Impaired CD8+ T-Cell Reactivity against Viral Antigens in Cancer Patients with Solid Tumors

Abstract. : Background: : Patients with hematological malignancies are at increased risk for various infections. In patients with solid cancer, a variety of immunosuppressive mechanisms affecting T-cell response are described. We hypothesized that patients with advanced solid tumors may exhibit an impaired recognition of viral antigens. To test this, the capability of CD8+ T cells to recognize recall antigens from influenza and vaccinia virus was compared in patients and healthy individuals. Since all patients and most of the healthy individuals had been vaccinated against vaccinia years ago, comparison of the two groups was expected to be especially informative with respect to distinct effector T-cell reactivity. Materials and Methods: : Our test population included 16 healthy individuals and 12 patients with advanced solid cancers who were currently not receiving chemotherapy. We stimulated peripheral blood mononuclear cells (PBMC) ex vivo with the well-characterized influenza A matrix 58-66 peptide and the immunogenic and HLA-A*0201 restricted peptide epitope SLSAYIIRV derived from the modified vaccinia virus Ankara (MVA). A specific CD8+ T-cell reactivity was determined by quantitative real-time polymerase chain reaction (qRT-PCR) measuring changes in interferon gamma (IFN-γ) mRNA expression levels. Results: : We found that significantly fewer cancer patients than healthy individuals exhibited specific T-cell recognition of the vaccinia epitope (25% and 69%, respectively). In addition, strength of the T-cell responses against both viral peptides was significantly reduced in cancer patients. Conclusion: : Patients with advanced tumors are less likely to mount a T-cell response against viral epitopes. These findings may have implications for the design of immunotherapeutic interventions against virus-induced diseases, including tumor

Policy instruments and welfare state reform

A core, but so far untested, proposition of the new politics perspective, originally introduced by Paul Pierson, is that welfare state cutbacks will be implemented using so-called ‘invisible’ policy instruments, for example, a change in indexation rules. Expansion should, by implication, mainly happen using ‘visible’ policy instruments, for example, a change in nominal benefits. We have coded 1030 legislative reforms of old-age pensions and unemployment protection in Britain, Denmark, Finland and Germany from 1974 to 2014. With this unique data at hand, we find substantial support for this crucial new politics proposition

An unusual foreign body migrating through time and tissues

BACKGROUND: Beside infections, foreign body incidences are amongst the most frequently encountered pathologies in pediatric otolaryngology. While inhaled foreign bodies represent an acute emergency, symptoms of ingested foreign bodies sometimes appear with some delay. Typically fishbones tend to go unnoticed in a first examination and become symptomatic by fever, odynodyspahgia and torticollis. Exceptionally, foreign bodies migrate and become manifest with a considerable delay. CASE REPORT: We present a case of a young girl who presented with an unusual foreign body which migrated through the cervical tissues causing repeated cervical tumescence's before being diagnosed. CONCLUSION: Repeated cervical abscesses or tumescence's in children or young patients should alert the treating physician to seek for an underlying pathology such as unnoticed foreign bodies or malformations (e.g. cysts). Further the scarce literature on these migrating foreign bodies is discussed

A critical review of the formation of mono- and dicarboxylated metabolic intermediates of alkylphenol polyethoxylates during wastewater treatment and their environmental significance

This is the author's accepted manuscript. The final published article is available from the link below. Copyright @ 2010 Taylor & Francis.Alkylphenoxyacetic acids, the metabolic biodegradation products of alkylphenol ethoxylates, are commonly found in wastewaters and sewage effluents. These persistent hydrophilic derivatives possess intrinsic estrogenic activity, which can mimic natural hormones. Their concentrations increase through the sewage treatment works as a result of biodegradation and biotransformation, and when discharged can disrupt endocrine function in fish. These acidic metabolites represent the dominant alkylphenolic compounds found in wastewater effluent and their presence is cause for concern as, potentially, through further biotransformation and biodegradation, they can act as sources of nonylphenol, which is toxic and estrogenic. The authors aim to assess the mechanisms of formation as well as elimination of alkylphenoxyacetic acids within conventional sewage treatment works with the emphasis on the activated sludge process. In addition, they evaluate the various factors influencing their degradation and formation in laboratory scale and full-scale systems. The environmental implications of these compounds are considered, as is the need for tertiary treatment processes for their removal

Influence of operating parameters on the biodegradation of steroid estrogens and nonylphenolic compounds during biological wastewater treatment processes

This document is the unedited author's version of a Submitted Work that was subsequently accepted for publication in Environmental Science & Technology, copyright © American Chemical Society after peer review. To access the final edited and published work see http://pubs.acs.org/doi/abs/10.1021/es901612v.This study investigated operational factors influencing the removal of steroid estrogens and nonylphenolic compounds in two sewage treatment works, one a nitrifying/denitrifying activated sludge plant and the other a nitrifying/denitrifying activated sludge plant with phosphorus removal. Removal efficiencies of >90% for steroid estrogens and for longer chain nonylphenol ethoxylates (NP4−12EO) were observed at both works, which had equal sludge ages of 13 days. However, the biological activity in terms of milligrams of estrogen removed per day per tonne of biomass was found to be 50−60% more efficient in the nitrifying/denitrifying activated sludge works compared to the works which additionally incorporated phosphorus removal. A temperature reduction of 6 °C had no impact on the removal of free estrogens, but removal of the conjugated estrone-3-sulfate was reduced by 20%. The apparent biomass sorption (LogKp) values were greater in the nitrifying/denitrifying works than those in the nitrifying/denitrifying works with phosphorus removal for both steroid estrogens and nonylphenolic compounds possibly indicating a different cell surface structure and therefore microbial population. The difference in biological activity (mg tonne−1 d−1) identified in this study, of up to seven times, suggests that there is the potential for enhancing the removal of estrogens and nonylphenols if more detailed knowledge of the factors responsible for these differences can be identified and maximized, thus potentially improving the quality of receiving waters.Public Utilities Board (Singapore), Anglian Water Ltd, Severn Trent Water Ltd, Thames Water Utilities Ltd, United Utilities 393 Plc and Yorkshire Water Services

Repeatability of traits for characterizing feed intake patterns in dairy goats: a basis for phenotyping in the precision farming context

International audienceIn ruminants, feeding behaviour variables are parameters involved in feed efficiency that show variation among individuals. This study aimed to evaluate during the first two production cycles in ruminants the repeatability of feed intake pattern, which is an important aspect of feeding behaviour. Thirty-five dairy goats from Alpine or Saanen breeds were housed in individual pens at four periods (end of first gestation, middle of first and second lactations and middle of second gestation which is also the end of first lactation) and fed a total mixed ration (TMR) ad libitum. Individual cumulative dry matter intake (DMI) was automatically measured every 2 min during the last 4 days of each period. Feed intake pattern was characterized by several measures related to the quantity of feed eaten or to the rate of intake during the 15 h following the afternoon feed delivery. Two main methods were used: modelling cumulative DMI evolution by an exponential model or by a segmentation-clustering method. The goat ability to sort against dietary fibre was also evaluated. There was a very good repeatability of the aggregate measures between days within a period for a given goat estimated by the day effect within breed and goat, tested on the residual variance (P > 0.95). The correlations between periods were the highest between the second and either the third or fourth periods. With increasing age, goats sorted more against the fibrous part of the TMR and increased their initial rate of intake. Alpine goats ate more slowly than Saanen goats but ate during a longer duration. Principal component analysis (PCA) was performed on all the aggregate measures of feed intake patterns. The factor score plots generated by the PCA highlighted the opposition between the different measures of feed intake patterns and the sorting behaviour. The projection of the animals on the scoring plots showed a breed effect and that there was a continuum for the feed intake pattern of goats. In conclusion, this study showed that the feed intake pattern was highly repeatable for an animal in a given period and between periods. This means that phenotyping goats in a younger age might be of interest, either to select them on feeding behaviour and choose preferentially the slow eaters or to adapt the quantity offered and restrict feed delivery to the fast eaters in order to increase feed efficiency and welfare by limiting the occurrence of acidosis, for example

Installing hydrolytic activity into a completely <i>de novo </i>protein framework

The design of enzyme-like catalysts tests our understanding of sequence-to-structure/function relationships in proteins. Here we install hydrolytic activity predictably into a completely de novo and thermostable α-helical barrel, which comprises seven helices arranged around an accessible channel. We show that the lumen of the barrel accepts 21 mutations to functional polar residues. The resulting variant, which has cysteine–histidine–glutamic acid triads on each helix, hydrolyses p-nitrophenyl acetate with catalytic efficiencies that match the most-efficient redesigned hydrolases based on natural protein scaffolds. This is the first report of a functional catalytic triad engineered into a de novo protein framework. The flexibility of our system also allows the facile incorporation of unnatural side chains to improve activity and probe the catalytic mechanism. Such a predictable and robust construction of truly de novo biocatalysts holds promise for applications in chemical and biochemical synthesis

Temperature-Resolved Surface Infrared Spectroscopy of CO on Rh(111) and (2 × 1)-O/Rh(111)

Heterogeneously catalyzed reactions over transition metal surfaces are pillars of chemical industry and account for a significant fraction of the global energy demand. CO oxidation provides insight into the relative reactivity of various oxygenaceous surface phases, and it is necessary to first understand where it binds to the surface and the nature of the local environment to develop robust mechanistic pictures of the reaction. Surface IR spectroscopy is a quantitative technique that also provides information about the binding sites and chemical environments of the adsorbed CO molecules. Here, we report results from a study of CO sticking to clean Rh(111) and (2 × 1)-O/Rh(111) that shows that the intensity of the IR absorption was not linear with coverage and is an important consideration for further studies of the catalytic surface