PET Tracers to Study Clinically Relevant Hepatic Transporters

Date of Acceptance: 02/06/2015

GPIIIa-(49–66) is a major pathophysiologically relevant antigenic determinant for anti-platelet GPIIIa of HIV-1-related immunologic thrombocytopenia

High-affinity (Kd = 1 × 10−9 M) anti-platelet GPIIIa has been isolated from serum immune complexes of immunologic thrombocytopenic HIV-1-infected patients (HIV-1-ITP). Affinity-purified anti-platelet antibody reacted with a recombinant GPIIIa-(1–200) and -(1–66) fusion peptide and with an 18-mer GPIIIa-(49–66) peptide but not with seven other GPIIIa peptides spanning the length of GPIIIa. Most of the anti-platelet antibody (≈85%) could be adsorbed to and eluted from a GPIIIa-(49–66) affinity column. Binding of antibody to platelets could be inhibited by GPIIIa-(49–66) or an equimolar peptide-albumin conjugate (IC50 = 2 μM). Sera from 7 control subjects and 10 classic autoimmune thrombocytopenic patients gave background reactivity with GPIIIa-(49–66). HIV-1-ITP sera from 16 patients reacted with a mean OD 6-fold greater than background (range, 4- to 9-fold). Serum anti-GPIIIa-(49–66) concentration correlated inversely with platelet count, R2 = 0.51, n = 31, P < 0.0001. Because mouse platelet GPIIIa-(49–66) has 83% homology with human GPIIIa and mouse monocytes contain Fc receptors for the human IgG1-κ/λ antibody, we determined the in vivo effect of human anti-GPIIIa on mouse platelets. Affinity-purified antibody, 25–50 μg given i.p., resulted in a precipitous drop in platelet count to 30% of baseline, with nadir at 4 hr and return to normal in 36 hr. No effect was noted with control IgG. Acute thrombocytopenia could be prevented or reversed by the injection of the GPIIIa-(49–66) albumin conjugate at zero time or 2 hr after antibody, respectively, but not with a scrambled peptide-albumin conjugate. Thus HIV-1-ITP patients have high-affinity anti-platelet GPIIIa against a major antigenic determinant, GPIIIa-(49–66), which correlates inversely with platelet count and induces thrombocytopenia in mice.

An in vitro study of the dynamic features of the major histocompatibility complex class I complex relevant to its role as a versatile peptide-receptive molecule

The major histocompatibility complex class I complex consists of a heavy chain and a light chain (β2-microglobulin, β2m), which assemble with a short endogenously derived peptide in the endoplasmic reticulum. The class I peptide can be directly exchanged, either at the cell surface or, as recently described, in vesicles of the endocytic compartments, thus allowing exogenous peptides to enter the class I presentation pathway. To probe the interactions between the components of the class I molecule, we analyzed the exchange of peptide and β2m by using purified, recombinant H2-Kb/peptide complexes in a cell-free in vitro system. The exchange of competitor peptide was primarily dependent on the off-rate of the original peptide in the class I binding groove. Peptide exchange was not enhanced by the presence of exogenous β2m, as exchange occurred to the same extent in its absence. Thus, the exchange of peptide and β2m are independent events. The exchange rate of β2m also was not affected by the dissociation rates of the original peptides. Furthermore, peptides could substantially exchange into class I molecules over a pH range of 5.5 to 7.5, conditions prevalent in certain endocytic compartments. We conclude that the dynamic properties of the components of class I molecules explain its function as a highly peptide-receptive molecule. The major histocompatibility complex class I can readily receive peptides independent of the presence of exogenous β2m, even at a low pH. Such properties are relevant to class I peptide acquisition, which can occur at the cell surface, as well as in specialized endosomes.

A two-year experience teaching computer literacy to first-year medical students using skill-based cohorts

Because it is widely accepted that providing information online will play a major role in both the teaching and practice of medicine in the near future, a short formal course of instruction in computer skills was proposed for the incoming class of students entering medical school at the State University of New York at Stony Brook. The syllabus was developed on the basis of a set of expected outcomes, which was accepted by the dean of medicine and the curriculum committee for classes beginning in the fall of 1997. Prior to their arrival, students were asked to complete a self-assessment survey designed to elucidate their initial skill base; the returned surveys showed students to have computer skills ranging from complete novice to that of a systems engineer. The classes were taught during the first three weeks of the semester to groups of students separated on the basis of their knowledge of and comfort with computers. Areas covered included computer basics, e-mail management, MEDLINE, and Internet search tools. Each student received seven hours of hands-on training followed by a test. The syllabus and emphasis of the classes were tailored to the initial skill base but the final test was given at the same level to all students. Student participation, test scores, and course evaluations indicated that this noncredit program was successful in achieving an acceptable level of comfort in using a computer for almost all of the student body.

"i Went To The Woods Because I Wished To Live Deliberately": How A College-Level Academic Course Can Influence A Lifetime

This study, using the portraiture methodology, provides an analysis of the lifelong significance of an undergraduate program that integrates literature with an outdoor experiential platform. With limited research on long-term effects of an academic outdoor experiential course on one's life, there is space to wonder about the prospect and nature of the long-term significance of an academic course that may offer technical skill, intrapersonal and interpersonal development, and also the delivery of subject matter related to a traditional or mainstream academic area of study. Utilizing an academic skills-oriented lens as well as a character strengths lens, portraits were crafted of four former participants of the University of Michigan's New England Literature Program (NELP) to shed light on the long-term influence of this type of course, crucial participant characteristics that contribute to the program's impact, and specific components of the program that are particularly integral to the course's efficacy. Since 1975, each spring term a small contingent of students and educators has lived in the woods in the New England region as a community of learners, artists and explorers. NELP is an exemplar of a longstanding undergraduate academic English course that integrates the literature of New England writers, exploratory writing and student experiences relating to regional literature and the land. Emergent themes of this course's long-term influence on former participants include increased collaborative skills, increased self-confidence and self-knowledge, a reinforcement of lifelong relationships with the outdoors, and nurtured creativity. For participants to reap benefit from this course, it was important for them to enter with maturity to conduct themselves with openness to new experiences, relationships, and extensive reflection. Findings relating to the integral components of such a program include that of being place-based, oriented towards process, and being an intentional, collaborative community.

Broadening the Scope of Ethnic Identity: A Social Sustainability Solution for Pan African Communities through Ethnically Relevant Educational Programming

This conceptual study explores ethnic identity development theory in order to argue that ethnic identity development education is a means of developing broad senses of community in the African Diaspora that expand beyond a tribal, local, familial level. This study suggests that the broadening of community understanding would contribute to establishing social sustainability on regional, national and international levels within the Pan African community. Establishing such social sustainability would have direct effects on the areas of economic and environmental sustainability. One of the goals of this project is to offer suggestions for ethnically relevant education that can develop social sustainability in several places throughout the Diaspora, such as in Nigeria where ethnic conflicts are a contemporary concern.

Culture Industries in a Postindustrial Age: Entertainment, Leisure, Creativity, Design

This article reviews the evolution of the concept of culture industries, when neither industry nor culture themselves are today what they were at the time when the term was coined. It attempts to explain the dilution of the term into more nebulous terms (“leisure industries,” “entertainment industries” or “creative industries”) and suggests new challenges for the research on culture industries. What is at stake is no longer an application of a Fordist production to culture, a one-directional mass communication and a mediation by experts, but rather: (1) a cultural experience which is no longer clearly separated from other activities (leisure in general, consumption and even work); (2) the communicative explosion of all industrial production in a media environment, where industrialized symbolic products are mixed with culturalized industrial products; and (3) the empowerment of the recipient, which on one hand ignores the traditional experts and on the other leads to post-productive (recreational and even creative) cultural practices.

¿Cómo estudiantes para profesor de matemáticas comprenden el aprendizaje del límite de una función?

En este estudio presentamos una investigación que tiene como objetivo generar información sobre cómo estudiantes para profesor de educación secundaria (EPS) comprenden el proceso de aprendizaje de las matemáticas. El contexto que hemos utilizado es la actividad de anticipar respuestas de los estudiantes de Bachillerato que reflejen diferentes niveles de desarrollo conceptual de la comprensión del concepto de límite de una función, como una actividad relevante vinculada a la competencia docente. Los resultados muestran dos formas distintas de considerar la comprensión del concepto de límite por parte de los EPS que tienen implicación sobre cómo anticipan las respuestas de los estudiantes y sobre las características de los problemas que plantean para apoyar el aprendizaje de la concepción dinámica de límite de los estudiantes.

Gender and health inequalities: intersections with other relevant axes of oppression

The risk of disease, disability, and mortality as well as access to health services are unfairly distributed among the population, with certain groups bearing an unequally larger burden of ill health and poorer access to care due to gender, sexual identity/orientation, ethnic background, or class. According to the WHO Commission on Social Determinants of Health (CSDH), these health inequalities emanate from socioeconomic and political factors (governance, cultural values, macroeconomic policies), which generate a set of socioeconomic positions in society according to which populations are stratified based on gender, ethnicity, education, income, or other factors. These societal inequalities influence people’s material and psychosocial circumstances as well as behavioral and biological factors, which in turn impact on health inequalities. Tackling gender, race/ethnic, and socioeconomic inequalities in society is thus recognized as the most powerful action to cope with unequal health risks distribution, and social innovations focusing on these ‘root causes’ are needed in order to prevent and stop endemic social inequalities and social exclusion in health within low-income as well as high-income countries. Increasing existing knowledge and making visible the health status of the most vulnerable and invisible groups are critical in order to contribute to this imperative challenge.

ISSP Position Stand: To Test or Not to Test? The Use of Physical Skill Tests in Early Phases of Sport Development

A Searching for talent and the assessing ability in young prospects from individual and team sports often include measurement, analysis, and evaluation of physical and motor skills. The use of these tests in early stages of talent development has been widely observed in both female and male prospects. The purpose of this paper is to review a series of studies conducted on talented and less-talented athletes/ players that were aimed at distinguishing between the two groups and at predicting the athletes’/players’ future achievements/success. Thirteen studies examining the use of physical and motor skill tests in young prospects are reviewed. Based on this review, four main observations are highlighted and a number of benefits and limitations associated with the use of such tests are discussed. It is recommended that (1) coaches reduce the number of batteries of physical and motor skill tests used in early phases of talent development and (2) coaches and sport scientists specializing in measurement and evaluation cooperate in order to improve the effectiveness of the application and interpretation of physical skill tests given to prospects at early stages of talent development.

The Contribution of Structured Activity and Deliberate Play to the Development of Expert Perceptual and Decision-Making Skill

The developmental histories of 32 players in the Australian Football League (AFL), independently classified as either expert or less skilled in their perceptual and decision- making skills, were collected through a structured interview process and their year-on-year involvement in structured and deliberate play activities retrospectively determined. Despite being drawn from the same elite level of competition, the expert decision-makers differed from the less skilled in having accrued, during their developing years, more hours of experience in structured activities of all types, in structured activities in invasion-type sports, in invasion-type deliberate play, and in invasion activities from sports other than Australian football. Accumulated hours invested in invasion-type activities differentiated between the groups, suggesting that it is the amount of invasion-type activity that is experienced and not necessarily intent (skill development or fun) or specificity that facilitates the development of perceptual and decision-making expertise in this team sport.