Determination of a predictive cleavage motif for eluted major histocompatibility complex class II ligands

CD4+ T cells have a major role in regulating immune responses. They are activated by recognition of peptides mostly generated from exogenous antigens through the major histocompatibility complex (MHC) class II pathway. Identification of epitopes is important and computational prediction of epitopes is used widely to save time and resources. Although there are algorithms to predict binding affinity of peptides to MHC II molecules, no accurate methods exist to predict which ligands are generated as a result of natural antigen processing. We utilized a dataset of around 14,000 naturally processed ligands identified by mass spectrometry of peptides eluted from MHC class II expressing cells to investigate the existence of sequence signatures potentially related to the cleavage mechanisms that liberate the presented peptides from their source antigens. This analysis revealed preferred amino acids surrounding both N- and C-terminuses of ligands, indicating sequence-specific cleavage preferences. We used these cleavage motifs to develop a method for predicting naturally processed MHC II ligands, and validated that it had predictive power to identify ligands from independent studies. We further confirmed that prediction of ligands based on cleavage motifs could be combined with predictions of MHC binding, and that the combined prediction had superior performance. However, when attempting to predict CD4+ T cell epitopes, either alone or in combination with MHC binding predictions, predictions based on the cleavage motifs did not show predictive power. Given that peptides identified as epitopes based on CD4+ T cell reactivity typically do not have well-defined termini, it is possible that motifs are present but outside of the mapped epitope. Our attempts to take that into account computationally did not show any sign of an increased presence of cleavage motifs around well-characterized CD4+ T cell epitopes. While it is possible that our attempts to translate the cleavage motifs in MHC II ligand elution data into T cell epitope predictions were suboptimal, other possible explanations are that the cleavage signal is too diluted to be detected, or that elution data are enriched for ligands generated through an antigen processing and presentation pathway that is less frequently utilized for T cell epitopes.Fil: Paul, Sinu. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Karosiene, Edita. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Dhanda, Sandeep Kumar. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Jurtz, Vanessa. Technical University of Denmark; DinamarcaFil: Edwards, Lindy. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Nielsen, Morten. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Investigaciones Biotecnológicas. Universidad Nacional de San Martín. Instituto de Investigaciones Biotecnológicas; Argentina. Technical University of Denmark; DinamarcaFil: Sette, Alessandro. University of California at San Diego; Estados Unidos. La Jolla Institute for Allergy and Immunology; Estados UnidosFil: Peters, Bjoern. La Jolla Institute for Allergy and Immunology; Estados Unidos. University of California at San Diego; Estados Unido

Flexible and Affordable Foreign Language Learning Environment based on Web 2.0 Technologies

Web technologies and educational platforms have greatly evolved over the past decade. One of the most significant factors contributing to education on the Internet has been the development of Web 2.0 technologies. These technologies, socially interactive in nature, have much to contribute to the area of Computer Assisted Language Leaning. Unfortunately, Web 2.0 technologies for the most part have been used in an ad hoc manner, permitting language learners acquire knowledge through interaction, but not through a more structured manner as these technologies were not developed to help lean languages as such. The goal of our work is to research and develop an environment, which employs Web 2.0 technology plus online language learning tools to provide a more integrated language learning environment. This paper will explore the technologies and provide information about how tools can be better integrated to provide a more productive working environment for language learners. A first working proof of concept based on our approach introduced is promising supporting modern language requirements and first findings and space for improvements are discussed

The RUMERTIME Process as a Protective Factor in School Attendance Problems

The RUMERTIME Process (RP) is a five-step culturally responsive social-emotional, problem-solving, prevention-intervention strategy used to educate, equip, and empower students, educators, and families. The RP equips individuals with the abilities to recognize, understand, manage, express, and reflect on their thoughts, interactions, mindsets, and emotions (RUMERTIME) in relation to themselves, others, and the daily life challenges they face within multiple systems and settings. The RP is embedded within the Cultivating SEEDS System framework (CSS) and is utilized to equip culturally diverse communities, inclusive of students, family members, educators, and administrators, with the social-emotional skills to effectively solve student attendance problems (SAPs). The data shared in this practice intervention article are descriptive in nature and highlight the RP as a protective factor and explain its three goals. The paper consists of three parts: (a) introduction of the RP, which is embedded in the CSS framework; (b) description of implementation of the RP as integral to the Daytime Intervention Room (DIR) program; and (c) discussion of risk factors that qualified students to receive services through the DIR program as well as data that demonstrated how the RP performed as a protective factor. The DIR program was aimed at creating an alternative to out-of-school suspension (OSS) and the traditional punitive in-school suspension (ISS). The program was established in each of the four schools in an urban high-needs school district in the midwest region of the United States. The DIR program was intentionally designed to include multiple levels, stakeholders, and delivery support, thus creating a solid base for the holistic development of students, educators, and parents. In conjunction with the CSS framework, the DIR program sought to increase academic performance, decrease the number of behavior referrals, and improve attendance rates in this high-needs urban school district

The development of student learning and information literacy: a case study

Literacy is a fundamental human right. When exercised it improves an individual’s life chances by achieving their personal, social, occupational and educational goals, and opening opportunities for social, economic and political integration. In an information and knowledge society, there is a salient need for Information Literacy (IL). IL can be defined as knowing when and why one might need information, where to find it, and how to evaluate, use and communicate it in an ethical manner. There is a need for undergraduate and postgraduate students to demonstrate a competency with IL skills. For example it is essential for the student to develop a thesis statement and to consequently search, organise, share and evaluate the results. In this paper we present a case study highlighting the role of Library and Student Support (LSS) based at Middlesex University London. LSS works in conjunction with University Departments and leads on the development and implementation of a coherent and strategic approach to improving learner competencies. These are identified through the development and implementation of relevant University policies and strategies. We argue that other Higher Education institutions may benefit from our experience of implementing IL policy in collaboration with a Library and Student Support service