A search for ortho-benzyne (o-C6H4) in CRL 618

Polycyclic aromatic hydrocarbons (PAHs) have been proposed as potential carriers of the unidentified infrared bands (UIRs) and the diffuse interstellar bands (DIBs). PAHs are not likely to form by gas-phase or solid-state interstellar chemistry, but rather might be produced in the outflows of carbon-rich evolved stars. PAHs could form from acetylene addition to the phenyl radical (C6H5), which is closely chemically related to benzene (C6H6) and ortho-benzyne (o-C6H4). To date, circumstellar chemical models have been limited to only a partial treatment of benzene-related chemistry, and so the expected abundances of these species are unclear. A detection of benzene has been reported in the envelope of the proto-planetary nebula (PPN) CRL 618, but no other benzene-related species has been detected in this or any other source. The spectrum of o-C6H4 is significantly simpler and stronger than that of C6H5, and so we conducted deep Ku-, K- and Q-band searches for o-C6H4 with the Green Bank Telescope. No transitions were detected, but an upper limit on the column density of 8.4x10^13 cm^-2 has been determined. This limit can be used to constrain chemical models of PPNe, and this study illustrates the need for complete revision of these models to include the full set of benzene-related chemistry.Comment: 13 pages, 4 figures, to be published in The Astrophysical Journal Letter

Association of Basal Hyperglucagonemia with Impaired Glucagon Counterregulation in Type 1 Diabetes

Glucagon counterregulation (GCR) protects against hypoglycemia, but is impaired in type 1 diabetes (T1DM). A model-based analysis of in vivo animal data predicts that the GCR defects are linked to basal hyperglucagonemia. To test this hypothesis we studied the relationship between basal glucagon (BasG) and the GCR response to hypoglycemia in 29 hyperinsulinemic clamps in T1DM patients. Glucose levels were stabilized in euglycemia and then steadily lowered to 50 mg/dL. Glucagon was measured before induction of hypoglycemia and at 10 min intervals after glucose reached levels below 70 mg/dL. GCR was assessed by CumG, the cumulative glucagon levels above basal; MaxG, the maximum glucagon response; and RIG, the relative increase in glucagon over basal. Analysis of the results was performed with our mathematical model of GCR. The model describes interactions between islet peptides and glucose, reproduces the normal GCR axis and its impairment in diabetes. It was used to identify a control mechanism consistent with the observed link between BasG and GCR. Analysis of the clinical data showed that higher BasG was associated with lower GCR response. In particular, CumG and RIG correlated negatively with BasG (r = −0.46, p = 0.012 and r = −0.74, p < 0.0001 respectively) and MaxG increased linearly with BasG at a rate less than unity (p < 0.001). Consistent with these results was a model of GCR in which the secretion of glucagon has two components. The first is under (auto) feedback control and drives a pulsatile GCR and the second is feedback independent (basal secretion) and its increase suppresses the GCR. Our simulations showed that this model explains the observed relationships between BasG and GCR during a three-fold simulated increase in BasG. Our findings support the hypothesis that basal hyperglucagonemia contributes to the GCR impairment in T1DM and show that the predictive power of our GCR animal model applies to human pathophysiology in T1DM

Optimizing postprandial glucose management in adults with insulin-requiring diabetes: Report and recommendations

Faster-acting insulins, new noninsulin drug classes, more flexible insulin-delivery systems, and improved continuous glucose monitoring devices offer unprecedented opportunities to improve postprandial glucose (PPG) management and overall care for adults with insulin-treated diabetes. These developments led the Endocrine Society to convene a working panel of diabetes experts in December 2018 to assess the current state of PPG management, identify innovative ways to improve self-management and quality of life, and align best practices to current and emerging treatment and monitoring options. Drawing on current research and collective clinical experience, we considered the following issues for the ∼200 million adults worldwide with type 1 and insulin-requiring type 2 diabetes: (i) the role of PPG management in reducing the risk of diabetes complications; (ii) barriers preventing effective PPG management; (iii) strategies to reduce PPG excursions and improve patient quality of life; and (iv) education and clinical tools to support endocrinologists in improving PPG management. We concluded that managing PPG to minimize or prevent diabetes-related complications will require elucidating fundamental questions about optimal ways to quantify and clinically assess the metabolic dysregulation and consequences of the abnormal postprandial state in diabetes and recommend research strategies to address these questions. We also identified practical strategies and tools that are already available to reduce barriers to effective PPG management, optimize use of new and emerging clinical tools, and improve patient self-management and quality of life

Hele-Shaw beach creation by breaking waves: a mathematics-inspired experiment

Fundamentals of nonlinear wave-particle interactions are studied experimentally in a Hele-Shaw configuration with wave breaking and a dynamic bed. To design this configuration, we determine, mathematically, the gap width which allows inertial flows to survive the viscous damping due to the side walls. Damped wave sloshing experiments compared with simulations confirm that width-averaged potential-flow models with linear momentum damping are adequately capturing the large scale nonlinear wave motion. Subsequently, we show that the four types of wave breaking observed at real-world beaches also emerge on Hele-Shaw laboratory beaches, albeit in idealized forms. Finally, an experimental parameter study is undertaken to quantify the formation of quasi-steady beach morphologies due to nonlinear, breaking waves: berm or dune, beach and bar formation are all classified. Our research reveals that the Hele-Shaw beach configuration allows a wealth of experimental and modelling extensions, including benchmarking of forecast models used in the coastal engineering practice, especially for shingle beaches

Accurate Estimates of Microarray Target Concentration from a Simple Sequence-Independent Langmuir Model

Background: Microarray technology is a commonly used tool for assessing global gene expression. Many models for estimation of target concentration based on observed microarray signal have been proposed, but, in general, these models have been complex and platform-dependent. Principal Findings: We introduce a universal Langmuir model for estimation of absolute target concentration from microarray experiments. We find that this sequence-independent model, characterized by only three free parameters, yields excellent predictions for four microarray platforms, including Affymetrix, Agilent, Illumina and a custom-printed microarray. The model also accurately predicts concentration for the MAQC data sets. This approach significantly reduces the computational complexity of quantitative target concentration estimates. Conclusions: Using a simple form of the Langmuir isotherm model, with a minimum of parameters and assumptions, and without explicit modeling of individual probe properties, we were able to recover absolute transcript concentrations with high R 2 on four different array platforms. The results obtained here suggest that with a ‘‘spiked-in’ ’ concentration serie

Age and helium content of the open cluster NGC 6791 from multiple eclipsing binary members. II. age dependencies and new insights

Models of stellar structure and evolution can be constrained by measuring accurate parameters of detached eclipsing binaries in open clusters. Multiple binary stars provide the means to determine helium abundances in these old stellar systems, and in turn, to improve estimates of their age. In the first paper of this series, we demonstrated how measurements of multiple eclipsing binaries in the old open cluster NGC6791 sets tighter constraints on the properties of stellar models than has previously been possible, thereby potentially improving both the accuracy and precision of the cluster age. Here we add additional constraints and perform an extensive model comparison to determine the best estimates of the cluster age and helium content, employing as many observational constraints as possible. We improve our photometry and correct empirically for differential reddening effects. We then perform an extensive comparison of the CMDs and eclipsing binary measurements to Victoria and DSEP isochrones to estimate cluster parameters. We also reanalyse a spectrum of the star 2-17 to improve [Fe/H] constraints. We find a best estimate of the age of ~8.3 Gyr while demonstrating that remaining age uncertainty is dominated by uncertainties in the CNO abundances. The helium mass fraction is well constrained at Y = 0.30 \pm 0.01 resulting in dY/dZ ~ 1.4 assuming that such a relation exists. During the analysis we firmly identify blue straggler stars, including the star 2-17, and find indications for the presence of their evolved counterparts. Our analysis supports the RGB mass-loss found from asteroseismology and we determine precisely the absolute mass of stars on the lower RGB, 1.15\pm0.02Msun. This will be an important consistency check for the detailed asteroseismology of cluster stars.Comment: 18 Pages, 9 Figures, accepted for publication in A&

T cell subpopulations in lymph nodes may not be predictive of patient outcome in colorectal cancer

<p>Abstract</p> <p>Background</p> <p>The immune response has been proposed to be an important factor in determining patient outcome in colorectal cancer (CRC). Previous studies have concentrated on characterizing T cell populations in the primary tumour where T cells with regulatory effect (Foxp3+ Tregs) have been identified as both enhancing and diminishing anti-tumour immune responses. No previous studies have characterized the T cell response in the regional lymph nodes in CRC.</p> <p>Methods</p> <p>Immunohistochemistry was used to analyse CD4, CD8 or Foxp3+ T cell populations in the regional lymph nodes of patients with stage II CRC (n = 31), with (n = 13) or without (n = 18) cancer recurrence after 5 years of follow up, to determine if the priming environment for anti-tumour immunity was associated with clinical outcome.</p> <p>Results</p> <p>The proportions of CD4, CD8 or Foxp3+ cells in the lymph nodes varied widely between and within patients, and there was no association between T cell populations and cancer recurrence or other clinicopathological characteristics.</p> <p>Conclusions</p> <p>These data indicate that frequency of these T cell subsets in lymph nodes may not be a useful tool for predicting patient outcome.</p

Estimating Grizzly and Black Bear Population Abundance and Trend in Banff National Park Using Noninvasive Genetic Sampling

We evaluated the potential of two noninvasive genetic sampling methods, hair traps and bear rub surveys, to estimate population abundance and trend of grizzly (Ursus arctos) and black bear (U. americanus) populations in Banff National Park, Alberta, Canada. Using Huggins closed population mark-recapture models, we obtained the first precise abundance estimates for grizzly bears ( = 73.5, 95% CI = 64–94 in 2006;  = 50.4, 95% CI = 49–59 in 2008) and black bears ( = 62.6, 95% CI = 51–89 in 2006;  = 81.8, 95% CI = 72–102 in 2008) in the Bow Valley. Hair traps had high detection rates for female grizzlies, and male and female black bears, but extremely low detection rates for male grizzlies. Conversely, bear rubs had high detection rates for male and female grizzlies, but low rates for black bears. We estimated realized population growth rates, lambda, for grizzly bear males ( = 0.93, 95% CI = 0.74–1.17) and females ( = 0.90, 95% CI = 0.67–1.20) using Pradel open population models with three years of bear rub data. Lambda estimates are supported by abundance estimates from combined hair trap/bear rub closed population models and are consistent with a system that is likely driven by high levels of human-caused mortality. Our results suggest that bear rub surveys would provide an efficient and powerful means to inventory and monitor grizzly bear populations in the Central Canadian Rocky Mountains