254 research outputs found

    Treatment efficiency and membrane fouling of a lab-scale anaerobic membrane bioreactor treating dilute municipal wastewater

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    The study aims to investigate the application of anaerobic processes coupled with membrane filtration for treating dilute municipal wastewater in Hanoi city

    Thyroid hormone receptor expression during metamorphosis of Atlantic halibut (Hippoglossus hippoglossus)

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    Flatfish such as the Atlantic halibut (Hippoglossus hippoglossus) undergo a dramatic metamorphosis that transforms the pelagic, symmetric larva into a benthic, cranially asymmetric juvenile. In common with amphibian metamorphosis, flatfish metamorphosis is under endocrine control with thyroid hormones being particularly important. In this report we confirm that tri-iodothyronine (T3) levels peak at metamorphic climax during halibut metamorphosis. Moreover we have isolated cDNA clones of TR and TR genes and confirmed the presence in halibut of two TR isoforms (representing the products of distinct genes) and two TR isoforms (generated from a single gene by alternative splicing). Real time PCR was used to assess expression of these genes during metamorphosis. TR shows the most dramatic expression profile, with a peak occurring during metamorphic climax.This work has been carried out within the project “Arrested development: The Molecular and Endocrine Basis of Flatfish Metamorphosis” (Q5RS-2002-01192) with financial support from the Commission of the European Communities. However, it does not necessarily reflect the Commission’s views and in no way anticipates its future policy in this area. We thank Heiddis Smáradóttir (Fiskeldi Eyjafjarðar, IS-600 Akureyri, Iceland) for collecting and providing the Atlantic halibut samples, and Karin Pittman and Øystein Sæle (both from the Department of Biology, University of Bergen, Norway) for analysing samples to determine developmental stage. We are also grateful to Marco Campinho for preparing the RNA used in the study

    High ALDH Activity Identifies Chemotherapy-Resistant Ewing's Sarcoma Stem Cells That Retain Sensitivity to EWS-FLI1 Inhibition

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    Cancer stem cells are a chemotherapy-resistant population capable of self-renewal and of regenerating the bulk tumor, thereby causing relapse and patient death. Ewing's sarcoma, the second most common form of bone tumor in adolescents and young adults, follows a clinical pattern consistent with the Cancer Stem Cell model - remission is easily achieved, even for patients with metastatic disease, but relapse remains frequent and is usually fatal.We have isolated a subpopulation of Ewing's sarcoma cells, from both human cell lines and human xenografts grown in immune deficient mice, which express high aldehyde dehydrogenase (ALDH(high)) activity and are enriched for clonogenicity, sphere-formation, and tumor initiation. The ALDH(high) cells are resistant to chemotherapy in vitro, but this can be overcome by the ATP binding cassette transport protein inhibitor, verapamil. Importantly, these cells are not resistant to YK-4-279, a small molecule inhibitor of EWS-FLI1 that is selectively toxic to Ewing's sarcoma cells both in vitro and in vivo.Ewing's sarcoma contains an ALDH(high) stem-like population of chemotherapy-resistant cells that retain sensitivity to EWS-FLI1 inhibition. Inhibiting the EWS-FLI1 oncoprotein may prove to be an effective means of improving patient outcomes by targeting Ewing's sarcoma stem cells that survive standard chemotherapy

    Studies in Dhāraṇī Literature II: Pragmatics of Dhāraṇīs

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    This article is one of a series that reassesses the dhāraṇī texts of Mahāyāna Buddhism. The article seeks to examine dhāraṇī texts by using the linguistic tools of pragmatics, especially historical pragmatics, to assist the understanding of their statements. Rather than the meaning of the term dhāraṇī as a subject term, the domain of truth-conditional semantics, this paper examines statements in texts labelled dhāraṇī. Pragmatics examines meaning in context, and the categories of speech acts developed by Searle has been especially helpful in mapping out differences within such texts and the formalization of statements across texts. The grammaticalization of specific speech elements, especially interjections, in the context of mantra-dhāraṇīs is also discussed

    Efficacy and pharmacokinetic/pharmacodynamic evaluation of the Aurora kinase A inhibitor MLN8237 against preclinical models of pediatric cancer

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    To gain a greater understanding of the potential of the Aurora kinase A inhibitor MLN8237 in the treatment of pediatric malignancies. The activity of MLN8237 was evaluated against 28 neuroblastoma and Ewing sarcoma cell lines, and its in vivo efficacy was studied over a range of doses against 12 pediatric tumor xenograft models. Pharmacokinetic, pharmacodynamic, and genomic studies were undertaken. In vitro neuroblastoma cell lines were generally more sensitive to MLN8237 than Ewing sarcoma lines. MLN8237 demonstrated significant activity in vivo against solid tumor models at the maximum tolerated dose (MTD); however, only 2 of 6 neuroblastoma models had objective responses at 0.25MTD. In contrast, MLN8237 induced objective responses at its MTD and at 0.5MTD in three ALL models and in two out of three at 0.25MTD. Pharmacokinetic studies at 0.5MTD demonstrated a T (max) of 0.5 h, C (max) of 24.8 mu M, AUC((0-24)) of 60.3 mu M h, and 12 h trough level of 1.2 mu M. Mitotic indices increased 6-12 h after MLN8237 administration. AURKA copy number variation was frequent in xenografts, and expression was highly correlated with copy number. Objective responses were more frequent in tumors with decreased AURKA copy number (5/8) compared to those with increased gene copy number (2/14). This report confirms the significant activity against both solid tumor and ALL xenografts at the MTD, with a steep dose response. These data support clinical development of MLN8237 in childhood cancer. Because of the steep dose-response relationship, such studies should target achieving trough levels of 1 mu M or higher for sustained periods of treatment

    Non-classical forms of pemphigus: pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus

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    The pemphigus group comprises the autoimmune intraepidermal blistering diseases classically divided into two major types: pemphigus vulgaris and pemphigus foliaceous. Pemphigus herpetiformis, IgA pemphigus, paraneoplastic pemphigus and IgG/IgA pemphigus are rarer forms that present some clinical, histological and immunopathological characteristics that are different from the classical types. These are reviewed in this article. Future research may help definitively to locate the position of these forms in the pemphigus group, especially with regard to pemphigus herpetiformis and the IgG/ IgA pemphigus.Universidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Dermatology DepartmentUniversidade Federal de São Paulo (UNIFESP), Escola Paulista de Medicina (EPM) Dermatology and Pathology DepartmentsUNIFESP, EPM, Dermatology DepartmentUNIFESP, EPM, Dermatology and Pathology DepartmentsSciEL
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