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- Ghaderi, M, et al.
(författare)
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Genome-wide transcriptome profiling of ex-vivo precision-cut slices from human pancreatic ductal adenocarcinoma
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 9070-
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Tidskriftsartikel (refereegranskat)abstract
- Ex-vivo tumor tissue culture systems are used as models to test specific anti-cancer drugs. Their main advantage is that they are closely comparable with the in vivo tumor in their host organism. We previously reported that precision-cut organotypic tissue slices of pancreatic ductal adenocarcinoma (PDAC) can be successfully cultured ex-vivo for at least 4 days. In order to study how culturing might affect transcription patterns, we now performed genome-wide transcriptome profiling of both baseline (0 h) and explanted tumors at daily intervals (24, 48 and 72 h) after start of culturing. The total-RNA from five samples of surgically resected human PDAC tumors at baseline and at different time points in culture was sequenced. Differential gene expression analysis of the whole transcriptome, testing 58,713 genes and over 206,000 transcripts, found that only a small number of genes showed significant changes in expression between baseline and cultured samples. The cultured tumor slices showed upregulation of a median of 12, 10 and 15 genes and downregulation of a median of 15, 12 and 25 genes at 24, 48 and 72 h in culture, respectively. One sample had morphologically increasing loss of tissue viability (range 0–18%). The vascular endothelial growth factor A (VEGFA) was significantly upregulated during the entire culture period in this case. Pathway over-representation analysis suggested that VEGFA together with the PTGS2 gene were upregulated at the same time as HIF-1-triggered cell apoptosis via NF-ĸB and the AP-1 activating factor was induced. Indeed, increased areas of apoptotic lesions were visible in this sample after 24 hours of culture. In conclusion, genome-wide transcriptome analysis supports that ex-vivo cultured tissue slices of PDAC may be a representative model of the original tumor. Transcriptome analysis was found to be a valuable complement to morphology for evaluation of ex-vivo cultures of PDAC.
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- Seidel, Maria, et al.
(författare)
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Study protocol of comprehensive risk evaluation for anorexia nervosa in twins (CREAT) : a study of discordant monozygotic twins with anorexia nervosa.
- 2020
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Ingår i: BMC Psychiatry. - : BioMed Central. - 1471-244X. ; 20:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Anorexia nervosa (AN) is a severe disorder, for which genetic evidence suggests psychiatric as well as metabolic origins. AN has high somatic and psychiatric comorbidities, broad impact on quality of life, and elevated mortality. Risk factor studies of AN have focused on differences between acutely ill and recovered individuals. Such comparisons often yield ambiguous conclusions, as alterations could reflect different effects depending on the comparison. Whereas differences found in acutely ill patients could reflect state effects that are due to acute starvation or acute disease-specific factors, they could also reflect underlying traits. Observations in recovered individuals could reflect either an underlying trait or a "scar" due to lasting effects of sustained undernutrition and illness. The co-twin control design (i.e., monozygotic [MZ] twins who are discordant for AN and MZ concordant control twin pairs) affords at least partial disambiguation of these effects.METHODS: Comprehensive Risk Evaluation for Anorexia nervosa in Twins (CREAT) will be the largest and most comprehensive investigation of twins who are discordant for AN to date. CREAT utilizes a co-twin control design that includes endocrinological, neurocognitive, neuroimaging, genomic, and multi-omic approaches coupled with an experimental component that explores the impact of an overnight fast on most measured parameters.DISCUSSION: The multimodal longitudinal twin assessment of the CREAT study will help to disambiguate state, trait, and "scar" effects, and thereby enable a deeper understanding of the contribution of genetics, epigenetics, cognitive functions, brain structure and function, metabolism, endocrinology, microbiology, and immunology to the etiology and maintenance of AN.
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- Silva, M. F., et al.
(författare)
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Magnesium fluoride as low-refractive index material for near-ultraviolet filters applied to optical sensors
- 2020
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Ingår i: Vacuum. - : Elsevier BV. - 0042-207X. ; 181
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Tidskriftsartikel (refereegranskat)abstract
- This article describes the fabrication of MgF2 and MgO thin-film-based optical filters and compares the optical transmission of the filters over UV. The MgF2 thin-films were deposited by use of an e-beam technique and their optical properties were characterised by ellipsometry. The effect of substrate temperature on the optical properties was studied. The MgF2 optimum refractive indices were obtained with a substrate temperature between 200 °C and 300 °C. Optical simulations were performed to compare the performance of MgF2 and MgO in the fabrication of near-UV narrow bandpass optical filters. While MgO-based optical filters result in a higher transmittance peak intensity, especially at 350 nm, the MgF2 optical filters are narrower, present lower values of FWHM, a mean value of 20 nm. This feature could be especially relevant for specific applications on fluorescent optical sensors. Finally, a Fabry-Perot based on a MgF2/TiO2 optical filter was deposited, using an e-beam technique for the MgF2 thin-films and RF-sputtering technique for the TiO2 thin-films. The MgF2/TiO2 optical filter peak transmittance is approximately 70% close to 400 nm, as expected. The results are discussed with focus on applications in fluorescent optical sensors for peaks at 350, 370, 380 and 400 nm, respectively.
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| 7. |
- Ghaderi, A, et al.
(författare)
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ROR1 Is Expressed in Diffuse Large B-Cell Lymphoma (DLBCL) and a Small Molecule Inhibitor of ROR1 (KAN0441571C) Induced Apoptosis of Lymphoma Cells
- 2020
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Ingår i: Biomedicines. - : MDPI AG. - 2227-9059. ; 8:6
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Tidskriftsartikel (refereegranskat)abstract
- The receptor tyrosine kinase ROR1 is absent in most normal adult tissues, but overexpressed in several malignancies. In this study, we explored clinical and functional inhibitory aspects of ROR1 in diffuse large B-cell lymphoma (DLBCL). ROR1 expression in tumor cells was more often observed in primary refractory DLBCL, Richter’s syndrome and transformed follicular lymphoma than in relapsed and non-relapsed DLBCL patients (p < 0.001). A survival effect of ROR1 expression was preliminarily observed in relapsed/refractory patients independent of gender and stage but not of age, cell of origin and international prognostic index. A second generation small molecule ROR1 inhibitor (KAN0441571C) induced apoptosis of ROR1+ DLBCL cell lines, similar to venetoclax (BCL-2 inhibitor) but superior to ibrutinib (BTK inhibitor). The combination of KAN0441571C and venetoclax at EC50 concentrations induced almost complete killing of DLBCL cell lines. Apoptosis was accompanied by the downregulation of BCL-2 and MCL-1 and confirmed by the cleavage of PARP and caspases 3, 8, 9. PI3Kδ/AKT/mTOR (non-canonical Wnt pathway) as well as β-catenin and CK1δ (canonical pathway) were inactivated. In zebra fishes transplanted with a ROR1+ DLBCL cell line, KAN0441571C induced a significant tumor reduction. New drugs with mechanisms of action other than those available for DLBCL are warranted. ROR1 inhibitors might represent a novel promising approach.
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| 8. |
- Ghaderi, Mohammadamir, 1986, et al.
(författare)
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Self-Cleaning Micro-Windows for In-Tailpipe Optical Exhaust Gas Measurements
- 2020
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Ingår i: IEEE International Symposium on Industrial Electronics. ; , s. 1104-1108
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Konferensbidrag (refereegranskat)abstract
- Exhaust gas measurement in the harsh environment of the tailpipe of a combustion engine by optical techniques is a highly robust technique, provided that optical access is maintained in the presence of particulate matter (PM). The considerations are presented for the systematic design of membranes with integrated heaters in SiC-on-Si technology for generating a well-defined lateral temperature profile with peak temperatures above 600 °C. Periodically raising the temperature of the membranes to such a level is demonstrated to keep the surface transparent by oxidation of soot deposits. This paper is about continuous heating of the membrane to a temperature slightly higher than that of the exhaust gas. At such temperatures thermophoretic repulsion of PM allows allows long-term optical measurement in the exhaust without the thermo-mechanical loading by repetitive thermal cycling.
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| 9. |
- Ghaderi, Mohammadamir, 1986, et al.
(författare)
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Thermally regenerable optical transparent MEMS windows for exhaust gas analysis
- 2020
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Ingår i: Optics InfoBase Conference Papers.
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Konferensbidrag (refereegranskat)abstract
- Exhaust gas measurement in the harsh environment of the tailpipe by optical techniques is a highly robust technique, provided that optical access is maintained in the presence of soot. The design, fabrication, and testing of membranes in SiC-on-Si with integrated heaters to serve as a regenerable MEMS optical window into the tailpipe are presented. Membranes at slightly elevated temperatures are demonstrated to keep the surface transparent by thermophoresis, while surface regeneration is achieved at pulsed high temperatures, which allows long-term optical measurement in the exhaust.
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- Middelburg, Luke M., et al.
(författare)
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Exploring the response of a resistive soot sensor to AC electric excitation
- 2020
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Ingår i: Journal of Aerosol Science. - : Elsevier BV. - 0021-8502 .- 1879-1964. ; 146
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Tidskriftsartikel (refereegranskat)abstract
- The resistive particulate matter sensor is a simple device that transduces the presence of soot through impedance change across inter-digital electrodes (IDEs). We investigate the information provided by impedance spectroscopy over the frequency range from 100 Hz to 10 kHz for two purposes. The first is to investigate the opportunities for an improved sensor response to particulate matter (PM), based on the additional information provided by the measurement of both the in-phase (resistive) and out-of-phase (capacitive) components of the change in impedance over this frequency range as compared to DC resistance measurement only. Secondly, the origin of the capacitive response of the device is investigated from the perspective that soot on the device is in the form of bendable dendrites that grow in three dimensions. An IDE structure with the housing acting as an additional suspended electrode for introducing a controllable vertical electric field component has been used for this purpose. The formation of dipoles, due to bending of the charged dendrites, is found to be the source of the capacitive response. Simulation of electrostatic soot deposition reinforces dendritic self-assembly mechanisms, driven by charged particle trajectories along electric field lines. Optical microscopy confirms that dendrites growing out of the substrate plane are sensitive to electric and flow forces, bending when force balances are appropriate. We also apply impedance spectroscopy under varying electric field strengths, showing that capacitive response is only observed when conditions are conducive to dendrite bending in response to the applied AC electric fields.
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