Grifonin-1: A Small HIV-1 Entry Inhibitor Derived from the Algal Lectin, Griffithsin

Background: Griffithsin, a 121-residue protein isolated from a red algal Griffithsia sp., binds high mannose N-linked glycans of virus surface glycoproteins with extremely high affinity, a property that allows it to prevent the entry of primary isolates and laboratory strains of T- and M-tropic HIV-1. We used the sequence of a portion of griffithsin's sequence as a design template to create smaller peptides with antiviral and carbohydrate-binding properties. Methodology/Results: The new peptides derived from a trio of homologous β-sheet repeats that comprise the motifs responsible for its biological activity. Our most active antiviral peptide, grifonin-1 (GRFN-1), had an EC50 of 190.8±11.0 nM in in vitro TZM-bl assays and an EC50 of 546.6±66.1 nM in p24gag antigen release assays. GRFN-1 showed considerable structural plasticity, assuming different conformations in solvents that differed in polarity and hydrophobicity. Higher concentrations of GRFN-1 formed oligomers, based on intermolecular β-sheet interactions. Like its parent protein, GRFN-1 bound viral glycoproteins gp41 and gp120 via the N-linked glycans on their surface. Conclusion: Its substantial antiviral activity and low toxicity in vitro suggest that GRFN-1 and/or its derivatives may have therapeutic potential as topical and/or systemic agents directed against HIV-1

ARPES: A probe of electronic correlations

Angle-resolved photoemission spectroscopy (ARPES) is one of the most direct methods of studying the electronic structure of solids. By measuring the kinetic energy and angular distribution of the electrons photoemitted from a sample illuminated with sufficiently high-energy radiation, one can gain information on both the energy and momentum of the electrons propagating inside a material. This is of vital importance in elucidating the connection between electronic, magnetic, and chemical structure of solids, in particular for those complex systems which cannot be appropriately described within the independent-particle picture. Among the various classes of complex systems, of great interest are the transition metal oxides, which have been at the center stage in condensed matter physics for the last four decades. Following a general introduction to the topic, we will lay the theoretical basis needed to understand the pivotal role of ARPES in the study of such systems. After a brief overview on the state-of-the-art capabilities of the technique, we will review some of the most interesting and relevant case studies of the novel physics revealed by ARPES in 3d-, 4d- and 5d-based oxides.Comment: Chapter to appear in "Strongly Correlated Systems: Experimental Techniques", edited by A. Avella and F. Mancini, Springer Series in Solid-State Sciences (2013). A high-resolution version can be found at: http://www.phas.ubc.ca/~quantmat/ARPES/PUBLICATIONS/Reviews/ARPES_Springer.pdf. arXiv admin note: text overlap with arXiv:cond-mat/0307085, arXiv:cond-mat/020850

What Is a Decision Problem? Designing Alternatives

International audienceThis paper presents a general framework for the design of alternatives in decision problems. The paper addresses both the issue of how to design alternatives within "known decision spaces" and on how to perform the same action within "partially known or unknown decision spaces". The paper aims at providing archetypes for the design of algorithms supporting the generation of alternatives

Cognitive Defeasible Reasoning: the Extent to Which Forms of Defeasible Reasoning Correspond with Human Reasoning

Classical logic forms the basis of knowledge representation and reasoning in AI. In the real world, however, classical logic alone is insufficient to describe the reasoning behaviour of human beings. It lacks the flexibility so characteristically required of reasoning under uncer- tainty, reasoning under incomplete information and reasoning with new information, as humans must. In response, non-classical extensions to propositional logic have been formulated, to provide non-monotonicity. It has been shown in previous studies that human reasoning exhibits non- monotonicity. This work is the product of merging three independent studies, each one focusing on a different formalism for non-monotonic reasoning: KLM defeasible reasoning, AGM belief revision and KM belief update. We investigate, for each of the postulates propounded to characterise these logic forms, the extent to which they have correspondence with human reasoners. We do this via three respective experiments and present each of the postulates in concrete and abstract form. We discuss related work, our experiment design, testing and evaluation, and report on the results from our experiments. We find evidence to believe that 1 out of 5 KLM defeasible reasoning postulates, 3 out of 8 AGM belief revi- sion postulates and 4 out of 8 KM belief update postulates conform in both the concrete and abstract case. For each experiment, we performed an additional investigation. In the experiments of KLM defeasible rea- soning and AGM belief revision, we analyse the explanations given by participants to determine whether the postulates have a normative or descriptive relationship with human reasoning. We find evidence that suggests, overall, KLM defeasible reasoning has a normative relationship with human reasoning while AGM belief revision has a descriptive rela- tionship with human reasoning. In the experiment of KM belief update, we discuss counter-examples to the KM postulates

Life-Long Radar Tracking of Bumblebees

This work was supported by European Research Council Advanced Grant no. 339347

Heterogeneous melting near the Thwaites Glacier grounding line

Thwaites Glacier represents 15% of the ice discharge from the West Antarctic Ice Sheet and influences a wider catchment. Because it is grounded below sea level, Thwaites Glacier is thought to be susceptible to runaway retreat triggered at the grounding line (GL) at which the glacier reaches the ocean. Recent ice-flow acceleration2,8 and retreat of the ice front and GL indicate that ice loss will continue. The relative impacts of mechanisms underlying recent retreat are however uncertain. Here we show sustained GL retreat from at least 2011 to 2020 and resolve mechanisms of ice-shelf melt at the submetre scale. Our conclusions are based on observations of the Thwaites Eastern Ice Shelf (TEIS) from an underwater vehicle, extending from the GL to 3 km oceanward and from the ice–ocean interface to the sea floor. These observations show a rough ice base above a sea floor sloping upward towards the GL and an ocean cavity in which the warmest water exceeds 2 °C above freezing. Data closest to the ice base show that enhanced melting occurs along sloped surfaces that initiate near the GL and evolve into steep-sided terraces. This pronounced melting along steep ice faces, including in crevasses, produces stratification that suppresses melt along flat interfaces. These data imply that slope-dependent melting sculpts the ice base and acts as an important response to ocean warming