9 research outputs found

    Parametric Modeling as a Technology of Rapid Prototyping in Light Industry

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    The paper deals with the parametric modeling method of virtual mannequins for the purposes of design automation in clothing industry. The described approach includes the steps of generation of the basic model on the ground of the initial one (obtained in 3D-scanning process), its parameterization and deformation. The complex surfaces are presented by the wireframe model. The modeling results are evaluated with the set of similarity factors. Deformed models are compared with their virtual prototypes. The results of modeling are estimated by the standard deviation factor

    Randomized trial of three doses of vitamin D to reduce deficiency in pregnant Mongolian womenResearch in context

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    Background: In winter in Mongolia, 80% of adults have 25-hydroxyvitamin D (25(OH)D) concentrations <25 nmol/l (<10 ng/ml) and 99% have <50 nmol/l (<20 ng/ml). The vitamin D dose to avert deficiency during pregnancy in this population is unknown. Methods: We conducted a randomized, controlled, double-blind trial of daily 600, 2000, or 4000 IU vitamin D3 for pregnant women in Mongolia (Clinicaltrials.gov #NCT02395081). We examined 25(OH)D concentrations at baseline (12–16 weeks' gestation), 36–40 weeks' gestation and in umbilical cord blood, using enzyme linked fluorescent assay. Sample size was determined to detect 0.4 standard deviation differences in 25(OH)D concentrations with 80% power. Findings: 119 pregnant women were assigned 600 IU, 121 assigned 2000 IU and 120 assigned 4000 IU from February 2015 through December 2016. Eighty-eight percent of participants took ≥80% of assigned supplements. At baseline, 25(OH)D concentrations were similar across arms; overall mean ± standard deviation concentration was 19 ± 22 nmol/l; 91% were < 50 nmol/l. At 36–40 weeks, 25(OH)D concentrations increased to 46 ± 21, 70 ± 23, and 81 ± 29 nmol/l for women assigned 600, 2000, and 4000 IU, respectively (p < 0.0001 across arms; p = 0.002 for 2000 vs. 4000 IU). Mean umbilical cord 25(OH)D concentrations differed by study arm (p < 0.0001 across arms; p < 0.0001 for 2000 vs. 4000 IU) and were proportional to maternal concentrations. There were no adverse events, including hypercalcemia, attributable to vitamin D supplementation. Interpretation: Daily supplementation of 4000 IU during pregnancy is safe and achieved higher maternal and neonatal 25(OH)D concentrations than 2000 IU. Daily 600 IU supplements are insufficient to prevent vitamin D deficiency in Mongolia. Fund: Anonymous foundation and Brigham and Women's Hospital. Keywords: Vitamin D deficiency, Trial, Pregnancy, Dosin

    Vitamin D supplements and prevention of tuberculosis infection and disease

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    BACKGROUND: Vitamin D metabolites support innate immune responses to Mycobacterium tuberculosis. METHODS: We randomly assigned children who had negative results for Mycobacterium tuberculosis infection, using the QuantiFERON-TB Gold In-tube assay (QFT), to receive a weekly oral dose of 14,000 IU vitamin D3 or placebo over 3 years. The primary outcome was the proportion of children having a positive QFT result at 3 years. Secondary outcomes included end-study vitamin D status and incidence of tuberculosis disease, acute respiratory infections and adverse events. RESULTS: 8851 participants underwent randomization (4418 to vitamin D, 4433 to placebo), of whom 95.6% had baseline serum 25-hydroxyvitamin D concentrations <20 ng/mL. Mean end-study 25-hydroxyvitamin D concentration in participants randomized to vitamin D vs. placebo was 31.0 vs. 10.7 ng/mL (95% CI for difference, 19.9 to 20.6 ng/mL), and 147 participants in the vitamin D group vs. 134 participants in the placebo group tested positive by QFT (adjusted risk ratio [aRR] 1.10, 95% CI 0.87 to 1.38, P=0.42). Tuberculosis disease was diagnosed in 21 children in the vitamin D group and 25 children in the placebo group (aRR 0.87, 95% CI 0.49 to 1.55). 29 participants randomized to vitamin D and 34 randomized to placebo were hospitalized for treatment of acute respiratory infections (aRR 0.86, 95% CI 0.52 to 1.40). Incidence of adverse events did not differ significantly between study arms. CONCLUSIONS: Vitamin D supplementation did not reduce risk of tuberculosis infection, tuberculosis disease or acute respiratory infections among vitamin D-deficient schoolchildren in Mongolia

    eNAMPT/TLR4 inflammatory cascade activation is a key contributor to SLE Lung vasculitis and alveolar hemorrhage

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    Rationale: Effective therapies to reduce the severity and high mortality of pulmonary vasculitis and diffuse alveolar hemorrhage (DAH) in patients with systemic lupus erythematosus (SLE) is a serious unmet need. We explored whether biologic neutralization of eNAMPT (extracellular nicotinamide phosphoribosyl-transferase), a novel DAMP and Toll-like receptor 4 ligand, represents a viable therapeutic strategy in lupus vasculitis. Methods: Serum was collected from SLE subjects (n = 37) for eNAMPT protein measurements. In the preclinical pristane-induced murine model of lung vasculitis/hemorrhage, C57BL/6 J mice (n = 5–10/group) were treated with PBS, IgG (1 mg/kg), or the eNAMPT-neutralizing ALT-100 mAb (1 mg/kg, IP or subcutaneously (SQ). Lung injury evaluation (Day 10) included histology/immuno-histochemistry, BAL protein/cellularity, tissue biochemistry, RNA sequencing, and plasma biomarker assessment. Results: SLE subjects showed highly significant increases in blood NAMPT mRNA expression and eNAMPT protein levels compared to healthy controls. Preclinical pristane-exposed mice studies showed significantly increased NAMPT lung tissue expression and increased plasma eNAMPT levels accompanied by marked increases in alveolar hemorrhage and lung inflammation (BAL protein, PMNs, activated monocytes). In contrast, ALT-100 mAb-treated mice showed significant attenuation of inflammatory lung injury, alveolar hemorrhage, BAL protein, tissue leukocytes, and plasma inflammatory cytokines (eNAMPT, IL-6, IL-8). Lung RNA sequencing showed pristane-induced activation of inflammatory genes/pathways including NFkB, cytokine/chemokine, IL-1β, and MMP signaling pathways, each rectified in ALT-100 mAb-treated mice. Conclusions: These findings highlight the role of eNAMPT/TLR4-mediated inflammatory signaling in the pathobiology of SLE pulmonary vasculitis and alveolar hemorrhage. Biologic neutralization of this novel DAMP appears to serve as a viable strategy to reduce the severity of SLE lung vasculitis
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