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| 14. |
- Saha, S., et al.
(author)
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Observation of rotation about the longest principal axis in Zr 89
- 2019
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In: Physical Review C. - 2469-9985. ; 99:5
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Journal article (peer-reviewed)abstract
- High-spin states in Zr89 were populated in the Se80(C13,4n) reaction, and γ-ray coincidences were measured using the Indian National Gamma Array. The level scheme of Zr89 has been extended up to spin I=49/2 with the observation of a new dipole band. Directional correlation and polarization asymmetries of the γ rays have been measured to determine spin and parity of the levels. Line shapes of several transitions have been analyzed to determine lifetimes of the levels. Possible configurations of the band have been discussed using the cranked Nilsson-Strutinsky model. The calculations suggest a triaxial shape of the nucleus at high spins, and the band may represent rotation of the nucleus about the longest axis.
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| 15. |
- Kumar, V., et al.
(author)
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The Indian Chronic Kidney Disease (ICKD) study: baseline characteristics
- 2022
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In: Clinical Kidney Journal. - : Oxford University Press (OUP). - 2048-8505 .- 2048-8513. ; 15:1, s. 60-69
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Journal article (peer-reviewed)abstract
- Background. Chronic kidney disease (CKD) is an important cause of morbidity and mortality worldwide. There is a lack of information on epidemiology and progression of CKD in low-middle income countries. The Indian Chronic Kidney Disease (ICKD) study aims to identify factors that associate with CKD progression, and development of kidney failure and cardiovascular disease (CVD) in Indian patients with CKD. Methods. ICKD study is prospective, multicentric cohort study enrolling patients with estimated glomerular filtration rate (eGFR) 15-60 mL/min/1.73m(2), or >60 mL/min/1.73m(2) with proteinuria. Clinical details and biological samples are collected at annual visits. We analysed the baseline characteristics including socio-demographic details, risk factors, disease characteristics and laboratory measurements. In addition, we compared characteristics between urban and rural participants. Results. A total of 4056 patients have been enrolled up to 31 March 2020. The mean +/- SD age was 50.3 +/- 11.8 years, 67.2% were males, two-thirds of patients lived in rural areas and the median eGFR was 40 mL/min/1.73m(2). About 87% were hypertensive, 37% had diabetes, 22% had CVD, 6.7% had past history of acute kidney injury and 23% reported prior use of alternative drugs. Diabetic kidney disease, chronic interstitial nephritis (CIN) and CKD-cause unknown (CKDu) were the leading causes. Rural participants had more occupational exposure and tobacco use but lower educational status and income. CIN and unknown categories were leading causes in rural participants. Conclusions. The ICKD study is the only large cohort study of patients with mild-to-moderate CKD in a lower middle income country. Baseline characteristics of study population reveal differences as compared with other cohorts from high-income countries.
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| 17. |
- Chatterjee, S., et al.
(author)
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Protein Paucimannosylation Is an Enriched N-Glycosylation Signature of Human Cancers
- 2019
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In: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 19:21-22
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Journal article (peer-reviewed)abstract
- While aberrant protein glycosylation is a recognized characteristic of human cancers, advances in glycoanalytics continue to discover new associations between glycoproteins and tumorigenesis. This glycomics‐centric study investigates a possible link between protein paucimannosylation, an under‐studied class of human N‐glycosylation [Man1‐3GlcNAc2Fuc0‐1], and cancer. The paucimannosidic glycans (PMGs) of 34 cancer cell lines and 133 tissue samples spanning 11 cancer types and matching non‐cancerous specimens are profiled from 467 published and unpublished PGC‐LC‐MS/MS N‐glycome datasets collected over a decade. PMGs, particularly Man2‐3GlcNAc2Fuc1, are prominent features of 29 cancer cell lines, but the PMG level varies dramatically across and within the cancer types (1.0–50.2%). Analyses of paired (tumor/non‐tumor) and stage‐stratified tissues demonstrate that PMGs are significantly enriched in tumor tissues from several cancer types including liver cancer (p = 0.0033) and colorectal cancer (p = 0.0017) and is elevated as a result of prostate cancer and chronic lymphocytic leukaemia progression (p < 0.05). Surface expression of paucimannosidic epitopes is demonstrated on human glioblastoma cells using immunofluorescence while biosynthetic involvement of N‐acetyl‐β‐hexosaminidase is indicated by quantitative proteomics. This intriguing association between protein paucimannosylation and human cancers warrants further exploration to detail the biosynthesis, cellular location(s), protein carriers, and functions of paucimannosylation in tumorigenesis and metastasis.
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| 18. |
- Prasad, N., et al.
(author)
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Prescription Practices in Patients With Mild to Moderate CKD in India
- 2021
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In: Kidney International Reports. - : Elsevier BV. - 2468-0249. ; 6:9, s. 2455-2462
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Journal article (peer-reviewed)abstract
- Introduction: Patients with chronic kidney disease (CKD) require multiple medications. There is no information on prescription patterns or the use of evidence-based therapies for management of CKD from low-middle-income countries. Using baseline data from the Indian CKD (ICKD) cohort, we describe the drug prescription practices in patients with mild to moderate CKD. Methods: The ICKD study is a prospective, observational cohort study of mild to moderate kidney disease across 11 centers in India. We analyzed all the prescriptions captured at enrollment in the ICKD study. Drugs were categorized into 11 different groups. We provide descriptive data on prescription details and evaluate the appropriateness of medication use. Results: Complete prescription data were available in 3966 out of 4056 (97.8%) subjects enrolled in the ICKD database. Most patients had stage 3 CKD, 24.9% had diabetic kidney disease, 87% had hypertension, and 25.5% had moderate to severe proteinuria. Renin-angiotensin-aldosterone system blockers were prescribed in less than half (47.9%) and in 58.8% of patients with proteinuric CKD. Metformin was prescribed in 25.7% of diabetic subjects with CKD. Only 40.4% of patients were taking statins; 31.1% and 2.8% subjects with anemia were receiving iron and erythropoiesis-stimulating agents, respectively. Conclusion: This study highlights the missed opportunities for improving outcomes through appropriate prescriptions of drugs in patients with CKD. There is need for dissemination of evidence-based guidelines and institution of sustainable implementation practices for improving the overall health of patients with CKD. © 2021 International Society of Nephrology
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| 20. |
- Singh, Purnima, et al.
(author)
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High-spin spectroscopy of I-122
- 2012
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In: Physical Review C (Nuclear Physics). - 0556-2813. ; 85:5
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Journal article (peer-reviewed)abstract
- High-spin states in I-122 have been investigated using the Cd-116(B-11,5n)I-122 reaction at a beam energy of 65 MeV and gamma-ray coincidence events were recorded with the INGA spectrometer. The level scheme of I-122 has been extended up to spin I = 30. Experimental features, such as band-crossing frequencies, aligned angular momenta, signature splitting, and B(M1)/B(E2) ratios have been used for configuration assignments to low-energy band structures. Maximally aligned states involving all eight particles outside the Sn-114 core and states with one particle antialigned have been identified. Cranked Nilsson-Strutinsky calculations have been used to interpret high-spin structures.
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| 24. |
- Barbateskovic, Marija, et al.
(author)
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A new tool to assess Clinical Diversity In Meta-analyses (CDIM) of interventions
- 2021
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In: Journal of Clinical Epidemiology. - : Elsevier BV. - 0895-4356 .- 1878-5921. ; 135, s. 29-41
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Journal article (peer-reviewed)abstract
- Objective: To develop and validate Clinical Diversity In Meta-analyses (CDIM), a new tool for assessing clinical diversity between trials in meta-analyses of interventions. Study design and setting: The development of CDIM was based on consensus work informed by empirical literature and expertise. We drafted the CDIM tool, refined it, and validated CDIM for interrater scale reliability and agreement in three groups. Results: CDIM measures clinical diversity on a scale that includes four domains with 11 items overall: setting (time of conduct/country development status/units type); population (age, sex, patient inclusion criteria/baseline disease severity, comorbidities); interventions (intervention intensity/strength/duration of intervention, timing, control intervention, cointerventions); and outcome (definition of outcome, timing of outcome assessment). The CDIM is completed in two steps: first two authors independently assess clinical diversity in the four domains. Second, after agreeing upon scores of individual items a consensus score is achieved. Interrater scale reliability and agreement ranged from moderate to almost perfect depending on the type of raters. Conclusion: CDIM is the first tool developed for assessing clinical diversity in meta-analyses of interventions. We found CDIM to be a reliable tool for assessing clinical diversity among trials in meta-analysis.
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| 25. |
- Briend, Emmanuel, et al.
(author)
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IL-18 associated with lung lymphoid aggregates drives IFNγ production in severe COPD
- 2017
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In: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 18:1
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Journal article (peer-reviewed)abstract
- Background: Increased interferon gamma (IFNγ) release occurs in Chronic Obstructive Pulmonary Disease (COPD) lungs. IFNγ supports optimal viral clearance, but if dysregulated could increase lung tissue destruction. Methods: The present study investigates which mediators most closely correlate with IFNγ in sputum in stable and exacerbating disease, and seeks to shed light on the spatial requirements for innate production of IFNγ, as reported in mouse lymph nodes, to observe whether such microenvironmental cellular organisation is relevant to IFNγ production in COPD lung. Results: We show tertiary follicle formation in severe disease alters the dominant mechanistic drivers of IFNγ production, because cells producing interleukin-18, a key regulator of IFNγ, are highly associated with such structures. Interleukin-1 family cytokines correlated with IFNγ in COPD sputum. We observed that the primary source of IL-18 in COPD lungs was myeloid cells within lymphoid aggregates and IL-18 was increased in severe disease. IL-18 released from infected epithelium or from activated myeloid cells, was more dominant in driving IFNγ when IL-18-producing and responder cells were in close proximity. Conclusions: Unlike tight regulation to control infection spread in lymphoid organs, this local interface between IL-18-expressing and responder cell is increasingly supported in lung as disease progresses, increasing its potential to increase tissue damage via IFNγ.
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| 28. |
- Görür, Yunus Can, et al.
(author)
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Rapidly Prepared Nanocellulose Hybrids as Gas Barrier, Flame Retardant, and Energy Storage Materials
- 2022
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In: ACS Applied Nano Materials. - : American Chemical Society (ACS). - 2574-0970. ; 5:7, s. 9188-9200
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Journal article (peer-reviewed)abstract
- Cellulose nanofibril (CNF) hybrid materials show great promise as sustainable alternatives to oil-based plastics owing to their abundance and renewability. Nonetheless, despite the enormous success achieved in preparing CNF hybrids at the laboratory scale, feasible implementation of these materials remains a major challenge due to the time-consuming and energy-intensive extraction and processing of CNFs. Here, we describe a scalable materials processing platform for rapid preparation (<10 min) of homogeneously distributed functional CNF-gibbsite and CNF-graphite hybrids through a pH-responsive self-assembly mechanism, followed by their application in gas barrier, flame retardancy, and energy storage materials. Incorporation of 5 wt % gibbsite results in strong, transparent, and oxygen barrier CNF-gibbsite hybrid films in 9 min. Increasing the gibbsite content to 20 wt % affords them self-extinguishing properties, while further lowering their dewatering time to 5 min. The strategy described herein also allows for the preparation of freestanding CNF-graphite hybrids (90 wt % graphite) that match the energy storage performance (330 mA h/g at low cycling rates) and processing speed (3 min dewatering) of commercial graphite anodes. Furthermore, these ecofriendly electrodes can be fully recycled, reformed, and reused while maintaining their initial performance. Overall, this versatile concept combines a green outlook with high processing speed and material performance, paving the way toward scalable processing of advanced ecofriendly hybrid materials.
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| 30. |
- Kvedaraite, E, et al.
(author)
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Notch-dependent cooperativity between myeloid lineages promotes Langerhans cell histiocytosis pathology
- 2022
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In: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 7:78, s. eadd3330-
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Journal article (peer-reviewed)abstract
- Langerhans cell histiocytosis (LCH) is a potentially fatal neoplasm characterized by the aberrant differentiation of mononuclear phagocytes, driven by mitogen-activated protein kinase (MAPK) pathway activation. LCH cells may trigger destructive pathology yet remain in a precarious state finely balanced between apoptosis and survival, supported by a unique inflammatory milieu. The interactions that maintain this state are not well known and may offer targets for intervention. Here, we used single-cell RNA-seq and protein analysis to dissect LCH lesions, assessing LCH cell heterogeneity and comparing LCH cells with normal mononuclear phagocytes within lesions. We found LCH discriminatory signatures pointing to senescence and escape from tumor immune surveillance. We also uncovered two major lineages of LCH with DC2- and DC3/monocyte-like phenotypes and validated them in multiple pathological tissue sites by high-content imaging. Receptor-ligand analyses and lineage tracing in vitro revealed Notch-dependent cooperativity between DC2 and DC3/monocyte lineages during expression of the pathognomonic LCH program. Our results present a convergent dual origin model of LCH with MAPK pathway activation occurring before fate commitment to DC2 and DC3/monocyte lineages and Notch-dependent cooperativity between lineages driving the development of LCH cells.
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| 31. |
- Kyprianidis, Konstantinos, et al.
(author)
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Uncertainty in gas turbine thermo-fluid modelling and its impact on performance calculations and emissions predictions at aircraft system level
- 2012
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In: Proceedings of the Institution of Mechanical Engineers, Part G: Journal of Aerospace Engineering. - : SAGE Publications. - 0954-4100 .- 2041-3025. ; 226:2, s. 163-181
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Journal article (peer-reviewed)abstract
- In this article, various aspects of thermo-fluid modelling for gas turbines are described and the impact on performance calculations and emissions predictions at aircraft system level is assessed. Accurate and reliable fluid modelling is essential for any gas turbine performance simulation software as it provides a robust foundation for building advanced multi-disciplinary modelling capabilities. Caloric properties for generic and semi-generic gas turbine performance simulation codes can be calculated at various levels of fidelity; selection of the fidelity level is dependent upon the objectives of the simulation and execution time constraints. However, rigorous fluid modelling may not necessarily improve performance simulation accuracy unless all modelling assumptions and sources of uncertainty are aligned to the same level.A comprehensive analysis of thermo-fluid modelling for gas turbines is presented, and the fluid models developed are discussed in detail. Common technical models, used for calculating caloric properties, are compared while typical assumptions made in fluid modelling, and the uncertainties induced, are examined. Several analyses, which demonstrate the effects of composition, temperature, and pressure on caloric properties of working media for gas turbines, are presented. The working media examined include dry air and combustion products for various fuels and H/C ratios. The uncertainty induced in calculations by (a) using common technical models for evaluating fluid caloric properties and (b) ignoring dissociation effects is examined at three different levels: (i) component level, (ii) engine level, and (iii) aircraft system level. An attempt is made to shed light on the trade-off between improving the accuracy of a fluid model and the accuracy of a multi-disciplinary simulation at aircraft system level, against computational time penalties. The validity of the ideal gas assumption for future turbofan engines and novel propulsion cycles is discussed. The results obtained demonstrate that accurate modelling of the working fluid is essential, especially for assessing novel and/or aggressive cycles at aircraft system level. Where radical design space exploration is concerned, improving the accuracy of the fluid model will need to be carefully balanced with the computational time penalties involved.
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| 32. |
- La Merrill, M. A., et al.
(author)
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Perinatal DDT Exposure Induces Hypertension and Cardiac Hypertrophy in Adult Mice
- 2016
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In: Environmental Health Perspectives. - 0091-6765. ; 124:11, s. 1722-1727
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Journal article (peer-reviewed)abstract
- BACKGROUND: Dichlorodiphenyltrichloroethane (DDT) was used extensively to control malaria, typhus, body lice, and bubonic plague worldwide, until countries began restricting its use in the 1970s. However, the use of DDT to control vector-borne diseases continues in developing countries. Prenatal DDT exposure is associated with elevated blood pressure in humans. OBJECTIVE: We hypothesized that perinatal DDT exposure causes hypertension in adult mice. METHODS: DDT was administered to C57BL/6J dams from gestational day 11.5 to postnatal day 5. Blood pressure (BP) and myocardial wall thickness were measured in male and female adult offspring. Adult mice were treated with an angiotensin converting enzyme (ACE) inhibitor, captopril, to evaluate sensitivity to amelioration of DDT-associated hypertension by ACE inhibition. We further assessed the influence of DDT exposure on the expression of mRNAs that regulate BP through renal ion transport. RESULTS: Adult mice perinatally exposed to DDT exhibited chronically increased systolic BP, increased myocardial wall thickness, and elevated expression of mRNAs of several renal ion transporters. Captopril completely reversed hypertension in mice perinatally exposed to DDT. CONCLUSIONS: These data demonstrate that perinatal exposure to DDT causes hypertension and cardiac hypertrophy in adult offspring. A key mechanism underpinning this hypertension is an overactivated renin angiotensin system because ACE inhibition reverses the hypertension induced by perinatal DDT exposure.
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| 33. |
- Lagathu, C., et al.
(author)
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Secreted frizzled-related protein 1 regulates adipose tissue expansion and is dysregulated in severe obesity.
- 2010
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In: International Journal of Obesity. - London, United Kingdom : Nature Publishing Group. - 0307-0565 .- 1476-5497. ; 34:12, s. 1695-1705
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Journal article (peer-reviewed)abstract
- AIM: The Wnt/β-catenin signaling network offers potential targets to diagnose and uncouple obesity from its metabolic complications. In this study, we investigate the role of the Wnt antagonist, secreted frizzled-related protein 1 (SFRP1), in promoting adipogenesis in vitro and adipose tissue expansion in vivo.METHODS: We use a combination of human and murine, in vivo and in vitro models of adipogenesis, adipose tissue expansion and obesity-related metabolic syndrome to profile the involvement of SFRP1.RESULTS: SFRP1 is expressed in both murine and human mature adipocytes. The expression of SFRP1 is induced during in vitro adipogenesis, and SFRP1 is preferentially expressed in mature adipocytes in human adipose tissue. Constitutive ectopic expression of SFRP1 is proadipogenic and inhibits the Wnt/β-catenin signaling pathway. In vivo endogenous levels of adipose SFRP1 are regulated in line with proadipogenic states. However, in longitudinal studies of high-fat-diet-fed mice, we observed a dynamic temporal but biphasic regulation of endogenous SFRP1. In agreement with this profile, we observed that SFRP1 expression in human tissues peaks in patients with mild obesity and gradually falls in morbidly obese subjects.CONCLUSIONS: Our results suggest that SFRP1 is an endogenous modulator of Wnt/β-catenin signaling and participates in the paracrine regulation of human adipogenesis. The reduced adipose expression of SFRP1 in morbid obesity and its knock-on effect to prevent further adipose tissue expansion may contribute to the development of metabolic complications in these individuals.
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| 34. |
- Liu, Bing, et al.
(author)
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A Computational and Experimental Study of the Regulatory Mechanisms of the Complement System
- 2011
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In: PLoS Computational Biology. - : Public Library of Science (PLoS). - 1553-7358. ; 70:1
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Journal article (peer-reviewed)abstract
- The complement system is key to innate immunity and its activation is necessary for the clearance of bacteria and apoptotic cells. However, insufficient or excessive complement activation will lead to immune-related diseases. It is so far unknown how the complement activity is up- or down-regulated and what the associated pathophysiological mechanisms are. To quantitatively understand the modulatory mechanisms of the complement system, we built a computational model involving the enhancement and suppression mechanisms that regulate complement activity. Our model consists of a large system of Ordinary Differential Equations (ODEs) accompanied by a dynamic Bayesian network as a probabilistic approximation of the ODE dynamics. Applying Bayesian inference techniques, this approximation was used to perform parameter estimation and sensitivity analysis. Our combined computational and experimental study showed that the antimicrobial response is sensitive to changes in pH and calcium levels, which determines the strength of the crosstalk between CRP and L-ficolin. Our study also revealed differential regulatory effects of C4BP. While C4BP delays but does not decrease the classical complement activation, it attenuates but does not significantly delay the lectin pathway activation. We also found that the major inhibitory role of C4BP is to facilitate the decay of C3 convertase. In summary, the present work elucidates the regulatory mechanisms of the complement system and demonstrates how the bio-pathway machinery maintains the balance between activation and inhibition. The insights we have gained could contribute to the development of therapies targeting the complement system.
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| 35. |
- MacKinnon, Alison C, et al.
(author)
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Regulation of alternative macrophage activation by galectin-3
- 2008
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In: Journal of Immunology. - 1550-6606. ; 180:4, s. 2650-2658
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Journal article (peer-reviewed)abstract
- Alternative macrophage activation is implicated in diverse disease pathologies such as asthma, organ fibrosis, and granulomatous diseases, but the mechanisms underlying macrophage programming are not fully understood. Galectin-3 is a carbohydrate-binding lectin present on macrophages. We show that disruption of the galectin-3 gene in 129sv mice specifically restrains IL-4/IL-13-induced alternative macrophage activation in bone marrow-derived macrophages in vitro and in resident lung and recruited peritoneal macrophages in vivo without affecting IFN-gamma/LPS-induced classical activation or IL-10-induced deactivation. IL-4-mediated alternative macrophage activation is inhibited by siRNA-targeted deletion of galectin-3 or its membrane receptor CD98 and by inhibition of PI3K. Increased galectin-3 expression and secretion is a feature of alternative macrophage activation. IL-4 stimulates galectin-3 expression and release in parallel with other phenotypic markers of alternative macrophage activation. By contrast, classical macrophage activation with LPS inhibits galectin-3 expression and release. Galectin-3 binds to CD98, and exogenous galectin-3 or cross-linking CD98 with the mAb 4F2 stimulates PI3K activation and alternative activation. IL-4-induced alternative activation is blocked by bis-(3-deoxy-3-(3-methoxybenzamido)-beta-D-galactopyranosyl) sulfane, a specific inhibitor of extracellular galectin-3 carbohydrate binding. These results demonstrate that a galectin-3 feedback loop drives alternative macrophage activation. Pharmacological modulation of galectin-3 function represents a novel therapeutic strategy in pathologies associated with alternatively activated macrophages.
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| 41. |
- Sethi, Jatin, et al.
(author)
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Smart polymer coatings for protection from corrosion
- 2020
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In: Smart Polymer Nanocomposites. - : Elsevier BV. ; , s. 399-413
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Book chapter (other academic/artistic)abstract
- In this chapter, various novel and well-noted approaches for corrosion preventive coatings have been discussed. Very well-documented factors that affect the corrosion mechanism are environmental factors, metal, and surface conditions and are elaborated in detail. Various modern, highly approachable, and currently used coating approaches are expanded and explained. This chapter provides a full view of the modern techniques used for corrosion prevention and cure.
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| 42. |
- Sethi, Jatin, et al.
(author)
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Ultra-thin parylene-aluminium hybrid coatings on nanocellulose films to resist water sensitivity
- 2024
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In: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617 .- 1879-1344. ; 323, s. 121365-
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Journal article (peer-reviewed)abstract
- Non-sustainable single-use plastics used for food packaging needs to be phased out. Films made from cellulose nanofibrils (CNFs) are suitable candidates for biodegradable and recyclable packaging materials as they exhibit good mechanical properties, excellent oxygen barrier properties and high transparency. Yet, their poor water vapour barrier properties have been a major hindrance in their commercialisation. Here, we describe the preparation of 25 μm thick CNF films with significantly improved water vapour barrier properties after deposition of ultrathin polymeric and metallic coatings, parylene C and aluminium, respectively. When first adding a 40 nm aluminium layer followed by an 80 nm parylene layer, i.e. with a combined thickness of less than one percent of the CNF film, a water vapour transmission rate of 2.8 g m−2 d−1 was achieved at 38 °C and 90 % RH, surpassing a 25 μm polypropylene film (4–12 g m−2 d−1). This is an improvement of more than 700 times compared to uncoated CNF films, under some of the harshest possible conditions a packaging material will need to endure in commercial use. The layers showed a good and even coverage, as assessed by atomic force microscopy, and the parylene-coated surfaces were hydrophobic with a contact angle of 110°, providing good water repellency.
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| 45. |
- Smith, JAB, et al.
(author)
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Three weeks of interrupting sitting lowers fasting glucose and glycemic variability, but not glucose tolerance, in free-living women and men with obesity
- 2021
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In: American journal of physiology. Endocrinology and metabolism. - : American Physiological Society. - 1522-1555 .- 0193-1849. ; 321:2, s. E203-E216
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Journal article (peer-reviewed)abstract
- Under free-living conditions, breaking sitting modestly increased activity behavior. Breaking sitting was insufficient to modulate glucose tolerance or the skeletal muscle lipidome. Activity breaks reduced fasting blood glucose levels and daily glucose variation compared with baseline, with a tendency to also decrease fasting LDLc. This intervention may represent the minimal dose for breaking sedentary behavior, with larger volumes of activity possibly required to promote greater health benefits.
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