Gaussian Spectral Line Profiles of Astrophysical Masers

Calculations are performed to demonstrate the deviations from Gaussian that occur in the spectral line profiles of a linear maser as a result of the amplification process. Near-Gaussian profiles are presented for bright, interstellar 22 GHz water masers obtained from high resolution Very Long Baseline Array (VLBA) observations of W3 IRS 5. For the profiles to be so close to Gaussian, the calculations indicate that these masers must originate in quite hot gas with temperatures greater than 1200 K -- a conclusion that is supportive of C-type shocks as the origin of these masers. In addition, the degree of saturation of these masers must be less than approximately one-third, from which it follows that the beaming angles are less than about 10^{-4} ster and the actual luminosities are modest. If spectral profiles that are as close to Gaussian as the profiles presented in this initial investigation are found to occur widely, they can be valuable diagnostics for the environments of astrophysical masers.Comment: 4 pages with 3 figures embedded in paper; uses AASTEX with emulateapj5.sty; accepted for publication in ApJ (Letters

Comparison of Flow and Transport Experiments on 3D Printed Micromodels with Direct Numerical Simulations

International audienceUnderstanding pore-scale flow and transport processes is important for understanding flow and transport within rocks on a larger scale. Flow experiments on small-scale micromodels can be used to experimentally investigate pore-scale flow. Current manufacturing methods of micromodels are costly and time consuming. 3D printing is an alternative method for the production of micromodels. We have been able to visualise small-scale, single-phase flow and transport processes within a 3D printed micromodel using a custom-built visualisation cell. Results have been compared with the same experiments run on a micromodel with the same geometry made from polymethyl methacrylate (PMMA, also known as Perspex). Numerical simulations of the experiments indicate that differences in experimental results between the 3D printed micromodel and the Perspex micromodel may be due to variability in print geometry and surface properties between the samples. 3D printing technology looks promising as a micromodel manufacturing method; however, further work is needed to improve the accuracy and quality of 3D printed models in terms of geometry and surface roughness

Comparison of Flow and Transport Experiments on 3D Printed Micromodels with Direct Numerical Simulations

Understanding pore-scale flow and transport processes is important for understanding flow and transport within rocks on a larger scale. Flow experiments on small-scale micromodels can be used to experimentally investigate pore-scale flow. Current manufacturing methods of micromodels are costly and time consuming. 3D printing is an alternative method for the production of micromodels. We have been able to visualise small-scale, single-phase flow and transport processes within a 3D printed micromodel using a custom-built visualisation cell. Results have been compared with the same experiments run on a micromodel with the same geometry made from polymethyl methacrylate (PMMA, also known as Perspex). Numerical simulations of the experiments indicate that differences in experimental results between the 3D printed micromodel and the Perspex micromodel may be due to variability in print geometry and surface properties between the samples. 3D printing technology looks promising as a micromodel manufacturing method; however, further work is needed to improve the accuracy and quality of 3D printed models in terms of geometry and surface roughness

Regulation of cell survival by sphingosine-1-phosphate receptor S1P1 via reciprocal ERK-dependent suppression of bim and PI-3-kinase/protein kinase C-mediated upregulation of Mcl-1

Although the ability of bioactive lipid sphingosine-1-phosphate (S1P) to positively regulate anti-apoptotic/pro-survival responses by binding to S1P1 is well known, the molecular mechanisms remain unclear. Here we demonstrate that expression of S1P1 renders CCL39 lung fibroblasts resistant to apoptosis following growth factor withdrawal. Resistance to apoptosis was associated with attenuated accumulation of pro-apoptotic BH3-only protein Bim. However, although blockade of extracellular signal-regulated kinase (ERK) activation could reverse S1P1-mediated suppression of Bim accumulation, inhibition of caspase-3 cleavage was unaffected. Instead S1P1-mediated inhibition of caspase-3 cleavage was reversed by inhibition of phosphatidylinositol-3-kinase (PI3K) and protein kinase C (PKC), which had no effect on S1P1 regulation of Bim. However, S1P1 suppression of caspase-3 was associated with increased expression of anti-apoptotic protein Mcl-1, the expression of which was also reduced by inhibition of PI3K and PKC. A role for the induction of Mcl-1 in regulating endogenous S1P receptor-dependent pro-survival responses in human umbilical vein endothelial cells was confirmed using S1P receptor agonist FTY720-phosphate (FTY720P). FTY720P induced a transient accumulation of Mcl-1 that was associated with a delayed onset of caspase-3 cleavage following growth factor withdrawal, whereas Mcl-1 knockdown was sufficient to enhance caspase-3 cleavage even in the presence of FTY720P. Consistent with a pro-survival role of S1P1 in disease, analysis of tissue microarrays from ER+ breast cancer patients revealed a significant correlation between S1P1 expression and tumour cell survival. In these tumours, S1P1 expression and cancer cell survival were correlated with increased activation of ERK, but not the PI3K/PKB pathway. In summary, pro-survival/anti-apoptotic signalling from S1P1 is intimately linked to its ability to promote the accumulation of pro-survival protein Mcl-1 and downregulation of pro-apoptotic BH3-only protein Bim via distinct signalling pathways. However, the functional importance of each pathway is dependent on the specific cellular context

The Paradoxes of Recovery Policy: Exploring the Impact of Austerity and Responsibilisation for the Citizenship Claims of People with Drug Problems

This article critically examines the implications accompanying the introduction and implementation of recovery-based policy. The article draws upon research conducted in Lancashire, England, where commissioners have been at the forefront of recent developments in ‘whole system’ models of commissioning. Empirical data are drawn on to make a series of new arguments about the tensions and practice implications of the new recovery agenda. The article has three main objectives. First, it explores current shifts in England, in which drug service commissioning has moved from being centrally funded and directed, to locally determined. Second, it references the rise of the well-informed user in the reconfigured landscape of recovery and the ways in which commissioning models may enhance or negate the contribution of user activists to local cultures of recovery. Third, it references the changing political context, in which austerity is being used to increase the pressure on provider services to demonstrate social value, utility and effectiveness. The article argues that there is a palpable need to re-politicize drug debates and recognize the structural and demographic factors which frame problem drug use, as well as the social and cultural factors which support or negate their opportunities for recovery

LC-ESI-MS/MS profiling of phenolics from Eleutherococcus spp. inflorescences, structure-activity relationship as antioxidants, inhibitors of hyaluronidase and acetylcholinesterase

AbstractNature is a source of many plant-based molecules used as pro- or drugs. Eleutherococcus species are native to Asia and the North Russia, and are traditionally used to treat various diseases. In turn, neither secondary metabolites of the species cultivated in the West Europe nor the bioactivity is known. No differences in the phenols and flavonoids content in the inflorescences were found. The richest in polyphenols was E. giraldii (5.18mg/g), while in flavonoids it was E. gracilistylus (1.80mg/g). Using LC-ESI-MS/MS, protocatechuic and trans-caffeic acids have been identified as the most abundant compounds in E. gracilistylus, E. giraldii, E. senticosus (833.4; 855.6; 614.7 and 280.8; 156.0; 167.6μg/g DE). It was observed that all species were able to chelate Fe2+ with the EC50 value of 0.2, 0.6, 0.3mg/mL for E. gracilistylus, E. giraldii, E. senticosus, respectively. E. gracilistylus exhibited the strongest antiperoxidation and anti-DPPH∗ activity (EC50 3.2 and 0.48mg/mL). The weak inhibitory potential has been observed in case of AChE inhibition at the level of 16.17 and 12.2% for E. gracilistylus, E. giraldii. We report for the first time that the extracts inhibited Hyal activity in the range from 16.4 to 60.7%. To our best knowledge, no information was available on this activity of the inflorescences and this provides a background to study inflorescences in more detail. Considering the SAR, an antioxidant activity may be correlated with a high amount of protocatechuic and trans-caffeic acids and their chemical structure

Translocation, switching and gating: potential roles for ATP in long-range communication on DNA by Type III restriction endonucleases

To cleave DNA, the Type III RM (restriction–modification) enzymes must communicate the relative orientation of two recognition sequences, which may be separated by many thousands of base pairs. This long-range interaction requires ATP hydrolysis by a helicase domain, and both active (DNA translocation) and passive (DNA sliding) modes of motion along DNA have been proposed. Potential roles for ATP binding and hydrolysis by the helicase domains are discussed, with a focus on bipartite ATPases that act as molecular switches

Close communications: Hedge funds, brokers and the emergence of herding

We examine how communication, evaluation and decision-making practices among competing market actors contribute to the establishment of herding and whether this has impact on market wide phenomena such as prices and risk. Data is collected from interviews and observations with hedge fund industry participants in Europe, the United States and Asia. We examine both contemporaneous and biographical data, finding that decision making relies on an elaborate two-tiered structure of connections among hedge fund managers and between them and brokers. This structure is underpinned by idea sharing and development between competing hedge funds leading to ‘expertisebased’ herding and an increased probability of over-embeddedness. We subsequently present a case study demonstrating the role that communication between competing hedge funds plays in the creation of herding and show that such trades affect prices by introducing an additional risk: the disregarding of information from sources outside the trusted connections

Combinations of physiologic estrogens with xenoestrogens alter calcium and kinase responses, prolactin release, and membrane estrogen receptor trafficking in rat pituitary cells

<p>Abstract</p> <p>Background</p> <p>Xenoestrogens such as alkylphenols and the structurally related plastic byproduct bisphenol A have recently been shown to act potently via nongenomic signaling pathways and the membrane version of estrogen receptor-α. Though the responses to these compounds are typically measured individually, they usually contaminate organisms that already have endogenous estrogens present. Therefore, we used quantitative medium-throughput screening assays to measure the effects of physiologic estrogens in combination with these xenoestrogens.</p> <p>Methods</p> <p>We studied the effects of low concentrations of endogenous estrogens (estradiol, estriol, and estrone) at 10 pM (representing pre-development levels), and 1 nM (representing higher cycle-dependent and pregnancy levels) in combinations with the same levels of xenoestrogens in GH₃/B6/F10 pituitary cells. These levels of xenoestrogens represent extremely low contamination levels. We monitored calcium entry into cells using Fura-2 fluorescence imaging of single cells. Prolactin release was measured by radio-immunoassay. Extracellular-regulated kinase (1 and 2) phospho-activations and the levels of three estrogen receptors in the cell membrane (ERα, ERβ, and GPER) were measured using a quantitative plate immunoassay of fixed cells either permeabilized or nonpermeabilized (respectively).</p> <p>Results</p> <p>All xenoestrogens caused responses at these concentrations, and had disruptive effects on the actions of physiologic estrogens. Xenoestrogens reduced the % of cells that responded to estradiol via calcium channel opening. They also inhibited the activation (phosphorylation) of extracellular-regulated kinases at some concentrations. They either inhibited or enhanced rapid prolactin release, depending upon concentration. These latter two dose-responses were nonmonotonic, a characteristic of nongenomic estrogenic responses.</p> <p>Conclusions</p> <p>Responses mediated by endogenous estrogens representing different life stages are vulnerable to very low concentrations of these structurally related xenoestrogens. Because of their non-classical dose-responses, they must be studied in detail to pinpoint effective concentrations and the directions of response changes.</p