1,016 research outputs found

    Rotor For A Hover-Capable Aircraft And Method For Containment Of Vibrations Transmitted To The Mast Of A Rotor Of A Hover-Capable Aircraft

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    A rotor (3) for a hover-capable aircraft is described, comprising: a hub (5) rotatable about an axis (A) and, in turn, comprising a plurality of blades (9); a mast (6) connectable to a drive member of the aircraft (1) and operatively connected to the hub (5) to drive the hub (5) in rotation about the axis (A); and damping means (15) for damping vibrations transmitted to the mast (6), which comprise a mass (17) designed to oscillate in a plane transversal to the axis (A) so as to contain flexural vibrations of the mast (6) generated by rotation of the blades (9); the damping means (15) also comprise elastic means (30) having a desired stiffness along the axis (A) and operatively connected to the mass (17) to contain vibration of the mast (6) along the axis (A)

    Latanoprost ophthalmic solution in the treatment of open angle glaucoma or raised intraocular pressure: a review

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    Latanoprost is a prostaglandin F2-alpha isopropyl ester prodrug which is rapidly hydrolyzed by esterases in the cornea to the biologically active latanoprost acid. When latanoprost is topically administered into the eye, the cornea seems to act like as a slow-release depot to the anterior segment. One hour after administration maximum concentration is found in the iris, followed by the anterior chamber and the ciliary body. Despite extensive research, controversy remains about the real mechanism of action of this drug. Immunohistochemical data have shown that the intraocular pressure (IOP) reduction with topical prostaglandin F2-alpha is associated with a reduction of collagens within the uveoscleral outflow pathway. Evidence from several experimental and clinical studies suggests that latanoprost is a valuable addition first-line treatment alternatives for glaucoma, ocular hypertension and even angle-closure glaucoma. Strong points are its efficacy, which is demonstrated to be higher than that of brimonidine, dorzolamide and timolol with fewer systemic adverse effects; a convenient administration schedule; and the IOP-controlling pattern, which is relatively flat compared with timolol and dorzolamide, and enables better control in glaucoma progression, since large fluctuations may be associated with the risk of developing glaucoma in untreated ocular hypertensive subjects

    miR-146a controls CXCR4 expression in a pathway that involves PLZF and can be used to inhibit HIV-1 infection of CD4+ T lymphocytes

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    Abstract MicroRNA miR-146a and PLZF are reported as major players in the control of hematopoiesis, immune function and cancer. PLZF is described as a miR-146a repressor, whereas CXCR4 and TRAF6 were identified as miR-146a direct targets in different cell types. CXCR4 is a co-receptor of CD4 molecule that facilitates HIV-1 entry into T lymphocytes and myeloid cells, whereas TRAF6 is involved in immune response. Thus, the role of miR-146a in HIV-1 infection is currently being thoroughly investigated. In this study, we found that PLZF mediates suppression of miR-146a to control increases of CXCR4 and TRAF6 protein levels in human primary CD4 + T lymphocytes. We show that miR-146a upregulation by AMD3100 treatment or PLZF silencing, decreases CXCR4 protein expression and prevents HIV-1 infection of leukemic monocytic cell line and CD4 + T lymphocytes. Our findings improve the prospects of developing new therapeutic strategies to prevent HIV-1 entry via CXCR4 by using the PLZF/miR-146a axis

    Assessment of a Vision-Based Technique for an Automatic Van Herick Measurement System

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    The adoption of artificial intelligence (AI) methods within the instrumentation and measurements field is nowadays an attractive research area. On the one hand, making machines learn from data how to perform an activity, rather than hard code sequential instructions, is a convenient and effective solution in many modern research areas. On the other hand, AI allows for the compensation of inaccurate or not complete models of specific phenomena or systems. In this context, this article investigates the possibility to exploit suitable machine learning (ML) techniques in a vision-based ophthalmic instrument to perform automatic anterior chamber angle (ACA) measurements. In particular, two convolutional neural network (CNN)-based networks have been identified to automatically classify acquired images and select the ones suitable for the Van Herick procedure. Extensive clinical trials have been conducted by clinicians, from which a realistic and heterogeneous image dataset has been collected. The measurement accuracy of the proposed instrument is derived by extracting measures from the images of the aforementioned dataset, as well as the system performances have been assessed with respect to differences in patients' eye color. Currently, the ACA measurement procedure is performed manually by appropriately trained medical personnel. For this reason, ML and vision-based techniques may greatly improve both test objectiveness and diagnostic accessibility, by enabling an automatic measurement procedure

    Entry inhibition of HSV-1 and -2 protects mice from viral lethal challenge

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    The present study focused on inhibition of HSV-1 and -2 replication and pathogenesis in vitro and in vivo, through the selective targeting of the envelope glycoprotein D. Firstly, a human monoclonal antibody (Hu-mAb#33) was identified that could neutralise both HSV-1 and -2 at nM concentrations, including clinical isolates from patients affected by different clinical manifestations and featuring different susceptibility to acyclovir in vitro. Secondly, the potency of inhibition of both infection by cell-free viruses and cell-to-cell virus transmission was also assessed. Finally, mice receiving a single systemic injection of Hu-mAb#33 were protected from death and severe clinical manifestations following both ocular and vaginal HSV-1 and -2 lethal challenge. These results pave the way for further studies reassessing the importance of HSV entry as a novel target for therapeutic intervention and inhibition of cell-to-cell virus transmission

    Quantum dots labelling allows detection of the homing of mesenchymal stem cells administered as immunomodulatory therapy in an experimental model of pancreatic islets transplantation

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    Cell transplantation is considered a promising therapeutic approach in several pathologies but still needs innovative and non-invasive imaging technologies to be validated. The use of mesenchymal stem cells (MSCs) attracts major interest in clinical transplantation thanks to their regenerative properties, low immunogenicity and ability to regulate immune responses. In several animal models, MSCs are used in co-transplantation with pancreatic islets (PIs) for the treatment of type I diabetes, supporting graft survival and prolonging normal glycaemia levels. In this study we investigated the homing of systemically administered MSCs in a rat model of pancreatic portal vein transplantation. MSCs labelled with quantum dots (Qdots) were systemically injected by tail vein and monitored by optical fluorescence imaging. The fluorescence signal of the liver in animals co-transplanted with MSCs and PIs was significantly higher than in control animals in which MSCs alone were transplanted. By using magnetic labelling of PIs, the homing of PIs into liver was independently confirmed. These results demonstrate that MSCs injected in peripheral blood vessels preferentially accumulate into liver when PIs are transplanted in the same organ. Moreover, we prove that bimodal MRI-fluorescence imaging allows specific monitoring of the fate of two types of cells

    Hematopoietic reconstitution dynamics of mobilized- and bone marrow-derived human hematopoietic stem cells after gene therapy

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    Mobilized peripheral blood is increasingly used instead of bone marrow as a source of autologous hematopoietic stem/progenitor cells for ex vivo gene therapy. Here, we present an unplanned exploratory analysis evaluating the hematopoietic reconstitution kinetics, engraftment and clonality in 13 pediatric Wiskott-Aldrich syndrome patients treated with autologous lentiviral-vector transduced hematopoietic stem/progenitor cells derived from mobilized peripheral blood (n = 7), bone marrow (n = 5) or the combination of the two sources (n = 1). 8 out of 13 gene therapy patients were enrolled in an open-label, non-randomized, phase 1/2 clinical study (NCT01515462) and the remaining 5 patients were treated under expanded access programs. Although mobilized peripheral blood- and bone marrow- hematopoietic stem/progenitor cells display similar capability of being gene-corrected, maintaining the engineered grafts up to 3 years after gene therapy, mobilized peripheral blood-gene therapy group shows faster neutrophil and platelet recovery, higher number of engrafted clones and increased gene correction in the myeloid lineage which correlate with higher amount of primitive and myeloid progenitors contained in hematopoietic stem/progenitor cells derived from mobilized peripheral blood. In vitro differentiation and transplantation studies in mice confirm that primitive hematopoietic stem/progenitor cells from both sources have comparable engraftment and multilineage differentiation potential. Altogether, our analyses reveal that the differential behavior after gene therapy of hematopoietic stem/progenitor cells derived from either bone marrow or mobilized peripheral blood is mainly due to the distinct cell composition rather than functional differences of the infused cell products, providing new frames of references for clinical interpretation of hematopoietic stem/progenitor cell transplantation outcome.</p

    Liver function following hepatitis C virus eradication by direct acting antivirals in patients with liver cirrhosis: data from the PITER cohort

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    Background: The development of direct-acting antivirals (DAA) for HCV has revolutionized the treatment of HCV, including its treatment in patients with HIV coinfection. The aim of this study was to compare the changes in liver function between coinfected and monoinfected patients with cirrhosis who achieved HCV eradication by DAA. Methods: Patients with pre-treatment diagnosis of HCV liver cirrhosis, consecutively enrolled in the multicenter PITER cohort, who achieved a sustained virological response 12 weeks after treatment cessation (SVR12) were analysed. Changes in Child-Pugh (C-P) class and the occurrence of a decompensating event was prospectively evaluated after the end of DAA treatment. Cox regression analysis was used to evaluate factors independently associated with changes in liver function following viral eradication. Results: We evaluated 1350 patients, of whom 1242 HCV monoinfected (median follow-up 24.7, range 6.8–47.5 months after viral eradication) and 108 (8%) HCV/HIV coinfected (median follow-up 27.1, range 6.0–44.6). After adjusting for age, sex, HCV-genotype, HBsAg positivity and alcohol use, HIV was independently associated with a more advanced liver disease before treatment (C-P class B/C vs A) (OR: 3.73, 95% CI:2.00–6.98). Following HCV eradication, C-P class improved in 17/20 (85%) coinfected patients (from B to A and from C to B) and in 53/82 (64.6%) monoinfected patients (from B to A) (p = 0.08). C-P class worsened in 3/56 coinfected (5.3%) (from A to B) and in 84/1024 (8.2%) monoinfected patients (p = 0.45) (from A to B or C and from B to C). Baseline factors independently associated with C-P class worsening were male sex (HR = 2.00; 95% CI = 1.18–3.36), platelet count &lt; 100,000/μl (HR = 1.75; 95% CI 1.08–2.85) and increased INR (HR = 2.41; 95% CI 1.51–3.84). Following viral eradication, in 7 of 15 coinfected (46.6%) and in 61 of 133 (45.8%) monoinfected patients with previous history of decompensation, a new decompensating event occurred. A first decompensating event was recorded in 4 of 93 (4.3%) coinfected and in 53 of 1109 (4.8%) monoinfected patients (p =&nbsp;0.83). Conclusions: Improvement of liver function was observed following HCV eradication in the majority of patients with cirrhosis; however viral eradication did not always mean cure of liver disease in both monoinfected and coinfected patients with advanced liver disease
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