Enhanced cytotoxicity and decreased CD8 dependence of human cancer-specific cytotoxic T lymphocytes after vaccination with low peptide dose.

In mice, vaccination with high peptide doses generates higher frequencies of specific CD8+ T cells, but with lower avidity compared to vaccination with lower peptide doses. To investigate the impact of peptide dose on CD8+ T cell responses in humans, melanoma patients were vaccinated with 0.1 or 0.5 mg Melan-A/MART-1 peptide, mixed with CpG 7909 and Incomplete Freund's adjuvant. Neither the kinetics nor the amplitude of the Melan-A-specific CD8+ T cell responses differed between the two vaccination groups. Also, CD8+ T cell differentiation and cytokine production ex vivo were similar in the two groups. Interestingly, after low peptide dose vaccination, Melan-A-specific CD8+ T cells showed enhanced degranulation upon peptide stimulation, as assessed by CD107a upregulation and perforin release ex vivo. In accordance, CD8+ T cell clones derived from low peptide dose-vaccinated patients showed significantly increased degranulation and stronger cytotoxicity. In parallel, Melan-A-specific CD8+ T cells and clones from low peptide dose-vaccinated patients expressed lower CD8 levels, despite similar or even stronger binding to tetramers. Furthermore, CD8+ T cell clones from low peptide dose-vaccinated patients bound CD8 binding-deficient tetramers more efficiently, suggesting that they may express higher affinity TCRs. We conclude that low peptide dose vaccination generated CD8+ T cell responses with stronger cytotoxicity and lower CD8 dependence.

Convergent Approaches for the Synthesis of the Anti-tumoral Peptide, Kahalalide F. Study of Orthogonal Protecting Groups

Kahalalide compounds are peptides that are isolated from a Hawaiian herbivorous marine species of mollusc, Elysia rufescens, and its diet, the green alga Bryopsis sp. Kahalalide F and its synthetic analogues are the most promising compounds of the Kahalalide family because they show anti-tumoral activity. Linear solid-phase syntheses of Kahalalide F have been reported. Here we describe several new improved synthetic routes based on convergent approaches with distinct orthogonal protection schemes for the preparation of Kahaladide analogues. These strategies allow a better control and characterization of the intermediates because more reactions are performed in solution. Five derivatives of Kahalalide F were synthesized using several convergent approaches.

Dissemination of periodic mammography and patterns of use, by birth cohort, in Catalonia (Spain)

Background: In Catalonia (Spain) breast cancer mortality has declined since the beginning of the 1990s. The dissemination of early detection by mammography and the introduction of adjuvant treatments are among the possible causes of this decrease, and both were almost coincident in time. Thus, understanding how these procedures were incorporated into use in the general population and in women diagnosed with breast cancer is very important for assessing their contribution to the reduction in breast cancer mortality. In this work we have modeled the dissemination of periodic mammography and described repeat mammography behavior in Catalonia from 1975 to 2006. Methods: Cross-sectional data from three Catalan Health Surveys for the calendar years 1994, 2002 and 2006 was used. The dissemination of mammography by birth cohort was modeled using a mixed effects model and repeat mammography behavior was described by age and survey year. Results: For women born from 1938 to 1952, mammography clearly had a period effect, meaning that they started to have periodic mammograms at the same calendar years but at different ages. The age at which approximately 50% of the women were receiving periodic mammograms went from 57.8 years of age for women born in 1938–1942 to 37.3 years of age for women born in 1963–1967. Women in all age groups experienced an increase in periodic mammography use over time, although women in the 50–69 age group have experienced the highest increase. Currently, the target population of the Catalan Breast Cancer Screening Program, 50–69 years of age, is the group that self-reports the highest utilization of periodic mammograms, followed by the 40–49 age group. A higher proportion of women of all age groups have annual mammograms rather than biennial or irregular ones. Conclusion: Mammography in Catalonia became more widely implemented during the 1990s. We estimated when cohorts initiated periodic mammograms and how frequently women are receiving them. These two pieces of information will be entered into a cost-effectiveness model of early detection in Catalonia.

An expression of mixed animal model equations to account for different means and variances in the base population

This paper presents a general expression to predict breeding values using animal models when the base population is selected, i.e. the means and variances of breeding values in the base generation differ among individuals. Rules for forming the mixed model equations are also presented. A numerical example illustrates the procedure.

Los juegos y deportes tradicionales en Europa: entre la tradición y la modernidad

El juego es un elemento básico de socialización: es una creación cultural en el marco de una sociedad determinada. La visión contextualizada de todo juego tradicional debe considerar las propiedades que caracterizan su lógica interna, así como las condiciones socioculturales y los significados simbólicos que le atribuyen sus protagonistas (lógica externa). En esta investigación se realiza un inventario y análisis de la lógica interna y la lógica externa de los juegos tradicionales de adultos que se practican actualmente en 11 regiones europeas. Entre las conclusiones más relevantes destacar que existe un gran repertorio de juegos psicomotores y sociomotores. Se trata de juegos con un alto componente competitivo, en los que se distinguen vencedores y perdedores. Los grupos son básicamente masculinos y mixtos y sin la presencia de un líder o capitán, excepto en las regiones más deportivizadas en las que si aparece esta figura. Se observa que muchas de estas prácticas se están transformando en deportes (regionales), sobre todo aquellas que son protagonizadas por el género masculino. En definitiva, esta investigación aporta datos muy relevantes para comprender la naturaleza de la cultura lúdica tradicional europea.

Els jocs i esports tradicionals a Europa: entre la tradició i la modernitat

El joc és un element bàsic de socialització: és una creació cultural en el marc d’una societat determinada. La visió contextualitzada de qualsevol joc tradicional ha de considerar les propietats que caracteritzen la seva lògica interna, i també les condicions socioculturals i els significats simbòlics que -li atribueixen els seus protagonistes (lògica externa). En aquesta investigació es fa un inventari i una anàlisi de la lògica interna i la lògica externa dels jocs tradicionals d’adults que es practiquen actualment a 11 regions europees. Entre les conclusions més rellevants cal destacar que hi ha un gran repertori de jocs psicomotors i sociomotors. Es tracta de jocs amb un alt component competitiu, en els quals es distingeixen vencedors i perdedors. Els grups són bàsicament masculins i mixtos i sense la presència d’un líder o capità, excepte a les regions més esportivitzades, on sí que apareix aquesta figura. Observem que moltes d’aquestes pràctiques s’estan transformant en esports (regionals), sobretot les que són protagonitzades pel gènere masculí. En resum, aquesta investigació aporta dades molt rellevants per a comprendre la naturalesa de la cultura lúdica tradicional europea.

Assessment of insecticide resistance in eggs and neonate larvae of Cydia pomonella (Lepidoptera: Tortricidae)

Spanish Cydia pomonella (L.) field populations have developed resistance to several insecticide groups. Diagnostic concentrations were established as the LC90 calculated on a susceptible strain (S_Spain) for five and seven insecticides and tested on eggs and neonate larvae field populations, respectively. The three most relevant enzymatic detoxification systems (mixed-function oxidases (MFO), glutathione S-tranferases (GST) and esterases (EST)) were studied for neonate larvae. In eggs, 96% of the field populations showed a significantly lower efficacy when compared with the susceptible strain (S_Spain) and the most effective insecticides were fenoxycarb and thiacloprid. In neonate larvae, a significant loss of susceptibility to the insecticides was detected. Flufenoxuron, azinphos-methyl and phosmet showed the lowest efficacy, while lambda-cyhalothrin, alpha-cypermethrin and chlorpyrifos-ethyl showed the highest. Biochemical assays showed that the most important enzymatic system involved in insecticide detoxification was MFO, with highest enzymatic activity ratios (5.1–16.6 for neonates from nine field populations). An enhanced GST and EST activities was detected in one field population, with enzymatic activity ratios of threefold and fivefold for GST and EST, respectively, when compared with the susceptible strain. The insecticide bioassays showed that the LC90 used were effective as diagnostic concentrations. Measures of MFO activity alongside bioassays with insecticide diagnostic concentrations could be used as tools for monitoring insecticide resistance in neonate larvae of C. pomonella.

Perceptions of twelve-step mutual-help groups and their associations with motivation, treatment attendance and alcohol outcomes among chronically homeless individuals with alcohol problems.

BACKGROUND: Twelve-step mutual-help groups (TMGs) are among the most available forms of support for homeless individuals with alcohol problems. Qualitative research, however, has suggested that this population often has negative perceptions of these groups, which has been shown to be associated with low TMG attendance. It is important to understand this population's perceptions of TMGs and their association with alcohol outcomes to provide more appropriate and better tailored programming for this multiply affected population. The aims of this cross-sectional study were to (a) qualitatively examine perception of TMGs in this population and (b) quantitatively evaluate its association with motivation, treatment attendance and alcohol outcomes. METHODS: Participants (N=62) were chronically homeless individuals with alcohol problems who received single-site Housing First within a larger evaluation study. Perceptions of TMGs were captured using an open-ended item. Quantitative outcome variables were created from assessments of motivation, treatment attendance and alcohol outcomes. RESULTS: Findings indicated that perceptions of TMGs were primarily negative followed by positive and neutral perceptions, respectively. There were significant, positive associations between perceptions of TMGs and motivation and treatment attendance, whereas no association was found for alcohol outcomes. CONCLUSIONS: Although some individuals view TMGs positively, alternative forms of help are needed to engage the majority of chronically homeless individuals with alcohol problems.

Disaster recovery of business critical 3-tiered ERP applications: Disaster Recovery of Nokia Groups SAP R/3

Nykyaikaisessa liiketoimintaympäristössä yritysten kriittisiksi resursseiksi ovat muodostuneet liiketoimintaa tukevat tietojärjestelmät. Mahdollisuus hyödyntää näitä resursseja riippuu ko. liiketoiminnalle kriittisten järjestelmien luotettavuudesta ja hyödynnettävien sovellusten saatavuudesta. Eräs tilanne jossa järjestelmien kyky tukea todellisia liiketoimintaprosesseja vaarantuu on katastrofi. Vaikutukseltaan katastrofi voi olla paikallinen tai kattaa laajojakin alueita. Eri tyyppisiin katastrofeihin on varauduttava niiden edellyttämin tavoin. Eräs kriittisten tietojärjestelmien arkkitehtuuriin vaikuttanut trendi 90-luvulla on ollut client/server lähestymistapa. Client/server paradigman mukaan sovellus jaetaan tasoihin siten että esitys-, sovellus- ja tietokantakerrokset voidaan erottaa fyysisesti toisistaan näiden silti muodostaessa loogisesti yhtenäisen kokonaisuuden. Liiketoiminnan näkökulmasta 90- luvun mullistavia IT-uutuuksia olivat toiminnanohjausjärjestelmät, joiden avulla oli mahdollista hallita koko tuotantoketjua ja muita prosessikokonaisuuksia lähes reaaliajassa. Monikerroksisten toiminnanohjausjärjestelmien luotettavuus on osoittautunut haastavavaksi sillä kaikkien kerrosten suojaaminen kaikilta mahdollisilta katastrofeilta täydellisesti on nykyisellä teknologialla mahdotonta. Kompromissien tekemiseksi on oltava selvillä kunkin menetetyn prosessin aiheuttamista taloudellisista ja liiketoiminnallisista vaikutuksista. Tämän vuoksi juuri toiminnanohjausjärjestelmät ovat mielenkiintoisia, vaikuttavathan ne liiketoimintaprosesseihin läpi koko yrityksen prosessiketjun. Monikerroksisten client/server arkkitehtuuriin pohjautuvien toiminnanohjausjärjestelmien suojaamisessa katastrofeilta onkin sovellettava useita tekniikoita ja teknologioita, ja yhdistettävä kokonaisuus prosessikehykseen. Näin voidaan luoda suunnitelmallinen osa IT strategiaa, joka ottaa kantaa liiketoiminnan jatkuvuuteen katastrofitilanteessa ja mahdollistaa nopean ja täydellisen palautumisen kaikissa olosuhteissa.