610 research outputs found

    An experimental and theoretical investigation of particle–wall impacts in a T-junction

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    Understanding the behaviour of particles entrained in a fluid flow upon changes in flow direction is crucial in problems where particle inertia is important, such as the erosion process in pipe bends.We present results on the impact of particles in a T-shaped channel in the laminar-turbulent transitional regime. The impacting event for a given system is described in terms of the Reynolds number and the particle Stokes number. Experimental results for the impact are compared with the trajectories predicted by theoretical particle tracing models for a range of configurations to determine the role of the viscous boundary layer in retarding the particles and reducing the rate of collision with the substrate. In particular a 2D model based on a stagnation point flow is used together with 3D numerical simulations. We show how the simple 2D model provides a tractable way of understanding the general collision behaviour, while more advanced 3D simulation can be helpful in understanding the details of the flow

    A mouse model of systemic lupus erythematosus responds better to soluble TACI than to soluble BAFFR, correlating with depletion of plasma cells.

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    The TNF family cytokines B-cell activating factor (BAFF) and a proliferation-inducing ligand (APRIL) support plasma cell survival. It is known that inhibitors of BAFF only (BAFFR-Fc) or BAFF and APRIL (TACI-Fc) administered early enough in an NZB/NZW F1 mouse model of systemic lupus erythematosus (SLE) ameliorate clinical outcomes, pointing to a pathogenic role of BAFF. In the present study, TACI-Fc administrated at a later stage of disease, after onset of autoimmunity, decreased the number of bone marrow plasma cells and slowed down further formation of autoantibodies. TACI-Fc prevented renal damage during a 12-week treatment period regardless of autoantibody levels, while BAFFR-Fc did not despite a similar BAFF-blocking activity in vivo. TACI-Fc also decreased established plasma cells in a T-dependent hapten/carrier immunization system better than single inhibitors of BAFF or APRIL, and sometimes better than combined single inhibitors with at least equivalent BAFF and APRIL inhibitory activities. These results indicate that TACI-Fc can prevent symptoms of renal damage in a mouse model of SLE when BAFFR-Fc cannot, and point to a plasticity of plasma cells for survival factors. Targeting plasma cells with TACI-Fc might be beneficial to prevent autoantibody-mediated damages in SLE

    Inhibition of Membrane-Bound BAFF by the Anti-BAFF Antibody Belimumab.

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    B cell activating factor of the TNF family (BAFF, also known as BLyS), a cytokine that regulates homeostasis of peripheral B cells, is elevated in the circulation of patients with autoimmune diseases such as systemic lupus erythematosus (SLE). BAFF is synthetized as a membrane-bound protein that can be processed to a soluble form after cleavage at a furin consensus sequence, a site that in principle can be recognized by any of the several proteases of the pro-protein convertase family. Belimumab is a human antibody approved for the treatment of SLE, often cited as specific for the soluble form of BAFF. Here we show in different experimental systems, including in a monocytic cell line (U937) that naturally expresses BAFF, that belimumab binds to membrane-bound BAFF with similar EC50 as the positive control atacicept, which is a decoy receptor for both BAFF and the related cytokine APRIL (a proliferation inducing ligand). In U937 cells, binding of both reagents was only detectable in furin-deficient U937 cells, showing that furin is the main BAFF processing protease in these cells. In CHO cells expressing membrane-bound BAFF lacking the stalk region, belimumab inhibited the activity of membrane-bound BAFF less efficiently than atacicept, while in furin-deficient U937 cells, belimumab inhibited membrane-bound BAFF and residual soluble BAFF as efficiently as atacicept. These reagents did not activate complement or antibody-dependent cell cytotoxicity upon binding to membrane-bound BAFF in vitro. In conclusion, our data show that belimumab can inhibit membrane-bound BAFF, and that BAFF in U937 cells is processed by furin

    Comparison of accuracy of single crowns generated from digital and conventional impressions: An in vivo controlled trial

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    Aim With the advances of digital technology, intraoral digital impression (DI) technique has become a major trend in prosthodontics with respect to traditional impression (TI) techniques; despite that, very few data are available concerning its accuracy. Thus, the purpose of this study was to compare the effectiveness of DI versus TI considering both marginal and internal gap (MG, IG, respectively) in cobalt-chromium (Co-Cr) single crowns manufactured by mean of computer-aided design and computer-aided manufacturing (CAD/CAM) technology. Material and methods Thirty posterior teeth were considered for this study. For each abutment tooth, sixty and thirty copings were produced with the aid of TI and DI, respectively. Thirty of the sixty copings of the TI-group were then randomly selected to be veneered and cemented onto existing abutments. The space existing between the internal surface of the coping and the abutment tooth was evaluated onto an in vitro replica; the MG and IG were measured by Scanning Electron Microscope. The data were analysed by the Wilcoxon test (1-tailed). Results The mean MG was 75.04 μm (SD = 13.12) and 55.01 μm (SD = 7.01) for the TI group and DI group, respectively. As regards the mean IGs, the values recorded were of 78.36 μm (SD = 19.66) for the TI-group and 59.20 μm (SD=3.33) for the DI-group. A statistically significant difference was found between the two groups (p-value = 0.001). Conclusions Copings manufactured from DI showed better MGs and IGs with respect to copings produced from TI. However, both approaches produced clinically acceptable results

    Validation of a gold standard method for iodine quantification in raw and processed milk, and its variation in different dairy species

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    Adequate milk consumption significantly contributes to meeting the human iodine recommended daily intake, which ranges from 70 µg/d for infants to 200 µg/d for lactating women. The fulfilment of iodine recommended daily intake is fundamental to prevent serious clinical diseases such as cretinism in infants and goiter in adults. In the present study iodine content was measured in raw and processed commercial cow milk, as well as in raw buffalo, goat, sheep, and donkey milk. Iodine extraction was based on 0.6% (vol/vol) ammonia, whereas iodine detection and quantification were carried out through an inductively coupled plasma mass spectrometer analyzer. Among processed commercial cow milk, partially skimmed pasteurized milk had the greatest iodine content (359.42 µg/kg) and raw milk the lowest (166.92 µg/kg). With regard to the other dairy species, the greatest iodine content was found in raw goat milk (575.42 µg/kg), followed by raw buffalo (229.82 µg/kg), sheep (192.64 µg/kg), and donkey milk (7.06 µg/kg). Repeatability of milk iodine content, calculated as relative standard deviation of 5 measurements within a day or operator, ranged from 0.96 to 1.84% and 0.72 to 1.16%, respectively. The overall reproducibility of milk iodine content, calculated as relative standard deviation of 45 measurements across 3 d of analyses and 3 operators, was 4.01%. These results underline the precision of the proposed analytical method for the determination of iodine content in milk

    Optimising DNA binding to carbon nanotubes by non-covalent methods

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    The use of carbon nanotubes as a gene delivery system has been extensively studied in recent years owing to its potential advantages over viral vectors. To achieve this goal, carbon nanotubes have to be functionalized to become compatible with aqueous media and to bind the genetic material. To establish the best conditions for plasmid DNA binding, we compare the dispersion properties of single-, double- and multi-walled carbon nanotubes (SWCNTs, DWCNTs and MWCNTs, respectively) functionalized with a variety of surfactants by non-covalent attachment. The DNA binding properties of the functionalized carbon nanotubes were studied and compared by electrophoresis. Furthermore, a bilayer functionalization method for DNA binding on SWCNTs was developed that utilized RNA-wrapping to solubilize the nanotubes and cationic polymers as a bridge between nanotubes and DNA

    Fabrication of gradient hydrogels using a thermophoretic approach in microfluidics

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    The extracellular matrix presents spatially varying physical cues that can influence cell behavior in many processes. Physical gradients within hydrogels that mimic the heterogenous mechanical microenvironment are useful to study the impact of these cues on cellular responses. Therefore, simple and reliable techniques to create such gradient hydrogels are highly desirable. This work demonstrates the fabrication of stiffness gradient Gellan gum (GG) hydrogels by applying a temperature gradient across a microchannel containing hydrogel precursor solution. Thermophoretic migration of components within the precursor solution generates a concentration gradient that mirrors the temperature gradient profile, which translates into mechanical gradients upon crosslinking. Using this technique, GG hydrogels with stiffness gradients ranging from 20 to 90 kPa over 600 µm are created, covering the elastic moduli typical of moderately hard to hard tissues. MC3T3 osteoblast cells are then cultured on these gradient substrates, which exhibit preferential migration and enhanced osteogenic potential toward the stiffest region on the gradient. Overall, the thermophoretic approach provides a non-toxic and effective method to create hydrogels with defined mechanical gradients at the micron scale suitable for in vitro biological studies and potentially tissue engineering applications

    Fabrication of gradient hydrogels using a thermophoretic approach in microfluidics

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    The extracellular matrix presents spatially varying physical cues that can influence cell behavior in many processes. Physical gradients within hydrogels that mimic the heterogenous mechanical microenvironment are useful to study the impact of these cues on cellular responses. Therefore, simple and reliable techniques to create such gradient hydrogels are highly desirable. This work demonstrates the fabrication of stiffness gradient Gellan gum (GG) hydrogels by applying a temperature gradient across a microchannel containing hydrogel precursor solution. Thermophoretic migration of components within the precursor solution generates a concentration gradient that mirrors the temperature gradient profile, which translates into mechanical gradients upon crosslinking. Using this technique, GG hydrogels with stiffness gradients ranging from 20 to 90 kPa over 600 µm are created, covering the elastic moduli typical of moderately hard to hard tissues. MC3T3 osteoblast cells are then cultured on these gradient substrates, which exhibit preferential migration and enhanced osteogenic potential toward the stiffest region on the gradient. Overall, the thermophoretic approach provides a non-toxic and effective method to create hydrogels with defined mechanical gradients at the micron scale suitable for in vitro biological studies and potentially tissue engineering applications
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