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| 2. |
- In ’t Veld, Sjors G.J.G., et al.
(författare)
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Detection and localization of early- and late-stage cancers using platelet RNA
- 2022
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Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 40:9, s. 999-1009.e6
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Tidskriftsartikel (refereegranskat)abstract
- Cancer patients benefit from early tumor detection since treatment outcomes are more favorable for less advanced cancers. Platelets are involved in cancer progression and are considered a promising biosource for cancer detection, as they alter their RNA content upon local and systemic cues. We show that tumor-educated platelet (TEP) RNA-based blood tests enable the detection of 18 cancer types. With 99% specificity in asymptomatic controls, thromboSeq correctly detected the presence of cancer in two-thirds of 1,096 blood samples from stage I–IV cancer patients and in half of 352 stage I–III tumors. Symptomatic controls, including inflammatory and cardiovascular diseases, and benign tumors had increased false-positive test results with an average specificity of 78%. Moreover, thromboSeq determined the tumor site of origin in five different tumor types correctly in over 80% of the cancer patients. These results highlight the potential properties of TEP-derived RNA panels to supplement current approaches for blood-based cancer screening.
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| 3. |
- Balossino, I., et al.
(författare)
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U-Rania : A neutron detector based on μ-rwell technology
- 2020
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Ingår i: Journal of Instrumentation. - 1748-0221. ; 15:9
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Tidskriftsartikel (refereegranskat)abstract
- In the framework of the ATTRACT-uRANIA project, funded by the European Community, we are developing an innovative neutron imaging detector based on micro-Resistive WELL (μ-RWELL) technology. The μ-RWELL, based on the resistive detector concept, ensuring an efficient spark quenching mechanism, is a highly reliable device. It is composed by two main elements: A readout-PCB and a cathode. The amplification stage for this device is embedded in the readout board through a resistive layer realized by means of an industrial process with DLC (Diamond-Like Carbon). A thin layer of \boro on the copper surface of the catode allows the thermal neutrons detection through the release of \litio and α particles in the active volume. This technology has been developed to be an efficient and convenient alternative to the 3He shortage. The goal of the project is to prove the feasibility of such a novel neutron detector by developing and testing small planar prototypes with readout boards suitably segmented with strip or pad readout, equipped with existing electronics or readout in current mode. Preliminary results from the test with different prototypes, showing a good agreement with the simulation, will be presented together with construction details of the prototypes and the future steps of the project.
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| 4. |
- Kidiyoor, GR, et al.
(författare)
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ATR is essential for preservation of cell mechanics and nuclear integrity during interstitial migration
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 4828-
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Tidskriftsartikel (refereegranskat)abstract
- ATR responds to mechanical stress at the nuclear envelope and mediates envelope-associated repair of aberrant topological DNA states. By combining microscopy, electron microscopic analysis, biophysical and in vivo models, we report that ATR-defective cells exhibit altered nuclear plasticity and YAP delocalization. When subjected to mechanical stress or undergoing interstitial migration, ATR-defective nuclei collapse accumulating nuclear envelope ruptures and perinuclear cGAS, which indicate loss of nuclear envelope integrity, and aberrant perinuclear chromatin status. ATR-defective cells also are defective in neuronal migration during development and in metastatic dissemination from circulating tumor cells. Our findings indicate that ATR ensures mechanical coupling of the cytoskeleton to the nuclear envelope and accompanying regulation of envelope-chromosome association. Thus the repertoire of ATR-regulated biological processes extends well beyond its canonical role in triggering biochemical implementation of the DNA damage response.
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| 5. |
- Firuzi, O, et al.
(författare)
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Role of c-MET Inhibitors in Overcoming Drug Resistance in Spheroid Models of Primary Human Pancreatic Cancer and Stellate Cells
- 2019
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Ingår i: Cancers. - : MDPI AG. - 2072-6694. ; 11:5
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Tidskriftsartikel (refereegranskat)abstract
- Pancreatic stellate cells (PSCs) are a key component of tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC) and contribute to drug resistance. c-MET receptor tyrosine kinase activation plays an important role in tumorigenesis in different cancers including PDAC. In this study, effects of PSC conditioned medium (PCM) on c-MET phosphorylation (by immunocytochemistry enzyme-linked immunosorbent assay (ELISA)) and drug response (by sulforhodamine B assay) were investigated in five primary PDAC cells. In novel 3D-spheroid co-cultures of cyan fluorescence protein (CFP)-firefly luciferase (Fluc)-expressing primary human PDAC cells and green fluorescence protein (GFP)-expressing immortalized PSCs, PDAC cell growth and chemosensitivity were examined by luciferase assay, while spheroids’ architecture was evaluated by confocal microscopy. The highest phospho-c-MET expression was detected in PDAC5 and its subclone sorted for “stage specific embryonic antigen-4” (PDAC5 (SSEA4)). PCM of cells pre-incubated with PDAC conditioned medium, containing increased hepatocyte growth factor (HGF) levels, made PDAC cells significantly more resistant to gemcitabine, but not to c-MET inhibitors. Hetero-spheroids containing both PSCs and PDAC5 (SSEA4) cells were more resistant to gemcitabine compared to PDAC5 (SSEA4) homo-spheroids. However, c-MET inhibitors (tivantinib, PHA-665752 and crizotinib) were equally effective in both spheroid models. Experiments with primary human PSCs confirmed the main findings. In conclusion, we developed spheroid models to evaluate PSC–PDAC reciprocal interaction, unraveling c-MET inhibition as an important therapeutic option against drug resistant PDAC.
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| 6. |
- Banks, J., et al.
(författare)
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Assessment of Digital Image Correlation as a method of obtaining deformations of a structure under fluid load
- 2015
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Ingår i: Journal of Fluids and Structures. - : Academic Press. - 0889-9746 .- 1095-8622. ; 58, s. 173-187
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Tidskriftsartikel (refereegranskat)abstract
- Digital Image Correlation (DIC) is employed for the measurement of full-field deformation during fluid-structure interaction experiments in a wind tunnel. The methodology developed for the wind tunnel environment is quantitatively assessed. The static deformation error of the system is shown to be less than 0.8% when applied to a curved aerofoil specimen moved through known displacements using a micrometre. Enclosed camera fairings were shown to be required to minimise error due to wind induced camera vibration under aerodynamic loading. The methodology was demonstrated using a high performance curved foil, from a NACRA F20 sailing catamaran, tested within the University of Southampton RJ Mitchell, 3.5. mx2.4. m, wind tunnel. The aerodynamic forces induced in the wind tunnel are relatively small, compared with typical hydrodynamic loading, resulting in small deformations. The coupled deflection and blade twist is evaluated over the tip region (80-100% Span, measured from the root) for a range of wind speeds and angles of attack. Steady deformations at low angles of attack were shown to be well captured however unsteady deformations at higher angles of attack were observed as an increase in variability due to hardware limitations in the current DIC system. It is concluded that higher DIC sample rates are required to assess unsteady deformations in the future. The full field deformation data reveals limited blade twist for low angles of attack, below the stall angle. For larger angles, however, there is a tendency to reduce the effective angle of attack at the tip of the structure, combined with an unsteady structural response. This capability highlights the benefits of the presented methodology over fixed-point measurements as the three dimensional foil deflections can be assessed over a large tip region. In addition, the methodology demonstrates that very small deformations and twist angles can be resolved.
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| 7. |
- Best, Myron G., et al.
(författare)
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Swarm Intelligence-Enhanced Detection of Non-Small-Cell Lung Cancer Using Tumor-Educated Platelets
- 2017
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Ingår i: Cancer Cell. - : Elsevier. - 1535-6108 .- 1878-3686. ; 32:2, s. 238-252
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Tidskriftsartikel (refereegranskat)abstract
- Blood-based liquid biopsies, including tumor-educated blood platelets (TEPs), have emerged as promising biomarker sources for non-invasive detection of cancer. Here we demonstrate that particle-swarm optimization (PSO)-enhanced algorithms enable efficient selection of RNA biomarker panels from platelet RNA sequencing libraries (n = 779). This resulted in accurate TEP-based detection of early- and late-stage non-small-cell lung cancer (n = 518 late-stage validation cohort, accuracy, 88%; AUC, 0.94; 95% CI, 0.92-0.96; p < 0.001; n = 106 early-stage validation cohort, accuracy, 81%; AUC, 0.89; 95% CI, 0.83-0.95; p < 0.001), independent of age of the individuals, smoking habits, whole-blood storage time, and various inflammatory conditions. PSO enabled selection of gene panels to diagnose cancer from TEPs, suggesting that swarm intelligence may also benefit the optimization of diagnostics readout of other liquid biopsy biosources.
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| 8. |
- Håkanson, Cecilia, et al.
(författare)
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Place of death of children with complex chronic conditions : cross-national study of 11 countries.
- 2017
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Ingår i: European Journal of Pediatrics. - : Springer Science and Business Media LLC. - 0340-6199 .- 1432-1076. ; 176:3, s. 327-335
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Tidskriftsartikel (refereegranskat)abstract
- Cross-national understanding of place of death is crucial for health service systems for their provision of efficient and equal access to paediatric palliative care. The objectives of this population-level study were to examine where children with complex chronic conditions (CCC) die and to investigate associations between places of death and sex, cause of death and country. The study used death certificate data of all deceased 1- to 17-year-old children (n = 40,624) who died in 2008, in 11 European and non-European countries. Multivariable logistic regression was performed to determine associations between place of death and other factors. Between 24.4 and 75.3% of all children 1-17 years in the countries died of CCC. Of these, between 6.7 and 42.4% died at home. In Belgium and the USA, all deaths caused by CCC other than malignancies were less likely to occur at home, whereas in Mexico and South Korea, deaths caused by neuromuscular diseases were more likely to occur at home than malignancies. In Mexico (OR = 0.91, 95% CI: 0.83-1.00) and Sweden (OR = 0.35, 95% CI: 0.15-0.83), girls had a significantly lower chance of dying at home than boys.CONCLUSION: This study shows large cross-national variations in place of death. These variations may relate to health system-related infrastructures and policies, and differences in cultural values related to place of death, although this needs further investigation. The patterns found in this study can inform the development of paediatric palliative care programs internationally. What is known: • There is a scarcity of population-level studies investigating where children with CCC die in different countries. • Cross-national understanding of place of death provides information to health care systems for providing efficient and equal access to paediatric palliative care. What is new : • There are large cross-national variations in the place of death of children with CCC, with few deathsoccuring at home in some countries whereas hospital deaths are generally most common. • In general, deaths caused by neuromuscular diseases and malignancies occur at home more often thanother CCC.
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| 9. |
- Lanata, N., et al.
(författare)
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Orbital selectivity in Hund's metals: The iron chalcogenides
- 2013
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Ingår i: Physical Review B. - : American Physical Society. - 1098-0121 .- 1550-235X. ; 87:4
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Tidskriftsartikel (refereegranskat)abstract
- We show that electron correlations lead to a bad metallic state in chalcogenides FeSe and FeTe despite the intermediate value of the Hubbard repulsion U and Hund’s rule coupling J. The evolution of the quasi particle weight Z as a function of the interaction terms reveals a clear crossover at U ≃ 2.5 eV. In the weak coupling limit Z decreases for all correlated d orbitals as a function of U and beyond the crossover coupling they become weakly dependent on U while strongly depend on J. A marked orbital dependence of the Z’s emerges even if in general the orbital-selective Mott transition only occurs for relatively large values of U. This two-stage reduction of the quasi particle coherence due to the combined effect of Hubbard U and the Hund’s J, suggests that the iron-based superconductors can be referred to as Hund’s correlated metals.
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| 10. |
- Marimon Giovannetti, Laura, et al.
(författare)
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Toward the development of a hydrofoil tailored to passively reduce its lift response to fluid load
- 2018
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Ingår i: Ocean Engineering. - : Elsevier Ltd. - 0029-8018 .- 1873-5258. ; 167, s. 1-10
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this research is to explore the possibility of using Passive Adaptive Composite (PAC) on structures to help control the lift generated by hydrofoils on boats such as the International Moth. Introducing composite fibres oriented at off-principal axis angles, allow a foil to passively control its pitch angle to reduce the lift generated at higher boat speeds helping to achieve a stable flight in a wide range of weather conditions. PAC utilises the inherent flexibility of a composite structure to induce a twist response under bending load which could be used to minimise the use of active control systems, or even improve the dynamic response of foils in waves. However, to design flexible foils requires numerical and experimental tools to assess the complex fluid structure interactions involved. This paper evaluates a simplified hydrofoil geometry designed to reduce its lift coefficient with increased flow speed. A coupled Computational Fluid Dynamics (CFD) and Finite Element Analysis (FEA) methodology is presented to predict flexible foil performance. Validation of these numerical tools is achieved through the use of wind tunnel experiments including full field deformation measurements. Twist deformations resulted in a reduction in the effective angle of attack by approximately 30% at higher flow speeds reducing the foil lift and drag significantly
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