CTL induction by cross-priming is restricted to immunodominant epitopes

CTL are induced by two pathways, i.e. direct priming, where tumor cells present tumor antigens to naïve specific CTL, and cross-priming, where professional APC cross-present captured tumor antigens to CTL. Here, we examined direct priming versus cross-priming after immunizing (H-2(b) x H-2(d)) F1 mice with either H-2(b) or H-2(d) positive tumor cells transfected with the GP or nucleoprotein (NP) of lymphocytic choriomeningitis virus (LCMV). Cross-priming was observed for the immunodominant epitopes LCMV-gp33 and -np118, although direct induction resulted in higher CTL frequencies. In contrast, CTL specific for the subdominant epitopes LCMV-gp283 or -np396 were induced only if epitopes were presented directly on MHC class I molecules of the immunizing cell. The broader repertoire and the higher CTL frequencies induced after vaccination with haplotype-matched tumor cells resulted in more efficient anti-tumor and antiviral protection. Firstly, our results indicate that certain virus and tumor antigens may not be detected by CD8(+) T cells because of impaired cross-priming. Secondly, efficient cross-priming contributes to the immunodominant nature of a tumor-specific CTL epitope. Thirdly, vaccine strategies using autologous or syngenic antigen-expressing cells induce a broader repertoire of tumor-specific CTL and higher CTL frequencies.

Victims of War must be loyal to deserve protection: International law and national legislation on enemy aliens 1907-1918

In international law the internment of civilians has only been regulated in writing in the context of the 4th Geneva Convention of 1949. Nevertheless this did not mean that civilians were not protected by at least some rules of customary international law before that date and especially in World War I. Furthermore specialists of international law expected states – at least those considered to be part of the community of civilized nations – to continue to treat all men equal before the law even in wartime. As research already conducted (Bird, Panayi, Fischer) has shown, this was not the case during World War I. Based on these findings the presentation proposed here wants to look into the development of international law and into some national preparations for treating so called “enemy aliens” in the period before 1914 (Austria-Hungary, Australia, United Kingdom), in order to see to what extent principles of international law protecting civilians from the consequences of war can be detected in the pre-war preparations. As far as can be judged so far the issue of loyalty was central in this context. Looking at the war itself, the presentation proposed here will try to look at how far the principles of international law alluded to above continued to influence the policies on “enemy aliens” in the countries mentioned and to see, how the International Committee of the Red Cross tried to use them to legitimize and expand its protective policies in regard to civilians interned in belligerent as well as neutral countries throughout the war.

Appreciation of nature and appreciation of environmental protection: How stable are these attitudes and which comes first?

Introduction. – Attitude toward nature and attitude toward environmental protection are two separate but correlated attitudes. Little is known about the two attitudes’ stability/volatility over time, despite the practical value of such knowledge. Objectives & method. – Using longitudinal survey data from 251 adults in a cross-lagged structural equation model, we assessed the degree of spontaneous (i.e., unprompted) change in the two attitudes. We also considered whether such change could provide evidence regarding causal direction; causation could go in either of two directions between the two attitudes, or it could even be bi-directional. Results. – We corroborated the substantive connection between attitude toward nature and attitude toward environmental protection; however, the absence of change in the attitudes despite the passage of two years disallows reliable statements about causal direction. Conclusion. – It is possible to protect the environment by encouraging appreciation of nature, but change in attitude toward nature and attitude toward environmental protection may be difficult to achieve with mature individuals.

A cross-sectional analysis of the association between polycyclic aromatic hydrocarbons and diesel particulate matter exposures and hypertension among individuals of Mexican origin residing in Houston, TX

Background. Research has shown that elevations of only 10 mmHg diastolic blood pressure (BP) and 5 mmHg systolic BP are associated with substantial (as large as 50%) increases in risks for cardiovascular disease, a leading cause of death, worldwide. Epidemiological studies have found that particulate matter (PM) increases blood pressure (BP) and many biological mechanisms which may suggest that the organic matter of PM contributes to the increase in BP. To understand components of PM which may contribute to the increase in BP, this study focuses on diesel particulate matter (DPM) and polycyclic aromatic hydrocarbons (PAHs). To our knowledge, there have been only four epidemiological studies on BP and DPM, and no epidemiological studies on BP and PAHs. ^ Objective. Our objective was to evaluate the association between prevalent hypertension and two ambient exposures: DPM and PAHs amongst the Mano a Mano cohort. ^ Methods. The Mano a Mano cohort which was established by the M.D. Anderson Cancer Center in 2001, is comprised of individuals of Mexican origin residing in Houston, TX. Using geographical information systems, we linked modeled annual estimates of PAHs and DPM at the census track level from the U.S. Environmental Protection Agency's National-Scale Air Toxics Assessment to residential addresses of cohort members. Mixed-effects logistic regression models were applied to determine associations between DPM and PAHs and hypertension while adjusting for confounders. ^ Results. Ambient levels of DPM, categorized into quartiles, were not statistically associated with hypertension and did not indicate a dose response relationship. Ambient levels of PAHs, categorized into quartiles, were not associated with hypertension, but did indicate a dose response relationship in multiple models (for example: Q2: OR = 0.98; 95% CI, 0.73–1.31, Q3: OR = 1.08; 95% CI, 0.82–1.41, Q4: OR = 1.26; 95% CI, 0.94–1.70). ^ Conclusion. This is the first assessment to analyze the relationship between ambient levels of PAHs and hypertension and it is amongst a few studies investigating the association between ambient levels of DPM and hypertension. Future analyses are warranted to explore the effects DPM and PAHs using different categorizations in order to clarify their relationships with hypertension.^

Full scale test for explosion water barriers in small cross-section galleries

Underground coal mines explosions generally arise from the inflammation of a methane/air mixture. This explosion can also generate a subsequent coal dust explosion. Traditionally such explosions have being fought eliminating one or several of the factors needed by the explosion to take place. Although several preventive measures are taken to prevent explosions, other measures should be considered to reduce the effects or even to extinguish the flame front. Unlike other protection methods that remove one or two of the explosion triangle elements, namely; the ignition source, the oxidizing agent and the fuel, explosion barriers removes all of them: reduces the quantity of coal in suspension, cools the flame front and the steam generated by vaporization removes the oxygen present in the flame. Passive water barriers are autonomous protection systems against explosions that reduce to a satisfactory safety level the effects of methane and/or flammable dust explosions. The barriers are activated by the pressure wave provoked in the explosion destroying the barrier troughs and producing a uniform dispersion of the extinguishing agent throughout the gallery section in quantity enough to extinguish the explosion flame. Full scale tests have been carried out in Polish Barbara experimental mine at GIG Central Mining Institute in order to determine the requirements and the optimal installation conditions of these devices for small sections galleries which are very frequent in the Spanish coal mines. Full scale tests results have been analyzed to understand the explosion timing and development, in order to assess on the use of water barriers in the typical small crosssection Spanish galleries. Several arrangements of water barriers have been designed and tested to verify the effectiveness of the explosion suppression in each case. The results obtained demonstrate the efficiency of the water barriers in stopping the flame front even with smaller amounts of water than those established by the European standard. According to the tests realized, water barriers activation times are between 0.52 s and 0.78 s and the flame propagation speed are between 75 m/s and 80 m/s. The maximum pressures (Pmax) obtained in the full scale tests have varied between 0.2 bar and 1.8 bar. Passive barriers protect effectively against the spread of the flame but cannot be used as a safeguard of the gallery between the ignition source and the first row of water troughs or bags, or even after them, as the pressure could remain high after them even if the flame front has been extinguished.

Influencia del viento transversal en sistemas ferroviarios = Cross-wind effects on railway infrastructure

El viento, como factor medio-ambiental, ha sido objeto de numerosos estudios por los efectos que induce tanto en vehículos como en estructuras. Dentro del ámbito ferroviario, las cargas aerodinámicas debidas a la acción del viento transversal pueden poner en compromiso la seguridad de los vehículos en circulación, pudiendo llegar a ocasionar el vuelco del mismo. Incluso el sistema de cables encargado de realizar el suministro eléctrico necesario para la tracción del tren, conocido como catenaria, es sensible a la acción del viento. De hecho, al igual que ocurre en ciertas estructuras de cables, la interacción entre las fuerzas aerodinámicas no estacionarias y la catenaria puede ocasionar la aparición de oscilaciones de gran amplitud debido al fenómeno de galope. Una forma sencilla de reducir los efectos no deseados de la acción del viento, es la instalación de barreras cortavientos aguas arriba de la zona que se desea proteger. La instalación de estos dispositivos, reduce la velocidad en la estela generada, pero también modifica las propiedades del flujo dentro de la misma. Esta alteración de las condiciones del flujo puede contribuir a la aparición del fenómeno de galope en estructuras caracterizadas por su gran flexibilidad, como la catenaria ferroviaria. Estos dos efectos contrapuestos hacen evidente la importancia de mantener cierta visión global del efecto introducido por la instalación de barreras cortavientos en la plataforma ferroviaria. A lo largo de este documento, se evalúa desde un enfoque multidisciplinar el efecto inducido por las barreras cortavientos en varios subsistemas ferroviarios. Por un lado se analizan las mejoras en la estabilidad lateral del vehículo mediante una serie de ensayos en túnel de viento. La medición de la distribución de presiones en la superficie de un modelo bidimensional de vehículo ferroviario proporciona una buena estimación del nivel de protección que se consigue en función de la altura de una barrera cortavientos. Por otra parte, se analiza la influencia del mismo juego de barreras cortavientos en las características del flujo situado sobre la plataforma ferroviaria, mediante la utilización de anemometría de hilo caliente (HWA) y velocimetría de imágenes de párticulas (PIV). En particular se centra la atención en las características en la posición correspondiente a los hilos conductores de la catenaria. En la última parte del documento, se realiza un análisis simplificado de la aparición oscilaciones en la catenaria, por el efecto de la inestabilidad de galope. La información obtenida sobre las características del flujo se combinan con las propiedades aerodinámicas del hilo de contacto, obtenidas en mediante una serie de ensayos en túnel de viento. De esta manera se realiza una evaluación del riesgo a la aparición de este tipo de inestabilidad aeroeslástica aplicada a una catenaria ferroviaria situada sobre un viaducto tipo. ABSTRACT Wind as an environmental factor may induce undesirable effects on vehicles and structures. The analysis of those effects has caught the attention of several researchers. Concerning the railway system, cross-wind induces aerodynamic loads on rolling stock that may increase the overturning risk of the vehicle, threatening its safe operation. Even the cable system responsible to provide the electric current required for the train traction, known as the railway overhead or catenary, is sensitive to the wind action. In fact, the interaction between the unsteady aerodynamic forces and the railway overhead may trigger the development of undamped oscillations due to galloping phenomena. The inclusion of windbreaks upstream the area that needs wind protection is a simple mean to palliate the undesirable effects caused by the wind action. Although the presence of this wind protection devices reduces the wind speed downstream, they also modify the flow properties inside their wake. This modification on the flow characteristics may ease the apparition of the galloping phenomena on flexible structures, such as the railway overhead. This two opposite effects require to maintain a global perspective on the analysis of the influence of the windbreak presence. In the present document, a multidisciplinary analysis on the effect induced by windbreaks on several railways subsystems is conducted. On the one hand, a set of wind tunnel tests is conducted to assess the improvement on the rolling stock lateral stability. The qualitative estimation of the shelter effect, as function of the windbreak height, is established through the pressure distribution measured on the surface of a two-dimensional train model. On the other hand, the flow properties above the railway platform are assessed using the same set of windbreaks. Two experimental techniques are used to measure the flow properties, hot-wire anemometry (HWA) and particle image velocimetry (PIV). In particular, the attention is focused on the flow characteristics on the contact wire location. A simplified analysis on the catenary oscillations due to galloping phenomena is conducted in the last part of the document. Both, the flow characterization performed via PIV and the aerodynamic properties of the contact wire cross-section are combined. In this manner, the risk of the aeroelastic instabilities on a railway overhead placed on a railway bridge is assessed through a practical application.

Phase variation of the lpf operon is a mechanism to evade cross-immunity between Salmonella serotypes

Conventional wisdom holds that phase variation is a mechanism for immune evasion. However, despite fimbrial phase variation, mice previously exposed to Salmonella typhimurium are protected against a subsequent challenge. We evaluated whether lpf phase variation instead may be a mechanism to evade cross-immunity between Salmonella serotypes. Mice were immunized orally with S. typhimurium aroA mutants either that expressed the lpf operon (phase-on variant) or in which the entire lpf operon had been removed by deletion. During a subsequent challenge with virulent Salmonella enteritidis a selection against lpf phase-on variants was observed in mice previously exposed to S. typhimurium long polar fimbriae. Vaccination with S. typhimurium did not confer protection against challenge with S. enteritidis, presumably because lpf phase-off variants were able to evade cross-immunity. We propose that lpf phase variation is a mechanism to evade cross-immunity between Salmonella serotypes, thereby allowing their coexistence in a host population.

Cross-cutting environmental laws : a guide for federal/state project officers.

Mode of access: Internet.

Effects of marine reserve protection on the mud crap Scylla serrata in a sex-biased fishery in subtropical Australia

The impact of sex-biased fishing and marine reserve protection on the mud crab Scylla serrata was examined by comparing the catch rates (catch-per-unit-effort, CPUE), mean size, sex ratios and movement of crabs in 2 coastal marine reserves (1.9 and 5.7 km(2)) and 4 fished non-reserve sites in subtropical Australia. Five years after closure, both marine reserves supported higher catch rates and a larger mean size of S. serrata than non-reserve sites. Males dominated catches of S. serrata in both marine reserves, where CPUE was at least twice as high within the reserves compared to non-reserve sites. Male crabs were also 10% larger in the reserves compared to adjacent fished areas, and of the total male catch, over 70% were equal to or greater than legal size compared to less than 50% outside the reserves. The sex ratio of S. serrata was skewed towards females in all nonreserve sites, which was most likely a result of the ban on taking female S. serrata in Moreton Bay. As only male crabs of >= 15 cm CW made up the S. serrata fishery in Moreton Bay, sex ratios of mature male and female crabs were examined, revealing a strong skew (2:1) towards mature males in both marine reserves. Of the 472 S. serrata captured in this study, 338 were tagged in the reserves in order to document movement of the crabs between the reserve and non-reserve sites. Of the 37 recaptured crabs, 73% were recorded inside the reserves, with some spillover (i.e. cross-boundary movement) of crabs recorded in fished areas. This study demonstrates the effectiveness of small (< 6 km(2)) marine reserves for sex-biased exploited fisheries species.

Interagency collaboration between child protection and mental health services: Practices, attitudes and barriers

Objective: The aim of this paper is to examine some of the factors that facilitate and hinder interagency collaboration between child protection services and mental health services in cases where there is a parent with a mental illness and there are protection concerns for the child(ren). The paper reports on agency practices, worker attitudes and experiences, and barriers to effective collaboration. Method: A self-administered, cross-sectional survey was developed and distributed via direct mail or via line supervisors to workers in statutory child protection services, adult mental health services, child and youth mental health services, and Suspected Child Abuse and Neglect (SCAN) Teams. There were 232 completed questionnaires returned, with an overall response rate of 21%. Thirty-eight percent of respondents were statutory child protection workers. 39% were adult mental health workers, 16% were child and youth mental health workers, and 4% were SCAN Team medical officers (with 3% missing data). Results: Analysis revealed that workers were engaging in a moderate amount of interagency contact, but that they were unhappy with the support provided by their agency. Principle components analysis and multivariate analysis of variance (MANOVA) on items assessing attitudes toward other workers identified four factors, which differed in rates of endorsement: inadequate training, positive regard for child protection workers, positive regard for mental health workers, and mutual mistrust (from highest to lowest level of endorsement). The same procedure identified the relative endorsement of five factors extracted from items about potential barriers: inadequate resources, confidentiality, gaps in interagency processes, unrealistic expectations, and professional knowledge domains and boundaries. Conclusions: Mental health and child protection professionals believe that collaborative practice is necessary; however, their efforts are hindered by a lack of supportive structures and practices at the organizational level. (c) 2005 Published by Elsevier Ltd.

Assessment of different formulations of oral Mycobacterium bovis Bacille Calmette-Guerin (BCG) vaccine in rodent models for immunogenicity and protection against aerosol challenge with M-bovis

Bovine tuberculosis (bTB) caused by infection with Mycobacterium bovis is causing considerable economic loss to farmers and Government in the United Kingdom as its incidence is increasing. Efforts to control bTB in the UK are hampered by the infection in Eurasian badgers (Metes metes) that represent a wildlife reservoir and source of recurrent M. bovis exposure to cattle. Vaccination of badgers with the human TB vaccine, M. bovis Bacille Calmette-Guerin (BCG), in oral bait represents a possible disease control tool and holds the best prospect for reaching badger populations over a wide geographical area. Using mouse and guinea pig models, we evaluated the immunogenicity and protective efficacy, respectively, of candidate badger oral vaccines based on formulation of BCG in lipid matrix, alginate beads, or a novel microcapsular hybrid of both lipid and alginate. Two different oral doses of BCG were evaluated in each formulation for their protective efficacy in guinea pigs, while a single dose was evaluated in mice. In mice, significant immune responses (based on lymphocyte proliferation and expression of IFN-gamma) were only seen with the lipid matrix and the lipid in alginate microcapsular formulation, corresponding to the isolation of viable BCG from alimentary tract lymph nodes. In guinea pigs, only BCG formulated in lipid matrix conferred protection to the spleen and lungs following aerosol route challenge with M. bovis. Protection was seen with delivery doses in the range 10(6)-10(7) CFU, although this was more consistent in the spleen at the higher dose. No protection in terms of organ CFU was seen with BCG administered in alginate beads or in lipid in alginate microcapsules, although 10(7) in the latter formulation conferred protection in terms of increasing body weight after challenge and a smaller lung to body weight ratio at necropsy. These results highlight the potential for lipid, rather than alginate, -based vaccine formulations as suitable delivery vehicles for an oral BCG vaccine in badgers.

Interoperability of Cross-Border European Egovernment Services: Some Design Issues

The authors analyse some of the research outcomes achieved during the implementation of the EC GUIDE research project “Creating an European Identity Management Architecture for eGovernment”, as well as their personal experience. The project goals and achievements are however considered in a broader context. The key role of Identity in the Information Society was emphasised, that the research and development in this field is in its initial phase. The scope of research related to Identity, including the one related to Identity Management and Interoperability of Identity Management Systems, is expected to be further extended. The authors analyse the abovementioned issues in the context established by the EC European Interoperability Framework (EIF) as a reference document on interoperability for the Interoperable Delivery of European eGovernment Services to Public Administrations, Business and Citizens (IDABC) Work Programme. This programme aims at supporting the pan-European delivery of electronic government services.

Targeted Brain Derived Neurotropic Factors (BDNF) Delivery across the Blood-Brain Barrier for Neuro-Protection Using Magnetic Nano Carriers: An In-Vitro Study

Parenteral use of drugs; such as opiates exert immunomodulatory effects and serve as a cofactor in the progression of HIV-1 infection, thereby potentiating HIV related neurotoxicity ultimately leading to progression of NeuroAIDS. Morphine exposure is known to induce apoptosis, down regulate cAMP response element-binding (CREB) expression and decrease in dendritic branching and spine density in cultured cells. Use of neuroprotective agent; brain derived neurotropic factor (BDNF), which protects neurons against these effects, could be of therapeutic benefit in the treatment of opiate addiction. Previous studies have shown that BDNF was not transported through the blood brain barrier (BBB) in-vivo.; and hence it is not effectivein-vivo. Therefore development of a drug delivery system that can cross BBB may have significant therapeutic advantage. In the present study, we hypothesized that magnetically guided nanocarrier may provide a viable approach for targeting BDNF across the BBB. We developed a magnetic nanoparticle (MNP) based carrier bound to BDNF and evaluated its efficacy and ability to transmigrate across the BBB using an in-vitro BBB model. The end point determinations of BDNF that crossed BBB were apoptosis, CREB expression and dendritic spine density measurement. We found that transmigrated BDNF was effective in suppressing the morphine induced apoptosis, inducing CREB expression and restoring the spine density. Our results suggest that the developed nanocarrier will provide a potential therapeutic approach to treat opiate addiction, protect neurotoxicity and synaptic density degeneration.

Coproducing flood risk management through citizen involvement: insights from cross-country comparison in Europe

Across Europe, citizens are increasingly expected to participate in the implementation of flood risk management (FRM), by engaging in voluntary-based activities to enhance preparedness, implementing property-level measures, and so forth. Although citizen participation in FRM decision making is widely addressed in academic literature, citizens’ involvement in the delivery of FRM measures is comparatively understudied. Drawing from public administration literature, we adopted the notion of “coproduction” as an analytical framework for studying the interaction between citizens and public authorities, from the decision-making process through to the implementation of FRM in practice. We considered to what extent coproduction is evident in selected European Union (EU) member states, drawing from research conducted within the EU project STAR-FLOOD (Strengthening and Redesigning European Flood Risk Practices towards Appropriate and Resilient Flood Risk Governance Arrangements). On the basis of a cross-country comparison between Flanders (Belgium), England (United Kingdom), France, the Netherlands, and Poland, we have highlighted the varied forms of coproduction and reflected on how these have been established within divergent settings. Coproduction is most prominent in discourse and practice in England and is emergent in France and Flanders. By contrast, FRM in the Netherlands and Poland remains almost exclusively reliant on governmental protection measures and thereby consultation-based forms of coproduction. Analysis revealed how these actions are motivated by different underlying rationales, which in turn shape the type of approaches and degree of institutionalization of coproduction. In the Netherlands, coproduction is primarily encouraged to increase societal resilience, whereas public authorities in the other countries also use it to improve cost-efficiency and redistribute responsibilities to its beneficiaries.