 events occurred on active treatment and 234 in the placebo group (5.2 and 5.5 per 1000 patient years respectively). The incidence of all cardiovascular events was reduced on active treatment: 286 events occurred in the treated group and 352 in the placebo group, giving rates of 6.7 and 8.2 per 1000 patient years respectively (p less than 0.05 on sequential analysis). For mortality from all causes treatment made no difference to the rates. There were 248 deaths in the treated group and 253 in the placebo group (rates 5.8 and 5.9 per 1000 patient years respectively). Several post hoc analyses of subgroup results were also performed but they require very cautious interpretation. The all cause mortality was reduced in men on active treatment (157 deaths versus 181 in the placebo group; 7.1 and 8.2 per 1000 patient years respectively) but increased in women on active treatment (91 deaths versus 72; 4.4 and 3.5 per 1000 patient years respectively). The difference between the sexes in their response to treatment was significant (p = 0.05). Comparison of the two active drugs showed that the reduction in stroke rate on bendrofluazide was greater than that on propranolol (p = 0.002). The stroke rate was reduced in both smokers and non-smokers taking bendrofluazide but only in non-smokers taking propranolol. This difference between the responses to the two drugs was significant (p = 0.03).(ABSTRACT TRUNCATED AT 400 WORDS) PMID:2861880

  14. Modular Research-Based Composably Trustworthy Mission-Oriented Resilient Clouds (MRC2)

    DTIC Science & Technology

    2016-02-01

    efficiency , and resilience. We built on the foundations of a companion DARPA project, CRASH-worthy Trustworthy Systems Research and Development (CTSRD...beneficial tradeoffs between security and energy efficiency • Advancing multi-scale computing techniques • Exploiting capability- system security...overall energy efficiency are total system -network emergent properties that must be defined hierarchically, because they have potentially different

  15. 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

  16. 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

  17. 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

  18. 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.

  19. 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…

  20. Issues in applying multi-arm multi-stage methodology to a clinical trial in prostate cancer: the MRC STAMPEDE trial

    PubMed Central

    Sydes, Matthew R; Parmar, Mahesh KB; James, Nicholas D; Clarke, Noel W; Dearnaley, David P; Mason, Malcolm D; Morgan, Rachel C; Sanders, Karen; Royston, Patrick

    2009-01-01

    Background The multi-arm multi-stage (MAMS) trial is a new paradigm for conducting randomised controlled trials that allows the simultaneous assessment of a number of research treatments against a single control arm. MAMS trials provide earlier answers and are potentially more cost-effective than a series of traditionally designed trials. Prostate cancer is the most common tumour in men and there is a need to improve outcomes for men with hormone-sensitive, advanced disease as quickly as possible. The MAMS design will potentially facilitate evaluation and testing of new therapies in this and other diseases. Methods STAMPEDE is an open-label, 5-stage, 6-arm randomised controlled trial using MAMS methodology for men with prostate cancer. It is the first trial of this design to use multiple arms and stages synchronously. Results The practical and statistical issues faced by STAMPEDE in implementing MAMS methodology are discussed and contrasted with those for traditional trials. These issues include the choice of intermediate and final outcome measures, sample size calculations and the impact of varying the assumptions, the process for moving between trial stages, stopping accrual to each trial arm and overall, and issues around perceived trial complexity. Conclusion It is possible to use the MAMS design to initiate and undertake large scale cancer trials. The results from STAMPEDE will not be known for some years but the lessons learned from running a MAMS trial are shared in the hope that other researchers will use this exciting and efficient method to perform further randomised controlled trials. Trial registration ISRCTN78818544, NCT00268476 PMID:19519885

  1. 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.

  2. Comparison of 1 + 5 DAT and 3 + 10 DAT followed by COAP or MAZE consolidation therapy in the treatment of acute myeloid leukemia: MRC ninth AML trial.

    PubMed

    Rees, J K; Gray, R

    1987-06-01

    This trial, which will probably accrue over 1,000 patients before it closes, has already demonstrated that high remission rates are attainable in large multicenter studies using 'conventional' doses of ara-C. The results in the group aged less than 40 are comparable with many single-center studies. There is, at the moment, only a borderline difference in the remission rates between the two forms of induction therapy but the more intensive regimen of DAT 3 + 10 achieves remission more quickly and requires less supportive care. Analysis of the reasons for failure to enter remission continues to show that inadequate supportive care remains an important reason why the remission rates are not higher. Drug-related deaths in remission, though decreasing gradually in this study, are a disturbing consequence of increasing the intensity of consolidation treatment.

  3. 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.

  4. 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

  5. Resistance prediction in AML: analysis of 4601 patients from MRC/NCRI, HOVON/SAKK, SWOG and MD Anderson Cancer Center.

    PubMed

    Walter, R B; Othus, M; Burnett, A K; Löwenberg, B; Kantarjian, H M; Ossenkoppele, G J; Hills, R K; Ravandi, F; Pabst, T; Evans, A; Pierce, S R; Vekemans, M-C; Appelbaum, F R; Estey, E H

    2015-02-01

    Therapeutic resistance remains the principal problem in acute myeloid leukemia (AML). We used area under receiver-operating characteristic curves (AUCs) to quantify our ability to predict therapeutic resistance in individual patients, where AUC=1.0 denotes perfect prediction and AUC=0.5 denotes a coin flip, using data from 4601 patients with newly diagnosed AML given induction therapy with 3+7 or more intense standard regimens in UK Medical Research Council/National Cancer Research Institute, Dutch-Belgian Cooperative Trial Group for Hematology/Oncology/Swiss Group for Clinical Cancer Research, US cooperative group SWOG and MD Anderson Cancer Center studies. Age, performance status, white blood cell count, secondary disease, cytogenetic risk and FLT3-ITD/NPM1 mutation status were each independently associated with failure to achieve complete remission despite no early death ('primary refractoriness'). However, the AUC of a bootstrap-corrected multivariable model predicting this outcome was only 0.78, indicating only fair predictive ability. Removal of FLT3-ITD and NPM1 information only slightly decreased the AUC (0.76). Prediction of resistance, defined as primary refractoriness or short relapse-free survival, was even more difficult. Our limited ability to forecast resistance based on routinely available pretreatment covariates provides a rationale for continued randomization between standard and new therapies and supports further examination of genetic and posttreatment data to optimize resistance prediction in AML.

  6. Child Behavior Research. A Survey of British Research Into Child Psychiatric Disorder and Normal Social Development. A Report to the MRC Child Psychiatry Sub-Committee.

    ERIC Educational Resources Information Center

    Shaffer, D., Comp.

    Approximately 250 abstracts of currently active (1975-1976) British research into child psychiatric disorder and normal social development are presented. It is explained that the information was gathered from a 1974 survey of research and education organizations, child psychiatrists at medical schools, and the heads of academic departments of…

  7. 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

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

    PubMed

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

    2008-09-15

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

  9. Interferon alfa-2a versus combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil in patients with untreated metastatic renal cell carcinoma (MRC RE04/EORTC GU 30012): an open-label randomised trial

    PubMed Central

    Gore, Martin E; Griffin, Clare L; Hancock, Barry; Patel, Poulam M; Pyle, Lynda; Aitchison, Michael; James, Nicholas; Oliver, Roderick TD; Mardiak, Jozef; Hussain, Tahera; Sylvester, Richard; Parmar, Mahesh KB; Royston, Patrick; Mulders, Peter FA

    2010-01-01

    Summary Background In metastatic renal cell carcinoma combinations of interferon alfa-2a, interleukin-2, and fluorouracil produce higher response rates and longer progression-free survival than do single agents. We aimed to compare overall survival in patients receiving combination treatment or interferon alfa-2a. Methods RE04/30012 was an open-label randomised trial undertaken in 50 centres across eight countries. 1006 treatment-naive patients diagnosed with advanced metastatic renal cell carcinoma were randomly allocated (1 to 1) by minimisation to receive interferon alfa-2a alone or combination therapy with interferon alfa-2a, interleukin-2, and fluorouracil. Treatment was not masked. The primary endpoint was overall survival. Treatment groups were compared with a non-stratified log-rank test. Analysis was by intention to treat. This study is registered, number ISRCTN 46518965. Findings 502 patients were randomly assigned to receive interferon alfa-2a and 504 to receive combined treatment. Median follow-up was 37·2 months (24·8–52·3). Median overall survival was 18·8 months (17·0–23·2) for patients receiving interferon alfa-2a versus 18·6 months (16·5–20·6) for those receiving combination therapy. Overall survival did not differ between the two groups (hazard ratio 1·05 [95% CI 0·90–1·21], p=0·55; absolute difference 0·3% (−5·1 to 5·6) at 1 year and 2·7% (−8·2 to 2·9) at 3 years). Serious adverse events were reported in 113 (23%) patients receiving interferon alfa-2a and 131 (26%) of those receiving combined treatment. Interpretation Although combination therapy does not improve overall or progression-free survival compared with interferon alfa-2a alone, immunotherapy might still have a role because it can produce remissions that are of clinically relevant length in some patients. Identification of patients who will benefit from immunotherapy is crucial. Funding UK Medical Research Council. PMID:20153039

  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. The efficiency of Gd-EOB-DTPA-enhanced magnetic resonance cholangiography in living donor liver transplantation: a preliminary study.

    PubMed

    Ogul, Hayri; Kantarci, Mecit; Pirimoglu, Berhan; Karaca, Leyla; Aydinli, Bulent; Okur, Aylin; Ozturk, Gurkan; Kizrak, Yesim

    2014-03-01

    The aim of this study was to evaluate utility of gadoxetic acid disodium (Gd-EOB-DTPA)-enhanced magnetic resonance cholangiography (MRC) for the detection of biliary complications after living donor liver transplantation (LDLT). A total of 18 patients with suspected biliary complications underwent MRC. T2-weighted MRC and contrast-enhanced MRC (CE-MRC) were used to identify the biliary complications. MRC included routine breath-hold T2-weighted MRC using half-Fourier acquisition single-shot turbo spin-echo (HASTE) sequences and Gd-EOB-DTPA-enhanced MRC T1-weighted volumetric interpolated breath-hold examination (VIBE) sequences. Before confirming the biliary complications, one observer reviewed the MRC images and the CE-MRC images separately. The verification procedures and MRC findings were compared, and the sensitivity, specificity, and accuracy of both techniques were calculated for the identification of biliary complications. The observer found six of seven biliary complications using CE-MRC. The sensitivity was 85.7% and the accuracy was 94.4%. Using MRC alone, sensitivity was 57.1% and accuracy was 55.5%. The accuracy of Gd-EOB-DTPA-enhanced MRC was superior to MRC in locating biliary leaks (p < 0.05). The usage of Gd-EOB-DTPA-enhanced MRC yields information that complements the MRC findings that improve the identification of biliary complications. We recommend the use of MRC in addition to Gd-EOB-DTPA-enhanced MRC to increase the preoperative accuracy when assessing the biliary complications after LDLT.

  12. 78 FR 59994 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-30

    ... OCC's By-Laws and Rules that set forth powers and duties of the MRC, which are in fact contained in a... decision-making process at the MRC, which should ultimately lead to decisions that assure the...

  13. Activation of rat T lymphocytes by anti-CD2 monoclonal antibodies

    PubMed Central

    1988-01-01

    Rat T cells and thymocytes were induced to proliferate by a pair of mAbs, MRC OX-54 and MRC OX-55, directed against rat CD2. Accessory cells were required but their role was not simply for crosslinking of the two mAbs, as neither MRC OX-54 nor MRC OX-55 alone, in the presence of a crosslinking second antibody, caused T cell mitogenesis. Nor could the phorbol ester PMA replace either antibody. The two mAbs recognized distinct epitopes on rat CD2; however, MRC OX-54 could partially block MRC OX-55 binding whereas the reverse situation was not seen. A further CD2 epitope was recognized by two mutually competitive mAbs, MRC OX-34 and MRC OX-53, which were not mitogenic. Neither MRC OX-34 nor MRC OX- 53 affected the binding of MRC OX-54 or MRC OX-55, yet they prevented the mitogenic effect induced by these mAbs. The presence of mAbs against CD4 and the IL-2-R also abrogated this mitogenesis, whereas an anti-CD5 mAb augmented the CD2-induced proliferation. PMID:3133442

  14. A Constructive Method for Computing Generalized Manley-Rowe Constants of Motion

    NASA Astrophysics Data System (ADS)

    Kartashova, Elena; Tec, Loredana

    2013-10-01

    The Manley--Rowe constants of motion (MRC) are conservation laws written out for a dynamical system describing the time evolution of the amplitudes in resonant triad. In this paper we extend the concept of MRC to resonance clusters of any form yielding generalized Manley--Rowe constants (gMRC) and give a constructive method how to compute them. We also give details of a \\emph{Mathematica} implementation of this method. While MRC provide integrability of the underlying dynamical system, gMRC generally do not but may be used for qualitative and numerical study of dynamical systems describing generic resonance clusters.

  15. Evolution of an expanded mannose receptor gene family.

    PubMed

    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.

  16. Beam and Plasma Physics Research

    DTIC Science & Technology

    1990-06-01

    relativistic klystron amplifiers, virtual cathode oscillators, magnetically insulated transmission lines, transvertrons and vircator phase/frequency...Computational Physics Studies III MRC/ABQ-R-1278 101 03-08 SPHC Manual MRC/ABQ-R-1237 103 03-09 Diagnostic White Paper Contributions MRC/ABQ-N-451 106 9 2.2...magnetically insulated transmission line (MITL). Computations were performed using the particle-in-cell code CCUBE, developed originally by Los

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

    NASA Astrophysics Data System (ADS)

    Krach, F.

    1984-08-01

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

  18. Development of Ab-initio Multibody Energy Expansions for the Design of Metallic Materials with Extremal Properties

    DTIC Science & Technology

    2010-10-31

    algebra software like MAGMA [32]. In this work, we follow the Monomial Symmetrization Approach (MSA) of [8] to construct the polynomials. To introduce...doi:10.1002/mrc.1242. URL http://onlinelibrary.wiley.com/doi/10.1002/mrc.1242/pdf [32] W. Bosma, J. J. Cannon, C. Playoust, The Magma Algebra System I

  19. 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.…

  20. 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 &...

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  2. The route of passive chloride movement across amphibian skin: localization and regulatory mechanisms.

    PubMed

    Nagel, Wolfram; Somieski, Petra; Katz, Uri

    2002-11-13

    Transepithelial Cl(-) conductance (G(Cl)) in amphibian skin can be activated in several species by serosa positive potentials. Mitochondria-rich cells (MRC) or tight junctions (TJ) between the epithelial cells are possible sites for this pathway. The properties and the techniques used to investigate this pathway are reviewed in the present paper. In situ techniques are preferable, since specific properties of the MRC are apparently not maintained in isolated cells. Volume measurements and electronprobe microanalysis of intracellular ions suggest the localization of voltage-activated G(Cl) to MRC. G(Cl) correlates poorly with the density of MRC. The vibrating voltage probe allows quantitative correlation of the local Cl(-) current through morphologically identified structures and the transepithelial Cl(-) current. Our analysis shows that 80% of the voltage-activated Cl(-) current is accounted for by current through MRC or their immediate vicinity. The activation patterns of this current and the inhibition by the alpha(1)-adrenergic agonist, epinephrine, conform to those of the transepithelial current. However, less than 20% of the MRC are active at a certain moment and the activity is spontaneously variable with time. The molecular nature of this pathway, physiological control mechanisms and their relation to the temporal activity of MRC remain to be studied.

  3. 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.

  4. Mental time travel ability and the Mental Reinstatement of Context for crime witnesses.

    PubMed

    Smith-Spark, James H; Bartimus, Joshua; Wilcock, Rachel

    2017-02-01

    Mental time travel ability marks how well the phenomenological aspects of events are mentally re-experienced during recall. The Cognitive Interview (CI) elicits eyewitness information. One of its techniques, Mental Reinstatement of Context (MRC), asks eyewitnesses to reinstate the incident's context mentally before recall. Fifty-six participants watched a simulated crime video. Self-report measures were then taken to estimate general mental time travel ability. Participants were questioned subsequently about the video. Eyewitness performance under MRC was compared with the CI's Report Everything (RE) technique, wherein eyewitnesses recall everything they can but with no invitation to mentally reinstate the context. There was no effect of interview condition on accuracy of recall; however, general mental time travel ability was positively associated with the amount of correct and incorrect information produced under MRC, but not RE, conditions. This is the first empirical demonstration that MRC instructions engage the mental time travel capacities they purport to.

  5. 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

  6. 78 FR 17763 - Housatonic Railroad Company, Inc., Maybrook Railroad Company, and Housatonic Transportation...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-03-22

    ... Surface Transportation Board Housatonic Railroad Company, Inc., Maybrook Railroad Company, and Housatonic Transportation Company--Intra-Corporate Family Transaction Exemption Housatonic Railroad Company, Inc. (HRRC), Maybrook Railroad Company (MRC), and Housatonic Transportation Company (HTC) (collectively,...

  7. Receive Diversity Combining Techniques for SC-FDMA-Based Cooperative Relays

    NASA Astrophysics Data System (ADS)

    Woo, Kyung-Soo; Kim, Yeong-Jun; Yoo, Hyun-Il; Kim, Jaekwon; Yun, Sangboh; Cho, Yong-Soo

    In this letter, two receive diversity combining techniques are proposed for cooperative relay systems based on single-carrier frequency division multiple access (SC-FDMA) when relay station (RS) transmits the received signals from multiple mobile stations (MSs) together using one large size discrete Fourier transform (DFT). A simplified-MRC (S-MRC) technique performs diversity combining in the time-domain by using the estimated channel weights and initial estimates obtained by the SC-FDMA signal detector. An interference rejection-MRC (IR-MRC) technique performs diversity combining in the frequency-domain by adjusting the DFT spreading size at the receiver. It is shown by computer simulation that the proposed receive combining techniques achieve a significant diversity gain over the conventional techniques.

  8. 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.

  9. 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.

  10. Synthesis and cytotoxicity testing of new amido-substituted triazolopyrrolo[2,1-c][1,4]benzodiazepine (PBDT) derivatives.

    PubMed

    Sorra, Kumaraswamy; Chang, Chi-Fen; Pusuluri, Srinivas; Mukkanti, Khagga; Laiu, Min-Chiau; Bao, Bo-Ying; Su, Chia-Hao; Chuang, Ta-Hsien

    2012-07-25

    A series of amido-substituted triazolopyrrolo[2,1-c][1,4]benzodiazepine (PBDT) derivatives was synthesized from isatoic anhydride, and their cytotoxicity against the MRC-5 and Mahlavu cell lines was evaluated. The results suggest that compound PBDT-7i with the meta-trifluoromethylbenzoyl substituent can selectively inhibit the growth of Mahlavu cells and has low toxicity towards MRC-5 cells.

  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. 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.

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

    PubMed Central

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

    2016-01-01

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

  14. Gallbladder opacification on gadoxetate disodium-enhanced CT scan.

    PubMed

    Karam, Adib R; Scortegagna, Eduardo; Chen, Byron Y; Dupuis, Carolyn S; Coughlin, Dennis D

    2017-04-01

    This study aimed to evaluate the radiologist's ability to identify excreted gadoxetate disodium within the gallbladder on CT scan. Thirty three healthy adults underwent imaging of the liver during work-up for potential liver donation. Three patients had undergone prior cholecystectomy and therefore were excluded. Imaging consisted of gadoxetate disodium-enhanced magnetic resonance cholangiography (MRC) and multiphase contrast-enhanced CT scan of the abdomen and pelvis. Two fellowship-trained abdominal imaging radiologists, who were blinded to the MRC images and the contrast agent used during MRC, independently reviewed the CT scans of the 30 patients that were included. The scans were evaluated for the presence or absence of abnormal hyperdensity within the gallbladder. Three patients did not receive intravenous gadoxetate disodium, 4 patients had their MRC after the CT scan, and 1 patient had the CT scans 5 days following the MRC. Twenty two patients had the CT scan within 24 h following the gadoxetate disodium-enhanced MRC. Of the 22 patients expected to have gadolinium in the gallbladder, both reviewers identified hyperdensity in the same 20 patients (90%). Both reviewers reported no abnormal hyperdensity within the gallbladder in the remaining 10 patients. CT scan can reveal excreted gadoxetate disodium within the gallbladder lumen and therefore gadoxetate disodium-enhanced CT scan can potentially play a role in the evaluation of cystic duct patency and work-up of acute cholecystitis.

  15. 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

  16. 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

  17. 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

  18. Comparing the level of bystander effect in a couple of tumor and normal cell lines.

    PubMed

    Soleymanifard, Shokouhozaman; Bahreyni, Mohammad T Toossi

    2012-04-01

    Radiation-induced bystander effect refers to radiation responses which occur in non-irradiated cells. The purpose of this study was to compare the level of bystander effect in a couple of tumor and normal cell lines (QU-DB and MRC5). To induce bystander effect, cells were irradiated with 0.5, 2, and 4 Gy of (60)Co gamma rays and their media were transferred to non-irradiated (bystander) cells of the same type. Cells containing micronuclei were counted in bystander subgroups, non-irradiated, and 0.5 Gy irradiated cells. Frequencies of cells containing micronuclei in QU-DB bystander subgroups were higher than in bystander subgroups of MRC5 cells (P < 0.001). The number of micronucleated cells counted in non-irradiated and 0.5 Gy irradiated QU-DB cells was also higher than the corresponding values for MRC5 cells (P < 0.001). Another difference between the two cell lines was that in QU-DB bystander cells, a dose-dependent increase in the number of micronucleated cells was observed as the dose increased, but at all doses the number of micronucleated cells in MRC5 bystander cells was constant. It is concluded that QU-DB cells are more susceptible than MRC5 cells to be affected by bystander effect, and in the two cell lines there is a positive correlation between DNA damages induced directly and those induced due to bystander effect.

  19. Coordinating research and practice: challenges testing messages to increase medical reserve corps participation in local health department activities.

    PubMed

    Klaiman, Tamar; Higdon, Melissa; Galarce, Ezequiel

    2013-04-01

    Local health departments (LHDs) increasingly depend on volunteers, often Medical Reserve Corps (MRC) volunteers, to assist with a variety of functions. While LHDs have extensive lists of volunteers, only about 10 % are actively involved in LHD activities. Psychological literature has shown that well-designed messages can motivate behavior among individuals. Key to this theory is the concept of "framing," defined as the influence the characterization of an issue can have on its understanding. Research has been conducted on how to frame and disseminate both political and public health messages to alter individual behavior. We aimed to design and test appropriate evidence-based messages to increase volunteer participation rates in LHD flu clinics. After inviting over 900 MRC units to participate during the 2011-2012 influenza season, five were able to collect and report data to the research team. Using a randomized trial design, we tested messages among the five participating MRC units consisting of a total of 2,020 volunteers. Chi Square analysis showed no difference in attendance between those who received either of the test messages versus the control message (p = .305). Our small sample size of MRC units likely biased our sample and reduced the external validity of our study. Our experience in conducting research with MRC coordinators and volunteers highlights the challenges of conducting research with practitioners who lack the time, infrastructure and resources necessary to work with researchers. There is a strong need for more supportive infrastructure for conducting research with practitioners.

  20. 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.

  1. Detection of human cytomegalovirus in clinical specimens by centrifugation culture with a nonhuman cell line.

    PubMed Central

    Gleaves, C A; Hursh, D A; Meyers, J D

    1992-01-01

    The sensitivities of MRC-5 and mink lung (ML) cells in centrifugation culture were compared simultaneously for the detection of cytomegalovirus (CMV) IE antigen (immediate-early antigen) from clinical specimens. Of 413 samples assayed, 51 (12%) were positive for CMV by both centrifugation and standard cell culture. At 20 h postinoculation (p.i.), 46 of 51 (90.2%) CMV-positive specimens were detected in ML cells. At 40 h p.i., 50 of 51 (98.0%) CMV-positive specimens were detected in ML cells, compared with 48 of 51 (94.0%) in MRC-5 cells. There was no significant difference in the detection of CMV in either cell line by centrifugation culture. However, in 19 of 23 positive samples that had countable foci at 20 h p.i., there was a 25% increase in the number of positive foci observed for ML cells compared with MRC-5 cells. Less toxicity was also noted for ML cells than for MRC cells, particularly in viral blood specimens. These data suggest that ML cells are comparable to MRC-5 cells for the rapid detection of CMV by centrifugation culture. PMID:1315330

  2. Forecasting the Marine Corps’ Enlisted Classification Plan: Assessment of An Alternative Model

    DTIC Science & Technology

    2012-03-01

    8217·"’ - rt01 ’·"’ ’"" ,..,. .... "" .... - rvO & ~. . 1.116 .... "’’ .... ,..., -+-N111 ,.., ~,,., Ull ..,. ,..., l,,ll - rvw ,.,, ""’ 1.914 1.$1$ 1

  3. Interobserver agreement in the assessment of muscle strength and functional abilities in Guillain-Barré syndrome.

    PubMed

    Kleyweg, R P; van der Meché, F G; Schmitz, P I

    1991-11-01

    In studies of Guillain-Barré syndrome, functional deficit is usually assessed according to a functional scale consisting of several categories. The level of interobserver agreement in this scoring method is not known; furthermore, this method seems to be insensitive when applied to bedridden and artificially ventilated patients. We have developed an additional score (MRC-sumscore), reflecting muscle strength in general. Both scoring methods, tested in Guillain-Barré patients, have an almost perfect interobserver agreement. For the functional score kappa = 0.85, and for the MRC-sumscore r2 = 0.96. The MRC-sumscore is easily assessed and more sensitive than the functional score when patients are bedridden or artificially ventilated.

  4. 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

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

    NASA Astrophysics Data System (ADS)

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

    2014-05-01

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

  6. Proposal for a New LoD and Multi-Representation Concept for CityGML

    NASA Astrophysics Data System (ADS)

    Löwner, M.-O.; Gröger, G.; Benner, J.; Biljecki, F.; Nagel, C.

    2016-10-01

    The Open Geospatial Consortium (OGC) CityGML standard offers a Level of Detail (LoD) concept that enables the representation of CityGML features from a very detailed to a less detailed description. Due to a rising application variety, the current LoD concept seems to be too inflexible. Here, we present a multi representation concept (MRC) that enables a user-defined definition of LoDs. Because CityGML is an international standard, official profiles of the MRC are proposed. However, encoding of the defined profiles reveals many problems including mapping the conceptual model to the normative encoding, missing technologies and so on. Therefore, we propose to use the MRC as a meta model for the further definition of an LoD concept for CityGML 3.0.

  7. Revised minimum reciprocity configuration and actualization methodology of interferometric all-fiber-optic gyroscopes.

    PubMed

    Wang, Xinyue; Wang, Ziyu

    2011-05-01

    We propose a revised minimum reciprocity configuration (MRC) of an interferometric all-fiber-optic gyroscope (all-fiber I-FOG), based on our design of a fused-taper polarization-maintaining fiber coupler. This MRC reduces the insertion loss and production cost of the optical path, yet maintains the principle of reciprocity. Experimental results show that this I-FOG with five optical components exhibits better performance than a conventional I-FOG with six optical components. Using the revised MRC, the angle random walk and the bias instability of an I-FOG are improved from 0.025 deg/√hr to 0.011 deg/√hr, and 0.48 deg/hr to 0.21 deg/hr, respectively.

  8. 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.

  9. 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.

  10. 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

  11. Structural analysis of mitochondrial mutations reveals a role for bigenomic protein interactions in human disease.

    PubMed

    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.

  12. Radiologic validation of a fast neutron multileaf collimator

    SciTech Connect

    Farr, J. B.; Maughan, R. L.; Yudelev, M.; Blosser, E.; Brandon, J.; Horste, T.; Forman, J. D.

    2007-09-15

    Teletherapy with high linear energy transfer radiations (LET), perhaps more than with low LET types, requires careful beam collimation to limit effects to normal structures. Intensity modulated techniques may also hold promise in this regard. Accordingly, a remote computer-controlled, high-resolution multileaf collimator (MLC) is placed into service at the Gershenson Radiation Oncology Center's fast neutron therapy center of the Karmanos Cancer Institute, Detroit, Michigan. Prior to clinical application the basic radiological properties of the fast neutron MLC are studied. Complicating the evaluation is the mixed neutron and gamma radiation field environment encountered with fast neutron beams. As a reference the MLC performance is compared to an existing multirod collimator (MRC) used at the facility for more than ten years. The MLC aggregate transmission is found to be about 4%, slightly outperforming the MRC. The measured gamma component for a closed collimator is 1.5 times higher for the MLC, compared with the MRC. The different materials used for attenuation, steel and tungsten, respectively account for the difference. The geometry for the MRC is double focused whereas that for the MLC is single focused. The resulting penumbrae agree between the focused axis of the MLC and both axes of the MRC. Penumbra differences between the focused and unfocused axes were not observable at small field sizes and a maximum of about 1 cm for a 25x25 cm{sup 2} field at 2.5 cm depth in water. For a 10x10 cm{sup 2} field the focused penumbra is 9 mm, and the unfocused is 12 mm. The many benefits of the fully automatic MLC over the semimanual MRC are considered to justify this compromise.

  13. Progress toward the development of a genetically engineered attenuated hepatitis A virus vaccine.

    PubMed Central

    Funkhouser, A W; Raychaudhuri, G; Purcell, R H; Govindarajan, S; Elkins, R; Emerson, S U

    1996-01-01

    Mutations which positively affect growth of hepatitis A virus in cell culture may negatively affect growth in vivo. Therefore, development of an attenuated vaccine for hepatitis A may require a careful balancing of mutations to produce a virus that will grow efficiently in cells suitable for vaccine production and still maintain a satisfactory level of attenuation in vivo. Since such a balance could be achieved most directly by genetic engineering, we are analyzing mutations that accumulated during serial passage of the HM-175 strain of hepatitis A virus in MRC-5 cell cultures in order to determine the relative importance of the mutations for growth in MRC-5 cells and for attenuation in susceptible primates. Chimeric viral genomes of the HM-175 strain were constructed from cDNA clones derived from a virulent virus and from two attenuated viruses adapted to growth in African green monkey kidney (AGMK) and MRC-5 cells, respectively. Viruses encoded by these chimeric genomes were recovered by in vitro or in vivo transfection and assessed for their ability to grow in cultured MRC-5 cells or to cause hepatitis in primates (tamarins). The only MRC-5-specific mutations that substantially increased the efficiency of growth in MRC-5 cells were a group of four mutations in the 5' noncoding (NC) region. These 5' NC mutations and a separate group of 5' NC mutations that accumulated during earlier passages of the HM-175 virus in primary AGMK cells appeared, independently and additively, to result in decreased biochemical evidence of hepatitis in tamarins. However, neither group of 5' NC mutations had a demonstrable effect on the extent of virus excretion or liver pathology in these animals. PMID:8892918

  14. Progress toward the development of a genetically engineered attenuated hepatitis A virus vaccine.

    PubMed

    Funkhouser, A W; Raychaudhuri, G; Purcell, R H; Govindarajan, S; Elkins, R; Emerson, S U

    1996-11-01

    Mutations which positively affect growth of hepatitis A virus in cell culture may negatively affect growth in vivo. Therefore, development of an attenuated vaccine for hepatitis A may require a careful balancing of mutations to produce a virus that will grow efficiently in cells suitable for vaccine production and still maintain a satisfactory level of attenuation in vivo. Since such a balance could be achieved most directly by genetic engineering, we are analyzing mutations that accumulated during serial passage of the HM-175 strain of hepatitis A virus in MRC-5 cell cultures in order to determine the relative importance of the mutations for growth in MRC-5 cells and for attenuation in susceptible primates. Chimeric viral genomes of the HM-175 strain were constructed from cDNA clones derived from a virulent virus and from two attenuated viruses adapted to growth in African green monkey kidney (AGMK) and MRC-5 cells, respectively. Viruses encoded by these chimeric genomes were recovered by in vitro or in vivo transfection and assessed for their ability to grow in cultured MRC-5 cells or to cause hepatitis in primates (tamarins). The only MRC-5-specific mutations that substantially increased the efficiency of growth in MRC-5 cells were a group of four mutations in the 5' noncoding (NC) region. These 5' NC mutations and a separate group of 5' NC mutations that accumulated during earlier passages of the HM-175 virus in primary AGMK cells appeared, independently and additively, to result in decreased biochemical evidence of hepatitis in tamarins. However, neither group of 5' NC mutations had a demonstrable effect on the extent of virus excretion or liver pathology in these animals.

  15. The Radio Spectral Energy Distribution and Star-formation Rate Calibration in Galaxies

    NASA Astrophysics Data System (ADS)

    Tabatabaei, F. S.; Schinnerer, E.; Krause, M.; Dumas, G.; Meidt, S.; Damas-Segovia, A.; Beck, R.; Murphy, E. J.; Mulcahy, D. D.; Groves, B.; Bolatto, A.; Dale, D.; Galametz, M.; Sandstrom, K.; Boquien, M.; Calzetti, D.; Kennicutt, R. C.; Hunt, L. K.; De Looze, I.; Pellegrini, E. W.

    2017-02-01

    We study the spectral energy distribution (SED) of the radio continuum (RC) emission from the Key Insight in Nearby Galaxies Emitting in Radio (KINGFISHER) sample of nearby galaxies to understand the energetics and origin of this emission. Effelsberg multi-wavelength observations at 1.4, 4.8, 8.4, and 10.5 GHz combined with archive data allow us, for the first time, to determine the mid-RC (1–10 GHz, MRC) bolometric luminosities and further present calibration relations versus the monochromatic radio luminosities. The 1–10 GHz radio SED is fitted using a Bayesian Markov Chain Monte Carlo technique leading to measurements for the nonthermal spectral index ({S}ν ∼ {ν }-{α {nt}}) and the thermal fraction ({f}{th}) with mean values of {α }{nt}=0.97 +/- 0.16(0.79 +/- 0.15 for the total spectral index) and {f}{th} = (10 ± 9)% at 1.4 GHz. The MRC luminosity changes over ∼3 orders of magnitude in the sample, 4.3× {10}2 {L}ȯ < MRC < 3.9× {10}5 {L}ȯ . The thermal emission is responsible for ∼23% of the MRC on average. We also compare the extinction-corrected diagnostics of the star-formation rate (SFR) with the thermal and nonthermal radio tracers and derive the first star-formation calibration relations using the MRC radio luminosity. The nonthermal spectral index flattens with increasing SFR surface density, indicating the effect of the star-formation feedback on the cosmic-ray electron population in galaxies. Comparing the radio and IR SEDs, we find that the FIR-to-MRC ratio could decrease with SFR, due to the amplification of the magnetic fields in star-forming regions. This particularly implies a decrease in the ratio at high redshifts, where mostly luminous/star-forming galaxies are detected.

  16. Homography-Based Correction of Positional Errors in MRT Survey

    NASA Astrophysics Data System (ADS)

    Nayak, A.; Daiboo, S.; Udaya Shankar, N.

    2009-09-01

    The Mauritius Radio Telescope (MRT) images show systematics in the positional errors of sources when compared to source positions in the Molonglo Reference Catalogue (MRC). We have applied two-dimensional homography to correct positional errors in the image domain and avoid re-processing the visibility data. Positions of bright (above 15 σ) sources, common to MRT and MRC catalogues, are used to set up an over-determined system to solve for the 2-D homography matrix. After correction, the errors are found to be within 10% of the beamwidth for these bright sources and the systematics are eliminated from the images.

  17. A subspace-based parameter estimation algorithm for Nakagami-m fading channels

    NASA Astrophysics Data System (ADS)

    Dianat, Sohail; Rao, Raghuveer

    2010-04-01

    Estimation of channel fading parameters is an important task in the design of communication links such as maximum ratio combining (MRC). The MRC weights are directly related to the fading channel coefficients. In this paper, we propose a subspace based parameter estimation algorithm for the estimation of the parameters of Nakagami-m fading channels in the presence of additive white Gaussian noise. Comparisons of our proposed approach are made with other techniques available in the literature. The performance of the algorithm with respect to the Cramer-Rao bound (CRB) is investigated. Computer simulation results for different signal to noise ratios (SNR) are presented.

  18. Determination of functional prognosis in hospitalized patients following an intensive care admission

    PubMed Central

    Ferreira, Natália A; Lopes, Agnaldo José; Ferreira, Arthur S; Ntoumenopoulos, George; Dias, Jerffesson; Guimaraes, Fernando S

    2016-01-01

    AIM To investigate the factors associated with the functional progress of hospitalized patients following an intensive care admission. METHODS Retrospective study including data from a cohort of 198 hospitalized patients following an intensive care admission and not requiring mechanical ventilation in a single tertiary referral hospital. A generalized linear model was used to identify the main effects of clinical and demographic variables on the outcomes of functionality (KATZ Index of Independence in Activities of Daily Living) and muscle strength (MRC Scale). The covariates identified as independent predictors were analysed using the receiver operating characteristic curves. The analysis differentiated the periods in the intensive care unit (ICU), in the Ward (WARD) and the total time of hospital stay (TOT). RESULTS Considering the functional outcome (ΔKATZ), the variables that significantly contributed to the model (P < 0.05) were the KATZ and MRC on admission, age, sepsis (no), and total length of stay (TLS). Regarding the muscle strength outcome model (ΔMRC), the predictors were MRC on admission, Simplified Acute Physiology Score III, previous stroke, TLS, and sex (female). The variable age (AUC = 0.664) discriminated the ΔKATZICU. The variables age (AUC = 0.712), KATZ in ICU (AUC = 0.590) and on ward admission (AUC = 0.746), and MRC on ward admission (AUC = 0.721) were discriminative for ΔKATZWARD. For ΔKATZTOT the variables KATZ on ICU admission (AUC = 0.621) and TLS (AUC = 0.617) were discriminative. For ΔMRCICU the variables SAPSIII (AUC = 0.661) and MRC on ICU admission (AUC = 0.653) were discriminative. MRC on ICU (AUC = 0.681) and ward admission (AUC = 0.553) were discriminative for ΔMRCWARD. TLS (AUC = 0.649) and MRC on ward admission (AUC = 0.696) discriminative for the ΔMRCTOT. CONCLUSION Specific functional, clinical and demographical variables at ICU admission are associated with the functional prognosis during the hospitalization period

  19. SOAR: Space Orbiting Advanced Fusion Power Reactor.

    DTIC Science & Technology

    1987-09-01

    this are the possibility of electrostatic direct conversion and the ease of increasing magnetic fields to maintain plasma pressure . The gene- ral...106 0.2 29 290 Known Reserves 3 x 103 0.2 187 1870 MAN-MADE U.S. DOE MRC Sales 1.3/yr MRC Inventory 13.4 CANDU Reactors (by year 2000) Production 2/yr...Research Corp. currently sells up to 1.3 kg/yr and has a 13 kg inventory. The Canadian CANDU reactors produce tritium in their D20 moderators. By 1987, 5

  20. The F100 Engine Purchasing and Supply Chain Management Demonstration: Findings from Air Force Spend Analyses

    DTIC Science & Technology

    2006-01-01

    spend for both spares and repairs went to the top five suppli- ers (see Table 4.1). Only two of the five, AB SKF and MPB Corpora- tion (Timken),3 were...tracts Number of NSNsa 1 United Technologies Corp. 3.8 37 96 4 16 2 AB SKF (MRC Bearings)b 1.6 16 13 10 9 3 MPB Corp. (Timken)b 1.5 15 3 5 5 4 Canadian...of Dollars Spent with Sole- Source Contracts Num- ber of Con- tracts Number of NSNs 1 AB SKF (MRC Bearings)a 4.4 24 19 31 27 2 Honeywell

  1. Gerald Loewi: A Major Contributor to the New Era of Rheumatology Thinking

    PubMed Central

    Denman, Michael

    2017-01-01

    Dr Gerald Loewi was Senior Research Scientist and Consultant Pathologist at the Medical Research Council (MRC) Rheumatism Research Unit at Taplow, England and subsequently the MRC Clinical Research Centre, Harrow, England. An immunologist with a background in pathology, he made major contributions to our understanding of the immunopathology of rheumatoid arthritis and other rheumatic disorders. With his colleagues, he developed a more sophisticated concept of what were initially thought to be primary autoimmune or degenerative diseases but are now recognized as much more complex disease processes. He was one of the first to initiate close collaboration between clinicians and scientists in rheumatology research and practice. PMID:28178437

  2. A visual basic spreadsheet macro for recession curve analysis.

    PubMed

    Posavec, Kristijan; Bacani, Andrea; Nakić, Zoran

    2006-01-01

    A Visual Basic program for an Excel spreadsheet was written to construct a master recession curve (MRC), using the adapted matching strip method, for recession analysis of ground water level time series. The program uses five different linear/nonlinear regression models to adjust individual recession segments to their proper positions in the MRC. The program can also be used to analyze the recession segments of other time series, such as daily stream discharge or stage. Some examples of field data from Croatia are used to illustrate the usefulness of its application.

  3. 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...

  4. 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

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

    PubMed

    Stawicki, Piotr; Gembler, Felix; Volosyak, Ivan

    2016-01-01

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

  6. 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.

  7. Molecular anatomy of tunicate senescence: reversible function of mitochondrial and nuclear genes associated with budding cycles.

    PubMed

    Kawamura, Kaz; Kitamura, Seigo; Sekida, Satoko; Tsuda, Masayuki; Sunanaga, Takeshi

    2012-11-01

    Zooids of the asexual strain of Polyandrocarpa misakiensis have a lifespan of 4-5 months; before dying, they produce many buds, enabling continuation of the strain. This study was designed to investigate the nature of gene inactivation and reactivation during this continuous process of senescence and budding. During senescence, the zooidal epidermis showed acid β-galactosidase activity, lost proliferating cell nuclear antigen immunoreactivity and became ultrastructurally worn, indicating that the epidermis is a major tissue affected by the ageing process. Semi-quantitative PCR analysis showed that the genes encoding mitochondrial respiratory chains (MRCs) engaged in decreased transcriptional activity in senescent adults compared with younger adults. The results of in situ hybridization showed that the epidermis dramatically attenuates MRC expression during ageing but restores gene activity when budding commences. During budding and ageing, the nuclear gene Eed (a polycomb group component) was activated and inactivated in a pattern similar to that observed in MRCs. In buds, RNA interference (RNAi) of Eed attenuated Eed transcripts but did not affect the gene expression of pre-activated MRCs. A tunicate humoral factor, TC14-3, could induce Eed, accompanying the reactivation of MRC in adult zooids. When RNAi of Eed and Eed induction were performed simultaneously, zooidal cells and tissues failed to engage in MRC reactivation, indicating the involvement of Eed in MRC activation. Results of this study provide evidence that the mitochondrial gene activities of Polyandrocarpa can be reversed during senescence and budding, suggesting that they are regulated by nuclear polycomb group genes.

  8. 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.

  9. 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

  10. 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.

  11. 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

  12. 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...

  13. 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…

  14. Focused Magnetic Resonance Coupling Coils for Electromagnetic Therapy Applications.

    PubMed

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

    2015-11-01

    This paper presents the design and construction of a pair of figure-of-eight coils, coupled by magnetic resonance coupling (MRC), which could generate (150 V/m per Ampere) electric field at the focal points for electromagnetic therapy related applications. The E field generated at the targeted site would be significantly enhanced under the same amount of current flowing through the MRC figure-of-eight coils compared to normal coils, due to the superposition of E field contributed by the coils. Furthermore, the MRC figure-of-eight coil is designed and the results are verified in theory, simulation, and experiments. In the ex vivo tissue measurement, 35% current and 82% ohmic power improvements were observed. Since it can enhance the current and ohmic power, the MRC figure-of-eight coils are promising solutions for electromagnetic therapy applications. The potential applications of the coils include noninvasive radio frequency (RF) stimulation, thermoacoustic imaging, electromagnetic field therapies, and RF ablation, etc.

  15. 77 FR 70443 - Agency Information Collection Activities; Submission to OMB for Review and Approval; Public...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-11-26

    ...), described below, to the Office of Management and Budget (OMB) for review and approval. The ICR is for... the MRC units in communities across the United States, and to continue planning for future emergencies... develop, acquire, install and utilize technology and systems for the purpose of collecting, validating...

  16. 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

  17. 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 student/counselors…

  18. 78 FR 75659 - Self-Regulatory Organizations; The Options Clearing Corporation; Order Approving Proposed Rule...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-12-12

    ... Change Concerning Charters for the Board of Directors, the Membership/Risk Committee, the Audit Committee... charter of OCC's Board of Directors (``Board''), as well as the charters of the Board's Membership/Risk Committee (``MRC''), Audit Committee (``AC''), and Performance Committee (``PC'') (collectively,...

  19. 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…

  20. An Analysis of IEEE 802.11B and 802.16 Technologies as Part of the Tactical Internet

    DTIC Science & Technology

    2005-09-01

    MANET, MESH, C2PC, C2CE, 802.16, WIMAX, OFDM , COTS, Common Operational Picture, Common Tactical Picture, WLAN, Bridging, Tactical Internet, PRC- 119...19 a. AN/MRC-142 Digital Wideband Transmission System ( DWTS ...63 B. HARRIS CORPORATION’S IEEE 802.11B BASED SECNET-11 PRODUCTS

  1. 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...

  2. Prooxidant action of chebulinic acid and tellimagrandin I: causing copper-dependent DNA strand breaks.

    PubMed

    Yi, Zong-Chun; Liu, Yan-Ze; Li, Hai-Xia; Wang, Zhao

    2009-04-01

    The prooxidant activity of two hydrolysable tannins, chebulinic acid and tellimagrandin I, on plasmid DNA and genomic DNA of cultured MRC-5 human embryo lung fibroblasts was assessed. The results revealed that both hydrolysable tannins in combination with Cu(II) induced DNA strand breaks in pBR322 plasmid DNA in a concentration-dependent manner. Chebulinic acid and tellimagrandin I also induced genomic DNA strand breaks of MRC-5 human embryo lung fibroblasts in the presence of Cu(II). After treatment with chebulinic acid or tellimagrandin I alone, the pBR322 plasmid DNA and genomic DNA in MRC-5 cells kept intact. In addition, addition of Cu(I) reagent bathocuproinedisulfonic acid or catalase markedly inhibited the copper-dependent DNA strand breaks by both tannins. However, three typical hydroxyl radical scavengers, DMSO, ethanol and mannitol, did not inhibit the DNA strand breaks. Both tannins were able to reduce Cu(II) to Cu(I). These results indicated that chebulinic acid and tellimagrandin I induced the copper-dependent strand breaks of pBR322 plasmid DNA and MRC-5 genomic DNA with prooxidant action, in which Cu(II)/Cu(I) redox cycle and H(2)O(2) were involved and hydroxyl radical formation is important in the hypothetical mechanism by which DNA strand breaks are formed.

  3. Pre- and postprocessing for multilayer compression of scanned documents

    NASA Astrophysics Data System (ADS)

    Zaghetto, Alexandre; de Queiroz, Ricardo L.

    2011-10-01

    The mixed raster content (MRC) document-compression standard (ITU T.44) specifies a multilayer representation of a document image. The model is very efficient for representing sharp text and graphics over a background. However, its binary selection layer compromises the representation of scanned data and soft edges. Typical segmentation algorithms that split up the document into layers tend to lift letter colors to the foreground, so that soft edge transitions may not fully belong either to the foreground or background layers, causing ``halos'' around objects that impair compression performance. We present a method that sharpens the document before compression and softens its edges after MRC-based reconstruction. It builds an edge-sharpening map and estimates the original edge softness at the encoder. The generated map and softness parameters are then used to reconstruct the original soft edges at the decoder. An MRC encoding and decoding scheme based on H.264/AVC and JBIG2 has been used. Experimental results show that, for lower bit rates, the proposed pre-/postprocessing method can improve both subjective and objective compression performance over regular MRC.

  4. Evaluation of the Tobacco Heating System 2.2. Part 6: 90-day OECD 413 rat inhalation study with systems toxicology endpoints demonstrates reduced exposure effects of a mentholated version compared with mentholated and non-mentholated cigarette smoke.

    PubMed

    Oviedo, Alberto; Lebrun, Stefan; Kogel, Ulrike; Ho, Jenny; Tan, Wei Teck; Titz, Bjoern; Leroy, Patrice; Vuillaume, Gregory; Bera, Monali; Martin, Florian; Rodrigo, Gregory; Esposito, Marco; Dempsey, Ruth; Ivanov, Nikolai V; Hoeng, Julia; Peitsch, Manuel C; Vanscheeuwijck, Patrick

    2016-11-30

    The toxicity of a mentholated version of the Tobacco Heating System (THS2.2M), a candidate modified risk tobacco product (MRTP), was characterized in a 90-day OECD inhalation study. Differential gene and protein expression analysis of nasal epithelium and lung tissue was also performed to record exposure effects at the molecular level. Rats were exposed to filtered air (sham), to THS2.2M (at 15, 23 and 50 μg nicotine/l), to two mentholated reference cigarettes (MRC) (at 23 μg nicotine/l), or to the 3R4F reference cigarette (at 23 μg nicotine/l). MRCs were designed to meet 3R4F specifications. Test atmosphere analyses demonstrated that aldehydes were reduced by 75%-90% and carbon monoxide by 98% in THS2.2M aerosol compared with MRC smoke; aerosol uptake was confirmed by carboxyhemoglobin and menthol concentrations in blood, and by the quantities of urinary nicotine metabolites. Systemic toxicity and alterations in the respiratory tract were significantly lower in THS2.2M-exposed rats compared with MRC and 3R4F. Pulmonary inflammation and the magnitude of the changes in gene and protein expression were also dramatically lower after THS2.2M exposure compared with MRCs and 3R4F. No menthol-related effects were observed after MRC mainstream smoke-exposure compared with 3R4F.

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

    ERIC Educational Resources Information Center

    Huertas, Aurelio, Jr.; Sullivan, Carol

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

  6. Acylated pregnane glycosides from Caralluma tuberculata and their antiparasitic activity.

    PubMed

    Abdel-Sattar, Essam; Harraz, Fathalla M; Al-ansari, Soliman Mohammed Abdullah; El-Mekkawy, Sahar; Ichino, Chikara; Kiyohara, Hiroaki; Ishiyama, Aki; Otoguro, Kazuhiko; Omura, Satoshi; Yamada, Haruki

    2008-08-01

    Five pregnane glycosides were isolated from Caralluma tuberculata (1-5), in addition to a known one (russelioside E, 6). The structures of the isolated compounds were elucidated by the analysis of NMR data and FAB-MS experiments. All the isolated compounds were tested for their antimalarial and antitrypanosomal activities as well as their cytotoxicity against human diploid embryonic cell line (MRC5).

  7. 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…

  8. 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.

  9. 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.

  10. The MORPHEUS protein crystallization screen.

    PubMed

    Gorrec, Fabrice

    2009-12-01

    A 96-condition initial screen for protein crystallization, called MORPHEUS, has been developed at the MRC Laboratory of Molecular Biology, Cambridge, England (MRC-LMB). The concept integrates several innovative approaches, such as chemically compatible mixes of potential ligands, new buffer systems and precipitant mixes that also act as cryoprotectants. Instead of gathering a set of crystallization conditions that have already been successful, a selection of molecules frequently observed in the Protein Data Bank (PDB) to co-crystallize with proteins has been made. These have been put together in mixes of similar chemical behaviour and structure, and combined with buffers and precipitant mixes that were also derived from PDB searches, to build the screen de novo. Observations made at the MRC-LMB and many practical aspects were also taken into account when formulating the screen. The resulting screen is easy to use, comprehensive yet small, and has already yielded a list of crystallization hits using both known and novel samples. As an indicator of success, the screen has now become one of the standard screens used routinely at the MRC-LMB when searching initial crystallization conditions for biological macromolecules.

  11. Identifying adults at risk of COPD who need confirmatory spirometry in primary care

    PubMed Central

    Hill, Kylie; Hodder, Richard; Blouin, Maria; Heels-Ansdell, Diane; Guyatt, Gordon; Goldstein, Roger

    2011-01-01

    Abstract Objective To examine the usefulness of a symptom-based case-finding questionnaire (CFQ) and the Medical Research Council (MRC) dyspnea scale in identifying which individuals with known risk factors for chronic obstructive pulmonary disease (COPD) require targeted spirometry in primary care. Design Cross-sectional study. Setting Three community primary care practices in Ontario. Participants Men and women 40 years of age and older with a smoking history of 20 pack-years or more. Main outcome measures We administered a CFQ for the presence of cough, sputum, wheeze, dyspnea, and recurrent respiratory infections (possible range of scores from 0 to 5) and applied the MRC dyspnea scale to assess the severity of COPD (possible range of scores from 1 to 5). Spirometric measures of forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) were collected, with COPD defined as a postbronchodilator FEV1/FVC of less than 0.7 and FEV1 of less than 80% of the predicted value. Using spirometric data to confirm the diagnosis of COPD, likelihood ratios, pretest and posttest probabilities, and area under a receiver operating characteristic curve were calculated for the total CFQ and MRC scores. Results Scores for the CFQ and MRC dyspnea scale were available for 996 and 829 participants, respectively. The likelihood ratios for a total CFQ score of 3 or higher and an MRC dyspnea score of 4 or 5 were 1.82 (95% confidence interval [CI] 1.48 to 2.22) and 4.22 (95% CI 2.08 to 8.56), respectively. The likelihood ratios for a total CFQ score of 2 or less and an MRC dyspnea score of 1 were 0.75 (95% CI 0.66 to 0.85) and 0.50 (95% CI 0.39 to 0.65), respectively. Area under the receiver operating characteristic curve was 0.62 (95% CI 0.58 to 0.67; P < .001) for the total CFQ scores and 0.64 (95% CI 0.60 to 068; P < .001) for the MRC dyspnea scores. Conclusion In adults with known risk factors, the likelihood of having moderate to severe COPD is increased in those who

  12. Production mask composition checking flow

    NASA Astrophysics Data System (ADS)

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

    2016-05-01

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

  13. Magnetic resonance colonography without bowel cleansing: a prospective cross sectional study in a screening population

    PubMed Central

    Kuehle, Christiane A; Langhorst, Jost; Ladd, Susanne C; Zoepf, Thomas; Nuefer, Michael; Grabellus, Florian; Barkhausen, Joerg; Gerken, Guido; Lauenstein, Thomas C

    2007-01-01

    Background and aim To evaluate the diagnostic accuracy of magnetic resonance colonography (MRC) without bowel cleansing in a screening population and compare the results to colonoscopy as a standard of reference. Methods 315 screening patients, older than 50 years with a normal risk profile for colorectal cancer, were included in this study. For MRC, a tagging agent (5.0% Gastrografin, 1.0% barium sulphate, 0.2% locust bean gum) was ingested with each main meal within 2 days prior to MRC. No bowel cleansing was applied. For the magnetic resonance examination, a rectal water enema was administered. Data collection was based on contrast enhanced T1 weighted images and TrueFISP images. Magnetic resonance data were analysed for image quality and the presence of colorectal lesions. Conventional colonoscopy and histopathological samples served as reference. Results In 4% of all colonic segments, magnetic resonance image quality was insufficient because of untagged faecal material. Adenomatous polyps >5 mm were detected by means of MRC, with a sensitivity of 83.0%. Overall specificity was 90.2% (false positive findings in 19 patients). However, only 16 of 153 lesions <5 mm and 9 of 127 hyperplastic polyps could be visualised on magnetic resonance images. Conclusions Faecal tagging MRC is applicable for screening purposes. It provides good accuracy for the detection of relevant (ie, adenomatous) colorectal lesions >5 mm in a screening population. However, refinements to optimise image quality of faecal tagging are needed. PMID:17341542

  14. 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

  15. Dengue type 4 live-attenuated vaccine viruses passaged in vero cells affect genetic stability and dengue-induced hemorrhaging in mice.

    PubMed

    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-Q(438)H, E-V(463)L, NS2B-Q(78)H, and NS2B-A(113)T 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.

  16. Efficacy and tolerability of different brands of intravenous immunoglobulin in the maintenance treatment of chronic immune-mediated neuropathies.

    PubMed

    Gallia, Francesca; Balducci, Claudia; Nobile-Orazio, Eduardo

    2016-06-01

    High-dose intravenous immunoglobulin (IVIg) is effective in chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and multifocal motor neuropathy (MMN). Not all brands of IVIg are however licensed for these neuropathies. We reviewed six patients with CIDP and seven with MMN treated with maintenance therapy with IVIg from 2009 to 2013. In all patients, we measured the Medical Research Council (MRC) and Overall Neuropathy Limitation Scale (ONLS) scores before each infusion, registered the monthly dose and brand of IVIg, and recorded adverse events. Patients were treated for 25-60 months (mean 49 months) alternating different brands of IVIg including IgVena, Gammagard, Kiovig, and Flebogamma. Minor and transient side effects were equally observed with each brand. No difference in the MRC or ONLS scores was observed in relation to the brand of IVIg used. Chronic maintenance treatment with IVIg in patients with MMN and CIDP was not associated with a different tolerability or efficacy despite the use of different brands of IVIg.

  17. 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.

  18. In Vitro Anti-Cytomegalovirus Activity of Kampo (Japanese Herbal) Medicine

    PubMed Central

    2004-01-01

    We examined the effect of three types of Kampo medicines on human cytomegalovirus (CMV) replication in the human embryonic fibroblast cell line, MRC-5. Treatment of cells with at least 0.01 μg/ml of Kampo medicines inhibited the cytopathic effects of CMV-infected MRC-5 cells. Moreover, Kampo medicine decreased the replication of CMV without affecting the inhibition of host cells, with a concomitant decrease in CMV DNA levels. However, Kampo medicine demonstrated no virocidal effect on cell-free CMV. Furthermore, western blotting analysis demonstrated that the Kampo medicine decreased the amount of 65 kDa late antigen expression in the infected cells. These results suggest that Kampo medicine may be sufficient to inhibit viral DNA replication and late protein synthesis, resulting in anti-CMV effects. Therefore, these three Kampo medicines have the potential of being a source of new powerful anti-CMV compounds. PMID:15841262

  19. Performance analysis of generalized QAM modulation under η-μ and κ-μ fading

    NASA Astrophysics Data System (ADS)

    L Queiroz, Wamberto J.; Madeiro, Francisco; A Lopes, Waslon T.; Alencar, Marcelo S.

    2013-12-01

    This paper presents new closed-form expressions for the symbol error probability (SEP) of θ-QAM modulation with maximum ratio combining (MRC) receiver under η- μ and κ- μ fading. The SEP formulae, obtained from the definite integrals of the moment generating function (MGF) of the signal-to-noise ratio (SNR) at the input of the MRC receiver, are written in terms of Lauricella functions. The numerical evaluation of the expressions is carried out for the η- μ distribution, which includes important distributions as special cases, such as Hoyt, Nakagami- m, Rayleigh, and one-sided Gaussian, as well as for the κ- μ distribution, which includes Rice, Nakagami- m, Rayleigh, and one-sided Gaussian as special cases.

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

    PubMed

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

    2014-05-19

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

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    2002-01-01

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

  3. Oscillatory Instability in a Two-Fluid Benard Problem.

    DTIC Science & Technology

    1984-04-01

    1963-A ( MRC Technical Summary Report #2681 OSCILLATORY INSTABILITY IN Ar TWO-FLUID BENARD PROBLEM CV Yuriko Renardy and Daniel D. Joseph 4.o...MATHEMATICS RESEARCH CENTER OSCILLATORY INSTABILITY IN A TWO-FLUID BENARD PROBLEM Yuriko Renardy I and Daniel D. Joseph * ’ 2 Technical Summary Report #2681...C. ° * .* * .* • * . -t . . . . .. . . . " -".- ." . o ,- OSCILLATORY INSTABILITY IN A WO-FLUID BENARD PROBLEM Yuriko RenardyI and Daniel D

  4. 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

  5. Processing of Novel Nanoparticle Dispersion Strengthened Ceramics for Improved Mechanical Performance

    DTIC Science & Technology

    1993-12-14

    A2751 1 965 Eeto liii Optics MRC Materials Education M CLiaison Program Mchanical Polymers Behavior SECOND ANNUAL REPORT PROCESSING OF NOVEL...NANOPARTICLE DISPERSION STRENGTHENE D CERAMICS FOR IMPROVED MECHANICAL PE RFORMANCE Professors 11. M . Chan, (P.1.), M . P. Harmer (Co-P.I.), ___ and...Institute ONR Grant No.: N00014-92-J-1635 Mod. P00002 EPRI Contract: RP2426-54 Amend. 1 Re ,ort Period: 15 December 1992 - 14 December 1993 M ateral R

  6. Oxidative capacities of cardiac and skeletal muscles of heart transplant recipients: mitochondrial effects of cyclosporin-A and its vehicle Cremophor-EL.

    PubMed

    N' Guessan, Benoit Banga; Sanchez, Hervé; Zoll, Joffrey; Ribera, Florence; Dufour, Stéphane; Lampert, Eliane; Kindo, Michel; Geny, Bernard; Ventura-Clapier, Renée; Mettauer, Bertrand

    2014-04-01

    Chronic immunosuppressive treatment was suspected to alter maximal muscle oxidative capacity (Vmax ) of heart transplant recipients, leading to a limitation of their exercise tolerance. It remains undefined whether the mitochondrial respiratory chain (MRC) of right ventricle (RV) and vastus lateralis (VL) muscles were altered by immunosuppressants and/or their vehicles. Vmax was measured polarographically in saponin-skinned fibres of RV and VL biopsies of patients and compared with Vmax of healthy VL and myocardium. Effects of increasing concentrations (1-10-100 μM) of Sandimmune(®) , its vehicle, Cyclosporine (CsA) in ethanol (EtOH), or EtOH alone were tested. The vehicle's effects on MRC complexes were investigated using specific substrates and inhibitors. Ten months after grafting, Vmax of RV and VL of immunosuppressed patients were similar to their Vmax at time of transplantation and to that of control tissues. In Vitro, Sandimmune(®) significantly decreased Vmax while CsA in EtOH or EtOH exerted small and similar effects. Effects of the vehicle were higher than (RV) or identical to (VL) those of Sandimmune(®) . The sites of action of the vehicle on MRC were located on complexes I and IV. While unchanged under chronic immunosuppressive therapy, Vmax of RV and VL muscles was depressed by acute exposure to intravenous Sandimmune(®) in vitro, an effect attributed to its vehicle by inhibition of complexes I and IV of the MRC. This work provides an in vitro proof of a toxic effect on the mitochondria respiratory chain of the vehicle used in the intravenous formulation of Sandimmune(®) but with no clinical consequences in chronically immunosuppressed patients.

  7. Communication Control and Leadership in Telecommunications by Small Groups.

    DTIC Science & Technology

    1980-06-01

    used in this experiment (see section on Prob- lems). Dependent measures have generally included the time it takes groups to solve the problems, the... section , Questionnaire subsection). :. 10 HYPOTHESES Three main hypotheses were generated from the re- sults found in the literature: 1. Subjects who...similar to the MRC network. A decentralized network is provided by continuously open audio and video channels (see Method section , Switching subsection). 2

  8. Damage-based finite-element vertebroplasty simulations.

    PubMed

    Kosmopoulos, V; Keller, T S

    2004-11-01

    The objectives of this study were to quantify the efficacy of vertebroplasty according to: (1) damage and (2) cement quantity (fill) and modulus. Vertebral body damage was numerically simulated using a previously validated two-dimensional finite-element model coupled with an elasto-plastic modulus reduction (EPMR) scheme. The effects of cement fill (% marrow replaced by cement, % MRC) and cement modulus on vertebral apparent modulus and trabecular bone tissue stress concentrations were parametrically assessed for four EPMR damage models (19%, 33%, 60%, and 91% modulus reduction). For this analysis, the elastic modulus of the trabecular bone tissue and marrow elements were assumed to be 10 GPa and 10 kPa, respectively. The effect of cement modulus (varied in the range 1 GPa to 9 GPa) on vertebral apparent modulus was also examined for partial fill (39% MRC) and complete fill (100% MRC) using the 33% modulus reduction damage model. In the case of polymethylmethacrylate (PMMA cement modulus = 2.16 GPa), restoration of the thoracic vertebral body (T10) apparent modulus to undamaged levels required 71% and 100% cement fill for the 19-33% and 60-91% modulus reduction damage models, respectively. Variations in cement modulus had no appreciable effect on the recovery of vertebral apparent modulus to undamaged levels for simulations of partial cement fill (39% MRC). For complete cement fill, however, a PMMA cement modulus produced approximately a 2-fold increase (82%) in vertebral apparent modulus relative to the undamaged vertebral body. Increasing the cement modulus to 9 GPa increased the vertebral apparent modulus over 2.5-fold (158%) relative to the undamaged state. The EPMR damage scheme and repair simulations performed in this study will help clinicians and cement manufacturers to improve vertebroplasty procedures.

  9. Laboratory Evaluation of Australian Ration Packs

    DTIC Science & Technology

    1988-10-01

    described in Official Methods of Analysis of the Association of Official Analytical Chemists ( AOAC , 1980). Fat was determined in sweetened condensed milk...reviewed. 10 7. REFERENCES Anon (1982) "Dietary guidelines for Australians" J. Fd Nutr., 38, 111-119. AOAC , (1980) Official Methods of Analysis of the...Research Council (NH & MRC, 1984). The Reference Man is 70 kg and has the requirements for various grades of activity listed in Table 2. 2. METHODS OF

  10. 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

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

    PubMed Central

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

    2015-01-01

    To ensure correct DNA replication, eukaryotes have signaling pathways that respond to replication-associated DNA damage and trigger repair. In both Saccharomyces cerevisiae and Schizosaccharomyces pombe, a complex of proteins, including the cullin protein Rtt101p and two adapter proteins Mms22p and Mms1p, is important for proper response to replication stress. We have investigated this system in Candida albicans. In this pathogen, Mms22p is important for recovery from DNA replication damage induced by agents including methylmethane sulfonate, camptothecin, and ionizing radiation. Although no clear ortholog of Mms1p has been identified in C. albicans, loss of either Mms22p or Rtt101p generates similar damage sensitivity, consistent with a common function. In S. cerevisiae, the Mrc1p−Csm3p−Tof1p complex stabilizes stalled replication forks and activates a replication checkpoint and interacts with Mms22p. A similar complex in S. pombe, consisting of the Tof1p and Csm3p orthologs Swi1p and Swi3p, along with the fission yeast Mrc1p, genetically also interacts with Mms22p. Intriguingly in C. albicans only Mrc1p and Csm3p appear involved in damage repair, and Mms22p is required for responding to DNA damage agents in MRC1 or CSM3 conditional mutants. In C. albicans, although the loss of RAD57 greatly impairs response in the pathogen to many DNA-damaging agents, lethality due to camptothecin damage requires concomitant loss of Rad57p and Mms22p, suggesting that Mms22p is only essential for homologous recombination induced by camptothecin. These results establish that although C. albicans uses conserved cellular modules to respond to DNA damage and replication blocks, the specific details of these modules differ significantly from the S. cerevisiae model. PMID:26438292

  12. Advanced Microwave Ferrite Research (AMFeR): Phase Four

    DTIC Science & Technology

    2009-10-15

    COVERED (From - To) 28 Dec 2006 - 30 Sep 2009 4. TITLE AND SUBTITLE Advanced Microwave Ferrite Research (AMFeR): Phase Four 5a. CONTRACT NUMBER 5b...research endeavor is to devise ferrite materials for microwave , self-biased circulator applications. To this end, the research team focused on two key...Std Z39-18 Final Report Advanced Microwave Ferrite Research (AMFeR): Phase Four Dr. Jeffrey L. Young MRC Institute/Electrical and Computer

  13. Area Handbook Series: Argentina: A Country Study

    DTIC Science & Technology

    1985-08-01

    Intrasigencia y Movilizaciön MIM (Intransigence and Mobilization Movement) Movimiento de Renovaciön y Cambio MRC (Movement of Renovation and Change...Argentine Industrial Union) Government Agencies Comisiön Nacional de Energia Atomica CNEA (National Atomic Energy Commission) Comisiön Nacional... renovation of their cadres, and by alienating its political leadership from both the old clans and the leaders of the new families of money and education

  14. 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

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

    PubMed

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

    2003-05-01

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

  16. Maintaining Enterprise Resiliency via Kaleidoscopic Adaption and Transformation of Software Services (MEERKATS)

    DTIC Science & Technology

    2016-04-01

    critical components of today’s web services. We discuss these in Section 4.7. We believe that the cloud resilience technologies we have developed over...MOTAG. Our moving target defense mechanism defends both authenticated services and open web services from Internet DDoS attacks. Our mechanism...Resilient Cloud (MRC) program we developed moving target defenses for both open and general-purpose web services as well as security sensitive online

  17. The Interfaces of One-Dimensional Flows in Porous Media.

    DTIC Science & Technology

    1983-07-01

    MRC-TSR-2538 DAAG2N-80-C-0041 UNCLASSIFIED FIG 12/1 N lm . 1.25 1.4 16 MICROCOY RESOLUTION TEST CHART sNarOAI.I U(’ OV $t MOAAI9 - -A A1 NRC Technical...Words: flows in porous media, interfaces, blow-up time, waiting time, asymptotic behaviour Work Unit Number 1 (Applied Analysis) D1 )iv. Matematicas

  18. The Role of Ellipticity and Normality Assumptions in Formulating Live-Boundary Conditions in Elasticity.

    DTIC Science & Technology

    1985-02-01

    111l11.4 11 1.6 MICROCOPY RESOLUTION TEST CHART NATIONAL BUREAU Of S[ANDARDS 963-4 I 4 . . MRC Technical Summary Report #27H8 - It THE ROLE OF...UniversitA di Roma-Tor Vergata, 00173 Roma, Italy. ** Dipartimento di Matematica , UniversitA di Pisa, 56100 Pisa, Italy. ***Dipartimento di...Roma-Tor Vergata, 00173 Roma, Italy. ** Dipartimento di Matematica , Universith di Pisa, 56100 Pisa, Italy. ***Dipartimento di Ingegneria Aerospaziale

  19. The Impact of Changes in State Identity on Alliance Cohesion in Northeast Asia

    DTIC Science & Technology

    2009-12-01

    School, Sun Zhe at Tsinghua University, and Zhan Debin at Fudan University, began to publicly express their new perceptions of the capabilities...Rin 4 al Hong Xuezhi 1 henyang MRC Wang Ke General Kim Hak Sam 994 DDM Kim Jong Kak COGS Choe Kwang General Oh Yong Bang 5 S 1995 MDN DFAB Sun...Qixiang AMS PC Zhang Gong Guangzhou MRPC Shi Yuxia DDM Kim Jong Kak 4 1996 ILD Deputy Director Dai Bingguo North Sea FC Wang Jiying

  20. 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.

  1. 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

  2. MATRIS Indexing and Retrieval Thesaurus (MIRT): Keyword Out of Context (KWOC)

    DTIC Science & Technology

    1994-08-01

    BREATHING Mrc 18 -B- I I I -- BRIDGE BRIDGE control systems Xeic BRIDGE control simulator Epqc i BRIGS Military BRIGS Feua I BROADCAST BROADCAST media Ys I I...CHANGE Gei Social CHANGE effects Fiqia CHANGES Social trends / CHANGES Bok CHANNELS Career promotion CHANNELS Fceg CHAPLAINRY Religious programs...m Attitudes of COMMUNITIES Mfem COMMUNITY I COMMUNITY / social -related factors Fiqi COMMUNITY relations skills Sim COMPANIES COMPANIES Gcka COMPANY

  3. VizieR Online Data Catalog: Gunn photometry of seven clusters of galaxies (Molinari+ 1996)

    NASA Astrophysics Data System (ADS)

    Molinari, E.; Buzzoni, A.; Chincarini, G.

    1996-04-01

    Gunn g, r, i photometry for the 7 clusters MRC0254-274, Cl0317+15, MS0418.3-3 844, Cl1141-283, A1689, A3594, S0781B is presented. For each cluster we derived the spatial distribution properties obtaining the core radius and the concentration parameters. Color properties of the cluster galaxy population are also briefly discussed. (7 data files).

  4. Phylogeography and genetic structure of the oriental river prawn Macrobrachium nipponense (Crustacea: Decapoda: Palaemonidae) in East Asia

    PubMed Central

    Chu, Ta-Jen; Lee, Ying-Chou

    2017-01-01

    The oriental river prawn (Macrobrachium nipponense) is mainly distributed in East Asia. The phylogeography, population genetic structure and historical demography of this species in the East Asia were examined by using partial sequences of the cytochrome oxidase subunit I (COI) and 16S rRNA in mitochondrial DNA. Ten populations that included 239 individuals were collected from Taiwan (Shihmen Reservoir, SMR, Mingte Reservoir, MTR and Chengching Lake Reservoir, CLR), mainland China (Taihu Lake, TLC, Min River, MRC, Jiulong River, JRC and Shenzhen Reservoir, SRC), Japan (Biwa Lake, BLJ and Kasumigaura Lake, KLJ) and Korea (Han River, HRK). The nucleotide diversity (π) of all individuals was 0.01134, with values ranging from 0.0089 (BLJ, Japan) to 0.01425 (MTR, Taiwan). A total of 83 haplotypes were obtained, and the haplotypes were divided into 2 main lineages: lineage A included the specimens from BLJ, KLJ, CLR, MTR, TLC, MRC and JRC, and lineage B comprised the ones from HRK, SRC, SMR, MTR, TLC, MRC and JRC. Lineage A could be further divided two sub-lineages (A1 and A2). Individuals of lineage A2 were only from TLC. Demographic expansion was observed in each lineage, starting within the second-to-latest interglacial period for lineage A and within the last glacial period for lineage B. All FST values among the ten populations were significantly different, except for the values between MRC and JRC, and SMR and SRC. The phylogeography and genetic structure of M. nipponense in East Asia might be influenced by Pleistocene glacial cycles, lake isolation and human introduction. The possible dispersal routes of M. nipponense in the East Asia were also discussed. PMID:28267807

  5. Production Team Maintenance: Systemic Constraints Impacting Implementation

    DTIC Science & Technology

    1997-05-01

    that may lend insight to factors inhibiting PTM implementation. Chapter four highlights alternatives and options that may improve implementation efforts...17). The two-MRC requirement is considered the "principal urgent diet " of the military. Efforts are focused on organizing, training, and equipping...maintenance AGS under the LG 1997: (Apr) CONUS C-130s realigned under AMC and AMOGs restructured The implementation of PTM followed suit--its structure

  6. Degenerate Systems of Conservation Laws.

    DTIC Science & Technology

    1985-09-01

    uI, ..., un ) u(x,t) , f " (fl’ "**’ fn) and x c R, t ) 0. Such equations arise in applications of gas dynamics, elasticity, oil reservoir ... simulation and other areas of engineering when diffusion is neglected. In solutions of (1), information travels at speeds Xi given by the eigenvalues of...laws which is not strictly hyperbolic", MRC Technical Summary Report #2184, December 29, 1980. [13] Peaceman, D. W., Fundamentals of Numerical Reservoir

  7. Can long-term thiamine treatment improve the clinical outcomes of myotonic dystrophy type 1?

    PubMed Central

    Costantini, Antonio; Trevi, Erika; Pala, Maria Immacolata; Fancellu, Roberto

    2016-01-01

    Myotonic dystrophy type 1, also known as Steinert's disease, is an autosomal dominant disorder with multisystemic clinical features affecting the skeletal and cardiac muscles, the eyes, and the endocrine system. Thiamine (vitamin B1) is a cofactor of fundamental enzymes involved in the energetic cell metabolism; recent studies described its role in oxidative stress, protein processing, peroxisomal function, and gene expression. Thiamine deficiency is critical mainly in the central and peripheral nervous system, as well as in the muscular cells. Our aim was to investigate the potential therapeutical effects of long-term treatment with thiamine in myotonic dystrophy type 1 in an observational open-label pilot study. We described two patients with myotonic dystrophy type 1 treated with intramuscular thiamine 100 mg twice a week for 12 or 11 months. We evaluated the patients using the grading of muscle strength according to Medical Research Council (MRC), the Muscular Impairment Rating Scale (MIRS), and the Modified Barthel index. High-dose thiamine treatment was well tolerated and effective in improving the motor symptomatology, particularly the muscle strength evaluated with the MRC scale, and the patients’ activities of daily living using the Modified Barthel Index. At the end of treatment, the MRC score was 5 in the proximal muscles and 2–4 in the distal muscles (the MRC score before the treatment was 3–4 and 1–3, respectively). The MIRS grade improved by 25% compared to baseline for both patients. In patient #1, the Modified Barthel Index improved by 44%, and in patient #2 by 29%. These findings suggest that clinical outcomes are improved by long-term thiamine treatment. PMID:27857755

  8. Combining cell lines to optimize isolation of human enterovirus from clinical specimens: report of 25 years of experience.

    PubMed

    Prim, Núria; Rodríguez, Graciela; Margall, Núria; Del Cuerpo, Margarita; Trallero, Gloria; Rabella, Núria

    2013-01-01

    Cell culture is still the gold standard for the diagnosis of human enteroviruses (HEVs) although molecular techniques are required for detection of some serotypes. Due to the diversity of HEVs, a single cell line is not susceptible to all serotypes, and several lines are required to optimize the isolation of HEVs. In this study, the results of HEV isolation during the last 25 years are reported. A total of 1,192 HEVs were isolated and isolation rates varied depending on the cell line used. MRC5 cells yielded the best results (70.7%), followed by A549 cells (52.6%), RD cells (37.5%), and HEp-2 cells (29.7%). A total of 521 HEVs were characterized, and HEV-B was the most frequent species (81%). Polioviruses (PV) and HEV-A were isolated less frequently (17% and 1%, respectively). None of the cell lines detected all the enteroviruses. MRC5 cells were the most susceptible for isolation of echoviruses (85.7%) and PVs (85.4%), whereas HEp2 was the most susceptible for Coxsackieviruses B (82.6%). Some serotypes were isolated in one cell line only. 40.5% of echoviruses were isolated in MRC5 cells whereas 42.3% and 23.9% of Coxsackieviruses B were isolated in RD cells and HEp2 cells, respectively. Although A549 cells did not achieve the best performance for any enterovirus serotypes, they isolated 52.6% of the total HEVs. In view of these results, MRC5 cells, A549 cells, and RD cells should be combined to optimize isolation of HEVs.

  9. A Systematic Review of Outcomes of Contralateral C7 for the Treatment of Traumatic Brachial Plexus Injury: Part 1-Overall outcomes of contralateral C7 transfer for traumatic brachial plexus injury

    PubMed Central

    Yang, Guang; Chang, Kate W.-C.; Chung, Kevin C.

    2015-01-01

    Background Contralateral C7 (CC7) transfer has been used for treating traumatic brachial plexus injury. However, the effectiveness of CC7 transfer remains a subject of debate. We performed a systematic review to study the overall outcomes of CC7 transfer to different recipient nerves in traumatic brachial plexus injuries. Methods A literature search was conducted using PubMed and EMBASE databases to identify original articles related to CC7 transfer for traumatic brachial plexus injury. The data extracted were study/ patient characteristics, and objective outcomes of CC7 transfer to the recipient nerves. We normalized modifications of MRC and other outcome measures into an MRC-based outcome scale for comparisons. Results Thirty-nine studies were identified. The outcomes were categorized based on the three major recipient nerves: median, musculocutaneous, and radial/triceps nerves. Regarding overall functional recovery, 11% of patients achieved MRC grade M4 wrist flexion and 38% achieved M3. Grade M4 finger flexion was achieved by 7% of patients whereas 36% achieved M3. Finally, 56% of patients achieved ≥S3 sensory recovery in the median nerve territories. In the musculocutaneous nerve group, 38% of patients regained elbow flexor strength to M4 and 37% regained to M3. In the radial/triceps nerve group, 25% regained elbow or wrist extension strength to an MRC grade M4 and 25% regained to M3. Conclusions Outcome measures in the included studies were not consistently reported to uncover true patient-related benefits from the CC7 transfer. Reliable and validated outcome instruments should be applied to critically evaluate patients undergoing CC7 transfer. PMID:26397253

  10. Antibody reactivity with Skinner HSV vaccine.

    PubMed

    Muniu, E M; Durham, J; Shariff, D; Hartley, C E; Fuller, A; Melling, J; Wiblin, C; Wilkins, G; Buchan, A; Skinner, G R

    1987-01-01

    Antibody reactivity against herpes simplex virus (HSV) was investigated in 15 subjects who received three subcutaneous immunisations with Skinner HSV vaccine. Humoral antibody responses were detected against type 1 HSV in every subject and against type 2 HSV in all but one subject; immuno-precipitating antibody responses were infrequently detected. There was no antibody reactivity against host-cell (MRC-5), foetal calf serum or rubella virus antigen. None of the vaccinated subjects developed clinical evidence of herpes genitalis.

  11. On the Two-Dimensional Periodic Surface Waves Occurring in Rectangular Vessels: Theory Versus Experiment.

    DTIC Science & Technology

    1985-10-01

    8217.; .:: -,. ".-::", -. ,.-- .i - -,J .- ,il-:l,-,.,,’- , :. 0 MRC Technical summary Report #2878 Thomas J. Bridges University of Wisconsin-Madison 610 Walnut Street D I Madison...without special software. In addition, the analyzer can be programmed to run the experiment and input and analyze the various sensory measurements...PROGRAM ELEMENT. PROJECT. TASK AREA & WORK UNIT NUMBERS *; * ~Mathematics Research Center, University of wr ntNme *610 Walnut Street Wisconsin Physical

  12. Nonlinear Parabolic Equations Involving Measures as Initial Conditions.

    DTIC Science & Technology

    1981-09-01

    CHART N N N Afl4Uf’t 1N II Il MRC Technical Summary Report # 2277 0 NONLINEAR PARABOLIC EQUATIONS INVOLVING MEASURES AS INITIAL CONDITIONS I Haim Brezis ...NONLINEAR PARABOLIC EQUATIONS INVOLVING MEASURES AS INITIAL CONDITIONS Haim Brezis and Avner Friedman Technical Summary Report #2277 September 1981...with NRC, and not with the authors of this report. * 𔃾s ’a * ’ 4| NONLINEAR PARABOLIC EQUATIONS INVOLVING MEASURES AS INITIAL CONDITIONS Haim Brezis

  13. Current Methods for Evaluation of Physical Security System Effectiveness.

    DTIC Science & Technology

    1981-05-01

    Method (Mission Research Corporation ) FSNM Fixed Site Neutralization Model (Vector Research, Inc., for Sandia Laboratories, Albuquerque) PROSE...METHODS a. Security System Performance Assessment Method (SSPAM) (Mission Research Corporation )--The SSPAM concept is an ambitious attempt to carry...Descriptions; Volume III: SSPAM Results; MRC-R-564, Mission Research Corporation , April 1980 Sanderlin, J.C., and Rathman, C.E., A Concept for

  14. Developing Vibrant State Defense Forces: A Successful Medical and Health Service Model

    DTIC Science & Technology

    2006-01-01

    MEDICAL AND HEALTH SERVICE MODEL Colonel (MD) H. Wayne Nelson, Ph.D. Colonel (MD) Robert Barish, M.D. Brigadier General (MD) Frederic Smalkin, J.D...Its Deputy Commander and MRC project action officer was (one of the authors, Nelson), a professor in the Health Science Department in Towson ...Director COL Wayne Nelson, to select “medically-qualified soldiers” who would accept assignment to “participate in humanitarian missions in response and

  15. Memphis Harbor, Mississippi River: Model Investigation

    DTIC Science & Technology

    1950-12-01

    MEMORANDUM NO. 2 -320 CONDUCTED F OR THE PRESIDENT, MISSISSIPPI RIVER COMMISSION ARMY·MRC.VICKSBURG. MISS. CORPS OF ENGINEERS, U. S. ARMY BY...failing to comply with a collection of information if it does not display a currently valid OMB control number 1. REPORT DATE DEC 1950 2 . REPORT TYPE...second wrapper indorsement to Waterways Experiment Station letter dated 2 October 1946, subject: "Proposed Model Study, Presidents Island, Mississippi

  16. 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.

  17. Performance analysis of free space optical system with spatial modulation and diversity combiners over the Gamma Gamma atmospheric turbulence

    NASA Astrophysics Data System (ADS)

    Odeyemi, Kehinde O.; Owolawi, Pius A.; Srivastava, Viranjay M.

    2017-01-01

    Atmospheric turbulence is a major impairment that degrades the performance of free space optical (FSO) communication systems. Spatial modulation (SM) with receive spatial diversity is considered as a powerful technique to mitigate the fading effect induced by atmospheric turbulence. In this paper, the performance of free space optical spatial modulation (FSO-SM) system under Gamma-Gamma atmospheric turbulence is presented. We studied the Average Bit Error Rate (ABER) for the system by employing spatial diversity combiners such Maximum Ratio Combining (MRC) and Equal Gain Combining (EGC) at the receiving end. In particular, we provide a theoretical framework for the system error by deriving Average Pairwise Error Probability (APEP) expression using a generalized infinite power series expansion approach and union bounding technique is applied to obtain the ABER for each combiner. Based on this study, it was found that spatial diversity combiner significantly improved the system error rate where MRC outperforms the EGC. The performance of this system is also compared with other well established diversity combiner systems. The proposed system performance is further improved by convolutional coding technique and our analysis confirmed that the system performance of MRC coded system is enhanced by approximately 20 dB while EGC falls within 17 dB.

  18. Particulate matter (PM) 2.5 levels in ETS emissions of a Marlboro Red cigarette in comparison to the 3R4F reference cigarette under open- and closed-door condition

    PubMed Central

    2012-01-01

    Introduction Potential health damage by environmental emission of tobacco smoke (environmental tobacco smoke, ETS) has been demonstrated convincingly in numerous studies. People, especially children, are still exposed to ETS in the small space of private cars. Although major amounts of toxic compounds from ETS are likely transported into the distal lung via particulate matter (PM), few studies have quantified the amount of PM in ETS. Study aim The aim of this study was to determine the ETS-dependent concentration of PM from both a 3R4F reference cigarette (RC) as well as a Marlboro Red brand cigarette (MRC) in a small enclosed space under different conditions of ventilation to model car exposure. Method In order to create ETS reproducibly, an emitter (ETSE) was constructed and mounted on to an outdoor telephone booth with an inner volume of 1.75 m3. Cigarettes were smoked under open- and closed-door condition to imitate different ventilation scenarios. PM2.5 concentration was quantified by a laser aerosol spectrometer (Grimm; Model 1.109), and data were adjusted for baseline values. Simultaneously indoor and outdoor climate parameters were recorded. The time of smoking was divided into the ETS generation phase (subset “emission”) and a declining phase of PM concentration (subset “elimination”); measurement was terminated after 10 min. For all three time periods the average concentration of PM2.5 (Cmean-PM2.5) and the area under the PM2.5 concentration curve (AUC-PM2.5) was calculated. The maximum concentration (Cmax-PM2.5) was taken from the total interval. Results For both cigarette types open-door ventilation reduced the AUC-PM2.5 (RC: from 59 400 ± 14 600 to 5 550 ± 3 900 μg*sec/m3; MRC: from 86 500 ± 32 000 to 7 300 ± 2 400 μg*sec/m3; p < 0.001) and Cmean-PM2.5 (RC: from 600 ± 150 to 56 ± 40 μg/m3, MRC from 870 ± 320 to 75 ± 25 μg/m3; p < 0.001) by about 90%. Cmax-PM2.5 was reduced by about 80% (RC

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

    PubMed

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

    2010-06-01

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

  20. 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.

  1. Cytotoxicity of Dental Adhesives In Vitro

    PubMed Central

    Koulaouzidou, Elisabeth A.; Helvatjoglu-Antoniades, Maria; Palaghias, George; Karanika-Kouma, Artemis; Antoniades, Dimitrios

    2009-01-01

    Objectives The purpose of this study was to evaluate the cytotoxic effect of six dental adhesives (Admira Bond, Clearfil Liner Bond 2V, ED Primer II, Fuji Bond LC, Gluma Comfort Bond, and NanoBond) applied to cell cultures. Methods The experiments were performed on two cell lines, rat pulp cells (RPC-C2A) and human lung fibroblasts (MRC5). Samples of the adhesives were light-cured and placed in culture medium for 24 hours. The extraction media was applied on the RPC-C2A and the MRC5 cells. Complete medium was used as a control. Cytotoxicity was evaluated with a modified sulforhodamine B (SRB) assay after 24 hours of exposure. Results The cell survival of RPC-C2A cells exposed to Fuji Bond LC, NanoBond, Clearfil Liner Bond 2V, ED Primer II, Admira Bond and Gluma Comfort Bond was 73%, 67%, 50%, 20%, 18% and 5% respectively, relative to the cell survival with the control medium. In the MRC5 cell line, the relative survival was 98%, 80%, 72%, 41%, 19% and 7% after exposure to NanoBond, Fuji Bond LC, Clearfil Liner Bond 2V, ED Primer II, Admira Bond and Gluma Comfort Bond, respectively. Conclusions Different types of dental adhesives showed different cytotoxic effects on cells in vitro. The self-etch adhesives were superior in terms of cytotoxicity. The different cytotoxic effects of dental adhesives should be considered when selecting an appropriate adhesive for operative restorations. PMID:19262725

  2. Cytotoxic constituents of Pachyrhizus tuberosus from Peruvian amazon.

    PubMed

    Leuner, Olga; Havlik, Jaroslav; Budesinsky, Milos; Vrkoslav, Vladimir; Chu, Jessica; Bradshaw, Tracey D; Hummelova, Jana; Miksatkova, Petra; Lapcik, Oldrich; Valterova, Irena; Kokoska, Ladislav

    2013-10-01

    Investigations into the chemical constituents of the seeds of the neglected tuber crop Pachyrhizus tuberosus (Leguminosae) resulted in the isolation of seven components: five rotenoids [12a-hydroxyerosone (1), 12a-hydroxydolineone (2), erosone (3), 12a-hydroxyrotenone (4) and rotenone (6)], a phenylfuranocoumarin [pachyrrhizine (5)] and an isoflavanone [neotenone (7)]. The compounds were isolated using several chromatography techniques and characterized and verified by NMR and HPLC/MS. The MTT assay was used to examine the selective cytotoxic effects of the methanolic P. tuberosus extract and isolated compounds in two human cancer cell lines [breast (MCF-7) and colorectal (HCT-116)] and in non-transformed human fibroblasts (MRC-5); IC50 values were calculated. The methanolic P. tuberosus extract displayed respectable cytotoxic effects against HCT-116 and MCF-7 cells with IC50 values of 7.3 and 6.3 microg/mL, respectively. Of the compounds, 6 exacted greatest cytotoxicity and selectivity towards the cancer cell lines tested, yielding IC50 values of 0.3 microg/mL against both MCF-7 and HCT-116 cells, and a 6-fold reduced activity against MRC-5 fibroblasts. Compound 4 also demonstrated cytotoxicity against MCF-7 and HCT-116 (1.1 and 1.8 microg/mL, respectively), and reduced cytotoxicity towards MRC-5 cells (7.5 mirog/mL). The results revealed from the in vitro cytotoxic MTT assay are worthy of further antitumor investigation.

  3. Dynamic Monitoring of Mechano-Sensing of Cells by Gold Nanoslit Surface Plasmon Resonance Sensor

    PubMed Central

    Wu, Shu-Han; Lee, Kuang-Li; Weng, Ruei-Hung; Zheng, Zhao-Xian; Chiou, Arthur; Wei, Pei-Kuen

    2014-01-01

    We demonstrated a real-time monitoring of live cells upon laminar shear stress stimulation via surface plasmon resonance (SPR) in gold nanoslit array. A large-area gold nanostructure consisted of 500-nm-period nanoslits was fabricated on a plastic film using the thermal-annealed template-stripping method. The SPR in the gold nanoslit array provides high surface sensitivity to monitor cell adhesion changes near the sensor surface. The human non-small cell lung cancer (CL1-0), human lung fibroblast (MRC-5), and human dermal fibroblast (Hs68) were cultured on the gold nanoslits and their dynamic responses to laminar shear stress were measured under different stress magnitudes from 0 to 30 dyne/cm2. Cell adhesion was increased in CL1-0 under shear flow stimulation. No adhesion recovery was observed after stopping the flow. On the other hand, MRC-5 and Hs68 decreased adhesion and recovered from the shear stress. The degree of recovery was around 70% for MRC-5. This device provides dynamic study and early detection of cell adhesion changes under shear flow conditions. PMID:24586846

  4. Detection of Apoptosis and Necrosis in Normal Human Lung Cells Using 1H NMR Spectroscopy

    NASA Astrophysics Data System (ADS)

    Shih, Chwen-Ming; Ko, Wun-Chang; Yang, Liang-Yo; Lin, Chien-Ju; Wu, Jui-Sheng; Lo, Tsui-Yun; Wang, Shwu-Huey; Chen, Chien-Tsu

    2005-05-01

    This study aimed to detect apoptosis and necrosis in MRC-5, a normal human lung cell line, by using noninvasive proton nuclear magnetic resonance (1H NMR). Live MRC-5 cells were processed first for 1H NMR spectroscopy; subsequently their types and the percentage of cell death were assessed on a flow cytometer. Cadmium (Cd) and mercury (Hg) induced apoptosis and necrosis in MRC-5 cells, respectively, as revealed by phosphatidylserine externalization on a flow cytometer. The spectral intensity ratio of methylene (CH2) resonance (at 1.3 ppm) to methyl (CH3) resonance (at 0.9 ppm) was directly proportional to the percentage of apoptosis and strongly and positively correlated with PI staining after Cd treatment (r2 = 0.9868, P < 0.01). In contrast, this ratio only increased slightly within 2-h Hg treatment, and longer Hg exposure failed to produce further increase. Following 2-h Hg exposure, the spectral intensity of choline resonance (at 3.2 ppm) was abolished, but this phenomenon was absent in Cd-induced apoptosis. These findings together demonstrate that 1H NMR is a novel tool with a quantitative potential to distinguish apoptosis from necrosis as early as the onset of cell death in normal human lung cells.

  5. 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

  6. Paraquat increases connective tissue growth factor expression and impairs lung fibroblast proliferation and viscoelasticity.

    PubMed

    Zhang, N; Xie, Y-P; Pang, L; Zang, X-X; Wang, J; Shi, D; Wu, Y; Liu, X-L; Wang, G-H

    2014-12-01

    This in vitro study was designed to investigate the molecular mechanisms of paraquat-induced damage using cultured human fetal lung fibroblasts (MRC-5 cells), in order to promote the development of improved therapies for paraquat poisoning. Paraquat's effects on proliferation were examined by flow cytometry, on viscoelasticity by the micropipette aspiration technique, and on connective tissue growth factor (CTGF) expression by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Paraquat was found to significantly reduce the proliferation index of MRC-5 cells in a concentration-dependent manner (p < 0.05) and to significantly impair the viscoelastic properties in a time-independent manner (p < 0.05). Exposure to paraquat led to a significant and time-dependent increase in CTGF expression (p < 0.05) and induced changes in the morphology and biomechanical characteristics of the MRC-5 cells. These findings not only provide novel insights into the mechanisms of paraquat-induced lung fibrosis but may represent useful targets of improved molecular-based therapies for paraquat poisoning.

  7. Results of ulnar nerve neurotization to biceps brachii muscle in brachial plexus injury

    PubMed Central

    Rezende, Marcelo Rosa De; Rabelo, Neylor Teofilo Araújo; Silveira, Clóvis Castanho; Petersen, Pedro Araújo; Paula, Emygdio José Leomil De; Mattar, Rames

    2012-01-01

    OBJECTIVE: To evaluate the factors influencing the results of ulnar nerve neurotization at the motor branch of the brachii biceps muscle, aiming at the restoration of elbow flexion in patients with brachial plexus injury. METHODS: 19 patients, with 18 men and 1 woman, mean age 28.7 years. Eight patients had injury to roots C5-C6 and 11, to roots C5-C6-C7. The average time interval between injury and surgery was 7.5 months. Four patients had cervical fractures associated with brachial plexus injury. The postoperative follow-up was 15.7 months. RESULTS: Eight patients recovered elbow flexion strength MRC grade 4; two, MRC grade 3 and nine, MRC <3. There was no impairment of the previous ulnar nerve function. CONCLUSION: The surgical results of ulnar nerve neurotization at the motor branch of brachii biceps muscle are dependent on the interval between brachial plexus injury and surgical treatment, the presence of associated fractures of the cervical spine and occipital condyle, residual function of the C8-T1 roots after the injury and the involvement of the C7 root. Signs of reinnervation manifested up to 3 months after surgery showed better results in the long term. Level of Evidence: IV, Case Series. PMID:24453624

  8. 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.

  9. 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.

  10. 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

  11. ROS-mediated cytotoxic effect of copper(II) hydrazone complexes against human glioma cells.

    PubMed

    Recio Despaigne, Angel A; Da Silva, Jeferson G; da Costa, Pryscila R; Dos Santos, Raquel G; Beraldo, Heloisa

    2014-10-27

    2-Acetylpyridine acetylhydrazone (H2AcMe), 2-benzoylpyridine acetylhydrazone (H2BzMe) and complexes [Cu(H2AcMe)Cl2] (1) and [Cu(H2BzMe)Cl2] (2) were assayed for their cytotoxicity against wild type p53 U87 and mutant p53 T98 glioma cells, and against MRC-5 fibroblast cells. Compounds 1 and 2 proved to be more active than the corresponding hydrazones against U87, but not against T98 cells. Compound 1 induced higher levels of ROS than H2AcMe in both glioma cell lines. H2AcMe and 1 induced lower levels of ROS in MRC5 than in U87 cells. Compound 2 induced lower levels of ROS in MRC5 than in T98 cells. The cytotoxic effect of 1 in U87 cells could be related to its ability to provoke the release of ROS, suggesting that the cytotoxicity of 1 might be somehow p53 dependent.

  12. Characterization of Rift Valley fever virus MP-12 strain encoding NSs of Punta Toro virus or sandfly fever Sicilian virus.

    PubMed

    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

  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. Does the MUNIX Method Reflect Clinical Dysfunction in Amyotrophic Lateral Sclerosis: A Practical Experience.

    PubMed

    Gawel, Malgorzata; Kuzma-Kozakiewicz, Magdalena

    2016-05-01

    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 progression in ALS

  15. Dynamic Potential Barrier Effects in Hydrogen Tunneling in Trans-cis Isomerizations

    DTIC Science & Technology

    1993-05-07

    for the cis. As the molecular transla- Schrodinger equation for a molecule to be separated lion and rotation are sepaiated out, the static poten- into...tunneling in multi-dimensional eluding cis and trans conformers of HSiOH. systems semiclassically . However, it is often neces- HSi’ 8OH. HSiOD, and HSi"OD...two equations , liat can he written generally as 1 (r, r. r. (, , V, where rt, 01, and (p, describe the first H-atom. and r., fl, and p2 the second

  16. 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

  17. Improved quality of life in patients with malignant pleural effusion following videoassisted thoracoscopic talc pleurodesis. Preliminary results.

    PubMed

    Basso, Stefano M M; Mazza, Francesco; Marzano, Bernardo; Santeufemia, Davide A; Chiara, Giordano B; Lumachi, Franco

    2012-11-01

    Malignant pleural effusion (MPE) is a common, debilitating complication of several types of advanced malignancy, which may significantly reduce the quality of life of patients. There are several options to treat MPE, including thoracentesis, placement of a long-term indwelling pleural catheter and chemical pleurodesis. The best treatment is still debated, but talc remains the agent of choice to achieve pleurodesis. Forty-six patients (28 men and 18 women; median age 67 years, range 47-82 years) with MPE related to different malignancies underwent video-assisted thoracoscopy talc pleurodesis. There were 26 (56.5%) patients with non-small cell lung cancer, 8 (17.4%) with breast cancer, 7 (15.2%) with pleural mesothelioma and 5 (10.9%) with other malignancies. The average operative time was 28±8 minutes, and the duration of chest tube drainage was 9.4±4.1 days. Side-effects were mild (temporary pain, fever for 2-3 days), affecting only three (12%) patients. Two patients (8%) died during hospitalization, due to progression of disease. Overall, pre- and postoperative Karnofsky performance index (KI) and Medical Research Council (MRC) dyspnea score were 62.1±12.2 vs. 71.3±13.2 (p=0.014), and 4.2±0.8 vs. 2.7±1.0 (p<0.001), respectively. A significant relationship between total amount of preoperative pleural effusion and both KI (R=-0.54, p=0.002) and MRC (R=0.64, p=0.0001) was found. No correlation (p=NS, log-rank test) was found between preoperative KI or MRC and underlying malignancy related to MPE. In conclusion, thoracoscopic large-particle talc pleurodesis is a feasible and effective treatment for MPE, significantly improving quality of life of patients.

  18. Active urea transport independent of H+ and Na+ transport in frog skin epithelium.

    PubMed

    Lacoste, I; Dunel-Erb, S; Harvey, B J; Laurent, P; Ehrenfeld, J

    1991-10-01

    We investigated the relationship between H+ secretion (JH), Na+ absorption (JNa), and urea transport (Ju) in skin of frogs (Rana esculenta) adapted to running tap water, NaCl (100 mM), and KCl (100 mM). In addition, cell morphological changes, particularly in the mitochondria-rich cells (MRC), were followed. NaCl adaptation stimulated an active Ju, reduced JNa and JH, and caused a decrease in the apical surface of MRC. After KCl adaptation, JNa and JH were increased and highly correlated, with a twofold increase in Ju, whereas the numerous MRC developed infoldings on their apical membranes. No correlation was found between JH and Ju. Clamping the skins in a range of +/- 50 mV or changing the external pH from 7.4 to 5.4 (at high cellular buffering power) had no effect on Ju. Depolarization of the basolateral membranes (serosal KCl-Ringer) had no effect on Ju. Ju was reversibly blocked by acidification of the cells by oxygen-free solution and sulfhydryl reagents (Hg2+, p-chloromercuribenzenesulfonic acid, and N-ethylmaleimide). Diethylstilbestrol, a proton transport blocker, had no effect on Ju. Apical addition of amiloride and derivatives (phenamil and ethylisopropyl amiloride) reversibly blocked Ju, whereas ouabain had no effect. We conclude that a cation (Na+ or H+)-dependent process is unlikely to exist in R. esculenta skin. A primary active transport in a two-step process is the simplest hypothesis to account for the energy-dependent Ju that develops in NaCl-adapted frogs.

  19. 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.

  20. 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.

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

    PubMed Central

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

    2005-01-01

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

  2. 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

  3. 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.

  4. 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.

  5. 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.

  6. LGL1 modulates proliferation, apoptosis, and migration of human fetal lung fibroblasts.

    PubMed

    Zhang, Hui; Sweezey, Neil B; Kaplan, Feige

    2015-02-15

    Rapid growth and formation of new gas exchange units (alveogenesis) are hallmarks of the perinatal lung. Bronchopulmonary dysplasia (BPD), common in very premature infants, is characterized by premature arrest of alveogenesis. Mesenchymal cells (fibroblasts) regulate both lung branching and alveogenesis through mesenchymal-epithelial interactions. Temporal or spatial deficiency of late-gestation lung 1/cysteine-rich secretory protein LD2 (LGL1/CRISPLD2), expressed in and secreted by lung fibroblasts, can impair both lung branching and alveogenesis (LGL1 denotes late gestation lung 1 protein; LGL1 denotes the human gene; Lgl1 denotes the mouse/rat gene). Absence of Lgl1 is embryonic lethal. Lgl1 levels are dramatically reduced in oxygen toxicity rat models of BPD, and heterozygous Lgl1(+/-) mice exhibit features resembling human BPD. To explore the role of LGL1 in mesenchymal-epithelial interactions in developing lung, we developed a doxycycline (DOX)-inducible RNA-mediated LGL1 knockdown cellular model in human fetal lung fibroblasts (MRC5(LGL1KD)). We assessed the impact of LGL1 on cell proliferation, cell migration, apoptosis, and wound healing. DOX-induced MRC5(LGL1KD) suppressed cell growth and increased apoptosis of annexin V(+) staining cells and caspase 3/7 activity. LGL1-conditioned medium increased migration of fetal rat primary lung epithelial cells and human airway epithelial cells. Impaired healing by MRC5(LGL1KD) cells of a wound model was attenuated by addition of LGL1-conditioned medium. Suppression of LGL1 was associated with dysregulation of extracellular matrix genes (downregulated MMP1, ColXVα1, and ELASTIN) and proapoptosis genes (upregulated BAD, BAK, CASP2, and TNFRSF1B) and inhibition of 44/42MAPK phosphorylation. Our findings define a role for LGL1 in fibroblast expansion and migration, epithelial cell migration, and mesenchymal-epithelial signaling, key processes in fetal lung development.

  7. Long-term follow-up after bronchoscopic lung volume reduction treatment with coils in patients with severe emphysema

    PubMed Central

    Hartman, Jorine E; Klooster, Karin; Gortzak, Kiki; ten Hacken, Nick HT; Slebos, Dirk-Jan

    2015-01-01

    Background and objective Bronchoscopic lung volume reduction coil (LVR-coil) treatment has been shown to be safe and clinically effective in patients with severe emphysema in the short term; however, long-term safety and effectiveness has not been evaluated. The aim of this study was to investigate the long-term safety and effectiveness of LVR-coil treatment in patients with severe emphysema. Methods Thirty-eight patients with severe emphysema (median age is 59 years, forced expiratory volume in 1 s is 27% predicted) who were treated in LVR-coil clinical trials were invited for a voluntary annual visit. Safety was evaluated by chest X-ray and recording of adverse events and by efficacy by pulmonary function testing, 6-min walk distance (6MWD) and questionnaires. Results Thirty-five patients visited the hospital 1 year, 27 patients 2 years and 22 patients 3 years following coil placement. No coil migrations were observed on X-rays. At 1-year follow-up, all clinical outcomes significantly improved compared with baseline. At 2 years, residual volume % pred, modified Medical Research Council (mMRC) and the SGRQ score were still significantly improved. At 3 years, a significant improvement in mMRC score remained, with 40% of the patients reaching the 6MWD minimal important difference, and 59% for the St George's Respiratory Questionnaire (SGRQ) minimal important difference. Conclusions Follow-up of the patients treated with LVR-coils in our pilot studies showed that the coil treatment is safe with no late pneumothoraces, coil migrations or unexpected adverse events. Clinical benefit gradually declines over time; at 3 years post-treatment, around 50% of the patients maintained improvement in 6MWD, SGRQ and mMRC. PMID:25418910

  8. 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

  9. The predictive value of hierarchical cytogenetic classification in older adults with acute myeloid leukemia (AML): analysis of 1065 patients entered into the United Kingdom Medical Research Council AML11 trial.

    PubMed

    Grimwade, D; Walker, H; Harrison, G; Oliver, F; Chatters, S; Harrison, C J; Wheatley, K; Burnett, A K; Goldstone, A H

    2001-09-01

    Acute myeloid leukemia (AML) in older adults carries a poor prognosis, and the optimum treatment remains to be determined. In younger patients, treatment stratification is frequently based upon diagnostic karyotype, which was the most important prognostic factor in the UK Medical Research Council (MRC) AML10 trial. Considered here is whether karyotype is also predictive in older adults; this is done by studying 1065 cases from MRC AML11 (median age, 66 years). Three prognostic groups were distinguished on the basis of response to induction therapy and overall survival (OS). Those with t(15;17), t(8;21), or inv(16) composed the favorable risk group. Overall, these abnormalities predicted a superior complete remission (CR) rate (72%), reflecting relatively low levels of resistant disease (RD) (8%), and lower relapse risk (RR) (56%) associated with superior OS (34% at 5 years). Normal karyotype (CR, 63%; RD, 17%; RR, 78%; OS, 15%) and other noncomplex abnormalities (CR, 53%; RD, 32%; RR, 85%; OS, 10%) composed the intermediate group; while complex karyotype predicted an extremely poor prognosis (CR, 26%; RD, 56%; RR, 91%; OS, 2%). Combining MRC AML10 and AML11 (n = 2677) revealed that the most favorable changes were rarer in older patients (younger than 55 years, 24%; 55 years or older, 7%), while complex abnormalities were more common (6% vs 13%). This study suggests that hierarchical cytogenetic classification identifies biologically distinct subsets of AML that are represented in all age groups. Furthermore, it highlights the importance of karyotype as a critical independent determinant of outcome in older patients with AML, providing a potential framework for stratified treatment approaches.

  10. Microcirculation alterations in experimentally induced gingivitis in dogs.

    PubMed

    Matsuo, Masato; Okudera, Toshimitsu; Takahashi, Shun-Suke; Wada-Takahashi, Satoko; Maeda, Shingo; Iimura, Akira

    2017-01-01

    The present study aimed to morphologically examine the gingival microvascular network using a microvascular resin cast (MRC) technique, and to investigate how inflammatory disease functionally affects gingival microcirculation using laser Doppler flowmetry (LDF). We used four beagle dogs with healthy periodontal tissue as experimental animals. To cause periodontal inflammation, dental floss was placed around the cervical neck portions of the right premolars. The unmanipulated left premolars served as controls, and received plaque control every 7 days. After 90 days, gingivitis was induced in the experimental side, while the control side maintained healthy gingiva. To perform morphological examinations, we used an MRC method involving the injection of low-viscosity synthetic resin into the blood vessels, leading to peripheral soft-tissue dissolution and permitting observation of the bone, teeth, and vascular cast. Gingival blood flow was estimated using an LDF meter. The control gingival vasculature showed hairpin-loop-like networks along the tooth surface. The blood vessels had diameters of 20-40 μm and were regularly arranged around the cervical portion. On the other hand, the vasculature in the experimental group was twisted and gathered into spiral forms, with blood vessels that had uneven surfaces and smaller diameters of 8-10 μm. LDF revealed reduced gingival blood flow in the group with experimentally induced gingivitis compared to controls. The actual measurements of gingival blood flow by LDF were in agreement with the alterations that would be expected based on the gingivitis-induced morphological alterations observed with the MRC technique.

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

    PubMed Central

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

    2016-01-01

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

  12. 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

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

    NASA Astrophysics Data System (ADS)

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

    2016-10-01

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

  14. Benzo(a)pyrene induces p73 mRNA expression and necrosis in human lung adenocarcinoma H1299 cells.

    PubMed

    Jiang, Ying; Rao, Kaimin; Yang, Guangtao; Chen, Xi; Wang, Qian; Liu, Ailin; Zheng, Hongyan; Yuan, Jing

    2012-03-01

    p53 can mediate DNA damage-induced apoptosis in various cell lines treated with Benzo(a)pyrene (BaP). However, the potential role of p73, one of the p53 family members, in BaP-induced apoptotic cell death remains to be determined. In this study, normal fetal lung fibroblasts (MRC-5) and human lung adenocarcinoma cells (H1299, p53-null) were treated with BaP at concentrations of 8, 16, 32, 64, and 128 μM for 4 and 12 h. The oxidative stress status, extent of DNA damage, expression of p53, p73, mdm2, bcl-2, and bax at the mRNA and protein levels, and the percentages of apoptosis and/or necrosis were assessed. In the two BaP-treated cell lines, we observed increased malondialdehyde (MDA) formation and decreased superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activity at 4 h after the treatment; furthermore, at the time points of 4 and 12 h, we observed extremely high levels of DNA damage. In addition, at 4 h after the treatment, BaP had induced necrosis in MRC-5 and H1299 cells, but it had inhibited apoptosis in MRC-5 cells (P < 0.01 for all). Furthermore, in BaP-treated H1299 cells, only the p73 mRNA level was up-regulated. The results suggested that BaP-induced DNA damage could trigger a shift from apoptotic cell death toward necrotic cell death and that necrotic cell death is independent of p53 and p73 in these cell lines. Future studies are needed to investigate the time course of changes in the type of BaP-induced cell death in more cell lines.

  15. Cephem Potentiation by Inactivation of Nonessential Genes Involved in Cell Wall Biogenesis of β-Lactamase-Producing Escherichia coli.

    PubMed

    Baker, Kristin R; Sigurðardóttir, Helga Høeg; Jana, Bimal; Guardabassi, Luca

    2017-03-01

    Reversal of antimicrobial resistance is an appealing and largely unexplored strategy in drug discovery. The objective of this study was to identify potential targets for "helper" drugs reversing cephem resistance in Escherichia coli strains producing β-lactamases. A CMY-2-encoding plasmid was transferred by conjugation to seven isogenic deletion mutants exhibiting cephem hypersusceptibility. The effect of each mutation was evaluated by comparing the MICs in the wild type and the mutant harboring the same plasmid. Mutation of two genes encoding proteins involved in cell wall biosynthesis, dapF and mrcB, restored susceptibility to cefoxitin (FOX) and reduced the MICs of cefotaxime and ceftazidime, respectively, from the resistant to the intermediate category according to clinical breakpoints. The same mutants harboring a CTX-M-1-encoding plasmid fell into the intermediate or susceptible category for all three drugs. Individual deletion of dapF and mrcB in a clinical isolate of CTX-M-15-producing E. coli sequence type 131 (ST131) resulted in partial reversal of ceftazidime and cefepime resistance but did not reduce MICs below susceptibility breakpoints. Growth curve analysis indicated no fitness cost in a ΔmrcB mutant, whereas a ΔdapF mutant had a 3-fold longer lag phase than the wild type, suggesting that drugs targeting DapF may display antimicrobial activity, in addition to synergizing with selected cephems. DapF appeared to be a potential FOX helper drug target candidate, since dapF inactivation resulted in synergistic potentiation of FOX in the genetic backgrounds tested. The study showed that individual inactivation of two nonessential genes involved in cell wall biogenesis potentiates cephem activity according to drug- and strain-specific patterns.

  16. On Shape Normalization for Non-Uniformly Active Catalyst Pellets. III.

    DTIC Science & Technology

    1981-10-01

    ON SHAPE NORMALIZATION FOR NON-UNIFORMLY ACTIVE CATALYST PELLET--ETC(U) OCT Al M4 MORBIDELLI . A VARMA DAA629 RI C 001 UNCLASSIFIED MRC-TSR-2289 NL 7...RESEARCH CENTRR ON SHAPE NORMALIZATION FOR NON-UNIFORMLY ACTIVE CATALYST PELLETS - III M. Morbidelli and A. Varma Technical Summary Report #2289 October...lies with N4RC, and not with the authors of this report. ON SHAPE NORMALIZATION FOR NON-UNIFORMLY ACTIVE CATALYST PELLETS - III M. Morbidelli and A

  17. Victoria Cowling.

    PubMed

    Cowling, Victoria; Bobrowska, Anna

    2015-08-15

    Victoria Cowling received her BA from the University of Cambridge. She completed her PhD with Julian Downward and Gerard Evan at Cancer Research UK in London, and then moved to the US for a postdoctoral position at Princeton University and Dartmouth College with Michael Cole. Since 2008, she has been running a lab at Dundee University. She is an MRC Senior Research Fellow, a Lister Institute Research Fellow and an EMBO Young Investigator and, in 2015, she was the first recipient of the Women in Cell Biology medal, awarded by the British Society for Cell Biology.

  18. 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.

  19. Folic before frolic.

    PubMed

    Austin, Martine

    2012-10-01

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

  20. EMAGE: a spatial database of gene expression patterns during mouse embryo development.

    PubMed

    Christiansen, Jeffrey H; Yang, Yiya; Venkataraman, Shanmugasundaram; Richardson, Lorna; Stevenson, Peter; Burton, Nicholas; Baldock, Richard A; Davidson, Duncan R

    2006-01-01

    EMAGE (http://genex.hgu.mrc.ac.uk/Emage/database) is a freely available, curated database of gene expression patterns generated by in situ techniques in the developing mouse embryo. It is unique in that it contains standardized spatial representations of the sites of gene expression for each gene, denoted against a set of virtual reference embryo models. As such, the data can be interrogated in a novel and abstract manner by using space to define a query. Accompanying the spatial representations of gene expression patterns are text descriptions of the sites of expression, which also allows searching of the data by more conventional text-based methods.

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

    SciTech Connect

    Thomas, I.

    1995-10-01

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

  2. 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.

  3. 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.

  4. Sensitivity Assessment of Ozone Models

    SciTech Connect

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

    2000-01-24

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

  5. Pharmacomodulation on the 3-acetylursolic acid skeleton: Design, synthesis, and biological evaluation of novel N-{3-[4-(3-aminopropyl)piperazinyl]propyl}-3-O-acetylursolamide derivatives as antimalarial agents.

    PubMed

    Gnoatto, Simone C B; Susplugas, Sophie; Dalla Vechia, Luciana; Ferreira, Thais B; Dassonville-Klimpt, Alexandra; Zimmer, Karine R; Demailly, Catherine; Da Nascimento, Sophie; Guillon, Jean; Grellier, Philippe; Verli, Hugo; Gosmann, Grace; Sonnet, Pascal

    2008-01-15

    A series of new piperazine derivatives of ursolic acid was synthesized and tested against Plasmodium falciparum strains. They were also tested on their cytotoxicity effects upon MRC-5 cells. Seven new piperazinyl analogues showed significant activity in the nanomolar range (IC(50)=78-167nM) against Plasmodium falciparum CQ-resistant strain FcB1. A possible mechanism of interaction implicating binding of these compounds to beta-hematin was supported by in vitro tests. Moreover, the importance of the hydrophilic framework attached at the terminal nitrogen atom of the bis-(3-aminopropyl)piperazine joined to the triterpene ring was also explored through molecular dynamic simulations.

  6. Convergence of Cubic Spline Interpolation with the Not-A-Knot Condition.

    DTIC Science & Technology

    1985-10-01

    TEST CHART NATIONA, 61ORFAL OF STANC’ARP 1%, A -R ,. i • , e o " C) MRC Technical Summary...Report #2876 i’ ’- CONVERGFNCI- OF CUBIC SPUINF INTERP()LATIONWI-T! TH..- -N)T-A-KNOT CONDITION ,’,-’.... q Carl d,, f,<, .i ’oi.’ - M." s . W-.ns-530...October 3, 1985) S -’"-B’Ŕ OliC ILE COPApproved for public release r’ QI~ rL OYDistribution unlimited." ...i-i’" . Sponsored by".-.’’- IJ. S . Army

  7. Rheum emodin inhibits enterovirus 71 viral replication and affects the host cell cycle environment

    PubMed Central

    Zhong, Ting; Zhang, Li-ying; Wang, Zeng-yan; Wang, Yue; Song, Feng-mei; Zhang, Ya-hong; Yu, Jing-hua

    2017-01-01

    Human enterovirus 71 (EV71) is the primary causative agent of recent large-scale outbreaks of hand, foot, and mouth disease (HFMD) in Asia. Currently, there are no drugs available for the prevention and treatment of HFMD. In this study, we compared the anti-EV71 activities of three natural compounds, rheum emodin, artemisinin and astragaloside extracted from Chinese herbs Chinese rhubarb, Artemisia carvifolia and Astragalus, respectively, which have been traditionally used for the treatment and prevention of epidemic diseases. Human lung fibroblast cell line MRC5 was mock-infected or infected with EV71, and treated with drugs. The cytotoxicity of the drugs was detected with MTT assay. The cytopathic effects such as cell death and condensed nuclei were morphologically observed. The VP1-coding sequence required for EV71 genome replication was assayed with qRT-PCR. Viral protein expression was analyzed with Western blotting. Viral TCID50 was determined to evaluate EV71 virulence. Flow cytometry analysis of propidium iodide staining was performed to analyze the cell cycle distribution of MRC5 cells. Rheum emodin (29.6 μmol/L) effectively protected MRC5 cells from EV71-induced cytopathic effects, which resulted from the inhibiting viral replication: rheum emodin treatment decreased viral genomic levels by 5.34-fold, viral protein expression by less than 30-fold and EV71 virulence by 0.33107-fold. The fact that inhibition of rheum emodin on viral virulence was much stronger than its effects on genomic levels and viral protein expression suggested that rheum emodin inhibited viral maturation. Furthermore, rheum emodin treatment markedly diminished cell cycle arrest at S phase in MRC5 cells, which was induced by EV71 infection and favored the viral replication. In contrast, neither astragaloside (50 μmol/L) nor artemisinin (50 μmol/L) showed similar anti-EV71 activities. Among the three natural compounds tested, rheum emodin effectively suppressed EV71 viral replication

  8. 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

  9. 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

  10. Decision Support for Attack Submarine Commanders.

    DTIC Science & Technology

    1980-10-01

    AD-AO95 892 DECISION SCIENCE CONSORTIUM INC FALLS CHURCH VA F./e 12/2 DECISION SUPPORT FOR ATTACK SUBMARINE COMMANDERS. (U) OCT 80 M S COHEN, R V...BROWN N00014-80-C-0046 UNCLASSIFIED TR-8S-11 ML DECISIN IEN$CE CUIVSURTiUM, MrC. DECISION SUPPORT FOR A TTA CK SUBMARINE COMMANDERS Marvin S . Cohen and...on reverse) DDI ,o..ŕ 1473 EDITION OF I NOV 65 IS OISOLCTZ Unclassified S /N 0102-014-6601 1 SECURITY CLASIFICATION OF TNIS PAGE (10bon DW& tateo* 01

  11. Inverse lithography technology (ILT): a natural solution for model-based SRAF at 45-nm and 32-nm

    NASA Astrophysics Data System (ADS)

    Pang, Linyong; Liu, Yong; Abrams, Dan

    2007-05-01

    In this paper, we present the Luminescent's ILT approach that can rapidly solve for the optimal photomask design. We will discuss the latest development of ILT at Luminescent in the areas of sub-resolution assist feature (SRAF) generation, process-window-based ILT and mask rule compliance (MRC). Results collected internally and from customers demonstrate that ILT is not only an R&D tool, but also a tool quickly maturing for production qualification at advanced technology nodes. By enforcing the proper constraints while optimizing the masks, ILT can improve process windows while maintaining mask costs at a reasonable level.

  12. 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

  13. Women's choices for fetal chromosome analysis.

    PubMed

    Abramsky, L; Rodeck, C H

    1991-01-01

    Five hundred and eighty women aged 35 or more at the expected date of delivery were offered the chance to join the MRC trial comparing CVS and amniocentesis at Queen Charlotte's Hospital. After a 1 h non-directive counselling session, they were asked to choose between having no test, having amniocentesis, or joining the trial in the hopes of having CVS (or in some cases having CVS outside the trial). The majority of women chose to have some test, and CVS was a more popular choice than amniocentesis.

  14. A Review of Depleted Uranium Biological Effects: In Vitro Studies (Briefing charts)

    DTIC Science & Technology

    2010-11-01

    MeV, 5 cGy) Short-Term Carcinogenicity Tests In Vitro: Relative Comparison of DU, Nickel, and Alpha Particles Miller, et al, Environmental Health... Tested (20) Uranium Isotopes: Rad Activity Chem Tox DU 0.43 1.0 238U 0.33 1.0 Special thanks to Gwen Watson, MRC UK Alpha Particle Genomic Instability...Micronuclei as Endpoint of Genomic Instability Due to Radiation Effect Number of Clones Tested (5-7) Number of Clones Tested (20) Uranium Isotopes: Rad

  15. Relationship between Breathlessness and Anxiety in Asthma and Bronchitis: A Comparative Study

    PubMed Central

    Oswald, N. C.; Waller, R. E.; Drinkwater, J.

    1970-01-01

    Two personality testing forms, the Eysenck Personality Inventory Form A and the Cattell Self Analysis Form, were completed on 471 hospital patients who fell within the general diagnostic range of asthma, bronchitis, or both. Respiratory diagnoses were based on the standard M.R.C. questionary. All categories of patients showed a tendency towards neuroticism, anxiety, and introversion, and the scores were slightly higher for bronchitics than for asthmatics. Neuroticism and anxiety increased with increasing respiratory disability. Variations in these scores with age of onset of symptoms and length of history were small. PMID:5440566

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

    PubMed

    Martin, Aryn

    2007-09-01

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

  17. Differentiation syndrome in acute myeloid leukemia after treatment with azacitidine.

    PubMed

    Laufer, Christin B; Roberts, Owen

    2015-11-01

    We report a case report of hyperleukocytosis, fever, hypotension, pulmonary and pericardial effusions, and acute kidney injury during initial treatment with azacitidine in a patient with AML-MRC. Collectively, the symptomatology resembled differentiation syndrome. Azacitidine has been previously associated with fever, peripheral edema, and hyperleukocytosis, but its side effect profile has never been described as similar to differentiation syndrome. The patient's deteriorating course quickly turned around after treatment with dexamethasone. This potential reaction, and potential treatment, is important for clinicians to be aware of.

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

    NASA Astrophysics Data System (ADS)

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

    2015-09-01

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

  19. Erectile dysfunction in COPD patients.

    PubMed

    Turan, Onur; Ure, Iyimser; Turan, Pakize Ayse

    2016-02-01

    Sexual dysfunction is a common problem in chronic obstructive pulmonary disease (COPD). We aimed to assess the presence of erectile dysfunction (ED) in COPD patients. Ninety-three outpatients who had been diagnosed as COPD and followed in Bolvadin State Hospital, Afyon, Turkey, were included in the study. All patients underwent pulmonary function tests and arterial blood gas analysis. They completed International Physical Activity Questionnaire (IPAQ), Medical Research Council (MRC) Dyspnea Scale, Short Form 36-item Scale (SF-36), and International Index of Erectile Function (IIEF) Questionnaire. The mean age of 10 (10.8%) mild, 46 (49.5%) moderate, 28 (30.1%) severe, and 9 (9.7%) very severe COPD patients was 61.4 ± 9.8 years. Varying degrees of ED were detected in 67.7% of COPD patients. All patients with hypoxemia had ED. IPAQ score and all SF-36 parameters were low in patients with ED, while MRC score was high. Forced expiratory volume in one second, forced vital capacity, partial pressure of oxygen in blood, oxygen (O2) saturation, IPAQ score, and role-physical parameters were statistically low in ED patients (p = 0.04, 0.02, <0.01, <0.01, 0.02, and 0.04, respectively); MRC score was statistically higher in patients with ED (p = 0.02). Patients with moderate and severe ED had statistically lower score of mental health (p < 0.01 and p = 0.02, respectively). There was a positive correlation between IIEF score and IPAQ scores (p < 0.01), MRC scores (p = 0.01), general health (p < 0.01), role-physical (p < 0.01), role-emotional (p < 0.01), physical functioning (p < 0.01), and mental health (p < 0.01) parameters in SF-36. ED is frequently seen in COPD patients. Hypoxemia, smoking, and limitation of physical activity are thought to be associated with ED in COPD as mechanisms. Quality of life and the functional capacity are negatively affected with the presence of ED. It is important for a physician to question the sexual functions in patients with COPD. The

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

    PubMed

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

    2013-01-01

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

  1. The Control of Orbital Mixing in Ruthenium Complexes Containing Quinone Related Ligands

    DTIC Science & Technology

    1991-04-04

    F D’rN MiTcr) F1 S.-’-’ -5 i"’C .1sktuInii 2a A EOP 5 EP0N6 ic %-𔃻,10AL ’ -:- 0 1 IoilouoC Area coce) 22C ;"C;- 3yMBOL Dr Roald A.De Mrc 110 FORM...Liaw, D.-S.; Chen, CA-.; Wang , Y. Inorg. China. Acta 1985, Ji(3, L31.. 28. Christoph, G. G.; Goedken, V. L. J. Am. Chem. Soc. 1973, 25, 3869. 29. Hall

  2. Antiproliferative Withanolides from Datura wrightii#

    PubMed Central

    Zhang, Huaping; Bazzill, Joseph; Gallagher, Robert J.; Subramanian, Chitra; Grogan, Patrick T.; Day, Victor W.; Kindscher, Kelly; Cohen, Mark S.; Timmermann, Barbara N.

    2013-01-01

    A new withanolide (1) named withawrightolide, and four known withanolides (2–5) were isolated from the aerial parts of Datura wrightii (Solanaceae). The structure of compound 1 was elucidated through 2D NMR and other spectroscopic techniques. In addition, the structure of withametelin L (2) was confirmed by X-ray crystallographic analysis. Using MTS viability assays, withanolides 1–5 showed antiproliferative activities against human glioblastoma (U251 and U87), head and neck squamous cell carcinoma (MDA-1986), and normal fetal lung fibroblast (MRC-5) cells with IC50 values in the range between 0.56 and 5.6 μM. PMID:23252848

  3. Identification of cell lines permissive for human coronavirus NL63.

    PubMed

    Schildgen, Oliver; Jebbink, Maarten F; de Vries, Michel; Pyrc, Krzysztov; Dijkman, Ronald; Simon, Arne; Müller, Andreas; Kupfer, Bernd; van der Hoek, Lia

    2006-12-01

    Six cell lines routinely used in laboratories were tested for permissiveness to the infection with the newly identified human coronavirus NL63. Two monkey epithelial cell lines, LLC-MK2 and Vero-B4, showed a cytopathic effect (CPE) and clear viral replication, whereas no CPE or replication was observed in human lung fibroblasts MRC-5s. In Rhabdomyosarcoma cells, Madin-Darby-Canine-kidney cells and in an undefined monkey kidney cell line some replication was observed but massive exponential rise in virus yield lacked The results will lead to an improved routine diagnostic algorithm for the detection of the human coronavirus NL63.

  4. Rheum emodin inhibits enterovirus 71 viral replication and affects the host cell cycle environment.

    PubMed

    Zhong, Ting; Zhang, Li-Ying; Wang, Zeng-Yan; Wang, Yue; Song, Feng-Mei; Zhang, Ya-Hong; Yu, Jing-Hua

    2017-03-01

    Human enterovirus 71 (EV71) is the primary causative agent of recent large-scale outbreaks of hand, foot, and mouth disease (HFMD) in Asia. Currently, there are no drugs available for the prevention and treatment of HFMD. In this study, we compared the anti-EV71 activities of three natural compounds, rheum emodin, artemisinin and astragaloside extracted from Chinese herbs Chinese rhubarb, Artemisia carvifolia and Astragalus, respectively, which have been traditionally used for the treatment and prevention of epidemic diseases. Human lung fibroblast cell line MRC5 was mock-infected or infected with EV71, and treated with drugs. The cytotoxicity of the drugs was detected with MTT assay. The cytopathic effects such as cell death and condensed nuclei were morphologically observed. The VP1-coding sequence required for EV71 genome replication was assayed with qRT-PCR. Viral protein expression was analyzed with Western blotting. Viral TCID50 was determined to evaluate EV71 virulence. Flow cytometry analysis of propidium iodide staining was performed to analyze the cell cycle distribution of MRC5 cells. Rheum emodin (29.6 μmol/L) effectively protected MRC5 cells from EV71-induced cytopathic effects, which resulted from the inhibiting viral replication: rheum emodin treatment decreased viral genomic levels by 5.34-fold, viral protein expression by less than 30-fold and EV71 virulence by 0.33107-fold. The fact that inhibition of rheum emodin on viral virulence was much stronger than its effects on genomic levels and viral protein expression suggested that rheum emodin inhibited viral maturation. Furthermore, rheum emodin treatment markedly diminished cell cycle arrest at S phase in MRC5 cells, which was induced by EV71 infection and favored the viral replication. In contrast, neither astragaloside (50 μmol/L) nor artemisinin (50 μmol/L) showed similar anti-EV71 activities. Among the three natural compounds tested, rheum emodin effectively suppressed EV71 viral replication

  5. Assessment of packed bed bioreactor systems in the production of viral vaccines

    PubMed Central

    2014-01-01

    Vaccination is believed to be the most effective method for the prevention of infectious diseases. Thus it is imperative to develop cost effective and scalable process for the production of vaccines so as to make them affordable for mass use. In this study, performance of a novel disposable iCELLis fixed bed bioreactor system was investigated for the production of some viral vaccines like Rabies, Hepatitis-A and Chikungunya vaccines in comparison to conventional systems like the commercially available packed bed system and roller bottle system. Vero and MRC-5 cell substrates were evaluated for growth parameters in all the three systems maintaining similar seeding density, multiplicity of infection (MOI) and media components. It was observed that Vero cells showed similar growth in all the three bioreactors whereas MRC-5 cells showed better growth in iCELLis Nano system and roller bottle system. Subsequently, the virus infection and antigen production studies also revealed that for Hepatitis-A and Chikungunya iCELLis Nano bioreactor system was better to the commercial packed bed bioreactor and roller bottle systems. Although for rabies antigen production commercially available packed bed bioreactor system was found to be better. This study shows that different bioreactor platforms may be employed for viral vaccine production and iCELLis Nano is one of such new convenient and a stable platform for production of human viral vaccines. PMID:24949260

  6. Assessment of packed bed bioreactor systems in the production of viral vaccines.

    PubMed

    Rajendran, Ramya; Lingala, Rajendra; Vuppu, Siva Kumar; Bandi, Bala Obulapathi; Manickam, Elaiyaraja; Macherla, Sankar Rao; Dubois, Stéphanie; Havelange, Nicolas; Maithal, Kapil

    2014-01-01

    Vaccination is believed to be the most effective method for the prevention of infectious diseases. Thus it is imperative to develop cost effective and scalable process for the production of vaccines so as to make them affordable for mass use. In this study, performance of a novel disposable iCELLis fixed bed bioreactor system was investigated for the production of some viral vaccines like Rabies, Hepatitis-A and Chikungunya vaccines in comparison to conventional systems like the commercially available packed bed system and roller bottle system. Vero and MRC-5 cell substrates were evaluated for growth parameters in all the three systems maintaining similar seeding density, multiplicity of infection (MOI) and media components. It was observed that Vero cells showed similar growth in all the three bioreactors whereas MRC-5 cells showed better growth in iCELLis Nano system and roller bottle system. Subsequently, the virus infection and antigen production studies also revealed that for Hepatitis-A and Chikungunya iCELLis Nano bioreactor system was better to the commercial packed bed bioreactor and roller bottle systems. Although for rabies antigen production commercially available packed bed bioreactor system was found to be better. This study shows that different bioreactor platforms may be employed for viral vaccine production and iCELLis Nano is one of such new convenient and a stable platform for production of human viral vaccines.

  7. Pixel-based OPC optimization based on conjugate gradients.

    PubMed

    Ma, Xu; Arce, Gonzalo R

    2011-01-31

    Optical proximity correction (OPC) methods are resolution enhancement techniques (RET) used extensively in the semiconductor industry to improve the resolution and pattern fidelity of optical lithography. In pixel-based OPC (PBOPC), the mask is divided into small pixels, each of which is modified during the optimization process. Two critical issues in PBOPC are the required computational complexity of the optimization process, and the manufacturability of the optimized mask. Most current OPC optimization methods apply the steepest descent (SD) algorithm to improve image fidelity augmented by regularization penalties to reduce the complexity of the mask. Although simple to implement, the SD algorithm converges slowly. The existing regularization penalties, however, fall short in meeting the mask rule check (MRC) requirements often used in semiconductor manufacturing. This paper focuses on developing OPC optimization algorithms based on the conjugate gradient (CG) method which exhibits much faster convergence than the SD algorithm. The imaging formation process is represented by the Fourier series expansion model which approximates the partially coherent system as a sum of coherent systems. In order to obtain more desirable manufacturability properties of the mask pattern, a MRC penalty is proposed to enlarge the linear size of the sub-resolution assistant features (SRAFs), as well as the distances between the SRAFs and the main body of the mask. Finally, a projection method is developed to further reduce the complexity of the optimized mask pattern.

  8. MiR-21 is involved in radiation-induced bystander effects.

    PubMed

    Xu, Shuai; Ding, Nan; Pei, Hailong; Hu, Wentao; Wei, Wenjun; Zhang, Xurui; Zhou, Guangming; Wang, Jufang

    2014-01-01

    Radiation-induced bystander effects are well-established phenomena, in which DNA damage responses are induced not only in the directly irradiated cells but also in the non-irradiated bystander cells through intercellular signal transmission. Recent studies hint that bystander effects are possibly mediated via small non-coding RNAs, especially microRNAs. Thus, more details about the roles of microRNA in bystander effects are urgently needed to be elucidated. Here we demonstrated that bystander effects were induced in human fetal lung MRC-5 fibroblasts through medium-mediated way by different types of radiation. We identified a set of differentially expressed microRNAs in the cell culture medium after irradiation, among which the up-regulation of miR-21 was further verified with qRT-PCR. In addition, we found significant upregulation of miR-21 in both directly irradiated cells and bystander cells, which was confirmed by the expression of miR-21 precursor and its target genes. Transfection of miR-21 mimics into non-irradiated MRC-5 cells caused bystander-like effects. Taken together, our data reveals that miR-21 is involved in radiation-induced bystander effects. Elucidation of such a miRNA-mediated bystander effect is of utmost importance in understanding the biological processes related to ionizing radiation and cell-to-cell communication.

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

    NASA Technical Reports Server (NTRS)

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

    1992-01-01

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

  10. Histiocytoid cardiomyopathy and microphthalmia with linear skin defects syndrome: phenotypes linked by truncating variants in NDUFB11

    PubMed Central

    Rea, Gillian; Homfray, Tessa; Till, Jan; Roses-Noguer, Ferran; Buchan, Rachel J.; Wilkinson, Sam; Wilk, Alicja; Walsh, Roddy; John, Shibu; McKee, Shane; Stewart, Fiona J.; Murday, Victoria; Taylor, Robert W.; Ashworth, Michael; Baksi, A. John; Daubeney, Piers; Prasad, Sanjay; Barton, Paul J.R.; Cook, Stuart A.; Ware, James S.

    2017-01-01

    Variants in NDUFB11, which encodes a structural component of complex I of the mitochondrial respiratory chain (MRC), were recently independently reported to cause histiocytoid cardiomyopathy (histiocytoid CM) and microphthalmia with linear skin defects syndrome (MLS syndrome). Here we report an additional case of histiocytoid CM, which carries a de novo nonsense variant in NDUFB11 (ENST00000276062.8: c.262C > T; p.[Arg88*]) identified using whole-exome sequencing (WES) of a family trio. An identical variant has been previously reported in association with MLS syndrome. The case we describe here lacked the diagnostic features of MLS syndrome, but a detailed clinical comparison of the two cases revealed significant phenotypic overlap. Heterozygous variants in HCCS (which encodes an important mitochondrially targeted protein) and COX7B, which, like NDUFB11, encodes a protein of the MRC, have also previously been identified in MLS syndrome including a case with features of both MLS syndrome and histiocytoid CM. However, a systematic review of WES data from previously published histiocytoid CM cases, alongside four additional cases presented here for the first time, did not identify any variants in these genes. We conclude that NDUFB11 variants play a role in the pathogenesis of both histiocytoid CM and MLS and that these disorders are allelic (genetically related). PMID:28050600

  11. [Effects of organic-inorganic mixed fertilizers on rice yield and nitrogen use efficiency].

    PubMed

    Zhang, Xiao-li; Meng, Lin; Wang, Qiu-jun; Luo, Jia; Huang, Qi-wei; Xu, Yang-chun; Yang, Xing-ming; Shen, Qi-rong

    2009-03-01

    A field experiment was carried to study the effects of organic-inorganic mixed fertilizers on rice yield, nitrogen (N) use efficiency, soil N supply, and soil microbial diversity. Rapeseed cake compost (RCC), pig manure compost (PMC), and Chinese medicine residue compost (MRC) were mixed with chemical N, P and K fertilizers. All the treatments except CK received the same rate of N. The results showed that all N fertilizer application treatments had higher rice yield (7918.8-9449.2 kg x hm(-2)) than the control (6947.9 kg x hm(-2)). Compared with that of chemical fertilizers (CF) treatment (7918.8 kg x hm(-2)), the yield of the three organic-inorganic mixed fertilizers treatments ranged in 8532.0-9449.2 kg x hm(-2), and the increment was 7.7%-19.3%. Compared with treatment CF, the treatments of organic-inorganic mixed fertilizers were significantly higher in N accumulation, N transportation efficiency, N recovery rate, agronomic N use efficiency, and physiological N use efficiency. These mixed fertilizers treatments promoted rice N uptake and improved soil N supply, and thus, increased N use efficiency, compared with treatments CF and CK. Neighbor joining analysis indicated that soil bacterial communities in the five treatments could be classified into three categories, i.e., CF and CK, PMC and MRC, and RCC, implying that the application of exogenous organic materials could affect soil bacterial communities, while applying chemical fertilizers had little effect on them.

  12. Comparing curvilinear vs Manhattan ILT shape efficacy on EPE and process window

    NASA Astrophysics Data System (ADS)

    Zhang, Dan; Buck, Peter; Tritchkov, Alexander; Madhusudhan, Saikiran; Word, James

    2016-10-01

    Inverse Lithography Technology (ILT) is gaining acceptance as part of a comprehensive OPC solution especially as a repair technique to locally improve process window where conventional OPC does not have enough degrees of freedom to produce acceptable results. [1] Since ILT is significantly more computationally intensive than conventional OPC, a localized application of ILT does not significantly increase OPC cycle time. As ILT methods mature and become more efficient, combined with the availability of huge compute clusters for post tape out data processing, the possibility of full-field ILT OPC could soon become reality. Full-field ILT OPC may provide improved process window and greater layout flexibility as long as multi-patterning methods with 193 nm exposure wavelength remain the primary lithography strategy for advanced technology nodes. Due to limitations of photomask lithography tools that prevent efficient exposure of non-Manhattan shapes, ILT OPC output is typically post-processed to conform to mask MRC rules, rendering the raw all-angle features to a Manhattanized equivalent. Previous comparisons of raw vs Manhattan ILT OPC at earlier nodes have shown that a Manhattanized output can be made to print on wafer with equivalent process window while conforming to mask manufacturing rules.[2,3,4] In this paper we use wafer-level lithography simulation to compare raw vs Manhattanized ILT output based on current advanced nodes and MRC rules. We expand this study to include a mask model to ensure that mask corner rounding effects are considered.

  13. De novo AML exhibits greater microenvironment dysregulation compared to AML with myelodysplasia-related changes.

    PubMed

    Lopes, Matheus Rodrigues; Pereira, João Kleber Novais; de Melo Campos, Paula; Machado-Neto, João Agostinho; Traina, Fabiola; Saad, Sara T Olalla; Favaro, Patricia

    2017-01-13

    The interaction between the bone marrow microenvironment and malignant hematopoietic cells can result in the protection of leukemia cells from chemotherapy in both myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We, herein, characterized the changes in cytokine expression and the function of mesenchymal stromal cells (MSC) in patients with MDS, AML with myelodysplasia-related changes (MRC), a well-recognized clinical subtype of secondary AML, and de novo AML. We observed a significant inhibitory effect of MDS-MSC on T lymphocyte proliferation and no significant differences in any of the cytokines tested. AML-MSC inhibited T-cell proliferation only at a very low MSC/T cell ratio. When compared to the control, AML-MRCderived MSC presented a significant increase in IL6 expression, whereas de novo AML MSC presented a significant increase in the expression levels of VEGFA, CXCL12, RPGE2, IDO, IL1β, IL6 and IL32, followed by a decrease in IL10 expression. Furthermore, data indicate that IL-32 regulates stromal cell proliferation, has a chemotactic potential and participates in stromal cell crosstalk with leukemia cells, which could result in chemoresistance. Our results suggest that the differences between AML-MRC and de novo AML also extend into the leukemic stem cell niche and that IL-32 can participate in the regulation of the bone marrow cytokine milieu.

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

    PubMed

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

    1996-09-01

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

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

    PubMed Central

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

    2015-01-01

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

  16. Endogenous prostaglandin E2 potentiates anti-inflammatory phenotype of macrophage through the CREB-C/EBP-β cascade.

    PubMed

    Na, Yi Rang; Jung, Daun; Yoon, Bo Ruem; Lee, Won Woo; Seok, Seung Hyeok

    2015-09-01

    Macrophages have important functions in tissue homeostasis, but the exact mechanisms regarding wide spectrum of macrophage phenotype remain unresolved. In this study, we report that mouse bone marrow derived naïve macrophages produce prostaglandin E2 (PGE2 ) endogenously, resulting in anti-inflammatory gene expression upon differentiation induced by macrophage colony stimulating factor (M-CSF). Cyclooxygenase (COX) inhibition by indomethacin reduced endogenous PGE2 production of macrophages and subsequently reduced arg1, IL10 and Mrc1, YmI and FizzI gene expressions. Of note, PGE2 phosphorylates CREB via EP2 and EP4 receptor ligation, thereby transcriptionally increasing C/EBP-β expression in BALB/c bone marrow derived macrophages. Activated CREB directly binds to the CREB-responsive element of the C/EBP-β promoter, such that PGE2 ultimately reinforces arg1, IL10 and Mrc1 gene expression. Cyclic AMP activator forskolin also phosphorylated CREB and induced the C/EBP-β cascade, but this was completely blocked by the PKA inhibitor, H89. Consequently, M-CSF grown macrophages inhibited T-cell proliferation but the inhibition ability was reduced when the COX is inhibited by indomethacin or macrophage C/EBP-β expression was decreased by siRNA transduction. Our results collectively describe the molecular basis for homeostatic macrophage differentiation by endogenous PGE2 .

  17. Impact and Mitigation of Multiantenna Analog Front-End Mismatch in Transmit Maximum Ratio Combining

    NASA Astrophysics Data System (ADS)

    Liu, Jian; Khaled, Nadia; Petré, Frederik; Bourdoux, André; Barel, Alain

    2006-12-01

    Transmit maximum ratio combining (MRC) allows to extend the range of wireless local area networks (WLANs) by exploiting spatial diversity and array gains. These gains, however, depend on the availability of the channel state information (CSI). In this perspective, an open-loop approach in time-division-duplex (TDD) systems relies on channel reciprocity between up- and downlink to acquire the CSI. Although the propagation channel can be assumed to be reciprocal, the radio-frequency (RF) transceivers may exhibit amplitude and phase mismatches between the up- and downlink. In this contribution, we present a statistical analysis to assess the impact of these mismatches on the performance of transmit-MRC. Furthermore, we propose a novel mixed-signal calibration scheme to mitigate these mismatches, which allows to reduce the implementation loss to as little as a few tenths of a dB. Finally, we also demonstrate the feasibility of the proposed calibration scheme in a real-time wireless MIMO-OFDM prototyping platform.

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

    PubMed Central

    Leeming-Latham, Clare

    2015-01-01

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

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

    PubMed Central

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

    2016-01-01

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

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

    NASA Astrophysics Data System (ADS)

    Thu, Hang Ngo; Wehn, Uta

    2016-05-01

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

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

    PubMed

    Bhatt, Arun

    2010-01-01

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

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

    PubMed

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

    2015-02-01

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

  3. Evaluation of sustained release polylactate electron donors for removal of hexavalent chromium from contaminated groundwater

    SciTech Connect

    Brodie, E.L.; Joyner, D. C.; Faybishenko, B.; Conrad, M. E.; Rios-Velazquez, C.; Mork, B.; Willet, A.; Koenigsberg, S.; Herman, D.; Firestone, M. K.; Hazen, T. C.; Malave, Josue; Martinez, Ramon

    2011-02-15

    To evaluate the efficacy of bioimmobilization of Cr(VI) in groundwater at the Department of Energy Hanford site, we conducted a series of microcosm experiments using a range of commercial electron donors with varying degrees of lactate polymerization (polylactate). These experiments were conducted using Hanford Formation sediments (coarse sand and gravel) immersed in Hanford groundwater, which were amended with Cr(VI) and several types of lactate-based electron donors (Hydrogen Release Compound, HRC; primer-HRC, pHRC; extended release HRC) and the polylactate-cysteine form (Metal Remediation Compound, MRC). The results showed that polylactate compounds stimulated an increase in bacterial biomass and activity to a greater extent than sodium lactate when applied at equivalent carbon concentrations. At the same time, concentrations of headspace hydrogen and methane increased and correlated with changes in the microbial community structure. Enrichment of Pseudomonas spp. occurred with all lactate additions, and enrichment of sulfate-reducing Desulfosporosinus spp. occurred with almost complete sulfate reduction. The results of these experiments demonstrate that amendment with the pHRC and MRC forms result in effective removal of Cr(VI) from solution most likely by both direct (enzymatic) and indirect (microbially generated reductant) mechanisms.

  4. One-step electrochemical deposition of Schiff base cobalt complex as effective water oxidation catalyst

    NASA Astrophysics Data System (ADS)

    Huang, Binbin; Wang, Yan; Zhan, Shuzhong; Ye, Jianshan

    2017-02-01

    Schiff base metal complexes have been applied in many fields, especially, a potential homogeneous catalyst for water splitting. However, the high overpotential, time consumed synthesis process and complicated working condition largely limit their application. In the present work, a one-step approach to fabricate Schiff base cobalt complex modified electrode is developed. Microrod clusters (MRC) and rough spherical particles (RSP) can be obtained on the ITO electrode through different electrochemical deposition condition. Both of the MRC and RSP present favorable activity for oxygen evolution reaction (OER) compared to the commercial Co3O4, taking an overpotential of 650 mV and 450 mV to drive appreciable catalytic current respectively. The highly active and stable RSP shows a Tafel plot of 84 mV dec-1 and negligible decrease of the current density for 12 h bulk electrolysis. The synthesis strategy of effective and stable catalyst in this work provide a simple method to fabricate heterogeneous OER catalyst with Schiff base metal complex.

  5. M2-like macrophages are responsible for collagen degradation through a mannose receptor–mediated pathway

    PubMed Central

    Madsen, Daniel H.; Leonard, Daniel; Masedunskas, Andrius; Moyer, Amanda; Jürgensen, Henrik Jessen; Peters, Diane E.; Amornphimoltham, Panomwat; Selvaraj, Arul; Yamada, Susan S.; Brenner, David A.; Burgdorf, Sven; Engelholm, Lars H.; Behrendt, Niels; Holmbeck, Kenn; Weigert, Roberto

    2013-01-01

    Tissue remodeling processes critically depend on the timely removal and remodeling of preexisting collagen scaffolds. Nevertheless, many aspects related to the turnover of this abundant extracellular matrix component in vivo are still incompletely understood. We therefore took advantage of recent advances in optical imaging to develop an assay to visualize collagen turnover in situ and identify cell types and molecules involved in this process. Collagen introduced into the dermis of mice underwent cellular endocytosis in a partially matrix metalloproteinase–dependent manner and was subsequently routed to lysosomes for complete degradation. Collagen uptake was predominantly executed by a quantitatively minor population of M2-like macrophages, whereas more abundant Col1a1-expressing fibroblasts and Cx3cr1-expressing macrophages internalized collagen at lower levels. Genetic ablation of the collagen receptors mannose receptor (Mrc1) and urokinase plasminogen activator receptor–associated protein (Endo180 and Mrc2) impaired this intracellular collagen degradation pathway. This study demonstrates the importance of receptor-mediated cellular uptake to collagen turnover in vivo and identifies a key role of M2-like macrophages in this process. PMID:24019537

  6. M2-like macrophages are responsible for collagen degradation through a mannose receptor-mediated pathway.

    PubMed

    Madsen, Daniel H; Leonard, Daniel; Masedunskas, Andrius; Moyer, Amanda; Jürgensen, Henrik Jessen; Peters, Diane E; Amornphimoltham, Panomwat; Selvaraj, Arul; Yamada, Susan S; Brenner, David A; Burgdorf, Sven; Engelholm, Lars H; Behrendt, Niels; Holmbeck, Kenn; Weigert, Roberto; Bugge, Thomas H

    2013-09-16

    Tissue remodeling processes critically depend on the timely removal and remodeling of preexisting collagen scaffolds. Nevertheless, many aspects related to the turnover of this abundant extracellular matrix component in vivo are still incompletely understood. We therefore took advantage of recent advances in optical imaging to develop an assay to visualize collagen turnover in situ and identify cell types and molecules involved in this process. Collagen introduced into the dermis of mice underwent cellular endocytosis in a partially matrix metalloproteinase-dependent manner and was subsequently routed to lysosomes for complete degradation. Collagen uptake was predominantly executed by a quantitatively minor population of M2-like macrophages, whereas more abundant Col1a1-expressing fibroblasts and Cx3cr1-expressing macrophages internalized collagen at lower levels. Genetic ablation of the collagen receptors mannose receptor (Mrc1) and urokinase plasminogen activator receptor-associated protein (Endo180 and Mrc2) impaired this intracellular collagen degradation pathway. This study demonstrates the importance of receptor-mediated cellular uptake to collagen turnover in vivo and identifies a key role of M2-like macrophages in this process.

  7. Structures of actin-like ParM filaments show architecture of plasmid-segregating spindles.

    PubMed

    Bharat, Tanmay A M; Murshudov, Garib N; Sachse, Carsten; Löwe, Jan

    2015-07-02

    Active segregation of Escherichia coli low-copy-number plasmid R1 involves formation of a bipolar spindle made of left-handed double-helical actin-like ParM filaments. ParR links the filaments with centromeric parC plasmid DNA, while facilitating the addition of subunits to ParM filaments. Growing ParMRC spindles push sister plasmids to the cell poles. Here, using modern electron cryomicroscopy methods, we investigate the structures and arrangements of ParM filaments in vitro and in cells, revealing at near-atomic resolution how subunits and filaments come together to produce the simplest known mitotic machinery. To understand the mechanism of dynamic instability, we determine structures of ParM filaments in different nucleotide states. The structure of filaments bound to the ATP analogue AMPPNP is determined at 4.3 Å resolution and refined. The ParM filament structure shows strong longitudinal interfaces and weaker lateral interactions. Also using electron cryomicroscopy, we reconstruct ParM doublets forming antiparallel spindles. Finally, with whole-cell electron cryotomography, we show that doublets are abundant in bacterial cells containing low-copy-number plasmids with the ParMRC locus, leading to an asynchronous model of R1 plasmid segregation.

  8. The continuing challenges of translational research: clinician-scientists' perspective.

    PubMed

    Homer-Vanniasinkam, Shervanthi; Tsui, Janice

    2012-01-01

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

  9. The UPBEAT depression and coronary heart disease programme: using the UK medical research council framework to design a nurse-led complex intervention for use in primary care

    PubMed Central

    2012-01-01

    Background Depression is common in coronary heart disease (CHD) and increases the incidence of coronary symptoms and death in CHD patients. Interventions feasible for use in primary care are needed to improve both mood and cardiac outcomes. The UPBEAT-UK programme of research has been funded by the NHS National Institute for Health Research (NIHR) to explore the relationship between CHD and depression and to develop a new intervention for use in primary care. Methods Using the Medical Research Council (MRC) guidelines for developing and evaluating complex interventions, we conducted a systematic review and qualitative research to develop a primary care-based nurse-led intervention to improve mood and cardiac outcomes in patients with CHD and depression. Iterative literature review was used to synthesise our empirical work and to identify evidence and theory to inform the intervention. Results We developed a primary care-based nurse-led personalised care intervention which utilises elements of case management to promote self management. Following biopsychosocial assessment, a personalised care plan is devised. Nurses trained in behaviour change techniques facilitate patients to address the problems important to them. Identification and utilisation of existing resources is promoted. Nurse time is conserved through telephone follow up. Conclusions Application of the MRC framework for complex interventions has allowed us to develop an evidence based intervention informed by patient and clinician preferences and established theory. The feasibility and acceptability of this intervention is now being tested further in an exploratory trial. PMID:23234253

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

    PubMed Central

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

    2016-01-01

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

  11. Mitochondrion-rich cells distribution, Na+/K+-ATPase activity and gill morphometry of the Amazonian freshwater stingrays (Chondrichthyes: Potamotrygonidae).

    PubMed

    Duncan, Wallice P; Silva, Naara F; Fernandes, Marisa N

    2011-09-01

    Detailed measurements of gill area and constituent variables (total filament number, total filament length and mean filament length), and immunolocalization of the α-subunit of Na⁺/K⁺-ATPase and Na⁺/K⁺-ATPase activity were performed on both hemibranchs of all five arches of freshwater potamotrygonid stingrays (Paratrygon aiereba and Potamotrygon sp.). Both species exhibit similar mass-specific gill area, 89.8 ± 6.6 and 91.5 ± 4.3 mm² g⁻¹ for P. aiereba and Potamotrygon sp., respectively. The density of Na⁺/K⁺-ATPase-rich MRCs and Na⁺/K⁺-ATPase activity was higher in the 4th gill arch in both species. The Na⁺/K⁺-ATPase activity was positively correlated to the Na⁺/K⁺-ATPase-rich Na⁺/K⁺-ATPase rich) mitochondrion-rich cell (MRC) distribution among the gill arches of P. aiereba but not in Potamotrygon sp. The levels Na⁺/K⁺-ATPase activity were not correlated to the gill surface area among the arches for both rays' species. Considering that the Na⁺/K⁺-ATPase-rich MRC is the main site for active ion transport in the gill epithelia and Na⁺/K⁺-ATPase activity plays a crucial role in osmoionoregulatory function, we suggesting that 4th gill arch is more relevant for osmoregulation and ion balance in these potamotrygonids.

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

    PubMed

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

    2015-07-01

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

  13. Determinants of health-related quality of life in anti-MAG neuropathy: a cross-sectional multicentre European study.

    PubMed

    Delmont, Emilien; Hiew, Fu Liong; Cassereau, Julien; Aubé-Nathier, Anne-Catherine; Grapperon, Aude-Marie; Attarian, Shahram; Rajabally, Yusuf A

    2017-03-01

    Our objective was to assess determinants of quality of life (QoL) in anti-myelin associated glycoprotein antibody (MAG) neuropathy. The SF-36 questionnaire was assessed in 55 patients, from Marseille, Angers (France) and Birmingham (UK). Routine clinical evaluations included Medical Research Council (MRC) sum score, inflammatory neuropathy cause and treatment (INCAT) sensory score, inflammatory Rasch-built overall disability score (I-RODS), ataxia score, Jamar grip dynamometry, timed 10-m walk, neuropathic pain symptom inventory (NPSI) score, and fatigue severity score (FSS). Physical component summary (PCS) and mental component summary (MCS) of the SF36 questionnaire were significantly lower than in reported normal subjects of both countries (p < 0.001). All SF-36 domains correlated with I-RODS, except MCS for which significance was, however, approached (p = 0.056). PCS correlated with MRC sum score, ataxia score, timed 10-m walk, tremor, Jamar grip dynamometry, NPSI pain score, FSS and level of social support. MCS correlated exclusively with FSS and level of social support. In multivariate regression, PCS was associated independently with I-RODS (p < 0.001) and NPSI pain score (p = 0.011), whereas MCS was associated independently with FSS (p = 0.022). QoL is accurately predicted in anti-MAG neuropathy by the I-RODS and FSS, lending support to their use in clinical and research settings. Effective measures to improve QoL should include tremor and neuropathic pain treatment, fatigue management, and improved social support.

  14. The Oxidative Stress Network of Mycobacterium tuberculosis Reveals Coordination between Radical Detoxification Systems.

    PubMed

    Nambi, Subhalaxmi; Long, Jarukit E; Mishra, Bibhuti B; Baker, Richard; Murphy, Kenan C; Olive, Andrew J; Nguyen, Hien P; Shaffer, Scott A; Sassetti, Christopher M

    2015-06-10

    M. tuberculosis (Mtb) survives a hostile environment within the host that is shaped in part by oxidative stress. The mechanisms used by Mtb to resist these stresses remain ill-defined because the complex combination of oxidants generated by host immunity is difficult to accurately recapitulate in vitro. We performed a genome-wide genetic interaction screen to comprehensively delineate oxidative stress resistance pathways necessary for Mtb to resist oxidation during infection. Our analysis predicted functional relationships between the superoxide-detoxifying enzyme (SodA), an integral membrane protein (DoxX), and a predicted thiol-oxidoreductase (SseA). Consistent with that, SodA, DoxX, and SseA form a membrane-associated oxidoreductase complex (MRC) that physically links radical detoxification with cytosolic thiol homeostasis. Loss of any MRC component correlated with defective recycling of mycothiol and accumulation of cellular oxidative damage. This previously uncharacterized coordination between oxygen radical detoxification and thiol homeostasis is required to overcome the oxidative environment Mtb encounters in the host.

  15. Chloride conductance across toad skin: effects of ionic acclimations and cyclic AMP and relationship to mitochondria-rich cell density.

    PubMed

    Rozman, A; Gabbay, S; Katz, U

    2000-07-01

    The anionic conductance across toad (Bufo viridis) skin was studied using the voltage-clamp technique following long-term (more than 10 days) acclimation to NaCl and KCl solutions. The non-specific baseline conductance was approximately 0.6 mS cm(-)(2) and was similar in skins from all acclimation conditions. The voltage-activated Cl(-) conductance (G(Cl)) was maximal in skins from distilled-water- and KCl-acclimated toads (>3 mS cm(-)(2)) and was greatly reduced following acclimation to NaCl solutions. Cyclic AMP (EC(50)=13 micromol l(-)(1)) and isobutylmethyl xanthine (IBMX) (EC(50)=69 micromol l(-)(1)) exerted different effects on the activated conductance. IBMX only sensitized the activated conductance, whereas cyclic AMP (CPTcAMP) at high concentrations induced an increase in anionic conductance that was insensitive to electrical potential. Furthermore, external Cl(-) was not required for the stimulatory effect of cyclic AMP, and the conductive pathway had low selectivity. The effects of the two agonists were reversible and depended on the acclimation conditions. Following electrical measurements, the skin of the toads was removed and stained with silver to measure mitochondria-rich cell density (D(mrc)). There was no correlation between D(mrc) and Cl(-) conductance in the present study.

  16. Improved antioxidative and cytotoxic activities of chamomile (Matricaria chamomilla) florets fermented by Lactobacillus plantarum KCCM 11613P*

    PubMed Central

    Park, Eun-Hye; Bae, Won-Young; Eom, Su-Jin; Kim, Kee-Tae; Paik, Hyun-Dong

    2017-01-01

    Antioxidative and cytotoxic effects of chamomile (Matricaria chamomilla) fermented by Lactobacillus plantarum were investigated to improve their biofunctional activities. Total polyphenol (TP) content was measured by the Folin-Denis method, and the antioxidant activities were assessed by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method and β-carotene bleaching method. AGS, HeLa, LoVo, MCF-7, and MRC-5 (normal) cells were used to examine the cytotoxic effects by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. The TP content of fermented chamomile reduced from 21.75 to 18.76 mg gallic acid equivalent (mg GAE)/g, but the DPPH radical capturing activity of fermented chamomile was found to be 11.1% higher than that of nonfermented chamomile after 72 h of fermentation. Following the β-carotene bleaching, the antioxidative effect decreased because of a reduction in pH during fermentation. Additionally, chamomile fermented for 72 h showed a cytotoxic effect of about 95% against cancer cells at 12.7 mg solid/ml of broth, but MRC-5 cells were significantly less sensitive against fermented chamomile samples. These results suggest that the fermentation of chamomile could be applied to develop natural antioxidative and anticancer products. PMID:28124843

  17. Longitudinal deteriorations in patient reported outcomes in patients with COPD.

    PubMed

    Oga, Toru; Nishimura, Koichi; Tsukino, Mitsuhiro; Sato, Susumu; Hajiro, Takashi; Mishima, Michiaki

    2007-01-01

    Goals of effective management of patients with chronic obstructive pulmonary disease (COPD) include relieving their symptoms and improving their health status. We examined how such patient reported outcomes would change longitudinally in comparison to physiological outcomes in COPD. One hundred thirty-seven male outpatients with stable COPD were recruited for the study. The subjects health status was evaluated using the St. George's Respiratory Questionnaire (SGRQ) and the Chronic Respiratory Disease Questionnaire (CRQ). Their dyspnoea using the modified Medical Research Council (MRC) scale and their psychological status using the Hospital Anxiety and Depression Scale (HADS) were assessed upon entry and every 6 months thereafter over a 5-year period. Pulmonary function and exercise capacity as evaluated by peak oxygen uptake (VO2) on progressive cycle ergometry were also followed over the same time. Using mixed effects models to estimate the slopes for the changes, scores on the SGRQ, the CRQ, the MRC and the HADS worsened in a statistically significant manner over time. However, changes only weakly correlated with changes in forced expiratory volume in 1s (FEV(1)) and peak (VO2). We demonstrated that although changes in pulmonary function and exercise capacity are well known in patients with COPD, patient reported outcomes such as health status, dyspnoea and psychological status also deteriorated significantly over time. In addition, deteriorations in patient reported outcomes only weakly correlated to changes in physiological indices. To capture the overall deterioration of COPD from the subjective viewpoints of the patients, patient reported outcomes should be followed separately from physiological outcomes.

  18. Heterogeneous fluorescence intermittency in single layer reduced graphene oxide

    NASA Astrophysics Data System (ADS)

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

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

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

    NASA Technical Reports Server (NTRS)

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

    1987-01-01

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

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

    PubMed Central

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

    1996-01-01

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

  1. The effect of a traditional dance training program on dynamic balance of individuals with mental retardation.

    PubMed

    Tsimaras, Vasileios K; Giamouridou, Genovefa A; Kokaridas, Dimitrios G; Sidiropoulou, Maria P; Patsiaouras, Asterios I

    2012-01-01

    The purpose of this study was to evaluate the influence of a Greek traditional dance training program on the dynamic balance of individuals with mental retardation (MR). A total of 17 individuals participated in this study. Ten individuals with mild or moderate MR and 7 individuals with mild or moderate MR who studied in special schools were assigned to intervention (MR-I) and control (MR-C) groups, respectively. Pretraining and posttraining exercise tests were performed to determine the dynamic balance ability. Dynamic balance ability was measured by means of a balance deck (Lafayette, Lafayette, IN, USA) in 30-, 45-, and 60-second intervals. The MR-I group underwent a 16-week Greek traditional dance training program at a frequency of 3 times per week and for a duration of 45 minutes per season. Posttraining results showed that the individuals with MR in the MR-I group improved during treatment, from their baseline scores on dynamic balance measurements (30 seconds: p < 0.01, 45 seconds: p < 0.05, 60 seconds: p < 0.05). The MR-C group did not show any improvement between the 2 measurements. In conclusion, individuals with MR may be able to improve their dynamic balance when performing a systematic and well-designed Greek traditional dance training program.

  2. NEW 145 MHz SOURCE MEASUREMENTS BY PAPER IN THE SOUTHERN SKY

    SciTech Connect

    Jacobs, Daniel C.; Aguirre, James E.; Moore, David F.; Parsons, Aaron R.; Pober, Jonathan C.; Bradley, Richard F.; Parashare, Chaitali R.; Carilli, Chris L.; Gugliucci, Nicole E.; Manley, Jason R.; Van der Merwe, Carel

    2011-06-20

    We present observations from the Precision Array for Probing the Epoch of Reionization (PAPER) in South Africa, observed in 2010 May and September. Using two nights of drift scanning with PAPER's 60{sup 0} FWHM beam we have made a map covering the entire sky below +10{sup 0} declination with an effective center frequency of 145 MHz, a 70 MHz bandwidth, and a resolution of 26'. A 4800 deg{sup 2} region of this large map with the lowest Galactic emission reaches an rms of 0.7 Jy. We establish an absolute flux scale using sources from the 160 MHz Culgoora catalog. Using the 408 MHz Molonglo Reference Catalog (MRC) as a finding survey, we identify counterparts to 480 sources in our maps and compare our fluxes to the MRC and to 332 sources in the Culgoora catalog. For both catalogs, the ratio of PAPER to catalog flux averages to 1, with a standard deviation of 50%. This measured variation is consistent with comparisons between independent catalogs observed at different bands. The PAPER data represent new 145 MHz flux measurements for a large number of sources in the band expected to encompass cosmic reionization and represents a significant step toward establishing a model for removing foregrounds to the reionization signal.

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

    PubMed

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

    2003-07-01

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

  4. Detection of 1,N(2)-propano-2'-deoxyguanosine adducts in genomic DNA by ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry in combination with stable isotope dilution.

    PubMed

    Zhang, Ning; Song, Yuanyuan; Wu, Danni; Xu, Tian; Lu, Meiling; Zhang, Weibing; Wang, Hailin

    2016-06-10

    Crotonaldehyde (Cro) is one of widespread and genotoxic α,β-unsaturated aldehydes and can react with the exocyclic amino group of 2'-deoxyguanosine (dG) in genomic DNA to form 1,N(2)-propano-2'-deoxyguanosine (ProdG) adducts. In this study, two diastereomers of high purity were prepared, including non-isotope and stable isotope labeled ProdG adducts, and exploited stable isotope dilution-based calibration method. By taking advantage of synthesized ProdG standards, we developed a sensitive ultrahigh performance liquid chromatography-electrospray ionization-tandem mass spectrometry (UHPLC-ESI-MS/MS) method for accurate quantification of two diastereomers of ProdG adducts. In addition to optimization of the UHPLC separation, ammonium bicarbonate (NH4HCO3) was used as additive in the mobile phase for enhancing the ionization efficiency to ProdG adducts and facilitating MS detection. The limits of detection (LODs, S/N=3) and the limits of quantification (LOQs, S/N=10) are estimated about 50 amol and 150 amol, respectively. By the use of the developed method, both diastereomers of ProdG adducts can be detected in untreated human MRC5 cells with a frequency of 2.4-3.5 adducts per 10(8) nucleotides. Crotonaldehyde treatment dramatically increases the levels of ProdG adducts in human MRC5 in a concentration-dependent manner.

  5. VARS2 and TARS2 mutations in patients with mitochondrial encephalomyopathies.

    PubMed

    Diodato, Daria; Melchionda, Laura; Haack, Tobias B; Dallabona, Cristina; Baruffini, Enrico; Donnini, Claudia; Granata, Tiziana; Ragona, Francesca; Balestri, Paolo; Margollicci, Maria; Lamantea, Eleonora; Nasca, Alessia; Powell, Christopher A; Minczuk, Michal; Strom, Tim M; Meitinger, Thomas; Prokisch, Holger; Lamperti, Costanza; Zeviani, Massimo; Ghezzi, Daniele

    2014-08-01

    By way of whole-exome sequencing, we identified a homozygous missense mutation in VARS2 in one subject with microcephaly and epilepsy associated with isolated deficiency of the mitochondrial respiratory chain (MRC) complex I and compound heterozygous mutations in TARS2 in two siblings presenting with axial hypotonia and severe psychomotor delay associated with multiple MRC defects. The nucleotide variants segregated within the families, were absent in Single Nucleotide Polymorphism (SNP) databases and are predicted to be deleterious. The amount of VARS2 and TARS2 proteins and valyl-tRNA and threonyl-tRNA levels were decreased in samples of afflicted patients according to the genetic defect. Expression of the corresponding wild-type transcripts in immortalized mutant fibroblasts rescued the biochemical impairment of mitochondrial respiration and yeast modeling of the VARS2 mutation confirmed its pathogenic role. Taken together, these data demonstrate the role of the identified mutations for these mitochondriopathies. Our study reports the first mutations in the VARS2 and TARS2 genes, which encode two mitochondrial aminoacyl-tRNA synthetases, as causes of clinically distinct, early-onset mitochondrial encephalopathies.

  6. Power Scaling of Uplink Massive MIMO Systems With Arbitrary-Rank Channel Means

    NASA Astrophysics Data System (ADS)

    Zhang, Qi; Jin, Shi; Wong, Kai-Kit; Zhu, Hongbo; Matthaiou, Michail

    2014-10-01

    This paper investigates the uplink achievable rates of massive multiple-input multiple-output (MIMO) antenna systems in Ricean fading channels, using maximal-ratio combining (MRC) and zero-forcing (ZF) receivers, assuming perfect and imperfect channel state information (CSI). In contrast to previous relevant works, the fast fading MIMO channel matrix is assumed to have an arbitrary-rank deterministic component as well as a Rayleigh-distributed random component. We derive tractable expressions for the achievable uplink rate in the large-antenna limit, along with approximating results that hold for any finite number of antennas. Based on these analytical results, we obtain the scaling law that the users' transmit power should satisfy, while maintaining a desirable quality of service. In particular, it is found that regardless of the Ricean $K$-factor, in the case of perfect CSI, the approximations converge to the same constant value as the exact results, as the number of base station antennas, $M$, grows large, while the transmit power of each user can be scaled down proportionally to $1/M$. If CSI is estimated with uncertainty, the same result holds true but only when the Ricean $K$-factor is non-zero. Otherwise, if the channel experiences Rayleigh fading, we can only cut the transmit power of each user proportionally to $1/\\sqrt M$. In addition, we show that with an increasing Ricean $K$-factor, the uplink rates will converge to fixed values for both MRC and ZF receivers.

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

    USGS Publications Warehouse

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

    2007-01-01

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

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

    PubMed

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

    2013-10-01

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

  9. Improved antioxidative and cytotoxic activities of chamomile (Matricaria chamomilla) florets fermented by Lactobacillus plantarum KCCM 11613P.

    PubMed

    Park, Eun-Hye; Bae, Won-Young; Eom, Su-Jin; Kim, Kee-Tae; Paik, Hyun-Dong

    Antioxidative and cytotoxic effects of chamomile (Matricaria chamomilla) fermented by Lactobacillus plantarum were investigated to improve their biofunctional activities. Total polyphenol (TP) content was measured by the Folin-Denis method, and the antioxidant activities were assessed by the 1,1-diphenyl-2-picrylhydrazyl (DPPH) method and β-carotene bleaching method. AGS, HeLa, LoVo, MCF-7, and MRC-5 (normal) cells were used to examine the cytotoxic effects by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium (MTT) assay. The TP content of fermented chamomile reduced from 21.75 to 18.76 mg gallic acid equivalent (mg GAE)/g, but the DPPH radical capturing activity of fermented chamomile was found to be 11.1% higher than that of nonfermented chamomile after 72 h of fermentation. Following the β-carotene bleaching, the antioxidative effect decreased because of a reduction in pH during fermentation. Additionally, chamomile fermented for 72 h showed a cytotoxic effect of about 95% against cancer cells at 12.7 mg solid/ml of broth, but MRC-5 cells were significantly less sensitive against fermented chamomile samples. These results suggest that the fermentation of chamomile could be applied to develop natural antioxidative and anticancer products.

  10. Development of clinically meaningful complex interventions - the contribution of qualitative research.

    PubMed

    Ludvigsen, Mette Spliid; Meyer, Gabriele; Hall, Elisabeth; Fegran, Liv; Aagaard, Hanne; Uhrenfeldt, Lisbeth

    2013-06-01

    The debate about the "right" methods and designs for nursing research is on-going. According to international surveys, studies on the effectiveness and safety of nursing interventions are rare. Since nursing practice deals daily with interventions, nurses ostensibly expose hospital patients and nursing home residents frequently to unproven therapeutic and preventive nursing interventions. Nursing interventions are predominately of a complex nature, consisting of several components depending on and interacting with each other and their complex contextual factors. Thus, evaluation studies are often challenging and need especially careful development, ambitious designs and systematic evaluations. The UK Medical Research Council (MRC) has proposed a framework, where qualitative and quantitative research rely on each other in order to develop theory-based complex interventions, prepare and conduct their optimal delivery, explain how the interventions work and which conditions contributed in case they did not work. The present essay outlines the points where qualitative research contributes towards the development and evaluation of complex interventions. First, the UK MRC framework is introduced, and secondly it is illustrated where qualitative research should necessarily be located using examples from a handful of qualitative studies. Future clinically meaningful and implementable nursing interventions should best be developed by research groups with both excellent qualitative and quantitative research skills.

  11. De novo AML exhibits greater microenvironment dysregulation compared to AML with myelodysplasia-related changes

    PubMed Central

    Lopes, Matheus Rodrigues; Pereira, João Kleber Novais; de Melo Campos, Paula; Machado-Neto, João Agostinho; Traina, Fabiola; Saad, Sara T. Olalla; Favaro, Patricia

    2017-01-01

    The interaction between the bone marrow microenvironment and malignant hematopoietic cells can result in the protection of leukemia cells from chemotherapy in both myelodysplastic syndromes (MDS) and acute myeloid leukemia (AML). We, herein, characterized the changes in cytokine expression and the function of mesenchymal stromal cells (MSC) in patients with MDS, AML with myelodysplasia-related changes (MRC), a well-recognized clinical subtype of secondary AML, and de novo AML. We observed a significant inhibitory effect of MDS-MSC on T lymphocyte proliferation and no significant differences in any of the cytokines tested. AML-MSC inhibited T-cell proliferation only at a very low MSC/T cell ratio. When compared to the control, AML-MRCderived MSC presented a significant increase in IL6 expression, whereas de novo AML MSC presented a significant increase in the expression levels of VEGFA, CXCL12, RPGE2, IDO, IL1β, IL6 and IL32, followed by a decrease in IL10 expression. Furthermore, data indicate that IL-32 regulates stromal cell proliferation, has a chemotactic potential and participates in stromal cell crosstalk with leukemia cells, which could result in chemoresistance. Our results suggest that the differences between AML-MRC and de novo AML also extend into the leukemic stem cell niche and that IL-32 can participate in the regulation of the bone marrow cytokine milieu. PMID:28084439

  12. Advanced bearing materials for cryogenic aerospace engine turbopump requirements

    NASA Technical Reports Server (NTRS)

    Friedman, G.; Bhat, B. N.

    1986-01-01

    The properties of eleven alloys were investigated to select an improved bearing material for the High Pressure Oxygen Turbo Pump which delivers liquid oxygen to the Space Shuttle Main Engine. The alloys, selected through detailed literature analysis, X 405, MRC-2001, T440V, 14-4/6V, D-5, V-M Pyromet 350, Stellite 3, FerroTic CS-40, Tribaloy 800, WD-65, and CBS-600. The alloys were tested in hardness, corrosion resistance, wear resistance, fatigue resistance, and fracture toughness tests, and their performance was compared with the baseline 440C test alloy. As a result, five alloys were eliminated, leaving the remaining six (X 405, MRC-2001, T440V, 14-4/6V, D-5, and WD-65 to be evaluated in the next phase of NASA tests which will include fracture toughness, rolling contact fatigue, wear resistance, and corrosion resistance. From these, three alloys will be selected, which will be made into ninety bearings for subsequent testing.

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

    PubMed Central

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

    2016-01-01

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

  14. Comorbidity, systemic inflammation and outcomes in the ECLIPSE cohort.

    PubMed

    Miller, Joy; Edwards, Lisa D; Agustí, Alvar; Bakke, Per; Calverley, Peter M A; Celli, Bartolome; Coxson, Harvey O; Crim, Courtney; Lomas, David A; Miller, Bruce E; Rennard, Steve; Silverman, Edwin K; Tal-Singer, Ruth; Vestbo, Jørgen; Wouters, Emiel; Yates, Julie C; Macnee, William

    2013-09-01

    Comorbidities, are common in COPD, have been associated with poor outcomes and are thought to relate to systemic inflammation. To investigate comorbidities in relation to systemic inflammation and outcomes we recorded comorbidities in a well characterized cohort (ECLIPSE study) for 2164 clinically stable COPD subjects, 337 smokers and 245 non-smokers with normal lung function. COPD patients had a higher prevalence of osteoporosis, anxiety/panic attacks, heart trouble, heart attack, and heart failure, than smokers or nonsmokers. Heart failure (Hazard Ratio [HR] 1.9, 95% Confidence Interval [CI] 1.3-2.9), ischemic heart disease (HR 1.5, 95% CI 1.1-2.0), heart disease (HR 1.5, 95% CI 1.2-2.0), and diabetes (HR 1.7, 95% CI 1.2-2.4) had increased odds of mortality when coexistent with COPD. Multiple comorbidities had accumulative effect on mortality. COPD and cardiovascular disease was associated with poorer quality of life, higher MRC dyspnea scores, reduced 6MWD, higher BODE index scores. Osteoporosis, hypertension and diabetes were associated with higher MRC dyspnea scores and reduced 6MWD. Higher blood concentrations of fibrinogen, IL-6 and IL-8 levels occurred in those with heart disease. Comorbidity is associated with poor clinical outcomes in COPD. The comorbidities of heart disease, hypertension and diabetes are associated with increased systemic inflammation.

  15. Issues in the development of a 10 MBPS K=15 Viterbi decoder

    NASA Technical Reports Server (NTRS)

    Osborne, William P.

    1994-01-01

    The NMSU Telemetry Center, in collaboration with the NASA Microelectronics Center (MRC) at UNM, has completed a study of the feasibility of building a constraint length 15, rate 1/2 Viterbi Decoder (or BVD) to operate at a rate of 10 Mbps. The BVD, if built, would make TDRSS more accessible to all users, small satellites in particular, by providing an additional 2 dB of link margin, relative to the use of the standard constraint length 7 decoder. The study included the following: review of the 1 Mbps BVD built by the Jet Propulsion Laboratory (JPL), currently the only BVD in existence; development of Specifications for the basic processing unit of the BVD (MRC); analytical Determination of performance of large constraint length convolutional codes; investigation of the impact of processor design on the overall system design; and two feasible packaging technologies, proposed by Cincinnati Electronics of Ohio. It was concluded that while the construction of the BVD is feasible, it will require the most advanced packaging technology currently available, and that the project would be best accomplished in an industrial facility. While the size, complexity, and power requirements of the BVD will be extreme, these will impact only the ground station. The spacecraft will incur a minor change in the encoder design, and the increased coding gain will allow a satellite to operate with a smaller antenna.

  16. Persistent disabling breathlessness in chronic obstructive pulmonary disease

    PubMed Central

    Sundh, Josefin; Ekström, Magnus

    2016-01-01

    Objective To determine the prevalence, change in breathlessness status over time, and risk factors for disabling and persistent disabling breathlessness in relation to treatments in chronic obstructive pulmonary disease (COPD). Materials and methods Longitudinal analysis of data from the Swedish National Register of COPD with breathlessness measured using modified Medical Research Council (mMRC) scores at two subsequent visits. Prevalence of disabling breathlessness (mMRC ≥2 at baseline) and persistent disabling breathlessness (disabling breathlessness at baseline and follow-up) was investigated in relation to COPD treatment. Risk factors for disabling breathlessness, change from non-disabling to disabling breathlessness, and persistent disabling breathlessness were analyzed using multiple logistic regression. Results A total of 1,689 patients were included in the study with a median follow-up of 12 months (interquartile range: 4 months). Prevalence of disabling breathlessness was 54% at baseline. Persistent disabling breathlessness was present in 43% of patients despite treatment and in 74% of patients despite combined inhaled triple therapy and physiotherapy. Risk factors for disabling breathlessness or change to disabling breathlessness were higher age, lower lung function, frequent exacerbations, obesity, heart failure, depression, and hypoxic respiratory failure (all P<0.05). Persistent disabling breathlessness was associated with lower lung function and ischemic heart disease (all P<0.05). Conclusion Disabling breathlessness is common in COPD despite treatment, which calls for improved symptomatic treatments and consideration of factors influencing disabling breathlessness. Factors influencing disabling breathlessness should be considered for COPD management. PMID:27877034

  17. Microbial community response to addition of polylactate compounds to stimulate hexavalent chromium reduction in groundwater.

    PubMed

    Brodie, Eoin L; Joyner, Dominique C; Faybishenko, Boris; Conrad, Mark E; Rios-Velazquez, Carlos; Malave, Josue; Martinez, Ramon; Mork, Benjamin; Willett, Anna; Koenigsberg, Steven; Herman, Donald J; Firestone, Mary K; Hazen, Terry C

    2011-10-01

    To evaluate the efficacy of bioimmobilization of Cr(VI) in groundwater at the Department of Energy Hanford site, we conducted a series of microcosm experiments using a range of commercial electron donors with varying degrees of lactate polymerization (polylactate). These experiments were conducted using Hanford Formation sediments (coarse sand and gravel) immersed in Hanford groundwater, which were amended with Cr(VI) and several types of lactate-based electron donors (Hydrogen Release Compound, HRC; primer-HRC, pHRC; extended release HRC) and the polylactate-cysteine form (Metal Remediation Compound, MRC). The results showed that polylactate compounds stimulated an increase in bacterial biomass and activity to a greater extent than sodium lactate when applied at equivalent carbon concentrations. At the same time, concentrations of headspace hydrogen and methane increased and correlated with changes in the microbial community structure. Enrichment of Pseudomonas spp. occurred with all lactate additions, and enrichment of sulfate-reducing Desulfosporosinus spp. occurred with almost complete sulfate reduction. The results of these experiments demonstrate that amendment with the pHRC and MRC forms result in effective removal of Cr(VI) from solution most likely by both direct (enzymatic) and indirect (microbially generated reductant) mechanisms.

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

    PubMed

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

    2016-08-01

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

  19. As Depressing As It Was Predictable?

    PubMed Central

    Timmermann, Carsten

    2007-01-01

    Summary In recent years lung cancer specialists have complained that due to stigma resulting from the association of the disease with smoking, theirs is a neglected field. This paper demonstrates that in the 1950s and 1960s, when the British Medical Research Council (MRC) started to organize clinical trials for various forms of cancer, this was not the case. Rather, the organizers of these trials saw lung cancer as a particularly promising object of research, for much was known about the disease. The cancer trials were part of a strategy to use the Randomized Controlled Trial (RCT) technology to cement the role of the MRC as the dominant body overseeing medical research in Britain. The organization of the trials, however, turned out to be very difficult, due to ethical problems and the dominance of one form of therapy, surgery. The trial results were deeply disappointing. I argue that these frustrating results contributed to the notion of hopelessness that has come to surround lung cancer, and to the shift of focus from cure to prevention that was triggered by epidemiologic studies identifying tobacco smoke as the main cause of the disease. The paper deals with an important episode in the history of clinical cancer research in postwar Britain, illustrating the ethical and practical problems faced by the organizers. PMID:17369673

  20. Combretastatin A-4 derivatives: synthesis and evaluation of 2,4,5-triaryl-1H-imidazoles as potential agents against H1299 (non-small cell lung cancer cell).

    PubMed

    Tseng, Chih-Hua; Li, Chi-Yi; Chiu, Chien-Chih; Hu, Huei-Ting; Han, Chein-Hwa; Chen, Yeh-Long; Tzeng, Cherng-Chyi

    2012-11-01

    A number of 2,4,5-triaryl-1H-imidazole derivatives were synthesized and evaluated for their antiproliferative activities against the growth of five cell lines including three non-small cell lung cancers (H460, H1299, and A549), one breast cancer (MCF-7), and one normal diploid embryonic lung cell line (MRC-5). Preliminary results indicated that both 2-(5-bromofuran-2-yl)-4,5-bis{4-[3-(dimethylamino) propoxy] phenyl}-1H-imidazole (10f) and 4,5-bis{4-[3-(dimethylamino)propoxy]phenyl}-2-(5-nitrofuran-2-yl)-1H -imidazole (10g) were selectively active against the growth of H1229 with an IC(50) of less than 0.1 μM, thus were more active than topotecan (IC(50) > 10.0 μ M). However, both 10f and 10g exhibited only marginal cytotoxicity against H460, A549, MCF-7, and MRC-5 requiring an IC (50) of at least 4.16 μM. Our results also indicated that 10f induced H1299 cell cycle arrest at G0/G1 through the inactivation of p38 MAPK, JNK, ERK, as well as the expression of SIRT1 and survivin. These results suggested that 10f might have therapeutic potential against H1299 (non-small cell lung cancer cell).

  1. Automated linkage analysis in psychiatric disorders

    SciTech Connect

    He, L.; Mansfield, D.C.; Brown, A.F.; Green, D.K.

    1995-06-19

    A genome-wide search for linkage of microsatellite markers to chromosomal loci containing genes responsible for the major psychoses is a laborious task which can be carried out with greater speed and economy by introducing automation to several steps in the procedure. We describe the use of the Automated Linkage Preprocessor (ALP) program for the computer analysis of the waveform generated by fluorescein-labelled markers after electrophoretic separation. (To obtain a copy send a request to A.F. Brown at the below MRC address or use Anonymous FTP to ftp.hgu.mrc.ac.uk. Software is in directory pub/ALP.) The program runs on a PC in the Microsoft Windows environment, and is used in conjunction with an automated laser fluorescence (ALF) sequencer (Pharmacia) and its Fragment Manager{trademark} software to detect and size the PCR products, filter out peaks of fluorescence due to nonallele fragments, and generate genotypes in a format suitable for direct input to standard linkage analysis programs. The method should offer the advantages of speed, accuracy, and reduced cost. Its use in linkage studies in a large family with manic-depressive illness is discussed. 14 refs., 3 figs., 1 tab.

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

    PubMed

    Tesfaye, Solomon

    2016-04-01

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

  3. Analysis of replication profiles reveals key role of RFC-Ctf18 in yeast replication stress response.

    PubMed

    Crabbé, Laure; Thomas, Aubin; Pantesco, Véronique; De Vos, John; Pasero, Philippe; Lengronne, Armelle

    2010-11-01

    Maintenance of genome integrity relies on surveillance mechanisms that detect and signal arrested replication forks. Although evidence from budding yeast indicates that the DNA replication checkpoint (DRC) is primarily activated by single-stranded DNA (ssDNA), studies in higher eukaryotes have implicated primer ends in this process. To identify factors that signal primed ssDNA in Saccharomyces cerevisiae, we have screened a collection of checkpoint mutants for their ability to activate the DRC, using the repression of late origins as readout for checkpoint activity. This quantitative analysis reveals that neither RFC(Rad24) and the 9-1-1 clamp nor the alternative clamp loader RFC(Elg1) is required to signal paused forks. In contrast, we found that RFC(Ctf18) is essential for the Mrc1-dependent activation of Rad53 and for the maintenance of paused forks. These data identify RFC(Ctf18) as a key DRC mediator, potentially bridging Mrc1 and primed ssDNA to signal paused forks.

  4. A combined Poisson cluster-cascade stochastic model for temporal precipitation

    NASA Astrophysics Data System (ADS)

    Paschalis, A.; Molnar, P.; Fatichi, S.; Burlando, P.

    2011-12-01

    Stochastic precipitation simulation is a fundamental tool in hydrology to obtain high resolution time series of precipitation for ungauged basins, or sites where data records are short or of coarse temporal resolution. Different stochastic modeling tools have been developed in the last decades in order to simulate precipitation time series that satisfactorily reproduce observed statistical properties. The two most widely used classes of models in hydrology are Poisson cluster processes (e.g. Neyman-Scott, Bartlett-Lewis models) and multiplicative random cascades (MRC). It has been recognized that these two classes of models behave differently across time scales. The Poisson cluster models are generally more suitable for coarser time scales (typically larger than one hour) since they reproduce the clustering nature of precipitation events. However, due to their construction they are unable to capture small scale within storm variability. On the other hand, MRCs have been widely used as disaggregation tools due to their ability to capture small scale features of precipitation through the self-similar cascading structure across scales which phenomenologically resembles the energy cascade in turbulence. For precipitation this self-similar behavior breaks at coarser temporal scales (typically larger than one day), which is a limitation for MRC models. A combined Poisson cluster-cascade stochastic model is presented to simulate point precipitation across a wide range of temporal scales, from annual down to few minutes. The model attempts to exploit the strengths of both modeling methods. It consists of a Poisson cluster model as external process for coarser temporal scales which is coupled with a MRC model used as a downscaling procedure to capture variability at high temporal resolutions of hydrological interest (i.e. on the order of minutes). First we investigate the performance of the two classes of models across scales in terms of marginal intensity distributions

  5. Final Report - Sulfate Solubility in RPP-WTP HLW Glasses, VSL-06R6780-1, Rev. 0

    SciTech Connect

    Kruger, Albert A.; Pegg, I. L.; Feng, A.; Gan, H.; Kot, W. K.

    2013-12-03

    This report describes the results of work and testing specified by Test Specifications 24590-HLW-TSP-RT-01-006 Rev 1, Test Plans VSL-02T7800-1 Rev 1 and Test Exceptions 24590-HLW-TEF-RT-05-00007. The work and any associated testing followed established quality assurance requirements and were conducted as authorized. The descriptions provided in this report are an accurate account of both the conduct of the work and the data collected. Results required by the Test Plans are reported. Also reported are any unusual or anomalous occurrences that are different from the starting hypotheses. The test results and this report have been reviewed and verified.

  6. Final Report - ILAW PCT, VHT, Viscosity, and Electrical Conductivity Model Development, VSL-07R1230-1

    SciTech Connect

    Kruger, Albert A.; Cooley, S. K.; Joseph, I.; Pegg, I. L.; Piepel, G. F.; Gan, H.; Muller, I.

    2013-12-17

    This report describes the results of work and testing specified by the Test Specifications (24590-LAW-TSP-RT-01-013 Rev.1 and 24590-WTP-TSP-RT-02-001 Rev.0), Test Plans (VSL-02T4800-1 Rev.1 & TP-RPP-WTP-179 Rev.1), and Text Exception (24590-WTP-TEF-RT-03-040). The work and any associated testing followed established quality assurance requirements and conducted as authorized. The descriptions provided in this test report are an accurate account of both the conduct of the work and the data collected. Results required by the Test Plans are reported. Also reported are any unusual or anomalous occurrences that are different from the starting hypotheses. The test results and this report have been reviewed and verified.

  7. Brief of the Canadian Society for Clinical Investigation to the science and technology review.

    PubMed

    1995-02-01

    In the context of new realities, perceptions, and concerns, it is fitting that the government has undertaken this Science and Technology Review, questioning not only how much to spend but also the justification and the best ways to carry out federally-funded research. We share the government's concern about the lack of economic competitiveness of our industries and agree that government-sponsored research should make a bigger contribution to the nation's global economic position. The CSCI, which represents the clinical investigators/scientists in this country, is grateful for having been given the opportunity to make this "tour d'horizon" of Canadian clinical research. In this brief, we have attempted to articulate the needs for, and the benefits of, basic biomedical research because it is the only type of research which will provide us with final answers. However, it should be more closely articulated with applied research, as well as with epidemiological, evaluative, and operational approaches which have been neglected. This brief has emphasized that CSCI is committed to PUTTING MORE SCIENCE INTO MEDICINE by encouraging a greater flow of discoveries from the laboratory research bench to the bedside and the community. We made the point that there is a crisis in patient-oriented research and a decrease of young physicians opting for research careers. The Royal College of Physicians and Surgeons of Canada and the MRC are responsive to this situation, which may compromise our capacity to discharge our broader mission. The MRC has given itself valid instruments to foster the creation of wealth through special programs such as the NCE, the University/Industry program, and the MRC-PMAC partnership. Some refining is in order, and close scrutiny of outcome is essential. Both the academic community and industry have their share of responsibility for the less-than-optimal transfer of knowledge to the market place. Lack of venture capital is also a serious issue. A unified

  8. Improving the quality of discharge summaries: implementing updated Academy of Medical Royal Colleges standards at a district general hospital.

    PubMed

    May-Miller, Hannah; Hayter, Joanne; Loewenthal, Lola; Hall, Louis; Hilbert, Rebecca; Quinn, Michael; Pearson, Nicola; Patel, Alisha; Law, Rebekah

    2015-01-01

    Quality of documentation is harder to quantify and incentivise, but it has a significant impact on patient care. Good discharge summaries facilitate continuity between secondary and primary care. The junior doctors' forum led this project to improve the quality of electronic discharge summaries (eDS). Baseline measurement revealed significant room for improvement. We measured the quality of 10 summaries per month (across all inpatient specialties), against 23 indicators from the revised Academy of Medical Royal Colleges (AoMRC) standards (2013) that were prioritised by GPs as a "minimum dataset". Junior doctors felt that the Trust's dual eDS systems were responsible for great variation in quality. This was confirmed by the results of a comparison audit of the systems in April 2014: one system greatly outperformed the other (57% mean compliance with iSoft clinical management (iCM) based system vs. 77% with InfoPath-based system). We recommended that the Trust move to a single eDS system, decommissioning the iCM-based system, and this proposal was approved by several Trust committees. We worked with information services, junior doctors, general practitioners and hospital physicians to develop and implement a generic template to further improve compliance with AoMRC standards. In August 2014, the iCM-based system was withdrawn, the new template went live, and training was delivered, coinciding with the changeover of junior doctors to minimise disruption. Median compliance increased from 66.7% to 77.8%. Quality of discharge summaries had improved across the specialties. There was a reduction in the number of complaints and positive qualitative feedback from general practitioners and junior doctors. Completion of discharge summaries within 24 hours was not affected by this change. There is still more to be done to improve quality; average compliance with the full AoMRC standards (39 indicators) is 59.5%. With the approval of the Trust executive committee further plan

  9. Prognostic Importance of Dyspnea for Cardiovascular Outcomes and Mortality in Persons without Prevalent Cardiopulmonary Disease: The Atherosclerosis Risk in Communities Study

    PubMed Central

    Santos, Mario; Kitzman, Dalane W.; Matsushita, Kunihiro; Loehr, Laura; Sueta, Carla A.; Shah, Amil M.

    2016-01-01

    Background The relationship between dyspnea and incident heart failure (HF) and myocardial infarction (MI) among patients without previously diagnosed cardiopulmonary disease is unclear. We studied the prognostic relevance of self-reported dyspnea for cardiovascular outcomes and all-cause mortality in persons without previously diagnosed cardiopulmonary disease. Methods and Results We studied 10 881 community-dwelling participants (mean age 57±6, 56% women, 25% black) who were free of prevalent cardiopulmonary disease from Atherosclerosis Risk in Communities Study. Dyspnea status at study entry using the modified Medical Research Council (mMRC) scale. The primary outcomes were time to HF, MI or all-cause death. Dyspnea prevalence was 22%, and was mild (mMRC grade 1 or 2) in 21% and moderate-to-severe (mMRC 3 or 4) in 1%. The main correlates of dyspnea were older age, female sex, higher BMI and active smoking. Over a follow-up of 19±5 years, greater self-reported dyspnea severity was associated with worse prognosis. Mild dyspnea was associated with significantly heightened risk of HF (adjusted Hazard Ratio, HR,1.30; 95% CI: 1.16–1.46), MI (adjusted HR 1.34; 95%CI: 1.20–1.50), and death (adjusted HR 1.16; 95%CI: 1.06–1.26), with moderate/severe dyspnea associated with an even greater risk (adjusted HR 2.14, 95%CI: 1.59–2.89; 1.93, 95%CI: 1.41–2.56; 1.96, 95%CI: 1.55–2.48, respectively). Conclusion In community-dwelling persons free of previously diagnosed cardiopulmonary disease, self-reported dyspnea is common and, even when of mild intensity, it is independently associated with a greater risk of incident HF, MI, and death. Our data emphasize the prognostic importance of even mild self-reported dyspnea for cardiovascular outcomes. PMID:27780208

  10. Electrical muscle stimulation prevents critical illness polyneuromyopathy: a randomized parallel intervention trial

    PubMed Central

    2010-01-01

    Introduction Critical illness polyneuromyopathy (CIPNM) is a common complication of critical illness presenting with muscle weakness and is associated with increased duration of mechanical ventilation and weaning period. No preventive tool and no specific treatment have been proposed so far for CIPNM. Electrical muscle stimulation (EMS) has been shown to be beneficial in patients with severe chronic heart failure and chronic obstructive pulmonary disease. Aim of our study was to assess the efficacy of EMS in preventing CIPNM in critically ill patients. Methods One hundred and forty consecutive critically ill patients with an APACHE II score ≥ 13 were randomly assigned after stratification to the EMS group (n = 68) (age:61 ± 19 years) (APACHE II:18 ± 4, SOFA:9 ± 3) or to the control group (n = 72) (age:58 ± 18 years) (APACHE II:18 ± 5, SOFA:9 ± 3). Patients of the EMS group received daily EMS sessions. CIPNM was diagnosed clinically with the medical research council (MRC) scale for muscle strength (maximum score 60, <48/60 cut off for diagnosis) by two unblinded independent investigators. Duration of weaning from mechanical ventilation and intensive care unit (ICU) stay were recorded. Results Fifty two patients could be finally evaluated with MRC; 24 in the EMS group and 28 in the control group. CIPNM was diagnosed in 3 patients in the EMS group as compared to 11 patients in the control group (OR = 0.22; CI: 0.05 to 0.92, P = 0.04). The MRC score was significantly higher in patients of the EMS group as compared to the control group [58 (33 to 60) vs. 52 (2 to 60) respectively, median (range), P = 0.04). The weaning period was statistically significantly shorter in patients of the EMS group vs. the control group [1 (0 to 10) days vs. 3 (0 to 44) days, respectively, median (range), P = 0.003]. Conclusions This study suggests that daily EMS sessions prevent the development of CIPNM in critically ill patients and also result in shorter duration of weaning

  11. Improving the quality of discharge summaries: implementing updated Academy of Medical Royal Colleges standards at a district general hospital

    PubMed Central

    May-Miller, Hannah; Hayter, Joanne; Loewenthal, Lola; Hall, Louis; Hilbert, Rebecca; Quinn, Michael; Pearson, Nicola; Patel, Alisha; Law, Rebekah

    2015-01-01

    Quality of documentation is harder to quantify and incentivise, but it has a significant impact on patient care. Good discharge summaries facilitate continuity between secondary and primary care. The junior doctors’ forum led this project to improve the quality of electronic discharge summaries (eDS). Baseline measurement revealed significant room for improvement. We measured the quality of 10 summaries per month (across all inpatient specialties), against 23 indicators from the revised Academy of Medical Royal Colleges (AoMRC) standards (2013) that were prioritised by GPs as a “minimum dataset”. Junior doctors felt that the Trust's dual eDS systems were responsible for great variation in quality. This was confirmed by the results of a comparison audit of the systems in April 2014: one system greatly outperformed the other (57% mean compliance with iSoft clinical management (iCM) based system vs. 77% with InfoPath-based system). We recommended that the Trust move to a single eDS system, decommissioning the iCM-based system, and this proposal was approved by several Trust committees. We worked with information services, junior doctors, general practitioners and hospital physicians to develop and implement a generic template to further improve compliance with AoMRC standards. In August 2014, the iCM-based system was withdrawn, the new template went live, and training was delivered, coinciding with the changeover of junior doctors to minimise disruption. Median compliance increased from 66.7% to 77.8%. Quality of discharge summaries had improved across the specialties. There was a reduction in the number of complaints and positive qualitative feedback from general practitioners and junior doctors. Completion of discharge summaries within 24 hours was not affected by this change. There is still more to be done to improve quality; average compliance with the full AoMRC standards (39 indicators) is 59.5%. With the approval of the Trust executive committee further

  12. Expression profiles for macrophage alternative activation genes in AD and in mouse models of AD

    PubMed Central

    Colton, Carol A; Mott, Ryan T; Sharpe, Hayley; Xu, Qing; Van Nostrand, William E; Vitek, Michael P

    2006-01-01

    Background Microglia are associated with neuritic plaques in Alzheimer disease (AD) and serve as a primary component of the innate immune response in the brain. Neuritic plaques are fibrous deposits composed of the amyloid beta-peptide fragments (Abeta) of the amyloid precursor protein (APP). Numerous studies have shown that the immune cells in the vicinity of amyloid deposits in AD express mRNA and proteins for pro-inflammatory cytokines, leading to the hypothesis that microglia demonstrate classical (Th-1) immune activation in AD. Nonetheless, the complex role of microglial activation has yet to be fully explored since recent studies show that peripheral macrophages enter an "alternative" activation state. Methods To study alternative activation of microglia, we used quantitative RT-PCR to identify genes associated with alternative activation in microglia, including arginase I (AGI), mannose receptor (MRC1), found in inflammatory zone 1 (FIZZ1), and chitinase 3-like 3 (YM1). Results Our findings confirmed that treatment of microglia with anti-inflammatory cytokines such as IL-4 and IL-13 induces a gene profile typical of alternative activation similar to that previously observed in peripheral macrophages. We then used this gene expression profile to examine two mouse models of AD, the APPsw (Tg-2576) and Tg-SwDI, models for amyloid deposition and for cerebral amyloid angiopathy (CAA) respectively. AGI, MRC1 and YM1 mRNA levels were significantly increased in the Tg-2576 mouse brains compared to age-matched controls while TNFα and NOS2 mRNA levels, genes commonly associated with classical activation, increased or did not change, respectively. Only TNFα mRNA increased in the Tg-SwDI mouse brain. Alternative activation genes were also identified in brain samples from individuals with AD and were compared to age-matched control individuals. In AD brain, mRNAs for TNFα, AGI, MRC1 and the chitinase-3 like 1 and 2 genes (CHI3L1; CHI3L2) were significantly increased

  13. Implications of the GOLD 2011 Disease Severity Classification in the COPDGene Cohort

    PubMed Central

    Han, MeiLan K.; Muellerova, Hana; Curran-Everett, Douglas; Dransfield, Mark; Washko, George; Regan, Elizabeth A.; Bowler, Russell; Beaty, Terri H.; Hokanson, John E.; Lynch, David; Jones, Paul; Anzueto, Antonio; Martinez, Fernando J.; Crapo, James; Silverman, Edwin K.; Make, Barry

    2014-01-01

    Background The 2011 Global Strategy for the Diagnosis, Management, and Prevention of COPD (GOLD) consensus report uses symptoms, exacerbation history and FEV1% to define four categories: A, low symptoms/low risk; B, high symptoms/low risk; C, low symptoms/high risk; and D, high symptoms/high risk where risk refers to exacerbations, hospitalization and death. Our objective was to determine (1) the influence of symptom instrument on category membership and (2) prospective exacerbation risk by category. Methods 4,484 COPD subjects from COPDGene were analyzed. All subjects had smoking history ≥ 10 pack-years and FEV1/FVC<0·7. Categories were defined using the modified Medical Research Council Dyspnea [mMRC] (0–1 versus ≥ 2) and the Saint George’s Respiratory Questionnaire [SGRQ] (≥25 versus <25 as a surrogate for the COPD Assessment Test ≥ 10 versus <10) in addition to COPD exacerbations in the prior year (<2 versus ≥ 2), and FEV1% predicted (≥50 versus <50). Findings Category assignment using mMRC versus SGRQ were similar but not identical. Using the mMRC, category assignments were 34% A, 21% B, 8% C and 38% D and for SGRQ were 29% A, 25% B, 5% C and 41% D (kappa=0·77). Significant heterogeneity in exacerbation rates (exacerbations/person-year) were seen particularly within the D group, depending on the risk factor that determined category assignment (lung function (0·89), prior exacerbation history (1·34) or both (1·86), p<0·001. Interpretations The GOLD classification emphasizes the importance of symptoms and exacerbation risk in assessing COPD severity. The choice of symptom measure influences category assignment. The relative number of subjects with low symptoms and high risk for exacerbations (category C) is low. Differences in exacerbation rates for subjects in the highest risk category D were seen depending on whether risk was based on lung function, exacerbation history or both. PMID:24321803

  14. ALMA finds dew drops in the dusty spider's web

    NASA Astrophysics Data System (ADS)

    Gullberg, Bitten; Lehnert, Matthew D.; De Breuck, Carlos; Branchu, Steve; Dannerbauer, Helmut; Drouart, Guillaume; Emonts, Bjorn; Guillard, Pierre; Hatch, Nina; Nesvadba, Nicole P. H.; Omont, Alain; Seymour, Nick; Vernet, Joël

    2016-06-01

    We present 0.̋5 resolution ALMA detections of the observed 246 GHz continuum, [CI] 3P2→3P1 fine structure line ([CI]2-1), CO(7-6), and H2O lines in the z = 2.161 radio galaxy MRC1138-262, the so-called Spiderweb galaxy. We detect strong [CI]2-1 emission both at the position of the radio core, and in a second component ~4 kpc away from it. The 1100 km s-1 broad [CI]2-1 line in this latter component, combined with its H2 mass of 1.6 × 1010 M⊙, implies that this emission must come from a compact region <60 pc, possibly containing a second active galactic nucleus (AGN). The combined H2 mass derived for both objects, using the [CI]2-1 emission, is 3.3 × 1010 M⊙. The total CO(7-6)/[CI]2-1 line flux ratio of 0.2 suggests a low excitation molecular gas reservoir and/or enhanced atomic carbon in cosmic ray dominated regions. We detect spatially-resolved H2O 211-202 emission - for the first time in a high-z unlensed galaxy - near the outer radio lobe to the east, and near the bend of the radio jet to the west of the radio galaxy. No underlying 246 GHz continuum emission is seen at either position. We suggest that the H2O emission is excited in the cooling region behind slow (10-40 km s-1) shocks in dense molecular gas (103-5 cm-3). The extended water emission is likely evidence of the radio jet's impact on cooling and forming molecules in the post-shocked gas in the halo and inter-cluster gas, similar to what is seen in low-z clusters and other high-z radio galaxies. These observations imply that the passage of the radio jet in the interstellar and inter-cluster medium not only heats gas to high temperatures, as is commonly assumed or found in simulations, but also induces cooling and dissipation, which can lead to substantial amounts of cold dense molecular gas. The formation of molecules and strong dissipation in the halo gas of MRC1138-262 may explain both the extended diffuse molecular gas and the young stars observed around MRC1138-262. The reduced data cubes

  15. Antiviral Activity and Possible Mechanism of Action of Constituents Identified in Paeonia lactiflora Root toward Human Rhinoviruses

    PubMed Central

    Ngan, Luong Thi My; Jang, Myeong Jin; Kwon, Min Jung; Ahn, Young Joon

    2015-01-01

    Human rhinoviruses (HRVs) are responsible for more than half of all cases of the common cold and cost billions of USD annually in medical visits and missed school and work. An assessment was made of the antiviral activities and mechanisms of action of paeonol (PA) and 1,2,3,4,6-penta-O-galloyl-β-D-glucopyranose (PGG) from Paeonia lactiflora root toward HRV-2 and HRV-4 in MRC5 cells using a tetrazolium method and real-time quantitative reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay. Results were compared with those of a reference control ribavirin. Based on 50% inhibitory concentration values, PGG was 13.4 and 18.0 times more active toward HRV-2 (17.89 μM) and HRV-4 (17.33 μM) in MRC5 cells, respectively, than ribavirin. The constituents had relatively high selective index values (3.3–>8.5). The 100 μg/mL PA and 20 μg/mL PGG did not interact with the HRV-4 particles. These constituents inhibited HRV-4 infection only when they were added during the virus inoculation (0 h), the adsorption period of HRVs, but not after 1 h or later. Moreover, the RNA replication levels of HRVs were remarkably reduced in the MRC5 cultures treated with these constituents. These findings suggest that PGG and PA may block or reduce the entry of the viruses into the cells to protect the cells from the virus destruction and abate virus replication, which may play an important role in interfering with expressions of rhinovirus receptors (intercellular adhesion molecule-1 and low-density lipoprotein receptor), inflammatory cytokines (interleukin (IL)-6, IL-8, tumor necrosis factor, interferon beta, and IL-1β), and Toll-like receptor, which resulted in diminishing symptoms induced by HRV. Global efforts to reduce the level of synthetic drugs justify further studies on P. lactiflora root-derived materials as potential anti-HRV products or lead molecules for the prevention or treatment of HRV. PMID:25860871

  16. Assessment of Impact on Students and Teachers of Student-led, inquiry-based planetary science instruction in Grades 3-8

    NASA Astrophysics Data System (ADS)

    Bering, Edgar Andrew; Carlson, Coleen; Nieser, Kenneth; Slagle, Elana

    2015-11-01

    The University of Houston is in the process of developing a flexible program that offers children an in-depth educational experience culminating in the design and construction of their own model Mars rover. The program is called the Mars Rover Model Celebration (MRC). It focuses on students, teachers and parents in grades 3-8. Students design and build a model of a Mars rover to carry out a student selected science mission on the surface of Mars. A total of 195 Mars Rover teachers from the 2012-2013, 2013-2014, and 2014-2015 cohorts were invited to complete the Mars Rover Teacher Evaluation Survey. The survey was administered online and could be taken at the convenience of the participant. So far ~90 teachers have participated with responses still coming in. A total of 1300 students from the 2013-2014 and 2014-2015 cohort were invited to submit brief self-assessments of their participation in the program. Teachers were asked to rate their current level of confidence in their ability to teach specific topics within the Earth and Life Science realms, as well as their confidence in their ability to implement teaching strategies with their students. The most striking increase in this area was the reported 48% of teachers who felt their confidence in teaching “Earth and the solar system and universe” increased “Quite a bit” as a result of their participation in the MRC program. The vast majority of teachers (86-100%) felt somewhat to very confident in their ability to effectively implement all of the listed teaching strategies. The most striking increases were the percentage of teachers who felt their confidence increased “Quite a bit” as a result of their participation in the MRC program in the following areas: “Getting students interested in and curious about science” (63%); “Teaching science as a co-inquirer with students” (56%); and “Continually find better ways to teach science” (59%). Student outcome analysis is pending correlation with

  17. Diagnosis and management of choledocholithiasis in the golden age of imaging, endoscopy and laparoscopy

    PubMed Central

    Costi, Renato; Gnocchi, Alessandro; Di Mario, Francesco; Sarli, Leopoldo

    2014-01-01

    Biliary lithiasis is an endemic condition in both Western and Eastern countries, in some studies affecting 20% of the general population. In up to 20% of cases, gallbladder stones are associated with common bile duct stones (CBDS), which are asymptomatic in up to one half of cases. Despite the wide variety of examinations and techniques available nowadays, two main open issues remain without a clear answer: how to cost-effectively diagnose CBDS and, when they are finally found, how to deal with them. CBDS diagnosis and management has radically changed over the last 30 years, following the dramatic diffusion of imaging, including endoscopic ultrasound (EUS) and magnetic resonance cholangiography (MRC), endoscopy and laparoscopy. Since accuracy, invasiveness, potential therapeutic use and cost-effectiveness of imaging techniques used to identify CBDS increase together in a parallel way, the concept of “risk of carrying CBDS” has become pivotal to identifying the most appropriate management of a specific patient in order to avoid the risk of “under-studying” by poor diagnostic work up or “over-studying” by excessively invasive examinations. The risk of carrying CBDS is deduced by symptoms, liver/pancreas serology and ultrasound. “Low risk” patients do not require further examination before laparoscopic cholecystectomy. Two main “philosophical approaches” face each other for patients with an “intermediate to high risk” of carrying CBDS: on one hand, the “laparoscopy-first” approach, which mainly relies on intraoperative cholangiography for diagnosis and laparoscopic common bile duct exploration for treatment, and, on the other hand, the “endoscopy-first” attitude, variously referring to MRC, EUS and/or endoscopic retrograde cholangiography for diagnosis and endoscopic sphincterotomy for management. Concerning CBDS diagnosis, intraoperative cholangiography, EUS and MRC are reported to have similar results. Regarding management, the recent

  18. Coil therapy for patients with severe emphysema and bilateral incomplete fissures – effectiveness and complications after 1-year follow-up: a single-center experience

    PubMed Central

    Kontogianni, Konstantina; Gerovasili, Vasiliki; Gompelmann, Daniela; Schuhmann, Maren; Hoffmann, Hans; Heussel, Claus Peter; Herth, Felix JF; Eberhardt, Ralf

    2017-01-01

    Background Lung volume reduction coil (LVRC) treatment is established in daily endoscopic lung volume reduction routine. The aim of this study was to evaluate the safety and efficacy of LVRC treatment. Patients and methods This was a retrospective analysis of 86 patients (male/female: 40/46, mean age: 64±7 years) with severe COPD and bilateral incomplete fissures. A total of 10 coils were unilaterally implanted in a single lobe, and 28 out of 86 patients were treated bilaterally. At 90-, 180-, and 365-day follow-up, changes in pulmonary function test (PFT), 6-minute walk test (6MWT) and modified Medical Research Council (mMRC) dyspnea scale, as well as possible complications, were recorded. Results At 90 days, the forced expiratory volume in 1 second did improve (P<0.001), but the improvement was not sustained at the 180- and 365-day follow-up (baseline: 0.71±0.21 vs 0.77±0.23 vs 0.73±0.22 vs 0.70±0.18 L). Both vital capacity and residual volume improved significantly (P<0.001) at the 90- and 180-day follow-up, but the improvement was lost after 365 days. Total lung capacity decreased at the 90-day follow-up but returned to baseline values at the 180- and 365-day follow-up. 6MWT (P=0.01) and mMRC (P=0.007) also improved at 90 and 180 days (Δ6MWT of 31±54 and 20±60 m, respectively), but the improvement was also lost at the 365-day follow-up. No significant further improvement was evident at any point in the follow-up after the second procedure. A total of 4 out of 86 patients passed away due to complications. Significant complications in the first 3 months and then at 12 months included the following: severe hemoptysis in 4 (3.5%) and 4 (3.5%) patients, pneumonia requiring hospitalization in 32 (28.1%) and 9 (7.9%) patients and pneumothorax in 7 (6.1%) and 2 (1.7%) patients, respectively. Milder adverse events included self-limited hemoptysis, pneumonias, or COPD exacerbations treated orally. Conclusion LVRC improved PFT, 6MWT and mMRC initially, but the

  19. The potential lymphangiogenic effects of hepatocyte growth factor/scatter factor in vitro and in vivo.

    PubMed

    Jiang, Wen G; Davies, Gaynor; Martin, Tracey A; Parr, Christian; Watkins, Gareth; Mansel, Robert E; Mason, Malcolm D

    2005-10-01

    Lymphangiogenesis is key to the lymphatic spread of cancer cells. The current study examined the potential effect of hepatocyte growth factor (HGF), a factor known to have strong biological effects on endothelial cells, on the lymphangiogenic function of endothelial cells and the formation of lymphatic vessels using both in vitro and in vivo models. Human endothelial cells that have lymphatic characteristics, human prostate and breast cancer cells PC-3 and MDA MB 231, were used. Expression of lymphatic markers, podoplanin, Prox-1, vascular endothelial growth factor receptor 3 (VEGF-R3) and LYVE-1 was determined using reverse transcription polymerase reaction and quantitative PCR. In nude mice prostate and breast xenograft tumour models, either HGF or an HGF-producing fibroblast cell line MRC-5 was given with or without the HGF antagonist, NK4. The lymphangiogenic marker and lymphatic vessels in tumour tissues were also assessed using quantitative PCR and immunohistochemistry, respectively. In the mice tumour models, infusion of rhHGF significantly increased the levels of podoplanin and LYVE-1 in the tumour (p=0.05 for podoplanin and p<0.05 for LYVE-1 vs. without HGF in the prostate tumour model, p<0.05 for podoplanin and p<0.01 for LYVE-1 vs. without HGF for the breast tumour model; p<0.05 for podoplanin and p<0.01 for LYVE-1 vs. without HGF in the breast tumour model). The increased level of LYVE-1 transcript was supported by an increase in the number of LYVE-1-positive lymphatic vessels in tumours, using immunohistochemical analysis. Co-injection of MRC5 cells also increased the levels of LYVE-1 and number of LYVE-1-positive vessels in tumour tissues. The effects of HGF and MRC5 were significantly reduced by the HGF antagonist, NK4. In the in vitro models, rhHGF significantly increased the level of both podoplanin and LYVE-1, as shown by quantitative PCR analysis. Hepatocyte growth factor has potential lymphangiogenic activities, and this may have important

  20. Overview of measles and mumps vaccine: origin, present, and future of vaccine production.

    PubMed

    Betáková, T; Svetlíková, D; Gocník, M

    2013-01-01

    Measles and mumps are common viral childhood diseases that can cause serious complications. Vaccination remains the most efficient way to control the spread of these viruses. The manufacturing capability for viral vaccines produced in embryonated hen eggs and conventional/classical cell substrates, such as chicken embryo fibroblast or primary dog kidney cell substrates, is no longer sufficient. This limitation can be overcome by utilizing other recognized cell substrates such as Madin Darby Canine Kidney (MDCK), Chinese Hamster Ovary (CHO), Vero (monkey origin) cells, MRC-5 (human diploid) or as an alternative, introducing new cell substrates of human or avian origin. A very important factor in vaccine production is the safety and immunogenicity of the final vaccine, where the proper choice of cell substrate used for virus propagation is made. All substrates used in vaccine production must be fully characterized to avoid the contamination of hidden unknown pathogens which is difficult to achieve in primary cell substrates.

  1. Spinal-cord syndrome due to non-compressive Paget's disease of bone: a spinal-artery steal phenomenon reversible with calcitonin.

    PubMed

    Herzberg, L; Bayliss, E

    1980-07-05

    A 76-year-old man had progressive low back pain, leg weakness, and sensory loss. Radiology showed changes consistent with wide-spread Paget's disease, but no cord compression or involvement of nerve roots was detected by myelography or computerised axial tomography. His symptoms were relieved within 12 days of starting 100 MRC units of subcutaneous salmon calcitonin and recurred when calcitonin was discontinued for 5 days. The improvement continued on calcitonin treatment for 1 year, with falls in serum alkaline phosphatase and urinary hydroxyproline excretion. It is suggested that calcitonin treatment, in reducing the abnormally high metabolic activity of the diseased bone, and hence its vascular perfusion, allows more blood to reach the spinal cord.

  2. Anticancer photodynamic therapy based on the use of a microsystem

    NASA Astrophysics Data System (ADS)

    Jastrzebska, E.; Bulka, N.; Zukowski, K.; Chudy, M.; Brzozka, Z.; Dybko, A.

    2015-07-01

    The paper presents the evaluation of photodynamic therapy (PDT) procedures with an application of a microsystem. Two cell lines were used in the experiments, i.e. human lung carcinoma - A549 and normal human fetal lung fibroblast MRC5. Mono-, coculture and mixed cultures were performed in a microsystem at the same time. The microsystem consisted of a concentration gradient generator (CGG) which generates different concentrations of a photosensitizer, and a set of microchambers for cells. The microchambers were linked by microchannels of various length in order to allow cells migration and in this way cocultures were created. Transparent materials were used for the chip manufacture, i.e. glass and poly(dimethylsiloxane). A high power LED was used to test photodynamic therapy effectiveness in the microsystem.

  3. Replication of Bovine Herpesvirus Type 4 in Human Cells In Vitro

    PubMed Central

    Egyed, László

    1998-01-01

    A reference strain (Movár 33/63) of bovine herpesvirus type 4 (BHV-4) was inoculated into 14 different human cell lines and five primary cell cultures representing various human tissues. BHV-4 replicated in two embryonic lung cell lines, MRC-5 and Wistar-38, and in a giant-cell glioblastoma cell culture. Cytopathic effect and intranuclear inclusion bodies were observed in these cells. PCR detected a 10,000-times-higher level of BHV-4 DNA. Titration of the supernatant indicated a 100-fold increase of infectious particles. Since this is the first bovine (human herpesvirus 8 and Epstein-Barr virus related) herpesvirus which replicates on human cells in vitro, the danger of possible human BHV-4 infection should not be ignored. PMID:9650976

  4. The true cost of precautionary chemicals regulation.

    PubMed

    Durodié, Bill

    2003-04-01

    This article explores the possible social costs of introducing an overly precautionary regulatory regime for chemicals It begins by examining research by the UK Medical Research Council Institute for Environment and Health (MRC-IEH), which suggests that the resource implications of the proposals contained in the European Commission White Paper "Strategy for a Future Chemicals Policy" are unrealistic and even unrealizable. The article then focuses on contemporary debates pertaining to endocrine disrupting chemicals (EDCs) and goes on to question whether a "right to know" is always necessarily a good thing, or whether in certain instances it can lead to a society that feels more sorry than safe. Finally, problems relating to the representation and inclusion of public values in decision-making processes are raised prior to concluding with a call for an ambitious orientation toward social change rather than a self-limiting obsession with safety.

  5. High redshift radio galaxies

    NASA Technical Reports Server (NTRS)

    Mccarthy, Patrick J.

    1993-01-01

    High redshift galaxies that host powerful radio sources are examined. An overview is presented of the content of radio surveys: 3CR and 3CRR, 4C and 4C/USS, B2/1 Jy, MG, MRC/1Jy, Parkes/PSR, B3, and ESO Key-Project. Narrow-line radio galaxies in the visible and UV, the source of ionization and excitation of the emission lines, emission-line luminosities, morphology of the line-emitting gas, physical properties and energetics, kinematics of the line-emitting gas, and implications from the emission lines are discussed. The morphologies and environments of the host galaxies, the alignment effect, and spectral energy distributions and ages are also examined.

  6. Investigating health information needs of community radio stations and applying the World Wide Web to disseminate audio products.

    PubMed

    Snyders, Janus; van Wyk, Elmarie; van Zyl, Hendra

    2010-01-01

    The Web and Media Technologies Platform (WMTP) of the South African Medical Research Council (MRC) conducted a pilot project amongst community radio stations in South Africa. Based on previous research done in Africa WMTP investigated the following research question: How reliable is the content of health information broadcast by community radio stations? The main objectives of the project were to determine the 1) intervals of health slots on community radio stations, 2) sources used by community radio stations for health slots, 3) type of audio products needed for health slots, and 4) to develop a user friendly Web site in response to the stations' needs for easy access to audio material on health information.

  7. Inhibition of ganciclovir-resistant human cytomegalovirus replication by Kampo (Japanese herbal medicine).

    PubMed

    Murayama, Tsugiya; Yamaguchi, Nobuo; Iwamoto, Kozo; Eizuru, Yoshito

    2006-01-01

    We examined the effect of Kampo on the replication of ganciclovir (GCV)-resistant human cytomegalovirus (HCMV) in the human embryonic fibroblast cell line MRC-5. Treatment of HCMV-infected cells with Sho-seiryu-to (SST; Xiao-Qing-Long-Tang in Chinese) resulted in the inhibition of viral replication without affecting the cell growth. SST treatment decreased the synthesis of viral DNA, but had no virucidal effect on cell-free HCMV. However, the inhibitory effect of SST on HCMV replication was ablated by anti-interferon-beta (IFN-beta) antibody suggesting that SST inhibits the replication of GCV-resistant HCMV through the induction of IFN-beta. These results suggest that SST is a novel compund with potential as an anti-HCMV.

  8. 3D confocal reconstruction of gene expression in mouse.

    PubMed

    Hecksher-Sørensen, J; Sharpe, J

    2001-01-01

    Three-dimensional computer reconstructions of gene expression data will become a valuable tool in biomedical research in the near future. However, at present the process of converting in situ expression data into 3D models is a highly specialized and time-consuming procedure. Here we present a method which allows rapid reconstruction of whole-mount in situ data from mouse embryos. Mid-gestation embryos were stained with the alkaline phosphotase substrate Fast Red, which can be detected using confocal laser scanning microscopy (CLSM), and cut into 70 microm sections. Each section was then scanned and digitally reconstructed. Using this method it took two days to section, digitize and reconstruct the full expression pattern of Shh in an E9.5 embryo (a 3D model of this embryo can be seen at genex.hgu.mrc.ac.uk). Additionally we demonstrate that this technique allows gene expression to be studied at the single cell level in intact tissue.

  9. Neuroticism and Extraversion in Youth Predict Mental Wellbeing and Life Satisfaction 40 Years Later.

    PubMed

    Gale, Catharine R; Booth, Tom; Mõttus, René; Kuh, Diana; Deary, Ian J

    2013-12-01

    Neuroticism and Extraversion are linked with current wellbeing, but it is unclear whether these traits in youth predict wellbeing decades later. We applied structural equation modelling to data from 4583 people from the MRC National Survey of Health and Development. We examined the effects of Neuroticism and Extraversion at ages 16 and 26 years on mental wellbeing and life satisfaction at age 60-64 and explored the mediating roles of psychological and physical health. Extraversion had direct, positive effects on both measures of wellbeing. The impact of Neuroticism on both wellbeing and life satisfaction was largely indirect through susceptibility to psychological distress and physical health problems. Personality dispositions in youth have enduring influence on wellbeing assessed about forty years later.

  10. Antimycobacterial, antimicrobial, and biocompatibility properties of para-aminosalicylic acid with zinc layered hydroxide and Zn/Al layered double hydroxide nanocomposites

    PubMed Central

    Saifullah, Bullo; El Zowalaty, Mohamed E; Arulselvan, Palanisamy; Fakurazi, Sharida; Webster, Thomas J; Geilich, Benjamin M; Hussein, Mohd Zobir

    2014-01-01

    The treatment of tuberculosis by chemotherapy is complicated due to multiple drug prescriptions, long treatment duration, and adverse side effects. We report here for the first time an in vitro therapeutic effect of nanocomposites based on para-aminosalicylic acid with zinc layered hydroxide (PAS-ZLH) and zinc-aluminum layered double hydroxides (PAS-Zn/Al LDH), against mycobacteria, Gram-positive bacteria, and Gram-negative bacteria. The nanocomposites demonstrated good antimycobacterial activity and were found to be effective in killing Gram-positive and Gram-negative bacteria. A biocompatibility study revealed good biocompatibility of the PAS-ZLH nanocomposites against normal human MRC-5 lung cells. The para-aminosalicylic acid loading was quantified with high-performance liquid chromatography analysis. In summary, the present preliminary in vitro studies are highly encouraging for further in vivo studies of PAS-ZLH and PAS-Zn/Al LDH nanocomposites to treat tuberculosis. PMID:25114509

  11. Control system design for nano-positioning using piezoelectric actuators

    NASA Astrophysics Data System (ADS)

    Shan, Jinjun; Liu, Yanfang; Gabbert, Ulrich; Cui, Naigang

    2016-02-01

    This paper presents a systematic control system design for nano-positioning of a piezoelectric actuator (PEA). PEAs exhibit hysteresis nonlinearity, which can dramatically limit the application and performance of linear feedback control theory. Thus the hysteresis is compensated for based on the Maxwell resistive capacitor (MRC) model first. Then a proportional plus integral (PI) controller and a proportional double integral plus lead compensation (PII&L) controller are designed for the hysteresis-compensated PEA to account for model uncertainty, disturbance, and noise. The robust stability of both controllers is proved. The effectiveness of the proposed control scheme is demonstrated experimentally. Both controllers achieve fast precise positioning. The 2% settling times for the PI controller and the PII&L controller are 1.5 ms and 4.7 ms, respectively. The positioning resolution is upto 1 nm for both controllers.

  12. Cytotoxic components of Pereskia bleo (Kunth) DC. (Cactaceae) leaves.

    PubMed

    Malek, Sri Nurestri Abdul; Shin, Sim Kae; Wahab, Norhanom Abdul; Yaacob, Hashim

    2009-05-06

    Dihydroactinidiolide (1) and a mixture of sterols [campesterol (2), stigmasterol (3) and beta-sitosterol (4)], together with the previously isolated individual compounds beta-sitosterol (4), 2,4-di-tert-butylphenol (5), alpha-tocopherol (6), phytol (7) were isolated from the active ethyl acetate fraction of Pereskia bleo (Kunth) DC. (Cactaceae) leaves. Cytotoxic activities of the above mentioned compounds against five human carcinoma cell lines, namely the human nasopharyngeal epidermoid carcinoma cell line (KB), human cervical carcinoma cell line (CasKi), human colon carcinoma cell line (HCT 116), human hormone-dependent breast carcinoma cell line (MCF7) and human lung carcinoma cell line (A549); and non-cancer human fibroblast cell line (MRC-5) were investigated. Compound 5 possessed very remarkable cytotoxic activity against KB cells, with an IC(50 )value of 0.81microg/mL. This is the first report on the cytotoxic activities of the compounds isolated from Pereskia bleo.

  13. Is there an optimum detector size for digital night vision goggles?

    NASA Astrophysics Data System (ADS)

    Holst, Gerald C.

    2016-05-01

    In previous studies maximum acquisition range was achieved when Fλ/d approached 2. There was no constraint on magnification or field-of-view. This suggested that detector size approach λ/2 when F = 1. Night vision goggles typically have a fixed FOV of 40 deg with unity magnification. Digital night vision goggles (DNVG) acquisition range is limited by the human visual system resolution of 0.291 mrad (20/20 vision). This suggests the maximum number of horizontal detectors should be about 2500 with a minimum pixel size of about 8 μm when F = 1 and aperture = 1 inch. Values change somewhat depending upon f-number and noise level. Ranges are provided for GaAs and InGaAs detectors under starlight conditions. The different spectral responses create minimum resolvable contrast (MRC) test issues.

  14. Factory acceptance test results for the DIRSP projection optics

    NASA Astrophysics Data System (ADS)

    Thomas, Matthew C.; Ward, Craig S.

    2000-07-01

    The Factory Acceptance Test (FAT) results for the projection optical subsystem (POS) of US Army STIRCOM's dynamic infrared scene projector (DIRSP) are presented in this paper. DIRSP is a low background (-35 degrees Celsius) hardware-in-the- loop (HWIL), long-wave infrared (LWIR) scene projector built by Mission Research Corporation (MRC) for use by the Redstone Technical Test Center (RTTC). It has an effective emitter array size of 1632 X 672 suspended-membrane micro-resistor elements. The POS is responsible for generating this effective array size from three smaller arrays using a mosaic image combiner, adding background light from an external blackbody, and collimating the combined radiation with a 5:1 vacuum enclosed -35 degree Celsius zoom lens. The FAT results reported demonstrate good POS performance compared to the design for focal length, F/#, MTF and apparent temperature.

  15. Walking the Talk: Adopting and Adapting Sustainable Scientific Software Development processes in a Small Biology Lab

    PubMed Central

    Crusoe, Michael R.; Brown, C. Titus

    2016-01-01

    The khmer software project provides both research and production functionality for largescale nucleic-acid sequence analysis. The software implements several novel data structures and algorithms that perform data pre-fltering for common bioinformatics tasks, including sequence mapping and de novo assembly. Development is driven by a small lab with one full-time developer (MRC), as well as several graduate students and a professor (CTB) who contribute regularly to research features. Here we describe our efforts to bring better design, testing, and more open development to the khmer software project as of version 1.1. The khmer software is developed openly at http://github.com/dib-lab/khmer/. PMID:27942385

  16. An outbreak of herpes rugbiorum managed by vaccination of players and sociosexual contacts.

    PubMed

    Skinner, G R; Davies, J; Ahmad, A; McLeish, P; Buchan, A

    1996-11-01

    An outbreak of herpes rugbiorum involved nine players including the scrum half and the full back. The infection was characterized by significant constitutional upset with decreased levels of general fitness and match performance for 1-4 months following the outbreak; one player had herpetic lesions on his right eyelid and corneum. Every infected player, 15 non-infected players and five sociosexual contacts received two vaccinations with intracellular subunit vaccine NFU. Ac. HSV-1 (S-MRC5). None of the players or contacts developed cutaneous herpetic recurrence during a follow-up period of 3 years; the player with ocular disease had one recurrence at 30 months following the original episode. These findings encourage consideration of prophylactic or post-exposure vaccination of participants in rugby or other contact sports with this or other appropriate herpes simplex vaccine.

  17. The cytotoxicity of 8-O-4' neolignans from the seeds of Crataegus pinnatifida.

    PubMed

    Huang, Xiao-Xiao; Zhou, Chen-Chen; Li, Ling-Zhi; Li, Fei-Fei; Lou, Li-Li; Li, Dian-Ming; Ikejima, Takshi; Peng, Ying; Song, Shao-Jiang

    2013-10-15

    Nine new 8-O-4' neolignans, named pinnatifidanin B I-IX (1-9), together with 9 known analogs (10-18) were isolated from the seeds of Crataegus pinnatifida. The structures of 1-18 were determined by spectroscopic methods, including 1D, 2D NMR, CD and HRESIMS analysis. Compounds 8-11, 17 and 18 displayed potent cytotoxic activities against human cancer cell lines, and most interestingly, none of the 6 compounds displayed inhibitory activity against human lung cell line (Mrc5). The 6 cytotoxic compounds are considered to be potential as antitumor agents, which could significantly inhibit the cancer cell growth in a dose-dependent manner and are probably safer than positive control drug.

  18. Hydrological regime of the Black Sea waters: numerical modeling

    NASA Astrophysics Data System (ADS)

    Gippius, F. N.; Arkhipkin, V. S.

    2012-04-01

    bottom temperature is nearly the same in all seasons - approximately 9,1 °C. The values of salinity at the sea surface are usually less near the coasts (16 - 17 ‰) than in the central areas of the sea (approximately 18 ‰) due to fresh water discharge and its further transportation by surface currents. A very strong surface salinity gradient is observed in May near the Danube estuary. The salinity values are growing with the depth. They reach their maximal values at the bottom of the sea - approximately 22,3 ‰. The most significant surface currents of the Black Sea are the cyclonic Main Rim Current (MRC) running along the continental slope, several quasi-cyclonic gyres inside the MRC and quasi-static anticyclonical eddies between the MRC and the shore. The MRC is most intense in spring, its velocities may reach 24 cm/s at that time.

  19. Final report on evaluation of cyclocraft support of oil and gas operations in wetland areas

    SciTech Connect

    Eggington, W.J.; Stevens, P.M.; John, C.J.; Harder, B.J.; Lindstedt, D.M.

    1994-10-01

    The cyclocraft is a proven hybrid aircraft, capable of VTOL, lifting heavy and bulky loads, highly controllable, having high safety characteristics and low operating costs. Mission Research Corporation (MRC), under Department of Energy sponsorship, is evaluating the potential use of cyclocraft in the transport of drill rigs, mud, pipes and other materials and equipment, in a cost effective and environmentally safe manner, to support oil and gas drilling, production, and transportation operations in wetland areas. Based upon the results of an earlier parametric study, a cyclocraft design, having a payload capacity of 45 tons and designated H.1 Cyclocraft, was selected for further study, including the preparation of a preliminary design and a development plan, and the determination of operating costs. This report contains all of the results derived from the program to evaluate the use of cyclocraft in the support of oil and gas drilling and production operations in wetland areas.

  20. Design, synthesis and antimycobacterial activities of 1-methyl-2-alkenyl-4(1H)-quinolones

    PubMed Central

    Wube, Abraham A.; Hüfner, Antje; Thomaschitz, Christina; Blunder, Martina; Kollroser, Manfred; Bauer, Rudolf; Bucar, Franz

    2011-01-01

    A series of 23 new 1-methyl-2-alkenyl-4(1H)quinolones have been synthesized and evaluated in vitro for their antimycobacterial activities against fast growing species of mycobacteria, such as Mycobacterium fortuitum, M. smegmatis and M. phlei. The compounds displayed good to excellent inhibition of the growth of the mycobacterial test strains with improved antimycobacterial activity compared to the hit compound, evocarpine. The most active compounds, which possessed chain length of 11–13 carbons at position-2 displayed potent inhibitory effects with an MIC value of 1.0 mg/L. In a human diploid embryonic lung cell line, MRC-5 cytotoxicity assay, the alkaloids showed weak to moderate cytotoxic activity. Biological evaluation of these evocarpine analogues on the less pathogenic fast growing strains of mycobacteria showed an interesting antimycobacterial profile and provided significant insight into the structure–activity relationships. PMID:21106378

  1. Educational Attainment and Women’s Environmental Mastery in Midlife

    PubMed Central

    Deeg, Dorly; Kuh, Diana

    2016-01-01

    Using data from 1,184 women in the MRC National Survey of Health and Development, we estimated associations between education and Ryff’s environmental mastery scale scores at age 52. Confirmatory factor analysis indicated two subscales, here termed mastery skills and mastery accomplishments. Low education was associated with higher mastery skills. This was partly explained by childhood socioeconomic position, as mastery was lower among those with fathers in the most and least advantaged occupational classes. Education was not associated with mastery accomplishments in unadjusted models. Lower ambitions for family/home were associated with higher mastery accomplishments and may have partly suppressed as an association between education and mastery accomplishments. This study highlights childhood as well as adult correlates of mastery and adds to mounting evidence that higher mastery is not universally found among those who are more educated. PMID:27048696

  2. Motor recovery and the breathing arm after brachial plexus surgical repairs, including re-implantation of avulsed spinal roots into the spinal cord.

    PubMed

    Htut, M; Misra, V P; Anand, P; Birch, R; Carlstedt, T

    2007-04-01

    Forty-four patients with severe traction brachial plexus avulsion injuries were studied following surgical repairs. In eight patients, re-implanting avulsed spinal roots directly to the spinal cord was performed with other repairs and motor recovery in the proximal limb was similar to that achieved by conventional nerve grafts and transfers when assessed using the MRC clinical grades, Narakas scores, EMG and Transcranial Magnetic Stimulation (TMS). Thirty-four of the 37 patients had co-contractions of agonist and antagonist muscle groups. Spontaneous contractions of limb muscles in synchrony with respiration, the "breathing arm", were noted in 26 of 37 patients: in three patients, the source of the breathing arm was from spinal cord re-connection, providing evidence of regeneration from the CNS to the periphery. Our study shows that re-connection of avulsed spinal roots can produce good motor recovery and provides a clinical model for developing new treatments which may enhance nerve regeneration.

  3. Synthesis of magnetic and fluorescent bifunctional nanocomposites and their applications in detection of lung cancer cells in humans.

    PubMed

    Ma, Jingwei; Fan, Qishi; Wang, Lianhui; Jia, Nengqin; Gu, Zhidong; Shen, Hebai

    2010-06-15

    We developed a novel strategy to detect lung cancer cells by utilizing magnetic and fluorescent bifunctional nanocomposites (BNPs) in combination with monoclonal anti-carcinoembryonic antigen (CEA) antibodies. The BNPs, consisting of silica-coated superparamagnetic nanoparticles and quantum dots (QDs), exhibited high luminescence and were easily separated in an external magnetic field. The binding specificity of the antibody-conjugated BNPs (immunonanoparticles) were confirmed via incubating with human lung adenocarcinoma SPCA-1 cells, human leukemic K562 cells and human embryonic lung fibroblasts MRC-5 cells. Further experiments demonstrated that the as-prepared immunonanoparticles can efficiently capture and detect cancer cells in pleural effusion from lung cancer patients. These results suggest that this method, of which the detection procedures are completed within 1h, could be applied to the rapid and cost-effective monitoring of cancer cells in clinical samples.

  4. The radio-radial nerve transfer for elbow extension restoration in C5 to C7 nerve root injury.

    PubMed

    Flores, Leandro Pretto

    2012-01-01

    Extension of the elbow is required to oppose gravity; however, activation of the triceps brachii is frequently underestimated during the surgical planning for brachial plexus injuries. This report aims to describe a novel technique of distal nerve transfer designed for elbow extension reconstruction in patients sustaining a C5-C7 nerve root injury. We report a patient sustaining a brachial plexus injury with triceps palsy and preserved finger extension motion; after careful intraneural dissection of the radial nerve, a fascicle innervating the extensor digitorum communis muscle was sectioned, derouted and connected to a motor branch to the lateral head of the triceps. Eleven months after surgery, elbow extension strength scored MRC M4. No deficits on finger extension were observed.

  5. Channel Characterization and Robust Tracking for Diversity Reception over Time-Variant Off-Body Wireless Communication Channels

    NASA Astrophysics Data System (ADS)

    Van Torre, Patrick; Vallozzi, Luigi; Rogier, Hendrik; Moeneclaey, Marc; Verhaevert, Jo

    2010-12-01

    In the 2.45 GHz band, indoor wireless off-body data communication by a moving person can be problematic due to time-variant signal fading and the consequent variation in channel parameters. Off-body communication specifically suffers from the combined effects of fading, shadowing, and path loss due to time-variant multipath propagation in combination with shadowing by the human body. Measurements are performed to analyze the autocorrelation, coherence time, and power spectral density for a person equipped with a wearable receive system moving at different speeds for different configurations and antenna positions. Diversity reception with multiple textile antennas integrated in the clothing provides a means of improving the reliability of the link. For the dynamic channel estimation, a scheme using hard decision feedback after MRC with adaptive low-pass filtering is demonstrated to be successful in providing robust data detection for long data bursts, in the presence of dramatic channel variation.

  6. Preparation and toxicological evaluation of methyl pyranoanthocyanin.

    PubMed

    Zhu, Zhenzhou; Wu, Nao; Kuang, Minjie; Lamikanra, Olusola; Liu, Gang; Li, Shuyi; He, Jingren

    2015-09-01

    Anthocyanins are increasingly valued in the food industry for their functional properties and as food colorants. The broadness of their applications has, however, been limited by the lack of stability of these natural pigment extracts in a number of food systems. The potential application of pyranoanthocyanins, anthocyanin derivatives with better stability conferred by the added pyran ring, as a food ingredient was determined. Methylpyranoanthocyanin (MPA) was prepared from reaction of acetone and anthocyanin extracts from red grapes. Reaction products were sequentially purified with polyamide resin, TSK gel resin and semi-preparative HPLC to a purity level >98%. Cytoprotective influence tests of the purified MPA indicated its significant protective effect against H2O2 induced MRC-5 cell damage. Results of evaluations of possible acute toxicity effects on MPA-fed mice, including macro and microscopic assessments, support the conclusion of a non-toxic effect of MPA, and its potential safe use as a food additive.

  7. Association of Biomarkers With Pre–Radiographically Defined and Radiographically Defined Knee Osteoarthritis in a Population-Based Study

    PubMed Central

    Cibere, Jolanda; Zhang, Hongbin; Garnero, Patrick; Poole, A. Robin; Lobanok, Tatiana; Saxne, Tore; Kraus, Virginia B.; Way, Amanda; Thorne, Anona; Wong, Hubert; Singer, Joel; Kopec, Jacek; Guermazi, Ali; Peterfy, Charles; Nicolaou, Savvakis; Munk, Peter L.; Esdaile, John M.

    2016-01-01

    Objective To evaluate 10 biomarkers in magnetic resonance imaging (MRI)–determined, pre–radiographically defined osteoarthritis (pre-ROA) and radiographically defined OA (ROA) in a population-based cohort of subjects with symptomatic knee pain. Methods Two hundred one white subjects with knee pain, ages 40–79 years, were classified into OA subgroups according to MRI-based cartilage (MRC) scores (range 0–4) and Kellgren/Lawrence (K/L) grades of radiographic severity (range 0–4): no OA (MRC score 0, K/L grade <2), pre-ROA (MRC score ≥1, K/L grade <2), or ROA (MRC score ≥1, K/L grade ≥2). Urine and serum samples were assessed for levels of the following biomarkers: urinary biomarkers C-telopeptide of type II collagen (uCTX-II), type II and types I and II collagen cleavage neoepitopes (uC2C and uC1,2C, respectively), and N-telopeptide of type I collagen, and serum biomarkers sC1,2C, sC2C, C-propeptide of type II procollagen (sCPII), chondroitin sulfate 846 epitope, cartilage oligomeric matrix protein, and hyaluronic acid. Multicategory logistic regression was performed to evaluate the association of OA subgroup with individual biomarker levels and biomarker ratios, adjusted for age, sex, and body mass index. Results The risk of ROA versus no OA increased with increasing levels of uCTX-II (odds ratio [OR] 3.12, 95% confidence interval [95% CI] 1.35–7.21), uC2C (OR 2.13, 95% CI 1.04–4.37), and uC1,2C (OR 2.07, 95% CI 1.06–4.04), and was reduced in association with high levels of sCPII (OR 0.53, 95% CI 0.30–0.94). The risk of pre-ROA versus no OA increased with increasing levels of uC2C (OR 2.06, 95% CI 1.05–4.01) and uC1,2C (OR 2.06, 95% CI 1.12–3.77). The ratios of type II collagen degradation markers to collagen synthesis markers were better than individual biomarkers at differentiating the OA subgroups, e.g., the ratio of [uCTXII][uC1,2C] to sCPII was associated with a risk of ROA versus no OA of 3.47 (95% CI 1.34–9.03) and a risk of pre

  8. Multifractality, imperfect scaling and hydrological properties of rainfall time series simulated by continuous universal multifractal and discrete random cascade models

    NASA Astrophysics Data System (ADS)

    Serinaldi, F.

    2010-12-01

    Discrete multiplicative random cascade (MRC) models were extensively studied and applied to disaggregate rainfall data, thanks to their formal simplicity and the small number of involved parameters. Focusing on temporal disaggregation, the rationale of these models is based on multiplying the value assumed by a physical attribute (e.g., rainfall intensity) at a given time scale L, by a suitable number b of random weights, to obtain b attribute values corresponding to statistically plausible observations at a smaller L/b time resolution. In the original formulation of the MRC models, the random weights were assumed to be independent and identically distributed. However, for several studies this hypothesis did not appear to be realistic for the observed rainfall series as the distribution of the weights was shown to depend on the space-time scale and rainfall intensity. Since these findings contrast with the scale invariance assumption behind the MRC models and impact on the applicability of these models, it is worth studying their nature. This study explores the possible presence of dependence of the parameters of two discrete MRC models on rainfall intensity and time scale, by analyzing point rainfall series with 5-min time resolution. Taking into account a discrete microcanonical (MC) model based on beta distribution and a discrete canonical beta-logstable (BLS), the analysis points out that the relations between the parameters and rainfall intensity across the time scales are detectable and can be modeled by a set of simple functions accounting for the parameter-rainfall intensity relationship, and another set describing the link between the parameters and the time scale. Therefore, MC and BLS models were modified to explicitly account for these relationships and compared with the continuous in scale universal multifractal (CUM) model, which is used as a physically based benchmark model. Monte Carlo simulations point out that the dependence of MC and BLS

  9. Cytotoxic withanolide constituents of Physalis longifolia.

    PubMed

    Zhang, Huaping; Samadi, Abbas K; Gallagher, Robert J; Araya, Juan J; Tong, Xiaoqin; Day, Victor W; Cohen, Mark S; Kindscher, Kelly; Gollapudi, Rao; Timmermann, Barbara N

    2011-12-27

    Fourteen new withanolides, 1-14, named withalongolides A-N, respectively, were isolated from the aerial parts of Physalis longifolia together with eight known compounds (15-22). The structures of compounds 1-14 were elucidated through spectroscopic techniques and chemical methods. In addition, the structures of withanolides 1, 2, 3, and 6 were confirmed by X-ray crystallographic analysis. Using a MTS viability assay, eight withanolides (1, 2, 3, 7, 8, 15, 16, and 19) and four acetylated derivatives (1a, 1b, 2a, and 2b) showed potent cytotoxicity against human head and neck squamous cell carcinoma (JMAR and MDA-1986), melanoma (B16F10 and SKMEL-28), and normal fetal fibroblast (MRC-5) cells with IC₅₀ values in the range between 0.067 and 9.3 μM.

  10. Biologically active vallesamine, strychnan, and rhazinilam alkaloids from Alstonia: Pneumatophorine, a nor-secovallesamine with unusual incorporation of a 3-ethylpyridine moiety.

    PubMed

    Lim, Jun-Lee; Sim, Kae-Shin; Yong, Kien-Thai; Loong, Bi-Juin; Ting, Kang-Nee; Lim, Siew-Huah; Low, Yun-Yee; Kam, Toh-Seok

    2015-09-01

    Four alkaloids comprising two vallesamine, one strychnan, and one pyranopyridine alkaloid, in addition to 32 other known alkaloids were isolated from two Malayan Alstonia species, Alstonia pneumatophora and Alstonia rostrata. The structures of these alkaloids were determined using NMR and MS analyses, and in one instance, confirmed by X-ray diffraction analysis. The nor-6,7-secovallesamine alkaloid, pneumatophorine, is notable for an unusual incorporation of a 3-ethylpyridine moiety in a monoterpenoid indole. The rhazinilam-type alkaloids (rhazinicine, nor-rhazinicine, rhazinal, and rhazinilam) showed strong cytotoxicity toward human KB, HCT-116, MDA-MB-231, and MRC-5 cells, while pneumatophorine, the uleine alkaloid undulifoline, and the strychnan alkaloids, N4-demethylalstogustine and echitamidine, induced concentration dependent relaxation in phenylephrine-precontracted rat aortic rings.

  11. The identification of rRNA maturation sites in the microsporidian Encephalitozoon cuniculi argues against the full excision of presumed ITS1 sequence.

    PubMed

    Peyretaillade, E; Peyret, P; Metenier, G; Vivares, C P; Prensier, G

    2001-01-01

    In Encephalitozoon cuniculi like in other microsporidia, the primary transcript for SSU and LSU rRNAs includes only one internal transcribed spacer (ITS1) which separates SSU rRNA from the 5.8S region associated with LSU rRNA. The extraction of total RNA from E. cuniculi-infected MRC5 cells using a hot phenol/chloroform procedure enabled us to perform primer extension and S1 nuclease protection experiments in the aim of identifying rRNA maturation sites. Our data support a simple processing (four cleavage sites) with elimination of only nine nucleotides between SSU and LSU rRNA regions. Most of the presumed ITS1 sequence characterized by strain-dependent polymorphism therefore remains linked to SSU rRNA 3' end. A new secondary structure for the sixth domain of E. cuniculi LSU rRNA is proposed following the identification of its 3' terminus.

  12. MIMO Free-Space Optical Communication Employing Subcarrier Intensity Modulation in Atmospheric Turbulence Channels

    NASA Astrophysics Data System (ADS)

    Ghassemlooy, Zabih; Popoola, Wasiu O.; Ahmadi, Vahid; Leitgeb, Erich

    In this paper, we analyse the error performance of transmitter/receiver array free-space optical (FSO) communication system employing binary phase shift keying (BPSK) subcarrier intensity modulation (SIM) in clear but turbulent atmospheric channel. Subcarrier modulation is employed to eliminate the need for adaptive threshold detector. Direct detection is employed at the receiver and each subcarrier is subsequently demodulated coherently. The effect of irradiance fading is mitigated with an array of lasers and photodetectors. The received signals are linearly combined using the optimal maximum ratio combining (MRC), the equal gain combining (EGC) and the selection combining (SelC). The bit error rate (BER) equations are derived considering additive white Gaussian noise and log normal intensity fluctuations. This work is part of the EU COST actions and EU projects.

  13. Aromatase inhibitory, radical scavenging, and antioxidant activities of depsidones and diaryl ethers from the endophytic fungus Corynespora cassiicola L36.

    PubMed

    Chomcheon, Porntep; Wiyakrutta, Suthep; Sriubolmas, Nongluksna; Ngamrojanavanich, Nattaya; Kengtong, Surapong; Mahidol, Chulabhorn; Ruchirawat, Somsak; Kittakoop, Prasat

    2009-02-01

    Isolation of a broth extract of the endophytic fungus Corynespora cassiicola L36 afforded three compounds, corynesidones A (1) and B (3), and corynether A (5), together with a known diaryl ether 7. Compounds 1, 3, 5, and 7 were relatively non-toxic against cancer cells, and inactive toward normal cell line, MRC-5. Corynesidone B (3) exhibited potent radical scavenging activity in the DPPH assay, whose activity was comparable to ascorbic acid. Based on the ORAC assay, compounds 1, 3, 5, and 7 showed potent antioxidant activity. However, the isolated natural substances and their methylated derivatives (1-8) neither inhibited superoxide anion radical formation in the XXO assay nor suppressed TPA-induced superoxide anion generation in HL-60 cell line. Corynesidone A (1) inhibited aromatase activity with an IC(50) value of 5.30 microM.

  14. Transient response of thyroidectomized pigs to bolus calcium injections and the effect of salmon calcitonin and parathyroid hormone.

    PubMed

    Jaros, G G; Van Hoorn-Hickman, R; Maier, H; Newman, E

    1983-04-01

    The intravenous injection of calcium gluconate (0.11 mM/kg body weight) into conscious thyroidectomized pigs elicits a 30% rise in both ionized and total calcium concentrations of plasma, which return to basal levels within 180 min. The administration of calcitonin (2.5-10 MRC U/kg body weight) reduces this time to 30 to 40 min which is similar to the time obtained in thyroid intact animals. These results suggest that calcitonin may be involved in the fast calcium removal processes and thus in the short-term regulating system of calcium homeostasis. Neither parathyroidectomy nor the administration of parathyroid hormone affected the time for recovery in thyroidectomized pigs, suggesting that the short-term regulation is independent on the parathyroid gland and its hormone.

  15. Pig calcitonin in the treatment of localised osteoporosis.

    PubMed

    De Bastiani, G; Nogarin, L; Perusi, M

    1976-08-01

    On the basis of positive results obtained in the treatment of Sudeck's atrophy with calcitonin, the authors extended their investigation to other forms of localised osteoporosis. Six patients were examined affected by osteoporosis secondary to immobilisation, three patients with osteoporosis of the lower limbs from paralysis of the sciatic nerve and six patients with migrant osteoporosis. Treatment was as follows: pig calcitonin (Calcitar) in doses of 160 u MRC/daily + calcium gluconate in doses of 3 gr/daily. The duration of treatment averaged forty five days. In osteoporosis from immobilisation and nerve lesions the calcitonin treatment did not influence the condition and there was no change in radiographic appearances nor was there any analgesic action. On the other hand, the results were clearly positive in migrant osteoporosis: in all the patients treated there was complete regression of pain, cutaneous trophic changes, and functional loss. At a later stage, normal radiographic appearances were restored.

  16. Marketing and clinical trials: a case study

    PubMed Central

    Francis, David; Roberts, Ian; Elbourne, Diana R; Shakur, Haleema; Knight, Rosemary C; Garcia, Jo; Snowdon, Claire; Entwistle, Vikki A; McDonald, Alison M; Grant, Adrian M; Campbell, Marion K

    2007-01-01

    Background Publicly funded clinical trials require a substantial commitment of time and money. To ensure that sufficient numbers of patients are recruited it is essential that they address important questions in a rigorous manner and are managed well, adopting effective marketing strategies. Methods Using methods of analysis drawn from management studies, this paper presents a structured assessment framework or reference model, derived from a case analysis of the MRC's CRASH trial, of 12 factors that may affect the success of the marketing and sales activities associated with clinical trials. Results The case study demonstrates that trials need various categories of people to buy in – hence, to be successful, trialists must embrace marketing strategies to some extent. Conclusion The performance of future clinical trials could be enhanced if trialists routinely considered these factors. PMID:18028537

  17. The 2009 Nobel Prize in Chemistry: Thomas A. Steitz and the Structure of the Ribosome

    PubMed Central

    Zhao, Peter

    2011-01-01

    Over the past 200 years, there have been countless groundbreaking discoveries in biology and medicine at Yale University. However, one particularly noteworthy discovery with profoundly important and broad consequences happened here in just the past two decades. In 2009, Thomas Steitz, the Sterling Professor of Molecular Biophysics & Biochemistry, was awarded the Nobel Prize in Chemistry for “studies of the structure and function of the ribosome,” along with Venkatraman Ramakrishnan of the MRC Laboratory of Molecular Biology and Ada E. Yonath of the Weizmann Institute of Science. This article covers the historical context of Steitz’s important discovery, the techniques his laboratory used to study the ribosome, and the impact that this research has had, and will have, on the future of biological and medical research. PMID:21698044

  18. Exploring Synthetic and Systems Biology at the University of Edinburgh.

    PubMed

    Fletcher, Liz; Rosser, Susan; Elfick, Alistair

    2016-06-15

    The Centre for Synthetic and Systems Biology ('SynthSys') was originally established in 2007 as the Centre for Integrative Systems Biology, funded by the Biotechnology and Biological Sciences Research Council (BBSRC) and the Engineering and Physical Sciences Research Council (EPSRC). Today, SynthSys embraces an extensive multidisciplinary community of more than 200 researchers from across the University with a common interest in synthetic and systems biology. Our research is broad and deep, addressing a diversity of scientific questions, with wide ranging impact. We bring together the power of synthetic biology and systems approaches to focus on three core thematic areas: industrial biotechnology, agriculture and the environment, and medicine and healthcare. In October 2015, we opened a newly refurbished building as a physical hub for our new U.K. Centre for Mammalian Synthetic Biology funded by the BBSRC/EPSRC/MRC as part of the U.K. Research Councils' Synthetic Biology for Growth programme.

  19. Regularization of inverse photomask synthesis to enhance manufacturability

    NASA Astrophysics Data System (ADS)

    Jia, Ningning; Wong, Alfred K.; Lam, Edmund Y.

    2009-12-01

    Mask manufacturability has been considered as a major issue in the adoption of inverse lithography (IL) in practice. With smaller technology nodes, IL distorts the mask pattern more aggressively. The distorted mask often contains curvilinear contour and irregular shapes, which cast a heavy computation burden on segmentation and data preparation. Total variation (TV) has been used for regularization in previous work, but it is not very effective in regulating the mask shape to be rectangular. In this paper, we apply TV regularization not only on the mask image but also on the mask edges, which forces the curves of edges to be more vertical or horizontal, because they give smaller TV values. Except for rectilinearity, a group of geometrical specifications of the mask pattern set by mask manufacture rule control (MRC) is also important for mask manufacturability. To prevent these characteristics from appearing, we also propose an intervention scheme into the optimization framework.

  20. Antiproliferative Activity of seco-Oxacassanes from Acacia schaffneri.

    PubMed

    Torres-Valencia, J Martín; Motilva, Virginia; Manríquez-Torres, J Jesús; García-Mauriño, Sofía; López-Lázaro, Miguel; Zbakh, Hanaa; Calderón-Montaño, José M; Gómez-Hurtado, Mario A; Gayosso-De-Lucio, Juan A; Cerda-García-Rojas, Carlos M; Joseph-Nathan, Pedro

    2015-06-01

    This work reports the antiproliferative activity of seco-oxacassanes 1-3, isolated from Acacia schaffneri, against human colon (HT-29), lung (A-549), and melanoma (UACC-62) cancer cell lines, as well as against their non-malignant counterparts CCD-841 CoN, MRC-5, and VH-10, respectively, using the sulforhodamine B test. While compounds 1 and 3 were inactive, 2 presented strong activity with IC50 values between 0.12 and 0.92 μg mL(-1). The cytotoxicity mechanisms of 2 were investigated by cell cycle analysis and through DNA repair pathways, indicating that the compound is capable of arresting the cell cycle in the G0/G1 phase. This effect might be generated through damage to DNA by alkylation. In addition, compound 2 was able to decrease HT-29 migration.

  1. Light-Weight Radioisotope Heater Unit final safety analysis report (LWRHU-FSAR): Volume 1: A. Introduction and executive summary: B. Reference Design Document (RDD)

    SciTech Connect

    Johnson, E.W.

    1988-10-01

    The orbiter and probe portions of the National Aeronautics and Space Administration (NASA) Galileo spacecraft contain components which require auxiliary heat during the mission. To meet these needs, the Department of Energy's (DOE's) Office of Special Applications (OSA) has sponsored the design, fabrication, and testing of a one-watt encapsulated plutonium dioxide-fueled thermal heater named the Light-Weight Radioisotope Heater Unit (LWRHU). This report, prepared by Monsanto Research Corporation (MRC), addresses the radiological risks which might be encountered by people both at the launch area and worldwide should postulated mission failures or malfunctions occur, resulting in the release of the LWRHUs to the environment. Included are data from the design, mission descriptions, postulated accidents with their consequences, test data, and the derived source terms and personnel exposures for the various events. 11 refs., 44 figs., 11 tabs.

  2. Cell scientist to watch - Madeline Lancaster.

    PubMed

    2017-01-01

    Madeline Lancaster received her first degree in biochemistry from the Occidental College in Los Angeles, California, and continued to follow her interests by pursuing a PhD in biomedical sciences in the laboratory of Joseph Gleeson at University of California, San Diego. She then left the USA to train as a postdoctoral fellow with Jürgen Knoblich at the Institute of Molecular Biotechnology of the Austrian Academy of Sciences in Vienna. Madeline was a recipient of the EMBO, Helen Hay Whitney and Marie Curie Incoming Fellowships, and in 2014 her work was recognised when she was awarded the Eppendorf Award for Young Investigators. She started her own lab at the MRC Laboratory for Molecular Biology in Cambridge, UK in 2015 and her group uses brain organoids to unravel the general principles of brain evolution, focusing on human brain development, as well as studying neurological diseases that involve defects in brain size.

  3. [Radiation Tolerant Electronics

    NASA Technical Reports Server (NTRS)

    1996-01-01

    Research work in the providing radiation tolerant electronics to NASA and the commercial sector is reported herein. There are four major sections to this report: (1) Special purpose VLSI technology section discusses the status of the VLSI projects as well as the new background technologies that have been developed; (2) Lossless data compression results provide the background and direction of new data compression pursued under this grant; (3) Commercial technology transfer presents an itemization of the commercial technology transfer; and (4) Delivery of VLSI to the Government is a solution and progress report that shows how the Government and Government contractors are gaining access to the technology that has been developed by the MRC.

  4. Neuroticism and Extraversion in Youth Predict Mental Wellbeing and Life Satisfaction 40 Years Later

    PubMed Central

    Gale, Catharine R; Booth, Tom; Mõttus, René; Kuh, Diana; Deary, Ian J

    2014-01-01

    Neuroticism and Extraversion are linked with current wellbeing, but it is unclear whether these traits in youth predict wellbeing decades later. We applied structural equation modelling to data from 4583 people from the MRC National Survey of Health and Development. We examined the effects of Neuroticism and Extraversion at ages 16 and 26 years on mental wellbeing and life satisfaction at age 60-64 and explored the mediating roles of psychological and physical health. Extraversion had direct, positive effects on both measures of wellbeing. The impact of Neuroticism on both wellbeing and life satisfaction was largely indirect through susceptibility to psychological distress and physical health problems. Personality dispositions in youth have enduring influence on wellbeing assessed about forty years later. PMID:24563560

  5. High-performance 512 x 512 scene projector for targets against space backgrounds

    NASA Astrophysics Data System (ADS)

    Cole, Barry E.; Han, Chien-Jih; Higashi, Robert E.; Pritchett, Donald G.; Sawyer, B.; Old, Thomas E.; Goldsmith, George C., II; Edwards, David G.; Stockbridge, Robert G.; Jones, Lawrence E.

    1994-06-01

    Honeywell and MRC have been developing a range of thermal scene projector arrays through the Wright Laboratory Armament Directorate's cryovacuum resistive infrared scene projector (CRISP) program and the Defense Nuclear Agency's nuclear optical dynamic display system (NODDS) program. The resistive emitters are fabricated on silicon nitride structures on pitches as small as 2 mils. These structures have low thermal mass, low thermal conductance, and high fill factor. Monolithic address and pixel storage electronics provide flicker-free operation of large arrays at high frame rates. The emitters have demonstrated > 600 K blackbody temperatures, high radiance, and > 103 dynamic range at very low power when operated at 40 K temperatures to achieve low background. This paper describes the performance of a CRISP 512 X 512 array consisting of 3.5 mil pixels and a high-speed 128 X 128 NODDS array consisting of ultra-low-power emitters.

  6. Clinical assessment tests in evaluating patients with chronic obstructive pulmonary disease

    PubMed Central

    Chuang, Ming-Lung; Lin, I-Feng; Lee, Chai-Yuan

    2016-01-01

    Abstract Exertional dyspnea scales (EDS) and health-related quality-of-life questionnaires (HRQoLQs) are used to assess chronic obstructive pulmonary disease (COPD). The GOLD guidelines categorize patients according to either 1 of these 2 domains, the lung function and the frequency of acute exacerbations in the preceding year, however with inconsistent results. Combining EDS and HRQoLQs may yield better results; however, the best combination is unclear. Whether the EDS quantifies the exercise capacity or the dyspnea perception is also unclear. The study was designed to correlate the EDS with exercise capacity and dyspnea perception and to evaluate the best combination of the EDS and HRQoLQ. Three EDS were compared by exercise capacity and Borg scores at rest and during exercise in 57 patients with COPD. Three HRQoLQs were compared by 4 domains of clinical assessments, and 2 types of exercise. The strength of correlation |r| was categorized by quartiles from <0.3 to ≥0.6. The EDS was better correlated with exercise capacities (|r| = 0.29–0.65, P < 0.05–<0.0001) than with the resting and exertional Borg scores (|r| = 0.08–0.55, P = NS- <0.0001). The EDS were moderately to strongly interrelated, but this correlation was weaker when including Oxygen-cost Diagram (OCD) (with the modified Medical Research Council, mMRC r = −0.56, with the baseline dyspnea index, BDI r = 0.49 vs. mMRC with BDI r = −0.73); however, the OCD had the strongest correlation with walking distance (r = 0.65, vs mMRC r = −0.59, BDI r = 0.5) and peak oxygen uptake (r = 0.39 vs mMRC r = −0.29, BDI r = 0.36). Among the HRQoLQs, the COPD assessment test (CAT) was most strongly correlated with the St. George Respiratory Questionnaire (SGRQ) (r = 0.77) and similar to the SGRQ regarding significant correlations with the other instruments (|r| = 0.29–0.67 vs. 0.36–0.77) but poorly with walking distance (r = −0.02). The

  7. Development of subunit preparations of cytomegalovirus antigen by aqueous extraction for immunization against cytomegalovirus infection.

    PubMed

    Billstrom, M A; Davies, J A; Buchan, A; Skinner, G R

    1993-01-01

    This study has examined different methods of preparation of a subunit vaccine from cytomegalovirus (CMV)-infected MRC cells in terms of protein and DNA content, antigenicity and immunogenicity. Two preparations have been developed where CMV proteins were obtained by extraction of infected cells with water. Virus particles were removed from the preparations by ultracentrifugation and residual virus was inactivated by formaldehyde in the WUF preparations or by chloroform in the WUCh preparations. The preparations contained CMV proteins which may play a role in protective immune responses, and the preparations were antigenic as determined by immunodiffusion, ELISA and immunoblotting. Immunogenicity as evaluated in rabbits indicated that the preparations stimulated neutralizing and immunoprecipitating antibody. These results suggest that the gentle method of water extraction of viral antigens may be a useful protocol for vaccine preparation.

  8. Characterization and immunogenicity of a candidate subunit vaccine against varicella-zoster virus.

    PubMed

    Davies, J; Hallworth, J A; McLeish, P; Randall, S; Martin, B A; Buchan, A; Skinner, G R

    1994-05-01

    This study describes the properties of an inactivated subunit antigen preparation from varicella-zoster virus (VZV)-infected MRC-5 cells by treatment with detergent and formaldehyde, ultracentrifugation over sucrose and acetone precipitation. The method preserved the antigenicity of VZV proteins and several VZV-specific glycoproteins, while virus DNA was less than 20 pg/250 micrograms protein--a putative vaccine dose. The vaccine was immunogenic in rabbits and stimulated antibodies to the major capsid protein as well as to glycoproteins; an immunoprecipitin was shared with a known immune human serum. The preparation contained no infectious VZV with no evidence of side effects in a rabbit or in five human vaccinees during a follow-up period of 6-10 years.

  9. Report of twelve years experience in open study of Skinner herpes simplex vaccine towards prevention of herpes genitalis.

    PubMed

    Skinner, G R; Fink, C; Melling, J; Wiblin, C; Thornton, B; Hallworth, J; Gardner, W; McLeish, P; Hartley, C; Buchan, A

    1992-01-01

    Three hundred and forty-seven subjects at risk for herpes genitalis were vaccinated with Skinner vaccine, NFUAc.HSV1.(S-MRC5), and were followed for an average duration of 2 years representing a total consortship of 664.4 years. Based on survey information obtained during this consortship, there were estimated to be 3076 recurrences which summated to 3.5 years total duration of disease and comprised at least 6794 lesions; there were an estimated 51997 episodes of intercourse including at least 241 episodes of unprotected intercourse in the presence of herpetic lesions. The rate of contraction of herpes genitalis was 6 of 54 consorts (11.1%) who received one vaccination and 7 of 293 (2.4%) who received two, three of four vaccinations. There was no evidence of physical or psychological side effects from vaccination.

  10. [Scores and stages in pneumology].

    PubMed

    Kuhn, Max

    2013-10-01

    Useful scales and classifications for patients with pulmonary diseases are discussed. The modified Medical Research Council breathlessness scale (mMRC) is a measure of disability in lung patients. The GOLD classifications, the COPD-Assessment Test (CAT) and the BODE Index are important to classify the severity of COPD and to measure the disability of these patients. The Geneva score is a clinical prediction rule used in determining the pre-test probability of pulmonary embolism. The Pulmonary Embolism Severity Index (PESI) is a scoring system used to predict 30 day mortality in patients with pulmonary embolism. The Epworth Sleepiness Scale is intended to measure daytime sleepiness in patients with sleep apnea syndrome. The Asthma Controll Test (ACT) determines if asthma symptoms are well controlled.

  11. Cell scientist to watch--Melina Schuh.

    PubMed

    Schuh, Melina; Bobrowska, Anna

    2016-01-01

    Melina Schuh received her diploma degree in biochemistry from the University of Bayreuth, Germany, where she completed her Diploma thesis with Stefan Heidmann and Christian Lehner. She went on to do her PhD with Jan Ellenberg at the European Molecular Biology Laboratory in Heidelberg, Germany. In 2009, after a bridging postdoc with Jan, Melina started her own group at the MRC Laboratory of Molecular Biology in Cambridge, UK. Since January 2016, she is a Director at the Max Planck Institute for Biophysical Chemistry in Göttingen, Germany, and will establish a new department focussing on meiosis. She is an EMBO Young Investigator and a recipient of the 2014 Lister Institute Research Prize, the 2014 Biochemical Society Early Career Award and the 2015 John Kendrew Young Scientist Award. Her lab is studying meiosis in mammalian oocytes, including human oocytes.

  12. GSE for Balloon-Borne I.M.S.: Decommutator and D/A Units,

    DTIC Science & Technology

    1982-10-01

    UNLSSFEhEEEEE8-09 F968-hh I FG /6 EhhhLINhmm 11111 I1111115~ 111WERE~ AFGL-TR-83-0095 GSE FOR BALLOON-BORNE I.M.S.: S DECOMMUTATOR AND D/A UNITS Raimundas Sukys ...R. Sukys J.S. Rochefort F19628-81-C-0162 9. PCRFO mr,,C OmG&Nkz&TIO NAb4E AND ADDR.S 0. P33IA. (L.1 E NT. V’,-o3= l. TASK No rtheaste rn Unive rs... Sukys , Steven Goldberq, Contrl,- Cir-cjits for Pocket Pa.l ac Neutra ization EprriiTlent and C’ther -, .ics , Scientific Report 1o. trw n Frtract E1 62

  13. An integrated PIN-array receiver for visible light communication

    NASA Astrophysics Data System (ADS)

    Li, Jie-Hui; Huang, Xing-Xing; Ji, Xin-Ming; Chi, Nan; Shi, Jian-Yang

    2015-10-01

    This paper first designs and demonstrates an integrated receiver for a visible light communication (VLC) system based on RGB LED and an array of silicon PIN diode detectors. The system uses a maximal ratio combining (MRC) algorithm to enhance system performance. The novel integrated PIN diode array design yields a high date rate of 1.2 Gbit s-1 by 16QAM-OFDM based on a commercially available RGB LED in a VLC system with bit error rate under a 7% pre-forward-error-correction (FEC) threshold of 3.8 × 10-3 after 30 cm free-space transmission. The results show that the use of integrated antennas in VLC systems will become a trend in the future.

  14. Cdc14B depletion leads to centriole amplification and its overexpression prevents unscheduled centriole duplication

    SciTech Connect

    Wu, Jun; Plumley, Hyekyung; Rhee, David; Johnson, Dabney K; Dunlap, John; Liu, Yie; Wang, Yisong

    2008-01-01

    Centrosome duplication is tightly controlled in coordination with DNA replication. The molecular mechanism of centrosome duplication remains unclear. Previous studies found that a fraction of human proline-directed phosphatase Cdc14B associates with centrosomes. However, Cdc14B's involvement in centrosome cycle control has never been explored. Here, we show that depletion of Cdc14B by RNA interference leads to centriole amplification in both HeLa and normal human fibroblast BJ and MRC-5 cells. Induction of Cdc14B expression through a regulatable promoter significantly attenuates centriole amplification in prolonged S-phase arrested cells and proteasome inhibitor Z-L3VS-treated cells. This inhibitory function requires centriole-associated Cdc14B catalytic activity. Together, these results suggest a potential function for Cdc14B phosphatase in maintaining the fidelity of centrosome duplication cycle.

  15. Revisiting Previously Investigated Plants: A Molecular Networking-Based Study of Geissospermum laeve.

    PubMed

    Fox Ramos, Alexander E; Alcover, Charlotte; Evanno, Laurent; Maciuk, Alexandre; Litaudon, Marc; Duplais, Christophe; Bernadat, Guillaume; Gallard, Jean-François; Jullian, Jean-Christophe; Mouray, Elisabeth; Grellier, Philippe; Loiseau, Philippe M; Pomel, Sébastien; Poupon, Erwan; Champy, Pierre; Beniddir, Mehdi A

    2017-03-10

    Three new monoterpene indole alkaloids (1-3) have been isolated from the bark of Geissospermum laeve, together with the known alkaloids (-)-leuconolam (4), geissolosimine (5), and geissospermine (6). The structures of 1-3 were elucidated by analysis of their HRMS and NMR spectroscopic data. The absolute configuration of geissolaevine (1) was deduced from the comparison of experimental and theoretically calculated ECD spectra. The isolation workflow was guided by a molecular networking-based dereplication strategy using an in-house database of monoterpene indole alkaloids. In addition, five known compounds previously undescribed in the Geissospermum genus were dereplicated from the G. laeve alkaloid extract network and were assigned with various levels of identification confidence. The antiparasitic activities against Plasmodium falciparum and Leishmania donovani as well as the cytotoxic activity against the MRC-5 cell line were determined for compounds 1-5.

  16. Genetic subpopulations of Rift Valley fever virus strains ZH548 and MP-12 and recombinant MP-12 strains.

    PubMed

    Lokugamage, Nandadeva; Freiberg, Alexander N; Morrill, John C; Ikegami, Tetsuro

    2012-12-01

    Rift Valley fever virus strain MP-12 was generated by serial plaque passages of parental strain ZH548 12 times in MRC-5 cells in the presence of a chemical mutagen, 5-fluorouracil. As a result, MP-12 encoded 4, 9, and 10 mutations in the S, M, and L segments, respectively. Among them, mutations in the M and L segments were responsible for attenuation, while the MP-12 S segment still encoded a virulent phenotype. We performed high-throughput sequencing of MP-12 vaccine, ZH548, and recombinant MP-12 (rMP-12) viruses. We found that rMP-12 contains very low numbers of viral subpopulations, while MP-12 and ZH548 contain 2 to 4 times more viral genetic subpopulations than rMP-12. MP-12 genetic subpopulations did not encode the ZH548 sequence at the 23 MP-12 consensus mutations. On the other hand, 4 and 2 mutations in M and L segments of MP-12 were found in ZH548 subpopulations. Thus, those 6 mutations were no longer MP-12-specific mutations. ZH548 encoded several unique mutations compared to other Egyptian strains, i.e., strains ZH501, ZH1776, and ZS6365. ZH548 subpopulations shared nucleotides at the mutation site common with those in the Egyptian strains, while MP-12 subpopulations did not share those nucleotides. Thus, MP-12 retains unique genetic subpopulations and has no evidence of reversion to the ZH548 sequence in the subpopulations. This study provides the first information regarding the genetic subpopulations of RVFV and shows the genetic stability of the MP-12 vaccine manufactured in MRC-5 cells.

  17. Genetic Subpopulations of Rift Valley Fever Virus Strains ZH548 and MP-12 and Recombinant MP-12 Strains

    PubMed Central

    Lokugamage, Nandadeva; Freiberg, Alexander N.; Morrill, John C.

    2012-01-01

    Rift Valley fever virus strain MP-12 was generated by serial plaque passages of parental strain ZH548 12 times in MRC-5 cells in the presence of a chemical mutagen, 5-fluorouracil. As a result, MP-12 encoded 4, 9, and 10 mutations in the S, M, and L segments, respectively. Among them, mutations in the M and L segments were responsible for attenuation, while the MP-12 S segment still encoded a virulent phenotype. We performed high-throughput sequencing of MP-12 vaccine, ZH548, and recombinant MP-12 (rMP-12) viruses. We found that rMP-12 contains very low numbers of viral subpopulations, while MP-12 and ZH548 contain 2 to 4 times more viral genetic subpopulations than rMP-12. MP-12 genetic subpopulations did not encode the ZH548 sequence at the 23 MP-12 consensus mutations. On the other hand, 4 and 2 mutations in M and L segments of MP-12 were found in ZH548 subpopulations. Thus, those 6 mutations were no longer MP-12-specific mutations. ZH548 encoded several unique mutations compared to other Egyptian strains, i.e., strains ZH501, ZH1776, and ZS6365. ZH548 subpopulations shared nucleotides at the mutation site common with those in the Egyptian strains, while MP-12 subpopulations did not share those nucleotides. Thus, MP-12 retains unique genetic subpopulations and has no evidence of reversion to the ZH548 sequence in the subpopulations. This study provides the first information regarding the genetic subpopulations of RVFV and shows the genetic stability of the MP-12 vaccine manufactured in MRC-5 cells. PMID:23035230

  18. A CO-rich merger shaping a powerful and hyperluminous infrared radio galaxy at z = 2: the Dragonfly Galaxy

    NASA Astrophysics Data System (ADS)

    Emonts, B. H. C.; Mao, M. Y.; Stroe, A.; Pentericci, L.; Villar-Martín, M.; Norris, R. P.; Miley, G.; De Breuck, C.; van Moorsel, G. A.; Lehnert, M. D.; Carilli, C. L.; Röttgering, H. J. A.; Seymour, N.; Sadler, E. M.; Ekers, R. D.; Drouart, G.; Feain, I.; Colina, L.; Stevens, J.; Holt, J.

    2015-07-01

    In the low-redshift Universe, the most powerful radio sources are often associated with gas-rich galaxy mergers or interactions. We here present evidence for an advanced, gas-rich (`wet') merger associated with a powerful radio galaxy at a redshift of z ˜ 2. This radio galaxy, MRC 0152-209, is the most infrared-luminous high-redshift radio galaxy known in the Southern hemisphere. Using the Australia Telescope Compact Array, we obtained high-resolution CO(1-0) data of cold molecular gas, which we complement with Hubble Space Telescope (HST)/Wide Field Planetary Camera 2 (WFPC2) imaging and William Herschel Telescope long-slit spectroscopy. We find that, while roughly MH2 ˜ 2 × 1010 M⊙ of molecular gas coincides with the central host galaxy, another MH2 ˜ 3 × 1010 M⊙ is spread across a total extent of ˜60 kpc. Most of this widespread CO(1-0) appears to follow prominent tidal features visible in the rest-frame near-UV HST/WFPC2 imaging. Lyα emission shows an excess over He II, but a deficiency over LIR, which is likely the result of photoionization by enhanced but very obscured star formation that was triggered by the merger. In terms of feedback, the radio source is aligned with widespread CO(1-0) emission, which suggests that there is a physical link between the propagating radio jets and the presence of cold molecular gas on scales of the galaxy's halo. Its optical appearance, combined with the transformational stage at which we witness the evolution of MRC 0152-209, leads us to adopt the name `Dragonfly Galaxy'.

  19. Two-dimensional homography-based correction of positional errors in widefield MRT images

    NASA Astrophysics Data System (ADS)

    Nayak, Arvind; Daiboo, Soobash; Shankar, N. Udaya

    2010-10-01

    A steradian of the southern sky has been imaged at 151.5 MHz using the Mauritius Radio Telescope (MRT). These images show systematics in the positional errors of sources when compared to source positions in the Molonglo Reference Catalogue (MRC). We have applied two-dimensional homography to correct for systematic positional errors in the image domain and thereby avoid re-processing the visibility data. Positions of bright (above 15σ) point sources, common to the MRT catalogue and MRC, are used to set up an over-determined system to solve for the homography matrix. After correction, the errors are found to be within 10 per cent of the beamwidth for these bright sources and the systematics are eliminated from the images. This technique will be of relevance to the new generation radio telescopes where, owing to huge data rates, only images after a certain integration would be recorded as opposed to raw visibilities. It is also interesting to note how our investigations cued to possible errors in the array geometry. The analysis of positional errors of sources showed that MRT images are stretched in declination by ~1 part in 1000. This translates to compression of the baseline scale in the visibility domain. The array geometry was re-estimated using the astrometry principle. The estimates show an error of ~1 mmm-1, which results in an error of about half a wavelength at 150 MHz for a 1-km north-south baseline. The estimates also indicate that the east-west arm is inclined by an angle of ~40 arcsec to the true east-west direction.

  20. Whole genome detection of rotavirus mixed infections in human, porcine and bovine samples co-infected with various rotavirus strains collected from sub-Saharan Africa

    PubMed Central

    Nyaga, Martin M.; Jere, Khuzwayo C.; Esona, Mathew D.; Seheri, Mapaseka L.; Stucker, Karla M.; Halpin, Rebecca A.; Akopov, Asmik; Stockwell, Timothy B.; Peenze, Ina; Diop, Amadou; Ndiaye, Kader; Boula, Angeline; Maphalala, Gugu; Berejena, Chipo; Mwenda, Jason M.; Steele, A. Duncan; Wentworth, David E.; Mphahlele, M. Jeffrey

    2015-01-01

    Group A rotaviruses (RVA) are among the main global causes of severe diarrhea in children under the age of 5 years. Strain diversity, mixed infections and untypeable RVA strains are frequently reported in Africa. We analysed rotavirus-positive human stool samples (n=13) obtained from hospitalised children under the age of 5 years who presented with acute gastroenteritis at sentinel hospital sites in six African countries, as well as bovine and porcine stool samples (n=1 each), to gain insights into rotavirus diversity and evolution. Polyacrylamide gel electrophoresis (PAGE) analysis and genotyping with G- (VP7) and P-specific (VP4) typing primers suggested that 13 of the 15 samples contained more than 11 segments and/or mixed G/P genotypes. Full-length amplicons for each segment were generated using RVA-specific primers and sequenced using the Ion Torrent and/or Illumina MiSeq next-generation sequencing platforms. Sequencing detected at least one segment in each sample for which duplicate sequences, often having distinct genotypes, existed. This supported and extended the PAGE and RT-PCR genotyping findings that suggested these samples were collected from individuals that had mixed rotavirus infections. The study reports the first porcine (MRC-DPRU1567) and bovine (MRC-DPRU3010) mixed infections. We also report a unique genome segment 9 (VP7), whose G9 genotype belongs to lineage VI and clusters with porcine reference strains. Previously, African G9 strains have all been in lineage III. Furthermore, additional RVA segments isolated from humans have a clear evolutionary relationship with porcine, bovine and ovine rotavirus sequences, indicating relatively recent interspecies transmission and reassortment. Thus, multiple RVA strains from sub-Saharan Africa are infecting mammalian hosts with unpredictable variations in their gene segment combinations. Whole-genome sequence analyses of mixed RVA strains underscore the considerable diversity of rotavirus sequences and

  1. Whole genome detection of rotavirus mixed infections in human, porcine and bovine samples co-infected with various rotavirus strains collected from sub-Saharan Africa.

    PubMed

    Nyaga, Martin M; Jere, Khuzwayo C; Esona, Mathew D; Seheri, Mapaseka L; Stucker, Karla M; Halpin, Rebecca A; Akopov, Asmik; Stockwell, Timothy B; Peenze, Ina; Diop, Amadou; Ndiaye, Kader; Boula, Angeline; Maphalala, Gugu; Berejena, Chipo; Mwenda, Jason M; Steele, A Duncan; Wentworth, David E; Mphahlele, M Jeffrey

    2015-04-01

    Group A rotaviruses (RVA) are among the main global causes of severe diarrhea in children under the age of 5years. Strain diversity, mixed infections and untypeable RVA strains are frequently reported in Africa. We analysed rotavirus-positive human stool samples (n=13) obtained from hospitalised children under the age of 5years who presented with acute gastroenteritis at sentinel hospital sites in six African countries, as well as bovine and porcine stool samples (n=1 each), to gain insights into rotavirus diversity and evolution. Polyacrylamide gel electrophoresis (PAGE) analysis and genotyping with G-(VP7) and P-specific (VP4) typing primers suggested that 13 of the 15 samples contained more than 11 segments and/or mixed G/P genotypes. Full-length amplicons for each segment were generated using RVA-specific primers and sequenced using the Ion Torrent and/or Illumina MiSeq next-generation sequencing platforms. Sequencing detected at least one segment in each sample for which duplicate sequences, often having distinct genotypes, existed. This supported and extended the PAGE and RT-PCR genotyping findings that suggested these samples were collected from individuals that had mixed rotavirus infections. The study reports the first porcine (MRC-DPRU1567) and bovine (MRC-DPRU3010) mixed infections. We also report a unique genome segment 9 (VP7), whose G9 genotype belongs to lineage VI and clusters with porcine reference strains. Previously, African G9 strains have all been in lineage III. Furthermore, additional RVA segments isolated from humans have a clear evolutionary relationship with porcine, bovine and ovine rotavirus sequences, indicating relatively recent interspecies transmission and reassortment. Thus, multiple RVA strains from sub-Saharan Africa are infecting mammalian hosts with unpredictable variations in their gene segment combinations. Whole-genome sequence analyses of mixed RVA strains underscore the considerable diversity of rotavirus sequences and

  2. The Toll-Like Receptor 5 Agonist Entolimod Mitigates Lethal Acute Radiation Syndrome in Non-Human Primates

    PubMed Central

    Krivokrysenko, Vadim I.; Toshkov, Ilia A.; Gleiberman, Anatoli S.; Krasnov, Peter; Shyshynova, Inna; Bespalov, Ivan; Maitra, Ratan K.; Narizhneva, Natalya V.; Singh, Vijay K.; Whitnall, Mark H.; Purmal, Andrei A.; Shakhov, Alexander N.; Gudkov, Andrei V.; Feinstein, Elena

    2015-01-01

    There are currently no approved medical radiation countermeasures (MRC) to reduce the lethality of high-dose total body ionizing irradiation expected in nuclear emergencies. An ideal MRC would be effective even when administered well after radiation exposure and would counteract the effects of irradiation on the hematopoietic system and gastrointestinal tract that contribute to its lethality. Entolimod is a Toll-like receptor 5 agonist with demonstrated radioprotective/mitigative activity in rodents and radioprotective activity in non-human primates. Here, we report data from several exploratory studies conducted in lethally irradiated non-human primates (rhesus macaques) treated with a single intramuscular injection of entolimod (in the absence of intensive individualized supportive care) administered in a mitigative regimen, 1–48 hours after irradiation. Following exposure to LD50-70/40 of radiation, injection of efficacious doses of entolimod administered as late as 25 hours thereafter reduced the risk of mortality 2-3-fold, providing a statistically significant (P<0.01) absolute survival advantage of 40–60% compared to vehicle treatment. Similar magnitude of survival improvement was also achieved with drug delivered 48 hours after irradiation. Improved survival was accompanied by predominantly significant (P<0.05) effects of entolimod administration on accelerated morphological recovery of hematopoietic and immune system organs, decreased severity and duration of thrombocytopenia, anemia and neutropenia, and increased clonogenic potential of the bone marrow compared to control irradiated animals. Entolimod treatment also led to reduced apoptosis and accelerated crypt regeneration in the gastrointestinal tract. Together, these data indicate that entolimod is a highly promising potential life-saving treatment for victims of radiation disasters. PMID:26367124

  3. A review of primary writing tremor.

    PubMed

    Rana, Abdul Qayyum; Vaid, Haris M

    2012-03-01

    A task-specific tremor (TST) is a rare form of movement disorder that appears while performing or attempting to perform a particular task. Primary writing tremor (PWT) is the most common form of TST which only occurs during the act of writing and hinders it. (Bain PG, Findley LJ, Britton TC, Rothwell JC, Gresty MA, Thompson PD, Marsden CD. MRC Human Movement, and Balance Unit, Institute of Neurology, London, UK. Primary writing tremor. Brain. 1995;118(6):1461-72.) Primary writing tremor type B is present not only during the act of writing but also when the hand assumes a writing posture. (Bain PG, Findley LJ, Britton TC, Rothwell JC, Gresty MA, Thompson PD, Marsden CD. MRC Human Movement and Balance Unit, Institute of Neurology, London, UK. Primary writing tremor. Brain. 1995;118(6):1461-72.) We first of all describe a remarkable case study of a 50-year old, right-handed male who started experiencing a primary writing tremor in his right hand about a year ago. This case was found to be of particular interest because the patient had it relatively difficult when attempting to write numbers as opposed to writing letters. This review further discusses the clinical manifestations of PWT. In addition, three main hypotheses have been proposed for the causation of PWT, although the exact pathophysiology of PWT still remains unknown. It has been suggested that PWT is a separate entity, a variant of essential tremor and not a separate entity, or a type of dystonia. The various treatment options for PWT are discussed including botulinum toxin and oral pharmacotherapy.

  4. Monitoring of Tumor Promotion and Progression in a Mouse Model of Inflammation-Induced Colon Cancer with Magnetic Resonance Colonography1

    PubMed Central

    Young, Matthew R; Ileva, Lilia V; Bernardo, Marcelino; Riffle, Lisa A; Jones, Yava L; Kim, Young S; Colburn, Nancy H; Choyke, Peter L

    2009-01-01

    Early detection of precancerous tissue has significantly improved survival of most cancers including colorectal cancer (CRC). Animal models designed to study the early stages of cancer are valuable for identifying molecular events and response indicators that correlate with the onset of disease. The goal of this work was to investigate magnetic resonance (MR) colonography in a mouse model of CRC on a clinical MR imager. Mice treated with azoxymethane and dextran sulfate sodium were imaged by serial MR colonography (MRC) from initiation to euthanasia. Magnetic resonance colonography was obtained with both T1- and T2-weighted images after administration of a Fluorinert enema to remove residual luminal signal and intravenous contrast to enhance the colon wall. Individual tumor volumes were calculated and validated ex vivo. The Fluorinert enema provided a clear differentiation of the lumen of the colon from the mucosal lining. Inflammation was detected 3 days after dextran sulfate sodium exposure and subsided during the next week. Tumors as small as 1.2 mm3 were detected and as early as 29 days after initiation. Individual tumor growths were followed over time, and tumor volumes were measured by MR imaging correlated with volumes measured ex vivo. The use of a Fluorinert enema during MRC in mice is critical for differentiating mural processes from intraluminal debris. Magnetic resonance colonography with Fluorinert enema and intravenous contrast enhancement will be useful in the study of the initial stages of colon cancer and will reduce the number of animals needed for preclinical trials of prevention or intervention. PMID:19242605

  5. Deciphering an underlying mechanism of differential cellular effects of nanoparticles: an example of Bach-1 dependent induction of HO-1 expression by gold nanorod.

    PubMed

    Fan, Zhenlin; Yang, Xiao; Li, Yiye; Li, Suping; Niu, Shiwen; Wu, Xiaochun; Wei, Jingyan; Nie, Guangjun

    2012-12-01

    Gold nanoparticles are extensively investigated for their potential biomedical applications. Therefore, it is pertinent to thoroughly evaluate their biological effects at different levels and their underlying molecular mechanism. Frequently, there are discrepancies about the biological effects of various gold nanoparticles among the reports dealing with different models. Most of the studies focused on the different biological effects of various nano-properties of the nanomaterials. We hypothesize that the biological models with different metabolic processes would be taken into account to explain the observed discrepancies of biological effects of nanomaterials. Herein, by using mouse embryo fibroblast cell line (MEF-1) and human embryonal lung fibroblast cell line (MRC-5) as in vitro models, we studied the cellular effects of gold nanorods (AuNRs) coated with poly (diallyldimethyl ammonium chloride) (PDDAC), polyethylene glycol and polystyrene sulfonae (PSS). We found that all three AuNRs had no effects on cellular viability at the concentration of 1 nM; however, AuNRs that coated with PDDAC and PSS induced significant up-regulation of heme oxygenase-1 (HO-1) which was believed to be involved in cellular defense activities in MEF-1 but not in MRC-5 cells. Further study showed that the low fundamental expression of transcription factor Bach-1, the major regulator of HO-1 expression, in MEF-1 was responsible for the up-regulation of HO-1 induced by the AuNRs. Our results indicate that although AuNRs we used are non-cytotoxic, they cell-specifically induce change of gene expression, such as HO-1. Our current study provides a good example to explain the molecular mechanisms of differential biological effects of nanomaterials in different cellular models. This finding raises a concern on evaluation of cellular effects of nanoparticles where the cell models should be critically considered.

  6. MT-HESS: an efficient Bayesian approach for simultaneous association detection in OMICS datasets, with application to eQTL mapping in multiple tissues

    PubMed Central

    Lewin, Alex; Saadi, Habib; Peters, James E.; Moreno-Moral, Aida; Lee, James C.; Smith, Kenneth G. C.; Petretto, Enrico; Bottolo, Leonardo; Richardson, Sylvia

    2016-01-01

    Motivation: Analysing the joint association between a large set of responses and predictors is a fundamental statistical task in integrative genomics, exemplified by numerous expression Quantitative Trait Loci (eQTL) studies. Of particular interest are the so-called ‘hotspots’, important genetic variants that regulate the expression of many genes. Recently, attention has focussed on whether eQTLs are common to several tissues, cell-types or, more generally, conditions or whether they are specific to a particular condition. Results: We have implemented MT-HESS, a Bayesian hierarchical model that analyses the association between a large set of predictors, e.g. SNPs, and many responses, e.g. gene expression, in multiple tissues, cells or conditions. Our Bayesian sparse regression algorithm goes beyond ‘one-at-a-time’ association tests between SNPs and responses and uses a fully multivariate model search across all linear combinations of SNPs, coupled with a model of the correlation between condition/tissue-specific responses. In addition, we use a hierarchical structure to leverage shared information across different genes, thus improving the detection of hotspots. We show the increase of power resulting from our new approach in an extensive simulation study. Our analysis of two case studies highlights new hotspots that would remain undetected by standard approaches and shows how greater prediction power can be achieved when several tissues are jointly considered. Availability and implementation: C++ source code and documentation including compilation instructions are available under GNU licence at http://www.mrc-bsu.cam.ac.uk/software/. Contact: sylvia.richardson@mrc-bsu.cam.ac.uk or lb664@cam.ac.uk Supplementary information: Supplementary data are available at Bioinformatics online. PMID:26504141

  7. Assessment of biological and biochemical indicators in soil under transgenic Bt and non-Bt cotton crop in a sub-tropical environment.

    PubMed

    Sarkar, Binoy; Patra, Ashok K; Purakayastha, T J; Megharaj, Mallavarapu

    2009-09-01

    There is concern that transgenic Bt-crops carry genes that could have undesirable effects on natural and agro-ecosystem functions. We investigated the effect of Bt-cotton (expressing the Cry 1Ac protein) on several microbial and biochemical indicators in a sandy loam soil. Bt-cotton (MRC-6301Bt) and its non-transgenic near-isoline (MRC-6301) were grown in a net-house on a sandy clay loam soil. Soil and root samples were collected 60, 90, and 120 days after sowing. Soil from a control (no-crop) treatment was also included. Samples were analysed for microbial biomass C, N and P (MBC, MBN, MBP), total organic carbon (TOC), and several soil enzyme activities. The microbial quotient (MQ) was calculated as the ratio of MBC-to-TOC. The average of the three sampling events revealed a significant increase in MBC, MBN, MBP and MQ in the soil under Bt-cotton over the non-Bt isoline. The TOC was similar in Bt and non-Bt systems. Potential N mineralization, nitrification, nitrate reductase, and acid and alkaline phosphatase activities were all higher in the soil under Bt-cotton. Root dry weights were not different (P > 0.05), but root volume of Bt-cotton was higher on 90 and 120 days than that of non-Bt cotton. The time of sampling strongly affected the above parameters, with most being highest on 90 days after sowing. We concluded from the data that there were some positive or no negative effects of Bt-cotton on the studied indicators, and therefore cultivation of Bt-cotton appears to be no risk to soil ecosystem functions.

  8. Genome-Wide Architecture of Disease Resistance Genes in Lettuce.

    PubMed

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

    2015-10-08

    Genome-wide motif searches identified 1134 genes in the lettuce reference genome of cv. Salinas that are potentially involved in pathogen recognition, of which 385 were predicted to encode nucleotide binding-leucine rich repeat receptor (NLR) proteins. Using a maximum-likelihood approach, we grouped the NLRs into 25 multigene families and 17 singletons. Forty-one percent of these NLR-encoding genes belong to three families, the largest being RGC16 with 62 genes in cv. Salinas. The majority of NLR-encoding genes are located in five major resistance clusters (MRCs) on chromosomes 1, 2, 3, 4, and 8 and cosegregate with multiple disease resistance phenotypes. Most MRCs contain primarily members of a single NLR gene family but a few are more complex. MRC2 spans 73 Mb and contains 61 NLRs of six different gene families that cosegregate with nine disease resistance phenotypes. MRC3, which is 25 Mb, contains 22 RGC21 genes and colocates with Dm13. A library of 33 transgenic RNA interference tester stocks was generated for functional analysis of NLR-encoding genes that cosegregated with disease resistance phenotypes in each of the MRCs. Members of four NLR-encoding families, RGC1, RGC2, RGC21, and RGC12 were shown to be required for 16 disease resistance phenotypes in lettuce. The general composition of MRCs is conserved across different genotypes; however, the specific repertoire of NLR-encoding genes varied particularly of the rapidly evolving Type I genes. These tester stocks are valuable resources for future analyses of additional resistance phenotypes.

  9. Fisetin inhibits cellular proliferation and induces mitochondria-dependent apoptosis in human gastric cancer cells.

    PubMed

    Sabarwal, Akash; Agarwal, Rajesh; Singh, Rana P

    2017-02-01

    The anticancer effects of fisetin, a dietary agent, are largely unknown against human gastric cancer. Herein, we investigated the mechanisms of fisetin-induced inhibition of growth and survival of human gastric carcinoma AGS and SNU-1 cells. Fisetin (25-100 μM) caused significant decrease in the levels of G1 phase cyclins and CDKs, and increased the levels of p53 and its S15 phosphorylation in gastric cancer cells. We also observed that growth suppression and death of non-neoplastic human intestinal FHs74int cells were minimally affected by fisetin. Fisetin strongly increased apoptotic cells and showed mitochondrial membrane depolarization in gastric cancer cells. DNA damage was observed as early as 3 h after fisetin treatment which was accompanied with gamma-H2A.X(S139) phosphorylation and cleavage of PARP. Fisetin-induced apoptosis was observed to be independent of p53. DCFDA and MitoSOX analyses showed an increase in mitochondrial ROS generation in time- and dose-dependent fashion. It also increased cellular nitrite and superoxide generation. Pre-treatment with N-acetyl cysteine (NAC) inhibited ROS generation and also caused protection from fisetin-induced DNA damage. The formation of comets were observed in only fisetin treated cells which was blocked by NAC pre-treatment. Further investigation of the source of ROS, using mitochondrial respiratory chain (MRC) complex inhibitors, suggested that fisetin caused ROS generation specifically through complex I. Collectively, these results for the first time demonstrated that fisetin possesses anticancer potential through ROS production most likely via MRC complex I leading to apoptosis in human gastric carcinoma cells. © 2016 Wiley Periodicals, Inc.

  10. Comparative study on oviposition and larval preference of spotted bollworm, Earias vittella on Bt and non-Bt cotton.

    PubMed

    Shera, P S; Arora, Ramesh

    2016-01-01

    Oviposition and larval preference of spotted bollworm, Earias vittella (Fabricius) was assessed on four transgenic Bt cotton hybrids, viz. MRC 6304 Bt (cry1Ac gene), JKCH 1947 Bt (modified cry1Ac gene), NCEH 6R Bt (cry1Ab/cry1Ac fused gene) and MRC 7017 BG II (cry1Ac and cry2Ab genes) in comparison to the respective isogenic cotton. The results showed that Bt toxin did not deter oviposition preference of E. vittella moths as there was no significant difference in the number of eggs laid on squares/bolls of Bt and non-Bt cotton hybrids, across different crop growth stages. There was also no behavioral change in larval preference with respect to selecting non-Bt cotton in comparison to Bt cotton. Floral bodies from Bt and the respective isogenic cotton genotypes were equally preferred by both first and third instar larvae after 24 hrs indicating that initial selection was independent of susceptibility to Bt toxin. However, E. vittella larvae showed significant difference in preference for different cotton genotypes. Studies on the relative preference indicated that third instar larvae had greater preference for bolls (7.29-7.50%) than for the squares (5.0-5.21%) and reverse was true for the first instar larvae which showed greater preference for squares (7.08-7.29%) than for the bolls (5.21-5.42%), in a multiple-choice test. It may be concluded that oviposition and larval preference of E. vittella did not differ significantly between Bt and isogenic non-Bt cotton genotypes.

  11. Bronchoscopic thermal vapour ablation therapy in the management of heterogeneous emphysema.

    PubMed

    Snell, Gregory; Herth, Felix J F; Hopkins, Peter; Baker, Kimberley M; Witt, Christian; Gotfried, Mark H; Valipour, Arschang; Wagner, Manfred; Stanzel, Franz; Egan, Jim J; Kesten, Steven; Ernst, Armin

    2012-06-01

    The need for a less invasive procedure than surgical lung volume reduction that can produce consistent improvements with reduced morbidity remains a medical goal in patients with emphysema. We sought to determine the effect of bronchoscopic thermal vapour ablation (BTVA) on lung volumes and outcomes in patients with emphysema. 44 patients with upper lobe-predominant emphysema were treated unilaterally with BTVA. Entry criteria included: age 40-75 yrs, forced expiratory volume in 1 s (FEV(1)) 15-45% predicted, previous pulmonary rehabilitation and a heterogeneity index (tissue/air ratio of lower lobe/upper lobe) from high-resolution computed tomography (HRCT) ≥ 1.2. Changes in FEV(1), St George's Respiratory Questionnaire (SGRQ), 6-min walk distance (6 MWD), modified Medical Research Council (mMRC) dyspnoea score, and hyperinflation were measured at baseline, and 3 and 6 months post-BTVA. At 6 months, mean ± SE FEV(1) improved by 141 ± 26 mL (p<0.001) and residual volume was reduced by 406 ± 113 mL (p<0.0001). SGRQ total score improved by 14.0 ± 2.4 points (p<0.001), with 73% improving by ≥ 4 points. Improvements were observed in 6 MWD (46.5 ± 10.6 m) and mMRC dyspnoea score (0.9 ± 0.2) (p<0.001 for both). Lower respiratory events (n=11) were the most common adverse event and occurred most often during the initial 30 days. BTVA therapy results in clinically relevant improvements in lung function, quality of life and exercise tolerance in upper lobe predominant emphysema.

  12. Advancements in automatic marking with range pattern matching

    NASA Astrophysics Data System (ADS)

    Salazar, D.; Valadez, J.

    2013-06-01

    In previous work, an approach was detailed using CATS-MRCC-RPM, where new pattern matching functionality is used to find locations on a jobdeck that are suitable for mark placements and ultimately, metrology tool measurement locations. These locations are found by first creating pattern definitions. The defined patterns are passed to the CATS MRCC-RPM match algorithm which in turn outputs all found locations that match the description. In that previous work, the pattern definitions, also known as mark templates, had several limitations. For example, each template could hold only one mark placed at its center, and had to be symmetrical. This was considered to be severely limiting in nature and not production worthy for advanced mask manufacturing. This paper builds on top of the previous one in various ways, extends the possibilities, and provides mask makers unlimited options for extending metrology automation. Mark templates are expanded upon to hold multiple marks at different offsets from its center, and even of different types. Each template can be symmetrical or asymmetrical, and yet all the marks on it can still be correctly placed by taking advantage of match orientation information during the Classification step. Placement of other mark types beyond basic ones is also explored, such as Arbitrary Area. Lastly, the classification step is an enhancement process that thoroughly manages the use of chip/mark information. The result makes use of the output of JD MRC (jobdeck MRC) which executes RPM on jobdecks by chip in order to reduce redundant chips processing, rather than search all chip placements by extension.

  13. Epigenetic modulation upon exposure of lung fibroblasts to TiO2 and ZnO nanoparticles: alterations in DNA methylation

    PubMed Central

    Patil, Nayana A; Gade, WN; Deobagkar, Deepti D

    2016-01-01

    Titanium dioxide (TiO2) and zinc oxide (ZnO) nanoparticles (NPs) are promising candidates for numerous applications in consumer products. This will lead to increased human exposure, thus posing a threat to human health. Both these types of NPs have been studied for their cell toxicity, immunotoxicity, and genotoxicity. However, effects of these NPs on epigenetic modulations have not been studied. Epigenetics is an important link in the genotype and phenotype modulation and misregulation can often lead to lifestyle diseases. In this study, we have evaluated the DNA methylation-based epigenetic changes upon exposure to various concentrations of NPs. The investigation was designed to evaluate global DNA methylation, estimating the corresponding methyltransferase activity and expression of Dnmt gene using lung fibroblast (MRC5) cell line as lungs are the primary route of entry and target of occupational exposure to TiO2 and ZnO NPs. Enzyme-linked immunosorbent assay-based immunochemical assay revealed dose-related decrease in global DNA methylation and DNA methyltransferase activity. We also found direct correlation between the concentration of NPs, global methylation levels, and expression levels of Dnmt1, 3A, and 3B genes upon exposure. This is the first study to investigate effect of exposure to TiO2 and ZnO on DNA methylation levels in MRC5 cells. Epigenetic processes are known to play an important role in reprogramming and adaptation ability of an organism and can have long-term consequences. We suggest that changes in DNA methylation can serve as good biomarkers for early exposure to NPs since they occur at concentrations well below the sublethal levels. Our results demonstrate a clear epigenetic alteration in response to metal oxide NPs and that this effect was dose-dependent. PMID:27660443

  14. Gastric cancer: Current status of lymph node dissection

    PubMed Central

    Degiuli, Maurizio; De Manzoni, Giovanni; Di Leo, Alberto; D’Ugo, Domenico; Galasso, Erica; Marrelli, Daniele; Petrioli, Roberto; Polom, Karol; Roviello, Franco; Santullo, Francesco; Morino, Mario

    2016-01-01

    D2 procedure has been accepted in Far East as the standard treatment for both early (EGC) and advanced gastric cancer (AGC) for many decades. Recently EGC has been successfully treated with endoscopy by endoscopic mucosal resection or endoscopic submucosal dissection, when restricted or extended Gotoda's criteria can be applied and D1+ surgery is offered only to patients not fitted for less invasive treatment. Furthermore, two randomised controlled trials (RCTs) have been demonstrating the non inferiority of minimally invasive technique as compared to standard open surgery for the treatment of early cases and recently the feasibility of adequate D1+ dissection has been demonstrated also for the robot assisted technique. In case of AGC the debate on the extent of nodal dissection has been open for many decades. While D2 gastrectomy was performed as the standard procedure in eastern countries, mostly based on observational and retrospective studies, in the west the Medical Research Council (MRC), Dutch and Italian RCTs have been conducted to show a survival benefit of D2 over D1 with evidence based medicine. Unfortunately both the MRC and the Dutch trials failed to show a survival benefit after the D2 procedure, mostly due to the significant increase of postoperative morbidity and mortality, which was referred to splenopancreatectomy. Only 15 years after the conclusion of its accrual, the Dutch trial could report a significant decrease of recurrence after D2 procedure. Recently the long term survival analysis of the Italian RCT could demonstrate a benefit for patients with positive nodes treated with D2 gastrectomy without splenopancreatectomy. As nowadays also in western countries D2 procedure can be done safely with pancreas preserving technique and without preventive splenectomy, it has been suggested in several national guidelines as the recommended procedure for patients with AGC. PMID:26973384

  15. Silicon-based quantum dots induce inflammation in human lung cells and disrupt extracellular matrix homeostasis.

    PubMed

    Stan, Miruna-Silvia; Sima, Cornelia; Cinteza, Ludmila Otilia; Dinischiotu, Anca

    2015-08-01

    Quantum dots (QDs) are nanocrystalline semiconductor materials that have been tested for biological applications such as cancer therapy, cellular imaging and drug delivery, despite the serious lack of information of their effects on mammalian cells. The present study aimed to evaluate the potential of Si/SiO2 QDs to induce an inflammatory response in MRC-5 human lung fibroblasts. Cells were exposed to different concentrations of Si/SiO2 QDs (25-200 μg·mL(-1)) for 24, 48, 72 and 96 h. The results obtained showed that uptake of QDs was dependent on biocorona formation and the stability of nanoparticles in various biological media (minimum essential medium without or with 10% fetal bovine serum). The cell membrane damage indicated by the increase in lactate dehydrogenase release after exposure to QDs was dose- and time-dependent. The level of lysosomes increased proportionally with the concentration of QDs, whereas an accumulation of autophagosomes was also observed. Cellular morphology was affected, as shown by the disruption of actin filaments. The enhanced release of nitric oxide and the increase in interleukin-6 and interleukin-8 protein expression suggested that nanoparticles triggered an inflammatory response in MRC-5 cells. QDs decreased the protein expression and enzymatic activity of matrix metalloproteinase (MMP)-2 and MMP-9 and also MMP-1 caseinase activity, whereas the protein levels of MMP-1 and tissue inhibitor of metalloproteinase-1 increased. The present study reveals for the first time that silicon-based QDs are able to generate inflammation in lung cells and cause an imbalance in extracellular matrix turnover through a differential regulation of MMPs and tissue inhibitor of metalloproteinase-1 protein expression.

  16. Structural and functional alterations in mitochondrial membrane in picrotoxin-induced epileptic rat brain.

    PubMed

    Acharya, Munjal M; Katyare, Surendra S

    2005-03-01

    Mitochondrial function is a key determinant of both excitability and viability of neurons. Present studies were carried out to decipher cerebral mitochondrial oxidative energy metabolism and membrane function in the chronic condition of generalized seizures induced by picrotoxin (PTX) in rats. PTX-induced convulsions resulted in decreased respiration rates (14-41%) with glutamate, pyruvate + malate, and succinate as substrate. The ADP phosphorylation rates were drastically reduced by 44-65%. An opposite trend was observed with ascorbate + N,N,N',N'-tetramethyl-p-phenylenediamine [corrected] (TMPD) as substrate. In general, uncoupling of the mitochondrial electron transport was observed after PTX treatment. Malate dehydrogenase (MDH) and succinate dehydrogenase (SDH) activities were decreased by 20-80%; also, there was significant reduction in cytochrome b content after PTX treatment, while the F(o)F(1) ATPase (complex V) activity increased in basal and 2,4-dinitrophenol (DNP)-stimulated condition, indicating increased membrane fragility. The substrate kinetics analysis had shown that K(m) and V(max) of the higher affinity kinetic component of ATPase increased significantly by 1.2- to 1.4-fold in epileptic condition. Temperature kinetic analysis revealed 1.2-fold increase in energies of activation with decreased transition temperature. The total phospholipid (TPL) and cholesterol (CHL) contents decreased significantly with lowering of diphosphatidylglycerol (DPG), phosphatidylethanolamine (PE), phosphatidylinositol (PI), and phosphatidylserine (PS), while lysophospholipid (lyso), sphingomyelin (SPM), and phosphatidylcholine components were found to be elevated. Brain mitochondrial membrane was somewhat more fluidized in epileptic animals. Possible consequences of mitochondrial respiratory chain (MRC) dysfunction are discussed. In conclusion, impairment of MRC function along with structural alterations suggests novel pathophysiological mechanisms important for

  17. The Toll-Like Receptor 5 Agonist Entolimod Mitigates Lethal Acute Radiation Syndrome in Non-Human Primates.

    PubMed

    Krivokrysenko, Vadim I; Toshkov, Ilia A; Gleiberman, Anatoli S; Krasnov, Peter; Shyshynova, Inna; Bespalov, Ivan; Maitra, Ratan K; Narizhneva, Natalya V; Singh, Vijay K; Whitnall, Mark H; Purmal, Andrei A; Shakhov, Alexander N; Gudkov, Andrei V; Feinstein, Elena

    2015-01-01

    There are currently no approved medical radiation countermeasures (MRC) to reduce the lethality of high-dose total body ionizing irradiation expected in nuclear emergencies. An ideal MRC would be effective even when administered well after radiation exposure and would counteract the effects of irradiation on the hematopoietic system and gastrointestinal tract that contribute to its lethality. Entolimod is a Toll-like receptor 5 agonist with demonstrated radioprotective/mitigative activity in rodents and radioprotective activity in non-human primates. Here, we report data from several exploratory studies conducted in lethally irradiated non-human primates (rhesus macaques) treated with a single intramuscular injection of entolimod (in the absence of intensive individualized supportive care) administered in a mitigative regimen, 1-48 hours after irradiation. Following exposure to LD50-70/40 of radiation, injection of efficacious doses of entolimod administered as late as 25 hours thereafter reduced the risk of mortality 2-3-fold, providing a statistically significant (P<0.01) absolute survival advantage of 40-60% compared to vehicle treatment. Similar magnitude of survival improvement was also achieved with drug delivered 48 hours after irradiation. Improved survival was accompanied by predominantly significant (P<0.05) effects of entolimod administration on accelerated morphological recovery of hematopoietic and immune system organs, decreased severity and duration of thrombocytopenia, anemia and neutropenia, and increased clonogenic potential of the bone marrow compared to control irradiated animals. Entolimod treatment also led to reduced apoptosis and accelerated crypt regeneration in the gastrointestinal tract. Together, these data indicate that entolimod is a highly promising potential life-saving treatment for victims of radiation disasters.

  18. Synthesis, Characterization, and Cytotoxicity of Platinum(IV) Carbamate Complexes

    PubMed Central

    Wilson, Justin J.; Lippard, Stephen J.

    2011-01-01

    The synthesis, characterization, and cytotoxicity of eight new platinum(IV) complexes having the general formula, c,c,t-[Pt(NH3)2Cl2(O2CNHR)2], are reported, where R = tert-butyl (4), cyclopentyl (5), cyclohexyl (6), phenyl (7), p-tolyl (8), p-anisole (9), 4-fluorophenyl (10), or 1-naphthyl (11). These compounds were synthesized by reacting organic isocyanates with the platinum(IV) complex, c,c,t-[Pt(NH3)2Cl2(OH)2]. The electrochemistry of the compounds was investigated by cyclic voltammetry. The aryl carbamate complexes 7 – 11 exhibit reduction peak potentials near −720 mV vs. Ag/AgCl, whereas the alkyl carbamate complexes display reduction peak potentials between −820 and −850 mV vs. Ag/AgCl. The cyclic voltammograms of c,c,t-[Pt(NH3)2Cl2(O2CCH3)2] (1), c,c,t-[Pt(NH3)2Cl2(O2CCF3)2] (2), and cis-[Pt(NH3)2Cl4] (3) were measured for comparison. Density functional theory (DFT) studies were undertaken to investigate the electronic structures of 1 – 11 and to determine their adiabatic electron affinities. A linear correlation (R2 = 0.887) between computed adiabatic electron affinities and measured reduction peak potential was discovered. The biological activity of 4 – 11 and, for comparison, cisplatin was evaluated in human lung cancer A549 and normal MRC-5 cells by the MTT assay. The compounds exhibit comparable or slightly better activity than cisplatin against the A549 cells. In MRC-5 cells, all are equally or slightly less cytotoxic than cisplatin, except for 4 and 5, which are more toxic. PMID:21361279

  19. Muscle MRI in Duchenne muscular dystrophy: Evidence of a distinctive pattern.

    PubMed

    Polavarapu, Kiran; Manjunath, Mahadevappa; Preethish-Kumar, Veeramani; Sekar, Deepha; Vengalil, Seena; Thomas, PriyaTreesa; Sathyaprabha, Talakad N; Bharath, Rose Dawn; Nalini, Atchayaram

    2016-11-01

    The purpose of this study was to describe the pattern of muscle involvement using MRI findings and correlate with functional as well as muscle strength measurements. Fifty genetically confirmed DMD children with a mean age of 7.6 ± 2.8 (4-15 years) underwent muscle MRI and qualitative assessment was done for muscle changes using Mercuri staging for fibro-fatty replacement on T1 sequence and Borsato score for myoedema on STIR sequence. Detailed phenotypic characterisation was done with Manual muscle testing (modified MRC grading) and Muscular Dystrophy Functional Rating Scale (MDFRS). Mercuri scoring showed severe fibro-fatty changes in Gluteus medius, minimus and Adductor magnus followed by moderate to severe changes in Gluteus maximus and Quadriceps muscles. Total sparing of Gracilis, Sartorius and Semimembranosus muscles was observed. Superficial posterior and lateral leg muscles were preferentially involved with sparing of deep posterior and anterior leg muscles. Myoedema showed significant inverse correlation with fatty infiltration in thigh muscles. Similarly, significant inverse correlation was observed between Mercuri scores and MRC grading as well as MDFRS scores. A direct linear correlation was observed between duration of illness and fibro-fatty changes in piriformis, quadriceps and superficial posterior leg muscles. There was no correlation between MRI findings and genotypic characteristics. However, this specific pattern of muscle involvement in MRI could aid in proceeding for genetic testing when clinical suspicion is high, thus reducing the need for muscle biopsy. Fibro fatty infiltration as measured by Mercuri scoring can be a useful marker for assessing the disease severity and progression.

  20. New GOLD classification: longitudinal data on group assignment

    PubMed Central

    2014-01-01

    Rationale Little is known about the longitudinal changes associated with using the 2013 update of the multidimensional GOLD strategy for chronic obstructive pulmonary disease (COPD). Objective To determine the COPD patient distribution of the new GOLD proposal and evaluate how this classification changes over one year compared with the previous GOLD staging based on spirometry only. Methods We analyzed data from the CHAIN study, a multicenter observational Spanish cohort of COPD patients who are monitored annually. Categories were defined according to the proposed GOLD: FEV1%, mMRC dyspnea, COPD Assessment Test (CAT), Clinical COPD Questionnaire (CCQ), and exacerbations-hospitalizations. One-year follow-up information was available for all variables except CCQ data. Results At baseline, 828 stable COPD patients were evaluated. On the basis of mMRC dyspnea versus CAT, the patients were distributed as follows: 38.2% vs. 27.2% in group A, 17.6% vs. 28.3% in group B, 15.8% vs. 12.9% in group C, and 28.4% vs. 31.6% in group D. Information was available for 526 patients at one year: 64.2% of patients remained in the same group but groups C and D show different degrees of variability. The annual progression by group was mainly associated with one-year changes in CAT scores (RR, 1.138; 95%CI: 1.074-1.206) and BODE index values (RR, 2.012; 95%CI: 1.487-2.722). Conclusions In the new GOLD grading classification, the type of tool used to determine the level of symptoms can substantially alter the group assignment. A change in category after one year was associated with longitudinal changes in the CAT and BODE index. PMID:24417879

  1. Modulation of Rho GTPases rescues brain mitochondrial dysfunction, cognitive deficits and aberrant synaptic plasticity in female mice modeling Rett syndrome.

    PubMed

    De Filippis, Bianca; Valenti, Daniela; Chiodi, Valentina; Ferrante, Antonella; de Bari, Lidia; Fiorentini, Carla; Domenici, Maria Rosaria; Ricceri, Laura; Vacca, Rosa Anna; Fabbri, Alessia; Laviola, Giovanni

    2015-06-01

    Rho GTPases are molecules critically involved in neuronal plasticity and cognition. We have previously reported that modulation of brain Rho GTPases by the bacterial toxin CNF1 rescues the neurobehavioral phenotype in MeCP2-308 male mice, a model of Rett syndrome (RTT). RTT is a rare X-linked neurodevelopmental disorder and a genetic cause of intellectual disability, for which no effective therapy is available. Mitochondrial dysfunction has been proposed to be involved in the mechanism of the disease pathogenesis. Here we demonstrate that modulation of Rho GTPases by CNF1 rescues the reduced mitochondrial ATP production via oxidative phosphorylation in the brain of MeCP2-308 heterozygous female mice, the condition which more closely recapitulates that of RTT patients. In RTT mouse brain, CNF1 also restores the alterations in the activity of the mitochondrial respiratory chain (MRC) complexes and of ATP synthase, the molecular machinery responsible for the majority of cell energy production. Such effects were achieved through the upregulation of the protein content of those MRC complexes subunits, which were defective in RTT mouse brain. Restored mitochondrial functionality was accompanied by the rescue of deficits in cognitive function (spatial reference memory in the Barnes maze), synaptic plasticity (long-term potentiation) and Tyr1472 phosphorylation of GluN2B, which was abnormally enhanced in the hippocampus of RTT mice. Present findings bring into light previously unknown functional mitochondrial alterations in the brain of female mice modeling RTT and provide the first evidence that RTT brain mitochondrial dysfunction can be rescued by modulation of Rho GTPases.

  2. Synthesis and antibacterial evaluation of a new series of N-Alkyl-2-alkynyl/(E)-alkenyl-4-(1H)-quinolones.

    PubMed

    Wube, Abraham; Guzman, Juan-David; Hüfner, Antje; Hochfellner, Christina; Blunder, Martina; Bauer, Rudolf; Gibbons, Simon; Bhakta, Sanjib; Bucar, Franz

    2012-07-09

    To gain further insight into the structural requirements of the aliphatic group at position 2 for their antimycobacterial activity, some N-alkyl-4-(1H)-quinolones bearing position 2 alkynyls with various chain length and triple bond positions were prepared and tested for in vitro antibacterial activity against rapidly-growing strains of mycobacteria, the vaccine strain Mycobacterium bovis BCG, and methicillin-resistant Staphylococcus aureus strains, EMRSA-15 and -16. The compounds were also evaluated for inhibition of ATP-dependent MurE ligase of Mycobacterium tuberculosis. The lowest MIC value of 0.5 mg/L (1.2-1.5 µM) was found against M. fortuitum and M. smegmatis. These compounds displayed no or only weak toxicity to the human lung fibroblast cell line MRC-5 at 100 µM concentration. The quinolone derivatives exhibited pronounced activity against the epidemic MRSA strains (EMRSA-15 and -16) with MIC values of 2-128 mg/L (5.3-364.7 µM), and M. bovis BCG with an MIC value of 25 mg/L (66.0-77.4 µM). In addition, the compounds inhibited the MurE ligase of M. tuberculosis with moderate to weak activity showing IC50 values of 200-774 µM. The increased selectivity towards mycobacterial bacilli with reference to MRC-5 cells observed for 2-alkynyl quinolones compared to their corresponding 2-alkenyl analogues serves to highlight the mycobacterial specific effect of the triple bond. Exploration of a terminal bromine atom at the side chain of N-alkyl-2-(E)-alkenyl-4-(1H)-quinolones showed improved antimycobacterial activity whereas a cyclopropyl residue at N-1 was suggested to be detrimental to antibacterial activity.

  3. Progress on a small multi-cycling cryogenic fluid flow valve

    NASA Astrophysics Data System (ADS)

    Weilert, M.; Hahn, I.; Barmatz, M.; Higham, D.; Frodsham, G.

    2001-11-01

    Mission Research Corporation (MRC) in cooperation with the Jet Propulsion Laboratory (JPL) has developed a new small remote-controlled fluid valve. The motivation for developing this valve came from the requirements of a future International Space Station experiment called Microgravity Scaling Theory Experiment (MISTE). This experiment requires an in situ, low-temperature operated, fluid valve that can be open/closed over 50 times during a 4.5 month flight. The successful operation of MISTE and other space-based and ground-based laboratory experiments now in development will require reliable cryogenic fluid valves that are remotely operated, helium leak tight, non-magnetic, very low power, and which have a small dead volume. The new valve is normally closed and requires fluid actuation at a pressure of approximately 600 kPa to open. The heart of the valve design is found in the configuration of the valve seat and sealing poppet. The design of these two surfaces was derived from work performed previously during a five year development program for a larger MRC remote-controlled, cryogenic fluid flow control valve. More than 50 of the larger valves have been produced and delivered for space flight applications. The new small valve has only three moving parts, which move less than 0.012 cm when the valve fully opens or closes. The bearing surfaces in the valve operating mechanism are all flexure (except for the valve poppet) and thus the valve is expected to have a lifetime of thousands of open/close cycles. The materials and processes used to fabricate the new valve have been flight certified. Results from the first extensively tested prototype show repeatable behavior with a leak rate of typically 3×10 -8 scc/ s after the first open/close cycle at 4.2 K, rising to about 10 -6 scc/ s after 100 cycles. Further tests and minor modifications are expected to improve the performance.

  4. 'Saving the lives of our dogs': the development of canine distemper vaccine in interwar Britain.

    PubMed

    Bresalier, Michael; Worboys, Michael

    2014-06-01

    This paper examines the successful campaign in Britain to develop canine distemper vaccine between 1922 and 1933. The campaign mobilized disparate groups around the common cause of using modern science to save the nation's dogs from a deadly disease. Spearheaded by landed patricians associated with the country journal The Field, and funded by dog owners and associations, it relied on collaborations with veterinary professionals, government scientists, the Medical Research Council (MRC) and the commercial pharmaceutical house the Burroughs Wellcome Company (BWC). The social organization of the campaign reveals a number of important, yet previously unexplored, features of interwar science and medicine in Britain. It depended on a patronage system that drew upon a large base of influential benefactors and public subscriptions. Coordinated by the Field Distemper Fund, this system was characterized by close relationships between landed elites and their social networks with senior science administrators and researchers. Relations between experts and non-experts were crucial, with high levels of public engagement in all aspects of research and vaccine development. At the same time, experimental and commercial research supported under the campaign saw dynamic interactions between animal and human medicine, which shaped the organization of the MRC's research programme and demonstrated the value of close collaboration between veterinary and medical science, with the dog as a shared object and resource. Finally, the campaign made possible the translation of 'laboratory' findings into field conditions and commercial products. Rather than a unidirectional process, translation involved negotiations over the very boundaries of the 'laboratory' and the 'field', and what constituted a viable vaccine. This paper suggests that historians reconsider standard historical accounts of the nature of patronage, the role of animals, and the interests of landed elites in interwar British

  5. Administration of CoQ10 analogue ameliorates dysfunction of the mitochondrial respiratory chain in a mouse model of Angelman syndrome.

    PubMed

    Llewellyn, Katrina J; Nalbandian, Angèle; Gomez, Arianna; Wei, Don; Walker, Naomi; Kimonis, Virginia E

    2015-04-01

    Genetic defects in the UBE3A gene, which encodes for the imprinted E6-AP ubiquitin E3 ligase (UBE3A), is responsible for the occurrence of Angelman syndrome (AS), a neurodegenerative disorder which arises in 1 out of every 12,000-20,000 births. Classical symptoms of AS include delayed development, impaired speech, and epileptic seizures with characteristic electroencephalography (EEG) readings. We have previously reported impaired mitochondrial structure and reduced complex III in the hippocampus and cerebellum in the Ube3a(m-/p+) mice. CoQ10 supplementation restores the electron flow to the mitochondrial respiratory chain (MRC) to ultimately increase mitochondrial antioxidant capacity. A number of recent studies with CoQ10 analogues seem promising in providing therapeutic benefit to patients with a variety of disorders. CoQ10 therapy has been reported to be safe and relatively well-tolerated at doses as high as 3000mg/day in patients with disorders of CoQ10 biosynthesis and MRC disorders. Herein, we report administration of idebenone, a potent CoQ10 analogue, to the Ube3a(m-/p+) mouse model corrects motor coordination and anxiety levels, and also improves the expression of complexes III and IV in hippocampus CA1 and CA2 neurons and cerebellum in these Ube3a(m-/p+) mice. However, treatment with idebenone illustrated no beneficial effects in the reduction of oxidative stress. To our knowledge, this is the first study to suggest an improvement in mitochondrial respiratory chain dysfunction via bioenergetics modulation with a CoQ10 analogue. These findings may further elucidate possible cellular and molecular mechanism(s) and ultimately a clinical therapeutic approach/benefit for patients with Angelman syndrome.

  6. Rationale and study design for a randomised controlled trial to reduce sedentary time in adults at risk of type 2 diabetes mellitus: project stand (Sedentary Time ANd diabetes)

    PubMed Central

    2011-01-01

    Background The rising prevalence of Type 2 Diabetes Mellitus (T2DM) is a major public health problem. There is an urgent need for effective lifestyle interventions to prevent the development of T2DM. Sedentary behaviour (sitting time) has recently been identified as a risk factor for diabetes, often independent of the time spent in moderate-to-vigorous physical activity. Project STAND (Sedentary Time ANd Diabetes) is a study which aims to reduce sedentary behaviour in younger adults at high risk of T2DM. Methods/Design A reduction in sedentary time is targeted using theory driven group structured education. The STAND programme is subject to piloting and process evaluation in line with the MRC framework for complex interventions. Participants are encouraged to self-monitor and self-regulate their behaviour. The intervention is being assessed in a randomised controlled trial with 12 month follow up. Inclusion criteria are a) aged 18-40 years with a BMI in the obese range; b) 18-40 years with a BMI in the overweight range plus an additional risk factor for T2DM. Participants are randomised to the intervention (n = 89) or control (n = 89) arm. The primary outcome is a reduction in sedentary behaviour at 12 months as measured by an accelerometer (count < 100/min). Secondary outcomes include physical activity, sitting/lying time using the ActivPAL posture monitor, fasting and 2 h oral glucose tolerance test, lipids, inflammatory biomarkers, body weight, waist circumference, blood pressure, illness perceptions, and efficacy beliefs for behaviour change. Conclusions This is the first UK trial to address sedentary behaviour change in a population of younger adults at risk of T2DM. The results will provide a platform for the development of a range of future multidisciplinary interventions in this rapidly expanding high-risk population. Trial registration Current controlled trials ISRCTN08434554, MRC project 91409. PMID:22151909

  7. Characterizing the mechanism of thiazolidinedione-induced hepatotoxicity: An in vitro model in mitochondria

    SciTech Connect

    Hu, Dan; Wu, Chun-qi; Li, Ze-jun; Liu, Yue; Fan, Xing; Wang, Quan-jun; Ding, Ri-gao

    2015-04-15

    Objective: To characterize the mechanism of action of thiazolidinedione (TZD)-induced liver mitochondrial toxicity caused by troglitazone, rosiglitazone, and pioglitazone in HepaRG cells. Methods: Human hepatoma cells (HepaRG) were treated with troglitazone, rosiglitazone, or pioglitazone (12.5, 25, and 50 μM) for 48 h. The Seahorse Biosciences XF24 Flux Analyzer was used to measure mitochondrial oxygen consumption. The effect of TZDs on reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected by flow cytometry. The mitochondrial ultrastructure of HepaRG cells was observed under a transmission electrical microscope (TEM). mtDNA content was evaluated by real-time PCR, and ATP content and mitochondrial respiratory chain (MRC) complex I, II, III, IV activity were measured via chemiluminescence. Results were considered statistically significant at p < 0.05. Results: Among the three drugs, troglitazone exhibited the highest potency, followed by rosiglitazone, and then pioglitazone. The TZDs caused varying degrees of mitochondrial respiratory function disorders including decreases in oxygen consumption, MRC activity, and ATP level, and an elevation in ROS level. TZD treatment resulted in mtDNA content decline, reduction in MMP, and alterations of mitochondrial structure. Conclusion: All investigated TZDs show a certain degree of mitochondrial toxicity, with troglitazone exhibiting the highest potency. The underlying mechanism of TZD-induced hepatotoxicity may be associated with alterations in mitochondrial respiratory function disorders, oxidative stress, and changes in membrane permeability. These parameters may be used early in drug development to further optimize risk:benefit profiles. - Highlights: • We compared three TZD mitochondrial toxicity characteristics in HepaRG cells. • TZD induced respiratory disorders and mitochondrial structural damage. • Mitochondrial toxicity evaluation presents guidance value for hepatotoxicity.

  8. Low immunogenicity of allogeneic human umbilical cord blood-derived mesenchymal stem cells in vitro and in vivo

    SciTech Connect

    Lee, Miyoung; Jeong, Sang Young; Ha, Jueun; Kim, Miyeon; Jin, Hye Jin; Kwon, Soon-Jae; Chang, Jong Wook; Choi, Soo Jin; Oh, Wonil; Yang, Yoon Sun; Kim, Jae-Sung; Jeon, Hong Bae

    2014-04-18

    Highlights: • hUCB-MSCs maintained low immunogenicity even after immune challenge in vitro. • Humanized NSG mice were established using human UCB CD34+ cells. • Repeated intravenous hUCB-MSC injection into mice did not lead to immune responses and adverse events. • Allogeneic hUCB-MSCs maintained low immunogenicity in vitro and in vivo. - Abstract: Evaluation of the immunogenicity of human mesenchymal stem cells (MSCs) in an allogeneic setting during therapy has been hampered by lack of suitable models due to technical and ethical limitations. Here, we show that allogeneic human umbilical cord blood derived-MSCs (hUCB-MSCs) maintained low immunogenicity even after immune challenge in vitro. To confirm these properties in vivo, a humanized mouse model was established by injecting isolated hUCB-derived CD34+ cells intravenously into immunocompromised NOD/SCID IL2γnull (NSG) mice. After repeated intravenous injection of human peripheral blood mononuclear cells (hPBMCs) or MRC5 cells into these mice, immunological alterations including T cell proliferation and increased IFN-γ, TNF-α, and human IgG levels, were observed. In contrast, hUCB-MSC injection did not elicit these responses. While lymphocyte infiltration in the lung and small intestine and reduced survival rates were observed after hPBMC or MRC5 transplantation, no adverse events were observed following hUCB-MSC introduction. In conclusion, our data suggest that allogeneic hUCB-MSCs have low immunogenicity in vitro and in vivo, and are therefore “immunologically safe” for use in allogeneic clinical applications.

  9. Phosphoprotein profiles of candidate markers for early cellular responses to low-dose γ-radiation in normal human fibroblast cells.

    PubMed

    Yim, Ji-Hye; Yun, Jung Mi; Kim, Ji Young; Lee, In Kyung; Nam, Seon Young; Kim, Cha Soon

    2017-01-24

    Ionizing radiation causes biological damage that leads to severe health effects. However, the effects and subsequent health implications caused by exposure to low-dose radiation are unclear. The objective of this study was to determine phosphoprotein profiles in normal human fibroblast cell lines in response to low-dose and high-dose γ-radiation. We examined the cellular response in MRC-5 cells 0.5 h after exposure to 0.05 or 2 Gy. Using 1318 antibodies by antibody array, we observed ≥1.3-fold increases in a number of identified phosphoproteins in cells subjected to low-dose (0.05 Gy) and high-dose (2 Gy) radiation, suggesting that both radiation levels stimulate distinct signaling pathways. Low-dose radiation induced nucleic acid-binding transcription factor activity, developmental processes, and multicellular organismal processes. By contrast, high-dose radiation stimulated apoptotic processes, cell adhesion and regulation, and cellular organization and biogenesis. We found that phospho-BTK (Tyr550) and phospho-Gab2 (Tyr643) protein levels at 0.5 h after treatment were higher in cells subjected to low-dose radiation than in cells treated with high-dose radiation. We also determined that the phosphorylation of BTK and Gab2 in response to ionizing radiation was regulated in a dose-dependent manner in MRC-5 and NHDF cells. Our study provides new insights into the biological responses to low-dose γ-radiation and identifies potential candidate markers for monitoring exposure to low-dose ionizing radiation.

  10. Physical frailty and pulmonary rehabilitation in COPD: a prospective cohort study

    PubMed Central

    Maddocks, Matthew; Kon, Samantha S C; Canavan, Jane L; Jones, Sarah E; Nolan, Claire M; Labey, Alex; Polkey, Michael I; Man, William D-C

    2016-01-01

    Background Frailty is an important clinical syndrome that is consistently associated with adverse outcomes in older people. The relevance of frailty to chronic respiratory disease and its management is unknown. Objectives To determine the prevalence of frailty among patients with stable COPD and examine whether frailty affects completion and outcomes of pulmonary rehabilitation. Methods 816 outpatients with COPD (mean (SD) age 70 (10) years, FEV1% predicted 48.9 (21.0)) were recruited between November 2011 and January 2015. Frailty was assessed using the Fried criteria (weight loss, exhaustion, low physical activity, slowness and weakness) before and after pulmonary rehabilitation. Predictors of programme non-completion were identified using multivariate logistic regression, and outcomes were compared using analysis of covariance, adjusting for age and sex. Results 209/816 patients (25.6%, 95% CI 22.7 to 28.7) were frail. Prevalence of frailty increased with age, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage, Medical Research Council (MRC) score and age-adjusted comorbidity burden (all p≤0.01). Patients who were frail had double the odds of programme non-completion (adjusted OR 2.20, 95% CI 1.39 to 3.46, p=0.001), often due to exacerbation and/or hospital admission. However, rehabilitation outcomes favoured frail completers, with consistently better responses in MRC score, exercise performance, physical activity level and health status (all p<0.001). After rehabilitation, 71/115 (61.3%) previously frail patients no longer met case criteria for frailty. Conclusions Frailty affects one in four patients with COPD referred for pulmonary rehabilitation and is an independent predictor of programme non-completion. However, patients who are frail respond favourably to rehabilitation and their frailty can be reversed in the short term. PMID:27293209

  11. Comprehensive out-patient pulmonary rehabilitation: Treatment outcomes in early and late stages of chronic obstructive pulmonary disease

    PubMed Central

    Ergün, Pinar; Kaymaz, Dicle; Günay, Ersin; Erdoğan, Yurdanur; Turay, Ülkü Yilmaz; Demir, Neşe; Çanak, Ebru; Sengül, Fatma; Egesel, Nurcan; Köse, Serdal Kenan

    2011-01-01

    BACKGROUND: The aim was to evaluate the outcomes of a comprehensive pulmonary rehabilitation (PR) in chronic obstructive pulmonary disease (COPD) and to establish whether in early disease stage PR is as effective as in late stages of disease. METHODS: A total of 55 stable COPD patients, 28 with early and 27 with late disease stages, were assessed. Patients underwent a comprehensive out-patient PR program for 8 weeks. To eluciate the effects of PR and compare the level of improvement; lung function, dyspnea sensation [Medical Research Council (MRC)], body composition [body mass index (BMI), fat free mass (FFM), fat free mass index (FFMI)], exercise capacity [incremental shuttle walking test, endurance shuttle walking test], health related quality of life (HRQoL) with St. George Respiratory Disease Questionnaire, psycohological status (Hospital anxiety–depression (HAD) scale) were evaluated before and after PR. RESULTS: At the end of PR in the early disease stage group, the improvement in forced vital capacity (FVC) reached a statistically significant level (P < 0.05). In both disease stages, there were no significant differences in BMI, FFM, and FFMI. The decrease in exertional dyspnea for the two groups evaluated with the modified BORG scale were not found statistically significant, though the dyspnea scores evaluated with MRC showed significant improvements (P < 0.001). HRQoL and exercise capacity were significantly improved for the two groups (P < 0.001). Psychological status evaluated with the HAD scale improved after PR (P < 0.001) both in early and late stages. Gainings in the study parameters did not differ in the early and the late disease stages. CONCLUSIONS: These results showed that patients with COPD had benefited from a comprehensive PR program in an out-patient setting regardless of disease severity. Even patients with earlier stage of disease should be referred and encouraged to participate in a PR program. PMID:21572695

  12. Selenoprotein H Suppresses Cellular Senescence through Genome Maintenance and Redox Regulation*

    PubMed Central

    Wu, Ryan T. Y.; Cao, Lei; Chen, Benjamin P. C.; Cheng, Wen-Hsing

    2014-01-01

    Oxidative stress and persistent DNA damage response contribute to cellular senescence, a degeneration process critically involving ataxia telangiectasia-mutated (ATM) and p53. Selenoprotein H (SelH), a nuclear selenoprotein, is proposed to carry redox and transactivation domains. To determine the role of SelH in genome maintenance, shRNA knockdown was employed in human normal and immortalized cell lines. SelH shRNA MRC-5 diploid fibroblasts under ambient O2 displayed a distinct profile of senescence including β-galactosidase expression, autofluorescence, growth inhibition, and ATM pathway activation. Such senescence phenotypes were alleviated in the presence of ATM kinase inhibitors, by p53 shRNA knockdown, or by maintaining the cells under 3% O2. During the course of 5-day recovery, the induction of phospho-ATM on Ser-1981 and γH2AX by H2O2 treatment (20 μm) subsided in scrambled shRNA but exacerbated in SelH shRNA MRC-5 cells. Results from clonogenic assays demonstrated hypersensitivity of SelH shRNA HeLa cells to paraquat and H2O2, but not to hydroxyurea, neocarzinostatin, or camptothecin. While SelH mRNA expression was induced by H2O2 treatment, SelH-GFP did not mobilize to sites of oxidative DNA damage. The glutathione level was lower in SelH shRNA than scrambled shRNA HeLa cells, and the H2O2-induced cell death was rescued in the presence of N-acetylcysteine, a glutathione precursor. Altogether, SelH protects against cellular senescence to oxidative stress through a genome maintenance pathway involving ATM and p53. PMID:25336634

  13. Synthesis and Antibacterial Evaluation of a New Series of N-Alkyl-2-alkynyl/(E)-alkenyl-4-(1H)-quinolones

    PubMed Central

    Wube, Abraham; Guzman, Juan-David; Hüfner, Antje; Hochfellner, Christina; Blunder, Martina; Bauer, Rudolf; Gibbons, Simon; Bhakta, Sanjib; Bucar, Franz

    2012-01-01

    To gain further insight into the structural requirements of the aliphatic group at position 2 for their antimycobacterial activity, some N-alkyl-4-(1H)-quinolones bearing position 2 alkynyls with various chain length and triple bond positions were prepared and tested for in vitro antibacterial activity against rapidly-growing strains of mycobacteria, the vaccine strain Mycobacterium bovis BCG, and methicillin-resistant Staphylococcus aureus strains, EMRSA-15 and -16. The compounds were also evaluated for inhibition of ATP-dependent MurE ligase of Mycobacterium tuberculosis. The lowest MIC value of 0.5 mg/L (1.2-1.5 μM) was found against M. fortuitum and M. smegmatis. These compounds displayed no or only weak toxicity to the human lung fibroblast cell line MRC-5 at 100 μM concentration. The quinolone derivatives exhibited pronounced activity against the epidemic MRSA strains (EMRSA-15 and -16) with MIC values of 2-128 mg/L (5.3-364.7 μM), and M. bovis BCG with an MIC value of 25 mg/L (66.0-77.4 μM). In addition, the compounds inhibited the MurE ligase of M. tuberculosis with moderate to weak activity showing IC50 values of 200-774 μM. The increased selectivity towards mycobacterial bacilli with reference to MRC-5 cells observed for 2-alkynyl quinolones compared to their corresponding 2-alkenyl analogues serves to highlight the mycobacterial specific effect of the triple bond. Exploration of a terminal bromine atom at the side chain of N-alkyl-2-(E)-alkenyl-4-(1H)-quinolones showed improved antimycobacterial activity whereas a cyclopropyl residue at N-1 was suggested to be detrimental to antibacterial activity. PMID:22777190

  14. Enzymatic analysis of venom from Cuban scorpion Rhopalurus junceus

    PubMed Central

    Díaz-García, Alexis; Ruiz-Fuentes, Jenny Laura; Yglesias-Rivera, Arianna; Rodríguez-Sánchez, Hermis; Riquenes Garlobo, Yanelis; Fleitas Martinez, Osmel; Fraga Castro, José A

    2015-01-01

    Rhopalurus junceus scorpion venom has been identified as a natural extract with anticancer potential. Interestingly, this scorpion venom does not cause adverse symptoms in humans. However, there is scarce information about its composition and enzymatic activity. In this work, we determined the electrophoretic profile of the venom, the gelatinase and caseinolytic activity, and the phospholipase A2 (PLA2) and hemolytic activity. The effect of different venom doses (6.25, 12.5 and 25 mg/kg) on gastrocnemius muscle was also measured as CK and LDH activity in serum. The presence of hyaluronidase was determined by turbidimetric assay. The effect of different fractions obtained by gel filtration chromatography were evaluated at different concentrations (0.05, 0.1, 0.2, 0.4, 0.6mg/ml) against lung cancer cell A549 and lung normal cell MRC-5 using MTT assay. The electrophoretic profile demonstrated the presence of proteins bands around 67kDa, 43kDa, 18.4kDa and a majority band below 14.3kDa. The venom did not showed caseinolytic, gelatinase, PLA2 and hemolytic activity even at highest venom concentration used in the study. Scorpion venom only showed a significant toxic effect on gastrocnemius muscles identified by CK and LDH release after subcutaneous injection of 12.5 and 25mg/kg. Low molecular weight fractions (<4kDa) induced a significant cytotoxicity in A549 cells while high molecular weight proteins (45–60kDa) were responsible for hyaluronidase activity and toxic effect against MRC-5. Experiments indicate that Rhopalurus junceus scorpion venom has low enzymatic activity, which could contribute to the low toxic potential of this scorpion venom. PMID:26605039

  15. Resistin-like molecule-β (RELM-β) targets airways fibroblasts to effect remodelling in asthma: from mouse to man

    PubMed Central

    Sharma, S.; Kierstein, S.; Wu, H. F.; Eid, G.; Haczku, A.; Corrigan, C. J.; Ying, S.

    2016-01-01

    Summary Background RELM-β has been implicated in airways inflammation and remodelling in murine models. Its possible functions in human airways are largely unknown. The aim was to address the hypothesis that RELM-β plays a role in extracellular matrix deposition in asthmatic airways. Methods The effects of RELM-β gene deficiency were studied in a model of allergen exposure in mice sensitised and challenged with Aspergillus fumigatus (Af). RELM-β expression was investigated in bronchial biopsies from asthmatic patients. Direct regulatory effects of RELM-β on human lung fibroblasts were examined using primary cultures and the MRC5 cell line in vitro. Results Sensitisation and challenge of wild-type mice with Af-induced release of RELM-β with a time course coincident with that of procollagen in the airways. Af-induced expression of mRNA encoding some, but not all ECM in the lung parenchyma was attenuated in RELM-β−/− mice. RELM-β expression was significantly increased in the bronchial submucosa of human asthmatics compared with controls, and its expression correlated positively with that of fibronectin and α-smooth muscle actin. In addition to epithelial cells, macrophages, fibroblasts and vascular endothelial cells formed the majority of cells expressing RELM-β in the submucosa. Exposure to RELM-β increased TGF-β1, TGF-β2, collagen I, fibronectin, smooth muscle α-actin, laminin α1, and hyaluronan and proteoglycan link protein 1 (Hapl1) production as well as proliferation by human lung fibroblasts in vitro. These changes were associated with activation of ERK1/2 in MRC5 cells. Conclusion The data are consistent with the hypothesis that elevated RELM-β expression in asthmatic airways contributes to airways remodelling at least partly by increasing fibroblast proliferation and differentiation with resulting deposition of extracellular matrix proteins. PMID:25545115

  16. Repair of multiple cervical root avulsion with sural nerve graft.

    PubMed

    Hsu, Sanford P C; Shih, Yang-Hsin; Huang, Ming-Chao; Chuang, Tien-Yow; Huang, Wen-Cheng; Wu, Hsiu-Mei; Lin, Pei-Hsin; Lee, Liang-Shong; Cheng, Henrich

    2004-09-01

    To obtain easier access to avulsed roots in the intradural space for patients suffering cervical root avulsion, the authors of this study developed a novel repair method. This involves using nerve grafts to bridge corresponding segments of the spinal cord and the trunk or cord level of the plexus, respectively, in two surgical stages. All eight patients admitted to this study received pre- and post-operative workups of electrophysiological evaluations and muscle power grading through Medical Research Council (MRC) scores. The degrees of impairment were also graded according to a modified version of Dumitru's and Wilbourn's scale (mild = 1; moderate = 2; severe = 3). The preoperative versus post-operative differences in the severity of the injuries and in the grading of the target muscle power were calculated according to the Wilcoxon signed-rank test. The preoperative degree of the severity of the injuries, as measured by electromyography (EMG), was 3.00 +/- 0.00 (mean +/- S.D.). The post-operative result was 2.125 +/- 0.641. Significant change took place after repair (P = 0.0313). Moreover, although little improvement was observed in the triceps, brachioradialis (BR), extensor carpi radialis (ECR), flexor digitorum profundus (FDP) and intrinsic hand muscles, the MRC grading showed significant yet not prominent motor recovery in the deltoid and biceps brachii (both P = 0.0313). We were impressed that the initial significant statistical results of differences in pre- and post-operative severity of the injuries and muscle power grading, demonstrated that regeneration does occur with this repair strategy.

  17. Early postnatal maternal separation causes alterations in the expression of β3-adrenergic receptor in rat adipose tissue suggesting long-term influence on obesity

    SciTech Connect

    Miki, Takanori; Liu, Jun-Qian; Ohta, Ken-ichi; Suzuki, Shingo; Kusaka, Takashi; Warita, Katsuhiko; Yokoyama, Toshifumi; Jamal, Mostofa; Ueki, Masaaki; Yakura, Tomiko; Tamai, Motoki; Sumitani, Kazunori; Hosomi, Naohisa; Takeuchi, Yoshiki

    2013-12-06

    Highlights: •High-fat diet intake following maternal separation did not cause body weight gain. •However, levels of metabolism-related molecules in adipose tissue were altered. •Increased levels of prohibitin mRNA in white fat were observed. •Attenuated levels of β3-adrenergic receptor mRNA were observed in brown fat. •Such alterations in adipose tissue may contribute to obesity later in life. -- Abstract: The effects of early postnatal maternal deprivation on the biological characteristics of the adipose tissue later in life were investigated in the present study. Sprague–Dawley rats were classified as either maternal deprivation (MD) or mother-reared control (MRC) groups. MD was achieved by separating the rat pups from their mothers for 3 h each day during the 10–15 postnatal days. mRNA levels of mitochondrial uncoupling protein 1 (UCP-1), β3-adrenergic receptor (β3-AR), and prohibitin (PHB) in the brown and white adipose tissue were determined using real-time RT-PCR analysis. UCP-1, which is mediated through β3-AR, is closely involved in the energy metabolism and expenditure. PHB is highly expressed in the proliferating tissues/cells. At 10 weeks of age, the body weight of the MRC and MD rats was similar. However, the levels of the key molecules in the adipose tissue were substantially altered. There was a significant increase in the expression of PHB mRNA in the white adipose tissue, while the β3-AR mRNA expression decreased significantly, and the UCP-1 mRNA expression remained unchanged in the brown adipose tissue. Given that these molecules influence the mitochondrial metabolism, our study indicates that early postnatal maternal deprivation can influence the fate of adipose tissue proliferation, presumably leading to obesity later in life.

  18. Feature long axis size and local luminance contrast determine ship target acquisition performance: strong evidence for the TOD case

    NASA Astrophysics Data System (ADS)

    Bijl, Piet; Toet, Alexander; Kooi, Frank L.

    2016-10-01

    Visual images of a civilian target ship on a sea background were produced using a CAD model. The total set consisted of 264 images and included 3 different color schemes, 2 ship viewing aspects, 5 sun illumination conditions, 2 sea reflection values, 2 ship positions with respect to the horizon and 3 values of atmospheric contrast reduction. In a perception experiment, the images were presented on a display in a long darkened corridor. Observers were asked to indicate the range at which they were able to detect the ship and classify the following 5 ship elements: accommodation, funnel, hull, mast, and hat above the bridge. This resulted in a total of 1584 Target Acquisition (TA) range estimates for two observers. Next, the ship contour, ship elements and corresponding TA ranges were analyzed applying several feature size and contrast measures. Most data coincide on a contrast versus angular size plot using (1) the long axis as characteristic ship/ship feature size and (2) local Weber contrast as characteristic ship/ship feature contrast. Finally, the data were compared with a variety of visual performance functions assumed to be representative for Target Acquisition: the TOD (Triangle Orientation Discrimination), MRC (Minimum Resolvable Contrast), CTF (Contrast Threshold Function), TTP (Targeting Task Performance) metric and circular disc detection data for the unaided eye (Blackwell). The results provide strong evidence for the TOD case: both position and slope of the TOD curve match the ship detection and classification data without any free parameter. In contrast, the MRC and CTF are too steep, the TTP and disc detection curves are too shallow and all these curves need an overall scaling factor in order to coincide with the ship and ship feature recognition data.

  19. Basic fibroblast growth factor activates β-catenin/RhoA signaling in pulmonary fibroblasts with chronic obstructive pulmonary disease in rats.

    PubMed

    Ge, Zhengxing; Li, Bo; Zhou, Xun; Yang, Yi; Zhang, Jun

    2016-12-01

    Chronic obstructive pulmonary disease (COPD) is featured by aberrant extracellular matrix (ECM) deposition. Trigger of the β-catenin/RhoA pathway has been involved in aberrant ECM deposition in several diseases. We investigated WNT signaling activation in primary pulmonary fibroblasts of rats with and without COPD and the function of WNT signaling in pulmonary fibroblast. We evaluated the expression of WNT signaling and the role of β-catenin, using MRC-5 fibroblasts and primary lung fibroblasts of rats with and without COPD. Lung fibroblasts highly expressed mRNA of genes associated with WNT signaling. Treatment of MRC-5 fibroblasts using basic fibroblast growth factor (bFGF), a composition of the mucus in COPD patients, enhanced β-catenin, Wnt5a and RhoA expression. The expression in β-catenin, Wnt5a and RhoA induced by bFGF was higher in fibroblasts of rats with COPD than without COPD, whereas the basal expression was similar. bFGF also activated transcriptionally active and increased total β-catenin protein expression. Moreover, bFGF enhanced the expression of α-sm-actin and fibronectin, which was abrogated by β-catenin, Wnt5a and RhoA-specific adenovirus siRNA. The induction of active β-catenin and then fibronectin turnover in response to bFGF were markedly increased in pulmonary fibroblasts from rat with COPD. β-Catenin/RhoA pathway results in ECM deposition in lung fibroblasts and myofibroblasts differentiation. β-catenin/RhoA signaling induced by bFGF is promoted in lung fibroblasts from rats with COPD. The study indicated a crucial role of the WNT signaling in mediating fibroblast morphology and function in COPD.

  20. Characteristics of Patients with Chronic Obstructive Pulmonary Disease at the First Visit to a Pulmonary Medical Center in Korea: The KOrea COpd Subgroup Study Team Cohort.

    PubMed

    Lee, Jung Yeon; Chon, Gyu Rak; Rhee, Chin Kook; Kim, Deog Kyeom; Yoon, Hyoung Kyu; Lee, Jin Hwa; Yoo, Kwang Ha; Lee, Sang Haak; Lee, Sang Yeub; Kim, Tae-Eun; Kim, Tae-Hyung; Park, Yong Bum; Hwang, Yong Il; Kim, Young Sam; Jung, Ki Suck

    2016-04-01

    The Korea Chronic Obstructive Pulmonary Disorders Subgroup Study Team (Korea COPD Subgroup Study team, KOCOSS) is a multicenter observational study that includes 956 patients (mean age 69.9 ± 7.8 years) who were enrolled from 45 tertiary and university-affiliated hospitals from December 2011 to October 2014. The initial evaluation for all patients included pulmonary function tests (PFT), 6-minute walk distance (6MWD), COPD Assessment Test (CAT), modified Medical Research Council (mMRC) dyspnea scale, and the COPD-specific version of St. George's Respiratory Questionnaire (SGRQ-C). Here, we report the comparison of baseline characteristics between patients with early- (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage I and II/groups A and B) and late-stage COPD (GOLD stage III and IV/groups C and D). Among all patients, the mean post-bronchodilator FEV1 was 55.8% ± 16.7% of the predicted value, and most of the patients were in GOLD stage II (520, 56.9%) and group B (399, 42.0%). The number of exacerbations during one year prior to the first visit was significantly lower in patients with early COPD (0.4 vs. 0.9/0.1 vs. 1.2), as were the CAT score (13.9 vs. 18.3/13.5 vs. 18.1), mMRC (1.4 vs. 2.0/1.3 vs.1.9), and SGRQ-C total score (30.4 vs. 42.9/29.1 vs. 42.6) compared to late-stage COPD (all P < 0.001). Common comorbidities among all patients were hypertension (323, 37.7%), diabetes mellitus (139, 14.8%), and depression (207, 23.6%). The data from patients with early COPD will provide important information towards early detection, proper initial management, and design of future studies.

  1. Autosomal-recessive cerebellar ataxia caused by a novel ADCK3 mutation that elongates the protein: clinical, genetic and biochemical characterisation

    PubMed Central

    Liu, Yo-Tsen; Hersheson, Joshua; Plagnol, Vincent; Fawcett, Katherine; Duberley, Kate E C; Preza, Elisavet; Hargreaves, Iain P; Chalasani, Annapurna; Laurá, Matilde; Wood, Nick W; Reilly, Mary M; Houlden, Henry

    2014-01-01

    Background The autosomal-recessive cerebellar ataxias (ARCA) are a clinically and genetically heterogeneous group of neurodegenerative disorders. The large number of ARCA genes leads to delay and difficulties obtaining an exact diagnosis in many patients and families. Ubiquinone (CoQ10) deficiency is one of the potentially treatable causes of ARCAs as some patients respond to CoQ10 supplementation. The AarF domain containing kinase 3 gene (ADCK3) is one of several genes associated with CoQ10 deficiency. ADCK3 encodes a mitochondrial protein which functions as an electron-transfer membrane protein complex in the mitochondrial respiratory chain (MRC). Methods We report two siblings from a consanguineous Pakistani family who presented with cerebellar ataxia and severe myoclonus from adolescence. Whole exome sequencing and biochemical assessment of fibroblasts were performed in the index patient. Results A novel homozygous frameshift mutation in ADCK3 (p.Ser616Leufs*114), was identified in both siblings. This frameshift mutation results in the loss of the stop codon, extending the coding protein by 81 amino acids. Significant CoQ10 deficiency and reduced MRC enzyme activities in the index patient's fibroblasts suggested that the mutant protein may reduce the efficiency of mitochondrial electron transfer. CoQ10 supplementation was initiated following these genetic and biochemical analyses. She gained substantial improvement in myoclonic movements, ataxic gait and dysarthric speech after treatment. Conclusion This study highlights the importance of diagnosing ADCK3 mutations and the potential benefit of treatment for patients. The identification of this new mutation broadens the phenotypic spectrum associated with ADCK3 mutations and provides further understanding of their pathogenic mechanism. PMID:24218524

  2. A complex postnatal mental health intervention: Australian translational formative evaluation.

    PubMed

    Rowe, Heather J; Wynter, Karen H; Burns, Joanna K; Fisher, Jane R W

    2016-01-07

    Reducing the burden of postnatal maternal mental health problems is an international public health priority. We developed What Were We Thinking (WWWT), a psychoeducation programme for primary postnatal health care that addresses known but neglected risks. We then demonstrated evidence of its effects in a before-and-after controlled study in preventing maternal postnatal mental health problems among women without a psychiatric history participating in the intervention compared to usual care (AOR 0.43; 95% CI 0.21, 0.89) when conducted by specialist nurses. Testing its effectiveness when implemented in routine primary care requires changes at practitioner, organizational and health system levels. This paper describes a programme of translational formative evaluation to inform the protocol for a cluster RCT. Following the UK Medical Research Council (MRC) Guidance for evaluating complex interventions, we conducted a translational formative evaluation using mixed methods. Collection and analysis of postnatal health service documents, semi-structured interviews, group discussions and an online survey were used to investigate service provision, consumers' needs and expectations, clinicians' attitudes and clinical practice, and the implications for health service delivery. Participants were expectant parents, health care providers, health service managers and government policy makers. Results documented current clinical practice, staff training needs, necessary service modifications to standardize advice to parents and include fathers, key priorities and drivers of government health policy, and informed a model of costs and expected health and social outcomes. Implementation of WWWT into routine postnatal care requires adjustments to clinical practice. Staff training, modifications to service opening hours and economic implications for the health system also need to be considered. The MRC Guidance for developing and evaluating complex interventions is a useful framework

  3. Reliability of the Brazilian Portuguese version of the fatigue severity scale and its correlation with pulmonary function, dyspnea, and functional capacity in patients with COPD*

    PubMed Central

    Valderramas, Silvia; Camelier, Aquiles Assunção; da Silva, Sinara Alves; Mallmann, Renata; de Paulo, Hanna Karine; Rosa, Fernanda Warken

    2013-01-01

    OBJECTIVE: To describe the intra-rater and inter-rater reliability of the Brazilian Portuguese version of the fatigue severity scale (FSS) in patients with COPD and to identify the presence of its association with parameters of pulmonary function, dyspnea, and functional capacity. METHODS: This was an observational cross-sectional study involving 50 patients with COPD, who completed the FSS in interviews with two researchers in two visits. The FSS scores were correlated with those of the Medical Research Council (MRC) scale, as well as with FEV1, FVC, and six-minute walk distance (6MWD). RESULTS: The mean age of the patients was 69.4 ± 8.23 years, whereas the mean FEV1 was 46.5 ± 20.4% of the predicted value. The scale was reliable, with an intraclass correlation coefficient of 0.90 (95% CI, 0.81-0.94; p < 0.01). The FSS scores showed significant correlations with those of MRC scale (r = 0.70; p < 0.01), as well as with 6MWD (r = –0.77; p < 0.01), FEV1 (r = –0.38; p < 0.01), FVC (r = –0.35; p < 0.01), and stage of the disease in accordance with the Global Initiative for Chronic Obstructive Lung Disease criteria (r = 0.37; p < 0.01). CONCLUSIONS: The Brazilian Portuguese version of the FSS proved reliable for use in COPD patients in Brazil and showed significant correlations with sensation of dyspnea, functional capacity, pulmonary function, and stage of the disease. PMID:24068263

  4. Human cytomegalovirus gene UL21a encodes a short-lived cytoplasmic protein and facilitates virus replication in fibroblasts.

    PubMed

    Fehr, Anthony R; Yu, Dong

    2010-01-01

    The human cytomegalovirus (HCMV) gene UL21a was recently annotated by its conservation in chimpanzee cytomegalovirus. Two large-scale mutagenic analyses showed that mutations in overlapping UL21a/UL21 resulted in a severe defect of virus growth in fibroblasts. Here, we characterized UL21a and demonstrated its role in HCMV infection. We mapped a UL21a-specific transcript of approximately 600 bp that was expressed with early kinetics. UL21a encoded pUL21a, a protein of approximately 15 kDa, which was unstable and localized predominantly to the cytoplasm during HCMV infection or when expressed alone. Interestingly, pUL21a was drastically stabilized in the presence of proteasome inhibitor MG132, but its instability was independent of a functional ubiquitin-mediated pathway, suggesting that pUL21a underwent proteasome-dependent, ubiquitin-independent degradation. A UL21a deletion virus was attenuated in primary human newborn foreskin fibroblasts (HFFs) and embryonic lung fibroblasts (MRC-5), whereas a marker-rescued virus and mutant viruses lacking the neighboring or overlapping genes UL20, UL21, or UL21.5-UL23 replicated at wild-type levels. The growth defect of UL21a-deficient virus in MRC-5 cells was more pronounced than that in HFFs. At a high multiplicity of infection, the UL21a deletion virus synthesized viral proteins with wild-type kinetics but had a two- to threefold defect in viral DNA replication. More importantly, although pUL21a was not detected in the virion, progeny virions produced by the mutant virus were approximately 10 times less infectious than wild-type virus, suggesting that UL21a is required for HCMV to establish efficient productive infection. We conclude that UL21a encodes a short-lived cytoplasmic protein and facilitates HCMV replication in fibroblasts.

  5. Living donor liver transplantation using grafts with hepatic cysts.

    PubMed

    Sakamoto, Seisuke; Nosaka, Shunsuke; Shigeta, Takanobu; Uchida, Hajime; Hamano, Ikumi; Karaki, Chiaki; Kanazawa, Hiroyuki; Fukuda, Akinari; Nakazawa, Atsuko; Kasahara, Mureo

    2012-12-01

    Cystic lesions in the liver are often found through the evaluation of liver donors. Multiple cysts are worrisome, and donor candidates with multiple cysts may be unacceptable as liver donors, especially when their recipients have fibrocystic disease (FCD), which is an inherited disorder. This study reviewed 183 cases of living donor liver transplantation. We collected clinical and radiological data associated with donors with cystic lesions and with donors without cystic lesions, and we evaluated the outcomes of these donors and their recipients. As part of the preoperative radiological assessment of grafts, magnetic resonance cholangiography (MRC) was performed to evaluate the biliary anatomy of donor candidates with multiple cysts. Thirty-four donors (18.6%) had 1 or more cystic lesions in the liver, and 6 of these donors had multiple cysts (ie, >10). Donors with multiple cysts were older and heavier, and there was a significant relationship between these donors and recipients whose original disease was FCD. During the follow-up (median = 3.1 years), all donors with cystic lesions were found to be doing well without any major postoperative complications. Fifteen recipients who received grafts with cystic lesions (12 left-sided lobes and 3 right-sided lobes) had no complications related to the cystic lesions. In conclusion, donors with cystic lesions may be acceptable as liver donors, although our data are limited mostly to left-sided lobe donation with a short follow-up period. MRC should be preoperatively performed to rule out any biliary anomalies, especially in donor candidates whose recipients have FCD.

  6. Comparative analyses of gene copy number and mRNA expression in GBM tumors and GBM xenografts

    SciTech Connect

    Hodgson, J. Graeme; Yeh, Ru-Fang; Ray, Amrita; Wang, Nicholas J.; Smirnov, Ivan; Yu, Mamie; Hariono, Sujatmi; Silber, Joachim; Feiler, Heidi S.; Gray, Joe W.; Spellman, Paul T.; Vandenberg, Scott R.; Berger, Mitchel S.; James, C. David

    2009-04-03

    Development of model systems that recapitulate the molecular heterogeneity observed among glioblastoma multiforme (GBM) tumors will expedite the testing of targeted molecular therapeutic strategies for GBM treatment. In this study, we profiled DNA copy number and mRNA expression in 21 independent GBM tumor lines maintained as subcutaneous xenografts (GBMX), and compared GBMX molecular signatures to those observed in GBM clinical specimens derived from the Cancer Genome Atlas (TCGA). The predominant copy number signature in both tumor groups was defined by chromosome-7 gain/chromosome-10 loss, a poor-prognosis genetic signature. We also observed, at frequencies similar to that detected in TCGA GBM tumors, genomic amplification and overexpression of known GBM oncogenes, such as EGFR, MDM2, CDK6, and MYCN, and novel genes, including NUP107, SLC35E3, MMP1, MMP13, and DDX1. The transcriptional signature of GBMX tumors, which was stable over multiple subcutaneous passages, was defined by overexpression of genes involved in M phase, DNA replication, and chromosome organization (MRC) and was highly similar to the poor-prognosis mitosis and cell-cycle module (MCM) in GBM. Assessment of gene expression in TCGA-derived GBMs revealed overexpression of MRC cancer genes AURKB, BIRC5, CCNB1, CCNB2, CDC2, CDK2, and FOXM1, which form a transcriptional network important for G2/M progression and/or checkpoint activation. Our study supports propagation of GBM tumors as subcutaneous xenografts as a useful approach for sustaining key molecular characteristics of patient tumors, and highlights therapeutic opportunities conferred by this GBMX tumor panel for testing targeted therapeutic strategies for GBM treatment.

  7. Organochlorines and metals induce changes in the mitochondria-rich cells of fish gills: an integrative field study involving chemical, biochemical and morphological analyses.

    PubMed

    Fernandes, M N; Paulino, M G; Sakuragui, M M; Ramos, C A; Pereira, C D S; Sadauskas-Henrique, H

    2013-01-15

    Through integrating chemical, biochemical and morphological analyses, this study investigated the effects of multiple pollutants on the gill mitochondria-rich cells (MRCs) in two fish species, Astyanax fasciatus and Pimelodus maculatus, collected from five sites (FU10, FU20, FU30, FU40 and FU50) in the Furnas Hydroelectric Power Station reservoir. Water analyses revealed aluminum, iron and zinc as well as organochlorine (aldrin/dieldrin, endosulfan, heptachlor/heptachlor epoxide and metolachlor) contamination at all of the sites, with the exception of FU10. Copper, chrome, iron and zinc were detected in the gills of both species, and aldrin/dieldrin, endosulfan and heptachlor/heptachlor epoxide were detected in the gills of fish from all of the sites, with the exception of FU10. Fish collected at FU20, FU30 and FU50 exhibited numerous alterations in the surface architecture of their pavement cells and MRCs. The surface MRC density and MRC fractional area were lower in fish from FU20, FU30, FU40 and FU50 than in those from the reference site (FU10) in the winter, and some variability between the sites was observed in the summer. The organochlorine contamination at FU20 and FU50 was associated with variable changes in the MRCs and inhibition of Na(+)/K(+)-ATPase (NKA) activity, especially in P. maculatus. At FU30, the alterations in the MRCs were associated with the contaminants present, especially metals. A multivariate analysis demonstrated a positive association between the biological responses of both species and environmental contamination, indicating that under realistic conditions, a mixture of organochlorines and metals affected the MRCs by inhibiting NKA activity and inducing morphological changes, which may cause an ionic imbalance.

  8. The reliability and predictive ability of a biomarker of oxidative DNA damage on functional outcomes after stroke rehabilitation.

    PubMed

    Hsieh, Yu-Wei; Lin, Keh-Chung; Korivi, Mallikarjuna; Lee, Tsong-Hai; Wu, Ching-Yi; Wu, Kuen-Yuh

    2014-04-16

    We evaluated the reliability of 8-hydroxy-2'-deoxyguanosine (8-OHdG), and determined its ability to predict functional outcomes in stroke survivors. The rehabilitation effect on 8-OHdG and functional outcomes were also assessed. Sixty-one stroke patients received a 4-week rehabilitation. Urinary 8-OHdG levels were determined by liquid chromatography-tandem mass spectrometry. The test-retest reliability of 8-OHdG was good (interclass correlation coefficient=0.76). Upper-limb motor function and muscle power determined by the Fugl-Meyer Assessment (FMA) and Medical Research Council (MRC) scales before rehabilitation showed significant negative correlation with 8-OHdG (r=-0.38, r=-0.30; p<0.05). After rehabilitation, we found a fair and significant correlation between 8-OHdG and FMA (r=-0.34) and 8-OHdG and pain (r=0.26, p<0.05). Baseline 8-OHdG was significantly correlated with post-treatment FMA, MRC, and pain scores (r=-0.34, -0.31, and 0.25; p<0.05), indicating its ability to predict functional outcomes. 8-OHdG levels were significantly decreased, and functional outcomes were improved after rehabilitation. The exploratory study findings conclude that 8-OHdG is a reliable and promising biomarker of oxidative stress and could be a valid predictor of functional outcomes in patients. Monitoring of behavioral indicators along with biomarkers may have crucial benefits in translational stroke research.

  9. IVIDIL experiment onboard the ISS

    NASA Astrophysics Data System (ADS)

    Shevtsova, Valentina

    2010-09-01

    The experiment IVIDIL (Influence of Vibrations on Diffusion in Liquids) is scheduled to be performed in forthcoming fall 2009 onboard the ISS, inside the SODI instrument mounted in the Glovebox on the ESA Columbus module. It is planned to carry out 39 experimental runs with each of them lasting 18 h. The objective of the experiment is threefold. After each space experiment there is a discussion about the role of onboard g-jitters. One objective is to identify the limit level of vibrations below which g-jitter does not play a role for onboard experiments. This objective will be fulfilled by observing diffusive process under different imposed controlled vibrations. Second, to perform precise measurements of diffusion and thermodiffusion coefficients for two binary mixtures in the absence of buoyant convection. The measured values can be used as standards for ground experiments. Two aqueous solutions will be used as test fluids: two different concentrations of water-isopropanol (IPA) with positive and negative Soret effect. This objective also includes studying the influence of vibrations on the measured values of diffusion and thermodiffusion coefficients. Finally, to investigate vibration-induced convection and, particularly, heat and mass transfer under vibrations. Three International Teams are involved in the preparation of the experiment ( Shevtsova et al., 2007). ULB (MRC) is responsible for all aspects related to IVIDIL experimental definition, theoretical and numerical modeling and coordination of the entire project. Team from Ryerson University (led by Z. Saghir), Ontario, Canada and Russian team from Perm, ICMM UB RAS (led by T. Lyubimova) provide theoretical and numerical support. As being the coordinator, the author will present a general description of the experiment and outline some results obtained by MRC, ULB researchers only, i.e. by A. Mialdun, D. Melnikov, I. Ryzhkov, Yu. Gaponenko.

  10. Polydimethylsiloxane SlipChip for mammalian cell culture applications.

    PubMed

    Chang, Chia-Wen; Peng, Chien-Chung; Liao, Wei-Hao; Tung, Yi-Chung

    2015-11-07

    This paper reports a polydimethylsiloxane (PDMS) SlipChip for in vitro cell culture applications, multiple-treatment assays, cell co-cultures, and cytokine detection assays. The PDMS SlipChip is composed of two PDMS layers with microfluidic channels on each surface that are separated by a thin silicone fluid (Si-fluid) layer. The integration of Si-fluid enables the two PDMS layers to be slid to different positions; therefore, the channel patterns can be re-arranged for various applications. The SlipChip design significantly reduces the complexity of sample handling, transportation, and treatment processes. To apply the developed SlipChip for cell culture applications, human lung adenocarcinoma epithelial cells (A549) and lung fibroblasts (MRC-5) were cultured to examine the biocompatibility of the developed PDMS SlipChip. Moreover, embryonic pluripotent stem cells (ES-D3) were also cultured in the device to evaluate the retention of their stemness in the device. The experimental results show that cell morphology, viability and proliferation are not affected when the cells are cultured in the SlipChip, indicating that the device is highly compatible with mammalian cell culture. In addition, the stemness of the ES-D3 cells was highly retained after they were cultured in the device, suggesting the feasibility of using the SlipChip for stem cell research. Various cell experiments, such as simultaneous triple staining of cells and co-culture of MRC-5 with A549 cells, were also performed to demonstrate the functionalities of the PDMS SlipChip. Furthermore, we used a cytokine detection assay to evaluate the effect of endotoxin (lipopolysaccharides, LPS) treatment on the cytokine secretion of A549 cells using the SlipChip. The developed PDMS SlipChip provides a straightforward and effective platform for various on-chip in vitro cell cultures and consequent analysis, which is promising for a number of cell biology studies and biomedical applications.

  11. Gulf of Mexico Regional Collaborative Final Report

    SciTech Connect

    Judd, Kathleen S.; Judd, Chaeli; Engel-Cox, Jill A.; Gulbransen, Thomas; Anderson, Michael G.; Woodruff, Dana L.; Thom, Ronald M.; Guzy, Michael; Hardin, Danny; Estes, Maury

    2007-12-01

    This report presents the results of the Gulf of Mexico Regional Collaborative (GoMRC), a year-long project funded by NASA. The GoMRC project was organized around end user outreach activities, a science applications team, and a team for information technology (IT) development. Key outcomes are summarized below for each of these areas. End User Outreach; Successfully engaged federal and state end users in project planning and feedback; With end user input, defined needs and system functional requirements; Conducted demonstration to End User Advisory Committee on July 9, 2007 and presented at Gulf of Mexico Alliance (GOMA) meeting of Habitat Identification committee; Conducted significant engagement of other end user groups, such as the National Estuary Programs (NEP), in the Fall of 2007; Established partnership with SERVIR and Harmful Algal Blooms Observing System (HABSOS) programs and initiated plan to extend HABs monitoring and prediction capabilities to the southern Gulf; Established a science and technology working group with Mexican institutions centered in the State of Veracruz. Key team members include the Federal Commission for the Protection Against Sanitary Risks (COFEPRIS), the Ecological Institute (INECOL) a unit of the National Council for science and technology (CONACYT), the Veracruz Aquarium (NOAA’s first international Coastal Ecology Learning Center) and the State of Veracruz. The Mexican Navy (critical to coastal studies in the Southern Gulf) and other national and regional entities have also been engaged; and Training on use of SERVIR portal planned for Fall 2007 in Veracruz, Mexico Science Applications; Worked with regional scientists to produce conceptual models of submerged aquatic vegetation (SAV) ecosystems; Built a logical framework and tool for ontological modeling of SAV and HABs; Created online guidance for SAV restoration planning; Created model runs which link potential future land use trends, runoff and SAV viability; Analyzed SAV

  12. Exploring star formation in high-z galaxies using atomic and molecular emission lines

    NASA Astrophysics Data System (ADS)

    Gullberg, Bitten

    2016-03-01

    The conditions under which stars are formed and the reasons for triggering and quenching of starburst events in high-z galaxies, are still not well understood. Studying the interstellar medium (ISM) and the morphology of high-z galaxies are therefore key points in order to understand galaxy evolution. The cosmic star formation rate density peaks between 1>1, and low to moderate [CII] optical depth tau(CII)<1. Combining millimetre/sub-millimetre and optical data cubes for the high-z radio galaxy (HzRG) MRC0943-242, has revealed a much more complicated morphology than seen in the individual data sets. The millimetre/sub-millimetre observations data have allowed us to spatially separate of the AGN and starburst dominated components, which ~65 kpc apart. The optical data reveal structures of emitting and absorbing gas at multiple wavelengths. A deep high resolution millimetre/sub-millimetre study of the HzRG MRC1138-262, shows emission from water (H2O) and an unusually large amount of neutral atomic carbon ([CI]) relative to highly excited CO compared to lensed DSFGs. The

  13. Essential Oil of Cymbopogon nardus (L.) Rendle: A Strategy to Combat Fungal Infections Caused by Candida Species

    PubMed Central

    De Toledo, Luciani Gaspar; Ramos, Matheus Aparecido Dos Santos; Spósito, Larissa; Castilho, Elza Maria; Pavan, Fernando Rogério; Lopes, Érica De Oliveira; Zocolo, Guilherme Julião; Silva, Francisca Aliny Nunes; Soares, Tigressa Helena; dos Santos, André Gonzaga; Bauab, Taís Maria; De Almeida, Margarete Teresa Gottardo

    2016-01-01

    Background: The incidence of fungal infections, especially those caused by Candida yeasts, has increased over the last two decades. However, the indicated therapy for fungal control has limitations. Hence, medicinal plants have emerged as an alternative in the search for new antifungal agents as they present compounds, such as essential oils, with important biological effects. Published data demonstrate important pharmacological properties of the essential oil of Cymbopogon nardus (L.) Rendle; these include anti-tumor, anti-nociceptive, and antibacterial activities, and so an investigation of this compound against pathogenic fungi is interesting. Objective: The aim of this study was to evaluate the chemical composition and biological potential of essential oil (EO) obtained from the leaves of C. nardus focusing on its antifungal profile against Candida species. Methods: The EO was obtained by hydrodistillation and analyzed by gas chromatography-mass spectrometry (GC-MS). Testing of the antifungal potential against standard and clinical strains was performed by determining the minimal inhibitory concentration (MIC), time-kill, inhibition of Candida albicans hyphae growth, and inhibition of mature biofilms. Additionally, the cytotoxicity was investigated by the IC50 against HepG-2 (hepatic) and MRC-5 (fibroblast) cell lines. Results: According to the chemical analysis, the main compounds of the EO were the oxygen-containing monoterpenes: citronellal, geranial, geraniol, citronellol, and neral. The results showed important antifungal potential for all strains tested with MIC values ranging from 250 to 1000 μg/mL, except for two clinical isolates of C. tropicalis (MIC > 1000 μg/mL). The time-kill assay showed that the EO inhibited the growth of the yeast and inhibited hyphal formation of C. albicans strains at concentrations ranging from 15.8 to 1000 μg/mL. Inhibition of mature biofilms of strains of C. albicans, C. krusei and C. parapsilosis occurred at a

  14. Zinc oxide nanoparticles exhibit cytotoxicity and genotoxicity through oxidative stress responses in human lung fibroblasts and Drosophila melanogaster

    PubMed Central

    Ng, Cheng Teng; Yong, Liang Qing; Hande, Manoor Prakash; Ong, Choon Nam; Yu, Liya E; Bay, Boon Huat; Baeg, Gyeong Hun

    2017-01-01

    Background Although zinc oxide nanoparticles (ZnO NPs) have been widely used, there has been an increasing number of reports on the toxicity of ZnO NPs. However, study on the underlying mechanisms under in vivo conditions is insufficient. Methods In this study, we investigated the toxicological profiles of ZnO NPs in MRC5 human lung fibroblasts in vitro and in an in vivo model using the fruit fly Drosophila melanogaster. A comprehensive study was conducted to evaluate the uptake, cytotoxicity, reactive oxygen species (ROS) formation, gene expression profiling and genotoxicity induced by ZnO NPs. Results For in vitro toxicity, the results showed that there was a significant release of extracellular lactate dehydrogenase and decreased cell viability in ZnO NP-treated MRC5 lung cells, indicating cellular damage and cytotoxicity. Generation of ROS was observed to be related to significant expression of DNA Damage Inducible Transcript (DDIT3) and endoplasmic reticulum (ER) to nucleus signaling 1 (ERN1) genes, which are ER stress-related genes. Oxidative stress induced DNA damage was further verified by a significant release of DNA oxidation product, 8-hydroxydeoxyguanosine (8-OHdG), as well as by the Comet assay. For the in vivo study using the fruit fly D. melanogaster as a model, significant toxicity was observed in F1 progenies upon ingestion of ZnO NPs. ZnO NPs induced significant decrease in the egg-to-adult viability of the flies. We further showed that the decreased viability is closely associated with ROS induction by ZnO NPs. Removal of one copy of the D. melanogaster Nrf2 alleles further decreased the ZnO NPs-induced lethality due to increased production of ROS, indicating that nuclear factor E2-related factor 2 (Nrf2) plays important role in ZnO NPs-mediated ROS production. Conclusion The present study suggests that ZnO NPs induced significant oxidative stress-related cytotoxicity and genotoxicity in human lung fibroblasts in vitro and in D. melanogaster in

  15. Green synthesis of bacterial mediated anti-proliferative gold nanoparticles: inducing mitotic arrest (G2/M phase) and apoptosis (intrinsic pathway)

    NASA Astrophysics Data System (ADS)

    Ganesh Kumar, C.; Poornachandra, Y.; Chandrasekhar, Cheemalamarri

    2015-11-01

    The physiochemical and biological properties of microbial derived gold nanoparticles have potential applications in various biomedical domains as well as in cancer therapy. We have fabricated anti-proliferative bacterial mediated gold nanoparticles (b-Au NPs) using a culture supernatant of Streptomyces clavuligerus and later characterized them by UV-visible, TEM, DLS, XRD and FT-IR spectroscopic techniques. The capping agent responsible for the nanoparticle formation was characterized based on SDS-PAGE and MALDI-TOF-MS analyses. They were tested for anticancer activity in A549, HeLa and DU145 cell lines. The biocompatibility and non-toxic nature of the nanoparticles were tested on normal human lung cell line (MRC-5). The b-Au NPs induced the cell cycle arrest in G2/M phase and also inhibited the microtubule assembly in DU145 cells. Mechanistic studies, such as ROS, MMP, Cyt-c, GSH, caspases 9, 8 and 3 activation and the Annexin V-FITC staining, along with the above parameters tested provided sufficient evidence that the b-Au NPs induced apoptosis through the intrinsic pathway. The results supported the use of b-Au NPs for future therapeutic application in cancer therapy and other biomedical applications.The physiochemical and biological properties of microbial derived gold nanoparticles have potential applications in various biomedical domains as well as in cancer therapy. We have fabricated anti-proliferative bacterial mediated gold nanoparticles (b-Au NPs) using a culture supernatant of Streptomyces clavuligerus and later characterized them by UV-visible, TEM, DLS, XRD and FT-IR spectroscopic techniques. The capping agent responsible for the nanoparticle formation was characterized based on SDS-PAGE and MALDI-TOF-MS analyses. They were tested for anticancer activity in A549, HeLa and DU145 cell lines. The biocompatibility and non-toxic nature of the nanoparticles were tested on normal human lung cell line (MRC-5). The b-Au NPs induced the cell cycle arrest in G2

  16. Overexpression of miR-26a-2 in human liposarcoma is correlated with poor patient survival.

    PubMed

    Lee, D H; Amanat, S; Goff, C; Weiss, L M; Said, J W; Doan, N B; Sato-Otsubo, A; Ogawa, S; Forscher, C; Koeffler, H P

    2013-05-20

    Approximately 90% of well-differentiated/de-differentiated liposarcomas (WDLPS/DDLPS), the most common LPS subtype, have chromosomal amplification at 12q13-q22. Many protein-coding genes in the region, such as MDM2 and , have been studied as potential therapeutic targets for LPS treatment, with minimal success. In the amplified region near the MDM2 gene, our single nucleotide polymorphism (SNP) array analysis of 75 LPS samples identified frequent amplification of miR-26a-2. Besides being in the amplicon, miR-26a-2 was overexpressed significantly in WDLPS/DDLPS (P<0.001), as well as in myxoid/round cell LPS (MRC) (P<0.05). Furthermore, Kaplan-Meier survival analysis showed that overexpression of miR-26a-2 significantly correlated with poor patient survival in both types of LPS (P<0.05 for WDLPS/DDLPS; P<0.001 for MRC). Based on these findings, we hypothesized that miR-26a-2 has an important role in LPS tumorigenesis, regardless of LPS subtypes. Overexpression of miR-26a-2 in three LPS cell lines (SW872, LPS141 and LP6) enhanced the growth and survival of these cells, including faster cell proliferation and migration, enhanced clonogenicity, suppressed adipocyte differentiation and/or resistance to apoptosis. Inhibition of miR-26a-2 in LPS cells using anti-miR-26a-2 resulted in the opposite responses. To explain further the effect of miR-26a-2 overexpression in LPS cells, we performed in silico analysis and identified 93 candidate targets of miR-26a-2. Among these genes, RCBTB1 (regulator of chromosome condensation and BTB domain-containing protein 1) is located at 13q12.3-q14.3, a region of recurrent loss of heterozygosity (LOH) in LPS. Indeed, either overexpression or inhibition of RCBTB1 made LPS cells more susceptible or resistant to apoptosis, respectively. In conclusion, our study for the first time reveals the contribution of miR-26a-2 to LPS tumorigenesis, partly through inhibiting RCBTB1, suggesting that miR-26a-2 is a novel therapeutic target for human LPS.

  17. Physiological, molecular, and cellular mechanisms of impaired seawater tolerance following exposure of Atlantic salmon, Salmo salar, smolts to acid and aluminum

    USGS Publications Warehouse

    Monette, M.Y.; Yada, T.; Matey, V.; McCormick, S.D.

    2010-01-01

    We examined the physiological, molecular, and cellular mechanisms of impaired ion regulation in Atlantic salmon, Salmo salar, smolts following acute acid and aluminum (Al) exposure. Smolts were exposed to: control (pH 6.5, 3.4??gl-1 Al), acid and low Al (LAl: pH 5.4, 11??gl-1 Al), acid and moderate Al (MAl: pH 5.3, 42??gl-1 Al), and acid and high Al (HAl: pH 5.4, 56??gl-1 Al) for two and six days. At each time-point, smolts were sampled directly from freshwater treatment tanks and after a 24h seawater challenge. Exposure to acid/MAl and acid/HAl led to accumulation of gill Al, substantial alterations in gill morphology, reduced gill Na+/K+-ATPase (NKA) activity, and impaired ion regulation in both freshwater and seawater. Exposure to acid/MAl for six days also led to a decrease in gill mRNA expression of the apical Cl- channel (cystic fibrosis transmembrane conductance regulator I), increased apoptosis upon seawater exposure, an increase in the surface expression of mitochondria-rich cells (MRCs) within the filament epithelium of the gill, but reduced abundance of gill NKA-positive MRCs. By contrast, smolts exposed to acid and the lowest Al concentration exhibited minor gill Al accumulation, slight morphological modifications in the gill, and impaired seawater tolerance in the absence of a detectable effect on freshwater ion regulation. These impacts were accompanied by decreased cell proliferation, a slight increase in the surface expression of MRCs within the filament epithelium, but no impact on gill apoptosis or total MRC abundance was observed. However, MRCs in the gills of smolts exposed to acid/LAl exhibited morphological alterations including decreased size, staining intensity, and shape factor. We demonstrate that the seawater tolerance of Atlantic salmon smolts is extremely sensitive to acute exposure to acid and low levels of Al, and that the mechanisms underlying this depend on the time-course and severity of Al exposure. We propose that when smolts are

  18. Self-reported symptoms of chronic cough and breathlessness in working-age men in the city of Izhevsk, Russia: associations with cardiovascular disease risk factors and comorbidities

    PubMed Central

    Cook, Sarah; Quint, Jennifer K; Vasiljev, Maxim; Leon, David A

    2015-01-01

    Introduction Very little is known about the prevalence of respiratory symptoms or their associations with other health conditions in Russia. Methods Between 2008 and 2010, a sample of 983 men resident in Izhevsk, Russia, took part in a cross-sectional survey. Presence of respiratory symptoms was determined from self-report of chronic productive cough and breathlessness assessed using the British Medical Research Council (MRC) breathlessness scale. Self-reported physical and mental health were measured using the 12-Item Short-Form Health Survey (SF-12). Hypertension was assessed from mean blood pressure measured at the health check and/or self-reported use of antihypertensive medication. Other comorbidities were assessed from self-report. Logistic regression models were fitted assessing the association between respiratory symptoms and comorbidities. Linear regression models were fitted to investigate the association between respiratory symptoms and self-reported health scores. All models were adjusted for age, education and smoking status. Results The age-standardised prevalence of cough and breathlessness was 20.9% (prevalence with breathlessness MRC grade 3 or above 3.7%). The majority of men with respiratory symptoms (87.3%) were current smokers. Cough and breathlessness were associated with substantially worse self-reported physical and mental health (test for trend with severity of breathlessness p<0.001). Those with chronic cough and grade 3 or above breathlessness had higher odds of having hypertension (OR 3.03; 95% CI 1.36 to 6.74), diabetes (OR 10.55; 95% CI 2.69 to 41.37), angina pectoris (OR 7.54; 95% CI 3.61 to 15.73), previous myocardial infarction (OR 7.61; 95% CI 2.10 to 27.4) and previous stroke (OR 6.61; 95% CI 1.75 to 23.34) compared with those without respiratory symptoms. Conclusions The prevalence of respiratory symptoms was high. Strong associations were found between respiratory symptoms and cardiovascular comorbidities. These are of

  19. Development and Initial Evaluation of the Web-Based Self-Management Program “Partner in Balance” for Family Caregivers of People With Early Stage Dementia: An Exploratory Mixed-Methods Study

    PubMed Central

    de Vugt, Marjolein E; Withagen, Hanneke EJ; Kempen, Gertrudis IJM; Verhey, Frans RJ

    2016-01-01

    Background People with dementia increasingly depend on informal caregivers. Internet-based self-management interventions hold considerable promise for meeting the educational and support needs of early stage dementia caregivers (EDCs) at a reduced cost. Objective This study aimed to (1) develop an online self-management program for EDC to increase self-efficacy and goal attainment, and (2) evaluate the program’s feasibility and report preliminary data on effectiveness. Methods Based on the Medical Research Council (MRC) framework for the development and evaluation of complex interventions, a stepwise approach was adopted to explore potential user needs and develop and validate the content by means of (1) focus group discussions with dementia caregivers (N=28), (2) interviews with dementia care professionals (N=11), and (3) individual think-aloud usability tests with EDC (N=2) and experts (N=2). A pilot evaluation was conducted with EDC (N=17) to test the feasibility and establish preliminary effects. Self-report measures of feasibility were completed after the completion of intervention. Self-efficacy and goal attainment were evaluated before and after the intervention. Results The different steps provided useful information about the needs of potential users regarding the content and delivery of the program. This resulted in the newly developed “Partner in Balance” program. At the start, system failures resulted in a high noncompleter rate (7/17, 41%), but at the end, an acceptable feasibility score of 209 (range 54-234) was found. The convenience of completing the program at home, the tailored content, and the guidance (face-to-face and online) were appraised positively. Preliminary effects on caregiver self-efficacy (P<.05) and goal attainment (T>50) were promising. Conclusions Adaptations were made to the program to limit the amount of system failures and prevent high noncompleter rates. As recommended by the MRC framework, confirming the feasibility and

  20. Inhibition of NO production by Grindelia argentina and isolation of three new cytotoxic saponins.

    PubMed

    Alza, Natalia P; Pferschy-Wenzig, Eva-Maria; Ortmann, Sabine; Kretschmer, Nadine; Kunert, Olaf; Rechberger, Gerald N; Bauer, Rudolf; Murray, Ana P

    2014-02-01

    A bioassay-guided phytochemical analysis of the ethanolic extract of Grindelia argentina Deble & Oliveira-Deble (Asteraceae) allowed the isolation of a known flavone, hispidulin, and three new oleanane-type saponins, 3-O-β-D-xylopyranosyl-(1→3)-β-D-glucopyranosyl-2β,3β,16α,23-tetrahydroxyolean-12-en-28-oic acid 28-O-β-D-xylopyranosyl-(1→2)-β-D-apiofuranosyl-(1→3)-β-D-xylopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl ester (2), 3-O-β-D-glucopyranosyl-2β,3β,23-trihydroxyolean-12-en-28-oic acid 28-O-β-D-xylopyranosyl-(1→2)-β-D-apiofuranosyl-(1→3)-β-D-xylopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl ester, (3) and 3-O-β-D-xylopyranosyl-(1→3)-β-D-glucopyranosyl-2β,3β,23-trihydroxyolean-12-en-28-oic acid 28-O-β-D-xylopyranosyl-(1→2)-β-D-apiofuranosyl-(1→3)-β-D-xylopyranosyl-(1→3)-α-L-rhamnopyranosyl-(1→2)-α-L-arabinopyranosyl ester (4), named grindeliosides A-C, respectively. Their structures were determined by extensive 1D- and 2D-NMR experiments along with mass spectrometry and chemical evidence. The isolated compounds were evaluated for their inhibitory activities against LPS/IFN-γ-induced NO production in RAW 264.7 macrophages and for their cytotoxic activities against the human leukemic cell line CCRF-CEM and MRC-5 lung fibroblasts. Hispidulin markedly reduced LPS/IFN-γ-induced NO production (IC50 51.4 μM), while grindeliosides A-C were found to be cytotoxic, with grindelioside C being the most active against both CCRF-CEM (IC50 4.2±0.1 μM) and MRC-5 (IC50 4.5±0.1 μM) cell lines.

  1. A study of acute muscle dysfunction with particular reference to dengue myopathy

    PubMed Central

    Verma, Rajesh; Holla, Vikram V.; Kumar, Vijay; Jain, Amita; Husain, Nuzhat; Malhotra, Kiran Preet; Garg, Ravindra Kumar; Malhotra, Hardeep Singh; Sharma, Praveen Kumar; Kumar, Neeraj

    2017-01-01

    Background: Acute myopathy is a common cause of acute motor quadriparesis which has various etiologies with different courses of illness and prognosis depending on the cause. Understanding this diversity helps us in proper approach toward diagnosis, predicting the prognosis, and possible complications and in improving the treatments that are being provided. This study was planned to study the clinical, electrophysiological, and etiological profile of patients presenting with acute myopathy. We also studied how dengue-related acute myopathy differs from other causes and also difference between myopathy due to myositis and hypokalemia in cases of dengue. Materials and Methods: This was a prospective, observational study involving all clinically suspected cases of acute myopathy of not more than 4 weeks duration with raised serum creatine kinase (CK) level. They were subjected to detailed clinical evaluation along with hematological, biochemical, microbiological, and electrophysiological studies and followed-up for outcome at 1 and 3 months. Muscle biopsy and histopathological examination were done in selected patients after taking informed consent. Statistical analysis was performed by appropriate methods using SPSS version 16.0 (Chicago, IL, USA). Results: We evaluated thirty patients of acute myopathy with raised CK level. Seventeen patients had fever, 11 had myalgia, and 5 had skin lesions. All presented with symmetric weakness, 17 (56.7%) patients having predominantly proximal weakness, neck or truncal weakness in 6 (20%), hyporeflexia in 12 (40%), with mean Medical Research Council (MRC) sum score of 46.67 ± 6.0. Eight (mean modified Barthel index [MBI] at presentation - 15 ± 3.7) patients had poor functional status according to MBI and 15 according to modified Rankin scale (MRS) (mean MRS score - 2.5 ± 1.2). Etiology was dengue viral infection in 14 patients; hypokalemia due to various causes other than dengue in 8; pyomyositis in 3; dermatomyositis

  2. A two-decade comparison of prevalence of dementia in individuals aged 65 years and older from three geographical areas of England: results of the Cognitive Function and Ageing Study I and II

    PubMed Central

    Matthews, Fiona E; Arthur, Antony; Barnes, Linda E; Bond, John; Jagger, Carol; Robinson, Louise; Brayne, Carol

    2013-01-01

    Summary Background The prevalence of dementia is of interest worldwide. Contemporary estimates are needed to plan for future care provision, but much evidence is decades old. We aimed to investigate whether the prevalence of dementia had changed in the past two decades by repeating the same approach and diagnostic methods as used in the Medical Research Council Cognitive Function and Ageing Study (MRC CFAS) in three of the original study areas in England. Methods Between 1989 and 1994, MRC CFAS investigators did baseline interviews in populations aged 65 years and older in six geographically defined areas in England and Wales. A two stage process, with screening followed by diagnostic assessment, was used to obtain data for algorithmic diagnoses (geriatric mental state–automated geriatric examination for computer assisted taxonomy), which were then used to estimate dementia prevalence. Data from three of these areas—Cambridgeshire, Newcastle, and Nottingham—were selected for CFAS I. Between 2008 and 2011, new fieldwork was done in the same three areas for the CFAS II study. For both CFAS I and II, each area needed to include 2500 individuals aged 65 years and older to provide power for geographical and generational comparison. Sampling was stratified according to age group (65–74 years vs ≥75 years). CFAS II used identical sampling, approach, and diagnostic methods to CFAS I, except that screening and assessement were combined into one stage. Prevalence estimates were calculated using inverse probability weighting methods to adjust for sampling design and non-response. Full likelihood Bayesian models were used to investigate informative non-response. Findings 7635 people aged 65 years or older were interviewed in CFAS I (9602 approached, 80% response) in Cambridgeshire, Newcastle, and Nottingham, with 1457 being diagnostically assessed. In the same geographical areas, the CFAS II investigators interviewed 7796 individuals (14 242 approached, 242 with

  3. Interactions between hypoxia tolerance and food deprivation in Amazonian oscars, Astronotus ocellatus.

    PubMed

    De Boeck, Gudrun; Wood, Chris M; Iftikar, Fathima I; Matey, Victoria; Scott, Graham R; Sloman, Katherine A; de Nazaré Paula da Silva, Maria; Almeida-Val, Vera M F; Val, Adalberto L

    2013-12-15

    Oscars are often subjected to a combination of low levels of oxygen and fasting during nest-guarding on Amazonian floodplains. We questioned whether this anorexia would aggravate the osmo-respiratory compromise. We compared fed and fasted oscars (10-14 days) in both normoxia and hypoxia (10-20 Torr, 4 h). Routine oxygen consumption rates (O2) were increased by 75% in fasted fish, reflecting behavioural differences, whereas fasting improved hypoxia resistance and critical oxygen tensions (Pcrit) lowered from 54 Torr in fed fish to 34 Torr when fasting. In fed fish, hypoxia reduced liver lipid stores by approximately 50% and total liver energy content by 30%. Fasted fish had a 50% lower hepatosomatic index, resulting in lower total liver protein, glycogen and lipid energy stores under normoxia. Compared with hypoxic fed fish, hypoxic fasted fish only showed reduced liver protein levels and even gained glycogen (+50%) on a per gram basis. This confirms the hypothesis that hypoxia-tolerant fish protect their glycogen stores as much as possible as a safeguard for more prolonged hypoxic events. In general, fasted fish showed lower hydroxyacylCoA dehydrogenase activities compared with fed fish, although this effect was only significant in hypoxic fasted fish. Energy stores and activities of enzymes related to energy metabolism in muscle or gills were not affected. Branchial Na(+) uptake rates were more than two times lower in fed fish, whereas Na(+) efflux was similar. Fed and fasted fish quickly reduced Na(+) uptake and efflux during hypoxia, with fasting fish responding more rapidly. Ammonia excretion and K(+) efflux were reduced under hypoxia, indicating decreased transcellular permeability. Fasted fish had more mitochondria-rich cells (MRC), with larger crypts, indicating the increased importance of the branchial uptake route when feeding is limited. Gill MRC density and surface area were greatly reduced under hypoxia, possibly to reduce ion uptake and efflux rates

  4. Paracrine Mechanisms of Intravenous Bone Marrow-Derived Mononuclear Stem Cells in Chronic Ischemic Stroke

    PubMed Central

    Bhasin, Ashu; Srivastava, M.V. Padma; Mohanty, Sujata; Vivekanandhan, Sivasubramaniam; Sharma, Sakshi; Kumaran, Senthil; Bhatia, Rohit

    2016-01-01

    Background The emerging role of stem cell technology and transplantation has helped scientists to study their potential role in neural repair and regeneration. The fate of stem cells is determined by their niche, consisting of surrounding cells and the secreted trophic growth factors. This interim report evaluates the safety, feasibility and efficacy (if any) of bone marrow-derived mononuclear stem cells (BM-MNC) in chronic ischemic stroke by studying the release of serum vascular endothelial growth factor (VEGF) and brain-derived neurotrophic growth factor (BDNF). Methods Twenty stroke patients and 20 age-matched healthy controls were recruited with the following inclusion criteria: 3 months to 1.5 years from the index event, Medical Research Council (MRC) grade of hand muscles of at least 2, Brunnstrom stage 2-5, conscious, and comprehendible. They were randomized to one group receiving autologous BM-MNC (mean 60-70 million) and to another group receiving saline infusion (placebo). All patients were administered a neuromotor rehabilitation regime for 8 weeks. Clinical assessments [Fugl Meyer scale (FM), modified Barthel index (mBI), MRC grade, Ashworth tone scale] were carried out and serum VEGF and BDNF levels were assessed at baseline and at 8 weeks. Results No serious adverse events were observed during the study. There was no statistically significant clinical improvement between the groups (FM: 95% CI 15.2-5.35, p = 0.25; mBI: 95% CI 14.3-4.5, p = 0.31). VEGF and BDNF expression was found to be greater in group 1 compared to group 2 (VEGF: 442.1 vs. 400.3 pg/ml, p = 0.67; BDNF: 21.3 vs. 19.5 ng/ml) without any statistically significant difference. Conclusion Autologous mononuclear stem cell infusion is safe and tolerable by chronic ischemic stroke patients. The released growth factors (VEGF and BDNF) in the microenvironment could be due to the paracrine hypothesis of stem cell niche and neurorehabilitation regime. PMID:27846623

  5. Symptoms and quality of life in patients with chronic obstructive pulmonary disease treated with aclidinium in a real-life setting

    PubMed Central

    Lange, Peter; Godtfredsen, Nina Skavlan; Olejnicka, Beata; Paradis, Bo-Anders; Curiac, Dan; Humerfelt, Sjur; Telg, Gunilla; Christensen, Helene Nordahl; Bitsch, Magnus Alexander; Andersen, Elisabeth Wreford; Bjermer, Leif

    2016-01-01

    Introduction Chronic obstructive pulmonary disease (COPD) is a progressive disease with symptoms that can have a major impact on patients’ physical health. The aim of this study was to evaluate quality of life (QoL), symptom severity and dyspnoea in COPD patients treated with aclidinium up to 24 weeks. Methods In this prospective non-interventional multicentre study (198 centres in Sweden, Denmark, and Norway), COPD patients (age ≥40 years) who started treatment with aclidinium (initial therapy, change of treatment, or add-on therapy) could be included. Health-related QoL was obtained by COPD assessment test (CAT). Symptoms were evaluated on a 6-point Likert scale. The modified Medical Research Council (mMRC) Dyspnoea Scale was used as a simple grading system to assess the level of dyspnoea/shortness of breath from0 to 4. Patients on treatment with aclidinium who completed baseline and at least one follow-up visit (week 12 or 24) were included in the study population. Results Overall, 1,093 patients were enrolled (mean 69 years, 54% females), one-third had ≥1 exacerbation the year prior to baseline. At enrolment, 48% were LAMA naïve. Mean (standard deviation, SD) CAT score decreased from 16.9 (7.7) at baseline to 14.3 (7.3) at week 24 (p<0.01) with a decrease in all individual CAT items (p<0.05). Mean difference in morning and night-time symptoms from baseline to week 24 was −0.60 (SD 2.51) and −0.44 (SD 2.48), respectively (both p<0.001). Mean (SD) mMRC Dyspnoea Scale changed from 1.6 (1.0) at baseline to 1.5 (1.0) at week 24 (p<0.001). Conclusion In this observational study of a Nordic real-life COPD population, treatment with aclidinium was associated with a clinically important improvement in QoL and morning and night-time symptoms, most pronounced in the LAMA naïve group. However, there is still room for improvement in the management of symptomatic COPD patients. PMID:27387608

  6. CD8+ T lymphocytes in lung tissue from patients with idiopathic pulmonary fibrosis

    PubMed Central

    Daniil, Zoe; Kitsanta, Panagiota; Kapotsis, George; Mathioudaki, Maria; Kollintza, Androniki; Karatza, Marilena; Milic-Emili, Joseph; Roussos, Charis; Papiris, Spyros A

    2005-01-01

    Background Several studies have implicated a role of inflammation in the pathogenesis of lung damage in idiopathic pulmonary fibrosis (IPF). Parenchymal lung damage leads to defects in mechanics and gas exchange and clinically manifests with exertional dyspnea. Investigations of inflammatory cells in IPF have shown that eosinophils, neutrophils and CD8+ TLs may be associated with worse prognosis. We wished to investigate by quantitative immunohistochemistry infiltrating macrophages, neutrophils and T lymphocytes (TLs) subpopulations (CD3+, CD4+ and CD8+) in lung tissue of patients with IPF and their correlation with lung function indices and grade of dyspnoea. Methods Surgical biopsies of 12 patients with IPF were immunohistochemically stained with mouse monoclonal antibodies (anti-CD68 for macrophages, anti-elastase for neutrophils, and anti-CD3, anti-CD4, anti-CD8 for CD3+TLs, CD4+TLs, and CD8+TLs respectively). The number of positively stained cells was determined by observer-interactive computerized image analysis (SAMBA microscopic image processor). Cell numbers were expressed in percentage of immunopositive nuclear surface in relation to the total nuclear surface of infiltrative cells within the tissue (labeling Index). Correlations were performed between cell numbers and physiological indices [FEV1, FVC, TLC, DLCO, PaO2, PaCO2 and P(A-a)O2)] as well as dyspnoea scores assessed by the Medical Research Council (MRC) scale. Results Elastase positive cells accounted for the 7.04% ± 1.1 of total cells, CD68+ cells for the 16.6% ± 2, CD3+ TLs for the 28.8% ± 7, CD4+ TLs for the 14.5 ± 4 and CD8+ TLs for the 13.8 ± 4. CD8+TLs correlated inversely with FVC % predicted (rs = -0.67, p = 0.01), TLC % predicted (rs = -0.68, p = 0.01), DLCO % predicted (rs = -0.61, p = 0.04), and PaO2 (rs = -0.60, p = 0.04). Positive correlations were found between CD8+TLs and P(A-a)O2 (rs = 0.65, p = 0.02) and CD8+TLs and MRC score (rs = 0.63, p = 0.02). Additionally, CD68+ cells

  7. Factor analysis of laboratory and clinical measurements of dyspnea in patients with chronic obstructive pulmonary disease.

    PubMed

    Nguyen, Huong Q; Altinger, Julie; Carrieri-Kohlman, Virginia; Gormley, Jenny M; Stulbarg, Michael S

    2003-02-01

    The primary purpose of this study was to determine if there are three distinct factors representing ratings of dyspnea during laboratory exercise, clinical ratings of dyspnea, and pulmonary function in patients with moderate to severe chronic obstructive pulmonary disease (COPD) (n = 92) using factor analysis. Subjects (mean age 66 +/- 7 yrs; FEV1% predicted 44.7 +/- 14.0) were randomly assigned to one of three treatment groups to test the effects of three education and exercise training programs. Outcomes were evaluated at baseline and at 2 months after the intervention. Dyspnea ratings with laboratory exercise (SOB) were measured during incremental (ITT) and endurance (ETT) treadmill tests, and a six-minute walk (6MW) using the modified Borg scale. Clinical measures of dyspnea were measured with the Baseline and Transitional Dyspnea Index (BDI/TDI), UCSD Shortness of Breath Questionnaire (SOBQ), Medical Research Council Dyspnea Scale (MRC), Dyspnea subscale of the Chronic Respiratory Questionnaire (CRQ-D), and a global dyspnea question. Pulmonary function parameters included FEV1% predicted, FEV1/FVC, and RV/TLC. The factor analysis yielded three factors that accounted for 58.7% of the total variance in the data: Factor 1, "Dyspnea with Laboratory Exercise" comprised ETT SOB end, ETT SOB isotime, ITTSOB end, ITT SOB isotime, ITT SOB/Time and ETT SOB/Time. Factor 2, "Clinical Dyspnea," comprised 6MW SOB, 6MW SOB/Feet, BDI, SOBQ, MRC, Global SOB, CRQ-D. Measures of airway resistance (FEV1% predicted, FEV1/FVC) and hyperinflation (RV/TLC) loaded on a third factor, "Pulmonary Function." An additional post hoc factor analysis with post-intervention data provided similar results. The Global SOB question and ITT SOB isostage variables were relatively more sensitive to change compared to the other outcome variables. We conclude that pulmonary function, clinical ratings of dyspnea, and laboratory ratings of dyspnea are three separate and independent factors and should be

  8. Continuing to Confront COPD International Patient Survey: methods, COPD prevalence, and disease burden in 2012–2013

    PubMed Central

    Landis, Sarah H; Muellerova, Hana; Mannino, David M; Menezes, Ana M; Han, MeiLan K; van der Molen, Thys; Ichinose, Masakazu; Aisanov, Zaurbek; Oh, Yeon-Mok; Davis, Kourtney J

    2014-01-01

    Purpose The Continuing to Confront COPD International Patient Survey aimed to estimate the prevalence and burden of COPD globally and to update findings from the Confronting COPD International Survey conducted in 1999–2000. Materials and methods Chronic obstructive pulmonary disease (COPD) patients in 12 countries worldwide were identified through systematic screening of population samples. Telephone and face-to-face interviews were conducted between November 2012 and May 2013 using a structured survey that incorporated validated patient-reported outcome instruments. Eligible patients were adults aged 40 years and older who were taking regular respiratory medications or suffered with chronic respiratory symptoms and reported either 1) a physician diagnosis of COPD/emphysema, 2) a physician diagnosis of chronic bronchitis, or 3) a symptom-based definition of chronic bronchitis. The burden of COPD was measured with the COPD Assessment Test (CAT) and the modified Medical Research Council (mMRC) Dyspnea Scale. Results Of 106,876 households with at least one person aged ≥40 years, 4,343 respondents fulfilled the case definition of COPD and completed the full survey. COPD prevalence ranged from 7% to 12%, with most countries falling within the range of 7%–9%. In all countries, prevalence increased with age, and in all countries except the US was greater among men (range 6%–14%) than among women (range 5%–11%). A significant disease burden was observed when considering COPD symptoms or health status, and showed wide variations across countries. Prevalence of moderate-to-severe dyspnea (mMRC scale ≥2) ranged from 27% to 61%, and mean CAT score ranged from 16.0 to 24.8, indicating medium-to-high impairment. Conclusion This survey, representing 12 countries, showed similar rates of estimated COPD prevalence across countries that were higher than those reported a decade ago in the original Confronting COPD International Survey. A significant burden of COPD was

  9. First human experience with autologous Schwann cells to supplement sciatic nerve repair: report of 2 cases with long-term follow-up.

    PubMed

    Gersey, Zachary C; Burks, S Shelby; Anderson, Kim D; Dididze, Marine; Khan, Aisha; Dietrich, W Dalton; Levi, Allan D

    2017-03-01

    OBJECTIVE Long-segment injuries to large peripheral nerves present a challenge to surgeons because insufficient donor tissue limits repair. Multiple supplemental approaches have been investigated, including the use of Schwann cells (SCs). The authors present the first 2 cases using autologous SCs to supplement a peripheral nerve graft repair in humans with long-term follow-up data. METHODS Two patients were enrolled in an FDA-approved trial to assess the safety of using expanded populations of autologous SCs to supplement the repair of long-segment injuries to the sciatic nerve. The mechanism of injury included a boat propeller and a gunshot wound. The SCs were obtained from both the sural nerve and damaged sciatic nerve stump. The SCs were expanded and purified in culture by using heregulin β1 and forskolin. Repair was performed with sural nerve grafts, SCs in suspension, and a Duragen graft to house the construct. Follow-up was 36 and 12 months for the patients in Cases 1 and 2, respectively. RESULTS The patient in Case 1 had a boat propeller injury with complete transection of both sciatic divisions at midthigh. The graft length was approximately 7.5 cm. In the postoperative period the patient regained motor function (Medical Research Council [MRC] Grade 5/5) in the tibial distribution, with partial function in peroneal distribution (MRC Grade 2/5 on dorsiflexion). Partial return of sensory function was also achieved, and neuropathic pain was completely resolved. The patient in Case 2 sustained a gunshot wound to the leg, with partial disruption of the tibial division of the sciatic nerve at the midthigh. The graft length was 5 cm. Postoperatively the patient regained complete motor function of the tibial nerve, with partial return of sensation. Long-term follow-up with both MRI and ultrasound demonstrated nerve graft continuity and the absence of tumor formation at the repair site. CONCLUSIONS Presented here are the first 2 cases in which autologous SCs were

  10. Correlation of chest computed tomography findings with dyspnea and lung functions in post-tubercular sequelae

    PubMed Central

    Panda, Ananya; Bhalla, Ashu Seith; Sharma, Raju; Mohan, Anant; Sreenivas, Vishnu; Kalaimannan, Umasankar; Upadhyay, Ashish Dutt

    2016-01-01

    Aims: To study the correlation between dyspnea, radiological findings, and pulmonary function tests (PFTs) in patients with sequelae of pulmonary tuberculosis (TB). Materials and Methods: Clinical history, chest computed tomography (CT), and PFT of patients with post-TB sequelae were recorded. Dyspnea was graded according to the Modified Medical Research Council (mMRC) scale. CT scans were analyzed for fibrosis, cavitation, bronchiectasis, consolidation, nodules, and aspergilloma. Semi-quantitative analysis was done for these abnormalities. Scores were added to obtain a total morphological score (TMS). The lungs were also divided into three zones and scores added to obtain the total lung score (TLS). Spirometry was done for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), and FEV1/FVC. Results: Dyspnea was present in 58/101 patients. A total of 22/58 patients had mMRC Grade 1, and 17/58 patients had Grades 2 and 3 dyspnea each. There was a significant difference in median fibrosis, bronchiectasis, nodules (P < 0.01) scores, TMS, and TLS (P < 0.0001) between dyspnea and nondyspnea groups. Significant correlations were obtained between grades of dyspnea and fibrosis (r = 0.34, P = 0.006), bronchiectasis (r = 0.35, P = 0.004), nodule (r = 0.24, P = 0.016) scores, TMS (r = 0.398, P = 0.000), and TLS (r = 0.35, P = 0.0003). PFTs were impaired in 78/101 (77.2%) patients. Restrictive defect was most common in 39.6% followed by mixed in 34.7%. There was a negative but statistically insignificant trend between PFT and fibrosis, bronchiectasis, nodule scores, TMS, and TLS. However, there were significant differences in median fibrosis, cavitation, and bronchiectasis scores in patients with normal, mild to moderate, and severe respiratory defects. No difference was seen in TMS and TLS according to the severity of the respiratory defect. Conclusion: Both fibrosis and bronchiectasis correlated with dyspnea an