Binary metal oxides for composite ultrafiltration membranes

A new ultrafiltration membrane was developed by the incorporation of binary metal oxides inside polyethersulfone. Physico-chemical characterization of the binary metal oxides demonstrated that the presence of Ti in the TiO2?ZrO2 system results in an increase of the size of the oxides, and also their dispersity. The crystalline phases of the synthesized binary metal oxides were identified as srilankite and zirconium titanium oxide. The effect of the addition of ZrO2 can be expressed in terms of the inhibition of crystal growth of anocrystalline TiO2 during the synthesis process. For photocatalytic applications the band gap of the synthesized semiconductors was determined, confirming a gradual increase (blue shift) in the band gap as the amount of Zr loading increases. Distinct distributions of binary metal oxides were found along the permeation axis for the synthesized membranes. Particles with Ti are more uniformly dispersed throughout the membrane cross-section. The physico-chemical characterization of membranes showed a strong correlation between some key membrane properties and the spatial particle distribution in the membrane structure. The proximity of metal oxide fillers to the membrane surface determines the hydrophilicity and porosity of modified membranes. Membranes incorporating binary metal oxides were found to be promising candidates for wastewater treatment by ultrafiltration, considering the observed improvement influx and anti-fouling properties of doped membranes. Multi-run fouling tests of doped membranes confirmed the stability of permeation through membranes embedded with binary TiO2?ZrO2 particles

CD8 T-cell responses against the immunodominant Theileria parvapeptide Tp249-59 are composed of two distinct populations specific for overlapping 11-mer and 10-mer epitopes

Immunity against Theileria parva is associated with CD8 T-cell responses that exhibit immunodominance, focusing the response against limited numbers of epitopes. As candidates for inclusion in vaccines, characterization of responses against immunodominant epitopes is a key component in novel vaccine development. We have previously demonstrated that the Tp249–59 and Tp1214–224 epitopes dominate CD8 T-cell responses in BoLA-A10 and BoLA-18 MHC I homozygous animals, respectively. In this study, peptide–MHC I tetramers for these epitopes, and a subdominant BoLA-A10-restricted epitope (Tp298–106), were generated to facilitate accurate and rapid enumeration of epitope-specific CD8 T cells. During validation of these tetramers a substantial proportion of Tp249–59-reactive T cells failed to bind the tetramer, suggesting that this population was heterogeneous with respect to the recognized epitope. We demonstrate that Tp250–59 represents a distinct epitope and that tetramers produced with Tp50–59 and Tp49–59 show no cross-reactivity. The Tp249–59 and Tp250–59 epitopes use different serine residues as the N-terminal anchor for binding to the presenting MHC I molecule. Molecular dynamic modelling predicts that the two peptide–MHC I complexes adopt structurally different conformations and Tcell receptor β sequence analysis showed that Tp249–59 and Tp250–59 are recognized by non-overlapping T-cell receptor repertoires. Together these data demonstrate that although differing by only a single residue, Tp249–59 and Tp250–59 epitopes form distinct ligands for T-cell receptor recognition. Tetramer analysis of T. parva-specific CD8 T-cell lines confirmed the immunodominance of Tp1214–224 in BoLA-A18 animals and showed in BoLA-A10 animals that the Tp249–59 epitope response was generally more dominant than the Tp250–59 response and confirmed that the Tp298–106 response was subdominant

Nanofiltration separation of polyvalent and monovalent anions in desalination brines

This work, as part of a global membrane process for the recovery of alkali and acids from reverse osmosis (RO) desalination brines, focuses on the nanofiltration (NF) separation of polyvalent and monovalent anions, more specifically sulfate and chloride. This pretreatment stage plays a key role in the whole recovery process. Working with model brines simulating the concentration of RO concentrates, 0.2–1.2 M chloride concentration and 0.1 M sulfate concentration, the experimental performance and modeling of the NF separation is reported. The study has been carried out with the NF270 (Dow Filmtec) membrane. The effect of operating pressure (500–2000 kPa), ionic strength (0.4–1.3 M) and chloride initial concentration (0.2–1.2 M) on the membrane separation capacity has been investigated. Finally, the Donnan Steric Pore Model (DSPM) together with experimentally determined parameters, effective pore radius (rp), thickness of the membrane effective layer (d) and effective membrane charge density (Xd), was proved accurate enough to satisfactorily describe the experimental results. In this work we provide for the first time the analysis of partitioning effects and transport mechanism in the NF separation of sulfate and chloride anions in concentrations that simulate those found in RO desalination brines.This work has been financially supported by projects CTQ2008-0690, ENE2010-15585 and CTM2011-23912 (co-financed by ERDF Funds).The authors would like to acknowledge SADYT, S.A. for providing assistance for this work

Nanofiltration of hormone mimicking trace organic contaminants

The removal mechanisms of three hormone mimicking organic compounds by nanofiltration (NF) membranes have been examined. Two NF membranes having different pore size were used in laboratory-scale nanofiltration experiments with feed solutions spiked with a hormone mimicking compound ¾ nonylphenol, tert-butyl phenol, or bisphenol A. Retention of the compounds was determined at various solution chemistries, namely aqueous solution pH, ionic strength, and presence of natural organic matter. The nanofiltration behavior of the selected hormone mimicking compounds appears similar to that of natural hormones as reported in our previous work. While the solution pH can dramatically influence the retention of hormone mimicking compounds by a loose NF membrane, ionic strength does not affect the nanofiltration of such contaminants. However, in the presence of natural organic matter in the feed solution, ionic strength appears to play a significant role in solute-solute and solute-membrane interactions, resulting in increased retention due to partitioning of the hormone mimicking compounds onto organic matter at a higher ionic strength

An Efficient Strategy to Induce and Maintain In Vitro Human T Cells Specific for Autologous Non-Small Cell Lung Carcinoma

BACKGROUND: The efficient expansion in vitro of cytolytic CD8+ T cells (CTLs) specific for autologous tumors is crucial both for basic and translational aspects of tumor immunology. We investigated strategies to generate CTLs specific for autologous Non-Small Cell Lung Carcinoma (NSCLC), the most frequent tumor in mankind, using circulating lymphocytes. PRINCIPAL FINDINGS: Classic Mixed Lymphocyte Tumor Cultures with NSCLC cells consistently failed to induce tumor-specific CTLs. Cross-presentation in vitro of irradiated NSCLC cells by autologous dendritic cells, by contrast, induced specific CTL lines from which we obtained a high number of tumor-specific T cell clones (TCCs). The TCCs displayed a limited TCR diversity, suggesting an origin from few tumor-specific T cell precursors, while their TCR molecular fingerprints were detected in the patient's tumor infiltrating lymphocytes, implying a role in the spontaneous anti-tumor response. Grafting NSCLC-specific TCR into primary allogeneic T cells by lentiviral vectors expressing human V-mouse C chimeric TCRalpha/beta chains overcame the growth limits of these TCCs. The resulting, rapidly expanding CD4+ and CD8+ T cell lines stably expressed the grafted chimeric TCR and specifically recognized the original NSCLC. CONCLUSIONS: This study defines a strategy to efficiently induce and propagate in vitro T cells specific for NSCLC starting from autologous peripheral blood lymphocytes

Selective cancer-germline gene expression in pediatric brain tumors

Cancer-germline genes (CGGs) code for immunogenic antigens that are present in various human tumors and can be targeted by immunotherapy. Their expression has been studied in a wide range of human tumors in adults. We measured the expression of 12 CGGs in pediatric brain tumors, to identify targets for therapeutic cancer vaccines. Real Time PCR was used to quantify the expression of genes MAGE-A1, MAGE-A2, MAGE-A3, MAGE-A4, MAGE-A6, MAGE-A10, MAGE-A12, MAGE-C2, NY-ESO-1 and GAGE-1,2,8 in 50 pediatric brain tumors of different histological subtypes. Protein expression was examined with immunohistochemistry. Fifty-five percent of the medulloblastomas (n = 11), 86% of the ependymomas (n = 7), 40% of the choroid plexus tumors (n = 5) and 67% of astrocytic tumors (n = 27) expressed one or more CGGs. Immunohistochemical analysis confirmed qPCR results. With exception of a minority of tumors, the overall level of CGG expression in pediatric brain tumors was low. We observed a high expression of at least one CGG in 32% of the samples. CGG-encoded antigens are therefore suitable targets in a very selected group of pediatric patients with a brain tumor. Interestingly, glioblastomas from adult patients expressed CGGs more often and at significantly higher levels compared to pediatric glioblastomas. This observation is in line with the notion that pediatric and adult glioblastomas develop along different genetic pathways

Parent-child interactions and adolescent anxiety: a systematic review

Parental behaviours have been implicated in the development and maintenance of anxiety in children and young people; however the degree to which findings apply to adolescents specifically remains unclear. We conducted a systematic review of studies examining the evidence for an association between parental behaviours and adolescent anxiety. Twenty two studies were identified. The results of this systematic review provide fairly consistent preliminary evidence for an association between anxiety and perceived parental control and anxious rearing in adolescence. The findings relating to an association between adolescent anxiety and perceived parental rejection and lack of warmth are somewhat less consistent. Methodological shortcomings in the studies mean that these results should be interpreted with caution. Future research should be conducted using observational and experimental design with adolescents from referred, clinical populations to help identify the critical parental processes and clarify the direction of effects

Pest categorisation of Pseudocercospora pini-densiflorae

Following a request from the European Commission, the EFSA Plant Health (PLH) Panel performed a pest categorisation of Pseudocercospora pini-densiflorae, a well-defined and distinguishable fungal species of the family Mycosphaerellaceae. The regulated harmful organism is the anamorph Cercoseptoria pini-densiflorae (synonym Cercospora pini-densiflorae) with the corresponding teleomorph Mycosphaerella gibsonii. P. pini-densiflorae causes a needle blight of Pinus spp. also known as Cercospora blight of pines or Cercospora needle blight. P. pini-densiflorae is reported from sub-Saharan Africa, Central and South America, Asia and Oceania, but not from the EU. The pathogen is regulated in Council Directive 2000/29/EC (Annex IIAI) as a quarantine organism whose introduction into the EU is banned on plants (other than fruit and seeds) and wood of Pinus. The pest could enter the EU via plants for planting and other means (uncleaned seed, cut branches of pine trees, isolated bark, growing media accompanying plants, and mycorrhizal soil inocula). Hosts are widespread in the EU and favourable climatic conditions are present in Mediterranean countries. Pinus halepensis, Pinus nigra, Pinus pinea, Pinus pinaster and Pinus sylvestris are reported to be highly susceptible to the pathogen. The pest would be able to spread following establishment after introduction in the EU mainly on infected plants for planting. The pest introduction could have impacts in nurseries and young plantations. Cleaning seeds from needles and removing infected seedlings and pine litter from affected nurseries can reduce the risk of establishment in nurseries and of spread from nurseries to forests, especially given the limited scale of splash dispersal. The main knowledge gaps concern (i) the role of means of entry/spread other than plants for planting and (ii) the potential consequences in mature tree plantations and forests. The criteria assessed by the Panel for consideration as potential quarantine pest are met. For regulated nonquarantine pests, the criterion on the pest presence in the EU is not met

Photodynamic Therapy of Tumors Can Lead to Development of Systemic Antigen-Specific Immune Response

Background: The mechanism by which the immune system can effectively recognize and destroy tumors is dependent on recognition of tumor antigens. The molecular identity of a number of these antigens has recently been identified and several immunotherapies have explored them as targets. Photodynamic therapy (PDT) is an anti-cancer modality that uses a non-toxic photosensitizer and visible light to produce cytotoxic reactive oxygen species that destroy tumors. PDT has been shown to lead to local destruction of tumors as well as to induction of anti-tumor immune response. Methodology/Principal Findings: We used a pair of equally lethal BALB/c colon adenocarcinomas, CT26 wild-type (CT26WT) and CT26.CL25 that expressed a tumor antigen, β-galactosidase (β-gal), and we treated them with vascular PDT. All mice bearing antigen-positive, but not antigen-negative tumors were cured and resistant to rechallenge. T lymphocytes isolated from cured mice were able to specifically lyse antigen positive cells and recognize the epitope derived from beta-galactosidase antigen. PDT was capable of destroying distant, untreated, established, antigen-expressing tumors in 70% of the mice. The remaining 30% escaped destruction due to loss of expression of tumor antigen. The PDT anti-tumor effects were completely abrogated in the absence of the adaptive immune response. Conclusion: Understanding the role of antigen-expression in PDT immune response may allow application of PDT in metastatic as well as localized disease. To the best of our knowledge, this is the first time that PDT has been shown to lead to systemic, antigen- specific anti-tumor immunity.United States. National Cancer Institute (grant RO1CA/AI838801)United States. National Cancer Institute (grant R01AI050875

MAGE I Transcription Factors Regulate KAP1 and KRAB Domain Zinc Finger Transcription Factor Mediated Gene Repression

Class I MAGE proteins (MAGE I) are normally expressed only in developing germ cells but are aberrantly expressed in many cancers. They have been shown to promote tumor survival, aggressive growth, and chemoresistance but the underlying mechanisms and MAGE I functions have not been fully elucidated. KRAB domain zinc finger transcription factors (KZNFs) are the largest group of vertebrate transcription factors and regulate neoplastic transformation, tumor suppression, cellular proliferation, and apoptosis. KZNFs bind the KAP1 protein and direct KAP1 to specific DNA sequences where it suppresses gene expression by inducing localized heterochromatin characterized by histone 3 lysine 9 trimethylation (H3me3K9). Discovery that MAGE I proteins also bind to KAP1 prompted us to investigate whether MAGE I can affect KZNF and KAP1 mediated gene regulation. We found that expression of MAGE I proteins, MAGE-A3 or MAGE-C2, relieved repression of a reporter gene by ZNF382, a KZNF with tumor suppressor activity. ChIP of MAGE I (-) HEK293T cells showed KAP1 and H3me3K9 are normally bound to the ID1 gene, a target of ZNF382, but that binding is greatly reduced in the presence of MAGE I proteins. MAGE I expression relieved KAP1 mediated ID1 repression, causing increased expression of ID1 mRNA and ID1 chromatin relaxation characterized by loss of H3me3K9. MAGE I binding to KAP1 also induced ZNF382 poly-ubiquitination and degradation, consistent with loss of ZNF382 leading to decreased KAP1 binding to ID1. In contrast, MAGE I expression caused increased KAP1 binding to Ki67, another KAP1 target gene, with increased H3me3K9 and decreased Ki67 mRNA expression. Since KZNFs are required to direct KAP1 to specific genes, these results show that MAGE I proteins can differentially regulate members of the KZNF family and KAP1 mediated gene repression