21,704 research outputs found
Control and Filtering for Discrete Linear Repetitive Processes with H infty and ell 2--ell infty Performance
No full textRepetitive processes are characterized by a series of sweeps, termed passes, through a set of dynamics defined over a finite duration known as the pass length. On each pass an output, termed the pass profile, is produced which acts as a forcing function on, and hence contributes to, the dynamics of the next pass profile. This can lead to oscillations which increase in amplitude in the pass to pass direction and cannot be controlled by standard control laws. Here we give new results on the design of physically based control laws for the sub-class of so-called discrete linear repetitive processes which arise in applications areas such as iterative learning control. The main contribution is to show how control law design can be undertaken within the framework of a general robust filtering problem with guaranteed levels of performance. In particular, we develop algorithms for the design of an H? and dynamic output feedback controller and filter which guarantees that the resulting controlled (filtering error) process, respectively, is stable along the pass and has prescribed disturbance attenuation performance as measured by and – norms
Cathepsin K in lymphangioleiomyomatosis: LAM cell-fibroblast Interactions enhance protease activity by extracellular acidification
No full textLymphangioleiomyomatosis (LAM) is a rare disease in which clonal ‘LAM’ cells infiltrate the lungs and lymphatics. In association with recruited fibroblasts, LAM cells form nodules adjacent to lung cysts. It is assumed LAM nodule derived proteases lead to cyst formation although, this is uncertain. We profiled protease gene expression in whole lung tissue and observed cathepsin K was 40 fold over-expressed in LAM compared with control lungs (p≤0.0001). Immunohistochemistry confirmed cathepsin K protein in LAM nodules but not control lungs. Cathepsin K gene expression, protein and protease activity was detected in LAM associated fibroblasts but not the LAM cell line 621-101. In lung nodules, cathepsin K immune reactivity was predominantly co-localised with LAM associated fibroblasts. In vitro, extra-cellular cathepsin K activity was minimal at pH 7.5 but significantly enhanced in fibroblast cultures at pH 7 and 6. 621-101 cells reduced extracellular pH by 0.5 units over 24 hours. Acidification was dependent upon 621-101 cell mTOR activity and net hydrogen ion transporters, particularly sodium/bicarbonate co-transporters and carbonic anhydrases which were also expressed in LAM lung tissue. In LAM cell/fibroblast co-cultures, acidification paralleled cathepsin K activity and both were inhibited by sodium bicarbonate co-transporter (p≤0.0001) and carbonic anhydrase inhibitors (p=0.0021). Our findings suggest cathepsin K activity is dependent on LAM cell/fibroblast interactions and inhibitors of extracellular acidification may be potential therapies for LAM
Cathepsin K in Lymphangioleiomyomatosis: LAM Cell-Fibroblast Interactions Enhance Protease Activity by Extracellular Acidification
No full textCopyright \ua9 2017 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved. Lymphangioleiomyomatosis (LAM) is a rare disease in which LAM cells and fibroblasts form lung nodules and it is hypothesized that LAM nodule-derived proteases cause cyst formation and tissue damage. On protease gene expression profiling in whole lung tissue, cathepsin K gene expression was 40-fold overexpressed in LAM compared with control lung tissue (P ≤ 0.0001). Immunohistochemistry confirmed cathepsin K protein was expressed in LAM but not control lungs. Cathepsin K gene expression and protein and protease activity were detected in LAM-associated fibroblasts but not the LAM cell line 621-101. In lung nodules, cathepsin K immunoreactivity predominantly co-localized with LAM-associated fibroblasts. In vitro, fibroblast extracellular cathepsin K activity was minimal at pH 7.5 but significantly enhanced at pH 7 and 6. 621-101 cells reduced extracellular pH with acidification dependent on 621-101 mechanistic target of rapamycin activity and net hydrogen ion exporters, particularly sodium bicarbonate co-transporters and carbonic anhydrases, which were also expressed in LAM lung tissue. In LAM cell-fibroblast co-cultures, acidification paralleled cathepsin K activity, and both were reduced by sodium bicarbonate co-transporter (P ≤ 0.0001) and carbonic anhydrase inhibitors (P = 0.0021). Our findings suggest that cathepsin K activity is dependent on LAM cell-fibroblast interactions, and inhibitors of extracellular acidification may be potential therapies for LAM
Clinical Utility of a Commercial LAM-ELISA Assay for TB Diagnosis in HIV-Infected Patients Using Urine and Sputum Samples
No full textBackground: The accurate diagnosis of TB in HIV-infected patients, particularly with advanced immunosuppression, is difficult. Recent studies indicate that a lipoarabinomannan (LAM) assay (Clearview-TB (R)-ELISA) may have some utility for the diagnosis of TB in HIV-infected patients; however, the precise subgroup that may benefit from this technology requires clarification. The utility of LAM in sputum samples has, hitherto, not been evaluated.Methods: LAM was measured in sputum and urine samples obtained from 500 consecutively recruited ambulant patients, with suspected TB, from 2 primary care clinics in South Africa. Culture positivity for M. tuberculosis was used as the reference standard for TB diagnosis.Results: Of 440 evaluable patients 120/387 (31%) were HIV-infected. Urine-LAM positivity was associated with HIV positivity (p = 0.007) and test sensitivity, although low, was significantly higher in HIV-infected compared to uninfected patients (21% versus 6%; p<0.001), and also in HIV-infected participants with a CD4 <200 versus <200 cells/mm(3) (37% versus 0%; p = 0.003). Urine-LAM remained highly specific in all 3 subgroups (95%-100%). 25% of smear-negative but culture-positive HIV-infected patients with a CD4 <200 cells/mm(3) were positive for urine-LAM. Sputum-LAM had good sensitivity (86%) but poor specificity (15%) likely due to test cross-reactivity with several mouth-residing organisms including actinomycetes and nocardia species.Conclusions: These preliminary data indicate that in a high burden primary care setting the diagnostic usefulness of urine-LAM is limited, as a rule-in test, to a specific patient subgroup i.e. smear-negative HIV-infected TB patients with a CD4 count <200 cells/mm(3), who would otherwise have required further investigation. However, even in this group sensitivity was modest. Future and adequately powered studies in a primary care setting should now specifically target patients with suspected TB who have advanced HIV infection
Determine TB-LAM lateral flow urine antigen assay for HIV-associated tuberculosis: recommendations on the design and reporting of clinical studies.
No full textDetection of the Mycobacterium tuberculosis cell wall antigen lipoarabinomannan (LAM) in urine permits diagnoses of tuberculosis (TB) to be made in HIV-infected patients with advanced immunodeficiency. This can be achieved at the point-of-care within just 30 minutes using the Determine TB-LAM, which is a commercially available, lateral-flow urine 'strip test' assay. The assay has been shown to have useful diagnostic accuracy in patients enrolling in antiretroviral treatment services or in HIV-infected patients requiring admission to hospital medical wards in sub-Saharan Africa. Such patients have high mortality risk and have most to gain from rapid diagnosis of TB and immediate initiation of treatment. However, few studies using this assay have yet been reported and many questions remain concerning the correct use of the assay, interpretation of results, the role of the assay as an add-on test within existing diagnostic algorithms and the types of further studies needed. In this paper we address a series of questions with the aim of informing the design, conduct and interpretation of future studies. Specifically, we clarify which clinical populations are most likely to derive benefit from use of this assay and how patients enrolled in such studies might best be characterised. We describe the importance of employing a rigorous microbiological diagnostic reference standard in studies of diagnostic accuracy and discuss issues surrounding the specificity of the assay in different geographical areas and potential cross-reactivity with non-tuberculous mycobacteria and other organisms. We highlight the importance of careful procedures for urine collection and storage and the critical issue of how to read and interpret the test strips. Finally, we consider how the assay could be used in combination with other assays and outline the types of studies that are required to build the evidence base concerning its use
Ehrharta erecta Lam., Encycl.
No full textEhrharta erecta Lam., Encycl. 2: 347 (1786). Distribution: Eritrea to S. Africa, Arabian Pen. Specimens: MOSHI Himo, Volkens, G. 1828 (K); Kidia, Hemp, A. 1781 (NHT, UBT); Kilimanjaro Timbers, Grimshaw, J.M. 93254 (K); Kilimanjaro Timbers, Grimshaw, J.M. 94217 (K); Kilimanjaro Timbers, Grimshaw, J.M. 94555 (K); Kilimanjaro Timbers, Grimshaw, J.M. 94621 (K); Londorossi Gate, Peterson, P. 24327 (BC, K, US); Mandara Hut (=Bismark Hut), Grimshaw, J.M. 93808 (K); Mandara Hut (=Bismark Hut), Hitchcock, A.S. 24612 (K); Mandara Hut (=Bismark Hut), Hitchcock, A.S. 24623 (K); Marangu-Mandara track, Hitchcock, A.S. 24647 (K); Mashati, Haarer, A.E. 1719 (K); s. loc., McDonell, M. s.n. (K).Published as part of Prunera-Olivé, Joan, Vorontsova, Maria S., Williams, Emma V., Mollel, Neduvoto P. & Hemp, Andreas, 2021, Checklist of Kilimanjaro grasses shows that both plot and herbarium methods are necessary to record diversity, pp. 201-244 in Phytotaxa 501 (2) on page 223, DOI: 10.11646/phytotaxa.501.2.1, http://zenodo.org/record/542481
Image_1_Proteinase K-pretreated ConA-based ELISA assay: a novel urine LAM detection strategy for TB diagnosis.tif
No full textObjectivesLipoarabinomannan (LAM), an abundant cell wall glycolipid of mycobacteria including Mycobacterium tuberculosis (Mtb), is a promising TB diagnostic marker. The current commercially available urine LAM assays are not sufficiently sensitive, and more novel detection strategies are urgently needed to fill the current diagnostic gap.MethodsA proteinase K-pretreated Concanavalin A (ConA)-based ELISA assay was developed. Diagnostic performance was assessed by several bacterial strains and clinical urine samples.ResultsThe limit of detection (LoD) of the assay against ManLAM was 6 ng/ml. The assay reacted strongly to Mtb H37Rv and M. bovis BCG, intermediately to M. smegmatis mc2155, and weakly to four non-mycobacteria pathogens. This method could distinguish TB patients from healthy controls (HCs) and close contacts (CCs) in 71 urine samples treated with proteinase K, which increases urine LAM antibody reactiveness. In TB+HIV+ and TB+HIV− patients, the sensitivity was 43.8 and 37.5%, respectively, while the specificity was 100.0%. The areas under ROC curves (AUCs) were 0.74 and 0.82, respectively.ConclusionThis study implies that ConA can be paired with antibodies to detect LAM. Proteinase K treatment could effectively enhance the sensitivity by restoring the reactiveness of antibodies to LAM.</p
Paul J. A. Clark, Reinventing China. A Generation and Its Films
No full textRuiz-Lescot Nicolas, Lam Angus W. K. Paul J. A. Clark, Reinventing China. A Generation and Its Films. In: Perspectives chinoises, n°92, 2005. p. 61
A new approach to strong practical stability and stabilization of discrete linear repetitive processes
No full textThe 19th International Symposium on Mathematical Theory of Networks and Systems (MTNS 2010), Budapest, Hungary, 5-9 July 2010
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