Using X-ray Crystallography, Biophysics, and Functional Assays to Determine the Mechanisms Governing T-cell Receptor Recognition of Cancer Antigens.

Human CD8+ cytotoxic T lymphocytes (CTLs) are known to play an important role in tumor control. In order to carry out this function, the cell surface-expressed T-cell receptor (TCR) must functionally recognize human leukocyte antigen (HLA)-restricted tumor-derived peptides (pHLA). However, we and others have shown that most TCRs bind sub-optimally to tumor antigens. Uncovering the molecular mechanisms that define this poor recognition could aid in the development of new targeted therapies that circumnavigate these shortcomings. Indeed, present therapies that lack this molecular understanding have not been universally effective. Here, we describe methods that we commonly employ in the laboratory to determine how the nature of the interaction between TCRs and pHLA governs T-cell functionality. These methods include the generation of soluble TCRs and pHLA and the use of these reagents for X-ray crystallography, biophysical analysis, and antigen-specific T-cell staining with pHLA multimers. Using these approaches and guided by structural analysis, it is possible to modify the interaction between TCRs and pHLA and to then test how these modifications impact T-cell antigen recognition. These findings have already helped to clarify the mechanism of T-cell recognition of a number of cancer antigens and could direct the development of altered peptides and modified TCRs for new cancer therapies

Dynamical control of correlated states in a square quantum dot

In the limit of low particle density, electrons confined to a quantum dot form strongly correlated states termed Wigner molecules, in which the Coulomb interaction causes the electrons to become highly localized in space. By using an effective model of Hubbard-type to describe these states, we investigate how an oscillatory electric field can drive the dynamics of a two-electron Wigner molecule held in a square quantum dot. We find that, for certain combinations of frequency and strength of the applied field, the tunneling between various charge configurations can be strongly quenched, and we relate this phenomenon to the presence of anti-crossings in the Floquet quasi-energy spectrum. We further obtain simple analytic expressions for the location of these anti-crossings, which allows the effective parameters for a given quantum dot to be directly measured in experiment, and suggests the exciting possibility of using ac-fields to control the time evolution of entangled states in mesoscopic devices.Comment: Replaced with version to be published in Phys. Rev.

Delegation of Obligations and Responsibility

Part 6: Policy Compliance and ObligationsInternational audienceIn this paper, we discuss the issue of responsibilities related to the fulfillment and the violation of obligations. We propose to formally define the different aspects of responsibility, namely causal responsibility, functional responsibility, liability as well as sanctions, and to examine how delegation influences these concepts. Our main aim is to identify the responsibility of each agent that is involved in the delegation of obligations. More precisely, we try to answer to the following questions: who is responsible for the obligation fulfillment? When a violation occurs, which agents are causally responsible for this violation? Who is liable for this violation and to whom? And finally, who must be sanctioned

What fraction of stars formed in infrared galaxies at high redshift?

Star formation happens in two types of environment: ultraviolet-bright starbursts (like 30 Doradus and HII galaxies at low redshift and Lyman-break galaxies at high redshift) and infrared-bright dust-enshrouded regions (which may be moderately star-forming like Orion in the Galaxy or extreme like the core of Arp 220). In this work I will estimate how many of the stars in the local Universe formed in each type of environment, using observations of star-forming galaxies at all redshifts at different wavelengths and of the evolution of the field galaxy population.Comment: 7 pages, 0 figs, to appear in proceedings of "Starbursts - From 30 Doradus to Lyman break galaxies", edited by Richard de Grijs and Rosa M. Gonzalez Delgado, published by Kluwe

Au+Au Reactions at the AGS: Experiments E866 and E917

Particle production and correlation functions from Au+Au reactions have been measured as a function of both beam energy (2-10.7AGeV) and impact parameter. These results are used to probe the dynamics of heavy-ion reactions, confront hadronic models over a wide range of conditions and to search for the onset of new phenomena.Comment: 12 pages, 14 figures, Talk presented at Quark Matter '9

Exceptions for Algorithmic Skeletons

to appearInternational audienceAlgorithmic Skeletons offer high-level abstractions for parallel programming based on recurrent parallelism patterns. Patterns can be combined and nested into more complex parallelism behaviors. Programmers fill the skeleton patterns with the functional (business) code, which transforms the generic skeleton into a specific application. However, when the functional code generate exceptions, this exposes the programmer to details of the skeleton library, breaking the high-level abstraction principle. Furthermore, related parallel activities must be stopped as the exception is raised. This paper describes how to handle exceptions in Algorithmic Skeletons without breaking the high-level abstractions of the programming model. We describe both the behavior of the framework in a formal way, and its implementation in Java: the Skandium Library

Young and Intermediate-age Distance Indicators

Distance measurements beyond geometrical and semi-geometrical methods, rely mainly on standard candles. As the name suggests, these objects have known luminosities by virtue of their intrinsic proprieties and play a major role in our understanding of modern cosmology. The main caveats associated with standard candles are their absolute calibration, contamination of the sample from other sources and systematic uncertainties. The absolute calibration mainly depends on their chemical composition and age. To understand the impact of these effects on the distance scale, it is essential to develop methods based on different sample of standard candles. Here we review the fundamental properties of young and intermediate-age distance indicators such as Cepheids, Mira variables and Red Clump stars and the recent developments in their application as distance indicators.Comment: Review article, 63 pages (28 figures), Accepted for publication in Space Science Reviews (Chapter 3 of a special collection resulting from the May 2016 ISSI-BJ workshop on Astronomical Distance Determination in the Space Age

Horizontal Branch Stars: The Interplay between Observations and Theory, and Insights into the Formation of the Galaxy

We review HB stars in a broad astrophysical context, including both variable and non-variable stars. A reassessment of the Oosterhoff dichotomy is presented, which provides unprecedented detail regarding its origin and systematics. We show that the Oosterhoff dichotomy and the distribution of globular clusters (GCs) in the HB morphology-metallicity plane both exclude, with high statistical significance, the possibility that the Galactic halo may have formed from the accretion of dwarf galaxies resembling present-day Milky Way satellites such as Fornax, Sagittarius, and the LMC. A rediscussion of the second-parameter problem is presented. A technique is proposed to estimate the HB types of extragalactic GCs on the basis of integrated far-UV photometry. The relationship between the absolute V magnitude of the HB at the RR Lyrae level and metallicity, as obtained on the basis of trigonometric parallax measurements for the star RR Lyrae, is also revisited, giving a distance modulus to the LMC of (m-M)_0 = 18.44+/-0.11. RR Lyrae period change rates are studied. Finally, the conductive opacities used in evolutionary calculations of low-mass stars are investigated. [ABRIDGED]Comment: 56 pages, 22 figures. Invited review, to appear in Astrophysics and Space Scienc

Fitting the integrated Spectral Energy Distributions of Galaxies

Fitting the spectral energy distributions (SEDs) of galaxies is an almost universally used technique that has matured significantly in the last decade. Model predictions and fitting procedures have improved significantly over this time, attempting to keep up with the vastly increased volume and quality of available data. We review here the field of SED fitting, describing the modelling of ultraviolet to infrared galaxy SEDs, the creation of multiwavelength data sets, and the methods used to fit model SEDs to observed galaxy data sets. We touch upon the achievements and challenges in the major ingredients of SED fitting, with a special emphasis on describing the interplay between the quality of the available data, the quality of the available models, and the best fitting technique to use in order to obtain a realistic measurement as well as realistic uncertainties. We conclude that SED fitting can be used effectively to derive a range of physical properties of galaxies, such as redshift, stellar masses, star formation rates, dust masses, and metallicities, with care taken not to over-interpret the available data. Yet there still exist many issues such as estimating the age of the oldest stars in a galaxy, finer details ofdust properties and dust-star geometry, and the influences of poorly understood, luminous stellar types and phases. The challenge for the coming years will be to improve both the models and the observational data sets to resolve these uncertainties. The present review will be made available on an interactive, moderated web page (sedfitting.org), where the community can access and change the text. The intention is to expand the text and keep it up to date over the coming years.Comment: 54 pages, 26 figures, Accepted for publication in Astrophysics & Space Scienc