Rings of skew polynomials and Gel'fand-Kirillov conjecture for quantum groups

We introduce and study action of quantum groups on skew polynomial rings and related rings of quotients. This leads to a ``q-deformation'' of the Gel'fand-Kirillov conjecture which we partially prove. We propose a construction of automorphisms of certain non-commutaive rings of quotients coming from complex powers of quantum group generators; this is applied to explicit calculation of singular vectors in Verma modules over U_{q}(\gtsl_{n+1}). We finally give a definition of a $q-$connection with coefficients in a ring of skew polynomials and study the structure of quantum group modules twisted by a $q-$connection.Comment: 25 page

Resolving distinct molecular origins for copper effects on PAI-1

© 2017, The Author(s). Components of the fibrinolytic system are subjected to stringent control to maintain proper hemostasis. Central to this regulation is the serpin plasminogen activator inhibitor-1 (PAI-1), which is responsible for specific and rapid inhibition of fibrinolytic proteases. Active PAI-1 is inherently unstable and readily converts to a latent, inactive form. The binding of vitronectin and other ligands influences stability of active PAI-1. Our laboratory recently observed reciprocal effects on the stability of active PAI-1 in the presence of transition metals, such as copper, depending on the whether vitronectin was also present (Thompson et al. Protein Sci 20:353–365, 2011). To better understand the molecular basis for these copper effects on PAI-1, we have developed a gel-based copper sensitivity assay that can be used to assess the copper concentrations that accelerate the conversion of active PAI-1 to a latent form. The copper sensitivity of wild-type PAI-1 was compared with variants lacking N-terminal histidine residues hypothesized to be involved in copper binding. In these PAI-1 variants, we observed significant differences in copper sensitivity, and these data were corroborated by latency conversion kinetics and thermodynamics of copper binding by isothermal titration calorimetry. These studies identified a copper-binding site involving histidines at positions 2 and 3 that confers a remarkable stabilization of PAI-1 beyond what is observed with vitronectin alone. A second site, independent from the two histidines, binds metal and increases the rate of the latency conversion

MUC1 Is a Downstream Target of STAT3 and Regulates Lung Cancer Cell Survival and Invasion

Signal transducer and activator of transcription 3 (STAT3) is aberrantly activated in human cancer including lung cancer and has been implicated in transformation, tumorigenicity, and metastasis. One putative downstream gene regulated by Stat3 is MUC1 which also has important roles in tumorigenesis. We determined if Stat3 regulates MUC1 in lung cancer cell lines and what function MUC1 plays in lung cancer cell biology. We examined MUC1 expression in non-small cell lung cancer (NSCLC) cell lines and found high levels of MUC1 protein expression associated with higher levels of tyrosine phosphorylated STAT3. STAT3 knockdown downregulated MUC1 expression whereas constitutive STAT3 expression increased MUC1 expression at mRNA and protein levels. MUC1 knockdown induced cellular apoptosis concomitant with reduced Bcl-XL and sensitized cells to cisplatin treatment. MUC1 knockdown inhibited tumor growth and metastasis in an orthotopic mouse model of lung cancer by activating apoptosis and inhibiting cell proliferation in vivo. These results demonstrate that constitutively activated STAT3 regulates expression of MUC1, which mediates lung cancer cell survival and metastasis in vitro and in vivo. MUC1 appears to be a cooperating oncoprotein with multiple oncogenic tyrosine kinase pathways and could be an effective target for the treatment of lung cancer

A method for continuous239Pu determinations in Arctic and Antarctic ice cores

Atmospheric nuclear weapons testing (NWT) resulted in the injection of plutonium (Pu) into the atmosphere and subsequent global deposition. We present a new method for continuous semi-quantitative measurement of 239Pu in ice cores, which was used to develop annual records of fallout from NWT in ten ice cores from Greenland and Antarctica. The 239Pu was measured directly using an Inductively Coupled Plasma – Sector Field Mass Spectrometer, thereby reducing analysis time and increasing depth-resolution with respect to previous methods. To validate this method, we compared our one year averaged results to published 239Pu records and other records of NWT. The 239Pu profiles from four Arctic ice cores reflected global trends in NWT and were in agreement with discrete Pu profiles from lower latitude ice cores. The 239Pu measurements in the Antarctic ice cores tracked low latitude NWT, consistent with previously published discrete records from Antarctica. Advantages of the continuous 239Pu measurement method are (1) reduced sample preparation and analysis time; (2) no requirement for additional ice samples for NWT fallout determinations; (3) measurements are exactly co-registered with all other chemical, elemental, isotopic, and gas measurements from the continuous analytical system; and (4) the long half-life means the 239Pu record is stable through time

High sensitivity of summer temperatures to stratospheric sulfur loading from volcanoes in the Northern Hemisphere

This work was funded by an ERC (European Research Council) Marie Curie Career Integration Grant (CIG14-631752) and a Philip Leverhulme prize in Earth Sciences (PLP-2021-167) from the Leverhulme Trust awarded to A.B. WH is funded by a UKRI Future Leaders Fellowship (MR/S033505/1). M.S. acknowledges the support of the ERC under the European Union’s Horizon 2020 research and innovation programme (grant agreement 820047). H.M.I. and L.C. were both funded by IAPETUS and IAPETUS2 NERC Doctoral Training Partnership. The Tunu2013 and NEEM_2011_S1 ice cores were collected and analyzed for sulfur and other chemical species used to establish the ice core chronologies with funding from NSF grants 1204176 and 0909541 to J.R.M., respectively, and ice cores were sampled with funding from NSF grant 1340174.The 540s, 1450s, and 1600s represent three of the five coldest decades in the Common Era (CE). In each of these cases, the cause of these cold pulses has been attributed to large volcanic eruptions. However, the provenance of the eruption and magnitude of the volcanic forcing remains uncertain. Here, we use high-resolution sulfur isotopes in Greenland and Antarctic ice cores measured across these events to provide a means of improving sulfur loading estimates for these eruptions. In each case, the largest reconstructed tree-ring cooling is associated with an extratropical eruption, and the high-altitude stratospheric sulfate loading of these events is substantially smaller than previous estimates (by up to a factor of two). These results suggest an increased sensitivity of the reconstructed Northern Hemisphere summer temperature response to extratropical eruptions. This highlights the importance of climate feedbacks and processes that amplify and prolong the cooling signal from high latitudes, such as changes in sea ice extent and ocean heat content.Publisher PDFPeer reviewe

Coronary artery endothelial dysfunction is positively correlated with low density lipoprotein and inversely correlated with high density lipoprotein subclass particles measured by nuclear magnetic resonance spectroscopy.

OBJECTIVE: The association between cholesterol and endothelial dysfunction remains controversial. We tested the hypothesis that lipoprotein subclasses are associated with coronary endothelial dysfunction. METHODS AND RESULTS: Coronary endothelial function was assessed in 490 patients between November 1993 and February 2007. Fasting lipids and nuclear magnetic resonance (NMR) lipoprotein particle subclasses were measured. There were 325 females and 165 males with a mean age of 49.8+/-11.6 years. Coronary endothelial dysfunction (epicardial constriction>20% or increase in coronary blood flow<50% in response to intracoronary acetylcholine) was diagnosed in 273 patients, the majority of whom (64.5%) had microvascular dysfunction. Total cholesterol and LDL-C (low density lipoprotein cholesterol) were not associated with endothelial dysfunction. One-way analysis and multivariate methods adjusting for age, gender, diabetes, hypertension and lipid-lowering agent use were used to determine the correlation between lipoprotein subclasses and coronary endothelial dysfunction. Epicardial endothelial dysfunction was significantly correlated with total (p=0.03) and small LDLp (LDL particles) (p<0.01) and inversely correlated with total and large HDLp (high density lipoprotein particles) (p<0.01). CONCLUSIONS: Epicardial, but not microvascular, coronary endothelial dysfunction was associated directly with LDL particles and inversely with HDL particles, suggesting location-dependent impact of lipoprotein particles on the coronary circulation

Elevation change of the Greenland Ice Sheet due to surface mass balance and firn processes, 1960–2014

© The Author(s), 2015. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in The Cryosphere 9 (2015): 2009-2025, doi:10.5194/tc-9-2009-2015.Observed changes in the surface elevation of the Greenland Ice Sheet are caused by ice dynamics, basal elevation change, basal melt, surface mass balance (SMB) variability, and by compaction of the overlying firn. The last two contributions are quantified here using a firn model that includes compaction, meltwater percolation, and refreezing. The model is forced with surface mass fluxes and temperature from a regional climate model for the period 1960–2014. The model results agree with observations of surface density, density profiles from 62 firn cores, and altimetric observations from regions where ice-dynamical surface height changes are likely small. In areas with strong surface melt, the firn model overestimates density. We find that the firn layer in the high interior is generally thickening slowly (1–5 cm yr−1). In the percolation and ablation areas, firn and SMB processes account for a surface elevation lowering of up to 20–50 cm yr−1. Most of this firn-induced marginal thinning is caused by an increase in melt since the mid-1990s and partly compensated by an increase in the accumulation of fresh snow around most of the ice sheet. The total firn and ice volume change between 1980 and 2014 is estimated at −3295 ± 1030 km3 due to firn and SMB changes, corresponding to an ice-sheet average thinning of 1.96 ± 0.61 m. Most of this volume decrease occurred after 1995. The computed changes in surface elevation can be used to partition altimetrically observed volume change into surface mass balance and ice-dynamically related mass changes.P. Kuipers Munneke received financial support from the Netherlands Polar Programme (NPP) of the Netherlands Institute for Scientific Research (NWO). ECMWF at Reading (UK) is acknowledged for use of the Cray supercomputing system. The J. E. Box contribution is supported by Det Frie Forskningsråd grant 4002-00234 and Geocenter Denmark