WorldWideScience

Sample records for m1 pre-sma pmc

  1. Dissociable roles of preSMA in motor sequence chunking and hand switching-a TMS study.

    Science.gov (United States)

    Muessgens, Diana; Thirugnanasambandam, Nivethida; Shitara, Hitoshi; Popa, Traian; Hallett, Mark

    2016-12-01

    Motor chunking, the grouping of individual movements into larger units, is crucial for sequential motor performance. The presupplementary motor area (preSMA) is involved in chunking and other related processes such as task switching, response selection, and response inhibition that are crucial for organizing sequential movements. However, previous studies have not systematically differentiated the role of preSMA in motor chunking and hand switching, thus leaving its relative contribution to each of these processes unclear. The aim of this study is to demonstrate the differential role of preSMA in motor chunking and hand switching. We designed motor sequences in which different kinds of hand switches (switching toward the right or left hand or continuing with the right hand) were counterbalanced across between- and within-chunk sequence points. Eighteen healthy, right-handed participants practiced four short subsequences (chunks) of key presses. In a subsequent task, these chunks had to be concatenated into one long sequence. We applied double-pulse transcranial magnetic stimulation (TMS) over left preSMA or left M1 areas at sequence initiation, between chunks, or within chunks. TMS over the left preSMA significantly slowed the next response when stimulation was given between chunks, but only if a hand switch toward the contralateral (right) hand was required. PreSMA stimulation within chunks did not interfere with responses. TMS over the left M1 area delayed responses with the contralateral hand, both within and between chunks. Both preSMA and M1 stimulation decreased response times at sequence initiation. These results suggest that left preSMA is not necessary for chunking per se, but rather for organizing complex movements that require chunking and hand switching simultaneously.

  2. Anodal transcranial direct current stimulation (tDCS) over supplementary motor area (SMA) but not pre-SMA promotes short-term visuomotor learning.

    Science.gov (United States)

    Vollmann, Henning; Conde, Virginia; Sewerin, Sebastian; Taubert, Marco; Sehm, Bernhard; Witte, Otto W; Villringer, Arno; Ragert, Patrick

    2013-03-01

    Non-invasive brain stimulation such as transcranial direct current stimulation (tDCS) has been shown to modulate cortical excitability and thereby influencing motor behaviour and learning. While there is increasing knowledge about the importance of the primary motor cortex (M1) in short- and long-term motor skill learning, little is known about the role of secondary motor areas such as the supplementary and pre-supplementary motor area (SMA/pre-SMA) especially in short-term motor performance. Since SMA but not pre-SMA is directly connected to M1, we hypothesize that anodal tDCS over SMA but not pre-SMA will facilitate visuomotor learning. We applied anodal tDCS (tDCS(anodal)) over left SMA, pre-SMA or M1 (n=12 in each group) while subjects performed a visuomotor pinch force task (VPFT) with their right hand and compared VPFT performance relative to sham (tDCS(sham)). For the first time, we could show that apart from tDCS(anodal) over left M1 also SMA but not pre-SMA stimulation promotes short-term improvements in visuomotor learning relative to tDCS(sham). Our findings provide novel evidence about the role of SMA in short-term visuomotor performance. This knowledge might be beneficial in developing hypothesis-driven clinical studies in neurorehabilitation. Copyright © 2013 Elsevier Inc. All rights reserved.

  3. Disrupting pre-SMA activity impairs facial happiness recognition: an event-related TMS study.

    Science.gov (United States)

    Rochas, Vincent; Gelmini, Lauriane; Krolak-Salmon, Pierre; Poulet, Emmanuel; Saoud, Mohamed; Brunelin, Jerome; Bediou, Benoit

    2013-07-01

    It has been suggested that the left pre-supplementary motor area (pre-SMA) could be implicated in facial emotion expression and recognition, especially for laughter/happiness. To test this hypothesis, in a single-blind, randomized crossover study, we investigated the impact of transcranial magnetic stimulation (TMS) on performances of 18 healthy participants during a facial emotion recognition task. Using a neuronavigation system based on T1-weighted magnetic resonance imaging of each participant, TMS (5 pulses, 10 Hz) was delivered over the pre-SMA or the vertex (control condition) in an event-related fashion after the presentation of happy, fear, and angry faces. Compared with performances during vertex stimulation, we observed that TMS applied over the left pre-SMA specifically disrupted facial happiness recognition (FHR). No difference was observed between the 2 conditions neither for fear and anger recognition nor for reaction times (RT). Thus, interfering with pre-SMA activity with event-related TMS after stimulus presentation produced a selective impairment in the recognition of happy faces. These findings provide new insights into the functional implication of the pre-SMA in FHR, which may rely on the mirror properties of pre-SMA neurons.

  4. 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.

  5. Dissociating the Role of the pre-SMA in Response Inhibition and Switching: A Combined Online and Offline TMS Approach.

    Science.gov (United States)

    Obeso, Ignacio; Robles, Noemí; Marrón, Elena M; Redolar-Ripoll, Diego

    2013-01-01

    The pre-supplementary motor area (pre-SMA) is considered to be a key node in the cognitive control of actions that require rapid updating, inhibition, or switching, as well as working memory. It is now recognized that the pre-SMA is part of a "cognitive control" network involving the inferior frontal gyrus (IFG) and subcortical regions, such as the striatum and subthalamic nucleus. However, two important questions remain to be addressed. First, it is not clear if the main role of the pre-SMA in cognitive control lies in inhibition or switching of actions. From imaging evidence, the right pre-SMA is consistently recruited during inhibition and switching, but the extent to which it participates specifically in either of these processes is unknown. Secondly, the pre-SMA may perform inhibition and switching alone or as part of a larger brain network. The present study used online and offline transcranial magnetic stimulation (TMS) to dissociate the roles of pre-SMA in cognitive control, but also to investigate the potential contribution of connectivity between the pre-SMA and IFG. We applied continuous theta burst stimulation (cTBS) over the right IFG before participants performed a stop switching task while receiving single TMS pulses over the right pre-SMA. The results were compared to a sham cTBS session and pulses applied over the vertex region. Significant worsening of inhibition as well as response adaptation during inhibition was found when applying pulses over the pre-SMA. However, no such worsening was observed in switch trials. Additionally, after cTBS over the IFG, inhibition was also delayed, suggesting its critical necessity in stopping of actions. The results reveal a key contribution of the pre-SMA in inhibition and could suggest a dissociative role in the switching of actions. These findings indicate there is an essential union between IFG and pre-SMA during inhibition.

  6. 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

    were common to repetition in both modalities. We thus obtained three seed regions: the bilateral pre-SMA, left dorsal premotor cortex (PMd), and left ventral premotor cortex that were used to test 63 different models of effective connectivity in the premotor network for pseudoword relative to word...... repetition. The optimal model was identified with Bayesian model selection and reflected a network with driving input to pre-SMA and an increase in facilitatory drive from pre-SMA to PMd during repetition of pseudowords. The task-specific increase in effective connectivity from pre-SMA to left PMd suggests...... that the pre-SMA plays a supervisory role in the generation and subsequent sequencing of motor plans. Diffusion tensor imaging-based fiber tracking in another group of healthy volunteers showed that the functional connection between both regions is underpinned by a direct cortico-cortical anatomical connection....

  7. Functional dissociation of pre-SMA and SMA-proper in temporal processing.

    Science.gov (United States)

    Schwartze, Michael; Rothermich, Kathrin; Kotz, Sonja A

    2012-03-01

    The ability to assess temporal structure is crucial in order to adapt to an ever-changing environment. Increasing evidence suggests that the supplementary motor area (SMA) is involved in both sensory and sensorimotor processing of temporal structure. However, it is not entirely clear whether the structural differentiation of the SMA translates into functional specialization, and how the SMA relates to other systems that engage in temporal processing, namely the cerebellum and cortico-striatal circuits. Anatomically, the SMA comprises at least two subareas, the rostral pre-SMA and the caudal SMA-proper. Each displays a characteristic pattern of connections to motor and non-motor structures. Crucially, these connections establish a potential hub among cerebellar and cortico-striatal systems, possibly forming a dedicated subcortico-cortical temporal processing network. To further explore the functional role of each SMA subarea, we performed a meta-analysis of functional neuroimaging studies by contrasting activations according to whether they linked with either sensory, sensorimotor, sequential, non-sequential, explicit, non-explicit, subsecond, or suprasecond temporal processing. This procedure yielded a set of functional differences, which mirror the rostro-caudal anatomical dimension. Activations associated with sensory, non-sequential, and suprasecond temporal processing tend to locate to the rostral SMA, while the opposite is true for the caudal SMA. These findings confirm a functional dissociation of pre-SMA and SMA-proper in temporal processing. Copyright © 2011 Elsevier Inc. All rights reserved.

  8. Stimulation of the pre-SMA influences cerebral blood flow in frontal areas involved with inhibitory control of action.

    Science.gov (United States)

    Obeso, I; Cho, S S; Antonelli, F; Houle, S; Jahanshahi, M; Ko, J H; Strafella, A P

    2013-09-01

    Selection of the most appropriate response necessitates inhibition of competing or prepotent responses. It is important to characterize which cortical areas are relevant to achieve response inhibition. Using the stop signal task, previous imaging studies revealed consistent activation in the right pre-supplementary motor area (pre-SMA). However, imaging alone suffers from the limitation that it can only provide neuronal correlates and cannot establish causality between brain activation and behavior. Repetitive transcranial magnetic stimulation (rTMS) can be used to temporarily interfere with the function of a cortical area considered to play a specific role in the behavior. Thus, we combined rTMS with H(2)(15)O positron emission tomography (PET) scans during the stop signal task, to test whether rTMS-induced changes in excitability of the right pre-SMA influenced response inhibition. We found that rTMS over the pre-SMA increased the efficiency of the inhibitory control over prepotent ongoing responses. A significant interaction was present in the left inferior frontal gyrus (IFG) along with an increase in regional cerebral blood flow (rCBF) in the left pre-SMA, left IFG, right premotor and right inferior parietal cortex. These areas best fitted the path analysis model in the effective connectivity model. The results of this study suggest that stimulation of the right pre-SMA, by interfering with its activity, may have a significant impact on response inhibition. Copyright © 2013 Elsevier Inc. All rights reserved.

  9. 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.

  10. Pre-SMA actively engages in conflict processing in human: a combined study of epicortical ERPs and direct cortical stimulation.

    Science.gov (United States)

    Usami, Kiyohide; Matsumoto, Riki; Kunieda, Takeharu; Shimotake, Akihiro; Matsuhashi, Masao; Miyamoto, Susumu; Fukuyama, Hidenao; Takahashi, Ryosuke; Ikeda, Akio

    2013-04-01

    Previous non-invasive studies have proposed that the deeply seated region of the medial frontal cortex engages in conflict processing in humans, but its core region has remained to be elucidated. By means of direct cortical stimulation, which excels other techniques in temporal and spatial resolutions and in the capacity of producing transient, functional impairment even in the deeply located cortices, we attempted to obtain direct evidence that the pre-supplementary motor area (pre-SMA) actively engages in conflict processing. Subject was a patient with right frontal lobe epilepsy who underwent invasive presurgical evaluation with subdural electrodes placed on the medial and lateral frontal cortices. During a conflict task--modified Eriksen flanker task, direct cortical stimulation was delivered time-locked to the task at the inferior part of the medial superior frontal gyrus (inferior medial SFG), the superior part of the medial SFG, and the middle frontal gyrus. By adopting the session of sham stimulation that was employed as a within-block control, event-related potentials (ERPs) were recorded from the medial and lateral frontal cortices. The inferior medial SFG showed a significant ERP difference between trials with more and less conflict, while the other frontal cortices did not. Among the three stimulus sites, only stimulation of the inferior medial SFG significantly prolonged reaction time in trials with more conflict. Anatomically, the inferior medial SFG corresponded with the pre-SMA (Brodmann area 8). It was located 1-2 cm rostral to the vertical anterior commissure line where cortical stimulation elicited arrest of motion (the supplementary negative motor area). Functionally, this area corresponded to the dorso-rostral portion of the activation loci in previous neuroimaging studies focusing on conflict processing. By combining epicortical ERP recording and direct cortical stimulation in a human brain, this study, for the first time, presented one direct

  11. 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

    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 t......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...... 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...

  12. CosmoPMC: Cosmology Population Monte Carlo

    CERN Document Server

    Kilbinger, Martin; Cappe, Olivier; Cardoso, Jean-Francois; Fort, Gersende; Prunet, Simon; Robert, Christian P; Wraith, Darren

    2011-01-01

    We present the public release of the Bayesian sampling algorithm for cosmology, CosmoPMC (Cosmology Population Monte Carlo). CosmoPMC explores the parameter space of various cosmological probes, and also provides a robust estimate of the Bayesian evidence. CosmoPMC is based on an adaptive importance sampling method called Population Monte Carlo (PMC). Various cosmology likelihood modules are implemented, and new modules can be added easily. The importance-sampling algorithm is written in C, and fully parallelised using the Message Passing Interface (MPI). Due to very little overhead, the wall-clock time required for sampling scales approximately with the number of CPUs. The CosmoPMC package contains post-processing and plotting programs, and in addition a Monte-Carlo Markov chain (MCMC) algorithm. The sampling engine is implemented in the library pmclib, and can be used independently. The software is available for download at http://www.cosmopmc.info.

  13. The Role of the Supplementary Motor Region in Overt Reading: Evidence for Differential Processing in SMA-Proper and Pre-SMA as a Function of Task Demands.

    Science.gov (United States)

    Cummine, Jacqueline; Hanif, Wahab; Dymouriak-Tymashov, Inna; Anchuri, Kavya; Chiu, Stephanie; Boliek, Carol A

    2017-03-04

    A differentiation in function between the pre-SMA (i.e., cognitive load) and the SMA-proper (i.e., motor execution) has been described (Zhang et al., Cereb Cortex 22:99-111, 2012). These differential SMA functions may be influential in overt reading tasks. The present study examined the relationships between various segments of the SMA and overt reading through the modulation of task demands in an effort to explore the complexity of the print-to-speech network. Skilled reading adults (N = 15) took part in five overt reading tasks: pure regular word reading, pure exception word reading, mixed regular word and exception word reading, go/no-go reading with nonword foils and go/no-go reading with pseudohomophone foils. Five regions of interest that spanned the pre-SMA to the SMA-proper were isolated. Behaviour-function relationships were tested to examine the associations between performance (response time) and brain activity (percent signal change). Further, the coherence between feedforward (SMA) and feedback (supramarginal gyrus) regions were explored to further refine the print-to-speech network. We found that the pre-SMA was related to cognitively demanding tasks (go/no-go with pseudohomophones), whereas the SMA-proper was related to an automatized task (pure regular words). Notably, only those tasks that required information from the feedback system (i.e., mixed word lists, go/no-go tasks) showed connections between SMA regions and the supramarginal gyrus, which is in line with the role of feedback and feedforward systems in the print-to-speech network. Together, these results support the notion that the pre-SMA and SMA-proper are sensitive to reading tasks that differentially invoke higher cognitive resources (mixed word lists, go/no-go) versus automatized articulation (pure lists), respectively. We discuss our findings in the context of print-to-speech neural networks.

  14. Electromagnetic Boundaries with PEC/PMC Equivalence

    CERN Document Server

    Lindell, Ismo V

    2016-01-01

    The most general electromagnetic boundary, defined by linear and local boundary conditions, is defined in terms of conditions which can be called generalized impedance boundary conditions. Requiring that the boundary be equivalent to PEC and PMC boundaries for its two eigen-plane waves, which property is known to exist for many of its special cases, it is shown that the recently introduced Generalized Soft-and-Hard/DB (GSHDB) boundary is the most general boundary satisfying this property.

  15. PMC: Select Materialized Cells in Data Cubes

    Institute of Scientific and Technical Information of China (English)

    Hong-Song Li; Hou-Kuan Huang

    2006-01-01

    QC-Tree is one of the most storage-efficient structures for data cubes in an MOLAP system. Although QC-Tree can achieve a high compression ratio, it is still a fully materialized data cube. In this paper, an improved structure PMC is presented allowing us to materialize only a part of the cells in a QC-Tree to save more storage space. There is a notable difference between our partially materialization algorithm and traditional materialized views selection algorithms. In a traditional algorithm, when a view is selected, all the cells in this view are to be materialized. Otherwise, if a view is not selected, all the cells in this view will not be materialized. This strategy results in the unstable query performance. The presented algorithm, however, selects and materializes data in cell level, and, along with further reduced space and update cost, it can ensure a stable query performance. A series of experiments are conducted on both synthetic and real data sets. The results show that PMC can further reduce storage space occupied by the data cube, and can shorten the time to update the cube.

  16. Thermal decomposition of PMC for fiber recovery

    Energy Technology Data Exchange (ETDEWEB)

    Jody, B. J.; Daniels, E. J.; Pomykala, J. A.

    1999-10-22

    This paper describes efforts by Argonne National Laboratory to develop a process to recover carbon fibers from polymer matrix composite (PMC) materials. The polymer material in the matrix maybe a thermoplastic or a thermoset. Samples of panels containing PMC fibers were obtained and used in the bench-scale testing program. The authors tested three different methods for recovering these PMC fibers: thermal treatment, chemical degradation, and cryogenic methods (thermal shock treatment). The first two methods were effective in separating the carbon fibers from the polymeric substrate; the third method was not satisfactory. Carbon fibers separated from the polymer substrate using the thermal treatment method were submitted to Oak Ridge National Laboratory for analysis and evaluation. The results indicated that the carbon fibers had been cleanly separated from the polymer matrix. Their intrinsic density was 1.8473 g/cm{sup 3} and their electrical resistivity was 0.001847 ohm-cm, compared to an intrinsic density of 1.75--1.9 gm/cm{sup 3} and an electrical resistivity of 0.0002--0.002 ohm-cm for virgin fibers produced from polyacrylonitrile (PAN). Although they were not sure that the samples they processed were originally produced from PAN, they used the PAN fibers for comparison. It was also demonstrated that the surface of the recovered fibers could be reactivated to energy levels equivalent to those of reactivated virgin fibers from PAN. A comparison of the mechanical properties of the recovered fibers (without surface treatment) with those of surface-treated virgin fibers from PAN revealed that the ultimate tensile strength and the elongation at brake values are about 1/3 the values for the virgin fibers. The modulus for the recycled fibers (31.4 million pounds per square inch [psi]) was about the same as that for the virgin PAN fibers (31.2 million psi). The reason for the lower tensile strength and elongation is not clear; the authors plan to investigate it further

  17. [Technical Representative - Monthly PMC Issues Reports : Rocky Mountain Arsenal NWR

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — This collection of documents contains the Monthly PMC Issues reports for the Rocky Mountain Arsenal compiled by the Technical Representative. Reports in this...

  18. Direct Observations of PMC Local Time Variations by Aura OMI

    Science.gov (United States)

    DeLand, Matthew T.; Shettle, Eric P.; Thomas, Gary E.; Olivero, John J.

    2010-01-01

    The Ozone Monitoring Instrument (OMI) on the Aura satellite obtains unique measurements for polar mesospheric cloud (PMC) analysis. Its wide cross-track viewing swath and high along-track spatial resolution makes it possible to directly evaluate PMC occurrence frequency and brightness variations between 6S" and 8S' latitude as a function of local time over a 12-14 h continuous period. OMI PMC local time variations are closely coupled to concurrent variations in measurement scattering angle, so that ice phase function effects must be considered when interpreting the observations. Two different phase functions corresponding to bright and faint clouds are examined in this analysis. OMI observations show maximum frequency and albedo values at 8-10 h local time in the Northern Hemisphere, with decreasing amplitude at higher latitudes. Southern Hemisphere values reach a minimum at 18-20 h LT. Larger variations are seen in Northern Hemisphere data. No statistically significant longitudinal dependence was seen.

  19. Direct Observations of PMC Local Time Variations by Aura OMI

    Science.gov (United States)

    DeLand, Matthew T.; Shettle, Eric P.; Thomas, Gary E.; Olivero, John J.

    2010-01-01

    The Ozone Monitoring Instrument (OMI) on the Aura satellite obtains unique measurements for polar mesospheric cloud (PMC) analysis. Its wide cross-track viewing swath and high along-track spatial resolution makes it possible to directly evaluate PMC occurrence frequency and brightness variations between 6S" and 8S' latitude as a function of local time over a 12-14 h continuous period. OMI PMC local time variations are closely coupled to concurrent variations in measurement scattering angle, so that ice phase function effects must be considered when interpreting the observations. Two different phase functions corresponding to bright and faint clouds are examined in this analysis. OMI observations show maximum frequency and albedo values at 8-10 h local time in the Northern Hemisphere, with decreasing amplitude at higher latitudes. Southern Hemisphere values reach a minimum at 18-20 h LT. Larger variations are seen in Northern Hemisphere data. No statistically significant longitudinal dependence was seen.

  20. 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.

  1. 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.

  2. MICROHARDNESS AND ADHESION STRENGTH OF PMC'S COATINGS BY NiCr ALLOY

    National Research Council Canada - National Science Library

    Aseel A Kareem; Zaina Raheem

    2016-01-01

      The use of polymer matrix composites (PMC's) in the gas flow path of advanced turbine engines offers significant benefits for aircraft engine performance but their useful lifetime is limited by their poor environmental resistance...

  3. Functional Characterization of an Aspergillus fumigatus Calcium Transporter (PmcA) that Is Essential for Fungal Infection

    Science.gov (United States)

    Dinamarco, Taísa Magnani; Freitas, Fernanda Zanolli; Almeida, Ricardo S.; Brown, Neil Andrew; dos Reis, Thaila Fernanda; Ramalho, Leandra Naira Zambelli; Savoldi, Marcela; Goldman, Maria Helena S.; Bertolini, Maria Célia; Goldman, Gustavo Henrique

    2012-01-01

    Aspergillus fumigatus is a primary and opportunistic pathogen, as well as a major allergen, of mammals. The Ca+2-calcineurin pathway affects virulence, morphogenesis and antifungal drug action in A. fumigatus. Here, we investigated three components of the A. fumigatus Ca+2-calcineurin pathway, pmcA,-B, and -C, which encode calcium transporters. We demonstrated that CrzA can directly control the mRNA accumulation of the pmcA-C genes by binding to their promoter regions. CrzA-binding experiments suggested that the 5′-CACAGCCAC-3′ and 5′-CCCTGCCCC-3′ sequences upstream of pmcA and pmcC genes, respectively, are possible calcineurin-dependent response elements (CDREs)-like consensus motifs. Null mutants were constructed for pmcA and -B and a conditional mutant for pmcC demonstrating pmcC is an essential gene. The ΔpmcA and ΔpmcB mutants were more sensitive to calcium and resistant to manganese and cyclosporin was able to modulate the sensitivity or resistance of these mutants to these salts, supporting the interaction between calcineurin and the function of these transporters. The pmcA-C genes have decreased mRNA abundance into the alveoli in the ΔcalA and ΔcrzA mutant strains. However, only the A. fumigatus ΔpmcA was avirulent in the murine model of invasive pulmonary aspergillosis. PMID:22649543

  4. State-dependent and timing-dependent bidirectional associative plasticity in the human SMA-M1 network.

    Science.gov (United States)

    Arai, Noritoshi; Müller-Dahlhaus, Florian; Murakami, Takenobu; Bliem, Barbara; Lu, Ming-Kuei; Ugawa, Yoshikazu; Ziemann, Ulf

    2011-10-26

    The supplementary motor area (SMA-proper) plays a key role in the preparation and execution of voluntary movements. Anatomically, SMA-proper is densely reciprocally connected to primary motor cortex (M1), but neuronal coordination within the SMA-M1 network and its modification by external perturbation are not well understood. Here we modulated the SMA-M1 network using MR-navigated multicoil associative transcranial magnetic stimulation in healthy subjects. Changes in corticospinal excitability were assessed by recording motor evoked potential (MEP) amplitude bilaterally in a hand muscle. We found timing-dependent bidirectional Hebbian-like MEP changes during and for at least 30 min after paired associative SMA-M1 stimulation. MEP amplitude increased if SMA stimulation preceded M1 stimulation by 6 ms, but decreased if SMA stimulation lagged M1 stimulation by 15 ms. This associative plasticity in the SMA-M1 network was highly topographically specific because paired associative stimulation of pre-SMA and M1 did not result in any significant MEP change. Furthermore, associative plasticity in the SMA-M1 network was strongly state-dependent because it required priming by near-simultaneous M1 stimulation to occur. We conclude that timing-dependent bidirectional associative plasticity is demonstrated for the first time at the systems level of a human corticocortical neuronal network. The properties of this form of plasticity are fully compatible with spike-timing-dependent plasticity as defined at the cellular level. The necessity of priming may reflect the strong interhemispheric connectivity of the SMA-M1 network. Findings are relevant for better understanding reorganization and potentially therapeutic modification of neuronal coordination in the SMA-M1 network after cerebral lesions such as stroke.

  5. 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.

  6. An evaluation of Prospective Motion Correction (PMC for high resolution quantitative MRI

    Directory of Open Access Journals (Sweden)

    Martina F Callaghan

    2015-03-01

    Full Text Available Quantitative imaging aims to provide in vivo neuroimaging biomarkers with high research and diagnostic value that are sensitive to underlying tissue microstructure. In order to use these data to examine intra-cortical differences or to define boundaries between different myelo-architectural areas, high resolution data are required. The quality of such measurements is degraded in the presence of motion hindering insight into brain microstructure. Correction schemes are therefore vital for high resolution, whole brain coverage approaches that have long acquisition times and greater sensitivity to motion. Here we evaluate the use of prospective motion correction (PMC via an optical tracking system to counter intra-scan motion in a high resolution (800µm isotropic multi-parameter mapping (MPM protocol. Data were acquired on six volunteers using a 2x2 factorial design permuting the following conditions: PMC on/off and motion/no motion. In the presence of head motion, PMC-based motion correction considerably improved the quality of the maps as reflected by fewer visible artefacts and improved consistency. The precision of the maps, parameterised by the coefficient of variation in cortical sub-regions, showed improvements of 11-24% in the presence of deliberate head motion. Importantly, in the absence of motion the PMC system did not introduce extraneous artefacts into the quantitative maps. The PMC system based on optical tracking offers a robust approach to minimising motion artefacts in quantitative anatomical imaging without extending scan times. Such a robust motion correction scheme is crucial in order to achieve the ultra-high resolution required of quantitative imaging for cutting edge in vivo histology applications.

  7. 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.

  8. High Thermal Conductivity Polymer Matrix Composites (PMC) for Advanced Space Radiators

    Science.gov (United States)

    Shin, E. Eugene; Bowman, Cheryl; Beach, Duane

    2007-01-01

    High temperature polymer matrix composites (PMC) reinforced with high thermal conductivity (approx. 1000 W/mK) pitch-based carbon fibers are evaluated for a facesheet/fin structure of large space radiator systems. Significant weight reductions along with improved thermal performance, structural integrity and space durability toward its metallic counterparts were envisioned. Candidate commercial resin systems including Cyanate Esters, BMIs, and polyimide were selected based on thermal capabilities and processability. PMC laminates were designed to match the thermal expansion coefficient of various metal heat pipes or tubes. Large, but thin composite panels were successfully fabricated after optimizing cure conditions. Space durability of PMC with potential degradation mechanisms was assessed by simulated thermal aging tests in high vacuum, 1-3 x 10(exp -6) torr, at three temperatures, 227 C, 277 C, and 316 C for up to one year. Nanocomposites with vapor-grown carbon nano-fibers and exfoliated graphite flakes were attempted to improve thermal conductivity (TC) and microcracking resistance. Good quality nanocomposites were fabricated and evaluated for TC and durability including radiation resistance. TC was measured in both in-plan and thru-the-thickness directions, and the effects of microcracks on TC are also being evaluated. This paper will discuss the systematic experimental approaches, various performance-durability evaluations, and current subcomponent design and fabrication/manufacturing efforts.

  9. INTEGRATED COI S200 - Hi-NiCalon FIBER WITH AN S200 MATRIX (POLYMER MATRIX COMPOSITE - PMC) / AETB 1

    Science.gov (United States)

    2003-01-01

    INTEGRATED COI S200 - Hi-NiCalon FIBER WITH AN S200 MATRIX (POLYMER MATRIX COMPOSITE - PMC) / AETB 16 (FOAM CORE) / CARBON REINFORCED CYANOESTER (CERAMIC MATRIX COMPOSITE - CMC) HOT STRUCTURE, PANEL 884-1: SAMPLE 1

  10. GSM(m,1)(m=1,2)模型的数值解%Numeriacl Solution of GSM (m, 1)(m= 1,2)Model

    Institute of Scientific and Technical Information of China (English)

    吴强; 刘炳琪

    2001-01-01

    The prediction accuracy can be improved by using the spline function to correct the residue of GM (m,1)(m=1,2). Numerical Solution of GSM (m,1)(m=1,2)Modle is given.%本文用样条函数对GM(m,1)(m=1,2)模型的残差序列进行插值拟合,得到GSM(m,1)(m=1,2)模型的数值解.

  11. Simultaneous PMC and PMSE observations with a ground-basedlidar and SuperDARN HF radar over Syowa Station, Antarctica

    Science.gov (United States)

    Suzuki, Hidehiko; Nakamura, Takuji; Tsutsumi, Masaki; Kawahara, Takuya D.; Ogawa, Tadahiko; Tomikawa, Yoshihiro; Ejiri, Mitsumu K.; Sessai Yukimatu, Akira; Abo, Makoto

    2012-07-01

    A Rayleigh-Raman lidar system had been installed by the 52nd JapaneseAntarctic Research Expedition on February, 2011 at Syowa Station Antarctica(69.0°S, 39.5°E). Polar Mesospheric Cloud (PMC) was detected by the lidar at22:30UT (+3hr for LT) on Feb 4th, 2011, the first day of a routineoperation. This event is the first time to detect PMC over Syowa Station bya lidar. In the same night, SuperDARN HF radar with oblique incidence beamsalso detected Polar Mesosphere Summer Echoes (PMSEs) during 21:30UT to23:00UT. Although these signals were detected at different times andlocations, PMC motion estimated using horizontal wind velocities obtained bya collocated MF radar strongly suggests that they have a common origin (i.e.ice particle). We consider that this event occurred in the end of PMCactivity period at Syowa Station in the austral summer season (2010-2011),since the lidar did not detected any PMC signals on other days in February,2011. This is consistent with satellite-born PMC observations by AIM/CIPSand atmospheric temperature observations by AURA/MLS instruments.

  12. Treatment of severe active systemic lupus erythematosus by PMC therapy combined Langchuang Fuzheng Jiedu capsule: a clinical observation

    Institute of Scientific and Technical Information of China (English)

    宋欣伟

    2013-01-01

    Objective To evaluate the efficacy and safety of PMC therapy (Prednisone,Methotrexate,Chloroquine) combined Langchuang Fuzheng Jiedu Capsule (LFJC) ,thus choosing a better therapy of integrative medicine for SLE in the period of glucocorticoid use.Methods Sixty active SLE patients were randomly assigned to two groups,the control group and the treatment group.Those in the control group received PMC therapy (As for Prednisone,it was given at the daily dose of 1 mg/kg till 2weeks after the condition being stable or after 8 weeks of

  13. Two-day period fluctuation of PMC occurrence over Syowa Station, Antarctica observed by a ground-based lidar and AIM satellite.

    Science.gov (United States)

    Nakamura, T.; Suzuki, H.; Tsutsumi, M.; Ejiri, M. K.; Tomikawa, Y.; Abo, M.; Kawahara, T.; Tsuda, T. T.; Nishiyama, T.

    2014-12-01

    A Rayleigh/Raman lidar system has been operated by the Japanese Antarctic Research Expedition (JARE) since February, 2011 (JARE 52nd) in Syowa Station Antarctica (69.0S, 39.5E). The lidar system consists of a pulsed Nd:YAG laser (355nm) as a transmitter and two telescopes with four photo multiplier tubes which are to detect Rayleigh scattered light from low and high atmosphere at 355 nm and N2 Raman emission at 387nm. Polar Mesospheric Cloud (PMC) was detected by the lidar at 22:30UT (+3hr for LT) on Feb 4th, 2011, the first day of a routine operation. This event was the first time to detect PMC over Syowa Station by a lidar [Suzuki et al., Ann. Geophys., 2013]. However, signal to noise ratio (SNR) of the PMC event was not so good due to large shot noises from daytime background signals. Moreover, a receiver system was designed mainly for nighttime observations. In this way, observation of PMC during the midnight sun, which also corresponds to most frequent PMC season, was difficult. Thus, to improve SNR of the PMC observation with the lidar during daytime, a narrow band-pass Fabry-Perot etalon unit has been developed and installed in the receiver system on Dec 2013 by JARE 55th. By using this new system, clear PMC signals were successfully detected under daylight condition during the period of summer operation of JARE55th. During this period of 53 days (from 17 Dec. 2013 to 7 Feb. 2014), only 11 days were with a clear sky and suitable for PMC observation. Thus, it was difficult to study temporal variations on a PMC activity only by using the lidar data. Fortunately, NASA's AIM satellite had passed near Syowa Station and provided with complimentary PMC data during observation gap of the lidar. By combining our lidar data with the AIM/CIPS data, nearly continuous monitoring of PMC variability over Syowa Station was achieved for period between 13th and 18th in January 2014. PMC occurrence with an interval of two days over Syowa Station during the period was clearly

  14. Validation of a GPU-based Monte Carlo code (gPMC) for proton radiation therapy: clinical cases study

    Science.gov (United States)

    Giantsoudi, Drosoula; Schuemann, Jan; Jia, Xun; Dowdell, Stephen; Jiang, Steve; Paganetti, Harald

    2015-03-01

    Monte Carlo (MC) methods are recognized as the gold-standard for dose calculation, however they have not replaced analytical methods up to now due to their lengthy calculation times. GPU-based applications allow MC dose calculations to be performed on time scales comparable to conventional analytical algorithms. This study focuses on validating our GPU-based MC code for proton dose calculation (gPMC) using an experimentally validated multi-purpose MC code (TOPAS) and compare their performance for clinical patient cases. Clinical cases from five treatment sites were selected covering the full range from very homogeneous patient geometries (liver) to patients with high geometrical complexity (air cavities and density heterogeneities in head-and-neck and lung patients) and from short beam range (breast) to large beam range (prostate). Both gPMC and TOPAS were used to calculate 3D dose distributions for all patients. Comparisons were performed based on target coverage indices (mean dose, V95, D98, D50, D02) and gamma index distributions. Dosimetric indices differed less than 2% between TOPAS and gPMC dose distributions for most cases. Gamma index analysis with 1%/1 mm criterion resulted in a passing rate of more than 94% of all patient voxels receiving more than 10% of the mean target dose, for all patients except for prostate cases. Although clinically insignificant, gPMC resulted in systematic underestimation of target dose for prostate cases by 1-2% compared to TOPAS. Correspondingly the gamma index analysis with 1%/1 mm criterion failed for most beams for this site, while for 2%/1 mm criterion passing rates of more than 94.6% of all patient voxels were observed. For the same initial number of simulated particles, calculation time for a single beam for a typical head and neck patient plan decreased from 4 CPU hours per million particles (2.8-2.9 GHz Intel X5600) for TOPAS to 2.4 s per million particles (NVIDIA TESLA C2075) for gPMC. Excellent agreement was

  15. 富士通选用PMC-Sierra的城域网传输半导体器件

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    PMC-Sierra公司(Nasdaq:PMCS)宣布,富士通公司已选取PMC-Sierra的城域传输半导体方案,用于其城域光通信旗舰产品FLASHWAVE 7500可重构光分插复用器(ROADM)和FLASHWAVE 4500多工服务供应平台(MSPP)。FLASHWAVE 7500 ROADM使用PMC—Sierra CHESS Ⅲ芯片组。将完整的SONET分插复用器(ADM)功能集成在一个Flexponder接口卡上,而具互补性的FLASHWAVE 4500 MSPP不仅使用CHESSⅢ芯片组,还用到了PMC-Sierra的CHESS宽带芯片组。CHESS宽带芯片组可实现高容量VT1.5疏导,将数据和TDM流量传送到SONET/SDH支路.以满足下一代MSPP的需求。

  16. M$_1$ - M* correlation in galaxy clusters

    CERN Document Server

    Trevese, D; Appodia, B

    1994-01-01

    Photographic F band photometry of a sample of 36 Abell clusters has been used to study the relation between the magnitude M_1 of the brightest cluster member and the Schechter function parameter M^*. Clusters appear segregated in the M_1-M^* plane according to their Rood \\& Sastry class. We prove on a statistical basis that on average, going from early to late RS classes, M_1 becomes brighter while M^* becomes fainter. The result agrees with the predictions of galactic cannibalism models, never confirmed by previous analyses.

  17. Characterization of Compass M-1 signals

    NARCIS (Netherlands)

    Hauschild, A.; Montenbruck, O.; Sleewaegen, J.-M.; Huisman, L.; Teunissen, P.J.G.

    2011-01-01

    An analysis of observations from China’s first medium earth orbit satellite Compass M-1 is presented, with main focus on the first orbit and clock solution for this satellite. The orbit is computed from laser ranging measurements. Based on this orbit solution, the apparent clock offset is estimated

  18. Tool for Generation of MAC/GMC Representative Unit Cell for CMC/PMC Analysis

    Science.gov (United States)

    Murthy, Pappu L. N.; Pineda, Evan J.

    2016-01-01

    This document describes a recently developed analysis tool that enhances the resident capabilities of the Micromechanics Analysis Code with the Generalized Method of Cells (MAC/GMC) 4.0. This tool is especially useful in analyzing ceramic matrix composites (CMCs), where higher fidelity with improved accuracy of local response is needed. The tool, however, can be used for analyzing polymer matrix composites (PMCs) as well. MAC/GMC 4.0 is a composite material and laminate analysis software developed at NASA Glenn Research Center. The software package has been built around the concept of the generalized method of cells (GMC). The computer code is developed with a user friendly framework, along with a library of local inelastic, damage, and failure models. Further, application of simulated thermomechanical loading, generation of output results, and selection of architectures to represent the composite material have been automated to increase the user friendliness, as well as to make it more robust in terms of input preparation and code execution. Finally, classical lamination theory has been implemented within the software, wherein GMC is used to model the composite material response of each ply. Thus, the full range of GMC composite material capabilities is available for analysis of arbitrary laminate configurations as well. The primary focus of the current effort is to provide a graphical user interface (GUI) capability that generates a number of different user-defined repeating unit cells (RUCs). In addition, the code has provisions for generation of a MAC/GMC-compatible input text file that can be merged with any MAC/GMC input file tailored to analyze composite materials. Although the primary intention was to address the three different constituents and phases that are usually present in CMCs-namely, fibers, matrix, and interphase-it can be easily modified to address two-phase polymer matrix composite (PMC) materials where an interphase is absent. Currently, the

  19. Analytic closures for M1 neutrino transport

    Science.gov (United States)

    Murchikova, E. M.; Abdikamalov, E.; Urbatsch, T.

    2017-08-01

    Carefully accounting for neutrino transport is an essential component of many astrophysical studies. Solving the full transport equation is too expensive for most realistic applications, especially those involving multiple spatial dimensions. For such cases, resorting to approximations is often the only viable option for obtaining solutions. One such approximation, which recently became popular, is the M1 method. It utilizes the system of the lowest two moments of the transport equation and closes the system with an ad hoc closure relation. The accuracy of the M1 solution depends on the quality of the closure. Several closures have been proposed in the literature and have been used in various studies. We carry out an extensive study of these closures by comparing the results of M1 calculations with precise Monte Carlo calculations of the radiation field around spherically symmetric protoneutron star models. We find that no closure performs consistently better or worse than others in all cases. The level of accuracy that a given closure yields depends on the matter configuration, neutrino type and neutrino energy. Given this limitation, the maximum entropy closure by Minerbo on average yields relatively accurate results in the broadest set of cases considered in this work.

  20. M1 muscarinic receptor activation mediates cell death in M1-HEK293 cells.

    Science.gov (United States)

    Graham, E Scott; Woo, Kerhan K; Aalderink, Miranda; Fry, Sandie; Greenwood, Jeffrey M; Glass, Michelle; Dragunow, Mike

    2013-01-01

    HEK293 cells have been used extensively to generate stable cell lines to study G protein-coupled receptors, such as muscarinic acetylcholine receptors (mAChRs). The activation of M1 mAChRs in various cell types in vitro has been shown to be protective. To further investigate M1 mAChR-mediated cell survival, we generated stable HEK293 cell-lines expressing the human M1 mAChR. M1 mAChRs were efficiently expressed at the cell surface and efficiently internalised within 1 h by carbachol. Carbachol also induced early signalling cascades similar to previous reports. Thus, ectopically expressed M1 receptors behaved in a similar fashion to the native receptor over short time periods of analysis. However, substantial cell death was observed in HEK293-M1 cells within 24 h after carbachol application. Death was only observed in HEK cells expressing M1 receptors and fully blocked by M1 antagonists. M1 mAChR-stimulation mediated prolonged activation of the MEK-ERK pathway and resulted in prolonged induction of the transcription factor EGR-1 (>24 h). Blockade of ERK signalling with U0126 did not reduce M1 mAChR-mediated cell-death significantly but inhibited the acute induction of EGR-1. We investigated the time-course of cell death using time-lapse microscopy and xCELLigence technology. Both revealed the M1 mAChR cytotoxicity occurs within several hours of M1 activation. The xCELLigence assay also confirmed that the ERK pathway was not involved in cell-death. Interestingly, the MEK blocker did reduce carbachol-mediated cleaved caspase 3 expression in HEK293-M1 cells. The HEK293 cell line is a widely used pharmacological tool for studying G-protein coupled receptors, including mAChRs. Our results highlight the importance of investigating the longer term fate of these cells in short term signalling studies. Identifying how and why activation of the M1 mAChR signals apoptosis in these cells may lead to a better understanding of how mAChRs regulate cell-fate decisions.

  1. "m=1" coatings for neutron guides

    OpenAIRE

    Cooper-Jensen, C.P.; Vorobiev, A.; Klinkby, Esben Bryndt; Kapaklis, V.; Wilkens, H.; Rats, D.; Hjörvarsson, B.; Kirstein, O.; Bentley, Philip

    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 therm...

  2. Particle dynamics in the Eastern Mediterranean Sea: A synthesis based on light transmission, PMC, and POC archives (1991 2001)

    Science.gov (United States)

    Karageorgis, Aristomenis P.; Gardner, Wilford D.; Georgopoulos, Dimitris; Mishonov, Alexey V.; Krasakopoulou, Evangelia; Anagnostou, Christos

    2008-02-01

    During the last two decades light transmission (LT) data have been collected routinely in the Eastern Mediterranean Sea, within the framework of several research projects. A procedure was developed to obtain beam attenuation coefficient due to particles ( cp) at 660-670 nm adjusted for variations in mid-depth 'clear' water and instrumental drifts. Data from 3146 stations occupied between 1991 and 2001 were converted to a common format for the analysis of particulate matter (PM) temporal and spatial distribution patterns. The data were separated into 'wet' (December-May) and 'dry' (June-November) periods. The horizontal distribution of beam cp at various depths revealed clearly higher values in the surface nepheloid layer (SNL) in the vicinity of river mouths during the 'wet' period, whilst the increase was negligible during the 'dry' period. In contrast, the bottom nepheloid layer (BNL; 1-10 m above bottom) appeared to be turbid throughout the year, particularly on the continental shelves receiving riverine discharge. This feature is attributed to resuspension and advection of recently deposited bottom sediments due to waves and currents. However, the Eastern Mediterranean as a whole is impoverished in PM in the water column, particularly at depths >200 m. The behavior of surface-water cp revealed a strong relationship to mesoscale dynamic features. Cyclonic eddies, which upwell nutrient-rich waters toward the surface, favor primary production, which was identified as elevated beam cp values. Beam cp was correlated with PM concentration (PMC) and particulate organic carbon (POC) concentration obtained by bottle sampling. Although there were regional differences in the correlations, no significant seasonal variations were observed. Two generic equations were generated that can be used for a first-order estimate of PMC and POC from historical LT measurements conducted in the area, provided that data are handled according to the proposed methodology.

  3. "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......V. Materials like diamond and Be have higher neutron scattering density than Ni, have smaller absorption cross section and when a neutron is absorbed they emit much less gamma ray and at lower energies. We present results, both theoretically and experimentally, comparing Ni with Be and preliminary results...

  4. PMC- FISHs in Hybrids of Tetraploid Cultivated and Diploid Wild Gossypium Species%四倍体栽培棉与二倍体野生棉杂种PMC-FISH研究

    Institute of Scientific and Technical Information of China (English)

    凌键; 王坤波; 邹美娟; 宋国立; 王春英; 彭仁海; 刘方; 黎绍惠; 张香娣; 王玉红

    2009-01-01

    首次将PMC-FISH(花粉母细胞荧光原位杂交)技术应用于四倍体栽培棉与二倍体野生棉杂交所形成的三倍体杂种棉F1中,成功的鉴定了目标染色体中的单价体、双价体、多价体,还发现在非目标染色体上有星状和片段状的杂交信号.在以A组棉基因组DNA作为探针的PMC-FISH中,分别对三倍体杂种棉F1及其母本四倍体栽培棉的减数分裂中期I的染色体构型进行了鉴定.结果显示,四个三倍体杂种棉F1的减数分裂时期染色体的构型分别是:陆地棉(AD)1×雷蒙德氏棉(D5)为1IIIaad + 1IIaa + 4IIad + 7IIdd + 5Ⅰa + 7Ⅰd;海岛棉(AD)2×旱地棉(D4)为1Ⅴaaaad +1IIIadd + 2IIad + 8IIdd + 6Ⅰa + 5Ⅰd;陆地棉(AD)1×澳洲棉(C3)为2IIIadd (adc or acc) + 1IIaa + 9Ⅰa + 4IIcc (dc or dd) + 14Ⅰd (c);陆地棉(AD)1×南岱华棉(C1-n)为:1IIaa + 1IIad (ac)+ 10Ⅰa + 6IIcc (dc or dd) + 13Ⅰd (c).然而,两个四倍体棉染色体的构型都是13IIaa + 13IIdd.上述结果还显示, AD×D的两个杂种组合中,二价体多,单价体少,AD×C的两个杂种组合中,二价体少,单价体多;并且AD×D型杂种中A亚组染色体单体的数目比其在AD×C型杂种中的更少.这说明,与C染色体组相比较,D染色体组与四倍体棉种的亲缘关系更近.同时,我们的结果也证明PMC-FISH技术在分析三倍体杂种棉F1的亲缘关系中起着不可取代的作用.%PMC-FISH (pollen mother cell-fluorescence in situ hybridization) technology was firstly applied to identify probed chromosomes in univalent, bivalent and multivalent, as well as to distinguish star- or fragment-like hybridization signals from non-probed chromosomes in four triploid F1 hybrids produced by cultivated allotetraploid cotton crossed with different diploid cotton species in the genus Gossypium. Using genomic DNA from A genome species as probe, the meiotic chromosome configurations in metaphase Ⅰof four triploid F1 hybrids were identified as 1Ⅲaad + 1Ⅱaa + 4

  5. Simultaneous PMC and PMSE observations with a ground-based lidar and SuperDARN HF radar at Syowa Station, Antarctica

    Directory of Open Access Journals (Sweden)

    H. Suzuki

    2013-10-01

    Full Text Available A Rayleigh–Raman lidar system was installed in January 2011 at Syowa Station, Antarctica (69.0° S, 39.6° E. Polar mesospheric clouds (PMCs were detected by lidar at around 22:30 UTC (LT −3 h on 4 February 2011, which was the first day of observation. This was the first detection of PMCs over Syowa Station by lidar. On the same day, a Super Dual Auroral Radar Network (SuperDARN HF radar with oblique-incidence beams detected polar mesospheric summer echoes (PMSE between 21:30 and 23:00 UTC. This event is regarded as the last PMC activity around Syowa Station during the austral summer season (2010–2011, since no other PMC signals were detected by lidar in February 2011. This is consistent with results of PMC and mesopause temperature observations by satellite-born instruments of AIM (Aeronomy of Ice in the Mesosphere/CIPS (Cloud Imaging and Particle Size and AURA/MLS (Microwave Limb Sounder and horizontal wind measurements taken by a separate MF radar. Doppler velocity of PMSE observed by the HF radar showed motion toward Syowa Station (westward. This westward motion is consistent with the wind velocities obtained by the MF radar. However, the PMSE region showed horizontal motion from a north-to-south direction during the PMC event. This event indicates that the apparent horizontal motion of the PMSE region can deviate from neutral wind directions and observed Doppler velocities.

  6. Simultaneous PMC and PMSE observations with a ground-based lidar and SuperDARN HF radar at Syowa Station, Antarctica

    Science.gov (United States)

    Suzuki, H.; Nakamura, T.; Ejiri, M. K.; Ogawa, T.; Tsutsumi, M.; Abo, M.; Kawahara, T. D.; Tomikawa, Y.; Yukimatu, A. S.; Sato, N.

    2013-10-01

    A Rayleigh-Raman lidar system was installed in January 2011 at Syowa Station, Antarctica (69.0° S, 39.6° E). Polar mesospheric clouds (PMCs) were detected by lidar at around 22:30 UTC (LT -3 h) on 4 February 2011, which was the first day of observation. This was the first detection of PMCs over Syowa Station by lidar. On the same day, a Super Dual Auroral Radar Network (SuperDARN) HF radar with oblique-incidence beams detected polar mesospheric summer echoes (PMSE) between 21:30 and 23:00 UTC. This event is regarded as the last PMC activity around Syowa Station during the austral summer season (2010-2011), since no other PMC signals were detected by lidar in February 2011. This is consistent with results of PMC and mesopause temperature observations by satellite-born instruments of AIM (Aeronomy of Ice in the Mesosphere)/CIPS (Cloud Imaging and Particle Size) and AURA/MLS (Microwave Limb Sounder) and horizontal wind measurements taken by a separate MF radar. Doppler velocity of PMSE observed by the HF radar showed motion toward Syowa Station (westward). This westward motion is consistent with the wind velocities obtained by the MF radar. However, the PMSE region showed horizontal motion from a north-to-south direction during the PMC event. This event indicates that the apparent horizontal motion of the PMSE region can deviate from neutral wind directions and observed Doppler velocities.

  7. Putative PmrA and PmcA are important for normal growth, morphogenesis and cell wall integrity, but not for viability in Aspergillus nidulans.

    Science.gov (United States)

    Jiang, Hechun; Liu, Feifei; Zhang, Shizhu; Lu, Ling

    2014-11-01

    P-type Ca(2+)-transporting ATPases are Ca(2+) pumps, extruding cytosolic Ca(2+) to the extracellular environment or the intracellular Ca(2+) store lumens. In budding yeast, Pmr1 (plasma membrane ATPase related), and Pmc1 (plasma membrane calcium-ATPase) cannot be deleted simultaneously for it to survive in standard medium. Here, we deleted two putative Ca(2+) pumps, designated AnPmrA and AnPmcA, from Aspergillus nidulans, and obtained the mutants ΔanpmrA and ΔanpmcA, respectively. Then, using ΔanpmrA as the starting strain, the promoter of its anpmcA was replaced with the alcA promoter to secure the mutant ΔanpmrAalcApmcA or its anpmcA was deleted completely to produce the mutant ΔanpmrAΔpmcA. Different from the case in Saccharomyces cerevisiae, double deletion of anpmrA and anpmcA was not lethal in A. nidulans. In addition, deletion of anpmrA and/or anpmcA had produced growth defects, although overexpression of AnPmc1 in ΔanpmrAalcApmcA could not restore the growth defects that resulted from the loss of AnPmrA. Moreover, we found AnPmrA was indispensable for maintenance of normal morphogenesis, especially in low-Ca(2+)/Mn(2+) environments. Thus, our findings suggest AnPmrA and AnPmcA might play important roles in growth, morphogenesis and cell wall integrity in A. nidulans in a different way from that in yeasts.

  8. Cancer risks posed by aflatoxin M1.

    Science.gov (United States)

    Hsieh, D P; Cullen, J M; Hsieh, L S; Shao, Y; Ruebner, B H

    1985-01-01

    The suspect milk-borne carcinogen, aflatoxin M1 (AFM), was produced and isolated from the rice culture of the fungus Aspergillus flavus NRRL3251 for confirmation and determination of the potency of its carcinogenicity in the male adult Fischer rat. The carcinogen was mixed into an agar-based, semisynthetic diet at 0, 0.5, 5, and 50 ppb (microgram/kg) and was fed to groups of animals continuously for 19-21 months. Aflatoxin B1 (AFB), of which AFM is a metabolite, at 50 ppb was used as a positive control. Hepatocarcinogenicity of AFM was detected at 50 ppb, but not at 5 or 0.5 ppb, with a potency of 2-10% that of AFB. A low incidence of intestinal adenocarcinomas was found in the AFM 50 ppb group, but not in any other groups. At 0.5 ppb, the action level enforced by the U.S.A. Food and Drug Administration, AFM induced no liver lesions in the rats but stimulated the animals' growth. On the average, the rats in the 0.5 ppb group weighed 11% (p less than 0.001) more than those in the control group. This increased growth was associated with increased feed intake. Based on the biological activity of AFM at the relevant low doses and the estimated level of human exposure to AFM through consumption of milk, the cancer risk posed by this contaminant for human adults is assessed to be very low. For infants, further studies are warranted because milk constitutes the major ingredient of the infant diet and because infant animals have been shown to be more sensitive to the carcinogenicity of AFB than adult animals.

  9. 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.

  10. On the nonexistence of $[\\binom{2m}{m-1}, 2m, \\binom{2m-1}{m-1}]$, $m$ odd, complex orthogonal design

    CERN Document Server

    Li, Yuan

    2011-01-01

    Complex orthogonal designs (CODs) are used to construct space-time block codes. COD $\\mathcal{O}_z$ with parameter $[p, n, k]$ is a $p\\times n$ matrix, where nonzero entries are filled by $\\pm z_i$ or $\\pm z^*_i$, $i = 1, 2,..., k$, such that $\\mathcal{O}^H_z \\mathcal{O}_z = (|z_1|^2+|z_2|^2+...+|z_k|^2)I_{n \\times n}$. Adams et al. in "The final case of the decoding delay problem for maximum rate complex orthogonal designs," IEEE Trans. Inf. Theory, vol. 56, no. 1, pp. 103-122, Jan. 2010, first proved the nonexistence of $[\\binom{2m}{m-1}, 2m, \\binom{2m-1}{m-1}]$, $m$ odd, COD. Combining with the previous result that decoding delay should be an integer multiple of $\\binom{2m}{m-1}$, they solved the final case $n \\equiv 2 \\pmod 4$ of the decoding delay problem for maximum rate complex orthogonal designs. In this paper, we give another proof of the nonexistence of COD with parameter $[\\binom{2m}{m-1}, 2m, \\binom{2m-1}{m-1}]$, $m$ odd. Our new proof is based on the uniqueness of $[\\binom{2m}{m-1}, 2m-1, \\binom{...

  11. The conformation of acetylated virginiamycin M1 and virginiamycin M1 in explicit solvents.

    Science.gov (United States)

    Ng, Chai Ann; Zhao, Wen; Dang, Jason; Bergdahl, Mikael; Separovic, Frances; Brownlee, Robert T C; Metzger, Robert P

    2007-05-01

    The three-dimensional structure of acetylated virginiamycin M(1) (acetylated VM1) in chloroform and in a water/acetonitrile mixture (83:17 v/v) have been established through 2D high resolution NMR experiments and molecular dynamics modeling and the results compared with the conformation of the antibiotic VM1 in the same and other solvents. The results indicated that acetylation of the C-14 OH group of VM1 caused it to rotate about 90 degrees from the position it assumed in non-acetylated VM1. The conformation of both VM1 and acetylated VM1 appear to flatten in moving from a nonpolar to polar solvent. However, the acetylated form has a more hydrophobic nature. The acetylated VM1 in chloroform and in water/acetonitrile solution had a similar configuration to that of VM1 bound to 50S ribosomes and to the Vat(D) active sites as previously determined by X-ray crystallography. Docking studies of VM1 to the 50S ribosomal binding site and the Vat(D) gave conformations very similar to those derived from X-ray crystallographic studies. The docking studies with acetylated VM1 suggested the possibility of a hydrogen bond from the acetyl carbonyl group oxygen of acetylated VM1 to the 2' hydroxyl group of ribose of adenosine 2538 at the ribosomal VM1 binding site. No hydrogen bonds between acetylated VM1 and the Vat(D) active sites were found; the loss of this binding interaction partly accounts for the release of the product from the active site.

  12. Qualification Lab Testing on M1 Abrams Engine Oil Filters

    Science.gov (United States)

    2016-11-01

    UNCLASSIFIED QUALIFICATION LAB TESTING ON M1 ABRAMS ENGINE OIL FILTERS FINAL REPORT TFLRF No. 483 by Kristi K. Rutta U.S...the originator. UNCLASSIFIED QUALIFICATION LAB TESTING ON M1 ABRAMS ENGINE OIL FILTERS FINAL REPORT TFLRF No. 483 by Kristi K...TITLE AND SUBTITLE Qualification Lab Testing on M1 Abrams Engine Oil Filter 5a. CONTRACT NUMBER W56HZV-15-C-0030 5b. GRANT NUMBER 5c. PROGRAM

  13. Develop Efficient Leak Proof M1 Abrams Plenum Seal

    Science.gov (United States)

    2014-05-07

    UNCLASSIFIED UNCLASSIFIED ER-GLSV11389-001.docx Develop Efficient Leak Proof M1 Abrams Plenum Seal SBIR Phase I: Topic A13-061...Leak Proof M1 Abrams Plenum Seal Christian Muehfeld Steve Pennala Great Lakes Sound & Vibration, Inc. 47140 North Main Street Houghton, MI 49931 ER...061. The purpose of this report is to show the feasibility of developing an efficient, leak proof plenum seal for the M1 Abrams . It also shows the

  14. Genomic Characterization of Campylobacter jejuni strain M1

    DEFF Research Database (Denmark)

    Friis, Carsten; Wassenaar, Gertrude Maria; Javed, Muhammad A.

    2010-01-01

    publicly available. Compared to these, M1 is closest to strain 81116. Based on the 13 genome sequences, we have identified the C. jejuni pan-genome, as well as the core genome, the auxiliary genes, and genes unique between strains M1 and 81116. The pan-genome contains 2,427 gene families, whilst the core...

  15. FoxM1 Regulates Mammary Luminal Cell Fate

    Directory of Open Access Journals (Sweden)

    Janai R. Carr

    2012-06-01

    Full Text Available Elevated expression of FoxM1 in breast cancer correlates with an undifferentiated tumor phenotype and a negative clinical outcome. However, a role for FoxM1 in regulating mammary differentiation was not known. Here, we identify another function of FoxM1, the ability to act as a transcriptional repressor, which plays an important role in regulating the differentiation of luminal epithelial progenitors. Regeneration of mammary glands with elevated levels of FoxM1 leads to aberrant ductal morphology and expansion of the luminal progenitor pool. Conversely, knockdown of FoxM1 results in a shift toward the differentiated state. FoxM1 mediates these effects by repressing the key regulator of luminal differentiation, GATA-3. Through association with DNMT3b, FoxM1 promotes methylation of the GATA-3 promoter in an Rb-dependent manner. This study identifies FoxM1 as a critical regulator of mammary differentiation with significant implications for the development of aggressive breast cancers.

  16. On (2m + 1)-variable symmetric Boolean functions with submaximum algebraic immunity 2m-1

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    All (2m +1)-variable symmetric Boolean functions with submaximal algebraic immunity 2m-1 are described and constructed. The total number of such Boolean functions is 32 ·22m-3 +3m-2 · 24 - 2 for m≥2.

  17. An Investigation on the Use of a Laser Ablation Treatment on Metallic Surfaces and the Influence of Temperature on Fracture Toughness of Hybrid Co-Cured Metal-PMC Interfaces

    Science.gov (United States)

    Connell, John; Palmieri, Frank; Truong, Hieu; Ochoa, Ozden; Lagoudas, Dimitris

    2015-01-01

    Hybrid composite laminates that contain alternating layers of titanium alloys and carbon fabric reinforced polyimide matrix composites (PMC) are excellent candidates for light-weight, high-temperature structural materials for high-speed aerospace vehicles. The delamination resistance of the hybrid titanium-PMC interface is of crucial consideration for structural integrity during service. Here, we report the first investigations on the use of laser ablation in combination with sol-gel treatment technique on Ti/NiTi foil surfaces in co-cured hybrid polyimide matrix composite laminates. Mode-I and mode-II fracture toughness of the hybrid Ti/NiTi-PMC interface as a function of temperature were determined via experimental testing and finite element analysis.

  18. Diverse Effects on M1 Signaling and Adverse Effect Liability within a Series of M1 Ago-PAMs.

    Science.gov (United States)

    Rook, Jerri M; Abe, Masahito; Cho, Hyekyung P; Nance, Kellie D; Luscombe, Vincent B; Adams, Jeffrey J; Dickerson, Jonathan W; Remke, Daniel H; Garcia-Barrantes, Pedro M; Engers, Darren W; Engers, Julie L; Chang, Sichen; Foster, Jarrett J; Blobaum, Anna L; Niswender, Colleen M; Jones, Carrie K; Conn, P Jeffrey; Lindsley, Craig W

    2017-01-10

    Both historical clinical and recent preclinical data suggest that the M1 muscarinic acetylcholine receptor is an exciting target for the treatment of Alzheimer's disease and the cognitive and negative symptom clusters in schizophrenia; however, early drug discovery efforts targeting the orthosteric binding site have failed to afford selective M1 activation. Efforts then shifted to focus on selective activation of M1 via either allosteric agonists or positive allosteric modulators (PAMs). While M1 PAMs have robust efficacy in rodent models, some chemotypes can induce cholinergic adverse effects (AEs) that could limit their clinical utility. Here, we report studies aimed at understanding the subtle structural and pharmacological nuances that differentiate efficacy from adverse effect liability within an indole-based series of M1 ago-PAMs. Our data demonstrate that closely related M1 PAMs can display striking differences in their in vivo activities, especially their propensities to induce adverse effects. We report the discovery of a novel PAM in this series that is devoid of observable adverse effect liability. Interestingly, the molecular pharmacology profile of this novel PAM is similar to that of a representative M1 PAM that induces severe AEs. For instance, both compounds are potent ago-PAMs that demonstrate significant interaction with the orthosteric site (either bitopic or negative cooperativity). However, there are subtle differences in efficacies of the compounds at potentiating M1 responses, agonist potencies, and abilities to induce receptor internalization. While these differences may contribute to the differential in vivo profiles of these compounds, the in vitro differences are relatively subtle and highlight the complexities of allosteric modulators and the need to focus on in vivo phenotypic screening to identify safe and effective M1 PAMs.

  19. Broad analgesic activity of a novel, selective M1 agonist.

    Science.gov (United States)

    Wood, Michael W; Martino, Giovanni; Coupal, Martin; Lindberg, Mattias; Schroeder, Patricia; Santhakumar, Vijayaratnam; Valiquette, Manon; Sandin, Johan; Widzowski, Daniel; Laird, Jennifer

    2017-09-01

    Although the muscarinic receptor family has long been a source of potentially compelling targets for small molecule drug discovery, it was difficult to achieve agonist selectivity within the family. A new class of M1 muscarinic agonists has emerged, and these compounds have been characterized as agonists that activate the receptor at an allosteric site. Members of this class of M1 agonists have been shown to be selective across the muscarinic receptors. However, upon introduction of a novel pharmacologic mechanism, it is prudent to ensure that no new off-target activities have arisen, particularly within the context of in vivo experiments. Reported here, is the in vitro and in vivo characterization of a novel M1 agonist tool compound, PPBI, and demonstrations that the primary biological effects of PPBI are mediated through M1. PPBI reverses d-amphetamine locomotor activity, but fails to do so in transgenic mice that do not express M1. PPBI also reverses a natural deficit in a rat cognition model at a level of exposure which also activates cortical circuitry. Most notably, PPBI is analgesic in a variety of rat and mouse models and the analgesic effect of PPBI is reversed by an M1-preferring antagonist and an M1-selective toxin. Finally, the pharmacokinetic/pharmacodynamic measures of PPBI are compared across multiple endpoints which highlights that activity in models of psychosis and pain require higher exposures than that required in the cognition model. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Selectivity of oxomemazine for the M1 muscarinic receptors.

    Science.gov (United States)

    Lee, S W; Woo, C W; Kim, J G

    1994-12-01

    The binding characteristics of pirenzepine and oxomemazine to muscarinic receptor were studied to evaluate the selectivity of oxomemazine for the muscarinic receptor subtypes in rat cerebral microsomes. Equilibrium dissociation constant (KD) of (-)-[3H]quinuclidinyl benzilate([3H]QNB) determined from saturation isotherms was 64 pM. Analysis of the pirenzepine inhibition curve of [3H]QNB binding to cerebral microsome indicated the presence of two receptor subtypes with high (Ki = 16 nM, M1 receptor) and low (Ki = 400 nM, M3 receptor) affinity for pirenzepine. Oxomemazine also identified two receptor subtypes with about 20-fold difference in the affinity for high (Ki = 84 nM, OH receptor) and low (Ki = 1.65 microM, OL receptor) affinity sites. The percentage populations of M1 and M3 receptors to the total receptors were 61:39, and those of OH and OL receptors 39:61, respectively. Both pirenzepine and oxomemazine increased the KD value for [3H]QNB without affecting the binding site concentrations and Hill coefficient for the [3H]QNB binding. Oxomemazine had a 10-fold higher affinity at M1 receptors than at M3 receptors, and pirenzepine a 8-fold higher affinity at OH receptors than at OL receptors. Analysis of the shallow competition binding curves of oxomemazine for M1 receptors and pirenzepine for OL receptors yielded that 69% of M1 receptors were of OH receptors and the remaining 31% of OL receptors, and that 29% of OL receptors were of M1 receptors and 71% of M3 receptors. However, M3 for oxomemazine and OH for pirenzepine were composed of a uniform population. These results suggest that oxomemazine could be classified as a selective drug for M1 receptors and also demonstrate that rat cerebral microsomes contain three different subtypes of M1, M3 and the other site which is different from M1, M2 and M3 receptors.

  1. M1.3--a small scaffold for DNA origami .

    Science.gov (United States)

    Said, Hassan; Schüller, Verena J; Eber, Fabian J; Wege, Christina; Liedl, Tim; Richert, Clemens

    2013-01-07

    The DNA origami method produces programmable nanoscale objects that form when one long scaffold strand hybridizes to numerous oligonucleotide staple strands. One scaffold strand is dominating the field: M13mp18, a bacteriophage-derived vector 7249 nucleotides in length. The full-length M13 is typically folded by using over 200 staple oligonucleotides. Here we report the convenient preparation of a 704 nt fragment dubbed "M1.3" as a linear or cyclic scaffold and the assembly of small origami structures with just 15-24 staple strands. A typical M1.3 origami is large enough to be visualized by TEM, but small enough to show a cooperativity in its assembly and thermal denaturation that is reminiscent of oligonucleotide duplexes. Due to its medium size, M1.3 origami with globally modified staples is affordable. As a proof of principle, two origami structures with globally 5'-capped staples were prepared and were shown to give higher UV-melting points than the corresponding assembly with unmodified DNA. M1.3 has the size of a gene, not a genome, and may function as a model for gene-based nanostructures. Small origami with M1.3 as a scaffold may serve as a workbench for chemical, physical, and biological experiments.

  2. Surface properties of new virginiamycin M(1) derivatives.

    Science.gov (United States)

    Nott, Katherine; Paquot, Michel; Dufour, Samuel; Eeman, Marc; Deleu, Magali

    2009-03-01

    Three kinds of derivatives of the M(1) factor of virginiamycin have been synthesised: esters with long chain fatty acids, oximes with modified polar amino acids and bis-derivatives with both the ester and oxime function. The study of the surface tension time dependence of M(1) and its derivatives has shown that it is necessary to enhance simultaneously the hydrophobicity and the hydrophilicity of M(1) to render M(1) surface-active. A structure/function relationship study of the surface-active bis-derivatives has shown that enhancing the hydrophobicity of the molecule led to slower adsorption kinetics, higher stability of the monolayers formed and a better capacity to penetrate a membrane model. The repulsive electrostatic forces due to the presence of charges on the amino acids linked to M(1) lead to higher surface tensions, a greater molecular area at the interface and lower penetration into a membrane model. This study has demonstrated that modifying systematically the hydrophobicity and hydrophilicity of a non surface-active molecule allows the production of surface-active derivatives.

  3. Genomic characterization of Campylobacter jejuni strain M1.

    Directory of Open Access Journals (Sweden)

    Carsten Friis

    Full Text Available Campylobacter jejuni strain M1 (laboratory designation 99/308 is a rarely documented case of direct transmission of C. jejuni from chicken to a person, resulting in enteritis. We have sequenced the genome of C. jejuni strain M1, and compared this to 12 other C. jejuni sequenced genomes currently publicly available. Compared to these, M1 is closest to strain 81116. Based on the 13 genome sequences, we have identified the C. jejuni pan-genome, as well as the core genome, the auxiliary genes, and genes unique between strains M1 and 81116. The pan-genome contains 2,427 gene families, whilst the core genome comprised 1,295 gene families, or about two-thirds of the gene content of the average of the sequenced C. jejuni genomes. Various comparison and visualization tools were applied to the 13 C. jejuni genome sequences, including a species pan- and core genome plot, a BLAST Matrix and a BLAST Atlas. Trees based on 16S rRNA sequences and on the total gene families in each genome are presented. The findings are discussed in the background of the proven virulence potential of M1.

  4. 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.

  5. Concerning the Integral dx/x[superscript m] (1+x)

    Science.gov (United States)

    Walters, William; Huber, Michael

    2010-01-01

    Consider the integral dx/x[superscript m] (1+x). In the "CRC Standard Mathematical Tables," this integral can require repeated integral evaluations. Enter this integral into your favourite computer algebra system, and the results may be unrecognizable. In this article, we seek to provide a simpler evaluation for integrals of this form. We state up…

  6. Theory of the M = 1 Kink Mode in Toroidal Plasma

    NARCIS (Netherlands)

    de Blank, H. J.; Schep, T. J.

    1991-01-01

    The energy principle of ideal magnetohydrodynamics (MHD) is used to study the ideal MHD stability of the m = 1 internal kink mode in a toroidal plasma. The equilibrium configurations that are considered allow for a broad region where the safety factor q is close to unity. This region may extend to t

  7. Concerning the Integral dx/x[superscript m] (1+x)

    Science.gov (United States)

    Walters, William; Huber, Michael

    2010-01-01

    Consider the integral dx/x[superscript m] (1+x). In the "CRC Standard Mathematical Tables," this integral can require repeated integral evaluations. Enter this integral into your favourite computer algebra system, and the results may be unrecognizable. In this article, we seek to provide a simpler evaluation for integrals of this form. We state up…

  8. The E2/M1 ratio in {Delta} photoproduction

    Energy Technology Data Exchange (ETDEWEB)

    Hoblit, S. [Brookhaven National Lab., Upton, NY (United States). Physics Dept.]|[Univ. of Virginia, Charlottesville, VA (United States). Dept. of Physics; Blanpied, G. [Univ. of South Carolina, Columbia, SC (United States). Dept. of Physics; Blecher, M. [Virginia Polytechnic Inst. and State Univ., Blacksburg, VA (United States). Physics Dept.] [and others; LEGS Collaboration

    1997-10-01

    New high-precision measurements of p({rvec {gamma}}, {pi}) and p({rvec {gamma}}, {gamma}) cross sections and beam asymmetries have been combined with other polarization ratios in a simultaneous analysis of both reactions. The E2/M1 mixing ratio for the n {r_arrow} {Delta} transition extracted from this analysis is EMR = {minus}3.0% {+-} 0.3 (stat+sys) {+-} 0.2 (model).

  9. The E2/M1 ratio in {Delta} photoproduction

    Energy Technology Data Exchange (ETDEWEB)

    Sandorfi, A.M. [Brookhaven National Lab., Upton, NY (United States). Physics Dept.; Blanpied, G. [Univ. of South Carolina, Columbia, SC (United States). Dept. of Physics; Blecher, M. [Virginia Polytechnic Inst. and State Univ., Blacksburg, VA (United States). Physics Dept.] [and others; LEGS Collaboration

    1997-08-01

    The properties of the transition from the nucleon to the {Delta}(1232) serve as a benchmark for models of nucleon structure. To first order, N {r_arrow} {Delta} photo-excitation is dominated by a simple M1 quark spin-flip transition. At higher order, small L = 2 components in the N and {Delta} wavefunctions allow this excitation to proceed via an electric quadrupole transition. Since Nucleon models differ greatly on the mechanisms used to generate these L = 2 components,, the ratio of E2/M1 transitions (EMR) provides a sensitive test for structure models. Here, new high-precision measurements of p({rvec {gamma}}, {pi}) and p({rvec {gamma}}, {gamma}) cross sections and beam asymmetries have been combined with other polarization ratios in a simultaneous analysis of both reactions. Compton scattering has provided two important new constraints on the photo-pion amplitude. The E2/M1 mixing ratio for the N {r_arrow} {Delta} transition extracted from this analysis is EMR = {minus}3.0% {+-} 0.3 (stat+sys) {+-} 0.2 (model).

  10. Effect of the radial plasma nonuniformity on the propagation of guided m = + 1 and m = - 1 modes in helicon discharges

    Science.gov (United States)

    Aliev, Yu. M.; Krämer, M.

    2016-10-01

    Theoretical as well as numerical analyses of the full set of Maxwell's equations is carried out to study non-axisymmetric ( m ≠ 0 ) guided modes in radially nonuniform helicon (HE) discharges. Unlike the axisymmetric (m = 0) modes, these modes reveal a non-reciprocal behavior with respect to the azimuthal direction. We develop the conditions for propagation and non-propagation of the various modes in the helicon parameter range, thereby focussing on the important role of the radial density gradient. Three types of modes occurring in different parameter ranges are described, i.e., the helicon (HE) mode, the electrostatic (ES) or Trivelpiece-Gould mode, and the locally coupled (LC) mode that is characterized by mode coupling (MC) in a certain region of the plasma density profile. In contrast to m = + 1 modes, the parameter range of m = - 1 modes is much more restricted as rather high densities are needed for the propagation of the helicon and LC modes. An important issue of the investigations is the rf power coupling and absorption via the various modes. Computations based on a simple antenna-plasma model show that the axial wavenumber of the antenna determines decisively which type of mode is excited. In case of LC mode excitation, the dominant role of the MC layer for the absorption is demonstrated. Finally, the rf power coupling to helicon modes is studied. The density limit for m = - 1 helicon mode propagation and the narrow magnetic field profiles of these modes are the main reasons why the rf power absorption in helicon discharges occurs via m = + 1 helicon modes.

  11. Electrochemical immunochip sensor for aflatoxin M1 detection.

    Science.gov (United States)

    Parker, Charlie O; Lanyon, Yvonne H; Manning, Mary; Arrigan, Damien W M; Tothill, Ibtisam E

    2009-07-01

    An investigation into the fabrication, electrochemical characterization, and development of a microelectrode array (MEA) immunosensor for aflatoxin M(1) is presented in this paper. Gold MEAs (consisting of 35 microsquare electrodes with 20 microm x 20 microm dimensions and edge-to-edge spacing of 200 microm) together with on-chip reference and counter electrodes were fabricated using standard photolithographic methods. The MEAs were then characterized by cyclic voltammetry, and the behavior of the on-chip electrodes were evaluated. The microarray sensors were assessed for their applicability to the development of an immunosensor for the analysis of aflatoxin M(1) directly in milk samples. Following the sensor surface silanization, antibodies were immobilized by cross-linking with 1,4-phenylene diisothiocyanate (PDITC). Surface characterization was conducted by electrochemistry, fluorescence microscopy, scanning electron microscopy (SEM), and atomic force microscopy (AFM). A competitive enzyme linked immunosorbent assay (ELISA) assay format was developed on the microarray electrode surface using the 3,3,5',5'-tetramethylbenzidine dihyrochloride (TMB)/H(2)O(2) electrochemical detection scheme with horseradish peroxidase (HRP) as the enzyme label. The performance of the assay and the microarray sensor were characterized in pure buffer conditions before applying to the milk samples. With the use of this approach, the detection limit for aflatoxin M(1) in milk was estimated to be 8 ng L(-1), with a dynamic detection range of 10-100 ng L(-1), which meets present legislative limits of 50 ng L(-1). The milk interference with the sensor surface was also found to be minimal. These devices show high potential for development of a range of new applications which have previously only been detected using elaborate instrumentation.

  12. A review of aflatoxin M1 in liquid milk

    OpenAIRE

    2015-01-01

    Mycotoxins continue to pose a health concern via human exposure to contaminated food. Aflatoxin M1 (AFM1), the hydroxylated metabolite of aflatoxin B1 (AFB1), may be found in the milk of dairy cattle and other mammals. In humans, AFM1 is excreted through the feces, urine, and in the case of lactating mothers, also in breast milk after consumption of aflatoxin contaminated food. Concentration of AFM1 in milk is a function of several factors, namely: animal type, milking day, milk yield, season...

  13. 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

  14. a Comparison of δ13C & pMC Values for Ten Cretaceous-Jurassic Dinosaur Bones from Texas to Alaska USA, China and Europe with that of Coal and Diamonds Presented in the 2003 Agu Meeting

    Science.gov (United States)

    Miller, H. R.; Dennett, R.; de Pontcharra, J.; Giertych, M.; Kline, O.; van Oosterwych, M. C.; Owen, H.; Taylor, J. D.

    2014-12-01

    There is convincing evidence that soft tissue and other biomolecules can survive long periods of fossilization by their interaction with blood iron and/or carbonate absorption. Here are presented the results of investigations showing that ancient biomolecules and their decay products contain significantly more pMC's (% modern 14C) than diamond and coal presented during a poster session held at the AGU 2003 SF convention. The title was: The Enigma of the Ubiquity of 14C in organic samples older than 100,000 K. The given range for five diamonds from Botswana and South Africa ranged from 0.096 to 0.146 pMC. Ten coal specimens from the United States from the Eocene to Pennsylvanian geologic interval yielded 0.1 to 0.46 pMC's. In our extensive field and lab study ten dinosaurs from Texas to Alaska, and China yielded much higher pMC's of 0.76 to 5.59 after pretreatment to remove modern contaminants. When 2g of a Belgium Mosasaur from Europe was pretreated to remove contaminants the pMC was 4.68 or 24,600 RC years on Lund Un AMS in Sweden (Lindgren et al. 2011, PloS ONE, page 9). The endogenous sources of dinosaur pMC's were further enhanced by the δ13C range of -20.1 to -23.8 for collagen, 16.6-28.4 for bulk organic and -3.1 to -9.1 for CO3 fractions. The δ13C values compare favorably to δ13C values of -23 to -27 in a similar study of dinosaur δ13C values from the Judith River formation in Alberta, Canada that (Ostrom et al. 1993, Geology, v. 21). . Diamonds from South America (Taylor-Southon, Nuclear Instruments 2007 ) yielded ages of 66,000 to 80,000 years leaving little doubt that at least the dinosaur ages of 22,020 ± 50 to 39,230 ± 140 were not machine error or a result of contamination anymore than the coal samples. This data explains more clearly why such biomolecules have persisted and therefore should not be ignored as the implications are of utmost importance to science and humanity. Thus the experimental results presented here demonstrate the need for

  15. KARAKTERISASI SIFAT FISIS MEMBRAN POLIMER MATRIK KOMPOSIT(PMC DARI KARBON AKTIF TEMPURUNG KELAPA UNTUK ADSORBSI LOGAM BERAT PADA MINYAK GORENG BEKAS

    Directory of Open Access Journals (Sweden)

    Vivi Nurmayanti

    2014-05-01

    Full Text Available Minyak goreng yang sudah berulangkali dipanaskan akan berwarna hitam dan mengandung logam-logam berat. Untuk meremajakannya diperlukan teknologi alternatif yang mampu mereduksi logam berat pada minyak goreng bekas. Salah satunya adalah membran PMC yang digunakansebagai filter. Membran di uji sifat fisis (debit aliran, kerapatan, porositas dengan variasi ukuran mesh dan komposisi karbon aktif tempurung kelapa. Matrik berasal dari campuran 0.3 gr PEG, 5 ml PVA, dan 5 ml Aquades. Filler berupa serbuk karbon aktif berasal dari limbah tempurung kelapa. Membran di buat dengan variasi ukuran mesh 60, 100, 120 mesh dan komposisi 1, 3, dan 5 gr. Karbon aktif diperoleh dari tempurung kelapa dengan teknik pemanasan pada temperatur 500o C dan aktifasi kimia dengan larutan H3PO4 5 M. Hasil terbaik ditunjukkan pada membran dengan penambahan karbon aktif  5 gram 120 mesh yang memiliki efektifitas penyaringan paling baik dan adsorbsi logam berat paling maksimal. Debit aliran semakin meningkat dengan nilai 0.0333 (ml/menit dan kerapatan membran semakin kecil 0.95534 (gr/cm dengan porositas 0.39 %. Hasil AAS menunjukan logam Cu mengalami penurunan kadar logam sebesar 0.0819 mg/L dan logam Fe 0.0285 mg/L. Membran ini merupakan membran mikrofiltrasi dengan rata-rata pori-pori 160.4 nm yang mampu mereduksi partikel dan bakteri dengan ukuran 400 nm hingga 2 µm

  16. 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.

  17. 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.

  18. 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.

  19. [The BION-M1 project: overview and first results].

    Science.gov (United States)

    Sychev, V N; Ilyin, E A; Yarmanova, E N; Rakov, D V; Ushakov, I B; Kirilin, A N; Orlov, O I; Grigoriev, A I

    2014-01-01

    Biosatellite BION-M1 was launched on April 19 and landed on May 19, 2013. The mission program was largely a continuation of the earlier flown 11 BION projects, FOTON-M2 and FOTON-M3. The biosatellite was inhabited by a great variety of living organisms used for experiments and studies in gravitational physiology, gravitational biology, biotechnology, astrobiology and radiation biology, dosimetry and spectrometry. This was the first time in the history of national biology and physiology when male mice C57bl/6 were chosen for a long-term space experiment focused upon molecular biology investigations. Unfortunately, because of technical failures during the flight a part of the animals were lost. However, the major objectives were attained through reconsideration of biomaterial division among investigators and completion of virtually the total scope of investigations.

  20. Unstable $m=1$ modes of counter-rotating Keplerian discs

    CERN Document Server

    Gulati, Mamta; Sridhar, S

    2012-01-01

    We study the linear $m=1$ counter-rotating instability in a two-component, nearly Keplerian disc. Our goal is to understand these \\emph{slow} modes in discs orbiting massive black holes in galactic nuclei. They are of interest not only because they are of large spatial scale--and can hence dominate observations--but also because they can be growing modes that are readily excited by accretion events. Self-gravity being nonlocal, the eigenvalue problem results in a pair of coupled integral equations, which we derive for a two-component softened gravity disc. We solve this integral eigenvalue problem numerically for various values of mass fraction in the counter-rotating component. The eigenvalues are in general complex, being real only in the absence of the counter-rotating component, or imaginary when both components have identical surface density profiles. Our main results are as follows: (i) the pattern speed appears to be non negative, with the growth (or damping) rate being larger for larger values of the ...

  1. The conformational flexibility of the antibiotic virginiamycin M(1).

    Science.gov (United States)

    Dang, Jason; Metzger, Robert P; Brownlee, Robert T C; Ng, Chai Ann; Bergdahl, Mikael; Separovic, Frances

    2005-07-01

    The antibiotic virginiamycin is a combination of two molecules, virginiamycin M(1) (VM1) and virginiamycin S(1) (VS1) or analogues, which function synergistically by binding to bacterial ribosomes and inhibiting bacterial protein synthesis. Both VM1 and VS1 dissolve poorly in water and are soluble in more hydrophobic solvents. We have recently reported that the 3D conformation of VM1 in CDCl(3) solution differs markedly from the conformation bound to a VM1 binding enzyme and to 50S ribosomes as found by X-ray crystallographic studies. We now report the results of further NMR studies and subsequent molecular modeling of VM1 dissolved in CD(3)CN/H(2)O and compare the structure with that in CD(3)OD and CDCl(3). The conformations of VM1 in CD(3)CN/H(2)O, CD(3)OD and CDCl(3) differ substantially from one another and from the bound form, with the aqueous form most like the bound structure. We propose that the flexibility of the VM1 molecule in response to environmental conditions contributes to its effectiveness as an antibiotic.

  2. The m=1 amplituhedron and cyclic hyperplane arrangements

    CERN Document Server

    Karp, Steven N

    2016-01-01

    The (tree) amplituhedron A(n,k,m) is the image in the Grassmannian Gr(k,k+m) of the totally nonnegative part of Gr(k,n), under a (map induced by a) linear map which is totally positive. It was introduced by Arkani-Hamed and Trnka in 2013 in order to give a geometric basis for the computation of scattering amplitudes in N=4 supersymmetric Yang-Mills theory. When k+m=n, the amplituhedron is isomorphic to the totally nonnegative Grassmannian, and when k=1, the amplituhedron is a cyclic polytope. While the case m=4 is most relevant to physics, the amplituhedron is an interesting mathematical object for any m. In this paper we study it in the case m=1. We start by taking an orthogonal point of view and define a related "B-amplituhedron" B(n,k,m), which we show is isomorphic to A(n,k,m). We use this reformulation to describe the amplituhedron in terms of sign variation. We then give a cell decomposition of the amplituhedron A(n,k,1) using the images of a collection of distinguished cells of the totally nonnegative ...

  3. Abundances of Planetary Nebula M1-42

    CERN Document Server

    Pottasch, S R; Roellig, T L

    2007-01-01

    The spectra of the planetary nebula M1-42 is reanalysed using spectral measurements made in the mid-infrared with the Spitzer Space Telescope. The aim is to determine the chemical composition of this object. We also make use of ISO, IUE and ground based spectra. Abundances determined from the mid- and far-infrared lines, which are insensitive to electron temperature, are used as the basis for the determination of the composition, which are found to substantially differ from earlier results. High values of neon, argon and sulfur are found. They are higher than in other PN, with the exception of NGC6153, a nebula of very similar abundances. The high values of helium and nitrogen found indicate that the second dredge-up and hot bottom burning has occurred in the course of evolution and that the central star was originally more massive than 4Msun. The present temperature and luminosity of the central star is determined and at first sight may be inconsistent with such a high mass.

  4. Thermoelectric waste heat recovery from an M1 Abrams tank

    Science.gov (United States)

    Stokes, C. David; Thomas, Peter M.; Baldasaro, Nicholas G.; Mantini, Michael J.; Venkatasubramanian, Rama; Barton, Michael D.; Cardine, Christopher V.; Walker, Grayson W.

    2012-06-01

    The addition of advanced sensors, targeting systems and electronic countermeasures to military vehicles has created a strategic need for additional electric power. By incorporating a thermoelectric (TE) waste heat recovery system to convert available exhaust heat to electricity, increased electric power needs can be met without reducing the energy efficiency of the vehicle. This approach allows existing vehicles to be upgraded without requiring a complete re-design of the engine and powertrain to support the integration of advanced electronic sensors and systems that keep the performance at the state of the art level. RTI has partnered with General Dynamics Land Systems and Creare, Inc. under an Army Research Lab program to develop a thermoelectric exhaust waste heat recovery system for the M1 Abrams tank. We have designed a reduced-scale system that was retrofitted to the tank and generated 80W of electric power on the vehicle operating on a test track by capturing a portion of the exhaust heat from the Honeywell/Lycoming AGT-1500 gas turbine engine.

  5. Modulation of Effects of Intermittent Theta Burst Stimulation Applied Over Primary Motor Cortex (M1) by Conditioning Stimulation of the Opposite M1

    Science.gov (United States)

    Ragert, Patrick; Camus, Mickael; Vandermeeren, Yves; Dimyan, Michael A.; Cohen, Leonardo G.

    2009-01-01

    The excitability of the human primary motor cortex (M1) as tested with transcranial magnetic stimulation (TMS) depends on its previous history of neural activity. Homeostatic plasticity might be one important physiological mechanism for the regulation of corticospinal excitability and synaptic plasticity. Although homeostatic plasticity has been demonstrated locally within M1, it is not known whether priming M1 could result in similar homeostatic effects in the homologous M1 of the opposite hemisphere. Here, we sought to determine whether down-regulating excitability (priming) in the right (R) M1 with 1-Hz repetitive transcranial magnetic stimulation (rTMS) changes the excitability-enhancing effect of intermittent theta burst stimulation (iTBS) applied over the homologous left (L) M1. Subjects were randomly allocated to one of four experimental groups in a sham-controlled parallel design with real or sham R M1 1-Hz TMS stimulation always preceding L M1 iTBS or sham by about 10 min. The primary outcome measure was corticospinal excitability in the L M1, as measured by recruitment curves (RCs). Secondary outcome measures included pinch force, simple reaction time, and tapping speed assessed in the right hand. The main finding of this study was that preconditioning R M1 with 1-Hz rTMS significantly decreased the excitability-enhancing effects of subsequent L M1 iTBS on RCs. Application of 1-Hz rTMS over R M1 alone and iTBS over L M1 alone resulted in increased RC in L M1 relative to sham interventions. The present findings are consistent with the hypothesis that homeostatic mechanisms operating across hemispheric boundaries contribute to regulate motor cortical function in the primary motor cortex. PMID:19474173

  6. The TNM 8 M1b and M1c classification for non-small cell lung cancer in a cohort of patients with brain metastases.

    Science.gov (United States)

    Nieder, C; Hintz, M; Oehlke, O; Bilger, A; Grosu, A L

    2017-09-01

    According to the recent TNM 8 classification, patients with metastatic non-small cell lung cancer (NSCLC) and single extrathoracic metastasis should be classified as stage M1b, while those with 2 or more metastases comprise stage M1c. The purpose of this study was to analyze the impact of this classification in patients with brain metastases. This retrospective study included 172 patients treated with individualized approaches. Actuarial survival was calculated. Uni- and multivariate analyses were performed. Thirty patients (17%) were staged as M1b. Those with squamous cell cancer were more likely to harbor M1b disease (29%, adenocarcinoma 14%, other histology 17%, p = 0.16). Median survival was 5.4 months (8.0 months in case of M1b disease and 4.5 months in case of M1c disease, p = 0.001). Multivariate analysis confirmed the role of M1b stage. M1b patients managed with upfront surgery or radiosurgery had significantly longer median survival than those who received whole-brain irradiation (21.0 vs. 3.5 months, p = 0.0001) and the potential to survive beyond 5 years. We found the M1b classification to provide clinically relevant information. The multivariate analysis suggested that patients with M1b disease, better performance status and younger age have better survival.

  7. Experimental Conditions: SE37_S18_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available opes SE37_S18 PSEUDO: Unlabeled and labeled Medicago samples for metabolite annotation using ShiftedIonsFind...17_M1), and for Medicago samples labeled by 13C (S05_M1), 15N (S07_M1), 28O (S10_M1), and 34S (S13_M1) are used. SE37_DS4 Labeled peak search by ShiftedIonsFinder ...

  8. Anti-CD47 Treatment Stimulates Phagocytosis of Glioblastoma by M1 and M2 Polarized Macrophages and Promotes M1 Polarized Macrophages In Vivo.

    Directory of Open Access Journals (Sweden)

    Michael Zhang

    Full Text Available Tumor-associated macrophages (TAMs represent an important cellular subset within the glioblastoma (WHO grade IV microenvironment and are a potential therapeutic target. TAMs display a continuum of different polarization states between antitumorigenic M1 and protumorigenic M2 phenotypes, with a lower M1/M2 ratio correlating with worse prognosis. Here, we investigated the effect of macrophage polarization on anti-CD47 antibody-mediated phagocytosis of human glioblastoma cells in vitro, as well as the effect of anti-CD47 on the distribution of M1 versus M2 macrophages within human glioblastoma cells grown in mouse xenografts. Bone marrow-derived mouse macrophages and peripheral blood-derived human macrophages were polarized in vitro toward M1 or M2 phenotypes and verified by flow cytometry. Primary human glioblastoma cell lines were offered as targets to mouse and human M1 or M2 polarized macrophages in vitro. The addition of an anti-CD47 monoclonal antibody led to enhanced tumor-cell phagocytosis by mouse and human M1 and M2 macrophages. In both cases, the anti-CD47-induced phagocytosis by M1 was more prominent than that for M2. Dissected tumors from human glioblastoma xenografted within NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice and treated with anti-CD47 showed a significant increase of M1 macrophages within the tumor. These data show that anti-CD47 treatment leads to enhanced tumor cell phagocytosis by both M1 and M2 macrophage subtypes with a higher phagocytosis rate by M1 macrophages. Furthermore, these data demonstrate that anti-CD47 treatment alone can shift the phenotype of macrophages toward the M1 subtype in vivo.

  9. Anti-CD47 Treatment Stimulates Phagocytosis of Glioblastoma by M1 and M2 Polarized Macrophages and Promotes M1 Polarized Macrophages In Vivo

    Science.gov (United States)

    Kahn, Suzana A.; Azad, Tej D.; Gholamin, Sharareh; Xu, Chelsea Y.; Liu, Jie; Achrol, Achal S.; Richard, Chase; Sommerkamp, Pia; Schoen, Matthew Kenneth; McCracken, Melissa N.; Majeti, Ravi; Weissman, Irving; Mitra, Siddhartha S.; Cheshier, Samuel H.

    2016-01-01

    Tumor-associated macrophages (TAMs) represent an important cellular subset within the glioblastoma (WHO grade IV) microenvironment and are a potential therapeutic target. TAMs display a continuum of different polarization states between antitumorigenic M1 and protumorigenic M2 phenotypes, with a lower M1/M2 ratio correlating with worse prognosis. Here, we investigated the effect of macrophage polarization on anti-CD47 antibody-mediated phagocytosis of human glioblastoma cells in vitro, as well as the effect of anti-CD47 on the distribution of M1 versus M2 macrophages within human glioblastoma cells grown in mouse xenografts. Bone marrow-derived mouse macrophages and peripheral blood-derived human macrophages were polarized in vitro toward M1 or M2 phenotypes and verified by flow cytometry. Primary human glioblastoma cell lines were offered as targets to mouse and human M1 or M2 polarized macrophages in vitro. The addition of an anti-CD47 monoclonal antibody led to enhanced tumor-cell phagocytosis by mouse and human M1 and M2 macrophages. In both cases, the anti-CD47-induced phagocytosis by M1 was more prominent than that for M2. Dissected tumors from human glioblastoma xenografted within NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ mice and treated with anti-CD47 showed a significant increase of M1 macrophages within the tumor. These data show that anti-CD47 treatment leads to enhanced tumor cell phagocytosis by both M1 and M2 macrophage subtypes with a higher phagocytosis rate by M1 macrophages. Furthermore, these data demonstrate that anti-CD47 treatment alone can shift the phenotype of macrophages toward the M1 subtype in vivo. PMID:27092773

  10. 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

  11. Association between CYP1A1m1 gene polymorphism and primary open-angle glaucoma.

    Science.gov (United States)

    Costa, N B; Silva, C T X; Frare, A B; Silva, R E; Moura, K K V O

    2014-12-04

    The CYP1A1 gene is related to the generation of secondary metabolites that are capable of inducing DNA damage. The CYP1A1m1 polymorphism has been examined in many studies, and is located in a region near loci that have been linked to glaucoma, including the locus GLC1I. As a result, this polymorphism has been related to several diseases that are influenced by exposure to xenobiotic as well as primary open-angle glaucoma. We compared the prevalence of the CYP1A1m1 polymorphism in 152 Brazilian patients, 100 patients with primary open-angle glaucoma, and 52 normal controls using restriction fragment length polymorphism analysis. The frequency of the homozygous wild-type (w1/w1) CYP1A1 gene among patients with primary open-angle glaucoma (N = 100) was 16%, for genotype w1/m1, the frequency was 77%, and for m1/m1 it was 7%. Among the control group (N = 52), the frequency of the homozygous wild-type (w1/w1) CYP1A1 gene was 54%, the frequency of w1/m1 was 46%, and the frequency of m1/m1 was 0%. The presence of the CYP1A1m1 polymorphism may interfere with xenobiotic metabolism and exacerbate direct or indirect damage to the optic nerve. These CYP1A1m1 polymorphisms may be risk factors for primary open-angle glaucoma.

  12. La utilización de la gestión del conocimiento y la toma de decisiones en el área de proceso monitoreo y control de proyecto (PMC de CMMI

    Directory of Open Access Journals (Sweden)

    Carlos Molina Villalobos

    2011-11-01

    Full Text Available En el siglo XXI se evidencia un elevado interés en la gestión del conocimiento, incluso forma parte de las estrategias utilizadas en la administración de los recursos intangibles con el objetivo de alcanzar ventajas competitivas. La gestión del conocimiento y la gestión de la calidad constituyen áreas imprescindibles para el crecimiento y la mejora económica de la organización. La inexistencia de la gestión de la calidad en las empresas dedicadas al software, el crecimiento de los presupuestos y los atrasos en las entregas pactadas, son algunos de los problemas que existían en el desarrollo del software hasta el surgimiento de Capability Madurity Model Integration, modelo que enseña cuál es el camino a seguir para alcanzar determinado nivel de madurez de la propia organización o de determinadas áreas de procesos. Una de las áreas de procesos de Capability Madurity Model Integration es PMC, que se encarga de la toma de acciones correctivas en presencia de determinadas desviaciones de la planificación. La toma de decisiones inteligentes, a partir de una buena gestión del conocimiento, para la ejecución de acciones correctivas del PMC, contribuye a que estas acciones sean eficientes y generen solo los costos necesarios en dependencia de la magnitud de la desviación analizada.

  13. SAR studies on carboxylic acid series M(1) selective positive allosteric modulators (PAMs).

    Science.gov (United States)

    Kuduk, Scott D; Beshore, Douglas C

    2014-01-01

    There is mounting evidence from preclinical and early proof-of-concept studies suggesting that selective modulation of the M1 muscarinic receptor is efficacious in cognitive models of Alzheimer's disease (AD). A number of nonselective M1 muscarinic agonists have previously shown positive effects on cognitive function in AD patients, but were limited due to cholinergic adverse events thought to be mediated by pan activation of the M2 to M5 sub-types. Thus, there is a need to identify selective activators of the M1 receptor to evaluate their potential in cognitive disorders. One strategy to confer selectivity for M1 is the identification of allosteric agonists or positive allosteric modulators, which would target an allosteric site on the M1 receptor rather than the highly conserved orthosteric acetylcholine binding site. BQCA has been identified as a highly selective carboxylic acid M1 PAM and this review focuses on an extensive lead optimization campaign undertaken on this compound.

  14. M1 Protein Allows Group A Streptococcal Survival in Phagocyte Extracellular Traps through Cathelicidin Inhibition

    OpenAIRE

    Lauth, Xavier; von Köckritz-Blickwede, Maren; McNamara, Case W; Myskowski, Sandra; Zinkernagel, Annelies S.; Beall, Bernard; Ghosh, Partho; Richard L Gallo; Nizet, Victor

    2009-01-01

    M1 protein contributes to Group A Streptococcus (GAS) systemic virulence by interfering with phagocytosis and through proinflammatory activities when released from the cell surface. Here we identify a novel role of M1 protein in the stimulation of neutrophil and mast cell extracellular trap formation, yet also subsequent survival of the pathogen within these DNA-based innate defense structures. Targeted mutagenesis and heterologous expression studies demonstrate M1 protein promotes resistance...

  15. Non-viral FoxM1 gene delivery to hepatocytes enhances liver repopulation.

    Science.gov (United States)

    Xiang, D; Liu, C-C; Wang, M-J; Li, J-X; Chen, F; Yao, H; Yu, B; Lu, L; Borjigin, U; Chen, Y-X; Zhong, L; Wangensteen, K J; He, Z-Y; Wang, X; Hu, Y-P

    2014-05-22

    Hepatocyte transplantation as a substitute strategy of orthotopic liver transplantation is being studied for treating end-stage liver diseases. Several technical hurdles must be overcome in order to achieve the therapeutic liver repopulation, such as the problem of insufficient expansion of the transplanted hepatocytes in recipient livers. In this study, we analyzed the application of FoxM1, a cell-cycle regulator, to enhance the proliferation capacity of hepatocytes. The non-viral sleeping beauty (SB) transposon vector carrying FoxM1 gene was constructed for delivering FoxM1 into the hepatocytes. The proliferation capacities of hepatocytes with FoxM1 expression were examined both in vivo and in vitro. Results indicated that the hepatocytes with FoxM1 expression had a higher proliferation rate than wild-type (WT) hepatocytes in vitro. In comparison with WT hepatocytes, the hepatocytes with FoxM1 expression had an enhanced level of liver repopulation in the recipient livers at both sub-acute injury (fumaryl acetoacetate hydrolase (Fah)(-/-) mice model) and acute injury (2/3 partial hepatectomy mice model). Importantly, there was no increased risk of tumorigenicity with FoxM1 expression in recipients even after serial transplantation. In conclusion, expression of FoxM1 in hepatocytes enhanced the capacity of liver repopulation without inducing tumorigenesis. FoxM1 gene delivered by non-viral SB vector into hepatocytes may be a viable approach to promote therapeutic repopulation after hepatocyte transplantation.

  16. Monocyte Differentiation towards Protumor Activity Does Not Correlate with M1 or M2 Phenotypes

    Directory of Open Access Journals (Sweden)

    G. Karina Chimal-Ramírez

    2016-01-01

    Full Text Available Macrophages facilitate breast cancer progression. Macrophages were initially classified as M1 or M2 based on their distinct metabolic programs and then expanded to include antitumoral (M1 and protumoral (M2 activities. However, it is still uncertain what markers define the pro- and antitumoral phenotypes and what conditions lead to their formation. In this study, monocytic cell lines and primary monocytes were subjected to commonly reported protocols of M1/M2 polarization and conditions known to engage monocytes into protumoral functions. The results showed that only IDO enzyme and CD86 M1 markers were upregulated correlating with M1 polarization. TNF-α, CCR7, IL-10, arginase I, CD36, and CD163 were expressed indistinguishably from M1 or M2 polarization. Similarly, protumoral engaging resulted in upregulation of both M1 and M2 markers, with conditioned media from the most aggressive breast cancer cell line promoting the greatest changes. In spite of the mixed phenotype, M1-polarized macrophages exhibited the highest expression/secretion of inflammatory mediators, many of which have previously been associated with breast cancer aggressiveness. These data argue that although the existence of protumoral macrophages is unquestionable, their associated phenotypes and the precise conditions driving their formation are still unclear, and those conditions may need both M1 and M2 stimuli.

  17. Monocyte Differentiation towards Protumor Activity Does Not Correlate with M1 or M2 Phenotypes

    Science.gov (United States)

    Chimal-Ramírez, G. Karina; Espinoza-Sánchez, Nancy Adriana; Chávez-Sánchez, Luis; Arriaga-Pizano, Lourdes

    2016-01-01

    Macrophages facilitate breast cancer progression. Macrophages were initially classified as M1 or M2 based on their distinct metabolic programs and then expanded to include antitumoral (M1) and protumoral (M2) activities. However, it is still uncertain what markers define the pro- and antitumoral phenotypes and what conditions lead to their formation. In this study, monocytic cell lines and primary monocytes were subjected to commonly reported protocols of M1/M2 polarization and conditions known to engage monocytes into protumoral functions. The results showed that only IDO enzyme and CD86 M1 markers were upregulated correlating with M1 polarization. TNF-α, CCR7, IL-10, arginase I, CD36, and CD163 were expressed indistinguishably from M1 or M2 polarization. Similarly, protumoral engaging resulted in upregulation of both M1 and M2 markers, with conditioned media from the most aggressive breast cancer cell line promoting the greatest changes. In spite of the mixed phenotype, M1-polarized macrophages exhibited the highest expression/secretion of inflammatory mediators, many of which have previously been associated with breast cancer aggressiveness. These data argue that although the existence of protumoral macrophages is unquestionable, their associated phenotypes and the precise conditions driving their formation are still unclear, and those conditions may need both M1 and M2 stimuli. PMID:27376091

  18. PMC Control Design Principle and Program Implementation of Auxiliary Function M Commands in CNC Machine Tool Based on FANUC Oi Mate-MD System%基于FANUC Oi Mate-MD 系统的数控辅助功能M指令的PMC控制设计原理和程序实现

    Institute of Scientific and Technical Information of China (English)

    呼刚义; 杨新刚; 杨鹏

    2013-01-01

    数控机床辅助功能指令由CNC和PMC共同处理,但其具体运算处理过程国内还未见文献系统报道。用一具体实例对冷却液M指令的运行机制、PMC程序设计及加载、辅助功能M指令机床验证进行了详细阐述,有助于更好地使用、维护机床和利用系统提供的PMC梯形图来快速诊断故障,特别是对理解PMC程序、扩展开发机床控制功能提供了参考。%CNC machine tool auxiliary function commands are handled by CNC and PMC,but their concrete operation processes have not been reported in domestic literature system. Based on the specific examples,the operation mechanism of coolant M instruc-tion,the design and load of PMC program,the auxiliary function commands machine validation,were elaborated in detail. This will contribute to a better use and maintenance,and using PMC ladder diagram interface of NC system to diagnose fault quickly,especially it provides reference for understanding the PMC program,extending the development of machine control function.

  19. Experimental Conditions: SE37_S19_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available opes SE37_S19 PSEUDO: Unlabeled and labeled Medicago samples for flavonoid annotation using ShiftedIonsFinde...03_M1) and for a blank sample (S16_M1 to S16_M3) are used. Import file name is unlabeling SE37_DS5 Flavonoid like peak search by ShiftedIonsFinder ...

  20. Radioiodinated ganglioside G/sub M1/: A potential tracer for neurological studies

    Energy Technology Data Exchange (ETDEWEB)

    Zalutsky, M.R.; Gallagher, P.; Magistretti, P.L.; Ghidoni, R.

    1985-05-01

    Ganglioside G/sub M1/ is a glycosphingolipid which appears to be involved in the regeneration of damaged neuronal tissue. In addition, it is being investigated clinically in the treatment of various neuropathies. If labeled with the appropriate isotope, G/sub M1/ might be useful as a probe of these processes, particularly if it accumulates preferentially in cerebral infarcts. The G/sub M1/ -tyr derivative was labeled with I-125 in 75% yield using the Iodogen method and at micellar concentration was isolated using gel chromatography. Binding of I-125 (G/sub M1/ -tyr) to rat neuronal membranes was measured at concentrations of 5,50, and 500 nM. The amount bound (8,26, and 158 pmol/gm membrane) was similar to that reported for H-3(G/sub M1/). The biodistribution of I-125(G/sub M1/ -tyr) in mice at both micellar and monomeric concentrations was also similar to that of H-3(G/sub M1/). However, at monomeric concentrations, thyroid uptake of I-125 was about 10 times higher than at micellar concentrations, suggesting differential dehalogenation of the two forms. Initial studies in the gerbil stroke model suggest that the uptake of I-125(G/sub M1/ -tyr) in damaged brain is twice that in normal tissue.

  1. CONDITIONAL INVOLVEMENT OF MUSCARINIC M(1) RECEPTORS IN VAGALLY MEDIATED CONTRACTION OF GUINEA-PIG BRONCHI

    NARCIS (Netherlands)

    TENBERGE, REJ; ROFFEL, AF; ZAAGSMA, J

    The involvement of ganglionic muscarinic M(1) receptors in vagally induced bronchoconstriction in guinea-pig airways is controversial. Therefore, we studied the effects of the M(1)-selective muscarinic receptor antagonist pirenzepine on vagus nerve (VNS, preganglionic) and electrical field

  2. A note on predicting recessions in the euro area using real M1

    OpenAIRE

    Jens Boysen-Hogrefe

    2012-01-01

    Real M1 is a renowned leading indicator used to forecast real economic activity. This note provides evidence that real M1 is also a suitable recession indicator that gave a clear and early signal for the Great Recession as long as changes in money demand are controlled for.

  3. Analytical Method (M): SE37_S18_M1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available SE37_S18_M1 This is a pseudo metadata prepared for integrated analyses of multiple ...datasets. The raw data obtained from LC-Orbitarp MS analyses for Medicago samples and a blank sample (S17_M1

  4. 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,...

  5. Experimental Conditions: SE19_S2_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available SE19_S2_M1_D1 SE19 Grobal triacylglycerol analysis in mouse liver and white adipose... tissue (WAT) by high resolution LC/ESI-QTOF MS/MS SE19_S2 Mouse white adipose tissue (WAT) SE19_S2_M1 20 ug

  6. FoxM1 is required for execution of the mitotic programme and chromosome stability

    NARCIS (Netherlands)

    Laoukili, J.; Kooistra, M.R.H.; Brás, A.; Kauw, J.; Kerkhoven, R.M.; Morrison, A.; Clevers, H.C.; Medema, R.H.

    2005-01-01

    Transcriptional induction of cell-cycle regulatory proteins ensures proper timing of subsequent cell-cycle events. Here we show that the Forkhead transcription factor FoxM1 regulates expression of many G2-specific genes and is essential for chromosome stability. Loss of FoxM1 leads to pleiotropic ce

  7. FoxM1 is required for execution of the mitotic programme and chromosome stability.

    NARCIS (Netherlands)

    Laoukili, J.; Kooistra, M.R.H.; Bras, A.; Kauw, J.; Kerkhoven, R.M.; Morrison, A.; Clevers, J.C.; Medema, R.H.

    2005-01-01

    Transcriptional induction of cell-cycle regulatory proteins ensures proper timing of subsequent cell-cycle events. Here we show that the Forkhead transcription factor FoxM1 regulates expression of many G2-specific genes and is essential for chromosome stability. Loss of FoxM1 leads to pleiotropic ce

  8. 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

  9. Regional distribution of M1, M2 and non-M1, non-M2 subtypes of muscarinic binding sites in rat brain

    Energy Technology Data Exchange (ETDEWEB)

    Ehlert, F.J.; Tran, L.P. (Univ. of California, Irvine (USA))

    1990-12-01

    The distribution of subtypes of the muscarinic receptor in homogenates of the rat brain was investigated by measuring the competitive inhibition of the binding (3H)N-methylscopolamine by pirenzepine and AF-DX 116 (11((2-((diethylamino)methyl)-1-piperidinyl)acetyl)-5, 11-dihydro-6H-pyrido(2,3-b)(1,4)benzodiazepine-6-one). In most brain regions, the competitive binding curves for AF-DX 116 and pirenzepine were consistent with a two-site model. The dissociation constant of pirenzepine for its high-affinity site (M1 receptor) was approximately 10(-8) M, whereas the dissociation constant of AF-DX 116 for its high affinity site (M2 receptor) was approximately 10(-7) M. In many regions, particularly those in the forebrain, the sum of the densities of the M1 and M2 binding sites was substantially less than 100% of the total sites, indicating the existence of a third population of sites lacking high affinity for both pirenzepine and AF-DX 116. We have designated these latter sites as non-M1, non-M2 muscarinic receptors. In general, the densities of the M1 and non-M1, non-M2 binding sites were highest in cerebral cortex, corpus striatum and hippocampus, intermediate in thalamus and hypothalamus, and lowest in midbrain, medulla-pons and cerebellum, whereas the M2 binding site had a relatively low, uniform density throughout the brain. The binding capacity of (3H)N-methylquinuclidinyl benzilate was estimated to be 20 to 30% lower than that of (3H)quinuclidinyl benzilate in various regions of the forebrain, but not in more caudal regions of the brain where the two radioligands had approximately the same binding capacities.

  10. The luminosity function of cluster galaxies relations among M$_{1}$, M* and the morphological type

    CERN Document Server

    Trevese, D; Appodia, B

    1996-01-01

    A study of the luminosity function of 36 Abell clusters of galaxies has been carried out using photographic plates obtained with the Palomar 1.2 m Schmidt telescope. The relation between the magnitude M_1 of the brightest cluster member and the Schechter function parameter M* has been analyzed. A positive correlation between M* and M_1 is found. However clusters appear segregated in the M_1-M* plane according to their Rood & Sastry class in such a way that on average M_1 becomes brighter while M* becomes fainter going from late to early Rood & Sastry and also Bautz & Morgan classes. Also a partial correlation analysis involving the magnitude M_10 of the 10th brightest galaxy, shows a negative intrinsic correlation between M_1 and M*. These results agree with the cannibalism model for the formation of brightest cluster members, and provide new constraints for theories of cluster formation and evolution.

  11. 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.

  12. Exploration of FoxM1 and downstream related target molecule expression in cervical cancer tissue

    Institute of Scientific and Technical Information of China (English)

    Yi-Chong Yuan; QiongYang

    2016-01-01

    Objective:To study the expression of FoxM1 and downstream related target molecules in cervical cancer tissue.Methods:Cervical cancer tissue and normal cervical tissue were collected to detect the expression of FoxM1, proliferation-related genes (CDK6 and CDK8) and angiogenesis-related genes (VEGFA, VEGFB and VEGFC); Hela cells were cultured and transfected with FoxM1 siRNA, and then expression of CDK6, CDK8, VEGFA, VEGFB and VEGFC were detected.Results:mRNA contents of FoxM1, CDK6, CDK8, VEGFA, VEGFB and VEGFC in cervical cancer tissue were significantly higher than those in normal cervical tissue; mRNA content of FoxM1 was positively correlated with mRNA contents of CDK6, CDK8, VEGFA, VEGFB and VEGFC; mRNA contents of CDK6, CDK8, VEGFA, VEGFB and VEGFC of FoxM1-siRNA group were significantly lower than those of negative control-siRNA group.Conclusion:FoxM1 expression abnormally increases in cervical cancer tissue, and its downstream target genes include CDK6, CDK8, VEGFA, VEGFB and VEGFC.

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

    CERN Document Server

    Sepehri, Alireza; 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 this model could explain the oscillation of universe between contraction and expansion branches? We try to address this issue in the framework of 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 removes these states, $M1$...

  14. Enzyme-linked immunosorbent assay for determination of aflatoxin M1 based on magnetic nanoparticles

    Science.gov (United States)

    Atanasova, M. K.; Ivanova, N. V.; Godjevargova, T. I.

    2017-02-01

    A sensitive enzyme immunoassay with magnetic nanoparticles (Method A) for the quantitative determination of aflatoxin M1 in milk was developed. This immunoassay was based on the immobilization of monoclonal antibody (mAb) on the modified magnetic nanoparticles (MNPs-NH2). It was observed that for each mg of the MNPs, 25 µg of antibody was immobilized. Both aflatoxin M1 in the sample and aflatoxin M1-BSA-peroxidase conjugate competed for the immobilized antibody. The proposed Method A was compared with other method (B). The Method B was based on the immobilization of aflatoxin M1-BSA conjugate on the MNPs-NH2, which competed with the aflatoxin M1 in the sample for binding to the added mAb. The binding of mAb to the aflatoxin M1-BSA-MNPs-NH2 was detected using a target secondary IgG-peroxidase antibody. The analytical characteristics of the two methods were compared. Real milk samples were investigated for present of aflatoxin M1. Two methods were based on the use of MNPs as a solid support for covalently immunoreagents immobilization. A comfortable separation of bound and free fraction of the tracer can be performed only through a simple collection of the MNPs by a permanent magnet. The application of MNPs helps to eliminate non-specific binding and to retain higher activity of bound biomolecules. The development of a MNPs-based ELISA for determination of aflatoxin M1 has a great potential to supersede the traditional ELISA for aflatoxin M1 diagnosis.

  15. Bounds on Subspace Codes Based on Subspaces of Type (m,1 in Singular Linear Space

    Directory of Open Access Journals (Sweden)

    You Gao

    2014-01-01

    Full Text Available The Sphere-packing bound, Singleton bound, Wang-Xing-Safavi-Naini bound, Johnson bound, and Gilbert-Varshamov bound on the subspace codes n+l,M,d,(m,1q based on subspaces of type (m,1 in singular linear space Fq(n+l over finite fields Fq are presented. Then, we prove that codes based on subspaces of type (m,1 in singular linear space attain the Wang-Xing-Safavi-Naini bound if and only if they are certain Steiner structures in Fq(n+l.

  16. Locations of All Shotpoints, USGS Cruise M1-98-GM (GOM98SHTALLG.SHP)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — All shotpoint locations from multichannel seismics survey, USGS cruise M1-98-GM. During June 1998 and April 1999, the U.S. Geological Survey (USGS) conducted two...

  17. Aflatoxin M1 levels in raw milk, pasteurized milk and infant formula

    National Research Council Canada - National Science Library

    Omar, Sharaf Shareef

    2016-01-01

    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...

  18. 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

  19. 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.

  20. Coiled-Coil Irregularities and Instabilities in Group A Streptococcus M1 Are Required for Virulence

    Energy Technology Data Exchange (ETDEWEB)

    McNamara, Case; Zinkernagel, Annelies S.; Macheboeuf, Pauline; Cunningham, Madeleine W.; Nizet, Victor; Ghosh, Partho (UO-HSC); (UCSD)

    2008-07-21

    Antigenically variable M proteins are major virulence factors and immunogens of the human pathogen group A Streptococcus (GAS). Here, we report the -3 angstrom resolution structure of a GAS M1 fragment containing the regions responsible for eliciting type-specific, protective immunity and for binding fibrinogen, which promotes M1 proinflammatory and antiphagocytic functions. The structure revealed substantial irregularities and instabilities throughout the coiled coil of the M1 fragment. Similar structural irregularities occur in myosin and tropomyosin, explaining the patterns of cross-reactivity seen in autoimmune sequelae of GAS infection. Sequence idealization of a large segment of the M1 coiled coil enhanced stability but diminished fibrinogen binding, proinflammatory effects, and antibody cross-reactivity, whereas it left protective immunogenicity undiminished. Idealized M proteins appear to have promise as vaccine immunogens.

  1. Presence of Aflatoxin M1 in Raw Milk for Human Consumption in Palestinian

    Directory of Open Access Journals (Sweden)

    Ibrahim Mahmoud AL ZUHEIR

    2012-09-01

    Full Text Available The absences or insufficient food control program result in the occurrence of mycotoxin in milk and milk products, which poses a serious risk for humans and can be a public health concern. This study was conducted to highlight the occurrence of aflatoxin M1 in Palestine raw milk collected at farms from Tulkarm, Nablus and Jenin. Aflatoxin M1 was determined by direct competitive ELISA technique. 85 % (34 of 40 of the total examined raw milk samples tested were positive. The aflatoxin M1 contamination levels were between 3 - 80 ppt with a mean of 29.57 ppt. There was a high incidence rate with 92 % (11 of 12 and the highest means of contaminated with aflatoxin M1 in the samples tested in Tulkarm city (P ≤ 0.05. 20 % of the analyzed samples (8 of 40 exceeded the maximum permissible limit (50 ppt in European Codex, with a range of 2 - 80 ppt.

  2. FoxM1 mediated resistance to gefitinib in non-small-cell lung cancer cells

    Institute of Scientific and Technical Information of China (English)

    Nuo XU; Xin ZHANG; Xun WANG; Hai-yan GE; Xiao-ying WANG; David GARFIELD; Ping YANG; Yuan-lin SONG; Chun-xue BAI

    2012-01-01

    Gefitinib is effective in only approximately 20% of patients with non-small-cell lung cancer (NSCLC),and the underlying mechanism remains unclear.FoxM1 is upregulated in NSCLC and associated with a poor prognosis in NSCLC patients.In this study,we examined the possible role of FoxM1 in gefitinib resistance and the related mechanisms.Methods:Gefitinib resistant human lung adenocarcinoma cell line SPC-A-1 and gefitinib-sensitive human lung mucoepidermoid carcinoma cell line NCI-H292 were used.mRNA and protein expression of FoxM1 and other factors were tested with quantitative RT PCR and Western blot analysis.RNA interference was performed to suppress FoxM1 expression in SPC-A-1 cells,and lentiviral infection was used to overexpress FoxM1 in H292 cells.MTT assay and flow cytometry were used to examine the proliferation and apoptosis of the cells.Results:Treatment of SPC-A-1 cells with gefitinib (1 and 10 μmol/L) upregulated the expression of FoxM1 in time- and concentrationdependent manners,while gefrtinib (1 μmol/L) downregulated in H292 cells.In SPC-A-1 cells treated with gefitinib (1 μmol/L),the expression of several downstream targets of FoxM1,including survivin,cyclin B1,SKP2,PLK1,Aurora B kinase and CDC25B,were significantly upregulated.Overexpression of FoxM1 increased the resistance in H292 cells,while attenuated FoxM1 expression restored the sensitivity to gefitinib in SPC-A-1 cells by inhibiting proliferation and inducing apoptosis.Conclusion:The results suggest that FoxM1 plays an important role in the resistance of NSCLC cells to gefitinib in vitro.FoxM1 could be used as a therapeutic target to overcome the resistance to gefitinib.

  3. q-differential operator representation of the quantum superalgebra Uq(sl(M+1|N+1))

    CERN Document Server

    Kimura, K

    1996-01-01

    A representation of the quantum superalgebra Uq(sl(M+1|N+1)) is constructed based on the q-differential operators acting on the coherent states parameterized by coordinates. These coordinates correspond to the local ones of the flag manifold. This realization provides us with a guide to construct the free field realization for the quantum affine superalgebra Uq^(sl(M+1|N+1)) at arbitrary level.

  4. 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.

  5. 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.

  6. 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.

  7. 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.)

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

    Science.gov (United States)

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

    2016-05-01

    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.

  9. 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.

  10. Optical illusion alters M1 excitability after mirror therapy: a TMS study.

    Science.gov (United States)

    Läppchen, C H; Ringer, T; Blessin, J; Seidel, G; Grieshammer, S; Lange, R; Hamzei, F

    2012-11-01

    The contralesional primary motor cortex (M1) has been suggested to be involved in the motor recovery after mirror therapy, but whether the ipsilesional M1 is influenced by the contralesional M1 via transcallosal interhemispheric inhibition (IHI) is still unclear. The present study investigated the change of IHI as well as the intracortical inhibition and intracortical facilitation of both M1 induced by training in a mirror with the use of transcranial magnetic stimulation (TMS). In this 2 × 2 factorial design (time × group), healthy subjects exercised standardized motor skills with their right hand on four consecutive days. Either a mirror (mirror group) or a board (control group) was positioned between their hands. Before and after training TMS was applied along with training tests of both hands. Tests were the same motor skills exercised daily by both groups. Tests of the untrained left hand improved significantly more in the mirror group than in the control group after training (P = 0.02) and showed a close correlation with an increase of intracortical inhibition of M1(left). IHI did not show any difference between investigation time points and groups. The present study confirms the previous suggestion of the involvement of the "contralesional" left-side (ipsilateral to the hand behind the mirror) M1 after mirror therapy, which is not mediated by IHI. Even with the same motor skill training (both groups performed same motor skills) but with different visual information, different networks are involved in training-induced plasticity.

  11. Differential Roles of M1 and M2 Microglia in Neurodegenerative Diseases.

    Science.gov (United States)

    Tang, Yu; Le, Weidong

    2016-03-01

    One of the most striking hallmarks shared by various neurodegenerative diseases, including Parkinson's disease, Alzheimer's disease (AD), and amyotrophic lateral sclerosis, is microglia-mediated neuroinflammation. Increasing evidence indicates that microglial activation in the central nervous system is heterogeneous, which can be categorized into two opposite types: M1 phenotype and M2 phenotype. Depending on the phenotypes activated, microglia can produce either cytotoxic or neuroprotective effects. In this review, we focus on the potential role of M1 and M2 microglia and the dynamic changes of M1/M2 phenotypes that are critically associated with the neurodegenerative diseases. Generally, M1 microglia predominate at the injury site at the end stage of disease, when the immunoresolution and repair process of M2 microglia are dampened. This phenotype transformation is very complicated in AD due to the phagocytosis of regionally distributed β-amyloid (Aβ) plaque and tangles that are released into the extracellular space. The endogenous stimuli including aggregated α-synuclein, mutated superoxide dismutase, Aβ, and tau oligomers exist in the milieu that may persistently activate M1 pro-inflammatory responses and finally lead to irreversible neuron loss. The changes of microglial phenotypes depend on the disease stages and severity; mastering the stage-specific switching of M1/M2 phenotypes within appropriate time windows may provide better therapeutic benefit.

  12. The Plasmodium falciparum malaria M1 alanyl aminopeptidase (PfA-M1: insights of catalytic mechanism and function from MD simulations.

    Directory of Open Access Journals (Sweden)

    Peter M Jones

    Full Text Available Malaria caused by several species of Plasmodium is major parasitic disease of humans, causing 1-3 million deaths worldwide annually. The widespread resistance of the human parasite to current drug therapies is of major concern making the identification of new drug targets urgent. While the parasite grows and multiplies inside the host erythrocyte it degrades the host cell hemoglobin and utilizes the released amino acids to synthesize its own proteins. The P. falciparum malarial M1 alanyl-aminopeptidase (PfA-M1 is an enzyme involved in the terminal stages of hemoglobin digestion and the generation of an amino acid pool within the parasite. The enzyme has been validated as a potential drug target since inhibitors of the enzyme block parasite growth in vitro and in vivo. In order to gain further understanding of this enzyme, molecular dynamics simulations using data from a recent crystal structure of PfA-M1 were performed. The results elucidate the pentahedral coordination of the catalytic Zn in these metallo-proteases and provide new insights into the roles of this cation and important active site residues in ligand binding and in the hydrolysis of the peptide bond. Based on the data, we propose a two-step catalytic mechanism, in which the conformation of the active site is altered between the Michaelis complex and the transition state. In addition, the simulations identify global changes in the protein in which conformational transitions in the catalytic domain are transmitted at the opening of the N-terminal 8 Å-long channel and at the opening of the 30 Å-long C-terminal internal chamber that facilitates entry of peptides to the active site and exit of released amino acids. The possible implications of these global changes with regard to enzyme function are discussed.

  13. M1 contributes to the intrinsic but not the extrinsic components of motor-skills.

    Science.gov (United States)

    Romei, Vincenzo; Thut, Gregor; Ramos-Estebanez, Ciro; Pascual-Leone, Alvaro

    2009-10-01

    Procedural skills consist of several components that can be simultaneously acquired. During a motor-learning task we can distinguish between how a "movement" is performed (intrinsic component) and the spatial-related (extrinsic) component of this movement. The intrinsic movement component is thought to be supported by motor loops, including primary motor cortex (M1) as assessed with neuroimaging studies. Here we want to test further whether M1 makes a critical contribution to the movement rather than spatial-related component of skill-learning. To this purpose, we used repetitive Transcranial Magnetic Stimulation (rTMS) and the serial reaction time (SRT) task. Twenty right-handed participants performed the SRT-task starting with their left or right hand. After this learning session, participants switched to the untrained hand by performing original (spatial-related) and mirror-ordered (movement-based) sequences. rTMS was applied to M1 ipsi- or contralateral to the transfer-hand and both sequences were retested. Results revealed rTMS-interference with motor-skill transfer of mirror-ordered but not original sequences, showing that M1 is critically involved in the retrieval/transformation of the intrinsic but not the extrinsic movement coordinates. rTMS-interference in the mirror-condition consisted of both (i) disruption and (ii) release of motor-skill transfer depending on the stimulated hemisphere and on transfer-hand. The pattern of results suggests (i) contralateral (right) M1 involvement in retrieval/transformation of motor information during left-hand reproduction of previously acquired right-hand motor-skills; and (ii) modulatory interactions of inhibitory nature from the dominant (left) to the non-dominant (right) M1 in the same transfer-condition. These results provide further evidence that M1 is essential to intrinsic movement-based skill-learning and novel insight on models of motor-learning and hemispheric specialization, suggesting the involvement of

  14. Neoglycolipid analogues of ganglioside G sub M1 as functional receptors of cholera toxin

    Energy Technology Data Exchange (ETDEWEB)

    Pacuszka, T.; Bradley, R.M.; Fishman, P.H. (National Inst. of Health, Bethesda, MD (United States))

    1991-03-12

    The authors synthesized several lipid analogues of ganglioside G{sub M1} by attaching its oligosaccharide moiety (G{sub M1}OS) to aminophospholipids, aliphatic amines, and cholesteryl hemisuccinate. They incubated G{sub M1}-deficient rat glioma C6 cells with each of the derivatives as well as native G{sub M1} and assayed the cells for their ability to bind and respond to cholera toxin. On the basis of the observed increase in binding of {sup 125}I-labeled cholera toxin, it was apparent that the cells took up and initially incorporated most of the derivatives into the plasma membrane. In the case of the aliphatic amine derivatives, the ability to generate new toxin binding sites was dependent on chain length; whereas the C{sub 10} derivative was ineffective, C{sub 12} and higher analogues were effective. Increased binding was dependent on both the concentration of the neoglycolipid in the medium and the time of exposure. Cells pretreated with the various derivatives accumulated cyclic AMP in response to cholera toxin, but there were differences in their effectiveness. The cholesterol and long-chain aliphatic amine derivatives were more effective than native G{sub M1}, whereas the phospholipid derivatives were less effective. The distance between G{sub M1}OS and the phospholipid also appeared to influence its functional activity. The results indicate that although G{sub M1}OS provides the recognition site for the binding of cholera toxin, the nature of the lipid moiety plays an important role in the action of the toxin.

  15. Curcumin retunes cholesterol transport homeostasis and inflammation response in M1 macrophage to prevent atherosclerosis.

    Science.gov (United States)

    Chen, Fang-Yuan; Zhou, Juan; Guo, Ning; Ma, Wang-Ge; Huang, Xin; Wang, Huan; Yuan, Zu-Yi

    2015-11-27

    Lipoprotein cholesterol metabolism dysfunction in the arterial wall is a major contributor to atherosclerosis, and excessive lipid intake and failed cholesterol homeostasis may accelerate the atherogenic process. Curcumin exerts multiple effects by alleviating inflammation, hyperlipidemia, and atherosclerosis; however, its role in cholesterol transport homeostasis and its underlying impact on inflammatory M1 macrophages are poorly understood. This work aimed to investigate the effect of curcumin on cholesterol transport, the inflammatory response and cell apoptosis in M1 macrophages. RAW264.7 macrophages (M0) were induced with LPS plus IFN-γ for 12 h to develop a M1 subtype and were then incubated with curcumin at different concentrations (6.25 and 12.5 μmol/L) in the presence or absence of oxLDL. Then, cholesterol influx/efflux and foam cell formation as well as inflammation and apoptosis were evaluated. It was found that curcumin increased cholesterol uptake measured by the Dil-oxLDL binding assay, and simultaneously increased cholesterol efflux carried out by Apo-A1 and HDL in M1 cells. Curcumin further reinforced ox-LDL-induced cholesterol esterification and foam cell formation as determined by Oil Red O and BODIPY staining. Moreover, curcumin dramatically reduced ox-LDL-induced cytokine production such as IL-1β, IL-6 as well as TNF-α and M1 cell apoptosis. We also found that curcumin upregulated CD36 and ABCA1 in M1 macrophages. Curcumin increased PPARγ expression, which in turn promoted CD36 and ABCA1 expression. In conclusion, curcumin may increase the ability of M1 macrophages to handle harmful lipids, thus promoting lipid processing, disposal and removal, which may support cholesterol homeostasis and exert an anti-atherosclerotic effect.

  16. Peroxiredoxin II promotes hepatic tumorigenesis through cooperation with Ras/Forkhead box M1 signaling pathway.

    Science.gov (United States)

    Park, Y-H; Kim, S-U; Kwon, T-H; Kim, J-M; Song, I-S; Shin, H-J; Lee, B-K; Bang, D-H; Lee, S-J; Lee, D-S; Chang, K-T; Kim, B-Y; Yu, D-Y

    2016-07-07

    The current study was carried out to define the involvement of Peroxiredoxin (Prx) II in progression of hepatocellular carcinoma (HCC) and the underlying molecular mechanism(s). Expression and function of Prx II in HCC was determined using H-ras(G12V)-transformed HCC cells (H-ras(G12V)-HCC cells) and the tumor livers from H-ras(G12V)-transgenic (Tg) mice and HCC patients. Prx II was upregulated in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg mouse tumor livers, the expression pattern of which highly similar to that of forkhead Box M1 (FoxM1). Moreover, either knockdown of FoxM1 or site-directed mutagenesis of FoxM1-binding site of Prx II promoter significantly reduced Prx II levels in H-ras(G12V)-HCC cells, indicating FoxM1 as a direct transcription factor of Prx II in HCC. Interestingly, the null mutation of Prx II markedly decreased the number and size of tumors in H-ras(G12V)-Tg livers. Consistent with this, knockdown of Prx II in H-ras(G12V)-HCC cells reduced the expression of cyclin D1, cell proliferation, anchorage-independent growth and tumor formation in athymic nude mice, whereas overexpression of Prx II increased or aggravated the tumor phenotypes. Importantly, the expression of Prx II was correlated with that of FoxM1 in HCC patients. The activation of extracellular signal-related kinase (ERK) pathway and the expression of FoxM1 and cyclin D1 were highly dependent on Prx II in H-ras(G12V)-HCC cells and H-ras(G12V)-Tg livers. Prx II is FoxM1-dependently-expressed antioxidant in HCC and function as an enhancer of Ras(G12V) oncogenic potential in hepatic tumorigenesis through activation of ERK/FoxM1/cyclin D1 cascade.

  17. Mice Lacking M1 and M3 Muscarinic Acetylcholine Receptors Have Impaired Odor Discrimination and Learning

    Science.gov (United States)

    Chan, Wilson; Singh, Sanmeet; Keshav, Taj; Dewan, Ramita; Eberly, Christian; Maurer, Robert; Nunez-Parra, Alexia; Araneda, Ricardo C.

    2017-01-01

    The cholinergic system has extensive projections to the olfactory bulb (OB) where it produces a state-dependent regulation of sensory gating. Previous work has shown a prominent role of muscarinic acetylcholine (ACh) receptors (mAChRs) in regulating the excitability of OB neurons, in particular the M1 receptor. Here, we examined the contribution of M1 and M3 mAChR subtypes to olfactory processing using mice with a genetic deletion of these receptors, the M1−/− and the M1/M3−/− knockout (KO) mice. Genetic ablation of the M1 and M3 mAChRs resulted in a significant deficit in odor discrimination of closely related molecules, including stereoisomers. However, the discrimination of dissimilar molecules, social odors (e.g., urine) and novel object recognition was not affected. In addition the KO mice showed impaired learning in an associative odor-learning task, learning to discriminate odors at a slower rate, indicating that both short and long-term memory is disrupted by mAChR dysfunction. Interestingly, the KO mice exhibited decreased olfactory neurogenesis at younger ages, a deficit that was not maintained in older animals. In older animals, the olfactory deficit could be restored by increasing the number of new born neurons integrated into the OB after exposing them to an olfactory enriched environment, suggesting that muscarinic modulation and adult neurogenesis could be two different mechanism used by the olfactory system to improve olfactory processing. PMID:28210219

  18. Dynamic Changes of Microglia/Macrophage M1 and M2 Polarization in Theiler's Murine Encephalomyelitis.

    Science.gov (United States)

    Herder, Vanessa; Iskandar, Cut Dahlia; Kegler, Kristel; Hansmann, Florian; Elmarabet, Suliman Ahmed; Khan, Muhammad Akram; Kalkuhl, Arno; Deschl, Ulrich; Baumgärtner, Wolfgang; Ulrich, Reiner; Beineke, Andreas

    2015-11-01

    Microglia and macrophages play a central role for demyelination in Theiler's murine encephalomyelitis (TME) virus infection, a commonly used infectious model for chronic-progressive multiple sclerosis. In order to determine the dynamic changes of microglia/macrophage polarization in TME, the spinal cord of Swiss Jim Lambert (SJL) mice was investigated by gene expression profiling and immunofluorescence. Virus persistence and demyelinating leukomyelitis were confirmed by immunohistochemistry and histology. Electron microscopy revealed continuous myelin loss together with abortive myelin repair during the late chronic infection phase indicative of incomplete remyelination. A total of 59 genes out of 151 M1- and M2-related genes were differentially expressed in TME virus-infected mice over the study period. The onset of virus-induced demyelination was associated with a dominating M1 polarization, while mounting M2 polarization of macrophages/microglia together with sustained prominent M1-related gene expression was present during the chronic-progressive phase. Molecular results were confirmed by immunofluorescence, showing an increased spinal cord accumulation of CD16/32(+) M1-, arginase-1(+) M2- and Ym1(+) M2-type cells associated with progressive demyelination. The present study provides a comprehensive database of M1-/M2-related gene expression involved in the initiation and progression of demyelination supporting the hypothesis that perpetuating interaction between virus and macrophages/microglia induces a vicious circle with persistent inflammation and impaired myelin repair in TME.

  19. Reverse phase liquid chromatographic determination and confirmation of aflatoxin M1 in cheese.

    Science.gov (United States)

    Hisada, K; Terada, H; Yamamoto, K; Tsubouchi, H; Sakabe, Y

    1984-01-01

    A systematic method is proposed for determination and confirmation of aflatoxin M1 in cheese by liquid chromatography (LC). A sample of cheese is extracted with chloroform, cleaned up on 2 silica gel columns followed by a Sep-Pak C18 cartridge, and chromatographed on a 5 microns octadecyl silica column with fluorometric detection. The sample extract or standard is treated with n-hexane-trifluoroacetic acid (TFA) (4 + 1) for 30 min at 40 degrees C. Analysis by LC with TFA-treatment of the extract provides quantitative data. Multiple assays of 5 samples of Gouda cheese spiked with aflatoxin M1 at levels of 0.5, 0.1, and 0.05 ng/g showed average recoveries of 93.2, 91.6, and 92.4%, with coefficients of variation of 2.63, 3.97, and 4.52%, respectively. Assay of 5 naturally contaminated cheeses resulted in 0.051-0.448 ng/g of aflatoxin M1. Limit of quantitation is about 0.01 ng/g. The identity of aflatoxin M1 is confirmed by treating aflatoxin M1 or the M2a derivative with TFA-methanol (or ethanol) (3 + 1). The TFA-methanol reaction products of M2a could be detected quantitatively.

  20. E1, M1, E2 transition energies and probabilities of W$^{54+}$ ions

    CERN Document Server

    Ding, Xiao-bin; Liu, Jia-xin; Koike, Fumihiro; Murakami, Izumi; Kato, Daiji; Sakaue, Hiroyuki A; Nakamura, Nobuyuki; Dong, Chen-zhong

    2016-01-01

    A comprehensive theoretical study of the E1, M1, E2 transitions of Ca-like tungsten ions is presented. Using multi-configuration Dirac-Fock (MCDF) method with a restricted active space treatment, the wavelengths and probabilities of the M1 and E2 transitions between the multiplets of the ground state configuration ([Ne]3s$^{2}$3p$^{6}$3d$^{2}$) and of the E1 transitions between [Ne]3s$^{2}$3p$^{5}$3d$^{3}$ and [Ne]3s$^{2}$3p$^{6}$3d$^{2}$ have been calculated. The results are in reasonable agreement with available experimental data. The present E1 and M1 calculations are compared with previous theoretical values. For E2 transitions, the importance of electron correlation from 3s and 3p orbitals is pointed out. Several strong E1 transitions are predicted, which have potential advantage for plasma diagnostics.

  1. M1 muscarinic acetylcholine receptor agonism alters sleep without affecting memory consolidation.

    Science.gov (United States)

    Nissen, Christoph; Power, Ann E; Nofzinger, Eric A; Feige, Bernd; Voderholzer, Ulrich; Kloepfer, Corinna; Waldheim, Bernhard; Radosa, Marc-Philipp; Berger, Mathias; Riemann, Dieter

    2006-11-01

    Preclinical studies have implicated cholinergic neurotransmission, specifically M1 muscarinic acetylcholine receptor (mAChR) activation, in sleep-associated memory consolidation. In the present study, we investigated the effects of administering the direct M1 mAChR agonist RS-86 on pre-post sleep memory consolidation. Twenty healthy human participants were tested in a declarative word-list task and a procedural mirror-tracing task. RS-86 significantly reduced rapid eye movement (REM) sleep latency and slow wave sleep (SWS) duration in comparison with placebo. Presleep acquisition and postsleep recall rates were within the expected ranges. However, recall rates in both tasks were almost identical for the RS-86 and placebo conditions. These results indicate that selective M1 mAChR activation in healthy humans has no clinically relevant effect on pre-post sleep consolidation of declarative or procedural memories at a dose that reduces REM sleep latency and SWS duration.

  2. 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

    Muscarinic cholinergic receptors modulate dopaminergic function in brain pathways thought to mediate cocaine's abuse-related effects. Here, we sought to confirm and extend in the mouse species findings that nonselective muscarinic receptor antagonists can enhance cocaine's discriminative stimulus....... More importantly, we tested the hypothesis that muscarinic receptor agonists with varied receptor subtype selectivity can blunt cocaine's discriminative stimulus and reinforcing effects; we hypothesized a critical role for the M(1) and/or M(4) receptor subtypes in this modulation. Mice were trained...... to discriminate cocaine from saline, or to self-administer intravenous cocaine chronically. The nonselective muscarinic antagonists scopolamine and methylscopolamine, the nonselective muscarinic agonists oxotremorine and pilocarpine, the M(1)/M(4)-preferring agonist xanomeline, the putative M(1)-selective agonist...

  3. Nonlinear {omega}*-stabilization of the m = 1 mode in tokamaks

    Energy Technology Data Exchange (ETDEWEB)

    Rogers, B. [Univ. of Maryland, College Park, MD (United States). Inst. for Plasma Research; Zakharov, L. [Princeton Univ., NJ (United States). Plasma Physics Lab.

    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 {omega}*{sub 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.

  4. M1 AFLATOXIN, TOTAL BACTERIAL COUNT AND SOMATIC CELL COUNT IN ORGANIC AND CONVENTIONAL MILK

    Directory of Open Access Journals (Sweden)

    M. Trevisani

    2009-09-01

    Full Text Available Comparative quality evaluation of organic and conventional milk produced in similar environmental condition was performed. Bulk-tank milk was sampled once a week during 30 weeks from 10 organic and 10 conventional dairy farms where aflatoxin M1 level was previous tested during 11 months on bulk-tank milk from tanker at the processing plant. Somatic Cells and Total Microbial Counts did not show differences that can be related to the organic production system, suggesting an effect induced by farm size and technical factors. Higher level of Aflatoxin M1 was found in organic than conventional milk.

  5. Recent Development of QCD Factorization for B-> M1 M2

    CERN Document Server

    Yang, Deshan

    2010-01-01

    After briefly introducing the framework of QCD factorization for B-> M1 M2 in the language of the Soft-Collinear Effective Theory, we firstly address the recent efforts on higher-order radiative corrections in QCD factorization. Then we discuss some phenomenologies in B-> V V within the framework of QCD factorization.

  6. 26 CFR 31.3306(m)-1 - American vessel and aircraft.

    Science.gov (United States)

    2010-04-01

    ... 26 Internal Revenue 15 2010-04-01 2010-04-01 false American vessel and aircraft. 31.3306(m)-1... vessel and aircraft. (a) The term “American vessel” means any vessel which is documented (that is....) (b) The term “American aircraft” means any aircraft registered under the laws of the United States...

  7. M1 corticospinal mirror neurons and their role in movement suppression during action observation.

    Science.gov (United States)

    Vigneswaran, Ganesh; Philipp, Roland; Lemon, Roger N; Kraskov, Alexander

    2013-02-04

    Evidence is accumulating that neurons in primary motor cortex (M1) respond during action observation, a property first shown for mirror neurons in monkey premotor cortex. We now show for the first time that the discharge of a major class of M1 output neuron, the pyramidal tract neuron (PTN), is modulated during observation of precision grip by a human experimenter. We recorded 132 PTNs in the hand area of two adult macaques, of which 65 (49%) showed mirror-like activity. Many (38 of 65) increased their discharge during observation (facilitation-type mirror neuron), but a substantial number (27 of 65) exhibited reduced discharge or stopped firing (suppression-type). Simultaneous recordings from arm, hand, and digit muscles confirmed the complete absence of detectable muscle activity during observation. We compared the discharge of the same population of neurons during active grasp by the monkeys. We found that facilitation neurons were only half as active for action observation as for action execution, and that suppression neurons reversed their activity pattern and were actually facilitated during execution. Thus, although many M1 output neurons are active during action observation, M1 direct input to spinal circuitry is either reduced or abolished and may not be sufficient to produce overt muscle activity. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. A fluorescence anisotropy assay for the muscarinic M1 G-protein-coupled receptor.

    Science.gov (United States)

    Huwiler, Kristin G; De Rosier, Therese; Hanson, Bonnie; Vogel, Kurt W

    2010-06-01

    In the search for new chemical entities that interact with G-proteincoupled receptors (GPCRs), assays that quantify efficacy and affinity are employed. Traditional methods for measuring affinity involve radiolabeled ligands. To address the need for homogeneous biochemical fluorescent assays to characterize orthosteric ligand affinity and dissociation rates, we have developed a fluorescence anisotropy (FA) assay for the muscarinic M1 receptor that can be conducted in a 384-well plate. We used membranes from a muscarinic M1 cell line optimized for high-throughput functional assays and the previously characterized fluorescent antagonist BODIPY FL pirenzepine. The affinities of reference compounds were determined in the competitive FA assay and compared with those obtained with a competitive filter-based radioligand-binding assay using [(3)H] N-methylscopolamine. The IC(50) values produced from the FA assay were well-correlated with the radioligand-binding K(i) values (R(2) = 0.98). The dissociation of the BODIPY FL pirenzepine was readily monitored in real time using the FA assay and was sensitive to the presence of the allosteric modulator gallamine. This M1 FA assay offers advantages over traditional radioligandbinding assays as it eliminates radioactivity while allowing investigation of orthosteric or allosteric muscarinic M1 ligands in a homogeneous format.

  9. Stereospecific reduction of virginiamycin M1 as the virginiamycin resistance pathway in Streptomyces virginiae.

    Science.gov (United States)

    Lee, C K; Minami, M; Sakuda, S; Nihira, T; Yamada, Y

    1996-03-01

    In a cell extract of Streptomyces virginiae, virginiamycin M1 was inactivated in the presence of NADPH, while virginiamycin S remained intact. The inactivated product of virginiamycin M1 was isolated, and structure analysis revealed that the inactivation involves reduction of a C-16 carbonyl group leading to the formation of 16-dihydrovirginiamycin M1. Acetonide and benzylidene acetal derivatives were synthesized from the two hydroxyl groups on C-14 and C-16, and the C-16 stereochemistry was determined by 13C nuclear magnetic resonance spectroscopy. Two methyl groups of the acetonide derivative gave 13C signals of 20.1 and 30.1 ppm, indicating that the relative stereochemistry of the C-14 and C-16 hydroxy groups is syn. Furthermore, irradiation of the benzylidene methine proton gave clear nuclear Overhauser effect enhancement of the C-14 or C-16 methine protons, indicating that H-14 and H-16 were in an axial configuration. From the (14S) absolute configuration of natural virginiamycin M1 and the syn relative configuration for the C-14 and C-16 hydroxyl groups of the inactivated product, the C-16 absolute configuration of the inactivated product was thus identified as R.

  10. Multiple outflows in the bipolar planetary nebula M1-16: A molecular line study

    NARCIS (Netherlands)

    Sahai, Raghvendra; Wootten, Alwyn; Schwarz, Hugo E.; Wild, W.

    1994-01-01

    Extensive observations of the molecular gas in the young, compact planetary nebula M1-16 have been made, using the Swedish-ESO-Submillimeter Telescope. A map of the CO J = 2-1 emission shows that the molecular envelope contains both a slow and a fast outflow with expansion velocities of 19 km/s and

  11. Molecular mechanisms that regulate the macrophage M1/M2 polarization balance

    Directory of Open Access Journals (Sweden)

    Nan eWang

    2014-11-01

    Full Text Available As an essential component of innate immunity, macrophages have multiple functions in both inhibiting or promoting cell proliferation and tissue repair. Diversity and plasticity are hallmarks of macrophages. Classical M1 and alternative M2 activation of macrophages, mirroring the Th1–Th2 polarization of T cells, represent two extremes of a dynamic changing state of macrophage activation. M1-type macrophages release cytokines that inhibit the proliferation of surrounding cells and damage contiguous tissue, and M2-type macrophages release cytokines that promote the proliferation of contiguous cells and tissue repair. M1-M2 polarization of macrophage is a tightly controlled process entailing a set of signaling pathways, transcriptional and posttranscriptional regulatory networks. An imbalance of macrophage M1-M2 polarization is often associated with various diseases or inflammatory conditions. Therefore identification of the molecules associated with the dynamic changes of macrophage polarization and understanding their interactions is crucial for elucidating the molecular basis of disease progression and designing novel macrophage-mediated therapeutic strategies.

  12. 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

  13. Aflatoxin M1 in raw milk and binding of aflatoxin by lactic acid bacteria

    Directory of Open Access Journals (Sweden)

    Aflatoxin M1 in raw milk and binding of aflatoxin by lactic acid bacteria

    2010-12-01

    Full Text Available Aflatoxin M1 (AFM1 is potential human carcinogen. Its presence in milk and dairy products represents risk for human health. Therefore, this study was carried out in order to determine thedegree of microbiological contamination by mold, and the potential presence of aflatoxin M1 in 60 raw milk samples, randomly taken from individual producers from different regions of the continental Croatia. The most common genera isolated fungi were Geotrichum (78.3 %, Aspergillus (32.4 % and Penicillium (27.0 %. From total of 60 studied milk samples, 86.66 % were positive for the presence of aflatoxin M1, and 6.66 % of samples were above the prescribed limits. Lactic acid bacteria used in fermented dairy products as a starter culture may play a role in reduction of aflatoxin in foods and nutrients. In this paper the ability of lactic acid bacteria: Lactobacillus rhamnosus GG (ATCC 53103, Lactobacillus delbrueckii S1 and Lactobacillus plantarum A1 to bind aflatoxin M1 was investigated. Standard strain L. rhamnosus GG (ATCC 53103 and L. delbrueckii S1 can significantly (P50 % compared to L. plantarum A1, which binds AFM1 between 18.7 to 28.7 %.

  14. Chlorogenic acid inhibits glioblastoma growth through repolarizating macrophage from M2 to M1 phenotype

    Science.gov (United States)

    Xue, Nina; Zhou, Qin; Ji, Ming; Jin, Jing; Lai, Fangfang; Chen, Ju; Zhang, Mengtian; Jia, Jing; Yang, Huarong; Zhang, Jie; Li, Wenbin; Jiang, Jiandong; Chen, Xiaoguang

    2017-01-01

    Glioblastoma is an aggressive tumor that is associated with distinctive infiltrating microglia/macrophages populations. Previous studies demonstrated that chlorogenic acid (5-caffeoylquinic acid, CHA), a phenolic compound with low molecular weight, has an anti-tumor effect in multiple malignant tumors. In the present study, we focused on the macrophage polarization to investigate the molecular mechanisms behind the anti-glioma response of CHA in vitro and in vivo. We found that CHA treatment increased the expression of M1 markers induced by LPS/IFNγ, including iNOS, MHC II (I-A/I-E subregions) and CD11c, and reduced the expression of M2 markers Arg and CD206 induced by IL-4, resulting in promoting the production of apoptotic-like cancer cells and inhibiting the growth of tumor cells by co-culture experiments. The activations of STAT1 and STAT6, which are two crucial signaling events in M1 and M2-polarization, were significantly promoted and suppressed by CHA in macrophages, respectively. Furthermore, In G422 xenograft mice, CHA increased the proportion of CD11c-positive M1 macrophages and decreased the distribution of CD206-positive M2 macrophages in tumor tissue, consistent with the reduction of tumor weight observed in CHA-treated mice. Overall these findings indicated CHA as a potential therapeutic approach to reduce glioma growth through promoting M1-polarized macrophage and inhibiting M2 phenotypic macrophage. PMID:28045028

  15. Tim-3 promotes intestinal homeostasis in DSS colitis by inhibiting M1 polarization of macrophages.

    Science.gov (United States)

    Jiang, Xingwei; Yu, Jiahui; Shi, Qingzhu; Xiao, Yan; Wang, Wei; Chen, Guojiang; Zhao, Zhi; Wang, Renxi; Xiao, He; Hou, Chunmei; Feng, Jiannan; Ma, Yuanfang; Shen, Beifen; Wang, Lili; Li, Yan; Han, Gencheng

    2015-10-01

    Tim-3 is involved in the physiopathology of inflammatory bowel disease (IBD), but the underlying mechanism is unknown. Here, we demonstrated that, in mouse with DSS colitis, Tim-3 inhibited the polarization of pathogenic pro-inflammatory M1 macrophages, while Tim-3 downregulation or blockade resulted in an increased M1 response. Adoptive transfer of Tim-3-silenced macrophages worsened DSS colitis and enhanced inflammation, while Tim-3 overexpression attenuated DSS colitis by decreasing the M1 macrophage response. Co-culture of Tim-3-overexpressing macrophages with intestinal lymphocytes decreased the pro-inflammatory response. Tim-3 shaped intestinal macrophage polarization may be TLR-4 dependent since Tim-3 blockade failed to exacerbate colitis or increase M1 macrophage response in the TLR-4 KO model. Finally, Tim-3 signaling inhibited phosphorylation of IRF3, a TLR-4 downstream transcriptional factor regulating macrophage polarization. A better understanding of this pathway may shed new light on colitis pathogenesis and result in a new therapeutic strategy.

  16. Experimental Conditions: SE18_S1_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available liver and brain by Orbitrap MS and automated search engine Lipid Search SE18_S1 Mouse liver SE18_S1_M1 34.1...phy. SE18_MS1 Preparation of lipid extract and ESI negative detection by LC-MS analysis SE18_DS1 Identification of phospholipids with Lipid Search default ...

  17. Experimental Conditions: SE18_S2_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available liver and brain by Orbitrap MS and automated search engine Lipid Search SE18_S2 Mouse brain SE18_S2_M1 10.8...phy. SE18_MS1 Preparation of lipid extract and ESI negative detection by LC-MS analysis SE18_DS1 Identification of phospholipids with Lipid Search default ...

  18. 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.; Voert, M.J.A. te

    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

  19. Experimental Conditions: SE37_S16_M1_D1 [Metabolonote[Archive

    Lifescience Database Archive (English)

    Full Text Available opes SE37_S16 Blank (80% methanol) SE37_S16_M1 0mg [MassBase ID] MDLC1_43484 SE37_MS1 Metabolites extraction... with 80% methanol and analysis by LC-Orbitrap-MS SE37_DS1 Peak extraction for unlabeled data 6|ITMS 2 ...

  20. Multiple outflows in the bipolar planetary nebula M1-16: A molecular line study

    NARCIS (Netherlands)

    Sahai, Raghvendra; Wootten, Alwyn; Schwarz, Hugo E.; Wild, W.

    1994-01-01

    Extensive observations of the molecular gas in the young, compact planetary nebula M1-16 have been made, using the Swedish-ESO-Submillimeter Telescope. A map of the CO J = 2-1 emission shows that the molecular envelope contains both a slow and a fast outflow with expansion velocities of 19 km/s and

  1. Aflatoxin M1 in white cheese and butter consumed in Istanbul, Turkey.

    Science.gov (United States)

    Aycicek, Hasan; Yarsan, Ender; Sarimehmetoglu, Belgin; Cakmak, Omer

    2002-10-01

    We studied the occurrence of Aflatoxin M1 (AFM1) in 183 sample of white cheese and butter in Istanbul, Turkey in 2001. The incidence of AFM1 in white cheese and butter samples was as high as 65 and 81, respectively. The particularly high AFM,concentrations imply that more importance should be given to routine analysis of these dairy products.

  2. Effects on Variations in M1 Generation of Durum Wheat (T. durum Thell by Induced Mutagen

    Directory of Open Access Journals (Sweden)

    O. Bilgin

    2005-01-01

    Full Text Available In this research conducted ın Department of Field Crops, Tekirdağ Agricultural Faculty, TrakyaUniversity, the effect of six different gamma ray doses on plant growth in M1 generations derived from twodurum wheat cultivars was investigated.In the experiment, 10 plants in each pot (17 x 40 cm containing 5 kgsoil were grown with three replicates. Total 30 plants for each treatment were used. In M1 generation, numberof leaves, number of roots, seedling height, seedling weight, leaf weight and germination rate were determined.Application of 100-200 gray gamma ray doses did not have any inhibitory effect on investigated characters inseedling growth of M1 generation. On the other hand, 400-500 gray doses significantly inhibited the plantgrowth. 100-200 gray doses did not affect the seed germination rate whereas germination rate decreased with400-500 gray gamma ray applications. At 600 gray dose, only one seed remained viably, rest of them could notsurvive. It was generally observed the highest variations at 300-400 gray gamma doses in M1 plants.

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

    Science.gov (United States)

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

    2016-05-01

    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. Copyright © 2016 Elsevier Inc. All rights reserved.

  4. Increased SMA-M1 coherence in Parkinson's disease - Pathophysiology or compensation?

    Science.gov (United States)

    Pollok, Bettina; Kamp, Daniel; Butz, Markus; Wojtecki, Lars; Timmermann, Lars; Südmeyer, Martin; Krause, Vanessa; Schnitzler, Alfons

    2013-09-01

    Parkinson's disease (PD) is a common neurodegenerative disorder owing to loss of dopaminergic cells. Akinesia - one of the core symptoms of PD - is associated with exaggerated oscillations at beta frequency (13-30 Hz) within the subthalamic nucleus (STN). Thus, enhanced oscillations below 30 Hz are assumed to represent a pathophysiological marker of PD. However, recent data suggest that OFF medication exaggerated beta oscillations within basal ganglia (BG) cortical networks may serve for the compensation of BG dysfunctions. The STN is functionally connected to mesial prefrontal areas like the supplementary motor area (SMA). But, it is still not fully understood how enhanced beta oscillations within the BG exert dominance over the primary motor cortex (M1) thereby yielding motor impairment. The present study, therefore, investigates the effect of dopaminergic state on SMA-M1 functional connectivity using Magnetoencephalography (MEG). MEG data were recorded in 7 patients suffering from PD with preponderance of akinesia during isometric contraction of the right forearm and during rest. Coherence as a measure of functional connectivity between M1 and SMA was calculated OFF and ON medication and correlated with the motor part of the Unified Parkinson's Disease Rating Scale (UPDRS III) and with disease duration. During rest a significant positive correlation between disease duration and SMA-M1 coherence was found ON but not OFF medication. Conversely, during isometric contraction SMA-M1 coherence and UPDRS III were inversely correlated OFF but not ON medication explaining more than 80% of variance. The results favor the hypothesis that OFF medication exaggerated cortical coherence at beta frequency represents a compensatory mechanism rather than a pathophysiological marker per se. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Balancing the excitability of M1 circuitry during movement observation without overt replication

    Directory of Open Access Journals (Sweden)

    Pablo eArias

    2014-09-01

    Full Text Available Although observation of a movement increases the excitability of the motor system of the observer, it does not induce a motor replica. What is the mechanism for replica suppression? We performed a series of experiments, involving a total of 66 healthy humans, to explore the excitability of different M1 circuits and the spinal cord during observation of simple movements. Several strategies were used. In the first and second experimental blocks, we used several delay times from movement onset to evaluate the time-course modulation of the cortico-spinal excitability (CSE, and its potential dependency on the duration of the movement observed; in order to do this single pulse transcranial magnetic stimulation (TMS over M1 was used. In subsequent experiments, at selected delay times from movement-onset, we probed the excitability of the cortico-spinal circuits using three different approaches: i electric cervicomedullary stimulation, to test spinal excitability, ii paired-pulse TMS over M1, to evaluate the cortical inhibitory-excitatory balance (short intracortical inhibition SICI and intracortical facilitation ICF and iii continuous theta-burst stimulation (cTBS, to modulate the excitability of M1cortical circuits. We observed a stereotyped response in the modulation of CSE. At 500ms after movement-onset the ICF was increased; although the most clear-cut effect was a decrease of CSE. The compensatory mechanism was not explained by changes in SICI, but by M1-intracortical circuits targeted by cTBS. Meanwhile, the spinal cord maintained the elevated level of excitability induced when expecting to observe movements, potentially useful to facilitate any required response to the movement observed.

  6. A reliability diagnosis method for electric power optical fiber transmission network based on PMC model%基于PMC模型的电力光纤传输网可靠性诊断方法

    Institute of Scientific and Technical Information of China (English)

    李莉; 高丽媛; 赵旷怡; 吴润泽

    2016-01-01

    电力通信系统可靠性是指电力通信系统在实际连续运行过程中,完成电力系统正常通信需求的能力,是现代电力系统可靠性研究的一个重要部分.保证电力通信网的可靠性是电力系统安全体系中的一个十分重要的方面,本文对现代电力通信网的可靠性诊断问题进行了专门的研究.文章采用PMC互测方法对电力通信网的网络节点进行故障诊断,通过对某地区SDH光网络中故障节点具体诊断,证明该方法能够迅速准确地找出故障节点,从而保证了电力系统的连续运行.%The reliability of electric power communication system refers to the ability of power system to complete the communication needs in the process of actual operation . The reliability of the electric power communication network problem is one of the important aspects of modern power system security system which is specifically studied in this paper . The paper diagnoses the fault nodes in the electric power communication network based on PMC model. The specific diagnosis of a SDH optical network failed nodes proving that the method can identify the failed nodes quickly and accurately, thus ensuring the continuous operation of the power system .

  7. Immunohistochemical localisation of cholinergic muscarinic receptor subtype 1 (M1r) in the guinea pig and human enteric nervous system.

    Science.gov (United States)

    Harrington, A M; Hutson, J M; Southwell, B R

    2007-07-01

    Little is known regarding the location of cholinergic muscarinic receptor 1 (M1r) in the ENS, even though physiological data suggest that M1rs are central to cholinergic neurotransmission. This study localised M1rs in the ENS of the guinea pig ileum and human colon using fluorescence immunohistochemistry and RT-PCR in human colon. Double labelling using antibodies against neurochemical markers was used to identify neuron subytpes bearing M1r. M1r immunoreactivity (IR) was present on neurons in the myenteric and submucosal ganglia. The two antibodies gave similar M1r-IR patterns and M1r-IR was abolished upon antibody preabsorption. M1r-IR was present on cholinergic and nNOS-IR nerve cell bodies in both guinea pig and human myenteric neurons. Presynaptic M1r-IR was present on NOS-IR and VAChT-IR nerve fibres in the circular muscle in the human colon. In the submucosal ganglia, M1r-IR was present on a population of neurons that contained cChAT-IR, but did not contain NPY-IR or calretinin-IR. M1r-IR was present on endothelial cells of blood vessels in the submucosal plexus. The localisation of M1r-IR in the guinea pig and human ENS shown in this study agrees with physiological studies. M1r-IR in cholinergic and nitrergic neurons and nerve fibres indicate that M1rs have a role in both cholinergic and nitrergic transmission. M1r-IR present in submucosal neurons suggests a role in mediating acetylcholine's effect on submucosal sensory and secretomotor/vasodilator neurons. M1r-IR present on blood vessel endothelial cells suggests that M1rs may also mediate acetylcholine's direct effect on vasoactivation.

  8. The Reaction Dynamics of the Reactions Ba+CmH2m+1Br(m=1,2,3,4,5)

    Institute of Scientific and Technical Information of China (English)

    韩克利; 郑锡光; 张瑞勤; 孙本繁; 何国钟; 楼南泉

    1994-01-01

    The internal energy distributions of the nascent BaBr products formed in the reactions ofBa+BrR(R=CH3,C2H5,C3H7,C4H9,C5H11) under the single collision condition have been first studied bylaser-induced fluorescence method.With computer simulations of the experimental spectra,we obtained thevibrational distributions of the BaBr products,and found that the vibrational excitation and reaction cross-section increase with the number of the carbon atoms in the alkyl radical R.The quasitriatomic LEPS poten-tial of the Ba+CH3 reaction has been deduced reversely from the experimental results.The dynamics of thereactions Ba+BrR have been studied by the classical trajectory calculations based on the model LEPS poten-tials.It is concluded that the mass factor and the C-Br bond strength are the major factors affecting the rela-tionship between vibrational excitation and reaction cross-section with the number of the carbon atoms in thealkyl radical R.Furthermore,we obtained all the LEPS potentials of the reactive systems Ba+CmH2m+1 andconfirmed its reliability with ab initio calculations.

  9. 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

  10. FRET-Based Detection of M1 Muscarinic Acetylcholine Receptor Activation by Orthosteric and Allosteric Agonists

    Science.gov (United States)

    Markovic, Danijela; Holdich, Jonathan; Al-Sabah, Suleiman; Mistry, Rajendra; Krasel, Cornelius; Mahaut-Smith, Martyn P.; Challiss, R. A. John

    2012-01-01

    Background and Objective Muscarinic acetylcholine receptors (mAChRs) are 7-transmembrane, G protein-coupled receptors that regulate a variety of physiological processes and represent potentially important targets for therapeutic intervention. mAChRs can be stimulated by full and partial orthosteric and allosteric agonists, however the relative abilities of such ligands to induce conformational changes in the receptor remain unclear. To gain further insight into the actions of mAChR agonists, we have developed a fluorescently tagged M1 mAChR that reports ligand-induced conformational changes in real-time by changes in Förster resonance energy transfer (FRET). Methods Variants of CFP and YFP were inserted into the third intracellular loop and at the end of the C-terminus of the mouse M1 mAChR, respectively. The optimized FRET receptor construct (M1-cam5) was expressed stably in HEK293 cells. Results The variant CFP/YFP-receptor chimera expressed predominantly at the plasma membrane of HEK293 cells and displayed ligand-binding affinities comparable with those of the wild-type receptor. It also retained an ability to interact with Gαq/11 proteins and to stimulate phosphoinositide turnover, ERK1/2 phosphorylation and undergo agonist-dependent internalization. Addition of the full agonist methacholine caused a reversible decrease in M1 FRET (FEYFP/FECFP) that was prevented by atropine pre-addition and showed concentration-dependent amplitude and kinetics. Partial orthosteric agonists, arecoline and pilocarpine, as well as allosteric agonists, AC-42 and 77-LH-28-1, also caused atropine-sensitive decreases in the FRET signal, which were smaller in amplitude and significantly slower in onset compared to those evoked by methacholine. Conclusion The M1 FRET-based receptor chimera reports that allosteric and orthosteric agonists induce similar conformational changes in the third intracellular loop and/or C-terminus, and should prove to be a valuable molecular reagent for

  11. FRET-based detection of M1 muscarinic acetylcholine receptor activation by orthosteric and allosteric agonists.

    Directory of Open Access Journals (Sweden)

    Danijela Markovic

    Full Text Available BACKGROUND AND OBJECTIVE: Muscarinic acetylcholine receptors (mAChRs are 7-transmembrane, G protein-coupled receptors that regulate a variety of physiological processes and represent potentially important targets for therapeutic intervention. mAChRs can be stimulated by full and partial orthosteric and allosteric agonists, however the relative abilities of such ligands to induce conformational changes in the receptor remain unclear. To gain further insight into the actions of mAChR agonists, we have developed a fluorescently tagged M(1 mAChR that reports ligand-induced conformational changes in real-time by changes in Förster resonance energy transfer (FRET. METHODS: Variants of CFP and YFP were inserted into the third intracellular loop and at the end of the C-terminus of the mouse M(1 mAChR, respectively. The optimized FRET receptor construct (M(1-cam5 was expressed stably in HEK293 cells. RESULTS: The variant CFP/YFP-receptor chimera expressed predominantly at the plasma membrane of HEK293 cells and displayed ligand-binding affinities comparable with those of the wild-type receptor. It also retained an ability to interact with Gα(q/11 proteins and to stimulate phosphoinositide turnover, ERK1/2 phosphorylation and undergo agonist-dependent internalization. Addition of the full agonist methacholine caused a reversible decrease in M(1 FRET (F(EYFP/F(ECFP that was prevented by atropine pre-addition and showed concentration-dependent amplitude and kinetics. Partial orthosteric agonists, arecoline and pilocarpine, as well as allosteric agonists, AC-42 and 77-LH-28-1, also caused atropine-sensitive decreases in the FRET signal, which were smaller in amplitude and significantly slower in onset compared to those evoked by methacholine. CONCLUSION: The M(1 FRET-based receptor chimera reports that allosteric and orthosteric agonists induce similar conformational changes in the third intracellular loop and/or C-terminus, and should prove to be a

  12. New probe of M1 and E1 strengths in GDR regions

    Energy Technology Data Exchange (ETDEWEB)

    Hayakawa, T. [Japan Atomic Energy Agency and National Astronomical Observatory in Japan (Japan); Ogata, K. [RCNP, Osaka University (Japan); Miyamoto, S.; Mochizuki, T.; Horikawa, K.; Amano, S. [University of Hyogo (Japan); Imazaki, K.; Li, D.; Izawa, Y. [Institute for Laser Technology (Japan); Chiba, S. [Tokyo Institute of Technology (Japan)

    2014-05-02

    The M1 strengths (or level density of 1{sup +} states) are of importance for estimation of interaction strengths between neutrinos and nuclei for the study of the supernova neutrino-process. In 1957, Agodi predicted theoretically angular distribution of neutrons emitted from states excited via dipole transitions with linearly polarized gamma-ray beam at the polar angle of θ=90° should be followed by a simple function, a + b cos(2φ), where φ, is azimuthal angel. However, this theoretical prediction has not been verified over the wide mass region except for light nuclei as deuteron. We have measured neutron angular distributions with (polarized gamma, n) reactions on Au, Nal, and Cu. We have verified the Agodi's prediction for the first time over the wide mass region. This suggests that (polarized gamma, n) reactions may be useful tools to study M1 strengths in giant resonance regions.

  13. 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.

  14. 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.

  15. Extended M1 sum rule for excited symmetric and mixed-symmetry states in nuclei

    CERN Document Server

    Smirnova, N A; Leviatan, A; Ginocchio, J N; Fransen, C

    2002-01-01

    A generalized M1 sum rule for orbital magnetic dipole strength from excited symmetric states to mixed-symmetry states is considered within the proton-neutron interacting boson model of even-even nuclei. Analytic expressions for the dominant terms in the B(M1) transition rates from the first and second $2^+$ states are derived in the U(5) and SO(6) dynamic symmetry limits of the model, and the applicability of a sum rule approach is examined at and in-between these limits. Lastly, the sum rule is applied to the new data on mixed-symmetry states of 94Mo and a quadrupole d-boson ratio $nd(0^+_1)/nd(2^+_2) \\approx 0.6$ is obtained in a largely parameter-independent way

  16. M=1 and 2 gravitational instabilities in gaseous disks; 1, diffuse gas

    CERN Document Server

    Junqueira, S

    1996-01-01

    We report the results of self-gravitating simulations of spiral galaxies, modeled by stellar and gaseous components, developed to investigate in particular the role of dissipation in the evolution of galaxy disks. The gas disk is simulated by the Beam-Scheme method, where it is considered as a self-gravitating fluid. The results suggest that the gravitational coupling between the stars and gas plays a fundamental role in the formation and dissolution of stellar bars, depending on the gaseous mass concentration and on the degree of dissipation. In addition we remark that initially concentrated gas disks can be unstable to the one-armed (m=1) spiral perturbations, which may explain the lopsided features observed in the gas distribution of the late-type isolated galaxies. The development of the m=1 feature slows down the radial gas flows towards the center, since the large-scale gravity torques are then much weaker.

  17. Cholinergic impact on neuroplasticity drives muscarinic M1 receptor mediated differentiation into neurons.

    Science.gov (United States)

    Benninghoff, Jens; Rauh, Werner; Brantl, Victor; Schloesser, Robert J; Moessner, Rainald; Möller, Hans-Jürgen; Rujescu, Dan

    2013-04-01

    Increasing evidence indicates that canonical neurotransmitters act as regulatory signals during neuroplasticity. Here, we report that muscarinic cholinergic neurotransmission stimulates differentiation of adult neural stem cells in vitro. Adult neural stem cells (ANSC) dissociated from the adult mouse hippocampus were expanded in culture with basic fibroblast growth factor (BFGF) and epidermal growth factor (EGF). Carbachol (CCh), an analog of acetylcholine (ACh) significantly enhanced de novo differentiation into neurons on bFGF- and EGF-deprived stem cells as shown by the percentage of TUJ1 positive cells. By contrast, pirenzepine (PIR), a muscarinic M1 receptor antagonist, reduced the generation of neurons. Activation of cholinergic signaling drives the de novo differentiation of uncommitted stem cells into neurons. These effects appear to be predominantly mediated via the muscarinic M1 receptor subtype.

  18. Commercial scale demonstration enhanced oil recovery by miceller-polymer flooding. M-1 project: facilities report

    Energy Technology Data Exchange (ETDEWEB)

    Knight, B.L. (ed.)

    1977-04-01

    ERDA and Marathon Oil Company contracted together for a commercial scale demonstration of enhanced oil recovery by the Maraflood (TM) oil recovery process. This M-1 Project is located within Sections 15, 16, 21 and 22, T6N, R13W, Crawford County, Illinois, encompassing approximately 407 acres of Robinson Sand reservoir developed in the first decade of the century. The area covers portions of several waterfloods developed on 10-acre spacing in the 1950's that were approaching their economic limit. This report describes all M-1 Project facilities, how they were prepared or constructed, their purpose and how they operate: (1) wells (drilling and completion); (2) production facility; (3) injection facility; and (4) various service systems required during project development and/or operation. (48 fig, 7 tables) (DLC).

  19. 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.

  20. THE BULK INPUT M[X]/M/1 QUEUE WITH WORKING VACATIONS

    Institute of Scientific and Technical Information of China (English)

    Xiuli XU; Mingxin LIU; Xiaohua ZHAO

    2009-01-01

    In this paper, we analyze a bulk input M[X]/M/1 queue with multiple working vacations. A quasi upper triangle transition probability matrix of two-dimensional Markov chain in this model is obtained, and with the matrix analysis method, highly complicated probability generating function(PGF) of the stationary queue length is firstly derived, from which we got the stochastic decomposition result for the stationary queue length which indicates the evident relationship with that of the classical M[X]/M/1 queue without vacation. It is important that we find the upper and the lower bounds of the stationary waiting time in the Laplace transform order using the properties of the conditional Erlang distribution. Furthermore, we gain the mean queue length and the upper and the lower bounds of the mean waiting time.

  1. Formation of Polyhydroxyalkanoate Blends by Pseudomonas pseudoalcaligenes M1-2 from Various Carbon Sources

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Pseudomonas pseudoalcaligenes strain M1-2 isolated from oil-contaminated soil collected from an oilfield in northern China was found to be able to synthesize a blend of polyhydroxyalkanoates (PHAs) containing monomers of 3-hydroxybutyrate (C4), 3-hydroxyvalerate (C5), 3-hydroxyheptanoate (C7), 3-hydroxyoctanoate (C8), 3-hydroxynonanoate (C9), 3-hydroxydecanoate (C10) and 3-hydroxydodecanoate (C12) from various carbon sources.The hydroxyalkanoate (HA) monomer composition varied both quantitatively and qualitatively, depending on the carbon sources used.The presence of octanoate in substrates of myristic acid or tridecanoate promoted the synthesis of HB monomer in the blend.Concentration of octanoate was also found to significantly affect the PHB content in the blend.A PHA biosynthesis pathway in Pseudomonas pseudoalcaligens M1-2 was proposed.

  2. Modulating activity of M1 receptor to the reaction of ileal smooth muscle.

    Science.gov (United States)

    Glaza, Izabela; Szadujkis-Szadurski, Leszek; Szadujkis-Szadurski, Rafał; Gajdus, Marta; Olkowska, Joanna

    2011-08-03

    The subject of the study was determination of the effect of drugs on ileal smooth muscle contraction induced by activation of M(1) type muscarinic receptors. Drugs that have an effect on muscarinic receptors are divided to agonists, with close ties to the receptor and high internal activity and antagonists, with no internal activity. Conducted experiments tested interactions between a broad-spectrum agonist of muscarinic receptors, carbachol and a selective muscarinic receptor antagonist of M(1) type, pirenzepine. Testing was conducted on tissues isolated from rat's intestine. Male Wistar rats with weight between 220 g and 360 g were anesthetized by intraperitoneal injection of urethane (120 mg/kg). Concentration-effect curves were determined with the use of cumulated concentration method, in accordance with the van Rossum method (1963) in Kenakin modification (2006). The purpose of the study was determination of concentration-effect curves for carbachol. This curve was compared with the curve of receptor occupation depending on concentration of this drug. Based on concentration-effect curves, the average value of EC(50) was calculated for carbachol, amounting to 2.44×10(-6) [M/l]. The results confirmed that atropine is effective in stopping contractions caused by carbachol, meeting the conditions of competitive antagonists. Atropine caused the shift of curves for carbachol to the right. Pirenzepine, selectively blocking muscarinic receptors of M(1) type gave similar results. It was proved that in the preparation of gastric fundus smooth muscle, M(1) type receptors occur not only presynaptically, but also postsynaptically.

  3. Modulating activity of M1 receptor to the reaction of ileal smooth muscle

    Directory of Open Access Journals (Sweden)

    Izabela Glaza

    2011-08-01

    Full Text Available Background:The subject of the study was determination of the effect of drugs on ileal smooth muscle contraction induced by activation of M1 type muscarinic receptors. Drugs that have an effect on muscarinic receptors are divided to agonists, with close ties to the receptor and high internal activity and antagonists, with no internal activity. Conducted experiments tested interactions between a broad-spectrum agonist of muscarinic receptors, carbachol and a selective muscarinic receptor antagonist of M1 type, pirenzepine.Material/Methods:Testing was conducted on tissues isolated from rat’s intestine. Male Wistar rats with weight between 220 g and 360 g were anesthetized by intraperitoneal injection of urethane (120 mg/kg. Concentration-effect curves were determined with the use of cumulated concentration method, in accordance with the van Rossum method (1963 in Kenakin modification (2006.Results:The purpose of the study was determination of concentration-effect curves for carbachol. This curve was compared with the curve of receptor occupation depending on concentration of this drug. Based on concentration-effect curves, the average value of EC50 was calculated for carbachol, amounting to 2.44×10–6 [M/l].Conclusions:The results confirmed that atropine is effective in stopping contractions caused by carbachol, meeting the conditions of competitive antagonists. Atropine caused the shift of curves for carbachol to the right. Pirenzepine, selectively blocking muscarinic receptors of M1 type gave similar results. It was proved that in the preparation of gastric fundus smooth muscle, M1 type receptors occur not only presynaptically, but also postsynaptically.

  4. Role of M1 receptor in regulation of gastric fundus smooth muscle contraction

    Directory of Open Access Journals (Sweden)

    Marta Gajdus

    2011-09-01

    Full Text Available Background:The subject of this study is determination of the influence of drugs on gastric fundus smooth muscle contraction induced by activation of muscarinic receptors M1. Experiments tested interactions between a receptor agonist, carbachol and muscarinic receptor antagonists, atropine and pirenzepine.Material/Methods:Testing was conducted on tissues isolated from rat’s stomach. Male Wistar rats with weight between 220 g and 360 g were anesthetized by intraperitoneal injection of urethane (120 mg/kg. The stomach was dissected, and later the gastric fundus was isolated. Tissue was placed in a dish for insulated organs with 20 ml in capacity, filled with Krebs fluid. Results contained in the study are average values ± SE. In order to determine statistical significance, the principles of receptor theory were used (Kenakin modification.Results:According to tests, carbachol, in concentrations ranging between 10–8 M to 10–4 M, in a dosage-dependent way induces gastric fundus smooth muscle contraction. Presented results indicate that carbachol meets the conditions posed to full agonists. On the other hand, atropine, a non-selective muscarinic receptor antagonist, causes a concentration-dependent shift of concentration-effect curve (for carbachol to the right, maintaining maximum reaction. According to analysis of the curve determined, we can deduce that atropine meets the conditions posed to competitive antagonists. The use of pirenzepine, a competitive receptor agonist M1, causes shift of concentration-effect curve (for carbachol to the right, maintaining maximum reaction.Conclusions:From the testing conducted on the preparation of the gastric fundus we can deduce that atropine causes shift of concentration-effect curves for carbachol to the right. A similar effect is released by pirenzepine, selectively blocking muscarinic receptors of M1 type. The results indicate that in the preparation of the gastric fundus smooth muscle, M1 type

  5. Role of M1 receptor in regulation of gastric fundus smooth muscle contraction.

    Science.gov (United States)

    Gajdus, Marta; Szadujkis-Szadurska, Katarzyna; Szadujkis-Szadurski, Leszek; Glaza, Izabela; Szadujkis-Szadurski, Rafał; Olkowska, Joanna

    2011-09-14

    The subject of this study is determination of the influence of drugs on gastric fundus smooth muscle contraction induced by activation of muscarinic receptors M1. Experiments tested interactions between a receptor agonist, carbachol and muscarinic receptor antagonists, atropine and pirenzepine. Testing was conducted on tissues isolated from rat's stomach. Male Wistar rats with weight between 220 g and 360 g were anesthetized by intraperitoneal injection of urethane (120 mg/kg). The stomach was dissected, and later the gastric fundus was isolated. Tissue was placed in a dish for insulated organs with 20 ml in capacity, filled with Krebs fluid. Results contained in the study are average values ± SE. In order to determine statistical significance, the principles of receptor theory were used (Kenakin modification). According to tests, carbachol, in concentrations ranging between 10(-8) M to 10(-4) M, in a dosage-dependent way induces gastric fundus smooth muscle contraction. Presented results indicate that carbachol meets the conditions posed to full agonists. On the other hand, atropine, a non-selective muscarinic receptor antagonist, causes a concentration-dependent shift of concentration-effect curve (for carbachol) to the right, maintaining maximum reaction. According to analysis of the curve determined, we can deduce that atropine meets the conditions posed to competitive antagonists. The use of pirenzepine, a competitive receptor agonist M1, causes shift of concentration-effect curve (for carbachol) to the right, maintaining maximum reaction. From the testing conducted on the preparation of the gastric fundus we can deduce that atropine causes shift of concentration-effect curves for carbachol to the right. A similar effect is released by pirenzepine, selectively blocking muscarinic receptors of M1 type. The results indicate that in the preparation of the gastric fundus smooth muscle, M1 type receptors occur also postsynaptically.

  6. "5M1E"法在生产管理中的运用

    Institute of Scientific and Technical Information of China (English)

    刘秋香

    2010-01-01

    人(man)、机械(machine)、材料(material)、方法(method)、环境(enviroment)、管理(manage)这几个主要环节实行全面质量管理,称为"5M1E"法.在生产管理中应用该法,可以达到提升人品质、提升产品品质,提高员工士气.

  7. Radiationless transitions to atomic M 1,2,3 shells - Results of relativistic theory

    Science.gov (United States)

    Chen, M. H.; Crasemann, B.; Mark, H.

    1983-01-01

    Radiationless transitions filling vacancies in atomic M1, M2, and M3 subshells have been calculated relativistically with Dirac-Hartree-Slater wave functions for ten elements with atomic numbers 67-95. Results are compared with those of nonrelativistic calculations and experiment. Relativistic effects are found to be significant. Limitations of an independent-particle model for the calculation of Coster-Kronig rates are noted.

  8. Study of Mutagenic Effects of M1 Generation of Maize Seeds Irradiated by Heavy Ions

    Institute of Scientific and Technical Information of China (English)

    LUOHong-bing; ZHAOKui; GUOJi-yu; SUILi; NIMei-nan; MEIJun-ping; LUXiu-qin; ZHOUPing; KONGFu-quan; ZHANGGen-fa

    2003-01-01

    In order to study M1 biological effects induced by heavy ion irradiation on maize seeds, the embryos of dry maize seeds are irradiated with 7Li and 12C ions. The experiment is performed at the heavy ion scanning tube of the HI-13 tandem accelerator. The beam goes through a thickness of 25μm. Then the maize seeds are irradiated in the air uniformly.

  9. Cellular stress response in human Müller cells (MIO-M1) after bevacizumab treatment.

    Science.gov (United States)

    Matsuda, Monique; Krempel, Paloma Gava; Marquezini, Mônica Valeria; Sholl-Franco, Alfred; Lameu, Amanda; Monteiro, Mário Luiz R; Miguel, Nádia Campos de Oliveira

    2017-07-01

    Bevacizumab, an anti-vascular endothelial growth factor (VEGF) agent, is widely used in the treatment of retinal vascular diseases. However, due to the essential role Müller cell derived-VEGF plays in the maintenance of retinal neurons and glial cells, cell viability is likely to be affected by VEGF inhibition. We therefore evaluated the effect of bevacizumab-induced VEGF inhibition on Müller cells (MIO-M1) in vitro. MIO-M1 cells were cultured for 12 or 24 h in media containing bevacizumab at 0.25 or 0.5 mg/mL. Controls were cultured in medium only. Cell viability was determined with the trypan blue exclusion test and MTT assay. Caspase-3, beclin-1, glial fibrillary acidic protein (GFAP) and vimentin content were quantified by immunohistochemistry. Gene expression was evaluated by real-time quantitative PCR. Treatment with bevacizumab did not reduce MIO-M1 cell viability, but increased metabolic activity at 24 h (0.5 mg/mL) and induced apoptosis and autophagy, as shown by the increased caspase-3 levels at 12 h (0.25 and 0.5 mg/mL) and the increased beclin levels at 24 h (0.5 mg/mL). Caspase-3 mRNA was upregulated at 12 h and downregulated at 24 h in cells treated with bevacizumab at 0.25 mg/mL. Bevacizumab treatment was also associated with structural protein abnormalities, with decreased GFAP and vimentin content and upregulated GFAP and vimentin mRNA expression. Although bevacizumab did not significantly affect MIO-M1 cell viability, it led to metabolic and molecular changes (apoptosis, autophagy and structural abnormalities) suggestive of significant cellular toxicity. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Fingerprinting the substrate specificity of M1 and M17 aminopeptidases of human malaria, Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Marcin Poreba

    Full Text Available BACKGROUND: Plasmodium falciparum, the causative agent of human malaria, expresses two aminopeptidases, PfM1AAP and PfM17LAP, critical to generating a free amino acid pool used by the intraerythrocytic stage of the parasite for proteins synthesis, growth and development. These exopeptidases are potential targets for the development of a new class of anti-malaria drugs. METHODOLOGY/PRINCIPAL FINDINGS: To define the substrate specificity of recombinant forms of these two malaria aminopeptidases we used a new library consisting of 61 fluorogenic substrates derived both from natural and unnatural amino acids. We obtained a detailed substrate fingerprint for recombinant forms of the enzymes revealing that PfM1AAP exhibits a very broad substrate tolerance, capable of efficiently hydrolyzing neutral and basic amino acids, while PfM17LAP has narrower substrate specificity and preferentially cleaves bulky, hydrophobic amino acids. The substrate library was also exploited to profile the activity of the native aminopeptidases in soluble cell lysates of P. falciparum malaria. CONCLUSIONS/SIGNIFICANCE: This data showed that PfM1AAP and PfM17LAP are responsible for majority of the aminopeptidase activity in these extracts. These studies provide specific substrate and mechanistic information important for understanding the function of these aminopeptidases and could be exploited in the design of new inhibitors to specifically target these for anti-malaria treatment.

  11. Fingerprinting the Substrate Specificity of M1 and M17 Aminopeptidases of Human Malaria, Plasmodium falciparum

    Science.gov (United States)

    Poreba, Marcin; McGowan, Sheena; Skinner-Adams, Tina S.; Trenholme, Katharine R.; Gardiner, Donald L.; Whisstock, James C.; To, Joyce; Salvesen, Guy S.; Dalton, John P.; Drag, Marcin

    2012-01-01

    Background Plasmodium falciparum, the causative agent of human malaria, expresses two aminopeptidases, PfM1AAP and PfM17LAP, critical to generating a free amino acid pool used by the intraerythrocytic stage of the parasite for proteins synthesis, growth and development. These exopeptidases are potential targets for the development of a new class of anti-malaria drugs. Methodology/Principal Findings To define the substrate specificity of recombinant forms of these two malaria aminopeptidases we used a new library consisting of 61 fluorogenic substrates derived both from natural and unnatural amino acids. We obtained a detailed substrate fingerprint for recombinant forms of the enzymes revealing that PfM1AAP exhibits a very broad substrate tolerance, capable of efficiently hydrolyzing neutral and basic amino acids, while PfM17LAP has narrower substrate specificity and preferentially cleaves bulky, hydrophobic amino acids. The substrate library was also exploited to profile the activity of the native aminopeptidases in soluble cell lysates of P. falciparum malaria. Conclusions/Significance This data showed that PfM1AAP and PfM17LAP are responsible for majority of the aminopeptidase activity in these extracts. These studies provide specific substrate and mechanistic information important for understanding the function of these aminopeptidases and could be exploited in the design of new inhibitors to specifically target these for anti-malaria treatment. PMID:22359643

  12. A novel strain of Bacteroides fragilis enhances phagocytosis and polarises M1 macrophages

    Science.gov (United States)

    Deng, Huimin; Li, Zhengchao; Tan, Yafang; Guo, Zhaobiao; Liu, Yangyang; Wang, Ye; Yuan, Yuan; Yang, Ruifu; Bi, Yujing; Bai, Yang; Zhi, Fachao

    2016-01-01

    Commensal Bacteroides fragilis possesses immune-regulatory characteristics. Consequently, it has been proposed as a potential novel probiotic because of its therapeutic effects on immune imbalance, mental disorders and inflammatory diseases. Macrophages play a central role in the immune response, developing either a classical-M1 or an alternative-M2 phenotype after stimulation with various signals. The interactions between macrophages and B. fragilis, however, remain to be defined. Here, a new isolate of B. fragilis, ZY-312, was shown to possess admirable properties, including tolerance to simulated gastric fluid, intestinal fluid and ox bile, and good safety (MOI = 100, 200) and adherent ability (MOI = 100) to LoVo cells. Isolate ZY-312 cell lysate promoted phagocytosis of fluorescent microspheres and pathogenic bacteria in bone marrow-derived macrophage (BMDM) cells. Gene expression of IL-12, iNOS and IL-1β in BMDM cells was increased after treatment with ZY-312, indicating the induction of M1 macrophages, consistent with enhanced secretion of NO. Cell surface expression of CD80 and CD86 was also increased. This study is the first to demonstrate that B. fragilis enhances the phagocytic functions of macrophages, polarising them to an M1 phenotype. Our findings provide insight into the close relationship between B. fragilis and the innate immune system. PMID:27381366

  13. Tramadol differentially regulates M1 and M2 macrophages from human umbilical cord blood.

    Science.gov (United States)

    Zhang, Jun; Chen, Liang; Sun, Yunyun; Li, Yuanhai

    2017-03-17

    Tramadol is an analgesic drug and relieves pain through activating μ-opioid receptors and inhibiting serotonin and noradrenaline reuptake. Emerging evidence shows that it also stimulates immune cells, including NK cells, splenocytes, and lymphocytes, and elevates IL-2 production. However, it remains unknown whether and how tramadol directly affects macrophages. To answer these questions, we collected human umbilical cord blood, isolated macrophages, and examined their responses to tramadol. Although tramadol did not alter resting macrophages and the antigen-presenting function in lipopolysaccharide-activated macrophages, it regulated M1 and M2 macrophages, which are, respectively, transformed by IFN-γ and IL-4. Interestingly, tramadol inhibits production and secretion of cytokines in M1 macrophages, but facilitates the production of inflammation-responding molecules, synthesized in M2 macrophages. We also found that STAT6 cascade pathway in M2 macrophages was significantly enhanced by tramadol. Therefore, this study reveals that tramadol regulates inflammation by inhibiting M1 macrophages (killing process), but promoting the function of M2 macrophages (healing process).

  14. Muscarinic M1 receptors regulate propofol modulation of GABAergic transmission in rat ventrolateral preoptic neurons.

    Science.gov (United States)

    Zhang, Yu; Yu, Tian; Liu, Yang; Qian, Kun; Yu, Bu-Wei

    2015-04-01

    GABAergic neurons within the ventrolateral preoptic area (VLPO) play an important role in sleep-wakefulness regulation. Propofol, a widely used systemic anesthetic, has lately been reported to excite noradrenaline (NA)-inhibited type of VLPO neurons. Present study tested if acetylcholine system takes part in the propofol modulation of GABAergic spontaneous miniature inhibitory postsynaptic currents (mIPSCs) in mechanically dissociated rat VLPO neurons using a conventional whole-cell patch clamp technique. Propofol reversibly decreased mIPSC frequency without affecting the current amplitude, indicating that propofol acts presynaptically to decrease the probability of spontaneous GABA release. The propofol action on GABAergic mIPSC frequency was completely blocked by atropine, a nonselective muscarinic acetylcholine (mACh) receptor antagonist, and pirenzepine, a selective M1 receptor antagonist. These results suggest that propofol acts on M1 receptors on GABAergic nerve terminals projecting to VLPO neurons to inhibit spontaneous GABA release. The M1 receptor-mediated modulation of GABAergic transmission onto VLPO neurons may contribute to the regulation of loss of consciousness induced by propofol.

  15. Chronic treatment with simvastatin upregulates muscarinic M1/4 receptor binding in the rat brain.

    Science.gov (United States)

    Wang, Q; Zengin, A; Ying, W; Newell, K A; Wang, P; Yeo, W; Wong, P T-H; Yenari, M A; Huang, X-F

    2008-06-26

    Statins are increasingly being used for the treatment of a variety of conditions beyond their original indication for cholesterol lowering. We previously reported that simvastatin affected the dopaminergic system in the rat brain. This study aims to investigate regional changes of muscarinic M1/4 receptors in the rat brain after 4-week administration of simvastatin (1 or 10 mg/kg/day). M1/4 receptor distribution and alterations in the post-mortem rat brain were detected by [(3)H]pirenzepine binding autoradiography. Simvastatin (1 mg/kg/day) increased [(3)H]pirenzepine binding, predominantly in the prefrontal cortex (171%, Ppirenzepine binding were observed in the examined regions following simvastatin (10 mg/kg/day) treatment. Our results also provide strong evidence that chronic simvastatin administration, especially at a low dosage, up-regulates M1/4 receptor binding, which is likely to be independent of its muscarinic agonist-like effect. Alterations in [(3)H]pirenzepine binding in the examined brain areas may represent the specific regions that mediate the clinical effects of simvastatin treatment on cognition and memory via the muscarinic cholinergic system. These findings contribute to a better understanding of the critical roles of simvastatin in treating neurodegenerative disorders, via muscarinic receptors.

  16. The mechanism of the anticancer function of M1 macrophages and their use in the clinic

    Institute of Scientific and Technical Information of China (English)

    Xing-Qing Pan

    2012-01-01

    M1-type macrophages are capable of inducing lysis in various types of cancer cells,but the mechanism of action is unclear.It has been noted that an "unknown protein" produced together with protease by activated macrophages is responsible for this action.Activated M1 macrophages have been recently reported to produce family 18 chitinases,all of which have been named chitotriosidase.Our experiments have demonstrated that family 18 chitinases work together with proteases and can damage various cancer cells both in vitro and in vivo.Thus,in this article,we suggest that the 50-kDa chitotriosidase is the reported "unknown protein".In addition,we discuss how to properly stimulate activated M1 macrophages to produce 50-kDa chitotriosidases and proteases for destroying cancer cells.Because family 19 chitinase has recently been reported to kill cancer cells,we also discuss the possibility of directly using human family 18 chitotriosidase and the humanized plant family 19 chitinase for cancer treatment.

  17. The detection of C60 in the well-characterized planetary nebula M1-11

    CERN Document Server

    Otsuka, Masaaki; Hyung, S; Sargent, B A; Meixner, M; Tajitsu, A; Yanagisawa, K

    2013-01-01

    We performed multiwavelength observations of the young planetary nebula (PN) M1-11 and obtained its elemental abundances, dust mass, and the evolutionary status of the central star. The AKARI/IRC, VLT/VISIR, and Spitzer/IRS spectra show features due to carbon-rich dust, such as the 3.3, 8.6, and 11.3 um features due to polycyclic aromatic hydrocarbons (PAHs), a smooth continuum attributable to amorphous carbon, and the broad 11.5 and 30 um features often ascribed to SiC and MgS, respectively. We also report the presence of an unidentified broad feature at 16-22 um, similar to the feature found in Magellanic Cloud PNe with either C-rich or O-rich gas-phase compositions. We identify for the first time in M1-11 spectral lines at 8.5 (blended with PAH), 17.3, and 18.9 um that we attribute to the C60 fullerene. This identification is strengthened by the fact that other Galactic PNe in which fullerenes are detected, have similar central stars, similar gas-phase abundances, and a similar dust composition to M1-11. T...

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

    Energy Technology Data Exchange (ETDEWEB)

    Guliants, Vadim

    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.

  19. Aflatoxin M1 in raw milk in Qazvin Province, Iran: a seasonal study.

    Science.gov (United States)

    Fallah, Aziz A; Barani, Afshin; Nasiri, Zeinab

    2015-01-01

    Occurrence of aflatoxin M1 (AFM1) was determined in 254 samples of raw milk obtained from dairy cow farms of Qazvin Province, Iran. Aflatoxin M1 analysis was carried out by using the competitive enzyme-linked immunosorbent assay technique for screening and high-performance liquid chromatography with fluorescence detection for confirmatory purposes. The limit of detection and quantification of the confirmatory method were 0.003 and 0.01 µg/l, respectively. Aflatoxin M1 was detected in 204 analysed samples (80.3%), ranging from 0.011 to 0.321 μg/l, and 144 samples (56.7%) had levels above the Iranian national standard limit of 0.050 μg/l. Considering the seasonal variability, the occurrence and levels of AFM1 in samples obtained in winter were significantly higher (P < 0.05) than those obtained in summer. The results of this survey indicate the usefulness of a monitoring programme to supervise food safety for consumers.

  20. 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.

  1. Forkhead transcription factor FoxM1 regulates mitotic entry and prevents spindle defects in cerebellar granule neuron precursors

    NARCIS (Netherlands)

    Schueller, Ulrich; Zhao, Qing; Godinho, Susana A.; Heine, Vivi M.; Medema, Rene H.; Pellman, David; Rowitch, David H.

    2007-01-01

    The forkhead transcription factor FoxM1 has been reported to regulate, variously, proliferation and/or spindle formation during the G(2)/M transition of the cell cycle. Here we define specific functions of FoxM1 during brain development by the investigation of FoxM1 loss-of-function mutations in the

  2. 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

  3. Production of a monoclonal antibody against aflatoxin M1 and its application for detection of aflatoxin M1 in fortified milk

    Directory of Open Access Journals (Sweden)

    Umarphorn Chadseesuwan

    2016-10-01

    Full Text Available Aflatoxin M1 (AFM1 is a toxic metabolite of the fungal product aflatoxin found in milk. For food safety concern, maximum residual limits of AFM1 in milk and dairy products have been differently enforced in many countries. A suitable detection method is required to screen a large number of product samples for the AFM1 contamination. In this study, monoclonal antibodies (MAbs against AFM1 were generated using a conventional somatic cell fusion technique. After screening, five MAbs (AFM1-1, AFM1-3, AFM1-9, AFM1-11, and AFM1-17 were obtained that showed cross-reactivity with aflatoxin B1 (AFB1 and aflatoxin G1 (AFG1 but with no other tested compounds. An indirect competitive enzyme-linked immunosorbent assay (ELISA using a partially purified MAb and antigen-coated plates yielded the best sensitivity with the 50% inhibition concentration (IC50 and the limit of detection (LOD values of 0.13 ng/mL and 0.04 ng/mL, respectively. This indirect competitive ELISA was used to quantify the amount of fortified AFM1 in raw milk. The precision and accuracy in terms of % coefficient of variation (CV and % recovery of the detection was investigated for both intra- (n = 6 and inter- (n = 12 variation assays. The % CV was found in the range of 3.50–15.8% and 1.32–7.98%, respectively, while the % recovery was in the range of 92–104% and 100–103%, respectively. In addition, the indirect ELISA was also used to detect AFM1 fortified in processed milk samples. The % CV and % recovery values were in the ranges of 0.1–33.0% and 91–109%, respectively. Comparison analysis between the indirect ELISA and high performance liquid chromatography was also performed and showed a good correlation with the R2 of 0.992 for the concentration of 0.2–5.0 ng/mL. These results indicated that the developed MAb and ELISA could be used for detection of AFM1 in milk samples.

  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. Effect of pirenzepine, a muscarinic M1 receptor antagonist, on amygdala kindling in rat.

    Science.gov (United States)

    Eşkazan, E; Aker, R; Onat, F; Köseoğlu, S; Gören, M Z; Hasanoğlu, A

    1999-11-01

    Kindling, an animal model of complex partial seizures with secondary generalization, is performed by daily application of low-intensity electrical brain stimulation. The purpose of this study was to investigate the role of muscarinic M1 receptors on amygdala kindling in the rat. Bipolar nichrome stimulation and recording electrodes were stereotaxically implanted into the right and left basolateral amygdala. Extradural recording electrodes were also placed bilaterally in the skull over the cortex. Amygdala stimulation was applied twice daily at the current intensity of afterdischarge threshold. Seizure intensity was graded by using Racine's standard five-stage scale. In the first group of experiments, saline or pirenzepine (10, 25, 50 and 100 nmol), a muscarinic M1 receptor antagonist, was injected intracerebroventricularly 1 h before the electrical stimulation. In the second group of experiments, rats were kindled to full stage 5 seizures. After a recovery period, 50 nmol of pirenzepine was administered intracerebroventricularly to kindled animals. In the first group of experiments, none of the animals pretreated with the doses of 50 and 100 nmol of pirenzepine reached a stage 5 seizure. Pirenzepine significantly retarded kindling seizure development and increased the total number of stimulations required to reach the first stage 5 seizure. Afterdischarge duration was also reduced in the pirenzepine 10 nmol group as compared with that in the saline-pretreated group. In the second group, seizure stage and afterdischarge duration were not affected by pirenzepine in fully-kindled animals. The findings of this study suggest that muscarinic M1 receptors may have a critical role in the development of kindling epileptic activity, but not in already kindled seizures.

  6. Spatio-kinematics of the optical nebula M1-92 with HST/STIS

    Science.gov (United States)

    Ramos-Medina, J.; Sánchez-Contreras, C.; Sahai, R.; Bujarrabal, V.; Castro-Carrizo, A.; Morris, M.

    2014-04-01

    We report optical long-slit spectroscopy with HST/STIS of the well known pre-Planetary Nebula (pPN) M1-92 (a.k.a. Minkowski's footprint). Complementary long-slit echelle spectra obtained with Keck II+ESI have been also used. We have used our high-angular (~0.1arcsec) resolution spectra to characterize the spatio-kinematic structure of the optical nebula of this object. From the analysis of the Halpha two-dimensional profile we identify several distinct nebular components at different spatial scales. The blue-shifted absorption component of the broad 'P cygni'-like profile of the Halpha emission is spatially and spectrally resolved and is found to be composed of not one but two different features centered at Vlsr~-600 and -200 km/s. To assist in the interpretation of the data, we have used a simple spatio-kinematic model which has allowed us to describe the main properties of the fast, bipolar winds (expanding with velocities of up to ~700 km/s) running inside the reflection lobes of M1-92 and that produce the absorptions. At the nebula center, we also discover an equatorially extended H-alpha emitting region that is expanding at moderate velocity (~300 km/s) in the direction perpendicular to the lobes. We have estimated the column density of the inner post-AGB winds and other physical parameters that have helped improving our understanding of the evolutionary history of M1-92.

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

    Energy Technology Data Exchange (ETDEWEB)

    Tokumitsu, Naoki; Sako, Kazuhiro; Aizawa, Shizuka; Shirai, Wakako [Nayoro City Hospital, Hokkaido (Japan)

    2002-07-01

    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)

  8. ISSR Analysis of M_1 Generation of Gladiolus hybridus Hort Treated by EMS

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Gladiolus hybridus Hort is one of famous cutting flowers,being famous of big size,bright color,various shapes and long bloom period.New species should be cultivated in order to meet consumers' needs.Mutagenic breeding is a shortcut to cultivate new species of flowers.In this study,corm bud of G.hybridus Hort was treated with different concentrations of EMS.Then M 1 generation was analyzed by ISSR.Results showed that EMS was a very effective mutagenic agent for the corm bud of G.hybridus Hort.With the increa...

  9. 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

  10. Daniel Hertz SA M1落地式音箱

    Institute of Scientific and Technical Information of China (English)

    许成文

    2011-01-01

    Daniel Hertz SA M1落地式音箱在箱体结构上取经典造型。毫无疑问,Daniel Hertz的SAM1落地式音箱甫一亮相干市场,便已经奠定了它作为一代经典作品的基础——这不仅使其采用最经典的前障板布局和单元配置,在更大的程度上还包括它的综合技术内涵。

  11. THE DETECTION OF C60 IN THE WELL-CHARACTERIZED PLANETARY NEBULA M1-11

    Energy Technology Data Exchange (ETDEWEB)

    Otsuka, Masaaki; Kemper, F. [Institute of Astronomy and Astrophysics, Academia Sinica, P.O. Box 23-141, Taipei 10617, Taiwan (China); Hyung, S. [School of Science Education (Astronomy), Chungbuk National University, CheongJu, Chungbuk 361-763 (Korea, Republic of); Sargent, B. A.; Meixner, M. [Space Telescope Science Institute, 3700 San Martin Drive, Baltimore, MD 21218 (United States); Tajitsu, A. [Subaru Telescope, NAOJ, 650 North A' ohoku Place, Hilo, HI 96720 (United States); Yanagisawa, K., E-mail: otsuka@asiaa.sinica.edu.tw [Okayama Astrophysical Observatory (OAO), NAOJ, Kamogata, Okayama 719-0232 (Japan)

    2013-02-10

    We performed multiwavelength observations of the young planetary nebula (PN) M1-11 and obtained its elemental abundances, dust mass, and the evolutionary status of the central star. The AKARI/IRC, VLT/VISIR, and Spitzer/IRS spectra show features due to carbon-rich dust, such as the 3.3, 8.6, and 11.3 {mu}m features due to polycyclic aromatic hydrocarbons (PAHs), a smooth continuum attributable to amorphous carbon, and the broad 11.5 and 30 {mu}m features often ascribed to SiC and MgS, respectively. We also report the presence of an unidentified broad feature at 16-22 {mu}m, similar to the feature found in Magellanic Cloud PNe with either C-rich or O-rich gas-phase compositions. We identify for the first time in M1-11 spectral lines at 8.5 (blended with PAH), 17.3, and 18.9 {mu}m that we attribute to the C{sub 60} fullerene. This identification is strengthened by the fact that other Galactic PNe in which fullerenes are detected have similar central stars, similar gas-phase abundances, and a similar dust composition to M1-11. The weak radiation field due to the relatively cool central stars in these PNe may provide favorable conditions for fullerenes to survive in the circumstellar medium. Using the photoionization code CLOUDY, combined with a modified blackbody, we have fitted the {approx}0.1-90 {mu}m spectral energy distribution (SED) and determined the dust mass in the nebula to be {approx}3.5 Multiplication-Sign 10{sup -4} M {sub Sun }. Our chemical abundance analysis and SED model suggest that M1-11 is perhaps a C-rich PN with C/O ratio in the gas phase of +0.19 dex, and that it evolved from a 1-1.5 M {sub Sun} star.

  12. Scaled-energy spectroscopy of helium \\|M\\|=1 Rydberg atoms in a static electric field

    Science.gov (United States)

    Kips, Annemieke; Vassen, Wim; Hogervorst, Wim; Dando, Paul A.

    1998-10-01

    We present scaled-energy spectra on helium Rydberg atoms in a static electric field. \\|M\\|=1 states were studied in excitation from the 2 1S0 metastable state. Spectra were recorded for ɛ=-2.940(4), ɛ=-2.350(4), both below the saddle point, and ɛ=-1.760(4), above the saddle point. Closed-orbit theory was applied to interpret the spectra. A recent extension to closed-orbit theory, incorporating core effects, was used. This significantly improved agreement between experiment and theory.

  13. Enhancement of M1 Transition Rates at High Spin in 90Mo

    Institute of Scientific and Technical Information of China (English)

    WU Xiao-Guang; YANG Chun-Xiang; LI Guang-Sheng; PENG Zhao-Hua; WEN Shu-Xian; HAN Guang-Bing; LI Cheng-Po; LU Shao-Jun; WU Shao-Yong; YUAN Guan-Jun

    2001-01-01

    High spin states in 90Mo have been populated through the 59Co (35C1,2p2n) 90Mo reaction at a beam energy of116 Me V. Level lifetimes of the positive-parity decay sequence are measured by using the Doppler shift attenuationmethod. It is observed that the M1 transition strengths show a substantial enhancement at high spin. Thisbehaviour may be related to occupation of high Ω orbitals by a pair of g9/2 protons. A deformed, oblate, shapeis suggested above the 13+ state.

  14. 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.

  15. AN M/M/1/N FEEDBACK QUEUING SYSTEM WITH REVERSE BALKING

    Directory of Open Access Journals (Sweden)

    Rakesh Kumar

    2015-06-01

    Full Text Available In this paper we develop an M/M/1/N feedback queuing system with reverse balking. Reverse balking is a type of customer behavior according to which an arriving customer joins a system with high probability if he encounters large system size and vice-versa. This behavior of a customer can be observed in many businesses such as investment. Feedback customer in queuing literature refers to a customer who is unsatisfied with incomplete, partial or unsatisfactory service. We derive the steady-state solution of the model and obtain some important measures of performance. Sensitivity analysis of the model is also performed with respect to the parameters involved.

  16. E1M1 and E1E2 transition probabilities in one-electron ions

    Science.gov (United States)

    Labzowsky, L. N.; Shonin, A. V.

    2004-12-01

    The quantum electrodynamical (QED) theory of the two-photon transitions in hydrogenlike ions is presented. The emission probability for 2s→2γ(E1)+1s transitions is calculated and compared to the results of the previous calculations. The emission probabilities 2p→γ(E1)+γ(E2)+1s and 2p→γ(E1)+γ(M1)+1s are also calculated for the nuclear charge Z values 1⩽Z⩽100. This is the first calculation of the two latter probabilities. The results are given in two different gauges.

  17. STS-34 crewmembers sit in M1-13 APC during emergency egress training at KSC

    Science.gov (United States)

    1989-01-01

    STS-34 crewmembers sit in M1-13 Armored Personnel Carrier (APC) during emergency egress training at KSC's shuttle landing facility (SLF) prior to terminal countdown demonstration test (TCDT) activities. Wearing launch and entry suits (LESs), are (from left) Mission Specialist (MS) Ellen S. Baker, MS Shannon W. Lucid, Commander Donald E. Williams (right side, in back), MS Franklin R. Chang-Diaz, and Pilot Michael J. McCulley (holding headset). View provided by KSC with alternate number KSC-89PC-871.

  18. 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 joi...... 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....

  19. M1-46: A Case Study on Multiple-Shell Planetary Nebula Formation

    Science.gov (United States)

    Guerrero, M. A.; Manchado, A.; Stanghellini, L.; Herrero, A.

    1996-06-01

    We discuss in detail the evolutionary path of the multiple-shell planetary nebula M1-46, in the light of our new observations. The velocities of the halo and main nebula correspond to a dynamical time lap between the shells of about 6.8 x 104 yr. By means of a non-LTE analysis of the central star's spectrum, we derived a stellar temperature of Teff = 45,000 K, which, coupled to the visual magnitude and an appropriate bolometric correction, gives a stellar luminosity of 5370 Lsun. The mass of the central star has been evaluated to be 0.6 Msun, and its interpulse time on the asymptotic giant branch is 7.6 x 104 yr. The agreement between the observed intershell time lap and the evolutionary interpulse time lap points to the fact that the formation of this planetary nebula could be ascribed to the gasping mass loss associated with the thermal pulses at the thermally pulsating asymptotic giant branch. The high-resolution spatially resolved observations reveal the presence of different kinematical components in the main nebula which cannot be understood in a homogeneous expanding shell scenario. As regards the chemical abundances, M1-46 has the typical abundances of a type II planetary nebula. No definite abundance gradient between the shells is found.

  20. 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

  1. 新加坡M1与Vodafone达成漫游协议

    Institute of Scientific and Technical Information of China (English)

    2006-01-01

    为了让经常旅游的客户能够更方便有效地使用数据业务。新加坡M1用户推出了数据漫游业务。用户在Vodafone的网络上进行数据漫游时,将只需支付本地数据资费,从而节省了60%的数据使用费。这一优惠目前可以在8个有Vodafone网络运营的国家实现,今年早些时候将有超过30个国家可以享受到这项服务,包括一些很流行的漫游目的地,如香港、法国、英国、澳大利亚和德国。随着数据漫游资费的推出,M1成为新加坡第一个提供在Vodafone网络上的单一数据漫游资费的移动运营商。

  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

    2009-02-24

    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.

  3. Determination of aflatoxin M1 levels in Iranian white and cream cheese.

    Science.gov (United States)

    Fallah, Aziz A; Jafari, Tina; Fallah, Ali; Rahnama, Mohammad

    2009-08-01

    A screening survey on the occurrence of aflatoxin M1 (AFM1) was accomplished on 210 cheese samples composed of white cheese (116 samples) and cream cheese (94 samples) purchased from popular markets in central part of Iran (Esfahan and Yazd provinces). The quantitative analysis of AFM1 levels in the samples was performed by using the competitive enzyme-linked immunosorbent assay (ELISA) technique. Aflatoxin M1 at measurable level (50 ng/kg) was detected in 161 (76.6%) samples, consisting of 93 (80.1%) white and 68 (72.3%) cream cheese samples. The concentration of AFM1 in the samples ranged from 52.1 to 785.4 ng/kg. Comparing to legal regulation (250 ng/kg) accepted by some of the countries, 24.2% of the samples exceeded the accepted limit. Among these, the AFM1 levels in 28.4% of white and 19.1% of cream cheese samples were not in accordance with the safety limit. The results indicated that contamination of the samples with AFM1 in such a level appear to be a potential hazard for public health. This paper represents the data of the first survey on the occurrence of AFM1 in cheeses consumed in central part of Iran.

  4. Pirenzepine Promotes the Dimerization of Muscarinic M1 Receptors through a Three-step Binding Process*

    Science.gov (United States)

    Ilien, Brigitte; Glasser, Nicole; Clamme, Jean-Pierre; Didier, Pascal; Piemont, Etienne; Chinnappan, Raja; Daval, Sandrine B.; Galzi, Jean-Luc; Mely, Yves

    2009-01-01

    Ligand binding to G protein-coupled receptors is a complex process that involves sequential receptor conformational changes, ligand translocation, and possibly ligand-induced receptor oligomerization. Binding events at muscarinic acetylcholine receptors are usually interpreted from radioligand binding studies in terms of two-step ligand-induced receptor isomerization. We report here, using a combination of fluorescence approaches, on the molecular mechanisms for Bodipy-pirenzepine binding to enhanced green fluorescent protein (EGFP)-fused muscarinic M1 receptors in living cells. Real time monitoring, under steady-state conditions, of the strong fluorescence energy transfer signal elicited by this interaction permitted a fine kinetic description of the binding process. Time-resolved fluorescence measurements allowed us to identify discrete EGFP lifetime species and to follow their redistribution upon ligand binding. Fluorescence correlation spectroscopy, with EGFP brightness analysis, showed that EGFP-fused muscarinic M1 receptors predominate as monomers in the absence of ligand and dimerize upon pirenzepine binding. Finally, all these experimental data could be quantitatively reconciled into a three-step mechanism, with four identified receptor conformational states. Fast ligand binding to a peripheral receptor site initiates a sequence of conformational changes that allows the ligand to access to inner regions of the protein and drives ligand-receptor complexes toward a high affinity dimeric state. PMID:19451648

  5. Fluorescent pirenzepine derivatives as potential bitopic ligands of the human M1 muscarinic receptor.

    Science.gov (United States)

    Tahtaoui, Chouaib; Parrot, Isabelle; Klotz, Philippe; Guillier, Fabrice; Galzi, Jean-Luc; Hibert, Marcel; Ilien, Brigitte

    2004-08-12

    Following a recent description of fluorescence resonance energy transfer between enhanced green fluorescent protein (EGFP)-fused human muscarinic M1 receptors and Bodipy-labeled pirenzepine, we synthesized seven fluorescent derivatives of this antagonist in order to further characterize ligand-receptor interactions. These compounds carry Bodipy [558/568], Rhodamine Red-X [560/580], or Fluorolink Cy3 [550/570] fluorophores connected to pirenzepine through various linkers. All molecules reversibly bind with high affinity to M1 receptors (radioligand and energy transfer binding experiments) provided that the linker contains more than six atoms. The energy transfer efficiency exhibits modest variations among ligands, indicating that the distance separating EGFP from the fluorophores remains almost constant. This also supports the notion that the fluorophores may bind to the receptor protein. Kinetic analyses reveal that the dissociation of two Bodipy derivatives (10 or 12 atom long linkers) is sensitive to the presence of the allosteric modulator brucine, while that of all other molecules (15-24 atom long linkers) is not. The data favor the idea that these analogues might interact with both the acetylcholine and the brucine binding domains. Copyright 2004 American Chemical Society

  6. Pirenzepine promotes the dimerization of muscarinic M1 receptors through a three-step binding process.

    Science.gov (United States)

    Ilien, Brigitte; Glasser, Nicole; Clamme, Jean-Pierre; Didier, Pascal; Piemont, Etienne; Chinnappan, Raja; Daval, Sandrine B; Galzi, Jean-Luc; Mely, Yves

    2009-07-17

    Ligand binding to G protein-coupled receptors is a complex process that involves sequential receptor conformational changes, ligand translocation, and possibly ligand-induced receptor oligomerization. Binding events at muscarinic acetylcholine receptors are usually interpreted from radioligand binding studies in terms of two-step ligand-induced receptor isomerization. We report here, using a combination of fluorescence approaches, on the molecular mechanisms for Bodipy-pirenzepine binding to enhanced green fluorescent protein (EGFP)-fused muscarinic M1 receptors in living cells. Real time monitoring, under steady-state conditions, of the strong fluorescence energy transfer signal elicited by this interaction permitted a fine kinetic description of the binding process. Time-resolved fluorescence measurements allowed us to identify discrete EGFP lifetime species and to follow their redistribution upon ligand binding. Fluorescence correlation spectroscopy, with EGFP brightness analysis, showed that EGFP-fused muscarinic M1 receptors predominate as monomers in the absence of ligand and dimerize upon pirenzepine binding. Finally, all these experimental data could be quantitatively reconciled into a three-step mechanism, with four identified receptor conformational states. Fast ligand binding to a peripheral receptor site initiates a sequence of conformational changes that allows the ligand to access to inner regions of the protein and drives ligand-receptor complexes toward a high affinity dimeric state.

  7. Molecular Probes for Muscarinic Receptors: Derivatives of the M1-Antagonist Telenzepine

    Science.gov (United States)

    Karton, Yishai; Baumgold, Jesse; Handen, Jeffrey S.; Jacobson, Kenneth A.

    2012-01-01

    Functionalized congeners of the M1-selective muscarinic antagonist telenzepine (4,9-dihydro-3-methyl-4-[(4-methyl-1-piperazinyl)acetyl]-10H-thieno[3,4–b][1,5]benzodiazepin-10-one) were developed and found to bind to the receptor with affinities (Ki values) in approximately the nanomolar range. The derivatives contain a 10-aminodecyl group, which provides a nucleophilic functionality for further derivatization. The attachment of a spacer chain to the distal piperazinyl nitrogen was based on previous findings of enhanced affinity at muscarinic receptors in an analogous series of alkylamino derivatives of pirenzepine [J. Med. Chem. (1991) 34, 2133–2145]. The telenzepine derivatives contain prosthetic groups for radioiodination, protein cross-linking, photoaffinity labeling, and fluorescent labeling and biotin for avidin complexation. The affinity for muscarinic receptors in rat forebrain (mainly m1 subtype) was determined in competitive binding assays vs [3H]-N-methylscopolamine. A (p-aminophenyl)-acetyl derivative for photoaffinity labeling had a Ki value of 0.29 nM at forebrain muscarinic receptors (16-fold higher affinity than telenzepine). A biotin conjugate displayed a Ki value of 0.60 nM at m2-receptors and a 5-fold selectivity versus forebrain. The high affinity of these derivatives makes them suitable for the characterization of muscarinic receptors in pharmacological and spectroscopic studies, for peptide mapping, and for histochemical studies. PMID:1520727

  8. 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

    2017-05-01

    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.

  9. 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.

  10. 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.

  11. The Truth-Telling Motor Cortex: Response Competition in M1 Discloses Deceptive Behaviour

    Directory of Open Access Journals (Sweden)

    Aviad A. Hadar

    2011-05-01

    Full Text Available Recent studies have suggested that circuits associated with response conflict and response inhibition are strongly implicated in deception. Using single-pulse transcranial magnetic stimulation (TMS, we examined whether conflict between competing responses in primary motor cortex (M1 can be used for discriminating between intentionally false and true facial recognition. Participants used little finger and thumb key-presses to lie or tell the truth regarding their familiarity with a series of famous and nonfamous faces. Single-pulse TMS was administered to M1 at three intervals prior to response execution in order to evoke motor evoked potentials (MEPs in both Abductor Digiti Minimi (ADM and first dorsal interosseous (FDI of the right hand. As predicted, we found that the MEP of the nonresponding digit was greater than the MEP of the responding digit when participants prepared to engage in deception, while a mirror-reversed pattern was observed for truth telling. This effect did not interact with the stimulation interval suggesting consistent activation of the motor plan representing the truth throughout the response preparation process. We discuss these results with reference to models of response selection and procedures for the detection of deception.

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

    Science.gov (United States)

    Tabar, Emre; Yakut, Hakan; Kuliev, Ali Akbar

    2017-01-01

    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 229-233Th and 233-239U 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 228-232Th and 232-238U nuclei. For 235U 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.

  13. Carboxyl- and amino-functionalized polystyrene nanoparticles differentially affect the polarization profile of M1 and M2 macrophage subsets.

    Science.gov (United States)

    Fuchs, Ann-Kathrin; Syrovets, Tatiana; Haas, Karina A; Loos, Cornelia; Musyanovych, Anna; Mailänder, Volker; Landfester, Katharina; Simmet, Thomas

    2016-04-01

    Macrophages are key regulators of innate and adaptive immune responses. Exposure to microenvironmental stimuli determines their polarization into proinflammatory M1 and anti-inflammatory M2 macrophages. M1 exhibit high expression of proinflammatory TNF-α and IL-1β, and M2 promote tissue repair, but likewise support tumor growth and cause immune suppression by expressing IL-10. Thus, the M1/M2 balance critically determines tissue homeostasis. By using carboxyl- (PS-COOH) and amino-functionalized (PS-NH2) polystyrene nanoparticles, the effects of surface decoration on the polarization of human macrophages were investigated. The nanoparticles did not compromise macrophage viability nor did they affect the expression of the M1 markers CD86, NOS2, TNF-α, and IL-1β. By contrast, in M2, both nanoparticles impaired expression of scavenger receptor CD163 and CD200R, and the release of IL-10. PS-NH2 also inhibited phagocytosis of Escherichia coli by both, M1 and M2. PS-COOH did not impair phagocytosis by M2, but increased protein mass in M1 and M2, TGF-β1 release by M1, and ATP levels in M2. Thus, nanoparticles skew the M2 macrophage polarization without affecting M1 markers. Given the critical role of the M1 and M2 polarization for the immunological balance in patients with cancer or chronic inflammation, functionalized nanoparticles might serve as tools for reprogramming the M1/M2 polarization.

  14. Involvement of an Arginine Triplet in M1 Matrix Protein Interaction with Membranes and in M1 Recruitment into Virus-Like Particles of the Influenza A(H1N1)pdm09 Virus

    Science.gov (United States)

    Moncorgé, Olivier; Panthu, Baptiste; Prchal, Jan; Décimo, Didier; Ohlmann, Théophile; Lina, Bruno; Favard, Cyril; Decroly, Etienne; Ottmann, Michèle; Roingeard, Philippe; Muriaux, Delphine

    2016-01-01

    The influenza A(H1N1)pdm09 virus caused the first influenza pandemic of the 21st century. In this study, we wanted to decipher the role of conserved basic residues of the viral M1 matrix protein in virus assembly and release. M1 plays many roles in the influenza virus replication cycle. Specifically, it participates in viral particle assembly, can associate with the viral ribonucleoprotein complexes and can bind to the cell plasma membrane and/or the cytoplasmic tail of viral transmembrane proteins. M1 contains an N-terminal domain of 164 amino acids with two basic domains: the nuclear localization signal on helix 6 and an arginine triplet (R76/77/78) on helix 5. To investigate the role of these two M1 basic domains in influenza A(H1N1)pdm09 virus molecular assembly, we analyzed M1 attachment to membranes, virus-like particle (VLP) production and virus infectivity. In vitro, M1 binding to large unilamellar vesicles (LUVs), which contain negatively charged lipids, decreased significantly when the M1 R76/77/78 motif was mutated. In cells, M1 alone was mainly observed in the nucleus (47%) and in the cytosol (42%). Conversely, when co-expressed with the viral proteins NS1/NEP and M2, M1 was relocated to the cell membranes (55%), as shown by subcellular fractionation experiments. This minimal system allowed the production of M1 containing-VLPs. However, M1 with mutations in the arginine triplet accumulated in intracellular clusters and its incorporation in VLPs was strongly diminished. M2 over-expression was essential for M1 membrane localization and VLP production, whereas the viral trans-membrane proteins HA and NA seemed dispensable. These results suggest that the M1 arginine triplet participates in M1 interaction with membranes. This R76/77/78 motif is essential for M1 incorporation in virus particles and the importance of this motif was confirmed by reverse genetic demonstrating that its mutation is lethal for the virus. These results highlight the molecular

  15. The human Müller cell line MIO-M1 expresses opsins.

    Science.gov (United States)

    Hollborn, Margrit; Ulbricht, Elke; Rillich, Katja; Dukic-Stefanovic, Sladjana; Wurm, Antje; Wagner, Lysann; Reichenbach, Andreas; Wiedemann, Peter; Limb, Gloria Astrid; Bringmann, Andreas; Kohen, Leon

    2011-01-01

    To determine whether the human Müller cell line Moorfields/Institute of Ophthalmology-Müller 1 (MIO-M1) expresses opsins. The gene expression of opsins was determined by reverse-transcription PCR (RT-PCR). The presence of opsin proteins was determined by western blotting and immunocytochemistry. The light sensitivity of the cells was examined with imaging experiments using the calcium-sensitive dye Fluo-4. MIO-M1 cells express glial (glutamine synthase [GLUL], vimentin [VIM], glial fibrillary acidic protein [GFAP], cellular retinaldehyde-binding protein [RLBP1], glial high-affinity glutamate transporter [SLCA1], aquaporin-4 [AQP4], inwardly rectifying potassium channel Kir4.1 [Kir4.1]), neuronal (Thy-1 cell surface antigen [THY1], heavy neurofilament polypeptide [NEFH], microtubule-associated protein 2 [MAP2], neurogenic differentiation 1 [NEUROD1], neuronal nuclei [NEUN]), and neural progenitor markers (Nestin [NES], paired-type homeobox transcription factor [PAX6], neurogenic locus notch homolog 1 [NOTCH1]). The cells contain mRNA for the following opsins: blue opsin (OPN1SW), rhodopsin (OPN2), panopsin (OPN3), melanopsin (OPN4), neuropsin (OPN5), and peropsin (RRH), as well as for the transducins (guanine nucleotide binding protein [GNAZ], alpha transducing activity polypeptide 1 [GNAT1], alpha transducing activity polypeptide 2 [GNAT2]). The presence of blue opsin and melanopsin was confirmed with immunocytochemistry and western blotting. The immunoreactivity and mRNA of red-green opsin were found in some but not all cultures, while the immunoreactivity for rhodopsin was absent in all cultures investigated. Repetitive stimulation with 480 nm light evoked slow and fast transient calcium responses in the majority of cells investigated, while irradiation with 600 nm light was ineffective. The human Müller cell line MIO-M1 expresses opsins. This suggests immortalized Müller cells could be used as a cellular source to produce human opsins for their potential

  16. Irreducible Modular Representations of the Reflection Group G(m,1,n

    Directory of Open Access Journals (Sweden)

    José O. Araujo

    2015-01-01

    Full Text Available In an article published in 1980, Farahat and Peel realized the irreducible modular representations of the symmetric group. One year later, Al-Aamily, Morris, and Peel constructed the irreducible modular representations for a Weyl group of type Bn. In both cases, combinatorial methods were used. Almost twenty years later, using a geometric construction based on the ideas of Macdonald, first Aguado and Araujo and then Araujo, Bigeón, and Gamondi also realized the irreducible modular representations for the Weyl groups of types An and Bn. In this paper, we extend the geometric construction based on the ideas of Macdonald to realize the irreducible modular representations of the complex reflection group of type G(m,1,n.

  17. 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.

  18. Occurrence of aflatoxin M(1) in dairy products in southern Italy.

    Science.gov (United States)

    Montagna, Maria Teresa; Napoli, Christian; De Giglio, Osvalda; Iatta, Roberta; Barbuti, Giovanna

    2008-12-01

    A screening survey of the presence of aflatoxin M(1) (AFM(1)) 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. AFM(1) 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 AFM(1) 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 AFM(1) threshold limits for dairy products is still lacking.

  19. Excretion of Aflatoxin M1 in milk of goats fed diet contaminated by Aflatoxin B1

    Directory of Open Access Journals (Sweden)

    Gianni Battacone

    2010-01-01

    Full Text Available An experiment was carried out to study the excretion of aflatoxin M1(AFM1 in milk of three goats fed a single dose (0.8mg/head of pure aflatoxin B1 (AFB1. The values of AFM1 concentration excreted in milk was highly variable among goats, even if the pattern of excretion over time was very similar among the three animals. AFM1 was first detected at the milking performed 1h after the AFB1 administration. The highest values of AFM1 concentration in milk were reached 3 and 6h after the AFB1 intake. The trend of clearance of AFM1 in milk over time was expressed by a decreasing exponential equation. AFM1 concentration was below the EU maximum allowed level (50 ng/L in milk collected 36 h after the AFB1 administration.

  20. Robinson-Schensted-Knuth Correspondence and Weak Polynomial Identities of M1,1(E)

    Institute of Scientific and Technical Information of China (English)

    Onofrio Mario Di Vincenzo; Roberto La Scala

    2005-01-01

    In this paper, it is proved that the ideal Iω of the weak polynomial identities of the superalgebra M1,1(E) is generated by the p roper polynomials [x1,x2, x3] and [x2,x1][xa,x1][x4, x1]. This is proved for any infinite field F of characteristic different a basis and the dimension of any multihomogeneous component of the quotient algebra B/(B ∩ Iw). We also compute the Hilbert series of this algebra. One of the main tools of this paper is a variant we found of the Robinson-Schensted-Knuth correspondence defined for single semistandard tableaux of double shape.

  1. Solvent affects the conformation of virginiamycin M1 (pristinamycin IIA, streptogramin A).

    Science.gov (United States)

    Dang, Jason; Bergdahl, Mikael; Separovic, Frances; Brownlee, Robert T C; Metzger, Robert P

    2004-10-21

    The streptogramins are antibiotics which act by binding two different components at separate nearby sites on the bacterial 50S ribosome, inhibiting protein synthesis. The first component, a macrolactone, is common to many of the streptogramin antibiotics and, thus, is referred to by many names including virginiamycin M1(VM1), pristinamycin IIA, ostreogrycin A and streptogramin A. X-Ray crystallographic studies of VM1 bound to ribosomes and to a deactivating enzyme show a different conformation to that of VM1 in chloroform solution. We now report the results of high resolution 2D NMR experiments that show that the conformation of VM1 in dimethyl sulfoxide and methanol differs from both that in chloroform solution and in the bound form. The 3D structure and the 1H NMR and 13C NMR chemical shifts of VM1 in dimethyl sulfoxide and methanol are described.

  2. RAPD Analysis of M1 Generation of Gladiolus hybridus Hort Treated by EMS

    Institute of Scientific and Technical Information of China (English)

    WANG Jingang; GUO Ying; CHE Daidi; LIU Shenkui; YANG Chuanpin

    2009-01-01

    Gladiolus hybridus Hort is one of the world's famous cutting flowers. It is very popular because of the big size, bright color, various shape, and long period of bloom. New species should be cultivated in order to meet the consumers' need of asking for the new. Among the technologies of cultivating new species of flowers, mutagenic breeding is a shortcut. This study treated corm bud of G. hybridus Hort with EMS of different consistency. Then M1 after treated was analyzed by RAPD. The result showed that EMS was a very effective mutagenic agent for the corm bud of G. hybridus Hort. With the increase of consistency, the mutagenic range increased first, then decreased, among which 0.6% EMS treatment had the biggest influence. However, with the same EMS consistency, there was not close relevancy between the amount of mutagenic agent and the divergence of plant's genomes, which offered a molecular basis for selecting plants with good mutation.

  3. 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.

  4. 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.

  5. The M/M/1 Queue with Controlled Multiple Working Vacations

    Institute of Scientific and Technical Information of China (English)

    ZHANG Hong-bo; FENG Ping-hua

    2013-01-01

    In this paper,we study an M/M/1 queue with multiple working vacations under following Bernoulli control policy:at the instants of the completion of a service in vacation,the server will interrupt the vacation and enter regular busy period with probabiiity1-p (if there are customers in the queue) or continue the vacation with probability p.For this model,we drive the analytic expression of the stationary queue length and demonstrate stochastic decomposition structures of the stationary queue length and waiting time,also we obtain the additional queue length and the additional delay of this model.The results we got agree with the corresponding results for working vacation model with or without vacation interruption if we set p =0 or p =1,respectively.

  6. Detection of Aflatoxin M1 in Milk from Qom (Aried and Semiaried Province of Iran

    Directory of Open Access Journals (Sweden)

    Mohammad Dakhili

    2016-06-01

    Full Text Available Background: Aflatoxins are secondary metabolites fungal When animals consume contaminated feed stuff to Aflatoxin B1 (AFB1, the toxin hydrolyzed and changed to the aflatoxin M1 and transmit to the milk consumers. Methods: seventy milk samples from different milk producers who were selling their milk to the dairy plant during two season in winter and summer and investigated by Enzyme Linked Immuno Sorbent Assay (ELISA. Results: AFM1 was found in 100% of the milk samples in winter. About 15% of the samples had AFM1 greater than the maximum tolerance limit (50ng/l accepted by European Union. Mean concentrations of AFM1 in Winter, Summer were 122, 53 ng/L, respectively. Mean concentrations of AFM1 in winter and Summer samples were significantly higher (P<0.05. Conclusion: these results show that the important of periodically monitoring the occurrence of AFM1 in raw milk and dairy products in Qom province.

  7. Fluid queues driven by an M/M/1/N queue

    Directory of Open Access Journals (Sweden)

    R. B. Lenin

    2000-01-01

    Full Text Available In this paper, we consider fluid queue models with infinite buffer capacity which receives and releases fluid at variable rates in such a way that the net input rate of fluid into the buffer (which is negative when fluid is flowing out of the buffer is uniquely determined by the number of customers in an M/M/1/N queue model (that is, the fluid queue is driven by this Markovian queue with constant arrival and service rates. We use some interesting identities of tridiagonal determinants to find analytically the eigenvalues of the underlying tridiagonal matrix and hence the distribution function of the buffer occupancy. For specific cases, we verify the results available in the literature.

  8. Scaled-energy spectroscopy of a |M|=1 Rydberg barium atom in an electric field

    Institute of Scientific and Technical Information of China (English)

    Wang Lei; Quan Wei; Shen Li; Yang Hai-Feng; Shi Ting-Yun; Liu Xiao-Jun; Liu Hong-Ping; Zhan Ming-Sheng

    2009-01-01

    We observe strong energy-dependent quantum defects in the scaled-energy Stark spectra for |M|=1 Rydberg states of barium atoms at three scaled energies: ε= -2.000, ε= -2.500 and ε=-3.000. In an attempt to explain the observations, theoretical calculations of closed orbit theory based on a model potential including core effect are performed for non-hydrogenic atoms. While such a potential has been uniformly successful for alkali atoms with a single valence electron, it fails to match experimental results for barium atoms in the 6snp Rydberg states with two valence electrons. Our study points out that this discrepancy is due to the strong perturbation from the 5d8p state, which voids the simple approximation for constant quantum defects of principle quantum number n.

  9. E1M1 and E1E2 transition probabilities in one-electron ions

    Energy Technology Data Exchange (ETDEWEB)

    Labzowsky, L.N. [Institute of Physics, St. Petersburg State University, Uljanovskaya 1, Petrodvorets, 198904 St. Petersburg (Russian Federation) and Petersburg Nuclear Physics Institute, Gatchina, 188350 St. Petersburg (Russian Federation)]. E-mail: leonti@landau.phys.spbu.ru; Shonin, A.V. [Institute of Physics, St. Petersburg State University, Uljanovskaya 1, Petrodvorets, 198904 St. Petersburg (Russian Federation)

    2004-12-06

    The quantum electrodynamical (QED) theory of the two-photon transitions in hydrogenlike ions is presented. The emission probability for 2s1/2->2{gamma}(E1)+1s1/2 transitions is calculated and compared to the results of the previous calculations. The emission probabilities 2p1/2->{gamma}(E1)+{gamma}(E2)+1s1/2 and 2p1/2->{gamma}(E1)+{gamma}(M1)+1s1/2 are also calculated for the nuclear charge Z values 1=

  10. Remarks on the BRST-cohomology for $c_M > 1$ matter coupled to ``Liouville gravity"

    CERN Document Server

    Bilal, Adel

    1992-01-01

    We describe the (chiral) BRST-cohomology of matter with central charge $10$) and ghost-numbers 0 or $-1$ (for $r<0$). The (chiral) ground ring is isomorphic to a subring of the $c_M =1$ theory which is $(xy)^n,\\ n=0,1,2,\\ldots$, and there are {\\it no} non-trivial currents acting on the ground ring. In case b) there is no non-trivial relative cohomology for non-zero ghost numbers and, for zero ghost number, the cohomology groups are isomorphic to a $(D-1)$-dimensional on-shell ``transverse" Fock space. The only exceptions are at level 1 for vanishing matter momentum and $p_L=Q_L(1+r)$ with $r=\\pm 1$, where one has one more ghost-number zero and a ghost-number $r$ cohomology state. All these results follow quite easily from the existing literature.

  11. BRST cohomology ring in $\\widehat{c}_{M}$ $<$ 1 NSR string theory

    CERN Document Server

    Panda, S; Panda, Sudhakar; Roy, Shibaji

    1995-01-01

    The full cohomology ring of the Lian-Zuckerman type operators (states) in {\\hat c_M}<1 Neveu-Schwarz-Ramond (NSR) string theory is argued to be generated by three elements x, y and w in analogy with the corresponding results in the bosonic case. The ground ring generators x and y are non-invertible and belong to the Ramond sector whereas the higher ghost number operators are generated by an invertible element w with ghost number one less than that of the ground ring generators and belongs to either Neveu-Schwarz (NS) or Ramond (R) sector depending on whether we consider (even, even) or (odd, odd) series coupled to 2d supergravity. We explicitly construct these operators (states) and illustrate our result with an example of pure Liouville supergravity.

  12. The Matrix protein M1 from influenza C virus induces tubular membrane invaginations in an in vitro cell membrane model

    Science.gov (United States)

    Saletti, David; Radzimanowski, Jens; Effantin, Gregory; Midtvedt, Daniel; Mangenot, Stéphanie; Weissenhorn, Winfried; Bassereau, Patricia; Bally, Marta

    2017-01-01

    Matrix proteins from enveloped viruses play an important role in budding and stabilizing virus particles. In order to assess the role of the matrix protein M1 from influenza C virus (M1-C) in plasma membrane deformation, we have combined structural and in vitro reconstitution experiments with model membranes. We present the crystal structure of the N-terminal domain of M1-C and show by Small Angle X-Ray Scattering analysis that full-length M1-C folds into an elongated structure that associates laterally into ring-like or filamentous polymers. Using negatively charged giant unilamellar vesicles (GUVs), we demonstrate that M1-C full-length binds to and induces inward budding of membrane tubules with diameters that resemble the diameter of viruses. Membrane tubule formation requires the C-terminal domain of M1-C, corroborating its essential role for M1-C polymerization. Our results indicate that M1-C assembly on membranes constitutes the driving force for budding and suggest that M1-C plays a key role in facilitating viral egress. PMID:28120862

  13. Sequence Characterization of matrix protein (M1 in influenza A viruses (H1, H3 and H5

    Directory of Open Access Journals (Sweden)

    Jun Zhang

    2011-10-01

    Full Text Available This study brings the analysis of amino acid sequences of matrix protein (M1 from the influenza virus A (H1N1, H3N2 and H5N1 during 2007-2208. 741 sequences of M1 were compared, of them, H1N1 388; H3N2 251 and H5N1 102. Even though, the M1 is relatively conserved among the influenza A viruses, we found some variations in the M1 among the viruses, H1N1, H3N2 and H5N1. The nuclear localization signal at amino acid 101 to 105 is RKLKR for H1N1 and H3N2, but for H5N1 is KKLKR. All differences of amino acid in M1 of H1, H3 and H5 were listed. 80 sequences of M1 of H1N1 H3N2 and H5N1 were used for phylogenetic analysis. There is no reasontantment found in the M1 among these subtypes. Further study is needed to study the differences of the function of M1 among H1N1, H3N2 and H5N1. The M1 of H5N1 may contribute to the high pathogenesis to this virus.

  14. Seasonal milk contamination by aflatoxin m1, organophosphates and carbamates in Paraná – Brazil

    Directory of Open Access Journals (Sweden)

    Carlos Eduardo Crispim de Oliveira Ramos

    2016-08-01

    Full Text Available Aiming to evaluate the milk contamination in the dairy production systems (DPS for mycotoxins and chemical residues of organophosphates and carbamates it was made a study encompassing 96 DPS in three regions of Parana state. There were collected samples of milk, water and food and they were evaluated for chemical residues in all samples and aflatoxin only for food and milk. Mycotoxins in food (aflatoxin B1, B2, G1, G2, zearalenone and ochratoxin were detected by the method of thin layer chromatography – TLC and for the determination of aflatoxin M1 was used an immunoassay kit competitive ELISA Ridascreen®. The residues of organophosphates and carbamates were performed by colorimetric method qualitatively. There were evaluated the differences between regions, periods and the sources of mycotoxin contamination. Carbamates and organophosphates were screened for their presence in milk and the sources of food and water. Then it was estimated the contributions of each mycotoxin for milk contamination, as well as their respective contaminated food. Differences were found between periods (p < 0,05 for milk contamination with aflatoxin M1 – AFM1. For carbamates and organophosphates were found different contamination sources (p < 0,01. For the carbamates the source were pesticides used to parasitic herd control and for the organophosphates pesticides used in agriculture. For food sources contamination resulting in the AFM1 contamination it was detected that aflatoxin B1 – AFB1 was the main source. The aflatoxin G1 – AFG1 showed a strong correlation (p < 0,01 with AFB1 levels suggesting causal relationship is a function of fungal strains producing both at the same time. It was also found the prevalence of aflatoxin contamination in 70% of contaminated samples and its predominant presence in relation to other mycotoxins in all kinds of foods analyzed. By identifying the checkpoints of contamination can be proposed the inclusion of practical

  15. 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.

  16. 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

  17. The M1 muscarinic antagonist pirenzepine reduces myopia and eye enlargement in the tree shrew.

    Science.gov (United States)

    Cottriall, C L; McBrien, N A

    1996-06-01

    To determine the efficacy of the M1-selective muscarinic antagonist, pirenzepine, in preventing experimentally induced myopia in a mammalian model, the tree shrew. Tree shrews were monocularly deprived (MD) using translucent goggles or negative lenses for a period of 12 days. In two of the MD groups, tree shrews received daily subconjunctival administration of either pirenzepine (17.7 mumol; n = 9) or vehicle control (n = 6). Control groups (n = 6) were used to assess the effects of MD, injection regimen, and drug effects. In sham-injected and saline-injected MD tree shrews, 12 days of MD produced-13.2 D +/- 0.8 D and -14.1 D +/- 0.5 D of axial myopia, respectively. In pirenzepine-injected MD tree shrews, 12 days of MD induced an axial myopia of only -2.1 D +/- 1.4 D. The significant reduction in myopia in pirenzepine-injected MD tree shrews was caused by significantly less vitreous chamber elongation of the deprived eye (0.05 mm +/- 0.04 mm) relative to the contralateral control eye when compared to sham-injected and saline-injected MD tree shrews (0.24 mm +/- 0.02 mm and 0.29 mm +/- 0.01 mm). Mean equatorial enlargement and increased eye weight were prevented in pirenzepine-injected MD tree shrews (P Pirenzepine also was found to reduce myopia and ocular enlargement in lens defocus-induced myopia. Control experiments demonstrated that pirenzepine did not cause a significant reduction in amplitude of carbachol-induced accommodation. Findings demonstrate that chronic administration of the M1-selective muscarinic antagonist, pirenzepine, prevents experimentally induced myopia in this mammalian model by a nonaccommodative mechanism.

  18. Paracoccin Induces M1 Polarization of Macrophages via Interaction with TLR4

    Science.gov (United States)

    Freitas, Mateus S.; Oliveira, Aline F.; da Silva, Thiago A.; Fernandes, Fabrício F.; Gonçales, Relber A.; Almeida, Fausto; Roque-Barreira, Maria C.

    2016-01-01

    The fungal human pathogen Paracoccidioides brasiliensis contains paracoccin (PCN), a multi-domain protein that has lectin and N-acetyl-glucosaminidase activities, which account for its effects on the growth and morphogenesis of the fungus and on the activation of host macrophages through its interaction with TLR N-glycans. With the purpose of detailing the knowledge on the effects of PCN on macrophages, we used recombinant PCN expressed in Pichia pastoris (p-rPCN) to stimulate isolated murine peritoneal macrophages. The activation of these cells manifested through the release of high levels of inflammatory mediators, such as nitric oxide, TNF-α, IL-12p40, and IL-6. Furthermore, peritoneal macrophages stimulated with p-rPCN increased the relative expression of STAT1, SOCS3, and iNOS2 mRNA (M1 polarization markers). However, the expression of Arginase-1, Ym-1, and FIZZ1 (M2 polarization markers) remained at basal levels. Interestingly, the observed M1 macrophages’ polarization triggered by p-rPCN was abolished in cells obtained from knockout Toll-like receptor-4 mice. In this case, the p-rPCN-induced production of pro-inflammatory mediators was blocked too. These results demonstrate that the classical activation of macrophages induced by paracoccin depends on TLR4. Taken together, the results of our study indicate that paracoccin acts as a TLR agonist able to modulate immunity and exerts biological activities that favor its applicability as an immunotherapeutic agent to combat systemic fungal infections. PMID:27458431

  19. Composition of breccia matrices from the Manson M-1 drill core

    Science.gov (United States)

    Kracher, A.; Anderson, R. R.; Koeberl, C.

    1994-07-01

    Eleven drill cores were recently recovered from the Manson, Iowa, impact structure. Core M-1, which was drilled at the edge of the large central uplift, contains three major impact rock types: sedimentary clast breccia, melt matrix breccia, and fragmental breccia. Breccia matrices from different depths in the M-1 core were investigated by defocused beam electron probe microanalysis. To obtain average compositions, matrix areas free of lithic and mineral clasts were covered with an orthogonal grid of analyses points. Variations in composition have two main causes: differences in source lithology and postimpact processes. With increasing depth distinct changes in composition can be observed. All compositions are highly feldspathic and surprisingly low in SiO2 for putative source lithologies of mostly granitic composition. Within the lithological units containing melt matrix breccia increasing recrystallization can be observed with depth. Compositions in this interval are marginally corundum normative and not as high in normative feldspar as other matrices. The thoroughly recrystallized matrices from the lowest intervals of the melt matrix breccia are more feldpathic, higher in Na/K ratio, and not corundum normative. Unlike the chemical variation between rock types, we tentatively ascribe the chemical changes within the melt matrix breccia to reaction of matrix with clasts. In particular, quartz clasts in breccias with highly recrystallized matrices develop fringes of K-spar, cpx, and ilmenite. The formation of these minerals is presumably accompanied by complementary changes in matrix composition. Factor analysis on data sets of individual melt matrix analyses provides further clues to the influence of source lithology and post impact processes respectively in the chemical makeup of the breccia matrices. The most significant factors are a mafic component and a plagioclase component.

  20. Distant and new mutations in CTX-M-1 beta-lactamase affect cefotaxime hydrolysis.

    Science.gov (United States)

    Pérez-Llarena, Francisco José; Kerff, Frédéric; Abián, Olga; Mallo, Susana; Fernández, María Carmen; Galleni, Moreno; Sancho, Javier; Bou, Germán

    2011-09-01

    The CTX-M β-lactamases are an increasingly prevalent group of extended-spectrum β-lactamases (ESBL). Point mutations in CTX-M β-lactamases are considered critical for enhanced hydrolysis of cefotaxime. In order to clarify the structural determinants of the activity against cefotaxime in CTX-M β-lactamases, screening for random mutations was carried out to search for decreased activity against cefotaxime, with the CTX-M-1 gene as a model. Thirteen single mutants with a considerable reduction in cefotaxime MICs were selected for biochemical and stability studies. The 13 mutated genes of the CTX-M-1 β-lactamase were expressed, and the proteins were purified for kinetic studies against cephalothin and cefotaxime (as the main antibiotics). Some of the positions, such as Val103Asp, Asn104Asp, Asn106Lys, and Pro107Ser, are located in the (103)VNYN(106) loop, which had been described as important in cefotaxime hydrolysis, although this has not been experimentally confirmed. There are four mutations located close to catalytic residues-Thr71Ile, Met135Ile, Arg164His, and Asn244Asp-that may affect the positioning of these residues. We show here that some distant mutations, such as Ala219Val, are critical for cefotaxime hydrolysis and highlight the role of this loop at the top of the active site. Other distant substitutions, such as Val80Ala, Arg191, Ala247Ser, and Val260Leu, are in hydrophobic cores and may affect the dynamics and flexibility of the enzyme. We describe here, in conclusion, new residues involved in cefotaxime hydrolysis in CTX-M β-lactamases, five of which are in positions distant from the catalytic center.

  1. 乳品中黄曲霉毒素M1检测方法研究进展%Review on detection methods of aflatoxin M1 in dairy products

    Institute of Scientific and Technical Information of China (English)

    黄亚伟; 魏光; 王若兰; 罗莉

    2014-01-01

    Aflatoxin M1 is the metabolite of aflatoxin B1 after being intaken by animals. It mainly appears in animals’ milk and urine. Aflatoxin M1 is very toxic, ingestion of which by dairy will produce a great harm to the human body. This paper focused on the toxicity, hazards, and detection methods of aflatoxin M1 in dairy. The main characteristics and scope of the detection methods were analyzed and summarized, and the develop-ment of detection of aflatoxin M1 were also reasonably prospected.%黄曲霉毒素M1是动物摄入黄曲霉毒素B1后的代谢产物,主要分布在动物的乳汁、尿液中。黄曲霉毒素 M1毒性很大,经乳制品摄入会对人体产生巨大的危害。本文主要对乳品中黄曲霉毒素 M1毒性、危害、检测方法进行综述。对主要检测方法的特性及适用范围进行分析与概括,并且对未来黄曲霉毒素M1的检测方法的发展进行了合理展望。

  2. 叉头框蛋白 M1在乳腺癌的进展及治疗耐药中的作用%The role of FoxM1 in the development and treatment of breast cancer

    Institute of Scientific and Technical Information of China (English)

    李蕙颖(综述); 耿敬姝(审校)

    2016-01-01

    FoxM1 is a specific transcription factor related to proliferation .Previous studies have found that FoxM1 can enhance the proliferation ,metastasis and invasion of cancer cells ,and play a crucial role in canc-er.Recent studies indicate that the abnormal expression of FoxM 1 plays an important role in breast cancer ,and its overexpression is negatively correlated with the overall survival of patients .For the early diagnosis of breast canc-er,clinical prognosis and study on combination therapy provides a new direction .This article reviews the relation-ship between FoxM1 and breast cancer .%叉头框蛋白质M1(Forkhead box protein M1,FoxM1)是一种特异性的与增殖相关的转录因子。既往研究发现,FoxM1具有增强癌细胞增殖、转移和侵袭的功能,在肿瘤的发生发展中扮演着至关重要的角色。近年来研究表明,FoxM1的异常表达在乳腺癌的发生及发展中起着重要的作用,且其过表达与肿瘤患者的总生存期的关系呈负相关,为乳腺癌的早期诊断、临床预后及联合治疗提供了新的研究方向,本文就FoxM1与乳腺癌的关系做一综述。

  3. The preparation of milkpowder contaminated with aflatoxin M1. Investigations of the homogeneity and stability of the product

    NARCIS (Netherlands)

    Egmond; H.P.van; Sizoo; E.A.

    1984-01-01

    Ten behoeve van BCR werd een hoeveelheid melkpoeder bereid, langs natuurlijke weg besmet met aflatoxine M1 op een niveau van ca. 1 mug/kg. Onderzoek naar de homogeniteit van het materiaal wees uit dat aflatoxine M1 homogeen verdeeld was over de geproduceerde melkpoeder. Voorts bleek dat beware

  4. Nuclear export of the influenza virus ribonucleoprotein complex: Interaction of Hsc70 with viral proteins M1 and NS2.

    Science.gov (United States)

    Watanabe, Ken; Shimizu, Teppei; Noda, Saiko; Tsukahara, Fujiko; Maru, Yoshiro; Kobayashi, Nobuyuki

    2014-01-01

    The influenza virus replicates in the host cell nucleus, and the progeny viral ribonucleoprotein complex (vRNP) is exported to the cytoplasm prior to maturation. NS2 has a nuclear export signal that mediates the nuclear export of vRNP by the vRNP-M1-NS2 complex. We previously reported that the heat shock cognate 70 (Hsc70) protein binds to M1 protein and mediates vRNP export. However, the interactions among M1, NS2, and Hsc70 are poorly understood. In the present study, we demonstrate that Hsc70 interacts with M1 more strongly than with NS2 and competes with NS2 for M1 binding, suggesting an important role of Hsc70 in the nuclear export of vRNP.

  5. F-box protein FBXL2 inhibits gastric cancer proliferation by ubiquitin-mediated degradation of forkhead box M1.

    Science.gov (United States)

    Li, Liang-qing; Pan, Dun; Chen, Hui; Zhang, Lin; Xie, Wen-jun

    2016-02-01

    F-box/LRR-repeat protein 2 (FBXL2), a component of Skp-Cullin-F box (SCF) ubiquitin E3 ligase, has been shown to inhibit tumorigenesis by targeting and ubiquitinating several oncoproteins. However, its role in gastric cancer remains poorly understood. Here, by tandem mass spectrometry, we show that FBXL2 interacts with forkhead box M1 (FoxM1) transcription factor. As a result, FBXL2 promotes ubiquitination and degradation of FoxM1 in gastric cancer cells. Furthermore, overexpression of FBXL2 inhibits, while its deficiency promotes cell proliferation and invasion. Expression levels of cell-cycle regulators (Cdc25B and p27), which are down-stream target effectors of FoxM1, are also regulated by FBXL2. Therefore, our results uncover a previous unknown network involving FBXL2 and FoxM1 in the regulation of gastric cancer growth.

  6. Targeting Rac1 signaling inhibits streptococcal M1 protein-induced CXC chemokine formation, neutrophil infiltration and lung injury.

    Directory of Open Access Journals (Sweden)

    Songen Zhang

    Full Text Available Infections with Streptococcus pyogenes exhibit a wide spectrum of infections ranging from mild pharyngitis to severe Streptococcal toxic shock syndrome (STSS. The M1 serotype of Streptococcus pyogenes is most commonly associated with STSS. In the present study, we hypothesized that Rac1 signaling might regulate M1 protein-induced lung injury. We studied the effect of a Rac1 inhibitor (NSC23766 on M1 protein-provoked pulmonary injury. Male C57BL/6 mice received NSC23766 prior to M1 protein challenge. Bronchoalveolar fluid and lung tissue were harvested for quantification of neutrophil recruitment, edema and CXC chemokine formation. Neutrophil expression of Mac-1 was quantified by use of flow cytometry. Quantitative RT-PCR was used to determine gene expression of CXC chemokines in alveolar macrophages. Treatment with NSC23766 decreased M1 protein-induced neutrophil infiltration, edema formation and tissue injury in the lung. M1 protein challenge markedly enhanced Mac-1 expression on neutrophils and CXC chemokine levels in the lung. Inhibition of Rac1 activity had no effect on M1 protein-induced expression of Mac-1 on neutrophils. However, Rac1 inhibition markedly decreased M1 protein-evoked formation of CXC chemokines in the lung. Moreover, NSC23766 completely inhibited M1 protein-provoked gene expression of CXC chemokines in alveolar macrophages. We conclude that these novel results suggest that Rac1 signaling is a significant regulator of neutrophil infiltration and CXC chemokine production in the lung. Thus, targeting Rac1 activity might be a potent strategy to attenuate streptococcal M1 protein-triggered acute lung damage.

  7. 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.

  8. 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.

  9. Dose Measurements on the BION-M1 satellite applying passive detector packages

    Science.gov (United States)

    Stradi, Andrea; Berger, Thomas; Kodaira, Satoshi; Kubancak, Jan; Palfalvi, Jozsef K.; Ambrozova, Iva; Tolochek, Raisa; Shurshakov, Vyacheslav; Szabo, Julianna

    A passive detector package was developed in the past years in the Centre for Energy Research, Hungarian Academy of Science to detect cosmic ray particles, to determine their flux and dose. It consists of thermoluminescent detectors (TLD) and plastic solid state nuclear track detectors (SSNTD). In the frame of a scientific co-operation between the Institute for Biomedical Problems (IBMP) fourteen packages were flow within the new BION-M1 satellite program together with biological samples and detector packages from other participants. Two packages were located outside and the rest ones inside the recoverable capsule. Comparing to the previous BION and similar FOTON experiments, (all together 17 successful ones), this flight was a “champion” with the highest altitude (575 km), orbital inclination (64.9°) and flight duration (30 days). The external exposure provided a unique possibility to study not only the elevated level of cosmic rays but also the behavior of the detector packages in extreme circumstances as low temperature and pressure. The paper will summarize the construction of the detector packages, the calibration and evaluation processes, as well as, the linear energy transfer (LET) spectra, the absorbed dose and the mean quality factor. These quantities will be compared taking into consideration their location inside and outside the capsule and to the results of other participants. Also some comparison of results to the previous BION and FOTON flights and contemporary measurements on the ISS will be presented.

  10. 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.

  11. DETECTION OF AFLATOXIN M1 IN BULK-TANK MILK AND SHEEP CHEESE

    Directory of Open Access Journals (Sweden)

    F. Cossu

    2011-01-01

    Full Text Available The Aflatoxin M1 (AFM1 content in 118 bulk-tank sheep milk samples was evaluated using an ELISA commercial kit. During a lactation, three bulk-tank milk samples were collected from each of 40 semi-extensive farms, selected on the basis of high level of concentrate supplementation as risk factor for exposure to Aflatoxin B1 (AFB1. The AFM1 content was also determined in 38 sheep cheese samples collected from a dairy plant where the farms enrolled in the survey shipped the milk. In the three sampling the concentrate supplementation recorded in the farms ranged between (mean±sd 492.2±257.7 and 397.7±214.3. AFM1 was detected in 1 bulk-tank sheep milk sample (0.8% at concentrations as little as 5.2 ng/L while in 117 it was not detectable (<5 ng/L. AFM1 was also detected in 5 (13.2% out of 38 samples of ripened sheep cheese at levels (mean±sd of 58.1±7.8 ng/Kg. A very low AFM1 content in bulk mik and cheese was observed, as the result of the implementation of good agricultural and good farming practices.

  12. Enhanced spectrofluorimetric determination of aflatoxin M1 in liquid milk after magnetic solid phase extraction

    Science.gov (United States)

    Hashemi, Mahdi; Taherimaslak, Zohreh; Rashidi, Somayeh

    2014-07-01

    A simple and sensitive method using magnetic solid phase extraction (MSPE) followed by spectrofluorimetric detection has been developed for separation and determination of aflatoxin M1 (AFM1) in liquid milk. The method is based on the extraction of AFM1 on the modified magnetic nanoparticles (MMNPs) and subsequent derivatization of extracted AFM1 to AFM1 hemi-acetal derivative (AFM2a) by reaction with trifluoroacetic acid (TFA) for spectrofluorimetric detection. Magnetic nanoparticles (MNPs) coated by 3-(trimethoxysilyl)-1-propantiol (TMSPT) and modified with 2-amino-5-mercapto-1,3,4-thiadiazole (AMT) were used as adsorbent in MSPE procedure. Influential parameters affecting the extraction efficiency were investigated and optimized. Under the optimum conditions the calibration curve for AFM1 determination showed good linearity in the range 0.030-10.0 μg L-1 (R2 = 0.9991). The repeatability and reproducibility (RSD%) for 0.050 μg L-1 of AFM1 were 4.5% and 5.3%, respectively and limit of detection limit (S/N = 3) was estimated to be 0.010 μg L-1. The developed method was successfully applied for extraction of AFM1 from spiked liquid milk and natural contaminated liquid milk. The good spiked recoveries ranging from 91.6% to 96.1% were obtained. The results demonstrated that the developed method is simple, inexpensive, accurate and remarkably free from interference effects.

  13. Microwave Emission of Supra-arcade Structure associated with M1.6 Limb Flare

    CERN Document Server

    Kim, Sujin; Shibasaki, Kiyoto; Reznikova, Veronika

    2012-01-01

    We have investigated a supra-arcade structure, associated with an M1.6 flare, which occurred on the south-east limb on 4th of November 2010. It is observed in microwaves at 17 GHz with the Nobeyama Radioheliograph (NoRH), soft X-rays in the range of 8-20 keV with the Reuven Ramaty High Energy Solar Spectroscopic Imager (RHESSI), and EUV with the Atmospheric Imaging Assembly (AIA) onboard the Solar Dynamics Observatory (SDO). As reported by Reeves & Golub (2011), the supra-arcade structure is observed predominantly in the AIA 131 {\\AA} channel, which contains a hot 11 MK component from Fe XIX (Boerner et al. 2011). While this hot flare plasma lasts over the decay phase of the flare, it shows some interesting characteristics in microwaves and soft X-rays: 1) In the supra-arcade structure, the brightness temperature (TB) of the microwave emission increases gradually up to 2\\times10^4 K, and 2) two soft X-ray sources appear: one cospatial with the supra-arcade structure and another above the post-flare arcade...

  14. Green pigment from Bacillus cereus M(1)(16) (MTCC 5521): production parameters and antibacterial activity.

    Science.gov (United States)

    Banerjee, Debopam; Chatterjee, Sandipan; Banerjee, U C; Guha, Arun K; Ray, Lalitagauri

    2011-07-01

    A bacterial strain, Bacillus cereus M(1)(16) (MTCC 5521), isolated and identified in our laboratory produces a green pigment when grown in nutrient broth at stationary condition. Optimum fermentation parameters for maximum pigment production are pH 7.0, temperature 30°C, time of incubation 72 h and inoculum volume 1% from 20 h grown cell suspension. Magnesium ion enhances pigment production whereas calcium and zinc ions inhibit the process. The pigment is better extracted from the fermented broth with chloroform in comparison with diethyl ether, ethyl acetate, and butanol. The extracted crude pigment consists of three fractions as revealed from thin layer chromatogram on silica gel GF254 using ethyl acetate and hexane (1:1) solvent system. The major fraction C(3) shows antibacterial activity against different gram positive bacteria. The proposed structure of C(3) is 9-methyl-1,4,5,8-tetra-azaphenanthrene obtained by elemental analysis, GC-MS, and NMR spectra studies.

  15. Development of ultrasensitive direct chemiluminescent enzyme immunoassay for determination of aflatoxin M1 in milk.

    Science.gov (United States)

    Vdovenko, Marina M; Lu, Chuan-Chen; Yu, Feng-Yih; Sakharov, Ivan Yu

    2014-09-01

    A direct competitive chemiluminescent enzyme-linked immunosorbent assay (CL-ELISA) for detecting aflatoxin M1 (AFM1) was developed. To improve the sensitivity of the assay, a mixture of 3-(10'-phenothiazinyl)-propane-1-sulfonate (SPTZ) and 4-morpholinopyridine (MORPH) was used to enhance peroxidase-induced CL. The concentrations of the coating anti-AFM1 antibody and the conjugate of AFB1 with horseradish peroxidase the conditions of the chemiluminescent assay were varied to optimise the condition of the chemiluminescent assay. The lower detection limit values and dynamic working range of CL-ELISA of AFM1 were 0.001 ng mL(-1) and 0.002-0.0075 ng mL(-1), respectively. A 20-fold dilution of milk samples prevented a matrix effect of the milk and allowed measurement of AFM1 at concentrations below than the maximum acceptable limit. Values of recovery within and between assays were 81.5-117.6% and 86-110.6%, respectively. The results of using the developed CL-ELISA to analyse samples of six brands of milk that were purchased in Taiwan revealed that AFM1 was absent from all studied samples.

  16. Enzyme-assisted extraction for the HPLC determination of aflatoxin M1 in cheese.

    Science.gov (United States)

    Pietri, Amedeo; Fortunati, Paola; Mulazzi, Annalisa; Bertuzzi, Terenzio

    2016-02-01

    The extraction of aflatoxin M1 (AFM1) from cheese is generally carried out using chlorinated organic solvents. In this study, two innovative methods were developed, based on an enzyme-assisted (EA) extraction using proteolytic enzymes (pepsin or pepsin-pancreatin). After purification through an immunoaffinity column, AFM1 is determined by HPLC-FLD. A comparison between the new EA methods and an established chloroform (CH) method was carried out on 24 cheese samples. The results showed that the extraction efficiency of the EA methods was independent of ripening time of cheese, whereas the CH method was not able to fully recover AFM1 from ripened cheeses. The simpler (pepsin) of the two methods has been adopted by our laboratory for routine analysis of AFM1 in cheese. In comparison with the CH method, the pepsin-HCl (P-HCl) method is simpler, avoiding solvent evaporation, dissolution and partition in a separating funnel; moreover, it gives higher recoveries, comparable LOD and LOQ and more accurate results.

  17. Cloning and Expression of Bile Salt Hydrolase Gene from Lactobacillus plantarum M1-UVS29

    Institute of Scientific and Technical Information of China (English)

    Yu Chang-qing; Li Rong

    2015-01-01

    We cloned and expressed bile salt hydrolase gene ofLactobacillus plantarum M1-UVS29 inLactococcus lactis NZ9000 successfully. Gene-specific primers for amplification ofL. plantarum bsh were designed by using sequence which availabled from GenBank. The production of PCR amplicon was confirmed by sequencing and cloned into pMD18-T vector, and then recombined into expression vector pNZ8148 and yielding vector pNZ8148-BSH. pNZ8148-BSH was transferred intoLactococcus lactis NZ9000. Sequencing indicated that the clonedbsh fragment contained 995 nucleotides, and shared 99.3% sequence homology withbsh gene fromL. plantarum MBUL10. Clonedbsh fragment was successfully transduced into NICE expression system and confirmed by PCR and restriction digest. Recombinant BSH protein was analyzed by SDS-PAGE. The molecular weight of BSH protein was approximately 37 ku. Activity of the expressed protein was 0.77 µmol• min-1. The successfully expressed proteins by genetic engineering technology made the function of lactic acid bacteria be abundant and laid the foundation for further researches into cholesterol-lowering lactic acid bacterium food and probiotics.

  18. Indication for joint replacement and glutathione s-transferases M1 and T1 genotypes.

    Science.gov (United States)

    Klein, Torsten; Selinski, Silvia; Blaszkewicz, Meinolf; Hengstler, Jan G; Golka, Klaus

    2012-01-01

    In most patients with osteoarthritis (OA), therapy-resistant pain is the indication for hip or knee replacement. Glutathione S-transferases, particularly glutathione S-transferase M1 (GSTM1), are involved in metabolism of highly reactive metabolites that may be generated by inflammatory processes. In total, 148 patients with indication for hip or knee replacement and 129 patients of the same hospital without indication for joint replacement were genotyped for GSTM1 and GSTT1 and interviewed by a newly developed questionnaire for occupational and nonoccupational risk factors of hip and/or knee osteoarthritis. Mean age was 70.9 yr in OA cases and 67.4 yr in controls. The frequency of GSTM1 negative in the OA case group was (45%) in the lower range compared to values in Caucasian general population (approximately 50%), whereas the frequency in the controls was normal (51%). The frequency of GSTT1 negative genotype in OA cases and controls was normal. The normal distribution of the GSTM1 negative genotype in patients with indication for hip or knee replacement indicates that the role GSTM1 in these patients is different from that in other aseptic inflammatory diseases such as ozone-related inflammatory reactions of the respiratory tract.

  19. Miners compensated for pneumoconiosis and glutathione s-transferases M1 and T1 genotypes.

    Science.gov (United States)

    Zimmermann, Anna; Ebbinghaus, Rainer; Prager, Hans-Martin; Blaszkewicz, Meinolf; Hengstler, Jan G; Golka, Klaus

    2012-01-01

    Chronic inhalation of quartz-containing dust produces reversible inflammatory changes in lungs resulting in irreversible fibrotic changes termed pneumoconiosis. Due to the inflammatory process in the lungs, highly reactive substances are released that may be detoxified by glutathione S-transferases. Therefore, 90 hard coal miners with pneumoconiosis as a recognized occupational disease (in Germany: Berufskrankheit BK 4101) were genotyped for glutathione S-transferases M1 (GSTM1) and T1 (GSTT1) according to standard methods. Furthermore, occupational exposure and smoking habits were assessed by questionnaire. Changes in a chest x-ray were classified according to ILO classification 2000. Of the investigated hard coal miners 43% were GSTM1 negative whereas 57% were GSTM1 positive. The arithmetic mean of the age at time of investigation was 74.2 yr (range: 42-87 yr). Seventy-four percent of the hard coal miners reported being ever smokers, while 26% denied smoking. All hard coal miners provided pneumoconiosis-related changes in the chest x-ray. The observed frequency of GSTM1 negative hard coal miners was not different from frequencies reported for general Caucasian populations and in agreement with findings reported for Chinese coal miners. In contrast, in a former study, 16 of 19 German hard coal miners (84%) with urinary bladder cancer displayed a GSTM1 negative genotype. The outcome of this study provides evidence that severely occupationally exposed Caucasian hard coal miners do not present an elevated level of GSTM1 negative individuals.

  20. Purification and characterization of virginiamycin M1 reductase from Streptomyces virginiae.

    Science.gov (United States)

    Suzuki, N; Lee, C K; Nihira, T; Yamada, Y

    1998-11-01

    Virginiamycin M1 (VM1), produced by Streptomyces virginiae, is a polyunsaturated macrocyclic lactone antibiotic belonging to the virginiamycin A group. S. virginiae possesses an activity which stereospecifically reduces a 16-carbonyl group of VM1, resulting in antibiotically inactive 16R-dihydroVM1. The corresponding VM1 reductase was purified to homogeneity from crude extracts of S. virginiae in five steps, with 5,650-fold purification and 23% overall yield. The N-terminal amino acid sequence was determined to be MAIKLVIA. The purified enzyme showed an apparent Mr of 73,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and an Mr of 280,000 by native molecular sieve high-performance liquid chromatography, indicating the tetrameric nature of the native enzyme. NADPH served as a coenzyme for the reduction, with a Km value of 0.13 mM, but NADH did not support the reaction, even at a concentration of 5 mM, indicating the NADPH-specific nature of the enzyme. The Km for VM1 was determined to be 1.5 mM in the presence of 2 mM NADPH. In the reverse reaction, only 16R-dihydroVM1, not the 16S-epimer, served as a substrate, with a less than 0.1% overall reaction rate compared to that of the forward reaction, confirming that the VM1 reductase participates solely in VM1 inactivation in vivo.

  1. 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.

  2. [Cytogenetic investigations of bone marrow cells from mice exposed onboard biosatellite "Bion-M1"].

    Science.gov (United States)

    Dorozhkina, O V; Ivanov, A A

    2015-01-01

    The results of studying the mitotic activities and chromosomal aberrations in bone marrow cells from C57/BL6N mice with the help of the anaphase technique in 12 hours after completion of the 30-day "Bion-M1" mission and ground-based experiment using flight equipment are presented. A statistically reliable decline of the mitotic activity (0.74%) was found in cells taken from the space flown animals. In the ground-based experiment, a statistically reliable downward trend in proliferative activity (1.37%) was revealed after the comparison with groups of vivarium control (1.46-1.53%). In both experiments mice increased the number of initial mitotic phases (prophase + metaphase) relative to the sum of anaphases and telophases. The number of aberrant mitoses grew reliably in the group of flight animals by 29.7%, whereas in the ground-based experiment an upward trend was insignificant as their number increased up to 2.3% only. In the vivarium controls aberrant mitoses constituted 1.75-1.8%. An increase in chromosomal aberrations was largely due to such abnormalities as fragments. These findings seem to have been a result of summation of the effects of radiation and other stressful factors in space flight.

  3. THE M/M/1 QUEUE WITH WORKING VACATIONS AND VACATION INTERRUPTIONS

    Institute of Scientific and Technical Information of China (English)

    Jihong LI; Naishuo TIAN

    2007-01-01

    In this paper,we study the M/M/1 queue with working vacations and vacation interruptions.The working vacation is introduced recently,during which the server can still provide service on the original ongoing work at a lower rate.Meanwhile,we introduce a new policy:the server can come back from the vacation to the normal working level once some indices of the system,such as the number of customers,achieve a certain value in the vacation period.The server may come back from the vacation without completing the vacation.Such policy is called vacation interruption.We connect the above mentioned two policies and assume that if there are customers in the system after a service completion during the vacation period,the server will come back to the normal working level.In terms of the quasi birth and death process and matrix-geometric solution method,we obtain the distributions and the stochastic decomposition structures for the number of customers and the waiting time and provide some indices of systems.

  4. Glutathione s-transferase M1 and T1 genetic polymorphisms in Iranian patients with glaucoma

    Directory of Open Access Journals (Sweden)

    Fatemeh Kazemi Safa

    2014-05-01

    Full Text Available Objective(s:Glaucoma is the second leading cause of blindness and it is related to oxidative stress based on numerous studies. Glutathione S-transferases (GSTs are members of multigenic family, which have important role in cells as an antioxidant. In the present study, we examined the polymorphism of GSTT1 and GSTM1 deletion genotypes (T0M1, T1M0, and T0M0 in 100 Glaucoma patients (41with primary open angle glaucoma (PCAG, and 59 with primary closed angle glaucoma (POAG compared to 100 healthy subjects. Materials and Methods: GSTM1and GSTT1 polymorphisms were determined by multiplex polymerase chain reaction. Results: GSTM1 and GSTT1 null deletions genotypes were determined in 22 (53.7% and 7 (17.1% patients with PCAG and 34 (34% and 15 (15% in healthy subjects[VAIO1] . Comparison between patients and healthy subjects regarding GSTM1 and GSTT1 genotypes revealed increase of GSTM1 null deletions genotypes in patients with PCAG (P=0.03. Conclusion: It was concluded that the increased frequencies of GSTM1 null in patients with PCAG could be a risk factor for incidence of PCAG in the Iranian population.  

  5. Seasonal patterns of aflatoxin M1 contamination in commercial pasteurised milk from different areas in Thailand.

    Science.gov (United States)

    Suriyasathaporn, Witaya; Nakprasert, Watinee

    2012-01-01

    Aflatoxin M1 (AFM1) levels were determined in pasteurised milk from five commercial trademarks produced in different areas in Thailand. One hundred and twenty milk samples were collected from local markets in Chiang Mai province, Thailand, to evaluate AFM1 concentrations using immunoaffinity columns and high-performance liquid chromatography with fluorescence detection. The overall median AFM1 level was 0.023 µg L(-1) ranging from 0.004 to 0.293 µg L(-1). All trademarks had average AFM1 concentrations lower than 0.05 µg L(-1), with those in Trademarks 3 to 5 being higher than Trademarks 1 and 2 (P < 0.01). All trademarks had different seasonal patterns of AFM1, even though operating in the same area. However, only Trademark 3 showed significant differences of AFM1 levels between seasons. The results suggested that farm management factors, rather than environment factors, were likely to be the main cause of AFM1 contamination in dairy products.

  6. Rapid and specific gray matter changes in M1 induced by balance training.

    Science.gov (United States)

    Taubert, Marco; Mehnert, Jan; Pleger, Burkhard; Villringer, Arno

    2016-06-01

    Training-induced changes in cortical structure can be observed non-invasively with magnetic resonance imaging (MRI). While macroscopic changes were found mainly after weeks to several months of training in humans, imaging of motor cortical networks in animals revealed rapid microstructural alterations after a few hours of training. We used MRI to test the hypothesis of immediate and specific training-induced alterations in motor cortical gray matter in humans. We found localized increases in motor cortical thickness after 1h of practice in a complex balancing task. These changes were specific to motor cortical effector representations primarily responsible for balance control in our task (lower limb and trunk) and these effects could be confirmed in a replication study. Cortical thickness changes (i) linearly increased across the training session, (ii) occurred independent of alterations in resting cerebral blood flow and (iii) were not triggered by repetitive use of the lower limbs. Our findings show that motor learning triggers rapid and specific gray matter changes in M1.

  7. Occurrence of aflatoxin M1 in raw milk of five dairy species in Ahvaz, Iran.

    Science.gov (United States)

    Rahimi, E; Bonyadian, M; Rafei, M; Kazemeini, H R

    2010-01-01

    During November 2007 to December 2008, 311 samples of raw milk from cow, water buffalo, camel, sheep, and goat were collected in the Ahvaz (southwest Iran). All of the samples were analyzed for presence of aflatoxin M1 (AFM1) by competitive ELISA technique. AFM1 was found in 42.1% of the samples by average concentration of 43.3+/-43.8 ng/kg. The incidence rates of AFM1 in raw cow, water buffalo, camel, sheep, and goat milks were, 78.7%, 38.7%, 12.5%, 37.3%, and 27.1%, respectively. The concentration of AFM1 in all of the samples were lower than Iranian national standard and FDA limit (500 ng/l), but in 36% of raw cow milk, 8% water buffalo milk, 3.9% sheep milk, and 5.7% raw goat milk samples were higher than maximum tolerance limit accepted by European union/Codex Alimentarius Commission (50 ng/l). The results showed that the milk of camel, goat, and sheep is safe respect to AFM1 contamination in this area.

  8. Repeatability of ellipsometric data in cholera toxin G M1-ELISA structures

    Science.gov (United States)

    Castro, Leon G.; Thompson, Daniel W.; Tiwald, Thomas; Berberov, Emil M.; Woollam, John A.

    2007-04-01

    The need for repeated measurements in a wide range of biological testing due to statistical variations is well known. In this paper, we discuss a specific example in which the measurement probe is a spectroscopic ellipsometer. Repeatable results are needed in a wide range of applications such as drug testing, immunoassays and other tests for disease, and fundamental biomaterial research. The present paper seeks to help reduce the non-meaningful causes of lack of repeatability by identifying a large number of externally controllable factors. Another goal of this work was to quantify the effects of many of these factors on ellipsometric measurements. By exploiting the sensitivity of spectroscopic ellipsometry to ultrathin layers, improved ways to detect and quantitatively differentiate biological events can be explored. This initial work was motivated from an interest to distinguish one disease from another or discern effects of one drug from another using the high surface sensitivity of spectroscopic ellipsometry. In this paper, we investigate the example biological system of cholera toxin (CT) in an ELISA structure with monosialoganglioside (G M1).

  9. Binding of aflatoxin M1 to different protein fractions in ovine and caprine milk.

    Science.gov (United States)

    Barbiroli, A; Bonomi, F; Benedetti, S; Mannino, S; Monti, L; Cattaneo, T; Iametti, S

    2007-02-01

    The affinity of aflatoxin M1 toward the main milk protein fractions in ewe and goat milk was investigated by using an ELISA. This study took into account the possible effects of common dairy processes such as ultrafiltration, acidic or rennet curding, and production of ricotta from acidic or rennet whey. Treatments that allowed the separation of casein from whey proteins under conditions that do not alter the physical or chemical status of the proteins (such as ultracentrifugation) were used as a reference. None of the treatments used in typical dairy processes caused significant release of the toxin, in spite of the relevant changes they induced in the interactions among proteins. Only the combined heat and acidic treatment used for production of ricotta cheese altered the structure of whey proteins to the point where they lost their ability to bind the toxin. This study also showed that, regardless of the physical state of the sample, a commercial electronic nose device, in combination with appropriate statistical tools, was able to discriminate among different levels of sample contamination.

  10. Nonlinear phase of the compressional m=1 diocotron instability: Saturation and analogy with geophysical fluid dynamics

    Science.gov (United States)

    Delzanno, G. L.; Finn, J. M.; Lapenta, G.

    2002-12-01

    The nonlinear dynamics of a Penning trap plasma, including the effect of the finite length and end curvature of the plasma column, is studied. A new cylindrical particle-in-cell code, called KANDINSKY, has been implemented by using a new interpolation scheme. The principal idea is to calculate the volume of each cell from a particle volume, in the same manner as is done for the cell charge. With this new method, the density is conserved along streamlines and artificial sources of compressibility are avoided. The code has been validated with a number of tests. The code is then used to compare the dynamics of three different models: the standard Euler or drift-Poisson model, the modified drift-Poisson model [J. Finn et al. Phys. Plasmas 6, 3744 (1999); Phys. Rev. Lett. 84, 2401 (2000)] with compressional effects, and the quasigeostrophic model of geophysical fluid dynamics in the limit of the γ-plane approximation. The results of this investigation show that Penning traps can be used to simulate geophysical fluids. Moreover, the results for the m=1 diocotron instability reproduce qualitatively the experiments [C. F. Driscoll, Phy. Rev. Lett. 64, 645 (1990); C. F. Driscoll et al. Phys. Fluids B 2, 1359 (1990)]: The instability turns the plasma "inside-out" resulting at the end in a stable, monotonic profile.

  11. Loss of Forkhead box M1 promotes erythropoiesis through increased proliferation of erythroid progenitors.

    Science.gov (United States)

    Youn, Minyoung; Wang, Nan; LaVasseur, Corinne; Bibikova, Elena; Kam, Sharon; Glader, Bertil; Sakamoto, Kathleen M; Narla, Anupama

    2017-05-01

    Forkhead box M1 (FOXM1) belongs to the forkhead/winged-helix family of transcription factors and regulates a network of proliferation-associated genes. Its abnormal upregulation has been shown to be a key driver of cancer progression and an initiating factor in oncogenesis. FOXM1 is also highly expressed in stem/progenitor cells and inhibits their differentiation, suggesting that FOXM1 plays a role in the maintenance of multipotency. However, the exact molecular mechanisms by which FOXM1 regulates human stem/progenitor cells are still uncharacterized. To understand the role of FOXM1 in normal hematopoiesis, human cord blood CD34(+) cells were transduced with FOXM1 short hairpin ribonucleic acid (shRNA) lentivirus. Knockdown of FOXM1 resulted in a 2-fold increase in erythroid cells compared to myeloid cells. Additionally, knockdown of FOXM1 increased bromodeoxyuridine (BrdU) incorporation in erythroid cells, suggesting greater proliferation of erythroid progenitors. We also observed that the defective phosphorylation of FOXM1 by checkpoint kinase 2 (CHK2) or cyclin-dependent kinases 1/2 (CDK1/2) increased the erythroid population in a manner similar to knockdown of FOXM1. Finally, we found that an inhibitor of FOXM1, forkhead domain inhibitor-6 (FDI-6), increased red blood cell numbers through increased proliferation of erythroid precursors. Overall, our data suggest a novel function of FOXM1 in normal human hematopoiesis. Copyright© Ferrata Storti Foundation.

  12. Detection of aflatoxin M1 in human breast milk and raw cow's milk in Istanbul, Turkey.

    Science.gov (United States)

    Keskin, Yaşar; Başkaya, Ruhtan; Karsli, Seher; Yurdun, Türkan; Ozyaral, Oğuz

    2009-04-01

    This survey was undertaken to determine the extent of aflatoxin M1 (AFM1) contamination in human breast milk and raw cow's milk in Istanbul, Turkey. Samples of human and raw cow's milk were collected randomly and analyzed for AFM1 using an enzyme-linked immunosorbent assay and high-performance liquid chromatography with fluorescence detection in which the samples were cleaned up with immunoaffinity columns. In this study, AFM, was detected in 8 (13.1%) of 61 human breast milk samples examined (mean +/- SD level, 5.68 +/- 0.62 ng/liter; range, 5.10 to 6.90 ng/liter) and 20 (33.3%) of 60 raw cow's milk samples examined (range, 5.40 to 300.20 ng/liter). Five (8.3%) of the positive raw cow's milk samples had AFM1 levels (153.52 +/- 100.60 ng/liter; range, 61.20 to 300.20 ng/liter) that were higher than the maximum tolerance limit (0.05 ppb) stipulated by regulations in Turkey and some other countries.

  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. First observation of the M1 transition $\\psi^\\prime\\to \\gamma\\eta_c^\\prime$

    CERN Document Server

    Ablikim, M; 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 million $\\psi^\\prime$ 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: $\\psi^\\prime\\to\\gamma\\eta_c^\\prime$. Analyses of the processes $\\psi^\\prime\\to \\gamma\\eta_c^\\prime$ with $\\eta_c^\\prime\\to \\K_S^0 K\\pi$ and $K^+K^-\\pi^0$ gave an $\\eta_c^\\prime$ signal with a statistical significance of greater than 10 standard deviations under a wide range of assumptions about the signal and background properties. The data are used to obtain measurements of the $\\eta_c^\\prime$ mass ($M(\\eta_c^\\prime)=3637.6\\pm 2.9_\\mathrm{stat}\\pm 1.6_\\mathrm{sys}$ MeV/$c^2$), width ($\\Gamma(\\eta_c^\\prime)=16.9\\pm 6.4_\\mathrm{stat}\\pm 4.8_\\mathrm{sys}$ MeV), and the product branching fraction ($\\BR(\\psi^\\prime\\to \\gamma\\eta_c^\\prime)\\times \\BR(\\eta_c^\\prime\\to K\\bar K\\pi) = (1.30\\pm 0.20_\\mathrm{stat}\\pm 0.30_\\mathrm{sys})\\tim...

  15. The aflatoxin M1 crisis in the Serbian dairy sector: the year after.

    Science.gov (United States)

    Miocinovic, Jelena; Keskic, Tanja; Miloradovic, Zorana; Kos, Andrea; Tomasevic, Igor; Pudja, Predrag

    2017-03-01

    During the last 3 years, high aflatoxin M1 (AFM1) concentrations in milk and dairy products occurred in Serbia. It resulted in periodical change of the official regulations regarding maximum levels (MLs) of AFM1 as set by the Serbian Government. The aim of this study was to compare the occurrence of AFM1 in raw milk and dairy products during 2015 and also to determine whether there were some differences in AFM1 level among seasons. The AFM1 level exceeded the European Union ML in 29.3% of raw milk and 4.2% of milk product samples. The highest level of AFM1 in raw milk was found during the autumn season, while during the rest of the 2015, it was significantly lower. Although the improvement of dairy products safety was evident in 2015 when compared to 2013 and 2014, the cause of high concentrations in raw milk remained unresolved yet. This study indicates that dairy plants introduced control measures and refused reception of too high contaminated raw milk.

  16. Assessment of aflatoxin M1 in maternal breast milk in Eastern Turkey.

    Science.gov (United States)

    Atasever, Meryem; Yildirim, Yeliz; Atasever, Mustafa; Tastekin, Ayhan

    2014-04-01

    Breastfeeding may be considered as a risk factor for aflatoxin M1 (AFM1) exposure in early infancy. Hence, AFM1 levels in maternal breast milk (MBM) and the correlation between moldy cheese consumption of lactating mothers and infant exposure to AFM1 were investigated in this study. MBM samples from 73 lactating women randomly selected in hospitals located in Eastern Turkey were analysed for the presence of AFM1 using competitive ELISA. Out of 73 lactating mothers, 44 of them had the habit of cheese consumption (at least once a week), while remaining 29 had no such habit. AFM1 was detected in MBM of 18 out of 73 samples (24.6%); 12 MBM of 44 lactating mothers with moldy cheese consumption habit (27.2%) and 6 MBM of 29 mothers with no such habit (20.6%) with the range of 1.3-6.0 ng/l. None of the samples exceeded the limit set by EU and Turkish legislations. Moldy cheese consumption habit of lactating mothers exhibited no significant correlation with the presence of AFM1 in their milk (p>0.05). The results indicated that the relative risk of infant AFM1 exposure via MBM of moldy cheese consuming mother was not higher than MBM of mothers with no such habit.

  17. 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.

  18. Structural damage and functional reorganization in ipsilesional m1 in well-recovered patients with subcortical stroke.

    Science.gov (United States)

    Zhang, Jing; Meng, Liangliang; Qin, Wen; Liu, Ningning; Shi, Fu-Dong; Yu, Chunshui

    2014-03-01

    Both structural atrophy and functional reorganization of the primary motor cortex (M1) have been reported in patients with subcortical infarctions affecting the motor pathway. However, the relationship between structural impairment and functional reorganization in M1 remains unclear. Twenty-six patients exhibiting significant recovery after subcortical infarctions were investigated using multimodal MRI techniques. Structural impairment was assessed via cortical thickness, and functional reorganization was analyzed using task-evoked activation, amplitude of low-frequency fluctuation, and resting-state functional connectivity. Compared with healthy controls, patients with stroke exhibited reduced cortical thickness in the ipsilesional M1; however, this region exhibited increased task-evoked activation, amplitude of low-frequency fluctuation, and resting-state functional connectivity in these patients. Patients with stroke demonstrated increased task-evoked activation in another ipsilesional M1 region, in which increased amplitude of low-frequency fluctuation and resting-state functional connectivity were observed. The structural and functional changes in M1 were located selectively in the ipsilesional hemisphere. We provide convincing evidence that indicates extensive functional reorganization in the ipsilesional M1 of patients with chronic subcortical infarctions, including the structurally impaired M1 region.

  19. 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.

  20. Inhibition of M1 macrophage activation in adipose tissue by berberine improves insulin resistance.

    Science.gov (United States)

    Ye, Lifang; Liang, Shu; Guo, Chao; Yu, Xizhong; Zhao, Juan; Zhang, Hao; Shang, Wenbin

    2016-12-01

    Insulin resistance is associated with a chronic inflammation in adipose tissue which is propagated by a phenotypic switch in adipose tissue macrophage (ATM) polarization. This study aimed to investigate whether berberine, the major alkaloid of rhizoma coptidis, can improve insulin resistance through inhibiting ATM activation and inflammatory response in adipose tissue. High-fat-diet induced obese mice were administered oral with berberine (50mg/kg/day) for 14days. ATMs were analysed using FACS and insulin resistance was evaluated. Expressions of pro-inflammatory cytokines and activation of inflammatory pathways were detected. The chemotaxis of macrophages was measured. Glucose consumption and insulin signalling of adipocytes were examined. Berberine significantly decreased F4/80(+)/CD11c(+)/CD206(-) cells in the stromal vascular fraction from adipose tissue and improved glucose tolerance in obsess mice. In addition, berberine reduced the elevated levels of serum TNF-α, IL-6 and MCP-1 and the expressions of TNF-α, IL-6 and MCP-1 and attenuated the phosphorylation of JNK and IKKβ and the expression of NF-κB p65 in the obese adipose tissue, Raw264.7 macrophages and 3T3-L1 adipocytes, respectively. The phosphorylation of IRS-1 (Ser307) was inhibited by berberine in adipose tissue and cultured adipocytes. The phosphorylation of AKT (Ser473) was increased in berberine-treated adipose tissue. Conditioned medium from adipocytes treated with berberine reduced the number of infiltrated macrophages. Berberine partly restored the impaired glucose consumption and the activation of IRS-1 (Ser307) in adipocytes induced by the activation of macrophages. Our findings imply that berberine improves insulin resistance by inhibiting M1 macrophage activation in adipose tissue. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Transport of Aflatoxin M1 in human intestinal Caco-2/TC7 cells

    Directory of Open Access Journals (Sweden)

    Francesca eCaloni

    2012-06-01

    Full Text Available Aflatoxin M1 (AFM1 is a hydroxylated metabolite of aflatoxin B1 (AFB1. After it is formed, it is secreted in the milk of mammals.Despite the potential risk of human exposure to AFM1, data reported in literature on the metabolism, toxicity and bioavailability of this molecule are limited and out of date. The aim of the present research was to study the absorption profile of AFM1 and possible damage to tight junctions of the intestinal Caco-2/TC7 clone grown on microporous filter supports. These inserts allowed for the separation of the apical and basolateral compartments which correspond to the in vivo lumen and the interstitial space/vascular systems of intestinal mucosa respectively.In this study, the Caco-2/TC7 cells were treated with different AFM1 concentrations (10-10,000 ng/kg for short (40 minutes and long periods of time (48 hours. The AFM1 influx/efflux transport and effects on tight junctions were evaluated by measuring trans-epithelial electrical resistance and observing tight junction protein (Zonula occludens-1 and occludin localization.The results showed that: i when introduced to the apical and basolateral compartments, AFM1 was poorly absorbed by the Caco-2/TC7 cells but its transport across the cell monolayer occurred very quickly (Papp value of 105.10 ± 7.98 cm/s x 10-6. ii The integrity of tight junctions was not permanently compromised after exposure to the mycotoxin. Viability impairment or barrier damage did not occur either.The present results contribute to the evaluation of human risk exposure to AFM1, although the AFM1 transport mechanism need to be clarified.

  2. The Hotspot for (Global) One Health in Primary Food Production: Aflatoxin M1 in Dairy Products.

    Science.gov (United States)

    Frazzoli, Chiara; Gherardi, Paola; Saxena, Navneet; Belluzzi, Giancarlo; Mantovani, Alberto

    2016-01-01

    One Health involves the multifaceted environment-animal-human web: nevertheless, the role of toxicological issues has yet to be fully explored in this context. Aflatoxin B1 (AFB1) contamination of feeds is a risk for the health of several farm animals, including fishes; milk is the only food of animal origin where a significant feed-food carry over may occur. The main AFB1-related compound present in milk is the hydroxy-metabolite aflatoxin M1 (AFM1). Besides contamination of raw milk, AFM1 is of concern for the whole dairy chain; AFM1 may also contaminate the milk of several other ruminants used for milk/dairy production. In a One Health perspective, milk represents a sentinel matrix for AFB1 vulnerability of the agro-food system, that is crucial in a phase when food/nutritional security becomes a global issue and climatic changes may affect agricultural productions. In the global setting, food chain exposure to long-term toxicants, such as AFM1, is a growing concern for economically developing countries, whereas global trade and climatic change makes AFM1 an emerging hot issue in economically developed countries as well. We critically review the state of the art on AFM1 risk assessment and risk management using two scenarios as case studies: a European Union country where the health system aims at ensuring a high-level protection of food chain (Italy) and the world's largest (and economically developing) producer of dairy products by volume (India). The case studies are used to provide building blocks for a global One Health framework.

  3. NST and IRIS multi-wavelength observations of an M1.0 class solar flare

    Science.gov (United States)

    Vargas Domínguez, Santiago; Sadykov, Viacheslav; Kosovichev, Alexander; Sharykin, Ivan; Struminsky, Alexei; Zimovets, Ivan

    2015-08-01

    Although solar flares are the most energetic events in the Solar System and have direct impact in the interplanetary space and ultimately in our planet, there are still many unresolved issues concerning their generation, the underlying processes of particle acceleration involved, the effect at different layer in the solar atmosphere, among others. This work presents new coordinated observations from the New Solar Telescope (NST) and the space telescope IRIS that acquired simultaneous observations of an M1.0 class flare occurred on 12 June, 2014 in active region NOAA 12087. NST filtergrams using the TiO filter, together with chromospheric data from the Halpha line allow us to study the evolution of the event from the first signs of the intensification of the intensity in the region. We focused on a small portion where the intensity enhancement in Halpha (blue and red wings) seems to be triggered, and discovered a rapid expansion of a flux-rope structure near the magnetic neutral line, in the sequence of high-resolution photospheric images. IRIS observations evidenced strong emission of the chromospheric and transition region lines during the flare. Jet-like structures are detected before the initiation of the flare in chromospheric lines and strong non-thermal emission in the transition region at the beginning of the impulsive phase. Evaporation flows with velocities up to 50 km/s occurred in the hot chromospheric plasma. We interpreted the result in terms of the “gentle” evaporation that occurs after accelerated particles heat the chromosphere.

  4. Aflatoxin M1 contamination of human breast milk in Isfahan, Iran

    Science.gov (United States)

    Jafarian-Dehkordi, Abbas; Pourradi, Nasibeh

    2013-01-01

    Background: During the last decades there has been great attention paid to aflatoxins. They are highly toxic, immunosuppressive, mutagenic, teratogenic, and carcinogenic compounds. Aflatoxin M1 (AFM1), a hydroxylated metabolite of aflatoxin B1 (AFB1), is formed in the liver and excreted into the breast milk. It is considered to cause certain hygienic risks for infant health. The aim of this study was to evaluate the presence of the AFM1 in the breast milk using AFM1 in milk as a biomarker for exposure to aflatoxin B1 and determine the level of AFM1 contamination in the lactating mothers in Isfahan, Iran. Materials and Methods: This study was carried out on 80 lactating women randomly selected from two urban health centers. Mother's milk samples and information on food intake were collected from the participants using structured food-frequency questionnaire. Breast milk samples were tested for AFM1 by a competitive ELISA technique. Results: Our findings showed that only one sample was contaminated with AFM1 with concentrations of 6.8 ng/L. However, the AFM1 level in this sample was lower than the maximum tolerable limit (25 ng/L) accepted by the European Communities and Codex Alimentarius. Conclusion: Although the concentration of AFM1 in none of the samples was higher than the acceptable level, the presence of AFM1 in only one of them confirms the need for developing strategies to reduce exposure to aflatoxin in foods and to carry out biological monitoring of aflatoxins as a food quality control measure routinely. PMID:24524032

  5. Glutathione S-transferase M1 null genotype related to poor prognosis of colorectal cancer.

    Science.gov (United States)

    Yan, Shushan; Wang, Zengfang; Wang, Zengyan; Duan, Quanhong; Wang, Xiaochen; Li, Jun; Sun, Beicheng

    2016-08-01

    Published studies showed controversial findings about the relationship between glutathione S-transferase M1 (GSTM1) null genotype and clinical outcomes of patients with colorectal cancer. We performed a meta-analysis to quantitatively assess the association between GSTM1 null genotype and prognosis of patients with colorectal cancer. We systematically searched Pubmed, Embase, and Web of Science to identify prospective or retrospective cohort studies assessing the association of GSTM1 null genotype with overall survival (OS) or disease-free survival (DFS) in colorectal cancer. The hazard ratios (HRs) and 95 % confidence intervals (95 % CIs) were used to assess the association of GSTM1 null genotype with OS or DFS. Finally, 15 studies from 14 publications with 4326 colorectal cancer patients were included into the meta-analysis. There was no heterogeneity in the meta-analysis relating OS (I (2) = 0 %) and DFS (I (2) = 0 %). Overall, GSTM1 null genotype was significantly associated with poor OS in patients with colorectal cancer (HR = 1.18, 95 % CI 1.07-1.30, P = 0.001). In addition, GSTM1 null genotype was also significantly associated with poor DFS in patients with colorectal cancer (HR = 1.15, 95 % CI 1.03-1.28, P = 0.015). No obvious risk of publication bias was observed. GSTM1 null genotype is significantly associated with poor OS and DFS in patients with colorectal cancer, which suggests that GSTM1 null genotype confers poor effect on the prognosis of colorectal cancer.

  6. Deletion of Forkhead Box M1 transcription factor from respiratory epithelial cells inhibits pulmonary tumorigenesis.

    Directory of Open Access Journals (Sweden)

    I-Ching Wang

    Full Text Available The Forkhead Box m1 (Foxm1 protein is induced in a majority of human non-small cell lung cancers and its expression is associated with poor prognosis. However, specific requirements for the Foxm1 in each cell type of the cancer lesion remain unknown. The present study provides the first genetic evidence that the Foxm1 expression in respiratory epithelial cells is essential for lung tumorigenesis. Using transgenic mice, we demonstrated that conditional deletion of Foxm1 from lung epithelial cells (epFoxm1(-/- mice prior to tumor initiation caused a striking reduction in the number and size of lung tumors, induced by either urethane or 3-methylcholanthrene (MCA/butylated hydroxytoluene (BHT. Decreased lung tumorigenesis in epFoxm1(-/- mice was associated with diminished proliferation of tumor cells and reduced expression of Topoisomerase-2alpha (TOPO-2alpha, a critical regulator of tumor cell proliferation. Depletion of Foxm1 mRNA in cultured lung adenocarcinoma cells significantly decreased TOPO-2alpha mRNA and protein levels. Moreover, Foxm1 directly bound to and induced transcription of the mouse TOPO-2alpha promoter region, indicating that TOPO-2alpha is a direct target of Foxm1 in lung tumor cells. Finally, we demonstrated that a conditional deletion of Foxm1 in pre-existing lung tumors dramatically reduced tumor growth in the lung. Expression of Foxm1 in respiratory epithelial cells is critical for lung cancer formation and TOPO-2alpha expression in vivo, suggesting that Foxm1 is a promising target for anti-tumor therapy.

  7. 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.

  8. Aflatoxin B1 and M1 Degradation by Lac2 from Pleurotus pulmonarius and Redox Mediators

    Science.gov (United States)

    Loi, Martina; Fanelli, Francesca; Zucca, Paolo; Liuzzi, Vania C.; Quintieri, Laura; Cimmarusti, Maria T.; Monaci, Linda; Haidukowski, Miriam; Logrieco, Antonio F.; Sanjust, Enrico; Mulè, Giuseppina

    2016-01-01

    Laccases (LCs) are multicopper oxidases that find application as versatile biocatalysts for the green bioremediation of environmental pollutants and xenobiotics. In this study we elucidate the degrading activity of Lac2 pure enzyme form Pleurotus pulmonarius towards aflatoxin B1 (AFB1) and M1 (AFM1). LC enzyme was purified using three chromatographic steps and identified as Lac2 through zymogram and LC-MS/MS. The degradation assays were performed in vitro at 25 °C for 72 h in buffer solution. AFB1 degradation by Lac2 direct oxidation was 23%. Toxin degradation was also investigated in the presence of three redox mediators, (2,2′-azino-bis-[3-ethylbenzothiazoline-6-sulfonic acid]) (ABTS) and two naturally-occurring phenols, acetosyringone (AS) and syringaldehyde (SA). The direct effect of the enzyme and the mediated action of Lac2 with redox mediators univocally proved the correlation between Lac2 activity and aflatoxins degradation. The degradation of AFB1 was enhanced by the addition of all mediators at 10 mM, with AS being the most effective (90% of degradation). AFM1 was completely degraded by Lac2 with all mediators at 10 mM. The novelty of this study relies on the identification of a pure enzyme as capable of degrading AFB1 and, for the first time, AFM1, and on the evidence that the mechanism of an effective degradation occurs via the mediation of natural phenolic compounds. These results opened new perspective for Lac2 application in the food and feed supply chains as a biotransforming agent of AFB1 and AFM1. PMID:27563923

  9. 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 Birk

    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...... 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....

  10. Evolutionary Trajectories of Beta-Lactamase CTX-M-1 Cluster Enzymes: Predicting Antibiotic Resistance

    Science.gov (United States)

    Novais, Ângela; Comas, Iñaki; Baquero, Fernando; Cantón, Rafael; Coque, Teresa M.; Moya, Andrés; González-Candelas, Fernando; Galán, Juan-Carlos

    2010-01-01

    Extended-spectrum beta-lactamases (ESBL) constitute a key antibiotic-resistance mechanism affecting Gram-negative bacteria, and also an excellent model for studying evolution in real time. A shift in the epidemiology of ESBLs is being observed, which is characterized by the explosive diversification and increase in frequency of the CTX-M-type β-lactamases in different settings. This provides a unique opportunity for studying a protein evolutionary radiation by the sequential acquisition of specific mutations enhancing protein efficiency and fitness concomitantly. The existence of driver antibiotic molecules favoring protein divergence has been investigated by combining evolutionary analyses and experimental site-specific mutagenesis. Phylogenetic reconstruction with all the CTX-M variants described so far provided a hypothetical evolutionary scenario showing at least three diversification events. CTX-M-3 was likely the enzyme at the origin of the diversification in the CTX-M-1 cluster, which was coincident with positive selection acting on several amino acid positions. Sixty-three CTX-M-3 derivatives containing all combinations of mutations under positively selected positions were constructed, and their phenotypic efficiency was evaluated. The CTX-M-3 diversification process can only be explained in a complex selective landscape with at least two antibiotics (cefotaxime and ceftazidime), indicating the need to invoke mixtures of selective drivers in order to understand the final evolutionary outcome. Under this hypothesis, we found congruent results between the in silico and in vitro analyses of evolutionary trajectories. Three pathways driving the diversification of CTX-M-3 towards the most complex and efficient variants were identified. Whereas the P167S pathway has limited possibilities of further diversification, the D240G route shows a robust diversification network. In the third route, drift may have played a role in the early stages of CTX-M-3 evolution

  11. 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

  12. Tracklines of Multichannel Seismics Survey Collected During USGS Cruise M1-98-GM (GOM98LINE.SHP)

    Data.gov (United States)

    U.S. Geological Survey, Department of the Interior — Shapefile showing tracklines of Multichannel Seismics Survey Collected During USGS Cruise M1-98-GM. This cruise was to the Mississippi Canyon region of the Gulf of...

  13. Regio-selectively reduced streptogramin A analogue, 5,6-dihydrovirginiamycin M1 exhibits improved potency against MRSA.

    Science.gov (United States)

    Hoang, N H; Huong, N L; Shrestha, A; Sohng, J K; Yoon, Y J; Park, J W

    2013-11-01

    A newly reduced macrocyclic lactone antibiotic streptogramin A, 5,6-dihydrovirginiamycin M1 was created by feeding virginiamycin M1 into a culture of recombinant Streptomyces venezuelae. Its chemical structure was spectroscopically elucidated, and this streptogramin A analogue showed twofold higher antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA) compared with its parent molecule virginiamycin M1. Docking studies using the model of streptogramin A acetyltransferase (VatA) suggested that the newly generated analogue binds tighter with overall lower free energy compared with the parent molecule virginiamycin M1. This hypothesis was validated experimentally through the improvement of efficacy of the new analogue against MRSA strains. The biotransformation approach presented herein could have a broad application in the production of reduced macrocyclic molecules.

  14. Complete genome sequence of Streptococcus pyogenes M1 476, isolated from a patient with streptococcal toxic shock syndrome.

    Science.gov (United States)

    Miyoshi-Akiyama, Tohru; Watanabe, Shinya; Kirikae, Teruo

    2012-10-01

    Here, we report the completely annotated genome sequence of Streptococcus pyogenes M1 476 isolated from a patient with streptococcal toxic shock syndrome (STSS) during pregnancy. The genome sequence will provide new insights into the mechanisms underlying STSS.

  15. Complete Genome Sequence of Streptococcus pyogenes M1 476, Isolated from a Patient with Streptococcal Toxic Shock Syndrome

    OpenAIRE

    Miyoshi-Akiyama, Tohru; WATANABE, Shinya; Kirikae, Teruo

    2012-01-01

    Here, we report the completely annotated genome sequence of Streptococcus pyogenes M1 476 isolated from a patient with streptococcal toxic shock syndrome (STSS) during pregnancy. The genome sequence will provide new insights into the mechanisms underlying STSS.

  16. Aflatoxin M1 in samples of "minas" cheese commercialized in the city of Belo Horizonte - Minas Gerais/Brazil Aflotoxina M1 em amostras de queijo "minas" comercializada na cidade de Belo Horizonte - Minas Gerais/ Brasil

    Directory of Open Access Journals (Sweden)

    Guilherme PRADO

    2000-12-01

    Full Text Available Milk products such as cheeses may be contaminated by aflatoxin M1 when dairy cattle have consumed feeds contaminated with aflatoxin B1. Samples of "Minas" cheeses (fresh, canastra and standard were collected by the Inspection Service in the Mercado Central in Belo Horizonte city, Minas Gerais - Brazil. A purified extract was obtained by extraction with dichloromethane followed by a washing with n-hexane and immunoaffinity column purification. The quantification of aflatoxin M1 was done by high performance liquid chromatography (HPLC using a fluorescence detector. Recoveries were about 75%. In 56 of the 75 samples (74.7%, the presence of aflatoxin M1 was detected in concentrations ranging between 0.02 and 6.92ng/g of cheese. In the positive cases ( > or = 0.02ng/g the mean contamination level of aflatoxin M1 was 0.08ng/g in fresh cheese, 0.36ng/g in canastra cheese and 0.62ng/g in standard cheese. No aflatoxin M1 maximum tolerance level in cheese has been established in Brazil.Produtos derivados de leite, como queijo, podem estar contaminados com aflatoxina M1 quando o gado leiteiro consome ração contaminada com aflatoxina B1. Amostras de queijo "Minas" ( frescal, canastra e padrão foram coletados pela Vigilância Sanitária de Minas Gerais - Brasil. Foi obtido um extrato purificado através de extração com diclorometano, seguido de lavagem com n-hexano e purificação em coluna de imunoafinidade. A quantificação da aflatoxina M1 foi feita por cromatografia líquida de alta eficiência (CLAE usando detetor de fluorescência. Os valores de recuperação foram em torno de 75%. A presença de aflatoxina M1 foi detectada em 56 das 75 amostras (74,7% e a faixa de concentração observada foi 0,02 a 6,92ng/g de queijo. Dentre os valores positivos ( > ou = 0,02ng/g a média de contaminação de aflatoxina M1 foi 0,08ng/g para queijo frescal, 0,36ng/g para queijo canastra e 0,62ng/g para queijo padrão. O Brasil não apresenta nível de toler

  17. FoxM1和ADAM17在乳腺癌中的表达及其临床意义%Expression and clinical significance of FoxM1 and ADAM17 in breast cancer

    Institute of Scientific and Technical Information of China (English)

    张艳; 乔炜超; 孙影; 张雪鹏

    2016-01-01

    目的:探讨叉头框蛋白M1(FoxM1)与ADAM17在乳腺癌中的表达、相关性及临床意义。方法采用免疫组织化学法检测2014年6月~2015年12月华北理工大学附属医院浸润性乳腺癌(乳腺癌组)62例、乳腺纤维腺瘤(乳腺纤维腺瘤组)33例和正常乳腺组织(对照组)31例中FoxM1和ADAM17的表达,分析两者之间的关系以及其与乳腺癌临床病理特征的相关性。结果 FoxM1和ADAM17在对照组、乳腺纤维腺瘤组、乳腺癌组中的染色指数分别为0.49±0.11、2.13±0.25、9.58±0.95和0.56±0.17、1.87±0.22、9.40±1.17。乳腺癌组FoxM1和ADAM17表达显著高于乳腺纤维腺瘤组,乳腺纤维腺瘤组FoxM1、ADAM17表达高于对照组,差异均有统计学意义(P0.05)。FoxM1和ADAM17在乳腺癌中的表达呈正相关(r=0.68,P0.05) , but it was associated with the metastasis of axillary lymph nodes (P< 0.05). Correlation analysis showed that the expression of FoxM1 and ADAM17 in breast cancer was positively correlated (r=0.68, P<0.05). Conclusion There is high level of FoxM1 and ADAM17 in inva-sive carcinoma, and a positive correlation between them. Positive expression of FoxM1 and ADAM17 is positive associ-ation with axillary lymph node metastasis, but not with age and tumor size in patients with invasive carcinoma of the breast.

  18. 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....

  19. Excitation of internal m = 1 mode during application of resonant magnetic perturbations on J-TEXT tokamak

    Science.gov (United States)

    Li, Jianchao; Hu, Qiming; Ding, Yonghua; Zhang, Xiaoqing; Yu, Qingquan; Yang, Zhoujun; Chen, Zhipeng; Li, Da; Rao, Bo; Wang, Nengchao; Zhuang, Ge; the J-TEXT Team

    2017-08-01

    The excitation of internal m = 1 mode during application of resonant magnetic perturbations (RMPs) is observed on J-TEXT tokamak. It is found that the sawtooth oscillation disappears after RMPs penetration, and subsequently an internal m = 1 mode with a frequency around 2 kHz appears, were m and n are the poloidal and toroidal mode numbers, respectively. In addition, the internal m = 1 mode often coexists with a rotating m/n = 2/1 tearing mode, and its frequency increases by about 0.5 kHz when the 2/1 tearing mode is locked by RMPs. The bispectrum analysis proves that the m = 1 mode interacts with the rotating 2/1 tearing mode, which implies the mode coupling between these two modes. The frequency of m = 1 mode increases for higher electron density. These results reveal that, the internal m = 1 mode can be excited by RMPs and coexist with both locked and rotating 2/1 mode due to toroidal mode coupling.

  20. Bivariate flow cytometric analysis of DNA content versus immunopositivity for ribonucleotide reductase M1 subunit in the cell cycle.

    Science.gov (United States)

    Mangiarotti, R; Bottone, M G; Danova, M; Pellicciari, C

    1998-06-01

    Ribonucleotide reductase (RR) is a cytoplasmatic enzyme catalyzing the reduction of all four ribonucleotides to their corresponding deoxyribonucleotides. Its activity strongly correlates to the rate of DNA synthesis. By using a specific monoclonal antibody against the large M1 subunit of RR, we assessed the expression of M1-RR versus DNA content by dual-parameter flow cytometry. The aim of this paper was to compare the variations in the immunopositivity for M1-RR during the cell cycle to the positivity for other cell cycle markers identifying either proliferating cells (Ki-67 and PCNA) or quiescent cells (statin). To do this, normal human embryonic fibroblasts in different growth conditions as well as several other mammalian cell lines (rat C6 glioma cells; mouse 3T3 fibroblasts and B16 melanoma cells; human epithelial EUE cells and mammary carcinoma MCF-7 cells) were used. The expression of M1-RR antigen was found to correlate positively with the expression of Ki-67 and PCNA, and negatively with the expression of statin. During early G1 phase, M1-RR becomes detectable by specific antibodies relatively later compared to PCNA and Ki-67; therefore, the lack of immunopositivity for M1-RR cannot be taken as an absolute indication of cell quiescence in G0.

  1. 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.

  2. The fork head box M1 effects on human colon cancer cells malignant phenotype%叉头框转录因子 M1对人结肠癌细胞恶性表型的影响

    Institute of Scientific and Technical Information of China (English)

    冒晓蓓; 陈龙邦; 刘小北; 徐凯; 褚晓源; 郁红菊; 薛利军; 陈亚楠; 任丽丽; 戴婷婷

    2014-01-01

    Objective The invasion and metastasis of colon cancer often leads to treatment failure and mortality in patients . Our research is to investigate the influence of FoxM 1 to malignant human colon cancer line . Methods In two human colon cancer lines, the protein and mRNA expression levels of FoxM 1 were analyzed with the application of RT-PCR and Western blot , from which high-expressed HT-29 and low-expressed HCT-116 were determined.The expression of FoxM1 was down-regulated by RNA interfering in HT-29 and up-regulated by constructing overexpression transgenic line in HCT-116.The proliferation of the above cells was assayed by healing method;while the metastasis and invasion ability were examined by Transwell chamber assay . Results Two colon cancer lines were selected with high-expression or low-expression of FoxM1 separately named HT-29 and HCT-116.Application of PEX-2-FoxM1 raised after HCT-116 cells express FoxM1, cell scratches in HCT-116 experimetal group ([70.92 ±1.48]%) compared with HCT-116 control group([16.92 ±4.05]%)and HCT-116 blank control group([16.66 ±2.63]%) will markedly enhance its capabil-ity of healing (P<0.05), Transwell Chambers in membrane cells in HCT-116 experimetal group (186.0 ±6.8) compared with HCT-116 control group(42.0 ±2.0) and HCT-116 blank control grou (37.0 ± 2.2)was increased (P<0.05).On the other hand, the applied pG-PH-shFoxM1 can reduce FoxM1 expression in HT-29 cell, cell scrat-ches healing ability in HT-29 experimetal group ( [ 10 .37 ± 3.86]%) compared with HT-29 control group([34.63 ±2.35]%)and HT-29 blank control group([67.36 ±2.61]%) decreased significantly (P<0.05), Transwell Chambers in membrane cells in HT-29 experimetal group (53.0 ±1.8)compared with HT-29 control group(95.0 ±2.2)and HT-29 blank control grou(118.0 ±4.0) was also reduced (P<0.05). Conclusion The expression of FoxM1 is in close relation to the invasion and metastasis of CRC .The fact that the siRNA interfering FoxM1 could effectively

  3. 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

    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 (S1P1–5) 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 S1P1. In contrast, M1-polarized macrophages significantly downregulated S1P4. 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.

  4. Determination of aspergillus flavus toxin M1 in milk by resonance light scattering%共振光散射法检测牛奶中黄曲霉毒素M1

    Institute of Scientific and Technical Information of China (English)

    黄明元; 刘倩楠; 李兰芳

    2013-01-01

    目的:建立一种基于大分子物质环糊精的共振散射光色谱差异测定牛奶中残余黄曲霉毒素M1的新型检测方法.方法:β-环糊精与黄曲霉毒素M1结合后,不同浓度黄曲霉毒素M1与环糊精形成的包合物存在不同强度的共振散射光光谱,用共振瑞利散射光对黄曲霉毒素M1进行检测.结果:在波长为335 nm处共振光散射增强强度与黄曲霉毒素M1的浓度呈线性关系.在pH =4.0~5.0时,包合物形成的最佳温度为60℃,静置时间为1h,方法的检出限为0.38 ng/ml;线性范围为0ng/nd~8.0 ng/ml,线性相关系数r=0.992回收率为85%~ 108%.结论:本方法可简便,快速地测定牛奶中的黄曲霉毒素M1,结果可靠.%objective:A new method for determination of residual aspergillus flavus toxin M1 in milk was established based on macromolecular material cyclodextrin and resonance light scattering spectrum difference.Methods:After combination of beta cyclodextrin and aspergillus flavus toxin M1,clathrate formed by different concentrations of aspergillus flavus toxin M1 and cyclodextrin showed resonance scattering light spectrum had various intensity,then resonance rayleigh scattering light was used to detect aspergillus flavus toxin M1.Results:At the wavelength of 335 nm,the intensity of resonance light scattering was linear with concentration of aspergillus flavus toxin M1.When the pH value was 4.0 ~ 5.0,the optimum temperature of inclusion formation was 60 ℃ and the standing time was 1 h.The detection limit of the method was 0.38 ng/ml,the linear range was 0 ng/ml ~ 8.0 ng/ml with correlation coefficient of r =0.992 and recovery of 85 % ~ 108%.Conclusion:The method is simple and fast in determining aspergillus flavus toxin M1 in milk,with reliable results.

  5. 替米沙坦对小鼠巨噬细胞 M1/M2亚型极化的影响%Effect of Telmisartan on mice macrophage M1/M2 polarization

    Institute of Scientific and Technical Information of China (English)

    邢亦明; 胡泽平; 王邦宁; 周青; 汪渊

    2016-01-01

    Objective To investigate the effect of Telmisartan on the M1 /M2 polarization of mice macrophage . Methods Mice macrophage was induced to M1 /M2 polarization by LPS +IFN-γand IL-4 respectively, and tested by immunofluorescence.Meanwhile cells were treated with 0.1,1,10 μmol /L Telmisartan,blank control group and vehicle control group were established at the same time .The biomarkers iNOS and Arg Ⅰ were tested by Western blot, and the cytokines IL-6 and IL-10 were tested by ELISA assay.Results The biomarker iNOS and IL-6,secre-ted by M1 macrophage, were apparently increased in the macrophages induced by LPS +IFN-γ.However, after be-ing treated with Telmisartan,the expressions of iNOS and IL-6 were obviously decreased(P <0.05), as the concen-tration higher the expression lower .While, the expression of Arg I and IL-10, which represented the M2 macro-phage, increased ( P <0.05).Conclusion Telmisartan can inhibit the M1 polarization of mice macrophage RAW264.7 induced by LPS and IFN-γand transform M1 macrophage polarization to M2 macrophage polarization.%目的探讨替米沙坦对小鼠巨噬细胞 M1/M2亚型极化的影响。方法分别用脂多糖(LPS)联合干扰素-γ(IFN-γ)和白介素-4(IL-4)诱导小鼠巨噬细胞 M1/M2型极化,用免疫荧光法检测极化结果。在 M1型巨噬细胞中分别加入0.1、1、10μmol/L 替米沙坦,同时设立空白对照组及溶剂对照组,Western blot 法检测各组巨噬细胞亚型标志物诱导性一氧化氮合酶(iNOS)和精氨酸酶Ⅰ(Arg Ⅰ)的表达情况, ELISA 法检测各组培养液上清中 IL-6、IL-10表达情况。结果在 LPS +IFN-γ诱导的小鼠巨噬细胞中 M1型巨噬细胞标志物 iNOS、IL-6的表达水平明显升高,替米沙坦干预后,各干预组 M1型巨噬细胞标志物 iNOS、IL-6的表达水平下降(P <0.05),随着替米沙坦浓度的增加而降低,而代表 M2型巨噬细胞标志物的 Arg

  6. 叉头框转录因子M1在甲状腺乳头状癌组织中的表达及意义%Expression and Significance of Forkhead Box M1 in Papillary Thyroid Carcinoma

    Institute of Scientific and Technical Information of China (English)

    吴文艺; 张丽婷; 王朝阳; 邱建龙; 朱世泽

    2013-01-01

    目的 探讨叉头框转录因子M1(FoxM1)在人类甲状腺乳头状癌组织中的表达及其意义.方法 利用实时荧光定量PCR、Western blot检测20例甲状腺乳头状癌组织及相应的20例癌旁正常甲状腺组织和20例甲状腺腺瘤组织中FoxM1 mRNA和蛋白的表达水平并进行统计学分析.结果 FoxM1 mRNA及蛋白表达在甲状腺乳头状癌组织中显著高于癌旁正常甲状腺组织及甲状腺腺瘤组织(均P< 0.01),癌旁正常甲状腺组织和甲状腺腺瘤组织比较差异无统计学意义(P>0.05),甲状腺乳头状癌有淋巴结转移组高于无淋巴结转移组(P<0.01),包膜侵犯组高于包膜无侵犯组(P<0.01).FoxM1 mRNA及蛋白表达与患者的性别、年龄、肿瘤大小及TNM分期均无关(P>0.05).结论 FoxM1 mRNA及蛋白的异常表达可能与甲状腺乳头状癌的发生发展、淋巴结转移、包膜侵犯有关,有望成为甲状腺乳头状癌诊治中的一个新的标志物.%Objective To investigate the expression and clinical significance of forkhead box M1(FoxM1) in human papillary thyroid carcinoma. Methods Quantitative real-time PCR and Western blot was performed to detect the mRNA and protein expressions of FoxM1 in papillary thyroid carcinoma tissues (20 cases), adjacent normal tissues ( 20 cases), and thyroid adenoma (20 cases); statistical analyze was performed. Results The expressions of FoxM1 mRNA and protein in papillary thyroid carcinoma were significantly higher than that in adjacent normal tissues (P 0.05). The expressions of FoxM1 mRNA and protein were higher in the group with lymph node metastasis than those without lymph node metastasis (P 0.05). Conclusion The abnormal expression of FoxM1 may be associated with the oncogenesis and progress of papillary thyroid carcinoma and lymph node metastasis, capsule invasion, which is expected to become a new marker for diagnosis and treatment of papillary thyroid carcinoma.

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

    Science.gov (United States)

    Fiebig, Anne; Loof, Torsten G; Babbar, Anshu; Itzek, Andreas; Koehorst, Jasper J; Schaap, Peter J; Nitsche-Schmitz, D Patric

    2015-09-01

    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 sequence the whole genome of isolates 5448 and AP1 for comparative analysis. Strain 5448 is known to acquire inactivating mutations in the CovRS two-component system during mouse infection, producing hypervirulent progeny such as 5448AP. Isolates AP1 and 5448AP, more than 5448, caused disseminating infections that became systemic and lethal. SF370 was not pathogenic. Phages caused gross genetic differences and increased the gene content of AP1 by 8% as compared to 5448 and SF370. Each of six examined M1 genomes contained two CRISPR-Cas systems. Phage insertion destroyed a type II CRISPR-Cas system in AP1 and other strains of serotypes M1, M3, M6 and M24, but not in M1 strains 5448, SF370, MGAS5005, A20 or M1 476. A resulting impaired defence against invading genetic elements could have led to the wealth of phages in AP1. AP1 lacks genetic features of the MGAS5005-like clonal complex including the streptodornase that drives selection for hypervirulent clones with inactivated CovRS system. Still, inactivating mutations in covS were a common genetic feature of AP1 and the MGAS5005-like isolate 5448AP. Abolished expression of the cysteine proteinase SpeB, due to CovRS inactivation could be a common cause for hypervirulence of the two isolates. Moreover, an additional protein H-coding gene and a mutation in the regulator gene rofA distinguished AP1 form other M1 isolates. In conclusion, hypervirulence of S. pyogenes M1 in mice is not limited to the MGAS5005-like genotype. Copyright © 2015 Elsevier GmbH. All rights reserved.

  8. 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

  9. Haemophilus ducreyi-induced interleukin-10 promotes a mixed M1 and M2 activation program in human macrophages.

    Science.gov (United States)

    Li, Wei; Katz, Barry P; Spinola, Stanley M

    2012-12-01

    During microbial infection, macrophages are polarized to classically activated (M1) or alternatively activated (M2) cells in response to microbial components and host immune mediators. Proper polarization of macrophages is critical for bacterial clearance. To study the role of macrophage polarization during Haemophilus ducreyi infection, we analyzed a panel of macrophage surface markers in skin biopsy specimens of pustules obtained from experimentally infected volunteers. Lesional macrophages expressed markers characteristic of both M1 and M2 polarization. Monocyte-derived macrophages (MDM) also expressed a mixed M1 and M2 profile of surface markers and cytokines/chemokines upon infection with H. ducreyi in vitro. Endogenous interleukin 10 (IL-10) produced by infected MDM downregulated and enhanced expression of several M1 and M2 markers, respectively. Bacterial uptake, mediated mainly by class A scavenger receptors, and activation of mitogen-activated protein kinase and phosphoinositide 3-kinase signaling pathways were required for H. ducreyi-induced IL-10 production in MDM. Compared to M1 cells, IL-10-polarized M2 cells displayed enhanced phagocytic activity against H. ducreyi and similar bacterial killing. Thus, IL-10-modulated macrophage polarization may contribute to H. ducreyi clearance during human infection.

  10. 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.

  11. Potentiation of M1 Muscarinic Receptor Reverses Plasticity Deficits and Negative and Cognitive Symptoms in a Schizophrenia Mouse Model.

    Science.gov (United States)

    Ghoshal, A; Rook, J M; Dickerson, J W; Roop, G N; Morrison, R D; Jalan-Sakrikar, N; Lamsal, A; Noetzel, M J; Poslusney, M S; Wood, M R; Melancon, B J; Stauffer, S R; Xiang, Z; Daniels, J S; Niswender, C M; Jones, C K; Lindsley, C W; Conn, P J

    2016-01-01

    Schizophrenia patients exhibit deficits in signaling of the M1 subtype of muscarinic acetylcholine receptor (mAChR) in the prefrontal cortex (PFC) and also display impaired cortical long-term depression (LTD). We report that selective activation of the M1 mAChR subtype induces LTD in PFC and that this response is completely lost after repeated administration of phencyclidine (PCP), a mouse model of schizophrenia. Furthermore, discovery of a novel, systemically active M1 positive allosteric modulator (PAM), VU0453595, allowed us to evaluate the impact of selective potentiation of M1 on induction of LTD and behavioral deficits in PCP-treated mice. Interestingly, VU0453595 fully restored impaired LTD as well as deficits in cognitive function and social interaction in these mice. These results provide critical new insights into synaptic changes that may contribute to behavioral deficits in this mouse model and support a role for selective M1 PAMs as a novel approach for the treatment of schizophrenia.

  12. Dissolution and transport of 2,4-DNT and 2,6-DNT from M1 propellant in soil.

    Science.gov (United States)

    Dontsova, Katerina M; Pennington, Judith C; Hayes, Charolett; Simunek, Jiri; Williford, Clint W

    2009-10-01

    Live-fire training exercises can result in particulate propellant contamination on military training ranges and can potentially contaminate ground water. This study was conducted to evaluate dissolution of the 2,4-dinitrotoluene (2,4-DNT) and 2,6-dinitrotoluene (2,6-DNT) from the propellant formulation, M1 (87.6% nitrocellulose, 7.3% 2,4-DNT, 0.57% 2,6-DNT, 1.06% diphenylamine, 3.48% dibutyl phthalate) and their subsequent transport in soil. Batch dissolution studies were followed by saturated column transport experiments. Neat, dissolved 2,4-DNT, and M1 in solid and dissolved forms were used as influent to columns filled with Plymouth loamy sand (mesic, coated Typic Quartzipsamments) from Camp Edwards, MA. Dissolution rates and other fate and transport parameters were determined using the HYDRUS-1D code. M1 dissolution was limited by DNT diffusion from the interior of the pellet, resulting in an exponential decrease in dissolution rate with time. The HYDRUS-1D model accurately described release and transport of 2,4- and 2,6-DNT from M1 propellant. Dissolution rates for M1 in the stirred reactor and column studies were similar, indicating that batch dissolution rates are potentially useful to represent field conditions.

  13. 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...

  14. Different roles for M1 and M2 receptors within perirhinal cortex in object recognition and discrimination.

    Science.gov (United States)

    Bartko, Susan J; Winters, Boyer D; Saksida, Lisa M; Bussey, Timothy J

    2014-04-01

    Recognition and discrimination of objects and individuals are critical cognitive faculties in both humans and non-human animals, and cholinergic transmission has been shown to be essential for both of these functions. In the present study we focused on the role of M1 and M2 muscarinic receptors in perirhinal cortex (PRh)-dependent object recognition and discrimination. The selective M1 antagonists pirenzepine and the snake toxin MT-7, and a selective M2 antagonist, AF-DX 116, were infused directly into PRh. Pre-sample infusions of both pirenzepine and AF-DX 116 significantly impaired object recognition memory in a delay-dependent manner. However, pirenzepine and MT-7, but not AF-DX 116, impaired oddity discrimination performance in a perceptual difficulty-dependent manner. The findings indicate distinct functions for M1 and M2 receptors in object recognition and discrimination.

  15. Association between aflatoxin M1 excreted in human urine samples with the consumption of milk and dairy products.

    Science.gov (United States)

    Mohd Redzwan, Sabran; Rosita, Jamaluddin; Mohd Sokhini, Abdul Mutalib; Nurul Aqilah, Abdul Rahman

    2012-12-01

    This study aimed to find the association between urinary aflatoxin M(1) level and milk and dairy products consumption. Of 160 morning urine samples collected, aflatoxin M(1) was detected in 61.3 % samples (n = 98) [mean ± SD = 0.0234 ± 0.0177 ng/mL; range = 0-0.0747 ng/mL]. Of these positive samples, 67.3 % (n = 66) had levels above the limit of detection. Respondents with intake of milk and dairy products above median (67.79 g/day) had significantly high level of AFM(1) compared to those with low intake. A significant and positive association (φ = 0.286) was found between milk and dairy products consumption and urinary aflatoxin M(1) level.

  16. Observation of M1 resonance in sup 2 sup 0 sup 6 Pb using a highly linear polarized photon beam

    CERN Document Server

    Ohgaki, H; Noguchi, T; Sugiyama, S; Mikado, T; Yamada, K; Suzuki, R; Ohdaira, T; Sei, N; Yamazaki, T

    1999-01-01

    More than twenty M1 states were discovered in sup 2 sup 0 sup 6 Pb from 6.5 to 8.1 MeV with a high-resolution NRF experiment that used a highly linear-polarized photon beam generated by laser-Compton backscattering. The total reduced transition probability of sigma B(M1 arrow up) = 17.4+-5.6 mu sup 2 sub N agreed well with QPM calculation (16.1 mu sup 2 sub N) and previous tagged photon experiment (19 +- 2 mu sup 2 sub N). A fine structure of two bumps at 7.2 and 7.9 MeV which was reproduced reasonably by the QPM calculation was clearly observed in the isovector M1 strength distribution.

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

    Science.gov (United States)

    Vohra, Rupali; Gurubaran, Iswariyaraja Sridevi; Henriksen, Ulrik; Bergersen, Linda Hildegaard; Rasmussen, Lene Juel; Desler, Claus; Skytt, Dorte Marie; Kolko, Miriam

    2017-09-01

    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. Copyright © 2017 Elsevier B.V. and Mitochondria Research Society. All rights reserved.

  18. 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.

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

    Science.gov (United States)

    Kasthurinaidu, Senthilkumar Pitchalu; Ramasamy, Thirumurugan; Ayyavoo, Jayachitra; Dave, Dhvani Kirtikumar; Adroja, Divya Anantray

    2015-01-01

    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.

  20. 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.

  1. Age-related peculiarities of inotropic response of rat myocardium to selective block of M1-cholinoreceptors.

    Science.gov (United States)

    Zefirov, T L; Ziyatdinova, N I; Zefirov, A L

    2013-10-01

    In vitro effect of M1-cholinoreceptor blockade on the cardiac inotropic function was examined in rats aging 1, 3, 6, 8, and 20 weeks. In 1- and 3-week old rat pups, the sympathetic control of the heart has not developed, the age of 7-8 weeks being pubertal. Adult 20-week rats were used as the controls. In rats of all age groups, preliminary blockade of M1-cholinoreceptors did not prevent the inhibitory effect of carbacholine on contractility of the atrial and ventricular myocardium. The inhibitory effect of pirenzepine on the contractile force of ventricular myocardium was revealed in 6-week rats.

  2. Learning from the other limb's experience: sharing the 'trained' M1 representation of the motor sequence knowledge.

    Science.gov (United States)

    Gabitov, Ella; Manor, David; Karni, Avi

    2016-01-01

    Participants were scanned during the untrained-hand performance of a motor sequence, intensively trained a day earlier, and also a similarly constructed but novel, untrained sequence. The superior performance levels for the trained, compared to the untrained sequence, were associated with a greater magnitude of activity within the primary motor cortex (M1), bilaterally, for the trained sequence. The differential responses in the 'trained' M1, ipsilateral to the untrained hand, were positively correlated with experience-related differences in the functional connectivity between the 'trained' M1 and (1) its homologue and (2) the dorsal premotor cortex (PMd) within the contralateral hemisphere. No significant correlation was evident between experience-related differences in M1 - M1 and M1 - PMd connectivity measures. These results suggest that the transfer of sequence-specific information between the two primary motor cortices is predominantly mediated by excitatory mechanisms driven by the 'trained' M1 via two independent neural pathways. Following unimanual training on a novel sequence of movements, sequence-specific performance may improve overnight not only in the trained hand, but also in the hand afforded no actual physical experience. It is not clear, however, how transfer to the untrained hand is achieved. In the present study, we examined whether and how interaction between the two primary motor cortices contributes to the performance of a sequence of movements, extensively trained the day before, by the untrained hand. Accordingly, we studied participants during the untrained-hand performance of a finger-to-thumb opposition sequence (FOS), intensively trained a day earlier (T-FOS), and a similarly constructed, but novel, untrained FOS (U-FOS). Changes in neural signals driven by task performance were assessed using functional magnetic resonance imaging. To minimize potential differences as a result of the rate of sequence execution per se, participants

  3. 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.

  4. Effects of the spin-orbit and tensor interactions on the M1 and E2 excitations in light nuclei

    CERN Document Server

    Fayache, M S; Zamick, L; Von Neumann-Cosel, P; Richter, A

    1996-01-01

    The effects of varying the spin-orbit and tensor components of a realistic interaction on M1 excitation rates and B(E2)'s are studied on nuclei in the 0p and 1s-0d shells. Not only the total M1 but also the spin and orbital parts separately are studied. The single-particle energies are first calculated with the same interaction that is used between the valence nucleons. Later this stringent condition is relaxed somewhat and the 1s level is raised relative to 0d. For nuclei up to ^{28}Si, much better results i.e stronger B(M1) rates are obtained by increasing the strength of the spin-orbit interaction relative to the free value. This is probably also true for ^{32}S, but ^{36}Ar presents some difficulties. The effects of weakening the tensor interaction are also studied. On a more subtle level, the optimum spin-orbit interaction in the lower half of the s-d shell, as far as M1 excitations are concerned, is substantially larger than the difference E(J=3/2^+)_1-E(J=5/2^+)_1=5.2~MeV in ^{17}O. A larger spin-orbit...

  5. Diagonalization of transfer matrix of supersymmetry $u_q(\\hat{sl}(m+1|n+1))$ chain with a boundary

    CERN Document Server

    Kojima, Takeo

    2012-01-01

    We study the supersymmetry $U_q(\\hat{sl}(M+1|N+1))$ analogue of the supersymmetric t-J model with a boundary, in the framework of the algebraic analysis method. We diagonalize the commuting transfer matrix by using the bosonization of the vertex operator associated with the quantum affine supersymmetry.

  6. Occurrence of aflatoxins M(1) and M(2) in milk commercialized in Ribeirão Preto-SP, Brazil.

    Science.gov (United States)

    Garrido, N S; Iha, M H; Santos Ortolani, M R; Duarte Fávaro, R M

    2003-01-01

    Aflatoxins are toxic metabolites found in foods and feeds. When ruminants eat foodstuffs containing aflatoxins B(1) and B(2), these toxins are metabolized and excreted as aflatoxin M(1) and M(2) in milk. The aim was to determine the incidence of these aflatoxins in commercial milk collected from supermarkets in Ribeirão Preto-SP, Brazil, and consisting of 60 ultrahigh temperature (UHT) milk samples and 79 pasteurized milk samples. The milk samples were analysed according to method 986.16 of AOAC International. None of the milk samples analysed were contaminated with aflatoxin M(2), and aflatoxin M(1) was detected in 29 (20.9%) of samples in the range 50-240 ng l(-1). The results show that despite a high occurrence of aflatoxin M(1) in commercial pasteurized and UHT milk sold in Ribeirão Preto in 1999 and 2000, the contamination level of these toxins could not be considered a serious public health problem according to MERCOSUR Technical Regulations. However, levels in 20.9% of the milk samples exceeded the concentration of 50 ng l(-1) permitted by the European Union. Although it is not necessary to continue monitoring the incidence and levels of aflatoxins M(1) and M(2) in milk samples, surveillance could be appropriate.

  7. Structural changes in steel 10Kh9K3V1M1FBR due to creep

    Science.gov (United States)

    Kipelova, A. Yu.; Belyakov, A. N.; Skorobogatykh, V. N.; Shchenkova, I. A.; Kaibyshev, R. O.

    2010-09-01

    The evolution of microstructure in steel 10Kh9K3V1M1FBR during creep and in aging at 600 - 650°C is studied. The results are compared with data for steel P91. The role of cobalt in growth in the long-term strength is considered.

  8. Preparation of three spray-dried milkpowder reference materials for aflatoxin M1 analysis, including packaging and homogeneity control

    NARCIS (Netherlands)

    Egmond; H.P.van; Sizoo; E.A.

    1984-01-01

    Ten behoeve van BCR werden drie partijen melkpoeder bereid, langs natuurlijke weg besmet met aflatoxine M1 op niveau's van 0, ca. 0.3 en ca. 0.9 mug/kg. Van elke partij werden ca. 300 eenheden van elk 25 gram afgevuld in laminaatverpakkingen, die onder N2 werden afgesloten. Onderzoek na afv

  9. Aflatoxin M1 contamination of milk and ice cream in Abeokuta and Odeda local governments of Ogun State, Nigeria.

    Science.gov (United States)

    Atanda, Olusegun; Oguntubo, Adenike; Adejumo, Oloyede; Ikeorah, John; Akpan, Iyang

    2007-07-01

    A survey was undertaken to determine the aflatoxin M(1) contamination of milk and some locally produced dairy products in Abeokuta and Odeda local governments of Ogun State, Nigeria. Samples of human and cow milk, yoghurt, "wara", ice cream and "nono" were collected randomly within the local governments and analysed for aflatoxin M(1) using the two-dimensional TLC. Aflatoxin M(1) contamination in the range of 2.04-4.00 microg l(-1) was noticed only in milk and ice cream. In particular, samples of human milk, cow milk and ice cream recorded high scores of 4.0 microg l(-1), 2.04 microg l(-1) and 2.23 microg l(-1), respectively in Abeokuta local governments and a score of 4.0 microg l(-1) for cow milk in Odeda local government. This indicates a high level contamination in the local governments since the weighted mean concentration of aflatoxin M1 in milk for African diet is 0.002 microg l(-1). Therefore the concentration of AFB1 in feeds which is transformed to AFM1 in milk should be reduced by good manufacturing and good storage practices. Furthermore, there is need for stringent quality control during processing and distribution of these products.

  10. Role of Microglial M1/M2 Polarization in Relapse and Remission of Psychiatric Disorders and Diseases

    Directory of Open Access Journals (Sweden)

    Yutaka Nakagawa

    2014-11-01

    Full Text Available Psychiatric disorders such as schizophrenia and major depressive disorder were thought to be caused by neurotransmitter abnormalities. Patients with these disorders often experience relapse and remission; however the underlying molecular mechanisms of relapse and remission still remain unclear. Recent advanced immunological analyses have revealed that M1/M2 polarization of macrophages plays an important role in controlling the balance between promotion and suppression in inflammation. Microglial cells share certain characteristics with macrophages and contribute to immune-surveillance in the central nervous system (CNS. In this review, we summarize immunoregulatory functions of microglia and discuss a possible role of microglial M1/M2 polarization in relapse and remission of psychiatric disorders and diseases. M1 polarized microglia can produce pro-inflammatory cytokines, reactive oxygen species, and nitric oxide, suggesting that these molecules contribute to dysfunction of neural network in the CNS. Alternatively, M2 polarized microglia express cytokines and receptors that are implicated in inhibiting inflammation and restoring homeostasis. Based on these aspects, we propose a possibility that M1 and M2 microglia are related to relapse and remission, respectively in psychiatric disorders and diseases. Consequently, a target molecule skewing M2 polarization of microglia may provide beneficial therapies for these disorders and diseases in the CNS.

  11. Finite-beta effects on the nonlinear evolution of the (m = 1; n = 1) mode in tokamaks

    Energy Technology Data Exchange (ETDEWEB)

    Holmes, J.A.; Carreras, B.A.; Hicks, H.R.; Lynch, V.E.; Rothe, K.E.

    1982-01-01

    The stability and evolution of ISX-B-like plasmas are numerically studied using a reduced set of resistive magnetohydrodynamic (MHD) equations. For a sequence of equilibria stable to ideal modes, the n = 1 mode changes from a tearing branch to a pressure-driven branch as ..beta../sup p/ is increased. When this mode is unstable at low beta, it is just the (m = 1;n = 1) tearing mode. Higher n modes also become linearly unstable with increasing ..beta../sub p/; they are essentially pressure driven and have a ballooning character. For low values of beta the instability is best described as a ..beta../sub p/ distortion of the (m = 1;n = 1) tearing mode. This mode drives many other helicities through toroidal and nonlinear couplings. As ..beta../sub p/ is increased, the growth of the m = 1 island slows down in time, going from exponential to linear before reconnection occurs. If ..beta../sub p/ is large enough, the island saturates without reconnection. A broad spectrum of other modes, driven by the (m = 1;n = 1) instability, is produced. These results agree with some observed features of MHD activity in ISX-B.

  12. 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.

  13. 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.

  14. Research on detection results of aflatoxin M1 enzyme-linked immune sorbent assay detection kit%黄曲霉毒素M1 ELISA试剂盒的检测效果研究

    Institute of Scientific and Technical Information of China (English)

    李平; 谢体波; 易重任; 魏丽丽; 王大敏; 张建宇; 欧翔; 陈芳; 罗先坤

    2015-01-01

    目的:为验证本公司生产的黄曲霉毒素 M1酶联免疫法(ELISA)检测试剂盒的检测效果。方法用ELISA检测试剂盒对牛奶、酸奶、奶粉和干酪等4种样品中黄曲霉毒素M1的残留量进行检测,并与高效液相色谱荧光检测法进行对照。结果该试剂盒对4种样品的最低检测限分别为0.039、0.192、0.306、0.199μg/kg(L),试剂盒板内板间变异系数均小于5%;对4种样品做加标回收试验,其回收率均在93%~120%之间,变异系数均小于10%;该方法与高效液相色谱法检测实际样品的阴、阳性判断结果一致。结论该方法稳定、可靠、灵敏,可满足食品中黄曲霉毒素M1残留快速检测的需要。%Objective To verify the test effect of aflatoxin M1 enzyme-linked immune sorbent assay (ELISA) detection kit developed by Beijing Kwinbon biotechnology company. Methods The method of ELISA was used to detect the residues of aflatoxin M1 in milk, yoghurt, milk powder and cheese, and compared with high performance liquid chromatography (HPLC). Results The results showed that the minimum detection limitation of the kit for the 4 kinds of samples were 0.039, 0.192, 0.306, and 0.199 μg/kg (L), the coefficient of variation was less than 5%. The recovery of the method was in the range of 93%~120%, and the coefficient of variation was less than 10%. The judgments of positive and negative by ELISA were the same as those of HPLC. Conclusion This method was efficient, reliable and sensitive, and could meet the fast-test for the determination of aflatoxin M1 residues in food.

  15. M1 Site Splitting Due to Next Nearest Neighbor Effects and Ferric Iron in Tetrahedral Site in Clinopyroxene Megacrysts

    Institute of Scientific and Technical Information of China (English)

    李一良; 李玉芝; 等

    1998-01-01

    It is well known that in pyroxene structure,there are two metal sites,M1 and M2.Generally speaking,Ferrous iron in each of these sites would normally be expected to give rise to a doublet,However,anomalies have been found in the relative areas of the peaks in the room temperature spectra of some clinopyroxene(CPX)when the above assignment is followed.According to the calculation of Next Nearest Neighbor configurations of divalent cations in M1,we found that the four configurations of M1 can be divided into two groups.One group is 3Ca configuration that increases with the content of Ca(p.f.u);the other group is made up of three No-3Ca configurations that decrease with the content of Ca.The two groups contribute to the spectrum structure of M1.so in this study we fit two doublets for ferrous iron in M1.Though there were several reports on Fe3+ in tetrahedral site previously,it was not sure that Fe3+ occupies the T site is a universal fact in CPX,despite of the content of Al.We found that the Fe3+ in the T site fitted by Moessbauer spectroscopy is negatively correlated to the Si content in the T site and positively correlated to the Fe3+ in the T site estimated on the supposition that Fe3+ and Al occupy the T site randomly.If it is true.it is important in the modeling of ion exchange geobarometries and geothermomeries.

  16. M1 and M2 macrophage recruitment during tendon regeneration induced by amniotic epithelial cell allotransplantation in ovine.

    Science.gov (United States)

    Mauro, Annunziata; Russo, Valentina; Di Marcantonio, Lisa; Berardinelli, Paolo; Martelli, Alessandra; Muttini, Aurelio; Mattioli, Mauro; Barboni, Barbara

    2016-04-01

    Recently, we have demonstrated that ovine amniotic epithelial cells (oAECs) allotransplanted into experimentally induced tendon lesions are able to stimulate tissue regeneration also by reducing leukocyte infiltration. Amongst leukocytes, macrophages (Mφ) M1 and M2 phenotype cells are known to mediate inflammatory and repairing processes, respectively. In this research it was investigated if, during tendon regeneration induced by AECs allotransplantation, M1Mφ and M2Mφ phenotype cells are recruited and differently distributed within the lesion site. Ovine AECs treated and untreated (Ctr) tendons were explanted at 7, 14, and 28 days and tissue microarchitecture was analyzed together with the distribution and quantification of leukocytes (CD45 positive), Mφ (CD68 pan positive), and M1Mφ (CD86, and IL12b) and M2Mφ (CD206, YM1 and IL10) phenotype related markers. In oAEC transplanted tendons CD45 and CD68 positive cells were always reduced in the lesion site. At day 14, oAEC treated tendons began to recover their microarchitecture, contextually a reduction of M1Mφ markers, mainly distributed close to oAECs, and an increase of M2Mφ markers was evidenced. CD206 positive cells were distributed near the regenerating areas. At day 28 oAECs treated tendons acquired a healthy-like structure with a reduction of M2Mφ. Differently, Ctr tendons maintained a disorganized morphology throughout the experimental time and constantly showed high values of M1Mφ markers. These findings indicate that M2Mφ recruitment could be correlated to tendon regeneration induced by oAECs allotransplantation. Moreover, these results demonstrate oAECs immunomodulatory role also in vivo and support novel insights into their allogeneic use underlying the resolution of tendon fibrosis.

  17. 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.

  18. M/M/1/m系统算子的本征值特性(m=5,6)%The Characteristics of Eigenvalue of M/M/1/m(m =5,6)

    Institute of Scientific and Technical Information of China (English)

    盖平; 高超; 唐慧; 赵立杰

    2010-01-01

    研究了m=5,6时,M/M/1/m算子本征值特性:m=6时相应本征值的代数重为1;m=5,6时,相应的系统算子的非零本征值相互交替;m=6时的最大非零本征值比m=5时更靠近0点.这种特性延续了m=1,2,3,4,5时相应的特性.另外给出了m=5,6时,相应的po(t)图像.

  19. The Lattice Path for Embedded Markov Chain of M/M/1 Queuing System%M/M/1排队系统嵌入Markov链瞬态解的格路径算法

    Institute of Scientific and Technical Information of China (English)

    刘海宁; 屈明双

    2009-01-01

    在定义了生灭过程状态转移的单格与升降格和降升格的基础上,证明了M/M/1排队系统{X(t)t≥0}的嵌入Markov链{X(n)n≥0}的转移概率弱收敛于系统的瞬态解,并利用随机游动的格路径算法求出了该链的转移概率P(i,j,n)的显式算法表达式,从而达到确定M/M/1排队系统{X(t)t≥0}瞬态解的转移概率的目的.

  20. Comparison of HPLC and ELISA Method in Detection of Aflatoxin M1 in Milk%HPLC与ELISA法测定牛奶中黄曲霉毒素M1的比较研究

    Institute of Scientific and Technical Information of China (English)

    胡宏灿; 韩飞; 林悦楷; 卢任杰

    2013-01-01

    The method for detecting aflatoxin Ml in milk was studied by comparison of HPLC and ELISA method. The recovery rates of HPLC were 68%-85% and the recovery rates of ELISA were 97%-109%. Detection results of HPLC and ELISA had good correlation. ELISA method had low cost, rapid detection, it could be used for preliminary screening of aflatoxin Ml. HPLC method was accurate but it had high cost of testing, it is suitable for conclusive evidence of aflatoxin Ml residue.%对HPLC法和ELISA法检测牛奶样品中黄曲霉毒素M1(AFM1)残留量进行了比较,探讨了牛奶中黄曲霉毒素M1的最佳检测方法.结果显示,对于已知加标样品(阳性),HPLC法回收率为68%~85%;ELISA法回收率为97%~109%,HPLC法和ELISA法具有良好的相关性.ELISA法检验成本较低、检测迅速,但可能出现少量的假阳性和假阴性,故可用于待测样品的初筛;HPLC法检测结果准确,但检测费用较高,适用于黄曲霉毒素M1残留的确证.

  1. M/M/1/m系统算子的本征值特性(m=7,8)%The Characteristics of Eigenvalue of M/M/1/m(m = 7,8)

    Institute of Scientific and Technical Information of China (English)

    王伟华; 高超

    2011-01-01

    研究了m=7,8时,M/M/1/m算子本征值特性:相应本征值的代数重为1;m=7,8时,相应的系统算子的非零本征值相互交替;m=8时的最大非零本征值比m=7时更靠近0点.这种特性延续了m=1,2,3,4,5,6时相应的特性.另外给出了m=7,8时,相应的p0(t)图像.%In this paper, studying the characteristic of eigenvalue of M/M/1/m operator,as m = 7, 8. The eigenvalue of every model is simple; The non-zero eigenvalue of the two operator of the system alternate each other. And the maximal nonzero eigenvalue of the latter operator is approximating to zero point. Moreover, the graphs of P0(t) are given, as m = 7, 8.

  2. 牛奶中黄曲霉毒素M1的来源和控制途径%Sources and Ways to Control Aflatoxin M1 in Dairy Milk

    Institute of Scientific and Technical Information of China (English)

    熊江林; 王艳明; 刘建新

    2012-01-01

    Ayatoxins are toxic fungal metabolites found in foods and feeds. Aflatoxins from environment mainly include four subtypes: aflatoxin B1, B2, G1 and aflatoxin G2. Aflatoxin M1, carcinogenic metabolite of aflatoxin B1 in animal body, can be excreted through cow's milk and cause safety issue in dairy milk. In this review article, the sources and conversion of aflatoxin M1 were first discussed. Maximum residue limit (MRL), regulated by main countries and organizations in the world, was compared. Discussion was also made on the detection methods and the possible ways to control aflatoxin M1 in cow milk%黄曲霉毒素(AFs)是存在于食物或饲料中真菌的有毒代谢物,天然产生的AFs主要有AFB1、AFB2、AFG1和AFG2,而AFM1则是AFB1经动物体内转化而来,具有致癌性,可通过牛奶排出,引起牛奶的安全问题.本文综述了牛奶中AFM1的来源与转化,主要国家和组织对奶中AFM1的限量,奶中AFM1的检测方法和控制途径.

  3. Improved energy of the 21.5 keV M1 + E2 nuclear transition in {sup 151}Eu

    Energy Technology Data Exchange (ETDEWEB)

    Inoyatov, A.Kh. [JINR, Laboratory of Nuclear Problems, Dubna, Moscow Region (Russian Federation); National University, Institute of Applied Physics, Tashkent (Uzbekistan); Kovalik, A. [JINR, Laboratory of Nuclear Problems, Dubna, Moscow Region (Russian Federation); Nuclear Physics Institute of the ASCR, Rez near Prague (Czech Republic); Filosofov, D.V.; Perevoshchikov, L.L. [JINR, Laboratory of Nuclear Problems, Dubna, Moscow Region (Russian Federation); Rysavy, M. [Nuclear Physics Institute of the ASCR, Rez near Prague (Czech Republic); Baimukhanova, A. [JINR, Laboratory of Nuclear Problems, Dubna, Moscow Region (Russian Federation); Institute of Nuclear Physics, Almaty (Kazakhstan)

    2016-05-15

    Using internal conversion electron spectroscopy, improved energy 21 541.5±0.5 eV was determined for the 21.5 keV M1+E2 nuclear transition in {sup 151}Eu populated in the electron capture decay of {sup 151}Gd. This value was found to agree well with the present adopted value but is much more accurate. A value of 0.0305±0.0011 derived for the E2 admixture parameter vertical stroke δ(E2/M1) vertical stroke from the measured conversion electron line intensities corresponds to the present adopted value. A possible effect of nuclear structure on the multipolarity of the 21.5 keV transition was also investigated. (orig.)

  4. Short-ranged potential effects on the recurrence spectra of lithium M = 1 atoms in parallel electric and magnetic fields

    Institute of Scientific and Technical Information of China (English)

    Wang Wen-Peng; Li Hong-Yun; Wang Shu-Bao; Lin Sheng-Lu

    2008-01-01

    This paper presents recurrence spectra of highly excited lithium atoms with M = 1 state in parallel electric and magnetic fields at a fixed scaled energy ε = -0.03. Short-ranged potentials including ionic core potential and centrifugal barrier are taken into account. Their effects on the states and photo-absorption spectrum are analysed in detail. This demonstrates that the geometric features of classical orbits are of special importance for modulations of the spectral pattern. Thus the weak polarization as well as the reduction of correlation of electrons induced by short-ranged potentials give rise to the recurrence spectra of lithium M = 1 atoms more compact than that of the M = 0 one, which is in good agreement with the experimental prediction.

  5. Semi-implicit scheme for treating radiation under M1 closure in general relativistic conservative fluid dynamics codes

    CERN Document Server

    Sdowski, Aleksander; Tchekhovskoy, Alexander; Zhu, Yucong

    2012-01-01

    A numerical scheme is described for including radiation in multi-dimensional general-relativistic conservative fluid dynamics codes. In this method, a covariant form of the M1 closure scheme is used to close the radiation moments, and the radiative source terms are treated semi-implicitly in order to handle both optically thin and optically thick regimes. The scheme has been implemented in a conservative general relativistic radiation hydrodynamics code KORAL. The robustness of the code is demonstrated on a number of test problems, including radiative relativistic shock tubes, static radiation pressure supported atmosphere, shadows, beams of light in curved spacetime, and radiative Bondi accretion. The advantages of M1 closure relative to other approaches such as Eddington closure and flux-limited diffusion are discussed, and its limitations are also highlighted.

  6. Genetic Polymorphisms Analysis of Glutathione S-transferase M1 and T1 in Children with Acute Lymphoblastic Leukemia

    Institute of Scientific and Technical Information of China (English)

    王军; 张利; 冯建飞; 王宏; 朱绍先; 胡豫; 李玉香

    2004-01-01

    Summary: The relationship between glutathione S-transferases (GSTs) M1, T1 genotype and childhood acute lymphoblastic leukemia (ALL) was investigated. GSTM1 and GSTT1 genotypes in genomic DNA from 67 children with ALL and 146 healthy controls were analyzed by using the multiplex polymerase chain reaction (PCR). The frequencies of GSTM1, M1-T1 null genotypes in ALL children were significantly higher than in the healthy controls (76.12 % versus 52.74 %, OR=2.856, P<0.001;50. 74 % versus 24. 66 %, OR=3. 148, P<0.001, respectively). However,there was no significant relationship between GSTT1 null genotype and ALL of children (61.19 %versus 49.32 %, OR=1. 621, P>0.05). It was suggested that GSTM1 null genotype might be a risk genotype of childhood ALL, while there as no correlation between GSTT1 null genotype and childhood ALL.

  7. The M1 family of vertebrate aminopeptidases: role of evolutionarily conserved tyrosines in the enzymatic mechanism of aminopeptidase B.

    Science.gov (United States)

    Cadel, Sandrine; Darmon, Cécile; Pernier, Julien; Hervé, Guy; Foulon, Thierry

    2015-02-01

    Aminopeptidase B (Ap-B), a member of the M1 family of Zn(2+)-aminopeptidases, removes basic residues at the NH2-terminus of peptides and is involved in the in vivo proteolytic processing of miniglucagon and cholecystokinin-8. M1 enzymes hydrolyze numerous different peptides and are implicated in many physiological functions. As these enzymes have similar catalytic mechanisms, their respective substrate specificity and/or catalytic efficiency must be based on subtle structural differences at or near the catalytic site. This leads to the hypothesis that each primary structure contains a consensus structural template, strictly necessary for aminopeptidase activity, and a specific amino acid environment localized in or outside the catalytic pocket that finely tunes the substrate specificity and catalytic efficiency of each enzyme. A multiple sequence alignment of M1 peptidases from vertebrates allowed to identify conserved tyrosine amino acids, which are members of this catalytic backbone. In the present work, site-directed mutagenesis and 3D molecular modeling of Ap-B were used to specify the role of four fully (Y281, Y229, Y414, and Y441) and one partially (Y409) conserved residues. Tyrosine to phenylalanine mutations allowed confirming the influence of the hydroxyl groups on the enzyme activity. These groups are implicated in the reaction mechanism (Y414), in substrate specificity and/or catalytic efficiency (Y409), in stabilization of essential amino acids of the active site (Y229, Y409) and potentially in the maintenance of its structural integrity (Y281, Y441). The importance of hydrogen bonds is verified by the Y229H substitution, which preserves the enzyme activity. These data provide new insights into the catalytic mechanism of Ap-B in the M1 family of aminopeptidases. Copyright © 2015 Elsevier B.V. and Société française de biochimie et biologie Moléculaire (SFBBM). All rights reserved.

  8. Downregulation of cystathionine β-synthase/hydrogen sulfide contributes to rotenone-induced microglia polarization toward M1 type.

    Science.gov (United States)

    Du, Chenchen; Jin, Mengmeng; Hong, Yu; Li, Qian; Wang, Xian-Hui; Xu, Jin-Min; Wang, Fen; Zhang, Ye; Jia, Jia; Liu, Chun-Feng; Hu, Li-Fang

    2014-08-22

    Microglia-mediated neuroinflammation is implicated in the pathogenesis of several neurodegenerative disorders. Microglia can be activated and polarized to exert pro- or anti-inflammatory roles in response to specific stimulus. Rotenone is an environmental toxin that has been shown to activate microglia and neuroinflammation. However, the effects and mechanisms of rotenone on microglia polarization are poorly studied. In the present study, we demonstrated that rotenone enhanced the levels of M1 phenotypic genes including TNF-α, iNOS and COX-2/PGE2 but reduced that of M2 markers such as Ym1/2 and IL-10 in mouse primary and immortalized microglia. Moreover, the transcription and protein expression of cystathionine-β-synthase (CBS), as well as hydrogen sulfide (H2S) production were decreased in rotenone-treated primary microglia. Elevating endogenous H2S via CBS over-expression in immortalized microglia not only reduced the expression of pro-inflammatory M1 genes, but also enhanced the anti-inflammatory M2 marker IL-10 production in response to rotenone stimulation as compared to vector-transfected cells. Similarly, pretreatment with H2S donor NaHS (50, 100 and 500μmol/L) attenuated the increases of M1 gene expression triggered by rotenone treatment, and enhanced the M2 gene Ym1/2 expression in mouse primary microglia. In addition, we observed reactive oxygen species (ROS) scavenger N-acetyl-l-cysteine reversed the down-regulation of CBS and H2S generation caused by rotenone in microglia. NaHS pretreatment also decreased the ROS formation in rotenone-stimulated microglia. Taken together, these results reveal that probably via triggering ROS formation, rotenone suppressed the CBS-H2S pathway and thus promoted microglia polarization toward M1 pro-inflammatory phenotype.

  9. 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.

    2013-01-01

    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. PMID:23793893

  10. Autoantibody against transient receptor potential M1 cation channels of retinal ON bipolar cells in paraneoplastic vitelliform retinopathy

    Directory of Open Access Journals (Sweden)

    Wang Yujuan

    2012-11-01

    Full Text Available Abstract Background Paraneoplastic retinopathy is caused by the cross-reaction of neoplasm-directed autoantibodies against retinal antigens and results in retinal damage. Paraneoplastic vitelliform retinopathy, a presumed paraneoplastic retinopathy with features of atypical melanoma-associated retinopathy, has recently been reported in patients with metastatic melanoma. Ocular ultrastructure and its autoantibody localization of paraneoplastic vitelliform retinopathy are still indefinable. This is the first report of anti-transient receptor potential M1 antibody directly against human retinal bipolar dendritic tips in a melanoma patient with paraneoplastic vitelliform retinopathy. Case presentation We present a pair of postmortem eyes of an 80-year-old male with metastatic cutaneous melanoma, who developed paraneoplastic vitelliform retinopathy. The autopsied eyes were examined with light microscopy, immunohistochemistry, and transmission electron microscopy. Microscopically, the inner nuclear layer and outer plexiform layer were the most affected retinal structures, with local thinning. The lesions extended to the outer nuclear layer, resulting in focal retinal degeneration, edema, and atrophy. No active inflammation or melanoma cells were observed. Immunohistochemistry showed tightly compact bipolar cell nuclei (protein kinase C alpha/calbindin positive with blur/loss of ON bipolar cell dendritic tips (transient receptor potential M1 positive in diffusely condensed outer plexiform layer. The metastatic melanoma cells in his lung also showed immunoreactivity against transient receptor potential M1 antibody. Transmission electron microscopy illustrated degenerated inner nuclear layer with disintegration of cells and loss of cytoplasmic organelles. These cells contained many lysosomal and autophagous bodies and damaged mitochondria. Their nuclei appeared pyknotic and fragmentary. The synapses in the outer plexiform layer were extensively

  11. Exploration of the orthosteric/allosteric interface in human M1 muscarinic receptors by bitopic fluorescent ligands.

    Science.gov (United States)

    Daval, Sandrine B; Kellenberger, Esther; Bonnet, Dominique; Utard, Valérie; Galzi, Jean-Luc; Ilien, Brigitte

    2013-07-01

    Bitopic binding properties apply to a variety of muscarinic compounds that span and simultaneously bind to both the orthosteric and allosteric receptor sites. We provide evidence that fluorescent pirenzepine derivatives, with the M1 antagonist fused to the boron-dipyrromethene [Bodipy (558/568)] fluorophore via spacers of varying lengths, exhibit orthosteric/allosteric binding properties at muscarinic M1 receptors. This behavior was inferred from a combination of functional, radioligand, and fluorescence resonance energy transfer binding experiments performed under equilibrium and kinetic conditions on enhanced green fluorescent protein-fused M1 receptors. Although displaying a common orthosteric component, the fluorescent compounds inherit bitopic properties from a linker-guided positioning of their Bodipy moiety within the M1 allosteric vestibule. Depending on linker length, the fluorophore is allowed to reach neighboring allosteric domains, overlapping or not with the classic gallamine site, but distinct from the allosteric indolocarbazole "WIN" site. Site-directed mutagenesis, as well as molecular modeling and ligand docking studies based on recently solved muscarinic receptor structures, further support the definition of two groups of Bodipy-pirenzepine derivatives exhibiting distinct allosteric binding poses. Thus, the linker may dictate pharmacological outcomes for bitopic molecules that are hardly predictable from the properties of individual orthosteric and allosteric building blocks. Our findings also demonstrate that the fusion of a fluorophore to an orthosteric ligand is not neutral, as it may confer, unless carefully controlled, unexpected properties to the resultant fluorescent tracer. Altogether, this study illustrates the importance of a "multifacet" experimental approach to unravel and validate bitopic ligand binding mechanisms.

  12. Dynamic Regulation of Quaternary Organization of the M1 Muscarinic Receptor by Subtype-selective Antagonist Drugs*

    Science.gov (United States)

    Pediani, John D.; Ward, Richard J.; Godin, Antoine G.; Marsango, Sara

    2016-01-01

    Although rhodopsin-like G protein-coupled receptors can exist as both monomers and non-covalently associated dimers/oligomers, the steady-state proportion of each form and whether this is regulated by receptor ligands are unknown. Herein we address these topics for the M1 muscarinic acetylcholine receptor, a key molecular target for novel cognition enhancers, by using spatial intensity distribution analysis. This method can measure fluorescent particle concentration and assess oligomerization states of proteins within defined regions of living cells. Imaging and analysis of the basolateral surface of cells expressing some 50 molecules·μm−2 human muscarinic M1 receptor identified a ∼75:25 mixture of receptor monomers and dimers/oligomers. Both sustained and shorter term treatment with the selective M1 antagonist pirenzepine resulted in a large shift in the distribution of receptor species to favor the dimeric/oligomeric state. Although sustained treatment with pirenzepine also resulted in marked up-regulation of the receptor, simple mass action effects were not the basis for ligand-induced stabilization of receptor dimers/oligomers. The related antagonist telenzepine also produced stabilization and enrichment of the M1 receptor dimer population, but the receptor subtype non-selective antagonists atropine and N-methylscopolamine did not. In contrast, neither pirenzepine nor telenzepine altered the quaternary organization of the related M3 muscarinic receptor. These data provide unique insights into the selective capacity of receptor ligands to promote and/or stabilize receptor dimers/oligomers and demonstrate that the dynamics of ligand regulation of the quaternary organization of G protein-coupled receptors is markedly more complex than previously appreciated. This may have major implications for receptor function and behavior. PMID:27080256

  13. Dynamic Regulation of Quaternary Organization of the M1 Muscarinic Receptor by Subtype-selective Antagonist Drugs.

    Science.gov (United States)

    Pediani, John D; Ward, Richard J; Godin, Antoine G; Marsango, Sara; Milligan, Graeme

    2016-06-17

    Although rhodopsin-like G protein-coupled receptors can exist as both monomers and non-covalently associated dimers/oligomers, the steady-state proportion of each form and whether this is regulated by receptor ligands are unknown. Herein we address these topics for the M1 muscarinic acetylcholine receptor, a key molecular target for novel cognition enhancers, by using spatial intensity distribution analysis. This method can measure fluorescent particle concentration and assess oligomerization states of proteins within defined regions of living cells. Imaging and analysis of the basolateral surface of cells expressing some 50 molecules·μm(-2) human muscarinic M1 receptor identified a ∼75:25 mixture of receptor monomers and dimers/oligomers. Both sustained and shorter term treatment with the selective M1 antagonist pirenzepine resulted in a large shift in the distribution of receptor species to favor the dimeric/oligomeric state. Although sustained treatment with pirenzepine also resulted in marked up-regulation of the receptor, simple mass action effects were not the basis for ligand-induced stabilization of receptor dimers/oligomers. The related antagonist telenzepine also produced stabilization and enrichment of the M1 receptor dimer population, but the receptor subtype non-selective antagonists atropine and N-methylscopolamine did not. In contrast, neither pirenzepine nor telenzepine altered the quaternary organization of the related M3 muscarinic receptor. These data provide unique insights into the selective capacity of receptor ligands to promote and/or stabilize receptor dimers/oligomers and demonstrate that the dynamics of ligand regulation of the quaternary organization of G protein-coupled receptors is markedly more complex than previously appreciated. This may have major implications for receptor function and behavior. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. In-field evaluation of clinoptilolite feeding efficacy on the reduction of milk aflatoxin M1 concentration in dairy cattle

    OpenAIRE

    Katsoulos, Panagiotis D.; Karatzia, Maria A.; Boscos, Constantinos; Wolf, Petra; Karatzias, Harilaos

    2016-01-01

    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 ...

  15. A scheme for radiation pressure and photon diffusion with the M1 closure in RAMSES-RT

    OpenAIRE

    Rosdahl, J.; Teyssier, Romain

    2015-01-01

    We describe and test an updated version of radiation-hydrodynamics in the RAMSES code, that includes three new features: (i) radiation pressure on gas, (ii) accurate treatment of radiation diffusion in an unresolved optically thick medium, and (iii) relativistic corrections that account for Doppler effects and work done by the radiation to first order in v/c. We validate the implementation in a series of tests, which include a morphological assessment of the M1 closure for the Eddington tenso...

  16. Gamma-Rays and E0 and M1+E0 Transitions in $^{152}Tb \\to ^{152}$Gd Decay

    CERN Document Server

    Adam, J; Honusek, M; Kalinnikov, V G; Mrazek, J; Pronskikh, V S; Caloun, P; Lebedev, N A; Stegailov, V I; Tsoupko-Sitnikov, V M

    2001-01-01

    The decay of ^{152}Tb has been investigated by means of measurements of single gamma-spectra. The 704 transitions were observed, of which 347 were identified to the decay of ^{152}Tb for the first time. Using the more precise and full data about intensities of gamma-transitions and previously reported conversion electron intensities the E0 or M1+E0 multipolarities were established for several transitions.

  17. 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.

  18. Active vitamin D prevents podocyte injury via regulation of macrophage M1 and M2 phenotype in diabetic nephropathy rats

    Institute of Scientific and Technical Information of China (English)

    郭银凤

    2014-01-01

    Objective To investigate the effect of active vitamin D(VD)on macrophage M1 and M2 phenotype and its role in protecting podocyte impairment in diabetic nephropathy(DN).Methods Diabetes mellitus rats were established by intraperitoneal injection with streptozocin.Rats were randomly divided into four groups:normal-1(NC-1,n=8),normal-2(NC-2,n=8,normal rats treated with calcitriol 0.1μg·kg-1·d-1by gavages),

  19. A Study on the Occurrence of Aflatoxin M1 in Raw and Pasteurized Milk Produced in Rafsanjan, Iran

    OpenAIRE

    FaAkrami Mohajeri Akrami Mohajeri; Asieh Amiri; Hossein Khorramdel Azad; Zahra Ahmadi; Zahra Asadollahi; Mohsen Rezaeian; Fallah, Aziz A.; Seyed Razi Ghalebi

    2015-01-01

    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...

  20. FoxM1 Promotes Stemness and Radio-Resistance of Glioblastoma by Regulating the Master Stem Cell Regulator Sox2.

    Science.gov (United States)

    Lee, Yeri; Kim, Kang Ho; Kim, Dong Geon; Cho, Hee Jin; Kim, Yeonghwan; Rheey, Jinguen; Shin, Kayoung; Seo, Yun Jee; Choi, Yeon-Sook; Lee, Jung-Il; Lee, Jeongwu; Joo, Kyeung Min; Nam, Do-Hyun

    2015-01-01

    Glioblastoma (GBM) is the most aggressive and most lethal brain tumor. As current standard therapy consisting of surgery and chemo-irradiation provides limited benefit for GBM patients, novel therapeutic options are urgently required. Forkhead box M1 (FoxM1) transcription factor is an oncogenic regulator that promotes the proliferation, survival, and treatment resistance of various human cancers. The roles of FoxM1 in GBM remain incompletely understood, due in part to pleotropic nature of the FoxM1 pathway. Here, we show the roles of FoxM1 in GBM stem cell maintenance and radioresistance. ShRNA-mediated FoxM1 inhibition significantly impeded clonogenic growth and survival of patient-derived primary GBM cells with marked downregulation of Sox2, a master regulator of stem cell phenotype. Ectopic expression of Sox2 partially rescued FoxM1 inhibition-mediated effects. Conversely, FoxM1 overexpression upregulated Sox2 expression and promoted clonogenic growth of GBM cells. These data, with a direct binding of FoxM1 in the Sox2 promoter region in GBM cells, suggest that FoxM1 regulates stemness of primary GBM cells via Sox2. We also found significant increases in FoxM1 and Sox2 expression in GBM cells after irradiation both in vitro and in vivo orthotopic tumor models. Notably, genetic or a small-molecule FoxM1 inhibitor-mediated FoxM1 targeting significantly sensitized GBM cells to irradiation, accompanying with Sox2 downregulation. Finally, FoxM1 inhibition combined with irradiation in a patient GBM-derived orthotopic model significantly impeded tumor growth and prolonged the survival of tumor bearing mice. Taken together, these results indicate that the FoxM1-Sox2 signaling axis promotes clonogenic growth and radiation resistance of GBM, and suggest that FoxM1 targeting combined with irradiation is a potentially effective therapeutic approach for GBM.

  1. Higher Levels of Aflatoxin M1 Contamination and Poorer Composition of Milk Supplied by Informal Milk Marketing Chains in Pakistan.

    Science.gov (United States)

    Aslam, Naveed; Tipu, Muhammad Yasin; Ishaq, Muhammad; Cowling, Ann; McGill, David; Warriach, Hassan Mahmood; Wynn, Peter

    2016-12-05

    The present study was conducted to observe the seasonal variation in aflatoxin M1 and nutritional quality of milk along informal marketing chains. Milk samples (485) were collected from three different chains over a period of one year. The average concentrations of aflatoxin M1 during the autumn and monsoon seasons (2.60 and 2.59 ppb) were found to be significantly higher (standard error of the difference, SED = 0.21: p = 0.003) than in the summer (1.93 ppb). The percentage of added water in milk was significantly lower (SED = 1.54: p marketing chain. There was no difference (p = 0.178) in concentration of aflatoxin M1 in milk collected from the farmers (2.12 ppb), small collectors (2.23 ppb), large collectors (2.36 ppb) and retailers (2.58 ppb). The high levels of contamination found in this study, which exceed the standards set by European Union (0.05 ppb) and USFDA (0.5 ppb), demand radical intervention by regulatory authorities and mass awareness of the consequences for consumer health and safety.

  2. A Genetic Switch to Hypervirulence Reduces Colonization Phenotypes of the Globally Disseminated Group A Streptococcus M1T1 Clone

    Science.gov (United States)

    Hollands, Andrew; Pence, Morgan A.; Timmer, Anjuli M.; Osvath, Sarah R.; Turnbull, Lynne; Whitchurch, Cynthia B.; Walker, Mark J.; Nizet, Victor

    2010-01-01

    Background The recent resurgence of invasive group A streptococcal disease has been paralleled by the emergence of the M1T1 clone. Recently, invasive disease initiation to has been linked to mutations in the covR/S two-compnent regulator. Here we investigate if a fitness cost is associated with covS mutation that counterbalances hypervirulence. Methods Wild-type M1T1 GAS and an isogenic covS mutant derived from animal passage were compared for adherence to human laryngeal epithelial cells, keratinocytes or fibronectin, biofilm formation, and binding to intact mouse skin. Targeted mutagenesis of capsule expression from both strains was performed for analysis of its unique contribution to the observed phenotypes. Results The covS mutant bacteria showed reduced capacity to bind to epithelial cell layers as a consequence of increased capsule expression. The covS mutant strain also had reduced capacity to bind fibronectin and to form biofilms on plastic and epithelial cell layers. A defect in skin adherence of the covS mutant strain was demonstrated in a murine model. Conclusions Reduced colonization capacity provides a potential explanation as to why the covS mutation conferring hypervirulence has not become fixed in the globally-disseminated M1T1 GAS clone, but rather may arise anew under innate immune selection in individual patients. PMID:20507231

  3. Genetic switch to hypervirulence reduces colonization phenotypes of the globally disseminated group A streptococcus M1T1 clone.

    Science.gov (United States)

    Hollands, Andrew; Pence, Morgan A; Timmer, Anjuli M; Osvath, Sarah R; Turnbull, Lynne; Whitchurch, Cynthia B; Walker, Mark J; Nizet, Victor

    2010-07-01

    The recent resurgence of invasive group A streptococcal disease has been paralleled by the emergence of the M1T1 clone. Recently, invasive disease initiation has been linked to mutations in the covR/S 2-component regulator. We investigated whether a fitness cost is associated with the covS mutation that counterbalances hypervirulence. Wild-type M1T1 group A Streptococcus and an isogenic covS-mutant strain derived from animal passage were compared for adherence to human laryngeal epithelial cells, human keratinocytes, or fibronectin; biofilm formation; and binding to intact mouse skin. Targeted mutagenesis of capsule expression of both strains was performed for analysis of its unique contribution to the observed phenotypes. The covS-mutant bacteria showed reduced capacity to bind to epithelial cell layers as a consequence of increased capsule expression. The covS-mutant strain also had reduced capacity to bind fibronectin and to form biofilms on plastic and epithelial cell layers. A defect in skin adherence of the covS-mutant strain was demonstrated in a murine model. Reduced colonization capacity provides a potential explanation for why the covS mutation, which confers hypervirulence, has not become fixed in the globally disseminated M1T1 group A Streptococcus clone, but rather may arise anew under innate immune selection in individual patients.

  4. Implications for Damage Recognition during Dpo4-Mediated Mutagenic Bypass of m1G and m3C Lesions

    Energy Technology Data Exchange (ETDEWEB)

    Rechkoblit, Olga; Delaney, James C.; Essigmann, John M.; Patel, Dinshaw J. (MIT); (MSKCC)

    2012-05-08

    DNA is susceptible to alkylation damage by a number of environmental agents that modify the Watson-Crick edge of the bases. Such lesions, if not repaired, may be bypassed by Y-family DNA polymerases. The bypass polymerase Dpo4 is strongly inhibited by 1-methylguanine (m1G) and 3-methylcytosine (m3C), with nucleotide incorporation opposite these lesions being predominantly mutagenic. Further, extension after insertion of both correct and incorrect bases, introduces additional base substitution and deletion errors. Crystal structures of the Dpo4 ternary extension complexes with correct and mismatched 3'-terminal primer bases opposite the lesions reveal that both m1G and m3C remain positioned within the DNA template/primer helix. However, both correct and incorrect pairing partners exhibit pronounced primer terminal nucleotide distortion, being primarily evicted from the DNA helix when opposite m1G or misaligned when pairing with m3C. Our studies provide insights into mechanisms related to hindered and mutagenic bypass of methylated lesions and models associated with damage recognition by repair demethylases.

  5. Differential effects of M1 muscarinic receptor blockade and nicotinic receptor blockade in the dorsomedial striatum on response reversal learning

    Science.gov (United States)

    Tzavos, Arianna; Jih, Jane; Ragozzino, Michael E.

    2011-01-01

    The present studies determined whether blockade of M1-like muscarinic or nicotinic cholinergic receptors in the dorsomedial striatum affects acquisition or reversal learning of a response discrimination. Testing occurred in a modified cross-maze across two consecutive sessions. In the acquisition phase, a rat learned to turn to the left or to the right. In the reversal learning phase, a rat learned to turn in the opposite direction as required during acquisition. Experiment 1 investigated the effects of the M1-like muscarinic receptor antagonist, pirenzepine infused into the dorsomedial striatum on acquisition and reversal learning. Experiment 2 examined the effects of the nicotinic cholinergic antagonist, mecamylamine injected into the dorsomedial striatum on acquisition and reversal learning. Bilateral injections of pirenzepine at 10 µg, but not 1 µg, selectively impaired reversal learning. Analysis of the errors indicated that pirenzepine treatment did not impair the initial shift, but increased reversions back to the original response choice following the initial shift. Bilateral injections of mecamylamine, 6 or 18 µg, did not affect acquisition or reversal learning. The results suggest that activation of M1 muscarinic cholinergic receptors, but not nicotinic cholinergic receptors, in the dorsomedial striatum is important for facilitating the flexible shifting of response patterns. PMID:15302131

  6. [Determination of virginiamycin M1, in feeds by ultra high performance liquid chromatography-tandem mass spectrometry].

    Science.gov (United States)

    Huang, Yonghui

    2011-10-01

    A comprehensive analytical method based on ultra high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been developed for the determination of virginiamycin M1 in feeds. The sample was extracted twice by ultrasonic extraction with ace-tonitrile-0.2% (v/v) formic acid (8:2, v/v). The chromatographic separation was achieved with a BEH C18 column and acetonitrile-0. 3% (v/v) formic acid (35: 65, v/v) as the mobile phase. The identification and quantification of the analyte were carried out on electrospray ionization MS/MS in a multiple reaction monitoring (MRM) mode. The correlation coefficient (r) of virginiamycin M1 was 0. 999 5 in the linear range of 0. 3 -226. 6 microg/L. The detection limit (S/ N = 3) and quantification limit (S/N = 10) of virginiamycin M1 were 2 microg/kg and 7 microg/kg, respectively. The average spiked recoveries were in the range of 82. 6% to 102. 7% with the relative standard deviations (RSDs) of 0.9% - 10.5%. The results demonstrate that the proposed method is simple, sensitive, repeatable and suitable for the testing of virginiamycin M, in feeds.

  7. Higher Levels of Aflatoxin M1 Contamination and Poorer Composition of Milk Supplied by Informal Milk Marketing Chains in Pakistan

    Science.gov (United States)

    Aslam, Naveed; Tipu, Muhammad Yasin; Ishaq, Muhammad; Cowling, Ann; McGill, David; Warriach, Hassan Mahmood; Wynn, Peter

    2016-01-01

    The present study was conducted to observe the seasonal variation in aflatoxin M1 and nutritional quality of milk along informal marketing chains. Milk samples (485) were collected from three different chains over a period of one year. The average concentrations of aflatoxin M1 during the autumn and monsoon seasons (2.60 and 2.59 ppb) were found to be significantly higher (standard error of the difference, SED = 0.21: p = 0.003) than in the summer (1.93 ppb). The percentage of added water in milk was significantly lower (SED = 1.54: p < 0.001) in summer (18.59%) than in the monsoon season (26.39%). There was a significantly different (SED = 2.38: p < 0.001) mean percentage of water added by farmers (6.23%), small collectors (14.97%), large collectors (27.96%) and retailers (34.52%). This was reflected in changes in milk quality along the marketing chain. There was no difference (p = 0.178) in concentration of aflatoxin M1 in milk collected from the farmers (2.12 ppb), small collectors (2.23 ppb), large collectors (2.36 ppb) and retailers (2.58 ppb). The high levels of contamination found in this study, which exceed the standards set by European Union (0.05 ppb) and USFDA (0.5 ppb), demand radical intervention by regulatory authorities and mass awareness of the consequences for consumer health and safety. PMID:27929386

  8. Higher Levels of Aflatoxin M1 Contamination and Poorer Composition of Milk Supplied by Informal Milk Marketing Chains in Pakistan

    Directory of Open Access Journals (Sweden)

    Naveed Aslam

    2016-12-01

    Full Text Available The present study was conducted to observe the seasonal variation in aflatoxin M1 and nutritional quality of milk along informal marketing chains. Milk samples (485 were collected from three different chains over a period of one year. The average concentrations of aflatoxin M1 during the autumn and monsoon seasons (2.60 and 2.59 ppb were found to be significantly higher (standard error of the difference, SED = 0.21: p = 0.003 than in the summer (1.93 ppb. The percentage of added water in milk was significantly lower (SED = 1.54: p < 0.001 in summer (18.59% than in the monsoon season (26.39%. There was a significantly different (SED = 2.38: p < 0.001 mean percentage of water added by farmers (6.23%, small collectors (14.97%, large collectors (27.96% and retailers (34.52%. This was reflected in changes in milk quality along the marketing chain. There was no difference (p = 0.178 in concentration of aflatoxin M1 in milk collected from the farmers (2.12 ppb, small collectors (2.23 ppb, large collectors (2.36 ppb and retailers (2.58 ppb. The high levels of contamination found in this study, which exceed the standards set by European Union (0.05 ppb and USFDA (0.5 ppb, demand radical intervention by regulatory authorities and mass awareness of the consequences for consumer health and safety.

  9. Uptake, elimination and fish bioconcentration factors for the persistent hexa- and nonachlorobornanes- M1 and P-50

    Energy Technology Data Exchange (ETDEWEB)

    Maruya, K. [Skidaway Inst. of Oceanography, Savannah, GA (United States); Warttinger, U. [Fachhochschule fuer Technik und Gestaltung, Mannheim (Germany)

    2004-09-15

    Knowledge of the uptake and elimination kinetics of chlorobornane (toxaphene) residue congeners by aquatic organisms is key to understanding their environmental fate. Most work to date has focused on a select few octa- and nonachlorinated congeners that are globally distributed and persistent. However, recent evidence suggests that lower chlorinated toxaphene residue congeners, such as 2-exo, 5-endo, 6-exo, 8c, 9b, 10a-hexachlorobornane (aka Hx-Sed; B6-923 or M1), are also detected in polar regions and thus may survive long range transport. In this study, we followed the uptake and elimination of M1 by a model fish and compared rates with that for 2- endo,3-exo,5-endo,6-exo,8,8,9,10,10-nonachlorobornane (aka B9-1679 or P-50), a known persistent congener. From these experiments, we estimated the steady state bioconcentration factor (BCF) for M1 and compared our value with reported modeled and field-based values for toxaphene congeners with a similar degree of chlorination.

  10. Echinacea purpurea Extract Polarizes M1 Macrophages in Murine Bone Marrow-Derived Macrophages Through the Activation of JNK.

    Science.gov (United States)

    Fu, Aikun; Wang, Yang; Wu, Yanping; Chen, Hongliang; Zheng, Shasha; Li, Yali; Xu, Xin; Li, Weifen

    2017-09-01

    Echinacea purpurea is an indigenous North American purple cone flower used by North Americans for treatment of various infectious diseases and wounds. This study investigated the effect of polysaccharide enriched extract of Echinacea purpurea (EE) on the polarization of macrophages. The results showed that 100 µg/mL of EE could markedly activate the macrophage by increasing the expression of CD80, CD86, and MHCII molecules. Meanwhile, EE upregulated the markers of classically activated macrophages (M1) such as CCR7 and the production of IL-1β, IL-6, IL-12p70, TNF-αand NO. The functional tests showed that EE enhanced the phagocytic and intracellular bactericidal activity of macrophage against ST. Furthermore, we demonstrated that JNK are required for EE-induced NO and M1-related cytokines production. Together, these results demonstrated that EE can polarize macrophages towards M1 phenotype, which is dependent on the JNK signaling pathways. J. Cell. Biochem. 118: 2664-2671, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  11. 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

    2017-03-03

    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.

  12. Fast-timing study of the l -forbidden 1 /2+→3 /2+ M 1 transition in 129Sn

    Science.gov (United States)

    Licǎ, R.; Mach, H.; Fraile, L. M.; Gargano, A.; Borge, M. J. G.; Mǎrginean, N.; Sotty, C. O.; Vedia, V.; Andreyev, A. N.; Benzoni, G.; Bomans, P.; Borcea, R.; Coraggio, L.; Costache, C.; De Witte, H.; Flavigny, F.; Fynbo, H.; Gaffney, L. P.; Greenlees, P. T.; Harkness-Brennan, L. J.; Huyse, M.; Ibáñez, P.; Judson, D. S.; Konki, J.; Korgul, A.; Kröll, T.; Kurcewicz, J.; Lalkovski, S.; Lazarus, I.; Lund, M. V.; Madurga, M.; Mǎrginean, R.; Marroquín, I.; Mihai, C.; Mihai, R. E.; Morales, A. I.; Nácher, E.; Negret, A.; Page, R. D.; Pakarinen, J.; Pascu, S.; Paziy, V.; Perea, A.; Pérez-Liva, M.; Picado, E.; Pucknell, V.; Rapisarda, E.; Rahkila, P.; Rotaru, F.; Swartz, J. A.; Tengblad, O.; Van Duppen, P.; Vidal, M.; Wadsworth, R.; Walters, W. B.; Warr, N.; IDS Collaboration

    2016-04-01

    The levels in 129Sn populated from the β- decay of 129In isomers were investigated at the ISOLDE facility of CERN using the newly commissioned ISOLDE Decay Station (IDS). The lowest 1 /2+ state and the 3 /2+ ground state in 129Sn are expected to have configurations dominated by the neutron s1 /2 (l =0 ) and d3 /2 (l =2 ) single-particle states, respectively. Consequently, these states should be connected by a somewhat slow l -forbidden M 1 transition. Using fast-timing spectroscopy we have measured the half-life of the 1 /2+ 315.3-keV state, T1 /2= 19(10) ps, which corresponds to a moderately fast M 1 transition. Shell-model calculations using the CD-Bonn effective interaction, with standard effective charges and g factors, predict a 4-ns half-life for this level. We can reconcile the shell-model calculations to the measured T1 /2 value by the renormalization of the M 1 effective operator for neutron holes.

  13. Contribution of Secreted NADase and Streptolysin O to the Pathogenesis of Epidemic Serotype M1 Streptococcus pyogenes Infections.

    Science.gov (United States)

    Zhu, Luchang; Olsen, Randall J; Lee, Jessica D; Porter, Adeline R; DeLeo, Frank R; Musser, James M

    2017-03-01

    Streptococcus pyogenes secretes many toxins that facilitate human colonization, invasion, and dissemination. NADase (SPN) and streptolysin O (SLO) are two toxins that play important roles in pathogenesis. We previously showed that increased production of SPN and SLO in epidemic serotype M1 and M89 S. pyogenes strains is associated with rapid intercontinental spread and enhanced virulence. The biological functions of SPN and SLO have been extensively studied using eukaryotic cell lines, but the relative contribution of each of these two toxins to pathogenesis of epidemic M1 or M89 strains remains unexplored. Herein, using a genetically representative epidemic M1 strain and a panel of isogenic mutant derivative strains, we evaluated the relative contributions of SPN and SLO toxins to virulence in mouse models of necrotizing myositis, bacteremia, and skin and soft tissue infection. We found that isogenic mutants lacking SPN, SLO, and both toxins are equally impaired in ability to cause necrotizing myositis. In addition, mutants lacking either SPN or SLO are significantly attenuated in the bacteremia and soft tissue infection models, and the mutant strain lacking production of both toxins is further attenuated. The mutant strain lacking both SPN and SLO production is severely attenuated in ability to resist killing by human polymorphonuclear leukocytes. We conclude that both SPN and SLO contribute significantly to S. pyogenes pathogenesis in these virulence assays. Copyright © 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.

  14. Macrophages Undergo M1-to-M2 Transition in Adipose Tissue Regeneration in a Rat Tissue Engineering Model.

    Science.gov (United States)

    Li, Zhijin; Xu, Fangfang; Wang, Zhifa; Dai, Taiqiang; Ma, Chao; Liu, Bin; Liu, Yanpu

    2016-10-01

    Macrophages are involved in the full processes of tissue healing or regeneration and play an important role in the regeneration of a variety of tissues. Although recent evidence suggests the role of different macrophage phenotypes in adipose tissue expansion, metabolism, and remodeling, the spectrum of macrophage phenotype in the adipose tissue engineering field remains unknown. The present study established a rat model of adipose tissue regeneration using a tissue engineering chamber. Macrophage phenotypes were assessed during the regenerative process in the model. Neo-adipose tissue was generated 6 weeks after implantation. Macrophages were obvious in the chamber constructs 3 days after implantation, peaked at day 7, and significantly decreased thereafter. At day 3, macrophages were predominantly M1 macrophages (CCR7+), and there were few M2 macrophages (CD206+). At day 7, the percentage of M2 macrophages significantly increased and remained stable at day 14. M2 macrophages became the predominant macrophage population at 42 days. Enzyme-linked immunosorbent assay demonstrated transition of cytokines from pro-inflammatory to anti-inflammatory, which was consistent with the transition of macrophage phenotype from M1 to M2. These results showed distinct transition of macrophage phenotypes from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 in adipose tissue regeneration in our tissue engineering model. This study provides new insight into macrophage phenotype transition in the regeneration of adipose tissue.

  15. A single amino acid at N-terminal region of the 2b protein of cucumber mosaic virus strain m1 has a pivotal role in virus attenuation.

    Science.gov (United States)

    Maneechoat, Phoowanarth; Takeshita, Minoru; Uenoyama, Misa; Nakatsukasa, Maki; Kuroda, Atsuko; Furuya, Naruto; Tsuchiya, Kenichi

    2015-02-02

    Host responses to infection by a mild strain of cucumber mosaic virus, termed CMV-m1, were re-examined in several plant species in comparison with those by a severe strain CMV-Y. Mild systemic symptoms were developed on the six plant species inoculated with CMV-m1. Virus titer in the Nicotiana benthamiana plants infected with CMV-m1 was significantly lower than those infected with CMV-Y, although infection by CMV-m1 interfered with further infection by CMV-Y in the plants. Subsequently, the attenuated virulence of CMV-m1 was analyzed by reassortment and recombination analyses between CMV-m1 and CMV-Y RNAs. The results suggested that the 2b protein of CMV-m1 (m1-2b) is involved in the formation of mild symptoms in N. benthamiana. Furthermore, site-directed mutagenesis demonstrated that Thr18 of m1-2b is responsible for formation of mild symptoms. Local RNA silencing suppressor activity of m1-2b was a little lower than that of severe strain CMV-Y. We discuss the relationship between attenuation of CMV-m1 and the features of m1-2b.

  16. 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...

  17. 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

  18. Determination of Virginiamycin M1 in Chinese herbs like scorpion by HPLC-MS/MS%HPLC-MS/MS法测定全蝎等动物类中药中维吉尼霉素M1

    Institute of Scientific and Technical Information of China (English)

    王少敏; 俞灵; 陈静; 郑荣; 王柯; 季申

    2011-01-01

    Objective: To establish a HPLC - MS/MS method for determination of Virginiamycin M, in Chinese Herbs made by animal such as scorpion. Methods: After being extracted by acidified 40% methanol and purified by HLB SPE column, Virginiamycin M1 was analyzed by HPLC - triple quadrupole MS. Results: There is a good linear relationship within the range of 1 ng · ml-1 ~250 ng · ml-1 for Virginiamycin M1. The regression equation is Y =3.94 ×104 X+4.07 ×103, r = 0.9996. The recovery was between 90.9% ~98.1%. The LOD in Scorpion were 0.9 μg ·kg-1. While the recovery of herbs like centipede, black snake, sea horse and leech was in the range of 85% ~95%. Conclusion:The method is sensitive, rapid, accurate and specific enough to determine Virginiamycin Ml in Scorpion.%目的:建立全蝎等动物类中药中维吉尼霉素M1的HPLC-MS/MS测定方法.方法:样品经酸化的40%甲醇提取、提取液再经过三氯甲烷萃取净化后,用高效液相色谱-三重四级杆串联质谱进行分析测定.结果:维吉尼霉素在1 ng·ml-1~250 ng·ml-1范围内与峰面积呈良好的线性关系,线形方程为Y=3.94×104X +4.07 × 103,r =0.9996,回收率在90.9-98.1%之间.在全蝎中最低检测限分别为0.7 μg·kg-1,蜈蚣、乌稍蛇、海马和水蛭等动物类药材的回收率也均在85%-95%之间.结论:本法灵敏、快速、准确、专属性强,可用于全蝎等动物类中药中维吉尼霉素M1的测定.

  19. M1, M2 Growth Scissors:Causes, Influence and Countermeasures%M1、M2月度同比增速剪刀差:成因、影响与应对

    Institute of Scientific and Technical Information of China (English)

    娄飞鹏

    2016-01-01

    Since October 2015, the monthly growth rate of M1 exceeds M2 again and continues till today, and during this period the scissors are gradually expanding. This is because monetary expansion brings more capital precipitation, but increasing liquidity doesn't effectively flow to the real economy in recent years. There are different effects of the M1 and M2 scissors on macroeconomic between long-term and short-term. To effectively cope with the M1 and M2 scissors, we need to reduce investment and financing costs and improve the efficiency of investment and financing; promote the healthy development of the real estate market and expand the main types of investment channels; flexible use of various macro-control policies, through policy coordination to improve control effect.%从2015年10月起,我国M1与M2月度同比增速剪刀差现象再次出现并延续至今,且剪刀差在逐步扩大。这次剪刀差的出现是近几年来货币扩张带来较多的资金沉淀,增加了流动性,但充裕的流动性并未有效流向实体经济所致。剪刀差的持续存在对宏观经济长短期走势存在不同的影响。为有效应对剪刀差,需要降低实体经济投融资成本,提高投融资效率;推动房地产市场健康发展,扩大各类主体的投资渠道;灵活运用各种宏观调控政策,通过政策配合提高调控效果。

  20. Determination of Virginiamycin M1in Chicken Tissues by HPLC%高效液相色谱法测定鸡组织中维吉尼亚霉素M1的残留

    Institute of Scientific and Technical Information of China (English)

    耿志明; 陈明; 许大光; 王冉; 柳伟荣; 郑勤

    2005-01-01

    鸡组织样品经甲醇- 0.2 mol/L NH4H2PO4溶液提取,正己烷洗涤,C18固相萃取柱净化后,采用高效液相色谱法测定了鸡组织中维吉尼亚霉素M1的残留量.色谱条件为二极管矩阵检测器检测;波长为245 nm;色谱柱为ODS-3C18柱(4.6 mm×250.0 mm,5.0 μm);流动相为乙腈∶水=37.5∶62.5(体积比).该方法对肌肉、肝脏和肾脏等不同鸡组织中3种维吉尼亚霉素M1浓度进行回收测定.结果表明:该方法回收率达74.5%~91.1%;批内、批间变异系数均在10%以内;最低检测限为10 ng/g.

  1. Determination of Virginiamycin M1 in Feed by Means of HPLC%高效液相色谱法测定饲料中的维吉尼亚霉素M1含量

    Institute of Scientific and Technical Information of China (English)

    耿志明; 陈明

    2005-01-01

    研究并建立了饲料中维吉尼亚霉素M1含量的高效液相色谱测定方法.样品用甲醇提取,用水稀释,经C18固相萃取柱净化,在235 nm波长下用二极管矩阵检测器检测.色谱柱:Agilent ZORBAX SBC18柱(4.6 mm×150 mm,5 μm);流动相:乙腈∶水=40∶60(体积比).维吉尼亚霉素M1质量分数在1.0~20.0 μg/ml范围内与峰面积呈良好的线性关系,回收率为91.5%~94.6%,变异系数为1.7%~3.6%.

  2. 高效液相色谱法测定猪组织中维吉尼亚霉素M1的残留%Determination of virginiamycin M1 residues in swine tissues by HPLC

    Institute of Scientific and Technical Information of China (English)

    耿志明; 陈明; 许大光; 王冉; 柳伟荣; 郑勤

    2005-01-01

    建立了猪组织中维吉尼亚霉素M1残留的高效液相色谱测定方法.样品用甲醇-0.2mol/L NH4H2PO4溶液提取,正己烷洗涤,经C18固相萃取柱净化后做HPLC分析.选用二极管矩阵检测器,波长245 nm;色谱柱为ODS-3 C18柱(4.6 mm×250mm,5 μm);流动相为乙腈-水(37.5:62.5,V/V).维吉尼亚霉素M1标准曲线线性范围在0.1~2.0 μg/mL.对不同组织的3种加药浓度进行回收率测定,回收率在72%~85%,变异系数在10%以内.最低检测限为10 ng/g.

  3. 基于IS0362-1:2007的M1类车辆轮胎噪声影响研究%The Tire Noise Research for M1 Category Based on ISO 362-1:2007

    Institute of Scientific and Technical Information of China (English)

    高吉强; 冯屹; 谢东明; 谢晋中

    2013-01-01

    Based on ISO 362-1:2007‘Measurement of noise emitted by accelerating road vehicles ’, this paper briefly elaborated its test procedure and data processing methods. Compared with the current standard, it analyzed the tire noise’s impact on noise emitted by accelerating road vehicles of M1 Category. The results show that the tire noise’s impact had increased significantly ,even became the decisive factor to the accelerating road noise and conducted a test verification.%介绍了汽车加速行驶车外噪声测量标准IS0362-1:2007的试验流程和数据处理方法,并与现行标准进行了比较。在此基础上,重点分析了新标准下轮胎噪声对M1类车辆噪声测试结果的影响,结果表明:轮胎噪声对加速噪声结果的影响有了大幅度提高,甚至成了影响试验结果的决定性因素,并对此进行了相关的试验验证。

  4. Astrocyte-Derived CCL2 is Associated with M1 Activation and Recruitment of Cultured Microglial Cells

    Directory of Open Access Journals (Sweden)

    Mingfeng He

    2016-02-01

    Full Text Available Background/Aims: Microglia are an essential player in central nervous system inflammation. Recent studies have demonstrated that the astrocytic chemokine, CCL2, is associated with microglial activation in vivo. However, CCL2-induced microglial activation has not yet been studied in vitro. The purpose of the current study was to understand the role of astrocyte-derived CCL2 in microglial activation and to elucidate the underlying mechanism(s. Methods: Primary astrocytes were pre-treated with CCL2 siRNA and stimulated with TNF-α. The culture medium (CM was collected and added to cultures of microglia, which were incubated with and without CCR2 inhibitor. Microglial cells were analyzed by quantitative RT-PCR to determine whether they polarized to the M1 or M2 state. Microglial migratory ability was assessed by transwell migration assay. Results: TNF-α stimulated the release of CCL2 from astrocytes, even if the culture media containing TNF-α was replaced with fresh media after 3 h. CM from TNF-α-stimulated astrocytes successfully induced microglial activation, which was ascertained by increased activation of M1 and enhanced migration ability. In contrast, CM from astrocytes pretreated with CCL2 siRNA showed no effect on microglial activation, compared to controls. Additionally, microglia pre-treated with RS102895, a CCR2 inhibitor, were resistant to activation by CM from TNF-α-stimulated astrocytes. Conclusion: This study demonstrates that the CCL2/CCR2 pathway of astrocyte-induced microglial activation is associated with M1 polarization and enhanced migration ability, indicating that this pathway could be a useful target to ameliorate inflammation in the central nervous system.

  5. 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.

  6. Hydroquinone induces oxidative and mitochondrial damage to human retinal Müller cells (MIO-M1).

    Science.gov (United States)

    Ramírez, Claudio; Pham, Khoa; Franco, Maria Fernanda Estragó; Chwa, Marilyn; Limb, Astrid; Kuppermann, Baruch D; Kenney, M Cristina

    2013-12-01

    Smoking is a risk factor in the development of a variety of neuroretinal diseases. Therefore, we have investigated the effects of hydroquinone (HQ), a toxicant that is present in high concentrations in cigarette smoke, on a human retinal Müller cell line (MIO-M1). MIO-M1 cells were treated for 24h with four different concentrations of HQ (200μM, 100μM, 50μM, and 25μM). Assays were used to measure cell viability, reactive oxygen/nitrogen species (ROS/RNS), mitochondrial dehydrogenase activity (WST assay), caspase-3/7 activity and lactate dehydrogenase (LDH) levels. Western blot analyses with anti-LC3 and anti-GAPDH antibodies were performed on HQ-treated samples. Some cultures were treated with 4μM rapamycin, to induce autophagy, with and without the autophagy inhibitor 3-methyl-adenine (3MA), and levels of ROS/RNS and LDH were measured. Our findings show that HQ reduced cell viability at four different concentrations tested (200, 100, 50 and 25μM); decreased mitochondrial function at concentrations of 200 and 100μM; increased ROS/RNS activity at all the concentrations tested and increased LDH levels at concentrations of 200, 100 and 50μM. Caspase-3/7 activities were not modified by HQ. However, treatment of these cells with this agent resulted in the appearance of the autophagy associated LC3-II band. Pre-treatment with 3MA reduced the ROS/RNS and LDH levels of the HQ-treated and rapamycin-treated cells. Our study suggests that HQ damages the MIO-M1 cells through oxidative, mitochondrial and autophagic pathways and not caspase-related apoptosis. Copyright © 2013 Elsevier Inc. All rights reserved.

  7. High Performance Liquid Chromatography of Propellants. Part 1. Analysis of M1, M6, and M10 Propellants

    Science.gov (United States)

    1986-05-01

    High performance liquid chromatography permits the differentation among the stabilizers and their degradation products together with accurate quantitation. This progress report describes work carried out in the analysis of single base propellants containing diphenylamine (DPA) as the stabilizer. Several degradation products have been identified and the routine determination of these compounds is feasible. The degradation of DPA seems to follow a pattern that is unique for M1 and M6’s as compared to the pattern for M10’s. It is postulated

  8. 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

  9. 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 ...... that xanomeline inhibits D-amphetamine- and (-)-apomorphine-induced behavior in Cebus apella monkeys at doses that do not cause EPS. These data further substantiate that muscarinic receptor agonists may be useful in the pharmacological treatment of psychosis....

  10. 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

    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 Pirenzepine (10 mg/h intravenously) reduced basal and vagally...... stimulated gastric and basal duodenal bicarbonate secretion by about 50% (p pirenzepine. In conclusion, human gastroduodenal mucosal bicarbonate secretion is regulated...

  11. "4M1E"法在工程安全管理中的运用

    Institute of Scientific and Technical Information of China (English)

    高新; 步晓斌

    2005-01-01

    抓住人(man)、机械(machine)、材料(material)、方法(method)、环境(enviroment)这几个主要环节实行全面质量管理,称为"4M1E"法.在施工安全管理上应用该法不但能收到较好的效果,而且使安全管理更加有序.文中以航道驳岸施工安全管理的实践加以阐述.

  12. The Effect of Spray Strips on a Model of the P3M-1 Flying Boat Hull

    Science.gov (United States)

    Dawson, John R

    1933-01-01

    This note presents the results of a series of tests made in the N.A.C.A. tank on a one-sixth full-size model of the hull and side floats of the Navy P3M-1 flying boat for the purpose of finding a method of reducing the amount of spray thrown into the propellers of this craft when taking off and landing. The model was tested without spray strips and with five different spray-strip arrangements. The best arrangement was an improvement over the bare hull with no spray strips, but the improvement was not sufficient to be satisfactory with the propellers in the designed position.

  13. Solvothermal synthesis and characterization of a novel selenidoantimonate: [M1(C4H13N3)2]n [M2Sb2Se5]n(M1- Mn、 Co, M2 = Zn、 Cd)%溶剂热法合成新型锑硒化合物[M1(C4H13N3)2]n[M2Sb2Se5]n(M1=Mn、Co,M2=Zn、Cd)及结构

    Institute of Scientific and Technical Information of China (English)

    姜浩; 王欣; 盛天录; 胡胜民; 傅瑞标; 温跃红; 沈超君; 袁宁; 吴新涛

    2011-01-01

    以二乙烯三胺为模板剂,通过溶剂热法制备了一种新型有机无机杂化锑硒化合物:[M1(C4H13N3)2]n[M2Sb2Se5]n(M1=Mn、Co,M2=Zn、Cd).相比传统的有机无机杂化锑硒化合物,过渡金属Zn和Cd参与了这种化合物主框架的构建,使化合物的主框架由传统的SbSex单元转变为Zn(Cd)SbSe5的配位单元.据我们所知,这是第一次合成出Zn和Cd参与SbSex骨架配位的有机无机杂化锑硒化合物.同时,由于结构中CdSe4和ZnSe4单元的存在,使得该化合物表现出荧光性质.这种化合物的出现,使得我们有可能通过相同的途径合成出一系列具有该类型结构特征,在发光领域有潜在应用前景的新型锑硒化合物.%A novel inorganic-organic hybrid selenidoantimonate material, [M1(C4Hi3N3)2]n[M2Sb2Se5]n (M1= Mn,Co M2= Zn, Cd), was synthesized by solvothermal reaction. Dien(diethylenetriamine) was used as a templatedirected reagent. Until now, this compound, to the best of our knowledge, is the first selenidoantimonate, in which zinc and cadmium incorporated into the SbSe3 framework, leading to the formation of ZnSbSe5 and CdSbSe5.Furthermore, because of the ZnSe4 and CdSe4 units in the framework, all the compounds exhibit emission of fluorescence. By the same way, it is possible to synthesize series of compounds with similar novel structure and potential application value in luminescence area.

  14. PICK1 confers anti-inflammatory effects in acute liver injury via suppressing M1 macrophage polarization.

    Science.gov (United States)

    Xie, Juan; Wu, Xiaoqin; Zhou, Qun; Yang, Yang; Tian, Yuanyao; Huang, Cheng; Meng, Xiaoming; Li, Jun

    2016-08-01

    Protein interacting with C kinase 1 (PICK1) is a scaffolding protein mainly implicated in neurological diseases, however, the function of PICK1 in acute liver injury (ALI) remains unknown. Our study found a dramatical decrease in mRNA and protein levels of PICK1 in liver tissues and isolated Kupffer cells (KCs) from the liver in mice with ALI. Furthermore, pretreatment the mice with ALI with FSC-231, a pharmacological inhibitor of PICK1, could significantly augment inflammatory response. Furthermore, in vitro studies showed that both lipopolysaccharide (LPS) and interferon gamma (IFN-γ) significantly reduced the expression of PICK1, while IL-4 elevated its expression in RAW 264.7 cells. Additionally, over-expression of PICK1 inhibited the expression of M1 biomarkers by suppressing NF-κB activity, and enhanced the expression of M2 biomarkers by promoting STAT6 activity. In contrast, knockdown of PICK1 or FSC-231 pretreatment promoted M1 polarization and suppressed M2 polarization. Besides, caveolin-1 was identified as a potential target gene controlled by PICK1 in RAW 264.7 cells. Mechanistic investigation revealed a dual role of PICK1 in regulating macrophage polarization and implied PICK1 as a potential therapeutic target in ALI.

  15. A rapid and versatile method to label receptor ligands using "click" chemistry: Validation with the muscarinic M1 antagonist pirenzepine.

    Science.gov (United States)

    Bonnet, Dominique; Ilien, Brigitte; Galzi, Jean-Luc; Riché, Stéphanie; Antheaune, Cyril; Hibert, Marcel

    2006-01-01

    Tagged biologically active molecules represent powerful pharmacological tools to study and characterize ligand-receptor interactions. However, the labeling of such molecules is not trivial, especially when poorly soluble tags have to be incorporated. The classical method of coupling usually necessitates a tedious final purification step to remove the excess of reagents and to isolate tagged molecules. To overcome this limitation, Cu(I)-catalyzed 1,3-dipolar cycloaddition, referred to as "click" chemistry, was evaluated as a tool to facilitate the access to labeled molecules. In order to validate the approach, we focused our attention on the incorporation of a fluorophore (Lissamine Rhodamine B), a nonfluorescent dye (Patent Blue VF), or biotin into a muscarinic antagonist scaffold derived from pirenzepine. The reaction performed in acetonitrile/water, in the presence of CuSO4 and Cu wire, allowed us to obtain three novel pirenzepine derivatives with high purity and in good yield. No coupling reagents were needed, and the quasi-stoichiometric conditions of the reaction enabled the straightforward isolation of the final product by simple precipitation and its use in bioassays. The affinity of the compounds for the human M1 muscarinic receptor fused to EGFP was checked under classical radioligand and FRET binding conditions. The three pirenzepine constructs display a nanomolar affinity for the M1 receptor. In addition, both dye-labeled derivatives behave as potent acceptors of energy from excited EGFP with a very high quenching efficiency.

  16. M1-M2 balancing act in white adipose tissue browning - a new role for RIP140.

    Science.gov (United States)

    Liu, Pu-Ste; Lin, Yi-Wei; Burton, Frank H; Wei, Li-Na

    2015-01-01

    A "Holy Grail" sought in medical treatment of obesity is to be able to biologically reprogram their adipose tissues to burn fat rather than store it. White adipose tissue (WAT) stores fuel and its expansion underlines insulin resistance (IR) whereas brown adipose tissue (BAT) burns fuel and stimulates insulin sensitivity. These two types of fats seesaw within our bodies via a regulatory mechanism that involves intricate communication between adipocytes and blood cells, particularly macrophages that migrate into adipose deposits. The coregulator, Receptor Interacting Protein 140 (RIP140), plays a key role in regulating this communication. In mice on a high-fat diet, the level of RIP140 in macrophages is dramatically elevated to activate their inflammatory M1 polarization and enhance their recruitment into WAT, facilitating IR. Conversely, lowering the level of RIP140 in macrophages not only reduces M1 macrophages but also expands alternatively polarized, anti-inflammatory M2 macrophages, triggering white adipose tissue browning, fat burning, and restoration of insulin sensitivity. This suggests a potential therapeutic strategy for reversing IR, obesity, and atherosclerotic or even cosmetic fat deposits: therapeutic browning of white adipose deposits by diminishing RIP140 levels in macrophages.

  17. 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.

  18. Preliminary study of degradation from neutron effects of core-structural materials of Thai Research Reactor TRR-1/M1

    Science.gov (United States)

    Ampornrat, P.; Boonsuwan, P.; Sangkaew, S.; Angwongtrakool, T.

    2017-06-01

    Thai research reactor went first critical in 1962. The reactor was converted in 1977 from an MTR-type with high-enriched uranium fuel to a TRIGA-MARK III type using low-enriched uranium fuel, called TRR-1/M1. Since the TRR-1/M1 has been operated for almost 40 years, degradation of reactor structural materials is expected. In this preliminary study, the potential degradation from neutron effects of core-structural materials, e.g., fuel clad (SS304) and core components (Al6061) were studied. Assessment included calculation of neutron energy, flux and fluence in the reactor core to evaluate displacement rate (dpa) and irradiation effects on the material properties. Results showed maximum displacement rates on SS304 was 5.24×10-8 per cm3·sec and on Al6061 was 1.14×10-8 per cm3·sec. The corresponding maximum displacement levels were ∼17 dpa for SS304, and ∼4 dpa for Al6061. At these levels of displacement, it is possible for the materials to result in tensile strength increasing and ductility reduction. Further inspection on the core-structural materials needs to be conducted to validate the assessment results from this study.

  19. 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.

  20. 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.

  1. Expression and functional activity of bitter taste receptors in primary renal tubular epithelial cells and M-1 cells.

    Science.gov (United States)

    Liang, Jie; Chen, Fuxue; Gu, Fu; Liu, Xin; Li, Feng; Du, Dongshu

    2017-04-01

    The kidney is essential in the maintenance of in vivo homeostasis by body fluid and electrolyte conservation and metabolic waste removal. Previously, we reported the expression of a novel G protein family (Tas2rs), which includes bitter taste receptors, in the kidney tubule system, including the nephrons and the collecting duct system. Bitter taste receptors could affect kidney function via Ca(2+) intake. Alkaloids such as phenylthiocarbamide stimulate these receptors and cause an increase in Ca(2+) intake. In this study, we determined the expression of bitter taste receptors in the immature kidney and small intestine and in primary renal epithelial cells and M-1 (collecting tubule cell line) cells, by using QPCR and immunostaining. We found no expression of bitter taste receptors in the immature kidney and small intestine several days after birth; the relative abundance of Tas2rs transcripts varied depending on the developmental stage. Tas2rs were expressed in primary renal epithelial cells and M-1 cells. The traditional Chinese medicinal plant extracts phellodendrine and coptisine caused a rapid rise in intracellular Ca(2+) concentration, which was inhibited by the phospholipase C (PLC) inhibitor U-73122. Thus, phellodendrine and coptisine could change the physiological status of renal cells in vitro by mediation of bitter taste receptors in a PLC-dependent manner. Our results provide new insights on the expression and role of bitter taste receptors in renal development and function.

  2. OPN induces FoxM1 expression and localization through ERK 1/2, AKT, and p38 signaling pathway in HEC-1A cells.

    Science.gov (United States)

    Xie, Yunpeng; Li, Yinghua; Kong, Ying

    2014-12-16

    Mammalian embryo implantation is an extremely complex process and requires endometrial receptivity. In order to establish this receptivity, sequential proliferation and differentiation during the menstrual cycle is necessary. Forkhead box M1 (FoxM1) is described as a major oncogenic transcription factor in tumor initiation, promotion and progression. According to these functions, we believe that FoxM1 should also play an essential role in embryo implantation. Osteopontin (OPN), an adhesion molecule, has been studied extensively in reproduction. In this study, we observed the expression and distribution of FoxM1 during the proliferative-phase and secretory-phase human endometrium and the pre-implantation mouse uterus firstly. Then we observed the relationship between OPN and FoxM1. Our results showed that FoxM1 was mainly distributed in glandular epithelium. OPN increased the expression of FoxM1 in the human uterine epithelial cell line HEC-1A cells in a time- and concentration-dependent manner. OPN regulates FoxM1 to influence HEC-1A cell proliferation through extracellular regulated protein kinases (ERK 1/2), protein kinase B (PKB, AKT), and the p38 mitogen activated protein kinases (p38MAPK, p38) signaling pathway. Inhibition of ERK 1/2, AKT and p38 suppressed OPN-induced FoxM1 expression and location. Our data indicate that FoxM1 might be regulated by OPN to influence endometrial proliferation to establish endometrial receptivity.

  3. 厄瓜多尔D-F油田M1油藏沉积微相研究%Research on Sedimentary Microfacies of M1 Oil Reservoir, D-F Oilfield, Ecuador

    Institute of Scientific and Technical Information of China (English)

    武凡皓

    2015-01-01

    厄瓜多尔D-F油田M1油藏目前已进入特高含水期.为了进一步提高油藏动用能力,实现井间剩余油挖潜,勘查含油富集区,通过岩心观察和测井相资料,对油藏的沉积特征及沉积模式进行分析.分析认为,该区为潮控三角洲沉积,沉积相类型分为潮汐三角洲前缘和潮汐三角洲平原亚相,也可进一步细分为潮汐河道、潮汐河道间、潮汐砂坝和内陆棚等沉积微相.

  4. 具有不耐烦顾客的M/M/1单重工作休假排队系统%The M/M/1 Queuing System with the Impatient Customers and Single Working Vacation

    Institute of Scientific and Technical Information of China (English)

    徐刚; 于泳波

    2013-01-01

    An M/M/1 queuing system with impatient customers and single working vacation was considered. When a customer arrived in the system and realized that the server was on vacation, he activated an independent ' impatient timer'. If the custmer' s service had not been completed before the customer' s timer expired, the customer abandoned the queue, without returning. Some performance measures of the system were derived such as the mean queue sizes in the busy period and in the working vacation period by balance equations and generating functions. The effects of the two service rates on the system performance measures were investigated by numerical experiment.%讨论了一个具有不耐烦顾客的M/M/1单重工作休假排队系统.工作休假期到达的顾客变得不耐烦并激活一个服从负指数分布的计时器,如果在计时器到期之前顾客没能完成服务,则该顾客离开系统,永不返回.通过平衡方程和母函数推导出正规忙期和工作休假期的平均队长等性能指标的解析表达式.通过数值算例考察了两个服务率对系统性能指标的影响.

  5. 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

  6. 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

  7. Metabolism of isothiocyanates in individuals with positive and null GSTT1 and M1 genotypes after drinking watercress juice.

    Science.gov (United States)

    Dyba, Marcin; Wang, Antai; Noone, Anne-Michelle; Goerlitz, David; Shields, Peter; Zheng, Yun-Ling; Rivlin, Richard; Chung, Fung-Lung

    2010-12-01

    Isothiocyanates (ITCs) derived from cruciferous vegetables have been shown to be promising agents against cancer in human cell culture, animal models, and in epidemiological studies. Several epidemiological studies have demonstrated an inverse relationship between intake of dietary isothiocyanates and the risk of cancers, particularly lung, colon, and breast. More importantly, the protective effects of dietary ITCs appear to be influenced by glutathione S-transferase (GST) genotype; specifically, individuals with glutathione S-transferase theta 1 (GSTT1) and glutathione S-transferase Mu 1 (GSTM1) null are better protected than those with GSTT1 and M1 positive. Although the majority of studies, especially those conducted in populations exposed to ITC rich diets, demonstrated such effects, there are a few studies that showed opposite or no association. While evidence for the interactions of dietary ITCs with GST genes is relatively strong, the reasons for the differential effects remain unclear. In this study, we examined one possible mechanism: whether subjects with null genotypes excrete ITCs at a slower rate than those with positive genotypes after drinking watercress juice, a rich source of ITCs. A total of 48 subjects, 28 GSTT1 and M1 positive and 20 null genotypes were enrolled in the study. The rates of excretion were determined using five urine samples collected over a period of 24 h after drinking watercress juice. No statistically significant differences in the rates of isothiocyanate excretion and the time of peak excretion were observed between the two tested groups having positive and null genotypes. GSTT1 and M1 genotypes are not likely to be involved in the rate of excretion of ITCs in watercress. The demonstrated differences in protection among subjects with the two genotypes are not likely due to differences in overall ITC excretion rates, however, excretion rates of ITCs other than PEITC need to be investigated. Other yet to be identified mechanism

  8. Activation of the α7 nicotinic receptor promotes lipopolysaccharide-induced conversion of M1 microglia to M2

    Science.gov (United States)

    Zhang, Qichun; Lu, Ying; Bian, Huimin; Guo, Liwei; Zhu, Huaxu

    2017-01-01

    The α7 subtype of the nicotinic acetylcholine receptor (α7 nAChR) plays an essential role in the cholinergic anti-inflammatory pathway that regulates macrophage/microglia function in inflammation. Similar to M1 and M2 macrophages, M1 and M2 microglia exhibit pro-inflammation and anti-inflammation properties, respectively. In the present study, we analyzed function-associated phenotypes to detect the transformation of microglia with activation of α7 nAChRs. We used lentivirus-mediated shRNA to knockdown the expression of α7 nAChR in BV-2 microglia incubated with lipopolysaccharides (LPS, 0.1 μg/mL) and measured the acetylcholine (Ach, 1 μg/mL)-mediated release of cytokines, such as IL-1β, IL-4, IL-6, and IL-10, in the culture supernatant via radioimmunoassay. After stimulation with Ach, the expression of typical biomarkers for different microglia phenotypes, Iba-1 and Arg-1, was determined by cellular immunofluorescence. Furthermore, the expression of signaling molecules, including p38, JAK2/STAT3, PI3K/Akt and miR-124, was analyzed via western blotting and real-time PCR. We found that Ach inhibited LPS-induced IL-1β and IL-6 elevation and promoted IL-4 and IL-10 production and that knockdown of the α7 nAChR abolished these effects of Ach. In addition, Ach decreased LPS-induced Iba-1 expression and increased Arg-1 levels in an α7 nAChR-dependent manner. The LPS-inhibited activation of JAK2/STAT3 and PI3K/Akt was also rescued by Ach, an effect that was blocked by knockdown of the α7 nAChR. In contrast, Ach triggered the phosphorylation of JAK2 and STAT3 that was otherwise inactivated by LPS in BV-2 cells. Finally, the levels of miR-124 and downstream targets C/EBPα and PU.1 were significantly enhanced in LPS-treated BV-2 microglia, and the effect of Ach on this signaling pathway was blocked by α7 nAChR knockdown as expected. Overall, our data demonstrate that activation ofα7 nAChRs inhibits the transformation of M1 microglia and promotes the M2

  9. Bacteriophage ΦM1 of Pectobacterium evolves to escape two bifunctional Type III toxin-antitoxin and abortive infection systems through mutations in a single viral gene.

    Science.gov (United States)

    Blower, Tim R; Chai, Ray; Przybilski, Rita; Chindhy, Shahzad; Fang, Xinzhe; Kidman, Samuel E; Tan, Hui; Luisi, Ben F; Fineran, Peter C; Salmond, George P C

    2017-02-03

    Some bacteria, when infected by their viral parasites (bacteriophages), undergo a suicidal response that also terminates productive viral replication (abortive infection; Abi). This response can be viewed as an altruistic act protecting the uninfected bacterial clonal population. Abortive infection can occur through the action of Type III protein-RNA toxin-antitoxin (TA) systems, such as ToxINPa from the phytopathogen, Pectobacterium atrosepticum Rare spontaneous mutants evolved in the generalized transducing phage, ΦM1, which escaped ToxINPa-mediated abortive infection in P. atrosepticum ΦM1 is a member of the Podoviridae and member of the "KMV-like viruses", a subset of the T7 supergroup. Genomic sequencing of ΦM1 escape mutants revealed single-base changes which clustered in a single open reading frame. The "escape" gene product, M1-23, was highly toxic to the host bacterium when over-expressed, but mutations in M1-23 that enabled an escape phenotype caused M1-23 to be less toxic. M1-23 is encoded within the DNA metabolism modular section of the phage genome, and when it was over-expressed, it co-purified with the host nucleotide excision repair protein, UvrA. While the M1-23 protein interacted with UvrA in co-immunoprecipitation assays, a UvrA mutant strain still aborted ΦM1, suggesting that the interaction is not critical for the Type III TA Abi activity. Additionally, ΦM1 escaped a heterologous Type III TA system (TenpINPl) from Photorhabdus luminescens (reconstituted in P. atrosepticum) through mutations in the same protein, M1-23. The mechanistic action of M1-23 is currently unknown but further analysis of this protein could provide insights into the mode of activation of both systems.

  10. Association of m1 and m2 muscarinic receptor proteins with asymmetric synapses in the primate cerebral cortex: morphological evidence for cholinergic modulation of excitatory neurotransmission.

    OpenAIRE

    Mrzljak, L; Levey, A I; Goldman-Rakic, P S

    1993-01-01

    Muscarinic m1 receptors traditionally are considered to be postsynaptic to cholinergic fibers, while m2 receptors are largely presynaptic receptors associated with axons. We have examined the distribution of these receptor proteins in the monkey cerebral cortex and obtained results that are at odds with this expectation. Using immunohistochemistry with specific antibodies to recombinant m1 and m2 muscarinic receptor proteins, we have demonstrated that both m1 and m2 receptors are prominently ...

  11. 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.

  12. Glutathione S-transferase M1 and T1 genotypes and endometriosis risk: a case-controlled study

    Institute of Scientific and Technical Information of China (English)

    林俊; 张信美; 钱羽力; 叶英辉; 石一复; 徐开红; 徐键云

    2003-01-01

    Objective To investigate the correlation between glutathione S-transferase (GST) M1 and T1 genotypes and endometriosis risk (EM). Methods Polymerase chain reaction (PCR) technique was used to detect the presence or absence of the GSTM1 and GSTT1 genes in genomic DNA isolated from the blood samples of 68 Han Chinese women with endometriosis and 28 without endometriosis. Results The frequencies of GSTM1 and GSTT1 null genotypes in women with endometriosis were 0.721 (49/68) and 0.779 (53/68), respectively, and in women without endometriosis were 0.429 (12/28) and 0.321 (9/28), respectively. There was a significant difference with regard to the frequencies of GSTM1 and GSTT1 null genotypes between the women with and without endometriosis (P0.05). Conclusion GSTM1 and GSTT1 null genotypes may be risk factors for the development of endometriosis.

  13. 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......, stereotypies and arousal as well as apomorphine-induced stereotypies and arousal in drug-naive Cebus apella monkeys. Xanomeline did not induce EPS but vomiting occurred in some monkeys at high doses, in accordance with emetic events observed in Alzheimer patients following xanomeline administration. Even when...... that xanomeline inhibits D-amphetamine- and (-)-apomorphine-induced behavior in Cebus apella monkeys at doses that do not cause EPS. These data further substantiate that muscarinic receptor agonists may be useful in the pharmacological treatment of psychosis....

  14. 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.

  15. 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.

  16. Unilateral supraorbital keyhole approach in patients with middle cerebral artery (M1-M2 segment) symmetrical aneurysms.

    Science.gov (United States)

    Martellotta, N; Gigante, N; Toscano, S; Maddalena, G F; Tripodi, M; Settembrini, G; Stroscio, C; Distefano, G; Citro, E

    2003-08-01

    A left middle cerebral artery aneurysm at the bifurcation (M1-M2 segment) and a right smaller aneurysm, symmetrical to the previous one were diagnosed in a 69-year-old female after angiographic examination for subarachnoid hemorrhage. The preoperative radiological study did not enable us to identify the bleeding aneurysm so a left supraorbital keyhole approach was performed to operate on the bigger aneurysm. In the same surgical session, using the same way of approach, we decided to attack also the right aneurysm which then revealed itself as being responsible for bleeding. The postoperative angiograms confirmed the complete exclusion of both aneurysms and the patient was discharged after good recovery. Although there are remarkable controversies about the surgical strategies for multiple aneurysms, our experience gives us the opportunity to emphasize the supraorbital keyhole approach and to reconsider the "timing" of multiple/bilateral aneurysms.

  17. Optical embedded dust sensor for engine protection and early warning on M1 Abrams/ground combat vehicles

    Science.gov (United States)

    Lin, Hai; Waldherr, Gregor A.; Burch, Timothy

    2012-06-01

    The Dual Optical Embedded Dust Sensor (DOEDS) is designed for the sensitive, accurate detection of particles for preventive health monitoring of the AGT1500 engine and M1 Abrams/Ground Combat Vehicles (GCVs). DOEDS is a real-time sensor that uses an innovative combination of optical particle sensing technologies and mechanical packaging in a rugged, compact and non-intrusive optical design. The optical sensor, implementing both a single particle sensor and a mass sensor, can operate in harsh environments (up to 400°F) to meet the particle size, size distribution, mass concentration, and response time criteria. The sensor may be flush- or inline-mounted in multiple engine locations and environments.

  18. Solubilization of matrix protein M1/M from virions occurs at different pH for orthomyxo- and paramyxoviruses.

    Science.gov (United States)

    Zhirnov, O P

    1990-05-01

    Enveloped viruses, of which the orthomyxo- and paramyxoviruses are members, are known to be uncoated by nonionic detergents in a salt concentration-dependent manner. In this study we have shown that detergent uncoating of myxoviruses depends not only on salt concentration but also on pH. Treatment of orthomyxoviruses with Nonidet-P40 or Triton N-101 at low salt concentrations results in solubilization of surface virion glycopolypeptides in alkaline and neutral pH (9.0-6.5), but in acidic pH (6.0-5.0) the viral matrix protein M1 is also removed, and the viral ribonucleoprotein complex is released. Conversely, the paramyxovirus matrix protein M is more completely solubilized in alkaline pH (pH 9.0) than in neutral and acidic pH 7.4-5.0. The described pH-dependent differences are discussed in terms of orthomyxo- and paramyxovirus uncoating in target cells.

  19. Geometries and electronic properties of Au nPd m ( n=1-4, m=-1, 0, 1) clusters

    Science.gov (United States)

    Wu, Z. J.; Zhou, S. H.; Shi, J. S.; Zhang, S. Y.

    2003-01-01

    Possible conformers for Au nPd m ( n=1-4, m=-1, 0, 1) clusters have been presented and studied by use of density functional theory. The results indicate that for n=2, linear conformer with C ∞v symmetry is the most stable for anion species, while for cation and neutral species, conformer with C 2v symmetry is the most stable. For n=3, 4, conformers with C 2v symmetry (kite-shape) are energetically favored. The calculated electron affinities (EAs) and vertical detachment energies (VDEs) are in good agreement with experiments for n=1-4. It is also interesting to note that for even n ( n=2, 4), the most stable conformers do not give the best agreement between calculated and experimental EA and VDE values, while for odd n ( n=3), the lowest energy conformer also gives the best agreement. The ionization potentials (IPs) of Au nPd clusters are calculated as well.

  20. Arginase 2 deletion leads to enhanced M1 macrophage activation and upregulated polyamine metabolism in response to Helicobacter pylori infection.

    Science.gov (United States)

    Hardbower, Dana M; Asim, Mohammad; Murray-Stewart, Tracy; Casero, Robert A; Verriere, Thomas; Lewis, Nuruddeen D; Chaturvedi, Rupesh; Piazuelo, M Blanca; Wilson, Keith T

    2016-10-01

    We reported that arginase 2 (ARG2) deletion results in increased gastritis and decreased bacterial burden during Helicobacter pylori infection in mice. Our studies implicated a potential role for inducible nitric oxide (NO) synthase (NOS2), as Arg2 (-/-) mice exhibited increased NOS2 levels in gastric macrophages, and NO can kill H. pylori. We now bred Arg2 (-/-) to Nos2 (-/-) mice, and infected them with H. pylori. Compared to wild-type mice, both Arg2 (-/-) and Arg2 (-/-) ;Nos2 (-/-) mice exhibited increased gastritis and decreased colonization, the latter indicating that the effect of ARG2 deletion on bacterial burden was not mediated by NO. While Arg2 (-/-) mice demonstrated enhanced M1 macrophage activation, Nos2 (-/-) and Arg2 (-/-) ;Nos2 (-/-) mice did not demonstrate these changes, but exhibited increased CXCL1 and CXCL2 responses. There was an increased expression of the Th1/Th17 cytokines, interferon gamma and interleukin 17, in gastric tissues and splenic T-cells from Arg2 (-/-), but not Nos2 (-/-) or Arg2 (-/-) ;Nos2 (-/-) mice. Gastric tissues from infected Arg2 (-/-) mice demonstrated increased expression of arginase 1, ornithine decarboxylase, adenosylmethionine decarboxylase 1, spermidine/spermine N (1)-acetyltransferase 1, and spermine oxidase, along with increased spermine levels. These data indicate that ARG2 deletion results in compensatory upregulation of gastric polyamine synthesis and catabolism during H. pylori infection, which may contribute to increased gastric inflammation and associated decreased bacterial load. Overall, the finding of this study is that ARG2 contributes to the immune evasion of H. pylori by restricting M1 macrophage activation and polyamine metabolism.

  1. Identification of M1 muscarinic receptors in pulmonary sympathetic nerves in the guinea-pig by use of pirenzepine.

    Science.gov (United States)

    Maclagan, J.; Fryer, A. D.; Faulkner, D.

    1989-01-01

    1. The effect of pirenzepine, a muscarinic antagonist considered to be selective for M1 receptors, was studied on bronchoconstriction and bradycardia elicited by preganglionic stimulation of the parasympathetic vagal nerves and by i.v. injections of acetylcholine (ACh) in anaesthetized guinea-pigs. 2. Pirenzepine was equipotent in the heart and lung as an antagonist of the effects of i.v. ACh at postjunctional muscarinic receptors. Doses of pirenzepine in excess of 1 mumol kg-1 abolished all muscarinic responses consistent with non-selective blockade of M3 receptors on airway smooth muscle and M2 receptors on atrial cells. 3. In the lung, low doses of pirenzepine (1-100 nmol kg-1) increased vagally-induced bronchoconstriction despite concurrent partial blockade of the postjunctional receptors. This suggests blockade of neuronal muscarinic receptors. 4. Propranolol (1 mg kg-1) increased control bronchoconstrictor responses elicited by ACh and vagal stimulation but did not alter the potency of pirenzepine for postjunctional receptors in heart or lung. However, pirenzepine-induced enhancement of vagally-induced bronchoconstriction was abolished by propranolol, suggesting that pirenzepine may be an antagonist for muscarinic receptors located in the sympathetic nerves innervating airway smooth muscle. 5. These results confirm that bronchoconstrictor stimuli indirectly initiate activation of an opposing sympathetic reflex in the guinea-pig lung. This response is facilitated by muscarinic receptors located in the sympathetic nervous pathway. 6. The high potency of pirenzepine for the neuronal receptors in the sympathetic nerves suggests that these are M1 receptors. In contrast, the parasympathetic nerves innervating airway smooth muscle in this species contain M2 receptors which inhibit neurotransmission. PMID:2758228

  2. 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.

  3. Exosome-like vesicles derived by Schistosoma japonicum adult worms mediates M1 type immune- activity of macrophage.

    Science.gov (United States)

    Wang, Lifu; Li, Zhitao; Shen, Jia; Liu, Zhen; Liang, Jinyi; Wu, Xiaoying; Sun, Xi; Wu, Zhongdao

    2015-05-01

    Exosomes are 30-100-nm membrane vesicles of endocytic origin that are released into the extracellular space upon fusion of the multi-vesicular bodies (MVB) with the plasma membrane, while initial studies described that the role of exosomes was a reticulocyte cargo-disposal mechanism allowing remodeling of the plasma membrane during the maturation of reticulocytes to erythrocytes. Recent studies indicate that exosomes are secreted by most cells and pathogens and play an important role in intercellular signaling and exert regulatory function by carrying bioactive molecules. As numerous pathogens, adult worm of Schistosoma japonicum (S. japonicum) reside in mesenteric veins of definitive host including man and mammal animals. It was reported that the worms or the eggs also have specialized secretion systems to export effector proteins or other molecules into host target cells. However, the mechanisms involved remained unclear. This study investigated the isolation of the exosome-like vesicles secreted by S. japonicum adult worms and its immune activity on microphage in vitro. In this report, we identified exosome-based secretion as a new mechanism for protein secretion by S. japonicum. Electron microscopy tomography revealed the previously unidentified ultrastructural detail of exosome-like vesicles with high resolution; they were found to be typical spherical shape and to have a diverse population that varies in size of 30-100 nm. Exosome-like vesicles isolated from S. japonicum contained a significantly different protein compared with debris pelleted and the apoptosis body. We also demonstrate that macrophages were preferentially differentiated into the M1 subtype while being treated with S. japonicum exosome-like vesicles. This study reveals there are exosome-like vesicles derived by S. japonicum adult worms, and the exosome-like vesicles can mediate M1-type immune- activity of macrophage.

  4. M/M/1/N Feedback Queue with Negative Customers and Working Vacations%带有负顾客且具有反馈的M/M/1/N工作休假排队

    Institute of Scientific and Technical Information of China (English)

    顾庆凤; 朱翼隽

    2011-01-01

    研究带反馈的且具有正、负两类顾客的M/M/1/N工作休假排队模型.工作休假策略为空竭服务多重工作休假.负顾客一对一抵消队首正在接受服务的正顾客(若有),若系统中无正顾客时,到达的负顾客自动消失,负顾客不接受服务.完成服务的正顾客以概率p(0<p≤1)离开系统,以概率1-p反馈到队尾寻求再次服务.利用马尔科夫过程理论和矩阵几何解方法求出了稳态概率的矩阵解,并得到了系统的平均队长、平均等待队长以及顾客的消失概率等性能指标.%The paper deals with an M/M/1/N feedback queue with working vacations in which customers are either "positive" or "negative" . The working vacation policy is exhaustive service and multiple working vacations. Negative customers remove positive customers only one by one at the head (if present). When a negative customer arrives, if the system is empty, it will disappear. Negative customers need no services. Just after completion of his service, a positive customer may leave the system with probability p(0 < p ≤ 1), or feedback with probability 1 - p. The matrix form solution of the steady-state probability is derived by the Markov process method and the matrix-geometric solution method. Some performance measures of the system such as the expected number of the customers in the system or in the queue and the loss probability of customer8 are also presented.

  5. The Pseudomonas syringae pv. tomato type III effector HopM1 suppresses Arabidopsis defenses independent of suppressing salicylic acid signaling and of targeting AtMIN7.

    Directory of Open Access Journals (Sweden)

    Anju Gangadharan

    Full Text Available Pseudomonas syringae pv tomato strain DC3000 (Pto delivers several effector proteins promoting virulence, including HopM1, into plant cells via type III secretion. HopM1 contributes to full virulence of Pto by inducing degradation of Arabidopsis proteins, including AtMIN7, an ADP ribosylation factor-guanine nucleotide exchange factor. Pseudomonas syringae pv phaseolicola strain NPS3121 (Pph lacks a functional HopM1 and elicits robust defenses in Arabidopsis thaliana, including accumulation of pathogenesis related 1 (PR-1 protein and deposition of callose-containing cell wall fortifications. We have examined the effects of heterologously expressed HopM1Pto on Pph-induced defenses. HopM1 suppresses Pph-induced PR-1 expression, a widely used marker for salicylic acid (SA signaling and systemic acquired resistance. Surprisingly, HopM1 reduces PR-1 expression without affecting SA accumulation and also suppresses the low levels of PR-1 expression apparent in SA-signaling deficient plants. Further, HopM1 enhances the growth of Pto in SA-signaling deficient plants. AtMIN7 contributes to Pph-induced PR-1 expression. However, HopM1 fails to degrade AtMIN7 during Pph infection and suppresses Pph-induced PR-1 expression and callose deposition in wild-type and atmin7 plants. We also show that the HopM1-mediated suppression of PR-1 expression is not observed in plants lacking the TGA transcription factor, TGA3. Our data indicate that HopM1 promotes bacterial virulence independent of suppressing SA-signaling and links TGA3, AtMIN7, and other HopM1 targets to pathways distinct from the canonical SA-signaling pathway contributing to PR-1 expression and callose deposition. Thus, efforts to understand this key effector must consider multiple targets and unexpected outputs of its action.

  6. Aflatoxin M1 in the urine of non-carriers and chronic carriers of hepatitis B virus in Maringa, Brazil

    Directory of Open Access Journals (Sweden)

    Marcel Padovani Giolo

    2012-09-01

    Full Text Available Exposure to aflatoxins (AFs in the diet may favour the development of hepatocellular carcinoma (HCC and the acute exacerbation of hepatitis in chronic hepatitis B virus (HBV carriers. Measurement of biomarkers such as aflatoxin M1 (AFM1, a metabolite of aflatoxin B1 (AFB1, in urine allows for the assessment of populations exposed to aflatoxins. The aim of this study was to investigate the occurrence of aflatoxin M1 in the urine of HBV carrier and non-carrier patients. One group included 43 randomly selected HBV carriers treated at two hospitals in the city of Maringa, Brazil, from March to June 2008. Control group consisted of 29 healthy adult volunteers with anti-HBs positive and HBsAg negative test results. Detection of AFM1 was performed by fluorescence using high performance liquid chromatography (HPLC and post-column derivation with the Kobra Cell®. Of the 72 samples analysed, 05/29 (17.2% AFM1 positive samples were from HBV non-carriers, and 16/43 (37.2% of samples were from chronic HBV carriers. This study showed AFM1 in the urine of the two surveyed population. However, there is evidence that the chronic HBV carriers have a higher risk of developing HCC due to additive interaction between AFs and HBV.A exposição às aflatoxinas (AFs na dieta é um fator de risco para o desenvolvimento do carcinoma hepatocelular (CHC e a exacerbação da hepatite aguda em indivíduos portadores do vírus da hepatite B (VHB. O uso de biomarcadores, como a aflatoxina M1 (AFM1 na urina, produto de biotransformação da aflatoxina B1 (AFB1, permite avaliar se a população está exposta às AFs. O objetivo do presente estudo foi investigar ocorrência de AFM1 na urina de portadores e não portadores crônicos do VHB. Foi selecionado um grupo, de forma aleatória, representado por 43 portadores do VHB atendidos em dois hospitais da cidade de Maringá, Brasil, no período de Março a Junho/2008. O grupo controle foi composto por 29 voluntários adultos saud

  7. FoxM1, a forkhead transcription factor is a master cell cycle regulator for mouse mature T cells but not double positive thymocytes.

    Directory of Open Access Journals (Sweden)

    Ling Xue

    Full Text Available FoxM1 is a forkhead box transcription factor and a known master regulator required for different phases of the cell cycle. In cell lines, FoxM1 deficient cells exhibit delayed S phase entry, aneuploidy, polyploidy and can't complete mitosis. In vivo, FoxM1 is expressed mostly in proliferating cells but is surprisingly also found in non-proliferating CD4(+CD8(+ double positive thymocytes. Here, we addressed the role of FoxM1 in T cell development by generating and analyzing two different lines of T-cell specific FoxM1 deficient mice. As expected, FoxM1 is required for proliferation of early thymocytes and activated mature T cells. Defective expression of many cell cycle proteins was detected, including cyclin A, cyclin B1, cdc2, cdk2, p27 and the Rb family members p107 and p130 but surprisingly not survivin. Unexpectedly, loss of FoxM1 only affects a few cell cycle proteins in CD4(+CD8(+ thymocytes and has little effect on their sensitivity to apoptosis and the subsequent steps of T cell differentiation. Thus, regulation of cell cycle genes by FoxM1 is stage- and context-dependent.

  8. 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...

  9. Bone marrow-derived and peritoneal macrophages have different inflammatory response to oxLDL and M1/M2 marker expression - implications for atherosclerosis research

    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,...

  10. 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 th...

  11. Draft genome sequence of Staphylococcus saprophyticus subsp. saprophyticus M1-1, isolated from the gills of a Korean rockfish, Sebastes schlegeli Hilgendorf, after high hydrostatic pressure processing.

    Science.gov (United States)

    Kim, Bong-Soo; Kim, Chong-Tai; Park, Bang Heon; Kwon, Sujin; Cho, Yong-Jin; Kim, Namsoo; Kim, Chul-Jin; Chun, Jongsik; Kwak, Jangyul; Maeng, Jin-Soo

    2012-08-01

    A bacterium designated M1-1 was isolated from the gills of a Korean rockfish, Sebastes schlegeli Hilgendorf, after high hydrostatic pressure processing. Studies of 16S rRNA phylogeny and comparative genomics demonstrated that the isolate belongs to Staphylococcus saprophyticus subsp. saprophyticus. Here, we report the draft genome sequence of S. saprophyticus subsp. saprophyticus M1-1 (KACC 16562).

  12. Draft Genome Sequence of Staphylococcus saprophyticus subsp. saprophyticus M1-1, Isolated from the Gills of a Korean Rockfish, Sebastes schlegeli Hilgendorf, after High Hydrostatic Pressure Processing

    OpenAIRE

    Kim, Bong-Soo; Kim, Chong-Tai; Park, Bang Heon; Kwon, Sujin; Cho, Yong-Jin; Kim, Namsoo; Kim, Chul-Jin; Chun, Jongsik; Kwak, Jangyul; Maeng, Jin-Soo

    2012-01-01

    A bacterium designated M1-1 was isolated from the gills of a Korean rockfish, Sebastes schlegeli Hilgendorf, after high hydrostatic pressure processing. Studies of 16S rRNA phylogeny and comparative genomics demonstrated that the isolate belongs to Staphylococcus saprophyticus subsp. saprophyticus. Here, we report the draft genome sequence of S. saprophyticus subsp. saprophyticus M1-1 (KACC 16562).

  13. Nostocyclopeptide-M1: a potent, nontoxic inhibitor of the hepatocyte drug transporters OATP1B3 and OATP1B1.

    Science.gov (United States)

    Herfindal, Lars; Myhren, Lene; Kleppe, Rune; Krakstad, Camilla; Selheim, Frode; Jokela, Jouni; Sivonen, Kaarina; Døskeland, Stein O

    2011-04-01

    We have isolated a novel cyanobacterial cyclic peptide (nostocyclopeptide M1; Ncp-M1) that blocks the hepatotoxic action of microcystin (MC) and nodularin (Nod). We show here that Ncp-M1 is nontoxic to primary hepatocytes in long-term culture. Ncp-M1 does not affect any known intracellular targets or pathways involved in MC action, like protein phosphatases, CaM-KII, or ROS-dependent cell death effectors. In support of this conclusion Ncp-M1 had no protective effect when microinjected into cells. Rather, the antitoxin effect was solely due to blocked hepatocyte uptake of MC and Nod. The hepatic uptake of MC and Nod is mainly via the closely related organic anion transporters OATP1B1 and OATP1B3, which also mediate hepatic transport of endogenous metabolites and hormones as well as drugs. OATP1B3 is also expressed in some aggressive cancers, where it confers apoptosis resistance. We show that Ncp-M1 inhibits transport through OATP1B3 and OATP1B1 expressed in HEK293 cells. The Ncp-M1 molecule has several nonproteinogenic amino acids and an imino bond, which hamper its synthesis. Moreover, a cyclic all L-amino acid heptapeptide analogue of Ncp-M1 also inhibits the OATP1B1/1B3 transporters, and with higher OATP1B3 preference than Ncp-M1 itself. The nontoxic Ncp-M1 and its synthetic cyclic peptide analogues thus provide new tools to probe the role of OATB1B1/1B3 mediated drug and metabolite transport in liver and cancer cells. They can also serve as scaffolds to design new, exopeptidase resistant OATP1B3-specific modulators.

  14. 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.

  15. Site-specific dephosphorylation of tau of apolipoprotein E-deficient and control mice by M1 muscarinic agonist treatment.

    Science.gov (United States)

    Genis, I; Fisher, A; Michaelson, D M

    1999-01-01

    Apolipoprotein E (apoE)-deficient mice have memory deficits that are associated with synaptic loss of basal forebrain cholinergic projections and with hyperphosphorylation of distinct epitopes of the microtubule-associated protein tau. Furthermore, treatment of apoE-deficient mice with the M1 selective agonist 1-methylpiperidine-4-spiro-(2'-methylthiazoline) [AF150(S)] abolishes their memory deficits and results in recovery of their brain cholinergic markers. In the present study, we used a panel of anti-tau monoclonal antibodies to further map the tau epitopes that are hyperphosphorylated in apoE-deficient mice and examined the effects of prolonged treatment with AF150(S). This revealed that tau of apoE-deficient mice contains a distinct, hyperphosphorylated "hot spot" domain which is localized N-terminally to the microtubule binding domain of tau, and that AF150(S) has an epitope-specific tau dephosphorylating effect whose magnitude is affected by apoE deficiency. Accordingly, epitopes which reside in the hyperphosphorylated "hot spot" are dephosphorylated by AF150(S) in apoE-deficient mice but are almost unaffected in the controls, whereas epitopes which flank this tau domain are dephosphorylated by AF150(S) in both mice groups. In contrast, epitopes located at the N and C terminals of tau are unaffected by AF150(S) in both groups of mice. These findings suggest that apoE deficiency results in hyperphosphorylation of a distinct tau domain whose excess phosphorylation can be reduced by muscarinic treatment.

  16. 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.

  17. 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.

  18. Direct observation of the M1 transition between the ground state fine structure splitting of W VIII

    CERN Document Server

    Mita, Momoe; Kato, Daiji; Murakami, Izumi; Nakamura, Nobuyuki

    2016-01-01

    We present direct observation of the M1 transition between the fine structure splitting in the 4f13 5s2 5p6 2F ground state 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 lack. 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 the identification of the previously-unreported visible lines. The observed wavelength 574.47 pm 0.03 nm (air), which corresponds to the fine structure splitting of 17402.5 pm 0.9 cm-1, shows reasonable agreement with the previously reported value 17410 pm 5 cm-1 obtained indirectly through the analysis of EUV spectra [Ryabtsev et al., Atoms 3 (2015) 273].

  19. Aflatoxin M1 Concentration in Various Dairy Products: Evidence for Biologically Reduced Amount of AFM1 in Yoghurt.

    Science.gov (United States)

    Rahimirad, Amir; Maalekinejad, Hassan; Ostadi, Araz; Yeganeh, Samal; Fahimi, Samira

    2014-08-01

    Aflatoxin M1 (AFM1), a carcinogenic substance is found in milk and dairy products. The effect of season and type of dairy products on AFMi level in northern Iran was investigated in this study. Three hundred samples (each season 75 samples) including raw and pasteurized milk, yoghurt, cheese, and cream samples were collected from three distinct milk producing farms. The samples were subjected to chemical and solid phase extractions and were analyzed by using HPLC technique. Recovery percentages, limit of detection and limit of quantification values were determined. Seventy percent and 98% were the minimum and maximum recoveries for cheese and raw milk, respectively and 0.021 and 0.063 ppb were the limit of detection and limit of quantification values for AFM1. We found that in autumn and winter the highest level (0.121 ppb) of AFM1 in cheese and cream samples and failed to detect any AFM1 in spring samples. Interestingly, our data showed that the yoghurt samples had the lowest level of AFM1 in all seasons. There are significant differences between the AFM1 levels in dairy products in various seasons and also various types of products, suggesting spring and summer yoghurt samples as the safest products from AFM1 level point of view.

  20. Determination of aflatoxin M1 in breast milk as a biomarker of maternal and infant exposure in Colombia.

    Science.gov (United States)

    Diaz, Gonzalo J; Sánchez, Marlib Paloma

    2015-01-01

    Chronic exposure to aflatoxins, and especially to aflatoxin B1 (AFB1), causes hepatocellular carcinoma with prevalence 16-32 times higher in developing compared with developed countries. Aflatoxin M1 (AFM1) is a monohydroxylated metabolite from AFB1 that is secreted in milk and which can be used as a biomarker of AFB1 exposure. This study aimed to determine AFM1 levels in human breast milk using immunoaffinity column clean-up with HPLC and fluorescence detection. Breast milk samples were obtained from 50 nursing mothers. Volunteers filled in a questionnaire giving their consent to analyse their samples as well as details of their socioeconomic, demographic and clinical data. The possible dietary sources of aflatoxins were assessed using a food frequency questionnaire. A total of 90% of the samples tested positive for AFM1, with a mean of 5.2 ng l(-1) and a range of 0.9-18.5 ng l(-1). The study demonstrated a high frequency of exposure of mothers and neonates to AFB1 and AFM1 in Colombia, and it points out the need to regulate and monitor continuously the presence of aflatoxins in human foods. Further research is needed in order to determine the presence of other mycotoxins in foods and in human samples as well as to devise protection strategies in a country where mycotoxins in human foods are commonly found.

  1. STUDY OF THE DELETION MUTATION OF GLUTATHIONE S TRANSFERASE M1 GENE AND ITS ROLE IN SUSCEPTIBILITY TO HEPATOCELLULAR CARCINOMA

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objection: To investigate the glutathione S transferase M1 (GSTM1) gene inherent deletion and its relation to prevalence of hepatocellular carcinoma (HCC) in Guangxi, China. Methods: The GSTM1 gene polymorphism of 120 HCC patients and 100 healthy subjects both from the same high aflatoxin B1 (AFB1) contaminated area were detected using PCR technique with special primers. Another 40 patients from AFB1 low risk area were also tested. Results: In HCC high risk area, it was found that the frequencies of GSTM1 null genotype in HCC patients and healthy subjects were 59% and 51% respectively, with no significant difference. However, the frequency of GSTM1-null genotype in control group from AFB1 low risk area was lower than those from high risk area (P<0.01). Conclusion: Populations in this HCC endemic region show a higher rate of GSTM1-null genotype, which may be partially responsible for the susceptibility to AFB1 induced HCC. But the detoxification effect of GSTM1 alone is not sufficient to resist the genetic toxicity of AFB1, especially in those people who expose to excess AFB1. The GSTM1 gene deletion would not be suitable as an independent predictor of susceptibility to HCC.

  2. NEW ORBITS FOR COMETS C/1960 M1 (HUMASON, C/1980 E1 (BOWELL, AND MUSINGS ON EXTRASOLAR COMETS

    Directory of Open Access Journals (Sweden)

    Richard L. Branham Jr.

    2013-01-01

    Full Text Available Se calculan órbitas nuevas para los cometas Humason (C/1960 M1 y Bowell (C/1980 E1. La órbita de Humason se basa en 34 observaciones hechas durante 348 días y para Bowell en 203 observaciones hechas durante ocho años. Integraciones hacia atrás indican que ambos cometas tenían órbitas originalmente muy elípticas, que fueron cambiadas a hipérbolas por la adición de energía desde el Sistema Solar. Puesto que sus distancias del perihelio son mayores de 3 AU, la posibilidad de fuerzas no gravitatorias es remota. Para el cometa Secchi (C/1853 E1, sin embargo, la órbita es hiperbólica a una distancia de más de 100000 AU del Sol y sin evidencia alguna de fuerzas no gravitatorias. Si la órbita permanece hiperbólica a esa distancia, quizás su origen sea fuera de la nube de Oort.

  3. Antibody against recombinant heat labile enterotoxin B subunit (rLTB could block LT binding to ganglioside M1 receptor

    Directory of Open Access Journals (Sweden)

    SM Moazzeni

    2010-12-01

    Full Text Available Objectives: Enterotoxigenic Escherichia coli (ETEC is one of the most common agents of diarrhea among other bacterial agents. Designing and producing vaccine against these bacteria is one of the major purposes of World Health Organization (WHO. Due to presence of diverse clones of ETEC strains in the world, the use of global vaccines for ETEC infection is controversial. B subunit of heat labile toxin (LTB was introduced as a vaccine candidate molecule by several investigators. The expression of LTB gene isolated from a local bacterial strain and investigation of its immunological property was the objective of this study."nMaterials and Methods: LTB gene was isolated from a local isolated ETEC, cloned and expressed using pET28a expression vector. For LTB gene expression, the three main expression parameters (IPTG concentration, time and temperature of induction were investigated. The recombinant protein was purified ( > 95% with Ni-NTA column using 6XHis-tag and used as an antigen in ELISA test."nResults: The immunological analyses showed production of high titer of specific antibody in immunized mice. Anti LTB Antibody could bind to whole toxin and neutralize the toxin through inhibition of its binding to the Ganglioside M1 receptor."nConclusion: The recombinant LTB protein is a highly immunogenic molecule. Considering the LTB role in ETEC pathogenesis, it can be taken into account as one of the most important components of vaccines against local ETEC.

  4. STUDIES ON MUTAGENIC EFFECTS OF GAMMA RAYS AND ETHYL METHYL SULFONATE ON M 1 GENERATION IN ADT 47 RICE

    Directory of Open Access Journals (Sweden)

    D.RAJARAJAN 1 , R.SARASWATHI 2 , D. SASSIKUMAR 3 AND S.K GANESH 4

    2015-01-01

    Full Text Available ABSTRACT: A study was conducted to assess the effects of physical mutagen gamma rays and  a  chemical  mutagen  EMS  on  rice  cultivar  ADT  (R  47  to  study  the morphological  variations  in  this  variety.  For  inducing  macro  and  micro mutations, the dose applied were 200Gy, 250Gy and 300Gy of gamma rays and 100mM,  120mM  and  140mM  of  EMS.  In  initial  evaluation  trial  (M 1 ,  the germination percentage, seedlings survival percentage, plant height on 30 th  day, pollen fertility, plant height at maturity, seed fertility showed a dose dependent reduction for both the mutagens. Among the various traits, seedling height on 30 th  day and the plant height at maturity exhibited less variation between the mutagens. KEY WORDS: Mutagenic effects, Gamma Rays, 47 Rice.

  5. 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

    2015-12-01

    Epithelial ovarian cancer (EOC) is the leading cause of death from gynecologic malignancy, with high mortality attributable to widespread intraperitoneal 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 mesomimetic 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 intraperitoneal tumor burden was observed in overweight or obese animals in three distinct in vivo models. Further histologic 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 affects ovarian cancer metastatic success, which likely contributes to the negative correlation between obesity and ovarian cancer survival. ©2015 American Association for Cancer Research.

  6. Direct and ultrasensitive optofluidic-based immunosensing assay of aflatoxin M1 in dairy products using organic solvent extraction.

    Science.gov (United States)

    Lou, Xuening; Zhu, Anna; Wang, Hongliang; Wu, Jun; Zhou, Liping; Long, Feng

    2016-10-12

    Aflatoxin M1 (AFM1), a highly toxic secondary metabolite, is present in a wide range of dairy products. In this study, we designed a simple, low-cost, reusable, and easy-to-operate immunosensing method for ultrasensitive detection of AFM1 in dairy products by using a portable evanescent wave-based optofluidic biosensing platform (EOBP). The developed method provides the minimum detection limit of 5 ng/L, which is below the most restrictive standard imposed by the current regulations for AFM1 in dairy products. The effect of several organic solvents, such as methanol, acetone, and acetonitrile, on the binding reaction of antibody-antigen in heterogeneous and homogeneous solutions was evaluated. Although the effect of organic solvents on the homogeneous binding reaction between antibody and antigen is more significant than that of heterogeneous binding reaction between antibody in solution and antigen immobilized onto the sensor surface, the fluorescence signal detected by EOBP is linearly dependent on AFM1 concentration. Therefore, AFM1 can be directly quantified even if the samples contain a certain organic solvent concentration. The robustness and stability of AFM1-ovalbumin conjugate allow the regeneration of modified biosensor surface for more than 200 times, thereby achieving a cost-effective and reliable AFM1 determination. The proposed method provides a rapid, ultrasensitive, and reliable AFM1 determination in dairy products without complicated sample pretreatment process.

  7. Glutathione-S-transferases M1/T1 gene polymorphisms and endometriosis: a meta-analysis in Chinese populations.

    Science.gov (United States)

    Chen, Xin-Ping; Xu, Da-Feng; Xu, Wei-Hua; Yao, Jia; Fu, Sheng-Miao

    2015-01-01

    In view of the controversies surrounding the glutathione-S-transferases (GST) M1/T1-endometriosis association, a meta-analysis of the GSTM1/GSTT1 genetic association studies of endometriosis was performed in Chinese populations. PubMed, Springer Link, OvidSP, and Chinese databases were searched for related studies. A total of nine studies on GSTM1-endometriosis involved 874 cases and 997 controls, and five studies on GSTT1 involved 404 cases and 513 controls were included in this meta-analysis. Overall, the null genotype of GSTM1/GSTT1 was significantly related to endometriosis risk in Chinese populations (GSTM1, OR = 2.21, 95% CI: 1.22-4.01; GSTT1, OR = 2.31, 95% CI: 1.34-3.99). In subgroup analyses stratified by ethnicity and source of controls, the same results were observed in Chinese Han and population-based studies. The sensitivity analysis confirmed the reliability and stability of the meta-analysis. No publication bias was found among studies by Egger's test. In conclusion, our meta-analysis supports that the GSTM1/GSTT1 null genotype might contribute to individual susceptibility to endometriosis in Chinese populations, especially in Chinese Han.

  8. A scheme for radiation pressure and photon diffusion with the M1 closure in RAMSES-RT

    Science.gov (United States)

    Rosdahl, J.; Teyssier, R.

    2015-06-01

    We describe and test an updated version of radiation-hydrodynamics in the RAMSES code, that includes three new features: (i) radiation pressure on gas, (ii) accurate treatment of radiation diffusion in an unresolved optically thick medium, and (iii) relativistic corrections that account for Doppler effects and work done by the radiation to first order in v/c. We validate the implementation in a series of tests, which include a morphological assessment of the M1 closure for the Eddington tensor in an astronomically relevant setting, dust absorption in an optically semithick medium, direct pressure on gas from ionizing radiation, convergence of our radiation diffusion scheme towards resolved optical depths, correct diffusion of a radiation flash and a constant luminosity radiation, and finally, an experiment from Davis et al. of the competition between gravity and radiation pressure in a dusty atmosphere, and the formation of radiative Rayleigh-Taylor instabilities. With the new features, RAMSES-RT can be used for state-of-the-art simulations of radiation feedback from first principles, on galactic and cosmological scales, including not only direct radiation pressure from ionizing photons, but also indirect pressure via dust from multiscattered IR photons reprocessed from higher-energy radiation, both in the optically thin and thick limits.

  9. A scheme for radiation pressure and photon diffusion with the M1 closure in RAMSES-RT

    CERN Document Server

    Rosdahl, J

    2014-01-01

    We describe and test an updated version of radiation-hydrodynamics (RHD) in the RAMSES code, that includes three new features: i) radiation pressure on gas, ii) accurate treatment of radiation diffusion in an unresolved optically thick medium, and iii) relativistic corrections that account for Doppler effects and work done by the radiation to first order in v/c. We validate the implementation in a series of tests, which include a morphological assessment of the M1 closure for the Eddington tensor in an astronomically relevant setting, dust absorption in a optically semi-thick medium, direct pressure on gas from ionising radiation, convergence of our radiation diffusion scheme towards resolved optical depths, correct diffusion of a radiation flash and a constant luminosity radiation, and finally, an experiment from Davis et al. of the competition between gravity and radiation pressure in a dusty atmosphere, and the formation of radiative Rayleigh-Taylor instabilities. With the new features, RAMSES-RT can be us...

  10. Aflatoxin M1 cytotoxicity against human intestinal Caco-2 cells is enhanced in the presence of other mycotoxins.

    Science.gov (United States)

    Gao, Y N; Wang, J Q; Li, S L; Zhang, Y D; Zheng, N

    2016-10-01

    Aflatoxin M1 (AFM1), a class 2B human carcinogen, is the only mycotoxin with established maximum residue limits (MRLs) in milk. Toxicological data for other mycotoxins in baby food, containing cereals and milk, either in isolation or in combination with AFM1, are sparse. The aim of this study was to investigate the cytotoxicity of AFM1, ochratoxin A (OTA), zearalenone (ZEA), and α-zearalenol (α-ZOL), individually and in combinations, in human Caco-2 cells. The tetrazolium salt (MTT) assay demonstrated that (i) OTA and AFM1 had similar cytotoxicity, which was higher than that of ZEA and α-ZOL, after a 72 h exposure; and (ii) the quaternary combination had the highest cytotoxicity, followed by tertiary and binary combinations and individual mycotoxins. Isobologram analysis indicated that the presence of OTA, ZEA, and/or α-ZOL with AFM1 led to additive and synergistic cytotoxicity in most combinations. The cytotoxicity of OTA was similar to that of AFM1, suggesting that OTA in food poses a health risk to consumers. Furthermore, AFM1 cytotoxicity increased dramatically in the presence of OTA, ZEA, and/or α-ZOL (p mycotoxins in baby food which contains milk and cereals.

  11. Herschel observations of the nebula M1-67 around the Wolf-Rayet star WR 124

    CERN Document Server

    Vamvatira-Nakou, C; Royer, P; Waelkens, C; Groenewegen, M A T; Barlow, M J

    2016-01-01

    Infrared Herschel imaging and spectroscopic observations of the nebula M1-67 around the Wolf-Rayet star WR 124 have been obtained along with optical imaging observations. The infrared images reveal a clumpy dusty nebula that extends up to 1 pc. The comparison with the optical images shows that the ionized gas nebula coincides with the dust nebula, the dust and the gas being mixed together. A photodissociation region is revealed from the infrared spectroscopic analysis. The analysis of the infrared spectrum of the nebula, where forbidden emission lines of ionized elements were detected, showed that the nebula consists of mildly processed material with the calculated abundance number ratios being N/O = 1.0 +/- 0.5 and C/O = 0.46 +/- 0.27. Based on a radiative transfer model, the dust mass of the nebula was estimated to be 0.22 Msun with a population of large grains being necessary to reproduce the observations. The comparison of the mass-loss rate and the abundance ratios to theoretical models of stellar evolut...

  12. Geometry and stability of BenCm (n=1-10; m=1, 2, ..., to 11-n) clusters.

    Science.gov (United States)

    Ghouri, Mohammed M; Yareeda, Lakshmi; Mainardi, Daniela S

    2007-12-20

    Density functional theory B3PW91/6-31+G* calculations on BenCm (n=1-10; m=1, 2, ..., to 11-n) clusters have been carried out to examine the effect of cluster size, relative composition, binding energy per atom, HOMO-LUMO gap, vertical ionization potential, and electron affinity on their relative stabilities. The most stable planar cyclic conformations of these clusters always show at least a set of two carbon atoms between two beryllium atoms, while structures where beryllium atoms cluster together, or allow the intercalation of one carbon atom between two of them, generally seem to be the least stable ones. Clusters containing 1, 2, and 3 beryllium atoms (Be2C8, Be3C6, Be2C6, BeC6, Be2C4, BeC4, Be2C2, and BeC2) are identified as clusters of "magic numbers" in terms of their high binding energy per atom, high HOMO-LUMO gap, vertical ionization potential, and second difference in energy per beryllium atom.

  13. Sensitive and rapid detection of aflatoxin M1 in milk utilizing enhanced SPR and p(HEMA) brushes.

    Science.gov (United States)

    Karczmarczyk, Aleksandra; Dubiak-Szepietowska, Monika; Vorobii, Mariia; Rodriguez-Emmenegger, Cesar; Dostálek, Jakub; Feller, Karl-Heinz

    2016-07-15

    The rapid and sensitive detection of aflatoxin M1 (AFM1) in milk by using surface plasmon resonance (SPR) biosensor is reported. This low molecular weight mycotoxin is analyzed using an indirect competitive immunoassay that is amplified by secondary antibodies conjugated with Au nanoparticles. In order to prevent fouling on the sensor surface by the constituents present in analyzed milk samples, an interface with poly(2-hydroxyethyl methacrylate) p(HEMA) brush was employed. The study presents a comparison of performance characteristics of p(HEMA)-based sensor with a regularly used polyethylene glycol-based architecture relying on mixed thiol self-assembled monolayer. Both sensors are characterized in terms of surface mass density of immobilized AFM1 conjugate as well as affinity bound primary and secondary antibodies. The efficiency of the amplification strategy based on Au nanoparticle is discussed. The biosensor allowed for highly sensitive detection of AFM1 in milk with a limit of detection (LOD) as low as 18pgmL(-1) with the analysis time of 55min.

  14. Design and Optimization of SiON Ring Resonator-Based Biosensors for Aflatoxin M1 Detection

    Directory of Open Access Journals (Sweden)

    Romain Guider

    2015-07-01

    Full Text Available In this article, we designed and studied silicon oxynitride (SiON microring-based photonic structures for biosensing applications. We designed waveguides, directional couplers, and racetrack resonators in order to measure refractive index changes smaller than 10−6 refractive index units (RIU. We tested various samples with different SiON refractive indexes as well as the waveguide dimensions for selecting the sensor with the best performance. Propagation losses and bending losses have been measured on test structures, along with a complete characterization of the resonator’s performances. Sensitivities and limit of detection (LOD were also measured using glucose-water solutions and compared with expected results from simulations. Finally, we functionalized the resonator and performed sensing experiments with Aflatoxin M1 (AFM1. We were able to detect the binding of aflatoxin for concentrations as low as 12.5 nm. The results open up the path for designing cost-effective biosensors for a fast and reliable sensitive analysis of AFM1 in milk.

  15. Column number density expressions through M = 0 and M = 1 point source plumes along any straight path

    Science.gov (United States)

    Woronowicz, Michael

    2016-11-01

    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.

  16. 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.

  17. Photoelectron spectroscopy and density functional calculations of C(n)S(m)(-) (n = 2-7; m = 1, 2) clusters.

    Science.gov (United States)

    Xu, Xi-Ling; Deng, Xiao-Jiao; Xu, Hong-Guang; Zheng, Wei-Jun

    2015-12-14

    CnSm(-) (n = 2-7; m = 1, 2) clusters were investigated by using photoelectron spectroscopy combined with density functional theory calculations. We found that the vertical detachment energies of both CnS(-) and CnS2(-) (n = 2-7) clusters exhibit a strong odd-even alternation with an increasing number of carbon atoms: the VDEs of even-n clusters are higher than those of adjacent odd-n clusters. The most stable structures of the anionic and neutral CnS (n = 2-7) clusters are linear with the S atom locating at one end of the carbon chain except that the structure of C3S(-) is slightly bent. The ground state isomers of the anionic and neutral CnS2 (n = 2-7) clusters are all linear structures with two S atoms locating at two ends of the carbon chain. The electron affinities of the neutral CnS (n = 2, 4-7) and CnS2 (n = 2-7) clusters are determined based on the experimental adiabatic detachment energies of the corresponding anion species, because the most stable structures of the neutral clusters are similar to those of the corresponding anions.

  18. Mathematical Model for the Optimal Utilization Percentile in M/M/1 Systems: A Contribution about Knees in Performance Curves

    CERN Document Server

    Gonzalez-Horta, Francisco A; Ramirez-Cortes, Juan M; Martinez-Carballido, Jorge; Buenfil-Alpuche, Eldamira

    2011-01-01

    Performance curves of queueing systems can be analyzed by separating them into three regions: the flat region, the knee region, and the exponential region. Practical considerations, usually locate the knee region between 70-90% of the theoretical maximum utilization. However, there is not a clear agreement about where the boundaries between regions are, and where exactly the utilization knee is located. An open debate about knees in performance curves was undertaken at least 20 years ago. This historical debate is mainly divided between those who claim that a knee in the curve is not a well defined term in mathematics, or it is a subjective and not really meaningful concept, and those who define knees mathematically and consider their relevance and application. In this paper, we present a mathematical model and analysis for identifying the three mentioned regions on performance curves for M/M/1 systems; specifically, we found the knees, or optimal utilization percentiles, at the vertices of the hyperbolas tha...

  19. Column Number Density Expressions Through M = 0 and M = 1 Point Source Plumes Along Any Straight Path

    Science.gov (United States)

    Woronowicz, Michael S.

    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 plumes axis. For sonic plumes this ratio is reduced to about 43. For high Mach number cases the maximum CND will be found along the axial centerline path.

  20. Nuclear track-etched pore membrane production using neutrons from the Thai research reactor TRR-1/M1

    Directory of Open Access Journals (Sweden)

    Thawat Chittrakarn

    2002-11-01

    Full Text Available This work presents the results of the nuclear pore membrane production using the neutrons from the Thai research reactor TRR-1/M1 for pore piercing process on the polycarbonate thin film. With our experimental design, the fast neutron provides better results in pore piercing comparing with thermal neutron bombardment. This can be explained by most of the latent tracks produced by thermal neutron bombardment not penetrating through the thin film. Chemical etching process using NaOH solution with appropriate time, concentration and temperature is employed to enlarge the latent tracks in the bombarded film. Fast neutron bombardment with 5, 10 and 20 minutes bombarding time successfully produces the nuclear track membrane. Pore size and pore density of the produced membranes examined by SEM are 0.24 – 1.01 μm and 4.7 – 245 × 106 pore/cm2, respectively. Bubble point tests show the maximum pore diameter of the produced membrane ranged between 1.18 – 3.25 μm.

  1. Pharmacologic or Genetic Targeting of Glutamine Synthetase Skews Macrophages toward an M1-like Phenotype and Inhibits Tumor Metastasis

    Directory of Open Access Journals (Sweden)

    Erika M. Palmieri

    2017-08-01

    Full Text Available Glutamine-synthetase (GS, the glutamine-synthesizing enzyme from glutamate, controls important events, including the release of inflammatory mediators, mammalian target of rapamycin (mTOR activation, and autophagy. However, its role in macrophages remains elusive. We report that pharmacologic inhibition of GS skews M2-polarized macrophages toward the M1-like phenotype, characterized by reduced intracellular glutamine and increased succinate with enhanced glucose flux through glycolysis, which could be partly related to HIF1α activation. As a result of these metabolic changes and HIF1α accumulation, GS-inhibited macrophages display an increased capacity to induce T cell recruitment, reduced T cell suppressive potential, and an impaired ability to foster endothelial cell branching or cancer cell motility. Genetic deletion of macrophagic GS in tumor-bearing mice promotes tumor vessel pruning, vascular normalization, accumulation of cytotoxic T cells, and metastasis inhibition. These data identify GS activity as mediator of the proangiogenic, immunosuppressive, and pro-metastatic function of M2-like macrophages and highlight the possibility of targeting this enzyme in the treatment of cancer metastasis.

  2. Recombinant human interleukin-1 receptor antagonist promotes M1 microglia biased cytokines and chemokines following human traumatic brain injury.

    Science.gov (United States)

    Helmy, Adel; Guilfoyle, Mathew R; Carpenter, Keri Lh; Pickard, John D; Menon, David K; Hutchinson, Peter J

    2016-08-01

    Interleukin-1 receptor antagonist (IL1ra) has demonstrated efficacy in a wide range of animal models of neuronal injury. We have previously published a randomised controlled study of IL1ra in human severe TBI, with concomitant microdialysis and plasma sampling of 42 cytokines and chemokines. In this study, we have used partial least squares discriminant analysis to model the effects of drug administration and time following injury on the cytokine milieu within the injured brain. We demonstrate that treatment with rhIL1ra causes a brain-specific modification of the cytokine and chemokine response to injury, particularly in samples from the first 48 h following injury. The magnitude of this response is dependent on the concentration of IL1ra achieved in the brain extracellular space. Chemokines related to recruitment of macrophages from the plasma compartment (MCP-1) and biasing towards a M1 microglial phenotype (GM-CSF, IL1) are increased in patient samples in the rhIL1ra-treated patients. In control patients, cytokines and chemokines biased to a M2 microglia phenotype (IL4, IL10, MDC) are relatively increased. This pattern of response suggests that a simple classification of IL1ra as an 'anti-inflammatory' cytokine may not be appropriate and highlights the importance of the microglial response to injury.

  3. Identification of limit and determination of aflatoxin-M1 in milk and dairy products%乳与乳制品中黄曲霉毒素M1的限量确定及测定方法

    Institute of Scientific and Technical Information of China (English)

    张宗城

    2010-01-01

    @@ 黄曲霉毒素是毒性最大的真菌毒素.产生黄曲霉毒素B1(AFB1)的霉菌主要有两种,即黄曲霉菌(Aspergillus flavus)、寄生曲霉菌(Aspergillus parasiticus).另外还有Aspergillus nomius中的个别菌株.黄曲霉毒素M1(AFM1)是AFB1的4-羟基衍生物,分子式C17H12O7,分子量328.乳与乳制品中的黄曲霉毒素AFM1与乳畜的饲料有关,与乳与乳制品生产加工基本无关,在乳畜体内由饲料的AFB1转化而来进入乳汁.AFB1和AFM1是致癌致畸致突变的毒物,危害部位主要是肝脏[1],同时具有免疫毒性,降低免疫能力[2],降低动物生产性能[3].进入20世纪以来关于黄曲霉毒素的立法限量与毒理的深入研究同步,但对AFM1的研究进程和立法的国家尚不如AFB1.

  4. FoxM1 Drives a Feed-forward STAT3-activation Signaling Loop that Promotes the Self-renewal and Tumorigenicity of Glioblastoma Stem-like Cells

    Science.gov (United States)

    Gong, Ai-hua; Wei, Ping; Zhang, Sicong; Yao, Jun; Yuan, Ying; Zhou, Ai-dong; Lang, Frederick F.; Heimberger, Amy B.; Rao, Ganesh; Huang, Suyun

    2015-01-01

    The growth factor PDGF controls the development of glioblastoma (GBM) but its contribution to the function of GBM stem-like cells (GSC) has been little studied. Here we report that the transcription factor FoxM1 promotes PDGFA-STAT3 signaling to drive GSC self-renewal and tumorigenicity. In GBM we found a positive correlation between expression of FoxM1 and PDGF-A. In GSC and mouse neural stem cells, FoxM1 bound to the PDGF-A promoter to upregulate PDGF-A expression, acting to maintain the stem-like qualities of GSC in part through this mechanism. Analysis of the human cancer genomic database TCGA revealed that GBM express higher levels of STAT3, a PDGF-A effector signaling molecule, as compared with normal brain. FoxM1 regulated STAT3 transcription through interactions with the β-catenin/TCF4 complex. FoxM1 deficiency inhibited PDGF-A and STAT3 expression in neural stem cells and GSC, abolishing their stem-like and tumorigenic properties. Further mechanistic investigations defined a FoxM1-PDGFA-STAT3 feed-forward pathway that was sufficient to confer stem-like properties to glioma cells. Collectively, our findings showed how FoxM1 activates expression of PDGF-A and STAT3 in a pathway required to maintain the self-renewal and tumorigenicity of glioma stem-like cells. PMID:25832656

  5. Snailase Preparation of Ginsenoside M1 from Protopanaxadiol-Type Ginsenoside and Their Protective Effects Against CCl4-Induced Chronic Hepatotoxicity in Mice

    Directory of Open Access Journals (Sweden)

    Li Chen

    2011-12-01

    Full Text Available To investigate the protective effects of protopanaxadiol-type ginsenoside (PDG and its metabolite ginsenoside M1 (G-M1 on carbon tetrachloride (CCl4-induced chronic liver injury in ICR mice, we carried out conversion of protopanaxadiol-type ginsenosides to ginsenoside M1 using snailase. The optimum time for the conversion was 24 h at a constant pH of 4.5 and an optimum temperature of 50 °C. The transformation products were identified by high-performance liquid chromatography and electrospray ion-mass spectrometry. Subsequently, most of PDG was decomposed and converted into G-M1 by 24 h post-reaction. During the study on hepatoprotective in a mice model of chronic liver injury, PDG or G-M1 supplement significantly ameliorated the CCl4-induced liver lesions, lowered the serum levels of select hepatic enzyme markers (alanine aminotransferase, ALT, and aspartate aminotransferase, AST and malondialdehyde and increased the activity of superoxide dismutase in liver. Histopathology of the liver tissues showed that PDG and G-M1 attenuated the hepatocellular necrosis and led to reduction of inflammatory cell infiltration. Therefore, the results of this study show that PDG and G-M1 can be proposed to protect the liver against CCl4-induced oxidative injury in mice, and the hepatoprotective effect might be attributed to amelioration of oxidative stress.

  6. 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.

  7. Occurrence of aflatoxin M1 in human milk samples in Vojvodina, Serbia: Estimation of average daily intake by babies.

    Science.gov (United States)

    Radonić, Jelena R; Kocić Tanackov, Sunčica D; Mihajlović, Ivana J; Grujić, Zorica S; Vojinović Miloradov, Mirjana B; Škrinjar, Marija M; Turk Sekulić, Maja M

    2017-01-02

    The objectives of the study were to determine the aflatoxin M1 content in human milk samples in Vojvodina, Serbia, and to assess the risk of infants' exposure to aflatoxins food contamination. The growth of Aspergillus flavus and production of aflatoxin B1 in corn samples resulted in higher concentrations of AFM1 in milk and dairy products in 2013, indicating higher concentrations of AFM1 in human milk samples in 2013 and 2014 in Serbia. A total number of 60 samples of human milk (colostrum and breast milk collected 4-8 months after delivery) were analyzed for the presence of AFM1 using the Enzyme Linked Immunosorbent Assay method. The estimated daily intake of AFM1 through breastfeeding was calculated for the colostrum samples using an average intake of 60 mL/kg body weight (b.w.)/day on the third day of lactation. All breast milk collected 4-8 months after delivery and 36.4% of colostrum samples were contaminated with AFM1. The greatest percentage of contaminated colostrum (85%) and all samples of breast milk collected 4-8 months after delivery had AFM1 concentration above maximum allowable concentration according to the Regulation on health safety of dietetic products. The mean daily intake of AFM1 in colostrum was 2.65 ng/kg bw/day. Results of our study indicate the high risk of infants' exposure, who are at the early stage of development and vulnerable to toxic contaminants.

  8. Effector molecules released by Th1 but not Th17 cells drive an M1 response in microglia.

    Science.gov (United States)

    Prajeeth, Chittappen K; Löhr, Kirsten; Floess, Stefan; Zimmermann, Julian; Ulrich, Reiner; Gudi, Viktoria; Beineke, Andreas; Baumgärtner, Wolfgang; Müller, Marcus; Huehn, Jochen; Stangel, Martin

    2014-03-01

    Microglia act as sensors of inflammation in the central nervous system (CNS) and respond to many stimuli. Other key players in neuroinflammatory diseases are CD4+ T helper cell (Th) subsets that characteristically secrete IFN-γ (Th1) or IL-17 (Th17). However, the potential of a distinct cytokine milieu generated by these effector T cell subsets to modulate microglial phenotype an