WorldWideScience

Sample records for m1 pre-sma pmc

  1. Domain general sequence operations contribute to pre-SMA involvement in visuo-spatial processing

    Directory of Open Access Journals (Sweden)

    E. Charles eLeek

    2016-01-01

    Full Text Available This study used 3T MRI to elucidate the functional role of supplementary motor area (SMA in relation to visuo-spatial processing. A localizer task contrasting sequential number subtraction and repetitive button pressing was used to functionally delineate non-motor sequence processing in pre-SMA, and activity in SMA-proper associated with motor sequencing. Patterns of BOLD responses in these regions were then contrasted to those from two tasks of visuo-spatial processing. In one task participants performed mental rotation in which recognition memory judgments were made to previously memorized 2D novel patterns across image-plane rotations. The other task involved abstract grid navigation in which observers computed a series of imagined location shifts in response to directional (arrow cues around a mental grid. The results showed overlapping activation in pre-SMA for sequential subtraction and both visuo-spatial tasks. These results suggest that visuo-spatial processing is supported by non-motor sequence operations that involve pre-SMA. More broadly, these data further highlight the functional heterogeneity of pre-SMA, and show that its role extends to processes beyond the planning and online control of movement.

  2. Semantic memory retrieval circuit: role of pre-SMA, caudate, and thalamus.

    Science.gov (United States)

    Hart, John; Maguire, Mandy J; Motes, Michael; Mudar, Raksha Anand; Chiang, Hsueh-Sheng; Womack, Kyle B; Kraut, Michael A

    2013-07-01

    We propose that pre-supplementary motor area (pre-SMA)-thalamic interactions govern processes fundamental to semantic retrieval of an integrated object memory. At the onset of semantic retrieval, pre-SMA initiates electrical interactions between multiple cortical regions associated with semantic memory subsystems encodings as indexed by an increase in theta-band EEG power. This starts between 100-150 ms after stimulus presentation and is sustained throughout the task. We posit that this activity represents initiation of the object memory search, which continues in searching for an object memory. When the correct memory is retrieved, there is a high beta-band EEG power increase, which reflects communication between pre-SMA and thalamus, designates the end of the search process and resultant in object retrieval from multiple semantic memory subsystems. This high beta signal is also detected in cortical regions. This circuit is modulated by the caudate nuclei to facilitate correct and suppress incorrect target memories. Copyright © 2012 Elsevier Inc. All rights reserved.

  3. Sense of agency is related to gamma band coupling in an inferior parietal-preSMA circuitry

    DEFF Research Database (Denmark)

    Ritterband-Rosenbaum, Anina; Nielsen, Jens Bo; Christensen, Mark Schram

    2014-01-01

    with no SoA in the late task phase, but the test of the early task phase did not reveal any differences between presence and absence of SoA. We show that SoA is associated with a directionally specific between frequencies coupling from IPC to preSMA in the higher gamma (ɣ) band in the late task phase...

  4. Sense of agency is related to gamma band coupling in an inferior parietal-preSMA circuitry

    Directory of Open Access Journals (Sweden)

    Anina eRitterband-Rosenbaum

    2014-07-01

    Full Text Available In the present study we tested whether sense of agency (SoA is reflected by changes in coupling between right medio-frontal/supplementary motor area (SMA and inferior parietal cortex (IPC. Twelve healthy adult volunteers participated in the study. They performed a variation of a line-drawing task (Nielsen, 1963;Fourneret and Jeannerod, 1998, in which they moved a cursor on a digital tablet with their right hand without seeing the hand. Visual feedback displayed on a computer monitor was either in correspondence with or deviated from the actual movement. This made participants uncertain as to the agent of the movement and they reported SoA in approximately 50% of trials when the movement was computer-generated. We tested whether IPC-preSMA coupling was associated with SoA, using dynamic causal modelling (DCM for induced responses (Chen et al., 2008;Herz et al., 2012. Nine different DCMs were constructed for the early and late phases of the task, respectively. All models included two regions: a superior medial gyrus (preSMA region and a right supramarginal gyrus (IPC region. Bayesian models selection (Stephan et al., 2009 favoured a model with input to IPC and modulation of the forward connection to SMA in the late task phase, and a model with input to preSMA and modulation of the backward connection was favoured for the early task phase. The analysis shows that IPC source activity in the 50-60Hz range modulated preSMA source activity in the 40-70 Hz range in the presence of SoA compared with no SoA in the late task phase, but the test of the early task phase did not reveal any differences between presence and absence of SoA. We show that SoA is associated with a directionally specific between frequencies coupling from IPC to preSMA in the higher gamma (ɣ band in the late task phase. This suggests that SoA is a retrospective perception, which is highly dependent on interpretation of the outcome of the performed action.

  5. Sense of agency is related to gamma band coupling in an inferior parietal-preSMA circuitry

    Science.gov (United States)

    Ritterband-Rosenbaum, Anina; Nielsen, Jens B.; Christensen, Mark S.

    2014-01-01

    In the present study we tested whether sense of agency (SoA) is reflected by changes in coupling between right medio-frontal/supplementary motor area (SMA) and inferior parietal cortex (IPC). Twelve healthy adult volunteers participated in the study. They performed a variation of a line-drawing task (Nielsen, 1963; Fourneret and Jeannerod, 1998), in which they moved a cursor on a digital tablet with their right hand without seeing the hand. Visual feedback displayed on a computer monitor was either in correspondence with or deviated from the actual movement. This made participants uncertain as to the agent of the movement and they reported SoA in approximately 50% of trials when the movement was computer-generated. We tested whether IPC-preSMA coupling was associated with SoA, using dynamic causal modeling (DCM) for induced responses (Chen et al., 2008; Herz et al., 2012). Nine different DCMs were constructed for the early and late phases of the task, respectively. All models included two regions: a superior medial gyrus (preSMA) region and a right supramarginal gyrus (IPC) region. Bayesian models selection (Stephan et al., 2009) favored a model with input to IPC and modulation of the forward connection to SMA in the late task phase, and a model with input to preSMA and modulation of the backward connection was favored for the early task phase. The analysis shows that IPC source activity in the 50–60 Hz range modulated preSMA source activity in the 40–70 Hz range in the presence of SoA compared with no SoA in the late task phase, but the test of the early task phase did not reveal any differences between presence and absence of SoA. We show that SoA is associated with a directionally specific between frequencies coupling from IPC to preSMA in the higher gamma (ɣ) band in the late task phase. This suggests that SoA is a retrospective perception, which is highly dependent on interpretation of the outcome of the performed action. PMID:25076883

  6. Contribution of the pre-SMA to the production of words and non-speech oral motor gestures, as revealed by repetitive transcranial magnetic stimulation (rTMS).

    Science.gov (United States)

    Tremblay, Pascale; Gracco, Vincent L

    2009-05-01

    An emerging theoretical perspective, largely based on neuroimaging studies, suggests that the pre-SMA is involved in planning cognitive aspects of motor behavior and language, such as linguistic and non-linguistic response selection. Neuroimaging studies, however, cannot indicate whether a brain region is equally important to all tasks in which it is activated. In the present study, we tested the hypothesis that the pre-SMA is an important component of response selection, using an interference technique. High frequency repetitive TMS (10 Hz) was used to interfere with the functioning of the pre-SMA during tasks requiring selection of words and oral gestures under different selection modes (forced, volitional) and attention levels (high attention, low attention). Results show that TMS applied to the pre-SMA interferes selectively with the volitional selection condition, resulting in longer RTs. The low- and high-attention forced selection conditions were unaffected by TMS, demonstrating that the pre-SMA is sensitive to selection mode but not attentional demands. TMS similarly affected the volitional selection of words and oral gestures, reflecting the response-independent nature of the pre-SMA contribution to response selection. The implications of these results are discussed.

  7. PreSMA stimulation changes task-free functional connectivity in the fronto-basal-ganglia that correlates with response inhibition efficiency.

    Science.gov (United States)

    Xu, Benjamin; Sandrini, Marco; Wang, Wen-Tung; Smith, Jason F; Sarlls, Joelle E; Awosika, Oluwole; Butman, John A; Horwitz, Barry; Cohen, Leonardo G

    2016-09-01

    Previous work using transcranial magnetic stimulation (TMS) demonstrated that the right presupplementary motor area (preSMA), a node in the fronto-basal-ganglia network, is critical for response inhibition. However, TMS influences interconnected regions, raising the possibility of a link between the preSMA activity and the functional connectivity within the network. To understand this relationship, we applied single-pulse TMS to the right preSMA during functional magnetic resonance imaging when the subjects were at rest to examine changes in neural activity and functional connectivity within the network in relation to the efficiency of response inhibition evaluated with a stop-signal task. The results showed that preSMA-TMS increased activation in the right inferior-frontal cortex (rIFC) and basal ganglia and modulated their task-free functional connectivity. Both the TMS-induced changes in the basal-ganglia activation and the functional connectivity between rIFC and left striatum, and of the overall network correlated with the efficiency of response inhibition and with the white-matter microstructure along the preSMA-rIFC pathway. These results suggest that the task-free functional and structural connectivity between the rIFCop and basal ganglia are critical to the efficiency of response inhibition. Hum Brain Mapp 37:3236-3249, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. Pre-SMA gray-matter density predicts individual differences in action selection in the face of conscious and unconscious response conflict

    NARCIS (Netherlands)

    van Gaal, S.; Scholte, H.S.; Lamme, V.A.F.; Fahrenfort, J.J.; Ridderinkhof, K.R.

    2011-01-01

    The presupplementary motor area (pre-SMA) is considered key in contributing to voluntary action selection during response conflict. Here we test whether individual differences in the ability to select appropriate actions in the face of strong (conscious) and weak (virtually unconscious) distracting

  9. 77 FR 55895 - Meeting: RTCA Program Management Committee (PMC)

    Science.gov (United States)

    2012-09-11

    ... DEPARTMENT OF TRANSPORTATION Federal Aviation Administration Meeting: RTCA Program Management Committee (PMC) AGENCY: Federal Aviation Administration (FAA), U.S. Department of Transportation (DOT...--Concept of Use for Aeronautical Information Services (AIS) and Meteorological (MET) Data Link Services...

  10. Europe PMC: a full-text literature database for the life sciences and platform for innovation

    Science.gov (United States)

    2015-01-01

    This article describes recent developments of Europe PMC (http://europepmc.org), the leading database for life science literature. Formerly known as UKPMC, the service was rebranded in November 2012 as Europe PMC to reflect the scope of the funding agencies that support it. Several new developments have enriched Europe PMC considerably since then. Europe PMC now offers RESTful web services to access both articles and grants, powerful search tools such as citation-count sort order and data citation features, a service to add publications to your ORCID, a variety of export formats, and an External Links service that enables any related resource to be linked from Europe PMC content. PMID:25378340

  11. Ultrasound spectroscopy: application on MMC and PMC materials

    Energy Technology Data Exchange (ETDEWEB)

    Schwarz, Ricardo B [Los Alamos National Laboratory; Vuorinen, Jyki [TAMPERE UNIV TECHNOLOGY; Kuokkala, Veli - Tapani [TAMPERE UNIV TECHNOLOGY

    2010-01-01

    Resonant Ultrasound Spectroscopy (RUS) is a simple technique for measuring the second-order elastic constants and ultrasonic attenuation of solids. The technique is based on measuring the spectrum of mechanical resonances for a sample of known shape (usually a sphere, cylinder, or parallelepiped). This spectrum cannot be deconvoluted to deduce the elastic constants. Instead, an approximate spectrum is calculated from the known sample dimensions, its mass, and a set of 'guessed' elastic constants. A multidimensional minimization of the rms difference between the measured and calculated spectra enables us to deduce all the elastic constants of the solid from a single frequency scan. Currently, the technique can be applied to crystals of orthorhombic symmetry (9 elastic constants) or higher using desktop computers and software developed for this purpose. Composite materials, especially fiber composites, can take full advantage of the RUS technique as they typically have low symmetry. In this paper we summarize the RUS technique and provide examples of its application to the elastic characterization of both fiber reinforced MMC's, and fiber reinforced PMC's.

  12. PMC-12, a traditional herbal medicine, enhances learning memory and hippocampal neurogenesis in mice.

    Science.gov (United States)

    Park, Hee Ra; Kim, Ju Yeon; Lee, Yujeong; Chun, Hye Jeong; Choi, Young Whan; Shin, Hwa Kyoung; Choi, Byung Tae; Kim, Cheol Min; Lee, Jaewon

    2016-03-23

    The beneficial effects of traditional Korean medicine are recognized during the treatment of neurodegenerative conditions, such as, Alzheimer's disease and neurocognitive dysfunction, and recently, hippocampal neurogenesis has been reported to be associated with memory function. In this study, the authors investigated the beneficial effects of polygonum multiflorum Thunberg complex composition-12 (PMC-12), which is a mixture of four medicinal herbs, that is, Polygonum multiflorum, Polygala tenuifolia, Rehmannia glutinosa, and Acorus gramineus, on hippocampal neurogenesis, learning, and memory in mice. PMC-12 was orally administered to male C57BL/6 mice (5 weeks old) at 100 or 500 mg/kg daily for 2 weeks. PMC-12 administration significantly was found to increase the proliferation of neural progenitor cells and the survival of newly-generated cells in the dentate gyrus. In the Morris water maze test, the latency times of PMC-12 treated mice (100 or 500 mg/kg) were shorter than those of vehicle-control mice. In addition, PMC-12 increased the levels of BDNF, p-CREB, and synaptophysin, which are known to be associated with neural plasticity and hippocampal neurogenesis. These findings suggest PMC-12 enhances hippocampal neurogenesis and neurocognitive function and imply that PMC-12 ameliorates memory impairment and cognitive deficits. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  13. Cathodal transcranial direct current stimulation (tDCS) applied to the left premotor cortex (PMC) stabilizes a newly learned motor sequence.

    Science.gov (United States)

    Focke, Jan; Kemmet, Sylvia; Krause, Vanessa; Keitel, Ariane; Pollok, Bettina

    2017-01-01

    While the primary motor cortex (M1) is involved in the acquisition the premotor cortex (PMC) has been related to over-night consolidation of a newly learned motor skill. The present study aims at investigating the possible contribution of the left PMC for the stabilization of a motor sequence immediately after acquisition as determined by susceptibility to interference. Thirty six healthy volunteers received anodal, cathodal and sham transcranial direct current stimulation (tDCS) to the left PMC either immediately prior to or during training on a serial reaction time task (SRTT) with the right hand. TDCS was applied for 10min, respectively. Reaction times were measured prior to training (t1), at the end of training (t2), and after presentation of an interfering random pattern (t3). Beyond interference from learning, the random pattern served as control condition in order to estimate general effects of tDCS on reaction times. TDCS applied during SRTT training did not result in any significant effects neither on acquisition nor on susceptibility to interference. In contrast to this, tDCS prior to SRTT training yielded an unspecific facilitation of reaction times at t2 independent of tDCS polarity. At t3, reduced susceptibility to interference was found following cathodal stimulation. The results suggest the involvement of the PMC in early consolidation and reveal a piece of evidence for the hypothesis that behavioral tDCS effects vary with the activation state of the stimulated area. Copyright © 2016. Published by Elsevier B.V.

  14. PMC-12, a Prescription of Traditional Korean Medicine, Improves Amyloid β-Induced Cognitive Deficits through Modulation of Neuroinflammation

    Directory of Open Access Journals (Sweden)

    Min Young Park

    2015-01-01

    Full Text Available PMC-12 is a prescription used in traditional Korean medicine that consists of a mixture of four herbal medicines, Polygonum multiflorum, Rehmannia glutinosa, Polygala tenuifolia, and Acorus gramineus, which have been reported to have various pharmacological effects on age-related neurological diseases. In the present study, we investigated whether PMC-12 improves cognitive deficits associated with decreased neuroinflammation in an amyloid-β-(Aβ- induced mouse model and exerts the antineuroinflammatory effects in lipopolysaccharide-(LPS- stimulated murine BV2 microglia. Intracerebroventricular injection of Aβ25-35 in mice resulted in impairment in learning and spatial memory, whereas this was reversed by oral administration of PMC-12 (100 and 500 mg/kg/day in dose-dependent manners. Moreover, PMC-12 reduced the increase of Aβ expression and activation of microglia and astrocytes in the Aβ25-35-injected brain. Furthermore, quantitative PCR data showed that inflammatory mediators were significantly decreased by administration of PMC-12 in Aβ-injected brains. Consistent with the in vivo data, PMC-12 significantly reduced the inflammatory mediators in LPS-stimulated BV2 cells without cell toxicity. Moreover, PMC-12 exhibited anti-inflammatory properties via downregulation of ERK, JNK, and p38 MAPK pathways. These findings suggest that the protective effects of PMC-12 may be mediated by its antineuroinflammatory activities, resulting in the attenuation of memory impairment; accordingly, PMC-12 may be useful in the prevention and treatment of AD.

  15. Downregulation of hPMC2 imparts chemotherapeutic sensitivity to alkylating agents in breast cancer cells.

    Science.gov (United States)

    Krishnamurthy, Nirmala; Liu, Lili; Xiong, Xiahui; Zhang, Junran; Montano, Monica M

    2015-01-01

    Triple negative breast cancer cell lines have been reported to be resistant to the cyotoxic effects of temozolomide (TMZ). We have shown previously that a novel protein, human homolog of Xenopus gene which Prevents Mitotic Catastrophe (hPMC2) has a role in the repair of estrogen-induced abasic sites. Our present study provides evidence that downregulation of hPMC2 in MDA-MB-231 and MDA-MB-468 breast cancer cells treated with temozolomide (TMZ) decreases cell survival. This increased sensitivity to TMZ is associated with an increase in number of apurinic/apyrimidinic (AP) sites in the DNA. We also show that treatment with another alkylating agent, BCNU, results in an increase in AP sites and decrease in cell survival. Quantification of western blot analyses and immunofluorescence experiments reveal that treatment of hPMC2 downregulated cells with TMZ results in an increase in γ-H2AX levels, suggesting an increase in double strand DNA breaks. The enhancement of DNA double strand breaks in TMZ treated cells upon downregulation of hPCM2 is also revealed by the comet assay. Overall, we provide evidence that downregulation of hPMC2 in breast cancer cells increases cytotoxicity of alkylating agents, representing a novel mechanism of treatment for breast cancer. Our data thus has important clinical implications in the management of breast cancer and brings forth potentially new therapeutic strategies.

  16. Project Management Consultancy (PMC) procurement approach: Supplier's evaluation and selection dilemma

    Science.gov (United States)

    Nawi, Mohd Nasrun Mohd; Azimi, Mohd Azrulfitri; Pozin, Mohd Affendi Ahmad; Osman, Wan Nadri; Anuar, Herman Shah

    2016-08-01

    Project Management Consultancy (PMC) is part of the management oriented procurement method in which a sole consultant is hired by the client to deal with the contactors in place of the client. Appointing contractors in this method or approach looks to be interesting as client could play a pivotal role in evaluating and selecting the supplier/contractor for the work package. In some cases, client gives the authority for the PMC to hire the supplier/contractor of their choice while in some cases the client is the one who made the decision. This research paper seeks to investigate the dilemma arises from this situation and for the purpose of this research, a real case study was studied to assess the impacts of such dilemma to the performance of the project. Recommendations on how to tackle the dilemma will also be addressed in the later part of this research paper.

  17. Revised Correlation between Odin/OSIRIS PMC Properties and Coincident TIMED/SABER Mesospheric Temperatures

    Science.gov (United States)

    Feofilov, A. G.; Petelina, S. V.; Kutepov, A. A.; Pesnell, W. D.; Goldberg, R. A.; Llewellyn, E. J.; Russell, J. M.

    2006-01-01

    The Optical Spectrograph and Infrared Imaging System (OSIRIS) instrument on board the Odin satellite detects Polar Mesospheric Clouds (PMCs) through the enhancement in the limb-scattered solar radiance. The Sounding of the Atmosphere using the Broadband Emission Radiometry (SABER) instrument on board the TIMED satellite is a limb scanning infrared radiometer that measures temperature and vertical profiles and energetic parameters for minor constituents in the mesosphere and lower thermosphere. The combination of OSIRIS and SABER data has been previously used to statistically derive thermal conditions for PMC existence [Petelina et al., 2005]. a, A.A. Kutepov, W.D. Pesnell, In this work, we employ the simultaneous common volume measurements of PMCs by OSIRIS and temperature profiles measured by SABER for the Northern Hemisphere summers of 2002-2005 and corrected in the polar region by accounting for the vibrational-vibrational energy exchange among the CO2 isotopes [Kutepov et al., 2006]. For each of 20 coincidences identified within plus or minus 1 degree latitude, plus or minus 2 degrees longitude and less than 1 hour time the frost point temperatures were calculated using the corresponding SABER temperature profile and water vapor densities of 1,3, and 10 ppmv. We found that the PMC presence and brightness correlated only with the temperature threshold that corresponds to the frost point. The absolute value of the temperature below the frost point, however, didn't play a significant role in the intensity of PMC signal for the majority of selected coincidences. The presence of several bright clouds at temperatures above the frost point is obviously related to the limitation of the limb geometry when some near- or far-field PMCs located at higher (and warmer) altitudes appear to be at lower altitudes.

  18. Making limb and nadir measurements comparable: A common volume study of PMC brightness observed by Odin OSIRIS and AIM CIPS

    Science.gov (United States)

    Benze, Susanne; Gumbel, Jörg; Randall, Cora E.; Karlsson, Bodil; Hultgren, Kristoffer; Lumpe, Jerry D.; Baumgarten, Gerd

    2018-01-01

    Combining limb and nadir satellite observations of Polar Mesospheric Clouds (PMCs) has long been recognized as problematic due to differences in observation geometry, scattering conditions, and retrieval approaches. This study offers a method of comparing PMC brightness observations from the nadir-viewing Aeronomy of Ice in the Mesosphere (AIM) Cloud Imaging and Particle Size (CIPS) instrument and the limb-viewing Odin Optical Spectrograph and InfraRed Imaging System (OSIRIS). OSIRIS and CIPS measurements are made comparable by defining a common volume for overlapping OSIRIS and CIPS observations for two northern hemisphere (NH) PMC seasons: NH08 and NH09. We define a scattering intensity quantity that is suitable for either nadir or limb observations and for different scattering conditions. A known CIPS bias is applied, differences in instrument sensitivity are analyzed and taken into account, and effects of cloud inhomogeneity and common volume definition on the comparison are discussed. Not accounting for instrument sensitivity differences or inhomogeneities in the PMC field, the mean relative difference in cloud brightness (CIPS - OSIRIS) is -102 ± 55%. The differences are largest for coincidences with very inhomogeneous clouds that are dominated by pixels that CIPS reports as non-cloud points. Removing these coincidences, the mean relative difference in cloud brightness reduces to -6 ± 14%. The correlation coefficient between the CIPS and OSIRIS measurements of PMC brightness variations in space and time is remarkably high, at 0.94. Overall, the comparison shows excellent agreement despite different retrieval approaches and observation geometries.

  19. Spatiotemporal analysis of tropical disease research combining Europe PMC and affiliation mapping web services.

    Science.gov (United States)

    Palmblad, Magnus; Torvik, Vetle I

    2017-01-01

    Tropical medicine appeared as a distinct sub-discipline in the late nineteenth century, during a period of rapid European colonial expansion in Africa and Asia. After a dramatic drop after World War II, research on tropical diseases have received more attention and research funding in the twenty-first century. We used Apache Taverna to integrate Europe PMC and MapAffil web services, containing the spatiotemporal analysis workflow from a list of PubMed queries to a list of publication years and author affiliations geoparsed to latitudes and longitudes. The results could then be visualized in the Quantum Geographic Information System (QGIS). Our workflows automatically matched 253,277 affiliations to geographical coordinates for the first authors of 379,728 papers on tropical diseases in a single execution. The bibliometric analyses show how research output in tropical diseases follow major historical shifts in the twentieth century and renewed interest in and funding for tropical disease research in the twenty-first century. They show the effects of disease outbreaks, WHO eradication programs, vaccine developments, wars, refugee migrations, and peace treaties. Literature search and geoparsing web services can be combined in scientific workflows performing a complete spatiotemporal bibliometric analyses of research in tropical medicine. The workflows and datasets are freely available and can be used to reproduce or refine the analyses and test specific hypotheses or look into particular diseases or geographic regions. This work exceeds all previously published bibliometric analyses on tropical diseases in both scale and spatiotemporal range.

  20. m=1” coatings

    DEFF Research Database (Denmark)

    Cooper-Jensen, C.; Klinkby, Esben Bryndt; Beaucour, J.

    For neutrons the critical angle of Ni is defined as m=1. If one needs a coating with reflectivity above m=1, people have traditionally used Ni58 or Ni-based multilayers. The reason to use Ni is the high neutron scattering density and the fact that it is easy to coat Ni using magnetron sputtering....... For a neutron guide the cost of shielding around the guide is a substantial part of the total cost of the guide. We are therefore looking at other materials than Ni for m=1 coatings. Both Be and diamond have the same or higher neutron scattering density than Ni, and have a much smaller absorption cross section....... Because of the lower absorption cross section, and because of fewer emitted gamma ray photons when a neutron is absorbed, these coatings are producing much less gamma radiation and therefore reduce the shielding costs. Be is frequently used in a wide range of science and technology applications. The only...

  1. Predicting Trainability of M1 Crewmen

    Science.gov (United States)

    1982-10-01

    Load Main Gun Clear Main Gun LOAD/UNLOAD M250 GRENADE LAUNCHER ON M1 TANK* Load Grenade Launcher Unload Grenade Launcher PREPARE GUNNER’S STATION...Clear Main Gun LOAD/UNLOAD M250 GRENADE LAUNCHER ON Ml TANK* Load Grenade Launcher Unload Grenade Lauacher PREPARE GUNNER’S STATION FOR OPERATION ON Ml

  2. Effects of admittance and gyrotropy on the scattering due to chiro-ferrite medium coated microstructured PMC cylinder

    Science.gov (United States)

    Iqbal, N.; Choudhury, P. K.

    2017-12-01

    The paper deals with scattering of electromagnetic (EM) waves by perfectly magnetic conducting (PMC) cylinder coated with chiro-ferrite medium under the assumption of oblique angle of incidence wave with perpendicular polarization (transverse electric; TE). An on-demand (in respect of orientation) kind of conducting sheath helix structure is assumed to exist at the outer surface of cylinder. The effects of sheath helix orientation, along with the material parameters, such as chirality admittance and gyrotropy, on the echo width as well as the magnitude and phase of the electric and magnetic fields are investigated. Control on the anisotropic property remains greatly useful in obtaining the required optical response from the scatterer - the feature which would find fabulous sensing related applications.

  3. Current Status of TRR-1/M1

    International Nuclear Information System (INIS)

    Sittichai, Chaiyut

    2000-01-01

    In 1961, the first Thai Research Reactor, TRR-1, having power of 1 MW was established. It was located at Office of Atomic Energy for Peace (OAEP) in Bangkok. TRR-1 was completely commissioned in June 1962. Plate typed high-enriched uranium (HEU) and U 3 O 8 -Al were used as fuel. Light water used as moderator and coolant. During 1975-1977, TRR-1 was shut down for modification. The reactor core and control system were disassembled and replaced by TRIGA Mark III. It is a circular hexagonal core typed reactor designed by General Atomics Company (GA). Afterwards, TRR-1 was officially renamed to Thai Research Reactor 1/Modification 1 (TRR-1/M1). TRR-1/M1 is a multipurpose reactor with nominal power of 2 MW. This swimming pool typed reactor uses low-enriched uranium (LEU) as fuel and light water as coolant and moderator. To date, the reactor has been operated with core No.12 that released power 1135 MWD to serve the user. The reactor has been serving for various kinds of utilization, for example, to produce radioisotope, neutron beam experiments and reactor physics experiments. This report explains in detail regarding operational experience and current status of this reactor, for example, reactor operation and reactor utilization. (author)

  4. "m=1" coatings for neutron guides

    DEFF Research Database (Denmark)

    Cooper-Jensen, C.P.; Vorobiev, A.; Klinkby, Esben Bryndt

    2014-01-01

    A substantial part of the price for a neutron guide is the shielding needed because of the gamma ray produced when neutrons are absorbed. This absorption occurs in the coating and the substrate of the neutron guides. Traditional m=1 coatings have been made of Ni and if reflectivity over...... the critical angle of Ni is needed one has used Ni58 or Ni/Ti multilayer coatings. Ni has one of the highest neutron scattering density but it also has a fairly high absorption cross section for cold and thermal neutrons and when a neutron is absorbed it emits a lot of gamma rays, some with energies above 9 Me...... of diamond coatings to show the potential for using these coatings in neutron guides....

  5. E-ELT M1 test facility

    Science.gov (United States)

    Dimmler, M.; Marrero, J.; Leveque, S.; Barriga, P.; Sedghi, B.; Mueller, M.

    2012-09-01

    During the advanced design phase of the European Extremely Large Telescope (E-ELT) several critical components have been prototyped. During the last year some of them have been tested in dedicated test stands. In particular, a representative section of the E-ELT primary mirror has been assembled with 2 active and 2 passive segments. This test stand is equipped with complete prototype segment subunits, i.e. including support mechanisms, glass segments, edge sensors, position actuators as well as additional metrology for monitoring. The purpose is to test various procedures such as calibration, alignment and handling and to study control strategies. In addition the achievable component and subsystem performances are evaluated, and interface issues are identified. In this paper an overview of the activities related to the E-ELT M1 Test Facility will be given. Experiences and test results are presented.

  6. Introduction to the m = 1 helicity source

    International Nuclear Information System (INIS)

    Platts, D.A.; Jarboe, T.R.; Wright, B.L.

    1985-01-01

    The m = 1 Helicity Source, formerly called the Kinked Z-pinch, was developed as part of the Electrode Studies program at Los Alamos. The Electrode Studies program was initiated to study the control of electrode erosion in long discharge duration spheromak sources. Erosion control is necessary to reduce plasma impurities and to obtain adequate electrode lifetimes. The first task of the Electrode Studies program is to determine, from among a variety of configurations including the coaxial one, a helicity source geometry with good prospects for erosion control. The more efficient the helicity source the easier it will be to control erosion, but the source most also be easy to diagnose and modify if it is to be a useful test bed. The various erosion control techniques which have been proposed will require extensive experimentation to evaluate and optimize. Proposed techniques include, using refractory metals, profiling of the electrodes and magnetic fields, and various gas injection schemes including porous electrodes. It is considered necessary to do these experiments on an optimized helicity source so that the electrode geometries and plasma properties will be relevant. Therefore the present Electrode Studies program is aimed at developing an improved helicity source design

  7. Field and laboratory evidence that Bungowannah virus, a recently recognised pestivirus, is the causative agent of the porcine myocarditis syndrome (PMC).

    Science.gov (United States)

    Finlaison, Deborah S; King, Katherine R; Frost, Melinda J; Kirkland, Peter D

    2009-05-12

    In 2003 an outbreak of sudden deaths occurred in 2-3-week-old piglets on a piggery in New South Wales, Australia. There was a marked increase in the birth of stillborn piglets and preweaning losses associated with a multifocal non-suppurative myocarditis with myonecrosis. The aim of this study was to review existing data and to undertake further investigations of specimens from naturally infected pigs to provide evidence to support the hypothesis that Bungowannah virus, a recently recognised pestivirus, causes the porcine myocarditis syndrome (PMC). Sera collected from gilts and sows from affected and unaffected units were tested for Bungowannah virus antibody by a peroxidase-linked assay and Bungowannah virus RNA by qRT-PCR in selected cases. Stillborn piglets from affected and an unaffected unit were also tested for Bungowannah virus antibody and RNA. Body fluid IgG levels and the incidence of myocardial lesions in these stillborn piglets are summarised. Tissue sections from stillborn piglets with myocarditis/myonecrosis were examined for Bungowannah virus RNA by in situ hybridisation. A clear temporal association between the occurrence of PMC on a unit or module and exposure to Bungowannah virus was identified by serological tests in both breeding aged animals and stillborn pigs. In addition, at the individual animal level on affected units, Bungowannah virus RNA was detected in stillborn piglets in large amounts by qRT-PCR and in association with myocardial lesions by in situ hybridisation. The examination of field material from cases of PMC by serology, qRT-PCR and in situ hybridisation provides strong indirect evidence that Bungowannah virus is the causative agent for PMC.

  8. Transcranial Direct Current Stimulation over the Medial Prefrontal Cortex and Left Primary Motor Cortex (mPFC-lPMC) Affects Subjective Beauty but Not Ugliness

    Science.gov (United States)

    Nakamura, Koyo; Kawabata, Hideaki

    2015-01-01

    Neuroaesthetics has been searching for the neural bases of the subjective experience of beauty. It has been demonstrated that neural activities in the medial prefrontal cortex (mPFC) and the left primary motor cortex (lPMC) correlate with the subjective experience of beauty. Although beauty and ugliness seem to be semantically and conceptually opposite, it is still unknown whether these two evaluations represent extreme opposites in unitary or bivariate dimensions. In this study, we applied transcranial direct current stimulation (tDCS) to examine whether non-invasive brain stimulation modulates two types of esthetic evaluation; evaluating beauty and ugliness. Participants rated the subjective beauty and ugliness of abstract paintings before and after the application of tDCS. Application of cathodal tDCS over the mPFC with anode electrode over the lPMC, which induced temporal inhibition of neural excitability of the mPFC, led to a decrease in beauty ratings but not ugliness ratings. There were no changes in ratings of both beauty and ugliness when applying anodal tDCS or sham stimulation over the mPFC. Results from our experiment indicate that the mPFC and the lPMC have a causal role in generating the subjective experience of beauty, with beauty and ugliness evaluations constituting two distinct dimensions. PMID:26696865

  9. Infinitely many N=1 dualities from m+1m=1

    Energy Technology Data Exchange (ETDEWEB)

    Agarwal, Prarit; Intriligator, Kenneth; Song, Jaewon [Department of Physics, University of California,San Diego, La Jolla, CA 92093 (United States)

    2015-10-06

    We discuss two infinite classes of 4d supersymmetric theories, T{sub N}{sup (m)} and U{sub N}{sup (m)}, labelled by an arbitrary non-negative integer, m. The T{sub N}{sup (m)} theory arises from the 6d, A{sub N−1} type N=(2,0) theory reduced on a 3-punctured sphere, with normal bundle given by line bundles of degree (m+1,−m); the m=0 case is the N=2 supersymmetric T{sub N} theory. The novelty is the negative-degree line bundle. The U{sub N}{sup (m)} theories likewise arise from the 6d N=(2,0) theory on a 4-punctured sphere, and can be regarded as gluing together two (partially Higgsed) T{sub N}{sup (m)} theories. The T{sub N}{sup (m)} and U{sub N}{sup (m)} theories can be represented, in various duality frames, as quiver gauge theories, built from T{sub N} components via gauging and nilpotent Higgsing. We analyze the RG flow of the U{sub N}{sup (m)} theories, and find that, for all integer m>0, they end up at the same IR SCFT as SU(N) SQCD with 2N flavors and quartic superpotential. The U{sub N}{sup (m)} theories can thus be regarded as an infinite set of UV completions, dual to SQCD with N{sub f}=2N{sub c}. The U{sub N}{sup (m)} duals have different duality frame quiver representations, with 2m+1 gauge nodes.

  10. M1 transitions in the (sdg) boson model

    International Nuclear Information System (INIS)

    Kuyucak, S.; Tuebingen Univ.; Morrison, I.

    1988-01-01

    Using the 1/N expansion technique we derive expressions for β → g, γ → g and γ → γ M1 transitions in a general boson model. The M1 matrix elements in the sdg-boson model are similar in form to those in the neutron-proton IBM. Comparisons are made to some selected M1 data exhibiting collective character. (orig.)

  11. M1 transitions in the (sdg) boson model

    Energy Technology Data Exchange (ETDEWEB)

    Kuyucak, S.; Morrison, I.

    1988-03-03

    Using the 1/N expansion technique we derive expressions for ..beta.. -> g, ..gamma.. -> g and ..gamma.. -> ..gamma.. M1 transitions in a general boson model. The M1 matrix elements in the sdg-boson model are similar in form to those in the neutron-proton IBM. Comparisons are made to some selected M1 data exhibiting collective character.

  12. Stochasticity and the m = 1 mode in tokamaks

    International Nuclear Information System (INIS)

    Izzo, R.; Monticello, D.A.; Stodiek, W.; Park, W.

    1986-05-01

    It has recently been proposed that stochasticity resulting from toroidal coupling could lead to a saturation of the m = 1 internal mode in tokamaks. We present results from the nonlinear evolution of the m = 1 mode with toroidal coupling that show that stochasticity is not enough to cause saturation of the m = 1 mode

  13. M1 transitions in the (sdg) boson model

    Science.gov (United States)

    Kuyucak, S.; Morrison, I.

    1988-03-01

    Using the {1}/{N} expansion technique we derive expressions for β→g, γ→g and γ→γ M1 transitions in a general boson model. The M1 matrix elements in the sdg-boson model are similar in form to those in the neutron-proton IBM. Comparisons are made to some selected M1 data exhibiting collective character.

  14. Symbiotic nature of the object M1-77

    International Nuclear Information System (INIS)

    Kondrt'eva, L.N.

    2004-01-01

    Many year spectral observations show, that the object M1-77 is the symbiotic system, which consists of a M-giant and a B-star. An emission spectra arises from an envelope, which was formed from a giant's extended atmosphere, and now is ionized by the hotter component. Some spectral changes were registered in M1-77: the forbidden lines intensities increase relatively to that of Hα. It is connected with the decrease of hydrogen emission. (author)

  15. Investigation of aflatoxin M1 degradation in milk

    Directory of Open Access Journals (Sweden)

    Smajlović Ahmed

    2012-01-01

    Full Text Available Aflatoxin M1 is a highly toxic 4-hydroxylated metabolite of aflatoxins B1 and B2. It is one of the most potent hepatocarcinogens, mutagens, teratogens and immunosuppressors. Feed is often contaminated with aflatoxigenic moulds and aflatoxins with a high possibility of contaminating milk and dairy products with aflatoxin M1. Samples of artificially contaminated milk were exposed to the effects of physical conditions (temperature of -18oC and for microwaves in a microwave oven, time (during the period from 1 to 12 months and a combination of the above mentioned conditions. Following this, levels of aflatoxin M1 degradation were established by using the ELISA method. An insignificant decrease in concentration of toxin was observed which indicates that a temperature of -18°C does not significantly influence the concentration of aflatoxin M1 in the artificially contaminated milk. At the same time, treatment of milk with microwaves in a microwave oven showed an insignificant influence on the percentage of aflatoxin M1 absorbance.

  16. Influence of extracellular zinc on M1 microglial activation.

    Science.gov (United States)

    Higashi, Youichirou; Aratake, Takaaki; Shimizu, Shogo; Shimizu, Takahiro; Nakamura, Kumiko; Tsuda, Masayuki; Yawata, Toshio; Ueba, Tetuya; Saito, Motoaki

    2017-02-27

    Extracellular zinc, which is released from hippocampal neurons in response to brain ischaemia, triggers morphological changes in microglia. Under ischaemic conditions, microglia exhibit two opposite activation states (M1 and M2 activation), which may be further regulated by the microenvironment. We examined the role of extracellular zinc on M1 activation of microglia. Pre-treatment of microglia with 30-60 μM ZnCl 2 resulted in dose-dependent increases in interleukin-1 beta (IL-1β), interleukin-6 (IL-6), and tumour necrosis factor-alpha (TNFα) secretion when M1 activation was induced by lipopolysaccharide administration. In contrast, the cell-permeable zinc chelator TPEN, the radical scavenger Trolox, and the P2X7 receptor antagonist A438079 suppressed the effects of zinc pre-treatment on microglia. Furthermore, endogenous zinc release was induced by cerebral ischaemia-reperfusion, resulting in increased expression of IL-1β, IL-6, TNFα, and the microglial M1 surface marker CD16/32, without hippocampal neuronal cell loss, in addition to impairments in object recognition memory. However, these effects were suppressed by the zinc chelator CaEDTA. These findings suggest that extracellular zinc may prime microglia to enhance production of pro-inflammatory cytokines via P2X7 receptor activation followed by reactive oxygen species generation in response to stimuli that trigger M1 activation, and that these inflammatory processes may result in deficits in object recognition memory.

  17. M1 transitions between superdeformed states in 195Tl

    International Nuclear Information System (INIS)

    Zheng Xing; Xingqu Chen; Xiaochun Wang

    1996-01-01

    Using a triaxial-particle-rotor model, the quadrupole and dipole transition energies, kinematic and dynamic moments of inertia, electromagnetic transition probabilities and the relative intensity of the E2 γ-transitions are calculated for superdeformed bands in 195 Tl. A strong perturbation effect of rotation on transition energies and M1 and E2 transitions of superdeformed states is investigated. The total M1 transitions, enhanced by internal conversion, are expected to compete strongly with the E2 γ-ray at low spins in the superdeformed 195 Tl nucleus. (author)

  18. M1-transitions in the MIT bag model

    International Nuclear Information System (INIS)

    Hackman, R.H.; Deshpande, N.G.; Dicus, D.A.; Teplitz, V.L.

    1977-03-01

    In the MIT bag model, the M1-transitions of low lying hadrons are investigated. The following calculations are performed: 32 hadron masses are recomputed with a choice of bag parameters designed to give the correct values for the proton magnetic moment, μ/sub p/, and several masses, M/sub rho/ M/sub ω/ M/sub Δ/ M/sub Ω/, and M/sub D/; (2) eta, eta', eta/sub c/ mixing is computed in an untrustworthy approximation; and the widths for 38 M1-transitions are computed

  19. Genetic analysis of rice semidwarf mutant Tad-M-1

    International Nuclear Information System (INIS)

    Wang Naiyuan; Yang Rencui

    1995-01-01

    This paper dealed with the inheritance of the rice semidwarf of Tad-M-,a mutant line bred from traditional indica rice Variety Tadukan by radiation. The results indicated that semidwarf of Tad-M-1 was controlled by one pair of recessive gene, which was nonallelic to sd-1 gene of variety Aijiaonante and sd-g gene of variety Xinguiai and allelic to the semidwarf gene of Yunnan japonica variety Xueheaizao and Sichuan indica variety Yizila.The possible uses of Tad-M-1 in rice breeding was also discussed

  20. assessing aflatoxin m1 levels among lactating mothers' in damaturu ...

    African Journals Online (AJOL)

    userpc

    1Department of Microbiology Ahmadu Bello University Zaria, Kaduna State. ... Aflatoxin M1 (AFM1) is a biomarker of aflatoxin B1 exposure in breast milk, a possible risk factor for infant early ..... Mycotoxins in food and feed: present status and ...

  1. Analytic theory of the nonlinear M = 1 tearing mode

    International Nuclear Information System (INIS)

    Hazeltine, R.D.; Meiss, J.D.; Morrison, P.J.

    1985-09-01

    Numerical studies show that the m = 1 tearing mode continues to grow exponentially well into the nonlinear regime, in contrast with the slow, ''Rutherford,'' growth of m > 1 modes. We present a single helicity calculation which generalizes that of Rutherford to the case when the constant-psi approximation is invalid. As in that theory, the parallel current becomes an approximate flux function when the island size, W, exceeds the linear tearing layer width. However for the m = 1 mode, W becomes proportional to deltaB, rather than (deltaB)/sup 1/2/ above this critical amplitude. This implies that the convective nonlinearity in Ohm's law, which couples the m = 0 component to the m = 1 component, dominates the resistive diffusion term. The balance between the inductive electric field and this convective nonlinearity results in exponential growth. Assuming the form of the perturbed fields to be like that of the linear mode, we find that the growth occurs at 71% of the linear rate

  2. Theory of the m=1 kink mode in toroidal plasmas

    International Nuclear Information System (INIS)

    Blank, J.H. de.

    1990-01-01

    The work in this thesis addresses the stability problems arising in tokamak experiments. In part I of this thesis the internal m=1 kink instability in tokamak plasmas is considered within the confines of ideal magnetohydrodynamics (ideal MHD), in which model the pressure is considered to be isotropic, while state is assumed. Because irreversible processes are disregarded, there is an energy principle. By extremizing the energy associated with infinitesimal perturbations of the plasma, a normal mode is obtained. The m=n=1 mode is resonant at the q=1 surface, and therefore, equilibria with a broad region where q#approx = # 1 are expected to be particularly unstable. The m=1 instability is computed for these q profiles. In Part II of this thesis, the internal m=1 kink instability is considered in a stationary rotating tokamak plasma, in which the particle velocity distribution is allowed to be non-thermal. In a tokamak plasma that is intensely heated by neutron beams or radiofrequent waves, these features, which cannot be described with ideal MHD, may become important, especially in the cases with high m=1 growth rates found in Part I. The energy principle of a generalized fluid theory is applied in these cases, without specifying the equation of state of the plasma. Therefore the resulting energy functional for the m=1 mode is incomplete and not direct applicable, however, the result makes clear that a kinetic description of the plasma is required only to a first approximation, and can therefore be applied analytically. The guiding center approximation is applied, which neglects finite gyroradius effects and collisions. Application of the dispersion relation, that is obtained from kinetic theory, shows that compared to the ideal MHD case, growth rates are strongly reduced due to Landau damping while the stability boundaries are not changed. (author). 72 refs.; 11 figs

  3. Quadrupole decay strength of the M1 scissors mode

    Science.gov (United States)

    Beck, T.; Beller, J.; Derya, V.; Gayer, U.; Isaak, J.; Löher, B.; Mertes, L.; Pietralla, N.; Ries, P.; Romig, C.; Savran, D.; Scheck, M.; Tornow, W.; Weller, H. R.; Werner, V.; Zweidinger, M.

    2015-10-01

    The E2/M1 multipole mixing ratio δ1→2 of the 1sc +→21+ transition of Gd was determined using results from high-statistics photon scattering. This provides a possibility for a new approach on the search of Jsc + members of the rotational band built on the scissors mode. By application of Alaga's rule, which is justifiable as 156Gd is a well-deformed rotor with good K quantum number, a transition strength of B (E 2 ;2sc +→01+)=0.034 (13 ) W.u. is estimated.

  4. Flavonoids with M1 Muscarinic Acetylcholine Receptor Binding Activity

    Directory of Open Access Journals (Sweden)

    Meyyammai Swaminathan

    2014-06-01

    Full Text Available Muscarinic acetylcholine receptor-active compounds have potential for the treatment of Alzheimer’s disease. In this study, a series of natural and synthetic flavones and flavonols was assayed in vitro for their ability to inhibit radioligand binding at human cloned M1 muscarinic receptors. Several compounds were found to possess competitive binding affinity (Ki = 40–110 µM, comparable to that of acetylcholine (Ki = 59 µM. Despite the fact that these compounds lack a positively-charged ammonium group under physiological conditions, molecular modelling studies suggested that they bind to the orthosteric site of the receptor, mainly through non-polar interactions.

  5. PEMBUATAN PROGRAM INTERFACE UNTUK PENGONTROLAN RV-M1

    Directory of Open Access Journals (Sweden)

    Endra Endra

    2007-10-01

    Full Text Available Article explores the making of interface of RV-M1 hand robot control that replaced the cosiprog program,a program that is able to help student in Mecatronica-1 Practice, and able to control the hand robot by localnetwork by two user or more. The used methods were literature study, and field study, that is design method. Theresearch result are control of hand robot on X,Y,Z axis and point to point, the use of local network to control thehand robot, save certain position, and use several user to control the robot.Keywords: interface program, robot, local network

  6. Characterization of pMC11, a plasmid with dual origins of replication isolated from Lactobacillus casei MCJ and construction of shuttle vectors with each replicon

    DEFF Research Database (Denmark)

    Chen, Zhengjun; Lin, Jinzhong; Ma, Chengjie

    2014-01-01

    . These plasmids showed distinct properties: pEL5.7 was capable of replicating in L. casei MCJΔ1 and Lactobacillus delbrueckii subsp. lactic LBCH-1 but failed to do so in two other tested lactobacilli strains whereas pEL5.6 replicated in three different strains, including L. casei MCJΔ1, L. casei NJ, Lactobacillus......Many lactic acid bacteria carry different plasmids, particularly those that replicate via a theta mechanism. Here we describe Lactobacillus casei MCJ(CCTCC AB20130356), a new isolate that contains pMC11, carrying two distinct theta-type replicons. Each replicon contained an iteron in the origin...... of replication (oriV1 or oriV2) and a gene coding for the replicase (RepA_1 or RepB_1), both of which are essential for plasmid replication. Escherichia coli/Lactobacillus shuttle vectors were constructed with each replicon, yielding pEL5.7 and pEL5.6 that are based on oriV2 and oriV1 replicons, respectively...

  7. E1 and M1 strength functions at low energy

    Science.gov (United States)

    Schwengner, Ronald; Massarczyk, Ralph; Bemmerer, Daniel; Beyer, Roland; Junghans, Arnd R.; Kögler, Toni; Rusev, Gencho; Tonchev, Anton P.; Tornow, Werner; Wagner, Andreas

    2017-09-01

    We report photon-scattering experiments using bremsstrahlung at the γELBE facility of Helmholtz-Zentrum Dresden-Rossendorf and using quasi-monoenergetic, polarized γ beams at the HIγS facility of the Triangle Universities Nuclear Laboratory in Durham. To deduce the photoabsorption cross sections at high excitation energy and high level density, unresolved strength in the quasicontinuum of nuclear states has been taken into account. In the analysis of the spectra measured by using bremsstrahlung at γELBE, we perform simulations of statistical γ-ray cascades using the code γDEX to estimate intensities of inelastic transitions to low-lying excited states. Simulated average branching ratios are compared with model-independent branching ratios obtained from spectra measured by using monoenergetic γ beams at HIγS. E1 strength in the energy region of the pygmy dipole resonance is discussed in nuclei around mass 90 and in xenon isotopes. M1 strength in the region of the spin-flip resonance is also considered for xenon isotopes. The dipole strength function of 74Ge deduced from γELBE experiments is compared with the one obtained from experiments at the Oslo Cyclotron Laboratory. The low-energy upbend seen in the Oslo data is interpreted as M1 strength on the basis of shell-model calculations.

  8. E1 and M1 strength functions at low energy

    Directory of Open Access Journals (Sweden)

    Schwengner Ronald

    2017-01-01

    Full Text Available We report photon-scattering experiments using bremsstrahlung at the γELBE facility of Helmholtz-Zentrum Dresden-Rossendorf and using quasi-monoenergetic, polarized γ beams at the HIγS facility of the Triangle Universities Nuclear Laboratory in Durham. To deduce the photoabsorption cross sections at high excitation energy and high level density, unresolved strength in the quasicontinuum of nuclear states has been taken into account. In the analysis of the spectra measured by using bremsstrahlung at γELBE, we perform simulations of statistical γ-ray cascades using the code γDEX to estimate intensities of inelastic transitions to low-lying excited states. Simulated average branching ratios are compared with model-independent branching ratios obtained from spectra measured by using monoenergetic γ beams at HIγS. E1 strength in the energy region of the pygmy dipole resonance is discussed in nuclei around mass 90 and in xenon isotopes. M1 strength in the region of the spin-flip resonance is also considered for xenon isotopes. The dipole strength function of 74Ge deduced from γELBE experiments is compared with the one obtained from experiments at the Oslo Cyclotron Laboratory. The low-energy upbend seen in the Oslo data is interpreted as M1 strength on the basis of shell-model calculations.

  9. Presence of moulds and aflatoxin M1 in milk

    Directory of Open Access Journals (Sweden)

    Janković Vesna V.

    2009-01-01

    Full Text Available Aflatoxin M1 (AFM1 appears in milk or dairy products as a direct result of the cattle's ingestion of feed contaminated with aflatoxin B1 (AFB1. This study comprises mycological and mycotoxicological investigations of 23 milk samples (raw, infant food, pasteurized, whey and yoghurt. The mycological testing showed dominant presence of genus Geotrichum. G. candidum was found in 9 samples, with the highest contamination in the raw milk samples. The contamination level of AM1 is defined by using direct competitive enzyme- -linked immunosorbent assay (ELISA. AFM1 was found in 9 samples. AFM1 levels were lower than the recommended limits. However, as AFM1 is considered a probable human carcinogen (2B type, it is necessary to achieve a low level of AFM1 in milk. Therefore, cows' feed samples from various cowsheds are supposed to be evaluated routinely for aflatoxin, and kept away from fungal contamination as much as possible.

  10. Interference effects in Moessbauer spectra of M1-transitions

    International Nuclear Information System (INIS)

    Peregudov, V.N.

    1980-01-01

    The purpose of the study is the calculation of interference effects in Moessbauer spectra of the (γ, e) reaction. Two channels of the inelastic (γ, e) reaction are considered: resonance gamma radiation absorption by nucleus accompanied by internal conversion and photo absorption by atomic electrons. The case of M1 nuclear transition multipolarity is considered. The expression for angular dependence coefficients of interference member is obtained. General expression for (γ, e) reaction cross section is obtained in a long-wave approximation for the case when the specimen is placed in longitudinal magnetic field involving superfine nuclear level splitting. The results of disperse amplitudes calculation for 93 Kr, 119 Sn, 129 I, 149 Sm, 151 Eu, 169 Tm, 183 W, 193 Ir, 197 Au nuclei are verified. The calculations show that maximum interference effect in the (γ, e) reaction should be expected for 169 Tm isotope [ru

  11. Excitation of M1 resonances by medium energy protons

    International Nuclear Information System (INIS)

    Crawley, G.M.; Djalali, C.; Marty, N.

    1983-01-01

    The results of 201 MeV (p,p') studies of ΔL=0 spin-flip transitions at very forward angles are discussed. The reasons for making comparisons between (p,p'), (p,n) and electromagnetic measurements of M1 transitions are outlined. After presenting some of the experimental and theoretical uncertainties, a summary of the results on the Zr isotopes plus other nuclei to mass 140 is given. Results from 48 Ca, the N=28 nuclei 50 Ti, 51 V, 52 Cr and 54 Fe are discussed and compared with (p,n) and electromagnetic measurements. In the Ni isotopes, the T 0 and T 0 +1 components of the 1 + spin-flips transition were observed both in (p,p') and in (p,n) reactions

  12. Thai Research Reactor (TRR-1/M1) Neutron Beam Measurements

    International Nuclear Information System (INIS)

    Ratanatongchai, Wichian

    2009-07-01

    Full text: Neutron beam tube of neutron radiography facility at Thai Research Reactor (TRR-1/M1) Thailand Institute of Nuclear Technology (public organization) is a divergent beam. The rectangular open-end of the beam tube is 16 cm x 17 cm while the inner-end is closed to the reactor core. The neutron beam size was measured using 20 cm x 40 cm neutron imaging plate. The measurement at the position 100 cm from the end of the collimator has shown that the beam size was 18.2 cm x 19.0 cm. Gamma ray in neutron the beam was also measured by the identical position using industrial X ray film. The area of gamma ray was 27.8 cm x 31.1 cm with the highest intensity found to be along the neutron beam circumference

  13. Aflatoxin M1 Contamination in Ice-Cream

    Directory of Open Access Journals (Sweden)

    R. Kazemi Darsanaki

    2013-06-01

    Full Text Available Aflatoxin M1 (AFM1 is the hydroxylated metabolite of aflatoxin B1 (AFB1 that it can be found in milk and dairy products. In this study, ELISA (Enzyme Linked Immunosorbent Assay technique was used for detection of AFM1 in ice-cream in Guilan province (Northern Iran. A total of 90 ice-cream samples was randomly obtained from different supermarkets. In 62 of the 90 ice-cream samples examined (68.88%, the presence of AFM1 was detected in concentrations between 8.4 -147.7 ng/l. The mean level of AFM1 in positive samples was 40.36 ng/l. AFM1 levels in 11 samples (12.22% were higher than the maximum tolerance limit (50 ng/l accepted by ISIRI, European Community and Codex Alimentarius.

  14. Reduction of Aflatoxin M1 in Milk Using Kefir Starter

    Directory of Open Access Journals (Sweden)

    Siavash Kamyar

    2017-11-01

    Full Text Available Background: Mycotoxins naturally occur in foods. Aflatoxins can cause serious health problems in consumers. Nowadays, biological detoxification method is considered to decrease the aflatoxins level in foods. The aim of this study was to evaluate the effect of kefir starter microorganisms to decrease the aflatoxin M1 (AFM1 levels in milk. Methods: The study was carried out at Shabestar branch, Islamic Azad University in 2016. AFM1 at three levels 150, 200 and 250 ng/L was added to milk samples. Then a pool of lactic acid bacteria (LAB, yeasts and full kefir starter culture was added to milk samples. After cool storage of samples in 4 °C for 7 d, all samples were collected and the level of AFM1 determined by HPLC method. All samples were prepared in triplicate. Results: The highest reduction percentage of AFM1 was observed in yeast (65.33%-68.89% and LAB pool (65%. Samples with full kefir starter showed the reduction percent range of 11.67-34.66% that was lower in compare with other treatment groups. Conclusion: These findings support the ability of LAB and yeasts to bind to aflatoxins in foods. Kefir drink in countries with high contamination by AFM1 in milk can be a safe dairy product choice for consumers.

  15. High-definition transcranial direct-current stimulation of the right M1 further facilitates left M1 excitability during crossed facilitation.

    Science.gov (United States)

    Cabibel, Vincent; Muthalib, Makii; Teo, Wei-Peng; Perrey, Stephane

    2018-04-01

    The crossed-facilitation (CF) effect refers to when motor-evoked potentials (MEPs) evoked in the relaxed muscles of one arm are facilitated by contraction of the opposite arm. The aim of this study was to determine whether high-definition transcranial direct-current stimulation (HD-tDCS) applied to the right primary motor cortex (M1) controlling the left contracting arm [50% maximum voluntary isometric contraction (MVIC)] would further facilitate CF toward the relaxed right arm. Seventeen healthy right-handed subjects participated in an anodal and cathodal or sham HD-tDCS session of the right M1 (2 mA for 20 min) separated by at least 48 h. Single-pulse transcranial magnetic stimulation (TMS) was used to elicit MEPs and cortical silent periods (CSPs) from the left M1 at baseline and 10 min into and after right M1 HD-tDCS. At baseline, compared with resting, CF (i.e., right arm resting, left arm 50% MVIC) increased left M1 MEP amplitudes (+97%) and decreased CSPs (-11%). The main novel finding was that right M1 HD-tDCS further increased left M1 excitability (+28.3%) and inhibition (+21%) from baseline levels during CF of the left M1, with no difference between anodal and cathodal HD-tDCS sessions. No modulation of CSP or MEP was observed during sham HD-tDCS sessions. Our findings suggest that CF of the left M1 combined with right M1 anodal or cathodal HD-tDCS further facilitated interhemispheric interactions during CF from the right M1 (contracting left arm) toward the left M1 (relaxed right arm), with effects on both excitatory and inhibitory processing. NEW & NOTEWORTHY This study shows modulation of the nonstimulated left M1 by right M1 HD-tDCS combined with crossed facilitation, which was probably achieved through modulation of interhemispheric interactions.

  16. M1 and M2 Monocytes in Rheumatoid Arthritis: A Contribution of Imbalance of M1/M2 Monocytes to Osteoclastogenesis

    Directory of Open Access Journals (Sweden)

    Shoichi Fukui

    2018-01-01

    Full Text Available ObjectivesWe investigated the relationships among M1 monocytes, M2 monocytes, osteoclast (OC differentiation ability, and clinical characteristics in patients with rheumatoid arthritis (RA.MethodsPeripheral blood mononuclear cells (PBMCs were isolated from RA patients and healthy donors, and we then investigated the number of M1 monocytes or M2 monocytes by fluorescence-activated cell sorting. We also obtained and cultured CD14-positive cells from PBMCs from RA patients and healthy donors to investigate OC differentiation in vitro.ResultsForty RA patients and 20 healthy donors were included. Twenty-two patients (55% were anticitrullinated protein antibody (ACPA positive. The median M1/M2 ratio was 0.59 (0.31–1.11, interquartile range. There were no significant differences between the RA patients and healthy donors. There was a positive correlation between the M1/M2 ratio and the differentiated OC number in vitro in RA patients (ρ = 0.81, p < 0.001. The ACPA-positive patients had significantly higher M1/M2 ratios in vivo (p = 0.028 and significantly greater numbers of OCs in vitro (p = 0.005 than the ACPA-negative patients. Multivariable regression analysis revealed that the M1/M2 ratio was the sole significant contribution factor to in vitro osteoclastogenesis. RA patients with M1/M2 ratios >1 (having relatively more M1 monocytes had higher C-reactive protein and erythrocyte sedimentation rates than RA patients with M1/M2 ratios ≤1. M1-dominant monocytes in vitro produced higher concentrations of interleukin-6 upon stimulation with lipopolysaccharide than M2 monocytes.ConclusionM1/M2 monocytes imbalance strongly contributes to osteoclastogenesis of RA patients. Our findings cast M1 and M2 monocyte subsets in a new light as a new target of treatments for RA to prevent progression of osteoclastic bone destruction.

  17. Modification of barley powdery mildew resistance controlled by the gene M1-a212

    International Nuclear Information System (INIS)

    Torp, J.; Joergensen, J.H.

    1989-01-01

    Full text: The barley line Sultan 5 carries resistance gene M1-a12. Seeds were treated with EMS or NaN 3 . Among 10381 M 1 -spike progenies inoculated with M1-a12 a-virulent isolates of Erysiphe graminis, 25 segregated for less resistant infection type. Among 10 mutants analyzed, 9 had mutant allels of M1-a12 and one had a recessive mutant gene in a different locus acting as a ''suppressor'' of M1-a12. (author)

  18. Staurosporine augments EGF-mediated EMT in PMC42-LA cells through actin depolymerisation, focal contact size reduction and Snail1 induction – A model for cross-modulation

    International Nuclear Information System (INIS)

    Hugo, Honor J; Wafai, Razan; Blick, Tony; Thompson, Erik W; Newgreen, Donald F

    2009-01-01

    A feature of epithelial to mesenchymal transition (EMT) relevant to tumour dissemination is the reorganization of actin cytoskeleton/focal contacts, influencing cellular ECM adherence and motility. This is coupled with the transcriptional repression of E-cadherin, often mediated by Snail1, Snail2 and Zeb1/δEF1. These genes, overexpressed in breast carcinomas, are known targets of growth factor-initiated pathways, however it is less clear how alterations in ECM attachment cross-modulate to regulate these pathways. EGF induces EMT in the breast cancer cell line PMC42-LA and the kinase inhibitor staurosporine (ST) induces EMT in embryonic neural epithelial cells, with F-actin de-bundling and disruption of cell-cell adhesion, via inhibition of aPKC. PMC42-LA cells were treated for 72 h with 10 ng/ml EGF, 40 nM ST, or both, and assessed for expression of E-cadherin repressor genes (Snail1, Snail2, Zeb1/δEF1) and EMT-related genes by QRT-PCR, multiplex tandem PCR (MT-PCR) and immunofluorescence +/- cycloheximide. Actin and focal contacts (paxillin) were visualized by confocal microscopy. A public database of human breast cancers was assessed for expression of Snail1 and Snail2 in relation to outcome. When PMC42-LA were treated with EGF, Snail2 was the principal E-cadherin repressor induced. With ST or ST+EGF this shifted to Snail1, with more extreme EMT and Zeb1/δEF1 induction seen with ST+EGF. ST reduced stress fibres and focal contact size rapidly and independently of gene transcription. Gene expression analysis by MT-PCR indicated that ST repressed many genes which were induced by EGF (EGFR, CAV1, CTGF, CYR61, CD44, S100A4) and induced genes which alter the actin cytoskeleton (NLF1, NLF2, EPHB4). Examination of the public database of breast cancers revealed tumours exhibiting higher Snail1 expression have an increased risk of disease-recurrence. This was not seen for Snail2, and Zeb1/δEF1 showed a reverse correlation with lower expression values being predictive

  19. Staurosporine augments EGF-mediated EMT in PMC42-LA cells through actin depolymerisation, focal contact size reduction and Snail1 induction – A model for cross-modulation

    Directory of Open Access Journals (Sweden)

    Thompson Erik W

    2009-07-01

    Full Text Available Abstract Background A feature of epithelial to mesenchymal transition (EMT relevant to tumour dissemination is the reorganization of actin cytoskeleton/focal contacts, influencing cellular ECM adherence and motility. This is coupled with the transcriptional repression of E-cadherin, often mediated by Snail1, Snail2 and Zeb1/δEF1. These genes, overexpressed in breast carcinomas, are known targets of growth factor-initiated pathways, however it is less clear how alterations in ECM attachment cross-modulate to regulate these pathways. EGF induces EMT in the breast cancer cell line PMC42-LA and the kinase inhibitor staurosporine (ST induces EMT in embryonic neural epithelial cells, with F-actin de-bundling and disruption of cell-cell adhesion, via inhibition of aPKC. Methods PMC42-LA cells were treated for 72 h with 10 ng/ml EGF, 40 nM ST, or both, and assessed for expression of E-cadherin repressor genes (Snail1, Snail2, Zeb1/δEF1 and EMT-related genes by QRT-PCR, multiplex tandem PCR (MT-PCR and immunofluorescence +/- cycloheximide. Actin and focal contacts (paxillin were visualized by confocal microscopy. A public database of human breast cancers was assessed for expression of Snail1 and Snail2 in relation to outcome. Results When PMC42-LA were treated with EGF, Snail2 was the principal E-cadherin repressor induced. With ST or ST+EGF this shifted to Snail1, with more extreme EMT and Zeb1/δEF1 induction seen with ST+EGF. ST reduced stress fibres and focal contact size rapidly and independently of gene transcription. Gene expression analysis by MT-PCR indicated that ST repressed many genes which were induced by EGF (EGFR, CAV1, CTGF, CYR61, CD44, S100A4 and induced genes which alter the actin cytoskeleton (NLF1, NLF2, EPHB4. Examination of the public database of breast cancers revealed tumours exhibiting higher Snail1 expression have an increased risk of disease-recurrence. This was not seen for Snail2, and Zeb1/δEF1 showed a reverse

  20. Behavior of 14C aflatoxin M1 during camembert cheese making.

    Science.gov (United States)

    Fremy, J M; Roiland, J C; Gaymard, A

    1990-01-01

    Camembert cheeses are made from raw milk spiked with aflatoxin M1. Three aflatoxin M1 levels (7.5 micrograms/L, 3 micrograms/L, and 0.3 micrograms/L) are used. In curds 35.6, 47.1, and 57.7% of aflatoxin M1, respectively, are recovered, and in wheys 64.4, 52.9, and 42.3%, respectively, are recovered. During the first 15 days of storage, the aflatoxin M1 content of different cheeses decreases 25, 55, and 75%, respectively. A similar experiment is made with milk contaminated with 14C labeled aflatoxin M1. The same results are obtained, except for the behavior of aflatoxin M1 in cheese; the same 14C activity is recovered during storage for 30 days.

  1. FoxM1 promotes epithelial-mesenchymal transition of hepatocellular carcinoma by targeting Snai1

    OpenAIRE

    Yu, Chun-Peng; Yu, Shui; Shi, Lei; Wang, Song; Li, Zi-Xiang; Wang, Yan-Hua; Sun, Cheng-Jian; Liang, Jun

    2017-01-01

    Forkhead box protein M1 (FoxM1) is aberrantly expressed in several types of human malignancy, and serves an important role in tumor metastasis. Epithelial-mesenchymal transition (EMT) of cancer cells has been associated cancer metastasis; however, the implication of FoxM1 in EMT and its putative roles in the regulation of cancer metastasis remain to be elucidated. In the present study, the expression of FoxM1, Snai1 and E-cadherin in hepatocellular carcinoma (HCC) cell lines with various meta...

  2. Target-specific M1 inputs to infragranular S1 pyramidal neurons

    Science.gov (United States)

    Fanselow, Erika E.; Simons, Daniel J.

    2016-01-01

    The functional role of input from the primary motor cortex (M1) to primary somatosensory cortex (S1) is unclear; one key to understanding this pathway may lie in elucidating the cell-type specific microcircuits that connect S1 and M1. Recently, we discovered that a subset of pyramidal neurons in the infragranular layers of S1 receive especially strong input from M1 (Kinnischtzke AK, Simons DJ, Fanselow EE. Cereb Cortex 24: 2237–2248, 2014), suggesting that M1 may affect specific classes of pyramidal neurons differently. Here, using combined optogenetic and retrograde labeling approaches in the mouse, we examined the strengths of M1 inputs to five classes of infragranular S1 neurons categorized by their projections to particular cortical and subcortical targets. We found that the magnitude of M1 synaptic input to S1 pyramidal neurons varies greatly depending on the projection target of the postsynaptic neuron. Of the populations examined, M1-projecting corticocortical neurons in L6 received the strongest M1 inputs, whereas ventral posterior medial nucleus-projecting corticothalamic neurons, also located in L6, received the weakest. Each population also possessed distinct intrinsic properties. The results suggest that M1 differentially engages specific classes of S1 projection neurons, thereby regulating the motor-related influence S1 exerts over subcortical structures. PMID:27334960

  3. Mitochondrial lineage M1 traces an early human backflow to Africa.

    Science.gov (United States)

    González, Ana M; Larruga, José M; Abu-Amero, Khaled K; Shi, Yufei; Pestano, José; Cabrera, Vicente M

    2007-07-09

    The out of Africa hypothesis has gained generalized consensus. However, many specific questions remain unsettled. To know whether the two M and N macrohaplogroups that colonized Eurasia were already present in Africa before the exit is puzzling. It has been proposed that the east African clade M1 supports a single origin of haplogroup M in Africa. To test the validity of that hypothesis, the phylogeographic analysis of 13 complete mitochondrial DNA (mtDNA) sequences and 261 partial sequences belonging to haplogroup M1 was carried out. The coalescence age of the African haplogroup M1 is younger than those for other M Asiatic clades. In contradiction to the hypothesis of an eastern Africa origin for modern human expansions out of Africa, the most ancestral M1 lineages have been found in Northwest Africa and in the Near East, instead of in East Africa. The M1 geographic distribution and the relative ages of its different subclades clearly correlate with those of haplogroup U6, for which an Eurasian ancestor has been demonstrated. This study provides evidence that M1, or its ancestor, had an Asiatic origin. The earliest M1 expansion into Africa occurred in northwestern instead of eastern areas; this early spread reached the Iberian Peninsula even affecting the Basques. The majority of the M1a lineages found outside and inside Africa had a more recent eastern Africa origin. Both western and eastern M1 lineages participated in the Neolithic colonization of the Sahara. The striking parallelism between subclade ages and geographic distribution of M1 and its North African U6 counterpart strongly reinforces this scenario. Finally, a relevant fraction of M1a lineages present today in the European Continent and nearby islands possibly had a Jewish instead of the commonly proposed Arab/Berber maternal ascendance.

  4. Mitochondrial lineage M1 traces an early human backflow to Africa

    Directory of Open Access Journals (Sweden)

    Pestano José

    2007-07-01

    Full Text Available Abstract Background The out of Africa hypothesis has gained generalized consensus. However, many specific questions remain unsettled. To know whether the two M and N macrohaplogroups that colonized Eurasia were already present in Africa before the exit is puzzling. It has been proposed that the east African clade M1 supports a single origin of haplogroup M in Africa. To test the validity of that hypothesis, the phylogeographic analysis of 13 complete mitochondrial DNA (mtDNA sequences and 261 partial sequences belonging to haplogroup M1 was carried out. Results The coalescence age of the African haplogroup M1 is younger than those for other M Asiatic clades. In contradiction to the hypothesis of an eastern Africa origin for modern human expansions out of Africa, the most ancestral M1 lineages have been found in Northwest Africa and in the Near East, instead of in East Africa. The M1 geographic distribution and the relative ages of its different subclades clearly correlate with those of haplogroup U6, for which an Eurasian ancestor has been demonstrated. Conclusion This study provides evidence that M1, or its ancestor, had an Asiatic origin. The earliest M1 expansion into Africa occurred in northwestern instead of eastern areas; this early spread reached the Iberian Peninsula even affecting the Basques. The majority of the M1a lineages found outside and inside Africa had a more recent eastern Africa origin. Both western and eastern M1 lineages participated in the Neolithic colonization of the Sahara. The striking parallelism between subclade ages and geographic distribution of M1 and its North African U6 counterpart strongly reinforces this scenario. Finally, a relevant fraction of M1a lineages present today in the European Continent and nearby islands possibly had a Jewish instead of the commonly proposed Arab/Berber maternal ascendance.

  5. Properties of M1-M2-Si-Al-O-N glasses (M1 = La or Nd, M2 = Y or Er)

    Energy Technology Data Exchange (ETDEWEB)

    Pomeroy, M.J.; Nestor, E.; Hampshire, S. [Limerick Univ. (Ireland). Materials and Surface Science Inst.; Ramesh, R. [Littelfuse Ireland, Dundalk, Co. Louth (Ireland)

    2002-07-01

    Mixed lanthanide cation oxynitride glasses have been prepared in the M1 - M2 - Si-Al-O-N systems where M1 = La or Nd and M2 = Y or Er. The densities ({rho}), Young's moduli (E), microhardnesses (H{sub v}), glass transition temperatures (T{sub g}), dilatometric softening temperatures (T{sub dil}) and coefficients of thermal expansion (CTE) of 13 glasses were determined. The molar volume values (MV) calculated from density data, E, H{sub v}, T{sub g}, T{sub dil} and CTE values were all found to vary linearly with the effective cation field strength arising from the M1 and M2 modifier cations. Least squares intercept and slope values are presented which correlate each property to effective cation field strength together with error values which arise from glass and specimen preparation and measurement inconsistencies. These linear correlations clearly indicate that the overall glass structure remains the same for each of the thirteen glasses with only the modifier cation(s) having any influence. This influence appears to be a cross-linking effect, the strength of which increases as the effective cation field strength of the M1, M2 modifiers increases. (orig.)

  6. Alterations of M1 and M4 acetylcholine receptors in the genetically dystonic (dtsz) hamster and moderate antidystonic efficacy of M1 and M4 anticholinergics.

    Science.gov (United States)

    Hamann, Melanie; Plank, Jagoda; Richter, Franziska; Bode, Christoph; Smiljanic, Sinisa; Creed, Meaghan; Nobrega, José N; Richter, Angelika

    2017-08-15

    Striatal cholinergic dysfunction has been suggested to play a critical role in the pathophysiology of dystonia. In the dt sz hamster, a phenotypic model of paroxysmal dystonia, M1 antagonists exerted moderate antidystonic efficacy after acute systemic administration. In the present study, we examined the effects of the M4 preferring antagonist tropicamid and whether long-term systemic or acute intrastriatal injections of the M1 preferring antagonist trihexyphenidyl are more effective in mutant hamsters. Furthermore, M1 and M4 receptors were analyzed by autoradiography and immunohistochemistry. Tropicamide retarded the onset of dystonic attacks, as previously observed after acute systemic administration of trihexyphenidyl. Combined systemic administration of trihexyphenidyl (30mg/kg) and tropicamide (15mg/kg) reduced the severity in acute trials and delayed the onset of dystonia during long-term treatment. In contrast, acute striatal microinjections of trihexyphenidyl, tropicamid or the positive allosteric M4 receptor modulator VU0152100 did not exert significant effects. Receptor analyses revealed changes of M1 receptors in the dorsomedial striatum, suggesting that the cholinergic system is involved in abnormal striatal plasticity in dt sz hamsters, but the pharmacological data argue against a crucial role on the phenotype in this animal model. However, antidystonic effects of tropicamide after systemic administration point to a novel therapeutic potential of M4 preferring anticholinergics for the treatment of dystonia. Copyright © 2017 IBRO. Published by Elsevier Ltd. All rights reserved.

  7. Comparison of clinicopathological parameters with FoxM1 expression in renal cell carcinoma

    Directory of Open Access Journals (Sweden)

    Sezen Kocarslan

    2014-01-01

    Conclusion: This study showed that FoxM1 have a progressive oncogenic role in ccRRC. Our results suggested that higher expression of FoxM1 in tumor tissues predicts a locally aggressive behavior and poor outcome of patients with ccRCC, but not in patient with non-ccRCC.

  8. 12 CFR Appendix M1 to Part 226 - Generic Repayment Estimates

    Science.gov (United States)

    2010-01-01

    ... 12 Banks and Banking 3 2010-01-01 2010-01-01 false Generic Repayment Estimates M1 Appendix M1 to Part 226 Banks and Banking FEDERAL RESERVE SYSTEM (CONTINUED) BOARD OF GOVERNORS OF THE FEDERAL RESERVE... rounded down to the nearest whole year if the estimate contains a fractional year less than 0.5, and...

  9. Nanometre-accurate form measurement machine for E-ELT M1 segments

    NARCIS (Netherlands)

    Bos, A.; Henselmans, R.; Rosielle, P.C.J.N.; Steinbuch, M.

    2015-01-01

    To enable important scientific discoveries, ESO has defined a new ground-based telescope: the European Extremely Large Telescope (E-ELT). The baseline design features a telescope with a 39-m-class primary mirror (M1), making it the largest and most powerful telescope in the world. The M1 consists of

  10. 78 FR 13897 - Final Revision and Publication of the 2012 Form M-1, Notice

    Science.gov (United States)

    2013-03-01

    ... DEPARTMENT OF LABOR Employee Benefits Security Administration RIN 1210-AB51 Final Revision and Publication of the 2012 Form M-1, Notice AGENCY: Employee Benefits Security Administration, Department of... revisions to the Form M-1, Report for Multiple Employer Welfare Arrangements (MEWAs) and Certain Entities...

  11. [Appearance of aflatoxin M1 during the manufacture of Camembert cheese].

    Science.gov (United States)

    Frémy, J M; Roiland, J C

    1979-01-01

    Several classic cheese making of camembert are made from raw milk spiked with Aflatoxin M1. Three Aflatoxin levels 7.5 microgram/l, 3 microgram/l are used. In respective curds 35.6, 47.1 and 57.7% of Aflatoxin M1 are recovered and 64.4, 52.9 and 42.3% in respective whey. During the first 15 days of storage the Aflatoxin M1 content of different cheeses decrease respectively 25, 55, 75%. A similar experience is made with a milk contamined in Aflatoxin M1 C14 labelled. Same results are recovered, except about behaviour of Aflatoxin M1 in cheese: a same C14 activity is recovered during storage for 30 days.

  12. Effects of Lactobacillus kefiranofaciens M1 isolated from kefir grains on germ-free mice.

    Science.gov (United States)

    Chen, Yen-Po; Chen, Ming-Ju

    2013-01-01

    Lactobacillus kefiranofaciens M1 is a novel probiotic strain that was isolated from kefir grains. Previously, we have demonstrated the immunoregulatory, anti-allergic, anti-asthmatic and anti-colitis abilities of L. kefiranofaciens M1 in a number of in-vitro and in-vivo experiments. However, whether the effects of L. kefiranofaciens M1 are elicited directly on the host or act by regulating the host's microbiota remains unknown. A number of studies have used germ-free or gnotobiotic animals to investigate the relationship between probiotics and colitis; therefore the aim of this study was to investigate the effects of L. kefiranofaciens M1 on germ-free mice. Such an approach should help in determining the direct effects of L. kefiranofaciens M1 on the host itself. Four-week-old female germ-free mice were inoculated intragastrically with 2×10(8) CFU/mouse L. kefiranofaciens M1 once or at 2-day intervals for 14 days. Bacterial colonization, the Th1/Th2 cytokine profile of the mice's splenocytes and the anti-colitis effect of L. kefiranofaciens M1 were investigated. The strongest response in terms of splenic Th1 cytokine IFN-γ and IL-12 production upon TLR activation was detected in the continuous treatment group when comparing to the single inoculation group and the germ-free control. In addition, continuous inoculation with L. kefiranofaciens M1 was found to ameliorate the symptoms of DSS-induced colitis in germ-free mice. However, L. kefiranofaciens M1 failed to colonize the host. Thus it would seem that L. kefiranofaciens M1 is likely to act directly on the host and not be involved in microbiota regulation.

  13. Effects of Lactobacillus kefiranofaciens M1 isolated from kefir grains on germ-free mice.

    Directory of Open Access Journals (Sweden)

    Yen-Po Chen

    Full Text Available Lactobacillus kefiranofaciens M1 is a novel probiotic strain that was isolated from kefir grains. Previously, we have demonstrated the immunoregulatory, anti-allergic, anti-asthmatic and anti-colitis abilities of L. kefiranofaciens M1 in a number of in-vitro and in-vivo experiments. However, whether the effects of L. kefiranofaciens M1 are elicited directly on the host or act by regulating the host's microbiota remains unknown. A number of studies have used germ-free or gnotobiotic animals to investigate the relationship between probiotics and colitis; therefore the aim of this study was to investigate the effects of L. kefiranofaciens M1 on germ-free mice. Such an approach should help in determining the direct effects of L. kefiranofaciens M1 on the host itself. Four-week-old female germ-free mice were inoculated intragastrically with 2×10(8 CFU/mouse L. kefiranofaciens M1 once or at 2-day intervals for 14 days. Bacterial colonization, the Th1/Th2 cytokine profile of the mice's splenocytes and the anti-colitis effect of L. kefiranofaciens M1 were investigated. The strongest response in terms of splenic Th1 cytokine IFN-γ and IL-12 production upon TLR activation was detected in the continuous treatment group when comparing to the single inoculation group and the germ-free control. In addition, continuous inoculation with L. kefiranofaciens M1 was found to ameliorate the symptoms of DSS-induced colitis in germ-free mice. However, L. kefiranofaciens M1 failed to colonize the host. Thus it would seem that L. kefiranofaciens M1 is likely to act directly on the host and not be involved in microbiota regulation.

  14. Different expression of FoxM1 in human benign and malignant pleural effusion.

    Science.gov (United States)

    Tang, Zhonghao; Li, Hongqing; Zhu, Huili; Bai, Chunxue

    2015-01-01

    The aims of this study were as follows: to analyze the forkhead box M1 (FoxM1) expression in benign and malignant pleural effusion by reverse transcription-polymerase chain reaction assay (RT-PCR); to explore the role of FoxM1 in formation and progress in malignant pleural effusion, and whether there is significant difference in expression level of FoxM1 between benign and malignant pleural effusion; to seek a gene marker diagnostically useful to identify benign and malignant pleural effusion in diagnosis and treatment of pleural effusion; and to collect expression level data of FoxM1 in 23 malignant pleural effusion samples (17 adenocarcinoma samples, four squamous carcinoma samples and two small cell lung carcinoma samples) and 15 benign pleural effusion samples (11 inflammatory pleural effusions, two transudates, two tuberculous pleural effusions) by RT-PCR. Among all 38 samples, average FoxM1 expression level of benign pleural effusions is (235.09 ± 59.99), while malignant pleural effusions (828.77 ± 109.76). Among 23 malignant samples, average FoxM1 expression level is (529.27 ± 75.85) in samples without cytological diagnostic evidence, while (1,218.12 ± 167.21) in samples with cytological diagnostic evidence. Differences of FoxM1 expression level between benign pleural effusions and malignant ones have statistical significance. There is an area of 0.881 under the receiver-operating characteristic curve, which verifies the accuracy of using FoxM1 expression level as diagnostic index to identify benign and malignant pleural effusions. According to our study, diagnostic sensitivity and specificity for FoxM1 expression level at 418.1 were 82.6 and 86.7 %, respectively, while 47.8 and 100 %, respectively, at 768.7. FoxM1 expression level in malignant pleural effusions is significantly higher than in benign ones. This study provides a new approach in clinical diagnosis, with FoxM1 as a specific molecule marker to identify benign and malignant pleural

  15. Oral toxicity evaluation of kefir-isolated Lactobacillus kefiranofaciens M1 in Sprague-Dawley rats.

    Science.gov (United States)

    Owaga, E E; Chen, M J; Chen, W Y; Chen, C W; Hsieh, R H

    2014-08-01

    Lactobacilli kefiranofaciens M1 has shown novel immunomodulation and anti-allergy probiotic attributes in cell and animal models. An acute oral toxicity assessment of L. kefiranofaciens M1 was evaluated in Sprague-Dawley rats. The rats were randomly assigned to four groups (12 rats/sex/group): the low dose group was orally gavaged with L. kefiranofaciens M1 at 3.0×10(8)cfu/kg bw while the medium dose and high dose groups received 9.0×10(9)cfu/kg bw and 1.8×10(10)cfu/kg bw, respectively, for 28days. The control group received phosphate buffer saline. The body weights were measured weekly while blood samples were collected for haematology and serum biochemistry tests. Histopathology of the organs (heart, liver, kidney, adrenal glands, spleen, ovary, testis), and urinalysis were conducted on study termination. The body weight gain of the L. kefiranofaciens M1 and control groups were comparable during the administration period. Overall, L. kefiranofaciens M1 did not induce adverse effects on haematology, serum biochemistry, and urinalysis parameters. Gross and microscopic histopathology of the organs revealed no toxicity effect of L. kefiranofaciens M1. In conclusion, 1.8×10(10)cfu/kg bw of L. kefiranofaciens M1 was considered as the no-observed-adverse-effect-level (NOAEL), which was the highest dose tested in the present study. Copyright © 2014 Elsevier Ltd. All rights reserved.

  16. Techniques used detection and quantification of aflatoxin M1 in milk

    OpenAIRE

    Adriana Frizzarin; Keila Maria Roncato Duarte

    2012-01-01

    Aflatoxin is a group of toxic substances produced by fungi, mainly Aspergillus flavus and Aspergillus parasiticus. It can be developed in agriculture products such as grains or processed food, when environment conditions of humidity and air humidity are favorable. Aflatoxins can be presented as several forms. In Milk, are called M1 and M2, resulting from aflatoxins B1 and B2 metabolism. Aflatoxin M1 (AFM1) is classified as a possible carcinogen to humans, so the occurrence of aflatoxin M1 in ...

  17. Attenuation of cocaine's reinforcing and discriminative stimulus effects via muscarinic M1 acetylcholine receptor stimulation

    DEFF Research Database (Denmark)

    Thomsen, Morgane; Conn, P Jeffrey; Lindsley, Craig

    2010-01-01

    substituted for cocaine and enhanced its discriminative stimulus. Conversely, muscarinic agonists blunted cocaine discrimination and abolished cocaine self-administration with varying effects on food-maintained behavior. Specifically, increasing selectivity for the M(1) subtype (oxotremorine ...'s abuse-related effects, whereas non-M(1)/M(4) receptors probably contribute to undesirable effects of muscarinic stimulation. These data provide the first demonstration of anticocaine effects of systemically applied, M(1) receptor agonists and suggest the possibility of a new approach to pharmacotherapy...

  18. Triaxiality and alternating M1 strengths in f-p-g shell nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Tabor, S L; Johnson, T D; Holcombe, J W; Womble, P C; Doring, J; Nazarewicz, W [Florida State Univ., Tallahassee, FL (United States). Dept. of Physics

    1992-08-01

    The appearance of alternating patterns in B(M1) strengths in f-p-g shell nuclei is surveyed. The M1 alternations in a sequence of N= 41 isotones, in conjunction with particle-rotor model calculations, is shown to provide information about changing {gamma} deformation. In addition to other odd-A nuclei, several odd-odd nuclei are shown to exhibit alternating B(M1) values and signature inversion. alternations have also been reported in a 4 quasiparticle band in {sup 86}Zr, where they have been interpreted in terms of the interacting boson model. (author). 15 refs., 1 tab., 6 figs.

  19. Fine structure of the giant M1 resonance in 90Zr.

    Science.gov (United States)

    Rusev, G; Tsoneva, N; Dönau, F; Frauendorf, S; Schwengner, R; Tonchev, A P; Adekola, A S; Hammond, S L; Kelley, J H; Kwan, E; Lenske, H; Tornow, W; Wagner, A

    2013-01-11

    The M1 excitations in the nuclide 90Zr have been studied in a photon-scattering experiment with monoenergetic and linearly polarized beams from 7 to 11 MeV. More than 40 J(π)=1+ states have been identified from observed ground-state transitions, revealing the fine structure of the giant M1 resonance with a centroid energy of 9 MeV and a sum strength of 4.17(56) μ(N)(2). The result for the total M1 strength and its fragmentation are discussed in the framework of the three-phonon quasiparticle-phonon model.

  20. Towards Revised Step IV MICE Optics in the Absence of M1 SSD

    Energy Technology Data Exchange (ETDEWEB)

    Bayes, R. [Univ. of Glasgow, Scotland (United Kingdom); Berg, J. S. [Brookhaven National Lab. (BNL), Upton, NY (United States); Blackmore, V. [Imperial College, London (United Kingdom); Hunt, C. [Imperial College, London (United Kingdom); Liu, A. [Fermi National Accelerator Lab. (FNAL), Batavia, IL (United States); Pasternak, J. [Imperial College, London (United Kingdom); Rogers, C. T. [Science and Technology Facilities Council (STFC), Oxford (United Kingdom). Rutherford Appleton Lab. (RAL)

    2015-10-01

    During magnet commissioning in September 2015, the leads on coil M1 of the downstream spectrometer solenoid failed. The coil will not be operational for MICE Step IV. Revised optics settings for the Step IV data taking are reviewed.

  1. M1 chimerism following mutagen treatment of seeds in rice and some other cereals

    International Nuclear Information System (INIS)

    Kawai, T.

    1983-01-01

    Articles reporting on M 1 chimerism following treatment of seed with mutagen in cereals were mostly published in the 1960's. Rice is a good material for making such studies because of its relatively large number of seeds per panicle, rather easily identifiable tillering and panicle branching systems and uniform growth after seedling transplanting. The present article summarizes results of studies on M 1 chimerism in rice and some other cereals which may serve as reference information in discussing M 1 chimerism of those plant species showing different development patterns, as dicotyledonous plants, following treatment of seed with mutagen. Studies on M 1 chimerism provide not only knowledge of the sporophyte development but also basic information for developing methods of harvesting M 2 seed which provide the maximum numbers of mutants of different origins in a limited number of M 2 plants. (author)

  2. Techniques used detection and quantification of aflatoxin M1 in milk

    Directory of Open Access Journals (Sweden)

    Adriana Frizzarin

    2012-02-01

    Full Text Available Aflatoxin is a group of toxic substances produced by fungi, mainly Aspergillus flavus and Aspergillus parasiticus. It can be developed in agriculture products such as grains or processed food, when environment conditions of humidity and air humidity are favorable. Aflatoxins can be presented as several forms. In Milk, are called M1 and M2, resulting from aflatoxins B1 and B2 metabolism. Aflatoxin M1 (AFM1 is classified as a possible carcinogen to humans, so the occurrence of aflatoxin M1 in milk of lactating cows is a public health issue, and because of its importance several techniques are used for its detection and quantification. These techniques include the physical-chemical as thin layer chromatography and high performance liquid chromatography and the biological techniques including immunoassays such as RIA and ELISA. This review aimed to present the techniques used to quantify aflatoxins M1 and M2 in milk and dairy products.

  3. Addendum to 'Half coalescence of the m=1, n=1 magnetic island in tokamaks'

    International Nuclear Information System (INIS)

    Bussac, M.N.; Pellat, R.

    1985-01-01

    As an addendum to our previous work concerning the half-coalescence instability of an m=1, n=1 magnetic island in tokamaks, the potential energy is given for an arbitrary shape of the separatrix. (orig.)

  4. Experimental Conditions: SE24_S1_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available rometry with 13C‑Labeling for Chemical Assignment of Sulfur-Containing Metabolites ...SE24_S1_M1_D1 SE24 Combination of Liquid Chromatography-Fourier Transform Ion Cyclotron Resonance-Mass Spect

  5. Inelastic electron scattering, fine structure of M1 giant resonances and Gamow-Teller states

    International Nuclear Information System (INIS)

    Richter, A.

    1983-01-01

    Recent progress in obtaining detailed fine structure distributions of magnetic giant resonances in nuclei using high resolution inelastic electron scattering at low energy is discussed. Specific examples chosen are the medium heavy nuclei 40 42 44 48 Ca in which M1 excitations are due to neutron spin-flip transitions and the N=28 isotones 50 Ti, 52 Cr and 54 Fe where in addition also proton excitations contribute to the measured M1 strength. It is found that the M1 strength is very fragmented and considerably quenched in comparison to predictions of shell model calculations in a model space that includes up to 2p-2h excitations. Finally, the old problem of M1 strength in 208 Pb is revisited and the results of a form factor measurement of a recently discovered low lying Jsup(π)=1 + state by nuclear resonance fluorescence are presented. (Auth.)

  6. The mutual dependence of M1 fertility and M2 mutations in rice

    International Nuclear Information System (INIS)

    Gopinathan Nair, V.

    1982-01-01

    The mutual dependence of M 1 fertility and M 2 mutations in rice was studied after treatment with gamma rays and EMS. The frequency of chlorophyll mutations increased with decrease in seed fertility when M 1 ears were selected at random. However, at the lowest fertility class the mutation frequency was low. This reduction is attributed to the elimination of mutants in the high sterility class. The mutation yield can therefore be significantly enhanced by selecting M 1 ears of low fertility. The segregation ratio of mutants increased as fertility decreased. Mutation spectrum was however not influenced by M 1 fertility. This makes selection for fertility quite ineffective in altering the mutation spectrum. (author)

  7. Towards Revised Step IV MICE Optics in the Absence of M1 SSD

    International Nuclear Information System (INIS)

    Bayes, R.; Berg, J. S.; Blackmore, V.; Hunt, C.; Liu, A.; Pasternak, J.; Rogers, C. T.

    2015-01-01

    During magnet commissioning in September 2015, the leads on coil M1 of the downstream spectrometer solenoid failed. The coil will not be operational for MICE Step IV. Revised optics settings for the Step IV data taking are reviewed.

  8. 76 FR 799 - Publication of Year 2010 Form M-1 With Electronic Filing Option, Notice

    Science.gov (United States)

    2011-01-06

    ... DEPARTMENT OF LABOR Employee Benefits Security Administration Publication of Year 2010 Form M-1 With Electronic Filing Option, Notice AGENCY: Employee Benefits Security Administration, Department of... Employer Welfare Arrangements and Certain Entities Claiming Exception. It is generally identical to the...

  9. Aflatoxin M1 Contamination in Milk and Milk Products in Iran: A Review

    Directory of Open Access Journals (Sweden)

    R. Kazemi Darsanaki

    2014-05-01

    Full Text Available Mycotoxins are secondary metabolites of molds and have adverse effects on humans, animals, and crops. Those can cause illnesses and economic losses. Aflatoxin M1 (AFM1 is one of the mycotoxins produced from the hydroxylated metabolite of aflatoxin B1 (AFB1. It can be found in milk or milk products obtained from livestock that have ingested contaminated feed. In this paper, recent studies were reviewed in aflatoxin M1 contamination in milk and milk products in Iran.

  10. Aflatoxin M1 Contamination in Milk and Milk Products in Iran: A Review

    Directory of Open Access Journals (Sweden)

    R. Kazemi Darsanaki

    2013-11-01

    Full Text Available Mycotoxins are secondary metabolites of molds and have adverse effects on humans, animals, and crops. Those can cause illnesses and economic losses. Aflatoxin M1 (AFM1 is one of the mycotoxins produced from the hydroxylated metabolite of aflatoxin B1 (AFB1. It can be found in milk or milk products obtained from livestock that have ingested contaminated feed. In this paper, recent studies were reviewed in aflatoxin M1 contamination in milk and milk products in Iran.

  11. Emergence and oscillation of cosmic space by joining M1-branes

    International Nuclear Information System (INIS)

    Sepehri, Alireza; Rahaman, Farook; Capozziello, Salvatore; Ali, Ahmed Farag; Pradhan, Anirudh

    2016-01-01

    Recently, it has been proposed by Padmanabhan that the difference between the number of degrees of freedom on the boundary surface and the number of degrees of freedom in a bulk region leads to the expansion of the universe. Now, a natural question arises; how could this model explain the oscillation of the universe between contraction and expansion branches? We try to address this issue in the framework of a BIonic system. In this model, M0-branes join to each other and give rise to a pair of M1-anti-M1-branes. The fields which live on these branes play the roles of massive gravitons that cause the emergence of a wormhole between them and formation of a BIon system. This wormhole dissolves into M1-branes and causes a divergence between the number of degrees of freedom on the boundary surface of M1 and the bulk leading to an expansion of M1-branes. When M1-branes become close to each other, the square energy of their system becomes negative and some tachyonic states emerge. To remove these states, M1-branes become compact, the sign of compacted gravity changes, causing anti-gravity to arise: in this case, branes get away from each other. By articulating M1-BIons, an M3-brane and an anti-M3-brane are created and connected by three wormholes forming an M3-BIon. This new system behaves like the initial system and by closing branes to each other, they become compact and, by getting away from each other, they open. Our universe is located on one of these M3-branes and, by compactifying the M3-brane, it contracts and, by opening it, it expands. (orig.)

  12. Occurrence of B1 Aflatoxin in diet and M1 Aflatoxin in bovine milk

    OpenAIRE

    Adriana Frizzarin; Thiago Pereira Motta; Thamires Martins; Livia Castelani; Heloisa Solda de Azevedo; Cláudia Rodrigues Pozzi

    2012-01-01

    Ensuring food quality is one of the principles of food safety. Food for dairy cattle may be contaminated by fungi of the genus Aspergillus, which produce aflatoxins. The B1 aflatoxin, when ingested by animals, is biotransformed in liver in several other toxic metabolites, including M1 aflatoxin which is excreted in milk. M1 aflatoxin has a carcinogenic effect, which the presence in milk poses a serious risk to public health because milk and dairy products are consumed mainly by children, preg...

  13. Toroidal effects on the non-linearly saturated m = 1 island in tokamaks

    International Nuclear Information System (INIS)

    Avinash, K.; Haas, F.A.; Thyagaraja, A.

    1990-01-01

    This paper investigates the influence of toroidal effects (due to the coupling of various poloidal harmonics) on the non-linear saturation of the m=1 island. Bounds are obtained relating the aspect ratio, the shear at the q=1 surface and the saturated island width. Provided these bounds are satisfied, then we find that the cylindrical m=1 island theory is valid for toroidal geometry. (author)

  14. Emergence and oscillation of cosmic space by joining M1-branes

    Energy Technology Data Exchange (ETDEWEB)

    Sepehri, Alireza [Shahid Bahonar University, Faculty of Physics, Kerman (Iran, Islamic Republic of); Research Institute for Astronomy and Astrophysics of Maragha (RIAAM), Maragha (Iran, Islamic Republic of); Rahaman, Farook [Jadavpur University, Department of Mathematics, Kolkata, West Bengal (India); Capozziello, Salvatore [Universita di Napoli Federico II, Dipartimento di Fisica ' ' E. Pancini' ' , Naples (Italy); Gran Sasso Science Institute (INFN), L' Aquila (Italy); Tomsk State Pedagogical University, Tomsk (Russian Federation); INFN Sezione di Napoli, Naples (Italy); Ali, Ahmed Farag [Benha University, Department of Physics, Faculty of Science, Benha (Egypt); Pradhan, Anirudh [G L A University, Department of Mathematics, Institute of Applied Sciences and Humanities, Mathura, Uttar Pradesh (India)

    2016-05-15

    Recently, it has been proposed by Padmanabhan that the difference between the number of degrees of freedom on the boundary surface and the number of degrees of freedom in a bulk region leads to the expansion of the universe. Now, a natural question arises; how could this model explain the oscillation of the universe between contraction and expansion branches? We try to address this issue in the framework of a BIonic system. In this model, M0-branes join to each other and give rise to a pair of M1-anti-M1-branes. The fields which live on these branes play the roles of massive gravitons that cause the emergence of a wormhole between them and formation of a BIon system. This wormhole dissolves into M1-branes and causes a divergence between the number of degrees of freedom on the boundary surface of M1 and the bulk leading to an expansion of M1-branes. When M1-branes become close to each other, the square energy of their system becomes negative and some tachyonic states emerge. To remove these states, M1-branes become compact, the sign of compacted gravity changes, causing anti-gravity to arise: in this case, branes get away from each other. By articulating M1-BIons, an M3-brane and an anti-M3-brane are created and connected by three wormholes forming an M3-BIon. This new system behaves like the initial system and by closing branes to each other, they become compact and, by getting away from each other, they open. Our universe is located on one of these M3-branes and, by compactifying the M3-brane, it contracts and, by opening it, it expands. (orig.)

  15. Chimerism in M1 plants of Vicia faba, Capsicum annuum and Linum usitatissimum

    International Nuclear Information System (INIS)

    Hermelin, T.; Brunner, H.; Daskalov, S.; Nakai, H.

    1983-01-01

    One important task of our group at IAEA is to develop procedures aiming to improve sampling of M 2 seeds to facilitate the recovery of a maximum number of induced mutations in crop plants. Results from studies on three species are reported in this paper. Seeds have been mutagen treated and the chimeric M 1 plants were progeny tested in M 2 . The position of the M 2 seeds on the M 1 plants has been recorded

  16. The Evaluation of Aflatoxin M1 Level in Collected Raw Milk for Pasteurized Dairy

    Directory of Open Access Journals (Sweden)

    Ehsan Sadeghi

    2013-03-01

    Full Text Available Background: Aflatoxins are fungal toxins that have carcinogenic, cellular mutations and malformation effects. Aflatoxin M1 resists pasteurization, autoclave and the other methods that make foodstuff healthy. This study aims to determine the contents of aflatoxin M1 in raw milk of milk factories in Kermanshah province.Materials and Methods: This research is carried out through the descriptive-cross sectional method. Among the raw milk received by four pasteurized milk factories in Kermanshah, coded by (A, B, C, D labels, six samples, totally 320 samples (80 samples from each factory, were taken within four seasons. The concentration of aflatoxin M1 was examined by Enzyme-Linked Immunosorbent Assay (ELISA. The mean difference was analyzed statistically through t-test using SPSS software. Results: The content of aflatoxin was higher than Codex standard (0.5 µg/l in 295 samples. The total mean was 1.21, which exceeds two times the Codex standard. The highest and lowest contents of aflatoxin M1 were observed in “Factory D” in spring and in “Factory A” in autumn, respectively. There was a significant difference between contamination of aflatoxin M1 and different seasons (p< 0.05.Conclusion: High content of aflatoxin M1 in raw milk is worrying. Measuring the content of aflatoxin M1 is essential to reduce the toxin entering the daily food of animals and the other related factors. The considerable difference of aflatoxin M1 content between Factory D and Factory A can be attributed to the amount of the local milk and the industrial milk received by the factories.

  17. Enhanced M1/M2 macrophage ratio promotes orthodontic root resorption.

    Science.gov (United States)

    He, D; Kou, X; Luo, Q; Yang, R; Liu, D; Wang, X; Song, Y; Cao, H; Zeng, M; Gan, Y; Zhou, Y

    2015-01-01

    Mechanical force-induced orthodontic root resorption is a major clinical challenge in orthodontic treatment. Macrophages play an important role in orthodontic root resorption, but the underlying mechanism remains unclear. In this study, we examined the mechanism by which the ratio of M1 to M2 macrophage polarization affects root resorption during orthodontic tooth movement. Root resorption occurred when nickel-titanium coil springs were applied on the upper first molars of rats for 3 to 14 d. Positively stained odontoclasts or osteoclasts with tartrate-resistant acid phosphatase were found in resorption areas. Meanwhile, M1-like macrophages positive for CD68 and inducible nitric oxide synthase (iNOS) persistently accumulated on the compression side of periodontal tissues. In addition, the expressions of the M1 activator interferon-γ and the M1-associated pro-inflammatory cytokine tumor necrosis factor (TNF)-α were upregulated on the compression side of periodontal tissues. When the coil springs were removed at the 14th day after orthodontic force application, root resorption was partially rescued. The number of CD68(+)CD163(+) M2-like macrophages gradually increased on the compression side of periodontal tissues. The levels of M2 activator interleukin (IL)-4 and the M2-associated anti-inflammatory cytokine IL-10 also increased. Systemic injection of the TNF-α inhibitor etanercept or IL-4 attenuated the severity of root resorption and decreased the ratio of M1 to M2 macrophages. These data imply that the balance between M1 and M2 macrophages affects orthodontic root resorption. Root resorption was aggravated by an enhanced M1/M2 ratio but was partially rescued by a reduced M1/M2 ratio. © International & American Associations for Dental Research 2014.

  18. The effect of proton correlations in the M1 scattering strengths of even calcium isotopes

    International Nuclear Information System (INIS)

    Chaves, L.; Poves, A.

    1986-01-01

    The proton correlations are evaluated in Ca isotopes using the wave functions obtained in an extended shell model calculation in the [1dsub(3/2), 1fsub(7/2), 1fsub(5/2)] valence space. The inclusion of 2p-2h correlations in M1 scattering strengths and magnetic moments improves the agrreement with the experimental data. The M1 strength in 40 Ca is correctly reproduced. (orig.)

  19. FoxM1 is a general target for proteasome inhibitors.

    Directory of Open Access Journals (Sweden)

    Uppoor G Bhat

    2009-08-01

    Full Text Available Proteasome inhibitors are currently in the clinic or in clinical trials, but the mechanism of their anticancer activity is not completely understood. The oncogenic transcription factor FoxM1 is one of the most overexpressed genes in human tumors, while its expression is usually halted in normal non-proliferating cells. Previously, we established that thiazole antibiotics Siomycin A and thiostrepton inhibit FoxM1 and induce apoptosis in human cancer cells. Here, we report that Siomycin A and thiostrepton stabilize the expression of a variety of proteins, such as p21, Mcl-1, p53 and hdm-2 and also act as proteasome inhibitors in vitro. More importantly, we also found that well-known proteasome inhibitors such as MG115, MG132 and bortezomib inhibit FoxM1 transcriptional activity and FoxM1 expression. In addition, overexpression of FoxM1 specifically protects against bortezomib-, but not doxorubicin-induced apoptosis. These data suggest that negative regulation of FoxM1 by proteasome inhibitors is a general feature of these drugs and it may contribute to their anticancer properties.

  20. [Recombinant human gapM1 expressed in Pichia pastoris and its anti-diabetic effect].

    Science.gov (United States)

    Mei, Xiang; Du, Renqian; Li, Xi; Huang, Haiyan; Yu, Min; Tang, Qiqun

    2009-08-01

    Adiponectin is an adipokine predominantly synthesized and secreted by adipocytes in the white adipose tissue, and it can lower the blood glucose level and increase free fatty acid oxidation. In the current study, we developed the globular domain of adiponectin (gapM1) to treat type II diabetes. In both flask and fermentor, we cultivated Pichia pastoris expressing recombinant gapM1 and established the purification procedure by using gel filtration and anion exchange chromatography. To evaluate the biological activity of recombinant gapM1, we used rat type II diabetes model fed high-fat diet in combination with low-dose STZ (Streptozocin) induction. We purified 200 mg gapM1 with purity of 96% from 10 liters of supernatant. The recombinant gapM1 significantly lowered blood glucose (34.2%), serum triglyceride (79.6%) and total cholesterol (62.1%) in type II diabetes induced rat. Therefore, the recombinant human gapM1 is successfully expressed in Pichia pastoris and effectively treated type II diabetes in rat models.

  1. The improvement of M1 polarization in macrophages by glycopeptide derived from Ganoderma lucidum.

    Science.gov (United States)

    Sun, Li-Xin; Lin, Zhi-Bin; Lu, Jie; Li, Wei-Dong; Niu, Yan-Dong; Sun, Yu; Hu, Chen-Yang; Zhang, Guo-Qiang; Duan, Xin-Suo

    2017-06-01

    Ganoderma lucidum (Fr.) Karst (Ganodermataceae) is a medicinal mushroom that has been extensively used in China for centuries to promote longevity and improve vigor without significant adverse effects. There is continuous interest in the bioactive properties of G. lucidum in view of its newly developed popularity in other regions besides Asia, such as Europe. Glycopeptide derived from G. lucidum (Gl-PS) is one of the main effective components isolated from this mushroom. The Gl-PS has been demonstrated pleiotropic with many bioactivities including immunomodulatory and antitumor effects. Macrophages are important cells involved in innate and adaptive immunity. Classically activated macrophages (M1) and alternatively activated macrophages (M2), with their different roles, display distinct cytokine profiles: M1 preferentially produces TNF-α, IL-6, and IL-12; conversely, M2 generates more IL-10 and arginase. Gl-PS might have the potential to promote macrophage M1 polarization by lipopolysaccharide (LPS). In this study, LPS was used to induce the M1 polarization. It was shown that the level of the TNF-α, IL-6, and IL-12 were increased and the IL-10 and arginase I were decreased in the polarized M1 macrophages after application of Gl-PS compared to the control. The results indicated the potential of Gl-PS to promote M1 polarization vs M2, with the health beneficial understanding of the bioactivities of Gl-PS.

  2. AP4M1 is abnormally expressed in oxygen-glucose deprived hippocampal neurons.

    Science.gov (United States)

    Zhang, J; Cheng, X Y; Sheng, G Y

    2014-03-20

    AP4M1 mutations have been suggested to be associated with autosomal recessive cerebral palsy syndrome. But the pathogenic mechanism remains uncertain. The purpose of this study is to investigate whether and how AP4M1 expression is changed in injured neurons. Primary cultured hippocampal neurons were prepared for this experiment. They were subjected to oxygen-glucose deprivation (OGD) leading to apoptosis, mimicking brain ischemia. Neuron-specific enolase (NSE) was labeled immunofluorescently to confirm that the purity of neuron was higher than 90%. Real-time PCR and western blotting were performed to measure the gene expression. AP4M1 was labeled with MAP2 or Tau-1 to observe the distribution. We found that the AP4M1 protein levels immediately after the procedure were similar between the OGD group and the sham group. However, down-regulation was observed 12h after the reperfusion, and became more notable at 24h. The real-time PCR showed similar results, except that the down-regulation of mRNA was able to be detected immediately after the OGD. Immunofluorescent labeling revealed AP4M1 distributed in the dendrites of normal neurons, but it redistributed to the axons after the OGD procedure. In conclusion, AP4M1 is not only down-regulated at both the mRNA and protein levels, but also redistributed from dendrites to axons in oxygen-glucose deprived hippocampal neurons. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  3. Search for weak M 1 transitions in 48Ca with inelastic proton scattering

    Science.gov (United States)

    Mathy, M.; Birkhan, J.; Matsubara, H.; von Neumann-Cosel, P.; Pietralla, N.; Ponomarev, V. Yu.; Richter, A.; Tamii, A.

    2017-05-01

    Background: The quenching of spin-isospin modes in nuclei is an important field of research in nuclear structure. It has an impact on astrophysical reaction rates and on fundamental processes like neutrinoless double-β decay. Gamow-Teller (GT) and spin-flip M 1 strengths are quenched. Concerning the latter, the Jπ=1+ resonance in the doubly magic nucleus 48Ca, dominated by a single transition, serves as a reference case. Purpose: The aim of the present work is to search for weak M 1 transitions in 48Ca with a high-resolution (p ,p') experiment at 295 MeV and forward angles including 0∘ and a comparison with results from a similar study using backward-angle electron scattering at low momentum transfers in order to estimate their contribution to the total B (M 1 ) strength in 48Ca. Methods: The spin-M 1 cross sections of individual peaks in the spectra are deduced with a multipole decomposition analysis (MDA) and converted to reduced spin-M 1 transition strengths by using the unit cross-section method. For a comparison with electron-scattering results, corresponding reduced B (M 1 ) transition strengths are extracted following the approach outlined in Birkhan et al. [Phys. Rev. C 93, 041302(R) (2016), 10.1103/PhysRevC.93.041302]. Results: In total, 30 peaks containing a M 1 contribution are found in the excitation energy region 7-13 MeV. The resulting B (M 1 ) strength distribution compares well to the electron-scattering results considering different factors limiting the sensitivity in both experiments and the enhanced importance of mechanisms breaking the proportionality of nuclear cross sections and electromagnetic matrix elements for weak transitions as studied here. The total strength of 1.14(7) μN2 deduced assuming a nonquenched isoscalar part of the (p ,p') cross sections agrees with the (e ,e') result of 1.21(13) μN2. A bin-wise analysis above 10 MeV provides an upper limit of 1.51(17) μN2. Conclusions: The present results confirm the previous electron

  4. Increased facilitatory connectivity from the pre-SMA to the left dorsal premotor cortex during pseudoword repetition

    DEFF Research Database (Denmark)

    Hartwigsen, Gesa; Saur, Dorothee; Price, Cathy J

    2013-01-01

    Previous studies have demonstrated that the repetition of pseudowords engages a network of premotor areas for articulatory planning and articulation. However, it remains unclear how these premotor areas interact and drive one another during speech production. We used fMRI with dynamic causal mode...

  5. β-adrenergic-stimulated macrophages: Comprehensive localization in the M1–M2 spectrum

    Science.gov (United States)

    Lamkin, Donald M.; Ho, Hsin-Yun; Ong, Tiffany H.; Kawanishi, Carly K.; Stoffers, Victoria L.; Ahlawat, Nivedita; Ma, Jeffrey C.Y.; Arevalo, Jesusa M. G.; Cole, Steve W.; Sloan, Erica K.

    2016-01-01

    β-adrenergic signaling can regulate macrophage involvement in several diseases and often produces anti-inflammatory properties in macrophages, which are similar to M2 properties in a dichotomous M1 vs. M2 macrophage taxonomy. However, it is not clear that β-adrenergic-stimulated macrophages may be classified strictly as M2. In this in vitro study, we utilized recently published criteria and transcriptome-wide bioinformatics methods to map the relative polarity of murine β-adrenergic-stimulated macrophages within a wider M1–M2 spectrum. Results show that β-adrenergic-stimulated macrophages did not fit entirely into any one predefined category of the M1–M2 spectrum but did express genes that are representative of some M2 side categories. Moreover, transcript origin analysis of genome-wide transcriptional profiles located β-adrenergic-stimulated macrophages firmly on the M2 side of the M1–M2 spectrum and found active suppression of M1 side gene transcripts. The signal transduction pathways involved were mapped through blocking experiments and bioinformatics analysis of transcription factor binding motifs. M2-promoting effects were mediated specifically through β2-adrenergic receptors and were associated with CREB, C/EBPβ, and ATF transcription factor pathways but not with established M1–M2 STAT pathways. Thus, β-adrenergic-signaling induces a macrophage transcriptome that locates on the M2 side of the M1–M2 spectrum but likely accomplishes this effect through a signaling pathway that is atypical for M2-spectrum macrophages. PMID:27485040

  6. Learning stage-dependent effect of M1 disruption on value-based motor decisions.

    Science.gov (United States)

    Derosiere, Gerard; Vassiliadis, Pierre; Demaret, Sophie; Zénon, Alexandre; Duque, Julie

    2017-11-15

    The present study aimed at characterizing the impact of M1 disruption on the implementation of implicit value information in motor decisions, at both early stages (during reinforcement learning) and late stages (after consolidation) of action value encoding. Fifty subjects performed, over three consecutive days, a task that required them to select between two finger responses according to the color (instruction) and to the shape (implicit, undisclosed rule) of an imperative signal: considering the implicit rule in addition to the instruction allowed subjects to earn more money. We investigated the functional contribution of M1 to the implementation of the implicit rule in subjects' motor decisions. Continuous theta burst stimulation (cTBS) was applied over M1 either on Day 1 or on Day 3, producing a temporary lesion either during reinforcement learning (cTBS Learning group) or after consolidation of the implicit rule, during decision-making (cTBS Decision group), respectively. Interestingly, disrupting M1 activity on Day 1 improved the reliance on the implicit rule, plausibly because M1 cTBS increased dopamine release in the putamen in an indirect way. This finding corroborates the view that cTBS may affect activity in unstimulated areas, such as the basal ganglia. Notably, this effect was short-lasting; it did not persist overnight, suggesting that the functional integrity of M1 during learning is a prerequisite for the consolidation of implicit value information to occur. Besides, cTBS over M1 did not impact the use of the implicit rule when applied on Day 3, although it did so when applied on Day 2 in a recent study where the reliance on the implicit rule declined following cTBS (Derosiere et al., 2017). Overall, these findings indicate that the human M1 is functionally involved in the consolidation and implementation of implicit value information underlying motor decisions. However, M1 contribution seems to vanish as subjects become more experienced in using

  7. Hyperglycemia induces mixed M1/M2 cytokine profile in primary human monocyte-derived macrophages.

    Science.gov (United States)

    Moganti, Kondaiah; Li, Feng; Schmuttermaier, Christina; Riemann, Sarah; Klüter, Harald; Gratchev, Alexei; Harmsen, Martin C; Kzhyshkowska, Julia

    2017-10-01

    Hyperglycaemia is a key factor in diabetic pathology. Macrophages are essential regulators of inflammation which can be classified into two major vectors of polarisation: classically activated macrophages (M1) and alternatively activated macrophages (M2). Both types of macrophages play a role in diabetes, where M1 and M2-produced cytokines can have detrimental effects in development of diabetes-associated inflammation and diabetic vascular complications. However, the effect of hyperglycaemia on differentiation and programming of primary human macrophages was not systematically studied. We established a unique model to assess the influence of hyperglycaemia on M1 and M2 differentiation based on primary human monocyte-derived macrophages. The effects of hyperglycaemia on the gene expression and secretion of prototype M1 cytokines TNF-alpha and IL-1beta, and prototype M2 cytokines IL-1Ra and CCL18 were quantified by RT-PCR and ELISA. Hyperglycaemia stimulated production of TNF-alpha, IL-1beta and IL-1Ra during macrophage differentiation. The effect of hyperglycaemia on TNF-alpha was acute, while the stimulating effect on IL-1beta and IL-1Ra was constitutive. Expression of CCL18 was supressed in M2 macrophages by hyperglycaemia. However the secreted levels remained to be biologically significant. Our data indicate that hyperglycaemia itself, without additional metabolic factors induces mixed M1/M2 cytokine profile that can support of diabetes-associated inflammation and development of vascular complications. Copyright © 2016 Elsevier GmbH. All rights reserved.

  8. Improved E-ELT subsystem and component specifications, thanks to M1 test facility

    Science.gov (United States)

    Dimmler, M.; Marrero, J.; Leveque, S.; Barriga, Pablo; Sedghi, B.; Kornweibel, N.

    2014-07-01

    During the last 2 years ESO has operated the "M1 Test Facility", a test stand consisting of a representative section of the E-ELT primary mirror equipped with 4 complete prototype segment subunits including sensors, actuators and control system. The purpose of the test facility is twofold: it serves to study and get familiar with component and system aspects like calibration, alignment and handling procedures and suitable control strategies on real hardware long before the primary mirror (hereafter M1) components are commissioned. Secondly, and of major benefit to the project, it offered the possibility to evaluate component and subsystem performance and interface issues in a system context in such detail, that issues could be identified early enough to feed back into the subsystem and component specifications. This considerably reduces risk and cost of the production units and allows refocusing the project team on important issues for the follow-up of the production contracts. Experiences are presented in which areas the results of the M1 Test Facility particularly helped to improve subsystem specifications and areas, where additional tests were adopted independent of the main test facility. Presented are the key experiences of the M1 Test Facility which lead to improved specifications or identified the need for additional testing outside of the M1 Test Facility.

  9. First case report of M1 macrophage polarization in an untreated symptomatic patient with toxoplasmosis.

    Science.gov (United States)

    De Luca, Graziano; Di Lisio, Chiara; Lattanzio, Giuseppe; D'Antuono, Tommaso; Liberatore, Marcella; Aiello, Francesca Bianca

    2018-03-27

    In immunocompetent patients, acute toxoplasmosis is usually asymptomatic. We identified M1 macrophages in a case of symptomatic acute Toxoplasma gondii infection that resolved without treatment. M1 macrophages have been demonstrated in animal models of toxoplasmosis, but not in humans. A 63-year-old woman presented with laterocervical and axillary bilateral lymphadenopathy. Her anamnesis defined an episode of high fever and prolonged asthenia 4 months previously, which suggested an infectious disease. Following laboratory, radiological, and pathological analyses, she was diagnosed with toxoplasmosis. Immunohistochemical analyses were performed on lymph node sections. More than 50% of the macrophages in the lymph node microgranulomas were M1 macrophages, defined by CD68 + /p-Stat1 + staining, and the presence of T helper 1 lymphocytes indicated an immune response known to induce M1 macrophage polarization. Activated endothelial cells were found only in inflamed areas. No therapy was administered before or after diagnosis, and the lymphadenopathy resolved after a follow-up of 5 months. This is the first report to demonstrate the presence of M1 macrophages in human toxoplasmosis. Our findings contribute to the understanding of the pathogenesis of toxoplasmosis, and encourage further studies on the role of macrophage polarization in human toxoplasmosis.

  10. Dopaminergic mesocortical projections to M1: role in motor learning and motor cortex plasticity

    Directory of Open Access Journals (Sweden)

    Jonas Aurel Hosp

    2013-10-01

    Full Text Available Although the architecture of a dopaminergic (DA system within the primary motorcortex (M1 was well characterized anatomically, its functional significance remainedobscure for a long time. Recent studies in rats revealed that the integrity ofdopaminergic fibers in M1 is a prerequisite for successful acquisition of motor skills.This essential contribution of DA for motor learning is plausible as it modulates M1circuitry at multiple levels thereby promoting plastic changes that are required forinformation storage: at the network level, DA increases cortical excitability andenhances the stability of motor maps. At the cellular level, DA induces the expressionof learning related genes via the transcription factor c-fos. At the level of synapses,DA is required for the formation of long-term potentiation (LTP, a mechanism thatlikely is a fingerprint of a motor memory trace within M1. Dopaminergic fibersinnervating M1 originate within the midbrain, precisely the ventral tegmental area(VTA and the medial portion of substantia nigra (SN. Thus, they could be part of themeso-cortico-limibic pathway – a network that provides information about saliencyand motivational value of an external stimulus and is commonly referred as

  11. Nonlinear ω*-stabilization of the m = 1 mode in tokamaks

    International Nuclear Information System (INIS)

    Rogers, B.; Zakharov, L.

    1995-08-01

    Earlier studies of sawtooth oscillations in Tokamak Fusion Test Reactor supershots (Levinton et al, Phys. Rev. Lett. 72, 2895 (1994); Zakharov, et al, Plasma Phys. and Contr. Nucl. Fus. Res., Proc. 15th Int. Conf., Seville 1994, Vienna) have found an apparent contradiction between conventional linear theory and experiment: even in sawtooth-free discharges, the theory typically predicts instability due to a nearly ideal m = 1 mode. Here, the nonlinear evolution of such mode is analyzed using numerical simulations of a two-fluid magnetohydrodynamic (MHD) model. We find the mode saturates nonlinearly at a small amplitude provided the ion and electron drift-frequencies ω* i,e are somewhat above the linear stability threshold of the collisionless m = 1 reconnecting mode. The comparison of the simulation results to m = 1 mode activity in TFTR suggests additional, stabilizing effects outside the present model are also important

  12. Analysis of experimental air-detritiation data using TSOAK-M1

    International Nuclear Information System (INIS)

    Land, R.H.; Maroni, V.A.; Minkoff, M.

    1980-01-01

    A computer code (TSOAK-M1) has been developed which permits the determination of tritium reaction (T 2 to HTO)/adsorption/release and instrument correction parameters from enclosure (building) detritiation test data. The code is based on a simplified model which treats each parameter as a normalized time-independent constant throughout the data-unfolding steps. TSOAK-M1 was used to analyze existing small-cubicle test data with good success, and the resulting normalized parameters were employed to evaluate hypothetical reactor-building detritiation scenarios. It was concluded from the latter evaluation that the complications associated with moisture formation, adsorption, and release, particularly in terms of extended cleanup times, may not be as great as was previously thought. It is recommended that the validity of the TSOAK-M1 model be tested using data from detritiation tests conducted on large experimental enclosures (5 to 10 m 3 ) and, if possible, actual facility buildings

  13. PERUBAHAN KARAKTER KUANTITATIF MUCUNA PRURIENS GENERASI M1 PASCA IRRADIASI SINAR GAMMA CO-60

    Directory of Open Access Journals (Sweden)

    Yustinus Ulung Anggraito

    2015-02-01

    Full Text Available Koro benguk (Mucuna pruriens berpotensi sebagai bahan substitusi kedelai. Keragaman genetik koro benguk termasuk kategori rendah, sehingga perlu ditingkatkan keragaman genetiknya terutama pada faktor-faktor produksi. Tujuan penelitian adalah mendapatkan informasi mutasi mikro pada koro benguk generasi M1 setelah diradiasi dengan sinar gamma dari Cobalt-60. Benih koro benguk diperoleh dari Balai Pengembangan Perbenihan Tanaman Pangan dan Hortikultura (BP2TPH Ngipiksari, Sleman, Yogyakarta. Radiasi sinar gamma dilakukan di PAIR BATAN Pasar Jumat, Jakarta. Dosis radiasi gamma yang digunakan adalah 0; 25 Gy, 50 Gy; 100 Gy; 150 Gy, 200 Gy, dan 250 Gy. Eksperimen dilakukan menggunakan Rancangan Acak Kelompok (RAK. Parameter yang diamati adalah umur berbunga, jumlah polong, jumlah biji, berat 100 biji tanaman generasi M1. Data dianalisis menggunakan Anava, dilanjutkan dengan Uji Beda Nyata Duncan (DMRT. Hasil penelitian menunjukkan bahwa peningkatan dosis radiasi sinar gamma akan memperpanjang hari munculnya bunga dan berat biji, namun menurunkan jumlah polong dan jumlah biji pada tanaman generasi M1.

  14. Application of commercial RIA kit in investigating milk contamination with M1 aflatoxin

    International Nuclear Information System (INIS)

    Fukal, L.

    1988-01-01

    Measured were samples of commercially sold milk produced by two Czech dairies and samples of unprocessed cow's milk from three farms. The determination of aflatoxin M 1 in liquid milk was carried out with a RIA-test-aflatoxin M 1 B 1 kit. The range of the calibration curve of the kit is 0.06 to 2.0 μg/l. In samples of commercially sold milk a higher share of aflatoxin M 1 free samples was found (93%) and 7% samples contained 0.050 to 0.1 μg aflatoxin/l. The dilution effect was manifest in commercially sold milk. On the other hand in 7% samples of raw milk aflatoxin concentration exceeded the limits set by hygiene inspection bodies for consumption by infants. The detected aflatoxin concentrations are compared with data from abroad. (E.S.). 2 tabs., 13 refs

  15. Mission hazard assessment for STARS Mission 1 (M1) in the Marshall Islands area

    Energy Technology Data Exchange (ETDEWEB)

    Outka, D.E.; LaFarge, R.A.

    1993-07-01

    A mission hazard assessment has been performed for the Strategic Target System Mission 1 (known as STARS M1) for hazards due to potential debris impact in the Marshall Islands area. The work was performed at Sandia National Laboratories as a result of discussion with Kwajalein Missile Range (KMR) safety officers. The STARS M1 rocket will be launched from the Kauai Test Facility (KTF), Hawaii, and deliver two payloads to within the viewing range of sensors located on the Kwajalein Atoll. The purpose of this work has been to estimate upper bounds for expected casualty rates and impact probability or the Marshall Islands areas which adjoin the STARS M1 instantaneous impact point (IIP) trace. This report documents the methodology and results of the analysis.

  16. First evidence for spin-flip M1 strength in 40Ar

    International Nuclear Information System (INIS)

    Li, T.C.; Rainovski, G.; Pietralla, N.; Ahn, T.; Costin, A.; Tonchev, A.P.; Ahmed, M.W.; Blackston, M.A.; Parpottas, Y.; Perdue, B.A.; Tornow, W.; Weller, H.R.; Angell, C.; Keeter, K.J.; Li, J.; Mikhailov, S.; Wu, Y.K.; Lisetskiy, A.

    2006-01-01

    The 40 Ar(γ→,γ ' ) photon scattering reaction was used to search for spin-flip M1 strength in 40 Ar. The nearly monochromatic, linearly polarized photon beam of HIγS, in an energy region from 7.7 to 11 MeV, was employed in this study. 28 dipole excitations were observed. The azimuthal intensity asymmetry indicated that all of these states were E1 except for the state at E x =9.757 MeV. Shell-model calculations were used to interpret this state as one fragment of the spin-flip M1 strength in 40 Ar

  17. Design of an E-ELT M1 segment measurement machine with nanometer accuracy

    NARCIS (Netherlands)

    Bos, A.; Henselmans, R.; Rosielle, P.C.J.N.; Steinbuch, M.; te Voert, M.J.A.

    2014-01-01

    The baseline design of the European Extremely Large Telescope features a telescope with a 39-meter-class primary mirror (M1), consisting of 798 hexagonal segments. A measurement machine design is presented based on a non-contact single-point scanning technique, capable of measuring the form error of

  18. Transient analysis of an M/M/1 queue with multiple vacations

    Directory of Open Access Journals (Sweden)

    Kaliappan Kalidass

    2014-05-01

    Full Text Available In this paper, we have obtained explicit expressions for the time dependent probabilities of the M/M/1  queue with server vacations under a multiple vacation scheme. The corresponding steady state probabilities have been obtained. We also obtain the time dependent performance measures of the systems

  19. Study the Effect of Processing of Commercial Kashk Making on Aflatoxin M1 Residue

    Directory of Open Access Journals (Sweden)

    B Hajimohammadi

    2016-03-01

    Full Text Available Introduction: Aflatoxin M1 (AFM1 is a highly toxic compound which is stable during milk processing, and Storage. Hence, it may be found as contaminant in milk and dairy products with hazardous effects for human beings. In this regard, several studies have demonstrated the potential of process to remove Aflatoxin M1 from dairy product. Therefore, the aims of this study were to assess the ability commercial kashk making to reduce Aflatoxin M1 artificially contaminated milk using a natural process of kashk making. Methods: In this study the commercial cheese from cow's milk (skim milk which was contaminated artificially at a level of 0.25 micrograms per liter of aflatoxin M1 was produced at three replications, and the effects of kashk making process on the AFM1 contents were investigated. The HPLC method was used to determine the presence and levels of AFM1. Results: In the commercial kashk production in same concentration between initial milk and commercial kashk caused losses of AFM1 about 91%. These losses were found to be statistically significant (P <0.052 in same concentration between initial milk and commercial kashk. Conclusion: The results of this work demonstrate that the processing of commercial kashk could help to reduce harmful effects of AFM1 humans through consumption of contaminated milk or dairy products.

  20. A Busy period analysis for the state dependent M/M/1/K queue

    NARCIS (Netherlands)

    Al Hanbali, Ahmad; Boxma, Onno

    2010-01-01

    In this paper, we study the transient behavior of a state dependent M/M/1/K queue during the busy period. We derive in closed-form the joint transform of the length of the busy period, the number of customers served during the busy period, and the number of losses during the busy period. For two

  1. Nonlinear calculation of the M=1 internal kink instability in current carrying stellarators

    International Nuclear Information System (INIS)

    Wakatani, M.

    1978-02-01

    Nonlinear properties of the m = 1 internal kink mode are shown in a low β current carrying stellarator. The effects of the external helical magnetic fields are considered through a rotational transform and the magnetic surface is assumed to be circular. Magnetic surfaces inside the iota sub(h) + iota sub(σ) = 1 surface shift and deform non-circularly, while magnetic surfaces outside the iota sub(h) + iota sub(σ) = 1 are not disturbed, where iota sub(h) is a rotational transform due to helical magnetic fields and iota sub(σ) is due to a plasma current. Many higher harmonics are excited after the fundamental mode saturates. When the external helical magnetic fields are lowered, the m = 1 tearing mode similar to that in a low β tokamak grows and magnetic islands appear near the iota sub(h) + iota sub(σ) = 1 surface. For adequate helical magnetic fields, the current carrying stellarator becomes stable against both the m = 1 internal kink mode and the m = 1 tearing mode, without lowering the rotational transform. (auth.)

  2. Effect of Pressure Anisotropy on the m = 1 Small Wavelength Modes in Z-Pinches

    Science.gov (United States)

    Faghihi, M.

    1987-05-01

    A generalization of Freidberg's perpendicular MHD model is used to investigate the effect of pressure anisotropy on the small wavelength internal kink (m = 1) mode instability in a Z-Pinch. A normal mode analysis of perturbed motion of an incompressible, collisionless and cylindrical plasma is performed. The stability criterion is (rΣB2)' = 0.

  3. Homocysteine elicits an M1 phenotype in murine macrophages through an EMMPRIN-mediated pathway.

    Science.gov (United States)

    Winchester, Lee J; Veeranki, Sudhakar; Givvimani, Srikanth; Tyagi, Suresh C

    2015-07-01

    Hyperhomocysteinemia (HHcy) is associated with inflammatory diseases and is known to increase the production of reactive oxygen species (ROS), matrix metalloproteinase (MMP)-9, and inducible nitric oxide synthase, and to decrease endothelial nitric oxide production. However, the impact of HHcy on macrophage phenotype differentiation is not well-established. It has been documented that macrophages have 2 distinct phenotypes: the "classically activated/destructive" (M1), and the "alternatively activated/constructive" (M2) subtypes. We hypothesize that HHcy increases M1 macrophage differentiation through extracellular matrix metalloproteinase inducer (EMMPRIN), a known inducer of matrix metalloproteinases. murine J774A.1 and Raw 264.7 macrophages were treated with 100 and 500 μmol/L Hcy, respectively, for 24 h. Samples were analyzed using Western blotting and immunocytochemistry. Homocysteine treatment increased cluster of differentiation 40 (CD40; M1 marker) in J774A.1 and Raw 264.7 macrophages. MMP-9 was induced in both cell lines. EMMPRIN protein expression was also increased in both cell lines. Blocking EMMPRIN function by pre-treating cells with anti-EMMPRIN antibody, with or without Hcy, resulted in significantly lower expression of CD40 in both cell lines by comparison with the controls. A DCFDA assay demonstrated increased ROS production in both cell lines with Hcy treatment when compared with the controls. Our results suggest that HHcy results in an increase of the M1 macrophage phenotype. This effect seems to be at least partially mediated by EMMPRIN induction.

  4. M1 and E2 transitions in the ground-state configuration of atomic ...

    Indian Academy of Sciences (India)

    have calculated the forbidden transition (M1 and E2) parameters such as transition energies, log- arithmic weighted ... Keywords. Forbidden transitions; transition energies; logarithmic weighted oscillator strengths; .... optimizing the energy function based on the non-relativistic Hamiltonian of an atom,. HNR = N. ∑ j=1. (12∇ ...

  5. Advances in thermal control and performance of the MMT M1 mirror

    Science.gov (United States)

    Gibson, J. D.; Williams, G. G.; Callahan, S.; Comisso, B.; Ortiz, R.; Williams, J. T.

    2010-07-01

    Strategies for thermal control of the 6.5-meter diameter borosilicate honeycomb primary (M1) mirror at the MMT Observatory have included: 1) direct control of ventilation system chiller setpoints by the telescope operator, 2) semiautomated control of chiller setpoints, using a fixed offset from the ambient temperature, and 3) most recently, an automated temperature controller for conditioned air. Details of this automated controller, including the integration of multiple chillers, heat exchangers, and temperature/dew point sensors, are presented here. Constraints and sanity checks for thermal control are also discussed, including: 1) mirror and hardware safety, 2) aluminum coating preservation, and 3) optimization of M1 thermal conditions for science acquisition by minimizing both air-to-glass temperature differences, which cause mirror seeing, and internal glass temperature gradients, which cause wavefront errors. Consideration is given to special operating conditions, such as high dew and frost points. Precise temperature control of conditioned ventilation air as delivered to the M1 mirror cell is also discussed. The performance of the new automated controller is assessed and compared to previous control strategies. Finally, suggestions are made for further refinement of the M1 mirror thermal control system and related algorithms.

  6. TSOAK-M1: an examination of its model and methods

    International Nuclear Information System (INIS)

    Edgell, D.H.

    1983-05-01

    Fusion facilities will contain a sizable inventory of tritium fuel that will be vulnerable to release. Once released, molecular tritium begins converting into tritiated water which is 10000 times more hazardous and tends to adsorb onto surfaces. The rate of conversion and adsorption/desorption must be accurately known to estimate cleanup times and radiation hazards realistically. Argonne National Laboratory developed a computer code, TSOAK-M1, to determine the conversion/ adsorption/desorption parameters and to model cleanups. The Canadian Fusion Fuels Technology Project examined the program for reliability and potential applications. TSOAK-M1 assumes a pseudo second order radiolytic conversion where a first order surface reaction seems more appropriate. This difference in order should be investigated to accurately determine the reaction law. TSOAK-M1 determines the model parameters from experimental data using an optimization routine. However the data used is judged insufficient. More data is needed where the conversion of molecular tritium to tritiated water has a significant effect due to adsorption/desorption. SOAKER, an improved version of the TSOAK-M1 model, which combines first and second order reactions has been implemented in Wang BASIC. Once the reaction law and the parameters have been accurately determined the program could be a useful tool in the study and design of decontamination systems

  7. Analysis of glutathione S-transferase (M1, T1 and P1) gene ...

    African Journals Online (AJOL)

    Glutathione S-transferase enzymes are active in detoxifying a wide number of endogenous and exogenous chemical carcinogens and subsequently, are crucial in protecting the DNA. Several studies show some differences in association of glutathione S-transferase M1, T1 and P1 genetic polymorphisms with the risk of ...

  8. First Observation of the M1 Transition psi -> gamma eta(c)(2S)

    NARCIS (Netherlands)

    Ablikim, M.; Achasov, M. N.; Ambrose, D. J.; An, F. F.; An, Q.; An, Z. H.; Bai, J. Z.; Ban, Y.; Becker, J.; Berger, N.; Bertani, M.; Bian, J. M.; Boger, E.; Bondarenko, O.; Boyko, I.; Briere, R. A.; Bytev, V.; Cai, X.; Calcaterra, A.; Cao, G. F.; Chang, J. F.; Chelkov, G.; Chen, G.; Chen, H. S.; Chen, J. C.; Chen, M. L.; Chen, S. J.; Chen, Y.; Chen, Y. B.; Cheng, H. P.; Chu, Y. P.; Cronin-Hennessy, D.; Dai, H. L.; Dai, J. P.; Dedovich, D.; Deng, Z. Y.; Denig, A.; Denysenko, I.; Destefanis, M.; Ding, W. M.; Ding, Y.; Dong, L. Y.; Dong, M. Y.; Du, S. X.; Fang, J.; Fang, S. S.; Fava, L.; Feldbauer, F.; Feng, C. Q.; Ferroli, R. B.; Fu, C. D.; Fu, J. L.; Gao, Y.; Geng, C.; Goetzen, K.; Gong, W. X.; Gradl, W.; Greco, M.; Gu, M. H.; Gu, Y. T.; Guan, Y. H.; Guo, A. Q.; Guo, L. B.; Guo, Y. P.; Han, Y. L.; Hao, X. Q.; Harris, F. A.; He, K. L.; He, M.; He, Z. Y.; Held, T.; Heng, Y. K.; Hou, Z. L.; Hu, H. M.; Hu, J. F.; Hu, T.; Huang, B.; Huang, G. M.; Huang, J. S.; Huang, X. T.; Huang, Y. P.; Hussain, T.; Ji, C. S.; Ji, Q.; Ji, X. B.; Ji, X. L.; Jia, L. K.; Jiang, L. L.; Jiang, X. S.; Jiao, J. B.; Jiao, Z.; Jin, D. P.; Jin, S.; Jing, F. F.; Kalantar-Nayestanaki, N.; Kavatsyuk, M.; Kuehn, W.; Lai, W.; Lange, J. S.; Leung, J. K. C.; Li, C. H.; Li, Cheng; Li, Cui; Li, D. M.; Li, F.; Li, G.; Li, H. B.; Li, J. C.; Li, K.; Li, Lei; Li, N. B.; Li, Q. J.; Li, S. L.; Li, W. D.; Li, W. G.; Li, X. L.; Li, X. N.; Li, X. Q.; Li, X. R.; Li, Z. B.; Liang, H.; Liang, Y. F.; Liang, Y. T.; Liao, G. R.; Liao, X. T.; Liu, B. J.; Liu, B. J.; Liu, C. L.; Liu, C. X.; Liu, C. Y.; Liu, F. H.; Liu, Fang; Liu, Feng; Liu, H.; Liu, H. B.; Liu, H. H.; Liu, H. M.; Liu, H. W.; Liu, J. P.; Liu, K. Y.; Liu, Kai; Liu, Kun; Liu, P. L.; Liu, S. B.; Liu, X.; Liu, X. H.; Liu, Y.; Liu, Y. B.; Liu, Z. A.; Liu, Zhiqiang; Liu, Zhiqing; Loehner, H.; Lu, G. R.; Lu, H. J.; Lu, J. G.; Lu, Q. W.; Lu, X. R.; Lu, Y. P.; Luo, C. L.; Luo, M. X.; Luo, T.; Luo, X. L.; Lv, M.; Ma, C. L.; Ma, F. C.; Ma, H. L.; Ma, Q. M.; Ma, S.; Ma, T.; Ma, X. Y.; Ma, Y.; Maas, F. E.; Maggiora, M.; Malik, Q. A.; Mao, H.; Mao, Y. J.; Mao, Z. P.; Messchendorp, J. G.; Min, J.; Min, T. J.; Mitchell, R. E.; Mo, X. H.; Morales, C. Morales; Motzko, C.; Muchnoi, N. Yu.; Nefedov, Y.; Nicholson, C.; Nikolaev, I. B.; Ning, Z.; Olsen, S. L.; Ouyang, Q.; Pacetti, S.; Park, J. W.; Pelizaeus, M.; Peng, H. P.; Peters, K.; Ping, J. L.; Ping, R. G.; Poling, R.; Prencipe, E.; Pun, C. S. J.; Qi, M.; Qian, S.; Qiao, C. F.; Qin, X. S.; Qin, Y.; Qin, Z. H.; Qiu, J. F.; Rashid, K. H.; Rong, G.; Ruan, X. D.; Sarantsev, A.; Schaefer, B. D.; Schulze, J.; Shao, M.; Shen, C. P.; Shen, X. Y.; Sheng, H. Y.; Shepherd, M. R.; Song, X. Y.; Spataro, S.; Spruck, B.; Sun, D. H.; Sun, G. X.; Sun, J. F.; Sun, S. S.; Sun, X. D.; Sun, Y. J.; Sun, Y. Z.; Sun, Z. J.; Sun, Z. T.; Tang, C. J.; Tang, X.; Thorndike, E. H.; Tian, H. L.; Toth, D.; Ullrich, M.; Varner, G. S.; Wang, B.; Wang, B. Q.; Wang, K.; Wang, L. L.; Wang, L. S.; Wang, M.; Wang, P.; Wang, P. L.; Wang, Q.; Wang, Q. J.; Wang, S. G.; Wang, X. F.; Wang, X. L.; Wang, Y. D.; Wang, Y. F.; Wang, Y. Q.; Wang, Z.; Wang, Z. G.; Wang, Z. Y.; Wei, D. H.; Weidenkaff, P.; Wen, Q. G.; Wen, S. P.; Werner, M.; Wiedner, U.; Wu, L. H.; Wu, N.; Wu, S. X.; Wu, W.; Wu, Z.; Xia, L. G.; Xiao, Z. J.; Xie, Y. G.; Xiu, Q. L.; Xu, G. F.; Xu, G. M.; Xu, H.; Xu, Q. J.; Xu, X. P.; Xu, Y.; Xu, Z. R.; Xue, F.; Xue, Z.; Yan, L.; Yan, W. B.; Yan, Y. H.; Yang, H. X.; Yang, T.; Yang, Y.; Yang, Y. X.; Ye, H.; Ye, M.; Ye, M. H.; Yu, B. X.; Yu, C. X.; Yu, J. S.; Yu, L.; Yu, S. P.; Yuan, C. Z.; Yuan, W. L.; Yuan, Y.; Zafar, A. A.; Zallo, A.; Zeng, Y.; Zhang, B. X.; Zhang, B. Y.; Zhang, C. C.; Zhang, D. H.; Zhang, H. H.; Zhang, H. Y.; Zhang, J.; Zhang, J. G.; Zhang, J. Q.; Zhang, J. W.; Zhang, J. Y.; Zhang, J. Z.; Zhang, L.; Zhang, S. H.; Zhang, T. R.; Zhang, X. J.; Zhang, X. Y.; Zhang, Y.; Zhang, Y. H.; Zhang, Y. S.; Zhang, Z. P.; Zhang, Z. Y.; Zhao, G.; Zhao, H. S.; Zhao, J. W.; Zhao, K. X.; Zhao, Lei; Zhao, Ling; Zhao, M. G.; Zhao, Q.; Zhao, S. J.; Zhao, T. C.; Zhao, X. H.; Zhao, Y. B.; Zhao, Z. G.; Zhemchugov, A.; Zheng, B.; Zheng, J. P.; Zheng, Y. H.; Zheng, Z. P.; Zhong, B.; Zhong, J.; Zhou, L.; Zhou, X. K.; Zhou, X. R.; Zhu, C.; Zhu, K.; Zhu, K. J.; Zhu, S. H.; Zhu, X. L.; Zhu, X. W.; Zhu, Y. M.; Zhu, Y. S.; Zhu, Z. A.; Zhuang, J.; Zou, B. S.; Zou, J. H.; Zuo, J. X.

    2012-01-01

    Using a sample of 106 x 10(6) psi(3686) events collected with the BESIII detector at the BEPCII storage ring, we have made the first measurement of the M1 transition between the radially excited charmonium S-wave spin-triplet and the radially excited S-wave spin-singlet states: psi(3686) -> gamma

  9. Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity

    International Nuclear Information System (INIS)

    Zhirnov, O.P.; Manykin, A.A.; Rossman, J.S.; Klenk, H.D.

    2016-01-01

    Influenza virus has two major structural modules, an external lipid envelope and an internal ribonucleocapsid containing the genomic RNA in the form of the ribonucleoprotein (RNP) complex, both of which are interlinked by the matrix protein M1. Here we studied M1-RNP cohesion within virus exposed to acidic pH in vitro. The effect of acidification was dependent on the cleavage of the surface glycoprotein HA. Acidic pH caused a loss of intravirion RNP-M1 cohesion and activated RNP polymerase activity in virus with cleaved HA (HA1/2) but not in the uncleaved (HA0) virus. The in vitro acidified HA1/2 virus rapidly lost infectivity whereas the HA0 one retained infectivity, following activation by trypsin, suggesting that premature activation and release of the RNP is detrimental to viral infectivity. Rimantadine, an inhibitor of the M2 ion channel, was found to protect the HA1/2 virus interior against acidic disintegration, confirming that M2-dependent proton translocation is essential for the intravirion RNP release and suggesting that the M2 ion channel is only active in virions with cleaved HA. Acidic treatment of both HA0 and HA1/2 influenza viruses induces formation of spikeless bleb-like protrusion of ~25 nm in diameter on the surface of the virion, though only the HA1/2 virus was permeable to protons and permitted RNP release. It is likely that this bleb corresponds to the M2-enriched and M1-depleted focus arising from pinching off of the virus during the completion of budding. Cooperatively, the data suggest that the influenza virus has an asymmetric structure where the M1-mediated organization of the RNP inside the virion is a prerequisite for infectious entry into target cell. - Highlights: • The influenza A virus has a novel asymmetric internal structure. • The structure is largely maintained by M1-RNP cohesion within the virion. • This asymmetry plays an important role during viral entry, facilitating virus uncoating and the initiation of a productive

  10. Occurrence of B1 Aflatoxin in diet and M1 Aflatoxin in bovine milk

    Directory of Open Access Journals (Sweden)

    Adriana Frizzarin

    2012-12-01

    Full Text Available Ensuring food quality is one of the principles of food safety. Food for dairy cattle may be contaminated by fungi of the genus Aspergillus, which produce aflatoxins. The B1 aflatoxin, when ingested by animals, is biotransformed in liver in several other toxic metabolites, including M1 aflatoxin which is excreted in milk. M1 aflatoxin has a carcinogenic effect, which the presence in milk poses a serious risk to public health because milk and dairy products are consumed mainly by children, pregnant women and elderly. The objective of this study was to detect the presence of B1 aflatoxin in feed supplied to dairy cows and the presence of M1 aflatoxin in milk. Samples were collected from complete diet (corn silage and concentrate from a batch of 15 lactating cows from a dairy farm in the Campinas region. Two samples of diets were collected directly into the troughs in intervals of 24 hours at every 15 days, totalizing a period of 45 days. Milk samples of those cows were collected 24 hours after diet collection, directly from sample valves in the glass jars.. B1 and M1 aflatoxins were detected by the technique of High Performance Liquid Chromatography after extraction and purification on immunoaffinity columns. From the 40 samples of diets evaluated, 40% were contaminated with B1 aflatoxin, and the levels found ranged from 1.93 to 43.78μg/Kg. One sample showed result higher than the maximum recommended for grain and animal feed in Brazil (20μg/Kg. From the 75 milk samples analyzed, the presence of M1 aflatoxin was detected in 13.3% with levels ranging from 0.03 to 0.16μg/L, not exceeding the maximum permitted for marketing in the country of 0.5μg/L, however 80% of contaminated samples had values above the maximum permissible levels of 0.05μg/L, value found among countries with abundant milk production... The presence of aflatoxins highlights the importance of monitoring the production, the storage and the importance of handling food and

  11. Intravirion cohesion of matrix protein M1 with ribonucleocapsid is a prerequisite of influenza virus infectivity

    Energy Technology Data Exchange (ETDEWEB)

    Zhirnov, O.P., E-mail: zhirnov@inbox.ru [D.I. Ivanovsky Institute of Virology, Moscow 123098 (Russian Federation); Manykin, A.A. [D.I. Ivanovsky Institute of Virology, Moscow 123098 (Russian Federation); Rossman, J.S. [School of Biosciences, University of Kent, Canterbury CT27NJ (United Kingdom); Klenk, H.D. [Institute of Virology, Philipps University, Marburg 35037 (Germany)

    2016-05-15

    Influenza virus has two major structural modules, an external lipid envelope and an internal ribonucleocapsid containing the genomic RNA in the form of the ribonucleoprotein (RNP) complex, both of which are interlinked by the matrix protein M1. Here we studied M1-RNP cohesion within virus exposed to acidic pH in vitro. The effect of acidification was dependent on the cleavage of the surface glycoprotein HA. Acidic pH caused a loss of intravirion RNP-M1 cohesion and activated RNP polymerase activity in virus with cleaved HA (HA1/2) but not in the uncleaved (HA0) virus. The in vitro acidified HA1/2 virus rapidly lost infectivity whereas the HA0 one retained infectivity, following activation by trypsin, suggesting that premature activation and release of the RNP is detrimental to viral infectivity. Rimantadine, an inhibitor of the M2 ion channel, was found to protect the HA1/2 virus interior against acidic disintegration, confirming that M2-dependent proton translocation is essential for the intravirion RNP release and suggesting that the M2 ion channel is only active in virions with cleaved HA. Acidic treatment of both HA0 and HA1/2 influenza viruses induces formation of spikeless bleb-like protrusion of ~25 nm in diameter on the surface of the virion, though only the HA1/2 virus was permeable to protons and permitted RNP release. It is likely that this bleb corresponds to the M2-enriched and M1-depleted focus arising from pinching off of the virus during the completion of budding. Cooperatively, the data suggest that the influenza virus has an asymmetric structure where the M1-mediated organization of the RNP inside the virion is a prerequisite for infectious entry into target cell. - Highlights: • The influenza A virus has a novel asymmetric internal structure. • The structure is largely maintained by M1-RNP cohesion within the virion. • This asymmetry plays an important role during viral entry, facilitating virus uncoating and the initiation of a productive

  12. Data on sulforaphane treatment mediated suppression of autoreactive, inflammatory M1 macrophages

    Directory of Open Access Journals (Sweden)

    Sanjima Pal

    2016-06-01

    Full Text Available Any chronic, inflammatory, autoimmune disease (e.g. arthritis associated pathogenesis directs uncontrolled accumulation of both soluble forms of collagens in the synovial fluids and M1 macrophages around inflamed tissues. Despite of few studies demonstrating efficiency of Sulforaphane (SFN in suppressing arthritis associated collagen restricted T cells or fibroblasts, its effects on macrophage polarity and plasticity are less understood. Recently, we reported regulation of phenotypic and functional switching by SFN in induced and spontaneously differentiating human monocytes [1]. Here, flow cytometry, western blot and ELISA derived data demonstrated that SFN inhibited in vitro inflammatory responses developed by soluble human collagens (I–IV induced auto-reactive M1 type monocyte/macrophage model.

  13. CD64: An Attractive Immunotherapeutic Target for M1-type Macrophage Mediated Chronic Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Olusiji A. Akinrinmade

    2017-09-01

    Full Text Available To date, no curative therapy is available for the treatment of most chronic inflammatory diseases such as atopic dermatitis, rheumatoid arthritis, or autoimmune disorders. Current treatments require a lifetime supply for patients to alleviate clinical symptoms and are unable to stop the course of disease. In contrast, a new series of immunotherapeutic agents targeting the Fc γ receptor I (CD64 have emerged and demonstrated significant clinical potential to actually resolving chronic inflammation driven by M1-type dysregulated macrophages. This subpopulation plays a key role in the initiation and maintenance of a series of chronic diseases. The novel recombinant M1-specific immunotherapeutics offer the prospect of highly effective treatment strategies as they have been shown to selectively eliminate the disease-causing macrophage subpopulations. In this review, we provide a detailed summary of the data generated, together with the advantages and the clinical potential of CD64-based targeted therapies for the treatment of chronic inflammatory diseases.

  14. B(M1) values in the band-crossing of shears bands in 197Pb

    Science.gov (United States)

    Krücken, R.; Cooper, J. R.; Beausang, C. W.; Novak, J. R.; Dewald, A.; Klug, T.; Kemper, G.; von Brentano, P.; Carpenter, M.; Wiedenhöver, I.

    We present details of the band crossing mechanism of shears bands using the example of 197Pb. Absolute reduced matrix elements B(M1) were determined by means of a RDM lifetime measurement in one of the shears bands in 197Pb. The experiment was performed using the New Yale Plunger Device (NYPD) in conjunction with the Gammasphere array. Band mixing calculations on the basis of the semi-classical model of the shears mechanism are used to describe the transition matrix elements B(M1) and energies throughout the band-crossing regions. Good agreement with the data was obtained and the detailed composition of the states in the shears band are discussed.

  15. Observation of the M1 giant resonance by resonance averaging in 106Pd

    International Nuclear Information System (INIS)

    Kopecky, J.

    1987-01-01

    An investigation of capture of 2 keV and 24 keV neutrons in a 105 Pd target resulted in resonance-averaged intensities of primary gamma rays with energies between 5.2 and 9.5 MeV. From these intensities the gamma ray strength functions have been evaluated for E1, M1 and E2 radiation and compared with predictions of the giant resonance theory. The inclusion of an energy dependent spreading width for the E1 giant resonance is necessary. The energy distribution of M1 reduced strength is consistent with an interpretation of a broad resonance around 8.8 MeV. E2 data agrees satisfactorily with the giant extrapolation. (orig.)

  16. IKKα Promotes Intestinal Tumorigenesis by Limiting Recruitment of M1-like Polarized Myeloid Cells

    Directory of Open Access Journals (Sweden)

    Serkan I. Göktuna

    2014-06-01

    Full Text Available The recruitment of immune cells into solid tumors is an essential prerequisite of tumor development. Depending on the prevailing polarization profile of these infiltrating leucocytes, tumorigenesis is either promoted or blocked. Here, we identify IκB kinase α (IKKα as a central regulator of a tumoricidal microenvironment during intestinal carcinogenesis. Mice deficient in IKKα kinase activity are largely protected from intestinal tumor development that is dependent on the enhanced recruitment of interferon γ (IFNγ-expressing M1-like myeloid cells. In IKKα mutant mice, M1-like polarization is not controlled in a cell-autonomous manner but, rather, depends on the interplay of both IKKα mutant tumor epithelia and immune cells. Because therapies aiming at the tumor microenvironment rather than directly at the mutated cancer cell may circumvent resistance development, we suggest IKKα as a promising target for colorectal cancer (CRC therapy.

  17. Prototyping the E-ELT M1 local control system communication infrastructure

    Science.gov (United States)

    Argomedo, J.; Kornweibel, N.; Grudzien, T.; Dimmler, M.; Andolfato, L.; Barriga, P.

    2016-08-01

    The primary mirror of the E-ELT is composed of 798 hexagonal segments of about 1.45 meters across. Each segment can be moved in piston and tip-tilt using three position actuators. Inductive edge sensors are used to provide feedback for global reconstruction of the mirror shape. The E-ELT M1 Local Control System will provide a deterministic infrastructure for collecting edge sensor and actuators readings and distribute the new position actuators references while at the same time providing failure detection, isolation and notification, synchronization, monitoring and configuration management. The present paper describes the prototyping activities carried out to verify the feasibility of the E-ELT M1 local control system communication architecture design and assess its performance and potential limitations.

  18. Efficacy of magnetoacustoradiation treatment of experimental M-1, PC-1 tumors

    International Nuclear Information System (INIS)

    Chizh, D.V.; Krutilina, N.I.

    2011-01-01

    The urgency of the struggle against malignant tumors is determined by a stable growth of cancer incidence, high level of disability and morbidity, the cost and difficulty of treatment. The influence of low-frequency ultrasound and alternating magnetic field on transplanted tumors of sarcoma M-1 and alveolar liver cancer PC-1 together with radiation therapy at a SFD of 5 Gy and 20 Gy was investigated in the experiments on animals. It was established that the influence of the above physical factors inhibited sarcoma M-1 and alveolar liver cancer PC-1 growth, prolonged the life and survival of the animals of the investigated groups when compared to the intact controls, which definitely expanded the ideas about the capabilities of ultrasound and magnetic fields in cancer treatment.

  19. Design and optimization of selective azaindole amide M1 positive allosteric modulators.

    Science.gov (United States)

    Davoren, Jennifer E; O'Neil, Steven V; Anderson, Dennis P; Brodney, Michael A; Chenard, Lois; Dlugolenski, Keith; Edgerton, Jeremy R; Green, Michael; Garnsey, Michelle; Grimwood, Sarah; Harris, Anthony R; Kauffman, Gregory W; LaChapelle, Erik; Lazzaro, John T; Lee, Che-Wah; Lotarski, Susan M; Nason, Deane M; Obach, R Scott; Reinhart, Veronica; Salomon-Ferrer, Romelia; Steyn, Stefanus J; Webb, Damien; Yan, Jiangli; Zhang, Lei

    2016-01-15

    Selective activation of the M1 receptor via a positive allosteric modulator (PAM) is a new approach for the treatment of the cognitive impairments associated with schizophrenia and Alzheimer's disease. A novel series of azaindole amides and their key pharmacophore elements are described. The nitrogen of the azaindole core is a key design element as it forms an intramolecular hydrogen bond with the amide N-H thus reinforcing the bioactive conformation predicted by published SAR and our homology model. Representative compound 25 is a potent and selective M1 PAM that has well aligned physicochemical properties, adequate brain penetration and pharmacokinetic (PK) properties, and is active in vivo. These favorable properties indicate that this series possesses suitable qualities for further development and studies. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. The effect of gamma and fast neutron irradiations on M1 seedling growth in soybean

    International Nuclear Information System (INIS)

    Hassan, S.; Mohammad, T.; Khan, S.

    1985-01-01

    Seeds of three varieties of soybean, i.e. Bragg, Hodgson and Lee-74, having a moisture content of 11-13% were irradiated with doses of gamma, 100,200,300,400 and 500 Gray and fast neutron, 5,10,20,25 and 30 Gray, to study the effect on M1 seedling growth. The parameters studied were germination, seedling height and epicotyl length. Growth inhibition was found to increase with increasing radiation doses and the effect on germination was observed only at higher doses. Among early assessable M1 parameters for radio-sensitivity, epicotyl length has proved to be most sensitive, and hence most useful. The Relative Biological Effectiveness (RBE) values for the three varieties differed slightly for epicotyl length and the difference was more pronounced for seedling height. A dose range of 150-300 Gray of gamma rays and 10-15 Gray of fast neutron might prove useful for efficient induced mutation. (authors)

  1. Scissors and unique-parity modes of M1 excitation in deformed nuclei

    International Nuclear Information System (INIS)

    Otsuka, T.

    1989-01-01

    In this paper the possible modes of M1 excitation in deformed even-even nuclei are studied in terms of the particle-number-conserved Nilsson + BCS formalism with the standard parameters. The spurious motion with respect to the rotation is removed. In addition to the Scissors mode, the Unique-Parity Spin and Normal-Parity Spin modes are suggested, although the latter may be fragmented to a large extent. The Scissors mode carries most of the orbital strength, while the others the spin strength. The proton Unique-Parity (i.e. Oh 11/12 ) Spin mode for 164 Dy is obtained just below Ex = 3 MeV with B(M1) ∼ 0.2 μ 2 N ) in the sum rule limit. This is in a good agreement to the recent experimental data

  2. Forbidden Raman scattering processes. I. General considerations and E1--M1 scattering

    International Nuclear Information System (INIS)

    Harney, R.C.

    1979-01-01

    The generalized theory of forbidden Raman scattering processes is developed in terms of the multipole expansion of the electromagnetic interaction Hamiltonian. Using the general expressions, the theory of electric dipole--magnetic dipole (E1--M1) Raman scattering is derived in detail. The 1 S 0 → 3 P 1 E1--M1 Raman scattering cross section in atomic magnesium is calculated for two applicable laser wavelengths using published f-value data. Since resonantly enhanced cross sections larger than 10 -29 cm 2 /sr are predicted it should be possible to experimentally observe this scattering phenomenon. In addition, by measuring the frequency dependence of the cross section near resonance, it may be possible to directly determine the relative magnitudes of the Axp and AxA contributions to the scattering cross section. Finally, possible applications of the effect in atomic and molecular physics are discussed

  3. Theoretical expression of the internal conversion coefficient of a M1 transition between two atomic states

    International Nuclear Information System (INIS)

    Attallah, F.; Chemin, J.F.; Scheurer, J.N.; Karpeshin, F.; Harston, M.

    1997-01-01

    We have established a general relation for the expression of the internal conversion of an M 1 transition a 1s electronic state to an empty ns electronic bound state. Under the hypothesis that the density of the electron level ρ n satisfies the condition ρ n Γ >> 1 (where Γ is the total width of the excited atomic state) a calculation in the first order gives a relation for the internal conversion coefficient.This relation shows that the internal conversion coefficient takes a resonant character when the nuclear energy transition is smaller than the binding energy of the 1s electron. An application of this relation to an M 1 transition in the case of the ion 125 T e with a charge state Q = 45 and an 1s electron binding energy E B 45 = 35.581 KeV gives the value for the internal conversion coefficient R = 5.7

  4. Status and perspectives of the M1 scissors mode in nuclei

    International Nuclear Information System (INIS)

    Richter, A.

    1988-07-01

    The present status of the M1 scissors mode which is now known in deformed nuclei ranging from 46 Ti to 238 U is summarized. Particular emphasis is placed on a discussion of the structure, the excitation energy, the transition strength, the form factor and the spin to orbit ratio in the strength of the mode. Finally it is demonstrated how strongly this mode contributes to the magnetic dipole polarizability of nuclei. (orig.)

  5. Magnetic susceptibility and M1 transitions in /sup 208/Pb. [Sum rules

    Energy Technology Data Exchange (ETDEWEB)

    Traini, M; Lipparini, E; Orlandini, G; Stringari, S [Dipartimento di Matematica e Fisica, Universita di Trento, Italy

    1979-04-16

    M1 transitions in /sup 208/Pb are studied by evaluating energy-weighted and inverse energy-weighted sum-rules. The role of the nuclear interaction is widely discussed. It is shown that the nuclear potential increases the energy-weighted sum rule and lowers the inverse energy-weighted sum rule, with respect to the prediction of the pure shell model. Values of strengths and excitation energies are compared with experimental results and other theoretical calculations.

  6. Measurement of Aflatoxin M1 in Raw and Pasteurized Cow Milk Samples by HPLC

    Directory of Open Access Journals (Sweden)

    afshin Nazari

    2007-10-01

    Full Text Available Nazari A1, Noroozi H2, Movahedi M3, Khaksarian M1 1. Instructor, Department of Physiology, Faculty of Medicine, Lorestan University of Medical Sciences 2. Assistant Professor, Department of Mycology, Faculty of Medicine, Iran University of Medical Sciences 3. Assistant Professor, Department of Genetic Epidemiology, Faculty of Medicine, Lorestan University of Medical Sciences Abstract Background: Aflatoxin M1 is a hydroxylated form of aflatoxin B1 which is produced by Aspergillus flavus. This toxin is produced when cows or other ruminants eat foods contaminated with these mycotoxins and then excrete them in the milk. The toxin is a potent liver and kidney carcinogenetic agent. Materials and methods: Forty two raw cows milk samples from local sources of milk collection and forty samples of commercial pasteurized market milk from Khorramabad, Lorestan, Iran were collected in summer and winter season of 2005. Twenty-one cow milk samples and 20 pasteurized milk samples in each season were analyzed for the presence of aflatoxin M1 (AFM1 by HPLC immunoaffinity columns. Results: Four of 21 raw milk samples in summer showed AFM1 levels between 0.017-0.046 ng/ml and all samples (100% in winter showed the presence of AFM1 levels between 0.003-0.041ng/ ml. AFM1 was detected in 55% of market pasteurized cow milk samples ranging from 0.017 to 0.533 ng/ml in summer and 100% ranging from 0.005-0.0054 ng/ml in winter.,Only one of all milk samples of pasteurized milk in summer had toxin level (0.533 ng/ml more than the maximum permissive limit (0.5 ng/ml. No significant difference was observed among mean contamination level of raw and pasteurized cow milk in two seasons. Key words: Aflatoxin M1, raw milk, pasteurized milk, Khoramabad, HPLC

  7. Presynaptic M1 muscarinic receptor modulates spontaneous release of acetylcholine from rat basal forearm slices

    International Nuclear Information System (INIS)

    Suzuki, T.; Fujimoto, LK.; Oohata, H.; Kawashima, K.

    1988-01-01

    Spontaneous release of (ACh) from rat basal forebrain slices in the presence of cholinesterase inhibitor was directly determined using a specific radioimmunoassay for ACh. The release was calcium dependent. A consistent amount of ACh release was observed throughout the experiment. Atropine (10- 8 to 10- 5 M) and pirenzepine (10- 7 to 10- 5 M) enhanced spontaneous ACh release. These findings indicate the presence of an M 1 muscarenic autoreceptor that modulates spontaneous release of ACh in the rat forebrain

  8. Rac2 controls tumor growth, metastasis and M1-M2 macrophage differentiation in vivo.

    Directory of Open Access Journals (Sweden)

    Shweta Joshi

    Full Text Available Although it is well-established that the macrophage M1 to M2 transition plays a role in tumor progression, the molecular basis for this process remains incompletely understood. Herein, we demonstrate that the small GTPase, Rac2 controls macrophage M1 to M2 differentiation and the metastatic phenotype in vivo. Using a genetic approach, combined with syngeneic and orthotopic tumor models we demonstrate that Rac2-/- mice display a marked defect in tumor growth, angiogenesis and metastasis. Microarray, RT-PCR and metabolomic analysis on bone marrow derived macrophages isolated from the Rac2-/- mice identify an important role for Rac2 in M2 macrophage differentiation. Furthermore, we define a novel molecular mechanism by which signals transmitted from the extracellular matrix via the α4β1 integrin and MCSF receptor lead to the activation of Rac2 and potentially regulate macrophage M2 differentiation. Collectively, our findings demonstrate a macrophage autonomous process by which the Rac2 GTPase is activated downstream of the α4β1 integrin and the MCSF receptor to control tumor growth, metastasis and macrophage differentiation into the M2 phenotype. Finally, using gene expression and metabolomic data from our Rac2-/- model, and information related to M1-M2 macrophage differentiation curated from the literature we executed a systems biologic analysis of hierarchical protein-protein interaction networks in an effort to develop an iterative interactome map which will predict additional mechanisms by which Rac2 may coordinately control macrophage M1 to M2 differentiation and metastasis.

  9. Effect of gamma rays on growth and survival of three mustard varieties in M1 generation

    International Nuclear Information System (INIS)

    Kamala, T.; Rao, R.N.B.

    1982-01-01

    Effects of gamma radiation on germination, survival percentage, seedling height, leaf length and breadth, and growth rate in three mustard varieties were studied in M 1 generation. Seeds were exposed to 15, 30, 45, 60 and 80 Kr doses for the study. Germinations and survival percentages and seedling height showed dose-dependent decrease, while growth rate, leaf length and breadth increased at 60, 45 and 30 Kr and decreased at 80 Kr, though varietal differences were observed. (M.G.B.)

  10. Enhanced Macrophage M1 Polarization and Resistance to Apoptosis Enable Resistance to Plague.

    Science.gov (United States)

    Pachulec, Emilia; Abdelwahed Bagga, Rym Ben; Chevallier, Lucie; O'Donnell, Hope; Guillas, Chloé; Jaubert, Jean; Montagutelli, Xavier; Carniel, Elisabeth; Demeure, Christian E

    2017-09-15

    Susceptibility to infection is in part genetically driven, and C57BL/6 mice resist various pathogens through the proinflammatory response of their M1 macrophages (MPs). However, they are susceptible to plague. It has been reported elsewhere that Mus spretus SEG mice resist plague and develop an immune response characterized by a strong recruitment of MPs. The responses of C57BL/6 and SEG MPs exposed to Yersinia pestis in vitro were examined. SEG MPs exhibit a stronger bactericidal activity with higher nitric oxide production, a more proinflammatory polarized cytokine response, and a higher resistance to Y. pestis-induced apoptosis. This response was not specific to Y. pestis and involved a reduced sensitivity to M2 polarization/signal transducer and activator of transcription 6 activation and inhibition of caspase 8. The enhanced M1 profile was inducible in C57BL/6 MPs in vitro, and when transferred to susceptible C57BL/6 mice, these MPs significantly increased survival of bubonic plague. MPs can develop an enhanced functional profile beyond the prototypic M1, characterized by an even more potent proinflammatory response coordinated with resistance to killing. This programming plays a key role in the plague-resistance phenotype and may be similarly significant in other highly lethal infections, suggesting that orienting the MP response may represent a new therapeutic approach. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  11. Current status of the Thai Research Reactor (TRR-1/M1)

    International Nuclear Information System (INIS)

    Chueinta, Siripone; Julanan, Mongkol; Charncanchee, Decharchai

    2006-01-01

    The first Thai Research Reactor, TRR-1 went critical on 27 October 1962 at the maximum power of 1 MW. It was located at Office of Atoms for Peace (OAP) in Bangkok. Since then, TRR-1 was continuously operated and eventually shut down in 1975. Plate type, high-enriched uranium (HEU) and U 3 O 8 A1 cladding were used as the reactor fuel. Light water was used as moderator and coolant as well. In 1975, because of the problem from fuel supplier and also to supporting the Treaty of Non Proliferation of Nuclear Weapon or NPT, TRR-1 was shut down for modification. The reactor core and control system were disassembled and replaced by TRIGA Mark III. A new core was a hexagonal core shape designed by General Atomics (GA). Afterwards, TRR-1 was officially renamed to the Thai Research Reactor-1/Modification 1 (TRR-1/M1). TRR-1/M1 is a multipurpose swimming pool type reactor with nominal power of 2 MW. The TRR-1/M1 uses uranium enriched at 20% in U-235 (LEU) and ZrH alloy as fuel. Light water is also used as coolant and moderator. At present, the reactor is operating with core No.14. The reactor has been serving for various kinds of utilization namely, radioisotope production, neutron activation analysis, beam experiments and reactor physics experiments. (author)

  12. Surface Termination of M1 Phase and Rational Design of Propane Ammoxidation Catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Guliants, Vadim [Univ. of Cincinnati, OH (United States)

    2015-02-16

    This final report describes major accomplishments in this research project which has demonstrated that the M1 phase is the only crystalline phase required for propane ammoxidation to acrylonitrile and that a surface monolayer terminating the ab planes of the M1 phase is responsible for their activity and selectivity in this reaction. Fundamental studies of the topmost surface chemistry and mechanism of propane ammoxidation over the Mo-V-(Te,Sb)-(Nb,Ta)-O M1 and M2 phases resulted in the development of quantitative understanding of the surface molecular structure – reactivity relationships for this unique catalytic system. These oxides possess unique catalytic properties among mixed metal oxides, because they selectively catalyze three alkane transformation reactions, namely propane ammoxidation to acrylonitrile, propane oxidation to acrylic acid and ethane oxidative dehydrogenation, all of considerable economic significance. Therefore, the larger goal of this research was to expand this catalysis to other alkanes of commercial interest, and more broadly, demonstrate successful approaches to rational design of improved catalysts that can be applied to other selective (amm)oxidation processes.

  13. Assessment of airborne soy-hull allergen (Gly m 1) in the Port of Ancona, Italy.

    Science.gov (United States)

    Antonicelli, L; Ruello, M L; Monsalve, R I; González, R; Fava, G; Bonifazi, F

    2010-10-01

    Epidemic asthma outbreaks are potentially a very high-risk medical situation in seaport towns where large volumes of soybean are loaded and unloaded Airborne allergen assessment plays a pivotal role in evaluating the resulting environmental pollution. The aim of this study was to measure the airborne Gly m 1 allergen level in the seaport of Ancona in order assess the soybean-specific allergenic risk for the city. Allergen and PM10 were evaluated at progressive distances from the port area. Allergen analysis was performed by monoclonal antibody-based immunoassay on the sampled filters. Daily meteorological data were obtained from the local meteorological station. For estimating the assimilative capacity of the atmosphere, an approach based on dispersive ventilation coefficient was tried. The allergen concentrations detected were low (range = 0.4-171 ng/m3). A decreasing gradient of the airborne allergen from the unloading area (22.1 +/- 41.2 ng/m3) to the control area (0.6 +/- 0.7 ng/m3) was detected. The concentration of the airborne Gly m 1 was not coupled with the presence of the soy-carrying ships in the port. A statistically significant relationship between airborne allergen, PM10 and local meteorological parameters quantifies the association with the atmospheric condition. Airborne Gly m 1 is part of the atmospheric dust of Ancona. The low level of this allergen seems consistent with the absence of asthma epidemic outbreak.

  14. Energetic M1 transitions as a probe of nuclear collectivity at high temperatures

    International Nuclear Information System (INIS)

    Baktash, C.

    1987-01-01

    At ORNL, we have recently utilized the Spin Spectrometer setup to investigate the differential effects of increasing spin and excitation energy on nuclear shape and collectivity in 158 Yb. Along the yrast line of this and other N = 88 nuclei, weakly prolate shapes gradually give way to triaxial, and then finally to non-collective oblate shapes as the spin approaches 40 h-bar. However, above the yrast line, large deformation and collectivity once again sets in. This is evidenced by the emergence of a broad quadrupole structure (E/sub γ/ ≅ 1.2 MeV) in the continuum gamma-ray spectra that grows with increasing temperature. The short (sub ps) lifetimes of these transitions attest to the collective nature of these structures. The emergence and growth of the quadrupole structure at high excitation energies is closely correlated with the appearance of energetic (E/sub γ/ ≅ 2.5 MeV), fast M1 transitions which form another broad structure in the continuum spectra. From the centroid of the M1 bump, a quadrupole deformation parameter of 0.35 is inferred. Because of this sensitivity, these energetic M1 transitions provide a unique probe of nuclear shape in the excitation energy range of ≅ 3 to 10 MeV. 6 refs., 2 figs

  15. Input modelling of ASSERT-PV V2R8M1 for RUFIC fuel bundle

    Energy Technology Data Exchange (ETDEWEB)

    Park, Joo Hwan; Suk, Ho Chun

    2001-02-01

    This report describes the input modelling for subchannel analysis of CANFLEX-RU (RUFIC) fuel bundle which has been developed for an advanced fuel bundle of CANDU-6 reactor, using ASSERT-PV V2R8M1 code. Execution file of ASSERT-PV V2R8M1 code was recently transferred from AECL under JRDC agreement between KAERI and AECL. SSERT-PV V2R8M1 which is quite different from COBRA-IV-i code has been developed for thermalhydraulic analysis of CANDU-6 fuel channel by subchannel analysis method and updated so that 43-element CANDU fuel geometry can be applied. Hence, ASSERT code can be applied to the subchannel analysis of RUFIC fuel bundle. The present report was prepared for ASSERT input modelling of RUFIC fuel bundle. Since the ASSERT results highly depend on user's input modelling, the calculation results may be quite different among the user's input models. The objective of the present report is the preparation of detail description of the background information for input data and gives credibility of the calculation results.

  16. Input modelling of ASSERT-PV V2R8M1 for RUFIC fuel bundle

    Energy Technology Data Exchange (ETDEWEB)

    Park, Joo Hwan; Suk, Ho Chun

    2001-02-01

    This report describes the input modelling for subchannel analysis of CANFLEX-RU (RUFIC) fuel bundle which has been developed for an advanced fuel bundle of CANDU-6 reactor, using ASSERT-PV V2R8M1 code. Execution file of ASSERT-PV V2R8M1 code was recently transferred from AECL under JRDC agreement between KAERI and AECL. SSERT-PV V2R8M1 which is quite different from COBRA-IV-i code has been developed for thermalhydraulic analysis of CANDU-6 fuel channel by subchannel analysis method and updated so that 43-element CANDU fuel geometry can be applied. Hence, ASSERT code can be applied to the subchannel analysis of RUFIC fuel bundle. The present report was prepared for ASSERT input modelling of RUFIC fuel bundle. Since the ASSERT results highly depend on user's input modelling, the calculation results may be quite different among the user's input models. The objective of the present report is the preparation of detail description of the background information for input data and gives credibility of the calculation results.

  17. Input modelling of ASSERT-PV V2R8M1 for RUFIC fuel bundle

    International Nuclear Information System (INIS)

    Park, Joo Hwan; Suk, Ho Chun

    2001-02-01

    This report describes the input modelling for subchannel analysis of CANFLEX-RU (RUFIC) fuel bundle which has been developed for an advanced fuel bundle of CANDU-6 reactor, using ASSERT-PV V2R8M1 code. Execution file of ASSERT-PV V2R8M1 code was recently transferred from AECL under JRDC agreement between KAERI and AECL. SSERT-PV V2R8M1 which is quite different from COBRA-IV-i code has been developed for thermalhydraulic analysis of CANDU-6 fuel channel by subchannel analysis method and updated so that 43-element CANDU fuel geometry can be applied. Hence, ASSERT code can be applied to the subchannel analysis of RUFIC fuel bundle. The present report was prepared for ASSERT input modelling of RUFIC fuel bundle. Since the ASSERT results highly depend on user's input modelling, the calculation results may be quite different among the user's input models. The objective of the present report is the preparation of detail description of the background information for input data and gives credibility of the calculation results

  18. Comparative genomics of Streptococcus pyogenes M1 isolates differing in virulence and propensity to cause systemic infection in mice

    NARCIS (Netherlands)

    Fiebig, A.; Loof, T.G.; Babbar, A.; Itzeg, A.; Koehorst, J.J.; Schaap, P.J.; Nitsche-Schmitz, D.P.

    2015-01-01

    Streptococcus pyogenes serotype M1 is a frequent cause of severe infections in humans. Some M1 isolates are pathogenic in mice and used in studies on infection pathogenesis. We observed marked differences in murine infections caused by M1 strain SF370, 5448, 5448AP or AP1 which prompted us to

  19. Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

    Directory of Open Access Journals (Sweden)

    Mário Henrique M Barros

    Full Text Available Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a

  20. Macrophage polarisation: an immunohistochemical approach for identifying M1 and M2 macrophages.

    Science.gov (United States)

    Barros, Mário Henrique M; Hauck, Franziska; Dreyer, Johannes H; Kempkes, Bettina; Niedobitek, Gerald

    2013-01-01

    Macrophage polarization is increasingly recognised as an important pathogenetic factor in inflammatory and neoplastic diseases. Proinflammatory M1 macrophages promote T helper (Th) 1 responses and show tumoricidal activity. M2 macrophages contribute to tissue repair and promote Th2 responses. CD68 and CD163 are used to identify macrophages in tissue sections. However, characterisation of polarised macrophages in situ has remained difficult. Macrophage polarisation is regulated by transcription factors, pSTAT1 and RBP-J for M1, and CMAF for M2. We reasoned that double-labelling immunohistochemistry for the detection of macrophage markers together with transcription factors may be suitable to characterise macrophage polarisation in situ. To test this hypothesis, we have studied conditions associated with Th1- and Th2-predominant immune responses: infectious mononucleosis and Crohn's disease for Th1 and allergic nasal polyps, oxyuriasis, wound healing and foreign body granulomas for predominant Th2 response. In all situations, CD163+ cells usually outnumbered CD68+ cells. Moreover, CD163+ cells, usually considered as M2 macrophages, co-expressing pSTAT1 and RBP-J were found in all conditions examined. The numbers of putative M1 macrophages were higher in Th1- than in Th2-associated diseases, while more M2 macrophages were seen in Th2- than in Th1 related disorders. In most Th1-related diseases, the balance of M1 over M2 cells was shifted towards M1 cells, while the reverse was observed for Th2-related conditions. Hierarchical cluster analysis revealed two distinct clusters: cluster I included Th1 diseases together with cases with high numbers of CD163+pSTAT1+, CD68+pSTAT1+, CD163+RBP-J+ and CD68+RBP-J+ macrophages; cluster II comprised Th2 conditions together with cases displaying high numbers of CD163+CMAF+ and CD68+CMAF+ macrophages. These results suggest that the detection of pSTAT1, RBP-J, and CMAF in the context of CD68 or CD163 expression is a suitable tool for

  1. Relationship between pattern of ischemic manifestation and hemodynamics in symptomatic M1 stenosis

    International Nuclear Information System (INIS)

    Tokumitsu, Naoki; Sako, Kazuhiro; Aizawa, Shizuka; Shirai, Wakako

    2002-01-01

    The mechanism through which ischemic manifestations develop in patients with middle cerebral artery (MCA) stenosis is still uncertain. It may cause ischemic symptoms through both embolic and hemodynamic mechanisms. In this study, we compared the findings from cerebral angiograms with single photon emission computed tomography (SPECT) in patients with M1 stenosis to determine the pathogenesis of ischema. At our hospital from 1994 to 2000, 14 patients (12 males and 2 females; mean age, 60.9; range, 31 to 85 years) with angiographically demonstrated symptomatic M1 stenosis were enrolled in this study. In 10, their stenotic lesion was located at the proximal site of the perforating arteries and for the other 4, stenosis was found at the distal site. Nine presented with transient ischemic attack (TIA) and 5 with completed stroke for an initial episode. The discrepancy in regional cerebral blood flow (rCBF) was evaluated in relation to the site and degree of stenosis, type of ischemic presentation, and frequency of ischemic events. There was no significant difference in CBF between the patients with stenosis involving the proximal site and those with distal stenosis; but the cortical CBF decreased significantly in those with severe stenosis compared with moderate stenosis. The cortical CBF of those who had a complete stroke is similar to that of the patients with TIA; but CBF of BGA decreased significantly in those with a complete stroke. The single ischemic event group showed a significant decrease in cortical CBF. On the other hand, the group with multiple ischemic events exhibited normal hemodynamics. We concluded that multiple ischemic events that occurred in M1 stenosis are caused by an embolic mechanism. (author)

  2. Crotoxin stimulates an M1 activation profile in murine macrophages during Leishmania amazonensis infection.

    Science.gov (United States)

    Farias, L H S; Rodrigues, A P D; Coêlho, E C; Santos, M F; Sampaio, S C; Silva, E O

    2017-09-01

    American tegumentary leishmaniasis is caused by different species of Leishmania. This protozoan employs several mechanisms to subvert the microbicidal activity of macrophages and, given the limited efficacy of current therapies, the development of alternative treatments is essential. Animal venoms are known to exhibit a variety of pharmacological activities, including antiparasitic effects. Crotoxin (CTX) is the main component of Crotalus durissus terrificus venom, and it has several biological effects. Nevertheless, there is no report of CTX activity during macrophage - Leishmania interactions. Thus, the main objective of this study was to evaluate whether CTX has a role in macrophage M1 polarization during Leishmania infection murine macrophages, Leishmania amazonensis promastigotes and L. amazonensis-infected macrophages were challenged with CTX. MTT [3-(4,5dimethylthiazol-2-yl)-2,5-diphenyl tetrasodium bromide] toxicity assays were performed on murine macrophages, and no damage was observed in these cells. Promastigotes, however, were affected by treatment with CTX (IC50 = 22·86 µg mL-1) as were intracellular amastigotes. Macrophages treated with CTX also demonstrated increased reactive oxygen species production. After they were infected with Leishmania, macrophages exhibited an increase in nitric oxide production that converged into an M1 activation profile, as suggested by their elevated production of the cytokines interleukin-6 and tumour necrosis factor-α and changes in their morphology. CTX was able to reverse the L. amazonensis-mediated inhibition of macrophage immune responses and is capable of polarizing macrophages to the M1 profile, which is associated with a better prognosis for cutaneous leishmaniasis treatment.

  3. Mice in Bion-M 1 Space Mission: Training and Selection

    Science.gov (United States)

    Andreev-Andrievskiy, Alexander; Popova, Anfisa; Boyle, Richard; Alberts, Jeffrey; Shenkman, Boris; Vinogradova, Olga; Dolgov, Oleg; Anokhin, Konstantin; Tsvirkun, Darya; Soldatov, Pavel; Nemirovskaya, Tatyana; Ilyin, Eugeniy; Sychev, Vladimir

    2014-01-01

    After a 16-year hiatus, Russia has resumed its program of biomedical research in space, with the successful 30-day flight of the Bion-M 1 biosatellite (April 19–May 19, 2013). The principal species for biomedical research in this project was the mouse. This paper presents an overview of the scientific goals, the experimental design and the mouse training/selection program. The aim of mice experiments in the Bion-M 1 project was to elucidate cellular and molecular mechanisms, underlying the adaptation of key physiological systems to long-term exposure in microgravity. The studies with mice combined in vivo measurements, both in flight and post-flight (including continuous blood pressure measurement), with extensive in vitro studies carried out shortly after return of the mice and in the end of recovery study. Male C57/BL6 mice group housed in space habitats were flown aboard the Bion-M 1 biosatellite, or remained on ground in the control experiment that replicated environmental and housing conditions in the spacecraft. Vivarium control groups were used to account for housing effects and possible seasonal differences. Mice training included the co-adaptation in housing groups and mice adaptation to paste food diet. The measures taken to co-adapt aggressive male mice in housing groups and the peculiarities of “space” paste food are described. The training program for mice designated for in vivo studies was broader and included behavioral/functional test battery and continuous behavioral measurements in the home-cage. The results of the preliminary tests were used for the selection of homogenous groups. After the flight, mice were in good condition for biomedical studies and displayed signs of pronounced disadaptation to Earth's gravity. The outcomes of the training program for the mice welfare are discussed. We conclude that our training program was effective and that male mice can be successfully employed in space biomedical research. PMID:25133741

  4. Ethics control of vertebrate animals experiments in biosatellite BION-M1 project

    Science.gov (United States)

    Ilyin, Eugene

    During April 19-May 19, 2013 it was realized 30-days flight of Russian biosatellite Bion-M1. The main goal of this flight was to study effects of microgravity upon behavior and structural-functional state of different physiological systems of vertebrates. The folloving species were accommodated aboard of biosatellite: 45 mice C57bl/6, 8 Mongolian gerbils Meriones unguiculatus, 15 lizards, i.e. geckos Chondrodctylus turneri Gray, and fish Oreochromis mossambicus. The selection and traing of mice for the flight and ground-based control experiments was carried out at the Research Institute of Mitoengineering by Moscow State University. The protocols for animals care and reserch were revised and adopted by Bioethics Commission of above mentioned institute (decision on November 01, 2013, N35). The final version of Bion-M1 Scientific Reseach Program and protocols for separate experiments were discussed and adopted by Biomedical Ethics Commission of Institute of Biomedical Problems (decision on April 4, 2014, N317). The IMBP Commission has a status of Physiological Section of Russian Bioethics Committee by Russian Commision for UNESCO affairs and follows the Russian Bioethical Guidelines for Experiments in Aerospace and Naval Medicine and other national and international rules including COSPAR International Policy and Guidelines for Animal Care and Use in Space-born Research. Because US-scientists were the main partners in mice investigations the decision of IMBP Biomedical Commission related to Bion-M1 project was sended for information to Institutional Animal Care and Use Committee of NASA Ames Research Center. Postflight estimation of mice was done by Russian veterinary with the participation of NASA Chief veterinary.

  5. Aflatoxin M1 level in pasteurized and sterilized milk of Babol city

    Directory of Open Access Journals (Sweden)

    Hashemi S J

    2007-11-01

    Full Text Available Background: Aflatoxins are severe toxic secondary metabolites found in most plant products. When animals consume contaminated feed stuff to Aflatoxin B1 (AFB1, the toxin is metabolized by liver and is excreted as Aflatoxin M1 (AFM1 via milk. Aflatoxins are acute toxic compounds, immunosuppressive, mutagen, tratogen and carcinogen."nMethods: During the winter of 2006, pasteurized and sterilized (ultra high temperature (UHT milk packages were collected from supermarkets in Babol city. 78 pasteurized and 33 sterilized milk, totally 111 samples were tested for AFM1 by competitive Enzyme Linked Immunosorbent Assay (ELISA. Solid phase in plastic micro wells coated whit anti-Aflatoxin M1 antibodies. We added 100 microliter skimmed milk and Aflatoxin M1 standard solutions in each well. In each plate, we appointed seven wells for standards. Plates were incubated at 20-25 centigrade for 45 min. Each well was washed four times by washing buffer 20X concentration. Then 100 micro liter conjugated solution (100X was added to each well, and the plate was incubated at 20-25 centigrade for 15 min. After that, the wells were washed. After adding the substrates to wells, we incubated the plate at 20-25 centigrade in a dark place for 15 min. The reaction was stopped by stop solution. After one hour, light absorption was read at 450 nm by ELISA reader."nResults: AFM1 were detected in 100% of all samples. 100% of samples were above of European community regulations (50ng/l. AFM1 contamination mean levels pasteurized and sterilized milk were 230.5 and 221.66 respectively. Therefore more than four fold levels European community. There is not a significant relationship between AFM1 contamina-tion level and different months of winter applying statistical test."nConclusion: The results showed the need for introducing safety limits for AFM1 levels in child milk under Food Legislative liable of Iran. Aflatoxin M1 contamination is a serious problem for public health

  6. Observation of the m = 1 mode by microwave transmission measurements in the Tore Supra tokamak

    International Nuclear Information System (INIS)

    Giruzzi, G.; Segui, J.L.; Pecquet, A.L.; Gil, C.

    1991-06-01

    Microwave transmission measurements in the Tore Supra tokamak exhibit low-frequency oscillations of the transmitted power, associated to the presence of a saturated m = 1, n = 1 mode, as observed by soft X-ray diagnostics. It is shown that these oscillations are related to refraction effects, and specifically to modulations of the electron density profile due to a rotating magnetic island. An analytical solution of the ray equations in the presence of a rotating density perturbation is found, explaining the frequency spectrum of the oscillations

  7. Effect of pressure anisotropy on the m=1 small wavelength modes in Z-pinches

    Energy Technology Data Exchange (ETDEWEB)

    Faghihi, M. (Royal Inst. of Tech., Stockholm, Sweden. Dept. of Plasma Physics and Fusion Research)

    1987-05-01

    A generalization of Freidberg's perpendicular MHD model is used to investigate the effect of pressure anisotropy on the small wavelength internal kink (m=1) mode instability in a Z-Pinch. A normal mode analysis of perturbed motion of an incompressible, collisionless and cylindrical plasma is performed. The stability criterion is (r{SIGMA}B{sup 2})' {le} 0, where {SIGMA} = 1 - (P{sub parallel} - P{sub perpendicular} {sub to})/B/sup 2/. It cannot be fulfilled without violation of the fire hose stability condition {SIGMA} {ge} 0.

  8. Effects of pressure anisotropy on the M=1 small wavelength modes in Z-pinches

    International Nuclear Information System (INIS)

    Faghihi, M.

    1986-05-01

    A new model is used to investigate the effect of the pressure anisotropy on the internal kink (m=1) mode instability in a Z-pinch. A normal mode analysis of perturbed motion of an incompressible, collision- less and cylindrical plasma is performed. A comparison of the derived stability criterion with that of ideal MHD is made. The conclusion is that the stability criterion (rSigmaB/sp2/) ' 0, where Sigma=1-(P/sb/(parall)-P/sb/(perpend)/ B/sp/2. (author)

  9. Effect of pressure anisotropy on the m=1 small wavelength modes in Z-pinches

    International Nuclear Information System (INIS)

    Faghihi, M.

    1987-01-01

    A generalization of Freidberg's perpendicular MHD model is used to investigate the effect of pressure anisotropy on the small wavelength internal kink (m=1) mode instability in a Z-Pinch. A normal mode analysis of perturbed motion of an incompressible, collisionless and cylindrical plasma is performed. The stability criterion is (rΣB 2 )' ≤ 0, where Σ = 1 - (P parallel - P perpendicular to )/B 2 . It cannot be fulfilled without violation of the fire hose stability condition Σ ≥ 0. (orig.)

  10. Asymmetric Mach-Zehnder Interferometer Based Biosensors for Aflatoxin M1 Detection.

    Science.gov (United States)

    Chalyan, Tatevik; Guider, Romain; Pasquardini, Laura; Zanetti, Manuela; Falke, Floris; Schreuder, Erik; Heideman, Rene G; Pederzolli, Cecilia; Pavesi, Lorenzo

    2016-01-06

    In this work, we present a study of Aflatoxin M1 detection by photonic biosensors based on Si₃N₄ Asymmetric Mach-Zehnder Interferometer (aMZI) functionalized with antibodies fragments (Fab'). We measured a best volumetric sensitivity of 10⁴ rad/RIU, leading to a Limit of Detection below 5 × 10(-7) RIU. On sensors functionalized with Fab', we performed specific and non-specific sensing measurements at various toxin concentrations. Reproducibility of the measurements and re-usability of the sensor were also investigated.

  11. The M/M/1 queue with inventory, lost sale and general lead times

    DEFF Research Database (Denmark)

    Saffari, Mohammad; Asmussen, Søren; Haji, Rasoul

    We consider an M/M/1 queueing system with inventory under the (r,Q) policy and with lost sales, in which demands occur according to a Poisson process and service times are exponentially distributed. All arriving customers during stockout are lost. We derive the stationary distributions of the joint...... queue length (number of customers in the system) and on-hand inventory when lead times are random variables and can take various distributions. The derived stationary distributions are used to formulate long-run average performance measures and cost functions in some numerical examples....

  12. Nuclear critical opalescence and the M1 form factors of 12C and 13C

    International Nuclear Information System (INIS)

    Delorme, J.; Figureau, A.; Guichon, P.

    1981-01-01

    It is shown that core polarization by the nuclear pion field has opposite effects on the M1 form factors of 12 C(15.11 MeV) and 13 C(g.s.). New data on 13 C are found to agree with this prediction and a common interpretation of the experiments is shown to be possible for the two nuclei in terms of critical opalescence. Discrimination from alternative explanations of the observed anomalies should await further experiments, especially photopion reactions. (orig.)

  13. Contamination levels of aflatoxin M1 in bulk raw milk of Chaloos and Ramsar

    Directory of Open Access Journals (Sweden)

    A.R Barami

    2012-02-01

    Full Text Available Aflatoxin M1 (AFM1 appears in milk as a direct result of the ingestion of feed contaminated with aflatoxin B1 by cattle. This study was conducted to investigate the contamination rate of raw milk whit aflatoxin M1 in Chaloos and Ramsar raw milk collection centers. Two hundred bulk raw milk samples were collected during winter (January and February and summer (June and July seasons. The milk samples were analyzed by ELISA method for the presence of AFM1. During the winter, AFM1 was detected in 100% and 59/79% of the bulk raw milk samples in Ramsar and Chaloos, respectively; however, during summer 83/52% and 50/1 of the samples was found as positive in Ramsar and Chaloos, respectively. Furthermore, 45% of Ramsar and 30% of Chaloos bulk milk samples showed higher contamination level of AFM1 than maximum tolerance limit (50 ng/l accepted by National Standard as well as European Union. Although, the difference between the contamination rate in samples obtained during summer and winter seasons was not statistically significantly, (p

  14. Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase.

    Science.gov (United States)

    McGowan, Sheena; Porter, Corrine J; Lowther, Jonathan; Stack, Colin M; Golding, Sarah J; Skinner-Adams, Tina S; Trenholme, Katharine R; Teuscher, Franka; Donnelly, Sheila M; Grembecka, Jolanta; Mucha, Artur; Kafarski, Pawel; Degori, Ross; Buckle, Ashley M; Gardiner, Donald L; Whisstock, James C; Dalton, John P

    2009-02-24

    Plasmodium falciparum parasites are responsible for the major global disease malaria, which results in >2 million deaths each year. With the rise of drug-resistant malarial parasites, novel drug targets and lead compounds are urgently required for the development of new therapeutic strategies. Here, we address this important problem by targeting the malarial neutral aminopeptidases that are involved in the terminal stages of hemoglobin digestion and essential for the provision of amino acids used for parasite growth and development within the erythrocyte. We characterize the structure and substrate specificity of one such aminopeptidase, PfA-M1, a validated drug target. The X-ray crystal structure of PfA-M1 alone and in complex with the generic inhibitor, bestatin, and a phosphinate dipeptide analogue with potent in vitro and in vivo antimalarial activity, hPheP[CH(2)]Phe, reveals features within the protease active site that are critical to its function as an aminopeptidase and can be exploited for drug development. These results set the groundwork for the development of antimalarial therapeutics that target the neutral aminopeptidases of the parasite.

  15. Process economics and safety considerations for the oxidative dehydrogenation of ethane using the M1 catalyst

    Energy Technology Data Exchange (ETDEWEB)

    Baroi, Chinmoy; Gaffney, Anne M.; Fushimi, Rebecca

    2017-12-01

    Olefins or unsaturated hydrocarbons play a vital role as feedstock for many industrially significant processes. Ethylene is the simplest olefin and a key raw material for consumer products. Oxidative Dehydrogenation (ODH) is one of the most promising new routes for ethylene production that can offer a significant advantage in energy efficiency over the conventional steam pyrolysis process. This study is focused on the ODH chemistry using the mixed metal oxide MoVTeNbOx catalysts, generally referred to as M1 for the key phase known to be active for dehydrogenation. Using performance results from the patent literature a series of process simulations were conducted to evaluate the effect of feed composition on operating costs, profitability and process safety. The key results of this study indicate that the ODH reaction can be made safer and more profitable without use of an inert diluent and furthermore by replacing O2 with CO2 as an oxidant. Modifications of the M1 catalyst composition in order to adopt these changes are discussed.

  16. E2 and M1 transition strengths in heavy deformed nuclei revisited

    International Nuclear Information System (INIS)

    Draayer, J.P.; Popa, G.; Hirsch, J.G.; Vargas, C.E.

    2003-01-01

    An update on the status of pseudo-SU(3) shell-model calculations in strongly deformed nuclei in the rare earth region is presented. Representative results for energy levels as well as E2 (quadrupole) and M1 (scissors) transitions strengths in 162 Dy (even-even) and 163 Dy (odd-mass) are given. The calculations use realistic single-particle energies and quadrupole-quadrupole and pairing interaction strengths fixed from systematics. The strengths of rotor-like terms included in the Hamiltonian- all small relative to the other terms in the interaction were adjusted to give an overall best fit to the energy spectra. The results present a paradox: for even-even nuclei (integer angular momentum) non-zero pseudo-spin configurations seems to be unimportant while for the odd-mass systems (half-integer angular momentum) pseudo-spin mixing is essential as spin-flip couplings appear to dominate the M1 transition strengths. (Author)

  17. Microscopic description of low-lying M1 excitations in odd-mass actinide nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Tabar, Emre, E-mail: etabar@sakarya.edu.tr [Physics Department, Sakarya University, 54187 Sakarya (Turkey); Biomedical, Magnetic and Semiconductor Materials Research Center (BIMAS-RC), Sakarya University, 54187 Sakarya (Turkey); Yakut, Hakan, E-mail: hyakut@sakarya.edu.tr [Physics Department, Sakarya University, 54187 Sakarya (Turkey); Biomedical, Magnetic and Semiconductor Materials Research Center (BIMAS-RC), Sakarya University, 54187 Sakarya (Turkey); Kuliev, Ali Akbar [Azerbaijan National Academy of Aviation, Baku (Azerbaijan)

    2017-01-15

    A restoration method of a broken symmetry which allows self-consistent determination of the separable effective restoration forces is now adapted to odd-mass nuclei in order to restore violated rotational invariance (RI-) of the Quasiparticle Phonon Nuclear Model (QPNM) Hamiltonian. Because of the self-consistency of the method, these effective forces contain no arbitrary parameters. Within RI-QPNM, the properties of the low-lying magnetic dipole excitations in odd-mass deformed {sup 229–233}Th and {sup 233–239}U nuclei have been investigated for the first time. It has been shown that computed fragmentation of the M1 strengths below 4 MeV in these nuclei is much stronger than that in neighboring doubly even {sup 228–232}Th and {sup 232–238}U nuclei. For {sup 235}U the summed M1 strength in the energy range 1.5–2.8 MeV is in agreement with the relevant experimental data where the missing strength was extracted by means of a fluctuation analysis.

  18. Development of Neutron Imaging System for Neutron Tomography at Thai Research Reactor TRR-1/M1

    Science.gov (United States)

    Wonglee, S.; Khaweerat, S.; Channuie, J.; Picha, R.; Liamsuwan, T.; Ratanatongchai, W.

    2017-09-01

    The neutron imaging is a powerful non-destructive technique to investigate the internal structure and provides the information which is different from the conventional X-ray/Gamma radiography. By reconstruction of the obtained 2-dimentional (2D) images from the taken different angle around the specimen, the tomographic image can be obtained and it can provide the information in more detail. The neutron imaging system at Thai Research Reactor TRR-1/M1 of Thailand Institute of Nuclear Technology (Public Organization) has been developed to conduct the neutron tomography since 2014. The primary goal of this work is to serve the investigation of archeological samples, however, this technique can also be applied to various fields, such as investigation of industrial specimen and others. This research paper presents the performance study of a compact neutron camera manufactured by Neutron Optics such as speed and sensitivity. Furthermore, the 3-dimentional (3D) neutron image was successfully reconstructed at the developed neutron imaging system of TRR-1/M1.

  19. Detection of aflatoxin M1 in raw and commercial pasteurized milk in Urmia, Iran.

    Science.gov (United States)

    Tajik, Hossein; Rohani, Seyed Mehdi Razavi; Moradi, Mehran

    2007-11-15

    During the years 2005 and 2006, samples of raw and of pasteurized milk (72 samples each) were collected randomly from various parts of Urmia city in Iran for the detection of aflatoxin M1. Aflatoxin M1 levels were assessed by Enzyme Linked Immuno Sorbent Assay (ELISA). There was a high incidence of AFM1 (100%), in both raw and pasteurized milk samples. The AFM1 levels in 6.25% of samples were higher than the maximum tolerance limit accepted by European Union (50 ng L(-1)), while the observed mean ofAFM1 was lower than those proposed for European diets. Maximum level ofAFM1 in raw and pasteurized samples were 91.8 and 28.5 ng L(-1), while minimum levels were 4.3 and 5.1 ng L(-1), respectively. The levels ofAFM1 in total samples indicated that feeds for cows in this region were contaminated with AFB1 in such a level that appears to be a serious public health problem at the moment. Therefore, there is a need to limit exposure to aflatoxins by imposing regulatory limits.

  20. Aflatoxin M1 contamination of raw and pasteurized milk produced in Sanandaj, Iran

    Directory of Open Access Journals (Sweden)

    Mafakheri, Sh.

    2010-07-01

    Full Text Available This study was conducted to evaluate and compare the levels of aflatoxin M1 in raw and pasteurized milk samples during different seasons by Enzyme- Linked Immuno Sorbent Assay in Sanandaj, Iran. In 257 (94.49% out of 272 milk samples the presence of aflatoxin M1 was detected in concentrations ranging between 0.007 and 115.930 ng/l. AFM1 level in 12 (4.4% of positive samples were higher than the maximum tolerance limit (50 ng/l accepted by Iran and European Union countries. Statistical evaluations showed that the differences between raw and pasteurized samples were not significant (p<0.05. There was no significant difference between spring and summer but the differences between other seasons were statistically significant. Winter samples with 22.35 ng/l and summer samples with 5.14 ng/l had the highest and lowest concentration, respectively (p<0.05. Since contamination of milk with aflatoxin is a potential risk for human health, milk and milk products should be controlled periodically for Aflatoxin contamination.

  1. Nonlinear dynamics of the m=1 kink-tearing instability in a modified magnetohydrodynamic model

    International Nuclear Information System (INIS)

    Wang, X.; Bhattacharjee, A.

    1995-01-01

    A theory is given for the nonlinear dynamical evolution of the collisionless m=1 kink-tearing instability, including the effects of electron inertia and electron pressure gradient in a generalized Ohm's law. It is demonstrated that electron pressure gradients can cause near-explosive growth in the nonlinear regime of a thin m=1 island. This near-explosive phase is followed by a rapid decay phase as the island width becomes comparable to the radius of the sawtooth region. An island equation is derived for the entire nonlinear evolution of the instability, extending recent work on the subject [X. Wang and A. Bhattacharjee, Phys. Rev. Lett. 70, 1627 (1993)] to include the effects of both electron inertia and electron pressure gradient. Comparisons are made with experimental data from present-day tokamaks. It is suggested that the present model not only accounts for fast sawtooth crashes, but also provides possible explanations for the problems of sudden onset and incomplete reconnection that have been, heretofore, unexplained features of observations. copyright 1995 American Institute of Physics

  2. Structural basis for the inhibition of the essential Plasmodium falciparum M1 neutral aminopeptidase

    Science.gov (United States)

    McGowan, Sheena; Porter, Corrine J.; Lowther, Jonathan; Stack, Colin M.; Golding, Sarah J.; Skinner-Adams, Tina S.; Trenholme, Katharine R.; Teuscher, Franka; Donnelly, Sheila M.; Grembecka, Jolanta; Mucha, Artur; Kafarski, Pawel; DeGori, Ross; Buckle, Ashley M.; Gardiner, Donald L.; Whisstock, James C.; Dalton, John P.

    2009-01-01

    Plasmodium falciparum parasites are responsible for the major global disease malaria, which results in >2 million deaths each year. With the rise of drug-resistant malarial parasites, novel drug targets and lead compounds are urgently required for the development of new therapeutic strategies. Here, we address this important problem by targeting the malarial neutral aminopeptidases that are involved in the terminal stages of hemoglobin digestion and essential for the provision of amino acids used for parasite growth and development within the erythrocyte. We characterize the structure and substrate specificity of one such aminopeptidase, PfA-M1, a validated drug target. The X-ray crystal structure of PfA-M1 alone and in complex with the generic inhibitor, bestatin, and a phosphinate dipeptide analogue with potent in vitro and in vivo antimalarial activity, hPheP[CH2]Phe, reveals features within the protease active site that are critical to its function as an aminopeptidase and can be exploited for drug development. These results set the groundwork for the development of antimalarial therapeutics that target the neutral aminopeptidases of the parasite. PMID:19196988

  3. Meiotic chromosome behaviours in M1 generation of bread wheat irradiated by gamma-rays

    International Nuclear Information System (INIS)

    Watanabe, Y.; Takato, S.

    1982-01-01

    Growing plants of bread wheat (Triticum aestivum L. 2 n=6x=42, AABBDD) were subjected to acute or chronic irradiation by gamma-rays from 60Co and meiotic chromosome behaviours of PMCS in M 1 generation were cytologically compared. Both acute and chronic irradiations produced different types of chromosomal aberrations at the meiotic stages. Among them, translocation type was the most frequent, followed by univalent type. A mixed type, i. e. translocation accompanying one or more univalents was often detected. Even normal type which lacked translocation and univalent included laggards and briclges without exception. Other meiotic abnormalities such as deletion, iso-chromosome and micronuclei were observed frequently in both treatments. Dose dependency of translocation frequency was not recognized in this experiment. In chronic irradiation, different chromosome numbers and meiotic behaviours were found not only among florets of a spike but also among anthers of a floret. A number of plants with aneuploid-like grass types occurred at a high frequency in M 1 , especially with low exposure

  4. Compressional effects in nonneutral plasmas, a shallow water analogy and m=1 instability

    International Nuclear Information System (INIS)

    Finn, J.M.; Del-Castillo-Negrete, D.; Barnes, D.C.

    1999-01-01

    Diocotron instabilities form an important class of ExB shear flow instabilities which occur in nonneutral plasmas. The case of a single-species plasma confined in a cylindrical Penning trap, with an axisymmetric, hollow (nonmonotonic) density profile is studied. According to the standard linear theory, the m=1, k z =0 diocotron mode is always stable. On the other hand, experiments by Driscoll [Phys. Rev. Lett. 64, 645 (1990)] show a robust exponential growth of m=1 diocotron perturbations in hollow density profiles. The apparent contradiction between these experimental results and linear theory has been an outstanding problem in the theory of nonneutral plasmas. A new instability mechanism due to the radial variation of the equilibrium plasma length is proposed in this paper. This mechanism involves the compression of the plasma parallel to the magnetic field and implies the conservation of the line integrated density. The predicted growth rate, frequency, and mode structure are in reasonable agreement with the experiment. The effect of a linear perturbation of the plasma length is also shown to give instability with a comparable growth rate. The conservation of the line integrated density in the plasma is analogous to the conservation of the potential vorticity in the shallow water equations used in geophysical fluid dynamics. In particular, there is an analog of Rossby waves in nonneutral plasmas. copyright 1999 American Institute of Physics

  5. Quadrupole decay strength of the M1 scissors mode of {sup 156}Gd

    Energy Technology Data Exchange (ETDEWEB)

    Beck, T.; Beller, J.; Gayer, U.; Mertes, L.; Pai, H.; Pietralla, N.; Ries, P.; Romig, C.; Werner, V.; Zweidinger, M. [IKP, TU Darmstadt (Germany); Derya, V. [IKP, Universitaet zu Koeln (Germany); Isaak, J.; Loeher, B.; Savran, D. [EMMI, GSI, Darmstadt (Germany); FIAS, Frankfurt (Germany); Scheck, M. [IKP, TU Darmstadt (Germany); School of Engineering, UWS, Paisley (United Kingdom); SUPA, Glasgow (United Kingdom); Tornow, W.; Weller, H.R. [Duke University, Durham (United States)

    2015-07-01

    The isovector low-lying J{sup π}{sub K}=1{sup +}{sub 1} scissors mode of deformed nuclei has been studied extensively in (e,e{sup '}) and (γ,γ{sup '}) experiments over the last 30 years with the main focus on strong M1 transitions to the ground state band. In the framework of the semiclassical two-rotor-model it has its origin in quadrupole deformation. A considerable E2 matrix element between the rotational band of the scissors mode and the ground band is predicted which has not been addressed experimentally. A photon-scattering experiment with linearly-polarized quasi monoenergetic vector (γ)-rays has been performed at the High Intensity vector (γ)-ray Source (HIvector (γ)S) at Duke University, Durham, NC, exploiting the γ{sup 3} setup. We have measured an E2/M1-multipole mixing ratio for the 1{sup +}{sub sc}→2{sup +}{sub 1} transition for the first time. The Alaga rule is applicable and delivers a first estimate of the transition strength B(E2:2{sup +}{sub sc}→0{sup +}{sub 1}). A candidate for a 2{sup +}{sub sc}→2{sup +}{sub 1} transition is discussed.

  6. Current status of muscarinic M1 and M4 receptors as drug targets for neurodegenerative diseases.

    Science.gov (United States)

    Felder, Christian C; Goldsmith, Paul J; Jackson, Kimberley; Sanger, Helen E; Evans, David A; Mogg, Adrian J; Broad, Lisa M

    2018-01-25

    The cholinergic signalling system has been an attractive pathway to seek targets for modulation of arousal, cognition, and attention which are compromised in neurodegenerative and neuropsychiatric diseases. The acetylcholine muscarinic receptor M1 and M4 subtypes which are highly expressed in the central nervous system, in cortex, hippocampus and striatum, key areas of cognitive and neuropsychiatric control, have received particular attention. Historical muscarinic drug development yielded first generation agonists with modest selectivity for these two receptor targets over M2 and M3 receptors, the major peripheral sub-types hypothesised to underlie the dose-limiting clinical side effects. More recent compound screening and medicinal chemistry optimization of orthosteric and allosteric agonists, and positive allosteric modulators binding to sites distinct from the highly homologous acetylcholine binding pocket have yielded a collection of highly selective tool compounds for preclinical validation studies. Several M1 selective ligands have progressed to early clinical development and in time will hopefully lead to useful therapeutics for treating symptoms of Alzheimer's disease and related disorders. Copyright © 2018. Published by Elsevier Ltd.

  7. Cytogenetic effects in bone marrow cells of mice exposed on the biosatellite "BION-M1"

    Science.gov (United States)

    Dorozhkina, Olga; Ivanov, Alexander

    In studies of cytogenetic damage in blood lymphocytes of astronauts, conducted in recent years, have shown an increase in the frequency of chromosomal damage bound, as believe, with influence on an organism of astronauts of space radiation (B.S. Fedorenko, G.P. Snigireva, 2004). However, in recent years published evidence that both acute and chronic stress induce chromosomal aberrations and modified genome sensitivity to mutagens of different nature, including to ionizing radiation (F.I. Ingel et al, 2005 ). This question is especially actual for space biology and medicine due to a number of specific features of space flights, when the interaction of factors more pronounced than in normal terrestrial conditions. In experiment "BION - M1" by anaphase method was determined level of chromosomal aberrations in bone marrow cells of tibia of mice. Flight duration biosatellite "BION - M1" was 30 days in Earth orbit. Euthanasia of experimental animals was carried out at intervals of 15-20 minutes by method of cervical dislocation after 12 hours from the moment of landing satellite. Level of chromosomal aberrations in vivarium-housed control mice was 1,75 ± 0,6% and 1,8 ± 0,45%, while the mitotic index 1,46 ± 0,09% and 1,53 ± 0,05%. Differences are not significant. The maintenance of animals in experiment with the onboard equipment (ground experiment) led to some increase in aberrant mitoses (2,3 ± 0,4%) and to decrease in a mitotic index (1,37 ± 0,02%). In the flight experiment "BION - M1" statistically significant increase of level of chromosomal aberrations (29,7 ± 4,18%) and a decrease in the mitotic index (0,74 ± 0,07%). Since the mouse is a suitable experimental model , also had several ground experiments on research of combined effect of irradiation and other stress factors specific to space flight, with marked tendency to increase the level of aberrant mitoses under the combined action of radiation and stress exposure group housing male mice. Statistically

  8. M1 muscarinic receptor facilitates cognitive function by interplay with AMPA receptor GluA1 subunit.

    Science.gov (United States)

    Zhao, Lan-Xue; Ge, Yan-Hui; Xiong, Cai-Hong; Tang, Ling; Yan, Ying-Hui; Law, Ping-Yee; Qiu, Yu; Chen, Hong-Zhuan

    2018-03-06

    M1 muscarinic acetylcholine receptors (M1 mAChRs) are the most abundant muscarinic receptors in the hippocampus and have been shown to have procognitive effects. AMPA receptors (AMPARs), an important subtype of ionotropic glutamate receptors, are key components in neurocognitive networks. However, the role of AMPARs in procognitive effects of M1 mAChRs and how M1 mAChRs affect the function of AMPARs remain poorly understood. Here, we found that basal expression of GluA1, a subunit of AMPARs, and its phosphorylation at Ser845 were maintained by M1 mAChR activity. Activation of M1 mAChRs promoted membrane insertion of GluA1, especially to postsynaptic densities. Impairment of hippocampus-dependent learning and memory by antagonism of M1 mAChRs paralleled the reduction of GluA1 expression, and improvement of learning and memory by activation of M1 mAChRs was accompanied by the synaptic insertion of GluA1 and its increased phosphorylation at Ser845. Furthermore, abrogation of phosphorylation of Ser845 residue of GluA1 ablated M1 mAChR-mediated improvement of learning and memory. Taken together, these results show a functional correlation of M1 mAChRs and GluA1 and the essential role of GluA1 in M1 mAChR-mediated cognitive improvement.-Zhao, L.-X., Ge, Y.-H., Xiong, C.-H., Tang, L., Yan, Y.-H., Law, P.-Y., Qiu, Y., Chen, H.-Z. M1 muscarinic receptor facilitates cognitive function by interplay with AMPA receptor GluA1 subunit.

  9. Forkhead Box M1 Is Regulated by Heat Shock Factor 1 and Promotes Glioma Cells Survival under Heat Shock Stress*

    Science.gov (United States)

    Dai, Bingbing; Gong, Aihua; Jing, Zhitao; Aldape, Kenneth D.; Kang, Shin-Hyuk; Sawaya, Raymond; Huang, Suyun

    2013-01-01

    The forkhead box M1 (FoxM1) is a key transcription factor regulating multiple aspects of cell biology. Prior studies have shown that FoxM1 is overexpressed in a variety of human tumors, including brain tumor, and plays a critical role in cancer development and progression. In this study we found that FoxM1 was up-regulated by heat shock factor 1 (HSF1) under heat shock stress condition in multiple cell lines. Knockdown of HSF1 with HSF1 siRNA or inhibition of HSF1 with a HSF1 inhibitor abrogated heat shock-induced expression of FoxM1. Genetic deletion of HSF1 in mouse embryo fibroblast cells also abolished heat shock stress-induced FoxM1 expression. Moreover, we showed that HSF1 directly bound to FoxM1 promoter and increased FoxM1 promoter activity. Furthermore, we demonstrated that FoxM1 was required for the G2-M phase progression through regulating Cdc2, Cdc20, and Cdc25B under a mild heat shock stress but enhanced cell survival under lethal heat shock stress condition. Finally, in human glioblastoma specimens, FoxM1 overexpression correlated with elevated HSF1 expression. Our results indicate that FoxM1 is regulated by HSF1 and is critical for HSF1-mediated heat shock response. We demonstrated a novel mechanism of stress resistance controlled by HSF1 and a new HSF-FoxM1 connection that mediates cellular thermotolerance. PMID:23192351

  10. On the GI/M/1 Queue with Vacations and Multiple Service Phases

    Directory of Open Access Journals (Sweden)

    Jianjun Li

    2017-01-01

    Full Text Available This paper considers a GI/M/1 queue with vacations and multiple service phases. Whenever the system becomes empty, the server takes a vacation, causing the system to move to vacation phase 0. If the server returns from a vacation to find no customer waiting, another vacation begins. Otherwise, the system jumps from phase 0 to some service phase i with probability qi,  i=1,2,…,N. Using the matrix geometric solution method and semi-Markov process, we obtain the distributions of the stationary system size at both arrival and arbitrary epochs. The distribution of the stationary waiting time of an arbitrary customer is also derived. In addition, we present some performance measures such as mean waiting time of an arbitrary customer, mean length of the type-i cycle, and mean number of customers in the system at the end of phase 0. Finally, some numerical examples are presented.

  11. Optimization of an M/M/1/N Feedback Queue with Retention of Reneged Customers

    Directory of Open Access Journals (Sweden)

    Rakesh Kumar

    2014-01-01

    Full Text Available Customer impatience has become a threat to the business world. Firms employ various customer retention strategies to retain their impatient (or reneged customers. Customer retention mechanisms may help to retain some or all impatient customers. Further, due to unsatisfactory service, customers may rejoin a queue immediately after departure. Such cases are referred to as feedback customers. Kumar and Sharma take this situation into account and study an M/M/1/N feedback queuing system with retention of reneged customers. They obtain only a steady-state solution for this model. In this paper, we extend the work of Kumar and Sharma by performing an economic analysis of the model. We develop a model for the costs incurred and perform the appropriate optimization. The optimum system capacity and optimum service rate are obtained. (original abstract

  12. Atomic spectroscopy with twisted photons: Separation of M 1 -E 2 mixed multipoles

    Science.gov (United States)

    Afanasev, Andrei; Carlson, Carl E.; Solyanik, Maria

    2018-02-01

    We analyze atomic photoexcitation into the discrete states by twisted photons, or photons carrying extra orbital angular momentum along their direction of propagation. From the angular momentum and parity considerations, we are able to relate twisted-photon photoexcitation amplitudes to their plane-wave analogs, independently of the details of the atomic wave functions. We analyze the photoabsorption cross sections of mixed-multipolarity E 2 -M 1 transitions in ionized atoms and found fundamental differences coming from the photon topology. Our theoretical analysis demonstrates that it is possible to extract the relative transition rates of different multipolar contributions by measuring the photoexcitation rate as a function of the atom's position (or impact parameter) with respect to the optical vortex center. The proposed technique for separation of multipoles can be implemented if the target's atom position is resolved with subwavelength accuracy; for example, with Paul traps. Numerical examples are presented for Boron-like highly charged ions.

  13. Occurrence of Aflatoxin M1 in Dairy Products in Southern Italy

    Directory of Open Access Journals (Sweden)

    Giovanna Barbuti

    2008-12-01

    Full Text Available A screening survey of the presence of aflatoxin M1 (AFM1 was carried out on 265 samples of cheese made from cow, buffalo, goat, sheep, sheep-goat milk collected in the Apulia region (Southern Italy. Selected samples included unripened, medium and long-term ripened cheeses. AFM1 was found in 16.6% of the analyzed samples. The highest positive incidence was for medium and long-term ripened cheeses, especially those made from sheep-goat milk, while buffalo cheeses tested consistently negative. Our results show that the level of contamination by AFM1 in dairy products from Apulia Region are lower than in other Italian and European regions. Moreover, it is important to underline that a common European norm concerning the AFM1 threshold limits for dairy products is still lacking.

  14. Radiative rates for E1, E2, M1 and M2 transitions in Fe X

    International Nuclear Information System (INIS)

    Aggarwal, K.M.; Keenan, F.P.

    2004-01-01

    Energies of the 54 levels belonging to the (1s 2 2s 2 2p 6 ) 3s 2 3p 5 , 3s3p 6 , 3s 2 3p 4 3d and 3s3p 5 3d configurations of Fe X have been calculated using the GRASP code of Dyall and colleagues (1989). Additionally, radiative rates, oscillator strengths, and line strengths are calculated for all electric dipole (E1), magnetic dipole (M1), electric quadrupole (E2), and magnetic quadrupole (M2) transitions among these levels. Comparisons are made with results available in the literature, and the accuracy of the data is assessed. Our energy levels are estimated to be accurate to better than 3%, whereas results for other parameters are probably accurate to better than 20% . Additionally, the agreement between measured and calculated lifetimes is better than 10%. (authors)

  15. E2 and M1 Transition Probabilities in Odd Mass Hg Nuclei

    Energy Technology Data Exchange (ETDEWEB)

    Berg, V; Baecklin, A; Fogelberg, B; Malmskog, S G

    1969-10-15

    L- and M-subshell ratios have been measured for the 39.5 keV transition in {sup 193}Hg and the 37.1 and 16.2 keV transitions in {sup 195}Hg yielding 0.38 {+-} 0.12 , <0.02 and 0.08 {+-} 0.03 per cent E2, respectively. The half-lives of the 39.5 keV level in {sup 193}Hg and the 53.3 and 37.1 keV levels in {sup 195}Hg have been measured by the delayed coincidence method, yielding values of 0.63 {+-} 0.03, 0.72 {+-} 0.03 and <0.05 nsec respectively. A systematic compilation of reduced E2 and M1 transition probabilities in odd mass Pt, Hg and Pb nuclei is given and compared to theoretical predictions.

  16. Aflatoxin M1 in buffalo and cow milk in Afyonkarahisar, Turkey.

    Science.gov (United States)

    Kara, Recep; Ince, Sinan

    2014-01-01

    Potential hazardous human exposure to aflatoxin M1 (AFM1) via consumption of milk and milk products has been demonstrated by many researchers. The aim of this study was to investigate the presence of this mycotoxin in buffalo and cow milk samples in the city of Afyonkarahisar, Turkey. For this purpose, 126 buffalo and 124 cow milk samples were collected from dairy farms in Afyonkarahisar province. AFM1 levels were determined by high-performance liquid chromatography with tandem mass spectrometric detection. Although AFM1 was not detected in cow milk samples, AFM1 was found above the limit of detection (milk samples. The results of this study indicated the importance of continuous surveillance of commonly consumed milk or milk product samples for AFM1 contamination in Turkey.

  17. Mutagenesis in yam, Discorea rotundata: Clonal evaluation of M1V3 yam plants

    International Nuclear Information System (INIS)

    Nwachukwu, E.C.; Mbanso, E.N.; Ene, L.S.O.

    1997-01-01

    Ten thousand plants of M 1 V 3 population of the white guinea yam, Dioscorea rotundata Poir, were evaluated. There was no consistent trends in variations in plant height, number of branches, branching heights and number of leaves of the treated tubers. However, plant height were lower in the irradiated than in the control. The coefficients of variations (C.V.) were higher in the irradiated than in the control populations, indicating wider variations in the former population. Based on yield performance, 110 tubers were selected for preliminary yield trials, Considering that diplontic selection may occur in the irradiated micro-tubers, the experiment will also be carried out using nodal cultures in vitro. (author). 2 tabs

  18. The MCNP Simulation of a PGNAA System at TRR-1/M1

    Science.gov (United States)

    Sangaroon, S.; Ratanatongchai, W.; Picha, R.; Khaweerat, S.; Channuie, J.

    2017-06-01

    The prompt-gamma neutron activation analysis system (PGNAA) has been installed at Thai Research Reactor-1/Modified 1 (TRR-1/M1) since 1999. The purpose of the system is for elemental and isotopic analyses. The system mainly consists of a series of the moderator and collimator, neutron and gamma-ray shielding and the HPGe detector. In this work, the condition of the system is carried out based on the Monte Carlo method using Monte Carlo N-Particle transport code and the experiment. The flux ratios (Φthermal/Φepithermal and Φthermal/Φfast) and thermal neutron flux have been obtained. The simulated prompt gamma rays of the Portland cement sample have been carried out. The simulation provides significant contribution in upgrading the PGNAA station to be available in various applications.

  19. M1 transitions between low-lying states in the sdg-IBM-2

    Science.gov (United States)

    Casperson, Robert; Werner, Volker

    2006-10-01

    The interplay between collective and single-particle degrees of freedom for nuclei in the A=90 region have recently been under investigation. In Molybdenum and Ruthenium nuclei, collective symmetric and mixed-symmetric structures have been identified, while in Zirconium, underlying shell-structure plays an enhanced role. Collective symmetric structures appear when protons and neutrons are in phase, whereas mixed-symmetric structures occur when they are not. The one-phonon 2^+ mixed-symmetric state was identified from strong M1 transitions to the 2^+1 state. Similar transitions were observed between higher-spin states, and are predicted by the shell model. These phenomena will be investigated within the sdg Interacting Boson Model 2 in order to obtain a better understanding about the structure of the states involved, and results from first model calculations will be presented. Work supported by US DOE under grant number DE-FG02-91ER-40609.

  20. An Automatic Detection Method of Nanocomposite Film Element Based on GLCM and Adaboost M1

    Directory of Open Access Journals (Sweden)

    Hai Guo

    2015-01-01

    Full Text Available An automatic detection model adopting pattern recognition technology is proposed in this paper; it can realize the measurement to the element of nanocomposite film. The features of gray level cooccurrence matrix (GLCM can be extracted from different types of surface morphology images of film; after that, the dimension reduction of film can be handled by principal component analysis (PCA. So it is possible to identify the element of film according to the Adaboost M1 algorithm of a strong classifier with ten decision tree classifiers. The experimental result shows that this model is superior to the ones of SVM (support vector machine, NN and BayesNet. The method proposed can be widely applied to the automatic detection of not only nanocomposite film element but also other nanocomposite material elements.

  1. Low pressure injection sequence sensitivity study of the M1 module of MEDICI

    International Nuclear Information System (INIS)

    Corradini, M.L.; Moses, G.A.; Norkus, J.K.; Welzbacker, R.T.

    1985-01-01

    In order to assess the consequences of a PWR containment failure and the ensuing radiological source term following a severe reactor accident, it is necessary to understand the ex-vessel behavior of the molten core. The M1 module of MEDICI models the dynamic fuel-coolant mixing, energetic interaction, and ejection of fuel and coolant from the reactor cavity following such an accident. A sensitivity study of the low pressure injection sequence was performed utilizing a Box-Behnken statistical design to treat five sets of input variables considered to be significant in the mixing and steam explosion processes. The low pressure injection sequence was studied in which the molten corium is modeled as a pour stream entering the cavity without entraining or sweeping out fuel or coolant

  2. The frequency of occurrence of aflatoxin M1 in milk on the territory of Vojvodina

    Directory of Open Access Journals (Sweden)

    Polovinski-Horvatović Miroslava S.

    2009-01-01

    Full Text Available Aflatoxin is one of the most common mycotoxins which can be found in milk. It represents a natural metabolite of aflatoxin B1 that occurs as a result of animal metabolism and the body's attempt to detoxificate it. It is excreted in milk, feces and urine of animals that consumed contaminated feed with aflatoxin B1. The carry-over from feed to milk depends on many factors, ranging from 0.3 to 6.2%. Aflatoxin M1 is in the first group of carcinogens according to the IRAC classification from 2002, but it is considered to have only 10% of carcinogenicity from its precursor aflatoxin B1. Legislation in member countries of European Union for this mycotoxin in milk intended for people is 0.05 μg/l, while the rest of the countries that also have legislation for this mycotoxin allow the concentration that is ten times higher, and that is 0.5 μg/l. In this paper, we have tried to provide on insight into the quality of milk, food often consumed by children, from the standpoint of mycotoxicology, and to compare the obtained data with data available from literature, from countries in the region that have similar climatic and agricultural conditions. From a total of 65 samples of processed milk, aflatoxin M1 was found in 18 samples and none of the samples exceeded the level of 0.05 μg/l, which is allowed by the legislation of the European Union.

  3. Effect of closed shells on the multipole mixing parameter δ(E2/M1)

    International Nuclear Information System (INIS)

    Morozov, V.A.

    1992-01-01

    The behavior of the magnitude and sign of the mixing parameter δ(E2/M1) in even-even nuclei has been studied in a number of papers. The most extensive data has been given for transitions of the type 3 γ + , 2 γ + , 2 β + →2 g + . The data on δ are relatively scarce for mixed transitions in odd nuclei with magic or semimagic cores. However, certain conclusions can be drawn about the behavior of δ in transitions in odd nuclei near magic numbers, and also in transitions in even-even nuclei when passing through quasishells: (1) the absolute value of the reduced mixing parameter in transitions between particle and cluster-vibrational states in odd nuclei decreases as a closed shell is approached; (2) δ has the same sign for transitions between particle and cluster-vibrational levels in nuclei with Z=83 and 85 and N=83, 85, and 87; (3) in odd nuclei the sign of δ is positive for transitions between positive-parity states s 1/2 -d 3/2 in Cd, Sm, and Tl isotopes and is negative for transitions between negative-parity states f 7/2 π and h 9/2 π in Sm, Gd, Bi, and At isotopes, independently of whether these transitions are neutron or proton transitions; (4) the removal of ±2 nucleons in an even shell from a magic core (and in certain nuclei a larger number of pairs of nucleons) does not lead to a change in sign of δ in transitions producing an odd nucleus; (5) the closure of quasishells at N=96 and 104 in even-even nuclei is associated with an increase in the absolute value of δ(E2/M1)/E γ , but the sign of δ does not change

  4. Phenotype and molecular analysis of M1 generation of stylosanthes irradiated by 60Co

    International Nuclear Information System (INIS)

    Zhang Weili; Liu Fengmin

    2012-01-01

    The seeds of Stylosanthes guianensis SW. ‘Reyan No.13’ were irradiated by 60 Co at 0, 325, 487 and 974 Gy. Phenotype and molecular variations of Stylosanthes M 1 generations were studied. Germination percentage, plant height, leaf length and stem diameter of M 1 seedlings were determined using SRAP-PCR. Results showed that biological character indices of treatments were significantly lower than that of control (CK). Irradiation inhibited plant growth. Growth indices of 974 Gy treatment, except leaf length, were significantly lower than CK and other two treatments. Eight effective primers selected from 24 primers combination were used for SRAP-PCR. SRAP analysis revealed that the 57 of 88 DNA fragments were amplified showing polymorphisms. The average percentage of polymorphic bands was 64.77%. The effects of 60 Coγ irradiation on DNA variation of seedlings were varied from different treatments. Numbers of polymorphic bands changed after irradiation. Coefficient of variation was in direct proportion to irradiation doses. Variation rates of 325 Gy, 487 Gy and 974 Gy treatments were 22.0%, 38.1% and 41.5%, respectively. The Nei’s genetic similarity coefficient of all treatments was ranged from 0.585 to 0.780 by software NTSYSpc 2.1 based on SRAP results and the average Nei's coefficient was 0.678. The Nei’s genetic similarity coefficient of 974 Gy treatment was 0.585 and variation degree was highest among all treatments, 487 Gy treatment was second and 325 Gy treatment was the lowest one. Based on present bands, four irradiated treatments were classified into two major groups by UPGMA cluster analysis. Group 1 included CK, 325 Gy and 487 Gy treatment and group 2 included 974 Gy. SRAP analysis determined variation of Stylosanthes after irradiation and the results of SRAP analysis were consistent with their biological indexes in some extent

  5. Single-channel ground airborne radio system (SINCGARS) based remote control for the M1 Abrahms

    Science.gov (United States)

    Urda, Joseph R.

    1995-04-01

    Remote control of the Ml Abrahms Main Battle Tank through a minefield breach operation will remove the vehicle crew from the inherent hazard. A successful remote control system will provide automotive control yet not impair normal operation. This requires a minimum of physical parts, and an unobtrusive installation. Most importantly, a system failure must not impair the regular operation as a manned system. The system itself need not be complex. A minefield breach only requires simple control of automotive function and a mine plow interface. Control hardware for the Ml-Al can be reduced to two linear actuators, an electrical interface for the engine control unit, an interface for the mine plow, and the associated cables. Communication between vehicle control and operator control takes place over the vehicles organic radio (typically SINCGARS). This helps reduce the number of special purpose components for the remote control device. The device is currently awaiting an automotive safety test to prepare for its safety release. Because of the specific nature of the MDL-STD 1553-B data bus the device will not control an M1-A2 Main Battle Tank. The architecture will allow control of the M1-A2 through the 1553-B data bus however the physical hardware has not been constructed. The control scheme will not change. The communication interface will provide greater flexibility when interfacing to the vehicle tactical radio. Operational utility will be determined by U.S. Army Training and Doctrine Command personnel. The obvious benefit is that if a remote tank is lost during a minefield breach the crew is saved.

  6. In Vivo Measurements in Mice in the Bion-M 1 Mission

    Science.gov (United States)

    Andreev-Andrievskiy, Alexander; Custaud, Marc-Antoine; Popova, Anfisa; Borovik, Anatoliy; Dolgov, Oleg; Anokhin, Konstantin; Tsvirkun, Daria; Vinogradova, Olga

    The main aim of BION-M 1 mission was to reveal morphological, biochemical and molecular mechanisms of adaptation to prolonged exposure in microgravity. Besides that functional state and behavior were assessed in vivo using test battery, home cage observations and implantable telemetry in space-flown mice (SF), control mice from the ground replica of the flight experiment (GC) and in mice kept in vivarium (SFV and GCV). Blood pressure and heart rate were monitored continuously in a subgroup of mice using implantable telemetry throughout the flight as well as before and after it. After 30-days flight aboard BION-M 1 biosatellite SF mice have gained more weight than GC, SFV or GCV mice (11%). SF mice displayed pronounced motor impairment upon examination shortly after landing. 1 day after the flight mice were less active and more anxious in the open-field test, less coordinated in the Rotarod and aerial drop test and had less grip force compared to both control and pre-flight values. Exercise performance was greatly reduced after 30-days flight and recovered by day 7 post-flight. Before the flight mice were trained to perform a simple task using positively reinforced free operant conditioning approach. After the flight performance in the same task was preserved, however learning ability was impaired. Mice displayed drastic reduction of heart rate during launch and reentry acceleration periods. Heart rate (by 8-10%) and, to a lesser extent blood pressure (by 5%) were elevated during the 30-days flight. After return heart rate in SF mice remained elevated throughout the 7-days observation period with no apparent recovery. In summary, mice display pronounced disadaptation to 1g after 30-days exposure in microgravity with different physiological systems having different recovery dynamics. Of particular interest, hemodynamic reactions in mice closely resemble reactions in larger organisms, implying that factors that govern the cardiovascular system adaptation to

  7. Proteoglycan biosynthesis in murine monocytic leukemic (M1) cells before and after differentiation

    International Nuclear Information System (INIS)

    McQuillan, D.J.; Yanagishita, M.; Hascall, V.C.; Bickel, M.

    1989-01-01

    Murine monocytic leukemic (M1) cells were cultured in the presence of [ 3 H]glucosamine and [ 35 S]sulfate. Labeled proteoglycans were purified by anion exchange chromatography and characterized by gel filtration and sodium dodecyl sulfate-polyacrylamide gel electrophoresis in combination with chemical and enzymatic degradation. M1 cells synthesize a single predominant species of proteoglycan which distributes almost equally between the cell and medium after 17 h labeling. The cell-associated proteoglycan has an overall size of about 135 kDa and contains three to five chondroitin sulfate chains (28-31 kDa each) attached to a chondroitinase-generated core protein of 28 kDa. The synthesis and subsequent secretion of this proteoglycan was enhanced 4-5-fold in cells induced to differentiate into macrophages. This was not a phenomenon of arrest in the G0/G1 stage of the cell cycle, since density inhibited undifferentiated cells arrested at this stage did not increase proteoglycan synthesis. The chondroitin sulfate chains contained exclusively chondroitin 4- and 6-sulfate; however, the ratio of these two disaccharides differed between the medium- and cell-associated proteoglycans, and changed during progression of the cells into a fully differentiated phenotype. Pulse-chase kinetics indicate the presence of two distinct pools of proteoglycan; one that is secreted very rapidly from the cell after a approximately 1-h lag, and a second pool that is turned over in the cell with a half-time of approximately 3.5 h. Subtle differences in the glycosylation patterns of the medium- and cell-associated species are consistent with synthesis of two pools. Papain digestion suggests that the chondroitin sulfate chains are clustered on a small protease resistant peptide. The data suggest that this proteoglycan is similar to the serglycin proteoglycan family

  8. HLA-B27M1M2 and high immune responsiveness to Shigella flexneri in post-dysenteric arthritis

    NARCIS (Netherlands)

    van Bohemen, C. G.; Nabbe, A. J.; Landheer, J. E.; Grumet, F. C.; Mazurkiewicz, E. S.; Dinant, H. J.; Lionarons, R. J.; van Bodegom, P. C.; Zanen, H. C.

    1986-01-01

    The heterogeneous HLA-B27 antigen is closely associated with post-infectious or reactive arthritis (ReA) and is comprised of two serologically defined variants: B27M1+M2+ and B27M1+M2-. An outbreak of dysentery (n = 120) caused by a Shigella flexneri 2a strain, which possessed cell envelope antigens

  9. Uncovering SUMOylation Dynamics during Cell-Cycle Progression Reveals FoxM1 as a Key Mitotic SUMO Target Protein

    DEFF Research Database (Denmark)

    Schimmel, Joost; Eifler, Karolin; Sigurdsson, Jón Otti

    2014-01-01

    Loss of small ubiquitin-like modification (SUMOylation) in mice causes genomic instability due to the missegregation of chromosomes. Currently, little is known about the identity of relevant SUMO target proteins that are involved in this process and about global SUMOylation dynamics during cell......-cycle progression. We performed a large-scale quantitative proteomics screen to address this and identified 593 proteins to be SUMO-2 modified, including the Forkhead box transcription factor M1 (FoxM1), a key regulator of cell-cycle progression and chromosome segregation. SUMOylation of FoxM1 peaks during G2 and M...... relieving FoxM1 autorepression. Cells deficient for FoxM1 SUMOylation showed increased levels of polyploidy. Our findings contribute to understanding the role of SUMOylation during cell-cycle progression....

  10. Identification of the yeast gene encoding the tRNA m1G methyltransferase responsible for modification at position 9.

    Science.gov (United States)

    Jackman, Jane E; Montange, Rebecca K; Malik, Harmit S; Phizicky, Eric M

    2003-05-01

    Methylation of tRNA at the N-1 position of guanosine to form m(1)G occurs widely in nature. It occurs at position 37 in tRNAs from all three kingdoms, and the methyltransferase that catalyzes this reaction is known from previous work of others to be critically important for cell growth in Escherichia coli and the yeast Saccharomyces cerevisiae. m(1)G is also widely found at position 9 in eukaryotic tRNAs, but the corresponding methyltransferase was unknown. We have used a biochemical genomics approach with a collection of purified yeast GST-ORF fusion proteins to show that m(1)G(9) formation of yeast tRNA(Gly) is associated with ORF YOL093w, named TRM10. Extracts lacking Trm10p have undetectable levels of m(1)G(9) methyltransferase activity but retain normal m(1)G(37) methyltransferase activity. Yeast Trm10p purified from E. coli quantitatively modifies the G(9) position of tRNA(Gly) in an S-adenosylmethionine-dependent fashion. Trm10p is responsible in vivo for most if not all m(1)G(9) modification of tRNAs, based on two results: tRNA(Gly) purified from a trm10-Delta/trm10-Delta strain is lacking detectable m(1)G; and a primer extension block occurring at m(1)G(9) is removed in trm10-Delta/trm10-Delta-derived tRNAs for all 9 m(1)G(9)-containing species that were testable by this method. There is no obvious growth defect of trm10-Delta/trm10-Delta strains. Trm10p bears no detectable resemblance to the yeast m(1)G(37) methyltransferase, Trm5p, or its orthologs. Trm10p homologs are found widely in eukaryotes and many archaea, with multiple homologs in several metazoans, including at least three in humans.

  11. Absolute M1 and E2 Transition Probabilities in 233U

    International Nuclear Information System (INIS)

    Malmskog, S.G.; Hoejeberg, M.

    1967-08-01

    Using the delayed coincidence technique, the following half lives have been determined for different excited states in 233 U: T 1/2 (311.9 keV level) = (1.20 ± 0.15) x 10 -10 sec, T 1/2 (340.5 keV level) = (5.2 ± 1.0) x 10 -11 sec, T 1/2 (398.6 keV level) = (5.5 ± 2.0) x 10 -11 sec and T 1/2 (415.8 keV level) -11 sec. From these half life determinations, together with earlier known electron intensities and conversion coefficients, 22 reduced B(Ml) and B(E2) transition probabilities (including 9 limits) have been deduced. The rotational transitions give information on the parameters δ and (g K - g R ) . The experimental M1 and E2 transition rates between members of different bands have been analysed in terms of the predictions of the Nilsson model, taking also pairing correlations and Coriolis coupling effects into account

  12. Contamination profile of aflatoxin M1 residues in milk supply chain of Sindh, Pakistan

    Directory of Open Access Journals (Sweden)

    Sana Jawaid

    2015-01-01

    Full Text Available Aflatoxin M1 (AFM1 is a potent carcinogen, teratogen and mutagen found in the milk when lactating animals consume feed contaminated with aflatoxin B1 (AFB1. In the present study, the contamination of AFM1 was evaluated in the milk supply chain of the province of Sindh, Pakistan. For the broader profiling of targeted toxin, enzyme-linked immunosorbent assay (ELISA was used for the determination of AFM1 in both branded and non-branded milk samples. The results showed that 96.43% of samples (81 out of 84 were contaminated with AFM1 in the range of 0.01–0.76 μg/L. The average contamination level was 0.38 μg/L. The determined values of AFM1 in the collected milk samples were above the standard limit of the European Commission while 70% of the samples exceeded levels established by United States regulations. According to these results, the estimated daily intake of AFM1 for adults was determined as 3.1 ng/kg of body weight per day.

  13. Pancreatic Resections for Advanced M1-Pancreatic Carcinoma: The Value of Synchronous Metastasectomy

    Directory of Open Access Journals (Sweden)

    S. K. Seelig

    2010-01-01

    Materials and Methods. From January 1, 2004 to December, 2007 a total of 20 patients with pancreatic malignancies were retrospectively evaluated who underwent pancreatic surgery with synchronous resection of hepatic, adjacent organ, or peritoneal metastases for proven UICC stage IV periampullary cancer of the pancreas. Perioperative as well as clinicopathological parameters were evaluated. Results. There were 20 patients (9 men, 11 women; mean age 58 years identified. The primary tumor was located in the pancreatic head (n=9, 45%, in pancreatic tail (n=9, 45%, and in the papilla Vateri (n=2, 10%. Metastases were located in the liver (n=14, 70%, peritoneum (n=5, 25%, and omentum majus (n=2, 10%. Lymphnode metastases were present in 16 patients (80%. All patients received resection of their tumors together with metastasectomy. Pylorus preserving duodenopancreatectomy was performed in 8 patients, distal pancreatectomy in 8, duodenopancreatectomy in 2, and total pancreatectomy in 2. Morbidity was 45% and there was no perioperative mortality. Median postoperative survival was 10.7 months (2.6–37.7 months which was not significantly different from a matched-pair group of patients who underwent pancreatic resection for UICC adenocarcinoma of the pancreas (median survival 15.6 months; P=.1. Conclusion. Pancreatic resection for M1 periampullary cancer of the pancreas can be performed safely in well-selected patients. However, indication for surgery has to be made on an individual basis.

  14. CP and CP-PGN protect mice against MRSA infection by inducing M1 macrophages.

    Science.gov (United States)

    Zhang, Yang; Li, Xiang-Xiang; Ma, Yuan; Xu, Jie; Zhao, Li-Na; Qian, Xue-Feng; Zhang, Xian-Feng; Shi, Jin-Fang; Han, Qing-Zhen

    2017-12-04

    Corynebacterium pyruviciproducens (C. pyruviciproducens, CP), as a newly discovered immunomodulator, has been confirmed to have a stronger immunoregulation than Propionibacterium acnes (P. acnes) of the traditional immune adjuvant, by previous experiments with model antigen ovalbumin and sheep red blood cells. Here, it was designed to assess its ability to resist methicillin-resistant Staphylococcus aureus (MRSA), since MRSA as a vital gram positive pathogen is characterized by high morbidity and mortality. In this report, it was indicated that C. pyruviciproducens and its peptidoglycan (CP-PGN) could help to be against bloodstream infection of MRSA with raised survival rate, decreased bacteria load and alleviated systemic inflammation, and these effects of CP-PGN were more pronounced. However, the whole CP was inclined to prevent localized abdominal infection of MRSA from progressing to a systemic infection. And they showed the potential as a therapeutic drug alone or combined with vancomycin. The diversity of capacity of activating macrophages induced by CP and CP-PGN may result in distinct resistance to MRSA in different infection models. Furthermore, both CP and CP-PGN induced M1 macrophages. In conclusion, CP and its PGN could act as promising immune agents to treat and prevent MRSA infection.

  15. Rates of E1, E2, M1, and M2 transitions in Ni II

    Science.gov (United States)

    Cassidy, C. M.; Hibbert, A.; Ramsbottom, C. A.

    2016-03-01

    Aims: We present rates for all E1, E2, M1, and M2 transitions among the 295 fine-structure levels of the configurations 3d9, 3d84s, 3d74s2, 3d84p, and 3d74s4p, determined through an extensive configuration interaction calculation. Methods: The CIV3 code developed by Hibbert and coworkers is used to determine for these levels configuration interaction wave functions with relativistic effects introduced through the Breit-Pauli approximation. Results: Two different sets of calculations have been undertaken with different 3d and 4d functions to ascertain the effect of such variation. The main body of the text includes a representative selection of data, chosen so that key points can be discussed. Some analysis to assess the accuracy of the present data has been undertaken, including comparison with earlier calculations and the more limited range of experimental determinations. The full set of transition data is given in the supplementary material as it is very extensive. Conclusions: We believe that the present transition data are the best currently available. Full Table 4 and Tables 5-8 are only available at the CDS via anonymous ftp to http://cdsarc.u-strasbg.fr (ftp://130.79.128.5) or via http://cdsarc.u-strasbg.fr/viz-bin/qcat?J/A+A/587/A107

  16. Aflatoxin B1 and M1: Biological Properties and Their Involvement in Cancer Development

    Directory of Open Access Journals (Sweden)

    Silvia Marchese

    2018-05-01

    Full Text Available Aflatoxins are fungal metabolites found in feeds and foods. When the ruminants eat feedstuffs containing Aflatoxin B1 (AFB1, this toxin is metabolized and Aflatoxin M1 (AFM1 is excreted in milk. International Agency for Research on Cancer (IARC classified AFB1 and AFM1 as human carcinogens belonging to Group 1 and Group 2B, respectively, with the formation of DNA adducts. In the last years, some epidemiological studies were conducted on cancer patients aimed to evaluate the effects of AFB1 and AFM1 exposure on cancer cells in order to verify the correlation between toxin exposure and cancer cell proliferation and invasion. In this review, we summarize the activation pathways of AFB1 and AFM1 and the data already reported in literature about their correlation with cancer development and progression. Moreover, considering that few data are still reported about what genes/proteins/miRNAs can be used as damage markers due to AFB1 and AFM1 exposure, we performed a bioinformatic analysis based on interaction network and miRNA predictions to identify a panel of genes/proteins/miRNAs that can be used as targets in further studies for evaluating the effects of the damages induced by AFB1 and AFM1 and their capacity to induce cancer initiation.

  17. Absolute M1 and E2 Transition Probabilities in 2{sup 33}U

    Energy Technology Data Exchange (ETDEWEB)

    Malmskog, S G; Hoejeberg, M

    1967-08-15

    Using the delayed coincidence technique, the following half lives have been determined for different excited states in {sup 233}U: T{sub 1/2} (311.9 keV level) = (1.20 {+-} 0.15) x 10{sup -10} sec, T{sub 1/2} (340.5 keV level) = (5.2 {+-} 1.0) x 10{sup -11} sec, T{sub 1/2} (398.6 keV level) = (5.5 {+-} 2.0) x 10{sup -11} sec and T{sub 1/2} (415.8 keV level) < 3 x 10{sup -11}sec. From these half life determinations, together with earlier known electron intensities and conversion coefficients, 22 reduced B(Ml) and B(E2) transition probabilities (including 9 limits) have been deduced. The rotational transitions give information on the parameters {delta} and (g{sub K} - g{sub R}) . The experimental M1 and E2 transition rates between members of different bands have been analysed in terms of the predictions of the Nilsson model, taking also pairing correlations and Coriolis coupling effects into account.

  18. Monitoring of aflatoxin M1 in raw cow milk in Croatia during winter 2015

    Directory of Open Access Journals (Sweden)

    Nina Bilandžić

    2016-01-01

    Full Text Available A total of 548 raw milk samples were collected in the western, central and eastern regions of Croatia during February and March 2015. Aflatoxin M1 (AFM1 concentrations were quantified by the enzyme immunoassay method. The method limits of detection (LOD and quantification (LOQ were 22.2 and 34.2 ng/kg, respectively. The mean AFM1 levels measured in the three regions were (ng/kg as follows: western 3.69, central 3.11 and eastern 4.14. In total, the 548 samples analysed concentrations were below the LOD value and accordingly below the European Union maximum residue level (EU MRL of 50 ng/kg. The results suggest an absence of use of contaminated with aflatoxin B1 supplementary feedstuff for lactating cows in winter 2015. Such results might be related to the improved storage conditions for feed as well as to the enhanced and more stringent feed control system for mycotoxins in Croatia.

  19. Aflatoxin M1 in Pasteurized Milk in Babol city, Mazandaran Province, Iran.

    Science.gov (United States)

    Sefidgar, Saa; Mirzae, M; Assmar, M; Naddaf, Sr

    2011-01-01

    Aflatoxin M(1) (AFM(1)) is the metabolite of aflatoxin B1 (AFB(1)) and is found in milk when lactating animals are fed with contaminated feedstuff. The presence of AFM(1) in milk, pose a major risk for humans especially kids as it can have immunosuppressive, mutagenic, teratogenic and carcinogenic effects. The present study is aimed to investigate the occurrence of AFM(1) in subsidized pasteurized milk in Babol, Mazandaran Province, Iran. Some 72 pasteurized milk packages were collected from supermarkets in various districts of city during January to March 2006. Milk samples were centrifuged and amounts of 100 μl of skimmed milk were tested for AFM(1) contamination by competitive ELISA. All the samples (100%) exhibited contamination with AFM(1). The contamination levels means in January, February, and March were 227.85, 229.64, and 233.1ng/l, respectively. The amount of AFM(1) in all the samples were above 50ng/l, the threshold set by the European community regulations. Monitoring of AFM(1) level should be part of quality control procedures in dairy factories, particularly the ones providing infant's milk. Production of safer and healthier milk and other dairy products with minimum AFM(1) level can be achieved by adopting prophylactic measures including control of humidity and water content of feedstuff, which favors mould production.

  20. Aflatoxin M1 in milk by immunoaffinity column cleanup with TLC/HPLC determination

    Directory of Open Access Journals (Sweden)

    Shundo Luzia

    2006-01-01

    Full Text Available During 2002 and 2003, a total of 107 samples of raw, pasteurized and ultrahigh treated temperature (UHT milk commercialized in the cities of São Paulo and Marília (SP were analyzed for the presence of aflatoxin M1 (AFM1. AFM1 was detected in 79 (73.8% of milk samples, ranging from <0.02 to 0.26 mug/L.The samples were analyzed using an immunoaffinity column for cleanup and a thin layer chromatography for determining AFM1. The parameters, such as recovery, repeatibility, detection and quantification limit were evaluated to optimize this method (in-house. Based on spiked samples, the recovery values ranged from 85.83 to 73.86% at levels of 0.010-0.50 mug/L, respectively, and the relative standard deviation for repeatibility ranged from 7.73 to 2.08%. The quantification limit was 0.02 mug/L. The results of some samples analyzed by this method demonstrated a satisfatory correlation when compared with High Performance Liquid Chromatography (HPLC. In conclusion, immunoaffinity column cleanup gave excellent results for recovery, sensibility and sample through put. Despite the high rate of occurrence of AFM1 in samples in both cities, the contamination level could not be considered a serious public health hazard, according to Brazilian legislation.

  1. A survey of aflatoxin M1 in cow milk in Southern Iran

    Directory of Open Access Journals (Sweden)

    Majid Hashemi

    2016-10-01

    Full Text Available The competitive enzyme-linked immunosorbent assay technique was used to evaluate aflatoxin M1 (AFM1 levels in 168 samples of raw milk (135 samples and 33 samples from bulk tanks of farms and milk collection centers, respectively and 12 samples of pasteurized milk in Fars province, Southern Iran. AFM1 was found in 55.56% of the samples with a mean concentration of 21.31 ng/L. The concentration of AFM1 in raw milk samples from farms was significantly (p < 0.05 lower than that in samples from collection centers and pasteurized milk. The concentration of AFM1 was not influenced by season, location, or type of farm. The concentrations of AFM1 in all samples were lower than the Iranian national standard limit (100 ng/L, but in 30% of raw cow milk samples they were higher than the maximum tolerance limit accepted by the European Union (50 ng/L; therefore, more effort is needed to control AFM1 levels in milk produced in Southern Iran.

  2. Development of an Electrochemical Biosensor for the Detection of Aflatoxin M1 in Milk

    Directory of Open Access Journals (Sweden)

    Jean-Louis Marty

    2010-10-01

    Full Text Available We have developed an electrochemical immunosensor for the detection of ultratrace amounts of aflatoxin M1 (AFM1 in food products. The sensor was based on a competitive immunoassay using horseradish peroxidase (HRP as a tag. Magnetic nanoparticles coated with antibody (anti-AFM1 were used to separate the bound and unbound fractions. The samples containing AFM1 were incubated with a fixed amount of antibody and tracer [AFM1 linked to HRP (conjugate] until the system reached equilibrium. Competition occurs between the antigen (AFM1 and the conjugate for the antibody. Then, the mixture was deposited on the surface of screen-printed carbon electrodes, and the mediator [5-methylphenazinium methyl sulphate (MPMS] was added. The enzymatic response was measured amperometrically. A standard range (0, 0.005, 0.01, 0.025, 0.05, 0.1, 0.25, 0.3, 0.4 and 0.5 ppb of AFM1-contaminated milk from the ELISA kit was used to obtain a standard curve for AFM1. To test the detection sensitivity of our sensor, samples of commercial milk were supplemented at 0.01, 0.025, 0.05 or 0.1 ppb with AFM1. Our immunosensor has a low detection limit (0.01 ppb, which is under the recommended level of AFM1 [0.05 µg L-1 (ppb], and has good reproducibility.

  3. Distribution and stability of Aflatoxin M1 during processing and ripening of traditional white pickled cheese.

    Science.gov (United States)

    Oruc, H H; Cibik, R; Yilmaz, E; Kalkanli, O

    2006-02-01

    The distribution of aflatoxin M(1) (AFM(1)) has been studied between curd, whey, cheese and pickle samples of Turkish white pickled cheese produced according to traditional techniques and its stability studied during the ripening period. Cheeses were produced in three cheese-making trials using raw milk that was artificially contaminated with AFM(1) at the levels of 50, 250 and 750 ng/l and allowed to ripen for three months. AFM(1) determinations were carried out at intervals by LC with fluorescence detection after immunoaffinity column clean-up. During the syneresis of the cheese a proportionately high concentration of AFM(1) remained in curd and for each trial the level was 3.6, 3.8 and 4.0 times higher than levels in milk. At the end of the ripening, the distribution of AFM(1) for cheese/whey + brine samples was 0.9, 1.0 and 1.3 for first, second and third spiking respectively indicating that nearly half of the AFM(1) remained in cheese. It has been found that only 2-4% of the initial spiking of AFM(1) transferred into the brine solution. During the ripening period AFM(1) levels remained constant suggesting that AFM(1) was quite stable during manufacturing and ripening.

  4. Distribution of radiative strength with excitation energy: the E1 and M1 giant resonances

    International Nuclear Information System (INIS)

    Brown, G.E.; Speth, J.

    1979-01-01

    Calculations of the giant dipole resonance in the particle-hole model, employing empirical values for the unperturbed particle and hole energies, have been unsuccessful in pushing the dipole state to a sufficiently high energy. it is argued that unperturbed levels correspondign to an effective mass of m*/m approx. 0.6 to 0.7 should be employed. The couplings of particles and holes to vibrations are the crucial ingredients in these considerations. More generally, it is argued that the effective mass relevant to excitations near the Fermi surface is that corresponding to empirical single-particle levels, m*/m greater than or equal to 1.0. For particle-hole excitations above the Fermi surface, it is a decreasing function of excitation energy, reaching the above values 0.6 to 0.7 for E greater than or equal to 2 dirac constant/b omega, dirac constant/sub omega/ being the shell spacing. This has the consequence of spreading out the M1 strength. A new interpretation of experimental strengths is proposed

  5. CYP1A1 m1 and m2 polymorphisms: genetic susceptibility to lung cancer

    Directory of Open Access Journals (Sweden)

    Paula Mota

    2010-01-01

    Full Text Available Lung cancer is considered an environment-related disease that develops as a consequence of exposure to mutagenic agents, namely those present in tobacco. The CYP1A1 gene codifies the phase I enzyme aryl hydrocarbon hydroxilase (AHH belonging to the cytochrome P450 system that plays a major role in the bio-activation of tobacco procarcinogenes. Two CYP1A1 polymorphisms, m1 (T6235C transition and m2 (A4889G transition, are associated with greater enzymatic activity and have been described as genetic susceptibility factors for lung cancer.The aim of this study was to verify if this association holds true in blood samples of 175 lung cancer patients and 217 non-cancer patients from Portugal's midlands region. The samples were studied by restriction fragment length polymorphism (RFLP assay.The allelic frequencies of the mutant alleles were 0.12 for allele C and 1.14 for allele G in the control population. The results were not statistically different from those alleles in the patient population. There was also no statistically significant difference in genotype distribution in lung cancer patients and controls even when combining high risk genotypes. In our control sample, as in other populations of different ethnic origin, both polymorphisms also seem to be in linkage disequilibrium. We conclude that in this sample of the Portuguese population, CYP1A1 m1 and m2 polymorphisms are too rare to be of clinical relevance, and do not seem to be associated with susceptibility to lung cancer. Resumo: O cancro do pulmão é considerado uma doença relacionada com o meio ambiente, consequência da exposição a agentes mutagénicos, nomeadamente os presentes no fumo do tabaco. O gene CYP1A1 codifica a enzima aril hidrocarboneto hidroxilase (AHH, da fase I, do sistema multienzimático do citocromo P450, que desempenha uma função preponderante na bioactivação dos procarcinogénios do tabaco. Dois polimorfismos do CYP1A1, m1 (transi

  6. Development of an impedimetric aptasensor for the determination of aflatoxin M1 in milk.

    Science.gov (United States)

    Istamboulié, Georges; Paniel, Nathalie; Zara, Lorena; Reguillo Granados, Lucia; Barthelmebs, Lise; Noguer, Thierry

    2016-01-01

    An aptasensor was designed for the determination of aflatoxin M1 (AFM1) in milk based on DNA-aptamer recognition and electrochemical impedance spectroscopy detection. A hexaethyleneglycol-modified 21-mer oligonucleotide was immobilized on a carbon screen-printed electrode through carbodiimide immobilization, after diazonium activation of the sensing surface. Cyclic voltammetry and electrochemical impedance spectroscopy in the presence of ferri/ferrocyanide redox probe were used to characterize each step of the aptasensor development. Aptamer-AFM1 interaction induced an increase in electron-transfer resistance, allowing the determination of AFM1 in buffer in the range 2-150 ng/L (LOD=1.15 ng/L). Application to milk analysis showed that a preliminary treatment was mandatory. A simple filtration through a 0.2 µm PTFE membrane allowed determination of AFM1 in milk for concentrations ranging from 20 to 1000 ng/kg. These performances are compatible with the AFM1 levels set in European Union for milk and dairy products for adults (50 ng/kg) and infants (25 ng/kg). Copyright © 2015 Elsevier B.V. All rights reserved.

  7. Aflatoxin M1 levels in raw milk, pasteurised milk and infant formula

    Directory of Open Access Journals (Sweden)

    Sharaf S. Omar

    2016-06-01

    Full Text Available The incidence of contamination of aflatoxin M1 (AFM1 in milk samples collected from the Jordanian market was investigated by using the competitive enzyme linked immunosorbent assay (ELISA technique. A total of 175 samples were collected during 2014-2015. All tested samples were contaminated with various levels of AFM1 ranging from 9.71 to 288.68 ng/kg. The concentration of AFM1 in 66% of fresh milk samples was higher than the maximum tolerance limit accepted by the European Union (50 ng/kg and 23% higher than the maximum tolerance limit accepted by the US (500 ng/kg. Percentages of contaminated raw cow, sheep, goat and camel milk exceeding the European tolerance limit were 60, 85, 75 and 0%, respectively. Of AFM1 contaminated pasteurised cow milk samples, 12% exceeded the European tolerance limit with a range of contamination between 14.60 and 216.78 ng/kg. For infant formula samples, the average concentration of AFM1 was 120.26 ng/kg (range from 16.55 to 288.68 ng/kg, the concentration of AFM1 in 85% of infant formula samples was higher than the maximum tolerance limit accepted by the European Union and the US (25 ng/kg.

  8. Genomic Comparison among Lethal Invasive Strains of Streptococcus pyogenes Serotype M1

    Directory of Open Access Journals (Sweden)

    Gabriel R. Fernandes

    2017-10-01

    Full Text Available Streptococcus pyogenes, also known as group A Streptococcus (GAS, is a human pathogen that causes diverse human diseases including streptococcal toxic shock syndrome (STSS. A GAS outbreak occurred in Brasilia, Brazil, during the second half of the year 2011, causing 26 deaths. Whole genome sequencing was performed using Illumina platform. The sequences were assembled and genes were predicted for comparative analysis with emm type 1 strains: MGAS5005 and M1 GAS. Genomics comparison revealed one of the invasive strains that differ from others isolates and from emm 1 reference genomes. Also, the new invasive strain showed differences in the content of virulence factors compared to other isolated in the same outbreak. The evolution of contemporary GAS strains is strongly associated with horizontal gene transfer. This is the first genomic study of a Streptococcal emm 1 outbreak in Brazil, and revealed the rapid bacterial evolution leading to new clones. The emergence of new invasive strains can be a consequence of the injudicious use of antibiotics in Brazil during the past decades.

  9. Reduction of Aflatoxin M1 Levels during Ethiopian Traditional Fermented Milk (Ergo Production

    Directory of Open Access Journals (Sweden)

    Tsige Shigute

    2018-01-01

    Full Text Available In this study, the reduction of aflatoxin M1 (AFM1 levels during lab-scale ergo production was investigated through determination of the residual levels of AFM1 using Enzyme Linked Immunosorbent Assay. The results showed gradual and incubation time dependent reduction of AFM1 level in the raw milk samples being fermented to ergo. The maximum reductions of 57.33 and 54.04% were recorded in AFM1 in natural and LAB inoculums initiated fermentations, respectively, in 5 days of incubation. Although a significant difference (P=0.05 in the AFM1 decrease in the two types of fermentations was recorded, such findings could vary with milk samples depending on initial load of the microorganisms as determined by hygienic conditions. However, the level of AFM1 in control (sterilized samples showed only a 5.5% decrease during the entire period of incubation. Microbiological investigation showed increasing LAB counts with incubation time. A gradual decrease in pH of the milk samples was observed during fermentation. Considering the fact that both viable and dead bacterial cells could remove AFM1 during ergo production, the mechanism is proposed as predominantly involving noncovalent binding of the toxin with the chemical components of the bacterial cell wall.

  10. Medical students who decompress during the M-1 year outperform those who fail and repeat it: A study of M-1 students at the University of Illinois College of Medicine at Urbana-Champaign 1988–2000

    Directory of Open Access Journals (Sweden)

    Freund Gregory G

    2005-05-01

    Full Text Available Abstract Background All medical schools must counsel poor-performing students, address their problems and assist them in developing into competent physicians. The objective of this study was to determine whether students with academic deficiencies in their M-1 year graduate more often, spend less time to complete the curriculum, and need fewer attempts at passing USMLE Step 1 and Step 2 by entering the Decompressed Program prior to failure of the M-1 year than those students who fail the M-1 year and then repeat it. Method The authors reviewed the performance of M-1 students in the Decompressed Program and compared their outcomes to M-1 students who failed and fully repeated the M-1 year. To compare the groups upon admission, t-Tests comparing the Cognitive Index of students and MCAT scores from both groups were performed. Performance of the two groups after matriculation was also analyzed. Results Decompressed students were 2.1 times more likely to graduate. Decompressed students were 2.5 times more likely to pass USMLE Step 1 on the first attempt than the repeat students. In addition, 46% of those in the decompressed group completed the program in five years compared to 18% of the repeat group. Conclusion Medical students who decompress their M-1 year prior to M-1 year failure outperform those who fail their first year and then repeat it. These findings indicate the need for careful monitoring of M-1 student performance and early intervention and counseling of struggling students.

  11. Elastin-derived peptides promote abdominal aortic aneurysm formation by modulating M1/M2 macrophage polarization1

    Science.gov (United States)

    Dale, Matthew A; Xiong, Wanfen; Carson, Jeffrey S; Suh, Melissa K; Karpisek, Andrew D.; Meisinger, Trevor M.; Casale, George P.; Baxter, B. Timothy

    2016-01-01

    Abdominal aortic aneurysm (AAA) is a dynamic vascular disease characterized by inflammatory cell invasion and extracellular matrix (ECM) degradation. Damage to elastin in the ECM results in release of elastin-derived peptides (EDPs), which are chemotactic for inflammatory cells such as monocytes. Their effect on macrophage polarization is less well known. Pro-inflammatory M1 macrophages initially are recruited to sites of injury but, if their effects are prolonged, they can lead to chronic inflammation that prevents normal tissue repair. Conversely, anti-inflammatory M2 macrophages reduce inflammation and aid in wound healing. Thus, a proper M1/M2 ratio is vital for tissue homeostasis. AAA tissue reveals a high M1/M2 ratio where pro-inflammatory cells and their associated markers dominate. In the present study, in vitro treatment of bone marrow-derived macrophages with EDPs induced M1 macrophage polarization. By using C57Bl/6 mice, antibody-mediated neutralization of EDPs reduced aortic dilation, matrix metalloproteinase activity, and pro-inflammatory cytokine expression at early and late time points after aneurysm induction. Furthermore, direct manipulation of the M1/M2 balance altered aortic dilation. Injection of M2 polarized macrophages reduced aortic dilation after aneurysm induction. EDPs promoted a pro-inflammatory environment in aortic tissue by inducing M1 polarization and neutralization of EDPs attenuated aortic dilation. The M1/M2 imbalance is vital to aneurysm formation. PMID:27183603

  12. Cytosolic Pellino-1-Mediated K63-Linked Ubiquitination of IRF5 in M1 Macrophages Regulates Glucose Intolerance in Obesity

    Directory of Open Access Journals (Sweden)

    Donghyun Kim

    2017-07-01

    Full Text Available IRF5 is a signature transcription factor that induces M1 macrophage polarization. However, little is known regarding cytosolic proteins that induce IRF5 activation for M1 polarization. Here, we report the interaction between ubiquitin E3 ligase Pellino-1 and IRF5 in the cytoplasm, which increased nuclear translocation of IRF5 by K63-linked ubiquitination in human and mouse M1 macrophages. LPS and/or IFN-γ increased Pellino-1 expression, and M1 polarization was attenuated in Pellino-1-deficient macrophages in vitro and in vivo. Defective M1 polarization in Pellino-1-deficient macrophages improved glucose intolerance in mice fed a high-fat diet. Furthermore, macrophages in adipose tissues from obese humans exhibited increased Pellino-1 expression and IRF5 nuclear translocation compared with nonobese subjects, and these changes are associated with insulin resistance index. This study demonstrates that cytosolic Pellino-1-mediated K63-linked ubiquitination of IRF5 in M1 macrophages regulates glucose intolerance in obesity, suggesting a cytosolic mediator function of Pellino-1 in TLR4/IFN-γ receptor-IRF5 axis during M1 polarization.

  13. BION-M 1: First continuous blood pressure monitoring in mice during a 30-day spaceflight

    Science.gov (United States)

    Andreev-Andrievskiy, Alexander; Popova, Anfisa; Lloret, Jean-Christophe; Aubry, Patrick; Borovik, Anatoliy; Tsvirkun, Daria; Vinogradova, Olga; Ilyin, Eugeniy; Gauquelin-Koch, Guillemette; Gharib, Claude; Custaud, Marc-Antoine

    2017-05-01

    Animals are an essential component of space exploration and have been used to demonstrate that weightlessness does not disrupt essential physiological functions. They can also contribute to space research as models of weightlessness-induced changes in humans. Animal research was an integral component of the 30-day automated Russian biosatellite Bion-M 1 space mission. The aim of the hemodynamic experiment was to estimate cardiovascular function in mice, a species roughly 3000 times smaller than humans, during prolonged spaceflight and post-flight recovery, particularly, to investigate if mice display signs of cardiovascular deconditioning. For the first time, heart rate (HR) and blood pressure (BP) were continuously monitored using implantable telemetry during spaceflight and recovery. Decreased HR and unchanged BP were observed during launch, whereas both HR and BP dropped dramatically during descent. During spaceflight, BP did not change from pre-flight values. However, HR increased, particularly during periods of activity. HR remained elevated after spaceflight and was accompanied by increased levels of exercise-induced tachycardia. Loss of three of the five mice during the flight as a result of the hardware malfunction (unrelated to the telemetry system) and thus the limited sample number constitute the major limitation of the study. For the first time BP and HR were continuously monitored in mice during the 30-day spaceflight and 7-days of post-flight recovery. Cardiovascular deconditioning in these tiny quadruped mammals was reminiscent of that in humans. Therefore, the loss of hydrostatic pressure in space, which is thought to be the initiating event for human cardiovascular adaptation in microgravity, might be of less importance than other physiological mechanisms. Further experiments with larger number of mice are needed to confirm these findings.

  14. Wingspan stent for symptomatic M1 stenosis of middle cerebral artery

    International Nuclear Information System (INIS)

    Guo Xinbin; Ma Nan; Hu Xiaobo; Guan Sheng; Fan Yimu

    2011-01-01

    Objective: Stent placement for intracranial atherosclerotic stenosis has become an alternative treatment technique; however, stent placement for middle cerebral artery (MCA) stenosis remains a technical and clinical challenge. Our purpose was to assess the safety and feasibility of Wingspan stent for patients with symptomatic M1 stenosis, and its initial effect on prevention of ischemic events. Methods: Fifty-three cases with recurrent symptomatic MCA stenosis resistant to medical therapy treated by self-expanding stent were reviewed retrospectively (average 58 ± 18.5 years old, 19 women). All patients underwent angioplasty and stenting with the Gateway balloon–Wingspan stent system, and advised follow-up with DSA or TCD at 6th month. Results: Patients had an average stenosis ratio of 76.5 ± 15.4% prior to the treatment. Of the 53 patients, the technical success rate was 98.1% as a whole (52/53). The mean degree of stenosis reduced from (76.5 ± 15.4)% to (18.2 ± 11.3)%. Complications associated with the procedure include subarachnoid hemorrhage (1.89%) and occlusion (3.78%) occurred. During a follow-up of 6 months, there was no recurrence of transient ischemic attack or stroke in 52 cases with successful stenting. Cerebral hemodynamics of MCA using transcranial Doppler monitoring were at normal level (<120 cm/s) in 41 follow-up patients. The follow up angiography at 6 month post-procedure was conducted in 32 patients and showed good patency in stented vessels. Conclusions: Wingspan stent for symptomatic stenosis of middle cerebral artery is a safe and feasible procedure. It improves clinical outcome in the intermediate follow up, but its long-term effect remains to be further evaluated.

  15. Lactobacillus kefiranofaciens M1 isolated from milk kefir grains ameliorates experimental colitis in vitro and in vivo.

    Science.gov (United States)

    Chen, Y P; Hsiao, P J; Hong, W S; Dai, T Y; Chen, M J

    2012-01-01

    Lactobacillus kefiranofaciens M1, isolated from and identified in Taiwanese milk kefir grain, has demonstrated immune-modulating activity. In the present study, we further investigated the effects of Lb. kefiranofaciens M1 on intestinal epithelial cells in vitro and on dextran sodium sulfate (DSS)-induced colitis in vivo. The possible mechanisms regarding the cytokine products and intestinal epithelial barrier restoration as well as the putative receptor for the protective effects of Lb. kefiranofaciens M1 were investigated. In vitro results indicated that Lb. kefiranofaciens M1 could strengthen the epithelial barrier function in vitro by increasing the transepithelial electrical resistance (TEER) and significantly upregulated the level of the chemokine CCL-20 at both the apical and basolateral sites. The in vivo effects of Lb. kefiranofaciens M1 on the regulation of intestinal physiology indicate that this strain could ameliorate DSS-induced colitis with a significant attenuation of the bleeding score and colon length shortening. Production of proinflammatory cytokines was decreased and that of the antiinflammatory cytokine IL-10 was increased in the DSS-treated mice given Lb. kefiranofaciens M1. The putative receptor for the protective effects of Lb. kefiranofaciens M1 was toll-like receptor 2 (TLR2), which was involved in probiotic-induced cytokine production in vitro and in attenuation of the bleeding score and colon length shortening in vivo. In this study, the kefir lactobacillus Lb. kefiranofaciens M1 clearly demonstrated an anticolitis effect. Based on these results, Lb. kefiranofaciens M1 has the potential to be applied in fermented dairy products as an alternative therapy for intestinal disorders. Copyright © 2012 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  16. Endothelial and Smooth Muscle Cell Interaction via FoxM1 Signaling Mediates Vascular Remodeling and Pulmonary Hypertension.

    Science.gov (United States)

    Dai, Zhiyu; Zhu, Maggie M; Peng, Yi; Jin, Hua; Machireddy, Narsa; Qian, Zhijian; Zhang, Xianming; Zhao, You-Yang

    2018-04-17

    Angioproliferative vasculopathy is a hallmark of pulmonary arterial hypertension (PAH). However, little is known how endothelial cell (EC) and smooth muscle cell (SMC) crosstalk regulates the angioproliferative vascular remodeling. We aimed to investigate the role of EC and SMC interaction and underlying signaling pathways in PH development. SMC-specific Foxm1 or Cxcr4 knockout mice, EC-specific Foxm1 or Egln1 knockout mice, as well as EC-specific Egln1/Cxcl12 double knockout mice were used to assess the role of FoxM1 on SMC proliferation and PH. Lung tissues and cells from PAH patients were employed to validate clinical relevance. FoxM1 inhibitor Thiostrepton was used in Sugen 5416/hypoxia- and monocrotaline-challenged rats. FoxM1 expression was markedly upregulated in lungs and pulmonary arterial SMCs of idiopathic PAH patients and 4 discrete PH rodent models. Mice with SMC- (but not EC-) specific deletion of Foxm1 were protected from hypoxia- or Sugen 5416/hypoxia-induced PH. The upregulation of FoxM1 in SMCs induced by multiple EC-derived factors (PDGF-B, CXCL12, ET-1 and MIF) mediated SMC proliferation. Genetic deletion of endothelial Cxcl12 in Egln1Tie2Cre mice or loss of its cognate receptor Cxcr4 in SMCs in hypoxia-treated mice inhibited FoxM1 expression, SMC proliferation and PH. Accordingly, pharmacological inhibition of FoxM1 inhibited severe PH in both Sugen 5416/hypoxia and monocrotaline-challenged rats. Multiple factors derived from dysfunctional ECs induced FoxM1 expression in SMCs and activated FoxM1-dependent SMC proliferation which contributes to pulmonary vascular remodeling and PH. Thus, targeting FoxM1 signaling represents a novel strategy for treatment of IPAH.

  17. E2,M1 multipole mixing ratios in even--even nuclei, A greater than or equal to 152

    International Nuclear Information System (INIS)

    Krane, K.S.

    1975-01-01

    A survey is presented of E2,M1 mixing ratios of gamma-ray transitions in even-even nuclei with mass numbers A greater than or equal to 152. Angular distribution and correlation data from the literature are analyzed in terms of a consistent choice of the phase relationship between the E2 and M1 matrix elements. The cutoff date for the literature was June 1975. Based on an average of the experimental results from the literature, a recommended value of the E2,M1 mixing ratio for each transition is included

  18. Modulation of the ribonucleotide reductase M1-gemcitabine interaction in vivo by N-ethylmaleimide

    Energy Technology Data Exchange (ETDEWEB)

    Chen, Zhengming; Zhou, Jun; Zhang, Yingtao [Developmental Therapeutics Program, Karmanos Cancer Institute, Detroit, MI (United States); Bepler, Gerold, E-mail: beplerg@karmanos.org [Developmental Therapeutics Program, Karmanos Cancer Institute, Detroit, MI (United States)

    2011-09-23

    Highlights: {yields} Gemcitabine induces a RRM1 conformational change in tumor cell lines and xenografts. {yields} The 110 kDa RRM1 is unique to gemcitabine interaction among 12 cytotoxic agents. {yields} The 110 kDa RRM1 can be stabilized by the thiol alkylator N-ethylmaleimide. {yields} C218A, C429A, and E431A mutations in RRM1 abolished the conformational change. {yields} The 110 kDa RRM1 may be a specific biomarker of gemcitabine's therapeutic efficacy. -- Abstract: Ribonucleotide reductase M1 (RRM1) is the regulatory subunit of the holoenzyme that catalyzes the conversion of ribonucleotides to 2'-deoxyribonucleotides. Its function is indispensible in cell proliferation and DNA repair. It also serves as a biomarker of therapeutic efficacy of the antimetabolite drug gemcitabine (2',2'-difluoro-2'-deoxycytidine) in various malignancies. However, a mechanistic explanation remains to be determined. This study investigated how the alkylating agent N-ethylmaleimide (NEM) interacts with the inhibitory activity of gemcitabine on its target protein RRM1 in vivo. We found, when cells were treated with gemcitabine in the presence of NEM, a novel 110 kDa band, along with the 90 kDa native RRM1 band, appeared in immunoblots. This 110 kDa band was identified as RRM1 by mass spectrometry (LC-MS/MS) and represented a conformational change resulting from covalent labeling by gemcitabine. It is specific to gemcitabine/NEM, among 11 other chemotherapy drugs tested. It was also detectable in human tumor xenografts in mice treated with gemcitabine. Among mutations of seven residues essential for RRM1 function, C218A, C429A, and E431A abolished the conformational change, while N427A, C787A, and C790A diminished it. C444A was unique since it was able to alter the conformation even in absence of gemcitabine treatment. We conclude that the thiol alkylator NEM can stabilize the gemcitabine-induced conformational change of RRM1, and this stabilized RRM1

  19. Modulation of the ribonucleotide reductase M1-gemcitabine interaction in vivo by N-ethylmaleimide

    International Nuclear Information System (INIS)

    Chen, Zhengming; Zhou, Jun; Zhang, Yingtao; Bepler, Gerold

    2011-01-01

    Highlights: → Gemcitabine induces a RRM1 conformational change in tumor cell lines and xenografts. → The 110 kDa RRM1 is unique to gemcitabine interaction among 12 cytotoxic agents. → The 110 kDa RRM1 can be stabilized by the thiol alkylator N-ethylmaleimide. → C218A, C429A, and E431A mutations in RRM1 abolished the conformational change. → The 110 kDa RRM1 may be a specific biomarker of gemcitabine's therapeutic efficacy. -- Abstract: Ribonucleotide reductase M1 (RRM1) is the regulatory subunit of the holoenzyme that catalyzes the conversion of ribonucleotides to 2'-deoxyribonucleotides. Its function is indispensible in cell proliferation and DNA repair. It also serves as a biomarker of therapeutic efficacy of the antimetabolite drug gemcitabine (2',2'-difluoro-2'-deoxycytidine) in various malignancies. However, a mechanistic explanation remains to be determined. This study investigated how the alkylating agent N-ethylmaleimide (NEM) interacts with the inhibitory activity of gemcitabine on its target protein RRM1 in vivo. We found, when cells were treated with gemcitabine in the presence of NEM, a novel 110 kDa band, along with the 90 kDa native RRM1 band, appeared in immunoblots. This 110 kDa band was identified as RRM1 by mass spectrometry (LC-MS/MS) and represented a conformational change resulting from covalent labeling by gemcitabine. It is specific to gemcitabine/NEM, among 11 other chemotherapy drugs tested. It was also detectable in human tumor xenografts in mice treated with gemcitabine. Among mutations of seven residues essential for RRM1 function, C218A, C429A, and E431A abolished the conformational change, while N427A, C787A, and C790A diminished it. C444A was unique since it was able to alter the conformation even in absence of gemcitabine treatment. We conclude that the thiol alkylator NEM can stabilize the gemcitabine-induced conformational change of RRM1, and this stabilized RRM1 conformation has the potential to serve as a specific

  20. detection of aflatoxin M1 contamination in milk for Syrian market using ELISA

    International Nuclear Information System (INIS)

    Ghanem, I.; Orfi, M.

    2008-01-01

    Aflatoxin M1 (AFM1) is the hydroxylated metabolite of a biotransformation process of Aflatoxin B1 (AFB1) which is produced in food and feed by the fungi Aspergillus flavus and A. paraciticus. AFM1 has been shown to be excreted in milk following exposure to AFB1 contaminated feed. Since milk is consumed in large quantities by human populations, particularly among infants and young children the occurrence of AFM1 in this product is constitutes and health hazard since it is carcinogenic and has been listed as Class 2B carcinogen. The occurrence of AFM1 in milk samples from the Syrian market was investigated by the competitive ELISA technique. A total of 126 samples consisting of fresh cow milk (74), locally processed pasteurized cow milk (10), sheep milk (23), goat milk (11) and powdered milk and infant formula (8) showed that the incidence of contamination, i.e. above the detection limit of the ELISA assay, was 80%. 18% of the tested samples contained higher than the acceptable level of AFM1 adopted in Syria, which is 200 ng/kg; whereas, 17% and 54% of all tested samples contained AFM1 higher than the acceptable level in the US, (500 ng/kg) and in the European Union (50 ng/kg), respectively. The range of contamination with AFM1 was higher in cow milk samples than in sheep milk and goat milk samples. 30% of the analyzed cow fresh milk samples contained levels of AFM1 exceeding that of the European Communities (Codex Alimentarius) recommended limits (50 ng/l); whereas, 13% of the analyzed sheep milk samples (23) exceeded the latter limit, and only 9% of the analyzed goat milk samples exceeded same limit. Pasteurized milk, which is collected from various locations, showed particularly high level of contamination, with 80% and 50% of tested samples showing levels of contamination higher than the European and US acceptable levels, respectively. Powdered milk and infant formula, which are imported and only dispensed locally, were free of contamination. The above result

  1. Bion M1. Peculiarities of life activities of microbes in 30-day spaceflight

    Science.gov (United States)

    Viacheslav, Ilyin; Korshunov, Denis; Morozova, Julia; Voeikova, Tatiana; Tyaglov, Boris; Novikova, Liudmila; Krestyanova, Irina; Emelyanova, Lydia

    The aim of this work was to analyze the influence of space flight factors ( SFF) to microorganism strains , exposed inside unmanned spacecraft Bion M-1 during the 30- day space flight. Objectives of the work - the study of the influence of the SFF exchange chromosomal DNA in crosses microorganisms of the genus Streptomyces; the level of spontaneous phage induction of lysogenic strains fS31 from Streptomyces lividans 66 and Streptomyces coelicolor A3 ( 2 ) on the biosynthesis of the antibiotic tylosin strain of Streptomyces fradiae; survival electrogenic bacteria Shewanella oneidensis MR- 1 is used in the microbial fuel cell As a result of this work it was found that the SFF affect the exchange of chromosomal DNA by crossing strains of Streptomyces. Was detected polarity crossing , expressed in an advantageous contribution chromosome fragment of one of the parent strains in recombinant offspring. This fact may indicate a more prolonged exposure of cells in microgravity and , as a consequence, the transfer of longer fragments of chromosomal DNA This feature is the transfer of genetic material in microgravity could lead to wider dissemination and horizontal transfer of chromosomal and plasmid DNA of symbiotic microflora astronauts and other strains present in the spacecraft. It was shown no effect on the frequency of recombination PCF and the level of mutation model reversion of auxotrophic markers to prototrophy It was demonstrated that PCF increase the level of induction of cell actinophage fS31 lysogenic strain of S. lividans 66, but did not affect the level of induction of this phage cells S. coelicolor A3 ( 2). It is shown that the lower the level of synthesis PCF antibiotic aktinorodina (actinorhodin) in lysogenic strain S. coelicolor A3 ( 2). 66 Strains of S. lividans and S. coelicolor A3 ( 2 ) can be used as a biosensor for studying the effect on microorganisms PCF It is shown that the effect of the PCF reduces synthesis of tylosin and desmicosyn S. fradiae at

  2. Effect of 60Co gamma radiation on the performance of two soybean varieties in M1 and M2 generations

    International Nuclear Information System (INIS)

    Miah, M.A.; Rahman, L.

    1982-01-01

    Seed of two soybean varieties Bragg and Improved Pelican were treated with gamma-rays at 0, 11, 29, 47 and 65 Kr doses. Percentage of seedling emergence in both varieties in M 1 generation was not so seriously affected as in M 1 generation. The plant height of Bragg after one month of sowing was less influenced than Improved Pelican. Plant height of both the varieties decreased with increase in radiation doses; except 11 Kr in Bragg in both generations. Similar results were also obtained in plant height at harvest except that Improved Pelican in M 1 generation produced taller plants at 29 Kr than at 11 Kr level. Days required to harvest increased at higher doses in comparison to control, except 11 Kr for Improved Pelican and 29 Kr for Bragg in M 1 generation. (author)

  3. Evaluation of different glycoforms of honeybee venom major allergen phospholipase A2 (Api m 1) produced in insect cells

    DEFF Research Database (Denmark)

    Blank, Simon; Seismann, Henning; Plum, Melanie

    2011-01-01

    Allergic reactions to hymenoptera stings are one of the major reasons for IgE-mediated anaphylaxis. However, proper diagnosis using venom extracts is severely affected by molecular cross-reactivity. In this study recombinant honeybee venom major allergen phospholipase A2 (Api m 1) was produced......-derived recombinant Api m 1 with defined CCD phenotypes might provide further insights into hymenoptera venom IgE reactivities and contribute to an improved diagnosis of hymenoptera venom allergy....

  4. A novel M1 PAM VU0486846 exerts efficacy in cognition models without displaying agonist activity or cholinergic toxicity.

    Science.gov (United States)

    Rook, Jerri M; Bertron, Jeanette L; Cho, Hyekyung P; Garcia-Barrantes, Pedro M; Moran, Sean P; Maksymetz, James T; Nance, Kellie D; Dickerson, Jonathan W; Remke, Daniel H; Chang, Sichen; Harp, Joel; Blobaum, Anna L; Niswender, Colleen M; Jones, Carrie K; Stauffer, Shaun R; Conn, P Jeffrey; Lindsley, Craig W

    2018-04-27

    Selective activation of the M1 subtype of muscarinic acetylcholine receptor, via positive allosteric modulation (PAM), is an exciting strategy to improve cognition in schizophrenia and Alzheimer's disease patients. However, highly potent M1 ago-PAMs, such as MK-7622, PF-06764427, and PF-06827443, can engender excessive activation of M1, leading to agonist actions in the prefrontal cortex (PFC) that impairs cognitive function, induces behavioral convulsions, and results in other classic cholinergic adverse events (AEs). Here, we report a fundamentally new and highly selective M1 PAM, VU0486846. VU0486846 possesses only weak agonist activity in M1-expressing cell lines with high receptor reserve and is devoid of agonist actions in the PFC, unlike previously reported ago-PAMs MK-7622, PF-06764427 and PF-06827443. Moreover, VU0486846 shows no interaction with antagonist binding at the orthosteric acetylcholine (ACh) site (e.g., neither bitopic nor displaying negative cooperativity with [3H]-NMS binding at theorthosteric site), no seizure liability at high brain exposures, and no cholinergic AEs. However, as opposed to ago-PAMs, VU0486846 produces robust efficacy in the novel object recognition model of cognitive function. Importantly, we show for the first time that an M1 PAM can reverse the cognitive deficits induced by atypical antipsychotics, such as risperidone. These findings further strengthen the argument that compounds with modest in vitro M1 PAM activity (EC50s > 100 nM) and pure-PAM activity in native tissues display robust pro-cognitive efficacy without AEs mediated by excessive activation of M1. Overall, the combination of compound assessment with recombinant in vitro assays (mindful of receptor reserve), native tissue systems (PFC), and phenotypic screens (behavioral convulsions) is essential to fully understand and evaluate lead compounds and enhance success in clinical development.

  5. Effect of heat-inactivated kefir-isolated Lactobacillus kefiranofaciens M1 on preventing an allergic airway response in mice.

    Science.gov (United States)

    Hong, Wei-Sheng; Chen, Yen-Po; Dai, Ting-Yeu; Huang, I-Nung; Chen, Ming-Ju

    2011-08-24

    In this study, we assessed the anti-asthmatic effects of heat-inactivated Lactobacillus kefiranofaciens M1 (HI-M1) and its fermented milk using different feeding procedures and at various dosage levels. The possible mechanisms whereby HI-M1 has anti-allergic asthmatic effects were also evaluated. Ovalbumin (OVA)-allergic asthma mice that have been orally administrated the HI-M1 samples showed strong inhibition of production of T helper cell (Th) 2 cytokines, pro-inflammatory cytokines, and Th17 cytokines in splenocytes and bronchoalveolar fluid compared to control mice. An increase in regulatory T cell population in splenocytes in the allergic asthma mice after oral administration of H1-M1 was also observed. In addition, all of the features of the asthmatic phenotype, including specific IgE production, airway inflammation, and development of airway hyperresponsiveness, were depressed in a dose-dependent manner by treatment. These findings support the possibility that oral feeding of H1-M1 may be an effective way of alleviating asthmatic symptoms in humans.

  6. Selective replication of oncolytic virus M1 results in a bystander killing effect that is potentiated by Smac mimetics.

    Science.gov (United States)

    Cai, Jing; Lin, Yuan; Zhang, Haipeng; Liang, Jiankai; Tan, Yaqian; Cavenee, Webster K; Yan, Guangmei

    2017-06-27

    Oncolytic virotherapy is a treatment modality that uses native or genetically modified viruses that selectively replicate in and kill tumor cells. Viruses represent a type of pathogen-associated molecular pattern and thereby induce the up-regulation of dozens of cytokines via activating the host innate immune system. Second mitochondria-derived activator of caspases (Smac) mimetic compounds (SMCs), which antagonize the function of inhibitor of apoptosis proteins (IAPs) and induce apoptosis, sensitize tumor cells to multiple cytokines. Therefore, we sought to determine whether SMCs sensitize tumor cells to cytokines induced by the oncolytic M1 virus, thus enhancing a bystander killing effect. Here, we report that SMCs potentiate the oncolytic effect of M1 in vitro, in vivo, and ex vivo. This strengthened oncolytic efficacy resulted from the enhanced bystander killing effect caused by the M1 virus via cytokine induction. Through a microarray analysis and subsequent validation using recombinant cytokines, we identified IL-8, IL-1A, and TRAIL as the key cytokines in the bystander killing effect. Furthermore, SMCs increased the replication of M1, and the accumulation of virus protein induced irreversible endoplasmic reticulum stress- and c-Jun N-terminal kinase-mediated apoptosis. Nevertheless, the combined treatment with M1 and SMCs had little effect on normal and human primary cells. Because SMCs selectively and significantly enhance the bystander killing effect and the replication of oncolytic virus M1 specifically in cancer cells, this combined treatment may represent a promising therapeutic strategy.

  7. Paeoniflorin inhibits cell growth and induces cell cycle arrest through inhibition of FoxM1 in colorectal cancer cells.

    Science.gov (United States)

    Yue, Meng; Li, Shiquan; Yan, Guoqiang; Li, Chenyao; Kang, Zhenhua

    2018-01-01

    Paeoniflorin (PF) exhibits tumor suppressive functions in a variety of human cancers. However, the function of PF and molecular mechanism in colorectal cancer are elusive. In the present study, we investigated whether PF could exert its antiproliferative activity, anti-migration, and anti-invasive function in colorectal cancer cells. We found that PF inhibited cell growth and induced apoptosis and blocked cell cycle progression in the G0/G1 phase in colorectal cancer cells. Moreover, we found that PF suppressed cell migration and invasion in colorectal cancer cells. FoxM1 has been reported to play an important oncogenic role in human cancers. We also determine whether PF inhibited the expression of FoxM1, leading to its anti-cancer activity. We found that PF treatment in colorectal cancer cells resulted in down-regulation of FoxM1. The rescue experiments showed that overexpression of FoxM1 abrogated the tumor suppressive function induced by PF treatment. Notably, depletion of FoxM1 promoted the anti-tumor activity of PF in colorectal cancer cells. Therefore, inhibition of FoxM1 could participate in the anti-tumor activity of PF in colorectal cancer cells.

  8. Effects of selective activation of M1 and M4 muscarinic receptors on object recognition memory performance in rats.

    Science.gov (United States)

    Galloway, Claire R; Lebois, Evan P; Shagarabi, Shezza L; Hernandez, Norma A; Manns, Joseph R

    2014-01-01

    Acetylcholine signaling through muscarinic receptors has been shown to benefit memory performance in some conditions, but pan-muscarinic activation also frequently leads to peripheral side effects. Drug therapies that selectively target M1 or M4 muscarinic receptors could potentially improve memory while minimizing side effects mediated by the other muscarinic receptor subtypes. The ability of three recently developed drugs that selectively activate M1 or M4 receptors to improve recognition memory was tested by giving Long-Evans rats subcutaneous injections of three different doses of the M1 agonist VU0364572, the M1 positive allosteric modulator BQCA or the M4 positive allosteric modulator VU0152100 before performing an object recognition memory task. VU0364572 at 0.1 mg/kg, BQCA at 1.0 mg/kg and VU0152100 at 3.0 and 30.0 mg/kg improved the memory performance of rats that performed poorly at baseline, yet the improvements in memory performance were the most statistically robust for VU0152100 at 3.0 mg/kg. The results suggested that selective M1 and M4 receptor activation each improved memory but that the likelihood of obtaining behavioral efficacy at a given dose might vary between subjects even in healthy groups depending on baseline performance. These results also highlighted the potential of drug therapies that selectively target M1 or M4 receptors to improve memory performance in individuals with impaired memory.

  9. Bioimaging of M1 cells using ceramic nanophosphors: Synthesis and toxicity assay of Y2O3 nanoparticles

    International Nuclear Information System (INIS)

    Venkatachalam, N; Soga, K; Tsuji, T; Okumura, Y; Fukuda, R

    2009-01-01

    Er 3+ doped Y 2 O 3 nanoparticles were synthesized by enzymatic and polymer-assisted homogeneous co-precipitation methods. Resultant particle size is about 30-40 nm with narrow size distribution whereas the particle size is smaller than those acquired by conventional homogeneous and alkali precipitation methods. The particles shows bright green (550 nm) and red (660 nm) upconversion (UC) as well as near infrared (NIR) fluorescence (1550 nm) under 980 nm excitation. Bioimaging of M1 cells using the nanoparticles were successfully attempted. It is observed that 0.5 mg/ml of nanoparticles is the nominal concentration for bioimaging of M1 cells under the physiological conditions. The cellular uptake of nanoparticles is evidenced from bright field, UC and NIR fluorescence images of live M1 cells. Our studies suggest that lower concentration of nanoparticles is sufficient for imaging when the particles are taken in the M1 cells and also the concentration can keep the cells alive. Further it was demonstrated that under the physiological conditions, Y 2 O 3 nanoparticles emit UC and NIR fluorescence in M1 cells even after the surface modification with PEG-b-PAAc polymer. Moreover, surface modified nanoparticles shows lower toxic effect in M1 cells while compare to bare nanoparticles.

  10. Increased Expression of FoxM1 Transcription Factor in Respiratory Epithelium Inhibits Lung Sacculation and Causes Clara Cell Hyperplasia

    Science.gov (United States)

    Wang, I-Ching; Zhang, Yufang; Snyder, Jonathan; Sutherland, Mardi J.; Burhans, Michael S.; Shannon, John M.; Park, Hyun Jung; Whitsett, Jeffrey A.; Kalinichenko, Vladimir V.

    2010-01-01

    Foxm1 is a member of the Forkhead Box (Fox) family of transcription factors. Foxm1 (previously called Foxm1b, HFH-11B, Trident, Win, or MPP2) is expressed in multiple cell types and plays important roles in cellular proliferation, differentiation and tumorigenesis. Genetic deletion of Foxm1 from mouse respiratory epithelium during initial stages of lung development inhibits lung maturation and causes respiratory failure after birth. However, the role of Foxm1 during postnatal lung morphogenesis remains unknown. In the present study, Foxm1 expression was detected in epithelial cells of conducting and peripheral airways and changing dynamically with lung maturation. To discern the biological role of Foxm1 in the prenatal and postnatal lung, a novel transgenic mouse line that expresses a constitutively active form of FoxM1 (FoxM1 N-terminal deletion mutant or FoxM1-ΔN) under the control of lung epithelial-specific SPC promoter was produced. Expression of the FoxM1-ΔN transgene during embryogenesis caused epithelial hyperplasia, inhibited lung sacculation and expression of the type II epithelial marker, pro-SPC. Expression of FoxM1-ΔN mutant during the postnatal period did not influence alveologenesis but caused focal airway hyperplasia and increased proliferation of Clara cells. Likewise, expression of FoxM1-ΔN mutant in conducting airways with Scgb1a1 promoter was sufficient to induce Clara cell hyperplasia. Furthermore, FoxM1-ΔN cooperated with activated K-Ras to induce lung tumor growth in vivo. Increased activity of Foxm1 altered lung sacculation, induced proliferation in the respiratory epithelium and accelerated lung tumor growth, indicating that precise regulation of Foxm1 is critical for normal lung morphogenesis and development of lung cancer. PMID:20816795

  11. Correlation of Acute M1 Middle Cerebral Artery Thrombus Location with Endovascular Treatment Success and Clinical Outcome.

    Science.gov (United States)

    Pavabvash, Seyedmehdi; Taleb, Shayandokht; Majidi, Shahram; Qureshi, Adnan I

    2017-01-01

    The location of the arterial occlusion can help with prognostication and treatment triage of acute stroke patients. We aimed to determine the effects of M1 distance-to-thrombus on angiographic recanalization success rate and clinical outcome following endovascular treatment of acute M1 occlusion. All acute ischemic stroke patients with M1 segment middle cerebral artery (MCA) occlusion on admission CT angiography (CTA) who underwent endovascular treatment were analyzed. The distance between thrombus origin and internal carotid artery (ICA) bifurcation was measured on admission CTA. The modified thrombolysis in cerebral infarction (mTICI) grades 2 b (>50% of distal branch filling) and 3 (complete) were considered as successful recanalization. Favorable outcome was defined by 3-month follow-up modified Rankin scale (mRs) score ≤2. Successful recanalization was achieved in 24 (71%) of 34 consecutive patients included in this study. The M1 distance-to-thrombus was shorter among patients with successful recanalization (5.4 ± 5.4 mm) versus those without (11.3 ± 7.6 mm, p = 0.015). The successful recanalization rate was higher among patients with M1 distance-to-thrombus ≤6 mm (odds ratio: 8, 95% confidence interval: 1.37-46.81, p = 0.023) compared with those with distance-to-thrombus >6 mm. There was no significant correlation between M1 distance-to-thrombus and 3-month mRs (rho: 0.131, p = 0.461); however, the distance-to-thrombus negatively correlated with admission National Institutes of Health Stroke Scale (NIHSS) scores (rho: -0.350, p=0.043). On the other hand, successful recanalization and admission NIHSS score were the only independent predictors of favorable outcome. Shorter distance of M1 thrombus from ICA bifurcation is associated with higher rate of successful recanalization following endovascular treatment.

  12. Correlation of Acute M1 Middle Cerebral Artery Thrombus Location with Endovascular Treatment Success and Clinical Outcome

    Science.gov (United States)

    Pavabvash, Seyedmehdi; Taleb, Shayandokht; Majidi, Shahram; Qureshi, Adnan I.

    2017-01-01

    Purpose The location of the arterial occlusion can help with prognostication and treatment triage of acute stroke patients. We aimed to determine the effects of M1 distance-to-thrombus on angiographic recanalization success rate and clinical outcome following endovascular treatment of acute M1 occlusion. Methods All acute ischemic stroke patients with M1 segment middle cerebral artery (MCA) occlusion on admission CT angiography (CTA) who underwent endovascular treatment were analyzed. The distance between thrombus origin and internal carotid artery (ICA) bifurcation was measured on admission CTA. The modified thrombolysis in cerebral infarction (mTICI) grades 2b (>50% of distal branch filling) and 3 (complete) were considered as successful recanalization. Favorable outcome was defined by 3-month follow-up modified Rankin scale (mRs) score ≤2. Results Successful recanalization was achieved in 24 (71%) of 34 consecutive patients included in this study. The M1 distance-to-thrombus was shorter among patients with successful recanalization (5.4 ± 5.4 mm) versus those without (11.3 ± 7.6 mm, p = 0.015). The successful recanalization rate was higher among patients with M1 distance-to-thrombus ≤6 mm (odds ratio: 8, 95% confidence interval: 1.37–46.81, p = 0.023) compared with those with distance-to-thrombus >6 mm. There was no significant correlation between M1 distance-to-thrombus and 3-month mRs (rho: 0.131, p = 0.461); however, the distance-to-thrombus negatively correlated with admission National Institutes of Health Stroke Scale (NIHSS) scores (rho: −0.350, p=0.043). On the other hand, successful recanalization and admission NIHSS score were the only independent predictors of favorable outcome. Conclusion Shorter distance of M1 thrombus from ICA bifurcation is associated with higher rate of successful recanalization following endovascular treatment. PMID:28243346

  13. A new and efficient culture method for porcine bone marrow-derived M1- and M2-polarized macrophages.

    Science.gov (United States)

    Gao, Jiye; Scheenstra, Maaike R; van Dijk, Albert; Veldhuizen, Edwin J A; Haagsman, Henk P

    2018-06-01

    Macrophages play an important role in the innate immune system as part of the mononuclear phagocyte system (MPS). They have a pro-inflammatory signature (M1-polarized macrophages) or anti-inflammatory signature (M2-polarized macrophages) based on expression of surface receptors and secretion of cytokines. However, very little is known about the culture of macrophages from pigs and more specific about the M1 and M2 polarization in vitro. Porcine monocytes or mononuclear bone marrow cells were used to culture M1- and M2-polarized macrophages in the presence of GM-CSF and M-CSF, respectively. Surface receptor expression was measured with flow cytometry and ELISA was used to quantify cytokine secretion in response to LPS and PAM 3 CSK 4 stimulation. Human monocyte-derived macrophages were used as control. Porcine M1- and M2-polarized macrophages were cultured best using porcine GM-CSF and murine M-CSF, respectively. Cultures from bone marrow cells resulted in a higher yield M1- and M2-polarized macrophages which were better comparable to human monocyte-derived macrophages than cultures from porcine monocytes. Porcine M1-polarized macrophages displayed the characteristic fried egg shape morphology, lower CD163 expression and low IL-10 production. Porcine M2-polarized macrophages contained the spindle-like morphology, higher CD163 expression and high IL-10 production. Porcine M1- and M2-polarized macrophages can be most efficiently cultured from mononuclear bone marrow cells using porcine GM-CSF and murine M-CSF. The new culture method facilitates more refined studies of porcine macrophages in vitro, important for both porcine and human health since pigs are increasingly used as model for translational research. Copyright © 2018 The Authors. Published by Elsevier B.V. All rights reserved.

  14. Overexpression of the polycystin-1 (PC-1) C-tail enhances sensitivity of M-1 cells to ouabain

    Science.gov (United States)

    Jansson, Kyle; Magenheimer, Brenda S.; Maser, Robin L.; Calvet, James P.; Blanco, Gustavo

    2014-01-01

    Cells derived from renal cysts of patients with autosomal dominant polycystic kidney disease (ADPKD) are abnormally sensitive to ouabain, responding to physiological ouabain concentrations with enhanced proliferation and increased forskolin-induced transepithelial fluid secretion. This requires activation of the epidermal growth factor receptor (EGFR), Src kinase, and the extracellular regulated kinases MEK and ERK. Here, we have determined if the ADPKD phenotype obtained in mouse cortical collecting duct cells by stable overexpression of the C-terminal domain of polycystin-1 (PC-1 C-tail) also elicits the ADPKD-like response to ouabain in the cells. M-1 C20 cells expressing the PC-1 C-tail, and M-1 C17 cells, lacking expression of this construct, were treated with physiological concentrations of ouabain, and cell proliferation, activation of the EGFR-Src-MEK-ERK pathway, forskolin-induced transepithelial Cl− secretion, and the sensitivity of the Na,K-ATPase to ouabain were explored. M-1 C20 cells responded to ouabain with increased cell proliferation and ERK phosphorylation. Ouabain also augmented forskolin-induced and cystic fibrosis transmembrane conductance regulator (CFTR)-mediated apical secretion of Cl− in M-1 C20 cells. These effects required activation of EGFR, Src and MEK. In contrast, ouabain had no significant effects on M-1 C17 cells. Interestingly, approximately 20 % of the Na,K-ATPase from M-1 C20 cells presented an abnormally increased sensitivity to ouabain. Overexpression of PC-1 C-tail in M-1 C20 cells is associated with a ouabain sensitive phenotype and an increased ability of the cells to proliferate and secrete anions upon ouabain stimulation. This phenotype mimics the ouabain sensitivity of ADPKD cells and may help promote their cystogenic potential. PMID:23784065

  15. Differential S1P Receptor Profiles on M1- and M2-Polarized Macrophages Affect Macrophage Cytokine Production and Migration.

    Science.gov (United States)

    Müller, Jan; von Bernstorff, Wolfram; Heidecke, Claus-Dieter; Schulze, Tobias

    2017-01-01

    Introduction . Macrophages are key players in complex biological processes. In response to environmental signals, macrophages undergo polarization towards a proinflammatory (M1) or anti-inflammatory (M2) phenotype. Sphingosine 1-phosphate (S1P) is a bioactive lysophospholipid that acts via 5 G-protein coupled receptors (S1P 1-5 ) in order to influence a broad spectrum of biological processes. This study assesses S1P receptor expression on macrophages before and after M1 and M2 polarization and performs a comparative analysis of S1P signalling in the two activational states of macrophages. Methods . Bone marrow derived macrophages (BMDM) from C57 BL/6 mice were cultured under either M1- or M2-polarizing conditions. S1P-receptor expression was determined by quantitative RT-PCR. Influence of S1P on macrophage activation, migration, phagocytosis, and cytokine secretion was assessed in vitro. Results . All 5 S1P receptor subclasses were expressed in macrophages. Culture under both M1- and M2-polarizing conditions led to significant downregulation of S1P 1 . In contrast, M1-polarized macrophages significantly downregulated S1P 4 . The expression of the remaining three S1P receptors did not change. S1P increased expression of iNOS under M2-polarizing conditions. Furthermore, S1P induced chemotaxis in M1 macrophages and changed cytokine production in M2 macrophages. Phagocytosis was not affected by S1P-signalling. Discussion . The expression of different specific S1P receptor profiles may provide a possibility to selectively influence M1- or M2-polarized macrophages.

  16. M1 and M2 macrophages derived from THP-1 cells differentially modulate the response of cancer cells to etoposide

    International Nuclear Information System (INIS)

    Genin, Marie; Clement, Francois; Fattaccioli, Antoine; Raes, Martine; Michiels, Carine

    2015-01-01

    Tumor associated macrophages (TAMs) are present in high density in solid tumors. TAMs share many characteristics with alternatively activated macrophages, also called M2. They have been shown to favor tumor development and a role in chemoresistance has also been suggested. Here, we investigated the effects of M2 in comparison to M1 macrophages on cancer cell sensitivity to etoposide. We set up a model of macrophage polarization, starting from THP-1 monocytes differentiated into macrophages using PMA (Phorbol 12-myristate 13-acetate). Once differentiated (M0 macrophages), they were incubated with IL-4 and IL-13 in order to obtain M2 polarized macrophages or with IFN-gamma and LPS for classical macrophage activation (M1). To mimic the communication between cancer cells and TAMs, M0, M1 or M2 macrophages and HepG2 or A549 cancer cells were co-cultured during respectively 16 (HepG2) or 24 (A549) hours, before etoposide exposure for 24 (HepG2) or 16 (A549) hours. After the incubation, the impact of etoposide on macrophage polarization was studied and cancer cell apoptosis was assessed by western-blot for cleaved caspase-3 and cleaved PARP-1 protein, caspase activity assay and FACS analysis of Annexin V and PI staining. mRNA and protein expression of M1 and M2 markers confirmed the polarization of THP-1-derived macrophages, which provide a new, easy and well-characterized model of polarized human macrophages. Etoposide-induced cancer cell apoptosis was markedly reduced in the presence of THP-1 M2 macrophages, while apoptosis was increased in cells co-cultured with M1 macrophages. On the other hand, etoposide did not influence M1 or M2 polarization. These results evidence for the first time a clear protective effect of M2 on the contrary to M1 macrophages on etoposide-induced cancer cell apoptosis

  17. Three-fold increase of M1 strength in 40Ar at 10 MeV excitation energy

    Science.gov (United States)

    Tornow, Werner; Finch, Sean; Krishichayan, Fnu; Tonchev, Anton

    2017-09-01

    We reexamined the excitation energy region of 40Ar around 9.8 MeV with the goal of determining the known M1 strength located at 9.76 MeV more accurately. The physics motivation was based on the fact that i) the neutrino-nucleus interaction cross section is proportional to the M1 strength of a nucleus, ii) DUNE, the Deep Underground Neutrino Experiment at SURF will be using liquid argon as detector medium, iii) the energy spectrum of supernova neutrinos is peaked at approximately 10 MeV. Mono-energetic and linearly polarized photons of 9.88 MeV were produced via Compton backscattering of 548 nm FEL photons from 543 MeV electrons at the High-Intensity γ-ray Source (HI γS) facility at TUNL. The 1.25 cm diameter photon beam with energy spread of 300 keV (FWHM) interacted with argon gas contained in a high-pressure cell. The cell was viewed with HPGe detectors placed at 90o relative to the incident photon beam in the horizontal and vertical planes to distinguish between E1 and M1 de-excitation γ-rays. Our re-measurement provided an increase in M1 strength by a factor of approximately 3, mostly due to the discovery that the known level in 40Ar at 9.84 MeV is of M1 character and not of E1 character, as previously thought. In addition to the already known M1 state at 9.76 MeV, we observed weaker M1 states at 9.70, 9.81, 9.87, and 9.89 MeV.

  18. Theoretical descriptions of novel triplet germylenes M1-Ge-M2-M3 (M1 = H, Li, Na, K; M2 = Be, Mg, Ca; M3 = H, F, Cl, Br).

    Science.gov (United States)

    Kassaee, Mohamad Zaman; Ashenagar, Samaneh

    2018-02-06

    In a quest to identify new ground-state triplet germylenes, the stabilities (singlet-triplet energy differences, ΔE S-T ) of 96 singlet (s) and triplet (t) M 1 -Ge-M 2 -M 3 species were compared and contrasted at the B3LYP/6-311++G**, QCISD(T)/6-311++G**, and CCSD(T)/6-311++G** levels of theory (M 1  = H, Li, Na, K; M 2  = Be, Mg, Ca; M 3  = H, F, Cl, Br). Interestingly, F-substituent triplet germylenes (M 3  = F) appear to be more stable and linear than the corresponding Cl- or Br-substituent triplet germylenes (M 3  = Cl or Br). Triplets with M 1  = K (i.e., the K-Ge-M 2 -M 3 series) seem to be more stable than the corresponding triplets with M 1  = H, Li, or Na. This can be attributed to the higher electropositivity of potassium. Triplet species with M 3  = Cl behave similarly to those with M 3  = Br. Conversely, triplets with M 3  = H show similar stabilities and linearities to those with M 3  = F. Singlet species of formulae K-Ge-Ca-Cl and K-Ge-Ca-Br form unexpected cyclic structures. Finally, the triplet germylenes M 1 -Ge-M 2 -M 3 become more stable as the electropositivities of the α-substituents (M 1 and M 2 ) and the electronegativity of the β-substituent (M 3 ) increase.

  19. Quinoline-based clioquinol and nitroxoline exhibit anticancer activity inducing FoxM1 inhibition in cholangiocarcinoma cells

    Directory of Open Access Journals (Sweden)

    Chan-on W

    2015-04-01

    Full Text Available Waraporn Chan-on,1 Nguyen Thi Bich Huyen,2 Napat Songtawee,3 Wilasinee Suwanjang,1 Supaluk Prachayasittikul,3 Virapong Prachayasittikul2 1Center for Research and Innovation, 2Department of Clinical Microbiology and Applied Technology, 3Center of Data Mining and Biomedical Informatics, Faculty of Medical Technology, Mahidol University, Bangkok, Thailand Purpose: Fork head box M1 (FoxM1 is an oncogenic transcription factor frequently elevated in numerous cancers, including cholangiocarcinoma (CCA. A growing body of evidence documents its diverse functions contributing to tumorigenesis and cancer progression. As such, discovery of agents that can target FoxM1 would be valuable for the treatment of CCA. The quinoline-based compounds, namely clioquinol (CQ and nitroxoline (NQ, represent a new class of anticancer drug. However, their efficacy and underlying mechanisms have not been elucidated in CCA. In this study, anticancer activities and inhibitory effects of CQ and NQ on FoxM1 signaling were explored using CCA cells.Methods: The effects of CQ and NQ on cell viability and proliferation were evaluated using the colorimetric 3-(4,5-dimethylthiazol-2yl-5-(3-carboxymethoxyphenyl-(4-sulfophenyl-2H-tetrazolium (MTS assay. Colony formation and cell migration affected by CQ and NQ were investigated using a clonogenic and a wound healing assay, respectively. To demonstrate the agents’ effects on FoxM1 signaling, expression levels of the target genes were quantitatively determined using real-time polymerase chain reaction.Results: CQ and NQ significantly inhibited cell survival of HuCCT1 and Huh28 in a dose- and a time-dependent fashion. Further investigations using the rapidly proliferating HuCCT1 cells revealed significant suppression of cell proliferation and colony formation induced by low doses of the compounds. Treatment of CQ and NQ repressed expression of cyclin D1 but enhanced expression of p21. Most importantly, upon CQ and NQ treatment

  20. Divorcing the Late Upper Palaeolithic demographic histories of mtDNA haplogroups M1 and U6 in Africa

    Directory of Open Access Journals (Sweden)

    Pennarun Erwan

    2012-12-01

    Full Text Available Abstract Background A Southwest Asian origin and dispersal to North Africa in the Early Upper Palaeolithic era has been inferred in previous studies for mtDNA haplogroups M1 and U6. Both haplogroups have been proposed to show similar geographic patterns and shared demographic histories. Results We report here 24 M1 and 33 U6 new complete mtDNA sequences that allow us to refine the existing phylogeny of these haplogroups. The resulting phylogenetic information was used to genotype a further 131 M1 and 91 U6 samples to determine the geographic spread of their sub-clades. No southwest Asian specific clades for M1 or U6 were discovered. U6 and M1 frequencies in North Africa, the Middle East and Europe do not follow similar patterns, and their sub-clade divisions do not appear to be compatible with their shared history reaching back to the Early Upper Palaeolithic. The Bayesian Skyline Plots testify to non-overlapping phases of expansion, and the haplogroups’ phylogenies suggest that there are U6 sub-clades that expanded earlier than those in M1. Some M1 and U6 sub-clades could be linked with certain events. For example, U6a1 and M1b, with their coalescent ages of ~20,000–22,000 years ago and earliest inferred expansion in northwest Africa, could coincide with the flourishing of the Iberomaurusian industry, whilst U6b and M1b1 appeared at the time of the Capsian culture. Conclusions Our high-resolution phylogenetic dissection of both haplogroups and coalescent time assessments suggest that the extant main branching pattern of both haplogroups arose and diversified in the mid-later Upper Palaeolithic, with some sub-clades concomitantly with the expansion of the Iberomaurusian industry. Carriers of these maternal lineages have been later absorbed into and diversified further during the spread of Afro-Asiatic languages in North and East Africa.

  1. Enhanced M1 macrophage polarization in human helicobacter pylori-associated atrophic gastritis and in vaccinated mice.

    Directory of Open Access Journals (Sweden)

    Marianne Quiding-Järbrink

    Full Text Available BACKGROUND: Infection with Helicobacter pylori triggers a chronic gastric inflammation that can progress to atrophy and gastric adenocarcinoma. Polarization of macrophages is a characteristic of both cancer and infection, and may promote progression or resolution of disease. However, the role of macrophages and their polarization during H. pylori infection has not been well defined. METHODOLOGY/PRINCIPAL FINDINGS: By using a mouse model of infection and gastric biopsies from 29 individuals, we have analyzed macrophage recruitment and polarization during H. pylori infection by flow cytometry and real-time PCR. We found a sequential recruitment of neutrophils, eosinophils and macrophages to the gastric mucosa of infected mice. Gene expression analysis of stomach tissue and sorted macrophages revealed that gastric macrophages were polarized to M1 after H. pylori infection, and this process was substantially accelerated by prior vaccination. Human H. pylori infection was characterized by a mixed M1/M2 polarization of macrophages. However, in H. pylori-associated atrophic gastritis, the expression of inducible nitric oxide synthase was markedly increased compared to uncomplicated gastritis, indicative of an enhanced M1 macrophage polarization in this pre-malignant lesion. CONCLUSIONS/SIGNIFICANCE: These results show that vaccination of mice against H. pylori amplifies M1 polarization of gastric macrophages, and that a similar enhanced M1 polarization is present in human H. pylori-induced atrophic gastritis.

  2. Effect of Cocoa Polyphenolic Extract on Macrophage Polarization from Proinflammatory M1 to Anti-Inflammatory M2 State

    Directory of Open Access Journals (Sweden)

    Laura Dugo

    2017-01-01

    Full Text Available Polyphenols-rich cocoa has many beneficial effects on human health, such as anti-inflammatory effects. Macrophages function as control switches of the immune system, maintaining the balance between pro- and anti-inflammatory activities. We investigated the hypothesis that cocoa polyphenol extract may affect macrophage proinflammatory phenotype M1 by favoring an alternative M2 anti-inflammatory state on macrophages deriving from THP-1 cells. Chemical composition, total phenolic content, and antioxidant capacity of cocoa polyphenols extracted from roasted cocoa beans were determined. THP-1 cells were activated with both lipopolysaccharides and interferon-γ for M1 or with IL-4 for M2 switch, and specific cytokines were quantified. Cellular metabolism, through mitochondrial oxygen consumption, and ATP levels were evaluated. Here, we will show that cocoa polyphenolic extract attenuated in vitro inflammation decreasing M1 macrophage response as demonstrated by a significantly lowered secretion of proinflammatory cytokines. Moreover, treatment of M1 macrophages with cocoa polyphenols influences macrophage metabolism by promoting oxidative pathways, thus leading to a significant increase in O2 consumption by mitochondrial complexes as well as a higher production of ATP through oxidative phosphorylation. In conclusion, cocoa polyphenolic extract suppresses inflammation mediated by M1 phenotype and influences macrophage metabolism by promoting oxidative pathways and M2 polarization of active macrophages.

  3. The M1 muscarinic receptor and its second messenger coupling in human neuroblastoma cells and transfected murine fibroblast cells

    International Nuclear Information System (INIS)

    Mei, Lin.

    1989-01-01

    The data of this study indicate that pirenzepine (PZ)-high affinity muscarinic receptors (mAChRs) are coupled to the hydrolysis of inositol lipids and not to the adenylate cyclase system in human neuroblastoma SH-SY5Y cells. The maximal carbachol(CCh)-stimulated [ 3 H]IP 1 accumulation in the SH-SY5Y cells was decreased in the presence of 1μg/ml pertussis toxin, suggesting that a pertussis toxin sensitive G-protein may be involved in the coupling. Several cell clones which express only M 1 mAChR were generated by transfecting the murine fibroblast B82 cells with the cloned rat genomic m 1 gene. The transfected B82 cells (cTB10) showed specific [ 3 H](-)QNB binding activity. The mAChRs in these cells are of the M 1 type defined by their high affinity for PZ and low affinity for AF-DX 116 and coupled to hydrolysis of inositol lipids, possibly via a pertussis toxin sensitive G protein. The relationship between the M 1 mAChR density and the receptor-mediated hydrolysis of inositol lipids was studied in 7 clones. The M 1 mAChR densities in these cells characterized by [ 3 H](-)MQNB binding ranged from 12 fmol/10 6 cells in LK3-1 cells to 260 fmol/10 6 cells in the LK3-8 cells

  4. Systematics of the excitation of M1 resonances in medium heavy nuclei by 200 MeV proton inelastic scattering

    International Nuclear Information System (INIS)

    Djalali, C.; Marty, N.; Morlet, M.

    1982-01-01

    In a series of seventeen nuclei ranging from 51 V to 140 Ca, broad resonance structures are observed at energies between 8 and 10 MeV, nearly mass independent. These resonances have very forward peaked angular distributions which imply that they are populated by an angular momentum transfer of zero. This together with the observed excitation energies suggests an M1 character for these resonances. In 51 V, 58 Ni, 60 Ni, 62 Ni, a sharp peak located at an excitation energy above the threshold for neutron emission is interpreted as a part of the T 0+1 component of the M1 resonances. Cross-sections are given for all the M1 resonances. For 58 Ni, 90 Zr, 92 Mo, 120 Sn and 140 Ca, an ''attenuation'' factor for the cross-sections is extracted in a OWIA calculation assuming simple shell model structures for these resonances

  5. Roles of transmembrane segment M1 of Na(+),K (+)-ATPase and Ca (2+)-ATPase, the gatekeeper and the pivot

    DEFF Research Database (Denmark)

    Einholm, Anja P.; Andersen, Jens Peter; Vilsen, Bente

    2007-01-01

    In this review we summarize mutagenesis work on the structure-function relationship of transmembrane segment M1 in the Na(+),K(+)-ATPase and the sarco(endo)plasmic reticulum Ca(2+)-ATPase. The original hypothesis that charged residues in the N-terminal part of M1 interact with the transported...... cations can be rejected. On the other hand hydrophobic residues in the middle part of M1 turned out to play crucial roles in Ca(2+) interaction/occlusion in Ca(2+)-ATPase and K(+) interaction/occlusion in Na(+),K(+)-ATPase. Leu(65) of the Ca(2+)-ATPase and Leu(99) of the Na(+),K(+)-ATPase, located...... of the extracytoplasmic gate in both the Ca(2+)-ATPase and the Na(+),K(+)-ATPase. Udgivelsesdato: 2007-Dec...

  6. Internal (m=1, n=1) and (m=2, n=1) resistive modes in the toroidal Tokomak with circular cross sections

    International Nuclear Information System (INIS)

    Bussac, M.N.; Pellat, R.; Edery, D.; Soule, J.L.

    1976-01-01

    A linear analysis is presented of the toroidal coupling between the internal resistive modes (m=1, n=1) and (m=2, n=1) in the Tokomak with circular cross sections. One includes the resistive and diamagnetic effects in the singular layers where the safety factor q takes respectively the values one and two. By expanding the MHD equations in powers of epsilon, the local inverse of the aspect ratio, one obtains a system of two coupled equations for the harmonic amplitudes. When the shear is finite on q=1, the toroidal coupling is negligible. In the opposite limit, one can explain: the experimental behaviour of the (m=1, n=1) mode before the internal disruption; the simultaneous observation of the modes (m=1, n=1) and [de

  7. Effective Lagrangians, Watson's theorem and the E2/M1 mixing ratio in the excitation of the Delta resonance

    International Nuclear Information System (INIS)

    Davidson, R.M.

    1992-01-01

    The author investigates theoretical uncertainties and model dependence in the extraction of the nucleon-delta(1232) electromagnetic transition amplitudes from the multipole data base. The starting point is an effective Lagrangian incorporating chiral symmetry, which includes at the tree level the pseudovector Born terms, leading t-channel vector meson exchanges, and s and u channel delta exchanges. The nucleon-delta magnetic dipole (M1) and electric quadrupole (E2) transition amplitudes are expressed in terms of two independent gauge couplings at the γNΔ vertex. After unitarizing the tree level amplitude, the gauge couplings are fitted to various multipole data sets, thus determining E2 and M1. Although there is much sensitivity to the method used to unitarize the amplitude, the author extracts the E2/M1 ratio to be negative, with a magnitude around 1.5%. 11 refs., 3 figs

  8. Disturbed mitochondrial function restricts glutamate uptake in the human Müller glia cell line, MIO-M1

    DEFF Research Database (Denmark)

    Vohra, Rupali; Gurubaran, Iswariyaraja Sridevi; Henriksen, Ulrik

    2017-01-01

    Using the human Müller cell line, MIO-M1, the aim was to study the impact of mitochondrial inhibition in Müller glia through antimycin A treatment. MIO-M1 cell survival, levels of released lactate, mitochondrial function, and glutamate uptake were studied in response to mitochondrial inhibition...... and glucose restriction. Lactate release decreased in response to glucose restriction. Combined glucose restriction and blocked mitochondrial activity decreased survival and caused collapse of the respiratory chain measured by oxygen consumption rate and extracellular acidification rate. Mitochondrial...... inhibition caused impaired glutamate uptake and decreased mRNA expression of the glutamate transporter, EAAT1. Over all, we show important roles of mitochondrial activity in MIO-M1 cell function and survival....

  9. Further optimization of the M1 PAM VU0453595: Discovery of novel heterobicyclic core motifs with improved CNS penetration.

    Science.gov (United States)

    Panarese, Joseph D; Cho, Hykeyung P; Adams, Jeffrey J; Nance, Kellie D; Garcia-Barrantes, Pedro M; Chang, Sichen; Morrison, Ryan D; Blobaum, Anna L; Niswender, Colleen M; Stauffer, Shaun R; Conn, P Jeffrey; Lindsley, Craig W

    2016-08-01

    This Letter describes the continued chemical optimization of the VU0453595 series of M1 positive allosteric modulators (PAMs). By surveying alternative 5,6- and 6,6-heterobicylic cores for the 6,7-dihydro-5H-pyrrolo[3,4-b]pyridine-5-one core of VU453595, we found new cores that engendered not only comparable or improved M1 PAM potency, but significantly improved CNS distribution (Kps 0.3-3.1). Moreover, this campaign provided fundamentally distinct M1 PAM chemotypes, greatly expanding the available structural diversity for this valuable CNS target, devoid of hydrogen-bond donors. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Task-specificity of unilateral anodal and dual-M1 tDCS effects on motor learning.

    Science.gov (United States)

    Karok, Sophia; Fletcher, David; Witney, Alice G

    2017-01-08

    Task-specific effects of transcranial direct current stimulation (tDCS) on motor learning were investigated in 30 healthy participants. In a sham-controlled, mixed design, participants trained on 3 different motor tasks (Purdue Pegboard Test, Visuomotor Grip Force Tracking Task and Visuomotor Wrist Rotation Speed Control Task) over 3 consecutive days while receiving either unilateral anodal over the right primary motor cortex (M1), dual-M1 or sham stimulation. Retention sessions were administered 7 and 28 days after the end of training. In the Purdue Pegboard Test, both anodal and dual-M1 stimulation reduced average completion time approximately equally, an improvement driven by online learning effects and maintained for about 1 week. The Visuomotor Grip Force Tracking Task and the Visuomotor Wrist Rotation Speed Control Task were associated with an advantage of dual-M1 tDCS in consolidation processes both between training sessions and when testing at long-term retention; both were maintained for at least 1 month. This study demonstrates that M1-tDCS enhances and sustains motor learning with different electrode montages. Stimulation-induced effects emerged at different learning phases across the tasks, which strongly suggests that the influence of tDCS on motor learning is dynamic with respect to the functional recruitment of the distributed motor system at the time of stimulation. Divergent findings regarding M1-tDCS effects on motor learning may partially be ascribed to task-specific consequences and the effects of offline consolidation. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. ADAM-17 is a poor prognostic indicator for patients with hilar cholangiocarcinoma and is regulated by FoxM1.

    Science.gov (United States)

    Jiao, Xiaodong; Yu, Wenlong; Qian, Jianxin; Chen, Ying; Wei, Peilian; Fang, Wenzheng; Yu, Guanzhen

    2018-05-18

    A-disintegrin and metalloproteinases (ADAMs) are members of a family of multidomain transmembrane and secreted proteins. Specific ADAMs are upregulated in human cancers and correlated with tumor progression and poor outcome, but rarely studied in human hilar cholangiocarcinoma (HC). This study aimed to explore the expression profiles of ADAMs and their potential underlying mechanisms promoting cancer progression. mRNA expression of ADAM-9, - 10, - 11, - 12, - 15, - 17, - 28, and - 33 was analyzed in human hilar cholangiocarcinoma (HC) samples. Immunohistochemical (IHC) analysis was used to detect the expression of ADAM-10, - 17, - 28, and FoxM1 in HC. The regulation of ADAM-17 by FoxM1 and their functional study was investigated in vivo and in vitro. ADAM-10, - 17, and - 28 were upregulated in tumors compared with matched non-cancerous tissues. IHC analysis revealed increased expression of ADAM-10, - 17, and - 28 in HC cells, and ADAM17 seems to be an independent prognostic factor. ADAM-17 is regulated by FoxM1. A decrease in the expression of ADAM-17 by silencing FoxM1 led to an inhibition of cell proliferation, tumor growth, and the production of tumor necrosis factor α. IHC analysis showed co-expression of FoxM1 and ADAM-17 in HC specimens. The findings of the present study show an important role of the cross-talk among FoxM1, ADAM-17, and TNFa in HC development and progression.

  12. GST M1-T1 null allele frequency patterns in geographically assorted human populations: a phylogenetic approach.

    Directory of Open Access Journals (Sweden)

    Senthilkumar Pitchalu Kasthurinaidu

    Full Text Available Genetic diversity in drug metabolism and disposition is mainly considered as the outcome of the inter-individual genetic variation in polymorphism of drug-xenobiotic metabolizing enzyme (XME. Among the XMEs, glutathione-S-transferases (GST gene loci are an important candidate for the investigation of diversity in allele frequency, as the deletion mutations in GST M1 and T1 genotypes are associated with various cancers and genetic disorders of all major Population Affiliations (PAs. Therefore, the present population based phylogenetic study was focused to uncover the frequency distribution pattern in GST M1 and T1 null genotypes among 45 Geographically Assorted Human Populations (GAHPs. The frequency distribution pattern for GST M1 and T1 null alleles have been detected in this study using the data derived from literatures representing 44 populations affiliated to Africa, Asia, Europe, South America and the genome of PA from Gujarat, a region in western India. Allele frequency counting for Gujarat PA and scattered plot analysis for geographical distribution among the PAs were performed in SPSS-21. The GST M1 and GST T1 null allele frequencies patterns of the PAs were computed in Seqboot, Gendist program of Phylip software package (3.69 versions and Unweighted Pair Group method with Arithmetic Mean in Mega-6 software. Allele frequencies from South African Xhosa tribe, East African Zimbabwe, East African Ethiopia, North African Egypt, Caucasian, South Asian Afghanistan and South Indian Andhra Pradesh have been identified as the probable seven patterns among the 45 GAHPs investigated in this study for GST M1-T1 null genotypes. The patternized null allele frequencies demonstrated in this study for the first time addresses the missing link in GST M1-T1 null allele frequencies among GAHPs.

  13. The Armys M-1 Abrams, M-2/M-3 Bradley, and M-1126 Stryker: Background and Issues for Congress

    Science.gov (United States)

    2016-04-05

    the Army John McHugh , urging instead the limited production of 70 M-1A2SEPv2 tanks per year from FY2013 to FY2017. 32 Congress subsequently decided...House Members sent a letter to Secretary of the Army McHugh expressing concern over the Army’s failure to fund production of the M-1A2. Congress...John McHugh by Rep. Sander Levin and Rep. Mike Rogers, May 6, 2011. 33 See CRS Reports: CRS Report R43323, Defense: FY2014 Authorization and

  14. E2,M1 multipole mixing ratios in even-even nuclei, 58< or =A< or =150

    International Nuclear Information System (INIS)

    Krane, K.S.

    1977-01-01

    A survey is presented of E2,M1 multipole mixing ratios of gamma-ray transitions in even-even nuclei in the mass range 58< or =A< or =150. Angular distribution and correlation data from the literature are analyzed in terms of a consistent choice of the phase relationship between the E2 and M1 matrix elements. A set of recommended values of the mixing ratios is included based on averages of results from various studies. The survey includes data available in the literature up to December 1976

  15. E2,M1 Multipole mixing ratios in odd-mass nuclei, 59< or =A< or =149

    International Nuclear Information System (INIS)

    Krane, K.S.

    1977-01-01

    A survey is presented of the E2,M1 mxing ratios of gamma-ray transitions in odd-mass nuclei with 59< or =A< or =149. Angular distribution and correlation data from the literature are analyzed in terms of a consistent choice of the phase relationship between the E2 and M1 matrix elements. A set of recommended values of the mixing ratios is included, based on averages of results from various studies. The survey includes data available in the literature up to September 1976

  16. Achievements and Prospects in Electrochemical-Based Biosensing Platforms for Aflatoxin M1 Detection in Milk and Dairy Products

    Directory of Open Access Journals (Sweden)

    Ana-Maria Gurban

    2017-12-01

    Full Text Available Aflatoxins, which are mainly produced by Aspergillus flavus and parasiticus growing on plants and products stored under inappropriate conditions, represent the most studied group of mycotoxins. Contamination of human and animal milk with aflatoxin M1, the hydroxylated metabolite of aflatoxin B1, is an important health risk factor due to its carcinogenicity and mutagenicity. Due to the low concentration of this aflatoxin in milk and milk products, the analytical methods used for its quantification have to be highly sensitive, specific and simple. This paper presents an overview of the analytical methods, especially of the electrochemical immunosensors and aptasensors, used for determination of aflatoxin M1.

  17. Cardiosphere-Derived Cells Facilitate Heart Repair by Modulating M1/M2 Macrophage Polarization and Neutrophil Recruitment.

    Directory of Open Access Journals (Sweden)

    Al Shaimaa Hasan

    Full Text Available Cardiosphere-derived cells (CDCs, one of the promising stem cell sources for myocardial repair, have been tested in clinical trials and resulted in beneficial effects; however, the relevant mechanisms are not fully understood. In this study, we examined the hypothesis that CDCs favor heart repair by switching the macrophages from a pro-inflammatory phenotype (M1 into a regulatory anti-inflammatory phenotype (M2. Macrophages from mice were cultured with CDCs-conditioned medium or with fibroblasts-conditioned medium as a control. Immunostaining showed that CDCs-conditioned medium significantly enhanced the expression of CD206 (a marker for M2 macrophages, but decreased the expression of CD86 (a marker for M1 macrophages 3 days after culture. For animal studies, we used an acute myocardial infarction model of mice. We injected CDCs, fibroblasts, or saline only into the border zone of infarction. Then we collected the heart tissues for histological analysis 5 and 14 days after treatment. Compared with control animals, CDCs treatment significantly decreased M1 macrophages and neutrophils but increased M2 macrophages in the infarcted heart. Furthermore, CDCs-treated mice had reduced infarct size and fewer apoptotic cells compared to the controls. Our data suggest that CDCs facilitate heart repair by modulating M1/M2 macrophage polarization and neutrophil recruitment, which may provide a new insight into the mechanisms of stem cell-based myocardial repair.

  18. Cardiosphere-Derived Cells Facilitate Heart Repair by Modulating M1/M2 Macrophage Polarization and Neutrophil Recruitment

    Science.gov (United States)

    Hasan, Al Shaimaa; Luo, Lan; Yan, Chen; Zhang, Tian-Xia; Urata, Yoshishige; Goto, Shinji; Mangoura, Safwat A.; Abdel-Raheem, Mahmoud H.; Zhang, Shouhua; Li, Tao-Sheng

    2016-01-01

    Cardiosphere-derived cells (CDCs), one of the promising stem cell sources for myocardial repair, have been tested in clinical trials and resulted in beneficial effects; however, the relevant mechanisms are not fully understood. In this study, we examined the hypothesis that CDCs favor heart repair by switching the macrophages from a pro-inflammatory phenotype (M1) into a regulatory anti-inflammatory phenotype (M2). Macrophages from mice were cultured with CDCs-conditioned medium or with fibroblasts-conditioned medium as a control. Immunostaining showed that CDCs-conditioned medium significantly enhanced the expression of CD206 (a marker for M2 macrophages), but decreased the expression of CD86 (a marker for M1 macrophages) 3 days after culture. For animal studies, we used an acute myocardial infarction model of mice. We injected CDCs, fibroblasts, or saline only into the border zone of infarction. Then we collected the heart tissues for histological analysis 5 and 14 days after treatment. Compared with control animals, CDCs treatment significantly decreased M1 macrophages and neutrophils but increased M2 macrophages in the infarcted heart. Furthermore, CDCs-treated mice had reduced infarct size and fewer apoptotic cells compared to the controls. Our data suggest that CDCs facilitate heart repair by modulating M1/M2 macrophage polarization and neutrophil recruitment, which may provide a new insight into the mechanisms of stem cell-based myocardial repair. PMID:27764217

  19. Large low-energy M1 strength for ^{56,57}Fe within the nuclear shell model.

    Science.gov (United States)

    Brown, B Alex; Larsen, A C

    2014-12-19

    A strong enhancement at low γ-ray energies has recently been discovered in the γ-ray strength function of ^{56,57}Fe. In this work, we have for the first time obtained theoretical γ decay spectra for states up to ≈8  MeV in excitation for ^{56,57}Fe. We find large B(M1) values for low γ-ray energies that provide an explanation for the experimental observations. The role of mixed E2 transitions for the low-energy enhancement is addressed theoretically for the first time, and it is found that they contribute a rather small fraction. Our calculations clearly show that the high-ℓ(=f) diagonal terms are most important for the strong low-energy M1 transitions. As such types of 0ℏω transitions are expected for all nuclei, our results indicate that a low-energy M1 enhancement should be present throughout the nuclear chart. This could have far-reaching consequences for our understanding of the M1 strength function at high excitation energies, with profound implications for astrophysical reaction rates.

  20. HIV Nef-M1 Effects on Colorectal Cancer Growth in Tumor-induced Spleens and Hepatic Metastasis

    Science.gov (United States)

    Harrington, Willie; Bond, Vincent; Huang, Ming Bo; Powell, Michael; Lillard, James; Manne, Upender; Bumpers, Harvey

    2010-01-01

    CXCR4 receptors have been implicated in tumorigenesis and proliferation, making it a potential target for colorectal cancer therapy. Expression of this chemokine receptor on cellular surfaces appears to promote metastasis by directly stimulating tumor cell migration and invasion. The receptor/ligand, CXCR4/SDF-1α, pair are critically important to angiogenesis and vascular remodeling which supports cancer proliferation. Our work has shown that a novel apoptotic peptide of HIV-1, Nef-M1, can act as a CXCR4 antagonist, inducing apoptosis in CXCR4 containing cells. Four colorectal tumor cell lines (HT-29, LS174t, SW480, WiDr), were evaluated for their response to Nef-M1 peptide via in vivo and in vitro. The presence of CXCR4 receptors on tumor cells was determined using immunohistochemical and RT-PCR analyses. Solid xenografts derived from tumor cell lines grown in SCID mice, were evaluated for the persistence of the receptor. Xenografts propagated in SCID mice from each of the four cell lines demonstrated high levels of receptor expression as well. The effects of Nef-M1 in vivo via splenic injected mice and subsequent hepatic metastasis also demonstrated dramatic reduction of primary tumor growth in the spleen and secondary invasion of the liver. We concluded that Nef-M1 peptide, through physical interaction(s) with CXCR4, drives apoptotic reduction in in vivo primary tumor growth and metastasis. PMID:20383296

  1. Selective incorporation of vRNP into influenza A virions determined by its specific interaction with M1 protein

    Energy Technology Data Exchange (ETDEWEB)

    Chaimayo, Chutikarn [Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642 (United States); Department of Microbiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700 (Thailand); Hayashi, Tsuyoshi; Underwood, Andrew; Hodges, Erin [Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642 (United States); Takimoto, Toru, E-mail: toru_takimoto@urmc.rochester.edu [Department of Microbiology and Immunology, University of Rochester Medical Center, Rochester, NY 14642 (United States)

    2017-05-15

    Influenza A viruses contain eight single-stranded, negative-sense RNA segments as viral genomes in the form of viral ribonucleoproteins (vRNPs). During genome replication in the nucleus, positive-sense complementary RNPs (cRNPs) are produced as replicative intermediates, which are not incorporated into progeny virions. To analyze the mechanism of selective vRNP incorporation into progeny virions, we quantified vRNPs and cRNPs in the nuclear and cytosolic fractions of infected cells, using a strand-specific qRT-PCR. Unexpectedly, we found that cRNPs were also exported to the cytoplasm. This export was chromosome region maintenance 1 (CRM1)-independent unlike that of vRNPs. Although both vRNPs and cRNPs were present in the cytosol, viral matrix (M1) protein, a key regulator for viral assembly, preferentially bound vRNPs over cRNPs. These results indicate that influenza A viruses selectively uptake cytosolic vRNPs through a specific interaction with M1 during viral assembly. - Highlights: •Influenza cRNPs are exported from the nucleus of an infected cell via a CRM1-independent pathway. •Influenza A viruses selectively incorporate cytosolic vRNPs through a specific interaction with M1 during viral assembly. •M1 dissociates from vRNP export complex after nuclear export, and is re-associated with vRNPs at the plasma membrane.

  2. Differential effects of m1 and m2 receptor antagonists in perirhinal cortex on visual recognition memory in monkeys.

    Science.gov (United States)

    Wu, Wei; Saunders, Richard C; Mishkin, Mortimer; Turchi, Janita

    2012-07-01

    Microinfusions of the nonselective muscarinic antagonist scopolamine into perirhinal cortex impairs performance on visual recognition tasks, indicating that muscarinic receptors in this region play a pivotal role in recognition memory. To assess the mnemonic effects of selective blockade in perirhinal cortex of muscarinic receptor subtypes, we locally infused either the m1-selective antagonist pirenzepine or the m2-selective antagonist methoctramine in animals performing one-trial visual recognition, and compared these scores with those following infusions of equivalent volumes of saline. Compared to these control infusions, injections of pirenzepine, but not of methoctramine, significantly impaired recognition accuracy. Further, similar doses of scopolamine and pirenzepine yielded similar deficits, suggesting that the deficits obtained earlier with scopolamine were due mainly, if not exclusively, to blockade of m1 receptors. The present findings indicate that m1 and m2 receptors have functionally dissociable roles, and that the formation of new visual memories is critically dependent on the cholinergic activation of m1 receptors located on perirhinal cells. Published by Elsevier Inc.

  3. Immunocytochemical demonstration of M1 muscarinic acetylcholine receptors at the presynaptic and postsynaptic membranes of rat diaphragm endplates

    Czech Academy of Sciences Publication Activity Database

    Malomouzh, A. I.; Arkhipova, S. S.; Nikolsky, E. E.; Vyskočil, František

    2011-01-01

    Roč. 60, č. 1 (2011), s. 185-188 ISSN 0862-8408 R&D Projects: GA AV ČR(CZ) IAA500110905; GA ČR GA202/09/0806 Institutional research plan: CEZ:AV0Z50110509 Keywords : skeletal muscle * M1 muscarinic receptor Subject RIV: ED - Physiology Impact factor: 1.555, year: 2011

  4. Calculation of the single lepton SUSY analysis limits in the cMSSM m0-m1/2 plane

    CERN Document Server

    Megas, Efstathios

    2014-01-01

    The goal of the summer student project was the calculation of the single lepton SUSY analysis limits in the cMSSM $m_0$-$m_{1/2}$ plane. To this end, the analysis code, the production of the ntuples and a familarization with the higgs combination tool was needed.

  5. The muscarinic M1/M4 receptor agonist xanomeline exhibits antipsychotic-like activity in Cebus apella monkeys

    DEFF Research Database (Denmark)

    Andersen, Maibritt B; Fink-Jensen, Anders; Peacock, Linda

    2003-01-01

    Xanomeline is a muscarinic M(1)/M(4) preferring receptor agonist with little or no affinity for dopamine receptors. The compound reduces psychotic-like symptoms in patients with Alzheimer's disease and exhibits an antipsychotic-like profile in rodents without inducing extrapyramidal side effects ...

  6. Activation of muscarinic M-1 cholinoceptors by curcumin to increase glucose uptake into skeletal muscle isolated from Wistar rats.

    Science.gov (United States)

    Cheng, Tse-Chou; Lin, Chian-Shiung; Hsu, Chih-Chieh; Chen, Li-Jen; Cheng, Kai-Chun; Cheng, Juei-Tang

    2009-11-20

    Curcumin, an active principle contained in rhizome of Curcuma longa, has been mentioned to show merit for diabetes through its anti-oxidative and anti-inflammatory properties. In the present study, we found that curcumin caused a concentration-dependent increase of glucose uptake into skeletal muscle isolated from Wistar rats. This action was inhibited by pirenzepine at concentration enough to block muscarinic M-1 cholinoceptor (M(1)-mAChR). In radioligand binding assay, the binding of [(3)H]-pirenzepine was also displaced by curcumin in a concentration-dependent manner. In the presence of inhibitors for PLC-PI3K pathway, either U73122 (phospholipase C inhibitor) or LY294002 (phosphoinositide 3-kinase inhibitor), curcumin-stimulated glucose uptake into skeletal muscle was markedly reduced. In Western blotting analysis, the membrane protein level of glucose transporter 4 (GLUT4) increased by curcumin was also reversed by blockade of M(1)-mAChR or PLC-PI3K pathway in a same manner. In conclusion, the obtained results suggest that curcumin can activate M(1)-mAChR at concentrations lower than to scavenge free radicals for increase of glucose uptake into skeletal muscle through PLC-PI3-kinase pathway.

  7. Activation of muscarinic M-1 cholinoceptors by curcumin to increase contractility in urinary bladder isolated from Wistar rats.

    Science.gov (United States)

    Cheng, Tse-Chou; Lu, Chih-Cheng; Chung, Hsien-Hui; Hsu, Chih-Chieh; Kakizawa, Nozomi; Yamada, Shizuo; Cheng, Juei-Tang

    2010-04-05

    Curcumin is an active principle contained in rhizome of Curcuma longa, and it has been recently mentioned to show affinity to muscarinic M-1 cholinoceptors (M(1)-mAChR). In the present study, we found that curcumin caused a concentration-dependent increase of muscle tone in urinary bladder isolated from Wistar rats. This action was inhibited by pirenzepine at concentration enough to block M(1)-mAChR. In radioligand-binding assay, specific binding of [(3)H]-oxotremorine (OXO-M) in the rat bladder homogenates was also displaced by curcumin in a concentration-dependent manner. In the presence of inhibitors for PLC-PKC pathway, either U73122 (phospholipase C inhibitor) or chelerythrine (protein kinase C inhibitor), curcumin-stimulated contraction in urinary bladder was markedly reduced. In conclusion, the obtained results suggest that curcumin can activate M(1)-mAChR at concentrations lower than to scavenge free radicals to increase of muscle tone in urinary bladder through PLC-PKC pathway.

  8. Selective incorporation of vRNP into influenza A virions determined by its specific interaction with M1 protein

    International Nuclear Information System (INIS)

    Chaimayo, Chutikarn; Hayashi, Tsuyoshi; Underwood, Andrew; Hodges, Erin; Takimoto, Toru

    2017-01-01

    Influenza A viruses contain eight single-stranded, negative-sense RNA segments as viral genomes in the form of viral ribonucleoproteins (vRNPs). During genome replication in the nucleus, positive-sense complementary RNPs (cRNPs) are produced as replicative intermediates, which are not incorporated into progeny virions. To analyze the mechanism of selective vRNP incorporation into progeny virions, we quantified vRNPs and cRNPs in the nuclear and cytosolic fractions of infected cells, using a strand-specific qRT-PCR. Unexpectedly, we found that cRNPs were also exported to the cytoplasm. This export was chromosome region maintenance 1 (CRM1)-independent unlike that of vRNPs. Although both vRNPs and cRNPs were present in the cytosol, viral matrix (M1) protein, a key regulator for viral assembly, preferentially bound vRNPs over cRNPs. These results indicate that influenza A viruses selectively uptake cytosolic vRNPs through a specific interaction with M1 during viral assembly. - Highlights: •Influenza cRNPs are exported from the nucleus of an infected cell via a CRM1-independent pathway. •Influenza A viruses selectively incorporate cytosolic vRNPs through a specific interaction with M1 during viral assembly. •M1 dissociates from vRNP export complex after nuclear export, and is re-associated with vRNPs at the plasma membrane.

  9. Activation of M1 macrophages in sepsis-induced acute kidney injury in response to heparin-binding protein.

    Directory of Open Access Journals (Sweden)

    Li Xing

    Full Text Available In the early stage of sepsis, M1 macrophages result in the production of inflammatory mediators and AKI. Heparin-binding protein (HBP have been shown to play important roles in sepsis-induced AKI. In this study, we investigate the association of HBP with M1 macrophages in sepsis-induced AKI.Male C57BL6 mice were subjected to cecal ligation and puncture (CLP or sham surgery. Biochemical and histological renal damage was assessed. Macrophage infiltration was assessed by immunohistochemistry. RT-PCR was used to investigate the expression of heparin-binding protein (HBP, the inducible nitric oxide synthase (iNOS and arginase 1 (Arg-1 mRNAs. Western blots were performed to assay the tissue levels of HBP, tumor necrosis factor alpha (TNF-α and interleukin-6 (IL-6.High levels of HBP were obviously detected 24 h after sepsis-induced AKI. Heparin inhibited HBP expression during sepsis-induced AKI. The suppression of HBP expression by heparin injection after the establishment of sepsis-induced AKI resulted in a reduction in renal injury severity accompanied with a significant repression of M1 macrophage activation and expression of TNF-α and IL-6.HBP plays an important role in the initial inflammatory reaction associated with sepsis-induced AKI, presumably by activating M1 macrophages and suppressing TNF-α and IL-6 secretion.

  10. Allosteric modulation by persistent binding of xanomeline of the interaction of competitive ligands with the M1 muscarinic acetylcholine receptor

    Czech Academy of Sciences Publication Activity Database

    Jakubík, Jan; Tuček, Stanislav; El-Fakahany, E. E.

    2002-01-01

    Roč. 301, č. 3 (2002), s. 1033-1041 ISSN 0022-3565 R&D Projects: GA ČR GP305/01/D119 Grant - others:NIH(US) NS25743 Institutional research plan: CEZ:AV0Z5011922 Keywords : xanomeline * M(1) muscarinic acetylcholine receptor Subject RIV: FH - Neurology Impact factor: 3.991, year: 2002

  11. Design, Engineering and Application of an Amyloidogenic Protein, SBAFP-m1, for use in Nanotechnological Applications

    Science.gov (United States)

    Peralta, Maria del Refugio

    Nanotechnology relies on collaborations across scientific disciplines such as physics, engineering, chemistry and biology. In nanotechnology, researchers manipulate molecules on the nanometer scale for various applications, ranging from tissue engineering, nanowire synthesis, and alternative energy devices. By utilizing various biological scaffolds, namely amyloid fibrils, the work of nanometer molecular control can be achieved through the use of self-assembly systems. Here, a systematic design scheme was developed to engineer protein based amyloid fibrils and was successfully applied to the design of two, unique self-assembled monomers, SBAFP-m1 and RGAFP-m1, from naturally occurring ice binding proteins found in insects and plants. A highly idealized, in-register dimer interface was designed and experimentally synthesized and demonstrated to form micron long amyloid fibrils (Chapter 2). The strength and resistance of the designer amyloid fibrils formed by SBAFP-m1 were probed in Chapter 3. Most notably, the ultimate tensile strength of SBAFP-m1 fibrils was experimentally determined to be 2.1 +/- 1.7 GPa, on par with that of naturally occurring amyloid fibrils in literature and steel. The fibrils were found to maintain their beta-sheet structure over a wide range of temperatures, from - 80 °C to 90 °C. Fibrils were resistant to common protein denaturants like 8M urea, 2.5 M guanidine hydrochloride, 2.5 M NaCl, organic solvents (methanol, ethanol, isopropanol and acetone), and across the pH range two to 11. SBAFP-m1 was mutated to add a 5x cysteine tag to the N-terminus, allowing for gold nanoparticle conjugation along the fibril axis (Chapter 4). The gold-conjugated fibrils were then enhanced with silver to produce nanowires. Various attempts to selectively synthesize heterogeneous fibrils from SBAFP-m1 mutants were attempted in Chapter 5. An attempt to de-stabilize the homogeneous fibril assembly through unfavorable homogeneous protein interactions was not

  12. Identification of the GST-T1 and GST-M1 null genotypes using high resolution melting analysis.

    Science.gov (United States)

    Drobná, Zuzana; Del Razo, Luz Maria; Garcia-Vargas, Gonzalo; Sánchez-Ramírez, Blanca; González-Horta, Carmen; Ballinas-Casarrubias, Lourdes; Loomis, Dana; Stýblo, Miroslav

    2012-01-13

    Glutathione S-transferases, including GST-T1 and GST-M1, are known to be involved in the phase II detoxification pathways for xenobiotics as well as in the metabolism of endogenous compounds. Polymorphisms in these genes have been linked to an increased susceptibility to carcinogenesis and associated with risk factors that predispose to certain inflammatory diseases. In addition, GST-T1 and GST-M1 null genotypes have been shown to be responsible for interindividual variations in the metabolism of arsenic, a known human carcinogen. To assess the specific GST genotypes in the Mexican population chronically exposed to arsenic, we have developed a multiplex High Resolution Melting PCR (HRM-PCR) analysis using a LightCycler480 instrument. This method is based on analysis of the PCR product melting curve that discriminates PCR products according to their lengths and base sequences. Three pairs of primers that specifically recognize GST-T1, GST-M1, and β-globin, an internal control, to produce amplicons of different length were designed and combined with LightCycler480 High Resolution Melting Master Mix containing ResoLight, a completely saturating DNA dye. Data collected from melting curve analysis were evaluated using LightCycler480 software to determine specific melting temperatures of individual melting curves representing target genes. Using this newly developed multiplex HRM-PCR analysis, we evaluated GST-T1 and GST-M1 genotypes in 504 DNA samples isolated from the blood of individuals residing in Zimapan, Lagunera, and Chihuahua regions in Mexico. We found that the Zimapan and Lagunera populations have similar GST-T1 and GST-M1 genotype frequencies which differ from those of the Chihuahua population. In addition, 14 individuals have been identified as carriers of the double null genotype, i.e., null genotypes in both GST-T1 and GST-M1 genes. Although this procedure does not distinguish between biallelic (+/+) and monoallelic (+/-) genotypes, it can be used in an

  13. Resveratrol regulates microglia M1/M2 polarization via PGC-1α in conditions of neuroinflammatory injury.

    Science.gov (United States)

    Yang, Xiaodong; Xu, Shaoqing; Qian, Yiwei; Xiao, Qin

    2017-08-01

    Microglia are the primary cells that exert immune function in the central nervous system (CNS), and accumulating evidence suggests that microglia act as key players in the initiation of neurodegenerative diseases. It is now well recognized that microglia have functional plasticity and dual phenotypes, proinflammatory M1 and anti-inflammatory M2 phenotypes. Inhibiting the M1 phenotype while stimulating the M2 phenotype has been suggested as a potential therapeutic approach for the treatment of neuroinflammation-related diseases. Resveratrol has been demonstrated to exert anti-inflammatory effects by suppressing M1 microglia activation. However, the role of resveratrol in regulating microglia polarization and the molecular mechanisms involved have not been fully clarified. In this study, we tested whether resveratrol could suppress microglia activation by promoting microglia polarization toward the M2 phenotype via PGC-1α by measuring M1 and M2 markers in vitro and in vivo. Our study demonstrated that resveratrol reduced inflammatory damage and promoted microglia polarization to the M2 phenotype in LPS-induced neuroinflammation. In addition, resveratrol ameliorated LPS-induced sickness behavior in mice. The promoting effects of resveratrol on M2 polarization were attenuated by knocking down PGC-1α. PGC-1α not only suppressed LPS-evoked M1 marker expression by inhibition of NF-κB activity but also increased M2 marker expression by coactivation of the STAT6 and STAT3 pathways. We propose that overexpression PGC-1α by resveratrol could be a potential therapeutic approach to suppress neuroinflammation by regulating microglia polarization. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Truncated thioredoxin (Trx-80) promotes pro-inflammatory macrophages of the M1 phenotype and enhances atherosclerosis.

    Science.gov (United States)

    Mahmood, Dler Faieeq Darweesh; Abderrazak, Amna; Couchie, Dominique; Lunov, Oleg; Diderot, Vimala; Syrovets, Tatiana; Slimane, Mohamed-Naceur; Gosselet, Fabien; Simmet, Thomas; Rouis, Mustapha; El Hadri, Khadija

    2013-07-01

    Vascular cells are particularly susceptible to oxidative stress that is believed to play a key role in the pathogenesis of cardiovascular disorders. Thioredoxin-1 (Trx-1) is an oxidative stress-limiting protein with anti-inflammatory and anti-apoptotic properties. In contrast, its truncated form (Trx-80) exerts pro-inflammatory effects. Here we analyzed whether Trx-80 might exert atherogenic effects by promoting macrophage differentiation into the M1 pro-inflammatory phenotype. Trx-80 at 1 µg/ml significantly attenuated the polarization of anti-inflammatory M2 macrophages induced by exposure to either IL-4 at 15 ng/ml or IL-4/IL-13 (10 ng/ml each) in vitro, as evidenced by the expression of the characteristic markers, CD206 and IL-10. By contrast, in LPS-challenged macrophages, Trx-80 significantly potentiated the differentiation into inflammatory M1 macrophages as indicated by the expression of the M1 cytokines, TNF-α and MCP-1. When Trx-80 was administered to hyperlipoproteinemic ApoE2.Ki mice at 30 µg/g body weight (b.w.) challenged either with LPS at 30 µg/30 g (b.w.) or IL-4 at 500 ng/30 g (b.w.), it significantly induced the M1 phenotype but inhibited differentiation of M2 macrophages in thymus and liver. When ApoE2.Ki mice were challenged once weekly with LPS for 5 weeks, they showed severe atherosclerotic lesions enriched with macrophages expressing predominantly M1 over M2 markers. Such effect was potentiated when mice received daily, in addition to LPS, the Trx-80. Moreover, the Trx-80 treatment led to a significantly increased aortic lesion area. The ability of Trx-80 to promote differentiation of macrophages into the classical proinflammatory phenotype may explain its atherogenic effects in cardiovascular diseases. Copyright © 2013 Wiley Periodicals, Inc.

  15. Enhanced muscarinic M1 receptor gene expression in the corpus striatum of streptozotocin-induced diabetic rats

    Directory of Open Access Journals (Sweden)

    Mathew Jobin

    2009-04-01

    Full Text Available Abstract Acetylcholine (ACh, the first neurotransmitter to be identified, regulate the activities of central and peripheral functions through interactions with muscarinic receptors. Changes in muscarinic acetylcholine receptor (mAChR have been implicated in the pathophysiology of many major diseases of the central nervous system (CNS. Previous reports from our laboratory on streptozotocin (STZ induced diabetic rats showed down regulation of muscarinic M1 receptors in the brainstem, hypothalamus, cerebral cortex and pancreatic islets. In this study, we have investigated the changes of acetylcholine esterase (AChE enzyme activity, total muscarinic and muscarinic M1 receptor binding and gene expression in the corpus striatum of STZ – diabetic rats and the insulin treated diabetic rats. The striatum, a neuronal nucleus intimately involved in motor behaviour, is one of the brain regions with the highest acetylcholine content. ACh has complex and clinically important actions in the striatum that are mediated predominantly by muscarinic receptors. We observed that insulin treatment brought back the decreased maximal velocity (Vmax of acetylcholine esterase in the corpus striatum during diabetes to near control state. In diabetic rats there was a decrease in maximal number (Bmax and affinity (Kd of total muscarinic receptors whereas muscarinic M1 receptors were increased with decrease in affinity in diabetic rats. We observed that, in all cases, the binding parameters were reversed to near control by the treatment of diabetic rats with insulin. Real-time PCR experiment confirmed the increase in muscarinic M1 receptor gene expression and a similar reversal with insulin treatment. These results suggest the diabetes-induced changes of the cholinergic activity in the corpus striatum and the regulatory role of insulin on binding parameters and gene expression of total and muscarinic M1 receptors.

  16. Electric conductivity of double fluorides in the systems M1F-Th(U)F4(M1=K, Tl) and M2F2-ThF4(M2=Ca, Sr, Ba)

    International Nuclear Information System (INIS)

    Murin, I.V.; Andreev, A.M.; Amelin, Yu.V.

    1982-01-01

    The temperature dependence of electric conductivity of some double fluorides formed in the systems M 1 F-Th(U)F 4 (M 1 =K, Tl) and M 2 F 2 -ThF 4 (M 2 =Ca, Sr, Ba) as well as UF 3 in a wide temperature range is studied. It is shown that the values of electric conductivity and activation energy of these fluorides depend on the compound structure and cation nature. The temperature electric conductivity dependence for double fluorides with the tysonite structure is close to the lanthanum fluoride dependence. Taking into account low electron electric conductivity component the conclusion is drawn that the investigated compounds can be used as solid electrolytes

  17. Proto-planetary nebulae. I. The extreme bipolar nebulae M2-9 and M1-91

    International Nuclear Information System (INIS)

    Goodrich, R.W.

    1991-01-01

    Results are presented on a long-slit optical spectroscopy measurements of the prototype bipolar planetary nebula M2-9 and the M1-91 bipolar nebula, performed in order to determine the nature of the morphology of the wings of these two nebulae. It is concluded that the overall bipolar morphologies of these nebulae might be due to the orbital motions of binaries, with the orbital angular momentum vector defining the axis of the nebula. Secondary symmetries in the nebulae, such as the point-symmetric knots in M1-91, could be due to other symmetries, such as the rotation axis of one of the individual stars or the polar axis of the accretion disk. 39 refs

  18. Cytoplasm localization of aminopeptidase M1 and its functional activity in root hair cells and BY-2 cells.

    Science.gov (United States)

    Lee, Ok Ran; Cho, Hyung-Taeg

    2012-12-01

    Aminopeptidase M1 (APM1) was the first M1 metallopeptidase family member identified in Arabidopsis, isolated by its affinity for the auxin transport inhibitor N-1-naphthylphthalamic acid (NPA). A loss-of-function mutation showed various developmental defects in cell division and auxin transport. APM1 was shown to be localized in endomembrane structures, the cytoplasm, and the plasma membrane. These previous results suggested that APM1 has diverse functional roles in different cell and tissue types. Here we report that APM1 localized to the cytoplasm, and its over-expression in the root hair cell caused longer root hair phenotypes. Treatment of aminopeptidase inhibitors caused internalization of auxin efflux PIN-FORMED proteins in root hair cells and suppressed short root hair phenotype of PIN3 overexpression line (PIN3ox). APM1 also localized to the cytoplasm in tobacco BY-2 cells, its over-expression had little effect on auxin transport in these cells.

  19. Determination of aflatoxins B1 and M1 in animal feeds and liquid milk using thin layer chromatography

    International Nuclear Information System (INIS)

    Njue, W.; Gitu, L.; Kaberia, F.

    1996-01-01

    Animal feed samples were collected from feeding troughs and analysed for levels of aflatoxins B 1 , a toxic and carcinogenic mycotoxin. When aflatoxin B 1 is consumed by dairy cattle some of it is hydroxylated to form aflatoxin M 1 , which can appear in milk. Since aflatoxin M 1 , is also toxic and carcinogenic, it was determined in liquid milk. The determinations were carried out using thin-layer chromatography. Some of the feed samples were found to contain concentrations of aflatoxin B 1 that were above maximum tolerated values in foods and feeds in various countries. Brewers grain and used poultry feed contained 133.4 ppb, while the barley husks had a maximum value of 27.4 ppb. The details of the experimental results and analytical methods used are presented.(author)

  20. Cosméticos Contém 1g: um caso de empreendedorismo e inovação

    OpenAIRE

    Guimarães,Liliane de Oliveira; Cardoza,Guillermo

    2005-01-01

    Este caso de ensino descreve a fundação e a expansão da Contém 1g, uma empresa brasileira do setor de higiene pessoal, perfumaria e cosméticos. Fundada em 1984 como empresa têxtil, seu proprietário redirecionou o negócio e iniciou a produção de perfumes em 1994. A história empresarial da Contém 1g é marcada pelo lançamento de novos produtos e pela utilização, a partir de determinado momento, de um sistema híbrido de vendas: venda direta e franquia. A decisão de expandir o negócio é o ponto de...

  1. Tensor Analysis Reveals Distinct Population Structure that Parallels the Different Computational Roles of Areas M1 and V1.

    Science.gov (United States)

    Seely, Jeffrey S; Kaufman, Matthew T; Ryu, Stephen I; Shenoy, Krishna V; Cunningham, John P; Churchland, Mark M

    2016-11-01

    Cortical firing rates frequently display elaborate and heterogeneous temporal structure. One often wishes to compute quantitative summaries of such structure-a basic example is the frequency spectrum-and compare with model-based predictions. The advent of large-scale population recordings affords the opportunity to do so in new ways, with the hope of distinguishing between potential explanations for why responses vary with time. We introduce a method that assesses a basic but previously unexplored form of population-level structure: when data contain responses across multiple neurons, conditions, and times, they are naturally expressed as a third-order tensor. We examined tensor structure for multiple datasets from primary visual cortex (V1) and primary motor cortex (M1). All V1 datasets were 'simplest' (there were relatively few degrees of freedom) along the neuron mode, while all M1 datasets were simplest along the condition mode. These differences could not be inferred from surface-level response features. Formal considerations suggest why tensor structure might differ across modes. For idealized linear models, structure is simplest across the neuron mode when responses reflect external variables, and simplest across the condition mode when responses reflect population dynamics. This same pattern was present for existing models that seek to explain motor cortex responses. Critically, only dynamical models displayed tensor structure that agreed with the empirical M1 data. These results illustrate that tensor structure is a basic feature of the data. For M1 the tensor structure was compatible with only a subset of existing models.

  2. Enhancement of CD147 on M1 macrophages induces differentiation of Th17 cells in the lung interstitial fibrosis.

    Science.gov (United States)

    Geng, Jie-jie; Zhang, Kui; Chen, Li-na; Miao, Jin-lin; Yao, Meng; Ren, Ying; Fu, Zhi-guang; Chen, Zhi-nan; Zhu, Ping

    2014-09-01

    Lung interstitial fibrosis is a chronic lung disease, and few effective therapies are available to halt or reverse the progression of the disease. In murine and human lung fibrosis, the expression of CD147 is increased. However, the role of CD147 in lung fibrosis has not been identified, and it remains to be determined whether lung fibrosis would be improved by decreasing the expression of CD147. A murine bleomycin-induced lung interstitial fibrosis model was used in the experiments, and HAb18 mAbs and CsA were administered during the induction of lung fibrosis. In our study, we found that the HAb18 mAbs markedly reduced the collagen score and down-regulated M1 macrophages and Th17 cells. In vitro, flow cytometry analysis showed that M1 macrophages induced higher Th17 differentiation than M2 macrophages. After treatment with HAb18 mAbs or after reducing the expression of CD147 by lentivirus interference in M1 macrophages, the level of Th17 cells were significantly inhibited. In conclusion, HAb18 mAbs or CsA treatment ameliorates lung interstitial fibrosis. CD147 promoted M1 macrophage and induced the differentiation of Th17 cells in lung interstitial fibrosis, perhaps by regulating some cytokines such as IL-6, IL-1β, IL-12 and IL-23. These results indicated that CD147 may play an important role in the development of lung interstitial fibrosis. Copyright © 2014 Elsevier B.V. All rights reserved.

  3. Molybdenum emission from impurity-induced m= 1 snake-modes on the Alcator C-Mod tokamak

    Energy Technology Data Exchange (ETDEWEB)

    Delgado-Aparicio, L. [Princeton Plasma Physics Laboratory, Princeton, New Jersey 08540 (United States); MIT - Plasma Science and Fusion Center, Cambridge, Massachusetts 02139 (United States); Bitter, M.; Gates, D.; Hill, K.; Pablant, N. [Princeton Plasma Physics Laboratory, Princeton, New Jersey 08540 (United States); Granetz, R.; Reinke, M.; Podpaly, Y.; Rice, J. [MIT - Plasma Science and Fusion Center, Cambridge, Massachusetts 02139 (United States); Beiersdorfer, P. [Lawrence Livermore National Laboratory, Livermore, California 94550 (United States); Sugiyama, L. [MIT - Laboratory for Nuclear Science, Cambridge, Massachusetts 02139 (United States)

    2012-10-15

    A suite of novel high-resolution spectroscopic imaging diagnostics has facilitated the identification and localization of molybdenum impurities as the main species during the formation and lifetime of m= 1 impurity-induced snake-modes on Alcator C-Mod. Such measurements made it possible to infer, for the first time, the perturbed radiated power density profiles from which the impurity density can be deduced.

  4. Tensor Analysis Reveals Distinct Population Structure that Parallels the Different Computational Roles of Areas M1 and V1.

    Directory of Open Access Journals (Sweden)

    Jeffrey S Seely

    2016-11-01

    Full Text Available Cortical firing rates frequently display elaborate and heterogeneous temporal structure. One often wishes to compute quantitative summaries of such structure-a basic example is the frequency spectrum-and compare with model-based predictions. The advent of large-scale population recordings affords the opportunity to do so in new ways, with the hope of distinguishing between potential explanations for why responses vary with time. We introduce a method that assesses a basic but previously unexplored form of population-level structure: when data contain responses across multiple neurons, conditions, and times, they are naturally expressed as a third-order tensor. We examined tensor structure for multiple datasets from primary visual cortex (V1 and primary motor cortex (M1. All V1 datasets were 'simplest' (there were relatively few degrees of freedom along the neuron mode, while all M1 datasets were simplest along the condition mode. These differences could not be inferred from surface-level response features. Formal considerations suggest why tensor structure might differ across modes. For idealized linear models, structure is simplest across the neuron mode when responses reflect external variables, and simplest across the condition mode when responses reflect population dynamics. This same pattern was present for existing models that seek to explain motor cortex responses. Critically, only dynamical models displayed tensor structure that agreed with the empirical M1 data. These results illustrate that tensor structure is a basic feature of the data. For M1 the tensor structure was compatible with only a subset of existing models.

  5. Unexpected expansion of tRNA substrate recognition by the yeast m1G9 methyltransferase Trm10.

    Science.gov (United States)

    Swinehart, William E; Henderson, Jeremy C; Jackman, Jane E

    2013-08-01

    N-1 Methylation of the nearly invariant purine residue found at position 9 of tRNA is a nucleotide modification found in multiple tRNA species throughout Eukarya and Archaea. First discovered in Saccharomyces cerevisiae, the tRNA methyltransferase Trm10 is a highly conserved protein both necessary and sufficient to catalyze all known instances of m1G9 modification in yeast. Although there are 19 unique tRNA species that contain a G at position 9 in yeast, and whose fully modified sequence is known, only 9 of these tRNA species are modified with m1G9 in wild-type cells. The elements that allow Trm10 to distinguish between structurally similar tRNA species are not known, and sequences that are shared between all substrate or all nonsubstrate tRNAs have not been identified. Here, we demonstrate that the in vitro methylation activity of yeast Trm10 is not sufficient to explain the observed pattern of modification in vivo, as additional tRNA species are substrates for Trm10 m1G9 methyltransferase activity. Similarly, overexpression of Trm10 in yeast yields m1G9 containing tRNA species that are ordinarily unmodified in vivo. Thus, yeast Trm10 has a significantly broader tRNA substrate specificity than is suggested by the observed pattern of modification in wild-type yeast. These results may shed light onto the suggested involvement of Trm10 in other pathways in other organisms, particularly in higher eukaryotes that contain up to three different genes with sequence similarity to the single TRM10 gene in yeast, and where these other enzymes have been implicated in pathways beyond tRNA processing.

  6. Screening the Medicines for Malaria Venture "Malaria Box" against the Plasmodium falciparum aminopeptidases, M1, M17 and M18.

    Directory of Open Access Journals (Sweden)

    Alessandro Paiardini

    Full Text Available Malaria is a parasitic disease that remains a global health burden. The ability of the parasite to rapidly develop resistance to therapeutics drives an urgent need for the delivery of new drugs. The Medicines for Malaria Venture have compounds known for their antimalarial activity, but not necessarily the molecular targets. In this study, we assess the ability of the "MMV 400" compounds to inhibit the activity of three metalloaminopeptidases from Plasmodium falciparum, PfA-M1, PfA-M17 and PfM18 AAP. We have developed a multiplex assay system to allow rapid primary screening of compounds against all three metalloaminopeptidases, followed by detailed analysis of promising compounds. Our results show that there were no PfM18AAP inhibitors, whereas two moderate inhibitors of the neutral aminopeptidases PfA-M1 and PfA-M17 were identified. Further investigation through structure-activity relationship studies and molecular docking suggest that these compounds are competitive inhibitors with novel binding mechanisms, acting through either non-classical zinc coordination or independently of zinc binding altogether. Although it is unlikely that inhibition of PfA-M1 and/or PfA-M17 is the primary mechanism responsible for the antiplasmodial activity reported for these compounds, their detailed characterization, as presented in this work, pave the way for their further optimization as a novel class of dual PfA-M1/PfA-M17 inhibitors utilising non-classical zinc binding groups.

  7. Computational Modeling with Fluid-Structure Interaction of the Severe M1 Stenosis Before and After Stenting

    OpenAIRE

    Park, Soonchan; Lee, Sang-Wook; Lim, Ok Kyun; Min, Inki; Nguyen, Minhtuan; Ko, Young Bae; Yoon, Kyunghwan; Suh, Dae Chul

    2013-01-01

    Purpose Image-based computational models with fluid-structure interaction (FSI) can be used to perform plaque mechanical analysis in intracranial artery stenosis. We described a process in FSI study applied to symptomatic severe intracranial (M1) stenosis before and after stenting. Materials and Methods Reconstructed 3D angiography in STL format was transferred to Magics for smoothing of vessel surface and trimming of branch vessels and to HyperMesh for generating tetra volume mesh from trian...

  8. How well do we know the quantum numbers of possible anti p p → M1M2 states

    International Nuclear Information System (INIS)

    Lanou, R.E.

    1979-01-01

    Information is available to completely analyze the p anti p → ππ reaction, allowing more global, large-scale, phenomenological analyses which combine the two experimental data sets in an energy independent, amplitude analysis which also includes pion-nucleon data. It would appear from the preliminary analyses of p anti p → M 1 M 2 angular distributions and polarizations the T-region may indeed contain some very interesting activity

  9. Diarylheptanoids suppress proliferation of pancreatic cancer PANC-1 cells through modulating shh-Gli-FoxM1 pathway.

    Science.gov (United States)

    Dong, Guang-Zhi; Jeong, Ji Hye; Lee, Yu-Ih; Lee, So Yoon; Zhao, Hui-Yuan; Jeon, Raok; Lee, Hwa Jin; Ryu, Jae-Ha

    2017-04-01

    Pancreatic cancer is one of the leading causes of cancer, and it has the lowest 5-year survival rates. It is necessary to develop more potent anti-pancreatic cancer drugs to overcome the fast metastasis and resistance to surgery, radiotherapy, chemotherapy, and combinations of these. We have identified several diarylheptanoids as anti-pancreatic cancer agents from Alpinia officinarum (lesser galangal) and Alnus japonica. These diarylheptanoids suppressed cell proliferation and induced the cell cycle arrest of pancreatic cancer cells (PANC-1). Among them, the most potent compounds 1 and 7 inhibited the shh-Gli-FoxM1 pathway and their target gene expression in PANC-1 cells. Furthermore, they suppressed the expression of the cell cycle associated genes that were rescued by the overexpression of exogenous FoxM1. Taken together, (E)-7-(4-hydroxy-3-methoxyphenyl)-1-phenylhept-4-en-3-one (1) from Alpinia officinarum (lesser galangal) and platyphyllenone (7) from Alnus japonica inhibit PANC-1 cell proliferation by suppressing the shh-Gli-FoxM1 pathway, and they can be potential candidates for anti-pancreatic cancer drug development.

  10. Operation of TRR-1/M1 for 25 years and lessons learned in management of safety and safety culture

    International Nuclear Information System (INIS)

    Keinmeesuke, Sirichai

    2002-01-01

    The first Thai Research Reactor, TRR-1, was installed and put into operation in 1962. In 1975 the reactor was converted to a 2 MW TRIGA Mark III by replacing of the reactor core and the control system. The renamed TRR-1/M1 research reactor went critical again in November 1977. TRR-1/M1 has been operated safely for 25 years with its main utilization in research, isotope production and training. Safety management and safety culture have been implemented for 25 years both in the legislation level and the operation level. There was no nuclear incident and there were a few radiological incidents during the 25 years of operation of TRR-1/M1. The lessons learned from the incident events such as the release of N-16 and Ar-41, the release of radioactive Bromine gave valued opportunities to improve our operation procedure, safety procedure and safety culture. All type of activities with respect to safety culture such as individual awareness, commitment, motivation, supervision and responsibility have been seriously reviewed and being set as normal practices. (author)

  11. Genotype-phenotype correlations and expansion of the molecular spectrum of AP4M1-related hereditary spastic paraplegia

    Directory of Open Access Journals (Sweden)

    Conceição Bettencourt

    2017-11-01

    Full Text Available Abstract Background Autosomal recessive hereditary spastic paraplegia (HSP due to AP4M1 mutations is a very rare neurodevelopmental disorder reported for only a few patients. Methods We investigated a Greek HSP family using whole exome sequencing (WES. Results A novel AP4M1A frameshift insertion, and a very rare missense variant were identified in all three affected siblings in the compound heterozygous state (p.V174fs and p.C319R; the unaffected parents were carriers of only one variant. Patients were affected with a combination of: (a febrile seizures with onset in the first year of life (followed by epileptic non-febrile seizures; (b distinctive facial appearance (e.g., coarse features, bulbous nose and hypomimia; (c developmental delay and intellectual disability; (d early-onset spastic weakness of the lower limbs; and (e cerebellar hypoplasia/atrophy on brain MRI. Conclusions We review genotype-phenotype correlations and discuss clinical overlaps between different AP4-related diseases. The AP4M1 belongs to a complex that mediates vesicle trafficking of glutamate receptors, being likely involved in brain development and neurotransmission.

  12. CTX-M-1 β-lactamase expression in Escherichia coli is dependent on cefotaxime concentration, growth phase and gene location

    DEFF Research Database (Denmark)

    Kjeldsen, Thea S. B.; Overgaard, Martin; Nielsen, Søren S.

    2015-01-01

    blaCTX-M-1 mRNA expression and CTX-M-1 protein levels were dependent on cefotaxime concentration, growth phase and gene location. These results provide insight into the expression of cephalosporin resistance in CTX-M-1-producing E. coli, improving our understanding of the relationship between ant...

  13. Influenza A Virus NS1 Protein Promotes Efficient Nuclear Export of Unspliced Viral M1 mRNA.

    Science.gov (United States)

    Pereira, Carina F; Read, Eliot K C; Wise, Helen M; Amorim, Maria J; Digard, Paul

    2017-08-01

    Influenza A virus mRNAs are transcribed by the viral RNA-dependent RNA polymerase in the cell nucleus before being exported to the cytoplasm for translation. Segment 7 produces two major transcripts: an unspliced mRNA that encodes the M1 matrix protein and a spliced transcript that encodes the M2 ion channel. Export of both mRNAs is dependent on the cellular NXF1/TAP pathway, but it is unclear how they are recruited to the export machinery or how the intron-containing but unspliced M1 mRNA bypasses the normal quality-control checkpoints. Using fluorescent in situ hybridization to monitor segment 7 mRNA localization, we found that cytoplasmic accumulation of unspliced M1 mRNA was inefficient in the absence of NS1, both in the context of segment 7 RNPs reconstituted by plasmid transfection and in mutant virus-infected cells. This effect was independent of any major effect on steady-state levels of segment 7 mRNA or splicing but corresponded to a ∼5-fold reduction in the accumulation of M1. A similar defect in intronless hemagglutinin (HA) mRNA nuclear export was seen with an NS1 mutant virus. Efficient export of M1 mRNA required both an intact NS1 RNA-binding domain and effector domain. Furthermore, while wild-type NS1 interacted with cellular NXF1 and also increased the interaction of segment 7 mRNA with NXF1, mutant NS1 polypeptides unable to promote mRNA export did neither. Thus, we propose that NS1 facilitates late viral gene expression by acting as an adaptor between viral mRNAs and the cellular nuclear export machinery to promote their nuclear export. IMPORTANCE Influenza A virus is a major pathogen of a wide variety of mammalian and avian species that threatens public health and food security. A fuller understanding of the virus life cycle is important to aid control strategies. The virus has a small genome that encodes relatively few proteins that are often multifunctional. Here, we characterize a new function for the NS1 protein, showing that, as well as

  14. Electrical dipole polarizability and spin M1 strength from {sup 48}Ca(p,p') data under 0; Elektrische Dipol-Polarisierbarkeit und Spin-M1-Staerke aus {sup 48}Ca(p,p')-Daten unter 0

    Energy Technology Data Exchange (ETDEWEB)

    Birkhan, Jonny Hubertus

    2016-07-01

    In this thesis, proton scattering data on the nucleus {sup 48}Ca at very forward angles had been analysed. The data stem from a measurement campaign which was launched at the Research Centre of Nuclear Physics at Osaka, Japan, in the past. One of the two objectives of this analysis was to extract a value for the static electric dipole polarisability from the isovector giant dipole resonance (IVGDR). The second objective was to extract the total electromagnetic M1 strength B(M1) of the spin-flip transition which excites the prominent 1{sup +} state at an excitation energy of E{sub x}=10.22 MeV. The polarisability was calculated from the distribution of photo-absorption cross sections within an energy range from E{sub x}=11 MeV to E{sub x}=26 MeV. The photo-absorption cross sections had been deduced from the distribution of E1 cross sections by the method of virtual photons. For this purpose the experimental cross sections had been deconvoluted by a multipole deconvolution into an E1 part and a background part. Then, the best estimate of the polarisability is given by α{sub D}=(1.36±0.14) fm{sup 3}. If a E3 model was included into the multipole decomposition of the (p,p') data the result increased up to α{sub D}=(1.50±0.09) fm{sup 3}. The deviation between these two results is mainly due to the fact that the multipole decomposition is very sensitive on the background function. Assuming that the the IVGDR of the nuclei {sup 48}Ca and {sup 40}Ca have approximately the same structure, estimates for the polarisability of the nucleus {sup 48}Ca could be drawn from {sup 40}Ca(γ,abs) data. Additionally, data from a {sup 48}Ca(e,e'n) measurement were used to estimate the polarisability of the nucleus {sup 48}Ca. Its polarisability seems to fall within the range of α{sub D}=(1.50±0.09) fm{sup 3} and α{sub D}=(1.69±0.03) fm{sup 3}. Beside this, it could be shown by the {sup 40}Ca data that a significant contribution to the polarisability has to be expected

  15. ApolipoproteinA1-75 G/A (M1- polymorphism and Lipoprotein(a; Anti- vs. Pro-Atherogenic properties

    Directory of Open Access Journals (Sweden)

    Ranganath L

    2007-08-01

    Full Text Available Abstract Background ApolipoproteinA1(apoA1 is the major apoprotein constituent of high-density-lipoprotein(HDL. The relationship of apoA1 -75 bp(M1- allele polymorphism with lipoprotein phenotype and cardiovascular diseae (CVD remain unclear. Overnight fasting blood samples were collected from a cohort of high-risk Omani population, 90 non-diabetic subjects and 149 type 2 diabetes mellitus (T2DM subjects for genotype and phenotype studies. Results The M1+ and M1- alleles frequencies were 0.808 and 0.192 for M1+ and M1-, respectively, comparable to the frequency of apoA1 (M1+ and M1- amongst a healthy Omani population, 0.788 and 0.212, respectively. The frequencies of the hetero- and homozygous subjects for the MspI polymorphism at -75 (M1- of the apoA1 gene were in Hardy-Weinberg equilibrium. The mean Lp(a concentration was significantly higher(P = 0.02 in subjects carrying M1- allele compared to M1+ allele of the APOA1 gene with an odd ratio of 2.3(95% CI, 1.13–14.3, irrespective of gender and the diabetic status. Conclusion ApolipoproteinA1-75 G/A (M1- polymorphism is relatively common and is positively associated with Lp(a and therefore, may confer a potential risk for cardiovascular disease (CVD.

  16. miR-148a-3p Mediates Notch Signaling to Promote the Differentiation and M1 Activation of Macrophages

    Directory of Open Access Journals (Sweden)

    Fei Huang

    2017-10-01

    Full Text Available The Notch pathway plays critical roles in the differentiation and polarized activation of macrophages; however, the downstream molecular mechanisms underlying Notch activity in macrophages remain elusive. Our previous study has identified a group of microRNAs that mediate Notch signaling to regulate macrophage activation and tumor-associated macrophages (TAMs. In this study, we demonstrated that miR-148a-3p functions as a novel downstream molecule of Notch signaling to promote the differentiation of monocytes into macrophages in the presence of granulocyte macrophage colony-stimulating factor (GM-CSF. Meanwhile, miR-148a-3p promoted M1 and inhibited M2 polarization of macrophages upon Notch activation. Macrophages overexpressing miR-148a-3p exhibited enhanced ability to engulf and kill bacteria, which was mediated by excessive production of reactive oxygen species (ROS. Further studies using reporter assay and Western blotting identified Pten as a direct target gene of miR-148a-3p in macrophages. Macrophages overexpressing miR-148a-3p increased their ROS production through the PTEN/AKT pathway, likely to defend against bacterial invasion. Moreover, miR-148a-3p also enhanced M1 macrophage polarization and pro-inflammatory responses through PTEN/AKT-mediated upregulation of NF-κB signaling. In summary, our data establish a novel molecular mechanism by which Notch signaling promotes monocyte differentiation and M1 macrophage activation through miR-148a-3p, and suggest that miR-148a-3p-modified monocytes or macrophages are potential new tools for the treatment of inflammation-related diseases.

  17. NDRG2 promoted secreted miR-375 in microvesicles shed from M1 microglia, which induced neuron damage.

    Science.gov (United States)

    Tang, Li-li; Wu, Yuan-bo; Fang, Chuan-qin; Qu, Ping; Gao, Zong-liang

    2016-01-15

    Microglia microvesicles (MVs) has shown to have significant biological functions under normal conditions. A diversity of miRNAs is involved in neuronal development, survival, function, and plasticity, but the exact functional role of NDRG2 and secreted miR-375 in MVs in neuron damage is poorly understood. We investigated the effect of NDRG2 and secreted miR-375 in MVs shed from M1 microglia on neuron damage. Expression of Nos2, Arg-1, miR-375, syntaxin-1A, NDRG2 and Pdk 1 were evaluated using RT-PCR or western blotting. Cell viability of N2A neuron was quantified by a MTT assay. Microglia can be polarized into different functional phenotypes. Expression of NDRG2 and Nos2 were significantly increased by LPS treatment on N9 cells, whereas treatment with IL-4 dramatically suppressed the expression of NDRG2 and remarkably elevated expression of Arg-1. Besides, MVs shed from LPS-treated N9 microglia significantly inhibited cell viability of N2A neurons and expression of syntaxin-1A, and NDRG2 interference reversed the up-regulated miR-375 in LPS-treated N9 microglia and MVs shed from LPS-treated N9 cells. Furthermore, NDRG2 could modulate miR-375 expression in N9 microglia and MVs. And miR-375 inhibitor remarkably elevated Pdk1 expression in N2A neurons. Finally, miR-375 inhibitor could reverse suppression effect of NDRG2 overexpression on cell viability of N2A neurons and expression of syntaxin-1A. Our results demonstrated that NDRG2 promoted secreted miR-375 in microvesicles shed from M1 microglia, which induced neuron damage. The suppression of NDRG2 and secreted miR-375 in MVs shed from M1 microglia may be potential targets for alleviation of neuron damage. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Use of 3-(4-hydroxyphenyl)propionic acid as electron donating compound in a potentiometric aflatoxin M1-immunosensor

    International Nuclear Information System (INIS)

    Rameil, Steffen; Schubert, Peter; Grundmann, Peter; Dietrich, Richard; Maertlbauer, Erwin

    2010-01-01

    We developed a potentiometric aflatoxin M 1 -immunosensor which utilizes 3-(4-hydroxyphenyl)propionic acid (p-HPPA) as electron donating compound for horseradish peroxidase (HRP; EC 1.11.1.7). The assay system consists of a polypyrrole-surface-working electrode coated with a polyclonal anti-M 1 antibody (pAb-AFM 1 ), a Ag/AgCl reference electrode and a HRP-aflatoxin B 1 conjugate (HRP-AFB 1 conjugate). To optimize the potentiometric measuring system p-HPPA as well as related compounds serving as electron donating compounds were compared. Also the influence of different buffer systems, varying pH and substrate concentrations on signal intensity was investigated. Our results suggest that reaction conditions that favor the formation of Pummerer's type ketones lead to an increase in signal intensity rather than formation of fluorescent dye. Comparison with commercial ready-to-use HRP electron donating compounds such as 2,2'-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt (ABTS), o-phenylenediamine (OPD) or 3,3',5,5'-tetramethylbenzidine (TMB) showed that only 34%, 77% and 49% of the signal intensity of p-HPPA were reached, respectively. The optimized assay had a detection limit of 40 pg mL -1 and allowed detection of 500 pg mL -1 (FDA action limit) aflatoxin M 1 (AFM 1 ) in pasteurized milk and UHT-milk containing 0.3-3.8% fat within 10 min without any sample treatment. The working range was between 250 and 2000 pg mL -1 AFM 1 .

  19. Transient solution of an M/M/1 vacation queue with a waiting server and impatient customers

    Directory of Open Access Journals (Sweden)

    Sherif I. Ammar

    2017-07-01

    Full Text Available Recently, Ammar [1] has discussed the transient behavior of a multiple vacations queue with impatient customers. In this paper, a similar technique is used to derive a new elegant explicit solution for an M/M/1 vacation queue with impatient customers and a waiting server, where the server is allowed to take a vacation whenever the system is empty after waiting for a random period of time. If the server does not return from the vacation before the expiry of the customer impatience time, the customer abandons the system forever. Moreover, the formulas of mean and variance expressed in terms of the obtained possibilities for this model.

  20. Muscarinic M1 receptor inhibition reduces gastroduodenal bicarbonate secretion and promotes gastric prostaglandin E2 synthesis in healthy volunteers

    DEFF Research Database (Denmark)

    Mertz-Nielsen, A; Hillingsø, Jens; Eskerod, O

    1995-01-01

    stimulated gastric and basal duodenal bicarbonate secretion by about 50% (p basal and vagally stimulated PGE2 output increased significantly (p ...The selective muscarinic M1 receptor antagonist, pirenzepine, considerably stimulates duodenal mucosal bicarbonate secretion in the rat and increases gastric luminal release of prostaglandin E2 (PGE2) in humans. This study, therefore, looked at the effect of pirenzepine on bicarbonate secretion...... sham feeding and acid exposure (HCl 0.1 M; 20 ml; 5 min) of the duodenal bulb increased mucosal bicarbonate secretion from 191 (14) mumol/cm x h to 266 (27) mumol/cm x h (p basal and vagally...

  1. Involvement of Striatal Cholinergic Interneurons and M1 and M4 Muscarinic Receptors in Motor Symptoms of Parkinson's Disease.

    Science.gov (United States)

    Ztaou, Samira; Maurice, Nicolas; Camon, Jeremy; Guiraudie-Capraz, Gaëlle; Kerkerian-Le Goff, Lydia; Beurrier, Corinne; Liberge, Martine; Amalric, Marianne

    2016-08-31

    Over the last decade, striatal cholinergic interneurons (ChIs) have reemerged as key actors in the pathophysiology of basal-ganglia-related movement disorders. However, the mechanisms involved are still unclear. In this study, we address the role of ChI activity in the expression of parkinsonian-like motor deficits in a unilateral nigrostriatal 6-hydroxydopamine (6-OHDA) lesion model using optogenetic and pharmacological approaches. Dorsal striatal photoinhibition of ChIs in lesioned ChAT(cre/cre) mice expressing halorhodopsin in ChIs reduces akinesia, bradykinesia, and sensorimotor neglect. Muscarinic acetylcholine receptor (mAChR) blockade by scopolamine produces similar anti-parkinsonian effects. To decipher which of the mAChR subtypes provides these beneficial effects, systemic and intrastriatal administration of the selective M1 and M4 mAChR antagonists telenzepine and tropicamide, respectively, were tested in the same model of Parkinson's disease. The two compounds alleviate 6-OHDA lesion-induced motor deficits. Telenzepine produces its beneficial effects by blocking postsynaptic M1 mAChRs expressed on medium spiny neurons (MSNs) at the origin of the indirect striatopallidal and direct striatonigral pathways. The anti-parkinsonian effects of tropicamide were almost completely abolished in mutant lesioned mice that lack M4 mAChRs specifically in dopamine D1-receptor-expressing neurons, suggesting that postsynaptic M4 mAChRs expressed on direct MSNs mediate the antiakinetic action of tropicamide. The present results show that altered cholinergic transmission via M1 and M4 mAChRs of the dorsal striatum plays a pivotal role in the occurrence of motor symptoms in Parkinson's disease. The striatum, where dopaminergic and cholinergic systems interact, is the pivotal structure of basal ganglia involved in pathophysiological changes underlying Parkinson's disease. Here, using optogenetic and pharmacological approaches, we investigated the involvement of striatal

  2. DFT study on oxidation of HS(CH2) m SH ( m = 1-8) in oxidative desulfurization

    Science.gov (United States)

    Song, Y. Z.; Song, J. J.; Zhao, T. T.; Chen, C. Y.; He, M.; Du, J.

    2016-06-01

    Density functional theory was employed for calculation of HS(CH2) m SH ( m = 1-8) and its derivatives at B3LYP method at 6-31++g ( d, p) level. Using eigenvalues of LUMO and HOMO for HS(CH2) m SH, the standard electrode potentials were estimated by a stepwise multiple regression techniques (MLR), and obtained as E° = 1.500 + 7.167 × 10-3 HOMO-0.229 LUMO with high correlation coefficients of 0.973 and F values of 43.973.

  3. The muscarinic M1/M4 receptor agonist xanomeline exhibits antipsychotic-like activity in Cebus apella monkeys

    DEFF Research Database (Denmark)

    Andersen, Maibritt B; Fink-Jensen, Anders; Peacock, Linda

    2003-01-01

    (EPS) at therapeutically relevant doses. In the present study, we examined whether the xanomeline-induced functional dopamine antagonism found in rodent studies could also be observed in nonhuman primates. In addition, we studied whether the lack of EPS observed in rodents also applies to primates......Xanomeline is a muscarinic M(1)/M(4) preferring receptor agonist with little or no affinity for dopamine receptors. The compound reduces psychotic-like symptoms in patients with Alzheimer's disease and exhibits an antipsychotic-like profile in rodents without inducing extrapyramidal side effects...

  4. Influence of the projection of BCS functions on the M1 and E2 transitions in rare earths

    International Nuclear Information System (INIS)

    Fellah, M.; Hammann, T.F.

    1975-01-01

    E2 and M1 transition probabilities for odd-mass rare earth nuclei, have been calculated using both the usual BCS wave functions and the strict particle conserving, projected BCS functions. The blocking effect has been exactly and systematically taken into account. The influence of the Coriolis interaction has been studied using the first order perturbation theory. Allowance has been made for the β and γ vibrations. The unphysical effects, due to particle fluctuation in the BCS theory, are not always negligible, but are in most cases, less important than the Coriolis effect [fr

  5. Heterozygous M1V variant of ELA-2 gene mutation associated with G-CSF refractory severe congenital neutropenia.

    Science.gov (United States)

    Setty, Bhuvana A; Yeager, Nicholas D; Bajwa, Rajinder P

    2011-09-01

    Severe congenital neutropenia is an autosomal recessive disorder characterized by maturation arrest at the promyelocyte/myelocyte phase in the bone marrow, absolute neutrophil count ELA-2 have been described. We report the case of a premature male infant with congenital neutropenia, associated with multiple infections, refractory to treatment with granulocyte colony stimulating factor who subsequently underwent matched sibling donor stem-cell transplant. He was found to be heterozygous for the M1V variant of the ELA-2 gene that we postulate to be causative for his severe neutropenia Copyright © 2011 Wiley-Liss, Inc.

  6. Safety Analysis Report for Packaging (SARP): USA/9507/BLF (ERDA--AL), Model AL-M1

    International Nuclear Information System (INIS)

    Watkins, R.A.; Bertram, R.E.; Blauvelt, R.K.; Edling, D.A.; Flanagan, T.M.; Griffin, J.F.; Rhinehammer, T.B.

    1977-01-01

    The SARP includes structural integrity, thermal resistance, radiation shielding and radiological safety, nuclear criticality safety, and quality control of three insulated drum shipping containers identified as USA/9507/BLF (ERDA-AL), also called AL-M1, configurations 1, 3, and 5. Complete physical and technical descriptions of the packages are presented. Each package consists of an inner container centered within an insulated steel drum. The contents are plutonium-239 and uranium-235 in configurations-1 and -3. The configuration-5 package is intended for shipment of up to 100,000 Ci of tritiated water immobilized on a sorbent such as molecular sieve

  7. Study of gamma-ray induced variability on F1M1-F3M3 distant tomato hybrids

    International Nuclear Information System (INIS)

    Siromeatnicov, Iulia; Cotenco, Eugenia; Ciobanu, Renata

    2013-01-01

    The outcome of the evaluation of the gamma radiation's action, the growth and development tomato plant has shown that the coefficient of variation of plant height character is on the rise with increasing doses of gamma radiation. The hybrid combination F 1 M 1 (L.hpriz.1998) irradiated with dose 150 Gy variant presented superior value a towards scrutiny for plant height of the characters, number of flowers and fruits per bunch, number of fruits per plant and fruit mass of. The character F 2 M 2 generation plant height registered diminished value compared to F 1 M 1 generation. The highest value was recorded at the hybrid combination F 2 M 2 L.hpriz.1998 200 Gy treated dose. The evaluation research has highlighted that at the doses 100 Gy, 150 Gy, 200 Gy, have confirmed an increase in characters of reproductive system: the number of flowers and fruits per bunch, number of fruits per plant, fruit mass and reduction of the characters waist and height of placing of the first inflorescences plant. Similar aspects with some differences as low as hybrid combination Lhpi1998 in relation to the radiation doses used under study were confirmed in the case F 3 M 3 . (authors)

  8. A Study on the Occurrence of Aflatoxin M1 in Raw and Pasteurized Milk Produced in Rafsanjan, Iran

    Directory of Open Access Journals (Sweden)

    FaAkrami Mohajeri Akrami Mohajeri

    2015-12-01

    Full Text Available Introduction: Aflatoxins, known as causative factors of hepatic and extra-hepatic carcinogenesis within humans, are extremely teratogenic, mutagenic, toxic, and carcinogenic compounds. Materials & Methods: This study was undertaken to determine the occurrence of aflatoxin M1 (AFM1 in 40 raw milk and 47 pasteurized milk samples collected during spring and winter. In order to analyze the samples, the Enzyme-linked Immunosorbent Assay (ELISA procedure was used. The statistical methods used in this study were based on normal confidence intervals and analysis of variance (ANOVA. Results: Aflatoxin M1 was detected in 97.5% of the raw milk ranging from 6.52 to 68.17 ng/l and 95.7% of the pasteurized milk, ranging from 0.8 to 58.13 ng/l. Toxin levels in 10% of the raw milk and 2.1% of the pasteurized milk samples exceeded the Iranian national standard limit i.e. 50 ng/l.  Due to seasonal variations, mean concentration of AFM1 in the samples collected in winter was significantly (P < 0.03 higher than those collected in the summer. Conclusion: Large amount of AFM1 in milk samples might be a potential hazard for the public health. Reducing the levels of AFB1 in animal feedstuffs can be regarded as the initial step to control the transfer of AFM1 to humans.

  9. Effect of Gamma Irradiation on Morphological Traits in M1 Generation of Kenaf (Hibiscus cannabinus L.) V36 Variety

    International Nuclear Information System (INIS)

    Faiz Ahmad; Mohd Zulmadi Sani; Mustapha Akil

    2016-01-01

    Kenaf (Hibiscus cannabinus L.) is one of the world most economically important fiber crops particularly in Asian-Pacific region. Mutation induction is a method to increase genetic divergence associated with selection, recombination, or a combination of these approaches in plant breeding. The present study was aimed to evaluate the effects of selected gamma irradiation doses (200 Gy and 300 Gy) on the kenaf morphological traits in M1 generation. Irradiated and non-irradiated of kenaf seed from V36 variety were planted in the field at Beseri, Perlis. Soil condition at the field, morphological changes and 10 morphological traits of irradiated plants were observed and evaluated against the controls. Cluster analysis result on M1 progenies showed that the mutation observed were classified into eight genotypic groups. The first two components from principal component analysis explained about 77.99 % of variation. Number of seed per pod, weight of seed per plant and dry stem biomass play important role to explain the variation since they showed positive correlated values for the first component analysis. Thus, this study is important in determining the effectiveness of these doses in generating mutations. In addition, it can also be used to generate a new source of germplasm in kenaf with enhanced quality traits such as high yielding and high fiber content. (author)

  10. Preliminary validation of computational model for neutron flux prediction of Thai Research Reactor (TRR-1/M1)

    Science.gov (United States)

    Sabaibang, S.; Lekchaum, S.; Tipayakul, C.

    2015-05-01

    This study is a part of an on-going work to develop a computational model of Thai Research Reactor (TRR-1/M1) which is capable of accurately predicting the neutron flux level and spectrum. The computational model was created by MCNPX program and the CT (Central Thimble) in-core irradiation facility was selected as the location for validation. The comparison was performed with the typical flux measurement method routinely practiced at TRR-1/M1, that is, the foil activation technique. In this technique, gold foil is irradiated for a certain period of time and the activity of the irradiated target is measured to derive the thermal neutron flux. Additionally, the flux measurement with SPND (self-powered neutron detector) was also performed for comparison. The thermal neutron flux from the MCNPX simulation was found to be 1.79×1013 neutron/cm2s while that from the foil activation measurement was 4.68×1013 neutron/cm2s. On the other hand, the thermal neutron flux from the measurement using SPND was 2.47×1013 neutron/cm2s. An assessment of the differences among the three methods was done. The difference of the MCNPX with the foil activation technique was found to be 67.8% and the difference of the MCNPX with the SPND was found to be 27.8%.

  11. Classification of M1/M2-polarized human macrophages by label-free hyperspectral reflectance confocal microscopy and multivariate analysis.

    Science.gov (United States)

    Bertani, Francesca R; Mozetic, Pamela; Fioramonti, Marco; Iuliani, Michele; Ribelli, Giulia; Pantano, Francesco; Santini, Daniele; Tonini, Giuseppe; Trombetta, Marcella; Businaro, Luca; Selci, Stefano; Rainer, Alberto

    2017-08-21

    The possibility of detecting and classifying living cells in a label-free and non-invasive manner holds significant theranostic potential. In this work, Hyperspectral Imaging (HSI) has been successfully applied to the analysis of macrophagic polarization, given its central role in several pathological settings, including the regulation of tumour microenvironment. Human monocyte derived macrophages have been investigated using hyperspectral reflectance confocal microscopy, and hyperspectral datasets have been analysed in terms of M1 vs. M2 polarization by Principal Components Analysis (PCA). Following PCA, Linear Discriminant Analysis has been implemented for semi-automatic classification of macrophagic polarization from HSI data. Our results confirm the possibility to perform single-cell-level in vitro classification of M1 vs. M2 macrophages in a non-invasive and label-free manner with a high accuracy (above 98% for cells deriving from the same donor), supporting the idea of applying the technique to the study of complex interacting cellular systems, such in the case of tumour-immunity in vitro models.

  12. Co-expression of two subtypes of melatonin receptor on rat M1-type intrinsically photosensitive retinal ganglion cells.

    Directory of Open Access Journals (Sweden)

    Wen-Long Sheng

    Full Text Available Intrinsically photosensitive retinal ganglion cells (ipRGCs are involved in circadian and other non-image forming visual responses. An open question is whether the activity of these neurons may also be under the regulation mediated by the neurohormone melatonin. In the present work, by double-staining immunohistochemical technique, we studied the expression of MT1 and MT2, two known subtypes of mammalian melatonin receptors, in rat ipRGCs. A single subset of retinal ganglion cells labeled by the specific antibody against melanopsin exhibited the morphology typical of M1-type ipRGCs. Immunoreactivity for both MT1 and MT2 receptors was clearly seen in the cytoplasm of all labeled ipRGCs, indicating that these two receptors were co-expressed in each of these neurons. Furthermore, labeling for both the receptors were found in neonatal M1 cells as early as the day of birth. It is therefore highly plausible that retinal melatonin may directly modulate the activity of ipRGCs, thus regulating non-image forming visual functions.

  13. Studies on the structures of the Tm, Sj, M1, Can, Sext and Hu blood group antigens.

    Science.gov (United States)

    Dahr, W; Knuppertz, G; Beyreuther, K; Moulds, J J; Moulds, M; Wilkinson, S; Capon, C; Fournet, B; Issitt, P D

    1991-08-01

    The Glycophorins (GPs = sialoglycoproteins) in erythrocyte membranes from various Black individuals, some of which exhibit the M1, Can, Sj, Tm, Sext and/or Hu antigens, and several Caucasian donors, including pooled fetal red cells, were studied. Using agglutination inhibition assays with GP fractions, GP fragments and chemically modified GPs as well as trypsin treatment of intact red cells, the antigens defined by anti-M1, anti-M+M1, anti-Can and anti-Tm sera were found to be located on the N-terminal tryptic peptide (T2, residues 1-31) of the major GP (GP A = MN sialoglycoprotein). Evidence was obtained that the N-terminal amino-acid residue, NeuNAc and/or (a) different sugar residue(s) are involved in the antigens. Amino-acid sequence and composition analyses excluded an amino-acid exchange within the N-terminal region (residues 1-31) of GP A. Carbohydrate analyses revealed the attachment of GlcNAc residues (up to about five, dependent on the strength of the above-mentioned antigens) to O-glycosidically linked oligosaccharides within the N-terminal portion (residues 1-31) of GP A. As judged from the carbohydrate compositions of peptides, the alteration of the O-glycosidic oligosaccharides is associated with a slight increase of the Gal and Fuc contents and a slight decrease of the NeuNAc level. Analyses of small, secondary cyanogen bromide and V8 proteinase peptides from the N-terminal region of GP A from Blacks, Caucasians and Caucasian fetal cells suggest that the variable attachment of small quantities of GlcNAc (about 0.03 to about 0.2 residues per peptide molecule) accounts, at least in part, for the polymorphisms detected by anti-Can and the original anti-Tm (serum Sheerin). Remarkably, the GlcNAc-containing O-glycosidic oligosaccharides occur only in small quantities, or not all at, within the positions 32-61 of GP A and the glycosylated domains of GP B and GP C.(ABSTRACT TRUNCATED AT 400 WORDS)

  14. Simulations of the instability of the m=1 self-shielding diocotron mode in finite-length nonneutral plasmas

    International Nuclear Information System (INIS)

    Mason, Grant W.; Spencer, Ross L.

    2002-01-01

    The 'self-shielding' m=1 diocotron mode in Malmberg-Penning traps has been known for over a decade to be unstable for finite length nonneutral plasmas with hollow density profiles. Early theoretical efforts were unsuccessful in accounting for the exponential growth and/or the magnitude of the growth rate. Recent theoretical work has sought to resolve the discrepancy either as a consequence of the shape of the plasma ends or as a kinetic effect resulting from a modified distribution function as a consequence of the protocol used to form the hollow profiles in experiments. We have investigated both of these finite length mechanisms in selected test cases using a three-dimensional particle-in-cell code that allows realistic treatment of shape and kinetic effects. We find that a persistent discrepancy of a factor of 2-3 remains between simulation and experimental values of the growth rate

  15. Pricing in M/M/1 queues when cost of waiting in queue differs from cost of waiting in service

    Directory of Open Access Journals (Sweden)

    Görkem Sarıyer

    2016-11-01

    Full Text Available Service providers can adjust the entrance price to the state of the demand in real life service systems where the customers' decision to receive the service, is based on this price, state of demand and other system parameters. We analyzed service provider's short and long term pricing problems in unobservable M/M/1 queues having the rational customers, where, for customers, the unit cost of waiting in the queue is higher than unit cost of waiting in the service. We showed that waiting in the queue has a clear negative effect on customers’ utilities, hence the service provider's price values. We also showed that, in the short term, monopolistic pricing is optimal for congested systems with high server utilization levels, whereas in the long term, market capturing pricing is more profitable.

  16. Internal helical modes with m > 1 in a tokamak with a small shear and high plasma pressure

    International Nuclear Information System (INIS)

    Mikha lovskij, A.B.; Aburdzhaniya, G.D.; Krymskij, A.M.

    1979-01-01

    Internal helical modes with m>1 in a circular cross-section tokamak with a small shear and large value of the parameter β (β is the ratio between the mean plasma pressure and the mean pressure of the poloidal magnetic field) are investigated. The equations obtained are used to study the destabilizing effects leading to helical instabilities. The role of destabilizing effects is regarded both in local and in a nonlocal approximations on the assumption that the radial plasma pressure is distributed parabolically and that the radial current distribution is also parabolic though slightly varying. It has been established that the profiling of current may lead to the tokamak plasma stability with respect to the modes under investigation. A tokamak with a small shear has been shown to be more stable relative to these modes than that with a large shear

  17. Status of prompt gamma neutron activation analysis (PGAA) at TRR-1/M1 (Thai Research Reactor-1/Modified 1)

    International Nuclear Information System (INIS)

    Asvavijnijkulchai, Chanchai; Dharmavanij, Wanchai; Siangsanan, Pariwat; Ratanathongchai, Wichian; Chongkum, Somporn

    1999-01-01

    The first prompt gamma activation analysis (PGAA) was designed, constructed and installed at a 6 inch diameter neutron beam port of the Thai Research Reactor-1/Modified 1 (TRR-1/M1) since 1989. Beam characteristic were made by Gd foil irradiation, X-ray film exposing and densitometry scanning consequently. The thermal neutron flux at sample position was measured by Au foil activation, and was about 1 x 10 7 n.cm 2 .sec -1 at 700 kW operating power. The experiments have been conducted successfully. In 1998, the PGAA facility has been developed for the reactor operating power at 1.2 MW. The new PGAA system, e.g., beam shutter, gamma collimator and biological shields have been designed to reduce the leakage of neutrons and gamma radiation to the acceptance levels in accordance with the International Commission on Radiation Protection Publication 60 (ICRP 60). The construction and installation will be completed in April 1999. (author)

  18. Pancreas of C57 black mice after long-term space flight (Bion-M1 Space Mission).

    Science.gov (United States)

    Proshchina, A E; Krivova, Y S; Saveliev, S C

    2015-11-01

    In this study, we analysed the pancreases of C57BL/6N mice in order to estimate the effects of long-term space flights. Mice were flown aboard the Bion-M1 biosatellite, or remained on ground in the control experiment that replicated environmental and housing conditions in the spacecraft. Vivarium control group was used to account for housing effects. Each of the groups included mice designated for recovery studies. Mice pancreases were dissected for histological and immunohistochemical examinations. Using a morphometry and statistical analysis, a strong correlation between the mean islet size and the mean body weight was revealed in all groups. Therefore, we propose that hypokinesia and an increase in nutrition play an important role in alterations of the endocrine pancreas, both in space flight and terrestrial conditions. Copyright © 2015 The Committee on Space Research (COSPAR). Published by Elsevier Ltd. All rights reserved.

  19. E 2 decay strength of the M 1 scissors mode of 156Gd and its first excited rotational state

    Science.gov (United States)

    Beck, T.; Beller, J.; Pietralla, N.; Bhike, M.; Birkhan, J.; Derya, V.; Gayer, U.; Hennig, A.; Isaak, J.; Löher, B.; Ponomarev, V. Yu.; Richter, A.; Romig, C.; Savran, D.; Scheck, M.; Tornow, W.; Werner, V.; Zilges, A.; Zweidinger, M.

    2017-05-01

    The E 2 /M 1 multipole mixing ratio δ1 →2 of the 1sc+→21+ γ -ray decay in 156Gd and hence the isovector E 2 transition rate of the scissors mode of a well-deformed rotational nucleus has been measured for the first time. It has been obtained from the angular distribution of an artificial quasimonochromatic linearly polarized γ -ray beam of energy 3.07(6) MeV scattered inelastically off an isotopically highly enriched 156Gd target. The data yield first direct support for the deformation dependence of effective proton and neutron quadrupole boson charges in the framework of algebraic nuclear models. First evidence for a low-lying Jπ=2+ member of the rotational band of states on top of the 1+ band head is obtained, too, indicating a significant signature splitting in the K =1 scissors mode rotational band.

  20. M1-E2 mixing ratios and B(E2) values for transitions in 131Xe

    International Nuclear Information System (INIS)

    Vijay Sai, K.; Deepa, S.; Ashish, T.; Venkataramaniah, K.; Madhusudan, K.

    2012-01-01

    The accuracies of M1-E2 mixing ratios calculated from the experimental conversion coefficients α i depend upon the accuracy with which the conversion coefficients are determined and also on the accuracy of the theoretical values. Recently a new calculation of ICCs by Band et al, BRICC has been published. The calculations are based on the relativistic DF method in which the exchange interactions between bound electrons and free electrons receding to infinity during the conversion process are treated exactly. Gerl et al showed that BRICC values are more closer to experimental values when compared to earlier theoretical values of Hager and Seltzer and Rosel. The availability of the BRICC values is expected to increase the accuracy with which the estimated quadrupole contents can be obtained

  1. Temperature-dose relationships with aflatoxin M1 in milk on the brine shrimp (Artemia salina larvae

    Directory of Open Access Journals (Sweden)

    Lejla Duraković

    2011-06-01

    Full Text Available Temperature-dose relationships with aflatoxin M1 (AFM1 were studied using the brine shrimp Artemia salina larvae as an biological indicator in the temperature range from 20 °C to 40 °C. Increase in the incubation temperature resulted in sensitivity increase by the brine shrimp to AFM1. Optimum sensitivity occured at 30 °C. Positive results were obtained at 0.18 μg AFM1 x L-1 of whole pasteurized milk with a mortality of over 15%. Greater than 90 % mortality occurred at dose levels of 0.9 μg AFM1 x L-1 and above. The test can be conducted during 30-60 hours.

  2. Performance of an M/M/1 Retrial Queue with Working Vacation Interruption and Classical Retrial Policy

    Directory of Open Access Journals (Sweden)

    Tao Li

    2016-01-01

    Full Text Available An M/M/1 retrial queue with working vacation interruption is considered. Upon the arrival of a customer, if the server is busy, it would join the orbit of infinite size. The customers in the orbit will try for service one by one when the server is idle under the classical retrial policy with retrial rate nα, where n is the size of the orbit. During a working vacation period, if there are customers in the system at a service completion instant, the vacation will be interrupted. Under the stable condition, the probability generating functions of the number of customers in the orbit are obtained. Various system performance measures are also developed. Finally, some numerical examples and cost optimization analysis are presented.

  3. E2 decay strength of the M1 scissors mode of ^{156}Gd and its first excited rotational state.

    Science.gov (United States)

    Beck, T; Beller, J; Pietralla, N; Bhike, M; Birkhan, J; Derya, V; Gayer, U; Hennig, A; Isaak, J; Löher, B; Ponomarev, V Yu; Richter, A; Romig, C; Savran, D; Scheck, M; Tornow, W; Werner, V; Zilges, A; Zweidinger, M

    2017-05-26

    The E2/M1 multipole mixing ratio δ_{1→2} of the 1_{sc}^{+}→2_{1}^{+} γ-ray decay in ^{156}Gd and hence the isovector E2 transition rate of the scissors mode of a well-deformed rotational nucleus has been measured for the first time. It has been obtained from the angular distribution of an artificial quasimonochromatic linearly polarized γ-ray beam of energy 3.07(6) MeV scattered inelastically off an isotopically highly enriched ^{156}Gd target. The data yield first direct support for the deformation dependence of effective proton and neutron quadrupole boson charges in the framework of algebraic nuclear models. First evidence for a low-lying J^{π}=2^{+} member of the rotational band of states on top of the 1^{+} band head is obtained, too, indicating a significant signature splitting in the K=1 scissors mode rotational band.

  4. Pancreas of C57 black mice after long-term space flight (Bion-M1 Space Mission)

    Science.gov (United States)

    Proshchina, A. E.; Krivova, Y. S.; Saveliev, S. C.

    2015-11-01

    In this study, we analysed the pancreases of C57BL/6N mice in order to estimate the effects of long-term space flights. Mice were flown aboard the Bion-M1 biosatellite, or remained on ground in the control experiment that replicated environmental and housing conditions in the spacecraft. Vivarium control group was used to account for housing effects. Each of the groups included mice designated for recovery studies. Mice pancreases were dissected for histological and immunohistochemical examinations. Using a morphometry and statistical analysis, a strong correlation between the mean islet size and the mean body weight was revealed in all groups. Therefore, we propose that hypokinesia and an increase in nutrition play an important role in alterations of the endocrine pancreas, both in space flight and terrestrial conditions.

  5. Un apéndice ornamental a Reyes en el ms. M1 de la Universidad Complutense de Madrid

    Directory of Open Access Journals (Sweden)

    de Azcárraga, M. J.

    2004-12-01

    Full Text Available The analysis of the ornamental masorah of folio 158a of Manuscript M1 allows the author to correct and improve the description made by Ch. D. Ginsburg in his introduction to the Bible. The author indeed agrees on the identification of the text as a masoretic appendix to the books of Kings. However, the beginning and the contents of the manuscript must be revised. Ginsburg describes only one of the four lists of the appendix, namely the one dealing with the differences between Eastern and Western recensions; the other three lists are the following: sedarim, peseqim, and words vocalized with patah, which are exceptional because they are pausal forms.

    El estudio detallado de la masora ornamental del folio 158a del manuscrito M1 me ha permitido corregir y puntualizar la descripción que hace de este folio Ch. D. Ginsburg en la Introducción a su Biblia. Por una parte, estamos de acuerdo en que se trata de un apéndice masorético a los libros de Reyes, pero no lo estamos en lo que se refiere al sitio donde comienza, ni al contenido total del mismo. Ginsburg sólo describe una lista de las cuatro que contiene, la de las diferencias entre los textos orientales y occidentales; las otras tres son: sedarîm, paseqîm y palabras vocalizadas con patah, que constituyen una excepción por estar en pausa.

  6. Accumulation of M1-like macrophages in type 2 diabetic islets is followed by a systemic shift in macrophage polarization.

    Science.gov (United States)

    Cucak, Helena; Grunnet, Lars Groth; Rosendahl, Alexander

    2014-01-01

    Human T2D is characterized by a low-grade systemic inflammation, loss of β-cells, and diminished insulin production. Local islet immunity is still poorly understood, and hence, we evaluated macrophage subpopulations in pancreatic islets in the well-established murine model of T2D, the db/db mouse. Already at 8 weeks of disease, on average, 12 macrophages were observed in the diabetic islets, whereas only two were recorded in the nondiabetic littermates. On a detailed level, the islet resident macrophages increased fourfold compared with nondiabetic littermates, whereas a pronounced recruitment (eightfold) of a novel subset of macrophages (CD68+F4/80-) was observed. The majority of the CD68+F4/80+ but only 40% of the CD68+F4/80- islet macrophages expressed CD11b. Both islet-derived macrophage subsets expressed moderate MHC-II, high galectin-3, and low CD80/CD86 levels, suggesting the cells to be macrophages rather than DCs. On a functional level, the vast majority of the macrophages in the diabetic islets was of the proinflammatory, M1-like phenotype. The systemic immunity in diabetic animals was characterized by a low-grade inflammation with elevated cytokine levels and increase of splenic cytokine, producing CD68+F4/80- macrophages. In late-stage diabetes, the cytokine signature changed toward a TGF-β-dominated profile, coinciding with a significant increase of galectin-3-positive macrophages in the spleen. In summary, our results show that proinflammatory M1-like galectin-3+ CD80/CD86(low) macrophages invade diabetic islets. Moreover, the innate immunity matures in a diabetes-dependent manner from an initial proinflammatory toward a profibrotic phenotype, supporting the concept that T2D is an inflammatory disease.

  7. Concurrent chemoradiotherapy for T4 and/or M1 LYM squamous cell carcinoma of the esophagus

    Energy Technology Data Exchange (ETDEWEB)

    Miyata, Yoshinori; Seki, Shigeki [Saku Central Hospital, Usuda, Nagano (Japan); Ohtsu, Atsushi; Kaneko, Kazuhiro; Nakamura, Akira

    2000-07-01

    A phase II study was conducted to investigate the efficacy and feasibility of chemoradiotherapy for locally advanced carcinoma of the esophagus. Fifty-four patients with clinical T4 and/or M1 LYM squamous cell carcinoma of the esophagus were enrolled. Patients received protracted infusions of fluorouracil 400 mg/m{sup 2}/24 hours on days 1 to 5 and 8 to 12, 2-hour infusions of cisplatin 40 mg/m{sup 2} on days 1 and 8, and concurrent radiotherapy at a dose of 30 Gy in 15 fractions over 3 weeks. Filgrastim was prophylactically administered to 35 patients. This schedule was repeated twice every 5 weeks, for a total radiation dose of 60 Gy followed by two courses of fluorouracil (800 mg/m{sup 2}/24 hours for 5 days) and cisplatin (80 mg/m{sup 2} on day 1). There were 36 patients with T4 disease and 33 with M1 LYM. Forty-nine patients (91%) completed the chemoradiotherapy segment. The 18 patients (33%) who achieved a complete response included nine (25%) of the 36 with T4 disease and nine (50%) of the 18 with non-T4 disease. Major toxicities were leukopenia and esophagitis; there were four (7%) treatment-related deaths. Prophylactic filgrastim reduced the incidence of grade 3 or worse leukopenia without improving dose-intensity or response. With a median follow-up duration of 43 months, median survival time was 9 months. The 3-year survival rate was 23%. Despite its significant toxicity, this combined modality seemed to have curative potential even in cases of locally advanced carcinoma of the esophagus. (author)

  8. 42 CFR 137.410 - For the purposes of section 110 of the Act [25 U.S.C. 450m-1] does the term contract include...

    Science.gov (United States)

    2010-10-01

    ....C. 450m-1] does the term contract include compacts, funding agreements, and construction project... the term contract include compacts, funding agreements, and construction project agreements entered into under Title V? Yes, for the purposes of section 110 of the Act [25 U.S.C. 450m-1] the term...

  9. ABCG2-overexpressing S1-M1-80 cell xenografts in nude mice keep original biochemistry and cell biological properties.

    Science.gov (United States)

    Wang, Fang; Liang, Yong-Ju; Wu, Xing-Ping; Su, Xiao-Dong; Fu, Li-Wu

    2012-03-01

    S1-M1-80 cells, derived from human colon carcinoma S1 cells, are mitoxantrone-selected ABCG2-overexpressing cells and are widely used in in vitro studies of multidrug resistance(MDR). In this study, S1-M1-80 cell xenografts were established to investigate whether the MDR phenotype and cell biological properties were maintained in vivo. Our results showed that the proliferation, cell cycle, and ABCG2 expression level in S1-M1-80 cells were similar to those in cells isolated from S1-M1-80 cell xenografts (named xS1-M1-80 cells). Consistently, xS1-M1-80 cells exhibited high levels of resistance to ABCG2 substrates such as mitoxantrone and topotecan, but remained sensitive to the non-ABCG2 substrate cisplatin. Furthermore, the specific ABCG2 inhibitor Ko143 potently sensitized xS1-M1-80 cells to mitoxantrone and topotecan. These results suggest that S1-M1-80 cell xenografts in nude mice retain their original cytological characteristics at 9 weeks. Thus, this model could serve as a good system for further investigation of ABCG2-mediated MDR.

  10. Limited similarity between plasmids encoding CTX-M-1 β-lactamase in Escherichia coli from humans, pigs, cattle, organic poultry layers and horses in Denmark

    DEFF Research Database (Denmark)

    Jakobsen, Lotte; Bortolaia, Valeria; Bielak, Eliza Maria

    2015-01-01

    in Denmark between 2006 and 2010. In total, 65 CTX-M-1-producing isolates from patients (n=22), pigs (n=21), cattle (n=4), organic poultry layers (n=3) and horses (n=15) were typed by pulsed-field gel electrophoresis (PFGE). Plasmids harbouring blaCTX-M-1 were characterised by S1 PFGE, PCR-based replicon...

  11. Genetics analysis of mutagenic effect on M1 and M2 of arabidopsis thaliana derived from the seeds implanted by low energy ion

    International Nuclear Information System (INIS)

    Chen Donghua; Liang Qianjin; Zhang Genfa; Zhang Wenjun; Zhang Xiangqi

    2001-01-01

    Ameliorated RAPD technique was used to analyze the variations and their genetic stability of the gene pool DNAs of M 1 generation of different ion implanted (into seeds) Arabidopsis thaliana and the individual plant DNAs of generations M 1 and M 2 . The analysis of the gene pool DNAs of generation M 1 suggested that: 53 of 178 random primers amplified differential fragments, and multiplication experiments testified that the PCR results of some primers showed considerable stability. The results revealed that variation percentages, within a certain limit, relates to implanting dosage. Particularly, the genetic stability analysis of generation M 2 certificates that: performing PCR analysis by means of the same primers of generation M 1 brought about variation bands identical with that of generation M 1 , so it is possible that variations induced by ion implanting may be truly hereditary

  12. Ischemic Stroke Due to Middle Cerebral Artery M1 Segment Occlusion: Latvian Stroke Register Data / Išēmisks Insults Sakarā ar Arteria Cerebri Media M1 Segmenta Oklūziju: Insulta Reģistra Dati

    Directory of Open Access Journals (Sweden)

    Valante Ramona

    2015-09-01

    Full Text Available Išēmisks insults visbiežāk notiek vidējās cerebrālās artērijas apasiņošanas baseinā. Tika veikts retrospektīvs Insulta reģistra datu pētījums. Pētījumam tika atlasīti un apstrādāti pacientu dati laika periodā no 2013. gada janvāra līdz 2014. decembrim. Datu analīzei tika atlasīti 478 pacienti, kuriem ar angiogrāfijas metodi, bija apstiprināta ACM oklūzija. Puse no pacientiem bija vīrieši 237 (49,6% ar vidējo vecumu 69,51 gadi, sievietēm vidējais vecums bija 74,58 gadi. Biežākais insulta cēlonis bija kardioembolija - 294 (61, 5% gadījumos. Sīko asinsvadu saslimšana nebija kā cēlonis ACM M1 segmenta oklūzijas gadījumā. Reperfūzijas terapiju saņēma 209 (43,7% pacienti. Iestājoties neiroloģiskais stāvoklis abās grupās bija līdzīgs, taču izrakstoties lielāks uzlabojums bija reperfūzijas terapijas grupā NIHSS 6,82 salīdzinot ar konservatīvas terapijas grupu - NIHSS 8,2 (SD ± 6,23 (p < 0,05. Izrakstoties pacientu funkcionālais stāvoklis bija labāks reperfūzijas grupā, mRS 0-2 bija 39,2% gadījumu, kā arī slikts funkcionālais iznākums (mRS 4-5 bija sastopams retāk - tikai 34,5% gadījumu. Mirstība arī bija zemāka reperfūzijas grupā - 7,6%, salīdzinot ar konservatīvās terapijas grupu - 13,4%. Biežākais cēlonis ACM M1 segmenta oklūzijas insultam ir kardioembolija. Pacientiem ir liela atkārtotu insultu incidence. Iestājoties reperfūzijas terapijas un konservatīvas terapijas grupu pacientiem neiroloģiskais stāvoklis bija līdzīgs. Taču reperfūzijas grupā pacientiem izrakstoties bija ievērojamāks uzlabojums novērtējot neiroloģisko stāvokli. Arī funkcionālais stāvoklis izrakstoties bija labāks pacientiem, kas saņēma reperfūzijas terapiju.

  13. KBE009: An antimalarial bestatin-like inhibitor of the Plasmodium falciparum M1 aminopeptidase discovered in an Ugi multicomponent reaction-derived peptidomimetic library.

    Science.gov (United States)

    González-Bacerio, Jorge; Maluf, Sarah El Chamy; Méndez, Yanira; Pascual, Isel; Florent, Isabelle; Melo, Pollyana M S; Budu, Alexandre; Ferreira, Juliana C; Moreno, Ernesto; Carmona, Adriana K; Rivera, Daniel G; Alonso Del Rivero, Maday; Gazarini, Marcos L

    2017-09-01

    Malaria is a global human parasitic disease mainly caused by the protozoon Plasmodium falciparum. Increased parasite resistance to current drugs determines the relevance of finding new treatments against new targets. A novel target is the M1 alanyl-aminopeptidase from P. falciparum (PfA-M1), which is essential for parasite development in human erythrocytes and is inhibited by the pseudo-peptide bestatin. In this work, we used a combinatorial multicomponent approach to produce a library of peptidomimetics and screened it for the inhibition of recombinant PfA-M1 (rPfA-M1) and the in vitro growth of P. falciparum erythrocytic stages (3D7 and FcB1 strains). Dose-response studies with selected compounds allowed identifying the bestatin-based peptidomimetic KBE009 as a submicromolar rPfA-M1 inhibitor (K i =0.4μM) and an in vitro antimalarial compound as potent as bestatin (IC 50 =18μM; without promoting erythrocyte lysis). At therapeutic-relevant concentrations, KBE009 is selective for rPfA-M1 over porcine APN (a model of these enzymes from mammals), and is not cytotoxic against HUVEC cells. Docking simulations indicate that this compound binds PfA-M1 without Zn 2+ coordination, establishing mainly hydrophobic interactions and showing a remarkable shape complementarity with the active site of the enzyme. Moreover, KBE009 inhibits the M1-type aminopeptidase activity (Ala-7-amido-4-methylcoumarin substrate) in isolated live parasites with a potency similar to that of the antimalarial activity (IC 50 =82μM), strongly suggesting that the antimalarial effect is directly related to the inhibition of the endogenous PfA-M1. These results support the value of this multicomponent strategy to identify PfA-M1 inhibitors, and make KBE009 a promising hit for drug development against malaria. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Direct Observation of the M1 Transition between the Ground Term Fine Structure Levels of W VIII

    Directory of Open Access Journals (Sweden)

    Momoe Mita

    2017-03-01

    Full Text Available We present a direct observation of the M1 transition between the fine structure splitting in the 4 f 13 5 s 2 5 p 6 2 F ground term of W VIII. The spectroscopic data of few-times ionized tungsten ions are important for the future ITER diagnostics, but there is a serious lack of data. The present study is part of an ongoing effort to solve this problem. Emission from the tungsten ions produced and trapped in a compact electron beam ion trap is observed with a Czerny–Turner visible spectrometer. Spectra in the EUV range are also observed at the same time to help identify the previously-unreported visible lines. The observed wavelength 574.47 ± 0.03 nm (air, which corresponds to the fine structure splitting of 17,402.5 ± 0.9 cm − 1 , shows reasonable agreement with the previously reported value 17,410 ± 5 cm − 1 obtained indirectly through the analysis of EUV spectra [Ryabtsev et al., Atoms 3 (2015 273].

  15. Bidirectional multi-optical line terminals incorporated converged WSN-PON network using M/M/1 queuing

    Science.gov (United States)

    Kumar, Love; Sharma, Vishal; Singh, Amarpal

    2017-12-01

    Wireless Sensor Networks (WSNs) have an assortment of application areas, for instance, civil, military, and video surveillance with restricted power resources and transmission link. To accommodate the massive traffic load in hefty sensor networks is another key issue. Subsequently, there is a necessity to backhaul the sensed information of such networks and prolong the transmission link to access the distinct receivers. Passive Optical Network (PON), a next-generation access technology, comes out as a suitable candidate for the convergence of the sensed data to the core system. The earlier demonstrated work with single-OLT-PON introduces an overloaded buffer akin to video surveillance scenarios. In this paper, to combine the bandwidth potential of PONs with the mobility capability of WSNs, the viability for the convergence of PONs and WSNs incorporating multi-optical line terminals is demonstrated to handle the overloaded OLTs. The existing M/M/1 queue theory with interleaving polling with adaptive cycle time as dynamic bandwidth algorithm is used to shun the probability of packets clash. Further, the proposed multi-sink WSN and multi-OLT PON converged structure is investigated in bidirectional mode analytically and through computer simulations. The observations establish the proposed structure competent to accommodate the colossal data traffic through less time consumption.

  16. Status of prompt gamma neutron activation analysis (PGAA) at TRR-1/M1 (Thai Research Reactor-1/Modified 1)

    Energy Technology Data Exchange (ETDEWEB)

    Asvavijnijkulchai, Chanchai; Dharmavanij, Wanchai; Siangsanan, Pariwat; Ratanathongchai, Wichian; Chongkum, Somporn [Physics Division, Office of Atomic Energy for Peace, Vibhavadi Rangsit Road, Chatuchak, Bangkok (Thailand)

    1999-08-01

    The first prompt gamma activation analysis (PGAA) was designed, constructed and installed at a 6 inch diameter neutron beam port of the Thai Research Reactor-1/Modified 1 (TRR-1/M1) since 1989. Beam characteristic were made by Gd foil irradiation, X-ray film exposing and densitometry scanning consequently. The thermal neutron flux at sample position was measured by Au foil activation, and was about 1 x 10{sup 7} n.cm{sup 2}.sec{sup -1} at 700 kW operating power. The experiments have been conducted successfully. In 1998, the PGAA facility has been developed for the reactor operating power at 1.2 MW. The new PGAA system, e.g., beam shutter, gamma collimator and biological shields have been designed to reduce the leakage of neutrons and gamma radiation to the acceptance levels in accordance with the International Commission on Radiation Protection Publication 60 (ICRP 60). The construction and installation will be completed in April 1999. (author)

  17. Effects of a Finger Tapping Fatiguing Task on M1-Intracortical Inhibition and Central Drive to the Muscle.

    Science.gov (United States)

    Madrid, Antonio; Madinabeitia-Mancebo, Elena; Cudeiro, Javier; Arias, Pablo

    2018-06-19

    The central drive to the muscle reduces when muscle force wanes during sustained MVC, and this is generally considered the neurophysiological footprint of central fatigue. The question is if force loss and the failure of central drive to the muscle are responsible mechanisms of fatigue induced by un-resisted repetitive movements. In various experimental blocks, we validated a 3D-printed hand-fixation system permitting the execution of finger-tapping and maximal voluntary contractions (MVC). Subsequently, we checked the suitability of the system to test the level of central drive to the muscle and developed an algorithm to test it at the MVC force plateau. Our main results show that the maximum rate of finger-tapping dropped at 30 s, while the excitability of inhibitory M1-intracortical circuits and corticospinal excitability increased (all by approximately 15%). Furthermore, values obtained immediately after finger-tapping showed that MVC force and the level of central drive to the muscle remained unchanged. Our data suggest that force and central drive to the muscle are not determinants of fatigue induced by short-lasting un-resisted repetitive finger movements, even in the presence of increased inhibition of the motor cortex. According to literature, this profile might be different in longer-lasting, more complex and/or resisted repetitive movements.

  18. Effects of carbon ion irradiation on survival rate, catalase and peroxidase activity of alfalfa M1 under low temperature stress

    International Nuclear Information System (INIS)

    Wang Shuyang; Li Jinghua; Jiang Boling

    2014-01-01

    In this study, three kinds of alfalfa including Zhonglan 1, BC-04-477 and Ta Cheng were treated with different doses of "1"2C"6"+ (75 keV) heavy ion radiation, and then the influence of survival rate, catalase (CAT) and peroxidase (POD) activity of M1 with low temperature stress were tested. The results showed that under the condition of 400 Gy radiation dose, the survival rate and CAT activity of Zhonglan 1 under low temperature stress have increased by 33.3%, 56.3% respectively compared with those of the control group, while there was no difference in POD activity between those two groups. The survival rate, CAT and POD activity of BC-04-477 treated with low temperature have been improved by 33.3%, 69.2%, 5.1% respectively compared with those of the control group when the radiation dose was 400 Gy. Compared with those of the control group, the survival rate, CAT and POD activity of Ta Cheng under low temperature stress have been improved by 25%, 26%,22.8% respectively when the radiation dose was 800 Gy. These results indicate that the viability and the cold resistance ability of Zhong Lan 1, BC-04-477 and Ta Cheng can be improved by "1"2C"6"+ radiation. (authors)

  19. DNase Sda1 allows invasive M1T1 Group A Streptococcus to prevent TLR9-dependent recognition.

    Directory of Open Access Journals (Sweden)

    Satoshi Uchiyama

    Full Text Available Group A Streptococcus (GAS has developed a broad arsenal of virulence factors that serve to circumvent host defense mechanisms. The virulence factor DNase Sda1 of the hyperinvasive M1T1 GAS clone degrades DNA-based neutrophil extracellular traps allowing GAS to escape extracellular killing. TLR9 is activated by unmethylated CpG-rich bacterial DNA and enhances innate immune resistance. We hypothesized that Sda1 degradation of bacterial DNA could alter TLR9-mediated recognition of GAS by host innate immune cells. We tested this hypothesis using a dual approach: loss and gain of function of DNase in isogenic GAS strains and presence and absence of TLR9 in the host. Either DNA degradation by Sda1 or host deficiency of TLR9 prevented GAS induced IFN-α and TNF-α secretion from murine macrophages and contributed to bacterial survival. Similarly, in a murine necrotizing fasciitis model, IFN-α and TNF-α levels were significantly decreased in wild type mice infected with GAS expressing Sda1, whereas no such Sda1-dependent effect was seen in a TLR9-deficient background. Thus GAS Sda1 suppressed both the TLR9-mediated innate immune response and macrophage bactericidal activity. Our results demonstrate a novel mechanism of bacterial innate immune evasion based on autodegradation of CpG-rich DNA by a bacterial DNase.

  20. Comparisons of sensitivity on X-ray and diethyl sulfate in M1 seedling stage of welsh onion

    International Nuclear Information System (INIS)

    Lee, B.K.; Eun, J.S.; Park, H.B.

    1977-01-01

    In order to select useful mutants, dormant seeds of a Welsh onion variety ''Baekeunju'' were treated with different levels of X-ray and diethyl sulfate (DES). For this study, the sensitivities on germination, emergence, seedling height, and chromosome aberrations in root tip cells were investigated in M 1 seedling stage. The results obtained were summarized as follow: The germination rate was not influenced by X-ray irradiation but in plots of DES treatment it was significantly decreased according to increasing of the DES concentration. A significant reduction to emergence rate and seedling height measured on 30th day after sowing was in direct proportion to increasing of the X-ray dose and the DES concentration. Fifty per cent growth reduction dose and concentration was determined to about 33kR for X-ray, and about 0.12% for EES. The chromosome aberration, such as chromosome fragment, chromosome bridge and chromosomering, was shown much frequently in plants treated with high dose or concentration of the both mutagens. However, the DES made less aberration of chromosome than the X-ray in average of all the treated concentrations. A trend was also observed that the X-ray irradiation made more chromosome fragments than chromosome bridges and the DES treatment more chromosome bridges than chromosome fragments. (author)

  1. Occurrence of aflatoxin M(1) in some samples of UHT, raw & pasteurized milk from Indian states of Karnataka and Tamilnadu.

    Science.gov (United States)

    Siddappa, Vinutha; Nanjegowda, Divyashree Kallenahalli; Viswanath, Prema

    2012-11-01

    Aflatoxin M(1) (AFM(1)) is a toxic metabolite found in the milk of lactating animals which have consumed feedstuffs contaminated with aflatoxin B(1). Ultra high temperature treated (UHT) milk is a product which is becoming popular in developing countries like India as there is a lack of proper cold storage or refrigeration facilities. In this study, 45 samples of UHT milk of popular brands prevalent in the market were analyzed for the presence of AFM(1) by reversed phase HPLC using fluorescent detector after cleanup of sample with immunoaffinity columns. All samples of plain UHT milk were positive for AFM(1) and 38% of these contained levels more than 0.5 μg/kg, the maximum permitted limit prescribed by the Codex Alimentarius Commission and by the mandatory regulations of the country, the FSSAI Regulations, 2011. In 62.5% of flavored UHT milk, AFM(1) was below detectable levels (0.02 μgL(-1)). However, 12.5% of these samples also contained levels exceeding the maximum permitted limits. AFM(1) was present in 61.6% of the 52 raw milk samples analyzed from the two states of Karnataka and Tamilnadu with a range of 0.1-3.8 μgL(-1). 17.3% of these samples also exceeded the regulatory limits of the country. Copyright © 2012 Elsevier Ltd. All rights reserved.

  2. Column Number Density Expressions Through M = 0 and M = 1 Point Source Plumes Along Any Straight Path

    Science.gov (United States)

    Woronowicz, Michael

    2016-01-01

    Analytical expressions for column number density (CND) are developed for optical line of sight paths through a variety of steady free molecule point source models including directionally-constrained effusion (Mach number M = 0) and flow from a sonic orifice (M = 1). Sonic orifice solutions are approximate, developed using a fair simulacrum fitted to the free molecule solution. Expressions are also developed for a spherically-symmetric thermal expansion (M = 0). CND solutions are found for the most general paths relative to these sources and briefly explored. It is determined that the maximum CND from a distant location through directed effusion and sonic orifice cases occurs along the path parallel to the source plane that intersects the plume axis. For the effusive case this value is exactly twice the CND found along the ray originating from that point of intersection and extending to infinity along the plume's axis. For sonic plumes this ratio is reduced to about 4/3. For high Mach number cases the maximum CND will be found along the axial centerline path. Keywords: column number density, plume flows, outgassing, free molecule flow.

  3. Schiff base: A high affinity chemical agent to decrease the concentration of aflatoxin M1 in raw milk contaminated artificially

    Directory of Open Access Journals (Sweden)

    Frane Delaš

    2012-03-01

    Full Text Available In the present study were conducted the effect of pH (5.5, 6.0 and 6.5 and concentration of new synthesized 3-/2-aminophenylimino-(p-toluoyl/-4-hydroxy-6-(p-tolyl-2H-pyrane-2-one (Schiff base on decrease the concentration of aflatoxin M1 (AFM1 in raw milk contaminated with known concentration of this toxin. Experiments were carried out at temperature of 4 °C during 35 days. At pH 5.5 Schiff base concentration of 0.1 µmol/L was lessening the concentration of AFM1 after 35 days by 55 %. However, at pH 6.5 the most effective concentration for lessening of AFM1 was 0.5 µmol/L. Schiff base was not effective at pH value of 7 or higher. The ability of Schiff base to act as antimycotoxigenic agent provides new perspective for possibly using this compound to control AFM1 contamination in milk and to extent shelf lives of this food. Detection of toxicity of investigated Schiff base was performed by using the brine shrimp (Artemia salina larvae as an biological indicator to determine their sensitivity to this chemical agent.

  4. Computational modeling with fluid-structure interaction of the severe m1 stenosis before and after stenting.

    Science.gov (United States)

    Park, Soonchan; Lee, Sang-Wook; Lim, Ok Kyun; Min, Inki; Nguyen, Minhtuan; Ko, Young Bae; Yoon, Kyunghwan; Suh, Dae Chul

    2013-02-01

    Image-based computational models with fluid-structure interaction (FSI) can be used to perform plaque mechanical analysis in intracranial artery stenosis. We described a process in FSI study applied to symptomatic severe intracranial (M1) stenosis before and after stenting. Reconstructed 3D angiography in STL format was transferred to Magics for smoothing of vessel surface and trimming of branch vessels and to HyperMesh for generating tetra volume mesh from triangular surface-meshed 3D angiogram. Computational analysis of blood flow in the blood vessels was performed using the commercial finite element software ADINA Ver 8.5. The distribution of wall shear stress (WSS), peak velocity and pressure was analyzed before and after intracranial stenting. The wall shear stress distributions from Computational fluid dynamics (CFD) simulation with rigid wall assumption as well as FSI simulation before and after stenting could be compared. The difference of WSS between rigid wall and compliant wall model both in pre- and post-stent case is only minor except at the stenosis region. These WSS values were greatly reduced after stenting to 15~20 Pa at systole and 3~5 Pa at end-diastole in CFD simulation, which are similar in FSI simulations. Our study revealed that FSI simulation before and after intracranial stenting was feasible despite of limited vessel wall dimension and could reveal change of WSS as well as flow velocity and wall pressure.

  5. Agomelatine or ramelteon as treatment adjuncts in glioblastoma and other M1- or M2-expressing cancers.

    Science.gov (United States)

    Kast, Richard E

    2015-01-01

    The impressive but sad list of over forty clinical studies using various cytotoxic chemotherapies published in the last few years has failed to increase median survival of glioblastoma beyond two years after diagnosis. In view of this apparent brick wall, adjunctive non-cytotoxic growth factor blocking drugs are being tried, as in the CUSP9* protocol. A related theme is searching for agonists at growth inhibiting receptors. One such dataset is that of melatonin agonism at M1 or M2 receptors found on glioblastoma cells, being a negative regulator of these cells' growth. Melatonin itself is an endogenous hormone, but when used as an exogenously administered drug it has many disadvantages. Agomelatine, marketed as an antidepressant, and ramelteon, marketed as a treatment for insomnia, are currently-available melatonin receptor agonists. These melatonin receptor agonists have significant advantages over the natural ligand: longer half-life, better oral absorption, and higher affinity to melatonin receptors. They have an eminently benign side effect profile. As full agonists they should function to inhibit glioblastoma growth, as demonstrated for melatonin. A potentially helpful ancillary attribute of melatonergic agonists in glioblastoma treatment is an increase in interleukin-2 synthesis, expected, at least partially, to reverse some of the immunosuppression associated with glioblastoma.

  6. Results of VVER fuel rods tests in the MIR.M1 reactor under power cycling conditions

    International Nuclear Information System (INIS)

    Burukin, A.; Izhutov, A.; Ovchinnikov, V.; Kalygin, V.; Markov, D.; Pimenov, Y.; Novikov, V.; Medvedev, A.; Nesterov, B.

    2011-01-01

    The paper presents the main results of the 50 ... 60 MWd/kgU burnup VVER fuel rods tests performed in the MIR.M1 reactor loop facilities under power cycling. The non-destructive PIE results are presented as well. A series of experiments was performed, including overall measurement of fuel rod parameters test, in one of which 300 cycles were done. Irradiation under power cycling conditions and PIE of high-burnup VVER fuel rods showed the following: 1) all fuel rods claddings preserved their integrity under irradiation at linear heat rate (LHR) higher than the NPP operating one; 2) experimental data were obtained on the axial and radial cladding strain and fission gas release (FGR) from 50 ... 60 MWd/kgU burnup VVER-440 and VVER-1000 fuel rods as well as on the kinetics of the change in these parameters and fuel temperature under the power cycling; 3) non-destructive PIE results are in a satisfactory correlation with the data obtained by means of in-pile measurement gages during irradiation. (authors)

  7. Description of strong M1 transitions between 4^+ states at N=52 within the sdg-IBM-2

    Science.gov (United States)

    Casperson, R. J.; Werner, V.; Heinze, S.

    2009-10-01

    The interplay between collective and single-particle degrees of freedom for nuclei near the N=50 shell closure have recently been under investigation. In Molybdenum and Ruthenium nuclei, collective symmetric and mixed-symmetric structures have been identified, while in Zirconium, underlying shell-structure plays an enhanced role. The one-phonon 2^+ mixed-symmetry state was identified from its strong M1 transition to the 2^+1 state. Similar transitions were observed between 4^+ states in ^94Mo and ^92Zr, and shell model calculations indicate that hexadecapole excitations play a role. These phenomena will be investigated within the sdg-Interacting Boson Model-2 in order to gain a better understanding about the structure of the states involved, and to which extent the hexadecapole degree of freedom is important at relatively low energies. First calculations within this model, using an F-spin conserving Hamiltonian to disentangle symmetric and mixed- symmetric structures, will be presented and compared to data.

  8. Obesity Contributes to Ovarian Cancer Metastatic Success Through Increased Lipogenesis, Enhanced Vascularity, and Decreased Infiltration of M1 Macrophages

    Science.gov (United States)

    Liu, Yueying; Metzinger, Matthew N.; Lewellen, Kyle A.; Cripps, Stephanie N.; Carey, Kyle D.; Harper, Elizabeth I.; Shi, Zonggao; Tarwater, Laura; Grisoli, Annie; Lee, Eric; Slusarz, Ania; Yang, Jing; Loughran, Elizabeth A.; Conley, Kaitlyn; Johnson, Jeff J.; Klymenko, Yuliya; Bruney, Lana; Liang, Zhong; Dovichi, Norman J.; Cheatham, Bentley; Leevy, W. Matthew; Stack, M. Sharon

    2015-01-01

    Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancy, with high mortality attributable to widespread intra-peritoneal (i.p.) metastases. Recent meta-analyses report an association between obesity, ovarian cancer incidence, and ovarian cancer survival, but the effect of obesity on metastasis has not been evaluated. The objective of this study was to use an integrative approach combining in vitro, ex vivo, and in vivo studies to test the hypothesis that obesity contributes to ovarian cancer metastatic success. Initial in vitro studies using three-dimensional meso-mimetic cultures showed enhanced cell-cell adhesion to the lipid-loaded mesothelium. Furthermore, in an ex vivo colonization assay, ovarian cancer cells exhibited increased adhesion to mesothelial explants excised from mice modeling diet-induced obesity (DIO), in which they were fed a "Western" diet. Examination of mesothelial ultrastructure revealed a substantial increase in the density of microvilli in DIO mice. Moreover, enhanced i.p. tumor burden was observed in overweight or obese animals in three distinct in vivo models. Further histological analyses suggested that alterations in lipid regulatory factors, enhanced vascularity, and decreased M1/M2 macrophage ratios may account for the enhanced tumorigenicity. Together, these findings show that obesity potently impacts ovarian cancer metastatic success, which likely contributes to the negative correlation between obesity and ovarian cancer survival. PMID:26573796

  9. Pipes out of the chromium-molybdenum 12Kh2M1 steel intended for power units

    International Nuclear Information System (INIS)

    Saf'yanov, A.V.; Plyatskovskij, O.A.; Khokhlov-Nekrasov, O.G.; Palatnikova, E.S.; Karpenko, N.P.

    1977-01-01

    Vanadiumless steel 12Kh2M1 (2.25%Cr, 1%Mo) known to be applied abroad has been used for production of 325x60 mm tubes. The technology involves heating of the blanks to 1270-1300 deg C, their piercing in a double-roller mill, rolling on a pilger mill 8-16'' in thick wall caliber rolls, thermal treatment (normalizing at 930-960 deg C for 1 hour and tempering at 730+-10 deg C for 4 hours and etching (12-22% H 2 SO 4 and up to 143 g/l FeSO 4 ) for 3-4 hours at 55-65 deg C. Good technological properties of the steel and its capacity of working at 540-580 deg C are confirmed. Vanadium alloying of boiler steels does not provide for essential improvement of oxydation resistance and long term strength, but decreases the workability and enhances scatter of working parameters on account of minor variations of chemical composition

  10. Tokamak m = 1 magnetohydrodynamic calculations in toroidal geometry using a full set of nonlinear resistive magnetohydrodynamic equations

    International Nuclear Information System (INIS)

    Charlton, L.A.; Carreras, B.A.; Holmes, J.A.; Lynch, V.E.

    1988-01-01

    The linear stability and nonlinear evolution of the resistive m = 1 mode in tokamaks is studied using a full set of resistive magnetohydrodynamic (MHD) equations in toroidal geometry. The modification of the linear and nonlinear properties of the mode by a combination of strong toroidal effects and low resistivity is the focus of this work. Linearly there is a transition from resistive kink to resistive tearing behavior as the aspect ratio and resistivity are reduced, and there is a corresponding modification of the nonlinear behavior, including a slowing of the island growth and development of a Rutherford regime, as the tearing regime is approached. In order to study the sensitivity of the stability and evolution to assumptions concerning the equation of state, two sets of full nonlinear resistive MHD equations (a pressure convection set and an incompressible set) are used. Both sets give more stable nonlinear behavior as the aspect ratio is reduced. The pressure convection set shows a transition from a Kadomtsev reconnection at large aspect ratio to a saturation at small aspect ratio. The incompressible set yields Kadomtsev reconnection for all aspect ratios, but with a significant lengthening of the reconnection time and development of a Rutherford regime at an aspect ratio approaching the transition from a resistive kink mode to a tearing mode. The pressure convection set gives an incomplete reconnection similar to that sometimes seen experimentally. The pressure convection set is, however, strictly justified only at high beta

  11. Resin Infusion Fabrication of nanostructured PMC, Phase I

    Data.gov (United States)

    National Aeronautics and Space Administration — Polymer reinforced composite parts required for heavy lift launch vehicles are currently fabricated by hand lay-up or automated tape lay-up followed by curing using...

  12. Effect of 30-day orbital flight BION M1 on excretion of expired endogenous CO in mice

    Science.gov (United States)

    Shulagin, Yury; Tatarkin, Sergey; Dyachenko, Alexander

    It is known that increased destruction of hem structures is accompanied by increase of the endogenous carbon monoxide excretion rate with respiration (VCO). Changes VCO preceded the observed changes in the blood composition [D’yachenko A. et al., 2010]. Changes in blood composition, i.e. rise of red blood cells content and reduction of reticulocytes content was detected after a 12-day orbital flight (OF) in mice C57BL/6 [Gridley D.et al., 2003]. The purpose of this study was to investigate the effect of 30-day OF on excretion of endogenous CO. The method and apparatus for simultaneous measurement of VCO, and O2 and CO2 exchange were developed. The research consisted of three parts: 1). Measurement of VCO in five C57BL/6 mice after 30-day OF on the Russian satellite BION M1. 2). Measurement of VCO in six C57BL/6 mice after 30-day ground-based experiment (GBE) with simulated flight telemetry environment of BION M1. 3). Measurement of VCO in seven C57BL/6 mice in vivarium The results: Mice weight after OF was 24.3+-3.3 (mean +-SD) with minimal weight 18.1 g, and maximal weight 29.9 g. Vivarium mice weight was 27.0+-1.8 g. KGE mice weight was 25.0+-1.3 g. Mice age in all three groups was the same. We measured and estimated VCO and total CO excretion (MCO) for two gas mixtures ventilated mouse camera: atmospheric CO-contained air and then CO-free air(30 min). The results showed that the average MCO allocated GBE and vivarium mice did not significantly differ. Average MCO in mice after OF was significantly higher then in vivarium group (T=-2,74; p=0.02). MCO after GBE was between the vivarium and OF groups. MCO in OF and KGE groups did not differ ( T=-1,93; p=0,085). Blood tests in mice after OF was not carried out, because the recovery after the OF was studied in this group. The largest excretion of CO was observed in a mouse N39 after the OF. The weight of this mouse was only 18.1 g, i.e. much less than mean weight. Increase of VCO in food-restricted animal is known

  13. Effects of Lactobacillus kefiranofaciens M1 isolated from kefir grains on enterohemorrhagic Escherichia coli infection using mouse and intestinal cell models.

    Science.gov (United States)

    Chen, Y P; Lee, T Y; Hong, W S; Hsieh, H H; Chen, M J

    2013-01-01

    A potential probiotic strain, Lactobacillus kefiranofaciens M1, was previously isolated from kefir grains, which are used to manufacture the traditional fermented drink kefir. The aim of this study was to investigate the effects of Lb. kefiranofaciens M1 on enterohemorrhagic Escherichia coli (EHEC) infection, using mice and intestinal cell models. BALB/c mice were daily administrated with either phosphate buffered saline or Lb. kefiranofaciens M1 at 2×10(8) cfu/mouse per day intragastrically for 7 d. Intragastric challenges with EHEC (2×10(9) cfu/mouse) were conducted on d 0, 4, and 7 after treatment. Administration of Lb. kefiranofaciens M1 was able to prevent EHEC infection-induced symptoms, intestinal damage, renal damage, bacterial translocation, and Shiga toxin penetration. Furthermore, the mucosal EHEC-specific IgA responses were increased after Lb. kefiranofaciens M1 administration in the EHEC-infected mouse system. Additionally, in vitro, Lb. kefiranofaciens M1 was shown to have a protective effect on Caco-2 intestinal epithelial cells and Caco-2 intestinal epithelial cell monolayers; the bacteria limited EHEC-induced cell death and reduced the loss of epithelial integrity. These findings support the potential of Lb. kefiranofaciens M1 treatment as an approach to preventing EHEC infection and its effects. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  14. Mittelplate A23/A23M1. Geological and reservoir engineering concept of a dual-lateral well; Mittelplate A23/A23M1. Geologisches und lagerstaettentechnisches Konzept einer Duolateralbohrung

    Energy Technology Data Exchange (ETDEWEB)

    Osivandi, K.; Racher, D. [RWE Dea AG, Hamburg (Germany)

    2011-07-15

    The Mittelplate Oil Field is situated in the German Wadden Sea in the West Holstein Trough in the concession Heide/Buesum, about 100 km northwest of Hamburg. Operator is RWE Dea AG (50%), and the partner is Wintershall Holding GmbH (50%). Besides the reservoir layers of the Dogger Gamma, Delta, Epsilon, and Zeta, the shallow-marine/deltaic sandstone-shale-succession of the Dogger Beta (with its five oil-bearing sandstones of 1-5 m thickness each) forms the laterally widespread reservoir which was the target for Germany's and RWE Dea AG's first pressure-tight multilateral well. So far the Dogger-Beta-Reservoir has been developed with wells from the artificial island Mittelplate A using a 5-spot pattern with a successive concentric concept. In order to reduce the costs and effectively make use of the limited amount of slots, the development concept should be improved by implementing the multilateral technology. By targeting three drainage areas in total, the multilateral well Mittelplate A23/A23M1 was planned to produce oil at an initial rate of ca. 400 m{sup 3}/d. In order to achieve a horizontal interval of ca. 2640 m length, several LWD measurements including Gamma Ray- and Density- Images and Deep-Directional-Resistivity logs were necessary. The long horizontal exposure of the oil-bearing sandstone layers as well as the tangent sections for placement of the electrical submersible pump (ESP) and junction above the reservoir represented the main challenges during geological planning and realtime geosteering. A total perforation length of 1360 m was achieved, taking into account the required distances to neighboring producer wells and the laterally varying pore pressures. According to the latest production history of the well, a cumulative production of about 10% more than initially planned are expected after an initial production rate of 735 m{sup 3}/d. Thanks to the successful application of the multilateral technology and geosteering within the thin

  15. A review of the current situation of aflatoxin M1 in cow's milk in Serbia: risk assessment and regulatory aspects.

    Science.gov (United States)

    Milićević, Dragan R; Spirić, Danka; Radičević, Tatjana; Velebit, Branko; Stefanović, Srdjan; Milojević, Lazar; Janković, Saša

    2017-09-01

    The aim of this systematic review is to provide information regarding the incidence and levels of aflatoxin M 1 (AFM 1 ) in raw and heat processed cow's milk in Serbia during 2015-16 and to compare these with collected data on the occurrence of AFM 1 in raw milk and dairy products during the last decade in our region. Estimation of dietary exposure (EDI) and hazard index (HI) calculations for different age groups of the population were also carried out, based on the AFM 1 content of milk samples and on available food consumption data in Serbia. AFM 1 was detected in 69.9% (984/1408) of raw milk samples in 2015 versus 84.9% (3094/3646) in 2016, while in heat-processed milk, AFM 1 was detected in 77.8% (364/468) in 2015 versus 98.5% (753/765) in 2016. On the basis of the obtained results, 450 (9%) of raw and 14 (1.1%) of heat-processed milk samples were contaminated with AFM 1 levels above the maximum permitted level in Serbia (0.25 μg kg -1 ). However, a large percentage of raw and heat processed milk in Serbia (30.1% and 17.3%, respectively) was contaminated with AFM 1 levels above the maximum permitted level regulated in the European Union (0.05 μg kg -1 ). Therefore, in order to protect consumer health, it is extremely important to further control the level of aflatoxins in milk, and this should be considered as a high priority for risk management actions.

  16. Combined glutathione S transferase M1/T1 null genotypes is associated with type 2 diabetes mellitus

    Science.gov (United States)

    POROJAN, MIHAI D.; BALA, CORNELIA; ILIES, ROXANA; CATANA, ANDREEA; POPP, RADU A.; DUMITRASCU, DAN L.

    2015-01-01

    Background Due to new genetic insights, a considerably large number of genes and polymorphic gene variants are screened and linked with the complex pathogenesis of type 2 diabetes (DM). Our study aimed to investigate the association between the two isoforms of the glutathione S-transferase genes (Glutathione S transferase isoemzyme type M1- GSTM1 and Glutathione S transferase isoemzyme type T1-GSTT1) and the prevalence of DM in the Northern Romanian population. Methods We conducted a cross-sectional, randomized, case-control study evaluating the frequency of GSTM1 and GSTT1 null alleles in patients diagnosed with DM. A total of 106 patients diagnosed with DM and 124 healthy controls were included in the study. GSTM1 and GSTT1 null alleles genotyping was carried out using Multiplex PCR amplification of relevant gene fragments, followed by gel electrophoresis analysis of the resulting amplicons. Results Molecular analysis did not reveal an increased frequency of the null GSTM1 and GSTT1 alleles (mutant genotypes) respectively in the DM group compared to controls (p=0.171, OR=1.444 CI=0.852–2.447; p=0.647, OR=0.854, CI=0.436–1.673). Nevertheless, the combined GSTM1/GSTT1 null genotypes were statistically significantly higher in DM patients compared to control subjects (p=0.0021, OR=0.313, CI=0.149–0.655) Conclusions The main finding of our study is that the combined, double GSTM1/GSTT1 null genotypes are to be considered among the polymorphic genetic risk factors for type 2 DM. PMID:26528065

  17. A survey on Aflatoxin M1 content in sheep and goat milk produced in Sardinia Region, Italy (2005-2013

    Directory of Open Access Journals (Sweden)

    Salvatore Virdis

    2014-12-01

    Full Text Available In the present work the results of a survey conducted in Sardinia Region on Aflatoxin M1 (AFM1 contamination in milk of small ruminants from 2005 to 2013 are reported. A total of 517 sheep and 88 goat milk samples from bulk tank, tank trucks and silo tank milk were collected. Analyses were performed by the Regional Farmers Association laboratory using high-performance liquid chromatography following the ISO 14501:1998 standard. None of the sheep milk samples analysed during 2005- 2012 showed AFM1 contamination. In sheep milk samples collected in 2013, 8 out of 172 (4.6% were contaminated by AFM1 with a concentration (mean±SD of 12.59±14.05 ng/L. In one bulk tank milk sample 58.82 ng/L AFM1 was detected, exceeding the EU limit. In none of goat milk samples analysed from 2010 to 2012 AFM1 was detected. In 2013, 9 out of 66 goat milk samples (13.6% showed an AFM1 concentration of 47.21±19.58 ng/L. Two of these samples exceeded the EU limit, with concentrations of 62.09 and 138.6 ng/L. Higher contamination frequency and concentration rates were detected in bulk tank milk samples collected at farm than in bulk milk truck or silo samples, showing a dilution effect on AFM1 milk content along small ruminants supply chain. The rate and levels of AFM1 contamination in sheep and goat milk samples were lower than other countries. However, the small number of milk samples analysed for AFM1 in Sardinia Region in 2005-2013 give evidence that food business operators check programmes should be improved to ensure an adequate monitoring of AFM1 contamination in small ruminant dairy chain.

  18. Spaceflight on the Bion-M1 biosatellite alters cerebral artery vasomotor and mechanical properties in mice

    Science.gov (United States)

    Sofronova, Svetlana I.; Tarasova, Olga S.; Gaynullina, Dina; Borzykh, Anna A.; Behnke, Bradley J.; Stabley, John N.; McCullough, Danielle J.; Maraj, Joshua J.; Hanna, Mina; Muller-Delp, Judy M.; Vinogradova, Olga L.

    2015-01-01

    Conditions during spaceflight, such as the loss of the head-to-foot gravity vector, are thought to potentially alter cerebral blood flow and vascular resistance. The purpose of the present study was to determine the effects of long-term spaceflight on the functional, mechanical, and structural properties of cerebral arteries. Male C57BL/6N mice were flown 30 days in a Bion-M1 biosatellite. Basilar arteries isolated from spaceflight (SF) (n = 6), habitat control (HC) (n = 6), and vivarium control (VC) (n = 16) mice were used for in vitro functional and mechanical testing and histological structural analysis. The results demonstrate that vasoconstriction elicited through a voltage-gated Ca2+ mechanism (30–80 mM KCl) and thromboxane A2 receptors (10−8 − 3 × 10−5 M U46619) are lower in cerebral arteries from SF mice. Inhibition of Rho-kinase activity (1 μM Y27632) abolished group differences in U46619-evoked contractions. Endothelium-dependent vasodilation elicited by acetylcholine (10 μM, 2 μM U46619 preconstriction) was virtually absent in cerebral arteries from SF mice. The pressure-diameter relation was lower in arteries from SF mice relative to that in HC mice, which was not related to differences in the extracellular matrix protein elastin or collagen content or the elastin/collagen ratio in the basilar arteries. Diameter, medial wall thickness, and medial cross-sectional area of unpressurized basilar arteries were not different among groups. These results suggest that the microgravity-induced attenuation of both vasoconstrictor and vasodilator properties may limit the range of vascular control of cerebral perfusion or impair the distribution of brain blood flow during periods of stress. PMID:25593287

  19. A Survey on Aflatoxin M1 Content in Sheep and Goat Milk Produced in Sardinia Region, Italy (2005-2013).

    Science.gov (United States)

    Virdis, Salvatore; Scarano, Christian; Spanu, Vincenzo; Murittu, Gavino; Spanu, Carlo; Ibba, Ignazio; De Santis, Enrico Pietro Luigi

    2014-12-09

    In the present work the results of a survey conducted in Sardinia Region on Aflatoxin M 1 (AFM 1 ) contamination in milk of small ruminants from 2005 to 2013 are reported. A total of 517 sheep and 88 goat milk samples from bulk tank, tank trucks and silo tank milk were collected. Analyses were performed by the Regional Farmers Association laboratory using high-performance liquid chromatography following the ISO 14501:1998 standard. None of the sheep milk samples analysed during 2005-2012 showed AFM 1 contamination. In sheep milk samples collected in 2013, 8 out of 172 (4.6%) were contaminated by AFM 1 with a concentration (mean±SD) of 12.59±14.05 ng/L. In one bulk tank milk sample 58.82 ng/L AFM 1 was detected, exceeding the EU limit. In none of goat milk samples analysed from 2010 to 2012 AFM 1 was detected. In 2013, 9 out of 66 goat milk samples (13.6%) showed an AFM 1 concentration of 47.21±19.58 ng/L. Two of these samples exceeded the EU limit, with concentrations of 62.09 and 138.6 ng/L. Higher contamination frequency and concentration rates were detected in bulk tank milk samples collected at farm than in bulk milk truck or silo samples, showing a dilution effect on AFM 1 milk content along small ruminants supply chain. The rate and levels of AFM 1 contamination in sheep and goat milk samples were lower than other countries. However, the small number of milk samples analysed for AFM 1 in Sardinia Region in 2005-2013 give evidence that food business operators check programmes should be improved to ensure an adequate monitoring of AFM 1 contamination in small ruminant dairy chain.

  20. Pressure-temperature stability, Ca2+ binding, and pressure-temperature phase diagram of cod parvalbumin: Gad m 1.

    Science.gov (United States)

    Somkuti, Judit; Bublin, Merima; Breiteneder, Heimo; Smeller, László

    2012-07-31

    Fish allergy is associated with IgE-mediated hypersensitivity reactions to parvalbumins, which are small calcium-binding muscle proteins and represent the major and sole allergens for 95% of fish-allergic patients. We performed Fourier transform infrared and tryptophan fluorescence spectroscopy to explore the pressure-temperature (p-T) phase diagram of cod parvalbumin (Gad m 1) and to elucidate possible new ways of pressure-temperature inactivation of this food allergen. Besides the secondary structure of the protein, the Ca(2+) binding to aspartic and glutamic acid residues was detected. The phase diagram was found to be quite complex, containing partially unfolded and molten globule states. The Ca(2+) ions were essential for the formation of the native structure. A molten globule conformation appears at 50 °C and atmospheric pressure, which converts into an unordered aggregated state at 75 °C. At >200 MPa, only heat unfolding, but no aggregation, was observed. A pressure of 500 MPa leads to a partially unfolded state at 27 °C. The complete pressure unfolding could only be reached at an elevated temperature (40 °C) and pressure (1.14 GPa). A strong correlation was found between Ca(2+) binding and the protein conformation. The partially unfolded state was reversibly refolded. The completely unfolded molecule, however, from which Ca(2+) was released, could not refold. The heat-unfolded protein was trapped either in the aggregated state or in the molten globule state without aggregation at elevated pressures. The heat-treated and the combined heat- and pressure-treated protein samples were tested with sera of allergic patients, but no change in allergenicity was found.

  1. Plasma upflows and microwave emission in hot supra-arcade structure associated with AN M1.6 limb flare

    International Nuclear Information System (INIS)

    Kim, S.; Shibasaki, K.; Bain, H.-M.; Cho, K.-S.

    2014-01-01

    We have investigated a supra-arcade structure associated with an M1.6 flare, which occurred on the south-east limb on 2010 November 4. It is observed in EUV with the Atmospheric Imaging Assembly (AIA) on board the Solar Dynamics Observatory, microwaves at 17 and 34 GHz with the Nobeyama Radioheliograph (NoRH), and soft X-rays of 8-20 keV with RHESSI. Interestingly, we found exceptional properties of the supra-arcade thermal plasma from the AIA 131 Å and the NoRH: (1) plasma upflows along large coronal loops and (2) enhancing microwave emission. RHESSI detected two soft X-ray sources, a broad one in the middle of the supra-arcade structure and a bright one just above the flare-arcade. We estimated the number density and thermal energy for these two source regions during the decay phase of the flare. In the supra-arcade source, we found that there were increases of the thermal energy and the density at the early and last stages, respectively. On the contrary, the density and thermal energy of the source on the top of the flare-arcade decreases throughout. The observed upflows imply that there is continuous energy supply into the supra-arcade structure from below during the decay phase of the flare. It is hard to explain by the standard flare model in which the energy release site is located high in the corona. Thus, we suggest that a potential candidate of the energy source for the hot supra-arcade structure is the flare-arcade, which has exhibited a predominant emission throughout.

  2. Characterization of Novel Fusaricidins Produced by Paenibacillus polymyxa-M1 Using MALDI-TOF Mass Spectrometry

    Science.gov (United States)

    Vater, Joachim; Niu, Ben; Dietel, Kristin; Borriss, Rainer

    2015-09-01

    Paenibacillus polymyxa-M1 is a potent producer of bioactive compounds, such as lipopeptides, polyketides, and lantibiotics of biotechnological and medical interest. Genome sequencing revealed nine gene clusters for nonribosomal biosynthesis of such agents. Here we report on the investigation of the fusaricidins, a complex of cyclic lipopeptides containing 15-guanidino-3-hydroxypentadecanoic acid (GHPD) as fatty acid component by matrix-assisted laser-desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). More than 20 variants of these compounds were detected and characterized in detail. Mass spectrometric sequence analysis was performed by MALDI-LIFT-TOF/TOF fragment analysis. The obtained product ion spectra show a specific processing in the fatty acid part. GHPD is cleaved between the α- and ß-position yielding two fragments a and b, one bearing the end-standing guanidine group and another one comprising the residual two C-atoms of GHPD with the attached peptide moiety. The complete sequence of all fusaricidins was derived from sets of bn- and yn-ions. The fusaricidin complex can be divided into four lipopeptide families, three of them showing variations of the amino acid in position 3, Val or Ile for the first and Tyr or Phe for families 2 and 3, respectively. A collection of novel fusaricidins was detected differing from those of families 1-3 by an additional residue of 71 Da (family 4). LIFT-TOF/TOF fragment spectra of these species imply that in their peptide moiety, an Ala-residue is attached by an ester bond to the free hydroxyl group of Thr4. More than 10 novel fusaricidins were characterized mass spectrometrically.

  3. Chromospheric Evaporation in an M1.8 Flare Observed by the Extreme-ultraviolet Imaging Spectrometer (EIS) on Hinode

    Science.gov (United States)

    Doschek, G. A.; Warren, H. P.

    2012-12-01

    We discuss observations of chromospheric evaporation for a flare that occurred on 9 March 2012 near 03:30 UT obtained from the Extreme-ultraviolet Imaging Spectrometer (EIS) on the Hinode spacecraft. This was a multiple event with a strong energy input that reached the M1.8 class when observed by EIS. EIS was in raster mode and fortunately the slit reached almost the exact location of a significant energy input. Also, fortunately EIS obtained a full-CCD spectrum of the flare, i.e., the entire CCD was readout so that data were obtained for about the 500 lines identified in the EIS wavelength ranges. Chromospheric evaporation characterized by 150-200 km/s upflows was observed in several locations in multi-million degree spectral lines of flare ions such as Fe XXII, Fe XXIII, Fe XXIV, with simultaneous 20 - 60 km/s upflows in a host of million degree coronal lines from ions such as Fe XI - Fe XVI. The behavior of cooler, transition region ions such as O VI, Fe VIII, He II, and Fe X is more complex. At a point close to strong energy input, the flare ions reveal an isothermal source with a temperature close to 14 MK. At this point there is a strong downflow in cooler active region lines from ions such as Fe XIII and Fe XIV. Electron densities were obtained from density sensitive lines ratios from Fe XIII and Fe XIV. The results to be presented are refined from the preliminary data given above and combined with context AIA observations for a comparison with predictions of models of chromospheric evaporation as envisaged in the Standard Flare Model.

  4. Effects of muscarinic receptor antagonists on cocaine discrimination in wild-type mice and in muscarinic receptor M1, M2, and M4 receptor knockout mice.

    Science.gov (United States)

    Joseph, Lauren; Thomsen, Morgane

    2017-06-30

    Muscarinic M 1 /M 4 receptor stimulation can reduce abuse-related effects of cocaine and may represent avenues for treating cocaine addiction. Muscarinic antagonists can mimic and enhance effects of cocaine, including discriminative stimulus (S D ) effects, but the receptor subtypes mediating those effects are not known. A better understanding of the complex cocaine/muscarinic interactions is needed to evaluate and develop potential muscarinic-based medications. Here, knockout mice lacking M 1 , M 2 , or M 4 receptors (M 1 -/- , M 2 -/- , M 4 -/- ), as well as control wild-type mice and outbred Swiss-Webster mice, were trained to discriminate 10mg/kg cocaine from saline. Muscarinic receptor antagonists with no subtype selectivity (scopolamine), or preferential affinity at the M 1 , M 2 , or M 4 subtype (telenzepine, trihexyphenidyl; methoctramine, AQ-RA 741; tropicamide) were tested alone and in combination with cocaine. In intact animals, antagonists with high affinity at M 1 /M 4 receptors partially substituted for cocaine and increased the S D effect of cocaine, while M 2 -preferring antagonists did not substitute, and reduced the S D effect of cocaine. The cocaine-like effects of scopolamine were absent in M 1 -/- mice. The cocaine S D attenuating effects of methoctramine were absent in M 2 -/- mice and almost absent in M 1 -/- mice. The findings indicate that the cocaine-like S D effects of muscarinic antagonists are primarily mediated through M 1 receptors, with a minor contribution of M 4 receptors. The data also support our previous findings that stimulation of M 1 receptors and M 4 receptors can each attenuate the S D effect of cocaine, and show that this can also be achieved by blocking M 2 autoreceptors, likely via increased acetylcholine release. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. A T cell-inducing influenza vaccine for the elderly: safety and immunogenicity of MVA-NP+M1 in adults aged over 50 years.

    Directory of Open Access Journals (Sweden)

    Richard D Antrobus

    Full Text Available Current influenza vaccines have reduced immunogenicity and are of uncertain efficacy in older adults. We assessed the safety and immunogenicity of MVA-NP+M1, a viral-vectored influenza vaccine designed to boost memory T cell responses, in a group of older adults.Thirty volunteers (aged 50-85 received a single intramuscular injection of MVA-NP+M1 at a dose of 1·5×10(8 plaque forming units (pfu. Safety and immunogenicity were assessed over a period of one year. The frequency of T cells specific for nucleoprotein (NP and matrix protein 1 (M1 was determined by interferon-gamma (IFN-γ ELISpot, and their phenotypic and functional properties were characterized by polychromatic flow cytometry. In a subset of M1-specific CD8(+ T cells, T cell receptor (TCR gene expression was evaluated using an unbiased molecular approach.Vaccination with MVA-NP+M1 was well tolerated. ELISpot responses were boosted significantly above baseline following vaccination. Increases were detected in both CD4(+ and CD8(+ T cell subsets. Clonality studies indicated that MVA-NP+M1 expanded pre-existing memory CD8(+ T cells, which displayed a predominant CD27(+CD45RO(+CD57(-CCR7(- phenotype both before and after vaccination.MVA-NP+M1 is safe and immunogenic in older adults. Unlike seasonal influenza vaccination, the immune responses generated by MVA-NP+M1 are similar between younger and older individuals. A T cell-inducing vaccine such as MVA-NP+M1 may therefore provide a way to circumvent the immunosenescence that impairs routine influenza vaccination.ClinicalTrials.gov NCT00942071.

  6. Bone marrow-derived and peritoneal macrophages have different inflammatory response to oxLDL and M1/M2 marker expression

    DEFF Research Database (Denmark)

    Bisgaard, Line S; Mogensen, Christina K; Rosendahl, Alexander

    2016-01-01

    Macrophages are heterogeneous and can polarize into specific subsets, e.g. pro-inflammatory M1-like and re-modelling M2-like macrophages. To determine if peritoneal macrophages (PEMs) or bone marrow derived macrophages (BMDMs) resembled aortic macrophages from ApoE-/- mice, their M1/M2 phenotype,......, ACSL1, SRB1, DGAT1, and cpt1a) was decreased in advanced versus early lesions. In conclusion, PEMs and BMDMs are phenotypically distinct and differ from macrophages in lesions with respect to expression of M1/M2 markers and lipid metabolism genes....

  7. Removal of aflatoxin M1 from artificially contaminated yoghurt by using of new synthesized dehydroacetic acid analogues

    Directory of Open Access Journals (Sweden)

    Frane Delaš

    2012-09-01

    Full Text Available Dehydroacetic acid (DHA and its new synthesized analogues, 4-hydroxy-3-(p-toluoyl-6-(ptolyl-2H-pyrane-2-one (DHT and 5-Bromo-4-hydroxy-3-(p-toluoyl-6-(p-tolyl-2H-pyrane-2-one (BrDHT were tested for removal of aflatoxin M1 (AFM1 from artificially contaminated yoghurt with known concentrations of this toxin to determine the possible use of these chemicals as a means of controlling AFM1 accumulation. Yoghurt from cow’s milk was artificially contaminated with AFM1 at levels of 0.01 to 0.5 μg/L. Yoghurts were stored at 4 °C and 7 °C, respectively, for up to 28 days. Analysis of AFM1 in yoghurt was carried out using two dimensional thin-layer chromatography (TLC - visual estimation. The limit of detection was 0.15 ng/L. The recoveries of AFM1 from the samples spiked at levels of 10, 50, 100, and 500 ng/L were between 80.6 and 107.8 %, respectively. Concentrations of DHA and DHT of 0.01 and 0.03 μmol/L had non or little effect on AFM1 content in experimentally contaminated yoghurt, whereas concentrations higher than 0.05 μmol/L, partially inhibited AFM1 content. The percentage loss of the initial AFM1 amount in yoghurt was estimated by about 15 and 25 %, and 22 to 45 % by the end of storage, respectively. In experiments with 0.01 and 0.05 μmol/L of BrDHT or higher, the concentration of AFM1 was reduced after 28 days by 20 to 95 % or completely, respectively, depending on the time and temperature of deposit. Detection of toxicity of investigated analogues was evaluated by using the brine shrimp (Artemia salina larvae as a screening system for the determination of their sensitivity to some chemicals

  8. In-field evaluation of clinoptilolite feeding efficacy on the reduction of milk aflatoxin M1 concentration in dairy cattle

    Directory of Open Access Journals (Sweden)

    Panagiotis D. Katsoulos

    2016-06-01

    Full Text Available Abstract Background Clinoptilolite is a natural zeolite with high adsorption capacity for polar mycotoxins such as aflatoxins. The efficacy of clinoptilolite in ameliorating the toxic effects of aflatoxicosis has been proven in monogastric animals, but there is no such evidence for ruminants. The aim of this study was to evaluate, under field conditions, whether the dietary administration of clinoptilolite in dairy cows could reduce the concentration of aflatoxin M1 (AFM1 in bulk-tank milk, in farms with higher than or close to 0.05 μg/kg of milk (European maximum allowed residual level. An objective of the present study was also to investigate the effect of particle size of clinoptilolite on aflatoxin binding. Methods Fifteen commercial Greek dairy herds with AFM1 concentrations in bulk tank milk ≥0.05 μg/kg were selected. Bulk tank milk AFM1 was determined prior to the onset and on day 7 of the experiment. Clinoptilolite was added in the total mixed rations of all farms at the rate of 200 g per animal per day, throughout this period. Two different particle sizes of clinoptilolite were used; less than 0.15 mm in 9 farms (LC group and less than 0.8 mm in 6 farms (HC group. Results Clinoptilolite administration significantly reduced AFM1 concentrations in milk in all farms tested at an average rate of 56.2 % (SD: 15.11. The mean milk AFM1 concentration recorded on Day 7 was significantly (P < 0.001 lower compared to that of Day 0 (0.036 ± 0.0061 vs. 0.078 ± 0.0074 μg/kg. In LC group farms the reduction of milk AFM1 concentration was significantly higher than HC group farms (0.046 ± 0.0074 vs. 0.036 ± 0.0061 μg/kg, P = 0.002. As indicated by the Pearson correlation, there was a significant and strong linear correlation among the milk AFM1 concentrations on Days 0 and 7 (R = 0.95, P < 0.001. Conclusions Dietary administration of clinoptilolite, especially of smallest particle size, at the rate of

  9. Exposure to microgravity for 30 days onboard Bion M1 caused muscle atrophy and impaired regeneration in murine femoral Quadriceps

    Science.gov (United States)

    Radugina, E. A.; Almeida, E. A. C.; Blaber, E.; Poplinskaya, V. A.; Markitantova, Y. V.; Grigoryan, E. N.

    2018-02-01

    Mechanical unloading in microgravity during spaceflight is known to cause muscular atrophy, changes in muscle fiber composition, gene expression, and reduction in regenerative muscle growth. Although some limited data exists for long-term effects of microgravity in human muscle, these processes have mostly been studied in rodents for short periods of time. Here we report on how long-term (30-day long) mechanical unloading in microgravity affects murine muscles of the femoral Quadriceps group. To conduct these studies we used muscle tissue from 6 microgravity mice, in comparison to habitat (7), and vivarium (14) ground control mice from the NASA Biospecimen Sharing Program conducted in collaboration with the Institute for Biomedical Problems of the Russian Academy of Sciences, during the Russian Bion M1 biosatellite mission in 2013. Muscle histomorphology from microgravity specimens showed signs of extensive atrophy and regenerative hypoplasia relative to ground controls. Specifically, we observed a two-fold decrease in the number of myonuclei, compared to vivarium and ground controls, and central location of myonuclei, low density of myofibers in the tissue, and of myofibrils within a fiber, as well as fragmentation and swelling of myofibers. Despite obvious atrophy, muscle regeneration nevertheless appeared to have continued after 30 days in microgravity as evidenced by thin and short newly formed myofibers. Many of them, however, showed evidence of apoptotic cells and myofibril degradation, suggesting that long-term unloading in microgravity may affect late stages of myofiber differentiation. Ground asynchronous and vivarium control animals demonstrated normal, well-developed tissue structure with sufficient blood and nerve supply and evidence of regenerative formation of new myofibers free of apoptotic nuclei. Regenerative activity of satellite cells in muscles was observed both in microgravity and ground control groups, using Pax7 and Myogenin

  10. Glutathione S-transferase M1 null genotype: lack of association with tumour characteristics and survival in advanced breast cancer

    International Nuclear Information System (INIS)

    Lizard-Nacol, Sarab; Coudert, Bruno; Colosetti, Pascal; Riedinger, Jean-Marc; Fargeot, Pierre; Brunet-Lecomte, Patrick

    1999-01-01

    Glutathione S-transferase (GST)M1, a member of the μ class GST gene family, has been shown to be polymorphic because of a partial gene deletion. This results in a failure to express the GSTM1 gene in 50-60% of individuals. Several studies have demonstrated a possible link with the GSTM1-null genotype and susceptibility to cancer. Furthermore, a GSTM1 isoenzyme has been positively associated with protective effect against mutagenic drugs, such as alkylating agents and anthracyclines. To determine whether GSTM1 polymorphisms are associated with tumour characteristics and survival in advanced breast cancer patients, and whether it may constitute a prognostic factor. We genotyped 92 patients receiving primary chemotherapy, which included cyclophosphamide, doxorubicine and 5-fluorouracil. The relationships between allelism at GSTM1 and clinicopathological parameters including age, menopausal status, tumour size, grade hormone receptors, involved nodes and p53 gene mutations were analysed. Of the patients with GSTM1-positive genotype, tissue samples obtained before and after treatment were available from 28 cases, allowing RNA extraction and GSTM1 expression by reverse transcription polymerase chain reaction. Relationships with clinical response to chemotherapy, and disease-free and overall survival were also evaluated. The data obtained was analysed using logistic regression to estimate the odds ratio and 95% confidence interval. Of 92 patients, 57.6% (n = 53) were classified as heritably GSTM1-deficient, and 42.4% (n = 39) were of the GSTM1-positive genotype. There were no statistically significant relationships between GSTM1-null genotype and the clinicopathological parameters analysed. No relationship was observed between GSTM1 RNA expression and objective clinical response to chemotherapy. Objective clinical response to chemotherapy was related only to clinical tumour size (P = 0.0177) and to the absence of intraductal carcinoma (P = 0.0013). GSTM1-null genotype

  11. CHROMOSPHERIC EVAPORATION IN AN M1.8 FLARE OBSERVED BY THE EXTREME-ULTRAVIOLET IMAGING SPECTROMETER ON HINODE

    International Nuclear Information System (INIS)

    Doschek, G. A.; Warren, H. P.; Young, P. R.

    2013-01-01

    We discuss observations of chromospheric evaporation for a complex flare that occurred on 2012 March 9 near 03:30 UT obtained from the Extreme-ultraviolet Imaging Spectrometer (EIS) on board the Hinode spacecraft. This was a multiple event with a strong energy input that reached the M1.8 class when observed by EIS. EIS was in raster mode and fortunately the slit was almost at the exact location of a significant energy input. Also, EIS obtained a full-CCD spectrum of the flare, i.e., the entire CCD was readout so that data were obtained for about the 500 lines identified in the EIS wavelength ranges. Chromospheric evaporation characterized by 150-200 km s –1 upflows was observed in multiple locations in multi-million degree spectral lines of flare ions such as Fe XXII, Fe XXIII, and Fe XXIV, with simultaneous 20-60 km s –1 upflows in million degree coronal lines from ions such as Fe XII-Fe XVI. The behavior of cooler, transition region ions such as O VI, Fe VIII, He II, and Fe X is more complex, but upflows were also observed in Fe VIII and Fe X lines. At a point close to strong energy input in space and time, the flare ions Fe XXII, Fe XXIII, and Fe XXIV reveal an isothermal source with a temperature close to 14 MK and no strong blueshifted components. At this location there is a strong downflow in cooler active region lines from ions such as Fe XIII and Fe XIV, on the order of 200 km s –1 . We speculate that this downflow may be evidence of the downward shock produced by reconnection in the current sheet seen in MHD simulations. A sunquake also occurred near this location. Electron densities were obtained from density sensitive lines ratios from Fe XIII and Fe XIV. Atmospheric Imaging Assembly (AIA) observations from the Solar Dynamics Observatory are used with JHelioviewer to obtain a qualitative overview of the flare. However, AIA data are not presented in this paper. In summary, spectroscopic data from EIS are presented that can be used for predictive

  12. Chromospheric Evaporation in an M1.8 Flare Observed by the Extreme-ultraviolet Imaging Spectrometer on Hinode

    Science.gov (United States)

    Doschek, G. A.; Warren, H. P.; Young, P. R.

    2013-04-01

    We discuss observations of chromospheric evaporation for a complex flare that occurred on 2012 March 9 near 03:30 UT obtained from the Extreme-ultraviolet Imaging Spectrometer (EIS) on board the Hinode spacecraft. This was a multiple event with a strong energy input that reached the M1.8 class when observed by EIS. EIS was in raster mode and fortunately the slit was almost at the exact location of a significant energy input. Also, EIS obtained a full-CCD spectrum of the flare, i.e., the entire CCD was readout so that data were obtained for about the 500 lines identified in the EIS wavelength ranges. Chromospheric evaporation characterized by 150-200 km s-1 upflows was observed in multiple locations in multi-million degree spectral lines of flare ions such as Fe XXII, Fe XXIII, and Fe XXIV, with simultaneous 20-60 km s-1 upflows in million degree coronal lines from ions such as Fe XII-Fe XVI. The behavior of cooler, transition region ions such as O VI, Fe VIII, He II, and Fe X is more complex, but upflows were also observed in Fe VIII and Fe X lines. At a point close to strong energy input in space and time, the flare ions Fe XXII, Fe XXIII, and Fe XXIV reveal an isothermal source with a temperature close to 14 MK and no strong blueshifted components. At this location there is a strong downflow in cooler active region lines from ions such as Fe XIII and Fe XIV, on the order of 200 km s-1. We speculate that this downflow may be evidence of the downward shock produced by reconnection in the current sheet seen in MHD simulations. A sunquake also occurred near this location. Electron densities were obtained from density sensitive lines ratios from Fe XIII and Fe XIV. Atmospheric Imaging Assembly (AIA) observations from the Solar Dynamics Observatory are used with JHelioviewer to obtain a qualitative overview of the flare. However, AIA data are not presented in this paper. In summary, spectroscopic data from EIS are presented that can be used for predictive tests of

  13. The Role of Primary Motor Cortex (M1) Glutamate and GABA Signaling in l-DOPA-Induced Dyskinesia in Parkinsonian Rats.

    Science.gov (United States)

    Lindenbach, David; Conti, Melissa M; Ostock, Corinne Y; George, Jessica A; Goldenberg, Adam A; Melikhov-Sosin, Mitchell; Nuss, Emily E; Bishop, Christopher

    2016-09-21

    Long-term treatment of Parkinson's disease with l-DOPA almost always leads to the development of involuntary movements termed l-DOPA-induced dyskinesia. Whereas hyperdopaminergic signaling in the basal ganglia is thought to cause dyskinesia, alterations in primary motor cortex (M1) activity are also prominent during dyskinesia, suggesting that the cortex may represent a therapeutic target. The present study used the rat unilateral 6-hydroxydopamine lesion model of Parkinson's disease to characterize in vivo changes in GABA and glutamate neurotransmission within M1 and determine their contribution to behavioral output. 6-Hydroxydopamine lesion led to parkinsonian motor impairment that was partially reversed by l-DOPA. Among sham-lesioned rats, l-DOPA did not change glutamate or GABA efflux. Likewise, 6-hydroxydopamine lesion did not impact GABA or glutamate among rats chronically treated with saline. However, we observed an interaction of lesion and treatment whereby, among lesioned rats, l-DOPA given acutely (1 d) or chronically (14-16 d) reduced glutamate efflux and enhanced GABA efflux. Site-specific microinjections into M1 demonstrated that l-DOPA-induced dyskinesia was reduced by M1 infusion of a D1 antagonist, an AMPA antagonist, or a GABAA agonist. Overall, the present study demonstrates that l-DOPA-induced dyskinesia is associated with increased M1 inhibition and that exogenously enhancing M1 inhibition may attenuate dyskinesia, findings that are in agreement with functional imaging and transcranial magnetic stimulation studies in human Parkinson's disease patients. Together, our study suggests that increasing M1 inhibitory tone is an endogenous compensatory response designed to limit dyskinesia severity and that potentiating this response is a viable therapeutic strategy. Most Parkinson's disease patients will receive l-DOPA and eventually develop hyperkinetic involuntary movements termed dyskinesia. Such symptoms can be as debilitating as the disease

  14. Effects of a novel encapsulating technique on the temperature tolerance and anti-colitis activity of the probiotic bacterium Lactobacillus kefiranofaciens M1.

    Science.gov (United States)

    Wang, Sheng-Yao; Ho, Yi-Fang; Chen, Yen-Po; Chen, Ming-Ju

    2015-04-01

    Lactobacillus kefiranofaciens M1 (M1) has been shown to possess many different beneficial health effects including anti-colitis activity. The purpose of this study was to develop a novel and easily scaled-up encapsulating technique that would improve the temperature tolerance of the bacterium and reduce the sensitivity of the organism to gastrointestinal fluid. A mixture of sodium alginate, gellan gum and skim milk powder was used as a coating material to entrap M1. The M1 gel was then directly freeze dried in order to dehydrate the covering and form microcapsules. The viable cell numbers of M1 present only dropped ten folds after the freeze-drying encapsulation process. The viable cell counts remained constant at 5 × 10(7) CFU/g after heating from 25 °C to 75 °C and holding at 75 °C for 1 min. The viable cell counts were reduced to 10(6) CFU/g and 10(5) CFU/g after 8-week storage at 4 °C and subsequent heat treatment with simulated gastrointestinal fluid test (SGFT) and bile salts, respectively. The effect of encapsulated M1 on the organism's anti-colitis activity was evaluated using the dextran sodium sulfate (DSS) induced colitis mouse model. An in vivo study indicated that administration of heat treated encapsulated M1 was able to ameliorate DSS-induced colitis producing a significant reduction in the bleeding score and an attenuation of inflammatory score. These findings clearly demonstrate that encapsulation of M1 using this novel technique is able to provide good protection from temperature changes and SGFT treatment and also does not affect the organism's anti-colitis activity. Copyright © 2014 Elsevier Ltd. All rights reserved.

  15. Cyclic GMP-dependent protein kinase II is necessary for macrophage M1 polarization and phagocytosis via toll-like receptor 2.

    Science.gov (United States)

    Liao, Wei-Ting; You, Huey-Ling; Li, Changgui; Chang, Jan-Gowth; Chang, Shun-Jen; Chen, Chung-Jen

    2015-05-01

    Cyclic GMP-dependent protein kinase II (cGKII; PRKG2) phosphorylates a variety of biological targets and has been identified as a gout-susceptible gene. However, the regulatory role of cGKII in triggering gout disease has yet to be clarified. Thus, we plan to explore the specific function of cGKII in macrophages related to gout disease. By using cGKII gene knockdown method, we detected macrophage M1/M2 polarization, phagocytosis, and their responses to stimulation by monosodium urate (MSU). cGKII was highly expressed in M1 phenotype, but not in M2, and cGKII knockdown significantly inhibited macrophage M1 polarization by decreasing M1 chemokine markers (CXCL10 and CCL2) and downregulating phagocytosis function. We further identified that cGKII-associated phagocytosis was mediated by upregulating toll-like receptor 2 (TLR2) expression, but not by TLR4. Mimicking gout condition by MSU treatments, we found that MSU alone induced cGKII and TLR2 expression with increased M1 polarization markers and phagocytosis activity. It means that cGKII knockdown significantly inhibited this MSU-induced cGKII-TLR2-phagocytosis axis. Our study showed that cGKII plays a key role in M1 polarization, especially in TLR2-mediated phagocytosis under MSU exposure. The findings provide evidence for the possible role of cGKII as an inflammation exciter in gout disease. Gout-susceptible gene cGKII is necessary for macrophage M1 polarization. cGKII regulates M1 phagocytosis function via TLR2. Monosodium urate treatments increase cGKII expression and related function. This study reveals the role of cGKII in enhancing gouty inflammatory responses.

  16. III. The effect of various doses of gamma 6OCo radiation upon pollen vitality of China aster (Callistephus chinensis Nees in M1 and M2 generation

    Directory of Open Access Journals (Sweden)

    Alicja Wosińska

    2013-12-01

    Full Text Available The effect of gamma radiation upon pollen was studied in populations of 4 China aster varieties in M1 (plants from irradiated seeds and M2 generation. Effect of radiation Was assessed·in partiicular years. Comparison was rnalde between pollen vitality in irradiated plants and in the control. Effect of radiation was visibly harmful only in case of plants from M1 generation. The effects of radiation were different for particular varieties.

  17. Exosomes from M1-Polarized Macrophages Potentiate the Cancer Vaccine by Creating a Pro-inflammatory Microenvironment in the Lymph Node.

    Science.gov (United States)

    Cheng, Lifang; Wang, Yuhua; Huang, Leaf

    2017-07-05

    Exosomes are small membrane-bound vesicular particles generated by most cells for intercellular communication and regulation. During biogenesis, specific lipids, RNAs, proteins, and carbohydrates are enriched and packaged into the vesicles so that the exosomal contents reflect not only the source but also the physiological conditions of the parental cells. These exosomes transport materials or signals to the target cells for diverse physiological purposes. Our study focused on the exosomes derived from M1-polarized, proinflammatory macrophages for the possibility of using M1 exosomes as an immunopotentiator for a cancer vaccine. The M1 exosomes displayed a tropism toward lymph nodes after subcutaneous injection, primarily taken up by the local macrophages and dendritic cells, and they induced the release of a pool of Th1 cytokines. We found that M1, but not M2, exosomes enhanced activity of lipid calcium phosphate (LCP) nanoparticle-encapsulated Trp2 vaccine, and they induced a stronger antigen-specific cytotoxic T cell response. The M1 exosomes proved to be a more potent immunopotentiator than CpG oligonucleotide when used with LCP nanoparticle vaccine in a melanoma growth inhibition study. Thus, our study indicated that exosomes derived from M1-polarized macrophages could be used as a vaccine adjuvant. Copyright © 2017 The American Society of Gene and Cell Therapy. Published by Elsevier Inc. All rights reserved.

  18. Structural basis for the inhibition of M1 family aminopeptidases by the natural product actinonin: Crystal structure in complex with E. coli aminopeptidase N.

    Science.gov (United States)

    Ganji, Roopa Jones; Reddi, Ravikumar; Gumpena, Rajesh; Marapaka, Anil Kumar; Arya, Tarun; Sankoju, Priyanka; Bhukya, Supriya; Addlagatta, Anthony

    2015-05-01

    Actinonin is a pseudotripeptide that displays a high affinity towards metalloproteases including peptide deformylases (PDFs) and M1 family aminopeptidases. PDF and M1 family aminopeptidases belong to thermolysin-metzincin superfamily. One of the major differences in terms of substrate binding pockets between these families is presence (in M1 aminopeptidases) or absence (in PDFs) of an S1 substrate pocket. The binding mode of actinonin to PDFs has been established previously; however, it is not clear how the actinonin, without a P1 residue, would bind to the M1 aminopeptidases. Here we describe the crystal structure of Escherichia coli aminopeptidase N (ePepN), a model protein of the M1 family aminopeptidases in complex with actinonin. For comparison we have also determined the structure of ePepN in complex with a well-known tetrapeptide inhibitor, amastatin. From the comparison of the actinonin and amastatin ePepN complexes, it is clear that the P1 residue is not critical as long as strong metal chelating head groups, like hydroxamic acid or α-hydroxy ketone, are present. Results from this study will be useful for the design of selective and efficient hydroxamate inhibitors against M1 family aminopeptidases. © 2015 The Protein Society.

  19. In situ hybridization on the change of m1 receptor mRNA in different brain areas of aged rats and the effect of Yin tonic Zhimu studied

    International Nuclear Information System (INIS)

    Hu Yaer; Xia Zongqin; Yi Ningyu

    1996-01-01

    The change of gene expression of m1 receptors in different brain areas of aged rats and the effects of water extract of the Yin tonic Zhimu and its active principle ZMS was studied. In situ hybridization using 35 S-labelled m1 and m2 probes and analysis of the autoradiographs using a computerized image-analyzer was selected. The grain density of m1 mRNA in striatum was significantly lowered in old rats as compared with young rats (decreased by 12.26 +- 3.60, P<0.01). Long-term oral administration of ZMS, the active principle of Yin tonic Zhimu but not the water extraction of Zhimu, elevated the m1 mRNA in striatum of aged rats (increased by 15.71 +- 3.27, P<0.01). Neither significant change of the grain density of m1 mRNA in old rats nor significant effect of Zhimu or ZMS was observed in cerebral cortex and hippocampus. The m1 mRNA level in striatum is decreased in aged rats and ZMS is able to elevate it

  20. Cortico-cortical white matter motor pathway microstructure is related to psychomotor retardation in major depressive disorder.

    Directory of Open Access Journals (Sweden)

    Tobias Bracht

    Full Text Available Alterations of brain structure and function have been associated with psychomotor retardation in major depressive disorder (MDD. However, the association of motor behaviour and white matter integrity of motor pathways in MDD is unclear. The aim of the present study was to first investigate structural connectivity of white matter motor pathways in MDD. Second, we explore the relation of objectively measured motor activity and white matter integrity of motor pathways in MDD. Therefore, 21 patients with MDD and 21 healthy controls matched for age, gender, education and body mass index underwent diffusion tensor imaging and 24 hour actigraphy (measure of the activity level the same day. Applying a probabilistic fibre tracking approach we extracted connection pathways between the dorsolateral prefrontal cortex (dlPFC, the rostral anterior cingulate cortex (rACC, the pre-supplementary motor area (pre-SMA, the SMA-proper, the primary motor cortex (M1, the caudate nucleus, the putamen, the pallidum and the thalamus. Patients had lower activity levels and demonstrated increased mean diffusivity (MD in pathways linking left pre-SMA and SMA-proper, and right SMA-proper and M1. Exploratory analyses point to a positive association of activity level and mean-fractional anisotropy in the right rACC-pre-SMA connection in MDD. Only MDD patients with low activity levels had a negative linear association of activity level and mean-MD in the left dlPFC-pre-SMA connection. Our results point to structural alterations of cortico-cortical white matter motor pathways in MDD. Altered white matter organisation of rACC-pre-SMA and dlPFC-pre-SMA pathways may contribute to movement initiation in MDD.

  1. [Role of immune-related GTPase M1 in cortical neurons autophagy of mice with sepsis-induced brain injury].

    Science.gov (United States)

    Huang, Qun; Chen, Bin; Li, Yafei; Li, Xihong

    2017-12-28

    To investigate the role of immune-related GTPase M1 (IRGM1) in cortical neurons autophagy in mice with sepsis induced brain injury (SIBI).
 Methods: Sixty wild-type C57BL/6 mice and sixty IRGM1 gene knockout C57BL/6 mice were randomly divided into 4 groups: a sham-operated wild-type (SWT) group, a cecal ligation and puncture (CLP) model wild-type (MWT) group, a sham-operated knockout (SKO) group, and a CLP model knockout (MKO) group. Models of mice with sepsis were established by CLP. Six hours of after CLP, the neurobehavioral scores for mice were recorded. The mice were diagnosed with SIBI and enrolled for the studies in next step if the neurobehavioral score was less than 6 in the MWT and MKO groups. The sham operation group only opened the abdominal cavity without CLP. Pathological changes in mouse cerebral cortex were observed by HE staining. Electron microscope was used to observe the ultrastructure of autophagy in cortical neurons. The expression of IRGM1 and INF-γ mRNA in the cerebral cortex of mice were detected by Real time quantitative PCR. The protein expression of microtubule-associated protein 1 light chain 3 (LC3)-II, LC3-I, sequestosome-1 (SQSTM1) and IRGM1 were measured by Western blot. Immunofluorescence staining was used to examine the expression of IRGM1 in mouse cortical neurons.
 Results: In the MWT group, the cortical neurons showed dilated endoplasmic reticulum, swelling mitochondria, and increased number of autophagosomes after 6 or 24 h of CLP in contrast to the SWT group. At 6 h after CLP, the expression of LC3-II in the cerebral cortex began to up-regulate, and the up-regulation was maintained till 96 h after CLP; on the contrary, SQSTM1 began to decline after 6 h of CLP. Compared with SWT group, IRGM1 was strongly up-regulated in the cerebral cortex of mice at both mRNA and protein levels in the MWT group after 12 h of CLP, and the mRNA expression of IFN-γ was also increased significantly (PSIBI was 90% (27/30) in the MWT group

  2. Chromospheric evaporation flows and density changes deduced from Hinode/EIS during an M1.6 flare

    Science.gov (United States)

    Gömöry, P.; Veronig, A. M.; Su, Y.; Temmer, M.; Thalmann, J. K.

    2016-04-01

    Aims: We study the response of the solar atmosphere during a GOES M1.6 flare using spectroscopic and imaging observations. In particular, we examine the evolution of the mass flows and electron density together with the energy input derived from hard X-ray (HXR) in the context of chromospheric evaporation. Methods: We analyzed high-cadence sit-and-stare observations acquired with the Hinode/EIS spectrometer in the Fe xiii 202.044 Å (log T = 6.2) and Fe xvi 262.980 Å (log T = 6.4) spectral lines to derive temporal variations of the line intensity, Doppler shifts, and electron density during the flare. We combined these data with HXR measurements acquired with RHESSI to derive the energy input to the lower atmosphere by flare-accelerated electrons. Results: During the flare impulsive phase, we observe no significant flows in the cooler Fe xiii line but strong upflows, up to 80-150 km s-1, in the hotter Fe xvi line. The largest Doppler shifts observed in the Fe xvi line were co-temporal with the sharp intensity peak. The electron density obtained from a Fe xiii line pair ratio exhibited fast increase (within two minutes) from the pre-flare level of 5.01 × 109 cm-3 to 3.16 × 1010 cm-3 during the flare peak. The nonthermal energy flux density deposited from the coronal acceleration site to the lower atmospheric layers during the flare peak was found to be 1.34 × 1010 erg s-1 cm-2 for a low-energy cut-off that was estimated to be 16 keV. During the decline flare phase, we found a secondary intensity and density peak of lower amplitude that was preceded by upflows of ~15 km s-1 that were detected in both lines. The flare was also accompanied by a filament eruption that was partly captured by the EIS observations. We derived Doppler velocities of 250-300 km s-1 for the upflowing filament material. Conclusions: The spectroscopic results for the flare peak are consistent with the scenario of explosive chromospheric evaporation, although a comparatively low value of the

  3. The M1 form of tumor-associated macrophages in non-small cell lung cancer is positively associated with survival time

    International Nuclear Information System (INIS)

    Ma, Junliang; Liu, Lunxu; Che, Guowei; Yu, Nanbin; Dai, Fuqiang; You, Zongbing

    2010-01-01

    Tumor-associated macrophages (TAMs) play an important role in growth, progression and metastasis of tumors. In non-small cell lung cancer (NSCLC), TAMs' anti-tumor or pro-tumor role is not determined. Macrophages are polarized into M1 (with anti-tumor function) and M2 (with pro-tumor function) forms. This study was conducted to determine whether the M1 and M2 macrophage densities in NSCLC are associated with patient's survival time. Fifty patients with an average of 1-year survival (short survival group) and 50 patients with an average of 5-year survival (long survival group) were included in this retrospective study. Paraffin-embedded NSCLC specimens and their clinicopathological data including up to 8-year follow-up information were used. Immunohistochemical double-staining of CD68/HLA-DR (markers for M1 macrophages) and CD68/CD163 (markers for M2 macrophages) was performed and evaluated in a blinded fashion. The M1 and M2 macrophage densities in the tumor islets, stroma, or islets and stroma were determined using computer-aided microscopy. Correlation of the macrophage densities and patient's survival time was analyzed using the Statistical Package for the Social Sciences. Approximately 70% of TAMs were M2 macrophages and the remaining 30% were M1 macrophages in NSCLC. The M2 macrophage densities (approximately 78 to 113 per mm 2 ) in the tumor islets, stroma, or islets and stroma were not significantly different between the long survival and short survival groups. The M1 macrophage densities in the tumor islets (approximately 70/mm 2 ) and stroma (approximately 34/mm 2 ) of the long survival group were significantly higher than the M1 macrophage densities in the tumor islets (approximately 7/mm 2 ) and stroma (13/mm 2 ) of the short survival group (P < 0.001 and P < 0.05, respectively). The M2 macrophage densities were not associated with patient's survival time. The M1 macrophage densities in the tumor islets, stroma, or islets and stroma

  4. Effects of muscarinic M1 and M4 acetylcholine receptor stimulation on extinction and reinstatement of cocaine seeking in male mice, independent of extinction learning.

    Science.gov (United States)

    Stoll, Kevin; Hart, Rachel; Lindsley, Craig W; Thomsen, Morgane

    2018-03-01

    Stimulating muscarinic M 1 /M 4 receptors can blunt reinforcing and other effects of cocaine. A hallmark of addiction is continued drug seeking/craving after abstinence and relapse. We tested whether stimulating M 1 and/or M 4 receptors could facilitate extinction of cocaine seeking, and whether this was mediated via memory consolidation. Experimentally naïve C57BL/6J mice were allowed to acquire self-administration of intravenous cocaine (1 mg/kg/infusion) under a fixed-ratio 1 schedule of reinforcement. Then, saline was substituted for cocaine until responding extinguished to ≤30% of cocaine-reinforced responding. Immediately after each extinction session, mice received saline, the M 1 /M 4 receptor-preferring agonist xanomeline, the M 1 receptor-selective allosteric agonist VU0357017, the M 4 receptor-selective positive allosteric modulator VU0152100, or VU0357017 + VU0152100. In additional experiments, xanomeline was administered delayed after the session or in the home cage before extinction training began. In the latter group, reinstatement of responding by a 10-mg/kg cocaine injection was also tested. Stimulating M 1  + M 4 receptors significantly expedited extinction from 17.2 sessions to 8.3 using xanomeline or 7.8 using VU0357017 + VU0152100. VU0357017 alone and VU0152100 alone did not significantly modify rates of extinction (12.6 and 14.6 sessions). The effect of xanomeline was fully preserved when administered delayed after or unpaired from extinction sessions (7.5 and 6.4 sessions). Xanomeline-treated mice showed no cocaine-induced reinstatement. These findings show that M 1 /M 4 receptor stimulation can decrease cocaine seeking in mice. The effect lasted beyond treatment duration and was not dependent upon extinction learning. This suggests that M 1 /M 4 receptor stimulation modulated or reversed some neurochemical effects of cocaine exposure.

  5. Pathological Ace2-to-Ace enzyme switch in the stressed heart is transcriptionally controlled by the endothelial Brg1–FoxM1 complex

    Science.gov (United States)

    Yang, Jin; Feng, Xuhui; Zhou, Qiong; Cheng, Wei; Shang, Ching; Han, Pei; Lin, Chiou-Hong; Chen, Huei-Sheng Vincent; Quertermous, Thomas; Chang, Ching-Pin

    2016-01-01

    Genes encoding angiotensin-converting enzymes (Ace and Ace2) are essential for heart function regulation. Cardiac stress enhances Ace, but suppresses Ace2, expression in the heart, leading to a net production of angiotensin II that promotes cardiac hypertrophy and fibrosis. The regulatory mechanism that underlies the Ace2-to-Ace pathological switch, however, is unknown. Here we report that the Brahma-related gene-1 (Brg1) chromatin remodeler and forkhead box M1 (FoxM1) transcription factor cooperate within cardiac (coronary) endothelial cells of pathologically stressed hearts to trigger the Ace2-to-Ace enzyme switch, angiotensin I-to-II conversion, and cardiac hypertrophy. In mice, cardiac stress activates the expression of Brg1 and FoxM1 in endothelial cells. Once activated, Brg1 and FoxM1 form a protein complex on Ace and Ace2 promoters to concurrently activate Ace and repress Ace2, tipping the balance to Ace2 expression with enhanced angiotensin II production, leading to cardiac hypertrophy and fibrosis. Disruption of endothelial Brg1 or FoxM1 or chemical inhibition of FoxM1 abolishes the stress-induced Ace2-to-Ace switch and protects the heart from pathological hypertrophy. In human hypertrophic hearts, BRG1 and FOXM1 expression is also activated in endothelial cells; their expression levels correlate strongly with the ACE/ACE2 ratio, suggesting a conserved mechanism. Our studies demonstrate a molecular interaction of Brg1 and FoxM1 and an endothelial mechanism of modulating Ace/Ace2 ratio for heart failure therapy. PMID:27601681

  6. Diversification of the vacAs1m1 and vacAs2m2 strains of Helicobacter pylori in Meriones unguiculatus

    Directory of Open Access Journals (Sweden)

    Sandra Mendoza Elizalde

    2016-11-01

    Full Text Available The bacterium Helicobacter pylori exhibits great genetic diversity, and the pathogenic roles of its virulence factors have been widely studied. However, the evolutionary dynamics of H. pylori strains during stomach colonization are not well characterized. Here, we analyzed the microevolutionary dynamics of the toxigenic strain vacAs1m1, the non-toxigenic strain vacAs2m2, and a combination of both strains in an animal model over time. Meriones unguiculatus were inoculated with the following bacteria: group 1–toxigenic strain vacAs1m1/cagA+/cagE+/babA2+; ST181, group 2–non-toxigenic strain vacAs2m2/ cagA+/ cagE+/ babA2+; ST2901, and group 3–both strains. The gerbils were euthanized at different time points (3, 6, 12 and 18 months. In group 1, genetic alterations were observed at 6 and 12 months. With the combination of both strains, group 3 also exhibited genetic alterations at 3 and 18 months; moreover, a chimera, vacA m1-m2, was detected. Additionally, four new sequence types (STs were reported in the PubMLST database for H. pylori. Synonymous and non-synonymous mutations were analyzed and associated with alterations in amino acids. Microevolutionary analysis of the STs (PHYLOViZ identified in each group revealed many mutational changes in the toxigenic (vacAs1m1 and non-toxigenic (vacAs2m2 strains. Phylogenetic assessments (eBURST did not reveal clonal complexes. Our findings indicate that the toxigenic strain, vacAs1m1, and a combination of toxigenic and non-toxigenic strains acquired genetic material by recombination. The allelic combination, vacAs2m1, displayed the best adaptation in the animal model over time, and a chimera, m1-m2, was also identified, which confirmed previous reports.

  7. Effects of heat, cold, acid and bile salt adaptations on the stress tolerance and protein expression of kefir-isolated probiotic Lactobacillus kefiranofaciens M1.

    Science.gov (United States)

    Chen, Ming-Ju; Tang, Hsin-Yu; Chiang, Ming-Lun

    2017-09-01

    Lactobacillus kefiranofaciens M1 is a probiotic strain isolated from Taiwanese kefir grains. The present study evaluated the effects of heat, cold, acid and bile salt adaptations on the stress tolerance of L. kefiranofaciens M1. The regulation of protein expression of L. kefiranofaciens M1 under these adaptation conditions was also investigated. The results showed that adaptation of L. kefiranofaciens M1 to heat, cold, acid and bile salts induced homologous tolerance and cross-protection against heterologous challenge. The extent of induced tolerance varied depending on the type and condition of stress. Proteomic analysis revealed that 27 proteins exhibited differences in expression between non-adapted and stress-adapted L. kefiranofaciens M1 cells. Among these proteins, three proteins involved in carbohydrate metabolism (triosephosphate isomerase, enolase and NAD-dependent glycerol-3-phosphate dehydrogenase), two proteins involved in pH homeostasis (ATP synthase subunits AtpA and AtpB), two stress response proteins (chaperones DnaK and GroEL) and one translation-related protein (30S ribosomal protein S2) were up-regulated by three of the four adaptation treatments examined. The increased synthesis of these stress proteins might play a critical protective role in the cellular defense against heat, cold, acid and bile salt stresses. Copyright © 2017 Elsevier Ltd. All rights reserved.

  8. Genomic comparison of the endophyte Herbaspirillum seropedicae SmR1 and the phytopathogen Herbaspirillum rubrisubalbicans M1 by suppressive subtractive hybridization and partial genome sequencing.

    Science.gov (United States)

    Monteiro, Rose A; Balsanelli, Eduardo; Tuleski, Thalita; Faoro, Helison; Cruz, Leonardo M; Wassem, Roseli; de Baura, Valter A; Tadra-Sfeir, Michelle Z; Weiss, Vinícius; DaRocha, Wanderson D; Muller-Santos, Marcelo; Chubatsu, Leda S; Huergo, Luciano F; Pedrosa, Fábio O; de Souza, Emanuel M

    2012-05-01

    Herbaspirillum rubrisubalbicans M1 causes the mottled stripe disease in sugarcane cv. B-4362. Inoculation of this cultivar with Herbaspirillum seropedicae SmR1 does not produce disease symptoms. A comparison of the genomic sequences of these closely related species may permit a better understanding of contrasting phenotype such as endophytic association and pathogenic life style. To achieve this goal, we constructed suppressive subtractive hybridization (SSH) libraries to identify DNA fragments present in one species and absent in the other. In a parallel approach, partial genomic sequence from H. rubrisubalbicans M1 was directly compared in silico with the H. seropedicae SmR1 genome. The genomic differences between the two organisms revealed by SSH suggested that lipopolysaccharide and adhesins are potential molecular factors involved in the different phenotypic behavior. The cluster wss probably involved in cellulose biosynthesis was found in H. rubrisubalbicans M1. Expression of this gene cluster was increased in H. rubrisubalbicans M1 cells attached to the surface of maize root, and knockout of wssD gene led to decrease in maize root surface attachment and endophytic colonization. The production of cellulose could be responsible for the maize attachment pattern of H. rubrisubalbicans M1 that is capable of outcompeting H. seropedicae SmR1. © 2012 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

  9. Temperature-dependent Raman and ultraviolet photoelectron spectroscopy studies on phase transition behavior of VO{sub 2} films with M1 and M2 phases

    Energy Technology Data Exchange (ETDEWEB)

    Okimura, Kunio, E-mail: okifn@keyaki.cc.u-tokai.ac.jp; Hanis Azhan, Nurul [Graduate School of Engineering, Tokai University, Hiratsuka 259-1292 (Japan); Hajiri, Tetsuya [UVSOR Facility, Institute for Molecular Science, Okazaki 444-8585 (Japan); Graduate School of Engineering, Nagoya University, Nagoya 464-8603 (Japan); Kimura, Shin-ichi [UVSOR Facility, Institute for Molecular Science, Okazaki 444-8585 (Japan); Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871 (Japan); Zaghrioui, Mustapha; Sakai, Joe [GREMAN, UMR 7347 CNRS, Université François Rabelais de Tours, Parc de Grandmont, 37200 Tours (France)

    2014-04-21

    Structural and electronic phase transitions behavior of two polycrystalline VO{sub 2} films, one with pure M1 phase and the other with pure M2 phase at room temperature, were investigated by temperature-controlled Raman spectroscopy and ultraviolet photoelectron spectroscopy (UPS). We observed characteristic transient dynamics in which the Raman modes at 195 cm{sup −1} (V-V vibration) and 616 cm{sup −1} (V-O vibration) showed remarkable hardening along the temperature in M1 phase film, indicating the rearrangements of V-V pairs and VO{sub 6} octahedra. It was also shown that the M1 Raman mode frequency approached those of invariant M2 peaks before entering rutile phase. In UPS spectra with high energy resolution of 0.03 eV for the M2 phase film, narrower V{sub 3d} band was observed together with smaller gap compared to those of M1 phase film, supporting the nature of Mott insulator of M2 phase even in the polycrystalline film. Cooperative behavior of lattice rearrangements and electronic phase transition was suggested for M1 phase film.

  10. Internal (m=1, n=1) and (m=2, n=1) resistive modes in the toroidal tokamak with circular cross-section

    International Nuclear Information System (INIS)

    Bussac, M.N.; Pellat, R.; Edery, D.; Soule, J.L.

    1977-01-01

    A linear analysis is presented of the toroidal coupling between the internal resistive modes (m=1, n=1) and (m=2, n=1) in the tokamak with circular cross-section. The resistive and diamagnetic effects are included in the singular layers where the safety factor q takes respectively the values one and two. By expanding the MHD equations in powers of epsilon, the local inverse of the aspect ratio, a system of two coupled equations is obtained for the harmonic amplitudes. When the shear is finite on q=1 the toroidal coupling is negligible. In the opposite limit, one can explain (a) the experimental behaviour of the (m=1, n=1) mode before the internal disruption, and (b) the simultaneous observation of the modes (m=1, n=1) and (m=2, n=1) before the main disruption. (author)

  11. Room Temperature Optical Constants and Band Gap Evolution of Phase Pure M1-VO2 Thin Films Deposited at Different Oxygen Partial Pressures by Reactive Magnetron Sputtering

    Directory of Open Access Journals (Sweden)

    Meng Jiang

    2014-01-01

    Full Text Available Spectroscopic ellipsometry study was employed for phase pure VO2(M1 thin films grown at different oxygen partial pressures by reactive magnetron sputtering. The optical constants of the VO2(M1 thin films have been determined in a photon energy range between 0.73 and 5.05 eV. The near-infrared extinction coefficient and optical conductivity of VO2(M1 thin films rapidly increase with decreasing O2-Ar ratios. Moreover, two electronic transitions can be uniquely assigned. The energy gaps correlated with absorption edge (E1 at varied O2-Ar ratios are almost the same (~2.0 eV; consequently, the absorption edge is not significantly changed. However, the optical band gap corresponding to semiconductor-to-metal phase transition (E2 decreases from 0.53 to 0.18 eV with decreasing O2-Ar ratios.

  12. Identification and Validation of a Potent Dual Inhibitor of the P. falciparum M1 and M17 Aminopeptidases Using Virtual Screening.

    Directory of Open Access Journals (Sweden)

    Chiara Ruggeri

    Full Text Available The Plasmodium falciparum PfA-M1 and PfA-M17 metalloaminopeptidases are validated drug targets for the discovery of antimalarial agents. In order to identify dual inhibitors of both proteins, we developed a hierarchical virtual screening approach, followed by in vitro evaluation of the highest scoring hits. Starting from the ZINC database of purchasable compounds, sequential 3D-pharmacophore and molecular docking steps were applied to filter the virtual 'hits'. At the end of virtual screening, 12 compounds were chosen and tested against the in vitro aminopeptidase activity of both PfA-M1 and PfA-M17. Two molecules showed significant inhibitory activity (low micromolar/nanomolar range against both proteins. Finally, the crystal structure of the most potent compound in complex with both PfA-M1 and PfA-M17 was solved, revealing the binding mode and validating our computational approach.

  13. Amphipathic alpha-helices and putative cholesterol binding domains of the influenza virus matrix M1 protein are crucial for virion structure organisation.

    Science.gov (United States)

    Tsfasman, Tatyana; Kost, Vladimir; Markushin, Stanislav; Lotte, Vera; Koptiaeva, Irina; Bogacheva, Elena; Baratova, Ludmila; Radyukhin, Victor

    2015-12-02

    The influenza virus matrix M1 protein is an amphitropic membrane-associated protein, forming the matrix layer immediately beneath the virus raft membrane, thereby ensuring the proper structure of the influenza virion. The objective of this study was to elucidate M1 fine structural characteristics, which determine amphitropic properties and raft membrane activities of the protein, via 3D in silico modelling with subsequent mutational analysis. Computer simulations suggest the amphipathic nature of the M1 α-helices and the existence of putative cholesterol binding (CRAC) motifs on six amphipathic α-helices. Our finding explains for the first time many features of this protein, particularly the amphitropic properties and raft/cholesterol binding potential. To verify these results, we generated mutants of the A/WSN/33 strain via reverse genetics. The M1 mutations included F32Y in the CRAC of α-helix 2, W45Y and W45F in the CRAC of α-helix 3, Y100S in the CRAC of α-helix 6, M128A and M128S in the CRAC of α-helix 8 and a double L103I/L130I mutation in both a putative cholesterol consensus motif and the nuclear localisation signal. All mutations resulted in viruses with unusual filamentous morphology. Previous experimental data regarding the morphology of M1-gene mutant influenza viruses can now be explained in structural terms and are consistent with the pivotal role of the CRAC-domains and amphipathic α-helices in M1-lipid interactions. Copyright © 2015 Elsevier B.V. All rights reserved.

  14. Evidence for {open_quotes}magnetic rotation{close_quotes} in nuclei: New results on the M1-bands of {sup 198,199}Pb

    Energy Technology Data Exchange (ETDEWEB)

    Clark, R.M. [Lawrence Berkeley National Lab., CA (United States)

    1996-12-31

    Lifetimes of states in four of the M1-bands in {sup 198,199}Pb have been determined through a Doppler Shift Attenuation Method measurement performed using the Gammasphere array. The deduced B(M1) values, which are a sensitive probe of the underlying mechanism for generating these sequences, show remarkable agreement with Tilted Axis Cranking (TAC) calculations. Evidence is also presented for the possible termination of the bands. The results represent clear evidence for a new concept in nuclear excitations: {open_quote}magnetic rotation{close_quote}.

  15. Insights into Watson-Crick/Hoogsteen breathing dynamics and damage repair from the solution structure and dynamic ensemble of DNA duplexes containing m1A.

    Science.gov (United States)

    Sathyamoorthy, Bharathwaj; Shi, Honglue; Zhou, Huiqing; Xue, Yi; Rangadurai, Atul; Merriman, Dawn K; Al-Hashimi, Hashim M

    2017-05-19

    In the canonical DNA double helix, Watson-Crick (WC) base pairs (bps) exist in dynamic equilibrium with sparsely populated (∼0.02-0.4%) and short-lived (lifetimes ∼0.2-2.5 ms) Hoogsteen (HG) bps. To gain insights into transient HG bps, we used solution-state nuclear magnetic resonance spectroscopy, including measurements of residual dipolar couplings and molecular dynamics simulations, to examine how a single HG bp trapped using the N1-methylated adenine (m1A) lesion affects the structural and dynamic properties of two duplexes. The solution structure and dynamic ensembles of the duplexes reveals that in both cases, m1A forms a m1A•T HG bp, which is accompanied by local and global structural and dynamic perturbations in the double helix. These include a bias toward the BI backbone conformation; sugar repuckering, major-groove directed kinking (∼9°); and local melting of neighboring WC bps. These results provide atomic insights into WC/HG breathing dynamics in unmodified DNA duplexes as well as identify structural and dynamic signatures that could play roles in m1A recognition and repair. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  16. Insights into Watson–Crick/Hoogsteen breathing dynamics and damage repair from the solution structure and dynamic ensemble of DNA duplexes containing m1A

    Science.gov (United States)

    Sathyamoorthy, Bharathwaj; Shi, Honglue; Zhou, Huiqing; Xue, Yi; Rangadurai, Atul; Merriman, Dawn K.

    2017-01-01

    Abstract In the canonical DNA double helix, Watson–Crick (WC) base pairs (bps) exist in dynamic equilibrium with sparsely populated (∼0.02–0.4%) and short-lived (lifetimes ∼0.2–2.5 ms) Hoogsteen (HG) bps. To gain insights into transient HG bps, we used solution-state nuclear magnetic resonance spectroscopy, including measurements of residual dipolar couplings and molecular dynamics simulations, to examine how a single HG bp trapped using the N1-methylated adenine (m1A) lesion affects the structural and dynamic properties of two duplexes. The solution structure and dynamic ensembles of the duplexes reveals that in both cases, m1A forms a m1A•T HG bp, which is accompanied by local and global structural and dynamic perturbations in the double helix. These include a bias toward the BI backbone conformation; sugar repuckering, major-groove directed kinking (∼9°); and local melting of neighboring WC bps. These results provide atomic insights into WC/HG breathing dynamics in unmodified DNA duplexes as well as identify structural and dynamic signatures that could play roles in m1A recognition and repair. PMID:28369571

  17. The interaction of glutathione S-transferase M1-null variants with tobacco smoke exposure and the development of childhood asthma

    DEFF Research Database (Denmark)

    Rogers, A J; Brasch-Andersen, C; Ionita-Laza, I

    2009-01-01

    BACKGROUND: The glutathione S-transferase M1 (GSTM1)-null variant is a common copy number variant associated with adverse pulmonary outcomes, including asthma and airflow obstruction, with evidence of important gene-by-environment interactions with exposures to oxidative stress. OBJECTIVE: To exp...

  18. The dynamics processes of the soil microbecenosis to condition of radionuclides contamination under influence of agent 'Bajkal EhM-1'

    International Nuclear Information System (INIS)

    Shchur, A.V.; Vetoshkina, S.N.; Chernukha, G.A.; Shipilov, Yu.V.; Val'ko, O.V.

    2006-01-01

    Used of the preparation 'Bajkal EhM-1' influences to number of micro-organisms species in microbecenosis and it's popularity were increase. The general pool and biomass of the micro-organisms have a share in the process of the bio dynamics and transformation of an organic matter of the soil experimental plot were increase. (authors)

  19. An ultra-sensitive monoclonal antibody-based fluorescent microsphere immunochromatographic test strip assay for detecting aflatoxin M1 in milk

    Science.gov (United States)

    A rapid lateral flow fluorescent microspheres immunochromatography test strip (FMs-ICTS) has been developed for the detection of aflatoxin M1 (AFM1) residues in milk. For this purpose, an ultra-sensitive anti-AFM1 monoclonal antibody (MAb) 1D3 was prepared and identified. The IC50 value of the MA...

  20. Protein kinase D stabilizes aldosterone-induced ERK1/2 MAP kinase activation in M1 renal cortical collecting duct cells to promote cell proliferation.

    LENUS (Irish Health Repository)

    McEneaney, Victoria

    2010-01-01

    Aldosterone elicits transcriptional responses in target tissues and also rapidly stimulates the activation of protein kinase signalling cascades independently of de novo protein synthesis. Here we investigated aldosterone-induced cell proliferation and extra-cellular regulated kinase 1 and 2 (ERK1\\/2) mitogen activated protein (MAP) kinase signalling in the M1 cortical collecting duct cell line (M1-CCD). Aldosterone promoted the proliferative growth of M1-CCD cells, an effect that was protein kinase D1 (PKD1), PKCdelta and ERK1\\/2-dependent. Aldosterone induced the rapid activation of ERK1\\/2 with peaks of activation at 2 and 10 to 30 min after hormone treatment followed by sustained activation lasting beyond 120 min. M1-CCD cells suppressed in PKD1 expression exhibited only the early, transient peaks in ERK1\\/2 activation without the sustained phase. Aldosterone stimulated the physical association of PKD1 with ERK1\\/2 within 2 min of treatment. The mineralocorticoid receptor (MR) antagonist RU28318 inhibited the early and late phases of aldosterone-induced ERK1\\/2 activation, and also aldosterone-induced proliferative cell growth. Aldosterone induced the sub-cellular redistribution of ERK1\\/2 to the nuclei at 2 min and to cytoplasmic sites, proximal to the nuclei after 30 min. This sub-cellular distribution of ERK1\\/2 was inhibited in cells suppressed in the expression of PKD1.

  1. Dynamics in prophage content of invasive and noninvasive M1 and M28 Streptococcus pyogenes isolates in the Netherlands from 1959 to 1996

    NARCIS (Netherlands)

    Vlaminckx, B.J.M.; Schuren, F.H.J.; Montijn, R.C.; Caspers, M.P.M.; Beitsma, M.M.; Wannet, W.J.B.; Schouls, L.M.; Verhoef, J.; Jansen, W.T.M.

    2007-01-01

    Invasive group A streptococcal (GAS) disease reemerged in The Netherlands in the late 1980s. To seek an explanation for this resurgence, the genetic compositions of 22 M1 and 19 M28 GAS strains isolated in The Netherlands between 1960s and the mid-1990s were analyzed by using a mixed-genome DNA

  2. ACCUMULATION OF M1DG DNA ADDUCTS AFTER CHRONIC EXPOSURE TO PCBS, BUT NOT FROM ACUTE EXPOSURE TO DIOXIN-LIKE COMPOUNDS

    Science.gov (United States)

    ABSTRACT: Oxidative DNA damage is one of the key events leading to mutation and cancer. The present study examined the accumulation of M1dG DNA adducts, 3-(2’-deoxy-β-D-erythro-pentofuranosyl)-pyrimido[1,2-a]-purin-10(3H)-one, after single or yearly exposur...

  3. Cyclic AMP is a key regulator of M1 to M2a phenotypic conversion of microglia in the presence of Th2 cytokines.

    Science.gov (United States)

    Ghosh, Mousumi; Xu, Yong; Pearse, Damien D

    2016-01-13

    Microglia and macrophages play a central role in neuroinflammation. Pro-inflammatory cytokines trigger their conversion to a classically activated (M1) phenotype, sustaining inflammation and producing a cytotoxic environment. Conversely, anti-inflammatory cytokines polarize the cells towards an alternatively activated (M2), tissue reparative phenotype. Elucidation of the signal transduction pathways involved in M1 to M2 phenotypic conversion may provide insight into how the innate immune response can be harnessed during distinct phases of disease or injury to mediate neuroprotection and neurorepair. Microglial cells (cell line and primary) were subjected to combined cyclic adenosine monophosphate (cyclic AMP) and IL-4, or either alone, in the presence of pro-inflammatory mediators, lipopolysaccharide (LPS), or tumor necrosis factor-α (TNF-α). Their effects on the expression of characteristic markers for M1 and M2 microglia were assessed. Similarly, the M1 and M2 phenotypes of microglia and macrophages within the lesion site were then evaluated following a contusive spinal cord injury (SCI) to the thoracic (T8) spinal cord of rats and mice when the agents were administered systemically. It was demonstrated that cyclic AMP functions synergistically with IL-4 to promote M1 to M2 conversion of microglia in culture. The combination of cyclic AMP and IL-4, but neither alone, induced an Arg-1(+)/iNOS(-)cell phenotype with concomitant expression of other M2-specific markers including TG2 and RELM-α. M2-converted microglia showed ameliorated production of pro-inflammatory cytokines (TNF-α and IP-10) and reactive oxygen species, with no alteration in phagocytic properties. M2a conversion required protein kinase A (PKA), but not the exchange protein directly activated by cyclic AMP (EPAC). Systemic delivery of cyclic AMP and IL-4 after experimental SCI also promoted a significant M1 to M2a phenotypic change in microglia and macrophage population dynamics in the lesion

  4. Long-term activation upon brief exposure to xanomleline is unique to M1 and M4 subtypes of muscarinic acetylcholine receptors.

    Directory of Open Access Journals (Sweden)

    Eva Šantrůčková

    Full Text Available Xanomeline is an agonist endowed with functional preference for M1/M4 muscarinic acetylcholine receptors. It also exhibits both reversible and wash-resistant binding to and activation of these receptors. So far the mechanisms of xanomeline selectivity remain unknown. To address this question we employed microfluorometric measurements of intracellular calcium levels and radioligand binding to investigate differences in the short- and long-term effects of xanomeline among muscarinic receptors expressed individually in Chinese hamster ovary cells. 1/One-min exposure of cells to xanomeline markedly increased intracellular calcium at hM1 and hM4, and to a lesser extent at hM2 and hM3 muscarinic receptors for more than 1 hour. 2/Unlike the classic agonists carbachol, oxotremorine, and pilocarpine 10-min exposure to xanomeline did not cause internalization of any receptor subtype. 3/Wash-resistant xanomeline selectively prevented further increase in intracellular calcium by carbachol at hM1 and hM4 receptors. 4/After transient activation xanomeline behaved as a long-term antagonist at hM5 receptors. 5/The antagonist N-methylscopolamine (NMS reversibly blocked activation of hM1 through hM4 receptors by xanomeline. 6/NMS prevented formation of xanomeline wash-resistant binding and activation at hM2 and hM4 receptors and slowed them at hM1, hM3 and hM5 receptors. Our results show commonalities of xanomeline reversible and wash-resistant binding and short-time activation among the five muscarinic receptor subtypes. However long-term receptor activation takes place in full only at hM1 and hM4 receptors. Moreover xanomeline displays higher efficacy at hM1 and hM4 receptors in primary phasic intracellular calcium release. These findings suggest the existence of particular activation mechanisms specific to these two receptors.

  5. Molecular characterisation of a calmodulin gene, VcCaM1, that is differentially expressed under aluminium stress in highbush blueberry.

    Science.gov (United States)

    Inostroza-Blancheteau, C; Aquea, F; Loyola, R; Slovin, J; Josway, S; Rengel, Z; Reyes-Díaz, M; Alberdi, M; Arce-Johnson, P

    2013-11-01

    Calmodulin (CaM), a small acidic protein, is one of the best characterised Ca(2+) sensors in eukaryotes. This Ca(2+) -regulated protein plays a critical role in decoding and transducing environmental stress signals by activating specific targets. Many environmental stresses elicit changes in intracellular Ca(2+) activity that could initiate adaptive responses under adverse conditions. We report the first molecular cloning and characterisation of a calmodulin gene, VcCaM1 (Vaccinium corymbosum Calmodulin 1), in the woody shrub, highbush blueberry. VcCaM1 was first identified as VCAL19, a gene induced by aluminium stress in V. corymbosum L. A full-length cDNA of VcCaM1 containing a 766-bp open reading frame (ORF) encoding 149 amino acids was cloned from root RNA. The sequence encodes four Ca(2+) -binding motifs (EF-hands) and shows high similarity (99%) with the isoform CaM 201 of Daucus carota. Expression analyses showed that following Al treatment, VcCaM1 message level decreased in roots of Brigitta, an Al-resistant cultivar, and after 48 h, was lower than in Bluegold, an Al-sensitive cultivar. VcCAM1 message also decreased in leaves of both cultivars within 2 h of treatment. Message levels in leaves then increased by 24 h to control levels in Brigitta, but not in Bluegold, but then decreased again by 48 h. In conclusion, VcCaM1 does not appear to be directly involved in Al resistance, but may be involved in improved plant performance under Al toxicity conditions through regulation of Ca(2+) homeostasis and antioxidant systems in leaves. © 2013 German Botanical Society and The Royal Botanical Society of the Netherlands.

  6. Long non-coding RNA cox-2 prevents immune evasion and metastasis of hepatocellular carcinoma by altering M1/M2 macrophage polarization.

    Science.gov (United States)

    Ye, Yibiao; Xu, Yunxiuxiu; Lai, Yu; He, Wenguang; Li, Yanshan; Wang, Ruomei; Luo, Xinxi; Chen, Rufu; Chen, Tao

    2018-03-01

    Macrophages have been shown to demonstrate a high level of plasticity, with the ability to undergo dynamic transition between M1 and M2 polarized phenotypes. We investigate long non-coding RNA (lncRNA) cox-2 in macrophage polarization and the regulatory mechanism functions in hepatocellular carcinoma (HCC). Lipopolysaccharide (LPS) was used to induce RAW264.7 macrophages into M1 type, and IL-4 was to induce RAW264.7 macrophages into M2 type. We selected mouse hepatic cell line Hepal-6 and hepatoma cell line HepG2 for co-incubation with M1 or M2 macrophages. Quantitative real-time PCR was used to detect the expressions of lncRNA cox-2 and mRNAs. ELISA was conducted for testing IL-12 and IL-10 expressions; Western blotting for epithelial mesenchymal transition related factors (E-cadherin and Vimentin). An MTT, colony formation assay, flow cytometry, transwell assay, and stretch test were conducted to test cell abilities. The M1 macrophages had higher lncRNA cox-2 expression than that in the non-polarized macrophages and M2 macrophages. The lncRNA cox-2 siRNA decreased the expression levels of IL-12, iNOS, and TNF-α in M1 macrophages, increased the expression levels of IL-10, Arg-1, and Fizz-1 in M2 macrophages (all P evasion and tumor growth by inhibiting the polarization of M2 macrophages. © 2017 Wiley Periodicals, Inc.

  7. Regulation of Human Macrophage M1–M2 Polarization Balance by Hypoxia and the Triggering Receptor Expressed on Myeloid Cells-1

    Directory of Open Access Journals (Sweden)

    Federica Raggi

    2017-09-01

    Full Text Available Macrophages (Mf are a heterogeneous population of tissue-resident professional phagocytes and a major component of the leukocyte infiltrate at sites of inflammation, infection, and tumor growth. They can undergo diverse forms of activation in response to environmental factors, polarizing into specialized functional subsets. A common hallmark of the pathologic environment is represented by hypoxia. The impact of hypoxia on human Mf polarization has not been fully established. The objective of this study was to elucidate the effects of a hypoxic environment reflecting that occurring in vivo in diseased tissues on the ability of human Mf to polarize into classically activated (proinflammatory M1 and alternatively activated (anti-inflammatory M2 subsets. We present data showing that hypoxia hinders Mf polarization toward the M1 phenotype by decreasing the expression of T cell costimulatory molecules and chemokine homing receptors and the production of proinflammatory, Th1-priming cytokines typical of classical activation, while promoting their acquisition of phenotypic and secretory features of alternative activation. Furthermore, we identify the triggering receptor expressed on myeloid cells (TREM-1, a member of the Ig-like immunoregulatory receptor family, as a hypoxia-inducible gene in Mf and demonstrate that its engagement by an agonist Ab reverses the M2-polarizing effect of hypoxia imparting a M1-skewed phenotype to Mf. Finally, we provide evidence that Mf infiltrating the inflamed hypoxic joints of children affected by oligoarticular juvenile idiopatic arthritis express high surface levels of TREM-1 associated with predominant M1 polarization and suggest the potential of this molecule in driving M1 proinflammatory reprogramming in the hypoxic synovial environment.

  8. Spatial structure peculiarities of influenza A virus matrix M1 protein in an acidic solution that simulates the internal lysosomal medium.

    Science.gov (United States)

    Shishkov, Alexander; Bogacheva, Elena; Fedorova, Natalia; Ksenofontov, Alexander; Badun, Gennadii; Radyukhin, Victor; Lukashina, Elena; Serebryakova, Marina; Dolgov, Alexey; Chulichkov, Alexey; Dobrov, Evgeny; Baratova, Lyudmila

    2011-12-01

    The structure of the C-terminal domain of the influenza virus A matrix M1 protein, for which X-ray diffraction data were still missing, was studied in acidic solution. Matrix M1 protein was bombarded with thermally-activated tritium atoms, and the resulting intramolecular distribution of the tritium label was analyzed to assess the steric accessibility of the amino acid residues in this protein. This technique revealed that interdomain loops and the C-terminal domain of the protein are the most accessible to labeling with tritium atoms. A model of the spatial arrangement of the C-terminal domain of matrix M1 protein was generated using rosetta software adjusted to the data obtained by tritium planigraphy experiments. This model suggests that the C-terminal domain is an almost flat layer with a three-α-helical structure. To explain the high level of tritium label incorporation into the C-terminal domain of the M1 protein in an acidic solution, we also used independent experimental approaches (CD spectroscopy, limited proteolysis and MALDI-TOF MS analysis of the proteolysis products, dynamic light scattering and analytical ultracentrifugation), as well as multiple computational algorithms, to analyse the intrinsic protein disorder. Taken together, the results obtained in the present study indicate that the C-terminal domain is weakly structured. We hypothesize that the specific 3D structural peculiarities of the M1 protein revealed in acidic pH solution allow the protein greater structural flexibility and enable it to interact effectively with the components of the host cell. © 2011 The Authors Journal compilation © 2011 FEBS.

  9. Regulation of Human Macrophage M1–M2 Polarization Balance by Hypoxia and the Triggering Receptor Expressed on Myeloid Cells-1

    Science.gov (United States)

    Raggi, Federica; Pelassa, Simone; Pierobon, Daniele; Penco, Federica; Gattorno, Marco; Novelli, Francesco; Eva, Alessandra; Varesio, Luigi; Giovarelli, Mirella; Bosco, Maria Carla

    2017-01-01

    Macrophages (Mf) are a heterogeneous population of tissue-resident professional phagocytes and a major component of the leukocyte infiltrate at sites of inflammation, infection, and tumor growth. They can undergo diverse forms of activation in response to environmental factors, polarizing into specialized functional subsets. A common hallmark of the pathologic environment is represented by hypoxia. The impact of hypoxia on human Mf polarization has not been fully established. The objective of this study was to elucidate the effects of a hypoxic environment reflecting that occurring in vivo in diseased tissues on the ability of human Mf to polarize into classically activated (proinflammatory M1) and alternatively activated (anti-inflammatory M2) subsets. We present data showing that hypoxia hinders Mf polarization toward the M1 phenotype by decreasing the expression of T cell costimulatory molecules and chemokine homing receptors and the production of proinflammatory, Th1-priming cytokines typical of classical activation, while promoting their acquisition of phenotypic and secretory features of alternative activation. Furthermore, we identify the triggering receptor expressed on myeloid cells (TREM)-1, a member of the Ig-like immunoregulatory receptor family, as a hypoxia-inducible gene in Mf and demonstrate that its engagement by an agonist Ab reverses the M2-polarizing effect of hypoxia imparting a M1-skewed phenotype to Mf. Finally, we provide evidence that Mf infiltrating the inflamed hypoxic joints of children affected by oligoarticular juvenile idiopatic arthritis express high surface levels of TREM-1 associated with predominant M1 polarization and suggest the potential of this molecule in driving M1 proinflammatory reprogramming in the hypoxic synovial environment. PMID:28936211

  10. Rugged Ozone Sterilization System Model M1 (ROSS M1)

    Science.gov (United States)

    2017-07-13

    13. SUPPLEMENTARY NOTES Cleared, 88PA, Case # 2017-3765, 1 Aug 2017. 14. ABSTRACT Contaminated surgical instruments may result in secondary...surgical instruments are free of contamination and that critical surgeries can be performed in a timely manner. Special Operations Surgical Teams...literature, predicate technology, Food and Drug Administration (FDA) guidance, and industry standards provided a plan for design verification, validation

  11. EPA protects against muscle damage in the mdx mouse model of Duchenne muscular dystrophy by promoting a shift from the M1 to M2 macrophage phenotype.

    Science.gov (United States)

    Carvalho, Samara Camaçari de; Apolinário, Leticia Montanholi; Matheus, Selma Maria Michelin; Santo Neto, Humberto; Marques, Maria Julia

    2013-11-15

    In dystrophic mdx mice and in Duchenne muscular dystrophy, inflammation contributes to myonecrosis. Previously, we demonstrated that eicosapentaenoic acid (EPA) decreased inflammation and necrosis in dystrophic muscle. In the present study, we examined the effects of EPA and the corticoid deflazacort (DFZ) as modulators of M1 (iNOS-expressing cells) and M2 (CD206-expressing cells) macrophages. Mdx mice (14 days old) received EPA or DFZ for 16 days. The diaphragm, biceps brachii and quadriceps muscles were studied. Immunofluorescence, immunoblotting and ELISA assays showed that EPA increased interleucin-10, reduced interferon-γ and was more effective than DFZ in promoting a shift from M1 to M2. © 2013.

  12. Calculation of M1-excitations in the 42Ca, 44Ca and 54Fe with allowance for the 1p 1h * phonon configurations

    International Nuclear Information System (INIS)

    Kamerdzhiev, S.P.; Tkachev, V.N.

    1988-01-01

    The microscopic model of account of 1p1hx phonon configurations is used to describe M1-excitations in 42 Ca, 44 Ca and 54 Fe 1f 7/2 -shell. The most low-lying and more collectivized electrical phonons are taken into account. The Boron-Mottelson collective model with parameters obtained in the experiment is used to describe them. The calculation results are compared with calculations on other models. A set of all data allows to make the supposition that the deficient part of M1-resonance force in nuclei of 1f 7/2 -shell should be distributed on low-intensive 1 + -levels in the wide range of the nucleon binding energy

  13. Some properties of tetravalent actinide phosphates of M1M42(PO4)3 type and peculiarities of their structure

    International Nuclear Information System (INIS)

    Burnaeva, A.A.; Volkov, Yu.F.; Kryukova, A.I.; Skiba, O.V.; Spiryakov, V.I.; Korshunov, I.A.; Samojlova, T.K.

    1987-01-01

    Generalizing analysis of data on crystallographic and IR spectral properties of double phosphates of actinide and alkali elements of M (1) M 2 (4) (PO 4 ) 3 type is conducted. It is shown, that Li - , Na - , K - , Rb - , CsTh 2 (PO 4 ) 3 , Li - , Na - , KU 2 (PO 4 ) 3 , NaNp 2 (PO 4 ) 3 compounds crystallize in a monoclinic type structure and form an isostructural phosphate series. It is ascertained, that in rubidium-uranium, uranium-cesium systems double salt formation is not observed. Plutonium-sodium phosphate has a rhombic-type structure, which points out to the existence of a morphotropic transition in NaM 2 4 (PO 4 ) 3 phosphate series at the Np-Pu boundary. Some regularities of structure and effect of M 1 and M 4 nature on the double phosphate structure are revealed

  14. Double-scaling limits of random matrices and minimal (2m, 1) models: the merging of two cuts in a degenerate case

    International Nuclear Information System (INIS)

    Marchal, O; Cafasso, M

    2011-01-01

    In this paper, we show that the double-scaling-limit correlation functions of a random matrix model when two cuts merge with degeneracy 2m (i.e. when y ∼ x 2m for arbitrary values of the integer m) are the same as the determinantal formulae defined by conformal (2m, 1) models. Our approach follows the one developed by Bergère and Eynard in (2009 arXiv:0909.0854) and uses a Lax pair representation of the conformal (2m, 1) models (giving a Painlevé II integrable hierarchy) as suggested by Bleher and Eynard in (2003 J. Phys. A: Math. Gen. 36 3085). In particular we define Baker–Akhiezer functions associated with the Lax pair in order to construct a kernel which is then used to compute determinantal formulae giving the correlation functions of the double-scaling limit of a matrix model near the merging of two cuts

  15. Double-scaling limits of random matrices and minimal (2m, 1) models: the merging of two cuts in a degenerate case

    Science.gov (United States)

    Marchal, O.; Cafasso, M.

    2011-04-01

    In this paper, we show that the double-scaling-limit correlation functions of a random matrix model when two cuts merge with degeneracy 2m (i.e. when y ~ x2m for arbitrary values of the integer m) are the same as the determinantal formulae defined by conformal (2m, 1) models. Our approach follows the one developed by Bergère and Eynard in (2009 arXiv:0909.0854) and uses a Lax pair representation of the conformal (2m, 1) models (giving a Painlevé II integrable hierarchy) as suggested by Bleher and Eynard in (2003 J. Phys. A: Math. Gen. 36 3085). In particular we define Baker-Akhiezer functions associated with the Lax pair in order to construct a kernel which is then used to compute determinantal formulae giving the correlation functions of the double-scaling limit of a matrix model near the merging of two cuts.

  16. Characterization of IncN plasmids carrying blaCTX-M-1 and qnr genes in Escherichia coli and Salmonella from animals, the environment and humans

    DEFF Research Database (Denmark)

    Dolejska, Monika; Villa, Laura; Hasman, Henrik

    2013-01-01

    were compared using restriction fragment length polymorphism (RFLP), plasmid multilocus sequence typing (pMLST) and hybridization with repN, qnrS1, qnrB19 or blaCTX-M-1 probes. Plasmids pKT58A and pHHA45 were sequenced using the 454-Genome Sequencer FLX platform on a library constructed from plasmid...... DNA purified from the respective E. coli transformants.Results Three types of IncN plasmids carrying blaCTX-M-1, qnrS1 and qnrB19 genes were identified in strains isolated from the Czech Republic, Poland, Slovakia, Denmark, Italy and the Netherlands, corresponding to pMLST sequence type (ST) 1, ST3...

  17. Some basic theorems on the cross-sums of certain class of numbers (M-1) when the operations are done with different bases M of the arithmetic

    International Nuclear Information System (INIS)

    Ozoemena, P.C.; Onwumechili, C.A.

    1988-11-01

    Some new theorems have been propounded for the numbers (M-1), as they relate to other numerals, through the basic arithmetical operations, at different bases M. For some reason, we give the proof of the theorems for the case M=10 using mathematical induction, and by Peano's fifth axiom make our generalizations. Comments are made in respect of the numbers (M-1), (in this case 9). Apart from our theorems facilitating mathematical operations, evidences have also been given, from different sources of the interesting properties of this class of numbers, represented in our own case by the numeral 9. The theorems neither violate the divisibility rule for 9 nor are they a consequence of it. From symmetry, a suggestion is made in respect of the possible origin of the numeration in base 10, and the case of a ten dimensional Universe reconsidered. (author). 18 refs, 1 fig., 4 tabs

  18. USPIO-labeling in M1 and M2-polarized macrophages: An in vitro study using a clinical magnetic resonance scanner.

    Science.gov (United States)

    Zini, Chiara; Venneri, Mary A; Miglietta, Selenia; Caruso, Damiano; Porta, Natale; Isidori, Andrea M; Fiore, Daniela; Gianfrilli, Daniele; Petrozza, Vincenzo; Laghi, Andrea

    2018-08-01

    Aim of the study was to evaluate USPIO labeling in different macrophage populations using a clinical 3.0T MR unit with optical and electron microscopy as the gold standard. Human monocytic cell line THP-1 cells were differentiated into macrophages. Afterwards, M0 macrophages were incubated with IL-4 and IL-13 in order to obtain M2 polarized macrophages or with IFN-gamma and LPS for classical macrophage activation (M1). These groups were incubated with USPIO-MR contrast agent (P904) for 36 hr; M0, M0 + P904, M1 +  P904, and M2 + P904 were analyzed in gel phantoms with a 3.0T MR scanner. m-RNA of M1 and M2 markers confirmed the polarization of THP-1-derived macrophages. M2 + P904 showed a much higher T1 signal (p <  0.0001), a significantly lower (p < 0.0001) T2* signal, and significantly higher R* (p < 0.0001) compared to the other populations. Hystological analysis confirmed higher iron content in the M2-polarized population compared to both M1-polarized (p = 0.04) and M0-P904 (p = 0.003). Ultrastructure analysis demonstrated ubiquitous localization of P904 within the cellular compartments. Our results demonstrate that a selective USPIO-labeling of different macrophage populations can be detected in vitro using the 3.0T clinical scanner. © 2017 Wiley Periodicals, Inc.

  19. An ir study of M(1-propanethiol)2Ni(CN)4.G (M=Cd,Ni and G=benzene) clathrates

    International Nuclear Information System (INIS)

    Kartal, Z.; Tuerkoz, D.; Bahceli, S.

    2004-01-01

    Two Hofmann-propanethiol-type clathrates of the for M(1-propanethiol) 2 Ni(CN) 4 .G (M=Cd or Ni; G = benzene) have been prepared in the powder form. The 1-propanethiol (1-PT) molecules provide the cavities in which the quest benzene molecules in clathrate structure ar accommodated. The infrared investigations of the obtained clathrates indicate that these compounds are similar in structure to the other Hofmann-type clathrates (Authors)

  20. Progesterone therapy induces an M1 to M2 switch in microglia phenotype and suppresses NLRP3 inflammasome in a cuprizone-induced demyelination mouse model.

    Science.gov (United States)

    Aryanpour, Roya; Pasbakhsh, Parichehr; Zibara, Kazem; Namjoo, Zeinab; Beigi Boroujeni, Fatemeh; Shahbeigi, Saeed; Kashani, Iraj Ragerdi; Beyer, Cordian; Zendehdel, Adib

    2017-10-01

    Demyelination of the central nervous system (CNS) has been associated to reactive microglia in neurodegenerative disorders, such as multiple sclerosis (MS). The M1 microglia phenotype plays a pro-inflammatory role while M2 is involved in anti-inflammatory processes in the brain. In this study, CPZ-induced demyelination mouse model was used to investigate the effect of progesterone (PRO) therapy on microglia activation and neuro-inflammation. Results showed that progesterone therapy (CPZ+PRO) decreased neurological behavioral deficits, as demonstrated by significantly decreased escape latencies, in comparison to CPZ mice. In addition, CPZ+PRO caused a significant reduction in the mRNA expression levels of M1-markers (iNOS, CD86, MHC-II and TNF-α) in the corpus callosum region, whereas the expression of M2-markers (Trem-2, CD206, Arg-1 and TGF-β) was significantly increased, in comparison to CPZ mice. Moreover, CPZ+PRO resulted in a significant decrease in the number of iNOS + and Iba-1 + /iNOS + cells (M1), whereas TREM-2 + and Iba-1 + /TREM-2 + cells (M2) significantly increased, in comparison to CPZ group. Furthermore, CPZ+PRO caused a significant decrease in mRNA and protein expression levels of NLRP3 and IL-18 (~2-fold), in comparison to the CPZ group. Finally, CPZ+PRO therapy was accompanied with reduced levels of demyelination, compared to CPZ, as confirmed by immunofluorescence to myelin basic protein (MBP) and Luxol Fast Blue (LFB) staining, as well as transmission electron microscopy (TEM) analysis. In summary, we reported for the first time that PRO therapy causes polarization of M2 microglia, attenuation of M1 phenotype, and suppression of NLRP3 inflammasome in a CPZ-induced demyelination model of MS. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. One-loop corrections of orders (Zα)6m1/m2 and (Zα)7 to the fine structure of muonium

    International Nuclear Information System (INIS)

    Martynenko, A.P.; Faustov, R.N.

    2003-01-01

    Corrections of orders (Zα) 6 m 1 /m 2 and (Zα) 7 from one-loop two-photon amplitudes to the energy spectra of hydrogen-like atoms are calculated by expanding the relevant integrand in a Taylor series. A method for averaging the resulting quasipotential in the d-dimensional coordinate representation is formulated. Numerical values are obtained for the corresponding contributions to the fine structure of the muonium, hydrogen, and positronium atoms

  2. Critical opalescence of the pion field and the M1 form factor of 12C: An investigation of the role of the rho meson

    International Nuclear Information System (INIS)

    Delorme, J.; Figureau, A.; Giraud, N.

    1980-01-01

    It is shown that the inelastic M1 form factor of 12 C can be interpreted by nuclear polarization phenomena with inclusion of the rho meson in the polarizing interaction playing an essential role at large momenta. Whereas much of the observed anomaly can be attributed to standard core polarization effects, a large opalescence of the pion field (a factor 4.5 enhancement) would be needed to get full agreement with experiment. (orig.)

  3. Critical opalescence of the pion field and the M1 form factor of 12C: an investigation of the role of the rho meson

    International Nuclear Information System (INIS)

    Delorme, J.; Figureau, A.; Giraud, A.

    1979-11-01

    It is shown that the inelastic M1 form factor of 12 C can be interpreted by nuclear polarization phenomena with inclusion of the rho meson in the polarizing interaction playing an essential role at large momenta. Whereas much of the observed anomaly can be attributed to standard core polarization effects, a large opalescence of the pion field (a factor 4.5 enhancement) would be needed to get full agreement with experiment

  4. M1 mirror print-through investigation and performance on the thermo-opto-mechanical testbed for the Space Interferometry Mission

    Science.gov (United States)

    Feria, V. Alfonso; Lam, Jonathan; Van Buren, Dave

    2006-06-01

    SIM PlanetQuest (SIM) is a large (9-meter baseline) space-borne optical interferometer that will determine the position and distance of stars to high accuracy. With microarcsecond measurements SIM will probe nearby stars for Earth-sized planets. To achieve this precision, SIM requires very tight manufacturing tolerances and high stability of optical components. To reduce technical risks, the SIM project developed an integrated thermal, mechanical and optical testbed (TOM3) to allow predictions of the system performance at the required high precision. The TOM3 testbed used full-scale brassboard optical components and picometer-class metrology to reach the SIM target performance levels. During the testbed integration and after one of the testbed mirrors, M1, was bonded into its mount, some surface distortion dimples that exceeded the optical specification were discovered. A detailed finite element model was used to analyze different load cases to try to determine the source of the M1 surface deformations. The same model was also used to compare with actual deformations due to varied thermal conditions on the TOM3 testbed. This paper presents the studies carried out to determine the source of the surface distortions on the M1 mirror as well as comparison and model validation during testing. This research was carried out at the Jet Propulsion Laboratory, California Institute of Technology, under a contract with the National Aeronautics and Space Administration.

  5. Classification of acute myeloid leukemia subtypes M1, M2 and M3 using active contour without edge segmentation and momentum backpropagation artificial neural network

    Directory of Open Access Journals (Sweden)

    Harjoko Agus

    2018-01-01

    Full Text Available Acute Myeloid Leukemia (AML is a type of cancer which attacks white blood cells from myeloid. AML has eight subtypes, namely: M0, M1, M2, M3, M4, M5, M6, and M7. AML subtypes M1, M2 and M3 are affected by the same type of cells, myeloblast, making it needs more detailed analysis to distinguish. To overcome these obstacles, this research is applying digital image processing with Active Contour Without Edge (ACWE and Momentum Backpropagation artificial neural network for AML subtypes M1, M2 and M3 classification based on the type of the cell. Six features required as training parameters from every cell obtained by using feature extraction. The features are: cell area, perimeter, circularity, nucleus ratio, mean and standard deviation. The results show that ACWE can be used for segmenting white blood cells with 83.789% success percentage of 876 total cell objects. The whole AML slides had been identified according to the cell types predicted number through training with momentum backpropagation. Five times testing calibration with the best parameter generated averages value of 84.754% precision, 75.887% sensitivity, 95.090% specificity and 93.569% accuracy.

  6. Importance of Leu99 in transmembrane segment M1 of the Na+, K+ -ATPase in the binding and occlusion of K+

    DEFF Research Database (Denmark)

    Einholm, Anja P.; Andersen, Jens Peter; Vilsen, Bente

    2007-01-01

    Twenty-six point mutations were introduced into the N-terminal and middle parts of transmembrane segment M1 of the Na+, K+ -ATPase and its cytosolic extension. None of the alterations to charged and polar residues in the N-terminal part of M1 and its cytosolic extension had any major effect...... on the cation binding properties, thus rejecting the hypothesis that these residues are involved in cation selectivity. By contrast, specific residues in the middle part of M1, particularly Leu(99), were found critical to K+ interaction of the enzyme. Hence, mutation L99A reduced the affinity for K+ activation...... of E2P dephosphorylation 17-fold, and L99F reduced the equilibrium level of the K+-occluded intermediate [K2]E2 and increased the rate of K+ deocclusion 39-fold, i.e. more than seen for mutation E329Q of the cation-binding glutamate in M4. L99Q affected K+ interaction in yet another way...

  7. (nBuCp)2ZrCl2-catalyzed Ethylene-4M1P Copolymerization: Copolymer Backbone Structure, Melt Behavior, and Crystallization

    KAUST Repository

    Atiqullah, Muhammad

    2016-01-08

    The judicious design of methylaluminoxane (MAO) anions expands the scope for developing industrial metallocene catalysts. Therefore, the effects of MAO anion design on the backbone structure, melt behavior, and crystallization of ethylene−4-methyl-1-pentene (E−4M1P) copolymer were investigated. Ethylene was homopolymerized, as well as copolymerized with 4M1P, using (i) MAO anion A (unsupported [MAOCl2]−) premixed with dehydroxylated silica, (nBuCp)2ZrCl2, and Me2SiCl2; and (ii) MAO anion B (Si−O−Me2Si−[MAOCl2]−) supported with (nBuCp)2ZrCl2 on Me2SiCl2-functionalized silica. Unsupported Me2SiCl2, opposite to the supported analogue, acted as a co-chain transfer agent with 4M1P. The modeling of polyethylene melting and crystallization kinetics, including critical crystallite stability, produced insightful results. This study especially illustrates how branched polyethylene can be prepared from ethylene alone using particularly one metallocene-MAO ion pair, and how a compound, that functionalizes silica as well as terminates the chain, can synthesize ethylene−α-olefin copolymers with novel structures. Hence, it unfolds prospective future research niches in polyethyne systhesis. This article is protected by copyright. All rights reserved.

  8. The selective positive allosteric M1 muscarinic receptor modulator PQCA attenuates learning and memory deficits in the Tg2576 Alzheimer's disease mouse model.

    Science.gov (United States)

    Puri, Vanita; Wang, Xiaohai; Vardigan, Joshua D; Kuduk, Scott D; Uslaner, Jason M

    2015-01-01

    We have recently shown that the M1 muscarinic receptor positive allosteric modulator, PQCA, improves cognitive performance in rodents and non-human primates administered the muscarinic receptor antagonist scopolamine. The purpose of the present experiments was to characterize the effects of PQCA in a model more relevant to the disease pathology of Alzheimer's disease. Tg2576 transgenic mice that have elevated Aβ were tested in the novel object recognition task to characterize recognition memory as a function of age and treatment with the PQCA. The effects of PQCA were compared to the acetylcholinesterase inhibitor donepezil, the standard of care for Alzheimer's disease. In addition, the effect of co-administering PQCA and donepezil was evaluated. Aged Tg2576 mice demonstrated a deficit in recognition memory that was significantly attenuated by PQCA. The positive control donepezil also reversed the deficit. Furthermore, doses of PQCA and donepezil that were inactive on their own were found to improve recognition memory when given together. These studies suggest that M1 muscarinic receptor positive allosteric modulation can ameliorate memory deficits in disease relevant models of Alzheimer's disease. These data, combined with our previous findings demonstrating PQCA improves scopolamine-induced cognitive deficits in both rodents and non-human primates, suggest that M1 positive allosteric modulators have therapeutic potential for the treatment of Alzheimer's disease. Copyright © 2015 Elsevier B.V. All rights reserved.

  9. The stack: a new bacterial structure analyzed in the Antarctic bacterium Pseudomonas deceptionensis M1(T by transmission electron microscopy and tomography.

    Directory of Open Access Journals (Sweden)

    Lidia Delgado

    Full Text Available In recent years, improvements in transmission electron microscopy (TEM techniques and the use of tomography have provided a more accurate view of the complexity of the ultrastructure of prokaryotic cells. Cryoimmobilization of specimens by rapid cooling followed by freeze substitution (FS and sectioning, freeze fracture (FF and observation of replica, or cryoelectron microscopy of vitreous sections (CEMOVIS now allow visualization of biological samples close to their native state, enabling us to refine our knowledge of already known bacterial structures and to discover new ones. Application of these techniques to the new Antarctic cold-adapted bacterium Pseudomonasdeceptionensis M1(T has demonstrated the existence of a previously undescribed cytoplasmic structure that does not correspond to known bacterial inclusion bodies or membranous formations. This structure, which we term a "stack", was mainly visualized in slow growing cultures of P. deceptionensis M1(T and can be described as a set of stacked membranous discs usually arranged perpendicularly to the cell membrane, but not continuous with it, and found in variable number in different locations within the cell. Regardless of their position, stacks were mostly observed very close to DNA fibers. Stacks are not exclusive to P. deceptionensis M1(T and were also visualized in slow-growing cultures of other bacteria. This new structure deserves further study using cryoelectron tomography to refine its configuration and to establish whether its function could be related to chromosome dynamics.

  10. Glycyrrhizic Acid Promotes M1 Macrophage Polarization in Murine Bone Marrow-Derived Macrophages Associated with the Activation of JNK and NF-κB.

    Science.gov (United States)

    Mao, Yulong; Wang, Baikui; Xu, Xin; Du, Wei; Li, Weifen; Wang, Youming

    2015-01-01

    The roots and rhizomes of Glycyrrhiza species (licorice) have been widely used as natural sweeteners and herbal medicines. The aim of this study is to investigate the effect of glycyrrhizic acid (GA) from licorice on macrophage polarization. Both phenotypic and functional activities of murine bone marrow-derived macrophages (BMDMs) treated by GA were assessed. Our results showed that GA obviously increased the cell surface expression of CD80, CD86, and MHCII molecules. Meanwhile, GA upregulated the expression of CCR7 and the production of TNF-α, IL-12, IL-6, and NO (the markers of classically activated (M1) macrophages), whereas it downregulated the expression of MR, Ym1, and Arg1 (the markers of alternatively activated (M2) macrophage). The functional tests showed that GA dramatically enhanced the uptake of FITC-dextran and E. coli K88 by BMDMs and decreased the intracellular survival of E. coli K88 and S. typhimurium. Moreover, we demonstrated that JNK and NF-κB activation are required for GA-induced NO and M1-related cytokines production, while ERK1/2 pathway exhibits a regulatory effect via induction of IL-10. Together, these findings indicated that GA promoted polarization of M1 macrophages and enhanced its phagocytosis and bactericidal capacity. The results expanded our knowledge about the role of GA in macrophage polarization.

  11. Radiosensitivity of opium poppy (Papaver somniferum L.) and morphine content in the dry capsules of M1 as influenced by Cs137 gamma irradiation

    International Nuclear Information System (INIS)

    Popov, P.; Dimitrov, J.; Georgiev, S.; Deneva, T.

    1974-01-01

    Seeds of the poppy (Papaver somniferum L.) varieties P-360, S-188 and S-230 of ssp.turcicum, Novinka 198, Hatvani and Morfin mak of ssp.eurasiaticum were irradiated with Cs 137 gamma-ray doses of 5, 10, 15, 20, 25, 30, 35 and 40 krad at a dose-rate of 16 rad/min. The irradiated seeds were sown in the autumn of 1969 under field conditions and observed in M 1 . The following conclusions are made: (1) The lethal dose differs according to the individual poppy varieties. It is found to be above 40 krad for the varieties P-360 and S-188, 35 krad for Novinka 198 and 30 krad for S-230, Hatvani and Morfin mak. (2) In the M 1 generation the morphine content in the dry capsules shows a large variation depending on the variety and the irradiation dosis. (3) Irradiation-induced rise of the morphine content in the dry capsules of M 1 is higher in the varieties of ssp.turcicum than in the varieties of ssp.eurasiaticum. (M.Ts.)

  12. The nuclear export protein of H5N1 influenza A viruses recruits Matrix 1 (M1) protein to the viral ribonucleoprotein to mediate nuclear export.

    Science.gov (United States)

    Brunotte, Linda; Flies, Joe; Bolte, Hardin; Reuther, Peter; Vreede, Frank; Schwemmle, Martin

    2014-07-18

    In influenza A virus-infected cells, replication and transcription of the viral genome occurs in the nucleus. To be packaged into viral particles at the plasma membrane, encapsidated viral genomes must be exported from the nucleus. Intriguingly, the nuclear export protein (NEP) is involved in both processes. Although NEP stimulates viral RNA synthesis by binding to the viral polymerase, its function during nuclear export implicates interaction with viral ribonucleoprotein (vRNP)-associated M1. The observation that both interactions are mediated by the C-terminal moiety of NEP raised the question whether these two features of NEP are linked functionally. Here we provide evidence that the interaction between M1 and the vRNP depends on the NEP C terminus and its polymerase activity-enhancing property for the nuclear export of vRNPs. This suggests that these features of NEP are linked functionally. Furthermore, our data suggest that the N-terminal domain of NEP interferes with the stability of the vRNP-M1-NEP nuclear export complex, probably mediated by its highly flexible intramolecular interaction with the NEP C terminus. On the basis of our data, we propose a new model for the assembly of the nuclear export complex of Influenza A vRNPs. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  13. Effects of agonist efficacy on desensitization of phosphoinositide hydrolysis mediated by m1 and m3 muscarinic receptors expressed in Chinese hamster ovary cells

    International Nuclear Information System (INIS)

    Hu, J.; Wang, S.Z.; el-Fakahany, E.E.

    1991-01-01

    Muscarinic receptor agonist-induced desensitization of phosphoinositide (PI) hydrolysis and loss of receptors were studied in Chinese hamster ovary (CHO) cells transfected with the m1 and m3 muscarinic receptor genes. Long-term exposure to the full agonist carbamylcholine (CBC) resulted in a time-dependent attenuation of the maximal PI response and a decrease in agonist potency. This desensitization was accompanied by a parallel loss of maximal ligand binding without an alteration of the binding affinity. The time course of both receptor desensitization and down-regulation was similar in m1 and m3 CHO cells. The PI response to the partial agonist McN-A-343 (McN) in m1 cells was more sensitive to desensitization by CBC than the response to the latter agonist, and this desensitization was faster than receptor down-regulation. Desensitization of the PI response to McN was reflected as a decrease in the maximal response without a marked change in potency. McN induced slow desensitization of the PI response to CBC but a much faster desensitization of its own response. Our data provide evidence that although muscarinic agonist-induced desensitization of PI hydrolysis in CHO cells is due mainly to loss of receptors, there are other important factors which play a role in this process, e.g., receptor-effector uncoupling. The relative contribution of these different mechanisms depends on the efficacy of the agonists used for the receptor desensitization and activation steps

  14. The distribution of macrophages with a M1 or M2 phenotype in relation to prognosis and the molecular characteristics of colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Sofia Edin

    Full Text Available High macrophage infiltration has been correlated to improved survival in colorectal cancer (CRC. Tumor associated macrophages (TAMs play complex roles in tumorigenesis since they are believed to hold both tumor preventing (M1 macrophages and tumor promoting (M2 macrophages activities. Here we have applied an immunohistochemical approach to determine the degree of infiltrating macrophages with a M1 or M2 phenotype in clinical specimens of CRC in relation to prognosis, both in CRC in general but also in subgroups of CRC defined by microsatellite instability (MSI screening status and the CpG island methylator phenotype (CIMP. A total of 485 consecutive CRC specimens were stained for nitric oxide synthase 2 (NOS2 (also denoted iNOS as a marker for the M1 macrophage phenotype and the scavenger receptor CD163 as a marker for the M2 macrophage phenotype. The average infiltration of NOS2 and CD163 expressing macrophages along the invasive tumor front was semi-quantitatively evaluated using a four-graded scale. Two subtypes of macrophages, displaying M1 (NOS2(+ or M2 (CD163(+ phenotypes, were recognized. We observed a significant correlation between the amount of NOS2(+ and CD163(+ cells (P<0.0001. A strong inverse correlation to tumor stage was found for both NOS2 (P<0.0001 and CD163 (P<0.0001 infiltration. Furthermore, patients harbouring tumors highly infiltrated by NOS2(+ cells had a significantly better prognosis than those infiltrated by few NOS2(+ cells, and this was found to be independent of MSI screening status and CIMP status. No significant difference was found on cancer-specific survival in groups of CRC with different NOS2/CD163 ratios. In conclusion, an increased infiltration of macrophages with a M1 phenotype at the tumor front is accompanied by a concomitant increase in macrophages with a M2 phenotype, and in a stage dependent manner correlated to a better prognosis in patients with CRC.

  15. The Yersinia enterocolitica type three secretion chaperone SycO is integrated into the Yop regulatory network and binds to the Yop secretion protein YscM1

    Directory of Open Access Journals (Sweden)

    Heesemann Jürgen

    2007-07-01

    Full Text Available Abstract Background Pathogenic yersiniae (Y. pestis, Y. pseudotuberculosis, Y. enterocolitica share a virulence plasmid encoding a type three secretion system (T3SS. This T3SS comprises more than 40 constituents. Among these are the transport substrates called Yops (Yersinia outer proteins, the specific Yop chaperones (Sycs, and the Ysc (Yop secretion proteins which form the transport machinery. The effectors YopO and YopP are encoded on an operon together with SycO, the chaperone of YopO. The characterization of SycO is the focus of this study. Results We have established the large-scale production of recombinant SycO in its outright form. We confirm that Y. enterocolitica SycO forms homodimers which is typical for Syc chaperones. SycO overproduction in Y. enterocolitica decreases secretion of Yops into the culture supernatant suggesting a regulatory role of SycO in type III secretion. We demonstrate that in vitro SycO interacts with YscM1, a negative regulator of Yop expression in Y. enterocolitica. However, the SycO overproduction phenotype was not mediated by YscM1, YscM2, YopO or YopP as revealed by analysis of isogenic deletion mutants. Conclusion We present evidence that SycO is integrated into the regulatory network of the Yersinia T3SS. Our picture of the Yersinia T3SS interactome is supplemented by identification of the SycO/YscM1 interaction. Further, our results suggest that at least one additional interaction partner of SycO has to be identified.

  16. GM-CSF overexpression after influenza a virus infection prevents mortality and moderates M1-like airway monocyte/macrophage polarization.

    Science.gov (United States)

    Halstead, E Scott; Umstead, Todd M; Davies, Michael L; Kawasawa, Yuka Imamura; Silveyra, Patricia; Howyrlak, Judie; Yang, Linlin; Guo, Weichao; Hu, Sanmei; Hewage, Eranda Kurundu; Chroneos, Zissis C

    2018-01-05

    Influenza A viruses cause life-threatening pneumonia and lung injury in the lower respiratory tract. Application of high GM-CSF levels prior to infection has been shown to reduce morbidity and mortality from pathogenic influenza infection in mice, but the mechanisms of protection and treatment efficacy have not been established. Mice were infected intranasally with influenza A virus (PR8 strain). Supra-physiologic levels of GM-CSF were induced in the airways using the double transgenic GM-CSF (DTGM) or littermate control mice starting on 3 days post-infection (dpi). Assessment of respiratory mechanical parameters was performed using the flexiVent rodent ventilator. RNA sequence analysis was performed on FACS-sorted airway macrophage subsets at 8 dpi. Supra-physiologic levels of GM-CSF conferred a survival benefit, arrested the deterioration of lung mechanics, and reduced the abundance of protein exudates in bronchoalveolar (BAL) fluid to near baseline levels. Transcriptome analysis, and subsequent validation ELISA assays, revealed that excess GM-CSF re-directs macrophages from an "M1-like" to a more "M2-like" activation state as revealed by alterations in the ratios of CXCL9 and CCL17 in BAL fluid, respectively. Ingenuity pathway analysis predicted that GM-CSF surplus during IAV infection elicits expression of anti-inflammatory mediators and moderates M1 macrophage pro-inflammatory signaling by Type II interferon (IFN-γ). Our data indicate that application of high levels of GM-CSF in the lung after influenza A virus infection alters pathogenic "M1-like" macrophage inflammation. These results indicate a possible therapeutic strategy for respiratory virus-associated pneumonia and acute lung injury.

  17. IgE to recombinant allergens Api m 1, Ves v 1, and Ves v 5 distinguish double sensitization from crossreaction in venom allergy.

    Science.gov (United States)

    Müller, U; Schmid-Grendelmeier, P; Hausmann, O; Helbling, A

    2012-08-01

    Diagnostic tests in patients with Hymenoptera venom allergy are frequently positive to venoms of both honey bee and wasp (Vespula). Component-resolved analysis with recombinant species-specific major allergens (rSSMA) may help to distinguish true double sensitization from crossreactivity. Included were 121 patients with systemic allergic reactions to Hymenoptera stings, 76 with double positivity of serum-specific IgE (sIgE) to both venoms, 45 with single positivity to bee or wasp venom, and 32 controls without history of systemic reactions to Hymenoptera stings and no sIgE to whole venoms. In venom-allergic patients and controls, sIgE to rSSMA Api m 1 of bee venom and to Ves v 1 and Ves v 5 of wasp venom were tested by ImmunoCAP. Only 47% of 76 patients with double positivity to whole venoms reacted also to rSSMA of both species. Specificity of sIgE to the 3 rSSMA was very high, with no sIgE to rSSMA of the other species in single-positive venom-allergic patients and only one control with low sIgE to Ves v 1. All wasp-allergic single-positive patients had sIgE to Ves v 5 and/or Ves v 1, and 78.3% of single-positive bee venom-allergic patients had sIgE to Api m 1. Specificity of sIgE to rSSMA of both species is excellent. Sensitivity of sIgE to rSSMA was optimal for wasp venom. Sensitivity of bee venom Api m 1 could be increased by adding rSSMA of other important bee venom allergens. © 2012 John Wiley & Sons A/S.

  18. The prevalence of extended-spectrum beta-lactamases and CTX-M-1 producing Escherichia coli in urine samples collected at Tabriz city Hospitals

    Directory of Open Access Journals (Sweden)

    Soltan Dallal MM

    2011-08-01

    Full Text Available "nBackground: Numerous use of Beta Lactame in treatment of bacterial infections resulted in increments of drug resistance of such bacteria. One of difficulties in treatment of hospital infections is Extended Spectrum Beta Lactamase (ESBL among isolated clinical strains of E.coli. Since some of ESBL strains shows double reaction in drug sensitivity test at in vitro and in vivo condition, therefore it makes difficulties in selection of right treatment. In the last years, CTX-M enzymes have become the most prevalent ESBLs in worldwide. The prevalence of ESBL types largely remains unknown in many parts of the Iran. This study was made to find the prevalence of ESBL-producing E.coli and molecular detection of CTX-M-1 in Tabriz."n "nMethods: In the present study, 400 urine samples collected between November 2009 and April 2010, from Tabriz Hospitals were studied. Out of the 400 samples, 188 E.coli isolates were detected by standard biochemical tests. Susceptibility to antimicrobial agents was tested to 10 antibiotics by the disk agar diffusion (DAD method. ESBL production was screened by phenotypic test that included both separate and combined disk agar diffusion techniques. The screened isolates were investigated by PCR assay to detect CTX-M-1 gene."n "nResults: From the total 188 E.coli isolates, 82 (43.6% were shown to produce ESBLs by phenotypic test. During the PCR method on the 82 isolates, 69 (84.1% were confirmed as CTX-M-1 producing group."n "nConclusion: The present study showed that CTX-M-producing isolates were increasing among E.coli strains and indicated the need for adequate susceptibility tests in laboratories for choosing the appropriate antibiotics for treatment.

  19. [Inhibitory effects of pseudolaric acid B on inflammatory response and M1 phenotype polarization in RAW264.7 macrophages induced by lipopolysaccharide].

    Science.gov (United States)

    Li, Yuxiu; Li, Tan; Ji, Wenjie; Li, Xiao; Ma, Yongqiang; Zhao, Jihong; Zhou, Xin; Li, Yuming

    2016-05-01

    To investigate the effects of pseudolaric acid B (PLAB) on the inflammatory response and M1 phenotype polarization in RAW264.7 cells induced by lipopolysaccharide (LPS) and the related mechanisms. The inflammatory model in vitro was made using RAW264.7 cells stimulated by LPS, and then was treated with 0.5 μmol/L PLAB and 1 μmol/L GW9662, a peroxisome proliferators-activated receptor γ (PPARγ) antagonist. The cell cycle was tested by flow cytometry. The mRNA expressions of PPARγ and M1 phenotype markers interleukin 1β (IL-1β), tumor necrosis factor α (TNF-α) were measured by real-time PCR. The expression levels of signal molecules involved in nuclear factor-κB (NF-κB) signal pathway were detected by Western blotting. PLAB markedly decreased the expressions of IL-1β and TNF-α mRNAs induced by LPS and increased PPARγ mRNA level. Moreover, the expressions of NF-κB p65, pNF-κB p65, IKKα, IKKβ, pIKKα/β, IκBα and pIκBα decreased in PLAB-treated cells. Meanwhile, RAW264.7 cells were arrested in G0 and G2 phase after the treatment with PLAB. However, the effects of PLAB on RAW264.7 cells could be reversed by GW9662 obviously. PLAB could inhibit the inflammatory response and M1 phenotype polarization in RAW264.7 cells induced by LPS via modulating cell cycle and NF-κB/PPARγ signal pathway.

  20. Conditional cancer-specific mortality in T4, N1, or M1 prostate cancer: implications for long-term prognosis

    International Nuclear Information System (INIS)

    Muralidhar, Vinayak; Mahal, Brandon A.; Nguyen, Paul L.

    2015-01-01

    The risk of prostate cancer-specific mortality (PCSM) following a diagnosis of prostate cancer may improve after patients have survived a number of years after diagnosis. We sought to determine long-term conditional PCSM for patients with stage T4, N1, or M1 prostate cancer. We identified 66,817 patients diagnosed with stage IV (T4N0M0, N1M0, or M1) prostate cancer between 1973 and 2011 using the Surveillance, Epidemiology, and End Results (SEER) database. Conditional five-year PCSM was evaluated for each group of patients at 5, 10, and 15 years of survival according to the Fine & Gray model for competing risks after adjusting for tumor grade, age, income level, and marital status. Race-stratified analyses were also performed. There were 13,345 patients with T4 disease, 12,450 patients with N1 disease, and 41,022 patients with M1 disease. Median follow-up among survivors in the three groups was 123 months (range: 0–382 months), 61 months (range: 0–410 months), and 30 months (range: 0–370 months), respectively. Conditional PCSM improved in all three groups over time. Among patients with T4 disease, 5-year PCSM improved from 13.9 % at diagnosis to 11.2, 8.1, and 6.5 % conditioned on 5, 10, or 15 years of survival, respectively (p < 0.001 in all cases). In patients with N1 disease, 5-year PCSM increased within the first five years and decreased thereafter, from 18.9 % at diagnosis to 21.4 % (p < 0.001), 17.6 % (p = 0.055), and 13.8 % (p < 0.001), respectively. In patients with metastatic disease, 5-year PCSM improved from 57.2 % at diagnosis to 41.1, 28.8, and 20.8 %, respectively (p < 0.001). White race was associated with a greater increase in conditional survival compared to non-white race among those with T4 or N1 disease. While patients with T4, N1, or M1 prostate cancer are never “cured,” their odds of cancer-specific survival increase substantially after they have survived for 5 or more years. Physicians who take care of patients with prostate cancer

  1. Effects of muscarinic M1 and M4 acetylcholine receptor stimulation on extinction and reinstatement of cocaine seeking in male mice, independent of extinction learning

    DEFF Research Database (Denmark)

    Stoll, Kevin; Hart, Rachel; Lindsley, Craig W

    2017-01-01

    seeking, and whether this was mediated via memory consolidation. METHODS: Experimentally naïve C57BL/6J mice were allowed to acquire self-administration of intravenous cocaine (1 mg/kg/infusion) under a fixed-ratio 1 schedule of reinforcement. Then, saline was substituted for cocaine until responding...... sessions (7.5 and 6.4 sessions). Xanomeline-treated mice showed no cocaine-induced reinstatement. CONCLUSIONS: These findings show that M1/M4 receptor stimulation can decrease cocaine seeking in mice. The effect lasted beyond treatment duration and was not dependent upon extinction learning. This suggests...

  2. Nanocrystals of the quaternary thermoelectric materials: AgPb{sub m}SbTe{sub m+2}(m=1-18): Phase-segregated or solid solutions?

    Energy Technology Data Exchange (ETDEWEB)

    Arachchige, Indika U [Department of Chemistry, Northwestern University Evanston, IL (United States); Wu, Jinsong; Dravid, Vinayak P [Department of Materials Science and Engineering, Northwestern University Evanston, IL (United States); Kanatzidis, Mercouri G [Department of Chemistry, Northwestern University Evanston, IL (United States); Material Science Division, Argonne National Laboratory Argonne, IL (United States)

    2008-10-02

    Facile synthesis of a series of thermoelectrically relevant AgPb{sub m}SbTe{sub m+2}(m=1-18) nanoparticles is carried out by using a colloidal synthetic route. As-synthesized nanocrystals are spherical in geometry and adopt a cubic NaCl-type structure. These quaternary nanocrystals behave as solid solutions at room temperature and tend to phase separate into AgSbTe{sub 2} and PbTe upon annealing at moderately high temperature. (Abstract Copyright [2008], Wiley Periodicals, Inc.)

  3. Critical opalescence of the nuclear pion field: A possible evidence in the M1 (15.11 MeV) form factor of 12C

    International Nuclear Information System (INIS)

    Delorme, J.; Figureau, A.; Giraud, N.

    1980-01-01

    We have computed the nuclear pion field for the transition to the 15.11 MeV (1 + , T = 1) state of 12 C, evaluating the nuclear polarization with a large basis of nucleon- and isobar-hole excitations. The field shows an enhancement (or critical opalescence) in the momentum region beyond 1.5 msub(π) which leads to a substantial increase of the second maximum of the M1 form factor. Agreement with experiment can be obtained if the 12 C nucleus is much closer to the condensation threshold than currently expected. (orig.)

  4. Critical opalescence of the nuclear pion field: a possible evidence in the M1 (15.11 MeV) form factor of 12C

    International Nuclear Information System (INIS)

    Delorme, J.; Ericson, M.; Figureau, A.; Giraud, N.

    1979-07-01

    The nuclear pion field for the transition to the 15.11 MeV (1 + , T= 1) state of 12 C has been computed, evaluating the nuclear polarization with a large basis of nucleon- and isobar-hole excitations. The field shows an enhancement (or critical opalescence) in the momentum region beyond 1.5msub(π) which leads to a substantial increase of the second maximum of the M1 form factor. Agreement with experiment can be obtained if the 12 C nucleus is much closer to the pion condensation threshold than currently expected

  5. MicroR-146 blocks the activation of M1 macrophage by targeting signal transducer and activator of transcription 1 in hepatic schistosomiasis

    Directory of Open Access Journals (Sweden)

    Xing He

    2016-11-01

    Full Text Available Schistosomiasis is a chronic disease caused by the parasite of the Schistosoma genus and is characterized by egg-induced hepatic granulomas and fibrosis. Macrophages play a central role in schistosomiasis with several studies highlighting their differentiation into M2 cells involved in the survival of infected mice through limitation of immunopathology. However, little is known regarding the mechanisms of regulating macrophage differentiation. Here, we showed that the early stage of infection by Schistosoma japonicum induced expression of type 1 T-helper-cell (Th1 cytokine, interferon-γ (IFN-γ, leading to increase in M1 cells. However, the presence of liver-trapped eggs induced the expression of Th2 cytokines including interleukin-4 (IL-4, IL-10, and IL-13 that upregulated the transcription of miR-146b by activating signal transducer and activator of transcription 3/6 (STAT3/6 that bind to the promoter of the pre-miR-146b gene. We found that the miR-146a/b was significantly upregulated in macrophages during the progression of hepatic schistosomiasis. The elevated miR-146a/b inhibited the IFN-γ-induced differentiation of macrophages to M1 cells through targeting STAT1. Our data indicate the protective roles of miR-146a/b in hepatic schistosomiasis through regulating the differentiation of macrophages into M2 cells.

  6. Th1/M1 conversion to Th2/M2 responses in models of inflammation lacking cell death stimulates maturation of monocyte precursors to fibroblasts

    Directory of Open Access Journals (Sweden)

    JoAnn eTrial

    2013-09-01

    Full Text Available We have demonstrated that cardiac fibrosis arises from the differentiation of monocyte-derived fibroblasts. We present here evidence that this process requires sequential Th1 and Th2 induction promoting analogous M1 (classically activated and M2 (alternatively activated macrophage polarity. Our models are 1 mice subjected to daily repetitive ischemia reperfusion (I/R without infarction and 2 the in vitro transmigration of human mononuclear leukocytes through human cardiac microvascular endothelium. In the mouse heart, leukocytes entered after I/R in response to monocyte chemoattractant protein-1 (MCP-1 which is the major cytokine induced by this protocol. Monocytes within the heart then differentiated into fibroblasts making collagen while bearing the markers of M2 macrophages. T cells were seen in these hearts as well as in the human heart with cardiomyopathy. In the in vitro model, transmigration of the leukocytes was likewise induced by MCP-1 and some monocytes matured into fibroblasts bearing M2 markers. In this model, the MCP-1 stimulus induced a transient Th1 and M1 response that developed into a predominately Th2 and M2 response. An increase in the Th2 product IL-13 was present in both the human and the mouse models, consistent with its known role in fibrosis. In these simplified models, in which there is no cell death to stimulate an anti-inflammatory response, there is nonetheless a resolution of inflammation enabling a profibrotic environment. This induces the maturation of monocyte precursors into fibroblasts.

  7. Effect of metal properties of casts of steel-15Kh1M1FL on the crack resistance at 565 deg C

    International Nuclear Information System (INIS)

    Gladshtejn, V.I.; Sheshenev, M.F.

    1976-01-01

    Results are given of prolonged tests of the metal of industrial casts with various fluidity limits. It has been shown experimentally that a quite satisfactory crack resistance is characteristic of a metal with a fluidity limit in the range 30-50 kgf/mm 2 . Metallographic studies have been conducted. Upon variation of the structure and properties of the 15Kh1M1FL steel during operation, the rate of growth of small cracks (up to 2.0 mm) decreases almost by 3 orders of ten (from 1.4x10 -4 to 2.0x10 -7 mm/hour). Subsequent structural changes during prolonged operation (over 50000 hours) result in a gradual increase in the rate of crack growth. At the same time resistance towards appearance of the impermissible high rate of the crack growth, Ksub(10sup(-3)), diminishes monotonically with the operation time. The metal of industrial 15Kh1M1FL steel casts has good crack resistance (Ksub(10sup(-3)) =30-70 kgf/mmsup(3/2) and Vsub(ef) =) kgf/mm 2 ) and a satisfactory local plasticity (critical opening being no more than 0.20 mm for 10 3 hours)

  8. Charge Transfer Effects in Naturally Occurring van der Waals Heterostructures (PbSe )1.16(TiSe2 )m (m =1 , 2)

    Science.gov (United States)

    Yao, Q.; Shen, D. W.; Wen, C. H. P.; Hua, C. Q.; Zhang, L. Q.; Wang, N. Z.; Niu, X. H.; Chen, Q. Y.; Dudin, P.; Lu, Y. H.; Zheng, Y.; Chen, X. H.; Wan, X. G.; Feng, D. L.

    2018-03-01

    van der Waals heterostructures (VDWHs) exhibit rich properties and thus has potential for applications, and charge transfer between different layers in a heterostructure often dominates its properties and device performance. It is thus critical to reveal and understand the charge transfer effects in VDWHs, for which electronic structure measurements have proven to be effective. Using angle-resolved photoemission spectroscopy, we studied the electronic structures of (PbSe )1.16(TiSe2 )m (m =1 , 2), which are naturally occurring VDWHs, and discovered several striking charge transfer effects. When the thickness of the TiSe2 layers is halved from m =2 to m =1 , the amount of charge transferred increases unexpectedly by more than 250%. This is accompanied by a dramatic drop in the electron-phonon interaction strength far beyond the prediction by first-principles calculations and, consequently, superconductivity only exists in the m =2 compound with strong electron-phonon interaction, albeit with lower carrier density. Furthermore, we found that the amount of charge transferred in both compounds is nearly halved when warmed from below 10 K to room temperature, due to the different thermal expansion coefficients of the constituent layers of these misfit compounds. These unprecedentedly large charge transfer effects might widely exist in VDWHs composed of metal-semiconductor contacts; thus, our results provide important insights for further understanding and applications of VDWHs.

  9. The 2013 German-Russian BION-M1 Joint Flight Project: Skeletal Muscle and Neuromuscular Changes in Mice Housed for 30 Days in a Biosatellite on Orbit

    Science.gov (United States)

    Blottner, Dieter; Shenkman, Boris; Salanova, Michele

    Exposure to microgravity results in various structural, biochemical and molecular changes of the skeletal neuromuscular system. The BION Joint Flight Proposal between the Charité Berlin Center of Space Medicine (www.zwmb.de) in Berlin, and the Institute of Biomedical Problem (IMBP) in Moscow, provided an exciting opportunity for a more detailed analysis of neuromuscular changes in mice (C57/bl6) exposed to real microgravity housed for 30 days in a BION M1 biosatellite on orbit. The mice from the BION flight group (n=5) were compared to three different on-ground control groups (Flight control, BION-ground and Vivarium, each n=5 mice). We started to analyse various skeletal muscles from the hind limbs or trunk. Apart from routine structural and biochemical analysis (fiber size and type distribution, slow/fastMyHC) we test the hypothesis for the presence of a microgravity-induced sarcolemma-cytosolic protein shift of nitric oxide synthase (NOS) and partial loss in neuromuscular synapse scaffold protein (Homer) immunoexpression known to be prone to disuse in mice or humans (hind limb unloading, bed rest) as previously shown (Sandonà D et al., PLoS One, 2012, Salanova M et al., FASEB J, 2011). National Sponsors: Federal Ministry of Economics and Technology (BMWi) via the German AeroSpace Board, DLR e.V., Bonn-Oberkassel, Germany (#50WB1121); Contract RAS-IMBP/Charité Berlin # Bion-M1/2013

  10. The effect of gamma radiation on seeds and plants of different genotypes of Pisum arvense (L.s.s.) in the M1 generation

    International Nuclear Information System (INIS)

    Jaranowski, J.K.

    1976-01-01

    This paper presents results concerning radiosensitivity of seeds of field pea (Pisum arvense L.s.s.) and the analysis of the M 1 generation plants. For the present studies seeds of seven established (homozygous) lines, derived from crosses between forms and varieties of different agriculturo-geographical regions of Europe, were chosen. These lines differed by a number of morphological and physiological characters. The seeds were exposed to gamma radiation at the doses of: 1 kR/5 hrs, 6 kR/25 hrs, 12 kR/100 hrs, 25 kR/100 hrs and 50 kR/100 hrs. While analysing after the irradiation such phenomena as germinating and emergence capacity, survival of plants after emergence, morphological changes of plants, fertility and chromosome aberrations, it has been found that the radiosensitivity of various lines is convincingly different. Attempts to find certain correlations between the presence of definite genes in the lines, the size and structure of chromosomes, the structure of seeds (size, shape, coloration) gave negative results. Results obtained by the author and those of the literature indicate that radiosensitivity of pea seeds and characters of the M 1 generation plants are very complicated phenomena and it is difficult to establish definite regularities. (author)

  11. Models for financial crisis detection in Indonesia based on M1, M2 per foreign exchange reverse, and M2 multiplier indicators

    Science.gov (United States)

    Sugiyanto; Zukhronah, Etik; Pratiwi, Esteti Sophia

    2017-12-01

    Indonesia has been hit by financial crisis in the middle of 1997. The financial crisis that has occurred gives a severe impact to the economy of Indonesia resulting the needs for a detection system of financial crisis. Crisis can be detected based on several indicators such as M1, M2 per foreign exchange reserves, and M2 multiplier. These three indicators can affect the exchange rate stability and may further affect the financial stability so that it can be one of the causes of the financial crisis. This research aims to determine the appropriate model that can detect the financial crisis in Indonesia. Markov switching is an alternative model that can be approach and used often for detecting financial crisis. We can determine the combination of volatility and Markov switching model with AR and volatility model are determined first. The results of this research are that M1 can be modelled by SWARCH (3, 1) while M2 per foreign research exchange reserves and M2 multiplier can be modelled by SWARCH(3,2).

  12. Calculation of parity violating effects in the 62P/sub 1/2/-72P/sub 1/2/ forbidden M1 transition in thallium

    International Nuclear Information System (INIS)

    Neuffer, D.B.

    1977-05-01

    Calculations are presented of the E1 amplitude expected in forbidden M1 transitions of Tl and Cs if parity is violated in the neutral weak e-N interaction, as proposed in a number of gauge models, including that of Weinberg and Salam. Valence electron wave functions are generated as numerical solutions to the Dirac equation in a modified Tietz central potential. These wave functions are used to calculate allowed E1 transition rates, hfs splittings, and Stark E1 transition ampitudes. These results are compared with experiment and the agreement is generally good. The relativistic Tl 6 2 P/sub 1/2/-7 2 P/sub 1/2/ M1 transition amplitude M is also calculated, and corrections due to interconfiguration interaction, Breit interaction, and hfs mixing are included. The parity violating E1 amplitude E/sub PV/ is calculated and a value for the circular dichroism in the Weinberg model delta = -2.6 x 10 -3 is obtained. Parity violating effects in other Tl transitions are discussed. Contributions to the M1 amplitude for the forbidden Cs 6 2 S/sub 1/2/-7 2 S/sub 1/2/ and 6 2 S/sub 1/2/-8 2 S/sub 1/2/ transitions and to the Cs 6 2 S/sub 1/2/ g-factor anomaly from relativistic effects, Breit interaction, interconfiguration interaction, and hfs mixing are calculated, and it is found that this current theoretical description is not entirely adequate. The parity violating E1 amplitude E/sub PV/ for the 6S/sub 1/2/-7 2 S/sub 1/2/ and 6S/sub 1/2/-8 2 S/sub 1/2/ transitions is evaluated. With a measured value M/sub expt/ and the Weinberg value Q/sub W/ = -99, a circular dichroism delta = 1.64 x 10 -4 for the 6 2 S/sub 1/2/-7 2 S/sub 1/2/ transition is found

  13. Differential regulation by agonist and phorbol ester of cloned m1 and m2 muscarinic acetylcholine receptors in mouse Y1 adrenal cells and in Y1 cells deficient in cAMP-dependent protein kinase

    International Nuclear Information System (INIS)

    Scherer, N.M.; Nathanson, N.M.

    1990-01-01

    Cloned muscarinic acetylcholine m1 and m2 receptors were expressed in stably transfected mouse Y1 adrenal cells and in a variant Y1 line, Kin-8, which is deficient in cAMP-dependent protein kinase activity (PKA - ). m1 and m2 receptors were rapidly internalized following exposure of transfected PKA + or PKA - cells to the muscarinic agonist carbachol. Thus, agonist-dependent internalization of m1 and m2 did not require PKA activity. A differential effect of PKA on regulation by agonist of the m2 receptor, but not the m1 receptor, was unmasked in PKA - cells. These data indicate that the basal activity of PKA may modulate the agonist-dependent internalization of the m2 receptor, but not the m1 receptor. The internalization of the m1 and m2 receptors in both PKA + and PKA - cells was accompanied by desensitization of functional responses. Exposure of PKA + cells to 10 -7 M phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, resulted in a 30 ± 9% decrease in the number of m1 receptors on the cell surface. The m2 receptor was not internalized following treatment of either PKA + or PKA - cells with PMA. Thus, the m1 and m2 receptors show differential sensitivity to internalization by PMA. Agonist-dependent internalization of the m1 receptor appeared to be independent of activation of PKC because (1) agonist-dependent internalization of m1 was not attenuated in PKA - cells, (2) the rate and extent of internalization of m1 in cells exposed to PMA were less than those in cells exposed to agonist, and (3) treatment of cells with concanavalin A selectivity blocked internalization of m1 in cells exposed to PMA, but not to agonist. The effects of agonist and PMA on receptor internalization were not additive. Exposure of PKA + or PKA - cells to PMA reduced the magnitude of pilocarpine-stimulated PI hydrolysis by about 25%

  14. Fission gas release and swelling in the fuel pins M1-3 and F9-3: Risoe Fission Gas Project

    Energy Technology Data Exchange (ETDEWEB)

    Walker, C T; Ray, I L.F.; Coquerelle, M; Blank, H

    1982-01-01

    This report presents results for the microscopic swelling local swelling and local gas release in the pin sections M1-3-11 and F9-3-44. The local gas release was derived from the concentration of retained xenon which was measured with the electron microprobe. In addition to xenon, the radial distributions of caesium and neodymium were also determined by EMPA. Caesium is assumed to contribute to microscopic swelling because it results mainly from the decay of /sup 133/Xe, /sup 135/Xe and /sup 137/Xe and, therefore, is trapped together with xenon in bubbles and pores. Neodymium, on the other hand, is soluble in UO/sub 2/ and does not migrate under the influence of the temperature gradients that exist during irradiation. Therefore, the radial distribution of this fission product is an indelible imprint of the burn-up from which the average flux depression can be deduced. 1 ref., 15 figs., 3 tabs.

  15. Analysis of aflatoxin M1 in milk and yogurt and AFM1 reduction by lactic acid bacteria used in Lebanese industry

    International Nuclear Information System (INIS)

    El Khoury, A.; Yaghi, J.; Atoui, A.

    2011-01-01

    In this study a screening survey was undertaken to determine the presence and levels of aflatoxin M1 (AFM1) in locally produced dairy products. For this purpose, a total of 138 dairy samples (milk and yogurt) were analyzed to quantify AFM1 levels in these products. Results obtained showed that AFM1 was found in 40.62% and 32.81% of milk and yogurt samples respectively. The range of contamination levels varied between lower and higher than European regulation limit. Lactic acid bacteria (Lactobacillus bulgaricus and Streptococcus thermophilus) used in the Lebanese traditional industry were screened for their ability to reduce the level of AFM1. Due to the lack in data on the natural occurrence of AFM1 in Lebanese dairy products, the aim of this work was to report some information and to state these products according to EC regulations. (author)

  16. The influenza fingerprints: NS1 and M1 proteins contribute to specific host cell ultrastructure signatures upon infection by different influenza A viruses

    Energy Technology Data Exchange (ETDEWEB)

    Terrier, Olivier; Moules, Vincent; Carron, Coralie; Cartet, Gaeelle [Equipe VirCell, Laboratoire de Virologie et Pathologie Humaine, VirPath EMR 4610, Universite de Lyon, Universite Claude Bernard Lyon 1, Hospices Civils de Lyon, Faculte de medecine RTH Laennec, rue Guillaume Paradin, F-69008 Lyon (France); Frobert, Emilie [Laboratoire de Virologie, Centre de Biologie et de Pathologie Est, Hospices Civils de Lyon, 59 boulevard Pinel, F-69677 Bron Cedex, Lyon (France); Yver, Matthieu; Traversier, Aurelien [Equipe VirCell, Laboratoire de Virologie et Pathologie Humaine, VirPath EMR 4610, Universite de Lyon, Universite Claude Bernard Lyon 1, Hospices Civils de Lyon, Faculte de medecine RTH Laennec, rue Guillaume Paradin, F-69008 Lyon (France); Wolff, Thorsten [Division of Influenza/Respiratory Viruses, Robert Koch Institute, Nordufer 20, D-13353 Berlin (Germany); Riteau, Beatrice [Laboratoire de Virologie et Pathologie Humaine, VirPath EMR 4610, Universite de Lyon, Universite Claude Bernard Lyon 1, Hospices Civils de Lyon, Faculte de medecine RTH Laennec, rue Guillaume Paradin, F-69008 Lyon (France); Naffakh, Nadia [Institut Pasteur, Unite de Genetique Moleculaire des Virus Respiratoires, URA CNRS 3015, EA302 Universite Paris Diderot, Paris (France); and others

    2012-10-10

    Influenza A are nuclear replicating viruses which hijack host machineries in order to achieve optimal infection. Numerous functional virus-host interactions have now been characterized, but little information has been gathered concerning their link to the virally induced remodeling of the host cellular architecture. In this study, we infected cells with several human and avian influenza viruses and we have analyzed their ultrastructural modifications by using electron and confocal microscopy. We discovered that infections lead to a major and systematic disruption of nucleoli and the formation of a large number of diverse viral structures showing specificity that depended on the subtype origin and genomic composition of viruses. We identified NS1 and M1 proteins as the main actors in the remodeling of the host ultra-structure and our results suggest that each influenza A virus strain could be associated with a specific cellular fingerprint, possibly correlated to the functional properties of their viral components.

  17. Search for 14.4 keV solar axions emitted in the M1-transition of $^{57}$Fe nuclei with CAST

    CERN Document Server

    Andriamonje, S; Autiero, D; Barth, K; Belov, A; Beltrán, B; Bräuninger, H; Carmona, J M; Cebrián, S; Collar, J I; Dafni, T; Davenport, M; Di Lella, L; Eleftheriadis, C; Englhauser, J; Fanourakis, G K; Ferrer-Ribas, E; Fischer, H; Franz, J; Friedrich, P; Geralis, T; Giomataris, Yu; Gninenko, S; Gómez, H; Hasinoff, M; Heinsius, F H; Hoffmann, D H H; Irastorza, I G; Jacoby, J; Jakovčić, K; Kang, D; Königsmann, K C; Kotthaus, R; Krčmar, M; Kousouris, K; Kuster, M; Lakić, B; Lasseur, C; Liolios, A; Ljubičić, A; Lutz, G; Luzón, G; Miller, D; Morales, J; Ortiz, A; Papaevangelou, T; Placci, A; Raffelt, G; Riege, H; Rodríguez, A; Ruz, J; Savvidis, I; Semertzidis, Y; Serpico, P; Stewart, L; Vieira, J; Villar, J; Vogel, J; Walckiers, L; Zioutas, K

    2009-01-01

    We have searched for 14.4 keV solar axions or more general axion-like particles (ALPs), that may be emitted in the M1 nuclear transition of 57Fe, by using the axion-to-photon conversion in the CERN Axion Solar Telescope (CAST) with evacuated magnet bores (Phase I). From the absence of excess of the monoenergetic X-rays when the magnet was pointing to the Sun, we set model-independent constraints on the coupling constants of pseudoscalar particles that couple to two photons and to a nucleon g_{a\\gamma} |-1.19 g_{aN}^{0}+g_{aN}^{3}|<1.36\\times 10^{-16} GeV^{-1} for m_{a}<0.03 eV at the 95% confidence level.

  18. The influenza fingerprints: NS1 and M1 proteins contribute to specific host cell ultrastructure signatures upon infection by different influenza A viruses

    International Nuclear Information System (INIS)

    Terrier, Olivier; Moules, Vincent; Carron, Coralie; Cartet, Gaëlle; Frobert, Emilie; Yver, Matthieu; Traversier, Aurelien; Wolff, Thorsten; Riteau, Beatrice; Naffakh, Nadia

    2012-01-01

    Influenza A are nuclear replicating viruses which hijack host machineries in order to achieve optimal infection. Numerous functional virus–host interactions have now been characterized, but little information has been gathered concerning their link to the virally induced remodeling of the host cellular architecture. In this study, we infected cells with several human and avian influenza viruses and we have analyzed their ultrastructural modifications by using electron and confocal microscopy. We discovered that infections lead to a major and systematic disruption of nucleoli and the formation of a large number of diverse viral structures showing specificity that depended on the subtype origin and genomic composition of viruses. We identified NS1 and M1 proteins as the main actors in the remodeling of the host ultra-structure and our results suggest that each influenza A virus strain could be associated with a specific cellular fingerprint, possibly correlated to the functional properties of their viral components.

  19. Role of household exposure, dietary habits and glutathione S-Transferases M1, T1 polymorphisms in susceptibility to lung cancer among women in Mizoram India.

    Science.gov (United States)

    Phukan, Rup Kumar; Saikia, Bhaskar Jyoti; Borah, Prasanta Kumar; Zomawia, Eric; Sekhon, Gaganpreet Singh; Mahanta, Jagadish

    2014-01-01

    A case-control study was conducted to evaluate the effect of household exposure, dietary habits, smoking and Glutathione S-Transferases M1, T1 polymorphisms on lung cancer among women in Mizoram, India. We selected 230 newly diagnosed primary lung cases and 460 controls from women in Mizoram. Multivariate logistic regression analysis was performed to estimate adjusted odds ratio (OR). Exposure of cooking oil fumes (pkitchen inside living room (p=0.001), improper ventilated house (p=0.003), roasting of soda in kitchen (p=0.001), current smokers of tobacco (p=0.043), intake of smoked fish (p=0.006), smoked meat (p=0.001), Soda (poil emission and wood smoke, intake of smoked meat, smoked fish and soda (an alkali preparation used as food additives in Mizoram) and tobacco consumption for increase risk of lung cancer among Women in Mizoram.

  20. Heat affected zone structure in welded joints of 15Kh1M1FL, 25Kh2NMFA and 20KhN2MFA steels

    International Nuclear Information System (INIS)

    Levenberg, N.E.; German, S.I.; Fomina, O.P.; Netesa, E.M.; Tsaryuk, A.K.; Kornienko, T.A.

    1983-01-01

    Heat affected zone (HAZ) structure of thick-walled, nature joints of 15Kh1M1FL steel for block structure of power reactors and 25Kh2NMFA and 20KhN2MFA steels for rotors - is investigated. Multi-layer arc welding is performed under conditions being created for standard components of turbines. Thermokinetics diagrams of austenite decomposition are built, phase composition and character of the structure forming at HAZ in the process of welding with preheating are studied. It is shown that at HAZ in joints of the steels under consideration in the process of welding with preheating is formed a structure of a grained bainite which is uniform in its structure and phase composition. Small volumes of round and elongated forms consisting of martensite and residual austenite are distributed in α-solid solution of the bainite. The bainite of the HAZ in welded joints possesses high hardness and great stability in the process of tempering

  1. Emergence of extended spectrum beta-lactamases-producing strains belonging to cefotaxime-M-1 class from intensive care units patients and environmental surfaces in Pakistan

    Directory of Open Access Journals (Sweden)

    Aqsa Ashraf Bukhari

    2016-11-01

    Full Text Available Aim: The emergence of multidrug-resistant (MDR bacteria is the most dangerous threat for the treatment of infectious diseases. The aim of this study was to detect and characterize extended spectrum beta-lactamases (ESBLs and carbapenemase-producing Klebsiella pneumoniae and Escherichia coli among patients and environment of intensive care units (ICUs of three tertiary care hospitals in Pakistan. Materials and Methods: A total of 82 samples from ICU’s patients and inanimate environment (injection trays, wash basins, door handles, hand swabs of professionals, and ICU fridges were screened for ESBL by culturing on CHROMagar-ESBL. ESBL and carbapenemases production were confirmed by double disc synergy test and modified Hodge’s test, respectively. Polymerase chain reaction was used to detect ESBL encoding genes bla cefotaxime (CTX-M, blaCTX-M-1, blaCTX-M-2, blaCTX-M-9, blaTEM, blaSHV and carbapenemase genes blaKPC, bla New Delhi metallo-beta-lactamase-1, blaOXA-48 and blaVIM. Results: Overall, ESBL production was found high 30/82 (36.5% among isolates of which 15.8% K. pneumoniae and 20.7% E. coli were identified. All the K. pneumoniae and majority of E. coli isolates were MDR, i.e., resistance to three or more antimicrobial categories. Molecular characterization showed the blaCTX-M-1 as the predominant genotype found in 17/21 (80% of the isolates. None of the strains was found positive for carbapenemase-encoding genes. Conclusion: In conclusion, this study demonstrates the emergence of MDR ESBL producing strains among ICU patients and hospital environment, posing a serious threat for the control of nosocomial infections.

  2. Genome-wide discovery of novel M1T1 group A streptococcal determinants important for fitness and virulence during soft-tissue infection.

    Directory of Open Access Journals (Sweden)

    Yoann Le Breton

    2017-08-01

    Full Text Available The Group A Streptococcus remains a significant human pathogen causing a wide array of disease ranging from self-limiting to life-threatening invasive infections. Epithelium (skin or throat colonization with progression to the subepithelial tissues is the common step in all GAS infections. Here, we used transposon-sequencing (Tn-seq to define the GAS 5448 genetic requirements for in vivo fitness in subepithelial tissue. A near-saturation transposon library of the M1T1 GAS 5448 strain was injected subcutaneously into mice, producing suppurative inflammation at 24 h that progressed to prominent abscesses with tissue necrosis at 48 h. The library composition was monitored en masse by Tn-seq and ratios of mutant abundance comparing the output (12, 24 and 48 h versus input (T0 mutant pools were calculated for each gene. We identified a total of 273 subcutaneous fitness (scf genes with 147 genes (55 of unknown function critical for the M1T1 GAS 5448 fitness in vivo; and 126 genes (53 of unknown function potentially linked to in vivo fitness advantage. Selected scf genes were validated in competitive subcutaneous infection with parental 5448. Two uncharacterized genes, scfA and scfB, encoding putative membrane-associated proteins and conserved among Gram-positive pathogens, were further characterized. Defined scfAB mutants in GAS were outcompeted by wild type 5448 in vivo, attenuated for lesion formation in the soft tissue infection model and dissemination to the bloodstream. We hypothesize that scfAB play an integral role in enhancing adaptation and fitness of GAS during localized skin infection, and potentially in propagation to other deeper host environments.

  3. Structural comparison of tRNA m1A58 methyltransferases revealed different molecular strategies to maintain their oligomeric architecture under extreme conditions

    Directory of Open Access Journals (Sweden)

    Guelorget Amandine

    2011-12-01

    Full Text Available Abstract Background tRNA m1A58 methyltransferases (TrmI catalyze the transfer of a methyl group from S-adenosyl-L-methionine to nitrogen 1 of adenine 58 in the T-loop of tRNAs from all three domains of life. The m1A58 modification has been shown to be essential for cell growth in yeast and for adaptation to high temperatures in thermophilic organisms. These enzymes were shown to be active as tetramers. The crystal structures of five TrmIs from hyperthermophilic archaea and thermophilic or mesophilic bacteria have previously been determined, the optimal growth temperature of these organisms ranging from 37°C to 100°C. All TrmIs are assembled as tetramers formed by dimers of tightly assembled dimers. Results In this study, we present a comparative structural analysis of these TrmIs, which highlights factors that allow them to function over a large range of temperature. The monomers of the five enzymes are structurally highly similar, but the inter-monomer contacts differ strongly. Our analysis shows that bacterial enzymes from thermophilic organisms display additional intermolecular ionic interactions across the dimer interfaces, whereas hyperthermophilic enzymes present additional hydrophobic contacts. Moreover, as an alternative to two bidentate ionic interactions that stabilize the tetrameric interface in all other TrmI proteins, the tetramer of the archaeal P. abyssi enzyme is strengthened by four intersubunit disulfide bridges. Conclusions The availability of crystal structures of TrmIs from mesophilic, thermophilic or hyperthermophilic organisms allows a detailed analysis of the architecture of this protein family. Our structural comparisons provide insight into the different molecular strategies used to achieve the tetrameric organization in order to maintain the enzyme activity under extreme conditions.

  4. Hydrogen peroxide modulates energy metabolism and oxidative stress in cultures of permanent human Müller cells MIO-M1.

    Science.gov (United States)

    Peters, Sven; Griebsch, Max; Klemm, Matthias; Haueisen, Jens; Hammer, Martin

    2017-09-01

    In this study the influence of hydrogen peroxide (H 2 O 2 ) on the redox state, NADH protein binding, and mitochondrial membrane potential in Müller cells is investigated. Cultures of permanent human Müller cells MIO-M1 were exposed to H 2 O 2 in 75 µM and 150 µM concentration for two hours. Fluorescence emission spectra and lifetimes were measured by two-photon microscopy (excitation wavelength: 740 nm) at the mitochondria which were identified in the microscopic images by their fluorescence properties (spectra and intensity). Two hours of H 2 O 2 exposure did not impair viability of MIO-M1 cells in culture. Whereas the ratio of flavine- to NADH fluorescence intensity did not change under either H 2 O 2 concentration, the mean lifetime was significantly different between controls, not exposed to H 2 O 2 , and the 150 µM H 2 O 2 exposure (972 ± 63 ps vs. 1152 ± 64 ps, p = 0.014). One hour after cessation of the H 2 O 2 exposure, the value retuned to that of the control (983 ± 36 ps). A hyperpolarization of the mitochondrial membrane under 150 µM H 2 O 2 was found. These findings suggest a shift form free to protein-bound NADH in mitochondria as well as a hyperpolarization of their inner membrane which could be related to an impairment of Müller cell function despite their preserved viability. Exposure of human Müller cells to hydrogen peroxide for two hours results in a reversible change of protein binding of mitochondrial NADH upon unchanged redox ratio. The mitochondrial membrane potential is increased during exposure. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Genome-wide discovery of novel M1T1 group A streptococcal determinants important for fitness and virulence during soft-tissue infection.

    Science.gov (United States)

    Le Breton, Yoann; Belew, Ashton T; Freiberg, Jeffrey A; Sundar, Ganesh S; Islam, Emrul; Lieberman, Joshua; Shirtliff, Mark E; Tettelin, Hervé; El-Sayed, Najib M; McIver, Kevin S

    2017-08-01

    The Group A Streptococcus remains a significant human pathogen causing a wide array of disease ranging from self-limiting to life-threatening invasive infections. Epithelium (skin or throat) colonization with progression to the subepithelial tissues is the common step in all GAS infections. Here, we used transposon-sequencing (Tn-seq) to define the GAS 5448 genetic requirements for in vivo fitness in subepithelial tissue. A near-saturation transposon library of the M1T1 GAS 5448 strain was injected subcutaneously into mice, producing suppurative inflammation at 24 h that progressed to prominent abscesses with tissue necrosis at 48 h. The library composition was monitored en masse by Tn-seq and ratios of mutant abundance comparing the output (12, 24 and 48 h) versus input (T0) mutant pools were calculated for each gene. We identified a total of 273 subcutaneous fitness (scf) genes with 147 genes (55 of unknown function) critical for the M1T1 GAS 5448 fitness in vivo; and 126 genes (53 of unknown function) potentially linked to in vivo fitness advantage. Selected scf genes were validated in competitive subcutaneous infection with parental 5448. Two uncharacterized genes, scfA and scfB, encoding putative membrane-associated proteins and conserved among Gram-positive pathogens, were further characterized. Defined scfAB mutants in GAS were outcompeted by wild type 5448 in vivo, attenuated for lesion formation in the soft tissue infection model and dissemination to the bloodstream. We hypothesize that scfAB play an integral role in enhancing adaptation and fitness of GAS during localized skin infection, and potentially in propagation to other deeper host environments.

  6. Group A Streptococcus M1T1 Intracellular Infection of Primary Tonsil Epithelial Cells Dampens Levels of Secreted IL-8 Through the Action of SpyCEP

    Directory of Open Access Journals (Sweden)

    Amelia T. Soderholm

    2018-05-01

    Full Text Available Streptococcus pyogenes (Group A Streptococcus; GAS commonly causes pharyngitis in children and adults, with severe invasive disease and immune sequelae being an infrequent consequence. The ability of GAS to invade the host and establish infection likely involves subversion of host immune defenses. However, the signaling pathways and innate immune responses of epithelial cells to GAS are not well-understood. In this study, we utilized RNAseq to characterize the inflammatory responses of primary human tonsil epithelial (TEpi cells to infection with the laboratory-adapted M6 strain JRS4 and the M1T1 clinical isolate 5448. Both strains induced the expression of genes encoding a wide range of inflammatory mediators, including IL-8. Pathway analysis revealed differentially expressed genes between mock and JRS4- or 5448-infected TEpi cells were enriched in transcription factor networks that regulate IL-8 expression, such as AP-1, ATF-2, and NFAT. While JRS4 infection resulted in high levels of secreted IL-8, 5448 infection did not, suggesting that 5448 may post-transcriptionally dampen IL-8 production. Infection with 5448ΔcepA, an isogenic mutant lacking the IL-8 protease SpyCEP, resulted in IL-8 secretion levels comparable to JRS4 infection. Complementation of 5448ΔcepA and JRS4 with a plasmid encoding 5448-derived SpyCEP significantly reduced IL-8 secretion by TEpi cells. Our results suggest that intracellular infection with the pathogenic GAS M1T1 clone induces a strong pro-inflammatory response in primary tonsil epithelial cells, but modulates this host response by selectively degrading the neutrophil-recruiting chemokine IL-8 to benefit infection.

  7. How does a surgeon's brain buzz? An EEG coherence study on the interaction between humans and robot.

    Science.gov (United States)

    Bocci, Tommaso; Moretto, Carlo; Tognazzi, Silvia; Briscese, Lucia; Naraci, Megi; Leocani, Letizia; Mosca, Franco; Ferrari, Mauro; Sartucci, Ferdinando

    2013-04-22

    In humans, both primary and non-primary motor areas are involved in the control of voluntary movements. However, the dynamics of functional coupling among different motor areas have not been fully clarified yet. There is to date no research looking to the functional dynamics in the brain of surgeons working in laparoscopy compared with those trained and working in robotic surgery. We enrolled 16 right-handed trained surgeons and assessed changes in intra- and inter-hemispheric EEG coherence with a 32-channels device during the same motor task with either a robotic or a laparoscopic approach. Estimates of auto and coherence spectra were calculated by a fast Fourier transform algorithm implemented on Matlab 5.3. We found increase of coherence in surgeons performing laparoscopy, especially in theta and lower alpha activity, in all experimental conditions (M1 vs. SMA, S1 vs. SMA, S1 vs. pre-SMA and M1 vs. S1; p right vs. left M1, right vs. left S1, right pre-SMA vs. left M1, left pre-SMA vs. right M1; p brain and robotic devices.

  8. Comparison of cytogenetic effects in bone marrow of mice after the flight on the biosatellite "BION-M1" and the ground-based radiobiological experiment