169 research outputs found

    A dataset of tracer concentrations and meteorological observations from the Bolzano Tracer EXperiment (BTEX) to characterize pollutant dispersion processes in an Alpine valley

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    Abstract. The paper describes the dataset of concentrations and related meteorological measurements collected during the field campaign of the Bolzano Tracer Experiment (BTEX). The experiment was performed to characterize the dispersion of pollutants emitted from a waste incinerator in the basin of the city of Bolzano, in the Italian Alps. As part of the experiment, two controlled releases of a passive gas tracer (sulfur hexafluoride, SF6) were performed through the stack of the incinerator on 14 February 2017 for two different time lags, starting, respectively, at 07:00 and 12:45 LST. Samples of ambient air were collected at target sites with vacuum-filled glass bottles and polyvinyl fluoride bags, and they were later analyzed by means of a mass spectrometer (detectability limit 30 pptv). Meteorological conditions were monitored by a network of 15 surface weather stations, 1 microwave temperature profiler, 1 sodar and 1 Doppler wind lidar. The dataset represents one of the few examples available in the literature concerning dispersion processes in a typical mountain valley environment, and it provides a useful benchmark for testing atmospheric dispersion models in complex terrain. The dataset described in this paper is available at https://doi.org/10.1594/PANGAEA.898761 (Falocchi et al., 2019)

    Hologene 5: A Phase II/III Clinical Trial of Combined Cell and Gene Therapy of Junctional Epidermolysis Bullosa

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    Epidermolysis bullosa (EB) is a group of devastating genetic diseases characterized by skin and mucosal fragility and formation of blisters, which develop either spontaneously or in response to minor mechanical trauma. There is no definitive therapy for any form of EB. Intermediate junctional EB (JEB) caused by mutations in the gene LAMB3 has been the first genetic skin disease successfully tackled by ex vivo gene therapy. Here, we present a multicenter, open-label, uncontrolled phase II/III study that aims at confirming the efficacy of Hologene 5, a graft consisting of cultured transgenic keratinocytes and epidermal stem cells and meant to combine cell and gene therapy for the treatment of LAMB3-related JEB. Autologous clonogenic keratinocytes will be isolated from patients’ skin biopsies, genetically corrected with a gamma-retroviral vector (γRV) carrying the full-length human LAMB3 cDNA and plated onto a fibrin support (144cm2). The transgenic epidermis will be transplanted onto surgically prepared selected skin areas of at least six JEB patients (four pediatric and two adults). Evaluation of clinical efficacy will include, as primary endpoint, a combination of clinical parameters, such as percentage of re-epithelialization, cellular, molecular, and functional parameters, mechanical stress tests, and patient-reported outcome (PRO), up to 12months after transplantation. Safety and further efficacy endpoints will also be assessed during the clinical trial and for additional 15years in an interventional non-pharmacological follow-up study. If successful, this clinical trial would provide a therapeutic option for skin lesions of JEB patients with LAMB3 mutations and pave the way to a combined cell and gene therapy platform tackling other forms of EB and different genodermatoses. Clinical Trial Registration: EudraCT Number: 2018-000261-36

    Effort angina in a patient with advanced coronary artery disease. Role played by coronary angiography, Ivus and cardiac CT: case report

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    Coronary angiography is considered to be the gold standard technique for assessing the severity of obstructive luminal narrowing; however, in a few circumstances it may be misleading. In these cases, cardiac computed tomography (CT) and intravascular ultrasound (IVUS) may help to give a correct interpretation

    Characterization of ten highly polymorphic microsatellite loci for the intertidal mussel Perna perna, and cross species amplification within the genus

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    The brown mussel Perna perna (Linnaeus, 1758) is a dominant constituent of intertidal communities and a strong invader with multiple non-native populations distributed around the world. In a previous study, two polymorphic microsatellite loci were developed and used to determine population-level genetic diversity in invasive and native P. perna populations. However, higher number of microsatellite markers are required for reliable population genetic studies. In this context, in order to understand P. perna origins and history of invasion and to compare population genetic structure in native versus invaded areas, we developed 10 polymorphic microsatellite markers. Findings Described microsatellite markers were developed from an enriched genomic library. Analyses and characterization of loci using 20 individuals from a population in Western Sahara revealed on average 11 alleles per locus (range: 5–27) and mean gene diversity of 0.75 (range: 0.31 - 0.95). One primer pair revealed possible linkage disequilibrium while heterozygote deficiency was significant at four loci. Six of these markers cross-amplified in P. canaliculus (origin: New Zealand). Conclusions Developed markers will be useful in addressing a variety of questions concerning P. perna, including dispersal scales, genetic variation and population structure, in both native and invaded areas.Peer Reviewe

    Purification of Human Plasma/Cellular Fibronectin and Fibronectin Fragments

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    A method is described for the purification of plasma fibronectins based on a combination of gelatin- and arginine-Sepharose chromatography steps. Cellular fibronectin can be purified from an osteosarcoma fibroblast cell line by affinity chromatography using a monoclonal antibody anti-fibronectin as ligand. Furthermore, we also provide a protocol for the purification of fibronectin domains obtained by fractionation of thermolysin-digested plasma fibronectin on ion-exchange/gel filtration chromatography columns. Assessment of the fibronectin purity is performed by SDS-PAGE, while the ligand binding activities of specific fibronectin domains are determined by ELISA

    Pancreatitis after percutaneous ethanol injection into HCC: a minireview of the literature

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    Deaths after percutaneous ethanol injection (PEI) into hepatocellular carcinoma (HCC) may occur within a few hours to a few days following the procedure because of hemoperitoneum and haemorrhage from oesophageal varices or hepatic insufficiency. Pancreatitis has been recently reported as a rare lethal complication of intra-arterial PEI, another modality for treating HCCs. In this minireview, we analyze the literature concerning the development of acute pancreatitis after PEI. Pathogenesis of pancreatitis from opioids and ethanol is also addressed. Treatment with opioids to reduce the patient's abdominal pain after PEI in combination with the PEI itself may lead to direct toxic effects, thus favouring the development of pancreatitis

    Characterisation and radioimmunotherapy of L19-SIP, an anti-angiogenic antibody against the extra domain B of fibronectin, in colorectal tumour models

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    Angiogenesis is a characteristic feature of tumours and other disorders. The human monoclonal antibody L19- SIP targets the extra domain B of fibronectin, a marker of angiogenesis expressed in a range of tumours. The aim of this study was to investigate whole body distribution, tumour localisation and the potential of radioimmunotherapy with the L19-small immunoprotein (SIP) in colorectal tumours. Two colorectal tumour models with highly different morphologies, the SW1222 and LS174T xenografts, were used in this study. Localisation and retention of the L19-SIP antibody at tumour vessels was demonstrated using immunohistochemistry and Cy3-labelled L19-SIP. Whole body biodistribution studies in both tumour models were carried out with 125I-labelled L19-SIP. Finally, 131I-labelled antibody was used to investigate the potential of radioimmunotherapy in SW1222 tumours. Using immunohistochemistry, we confirmed extra domain B expression in the tumour vasculature. Immunofluorescence demonstrated localisation and retention of injected Cy3-labelled L19-SIP at the abluminal side of tumour vessels. Biodistribution studies using a 125I-labelled antibody showed selective tumour uptake in both models. Higher recorded values for localisation were found in the SW1222 tumours than in the LS174T (7.9 vs 6.6 %ID g−1), with comparable blood clearance for both models. Based on these results, a radioimmunotherapy study was performed in the SW1222 xenograft using 131I-Labelled L19-SIP (55.5 MBq), which showed selective tumour uptake, tumour growth inhibition and improved survival. Radio- and fluorescence-labelled L19-SIP showed selective localisation and retention at vessels of two colorectal xenografts. Furthermore, 131I-L19-SIP shows potential as a novel treatment of colorectal tumours, and provides the foundation to investigate combined therapies in the same tumour models

    Evidence for rangewide panmixia despite multiple barriers to dispersal in a marine mussel

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    Oceanographic features shape the distributional and genetic patterns of marine species by interrupting or promoting connections among populations. Although general patterns commonly arise, distributional ranges and genetic structure are species-specific and do not always comply with the expected trends. By applying a multimarker genetic approach combined with Lagrangian particle simulations (LPS) we tested the hypothesis that oceanographic features along northeastern Atlantic and Mediterranean shores influence dispersal potential and genetic structure of the intertidal mussel Perna perna. Additionally, by performing environmental niche modelling we assessed the potential and realized niche of P. perna along its entire native distributional range and the environmental factors that best explain its realized distribution. Perna perna showed evidence of panmixia across > 4,000 km despite several oceanographic breaking points detected by LPS. This is probably the result of a combination of life history traits, continuous habitat availability and stepping-stone dynamics. Moreover, the niche modelling framework depicted minimum sea surface temperatures (SST) as the major factor shaping P. perna distributional range limits along its native areas. Forthcoming warming SST is expected to further change these limits and allow the species to expand its range polewards though this may be accompanied by retreat from warmer areas.Fundacao para a Ciencia e Tecnologia (FCT-MEC, Portugal) [UID/Multi/04326/2013, IF/01413/2014/CP1217/CT0004]; South African Research Chairs Initiative (SARChI) of the Department of Science and Technology; National Research Foundation; South African National Research Foundation (NRF); Portuguese Fundacao para a Ciencia e Tecnologia (FCT) [SFRH/BPD/85040/2012, SFRH/BPD/111003/2015]info:eu-repo/semantics/publishedVersio

    Cytotoxic targeting of F9 teratocarcinoma tumours with anti-ED-B fibronectin scFv antibody modified liposomes

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    We prepared small unilamellar liposomes derivatised with single chain antibody fragments specific for the ED-B domain of B-fibronectin. This extracellular matrix associated protein is expressed around newly forming blood vessels in the vicinity of many types of tumours. The single chain antibody fragments were functionalised by introduction of C-terminal cysteines and linked to liposomes via maleimide groups located at the terminal ends of poly(ethylene glycol) modified phospholipids. The properties of these anti-ED-B single chain antibody fragments-liposomes were analysed in vitro on ED-B fibronectin expressing Caco-2 cells and in vivo by studying their biodistribution and their therapeutic potential in mice bearing subcutanous F9 teratocarcinoma tumours. Radioactively labelled (114mIndium) single chain antibody fragments-liposomes accumulated in the tumours at 2–3-fold higher concentrations during the first 2 h after i.v. injection compared to unmodified liposomes. After 6–24 h both liposome types were found in similar amounts (8–10% injected dose g−1) in the tumours. Animals treated i.v. with single chain antibody fragments-liposomes containing the new cytotoxic agent 2′-deoxy-5-fluorouridylyl-N4-octadecyl-1-β-D-arabinofuranosylcytosine (30 mg kg-1 per dose, five times every 24 h) showed a reduction of tumour growth by 62–90% determined on days 5 and 8, respectively, compared to animals receiving control liposomes. Histological analysis revealed a marked reduction of F9 tumour cells and excessive deposition of fibronectin in the extracellular matrix after treatment with single chain antibody fragments-2-dioxy-5-fluorouridylyl-N4-octadecyl-1-β-D-arabinofuranosylcytosine-liposomes. Single chain antibody fragments-liposomes targeted to ED-B fibronectin positive tumours therefore represent a promising and versatile novel drug delivery system for the treatment of tumours
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