Study of heat transfer processes in the flowing part of hypersonic air-ramjet engine

The technique and results of the experimental-theoretical study of gas dynamics, heat transfer and the structure of gas flow in the flowing channel of a model hypersonic air-ramjet engine are presented for Mach numbers M (5; 6)

RIP4 inhibits STAT3 signaling to sustain lung adenocarcinoma differentiation.

Loss of epithelial differentiation and extracellular matrix (ECM) remodeling are known to facilitate cancer progression and are associated with poor prognosis in patients with lung cancer. We have identified Receptor-interacting serine/threonine protein kinase 4 (RIP4) as a regulator of tumor differentiation in lung adenocarcinoma (AC). Bioinformatics analyses of human lung AC samples showed that poorly differentiated tumors express low levels of RIP4, whereas high levels are associated with better overall survival. In vitro, lung tumor cells expressing reduced RIP4 levels showed enhanced activation of STAT3 signaling and had a greater ability to invade through collagen. In contrast, overexpression of RIP4 inhibited STAT3 activation, which abrogated interleukin-6-dependent induction of lysyl oxidase, a collagen cross-linking enzyme. In an autochthonous mouse model of lung AC initiated by Kras(G12D) expression with loss of p53, Rip4 knockdown tumors progressed to a poorly differentiated state marked by an increase in Hmga2, reduced Ttf1, and enrichment of genes regulating extracellular remodeling and Jak-Stat signaling. Tail vein injections of cells overexpressing Rip4 showed a reduced potential to invade and form tumors, which was restored by co-expression of Stat3. Altogether, our work has identified that loss of RIP4 enhances STAT3 signaling in lung cancer cells, promoting the expression of ECM remodeling genes and cancer dedifferentiation

Scleroderma and related disorders: 223. Long Term Outcome in a Contemporary Systemic Sclerosis Cohort

Background: We have previously compared outcome in two groups of systemic sclerosis (SSc) patients with disease onset a decade apart and we reported data on 5 year survival and cumulative incidence of organ disease in a contemporary SSc cohort. The present study examines longer term outcome in an additional cohort of SSc followed for 10 years. Methods: We have examined patients with disease onset between years 1995 and 1999 allowing for at least 10 years of follow-up in a group that has characteristics representative for the patients we see in contemporary clinical practice. Results: Of the 398 patients included in the study, 252 (63.3%) had limited cutaneous (lc) SSc and 146 (36.7%) had diffuse cutaneous (dc) SSc. The proportion of male patients was higher among the dcSSc group (17.1% v 9.9%, p = 0.037) while the mean age of onset was significantly higher among lcSSc patients (50 ± 13 v 46 ± 13 years ± SD, p = 0.003). During a 10 year follow-up from disease onset, 45% of the dcSSc and 21% of the lcSSc subjects developed clinically significant pulmonary fibrosis, p < 0.001. Among them approximately half reached the endpoint within the first 3 years (23% of dcSSc and 10% of lcSSc) and over three quarters within the first 5 years (34% and 16% respectively). There was a similar incidence of pulmonary hypertension (PH) in the two subsets with a steady rate of increase over time. At 10 years 13% of dcSSc and 15% of lcSSc subjects had developed PH (p=0.558), with the earliest cases observed within the first 2 years of disease. Comparison between subjects who developed PH in the first and second 5 years from disease onset demonstrated no difference in demographic or clinical characteristics, but 5-year survival from PH onset was better among those who developed this complication later in their disease (49% v 24%), with a strong trend towards statistical significance (p = 0.058). Incidence of SSc renal crisis (SRC) was significantly higher among the dcSSc patients (12% v 4% in lcSSc, p = 0.002). As previously observed, the rate of development of SRC was highest in the first 3 years of disease- 10% in dcSSc and 3% in lcSSc. All incidences of clinically important cardiac disease developed in the first 5 years from disease onset (7% in dcSSc v 1% in lcSSc, p < 0.001) and remained unchanged at 10 years. As expected, 10-year survival among lcSSc subjects was significantly higher (81%) compared to that of dcSSc patients (70%, p = 0.006). Interestingly, although over the first 5 years the death rate was much higher in the dcSSc cohort (16% v 6% in lcSSc), over the following years it became very similar for both subsets (14% and 13% between years 5 and 10, and 18% and 17% between years 10 and 15 for dcSSc and lcSSc respectively). Conclusions: Even though dcSSc patients have higher incidence for most organ complications compared to lcSSc subjects, the worse survival among them is mainly due to higher early mortality rate. Mortality rate after first 5 years of disease becomes comparable in the two disease subsets. Disclosure statement: The authors have declared no conflicts of interes

Effect of Vitamin D on Peripheral Blood Mononuclear Cells from Patients with Psoriasis Vulgaris and Psoriatic Arthritis

<div><p>Background</p><p>Psoriasis, a chronic skin disease with or without joint inflammation, has increased circulating proinflammatory cytokine levels. Vitamin D is involved in calcium homeostasis, bone formation, osteoclastogenesis and osteoclast activity, as well as regulation of immune response. We aimed to study osteoclast differentiation and cytokine secretion of peripheral blood mononuclear cells (PBMCs) from patients with psoriasis vulgaris and psoriatic arthritis, in response to 1,25(OH)₂D₃.</p><p>Methods</p><p>Serum levels of bone turnover markers were measured by ELISA in patients with psoriasis vulgaris and psoriatic arthritis, and healthy controls. PBMCs were isolated and cultured with or without RANKL/M-CSF and 1,25(OH)₂D₃. Osteoclast differentiation and cytokine secretion were assessed.</p><p>Results</p><p>Psoriatic arthritis patients had lower osteocalcin, as well as higher C-telopeptide of type I collagen and cathepsin K serum levels compared with psoriasis vulgaris patients and controls. RANKL/M-CSF-stimulated PBMCs from psoriatic arthritis patients produced higher proinflammatory cytokine levels and had a differential secretion profile in response to 1,25(OH)₂D₃, compared with psoriasis vulgaris and control PBMCs.</p><p>Conclusions</p><p>Our data confirmed altered bone turnover in psoriatic arthritis patients, and demonstrated increased osteoclastogenic potential and proinflammatory cytokine secretion capacity of these PBMCs compared with psoriasis vulgaris and controls. 1,25(OH)₂D₃ abrogated these effects.</p></div

Bone turnover markers in serum from psoriasis patients and controls.

<p>Box and whisker plots show serum concentrations of A) CTX-1, B) OCN, C) CTX-1/OCN ratio, D) CTX-2, E) CTSK, and F) CTX-1/CTSK ratio in healthy controls (HC, n = 14), and patients with psoriasis vulgaris (PsV, n = 8) and psoriatic arthritis (PsA, n = 11) measured by ELISA kits. Box and whisker plots represent median with minimum to maximum values. *<i>P</i><0.05, **<i>P</i><0.01 and ***<i>P</i><0.001 indicate statistically significant differences obtained by one-way ANOVA with Dunnetts’s multiple comparison test; and #<i>P</i><0.05 only by t-test.</p

Effect of 1,25(OH)₂D₃ on cytokine secretion from PBMCs of psoriasis patients and controls.

<p>PBMCs from healthy controls (HC, white), and patients with psoriasis vulgaris (PsV, light grey) and psoriatic arthritis (PsA, dark grey) were cultured with or without RANKL/M-CSF (RM), and in the presence or in the absence of 1,25(OH)₂D₃ (Vit D). After 14 days supernatant concentrations of A) TNF-α, B) IL-1b, C) IFN-γ, D) IL-17, E) IL-23, F) IL-2, G) RANTES and H) IL-10 were measured by Q-Plex multiplex arrays. Columns represent mean ± SD of fold change of cytokine secretion compared to cytokine levels under culture conditions in the absence of RM and/or Vit D represented by dotted lines. HC, n = 5; PsV, n = 7; and PsA, n = 5; where n is the number of participants. Significant differences were obtained by two way ANOVA followed by Bonferroni post hoc test. *<i>P</i><0.05, **<i>P</i><0.01 and ***<i>P</i><0.001 are statistical significant differences obtained by the Bonferroni post hoc test. #<i>P</i><0.05, ##<i>P</i><0.01 and ###<i>P</i><0.001 indicate statistical significant differences only obtained by Mann-Whitney test.</p

Levels of 1,25(OH)₂D₃, calcium and calcitonin in serum from psoriasis patients and controls.

<p>Box and whisker plots show serum concentrations of A) 1,25(OH)₂D₃, B) calcium and C) calcitonin, in healthy controls (HC, n = 14), and patients with psoriasis vulgaris (PsV, n = 8) and psoriatic arthritis (PsA, n = 11) measured by ELISA kits. Box and whisker plots represent median with minimum to maximum values.</p

Spearman coefficient correlation analysis of serum parameters in healthy controls and patients with psoriasis vulgaris and psoriatic arthritis.

<p>Spearman coefficient correlation analysis of serum parameters in healthy controls and patients with psoriasis vulgaris and psoriatic arthritis.</p