Aggrecan, the major proteoglycan of cartilage that provides its mechanical properties of compressibility and elasticity, is one of the first matrix components to undergo measurable loss in arthritic diseases. bond, this protease cleaves at four sites within the chondroitin-sulfate rich region of the aggrecan core protein, between G2 and G3 globular domains. Importantly, we show that this cleavage occurs more efficiently than cleavage within the IGD at the Glu 373 -Ala 374 bond. Cleavage occurred preferentially at the KEEE 1667-1668 GLGS bond to produce both a 140-kDa COOH-terminal fragment and a 375-kDa fragment that retains an intact G1. Cleavage also occurred at the GELE 1480 -1481 GRGT bond to produce a 55-kDa COOH-terminal fragment and a G1-containing fragment of 320 kDa. Cleavage of this 320-kDa fragment within the IGD at the Glu 373 -Ala 374 bond then occurred to release the 250-kDa BC-3-reactive fragment from the G1 domain. The 140-kDa GLGS-reactive fragment resulting from the preferential cleavage was further processed at two additional cleavage sites, at TAQE 1771 -1772 AGEG and at VSQE [1871][1872] LGQR resulting in the formation of a 98-kDa fragment with an intact G3 domain and two small fragments of ϳ20 kDa. These data elucidate the sites and efficiency of cleavage during aggrecan degradation by aggrecanase and suggest potential tools for monitoring aggrecan cleavage in arthritis.Aggrecan is the major proteoglycan of cartilage and provides this tissue with its mechanical properties of compressibility and elasticity. Aggrecan monomers interact with hyaluronan and are usually found as part of a large aggregate containing 10 -100 monomers per hyaluronan molecule. The primary role of aggrecan is to swell and hydrate the framework of cartilage collagen fibrils thus providing cartilage with its properties of compressibility and elasticity. The NH 2 terminus of the aggrecan monomer core protein is comprised of two globular domains called G1 and G2 that are separated by an interglobular domain (IGD) 1 that spans about 150 residues in length. The G2 region is followed by a long central glycosaminoglycan (GAG) attachment region and by a COOH-terminal globular domain, G3 (2, 3).In cartilage degradation associated with diseases such as osteoarthritis and rheumatoid arthritis, aggrecan is one of the first matrix components to undergo measurable loss that ultimately leads to a loss of cartilage function. Proteolytic cleavage within the IGD is believed to be responsible for the loss of aggrecan from cartilage. Two major sites of proteolytic cleavage have been identified within the IGD, one between amino acids Asn 341 and Phe 342 and the other between Glu 373 and Ala 374 . Matrix metalloproteinases, including MMP
Background The Democratic Republic of the Congo (DRC) organized a first mass distribution campaign of long-lasting insecticidal nets (LLINs) with digitalized data management with coordinated support from the Ministry of Health (MOH) and Santé Pour Tous En Milieu Rural—an ‘Association sans but lucratif’ (SANRU Asbl), in the context of the Covid-19 pandemic in Kongo Central province. This article describes the planning and implementation process of this campaign as well as the challenges and lessons learned. Methods The planning and implementation process was performed in line with the standard guidance issued by the National Malaria Control Programme (NMCP) following the start of Covid-19. The changes and adaptations put in place as well as the challenges encountered are described. Results A total of 5,629,211 people were registered (7.7% above projection) in 1,065,537 households (6.2% below projection) giving an average of 5.3 people per household. Of a total of 3,062,850 LLINs ordered, 2,886,096 were distributed to households (94%). Out of 11,070 villages and 3,947 teams planned, 91.7% of villages were reached and 93% of teams were established. Conclusion The revision of standards of campaign implementation during Covid-19, as well as effective coordination supported by real-time decision-making through digital data management, have been factors in the success of this campaign. Maintaining this momentum is essential to ensure the continuity of malaria prevention services for the population.
A methodology is presented for assessing internal flow-induced vibrations (FIV) in subsea piping systems. Finite Element (FE) models are constructed for the subject piping systems, including insulation, internal hydrocarbon weight and added mass of the surrounding sea water. Operating vibration data are measured using ROV-deployable accelerometer loggers clamped directly to the piping systems. The measured data are processed, analyzed and used for two purposes: model verification and dynamic response correlation. Modal parameters are extracted from the measured data and compared to the modal parameters computed from the structural FE model. The model is refined until the frequencies and mode shape errors are within the desired tolerance. The measured data are then used to derive a representative forcing function for use with frequency-domain random response analysis. The forcing function is derived such that the properties of the predicted vibration spectrum match those of the measured vibration spectrum for all measurement locations. The method presented herein provides a novel semi-empirical technique for calibrating FE models to make fatigue life predictions for subsea piping systems using measured vibration data.
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