Predicting the spatial distribution of leaf litterfall in a mixed deciduous forest

NARCIS (Netherlands)

Staelens, Jeroen; Nachtergale, Lieven; Luyssaert, Sebastiaan

2004-01-01

An accurate prediction of the spatial distribution of litterfall can improve insight in the interaction between the canopy layer and forest floor characteristics, which is a key feature in forest nutrient cycling. Attempts to model the spatial variability of litterfall have been made across forest

Mortality and community changes drive sudden oak death impacts on litterfall and soil nitrogen cycling.

Science.gov (United States)

Cobb, Richard C; Eviner, Valerie T; Rizzo, David M

2013-10-01

Few studies have quantified pathogen impacts to ecosystem processes, despite the fact that pathogens cause or contribute to regional-scale tree mortality. We measured litterfall mass, litterfall chemistry, and soil nitrogen (N) cycling associated with multiple hosts along a gradient of mortality caused by Phytophthora ramorum, the cause of sudden oak death. In redwood forests, the epidemiological and ecological characteristics of the major overstory species determine disease patterns and the magnitude and nature of ecosystem change. Bay laurel (Umbellularia californica) has high litterfall N (0.992%), greater soil extractable NO3 -N, and transmits infection without suffering mortality. Tanoak (Notholithocarpus densiflorus) has moderate litterfall N (0.723%) and transmits infection while suffering extensive mortality that leads to higher extractable soil NO3 -N. Redwood (Sequoia sempervirens) has relatively low litterfall N (0.519%), does not suffer mortality or transmit the pathogen, but dominates forest biomass. The strongest impact of pathogen-caused mortality was the potential shift in species composition, which will alter litterfall chemistry, patterns and dynamics of litterfall mass, and increase soil NO3 -N availability. Patterns of P. ramorum spread and consequent mortality are closely associated with bay laurel abundances, suggesting this species will drive both disease emergence and subsequent ecosystem function. © 2013 The Authors. New Phytologist © 2013 New Phytologist Trust.

Biophysical controls on surface fuel litterfall and decomposition in the northern Rocky Mountains, USA

Science.gov (United States)

Robert E. Keane

2008-01-01

Litterfall and decomposition rates of the organic matter that comprise forest fuels are important to fire management, because they define fuel treatment longevity and provide parameters to design, test, and validate ecosystem models. This study explores the environmental factors that control litterfall and decomposition in the context of fuel management for several...

Effects of radiation, litterfall and throughfall on herbaceous biomass production in oak woodlands of Southern Portugal

International Nuclear Information System (INIS)

Nunes, J.; Sa, C.; Madeira, M.; Gazarini, L.

2002-01-01

Micro climatic characteristics (soil moisture, and air and soil temperature) were monitored both under and outside the influence of Quercus rotundifolia canopy. The influence of tree cover on biomass production of herbaceous vegetation was studied through the simulation of the physical and chemical effects associated to the tree canopy (radiation, litterfall, throughfall). Treatments were: control (T), radiation shortage (RR), application of leaf litter (F), application of leaflitter and radiation shortage (FRR) , application of throughfall (N) and application of throughfall and radiation shortage (NRR). Most of the times, and especially in winter, soil temperature was higher in areas not influenced by the canopies than in those under their influence. Soil moisture tended to decrease faster in the areas outside the canopy influence. Mean annual biomass production of the herbaceous vegetation was 159.5, 145.8, 132.2, 126.66, 134.9 and 173.1 g m2, respectively, in treatments C, RR, F, FRR, N and NRR. The N, P, K, Mg, Mn and Ca concentrations in the herbaceous biomass were generally higher in the shaded treatments. When the amount of nutrients accumulated in the herbaceous vegetation biomass was expressed on an area basis, the highest values were observed for treatment with throughfall application and radiation shortage. Besides the possible effects of the micro climatic characteristics, differences with respect to herbaceous vegetation production may be explained by the presence of litterfall, as well as by the nutrients present in the throughfall solution [pt

Effects of the interception of litterfall by the understory on carbon cycling in eucalyptus plantations of South China.

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Yang, Long; Wang, Jun; Huang, Yuhui; Hui, Dafeng; Wen, Meili

2014-01-01

For the purposes of forest restoration, carbon (C) fixation, and economic improvement, eucalyptus (Eucalyptus urophylla) has been widely planted in South China. The understory of eucalyptus plantations is often occupied by a dense community of the fern Dicranopteris dichotoma, which intercepts tree canopy leaf litter before it reaches the ground. To understand the effects of this interception of litterfall on C cycling in eucalyptus plantations, we quantified the mass of intercepted litter and the influences of litterfall interception on litter decomposition and soil respiration. The total mass of E. urophylla litterfall collected on the understory was similar to that collected by the traditional litter trap method. All of the eucalyptus litterfall is intercepted by the D. dichotoma canopy. Of the litterfall that was intercepted by D. dichotoma, 20-40% and 60-80% was intercepted by the top (50-100 cm) and bottom (0-50 cm) of the understory canopy, respectively. Intercepted litterfall decomposed faster at the bottom of understory canopy (at the base of the plants) than at the top, and decomposition was slower on the soil surface in the absence of understory than on any location in the understory canopy. Soil respiration was highest when both the understory and litter were present and was lowest when both the understory and litter were absent. These results indicate that litterfall interception changed carbon flow between aboveground and belowground through litter decomposition and soil respiration, which changed carbon cycling in eucalyptus plantations. The effects of the understory on litter decomposition and soil respiration should be considered in ecosystem carbon models.

Effects of the interception of litterfall by the understory on carbon cycling in eucalyptus plantations of South China.

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Long Yang

Full Text Available For the purposes of forest restoration, carbon (C fixation, and economic improvement, eucalyptus (Eucalyptus urophylla has been widely planted in South China. The understory of eucalyptus plantations is often occupied by a dense community of the fern Dicranopteris dichotoma, which intercepts tree canopy leaf litter before it reaches the ground. To understand the effects of this interception of litterfall on C cycling in eucalyptus plantations, we quantified the mass of intercepted litter and the influences of litterfall interception on litter decomposition and soil respiration. The total mass of E. urophylla litterfall collected on the understory was similar to that collected by the traditional litter trap method. All of the eucalyptus litterfall is intercepted by the D. dichotoma canopy. Of the litterfall that was intercepted by D. dichotoma, 20-40% and 60-80% was intercepted by the top (50-100 cm and bottom (0-50 cm of the understory canopy, respectively. Intercepted litterfall decomposed faster at the bottom of understory canopy (at the base of the plants than at the top, and decomposition was slower on the soil surface in the absence of understory than on any location in the understory canopy. Soil respiration was highest when both the understory and litter were present and was lowest when both the understory and litter were absent. These results indicate that litterfall interception changed carbon flow between aboveground and belowground through litter decomposition and soil respiration, which changed carbon cycling in eucalyptus plantations. The effects of the understory on litter decomposition and soil respiration should be considered in ecosystem carbon models.

Contrasting impacts of continuous moderate drought and episodic severe droughts on the aboveground-biomass increment and litterfall of three coexisting Mediterranean woody species.

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Liu, Daijun; Ogaya, Romà; Barbeta, Adrià; Yang, Xiaohong; Peñuelas, Josep

2015-11-01

Climate change is predicted to increase the aridity in the Mediterranean Basin and severely affect forest productivity and composition. The responses of forests to different timescales of drought, however, are still poorly understood because extreme and persistent moderate droughts can produce nonlinear responses in plants. We conducted a rainfall-manipulation experiment in a Mediterranean forest dominated by Quercus ilex, Phillyrea latifolia, and Arbutus unedo in the Prades Mountains in southern Catalonia from 1999 to 2014. The experimental drought significantly decreased forest aboveground-biomass increment (ABI), tended to increase the litterfall, and decreased aboveground net primary production throughout the 15 years of the study. The responses to the experimental drought were highly species-specific. A. unedo suffered a significant reduction in ABI, Q. ilex experienced a decrease during the early experiment (1999-2003) and in the extreme droughts of 2005-2006 and 2011-2012, and P. latifolia was unaffected by the treatment. The drought treatment significantly increased branch litterfall, especially in the extremely dry year of 2011, and also increased overall leaf litterfall. The drought treatment reduced the fruit production of Q. ilex, which affected seedling recruitment. The ABIs of all species were highly correlated with SPEI in early spring, whereas the branch litterfalls were better correlated with summer SPEIs and the leaf and fruit litterfalls were better correlated with autumn SPEIs. These species-specific responses indicated that the dominant species (Q. ilex) could be partially replaced by the drought-resistant species (P. latifolia). However, the results of this long-term study also suggest that the effect of drought treatment has been dampened over time, probably due to a combination of demographic compensation, morphological and physiological acclimation, and epigenetic changes. However, the structure of community (e.g., species composition

Effect of seasonal flooding cycle on litterfall production in alluvial rainforest on the middle Xingu River (Amazon basin, Brazil).

Science.gov (United States)

Camargo, M; Giarrizzo, T; Jesus, A J S

2015-08-01

The assumption for this study was that litterfall in floodplain environments of the middle Xingu river follows a pattern of seasonal variation. According to this view, litterfall production (total and fractions) was estimated in four alluvial rainforest sites on the middle Xingu River over an annual cycle, and examined the effect of seasonal flooding cycle. The sites included two marginal flooded forests of insular lakes (Ilha Grande and Pimentel) and two flooded forests on the banks of the Xingu itself (Boa Esperança and Arroz Cru). Total litterfall correlated with rainfall and river levels, but whereas the leaf and fruit fractions followed this general pattern, the flower fraction presented an inverse pattern, peaking in the dry season. The litterfall patterns recorded in the present study were consistent with those recorded at other Amazonian sites, and in some other tropical ecosystems.

A Global Database of Litterfall Mass and Litter Pool Carbon and Nutrients

Data.gov (United States)

National Aeronautics and Space Administration — Measurement data of aboveground litterfall and littermass and litter carbon, nitrogen, and nutrient concentrations were extracted from 685 original literature...

Litter Dynamics in a Forest Dune at Restinga da Marambaia, RJ, Brazil

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Rodrigo Camara

2018-03-01

Full Text Available ABSTRACT Restingas are extremely degraded, tropical sandy ecosystems and are poorly studied in terms of nutrient cycling. The present study aimed to evaluate litter dynamics in a forest dune at Restinga da Marambaia, RJ. Litterfall was collected monthly using two parallel transects installed 200 m apart from each other with 15 litter traps (0.25 m2, over two consecutive years. The litterfall was sorted into leaves, twigs, flowers, fruits, and refuse. Litter decomposition was evaluated by the ratio between litterfall and litter layer on the soil surface, which was estimated every four months by quadrats (0.25 m2 placed next to the litter traps. The average annual litterfall was low (6.8 t ha-1 year-1 , mostly constituted by leaves (70%, with the greatest deposits occurring during the rainy season. The decomposition rate was low (0.85 and the turnover time was long (439 days. This litter dynamic contributes to the nutrient economy.

Litterfall dynamics in a iron-rich rock outcrop complex in the southeastern portion of the Iron Quadrangle of Brazil

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Eduardo André Ribeiro Valim

2013-06-01

Full Text Available Ecosystems on cangas (duricrust present considerable heterogeneity of habitats due to microtopographic variations, soil accumulation and a variety of plant functional groups. Therefore, spatial and temporal ecosystem processes such as litterfall are to be expected to be large, and the absence of a level of productivity represents all the facets of iron-rich landscapes. We investigated litterfall in a iron-rich rock complex in the Iron Quadrangle of Brazil, with habitats formed on different evolutionary stages of the soil, resulting in a gradient of biomass, canopy cover and community structure. The measurements were made in open field areas, dominated by herb-shrub vegetation and interspersed with islands of dense vegetation in which there were individual trees, as well as in areas of semideciduous forest. The litterfall, especially that of leaf litter, followed the gradient of woody cover and was approximately two times greater in the forest formation. However, the spatial and temporal variations in deposition were greatest in the herb-shrub areas and least in the semideciduous forest area, intermediate values being obtained for the tree island areas. The peaks in litterfall also varied among habitats, occurring in some periods of the rainy season and during the transition from rainy to dry in the herb-shrub and tree island areas, whereas they occurred at the end of the dry season in the semideciduous forest area. The results show significant differences in the patterns of litterfall among different physiognomies within the same iron-rich rock complex, indicating the need for expanded studies, focusing on the flow of matter and energy in such environments.

26 CFR 1.401(m)-2 - ACP test.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 5 2010-04-01 2010-04-01 false ACP test. 1.401(m)-2 Section 1.401(m)-2 Internal... TAXES Pension, Profit-Sharing, Stock Bonus Plans, Etc. § 1.401(m)-2 ACP test. (a) Actual contribution percentage (ACP) test—(1) In general—(i) ACP test formula. A plan satisfies the ACP test for a plan year only...

quantity and quality of litterfall in pure pine and pine/gmelina mixed ...

African Journals Online (AJOL)

KOME

The quantity and nutrient composition of litterfall varies between tree species, ... quality in these plantations particularly in the south eastern part have not ... Research Institute of Nigeria (FRIN), Abia State, Nigeria that .... litter than deciduous vegetation (Vogt et al., 1986; Bray and .... Reiners, W. A. and Lang, G. E., 1987.

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

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Shoichi Fukui

2018-01-01

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

Atmospheric mercury deposition to forests in the eastern USA.

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Risch, Martin R; DeWild, John F; Gay, David A; Zhang, Leiming; Boyer, Elizabeth W; Krabbenhoft, David P

2017-09-01

Atmospheric mercury (Hg) deposition to forests is important because half of the land cover in the eastern USA is forest. Mercury was measured in autumn litterfall and weekly precipitation samples at a total of 27 National Atmospheric Deposition Program (NADP) monitoring sites in deciduous and mixed deciduous-coniferous forests in 16 states in the eastern USA during 2007-2014. These simultaneous, uniform, repeated, annual measurements of forest Hg include the broadest area and longest time frame to date. The autumn litterfall-Hg concentrations and litterfall mass at the study sites each year were combined with annual precipitation-Hg data. Rates of litterfall-Hg deposition were higher than or equal to precipitation-Hg deposition rates in 70% of the annual data, which indicates a substantial contribution from litterfall to total atmospheric-Hg deposition. Annual litterfall-Hg deposition in this study had a median of 11.7 μg per square meter per year (μg/m 2 /yr) and ranged from 2.2 to 23.4 μg/m 2 /yr. It closely matched modeled dry-Hg deposition, based on land cover at selected NADP Hg-monitoring sites. Mean annual atmospheric-Hg deposition at forest study sites exhibited a spatial pattern partly explained by statistical differences among five forest-cover types and related to the mapped density of Hg emissions. Forest canopies apparently recorded changes in atmospheric-Hg concentrations over time because litterfall-Hg concentrations decreased year to year and litterfall-Hg concentrations were significantly higher in 2007-2009 than in 2012-2014. These findings reinforce reported decreases in Hg emissions and atmospheric elemental-Hg concentrations during this same time period. Methylmercury (MeHg) was detected in all litterfall samples at all sites, compared with MeHg detections in less than half the precipitation samples at selected sites during the study. These results indicate MeHg in litterfall is a pathway into the terrestrial food web where it can

Atmospheric mercury deposition to forests in the eastern USA

International Nuclear Information System (INIS)

Risch, Martin R.; DeWild, John F.; Gay, David A.; Zhang, Leiming; Boyer, Elizabeth W.; Krabbenhoft, David P.

2017-01-01

Atmospheric mercury (Hg) deposition to forests is important because half of the land cover in the eastern USA is forest. Mercury was measured in autumn litterfall and weekly precipitation samples at a total of 27 National Atmospheric Deposition Program (NADP) monitoring sites in deciduous and mixed deciduous-coniferous forests in 16 states in the eastern USA during 2007–2014. These simultaneous, uniform, repeated, annual measurements of forest Hg include the broadest area and longest time frame to date. The autumn litterfall-Hg concentrations and litterfall mass at the study sites each year were combined with annual precipitation-Hg data. Rates of litterfall-Hg deposition were higher than or equal to precipitation-Hg deposition rates in 70% of the annual data, which indicates a substantial contribution from litterfall to total atmospheric-Hg deposition. Annual litterfall-Hg deposition in this study had a median of 11.7 μg per square meter per year (μg/m 2 /yr) and ranged from 2.2 to 23.4 μg/m 2 /yr. It closely matched modeled dry-Hg deposition, based on land cover at selected NADP Hg-monitoring sites. Mean annual atmospheric-Hg deposition at forest study sites exhibited a spatial pattern partly explained by statistical differences among five forest-cover types and related to the mapped density of Hg emissions. Forest canopies apparently recorded changes in atmospheric-Hg concentrations over time because litterfall-Hg concentrations decreased year to year and litterfall-Hg concentrations were significantly higher in 2007–2009 than in 2012–2014. These findings reinforce reported decreases in Hg emissions and atmospheric elemental-Hg concentrations during this same time period. Methylmercury (MeHg) was detected in all litterfall samples at all sites, compared with MeHg detections in less than half the precipitation samples at selected sites during the study. These results indicate MeHg in litterfall is a pathway into the terrestrial food web where it can

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

Energy Technology Data Exchange (ETDEWEB)

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

2002-07-01

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

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

Science.gov (United States)

2016-04-05

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

Produção de castanha e de folhada e concentração de nutrientes nas folhas de soutos submetidos a diferentes sistemas de mobilização do solo Chestnut and litterfall production and leaf nutrient concentration in chestnut groves submitted to different soil tillage systems

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F. Raimundo

2009-01-01

studied in a 50 year-old chestnut grove, located in Northeast Portugal. The experimental trial was installed in the beginning of 1996 and it was monitored for eight years. The treatments were: chisel plow (average depth 15 cm, which corresponds to the traditional tillage (MT; disc harrowing tillage, up to 7 cm depth (GD; rainfed seeded pasture, with leguminous and grasses species (PS; and no-tillage with spontaneous herbaceous vegetation (NM. Results, between 1999 and 2004, showed that the average production of litter-fall (leaves, burs, chestnuts and inflorescences, was greatest in NM treatment (755 g m-2, followed by the PS (729 g m-2, GD (708 g m-2 and MT (627 g m-2 treatment, although the differences were not significant. During that period, the burs (36.7% made the greatest contribution to total litter-fall, followed by the leaves (32.5%, chestnuts (24.7% and inflorescences (6.1%. The chestnut production was significantly lower in the MT (133 g m-2 treatment than in the NM (193 g m-2 and PS (191 g m-2. The N, P and Mg content in leaves were significantly lower in MT treatment than in the others; the K content was significantly lower in MT and PS treatments than in GD; the Ca concentration was significantly lower in MT treatment than in GD and PS. Management practices alternatives to the traditional soil tillage revealed to be more appropriated to enhance productivity of chestnut groves and to reduce production costs.

Input and turnover of forest tree litter in the Forsmark and Oskarshamn areas

Energy Technology Data Exchange (ETDEWEB)

Mjoefors, Kristina; Johansson, Maj-Britt; Nilsson, Aake [Dept. of Forest Soi ls, Swedish Univ. of Agricultural Sciences (Sweden); Hyvoenen, Riitta [Dept. of Eco logy, Swedish Univ. of Agricultural Sciences (Sweden)

2007-04-15

Forsmark sites, the N return in litterfall varied between 1.1 and 2.6 gdw/m{sup 2}/yr, the lower figure for site F3 and the higher for site F2. At site F1, about 1.7 gdw N/m{sup 2}/yr was deposited. The decomposition of the individual site litters was monitored over two years in field studies and the decomposition was predicted for up to 10 years using a dynamic decomposition model. At all three sites in the Forsmark area, the spruce needle litter lost around 33% in mass during the first year and after two years the cumulative mass loss amounted to 45%. The alder leaf litter decomposed more rapidly and lost 60% of mass during the first year and had reached a cumulative mass loss of 73% after two years. Generally, minor differences were noted in the decomposition pattern for the spruce and pine needles at sites within the Oskarshamn area. According to the model predictions, after 10 years about 80% of the initial mass was decomposed from needle litters and oak leaves but over 90% of the initial mass of alder leaves was decomposed. Mineralisation of N started immediately from alder leaves, and proceeded at a rapid rate during the first five months, after which it slowed down markedly. Due to its fast initial mineralisation, the alder litter lost about half its original amount of N during these first months. There was also generally a small loss of N from the other litter types during the first months but this loss was minor and never exceeded 10% of the initial N amount in the litter. The first phase of N loss was generally followed by short irregular periods when N was immobilised. Generally, 80-90% of the initial N amount still remained in the coniferous and oak litters after two years of decomposition (100% in the pine needles) whereas alder leaves had lost 60% of their N. The release of phosphorus (P) started immediately from all litter types and was most rapid from the alder leaf litter, which lost about 60% of its initial amount during the first five months. The other

Input and turnover of forest tree litter in the Forsmark and Oskarshamn areas

International Nuclear Information System (INIS)

Mjoefors, Kristina; Johansson, Maj-Britt; Nilsson, Aake; Hyvoenen, Riitta

2007-04-01

litterfall varied between 1.1 and 2.6 gdw/m 2 /yr, the lower figure for site F3 and the higher for site F2. At site F1, about 1.7 gdw N/m 2 /yr was deposited. The decomposition of the individual site litters was monitored over two years in field studies and the decomposition was predicted for up to 10 years using a dynamic decomposition model. At all three sites in the Forsmark area, the spruce needle litter lost around 33% in mass during the first year and after two years the cumulative mass loss amounted to 45%. The alder leaf litter decomposed more rapidly and lost 60% of mass during the first year and had reached a cumulative mass loss of 73% after two years. Generally, minor differences were noted in the decomposition pattern for the spruce and pine needles at sites within the Oskarshamn area. According to the model predictions, after 10 years about 80% of the initial mass was decomposed from needle litters and oak leaves but over 90% of the initial mass of alder leaves was decomposed. Mineralisation of N started immediately from alder leaves, and proceeded at a rapid rate during the first five months, after which it slowed down markedly. Due to its fast initial mineralisation, the alder litter lost about half its original amount of N during these first months. There was also generally a small loss of N from the other litter types during the first months but this loss was minor and never exceeded 10% of the initial N amount in the litter. The first phase of N loss was generally followed by short irregular periods when N was immobilised. Generally, 80-90% of the initial N amount still remained in the coniferous and oak litters after two years of decomposition (100% in the pine needles) whereas alder leaves had lost 60% of their N. The release of phosphorus (P) started immediately from all litter types and was most rapid from the alder leaf litter, which lost about 60% of its initial amount during the first five months. The other litter types generally lost around 10

Radiocesium transfer through aerial pathways in a South Carolina flooplain forest

International Nuclear Information System (INIS)

Shure, D.J.; Gottschalk, M.R.

1978-01-01

Cesium-137 cycling studies were conducted in a floodplain forest surrounding a reactor effluent stream at the Savannah River Plant in South Carolina. Throughfall, stem-flow, and litterfall pathways were studied along transects within a 1.5-ha area of floodplain forest. Annual precipitation totaled 1102 liters/m 2 in the study area. Approximately 88% of this rainfall reached the forest floor as throughfall and 4 to 6% as stemflow. Meteorological inputs (fallout) of 137 Cs totaled 3.2 nCi/m 2 for the year. An additional 11 to 15 nCi m -2 year -1 was leached from the floodplain vegetation as throughfall during precipiation. Radiocesium concentrations in throughfall and stem flow were highest in the fall when 137 Cs is readily leached from leaves before leaffall. Radiocesium concentrations in stemflow were always much higher than in throughfall, particularly during the nongrowing season. The annual 137 Cs transfer as stemflow was 2.5 to 4.1 nCi m -2 year -1 , however, which is considerably less (15 to 22%) than the total 137 Cs reaching the forest floor as throughfall. Radiocesium movement in annual litterfall is approximately equal to the total 137 Cs leached from floodplain vegetation during rainfall

McDonald 2.1-m and CRTS Photometry of Eclipsing Polars

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Wells, Natalie; Mason, Paul

2018-01-01

We present broadband optical photometry of five polars made using the 2.1-m telescope of McDonald Observatory. Four of the polars are eclipsing (EP Dra, FL Cet, V2301 Oph, and a Catalina Sky Survey (CSS) polar candidate). In addition, a pre-polar (MQ Dra) was observed. Typical integration times were 1-3 seconds with no dead time. At this time resolution, eclipse structure can be seen in both one- and two-pole accretors. McDonald 2.1-m data over several years is phased together with CSS photometry covering up to 7 years, in search of indications of period variation. Combining the high-resolution, high-speed photometry obtained using the ProEm camera on the McDonald 2.1-m with the sparse, but high-quality multi-year baseline photometry of the CSS places strong constraints on the time variability of the eclipse periods in these binary systems. In most cases, eclipse variations do not perfectly fit a linear ephemeris. We investigate the source of variations using standard O-C diagram techniques and period search algorithms.

Dinâmica sazonal da produção e decomposição de serrapilheira em floresta tropical de transição Seasonal dynamics of the litterfall production and decomposition in tropical transitional forest

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Luciana Sanches

2009-04-01

Full Text Available Em função de se analisar a produção, dinâmica e decomposição de serrapilheira em busca da sazonalidade do microclima em uma floresta tropical de transição Amazônia Cerrado, propõe-se estimar a produção de serrapilheira, por meio de caixas de coleta de 1 m² e o acúmulo de serrapilheira sobre o solo por meio de quadrantes de 25 x 25 cm, distribuídos aleatoriamente. Determinaram-se a constante de decaimento (K, o coeficiente de retorno de serrapilheira (K L e a constante de decomposição (K'. Com o emprego de bolsas de nylon preenchidas com folhas de espécies de relevância na floresta (Tovomita schomburgkki e Brosimium lactescens estudou-se a decomposição de folhas e se monitaram os fatores ambientais por meio de equipamentos instalados em uma torre micrometeorológica. A produção de serrapilheira não só se apresentou de forma sazonal, com significativa influência da umidade relativa do ar e da precipitação, em uma floresta de transição, mas foi majoritariamente composta de folhas seguidas de galhos e miscelânea (flores e frutos. A decomposição de folhas em florestas tropicais foi acelerada em ambas as estações, seca-úmida e úmida-seca, sendo a velocidade de decomposição das folhas maior na estação úmida-seca.The objective of this study was to analyze the production, dynamics and litter decomposition as a function of the seasonality of the microclimate in a transitional tropical forest of Amazonia Cerrado. Estimate of litterfall was carried out with collection boxes of 1 m² and floor forest mass with quadrants of 25 x 25 cm distributed randomly. The decline constant (K, litter turnover rate (K L and litter decomposition rate (K' were determined by estimation of litterfall and forest floor litter mass. Leaf decomposition was studied by litter bags with leaves of species of relevance (Tovomita schomburgkki and Brosimium lactescens in the forest. The analysis of the environmental factors was measured through

Enhanced M1/M2 macrophage ratio promotes orthodontic root resorption.

Science.gov (United States)

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

2015-01-01

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

Main: 1M2Q [RPSD[Archive

Lifescience Database Archive (English)

Full Text Available 1M2Q トウモロコシ Corn Zea mays L. Casein Kinase Ii, Alpha Chain Name=Ack2; Zea Mays Mole...cule: Casein Kinase Ii, Alpha Chain; Chain: A; Fragment: Catlytic Subunit; Synonym: Ckii; Engineered: Yes Tr...ansferase 2.7.1.37 (Casein Kinase Ii, Alpha Chain) E.De Moliner, S.Sarno, S.Moro, G.Zagotto, G.Zanotti, L.A....=2-326.|PDB; 1M2Q; X-ray; A=2-328.|PDB; 1M2R; X-ray; A=2-328.|PDB; 1OM1; X-ray; A=1-332.|Mai

Soil respiration patterns and rates at three Taiwanese forest plantations: dependence on elevation, temperature, precipitation, and litterfall.

Science.gov (United States)

Huang, Yu-Hsuan; Hung, Chih-Yu; Lin, I-Rhy; Kume, Tomonori; Menyailo, Oleg V; Cheng, Chih-Hsin

2017-11-15

Soil respiration contributes to a large quantity of carbon emissions in the forest ecosystem. In this study, the soil respiration rates at three Taiwanese forest plantations (two lowland and one mid-elevation) were investigated. We aimed to determine how soil respiration varies between lowland and mid-elevation forest plantations and identify the relative importance of biotic and abiotic factors affecting soil respiration. The results showed that the temporal patterns of soil respiration rates were mainly influenced by soil temperature and soil water content, and a combined soil temperature and soil water content model explained 54-80% of the variation. However, these two factors affected soil respiration differently. Soil temperature positively contributed to soil respiration, but a bidirectional relationship between soil respiration and soil water content was revealed. Higher soil moisture content resulted in higher soil respiration rates at the lowland plantations but led to adverse effects at the mid-elevation plantation. The annual soil respiration rates were estimated as 14.3-20.0 Mg C ha -1  year -1 at the lowland plantations and 7.0-12.2 Mg C ha -1  year -1 at the mid-elevation plantation. When assembled with the findings of previous studies, the annual soil respiration rates increased with the mean annual temperature and litterfall but decreased with elevation and the mean annual precipitation. A conceptual model of the biotic and abiotic factors affecting the spatial and temporal patterns of the soil respiration rate was developed. Three determinant factors were proposed: (i) elevation, (ii) stand characteristics, and (iii) soil temperature and soil moisture. The results indicated that changes in temperature and precipitation significantly affect soil respiration. Because of the high variability of soil respiration, more studies and data syntheses are required to accurately predict soil respiration in Taiwanese forests.

Litter mercury deposition in the Amazonian rainforest.

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Fostier, Anne Hélène; Melendez-Perez, José Javier; Richter, Larissa

2015-11-01

The objective of this work was to assess the flux of atmospheric mercury transferred to the soil of the Amazonian rainforest by litterfall. Calculations were based on a large survey of published and unpublished data on litterfall and Hg concentrations in litterfall samples from the Amazonian region. Litterfall based on 65 sites located in the Amazon rainforest averaged 8.15 ± 2.25 Mg ha(-1) y(-1). Average Hg concentrations were calculated from nine datasets for fresh tree leaves and ten datasets for litter, and a median concentration of 60.5 ng Hg g(-1) was considered for Hg deposition in litterfall, which averaged 49 ± 14 μg m(-2) yr(-1). This value was used to estimate that in the Amazonian rainforest, litterfall would be responsible for the annual removing of 268 ± 77 Mg of Hg, approximately 8% of the total atmospheric Hg deposition to land. The impact of the Amazon deforestation on the Hg biogeochemical cycle is also discussed. Copyright © 2015 Elsevier Ltd. All rights reserved.

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

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Shweta Joshi

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

Structural and functional characteristics of avicennia germinans mangrove formation of Chengue bay (Colombian Caribbean)

International Nuclear Information System (INIS)

Rodriguez Ramirez, Alberto; Nivia Ruiz, Jaime; Garzon Ferreira, Jaime

2004-01-01

Within the framework of the CARICOMP (Caribbean coastal marine productivity) monitoring program, a study of the avicennia germinans mangrove formation of Chengue bay (Tayrona natural park, Colombia) was performed between June 1995 and July 1996, based on the evaluation of structural and functional characteristics at three monitoring plots (10 x 10 m). The structure of the studied formation is coincident with that of fringing forests of the Caribbean region in having small trees (dbh=11.3 cm, total height=6.3 m) and high densities (16.3 trunks/0.01 ha). During the monitored period there was a low mortality rate (0.7 trees/year) and there were significant increases of the circumferences at breast height (as well as of the variables derived from this measure) average tree growth rates expressed in height, dbh and basal area were 26.7 cm/year, 0.17 cm/year and 2.9 cm/year respectively. Litterfall was composed principally by leaves (66.1%) and represented a mean production rate of 43.1 g/m2/month (5.2 t/ha/year). there was a temporal pattern of litterfall production associated with the climatic seasons in the area: during rainy months the production of total litterfall, leaves and fruits was higher, while during the dry season there was a reduction of these components and an increase of flowers and wood/twigs. therefore, flowering and fruit production periods are fitted to an annual reproductive cycle. In general, the information gathered during this study is a new contribution to the knowledge of mangrove ecology in Chengue and showed that the monitored trees had the conditions to grow and develop during the evaluated period

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

Science.gov (United States)

Kassaee, Mohamad Zaman; Ashenagar, Samaneh

2018-02-06

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

Impacts of increasing typhoons on the structure and function of a subtropical forest: reflections of a changing climate.

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Lin, Kuo-Chuan; Hamburg, Steven P; Wang, Lixin; Duh, Chin-Tzer; Huang, Chu-Mei; Chang, Chung-Te; Lin, Teng-Chiu

2017-07-07

Due to their destructive and sporadic nature, it is often difficult to evaluate and predict the effects of typhoon on forest ecosystem patterns and processes. We used a 21-yr record of litterfall rates to explore the influence of typhoon frequency and intensity, along with other meteorological variables, on ecosystem dynamics in a subtropical rainforest. Over the past half century there has been an increasing frequency of strong typhoons (category 3; >49.6 m s -1 ; increase of 1.5 typhoons/decade) impacting the Fushan Experimental Forest, Taiwan. At Fushan strong typhoons drive total litterfall mass with an average of 1100 kg ha -1 litterfall typhoon -1 . While mean typhoon season litterfall has been observed to vary by an order of magnitude, mean litterfall rates associated with annual leaf senescence vary by typhoon frequency, total annual litter mass increased gradually over the 21-year record following three major typhoons in 1994. Monthly maximum wind speed was predictive of monthly litterfall, yet the influence of precipitation and temperature was only evident in non-typhoon affected months. The response of this subtropical forest to strong typhoons suggests that increasing typhoon frequency has already shifted ecosystem structure and function (declining carbon sequestration and forest stature).

Diversification of the vacAs1m1 and vacAs2m2 strains of Helicobacter pylori in Meriones unguiculatus

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Sandra Mendoza Elizalde

2016-11-01

Full Text Available The bacterium Helicobacter pylori exhibits great genetic diversity, and the pathogenic roles of its virulence factors have been widely studied. However, the evolutionary dynamics of H. pylori strains during stomach colonization are not well characterized. Here, we analyzed the microevolutionary dynamics of the toxigenic strain vacAs1m1, the non-toxigenic strain vacAs2m2, and a combination of both strains in an animal model over time. Meriones unguiculatus were inoculated with the following bacteria: group 1–toxigenic strain vacAs1m1/cagA+/cagE+/babA2+; ST181, group 2–non-toxigenic strain vacAs2m2/ cagA+/ cagE+/ babA2+; ST2901, and group 3–both strains. The gerbils were euthanized at different time points (3, 6, 12 and 18 months. In group 1, genetic alterations were observed at 6 and 12 months. With the combination of both strains, group 3 also exhibited genetic alterations at 3 and 18 months; moreover, a chimera, vacA m1-m2, was detected. Additionally, four new sequence types (STs were reported in the PubMLST database for H. pylori. Synonymous and non-synonymous mutations were analyzed and associated with alterations in amino acids. Microevolutionary analysis of the STs (PHYLOViZ identified in each group revealed many mutational changes in the toxigenic (vacAs1m1 and non-toxigenic (vacAs2m2 strains. Phylogenetic assessments (eBURST did not reveal clonal complexes. Our findings indicate that the toxigenic strain, vacAs1m1, and a combination of toxigenic and non-toxigenic strains acquired genetic material by recombination. The allelic combination, vacAs2m1, displayed the best adaptation in the animal model over time, and a chimera, m1-m2, was also identified, which confirmed previous reports.

Rac1 Regulates the Activity of mTORC1 and mTORC2 and Controls Cellular Size

Science.gov (United States)

Saci, Abdelhafid; Cantley, Lewis C.; Carpenter, Christopher L.

2013-01-01

SUMMARY Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that exists in two separate complexes, mTORC1 and mTORC2, that function to control cell size and growth in response to growth factors, nutrients, and cellular energy levels. Low molecular weight GTP-binding proteins of the Rheb and Rag families are key regulators of the mTORC1 complex, but regulation of mTORC2 is poorly understood. Here, we report that Rac1, a member of the Rho family of GTPases, is a critical regulator of both mTORC1 and mTORC2 in response to growth-factor stimulation. Deletion of Rac1 in primary cells using an inducible-Cre/Lox approach inhibits basal and growth-factor activation of both mTORC1 and mTORC2. Rac1 appears to bind directly to mTOR and to mediate mTORC1 and mTORC2 localization at specific membranes. Binding of Rac1 to mTOR does not depend on the GTP-bound state of Rac1, but on the integrity of its C-terminal domain. This function of Rac1 provides a means to regulate mTORC1 and mTORC2 simultaneously. PMID:21474067

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

International Nuclear Information System (INIS)

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

2004-01-01

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

Homoleptic diphosphacyclobutadiene complexes [M(η(4)-P2C2R2)2]x- (M = Fe, Co; x = 0, 1).

Science.gov (United States)

Wolf, Robert; Ehlers, Andreas W; Khusniyarov, Marat M; Hartl, František; de Bruin, Bas; Long, Gary J; Grandjean, Fernande; Schappacher, Falko M; Pöttgen, Rainer; Slootweg, J Chris; Lutz, Martin; Spek, Anthony L; Lammertsma, Koop

2010-12-27

The preparation and comprehensive characterization of a series of homoleptic sandwich complexes containing diphosphacyclobutadiene ligands are reported. Compounds [K([18]crown-6)(thf)(2)][Fe(η(4)-P(2)C(2)tBu(2))(2)] (K1), [K([18]crown-6)(thf)(2)][Co(η(4)-P(2)C(2)tBu(2))(2)] (K2), and [K([18]crown-6)(thf)(2)][Co(η(4)-P(2)C(2)Ad(2))(2)] (K3, Ad = adamantyl) were obtained from reactions of [K([18]crown-6)(thf)(2)][M(η(4)-C(14)H(10))(2)] (M = Fe, Co) with tBuC[triple bond]P (1, 2), or with AdC[triple bond]P (3). Neutral sandwiches [M(η(4)-P(2)C(2)tBu(2))(2)] (4: M = Fe 5: M = Co) were obtained by oxidizing 1 and 2 with [Cp(2)Fe]PF(6). Cyclic voltammetry and spectro-electrochemistry indicate that the two [M(η(4)-P(2)C(2)tBu(2))(2)](-)/[M(η(4)-P(2)C(2)tBu(2))(2)] moieties can be reversibly interconverted by one electron oxidation and reduction, respectively. Complexes 1-5 were characterized by multinuclear NMR, EPR (1 and 5), UV/Vis, and Mössbauer spectroscopies (1 and 4), mass spectrometry (4 and 5), and microanalysis (1-3). The molecular structures of 1-5 were determined by using X-ray crystallography. Essentially D(2d)-symmetric structures were found for all five complexes, which show the two 1,3-diphosphacyclobutadiene rings in a staggered orientation. Density functional theory calculations revealed the importance of covalent metal-ligand π bonding in 1-5. Possible oxidation state assignments for the metal ions are discussed.

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

International Nuclear Information System (INIS)

Keinmeesuke, Sirichai

2002-01-01

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

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

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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.

Efficacy and Safety of Regorafenib With 2/1 Schedule for Patients ≥ 75 Years With Metastatic Colorectal Cancer (mCRC) After Failure of 2 Lines of Chemotherapy.

Science.gov (United States)

Petrioli, Roberto; Chirra, Martina; Messuti, Luciana; Fiaschi, Anna Ida; Savelli, Vinno; Martellucci, Ignazio; Francini, Edoardo

2018-02-21

In the CORRECT (patients with metastatic COloRectal Cancer treated with REgorafenib or plaCebo after failure of standard Therapy) trial, regorafenib was proven to extend survival of patients with metastatic colorectal cancer (mCRC) that progressed after all available therapies. Grade 3 to 4 toxicity occurred in 54% of patients, and data on the activity and tolerability of regorafenib in elderly patients were scarce. The aim of this study was to evaluate the efficacy and safety of an alternative schedule, 2-week-on treatment and 1 week-off (2/1 schedule), of regorafenib for elderly patients with mCRC. Patients ≥ 75 years with mCRC who progressed after oxaliplatin- and irinotecan-based chemotherapy received regorafenib on a 2/1 schedule. Potentially frail subjects were identified by G8 screening tool and excluded. The 2-month disease-control rate was the primary endpoint, and the secondary endpoints included safety, progression-free survival (PFS), overall survival (OS), and objective response rate. Between February 2014 and May 2017, 23 patients with mCRC were recruited at our institution. No partial or complete responses were observed, and the stable disease and disease-control rate were 52.2%. The median PFS was 4.8 months (95% confidence interval, 3.8-6.3 months), and the median OS was 8.9 months (95% confidence interval, 6.9-10.6 months). Adverse events were uncommon, and the most frequent grade 3 toxicity adverse events were hand-foot skin reaction (9%) and fatigue (9%). Toxicity-related dose reductions and discontinuations occurred in 5 and 2 patients, respectively. Regorafenib administered with a modified 2/1 schedule to patients who were aged ≥ 75 years and non-frail with treatment-refractory mCRC seems to be tolerable and achieve encouraging results in terms of PFS and OS. Copyright © 2018. Published by Elsevier Inc.

Plant n-alkane production from litterfall altered the diversity and community structure of alkane degrading bacteria in litter layer in lowland subtropical rainforest in Taiwan

Science.gov (United States)

Huang, Tung-Yi; Hsu, Bing-Mu; Chao, Wei-Chun; Fan, Cheng-Wei

2018-03-01

n-Alkane and alkane-degrading bacteria have long been used as crucial biological indicators of paleoecology, petroleum pollution, and oil and gas prospecting. However, the relationship between n-alkane and alkane-degrading bacteria in natural forests is still poorly understood. In this study, long-chain n-alkane (C14-C35) concentrations in litterfall, litter layer, and topsoil as well as the diversity and abundance of n-alkane-degrading bacterial communities in litter layers were investigated in three habitats across a lowland subtropical rainforest in southern Taiwan: ravine, windward, and leeward habitats in Nanjenshan. Our results demonstrate that the litterfall yield and productivity of long-chain n-alkane were highest in the ravine habitats. However, long-chain n-alkane concentrations in all habitats were decreased drastically to a similar low level from the litterfall to the bulk soil, suggesting a higher rate of long-chain n-alkane degradation in the ravine habitat. Operational taxonomic unit (OTU) analysis using next-generation sequencing data revealed that the relative abundances of microbial communities in the windward and leeward habitats were similar and different from that in the ravine habitat. Data mining of community amplicon sequencing using the NCBI database revealed that alkB-gene-associated bacteria (95 % DNA sequence similarity to alkB-containing bacteria) were most abundant in the ravine habitat. Empirical testing of litter layer samples using semi-quantitative polymerase chain reaction for determining alkB gene levels confirmed that the ravine habitat had higher alkB gene levels than the windward and leeward habitats. Heat map analysis revealed parallels in pattern color between the plant and microbial species compositions of the habitats, suggesting a causal relationship between the plant n-alkane production and microbial community diversity. This finding indicates that the diversity and relative abundance of microbial communities in the

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

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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

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

Science.gov (United States)

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

2013-01-01

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

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

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

2016-01-01

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

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

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

2016-01-01

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

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

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

2017-08-01

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

MNK Controls mTORC1:Substrate Association through Regulation of TELO2 Binding with mTORC1

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Michael C. Brown

2017-02-01

Full Text Available The mechanistic target of rapamycin (mTOR integrates numerous stimuli and coordinates the adaptive response of many cellular processes. To accomplish this, mTOR associates with distinct co-factors that determine its signaling output. While many of these co-factors are known, in many cases their function and regulation remain opaque. The MAPK-interacting kinase (MNK contributes to rapamycin resistance in cancer cells. Here, we demonstrate that MNK sustains mTORC1 activity following rapamycin treatment and contributes to mTORC1 signaling following T cell activation and growth stimuli in cancer cells. We determine that MNK engages with mTORC1, promotes mTORC1 association with the phosphatidyl inositol 3′ kinase-related kinase (PIKK stabilizer, TELO2, and facilitates mTORC1:substrate binding. Moreover, our data suggest that DEPTOR, the endogenous inhibitor of mTOR, opposes mTORC1:substrate association by preventing TELO2:mTORC1 binding. Thus, MNK orchestrates counterbalancing forces that regulate mTORC1 enzymatic activity.

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

International Nuclear Information System (INIS)

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

1982-01-01

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

E2F1 regulates cellular growth by mTORC1 signaling.

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Sebastian Real

2011-01-01

Full Text Available During cell proliferation, growth must occur to maintain homeostatic cell size. Here we show that E2F1 is capable of inducing growth by regulating mTORC1 activity. The activation of cell growth and mTORC1 by E2F1 is dependent on both E2F1's ability to bind DNA and to regulate gene transcription, demonstrating that a gene induction expression program is required in this process. Unlike E2F1, E2F3 is unable to activate mTORC1, suggesting that growth activity could be restricted to individual E2F members. The effect of E2F1 on the activation of mTORC1 does not depend on Akt. Furthermore, over-expression of TSC2 does not interfere with the effect of E2F1, indicating that the E2F1-induced signal pathway can compensate for the inhibitory effect of TSC2 on Rheb. Immunolocalization studies demonstrate that E2F1 induces the translocation of mTORC1 to the late endosome vesicles, in a mechanism dependent of leucine. E2F1 and leucine, or insulin, together affect the activation of S6K stronger than alone suggesting that they are complementary in activating the signal pathway. From these studies, E2F1 emerges as a key protein that integrates cell division and growth, both of which are essential for cell proliferation.

CYP1A1 m1 and m2 polymorphisms: genetic susceptibility to lung cancer

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Paula Mota

2010-01-01

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

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

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

2017-01-01

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

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

International Nuclear Information System (INIS)

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

2015-01-01

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

Internal (m=1, n=1) and (m=2, n=1) resistive modes in the toroidal tokamak with circular cross-section

International Nuclear Information System (INIS)

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

1977-01-01

A linear analysis is presented of the toroidal coupling between the internal resistive modes (m=1, n=1) and (m=2, n=1) in the tokamak with circular cross-section. The resistive and diamagnetic effects are included in the singular layers where the safety factor q takes respectively the values one and two. By expanding the MHD equations in powers of epsilon, the local inverse of the aspect ratio, a system of two coupled equations is obtained for the harmonic amplitudes. When the shear is finite on q=1 the toroidal coupling is negligible. In the opposite limit, one can explain (a) the experimental behaviour of the (m=1, n=1) mode before the internal disruption, and (b) the simultaneous observation of the modes (m=1, n=1) and (m=2, n=1) before the main disruption. (author)

Litter mercury deposition in the Amazonian rainforest

International Nuclear Information System (INIS)

Fostier, Anne Hélène; Melendez-Perez, José Javier; Richter, Larissa

2015-01-01

The objective of this work was to assess the flux of atmospheric mercury transferred to the soil of the Amazonian rainforest by litterfall. Calculations were based on a large survey of published and unpublished data on litterfall and Hg concentrations in litterfall samples from the Amazonian region. Litterfall based on 65 sites located in the Amazon rainforest averaged 8.15 ± 2.25 Mg ha"−"1 y"−"1. Average Hg concentrations were calculated from nine datasets for fresh tree leaves and ten datasets for litter, and a median concentration of 60.5 ng Hg g"−"1 was considered for Hg deposition in litterfall, which averaged 49 ± 14 μg m"−"2 yr"−"1. This value was used to estimate that in the Amazonian rainforest, litterfall would be responsible for the annual removing of 268 ± 77 Mg of Hg, approximately 8% of the total atmospheric Hg deposition to land. The impact of the Amazon deforestation on the Hg biogeochemical cycle is also discussed. - Highlights: • Based on published data we estimated the litterfall in the Amazonian rainforest. • All the published data on Hg concentration in leaves and litter from the region and some unpublished data are presented. • We calculated the litter mercury deposition. • We estimated the contribution of dry, wet and litter Hg deposition in the Amazonian rainforest. • We also discussed the impact of Amazon deforestation on the Hg biogeochemical cycle. - The Amazonian rainforest is responsible for removing at least 268 Mg Hg y"−"1, 8% of the total atmospheric mercury deposition to land.

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

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

2017-10-01

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

On the simultaneous Pell equations x 2 - (4m 2 - 1)y 2 = y 2 - pz 2 ...

African Journals Online (AJOL)

Let m be a positive integer, and let p be an odd prime. By using certain properties of Pell and quartic diophantine equations with some elementary number theory methods, we prove that the system of equations x2 - (4m2 - 1)y2 = 1 and y2 - pz2 = 1 has positive integer solutions (x, y, z) if and only if p ≡ 7(mod 8) and m = 1/4 ...

2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA)

DEFF Research Database (Denmark)

Goldhirsch, Aron; Gelber, Richard D; Piccart-Gebhart, Martine J

2013-01-01

Trastuzumab has established efficacy against breast cancer with overexpression or amplification of the HER2 oncogene. The standard of care is 1 year of adjuvant trastuzumab, but the optimum duration of treatment is unknown. We compared 2 years of treatment with trastuzumab with 1 year of treatment......, and updated the comparison of 1 year of trastuzumab versus observation at a median follow-up of 8 years, for patients enrolled in the HERceptin Adjuvant (HERA) trial....

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

Science.gov (United States)

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

2016-03-01

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

Produção de serrapilheira no Cerrado e Floresta de Transição Amazônia-Cerrado do Centro-Oeste Brasileiro Litterfall production in the Brazilian mid-western Amazonia-Cerrado transition forest

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Carlos José da Silva

2007-01-01

Full Text Available O presente trabalho teve como objetivo verificar a variação da produção de serrapilheira de diferentes biomas: Cerrado (com as fitofisionomias Cerrado sensu stricto e Cerradão e Floresta de Transição Amazônia-Cerrado, em clima tropical. Para a determinação da produção de serrapilheira foram utilizados coletores de tela em náilon. Dados micrometereológicos foram coletados nas áreas de estudo. A produção de serrapilheira nos dois biomas mostrou acentuada sazonalidade, com as maiores produções ocorrendo durante a estação seca e menor durante a estação chuvosa. A maior produção de serrapilheira ocorreu na Floresta de Transição, seguida do bioma Cerrado. A fração de folhas foi mais representativa do que as frações de galhos, flores, frutos em ambas as áreas estudadas.The objective of the present work was to verify the variation of litterfall production of different biomass: a cerrado ("savanna" with vegetation types Cerrado sensu stricto ("orchard-like vegetation" and Cerradão ("woodland-like vegetation" and Amazonia-Cerrado transition forest in a tropical climate. To determine the litterfall production, we used nylon screen traps. Micrometereologic data was collected in both areas of study. The litterfall in two biomass revealed themselves as seasonal, with the highest productions occurring during the dry season and the lowest during the wet. The biggest litterfall occurred in the Transition Forest, followed by the Cerrado biome. Leaf fraction was more representative than twigs, flowers, fruits in both areas studied.

Models for financial crisis detection in Indonesia based on M1, M2 per foreign exchange reverse, and M2 multiplier indicators

Science.gov (United States)

Sugiyanto; Zukhronah, Etik; Pratiwi, Esteti Sophia

2017-12-01

Indonesia has been hit by financial crisis in the middle of 1997. The financial crisis that has occurred gives a severe impact to the economy of Indonesia resulting the needs for a detection system of financial crisis. Crisis can be detected based on several indicators such as M1, M2 per foreign exchange reserves, and M2 multiplier. These three indicators can affect the exchange rate stability and may further affect the financial stability so that it can be one of the causes of the financial crisis. This research aims to determine the appropriate model that can detect the financial crisis in Indonesia. Markov switching is an alternative model that can be approach and used often for detecting financial crisis. We can determine the combination of volatility and Markov switching model with AR and volatility model are determined first. The results of this research are that M1 can be modelled by SWARCH (3, 1) while M2 per foreign research exchange reserves and M2 multiplier can be modelled by SWARCH(3,2).

Abnormal glomerular filtration rate in children, adolescents and young adults starts below 75 mL/min/1.73 m(2).

Science.gov (United States)

Pottel, Hans; Hoste, Liesbeth; Delanaye, Pierre

2015-05-01

The chronic kidney disease (CKD) classification system for children is similar to that for adults, with both mainly based on estimated glomerular filtration rate (eGFR) combined with fixed cut-off values. The main cut-off eGFR value used to define CKD is 60 mL/min/1.73 m(2), a value that is also applied for children older than 2 years of age, adolescents and young adults. Based on a literature search, we evaluated inclusion criteria for eGFR in clinical trials or research studies on CKD for children. We also collected information on direct measurements of GFR (mGFR) in children and adolescents, with the aim to estimate the normal reference range for GFR. Using serum creatinine (Scr) normal reference values and Scr-based eGFR-equations, we also evaluated the correspondence between Scr normal reference values and (e)GFR normal reference values. Based on our literature search, the inclusion of children in published CKD studies has been based on cut-off values for eGFR of >60 mL/min/1.73 m(2). The lower reference limits for mGFR far exceed this adult threshold. Using eGFR values calculated using Scr-based formulas, we found that abnormal Scr levels in children already correspond to eGFR values that are below a cut-off of 75 mL/min/1.73 m(2). Abnormal GFR in children, adolescents and young adults starts below 75 mL/min/1.73 m(2), and as abnormality is a sign of disease, we recommend referring children, adolescents and young adults with an (e)GFR of <75 mL/min/1.73 m(2) for further clinical assessment.

Charge Transfer Effects in Naturally Occurring van der Waals Heterostructures (PbSe )1.16(TiSe2 )m (m =1 , 2)

Science.gov (United States)

Yao, Q.; Shen, D. W.; Wen, C. H. P.; Hua, C. Q.; Zhang, L. Q.; Wang, N. Z.; Niu, X. H.; Chen, Q. Y.; Dudin, P.; Lu, Y. H.; Zheng, Y.; Chen, X. H.; Wan, X. G.; Feng, D. L.

2018-03-01

van der Waals heterostructures (VDWHs) exhibit rich properties and thus has potential for applications, and charge transfer between different layers in a heterostructure often dominates its properties and device performance. It is thus critical to reveal and understand the charge transfer effects in VDWHs, for which electronic structure measurements have proven to be effective. Using angle-resolved photoemission spectroscopy, we studied the electronic structures of (PbSe )1.16(TiSe2 )m (m =1 , 2), which are naturally occurring VDWHs, and discovered several striking charge transfer effects. When the thickness of the TiSe2 layers is halved from m =2 to m =1 , the amount of charge transferred increases unexpectedly by more than 250%. This is accompanied by a dramatic drop in the electron-phonon interaction strength far beyond the prediction by first-principles calculations and, consequently, superconductivity only exists in the m =2 compound with strong electron-phonon interaction, albeit with lower carrier density. Furthermore, we found that the amount of charge transferred in both compounds is nearly halved when warmed from below 10 K to room temperature, due to the different thermal expansion coefficients of the constituent layers of these misfit compounds. These unprecedentedly large charge transfer effects might widely exist in VDWHs composed of metal-semiconductor contacts; thus, our results provide important insights for further understanding and applications of VDWHs.

mPGES-1-derived PGE2 mediates dehydration natriuresis

Science.gov (United States)

Jia, Zhanjun; Liu, Gang; Sun, Ying; Kakizoe, Yutaka; Guan, Guangju; Zhang, Aihua; Zhou, Shu-Feng

2013-01-01

PGE2 is a natriuretic factor whose production is elevated after water deprivation (WD) but its role in dehydration natriuresis is not well-defined. The goal of the present study was to investigate the role of microsomal prostaglandin E synthase-1 (mPGES-1) in dehydration natriuresis. After 24-h WD, wild-type (WT) mice exhibited a significant increase in 24-h urinary Na+ excretion accompanied with normal plasma Na+ concentration and osmolality. In contrast, WD-induced elevation of urinary Na+ excretion was completely abolished in mPGES-1 knockout (KO) mice in parallel with increased plasma Na+ concentration and a trend increase in plasma osmolality. WD induced a 1.8-fold increase in urinary PGE2 output and a 1.6-fold increase in PGE2 content in the renal medulla of WT mice, both of which were completely abolished by mPGES-1 deletion. Similar patterns of changes were observed for urinary nitrate/nitrite and cGMP. The natriuresis in dehydrated WT mice was associated with a significant downregulation of renal medullary epithelial Na channel-α mRNA and protein, contrasting to unaltered expressions in dehydrated KO mice. By quantitative RT-PCR, WD increased the endothelial nitric oxide synthase (eNOS), inducible NOS, and neuronal NOS expressions in the renal medulla of WT mice by 3.9-, 1.48-, and 2.6-fold, respectively, all of which were significantly blocked in mPGES-1 KO mice. The regulation of eNOS expression was further confirmed by immunoblotting. Taken together, our results suggest that mPGES-1-derived PGE2 contributes to dehydration natriuresis likely via NO/cGMP. PMID:23171554

26 CFR 1.806-2 - Taxable years affected.

Science.gov (United States)

2010-04-01

... 26 Internal Revenue 8 2010-04-01 2010-04-01 false Taxable years affected. 1.806-2 Section 1.806-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) INCOME TAX (CONTINUED) INCOME TAXES Investment Income § 1.806-2 Taxable years affected. Section 1.806-1 is applicable only to...

Selective mGAT2 (BGT-1) GABA Uptake Inhibitor

DEFF Research Database (Denmark)

Vogensen, Stine Byskov; Jørgensen, Lars; Madsen, Karsten Kirkegaard

2013-01-01

β-Amino acids sharing a lipophilic diaromatic side chain were synthesized and characterized pharmacologically on mouse GABA transporter subtypes mGAT1−4. The parent amino acids were also characterized. Compounds 13a, 13b, and 17b displayed more than 6-fold selectivity for mGAT2 over mGAT1. Compou...... 17b displayed anticonvulsive properties inferring a role of mGAT2 in epileptic disorders. These results provide new neuropharmacological tools and a strategy for designing subtype selective GABA transport inhibitors....

Leaf area and foliar biomass relationships in northern hardwood forests located along an 800 km acid deposition gradient

International Nuclear Information System (INIS)

Burton, A.J.; Pregitzer, K.S.; Reed, D.D.

1991-01-01

The canopies of northern hardwood forests dominated by sugar maple (Acer saccharum Marsh.) were examined at five locations spanning 800 km along an acid deposition and climatic gradient in the Great Lakes region. Leaf area index (LAI) calculated from litterfall ranged from 6.0 to 8.0 in 1988, from 4.9 to 7.9 in 1989, and from 5.3 to 7.8 in 1990. The data suggest that maximum LAI for the sites is between 7 and 8. Insect defoliation and the allocation of assimilates to reproductive parts in large seed years reduced LAI by up to 34%. Allometric equations for leaf area and foliar biomass were not significantly different among sites. They predicted higher LAI values than were estimated from litterfall and could not account for the influences of defoliation and seed production. Canopy transmittance was a viable alternative for estimating LAI. Extinction coefficients (K) of 0.49 to 0.65 were appropriate for solar elevations of 63 degree to 41 degree. Patterns of specific leaf area (SLA) were similar for the sites. Average sugar maple SLA increased from 147 cm 2 g -1 in the upper 5 m of the canopy to 389 cm 2 g -1 in the seeding layer. Litterfall SLA averaged 196 cm 2 g -1 for all species and 192 cm 2 g -1 for sugar maple. Similarity among the sites in allometric relationships, maximum LAI, canopy transmittance, and patterns of SLA suggests these characteristics were controlled primarily by the similar nutrient and moisture availability at the sites. A general increasing trend in litter production along the gradient could not be attributed to N deposition or length of growing season due to year to year variability resulting from insect defoliation and seed production

The mutual dependence of M1 fertility and M2 mutations in rice

International Nuclear Information System (INIS)

Gopinathan Nair, V.

1982-01-01

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

Autoradiography of H-3-pirenzepine and H-3-AFDX-384 in Mouse Brain Regions: Possible Insights into M-1, M-2, and M-4 Muscarinic Receptors Distribution

Czech Academy of Sciences Publication Activity Database

Valuskova, P.; Farar, V.; Forczek, Sándor; Křížová, I.; Mysliveček, J.

2018-01-01

Roč. 9, FEB 20 (2018), č. článku 124. ISSN 1663-9812 Institutional support: RVO:61389030 Keywords : 3 h-afdx-384 * 3 H-pirenzepine * 3 h-qnb * Autoradiography * M muscarinic receptor 1 * M muscarinic receptor 2 * M muscarinic receptor 4 Subject RIV: FH - Neurology OBOR OECD: Neurosciences (including psychophysiology Impact factor: 4.400, year: 2016

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

International Nuclear Information System (INIS)

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

1976-01-01

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

Sestrin2 inhibits mTORC1 through modulation of GATOR complexes

Energy Technology Data Exchange (ETDEWEB)

Kim, Jeong Sig; Ro, Seung-Hyun; Kim, Myungjin; Park, Hwan-Woo; Semple, Ian A.; Park, Haeli; Cho, Uhn-Soo; Wang, Wei; Guan, Kun-Liang; Karin, Michael; Lee, Jun Hee (Michigan); (UCSD)

2015-03-30

Sestrins are stress-inducible metabolic regulators that suppress a wide range of age- and obesity-associated pathologies, many of which are due to mTORC1 overactivation. Upon various stresses, the Sestrins inhibit mTORC1 activity through an indirect mechanism that is still unclear. GATORs are recently identified protein complexes that regulate the activity of RagB, a small GTPase essential for mTORC1 activation. GATOR1 is a GTPase activating protein (GAP) for RagB whereas GATOR2 functions as an inhibitor of GATOR1. However, how the GATORs are physiologically regulated is unknown. Here we show that Sestrin2 binds to GATOR2, and liberates GATOR1 from GATOR2-mediated inhibition. Released GATOR1 subsequently binds to and inactivates RagB, ultimately resulting in mTORC1 suppression. Consistent with this biochemical mechanism, genetic ablation of GATOR1 nullifies the mTORC1-inhibiting effect of Sestrin2 in both cell culture and Drosophila models. Collectively, we elucidate a new signaling cascade composed of Sestrin2-GATOR2-GATOR1-RagB that mediates stress-dependent suppression of mTORC1 activity.

Th1/M1 conversion to Th2/M2 responses in models of inflammation lacking cell death stimulates maturation of monocyte precursors to fibroblasts

Directory of Open Access Journals (Sweden)

JoAnn eTrial

2013-09-01

Full Text Available We have demonstrated that cardiac fibrosis arises from the differentiation of monocyte-derived fibroblasts. We present here evidence that this process requires sequential Th1 and Th2 induction promoting analogous M1 (classically activated and M2 (alternatively activated macrophage polarity. Our models are 1 mice subjected to daily repetitive ischemia reperfusion (I/R without infarction and 2 the in vitro transmigration of human mononuclear leukocytes through human cardiac microvascular endothelium. In the mouse heart, leukocytes entered after I/R in response to monocyte chemoattractant protein-1 (MCP-1 which is the major cytokine induced by this protocol. Monocytes within the heart then differentiated into fibroblasts making collagen while bearing the markers of M2 macrophages. T cells were seen in these hearts as well as in the human heart with cardiomyopathy. In the in vitro model, transmigration of the leukocytes was likewise induced by MCP-1 and some monocytes matured into fibroblasts bearing M2 markers. In this model, the MCP-1 stimulus induced a transient Th1 and M1 response that developed into a predominately Th2 and M2 response. An increase in the Th2 product IL-13 was present in both the human and the mouse models, consistent with its known role in fibrosis. In these simplified models, in which there is no cell death to stimulate an anti-inflammatory response, there is nonetheless a resolution of inflammation enabling a profibrotic environment. This induces the maturation of monocyte precursors into fibroblasts.

M-theory solutions invariant under D(2,1; γ) + D(2,1;γ)

International Nuclear Information System (INIS)

Bachas, C.; D'Hoker, E.; Estes, J.; Krym, D.

2014-01-01

We simplify and extend the construction of half-BPS solutions to 11-dimensional supergravity, with isometry superalgebra D(2,1;γ) + D(2,1;γ). Their space-time has the form AdS 3 x S 3 x S 3 warped over a Riemann surface Σ. It describes near-horizon geometries of M2 branes ending on, or intersecting with, M5 branes along a common string. The general solution to the BPS equations is specified by a reduced set of data (γ, h, G), where γ is the real parameter of the isometry superalgebra, and h and G are functions on Σ whose differential equations and regularity conditions depend only on the sign of γ. The magnitude of γ enters only through the map of h,G onto the supergravity fields, thereby promoting all solutions into families parametrized by vertical stroke γ vertical stroke. By analyzing the regularity conditions for the supergravity fields, we prove two general theorems: (i) that the only solution with a 2-dimensional CFT dual is AdS 3 x S 3 x S 3 x R 2 , modulo discrete identifications of the flat R 2 , and (ii) that solutions with γ 4 /Z 2 or AdS 7 ' regions; highly-curved M5-branes; and a coordinate singularity called the ''cap''. By putting these ''Lego'' pieces together we recover all known global regular solutions with the above symmetry, including the self-dual strings on M5 for γ 0, but now promoted to families parametrized by vertical stroke γ vertical stroke. We also construct exactly new regular solutions which are asymptotic to AdS 4 /Z 2 for γ 0 solutions with highly curved M5-brane regions, which are the formal continuation of the self-dual string solutions across the decompactification point at γ = 0. (Copyright copyright 2014 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

Reexamination of M2,3 atomic level widths and L1M2,3 transition energies of elements 69≤Z≤95

Science.gov (United States)

Fennane, K.; Berset, M.; Dousse, J.-Cl.; Hoszowska, J.; Raboud, P.-A.; Campbell, J. L.

2013-11-01

We report on high-resolution measurements of the photoinduced L1M2 and L1M3 x-ray emission lines of 69Tm, 70Yb, 71Lu, 73Ta, 74W, 75Re, 77Ir, 81Tl, 83Bi, and 95Am. From the linewidths of the measured transitions an accurate set of M2 and M3 level widths is determined assuming for the L1 level widths the values reported by Raboud [P.-A. Raboud et al., Phys. Rev. APLRAAN1050-294710.1103/PhysRevA.65.022512 65, 022512 (2002)]. Furthermore, the present experimental M2,3 data set is extended to 80Hg, 90Th, and 92U, using former L1M2,3 high-resolution x-ray emission spectroscopy measurements performed by our group. A detailed comparison of the M2 and M3 level widths determined in the present work with those recommended by Campbell and Papp [J. L. Campbell and T. Papp, At. Data Nucl. Data TablesADNDAT0092-640X10.1006/adnd.2000.0848 77, 1 (2001)] and other available experimental data as well as theoretical predictions is done. The observed abrupt changes of the M2,3 level widths versus atomic number Z can be explained satisfactorily by the cutoffs and onsets of the M2M4N1, respectively M3M4N3,4,5 and M3M5N2,3 Coster-Kronig transitions deduced from the semiempirical (Z+1) approximation. As a spin-off result of this study, precise L1M2 and L1M3 transition energies are obtained for the investigated elements. A very good agreement with transition energies calculated within the many-body perturbation theory is found.

Long non-coding RNA cox-2 prevents immune evasion and metastasis of hepatocellular carcinoma by altering M1/M2 macrophage polarization.

Science.gov (United States)

Ye, Yibiao; Xu, Yunxiuxiu; Lai, Yu; He, Wenguang; Li, Yanshan; Wang, Ruomei; Luo, Xinxi; Chen, Rufu; Chen, Tao

2018-03-01

Macrophages have been shown to demonstrate a high level of plasticity, with the ability to undergo dynamic transition between M1 and M2 polarized phenotypes. We investigate long non-coding RNA (lncRNA) cox-2 in macrophage polarization and the regulatory mechanism functions in hepatocellular carcinoma (HCC). Lipopolysaccharide (LPS) was used to induce RAW264.7 macrophages into M1 type, and IL-4 was to induce RAW264.7 macrophages into M2 type. We selected mouse hepatic cell line Hepal-6 and hepatoma cell line HepG2 for co-incubation with M1 or M2 macrophages. Quantitative real-time PCR was used to detect the expressions of lncRNA cox-2 and mRNAs. ELISA was conducted for testing IL-12 and IL-10 expressions; Western blotting for epithelial mesenchymal transition related factors (E-cadherin and Vimentin). An MTT, colony formation assay, flow cytometry, transwell assay, and stretch test were conducted to test cell abilities. The M1 macrophages had higher lncRNA cox-2 expression than that in the non-polarized macrophages and M2 macrophages. The lncRNA cox-2 siRNA decreased the expression levels of IL-12, iNOS, and TNF-α in M1 macrophages, increased the expression levels of IL-10, Arg-1, and Fizz-1 in M2 macrophages (all P evasion and tumor growth by inhibiting the polarization of M2 macrophages. © 2017 Wiley Periodicals, Inc.

PGE2-induced colon cancer growth is mediated by mTORC1

International Nuclear Information System (INIS)

Dufour, Marc; Faes, Seraina; Dormond-Meuwly, Anne; Demartines, Nicolas; Dormond, Olivier

2014-01-01

Highlights: • PGE 2 activates mTORC1 in colon cancer cells. • Inhibition of mTORC1 blocks PGE 2 induced colon cancer cell growth. • mTORC1 is a signaling intermediary in PGE 2 induced colon cancer cell responses. - Abstract: The inflammatory prostaglandin E 2 (PGE 2 ) cytokine plays a key role in the development of colon cancer. Several studies have shown that PGE 2 directly induces the growth of colon cancer cells and furthermore promotes tumor angiogenesis by increasing the production of the vascular endothelial growth factor (VEGF). The signaling intermediaries implicated in these processes have however not been fully characterized. In this report, we show that the mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in PGE 2 -induced colon cancer cell responses. Indeed, stimulation of LS174T cells with PGE 2 increased mTORC1 activity as observed by the augmentation of S6 ribosomal protein phosphorylation, a downstream effector of mTORC1. The PGE 2 EP 4 receptor was responsible for transducing the signal to mTORC1. Moreover, PGE 2 increased colon cancer cell proliferation as well as the growth of colon cancer cell colonies grown in matrigel and blocking mTORC1 by rapamycin or ATP-competitive inhibitors of mTOR abrogated these effects. Similarly, the inhibition of mTORC1 by downregulation of its component raptor using RNA interference blocked PGE 2 -induced LS174T cell growth. Finally, stimulation of LS174T cells with PGE 2 increased VEGF production which was also prevented by mTORC1 inhibition. Taken together, these results show that mTORC1 is an important signaling intermediary in PGE 2 mediated colon cancer cell growth and VEGF production. They further support a role for mTORC1 in inflammation induced tumor growth

Holmium-doped fluorotellurite microstructured fibers for 2.1 μm lasing.

Science.gov (United States)

Yao, Chuanfei; He, Chunfeng; Jia, Zhixu; Wang, Shunbin; Qin, Guanshi; Ohishi, Yasutake; Qin, Weiping

2015-10-15

Holmium (Ho3+)-doped fluorotellurite microstructured fibers based on TeO2-BaF2-Y2O3 glasses are fabricated by using a rod-in-tube method. By using a 1.992 μm fiber laser as the pump source, lasing at 2.077 μm is obtained from a 27 cm long Ho3+-doped fluorotellurite microstructured fiber. The maximum unsaturated power is about 161 mW and the corresponding slope efficiency is up to 67.4%. The influence of fiber length on lasing at 2.1 μm is also investigated. Our results show that Ho3+-doped fluorotellurite microstructured fibers are promising gain media for 2.1 μm laser applications.

Genetic counselling, BRCA1/2 status and clinico-pathologic characteristics of patients with ovarian cancer before 50 years of age

Directory of Open Access Journals (Sweden)

Cvelbar Mirjam

2017-05-01

Full Text Available In Slovenia like in other countries, till recently, personal history of epithelial ovarian cancer (EOC has not been included among indications for genetic counselling. Recent studies reported up to 17% rate of germinal BRCA1/2 mutation (gBRCA1/2m within the age group under 50 years at diagnosis. The original aim of this study was to invite to the genetic counselling still living patients with EOC under 45 years, to offer gBRCA1/2m testing and to perform analysis of gBRCA1/2m rate and of clinico-pathologic characteristics. Later, we added also the data of previously genetically tested patients with EOC aged 45 to 49 years.

WP2 Annual Report 1st year

DEFF Research Database (Denmark)

Jensen, Jørgen Juncher

2006-01-01

This report constitutes a contribution to the consolidated annual report covering the activities in SAFEDOR for the first year (1/2-2005 to 1/2-2006). The report deals in five separate chapters one for each of the five subprojects. The objectives of WP2 are • To develop and / or refine such advan...

Infinitely many N=1 dualities from m+1−m=1

Energy Technology Data Exchange (ETDEWEB)

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

2015-10-06

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

M-theory solutions invariant under D(2,1; γ) + D(2,1;γ)

Energy Technology Data Exchange (ETDEWEB)

Bachas, C. [Laboratoire de Physique Theorique de l' Ecole Normale Superieure Unite mixte (UMR 8549) du CNRS et de l' ENS, Paris (France); D' Hoker, E. [Department of Physics and Astronomy, University of California, Los Angeles, CA (United States); Estes, J. [Blackett Laboratory, Imperial College, London (United Kingdom); Krym, D. [Physics Department, New York City College of Technology, The City University of New York, Brooklyn, NY (United States)

2014-03-06

We simplify and extend the construction of half-BPS solutions to 11-dimensional supergravity, with isometry superalgebra D(2,1;γ) + D(2,1;γ). Their space-time has the form AdS{sub 3} x S{sup 3} x S{sup 3} warped over a Riemann surface Σ. It describes near-horizon geometries of M2 branes ending on, or intersecting with, M5 branes along a common string. The general solution to the BPS equations is specified by a reduced set of data (γ, h, G), where γ is the real parameter of the isometry superalgebra, and h and G are functions on Σ whose differential equations and regularity conditions depend only on the sign of γ. The magnitude of γ enters only through the map of h,G onto the supergravity fields, thereby promoting all solutions into families parametrized by vertical stroke γ vertical stroke. By analyzing the regularity conditions for the supergravity fields, we prove two general theorems: (i) that the only solution with a 2-dimensional CFT dual is AdS{sub 3} x S{sup 3} x S{sup 3} x R {sup 2}, modulo discrete identifications of the flat R {sup 2}, and (ii) that solutions with γ < 0 cannot have more than one asymptotic higher-dimensional AdS region. We classify the allowed singularities of h and G near the boundary of Σ, and identify four local solutions: asymptotic AdS{sub 4}/Z{sub 2} or AdS{sub 7}' regions; highly-curved M5-branes; and a coordinate singularity called the ''cap''. By putting these ''Lego'' pieces together we recover all known global regular solutions with the above symmetry, including the self-dual strings on M5 for γ <0, and the Janus solution for γ > 0, but now promoted to families parametrized by vertical stroke γ vertical stroke. We also construct exactly new regular solutions which are asymptotic to AdS{sub 4}/Z{sub 2} for γ < 0, and conjecture that they are a different superconformal limit of the self-dual string. Finally, we construct exactly γ > 0 solutions with highly curved M5

M2-F1 in flight over lakebed on tow line

Science.gov (United States)

1963-01-01

After initial ground-tow flights of the M2-F1 using the Pontiac as a tow vehicle, the way was clear to make air tows behind a C-47. The first air tow took place on 16 August 1963. Pilot Milt Thompson found that the M2-F1 flew well, with good control. This first flight lasted less than two minutes from tow-line release to touchdown. The descent rate was 4,000 feet per minute. The wingless, lifting body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved adequate for the roughly 400 car tows that got

Educational intervention to improve adherence to the Mediterranean diet among parents and their children aged 1-2 years. EniM clinical trial.

Science.gov (United States)

Roset-Salla, Margarita; Ramon-Cabot, Joana; Salabarnada-Torras, Jordi; Pera, Guillem; Dalmau, Albert

2016-04-01

The objective of the present study was to evaluate the effectiveness of an educational programme on healthy alimentation, carried out in day-care centres and aimed at the parents of children from 1 to 2 years of age, regarding the acquisition of healthy eating habits among themselves and their children. We performed a multicentre, multidisciplinary, randomized controlled study in a community setting. The EniM study (nutritional intervention study among children from Mataró) was performed in twelve day-care centres in Mataró (Spain). Centres were randomized into a control group (CG) and an intervention group (IG). IG received four or five educational workshops on diet, CG did not have workshops. Children, not exclusively breast-fed, from 1 to 2 years of age, in the participating day-care centres and the persons responsible for their alimentation (mother or father). Thirty-five per cent of the IG did not attend the minimum of three workshops and were excluded. The CG included seventy-four children and seventy-two parents and the IG seventy-five children and sixty-seven parents. Both groups were comparable at baseline. Basal adherence to the Mediterranean diet was 56·4 % in parents (Gerber index) and 7·7 points in children (Kidmed test). At 8 months, Mediterranean diet adherence had improved in the IG by 5·8 points in the Gerber index (P=0·01) and 0·6 points in the Kidmed test (P=0·02) compared with the CG. This educational intervention performed in parents at the key period of incorporation of a 1-2-year-old child to the family table showed significant increases in adherence of the parents to the Mediterranean diet, suggesting future improvement in different indicators of health and an expected influence on the diet of their children.

M2-F1 in flight during low-speed car tow

Science.gov (United States)

1963-01-01

The M2-F1 shown in flight during a low-speed car tow runs across the lakebed. Such tests allowed about two minutes to test the vehicle's handling in flight. NASA Flight Research Center (later redesignated the Dryden Flight Research Center) personnel conducted as many as 8 to 14 ground-tow flights in a single day either to test the vehicle in preparation for air tows or to train pilots to fly the vehicle before they undertook air tows. The wingless, lifting body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30

Conversion of tropical lowland forest reduces nutrient return through litterfall, and alters nutrient use efficiency and seasonality of net primary production.

Science.gov (United States)

Kotowska, Martyna M; Leuschner, Christoph; Triadiati, Triadiati; Hertel, Dietrich

2016-02-01

Tropical landscapes are not only rapidly transformed by ongoing land-use change, but are additionally confronted by increasing seasonal climate variation. There is an increasing demand for studies analyzing the effects and feedbacks on ecosystem functioning of large-scale conversions of tropical natural forest into intensively managed cash crop agriculture. We analyzed the seasonality of aboveground litterfall, fine root litter production, and aboveground woody biomass production (ANPP(woody)) in natural lowland forests, rubber agroforests under natural tree cover ("jungle rubber"), rubber and oil palm monocultures along a forest-to-agriculture transformation gradient in Sumatra. We hypothesized that the temporal fluctuation of litter production increases with increasing land-use intensity, while the associated nutrient fluxes and nutrient use efficiency (NUE) decrease. Indeed, the seasonal variation of aboveground litter production and ANPP(woody) increased from the natural forest to the plantations, while aboveground litterfall generally decreased. Nutrient return through aboveground litter was mostly highest in the natural forest; however, it was significantly lower only in rubber plantations. NUE of N, P and K was lowest in the oil palm plantations, with natural forest and the rubber systems showing comparably high values. Root litter production was generally lower than leaf litter production in all systems, while the root-to-leaf ratio of litter C flux increased along the land-use intensity gradient. Our results suggest that nutrient and C cycles are more directly affected by climate seasonality in species-poor agricultural systems than in species-rich forests, and therefore might be more susceptible to inter-annual climate fluctuation and climate change.

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

Science.gov (United States)

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

2018-06-01

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

Crystal structures of the 2:2 complex of 1,1′-(1,2-phenylenebis(3-m-tolylurea and tetrabutylammonium chloride or bromide

Directory of Open Access Journals (Sweden)

Chao Huang

2017-09-01

Full Text Available The title compounds, tetrabutylammonium chloride–1,1′-(1,2-phenylenebis(3-m-tolylurea (1/1, C16H36N+·Cl−·C22H22N4O2 or [(n-Bu4N+·Cl−(C22H22N4O2] (I and tetrabutylammonium bromide–1,1′-(1,2-phenylenebis(3-m-tolylurea (1/1, C16H36N+·Br−·C22H22N4O2 or [(n-Bu4N+·Br−(C22H22N4O2] (II, both comprise a tetrabutylammonium cation, a halide anion and an ortho-phenylene bis-urea molecule. Each halide ion shows four N—H...X (X = Cl or Br interactions with two urea receptor sites of different bis-urea moieties. A crystallographic inversion centre leads to the formation of a 2:2 arrangement of two halide anions and two bis-urea molecules. In the crystals, the dihedral angle between the two urea groups of the bis-urea molecule in (I [defined by the four N atoms, 165.4 (2°] is slightly smaller than that in (II [167.4 (2°], which is probably due to the smaller ionic radius of chloride compared to bromide.

Manganese biogeochemistry in a central Czech Republic catchment

Science.gov (United States)

Navratil, T.; Shanley, J.B.; Skrivan, P.; Kram, P.; Mihaljevic, M.; Drahota, P.

2007-01-01

Mn biogeochemistry was studied from 1994 to 2003 in a small forested catchment in the central Czech Republic using the watershed mass balance approach together with measurements of internal stores and fluxes. Mn inputs in bulk deposition were relatively constant during a period of sharply decreasing acidic deposition, suggesting that the Mn source was terrestrial, and not from fossil fuel combustion. Mn inputs in bulk deposition and Mn supplied by weathering each averaged 13 mg m-2 year-1 (26 mg m -2 year-1 total input), whereas Mn export in streamwater and groundwater averaged 43 mg m-2 year-1. Thus an additional Mn source is needed to account for 17 mg m-2 year -1. Internal fluxes and pools of Mn were significantly greater than annual inputs and outputs. Throughfall Mn flux was 70 mg m-2 year-1, litterfall Mn flux was 103 mg m-2 year -1, and Mn net uptake by vegetation was 62 mg m-2 year-1. Large pools of labile or potentially labile Mn were present in biomass and surficial soil horizons. Small leakages from these large pools likely supply the additional Mn needed to close the watershed mass balance. This leakage may reflect an adjustment of the ecosystem to recent changes in atmospheric acidity. ?? 2007 Springer Science+Business Media B.V.

Genetic Counselling, BRCA1/2 Status and Clinico-pathologic Characteristics of Patients with Ovarian Cancer before 50 Years of Age

Science.gov (United States)

Cvelbar, Mirjam; Hocevar, Marko; Novakovic, Srdjan; Stegel, Vida; Perhavec, Andraz

2017-01-01

Abstract Background In Slovenia like in other countries, till recently, personal history of epithelial ovarian cancer (EOC) has not been included among indications for genetic counselling. Recent studies reported up to 17% rate of germinal BRCA1/2 mutation (gBRCA1/2m) within the age group under 50 years at diagnosis. The original aim of this study was to invite to the genetic counselling still living patients with EOC under 45 years, to offer gBRCA1/2m testing and to perform analysis of gBRCA1/2m rate and of clinico-pathologic characteristics. Later, we added also the data of previously genetically tested patients with EOC aged 45 to 49 years. Patients and methods All clinical data have to be interpreted in the light of many changes happened in the field of EOC just in the last few years: new hystology stage classification (FIGO), new hystology types and differentiation grades classification, new therapeutic possibilities (PARP inhibitors available, also in Slovenia) and new guidelines for genetic counselling of EOC patients (National Comprehensive Cancer Network, NCCN), together with next-generation sequencing possibilities. Results Compliance rate at the invitation was 43.1%. In the group of 27 invited or previously tested patients with EOC diagnosed before the age of 45 years, five gBRCA1/2 mutations were found. The gBRCA1/2m detection rate within the group was 18.5%. There were 4 gBRCA1 and 1 gBRCA2 mutations detected. In the extended group of 42 tested patients with EOC diagnosed before the age of 50 years, 14 gBRCA1/2 mutations were found. The gBRCA1/2m detection rate within this extended, partially selected group was 33.3%. There were 11 gBRCA1 and 3 gBRCA2 mutations detected. Conclusions The rate of gBRCA1/2 mutation in tested unselected EOC patients under the age of 50 years was higher than 10%, namely 18.5%. Considering also a direct therapeuthic benefit of PARP inhibitors for BRCA positive patients, there is a double reason to offer genetic testing to

Calculation of parity violating effects in the 62P/sub 1/2/-72P/sub 1/2/ forbidden M1 transition in thallium

International Nuclear Information System (INIS)

Neuffer, D.B.

1977-05-01

Calculations are presented of the E1 amplitude expected in forbidden M1 transitions of Tl and Cs if parity is violated in the neutral weak e-N interaction, as proposed in a number of gauge models, including that of Weinberg and Salam. Valence electron wave functions are generated as numerical solutions to the Dirac equation in a modified Tietz central potential. These wave functions are used to calculate allowed E1 transition rates, hfs splittings, and Stark E1 transition ampitudes. These results are compared with experiment and the agreement is generally good. The relativistic Tl 6 2 P/sub 1/2/-7 2 P/sub 1/2/ M1 transition amplitude M is also calculated, and corrections due to interconfiguration interaction, Breit interaction, and hfs mixing are included. The parity violating E1 amplitude E/sub PV/ is calculated and a value for the circular dichroism in the Weinberg model delta = -2.6 x 10 -3 is obtained. Parity violating effects in other Tl transitions are discussed. Contributions to the M1 amplitude for the forbidden Cs 6 2 S/sub 1/2/-7 2 S/sub 1/2/ and 6 2 S/sub 1/2/-8 2 S/sub 1/2/ transitions and to the Cs 6 2 S/sub 1/2/ g-factor anomaly from relativistic effects, Breit interaction, interconfiguration interaction, and hfs mixing are calculated, and it is found that this current theoretical description is not entirely adequate. The parity violating E1 amplitude E/sub PV/ for the 6S/sub 1/2/-7 2 S/sub 1/2/ and 6S/sub 1/2/-8 2 S/sub 1/2/ transitions is evaluated. With a measured value M/sub expt/ and the Weinberg value Q/sub W/ = -99, a circular dichroism delta = 1.64 x 10 -4 for the 6 2 S/sub 1/2/-7 2 S/sub 1/2/ transition is found

PGE{sub 2}-induced colon cancer growth is mediated by mTORC1

Energy Technology Data Exchange (ETDEWEB)

Dufour, Marc, E-mail: Marc.dufour@chuv.ch; Faes, Seraina, E-mail: Seraina.faes@chuv.ch; Dormond-Meuwly, Anne, E-mail: Anne.meuwly-Dormond@chuv.ch; Demartines, Nicolas, E-mail: Demartines@chuv.ch; Dormond, Olivier, E-mail: Olivier.dormond@chuv.ch

2014-09-05

Highlights: • PGE{sub 2} activates mTORC1 in colon cancer cells. • Inhibition of mTORC1 blocks PGE{sub 2} induced colon cancer cell growth. • mTORC1 is a signaling intermediary in PGE{sub 2} induced colon cancer cell responses. - Abstract: The inflammatory prostaglandin E{sub 2} (PGE{sub 2}) cytokine plays a key role in the development of colon cancer. Several studies have shown that PGE{sub 2} directly induces the growth of colon cancer cells and furthermore promotes tumor angiogenesis by increasing the production of the vascular endothelial growth factor (VEGF). The signaling intermediaries implicated in these processes have however not been fully characterized. In this report, we show that the mechanistic target of rapamycin complex 1 (mTORC1) plays an important role in PGE{sub 2}-induced colon cancer cell responses. Indeed, stimulation of LS174T cells with PGE{sub 2} increased mTORC1 activity as observed by the augmentation of S6 ribosomal protein phosphorylation, a downstream effector of mTORC1. The PGE{sub 2} EP{sub 4} receptor was responsible for transducing the signal to mTORC1. Moreover, PGE{sub 2} increased colon cancer cell proliferation as well as the growth of colon cancer cell colonies grown in matrigel and blocking mTORC1 by rapamycin or ATP-competitive inhibitors of mTOR abrogated these effects. Similarly, the inhibition of mTORC1 by downregulation of its component raptor using RNA interference blocked PGE{sub 2}-induced LS174T cell growth. Finally, stimulation of LS174T cells with PGE{sub 2} increased VEGF production which was also prevented by mTORC1 inhibition. Taken together, these results show that mTORC1 is an important signaling intermediary in PGE{sub 2} mediated colon cancer cell growth and VEGF production. They further support a role for mTORC1 in inflammation induced tumor growth.

Inflammation induced mTORC2-Akt-mTORC1 signaling promotes macrophage foam cell formation.

Science.gov (United States)

Banerjee, Dipanjan; Sinha, Archana; Saikia, Sudeshna; Gogoi, Bhaskarjyoti; Rathore, Arvind K; Das, Anindhya Sundar; Pal, Durba; Buragohain, Alak K; Dasgupta, Suman

2018-06-05

The transformation of macrophages into lipid loaded foam cells is a critical and early event in the pathogenesis of atherosclerosis. Several recent reports highlighted that induction of TLR4 signaling promotes macrophage foam cell formation; however, the underlying molecular mechanisms have not been clearly elucidated. Here, we found that the TLR4 mediated inflammatory signaling communicated with mTORC2-Akt-mTORC1 metabolic cascade in macrophage and thereby promoting lipid uptake and foam cell formation. Mechanistically, LPS treatment markedly upregulates TLR4 mediated inflammatory pathway which by activating mTORC2 induces Akt phosphorylation at serine 473 and that aggravate mTORC1 dependent scavenger receptors expression and consequent lipid accumulation in THP-1 macrophages. Inhibition of mTORC2 either by silencing Rictor expression or inhibiting its association with mTOR notably prevents LPS induced Akt activation, scavenger receptors expression and macrophage lipid accumulation. Although suppression of mTORC1 expression by genetic knockdown of Raptor did not produce any significant change in Akt S473 phosphorylation, however, incubation with Akt activator in Rictor silenced cells failed to promote scavenger receptors expression and macrophage foam cell formation. Thus, present research explored the signaling pathway involved in inflammation induced macrophage foam cells formation and therefore, targeting this pathway might be useful for preventing macrophage foam cell formation. Copyright © 2018 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

Synthesis of Poly(m-pyridylene-1,2-diphenylvinylene

Directory of Open Access Journals (Sweden)

Rosana S. Montani

2000-03-01

Full Text Available The synthesis by dehalogenating polycondensation and characterization of a new soluble conjugated polymer, poly(m-pyridylene-1,2-diphenylvinylene, DP-PPyV, is reported here. It shows good mechanical properties and a λmax = 330 nm. The maximum intensity peak of MALDI-TOF corresponds to 1.800 Da.

Geometry and bonding in the ground and lowest triplet state of D{sub 6h} symmetric crenellated edged C{sub 6[3m(m-1)+1]}H{sub 6(2m-1)} (m = 2,..., 6) graphene hydrocarbon molecules

Energy Technology Data Exchange (ETDEWEB)

Philpott, Michael R., E-mail: philpott@imr.edu [Center for Computational Materials Science, Institute of Materials Science, Tohoku University, 2-1-1 Katahira, Aoba-ku, 980-8577 Sendai (Japan); Kawazoe, Yoshiyuki [Center for Computational Materials Science, Institute of Materials Science, Tohoku University, 2-1-1 Katahira, Aoba-ku, 980-8577 Sendai (Japan)

2009-03-30

Ab initio plane wave all valence electron based DFT calculations were used to explore the dichotomy of perimeter vs. interior in the electronic and geometric structure of the D{sub 6h} singlet ground state and D{sub 2h} lowest triplet state of planar graphene hydrocarbon molecules with crenellated (arm chair) edges and the general formula C{sub 6[3m(m-1)+1]} H{sub 6(2m-1)} where m = 2,...,6. The largest molecule C{sub 546}H{sub 66} was 4.78 nm across and contained 2250 valence electrons. These molecules are nominally 'fully benzenoid hydrocarbons'. However with increasing size, the core of central atoms abandoned any fully benzenoid geometry they had in small systems and organized into single layer graphite (graphene) structure. The perimeter atoms of the crenellation adopted a conjugated geometry with unequal bonds and between core and perimeter there were some C{sub 6} rings retaining remnants of aromatic sextet-type properties. Compared to a zigzag edge the crenellated edge conferred stability in all the systems studied as measured by the singlet homo-lumo level gap BG{sub 0} and the singlet-lowest triplet energy gap {Delta}E{sub ST}. For the largest crenellated system (m = 6) BG{sub 0} and {Delta}E{sub ST} were approximately 0.7 eV, larger in value than for similarly sized hexagonal graphenes with zigzag edges. Triplet states were identified for all the molecules in the series and in the case of the m = 2 molecule hexabenzocoronene C{sub 42}H{sub 18}, two conformations with D{sub 2h} symmetry were identified and compared to features on the triplet state potential energy surface of benzene.

Agomelatine or ramelteon as treatment adjuncts in glioblastoma and other M1- or M2-expressing cancers.

Science.gov (United States)

Kast, Richard E

2015-01-01

The impressive but sad list of over forty clinical studies using various cytotoxic chemotherapies published in the last few years has failed to increase median survival of glioblastoma beyond two years after diagnosis. In view of this apparent brick wall, adjunctive non-cytotoxic growth factor blocking drugs are being tried, as in the CUSP9* protocol. A related theme is searching for agonists at growth inhibiting receptors. One such dataset is that of melatonin agonism at M1 or M2 receptors found on glioblastoma cells, being a negative regulator of these cells' growth. Melatonin itself is an endogenous hormone, but when used as an exogenously administered drug it has many disadvantages. Agomelatine, marketed as an antidepressant, and ramelteon, marketed as a treatment for insomnia, are currently-available melatonin receptor agonists. These melatonin receptor agonists have significant advantages over the natural ligand: longer half-life, better oral absorption, and higher affinity to melatonin receptors. They have an eminently benign side effect profile. As full agonists they should function to inhibit glioblastoma growth, as demonstrated for melatonin. A potentially helpful ancillary attribute of melatonergic agonists in glioblastoma treatment is an increase in interleukin-2 synthesis, expected, at least partially, to reverse some of the immunosuppression associated with glioblastoma.

Investigation into the dehydration of selenate doped Na2M(SO4)2·2H2O (M = Mn, Fe, Co and Ni): Stabilisation of the high Na content alluaudite phases Na3M1.5(SO4)3-1.5x(SeO4)1.5x (M = Mn, Co and Ni) through selenate incorporation

Science.gov (United States)

Driscoll, L. L.; Kendrick, E.; Knight, K. S.; Wright, A. J.; Slater, P. R.

2018-02-01

In this paper we report an investigation into the phases formed on dehydration of Na2M(SO4)2-x(SeO4)x·2H2O (0 ≤ x ≤ 1; M = Mn, Fe, Co and Ni). For the Fe series, all attempts to dehydrate the samples doped with selenate resulted in amorphous products, and it is suspected that a side redox reaction involving the Fe and selenate may be occurring leading to phase decomposition and hence the lack of a crystalline product on dehydration. For M = Mn, Co, Ni, the structure observed was shown to depend upon the transition metal cation and level of selenate doping. An alluaudite phase, Na3M1.5(SO4)3-1.5x(SeO4)1.5x, was observed for the selenate doped compositions, with this phase forming as a single phase for x ≥ 0.5 M = Co, and x = 1.0 M = Ni. For M = Mn, the alluaudite structure is obtained across the series, albeit with small impurities for lower selenate content samples. Although the alluaudite-type phases Na2+2y(Mn/Co)2-y(SO4)3 have recently been reported [1,2], doping with selenate appears to increase the maximum sodium content within the structure. Moreover, the selenate doped Ni based samples reported here are the first examples of a Ni sulfate/selenate containing system exhibiting the alluaudite structure.

Thermodynamic properties of the solid solutions CuCr/sub 2/S/sub 4/ in Cu/sub 1///sub 2/M/sub 1///sub 2/Cr/sub 2/S/sub 4/ (M=Ga, In)

Energy Technology Data Exchange (ETDEWEB)

Titov, V.V.; Gordeev, I.V.; Kesler, Y.A.; Shchelkotunov, V.A.; Tret' yakov, Y.D.

1985-09-01

Using an adiabatic calorimeter and a quartz dilatometer, the temperature dependences of the heat capacity for the solid solutions CuCr/sub 2/S/sub 4/ in Cu/sub 1///sub 2/M/sub 1///sub 2/Cr/sub 2/S/sub 4/ (M - Ga, In) were determined, the different components of the heat capacity were evaluated, and the thermodynamic parameters of the magnetic transformation were calculated.

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

NARCIS (Netherlands)

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

1986-01-01

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

M2-F1 in flight being towed by a C-47

Science.gov (United States)

1964-01-01

The M2-F1 Lifting Body is seen here being towed behind a C-47 at the Flight Research Center (later redesignated the Dryden Flight Research Center), Edwards, California. In this rear view, the M2-F1 is flying above and to one side of the C-47. This was done to avoid wake turbulence from the towplane. Lacking wings, the M2-F1 used an unusual configuration for its control surfaces. It had two rudders on the fins, two elevons (called 'elephant ears') mounted on the outsides of the fins, and two body flaps on the upper rear fuselage. The wingless, lifting body aircraft design was initially concieved as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. These initial tests produced enough flight data about the M2-F1 to proceed with flights behind the C-47 tow plane at greater altitudes. The C-47 took the craft to an altitude of 12,000 where free flights back to Rogers Dry Lake began. Pilot for the first series of flights of the M2-F1 was NASA research pilot Milt Thompson. Typical glide flights with the M2-F1 lasted about two minutes and reached speeds of 110 to l20 mph. More than 400 ground tows and 77 aircraft tow flights were carried out with the M2-F1. The success of Dryden's M2-F1 program led to NASA's development and construction of two heavyweight lifting bodies based on studies at NASA's Ames and

Cyclic AMP is a key regulator of M1 to M2a phenotypic conversion of microglia in the presence of Th2 cytokines.

Science.gov (United States)

Ghosh, Mousumi; Xu, Yong; Pearse, Damien D

2016-01-13

Microglia and macrophages play a central role in neuroinflammation. Pro-inflammatory cytokines trigger their conversion to a classically activated (M1) phenotype, sustaining inflammation and producing a cytotoxic environment. Conversely, anti-inflammatory cytokines polarize the cells towards an alternatively activated (M2), tissue reparative phenotype. Elucidation of the signal transduction pathways involved in M1 to M2 phenotypic conversion may provide insight into how the innate immune response can be harnessed during distinct phases of disease or injury to mediate neuroprotection and neurorepair. Microglial cells (cell line and primary) were subjected to combined cyclic adenosine monophosphate (cyclic AMP) and IL-4, or either alone, in the presence of pro-inflammatory mediators, lipopolysaccharide (LPS), or tumor necrosis factor-α (TNF-α). Their effects on the expression of characteristic markers for M1 and M2 microglia were assessed. Similarly, the M1 and M2 phenotypes of microglia and macrophages within the lesion site were then evaluated following a contusive spinal cord injury (SCI) to the thoracic (T8) spinal cord of rats and mice when the agents were administered systemically. It was demonstrated that cyclic AMP functions synergistically with IL-4 to promote M1 to M2 conversion of microglia in culture. The combination of cyclic AMP and IL-4, but neither alone, induced an Arg-1(+)/iNOS(-)cell phenotype with concomitant expression of other M2-specific markers including TG2 and RELM-α. M2-converted microglia showed ameliorated production of pro-inflammatory cytokines (TNF-α and IP-10) and reactive oxygen species, with no alteration in phagocytic properties. M2a conversion required protein kinase A (PKA), but not the exchange protein directly activated by cyclic AMP (EPAC). Systemic delivery of cyclic AMP and IL-4 after experimental SCI also promoted a significant M1 to M2a phenotypic change in microglia and macrophage population dynamics in the lesion

Temperature-dependent Raman and ultraviolet photoelectron spectroscopy studies on phase transition behavior of VO{sub 2} films with M1 and M2 phases

Energy Technology Data Exchange (ETDEWEB)

Okimura, Kunio, E-mail: okifn@keyaki.cc.u-tokai.ac.jp; Hanis Azhan, Nurul [Graduate School of Engineering, Tokai University, Hiratsuka 259-1292 (Japan); Hajiri, Tetsuya [UVSOR Facility, Institute for Molecular Science, Okazaki 444-8585 (Japan); Graduate School of Engineering, Nagoya University, Nagoya 464-8603 (Japan); Kimura, Shin-ichi [UVSOR Facility, Institute for Molecular Science, Okazaki 444-8585 (Japan); Graduate School of Frontier Biosciences, Osaka University, Suita 565-0871 (Japan); Zaghrioui, Mustapha; Sakai, Joe [GREMAN, UMR 7347 CNRS, Université François Rabelais de Tours, Parc de Grandmont, 37200 Tours (France)

2014-04-21

Structural and electronic phase transitions behavior of two polycrystalline VO{sub 2} films, one with pure M1 phase and the other with pure M2 phase at room temperature, were investigated by temperature-controlled Raman spectroscopy and ultraviolet photoelectron spectroscopy (UPS). We observed characteristic transient dynamics in which the Raman modes at 195 cm{sup −1} (V-V vibration) and 616 cm{sup −1} (V-O vibration) showed remarkable hardening along the temperature in M1 phase film, indicating the rearrangements of V-V pairs and VO{sub 6} octahedra. It was also shown that the M1 Raman mode frequency approached those of invariant M2 peaks before entering rutile phase. In UPS spectra with high energy resolution of 0.03 eV for the M2 phase film, narrower V{sub 3d} band was observed together with smaller gap compared to those of M1 phase film, supporting the nature of Mott insulator of M2 phase even in the polycrystalline film. Cooperative behavior of lattice rearrangements and electronic phase transition was suggested for M1 phase film.

Benefit of adjuvant chemotherapy after resection of stage II (T1-2N1M0) non-small cell lung cancer in elderly patients.

Science.gov (United States)

Berry, Mark F; Coleman, Brooke K; Curtis, Lesley H; Worni, Mathias; D'Amico, Thomas A; Akushevich, Igor

2015-02-01

We evaluated the use and efficacy of adjuvant chemotherapy after resection of T1-2N1M0 non-small cell lung cancer (NSCLC) in elderly patients. Factors associated with the use of adjuvant chemotherapy in patients older than 65 years of age who underwent surgical resection of T1-2N1M0 NSCLC without induction chemotherapy or radiation in the Surveillance, Epidemiology, and End Results-Medicare database from 1992 to 2006 were assessed using a multivariable logistic regression model that included treatment, patient, tumor, and census tract characteristics. Overall survival (OS) was analyzed using the Kaplan-Meier approach and inverse probability weight-adjusted Cox proportional hazard models. Overall, 2,781 patients who underwent surgical resection as the initial treatment for T1-2N1M0 NSCLC and survived at least 31 days after surgery were identified, with adjuvant chemotherapy given to 784 patients (28.2 %). Factors that predicted adjuvant chemotherapy use were younger age and higher T status. The 5-year OS was significantly better for patients who received adjuvant chemotherapy compared with patients not given adjuvant chemotherapy: 35.8 % (95 % confidence interval [CI] 31.9-39.6) vs. 28.0 % (95 % CI 25.9-30.0) (p = 0.008). In the inverse probability weight-adjusted Cox proportional hazard regression model, adjuvant chemotherapy use predicted significantly improved survival (hazard ratio 0.84; 95 % CI 0.76-0.92; p = 0.0002). Adjuvant chemotherapy after resection of T1-2N1M0 NSCLC is associated with significantly improved survival in patients older than 65 years. These data can be used to provide elderly patients with realistic expectations of the potential benefits when considering adjuvant chemotherapy in this setting.

Organic matter budget in a mixed-hardwood forest in north central Florida

International Nuclear Information System (INIS)

Lugo, A.E.; Gamble, J.F.; Ewel, K.C.

1978-01-01

Organic-matter flows through a mixed-hardwood forest were analyzed as part of a study of the unusual behavior of 137 Cs in Florida ecosystems. The data suggest that rates of organic-matter flow in the mixed-hardwood forest in north central Florida more closely approach those of similar systems in tropical areas than in temperate areas. Annual litterfall was 1069 g/m 2 ; litter turnover, 1.3/year; net daytime productivity of leaves and twigs, 12.4 g m -2 day -1 ; nighttime respiration, 5.1 g m -2 day -1 ; and stem respiration, 1.4 g m -2 day -1 . Constancy of litter storage (820 g/m 2 ) and leaf fall and lack of net wood deposition indicate that the forest is in steady state. It was concluded that 137 Cs accumulation in this forest is probably caused by intrinsic ecosystem processes, as previously suggested, rather than by buildup that might be expected in a successional ecosystem

Positronium formation and hydrated positron reactions in H2O, D2O, 1.74 M PPS/H2O and 1.74 M PPS/D2O solutions of Cl−, Br− and I−

DEFF Research Database (Denmark)

Mogensen, O. E.; Pedersen, Niels Jørgen

1986-01-01

Angular correlation of annihilation photons were measured for H2O, D2O, 1.74 M PPS/H2O and 1.74 M PPS/D2O solutions of Cl−, Br− and I−. The three components of the angular correlation spectra for D2O and H2O were nearly identical in shape. The positronium (Ps) yields for the H2O and D2O solutions...... before annihilation (lifetime 400 ps) was determined for the three halides in the four solvents. Simple kinetic equations (“trapping model”) with time dependent rate constant, solved analytically, could explain the [X−, e+] formation in H2O fairly well for concentrations below 0.03 M X−, if a diffusion...... controlled reaction with positron diffusion constant D = 5 × 10−5 cm2/s and reaction radius R = 1 nm were assumed. The three halides gave roughly identical [X−, e+] formation below 0.03 M X−. The difference between the four solutions could be explained partly only in terms of viscosity change for the model...

The structural, electronic, magnetic, and mechanical properties of perovskite oxides PbM1/2Nb1/2O3 (M = Fe, Co and Ni)

Science.gov (United States)

Erkisi, A.; Surucu, G.; Deligoz, E.

2018-03-01

In this study, the structural, electronic, magnetic, and mechanical properties of perovskite oxides PbM1/2Nb1/2O3 (M = Fe, Co and Ni) are investigated. The systems are treated in ferromagnetic order. The calculations are carried out in the framework of density functional theory (DFT) within the plane-wave pseudopotential method. The exchange-correlation potential is approximated by generalized-gradient spin approach (GGA). The intra-atomic Coulomb repulsion is also taken into account in calculations (GGA + U). We have considered two generalized-gradient spin approximation functionals, which are Perdew-Burke-Ernzerhof (PBE) and PBE for solids (PBEsol) for structural parameter calculations when it included Hubbard potential. Although the spin-polarized electronic band structures of PbCo1/2Nb1/2O3 and PbNi1/2Nb1/2O3 systems exhibit metallic property in ferromagnetic phase, a bandgap is observed in spin-down states of PbFe1/2Nb1/2O3 resulting in half-metallic behavior. The main reason for this behavior is attributed to the hybridization between d-states of transition metal atoms and p-states of oxygen atoms. The stability mechanically and the calculated mechanical properties by using elastic constants show that these compounds are mechanically stable in tetragonal phase and have anisotropic character mechanically.

Litterfall, precipitation and nutrient fluxes in a secondary lowland rain forest in Ile-Ife, Nigeria Queda de serrapilheira, precipitação e fluxo de nutrientes em uma floresta pluvial secundária de terras baixas em Il-Ife, Nigéria

Directory of Open Access Journals (Sweden)

Modupe B. Oziegbe

2011-09-01

Full Text Available Litterfall, precipitation and nutrient fluxes were investigated in a 0.25 ha plot of a secondary lowland rain forest in Ile-Ife, Nigeria, for a period of one year. The study determined the magnitude of nutrient fluxes through (litterfall, incident rainfall, throughfall and stemflow and evaluated the relative importance of these components as pathways of nutrient transport to the soil of this forest. There was a significant monthly variation in litterfall and the highest values of the standing crop of litter occurred from November to March. The concentration of elements in both throughfall and stemflow were higher than those of incidence rainfall. Greater quantities of calcium, magnesium, iron, zinc, copper and nitrogen were deposited annually from the forest floor while greater quantities of mercury, potassium, sodium, phosphorus, lead and sulphur were deposited via precipitation. There was net leaching of all elements from the canopy as precipitation pass through it with the exception of copper, hydrogen ions and lead, which were retained in the canopy. The finding of this study shows that litterfall is the major pathway for the cycling of calcium, magnesium, nitrogen and all micronutrients investigated. Net precipitation is the major pathway for the cycling of potassium, phosphorus, sulphur and trace toxic metals (mercury and lead in the forest.Produção de serapilheira, precipitação e o fluxo de nutrientes foram investigados em uma parcela de 0,25 ha de uma floresta pluvial secundária de terras baixas em Ile-Ife, Nigéria, por um período de um ano. O estudo determinou a magnitude dos fluxos de nutrientes através da serrapilheira, da chuva incidente, da interceptada, da escoada pelo tronco, e também avaliou a importância relativa desses componentes como vias de transporte de nutrientes para o solo desta floresta. Houve variação mensal significativa na produção e acúmulo de serapilheira com maiores valores ocorrendo de novembro a

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

Science.gov (United States)

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

2016-06-01

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

An N=1 superfield action for M2 branes

International Nuclear Information System (INIS)

Mauri, Andrea; Petkou, Anastasios C.

2008-01-01

We present an octonionic N=1 superfield action that reproduces in components the action of Bagger and Lambert for M2 branes. By giving an expectation value to one of the scalars we obtain the maximally supersymmetric superfield action for D2 branes

Bone marrow-derived and peritoneal macrophages have different inflammatory response to oxLDL and M1/M2 marker expression

DEFF Research Database (Denmark)

Bisgaard, Line S; Mogensen, Christina K; Rosendahl, Alexander

2016-01-01

Macrophages are heterogeneous and can polarize into specific subsets, e.g. pro-inflammatory M1-like and re-modelling M2-like macrophages. To determine if peritoneal macrophages (PEMs) or bone marrow derived macrophages (BMDMs) resembled aortic macrophages from ApoE-/- mice, their M1/M2 phenotype,......, ACSL1, SRB1, DGAT1, and cpt1a) was decreased in advanced versus early lesions. In conclusion, PEMs and BMDMs are phenotypically distinct and differ from macrophages in lesions with respect to expression of M1/M2 markers and lipid metabolism genes....

Phosphorylation of Human Metapneumovirus M2-1 Protein Upregulates Viral Replication and Pathogenesis.

Science.gov (United States)

Cai, Hui; Zhang, Yu; Lu, Mijia; Liang, Xueya; Jennings, Ryan; Niewiesk, Stefan; Li, Jianrong

2016-08-15

Human metapneumovirus (hMPV) is a major causative agent of upper- and lower-respiratory-tract infections in infants, the elderly, and immunocompromised individuals worldwide. Like all pneumoviruses, hMPV encodes the zinc binding protein M2-1, which plays important regulatory roles in RNA synthesis. The M2-1 protein is phosphorylated, but the specific role(s) of the phosphorylation in viral replication and pathogenesis remains unknown. In this study, we found that hMPV M2-1 is phosphorylated at amino acid residues S57 and S60. Subsequent mutagenesis found that phosphorylation is not essential for zinc binding activity and oligomerization, whereas inhibition of zinc binding activity abolished the phosphorylation and oligomerization of the M2-1 protein. Using a reverse genetics system, recombinant hMPVs (rhMPVs) lacking either one or both phosphorylation sites in the M2-1 protein were recovered. These recombinant viruses had a significant decrease in both genomic RNA replication and mRNA transcription. In addition, these recombinant viruses were highly attenuated in cell culture and cotton rats. Importantly, rhMPVs lacking phosphorylation in the M2-1 protein triggered high levels of neutralizing antibody and provided complete protection against challenge with wild-type hMPV. Collectively, these data demonstrated that phosphorylation of the M2-1 protein upregulates hMPV RNA synthesis, replication, and pathogenesis in vivo The pneumoviruses include many important human and animal pathogens, such as human respiratory syncytial virus (hRSV), hMPV, bovine RSV, and avian metapneumovirus (aMPV). Among these viruses, hRSV and hMPV are the leading causes of acute respiratory tract infection in infants and children. Currently, there is no antiviral or vaccine to combat these diseases. All known pneumoviruses encode a zinc binding protein, M2-1, which is a transcriptional antitermination factor. In this work, we found that phosphorylation of M2-1 is essential for virus

Why is the neutrino oscillation formula expanded in Δm_2_1"2/Δm_3_1"2 still accurate near the solar resonance in matter?

International Nuclear Information System (INIS)

Xu, Xun-Jie

2015-01-01

The conventional approximate formula for neutrino oscillation in matter which is obtained from the expansion in terms of the ratio of mass square differences α=Δm_2_1"2/Δm_3_1"2≈0.03, first proposed by Cervera, et al. and Freund, turns out to be an accurate formula for accelerator neutrino experiments. Originally it required the neutrino energy to be well above the solar resonance to validate the expansion but it is found to be still very accurate when the formula is extrapolated to the resonance, which is practically important for the T2K experiment. This paper shows that the accuracy is guaranteed by cancellations of branch cut singularities and also, for the first time, analytically computes the actual error of the formula. The actual error implies that the original requirement can be safely removed in current experiments.

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

Science.gov (United States)

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

2016-01-01

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

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

Directory of Open Access Journals (Sweden)

Laura Dugo

2017-01-01

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

NFBD1/MDC1 participates in the regulation of G2/M transition in mammalian cells

International Nuclear Information System (INIS)

Bu, Youquan; Suenaga, Yusuke; Okoshi, Rintaro; Sang, Meixiang; Kubo, Natsumi; Song, Fangzhou; Nakagawara, Akira; Ozaki, Toshinori

2010-01-01

NFBD1/MDC1 is a large nuclear protein involved in the early cellular response to DNA damage. Upon DNA damage, NFBD1 has an ability to facilitate the efficient DNA repair. In the present study, we have found that, in addition to DNA damage response, NFBD1 plays a critical role in the regulation of G2/M transition. Expression study using synchronized HeLa cells demonstrated that, like the mitotic kinase Plk1, NFBD1 expression level is maximal in G2/M-phase of the cell cycle. siRNA-mediated knockdown of NFBD1 resulted in G2/M arrest as well as simultaneous apoptosis in association with a significant increase in the amounts of γH2AX and pro-apoptotic p73. Since a remarkable down-regulation of mitotic phospho-histone H3 was detectable in NFBD1-knocked down cells, it is likely that knocking down of NFBD1 inhibits G2/M transition. Taken together, our present findings suggest that NFBD1 has a pivotal role in the regulation of proper mitotic entry.

Dual inhibition of mTORC1 and mTORC2 perturbs cytoskeletal organization and impairs endothelial cell elongation.

Science.gov (United States)

Tsuji-Tamura, Kiyomi; Ogawa, Minetaro

2018-02-26

Elongation of endothelial cells is an important process in vascular formation and is expected to be a therapeutic target for inhibiting tumor angiogenesis. We have previously demonstrated that inhibition of mTORC1 and mTORC2 impaired endothelial cell elongation, although the mechanism has not been well defined. In this study, we analyzed the effects of the mTORC1-specific inhibitor everolimus and the mTORC1/mTORC2 dual inhibitor KU0063794 on the cytoskeletal organization and morphology of endothelial cell lines. While both inhibitors equally inhibited cell proliferation, KU0063794 specifically caused abnormal accumulation of F-actin and disordered distribution of microtubules, thereby markedly impairing endothelial cell elongation and tube formation. The effects of KU0063794 were phenocopied by paclitaxel treatment, suggesting that KU0063794 might impair endothelial cell morphology through over-stabilization of microtubules. Although mTORC1 is a key signaling molecule in cell proliferation and has been considered a target for preventing angiogenesis, mTORC1 inhibitors have not been sufficient to suppress angiogenesis. Our results suggest that mTORC1/mTORC2 dual inhibition is more effective for anti-angiogenic therapy, as it impairs not only endothelial cell proliferation, but also endothelial cell elongation. Copyright © 2018 Elsevier Inc. All rights reserved.

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

Directory of Open Access Journals (Sweden)

Al Shaimaa Hasan

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

Evaluation excitation functions for "2"8Si(n,p)"2"8Al, "3"1P(n,p)"3"1Si, and "1"1"3In(n,γ)"1"1"4"mIn reactions

International Nuclear Information System (INIS)

Zolotarev, K.I.

2014-10-01

Cross section data for "2"8Si(n,p)"2"8Al, "3"1P(n,p)"3"1Si and "1"1"3In(n,γ)"1"1"4"mIn reactions are needed for solving a wide spectrum of scientific and technical tasks. The excitation function of "2"8Si(n,p)"2"8Al reaction refers to the nuclear data involved in fusion reactor design calculations. The "2"8Si(n,p)"2"8Al reaction is interesting also as the monitor reaction for measurements at fusion facilities. Activation detectors on the basis of the 31P(n,p)31Si reaction are commonly used in the reactor dosimetry. The "1"1"3In(n,γ)"1"1"4"mIn reaction is promising regarding reactor dosimetry application for two reasons. First, due to the "1"1"4"mIn decay parameters which are rather suitable for activation measurements. Half-life of "1"1"4"mIn is equal to T_1/_2 = (49.51 ± 0.01) days and gamma spectrum accompanying decay has only one line with energy 190.27 keV and intensity (15.56 ± 0.15)%. Second, the "1"1"3In(n,γ)"1"1"4"mIn reaction rate may be measured by using one activation detector simultaneously with the "1"1"5In(n,γ)"1"1"6"mIn reaction. Preliminary analysis of existing evaluated excitation functions for "2"8Si(n,p)"2"8Al, "3"1P(n,p)"3"1Si and "1"1"3In(n,γ)"1"1"4"mIn reactions show that new evaluations are needed for all above mentioned reactions. This report is devoted to the preparation of the new evaluations of cross sections data and related covariance matrixes of uncertainties for the "2"8Si(n,p)"2"8Al, "3"1P(n,p)"3"1Si and "1"1"3In(n,γ)"1"1"4"mIn reactions.

Nicotine can skew the characterization of the macrophage type-1 (M{Phi}1) phenotype differentiated with granulocyte-macrophage colony-stimulating factor to the M{Phi}2 phenotype

Energy Technology Data Exchange (ETDEWEB)

Yanagita, Manabu; Kobayashi, Ryohei [Department of Periodontology, Division of Oral Biology and Disease Control, Osaka University Graduate School of Dentistry, Osaka 565-0871 (Japan); Murakami, Shinya, E-mail: ipshinya@dent.osaka-u.ac.jp [Department of Periodontology, Division of Oral Biology and Disease Control, Osaka University Graduate School of Dentistry, Osaka 565-0871 (Japan)

2009-10-09

Macrophages (M{Phi}s) exhibit functional heterogeneity and plasticity in the local microenvironment. Recently, it was reported that M{Phi}s can be divided into proinflammatory M{Phi}s (M{Phi}1) and anti-inflammatory M{Phi}s (M{Phi}2) based on their polarized functional properties. Here, we report that nicotine, the major ingredient of cigarette smoke, can modulate the characteristics of M{Phi}1. Granulocyte-macrophage colony-stimulating factor-driven M{Phi}1 with nicotine (Ni-M{Phi}1) showed the phenotypic characteristics of M{Phi}2. Like M{Phi}2, Ni-M{Phi}1 exhibited antigen-uptake activities. Ni-M{Phi}1 suppressed IL-12, but maintained IL-10 and produced high amounts of MCP-1 upon lipopolysaccharide stimulation compared with M{Phi}1. Moreover, we observed strong proliferative responses of T cells to lipopolysaccharide-stimulated M{Phi}1, whereas Ni-M{Phi}1 reduced T cell proliferation and inhibited IFN-{gamma} production by T cells. These results suggest that nicotine can change the functional characteristics of M{Phi} and skew the M{Phi}1 phenotype to M{Phi}2. We propose that nicotine is a potent regulator that modulates immune responses in microenvironments.

Dual role of YM1+ M2 macrophages in allergic lung inflammation

NARCIS (Netherlands)

Draijer, Christina; Robbe, Patricia; Boorsma, Carian E; Hylkema, Machteld N; Melgert, Barbro N

2018-01-01

Alternatively activated (M2 or YM1+) macrophages have been associated with the development of asthma but their contribution to disease initiation and progression remains unclear. To assess the therapeutic potential of modulating these M2 macrophages, we have studied inhibition of M2 polarisation

The computer code EURDYN-1M (release 2). User's manual

International Nuclear Information System (INIS)

1982-01-01

EURDYN-1M is a finite element computer code developed at J.R.C. Ispra to compute the response of two-dimensional coupled fluid-structure configurations to transient dynamic loading for reactor safety studies. This report gives instructions for preparing input data to EURDYN-1M, release 2, and describes a test problem in order to illustrate both the input and the output of the code

Thermoelectric properties of p-type Ag{sub 1−x}(Pb{sub 1−y}Sn{sub y}){sub m}Sb{sub 1−z}Te{sub m+2}

Energy Technology Data Exchange (ETDEWEB)

Ahn, Kyunghan [Department of Chemistry, Northwestern University, Evanston, IL 60208 (United States); Center for Nanoparticle Research, Institute for Basic Science, (IBS), Seoul 151-742 (Korea, Republic of); Kong, Huijun; Uher, Ctirad [Department of Physics, University of Michigan, Ann Arbor, MI 48109 (United States); Kanatzidis, Mercouri G., E-mail: m-kanatzidis@northwestern.edu [Department of Chemistry, Northwestern University, Evanston, IL 60208 (United States)

2016-10-15

The thermoelectric properties of Ag{sub 1−x}(Pb{sub 1−y}Sn{sub y}){sub m}Sb{sub 1−z}Te{sub m+2} (4≤m≤16, −0.1≤x≤0.3, 1/3≤y≤2/3, 0.2≤z≤0.4; Lead Antimony Silver Tellurium Tin, LASTT-m) compositions were investigated in the temperature range of 300 to ~670 K. All samples crystallize in the average NaCl-type structure without any noticeable second phase and exhibit very narrow bandgaps of <0.1 eV. We studied a range of m values, silver concentrations (x), Pb/Sn ratios (y), and antimony concentrations (z) to determine their effects on the thermoelectric properties. The samples were investigated as melt grown polycrystalline ingots. Varying the Ag contents, the Pb/Sn ratios, and the Sb contents off-stoichiometry allowed us to control the electrical conductivity, the Seebeck coefficient, and the thermal conductivity. The electrical conductivity tends to decrease with decreasing m values. The highest ZT of ~1.1 was achieved at ~660 K for Ag{sub 0.9}Pb{sub 5}Sn{sub 5}Sb{sub 0.8}Te{sub 12} mainly due to the very low lattice thermal conductivity of ~0.4 W/(m K) around 660 K. Also, samples with charge-balanced stoichiometries, Ag(Pb{sub 1−y}Sn{sub y}){sub m}SbTe{sub m+2}, were studied and found to exhibit a lower power factor and higher lattice thermal conductivity than the Ag{sub 1−x}(Pb{sub 1−y}Sn{sub y}){sub m}Sb{sub 1−z}Te{sub m+2} compositions. - Graphical abstract: The Ag{sub 1−x}(Pb{sub 1−y}Sn{sub y}){sub m}Sb{sub 1−z}Te{sub m+2} system defines a complex and flexible class of tunable thermoelectric class of materials with high performance.

A new series of oxycarbonate superconductors (Cu{sub 0.5}C{sub 0.5}){sub m}Ba{sub m+1}Ca{sub n-1}Cu{sub n}O{sub 2}({sub m+n})+1

Energy Technology Data Exchange (ETDEWEB)

Takayama-Muromachi, E.; Kawashima, T.; Matsui, Y. [National Institute for Research in Inorganic Materials, Ibaraki (Japan)

1994-12-31

We found a new series of oxycarbonate superconductors in the Ba-Ca-Cu-C-O system under high pressure of 5 GPa. Their ideal formula is (Cu{sub 0.5}C{sub 0.5}){sub m}Ba{sub m+1}Ca{sub n-1}Cu{sub n}O{sub 2}({sub m+n})+1 ((Cu,C)-m(m+1)(n-1)n). Thus far, n=3, 4 members of the m=1 series, (Cu,C)-1223 and (Cu,C)-1234, have been prepared in bulk while n=4, 5 members, (Cu,C)-2334 and (Cu,C)-2345, have been prepared for the m=2 series. (Cu,C)-1223 shows superconductivity below 67 K while T{sub c}`s of other compounds are above 110 K. In particular, (Cu,C)=1234 has the highest T{sub c} of 117 K.

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

Science.gov (United States)

2011-01-06

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

USPIO-labeling in M1 and M2-polarized macrophages: An in vitro study using a clinical magnetic resonance scanner.

Science.gov (United States)

Zini, Chiara; Venneri, Mary A; Miglietta, Selenia; Caruso, Damiano; Porta, Natale; Isidori, Andrea M; Fiore, Daniela; Gianfrilli, Daniele; Petrozza, Vincenzo; Laghi, Andrea

2018-08-01

Aim of the study was to evaluate USPIO labeling in different macrophage populations using a clinical 3.0T MR unit with optical and electron microscopy as the gold standard. Human monocytic cell line THP-1 cells were differentiated into macrophages. Afterwards, M0 macrophages were incubated with IL-4 and IL-13 in order to obtain M2 polarized macrophages or with IFN-gamma and LPS for classical macrophage activation (M1). These groups were incubated with USPIO-MR contrast agent (P904) for 36 hr; M0, M0 + P904, M1 +  P904, and M2 + P904 were analyzed in gel phantoms with a 3.0T MR scanner. m-RNA of M1 and M2 markers confirmed the polarization of THP-1-derived macrophages. M2 + P904 showed a much higher T1 signal (p <  0.0001), a significantly lower (p < 0.0001) T2* signal, and significantly higher R* (p < 0.0001) compared to the other populations. Hystological analysis confirmed higher iron content in the M2-polarized population compared to both M1-polarized (p = 0.04) and M0-P904 (p = 0.003). Ultrastructure analysis demonstrated ubiquitous localization of P904 within the cellular compartments. Our results demonstrate that a selective USPIO-labeling of different macrophage populations can be detected in vitro using the 3.0T clinical scanner. © 2017 Wiley Periodicals, Inc.

Absorption by water vapour in the 1 to 2 μm region

International Nuclear Information System (INIS)

Smith, K.M.; Ptashnik, I.; Newnham, D.A.; Shine, K.P.

2004-01-01

The near-IR (in the range 5000-10 000 cm -1 , 1-2 μm) bands of water vapour have been measured in absorption in the laboratory at sub-Doppler spectral resolution (up to 0.0054 cm -1 after numerical apodisation) by Fourier transform spectroscopy. Measurements have been made at 296 K on pure water vapour (at pressures between 2 and 20 hPa) and mixtures of water and air (at total pressures of 100 and 1000 hPa), at optical path lengths in the range 0.26-9.75 m. Measured absorption intensities have been compared with values calculated using the HITRAN 2000 molecular database. These comparisons indicate that the intensities of the 2ν(1.4 μm) and 2ν+δ(1.14 μm) bands are underestimated in HITRAN 2000 by approximately 15% and 20%, respectively, for pure water vapour measurements, and 12% for both bands in the case of water-air mixtures. The ν+δ (1.86 μm) band is in good agreement (0.4% for pure water vapour and less than 6% for mixtures with air) with HITRAN 2000. For typical atmospheric conditions, these absorption bands are sufficiently strong that radiation is fully absorbed at wavelengths in the region of the band centres. Hence the extra absorption that has been identified has only a modest impact (0.16 W m -2 or about 0.2%) on the global-mean clear-sky absorption of solar radiation. The impact in the upper troposphere is several times larger

A Survey on M2M Service Networks

Directory of Open Access Journals (Sweden)

Juhani Latvakoski

2014-11-01

Full Text Available The number of industrial applications relying on the Machine to Machine (M2M services exposed from physical world has been increasing in recent years. Such M2M services enable communication of devices with the core processes of companies. However, there is a big challenge related to complexity and to application-specific M2M systems called “vertical silos”. This paper focuses on reviewing the technologies of M2M service networks and discussing approaches from the perspectives of M2M information and services, M2M communication and M2M security. Finally, a discussion on technologies and approaches potentially enabling future autonomic M2M service networks are provided. According to our conclusions, it is seen that clear definition of the architectural principles is needed to solve the “vertical silo” problem and then, proceeding towards enabling autonomic capabilities for solving complexity problem appears feasible. Several areas of future research have been identified, e.g., autonomic information based services, optimization of communications with limited capability devices, real-time messaging, creation of trust and end to end security, adaptability, reliability, performance, interoperability, and maintenance.

III. The effect of various doses of gamma 6OCo radiation upon pollen vitality of China aster (Callistephus chinensis Nees in M1 and M2 generation

Directory of Open Access Journals (Sweden)

Alicja Wosińska

2013-12-01

Full Text Available The effect of gamma radiation upon pollen was studied in populations of 4 China aster varieties in M1 (plants from irradiated seeds and M2 generation. Effect of radiation Was assessed·in partiicular years. Comparison was rnalde between pollen vitality in irradiated plants and in the control. Effect of radiation was visibly harmful only in case of plants from M1 generation. The effects of radiation were different for particular varieties.

Effects of muscarinic receptor antagonists on cocaine discrimination in wild-type mice and in muscarinic receptor M1, M2, and M4 receptor knockout mice.

Science.gov (United States)

Joseph, Lauren; Thomsen, Morgane

2017-06-30

Muscarinic M 1 /M 4 receptor stimulation can reduce abuse-related effects of cocaine and may represent avenues for treating cocaine addiction. Muscarinic antagonists can mimic and enhance effects of cocaine, including discriminative stimulus (S D ) effects, but the receptor subtypes mediating those effects are not known. A better understanding of the complex cocaine/muscarinic interactions is needed to evaluate and develop potential muscarinic-based medications. Here, knockout mice lacking M 1 , M 2 , or M 4 receptors (M 1 -/- , M 2 -/- , M 4 -/- ), as well as control wild-type mice and outbred Swiss-Webster mice, were trained to discriminate 10mg/kg cocaine from saline. Muscarinic receptor antagonists with no subtype selectivity (scopolamine), or preferential affinity at the M 1 , M 2 , or M 4 subtype (telenzepine, trihexyphenidyl; methoctramine, AQ-RA 741; tropicamide) were tested alone and in combination with cocaine. In intact animals, antagonists with high affinity at M 1 /M 4 receptors partially substituted for cocaine and increased the S D effect of cocaine, while M 2 -preferring antagonists did not substitute, and reduced the S D effect of cocaine. The cocaine-like effects of scopolamine were absent in M 1 -/- mice. The cocaine S D attenuating effects of methoctramine were absent in M 2 -/- mice and almost absent in M 1 -/- mice. The findings indicate that the cocaine-like S D effects of muscarinic antagonists are primarily mediated through M 1 receptors, with a minor contribution of M 4 receptors. The data also support our previous findings that stimulation of M 1 receptors and M 4 receptors can each attenuate the S D effect of cocaine, and show that this can also be achieved by blocking M 2 autoreceptors, likely via increased acetylcholine release. Copyright © 2017 Elsevier B.V. All rights reserved.

M2-F1 lifting body and Paresev 1B on ramp

Science.gov (United States)

1963-01-01

In this photo of the M2-F1 lifting body and the Paresev 1B on the ramp, the viewer sees two vehicles representing different approaches to building a research craft to simulate a spacecraft able to land on the ground instead of splashing down in the ocean as the Mercury capsules did. The M2-F1 was a lifting body, a shape able to re-enter from orbit and land. The Paresev (Paraglider Research Vehicle) used a Rogallo wing that could be (but never was) used to replace a conventional parachute for landing a capsule-type spacecraft, allowing it to make a controlled landing on the ground. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop

Generation of 2.1 m wavelength from degenerate high gray track ...

Indian Academy of Sciences (India)

2014-02-12

Feb 12, 2014 ... Home; Journals; Pramana – Journal of Physics; Volume 82; Issue 2. Generation of 2.1 m wavelength from degenerate high gray track resistant potassium titanyl phosphate optical parametric oscillator. S Verma C Mishra V Kumar M Yadav K C Bahuguna N S Vasan S P Gaba. Contributed Papers Volume ...

Comparison between repaglinide and glipizide in Type 2 diabetes mellitus: a 1-year multicentre study

DEFF Research Database (Denmark)

Madsbad, Sten; Kilhovd, B; Lager, I

2001-01-01

AIMS: To evaluate the long-term effectiveness and safety of repaglinide, a novel prandial glucose regulator, in comparison with glipizide in the treatment of patients with Type 2 diabetes. METHODS: Diet or tablet-treated patients with Type 2 diabetes (n = 256; age 40-75 years, body mass index (BMI...... with Type 2 diabetes, and is better than glipizide in controlling HbA1c and FBG levels, overall, and in OHA-naive patients.......) 20-35 kg/m2, HbA1c 4.2-12.8%), without signs of severe microvascular or macrovascular complications, were included in this double-blind, multicentre, parallel-group comparative trial. Patients were randomized at a 2:1 ratio to repaglinide, 1-4 mg at mealtimes, or glipizide, 5-15 mg daily. RESULTS...

Electronographic calibration of UK 1.2-m Schmidt plates

International Nuclear Information System (INIS)

Hawkins, M.R.S.

1979-01-01

Two electronographic sequences are given in the South Galactic Pole region down to msub(B) = approximately 23 +- 0.3 mag. These sequences are used to obtain a calibration for COSMOS measures of UK 1.2-m Schmidt plates and evaluate their photometric transfer properties. (author)

Trichoderma asperelloides Spores Downregulate dectin1/2 and TLR2 Receptors of Mice Macrophages and Decrease Candida parapsilosis Phagocytosis Independent of the M1/M2 Polarization

Directory of Open Access Journals (Sweden)

Andréa G. dos Santos

2017-09-01

Full Text Available The intensive use of pesticides to control pests in agriculture has promoted several issues relating to environment. As chemical pesticides remain controversial, biocontrol agents originating from fungi could be an alternative. Among them, we highlight biocontrol agents derived from the fungi genus Trichoderma, which have been documented in limiting the growth of other phytopathogenic fungus in the roots and leaves of several plant species. An important member of this genus is Trichoderma asperelloides, whose biocontrol agents have been used to promote plant growth while also treating soil diseases caused by microorganisms in both greenhouses and outdoor crops. To evaluate the safety of fungal biological agents for human health, tests to detect potentially adverse effects, such as allergenicity, toxicity, infectivity and pathogenicity, are crucial. In addition, identifying possible immunomodulating properties of fungal biocontrol agents merits further investigation. Thus, the aim of this study was to evaluate the effects of T. asperelloides spores in the internalization of Candida parapsilosis yeast by mice phagocytes, in order to elucidate the cellular and molecular mechanism of this interaction, as a model to understand possible in vivo effects of this fungus. For this, mice were exposed to a fungal spore suspension through-intraperitoneal injection, euthanized and cells from the peripheral blood and peritoneal cavity were collected for functional, quantitative and phenotypic analysis, throughout analysis of membrane receptors gene expression, phagocytosis ability and cells immunophenotyping M1 (CCR7 and CD86 and M2 (CCR2 and CD206. Our analyses showed that phagocytes exposed to fungal spores had reduced phagocytic capacity, as well as a decrease in the quantity of neutrophils and monocytes in the peripheral blood and peritoneal cavity. Moreover, macrophages exposed to T. asperelloides spores did not display the phenotypic profile M1/M2, and

mPGES-1-derived prostaglandin E2 stimulates Stat3 to promote podocyte apoptosis.

Science.gov (United States)

Yu, Jing; Wu, Yimei; Wang, Lu; Zhang, Wen; Xu, Man; Song, Jiayu; Fu, Yu; Cui, Yiyun; Gong, Wei; Li, Shuzhen; Xia, Weiwei; Huang, Songming; Zhang, Aihua; Jia, Zhanjun

2017-11-01

We previously reported that microsomal prostaglandin E synthase-1 (mPGES-1) contributed to adriamycin (Adr)-induced podocyte apoptosis. However, the molecular mechanism remains unclear. Here we studied the role of mPGES-1/PGE2 cascade in activating Stat3 signaling and the contribution of Stat3 in PGE2- and Adr-induced podocyte apoptosis. In murine podocytes, PGE2 dose- and time-dependently increased the phosphorylation of Stat3 in line with the enhanced cell apoptosis and reduced podocyte protein podocin. In agreement with the increased Stat3 phosphorylation, Stat3-derived cytokines including IL-6, IL-17, MCP-1, and ICAM-1 were significantly upregulated following PGE2 treatment. By application of a specific Stat3 inhibitor S3I-201, PGE2-induced podocyte apoptosis was largely abolished in parallel with a blockade of podocin reduction. Next, we observed that Adr treatment also enhanced p-Stat3 and activated mPGES-1/PGE2 cascade. Blockade of Stat3 by S3I-201 significantly ameliorated Adr-induced cell apoptosis and podocin reduction. More interestingly, silencing mPGES-1 in podocytes by mPGES-1 siRNA blocked Adr-induced increments of Stat-3 phosphorylation, PGE2 production, and Stat3-derived inflammatory cytokines. Taken together, this study suggested that mPGES-1-derived PGE2 could activate Stat3 signaling to promote podocyte apoptosis. Targeting mPGES-1/PGE2/Stat3 signaling might be a potential strategy for the treatment of podocytopathy.

Combined adenovirus-mediated artificial microRNAs targeting mfgl2, mFas, and mTNFR1 protect against fulminant hepatic failure in mice.

Directory of Open Access Journals (Sweden)

Dong Xi

Full Text Available Hepatitis B virus (HBV-related acute-on-chronic liver failure (ACLF has a poor prognosis with high in-hospital mortality. Hepatic and circulating inflammatory cytokines, such as fibrinogen like protein 2 (fgl2, FasL/Fas, and TNFα/TNFR1, play a significant role in the pathophysiology of ACLF. This study aimed to investigate the therapeutic effect of recombinant adenoviral vectors carrying constructed DNA code for non-native microRNA (miRNA targeting mouse fgl2 (mfgl2 or both mFas and mTNFR1 on murine hepatitis virus (MHV-3-induced fulminant hepatitis in BALB/cJ mice. Artificial miRNA eukaryotic expression plasmids against mfgl2, mFas, and mTNFR1 were constructed, and their inhibitory effects on the target genes were confirmed in vitro. pcDNA6.2-mFas-mTNFR1- miRNA，which expresses miRNA against both mFas and mTNFR1 simultaneously，was constructed. To construct a miRNA adenovirus expression vector against mfgl2, pcDNA6.2-mfgl2-miRNA was cloned using Gateway technology. Ad-mFas-mTNFR1- miRNA was also constructed by the same procedure. Adenovirus vectors were delivered by tail-vein injection into MHV-3-infected BALB/cJ mice to evaluate the therapeutic effect. 8 of 18 (44.4% mice recovered from fulminant viral hepatitis in the combined interference group treated with Ad-mfgl2-miRNA and Ad-mFas-mTNFR1-miRNA. But only 4 of 18 (22.2% mice receiving Ad-mfgl2-miRNA and 3 of 18 (16.7% mice receiving Ad-mFas-mTNFR1- miRNA survived. These adenovirus vectors significantly ameliorated inflammatory infiltration, fibrin deposition, hepatocyte necrosis and apoptosis, and prolonged survival time. Our data illustrated that combined interference using adenovirus-mediated artificial miRNAs targeting mfgl2, mFas, and mTNFR1 might have significant therapeutic potential for the treatment of fulminant hepatitis.

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

International Nuclear Information System (INIS)

Goodrich, R.W.

1991-01-01

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

Efficacy of laparoscopic greater curvature plication for weight loss and type 2 diabetes: 1-year follow-up.

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Taha, Osama

2012-10-01

Laparoscopic greater curvature plication (LGCP) has gained popularity within the last 2 years because it is a restrictive procedure that reduces gastric volume without the need for stomach resection. A prospective study was performed in which 55 morbidly obese patients with type 2 diabetes (44 female, 11 male) underwent LGCP. The patients had a mean age of 38.5 years (22-55 years), mean BMI of 43.5 kg/m(2) (35-52 kg/m(2)), and mean glycosylated hemoglobin (HbA1c) of 7.9 % (6-10 %). All procedures were completed laparoscopically. The mean operative time was 55 min (40-80 min), and the mean hospital stay was 1.8 days (1.5-5 days). No intraoperative or postoperative complications were reported apart from three cases of resistant nausea and vomiting and one case of intraluminal bleeding. The mean excess weight loss (EWL%) was 35 % (30-65 %) after 12 months with a mean BMI of 38 kg/m(2) after 12 months. A total of 23 % of patients stopped losing weight 6 months after the procedure, and 11 % began regaining about 14 % (12-20 %) of their EWL 9 months after the procedure. The mean HbA1c was 7.5 % (5.5-8 %) after 12 months. LGCP is feasible and safe in the short term when applied to morbidly obese patients, but may be unsustainable. It is inferior as a restrictive procedure for resolution of type 2 diabetes. Longer follow-up and prospective comparative trials are needed to clarify whether it can be considered an effective single-stage procedure for treating morbidly obese diabetic patients and their comorbidities.

Regulation of Human Macrophage M1–M2 Polarization Balance by Hypoxia and the Triggering Receptor Expressed on Myeloid Cells-1

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Federica Raggi

2017-09-01

Full Text Available Macrophages (Mf are a heterogeneous population of tissue-resident professional phagocytes and a major component of the leukocyte infiltrate at sites of inflammation, infection, and tumor growth. They can undergo diverse forms of activation in response to environmental factors, polarizing into specialized functional subsets. A common hallmark of the pathologic environment is represented by hypoxia. The impact of hypoxia on human Mf polarization has not been fully established. The objective of this study was to elucidate the effects of a hypoxic environment reflecting that occurring in vivo in diseased tissues on the ability of human Mf to polarize into classically activated (proinflammatory M1 and alternatively activated (anti-inflammatory M2 subsets. We present data showing that hypoxia hinders Mf polarization toward the M1 phenotype by decreasing the expression of T cell costimulatory molecules and chemokine homing receptors and the production of proinflammatory, Th1-priming cytokines typical of classical activation, while promoting their acquisition of phenotypic and secretory features of alternative activation. Furthermore, we identify the triggering receptor expressed on myeloid cells (TREM-1, a member of the Ig-like immunoregulatory receptor family, as a hypoxia-inducible gene in Mf and demonstrate that its engagement by an agonist Ab reverses the M2-polarizing effect of hypoxia imparting a M1-skewed phenotype to Mf. Finally, we provide evidence that Mf infiltrating the inflamed hypoxic joints of children affected by oligoarticular juvenile idiopatic arthritis express high surface levels of TREM-1 associated with predominant M1 polarization and suggest the potential of this molecule in driving M1 proinflammatory reprogramming in the hypoxic synovial environment.

Regulation of Human Macrophage M1–M2 Polarization Balance by Hypoxia and the Triggering Receptor Expressed on Myeloid Cells-1

Science.gov (United States)

Raggi, Federica; Pelassa, Simone; Pierobon, Daniele; Penco, Federica; Gattorno, Marco; Novelli, Francesco; Eva, Alessandra; Varesio, Luigi; Giovarelli, Mirella; Bosco, Maria Carla

2017-01-01

Macrophages (Mf) are a heterogeneous population of tissue-resident professional phagocytes and a major component of the leukocyte infiltrate at sites of inflammation, infection, and tumor growth. They can undergo diverse forms of activation in response to environmental factors, polarizing into specialized functional subsets. A common hallmark of the pathologic environment is represented by hypoxia. The impact of hypoxia on human Mf polarization has not been fully established. The objective of this study was to elucidate the effects of a hypoxic environment reflecting that occurring in vivo in diseased tissues on the ability of human Mf to polarize into classically activated (proinflammatory M1) and alternatively activated (anti-inflammatory M2) subsets. We present data showing that hypoxia hinders Mf polarization toward the M1 phenotype by decreasing the expression of T cell costimulatory molecules and chemokine homing receptors and the production of proinflammatory, Th1-priming cytokines typical of classical activation, while promoting their acquisition of phenotypic and secretory features of alternative activation. Furthermore, we identify the triggering receptor expressed on myeloid cells (TREM)-1, a member of the Ig-like immunoregulatory receptor family, as a hypoxia-inducible gene in Mf and demonstrate that its engagement by an agonist Ab reverses the M2-polarizing effect of hypoxia imparting a M1-skewed phenotype to Mf. Finally, we provide evidence that Mf infiltrating the inflamed hypoxic joints of children affected by oligoarticular juvenile idiopatic arthritis express high surface levels of TREM-1 associated with predominant M1 polarization and suggest the potential of this molecule in driving M1 proinflammatory reprogramming in the hypoxic synovial environment. PMID:28936211

Thermodynamic properties of CuCr2S4 solid solutions in Cusub(1/2)Msub(1/2)Crsub(2)Ssub(4) (M - Ga, In)

International Nuclear Information System (INIS)

Titov, V.V.; Kesler, Ya.A.; Shelkotunov, V.A.; Gordeev, I.V.; Tret'yakov, Yu.D.

1985-01-01

By means of an adiabatic calorimeter and quartz dilatometer for CuCr 2 S 4 in Cusub(1/2)Msub(1/2)Crsub(2)Ssub(4) (M-Ga, In) temperature dependences of heat capacity are determined. The contribution of various components into heat capacity is estimated, thermodynamic parameters of magnetic transformation are calculated

Comparative study of A-site order in the lead-free bismuth titanates M1/2Bi1/2TiO3 (M=Li, Na, K, Rb, Cs, Ag, Tl) from first-principles

International Nuclear Information System (INIS)

Gröting, Melanie; Albe, Karsten

2014-01-01

We investigate the possibility of enhancing chemical order in the relaxor ferroelectric Na 1/2 Bi 1/2 TiO 3 upon substitution of Na + by other monovalent cations M + using total energy calculations based on density functional theory. All chemically available monovalent cations M + , which are Li, Na, Ag, K, Tl, Rb and Cs, are considered and an analysis of the structurally relaxed structures in terms of symmetry-adapted distortion modes is given in order to quantify the chemically induced structural distortions. We demonstrate that the replacement of Na + by other monovalent cations can hardly alter the tendency of chemical order with respect to Na 1/2 Bi 1/2 TiO 3 . Only Tl 1/2 Bi 1/2 TiO 3 and Ag 1/2 Bi 1/2 TiO 3 show enhanced tendency for chemical ordering. Both heavy metals behave similar to the light alkali metals in terms of structural relaxations and relative stabilities of the ordered configurations. Although a comparison of the Goldschmidt factors of components (M TiO 3 ) − reveals for Tl a value above the upper stability limit for perovskites, the additional lone-pair effect of Tl + stabilizes the ordered structure. - Graphical abstract: Amplitudes of chemically induced distortion modes in different ordered perovskites M 1/2 Bi 1/2 TiO 3 and visualisation of atomic displacements associated with distortion mode X + 1 in the 001-ordered compounds Li 1/2 Bi 1/2 TiO 3 and Cs 1/2 Bi 1/2 TiO 3 . Due to a substantial size mismatch between bismuth (green) and caesium (dark blue), incorporation of the latter leads to enhanced displacements of oxygen atoms (red) and suppresses displacements of titanium (silver) as compared to lithium (light blue) or other smaller monovalent cations. - Highlights: • Lead-free A-site mixed bismuth titanates M 1/2 Bi 1/2 TiO 3 are studied by first-principles calculations. • Investigation of chemical ordering tendency for M=Li, Na, K, Rb, Cs, Ag, and Tl. • Group theoretical analysis of different ordered structures. • Ag and Tl

Quaternary Pt{sub 2}Ru{sub 1}Fe{sub 1}M{sub 1}/C (M=Ni, Mo, or W) catalysts for methanol electro-oxidation reaction

Energy Technology Data Exchange (ETDEWEB)

Jeon, Min Ku; Lee, Ki Rak; Kang, Kweon Ho; Park, Geun Il [Korea Atomic Energy Research Institute, Daejeon (Korea, Republic of); Jeon, Hyung Joon [Kyoto University, Kyoto (Japan); McGinn, Paul J. [University of Notre Dame, Indiana (United States)

2015-02-15

Quaternary Pt{sub 2}Ru{sub 1}Fe{sub 1}M{sub 1}/C (M=Ni, Mo, or W) catalysts were investigated for the methanol electro-oxidation reaction (MOR). Electrocatalytic activities of the quaternary catalysts for CO electro-oxidation were studied via CO stripping experiments, and the Pt{sub 2}Ru{sub 1}Fe{sub 1}Ni{sub 1}/C and Pt{sub 2}Ru{sub 1}Fe{sub 1}W{sub 1}/C catalysts exhibited lowered on-set potential compared to that of a commercial PtRu/C catalyst. MOR activities of the quaternary catalysts were determined by linear sweep voltammetry (LSV) experiments, and the Pt{sub 2}Ru{sub 1}Fe{sub 1}W{sub 1}/C catalyst outperformed the commercial PtRu/C catalyst by 170 and 150% for the mass and specific activities, respectively. X-ray photoelectron spectroscopy (XPS) was employed to analyze surface oxidation states of constituent atoms, and it was identified that the structure of the synthesized catalysts are close to a nano-composite of Pt and constituent metal hydroxides and oxides. In addition, the XPS results suggested that the bi-functional mechanism accounts for the improved performance of the Pt{sub 2}Ru{sub 1}Fe{sub 1}Ni{sub 1}/C and Pt{sub 2}Ru{sub 1} Fe{sub 1}W{sub 1}/C catalysts.

Spatial patterns and temporal changes in atmospheric-mercury deposition for the midwestern USA, 2001–2016

Science.gov (United States)

Risch, Martin R.; Kenski, Donna M.

2018-01-01

Spatial patterns and temporal changes in atmospheric-mercury (Hg) deposition were examined in a five-state study area in the Midwestern USA where 32% of the stationary sources of anthropogenic Hg emissions in the continental USA were located. An extensive monitoring record for wet and dry Hg deposition was compiled for 2001–2016, including 4666 weekly precipitation samples at 13 sites and 27 annual litterfall-Hg samples at 7 sites. This study is the first to examine these Hg data for the Midwestern USA. The median annual precipitation-Hg deposition at the study sites was 10.4 micrograms per square meter per year (ug/m2/year) and ranged from 5.8 ug/m2/year to 15.0 ug/m2/year. The median annual Hg concentration was 9.4 ng/L. Annual litterfall-Hg deposition had a median of 16.1 ug/m2/year and ranged from 9.7 to 23.4 ug/m2/year. Isopleth maps of annual precipitation-Hg deposition indicated a recurring spatial pattern similar to one revealed by statistical analysis of weekly precipitation-Hg deposition. In that pattern, high Hg deposition in southeastern Indiana was present each year, frequently extending to southern Illinois. Most of central Indiana and central Illinois had similar Hg deposition. Areas with comparatively lower annual Hg deposition were observed in Michigan and Ohio for many years and frequently included part of northern Indiana. The area in southern Indiana where high Hg deposition predominated had the highest number of extreme episodes of weekly Hg deposition delivering up to 15% of the annual Hg load from precipitation in a single week. Modeled 48-h back trajectories indicated air masses for these episodes often arrived from the south and southwest, crossing numerous stationary sources of Hg emissions releasing from 23 to more than 300 kg Hg per year. This analysis suggests that local and regional, rather than exclusively continental or global Hg emissions were likely contributing to the extreme episodes and at least in part, to the spatial

ABCG2-overexpressing S1-M1-80 cell xenografts in nude mice keep original biochemistry and cell biological properties.

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Wang, Fang; Liang, Yong-Ju; Wu, Xing-Ping; Su, Xiao-Dong; Fu, Li-Wu

2012-03-01

S1-M1-80 cells, derived from human colon carcinoma S1 cells, are mitoxantrone-selected ABCG2-overexpressing cells and are widely used in in vitro studies of multidrug resistance(MDR). In this study, S1-M1-80 cell xenografts were established to investigate whether the MDR phenotype and cell biological properties were maintained in vivo. Our results showed that the proliferation, cell cycle, and ABCG2 expression level in S1-M1-80 cells were similar to those in cells isolated from S1-M1-80 cell xenografts (named xS1-M1-80 cells). Consistently, xS1-M1-80 cells exhibited high levels of resistance to ABCG2 substrates such as mitoxantrone and topotecan, but remained sensitive to the non-ABCG2 substrate cisplatin. Furthermore, the specific ABCG2 inhibitor Ko143 potently sensitized xS1-M1-80 cells to mitoxantrone and topotecan. These results suggest that S1-M1-80 cell xenografts in nude mice retain their original cytological characteristics at 9 weeks. Thus, this model could serve as a good system for further investigation of ABCG2-mediated MDR.

Respiratory syncytial virus M2-1 protein induces the activation of nuclear factor kappa B

Energy Technology Data Exchange (ETDEWEB)

Reimers, Kerstin [Klinik fuer Plastische, Hand-und Wiederherstellungschirurgie, Podbielskistrasse 380, D-30659 Hannover (Germany); Buchholz, Katja [Institut fuer Medizinische Mikrobiologie, Otto-von-Guericke-Universitaet Magdeburg, Leipzigerstrasse 44, D-39120 Magdeburg (Germany); Werchau, Hermann [Institut fuer Medizinische Mikrobiologie, Otto-von-Guericke-Universitaet Magdeburg, Leipzigerstrasse 44, D-39120 Magdeburg (Germany)

2005-01-20

Respiratory syncytial virus (RSV) induces the production of a number of cytokines and chemokines by activation of nuclear factor kappa B (NF-{kappa}B). The activation of NF-{kappa}B has been shown to depend on viral replication in the infected cells. In this study, we demonstrate that expression of RSV M2-1 protein, a transcriptional processivity and anti-termination factor, is sufficient to activate NF-{kappa}B in A549 cells. Electromobility shift assays show increased NF-{kappa}B complexes in the nuclei of M2-1-expressing cells. M2-1 protein is found in nuclei of M2-1-expressing cells and in RSV-infected cells. Co-immunoprecipitations of nuclear extracts of M2-1-expressing cells and of RSV-infected cells revealed an association of M2-1 with Rel A protein. Furthermore, the activation of NF-{kappa}B depends on the C-terminus of the RSV M2-1 protein, as shown by NF-{kappa}B-induced gene expression of a reporter gene construct.

N,N'-di-(m-methylphenyi)-3,6-dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamide (ZGDHu-1) suppresses the proliferation of PANC-1 pancreatic cancer cells via apoptosis and G2/M cell cycle arrest.

Science.gov (United States)

Chen, Su-Feng; Xia, Jun; Lv, Ya-Ping; Liu, Jin-Lin; Li, Wan-Xiang; Yu, Xi-Ping; Hu, Wei-Xiao; Zhou, Yong-Lie

2015-04-01

Pancreatic cancer is one of the human gastrointestinal malignancies with a high mortality and poor prognosis. Approximately eighty percent of patients are diagnosed with unresectable or metastatic disease. Thus, development of novel chemicals in the treatment of pancreatic cancer is imperative. This study aimed to investigate the anticancer effects of N,N'-di-(m-methylphenyi)-3,6-dimethyl-1,4-dihydro-1,2,4,5-tetrazine-1,4-dicarboamide (ZGDHu-1), a new tetrazine derivative, on the PANC-1 pancreatic cancer cell line and clarify the underlying molecular mechanism. Using an MTT assay, we found that ZGDHu-1 significantly suppressed the proliferation of PANC-1 cells in a time- and dose-dependent manner. Moreover, according to the morphological and flow cytometric analysis, the results indicated that ZGDHu-1 induced PANC-1 cell apoptosis and G2/M cell cycle arrest in a dose-dependent manner. In the western blot analysis, expression of the pro-apoptotic Bax gene was upregulated while the anti-apoptotic Bcl-2 gene was downregulated following treatment with ZGDHu-1. ZGDHu-1 also activated pro-caspase-3 and PARP and increased the expression of NF-κB inhibitor IκB. Furthermore, the expression levels of G2/M regulatory molecules such as cyclin B1 and cdc2 were decreased while that of Chk1 was increased. These results suggested that ZGDHu-1 suppressed the proliferation of pancreatic cancer cells, rendering it a potential therapeutic drug for the treatment of pancreatic cancer.

Sphingosine kinase-1, S1P transporter spinster homolog 2 and S1P2 mRNA expressions are increased in liver with advanced fibrosis in human.

Science.gov (United States)

Sato, Masaya; Ikeda, Hitoshi; Uranbileg, Baasanjav; Kurano, Makoto; Saigusa, Daisuke; Aoki, Junken; Maki, Harufumi; Kudo, Hiroki; Hasegawa, Kiyoshi; Kokudo, Norihiro; Yatomi, Yutaka

2016-08-26

The role of sphingosine 1-phosphate (S1P) in liver fibrosis or inflammation was not fully examined in human. Controversy exists which S1P receptors, S1P1 and S1P3 vs S1P2, would be importantly involved in its mechanism. To clarify these matters, 80 patients who received liver resection for hepatocellular carcinoma and 9 patients for metastatic liver tumor were enrolled. S1P metabolism was analyzed in background, non-tumorous liver tissue. mRNA levels of sphingosine kinase 1 (SK1) but not SK2 were increased in livers with fibrosis stages 3-4 compared to those with 0-2 and to normal liver. However, S1P was not increased in advanced fibrotic liver, where mRNA levels of S1P transporter spinster homolog 2 (SPNS2) but not S1P-degrading enzymes were enhanced. Furthermore, mRNA levels of S1P2 but not S1P1 or S1P3 were increased in advanced fibrotic liver. These increased mRNA levels of SK1, SPNS2 and S1P2 in fibrotic liver were correlated with α-smooth muscle actin mRNA levels in liver, and with serum ALT levels. In conclusion, S1P may be actively generated, transported to outside the cells, and bind to its specific receptor in human liver to play a role in fibrosis or inflammation. Altered S1P metabolism in fibrotic liver may be their therapeutic target.

Geniposide activates GSH S-transferase by the induction of GST M1 and GST M2 subunits involving the transcription and phosphorylation of MEK-1 signaling in rat hepatocytes

International Nuclear Information System (INIS)

Kuo, W.-H.; Chou, F.-P.; Young, S.-C.; Chang, Y.-C.; Wang, C.-J.

2005-01-01

Geniposide, an iridoid glycoside isolated from the fruit of Gardenia jasminoides Ellis, has biological capabilities of detoxication, antioxidation, and anticarcinogenesis. We have recently found that geniposide possesses a potential for detoxication by inducing GST activity and the expression of GST M1 and GST M2 subunits. In this study, the signaling pathway of geniposide leading to the activation of GSH S-transferase (GST) was investigated. Primary cultured rat hepatocytes were treated with geniposide in the presence or absence of mitogen-activated protein kinase (MAPK) inhibitors and examined for GST activity, expression of GST M1 and M2 subunits, and protein levels of MAPK signaling proteins. Western blotting data demonstrated that geniposide induced increased protein levels of GST M1 and GST M2 (∼1.76- and 1.50-fold of control, respectively). The effect of geniposide on the increased protein levels of GST M1 and GST M2 was inhibited by the MEK-1 inhibitor PD98059, but not by other MAPK inhibitors. The GST M1 and GST M2 transcripts as determined by RT-PCR and GST activity were also inhibited concurrently by the MEK-1 inhibitor PD98059. The protein levels of up- and down-stream effectors of the MEK-1, including Ras, Raf, and Erk1/2, and the phosphorylation state of Erk1/2 were found to be induced by geniposide, indicating a two-phase influence of geniposide. The results suggest that geniposide induced GST activity and the expression of GST M1 and GST M2 acting through MEK-1 pathway by activating and increasing expression of Ras/Raf/MEK-1 signaling mediators

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

Energy Technology Data Exchange (ETDEWEB)

Malmskog, S G; Hoejeberg, M

1967-08-15

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

Detailed profile of m=2 islands with TVTS on JFT-2M

International Nuclear Information System (INIS)

Yamauchi, T.; Grek, B.; Hoshino, K.; Le Blanc, B.; Johnson, D.; Felt, J.; Shiina, T.; Kurita, G.; Ishige, Y.; Kozawa, H.

1996-01-01

The detailed electron temperature profile (spatial resolution: 0.86 cm) of a low density JFT-2M plasma is measured with the TV Thomson scattering system (TVTS). Flat profiles showing the electron temperature shapes of m=2/n=1 islands are presented, which are in contrast to that without islands. On the other hand, the m=2/n=1 islands are effectively suppressed with local ECRH heating. (orig.)

The September 2017 M=8.1 Chiapas and M=7.1 Puebla, Mexico, earthquakes: Chain reaction or coincidence?

Science.gov (United States)

Toda, S.; Stein, R. S.

2017-12-01

The M=8.1 and M=7.1 events struck 12 days and 600 km apart, both with an independent probability of occurrence of 0.5% per year, based on the GEAR model [Bird et al., 2015]. Are they related? First, we calculated the static stress imparted by the M=8.1 shock to the fault that ruptured in the M=7.1, and find a tiny push that would favor rupture. But the stress increase (0.2 kPa) is less than the fault would experience from the tidal stresses, and so it should be inconsequential. We next used the México Servicio Sismológico Nacional (UNAM) online catalog to look at the quakes in the month before the M=8.1 and in the 13 days since. We calculate the completeness to be M≥4.0. There are virtually no remote aftershocks from the Chiapas rupture that extend within 250 km of the M=7.1 shock during the first week after the M=8.1. So, if anything, the M=8.1 turned off for a week or more the region that ruptured in the M=7.1. Events started turning on about 2-3 days before the M=7.1, but none of those struck within 40 km of the future M=7.1 mainshock. The seismic surface waves unleashed by great earthquakes envelop the globe in just 160 minutes, and yet triggering of remote large aftershocks during these 2-3 hours is either very rare [Pollitz et al., Nature 2012] or in dispute [Fan & Shearer, 2016 vs. Yue et al., 2017]. So, the waves must trigger tiny shocks that cascade into larger shocks after some delay. Or, perhaps the stresses conveyed by the waves pump pockets of fluids that slowly diffuse into nearby fault zones, lubricating them to the point of failure [Parsons at al., 2017]. In the cases where great earthquakes are indisputably seen to trigger aftershocks at great distances or even globally, they to do so within several days, or a week at most. Since Puebla struck 12 days later, this seems to us too long a period to be explained by dynamic triggering. Even though neither quake on their own is rare, what's the chance of independent M=8.1 and M=7.1 events just 12

Anti-Ma2 antibody related paraneoplastic limbic/brain stem encephalitis associated with breast cancer expressing Ma1, Ma2, and Ma3 mRNAs.

Science.gov (United States)

Sahashi, K; Sakai, K; Mano, K; Hirose, G

2003-09-01

A 69 year old woman presented with cognitive impairment and supranuclear gaze palsy caused by paraneoplastic limbic/brain stem encephalitis associated with atypical medullary breast carcinoma. The cerebrospinal fluid from the patient harboured an anti-neuronal cell antibody against Ma2 antigen, but not against Ma1 or Ma3 antigen. Despite the antibody being restricted to the Ma2 antigen, the patient's cancer tissue expressed Ma1, Ma2, and Ma3 mRNAs. These results, and the expression of Ma2 mRNA in an atypical medullar breast carcinoma in another patient without paraneoplastic encephalitis, indicate that the induction of anti-Ma2 antibody depends on host immunoreponsiveness and not on the presence of the antigen itself in the cancer.

Differential regulation by agonist and phorbol ester of cloned m1 and m2 muscarinic acetylcholine receptors in mouse Y1 adrenal cells and in Y1 cells deficient in cAMP-dependent protein kinase

International Nuclear Information System (INIS)

Scherer, N.M.; Nathanson, N.M.

1990-01-01

Cloned muscarinic acetylcholine m1 and m2 receptors were expressed in stably transfected mouse Y1 adrenal cells and in a variant Y1 line, Kin-8, which is deficient in cAMP-dependent protein kinase activity (PKA - ). m1 and m2 receptors were rapidly internalized following exposure of transfected PKA + or PKA - cells to the muscarinic agonist carbachol. Thus, agonist-dependent internalization of m1 and m2 did not require PKA activity. A differential effect of PKA on regulation by agonist of the m2 receptor, but not the m1 receptor, was unmasked in PKA - cells. These data indicate that the basal activity of PKA may modulate the agonist-dependent internalization of the m2 receptor, but not the m1 receptor. The internalization of the m1 and m2 receptors in both PKA + and PKA - cells was accompanied by desensitization of functional responses. Exposure of PKA + cells to 10 -7 M phorbol 12-myristate 13-acetate (PMA), an activator of protein kinase C, resulted in a 30 ± 9% decrease in the number of m1 receptors on the cell surface. The m2 receptor was not internalized following treatment of either PKA + or PKA - cells with PMA. Thus, the m1 and m2 receptors show differential sensitivity to internalization by PMA. Agonist-dependent internalization of the m1 receptor appeared to be independent of activation of PKC because (1) agonist-dependent internalization of m1 was not attenuated in PKA - cells, (2) the rate and extent of internalization of m1 in cells exposed to PMA were less than those in cells exposed to agonist, and (3) treatment of cells with concanavalin A selectivity blocked internalization of m1 in cells exposed to PMA, but not to agonist. The effects of agonist and PMA on receptor internalization were not additive. Exposure of PKA + or PKA - cells to PMA reduced the magnitude of pilocarpine-stimulated PI hydrolysis by about 25%

Observations of M dwarfs beyond 2.2 μm

International Nuclear Information System (INIS)

Berriman, G.

1987-01-01

This paper presents the first systematic spectroscopic observations of M dwarfs beyond 2.2μm. The coolest dwarfs show strong water absorption in the 3μm window, and beyond 4μm, the energy distributions of all the stars fall slightly less steeply than the Rayleigh-Jeans tail of a blackbody. Spectra between 1 and 4μm are essential in deriving accurate luminosities of M dwarfs, and possibly in deriving accurate effective temperatures too. New values reported here are not in general well explained by theoretical models of hydrogen burning stars. This is especially true for those cooler than 3000K: in the HR diagram they lie closer to brown dwarfs, in contrast to recent results based only on photometry. (author)

Mistletoes and epiphytic lichens contribute to litter input in Nothofagus antarctica forests

Science.gov (United States)

Soler, Rosina; Pastur, Guillermo Martínez; Lencinas, María Vanessa; Peri, Pablo Luis

2015-10-01

Litter input is one of the key components that define nutrient cycling in forests and the majority of studies only consider the tree components of litterfall. However, epiphytic species can play a crucial role in litter input throughout the growing season. This work evaluates changes in litter production by mistletoe (Misodendrum sp.) and epiphytic lichen (Usnea sp.), related to crown cover in mature unmanaged, second-growth and managed (thinned for silvopastoral use) forests in Tierra del Fuego (Argentina). We used plastic traps to collect litterfall biomass from trees, lichens and mistletoes on a monthly basis over three consecutive years. Tree litter was considerable during autumn (March to May), which is typical of Nothofagus deciduous species in the Southern hemisphere. In contrast, peak litterfall from mistletoes and lichens occurred during spring and summer seasons. Tree litter (1954-3398 kg dry matter ha-1 year-1) was correlated with crown cover gradient being highest in second-growth forests and lowest in thinned sites. While litter input from mistletoes did not vary among forest types (307-333 kg dry matter ha-1 year-1), lichen litter (11-40 kg dry matter ha-1 year-1) was higher in unmanaged and thinned mature forests despite differences in tree crown cover. Contrary to what we expected, the management practices investigated here did not affect the biomass of canopy communities compared to unmanaged mature forests. Mistletoes and lichens significantly increased the spatial (forest type) and temporal complexity (extended period of falling) of litterfall in Nothofagus antarctica forests. This study provides a starting point to understand the ecological relevance of canopy communities in the Patagonian forests of southern Argentina.

Spontaneous transition rates for electric dipole (E1), magnetic dipole (M1), electric quadrupole (E2) and magnetic quadrupole (M2) transitions for He-like calcium and sulfur ions

International Nuclear Information System (INIS)

Kingston, A.E.; Norrington, P.H.; Boone, A.W.

2002-01-01

The spontaneous decay rates for the electric dipole (E1), electric quadrupole (E2), magnetic dipole (M1) and magnetic quadrupole (M2) transitions between all of the 1s 2 , 1s2 l and 1s3 l states have been obtained for helium-like calcium and sulfur ions. To assess the accuracy of the calculations, the transition probabilities were calculated using two sets of configuration interaction wavefunctions. One set of wavefunctions was generated using the fully relativistic GRASP code and the other was obtained using CIV3, in which relativistic effects are introduced using the Breit-Pauli approximation. The transition rates, A values, oscillator strengths and line strengths from our two calculations are found to be similar and to compare very well with other recent results for Δn=1 or 2 transitions. For Δn=0 transitions the agreement is much less good; this is mainly due to differences in the calculated excitation energies. (author)

The MAP, M/G1,G2/1 queue with preemptive priority

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Bong Dae Choi

1997-01-01

Full Text Available We consider the MAP, M/G1,G2/1 queue with preemptive resume priority, where low priority customers arrive to the system according to a Markovian arrival process (MAP and high priority customers according to a Poisson process. The service time density function of low (respectively: high priority customers is g1(x (respectively: g2(x. We use the supplementary variable method with Extended Laplace Transforms to obtain the joint transform of the number of customers in each priority queue, as well as the remaining service time for the customer in service in the steady state. We also derive the probability generating function for the number of customers of low (respectively, high priority in the system just after the service completion epochs for customers of low (respectively, high priority.

Classification of acute myeloid leukemia subtypes M1, M2 and M3 using active contour without edge segmentation and momentum backpropagation artificial neural network

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Harjoko Agus

2018-01-01

Full Text Available Acute Myeloid Leukemia (AML is a type of cancer which attacks white blood cells from myeloid. AML has eight subtypes, namely: M0, M1, M2, M3, M4, M5, M6, and M7. AML subtypes M1, M2 and M3 are affected by the same type of cells, myeloblast, making it needs more detailed analysis to distinguish. To overcome these obstacles, this research is applying digital image processing with Active Contour Without Edge (ACWE and Momentum Backpropagation artificial neural network for AML subtypes M1, M2 and M3 classification based on the type of the cell. Six features required as training parameters from every cell obtained by using feature extraction. The features are: cell area, perimeter, circularity, nucleus ratio, mean and standard deviation. The results show that ACWE can be used for segmenting white blood cells with 83.789% success percentage of 876 total cell objects. The whole AML slides had been identified according to the cell types predicted number through training with momentum backpropagation. Five times testing calibration with the best parameter generated averages value of 84.754% precision, 75.887% sensitivity, 95.090% specificity and 93.569% accuracy.

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

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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.

Estructura y dinámica del manglar del delta del río Ranchería, Caribe colombiano

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Luisa Fernanda Lema Vélez

2007-03-01

Full Text Available Se estudió de la supervivencia de plántulas y aumento de biomasa de Rhizophora mangle L., Avicennia germinans L. y Laguncularia racemosa (L. Gaertn. f., principales especies de manglar del delta del río Ranchería, Colombia. Se encontró supervivencia de plántulas sólo de R. mangle. Se cuantificó también la tasa máxima de caída de hojarasca en el bosque; este valor se interpoló dentro de una regresión exponencial elaborada a partir valores máximos y anuales publicados en diferentes fuentes, y se halló un valor anual de 12.9 mgha-1a-1. A partir ecuaciones alométricas elaboradas para la zona y otras de fuentes secundarias puede calcularse un aumento de biomasa en 7.4 mgha-1a-1. La productividad del manglar del río Ranchería (20.2 mgha¹a-1 está representada en su mayoría por caída de hojarasca. Consideramos que esta productividad es alta para un bosque sometido a condiciones naturales y antrópicas tan desfavorables, como son la extrema estacionalidad y el continuo forrajeo de ganado ovino y caprino. Suponemos que la alta productividad se trata precisamente de una respuesta de la vegetación a la tensión ambiental.Structure and dynamics of the mangrove forest in the Ranchería river delta, Colombian Caribbean. We registered seedling survival and biomass increase for Rhizophora mangle L., Avicennia germinans L. and Laguncularia racemosa (L. Gaertn. f., main mangrove species in the Rancheria River delta, Colombia. Only seedlings of R. mangle were found to survive. We also measured maximum rate of litterfall. We estimated annual litterfall through interpolation within an exponential regression performed with maximum and annual litterfall data published in other sources; the value of annual litterfall for the area was estimated to be 12.9 mgha-1y-1. We found a 7.4 mgha-1y-1 increase in biomass. Litterfall constitutes the larger fraction of the 20.2 mgha-1y-1 productivity of this mangrove. We believe this is a very high value for a

M2 macrophages coexist with a Th1-driven profile in periapical cysts.

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Ribeiro, C M; de Carli, M L; Nonogaki, S; Nogueira, D A; Pereira, A A C; Sperandio, F F; Hanemann, J A C

2018-02-01

To evaluate the participation of both Th1 and Th2 responses in periapical cysts by assessing the presence of M2 macrophages, as well as acute IL-1 β, TNF-α and IL-6 cytokines. Twenty-four cases of periapical cysts were selected. Immuno-expressions of IL-1 β, IL-6, TNF-α and CD163 were analysed in the cystic capsules in both superficial and deeper regions. Data were analysed with paired Wilcoxon test and Spearman correlation coefficient (P ≤ 0.05). There was a higher expression of IL-1β, IL-6, TNF-α and M2 macrophages in the superficial region (P periapical cysts and correlated with the expression of certain acute Th1-related cytokines. This illustrates the coexistence of an acute and chronic Th2-driven immune response in these lesions. Although M2 macrophages favour the healing process, their presence is not sufficient for periapical cyst regression, once an acute active response has occurred due to an infectious stimuli. © 2017 International Endodontic Journal. Published by John Wiley & Sons Ltd.

Alternatively Activated (M2) Macrophage Phenotype Is Inducible by Endothelin-1 in Cultured Human Macrophages.

Science.gov (United States)

Soldano, Stefano; Pizzorni, Carmen; Paolino, Sabrina; Trombetta, Amelia Chiara; Montagna, Paola; Brizzolara, Renata; Ruaro, Barbara; Sulli, Alberto; Cutolo, Maurizio

2016-01-01

Alternatively activated (M2) macrophages are phenotypically characterized by the expression of specific markers, mainly macrophage scavenger receptors (CD204 and CD163) and mannose receptor-1 (CD206), and participate in the fibrotic process by over-producing pro-fibrotic molecules, such as transforming growth factor-beta1 (TGFbeta1) and metalloproteinase (MMP)-9. Endothelin-1 (ET-1) is implicated in the fibrotic process, exerting its pro-fibrotic effects through the interaction with its receptors (ETA and ETB). The study investigated the possible role of ET-1 in inducing the transition from cultured human macrophages into M2 cells. Cultured human monocytes (THP-1 cell line) were activated into macrophages (M0 macrophages) with phorbol myristate acetate and subsequently maintained in growth medium (M0-controls) or treated with either ET-1 (100nM) or interleukin-4 (IL-4, 10ng/mL, M2 inducer) for 72 hours. Similarly, primary cultures of human peripheral blood monocyte (PBM)-derived macrophages obtained from healthy subjects, were maintained in growth medium (untreated cells) or treated with ET-1 or IL-4 for 6 days. Both M0 and PBM-derived macrophages were pre-treated with ET receptor antagonist (ETA/BRA, bosentan 10-5M) for 1 hour before ET-1 stimulation. Protein and gene expression of CD204, CD206, CD163, TGFbeta1 were analysed by immunocytochemistry, Western blotting and quantitative real time polymerase chain reaction (qRT-PCR). Gene expression of interleukin(IL)-10 and macrophage derived chemokine (CCL-22) was evaluated by qRT-PCR. MMP-9 production was investigated by gel zymography. ET-1 significantly increased the expression of M2 phenotype markers CD204, CD206, CD163, IL-10 and CCL-22, and the production of MMP-9 in both cultures of M0 and PBM-derived macrophages compared to M0-controls and untreated cells. In cultured PBM-derived macrophages, ET-1 increased TGFbeta1 protein and gene expression compared to untreated cells. The ET-1-mediated effects were

ERK1/2 signaling plays an important role in topoisomerase II poison-induced G2/M checkpoint activation.

Science.gov (United States)

Kolb, Ryan H; Greer, Patrick M; Cao, Phu T; Cowan, Kenneth H; Yan, Ying

2012-01-01

Topo II poisons, which target topoisomerase II (topo II) to generate enzyme mediated DNA damage, have been commonly used for anti-cancer treatment. While clinical evidence demonstrate a capability of topo II poisons in inducing apoptosis in cancer cells, accumulating evidence also show that topo II poison treatment frequently results in cell cycle arrest in cancer cells, which was associated with subsequent resistance to these treatments. Results in this report indicate that treatment of MCF-7 and T47D breast cancer cells with topo II poisons resulted in an increased phosphorylation of extracellular signal-regulated kinase 1 and 2 (ERK1/2) and an subsequent induction of G2/M cell cycle arrest. Furthermore, inhibition of ERK1/2 activation using specific inhibitors markedly attenuated the topo II poison-induced G2/M arrest and diminished the topo II poison-induced activation of ATR and Chk1 kinases. Moreover, decreased expression of ATR by specific shRNA diminished topo II poison-induced G2/M arrest but had no effect on topo II poison-induced ERK1/2 activation. In contrast, inhibition of ERK1/2 signaling had little, if any, effect on topo II poison-induced ATM activation. In addition, ATM inhibition by either incubation of cells with ATM specific inhibitor or transfection of cells with ATM specific siRNA did not block topo II poison-induced G2/M arrest. Ultimately, inhibition of ERK1/2 signaling greatly enhanced topo II poison-induced apoptosis. These results implicate a critical role for ERK1/2 signaling in the activation of G2/M checkpoint response following topo II poison treatment, which protects cells from topo II poison-induced apoptosis.

CO2 line-mixing database and software update and its tests in the 2.1 μm and 4.3 μm regions

International Nuclear Information System (INIS)

Lamouroux, J.; Régalia, L.; Thomas, X.; Vander Auwera, J.; Gamache, R.R.; Hartmann, J.-M.

2015-01-01

An update of the former version of the database and software for the calculation of CO 2 –air absorption coefficients taking line-mixing into account [Lamouroux et al. J Quant Spectrosc Radiat Transf 2010;111:2321] is described. In this new edition, the data sets were constructed using parameters from the 2012 version of the HITRAN database and recent measurements of line-shape parameters. Among other improvements, speed-dependent profiles can now be used if line-mixing is treated within the first order approximation. This new package is tested using laboratory spectra measured in the 2.1 μm and 4.3 μm spectral regions for various pressures, temperatures and CO 2 concentration conditions. Despite improvements at 4.3 μm at room temperature, the conclusions on the quality of this update are more ambiguous at low temperature and in the 2.1 μm region. Further tests using laboratory and atmospheric spectra are thus required for the evaluation of the performances of this updated package. - Highlights: • High resolution infrared spectroscopy. • CO 2 in air. • Updated tools. • Line mixing database and software

Dissociation of SERPINE1 mRNA from the translational repressor proteins Ago2 and TIA-1 upon platelet activation.

Science.gov (United States)

Corduan, Aurélie; Plé, Hélène; Laffont, Benoit; Wallon, Thérèse; Plante, Isabelle; Landry, Patricia; Provost, Patrick

2015-05-01

Platelets play an important role in haemostasis, as well as in thrombosis and coagulation processes. They harbour a wide variety of messenger RNAs (mRNAs), that can template de novo protein synthesis, and an abundant array of microRNAs, which are known to mediate mRNA translational repression through proteins of the Argonaute (Ago) family. The relationship between platelet microRNAs and proteins capable of mediating translational repression, however, remains unclear. Here, we report that half of platelet microRNAs is associated to mRNA-regulatory Ago2 protein complexes, in various proportions. Associated to these Ago2 complexes are platelet mRNAs known to support de novo protein synthesis. Reporter gene activity assays confirmed the capacity of the platelet microRNAs, found to be associated to Ago2 complexes, to regulate translation of these platelet mRNAs through their 3'UTR. Neither the microRNA repertoire nor the microRNA composition of Ago2 complexes of human platelets changed upon activation with thrombin. However, under conditions favoring de novo synthesis of Plasminogen Activator Inhibitor-1 (PAI-1) protein, we documented a rapid dissociation of the encoding platelet SERPINE1 mRNA from Ago2 protein complexes as well as from the translational repressor protein T-cell-restricted intracellular antigen-1 (TIA-1). These findings are consistent with a scenario by which lifting of the repressive effects of Ago2 and TIA-1 protein complexes, involving a rearrangement of proteinmRNA complexes rather than disassembly of Ago2microRNA complexes, would allow translation of SERPINE1 mRNA into PAI-1 in response to platelet activation.

Energies and E1, M1, E2, and M2 transition rates for states of the 2s{sup 2}2p{sup 3}, 2s2p{sup 4}, and 2p{sup 5} configurations in nitrogen-like ions between F III and Kr XXX

Energy Technology Data Exchange (ETDEWEB)

Rynkun, P., E-mail: pavel.rynkun@gmail.com [Department of Physics and Information Technologies, Lithuanian University of Educational Science, Studentu 39, LT-08106 Vilnius (Lithuania); Jönsson, P. [Group for Materials Science and Applied Mathematics, Malmö University, 20506 Malmö (Sweden); Gaigalas, G. [Department of Physics and Information Technologies, Lithuanian University of Educational Science, Studentu 39, LT-08106 Vilnius (Lithuania); Vilnius University, Institute of Theoretical Physics and Astronomy, A. Goštauto 12, LT-01108 Vilnius (Lithuania); Froese Fischer, C. [National Institute of Standards and Technology, Gaithersburg, MD 20899-8420 (United States)

2014-03-15

Based on relativistic wavefunctions from multiconfiguration Dirac–Hartree–Fock and configuration interaction calculations, E1, M1, E2, and M2 transition rates, weighted oscillator strengths, and lifetimes are evaluated for the states of the (1s{sup 2})2s{sup 2}2p{sup 3},2s2p{sup 4}, and 2p{sup 5} configurations in all nitrogen-like ions between F III and Kr XXX. The wavefunction expansions include valence, core–valence, and core–core correlation effects through single–double multireference expansions to increasing sets of active orbitals. The computed energies agree very well with experimental values, with differences of only 300–600 cm{sup −1} for the majority of the levels and ions in the sequence. Computed transitions rates are in close agreement with available data from MCHF-BP calculations by Tachiev and Froese Fischer [G.I. Tachiev, C. Froese Fischer, A and A 385 (2002) 716].

Dale Reed with model in front of M2-F1

Science.gov (United States)

1967-01-01

Dale Reed with a model of the M2-F1 in front of the actual lifting body. Reed used the model to show the potential of the lifting bodies. He first flew it into tall grass to test stability and trim, then hand-launched it from buildings for longer flights. Finally, he towed the lifting-body model aloft using a powered model airplane known as the 'Mothership.' A timer released the model and it glided to a landing. Dale's wife Donna used a 9 mm. camera to film the flights of the model. Its stability as it glided--despite its lack of wings--convinced Milt Thompson and some Flight Research Center engineers including the center director, Paul Bikle, that a piloted lifting body was possible. The lifting body concept evolved in the mid-1950s as researchers considered alternatives to ballistic reentries of piloted space capsules. The designs for hypersonic, wingless vehicles were on the boards at NASA Ames and NASA Langley facilities, while the US Air Force was gearing up for its Dyna-Soar program, which defined the need for a spacecraft that would land like an airplane. Despite favorable research on lifting bodies, there was little support for a flight program. Dryden engineer R. Dale Reed was intrigued with the lifting body concept, and reasoned that some sort of flight demonstration was needed before wingless aircraft could be taken seriously. In February 1962, he built a model lifting body based upon the Ames M2 design, and air-launched it from a radio controlled 'mothership.' Home movies of these flights, plus the support of research pilot Milt Thompson, helped pursuade the facilities director, Paul Bikle, to give the go-ahead for the construction of a full-scale version, to be used as a wind-tunnel model and possibly flown as a glider. Comparing lifting bodies to space capsules, an unofficial motto of the project was, 'Don't be Rescued from Outer Space--Fly Back in Style.' The construction of the M2-F1 was a joint effort by Dryden and a local glider manufacturer, the

Absolute M1 and E2 Transition Probabilities in 233U

International Nuclear Information System (INIS)

Malmskog, S.G.; Hoejeberg, M.

1967-08-01

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

Thermodynamic properties of CuCr/sub 2/S/sub 4/ solid solutions in Cusub(1/2)Msub(1/2) Crsub(2)Ssub(4) (M - Ga, In)

Energy Technology Data Exchange (ETDEWEB)

Titov, V.V.; Kesler, Ya.A.; Shelkotunov, V.A.; Gordeev, I.V.; Tret' yakov, Yu.D.

1985-04-01

By means of an adiabatic calorimeter and quartz dilatometer for CuCr/sub 2/S/sub 4/ in Cusub(1/2)Msub(1/2) Crsub(2)Ssub(4) (M-Ga, In) temperature dependences of heat capacity are determined. The contribution of various components into heat capacity is estimated, thermodynamic parameters of magnetic transformation are calculated.

Preclinical characterization of OSI-027, a potent and selective inhibitor of mTORC1 and mTORC2: distinct from rapamycin.

Science.gov (United States)

Bhagwat, Shripad V; Gokhale, Prafulla C; Crew, Andrew P; Cooke, Andy; Yao, Yan; Mantis, Christine; Kahler, Jennifer; Workman, Jennifer; Bittner, Mark; Dudkin, Lorina; Epstein, David M; Gibson, Neil W; Wild, Robert; Arnold, Lee D; Houghton, Peter J; Pachter, Jonathan A

2011-08-01

The phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway is frequently activated in human cancers, and mTOR is a clinically validated target. mTOR forms two distinct multiprotein complexes, mTORC1 and mTORC2, which regulate cell growth, metabolism, proliferation, and survival. Rapamycin and its analogues partially inhibit mTOR through allosteric binding to mTORC1, but not mTORC2, and have shown clinical utility in certain cancers. Here, we report the preclinical characterization of OSI-027, a selective and potent dual inhibitor of mTORC1 and mTORC2 with biochemical IC(50) values of 22 nmol/L and 65 nmol/L, respectively. OSI-027 shows more than 100-fold selectivity for mTOR relative to PI3Kα, PI3Kβ, PI3Kγ, and DNA-PK. OSI-027 inhibits phosphorylation of the mTORC1 substrates 4E-BP1 and S6K1 as well as the mTORC2 substrate AKT in diverse cancer models in vitro and in vivo. OSI-027 and OXA-01 (close analogue of OSI-027) potently inhibit proliferation of several rapamycin-sensitive and -insensitive nonengineered and engineered cancer cell lines and also, induce cell death in tumor cell lines with activated PI3K-AKT signaling. OSI-027 shows concentration-dependent pharmacodynamic effects on phosphorylation of 4E-BP1 and AKT in tumor tissue with resulting tumor growth inhibition. OSI-027 shows robust antitumor activity in several different human xenograft models representing various histologies. Furthermore, in COLO 205 and GEO colon cancer xenograft models, OSI-027 shows superior efficacy compared with rapamycin. Our results further support the important role of mTOR as a driver of tumor growth and establish OSI-027 as a potent anticancer agent. OSI-027 is currently in phase I clinical trials in cancer patients. ©2011 AACR

Genetic and epigenetic inactivation of SESTRIN1 controls mTORC1 and response to EZH2 inhibition in follicular lymphoma.

Science.gov (United States)

Oricchio, Elisa; Katanayeva, Natalya; Donaldson, Maria Christine; Sungalee, Stephanie; Pasion, Joyce P; Béguelin, Wendy; Battistello, Elena; Sanghvi, Viraj R; Jiang, Man; Jiang, Yanwen; Teater, Matt; Parmigiani, Anita; Budanov, Andrei V; Chan, Fong Chun; Shah, Sohrab P; Kridel, Robert; Melnick, Ari M; Ciriello, Giovanni; Wendel, Hans-Guido

2017-06-28

Follicular lymphoma (FL) is an incurable form of B cell lymphoma. Genomic studies have cataloged common genetic lesions in FL such as translocation t(14;18), frequent losses of chromosome 6q, and mutations in epigenetic regulators such as EZH2 Using a focused genetic screen, we identified SESTRIN1 as a relevant target of the 6q deletion and demonstrate tumor suppression by SESTRIN1 in vivo. Moreover, SESTRIN1 is a direct target of the lymphoma-specific EZH2 gain-of-function mutation ( EZH2 Y641X ). SESTRIN1 inactivation disrupts p53-mediated control of mammalian target of rapamycin complex 1 (mTORC1) and enables mRNA translation under genotoxic stress. SESTRIN1 loss represents an alternative to RRAGC mutations that maintain mTORC1 activity under nutrient starvation. The antitumor efficacy of pharmacological EZH2 inhibition depends on SESTRIN1, indicating that mTORC1 control is a critical function of EZH2 in lymphoma. Conversely, EZH2 Y641X mutant lymphomas show increased sensitivity to RapaLink-1, a bifunctional mTOR inhibitor. Hence, SESTRIN1 contributes to the genetic and epigenetic control of mTORC1 in lymphoma and influences responses to targeted therapies. Copyright © 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.

Complications and 2-year valve survival following Ahmed valve implantation during the first 2 years of life.

Science.gov (United States)

Almobarak, F; Al-Mobarak, F; Khan, A O

2009-06-01

To report complications and 2-year valve survival following Ahmed valve implantation during the first 2 years of life. Retrospective institutional case series. Forty-two eyes of 36 patients with Ahmed valve implantation (without prior drainage device surgery) during the first 2 years of life and 2 years' postsurgical follow-up were identified. Most eyes had primary congenital glaucoma (28/42, 66.7%), aphakic glaucoma (5/42, 11.9%) or Peters anomaly (5/42, 11.9%). All but three eyes had prior ocular surgery. Surgery was at a mean age of 11.83 months (m) (SD 5.63). The most common significant postoperative complications were tube malpositioning requiring intervention (11/42, 26.2%), endophthalmitis (3/42, 7.1%; one with tube exposure) and retinal detachment (3/42, 7.1%). Thirty-six eyes (85.8%) required resumption of antiglaucoma medications to maintain intraocular pressure (IOP) valve survival (IOPendophthalmitis and retinal detachment are known potential complications following any incisional surgery for advanced buphthalmos; however, tube exposure is a unique potential problem following aqueous shunt implantation that can lead to intraocular infection. Cumulative valve survival 2 years following implantation was 63.3%.

Mitofusin 1 is degraded at G2/M phase through ubiquitylation by MARCH5

Directory of Open Access Journals (Sweden)

Park Yong-Yea

2012-12-01

Full Text Available Abstract Background Mitochondria exhibit a dynamic morphology in cells and their biogenesis and function are integrated with the nuclear cell cycle. In mitotic cells, the filamentous network structure of mitochondria takes on a fragmented form. To date, however, whether mitochondrial fusion activity is regulated in mitosis has yet to be elucidated. Findings Here, we report that mitochondria were found to be fragmented in G2 phase prior to mitotic entry. Mitofusin 1 (Mfn1, a mitochondrial fusion protein, interacted with cyclin B1, and their interactions became stronger in G2/M phase. In addition, MARCH5, a mitochondrial E3 ubiquitin ligase, reduced Mfn1 levels and the MARCH5-mediated Mfn1 ubiquitylation were enhanced in G2/M phase. Conclusions Mfn1 is degraded through the MARCH5-mediated ubiquitylation in G2/M phase and the cell cycle-dependent degradation of Mfn1 could be facilitated by interaction with cyclin B1/Cdk1 complexes.

OPEC/OJEC for stage 4 neuroblastoma in children over 1 year of age.

Science.gov (United States)

Tweddle, D A; Pinkerton, C R; Lewis, I J; Ellershaw, C; Cole, M; Pearson, A D

2001-01-01

This paper reports the toxicity of OPEC/OJEC chemotherapy in stage 4 neuroblastoma patients over 1 year of age. Ninety-five patients with stage 4 neuroblastoma received alternating courses of OPEC/OJEC--vincristine 1.5 mg/m2 (O), cisplatin 80 mg/m2 (P), etoposide 200 mg/m2 (E), cyclophosphamide 600 mg/m2 (C), and carboplatin 500 mg/m2 (J), every 21 days if there was haematological recovery. Seventy out of ninety-five (74%) patients completed seven or more courses and were evaluable for toxicity. Of these 70 patients, 33% had more than three episodes of fever and sepsis, 35% required more than five blood or platelet transfusions, 36% had grade 2 or more gastrointestinal toxicity and 9% had neurotoxicity. There was a median reduction in GFR of 32 ml/min/1.73 m2 (-46 to 134) and there was one toxic death. OPEC/OJEC is a well-tolerated therapy for stage 4 neuroblastoma over 1 year of age.

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.

Two distinct mTORC2-dependent pathways converge on Rac1 to drive breast cancer metastasis.

Science.gov (United States)

Morrison Joly, Meghan; Williams, Michelle M; Hicks, Donna J; Jones, Bayley; Sanchez, Violeta; Young, Christian D; Sarbassov, Dos D; Muller, William J; Brantley-Sieders, Dana; Cook, Rebecca S

2017-06-30

The importance of the mTOR complex 2 (mTORC2) signaling complex in tumor progression is becoming increasingly recognized. HER2-amplified breast cancers use Rictor/mTORC2 signaling to drive tumor formation, tumor cell survival and resistance to human epidermal growth factor receptor 2 (HER2)-targeted therapy. Cell motility, a key step in the metastatic process, can be activated by mTORC2 in luminal and triple negative breast cancer cell lines, but its role in promoting metastases from HER2-amplified breast cancers is not yet clear. Because Rictor is an obligate cofactor of mTORC2, we genetically engineered Rictor ablation or overexpression in mouse and human HER2-amplified breast cancer models for modulation of mTORC2 activity. Signaling through mTORC2-dependent pathways was also manipulated using pharmacological inhibitors of mTOR, Akt, and Rac. Signaling was assessed by western analysis and biochemical pull-down assays specific for Rac-GTP and for active Rac guanine nucleotide exchange factors (GEFs). Metastases were assessed from spontaneous tumors and from intravenously delivered tumor cells. Motility and invasion of cells was assessed using Matrigel-coated transwell assays. We found that Rictor ablation potently impaired, while Rictor overexpression increased, metastasis in spontaneous and intravenously seeded models of HER2-overexpressing breast cancers. Additionally, migration and invasion of HER2-amplified human breast cancer cells was diminished in the absence of Rictor, or upon pharmacological mTOR kinase inhibition. Active Rac1 was required for Rictor-dependent invasion and motility, which rescued invasion/motility in Rictor depleted cells. Rictor/mTORC2-dependent dampening of the endogenous Rac1 inhibitor RhoGDI2, a factor that correlated directly with increased overall survival in HER2-amplified breast cancer patients, promoted Rac1 activity and tumor cell invasion/migration. The mTORC2 substrate Akt did not affect RhoGDI2 dampening, but partially

Persistent genital herpes simplex virus-2 shedding years following the first clinical episode.

Science.gov (United States)

Phipps, Warren; Saracino, Misty; Magaret, Amalia; Selke, Stacy; Remington, Mike; Huang, Meei-Li; Warren, Terri; Casper, Corey; Corey, Lawrence; Wald, Anna

2011-01-15

Patients with newly acquired genital herpes simplex virus 2 (HSV-2) infection have virus frequently detected at the genital mucosa. Rates of genital shedding initially decrease over time after infection, but data on long-term viral shedding are lacking. For this study, 377 healthy adults with history of symptomatic genital HSV-2 infection collected anogenital swabs for HSV-2 DNA polymerase chain reaction for at least 30 consecutive days. Time since first genital herpes episode was significantly associated with reduced genital shedding. Total HSV shedding occurred on 33.6% of days in participants <1 year, 20.6% in those 1-9 years, and 16.7% in those ≥10 years from first episode. Subclinical HSV shedding occurred on 26.2% of days among participants <1 year, 13.1% in those 1-9 years, and 9.3% in those ≥10 years from first episode. On days with HSV detection, mean quantity was 4.9 log₁₀ copies/mL for those <1 year, 4.7 log₁₀ copies/mL among those 1-9 years, and 4.6 log₁₀ copies/mL among those ≥10 years since first episode. Rates of total and subclinical HSV-2 shedding decrease after the first year following the initial clinical episode. However, viral shedding persists at high rates and copy numbers years after infection, and therefore may pose continued risk of HSV-2 transmission to sexual partners.

Análise comparativa da produção de serapilheira em fragmentos arbóreos e arbustivos em área de caatinga na FLONA de Açu-RN Comparative analysis of litter production in shrub-trees fragments in a caatinga area of FLONA Açu-RN

Directory of Open Access Journals (Sweden)

Caio César de Azevedo Costa

2010-04-01

Full Text Available A serapilheira compreende a camada mais superficial do solo em ambientes florestais, sendo formada por folhas, ramos, órgãos reprodutivos e detritos, que exercem inúmeras funções no equilíbrio e dinâmica dos ecossistemas florestais. O objetivo deste trabalho foi avaliar a produção de serapilheira em ambientes arbóreo e arbustivo em uma área preservada no bioma Caatinga. A pesquisa foi realizada na Floresta Nacional do Açu-RN, a qual foi dividida em dois setores distintos, um setor arbóreo e outro arbustivo. Foram realizadas 12 coletas mensais da serapilheira. Em cada um dos setores, foram instalados 20 coletores de madeira medindo 1,0 m x 1,0 m x 0,15 m (0,15 m³ e com fundo de tela de náilon de malha 1 mm, distribuídos de forma aleatória na área da Flona. O material coletado foi acondicionado em sacos de papel, identificado e conduzido ao Laboratório Zoobotânico da UERN. O material foi secado em estufa de circulação de ar forçada a 70 ºC durante 72 h. As médias de todas as variáveis foram expressas em g/m² e submetidas à análise de variância e ao teste t (pThe litter is the most superficial layer of soil in a forest environment, it's composed by Leaves, Twigs, seeds, roots and remains, which together have innumerous importance in establishing and balancing the ecosystem. The purpose of this work was to evaluate the litterfall in two different areas, shrubs and treed, in a preserved area of biom caatinga. This research was carried out in the Açu Nacional Forest - FLONA/ AÇÚ-RN. The FLONA was divided in two different areas, in relation to aspects and vegetation postage, for shrubs and trees. 12 litter collections were made. Each area had 20 wooden traps installed measuring 1.0m X 1.0m X 0.15m (0.15m3, with 1mm nylon mesh, distributed at random in the Flona's area. The material collected was put in paper bags, named and taken to the UERN botanic lab. The material was oven-dried at 70º C during 72h and weighed. The

M-shell ionization of heavy elements by 0.1-1.0 MeV/amu 1,2H and 3,4He ions

International Nuclear Information System (INIS)

Pajek, M.; Banas, D.; Braziewicz, J.; Czarnota, M.; Bienkowski, A.; Jaskola, M.; Korman, A.; Trautmann, D.; Lapicki, G.

2006-01-01

The M-shell ionization in high-Z atoms by low-energy light 1 1 H, 1 2 H, 2 3 He, and 2 4 He ions have been studied systematically in the energy range 0.1-1.0 MeV/amu in order to verify the available theoretical approaches describing the M-shell ionization by charged particles in asymmetric collisions. The present low-energy data, combined with our earlier results reported for M-shell ionization by hydrogen and helium ions for higher energies, form a systematic experimental basis to test the theoretical predictions of M-shell ionization based on the plane-wave Born approximation (PWBA), the semiclassical approximation (SCA), and the binary-encounter approximation (BEA). In the PWBA based approaches the energy loss (E), Coulomb deflection (C), perturbed stationary state (PSS), and relativistic (R) effects were considered within the ECPSSR theory and its recent modification, called the ECUSAR theory, in which a description of the PSS effect was corrected to account for the united- and separated-atom (USA) electron binding energy limits. In the SCA calculations with relativistic wave functions the binding effect was included only in the limiting cases of separated-atom and united-atom limits. Possible contribution of the electron capture, multiple ionization, and recoil ionization to the M-shell vacancy production, which is dominated for light ions impact by direct single ionization process, are also discussed. The universal scaling of measured M-shell x-ray production and ionization cross sections was investigated in detail. Using the present data the isotopic effect has been studied by comparing the measured M-shell ionization cross-section ratios for equal-velocity hydrogen 1 1 H and 1 2 H as well as helium 2 3 He and 2 4 He isotopes. In addition, the ratios of measured ionization cross sections for 1 2 H and 2 4 He were used to investigate the role of the binding effect. The present results are of practical importance for the application of particle-induced x

Dual mTORC1/C2 inhibitors suppress cellular geroconversion (a senescence program).

Science.gov (United States)

Leontieva, Olga V; Demidenko, Zoya N; Blagosklonny, Mikhail V

2015-09-15

In proliferating cells, mTOR is active and promotes cell growth. When the cell cycle is arrested, then mTOR converts reversible arrest to senescence (geroconversion). Rapamycin and other rapalogs suppress geroconversion, maintaining quiescence instead. Here we showed that ATP-competitive kinase inhibitors (Torin1 and PP242), which inhibit both mTORC1 and TORC2, also suppressed geroconversion. Despite inhibition of proliferation (in proliferating cells), mTOR inhibitors preserved re-proliferative potential (RP) in arrested cells. In p21-arrested cells, Torin 1 and PP242 detectably suppressed geroconversion at concentrations as low as 1-3 nM and 10-30 nM, reaching maximal gerosuppression at 30 nM and 300 nM, respectively. Near-maximal gerosuppression coincided with inhibition of p-S6K(T389) and p-S6(S235/236). Dual mTOR inhibitors prevented senescent morphology and hypertrophy. Our study warrants investigation into whether low doses of dual mTOR inhibitors will prolong animal life span and delay age-related diseases. A new class of potential anti-aging drugs can be envisioned.

IL-2/anti-IL-2 mAb immunocomplexes: A renascence of IL-2 in cancer immunotherapy?

Czech Academy of Sciences Publication Activity Database

Tomala, Jakub; Kovář, Marek

2016-01-01

Roč. 5, č. 3 (2016), e1102829 ISSN 2162-402X R&D Projects: GA ČR GA13-12885S; GA MŠk(CZ) ED1.1.00/02.0109 Institutional support: RVO:61388971 Keywords : Anti-IL-2 mAb * cancer immunotherapy * IL-2 Subject RIV: EE - Microbiology, Virology Impact factor: 7.719, year: 2016

Magnetic ordering of quasi-1 D S=1/2 Heisenberg antiferromagnet Cu benzoate at sub-mK temperatures

International Nuclear Information System (INIS)

Karaki, Y.; Masutomi, R.; Kubota, M.; Ishimoto, H.; Asano, T.; Ajiro, Y.

2003-01-01

We have measured the AC susceptibility of quasi-1D S=1/2 Heisenberg antiferromagnet Cu benzoate at temperatures down to 0.2 mK. A sharp susceptibility peak is observed at 0.8 mK under an earth field. This fact indicates a 3D ordering of linear chains coupled by a weak magnetic interaction between chains

Nanocrystals of the quaternary thermoelectric materials: AgPb{sub m}SbTe{sub m+2}(m=1-18): Phase-segregated or solid solutions?

Energy Technology Data Exchange (ETDEWEB)

Arachchige, Indika U [Department of Chemistry, Northwestern University Evanston, IL (United States); Wu, Jinsong; Dravid, Vinayak P [Department of Materials Science and Engineering, Northwestern University Evanston, IL (United States); Kanatzidis, Mercouri G [Department of Chemistry, Northwestern University Evanston, IL (United States); Material Science Division, Argonne National Laboratory Argonne, IL (United States)

2008-10-02

Facile synthesis of a series of thermoelectrically relevant AgPb{sub m}SbTe{sub m+2}(m=1-18) nanoparticles is carried out by using a colloidal synthetic route. As-synthesized nanocrystals are spherical in geometry and adopt a cubic NaCl-type structure. These quaternary nanocrystals behave as solid solutions at room temperature and tend to phase separate into AgSbTe{sub 2} and PbTe upon annealing at moderately high temperature. (Abstract Copyright [2008], Wiley Periodicals, Inc.)

mTOR complex 2 phosphorylates IMP1 cotranslationally to promote IGF2 production and the proliferation of mouse embryonic fibroblasts

DEFF Research Database (Denmark)

Dai, Ning; Christiansen, Jan; Nielsen, Finn

2013-01-01

uncover a new mechanism by which mTOR regulates organismal growth by promoting IGF2 production in the mouse embryo through mTORC2-catalyzed cotranslational IMP1/IMP3 phosphorylation. Inasmuch as TORC2 is activated by association with ribosomes, the present results indicate that mTORC2-catalyzed...... production, and diminished proliferation. The proliferation of the IMP1-null fibroblasts can be restored to wild-type levels by IGF2 in vitro or by re-expression of IMP1, which corrects the defects in IGF2 RNA splicing and translation. The ability of IMP1 to correct these defects is dependent on IMP1...

Treadmill desks: A 1-year prospective trial.

Science.gov (United States)

Koepp, Gabriel A; Manohar, Chinmay U; McCrady-Spitzer, Shelly K; Ben-Ner, Avner; Hamann, Darla J; Runge, Carlisle F; Levine, James A

2013-04-01

Sedentariness is associated with weight gain and obesity. A treadmill desk is the combination of a standing desk and a treadmill that allow employees to work while walking at low speed. The hypothesis was that a 1-year intervention with treadmill desks is associated with an increase in employee daily physical activity (summation of all activity per minute) and a decrease in daily sedentary time (zero activity). Employees (n = 36; 25 women, 11 men) with sedentary jobs (87 ± 27 kg, BMI 29 ± 7 kg/m(2) , n = 10 Lean BMI 30 kg/m(2) ) volunteered to have their traditional desk replaced with a treadmill desk to promote physical activity for 1 year. Daily physical activity (using accelerometers), work performance, body composition, and blood variables were measured at Baseline and 6 and 12 months after the treadmill desk intervention. Subjects who used the treadmill desk increased daily physical activity from baseline 3,353 ± 1,802 activity units (AU)/day to, at 6 months, 4,460 ± 2,376 AU/day (P office workers without affecting work performance. Copyright © 2012 The Obesity Society.

Infrared Spectra of the 10-μm Bands of 1,2-Difluoroethane and 1,1,2-Trifluoroethane: Vibrationally Mediated Torsional Tunneling in 1,1,2-Trifluoroethane

Science.gov (United States)

Stone, Stephen C.; Miller, C. Cameron; Philips, Laura A.; Andrews, A. M.; Fraser, G. T.; Pate, B. H.; Xu, Li-Hong

1995-12-01

The 3-MHz-resolution infrared spectra of the 10-μm bands of thegaucheconformer of 1,2-difluoroethane (HFC152) and theC1-symmetry conformer of 1,1,2-trifluoroethane (HFC143) have been measured using a molecular-beam electric-resonance optothermal spectrometer with a tunable microwave-sideband CO2laser source. For 1,2-difluoroethane, two bands have been studied, the ν17B-symmetry C-F stretch at 1077.3 cm-1and the ν13B-symmetry CH2rock at 896.6 cm-1. Both bands are well fit to a asymmetric-rotor Hamiltonian to better than 0.5 MHz. The ν13band is effectively unperturbed, while the ν17band is weakly perturbed, as shown by the large change in centrifugal distortion constants from the ground state values. Two bands have also been studied for 1,1,2-trifluoroethane, the ν11symmetric CF2stretch at 1077.2 cm-1and the ν13C-C stretch at 905.1 cm-1. One of the two bands, ν11, is unperturbed and fit to near the experimental precision. The ν13vibration, on the other hand, is weakly perturbed by an interaction with a nearby state. This perturbation leads to a doubling or splitting of the lines, due to a perturbation-induced lifting of the degeneracy of the symmetric and antisymmetric tunneling states associated with tunneling between the two equivalentC1forms. For theJ,Kastates studied, the splittings are as large as 37 MHz. Combining this observation with published low-resolution far-infrared measurements of torsional sequence-band and hot-band frequencies and calculations from an empirical torsional potential allows us to identify the perturbing state as ν17+ 6ν18. Here, ν17is the CF2twist and ν18is the torsion. The matrix element responsible for this interaction exchanges eight vibrational quanta!

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

CERN Document Server

Megas, Efstathios

2014-01-01

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

SH2 domain-containing phosphatase 1 regulates pyruvate kinase M2 in hepatocellular carcinoma.

Science.gov (United States)

Tai, Wei-Tien; Hung, Man-Hsin; Chu, Pei-Yi; Chen, Yao-Li; Chen, Li-Ju; Tsai, Ming-Hsien; Chen, Min-Husan; Shiau, Chung-Wai; Boo, Yin-Pin; Chen, Kuen-Feng

2016-04-19

Pyruvate kinase M2 (PKM2) is known to promote tumourigenesis through dimer formation of p-PKM2Y105. Here, we investigated whether SH2-containing protein tyrosine phosphatase 1 (SHP-1) decreases p-PKM2Y105 expression and, thus, determines the sensitivity of sorafenib through inhibiting the nuclear-related function of PKM2. Immunoprecipitation and immunoblot confirmed the effect of SHP-1 on PKM2Y105 dephosphorylation. Lactate production was assayed in cells and tumor samples to determine whether sorafenib reversed the Warburg effect. Clinical hepatocellular carcinoma (HCC) tumor samples were assessed for PKM2 expression. SHP-1 directly dephosphorylated PKM2 at Y105 and further decreased the proliferative activity of PKM2; similar effects were found in sorafenib-treated HCC cells. PKM2 was also found to determine the sensitivity of targeted drugs, such as sorafenib, brivanib, and sunitinib, by SHP-1 activation. Significant sphere-forming activity was found in HCC cells stably expressing PKM2. Clinical findings suggest that PKM2 acts as a predicting factor of early recurrence in patients with HCC, particularly those without known risk factors (63.6%). SHP-1 dephosphorylates PKM2 at Y105 to inhibit nuclear function of PKM2 and determines the efficacy of targeted drugs. Targeting PKM2 by SHP-1 might provide new therapeutic insights for patients with HCC.

How much does PSA matter after 10 years? Outcomes in 10-year clinical NED survivors after definitive radiotherapy for T1-3N0M0 prostate cancer

International Nuclear Information System (INIS)

Johnstone, Peter A. S.; Powell, Curt; Riffenburgh, Robert; Saunders, Eric L.; Bethel, Kelly J.; Huisman, Thomas

1996-01-01

Objective: Institutional policy in the 1970's and 80's dictated that patients with potentially curable prostate cancer undergo PLND prior to definitive XRT. Our group has reported 80% 15-year actuarial cause-specific survival for the 147 patients so treated. Analysis was made of PSA values and clinical outcomes of patients who were clinically without evidence of disease (NED) 10 years after a negative staging pelvic lymphadenectomy and definitive radiation therapy (XRT) for prostate cancer. Materials and Methods: One hundred patients underwent staging pelvic lymphadenectomy between 11/1/74 and 1/1/86, of which 98 had pathologically negative lymph nodes (N 0 ). These patients subsequently underwent definitive radiotherapy; a median dose of 66.6 Gy (range 63-70.2 Gy) was delivered. Forty-two N 0 patients with sufficient follow-up were alive and clinically NED 10 years post-operatively. None of these patients had ever received hormonal therapy. Distribution by disease stage at diagnosis was: Stage A2: 12 pts; Stage B: 19 pts; Stage B2/ C: 6 pts; Stage C: 5 pts. Median follow-up was 12 years 4 months, with a minimum follow-up of 10 years. Results: Of the 42 NED survivors at 10 years, 5 pts died subsequently without PSA data, remaining clinically NED (median 13y 3m post-operatively); 37 patients were alive and without evidence of disease off all therapy at 10 years post-operatively. Most recent PSA data reveal: Bone scans were performed on the 8 patients with elevated PSA. These revealed a single patient with diffuse but asymptomatic bone metastases. Ultrasound-guided sextant biopsies were performed on one 78-year-old patient with elevated PSA 19 years post-operatively, revealing an asymptomatic local recurrence. Conclusions: Radiation therapy delivered to a surgically staged population of prostate cancer patients contributes to normalization of PSA in 78% ((29(37))) of patients with ≥10 year follow-up. Most of these patients will have PSA levels ≤ 1.5 ng/ml. More

Serum HSV-1 and 2 IgM in sexually transmitted diseases - more for screening less for diagnosis: An evaluation of clinical manifestation

Directory of Open Access Journals (Sweden)

Dharmishtha G Tada

2012-01-01

Full Text Available Background: Herpes simplex virus type 2 (HSV-2 is the cause of most genital herpes. Now, HSV-1 has become an important cause and represents even about 30% of genital herpes in some countries. So, study related to genital herpes should consider both HSV-1 and HSV-2. Aim: To examine trends in HSV-1 and 2 seroprevalence by Serum HSV-1 and 2 IgM in all type of sexually transmitted disease (STD patients and also to evaluate correlation of serum HSV-1 and 2 IgM in STD. Materials and Methods: 150 patients attending the STD clinic attached to a tertiary care hospital of Ahmedabad were included in the study. Serum HSV-1 and 2 IgM correlations with clinical manifestations of recurrent and non-recurrent type of genital herpes patients and other non-herpetic STD patients were studied. Results: The overall serum HSV-1 and 2 IgM in STD seroprevalence were 15.66%. Female has significant higher prevalence (P < 0.05. STD cases and HSV seroprevalence were specially concentrated in persons aged 21 to 30 years. Among those positive with HSV, the distribution of STD are wide spread and found in non-herpetic group at high frequency. Out of total 23 serum HSV-1 and 2 IgM positive, 12 and 11 are distributed in herpetic and non-herpetic STDs, respectively. Discussion and Conclusion: Though serum HSV-1 and 2 IgM in STDs are less diagnostic, they help to see the iceberg part of the infection among the population concerned in recent scenario or in another words, it provides recent infective burden.

Phase diagrams of systems of Sr2V2O7-M2V2O7 and of Ba2V2O7-M2V2O7 (M=Ca,Cd)

International Nuclear Information System (INIS)

Fotiev, A.A.; Zhuravlev, V.D.; Zhukov, V.P.

1982-01-01

Using the methods of X-ray phase and differential thermal anlyses phase equilibria in the systems Sr 2 V 2 O 7 -M 2 V 2 O 7 and Ba 2 V 2 O 7 -M 2 V 2 O 7 , where M--Ca, Cd, are studied, their phase diagrams being built. New double pyrovanadates Mosub(0.5)Srsub(1.5)Vsub(2)Osub(7) and MBaV 2 O 7 are found [ru

An ir study of M(1-propanethiol)2Ni(CN)4.G (M=Cd,Ni and G=benzene) clathrates

International Nuclear Information System (INIS)

Kartal, Z.; Tuerkoz, D.; Bahceli, S.

2004-01-01

Two Hofmann-propanethiol-type clathrates of the for M(1-propanethiol) 2 Ni(CN) 4 .G (M=Cd or Ni; G = benzene) have been prepared in the powder form. The 1-propanethiol (1-PT) molecules provide the cavities in which the quest benzene molecules in clathrate structure ar accommodated. The infrared investigations of the obtained clathrates indicate that these compounds are similar in structure to the other Hofmann-type clathrates (Authors)

The distribution of macrophages with a M1 or M2 phenotype in relation to prognosis and the molecular characteristics of colorectal cancer.

Directory of Open Access Journals (Sweden)

Sofia Edin

Full Text Available High macrophage infiltration has been correlated to improved survival in colorectal cancer (CRC. Tumor associated macrophages (TAMs play complex roles in tumorigenesis since they are believed to hold both tumor preventing (M1 macrophages and tumor promoting (M2 macrophages activities. Here we have applied an immunohistochemical approach to determine the degree of infiltrating macrophages with a M1 or M2 phenotype in clinical specimens of CRC in relation to prognosis, both in CRC in general but also in subgroups of CRC defined by microsatellite instability (MSI screening status and the CpG island methylator phenotype (CIMP. A total of 485 consecutive CRC specimens were stained for nitric oxide synthase 2 (NOS2 (also denoted iNOS as a marker for the M1 macrophage phenotype and the scavenger receptor CD163 as a marker for the M2 macrophage phenotype. The average infiltration of NOS2 and CD163 expressing macrophages along the invasive tumor front was semi-quantitatively evaluated using a four-graded scale. Two subtypes of macrophages, displaying M1 (NOS2(+ or M2 (CD163(+ phenotypes, were recognized. We observed a significant correlation between the amount of NOS2(+ and CD163(+ cells (P<0.0001. A strong inverse correlation to tumor stage was found for both NOS2 (P<0.0001 and CD163 (P<0.0001 infiltration. Furthermore, patients harbouring tumors highly infiltrated by NOS2(+ cells had a significantly better prognosis than those infiltrated by few NOS2(+ cells, and this was found to be independent of MSI screening status and CIMP status. No significant difference was found on cancer-specific survival in groups of CRC with different NOS2/CD163 ratios. In conclusion, an increased infiltration of macrophages with a M1 phenotype at the tumor front is accompanied by a concomitant increase in macrophages with a M2 phenotype, and in a stage dependent manner correlated to a better prognosis in patients with CRC.

Some statistical features of the seismic activity related to the recent M8.2 and M7.1 earthquakes in Mexico

Science.gov (United States)

Guzman, L.; Baeza-Blancas, E.; Reyes, I.; Angulo Brown, F.; Rudolf Navarro, A.

2017-12-01

By studying the magnitude earthquake catalogs, previous studies have reported evidence that some changes in the spatial and temporal organization of earthquake activity is observedbefore and after of a main-shock. These previous studies have used different approach methods for detecting clustering behavior and distance-events density in order topoint out the asymmetric behavior of before shocks and aftershocks. Here, we present a statistical analysis of the seismic activity related to the M8.2 and M7.1 earthquakes occurredon Sept. 7th and Sept. 19th, respectively. First, we calculated the interevent time and distance for the period Sept. 7th 2016 until Oct. 20th 2017 for each seismic region ( a radius of 150 km centeredat coordinates of the M8.1 and M7.1). Next, we calculated the "velocity" of the walker as the ratio between the interevent distance and interevent time, and similarly, we also constructed the"acceleration". A slider pointer is considered to estimate some statistical features within time windows of size τ for the velocity and acceleration sequences before and after the main shocks. Specifically, we applied the fractal dimension method to detect changes in the correlation (persistence) behavior of events in the period before the main events.Our preliminary results pointed out that the fractal dimension associated to the velocity and acceleration sequences exhibits changes in the persistence behavior before the mainshock, while thescaling dimension values after the main events resemble a more uncorrelated behavior. Moreover, the relationship between the standard deviation of the velocity and the local mean velocity valuefor a given time window-size τ is described by an exponent close to 1.5, and the cumulative distribution of velocity and acceleration are well described by power law functions after the crash and stretched-exponential-like distribution before the main shock. On the other hand, we present an analysis of patterns of seismicquiescence

Ligand effects on single-electron transfer of isolated iron atoms in the gaseous complexes [(OC)(m)Fe(OH2)(n)](+) (m, n=0-2, m plus n=1, 2)

Czech Academy of Sciences Publication Activity Database

Karlický, F.; Otyepka, M.; Schröder, Detlef

2012-01-01

Roč. 330, 15 Dec (2012), s. 95-99 ISSN 1387-3806 R&D Projects: GA ČR GBP208/12/G016 Grant - others:GA ČR(CZ) GPP208/11/P463; European Regional Development Fund(XE) CZ.1.05/2.1.00/03.0058; GA MŠk(CZ) EE2.3.20.0017 Program:EE Institutional support: RVO:61388963 Keywords : electron transfer * iron carbonyl * microhydration * neutralization-reionization mass * spectrometry * redox transitions Subject RIV: CF - Physical ; Theoretical Chemistry Impact factor: 2.142, year: 2012

Should snacks be recommended in obesity treatment? A 1-year randomized clinical trial.

Science.gov (United States)

Bertéus Forslund, H; Klingström, S; Hagberg, H; Löndahl, M; Torgerson, J S; Lindroos, A K

2008-11-01

To study the effect to recommend no snacks vs three snacks per day on 1-year weight loss. The hypothesis was that it is easier to control energy intake and lose weight if snacks in between meals are omitted. In total 140 patients (36 men, 104 women), aged 18-60 years and body mass index>30 kg/m(2) were randomized and 93 patients (27 men, 66 women) completed the study. A 1-year randomized intervention trial was conducted with two treatment arms with different eating frequencies; 3 meals/day (3M) or 3 meals and 3 snacks/day (3+3M). The patients received regular and individualized counseling by dieticians. Information on eating patterns, dietary intake, weight and metabolic variables was collected at baseline and after 1 year. Over 1 year the 3M group reported a decrease in the number of snacks whereas the 3+3M group reported an increase (-1.1 vs +0.4 snacks/day, respectively, Ptreatment (3M vs 3+3M=-4.1+/-6.1 vs -5.9+/-9.4 kg; P=0.31). Changes in metabolic variables did not differ between the groups, except for high-density lipoprotein that increased in the 3M group but not in 3+3M group (Psnacks or not between meals does not influence 1-year weight loss.

Generation of 1.3 μm and 1.5 μm high-energy Raman radiations in α-BaTeMo2O9 crystals

Science.gov (United States)

Liu, Shande; Zhang, Junjie; Gao, Zeliang; Wei, Lei; Zhang, Shaojun; He, Jingliang; Tao, Xutang

2014-02-01

The generations of high energy 2nd- and 3rd-order stimulated Raman scattering lasers based on the α-BaTeMo2O9 crystal were demonstrated for the first time. The Raman gain coefficient has been compared with that of the YVO4 crystal. A maximum total Stokes radiation energy of 27.3 mJ was obtained, containing 20.1 mJ 2nd-order Stokes energy at 1318 nm, together with 7.2 mJ 3rd-order Stokes energy at 1497 nm, giving an overall conversion efficiency of 35.9% and a slope efficiency of 54.5%. With an optical coating design, a total 3rd- and 4th-order Stokes energy of 16.5 mJ was generated. The maximum energy for 4th-order Stokes radiation at 1731 nm was 2 mJ. The pulse durations for the 2nd-, 3rd-, and 4th-order Stokes shift were 10 ns, 8.6 ns, and 5.2 ns, respectively. Our experimental results show that the α-BTM crystal is a promising Raman crystal for the generations of eye-safe radiations.

Shengui Sansheng San extraction is an angiogenic switch via regulations of AKT/mTOR, ERK1/2 and Notch1 signal pathways after ischemic stroke.

Science.gov (United States)

Liu, Bowen; Luo, Cheng; Zheng, Zhaoguang; Xia, Zhenyan; Zhang, Qian; Ke, Chienchih; Liu, Renshyan; Zhao, Yonghua

2018-05-15

As a traditional Chinese herbal formula, Shengui Sansheng San (SSS) has been employed for stroke treatment more than 300 years. We hypothesize that SSS extraction is an angiogenic switch in penumbra post-stroke, and corresponding mechanisms are investigated. In present study, rats were subjected to permanent middle cerebral artery occlusion model (MCAo) and were treated with low, middle and high doses of SSS extraction. We assessed neurological function and survival rate, and measured infarct volume by 2,3,5-triphenyltetrazolium chloride staining on day 7 after ischemia. von Willebrand factor (vWF), stromal cell-derived factor-1 alpha (SDF-1α) /chemokine (C-X-C motif) receptor 4 (CXCR4) axis, vascular endothelial growth factor (VEGF)/VEGF receptor 2 (VEGFR2) as well as protein kinase B (AKT)/mammalian target of rapamycin (mTOR) /hypoxia-inducible factor-1 alpha (HIF-1α), extracellular signal-regulated kinase 1/2 (ERK1/2) and Notch1 signaling pathways were respectively investigated by immunofluorescence assay or western blotting in vivo and oxygen-glucose-deprived (OGD) brain microvascular endothelial cells (BMECs); simultaneously, wound healing of BMECs and tube formation assay were administrated. Compared to MCAo group, SSS extraction could significantly improve neurological functional scores, survival rate and cerebral infarct volume, enhance vWF + vascular density and perimeter, SDF-1α/CXCR4 axis, VEGF expression, as well as activate AKT/mTOR/HIF-1α and ERK1/2 and inhibit Notch1 pathways in penumbra. In vitro, containing SSS extraction serum increased BMEC migration, capillary formation and VEGF expression via up-regulations of AKT/mTOR and ERK1/2 pathways in OGD BMECs, but ERK inhibitor (U0126) reversed the result of VEGF expression in high dose of SSS group. Additionally, VEGFR2 and Notch1 expressions were suppressed by containing SSS extraction serum. All results were in dose dependent manner. Our study firstly demonstrates that SSS extraction is an

Mild hydrothermal synthesis, crystal structure, spectroscopic and magnetic properties of the [MxIIM2.5-xIII(H2O)2(HPIIIO3)y(PVO4)2-yF] [M=Fe, x=2.08, y=1.58; M=Co, Ni, x=2.5, y=2] compounds

International Nuclear Information System (INIS)

Orive, Joseba; Mesa, Jose L.; Legarra, Estibaliz; Plazaola, Fernando; Arriortua, Maria I.; Rojo, Teofilo

2009-01-01

The [M x II M 2.5-x III (H 2 O) 2 (HP III O 3 ) y (P V O 4 ) 2-y F] [M=Fe (1), x=2.08, y=1.58; M=Co (2), x=2.5, y=2; Ni (3), x=2.5, y=2] compounds have been synthesized using mild hydrothermal conditions at 170 deg. C during five days. Single-crystals of (1) and (2), and polycrystalline sample of (3) were obtained. These isostructural compounds crystallize in the orthorhombic system, space group Aba2, with a=9.9598(2), b=18.8149(4) and c=8.5751(2) A for (1), a=9.9142(7), b=18.570(1) and c=8.4920(5) A for (2) and a=9.8038(2), b=18.2453(2) and c=8.4106(1) A for (3), with Z=8 in the three phases. An X-ray diffraction study reveals that the crystal structure is composed of a three-dimensional skeleton formed by [MO 5 F] and [MO 4 F 2 ] (M=Fe, Co and Ni) octahedra and [HPO 3 ] tetrahedra, partially substituted by [PO 4 ] tetrahedra in phase (1). The IR spectra show the vibrational modes of the water molecules and those of the (HPO 3 ) 2- tetrahedral oxoanions. The thermal study indicates that the limit of thermal stability of these phases is 195 deg. C for (1) and 315 deg. C for (2) and (3). The electronic absorption spectroscopy shows the characteristic bands of the Fe(II), Co(II) and Ni(II) high-spin cations in slightly distorted octahedral geometry. Magnetic measurements indicate the existence of global antiferromagnetic interactions between the metallic centers with a ferromagnetic transition in the three compounds at 28, 14 and 21 K for (1), (2) and (3), respectively. Compound (1) exhibits a hysteresis loop with remnant magnetization and coercive field values of 0.72 emu/mol and 880 Oe, respectively. - Abstract: Polyhedral view of the crystal structure of the [M x II M 2.5-x III (H 2 O) 2 (HP III O 3 ) y (P IV O 4 ) 2-y F] [M=Fe, x=2.08, y=1.58; M=Co, Ni, x=2.5, y=2] compounds showing the sheets along the [001] direction.

Precision hfs of 126Cs(T1/2=1.63 m) by ABMR

International Nuclear Information System (INIS)

Pinard, J.; Duong, H.T.; Marescaux, D.; Stroke, H.H.; Redi, O.; Gustafsson, M.; Nilsson, T.; Matsuki, S.; Kishimoto, Y.; Kominato, K.; Ogawa, I.; Shibata, M.; Tada, M.; Persson, J.R.; Nojiri, Y.; Momota, S.; Inamura, T.T.; Wakasugi, M.; Juncar, P.; Murayama, T.; Nomura, T.; Koizumi, M.

2005-01-01

The hfs separation Δν of 126 Cs(T1/2=1.63 m) in the 6s S1/22 ground state was obtained in a precision measurement near zero magnetic field by means of atomic beam magnetic resonance with laser optical pumping on-line with the CERN-PSB-ISOLDE mass separator. The result, Δν=3629.514 (0.001) MHz, corrects significantly a previous published value from a high-field experiment. With our result, the precision of the nuclear magnetic moment, μ(Cs126)∼0.776μN, is now limited by the influence of extended nuclear structure on the hfs (the Bohr-Weisskopf effect)

Rational Action Selection in 1 1/2- to 3-Year-Olds Following an Extended Training Experience

Science.gov (United States)

Klossek, Ulrike M. H.; Dickinson, Anthony

2012-01-01

Previous studies failed to find evidence for rational action selection in children under 2 years of age. The current study investigated whether younger children required more training to encode the relevant causal relationships. Children between 1 1/2 and 3 years of age were trained over two sessions to perform actions on a touch-sensitive screen…

Radiative rates for E1, E2, M1, and M2 transitions in the Br-like ions Sr IV, Y V, Zr VI, Nb VII, and Mo VIII

International Nuclear Information System (INIS)

Aggarwal, Kanti M.; Keenan, Francis P.

2015-01-01

Energies and lifetimes are reported for the lowest 375 levels of five Br-like ions, namely Sr IV, Y V, Zr VI, Nb VII, and Mo VIII, mostly belonging to the 4s 2 4p 5 , 4s 2 4p 4 4ℓ, 4s4p 6 , 4s 2 4p 4 5ℓ, 4s 2 4p 3 4d 2 , 4s4p 5 4ℓ, and 4s4p 5 5ℓ configurations. Extensive configuration interaction has been included and the general-purpose relativistic atomic structure package (GRASP) has been adopted for the calculations. Additionally, radiative rates are listed among these levels for all E1, E2, M1, and M2 transitions. From a comparison with the measurements, the majority of our energy levels are assessed to be accurate to better than 2%, although discrepancies between theory and experiment for a few are up to 6%. An accuracy assessment of the calculated radiative rates (and lifetimes) is more difficult, because no prior results exist for these ions

Noncanonical Pathway for Regulation of CCL2 Expression by an mTORC1-FOXK1 Axis Promotes Recruitment of Tumor-Associated Macrophages

Directory of Open Access Journals (Sweden)

Hirokazu Nakatsumi

2017-11-01

Full Text Available C-C chemokine ligand 2 (CCL2 plays pivotal roles in tumor formation, progression, and metastasis. Although CCL2 expression has been found to be dependent on the nuclear factor (NF-κB signaling pathway, the regulation of CCL2 production in tumor cells has remained unclear. We have identified a noncanonical pathway for regulation of CCL2 production that is mediated by mammalian target of rapamycin complex 1 (mTORC1 but independent of NF-κB. Multiple phosphoproteomics approaches identified the transcription factor forkhead box K1 (FOXK1 as a downstream target of mTORC1. Activation of mTORC1 induces dephosphorylation of FOXK1, resulting in transactivation of the CCL2 gene. Inhibition of the mTORC1-FOXK1 axis attenuated insulin-induced CCL2 production as well as the accumulation of tumor-associated monocytes-macrophages and tumor progression in mice. Our results suggest that FOXK1 directly links mTORC1 signaling and CCL2 expression in a manner independent of NF-κB and that CCL2 produced by this pathway contributes to tumor progression.

Generation of 2.1 μm wavelength from degenerate high gray track ...

Indian Academy of Sciences (India)

2014-02-12

Feb 12, 2014 ... Home; Journals; Pramana – Journal of Physics; Volume 82; Issue 2. Generation of 2.1 m wavelength from degenerate high gray ... Proceedings of the International Workshop/Conference on Computational Condensed Matter Physics and Materials Science (IWCCMP-2015). Posted on November 27, 2015.

5-Gb/s 0.18-{mu}m CMOS 2:1 multiplexer with integrated clock extraction

Energy Technology Data Exchange (ETDEWEB)

Zhang Changchun; Wang Zhigong; Shi Si; Miao Peng [Institute of RF- and OE-ICs, Southeast University, Nanjing 210096 (China); Tian Ling, E-mail: zgwang@seu.edu.c [School of Science and Engineering, Southeast University, Nanjing 210096 (China)

2009-09-15

A 5-Gb/s 2:1 MUX (multiplexer) with an on-chip integrated clock extraction circuit which possesses the function of automatic phase alignment (APA), has been designed and fabricated in SMIC's 0.18 {mu}m CMOS technology. The chip area is 670 x 780 {mu}m{sup 2}. At a single supply voltage of 1.8 V, the total power consumption is 112 mW with an input sensitivity of less than 50 mV and an output single-ended swing of above 300 mV. The measurement results show that the IC can work reliably at any input data rate between 1.8 and 2.6 Gb/s with no need for external components, reference clock, or phase alignment between data and clock. It can be used in a parallel optic-fiber data interconnecting system.

5-Gb/s 0.18-μm CMOS 2:1 multiplexer with integrated clock extraction

International Nuclear Information System (INIS)

Zhang Changchun; Wang Zhigong; Shi Si; Miao Peng; Tian Ling

2009-01-01

A 5-Gb/s 2:1 MUX (multiplexer) with an on-chip integrated clock extraction circuit which possesses the function of automatic phase alignment (APA), has been designed and fabricated in SMIC's 0.18 μm CMOS technology. The chip area is 670 x 780 μm 2 . At a single supply voltage of 1.8 V, the total power consumption is 112 mW with an input sensitivity of less than 50 mV and an output single-ended swing of above 300 mV. The measurement results show that the IC can work reliably at any input data rate between 1.8 and 2.6 Gb/s with no need for external components, reference clock, or phase alignment between data and clock. It can be used in a parallel optic-fiber data interconnecting system.

5-Gb/s 0.18-μm CMOS 2:1 multiplexer with integrated clock extraction

Science.gov (United States)

Changchun, Zhang; Zhigong, Wang; Si, Shi; Peng, Miao; Ling, Tian

2009-09-01

A 5-Gb/s 2:1 MUX (multiplexer) with an on-chip integrated clock extraction circuit which possesses the function of automatic phase alignment (APA), has been designed and fabricated in SMIC's 0.18 μm CMOS technology. The chip area is 670 × 780 μm2. At a single supply voltage of 1.8 V, the total power consumption is 112 mW with an input sensitivity of less than 50 mV and an output single-ended swing of above 300 mV. The measurement results show that the IC can work reliably at any input data rate between 1.8 and 2.6 Gb/s with no need for external components, reference clock, or phase alignment between data and clock. It can be used in a parallel optic-fiber data interconnecting system.

Effect of insulin analogues on insulin/IGF1 hybrid receptors: increased activation by glargine but not by its metabolites M1 and M2.

Directory of Open Access Journals (Sweden)

Cécile Pierre-Eugene

Full Text Available BACKGROUND: In diabetic patients, the pharmacokinetics of injected human insulin does not permit optimal control of glycemia. Fast and slow acting insulin analogues have been developed, but they may have adverse properties, such as increased mitogenic or anti-apoptotic signaling. Insulin/IGF1 hybrid receptors (IR/IGF1R, present in most tissues, have been proposed to transmit biological effects close to those of IGF1R. However, the study of hybrid receptors is difficult because of the presence of IR and IGF1R homodimers. Our objective was to perform the first study on the pharmacological properties of the five marketed insulin analogues towards IR/IGF1R hybrids. METHODOLOGY: To study the effect of insulin analogues on IR/IGF1R hybrids, we used our previously developed Bioluminescence Resonance Energy Transfer (BRET assay that permits specific analysis of the pharmacological properties of hybrid receptors. Moreover, we have developed a new, highly sensitive BRET-based assay to monitor phophatidylinositol-3 phosphate (PIP(3 production in living cells. Using this assay, we performed a detailed pharmacological analysis of PIP(3 production induced by IGF1, insulin and insulin analogues in living breast cancer-derived MCF-7 and MDA-MB231 cells. RESULTS: Among the five insulin analogues tested, only glargine stimulated IR/IGF1R hybrids with an EC50 that was significantly lower than insulin and close to that of IGF1. Glargine more efficiently stimulated PIP(3 production in MCF-7 cells but not in MDA-MB231 cells as compared to insulin. In contrast, glargine metabolites M1 and M2 showed lower potency for hybrid receptors stimulation, PIP(3 production, Akt and Erk1/2 phosphorylation and DNA synthesis in MCF-7 cells, compared to insulin. CONCLUSION: Glargine, possibly acting through IR/IGF1R hybrids, displays higher potency, whereas its metabolites M1 and M2 display lower potency than insulin for the stimulation of proliferative/anti-apoptotic pathways in

M2-F1 mounted in NASA Ames Research Center 40x80 foot wind tunnel

Science.gov (United States)

1962-01-01

After the first attempted ground-tow tests of the M2-F1 in March 1963, the vehicle was taken to the Ames Research Center, Mountain View, CA, for wind-tunnel testing. During these tests, Milt Thompson and others were in the M2-F1 to position the control surfaces for each test. The wingless, lifting body aircraft design was initially conceived as a means of landing an aircraft horizontally after atmospheric reentry. The absence of wings would make the extreme heat of re-entry less damaging to the vehicle. In 1962, Dryden management approved a program to build a lightweight, unpowered lifting body as a prototype to flight test the wingless concept. It would look like a 'flying bathtub,' and was designated the M2-F1, the 'M' referring to 'manned' and 'F' referring to 'flight' version. It featured a plywood shell placed over a tubular steel frame crafted at Dryden. Construction was completed in 1963. The first flight tests of the M2-F1 were over Rogers Dry Lake at the end of a tow rope attached to a hopped-up Pontiac convertible driven at speeds up to about 120 mph. This vehicle needed to be able to tow the M2-F1 on the Rogers Dry Lakebed adjacent to NASA's Flight Research Center (FRC) at a minimum speed of 100 miles per hour. To do that, it had to handle the 400-pound pull of the M2-F1. Walter 'Whitey' Whiteside, who was a retired Air Force maintenance officer working in the FRC's Flight Operations Division, was a dirt-bike rider and hot-rodder. Together with Boyden 'Bud' Bearce in the Procurement and Supply Branch of the FRC, Whitey acquired a Pontiac Catalina convertible with the largest engine available. He took the car to Bill Straup's renowned hot-rod shop near Long Beach for modification. With a special gearbox and racing slicks, the Pontiac could tow the 1,000-pound M2-F1 110 miles per hour in 30 seconds. It proved adequate for the roughly 400 car tows that got the M2-F1 airborne to prove it could fly safely and to train pilots before they were towed behind a C

1x2M steel performance in the BOR-60 steam generator

International Nuclear Information System (INIS)

Golovanov, V.N.; Shamardin, V.K.; Kondratiev, V.I.; Kryukov, F.N.; Chernobrovkin, Yu.V.; Bulanova, T.M.; Bai, V.F.

The results from studies of 1x2M steel characteristics are presented. This steel was used as the material for the BOR-60 steam generator that had been in operation under the steam generating mode for 18,000 hs (35,000 hs in sodium). It was revealed that the pit corrosion depth on the water/steam side evaporative tube surfaces was about 0.25 μm and less and the total corrosion rate was less than 0.06 mm/y. The mechanical properties of the material were essentially similar both in the evaporator and superheater and met all the requirements imposed on. Based on the analysis of data on the decarbonizaton depth in sodium and on the corrosion damage in water and steam it was concluded that 1x2M steel can be successfully used as the steam generator material at the operating temperatures up to 470 deg. C and had sufficiently longer service-life as compared to 18,000 hs. (author)

Genetics analysis of mutagenic effect on M1 and M2 of arabidopsis thaliana derived from the seeds implanted by low energy ion

International Nuclear Information System (INIS)

Chen Donghua; Liang Qianjin; Zhang Genfa; Zhang Wenjun; Zhang Xiangqi

2001-01-01

Ameliorated RAPD technique was used to analyze the variations and their genetic stability of the gene pool DNAs of M 1 generation of different ion implanted (into seeds) Arabidopsis thaliana and the individual plant DNAs of generations M 1 and M 2 . The analysis of the gene pool DNAs of generation M 1 suggested that: 53 of 178 random primers amplified differential fragments, and multiplication experiments testified that the PCR results of some primers showed considerable stability. The results revealed that variation percentages, within a certain limit, relates to implanting dosage. Particularly, the genetic stability analysis of generation M 2 certificates that: performing PCR analysis by means of the same primers of generation M 1 brought about variation bands identical with that of generation M 1 , so it is possible that variations induced by ion implanting may be truly hereditary

Complete Suppression of the m=2/n=1 NTM Using ECCD on DIII-D

International Nuclear Information System (INIS)

Petty, C.C.; La Haye, R.J.; Luce, T.C.; Humphreys, D.A.; Lohr, J.; Prater, R.; Austin, M.E.; Harvey, R.W.; Wade, M.R.

2003-01-01

Complete suppression of the m=2/n=1 neoclassical tearing mode (NTM) is reported for the first time using electron cyclotron current drive (ECCD) to noninductively generate current at the radius of the island O-point. Experiments on the DIII-D tokamak show that the maximum shrinkage of the m=2/n=1 island amplitude occurs when the ECCD location coincides with the q=2 surface. Estimates of the ECCD radial profile width from the island shrinkage are consistent with ray tracing calculations but may allow for a factor-of-1.5 broadening from electron radial transport

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.

Changes in the T2 value of cartilage after meniscus transplantation over 1 year

International Nuclear Information System (INIS)

Park, Sun-Young; Lee, Sang Hoon; Lee, Min Hee; Chung, Hye Won; Shin, Myung Jin

2017-01-01

To evaluate the changes in the mean T2 values of articular cartilage on serial follow-up images up to 1 year in patients who underwent lateral meniscus allograft transplantation (MAT). Fifty-two patients who underwent lateral MAT surgery at our hospital were evaluated preoperatively and at 2 days, 6 weeks, 3 months, 6 months, and 1 year after MAT using 3.0-T magnetic resonance imaging (MRI) that included T2 mapping. T2 value changes according to the arthroscopic grading of chondromalacia were evaluated in the lateral and medial compartment. Lysholm scores were obtained pre- and postoperatively. The T2 values of cartilage were significantly increased 2 days after operation, and then gradually reduced to the baseline level after 1 year in both compartments. In morphologic assessment performed after 1 year, most areas (92.9 %) showed no interval change of chondromalacia grade. Lyshom knee scores increased significantly from the mean preoperative value of 62.5 (range, 23-95) to 89.7 (range, 64-100) at 1 year (p < 0.001). Mean T2 values of cartilage following MAT exhibited a return to baseline level after 1 year. T2 measurement can be a useful tool for quantitative evaluation of postoperative cartilage changes compared to conventional MRI. (orig.)

Changes in the T2 value of cartilage after meniscus transplantation over 1 year

Energy Technology Data Exchange (ETDEWEB)

Park, Sun-Young [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Songpa-gu, Seoul (Korea, Republic of); Hallym University Sacred Heart Hospital, Department of Radiology, Anyang-si, Gyeonggi-do (Korea, Republic of); Lee, Sang Hoon; Lee, Min Hee; Chung, Hye Won; Shin, Myung Jin [University of Ulsan College of Medicine, Department of Radiology and Research Institute of Radiology, Asan Medical Center, Songpa-gu, Seoul (Korea, Republic of)

2017-04-15

To evaluate the changes in the mean T2 values of articular cartilage on serial follow-up images up to 1 year in patients who underwent lateral meniscus allograft transplantation (MAT). Fifty-two patients who underwent lateral MAT surgery at our hospital were evaluated preoperatively and at 2 days, 6 weeks, 3 months, 6 months, and 1 year after MAT using 3.0-T magnetic resonance imaging (MRI) that included T2 mapping. T2 value changes according to the arthroscopic grading of chondromalacia were evaluated in the lateral and medial compartment. Lysholm scores were obtained pre- and postoperatively. The T2 values of cartilage were significantly increased 2 days after operation, and then gradually reduced to the baseline level after 1 year in both compartments. In morphologic assessment performed after 1 year, most areas (92.9 %) showed no interval change of chondromalacia grade. Lyshom knee scores increased significantly from the mean preoperative value of 62.5 (range, 23-95) to 89.7 (range, 64-100) at 1 year (p < 0.001). Mean T2 values of cartilage following MAT exhibited a return to baseline level after 1 year. T2 measurement can be a useful tool for quantitative evaluation of postoperative cartilage changes compared to conventional MRI. (orig.)

Ho3+/Yb3+ co-doped TeO2-BaF2-Y2O3 glasses for ∼1.2 μm laser applications

Science.gov (United States)

Wang, Shunbin; Li, Chengzhi; Yao, Chuanfei; Jia, Shijie; Jia, Zhixu; Qin, Guanshi; Qin, Weiping

2017-02-01

Intense ∼1.2 μm fluorescence is observed in Ho3+/Yb3+ co-doped TeO2-BaF2-Y2O3 glasses under 915 nm laser diode excitation. The 1.2 μm emission can be ascribed to the transition 5I6→5I8 of Ho3+. With the introducing of BaF2, the content of OH in the glasses drops markedly, and the 1.2 μm emission intensity increases gradually as increasing the concentration percentage of BaF2. Furthermore, microstructured fibers based on the TeO2-BaF2-Y2O3 glasses are fabricated by using a rod-in-tube method, and a relative positive gain of ∼9.42 dB at 1175.3 nm is obtained in a 5 cm long fiber.

Punicalagin, a PTP1B inhibitor, induces M2c phenotype polarization via up-regulation of HO-1 in murine macrophages.

Science.gov (United States)

Xu, Xiaolong; Guo, Yuhong; Zhao, Jingxia; He, Shasha; Wang, Yan; Lin, Yan; Wang, Ning; Liu, Qingquan

2017-09-01

Current data have shown that punicalagin (PUN), an ellagitannin isolated from pomegranate, possesses anti-inflammatory and anti-oxidant properties; however, its direct targets have not yet been reported. This is the first report that PTP1B serves as a direct target of PUN, with IC 50 value of 1.04μM. Results from NPOI further showed that the K on and K off of PUN-PTP1B complex were 3.38e2M -1 s -1 and 4.13e-3s -1 , respectively. The active site Arg24 of PTP1B was identified as a key binding site of PUN by computation simulation and point mutation. Moreover, inhibition of PTP1B by PUN promoted an M2c-like macrophage polarization and enhanced anti-inflammatory cytokines expression, including IL-10 and M-CSF. Based on gene expression profile, we elucidated that PUN treatment significantly up-regulated 275 genes and down-regulated 1059 genes. M1-like macrophage marker genes, such as Tlr4, Irf1/2, Hmgb1, and Stat1 were down-regulated, while M2 marker genes, including Tmem171, Gpr35, Csf1, Il1rn, Cebpb, Fos, Vegfα, Slc11a1, and Bhlhe40 were up-regulated in PUN-treated macrophages. Hmox-1, a gene encoding HO-1 protein, was preferentially expressed with 16-fold change. Inhibition of HO-1 obviously restored PUN-induced M2 polarization and IL-10 secretion. In addition, phosphorylation of both Akt and STAT3 contributed to PUN-induced HO-1 expression. This study provided new insights into the mechanisms of PUN-mediated anti-inflammatory and anti-oxidant activities and provided new therapeutic strategies for inflammatory diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Effects of clopidogrel and clarithromycin on the disposition of sibutramine and its active metabolites M1 and M2 in relation to CYP2B6*6 polymorphism.

Science.gov (United States)

Pan, Wei; Bae, Soo-Kyung; Shim, Eon-Jeong; Park, Sung-Eun; Lee, Sang-Seop; Park, Soo-Jin; Yeo, Chang-Woo; Zhou, Hong-Hao; Shon, Ji-Hong; Shin, Jae-Gook

2013-02-01

Plasma concentrations of sibutramine and its two active metabolites after single oral dose of sibutramine were determined in Korean healthy male subjects with different CYP2B6 genotypes (CYP2B6*1/*1, *1/*6 and *6/*6), either alone or after four-day pretreatment with clopidogrel or clarithromycin. The pretreatment with clopidogrel and clarithromycin raised the mean area under the concentration-time curve (AUC) of sibutramine by 163% and 255%, respectively. Co-administration of clarithromycin, combined with CYP2B6*6/*6 genotype, led to highest concentration of sibutramine. The molar sum AUC (M1 + M2) was raised by 35% in the clopidogrel phase but not significantly affected by clarithromycin or CYP2B6 genotype. The CYP2B6*6/*6 subjects in the clopidogrel phase showed the highest molar AUC (M1 + M2) among three genotype groups throughout the three phases. The exposure of sibutramine and its metabolites seemed to be associated with the CYP2B6 genotype. The treatment of clopidogrel significantly altered the disposition of active metabolites as well as sibutramine, but clarithromycin only affects the disposition of sibutramine. These results suggest that the perturbation of CYP2B6 activity may contribute to the inter-individual variation of sibutramine drug responses although the clinical relevance is remained to be established.

Functionalized cobalt bis(dicarbollide) ions as selective extraction reagents for removal of M2+ and M3+ cations from nuclear waste, crystal and molecular structures of the [8,8 '-mu-CIP(O)(O)(2)(1,2-C2B9H10)(2)-3,3 '-Co]HN(C2H5)(3) and [8,8 '-mu-Et2NP(O)(O)(2) (1,2-C2B9H10)(2)-3,3 '-Co](HN(CH3)(3))

Czech Academy of Sciences Publication Activity Database

Plešek, Jaromír; Grüner, Bohumír; Císařová, I.; Báča, Jiří; Selucký, P.; Rais, J.

2002-01-01

Roč. 657, 1-2 (2002), s. 59-70 ISSN 0022-328X R&D Projects: GA ČR GA104/99/1096; GA ČR GA104/01/0142; GA ČR GA203/99/M037; GA MŠk LN00A028 Institutional research plan: CEZ:AV0Z4032918 Keywords : carboranes * metallaboranes * liquid-liquid extraction Subject RIV: CA - Inorganic Chemistry Impact factor: 1.901, year: 2002

Form factors of descendant operators: reduction to perturbed M(2,2s+1) models

International Nuclear Information System (INIS)

Lashkevich, Michael; Pugai, Yaroslav

2015-01-01

In the framework of the algebraic approach to form factors in two-dimensional integrable models of quantum field theory we consider the reduction of the sine-Gordon model to the Φ 13 -perturbation of minimal conformal models of the M(2,2s+1) series. We find in an algebraic form the condition of compatibility of local operators with the reduction. We propose a construction that make it possible to obtain reduction compatible local operators in terms of screening currents. As an application we obtain exact multiparticle form factors for the compatible with the reduction conserved currents T ±2k , Θ ±(2k−2) , which correspond to the spin ±(2k−1) integrals of motion, for any positive integer k. Furthermore, we obtain all form factors of the operators T 2k T −2l , which generalize the famous TT̄ operator. The construction is analytic in the s parameter and, therefore, makes sense in the sine-Gordon theory.

Promiscuity of MCMV immunoevasin of NKG2D: m138/fcr-1 down-modulates RAE-1epsilon in addition to MULT-1 and H60.

Science.gov (United States)

Arapović, Jurica; Lenac Rovis, Tihana; Reddy, Anil Butchi; Krmpotić, Astrid; Jonjić, Stipan

2009-11-01

Both human and mouse cytomegalovirus (CMV) encode proteins that inhibit the activation of NK cells by down-regulating the cellular ligands for activating NK cell receptor, NKG2D. MCMV proteins m145, m152 and m155 interfere with the expression of all known NKG2D ligands, MULT-1, RAE-1 family members and H60, respectively, whereas m138 affects the expression of MULT-1 and H60. Here we show that m152 affects the maturation of newly synthesized RAE-1 molecules, but is not sufficient to prevent surface expression of RAE-1varepsilon. We have identified m138 as a main inhibitor of the surface expression of RAE-1varepsilon. In contrast to m152, m138 affects the surface-resident protein leading to its endocytosis, which can be prevented by a dynamin inhibitor. Moreover, we demonstrated that m138 does not need other viral proteins to down-modulate the expression of RAE-1varepsilon.

AZD2014 Radiosensitizes Oral Squamous Cell Carcinoma by Inhibiting AKT/mTOR Axis and Inducing G1/G2/M Cell Cycle Arrest.

Directory of Open Access Journals (Sweden)

Chih-Chia Yu

Full Text Available Oral squamous cell carcinoma (OSCC is one of the most common malignant neoplasms in Taiwan. Activation of the mTOR signaling pathway has been linked to decreased radiation responsiveness in human oral cancer, thus it limits efficacy of radiotherapy. To address this question, we investigated the effect of AZD2014, a novel small molecular ATP-competitive inhibitor of mTORC1 and mTORC2 kinase, as a radiosensitizer in primary OSCC and OSCC-derived cell line models.We isolated primary tumor cells from OSCC tissues and cell lines. AZD2014 was administered with and without ionizing radiation. The radiosensitizing effect of AZD2014 were then assessed using cell viability assays, clonogenic survival assays, and cell cycle analyses. Western blotting was used to detect protein expression.Combination treatment with AZD2014 and irradiation resulted in significant reduction in OSCC cell line and primary OSCC cell colony formation due to the enhanced inhibition of AKT and both mTORC1 and mTORC2 activity. Pre-treatment with AZD2014 in irradiated oral cancer cells induced tumor cell cycle arrest at the G1 and G2/M phases, which led to disruption of cyclin D1-CDK4 and cyclin B1-CDC2 complexes. Moreover, AZD2014 synergized with radiation to promote both apoptosis and autophagy by increasing caspase-3 and LC3 in primary OSCC cells.These findings suggest that in irradiated OSCC cells, co-treatment with AZD2014, which targets mTORC1 and mTORC2 blockade, is an effective radiosensitizing strategy for oral squamous cell carcinoma.

Conditional cancer-specific mortality in T4, N1, or M1 prostate cancer: implications for long-term prognosis

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Muralidhar, Vinayak; Mahal, Brandon A.; Nguyen, Paul L.

2015-01-01

The risk of prostate cancer-specific mortality (PCSM) following a diagnosis of prostate cancer may improve after patients have survived a number of years after diagnosis. We sought to determine long-term conditional PCSM for patients with stage T4, N1, or M1 prostate cancer. We identified 66,817 patients diagnosed with stage IV (T4N0M0, N1M0, or M1) prostate cancer between 1973 and 2011 using the Surveillance, Epidemiology, and End Results (SEER) database. Conditional five-year PCSM was evaluated for each group of patients at 5, 10, and 15 years of survival according to the Fine & Gray model for competing risks after adjusting for tumor grade, age, income level, and marital status. Race-stratified analyses were also performed. There were 13,345 patients with T4 disease, 12,450 patients with N1 disease, and 41,022 patients with M1 disease. Median follow-up among survivors in the three groups was 123 months (range: 0–382 months), 61 months (range: 0–410 months), and 30 months (range: 0–370 months), respectively. Conditional PCSM improved in all three groups over time. Among patients with T4 disease, 5-year PCSM improved from 13.9 % at diagnosis to 11.2, 8.1, and 6.5 % conditioned on 5, 10, or 15 years of survival, respectively (p < 0.001 in all cases). In patients with N1 disease, 5-year PCSM increased within the first five years and decreased thereafter, from 18.9 % at diagnosis to 21.4 % (p < 0.001), 17.6 % (p = 0.055), and 13.8 % (p < 0.001), respectively. In patients with metastatic disease, 5-year PCSM improved from 57.2 % at diagnosis to 41.1, 28.8, and 20.8 %, respectively (p < 0.001). White race was associated with a greater increase in conditional survival compared to non-white race among those with T4 or N1 disease. While patients with T4, N1, or M1 prostate cancer are never “cured,” their odds of cancer-specific survival increase substantially after they have survived for 5 or more years. Physicians who take care of patients with prostate cancer

Mammary Stem Cell Self-Renewal Is Regulated by Slit2/Robo1 Signaling through SNAI1 and mINSC

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Mimmi S. Ballard

2015-10-01

Full Text Available Tissue homeostasis requires somatic stem cell maintenance; however, mechanisms regulating this process during organogenesis are not well understood. Here, we identify asymmetrically renewing basal and luminal stem cells in the mammary end bud. We demonstrate that SLIT2/ROBO1 signaling regulates the choice between self-renewing asymmetric cell divisions (ACDs and expansive symmetric cell divisions (SCDs by governing Inscuteable (mInsc, a key member of the spindle orientation machinery, through the transcription factor Snail (SNAI1. Loss of SLIT2/ROBO1 signaling increases SNAI1 in the nucleus. Overexpression of SNAI1 increases mInsc expression, an effect that is inhibited by SLIT2 treatment. Increased mInsc does not change cell proliferation in the mammary gland (MG but instead causes more basal cap cells to divide via SCD, at the expense of ACD, leading to more stem cells and larger outgrowths. Together, our studies provide insight into how the number of mammary stem cells is regulated by the extracellular cue SLIT2.

Prostaglandin E2 activates the mTORC1 pathway through an EP4/cAMP/PKA- and EP1/Ca2+-mediated mechanism in the human pancreatic carcinoma cell line PANC-1.

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Chang, Hui-Hua; Young, Steven H; Sinnett-Smith, James; Chou, Caroline Ei Ne; Moro, Aune; Hertzer, Kathleen M; Hines, Oscar Joe; Rozengurt, Enrique; Eibl, Guido

2015-11-15

Obesity, a known risk factor for pancreatic cancer, is associated with inflammation and insulin resistance. Proinflammatory prostaglandin E2 (PGE2) and elevated insulin-like growth factor type 1 (IGF-1), related to insulin resistance, are shown to play critical roles in pancreatic cancer progression. We aimed to explore a potential cross talk between PGE2 signaling and the IGF-1/Akt/mammalian target of rapamycin complex 1 (mTORC1) pathway in pancreatic cancer, which may be a key to unraveling the obesity-cancer link. In PANC-1 human pancreatic cancer cells, we showed that PGE2 stimulated mTORC1 activity independently of Akt, as evaluated by downstream signaling events. Subsequently, using pharmacological and genetic approaches, we demonstrated that PGE2-induced mTORC1 activation is mediated by the EP4/cAMP/PKA pathway, as well as an EP1/Ca(2+)-dependent pathway. The cooperative roles of the two pathways were supported by the maximal inhibition achieved with the combined pharmacological blockade, and the coexistence of highly expressed EP1 (mediating the Ca(2+) response) and EP2 or EP4 (mediating the cAMP/PKA pathway) in PANC-1 cells and in the prostate cancer line PC-3, which also robustly exhibited PGE2-induced mTORC1 activation, as identified from a screen in various cancer cell lines. Importantly, we showed a reinforcing interaction between PGE2 and IGF-1 on mTORC1 signaling, with an increase in IL-23 production as a cellular outcome. Our data reveal a previously unrecognized mechanism of PGE2-stimulated mTORC1 activation mediated by EP4/cAMP/PKA and EP1/Ca(2+) signaling, which may be of great importance in elucidating the promoting effects of obesity in pancreatic cancer. Ultimately, a precise understanding of these molecular links may provide novel targets for efficacious interventions devoid of adverse effects. Copyright © 2015 the American Physiological Society.

LAPTM4b recruits the LAT1-4F2hc Leu transporter to lysosomes and promotes mTORC1 activation.

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Milkereit, Ruth; Persaud, Avinash; Vanoaica, Liviu; Guetg, Adriano; Verrey, Francois; Rotin, Daniela

2015-05-22

Mammalian target of rapamycin 1 (mTORC1), a master regulator of cellular growth, is activated downstream of growth factors, energy signalling and intracellular essential amino acids (EAAs) such as Leu. mTORC1 activation occurs at the lysosomal membrane, and involves V-ATPase stimulation by intra-lysosomal EAA (inside-out activation), leading to activation of the Ragulator, RagA/B-GTP and mTORC1 via Rheb-GTP. How Leu enters the lysosomes is unknown. Here we identified the lysosomal protein LAPTM4b as a binding partner for the Leu transporter, LAT1-4F2hc (SLC7A5-SLAC3A2). We show that LAPTM4b recruits LAT1-4F2hc to lysosomes, leading to uptake of Leu into lysosomes, and is required for mTORC1 activation via V-ATPase following EAA or Leu stimulation. These results demonstrate a functional Leu transporter at the lysosome, and help explain the inside-out lysosomal activation of mTORC1 by Leu/EAA.

Progesterone therapy induces an M1 to M2 switch in microglia phenotype and suppresses NLRP3 inflammasome in a cuprizone-induced demyelination mouse model.

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Aryanpour, Roya; Pasbakhsh, Parichehr; Zibara, Kazem; Namjoo, Zeinab; Beigi Boroujeni, Fatemeh; Shahbeigi, Saeed; Kashani, Iraj Ragerdi; Beyer, Cordian; Zendehdel, Adib

2017-10-01

Demyelination of the central nervous system (CNS) has been associated to reactive microglia in neurodegenerative disorders, such as multiple sclerosis (MS). The M1 microglia phenotype plays a pro-inflammatory role while M2 is involved in anti-inflammatory processes in the brain. In this study, CPZ-induced demyelination mouse model was used to investigate the effect of progesterone (PRO) therapy on microglia activation and neuro-inflammation. Results showed that progesterone therapy (CPZ+PRO) decreased neurological behavioral deficits, as demonstrated by significantly decreased escape latencies, in comparison to CPZ mice. In addition, CPZ+PRO caused a significant reduction in the mRNA expression levels of M1-markers (iNOS, CD86, MHC-II and TNF-α) in the corpus callosum region, whereas the expression of M2-markers (Trem-2, CD206, Arg-1 and TGF-β) was significantly increased, in comparison to CPZ mice. Moreover, CPZ+PRO resulted in a significant decrease in the number of iNOS + and Iba-1 + /iNOS + cells (M1), whereas TREM-2 + and Iba-1 + /TREM-2 + cells (M2) significantly increased, in comparison to CPZ group. Furthermore, CPZ+PRO caused a significant decrease in mRNA and protein expression levels of NLRP3 and IL-18 (~2-fold), in comparison to the CPZ group. Finally, CPZ+PRO therapy was accompanied with reduced levels of demyelination, compared to CPZ, as confirmed by immunofluorescence to myelin basic protein (MBP) and Luxol Fast Blue (LFB) staining, as well as transmission electron microscopy (TEM) analysis. In summary, we reported for the first time that PRO therapy causes polarization of M2 microglia, attenuation of M1 phenotype, and suppression of NLRP3 inflammasome in a CPZ-induced demyelination model of MS. Copyright © 2017 Elsevier B.V. All rights reserved.

Preparation and assessment of [{sup 99m}Tc]technetium aquacarbonyl complexes with 1,2-diaminoethane-N-substituted ligands for tumor detection; Preparo e avaliacao de complexos de [{sup 99m}Tc]tecnecio aquacarbonil com ligantes 1,2-diaminoetano-N-substituidos para deteccao de tumores

Energy Technology Data Exchange (ETDEWEB)

Radin, Adriano

2010-07-01

Over least 15 years the complex [[{sup 99m}Tc](H{sub 2}0){sub 3}(CO){sub 3}]{sup +} has been used as an intermediary to obtain technetium radiopharmaceuticals for applications in cardiology, neurology and oncology. Two important characteristics of this molecule are: the facility for obtaining that compound from aqueous solutions and the easiness of substituting H{sub 2}O molecules by atoms of other ligand molecules. In this project we prepared new complexes [[{sup 99m}Tc](CMN{sup S001-3})(H{sub 2}O)(CO){sub 3}]{sup +}, where (CMNS001) = N-[(4-methoxy) benzyl]-1,2-diaminoethane, (CMNS003) = N,N'-bis-[(4-methoxy)benzyl]-1,2-diaminoethane, and assessed the uptake of these complexes in murine melanoma cancer cell B16F10 and breast cells MCF-7 and MDA-MD-231, and compared with [[{sup 99m}](MIBI){sub 6}]{sup +} uptake. In vitro uptake for both new technetium complex reached values close to 5%, for all cell lines, whereas the [[{sup 99m}Tc](MIBI){sub 6}]{sup +} uptake was close to 1 %. The assessment of subcellular distribution showed high accumulation of the new complex in the membrane fraction, for MDAMB-231, while for B16F10 accumulation occurred both in membrane and cytoplasm; the concentration of [[{sup 99m}Tc](MIBI){sub 6}]{sup +} was mainly in the cytoplasm portion. Biodistribution study in mice allowed to observe the capture of up to 1.6% of the administered dose per gram of tumor tissue for the complex [[{sup 99m}Tc](CMNS001)(H{sub 2}O)(CO){sub 3}]{sup +}, whereas other organs such as heart, lung and muscle, showed uptake of about 5.6%, 6.4% and 2%, respectively. The complexes in this work showed a high rate of uptake in vitro, but was not reproduced in vivo model, which can be related to low concentration of the complexes inside the cells and reduced vascularity of tumor tissue, with lower intake of complex through the blood system. (author)

Dry deposition of gaseous oxidized mercury in Western Maryland.

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Castro, Mark S; Moore, Chris; Sherwell, John; Brooks, Steve B

2012-02-15

The purpose of this study was to directly measure the dry deposition of gaseous oxidized mercury (GOM) in western Maryland. Annual estimates were made using passive ion-exchange surrogate surfaces and a resistance model. Surrogate surfaces were deployed for seventeen weekly sampling periods between September 2009 and October 2010. Dry deposition rates from surrogate surfaces ranged from 80 to 1512 pgm(-2)h(-1). GOM dry deposition rates were strongly correlated (r(2)=0.75) with the weekly average atmospheric GOM concentrations, which ranged from 2.3 to 34.1 pgm(-3). Dry deposition of GOM could be predicted from the ambient air concentrations of GOM using this equation: GOM dry deposition (pgm(-2)h(-1))=43.2 × GOM concentration-80.3. Dry deposition velocities computed using GOM concentrations and surrogate surface GOM dry deposition rates, ranged from 0.2 to 1.7 cms(-1). Modeled dry deposition rates were highly correlated (r(2)=0.80) with surrogate surface dry deposition rates. Using the overall weekly average surrogate surface dry deposition rate (369 ± 340 pg m(-2)h(-1)), we estimated an annual GOM dry deposition rate of 3.2 μg m(-2)year(-1). Using the resistance model, we estimated an annual GOM dry deposition rate of 3.5 μg m(-2)year(-1). Our annual GOM dry deposition rates were similar to the dry deposition (3.3 μg m(-2)h(-1)) of gaseous elemental mercury (GEM) at our site. In addition, annual GOM dry deposition was approximately 1/2 of the average annual wet deposition of total mercury (7.7 ± 1.9 μg m(-2)year(-1)) at our site. Total annual mercury deposition from dry deposition of GOM and GEM and wet deposition was approximately 14.4 μg m(-2)year(-1), which was similar to the average annual litterfall deposition (15 ± 2.1 μg m(-2)year(-1)) of mercury, which was also measured at our site. Copyright © 2012 Elsevier B.V. All rights reserved.

Probing the electronic properties of ternary AnM3n−1B2n (n = 1: A = Ca, Sr; M = Rh, Ir and n = 3: A = Ca, Sr; M = Rh phases: observation of superconductivity

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Hiroyuki Takeya, Mohammed ElMassalami, Luis A Terrazos, Raul E Rapp, Rodrigo B Capaz, Hiroki Fujii, Yoshihiko Takano, Mathias Doerr and Sergey A Granovsky

2013-01-01

Full Text Available We follow the evolution of the electronic properties of the titled homologous series when n as well as the atomic type of A and M are varied where for n = 1, A = Ca, Sr and M = Rh, Ir while for n = 3, A = Ca, Sr and M = Rh. The crystal structure of n = 1 members is known to be CaRh2B2-type (Fddd, while that of n = 3 is Ca3Rh8B6-type (Fmmm; the latter can be visualized as a stacking of structural fragments from AM3B2 (P6/mmm and AM2B2. The metallic properties of the n = 1 and 3 members are distinctly different: on the one hand, the n = 1 members are characterized by a linear coefficient of the electronic specific heat γ ≈ 3 mJ mol−1 K−2, a Debye temperature θD ≈ 300 K, a normal conductivity down to 2 K and a relatively strong linear magnetoresistivity for fields up to 150 kOe. The n = 3 family, on the other hand, exhibits γ ≈ 18 mJ mol−1 K−2, θD ≈ 330 K, a weak linear magnetoresistivity and an onset of superconductivity (for Ca3Rh8B6, Tc = 4.0 K and Hc2 = 14.5 kOe, while for Sr3Rh8 B6, Tc = 3.4 K and Hc2 ≈ 4.0 kOe. These remarkable differences are consistent with the findings of the electronic band structures and density of state (DOS calculations. In particular, satisfactory agreement between the measured and calculated γ was obtained. Furthermore, the Fermi level, EF, of Ca3Rh8B6 lies at almost the top of a pronounced local DOS peak, while that of CaRh2B2 lies at a local valley: this is the main reason behind the differences between the, e.g., superconducting properties. Finally, although all atoms contribute to the DOS at EF, the contribution of the Rh atoms is the strongest.

Probing the electronic properties of ternary AnM3n−1B2n (n = 1: A = Ca, Sr; M = Rh, Ir and n = 3: A = Ca, Sr; M = Rh) phases: observation of superconductivity

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Takeya, Hiroyuki; ElMassalami, Mohammed; Terrazos, Luis A; Rapp, Raul E; Capaz, Rodrigo B; Fujii, Hiroki; Takano, Yoshihiko; Doerr, Mathias; Granovsky, Sergey A

2013-01-01

We follow the evolution of the electronic properties of the titled homologous series when n as well as the atomic type of A and M are varied where for n = 1, A = Ca, Sr and M = Rh, Ir while for n = 3, A = Ca, Sr and M = Rh. The crystal structure of n = 1 members is known to be CaRh2B2-type (Fddd), while that of n = 3 is Ca3Rh8B6-type (Fmmm); the latter can be visualized as a stacking of structural fragments from AM3B2 (P6/mmm) and AM2B2. The metallic properties of the n = 1 and 3 members are distinctly different: on the one hand, the n = 1 members are characterized by a linear coefficient of the electronic specific heat γ ≈ 3 mJ mol−1 K−2, a Debye temperature θD ≈ 300 K, a normal conductivity down to 2 K and a relatively strong linear magnetoresistivity for fields up to 150 kOe. The n = 3 family, on the other hand, exhibits γ ≈ 18 mJ mol−1 K−2, θD ≈ 330 K, a weak linear magnetoresistivity and an onset of superconductivity (for Ca3Rh8B6, Tc = 4.0 K and Hc2 = 14.5 kOe, while for Sr3Rh8 B6, Tc = 3.4 K and Hc2 ≈ 4.0 kOe). These remarkable differences are consistent with the findings of the electronic band structures and density of state (DOS) calculations. In particular, satisfactory agreement between the measured and calculated γ was obtained. Furthermore, the Fermi level, EF, of Ca3Rh8B6 lies at almost the top of a pronounced local DOS peak, while that of CaRh2B2 lies at a local valley: this is the main reason behind the differences between the, e.g., superconducting properties. Finally, although all atoms contribute to the DOS at EF, the contribution of the Rh atoms is the strongest. PMID:27877576

Anticonvulsant activity of a mGlu(4alpha) receptor selective agonist, (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid.

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Chapman, A G; Talebi, A; Yip, P K; Meldrum, B S

2001-07-20

The metabotropic Group III agonist, (1S,3R,4S)-1-aminocyclopentane-1,2,4-tricarboxylic acid (ACPT-1), selective for the mGlu(4alpha) receptor, suppresses sound-induced seizures in DBA/2 mice following its intracerebroventricular (i.c.v.) administration (ED(50) 5.6 [2.9-10.7], nmol i.c.v., 15 min, clonic phase) and in genetically epilepsy-prone (GEP) rats following focal administration into the inferior colliculus (ED(50) 0.08 [0.01-0.50], nmol, 60 min, clonic phase). ACPT-1 also protects against clonic seizures induced in DBA/2 mice by the Group I agonist, (RS)-3,5-dihydroxyphenylglycine (3,5-DHPG) (ED(50) 0.60 [0.29-1.2], nmol i.c.v.) and by the Group III antagonist, (RS)-alpha-methylserine-O-phosphate (MSOP) (ED(50) 49.3 [37.9-64.1], nmol i.c.v.). Another Group III agonist, (RS)-4-phosphonophenyl-glycine (PPG), preferentially activating the mGlu(8) receptor, previously shown to protect against sound-induced seizures in DBA/2 mice and GEP rats, also protects against seizures induced in DBA/2 by 3,5-DHPG (ED(50) 3.7 [2.4-5.7], nmol i.c.v.) and by the Group III antagonist, MSOP (ED(50) 40.2 [21.0-77.0], nmol i.c.v.). At very high doses (500 nmol i.c.v. and above), Group III antagonists have pro-convulsant and convulsant activity. The anticonvulsant protection against sound-induced seizures in DBA/2 mice provided by a fully protective dose (20 nmol, i.c.v.) of the mGlu(4) receptor agonist ACPT-1, is partially reversed by the co-administration of the Group III antagonists, MSOP, (RS)-alpha-methyl-4-phosphonophenylglycine (MPPG) or (S)-2-amino-2-methyl-4-phosphonobutanoic acid (MAP4), in the 20-50 nmol dose range. At doses of 50-200 nmol, MPPG and MAP4 cause further reversal of the ACPT-1 anticonvulsant protection, while the MSOP effect on ACPT-1 protection is abolished at higher doses. In contrast, the anticonvulsant protection against sound-induced seizures in DBA/2 mice provided by a fully protective dose (20 nmol, i.c.v.) of the mGlu(8) receptor agonist PPG, is not

Pulsed laser deposition of {CeO_2} and {Ce_{1-x}M_xO_2} (M = La, Zr): Application to insulating barrier in cuprate heterostructures

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Berger, S.; Contour, J.-P.; Drouet, M.; Durand, O.; Khodan, A.; Michel, D.; Régi, F.-X.

1998-03-01

SrTiO_3 had been often tentatively used as an insulating barrier for HT superconductor/insulator heterostructures. Unfortunately, the deposition of SrTiO_3 on the YBa_2Cu_3O_7 inverse interface results in a poor epitaxial regrowth producing a high roughness dislocated titanate layer. Taking into account the good matching with YBa_2Cu_3O_7 and LaAlO_3, CeO_2 and Ce_{1-x}M_xO_2 (M = La, Zr), epitaxial layers were grown by pulsed laser deposition on LaAlO_3 substrates and introduced into YBa_2Cu_3O_7 based heterostructures as insulating barrier. After adjusting the growth parameters from RHEED oscillations, epitaxial growth is achieved, the oxide crystal axes being rotated by 45^circ from those of the substrate. The surface roughness of 250 nm thick films is very low with a rms value lower than 0.5 nm over 1;μ m^2. The YBa_2Cu_3O_7 layers of a YBa_2Cu_3O_7/CeO_2 /YBa_2Cu_3O_7 heterostructures grown using these optimized parameters show an independent resistive transition, when the thickness is larger than 25 nm, respectively at T_c_1 = 89.6;K and T_c_2 = 91.4;{K}. SrTiO3 est souvent utilisé comme barrière isolante dans des hétérostructures SIS de cuprates supraconducteurs, cependant les défauts générés lors de la croissance de ce titanate sur l'interface inverse de YBa2Cu3O7 conduisent à un matériau dont la qualité cristalline et les propriétés physiques sont médiocres. L'oxyde de cérium CeO2 est également une barrière isolante potentielle intéressante pour ces structures SIS basées sur YBa2Cu3O7 car cet oxyde cubique (a = 0,5411 nm, asqrt{2}/2 = 0,3825 nm) qui est peu désaccordé par rapport au plan ab du cuprate (Δ a/a = - 0,18 %, Δ b/a = 1,6 %) présente de plus un coefficient de dilatation thermique (10,6 × 10^{-6 circ}C^{-1}) très voisin de celui de YBa2Cu3O7 (13 × 10^{-6 circ}C^{-1}). Nous avons donc étudié l'épitaxie de CeO2 et des oxydes de type Ce{1-x}MxO2 (M = La, Zr) en ablation laser pulsée afin de définir des conditions de

Replication-independent chromatin loading of Dnmt1 during G2 and M phases

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Easwaran, Hariharan P; Schermelleh, Lothar; Leonhardt, Heinrich; Cardoso, M Cristina

2004-01-01

The major DNA methyltransferase, Dnmt1, associates with DNA replication sites in S phase maintaining the methylation pattern in the newly synthesized strand. In view of the slow kinetics of Dnmt1 in vitro versus the fast progression of the replication fork, we have tested whether Dnmt1 associates with chromatin beyond S phase. Using time-lapse microscopy of mammalian cells expressing green-fluorescent-protein-tagged Dnmt1 and DsRed-tagged DNA Ligase I as a cell cycle progression marker, we have found that Dnmt1 associates with chromatin during G2 and M. This association is mediated by a specific targeting sequence, shows strong preference for constitutive but not facultative heterochromatin and is independent of heterochromatin-specific histone H3 Lys 9 trimethylation, SUV39H and HP1. Moreover, photobleaching analyses showed that Dnmt1 is continuously loaded onto chromatin throughout G2 and M, indicating a replication-independent role of Dnmt1 that could represent a novel and separate pathway to maintain DNA methylation. PMID:15550930

Preparation and assessment of [99mTc]technetium aquacarbonyl complexes with 1,2-diaminoethane-N-substituted ligands for tumor detection

International Nuclear Information System (INIS)

Radin, Adriano

2010-01-01

Over least 15 years the complex [[ 99m Tc](H 2 0) 3 (CO) 3 ] + has been used as an intermediary to obtain technetium radiopharmaceuticals for applications in cardiology, neurology and oncology. Two important characteristics of this molecule are: the facility for obtaining that compound from aqueous solutions and the easiness of substituting H 2 O molecules by atoms of other ligand molecules. In this project we prepared new complexes [[ 99m Tc](CMN S001-3 )(H 2 O)(CO) 3 ] + , where (CMNS001) = N-[(4-methoxy) benzyl]-1,2-diaminoethane, (CMNS003) = N,N'-bis-[(4-methoxy)benzyl]-1,2-diaminoethane, and assessed the uptake of these complexes in murine melanoma cancer cell B16F10 and breast cells MCF-7 and MDA-MD-231, and compared with [[ 99m ](MIBI) 6 ] + uptake. In vitro uptake for both new technetium complex reached values close to 5%, for all cell lines, whereas the [[ 99m Tc](MIBI) 6 ] + uptake was close to 1 %. The assessment of subcellular distribution showed high accumulation of the new complex in the membrane fraction, for MDAMB-231, while for B16F10 accumulation occurred both in membrane and cytoplasm; the concentration of [[ 99m Tc](MIBI) 6 ] + was mainly in the cytoplasm portion. Biodistribution study in mice allowed to observe the capture of up to 1.6% of the administered dose per gram of tumor tissue for the complex [[ 99m Tc](CMNS001)(H 2 O)(CO) 3 ] + , whereas other organs such as heart, lung and muscle, showed uptake of about 5.6%, 6.4% and 2%, respectively. The complexes in this work showed a high rate of uptake in vitro, but was not reproduced in vivo model, which can be related to low concentration of the complexes inside the cells and reduced vascularity of tumor tissue, with lower intake of complex through the blood system. (author)