214 research outputs found
Thermal and Acoustic Characterization of Innovative and Unconventional Panels Made of Reused Materials
Europe calls for a transition to the circular economy model based on recycling, reuse, the
proper design of products, and repair. Recycling requires energy and chemical products for waste
processing; on the contrary, reusing reduces the impact of transportation and expands the life of
materials that cannot be recycled. This article highlights the characteristics of selected end-of-life
materials; it aims to raise awareness among manufacturers to consider products’ conscious design
to facilitate their reuse in different sectors. Panels 7 cm thick, realized by assembling cardboard
packaging, egg boxes, bulk polyester, and felt, have been experimentally tested to understand whether
they can be installed indoors to improve thermal and acoustic comfort. The panels’ equivalent thermal
conductivity λeq measured through the guarded hot plate method is 0.071 W/m K. Acoustic tests
have been performed in a sound transmission room and a reverberation room. The weighted
sound reduction index Rw is 19 dB, the weighted sound absorption coefficient αw is 0.30, and the
noise reduction coefficient NRC is 0.64. The measured properties have been compared to those
of commercial materials, and the results show that the panels have interesting properties from
the thermal and acoustic points of view. They could be employed in the building sector and in
disadvantaged contexts where low-income people cannot afford commercial insulating materials.
Although other factors, such as fire resistance, need to be evaluated, these results show that the
proposed approach is feasible
Chimneys in wooden roofs: a 3D steady numerical model for the prediction of the temperatures
Chimneys convey exhaust gas produced in domestic heat appliances to the external environment and to do this they have to pass
through floors and roofs: if these elements are made up of flammable materials, the fire hazard may occur. This article presents
the verification of a 3D numerical model set for the determination of the stationary temperatures reached on the flammable
materials in the vicinity of chimneys. The verification has been done comparing the temperatures measured in experimental
tests with those estimated by means of the numerical model. Results show that the 3D numerical model is a valid tool for the
analysis of heat transfer between chimney and roof. Since in the experimental tests it is not always possible to reach stationary
temperatures, a lumped element model to estimate them is also proposed and it could support the chimney certification
The antibody-mediated targeted delivery of interleukin-10 inhibits endometriosis in a syngeneic mouse model
BACKGROUND Endometriosis is still a highly underdiagnosed disease, and the current medical and surgical treatment of endometriosis is associated with a high recurrence rate. This study investigates the use of derivatives of the human antibody F8, specific to the alternatively spliced extra-domain A of fibronectin (Fn), for the imaging and treatment of endometriosis. METHODS Immunohistochemistry and immunofluorescence was used to evaluate antigen expression in endometriotic tissue of human endometriosis and of a syngeneic mouse model of the disease. The in vivo targeting performance of a fluorescent derivative of the F8 antibody was assessed by imaging mice with endometriosis using a near-infrared fluorescence imager, 24 h following i.v. injection of the antibody conjugate. Furthermore, the mouse model was used for therapy experiments using two recombinant F8-based immunocytokines [F8-interleukin-10 (IL10) and F8-IL2] or saline for the treatment groups. RESULTS A very strong vascular expression of splice isoforms of Fn and of tenascin-C was observed in human endometriotic lesions by immunohistochemistry and immunofluorescence techniques. After i.v. administration, a selective accumulation of the F8 antibody in endometriotic lesions could be observed in a syngeneic mouse model. These targeting data were used as a basis for therapy experiments with a pro-inflammatory (F8-IL2) and an anti-inflammatory (F8-IL10) cytokine fusion protein of the F8 antibody. The average lesion size in the F8-IL10 treatment group was clearly reduced compared with the saline control group and with the F8-IL2 group, for which no therapeutic effects were observed. CONCLUSIONS The F8 antibody targets endometriotic lesions in vivo in a mouse model of endometriosis and may be used for the non-invasive imaging of the disease and for the pharmacodelivery of anti-inflammatory cytokines, such as IL1
Preclinical characterization of DEKAVIL (F8-IL10), a novel clinical-stage immunocytokine which inhibits the progression of collagen-induced arthritis
Introduction
In this article, we present a comparative immunohistochemical evaluation of four clinical-stage antibodies (L19, F16, G11 and F8) directed against splice isoforms of fibronectin and of tenascin-C for their ability to stain synovial tissue alterations in rheumatoid arthritis patients. Furthermore we have evaluated the therapeutic potential of the most promising antibody, F8, fused to the anti-inflammatory cytokine interleukin (IL) 10.
Methods
F8-IL10 was produced and purified to homogeneity in CHO cells and shown to comprise biological active antibody and cytokine moieties by binding assays on recombinant antigen and by MC/9 cell proliferation assays. We have also characterized the ability of F8-IL10 to inhibit arthritis progression in the collagen-induced arthritis mouse model.
Results
The human antibody F8, specific to the extra-domain A of fibronectin, exhibited the strongest and most homogenous staining pattern in synovial biopsies and was thus selected for the development of a fully human fusion protein with IL10 (F8-IL10, also named DEKAVIL). Following radioiodination, F8-IL10 was able to selectively target arthritic lesions and tumor neo-vascular structures in mice, as evidenced by autoradiographic analysis and quantitative biodistribution studies. The subcutaneous administration route led to equivalent targeting results when compared with intravenous administration and was thus selected for the clinical development of the product. F8-IL10 potently inhibited progression of established arthritis in the collagen-induced mouse model when tested alone and in combination with methotrexate. In preparation for clinical trials in patients with rheumatoid arthritis, F8-IL10 was studied in rodents and in cynomolgus monkeys, revealing an excellent safety profile at doses tenfold higher than the planned starting dose for clinical phase I trials.
Conclusions
Following the encouraging preclinical results presented in this paper, clinical trials with F8-IL10 will now elucidate the therapeutic potential of this product and whether the targeted delivery of IL10 potentiates the anti-arthritic action of the cytokine in rheumatoid arthritis patients.ISSN:1465-9905ISSN:1465-9913ISSN:1478-6362ISSN:1478-635
A general method for the selection of high-level scFv and IgG antibody expression by stably transfected mammalian cells
The isolation of mammalian cell lines capable of high-yield expression of recombinant antibodies is typically performed by screening multiple individual clones by limiting dilution techniques. A number of experimental strategies have recently been devised to identify high-expressing clones, but protocols are often difficult to implement, time consuming, costly and limited in terms of number of clones which can be screened. In this article, we describe new vectors for the expression of recombinant antibodies in IgG format and in other formats, based on the single-chain Fv module, as well as a high-throughput screening procedure, based on the direct staining of antibodies transiting the membrane of a stably transfected cell, followed by preparative sorting using a high-speed cell sorter. This procedure allows, in one step, to deposit single cells into individual wells of a 96-well microtiter plate (thus facilitating cloning) and to preferentially recover those rare cell populations which express dramatically higher levels of recombinant antibody. Using cell cultures followed by affinity purification techniques, we could confirm that the new vectors and the new screening procedure reliably yield high-expression clones and homogenous protein preparations. We expect that these techniques should find broad applicability for both academic and industrial antibody engineering researc
Expression, engineering and characterization of the tumor-targeting heterodimeric immunocytokine F8-IL12
Proinflammatory cytokines have been used for several years in patients with advanced cancer but their administration is typically associated with severe toxicity hampering their application to therapeutically active regimens. This problem can be overcome by using immunocytokines (cytokines fused to antibody or antibody fragments) which selectively deliver the active cytokine to the tumor environment. Preclinical and recent clinical results confirmed that this approach is a very promising avenue to go. We designed an immunocytokine consisting of the scFv(F8) specific to extra-domain A of fibronectin and the very potent human cytokine interleukin-12 (IL12). The heterodimeric nature of IL12 allows the engineering of various immunocytokine formats, based on different combinations of the two subunits (p35 and p40) together with the scFv. In comparison to monomeric or homodimeric cytokines, the construction of a heterodimeric immunocytokine poses many challenges, e.g. gene dosing, stable high-yield expression as well as good manufacture practice (GMP) purification and characterization. In this paper, we describe the successful construction, characterization and production of the heterodimeric immunocytokine F8-IL12. The positive outcome of this feasibility study leads now to GMP production of F8-IL12, which will soon enter clinical trial
Polyamide waste thermal and acoustic properties: experimental and numerical investigation on possible reuse for indoor comfort improvement
Referring to the circular economy model, end-of-life household materials (EoLHM) such as packaging, and clothes, could be converted into building elements – for example panels - with thermal and acoustic properties. Given the high availability almost anywhere, EoLHM represents an alternative to commercial insulating materials that, even though relatively cheap, cannot be afforded by disadvantaged people. The panels are intended for the refurbishment of existing buildings and, therefore, to be installed indoor. This paper presents a multidisciplinary analysis aimed at the characterization of polyamide 6.6 waste from the production of non surgical face masks. The analysis focuses on thermal and acoustic aspects that have determined experimentally by means of the hot plate with guard ring test, and the impedance tube technique respectively. Then, the influence of the panel position on the indoor operative temperature and the reverberation time has been analysed numerically. Results show that, from the thermal and acoustic point of view, this waste is suitable for the realization of building panels and the performance depends on the density and the thickness of the material. However, aspects such as the fire-resistance and the containment of the material need further investigation.Peer ReviewedPostprint (published version
Partial least squares path modelling for the evaluation of patients' satisfaction after thoracic surgical procedures☆
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FT-IR spectroscopy supported by PCA–LDA analysis for the study of embryonic stem cell differentiation
As recently pointed out in the literature, Fourier transform infrared (FT-IR) spectroscopy is emerging as a powerful tool in stem cell research. In this work we characterizedin situby FT-IR microspectroscopy the differentiation of murine embryonic stem cells (ES) to monitor possible changes in the cell macromolecular content during the early stages of differentiation. Undifferentiated and differentiating cells at 4, 7, 9 and 14 days were measured. Data were analyzed by the principal component and subsequent linear discriminant analyses (PCA–LDA) that enabled us to segregate ES cell spectra into well separate clusters and to identify the most significant spectral changes. Important changes in the lipid (3050–2800 cm–1), protein (1700–1600 cm–1) and in the nucleic acid (1050–850 cm–1) absorption regions were observed between days 4 to 7 of differentiation, indicating the appearance – at day 7 – of the new phenotype into cardiomyocyte precursors. Also the presence of DNA/RNA hybrid bands (954 cm–1and 899 cm–1) suggests that the transcriptional switch of the genome started at this stage of differentiation. Particularly noteworthy, we suggest that the 2936 cm–1shoulder we observed could reflect methyl group vibrations thus allowing the detection of variations in methylation levels of the stem cell during differentiation. These infrared results were found to be in agreement with the biochemical characterization of these differentiating cells, underlying the great potential of FT-IR spectroscopy in stem cell research
FT-IR spectroscopy supported by PCA–LDA analysis for the study of embryonic stem cell differentiation
As recently pointed out in the literature, Fourier transform infrared (FT-IR) spectroscopy is emerging as a powerful tool in stem cell research. In this work we characterizedin situby FT-IR microspectroscopy the differentiation of murine embryonic stem cells (ES) to monitor possible changes in the cell macromolecular content during the early stages of differentiation. Undifferentiated and differentiating cells at 4, 7, 9 and 14 days were measured. Data were analyzed by the principal component and subsequent linear discriminant analyses (PCA–LDA) that enabled us to segregate ES cell spectra into well separate clusters and to identify the most significant spectral changes. Important changes in the lipid (3050–2800 cm–1), protein (1700–1600 cm–1) and in the nucleic acid (1050–850 cm–1) absorption regions were observed between days 4 to 7 of differentiation, indicating the appearance – at day 7 – of the new phenotype into cardiomyocyte precursors. Also the presence of DNA/RNA hybrid bands (954 cm–1and 899 cm–1) suggests that the transcriptional switch of the genome started at this stage of differentiation. Particularly noteworthy, we suggest that the 2936 cm–1shoulder we observed could reflect methyl group vibrations thus allowing the detection of variations in methylation levels of the stem cell during differentiation. These infrared results were found to be in agreement with the biochemical characterization of these differentiating cells, underlying the great potential of FT-IR spectroscopy in stem cell research
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