Differential Metabotypes in Synovial Fibroblasts and Synovial Fluid in Hip Osteoarthritis Patients Support Inflammatory Responses

Changes in cellular metabolism have been implicated in mediating the activated fibroblast phenotype in a number of chronic inflammatory disorders, including pulmonary fibrosis, renal disease and rheumatoid arthritis. The aim of this study was therefore to characterise the metabolic profile of synovial joint fluid and synovial fibroblasts under both basal and inflammatory conditions in a cohort of obese and normal-weight hip OA patients. Furthermore, we sought to ascertain whether modulation of a metabolic pathway in OA synovial fibroblasts could alter their inflammatory activity. Synovium and synovial fluid was obtained from hip OA patients, who were either of normal-weight or obese and were undergoing elective joint replacement surgery. The synovial fluid metabolome was determined by 1H NMR spectroscopy. The metabolic profile of isolated synovial fibroblasts in vitro was characterised by lactate secretion, oxygen consumption rate (OCR) and extracellular acidification rate (ECAR) using the Seahorse XF Analyser. The effects of a small molecule pharmacological inhibitor and siRNA targeted at glutaminase-1 (GLS1) were assessed to probe the role of glutamine metabolism in OA synovial fibroblast function. Obese OA patient synovial fluid (n = 5) exhibited a different metabotype, compared to normal-weight patient fluid (n = 6), with significantly increased levels of 1, 3-dimethylurate, N-Nitrosodimethylamine, succinate, tyrosine, pyruvate, glucose, glycine and lactate, and enrichment of the glutamine–glutamate metabolic pathway, which correlated with increasing adiposity. In vitro, isolated obese OA fibroblasts exhibited greater basal lactate secretion and aerobic glycolysis, and increased mitochondrial respiration when stimulated with pro-inflammatory cytokine TNFα, compared to fibroblasts from normal-weight patients. Inhibition of GLS1 attenuated the TNFα-induced expression and secretion of IL-6 in OA synovial fibroblasts. These findings suggest that altered cellular metabolism underpins the inflammatory phenotype of OA fibroblasts, and that targeted inhibition of glutamine–glutamate metabolism may provide a route to reducing the pathological effects of joint inflammation in OA patients who are obese.     

Intrusion Detection Systems of ICMPv6-based DDoS attacks

Neural Computing and Applications - Denial of Service (DoS) and Distributed Denial of Service (DDoS) attacks are thorny and a grave problem of today’s Internet, resulting in economic damages...     

Adolescents' perceptions of family functioning in the United Arab Emirates

A sample of 710 subjects between 14 and 19 years of age were examined to assess psychological health of United Arab Emirates (UAE) families with adolescent members. The Family Functioning Questionnaire (FFQ) based upon the adolescent's perception of his or her family life and climate contains seven dimensions that constitute the family functioning process: family structure, emotional fulfillment, internal relations, behavioral control, value transmission, basic requirements, and external relations. Results indicate that the adolescents perceived their families to be operating more toward the functional than dysfunctional end of the scale. Males scored their families more functional in family structure and in external relations more significantly than did females. Females perceived their families as more functioning in internal relations, behavioral control, and basic requirements. However, a trend was found in favor of males on emotional fulfillment. Family functioning scores were higher in upper social economic status (SES) families than in other SES levels.     

Frequency and temperature dependence of ac electrical properties of graphitized carbon-black filled rubbers

The a.c. electrical properties of graphitized carbon-black filled rubbers were investigated in the temperature range 25–85°C and in the frequency range 10–10⁶ Hz. The volume fraction of the filler varied from 15 to 60%. The a.c. impedance was found to decrease dramatically with increasing filler content for volume fractions higher than 30%. A relaxation transition with an activation energy of 26·4–50 kJ/mol was observed only in the samples containing 45% and 60% of the fillers. ©1997 SCI     

Investigation of ohmic contact to P-type CdTe:P using ac and dc techniques

The effect of ohmic contact to P-type CdTe:P single crystal has been studied for different back contacts: Au and graphite doped with Cu, Te and CdCl₂. The ac electrical measurements were performed at room temperature in the frequency range 10⁻¹ Hz to 10⁶ Hz. The results were compared with dc measurements at the same temperature. Al/CdTe:P Schottky diodes were fabricated using thermal evaporation technique. The same applies for Au back contacts while for the others, Cu, Te and CdCl₂, powder forms were mixed in fixed portions with graphite. In ac and dc measurements, it was found that Cu electrodes give the lowest contact resistance which is nearly frequency independent in a frequency range 10⁻¹ Hz to about 10³ Hz. However, the plot of the imaginary component (Z″) versus the real component (Z′) of the complex ac impedance yields two semi-circles in the case Cu and Te back contacts with less defined two semi-circles in the case of CdCl₂. For Au back contact a single semi-circle was constructed with a single relaxation time in the order of 0.04 ms. The two semi-circles correspond to the bulk material (imperfections) at high frequency region, and the electrode interface between CdTe:P and the contact electrode. This may indicate that a P⁺ layer has been formed in the interface between the material and the back-contact layer. However, a good correlation was found between the ac and dc measurements for all back contacts.     

Experimental and theoretical investigation of global and diffuse solar radiation in the United Arab Emirates

In the present study, the global, direct and diffuse components of solar radiation as well as temperature, relative humidity and wind speed have been continuously monitored and analysed on an hourly, daily and monthly basis. The monthly average daily total solar radiation varies from 2700 W h/m² in December to 8000 W h/m² in June with an average clearness index of 0.65. Experimental data are compared to the predictions of different theoretical models as functions of declination and hour angles. Correlations are obtained describing the variation of hourly, daily and monthly averages of total and diffuse solar radiation using polynomial expressions. Empirical correlations describing the dependence of the daily average diffuse to total radiation ratio on the clearness index are also obtained. Data for the daily diffuse to total radiation ratio are compared to correlations obtained by other investigators. The comparison shows a reasonable agreement with some scatter due to the seasonal dependence of the correlation. Comparison of calculations with experimental measurements under clear sky conditions show excellent agreement with a maximum error of 8%.