Direct observation of disordered regions in the major histocompatibility complex class II-associated invariant chain.

Invariant chain (Ii) is a trimeric membrane protein which binds and stabilizes major histocompatibility complex class II heterodimers in the endoplasmic reticulum and lysosomal compartments of antigen-presenting cells. In concert with an intracellular class II-like molecule, HLA-DM, Ii seems to facilitate loading of conventional class II molecules with peptides before transport of the class II-peptide complex to the cell surface for recognition by T cells. The interaction of Ii with class II molecules is thought to be mediated in large part through a region of 24 amino acids (the class II-associated Ii peptide, CLIP) which binds as a cleaved moiety in the antigenic peptide-binding groove of class II molecules in HLA-DM-deficient cell lines. Here we use nuclear magnetic resonance techniques to demonstrate that a soluble recombinant Ii ectodomain contains significant disordered regions which probably include CLIP.

A general model of invariant chain association with class II major histocompatibility complex proteins.

The binding of invariant chain to major histocompatibility complex (MHC) proteins is an important step in processing of MHC class II proteins and in antigen presentation. The question of how invariant chain can bind to all MHC class II proteins is central to understanding these processes. We have employed molecular modeling to predict the structure of class II-associated invariant chain peptide (CLIP)-MHC protein complexes and to ask whether the predicted mode of association could be general across all MHC class II proteins. CLIP fits identically into the MHC class II alleles HLA-DR3, I-Ak, I-Au, and I-Ad, with a consistent pattern of hydrogen bonds, contacts, and hydrophobic burial and without bad contacts. Our model predicts the burial of CLIP residues Met-91 and Met-99 in the deep P1 and P9 anchor pockets and other detailed interactions, which we have compared with available data. The predicted pattern of I-A allele-specific effects on CLIP binding is very similar to that observed experimentally by alanine-scanning mutations of CLIP. Together, these results indicate that CLIP may bind in a single, general way across products of MHC class II alleles.

Structural features of the invariant chain fragment CLIP controlling rapid release from HLA-DR molecules and inhibition of peptide binding.

The invariant chain (Ii) prevents binding of ligands to major histocompatibility complex (MHC) class II molecules in the endoplasmic reticulum and during intracellular transport. Stepwise removal of the Ii in a trans-Golgi compartment renders MHC class II molecules accessible for peptide loading, with CLIP (class II-associated Ii peptides) as the final fragment to be released. Here we show that CLIP can be subdivided into distinct functional regions. The C-terminal segment (residues 92-105) of the CLIP-(81-105) fragment mediates inhibition of self- and antigenic peptide binding to HLA-DR2 molecules. In contrast, the N-terminal segment CLIP-(81-98) binds to the Staphylococcus aureus enterotoxin B contact site outside the peptide-binding groove on the alpha 1 domain and does not interfere with peptide binding. Its functional significance appears to lie in the contribution to CLIP removal: the dissociation of CLIP-(81-105) is characterized by a fast off-rate, which is accelerated at endosomal pH, whereas in the absence of the N-terminal CLIP-(81-91), the off-rate of C-terminal CLIP-(92-105) is slow and remains unaltered at low pH. Mechanistically, the N-terminal segment of CLIP seems to prevent tight interactions of CLIP side chains with specificity pockets in the peptide-binding groove that normally occurs during maturation of long-lived class II-peptide complexes.

Expression of endogenous peptide-major histocompatibility complex class II complexes derived from invariant chain-antigen fusion proteins.

CD4+ T cells recognize major histocompatibility complex (MHC) class II-bound peptides that are primarily obtained from extracellular sources. Endogenously synthesized proteins that readily enter the MHC class I presentation pathway are generally excluded from the MHC class II presentation pathway. We show here that endogenously synthesized ovalbumin or hen egg lysozyme can be efficiently presented as peptide-MHC class II complexes when they are expressed as fusion proteins with the invariant chain (Ii). Similar to the wild-type Ii, the Ii-antigen fusion proteins were associated intracellularly with MHC molecules. Most efficient expression of endogenous peptide-MHC complex was obtained with fusion proteins that contained the endosomal targeting signal within the N-terminal cytoplasmic Ii residues but did not require the luminal residues of Ii that are known to bind MHC molecules. These results suggest that signals within the Ii can allow endogenously synthesized proteins to efficiently enter the MHC class II presentation pathway. They also suggest a strategy for identifying unknown antigens presented by MHC class II molecules.

The deferred imitation task as a nonverbal measure of declarative memory.

We tested amnesic patients, patients with frontal lobe lesions, and control subjects with the deferred imitation task, a nonverbal test used to demonstrate memory abilities in human infants. On day 1, subjects were given sets of objects to obtain a baseline measure of their spontaneous performance of target actions. Then different event sequences were modeled with the object sets. On day 2, the objects were given to the subjects again, first without any instructions to imitate the sequences, and then with explicit instructions to imitate the actions exactly as they had been modeled. Control subjects and frontal lobe patients reproduced the events under both uninstructed and instructed conditions. In contrast, performance by the amnesic patients did not significantly differ from that of a second control group who had the same opportunities to handle the objects but were not shown the modeled actions. These findings suggest that deferred imitation is dependent on the brain structures essential for declarative memory that are damaged in amnesia, and they support the view that infants who imitate actions after long delays have an early capacity for long-term declarative memory.

Analytical method to measure bending deformations in prismatic optical films

The aim of this work is to provide an analytical method based on experimental measurements in order to obtain the prismatic film deformation for different curvatures of Hollow Cylindrical Prismatic Light Guides (CPLG). To conform cylindrical guides is necessary bend the film to guide the light, changes induced by curving the film give rise to deformation shifts. Light losses affected by deformation has been experimentally evaluated and numerically analyzed. The effect of deformation in prism angle is specially increased for CPLG of curvatures higher than 20 m-1. An experimental method for accurate transmittance measurements related to bending is presented.

A new modularity measure for Fuzzy Community detection problems based on overlap and grouping functions

One of the main challenges of fuzzy community detection problems is to be able to measure the quality of a fuzzy partition. In this paper, we present an alternative way of measuring the quality of a fuzzy community detection output based on n-dimensional grouping and overlap functions. Moreover, the proposed modularity measure generalizes the classical Girvan–Newman (GN) modularity for crisp community detection problems and also for crisp overlapping community detection problems. Therefore, it can be used to compare partitions of different nature (i.e. those composed of classical, overlapping and fuzzy communities). Particularly, as is usually done with the GN modularity, the proposed measure may be used to identify the optimal number of communities to be obtained by any network clustering algorithm in a given network. We illustrate this usage by adapting in this way a well-known algorithm for fuzzy community detection problems, extending it to also deal with overlapping community detection problems and produce a ranking of the overlapping nodes. Some computational experiments show the feasibility of the proposed approach to modularity measures through n-dimensional overlap and grouping functions.

Development of a psychological assessment battery to measure client beliefs about the effectiveness of psychotherapy

The author attempted to develop a brief scale to measure clients' beliefs about the effectiveness of psychotherapy. The study is an early pilot study to determine if the scale can predict therapy outcomes. While the scale did differ significantly between clients who were active in therapy and those who were not, higher scores on the instrument were not indicative of greater involvement. Possibilities for future research to refine the instrument are discussed.

Development of the DORI-TBI: An Investigation to Develop a New Screening Measure to Determine Consultation with a School-Based Brain Injury Resource Team

Brain injury is the leading cause of disability and death in children in the United States. Student re-entry into the school setting following a traumatic brain injury is crucial to student success. Multidisciplinary teams within the school district comprised of individuals with expertise in brain injury are ideal in implementing student specific treatment plans given their specialized training and wide range of expertise addressing student needs. Therefore, the purpose of this study is to develop and initially validate a quantitative instrument that school personnel can use to determine if a student, identified as having a traumatic brain injury, will benefit from district-level consultation from a brain injury team. Three studies were designed to investigate the research questions. In study one, the planning and construction of the DORI-TBI was completed. Study two addressed the content validity of the DORI-TBI through a comparison analysis with other referral forms, content review with experts in the field of TBI, and cognitive interviews with professionals to test the usability of the new screening tool. In study three, a field administration was conducted using vignettes to measure construct validity. Results produced a valid and reliable new screening instrument that can aid school-based teams to more efficiently utilize district level consultation with a brain injury support team.

Psychometric Investigation of the Check-In, Check-Out Fidelity of Implementation Measure

Suspension and expulsion are utilized frequently and disproportionality in schools in the United States. Many schools utilize Positive Behavioral Interventions and Supports (PBIS), a tiered framework to prevent problem behavior and reduce the use of discipline practices (Sugai et al., 2000). Check-In, Check-Out (CICO) is a targeted group behavioral intervention that is utilized within this framework in schools to prevent severe problem behavior in students that are beginning to exhibit externalizing and/or internalizing behavioral needs; thus, preventing the use of exclusionary discipline practices (Crone et al., 2010; Hawken & Horner, 2003). As the use of CICO in schools continues to grow, so too does the need for an instrument measuring its fidelity of implementation. The purpose of this study was to investigate the reliability and validity of the Check-In, Check-Out Fidelity of Implementation Measure (Crone et al., 2010), an instrument created to measure the fidelity of implementation of CICO intervention. This study assessed the psychometric properties of the instrument utilizing an archival data set collected by the statewide PBIS initiative in a western state in the U.S. The results demonstrated promising content validity, construct validity, internal consistency, and interrater reliability. A unidimensional structure was determined to be the best structure for the instrument based on parsimony and the strong results obtained from the item loadings, internal consistency, and interrater reliability. Implications for use and future research are discussed.

Measure of Maturity: The Montana Adolescent Maturity Assessment

The construct of maturity is often discussed in the realm of adolescent development; however, relatively little research has been devoted to developing a comprehensive, reliable, and valid measure with which to assess it. The purpose of this study was to investigate the concurrent validity of the Montana Adolescent Maturity Assessment - III (MAMA-III), a proxy measure completed by clinicians regarding an adolescent's functioning, with the immaturity scale (IMM) of the MMPI-A. To provide more specified results, a factor analysis of the IMM was undertaken. Results yielded a low but significant correlation between the MAMA-III and the IMM, as well as significant convergent correlations between individual factors of the MAMA and IMM scales. Correlations among the MAMA-III factors, the IMM factors, and the ten clinical scales of the MMPI-A were also analyzed with the goal of better understanding what each measures. Implications are discussed regarding the clinical distinctions between the two measures, and the prospect of a more comprehensive understanding of the construct of maturity.

Planning for the Future: Gray Water Supply as a Conservation Measure for a Key Water Provider in Douglas County, Colorado

Diminishing water in the Denver Basin aquifers requires Parker Water and Sanitation District plan for the future to ensure availability of supply. Water conservation is one approach to prolonging the life of the aquifers. Homeowner installed gray water systems will help conserve 25 percent of the water needed and reduce the need to pump ground water for irrigation. Non-potable water through gray water systems will reduce the demand on the supplier. Gray water use will prolong a potable supply to Parker for years ahead. For this plan to be effective, Colorado regulations must change to allow gray water use. This goal will be achieved as the mind-set about water conservation shifts and water suppliers and consumers demand modification to policies.

Use of subpixel techniques in pocket cameras to measure vibrations and displacements

Presentación oral SPIE Photonics Europe, Brussels, 16-19 April 2012.

A new betweenness centrality measure based on an algorithm for ranking the nodes of a network

We propose and discuss a new centrality index for urban street patterns represented as networks in geographical space. This centrality measure, that we call ranking-betweenness centrality, combines the idea behind the random-walk betweenness centrality measure and the idea of ranking the nodes of a network produced by an adapted PageRank algorithm. We initially use a PageRank algorithm in which we are able to transform some information of the network that we want to analyze into numerical values. Numerical values summarizing the information are associated to each of the nodes by means of a data matrix. After running the adapted PageRank algorithm, a ranking of the nodes is obtained, according to their importance in the network. This classification is the starting point for applying an algorithm based on the random-walk betweenness centrality. A detailed example of a real urban street network is discussed in order to understand the process to evaluate the ranking-betweenness centrality proposed, performing some comparisons with other classical centrality measures.

Diversity for Texts Builds in Language L(MT): Indexes Based in Theory of Information

If one has a distribution of words (SLUNs or CLUNS) in a text written in language L(MT), and is adjusted one of the mathematical expressions of distribution that exists in the mathematical literature, some parameter of the elected expression it can be considered as a measure of the diversity. But because the adjustment is not always perfect as usual measure; it is preferable to select an index that doesn't postulate a regularity of distribution expressible for a simple formula. The problem can be approachable statistically, without having special interest for the organization of the text. It can serve as index any monotonous function that has a minimum value when all their elements belong to the same class, that is to say, all the individuals belong to oneself symbol, and a maximum value when each element belongs to a different class, that is to say, each individual is of a different symbol. It should also gather certain conditions like they are: to be not very sensitive to the extension of the text and being invariant to certain number of operations of selection in the text. These operations can be theoretically random. The expressions that offer more advantages are those coming from the theory of the information of Shannon-Weaver. Based on them, the authors develop a theoretical study for indexes of diversity to be applied in texts built in modeling language L(MT), although anything impedes that they can be applied to texts written in natural languages.