4,576 research outputs found

    Response and optimization of an isolation system with relaxation type damping

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    Response and optimization of isolation system with relaxation type dampin

    Effect of vertical active vibration isolation on tracking performance and on ride qualities

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    An investigation to determine the effect on pilot performance and comfort of an active vibration isolation system for a commercial transport pilot seat is reported. The test setup consisted of: a hydraulic shaker which produced random vertical vibration inputs; the active vibration isolation system; the pilot seat; the pilot control wheel and column; the side-arm controller; and a two-axis compensatory tracking task. The effects of various degrees of pilot isolation on short-term (two-minute) tracking performance and comfort were determined

    IS AGRICULTURAL SECTOR GROWTH A PRECONDITION FOR ECONOMIC GROWTH? THE CASE OF SOUTH AFRICA

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    In this paper a simple growth model is adapted to explain the effect of the agricultural sectors' growth on the non-agricultural sector. The empirical results suggest that for a 1% growth in the agricultural sector, the non-agricultural sector responds by more than 1%. The results also confirm that productivity difference exists, the non-agricultural sector being more efficient in terms of input use. The empirical results support the argument of President T. Mbeki, that South Africa should follow an "agricultural-led" growth strategy for successful development.International Development,

    THE POLITICAL ECONOMY OF FOOD PRICE INFLATION IN SOUTH AFRICA

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    This paper reports on a study that investigated the increase in food prices in South Africa. It is set against the scenario of an increasing inflation rate since September 2001. The June 2002 STATSSA figures estimated the annual inflation rate (CPIX) at 8.8% with food inflation being the major contributor with an annual increase of 14%. The high unemployment and poverty rate in South Africa has already lead to concerns about the negative impact of these increases on the cost of living for the poorest. In this paper we show that the sharp depreciation of the exchange rate towards the end of 2001 had a major impact on the producer price of maize one of the key agricultural commodities because of its role as a staple food and as an input in the production of white and red meat and other animal products.Demand and Price Analysis, Political Economy,

    FREQUENCY, ANGIOGENIC POTENTIAL, PHENOTYPE AND MOLECULAR SIGNATURE OF ENDOTHELIAL COLONY-FORMING CELLS ISOLATED FROM PATIENTS WITH CLASSIC KAPOSI¿S SARCOMA

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    Abstract Background Kaposi\u2019s Sarcoma (KS) is a lymphangioproliferative disease whose causative agent is herpesvirus HHV-8. KS is characterized by hyperproliferation of HHV-8 infected spindle cells - cells of endothelial origin that represent the typical component of KS lesions. In previous studies we reported that circulating endothelial progenitor cells (EPCs), identified as CD45dim/CD34+/KDR+, are increased in patients with classic KS (cKS) and we also demonstrated that in cKS patients EPCs - isolated and cultured as Endothelial colony-forming cells (ECFCs) - are HHV-8 infected and can act as viral reservoir. Therefore, in this study we investigated whether ECFCs isolated from cKS patients are endowed with features typical of spindle cells in order to evaluate whether they may represent the precursors of spindle cells. Moreover, in preliminary studies we surprisingly observed that not only ECFCs isolated from cKS patients but also ECFCs isolated from healthy donors expressed LYVE-1 and podoplanin \u2013 lymphatic markers expressed by spindle cells in KS lesions. Since several studies supported the hypothesis that adult lymphangiogenesis could be promoted by the presence of bone marrow derived lymphatic endothelial progenitor cells (LEPCs) we also investigated the lymphangiogenic potential of ECFCs to evaluate whether they can act also as LEPCs. In particular, we evaluated the expression of lymphatic markers in basal condition and we investigated whether the lymphatic differentiation of ECFCs could be fostered by fibronectin a component of the tumor microenvironment whose presence correlates with tumor lymphangiogenesis and metastasis. In addition, we also evaluated whether migration stimulating factor (MSF), an oncofetal isoform of fibronectin released by cancer stromal cells and tumor associated macrophages, could promote lymphatic differentiation of ECFCs. Methods 83 cKS patients and 86 healthy HHV-8 seronegative donors were enrolled in the study. ECFCs were isolated using a protocol previously optimized in our lab. PBMCs were seeded in EGM-2 medium in culture plates coated with fibronectin and ECFC colonies were identified by microscopic visual inspection as colonies of cells with cobblestone-like morphology. Once isolated, ECFC colonies were expanded in culture plates coated with collagen. During the isolation phase, the time of appearance and the frequency of ECFC colonies were analyzed. During the following expansion phase, ECFC phenotype and the presence of HHV8-infection - assessed as expression of the viral latent nuclear antigen (LANA) - were analyzed by immunofluorescence. ECFC were functionally characterized by evaluating their cell viability, proliferative potential, vasculogenesis ability by Matrigel assay and cytokine production by ELISA. The molecular signature of ECFCs was also analyzed by gene array analysis. To investigate the lymphatic differentiative potential of ECFCs the expression of typical lymphatic markers (PROX-1, podoplanin, LYVE-1 and VEGFR-3) was analyzed by Real Time PCR and confocal microscopy. To evaluate the possible role of fibronectin in promoting lymphatic differentiation, ECFCs were cultured on either fibronectin or collagen and the effects of stimulation with MSF were also analyzed. Results In our study ECFC colonies appeared earlier (p<0.001) and with higher frequency (p<0.001) when isolated from cKS patients than healthy donors. Moreover, the frequency of ECFC colonies was higher in cKS patients with rapidly evolving disease than in cKS patients with slowly evolving disease (p<0.05). All screened ECFC colonies isolated from cKS patients contained HHV8-infected cells. During the expansion phase, ECFCs isolated from cKS patients were endowed with a higher proliferative potential (p<0.05), a higher vasculogenic ability in vitro (p<0.05) and a higher production of IL-6 (p<0.05) than ECFCs isolated from healthy donors. In addition, preliminary analysis of the gene expression profile revealed that patients and healthy controls segregated by clustering, thus confirming that gene expression profile differs between ECFCs isolated from cKS patients and healthy donors. A further relevant result of this study was the observation that ECFCs are endowed with the ability to express the typical lymphatic markers PROX-1, podoplanin, LYVE-1 and VEGFR-3. In particular, lymphatic markers were expressed by donor-derived ECFCs cultured on both fibronectin and collagen and they were upregulated by ECFC treatment with MSF (p<0.05). Conclusion In this study we demonstrated that ECFCs obtained from cKS patients are endowed with features that may be particularly relevant to KS pathogenesis, suggesting that ECFCs may act as putative precursors of the spindle cells and contribute to the development of KS lesions. Moreover, we demonstrated that ECFCs isolated from peripheral blood of adult healthy donors expressed markers typical of lymphatic endothelium, suggesting that ECFCs may act also as LEPCs thus participating in lymphangiogenic and lymphovasculogenic processes

    Bright expression of CD91 identifies highly activated human dendritic cells that can be expanded by defensins

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    CD91 is a scavenger receptor expressed by different immune cells and its ligands defensins have been demonstrated to contribute to immune responses against infections and tumors. We previously demonstrated that CD91 is expressed on human monocyte-derived dendritic cells (moDCs) and that human defensins stimulate in vitro the activation of these cells. In this study, we observed that CD91 is expressed at different levels on two distinct moDC subsets: CD91dim and CD91bright moDCs. Although CD91bright moDCs represented a small proportion of total moDCs, this subset showed higher levels of activation and maturation markers compared to CD91dim moDCs. The frequency of CD91bright moDCs increased by ~50% after in vitro stimulation with recombinant Human Neutrophil Peptide-1 (rHNP-1) and recombinant Human Beta Defensin-1 (rHBD-1), while lipopolysaccharide (LPS) stimulation decreased it by ~35%. Both defensins up-regulated moDC expression of CD80, CD40, CD83 and HLA-DR, although to a lower extent compared with LPS. Notably, upon culture with rHNP-1 and rHBD-1, CD91bright moDCs maintained their higher activation/maturation status, while this was lost upon culture with LPS. Our findings suggest that defensins promote the differentiation into activated CD91bright DCs and may encourage the exploitation of the CD91/defensins axis as a novel therapeutic strategy to potentiate antimicrobial and antitumor immune response

    Concerning the unexpected prothrombotic state following some coronavirus disease 2019 vaccines

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    Currently, the world is coping with the COVID-19 pandemic with a few vaccines. So far, the European Medicine Agency has approved four of them. However, following widespread vaccination with the recombinant adenoviral vector-based Oxford-AstraZeneca vaccine, available only in the United Kingdom and Europe, many concerns have emerged, especially the report of several cases of the otherwise rare cerebral sinus vein thrombosis and splanchnic vein thrombosis. The onset of thrombosis particularly at these unusual sites, about 5–14 days after vaccination, along with thrombocytopenia and other specific blood test abnormalities, are the main features of the vaccine side effects. The acronym vaccine-induced prothrombotic immune thrombocytopenia (VIPIT) has been coined to name this new condition, with the aim of highlighting the difference from the classic heparin-induced thrombocytopenia (HIT). VIPIT seems to primarily affect young to middle-aged women. For this reason, the vaccine administration has been stopped or limited in a few European countries. Coagulopathy induced by the Oxford- AstraZeneca vaccine (and probably by Janssen/Johnson &amp; Johnson vaccine as well in the USA) is likely related to the use of recombinant vector DNA adenovirus, as experimentally proven in animal models. Conversely, Pfizer and Moderna vaccines use mRNA vectors. All vaccineinduced thrombotic events should be treated with a nonheparin anticoagulant. As the condition has some similarities with HIT, patients should not receive any heparin or platelet transfusion, as these treatments may potentially worsen the clinical course. Aspirin has limited rational use in this setting and is not currently recommended. Intravenous immunoglobulins may represent another potential treatment, but, most importantly, clinicians need to be aware of this new unusual postvaccination syndrome

    More favorable metabolic impact of three-times-weekly versus daily growth hormone (GH) treatment in na\uefve GH-deficient children

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    OBJECTIVE: Growth hormone treatment (GHT) is commonly administered daily, although pulsatile GH secretion is unlikely to be achieved. The auxological effect of a three-injections-per-week (TIW) regimen is controversial, while the metabolic effects have been never evaluated in children. The objective was to evaluate whether two different regimens of weekly injections could lead to similar auxological and metabolic effects in children with GH deficiency (GHD). DESIGN: 32 GHD children (25 males, mean age 10.5 \ub1 2.2 yr) were randomly assigned to receive daily (group A, No 16) or TIW (group B, No 16) GHT for 12 months. METHODS: Auxological parameters, insulin-like growth factor-I (IGF-I), glucose and insulin during OGTT, glycosylated hemoglobin (HbA1c), lipid profile, the oral disposition index (DIo), the homeostasis model assessment estimate of insulin resistance (Homa-IR) and the insulin sensitivity index (ISI). RESULTS: After 12 months, both groups showed a significant and comparable improvement in height (p<0.001) and IGF-I (p<0.001). As regards the metabolic parameters, in both groups we found a significant increase in fasting insulin (p<0.001 and p=0.026) and Homa-IR (p<0.001 and p=0.019). A significant increase in fasting glucose (p=0.001) and a decrease in ISI (p<0.001) and DIo (p=0.002) were only found in group A. CONCLUSIONS: The TIW regimen is effective and comparable with the daily regimen in improving auxological parameters and has a more favorable metabolic impact in GHD children (www.ClinicalTrials.gov. NCT03033121)

    SUSCEPTIBILITY MAPPING OF SHALLOW LANDSLIDES INDUCING DEBRIS FLOWS: A COMPARISON OF PHYSICS-BASED APPROACHES

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    The assessment of timing and potential locations of rainfallinduced shallow landslides through mathematical models represents a challenge for the assessment of landslide hazard, especially in cases with limited or not available data. In fact, modeling slope hydrological response and stability requires accurate estimates of unsaturated/saturated hydraulic and geotechnical properties of materials involved in landsliding, as well as climate and topography. Such aspect is relevant for the prediction of location and timing of landslide events, which is greatly needed to reduce their catastrophic effects in terms of economic losses and casualties. To such a scope, we present the comparison of results of two physics-based models applied to the assessment of susceptibility to shallow rainfall-induced landslides in Valtellina region (northern Italy). The analyses were carried out considering effects of availability, resolution and type of data concerning spatial distribution, thickness and properties of soils coverings. For such a scope, the Transient Rainfall Infiltration and Grid-Based Regional Slope-Stability (TRIGRS) and the Climatic Rainfall Hydrogeological Modeling Experiment (CHRyME) models were considered. The study emphasizes issues in performing distributed numerical slope stability modeling depending on the availability of spatially distributed soil properties which hamper the quality of physic-based models. Further analyses aimed at the probabilistic assessment of landslide spatial distribution, related to a specific value of rainfall threshold, can be considered as potentially applicable to multi-scale landslide hazard mapping and extendable to other similar mountainous frameworks

    Costimulatory Molecules and Immune Checkpoints Are Differentially Expressed on Different Subsets of Dendritic Cells

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    Dendritic cells (DCs) play a crucial role in initiating and shaping immune responses. The effects of DCs on adaptive immune responses depend partly on functional specialization of distinct DC subsets, and partly on the activation state of DCs, which is largely dictated by environmental signals. Fully activated immunostimulatory DCs express high levels of costimulatory molecules, produce pro-inflammatory cytokines, and stimulate T cell proliferation, whereas tolerogenic DCs express low levels of costimulatory molecules, produce immunomodulatory cytokines and impair T cell proliferation. Relevant to the increasing use of immune checkpoint blockade in cancer treatment, signals generated from inhibitory checkpoint molecules on DC surface may also contribute to the inhibitory properties of tolerogenic DCs. Yet, our knowledge on the expression of inhibitory molecules on human DC subsets is fragmentary. Therefore, in this study, we investigated the expression of three immune checkpoints on peripheral blood DC subsets, in basal conditions and upon exposure to pro-inflammatory and anti-inflammatory stimuli, by using a flow cytometric panel that allows a direct comparison of the activatory/inhibitory phenotype of DC-lineage and inflammatory DC subsets. We demonstrated that functionally distinct DC subsets are characterized by differential expression of activatory and inhibitory molecules, and that cDC1s in particular are endowed with a unique immune checkpoint repertoire characterized by high TIM-3 expression, scarce PD-L1 expression and lack of ILT2. Notably, this unique cDC1 repertoire was subverted in a group of patients with myelodysplastic syndromes included in the study. Applied to the characterization of DCs in the tumor microenvironment, this panel has the potential to provide valuable information to be used for investigating the role of DC subsets in cancer, guiding DC-targeting treatments, and possibly identifying predictive biomarkers for clinical response to cancer immunotherapy
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