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| 19. |
- Kvedaraite, E, et al.
(författare)
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Notch-dependent cooperativity between myeloid lineages promotes Langerhans cell histiocytosis pathology
- 2022
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Ingår i: Science immunology. - : American Association for the Advancement of Science (AAAS). - 2470-9468. ; 7:78, s. eadd3330-
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Tidskriftsartikel (refereegranskat)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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| 20. |
- Hirani, Nikhil, et al.
(författare)
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Target inhibition of galectin-3 by inhaled TD139 in patients with idiopathic pulmonary fibrosis
- 2021
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Ingår i: European Respiratory Journal. - : European Respiratory Society (ERS). - 0903-1936 .- 1399-3003. ; 57:5
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Tidskriftsartikel (refereegranskat)abstract
- Galectin (Gal)-3 is a profibrotic β-galactoside-binding lectin that plays a key role in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and IPF exacerbations. TD139 is a novel and potent small-molecule inhibitor of Gal-3. A randomised, double-blind, multicentre, placebo-controlled, phase 1/2a study was conducted to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of inhaled TD139 in 36 healthy subjects and 24 patients with IPF. Six dose cohorts of six healthy subjects were evaluated (4:2 TD139:placebo ratio) with single doses of TD139 (0.15–50 mg) and three dose cohorts of eight patients with IPF (5:3 TD139: placebo ratio) with once-daily doses of TD139 (0.3–10 mg) for 14 days. Inhaled TD139 was well tolerated with no significant treatment-related side-effects. TD139 was rapidly absorbed, with mean time taken to reach maximum plasma concentration (Cmax) values ranging from 0.6 to 3 h and a plasma half-life (T1/2) of 8 h. The concentration of TD139 in the lung was >567-fold higher than in the blood, with systemic exposure predicting exposure in the target compartment. Gal-3 expression on alveolar macrophages was reduced in the 3 and 10 mg dose groups compared with placebo, with a concentration-dependent inhibition demonstrated. Inhibition of Gal-3 expression in the lung was associated with reductions in plasma biomarkers centrally relevant to IPF pathobiology (platelet-derived growth factor-BB, plasminogen activator inhibitor-1, Gal-3, CCL18 and YKL-40). TD139 is safe and well tolerated in healthy subjects and IPF patients. It was shown to suppress Gal-3 expression on bronchoalveolar lavage macrophages and, in a concerted fashion, decrease plasma biomarkers associated with IPF progression.
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| 21. |
- Kumar, V., et al.
(författare)
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The Indian Chronic Kidney Disease (ICKD) study: baseline characteristics
- 2022
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Ingår i: Clinical Kidney Journal. - : Oxford University Press (OUP). - 2048-8505 .- 2048-8513. ; 15:1, s. 60-69
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Tidskriftsartikel (refereegranskat)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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| 22. |
- Prasad, N., et al.
(författare)
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Prescription Practices in Patients With Mild to Moderate CKD in India
- 2021
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Ingår i: Kidney International Reports. - : Elsevier BV. - 2468-0249. ; 6:9, s. 2455-2462
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Tidskriftsartikel (refereegranskat)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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| 27. |
- Briend, Emmanuel, et al.
(författare)
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IL-18 associated with lung lymphoid aggregates drives IFNγ production in severe COPD
- 2017
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Ingår i: Respiratory Research. - : Springer Science and Business Media LLC. - 1465-9921 .- 1465-993X. ; 18:1
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Tidskriftsartikel (refereegranskat)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. |
- Gustavsson, Emil K., et al.
(författare)
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The annotation of GBA1 has been concealed by its protein-coding pseudogene GBAP1
- 2024
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Ingår i: Science Advances. - 2375-2548. ; 10:26, s. 1-20
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Tidskriftsartikel (refereegranskat)abstract
- Mutations in GBA1 cause Gaucher disease and are the most important genetic risk factor for Parkinson’s disease. However, analysis of transcription at this locus is complicated by its highly homologous pseudogene, GBAP1. We show that >50% of short RNA-sequencing reads mapping to GBA1 also map to GBAP1. Thus, we used long-read RNA sequencing in the human brain, which allowed us to accurately quantify expression from both GBA1 and GBAP1. We discovered significant differences in expression compared to short-read data and identify currently unannotated transcripts of both GBA1 and GBAP1. These included protein-coding transcripts from both genes that were translated in human brain, but without the known lysosomal function—yet accounting for almost a third of transcription. Analyzing brain-specific cell types using long-read and single-nucleus RNA sequencing revealed region-specific variations in transcript expression. Overall, these findings suggest nonlysosomal roles for GBA1 and GBAP1 with implications for our understanding of the role of GBA1 in health and disease.
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| 30. |
- MacKinnon, Alison C., et al.
(författare)
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Regulation of Transforming Growth Factor-beta 1-driven Lung Fibrosis by Galectin-3
- 2012
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Ingår i: American Journal of Respiratory and Critical Care Medicine. - 1535-4970. ; 185:5, s. 537-546
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Tidskriftsartikel (refereegranskat)abstract
- Rationale: Idiopathic pulmonary fibrosis (IPF) is a chronic dysregulated response to alveolar epithelial injury with differentiation of epithelial cells and fibroblasts into matrix-secreting myofibroblasts resulting in lung scaring. The prognosis is poor and there are no effective therapies or reliable biomarkers. Galectin-3 is a beta-galactoside binding lectin that is highly expressed in fibrotic tissue of diverse etiologies. Objectives: To examine the role of galectin-3 in pulmonary fibrosis. Methods: We used genetic deletion and pharmacologic inhibition in well-characterized murine models of lung fibrosis. Further mechanistic studies were performed in vitro and on samples from patients with IPF. Measurements and Main Results: Transforming growth factor (TGF)-beta and bleomycin-induced lung fibrosis was dramatically reduced in mice deficient in galectin-3, manifest by reduced TGF-beta 1 induced EMT and myofibroblast activation and collagen production. Galectin-3 reduced phosphorylation and nuclear translocation of beta-catenin but had no effect on Smad2/3 phosphorylation. A novel inhibitor of galectin -3, TD139, blocked TGF-beta-induced beta-catenin activation in vitro and in vivo and attenuated the late-stage progression of lung fibrosis after bleomycin. There was increased expression of galectin-3 in the bronchoalveolar lavage fluid and serum from patients with stable IPF compared with nonspecific interstitial pneumonitis and controls, which rose sharply during an acute exacerbation suggesting that. galectin-3 may be a marker of active fibrosis in IPF and that strategies that block galectin-3 may be effective in treating acute fibrotic exacerbations of IPF. Conclusions: This study identifies galectin-3 as an important regulator of lung fibrosis and provides a proof of principle for galectin-3 inhibition as a potential novel therapeutic strategy for IPF.
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| 31. |
- Rabiee, Navid, et al.
(författare)
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Green Biomaterials : fundamental principles
- 2023
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Ingår i: Green Biomaterials. - : Taylor & Francis. - 2993-4168. ; 1:1, s. 1-4
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 32. |
- Saha, S., et al.
(författare)
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Observation of rotation about the longest principal axis in Zr 89
- 2019
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Ingår i: Physical Review C. - 2469-9985. ; 99:5
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Tidskriftsartikel (refereegranskat)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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| 34. |
- Singh, Purnima, et al.
(författare)
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High-spin spectroscopy of I-122
- 2012
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Ingår i: Physical Review C (Nuclear Physics). - 0556-2813. ; 85:5
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Tidskriftsartikel (refereegranskat)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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| 36. |
- Chatterjee, S., et al.
(författare)
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Protein Paucimannosylation Is an Enriched N-Glycosylation Signature of Human Cancers
- 2019
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Ingår i: Proteomics. - : Wiley. - 1615-9853 .- 1615-9861. ; 19:21-22
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Tidskriftsartikel (refereegranskat)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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| 37. |
- Delaine, Tamara, et al.
(författare)
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Galectin-3-Binding Glycomimetics that Strongly Reduce Bleomycin-Induced Lung Fibrosis and Modulate Intracellular Glycan Recognition
- 2016
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Ingår i: ChemBioChem. - : Wiley. - 1439-4227. ; 17:18, s. 1759-1770
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Tidskriftsartikel (refereegranskat)abstract
- Discovery of glycan-competitive galectin-3-binding compounds that attenuate lung fibrosis in a murine model and that block intracellular galectin-3 accumulation at damaged vesicles, hence revealing galectin-3-glycan interactions involved in fibrosis progression and in intracellular galectin-3 activities, is reported. 3,3'-Bis-(4-aryltriazol-1-yl)thiodigalactosides were synthesized and evaluated as antagonists of galectin-1, -2, -3, and -4 N-terminal, -4 C-terminal, -7 and -8 N-terminal, -9 N-terminal, and -9 C-terminal domains. Compounds displaying low-nanomolar affinities for galectins-1 and -3 were identified in a competitive fluorescence anisotropy assay. X-ray structural analysis of selected compounds in complex with galectin-3, together with galectin-3 mutant binding experiments, revealed that both the aryltriazolyl moieties and fluoro substituents on the compounds are involved in key interactions responsible for exceptional affinities towards galectin-3. The most potent galectin-3 antagonist was demonstrated to act in an assay monitoring galectin-3 accumulation upon amitriptyline-induced vesicle damage, visualizing a biochemically/medically relevant intracellular lectin-carbohydrate binding event and that it can be blocked by a small molecule. The same antagonist administered intratracheally attenuated bleomycin-induced pulmonary fibrosis in a mouse model with a dose/response profile comparing favorably with that of oral administration of the marketed antifibrotic compound pirfenidone.
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| 38. |
- Fuhlbrigge, Anne L., et al.
(författare)
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A novel endpoint for exacerbations in asthma to accelerate clinical development : A post-hoc analysis of randomised controlled trials
- 2017
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Ingår i: The Lancet Respiratory Medicine. - 2213-2600. ; 5:7, s. 577-590
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Tidskriftsartikel (refereegranskat)abstract
- Background: Occurrence of severe asthma exacerbations are the cornerstone of the evaluation of asthma management, but severe asthma exacerbations are rare events. Therefore, trials that assess drug efficacy on exacerbations are done late in clinical development programmes. We aimed to establish an endpoint capturing clinically relevant deteriorations (diary events) that, when combined with severe exacerbations, create a composite outcome (CompEx). CompEx needs to strongly mirror results seen with the severe exacerbation-validated outcome, to allow the design of clinical trials of shorter duration and that include fewer patients than trials assessing severe exacerbations. Methods: Data from 12 asthma trials of 6 months or 12 months duration and, with standardised collection of exacerbations and diary card variables, were used to construct and test CompEx. The study populations had a mean age of 35-53 years, 59-69% were female, and had a mean FEV1 percentage of predicted normal of 63-84%. With data from five trials, we established a series of diary events based on peak expiratory flow (P), reliever use (R), symptoms (S), awakenings (A), and threshold values for change from baseline and slopes to assess trends. For the development phase, we evaluated different variable combinations and deterioration criteria to select the most robust algorithm to define a diary event for the composite outcome. We defined a composite outcome, CompEx, as first occurrence of a diary event or a severe exacerbation. We assessed the performance of CompEx in seven trials by comparing the event frequency, treatment effect (hazard ratio; HR), and the sample size needed for future trials for the CompEx versus episodes of severe exacerbations. Findings: CompEx (based on PRS) was the algorithm that best fulfilled our two-set criteria. When censored at 3 months, CompEx resulted in 2·8 times more events than severe exacerbations, and while preserving the treatment effect observed on severe exacerbations (CompEx over severe exacerbation average HR 1·01). The increased number of events, together with the sustained treatment effect, resulted in a large net gain in power, with a 67% mean reduction in the number of patients required in a drug trial for severe exacerbations. In six of seven comparisons tested, CompEx reduced the sample size needed by at least 50%. Validation of independent test populations confirmed the ability of CompEx to increase event frequencies, preserve treatment effect, and reduce the number of patients needed. Interpretation: CompEx is a composite outcome for evaluation of new asthma therapies. CompEx allows design of shorter trials that require fewer patients than studies of severe exacerbations, while preserving the ability to show a treatment effect compared with severe exacerbations. Funding: AstraZeneca.
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| 41. |
- Görür, Yunus Can, et al.
(författare)
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Rapidly Prepared Nanocellulose Hybrids as Gas Barrier, Flame Retardant, and Energy Storage Materials
- 2022
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Ingår i: ACS Applied Nano Materials. - : American Chemical Society (ACS). - 2574-0970. ; 5:7, s. 9188-9200
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Tidskriftsartikel (refereegranskat)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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| 42. |
- Haq, M. U., et al.
(författare)
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Capsule Network with Its Limitation, Modification, and Applications—A Survey
- 2023
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Ingår i: Machine Learning and Knowledge Extraction. - : Multidisciplinary Digital Publishing Institute (MDPI). - 2504-4990. ; 5:3, s. 891-921
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Tidskriftsartikel (refereegranskat)abstract
- Numerous advancements in various fields, including pattern recognition and image classification, have been made thanks to modern computer vision and machine learning methods. The capsule network is one of the advanced machine learning algorithms that encodes features based on their hierarchical relationships. Basically, a capsule network is a type of neural network that performs inverse graphics to represent the object in different parts and view the existing relationship between these parts, unlike CNNs, which lose most of the evidence related to spatial location and requires lots of training data. So, we present a comparative review of various capsule network architectures used in various applications. The paper’s main contribution is that it summarizes and explains the significant current published capsule network architectures with their advantages, limitations, modifications, and applications.
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| 43. |
- Kyprianidis, Konstantinos, et al.
(författare)
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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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Ingår i: 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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Tidskriftsartikel (refereegranskat)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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| 44. |
- La Merrill, M. A., et al.
(författare)
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Perinatal DDT Exposure Induces Hypertension and Cardiac Hypertrophy in Adult Mice
- 2016
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Ingår i: Environmental Health Perspectives. - 0091-6765. ; 124:11, s. 1722-1727
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Tidskriftsartikel (refereegranskat)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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| 45. |
- Lagathu, C., et al.
(författare)
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Secreted frizzled-related protein 1 regulates adipose tissue expansion and is dysregulated in severe obesity.
- 2010
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Ingår i: International Journal of Obesity. - London, United Kingdom : Nature Publishing Group. - 0307-0565 .- 1476-5497. ; 34:12, s. 1695-1705
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Tidskriftsartikel (refereegranskat)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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| 46. |
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| 47. |
- Najafi Saatlou, Esmail, et al.
(författare)
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On the trade-off between minimum fuel burn and maximum time between overhaul for an intercooled aeroengine
- 2014
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Ingår i: Proceedings of the Institution of Mechanical Engineers, Part G: Journal of Aerospace Engineering. - IMechE : SAGE Publications. - 0954-4100 .- 2041-3025. ; 228:13, s. 2424-2438
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Tidskriftsartikel (refereegranskat)abstract
- A large variety of promising power and propulsion system concepts are being proposed to reduce carbon dioxide and other emissions. However, the best candidate to pursue is difficult to select and it is imperative that major investments are correctly targeted to deliver environmentally friendly, economical and reliable solutions. To conceive and assess gas turbine engines with minimum environmental impact and lowest cost of ownership in a variety of emission legislation scenarios and emissions taxation policies, a tool based on a techno-economic and environmental risk assessment methodology is required. A tool based on this approach has been developed by the authors. The core of the tool is a detailed and rigorous thermodynamic representation of power plants, around which other modules can be coupled (that model different disciplines such as aircraft performance, economics, emissions, noise, weight and cost) resulting in a multidisciplinary framework. This approach can be used for efficient and cost-effective design space exploration in the civil aviation, power generation, marine, and oil and gas fields. In the present work, a conceptual intercooled core aeroengine design was assessed with component technologies consistent with 2020 entry into service via a multidisciplinary optimisation approach. Such an approach is necessary to assess the trade-off between asset life, operating costs and technical specification. This paper examines the influence of fuel consumption, engine weight and direct operating costs with respect to extending the engine life. The principal modes of failure such as creep, fatigue and oxidation, are considered in the engine life estimation. Multidisciplinary optimisation, comprising the main engine design parameters, was carried out with maximum time between overhaul as the objective function. The trade-off between minimum block fuel burn and maximum engine life was examined; the results were compared against the initial engine design and an assessment was made to identify the design changes required for obtaining an improved engine design in terms of direct operating costs. The results obtained from the study demonstrate that an engine optimised for maximum time between overhaul requires a lower overall pressure ratio and specific thrust but this comes at the cost of lower thermal efficiency and higher engine production costs.
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| 48. |
- Sajic, Tatjana, et al.
(författare)
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Similarities and Differences of Blood N-Glycoproteins in Five Solid Carcinomas at Localized Clinical Stage Analyzed by SWATH-MS
- 2018
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Ingår i: Cell Reports. - : Elsevier BV. - 2211-1247. ; 23:9, s. 5-2831
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Tidskriftsartikel (refereegranskat)abstract
- Cancer is mostly incurable when diagnosed at a metastatic stage, making its early detection via blood proteins of immense clinical interest. Proteomic changes in tumor tissue may lead to changes detectable in the protein composition of circulating blood plasma. Using a proteomic workflow combining N-glycosite enrichment and SWATH mass spectrometry, we generate a data resource of 284 blood samples derived from patients with different types of localized-stage carcinomas and from matched controls. We observe whether the changes in the patient's plasma are specific to a particular carcinoma or represent a generic signature of proteins modified uniformly in a common, systemic response to many cancers. A quantitative comparison of the resulting N-glycosite profiles discovers that proteins related to blood platelets are common to several cancers (e.g., THBS1), whereas others are highly cancer-type specific. Available proteomics data, including a SWATH library to study N-glycoproteins, will facilitate follow-up biomarker research into early cancer detection. Sajic et al. perform a multi-tumor plasma proteomic study in which they enrich and analyze tissue-secreted plasma glycoproteins to examine blood protein changes in early-stage localized cancers. They demonstrate that many proteins secreted upon platelet activation are changed in several tissue carcinomas, whereas others have changes specific to a single carcinoma type.
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| 49. |
- Sethi, Jatin, et al.
(författare)
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Ultra-thin parylene-aluminium hybrid coatings on nanocellulose films to resist water sensitivity
- 2024
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Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617 .- 1879-1344. ; 323, s. 121365-
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Tidskriftsartikel (refereegranskat)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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| 50. |
- Sethi, Jatin, et al.
(författare)
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Water-resistant hybrid cellulose nanofibril films prepared by charge reversal on gibbsite nanoclays
- 2022
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Ingår i: Carbohydrate Polymers. - : Elsevier BV. - 0144-8617 .- 1879-1344. ; 295
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Tidskriftsartikel (refereegranskat)abstract
- A novel method is reported for the preparation of a hybrid gibbsite-cellulose nanofibril (CNF) nanocomposite film with improved wet and dry mechanical properties and barrier properties. A gibbsite and cationic CNF dispersion was dewatered at pH 7 to prepare well-ordered films. Thereafter, the charge on gibbsite was reversed by dipping the film in pH 12 water to induce an ionic interaction between CNFs and gibbsite, enhancing the film properties; modulus improved from 9 GPa to 12 GPa, with a maintained strain-at-break of 6 % and tensile strength of 190 MPa. Additionally, the charge-reversed film swelled a factor of 24 less than a film without any gibbsite. At 23 °C and 80 % RH, the oxygen barrier properties were improved by a factor of 28, to a value of 18 ml·μm·m−2·kPa−1·24 h−1 and the water vapour barrier properties were improved by a factor of 12, to a value of 105 g·μm·m−2·kPa−1·24 h−1.
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