Peptide binding to the HLA-DRB1 supertype:a proteochemometrics analysis

A proteochemometrics approach was applied to a set of 2666 peptides binding to 12 HLA-DRB1 proteins. Sequences of both peptide and protein were described using three z-descriptors. Cross terms accounting for adjacent positions and for every second position in the peptides were included in the models, as well as cross terms for peptide/protein interactions. Models were derived based on combinations of different blocks of variables. These models had moderate goodness of fit, as expressed by r2, which ranged from 0.685 to 0.732; and good cross-validated predictive ability, as expressed by q2, which varied from 0.678 to 0.719. The external predictive ability was tested using a set of 356 HLA-DRB1 binders, which showed an r2(pred) in the range 0.364-0.530. Peptide and protein positions involved in the interactions were analyzed in terms of hydrophobicity, steric bulk and polarity.

The second intracellular loop of the calcitonin gene-related peptide receptor provides molecular determinants for signal transduction and cell surface expression

The calcitonin gene-related peptide (CGRP) receptor is a heterodimer of a family B G-protein-coupled receptor, calcitonin receptor-like receptor (CLR), and the accessory protein receptor activity modifying protein 1. It couples to Gs, but it is not known which intracellular loops mediate this. We have identified the boundaries of this loop based on the relative position and length of the juxtamembrane transmembrane regions 3 and 4. The loop has been analyzed by systematic mutagenesis of all residues to alanine, measuring cAMP accumulation, CGRP affinity, and receptor expression. Unlike rhodopsin, ICL2 of the CGRP receptor plays a part in the conformational switch after agonist interaction. His-216 and Lys-227 were essential for a functional CGRP-induced cAMP response. The effect of (H216A)CLR is due to a disruption to the cell surface transport or surface stability of the mutant receptor. In contrast, (K227A)CLR had wild-type expression and agonist affinity, suggesting a direct disruption to the downstream signal transduction mechanism of the CGRP receptor. Modeling suggests that the loop undergoes a significant shift in position during receptor activation, exposing a potential G-protein binding pocket. Lys-227 changes position to point into the pocket, potentially allowing it to interact with bound G-proteins. His-216 occupies a position similar to that of Tyr-136 in bovine rhodopsin, part of the DRY motif of the latter receptor. This is the first comprehensive analysis of an entire intracellular loop within the calcitonin family of G-protein-coupled receptor. These data help to define the structural and functional characteristics of the CGRP-receptor and of family B G-protein-coupled receptors in general. © 2006 by The American Society for Biochemistry and Molecular Biology, Inc.

Back from the future:the second chance in the past of aller + infinitive

Typological studies (Bybee et al. 1994, Dahl 2000, Bourdin 2008 among many others) have shown a tendency for spatial elements (such as movement verbs) to grammaticalise into temporal expressions. The periphrasis made of aller + infinitive has been very productive in Romance languages. If in French, Spanish or Portuguese, it refers to future, it refers to a simple past in Catalan. fr.: je vais aller au cinéma esp.: voy a ir al cine pt. Vou ira o cine cat.: vaig anar al cine Barceló & Bres (2005:168) indicate that, In French, «vers le XVIème siècle, […] la périphrase a brièvement fonctionné comme un temps du passé (alors même que l’emploi comme temps du futur émergeait)»: (1) Sur ces propos, firent leur accord et, en regardant le lieu le plus propre pour faire cette belle œuvre, elle va dire qu’elle n’en savait point de meilleure ni plus loin de tout soupçon, qu’une petite maison qui était dedans le parc, où il y avait chambre et lit tout à propos. (Marguerite de Navarre, L’Heptaméron) The future value took over so much so that Damourette & Pichon (1911-1936 :117) claimed the past value had disappeared»: Un second tour, encore plus aberrant, n’a plus, que nous sachions, aucune position en pays d’Oui. Nous voulons parler de l’expression d’un passé au moyen de l’auxiliaire aller, suivi de l’infinitif. Ce tour a eu une grande fortune dans le provençal ancien et le catalan […] En français, on n’en trouve que des traces, notamment du XIVe au XVIe siècles . Ex.:[…] Adoncques s’arrêtèrent le conte et Raimondin soubz un grand arbre ; lors va dire le conte à Raimondin: […]. Et Raimondin va lui dire : Sire, ce qu’il vous plaira. That allegedly extinct use is nonetheless alive and kicking in Contemporary French. Larreya (2005:349)notes that it is « très courant dans les récits – en particulier dans les récits oraux» and it is also found in newspaper language as shown by this except from an obituary for Loulou Gasté (Le Monde 1995): (2) Celle-ci se déroule aux Editions Micro, où il a un bureau. Séduit par la jeune interprète, il commence à lui écrire des chansons sur mesure et leur complicité va mettre cinq ans à se transformer en amour. Au début de leur rencontre, Loulou est neurasthénique parce qu’il vient de divorcer et la future Line, exclusivement préoccupée par son métier, ne songe à rien d’autre. Line et Loulou vont rattraper le temps perdu et créer ensemble un millier de petites chansons dont la plupart sont devenues immortelles. Jusqu’à ces derniers mois, il ne va pas se passer une journée sans que Loulou s’empare de sa guitare pour créer un refrain. Would we be witnessing a linguistic resurrection? The same structure seems therefore to have grammaticalised in diverging and even diametrically opposite ways in different Romance languages. In this talk, we shall try to explain how the phrase aller + infinitive is able to function both as a future and a past. We will especially concentrate on the case of contemporary French where, while the future interpretation has obtained the status of tense as futur proche or périphrastique, a past interpretation is now commonplace. Our reflection will be supported by a personal corpus of authentic examples.

Surviving in violent conflicts: Chinese interpreters in the second Sino-Japanese War (1931-1945)

In the past decade interpreting studies has gradually adopted a sociological perspective, taking into account social and cultural factors that affect interpreters actual behaviour in different settings. However, there have been few studies of interpreters practices as forms of social interaction, especially of the ways in which they become professionals and operate as social agents. Drawing upon Pierre Bourdieus theory of practice, this thesis aims to offer a contribution to the history of interpreting by examining the professional training and practices of Chinese interpreters during the Second Sino-Japanese War (1931-1945). On the basis of Bourdieus concept of field, this thesis reconstructs three competing fields dominated by three political and military powers: the Chinese Kuomingtang (KMT) government, the Chinese Communist Party, and the Japanese forces. By investigating interpreters training, employment and practices within these three fields, the thesis examines how the interpreting profession was affected by shifts in foreign policy, and how interpreters professional habitus were formed through their training and interaction with other social agents and institutions. It then highlights the interpreters active position-taking in pursuit of individual interests by examining particular interpreters career development through case studies of two interpreters, Xia Wenyun and Yan Jiarui, who served the Japanese forces and the Chinese KMT government, respectively. The study shows that the practices of the interpreters were broader than the scope of language transfer. In order to survive violent conflicts, interpreters often intertwined their interpreting with other political and professional activities. For them, interpreting was not a mere linguistic practice, but a strategy for self-protection, a route to power, or just a chance for a better life. Frequently crossing social, political and military borders, interpreters sometimes played a crucial cushioning role by protecting local residents from loss of life and property during the war.

Mach bands and multiscale models of spatial vision:the role of first, second, and third derivative operators in encoding bars and edges

Ernst Mach observed that light or dark bands could be seen at abrupt changes of luminance gradient in the absence of peaks or troughs in luminance. Many models of feature detection share the idea that bars, lines, and Mach bands are found at peaks and troughs in the output of even-symmetric spatial filters. Our experiments assessed the appearance of Mach bands (position and width) and the probability of seeing them on a novel set of generalized Gaussian edges. Mach band probability was mainly determined by the shape of the luminance profile and increased with the sharpness of its corners, controlled by a single parameter (n). Doubling or halving the size of the images had no significant effect. Variations in contrast (20%-80%) and duration (50-300 ms) had relatively minor effects. These results rule out the idea that Mach bands depend simply on the amplitude of the second derivative, but a multiscale model, based on Gaussian-smoothed first- and second-derivative filtering, can account accurately for the probability and perceived spatial layout of the bands. A key idea is that Mach band visibility depends on the ratio of second- to first-derivative responses at peaks in the second-derivative scale-space map. This ratio is approximately scale-invariant and increases with the sharpness of the corners of the luminance ramp, as observed. The edges of Mach bands pose a surprisingly difficult challenge for models of edge detection, but a nonlinear third-derivative operation is shown to predict the locations of Mach band edges strikingly well. Mach bands thus shed new light on the role of multiscale filtering systems in feature coding. © 2012 ARVO.

Foveation time measure in Congenital Nystagmus through second order approximation of the slow phases

Congenital Nystagmus (CN) is an ocular-motor disorder characterised by involuntary, conjugated ocular oscillations, and its pathogenesis is still unknown. The pathology is de fined as "congenital" from the onset time of its arise which could be at birth or in the first months of life. Visual acuity in CN subjects is often diminished due to nystagmus continuous oscillations, mainly on the horizontal plane, which disturb image fixation on the retina. However, during short periods in which eye velocity slows down while the target image is placed onto the fovea (called foveation intervals) the image of a given target can still be stable, allowing a subject to reach a higher visual acuity. In CN subjects, visual acuity is usually assessed both using typical measurement techniques (e.g. Landolt C test) and with eye movement recording in different gaze positions. The offline study of eye movement recordings allows physicians to analyse nystagmus main features such as waveform shape, amplitude and frequency and to compute estimated visual acuity predictors. This analytical functions estimates the best corrected visual acuity using foveation time and foveation position variability, hence a reliable estimation of this two parameters is a fundamental factor in assessing visual acuity. This work aims to enhance the foveation time estimation in CN eye movement recording, computing a second order approximation of the slow phase components of nystag-mus oscillations. About 19 infraredoculographic eye-movement recordings from 10 CN subjects were acquired and the visual acuity assessed with an acuity predictor was compared to the one measured in primary position. Results suggest that visual acuity measurements based on foveation time estimation obtained from interpolated data are closer to value obtained during Landolt C tests. © 2010 IEEE.