Effect of topography on subglacial discharge and submarine melting during tidewater glacier retreat.

-We explored secular variations in subglacial discharge and submarine melting with an idealized model -Subglacial discharge increases as tidewater glaciers retreat along retrograde beds -Submarine melting depends on subglacial discharge and therefore promotes unstable retreat on retrograde bedsTo first order, subglacial discharge depends on climate, which determines precipitation fluxes and glacier mass balance, and the rate of glacier volume change. For tidewater glaciers, large and rapid changes in glacier volume can occur independent of climate change due to strong glacier dynamic feedbacks. Using an idealized tidewater glacier model, we show that these feedbacks produce secular variations in subglacial discharge that are influenced by subglacial topography. Retreat along retrograde bed slopes (into deep water) results in rapid surface lowering and coincident increases in subglacial discharge. Consequently, submarine melting of glacier termini, which depends on subglacial discharge and ocean thermal forcing, also increases during retreat into deep water. Both subglacial discharge and submarine melting subsequently decrease as glacier termini retreat out of deep water and approach new steady state equilibria. In our simulations, subglacial discharge reached peaks that were 6–17% higher than preretreat values, with the highest values occurring during retreat from narrow sills, and submarine melting increased by 14% for unstratified fjords and 51% for highly stratified fjords. Our results therefore indicate that submarine melting acts in concert with iceberg calving to cause tidewater glacier termini to be unstable on retrograde beds. The full impact of submarine melting on tidewater glacier stability remains uncertain, however, due to poor understanding of the coupling between submarine melting and iceberg calving.Funding was provided by the National Oceanic and Atmospheric Association (NA13OAR4310098) and the U.S. National Science Foundation (PLR-1504288 and PLR-1504521).Ye

Lepton Flavour Violation in Models with A4 Flavour Symmetry

We analyze lepton flavour violating transitions, leptonic magnetic dipole moments (MDMs) and electric dipole moments (EDMs) in a class of models characterized by the flavour symmetry A4 x Z3 x U(1)_{FN}, whose choice is motivated by the approximate tri-bimaximal mixing observed in neutrino oscillations. We construct the relevant low-energy effective Lagrangian where these effects are dominated by dimension six operators, suppressed by the scale M of new physics. All the flavour breaking effects are universally described by the vacuum expectation values of a set of spurions. We separately analyze both a supersymmetric and a general case. While the observed discrepancy delta a_mu in the anomalous MDM of the muon suggests M of order of a few TeV, several data require M above 10 TeV, in particular the limit on EDM of the electron. In the general case also the present limit on BR(mu -> e gamma) requires M >10 TeV, at least. The branching ratios for mu -> e gamma, tau -> mu gamma and tau -> e gamma are all expected to be of the same order. In the supersymmetric case the constraint from mu -> e gamma is softened and it can be satisfied by a smaller scale M. In this case both the observed delta a_mu and the current bound on BR(mu -> e gamma) can be satisfied, at the price of a rather small value for ||, of the order of a few percents, that reflects on a similar value for theta_{13}.Comment: 29 pages, 1 figur

Regulators of G protein Signaling (RGS) proteins in GtoPdb v.2021.2

Regulator of G protein Signaling, or RGS, proteins serve an important regulatory role in signaling mediated by G protein-coupled receptors (GPCRs). They all share a common RGS domain that directly interacts with active, GTP-bound Gα subunits of heterotrimeric G proteins. RGS proteins stabilize the transition state for GTP hydrolysis on Gα and thus induce a conformational change in the Gα subunit that accelerates GTP hydrolysis, thereby effectively turning off signaling cascades mediated by GPCRs. This GTPase accelerating protein (GAP) activity is the canonical mechanism of action for RGS proteins, although many also possess additional functions and domains. RGS proteins are divided into four families, R4, R7, R12 and RZ based on sequence homology, domain structure as well as specificity towards Gα subunits. For reviews on RGS proteins and their potential as therapeutic targets, see e.g. [225, 529, 578, 583, 584, 742, 753, 444, 10]

Gayatry Chakravorty Spivak: Nacionalizam i imaginacija i drugi eseji

This paper contributes to the empirical evidence on participation and attainment in higher education by reviewing the patterns of entry and success of undergraduate students. It examines the characteristics of entrants to different subjects and considers the role that subject studied plays in determining the likelihood of graduating with a ‘good’ degree. The data used were drawn from the administrative records of over 38,000 UK-domiciled undergraduate students from one ‘elite’ British university. Despite considerable between-subject variation in degree outcomes, multivariate analysis of the relationship between students’ social and academic characteristics and achievement at university revealed that once social background and prior attainment had been controlled for, the subject students studied added little explanatory power to models predicting final degree classifications. Differences in degree outcome were most strongly related to attainment on entry to higher education, sex and ethnicity. In contrast with attainment during the earlier phases of education, the relationship with occupational class was relatively weak. Disparities between the proportion of higher level classifications awarded in different subjects can be largely explained by the background characteristics of the students who choose (and are accepted) to study on these degrees. This finding has particular implications for policies aimed at increasing both the number and quality of Science, Technology, Engineering and Mathematics (STEM) graduates in what is often argued to be a ‘shortage’ or ‘priority’ area

The Concise Guide to PHARMACOLOGY 2023/24:Introduction and Other Protein Targets

The Concise Guide to PHARMACOLOGY 2023/24 is the sixth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of approximately 1800 drug targets, and about 6000 interactions with about 3900 ligands. There is an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes almost 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.16176. In addition to this overview, in which are identified 'Other protein targets' which fall outside of the subsequent categorisation, there are six areas of focus: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2023, and supersedes data presented in the 2021/22, 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate.</p

THE CONCISE GUIDE TO PHARMACOLOGY 2021/22: Introduction and Other Protein Targets.

The Concise Guide to PHARMACOLOGY 2021/22 is the fifth in this series of biennial publications. The Concise Guide provides concise overviews, mostly in tabular format, of the key properties of nearly 1900 human drug targets with an emphasis on selective pharmacology (where available), plus links to the open access knowledgebase source of drug targets and their ligands (www.guidetopharmacology.org), which provides more detailed views of target and ligand properties. Although the Concise Guide constitutes over 500 pages, the material presented is substantially reduced compared to information and links presented on the website. It provides a permanent, citable, point-in-time record that will survive database updates. The full contents of this section can be found at http://onlinelibrary.wiley.com/doi/bph.15537. In addition to this overview, in which are identified 'Other protein targets' which fall outside of the subsequent categorisation, there are six areas of focus: G protein-coupled receptors, ion channels, nuclear hormone receptors, catalytic receptors, enzymes and transporters. These are presented with nomenclature guidance and summary information on the best available pharmacological tools, alongside key references and suggestions for further reading. The landscape format of the Concise Guide is designed to facilitate comparison of related targets from material contemporary to mid-2021, and supersedes data presented in the 2019/20, 2017/18, 2015/16 and 2013/14 Concise Guides and previous Guides to Receptors and Channels. It is produced in close conjunction with the Nomenclature and Standards Committee of the International Union of Basic and Clinical Pharmacology (NC-IUPHAR), therefore, providing official IUPHAR classification and nomenclature for human drug targets, where appropriate