Redistribution of critical major histocompatibility complex and T cell receptor-binding functions of residues in an antigenic sequence after biterminal substitution

Residues critical for establishing a trimolecular interaction with a major histocompatibility complex (MHC)-encoded receptor and a T cell antigen receptor (TcR) were determined for an antigenic nonapeptide. The N-terminal residue proved to be involved in binding of the peptide to both receptors and the C-terminal residue was essential for MHC binding. While substitution of either of these critical terminal residues by alanine resulted in an almost complete loss of peptide antigenicity, simultaneous substitution of both created a new functional ligand for the same MHC molecule and the same TcR. Notably, in the biterminally substituted peptide, the core residues took on new roles in the trimolecular interaction in that a residue critical in the authentic nonapeptide for TcR binding became critical for MHC binding and former spacer residues became essential to various degrees for the interaction with either receptor or both. Thus, apparently, the loss of the terminal residues' contribution was at least partially compensated by a redistribution of the roles among the remaining residues. These results reflect a cooperative contribution of all residues of an antigenic peptide to its binding to both receptors and thus challenge a static definition of agretope and epitope as MHC and TcR binding sites

First International Conference on Laboratory Research for Planetary Atmospheres

Proceedings of the First International Conference on Laboratory Research for Planetary Atmospheres are presented. The covered areas of research include: photon spectroscopy, chemical kinetics, thermodynamics, and charged particle interactions. This report contains the 12 invited papers, 27 contributed poster papers, and 5 plenary review papers presented at the conference. A list of attendees and a reprint of the Report of the Subgroup on Strategies for Planetary Atmospheres Exploration (SPASE) are provided in two appendices

Contamination in complex healthcare trials:the falls in care homes (FinCH) study experience

BACKGROUND: Trials are at risk of contamination bias which can occur when participants in the control group are inadvertently exposed to the intervention. This is a particular risk in rehabilitation studies where it is easy for trial interventions to be either intentionally or inadvertently adopted in control settings. The Falls in Care Homes (FinCH) trial is used in this paper as an example of a large randomised controlled trial of a complex intervention to explore the potential risks of contamination bias. We outline the FinCH trial design, present the potential risks from contamination bias, and the strategies used in the design of the trial to minimise or mitigate against this. The FinCH trial was a multi-centre randomised controlled trial, with embedded process evaluation, which evaluated whether systematic training in the use of the Guide to Action Tool for Care Homes reduced falls in care home residents. Data were collected from a number of sources to explore contamination in the FinCH trial. Where specific procedures were adopted to reduce risk of, or mitigate against, contamination, this was recorded. Data were collected from study e-mails, meetings with clinicians, research assistant and clinician network communications, and an embedded process evaluation in six intervention care homes. During the FinCH trial, there were six new falls prevention initiatives implemented outside the study which could have contaminated our intervention and findings. Methods used to minimise contamination were: cluster randomisation at the level of care home; engagement with the clinical community to highlight the risks of early adoption; establishing local collaborators in each site familiar with the local context; signing agreements with NHS falls specialists that they would maintain confidentiality regarding details of the intervention; opening additional research sites; and by raising awareness about the importance of contamination in research among participants. CONCLUSION: Complex rehabilitation trials are at risk of contamination bias. The potential for contamination bias in studies can be minimized by strengthening collaboration and dialogue with the clinical community. Researchers should recognise that clinicians may contaminate a study through lack of research expertise

A case study of colliding tornadic storms

Abstract only availableTornadoes occur frequently across the United States each year, causing millions of dollars in damage. Meteorologists are constantly searching for new and improved methods for predicting these weather phenomenons's in order to increase public awareness and warning times. In this case study, one event was found in which two storm cells collided and produced a tornado over the Kansas City, Missouri area, causing an extensive amount of damage. The goals of this study is to first determine what caused the collision between the two storm cells, secondly, whether the collision between the two storm cells increased the intensity of the tornado using NSSL/SPC (National Severe Storms Laboratory/ Storm Prediction Center) meteorologist Stephen F. Corfidi's “vector approach.” A method that involves the use of mathematics to find the mean of the wind directions throughout the cloud layers in the storms and also the location of the low-level jet. Radar imagery was also used in determining the location, time, intensity, and other details of the two storm cells. It is our hope, that the completion of this study will produce results that are conducive to the development of more innovative methods for forecasting this type of event.Louis Stokes Alliance for Minority Participatio

Health, ethics and environment: A qualitative study of vegetarian motivations

This qualitative study explored the motivations of vegetarians by means of online ethnographic research with participants in an international message board. The researcher participated in discussions on the board, gathered responses to questions from 33 participants, and conducted follow-up e-mail interviews with eighteen of these participants. Respondents were predominantly from the US, Canada and the UK. Seventy per cent were female, and ages ranged from 14 to 53, with a median of 26 years. Data were analysed using a thematic approach. While this research found that health and the ethical treatment of animals were the main motivators for participants’ vegetarianism, participants reported a range of commitments to environmental concerns, although in only one case was environmentalism a primary motivator for becoming a vegetarian. The data indicates that vegetarians may follow a trajectory, in which initial motivations are augmented over time by other reasons for sustaining or further restricting their diet

Web 2.0 and folksonomies in a library context

This is the post-print version of the Article. The official published version can be accessed from the link below - Copyright @ 2011 ElsevierLibraries have a societal purpose and this role has become increasingly important as new technologies enable organizations to support, enable and enhance the participation of users in assuming an active role in the creation and communication of information. Folksonomies, a Web 2.0 technology, represent such an example. Folksonomies result from individuals freely tagging resources available to them on a computer network. In a library environment folksonomies have the potential of overcoming certain limitations of traditional classification systems such as the Library of Congress Subject Headings (LCSH). Typical limitations of this type of classification systems include, for example, the rigidity of the underlying taxonomical structures and the difficulty of introducing change in the categories. Folksonomies represent a supporting technology to existing classification systems helping to describe library resources more flexibly, dynamically and openly. As a review of the current literature shows, the adoption of folksonomies in libraries is novel and limited research has been carried out in the area. This paper presents research into the adoption of folksonomies for a University library. A Web 2.0 system was developed, based on the requirements collected from library stakeholders, and integrated with the existing library computer system. An evaluation of the work was carried out in the form of a survey in order to understand the possible reactions of users to folksonomies as well as the effects on their behavior. The broad conclusion of this work is that folksonomies seem to have a beneficial effect on users’ involvement as active library participants as well as encourage users to browse the catalogue in more depth

Faster Algorithms for the Geometric Transportation Problem

Let R, B be a set of n points in R^d, for constant d, where the points of R have integer supplies, points of B have integer demands, and the sum of supply is equal to the sum of demand. Let d(.,.) be a suitable distance function such as the L_p distance. The transportation problem asks to find a map tau : R x B --> N such that sum_{b in B}tau(r,b) = supply(r), sum_{r in R}tau(r,b) = demand(b), and sum_{r in R, b in B} tau(r,b) d(r,b) is minimized. We present three new results for the transportation problem when d(.,.) is any L_p metric: * For any constant epsilon > 0, an O(n^{1+epsilon}) expected time randomized algorithm that returns a transportation map with expected cost O(log^2(1/epsilon)) times the optimal cost. * For any epsilon > 0, a (1+epsilon)-approximation in O(n^{3/2}epsilon^{-d}polylog(U)polylog(n)) time, where U is the maximum supply or demand of any point. * An exact strongly polynomial O(n^2 polylog n) time algorithm, for d = 2

Characterizing Transition Temperature Gas in the Galactic Corona

We present a study of the properties of the transition temperature (T~10^5 K) gas in the Milky Way corona, based on measurements of OVI, NV, CIV, SiIV and FeIII absorption lines seen in the far ultraviolet spectra of 58 sightlines to extragalactic targets, obtained with Far-Ultraviolet Spectroscopic Explorer (FUSE) and Space Telescope Imaging Spectrograph. In many sightlines the Galactic absorption profiles show multiple components, which are analyzed separately. We find that the highly-ionized atoms are distributed irregularly in a layer with a scaleheight of about 3 kpc, which rotates along with the gas in the disk, without an obvious gradient in the rotation velocity away from the Galactic plane. Within this layer the gas has randomly oriented velocities with a dispersion of 40-60 km/s. On average the integrated column densities are log N(OVI)=14.3, log N(NV)=13.5, log N(CIV)=14.2, log N(SiIV)=13.6 and log N(FeIII)=14.2, with a dispersion of just 0.2 dex in each case. In sightlines around the Galactic Center and Galactic North Pole all column densities are enhanced by a factor ~2, while at intermediate latitudes in the southern sky there is a deficit in N(OVI) of about a factor 2, but no deficit for the other ions. We compare the column densities and ionic ratios to a series of theoretical predictions: collisional ionization equilibrium, shock ionization, conductive interfaces, turbulent mixing, thick disk supernovae, static non-equilibrium ionization (NIE) radiative cooling and an NIE radiative cooling model in which the gas flows through the cooling zone. None of these models can fully reproduce the data, but it is clear that non-equilibrium ionization radiative cooling is important in generating the transition temperature gas.Comment: 99 pages, 11 figures, with appendix on Cooling Flow model; only a sample of 5 subfigures of figure 2 included - full set of 69 available through Ap

A formal verification framework and associated tools for enterprise modeling : application to UEML

The aim of this paper is to propose and apply a verification and validation approach to Enterprise Modeling that enables the user to improve the relevance and correctness, the suitability and coherence of a model by using properties specification and formal proof of properties