| 21. |
- Kehoe, Laura, et al.
(författare)
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Make EU trade with Brazil sustainable
- 2019
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Ingår i: Science. - : American Association for the Advancement of Science (AAAS). - 0036-8075 .- 1095-9203. ; 364:6438, s. 341-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 22. |
- Kennedy, Patrick J., et al.
(författare)
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Fab-conjugated PLGA nanoparticles effectively target cancer cells expressing human CD44v6
- 2018
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Ingår i: Acta Biomaterialia. - : Elsevier BV. - 1742-7061 .- 1878-7568. ; 81, s. 208-218
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Tidskriftsartikel (refereegranskat)abstract
- Targeting of CD44 isoforms containing exon v6 (CD44v6) represents a viable strategy for the therapy and/or early diagnosis of metastatic cancers of the epithelium (e.g. gastric and colorectal cancer). We developed and characterized poly(lactic-co-glycolic acid) (PLGA)-based nanoparticles (NPs) modified with polyethylene glycol (PEG) and engrafted, by site-directed conjugation, with an engineered human Fab that specifically target human CD44v6 (v6 Fab-PLGA NPs). The v6 Fab-PLGA NPs displayed spherical morphology around 300 nm and were negatively charged. They strongly bound to a CD44v6-derived peptide and, more importantly, to cells that endogenously and exogenously express CD44v6, but not to non expressing cells and cells expressing the standard isoform of CD44. The v6 Fab-PLGA NPs also recognized CD44v6 in tumor sections from cells grown subcutaneously within mice. The NPs had nominal cytotoxicity at 50 mu g/mL and withstood simulated intestinal fluid exposure. Interestingly, v6 Fab-PLGA NPs cryopreserved in 10% trehalose and stored maintained specific cell binding. In conclusion, we envision NPs targeting CD44v6 as potential in vivo diagnostic agents and/or as anti-cancer agents in patients previously stratified with CD44v6(+) carcinomas. Statement of Significance The v6 Fab-PLGA NPs displayed many favorable qualities as a potential CD44v6-targeted drug and/or diagnostic delivery agent. The NPs were designed for optimal ligand orientation and for immediate administration into humans. v6 Fab-PLGA NPs strongly bound to cells that endogenously and exogenously express CD44v6, but not to non-expressing cells and cells expressing the standard isoform of CD44. Binding ability was retained after freeze-drying and long-term storage, providing evidences on the stability of Fab-functionalized NPs. These NPs can potentially be used as an in vivo diagnostic from parenteral or oral/rectal administration.
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| 23. |
- Kennedy, Patrick J., et al.
(författare)
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Impact of surfactants on the target recognition of Fab-conjugated PLGA nanoparticles
- 2018
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Ingår i: European journal of pharmaceutics and biopharmaceutics. - : Elsevier. - 0939-6411 .- 1873-3441. ; 127, s. 366-370
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Tidskriftsartikel (refereegranskat)abstract
- Targeted drug delivery with nanoparticles (NPs) requires proper surface ligand presentation and availability. Surfactants are often used as stabilizers in the production of targeted NPs. Here, we evaluated the impact of surfactants on ligand functionalization and downstream molecular recognition. Our model system consisted of fluorescent poly(lactic-co-glycolic acid) (PLGA) NPs that were nanoprecipitated in one of a small panel of commonly-used surfactants followed by equivalent washes and conjugation of an engineered Fab antibody fragment. Size, polydispersity index and zeta potential were determined by dynamic light scattering and laser Doppler anemometry, and Fab presence on the NPs was assessed by enzyme-linked immunosorbent assay. Most importantly, Fab-decorated NP binding to the cell surface receptor was monitored by fluorescence-activated cell sorting. 2% polyvinyl alcohol, 1% sodium cholate, 0.5% Pluronic F127 (F127) and 2% Tween-80 were initially tested. Of the four surfactants tested, PLGA NPs in 0.5% F127 and 2% Tween-80 had the highest cell binding. These two surfactants were then retested in two different concentrations, 0.5% and 2%. The Fab-decorated PLGA NPs in 2% F127 had the highest cell binding. This study highlights the impact of common surfactants and their concentrations on the downstream targeting of ligand-decorated NPs. Similar principles should be applied in the development of future targeted nanosystems where surfactants are employed.
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| 24. |
- Kobayashi, Masatake, et al.
(författare)
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Machine Learning-Derived Echocardiographic Phenotypes Predict Heart Failure Incidence in Asymptomatic Individuals
- 2022
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Ingår i: JACC: Cardiovascular Imaging. - : Elsevier BV. - 1876-7591 .- 1936-878X. ; 15:2, s. 193-208
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: This study sought to identify homogenous echocardiographic phenotypes in community-based cohorts and assess their association with outcomes.BACKGROUND: Asymptomatic cardiac dysfunction leads to a high risk of long-term cardiovascular morbidity and mortality; however, better echocardiographic classification of asymptomatic individuals remains a challenge.METHODS: Echocardiographic phenotypes were identified using K-means clustering in the first generation of the STANISLAS (Yearly non-invasive follow-up of Health status of Lorraine insured inhabitants) cohort (N = 827; mean age: 60 ± 5 years; men: 48%), and their associations with vascular function and circulating biomarkers were also assessed. These phenotypes were externally validated in the Malmö Preventive Project cohort (N = 1,394; mean age: 67 ± 6 years; men: 70%), and their associations with the composite of cardiovascular mortality (CVM) or heart failure hospitalization (HFH) were assessed as well.RESULTS: Three echocardiographic phenotypes were identified as "mostly normal (MN)" (n = 334), "diastolic changes (D)" (n = 323), and "diastolic changes with structural remodeling (D/S)" (n = 170). The D and D/S phenotypes had similar ages, body mass indices, cardiovascular risk factors, vascular impairments, and diastolic function changes. The D phenotype consisted mainly of women and featured increased levels of inflammatory biomarkers, whereas the D/S phenotype, consisted predominantly of men, displayed the highest values of left ventricular mass, volume, and remodeling biomarkers. The phenotypes were predicted based on a simple algorithm including e', left ventricular mass and volume (e'VM algorithm). In the Malmö cohort, subgroups derived from e'VM algorithm were significantly associated with a higher risk of CVM and HFH (adjusted HR in the D phenotype = 1.87; 95% CI: 1.04 to 3.37; adjusted HR in the D/S phenotype = 3.02; 95% CI: 1.71 to 5.34).CONCLUSIONS: Among asymptomatic, middle-aged individuals, echocardiographic data-driven classification based on the simple e'VM algorithm identified profiles with different long-term HF risk. (4th Visit at 17 Years of Cohort STANISLAS-Stanislas Ancillary Study ESCIF [STANISLASV4]; NCT01391442).
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| 25. |
- Lindgård, Jan, et al.
(författare)
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Nordic Europe
- 2017
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Ingår i: Alkali-aggregate reaction in concrete. - : Taylor & Francis. - 9781315708959 - 9781138027565 ; , s. 277-320, s. 185-211
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 26. |
- Livingston, John H, et al.
(författare)
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Leukoencephalopathy with Calcifications and Cysts : A Purely Neurological Disorder Distinct from Coats Plus
- 2014
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Ingår i: Neuropediatrics. - : Georg Thieme Verlag KG. - 0174-304X .- 1439-1899. ; 45:3, s. 175-182
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Tidskriftsartikel (refereegranskat)abstract
- Objective With the identification of mutations in the conserved telomere maintenance component 1 (CTC1) gene as the cause of Coats plus (CP) disease, it has become evident that leukoencephalopathy with calcifications and cysts (LCC) is a distinct genetic entity. Patients and Methods A total of 15 patients with LCC were identified from our database of patients with intracranial calcification. The clinical and radiological features are described. Results The median age (range) at presentation was 10 months (range, 2 days-54 years). Of the 15 patients, 9 presented with epileptic seizures, 5 with motor abnormalities, and 1 with developmental delay. Motor abnormalities developed in 14 patients and cognitive problems in 13 patients. Dense calcification occurred in the basal ganglia, thalami, dentate nucleus, brain stem, deep gyri, deep white matter, and in a pericystic distribution. Diffuse leukoencephalopathy was present in all patients, and it was usually symmetrical involving periventricular, deep, and sometimes subcortical, regions. Cysts developed in the basal ganglia, thalamus, deep white matter, cerebellum, or brain stem. In unaffected areas, normal myelination was present. No patient demonstrated cerebral atrophy. Conclusion LCC shares the neuroradiological features of CP. However, LCC is a purely neurological disorder distinguished genetically by the absence of mutations in CTC1. The molecular cause(s) of LCC has (have) not yet been determined.
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| 27. |
- Monzo, Luca, et al.
(författare)
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Visit-to-visit blood pressure variation and outcomes in heart failure with reduced ejection fraction: findings from the Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms trial.
- 2020
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Ingår i: Journal of hypertension. - 1473-5598. ; 38:3, s. 420-425
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Tidskriftsartikel (refereegranskat)abstract
- Visit-to-visit office blood pressure (BP) variability (BPV) has been associated with morbidity and mortality outcomes in several cardiovascular conditions. The aim of this study was to evaluate the association between BPV and outcomes in patients with heart failure and reduced ejection fraction and the effect of eplerenone on BPV.We evaluated the associations between BPV, calculated as SBP coefficient of variation (SBP-CoV = SD/mean × 100%), and the primary composite endpoint of cardiovascular mortality or heart failure hospitalization (HFH), and its components, in 2549 patients from the Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms trial. Lower SBP-CoV was independently associated with a higher risk of all the studied outcomes, while higher as well as lower SBP-CoV were associated with a higher risk of cardiovascular death. After a median follow-up period of 21 months the risk of the composite outcome of cardiovascular death or HFH was almost double in the lower SBP-CoV tertile as compared with the intermediate tertile [adjusted hazard ratio: 2.01, 95% confidence interval (1.62-2.51), P < 0.001]. The relationship between SBP-CoV and outcomes was not modified by eplerenone (P value for interaction = 0.48). An interaction was detected between mean SBP and SBP-CoV for the primary outcome (P = 0.048) and for HFH (P = 0.018). The effect modification was slight, but lower SBP-CoV was associated with worse outcomes in patients with both low and high SBP, while this interaction was less clear for patients with SBP in the 'normal' range.In our patients with heart failure and reduced ejection fraction and mild symptoms, both a lower and higher SBP-CoV were associated with worse outcomes. SBP-CoV did not modify the benefit of eplerenone. Further studies are warranted to clarify the role of BPV in heart failure. CLINICALTRIALS.NCT00232180.
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| 28. |
- Rich, Rebecca L., et al.
(författare)
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A global benchmark study using affinity-based biosensors
- 2009
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Ingår i: Analytical Biochemistry. - : Elsevier BV. - 0003-2697 .- 1096-0309. ; 386:2, s. 194-216
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Tidskriftsartikel (refereegranskat)abstract
- To explore the variability in biosensor studies, 150 participants from 20 countries were given the same protein samples and asked to determine kinetic rate constants for the interaction. We chose a protein system that was amenable to analysis using different biosensor platforms as well as by users of different expertise levels. The two proteins (a 50-kDa Fab and a 60-kDa glutathione S-transferase [GST] antigen) form a relatively high-affinity complex, so participants needed to optimize several experimental parameters, including ligand immobilization and regeneration conditions as well as analyte concentrations and injection/dissociation times. Although most participants collected binding responses that could be fit to yield kinetic parameters, the quality of a few data sets could have been improved by optimizing the assay design. Once these outliers were removed, the average reported affinity across the remaining panel of participants was 620 pM with a standard deviation of 980 pM. These results demonstrate that when this biosensor assay was designed and executed appropriately, the reported rate constants were consistent, and independent of which protein was immobilized and which biosensor was used.
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| 29. |
- Rowland, Lucy, et al.
(författare)
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Shock and stabilisation following long-term drought in tropical forest from 15 years of litterfall dynamics
- 2018
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Ingår i: Journal of Ecology. - : Wiley. - 0022-0477 .- 1365-2745. ; 106:4, s. 1673-1682
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Tidskriftsartikel (refereegranskat)abstract
- Litterfall dynamics in tropical forests are a good indicator of overall tropical forest function, indicative of carbon invested in both photosynthesising tissues and reproductive organs such as flowers and fruits. These dynamics are sensitive to changes in climate, such as drought, but little is known about the long-term responses of tropical forest litterfall dynamics to extended drought stress. We present a 15-year dataset of litterfall (leaf, flower and fruit, and twigs) from the world's only long-running drought experiment in tropical forest. This dataset comprises one of the longest published litterfall time series in natural forest, which allows the long-term effects of drought on forest reproduction and canopy investment to be explored. Over the first 4 years of the experiment, the experimental soil moisture deficit created only a small decline in total litterfall and leaf fall (12% and 13%, respectively), but a very strong initial decline in reproductive litterfall (flowers and fruits) of 54%. This loss of flowering and fruiting was accompanied by a de-coupling of all litterfall patterns from seasonal climate variables. However, following >10 years of the experimental drought, flower and fruiting re-stabilised at levels greater than in the control plot, despite high tree mortality in the drought plot. Litterfall relationships with atmospheric drivers were re-established alongside a strong new apparent trade-off between litterfall and tree growth. Synthesis. We demonstrate that this tropical forest went through an initial shock response during the first 4 years of intense drought, where reproductive effort was arrested and seasonal litterfall patterns were lost. However, following >10 years of experimental drought, this system appears to be re-stabilising at a new functional state where reproduction is substantially elevated on a per tree basis; and there is a new strong trade-off between investment in canopy production and wood production.
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| 30. |
- Souza De Almeida, J., et al.
(författare)
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Optical properties of donor-triad cluster in GaAs and GaN
- 2002
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Ingår i: Applied Physics Letters. - : AIP Publishing. - 0003-6951 .- 1077-3118. ; 81:17, s. 3158-3160
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Tidskriftsartikel (refereegranskat)abstract
- The effect of the transition energy of three-donor clusters on far infrared absorption in n-type semiconductor materials has been investigated by a multiconfigurational self-consistent-field model calculation and applied to GaAs and GaN systems. We show that it is crucial to consider the many-particle correlation effects within three-donor clusters. With electron correlation taken into account, the present results support the interpretation of a very recent unidentified peak energy observed in absorption measurement of GaN as due to electronic transitions in these clusters. We also corroborate the suggestion that the X line in GaAs arises from such transitions.
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